PMID- 1373478
TI  - T-cell receptor germline genes and multiple sclerosis susceptibility: an
      unfinished tale.

PMID- 1373479
TI  - Rupture of ectopic pregnancy following disappearance of serum beta subunit of
      hCG.
AB  - The introduction of sensitive assays for the beta subunit of hCG (beta-hCG) and
      improved ultrasound technology for diagnosis and monitoring of ectopic pregnancy
      have changed the clinical approach to the management of ectopic pregnancy. Only a
      few reports have been published of patients with ectopic gestation and negative
      serum beta-hCG levels. None of these described rupture of ectopic pregnancy
      following the decline of beta-hCG levels to below 10 mIU/mL. We describe a case
      of ectopic pregnancy, managed expectantly, in which rupture and hemoperitoneum
      occurred after the decline of beta-hCG levels to below 10 mIU/mL.

PMID- 1373480
TI  - Hypervolemic pulmonary edema and severe coagulopathy after intrauterine dextran
      instillation.
AB  - A healthy young woman with recurrent spontaneous abortion and septate uterus
      underwent hysteroscopic metroplasty with intracavitary instillation of 1350 mL of
      10% dextran 40 in normal saline. After the operation, the patient developed acute
      hypervolemic pulmonary edema and severe coagulopathy due to temporary impairment
      of platelet function. Fluid overload, which could have been caused by the
      hyperosmolar properties of dextran, worsened progressively as fluids were drawn
      from the interstitial space and urine output was reduced. The use of a dilute
      and/or low-molecular-weight dextran solution to distend the uterine cavity during
      operative hysteroscopy is not without risk of complications.

PMID- 1373481
TI  - Rate of vascularization of coralline hydroxyapatite ocular implants.
AB  - Twelve patients received a coralline hydroxyapatite sphere as a buried integrated
      ocular implant after enucleation surgery. The implant was modified by drilling 5
      access holes, 1 mm in diameter, to the center of the sphere to allow more rapid
      host tissue ingrowth. 99Tc MDP static and dynamic bone scan studies were
      performed at various intervals after implantation to confirm the time course for
      vascularization. Complete vascularization was noted in 1 of 2 patients at 8 weeks
      after surgery, in 7 of 7 patients at 10 to 12 weeks, and in 3 of 3 patients at 16
      weeks. This modified technique allows the hydroxyapatite ocular implants to be
      drilled for the final motility peg at an earlier time than currently possible,
      thereby resulting in more rapid cosmetic rehabilitation and obviating the need
      for secondary modification or replacement of the prosthesis.

PMID- 1373482
TI  - Genomic organization of the human c-kit gene: evolution of the receptor tyrosine
      kinase subclass III.
AB  - The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor. It
      belongs to receptor tyrosine kinase subclass III, which also includes the colony
      stimulating factor I receptor (c-fms), platelet-derived growth factor receptors A
      and B (PDGFRA and PDGFRB), as well as FLT1 and FLT3/FLK2. c-kit and PDGFRA, c-fms
      and PDGFRB, FLT1 and FLT3/FLK2 are grouped by pair in three clusters in man on
      chromosome 4 band q11-q13, chromosome 5 band q31-q33 and chromosome 13 band q12
      respectively. Here, we report the genomic organization of the human c-kit gene,
      which is composed of 21 small coding exons, distributed over 80 kb. Comparison of
      the c-kit and c-fms oncogenes shows that they share identified exon/intron
      boundaries in their two kinase domains, as well as a similar exon/intron
      organization in the extracytoplasmic domain. Comparison with the kinase domains
      of tyrosine kinase genes not belonging to subclass III suggests that the
      exon/intron organization of c-kit and c-fms is a characteristic feature of
      subclass III. The genomic similarities between c-kit and c-fms, in conjunction
      with the location in pairs on different chromosomes of the subclass III genes,
      has led us to hypothesize that cis and trans duplications gave rise to this group
      of genes.

PMID- 1373483
TI  - Lipopolysaccharide- and interferon-gamma-induced expression of hck and lyn
      tyrosine kinases in murine bone marrow-derived macrophages.
AB  - We have examined the role of tyrosine phosphorylation during the course of
      macrophage activation. Initial experiments indicated that vanadate, a known
      phosphotyrosine phosphatase inhibitor, enhanced the phorbol 12-myristate 13
      acetate (PMA)-triggered respiratory burst and potentiated the priming effects of
      bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), suggesting
      that tyrosine phosphorylation may be important in these end cell functions. As
      src-related kinases have been implicated in the activation of cells of other
      haemopoietic lineages, we examined the relationship between the activity of two
      such kinases, hck and lyn, and priming of the respiratory burst. We found that
      the level of hck and lyn is increased following exposure of bone marrow-derived
      macrophages (BMM) to LPS or IFN-gamma. The induction of both of these kinases
      follows similar kinetics with maximal activity occurring at 24-48 h.
      Interestingly, the kinetics of induction of hck and lyn kinase activity in BMM
      demonstrated a close temporal relationship with the priming effects of LPS and
      IFN-gamma on the macrophage respiratory burst. Collectively, these observations
      raise the possibility that modulation of expression of hck and lyn is involved in
      the regulation of the respiratory burst.

PMID- 1373484
TI  - Identification of distinct populations of PI-3 kinase activity following T-cell
      activation.
AB  - Activation of mature CD4+ T lymphocytes by antigen-presenting cells involves
      engagement of the CD3/T-cell antigen receptor complex along with the CD4 surface
      glycoprotein and the phosphorylation of cellular proteins on tyrosine residues
      leading to stimulation of a variety of cellular second-messenger systems. Several
      recent studies have implicated non-receptor protein tyrosine kinase of the src
      family, especially p56lck and p59fyn, in mediating at least a portion of these
      tyrosine phosphorylation events. In the present study we have examined the
      involvement of one type of second-messenger system, phosphatidylinositol-3 kinase
      (PI-3 kinase), in signal transduction during antibody-induced activation of
      normal resting human CD4+ T cells. We demonstrate that PI-3 kinase activity is
      increased following co-approximation of CD4 with the T-cell receptor and that PI
      3 kinase activity co-precipitates with the CD4-p56lck complex. We also show that
      following T-cell activation a complex containing PI-3 kinase activity can be
      demonstrated in CD3 epsilon immunoprecipitates which is distinct from that which
      interacts with p56lck.

PMID- 1373485
TI  - [The efficacy of therapy using 89Sr-strontium chloride in 200 patients with bone
      metastases of a prostatic cancer].
AB  - Since 1976 200 patients with multiple skeletal metastases from prostatic cancer
      were treated with 89Sr. In the present study the results were evaluated in order
      to confirm the efficacy of this therapy. Following the application of 3
      injections each of 0 (n = 21), 37 (n = 65), 75 (n = 72), 100 (n = 25) or 150 (n =
      17) MBq 89Sr subjective pain relief, scintigraphic follow-up observations,
      survival times and haematological complications were recorded. In comparison to
      the results of placebo administration the effects of 89Sr on pain were: in the
      placebo group deterioration 11%, no change 55%, improvement 17% and full pain
      relief 17% whereas in the Sr groups combined the corresponding figures were 3,
      38, 26 and 33%. Pain relief correlated with the activity administered. A dose
      relationship to scintigraphic regression is probable, the latter correlating with
      pain relief. Due to a decrease of early deaths the survival rate increased during
      the first months after start of treatment but later on returned to the level
      observed in untreated patients. Pain relief and regressive scintigraphic findings
      were combined with increased marrow involvement which, however, did not by itself
      influence survival rates. 89Sr therapy is an effective additional treatment of
      patients with multiple skeletal metastases from prostatic cancer.

PMID- 1373486
TI  - Isolation of the mitochondrial benzodiazepine receptor: association with the
      voltage-dependent anion channel and the adenine nucleotide carrier.
AB  - The mitochondrial benzodiazepine receptor (mBzR) has been solubilized with
      retention of reversible ligand binding, and the associated subunits were
      characterized. mBzR comprises immunologically distinct protein subunits of 18-,
      30-, and 32-kDa. The 18-kDa protein is labeled by the isoquinoline carboxamide
      mBzR ligand [3H]PK14105, whereas the 30- and 32-kDa subunits are labeled by the
      benzodiazepine (Bz) ligands [3H]flunitrazepam and [3H]AHN-086. Selective
      antibodies and reagents identify the 32- and 30-kDa proteins as the voltage
      dependent anion channel (VDAC) and the adenine nucleotide carrier (ADC),
      respectively. While isoquinoline carboxamide and Bz ligands target different
      subunits, they interact allosterically, as the binding of Bz and isoquinoline
      carboxamide ligands is mutually competitive at low nanomolar concentrations.
      Moreover, eosin-5-maleimide and mercuric chloride inhibit [3H]PK11195 binding to
      the intact receptor via sulfhydryl groups that are present in ADC. VDAC and ADC,
      outer and inner mitochondrial membrane channel proteins, respectively, together
      with the 18-kDa subunit, may comprise mBzR at functionally important transport
      sites at the junction of two mitochondrial membranes.

PMID- 1373488
TI  - Targeted cleavage of mRNA in vitro by RNase P from Escherichia coli.
AB  - External guide sequences (EGSs) complementary to mRNAs that encode beta
      galactosidase from Escherichia coli and nuclease A from Staphylococcus aureus can
      target these RNAs for cleavage in vitro by RNase P from E. coli. Specific
      cleavage occurs at locations predicted by the nucleotide sequences of the EGSs.
      EGSs with regions complementary to the mRNAs that are as short as 13 nucleotides
      function efficiently and turn over slowly during incubation with the target
      substrate and the enzyme. EGSs composed of deoxyribonucleotides as well as those
      composed of ribonucleotides are effective, but cleavage of the targeted substrate
      with DNA as an EGS is about 10-fold less efficient than that with RNA as an EGS.
      An RNA EGS inhibited the formation of beta-galactosidase activity in a crude
      extract (S30) of E. coli that was capable of catalyzing coupled transcription
      translation reactions.

PMID- 1373487
TI  - Human combinatorial antibody libraries to hepatitis B surface antigen.
AB  - Human antibody Fab fragments that bind to hepatitis B surface antigen (HBsAg)
      were generated by using a recombinant phage surface-display expression system.
      Characterization of HBsAg-specific Fab fragments isolated from two vaccinated
      individuals reveals diversity in specificity of antigen binding and in the
      sequences of the complementarity-determining region. The sequence results show
      examples of human light-chain promiscuity that result in fine specificity changes
      and a strong relationship to a human germ-line gene. This application illustrates
      further that this technique is a powerful tool to isolate distinct human
      antibodies against immunogenic viral targets.

PMID- 1373489
TI  - Interaction of immune sera with synthetic peptides corresponding to the
      structural protein region of hepatitis C virus.
AB  - Comparison of the deduced amino acid sequence from the structural region of the
      Hutchinson strain of hepatitis C virus (HCV-H) with four other HCV isolates
      clearly divides the five isolates into two groups based on sequence homology. The
      first group includes HCV-H, HCV-1, and HC-J1, while the second includes HCV-J1
      and HC-J4. Among the five isolates the first 190 residues (putative nucleocapsid)
      are highly conserved whereas residues 196-513 exhibit significant diversity and
      include a hypervariable region encompassing residues 386-404. A series of
      overlapping decapeptides were synthesized by solid-phase pin technology according
      to sequence from HCV-H (amino acids 1-513), HC-J4 (amino acids 181-513), and
      regions from the three other isolates which exhibited sequence variation. A
      modified ELISA was used to measure immunoreactivity of sera from clinical
      posttransfusion cases and experimentally infected chimpanzees. Comparison of pre-
      and postinfection samples revealed 16 clusters of immunoreactive peptides within
      the structural region, none of which was found in the hypervariable region. Only
      one cluster (amino acids 73-89) was recognized by all human and chimpanzee sera.
      Clear variation in the immune response was observed between individuals, although
      no obvious difference in reactivity between acute and chronic cases was observed.
      Within individual profiles, the reactivity to each peptide cluster and the total
      number of reactive clusters increased over time.

PMID- 1373491
TI  - Regulated expression of the calmodulin-related TCH genes in cultured Arabidopsis
      cells: induction by calcium and heat shock.
AB  - Expression of the calmodulin-related TCH genes of Arabidopsis is strongly and
      rapidly up-regulated in plants after a variety of stimuli, including touch. As an
      approach to investigating the mechanism(s) of TCH gene regulation, a manipulable
      cell culture system in which TCH gene expression is regulated has been developed.
      In response to increased external calcium or heat shock, TCH2, -3, and -4 mRNA
      levels significantly increased. Significantly, these two stimuli are known to
      result in cytoplasmic calcium increases, therefore implicating a role for calcium
      itself in the regulation of calmodulin-related genes. Further, external calcium
      is required for maximal heat-shock induction of expression of the TCH genes but
      not of the 70-kDa heat shock protein; therefore, there may exist at least two
      distinct mechanisms of heat shock induction of gene expression. Calcium ion
      regulation of genes encoding calcium-binding proteins may ensure the efficacy of
      calcium ion as a transient second messenger and the maintenance of cellular
      homeostasis. This possible regulatory circuit would likely be relevant not only
      for plant cells but also for the great variety of animal cells that transduce
      extracellular stimuli, such as hormones and electrical impulses, into calcium
      signals.

PMID- 1373490
TI  - Neuromodulatory loop mediated by nerve growth factor and interleukin 6 in thymic
      stromal cell cultures.
AB  - Neural crest cell derivatives have been suggested to be involved in thymus
      development. We established nonlymphoid thymic stromal cell cultures capable of
      supporting T-cell differentiation. In these nonlymphoid cell cultures, we
      identified cells with phenotypic and biochemical markers specific for neuronal
      cells. Neurofilament mRNA and 68- and 160-kDa neurofilament proteins, as well as
      74-kDa synapsin I isoform, were expressed in many of the cultured cells. For
      example, neurofilament immunoreactivity was detected in 20-30% of the cells. To
      see whether thymic neuronal-like cells were involved in a neural differentiation
      pathway, we investigated the effect of nerve growth factor (NGF) and interleukin
      6 (IL-6), two known neurotrophic factors. The expression of the above-described
      neural markers was enhanced by NGF and IL-6, which we report to be produced in an
      autocrine way by thymic stromal cell cultures. Finally, we found that IL-6 gene
      expression in these cell cultures was enhanced by NGF. Evidence is thus offered
      of a neuromodulatory loop within the thymic stromal cell population supported by
      local production of NGF and IL-6 and involving neural cell elements.
      Interestingly, IL-6, which is known to be implicated in thymocyte
      differentiation, also displays a neuromodulatory activity on thymic stromal
      cells, suggesting a multivalent role for this cytokine within the thymus.

PMID- 1373492
TI  - Reaction kinetic model of a proposed plasma membrane two-cycle H(+)-transport
      system of Chara corallina.
AB  - Biophysical and numerical analysis methods were used to characterize and model
      the transport protein that gives rise to the acid and alkaline regions of Chara.
      A measuring system that permits the detection of area-specific current-voltage
      curves was used. These current-voltage curves, obtained from the inward current
      regions of Chara, underwent a parallel shift when the alkaline region was
      inverted by means of an acid pH treatment. In this situation the reversal
      potential of this area shifted from -120 mV to -340 mV. Together with data
      obtained from experiments using a divided chamber system, these results suggest
      that a common transport protein generates inward and outward current regions of
      Chara. On the basis of these experimental findings, a reaction kinetic model is
      proposed that assigns two operational modes to the proposed transport protein.
      Switching between these modes generates either acid or alkaline behavior. Since
      the observed pH dependence of the postulated transporter is rather complex, a
      reaction kinetic saturation mechanism had to be incorporated into the model. This
      final 10-state reaction kinetic model provides an appropriate set of mathematical
      relations to fit the measured current-voltage curves by computer.

PMID- 1373494
TI  - Genes regulating the plant cell cycle: isolation of a mitotic-like cyclin from
      Arabidopsis thaliana.
AB  - A key element of cell cycle control in eukaryotes is the M-phase kinase, composed
      of p34cdc2 and cyclin. To dissect the plant cell cycle, we have previously
      isolated a cdc2 gene homolog from Arabidopsis thaliana. We have now cloned an
      Arabidopsis cDNA corresponding to cyclins. This gene (cyc1At) encodes a protein
      with a predicted molecular mass of 48.4 kDa and a domain homologous to the cyclin
      box of mitotic cyclins. However, by sequence comparison the cyc1At gene could not
      be assigned to the A- or B-type group. The mRNA accumulates preferentially in
      actively dividing cells and when these cells are blocked during the cell cycle,
      the amount of transcripts decreases dramatically. cyc1At mRNA is found mainly in
      G2-phase nuclei, suggesting that its expression is periodic in the cell cycle.
      Microinjection of synthetic cyc1At mRNA induced meiotic maturation in Xenopus
      oocytes. Cyc1At is encoded by a single gene, but the amplification by the
      polymerase chain reaction of other fragments homologous to cyclins indicates the
      presence of a family of cyclins in Arabidopsis.

PMID- 1373493
TI  - The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated
      with immunodeficiency.
AB  - Homozygosity for the severe combined immunodeficiency (scid) mutation results in
      a block in T- and B-lymphocyte development. An unusually high incidence of
      spontaneous thymic lymphoma development was observed after transfer of this
      mutation from the C.B-17 congenic strain background onto the diabetes-susceptible
      nonobese diabetic (NOD) background. Thymomagenesis in the NOD-scid/scid mouse was
      associated with expression of an NOD mouse-unique endogenous ecotropic murine
      leukemia provirus locus (Emv-30, mapped to proximal region of chromosome 11) not
      expressed in the standard substrain NOD/Lt thymus. All tumors exhibited
      insertions of ecotropic proviruses, whereas only a subset also exhibited proviral
      integrations of mink cell focus-forming retrovirus. Neither class of retrovirus
      was associated with consistent integration into genes previously associated with
      activation of oncogenesis. We propose that the unusual features of T-cell
      ontogeny characteristic of the NOD inbred strain synergize with the scid-imparted
      block in thymocyte development, leading to activation of the NOD-unique Emv-30 to
      initiate thymomagenesis.

PMID- 1373495
TI  - Characterization of the murine BEK fibroblast growth factor (FGF) receptor:
      activation by three members of the FGF family and requirement for heparin.
AB  - The bek gene encodes a member of the high-affinity fibroblast growth factor
      receptor family. The BEK/FGFR-2 receptor is a membrane-spanning tyrosine kinase
      with the typical features of FGF receptors. We have cloned a murine bek cDNA and
      expressed it in receptor-negative Chinese hamster ovary cells and in 32D myeloid
      cells. The BEK receptor expressed in Chinese hamster ovary cells binds acidic
      FGF, basic FGF, and Kaposi FGF equally well but does not bind keratinocyte growth
      factor or FGF-5 appreciably. Upon treatment with basic FGF or Kaposi FGF, the BEK
      receptor is phosphorylated and a mitogenic response is achieved. Heparan sulfate
      proteoglycans have been shown to play an obligate role in basic FGF binding to
      the high-affinity FLG receptor. Unlike the BEK-expressing Chinese hamster ovary
      cells, 32D cells expressing the BEK receptor require the addition of exogenous
      heparin in order to grow in the presence of basic FGF or Kaposi FGF. We show that
      the addition of heparin greatly enhances the binding of radio-labeled basic FGF
      to the receptor. Thus the BEK receptor, like FLG, also requires an interaction
      with heparan sulfate proteoglycans to facilitate binding to its ligands.

PMID- 1373496
TI  - FDC-P1 myeloid cells engineered to express fibroblast growth factor receptor 1
      proliferate and differentiate in the presence of fibroblast growth factor and
      heparin.
AB  - Full-length murine fibroblast growth factor (FGF) receptor 1 (FGFR-1L) cDNA was
      introduced into the FDC-P1 mouse myeloid progenitor cell line, which lacks FGF
      receptors and depends on interleukin 3 (IL-3) or granulocyte/macrophage colony
      stimulating factor (GM-CSF) for its proliferation and survival. The expression of
      the FGFR-1L gene in FDC-P1 cells allowed these cells to grow in the presence of
      FGF and heparin. The resulting cell line, designated FD FGFR-1L.A, exhibited a
      more mature myeloid phenotype than did the parental FD FGFR-1L cells or
      uninfected FDC-P1 cells. They formed mainly dispersed colonies in soft-agar
      cultures when grown in the presence of FGF and heparin, suggestive of myeloid
      differentiation. The cells can be switched between growth on FGF/heparin and IL
      3. Northern blot analysis and cytochemical staining demonstrated that FD FGFR
      1L.A cells expressed myeloperoxidase mRNA and protein, biochemical markers
      specifically expressed during differentiation from the promyelocytic to the
      granulocytic stages, whereas the parental FD FGFR-1L cells and FDC-P1 cells
      failed to express this marker. These results indicate that the expression of FGFR
      1L by FDC-P1 cells transmitted signals for growth in the presence of FGF and
      heparin and generated an additional signal for early myeloid differentiation but
      failed to commit FD FGFR-1L.A cells to terminal differentiation. This in vitro
      culture system can be used for molecular analysis of the regulation of cellular
      growth and differentiation mediated by the FGFs and their receptors.

PMID- 1373497
TI  - Galanin-mediated control of pain: enhanced role after nerve injury.
AB  - The endogenous inhibitory role of the neuropeptide galanin in pain transmission
      and spinal cord excitability was demonstrated by the use of a high-affinity
      galanin receptor antagonist, M-35 [galanin-(1-13)-bradykinin-(2-9)-amide]. M-35,
      which displaced 125I-labeled galanin from membranes of rat dorsal spinal cord
      with an IC50 of 0.3 nM, dose-dependently antagonized the effect of intrathecal
      galanin on the flexor reflex. M-35 potentiated the facilitation of the flexor
      reflex by conditioning stimulation of cutaneous unmyelinated afferents in rats
      with intact nerves and the potentiating effect of M-35 on the conditioning
      stimulation-induced reflex facilitation of the cutaneous unmyelinated afferents
      was strongly enhanced after axotomy. These results demonstrate that endogenous
      galanin plays a tonic inhibitory role in the mediation of spinal cord
      excitability, and it is particularly noteworthy that this function of galanin is
      remarkably enhanced after peripheral nerve section.

PMID- 1373498
TI  - Altering the antigenicity of proteins.
AB  - To better understand the binding interaction between antigen and antibody we need
      to distinguish protein residues critical to the binding energy and mechanism from
      residues merely localized in the interface. By analyzing the binding of
      monoclonal antibodies to recombinant wild-type and mutant myohemerythrin (MHr)
      proteins, we were able to test the role of individual critical residues at the
      highly antigenic site MHr-(79-84), within the context of the folded protein. The
      results directly show the existence of antigenically critical residues, whose
      mutations significantly reduce antibody binding to the folded protein, thus
      verifying peptide-based assignments of these critical residues and demonstrating
      the ability of buried side chains to influence antigenicity. Taken together,
      these results (i) distinguish the antigenic surface from the solvent-exposed
      protein surface before binding, (ii) support a two-stage interaction mechanism
      allowing inducible changes in protein antigens by antibody binding, and (iii)
      show that protein antigenicity can be significantly reduced by alteration of
      single critical residues without destroying biological activity.

PMID- 1373499
TI  - The membrane IgM-associated proteins MB-1 and Ig-beta are sufficient to promote
      surface expression of a partially functional B-cell antigen receptor in a
      nonlymphoid cell line.
AB  - The B-cell antigen receptors consist of membrane immunoglobulins (mIgs)
      noncovalently associated with two accessory proteins, MB-1 and Ig-beta. We used
      transfection into a nonlymphoid cell line to test whether MB-1 and Ig-beta were
      sufficient to promote cell surface expression of mIgM capable of signal
      transduction. Expression of MB-1 and Ig-beta, but not MB-1 alone, allowed high
      level surface expression of mIgM in the AtT20 endocrine cell line, which
      presumably lacks other B-cell-specific components. The reconstituted antigen
      receptor was capable of mediating some of the signaling reactions characteristic
      of mIgM in B lymphocytes. Crosslinking mIgM on transfected AtT20 cells stimulated
      tyrosine phosphorylation of MB-1 and Ig-beta and also increased the amount of
      phosphatidylinositol 3-kinase activity that could be precipitated with anti
      phosphotyrosine antibodies. When total cell lysates were analyzed by anti
      phosphotyrosine immunoblotting, however, no induced phosphorylation of more
      abundant proteins was detected. Moreover, crosslinking of the receptor in AtT20
      cells did not stimulate inositol phospholipid breakdown. Thus, the transfected B
      cell antigen receptor could initiate some signal transduction events but AtT20
      cells may lack components required for other signaling events associated with
      mIgM.

PMID- 1373500
TI  - Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers.
AB  - Overexpression of the p53 protein, resulting from gene mutations that increase
      protein stability, has been detected in greater than 25% of primary human breast
      cancers. In addition, approximately 10% of breast cancer patients have
      circulating antibodies to the p53 protein. In this study, the anti-p53 humoral
      response is correlated with the presence and type of mutant p53 protein expressed
      in the tumor. In a series of 60 breast cancer patients, 0 of 30 tumors with
      normal, low-level p53 expression induced anti-p53 antibodies, whereas 7 (23%) of
      30 tumors with p53 overexpression elicited a specific anti-p53 antibody response.
      These 7 patients had anti-p53 antibodies that recognized wild-type p53 and a
      variety of mutant p53 proteins. A comparison of p53 mutations revealed that
      antibody-negative tumors had mutations exclusively in exons 7 and 8, whereas
      antibody-positive tumors had mutations primarily in exons 5 and 6. Moreover, all
      antibody-eliciting tumors contained complexes between p53 and a 70-kDa heat shock
      protein, whereas none of the antibody-negative tumors contained this complex.
      This study implicates a 70-kDa heat shock protein in the antigenic presentation
      of p53.

PMID- 1373501
TI  - Selectively amplified expression of an isoform of the vacuolar H(+)-ATPase 56
      kilodalton subunit in renal intercalated cells.
AB  - The intercalated cells of the kidney collecting duct are specialized for
      physiologically regulated proton transport. In these cells, a vacuolar H(+)
      ATPase is expressed at enormous levels in a polarized distribution on the plasma
      membrane, enabling it to serve in transepithelial H+ transport. In contrast, in
      most eukaryotic cells, vacuolar H(+)-ATPases reside principally in intracellular
      compartments to effect vacuolar acidification. To investigate the basis for the
      selective amplification of the proton pump in intercalated cells, we isolated and
      sequenced cDNA clones for two isoforms of the approximately 56-kDa subunit of the
      H(+)-ATPase and examined their expression in various tissues. The predicted amino
      acid sequence of the isoforms was highly conserved in the internal region but
      diverged in the amino and carboxyl termini. mRNA hybridization to a cDNA probe
      for one isoform (the "kidney" isoform) was detected only in kidney cortex and
      medulla, whereas mRNA hybridization to the other isoform of the approximately 56
      kDa subunit and to the H(+)-ATPase 31-kDa subunit was found in the kidney and
      other tissues. Immunocytochemistry of rat kidney with an antibody specific to the
      kidney isoform revealed intense staining only in the intercalated cells. Staining
      was absent from proximal tubule and thick ascending limb, where H(+)-ATPase was
      detected with a monoclonal antibody to the 31-kDa subunit of the H(+)-ATPase.
      This example of specific amplification of an isoform of one subunit of the
      vacuolar H(+)-ATPase being limited to a specific cell type suggests that the
      selective expression of the kidney isoform of the approximately 56-kDa subunit
      may confer the capacity for amplification and other specialized functions of the
      vacuolar H(+)-ATPase in the renal intercalated cell.

PMID- 1373502
TI  - Role and regulation of interleukin (IL)-2 receptor alpha and beta chains in IL-2
      driven B-cell growth.
AB  - Substantial proportions of resting B cells constitutively express low levels of
      IL-2 receptor (IL-2R) alpha and/or beta chains. The expression of these chains is
      differentially regulated by anti-IgM and IL-2/IL-4. The anti-IgM induces IL-2R
      alpha chain expression, whereas each of the two cytokines induces IL-2R beta
      chain expression in a dose-dependent manner. Moreover, IL-2 induces the growth of
      B cells, when the cells were pretreated with IL-2 or IL-4 for 24 h. The magnitude
      of this IL-2-driven B-cell growth depends upon the level of IL-2R beta chain
      expression. Costimulation of the B cells with IL-2 and anti-IgM shifts the dose
      response curve, and the cells proliferate at an IL-2 concentration as low as 40
      pM. These results indicate that the levels of anti-IgM-induced IL-2R alpha chain
      and IL-2-induced IL-2R beta chain determine the sensitivity of the cells to IL-2.

PMID- 1373503
TI  - Cyclic AMP induces transforming growth factor beta 2 gene expression and growth
      arrest in the human androgen-independent prostate carcinoma cell line PC-3.
AB  - The standard therapy for advanced prostate cancer is androgen ablation. Despite
      transitory responses, hormonally treated patients ultimately relapse with
      androgen-independent disease that is resistant to further hormonal manipulation
      and cytotoxic chemotherapy. To develop an additional approach to the treatment of
      advanced prostate cancer, we have been studying the signal transductions
      controlling the growth of human androgen-independent prostate carcinoma cell
      lines. We report here that elevation of intracellular cAMP markedly inhibits the
      growth of the hormone-refractory cell line PC-3. To examine the mechanism of cAMP
      action in PC-3 cells, we tested the effect of the cAMP analog dibutyryl cAMP (Bt2
      cAMP) on the regulation of the potent negative growth factor transforming growth
      factor beta (TGF-beta). Bt2-cAMP selectively induced the secretion of TGF-beta 2
      and not TGF-beta 1 by PC-3 cells. This TGF-beta 2 was shown to be bioactive by
      using the CCL-64 mink lung cell assay. TGF-beta 1 was not activated despite being
      present at 3-fold higher concentrations than TGF-beta 2. Northern analysis showed
      that Bt2-cAMP induced an increase in the five characteristic TGF-beta 2
      transcripts and had no effect on the level of TGF-beta 1 or TGF-beta 3
      transcripts. TGF-beta 2 induction was only weakly enhanced by cycloheximide and
      was completely inhibited by actinomycin D. These data show that Bt2-cAMP induces
      the expression of active TGF-beta 2 by PC-3 prostate carcinoma cells, suggesting
      a new approach to the treatment of prostate cancer and a new molecular mechanism
      of cAMP action.

PMID- 1373504
TI  - Expression cloning and characterization of the canine parietal cell gastrin
      receptor.
AB  - Gastrin is an important stimulant of acid secretion by gastric parietal cells and
      is structurally related to the peptide hormone cholecystokinin (CCK). The
      pharmacologic properties of the parietal cell gastrin receptor are very similar
      to the predominant CCK receptor in the brain, CCK-B. Neither the gastrin nor the
      CCK-B receptor have been cloned thus far, making it difficult to resolve whether
      these two receptors are distinct. We have isolated a clone encoding the canine
      gastrin receptor by screening a parietal cell cDNA expression library using a
      radioligand-binding strategy. Nucleotide sequence analysis revealed an open
      reading frame encoding a 453-amino acid protein with seven putative hydrophobic
      transmembrane domains and significant homology with members of the beta
      adrenergic family of G protein-coupled receptors. The expressed recombinant
      receptor shows the same binding specificity for gastrin/CCK agonists and
      antagonists as the canine parietal cell receptor. Gastrin-stimulated
      phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization in COS-7
      cells expressing the cloned receptor suggest second-messenger signaling through
      phospholipase C. Affinity labeling of the expressed receptor in COS-7 cells
      revealed a protein identical in size to the native parietal cell receptor.
      Gastrin receptor transcripts were identified by high-stringency RNA blot analysis
      in both parietal cells and cerebral cortex, suggesting that the gastrin and CCK-B
      receptors are either highly homologous or identical.

PMID- 1373505
TI  - Molecular mechanisms of the partial allosteric modulatory effects of bretazenil
      at gamma-aminobutyric acid type A receptor.
AB  - In central nervous system gamma-aminobutyric acid (GABA) inhibits neuronal
      activity by acting on GABA type A (GABAA) receptors. These heterooligomeric
      integral membrane proteins include a GABA-gated Cl- channel and various
      allosteric modulatory sites where endogenous modulators and anxiolytic drugs act
      to regulate GABA action. In vivo, various anxiolytic drugs exhibit a wide range
      of variability in their modulatory efficacy and potency of GABA action. For
      instance, bretazenil modulatory efficacy is much lower than that of diazepam.
      Such low efficacy could be due either to a preferential modulation of specific
      GABAA receptor subtypes or to a low modulatory efficacy at every GABAA receptor
      subtype. To address these questions we studied drug-induced modifications of GABA
      activated Cl- currents in native GABAA receptors of cortical neurons in primary
      cultures and in recombinant GABAA receptors transiently expressed in transformed
      human embryonic kidney cells (293) after transfection with cDNAs encoding
      different molecular forms of alpha, beta, and gamma subunits of GABAA receptors.
      In cortical neurons the efficacy of bretazenil was lower than that of diazepam,
      whereas the potency of the two drugs was similar. In cells transfected with gamma
      2 subunits and various molecular forms of alpha and beta subunits bretazenil
      efficacy was always lower than that of diazepam. However, in cells transfected
      with gamma 1 or gamma 3 subunits and various forms of alpha and beta subunits the
      efficacy of both diazepam and bretazenil was lower and always of similar
      magnitude. When bretazenil and diazepam were applied together to GABAA receptors
      including a gamma 2 subunit, the action of diazepam was curtailed in a manner
      related to the dose of bretazenil.

PMID- 1373506
TI  - Role of a vitronectin-like molecule in embryo adhesion of the brown alga Fucus.
AB  - The rhizoid cell of the two-celled embryo of the brown alga Fucus is structurally
      and functionally differentiated from the thallus cell. The rhizoid cell is highly
      polar and transports directionally components of the cell wall to its elongating
      tip, which attaches the developing embryo to the substratum. Polyclonal
      antibodies to human vitronectin (Vn) recognize a vitronectin-like glycoprotein
      (Vn-F) in extracts of zygotes and two-celled embryos of Fucus, with a molecular
      mass (approximately 62 kDa) similar to that of human Vn. The specificity of the
      immunological cross-reactivity of Vn-F to rabbit polyclonal antibodies made to
      human Vn is demonstrated by competition experiments using pure human Vn and
      monospecific antibodies generated toward Vn-F. Vn-F possesses affinities for
      glass and heparin that are identical to those of human Vn. Immunolocalization and
      subcellular fractionation results demonstrate that Vn-F is localized first in the
      cytoplasm of the zygote, which is followed by the polar transport of Vn-F to its
      exclusive localization in the cell wall of the elongating rhizoid tip. Vn does
      not localize to the rhizoid tip under culture conditions that prevent two-celled
      embryos from attaching. Furthermore, an adhesion assay demonstrates that two
      celled Fucus embryos do not adhere to the substratum in the presence of the Vn
      antibody, suggesting that the Vn-F in this brown alga not only possesses
      structural similarity to mammalian Vn but may also have a similar functional role
      in adhesion. The presence of Vn-F in brown algae suggests a high degree of
      evolutionary conservation of its structural and functional characteristics.

PMID- 1373507
TI  - Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of
      the high-affinity or low-affinity Fc receptor for IgG in U937 cells.
AB  - The human monocytic cell line U937 possesses two classes of the IgG Fc receptor
      (Fc gamma R), a high-affinity 72-kDa Fc gamma R (Fc gamma RI) and a low-affinity
      40-kDa Fc gamma R (Fc gamma RII). Cross-linking of either class of Fc gamma R in
      U937 cells elicits an increase in the concentration of free intracellular Ca2+. A
      rapid rise in the concentration of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3)
      and of several other inositol phosphates derived from Ins-1,4,5-P3 was observed
      after cross-linking of Fc gamma Rs in U937 cells. This result suggests that Ins
      1,4,5-P3, generated by the action of phospholipase C (PLC), acts as a second
      messenger by which Fc gamma Rs mobilize intracellular Ca2+ in U937 cells. The
      mechanism by which the cross-linking of Fc gamma Rs triggers activation of PLC
      was studied. Cross-linking of Fc gamma RI or Fc gamma RII resulted in a rapid and
      transient phosphorylation of PLC-gamma 1 on tyrosine residues. It has previously
      been shown that phosphorylation of PLC-gamma 1 on tyrosine residues activates its
      enzymatic activity in cells. Prior incubation of U937 cells with a protein
      tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation
      of PLC-gamma 1 and the hydrolysis of phosphatidylinositol 4,5-bisphosphate
      induced by the cross-linking of Fc gamma Rs. Thus, Fc gamma RI and Fc gamma RII
      appear to be functionally coupled to a nonreceptor tyrosine kinase that
      phosphorylates PLC-gamma 1 after receptor cross-linking, thereby causing
      activation of PLC-gamma 1.

PMID- 1373509
TI  - [Late pulmonary changes following bleomycin administration in computed
      tomography. Nodular fibrosis mimicking a seminoma metastasis].
AB  - This is a case report of a patient with multiple metastases to the lung due to a
      seminoma, treated with a chemotherapeutic regimen containing bleomycin. The
      typical subpleural fibrosis of the lung related to bleomycin damage disappeared 6
      months after the start of chemotherapy. 4 weeks later, a solitary nodule at a
      prior unchanged site of the lung appeared, mimicking recurrent metastasis.
      Explorative thoracotomy revealed a nodular fibrosis of the lung, representing a
      late reaction of the lung to chemotherapy damage.

PMID- 1373508
TI  - Conditioned increase of natural killer cell activity (NKCA) in humans.
AB  - Cumulating evidence suggests that immune parameters can be modified by behavioral
      conditioning processes in animals. The present results suggest that this also
      holds true for a human immune parameter. Healthy subjects were exposed to a
      conditioning procedure in which a neutral sherbet sweet (conditioned stimulus)
      was repeatedly paired with a subcutaneous injection of 0.2 mg epinephrine
      (unconditioned stimulus). After epinephrine administration an increase of natural
      killer (NK) cell activity could be observed (unconditioned response). On the
      conditioning test day the conditioned group showed increased NK cell activity
      after reexposure of the sherbet sweet combined with saline injection. No increase
      was found in control groups that previously received the sherbet sweet in
      combination with saline (saline control) or with epinephrine in an unpaired
      manner (unpaired control). This study supports previous findings of conditioned
      modulation of immune responses and represents a model to investigate conditioning
      processes of a human immune function.

PMID- 1373510
TI  - [Renal tumor embolization].
AB  - We present an update on the technical aspects and clinical efficacy of the
      concept of capillary embolization for the treatment of renal cell carcinoma. In
      preoperative indications, it is shown that only this type of occlusion can safely
      achieve a reliable breakdown of the peritumor vasculature to meet the surgical
      requirements for excision of huge tumors associated with abundant retroperitoneal
      tributaries. In particular, in tumors infiltrating the renal vein and the vena
      cava, capillary embolization proved to be extremely helpful. In palliative
      embolization the concept achieved local and clinical efficacy comparable to
      nephrectomy when applied in patients free of metastatic disease. In palliative
      embolization of patients with metastatic disease, no change in the natural
      history was found. A new but still experimental concept is the combination of
      chemoperfusion and chemoembolization for tumor nodules in a solitary kidney and
      for reoccurring retroperitoneal tumors. The application of a coaxial system that
      features perfect maneuverability enables tumor treatment on the level of
      subsegmental vessels. The first short-term results seem to be promising. If
      definite proof of the validity of such a concept is to be obtained, however,
      further long-term research needs to be conducted on larger numbers of patients.

PMID- 1373511
TI  - [Pneumopathy secondary to the improper use of a dust-removing spray].
AB  - We report the case of a 24 year-old woman who presented constitutional symptoms
      with dyspnoea on exertion accompanied by an interstitial pneumonitis in both
      lower lobes. The history revealed an excessive use of household dust-away
      cleansing spray. The diagnosis was established by bronchoalveolar lavage
      associated with appropriate steining. The early diagnosis is critical because of
      the progression to fibrosis and the risk of cancerisation.

PMID- 1373512
TI  - Function of lipopolysaccharide (LPS)-binding protein (LBP) and CD14, the receptor
      for LPS/LBP complexes: a short review.
AB  - With the recent discovery and cloning of the lipopolysaccharide-binding protein
      (LBP), the "adapter-molecule" for LPS-binding to the cell surface receptor CD14
      was found. The ligand-receptor pair LPS/LBP-CD14 seems to be one important
      element in LPS-mediated activation of monocytic cells and possibly granulocytes
      and B cells. Here, some of the known functions of the proteins involved, LBP and
      CD14, are reviewed in the context of other endotoxin recognition studies, and the
      outlook for ongoing and future investigations is described.

PMID- 1373513
TI  - Endotoxin-neutralizing capacity of soluble CD14.
AB  - Luminol-enhanced chemiluminescence was used to determine the effect of soluble
      CD14 (sCD14) on the endotoxin-inducible generation of reactive oxygen species in
      human monocytes. It was necessary to mediate lipopolysaccharide (LPS) monocyte
      activating capability by serum factors (LPS-binding proteins). sCD14 reduced LPS
      inducible monocyte activation in a dose-dependent manner, even in the case of
      CD14- monocytes, obtained from a patient with paroxysmal nocturnal
      haemoglobinuria. These monocytes could be activated by opsonized LPS via other
      receptors. Using anti-mouse Ig-coated microbeads, it was demonstrated in FACS
      analysis that sCD14 mediates the binding of a mouse monoclonal anti-CD14 antibody
      (RoMo 1) to a complex of LPS/FITC (fluoroisothiocyanate) and a LPS-binding
      protein. The release of sCD14 from cultured monocytes was measured using LPS, TNF
      alpha (tumour necrosis factor), IL1, 4 and 6 (interleukin-1, -4 and -6) and IFN
      gamma (interferon-gamma) as stimulators. Addition of LPS and TNF alpha led to a
      dose-dependent increase in sCD14-levels in the culture supernatant, whereas IL1,
      IL6 and IFN gamma had no significant effect. IL4 dose-dependently depressed
      spontaneous sCD14 release. It is possible that elevated sCD14-serum levels in
      polytraumatized patients indicate a natural protective mechanism against
      excessive monocyte mediator production. Therefore, sCD14 may be a new therapeutic
      concept in endotoxic shock prevention.

PMID- 1373514
TI  - B-cell epitopes of the Nef protein.

PMID- 1373515
TI  - Therapeutic alternatives for hormone-refractory prostatic cancer.
AB  - The currently available prognostic factors allow the identification of patients
      who are destined to do poorly with primary hormone therapy. Standardization of
      these factors is required so that they become incorporated into routine practice.
      For patients who relapse in osseous sites radiolabeled diphosphonates are one
      therapeutic alternative that can provide palliation. Future use will be directed
      to optimize treatment schedules, and use earlier in the course of the disease so
      that more durable palliation of bony metastases can be achieved. Evolving data on
      the use of PSA show that elevations antedate clinical relapse for most patients.
      In these cases, sequential changes can be used to assess therapeutic effects,
      which in turn can allow novel therapies to be screened more rapidly in the
      clinic. Criteria for the degree of change that is indicative of response must be
      standardized. Preliminary data suggest a 50% decline be the minimum that is used.
      The results with agents such as suramin, which interrupts autocrine and paracrine
      growth factor loops, are a therapeutic strategy that need further study. Future
      efforts will focus on defining which patients are best suited for specific
      therapeutic approaches.

PMID- 1373516
TI  - [The outcome of resuscitated infants. Experience at an African university
      maternity unit].
AB  - The authors report a study involving 90 infants born at term or close to term and
      who required resuscitation at birth for per-natal fetal distress. These were 16.6
      per cent early deaths (between 0 and 7 days), 11.1 per cent of infants lost to
      follow-up, 11.1 per cent of infants dying from various causes unrelated to their
      history of neonatal resuscitation and 16.6 per cent of cases considered
      unevaluable because of incomplete records. In a second section, they compare 40
      resuscitated children (44.4 per cent of the initial sample) with 40 controls of
      the same age from a clinical, psychomotor and scholastic standpoint. They noted
      no significant difference regarding clinical and psychomotor status. Results
      concerning scholastic achievement, with the notable role played by socio-economic
      circumstances, must be interpreted with caution. At any event, results here are
      identical in general to those reported in other publications devoted to the same
      subject.

PMID- 1373517
TI  - Biological roles of nitric oxide.

PMID- 1373518
TI  - CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes.
AB  - Lymphocytes must proliferate and differentiate in response to low concentrations
      of a vast array of antigens. The requirements of broad specificity and
      sensitivity conflict because the former is met by low-affinity antigen receptors,
      which precludes achieving the latter with high-affinity receptors. Coligation of
      the membrane protein CD19 with the antigen receptor of B lymphocytes decreased
      the threshold for antigen receptor-dependent stimulation by two orders of
      magnitude. B lymphocytes proliferated when approximately 100 antigen receptors
      per cell, 0.03 percent of the total, were coligated with CD19. The B cell
      resolves its dilemma by having an accessory protein that enables activation when
      few antigen receptors are occupied.

PMID- 1373519
TI  - The disulfide folding pathway of BPTI.

PMID- 1373520
TI  - Molecular cloning of the interleukin-1 beta converting enzyme.
AB  - Interleukin-1 beta (IL-1 beta) mediates a wide range of immune and inflammatory
      responses. The active cytokine is generated by proteolytic cleavage of an
      inactive precursor. A complementary DNA encoding a protease that carries out this
      cleavage has been cloned. Recombinant expression in COS-7 cells enabled the cells
      to process precursor IL-1 beta to the mature form. Sequence analysis indicated
      that the enzyme itself may undergo proteolytic processing. The gene encoding the
      protease was mapped to chromosomal band 11q23, a site frequently involved in
      rearrangement in human cancers.

PMID- 1373521
TI  - Context dependence of hydrogen bond free energy revealed by substitutions in an
      RNA hairpin.
AB  - Prediction and modeling of RNA structure requires knowledge of the free energy
      contributions of various interactions. Many unusual hydrogen bonds were recently
      proposed in the structure of a GCAA hairpin determined from nuclear magnetic
      resonance. The contributions of these hydrogen bonds to the folding stability of
      the hairpin formed by rGGCGCAAGCC have now been investigated through the use of
      functional group substitutions. These and previous results suggest a strong
      context dependence for the free energy of hydrogen bond formation. The results
      also suggest that the phylogenetic preference for GNRA (where N = A, C, G, or U
      and R = A or G) tetraloops may have a functional rather than thermodynamic basis.

PMID- 1373522
TI  - Cloning and characterization of inducible nitric oxide synthase from mouse
      macrophages.
AB  - Nitric oxide (NO) conveys a variety of messages between cells, including signals
      for vasorelaxation, neurotransmission, and cytotoxicity. In some endothelial
      cells and neurons, a constitutive NO synthase is activated transiently by
      agonists that elevate intracellular calcium concentrations and promote the
      binding of calmodulin. In contrast, in macrophages, NO synthase activity appears
      slowly after exposure of the cells to cytokines and bacterial products, is
      sustained, and functions independently of calcium and calmodulin. A monospecific
      antibody was used to clone complementary DNA that encoded two isoforms of NO
      synthase from immunologically activated mouse macrophages. Liquid chromatography
      mass spectrometry was used to confirm most of the amino acid sequence. Macrophage
      NO synthase differs extensively from cerebellar NO synthase. The macrophage
      enzyme is immunologically induced at the transcriptional level and closely
      resembles the enzyme in cytokine-treated tumor cells and inflammatory
      neutrophils.

PMID- 1373523
TI  - Diacylglycerol-stimulated formation of actin nucleation sites at plasma
      membranes.
AB  - Diacylglycerols, which are generated during phospholipase-catalyzed hydrolysis of
      phospholipids, stimulated actin polymerization in the presence of highly purified
      plasma membranes from the cellular slime mold Dictyostelium discoideum. The
      increased rate of actin polymerization apparently resulted from de novo formation
      of actin nucleation sites rather than uncapping of existing filament ends,
      because the membranes lacked detectable endogenous actin. The increased actin
      nucleation was mediated by a peripheral membrane component other than protein
      kinase C, the classical target of diacylglycerol action. These results indicate
      that diacylglycerols increase actin nucleation at plasma membranes and suggest a
      mechanism whereby signal transduction pathways may control cytoskeletal assembly.

PMID- 1373524
TI  - Appearance of water channels in Xenopus oocytes expressing red cell CHIP28
      protein.
AB  - Water rapidly crosses the plasma membrane of red blood cells (RBCs) and renal
      tubules through specialized channels. Although selective for water, the molecular
      structure of these channels is unknown. The CHIP28 protein is an abundant
      integral membrane protein in mammalian RBCs and renal proximal tubules and
      belongs to a family of membrane proteins with unknown functions. Oocytes from
      Xenopus laevis microinjected with in vitro-transcribed CHIP28 RNA exhibited
      increased osmotic water permeability; this was reversibly inhibited by mercuric
      chloride, a known inhibitor of water channels. Therefore it is likely that CHIP28
      is a functional unit of membrane water channels.

PMID- 1373525
TI  - Morphologic and quantitative changes in neurotransmitters in the lumbar spinal
      cord after acute or chronic mechanical compression of the cauda equina.
AB  - Changes in the neurotransmitters associated with pain transmission and regulation
      in the lumbar spinal cord were studied after acute or chronic mechanical
      compression of the cauda equina in rats. Using glyoxylic acid histofluorescence
      and immunohistochemical methods, it was morphologically apparent that substance P
      containing nerve ending were decreased after chronic compression of the cauda
      equina. Somatostatin nerve terminals were reduced, and aminergic fibers and
      serotonin were enhanced after both acute and chronic mechanical compressions. In
      addition, quantitative analysis revealed that the levels of norepinephrine and
      serotonin remained elevated after mechanical compression of the cauda equina. It
      is suggested that pain in the lower back and extremities after mechanical
      compression of the cauda equina is controlled by these complicated changes of
      neurotransmitters in the lumbar spinal cord.

PMID- 1373526
TI  - The risk of major audiovisual problems during ophthalmic presentations.

PMID- 1373527
TI  - Metallothionein of prostatic tissues and fluids in rats and humans.
AB  - We analyzed metallothionein (MT) in rat prostates by gel filtration and
      radioimmunoassay. The concentration of MT in the prostate, kidney and liver of
      cadmium-induced rats was measured. The concentration of MT was also measured in
      normal prostate, benign prostatic hyperplasia, prostate cancer and the prostatic
      fluids from various prostatic diseases in humans. MT was detected in rat
      prostates by gel filtration and radioimmunoassay. The concentration of MT
      (micrograms/g wet tissue) was 0.3 +/- 0.1 (S.D.) in the ventral lobe, 30.4 +/-
      24.0 in the lateral lobe, 5.2 +/- 0.9 in the dorsal lobe, 25.0 +/- 6.4 in the
      kidney and 2.0 +/- 1.5 in the liver of the rat control group. Change in MT
      content in CdCl2-induced organs increased quantitatively with the dose
      administered. The concentration of MT (micrograms/g wet tissue) in human prostate
      was 99.3 +/- 121.8 in the peripheral zone (PZ), 12.0 +/- 8.5 in the preprostatic
      region (PR), 7.3 +/- 3.1 in the central zone (CZ), 17.5 +/- 15.0 in benign
      hyperplastic nodules (A) and 4.2 +/- 0.5 in cancer tissue (CA). MT concentration
      in PZ was very high and that of CA, low (p less than 0.05). MT concentration in
      prostatic fluids (ng/mg protein) was 11.5 +/- 5.7 in normal patients, 3.8 +/- 2.3
      in acute prostatitis, 6.5 +/- 3.7 in chronic prostatitis with pyuria, 39.6 +/-
      3.9 in chronic prostatitis without pyuria and 16.9 +/- 3.0 in benign prostatic
      hyperplasia. We concluded that MT in the prostate is induced by heavy metals and
      secreted into prostatic fluid. Possibly, it is a marker of secretory function in
      the prostate.

PMID- 1373528
TI  - Characterization of three T-lymphoid cell lines with distinct sensitivities to
      deoxyadenosine plus deoxycoformycin.
AB  - Three established human T-cell lines, HPB-MLT, HPB-ALL and PEER, were
      characterized and tested for their sensitivity to deoxyadenosine (dAdo) plus
      deoxycoformycin (dCoF). Phenotypic characterizations showed that all three cell
      lines had receptors for peanut agglutinin (PNA) and soybean agglutinin (SBA)
      while HPB-MLT and HPB-ALL, but not PEER, expressed the cortical thymocyte
      specific marker, CD1. The majority of HPB-MLT cells (88%) expressed only CD4 but
      not CD8 antigen while most HPB-ALL cells (81%) co-expressed CD8 and CD4 antigens.
      PEER cells were negative for both CD8 and CD4. These three T cell lines showed
      differential sensitivity to dAdo plus dCoF in consequent tests. dAdo or dAdo plus
      dCoF (1 microM) had no effect on the growth, or DNA and RNA synthesis of HPB-MLT
      cells while the combination of dAdo and dCoF partially inhibited cellular growth
      and DNA and RNA synthesis of HPB-ALL cells. Further, the growth and DNA and RNA
      synthesis of PEER cells were strongly inhibited by the combination of dAdo and
      dCoF. This high sensitivity to dAdo plus dCoF reflected an immature phenotype of
      PEER cells despite its expression of CD3. Flow cytometric analysis of PEER cells
      demonstrated disappearance of the G2/M phase cells from the cell cycle after
      treatment with dAdo plus dCoF. Measurements of adenosine deaminase (ADA) and
      purine nucleoside phosphorylase (PNP) activities in all three cell lines,
      however, did not establish correlations between purine metabolizing enzyme
      activities and the differential sensitivities to dAdo plus dCoF. In sum, we
      report here three T-cell lines of different phenotypes that displayed
      significantly different sensitivities to dAdo plus dCoF which may facilitate
      investigations on the mechanisms of ADA deficiency.

PMID- 1373529
TI  - Prevalence and level of antibodies to the circumsporozoite proteins of human
      malaria parasites, including a variant of Plasmodium vivax, in the population of
      two epidemiologically distinct areas in the state of Acre, Brazil.
AB  - A seroepidemiological study of the prevalence of antibodies against the repeating
      epitopes of circumsporozoite (CS) proteins of human malaria parasites was
      conducted in 2 different areas in the state of Acre, Brazil in 1987 and 1990. In
      1987 antibodies against the CS protein of the VK 247 variant Plasmodium vivax as
      well as antibodies against the CS proteins of P. falciparum and the classic P.
      vivax were found at relatively high rates in the 2 areas, but significant
      microepidemiological differences were observed. In 1990, when large scale
      migration in Amazonia had ceased and control measures were applied in the study
      areas, the malaria endemicity decreased, as determined by the declining
      prevalence of anti-sporozoite antibodies against all Plasmodium species, and the
      small number of individuals with positive blood smears. Antibodies against
      sporozoites of the variant P. vivax did not cross-react with the CS proteins of
      the classic P. vivax, nor with antibodies against sporozoites of P. falciparum
      and P. malariae. Sera containing antibodies against the CS protein of P. malariae
      were found at a very low frequency, and only in 1987. The anti-CS protein
      antibody response to all Plasmodium species was age-related.

PMID- 1373530
TI  - Apolipoprotein B mRNA editing: a new tier for the control of gene expression.
AB  - Two forms of apolipoprotein (apo) B are found in mammals. The shorter form is
      translated from an edited mRNA in which a specific cytidine base is deaminated to
      a uridine, creating a new stop codon. Apo B mRNA editing is mediated by a site
      specific cytidine deaminase that recognizes a downstream target sequence in the
      RNA. The enzyme has no energy or cofactor requirements and no RNA component, and
      thus bears no obvious relationship to RNA processing events such as splicing or
      polyadenylation. While apo B mRNA editing activity may have arrived late in
      evolution to target dietary lipid to the liver in mammals, the discovery of the
      editing activity in tissues and cells that do not express apo B suggests a more
      widespread role in the generation of RNA and protein diversity.

PMID- 1373531
TI  - The effect of bile duct ligation and bile diversion on FK506 pharmacokinetics in
      dogs.
AB  - Mongrel or beagle dogs were submitted to bile duct ligation, or to extraenteric
      biliary diversion by means of choledochoureterostomy. The kinetics of
      intravenously administered FK506 was not changed from control status two weeks
      after bile duct ligation, but the bioavailability of orally administered FK506
      was nearly quadrupled. Following oral administration, the absorption of FK506 was
      highly variable. The results indicate that in dogs FK506 is absorbed from the
      intestine just as efficiently in the absence of enteric bile and in presence of
      exogenous bile salt supplement when compared with its absorption in presence of
      normal bile drainage. These findings with FK506 are different from those with
      cyclosporine after biliary obstruction or diversion and will have important
      practical as well as experimental ramifications.

PMID- 1373532
TI  - The importance of a colloid in canine pancreas preservation.
AB  - The role of hydroxyethyl starch (HES), the colloid component of the UW solution,
      was tested in canine pancreas preservation. Segmental pancreatic autografts were
      preserved for 48 hr cold storage with UW solution with HES (group 1) or UW
      solution without HES (group 2). After preservation, the pancreas was
      transplanted, and survival, serum glucose, serum amylase, intravenous glucose
      tolerance tests, tissue water content, and histology were compared between
      groups. In group 1 (with HES), 9/10 dogs were long-term survivors with one dog
      dying due to causes unrelated to preservation failure. In group 2 (without HES),
      3/6 dogs died due to graft loss within one week posttransplant (P = 0.01). No
      graft failure occurred in group 1 (0/9) versus graft loss in 4/6 dogs in group 2
      (P = 0.04). All animals in group 1 (with HES) showed normal serum glucose and
      amylase concentrations postoperatively, normal tissue water values after
      preservation, k values comparable to those observed after segmental
      autotransplantation without preservation, and relatively good histology. In group
      2 (without HES), in 4/6 dogs graft failure occurred that led to the death (3
      dogs) of the animals or to a diabetic state (1 dog). After 48-hr cold storage
      without HES, a significant increase in tissue water content, glucose and amylase
      levels was seen. After transplantation, hyperglycemia, hyperamylasemia, and
      clinical diabetes were observed in 4/6 dogs. Autopsy and histological evaluation
      showed evidence of thrombosis and ischemic insult. Two of 6 dogs in group 2
      remained normoglycemic during follow-up with borderline k values. The results
      suggested that for consistently successful 48-hr preservation of the pancreas,
      HES is an important component of the UW solution. Although a colloid may not be
      essential for short-term preservation of kidney and liver, it appears to be an
      important factor in successful pancreas preservation.

PMID- 1373533
TI  - A new dextran 40-based solution for liver preservation.
AB  - UW solution is at present the most efficient solution for preservation of livers
      for transplantation. We have developed an alternative solution based on dextran
      instead of hydroxyethyl starch and without raffinose, allopurinol, magnesium
      sulfate, insulin, penicillin, or dexamethasone, which all are used in UW
      solution. In addition, 62.5 mM potassium in UW solution is replaced with sodium.
      We tested this new solution for liver preservation using the isolated perfused
      rabbit liver. We found that livers preserved in the UW solution for 24 or 48 hr
      lost 11.6 +/- 2.6% and 16.8 +/- 2.0% of the prepreservation weight, respectively,
      as a sign of organ shrinkage (P less than 0.001). In contrast, no change in liver
      weight was observed after preservation in the new dextran-based solution.
      Similarly, no change in total tissue water of the rat liver slices was seen after
      preservation in the new solution. Furthermore, livers preserved for 24 hr in the
      UW solution or the new solution produced the same amount of bile as unpreserved
      livers. However, after preservation in the UW solution for 48 hr, bile production
      was reduced by 65% (P less than 0.05). In contrast, livers preserved for 48 hr in
      the new solution showed no reduction in bile production. We conclude that our new
      solution significantly improves long-term liver preservation, and with this
      modified solution, 48-hr preservation may be safe.

PMID- 1373534
TI  - The clinical outcome of hepatitis C virus antibody-positive renal allograft
      recipients.
AB  - In order to investigate the prevalence of antibody to hepatitis C virus (anti
      HCV) in renal transplant patients, the evolution of anti-HCV status, and clinical
      outcome in anti-HCV-positive renal allograft recipients, we tested the sera from
      120 renal transplant patients for anti-HCV. Thirty-eight patients were hepatitis
      B surface antigen (HBsAg)-positive. Two patients were anti-delta-positive. A
      total of 79 patients (65.8%) had at least one serum positive for anti-HCV. Anti
      HCV positivity decreased after transplantation for more than 5 years (65.5% at
      transplantation versus 37.9%, 78.3 +/- 13.4 months later). Among those with
      positive anti-HCV, the HBsAg-positive group had significantly higher incidence of
      chronic hepatitis (50% vs. 25.5%, P = 0.026) and liver cirrhosis (21.4% vs. 0%, P
      = 0.001) than HBsAg-negative group. Among the 82 HBsAg-negative patients, the
      prevalence of anti-HCV was significantly higher in those with chronic hepatitis
      than in those without (86.7% vs. 56.7%, P = 0.027). We conclude from this study:
      (1) anti-HCV positivity is quite prevalent in renal transplant patients; (2)
      coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may lead to
      aggressive liver disease and cirrhosis; HCV infection alone has a more benign
      clinical outcome; and (3) HCV infection is an important cause of posttransplant
      chronic hepatitis in HBsAg-negative patients.

PMID- 1373536
TI  - Morphological and functional changes of islets of Langerhans in FK506-treated
      rats.
AB  - FK506, a new immunosuppressant, caused glucose intolerance in rats given daily
      oral doses of 1, 5, or 10 mg/kg/day for 14 days, but did not induce hyperglycemia
      under normal feeding. Besides the glucose intolerance, insulin secretion was
      impaired and insulin levels in the pancreas were lowered. Histopathologically,
      there was vacuolation of the Langerhans islets in the animals given 10 mg/kg.
      After withdrawal of the drug, these changes in pancreatic function and morphology
      returned to normal within 2 weeks. The findings indicate that FK506 caused dose
      dependent but reversible islet toxicity in rats.

PMID- 1373535
TI  - Cytomegalovirus infection of the upper gastrointestinal tract following liver
      transplantation--incidence, location, and severity in cyclosporine- and FK506
      treated patients.
AB  - One hundred and forty randomly selected liver transplant recipients were studied
      before and after primary orthotopic liver transplantation for the presence or
      absence of CMV enteritis. Following OLTx, 65 patients were treated with
      cyclosporine A and 75 were treated with FK506. The two groups were similar with
      regard to the incidence, location, and outcome of their upper gastrointestinal
      CMV infection. Prior to OLTx, only one patient had evidence of enteric CMV
      infection. The incidence of CMV enteritis post-OLTx was 27.7% in the CsA-treated
      group and 20% in the FK-treated group. During the first posttransplant month, no
      patient in the FK-treated group developed CMV enteritis, compared with 11.5% of
      the patients who were treated with CsA (P less than 0.05). Gastric CMV was found
      in over 80% of those positive for any organ in either group. In addition to CMV
      infection of the upper gastrointestinal tract, clinically evident CMV disease
      involved more nonenteric organs in the CsA-treated group than in the FK-treated
      group. In the CsA-treated group, CMV-negative patients had a statistically higher
      1-year survival rate (100%) than CMV-positive patients (77.8%) (P less than
      0.05). In the FK-treated group, no difference in survival was observed between
      CMV-positive or CMV-negative cases at 1 year. Of the patients on CsA, 20%
      received OKT3 for persistent rejection, as compared with 13% in the FK-treated
      group. The patients receiving both CsA and OKT3 had a higher rate of upper
      gastrointestinal CMV infection than did FK-treated patients who also received
      OKT3 therapy (38.5% versus 20%, respectively). Based upon these data, it can be
      concluded that (1) patients receiving FK have a lower incidence of enteric CMV
      infection; (2) following OLTx, upper gastrointestinal CMV infection presents
      later in FK-treated patients; (3) the stomach is the most frequently involved
      organ in the UGIT; (4) FK-treated liver recipients have less severe enteric CMV
      infection than do CsA-treated patients; (5) enteric CMV is not a major cause of
      mortality in liver transplant recipients; and (6) in patients receiving FK, those
      who require OKT3 therapy do not appear to be at a greater risk for the
      development of CMV enteritis than those who do not.

PMID- 1373537
TI  - The in vitro immunosuppressive effect of deoxymethylspergualin in man as compared
      with FK506 and cyclosporine.
AB  - The effect of deoxymethylspergualin (MeDSG) on in vitro human lymphocyte response
      was assessed in comparison with FK506 and cyclosporine. Peripheral blood
      mononuclear cells from normal human volunteers were used for assay of mixed
      lymphocyte reaction, cell mediated lympholysis, and blastogenesis by PHA, IL-2,
      and OKT3. MeDSG suppressed only allogeneic stimulation (MLR and CML) and IL-2
      induced blastogenesis, not PHA- or OKT3-induced blastogenesis, although the other
      immunosuppressive agents showed some suppressive effect for all assays. A kinetic
      study of MLR showed that the suppressive activity did not decrease even when
      MeDSG was added at day 3 or day 4. The other agents, however, showed a weak
      suppressive effect when added at a later phase of MLR.

PMID- 1373538
TI  - QT prolongation and Torsades de Pointes after administration of FK506.

PMID- 1373539
TI  - Stimulation of liver regeneration by pretreatment with azathioprine as well as
      cyclosporine and FK506.

PMID- 1373540
TI  - Nonisotopic SSCP detection in PCR products by ethidium bromide staining.

PMID- 1373541
TI  - Expression of human decay accelerating factor or membrane cofactor protein genes
      on mouse cells inhibits lysis by human complement.

PMID- 1373542
TI  - Cytoprotective effect of CD59 antigen on xenotransplantation immunity.

PMID- 1373543
TI  - Synergism of splenectomy and immunosuppressive drugs in prolongation of cardiac
      xenograft survival.

PMID- 1373544
TI  - Preformed antibodies binding to endothelial targets are different from those
      binding to epithelial targets in discordant kidney xenotransplantation.

PMID- 1373545
TI  - The histopathologic appearance of rejected xenografts in a neovascularized and
      primarily vascularized rodent system.

PMID- 1373546
TI  - Immunosuppressive effect in combination therapy of cyclosporine A, FK 506, and 15
      deoxyspergualin on pancreatic islet xenotransplantation.

PMID- 1373547
TI  - Liver transplantation for diethylnitrosamine-induced hepatocellular carcinoma in
      rats.

PMID- 1373548
TI  - Langerhans cells in the lymph node: mirror section and immunoelectron microscopic
      studies.
AB  - Cells immunostained with antibodies against both OKT-6 and S-100 protein were
      observed only in superficial and hilar lymph nodes draining tissues with
      predominantly squamous epithelia. In contrast, in mesenteric lymph nodes and the
      spleen, only S-100 protein-positive, but OKT-6-negative cells were found. We
      suspect that the S-100 and OKT-6-positive cells might be Langerhans cells (LC)
      and the S-100-positive, OKT-6-negative cells, interdigitating reticulum cells
      (IDC). We further postulate that the LC in superficial and hilar lymph nodes
      might migrate from squamous epithelia, with which contact is required for the
      formation of Birbeck granules.

PMID- 1373549
TI  - Synthetic peptides and anti-peptide antibodies as probes to study interdomain
      interactions involved in virus assembly: the envelope of the human
      immunodeficiency virus (HIV-1).
AB  - Synthetic peptides and anti-peptide antibodies have been widely used as probes to
      map B- and T-cell epitopes on proteins. Such probes also have the potential to
      delineate contact sites involved generally in protein-protein interactions or in
      association of domains within a protein. We applied peptide/anti-peptide probes
      to define: (1) regions on the human immunodeficiency virus type 1 (HIV-1)
      envelope glycoproteins gp120 and gp41 involved in the association between these
      two glycoproteins; and (2) sites on gp120/gp41, essential for the association of
      HIV-1 with the CD4 cell receptor. Results of this examination suggested the
      following: (1) two segments on gp120, encompassing residues (102-126) and (425
      452), contribute to the binding site for CD4 and are expected to be juxtaposed in
      the folded gp120 chain; (2) portions of immunodominant gp120 and gp41 epitopes,
      encompassing residues (303-338) and (579-611), respectively, appeared to be
      involved in the gp120-gp41 association, as suggested by direct binding studies
      and by the limited accessibility of these epitopes on HIV-1 virions: other
      portions of gp120 also appeared to contribute to the association between these
      two glycoproteins; (3) there is a partial overlap between gp41 and CD4 binding
      sites on gp120; (4) the fusion domain and a segment (637-666) of gp41 are not
      accessible to antibodies after oligomerization of gp41; and 5) the gp120-gp41
      association was blocked by aurintricarboxylic acid, suggesting the possibility of
      developing antiviral compounds interfering with HIV-1 assembly.

PMID- 1373550
TI  - Expression of authentic vaccinia virus-specific and inserted viral and cellular
      genes under control of an early vaccinia virus promoter is regulated post
      transcriptionally in interferon-treated chick embryo fibroblasts.
AB  - The interferon sensitivity of the expression of an influenza-virus hemagglutinin
      (HA) gene cloned into the thymidine kinase (TK) gene of vaccinia virus was
      studied in chick embryo fibroblasts (CEF) and Madin-Darby bovine kidney (MDBK)
      cells. In CEF, the expression of the HA gene is inhibited by pretreatment of
      cells with homologous interferon. In MDBK cells, on the other hand, expression of
      the HA is not impaired by pretreatment with human interferon-alpha, and the
      synthesis of early vaccinia virus enzymes was also unaffected. These results
      indicate that the interferon sensitivity of HA gene expression is at least in
      part controlled by flanking regions of vaccinia virus DNA. In this report, we
      also address the question whether the expression of an influenza virus HA gene
      and the human histone H1 zero gene under control of a vaccinia virus immediate
      early promoter is affected in interferon-treated CEF by a post-transcriptional
      mechanism in the same way as the expression of the viral TK gene. In interferon
      treated cells mRNA synthesis specific for all these genes was enhanced. Steady
      state mRNA levels 6 hr p.i. were, however, lower than the amounts expected from
      the rate of mRNA synthesis during the first 6 hr p.i., suggesting that part of
      the viral RNA was degraded. Degradation resistant mRNA accumulated in the
      interferon-treated cells in an amount comparable to that found in infected CEF.
      This RNA could be translated into viral protein in a cell-free system. Therefore
      the degradation of viral mRNA cannot solely be responsible for the inhibition of
      viral protein synthesis in interferon-treated cells.

PMID- 1373551
TI  - Monoclonal IgM antibodies from cytomegalovirus-infected mice recognize the GlcNAc
      containing receptor determinant of murine CMV as well as neutralizing anti-CMV
      IgG antibodies.
AB  - This study examines monoclonal antibodies derived from mice at different time
      points after infection with attenuated murine cytomegalovirus (MCMV). The
      antibodies obtained from mice at 3 weeks p.i. were of IgG type (designated V
      antibodies) and several could neutralize the virus. Those obtained at 5 weeks
      p.i. were of the IgM class (designated R-antibodies), bound to uninfected (MEF,
      mouse embryo fibroblast) cells, and thereby blocked MCMV plaque formation. In
      ELISA, the IgM monoclonals (R-antibodies) bound to GalB1-3GlcNAc and GalB1
      4GlcNAc, the receptor determinants for MCMV. Similarly, these GlcNAc-containing
      residues blocked the binding of purified IgM monoclonal antibodies (MAbs) to MEF.
      The R- and V-series of antibodies showed mutual binding activities; for example,
      IgM MAb R-2D8 bound specifically to four (V-8C4, V-1C7, V-8C7, V-9C5) of six
      neutralizing IgG MAbs in ELISA. The same neutralizing IgG MAbs bound to
      antireceptor IgM antibodies in an immunoblot assay. This suggests that the IgM
      monoclonals directed against the known cell surface receptor determinant are anti
      idiotypic antibodies against neutralizing antiviral IgG antibodies. The
      neutralizing antiviral IgG MAbs bound to 60- and 66-kDa MCMV polypeptides on
      Western blots, suggesting that these viral polypeptides may be important in MCMV
      binding to this receptor. The R-series might represent anti-idiotype antibodies
      capable of down-regulating antiviral V-antibodies and may also represent a
      mechanism for the induction of IgM autoantibodies directed at cell surface
      glycolipids present in autoimmune CMV-associated neuropathies.

PMID- 1373552
TI  - Antigenic structure of transmissible gastroenteritis virus nucleoprotein.
AB  - A group of 11 monoclonal antibodies (MAbs) raised against transmissible
      gastroenteritis virus (TGEV) was used to study the antigenic structure of the
      virus nucleoprotein (N). To identify the regions recognized by MAbs, DNA
      fragments derived from the N-coding region of the TGEV strain FS772/70 were
      cloned into pUR expression plasmids and the antigenicity of the resulting fusion
      proteins was analyzed by immunoblotting. A major antigenic domain was identified,
      covering the first 241 amino acid residues of N, within which an epitope
      (residues 57-117) was also found. A second antigenic domain extended from
      residues 175 to 360 of the nucleoprotein, within which a subsite was
      characterized within the region covering residues 241-349. MAb DA3 recognized a
      linear epitope which mapped within residues 360 and 382 at the carboxy terminus
      of the nucleoprotein. The binding of the majority of the MAbs (8 out of 11) to
      large fusions, but not to smaller fragments included in them, suggests a
      conformational dependence of the MAb binding sites. Our data show that the use of
      fusions in Western blot experiments is a useful approach to map not only linear
      epitopes but more complex antigenic structures found in the nucleoprotein of the
      TGEV.

PMID- 1373553
TI  - Mechanism of interferon action: cDNA structure, expression, and regulation of the
      interferon-induced, RNA-dependent P1/eIF-2 alpha protein kinase from human cells.
AB  - A molecular cDNA clone (P1 KIN) was isolated that encodes the human RNA-dependent
      P1/eIF-2 alpha protein kinase. The complete cDNA sequence of the P1 KIN cDNA was
      determined; the longest open reading frame (ORF) encoded a 551 amino acid protein
      with a deduced molecular weight of 62055 Da. Transcripts prepared from the P1 KIN
      cDNA by transcription in vitro with T7 RNA polymerase programmed the cell-free
      synthesis of a protein indistinguishable by immunoprecipitation and immunoblot
      gel analyses from the authentic 67-kDa P1 protein synthesized in human U cells
      treated with interferon (IFN). Furthermore, by use of a sensitive primer
      extension assay with T7 DNA polymerase, the major site of translation initiation
      within the deduced ORF of the P1 KIN cDNA was directly identified. Northern RNA
      gel-blot analysis revealed that the P1 KIN cDNA strongly hybridized to two IFN
      induced mRNAs present in both human amnion U cells and HeLa cells; their sizes
      were 2.5 and 6 kb. Both transcripts were efficiently induced by IFN-alpha, but
      poorly by IFN-gamma. Polyclonal antibody was prepared against the product of the
      P1 KIN cDNA expressed in Escherichia coli. In Western blot analysis the antibody
      recognized a 67-kDa protein induced in human cells by IFN-alpha and, in addition,
      a 90-kDa protein whose level was not greatly altered by IFN treatment. The IFN
      induced 67-kDa protein was found associated with the ribosomal salt-wash fraction
      of IFN-treated human cells, whereas the 90-kDa protein was predominantly in the
      S100 soluble fraction. The time course for the induction by IFN-alpha of RNA
      dependent protein P1 kinase activity measured by immunoprecipitation was
      comparable to the time course for protein P1 induction measured by Western
      immunoblot analysis. The amino acid sequence of P1/eIF-2 alpha protein kinase
      deduced from the cDNA was 62% identical with the 518-residue murine TIK kinase
      and contained, within the carboxy-terminal half of the protein, the motifs
      commonly conserved among protein-serine/threonine kinases. The amino-terminal
      half of the P1 protein did not possess conserved kinase motifs, but did show
      extensive homology with vaccinia virus-predicted protein E3L.

PMID- 1373554
TI  - Mechanism of interferon action: identification of a RNA binding domain within the
      N-terminal region of the human RNA-dependent P1/eIF-2 alpha protein kinase.
AB  - A molecular cDNA clone of the human RNA-dependent P1/eIF-2 alpha protein kinase
      was expressed in Escherichia coli. Mutant P1 proteins were examined for RNA
      binding activity by Northwestern blot analysis using the reovirus s1 mRNA, an
      activator of the kinase; the adenovirus VAI RNA, an inhibitor of kinase
      activation; or human immunodeficiency virus (HIV) TAR RNA as probe. Analysis of
      TrpE-P1 deletion mutant fusion proteins revealed that the 11-kDa N-terminal
      region of the P1 protein bound reovirus s1 mRNA, adenovirus VAI RNA, and HIV TAR
      RNA. Neither s1 RNA, VAI RNA, nor TAR RNA was bound by truncated P1 proteins
      which lacked the N-terminal 98 amino acids. Computer analysis revealed that the
      human protein P1 sequence corresponding to amino acid residues within the N
      terminal RNA binding domain displays high homology (greater than 54% identity; 61
      to 94% similarity) with two animal virus proteins which possess RNA binding
      activity (vaccinia virus E3L; rotavirus VP2) and two proteins of unknown function
      (murine TIK; rotavirus NS34), but which are likely RNA binding proteins.

PMID- 1373555
TI  - Sequence analysis of human coronavirus 229E mRNAs 4 and 5: evidence for
      polymorphism and homology with myelin basic protein.
AB  - Human coronaviruses (HCV) are important pathogens responsible for respiratory,
      gastrointestinal and possibly neurological disorders. To better understand the
      molecular biology of the prototype HCV-229E strain, the nucleotide sequence of
      the 5'-unique regions of mRNAs 4 and 5 were determined from cloned cDNAs.
      Sequence analysis of the cDNAs synthesized from mRNA 4 revealed a major
      difference with previously published results. However, polymerase chain reaction
      amplification of this region showed that the sequenced cDNAs were produced from
      minor RNA species, an indication of possible genetic polymorphism in this region
      of the viral genome. The mutated messenger RNA 4 contains two ORFs: (1) ORF4a
      consisting of 132 nucleotides which potentially encodes a 44-amino acid
      polypeptide of 4653 Da; this coding sequence is preceded by a consensus
      transcriptional initiation sequence, CUAAACU, similar to the ones found upstream
      of the N and M genes; (2) ORF4b of 249 nucleotides potentially encoding an 83
      amino acid basic and leucine-rich polypeptide of 9550 Da. On the other hand, mRNA
      5 contains one single ORF of 231 nucleotides which could encode a 77-amino acid
      basic and leucine-rich polypeptide of 9046 Da. This putative protein presents a
      significant degree of amino acid homology (33%) with its counterpart found in
      transmissible gastroenteritis coronavirus (TGEV). The proteins in the two
      different viruses exhibit similar molecular weights and are extremely
      hydrophobic. Interestingly, a sequence homology of five amino acids was found
      between the protein encoded by ORF4b of HCV-229E and an immunologically important
      region of human myelin basic protein.

PMID- 1373556
TI  - Characterization of the endogenous reverse transcriptase reaction products of
      SIVagmTYO-7, a simian immunodeficiency virus isolated from an African green
      monkey.
AB  - The products of the endogenous reverse transcriptase reaction of SIVagmTYO-7 were
      characterized after the reaction conditions had been optimized. The major
      reaction product in the presence of actinomycin D and oligo(dT) was a DNA with a
      size of 300 bases. Without actinomycin D two additional reaction products with
      600 or 700 bases appeared. The 300 base product was identified as the (-)strong
      stop DNA, whereas the 700 base product is the (+)strong-stop DNA. The 600 base
      product appeared only after oligo(dT) priming. The (-)strong-stop DNA hybridized
      specifically with a 9 kb RNA found in virus particles and three RNA species of
      1.8, 4.8 and 9 kb isolated from SIVagmTYO-7 infected cells.

PMID- 1373557
TI  - Bioreagents in allograft immunosuppression.

PMID- 1373558
TI  - Abnormalities in immune regulation precede the development of multiple myeloma.
AB  - Immunosuppression of immunoglobulin synthesis seen in patients with multiple
      myeloma is in part due to immunosuppressive CD5 positive B cells. In a 13 year
      longitudinal study of an IgA-deficient blood donor who developed multiple
      myeloma, the presence of immunosuppressive CD5 positive B cells and T cells
      preceded the diagnosis of overt multiple myeloma and the appearance of
      immunosuppressive monocytes. These data argue that certain immune defects may be
      involved in the development of myeloma and are not simply a consequence of overt
      malignancy.

PMID- 1373559
TI  - Successful treatment of T-gamma lymphoproliferative disease with human
      recombinant granulocyte colony stimulating factor.
AB  - A trial of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was
      attempted in a male with agranulocytosis, infection, and T-gamma
      lymphoproliferative disease (T-gamma-LPD). During five days of rhG-CSF (960
      micrograms/day), the absolute neutrophil count (ANC) increased from 0.0 to 4.5
      K/microliters. There were no changes in eosinophil or lymphocyte counts. In
      addition, there was no toxicity. Bone marrow cytotoxic/suppressor cells
      (CD57+/CD8+) were elevated (21.9%) before and decreased to 10.6% (normal less
      than 12%) following rhG-CSF. By contrast, there was no change in activated T
      cells (CD3+DR+) or T cell gene rearrangements. These findings suggest rhG-CSF can
      improve granulopoiesis in T-gamma-LPD, possibly by altering T-cell mediated
      marrow suppression.

PMID- 1373560
TI  - Successful treatment of methimazole-induced agranulocytosis by granulocyte colony
      stimulating factor.

PMID- 1373561
TI  - Stretch-activated single-channel and whole cell currents in vascular smooth
      muscle cells.
AB  - Mechanosensitive ion channels may play a key role in transducing vascular smooth
      muscle (VSM) stretch into active force development. To test this hypothesis, we
      recorded single-channel and macroscopic currents during mechanical stimulation of
      enzymatically dispersed vascular smooth muscle cells. Patch pipette suction
      activated a nonselective cation channel that was permeable to K+, Na+, and Ca2+.
      Whole cell stretch was accomplished using two patch-type micropipettes attached
      to the cell ends with suction. Stretch elicited a sustained depolarization with a
      magnitude similar to that observed in pressurized arteries. Under whole cell
      voltage clamp, stretch activated an inward current with a reversal potential near
      -15 mV. In another series of experiments, whole cell stretch failed to modify the
      current-voltage relationship for voltage-gated calcium currents. Thus, in VSM,
      both single-channel and whole cell data are consistent with activation of a
      nonselective cation channel by stretch. This mechanism may, in part, account for
      pressure-induced activation of intact blood vessels.

PMID- 1373562
TI  - Endothelin stimulates protein synthesis in smooth muscle cells.
AB  - The present work was carried out to assess the effect of endothelin on the
      relative synthesis of protein, RNA, and DNA in confluent rat aortic smooth muscle
      cells (SMC) derived from Wistar-Kyoto (WKY) rats maintained under serum-free
      medium in the presence or absence of insulin, transferrin, and selenium. Insulin
      stimulated protein synthesis by 42%. Endothelin (1 x 10(-7) M) rapidly induced
      protein synthesis by 22% (-insulin) and 30% (+insulin). Prior treatment of SMC
      for 4 h with endothelin resulted in 50% (-insulin) and 38% (+insulin) increase in
      protein synthesis. The stimulatory effect of endothelin on protein synthesis
      could be partially blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a
      protein kinase C inhibitor. Atrial natriuretic factor had no effect on either the
      basal protein synthesis or protein synthesis stimulated by endothelin.
      Furthermore, endothelin stimulated RNA synthesis by twofold but had no effect on
      DNA synthesis in SMC derived from WKY rats. In contrast, SMC derived from
      spontaneously hypertensive rats showed increased DNA synthesis and cell growth
      after endothelin stimulation. These studies show that this hormone may play a
      pivotal role in the development of vascular hypertrophy in hypertension.

PMID- 1373563
TI  - Gonadotropin and cAMP modulation of IGE binding protein production in ovarian
      granulosa cells.
AB  - Porcine granulosa cells (GC) produce insulin-like growth factor (IGF) binding
      protein (BP)-3 and IGFBP-2 in culture. A gonadotropin, follicle-stimulating
      hormone (FSH), dramatically inhibited GC production of these IGFBPs in control
      cultures and in cultures stimulated by insulin plus epidermal growth factor (EGF)
      or IGF-I plus EGF. Stimulators of adenylate cyclase (forskolin, cholera toxin)
      and a derivative of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromoadenosine
      3',5'-cyclic monophosphate, inhibited IGFBP synthesis in a manner similar to FSH.
      In contrast, the antagonist of cAMP action, (R)-p-adenosine 3',5'-cyclic
      phosphorothioate [(R)-p-cAMPS], significantly stimulated production of IGFBP-3
      and IGFBP-2 compared with controls. This stimulatory effect of (R)-p-cAMPS was
      counteracted by cotreatment with FSH in a dose-dependent manner. Finally,
      treatment of GC cultures with FSH plus 3-isobutyl-1-methylxanthine resulted in a
      significant reduction in cellular content of mRNA coding for IGFBP-3 with no
      change in IGFBP-2 mRNA. In summary, agents that elevate intracellular cAMP were
      found to mimic the effects of FSH on IGFBP production.

PMID- 1373564
TI  - Atrial natriuretic peptide synthesis in atrial tumors of transgenic mice.
AB  - Transgenic mice harboring a chimeric gene linking mouse protamine 1 5'-flanking
      sequence to the coding sequence of the simian virus 40 T-antigen develop
      spontaneous rhabdomyosarcomas of the right atria. The presence of the tumors is
      accompanied by dramatic elevations in plasma atrial natriuretic peptide (ANP)
      immunoreactivity (1,698 +/- 993 vs. 60 +/- 18 fmol/ml for controls) and
      hematocrit (56 +/- 8 vs. 51 +/- 2 for controls). The immunoreactive ANP (irANP)
      present in the tumors is similar in size to irANP found in normal mouse atria.
      ANP mRNA transcripts present in the tumors also appear to be very similar in
      overall size and 5'-termini to those produced in normal cardiac tissue.
      Microscopically, the tumors are composed of a disorganized array of densely
      packed abnormal-appearing cells. Immunocytochemistry and in situ hybridization
      analysis reveal considerable heterogeneity in ANP gene expression. ANP peptide
      and mRNA are detectable throughout the parenchyma of the tumors, but absolute
      levels of expression vary widely among different cells in the population. These
      tumors represent a potentially valuable model for the study of inappropriate ANP
      secretion and may provide a tissue source for the development of an ANP-producing
      atrial cell line.

PMID- 1373565
TI  - Neutrophil accumulation in ischemic reperfused rat liver: evidence for a role for
      superoxide free radicals.
AB  - Oxygen-derived free radicals and leukocytes have been implicated in the
      pathogenesis of ischemia-reperfusion injury. This study aimed at determining, by
      using biochemical and histochemical techniques, whether an accumulation of
      neutrophils occurs in the ischemic reperfused rat liver and whether superoxide
      free radicals play a role in mediating this neutrophil accumulation. Hepatic
      ischemia was induced by occluding blood supply to the left and median lobes, and
      reperfusion was reinstituted by releasing the occlusion. Myeloperoxidase activity
      of the liver was measured with a tetramethylbenzidine-H2O2 assay after removal of
      glutathione (by dialysis) and in the presence of 3-aminotriazole (catalase
      inhibitor). A modification of Graham and Karnovsky's method was used to stain
      neutrophils in liver frozen sections, and the number of neutrophils was counted.
      Results showed that ischemia-reperfusion of the liver produced a 4.4-fold
      increase in myeloperoxidase activity (from 0.073 +/- 0.009 to 0.320 +/- 0.017
      units/mg liver, means +/- SE), which was proportional to the number of
      neutrophils (3.1-fold increase from 18 +/- 7 to 57 +/- 4 cells/mm2) in the liver
      tissue. Pretreatment with long-acting superoxide dismutase significantly
      attenuated the elevated myeloperoxidase activity and the number of neutrophils.
      These results indicate that reperfusion after a period of ischemia induces an
      accumulation of neutrophils in the liver, and superoxide anion free radicals are
      important mediators in the mechanism of this neutrophil accumulation.

PMID- 1373566
TI  - Characterization of high-conductance anion channels in rat bile duct epithelial
      cells.
AB  - We have utilized patch clamp recording techniques to identify a high-conductance
      anion channel in the plasma membrane of rat bile duct epithelial cells. Cells
      were isolated from the intrahepatic bile duct 2-6 wk after bile duct ligation.
      Channels were present in 27% (28/102) of excised patches, and, with 150 mM Cl- in
      bath and pipette solutions, the slope conductance of the fully open level was
      approximately 364 +/- 18 pS (n = 8) with current reversal = 0 +/- 1 mV. Channel
      characteristics were not affected by substitution of K+ for Na+ in the pipette
      solution; but substitution of HCO3-, gluconate, or increased NaCl caused a shift
      in the reversal potential toward the new equilibrium potential for Cl-. The
      permeability ratios were PHCO3-/PCl- = 0.51 +/- 0.03 (n = 5), Pgluconate/PCl- =
      0.12 +/- 0.04 (n = 7), and PNa+/PCl- = 0.11 +/- 0.02 (n = 3). Current transitions
      to a subconductance level at 72% of the fully open level were present in most
      studies. Channel open probability was greatest near 0 mV and decreased rapidly
      outside of -20 to +20 mV because of voltage-dependent channel closure. The time
      course for current relaxation of summed single channel currents could be
      described by a single exponential with more rapid channel closure as the
      magnitude of the voltage step away from 0 mV increased. In the cell-attached
      configuration, the channel was rarely open (4/35, 11%) but opening could be
      induced by negative pipette pressure (5/14, 35%). Possible physiological roles
      for this channel are discussed.

PMID- 1373567
TI  - Amylase release from streptolysin O permeabilized fetal pancreatic acini.
AB  - Developmental regulation of Ca(2+)-dependent protein discharge was investigated
      in fetal and neonatal rat pancreatic acini permeabilized with streptolysin O.
      When incubated at 37 degrees C in a Ca(2+)-ethylene glycol-bis(beta-aminoethyl
      ether)-N,N,N',N'-tetraacetic acid/K glutamate buffer, permeabilized day 19 and 20
      fetal acini demonstrated Ca(2+)-dependent release of amylase, whereas day 21
      (term) fetal acini did not. Ca(2+)-dependent amylase release reappeared in day 1,
      2, and 6 neonatal pancreases. ATP depletion completely inhibited Ca(2+)
      stimulated amylase release from both day 20 fetal and adult acini. Ca(2+)
      dependent amylase discharge from day 20 fetal acini was enhanced by the
      nonhydrolyzable GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S),
      and by the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA). Ca(2+)
      independent GTP gamma S-stimulated amylase release was observed from adult but
      not from day 20 fetal acini. In contrast to its stimulatory effects in
      permeabilized adult acini, adenosine 3',5'-cyclic monophosphate (cAMP) alone had
      little effect on release from permeabilized day 20 fetal acini. Our studies
      indicate that the fetal pancreas is competent to undergo Ca(2+)-dependent protein
      secretion but that this secretion is suppressed at birth. Our studies also
      suggest that the fetal gland is sensitive to modulators of exocytosis active in
      the adult pancreas, such as GTP gamma S, TPA, and cAMP but responds differently
      to these agents compared with responses in adult glands.

PMID- 1373568
TI  - Role of cholecystokinin in induction and maintenance of dietary protein
      stimulated pancreatic growth.
AB  - The role of cholecystokinin (CCK) in induction and maintenance of pancreatic
      growth stimulated by a high-protein diet was investigated. Rats adapted to 5%
      casein diet were switched to 70% casein for 21 days. MK-329, a CCK receptor
      antagonist, was administered at 2.5 mg.kg-1.day-1 ip, beginning on day zero (day
      zero treatment) or day 7 (midcourse treatment) of feeding 70% casein and
      thereafter. Another group was returned to 5% casein after 7 days of feeding 70%
      casein. Feeding 70% casein significantly stimulated increases of 32, 87, 74, 216,
      and 1,450% in pancreatic DNA, RNA, wet weight, protein content, and chymotrypsin
      content, respectively. Midcourse treatment with MK-329 was more effective than
      day zero treatment, and it completely reversed increases in pancreatic weight and
      RNA content, partially reversed increases in protein and chymotrypsin content,
      and had no effect on DNA content. Return to 5% casein rapidly reversed increases
      in pancreatic parameters, except for DNA. The results indicate that CCK is
      essential for induction and maintenance of dietary protein-stimulated pancreatic
      hypertrophy.

PMID- 1373569
TI  - Bleomycin stimulation of cytokine secretion by the human alveolar macrophage.
AB  - Bleomycin (BLM) is a very effective antineoplastic drug for many gynecologic and
      urinary tract carcinomas. However, its use, e.g., cumulative dosage, often is
      limited by the pulmonary fibrosis that it causes. The mechanism by which BLM
      causes fibrosis is not understood but is proposed to involve the pulmonary
      macrophage, a central cell in the cytokine network of the lung. To examine the
      direct effects of this drug on the human alveolar macrophage, we have treated
      human alveolar macrophages (isolated from normal subjects by bronchoalveolar
      lavage) with BLM in vitro and examined resultant macrophage secretory products
      that have importance for inflammatory and fibrotic processes. A 24-h treatment
      with BLM (0.5-100 mU/ml) was found to result in 1) a concentration-dependent
      decrease in the ability of the macrophage to produce superoxide anion in response
      to phorbol 12,13-dibutyrate, 2) an increase in secreted interleukin-1 beta (IL-1
      beta), and 3) a decrease in intracellular levels of adenosine 3',5'-cyclic
      monophosphate. Kinetic studies revealed a time-dependent appearance of BLM
      induced cytokines; tumor necrosis factor-alpha could be detected as early as 4 h
      after stimulation, followed by IL-1 beta at 8 h. The secretion of these cytokines
      was found to precede the release of prostaglandin E2, which became significant
      only at 24 h. Taken together, the present results imply that the human alveolar
      macrophage does not contribute to BLM-induced oxidant injury of the lung but that
      it may contribute to the development of BLM-induced pulmonary fibrosis.

PMID- 1373571
TI  - Calcium imaging of mechanically induced fluxes in tissue-cultured chick heart:
      role of stretch-activated ion channels.
AB  - Heart rate and contractility are sensitive to stretch. To better understand the
      origin of these effects, we have studied the effect of mechanical stimuli on a
      model system of tissue-cultured heart cells. Gently prodding cells with a pipette
      produced a Ca2+ influx that often led to waves of calcium-induced calcium release
      (CICR) spreading from the site of stimulation. Ca2+ release could also be
      produced by pulling on neighboring cells. The response was blocked by removing
      extracellular Ca2+ or by adding 20 microM Gd3+ to normal saline. The mechanical
      sensitivity probably arose from stretch-activated ion channels (SACs) based on
      several lines of evidence. Chick heart cells contain nonselective cation SACs
      that pass Ca2+ as well as Na+ and K+. Both the SACs and the fluorescence response
      are blocked by 20 microM Gd3+. Removal of Ca2+ from the extracellular medium
      blocked the fluorescent response. Cultures without SACs (grown in the absence of
      embryo extract) had no mechanically induced fluxes. These data contradict the
      recent claim that SAC activity is a patch-clamp artifact (C.E. Morris and R.
      Horn, Science Wash. DC 256: 1246-1249, 1991). The SACs had a density of
      approximately 1/micron 2 and were expected to pass less than 20 fA of Ca2+
      current under physiological conditions. The change in intracellular concentration
      of Ca2+ ([Ca2+]i) resulting from activation of SACs may be too small to induce
      CICR unless the channels pass current into a restricted space (N. LeBlanc and
      J.R. Hume, Science Wash. DC 248: 372, 1990).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373570
TI  - Expression of CFTR and presence of cAMP-mediated fluid secretion in human fetal
      lung.
AB  - We studied the developmental expression of the cystic fibrosis (CF) gene in human
      lung tissue from normal and CF-affected fetuses. Two unrelated CF fetuses, both
      homozygous for the delta F508 deletion, were examined. Cystic fibrosis
      transmembrane conductance regulator (CFTR) mRNA was present in second-trimester
      CF lung and in first- and second-trimester normal lung as assessed by
      amplification of reverse transcribed total RNA with the use of the polymerase
      chain reaction. CFTR protein was identified by immunoprecipitation in normal
      second-trimester fetal lung explants. To evaluate possible functional
      consequences of CF in the fetus, lung tissue explants were grown in submersion
      organ culture. By light and electron microscopy, the CF fetal lung explants
      appeared normal. When explants from normal fetal lung were exposed to 8-(4
      chlorophenylthio) adenosine 3',-5'cyclic monophosphate (CPT-cAMP), and 3-isobutyl
      1-methylxanthine (IBMX) for 24 h, the intraluminal fluid content increased, as
      assessed by a 40 +/- 4% increase in cross-sectional diameter. In contrast,
      identically treated CF explants showed no significant change in explant diameter
      (3 +/- 1.6%). The transepithelial potential (psi t) across fetal lung explants
      was measured with microelectrodes. In normal second-trimester explants, CPT-cAMP
      and IBMX caused hyperpolarization of psi t (-0.93 +/- 14 mV to -4.3 +/- 1.2 mV);
      in contrast, CF fetal lung explants showed no significant change in psi t with
      CPT-cAMP and IBMX (-0.84 +/- 0.07 mV to -1.21 +/- 0.26 mV). This study confirms
      the presence of CFTR mRNA and protein in human fetal lung and suggests that
      although the CF fetal lung appears normal morphologically, there is a defect in
      cAMP-mediated fluid secretion in the lung of the CF fetus.

PMID- 1373572
TI  - A model of countercurrent shunting of oxygen in the intestinal villus.
AB  - This report describes a mathematical model of the countercurrent shunting (CCS)
      of O2 in the intestinal villus. The anatomic basis for the model is the close
      proximity of the arteriole and venule between which O2 is free to diffuse. The
      model divides the villus into four segments from base to tip. Steady-state
      equations describe the convective and diffusive fluxes of O2 in the arteriolar,
      capillary, and tissue compartments within each segment. Longitudinal diffusion
      along the length of the villus is assumed to be negligible. Simulations with the
      model led to the following observations: 1) CCS shifted the VO2 vs. blood flow
      curve down and to the right, slightly impairing VO2 at a given blood flow; 2) the
      base-to-tip PO2 gradient caused by the tissue O2 consumption was reduced by CCS;
      3) when blood flow was reduced, the base-to-tip PO2 gradient increased until the
      tip PO2 fell to zero and then fell with further flow reductions; 4) lowering
      blood flow initially caused slight increases in shunting but further decreases in
      flow reduced shunting; 5) in the blood flow range in which VO2 was flow
      independent, increasing the O2 demand or decreasing the intervascular distance
      increased shunting because of the greater arteriole-to-capillary O2 concentration
      gradient and the decreased diffusion distance, respectively; and 6) lowering the
      hemoglobin's P50 to simulate fetal blood caused slight reductions in shunting and
      reduced VO2 at a given flow. In summary, the model confirms the potentially
      deleterious effects of CCS on intestinal oxygenation, and, in contrast to
      assertions in the literature, it shows that a base-to-tip PO2 gradient is not
      prima facie evidence of counter-current shunting.

PMID- 1373573
TI  - Calcium currents in hearts with persistent truncus arteriosus.
AB  - We have used the neural crest model of defective heart development to
      characterize both L- and T-type Ca2+ currents (ICa,L and ICa,T) in ventricular
      myocytes from embryonic chick hearts with a severe outflow tract anomaly known as
      persistent truncus arteriosus (PTA). Because of smaller whole embryo weights but
      no significant change in the weights of ventricles with PTA, the ventricle to
      whole embryo weight ratios from hearts with PTA were 61% larger than normal at
      day 11 of incubation. There was a 51% reduction in the peak magnitude of ICa,L at
      a test potential of +10 mV (-1.4 vs. -0.7 microA/cm2), whereas ICa,T, a
      proportionately large fraction of the total Ca2+ current in the embryonic chick
      ventricle, was unaffected. In comparison to sham-operated controls, ICa,L was
      otherwise not different. Half-activation occurred at about -1 and -41 mV, whereas
      half-inactivation occurred at -19 and -61 mV for ICa,L and ICa,T, respectively.
      The time for half-recovery from inactivation were not different and were 200 and
      230 ms for ICa,L and ICa,T, respectively. The time for half-decay of the currents
      and their responses to BAY K 8644 were also similar in both sham-operated and
      experimental hearts. Although the dihydropyridine receptor binding experiments
      suggest that the total number of L-type Ca2+ channels was not different, the
      results from the physiological experiments indicate that the number of functional
      L-type channels available for opening and/or the single-channel conductance may
      be reduced in hearts with PTA. Finally, our results with the neural crest model
      indicate that it is unlikely that the development of Ca2+ currents is influenced
      by the onset of cholinergic innervation in the heart.

PMID- 1373574
TI  - Cardiac atrial natriuretic factor during evolution of congestive heart failure.
AB  - Congestive heart failure (CHF) is a pathophysiological condition associated with
      increased plasma levels of atrial natriuretic factor (ANF), a peptide hormone of
      cardiac origin that participates in the homeostatic control of intravascular
      volume and vascular tone. Atrial myocytes serve as the principal source of ANF
      under physiological conditions, although recent studies have demonstrated that
      ventricular myocardium may also synthesize ANF in models of CHF associated with
      ventricular hypertrophy. The current study was designed to investigate the roles
      of atrial and ventricular myocardium to synthesize, store, and release ANF during
      the evolution of tachycardia-induced CHF in the dog. The present study
      demonstrates a persistent elevation of plasma ANF during the evolution of CHF. In
      acute CHF (3 h), plasma ANF increased independent of cardiac ANF synthesis. In
      chronic CHF (15 and 30 days), plasma ANF is maintained by an increase in atrial
      synthesis and release of the peptide, without recruitment of ventricular ANF
      synthesis. The present study demonstrates that in acute CHF the increase in
      plasma ANF is regulated by release of stored peptide, and in chronic CHF the
      persistent elevation of plasma ANF is maintained by an increase in atrial
      synthesis of ANF.

PMID- 1373575
TI  - Dipyridamole-induced capillary growth in normal and hypertrophic hearts.
AB  - Chronic increases in myocardial blood flow have been shown to stimulate capillary
      proliferation in normal growing hearts. It is unknown, however, if elevated
      myocardial blood flow stimulates precapillary and/or capillary growth in hearts
      undergoing hypertrophy. Accordingly, renal hypertension was produced in rabbits
      (Page, 1-kidney, 1-wrap model) in which one group of Page (n = 9) and one group
      of normotensive sham (n = 10) rabbits were given dipyridamole (4.0 mg/kg sc)
      twice daily for 2 mo. Another group of Page (n = 7) and sham (n = 12) rabbits
      received vehicle injections. In separate acute studies performed on conscious
      rabbits, this does of dipyridamole increased myocardial blood flow 35-60% over
      time without altering transmural distribution of flow or systemic blood pressure.
      Two months later, minimal coronary vascular resistance (MCVR/100 g) was
      calculated from perfusion during maximal coronary vasodilation in conscious
      animals. Histomorphometric methods were then utilized to evaluate various indexes
      of capillarity in perfuse-fixed hearts. Systolic pressure and left ventricle
      weight-to-body weight ratios were significantly higher in Page vs. sham rabbits;
      dipyridamole treatment did not alter these parameters within either group.
      Similarly, dipyridamole treatment did not significantly alter MCVR/100 g values
      in either normotensive or hypertensive rabbits. In contrast, dipyridamole
      treatment increased endomyocardial capillary length density by 33% in the
      hypertensive group (P less than 0.05) and 11% in the sham group (P not
      significant) compared with the respective vehicle-treated rabbits. In addition,
      intercapillary distance was significantly reduced in the endomyocardial region of
      both groups receiving dipyridamole injections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373576
TI  - CCK-receptor antagonists attenuate suppression of sham feeding by intestinal
      nutrients.
AB  - To test the possibility that endogenous cholecystokinin (CCK) participates in
      suppression of sham feeding by intraintestinal nutrient infusions, we examined
      the effect of CCK-receptor antagonists on the suppression of sham feeding by
      intraintestinally infused oleic acid, maltose or L-phenylalanine (L-Phe). In
      addition, we monitored amylase activity in the intestinal lumen during some sham
      feeding experiments and measured plasma CCK in parallel experiments using
      intestinally infused animals that were not feeding. Suppression of sham feeding
      by oleic acid or maltose was attenuated by CCK-receptor antagonists, while
      suppression of sham feeding by L-Phe was not. Oleate infusion increased plasma
      CCK concentration and luminal amylase activity. Oleate-induced increase in
      luminal amylase activity was attenuated by a CCK-receptor antagonist.
      Intraintestinal maltose or L-Phe did not increase plasma CCK concentration or
      luminal amylase activity, suggesting that they did not release endocrine CCK.
      These results suggest 1) that endogenous CCK mediates suppression of sham feeding
      by oleate and maltose but not by L-Phe and 2) that CCK participating in
      suppression of feeding by intestinal stimuli might not be of endocrine origin.

PMID- 1373577
TI  - Evaluation of radical prostatectomy specimens. A comparative analysis of sampling
      methods.
AB  - We evaluated 104 radical prostatectomies for clinical stage B (n = 93) and stage
      A (n = 11) prostate cancer. Seven (8%) stage B cases had no gross cancer. By
      submitting only gross stage B cancer along with standard sections of proximal and
      distal margins, base of seminal vesicles, and most apical section (next to distal
      margin), we identified 91% of capsular penetration and 96% of positive margins as
      compared with identification by complete microscopic examination. Although this
      method identified 100% capsular penetration and positive margins in stage A
      cases, 28% of all the cases were grossly normal. Stage A tumor was often
      difficult to identify because of its heterogeneous location, its gross similarity
      to nodular hyperplasia, and the confounding presence of post-transurethral
      resection scarring. In 98% of all stages B and A cases, this method identified to
      within 1, the Gleason sum of the totally embedded radical prostatectomy. Using
      this sampling method, key pathologic parameters were identified with an average
      of 13 blocks (range 7-36) as compared with totally embedding the prostate, using
      an average of 42 blocks (range 21-81). Based on our study and our understanding
      of stages A and B disease, we recommend that in grossly normal glands, alternate
      posterior sections (stage B) and alternate entire sections (stage A) be
      submitted. Use of this sampling method will achieve a greater uniformity in the
      processing of specimens and a more accurate pathologic analysis of radical
      prostatectomy specimens.

PMID- 1373578
TI  - Nephrogenic adenofibroma. A novel kidney tumor of young people.
AB  - Nephrogenic adenofibroma is a novel kidney tumor of young people (mean age of
      presentation, 13 years), who present with polycythemia, hypertension, or
      hematuria, which resolve following nephrectomy. The typical nephrectomy specimen
      contains a solitary, nonencapsulated, vaguely circumscribed, irregularly shaped
      or spherical, firm mass with either tan, gray-white, or pale yellow coloration.
      Cysts are sometimes present within the tumor. The histologic appearance is
      distinctive and characterized by a marked proliferation of spindled mesenchymal
      cells resembling the classical type of congenital mesoblastic nephroma, encasing
      discrete nodules of embryonal epithelium similar to the hyperplastic nephrogenic
      rests (nephroblastomatosis) usually associated with Wilms' tumor. The mesenchymal
      component consists of a fascicular proliferation of tightly interlaced, uniform,
      benign-appearing spindled cells that immunostatin for vimentin and fibronectin,
      but not desmin or actin. The epithelial component consists of discrete islands of
      blastemal cells that are partially or fully differentiated toward tubular,
      tubulopapillary, or papillary structures. Psammoma bodies are plentiful.
      Embryonal epithelium immunostains for cytokeratin but not epithelial membrane
      antigen. The overall histologic appearance of the mesenchymal and epithelial
      components is benign, and preliminary clinical data suggest that the tumor has a
      benevolent course. Two cases, however, contained small, well-circumscribed
      papillary lesions near the renal pelvis that resembled low-grade collecting duct
      carcinoma. The clinical implications of the latter finding are unclear.

PMID- 1373579
TI  - Primary vascular tumors of lymph nodes other than Kaposi's sarcoma. Analysis of
      39 cases and delineation of two new entities.
AB  - Primary vascular tumors of lymph nodes other than Kaposi's sarcoma are very rare,
      as attested to by only a handful of case reports in the literature. Based on an
      analysis of 39 such cases, we could distinguish five major groups. Hemangiomas of
      capillary/cavernous, lobular capillary, and cellular types were composed of
      compact aggregates of blood-filled vessels, variable in size, that replaced the
      nodal architecture partly or almost completely; some appeared to have originated
      in the hilum or medulla. These hemangiomas either represented incidental findings
      in lymph nodes or were seen with solitary lymph node enlargement; the evolution
      was benign with no recurrence. A distinctive benign lesion occurring exclusively
      in inguinal lymph nodes, which we propose designating "angiomyomatous hamartoma,"
      showed replacement of the nodal parenchyma by smooth muscle cells and fibrous
      tissue, in continuity with exuberant proliferation of muscular vessels in the
      hilum. Epithelioid vascular tumors, characterized by plump endothelial cells with
      dense eosinophilic cytoplasm and numerous vacuoles, exhibited a range of
      differentiation, from hemangioma with well-formed vascular channels (with or
      without tissue eosinophilia) to hemangioendotheliomas composed predominantly of
      cords and sheets of tumor cells lying in a hyaline-myxoid matrix. Epithelioid
      hemangioendothelioma was particularly likely to be mistaken for metastatic
      carcinoma, and local recurrence could occur. A variant, the spindle and
      epithelioid hemangioendothelioma, was characterized by the presence of an
      additional component of spindle cells. Another tumor we found, polymorphous
      hemangioendothelioma, is a previously uncharacterized borderline malignant
      vascular tumor exhibiting solid, primitive vascular and angiomatous patterns and
      relatively bland cytologic features. Lymphangiomas of lymph nodes usually showed
      simultaneous multifocal and extra-nodal involvement and were characterized by
      cystic endothelium-lined spaces filled predominantly with lymph fluid. It is
      important to recognize these primary vascular tumors of lymph nodes to avoid
      mistaking them for a variety of benign vasoproliferative lesions, Kaposi's
      sarcoma, angiosarcoma, and metastatic cancer.

PMID- 1373580
TI  - T-cell-rich B-cell lymphomas. A clinicopathologic study of 19 cases.
AB  - T-cell-rich B-cell lymphomas (TCRBCLs) are recently described, unusual non
      Hodgkin's lymphomas that have a diffuse morphology, a predominance of reactive T
      cells, and a minority of neoplastic B-cells. The clinical and pathological
      features of 19 TCRBCLs, all of which demonstrated B-cell clonality, are
      presented. These lymphomas generally affected older patients by widespread
      disease and usually were nodal in origin. Treatment varied, but continuous
      complete remissions (eight patients) were achieved only in those receiving
      chemotherapy directed at intermediate-grade lymphomas. Although morphologically
      heterogeneous, all cases resembled peripheral T-cell lymphomas (PTCLs); several
      TCRBCLs also contained Reed-Sternberg-like cells. Flow cytometry or frozen
      section immunoperoxidase failed to detect monotypic immunoglobulin (Ig) in eight
      of eight cases tested. In contrast, paraffin immunoperoxidase was very useful
      diagnostically, showing large L26 (CD20-associated) positive cells scattered
      singly or in small clusters among numerous small T-cells (UCHL1[CD45RO] positive)
      in all cases. Monotypic cytoplasmic Ig was present in 16 of 19 cases, one of
      which exhibited plasmacytic differentiation. Southern blot analysis demonstrated
      relatively faint Ig JH and/or JK bands, indicating a small monoclonal B-cell
      population in nine of 11 cases, one of which also showed a bcl-2 rearrangement.
      No T-cell receptor gene rearrangements were observed. These results showed that
      TCRBCLs may be easily confused with PTCLs or occasionally confused with Hodgkin's
      disease. TCRBCLs are probably heterogeneous biologically; some cases are of
      follicular center cell origin. These lymphomas respond to chemotherapy directed
      at intermediate-grade lymphomas, apparently have a better prognosis than PTCLs,
      and seem to represent morphological variants of different types of large B-cell
      lymphomas.

PMID- 1373581
TI  - Sclerosing adenosis of the prostate gland. A lesion showing myoepithelial
      differentiation.
AB  - Sclerosing adenosis of the prostate is a rare lesion characterized by the
      proliferation of variably sized glands in a cellular stroma. We report light
      microscopic, immunohistochemical, and ultrastructural studies in 22 examples from
      15 patients. Two cases were identified in 100 consecutive prostates embedded by a
      whole organ method, giving a prevalence of 2%. Antibodies directed against the
      following antigens were used: high-molecular-weight cytokeratin (CKH; 34 beta
      E12); cytokeratin (CK; AE1/AE3), prostatic acid phosphatase (PAP), prostate
      specific antigen (PSA), S-100 protein, muscle-specific actin (HHF35), and
      vimentin (Vim). Cells within the glandular component demonstrated positive
      reactivity for CK, CHH, PSA, and PAP, indicating a prostatic epithelial origin.
      In addition, a distinct population of cells reacting for muscle-specific actin
      and S-100 protein was identified within this glandular element. Adequate material
      for ultrastructural study was available in five cases; all showed the presence of
      flattened cells located between the basement membrane and secretory epithelial
      cells, which had features typical for myoepithelial differentiation. Although the
      prostate gland does not normally contain myoepithelial cells, we have documented
      their consistent presence in this unusual lesion; we believe these cells arise by
      a metaplastic process from the prostatic basal cells.

PMID- 1373582
TI  - Follicular neoplasms of the thyroid. Total circumferential evaluation of the
      fibrous capsule.
AB  - Fourteen encapsulated follicular neoplasms were extensively dissected without
      tangential sectioning to represent the circumference of the entire capsule on
      sequential histologic sections. A thorough evaluation of these sections divided
      the 14 cases into five benign adenomas, seven encapsulated carcinomas with only
      intracapsular angioinvasion, and two minimally invasive carcinomas with focal
      capsular invasion. Among these nine early-stage follicular carcinomas it was
      found that angioinvasion occurred multicentrically in at least seven and showed a
      geographically even distribution. Angioinvasion was found far more often than
      capsular invasion on the circumference of all nine early-stage carcinomas.
      Multiple sections produced by this extensive dissection aided the disclosure of
      minute but convincing findings of angioinvasion. Also, a fibrous capsule as thick
      as 3.8 mm at its maximum thickness as well as an irregular interface between the
      capsule and parenchyma were often found to be characteristic of these early-stage
      carcinomas. Thus, upon comparison with 38 previous cases of similarly localized
      follicular neoplasms, in which randomly sampled histologic sections yielded
      diagnoses of benign adenoma (21 cases) and encapsulated or minimally invasive
      carcinoma (17 cases), extensive circumferential evaluation of the capsule is
      considered to allow not only effective distinction of follicular neoplasm with
      slight invasive capability from benign adenoma but also adequate assessment of
      invasive foci with application of strict criteria. Despite the similarity of
      clinical prognosis among all the above adenomas and early-stage carcinomas, given
      the limited follow-up period, an extensive examination method introduced herein
      is practically useful and necessary for identification of malignancy in
      encapsulated follicular neoplasms.

PMID- 1373583
TI  - Desmoplastic trichilemmoma.
AB  - Seven cases of desmoplastic trichilemmoma (DT), a recently described
      pseudomalignant variant of trichilemmoma, are reviewed. The tumor generally
      occurs in men after the fifth decade of life and presents as a small solitary
      nodule on the face. It is frequently misdiagnosed clinically as a basal cell
      carcinoma or a papilloma. Histologically DT displays a superficial lobular growth
      arranged about a central prominent desmoplastic stroma. At the periphery, the
      tumor lobules show the typical features of trichilemmoma. In contrast, at the
      center the cells assume a more random pattern of cords and strands traversed by
      the hyaline stroma, mimicking invasive carcinoma. The tumor's architectural
      pattern, in particular the perilobular hyaline mantle, enables DT to be
      differentiated from basal cell carcinoma and malignant trichilemmoma.
      Immunohistochemical analysis failed to demonstrate human papilloma virus (HPV),
      epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and alpha
      lactalbumin in tumor epithelium. Keratin was expressed by the central
      pseudoinvasive epithelial cords. Neither factor XIIIa nor keratin expression was
      found in the stromal cells, which stained only for vimentin. These findings
      suggest that DT is not an HPV-induced epithelial proliferation and that the
      stroma is not the result of degenerative changes in tumor epithelium. Instead,
      there appears to be a fibroblast-mediated, dendrocyte-independent, stromal
      reaction producing this appearance.

PMID- 1373584
TI  - Distribution of cytokeratin polypeptides in syringomas. An immunohistochemical
      study on paraffin-embedded material.
AB  - The distribution of cytokeratin (CK) polypeptides expressed in syringomas (12
      cases) was compared with that in normal eccrine sweat ducts using
      immunohistochemical techniques on paraffin-embedded tissue. Intradermal and
      intraepidermal segments of the eccrine duct showed reactivity with an antibody to
      CK1/5/10/11 in all cell layers, whereas CK19 expression was restricted to the
      luminal cell layer. CK14 was expressed in all cells of the eccrine duct except
      for the peripheral cells of the intraepidermal duct. Expression of CK5/6 was seen
      in the basal cells of the dermal duct and of the lower intraepidermal duct (sweat
      duct ridge) exclusively. Reactivity with an antibody to CK1 was found in the
      intermediate cells of the uppermost part of the eccrine dermal duct. In addition,
      this antibody gave a strong staining of the peripheral cells of the
      intraepidermal duct, leaving basal cells of the sweat duct ridge and luminal
      cells unstained. In syringoma, CK distribution was essentially comparable with
      that found in the uppermost part of the dermal duct and in the sweat duct ridge.
      Namely, ductal luminal cells expressed CK1/5/10/11, CK19, and variably CK14.
      Intermediate cells of ductal structures and solid nests were homogeneously
      stained by antibodies to CK1 and CK1/5/10/11, whereas CK14 was expressed
      heterogeneously. The basal or outermost layer of ductal structures and solid
      nests was reactive with antibodies to CK1/5/10/11, CK5/6, and CK14. With regard
      to CK expression, the results indicate that syringoma represents a tumor
      differentiating toward both the uppermost part of the dermal duct and the lower
      intraepidermal duct (sweat duct ridge) of the eccrine sweat gland.

PMID- 1373585
TI  - Cystic giant solitary trichoepithelioma.
AB  - A case of a giant solitary trichoepithelioma is reported. The tumor was located
      on the thigh, extending from the deep dermis to the subcutaneous tissue with no
      epidermal contact, and showed a large central cystic cavity that measured 9 cm x
      4 cm. We review the cases published under this and other names.

PMID- 1373586
TI  - Reversal of streptokinase-induced bleeding with aprotinin for emergency cardiac
      surgery.
AB  - Two patients requiring emergency cardiac surgery following the administration of
      streptokinase are described. In each case aprotinin was given to counteract the
      haemorrhagic effects of the streptokinase.

PMID- 1373587
TI  - Myelin and myelinization in the telencephalon and mesencephalon of the lizard
      Gallotia galloti as revealed by the immunohistochemical localization of myelin
      basic protein.
AB  - We have studied in the telencephalon and mesencephalon of the lizard Gallotia
      galloti the localization and the chronology of appearance of the immunoreactivity
      due to the presence of a myelin-specific protein: the Myelin Basic Protein (MBP).
      MBP-like immunoreactivity was present with different degrees of intensity in many
      nerve fibers (isolated, in tracts and in commissurae) and it was apparently more
      abundant in mesencephalon. During ontogeny the earliest MBP-like immunoreactivity
      was detected at E.36 in few tracts in mesencephalon and appeared at E.40 in
      telencephalon, proceeding caudo-rostrally and from the ventral (basal) to the
      dorsal (alar) regions. Accumulation of MBP continued after hatching.
      Oligodendrocyte cell bodies were not immunopositive, not even at the youngest
      ages studied.

PMID- 1373588
TI  - [Neoangiogenesis and human amniotic membrane. A clinico-instrumental study in
      phlebostatic ulcer of the lower extremities].
AB  - The present study was made in order to determine if granulation tissue
      development after treatment with Human Amniotic Membrane (HAM) is related with
      instrumental photoplethysmographically evidenced changes of the "ulcus layer".
      Daily, HAM fragments were disposed along the continuity solution of external
      patients with opened postthrombotic ulcus cruris. Instrumental examinations were
      made before, a week after and two weeks after treatment, and after the complete
      ulcus healing. Ulcus with a slight granulous or fibrogranulous layer developed a
      granulation tissue within the first week of treatment. On the contrary, in
      continuity solutions with necrotic layer, treatment with HAM failed. After the
      first week of treatment, a 84% of ulcus with slight granulation and
      fibrinogranulation, presented some sphygmic variations respect to baseline
      levels, like: raising in the amplitude and dicrotism appearing. Within the first
      week, all of the continuity solutions showed significant sphygmograms with a
      regular vascularization on the layer, this period of time concurred with the
      complete granulation phase of the ulcus. Long-preserved HAM stimulates in a
      significant way the appearing of the granulation tissue, within the first week of
      treatment. Sphygmic raisings are directly proportional with the amount of
      granulated tissue evidenced on the layer of the continuity solution.

PMID- 1373589
TI  - Favorable clinical effects of iloprost infusion in 4 uremic patients with
      critical limb ischemia.
AB  - Four uremic patients with advanced peripheral arterial occlusive disease (PAOD)
      of lower limbs causing rest pain and ischemic-necrotic lesions were treated with
      a four-hour intravenous infusion of iloprost at doses of 0.75-2.5 ng/kg/min for
      twenty-eight days. After a week of the therapy all patients experienced
      disappearance of rest pain and prolonged walking distance. At the end of the
      trial a diabetic patient showed a complete regression of the necrotic areas of
      two toes while the other patients still showed ischemic-necrotic foot lesions
      that were well demarcated. Iloprost therapy can be effective in uremic patients
      with severe PAOD.

PMID- 1373590
TI  - NIH conference. Insulin-like growth factors in health and disease.
AB  - The insulin-like growth factor (IGF) family of peptides, binding proteins, and
      receptors are ubiquitous and important for normal human growth and development.
      Modern techniques including specific radioimmunoassays, radioreceptor assays and
      recombinant DNA technology have improved our understanding of the role of IGFs in
      growth and development. In addition to enhancing our understanding of normal
      physiology, these techniques assess changes in these hormones, binding proteins,
      and receptors in pathologic conditions including growth retardation, acromegaly,
      malnutrition, diabetes, and malignancy. Further, these studies have led to
      improvement in the assessment of responses to certain therapies used in the
      treatment of these diseases and may lead to improvements in these therapies.

PMID- 1373591
TI  - An experimental study of prefabricated flaps using silicone sheets, with
      reference to the vascular patternization process.
AB  - A study of the vascularization process in prefabricated flaps, using silicone
      sheets, has been undertaken in rat models. It was found that the survival rate of
      flaps was most stable from 2 to 3 weeks after insertion of the silicone sheet,
      and that this rate decreased when the silicone sheet remained in place beyond
      that period. The results are probably due to the decrease of delayed effect.
      Changes that occurred in the circulation and component blood vessels within the
      flap over time were studied by microangiography, and were categorized at the
      following four stages: at less than 1 week from the initial surgery, from 1 week
      but less than 2 weeks, from 2 weeks but less than 4 weeks, and 4 weeks or more.
      The component vessels consisted of three types, that is, transferred vessels,
      original vessels, and newly formed vessels, with the last type further divided
      into three subtypes, to clarify the timing of the vascular proliferation and
      dilatation for each of the component vessels.

PMID- 1373592
TI  - Modulation of multidrug resistance by immunosuppressive agents: cyclosporin
      analogues, FK506 and mizoribine.
AB  - It has recently been reported that an immunosuppressive agent, cyclosporin A,
      shows a potent overcoming effect on multidrug resistance (MDR). We studied the
      presence of such a modulating effect of cyclosporin analogues and other
      immunosuppressive agents, FK506 and mizoribine, in human multidrug-resistant
      ovarian cancer cells (TAOV/A0.2). The intensity of the overcoming effect of
      cyclosporin analogues against adriamycin resistance was found to be in the other
      of cyclosporin D greater than A greater than C greater than H. It was found that
      cyclosporin D, which has relatively weak immunosuppressive activity, overcame
      adriamycin resistance in the multidrug-resistant ovarian cancer cells to a
      remarkable degree. On the other hand, it was found that FK506, a new potent
      immunosuppressant, could also distinctly modulate adriamycin-resistance. It was
      found that FK506 conferred chemosensitization upon adriamycin with reincreasing
      intracellular adriamycin accumulation in MDR cells which was far less than the
      parent strain. However, in the case of mizoribine, no modulation of drug
      resistance existed. Such modulation was not necessarily accompanied by
      immunosuppressive activity and the two functions were thought to be based on
      different mechanisms.

PMID- 1373593
TI  - Modulation of differentiation-related responses in human colon carcinoma cells by
      protein kinase inhibitor H-7.
AB  - 1-(isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), a potent
      inhibitor of protein kinases, has been used as a tool to examine the role of
      protein kinases in a variety of cellular functions. Contingent on the cell type,
      H-7 has been reported either to inhibit or to promote differentiation. The
      biological effects of H-7 on human colon adenocarcinoma cells have not been
      reported. In this study we investigated the effects of H-7 on differentiation -
      related parameters such as cellular morphology, proliferation, the expression of
      carcinoembryonic antigen (CEA), fibronectin and cytokeratins in human
      adenocarcinoma cell lines HCT116 and SW480. H-7 induced pronounced morphological
      alterations in both cell lines. It induced fibronectin expression and down
      modulated CEA expression and secretion in the SW480 cells, but not in the HCT116
      cells. Expression of acidic keratins was not affected by H-7 treatment in both
      cell lines. However, the expression of basic keratins were down-modulated in the
      HCT116 cells and enhanced in the SW480 cells. These studies showed that the
      protein kinase inhibitor, H-7, modulated phenotypic properties in human colon
      adenocarcinoma cells. Alterations in phenotypic properties and their significance
      in regard to the induction of differentiation are discussed.

PMID- 1373594
TI  - Mapping of antigenic sites to monoclonal antibodies on the primary structure of
      the F1-ATPase beta subunit from Escherichia coli: concealed amino-terminal region
      of the subunit in the F1.
AB  - To analyze relationships between the ternary and primary structures of the beta
      subunit of Escherichia coli F1 ATPase, we prepared two monoclonal antibodies beta
      12 and beta 31 against the beta peptide. These antibodies bind to the beta
      subunit but do not bind to the F1 ATPase, resulting in no inhibition of the
      ATPase activities. Several different portions of the beta subunit peptide were
      prepared by constructing expression plasmids carrying the corresponding DNA
      segment of the beta subunit gene amplified by the polymerase chain reaction.
      Western blotting analysis using these peptides revealed that the antibodies bound
      to a peptide of 104 amino acid residues from the amino terminal end, which is
      outside the previously estimated catalytic domain between residues 140 and 350.
      These results indicated that the amino terminal portion of the maximal 104
      residues is not exposed to the surface of the F1 ATPase. The binding spectrum of
      the antibodies to the subunit from various species including Vibrio alginolyticus
      and thermophilic bacterium PS3 indicated possible epitope sequences within the
      104 residues. The ternary structure of the beta subunit, in terms of cleavage
      sites by endopeptidases, was analyzed using the antibodies. A 43-kDa peptide
      without binding ability to beta 12 and beta 31 appeared upon cleavage by lysyl
      endopeptidase. The results suggested that lysyl residues from around 70 to 100
      from the amino terminus are exposed to the surface of the beta subunit.

PMID- 1373595
TI  - In vitro metabolism of FK-506 in rat, rabbit, and human liver microsomes:
      identification of a major metabolite and of cytochrome P450 3A as the major
      enzymes responsible for its metabolism.
AB  - The metabolism of the immunosuppressant FK-506 was shown to be catalyzed
      primarily by cytochrome P450 isozymes of the P450 3A subfamily. Antibodies
      against rat P450 3A inhibited FK-506 metabolism by 82% in rat liver microsomes
      and by 35-56% in liver microsomes from humans, dexamethasone-induced rats, and
      erythromycin-induced rabbits. Poor species cross-reactivity of the antibodies,
      metabolic switching, and/or some metabolism by P450 isozymes other than P450 3A
      may be responsible for the incomplete inhibition observed. Besides anti-rat P450
      3A, antibodies against rat P450 1A also appeared to have some inhibitory effect
      implicating these particular cytochrome P450 isozymes as having a minor role in
      FK-506 metabolism. The formation of 13-desmethyl FK-506, identified here as a
      major metabolite of FK-506 in all types of microsomes examined, was inhibited
      completely by anti-P450 3A in liver microsomes from dexamethasone-induced rats
      and erythromycin-induced rabbits but only partially in human and control rat
      liver microsomes.

PMID- 1373596
TI  - [THe clinical aspects of benign prostatic hypertrophy: the times are changing].
AB  - To determine if the incidence of benign prostatic hypertrophy (BPH) had increased
      in the general population and to reevaluate the therapeutic approaches, we
      reviewed and compared the clinical records, surgical procedures and therapeutic
      results achieved in 198 patients that had undergone surgery in 1980 (52 patients)
      and 1990 (146 patients). We observed that the number of BPH procedures had
      increased in 1990. These, however, had been performed earlier in the course of
      the disease, in younger patients with more severe, but better controlled
      pathologies.

PMID- 1373597
TI  - [Aspiration cytology in the differential diagnosis of granulomatous prostatitis
      prostatic carcinoma: apropos an illustrative case].

PMID- 1373598
TI  - Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect.
      A review and replication analysis of pandysmaturation in the Jerusalem Infant
      Development Study.
AB  - A 1975 report stated that a schizophrenic genotype may be manifested in infants
      by a neurointegrative defect called pandysmaturation. Recent evidence supports
      this: (1) 12 studies found delayed development in schizophrenics' infants and in
      preschizophrenics; (2) "blind" psychometric evaluations favored an adult
      schizotypal disorder in four to six of seven high-risk subjects with
      pandysmaturation in the New York study; and (3) finally, in a partial replication
      of this method using the Jerusalem data, blind diagnoses of "probable" and
      "possible" pandysmaturation were significantly related to a parental diagnosis of
      schizophrenia and to cognitive and motor neurointegrative deficits at 10 years.
      Obstetrical complications were unrelated to diagnosis, pandysmaturation, or
      outcome in the overall sample. However, we found a small subgroup of
      schizophrenic offspring in whom the most severe motor deficits at follow-up were
      related to obstetrical complications, pandysmaturation, and low birth weight.

PMID- 1373599
TI  - [The potencies of substance P, substance P fragments, and compound 48/80 for
      granulocyte infiltration in mouse skin].
AB  - To determine whether the N-terminal or C-terminal peptide of substance P (SP)
      induces granulocyte infiltration in mouse skin, we examined the potencies of SP,
      the N-terminal peptides SP1-4 and SP1-9, the C-terminal peptides SP4-11 and SP6
      11, and a mast cell degranulating agent compound 48/80 in inducing granulocyte
      (neutrophil and eosinophil) infiltration in the skin of BALB/c mice. The
      subcutaneous administration of SP (10(-7)-10(-5) M) caused granulocyte
      infiltration in mouse skin in a concentration-dependent fashion 6 h after the
      injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration in the
      skin which was associated with mast cell degranulation. However, SP1-4, SP4-11
      and SP6-11 (up to 10(-4) M) induced neither granulocyte infiltration nor mast
      cell degranulation. In addition, compound 48/80 (0.5-50 micrograms/ml) also
      induced granulocyte infiltration of mouse skin with a concentration-dependent
      increase in mast cell degranulation. These results indicate that SP induces
      granulocyte infiltration of mouse skin through mast cell degranulation induced by
      the N-terminal peptide.

PMID- 1373600
TI  - Antigenic heterogeneity in Mycoplasma iowae demonstrated with monoclonal
      antibodies.
AB  - Western blots of proteins of 14 Mycoplasma iowae strains and isolates resolved by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis were probed with three
      monoclonal antibodies (MAbs), MI6, MI7, and MI8. MAb MI6 reacted with one or more
      antigens with apparent molecular weights of 60,000, 70,000, and 94,000. In three
      strains (N-PHN-D13, R-D2497, and K 1805), antigens located on a single peptide
      band were recognized, while in others additional epitopes at different molecular
      weight positions were revealed. A similar pattern was observed with MAb MI7,
      although it reacted with fewer antigens than did MAb MI6 and failed to recognize
      antigens in strains N-PHN-D13 and R-D2497. MAb MI8 reacted with an antigen at an
      apparent molecular-weight position of 28,000 in four of the 14 strains and
      isolates. The diverse reaction patterns observed with the MAbs in the 14 M. iowae
      strains and isolates confirms the occurrence of antigenic variation within this
      species. Antigenic variation in M. iowae may be pivotal in determining host
      parasite interactions, pathogenesis, and the outcome of disease.

PMID- 1373601
TI  - A coagglutination assay with monoclonal antibodies for rapid laboratory
      identification of Mycoplasma synoviae.
AB  - An agglutinating monoclonal antibody (MAb S2) specific for a 55,000-molecular
      weight surface protein of Mycoplasma synoviae was developed by fusion of spleen
      cells from immunized BALB/c mice with P3X63 Ag8.653 myeloma cells. Immunogold
      labeling experiments confirmed the cell surface location of the MAb-recognized
      antigen. MAb S2-coated Staphylococcus aureus was used in a rapid slide
      coagglutination assay. Eleven M. synoviae strains, including the type strain WVU
      1853, coagglutinated with MAb-coated S. aureus, but five M. gallisepticum strains
      (PG31, S6, R, F, and A5969) did not.

PMID- 1373602
TI  - The NADPH-oxidase-associated H+ channel is opened by arachidonate.
AB  - The H+ channel associated with the generation of O2.- by NADPH oxidase and the
      oxidase itself must both be activated in response to stimuli (e.g. phorbol
      esters, chemotactic peptides, certain fatty acids). We have investigated the
      effects of membrane potential, an imposed pH gradient and a combination of the
      two (the protonmotive force) on the H+ conductivity of the cytoplast membrane. H+
      conductivity was observed only in the presence of arachidonate and not in its
      absence. In the presence of arachidonate, H+ movement was determined by the
      protonmotive force. The effect of arachidonate was probably on a channel, since
      this fatty acid did not significantly increase the H+ permeability of artificial
      phospholipid membranes. It appears, therefore, that arachidonate is required both
      for the activation of O2.- production and the associated H(+)-channel-mediated
      efflux.

PMID- 1373603
TI  - Polypeptide N-acetylgalactosaminyltransferase activity in tracheal epithelial
      microsomes.
AB  - Pig tracheal epithelium, a site of extensive mucin biosynthesis, contained
      polypeptide N-acetylgalactosaminyltransferase activity directed towards L
      threonine residues. The enzyme preparation was broadly similar in properties to
      preparations from other tissues, e.g. pig and bovine submaxillary glands, bovine
      colostrum, BW5147 mouse lymphoma and baby-hamster kidney cells. Enzyme was
      membrane-bound and was released from microsomal preparations by extraction with
      Triton X-100. Extracted enzyme had a pH optimum of 7.5, had a requirement for
      Mn2+ (10 mM) and was inhibited by Na2EDTA. The Km for UDP-N-acetylgalactosamine
      was 110 microM and that for an octapeptide acceptor (VTPRTPPP) was 3.0 mM at 37
      degrees C. Using a range of synthetic peptides of known structure related to TPPP
      it was established that L-threonine residues were specifically O-glycosylated
      probably in the alpha-configuration. Synthetic peptides containing the TPPP
      sequence required a peptide length of five or more for significant acceptor
      activity. In VTPRTPPP the two threonine residues were similarly glycosylated, as
      revealed by tryptic cleavage of the glycosylated product and separation of the 3H
      labelled fragments. The enzyme preparation also specifically catalysed the
      transfer of N-acetylgalactosaminyl residues from UDP-N-acetyl[1-3H]galactosamine
      to bovine submaxillary mucin core protein and to myelin basic protein.

PMID- 1373604
TI  - Ca(2+)-dependent changes in the mitochondrial energetics in single dissociated
      mouse sensory neurons.
AB  - Depolarization of neurons promotes Ca2+ influx through voltage-activated
      channels, raising the intracellular Ca2+ concentration ([Ca2+]i). The
      consequences of such changes in [Ca2+]i for mitochondrial function were assessed
      in single, freshly dissociated mammalian neurons. Microfluorimetric techniques
      were used to measure [Ca2+]i, mitochondrial membrane potential [delta psi m,
      Rhodamine 123 (Rh 123) fluorescence], NAD(P)H/NAD(P)+ autofluorescence and
      flavoprotein autofluorescence combined with whole-cell voltage-clamp techniques.
      Brief (100-500 ms) depolarization of the cell membrane by high K+ or by voltage
      commands raised [Ca2+]i and depolarized delta psi m. The change in delta psi m
      was dependent on extracellular Ca2+. Under voltage-clamp control of the cell
      membrane, the voltage-dependence of the change in Rh 123 fluorescence reflected
      that of the Ca2+ current. The response was reduced by Ca2+ buffers introduced
      into the cell. The behaviour of this signal is thus consistent with a
      mitochondrial response to raised [Ca2+]i and does not reflect the change in cell
      membrane potential per se. Similar stimuli caused a rapid decrease of NAD(P)H
      autofluorescence, followed by an increase which could last several minutes.
      Flavoprotein fluorescence increased transiently, followed by a decrease lasting
      for several minutes. These signals indicate an initial oxidation of NAD(P)H and
      FADH, followed by a prolonged increase in the reduced state of both coenzymes.
      All these changes were dependent on extracellular [Ca2+]. Raising [Ca2+]i again
      during the period of NAD+ reduction caused an oxidizing response. Ruthenium Red
      applied to the cells (i) reduced both the Ca2+ current and the depolarization
      induced [Ca2+]i transient and (ii) directly quenched Rh 123 fluorescence. When
      introduced into the cells with patch pipettes, it prevented the changes in
      autofluorescence without interfering with the Ca2+ conductance. Oligomycin
      blocked neither the response of delta psi m nor of NADH autofluorescence,
      suggesting that the signals do not reflect a response to falling ATP/ADP.Pi
      ratios as a consequence of the high [Ca2+]i. The changes in NADH autofluorescence
      were sustained in the presence of iodoacetic acid with pyruvate as substrate.
      Thus brief physiological elevations of [Ca2+]i depolarize delta psi m, probably
      through Ca2+ cycling across the mitochondrial inner membrane. The changes in
      autofluorescence are consistent with (i) increased respiration which could result
      from the depolarization of delta psi m, followed rapidly by (ii) increased
      activity of the Ca(2+)-dependent intramitochondrial enzymes. Changes in [Ca2+]i
      within a physiological range may thus promote significant and long-lasting
      changes in mitochondrial energy production.

PMID- 1373605
TI  - Identification of the insulin-like growth factor binding proteins 5 and 6 (IGFBP
      5 and 6) in human breast cancer cells.
AB  - Four estrogen receptor-positive (ER+) [MCF-7, T47D, ZR75 and BT474] and 3 ER-
      [Hs578T, MDA-MB-468 and MDA-MB-231] human breast cancer cell lines were examined
      for expression of the IGFBP-5 and IGFBP-6 genes. Northern blot analysis revealed
      that all cell lines, except MDA-MB-231, expressed IGFBP-5 mRNA. IGFBP-6 mRNA,
      however, was expressed only by the ER- cell lines. Western immunoblotting
      indicated that the previously unidentified 31-kDa and 32-kDa IGF binding species
      secreted by these cell lines are IGFBP-5. The levels of IGFBP-4 and IGFBP-5 were
      increased in MCF-7 cells by estradiol and IGF-I, respectively, indicating that
      these BPs may contribute to the growth stimulatory response to these mitogens.

PMID- 1373606
TI  - GMP-140 (P-selectin) inhibits human neutrophil activation by lipopolysaccharide:
      analysis by proton magnetic resonance spectroscopy.
AB  - Proton magnetic resonance spectroscopy has been used to monitor the effect of GMP
      140 on the stimulation of human peripheral blood neutrophils. Stimulation of
      neutrophils by lipopolysaccharide gives rise to a high resolution lipid spectrum
      from the intact cells. Fluid phase GMP-140, which prevents adhesion and
      development of inflammatory responses of neutrophils, was found to inhibit these
      changes in the lipid spectrum by up to 40%. Anti-GMP-140 Fab fragments reversed
      this effect while non-immune Fab fragments did not affect the observed inhibition
      by GMP-140.

PMID- 1373607
TI  - Stem cell factor has histamine releasing activity in rat connective tissue-type
      mast cells.
AB  - Stem cell factor (SCF) was documented to be involved in the growth of mast cells
      controlled by fibroblasts. We tested the effect of recombinant rat SCF on
      degranulation from rat peritoneal mast cells (connective tissue-type mast cells:
      CTMC). SCF induced histamine release (approximately 20% of total histamine
      content) in a dose-dependent fashion. The release response was relatively rapid
      and reached a maximum within 5 min. The release showed total dependence on the
      presence of extracellular phosphatidylserine (PTS). These results reveal that SCF
      has histamine releasing activity in CTMC.

PMID- 1373608
TI  - Structure-activity analyses of HIV-1 reverse transcriptase.
AB  - HIV-1 reverse transcriptase is a dimeric enzyme which can exist in both
      homodimeric (p66/p66) and heterodimeric (p66/p51) forms. The monomeric subunits
      are catalytically inert. However, during DNA synthesis by the dimeric enzyme,
      only one subunit (p66) appears to carry out the catalysis, while the second
      subunit serves only a supportive role. In the case of the p66/p66 homodimers, we
      find that both the subunits are catalytically competent as judged by the
      observation that a) primer binding occurs to both subunits and b) catalytically
      inert dimers can be partially activated by replacement of one of the two inactive
      p66 subunits.

PMID- 1373609
TI  - Lipopolysaccharide and serum cause the translocation of G-protein to the membrane
      and prime neutrophils via CD14.
AB  - Lipopolysaccharide (LPS) in combination with human serum, in the absence of a
      second stimulus, causes an increase in the amount of the alpha -subunit (Gi alpha
      2) of the guanine nucleotide binding protein Gi2 associated with the membrane.
      The LPS-serum complex also primes human neutrophils for O2- production in
      response to stimulation by the chemotactic factor fMet-Leu-Phe. Added serum
      factor is essential for priming at low concentrations of LPS. In the presence of
      serum, significant potentiation can be observed at LPS concentration as low as
      0.1 ng/ml. The priming is dose and time dependent. Furthermore, the observed
      actions of the LPS-serum complex are not reversible since they cannot be overcome
      by washing. Monoclonal antibody against CD14 inhibits both the direct and priming
      actions of the LPS-serum complex. On the other hand, neither the antibody against
      CD11b nor the antibody against TNF-alpha inhibits the action of this complex.

PMID- 1373610
TI  - Inhibitors of glycoprotein processing act at an early stage of myogenesis.
AB  - The glycoprotein processing inhibitors bromoconduritol and N-methyl-1
      deoxynojirimycin inhibit myoblast fusion and differentiation, suggesting the
      critical involvement of one or more glycoproteins in the control of skeletal
      myogenesis. In the present study we have examined the effect of inhibitors of
      glycoprotein processing on the expression of the muscle-specific regulatory
      factor myogenin. Glucosidase inhibitors, but not the mannosidase inhibitor 1
      deoxymannojirimycin, inhibited the accumulation of myogenin mRNA in myoblasts,
      and immunoblotting confirmed that this was reflected in reduced accumulation of
      myogenin protein. The results indicate that the glycoprotein(s) critically
      involved in the control of myoblast differentiation act at an early stage in this
      process by modulating expression of the myogenic regulatory factor myogenin.

PMID- 1373611
TI  - Protein kinase C mRNA levels and activity in reconstituted normal human
      epidermis: relationships to cell differentiation.
AB  - Although keratinocytes are a major target of phorbol ester actions, the activity
      and the expression of the eight cloned protein kinase C (PKC) isoenzymes have not
      been studied in detail in human epidermis. Starting from normal human
      keratinocytes, we reconstituted in culture a multilayered epithelial tissue which
      presents many hystological, biochemical, and molecular features of the authentic
      epidermis and we used it as a model to investigate the PKC activity and mRNA
      levels. We found that i) PKC activity is higher in differentiated than in non
      differentiated cells; ii) the mRNA levels of PKC delta and -eta/L, while are
      differently affected by spontaneous keratinocyte differentiation, are down
      regulated during phorbol esters-induced cell differentiation. Our findings could
      represent a basis to investigate the involvement of PKC isoforms in the
      keratinocyte differentiation process.

PMID- 1373612
TI  - Role of CFTR in lysosome acidification.
AB  - The role of CFTR in lysosome acidification was examined in CFPAC-1 pancreatic
      adenocarcinoma cells with the delta F508 mutation that were transduced with a
      retroviral vector (PLJ-CFPAC) or with the normal CFTR gene (CFTR-CFPAC). Steady
      state lysosomal pHi in intact cells was lower in PLJ-CFPAC cells than CFTR-CFPAC
      cells (3.55 vs 3.80) and was not affected by cAMP or forskolin. Initial rates of
      ATP-dependent acidification of isolated lysosomes and steady-state ATP-dependent
      pHi were similar in both cell lines over a range of chloride concentrations and
      were not altered when cells were exposed to cAMP or to forskolin prior to
      preparation of lysosomes. These observations suggest that CFTR plays no role in
      acidification of lysosomes, possibly due to limited permeability of lysosomal
      membranes to chloride.

PMID- 1373613
TI  - Differential regulation of thyrotropin-releasing hormone receptor mRNA levels by
      thyroid hormone in vivo and in vitro (GH3 cells).
AB  - We studied the effect of thyroid status on thyrotropin-releasing hormone receptor
      (TRH-R) mRNA levels both in vivo and in vitro (GH3 cells) using a cloned rat TRH
      R cDNA by RT-PCR. Experimental hypothyroid rats were produced by total
      thyroidectomy and were then killed 7 days after the operation. TRH receptor
      binding in the anterior pituitary and serum TSH level were elevated approximately
      2-fold and 8-fold, respectively, in 7 day thyroidectomized rats. TRH-R mRNA
      levels in hypothyroid rats were also increased significantly compared with those
      of normal rats. In GH3 cells, however, no significant change of TRH-R mRNA level
      was observed between cultures treated with triiodothyronine (T3, 10(-9) and 10(
      7) M) and the untreated group. The present data indicate that 1) the in vivo
      effects of thyroid status on TRH-R mRNA levels differ from the in vitro one, and
      that 2) the down regulation of TRH-R binding by thyroid hormone in GH3 cells may
      be mediated by translational or post-translational mechanisms.

PMID- 1373614
TI  - Evidence for a fourth rat isoform of the plasma membrane calcium pump in the
      kidney.
AB  - This study was conducted to identify plasma membrane Ca(2+)-transporting ATPases
      present in rat kidney. Characterization of the cDNAs of the plasma membrane
      Ca(2+)-ATPases revealed a family of proteins with regions of highly conserved
      amino acid sequence. To examine the extent of the diversity of rat renal plasma
      membrane Ca(2+)-ATPases, we used the polymerase chain reaction to detect
      additional gene products in rat kidney mRNA that shared these conserved regions.
      Sequences corresponding to three previously known rat plasma membrane Ca(2+)
      ATPases were obtained. In addition, we found sequence corresponding to a new
      putative plasma membrane Ca(2+)-ATPase. Our results demonstrate that the rat
      kidney contains at least four different plasma membrane Ca(2+)-ATPases and the
      complexity of this multigene family is greater than previously thought.

PMID- 1373615
TI  - Further analysis of a transcript nested within the actin 5C gene of Drosophila
      melanogaster.
AB  - Previously we uncovered a 0.45-kb transcript within the 3' end transcribed
      untranslated region (3'UTR) of actin gene at 5C3-4 (act5C) of Drosophila
      melanogaster. We report here that its sequence bears no similarity to the known
      DNA or protein sequences. This and act5C transcripts are loaded on different
      polyribosomal classes. Gel retardation experiments performed with this fragment
      and several others from act5C reveal no DNA binding activity. The 0.45-kb
      transcript, initially isolated from different developmental stages of D.
      melanogaster embryogenesis, is also expressed in Drosophila Kc tissue culture
      cells, which will be used in transformation experiments designed to identify
      regulatory features of the nested gene and its possible interaction at some level
      with its "host" act5C gene.

PMID- 1373616
TI  - Inhibition by mepacrine and amylase secretion from intact and permeabilized rat
      pancreatic acini.
AB  - In intact rat pancreatic acini, the phospholipase A2 inhibitor mepacrine did not
      affect basal amylase release but dose-dependently inhibited the carbachol (IC50
      65 microM) and CCK-8 (IC50 210 microM)-stimulated amylase release. In
      permeabilized acini, mepacrine shifted the dose-response curve for calcium to the
      right by a factor 2 and inhibited the release of amylase stimulated by GTPrS.
      From these results we conclude that carbachol, CCK-8 and GTPrS probably activate
      a phospholipase A2 closely coupled to exocytosis.

PMID- 1373617
TI  - Pleiotrophin gene expression is highly restricted and is regulated by platelet
      derived growth factor.
AB  - Pleiotrophin (PTN) is a growth and neurite extension promoting polypeptide which
      is highly expressed in brain and in tissues derived from mesenchyme. The PTN gene
      is developmentally regulated and is closely related to the MK and RI-HB genes,
      both of which are developmentally regulated and induced by retinoic acid. We now
      have screened 17 cell lines and report that expression of the PTN gene in these
      cells is restricted to embryo fibroblasts and intestinal smooth muscle cells.
      However, NIH 3T3 cells stimulated by the platelet-derived growth factor (PDGF)
      express a marked increase in levels of PTN mRNA whereas retinoic acid failed to
      increase levels of PTN mRNA in NIH 3T3 cells or in F9 embryonal carcinoma cells
      within 72 hours of exposure. The results suggest that expression of the PTN gene
      is highly restricted and that the PTN gene is a new member of the PDGF-induced
      cytokine family.

PMID- 1373618
TI  - Neurotrophic factor-like activity in Drosophila.
AB  - The NGF-family of neurotrophic factors are structurally similar peptides with
      related functional properties. So far, this family of neurotrophic factors has
      only been identified in the vertebrate nervous system. We have determined that
      cultured Drosophila embryonic cells produce and secrete into medium, an activity
      which stimulates neurite outgrowth of embryonic chick sensory ganglia. This
      Drosophila activity can be blocked by antibodies to mouse NGF, indicating an
      immunological relationship between the Drosophila factor, mouse NGF and possibly
      other vertebrate neurotrophic factors. Addition of mouse NGF to Drosophila
      embryonic cells in culture results in increased cell number and enrichment of the
      neuronal phenotype, indicating that Drosophila cells have the ability to respond
      to the vertebrate factor. In addition, poly(A)+RNA extracted from Drosophila
      contains a single 1.4 Kb band which cross-hybridizes with a mouse NGF cRNA probe.
      These results indicate that vertebrate neurotrophic factor-like functions may
      operate in a genetically defined invertebrate species.

PMID- 1373619
TI  - Neuropeptides and inflammation. A somatostatin analog as a selective antagonist
      of neutrophil activation by substance P.
AB  - OBJECTIVE: Substance P and somatostatin are neuropeptides found in peripheral
      sensory nerves. In vitro, these have opposing effects on inflammatory cells. We
      compared the effects of these peptides on the activation of neutrophils. METHODS:
      Neutrophils were isolated from healthy volunteers, and chemotaxis, superoxide
      anion generation, aggregation, and changes in cytosolic calcium and GTPase
      activity were measured in the presence of substance P, somatostatin, and the
      chemoattractant FMLP. RESULTS: Substance P was an effective chemoattractant, 20%
      as potent as FMLP at equimolar concentrations. Substance P also stimulated GTPase
      activity in neutrophil plasma membranes. Somatostatin did not activate
      neutrophils; however, it effectively inhibited neutrophil chemotaxis and GTPase
      activity provoked by substance P, but not by FMLP. CONCLUSIONS: These studies
      demonstrate that substance P can effectively stimulate chemotaxis, possibly via
      effects on a GTP-binding protein distinct from that triggered by FMLP, and that
      somatostatin is a selective antagonist of substance P. The biochemical
      specificities of these peptides on cells may modulate neurogenic inflammation at
      the local level.

PMID- 1373620
TI  - Synovial fluid analysis of two groups of proteoglycan epitopes distinguishes
      early and late cartilage lesions.
AB  - OBJECTIVE: To investigate whether fragmentation of proteoglycans in arthritis
      results in domains that have different levels of release from cartilage at
      different stages of the disease. METHODS: Two regions of the proteoglycan, the
      hyaluronan-binding region and the glycosaminoglycan-rich region of the core
      protein, were measured, by immunoassay, in knee joint synovial fluids of patients
      with rheumatoid arthritis or reactive arthritis. RESULTS: Synovial fluid
      concentrations of the glycosaminoglycan-rich region were highest in rheumatoid
      arthritis patients who had little cartilage damage as determined by radiography,
      whereas release of the hyaluronan-binding region predominated in patients with
      advanced cartilage destruction. In reactive arthritis, release of the
      glycosaminoglycan-rich region predominated. CONCLUSION: These findings indicate
      that the hyaluronan-binding region is initially retained in the tissue during the
      development of cartilage destruction. The combined analysis of these markers
      offers a new avenue for assessment of the degree of cartilage damage in
      arthritis.

PMID- 1373621
TI  - Isolation and culture of synovial microvascular endothelial cells.
      Characterization and assessment of adhesion molecule expression.
AB  - OBJECTIVE: In vitro studies investigating the role of the synovial endothelium in
      the pathogenesis of rheumatoid arthritis (RA) have, until recently, been
      performed using cultured endothelial cells of nonsynovial macrovascular origin.
      In an attempt to more correctly model in vivo conditions, a method for the
      isolation and culture of synovial microvascular endothelial cells (SMEC) has been
      developed. METHODS: SMEC were isolated, primarily, by the use of lectin-coated
      (Ulex europaeus agglutinin type I), magnetizable polystyrene beads. RESULTS:
      Isolated cells exhibit classic endothelial "cobblestone" morphology, express von
      Willebrand factor, metabolize acetylated low-density lipoprotein, and exhibit a
      cytokine (interleukin-1)-mediated expression of endothelial leukocyte adhesion
      molecule type 1 (ELAM-1) and intercellular adhesion molecule type 1 (ICAM-1).
      ELAM-1 levels were significantly elevated in SMEC, compared with human umbilical
      vein endothelial cells, over a range of interleukin-1 concentrations. CONCLUSION:
      This increased expression of ELAM-1 by SMEC may be a potentiating step in the
      pathogenesis of RA.

PMID- 1373622
TI  - Interferon-alpha in lupus psychosis.
AB  - OBJECTIVE: Since the level of interferon-alpha (IFN alpha) is increased in the
      sera of patients with active systemic lupus erythematosus (SLE) and is detectable
      in the cerebrospinal fluid (CSF) of some SLE patients with neuropsychiatric
      manifestations, we investigated the contribution of IFN alpha to the pathogenesis
      of the neuropsychiatric manifestations of SLE. METHODS: IFN alpha levels were
      quantitated by radio-immunoassay in CSF and serum samples from 17 SLE patients
      with neuropsychiatric manifestations and 28 patients with SLE alone or SLE and
      other neurologic disorders. RESULTS: Levels of IFN alpha were increased in the
      CSF of 5 of 6 patients with lupus psychosis, and in 4 of these 5 patients, the
      levels in CSF were higher than those in serum. IFN alpha levels decreased when
      the manifestation of lupus psychosis subsided. In contrast, IFN alpha levels in
      CSF samples from patients with seizures alone were not increased. One patient
      with lupus psychosis died of complications of generalized seizures resulting from
      the SLE. At autopsy, we investigated whether IFN alpha protein or messenger RNA
      was detectable in the subject's brain. IFN alpha protein was
      immunohistochemically demonstrated in the neurons and in the microglia (focal
      accumulation), features not present in the brain tissues of subjects who died of
      other diseases. CONCLUSION: These findings support the hypothesis that IFN alpha,
      possibly synthesized in the brain, is the cause of the manifestation of psychosis
      in patients with SLE.

PMID- 1373623
TI  - Breast self examination: use of a visual reminder to increase practice.
AB  - 1. Breast cancer, the most common type of cancer affecting women and the second
      leading cause of cancer death in women, will affect more than 10% of the female
      population of this country. 2. Breast self examination (BSE), known to be an
      effective component of a three part breast health program which includes physical
      examination and mammography, is not practiced consistently by American women. 3.
      A convenient memory aid serving as a visual stimulus, combined with appropriate
      educational materials, is effective in increasing both the knowledge of breast
      health and the frequency of BSE practice.

PMID- 1373624
TI  - The effect of low molecular weight dextran on haemodynamics and respiratory
      function during endotoxin-induced shock.
AB  - The effects of low molecular weight dextran (LMWD) infusion, on gas exchange and
      haemodynamics were evaluated in sheep during endotoxin shock. The infusion of
      LMWD was started after signs of shock and lung injury were evident. After a
      stabilization period 10 micrograms kg-1 E. Coli endotoxin was infused i.v..
      Endotoxin infusion resulted in an marked increase in pulmonary artery pressure
      (PAP) and decrease in mean arterial pressure (MAP), respiratory compliance,
      arterial oxygen tension (PaO2) and oxygen delivery index (DO2l). After 3 h MAP,
      PaO2, DO2l and compliance improved significantly in LMWD treated animals. The PAP
      had also decreased significantly in the LMWD-treated animals, but remained high
      in the controls (P less than 0.01). It was concluded that LMWD infusion improves
      haemodynamics and gas-exchange in sheep during endotoxin shock.

PMID- 1373625
TI  - Molecular structure and granulocyte/macrophage colony-stimulating factor
      activity.
AB  - Granulocyte/macrophage colony-stimulating factor (GM-CSF) plays a critical role
      in myeloid differentiation and in several immune and inflammatory processes. GM
      CSF binds to specific cellular receptors (GM-CSFR) which belong to a recently
      described supergene family. These receptors are potential targets for
      pharmacologic design and such design depends on a molecular understanding of
      ligand-receptor interactions. We present our initial studies evaluating the
      potential active sites of the molecule. The sites on the GM-CSF molecule that
      were studied represent two alpha-helices predicted to be critical for GM-CSF
      activity, as implicated by human-murine chimeric molecule studies. These helices
      are predicted to be adjacent in native GM-CSF. Peptides corresponding to amino
      acids 17-31 and 78-99 of GM-CSF were synthesized and cross-linked to one another
      in two different orientations. The ability of anti-GM-CSF to bind the individual
      and complexed peptides was evaluated by both ELISA and radioimmunoassay.
      Significant binding to all peptides was demonstrated. A preferred orientation of
      the two peptides was apparent, and this agreed with the predicted model
      structures. Antibodies were developed against the coupled peptides, and these
      demonstrated significant cross-reactivity with recombinant human GM-CSF.
      Additionally, analyses of anti-peptide antisera binding studies predict these two
      amino acid sequences to lie in parallel planes to one another in the native human
      GM-CSF molecule.

PMID- 1373626
TI  - Structural aspects of recognition motifs contributing to autoimmune responses.
AB  - Sequence analysis of autoimmune-associated antibodies has suggested a structural
      relatedness between genes used to encode autoantibodies and those encoding
      unrelated antibodies without autoreactive specificities. Subsequently, the basis
      for cross-reactive idiotypes across germ-line lineages, as well as conserved
      interspecies cross-reactivities of autoantigens among serologically similar
      antibodies, may result from evolutionary duplication of particular types of
      recognition motifs. As a first step toward elucidating structural recognition
      principles underlying possible cross-reactive epitopes involved in autoimmune
      pathologies, structural features of selected motifs associated with native ligand
      binding are examined for their inherent occurrence in antibody and T-cell
      receptor repertoires. This analysis considers the putative recognition features
      representative of common motif subsets shared with loop structures in CDR2 and
      FR3 regions of antibodies such as charge-2x-charge-x-charge or hydrogen bond
      donor (acceptor)-2x-charge-x-hydrogen bond donor (acceptor) type motifs, where x
      is any residue that can participate in maintaining a loop conformation. Such
      tracts encoded in the CRD2 and FR3 regions of heavy chains of antibodies and T
      cell receptors (TCRs) associated with autoimmune dysfunction, with non
      autoreactive antibodies, and with native host proteins. Such evolutionarily
      conserved motifs may be targets for complementary interactions involving
      autoantibodies and receptors.

PMID- 1373628
TI  - Infection of HIV-1 and HIV-2 through the luminal and serosal sides of polarized
      human intestinal epithelial cells.

PMID- 1373627
TI  - Infection of human brain cells by HIV-1: restricted virus production in
      chronically infected human glial cell lines.
AB  - OBJECTIVE: To study expression of HIV-1 in human glial cell lines. DESIGN:
      Chronically HIV-1-infected glial cell lines were established to evade potential
      artefacts resulting from unphysiological viral entry (i.e., transfection). These
      cell lines were used to study viral expression and regulation. METHODS:
      Chronically infected glial cell lines were established by terminal dilution
      cloning of human glioma cells exposed to HIV-1. Virus production and expression
      were assayed by measuring reverse transcriptase activity, p24-antigen levels and
      syncytia-inducing capacity in C8166 target cells (extracellular), or by indirect
      immunoperoxidase staining, immunoblot analysis, and p24- and Nef-antigen-capture
      enzyme-linked immunosorbent assays (intracellular). HIV-long terminal repeat
      (LTR)-dependent expression of the chloramphenicol acetyltransferase reporter gene
      was determined in transient transfection assays. RESULTS: Culture supernatant
      from chronically HIV-1-infected glial cells contained only low levels of virus
      compared with chronically HIV-infected fibroblasts and T-lymphoma cells. Detailed
      study of HIV-antigen expression in representative glial cell line TH4-7-5
      indicated the presence of all major structural proteins, albeit at low levels,
      and of Vif, Tat, Rev and Nef. Intracellular levels of Nef exceeded p24-antigen
      levels by approximately 10-fold. Virus was recovered from TH4-7-5 cells by
      cocultivation with blood-derived target cells, indicating that low-level virus
      production is not due to defective provirus. Prominent negative regulatory
      element (NRE)-mediated suppression of exogenous HIV-LTR activity was observed in
      TH4-7-5 cells and was unequalled by chronically HIV-producing fibroblast cells or
      by uninfected fibroblast and glial cells. CONCLUSIONS: Our results suggest that
      restricted virus production by chronically infected glial cells involves LTR
      mediated regulation of virus expression.

PMID- 1373629
TI  - Phenylethanoid and lignan glycosides from Verbascum thapsus.
AB  - Verbascum thapsus afforded, in addition to three known phenylethanoid glycosides
      and four lignan ones, five new phenylethanoid glycosides and one new lignan
      glycoside. Structures of the compounds were elucidated by spectroscopic methods
      and chemical evidence.

PMID- 1373630
TI  - Nobel lecture. Ion channels for communication between and within cells.

PMID- 1373631
TI  - Nobel Lecture. Elementary steps in synaptic transmission revealed by currents
      through single ion channels.

PMID- 1373632
TI  - The KA-2 subunit of excitatory amino acid receptors shows widespread expression
      in brain and forms ion channels with distantly related subunits.
AB  - A new ionotropic glutamate receptor subunit termed KA-2, cloned from rat brain
      cDNA, exhibits high affinity for [3H]kainate (KD approximately 15 nM). KA-2 mRNA
      is widely expressed in embryonic and adult brain. Homomeric KA-2 expression does
      not generate agonist-sensitive channels, but currents are observed when KA-2 is
      coexpressed with GluR5 or GluR6 subunits. Specifically, coexpression of GluR5(R)
      and KA-2 produces channel activity, whereas homomeric expression of either
      subunit does not. Currents through heteromeric GluR5(Q)/KA-2 channels show more
      rapid desensitization and different current-voltage relations when compared with
      GluR5(Q) currents. GluR6/KA-2 channels are gated by AMPA, which fails to gate
      homomeric GluR6 receptor channels. These results suggest possible in vivo
      partnership relations for high affinity kainate receptors.

PMID- 1373633
TI  - [Clinical biochemical and genetic aspects of peroxisome-deficient disorders].
AB  - Peroxisome-deficient disorders including Zellweger syndrome, neonatal
      adrenoleukodystrophy and infantile Refsum disease are characterized by hypotonia,
      psychomotor delay, hepatomegaly and dysmorphism. Multiple peroxisomal enzymes are
      deficient in these disorders probably due to the defect of transport machinery of
      enzymes. Defects of beta-oxidation enzymes causes an accumulation of very-long
      chain fatty acids, which is closely related to the pathogenesis. Catalase, a
      marker enzyme of peroxisome, is distributed in the cytosol. Immunocytochemical
      staining of peroxisomes using anti-catalase is a useful tool for prenatal and
      postnatal diagnosis. Although the primary etiology of peroxisomal deficiency has
      not been determined, genetic heterogeneity was clarified by complementation
      studies. At least 8 genes are involved in the formation of functional
      peroxisomes.

PMID- 1373634
TI  - Cyclic alternating chemotherapy of high-grade malignant non-Hodgkin lymphomas
      with VIM-Bleo and CHOP.
AB  - Between 1986 and 1988, 81 patients with high grade malignant non-Hodgkin lymphoma
      according to the Kiel classification were treated with the VIM-Bleo/CHOP-regimen:
      etoposide 100 mg/m2 intravenously on days 1-3, ifosfamide 1.5 g/m2 intravenously
      days 1-5 with mesna for prophylaxis of cystitis, methotrexate 30 mg/m2
      intravenously on days 3, bleomycin 10 mg intravenously on days 8 and 15,
      cyclophosphamide 750 mg/m2 day 22, doxorubicin 50 mg/m2 day 22, vincristine 1.4
      mg/m2 on day 22, and prednisolone 100 mg postoperatively on days 1-5 and 22-26.
      Cycles were repeated four times beginning on day 43. Regions with bulky disease
      were irradiated after chemotherapy. 36 patients (44%) had stage II, 12 (15%)
      stage III and 33 (41%) stage IV disease. B-symptoms were present in 49% of
      patients. Serum lactate dehydrogenase activity was elevated in 53%. Overall, 59
      patients (73%) achieved a complete and 14 (17%) a partial remission. 8 (9%) had
      stable or progressive disease. After a median follow up of 30 months thus far,
      probability of long-term relapse free survival is 66% for patients in complete
      remission. Overall survival is 72% at 24 months. Toxicity from treatment was very
      low with leukopenia being the main side effect. Major infections were observed in
      only 2% of cycles with one treatment related death. VIM-Bleo/CHOP is a well
      tolerated regimen with remission rates in the range of other, more toxic
      regimens. However, cyclic alternating treatment did not improve results as
      compared with repeated treatment with a single standard protocol.

PMID- 1373635
TI  - A dose-escalation study of recombinant interferon-alpha in patients with a
      metastatic carcinoid tumour.
AB  - The efficacy of interferon alpha-2b in doses up to 12 x 10(6) IU three times
      weekly was studied in 21 patients with a metastatic carcinoid tumour. Of these 21
      patients, 19 were evaluable for response. Patients were treated with escalating
      dosages of interferon alpha-2b: 3 x 10(6) IU, 6 x 10(6) IU and 12 x 10(6) IU. The
      escalation was performed every 8 weeks when no objective tumour regression was
      observed. Patients were also evaluated for biochemical response and symptomatic
      improvement. One objective tumour regression was observed. Of the 15 patients
      with elevated 5-hydroxyindole acetic acid (5-HIAA) excretion, 5 (33%) had a more
      than 50% decrease in 5-HIAA excretion. Relief of symptoms occurred in 11 patients
      (58%). This improvement was already apparent during the initial 8 weeks of
      treatment. Increasing the dose to 6 or 12 x 10(6) IU interferon alpha-2b did not
      result in further symptomatic improvement. In contrast toxicity was considerable
      with the higher dosages of interferon alpha-2b. It is concluded that low dose
      interferon alpha-2b (3 x 10(6) IU) three times weekly is as effective as higher
      dosages of interferon alpha-2b at ameliorating symptoms of the carcinoid
      syndrome.

PMID- 1373636
TI  - POMB/ACE chemotherapy in non-seminomatous germ cell tumours: outcome and
      importance of dose intensity.
AB  - This study reports the outcome of POMB/ACE (cisplatin, vincristine, methotrexate,
      bleomycin, actinomycin D, cyclophosphamide, etoposide) chemotherapy in 53 male
      patients with metastatic non-seminomatous germ cell tumour (NSGCT) treated
      between 1983 and 1989 in one centre. The overall complete response (CR) rate was
      62% [95% confidence interval (CI) 49-75%), and for patients with large or very
      large volume disease (L/VL, MRC criteria), the CR rate was 56% (95% CI 41-71%).
      The overall 5 year survival was 61%, and for L/VL volume disease 67%. Comparison
      with previous studies suggests that POMB/ACE chemotherapy is not superior to BEP,
      even in patients with adverse prognostic factors. Increased average relative dose
      intensity and increased relative dose intensity of cisplatin over the first seven
      courses were not associated with improved survival. However, in patients
      receiving a relative dose intensity of etoposide greater than or equal to 0.75,
      survival at 5 years was significantly improved compared with those in whom this
      parameter was less than 0.75 (79% vs. 44%, P less than 0.05), suggesting that
      dose intensity of etoposide may be an important determinant of outcome in the
      chemotherapy of metastatic NSGCT.

PMID- 1373637
TI  - [Some markers reflecting the pathology and disease activity of multiple
      sclerosis].

PMID- 1373638
TI  - [Development diagnosis from a therapeutic pedagogical viewpoint].

PMID- 1373639
TI  - [Presence of parents in a neuro-pediatric ward--the parents' viewpoint].

PMID- 1373640
TI  - Colony stimulating factor-1 stimulates Ishikawa cell proliferation and lipocortin
      II synthesis.
AB  - Proliferation of the Ishikawa human endometrial adenocarcinoma cell line is under
      the concerted control of oestrogen and progesterone. Here we demonstrate that
      Ishikawa cells express colony stimulating factor-1 (CSF-1), CSF-1 receptor mRNA
      and are growth stimulated by CSF-1 treatment. An early event associated with CSF
      1 treatment is the induction of lipocortin II synthesis, a protein whose
      expression is also under oestrogen and progesterone control. However, neither CSF
      1 or CSF-1 receptor mRNA appear to be modulated by oestrogen or progesterone.

PMID- 1373641
TI  - Immunocytochemical determination of estrogen and progesterone receptors in human
      endometrial adenocarcinoma cells (Ishikawa cells).
AB  - The regulation of both estrogen and progesterone receptor levels in human
      endometrial adenocarcinoma cells of the Ishikawa line was investigated
      immunocytochemically by using monoclonal antibodies. Positive staining for
      estrogen and progesterone receptors was observed in the nuclei of Ishikawa cells.
      Intercellular heterogeneity in receptor content was evident from the presence of
      receptor-positive or -negative cells and from differences in staining intensity
      of positive cells. Quantitative analysis was performed by scoring the staining
      intensity and the proportion of positively stained cells. The time and dose
      dependent stimulatory effect of estradiol added to culture media on progesterone
      receptor levels was studied by applying both immunocytochemical and biochemical
      methods. Estradiol at 10 nM (optimal concentration) increased the intensity score
      for PR from an initial value of 10.1 to 78.3 after 72 h incubation, and the
      proportion of the positive staining cells from 6.7 to 42.7%. Promegestone (R5020)
      was effective at 1 microM concentration in decreasing the intensity score for ER
      from 31.1 to 14.6 after 72 h exposure and the proportion of positive cells from
      19.0 to 11.4%.

PMID- 1373642
TI  - Requirement of certain epitope specificities of glycosylation inhibiting factor
      for the suppression of in vivo IgE and IgG antibody responses.
AB  - The ovalbumin (OVA)-specific T cell hybridoma 71B1, which constitutively secretes
      glycosylation inhibiting factor (GIF) and is specific for the immunogenic epitope
      represented by amino acids 323-339 in the OVA molecules, failed to form GIF
      having affinity for nominal antigen upon stimulation with OVA-pulsed antigen
      presenting cells (APC). However, the GIF produced by the antigen-stimulated 71B1
      cells bound to the mAb 14-12, which is specific for the antigen-binding chain of
      effector type suppressor T cell factor (TseF), and to mAb specific for TCR. The
      GIF constitutively released from unstimulated 71B1 cells failed to bind to any of
      these antibodies. Gel filtration of GIF preparations showed that the 14-12+ GIF
      from the antigen-stimulated 71B1 cells are composed of 80-100 and 25-35 kDa
      species, while the GIF from unstimulated cells was 12-15 kDa. Reduction and
      alkylation treatment of the GIF from the antigen-stimulated cells resulted in the
      disappearance of the 80-100 and 25-35 kDa GIF, which was accompanied by the
      formation of the 12-15 kDa GIF. Thus, the GIF from the antigen-stimulated 71B1
      cells was similar to the previously described OVA-binding GIF from the 231F1
      cells with respect to their antigenic structures and molecular size, and both
      factors appear to be composed of the 14-12+ polypeptide chain and 12-15 kDa non
      specific GIF. However, the GIF from the antigen-stimulated 71B1 cells lacked
      affinity for the native OVA or synthetic peptide 323-339, and failed to suppress
      the in vivo antibody response to dinitrophenyl (DNP)-OVA. In contrast, the OVA
      binding GIF has affinity for native OVA and the peptide 307-317, to which the
      cell source of the factor is specific, and suppressed the in vivo anti-hapten
      antibody response to DNP-OVA. The results suggest that formation of antigen
      specific TsF is confined to T cells with certain epitope specificities. It was
      also found that the OVA-binding GIF failed to suppress the in vivo anti-hapten
      antibody response to DNP-conjugates of urea-denatured OVA (UD-OVA), which does
      not bind OVA-binding GIF. However, APC pulsed with UD-OVA appear to express the
      epitope 307-317 for which the OVA-binding GIF has affinity. The results
      collectively suggest that the affinity of GIF for an immunizing antigen, rather
      than processed antigen, is required for immunosuppression.

PMID- 1373643
TI  - Role of endogenous peptide in human alloreactive cytotoxic T cell responses.
AB  - The T x B hybrid 174 x CEM.T2 (T2) has been shown to be defective in the
      processing of proteins for presentation by MHC class I molecules. It continues,
      however, to express significant quantities of HLA-A2.1, suggesting that this
      class I molecule is expressed either in a largely peptide-free form or in
      association with a small subset of peptides. In this paper T2 was used in
      conjunction with limiting dilution analysis to provide a direct estimate of the
      fraction of alloreactive cytotoxic T lymphocytes (CTLs) that were dependent upon
      the presence of peptides for their recognition of HLA-A2.1. Alloreactive
      cytotoxic T cell lines generated by stimulation with HLA-A2.1 expressing
      peripheral blood lymphocytes recognized T2 poorly. Split-well analysis of 240
      clonal limiting dilution cultures demonstrated that this reflected the existence
      of two subpopulations. An average 85% of HLA-A2.1 specific CTLs recognized HLA
      A2.1 on normal cells but not on T2. The remainder recognized HLA-A2.1 on both T2
      and normal targets. CTL lines with the latter specificity could be generated by
      using T2 as a stimulator cell. Using target cells that either expressed a lower
      density of HLA-A2.1 or that expressed HLA-A2 molecules that had been mutated to
      affect CD8 binding, no significant differences in avidity between T2-reactive and
      T2-unreactive CTLs were seen. Thus the failure of the majority of alloreactive
      CTLs to recognize T2 is not a consequence of the lower level of HLA-A2.1 surface
      expression on this cell, but is instead due to the absence of appropriate
      epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373644
TI  - IL-4-induced expression of germline gamma 1 transcripts in B cells following
      cognate interactions with T helper cells.
AB  - T cell-dependent B cell activation and the induction of isotype switching require
      antigen and direct contact with helper T (Th) cells. During activation, B cells
      can switch from the expression of IgM to that of IgG, IgE or IgA, depending on
      the lymphokines secreted by the Th cell with which they interact. Studies of
      lipopolysaccharide (LPS)-activated B cells have suggested that lymphokines
      regulate isotype switching via a transcriptional mechanism that increases the
      accessibility of downstream CH genes to a switch recombinase(s). To assess the
      roles of T cell contact and lymphokines in isotype switching, we have examined
      the accessibility model for the regulation of isotype switching to IgG1 in the
      context of cognate interactions between Th cells and normal B cells. We
      demonstrate that Th2 cells that secrete IL-4 can induce expression of germline
      gamma 1 transcripts in B cells. The steady-state level of germline gamma 1
      transcripts induced by Th2 cells is enhanced as compared with the level induced
      by IL-4 alone or Il-4 and LPS also alters the relative usage of the germline
      gamma 1 transcription initiation sites. Enhanced expression of germline gamma 1
      transcripts requires direct contact between T and B cells suggesting a role for T
      cell contact-mediated signals in regulating the accessibility of switch regions.

PMID- 1373645
TI  - Modulation of IL-4 induced germline epsilon RNA synthesis in human B cells by
      tumor necrosis factor-alpha, anti-CD40 monoclonal antibodies or transforming
      growth factor-beta correlates with levels of IgE production.
AB  - To determine the role of germline epsilon transcription in IgE synthesis, the
      effects of cytokines on germline epsilon RNA synthesis in IL-4 dependent epsilon
      switching in B cells was investigated. Induction of germline epsilon
      transcription in highly purified B cells seems to be a specific property of IL-4,
      since none of the other cytokines tested [IL-1 alpha, beta, IL-2, IL-3, IL-5, IL
      6, IL-7, IL-9, IL-10, G-CSF, GM-CSF, M-CSF, IFN-gamma, IFN-alpha, tumor necrosis
      factor (TNF)-alpha, and transforming growth factor (TGF)-beta] were effective.
      TGF-beta, IFN-gamma, and IFN-alpha inhibit IL-4 dependent IgE synthesis, but only
      TGF-beta blocked germline epsilon RNA synthesis in purified B cells, indicating
      that this may be the mechanism by which TGF-beta inhibits IgE synthesis, and that
      IFN-gamma and IFN-alpha act on other stages of the regulatory process resulting
      in IgE production. IL-5, IL-6, and TNF-alpha enhance IL-4 dependent IgE
      synthesis, but only TNF-alpha enhanced IL-4 induced germline epsilon RNA
      synthesis. Finally, anti-CD40 mAbs and the non-IL-4 producing CD4+ T cell clone
      A3, which in the presence of IL-4 induce IgE synthesis by purified B cells, both
      strongly enhanced germline epsilon transcription. These data, together with the
      observation that epsilon switching in cultures initiated with single sIgM+, sIgE-
      B cells in all instances was preceded by germline epsilon RNA synthesis, indicate
      that there is a strong relationship between germline epsilon transcription and
      IgE synthesis.

PMID- 1373646
TI  - Heterogeneous expression of blood group A-determinant in a human gastric cancer
      cell line derived from a blood group A individual.
AB  - The human gastric cancer cell line MKN 45 was derived from the tumour of a blood
      group A individual, and was known to express large quantities of blood group A
      antigen. Using immunofluorescence we found the MKN 45 cells, donated from the
      Japanese Cancer Research Resources Bank, consisted of A-antigen positive cells
      (18%) and A-antigen negative cells (82%). After limiting dilution, wild type and
      mutant cells were cloned with regard to the expression of a cell surface A
      antigen. ELISA was used to detect A-antigen in the cell extract of the wild type
      cells, but none was evident in those of the mutant cells. However, blood group A
      gene-specified transferase activity of the mutant cells was comparable to that of
      the wild type cells.

PMID- 1373647
TI  - Determination of nucleic acid backbone conformation by 1H NMR.
AB  - In DNA or RNA duplexes, the six-bond C3'-O3'-P-O5'-C5'-C4'-C3' backbone linkage
      connecting adjacent residues contains six torsion angles (epsilon, zeta, alpha,
      beta, gamma, delta) but only four protons. This seriously limits the ability to
      define the backbone conformation by NMR using purely 1H-1H distance geometry (DG)
      methods. The problem is further compounded by the inability to assign two of the
      four backbone protons, namely the poorly resolved H5' and H5'' protons, and
      invariably leads to DG structures with poorly defined backbone conformations. We
      have developed and tested a reliable method to constrain the beta, gamma, and
      epsilon (and indirectly alpha and zeta) backbone torsion angles by lower-bound
      NOE distances to unassigned H5'/H5'' resonances combined with either 1H line
      widths or the conservative use of sigma J measurements; the method relies only on
      1H 2-D NMR data, does not involve any structural assumptions, and leads to much
      improved backbone convergence among DG structures. The C4'-C5' torsion angle
      gamma is constrained by lower-bound NOE distances from H2' and from H6/H8 to any
      H5'/H5'', as well as by sigma JH4, coupling measurements in the 3.9-4.4 ppm
      region; delta is constrained by H1'-H4' NOE distances and by H3'-H4' and H3'-H2''
      J couplings in COSY data; epsilon is partially constrained by H3' line width
      and/or further constrained by subtracting the minimum possible sigma JH3'-H from
      the observed sigma JH3' (COSY) to arrive at the maximum possible JH3'-P, which is
      then converted to H3'-P distance bounds. The angle beta is partially constrained
      via H5'-P and H5''-P distance bounds consistent with the maximum H5'-P and H5''-P
      J couplings derived from the observed H5' and H5'' line widths, while alpha and
      zeta are indirectly constrained by lower distance bounds on the observed (n)H1'
      to (n + 1)H5'/H5'' NOEs combined with the prior partial constraints on beta,
      gamma, delta, and epsilon. The combined effects of these additional constraints
      in determining distance geometry structures have been demonstrated using a 12
      base duplex, [d(GCCGTTAACGGC)]2. Coordinate RMSDs per atom between structures
      refined with these constraints from random-embedded DG structures, from ideal A
      DNA, and from B-DNA starting structures were less than 0.4 A for the central 8
      base pairs indicating good convergence. All backbone angles for the central 8
      base pairs are very well constrained with less than 10 degrees variation in any
      of the 48 torsion angles.

PMID- 1373648
TI  - Conformation and dynamics of an Fab'-bound peptide by isotope-edited NMR
      spectroscopy.
AB  - The dynamics and conformation of the peptide antigen MHKDFLEKIGGL bound to the
      Fab' fragment of the monoclonal antipeptide antibody B13A2, raised against a
      peptide from myohemerythrin, have been investigated by isotope-edited NMR
      techniques. The peptides were labeled with 15N (98%) or 13C (99%) at the backbone
      of individual amino acid residues. Well-resolved amide proton and nitrogen
      backbone resonances were obtained and assigned for eight of the 12 residues of
      this bound peptide. Significant resonance line width and chemical shift
      differences were observed. The 15N and 1H line width variations are attributed to
      differential backbone mobilities among the bound peptide residues which are
      consistent with the previously mapped epitope of this peptide antigen. Local
      structural information was obtained from isotope-directed NOE studies. The
      approximate distances associated with the experimental NOEs were estimated on the
      basis of a theoretical NOE analysis involving the relative integrated intensities
      of the NOE and source peaks. In this way, the sequential NH-NH NOEs obtained for
      seven of the Fab'-bound peptide residues were shown to correspond to interproton
      separations of approximately 3 A or less. Such short distances indicate that the
      backbone dihedral angles of these residues are in the alpha rather than the beta
      region of phi,psi conformational space; the peptide most likely adopts a helical
      conformation from F5 to G11 within the antibody combining site. The significance
      of these results with respect to the type and extent of conformational
      information obtainable from studies of high molecular weight systems is
      discussed.

PMID- 1373649
TI  - In vitro selection of RNAs that undergo autolytic cleavage with Pb2+.
AB  - An in vitro selection method has been developed to obtain RNA molecules that
      specifically undergo autolytic cleavage reactions by Pb2+ ion. The method
      utilizes a circular RNA intermediate which is regenerated following the cleavage
      reaction to allow amplification and multiple cycles of selection. Pb2+ is known
      to catalyze a specific cleavage reaction between U17 and G18 of yeast tRNA(Phe).
      Starting from pools of RNA molecules which have a random distribution of
      sequences at nine or ten selected positions in the sequence of yeast tRNA(Phe),
      we have isolated many RNA molecules that undergo rapid and specific self-cleavage
      with Pb2+ at a variety of different sites. Terminal truncation experiments
      suggest that most of these self-cleaving RNA molecules do not fold like tRNA.
      However, two of the variants are cleaved rapidly with Pb2+ at U17 even though
      they lack the highly conserved nucleotides G18 and G19. Both specific mutations
      and terminal truncation experiments suggest that the D and T loops of these two
      variants interact in a manner similar to that of tRNA(Phe) despite the absence of
      the G18U55 and G19C56 tertiary interactions. A model for an alternate tertiary
      interaction involving a U17U55 pair is presented. This model may be relevant to
      the structure of about 100 mitochondrial tRNAs that also lack G18 and G19. The
      selection method presented here can be directly applied to isolate catalytic RNAs
      that undergo cleavage in the presence of other metal ions, modified nucleotides,
      or sequence-specific nucleases.

PMID- 1373650
TI  - Inhibition of T cell signaling by immunophilin-ligand complexes correlates with
      loss of calcineurin phosphatase activity.
AB  - Calcineurin, a Ca2+, calmodulin-dependent protein phosphatase, was recently found
      to bind with high affinity to two different immunosuppressant binding proteins
      (immunophilins) with absolute dependence on the presence of the
      immunosuppressants FK506 or cyclosporin A (CsA) [Liu et al. (1991) Cell 66, 807
      815]. The binding affinities of the immunophilin-drug complexes toward
      calcineurin and the stoichiometry of the resultant multimeric complexes have now
      been determined, and structural elements of FK506, CsA, and calcineurin that are
      critical for mediating their interactions have been identified. Analogues of
      FK506 (FK520, FK523, 15-O-demethyl-FK520) and CsA (MeBm2t1-CsA and MeAla6-CsA)
      whose affinities for their cognate immunophilins do not correlate with their
      immunosuppressive activities have been prepared and evaluated in biochemical and
      cellular assays. We demonstrate a strong correlation between the ability of these
      analogues, when bound to their immunophilins, to inhibit the phosphatase activity
      of calcineurin and their ability to inhibit transcriptional activation by NF-AT,
      a T cell specific transcription factor that regulates IL-2 gene synthesis in
      human T cells. In addition, FKBP-FK506 and CyP-CsA do not inhibit members of the
      PP1, PP2A, and PP2C classes of serine/threonine phosphatases. These data suggest
      that calcineurin is the relevant cellular target of these immunosuppressive
      agents and is involved in Ca(2+)-dependent signal transduction pathways in, among
      others, T cells and mast cells.

PMID- 1373651
TI  - Errors in RNA NOESY distance measurements in chimeric and hybrid duplexes:
      differences in RNA and DNA proton relaxation.
AB  - Nuclear magnetic resonance experiments reveal that the base H8/H6 protons of
      oligoribonucleotides (RNA) have T1 relaxation times that are distinctly longer
      than those of oligodeoxyribonucleotides (DNA). Similarly, the T1 values for the
      RNA H1' protons are approximately twice those of the corresponding DNA H1'
      protons. These relaxation differences persist in single duplexes containing
      covalently linked RNA and DNA segments and cause serious overestimation of
      distances involving RNA protons in typical NOESY spectra collected with a duty
      cycle of 2-3 s. NMR and circular dichroism experiments indicate that the segments
      of RNA maintain their A-form geometry even in the interior of DNA-RNA-DNA
      chimeric duplexes, suggesting that the relaxation times are correlated with the
      type of helix topology. The difference in local proton density is the major cause
      of the longer nonselective T1s of RNA compared to DNA, although small differences
      in internal motion cannot be completely ruled out. Fortunately, any internal
      motion differences that might exist are shown to be too small to affect cross
      relaxation rates, and therefore reliable distance data can be obtained from time
      dependent NOESY data sets provided an adequately long relaxation delay is used.
      In hybrid or chimeric RNA-DNA duplexes, if the longer RNA relaxation times are
      not taken into account in the recycle delay of NOESY pulse sequences, serious
      errors in measuring RNA proton distances are introduced.

PMID- 1373652
TI  - Sequential dephosphorylation of a multiply phosphorylated insulin receptor
      peptide by protein tyrosine phosphatases.
AB  - The question of whether protein tyrosine phosphatases (PTPases) dephosphorylate a
      multiply phosphorylated peptide in a random or ordered manner was investigated
      using the synthetic triphosphotyrosyl peptide TRDIY(P)ETDY(P)Y(P)RK,
      corresponding to the major sites of autophosphorylation of the insulin receptor,
      as a substrate for four purified PTPases. All four enzymes dephosphorylated the
      triphospho peptide to produce diphospho, monophospho, and nonphosphorylated
      forms. Partially dephosphorylated peptides were separated by reverse-phase HPLC,
      and the di- and monophospho peptides were collected and analyzed by solid-phase
      sequencing to determine the order of dephosphorylation of the three sites by each
      of the PTPases. The quantitative analysis of the signals for derivatives of
      tyrosine and phosphotyrosine generated at positions 5, 9, and 10 of the peptide
      showed that the low molecular weight human placental PTPase 1B preferentially
      dephosphorylated the two phosphotyrosines at positions 9 and 10 whereas the
      integral membrane enzyme CD45 (from human spleen) and the bacterially expressed
      rat LAR preferentially dephosphorylated the phosphotyrosine at position 5. A
      second low molecular weight enzyme, termed TCPTPase, did not display any
      specificity for a particular phosphotyrosyl residue. These results demonstrate
      that different PTPases exhibit a characteristic pattern of dephosphorylation of
      the triphospho peptide model substrate, raising the possibility that features in
      the primary structure surrounding the dephosphorylation site may contribute to
      substrate specificity.

PMID- 1373653
TI  - Involvement of the alpha chain in fibrin clot formation. Effect of monoclonal
      antibodies.
AB  - Murine monoclonal antibodies 9C3, 7B1, and 9E9 have been obtained using native
      human fibrinogen as the antigen. The antibodies reacted with the epitopes in the
      COOH-terminal domain of the A alpha chain. Fragmentation of the A alpha chain
      with plasmin, and, as in the case of the 9E9 epitope, with V8 protease, followed
      by isolation of the smallest reacting peptides, allowed the localization of the
      epitopes for 9C3, 7B1, and 9E9 to the amino acid sequences of alpha 240-268,
      alpha 425-440, and alpha 541-574, respectively. All three monoclonal antibodies
      strongly inhibited the rate of fibrin polymer assembly from monomers, both in the
      purified system and in the human plasma. The mechanism of this strong inhibition
      implied a rapid formation of fibrin protofibrils, followed by capping with IgG
      molecules of protofibrils containing approximately ten monomers. These
      observations demonstrated that certain regions in the COOH terminus of the alpha
      chain may play an important role in the assembly of a fibrin clot, presumably
      being involved in lateral aggregation of protofibrils.

PMID- 1373654
TI  - Luminescent/paramagnetic probes for detecting order in biological assemblies:
      transformation of luminescent probes into pi-radicals by photochemical reduction.
AB  - The spectroscopic methods of fluorescence polarization and electron paramagnetic
      resonance (EPR) are used to study order and orientation of extrinsically labeled
      protein elements of ordered biological systems. These methods generate
      complementary information about the order of the system, but a consistent
      quantitative interpretation of the related data is complicated because the
      signals arise from different donors. We introduce a new method that allows us to
      detect both signals from the same donor. Unsubstituted xanthene dyes (eosin,
      erythrosin, and fluorescein) were irradiated by laser light at their absorption
      maximum in the presence of different reducing agents. Due to photochemical
      reduction, the quinoidal structure of the xanthene ring is transformed into a
      semiquinone, and a pi-radical is formed having a characteristic EPR signal of an
      unpaired electron spin with proton hyperfine interactions. A strong EPR signal is
      observed from the dye in solution or when specifically attached to a protein
      following irradiation in the presence of dithiothreitol or cysteine. We applied
      this technique to the study of skeletal muscle fibers. The fluorescent dye
      (iodoacetamido)fluorescein was covalently attached to the reactive thiol of the
      myosin molecule in muscle fibers. Fluorescence polarization and EPR spectroscopy
      were performed on the labeled fibers in rigor. Both signals indicate a highly
      ordered system characteristic of cross-bridges bound to actin. Our use of the
      same signal donor for fluorescence and EPR studies of probe order is a promising
      new technique for the study of order in protein elements of biological
      assemblies.

PMID- 1373655
TI  - A new way to monitor by-pass restorations of electron transport in inhibited
      chloroplasts by cyclic electron flow cofactors--a study by modulated fluorimetry.
AB  - Inhibition of electron transport in broken chloroplasts by DBMIB, under light
      limiting conditions, is shown to be bypassed by PMS in a manner similar to the
      known effects of the phenylenediamine derivatives TMPD and DAD. These bypasses
      were demonstrated and further studied by modulated fluorimetry, monitoring DBMIB
      inhibition by the shift of the steady-state fluorescence towards the Fm level and
      the release of inhibition by a reverse shift together with establishment of a
      quenching effect by background far-red light. Comparative studies were also made
      with electron transport blocked by DCMU or BNT. A weak bypass by TMPD and a
      weaker one by PMS of the block created by DCMU was observed by modulated
      fluorimetry. The block created by BNT is similarly shown to be bypassed by TMPD
      but hardly or not at all by PMS. Bypass effects persisted even in the presence of
      ascorbate. It appears that, following reduction of the different cofactors by
      ascorbate in the stroma side, illumination caused the accumulation of a pool of
      oxidized cofactor molecules in the lumen, which is able to mediate electron
      transport between reduced plastoquinone and plastocyanin or P-700. The existence
      and the size of this pool were found to depend largely on the internal pH at the
      lumen, presenting an artificial system in which electron flow is controlled by
      the lumenal pH. The bypassing electron transport in the presence of DBMIB
      presumably avoids the participation of the cytochrome b6f complex. During its
      occurrence, there is also a strong imbalance in the activities of the two
      photosystems for linear electron flow, in favor of PS II. These experiments may
      thus serve to establish an in vitro model system for a future investigation of
      effects related to changes in the imbalance between the two photosystems and its
      regulation. Furthermore, this experimental system may also be utilized to study
      the role of the internal lumenal pH in control of photosynthesis.

PMID- 1373657
TI  - Electrophoresis and silver staining of rat urinary proteins including alpha 2u
      globulin (rat n II).
AB  - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining
      have been used to monitor the fractionation of rat urinary proteins by Amicon
      Centriprep C30/C10 ultrafiltration and to assess the purification of alpha 2u
      globulin, a laboratory animal allergen, precipitated by exhaustive dialysis.
      Factors influencing the protein composition of rat urine have been identified.
      Dialysis procedures have been evaluated for precipitation of alpha 2u-globulin
      and ultrafiltration used for further purification of the allergen.

PMID- 1373656
TI  - Toxin pharmacology of the ATP-induced hyperpolarization in Madin-Darby canine
      kidney cells.
AB  - The effects of Leiurus quinquestriatus hebraeus (LQH) venom, mamba venom, Buthus
      tamulus (BT) venom, purified apamin and synthetic charybdotoxin on the membrane
      hyperpolarization induced by extracellular ATP were examined in Madin-Darby
      canine kidney cells. For this we used a membrane potential probe (bisoxonol) to
      determine the potential variations. The relation between bisoxonal fluorescence
      and membrane potential was established by treating Madin-Darby canine kidney
      cells suspended in solutions containing various external sodium concentrations
      with gramicidin. Extracellular ATP induced a rapid hyperpolarization that was
      blocked by LQH venom and synthetic charybdotoxin. BT venom also blocked the
      response but at a much higher concentration than that of LQH. Mamba venom
      (Dendroaspis polylepis) and apamin did not modify the ATP-induced
      hyperpolarization. We concluded that the ATP induced hyperpolarization was due to
      the augmentation of the potassium conductance probably through Ca(2+)-activated
      K+ channels sensitive to charybdotoxin but not to mamba venom. The interaction
      previously described between charybdotoxin and dendrotoxin (the main toxin of
      mamba venom) was not observed in our case.

PMID- 1373658
TI  - The germinative zone produces the most cortical astrocytes after neuronal
      migration in the developing mammalian brain.
AB  - The origin of astrocytes of the mouse neocortex during the fetal and early
      postnatal periods as determined by immunocytological, autoradiographic, electron
      microscopic and antimitotic methods is described. Most astrocytes destined for
      the white matter and the infragranular cortical layers are derived from the
      transformation of radial glial cells between P0 and P10 with an inside-out
      pattern. This cell metamorphosis is not directly preceded by mitosis and involves
      the activation of the radial glial lysosomal apparatus. In opposition to recent
      hypotheses, our findings suggest that most astrocytes destined for the
      supragranular cortical layers are produced in the germinative zone after the
      migration of the infragranular neurons and themselves migrate afterwards to the
      upper cortex between E16 and the first postnatal days. These astrocytes do not
      display an intermediate stage of the radial glial cell and do not participate in
      the pattern of appearance of the deeper astrocytes. This second step of
      astrocytogenesis is a condition for normal cytoarchitectonic development and the
      maintenance of the supragranular layers, since the deprivation of the astrocytic
      equipment of the supragranular layers by an antimitotic drug drastically reduces
      the number of supragranular neurons.

PMID- 1373659
TI  - Synthesis and non-thrombogenicity of heparinoid polyurethaneureas.
AB  - Unsaturated polyurethaneureas were synthesized from 4,4'-diphenylmethane
      diisocyanate, 1,2-diaminopropane and polybutadiene containing hydroxyl groups at
      both ends of a chain. The polyurethaneureas were cast as a film and subsequently
      treated with N-chlorosulphonyl isocyanate to produce sulphamate and carboxylate
      groups on the film surface. The level of in vitro non-thrombogenicity increased
      with increasing degree of modification. The high blood compatibility is
      attributed to the low level of platelet stimulation and to heparinoid activity.
      It was observed that platelet stimulation depends on the surface structure of the
      original polyurethaneura, and that the heparinoid activity is related with the
      presence of sulphamate and carboxylate groups.

PMID- 1373660
TI  - Pharmacodynamics of pentamorphone during coronary artery bypass grafting in
      humans.
AB  - Pentamorphone is a new, highly potent opioid reported to have minimal
      cardiovascular effects in humans and a high therapeutic index in animals.
      Pentamorphone was injected intravenously (IV) as the sole anesthetic in 10
      patients with left ventricular ejection fractions greater than 0.35 who were
      undergoing elective coronary artery bypass grafting (CABG). After premedication
      with lorazepam, 40 micrograms/kg, and establishment of hemodynamic monitoring,
      pentamorphone was infused at a rate of 2 micrograms/kg/min until unconsciousness
      occurred (5.1 +/- 1.6 micrograms/kg). Anesthetic induction was accompanied by an
      average 30% decrease in systolic, diastolic, and mean arterial pressure (MAP), a
      19% decrease in heart rate (HR), but no change in cardiac output (CO) or
      pulmonary artery occlusion pressure. Five patients had a MAP less than 60 mm Hg
      after induction. Following incision, blood pressure, pulmonary artery occlusion
      pressure, and CO were unchanged from baseline but HR remained significantly
      lower. Despite additional pentamorphone (total dose 9.6 +/- 1.8 micrograms/kg), 6
      patients required thiopental and/or enflurane to control hypertension
      intraoperatively. When pentamorphone is used as the sole IV anesthetic in
      lorazepam-premedicated patients with normal or mildly impaired ventricular
      function, there is a high incidence of hypotension during induction, and poor
      control of hemodynamic responses to stimulation. Pentamorphone, 10 micrograms/kg,
      does not seem to offer any significant advantage over opioids currently used for
      anesthesia in patients undergoing CABG.

PMID- 1373661
TI  - Immunosuppressive effect of FK506 on experimental allergic neuritis in Lewis
      rats: change of T cell subsets.
AB  - The effect of a new immunosuppressant, FK506, on experimental allergic neuritis
      (EAN) was examined in Lewis rats. EAN was induced by inoculation with bovine
      peripheral myelin. The EAN rats were divided into two groups. FK506-treated EAN
      rats were prophylactically administered FK506 by injection into the peritoneal
      cavity at a dosage of 5.0 mg/kg/day for 13 days beginning the day after
      inoculation. The control EAN rats were injected with only saline solution. FK506
      prevented the development of EAN, histologically and clinically. In FK506-treated
      EAN rats, flow cytometric analysis of T cell subsets of the lymph nodes showed a
      significant decrease in W3/13 positive T cells on the 14th and 21st day and a
      decrease in W3/25 positive T cells on the 21st day after inoculation when
      compared with the control EAN rats. The percentage of OX-8 positive T cells were
      not significantly different between the two groups. Our results suggest that
      FK506 prevented the development of EAN by decreasing W3/13 and W3/25 positive T
      cells.

PMID- 1373662
TI  - A case of amylase-producing lung cancer.
AB  - A case of lung cancer with hyperamylasemia was studied. Small cell carcinoma was
      diagnosed histologically. The salivary gland and pancreas had no clinical
      involvement in the hyperamylasemia. Saliva-type amylase was dominant as observed
      from amylase isozyme patterns in the serum and tumorous tissue. Levels of amylase
      were higher in tumorous tissue than in normal lung tissue. Immunohistochemical
      study showed amylase localized in tumor cells. Observation of the ultrastructure
      revealed electron-dense granules in the cytoplasm of the tumor cells. Findings
      suggested that amylase was being produced by the lung cancer in this case.

PMID- 1373663
TI  - Rat brain acetylcholinesterase response to monocrotophos and abate.

PMID- 1373664
TI  - Age-related variation in urinary flow variables and flow curve patterns in
      elderly males.
AB  - A group of randomly selected males, over 50 years of age, was examined with
      regard to history and urinary flow rate. Originally, the group had comprised 93
      men without voiding problems, 15 who, although suffering from voiding problems,
      had not yet contacted their doctor, and 4 who had contacted their doctor because
      of voiding problems. Five years later the data were re-examined and 61 men were
      fully investigated again; in the remaining 51 patients only the history was
      updated. The 2 sets of data were evaluated separately as 2 cross-sectional
      investigations and as paired data sets by means of non-parametric statistical
      analysis. All uroflow variables were considered, i.e. Qmax, Qave, Qmax-time, Q
      "corrected", volume and the ratio Qmax/Qmax-time. In addition, the flow curve
      configuration was classified as normal or abnormal. When compared as 2 cross
      sectional investigations, the latter confirmed the results of the first. Qmax,
      Qave, Q "corrected" and volume decreased with advancing age, but no correlation
      could be demonstrated between Qmax-time and age. The flow curve pattern altered,
      so that a normal flow curve was seldom seem at an advanced age. Uroflow variables
      tended towards the abnormal with advancing years and symptoms increased
      concurrently. These changes were largely accepted by the elderly males. Thus the
      decision to operate for benign prostatic hyperplasia should be based on both
      history and urinary flow.

PMID- 1373665
TI  - Urinary flow rate in benign prostatic hypertrophy in relation to the degree of
      obstruction of the vesical outlet.
AB  - Forty men with bladder outflow obstruction from benign prostatic hypertrophy were
      investigated urodynamically by medium-fill water cystometry and pressure flow
      study. The most obstructed patients proved to be unstable. A positive link was
      found between the degree of obstruction, as assessed by the opening pressure
      (i.e. the detrusor pressure needed to start micturition), and the maximum
      mechanical power generated by the contracting bladder during voiding. What seems
      most striking, is that neither detrusor contraction velocity nor the urine flow
      rate fully mirrored the degree of obstruction--i.e. the opening pressure and the
      maximum contraction speed did not show a negative correlation, but rather a weak
      (though insignificant) positive link, and the flow rate decreased only slightly
      (not significantly) when obstruction increased. Such a surprising observation
      could be explained by the fact that prostatic obstruction produces both collagen
      infiltration into the bladder muscle (this affecting the spread of the
      depolarisation wave) and, at the same time, denervation supersensitivity. The
      latter actually yields a decrease in electrical resistance between the detrusor
      smooth muscle cells (and thereby an enhanced synchronisation of the detrusor
      contraction), which might be only partly cancelled by the effects of
      collagenosis.

PMID- 1373666
TI  - Identification of metastatic disease by T category, gleason score and serum PSA
      level in patients with carcinoma of the prostate.
AB  - Pre-operative serum prostate specific antigen (Tandem-R assay), T category,
      Gleason score and the metastatic (M1) status of a consecutive series of 60
      patients with newly diagnosed carcinoma of the prostate were studied
      prospectively. The results revealed that, of these variables, pre-operative serum
      PSA (greater than 100 ng/ml) was the single most important indicator of
      metastatic disease, with 100% predictive value. With this alone, 83.3% of M1
      disease could be correctly identified. For the remaining 17%, however, we
      advocate a high index of suspicion if the tumour is T3-T4 category on digital
      rectal examination (predictive value = 71.4%) and has a high grade with a Gleason
      score 8-10 (predictive value = 81%).

PMID- 1373667
TI  - An immunohistologic study of the epithelial components of 81 cases of thymoma.
AB  - Eighty-one cases of thymoma were studied immunohistologically with the use of
      three mouse monoclonal antibodies: one was specific for subcapsular-cortical, one
      for intra-cortical, and one for medullary epithelial cells. Twenty-eight (60.9%)
      of 46 polygonal cell thymomas were of the cortical type and 1 (2.2%) was of the
      medullary type. Ten (55.6%) of 18 spindle cell thymomas and 7 (41.2%) of 17 mixed
      cell thymomas were of the medullary type, and 1 (5.6%) of 18 spindle cell
      thymomas was of the cortical type. Fourteen (17.3%) of 81 thymomas were composed
      of epithelial cells that were triple positive immunologically; although these are
      unusual, they also may be present in the normal thymus. Based on these findings,
      triple-positive epithelium in the normal thymus consists of common stem cells
      that can differentiate into subcapsular-cortical, intra-cortical, and medullary
      epithelium; these cells may be the target cells for tumorigenesis. Epithelium in
      polygonal cell thymoma tends to differentiate into cortical epithelium, whereas
      epithelium in spindle and mixed cell thymomas differentiates into medullary
      epithelium.

PMID- 1373668
TI  - Establishment of human squamous carcinoma cell lines highly and minimally
      sensitive to bleomycin and analysis of factors involved in the sensitivity.
AB  - Human squamous carcinoma cell lines that were highly and minimally sensitive to
      bleomycin were established from clinical specimens and designated as SCCKN and
      SCCTF, respectively. Although these cell lines showed a similar growth doubling
      time in vitro, SCCTF was approximately ten times less sensitive to bleomycin than
      SCCKN. The bleomycin high and low sensitivities were stable even at the 70-cell
      passage level in vitro. In addition, nude mouse tumors produced by SCCTF were
      less sensitive to bleomycin that those produced by SCCKN, and the ratio of the
      mean tumor weight in bleomycin-treated mice to that in control mice was 89.2% in
      SCCTF and 18.8% in SCCKN. As compared with SCCKN, SCCTF also was less sensitive
      to peplomycin (5-fold), mitomycin C (2.3-fold), cis-diamine dichloroplatinum (2.5
      fold), and vincristine (6.5-fold). Analyses of low bleomycin sensitivity showed
      that SCCTF had an approximately 20% decreased cellular accumulation and retention
      of bleomycin, 1.2-fold increase of bleomycin hydrolase activity, elevated DNA
      repair activity, and increased poly(adenosine diphosphate-ribose) polymerase
      activity as compared with SCCKN.

PMID- 1373669
TI  - Computed tomography of sclerosing hepatocellular carcinoma.
AB  - We reviewed computed tomography (CT) in eight patients with sclerosing
      hepatocellular carcinoma who underwent resection. Dynamic CT was performed 25-40
      s (rapid phase) and 5-10 min (late phase) after injection of contrast medium.
      Most of the lesions were round and homogeneous. Tumors tended to show density
      equal to the liver. The relative density of the tumors in the rapid phase,
      however, tended to be higher than in other phases. A peripheral low-density area
      was absent. Dynamic CT was thus important in the diagnosis of sclerosing
      hepatocellular carcinoma.

PMID- 1373670
TI  - Binding parameters and idiotypic profile of the whole immunoglobulin and Fab'
      fragments of murine monoclonal antibody to distinct determinants of the human
      high molecular weight-melanoma associated antigen.
AB  - The nonspecific accumulation of radioactivity in bone marrow, liver, and spleen
      in patients with melanoma injected with radiolabeled whole IgG of anti-high
      molecular weight-melanoma associated antigen (HMW-MAA) monoclonal antibody (mAb)
      hampers the application of immunoscintigraphy to visualize melanoma lesions. This
      nonspecific background can be reduced by utilizing fragments which do not contain
      the Fc portion of anti-HMW-MAA mAb. Since the in vivo targeting to melanoma
      lesions of radiolabeled F(ab')2 and Fab' fragments of anti-HMW-MAA mAb is
      critically dependent on their binding parameters, we have analyzed the effect of
      fragmentation on the binding characteristics of the anti-HMW-MAA mAbs 225.28,
      763.74, and TP41.2. The three mAbs recognize distinct and spatially distant
      determinants with a heterogeneous distribution on the pool of HMW-MAA molecules
      synthesized by melanoma cells. The determinant recognized by mAb TP41.2 is
      detectable on a markedly smaller population of HMW-MAA molecules than those
      recognized by mAbs 225.28 and 763.74. 125I-labeled F(ab')2 fragments of the three
      mAbs displayed an immunoreactive fraction similar to that of the whole IgG, while
      Fab' fragments displayed a lower one. Fragmentation of mAbs 225.28 and TP41.2 to
      F(ab')2 produced a 2- and 1.5-fold reduction in their association constants but
      did not cause a significant change in that of mAb 763.74. Cleavage of F(ab')2
      fragments to Fab' fragments produced 2-, 40-, and 7-fold reductions in the
      association constants of mAbs 225.28, 763.74, and TP41.2, respectively. These
      changes qualitatively fit the predictions of theory for univalent and bivalent
      mAb binding, since mAbs 763.74 and TP41.2 appear to show bivalent binding to
      melanoma cells and mAb 225.28 to show univalent binding. The affinity constant of
      IgG, F(ab')2 and Fab' fragments of mAbs 225.28, 763.74, and TP41.2 displays an
      inverse relationship with the extent of their time-dependent release from the
      membrane of melanoma cells. Since no endocytosis of mAb could be detected, the
      latter results suggest that radioactivity remains bound to melanoma cells in vivo
      for a longer time following injection of F(ab')2 fragments than following that of
      Fab' fragments of each of the anti-HMW-MAA mAb tested. Radiolabeled Fab'
      fragments of mAbs 763.74 and TP41.2 displayed a marked reduction in their
      reactivity with some of the antiidiotypic mAb tested. The loss of some idiotopes
      is likely to be caused by changes in the conformation of the molecules associated
      with the fragmentation of IgG and by damage during the iodination procedure.

PMID- 1373671
TI  - Tumor selective reactivity of a monoclonal antibody prepared against a
      recombinant peptide derived from the DF3 human breast carcinoma-associated
      antigen.
AB  - The DF3 antigen is a member of a family of high molecular weight glycoproteins
      aberrantly expressed in malignant mammary epithelium. We have generated a
      monoclonal antibody (MAb), designated DF3-P, against a recombinant DF3/beta
      galactosidase fusion protein. Characterization of this MAb has demonstrated
      reactivity with immature precursors of DF3 antigen and not with the secreted
      form. These findings are in contrast to those obtained with MAb DF3, a previously
      described antibody with predominant reactivity against the mature glycoprotein.
      The finding that deglycosylation of secreted DF3 antigen with neuraminidase and
      endo-alpha-N-acetylgalactosaminidase is associated with increased MAb DF3-P
      reactivity provided additional support for the selectivity of this antibody
      against the protein core. Epitope mapping studies demonstrate that both the DF3-P
      and DF3 epitopes are located at a TRPAPGS domain in the 20-amino acid tandem
      repeat. The results of competition studies with synthetic peptides indicate that
      the proline in this domain is involved in both epitopes, while the potential
      glycosylation sites at threonine and serine may contribute to the differential
      reactivity of MAbs DF3 and DF3-P. Taken together, these findings suggest that
      both antibodies react with a similar epitope that is modified by the presence of
      carbohydrate moieties. The results of immunoperoxidase staining studies further
      demonstrate that while MAb DF3-P reacts with formalin-fixed sections of breast
      carcinomas, this antibody exhibits little if any reactivity with normal mammary
      epithelium. Selective expression of the DF3-P epitope in malignant breast cells
      may be useful in identifying this transformed phenotype.

PMID- 1373672
TI  - Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce
      differentiation of human breast cancer cells.
AB  - The HER-2/neu protooncogene (also called erbB-2) encodes a tyrosine kinase
      receptor for a polypeptide growth-regulatory molecule. Amplification and
      overexpression of the gene have been frequently observed in human adenocarcinomas
      and correlated with poor prognosis. To explore the potential of antibody therapy
      directed at the HER-2/Neu receptor, we have raised a panel of murine monoclonal
      antibodies to the human protein, and tested their effect on the tumorigenic
      growth of HER-2/neu-transfected fibroblasts in athymic mice. We previously
      reported that the i.p. injected antibodies either inhibited or accelerated the
      tumorigenic growth of HER-2/neu transfectants in athymic mice. Here we report
      that these opposing effects were induced also by i.v. injected antibodies, they
      lasted over 7 weeks, and were probably mediated by distinct epitopes on the
      receptor molecule. To understand the cellular mechanisms underlying antibody
      induced tumor inhibition, we tested the effect of the monoclonal antibodies on
      various cultured human breast cancer cells. Our analysis revealed that the tumor
      inhibitory antibodies specifically induced phenotypic cellular differentiation
      that included growth arrest at late S or early G2 phase of the cell cycle,
      markedly altered cytoplasm and nuclear morphology, synthesis and secretion of
      milk components (casein and lipids), and translocation of the HER-2/Neu protein
      to cytoplasmic and perinuclear sites. The extent of cellular differentiation by
      various antibodies could be correlated with their tumor-inhibitory potential,
      whereas a tumor-stimulatory monoclonal antibody or control immunoglobulin were
      completely inactive with respect to cellular differentiation. Taken together, our
      in vivo and in vitro studies correlate the tumor inhibitory potential of
      monoclonal antibodies to HER-2/Neu with their capacity to induce cellular
      differentiation in vitro. This observation may hold promise for immunotherapy of
      cancers that express the HER-2/neu oncogene.

PMID- 1373673
TI  - In vitro adsorption of a hydrophobic mutagen to gastrointestinal mucus
      glycoprotein (mucin) and dietary fibre.
AB  - The adsorption of mutagens by some dietary fibres has been suggested as one
      mechanism by which dietary fibres protect against colorectal cancer. It is
      thought that these dietary fibres carry the mutagen out of the digestive tract,
      decreasing the effective mutagen concentration to which epithelial cells are
      exposed. The ability of gastrointestinal mucin to alter the extent to which the
      hydrophobic mutagen 1,8-dinitropyrene (DNP) adsorbs in vitro onto the insoluble
      dietary fibre alpha-cellulose, was investigated. It was found that crude and
      purified human ileal mucins themselves adsorbed DNP and decreased the adsorption
      of DNP onto alpha-cellulose. Purified mucin which had been treated with trypsin
      also adsorbed DNP. These studies suggest that in the digestive tract there would
      be competition for the adsorption of DNP between mucin and insoluble dietary
      fibres, such as alpha-cellulose. This factor must be considered in predictions
      about the distribution of hydrophobic, mutagenic carcinogens in the digestive
      tract and their role in the etiology of colorectal cancer.

PMID- 1373674
TI  - Non-immunological release of histamine from rat mast cells elicited by
      antineoplastic agents.
AB  - We studied the histamine-releasing activity of several antineoplastic drugs on
      rat pleural and peritoneal mast cells. The drugs tested included the nitrogen
      mustards cyclophosphamide and ifosfamide, the nitrosourea carmustine, the
      triazene dacarbazine, the folic acid analogue methotrexate, the pyrimidine
      analogue cytarabine and fluorouracil, the vinca alkaloids vinblastine,
      vincristine and Vinorelbine, the epipodophyllotoxins etoposide and teniposide,
      and the enzyme L-asparaginase. Methotrexate, carmustine, fluorouracil,
      vinblastine and vincristine failed to elicit histamine release on rat mast cells.
      All of the other drugs evoked histamine release in both the presence and the
      absence of extracellular calcium, but ifosfamide, cytarabine and asparaginase
      induced a much lower release in the absence of this cation. The response elicited
      by cytarabine and etoposide was much higher in pleural than in peritoneal mast
      cells. These results indicate that some antineoplastic drugs may directly
      activate the release of histamine, which could contribute to some of their
      secondary effects.

PMID- 1373675
TI  - Improved diagnosis of carcinoid tumors by measurement of platelet serotonin.
AB  - Carcinoid patients are diagnosed biochemically on the basis of increased urinary
      excretion of 5-hydroxyindoleacetic acid (5-HIAA); urinary and platelet serotonin
      concentrations are considered to provide complementary information. Using
      established HPLC methods with fluorometric detection, we evaluated the clinical
      usefulness of measurements of urinary 5-HIAA and urinary, plasma, and platelet
      serotonin in 30 consecutive patients with histologically proven carcinoid tumors
      of fore-, mid-, and hindgut origin before treatment. Ten patients showed no signs
      of serotonin overproduction; 14 had increased concentrations of urinary 5-HIAA
      and platelet serotonin; and platelet serotonin, but not urinary 5-HIAA, was
      increased in 6. None had increased urinary 5-HIAA excretion without an increase
      in platelet serotonin content. In cases with high rates of tumor serotonin
      secretion, platelet serotonin reached a maximum and did not correlate with
      serotonin secretion rate, whereas urinary 5-HIAA was correlated. Increased
      platelet serotonin was correlated with increased plasma serotonin and with
      occurrence of carcinoid syndrome. Increased urinary serotonin, allegedly caused
      by increases in circulating 5-hydroxytryptophan, almost invariably coincided with
      increased platelet serotonin, but not necessarily with above-normal urinary 5
      HIAA excretion. From these results and long-term monitoring of three patients
      during treatment, we conclude that platelet serotonin is more sensitive than
      urinary 5-HIAA for detecting carcinoids that secrete only small amounts of
      serotonin.

PMID- 1373676
TI  - Persistence of increased amylase and lipase concentrations in acute pancreatitis.

PMID- 1373677
TI  - [Etiopathogenesis and therapeutic trends in adult T-cell leukemia associated with
      HTLV-I retrovirus].
AB  - HTLV-I (Human T-cell leukemia virus type I) has been the first human retrovirus
      identified and then associated with a definite pathological entity, a leukemic
      syndrome that specifically affects mature T-lymphocytes (ATL, adult T-cell
      leukemia), expressing CD3+, CD4+, CD8-, CD11- phenotype. This form of
      leukemia/lymphoma is endemic in southwestern islands of Japan, although at
      present the number of HTLV-I seropositive individuals has greatly increased, with
      a worldwide diffusion, following the expansion wave of the AIDS-associated HIV
      retrovirus. In fact, double seropositivity for both HIV and HTLV is frequently
      found among intravenous drug users. Although ATL leukemia or lymphoma occurs with
      a low frequency among HTLV-I seropositive individuals, it is likely that the
      evolution from a latent phase of infection to acute leukemia could be favoured by
      depression of immunosurveillance levels in the host. Therefore, special attention
      is required to prevent the diffusion of this retrovirus in adults, taking into
      consideration that newborn babies from seropositive mothers have to be considered
      at high risk for development of HTLV-I associated disease, on the basis of their
      immature immunocompetence.

PMID- 1373678
TI  - Association of genetic alterations of c-myc, c-fos, and c-Ha-ras proto-oncogenes
      in colorectal tumors. Frequency and clinical significance.
AB  - Using Northern and dot-blot analysis we examined normal and tumor tissue from 29
      patients with colorectal carcinomas for the expression and amplification of c
      myc, c-fos and c-Ha-ras proto-oncogenes. Overexpression of c-myc (6/24), c-fos
      (4/24), and c-Ha-ras (9/23) was found. For the c-fos proto-oncogene we also have
      observed decreased levels of expression in 13 percent (3/24) of the cases
      analyzed. Gene amplification appeared to be a rare event in these tumors and was
      found in 3/29 (10 percent) tumors for c-myc and in 1/29 (3 percent) for c-fos
      proto-oncogene. Curves for overall survival and for disease-free survival failed
      to show a significant tendency in these parameters to be poorer in tumors with
      alterations of gene expression for any of the proto-oncogenes analyzed. Despite
      the biologic importance of these genetic alterations in the etiology of
      colorectal tumors, levels of c-myc, c-fos, and c-Ha-ras gene expression
      separately or together cannot be considered as prognostic factors for clinical
      outcome of the disease.

PMID- 1373679
TI  - Supravital staining of synovial fluid with Testsimplets.
AB  - We explored the use of Testsimplet (TS) in synovial fluid (SF) analysis. TS is a
      glass slide coated with a dry mixture of methylene blue and cresyl violet, which
      in contact with one drop of SF provides a stained fresh preparation. We applied
      the TS to the study of 159 SFs of patients with different rheumatic diseases. In
      those SFs of patients with crystal-associated diseases, the crystal search was
      performed both on unstained preparations and with TS. TS was as good as the
      Wright's and Papanicolaou stain in characterizing SF cells, lupus erythematosus
      cells, and detection of occasional bacteria. TS allowed a better visualization of
      Reiter's cells, cartilage fragments, synovial villi, fat droplets, and fibrin.
      Crystals were identified in every TS of those patients with crystal-associated
      diseases. TS is a rapid and reproducible method of SF supravital staining.
      Crystals are well preserved for simultaneous examination with compensated
      polarized light.

PMID- 1373680
TI  - Whipple's disease involving the mesenteric lymph nodes diagnosed by fine-needle
      aspiration.
AB  - Although it traditionally presents with signs and symptoms of small intestine
      involvement, such as diarrhea and malabsorption, Whipple's disease (WD) can
      involve many other organs. Typically, WD diagnosis is established by biopsy of
      the small intestine. A case of WD, established by duodenal biopsy, in a 36-yr-old
      male is presented. This patient developed mesenteric lymphadenopathy, prompting
      computerized-tomography guided fine-needle aspiration (FNA), which showed typical
      features of WD. Electron microscopy (EM) studies confirmed the diagnosis. To our
      knowledge, this is the first reported case of lymph-node involvement in WD
      diagnosed by FNA biopsy.

PMID- 1373681
TI  - Urinary mutagenic activity in workers exposed to diesel exhaust.
AB  - We measured postshift urinary mutagenicity (mutu; n = 306 samples) on a
      population of railroad workers (n = 87) with a range of diesel exhaust exposures.
      Postshift urinary mutagenicity was determined by a sensitive microsuspension
      procedure using Salmonella strain TA98 +/- S9. Number of cigarettes smoked on the
      study day and urinary cotinine were highly correlated with postshift urinary
      mutagenicity. Diesel exhaust exposure was measured over the work shift by
      constant-flow personal sampling pumps. Respirable particle concentrations were
      adjusted for the contribution of environmental tobacco smoke, as estimated from
      nicotine concentration on treated filters. The relative ranking of jobs by this
      adjusted respirable particle concentration (ARP) was correlated with relative
      contact the job groups have with operating diesel locomotives. After adjustment
      for cigarette smoking (active and passive) in multiple regressions, there was no
      independent association of diesel exhaust exposure, as estimated by ARP, with
      postshift urinary mutagenicity among smokers or nonsmokers. An important finding
      is the detection of "baseline" mutagenicity in most of the nonsmoking workers.
      Despite the use of individual measurements of diesel exhaust exposure, the
      absence of a significant association in this study may be due to the low levels
      of diesel exposure, the lack of a specific marker for diesel exhaust exposure,
      and/or urinary mutagenicity levels from diesel exposure below the limit of
      sensitivity for the mutagenicity assay.

PMID- 1373682
TI  - Alpha 2-macroglobulin: a protein at the interface of fibrinolysis and cellular
      growth regulation.

PMID- 1373683
TI  - An A gamma globin promoter (four base-pair deletion) mutant shows linked
      polymorphic changes throughout the A gamma gene.
AB  - The A gamma fetal globin genes from a large Australian kindred with nondeletional
      A gamma hereditary persistence of fetal hemoglobin (HPFH) were cloned and
      sequenced. The -198 T----C mutation (British type HPFH) was demonstrated upstream
      of the A gamma gene on one allele. On the other allele, a 4-deletion was
      identified -222 to -225 bp upstream from the cap site. The 4-bp deletion allele
      was associated with a number of variations in the A gamma gene sequence: anA
      gamma T transition, in the second exon (T----C at +402 relative to the cap site);
      a HindIII polymorphism in the second intron; and a G gamma-like sequence in the
      3' untranslated region (TCAC in place of CTCT, creating a SacI site). An
      association between the -222 to -225 deletion, the A gamma T polymorphism, and
      the second intron HindIII polymorphism has previously been reported. In addition,
      linkage of the HindIII polymorphism with the G gamma-like sequence in the 3'
      untranslated region of A gamma has also been described. The case described here
      is unique, with all four changes present in the one A gamma gene. It is also
      noteworthy because there is simultaneous occurrence of high (HPFH) and low (-222
      to -225 deletion) expression mutants in the same patient. Despite the presence of
      the 4-bp deletion, the resulting hematological phenotype remained that of HPFH.
      When the 4-bp deletion promoter was studied in a K562-cell transient expression
      assay, there was found to be no statistically significant reduction in activity
      compared to the control A gamma promoter. The possible reasons for the observed
      differences between the in vivo and in vitro activity of this mutation are
      discussed.

PMID- 1373684
TI  - Dexamethasone inhibits tumor necrosis factor-induced granulocyte colony
      stimulating factor production in human endothelial cells.
AB  - Dexamethasone (10(-5)-10(-7) M) is able to suppress the tumor necrosis factor
      (TNF)-induced production of granulocyte colony-stimulating factor (G-CSF) in
      human umbilical vein endothelial cells (HUVEC). Using Western-blot analysis and
      bioassay for the evaluation of G-CSF protein and activity, a significant decrease
      in TNF-induced production could be found in cells cultured in the presence of
      dexamethasone as compared to TNF stimulation in the absence of dexamethasone. No
      inhibition by dexamethasone was seen in endothelial cells stimulated with
      interleukin 1 beta (IL-1 beta; 10 U/ml). Addition of IL-1 to cultures stimulated
      with TNF in the presence of dexamethasone could overcome the inhibitory effects
      of corticosteroids. Suppression of G-CSF production can, at least in part,
      explain the functional abnormalities of granulocytes found in patients treated
      with glucocorticosteroids.

PMID- 1373685
TI  - Interactions among colony-stimulating factors, IL-1 beta, IL-6, and kit-ligand in
      the regulation of primitive murine hematopoietic cells.
AB  - We have investigated the regulation of primitive murine hematopoietic progenitors
      by the cytokines interleukin 1 (IL-1), interleukin 6 (IL-6), and kit-ligand (KL).
      Individually these cytokines have a limited ability to stimulate the growth of
      high proliferative potential colony-forming cells (HPP-CFC) from 5-fluorouracil
      (5-FU)-purged bone marrow, but in combination these cytokines demonstrate
      synergism in promoting the growth of HPP-CFC. Furthermore, IL-1, IL-6, and KL,
      alone or in combination, synergized with the colony-stimulating factors (CSFs)
      granulocyte CSF (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM
      CSF), or interleukin 3 (IL-3) in clonal and liquid cultures of 5-FU-purged bone
      marrow. The pattern of HPP-CFC growth that was observed with 40 different
      cytokine combinations demonstrated the unique roles of IL-1, IL-6, and KL in the
      regulation of HPP-CFC proliferation. Short-term liquid cultures (delta-cultures),
      with secondary recloning, of 5-FU-purged bone marrow were stimulated to greatly
      expand the numbers of progenitor cells generated in response to cytokine
      stimulation. The greatest expansion, over 1800-fold, of the more mature
      progenitor compartments took place in delta-cultures stimulated with IL-1, IL-6,
      and KL plus IL-3. However, the combination of IL-1 and IL-6 plus KL was optimal
      in expanding HPP-CFC, increasing their numbers by 700-fold. The ability to expand
      early progenitor cells in delta-cultures was further demonstrated by the greater
      than 100-fold expansions of day-12 spleen colony-forming units (CFU-S) by the
      synergistic interactions of IL-1 with IL-3 or KL.

PMID- 1373686
TI  - Anti-IL-6 antibodies suppress myeloid cell production and the generation of CFU-c
      in long-term bone marrow cultures.
AB  - Interleukin 6 (IL-6) is one of several hemopoietic growth factors produced by
      stromal cell lines derived from the adherent layer of long-term bone marrow
      cultures (LTBMCs). To evaluate the potential role of IL-6 in stromal cell
      dependent myelopoiesis, we established LTBMCs and verified that IL-6 mRNA is
      transcribed by heterogeneous adherent cell layers and that IL-6 protein is
      present in culture supernatants. Established LTBMCs were then depleted of IL-6 by
      using a specific neutralizing monoclonal antibody (mAb). Cultures treated for 2-3
      weeks with anti-IL-6 mAb showed decreased production of maturing myeloid cells
      and colony-forming progenitor cells (colony-forming units in culture, CFU-c) but
      not stem cells (spleen colony-forming units, CFU-s). In parallel experiments, it
      was also found that the addition of IL-6 to LTBMCs stimulated a marked increase
      in total cell production, CFU-c, and day-8 CFU-s. In sum, it appears that
      endogenous production of IL-6, although limiting, is essential for the normal
      level of myelopoiesis associated with stromal cell function in LTBMCs.

PMID- 1373687
TI  - Human interleukin (IL)-9 specifically stimulates proliferation of CD34+++DR+CD33-
      erythroid progenitors in normal human bone marrow in the absence of serum.
AB  - The cDNA encoding human interleukin (IL)-9 has recently been cloned and the
      recombinant molecule found to enhance erythroid colony formation in vitro by bone
      marrow, peripheral blood, and cord blood cells. In our present report,
      recombinant human (rhu) IL-9 was evaluated, alone and in combination with other
      cytokines, for its effect on colony formation by erythroid progenitor (erythroid
      burst-forming units, BFU-E) and precursor (erythroid colony-forming units, CFU-E)
      cells in low density (LD), nonadherent LD density T-lymphocyte-depleted (NALT-),
      and immunofluorescence-sorted CD34+++DR+ and CD34+++DR+CD33- cells from normal
      human bone marrow. When highly enriched CD34+++DR+ and CD34+++DR+CD33- cells were
      plated at 200 and 100 cells/ml in the presence of 5% (vol/vol) 5637-cell
      conditioned medium and erythropoietin (Epo) under serum-containing conditions, 46
      and 51 day-14 BFU-E were observed, respectively. The enhancing effect of rhuIL-9
      was similar to that of 5637 CM on colony formation by Epo-dependent BFU-E and CFU
      E in these enriched sorted CD34+++DR+ and CD34+++DR+CD33- cells under serum
      containing and serum-depleted culture conditions. No significant synergistic or
      additive effect of rhuIL-9 was noted when used in conjunction with rhu
      interleukin 3 (rhuIL-3), rhu interleukin 6 (rhuIL-6), and/or rhu granulocyte
      macrophage colony-stimulating factor (rhuGM-CSF) under the same culture
      conditions. The cloning enhancing effect elicited by human IL-9 is Epo dependent,
      although IL-9 alone sustains the survival of erythroid progenitor cells in vitro,
      as assessed by delayed additions of Epo to the cultures. The ability of human IL
      9 to stimulate BFU-E and CFU-E colony formation using low numbers of highly
      enriched progenitor cells in serum-depleted conditions demonstrates the direct
      effect of IL-9 on erythroid progenitors and implicates its potential role in the
      enhancement of erythropoiesis.

PMID- 1373688
TI  - Effects of anti-CD33 blocked ricin immunotoxin on the capacity of CD34+ human
      marrow cells to establish in vitro hematopoiesis in long-term marrow cultures.
AB  - Human marrow cells that express the CD34 antigen but lack CD33 are able to
      initiate sustained, multilineage in vitro hematopoiesis in long-term Dexter
      cultures and are believed to include the primitive stem cells responsible for
      effecting long-term hematopoietic reconstitution in vivo following marrow
      transplantation. In studies described in this report we investigated the effects
      of a novel anti-CD33 immunotoxin on the clonogenic potential of normal human
      CD34+ marrow cells and on the ability of these cells to initiate hematopoiesis in
      two-stage Dexter cultures (long-term marrow cultures, LTMC). This immunotoxin
      (anti-CD33-bR), shown previously to kill both clonogenic myelogenous leukemia
      cells and normal mature myeloid progenitor cells (granulocyte-macrophage colony
      forming units, CFU-GM), consists of an anti-CD33 monoclonal antibody conjugated
      to purified ricin that has been modified by blocking the carbohydrate binding
      domains of the ricin B-chain to eliminate nonspecific binding. For our studies,
      normal CD34+ human marrow cells were isolated from the light-density (less than
      1.070 g/ml) cells of aspirated marrow by positive selection with immunomagnetic
      beads linked to the monoclonal antibody K6.1. These cell isolates were highly
      enriched with both multipotential and lineage-restricted clonogenic,
      hematopoietic progenitors (mixed lineage colony-forming units, CFU-Mix; CFU-GM;
      and erythroid burst-forming units, BFU-E) which constituted greater than or equal
      to 20% of the cells. Recovery of clonogenic progenitors from these CD34+ cell
      preparations, following treatment with anti-CD33-bR (10 nM), was reduced by
      greater than or equal to 85% for CFU-GM and 20%-40% for CFU-Mix and BFU-E.
      However, the capacity of these cells to initiate hematopoietic LTMC was
      preserved. Indeed, the production of high proliferative potential (HPP) CFU-GM,
      BFU-E, and CFU-Mix in cultures seeded with 10(5) anti-CD33-bR-treated CD34+
      marrow cells was substantially greater than that observed in LTMC seeded with
      equivalent numbers of untreated CD34+ cells. Moreover, concentrations of long
      term culture initiating cells in CD34+ cell isolates, quantified by a limiting
      dilution technique, were found to be increased following anti-CD33-bR treatment.
      These findings support the potential usefulness of anti-CD33-bR for in vitro
      marrow purging or in vivo treatment to eliminate CD33+ leukemic clones, while
      sparing normal CD34+/CD33- stem cells that support normal hematopoiesis and
      hematopoietic reconstitution in vivo.

PMID- 1373689
TI  - Retinoic acid acts to neutralize the inhibitory effect of granulocyte-macrophage
      colony-stimulating factor (GM-CSF) on alkaline phosphatase activity of
      neutrophils that is induced by granulocyte colony-stimulating factor (G-CSF).
AB  - Granulocyte colony-stimulating factor (G-CSF) is known to act on the neutrophilic
      granulocytes from chronic myelogenous leukemia (CML) patients to induce
      neutrophil alkaline phosphatase (NAP) activity. Gamma-interferon (IFN-gamma) and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) have been reported to
      suppress NAP induction with G-CSF. We confirmed that this inhibitory effect of GM
      CSF is accompanied by the decrease of the NAP mRNA level. Moreover, we found that
      the simultaneous addition of retinoic acid completely neutralized this inhibitory
      effect of GM-CSF. Recovery of the NAP activity brought about by the retinoic acid
      was also accompanied by the increase of NAP mRNA level. These results indicate
      that retinoic acid neutralizes the inhibitory effect of GM-CSF on the induction
      of NAP activity through the change of the NAP mRNA level.

PMID- 1373690
TI  - Recombinant GM-CSF/IL-3 fusion protein: its effect on in vitro human
      megakaryocytopoiesis.
AB  - An evaluation of the effectiveness of a genetically engineered recombinant
      granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin 3 (IL-3)
      fusion protein (FP) as a means of delivering cytokine combinations to
      megakaryocyte (MK) progenitor cells was performed, utilizing a serum-depleted
      clonal assay system and a long-term bone marrow culture system. The effects of
      the FP, alone and in combination with a variety of other cytokines, on the
      primitive MK progenitor cell, the megakaryocyte burst-forming unit (BFU-MK), and
      the more differentiated megakaryocyte colony-forming unit (CFU-MK) were assessed.
      Subpopulations of bone marrow cells (CD34+ DR- for BFU-MK and CD34+ DR+ for CFU
      MK) served as sources of these two classes of MK progenitor cells. The FP was
      equivalent to a combination of optimal concentrations of GM-CSF and IL-3 in
      promoting both the number and size of BFU-MK-derived colonies. The GM-CSF/IL-3
      combination, however, promoted the formation of far greater CFU-MK-derived
      colonies than did the FP alone. The size of MK colonies formed in the presence of
      the FP or GM-CSF/IL-3 was similar. The ability of the FP to stimulate BFU-MK- but
      not CFU-MK-derived colony formation was also further augmented by the addition of
      interleukin 1 alpha (IL-1 alpha). The addition of c-kit ligand (KL) increased
      both FP-stimulated CFU-MK- and BFU-MK-derived colony numbers but only BFU-MK
      derived colony size. In addition, the FP alone sustained long-term
      megakaryocytopoiesis in vitro to a level equivalent to that of the GM-CSF/IL-3
      combination and was superior in this regard to either GM-CSF or IL-3 alone. These
      data indicate that FP is capable of supporting various stages of human
      megakaryocytopoiesis. We conclude that such genetically engineered molecules as
      the FP may prove to be effective means of pharmacologically delivering the
      biological effects of specific cytokine combinations.

PMID- 1373691
TI  - Expression of stem cell factor and c-kit mRNA in cultured endothelial cells,
      monocytes and cloned human bone marrow stromal cells (CFU-RF).
AB  - Previously, we have shown that conditioned medium from a subpopulation of human
      marrow stromal cells (CFU-RF) contain an activity able to stimulate the growth of
      macroscopic epo-dependent erythroid colonies. The ligand for the product of the c
      kit proto-oncogene (also known as stem cell factor or SCF), among other
      activities, has been reported to have similar effects on erythroid colony growth.
      We have also presented data showing that SCF together with phytohemagglutinin
      stimulated leukocyte conditioned medium can stimulate erythroid colony growth in
      the presence of antibodies to erythropoietin. Using the human SCF cDNA probe (K.
      Zsebo, Amgen Inc.) we now show that cells derived from CFU-RF colonies express
      SCF but not c-kit. Human umbilical vein endothelial cells were also found to
      express SCF and this expression was increased by addition of monocyte
      supernatant, IL-1 beta or thrombin. Cells of the human erythroleukemia cell line
      HEL were found to express c-kit but not SCF. Neither c-kit nor SCF mRNA were
      detected in phytohemagglutinin-stimulated lymphocytes. Together, these data
      support the view that the behaviour of proliferating erythroid stem cells in the
      marrow, which may express c-kit, could be regulated by membrane-bound SCF present
      on surrounding stromal cells.

PMID- 1373692
TI  - The CD34+ cell fraction in bone marrow and blood is not universally predictive of
      CFU-GM.
AB  - We have measured the presence of granulocyte-macrophage colony forming cells (CFU
      GM) and CD34+ cells in blood and bone marrow. We have compared these
      hematopoietic cell assays using regression analysis. We have found that under the
      limited and specific case of blood cells from an individual recovering from myelo
      suppressive chemotherapy, the fraction of cells that is CD34 positive is
      predictive of the number of granulocyte-macrophage colonies (CFU-GM) which will
      grow. This result is in agreement with published data. We have found, however,
      that in bone marrow aspirates, or in the blood of individuals recovering from
      cyclophosphamide chemotherapy and receiving either granulocyte-macrophage colony
      stimulating factor (G-CSF) or folinic acid (FA) therapy, there is poor
      correlation between CD34+ cell fraction and CFU-GM. Accordingly, the use of CD34+
      fraction cannot be relied upon to substitute for the CFU-GM assay in assessing
      the hematopoietic cell content of blood or bone marrow samples.

PMID- 1373693
TI  - [The sequelae of transient myocardial ischemia in chronic experiments].
AB  - Reversible short-term and local myocardial ischemia in non-anaesthetized dogs
      involved a functional (if changing the activity of CPK) and morphologic
      aftereffect. At the same time it is possible to find some mechanisms of
      compensation (in chronic experiment).

PMID- 1373694
TI  - Maternal alpha-2-macroglobulin levels and fetal growth in Guatemala.
AB  - Maternal serum alpha-2-macroglobulin (alpha 2M) levels were measured at the time
      of delivery in 244 women in the central highlands of Guatemala. Significantly
      higher alpha 2M levels were found in thin women and in poor women. In multiple
      regression analysis controlling for gestational age, race, sex, maternal triceps
      skinfold thickness and socioeconomic status, high alpha 2M levels were
      significantly associated with decreased birthweight. These findings agree with
      those in a predominantly black population in the United States and extend the
      relationship between alpha 2M and decreased birthweight to a developing country.

PMID- 1373695
TI  - The nontransformed progesterone and estrogen receptors in gastric cancer.
AB  - Contents of the progesterone receptors (PgR) and estrogen receptors (ER) in 18
      gastric adenocarcinoma tissues were determined using both the dextran-coated
      charcoal (DCC) assay and enzyme immunoassay (EIA). PgR were found in 15 cancer
      tissues (range, 1.0-58.8 fmol/mg protein) and 12 normal mucosal tissues (range,
      1.4-26.8 fmol/mg protein) by DCC assay, whereas only 6 cancer tissues (ranged,
      0.2-3.3 fmol/mg protein) and 7 normal mucosal tissues (range, 0.1-0.8 fmol/mg
      protein) had measurable PgR by EIA analysis. Similar results were observed for
      ER. DCC assay found ER in 12 cancer tissues (range, 2.9-112.6 fmol/mg protein)
      and 12 normal mucosal tissues (range, 1.2-36.6 fmol/mg protein), whereas EIA
      measured ER in 16 cancer tissues (range, 0.1-3.5 fmol/mg protein) and 15 normal
      mucosal tissues (range, 0.1-4.8 fmol/mg protein). No significant correlation
      between DCC and EIA was observed for either PgR or ER. DCC assay and its modified
      procedures including 5% DCC stripping of cytosol and/or the addition of sodium
      molybdate in buffer were simultaneously measured in 5 gastric adenocarcinoma
      tissues and 1 gastritis cystica polyposa tissue (a precancerous lesion). Higher
      receptor levels were found by the modified procedures than by conventional
      method. Using the DCC procedure with addition of sodium molybdate in buffer for
      receptor analysis, PgR and ER were found in gastric tissues in six patients, with
      significantly increased levels of measurable PgR. The results suggest that PgR
      and ER may be involved in the physiology of normal and gastric cancer tissues;
      their clinical implications are worthy of further study.

PMID- 1373697
TI  - A new look at the mechanisms of healing of peptic ulcers.

PMID- 1373696
TI  - Differential expression of collagen types I, III, and IV by fat-storing (Ito)
      cells in vitro.
AB  - It has been observed that Ito cells in vitro undergo phenotypical changes
      ("activation") similar to those noted in vivo during the development of liver
      fibrosis. Because conflicting data have been published on the amount and
      different types of collagens synthesized by Ito cells in vitro, collagen
      biosynthesis was studied at different "activation" stages on both the protein and
      RNA levels. Immunoprecipitation of endogenously labeled collagen showed that
      freshly isolated ("resting") Ito cells synthesize mainly collagen type IV.
      Collagen type I was hardly detectable in the earlier stage of primary culture,
      but it clearly increased starting 5 days after isolation. Compared with the basal
      rates measured at day 3 after isolation, collagen types I, III, and IV increased
      7.5-, 3.5-, and 1.9-fold, respectively, until day 7 of culture. The relative
      ratios of newly synthesized collagen types I, III, and IV on day 3 after
      isolation were approximately 10%, 45%, and 45%, and they changed to 45%, 40%, and
      15% on day 7 of primary culture. On the RNA level, freshly isolated Ito cells
      contained predominantly collagen type IV- and III-specific transcripts. By
      densitometric analysis, collagen type I, III, and IV messenger RNAs increased 6.2
      , 2.5-, and 3.5-fold from day 3 to day 7 of primary culture. These results
      indicate that "resting" Ito cells synthesize primarily collagen type IV and could
      be a major cellular source of this basement membrane component in normal liver.
      "Activated" Ito cells switch to the synthesis of the interstitial collagen types
      I and III and might be mainly responsible for the accumulation of collagen types
      I and III in fibrotic liver diseases.

PMID- 1373698
TI  - Diagnosing a diagnostic study--lipase/amylase ratio.

PMID- 1373699
TI  - Treatment of malignant strictures of the cervical esophagus by endoscopic
      intubation using modified endoprostheses.
AB  - Endoscopic intubation has traditionally been considered unsuitable as a means of
      palliating cervical esophageal carcinomas involving or within 2 cm of the
      cricopharyngeus sphincter muscle because of the potential problems of foreign
      body sensation and proximal prosthesis migration. We attempted to palliate eight
      such patients, three of whom had tracheo-esophageal fistulas by the endoscopic
      placement of modified Celestin endoprostheses; the floppy funnel of the
      prosthesis was positioned above the cricopharyngeus in the hypopharynx.
      Prosthesis placement and fistula occlusion was possible in all patients. Six
      patients had a significant long-term improvement in their dysphagia, managing a
      semi-solid (5 patients) or liquid diet (1 patient); two patients did not improve,
      despite accurate prosthesis placement, because of marked tracheal aspiration. Six
      patients reported no foreign body sensation; one patient had minor discomfort,
      and another moderate throat discomfort. Distal prosthesis migration occurred in
      two patients (replaced in 1 patient). Endoscopic intubation of high cervical
      esophageal carcinomas with specially modified endoprostheses is feasible and can
      provide worthwhile palliation of dysphagia and symptoms due to a tracheo
      esophageal fistula. Foreign body sensation and proximal prosthesis migration did
      not prove troublesome.

PMID- 1373700
TI  - Recanalization of tube overgrowth: a useful new indication for laser in
      palliation of malignant dysphagia.
AB  - Overgrowth of an esophageal prosthesis by cancer is a late complication of
      insertion which presents a difficult management problem. We have treated 14 such
      patients; 9 had Celestin tubes and 5 Atkinson tubes in situ for a median of 7
      months. The median patient age was 75 years; 3 had squamous cell carcinomas and
      11 adenocarcinomas; 12 were at the lowest thoracic esophagus or cardia, and 2
      were anastomotic. Eleven tubes were overgrown at the top, two at the bottom only,
      and one at both ends. Dysphagia was graded from 0 to 4 (0 = normal; 4 = dysphagia
      for liquids). All patients but one improved with treatment. The median pre
      treatment grade was 4 (range, 2 to 4) and post-treatment was 2 (0 to 3). This
      improvement was significant (p less than 0.01) Wilcoxon-signal rank). Most
      patients required only one or two endoscopies. The median survival was 9 weeks
      from first laser session (range, 3 to 36 weeks). We feel these results justify
      laser treatment in most patients in whom cancer overgrowth causes blockage of an
      esophageal prosthesis.

PMID- 1373701
TI  - [Neuroendocrine tumors of the gastrointestinal tract. Part 2: Current therapeutic
      concepts].
AB  - When diagnosed, the greater proportion of functioning endocrine tumors have
      already metastasized. As a result, the primary aim of treatment--complete
      surgical removal of the growth--is possible in only a small number of patients.
      This gives considerable importance to palliative treatment. Interferons and
      somatostatin are the substances in the forefront of therapeutic interest today,
      cytostatic chemotherapy having proved largely ineffective and associated with
      considerable side effects. A feature common to interferons and somatostatin is
      the fact that they are much more likely to achieve a subjective improvement in
      clinical symptoms rather than objective remission. However, this is not
      disadvantage, since, in view of the slow growth of these tumors, quality of life
      is determined by controlling endocrine activity and not by debulking tumor mass.

PMID- 1373702
TI  - Is the follow-up of patients operated on for gastric carcinoma of benefit to the
      patient?
AB  - In patients operated on for gastric carcinoma, the main purpose of a follow-up
      program is to diagnose recurrent disease and initiate treatment at an early
      stage. One hundred and ninety-seven consecutive patients were studied, 43 of whom
      had not received a resection (27%). Resections were carried out in 144 patients,
      in either palliative (N = 20), or curative (N = 122) intent. The follow-up
      program included visits to the outpatient clinic at one month, six months, one
      year, and every year during the five post-operative years. Shorter intervals were
      employed as indicated by the functional or general status of the patients. One
      patient has been lost to follow-up. In palliative surgery, median survival was 3
      months in patients undergoing laparotomy, 6 months following palliative surgery
      without resection, and 8 months following palliative resection. In patients who
      underwent curative resection, 65 are still alive without recurrent disease (57%).
      Thirty-six of them have been followed-up for more than 5 years. Seven patients
      died without recurrence. Of 42 patients with recurrence, 10 underwent a
      reoperation. The only resection was performed for liver metastasis. This patient
      died 14 months later. Survival in the 9 other patients did not exceed 6 months.
      This experience suggests that a follow-up program of patients operated on for
      gastric carcinoma is disappointing.

PMID- 1373703
TI  - Localization and cellular source of the extracellular matrix protein tenascin in
      normal and fibrotic rat liver.
AB  - The distribution and the cellular source of the novel extracellular matrix
      glycoprotein tenascin were studied in normal and fibrotic rat liver. Cryostat
      sections of normal rat livers, livers of rats treated with intraperitoneal
      injections of CCl4 and 4-day-old and 8-day-old primary fat-storing cell cultures
      were stained for tenascin and desmin using an immunoperoxidase procedure or a
      double-label immunofluorescence technique. Fat-storing cell cultures were
      metabolically labeled with 3H-proline. Radiolabeled proteins were
      immunoprecipitated from the supernatant with antitenascin antiserum and subjected
      to polyacrylamide gel electrophoresis. In normal rat livers, tenascin was
      detected discontinuously along the sinusoids, whereas portal tracts were devoid
      of staining. In fibrotic rat livers, tenascin was preferentially expressed in
      areas of cell damage, in slender septa or at connective tissue-parenchymal
      interfaces. The middle region of broad septa was negative. Desmin-positive fat
      storing cells accumulated in areas strongly immunoreactive for tenascin, and
      double-label immunofluorescence showed cells positive for both tenascin and
      desmin. In fat-storing cell cultures, both intracellular positivity for tenascin
      and staining of extracellular fibers were seen. Gel electrophoresis of
      immunoprecipitated proteins revealed two major and three minor bands with
      molecular weights consistent with tenascin. We conclude that tenascin is a
      component of the extracellular matrix of both normal and fibrotic rat livers. The
      strong expression of tenascin in areas of cell damage, in "early" septa or at
      septal-parenchymal interfaces, in contrast to its absence from the middle region
      of mature septa, suggests a role in early matrix organization. Fat-storing cells
      synthesize and secrete tenascin.

PMID- 1373704
TI  - Glycolipids carrying Le(y) are preferentially expressed on small-cell lung cancer
      cells as detected by the monoclonal antibody MLuC1.
AB  - The monoclonal antibody MLuC1, which reacts strongly with a high percentage of
      small-cell lung cancers (SCLC), as well as with various human carcinomas, has
      been used to immunochemically characterize the recognized epitope (CaMLuC1). To
      this aim 3 different approaches were adopted: (1) immunoblotting/immunostaining
      of extracts from various tumor-cell lines; (2) inhibition of binding by purified
      oligosaccharides; (3) direct binding to oligosaccharide-protein conjugates. All
      of these experiments indicate that CaMLuC1 is present on the Le(y) blood-group
      structure heterogeneously expressed on various glycoproteins and glycolipids. The
      expression of the glycoconjugates carrying Le(y) was then analyzed on breast and
      lung cancers and on their normal counterparts. Our overall results suggest that
      SCLC produce Le(y)-active glycolipids in higher amounts compared to other tumors
      of the same or of a different oncotype, as well as normal lung cells, thus
      indicating an SCLC-specific modification of the glycosylation pathways.

PMID- 1373705
TI  - Hematopoietic growth factors secreted by seven human pleural mesothelioma cell
      lines: interleukin-6 production as a common feature.
AB  - Seven mesothelioma cell lines, established from patients with pleural
      mesothelioma, exhibited substantial heterogeneity regarding in vitro morphology
      and growth characteristics. Media conditioned by these cell lines and by MeT5A
      normal mesothelial cells were examined for (i) colony formation on human bone
      marrow cells, (ii) hematopoietic growth-factor content and (iii) mitogenic
      activity on mesothelioma cells. Colony-stimulating activity was produced only by
      the ZL34 cell line. Analysis of conditioned media by ELISA revealed that all
      mesothelioma cell lines constitutively produced IL-6, while the MeT5A normal
      mesothelial cells did not; in addition, GM-CSF and G-CSF were detected in the
      supernatant of the ZL34 cell line. Using a 3H-thymidine incorporation assay, we
      showed that all mesothelioma cell lines produced mitogenic activity in the
      culture supernatant, in contrast to the MeT5A normal mesothelial cells. The
      mitogenic effect of the hematopoietic growth factors detected in mesothelioma
      culture supernatants was tested on mesothelioma cells and on MeT5A normal
      mesothelial cells: IL-6, GM-CSF and G-CSF did not stimulate any DNA synthesis.
      Our results suggest that these hematopoietic growth factors do not act as
      autocrine growth factors. A common feature of this panel of mesothelioma cell
      lines is the production of IL-6; although the biological significance of the
      aberrant production of cytokines by mesotheliomas remains unclear, IL-6 might be
      involved in paraneoplastic syndromes such as thrombocytosis.

PMID- 1373706
TI  - Enzymatic basis of sugar structures of alpha-fetoprotein in hepatoma and
      hepatoblastoma cell lines: correlation with activities of alpha 1-6
      fucosyltransferase and N-acetylglucosaminyltransferases III and V.
AB  - alpha-Fetoproteins (AFPs) were purified from 2 hepatoma cell lines (Hep G2 and
      HuH-7) and a hepatoblastoma cell line (HuH-6), and the structures of
      pyridylaminated (PA) derivatives of their sugar chains were analyzed by HPLC.
      Simultaneously, the activities of alpha 1-6 fucosyltransferase (alpha 1-6FT) and
      N-acetylglucosaminyltransferase III (GnT-III), IV (GnT-IV) and V (GnT-V) were
      assayed in these cell lines. For all 3 cell lines the major sugar chain detected
      was a fucosylated biantennary structure. Hep G2 cells contained a high level of
      GnT-V, which catalyzes the formation of a tri'-antennary structure, and in fact a
      substantial percentage of the AFP sugar chains in these cells had the tri'
      antennary structure. alpha 1-6FT was also high, and fucosylated tri' structures
      were detected, which suggests that high activities of transferases affect the AFP
      sugar chains. In HuH-6 cells, GnT-III, which catalyzes the formation of bisecting
      GlcNAc, was elevated. Correspondingly, a fucosylated, bisected biantennary
      structure was found as a major sugar chain. In the HuH-7 cell line, the contents
      of bisecting GlcNAc and tri' structure were low and neither GnT-III nor GnT-V was
      elevated. These data indicate that the sugar structures of AFP in these cell
      lines correlate well with the activities of alpha 1-6 FT, GnT-III and GnT-V.

PMID- 1373707
TI  - Ultrastructural changes in acquired perforating dermatosis.
AB  - We performed ultrastructural studies of skin lesions in seven adults with
      acquired perforating dermatosis. Three of the patients had diabetes mellitus and
      two were undergoing hemodialysis. Lesions in an early stage showed exocytosis of
      inflammatory cells and alteration of elastic fibers. Lesions in an intermediate
      stage featured discontinuities of the basement membrane and aggregates of
      electron-dense material lateral to the perforated focus, together with dermal
      edema, scattered macrophages, and densely aggregated collagen fibers that focally
      filled the papillary dermis. Later-stage lesions showed fibroblasts in the dermis
      and degenerated elastic fibers within transepidermal channels. In most cases
      there was a single large epidermal channel lined by flattened epithelial cells,
      and containing a variety of cellular and extracellular materials. Small
      "secondary" channels without abnormal keratinization were also observed within
      the epidermis. The findings suggest that altered keratinization is limited to the
      immediate vicinity of well-formed transepidermal channels, and that exocytosis of
      inflammatory cells and alterations of elastica are early and possibly key changes
      in lesion development. The unexpected discovery of hair fragments in one case
      suggests that curled hairs may play a role in the pathogenesis of some cases of
      acquired perforating dermatosis.

PMID- 1373708
TI  - Substance P provokes cutaneous erythema and edema through a histamine-independent
      pathway.
AB  - Substance P is a neuropeptide (contained in/and released from the A delta and C
      nerve fibers of the skin), which provokes erythema, edema, and pruritus after
      intradermal injection. Local pretreatment with capsaicin produces decreased
      substance P-dependent erythema, with edema similar to that observed before
      pretreatment with capsaicin. We injected histamine and in a parallel experiment,
      substance P in five volunteers before and after local treatment with capsaicin,
      with 48/80, after 5 days of hydroxyzine. The injection of SP provoked erythema
      centered by a wheal. After treatment with 48/80, SP provoked increased erythema
      and a wheal. After hydroxyzine treatment, the injection of histamine produced no
      erythema or edema in four of the five subjects, while SP provoked erythema in all
      five subjects and edema similar to that observed before treatment with
      hydroxyzine. These data support the hypothesis that substance P provokes erythema
      and edema both with histamine-dependent and histamine-independent pathways.

PMID- 1373709
TI  - Unusual prostatic mass in a dog.
AB  - Marginal surgical resection and castration were successfully used to treat a dog
      with a large benign mass involving only the left lobe of the prostate. Pathologic
      findings were compatible with unusual nodular hyperplasia or adenoma, with smooth
      muscle proliferation. Although the definitive diagnosis remains controversial,
      the mass was termed nodular hyperplasia because of histologic and clinical
      similarities to the disease in human beings.

PMID- 1373710
TI  - Bactericidal activities of lysozyme and aprotinin against gram-negative and gram
      positive bacteria related to their basic character.
AB  - Bactericidal properties of aprotinin, a proteinase inhibitor and possibly a
      defence molecule in bovine species, and of chicken egg white lysozyme, known as
      muramidase, were investigated. Incubation of various bacteria in the presence of
      either aprotinin or lysozyme showed that both proteins killed Gram-positive as
      well as Gram-negative bacteria without addition of complement or EDTA.
      Denaturation of the two proteins by dithiothreitol did not lead to loss of their
      bactericidal potency. Electron microscopic examination of Escherichia coli
      incubated either with lysozyme or aprotinin revealed that the bacterial
      cytoplasms gradually disintegrated. Both aprotinin and lysozyme were demonstrated
      within the affected cytoplasm by immunogold labelling. The results suggest that
      the bactericidal potency of lysozyme is not only due to muramidase activity but
      also to its cationic and hydrophobic properties. The bactericidal activity of
      aprotinin is probably also related to both these properties rather than to its
      activity as proteinase inhibitor.

PMID- 1373711
TI  - Tracheal smooth muscle responses to substance P and neurokinin A in the piglet.
AB  - The tachykinins substance P (SP) and neurokinin A (NKA) have been shown to induce
      airway smooth muscle contraction in mature animals, and the enzyme neutral
      endopeptidase (NEP) modulates this effect. We evaluated maturation of SP- and NKA
      induced tracheal smooth muscle contraction and modulation of their effects by NEP
      in anesthetized, paralyzed, and artificially ventilated piglets less than 4 days,
      2-3 wk, and 10 wk of age. Tracheal smooth muscle tension was measured in vivo
      from an open tracheal segment by use of a force transducer. Intravenous SP caused
      a dose-dependent increase in tracheal tension in all three age groups; however,
      the response in less than 4-day-old piglets was significantly weaker than in 2-
      to 3- and 10-wk-old piglets. NKA caused a dose-dependent increase in tracheal
      tension only in 2- to 3- and 10-wk-old piglets. The response of tracheal tension
      to NKA was weaker than the response to SP in all age groups. Atropine (2 mg/kg)
      significantly diminished the responses of tracheal tension to SP and NKA,
      indicating a cholinergic contribution to these responses at all ages. Intravenous
      thiorphan, a known NEP inhibitor, potentiated the effects of SP only in 2- to 3-
      and 10-wk-old piglets and did not affect the response of tracheal tension to NKA
      at any age. Biochemical analyses demonstrated a significant increase in tracheal
      NEP activity in comparably aged piglets over the first 10 wk of life.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1373712
TI  - Peptide mediator effects on bronchial blood velocity and lung resistance in
      conscious sheep.
AB  - Peptide mediators or neuropeptides released from sensory nerves may induce
      inflammatory effects in airways, but their effects on airway blood velocity and
      lung resistance have not been previously studied simultaneously in awake animals.
      Nine adult sheep were chronically prepared for continuous measurement of blood
      flow velocity to the distal trachea and bronchi by surgical implantation of a 20
      MHz pulsed Doppler flow probe on the common bronchial branch of the
      bronchoesophageal artery. Awake restrained animals were intubated and connected
      to a pneumotachograph to measure resistance to airflow across the lung (RL).
      Doubling doses of bradykinin (BK, 0.02-1.51 nmol/kg), calcitonin gene-related
      peptide (CGRP, 0.004-0.26 nmol/kg), or substance P (SP, 0.02-1.19 nmol/kg) were
      injected as a bolus into the right atrium while mean arterial pressure (MAP),
      bronchial blood velocity (Vbr), and RL were measured. BK at 0.76 nmol/kg caused a
      transient dose-related increase in Vbr from a baseline of 19.3 +/- 2.5 to 41.4 +/
      4.1 (SE) cm/s (P less than 0.05) despite a decrease in MAP from 118 +/- 6 to 80
      +/- 6 mmHg. CGRP at 0.26 nmol/kg caused a transient dose-related increase in Vbr
      from 16.8 +/- 2.7 to 25.3 +/- 4.7 cm/s (P less than 0.05) despite a decrease in
      MAP from 113 +/- 5 to 87 +/- 8 mmHg. Neither BK nor CGRP affected RL. SP at 1.19
      nmol/kg transiently increased Vbr from 18.3 +/- 2.3 to 45.1 +/- 8.3 cm/s (P less
      than 0.05), MAP from 138 +/- 9 to 162 +/- 15 mmHg, and RL from 4.5 +/- 1.0 to
      106.6 +/- 62.1 cmH2O.l-1.s.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373713
TI  - Aerosolized neutral endopeptidase reverses ozone-induced airway hyperreactivity
      to substance P.
AB  - We investigated the effects of ozone exposure (3.0 ppm, 2 h) on airway neutral
      endopeptidase (NEP) activity and bronchial reactivity to substance P in guinea
      pigs. Reactivity after ozone or air exposure was determined by measuring specific
      airway resistance in intact unanesthetized spontaneously breathing animals in
      response to increasing doses of intravenous substance P boluses. The effective
      dose of substance P (in micrograms) that produced a doubling of baseline specific
      airway resistance (ED200SP) was determined by interpolation of cumulative
      substance P dose-response curves. NEP activity was measured in tracheal
      homogenates made from each animal of other groups exposed to either ozone or room
      air. By reverse-phase high-pressure liquid chromatography, this activity was
      characterized by the phosphoramidon-inhibitable cleavage of alanine-p
      nitroaniline from succinyl-(Ala)3-p-nitroaniline in the presence of 100 microM
      amastatin. Mean values of the changes in log ED200SP were 0.27 +/- 0.07 (SE) for
      the ozone-exposed group and 0.08 +/- 0.04 for the air-exposed group. We found
      that phosphoramidon significantly increased substance P reactivity in the air
      exposed animals (P less than 0.01), but it had no effect in the ozone-exposed
      group. This finding was associated with a significant reduction in tracheal
      homogenate NEP activity of ozone-exposed animals compared with controls: mean
      values were 18.1 +/- 1.9 nmol.min-1.mg protein-1 for the ozone-exposed group and
      25.1 +/- 2.4 nmol.min-1.mg protein-1 for air-exposed animals (P less than 0.05).
      Inhalation of an aerosolized NEP preparation, partially purified from guinea pig
      kidney, reversed the substance P hyperreactivity produced by ozone
      exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373714
TI  - Influence of flow on pulmonary vascular surface area inferred from blue dextran
      efflux data.
AB  - Blue dextran (BD), which binds to proteins on the pulmonary endothelial surface
      and to plasma albumin, was used in isolated perfused dog lung lobe experiments to
      address the question: do changes in perfusate flow rate cause changes in perfused
      vascular surface area? When BD was added to a protein-free perfusate under zone 3
      conditions at a high flow rate (15.8 +/- 0.7 ml/s), it was adsorbed by the
      endothelial surface. Then by changing the perfusate entering the lobe to an
      albumin-containing perfusate, the BD was eluted from the perfused surface by
      competitive binding to the perfusate albumin. The amount of BD eluted was
      measured in three experiments. In experiment 1, elution of the BD by the
      perfusate albumin was initiated after a balloon had been inflated within the
      lobar arterial tree to occlude a portion of the lobar vascular bed containing BD.
      Then the balloon was deflated, permitting albumin perfusate to perfuse the
      previously occluded part of the lobe. In experiment 2, BD elution began at a flow
      rate of 3 +/- 0.1 ml/s under zone 3 conditions and continued after the high-flow
      zone 3 conditions were reestablished. In experiment 3, the BD elution began at a
      flow rate of 4.2 +/- 0.7 ml/s under zone 2 conditions and continued after the
      high-flow zone 3 conditions were reestablished. Balloon inflation reduced the
      amount of BD recovered by 43%, demonstrating that a decrease in perfused vascular
      surface area could decrease BD recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373715
TI  - Gadolinium-DOTA enhanced MR imaging of prostatic lesions. Preliminary results on
      14 cases.
AB  - Fourteen patients with prostatic carcinoma, benign prostatic hyperplasia, or
      chronic granulomatous prostatitis underwent gadolinium-DOTA enhanced magnetic
      resonance imaging of the prostate. Gadolinium-DOTA was administered intravenously
      in a dosage of 0.1 mmol/kg body weight. All studies were performed on a
      superconductive 1.5-T system. As compared to noncontrast T1- and T2-weighted
      images, Gd-DOTA enhanced T1-weighted images were useful in distinguishing
      malignant tumor from granulomatous prostatitis in one case, but were
      uncontributive to the differentiation between carcinoma and benign prostatic
      hyperplasia.

PMID- 1373716
TI  - Acquisition of apparently intact and unmodified lipopolysaccharides from
      Escherichia coli by Bdellovibrio bacteriovorus.
AB  - The ability of Bdellovibrio bacteriovorus to relocalize the OmpF major outer
      membrane porins from its Escherichia coli prey to its own outer membranes is
      diminished in prey expressing smooth lipopolysaccharide (S-LPS). Since porins
      exist in the membrane complexed with LPS, we examined the LPS associated with
      relocalized porin to determine whether it had been acquired intact, mixed or
      replaced with Bdellovibrio LPS, or derivatized by the bdellovibrios. The
      relocalized trimers were found associated with the same LPS originally bound to
      them in the E. coli. The bulk-phase LPS from bdellovibrios grown on various
      chemotypes of rough prey was analyzed by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis to determine whether more than the trimer-bound LPS was
      acquired by the bdellovibrios. This analysis revealed bands of Bdellovibrio LPS
      matching the LPS chemotype of the prey. One or two other bands were identical in
      migration to the LPS of prey-independent mutants of B. bacteriovorus and
      represented bdellovibrio-synthesized LPS. The LPS of bdellovibrios grown on prey
      with radiolabeled lipid A showed radioactivity only in gel band positions
      identical with those of the prey's LPS. The amount of this prey-derived LPS was
      shown by enzyme-linked immunosorbent assay to reach a constant value during the
      purification of the bdellovibrios, and it represented approximately 25% of the
      total Bdellovibrio LPS. Immunoelectron microscopy confirmed the presence of prey
      derived LPS on the cell surface of bdellovibrios, and no evidence could be found
      for bdellovibrio-induced modifications of the relocalized prey LPS.

PMID- 1373717
TI  - A comparative genetic study of serologically distinct Haemophilus influenzae type
      1 immunoglobulin A1 proteases.
AB  - The bacterial immunoglobulin A1 (IgA1) proteases are putative virulence factors
      secreted by a number of human pathogens capable of penetrating the mucosal
      barrier. Among Haemophilus influenzae strains, the IgA1 protease is found in
      several allelic forms with different serological neutralizing properties. A
      comparison of the primary structures of four serologically distinct H. influenzae
      IgA1 proteases suggests that this variation is caused by epitopes of the
      discontinuous conformational type. Analysis of the homologies among the four iga
      genes indicates that the variation results from transformation and subsequent
      homologous recombination in the iga gene region among H. influenzae strains. We
      find evidence for gene rearrangements, including transpositions in the iga gene
      region encoding the secretory part of the IgA1 preprotease. The amino acid
      sequence of the C terminus of the preprotease (the beta-core), which is assumed
      to be involved in secretion of the protease by forming a pore in the outer
      membrane, is highly conserved. In contrast to conserved areas in the protease
      domain, the nucleotide sequence encoding the beta-core showed a striking paucity
      of synonymous site variation.

PMID- 1373718
TI  - Tracking genetically engineered bacteria: monoclonal antibodies against surface
      determinants of the soil bacterium Pseudomonas putida 2440.
AB  - Assessment of potential risks involved in the release of genetically engineered
      microorganisms is facilitated by the availability of monoclonal antibodies
      (MAbs), a tool potentially able to monitor specific organisms. We raised a bank
      of MAbs against the soil bacterium Pseudomonas putida 2440, which is a host for
      modified TOL plasmids and other recombinant plasmids. Three MAbs, 7.3B, 7.4D, and
      7.5D, were highly specific and recognized only P. putida bacteria. Furthermore,
      we developed a semiquantitative dot blot assay that allowed us to detect as few
      as 100 cells per spot. A 40-kDa cell surface protein was the target for MAbs 7.4D
      and 7.5D. Detection of the cell antigen depended on the bacterial growth phase
      and culture medium. The O antigen of lipopolysaccharide seems to be the target
      for MAb 7.3B, and its in vivo detection was independent of the bacterial growth
      phase and culture medium. MAb 7.3B was used successfully to track P. putida
      (pWW0) released in unsterile lake mesocosms.

PMID- 1373719
TI  - Inducibility of protein-reactive antibodies by peptide immunization: comparison
      of three epitope peptides of hen egg-white lysozyme.
AB  - Three epitope peptides of hen egg-white lysozyme (HEL) were tested for ability to
      induce antibodies reactive with native HEL. Each peptide was coupled to bovine
      gamma-globulin (B gamma G) and 4 rabbits were immunized with each peptide-B gamma
      G conjugate in complete Freund's adjuvant. The mean association constants (K0s)
      of HEL-reactive antibodies (HEL-R-Abs) from each immunizing group to [3H]acetyl
      HEL or to [3H]acetyl-peptide were measured in solution by a double antibody
      method. Only peptide loop I.II (sequences 57-107 containing Cys64-Cys80 and Cys76
      Cys94) induced high-affinity antibodies to HEL (K0 = 2.5 x 10(6)-2.3 x 10(7) M-1)
      among the three epitope peptides tested. The association constants of antipeptide
      loop I.II to [3H]acetyl peptide loop I.II were always one to two orders of
      magnitude higher than those to HEL. In addition, 50 to 80% of the anti-peptide
      loop I.II antibodies were reactive with native HEL. The specificity of anti
      peptide loop I.II was directed to a conformational feature of the peptide rather
      than to native HEL and reactivity of the antibody to HEL was interpreted as a
      kind of cross-reaction. The HEL-R-Abs from anti-Ploop I.II antisera also
      manifested neutralizing activities against the enzymic activity of HEL when
      Micrococcus luteus was used as the substrate.

PMID- 1373720
TI  - Proton dependence of the partial reactions of the sodium-proton exchanger in
      renal brush border membranes.
AB  - The pre-steady state time dependence of Na+ accumulation by the Na(+)-H+
      exchanger in renal brush border membrane vesicles was investigated at 0 degree C
      by a manual mixing technique using amiloride to quench the reaction. Dilution of
      acid-loaded (pHi 5.7) vesicles into an alkaline medium (pHo 7.7) containing 1 mM
      22Na+ produced a time course of amiloride-sensitive Na+ uptake that consisted of
      three distinct phases: 1) a lag, 2) a monoexponential "burst," and 3) a linear or
      steady state phase. Experiments testing for the presence of 22Na+ backflux,
      residual Na+ binding to the membrane, and hysteresis were negative, lending
      support to the hypothesis that the burst phase corresponds to Na+ translocation
      during the initial turnover of Na(+)-H+ exchanger. Lowering the internal pH
      increased the amount of na+ uptake in each of the phases without affecting the
      apparent burst rate, whereas lowering the external pH inhibited Na+ uptake while
      increasing the duration of the lag phase. The pattern of inhibition produced by
      external H+ was of the simple competitive type, indicating that Na+ and H+ share
      a common binding site. Steady state Na+ uptake showed a sigmoidal dependence on
      internal pH (Hill coefficient = 1.67), consistent with the presence of an
      internal allosteric H+ activation site. Alkaline loading conditions (pHi 7.7),
      which favor desaturation of the internal H+ binding sites, completely abolished
      Na+ uptake in the steady state. In contrast, Na+ accumulation during the burst
      phase was reduced to 25% of an acid-loaded (pHi 5.7) control. The persistence of
      the burst phase and the disappearance of steady state Na+ uptake under alkaline
      loading conditions suggest that recycling of the H(+)-loaded exchanger is a late
      event in the transport cycle that follows Na+ translocation (ping-pong mechanism)
      and controls the steady state rate of Na+ accumulation. Activation of the
      recycling step involves sequential binding of H+ to the allosteric and transport
      sites, thus accounting for the cooperative dependence of steady state Na+ uptake
      on the internal [H+].

PMID- 1373721
TI  - Cell attachment controls fibronectin and alpha 5 beta 1 integrin levels in
      fibroblasts. Implications for anchorage-dependent and -independent growth.
AB  - We have examined the effect of cell attachment on fibronectin and alpha 5 beta 1
      integrin levels in three distinct anchorage-dependent fibroblast cell lines.
      Analysis of long-term biosynthetically labeled proteins from parallel cultures of
      adherent and nonadherent cells showed that the steady-state level of
      extracellular fibronectin is decreased upon loss of attachment. Pulse labeling
      studies and Northern blot analyses showed that the decrease occurs post
      synthetically. A combined approach of surface radioiodination and biosynthetic
      labeling also demonstrated a selective post-synthetic decrease in cell-surface
      expression of the alpha 5 beta 1 integrin upon loss of cell attachment. Overall,
      we estimate that extracellular fibronectin and cell surface alpha 5 beta 1
      integrin levels are reduced 5-7-fold in NIH-3T3, 15-20-fold in AKR-2B, and 50
      fold in NRK fibroblasts. Finally, we find decreased total (serum- and cell
      derived) fibronectin bound to the surface of nonadherent cells consistent with
      the reduced expression of alpha 5 beta 1 integrin. These results demonstrate a
      systematic down-regulation of fibronectin and its major receptor upon loss of
      attachment and suggest a potential mechanism involved in maintenance of the
      anchorage-dependent phenotype.

PMID- 1373722
TI  - Regulation of chlorophyll apoprotein expression and accumulation. Requirements
      for carotenoids and chlorophyll.
AB  - Chlorophyll apoprotein accumulation and expression were examined in mutants of
      Chlamydomonas reinhardtii blocked at specific steps of carotenoid or chlorophyll
      synthesis. In the absence of carotenoids: 1) apoproteins of the core and light
      harvesting complexes of photosystem I (CCI and LHCI, respectively) and
      photosystem II (CCII and LHCII, respectively) do not accumulate; 2) mRNAs for the
      CCI, CCII, and LHCII apoproteins accumulate to normal levels; and 3) synthesis of
      the chlorophyll apoproteins is differentially affected, or in some cases, not
      affected. In the absence of chlorophylls: 1) the apoproteins fail to accumulate;
      2) mRNA levels for CCI and CCII apoproteins are relatively unchanged; 3) levels
      of LHCII apoprotein mRNA, but not rates of LHCII mRNA synthesis, are reduced in a
      light-dependent chlorophyll-synthesis mutant (ya12); and 4) synthesis of
      chlorophyll apoproteins is differentially affected or not affected in the case of
      several chloroplast-encoded apoproteins. These results demonstrate a direct role
      for carotenoids as well as chlorophylls in the stabilization of certain
      chlorophyll apoproteins and, for others, possibly in their translation. The data
      also indicate a role for chlorophyll synthesis in the stability of LHCII mRNA.

PMID- 1373723
TI  - Characterization of interleukin-11 receptor and protein tyrosine phosphorylation
      induced by interleukin-11 in mouse 3T3-L1 cells.
AB  - In this study, we have characterized the biochemical nature of interleukin (IL)
      11 receptors (IL-11R) and determined the possible signal transduction pathways
      mediated by IL-11 in 3T3-L1 mouse preadipocytes. The results show that IL-11
      strongly inhibited lipoprotein lipase activity and adipogenesis in 3T3-L1 cells,
      and the suppression of lipoprotein lipase activity by IL-11 was controlled at the
      post-transcriptional level. The ability of IL-11 to inhibit lipoprotein lipase
      activity and adipogenesis therefore reflected the expression of functional IL-11R
      on the cell surface. Scatchard plot analysis according to specific binding data
      revealed the existence of a single class of high affinity IL-11R with a Kd of
      3.49 x 10(-10) M and a receptor density of 5140 sites/cell on 3T3-L1 cells.
      Affinity cross-linking studies with 125I-IL-11 indicated that IL-11R consists of
      a single polypeptide chain of 151 kDa in size. Furthermore, we have studied the
      role of protein tyrosine phosphorylation in the IL-11R-linked signal transduction
      pathways. The results show that IL-11R ligation rapidly and transiently
      stimulated tyrosine phosphorylation of 152-, 94-, 47-, and 44-kDa proteins. This
      effect is specific for IL-11 since neutralizing antibody to IL-11 abrogated IL-11
      induced tyrosine phosphorylation, and other cytokines such as IL-6 and IL-1 alpha
      did not change the tyrosine phosphorylation pattern in 3T3-L1 cells. These
      results suggest that IL-11R is closely linked to a functional protein-tyrosine
      kinase pathway, and tyrosine phosphorylation may be a key step in the initiation
      of the IL-11R-mediated transmembrane signaling.

PMID- 1373724
TI  - Studies on the structure and binding properties of the cysteine-rich domain of
      rat low affinity nerve growth factor receptor (p75NGFR).
AB  - The binding domain of p75NGFR contains four "repeats" of a 6-cysteine pattern. To
      test whether these repeats have any structural or functional independence, each
      repeat has been separately deleted. In each case, deletion led to the loss of
      most nerve growth factor (NGF) binding activity. The epitopes of two monoclonal
      antibodies, MC192 and 271c, could be distinguished, however. Repeat IV was found
      to be unnecessary for binding MC192, whereas Repeat I was not required for
      binding 217c. This suggests that either terminal repeat can be removed without
      loss of native-like structure in the remaining repeats. Trp155 in the fourth
      repeat forms an essential part of the 217c epitope but is not required for either
      MC192 or NGF binding. Deletion of the linker region between the membrane-spanning
      domain and the cysteine-rich domain does not affect the binding of NGF or MC192,
      and has only a slight, if any, effect on 217c binding. Cyclic permutation of the
      four repeats failed to yield protein capable of binding NGF or MC192.

PMID- 1373725
TI  - Adhesion to vascular cell adhesion molecule 1 and fibronectin. Comparison of
      alpha 4 beta 1 (VLA-4) and alpha 4 beta 7 on the human B cell line JY.
AB  - Most mononuclear leukocytes and cell lines express the integrin alpha 4 beta 1
      (VLA-4) heterodimer. In this study we have used Northern blotting and
      immunoprecipitation experiments to demonstrate that a B lymphoblastoid cell line
      (JY) expressed the integrin beta 7 subunit in association with alpha 4. These
      alpha 4 beta 7-positive JY cells bound poorly or not at all to VLA-4 ligands
      (soluble form of vascular cell adhesion molecule 1 (sVCAM-1) and the CS1 region
      of fibronectin). In contrast, a beta 1-positive variant of JY cells (selected to
      express a mixture of alpha 4 beta 1 and alpha 4 beta 7) bound avidly to VLA-4
      ligands, and this binding was completely inhibitable by anti-alpha 4 and anti
      beta 1 monoclonal antibodies. Thus, beta 1 expression appears to be a critically
      important component of VLA-4-mediated binding to its ligands. After either JY or
      JY-beta 1 cells were stimulated for 15 min with the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate, the majority of adhesion to VCAM or fibronectin
      remained alpha 4- and beta 1-dependent, but a low amount of adhesion to sVCAM-1
      or fibronectin became alpha 4-dependent, beta 1-independent, thus suggesting a
      role for alpha 4 beta 7. In summary, we have found (i) that alpha 4 beta 7 makes
      little or no contribution to fibronectin or VCAM-1 binding on unstimulated JY
      cells, (ii) that alpha 4 beta 7 perhaps makes a minor contribution to ligand
      binding on 12-O-tetradecanoyl-phorbol-13-acetate-stimulated cells, and (iii) that
      alpha 4 beta 1 is the functionally dominant VCAM-1 and fibronectin receptor even
      when expressed in relatively low amounts compared to alpha 4 beta 7.

PMID- 1373726
TI  - Thermodynamics of oligosaccharide binding to a monoclonal antibody specific for a
      Salmonella O-antigen point to hydrophobic interactions in the binding site.
AB  - The thermodynamic characteristics of oligosaccharide binding to an antibody
      binding site that is dominated by aromatic amino acids suggest that the
      hydrophobic effect contributes substantially to complex formation as well as
      hydrogen bonding and van der Waals interactions. A detailed titration
      microcalorimetric study on the temperature dependence of the binding of a
      trisaccharide, representing the epitope of a Salmonella O-antigen, showed that
      its maximum binding to the monoclonal antibody Se155-4 occurs just below room
      temperature and both enthalpy and entropy changes are strongly dependent on
      temperature in a mutually compensating manner. The heat capacity change also
      shows an unusually strong temperature dependence being large and negative above
      room temperature and positive below. van't Hoff analysis of the temperature
      dependence of the binding constant yielded a biphasic curve with two apparent
      intrinsic enthalpy estimations (approximately -100 kJ mol-1 above 18 degrees C
      and approximately +100 kJ mol-1 below), each very different from the
      calorimetrically determined enthalpies (ranging from about -60 kJ mol-1 to -20 kJ
      mol-1). This was interpreted as being due to large enthalpy contributions from
      concomitant reactions, most notably changes in solvation. Linear plots, -delta H0
      versus -T delta S0, observed for temperature-dependent measurements mirror the
      behavior seen for a series of functional group replacements, suggesting that the
      molecular and physical origin of these phenomena are closely related and linked
      to the role of water in complex formation. The thermodynamic results are compared
      to the mode of binding determined from a 2.05-A resolution structure of the Fab
      oligosaccharide complex, and with literature data for the heat capacities of
      sugars in aqueous solution and for the thermodynamics of carbohydrate binding to
      transport proteins and lectins.

PMID- 1373727
TI  - Contribution of the N-linked carbohydrate of erythrocyte antigen CD59 to its
      complement-inhibitory activity.
AB  - The contribution of N-linked carbohydrate to the complement-inhibitory function
      of the human erythrocyte membrane glycoprotein, CD59, was investigated. Amino
      acid sequence analysis of tryptic peptides labeled with [3H]borohydride revealed
      an N-linked carbohydrate moiety at the Asn18 residue. No O-linked carbohydrate
      was detected, as judged by the failure of asialo-CD59 to bind peanut agglutinin
      and by its resistance to digestion by O-glycanase. The apparent molecular mass of
      CD59 was reduced from 18-20 to 14 kDa upon complete digestion with N-glycanase,
      with no detectable proteolysis. N-glycanase digestion of CD59 was associated with
      an 88 +/- 4% loss of the complement-inhibitory activity of the protein, as
      assessed by its capacity to protect chicken erythrocytes from lysis by the human
      C5b-9 proteins. By contrast, no change in function was observed after digestion
      of CD59 with neuraminidase, under conditions that removed greater than 60% of
      [3H]sialic acid residues. Despite loss of functional activity after N-glycanase
      digestion, we detected no change in the capacity of the deglycosylated CD59 to
      incorporate into erythrocyte membranes or to bind specifically and with species
      selectivity to the C8 and C9 components of the membrane attack complex. In order
      to alter the branched-chain structure of the N-linked carbohydrate of CD59
      without enzymatic digestion, Chinese hamster ovary (CHO) cells transfected with
      cDNA for human CD59 were grown in the alpha-mannosidase inhibitor, 1
      deoxymannojirimycin, resulting in conversion of approximately 70% of the membrane
      glycoprotein to a high mannose. When grown in the presence of 1
      deoxymannojirimycin, the C5b-9-inhibitory activity of CD59 expressed on the
      surface of the transfected CHO cells was reduced by an amount comparable to that
      observed for the N-glycanase digested protein. Taken together, these data suggest
      that normal glycosylation of Asn18 in CD59 is required for the normal expression
      of its complement-inhibitory activity on membrane surfaces, although these N
      linked sugar residues do not contribute to CD59's affinity for the C8 and C9
      components of the C5b-9 complex.

PMID- 1373728
TI  - Antibody against a cystic fibrosis transmembrane conductance regulator-derived
      synthetic peptide inhibits anion currents in human colonic cell line T84.
AB  - The cystic fibrosis (CF) phenotype is characterized by a regulatory defect in Cl-
      permeability in epithelia. A gene (250,000 base pairs) that is associated with
      this autosomal genetic disorder has been identified. To determine the cellular
      function of the recently cloned gene product, the cystic fibrosis transmembrane
      conductance regulator (CFTR), we have produced antibody against a synthetic
      peptide deduced from the CFTR cDNA sequence corresponding to positions 505-511.
      This site includes phenylalanine 508, the deletion of which is the most commonly
      expressed mutation in CF. We sought to determine whether the anti-CFTR505-511
      peptide antibody could modulate the activation of the volume-sensitive, Ca(2+)
      dependent, as well as the cAMP-dependent Cl- conductances present in the Cl(-)
      secreting human colonic T84 cell line. Affinity-purified anti-CFTR505-511
      antibody was introduced into the cytoplasm of individual T84 cells and its
      function studied using the whole-cell patch-clamp technique. Although cAMP
      dependent Cl- current activation was inhibited in cells perfused with the anti
      CFTR505-511 peptide antibody, Ca(2+)-dependent anion current activation remained
      unaffected. Chloride current activation, which accompanies cellular swelling, was
      partially attenuated in anti-CFTR505-511 antibody-loaded cells as compared with
      control cells perfused with either saline or irrelevant antibody. These results
      further support a role for CFTR in anion transport in epithelial cells and
      suggest its possible involvement in a number of anion transport pathways in
      chloride secretory epithelia.

PMID- 1373729
TI  - A hybrid ribonuclease H. A novel RNA cleaving enzyme with sequence-specific
      recognition.
AB  - A hybrid enzyme which site-specifically hydrolyzes RNA was created by covalently
      linking an oligodeoxyribonucleotide to Escherichia coli ribonuclease HI, an
      enzyme which specifically cleaves RNA moiety of DNA/RNA hybrids. A cysteine
      residue was substituted for Glu135 by site-directed mutagenesis in the mutant
      enzyme, in which all 3 free cysteine residues were replaced by alanine (Kanaya,
      S., Kimura, S., Katsuda, C., and Ikehara, M. (1990) Biochem. J. 271, 59-66), and
      coupled with a maleimide group, which is attached to the 5' terminus of the
      nonadeoxyribonucleotide (5'-GTCATCTCC-3') with a flexible tether. The resulting
      hybrid enzyme, d9-C135/RNase H, cleaved the phosphodiester bond between the fifth
      and sixth residues of the complementary nonaribonucleotide, without addition of
      the oligodeoxyribonucleotide. The nonaribonucleotide is cleaved by the wild-type
      or unmodified mutant enzyme only when the complementary oligodeoxyribonucleotide
      is present. When the kinetic parameters of the hybrid enzyme for the hydrolysis
      of the nonaribonucleotide were compared with those of the unmodified mutant
      enzyme for the hydrolysis of the nonanucleotide duplex, the hybrid enzyme
      exhibited a 7- and 4-fold decreases in the Km and kcat values, respectively,
      indicating that it performs multiple turnovers and has a sufficiently high
      hydrolytic activity. Hybrid ribonucleases H with various
      oligodeoxyribonucleotides in size and sequence, therefore, might be used as
      excellent tools for structural and functional studies of RNA.

PMID- 1373730
TI  - Characterization of squid crystallin genes. Comparison with mammalian glutathione
      S-transferase genes.
AB  - Previous experiments have indicated that the crystallins of the squid lens (S
      crystallins) are evolutionarily related to glutathione S-transferases (GST) (EC
      2.5.1.18). Here we confirm by peptide sequencing that the crystallins of the lens
      of the squid Ommastrephes sloani pacificus comprise a family of GST-like
      proteins. Squid lens extracts showed 400 times less GST activity than those of
      liver using 1-chloro-2,4-dinitrobenzene as a substrate, suggesting that the
      abundant GST-like crystallins lack enzymatic activity. Four different cDNAs
      (pSL20-1, pSL18, pSL11, and pSL4) showed 20-25% similarity in homologous regions
      with mammalian GST polypeptides. pSL20-1, pSL18, and pSL4 each encode an S
      crystallin with a unique internal peptide that is unrelated to mammalian GSTs or
      any other sequence in GenBank. The S-crystallin family is encoded in a minimum of
      9-10 genes, and the exon-intron structures of at least two of these (SL20-1 and
      SL11) are similar to those of the mammalian GST genes. The SL20-1 gene has six
      exons, with the its unique internal peptide encoded precisely in exon 4; the SL11
      gene lacks a unique internal peptide and has five exons. Experiments using
      bacterial chloramphenicol acetyltransferase as a reporter gene showed that at
      least 84 and 111 base pairs of 5'-flanking sequence are needed for function of
      the SL20-1 and SL11 promoters, respectively, in a transfected rabbit lens
      epithelial cell line (N/N1003A). Within these regions each has a putative TATA
      box and an upstream AP-1 site overlapping with antioxidant responsive-like
      elements, which are regulatory elements in the rat GST Ya and quinone reductase
      genes responsive to oxidative stress.

PMID- 1373731
TI  - Cloning, functional expression, and regulation of two K+ channels in human T
      lymphocytes.
AB  - Low stringency screening of a Jurkat cDNA library with a rat brain K+ channel
      (RCK1) probe has resulted in the isolation of HLK3, a voltage-gated K+ channel.
      In Xenopus oocytes, the HLK3 clone directs the expression of a rapidly activating
      transient outward K+ current similar to the type n K+ current recorded in Jurkat
      T cells. The HLK3 gene is located on the short arm of human chromosome 1 (p13.3).
      Polymerase chain reaction was used to clone HIsK from Jurkat cDNA. The HIsK clone
      shares the same sequence with a previously described genomic clone (Murai, T.,
      Kazikuka, A., Takumi, T., Ohkubo, H., and Nakanishi, S. (1989) Biochem. Biophys.
      Res. Commun. 161, 176-181). In Xenopus oocytes, it encodes a slowly activating,
      noninactivating K+ channel which cannot be recorded in Jurkat cells by
      conventional patch-clamp techniques. Transcripts of both clones are present at a
      similar level before and after activation of purified human T lymphocytes and
      Jurkat cells, reflecting a constitutive expression of K+ channel messages. This
      finding is in good agreement with the electrophysiological results for type n K+
      current density on the same cells. HLK3 current is very sensitive to the scorpion
      toxin charybdotoxin (IC50 = 0.8 nM). HIsK current is totally insensitive to this
      toxin but is blocked by the antiarrhythmic clofilium (IC50 = 80 microM). While
      charybdotoxin has no effect on interleukin 2 mRNA induction, clofilium potently
      inhibits interleukin 2 mRNA expression upon mitogen-induced T cell activation. It
      is concluded that the HLK3 channel is not an important component of the T cell
      mitogenic response. Other targets for K+ channel blockers, such as the HIsK
      protein, could be involved in the activation process.

PMID- 1373732
TI  - Isolation and cloning of a voltage-dependent anion channel-like Mr 36,000
      polypeptide from mammalian brain.
AB  - A polypeptide of M(r) 36,000 (36 kDa) was isolated from detergent-solubilized
      membrane fractions of mammalian brain on a benzodiazepine affinity column
      utilized for the purification of the gamma-aminobutyric acid/benzodiazepine
      receptor protein, followed by preparative gel electrophoresis. Partial protein
      sequence for two fragments of the 36-kDa polypeptide allowed the isolation of
      cDNA clones from a rat hippocampal library. An open reading frame coding a
      sequence of 295 amino acid residues containing the two probe peptide sequences
      with minor differences, and a putative N-terminal signal peptide of 25 residues
      was found. Hydropathy index revealed no regions of alpha-helix suitable for
      membrane spanning, but several areas of alternating hydrophilic and hydrophobic
      residues consistent with beta-strands. The sequence of this brain protein was 24%
      identical to that of a yeast mitochondrial protein, the voltage-dependent anion
      channel (VDAC), and over 70% identical with the VDAC from human B lymphocytes.
      The gamma-aminobutyric acid type A (GABAA) receptor/36-kDa preparation purified
      on benzodiazepine affinity column has channel-forming activity in lipid bilayer
      membranes that is virtually identical to VDAC isolated from mitochondria of
      various sources, indicating that the 36-kDa protein is a new member of the VDAC
      family of proteins. An antiserum raised against the purified 36-kDa polypeptide
      was able to precipitate [3H]muscimol binding activity, indicating a tight
      association with the GABAA receptor protein in vitro and copurification on the
      benzodiazepine affinity column due to this association. Further studies are
      needed to determine whether such an association occurs in vivo.

PMID- 1373733
TI  - Distinct distribution of vimentin and cytokeratin in Xenopus oocytes and early
      embryos.
AB  - We report the identity of a major component of Triton-insoluble extracts from
      Xenopus oocytes and early embryos. In a previous paper we showed that an
      antibody, Z9, cross-reacts with two polypeptides from such extracts (Mr 56,000
      and 57,000) as well as Xenopus vimentin. Direct microsequencing of the Mr 57,000
      protein shows near identity of three tryptic fragments with regions of the
      predicted amino acid sequence of XCK1(8), a basic cytokeratin whose mRNA is known
      to be expressed in Xenopus oocytes. We have raised an antibody, CK7, against a
      fusion protein generated from this cDNA. The specificity of this antibody has
      been tested using 1- and 2-dimensional immunoblotting, which show that it is
      specific for the Mr 56,000 and 57,000 proteins, suggesting that these two
      proteins may be the products of two non-allelic XCK1(8) genes. The antibody does
      not cross-react with vimentin. We have used CK7 to follow the distribution of
      XCK1(8) throughout development by immunoblotting and immunocytochemistry. In
      larval stages, strong staining is seen in the notocord, the apical epithelia of
      the gut, the mesentery, and a few cells in the spinal cord. In oocytes and early
      embryos, two distinct intermediate filament (IF) networks can be distinguished: a
      cortical cytokeratin network, and a deeper vimentin one. In addition, the oocyte
      germ plasm stains with Z9 but not CK7. We propose that such distinct
      distributions of each IF protein reflect functional differences during early
      development.

PMID- 1373734
TI  - Direct evidence for increased continuous histamine release in the striatum of
      conscious freely moving rats produced by middle cerebral artery occlusion.
AB  - Extracellular histamine in the stratum of conscious freely moving rats collected
      by intracerebral microdialysis 1 day after implantation of a U-shaped dialysis
      probe was measured by HPLC coupled with postcolumn o-phthalaldehyde
      derivatization fluorometry. The basal fractional histamine outputs were almost
      constant from 1 to 7 h after the start of perfusion (5.9-8.4 pg/30 min).
      Depolarization by perfusion with a high K+ (100 mM)-containing medium produced a
      significant (124%) increase and neuronal blockade by perfusion with a
      tetrodotoxin (1 microM)-containing medium resulted in a 68% reduction in the
      histamine output. The histamine output was markedly reduced by intraperitoneal
      injection of alpha-fluoromethylhistidine (100 mg/kg), an irreversible inhibitor
      of histidine decarboxylase, or (R)-alpha-methylhistamine (5 mg/kg), a potent and
      specific H3-receptor agonist. After middle cerebral artery (MCA) occlusion, the
      histamine output gradually increased, and reached four times the control value 8
      h later. When rats were pretreated with metoprine (10 mg/kg), a histamine N
      methyltransferase inhibitor, there was no significant difference in the histamine
      output between the MCA-occluded and the sham-operated groups during the first 3.5
      h after the operation, but the histamine output gradually increased thereafter in
      the MCA-occluded group. In rats treated with alpha-fluoromethylhistidine, MCA
      occlusion failed to cause an increase in the histamine output. These results
      demonstrate that MCA occlusion induces a long-lasting increase in neuronal
      histamine release in the rat striatum.

PMID- 1373735
TI  - Lipids, lipoproteins, triglyceride clearance, and cytokines in human
      immunodeficiency virus infection and the acquired immunodeficiency syndrome.
AB  - Infection causes disturbances in lipid metabolism that may be mediated by
      cytokines. Therefore we studied plasma lipids, lipoproteins, triglyceride (TG)
      metabolism, and serum cytokines in three groups: patients with the acquired
      immunodeficiency syndrome (AIDS) without active secondary infection, patients
      with evidence of human immunodeficiency virus infection but without clinical AIDS
      (HIV+), and controls. Plasma TGs and FFA were increased in AIDS, while plasma
      cholesterol, high density lipoprotein (HDL) cholesterol, apolipoprotein-A-1 (Apo
      A-1), low density lipoprotein (LDL) cholesterol, and Apo-B-100 levels were
      decreased. Increased TG levels in AIDS were primarily due to increases in very
      low density lipoprotein of normal composition; in addition, LDL and HDL were TG
      enriched. In HIV+, TGs and FFA were not increased, but total cholesterol, HDL
      cholesterol, Apo-A-1, and Apo-B-100 were significantly decreased. Interferon
      alpha (IFN alpha) and C-reactive protein levels were increased in AIDS, but tumor
      necrosis factor and haptoglobin levels were not. There was a significant
      correlation between plasma TGs and IFN alpha levels (r = 0.477; P less than
      0.01), but not between TGs and tumor necrosis factor, C-reactive protein,
      haptoglobin, or P-24 antigen. In addition, there was no relationship between
      circulating IFN alpha levels and plasma cholesterol, HDL cholesterol, Apo-A-1,
      LDL cholesterol, Apo-B-100, or FFA. TG clearance time and postheparin lipase were
      significantly decreased in AIDS and HIV+. There was a strong correlation between
      serum IFN alpha levels and TG clearance time in AIDS and HIV+ (r = 0.783; P less
      than 0.001). In summary, decreases in cholesterol and cholesterol containing
      lipoproteins (including HDL) in both AIDS and HIV+ precede the appearance of
      hypertriglyceridemia and are not related to IFN alpha or TG levels. Our data
      raise the possibility that with development of AIDS, subsequent increases in IFN
      alpha may contribute to increases in plasma TG levels in part by decreasing the
      clearance of TG.

PMID- 1373736
TI  - A potential role for endothelin-1 in human placental growth: interactions with
      the insulin-like growth factor family of peptides.
AB  - Endothelin-1 (Et-1) stimulated DNA synthesis in placental fibroblasts in a dose
      dependent manner, as measured by [3H]thymidine incorporation (ED50, 0.2-0.3
      ng/mL). Insulin-like growth factor-I (IGF-I) interacted synergistically with Et-1
      to potentiate the stimulation of DNA synthesis. Additionally, Et-1 stimulated the
      turnover of phosphoinositides in a time- and concentration-dependent manner
      (ED50, 1 ng/mL), as measured by a 2- to 3-fold increase in the total accumulation
      of [3H]inositol phosphates. This was accompanied by a 2- to 3-fold rise in
      intracellular calcium, as measured by fura-2 fluorescence. IGF-I, however, had no
      potentiating effect on Et-1-stimulated phosphoinositide turnover or increase in
      cytosolic Ca2+. The ability of Et-1 to stimulate the production of IGF-II and
      IGFBPs by placental fibroblasts was then studied. Western ligand blot analysis
      using an [125I]IGF-II probe revealed the presence of six major binding proteins
      corresponding to 42, 38, 35, 32, 31, and 24 kilodaltons. Et-1 (50 ng/mL)
      stimulated all binding fractions concordantly. This was accompanied by a similar
      increase in immunoreactive IGF-II secretion, as assessed by a specific RIA. No
      increase in immunoreactive IGF-I was observed. The ability of the placenta to
      produce Et-1 was examined by Northern blot analysis. Placentae at 14 and 17 weeks
      gestation expressed small amounts Et-1 mRNA, whereas significantly higher levels
      of mRNA were expressed at term. These data suggest that the human placenta
      produces Et-1 in a developmentally regulated manner that may act via paracrine
      and/or autocrine mechanisms to regulate placental growth.

PMID- 1373737
TI  - Report on the nomenclature of the IGF binding proteins.

PMID- 1373738
TI  - Increased binding of synovial T lymphocytes from rheumatoid arthritis to
      endothelial-leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion
      molecule-1 (VCAM-1).
AB  - The infiltration of the synovial membrane (SM) by mononuclear cells, mostly T
      cells, is a typical histopathological feature associated with rheumatoid
      arthritis (RA). The entry of T lymphocytes into the SM is believed to be mediated
      by a number of molecules in the endothelium that are induced in response to a
      series of inflammatory mediators. In this study, we have investigated the
      adhesion of synovial T cells from RA patients to two endothelial ligands:
      endothelial-leukocyte adhesion molecule-1 (ELAM-1), the only selectin known to
      function as a vascular addressin for T cells, and vascular cell adhesion molecule
      1 (VCAM-1), the cellular ligand of VLA-4. Our results clearly demonstrate that
      synovial T cells isolated from both SM and synovial fluid (SF), bearing an
      activated and memory phenotype, displayed an enhanced capacity to interact with
      these two endothelial molecules as compared with T cells from peripheral blood
      (PB) either of the same RA patients or healthy donors. A further enhancement of
      VLA-4-mediated T cell binding to VCAM-1 and fibronectin could be observed when
      already in vivo-activated synovial T cells were stimulated in vitro with phorbol
      esters, suggesting the existence of several cellular affinity levels for both
      very late activation-4 (VLA-4) ligands. Moreover, both PB and synovial T cells
      from RA patients exhibited strong proliferative responses when they were cultured
      with either fibronectin or VCAM-1 in combination with submitogenic doses of anti
      CD3 mAb. This increased endothelial binding ability of synovial T lymphocytes
      together with their proliferation in response to the interaction with VCAM-1 and
      fibronectin may represent important mechanisms in the regulation of T cell
      penetration and persistence in the chronically inflamed SM of RA.

PMID- 1373739
TI  - Evidence for renal kinins as mediators of amino acid-induced hyperperfusion and
      hyperfiltration in the rat.
AB  - This study examined the role of tissue kallikrein and kinins in renal
      vasodilation produced by infusion of amino acids (AA). In rats fed a 9% protein
      diet for 2 wk, intravenous infusion of a 10% AA solution over 60-90 min reduced
      total renal vascular resistance and increased glomerular filtration rate (GFR) by
      25-40% and renal plasma flow (RPF) by 23-30% from baseline. This was associated
      with a two- to threefold increase in urinary kinin excretion rate. Acute
      treatment of rats with aprotinin, a kallikrein inhibitor, resulted in deposition
      of immunoreactive aprotinin in kallikrein-containing connecting tubule cells and
      inhibited renal kallikrein activity by 90%. A protinin pretreatment abolished the
      rise in urinary kinins and prevented significant increases in GFR and RPF in
      response to AA. In a second group of rats pretreated with a B2 kinin receptor
      antagonist, [DArg Hyp3, Thi5,8 D Phe7]bradykinin, AA infusion raised urinary
      kinins identically as in untreated controls, but GFR and RPF responses were
      absent. Aprotinin or the kinin antagonist produced no consistent change in renal
      function in rats that were not infused with AA.AA-induced increases in kinins
      were not associated with an increase in renal kallikrein activity. Notably,
      tissue active kallikrein level fell 50% in AA-infused rats. These studies provide
      evidence that kinins generated in the kidney participate in mediating renal
      vasodilation during acute infusion of AA.

PMID- 1373740
TI  - Enhancement of incisional wound healing and neovascularization in normal rats by
      thrombin and synthetic thrombin receptor-activating peptides.
AB  - To better define thrombin-receptor interactions, we synthesized human thrombin
      peptides and identified binding-domain peptides that bind thrombin receptors and
      activate mitogenic signals (Glenn, K.C., G.H. Frost, J.S. Bergmann, and D.H.
      Carney. 1988. Pept. Res. 1:65-73). Treatment of full dermal dorsal incisions with
      a single topical application of thrombin receptor-activating peptide (TRAP-508)
      or human alpha-thrombin in saline enhances 7-d incisional breaking strength in
      normal rats up to 82% or 55% over saline-treated controls, respectively. Control
      wounds require approximately 11.5 d to achieve breaking strength equivalent to
      TRAP-treated wounds at day 7. Thus, a single application of TRAP accelerates
      healing, shifting the time course forward by up to 4.5 d. Histological
      comparisons at day 7 show more type I collagen, less evidence of prolonged
      inflammation, and an increase in number and maturity of capillaries in TRAP- and
      thrombin-treated incisions. Angiograms also show 50-65% more functional
      vascularization going across thrombin- and TRAP-treated surgical incisions. Thus,
      alpha-thrombin and thrombin peptides, such as those released following injury,
      appear to initiate or enhance signals required for neovascularization and wound
      healing. The ability to accelerate normal wound healing events with synthetic
      peptides representing receptor binding domains of human thrombin may offer new
      options for management of wound healing in man.

PMID- 1373741
TI  - Definition of a discontinuous immunodominant epitope at the NH2 terminus of the
      La/SS-B ribonucleoprotein autoantigen.
AB  - High-titer IgG autoantibodies to the La/SS-B ribonucleoprotein (RNP) are a
      hallmark of patients with primary Sjogren's syndrome. Anti-La/SS-B-positive human
      sera bind to multiple epitopes on recombinant La/SS-B, although the initial
      response is against an immunodominant epitope within the first 107 NH2-terminal
      amino acids (aa). Sequence analysis has identified a striking homology between aa
      88-101 in this NH2-terminal region of La/SS-B and a feline retroviral gag
      polypeptide suggesting the anti-La/SS-B response may be initiated by cross
      reactivity with an exogenous agent. In the present study, detailed mapping of
      this NH2-terminal epitope, using recombinant La/SS-B purified from the expression
      of overlapping DNA fragments spanning aa 1-107, has shown that this
      immunodominant epitope is a complex conformational or discontinuous epitope
      dependent upon both aa 12-28 and 82-99 for expression, even though these regions
      share no homology with each other. This requirement questions the significance of
      the homology between La/SS-B and a retroviral gag polypeptide in the generation
      of the B cell response to La/SS-B and is in accord with the general concept that
      B cells recognize conformational epitopes on antigens rather than small linear
      peptide sequences. The finding also reinforces the notion that native autoantigen
      could be the initiator of the autoimmune response.

PMID- 1373742
TI  - Induction of junB expression, but not c-jun, by granulocyte colony-stimulating
      factor or macrophage colony-stimulating factor in the proliferative response of
      human myeloid leukemia cells.
AB  - The proliferative effects of granulocyte colony-stimulating factor (G-CSF) and
      macrophage colony-stimulating factor (M-CSF) on human hematopoietic cells have
      been reported, but the intranuclear mechanism of early signal response to these
      mitogenic stimuli remains unknown. Using an established human myeloid leukemia
      cell line (NKM-1) which can grow in serum-free medium in response to G-CSF or M
      CSF, we examined expressions of the jun family genes, c-jun, junB, and junD,
      which are coexpressed by various growth factors in many tissues. In parallel with
      regrowth from the G0/G1 resting state by addition of recombinant human G-CSF or M
      CSF after serum deprivation, NKM-1 cells showed the transient expression of the
      junB gene with a peak of ninefold above the basal level between 40 and 60 min. In
      contrast, c-jun expression was not stimulated by these CSFs. JunD expression was
      constitutively observed at detectable levels. Furthermore, c-fos mRNA was rapidly
      induced to a peak of 14-fold after CSF stimulation. Transcriptional run-on assays
      revealed that treatment of serum-starved NKM-1 with 50 ng/ml G-CSF or M-CSF
      increased the transcription rate of the junB gene and the c-fos gene by 1.8-fold
      and 2.9-fold, respectively, but did not induce any transcript of the c-jun gene.
      The results indicate that the expression of the junB and c-fos genes is
      activated, at least in part, at the transcriptional level in response to these
      CSFs. These findings suggest that the signal activating c-jun expression might
      not be involved in the proliferative action of G-CSF and M-CSF but junB may be
      one of important elements in early response events of the signal transduction
      system in human CSF-responsive hematopoietic cells.

PMID- 1373743
TI  - Characterization of antibodies against human N-terminal parathyroid hormone by
      epitope mapping.
AB  - Two polyclonal antisera from goat and mouse and two monoclonal antibodies against
      human parathyroid hormone (1-34) were characterised by epitope mapping.
      Hexapeptides were synthesized on polystyrene pins, the sequences of which
      overlapped and represented the entire sequence of hPTH(1-34). Binding of
      antibodies to these hexapeptides was determined and antigenic determinants thus
      characterized. At least one predominant binding sequence was detected in the
      region of hPTH(7-14).

PMID- 1373744
TI  - Non-surgical periodontal treatment: where are the limits? An SEM study.
AB  - In the present scanning electron microscopic study, the possibilities and
      limitations of non-surgical root planing were investigated. 10 single-rooted
      teeth from 4 patients with advanced periodontitis were studied. The root surfaces
      were cleaned and planed without flap reflection, using fine curettes. The teeth
      were then extracted and the root surfaces were systematically examined by
      scanning electron microscopy (SEM) for the presence of residual bacteria and
      calculus. 29 of 40 curetted root surfaces were free of residues, if they were
      reached by the curette. On the remaining 11 surfaces, only small amounts of
      plaque and minute islands of calculus were detected, primarily at the line angles
      and also in grooves and depressions in the root surfaces. Instrumentation to the
      base of the pocket was not achieved completely on 75% of the treated root
      surfaces, however. The primary reason for this was the extremely tortous pocket
      morphology on the teeth selected for study. In conclusion, it may be stated that
      during non-surgical root planing in cases of advanced periodontitis, surfaces
      that can be reached by curettes are usually free of plaque and calculus. However,
      in many cases the base of the pocket will not be reached. It is for this reason
      that deep periodontal pockets should be treated with direct vision, i.e., after
      the reflection of conservative flaps.

PMID- 1373745
TI  - Analysis of islet cell antibodies reactivity to a human islet cell line.
AB  - A human pancreatic beta cell line (HP62) was tested for reactivity with islet
      cell antibodies (ICA) as compared with previously-established methods. Using
      indirect immunofluorescence test, we found that HP62 cell line failed to react in
      a specific way with ICA from type 1 (insulin-dependent) diabetic patients since
      sera from normal controls showed a reactivity similar to that found in the
      patients. So, the usefulness of this human beta cell line as a tool of
      immunological purpose is questioned when indirect immunofluorescence procedures
      are used.

PMID- 1373746
TI  - The state of differentiation of cultured human keratinocytes determines the level
      of intercellular adhesion molecule-1 (ICAM-1) expression induced by gamma
      interferon.
AB  - Inducing the expression of ICAM-1 (CD54) on the surface of epidermal
      keratinocytes is an important step in initiating leukocyte interaction with the
      epidermis. We studied the effect of keratinocyte differentiation and of drugs
      used to treat epidermal inflammation on the induction of this important adhesion
      molecule. Cell membrane expression of ICAM-1 in cultured human keratinocytes was
      analyzed using both immunofluorescence and FACS analysis of staining with anti
      ICAM-1 monoclonal antibody and was correlated with markers of keratinocyte
      differentiation. Cell-surface ICAM-1 expression was induced by gamma interferon
      in all culture conditions, but was significantly greater (p less than 0.014) in
      cells grown in low-calcium medium ([Ca++] 0.03 mM), and correlated with increased
      staining for the basal cell keratin K5. The synthetic retinoid Etretin (Ro 10
      1670) enhanced the interferon-induced ICAM-1 expression over a wide concentration
      range (10(-8)-10(-5) M); however, this effect was only seen in the more
      differentiated cells grown in 0.15 mM and 1.0 mM calcium and not in the cells
      grown in 0.03 mM calcium. The Etretin effects on intracellular K5 staining
      paralleled those on cell-surface ICAM-1. Anti-inflammatory glucocorticoids had no
      effect on ICAM-1 expression in cultured human keratinocytes, even at suboptimal
      gamma interferon doses (5 U/ml). beta-estradiol, on the other hand, mimicked the
      Etretin effect, increasing both IFN induction of ICAM-1 expression and K5
      staining in more differentiated keratinocytes in 0.15 and 1.0 mM calcium, but not
      in those in 0.03 mM calcium. Both Etretin and beta-estradiol decreased staining
      of involucrin, a marker of terminal differentiation, supporting the proposition
      that in this experimental system these drugs suppress keratinocyte
      differentiation. The enhanced ICAM-1 induction in keratinocytes with a basal
      level of differentiation correlates with the in vivo effects of interferon on
      ICAM-1 and may be a principal determinant in the patterns of ICAM-1 seen in
      inflammatory skin diseases.

PMID- 1373747
TI  - Dermal mast cell granules bind interstitial procollagenase and collagenase.
AB  - In order to identify structures in human skin that bind collagenase, sections
      from frozen or paraffin-embedded skin were incubated with either procollagenase
      or activated collagenase. After washing, bound procollagenase or collagenase was
      detected by immunofluorescence microscopy. In normal skin, procollagenase bound
      only to isolated granular dermal cells that were identified as mast cells on the
      basis of staining with fluoresceinated avidin and pinacyanol erythrosinate. When
      mast cells were degranulated by exposure to the ionophore A23187, extracellular
      granules bound procollagenase. Of various pathologic conditions examined, the
      highest binding of procollagenase occurred in specimens of urticaria pigmentosa.
      Procollagenase bound to granular cells and to abundant granules scattered
      throughout the dermis. Binding could be abolished by pre-treatment of tissue
      sections with heparinase or by pre-incubation of procollagenase with soluble
      heparin, suggesting that heparin is the binding agent in the granules. Activated
      collagenase also bound to dermal mast cells but in addition bound strongly to the
      dermal collagen. Enzymatic activity of activated collagenase was not inhibited by
      heparin in concentrations up to 10 mg/ml. There is evidence that mast cell
      tryptase can contribute to procollagenase activation. This study further supports
      a role for mast cells in collagenolysis by demonstrating that heparin from mast
      cells binds procollagenase and possibly serves as a reservoir for procollagenase,
      which may then subsequently be activated.

PMID- 1373748
TI  - Infiltration of both T cells and neutrophils in the skin is accompanied by the
      expression of endothelial leukocyte adhesion molecule-1 (ELAM-1): an
      immunohistochemical and ultrastructural study.
AB  - Various inducible adhesion molecules on human endothelial cells like the
      endothelial leukocyte adhesion molecule-1 (ELAM-1) seem to be the basis of
      mechanisms that allow peripheral blood leukocytes to enter precisely areas of
      inflamed tissue. Because in vitro data had shown that ELAM-1 plays a central role
      in neutrophil as well as memory T-cell endothelium interactions, we analyzed in
      vivo at the light and electron microscopic level its expression in various benign
      and malignant skin diseases, which differ in the composition of the cellular
      infiltrates. The expression of ELAM-1 on endothelial cells at different
      anatomical sites could be demonstrated independently from the cell type
      (neutrophils/memory T cells) infiltrating the surrounding tissue. On the
      ultrastructural level we demonstrate that the expression of ELAM-1 is restricted
      to certain segments of post-capillary venules exhibiting distinctive morphologic
      features. The ELAM-1-positive endothelia are identical to those vessels that are
      currently described to be the preferred sites of lymphocyte trafficking in
      diseased skin.

PMID- 1373749
TI  - Anti-inflammatory effect of cyclosporin A on human skin mast cells.
AB  - We have examined the effects of cyclosporin A (CsA) and cyclosporin H (CsH),
      which bind with different affinity to cyclophilin, to evaluate the role of this
      protein in the release of preformed (histamine) and de novo synthesized
      (prostaglandin D2[PGD2]) mediators of inflammatory reactions from human skin mast
      cells (HSMC). CsA (2.4-800 nM)-inhibited (5-60%) histamine release from HSMC
      challenged with anti-IgE. CsA exerted little, if any, inhibitory effect on
      histamine release from HSMC challenged with compound A23187 and substance P,
      whereas it completely suppressed A23187-induced histamine release from human
      basophils. Inhibition of histamine release from HSMC challenged with anti-IgE was
      extremely rapid and was not abolished by washing (three times) the cells before
      anti-IgE challenge. CsA (2.4-800 nM) markedly inhibited (25-70%) the de novo
      synthesis of PGD2 from HSMC challenged with anti-IgE. CsH, which has an extremely
      low affinity for cyclophilin, had no effect on skin mast-cell mediator release.
      These data suggest that CsA is a potent anti-inflammatory agent acting on HSMC,
      presumably by interacting with cyclophilin.

PMID- 1373750
TI  - Identification of skin as a major site of prostaglandin D2 release following oral
      administration of niacin in humans.
AB  - Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce
      serum cholesterol levels induces intense flushing in humans. We have recently
      shown that the vasodilation following ingestion of niacin is due to the release
      of prostaglandin (PG) D2. However, the site from which PGD2 is released is not
      known. It has previously been shown that topical application of methylnicotinate
      causes local cutaneous erythema. Thus, we investigated whether topical
      methylnicotinate causes a release of PGD2 locally from skin and the possibility
      that skin may be a major contributor to the release of PGD2 when niacin is
      administered by mouth. Topical administration of methylnicotinate (10(-1) M) to
      the forearms of human volunteers resulted in 58- to 122-times increases in levels
      of PGD2 and 25- to 33-times increases in levels of the metabolite of PGD2, 9
      alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated
      sites. Increased levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood
      drawn simultaneously from veins in the contralateral arm, indicating that the
      PGD2 was released from the site of methylnicotinate application. The release of
      PGD2 in response to topically applied methylnicotinate occurred in a dose
      dependent manner over the concentration range of 10(-3) to 10(-1) M. The release
      of PGD2 was not accompanied by a release of histamine, suggesting that the
      release of PGD2 was not from the mast cell. Following oral ingestion of niacin,
      levels of PGD2 in superficial venous blood draining the skin were 14 to 1200
      times higher than the level in arterial blood supplying the skin of the same arm.
      This finding indicates that the skin is a major site from which PGD2 is released
      following oral ingestion of niacin. These studies thus indicate that the
      cutaneous vasodilation that occurs following oral administration of niacin is
      primarily due to a release of PGD2 from a niacin responsive cell that resides in
      the skin.

PMID- 1373751
TI  - Human T lymphotropic virus types I- and II-specific antibody-dependent cellular
      cytotoxicity: strain specificity and epitope mapping.
AB  - Antibody-dependent cellular cytotoxicity (ADCC) against human T lymphotropic
      virus (HTLV) types I and II was investigated using sera obtained from infected
      individuals or from rabbits immunized with HTLV-I or -II envelope peptides.
      Target cells included an HTLV-I-transformed cell line (C91/PL), an HTLV-II
      transformed cell line (729pH6neo), and Epstein Barr virus (EBV)-transformed B
      lymphocytes expressing HTLV-I or -II env or gag gene products after infection
      with vaccinia/HTLV recombinants. ADCC activity was directed at HTLV-I and -II
      envelope glycoproteins but not against core (gag) components. In contrast to the
      human immunodeficiency virus system, significant cross-reactivity between HTLV-I-
      and -II-directed ADCC activity was observed. Epitope mapping studies using sera
      from rabbits that had been immunized with HTLV-I or -II envelope peptides
      suggested that the critical epitopes for ADCC activity are located primarily in
      hydrophilic regions of the exterior (gp46) part of the envelope glycoprotein.

PMID- 1373752
TI  - Infectious respiratory syncytial virus (RSV) effectively inhibits the
      proliferative T cell response to inactivated RSV in vitro.
AB  - The effect of respiratory syncytial virus (RSV) on the cellular immune response
      of human mononuclear cells in vitro was examined. Inhibition by RSV of the
      lymphocyte response to phytohemagglutinin in vitro was confirmed using cells from
      human umbilical cord blood. In addition, RSV significantly inhibited both the
      proliferative and T cell colony responses of human mononuclear cells to Epstein
      Barr virus. An RSV-specific cellular immune response was induced in vitro by
      stimulation of mononuclear cells from RSV-seropositive donors with beta
      propiolactone-inactivated RSV. This RSV-specific response was significantly
      inhibited by infectious RSV itself, and the inhibition was mediated by an
      extracellular factor produced by RSV-infected mononuclear cells. A similar
      inhibition in vivo of the RSV-induced cellular immune response may contribute
      significantly to delayed recovery from primary infection and to reduced
      resistance to subsequent infections.

PMID- 1373753
TI  - Rotavirus-specific breast milk antibody in two populations and possible
      correlates of interference with rhesus rotavirus vaccine seroconversion.
AB  - Milk was collected from 56 New York and 70 Venezuelan mothers participating in
      Rhesus rotavirus (RRV) pediatric vaccine trials. Plaque reduction neutralization
      antibody (PRNA) to RRV (VP7:3, VP4:RRV) and human P rotavirus (VP7:3, VP4:P) and
      epitope-blocking antibody to one RRV VP4 and VP7 epitope were determined.
      Controlling for postpartum age, more Venezuelan milk samples had detectable RRV
      and P PRNA, RRV VP4 epitope-blocking antibody (P less than or equal to .001), and
      higher RRV and P PRNA geometric mean titers (P = .01) than New York samples.
      Using a logistic regression model, both milk and infants' serum preimmunization
      RRV PRNA titers had a negative effect on seroconversion (P = .008 and .02,
      respectively). Only 25% (2/8) infants fed milk containing greater than or equal
      to 1:160 RRV PRNA seroconverted compared with 83% (5/6) fed milk containing less
      than 1:160 RRV PRNA (P = .1). Of milk samples containing greater than or equal to
      1:160 RRV PRNA, seven (88%) of eight had greater than fourfold neutralizing
      activity against RRV versus P (P = .035), suggesting that VP4-specific milk
      antibodies may interfere with RRV seroconversion.

PMID- 1373755
TI  - Cytokeratin pattern of clinically intact and pathologically changed oral mucosa.
AB  - The various cytokeratin polypeptides in oral epithelia are expressed in
      dependence on site and formation of a stratum corneum. Certain cytokeratins occur
      permanently and others occasionally. In fibrous hyperplasia and Lichen ruber
      planus, patterns of cytokeratins did not deviate significantly from normal. In
      some but not all cases of squamous cell carcinoma and leukoplakia studied, marked
      aberrations of pattern were characterized by (i) appearance of cytokeratin No.
      19, (ii) somewhat more frequent occurrence of cytokeratins Nos. 8 and 18, (iii)
      proteolytic modifications of cytokeratins, and (iv) partial loss of a few site
      specific cytokeratins. The aberrations may be taken as additional diagnostic
      criteria for differentiation between non-aggressive and potentially aggressive
      leukoplakic lesion, even if they are not correlated with the conventional
      histological grading of dysplasia.

PMID- 1373754
TI  - Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine
      brain endothelial cells via a serum-dependent cytotoxic pathway.
AB  - An in vitro blood-brain barrier (BBB) model consisting of primary cultures of
      bovine brain microvascular endothelial cells was used to examine the effect of
      Haemophilus influenzae type b (Hib) on the BBB. Whole bacteria and purified
      lipopolysaccharide (LPS; greater than 10 ng/ml) caused marked cytotoxicity on the
      bovine brain endothelial cells. This effect could be completely blocked by
      polymyxin B. Similar cytotoxic effects were observed with a cultured bovine
      pulmonary endothelial cell line. Serum was essential for the LPS-mediated
      cytotoxic effect, and human, horse, bovine, or fetal calf serum all had similar
      effects. The serum factor was not a complement component. A monoclonal antibody
      against CD14, a receptor involved in mediating the effect of LPS in monocytes,
      completely blocked the cytotoxic effect in both brain and pulmonary endothelial
      cells. These results suggest that Hib LPS disrupts an in vitro BBB model via a
      serum- and CD14-dependent pathway and that LPS has cytotoxic effects on bovine
      endothelial cells without the involvement of monocytic cells, an effect that may
      be important in gram-negative meningitis and in endotoxic shock.

PMID- 1373756
TI  - Immunohistochemical localisation of substance P in human parotid gland.
AB  - Based on the clinical observation that pain is experienced during parotid gland
      surgery under local anaesthesia, the presence of the sensory neuropeptide
      substance P (SP) was sought. Using a polyclonal antibody, the presence of SP was
      demonstrated by an indirect immunofluorescence technique, with rat parotid gland
      and spinal cord serving as controls. SP-containing neuronal elements occurred
      around acini, blood vessels and ducts. It is suggested that some of the SP
      immunoreactive elements are the unmyelinated and thinly myelinated small diameter
      (A delta and C) fibres, which are regarded as the peripheral receptors for
      nociceptive information.

PMID- 1373757
TI  - Immunological discrimination between the human apolipoprotein E2(Arg158----Cys)
      and E3 isoforms.
AB  - A specific anti-apoE2(Arg158----Cys) monoclonal antibody was raised by means of
      immunization of mice with a variant specific synthetic peptide. The peptide
      sequences used were homologous to apolipoprotein E of human and mouse.
      Consequently, the mouse immune system was tolerant to most of the selected
      sequences. Immunization with only one of selected peptides (amino acids 154-172)
      evoked an anti-peptide and anti-native protein response. Surprisingly, this
      peptide was predicted to have a low antigenicity index, in contrast to the other
      used peptides. The variant specific anti-peptide MAb that was generated with this
      sequence, recognizes apoE2(Arg158----Cys) and not apoE3. We here describe a
      sensitive, time saving, and simple immunoblot assay to detect apoE2(Arg158---
      Cys) in human sera without prior isoelectric focusing of serum proteins.

PMID- 1373758
TI  - Human immunodeficiency virus (HIV) Tat-reactive antibodies present in normal HIV
      negative sera and depleted in HIV-positive sera. Identification of the epitope.
AB  - We have detected, in sera of normal human immunodeficiency virus (HIV)-free
      subjects, IgM antibodies reactive with the Tat protein of HIV in significant
      titers and at very high frequency, and, in HIV-positive sera, progressively lower
      titers as HIV pathogenesis ensues. Epitope analysis indicates that the Tat
      reactive antibodies of both HIV-negative and HIV-positive sera are homologous,
      suggesting, therefore, that their decline in HIV-positive sera may represent
      attrition of a host defense factor. The identified epitope displays minimal
      homology with that previously defined for another set of IgM antibodies shown to
      be present in normal sera, deficient in HIV-positive sera, and postulated to be
      natural antibodies. We propose that the Tat-reactive antibodies, as well, are a
      set of natural antibodies and that the normal humoral immune system includes a
      repertoire of antibodies, nonimmunogenic in origin, that contribute to immune
      homeostasis and, consequently, to host resistance to HIV pathogenesis.

PMID- 1373759
TI  - Induction of IgG3 secretion by interferon gamma: a model for T cell-independent
      class switching in response to T cell-independent type 2 antigens.
AB  - T cell-independent type 2 (TI-2), in contrast to T-dependent, antigens stimulate
      the production of murine IgG3. To investigate a possible role for cytokines in
      mediating the induction of this IgG subclass, we established an in vitro
      polyclonal model system for studying TI-2 antigen-mediated B cell activation by
      using dextran-conjugated anti-IgD antibody (alpha delta-dex). We demonstrate that
      interferon gamma (IFN-gamma) stimulates, and interleukin 4 inhibits, the
      expression of IgG3 by alpha delta-dexactivated cells. The production of IFN-gamma
      by non-T cells in response to bacterial products, possibly capsular
      polysaccharides, may provide an explanation underlying the ability of TI
      antigens, which are unable to directly stimulate T cell-derived cytokines to
      induce Ig isotype switching.

PMID- 1373760
TI  - Phase II trial of fludarabine phosphate in lymphoma: an effective new agent in
      low-grade lymphoma.
AB  - PURPOSE: In a phase II trial we investigated fludarabine phosphate (FAMP) as
      therapy for patients with relapsed lymphoma to determine its effectiveness and
      toxicity in this disease. PATIENTS AND METHODS: The 67 assessable patients had a
      median age of 56 years and had received a median of three chemotherapy regimens
      before treatment with FAMP. The starting dose was 25 mg/m2 administered
      intravenously over 30 minutes daily for 5 days every 3 to 4 weeks. RESULTS: High
      response rates were observed for follicular small cleaved-cell lymphoma (FSCCL)
      (62%), follicular mixed small- and large-cell lymphoma (80%), and follicular
      large-cell lymphoma (FLCL) (100%). Responses also occurred in small lymphocytic
      lymphoma (SLL) (33%), transformed lymphoma (33%), mycosis fungoides (40%), and
      Hodgkin's disease (25%). No responses were observed in other intermediate- or
      high-grade lymphomas (N = 20). Overall, there were five patients with a complete
      response, 23 patients with a partial response, and an overall response rate of
      37%. Toxicity was primarily hematologic and infectious. No significant
      gastrointestinal, hepatic, renal, or neurologic toxicity occurred. CONCLUSIONS:
      We conclude that FAMP has major activity in follicular lymphoma. Fundamental
      research is needed to understand this differential efficacy in low-grade lymphoma
      yet lack of efficacy in intermediate- and high-grade lymphoma. Clinical
      investigations should be done using FAMP in varying dose schedules and in
      combination regimens.

PMID- 1373761
TI  - FMRFamide effects on membrane properties of heart cells isolated from the leech,
      Hirudo medicinalis.
AB  - 1. The effects of the cardioactive peptide FMRFamide were tested on enzymatically
      dissociated muscle cells isolated from hearts of the leech. These cells were
      normally quiescent, with resting potentials near -60 mV. 2. Superfusion of
      FMRFamide induced a strong depolarization in isolated heart cells (e.g., greater
      than 40 mV with 10(-6) M FMRFamide). The depolarization was maintained in the
      continued presence of peptide and persisted long after its removal. Less
      frequently, FMRFamide superfusion elicited an episodic polarization rhythm. 3.
      The response of isolated heart cells to bath-applied FMRFamide showed a 1- to 2
      min latency. The latency decreased with repeated applications of FMRFamide. 4.
      The FMRFamide response was diminished by Na+ replacement but persisted with Ca2+
      channel blockade. 5. In voltage-clamped heart cells (-60 mv), superfusion of
      FMRFamide elicited a slow inward current with a transient and a sustained
      component. 6. Current-voltage (I-V) curves during FMRFamide superfusion in normal
      leech saline showed that FMRFamide also enhanced voltage-dependent outward
      currents activated at depolarized levels. 7. Under conditions in which K+
      currents were substantially blocked, the FMRFamide-dependent I-V curve was net
      inward from -90 to +50 mV. A voltage-dependent component was blocked by Co2+ and
      a linear component by Na+ replacement. 8. We conclude that FMRFamide elicits a
      persistent inward current with a Na+ component and in addition modulates both
      voltage-dependent Ca2+ and K+ currents that may contribute to the normal myogenic
      activity of leech heart muscle cells.

PMID- 1373762
TI  - Ionic currents of the lateral pyloric neuron of the stomatogastric ganglion of
      the crab.
AB  - 1. The lateral pyloric (LP) neuron is an important component of the network that
      generates the pyloric rhythm of the stomatogastric ganglion (STG) and is a direct
      target of many modulatory inputs to the STG. Our aim in this and the subsequent
      two papers is to describe the conductances present in this cell and to understand
      the role these conductances play in shaping the activity of the neuron. 2. LP
      neurons were studied in two-electrode voltage clamp (TEVC) in a saline solution
      containing tetrodotoxin (TTX) and picrotoxin (PTX) to isolate them
      pharmacologically from presynaptic inputs. 3. We identified six voltage-dependent
      ionic conductances. These include three outward currents that resemble a delayed
      rectifier current, a Ca(2+)-activated K+ current and an A-current similar to
      those seen in many other preparations. LP neurons show three inward currents, a
      fast TTX-sensitive current, a hyperpolarization-activated inward current, and a
      Ca2+ current.

PMID- 1373763
TI  - Mathematical model of an identified stomatogastric ganglion neuron.
AB  - 1. The ionic currents in the lateral pyloric (LP) cell of the stomatogastric
      ganglion (STG) described in the preceding paper of the rock crab Cancer borealis
      were fit with a set of differential equations that describe their voltage, time,
      and Ca2+ dependence. The voltage-dependent currents modeled are a delayed
      rectifier-like current, id; a Ca(2+)-activated outward current, io(Ca); a
      transient A-like current, iA; a Ca2+ current, iCa; an inwardly rectifying
      current, ih; and a fast tetrodotoxin (TTX)-sensitive Na+ current, iNa. 2. A
      single-compartment, isopotential model of the LP cell was constructed from the
      six voltage-dependent currents, a voltage-independent leak current il, a Ca2+
      buffering system, and the membrane capacitance. 3. The behavior of the model LP
      neuron was compared with that of the biological neuron by simulating
      physiological experiments carried out in both voltage-clamp and current-clamp
      modes. The model and biological neurons show similar action-potential shapes,
      durations, steady-state current-voltage (I-V) curves, and respond to injected
      current in a comparable way.

PMID- 1373764
TI  - Contribution of individual ionic currents to activity of a model stomatogastric
      ganglion neuron.
AB  - 1. The behavior of the mathematical model for the lateral pyloric (LP) neuron of
      the crustacean stomatogastric ganglion (STG) developed in the previous paper was
      further studied. 2. The action of proctolin, a neuromodulatory peptide that acts
      directly on the LP neuron, was modeled. The effect of the proctolin-activated
      current (iproc) on the model neuron mimics the effects of proctolin on the
      isolated biological LP neuron. The depolarization and increased frequency of
      firing seen when iproc is activated are associated with changes in the relative
      contributions of the delayed rectifier (id) and the Ca(2+)-activated outward
      current (io(Ca] to the repolarization phase of the action potential. 3. The
      effects of turning off the A-current (iA) in the model were compared with those
      obtained by pharmacologically blocking iA in the biological neuron. iA appears to
      regulate action-potential frequency as well as postinhibitory rebound activity.
      4. The role of iA on the rhythmic activity of the cell was studied by modifying
      several of its parameters while periodically activating a simulated synaptically
      activated conductance, isyn. 5. The effects of manipulations of the maximal
      conductances (g) for id and io(Ca) were studied. id strongly influences action
      potential frequency, whereas io(Ca) strongly influences action-potential
      duration. 6. Modifications of the maximal conductance of the inward Ca2+ current
      (iCa) were compared with the effects of blocking iCa in the real cell. 7. The
      role of the hyperpolarization-activated inward current (ih) during ongoing
      rhythmic activity was assessed by periodically activating isyn while modifying
      ih.

PMID- 1373765
TI  - Relationship between repetitive firing and afterhyperpolarizations in human
      neocortical neurons.
AB  - 1. Human neocortical neurons fire repetitively in response to long depolarizing
      current injections. The slope of the relationship between average firing
      frequency and injected current (f-I slope) was linear or bilinear in these cells.
      The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing
      episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during
      a 1-s constant-current injection (spike frequency adaptation). Also, human
      neurons exhibited habituation in response to a 1-s current stimulus repeated
      every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic
      conductances after action potentials. We studied AHPs with the use of
      intracellular recordings and pharmacological manipulations in the in vitro slice
      preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and
      2) elucidate the role that the underlying currents play in the functional
      behavior of human cortical neurons. 3. We have classified three AHPs in human
      neocortical neurons on the basis of their time courses: fast, medium, and slow.
      The amplitude of the AHPs was dependent on stimulus intensity and duration,
      number and frequency of spikes, and membrane potential. 4. The fast AHP had a
      reversal potential of -65 mV and was eliminated in extracellular Co2+,
      tetraethylammonium (TEA) or 4-aminopyridine, and intracellular TEA or CsCl. These
      manipulations also caused an increase in spike width. 5. The medium AHP had a
      reversal potential of -90 to -93 mV (22-24 mV hyperpolarized from mean resting
      potential). This AHP was reduced by Co2+, apamin, tubocurare, muscarine,
      norepinephrine (NE), and serotonin (5-HT). Pharmacological manipulations suggest
      that the medium AHP is produced in part by 1) a Ca-dependent K+ current and 2) a
      time-dependent anomalous rectifier (IH). 6. The slow AHP reversed at -83 to -87
      mV (14-18 mV hyperpolarized from mean resting potential). This AHP was diminished
      by Co2+, muscarine, NE, and 5-HT. The pharmacology of the slow AHP suggests that
      a Ca-dependent K+ current with slow kinetics contributes to this AHP. 7. The
      currents involved in the fast AHP are important in spike repolarization, control
      of interspike interval during repetitive firing, and prevention of burst firing.
      Currents underlying the medium and slow AHPs influence the interspike interval
      during repetitive firing and produce spike frequency adaptation and habituation.

PMID- 1373766
TI  - Use-dependent fade and slow recovery of long-term potentiation in superior
      cervical ganglion of the cat.
AB  - 1. In anesthetized cats under partial block of nicotinic ganglionic transmission
      by hexamethonium and in which the cervical sympathetic trunk (CST) was split into
      two bundles of approximately equal size, a 40-Hz 5-s conditioning stimulus train
      to one bundle produced prolonged potentiation of the postganglionic compound
      action potential evoked by a test stimulus to the same or to the other bundle
      [homosynaptic and heterosynaptic, respectively, long-term potentiation (LTP)].
      The LTP was detected also by recording the nictitating membrane (NM) contraction
      in response to a test preganglionic train. 2. The homosynaptic or heterosynaptic
      LTP produced by applying the conditioning 40-Hz 5-s train to one bundle was
      markedly depressed in amplitude and duration after stimulation of that bundle at
      40 Hz for 20 min, whereas the homosynaptic or heterosynaptic LTP produced by
      applying the conditioning 40-Hz 5-s train to the other bundle was unchanged. The
      latter evidence suggests that all superior cervical ganglion (SCG) synapses can
      still express LTP during the depression that follows the 40-Hz 20-min train. 3.
      In 4 h there was no appreciable recovery of LTP from the depression produced by a
      40-Hz 20-min train (n = 5). However, after 3 days (n = 3) and 5 days (n = 3), LTP
      recovered to 53 and 90% of control, respectively. 4. When colchicine was applied
      to the CST bilaterally, at a concentration sufficient to block fast axonal
      transport, and one CST only was stimulated for 20 min at 40 Hz, the LTP recorded
      4 days later was significantly smaller on the stimulated than on the
      contralateral, control, side.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373767
TI  - Pharmacokinetics of rhenium-186 after administration of rhenium-186-HEDP to
      patients with bone metastases.
AB  - The pharmacokinetics of 186Re-HEDP, a radiopharmaceutical for palliative
      treatment of metastatic bone pain, was investigated in 11 patients (17 studies)
      who suffered from metastatic breast or prostate cancer. Half-life times of 186Re
      in three blood fractions (whole blood, plasma and plasma water) were 40.1 +/-
      5.0, 41.0 +/- 6.0 and 29.5 +/- 6.4 hr, respectively. Time-dependent increase in
      plasma-protein binding was observed, probably caused by in vivo decomposition of
      186Re-HEDP. Total urinary 186Re excretion was 69% +/- 15%, of which 71% +/- 6%
      was excreted in the first 24 hr after injection. The BSI (i.e., fraction of the
      skeleton showing scintigraphic evidence of metastatic disease) closely correlated
      with the fraction of dose non-renally cleared (r = 0.98). This implies that the
      amount of radioactivity taken up by the skeleton and hence the bone marrow
      absorbed dose can be predicted from a diagnostic pre-therapy 99mTc-HDP
      scintigram. The pharmacokinetic behavior indicates that 186Re-HEDP has suitable
      properties to justify its application.

PMID- 1373768
TI  - Vascularization and endochondral bone development: changes in plasminogen
      activator activity.
AB  - Changes in plasminogen activator activity were studied during the sequential
      developmental stages of matrix-induced cartilage, bone, and bone marrow
      development. The morphological transitions were correlated with biochemical
      parameters. Morphologic evidence of vascularization of calcified hypertrophic
      cartilage was accompanied by a concomitant rise in plasminogen activator
      activity. Thereafter, a steady decline during mineralization and deposition of
      new bone was observed. Maximal plasminogen activator activity occurs at
      approximately the same time as peak activity of alkaline and acid phosphatase.
      These results imply a role for plasminogen activator during angiogenesis,
      vascular invasion, and attendant bone differentiation.

PMID- 1373769
TI  - [Evaluation of terminal care for head and neck cancer patients].
AB  - The terminal care of patients with cancer has come to involve important medical
      and social problems. We evaluated our terminal care in 52 patients with head and
      neck cancer. The results were that pain couldn't be controlled in 40% of these
      patients. In the last two weeks before death, only 28.8% of the patients could
      take food orally and only 23.1% could speak. We also assessed dyspnea, mental
      symptoms, and the management of general condition. Although it is still difficult
      to maintain Q.O.L. for head and neck cancer patients, improvement in the near
      future is essentiated.

PMID- 1373770
TI  - [Immunohistochemical studies on the guinea pig's vestibular ganglion cell--with
      reference to the distribution of substance P and neurofilament].
AB  - The immunocytochemical distribution and morphological characteristics of
      substance P and neurofilament in vestibular end organs and the vestibular
      ganglion of the guinea pig were investigated. The effect of capsaicin on
      substance P-like immunoreactivity was also evaluated in this study. Substance P
      like immunoreactivity was found in the peripheral region of vestibular end organs
      and in small or medium size vestibular ganglion cells. Approximately 85% of
      vestibular ganglion cells showed substance P-like immunoreactivity. Although
      substance P-like immunoreactivity was depleted in the nasal mucosa and trigeminal
      ganglion by capsaicin treatment, substance P distributed in the primary
      vestibular neurons was not affected. In contrast to the distribution of substance
      P, neurofilament was also found in the primary afferent neurons in the central
      regions of vestibular end organs. Neurofilament immunoreactive cells, which were
      larger in size than cells without neurofilament-like immunoreactivity comprised
      about 34% of vestibular ganglion cells. These immunocytochemical findings suggest
      that vestibular ganglion cells can be classified on the basis of size and
      immunocytochemical characteristics.

PMID- 1373771
TI  - Standardization of the Denver Developmental Screening Test for Armenian children.
AB  - To establish the cultural validity of the Denver Developmental Screening Test
      norms for Armenian children, a convenience sample of 39 children enrolled in an
      Armenian elementary school were studied. The results indicate the established
      norms are valid for children of Armenian culture. The test was first administered
      in English; items were translated into Armenian only in the case of a
      questionable initial finding. Language, cultural differences, and child rearing
      practices contributed to deviations from the norms. These differences should be
      considered when using the Denver Developmental Screening Test with ethnic groups.

PMID- 1373772
TI  - Life events, social support, and children's competence after parent and sibling
      death.
AB  - The purpose of this study was to ascertain whether children's competence after a
      parent or sibling death is related to stressful life events and the social
      support which occur around the time of a death. The sample consisted of 37
      children between the ages of 7 and 15 years old who lost a sibling or parent by
      death 1 to 4 years previously. Study variables were measured through parent
      completion of mailed questionnaires. Life events, parent support, and support by
      other people were examined in relation to children's current cognitive, social,
      physical, and behavioral competence. Stressful life events were found to be
      related differentially to the four aspects of children's competence. Neither
      parental support nor support by others was associated with any of the competence
      dimensions.

PMID- 1373773
TI  - Refined structure of the pore-forming domain of colicin A at 2.4 A resolution.
AB  - The E1 subgroup (E1, A, B, IA, IB, K and N) of anti-bacterial toxins called
      colicins is known to form voltage-dependent channels in lipid bilayers. The
      crystal structure of the pore-forming domain of colicin A from Escherichia coli
      has been refined to the diffraction limit of the crystals at 2.4 A resolution by
      means of molecular dynamics and restrained least-squares methods to a
      conventional R-factor of 0.18 for all data between 6.0 and 2.4 A resolution. The
      polypeptide chain of 204 amino acid residues consists of ten alpha-helices
      organized in a three-layer structure. The helices range in length from 9 to 23
      residues with an average length of 125 residues. The packing arrangement of the
      helices has been analysed; the packing is different from that observed in four
      helix bundle proteins. The sites of 83 water molecules have been located and
      refined. Analysis of the structure provides insights into the mechanism of
      formation of a voltage-gated channel by the protein. Although it is proposed that
      substantial tertiary structural changes occur during membrane insertion, the
      secondary structural elements remain conserved. This idea has been proposed
      recently for a number of other protein-membrane events and thus may have more
      general applicability.

PMID- 1373774
TI  - Crystal structure of alpha-dendrotoxin from the green mamba venom and its
      comparison with the structure of bovine pancreatic trypsin inhibitor.
AB  - The three-dimensional structure of alpha-dendrotoxin (alpha-DTX) from the green
      mamba (Dendroaspis angusticeps) venom has been determined crystallographically
      using the method of isomorphous replacement and refined at 2.2 A resolution using
      a restrained least-squares method. The crystallographic R-factor is 0.169 for all
      3451 measured reflections between 7.0 and 2.2 A. Although the main-chain fold of
      alpha-DTX is similar to that of homologous bovine pancreatic trypsin inhibitor
      (BPTI), there are significant differences involving segments of the polypeptide
      chain close to the "antiprotease site" of BPTI. Comparison of the structure of
      alpha-DTX with the existing models of BPTI and its complexes with trypsin and
      kallikrein reveals structural differences that explain the inability of alpha-DTX
      to inhibit trypsin and chymotrypsin.

PMID- 1373775
TI  - Kinetic roles and conformational properties of the non-native two-disulphide
      intermediates in the refolding of bovine pancreatic trypsin inhibitor.
AB  - The most productive folding pathway of reduced bovine pancreatic trypsin
      inhibitor (BPTI) proceeds through the disulphide intermediates (30-51), (30-51, 5
      14), and (30-51, 5-38); these are important kinetic intermediates in folding,
      even though the latter pair contain non-native disulphide bonds. Analogues of
      these intermediates have been prepared by protein engineering methods and their
      conformational properties examined by circular dichroism and 1H-nuclear magnetic
      resonance. The (30-51), (30-51, 5-14) and (30-51, 5-38) analogues exhibit
      comparable degrees of stable structure, which cannot include those portions of
      the polypeptide chain involving Cys5, Cys14 and Cys38. These properties are
      consistent with the roles of (30-51, 5-14) and (30-51, 5-38) in the folding
      pathway of BPTI, which demand that they exhibit a considerable degree of
      conformational flexibility in part of the molecule.

PMID- 1373776
TI  - Expression of myeloid cell phenotypes by a novel adult T-cell leukemia/lymphoma
      cell line.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) can infect a number of
      cells of different lineages in vitro, yet the immunophenotypes of most adult T
      cell leukemia/lymphomas (ATLs) are restricted to CD4+. The apparent discrepancy
      between these findings is still largely unknown. PURPOSE: We report on a unique
      case of ATL in which the leukemia cells were positive for both T-cell and myeloid
      cell antigens. To characterize these cells, we isolated cell lines from this
      patient with ATL. METHODS: The fresh leukemia cells were cultured without the
      addition of interleukin-2. Cell cloning was carried out by limiting dilution.
      RESULTS: A cell line (MU) and its clonal sublines were established. MU cells
      showed the same chromosomal abnormalities and T-cell receptor beta-chain gene
      rearrangement pattern as those of fresh leukemia cells. MU cells were exclusively
      positive for a myeloid cell marker (CD13) but not for T-cell markers, despite the
      presence of T-cell receptor gene rearrangement. CONCLUSION: The established ATL
      cell line showed both T-cell and myeloid cell characteristics, which seems to be
      the first evidence for the close association of ATL cells with both lymphoid and
      myeloid features. The cell line may provide a new insight for the targets of HTLV
      1 infection and transformation in vivo.

PMID- 1373777
TI  - Modulation of the endotoxin receptor (CD14) in septic patients.
AB  - The monocyte is a pivotal cell in septic patients that responds to endotoxin with
      release of inflammatory cytokines. Monocytes display on their surface a receptor
      (CD14) for complexes formed by endotoxin (lipopolysaccharide, LPS) and a plasma
      LPS-binding protein (LBP). We compared monocytes obtained from normal controls
      with those obtained from septic patients for expression of CD14 by flow
      cytometric analysis of immunofluorescent-stained cells. In normal individuals and
      patients, 75%-95% of monocytes are CD14 positive (CD14+). Mean fluorescence
      exhibited by the CD14+ population was measured after maintaining cells at 37
      degrees C for 15 minutes and compared with baseline cells held at 4 degrees C
      (mean fluorescence ratio). All cells increased their CD14 mean fluorescence ratio
      with warming; however, the level achieved by monocytes obtained from septic
      patients was on average 78% +/- 8% of control levels (p = 0.014). To further
      clarify CD14 expression, we examined the effect of Escherichia coli LPS on normal
      monocytes by comparing monocytes treated in serum-free buffer (no LBP) with
      monocytes treated in whole blood (containing LBP). The LPS (1.0 ng/mL) incubated
      with whole blood for 120 minutes generated an increase in CD14+ mean fluorescence
      compared with buffer. In contrast, phorbol myristate acetate lowered CD14+ mean
      fluorescence levels. These data indicate that normal monocytes incubated in the
      presence of ligand (LBP-LPS complexes) increase their expression of CD14, whereas
      CD14 expression in septic patients is diminished. We conclude that monocytes from
      septic patients were responsive to other stimuli aside from LPS and that
      decreased expression of CD14 may indicate a poor prognosis.

PMID- 1373778
TI  - The relative proportion of stromal and epithelial hyperplasia is related to the
      development of symptomatic benign prostate hyperplasia.
AB  - The specific features of the prostate adenoma predisposing to the development of
      symptomatic benign prostatic hyperplasia (BPH) are unknown. Our objective was to
      determine whether the histological composition of the prostate adenoma is related
      to the development of symptomatic BPH. Prostate adenomas were obtained from men
      with asymptomatic BPH undergoing cystoprostatectomy for invasive transitional
      cell carcinoma, and from men with symptomatic BPH undergoing open prostatectomy,
      transurethral resection of the prostate and pharmacotherapy. The severity of
      bladder outlet obstruction was evaluated with the Boyarsky symptom score and
      uroflowmetry. The percentages of stroma, epithelium and glandular lumen were
      determined in the prostate adenomas via quantitative image analysis on a computer
      assisted morphometry system. The prostate adenomas from the 33 men with
      symptomatic BPH contained 62 +/- 1%, 15 +/- 1% and 23 +/- 1 of stroma, epithelium
      and glandular lumen, respectively. The prostate adenomas from 6 men with
      asymptomatic disease contained 54 +/- 1%, 21 +/- 1% and 25 +/- 1% of stroma,
      epithelium and glandular lumen, respectively. The ratios of stromal-to-epithelial
      hyperplasia in the prostate adenomas from men with symptomatic and asymptomatic
      disease were 4.6 +/- 0.3 and 2.7 +/- 0.1, respectively. The differences in
      percentage of stroma and epithelium, and the stromal-to-epithelial ratio in the
      prostate adenomas from men with symptomatic and asymptomatic BPH were
      statistically significant. Our study suggests that the histological composition
      of the prostate adenoma is related to the development of symptomatic BPH.

PMID- 1373779
TI  - The clinical effects of a 5 alpha-reductase inhibitor, finasteride, on benign
      prostatic hyperplasia. The Finasteride Study Group.
AB  - Finasteride (Proscar--an orally active 5 alpha-reductase enzyme inhibitor) blocks
      the conversion of testosterone to dihydrotestosterone. The effects of finasteride
      in patients with benign prostatic hyperplasia were investigated in 2 double
      blind, placebo-controlled studies. In study 1, 86 patients were treated with
      placebo or finasteride (5 to 80 mg. per day) for 12 weeks, followed by a 12-week
      drug-free period. After 12 weeks of treatment all doses of finasteride showed
      significant decreases in prostate volume. However, 12 weeks after discontinuation
      of finasteride prostate volume returned to near baseline values. In study 2, 104
      patients were treated with placebo or finasteride (0.2 to 40 mg. per day) for 24
      weeks. After 24 weeks of finasteride treatment prostate volume showed a mean
      decrease of 24% and 28% (p less than 0.01) in the 1 and 5 mg. groups,
      respectively. Lower doses had a lesser effect on prostate shrinkage. Maximum
      urinary flow showed a mean increase of 3.7 cc per second when the 1 and 5 mg.
      groups were combined. Symptom improvement was observed in the 1 and 5 mg. groups,
      although this was not statistically different from the placebo group due to the
      small sample size.

PMID- 1373780
TI  - Two cases of eosinophilic cystitis induced by tranilast.
AB  - We report 2 cases of eosinophilic cystitis induced by Tranilast, which was used
      for the treatment of bronchial asthma. In case 2 Tranilast itself and its
      metabolic derivative proved to be inciting agents by a drug-induced lymphocyte
      stimulation test. The literature on this association is reviewed.

PMID- 1373781
TI  - The detection of prostate specific antigen, MHS-5, and other markers in invasive
      prostate cancer and seminal vesicle.
AB  - Prostate specific antigen (PSA) is the most useful serum marker for following the
      disease status of prostate cancer patients after therapy. While PSA is felt to be
      an organ specific marker, lack of PSA expression in the seminal vesicles has not
      been adequately established. MHS-5 is a monoclonal antibody which recognizes an
      epitope on seminal vesicle specific antigen. Our objectives were to define PSA
      expression by the seminal vesicles, to determine whether MHS-5 could serve as an
      adjunct in the diagnosis of seminal vesicles invasion by carcinoma of the
      prostate, and to determine whether carcinoma, having invaded seminal vesicles
      would retain its expression of PSA and other prostate markers. Using an
      immunoperoxidase procedure, we studied thirteen seminal vesicles without
      histologic evidence of prostate cancer invasion and five seminal vesicles with
      locally invasive cancer. No seminal vesicles expressed PSA, whereas prostate
      cancer invading the seminal vesicles expressed PSA in all cases. MHS-5 expression
      was more variable. Only two of five cases of locally invasive tumor demonstrated
      seminal vesicles expression for MHS-5. Our findings further support the
      specificity of PSA. While MHS-5 may be helpful in delineating seminal vesicles in
      some instances, it is not a consistently reliable marker.

PMID- 1373783
TI  - [A morphological study of pulmonary macrophages in bleomycin-injected murine
      models].
AB  - Pulmonary changes induced in a murine model by intraperitoneal injections of
      bleomycin were morphologically studied by light and electron microscopy. The
      number of pulmonary macrophages and the distribution of fibronectin in these
      cells were evaluated by acid phosphatase and affinity staining using anti
      fibronectin horseradish peroxidase conjugates. The onset of acute inflammation
      occurred 4 days after intraperitoneal injection of bleomycin and reached its peak
      on the 14th day post-injection. The inflammatory reaction then gradually
      decreased. Areas of subpleural fibrosis was observed on day 42. On day 14, the
      ratio of the macrophage in bleomycin-treated mice to that in control mice was
      5:1. Many activated and foamy macrophages were observed at that time. These
      findings indicate that macrophage turnover activity is remarkably increased
      during the acute inflammatory phase. Fibronectin was detected in the cytoplasm of
      macrophages on day 14, 21, and 28. It was also detected in both alveolar
      capillary and epithelial basal lamina as well as in interstitial collagen fibers.
      On day 42, fibronectin staining was strongly positive in areas of subpleural
      fibrosis. These results suggest that fibronectin released from pulmonary
      macrophages plays a role in the process of pulmonary fibrosis.

PMID- 1373782
TI  - Distribution of nerve growth factor-like protein and nerve growth factor receptor
      in human benign prostatic hyperplasia and prostatic adenocarcinoma.
AB  - Recent observations from our laboratory have identified a nerve growth factor
      (NGF)-like protein in conditioned media of stromal cells and neoplastic
      epithelial cells of the human prostate which mediates paracrine interactive
      growth of both cell types in vitro. In order to investigate the location of this
      NGF-like protein in the human prostate in vivo, and whether a nerve growth factor
      receptor (NGF-R) could be identified, we have carried out immunocytochemical
      studies on frozen tissue sections of human benign prostatic hyperplasia (BPH),
      prostatic adenocarcinoma and normal prostatic tissue. The NGF-like protein
      localized predominantly to the stromal component of BPH, adenocarcinoma and
      normal (non-cancerous) prostatic tissue. Conversely, the NGF-R localized
      predominantly to the epithelial cells of these tissues. Renal tissue provided
      negative controls for both the NGF-like protein and the NGF-R. The testis
      provided positive controls for both the NGF-like protein and the NGF-R. These
      results provide corroborative evidence for a NGF-like protein produced by stromal
      cells which interacts with a NGF-R on the adjacent epithelial cells thereby
      mediating paracrine interactive growth regulation of the human prostate.

PMID- 1373784
TI  - Transmembrane electrical potential of lymphocytes in ageing mice. Flow cytometric
      analysis of mitogen-stimulated cells.
AB  - The changes in transmembrane electrical potential (TMP) of Concanavalin A (Con-A)
      stimulated lymphocytes from young adult and aged CBA/Ca mice were studied with a
      potential-sensitive fluorescent oxonol probe. The initial effect of Con-A was to
      depolarise lymphocytes from young mice and abrogated in the presence of
      tetraethylammonium chloride (TEA), an inhibitor of K(+)-selective channels. Young
      and old T lymphocytes both responded to the calcium ionophore A23187 by becoming
      hyperpolarized, but this occurred more slowly in the old cells. While treated
      with the ionophore, old B cells appeared to be limited in their ability to
      depolarize in the presence of high external K+ concentrations, which did not hold
      for T cells of old animals. One or more defects in the mechanisms of monovalent
      ion transport across the membrane of old lymphocytes are probably responsible for
      these differences and may be associated with the known age-related dysfunction of
      the immune system.

PMID- 1373785
TI  - [Communication in palliative medicine].

PMID- 1373786
TI  - Detection of mycobacterial rRNA in sarcoidosis with liquid-phase hybridisation.
AB  - Because sarcoidosis resembles tuberculosis clinically and histologically, it has
      been suggested that mycobacteria might have a role in the pathogenesis of the
      disorder. Mycobacteria have not been found in sarcoid tissues by conventional
      culture techniques, so we have used a liquid-phase hybridisation method to see
      whether we could detect mycobacterial rRNA in such tissues. RNA was extracted
      from five sarcoid and five normal spleens. Extracts were assayed by liquid-phase
      DNA/RNA hybridisation with a DNA probe specific for the rRNA of the Mycobacterium
      tuberculosis complex. Hybridisation obtained with the sarcoid spleens, from which
      mycobacteria were neither seen on microscopy nor cultured with standard methods,
      was 4.8 times higher than that with normal spleens (p less than 0.001). Our
      demonstration of mycobacterial nucleic-acid components in sarcoid splenic tissues
      supports the notion that mycobacteria play a part in the cause of sarcoidosis.

PMID- 1373787
TI  - Plasmapheresis for severe, unremitting, chronic urticaria.
AB  - Histamine-releasing autoantibodies have been identified in chronic idiopathic
      urticaria. 8 patients with severe disease and histamine-releasing activity in
      their sera underwent plasmapheresis. Symptoms were abolished for 2 months in 1
      patient and for 3 weeks in another, 2 showed almost complete resolution of
      symptoms, 2 had temporary relief, and the other 2 showed little change. Further
      investigation in 4 of the patients showed significantly reduced skin-test
      responses to fresh post-exchange autologous sera after plasmapheresis compared
      with stored pre-exchange sera, but the response to intradermal histamine remained
      unchanged. Blood cellular histamine increased as in-vitro serum histamine
      releasing activity fell after plasmapheresis. These results favour a pathogenetic
      role for histamine-releasing autoantibodies in patients with chronic urticaria.

PMID- 1373788
TI  - Urinary excretion of 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophol after
      oral loading with serotonin.
AB  - The urinary excretion patterns of the serotonin (5-hydroxytryptamine; 5-HT)
      metabolites 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5
      HTOL) were examined after ingestion of bananas, a food rich in 5-HT. The bananas
      contained on an average 25 micrograms 5-HT/g pulp. Both urinary 5-HIAA and 5-HTOL
      increased markedly (15- to 30-fold) shortly after eating 3-4 bananas, with the
      highest concentrations found in urine specimens collected after 2-4 h, and did
      not return to normal until after 8-10 h. The excretion of 5-HIAA increased from a
      control mean value of 3.9 mg/24 h to 12.7 mg/24 h, when conventional diets were
      supplemented with 3-4 bananas. The corresponding results for 5-HTOL were 16.8
      micrograms/24 h and 60.7 micrograms/24 h, respectively. Of the banana-derived 5
      HT ingested, 60-80% was recovered in the urine as 5-HIAA and only 0.3-0.5% as 5
      HTOL. However, since both the time-course and relative increase in 5-HTOL was
      similar to that of 5-HIAA, there was no effect on the urinary 5-HTOL to 5-HIAA
      ratio. By contrast, acute alcohol consumption produced a considerable elevation
      of this ratio.

PMID- 1373789
TI  - Comparative effects of galanin on isolated smooth muscle cells from ileum in five
      mammalian species.
AB  - Effect of galanin and CCK8 were studied on isolated smooth muscle cells obtained
      from pig, guinea-pig, rat, rabbit and dog ileum circular muscle layer. Galanin as
      well as CCK8 induced a concentration-dependent contraction of pig, rat, rabbit
      and guinea-pig ileum smooth muscle cells. Maximal contraction ranged between 23.7
      +/- 1.9% and 26.1 +/- 3.1% decrease in cell length from control in the presence
      of both peptides. This maximal contraction was obtained at 1 nM galanin in pig,
      rat, rabbit, 1 nM CCK8 in rat, rabbit, guinea-pig, at 10 nM galanin in guinea-pig
      and 10 nM CCK8 in pig. Concentrations of galanin inducing a half maximal
      contraction (EC50) ranged between 8 pM and 80 pM in these species. In dog, CCK8
      induced a concentration-dependent contraction of ileum smooth muscle cells, with
      a maximal contraction (24.5 +/- 2.3%) at 1nM and an EC50 of 50 pM while galanin
      inhibited cell contraction induced by CCK8. The CCK-induced contraction was
      abolished at 10 nM galanin and 10 nM VIP. Concentrations of galanin and VIP
      inducing a half-maximal relaxation of contracted cells were 2 pM and 3 pM
      respectively. It is concluded that galanin may induce cell contraction of pig,
      guinea-pig, rat and rabbit ileum circular muscle layer and cell relaxation of dog
      ileum by a direct myogenic effect.

PMID- 1373790
TI  - Role of nitric oxide in lower esophageal sphincter relaxation to swallowing.
AB  - Studies were performed in the opossum to define the role of the L-arginine-nitric
      oxide (NO) pathway in lower esophageal sphincter (LES) relaxation to swallowing
      and vagal stimulation in viv and intramural nerve stimulation in vitro. In vivo,
      L-NAME, a water soluble NO synthase (NOS) inhibitor, caused antagonism of LES
      relaxation due to reflex-induced swallowing. L-NAME (20 mg/kg i.v.) reduced the
      amplitude of swallow induced relaxation from 88% to 28%. LES relaxation due to
      electrical stimulation of peripheral end of decentralized vagus nerve was also
      antagonized. The effects of L-NAME were reversed by L-arginine, but not by D
      arginine. L-NAME treatment did not antagonize LES relaxation to intravenous
      administration of isoproterenol. In vitro, NO and sodium nitroprusside (SNP)
      caused a decrease in the sphincter tone. The relaxing effect caused by NO and SNP
      was not antagonized by tetrodotoxin or omega-conotoxin. Inhibitors of NO
      synthase, L-NMMA and L-NNA, caused slight increase in the spontaneous resting LES
      tone and concentration-dependent antagonism of electrical field stimulation (EFS)
      induced LES relaxation. L-NNA (10(-4)M) abolished EFS induced LES relaxation at
      low frequencies (less than 5 Hz) and antagonized the relaxation to a value 20% of
      the control at 20 Hz. The antagonistic action of L-NMMA and L-NNA was unaffected
      by D-arginine but was reversed by L-arginine. The inhibitory effect of NO, SNP,
      or two other putative inhibitory neurotransmitters (VIP and CGRP) on the LES was
      not antagonized by L-NNA. These studies show that inhibitors of NO synthase
      selectively antagonize LES relaxation to all three modes of intramural inhibitory
      nerve stimulation including physiological swallowing. These studies suggest that
      the L-arginine-nitric oxide pathway is involved in physiological relaxation of
      the LES.

PMID- 1373791
TI  - In vivo dynamic MR imaging of MBP-induced acute experimental allergic
      encephalomyelitis in Lewis rat.
AB  - A dynamic in vivo study by MRI consisting of the measurement of relaxation times
      and in the visualization of the BBB permeability by Gd-DOTA was performed in an
      MBP-induced acute EAE model of Lewis rat. Fourteen rats were immunized with an
      MBP/CFA mixture, eight by CFA alone, and three control rats were used to test the
      harmless effect of repeatedly performed MRI examinations. Beginning on the 8th or
      9th days and in parallel with the emergence of clinical signs, rats immunized by
      the MBP/CFA mixture showed slight increases of relaxation times and of the BBB
      permeability. These abnormalities, which always remain localized in the
      periventricular regions, become more pronounced toward the 10th and 11th days,
      just before (or at the same time) as paraplegia manifestations. After a plateau
      of a few days, they diminish with the clinical signs. This close correlation
      found in vivo establishes the essential role of BBB in the pathogenesis of
      clinical signs of this EAE model.

PMID- 1373792
TI  - Continuous local intraarterial infusion after prolonged arterial stasis in the
      fingers and toes.
AB  - Seven patients with trauma to eight digits and one toe went untreated for
      arterial stasis, with subsequent development of posttraumatic changes in skin
      coloration. In two patients involving two digits, a daily dose of 2,000 ml
      containing 240,000 U urokinase, 80 micrograms prostaglandin E1, and 10,000 U
      heparin in lactated Ringer's solution was administered by intravenous infusion
      for 10 consecutive days; one of the two digits became necrotic. In all subsequent
      patients, a daily dose of 80 ml containing 240,000 U urokinase, 40 micrograms
      prostaglandin E1, 10,000 U (maximum) heparin, and low-molecular-weight dextran
      was administered by continuous local intraarterial infusion for 10 consecutive
      days. These seven extremities survived, even in the case of two digits and one
      toe with over 50 hr of arterial stasis. We believe that revascularization of
      extremities following prolonged periods of arterial stasis may be possible by
      means of continuous local intraarterial infusion of antithrombotic agents.

PMID- 1373793
TI  - Substance P and multiple sclerosis.
AB  - Multiple sclerosis is an inflammatory disease which affects the white matter of
      the central nervous system (CNS). The aetiology of this condition is unknown but
      it is generally believed to represent an autoimmunological response to a
      component of myelin triggered by an environmental factor, in a genetically
      susceptible individual. The natural history of the disease, in terms of clinical
      disability, is unpredictable, and the factors responsible unknown. Substance P is
      an undecapeptide that acts as a neurotransmitter in the CNS and as a regulator of
      immune responses. The recent discovery of substance P immunoreactive astrocytes
      in multiple sclerosis plaques raises the possibility that this peptide may be
      important both in the development of plaques and in governing the natural history
      of the disease.

PMID- 1373794
TI  - Theoretical mechanisms for synthesis of carcinogen-induced embryonic proteins:
      XXVII. Intermediate generalizations (Part B).
AB  - In this second section of generalizations, methylation, differentiation and
      carcinogenesis are reviewed. Special consideration is given to the alpha
      fetoprotein gene which is used extensively as a model embryonic gene. Specific
      correlations are made between the glucocorticoid response element and the alpha
      fetoprotein gene. A further correlation was made between retinoic acid and alpha
      fetoprotein synthesis.

PMID- 1373795
TI  - Functional interactions between two Ca2+ channel activators, (S)-Bay K 8644 and
      FPL 64176, in smooth muscle.
AB  - We examined the interactions of two Ca2+ channel activators, (S)-Bay K 8644 and
      FPL 64176, on smooth muscle L-type Ca2+ channels. FPL 64176 (300 nM) caused a
      sustained contraction of rat tail artery strips. This contractile response was
      inhibited by approximately 70% by (S)-Bay K 8644 (EC50 = 14 nM). (S)-Bay K 8644
      (100 nM) increased whole-cell Ca2+ currents in A7r5 smooth muscle cells but
      effectively blocked further stimulation by 1 microM FPL 64176. When added alone,
      1 microM FPL 64176 increased Ca2+ channel current amplitude, slowed current
      activation, and prolonged tail current duration. Furthermore, no inactivation of
      current during step depolarizations was observed in the presence of FPL 64176.
      After subsequent addition of (S)-Bay K 8644, Ca2+ channel current activation was
      accelerated and tail current duration was shortened. Additionally, pronounced
      inactivation of the Ca2+ channel current became apparent. These results are
      consistent with a negative allosteric interaction between the (S)-Bay K 8644
      binding site and that of FPL 64176, in smooth muscle.

PMID- 1373796
TI  - Calcium directly permeates kainate/alpha-amino-3-hydroxy-5-methyl-4-
      isoxazolepropionic acid receptors in cultured cerebellar Purkinje neurons.
AB  - In cultures of rat cerebellar neurons that were enriched in Purkinje cells, the
      non-N-methyl-D-aspartate glutamate receptor agonist kainate (KA) stimulated Ca2+
      influx into all neurons in Na(+)-containing solutions. A large Ca2+ influx was
      also observed in most neurons when KA was applied in Na(+)-free solutions, even
      when the cells were voltage-clamped at negative potentials. KA also stimulated
      Co2+ uptake into both Purkinje and non-Purkinje neurons. The KA-induced Ca2+
      influx was insensitive to pharmacological antagonists of voltage-sensitive Ca2+
      channels and antagonists of N-methyl-D-aspartate receptors. Thus, different types
      of cerebellar neurons possess KA-gated ionophores that are permeable to Ca2+.
      This Ca2+ conductance may play an important role in glutamate-mediated
      physiological and pathological events in the cerebellum.

PMID- 1373797
TI  - Regulation and subcellular location of nitrogen oxide synthases in RAW264.7
      macrophages.
AB  - In nitrinergic signal transduction, nitrogen oxide (NO) synthases (NOS) (EC
      1.14.23) catalyze the conversion of L-arginine to L-citrulline and NO, which in
      turn activates soluble guanylyl cyclase. Macrophages were reported to contain a
      single isoform of NOS (type II, soluble, Ca(2+)-independent, 130-kDa) and only
      upon activation of the cells by interferon-gamma (INF) and lipopolysaccharides
      (LPS). By a mechanism involving L-type Ca2+ channels, calmodulin, and serine
      proteases, INF/LPS also induce a cytotoxic activation of macrophages. In RAW264.7
      macrophages, NO release was detected upon activation of the cells by INF/LPS but
      also, although at a 20-fold lower level, in control cells. The latter
      constitutive NOS activity and NO release were Ca2+ dependent and were decreased
      in INF/LPS-activated RAW264.7 cells or with increasing passage number. RAW264.7
      cells did not express soluble guanylyl cyclase, suggesting other target molecules
      for NO. In INF/LPS-activated cells, NOS activities and NO release were Ca2+
      independent (type II) and coinduced with NADPH-diaphorase activities both in the
      soluble and in the particulate fractions. The NOS-II activities corresponded to a
      130-kDa protein, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      which was not recognized in a protein immunoblot with anti-NOS-I antibody. The
      serine protease inhibitor tosyl-lysyl chloromethyl ketone abolished the induction
      of NOS-II by INF/LPS, by depleting intracellular thiol pools and interfering with
      protein synthesis. Induction of NOS-II by INF/LPS was transcriptionally based
      and, for maximal enzyme activity, required increased intracellular
      tetrahydrobiopterin levels, intracellular Ca2+ mobilization, and activation of
      non-L-type Ca2+ channels but, unlike the induction of macrophage-mediated
      cytotoxicity, neither L-type-Ca2+ channels nor calmodulin.

PMID- 1373799
TI  - Role of NAD(P)H:(quinone acceptor) oxidoreductase (DT-diaphorase) in activation
      of mitomycin C under hypoxia.
AB  - The role of the two-electron reducing enzyme DT-diaphorase in the activation of
      mitomycin C under hypoxic conditions was investigated. Mitomycin C activity was
      compared in L5178Y murine lymphoblasts, which have low levels of DT-diaphorase
      activity, and L5178Y/HBM10 cells, which have elevated levels of enzyme activity.
      The cytotoxic and DNA cross-linking activities of mitomycin C were greater in
      L5178Y/HBM10 cells than in L5178Y cells. In L5178Y/HBM10 cells, dicoumarol, an
      inhibitor of DT-diaphorase, decreased cell kill and DNA cross-linking by
      mitomycin C in air but had no significant effect on these activities under
      hypoxia. By comparison, in L5178Y cells, dicoumarol had no effect on drug
      activity under either aerobic or hypoxic conditions. A model for the activation
      of mitomycin C by both one-electron and two-electron reduction is proposed. Our
      findings suggest that two-electron reduction by DT-diaphorase has only a limited
      role in the activation of mitomycin C under hypoxic conditions, although this
      enzyme appears to be an important contributor to drug activation under aerobic
      conditions.

PMID- 1373798
TI  - Late-stage spermatids are characterized by expression of the "liver-specific"
      asialoglycoprotein receptor, RHL-1.
AB  - The major and minor forms of the asialoglycoprotein receptor (ASGP-R), designated
      in the rat as RHL-1 and RHL-2/3, respectively, have traditionally been considered
      to be expressed exclusively in hepatic parenchymal cells. Northern blot analysis
      now demonstrates that rat and mouse testis express a receptor similar to the RHL
      1 ASGP-R but not the RHL-2/3 receptor. In situ hybridization studies demonstrate
      that late-stage mouse and rat spermatids are the testicular cells that express
      the RHL-1 ASGP-R. The rat spermatid RHL-1 receptor has functional binding
      capability, with a KD of approximately 1.4 x 10(-8) M, and similar
      characteristics, compared with the hepatic RHL-1 receptor, regarding ligand
      binding specificity and ion dependence. These findings have major implications
      for therapeutic procedures attempting to target cytotoxic agents or DNA to
      hepatocytes using the ASGP-R. In addition, these findings demonstrate that late
      stage spermatids are transcriptionally active and suggest that the RHL-1 receptor
      may have a functional role in sperm maturation and/or fertilization.

PMID- 1373800
TI  - Structure of the gamma-less nicotinic acetylcholine receptor: learning from
      omission.
AB  - The nicotinic acetylcholine receptor can be expressed in Xenopus oocytes by
      injection of in vitro synthesized RNA for the alpha, beta, gamma, and delta mouse
      muscle subunits. However, detectable responses can also be obtained by injection
      of alpha, beta, and delta subunit RNA only. The receptors expressed in this case
      (gamma-less receptors) share many of the properties of the normal receptor,
      including relaxation time constants, Hill slope, and relative permeability for
      Na+, K+, Cs+, and Tris+. The major single-channel conductances of alpha beta
      gamma delta and alpha beta delta receptors are similar (34.2 +/- 2.9 and 38.5 +/-
      0.6 pS, respectively) but clearly different from the major conductances seen
      after the combined injection of alpha beta delta mouse subunit RNA and Xenopus
      gamma subunit RNA. Mutations in the second transmembrane segment of the alpha and
      beta subunits, known to affect open time and blockade by QX-222, are equally
      effective in the gamma-less receptor. These data strongly suggest that the gamma
      less receptor has the same pore diameter as the normal receptor and that alpha,
      beta, and delta subunits participate in its formation. Injection of alpha beta
      gamma delta well as alpha beta delta RNA produced additional subconductance
      states of around 25 pS. The low conductance state was sensitive to mutations
      introduced in the alpha or beta subunits with or without the gamma subunit,
      indicating that this channel did not need the gamma subunits but required at
      least the alpha and beta subunits to be produced. Injection of alpha beta delta
      and the adult-type epsilon subunit RNA gave rise to channels with conductances of
      35 and 55 pS when the stoichiometry of the injection was 2:1:1:1, but only the 55
      pS channel was recorded when the epsilon subunit RNA concentration was increased
      by 10-fold (stoichiometry of 2:1:1:10). The gamma-less receptor can thus be
      expressed even when the adult epsilon subunit is present. Whether gamma-less
      receptors are expressed at normal adult neuromuscular junctions remains unknown.

PMID- 1373801
TI  - Arcaine blocks N-methyl-D-aspartate receptor responses by an open channel
      mechanism: whole-cell and single-channel recording studies in cultured
      hippocampal neurons.
AB  - Arcaine, a putative competitive antagonist at the polyamine site on the N-methyl
      D-aspartate (NMDA) receptor complex, not only inhibits polyamine enhancement of
      NMDA-induced [3H]dizocilpine (MK-801) binding but also depresses binding in the
      absence of polyamines. In the present experiments, we investigated the mechanism
      of this latter effect in whole-cell and single-channel recordings from cultured
      rat hippocampal neurons. Arcaine produced a concentration-dependent block of NMDA
      evoked inward currents (KD, 61 microM at -60 mV) but not those induced by
      kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, or gamma
      aminobutyric acid. The arcaine block was strongly voltage dependent and was
      almost completely relieved at positive holding potentials. Analysis of the
      voltage dependence indicated that the arcaine acceptor site appeared to sense 67%
      of the transmembrane electric field. In support of an open channel blocking
      mechanism, arcaine, like Mg2+, prevented dizocilpine from blocking the NMDA
      receptor channel. Moreover, increasing the dizocilpine concentration partially
      overcame the arcaine effect, indicating a competitive interaction between arcaine
      and dizocilpine. Spermine, which in our preparation usually produced only an
      arcaine-like voltage-dependent block of NMDA currents at high concentrations
      (greater than 100 microM), had no effect on the block by arcaine at lower
      concentrations. In single-channel recordings, arcaine caused a concentration- and
      voltage-dependent decrease in apparent channel amplitude. Assuming a simple model
      of open channel block, we estimate the arcaine binding and unbinding rates as 4.4
      x 10(8) M-1 sec-1 and 1.8 x 10(4) sec-1, respectively, which are comparable to
      the rates for open channel block by Zn2+ and substantially faster than those of
      Mg2+. These results indicate that arcaine inhibits NMDA-induced [3H]dizocilpine
      binding by blocking the open NMDA receptor channel, an action that is independent
      of the polyamine site.

PMID- 1373802
TI  - Antagonists that demonstrate species differences in neurokinin-1 receptors.
AB  - 125I-Bolton-Hunter-substance P (125I-BH-SP) binding properties of three novel
      classes of neurokinin-1 (NK-1) receptor antagonists were investigated in tissues
      derived from humans, guinea pigs, and rats. 125I-BH-SP was shown to bind to a
      single class of binding sites, with similar dissociation constants, Kd, in human
      astrocytoma cells (U-373 MG), human urinary bladder, guinea pig forebrain, guinea
      pig ileum longitudinal smooth muscle, rat forebrain, and rat duodenum. In each
      tissue preparation, known peptide agonists and peptide antagonists yielded
      potencies typical for a NK-1 receptor profile, with little difference in binding
      properties between the various tissues. However, when the three classes of
      compounds, heterosteroids, cyanines, and modified peptides, were tested for their
      ability to displace 125I-BH-SP binding from the NK-1 receptor, very different
      binding profiles were observed. The heterosteroids were shown to be as much as 3
      orders of magnitude more potent in tissues derived from rats than from humans or
      guinea pigs. A distinct species-dependent structure-activity relationship (SAR)
      was also observed for this class of compounds. Like the heterosteroids, the
      cyanines displaced 125I-BH-SP with 10-30-fold higher affinity in rat tissues than
      in human and guinea pig tissues. However, the SAR generated by the cyanines was
      comparable in all tissues studied. The modified peptides, on the other hand, were
      up to 10-100-fold more potent in human and guinea pig than rat tissues, producing
      a SAR that differed between the various species. No differences in binding
      properties between central nervous system and peripheral tissues from the same
      species were seen with these compounds. These results provide evidence for
      species differences in NK-1 receptors in humans, guinea pigs, and rats. Because
      it is known that there exists great sequence identity between rat and human NK-1
      receptors, it is hypothesized that key amino acid changes or different lipid
      environments within the transmembrane binding region of the receptor may account
      for the observed species difference. Furthermore, this study emphasizes that
      caution is necessary in the choice of species to be used in development programs
      targeted towards therapeutic entities in the NK-1 receptor antagonist area.

PMID- 1373803
TI  - A high-mobility-group protein and its cDNAs from Drosophila melanogaster.
AB  - We have identified, purified, and characterized a high-mobility-group (HMG)
      protein and its cDNAs from Drosophila melanogaster. This protein, HMG D, shares
      most of the characteristics of vertebrate HMG proteins; it is extractable from
      nuclei with 0.35 M NaCl, is soluble in 5% perchloric acid, is relatively small
      (molecular weight of 12,000), has both a high basic (24%) and high acidic (24%)
      amino acid content, and is a DNA-binding protein. HMG D exhibits characteristics
      of both the vertebrate HMG 1 and 2 class and the HMG 14 and 17 class of proteins.
      Its amino acid sequence is similar (36% amino acid identity) to that of HMG1,
      while its size and selective extraction with ethidium bromide are similar to
      properties of the HMG 14 and 17 class of proteins. HMG D is encoded by a single
      copy gene that maps to 57F8-11 on the right arm of chromosome 2. Two transcripts
      are observed during embryogenesis; the protein is relatively stable throughout
      development. By the biochemical criteria of size, solubility, and amino acid
      content, HMG D appears to be the major HMG protein of D. melanogaster.

PMID- 1373804
TI  - Guide RNAs for transcripts with developmentally regulated RNA editing are present
      in both life cycle stages of Trypanosoma brucei.
AB  - RNA editing of several mitochondrial transcripts in Trypanosoma brucei is
      developmentally regulated. The cytochrome b and cytochrome oxidase II mRNAs are
      edited in procyclic-form parasites but are primarily unedited in bloodstream
      forms. The latter forms lack the mitochondrial respiratory system present in
      procyclic forms. Editing of the NADH dehydrogenase 7 (ND7) and ND8 transcripts is
      also developmentally regulated but occurs preferentially in bloodstream forms.
      Other transcripts, cytochrome oxidase III and ATPase 6, are edited in both life
      forms. We have identified many minicircle-encoded guide RNAs (gRNAs) for ATPase
      6, ND7, and ND8. The characteristics of these gRNAs reveal how extensively edited
      RNA can be edited in the 3'-to-5' direction. Northern (RNA) blot and primer
      extension analyses indicate that gRNAs for transcripts whose editing is
      developmentally regulated are present in both procyclic and bloodstream form
      parasites. These results suggest that the developmental regulation of editing in
      these transcripts is not controlled by the presence or absence of gRNAs.

PMID- 1373805
TI  - A single beta-globin locus control region element (5' hypersensitive site 2) is
      sufficient for developmental regulation of human globin genes in transgenic mice.
AB  - The beta-globin gene complex is regulated by an upstream locus control region
      (LCR) which is responsible for high-level, position-independent, erythroid-cell
      specific expression of the genes in the cluster. Its role in the developmental
      regulation of beta-like globin gene transcription remains to be established. We
      have examined the effect of a single LCR element, hypersensitive site 2 (HS2), on
      the developmental regulation of the human fetal gamma and adult beta genes in
      transgenic mice. In mice bearing HS2A gamma beta and HS2G gamma A gamma-117 delta
      beta human globin gene constructs, switching from gamma- to beta-gene expression
      begins at about day 13.5 of gestation and is largely completed shortly after
      birth. The larger construct also demonstrates a switch in G gamma- to A gamma
      gene expression during the gamma-to-beta switch similar to that observed during
      normal human development. We conclude that HS2 alone is sufficient for
      developmental regulation of the human beta-globin genes.

PMID- 1373806
TI  - Stability of Drosophila RNA polymerase II elongation complexes in vitro.
AB  - We show that nuclear extract from Drosophila Kc cells supports efficient
      elongation by RNA polymerase II initiated from the actin 5C promoter. The
      addition of 0.3% Sarkosyl, 1 mg of heparin per ml, or 250 mM KCl immediately
      after initiation has two effects. First, the elongation rate is reduced 80 to 90%
      as a result of the inhibition of elongation factors. Second, there is an increase
      in the amount of long runoff RNA, suggesting that there is an early block to
      elongation that is relieved by the disruptive reagents. Consistent with the first
      effect, we find that the ability of factor 5 (TFIIF) to stimulate the elongation
      rate is inhibited by the disruptive agents when assayed in a defined system
      containing pure RNA polymerase II and a dC-tailed template. The disruptive agents
      also inhibit the ability of DmS-II to suppress transcriptional pausing but only
      slightly reduce the ability of DmS-II to increase the elongation rate twofold.
      The pause sites encountered by RNA polymerase II after initiation at a promoter
      and subsequent treatment with the disruptive reagents are also recognized by pure
      polymerase transcribing a dC-tailed template. It has been suggested that 5,6
      dichloro-1-beta-D-ribofuranosylbenzimidazole inhibits RNA polymerase II during
      elongation, but we find that the purine nucleoside analog has no effect on
      elongation complexes containing RNA over 500 nucleotides in length or on the
      action of factor 5 or DmS-II in the defined system.

PMID- 1373807
TI  - Maxicircle CR1 transcripts of Trypanosoma brucei are edited and developmentally
      regulated and encode a putative iron-sulfur protein homologous to an NADH
      dehydrogenase subunit.
AB  - The maxicircle of Trypanosoma brucei encodes components of the mitochondrial
      oxidative phosphorylation system, as do other mitochondrial DNAs, but maxicircle
      gene identification is complicated by extensive editing of some transcripts. We
      found that transcripts from the CR1 region were extensively edited, as are other
      transcripts from maxicircle regions which exhibit strong G versus C strand bias.
      Editing added 259 uridines and removed 46 uridines to produce an approximately
      574-nucleotide mature mRNA. Partially edited cDNAs and potential guide RNAs were
      also characterized. Initiation and termination codons were created, and they
      defined an open reading frame encoding a predicted protein of 145 amino acids.
      This protein contains two iron-sulfur cysteine motifs and is homologous to a
      subunit of NADH dehydrogenase and to other electron-carrier proteins. Higher
      levels of both edited and unedited CR1 transcripts accumulated in bloodstream
      forms of the parasite than in procyclic forms, suggesting developmental
      regulation of CR1 gene expression.

PMID- 1373808
TI  - Mechanism and consequences of the duplication of the human C4/P450c21/gene X
      locus.
AB  - The adjacent C4 and P450c21 genes encode the fourth component of serum complement
      and steroid 21-hydroxylase respectively, and are tandemly duplicated in the
      human, murine, and bovine genomes. We recently cloned a cDNA for another
      duplicated gene, operationally termed X, which overlaps the 3' end of human
      P450c21 and has the opposite transcriptional orientation. Thus, the organization
      of the locus is 5'-C4A-21A-XA-C4B-21B-XB-3' (Y. Morel, J. Bristow, S. E.
      Gitelman, and W. L. Miller, Proc. Natl. Acad. Sci. USA 86:6582-6586, 1989). To
      determine how this locus was duplicated, we sequenced the DNA at the duplication
      boundaries and the 7 kb between P450c21A and C4B comprising the XA locus. The
      sequences located the duplication boundaries precisely and indicate that the
      duplication occurred by nonhomologous recombination. The boundaries are
      substantially different from those of the corresponding duplication in the mouse
      genome, suggesting that similar gene duplications may have occurred independently
      in ancestors of rodents and primates after mammalian speciation. Compared with
      XB, the XA gene is truncated at its 5' end and bears a 121-bp intragenic deletion
      causing a frameshift and premature translational stop signal. Nevertheless, XA is
      transcribed into a stable 2.6-kb polyadenylated RNA that is expressed uniquely in
      the adrenal gland.

PMID- 1373809
TI  - Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha
      subunit gene is regulated by a gonadotrope-specific protein.
AB  - The molecular mechanisms for the development of multiple distinct endocrine cell
      types in the anterior pituitary have been an area of intensive investigation.
      Though the homeodomain protein Pit-1/GHF-1 is known to be involved in
      differentiation of the somatotrope and lactotrope lineages, which produce growth
      hormone and prolactin, respectively, little is known of the transcriptional
      regulators important for the gonadotrope cell lineage, which produces the
      glycoprotein hormones luteinizing hormone and follicle-stimulating hormone. Using
      transgenic mice and transfection into a novel gonadotrope lineage cell line, we
      have identified a regulatory element that confers gonadotrope-specific expression
      to the glycoprotein hormone alpha-subunit gene. A tissue-specific factor that
      binds to this element is purified and characterized as a 54-kDa protein which is
      present uniquely in cells of the gonadotrope lineage and is not Pit-1/GHF-1. The
      human and equine alpha-subunit genes are also expressed in placental cells.
      However, the previously characterized placental transcription factors designated
      TSEB and alpha-ACT are not found in the pituitary gonadotrope cells, indicating
      that independent mechanisms confer expression of these genes in the two different
      tissues.

PMID- 1373811
TI  - Altered chromosome 6 in immortal human fibroblasts.
AB  - Human diploid fibroblasts have a limited life span in vitro, and spontaneous
      immortalization is an extremely rare event. We have used transformation of human
      diploid fibroblasts by an origin-defective simian virus 40 genome to develop
      series of genetically matched immortal cell lines to analyze immortalization.
      Comparison of a preimmortal transformant (SVtsA/HF-A) with its uncloned and
      cloned immortalized derivatives (AR5 and HAL) has failed to reveal any major
      alteration involving the simian virus 40 genome. Karyotypic analysis, however,
      demonstrated that all of the immortal cell lines in this series have alterations
      of chromosome 6 involving loss of the portion distal to 6q21. The karyotypic
      analysis was corroborated by DNA analyses. Southern analysis demonstrated that
      only one copy of three proto-oncogene loci (ros1, c-myb, and mas1) on 6q was
      retained in immortal cells. Polymerase chain reaction analysis of the
      microsatellite polymorphism at 6q22 (D6S87) showed loss of heterozygosity. In
      addition, elevated expression of c-myb (6q22-23) was observed. We hypothesize
      that the region at and/or distal to 6q21 plays a role in immortalization,
      consistent with the presence of a growth suppressor gene.

PMID- 1373810
TI  - Selective translational control and nonspecific posttranscriptional regulation of
      ribosomal protein gene expression during development and regeneration of rat
      liver.
AB  - Mammalian liver development is accompanied by a transition from rapid growth in
      the fetus to a quiescent state in the adult. However, extensive proliferation can
      be induced in the adult liver by partial hepatectomy. In this study, we examined
      the regulation of ribosomal protein (rp) gene expression in the developing and
      regenerating rat liver. Our results indicate that the translation of rp mRNAs is
      selectively repressed by about 70% upon development from fetal to adult life, as
      illustrated by the decrease in ribosomal loading. In addition, the relative
      abundance of these mRNAs, like that of several other, but not all, housekeeping
      mRNAs, declines during development through a posttranscriptional mechanism. When
      liver cells commence growth following partial hepatectomy, translation of rp
      mRNAs is resumed to near-maximal capacity, as judged by their very efficient
      recruitment into polysomes. The concomitant increase in the abundance rp mRNAs
      under these circumstances is achieved by a posttranscriptional mechanism. The
      apparent fluctuations in the translation efficiency of rp mRNAs are accompanied
      by parallel changes in the expression of the genes encoding the initiation
      factors eIF-4E and eIF-4A. Our results indicate that selective translational
      control of rp mRNAs in mammals is not confined to manipulated cells in culture
      but constitutes an important regulatory mechanism operating in vivo in the course
      of liver development and regeneration.

PMID- 1373812
TI  - Synergistic action of interleukin-6 and glucocorticoids is mediated by the
      interleukin-6 response element of the rat alpha 2 macroglobulin gene.
AB  - One class of genes coding for the acute-phase proteins (acute-phase genes) is
      induced by interleukin 6 (IL-6) through the human transcription factor NF-IL-6
      and its rat homolog IL-6-DBP/LAP. A second class, represented by the rat alpha 2
      macroglobulin gene, utilizes a different IL-6 response element (IL-6-RE) and
      different DNA-binding proteins interacting with this element, the so-called IL-6
      RE binding proteins (IL-6 RE-BPs). Human Hep3B and HepG2 hepatoma, U266 myeloma,
      and CESS lymphoblastoid cells contain IL-6 RE-BPs that form complexes, with the
      IL-6-RE, with gel mobilities indistinguishable from those of the corresponding
      complexes of rat liver cells. The ability to form these complexes was induced by
      IL-6 in human hepatoma cells with a maximum reached after 4 h and required
      ongoing protein synthesis. Multiple copies of an 18-bp element containing the IL
      6-RE core were sufficient to confer both induction by IL-6 and a synergistic
      induction by IL-6 plus glucocorticoids to minimal promoters. The synergism was
      blocked by the receptor antagonist RU486 and thus was dependent on the
      glucocorticoid receptor (GR). However, the 18-bp element contained no consensus
      GR-binding site, and recombinant GR did not bind at this sequence. Therefore, the
      synergism was probably achieved by an indirect effect of a glucocorticoid
      activated intermediate gene on the IL-6 RE-BPs. The rat IL-6 RE-BP had a
      molecular weight of 102 +/- 10 kDa and was thus distinct from NF-IL-6 and IL-6
      DBP/LAP. Therefore, IL-6 must activate two different classes of liver acute-phase
      genes through at least two different nuclear DNA-binding proteins: NF-IL-6/IL-6
      DBP/LAP and the IL-6 RE-BP.

PMID- 1373813
TI  - Different sequence elements are required for function of the cauliflower mosaic
      virus polyadenylation site in Saccharomyces cerevisiae compared with in plants.
AB  - We show that the polyadenylation site derived from the plant cauliflower mosaic
      virus (CaMV) is specifically functional in the yeast Saccharomyces cerevisiae.
      The mRNA 3' endpoints were mapped at the same position in yeast cells as in
      plants, and the CaMV polyadenylation site was recognized in an orientation
      dependent manner. Mutational analysis of the CaMV 3'-end-formation signal
      revealed that multiple elements are essential for proper activity in yeast cells,
      including two upstream elements that are situated more than 100 and 43 to 51
      nucleotides upstream of the poly(A) addition site and the sequences at or near
      the poly(A) addition site. A comparison of the sequence elements that are
      essential for proper function of the CaMV signal in yeast cells and plants showed
      that both organisms require a distal and a proximal upstream element but that
      these sequence elements are not identical in yeast cells and plants. The key
      element for functioning of the CaMV signal in yeast cells is the sequence
      TAGTATGTA, which is similar to a sequence previously proposed to act in yeast
      cells as a bipartite signal, namely, TAG ... TATGTA. Deletion of this sequence in
      the CaMV polyadenylation signal abolished 3'-end formation in yeast cells, and a
      single point mutation in this motif reduced the activity of the CaMV signal to
      below 15%. These results indicate that the bipartite sequence element acts as a
      signal for 3'-end formation in yeast cells but only together with other cis
      acting elements.

PMID- 1373814
TI  - Macrophage growth arrest by cyclic AMP defines a distinct checkpoint in the mid
      G1 stage of the cell cycle and overrides constitutive c-myc expression.
AB  - Proliferation of a murine macrophage cell line (BAC1.2F5) in response to colony
      stimulating factor 1 (CSF-1) is inhibited by prostaglandin E2 (PGE2)-mediated
      elevation of intracellular cyclic AMP (cAMP). When BAC1.2F5 cells were growth
      arrested in early G1 by CSF-1 starvation and stimulated to synchronously enter
      the cell cycle by readdition of growth factor, PGE2 inhibited [3H]thymidine
      incorporation when added before mid-G1, but its addition at later times did not
      block the onset of S phase. Reversible cell cycle arrest mediated by a cAMP
      analog required the presence of CSF-1 for cells to initiate DNA synthesis,
      whereas cells released from an aphidicolin block at the G1/S boundary entered S
      phase in the absence of CSF-1. PGE2 or cAMP analogs did not block the initial
      induction of c-myc mRNA by CSF-1 but abolished the CSF-1-dependent expression of
      c-myc mRNA in the mid-G1 stage of the cell cycle. The cAMP-mediated reduction in
      c-myc RNA levels was due to decreased c-myc transcription. However, CSF-1
      dependent BAC1.2F5 clones infected with a c-myc retrovirus were growth arrested
      by cAMP analogs despite constitutive c-myc expression. Therefore, the reduction
      of endogenous c-myc expression by cAMP is neither necessary nor sufficient for
      growth inhibition.

PMID- 1373815
TI  - Structure and expression of a calcium-binding protein gene contained within a
      calmodulin-regulated protein kinase gene.
AB  - We have determined the first genomic structure and characterized the mRNA and
      protein products of a novel vertebrate gene that encodes a calcium-binding
      protein with amino acid sequence identity to a protein kinase domain. The
      elucidation of the complete DNA sequence of this transcription unit and adjacent
      genomic DNA, Southern blot and polymerase chain reaction analyses of cellular
      genomic DNA, and examination of mRNA and protein species revealed that the
      calcium-binding kinase-related protein (KRP)-encoding gene is contained within
      the gene for a calmodulin-regulated protein kinase, myosin light-chain kinase
      (MLCK). The KRP gene transcription unit is composed of three exons and a 5'
      flanking sequence containing a canonical TATA box motif. The TATA box, the
      transcription initiation site, and the first 109 nucleotides of the 5' noncoding
      region of the KRP mRNA correspond to an MLCK gene intron sequence. Both KRP and
      MLCK are produced in the same adult chicken tissue in relatively high abundance
      from a single contiguous stretch of genomic DNA and utilize the same reading
      frame and common exons to produce distinct mRNAs (2.7 and 5.5 kb, respectively)
      that encode proteins with dissimilar biochemical functions. There appears to be
      no precedent in vertebrate molecular biology for such a relationship. This may
      represent a mechanism whereby functional diversity can be achieved within the
      same vertebrate tissue by use of common exons to produce shuffled domains with
      identical amino acid sequences in different molecular contexts.

PMID- 1373818
TI  - Sexual dimorphism and growth hormone regulation of a hybrid gene in transgenic
      mice.
AB  - The sexually dimorphic expression of the urinary protein genes of mice (Mup
      genes) in the liver is mediated by the different male and female temporal
      patterns of circulating GH. Normal females were induced to male levels when GH
      was administered by injection to mimic the male GH pattern, showing that
      expression at the male level does not require a male sex steroid status in
      addition to intermittent GH. Two Mup-alpha 2u-globulin hybrid transgenes with
      different Mup gene promoters showed sexually dimorphic expression, and their
      expression in females increased to male levels upon testosterone treatment. GH
      deficient (lit/lit) mice did not express these transgenes, and GH-deficient
      females did not respond to testosterone treatment, showing that GH was required
      for induction. Both normal and GH-deficient females were induced to male levels
      when GH was administered by injection. This is the first report of a transgene
      responsive to GH. A transgene consisting of a Mup promoter fused to a Herpes
      simplex virus thymidine kinase reporter sequence also showed sexual dimorphism,
      although to a lesser degree. It was expressed at the same level in normal females
      and GH-deficient mice of both sexes and was induced when GH-deficient mice were
      treated with GH. We propose that this transgene has a basal constitutive
      expression, possibly due to the absence of any rodent DNA downstream of the
      promoter. Since expression of the transgene was significantly induced by GH, the
      GH response is due at least in part to sequences in the promoter region.

PMID- 1373816
TI  - Characterization of hematopoietic intracellular protein tyrosine phosphatases:
      description of a phosphatase containing an SH2 domain and another enriched in
      proline-, glutamic acid-, serine-, and threonine-rich sequences.
AB  - Protein tyrosine phosphatases (PTPases) are a family of enzymes important in
      cellular regulation. Characterization of two cDNAs encoding intracellular PTPases
      expressed primarily in hematopoietic tissues and cell lines has revealed proteins
      that are potential regulators of signal transduction. One of these, SHP (Src
      homology region 2 [SH2]-domain phosphatase), possesses two tandem SH2 domains at
      the amino terminus of the molecule. SH2 domains have previously been described in
      proteins implicated in signal transduction, and SHP may be one of a family of
      nonreceptor PTPases that can act as direct antagonists to the nonreceptor protein
      tyrosine kinases. The SH2 domains of SHP preferentially bind a 15,000-Mr protein
      expressed by LSTRA cells. LSTRA cells were shown to express SHP protein by
      immunoprecipitation, thus demonstrating a potential physiological interaction.
      The other PTPase, PEP (proline-, glutamic acid-, serine-, and threonine-rich
      [PEST]-domain phosphatase), is distinguished by virtue of a large carboxy
      terminal domain of approximately 500 amino acids that is rich in PEST residues.
      PEST sequences are found in proteins that are rapidly degraded. Both proteins
      have been expressed by in vitro transcription and translation and in bacterial
      expression systems, and both have been demonstrated to have PTPase activity.
      These two additional members of the PTPase family accentuate the variety of
      PTPase structures and indicate the potential diversity of function for
      intracellular tyrosine phosphatases.

PMID- 1373817
TI  - Differential regulation of the Wnt gene family during pregnancy and lactation
      suggests a role in postnatal development of the mammary gland.
AB  - The mouse Wnt family comprises at least 10 members sharing substantial amino acid
      identity with the secreted glycoprotein Wnt-1/int-1. Two of these, Wnt-1 and Wnt
      3, are implicated in mouse mammary tumor virus-associated adenocarcinomas,
      although neither member is normally expressed in the mammary gland. These results
      suggest the presence of active cellular pathways which mediate the action of Wnt
      1 and Wnt-3 signals. An understanding of the normal role of these signalling
      pathways is clearly necessary to comprehend the involvement of Wnt-1 and Wnt-3 in
      mammary tumorigenesis. We demonstrate here that five Wnt family members are
      expressed and differentially regulated in the normal mouse mammary gland. In
      addition, some of these genes are also expressed in both Wnt-1-responsive and
      nonresponsive mammary epithelial cell lines. We propose that Wnt-mediated
      signalling is involved in normal regulation of mammary development and that
      inappropriate expression of Wnt-1, Wnt-3, and possibly other family members can
      interfere with these signalling pathways.

PMID- 1373820
TI  - The gene encoding hypoxanthine-guanine phosphoribosyltransferase as target for
      mutational analysis: PCR cloning and sequencing of the cDNA from the rat.
AB  - In this paper, the cloning and nucleotide sequence of the cDNA of the rat gene
      coding for hypoxanthine-guanine phosphoribosyltransferase (hprt) is reported.
      Knowledge of the cDNA sequence is needed, among other reasons, for the molecular
      analysis of hprt mutations occurring in rat cells, such as skin fibroblasts
      isolated according to the granuloma pouch assay. The rat hprt cDNA was
      synthesized and used as a template for in vitro amplification by PCR. For this
      purpose, oligonucleotide primers were used, the nucleotide sequences of which
      were based on mouse and hamster hprt cDNA sequences. Sequence analysis of 1146 bp
      of the amplified rat hprt cDNA showed a single open reading frame of 654 bp,
      encoding a protein of 218 amino acids. In the predicted rat hprt amino acid
      sequence, the proposed functional domains for 5'-phosphoribosyl-1-pyrophosphate
      (PRPP) and nucleotide binding in phosphoribosylating enzymes as well as a region
      near the carboxyl terminal part were highly conserved when compared with amino
      acid sequences of other mammalian hprt proteins. Analysis of hprt amino acid
      sequences of 727 independent hprt mutants from human, mouse, hamster and rat
      cells bearing single amino acid substitutions revealed that a large variety of
      amino acid changes were located in these highly conserved regions, suggesting
      that all 3 domains are important for proper catalytic activity. The suitability
      of the hprt gene as target for mutational analysis is demonstrated by the fact
      that amino acid changes in at least 151 of the 218 amino acid residues of the
      hprt protein result in a 6-thioguanine-resistant phenotype.

PMID- 1373819
TI  - Differential regulation of apolipoprotein-E messenger RNA in zona fasciculata
      cells of rat adrenal gland determined by in situ hybridization.
AB  - Previous studies showed that apolipoprotein-E (apoE) mRNA is regulated in rat
      adrenal gland by treatments that alter adrenal gland cholesterol content and
      steroidogenesis. In the present study cell types expressing apoE mRNA were
      determined by in situ hybridizations using an [alpha-35S]UTP-labeled RNA probe.
      Autoradiographic grains were counted to compare apoE expression in adrenal glands
      from control and experimentally treated animals. In control adrenal gland, zona
      (z.) fasciculata and z. reticularis exhibited the highest level of apoE mRNA
      expression, with lower levels in z. glomerulosa and medulla. Dexamethasone (DEX)
      treatment selectively increased apoE mRNA 3-fold in outer z. fasciculata, but not
      in other adrenal zones. ApoE mRNA expression appeared to be lower in adrenal
      glands from 4-aminopyrazolopyrimidine-treated rats, in that differences among
      adrenal gland zones were abolished. DEX treatment increased adrenal gland
      cholesteryl ester and oil red O staining in z. fasciculata cells in which the
      apoE mRNA concentration was increased as well as in other cortical cells in which
      apoE mRNA was unchanged. Aminoglutethimide administration led to a large increase
      in oil red O staining throughout the cortex, including z. fasciculata, without
      affecting apoE mRNA expression. These data suggest that adrenal gland apoE mRNA
      expression is not closely coupled to cellular cholesterol concentrations.
      Increased apoE mRNA expression in z. fasciculata of DEX-treated animals suggests
      an inverse relationship between apoE mRNA concentration and the level of
      steroidogenesis. This result is consistent with the proposal that apoE may play a
      role in regulating the utilization of cholesterol for steroid production.

PMID- 1373821
TI  - The induction of mitotic chromosome malsegregation in Aspergillus nidulans.
      Quantitative structure activity relationship (OSAR) analysis with chlorinated
      aliphatic hydrocarbons.
AB  - The biological activity of 24 chlorinated aliphatic hydrocarbons has been studied
      in the mold Aspergillus nidulans. The ability to induce chromosome
      malsegregation, lethality and mitotic growth arrest has been experimentally
      determined for each chemical. These data, together with those of 11 related
      compounds previously investigated, generated a data base which was used for
      quantitative structure-activity relationship (QSAR) analysis. To this aim, both
      physico-chemical descriptors and electronic parameters of each compound have been
      calculated and included in the analysis. The QSAR analysis indicated that toxic
      effects induced by chlorinated aliphatics in A. nidulans are mainly dependent on
      steric factors, as indicated by the correlation with molar refractivity (MR).
      Conversely, the ease with which they accept electrons, parametrized by LUMO
      (energy of the lowest unoccupied molecular orbital), plays a prevailing role in
      determining the aneuploidizing properties. An involvement of free radicals,
      generated by the reductive metabolism of haloalkanes, is hypothesized as an
      explanation of the data.

PMID- 1373822
TI  - On spontaneous mutagenesis and cell cultivation conditions.
AB  - The leu2 revertant content of a Saccharomyces cerevisiae cell culture increases
      as the leucine concentration in the nutrient solid medium decreases. Reversions
      form in the S-phase of the cell cycle. If a cell culture from a medium with a low
      concentration of leucine containing the revertants which have just formed is
      transferred on a medium with a normal or higher than normal leucine content,
      these 'newborn' revertants disappear at the end of the G1-phase or at the
      beginning of the S-phase of the next cell cycle. These data can be explained
      either by a difference in the ability of revertants formed in the culture to
      compete with the cells of the initial strain on different media, or on the basis
      of the intermediate heteroduplex model proposed by F.W. Stahl (1988).

PMID- 1373823
TI  - Griseofulvin-induced aneuploidy and meiotic delay in female mouse germ cells. I.
      Cytogenetic analysis of metaphase II oocytes.
AB  - Griseofulvin (GF) was tested in female mouse germ cells for the induction of
      aneuploidy and meiotic arrest. Superovulated mice were orally treated with 200,
      666, 1332 or 2000 mg/kg in olive oil at the time of human chorionic gonadotrophin
      (HCG) injection and were sacrificed 18 h later. A dose-dependent increase in the
      frequency of metaphase I (M I) arrested oocytes was observed (maximum of 70%).
      Aneuploidy was not significantly induced. Also, the kinetics of meiotic
      progression up to the metaphase II (M II) stage was studied in untreated mice in
      order to correlate the time of treatment with the time of the first meiotic
      division. The results demonstrate that the majority of cells was treated with GF
      approximately 8 h before the M I stage. A second series of experiments were
      performed to test GF effects at a different treatment time. Doses of 200, 666 or
      2000 mg/kg were administered 2 h post HCG. As in the first series of experiments,
      the animals were sacrificed 18 h post HCG. The results, compared with those
      obtained in the first experimental series, showed an inverse trend for meiotic
      arrest and aneuploidy induction. The frequency of M I arrested oocytes dropped
      from a maximum of 70% to a maximum of 20%, while, at the latest treatment time, a
      dose-dependent increase in the frequency of hyperploid oocytes was observed up to
      56% aberrant cells at 2000 mg/kg. Altogether the results suggest that the arrest
      of meiotic division and the induction of aneuploidy by GF are caused by
      interaction with different targets or different developmental stages of the same
      target. In conclusion, GF has been shown to induce aneuploidy during the first
      meiotic division in a dose-related manner, together with other effects such as
      polyploidy, developmental delay and meiotic arrest. Also, these findings
      demonstrate that the sensitivity of the oocyte target(s) may be restricted to a
      specific time period and that a correct experimental protocol is critical for
      assessing the aneugenic activity of a chemical.

PMID- 1373824
TI  - Griseofulvin-induced aneuploidy and meiotic delay in female mouse germ cells. II.
      Cytogenetic analysis of one-cell zygotes.
AB  - The effects of griseofulvin (GF) upon the first meiotic division of female mouse
      germ cells were evaluated by cytogenetic analysis of first-cleavage (1-Cl)
      zygotes. The present study is an extension of an investigation that began with
      the cytogenetic analysis of metaphase II (M II) oocytes. Different doses (200,
      666, 1332, 2000 mg/kg) were tested by oral administration of GF to superovulated
      animals either at the time of human chorionic gonadotrophin (HCG) injection or 2
      h post HCG. When GF was given at the time of HCG, significant dose-dependent
      increases of different types of cytogenetically abnormal cells were found. These
      included zygotes containing ostensibly female-derived M I or M II arrested
      chromosomes and polyploid zygotes. The total yields of these aberrations were
      2.9, 4.3, 26.2, 60.6, and 64.1% for control, 200, 666, 1332, and 2000 mg/kg,
      respectively. The origin of these zygotes was attributed to the fertilization of
      oocytes that had been previously arrested at M I. No significant induction of
      hyperploidy was detected. Developmentally abnormal zygotes were still observed
      when GF was administered 2 h post HCG, although their frequencies were
      significantly lower than in the first series of experiments. The yields of
      developmentally abnormal zygotes were 49, 10.2, and 23.6% at 200, 666, and 2000
      mg/kg. Additionally, a dose-dependent increase in the frequency of hyperploid
      zygotes was detected up to a maximum of 36.5% at 2000 mg/kg. These results
      confirm the cytogenetic observations from M II oocytes after GF treatment under
      the same experimental conditions; namely, a dramatic change in the oocyte target
      susceptibility to GF occurred within a short time period. Also, the present study
      demonstrated that most of GF-induced aneuploid oocytes were fertilized and
      reached first-cleavage metaphase.

PMID- 1373825
TI  - Molecular mechanisms of the formation of DNA double-strand breaks and induction
      of genomic rearrangements.
AB  - The probability that damage occurs in closely opposed sites on complementary DNA
      strands increases when DNA is heavily modified with mutagenic agents. Enzymatic
      excision of the opposite lesions produces DNA double-strand breaks which give
      rise to genomic rearrangements (deletions, insertions, etc.). Plasmid systems
      were developed for studying chemical lesions leading to double-strand breaks and
      the fate of broken plasmid molecules within bacterial cells. Deletions result
      from the base-pairing of fortuitously located direct repeats flanking the DNA
      broken ends; as a consequence, the latter are joined, while the DNA fragment
      between the direct repeats is deleted. Genomic rearrangements arise during the
      repair of the DNA double-strand breaks, and both events are due to similar repair
      enzymes which maintain the integrity of the DNA primary structure when conditions
      are not stressful. A number of genomic rearrangements and point mutations seem to
      be predetermined by the DNA primary structure.

PMID- 1373826
TI  - Combined mutagenicity of methyl methanesulfonate and ethyl methanesulfonate in
      Chinese hamster V79 cells.
AB  - The combined effects of methyl methanesulfonate (MMS) and ethyl methanesulfonate
      (EMS) on the induction of 6-thioguanine (6TG)-resistant mutants and chromosome
      aberrations were examined in Chinese hamster V79 cells. Cells were simultaneously
      treated with EMS at a concentration of D20 and MMS at various concentrations for
      3, 6 or 9 h. In other experiments cells were simultaneously treated with MMS at a
      concentration of D20 and EMS at various concentrations for 3, 6 or 9 h. The
      mathematical analysis of the combined effects of both chemicals for cell killing
      (cytotoxicity) and 6TG-resistant mutations indicates that synergistic
      interactions were observed for both cell killing and mutations induced by MMS and
      EMS. The frequency of chromosome aberrations induced by simultaneous treatment
      with MMS at a concentration of D20 and EMS at various concentrations for 3 h was
      additive. However, the frequency of chromosome aberrations induced by EMS at a
      concentration of D20 and MMS at various concentrations for 3 h was not
      significantly different from those induced by MMS alone.

PMID- 1373827
TI  - Structural and electronic properties of MX compounds related to TA100
      mutagenicity. A semi-empirical molecular orbital QSAR study.
AB  - The structural and electronic properties of chlorofuranones including MX and its
      anhydride were calculated using the semi-empirical AM1 method to elucidate the
      key features related to the strong mutagenic activity of MX. Significant
      correlations were found between Ames TA100 mutagenicity and the following
      electronic parameters of chlorofuranones: LUMO energy (r = 0.9607, n = 17),
      electron affinity (r = 0.9557), LUMO electron density at the alpha-carbon (r =
      0.8855) and partial charge of the alpha-carbon (r = 0.8812). Based on these
      results, a molecular orbital QSAR model for the mutagenic activity of 17 MX
      analogues is presented. The controversial role of the open-chain tautomers of MX
      compounds, chlorinated butenoic acids, is discussed briefly.

PMID- 1373828
TI  - In vivo human somatic mutation: frequency and spectrum with age.
AB  - The number and molecular nature of in vivo mutations in relation to age was
      studied at the autosomal HLA-A locus in human lymphocytes. Mutant lymphocytes
      were isolated by immunoselection, cloned at limiting dilution and enumerated, and
      the HLA-A gene and other polymorphic gene loci on chromosome 6 were studied by
      Southern blotting to determine gene dosage and loss of heterozygosity. Results of
      167 assays in 73 individuals showed that the total number of mutant lymphocytes
      increased significantly with age from a geometric mean frequency of 0.71 x 10(-5)
      in neonates to 6.53 x 10(-5) in elderly individuals. Analysis of rearrangement of
      T lymphocyte receptor beta or gamma chain genes gave a best estimate of 3.3% for
      the proportion of mutant lymphocytes detected which are clonally related.
      Molecular study of 434 mutants from 31 individuals showed no change on Southern
      blotting in 64.7%, gene deletion in 2.8% and mitotic recombination in 32.5%. Two
      mutants due to gene conversion but no mutants due to non-disjunction were
      detected. The number of 'no change' and recombination mutants increased
      significantly with age. There was a significant difference between individuals in
      the proportion of mutants which resulted from mitotic recombination and the data
      suggested that the proportion was bimodally distributed. The point of crossing
      over in recombination mutants was predominantly randomly distributed between the
      HLA-A locus and the centromere.

PMID- 1373829
TI  - The genotoxicity of chromium(VI) oxide in the wing spot test of Drosophila
      melanogaster is over 90% due to mitotic recombination.
AB  - Chromium(VI) oxide and chromium(III) chloride were tested in the wing somatic
      mutation and recombination test (SMART) in Drosophila melanogaster according to
      standard procedures. The hexavalent compound was highly genotoxic in both chronic
      and acute treatments whereas the trivalent one was clearly negative. Further
      analysis of wings carrying an inversion chromosome which eliminates all
      recombination events showed that over 90% of the spots induced by chromium(VI)
      oxide are due to mitotic recombination.

PMID- 1373830
TI  - Bio-antimutagenic activities of vitamin B6 in E. coli and mouse peripheral blood
      cells.
AB  - Pyridoxal (PL) and pyridoxal 5'-phosphate (PLP) showed a marked bio-antimutagenic
      effect on UV-induced mutagenesis in E. coli B/r WP2, but not in the DNA excision
      repair-deficient strain WP2suvrA under the condition where no cellular toxicity
      was observed. No delay in the first cell division was seen on post-treatment with
      PL after UV irradiation. PL reduced not only UV- but 4-nitroquinoline-1-oxide
      induced mutation, while it was ineffective in N-methyl-N'-nitro-N
      nitrosoguanidine- or gamma-ray-treated cells. These results suggest that PL
      promotes DNA excision repair directly or indirectly and the decrease in the
      amount of unrepaired DNA damage might cause the reduction of UV-induced mutations
      in E. coli B/r WP2. In addition to the above observation, PLP reduced the
      frequency of mitomycin C- (2 mg/kg, i.p.) induced micronuclei in mouse peripheral
      blood cells. Simultaneous or subsequent oral administration of PLP (25 mg/kg)
      decreased the frequency of micronucleated peripheral reticulocytes.

PMID- 1373831
TI  - A comparative study of the potentiating effect of caffeine and poly-D-lysine on
      chromosome damage induced by X-rays in plant cells.
AB  - X-Ray-induced chromosomal aberrations (CA) were potentiated by post-treatments in
      G2 with either caffeine (caff) or poly-D-lysine (PDL) in root-tip cells of Allium
      cepa. The enhancement of the yield of CA was concomitant with an increase in the
      frequency of mitosis. Our results seem to support the idea of a direct
      relationship between radiation-induced G2 delay and repair of chromosome damage.
      Here we report on similarities between caffeine and PDL in both decreasing G2
      delay and enhancing chromatid aberration yield. The possible molecular
      mechanism(s) of action responsible for the cytogenetic effects observed are
      discussed.

PMID- 1373832
TI  - A mutational hotspot in the aprt gene of Chinese hamster cells.
AB  - Early work with adenine phosphoribosyltransferase-deficient mutants of CHO cells
      suggested that a site existed in the third exon of this gene which was
      preferentially susceptible to mutation by ethyl methanesulphonate. To determine
      whether this was real we analysed a large collection of induced mutants, and
      generated a high-density mutational spectrum for this exon. In addition, 4 sites
      outside exon 3 were analysed by blot. 37 mutations were found in 19 available
      sites, six of which were at nucleotide 1365, 1 of 2 sites in the putative hotspot
      (P less than 0.02). One other site, 1308, also was mutated in 6 cell lines and
      may also be preferentially mutable.

PMID- 1373833
TI  - Chromosomal changes in Chinese hamster AA8 cells caused by podophyllin, a common
      treatment for genital warts.
AB  - Podophyllin, a plant derivative of variable composition, is used widely within
      New Zealand as a treatment for genital warts. One local source of podophyllin has
      been tested for ability to cause mutagenic effects in Salmonella typhimurium as
      well as for effects on chromosomes of Chinese hamster AA8 cells. Although only
      weakly mutagenic in one strain of Salmonella, podophyllin caused structural
      aberrations as well as changes in chromosome number in the Chinese hamster cells.
      The range of aberrations was similar to those caused by teniposide, a close
      structural relative of the major component, which was used as a positive control
      in the Chinese hamster cell experiments. A literature review revealed that
      podophyllin was shown to cause changes of chromosome number in the mouse cervix
      in vivo, although aberrations were not studied. Patients treated with podophyllin
      will usually possess one form of the papilloma virus, and this itself may have
      some oncogenic potential. We suggest that podophyllin could potentiate these
      effects and question its continued widespread use.

PMID- 1373834
TI  - Mutational activation of H-ras oncogene transformability by alkylnitrosourea
      induced DNA damage.
AB  - To assess the role of DNA alkylation damage in oncogene activation, plasmid DNA
      containing H-ras proto-oncogene (p220-EC) and oncogene (p220-EJ) were treated
      with increasing concentrations of carcinogenic methylnitrosourea (MNU) and
      ethylnitrosourea (ENU). The modified plasmid DNA were analyzed by transfection
      transformation of the NIH/3T3-recipient cells. Treatment with varying doses of
      MNU (0.1-5 mM) and ENU (1-15 mM) did not result in the inactivation of the
      plasmid containing target genes. A transformation efficiency of greater than 40%
      was observed upon treatment of H-ras oncogene with the highest doses of the
      alkylating agents. The morphologically transformed foci obtained with alkylated
      p220-EC ranged from 2.8 to 0.3/microgram MNU alkylated and 1.6 to 0.6/microgram
      ENU alkylated plasmid DNA. A significant proportion of the morphological
      transformants exhibited growth in soft agar. The HpaII/MspI restriction length
      polymorphism (RFLP) at codon 12 of H-ras exon-1 was detected with 4 independently
      isolated clones obtained from MNU-alkylated p220-EC transfections. Allele
      specific in situ gel hybridization with a battery of codon 12 and codon 61
      oligonucleotide probes confirmed these RFLPs to be due to sequence changes at
      codon 12. No clone with sequence changes in the H-ras codon 61 could be detected.
      The data indicate that a high degree of in vitro alkylation damage of the target
      gene is necessary to elicit mutational activation of H-ras in transfection
      transformation assay. Low frequency notwithstanding, the data demonstrate that
      DNA alkylation damage at critical target sites can initiate neoplastic cellular
      transformation.

PMID- 1373835
TI  - Predictive assay for rodent carcinogenicity using in vivo biochemical parameters:
      operational characteristics and complementarity.
AB  - 111 chemicals of known rodent carcinogenicity (49 carcinogens, 62
      noncarcinogens), including many promoters of carcinogenesis, nongenotoxic
      carcinogens, hepatocarcinogens, and halogenated hydrocarbons, were selected for
      study. The chemicals were administered by gavage in two dose levels to female
      Sprague-Dawley rats. The effects of these 111 chemicals on 4 biochemical assays
      (hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase
      activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic
      cytochrome P-450 content (P450)) were determined. Composite parameters are
      defined as follows: CP = [ODC and P450), CT = [ALT and ODC), and TS = [DD or CP
      or CT]. The operational characteristics of TS for predicting rodent cancer were
      sensitivity 55%, specificity 87%, positive predictivity 77%, negative
      predictivity 71%, and concordance 73%. For these chemicals, the 73% concordance
      of this study was superior to the concordance obtained from published data from
      other laboratories on the Ames test (53%), structural alerts (SA) (46%),
      chromosome aberrations in Chinese hamster ovary cells (ABS) (48%), cell mutation
      in mouse lymphoma 15178Y cells (MOLY) (52%), and sister-chromatid exchange in
      Chinese hamster ovary cells (SCE) (60%). The 4 in vivo biochemical assays were
      complementary to each other. The composite parameter TS also shows
      complementarity to all 5 other predictors of rodent cancer examined in this
      paper. For example, the Ames test alone has a concordance of only 53%. In
      combination with TS, the concordance is increased to 62% (Ames or TS) or to 63%
      (Ames and TS). For the 67 chemicals with data available for SA, the concordance
      for predicting rodent carcinogenicity was 47% (for SA alone), 54% (for SA or TS),
      and 66% (for SA and TS). These biochemical assays will be useful: (1) to predict
      rodent carcinogenicity per se, (2) to 'confirm' the results of short-term
      mutagenicity tests by the high specificity mode of the biochemical assays (the
      specificity and positive predictivity are both 100%), and (3) to be a component
      of future complementary batteries of tests for predicting rodent carcinogenicity.

PMID- 1373836
TI  - Responsiveness of tumorigenic and non-tumorigenic CHEF18 Chinese hamster cells to
      1-beta-D-arabinofuranosylcytosine treatment.
AB  - In cultured mammalian cells, sister chromatid exchanges are easily induced by
      agents that perturb the scheduled timing of DNA replication. In this work a
      blockage of DNA synthesis induced by 1-beta-D-arabinofuranosylcytosine was
      applied to non-tumorigenic and tumorigenic CHEF18 Chinese hamster cells, and
      their responsiveness was compared. The data show that both the induction of
      sister chromatid exchanges and the reduction of the colony-forming ability were
      less extensive in non-tumorigenic than in tumorigenic CHEF18 cells. The results
      suggest that a tight control of the scheduled timing of DNA replication is
      present in non-tumorigenic CHEF18 cells and perhaps this feature avoids the
      generation of those chromosomal structures that are responsible for the abnormal
      induction of sister chromatid exchanges and for the elevated cytotoxicity seen in
      tumorigenic cells.

PMID- 1373837
TI  - The biological activity of hydrogen peroxide. V. The crystal structure of a
      histidine-peroxide adduct and its biological activities.
AB  - Crystals were prepared from a mixture of L-histidine (L-His) and hydrogen
      peroxide (H2O2) and tested for biological activity in human embryonic
      fibroblasts. The crystal structure was determined by X-ray diffraction to be that
      of an adduct, in which the H2O2 molecule forms a OH-N hydrogen bond with N delta
      of the side chain of L-His. A 10-min treatment with this adduct in solution (25
      150 microM) induced more marked chromosomal aberrations and more single-strand
      breaks (SSB) in DNA than H2O2 itself, and these effects were generated in a dose
      dependent manner. With respect to the induction of dicentric and ring chromosomes
      (Dic and Ring), a maximum frequency of 1.3 per cell was obtained at 75 microM.
      This maximum level of induction by the adduct was 6-7 times higher than that by
      H2O2 and was comparable to that by the mixture of L-His and H2O2 which we
      observed in our previous studies. The most effective dose for such induction by
      the adduct was also similar to that of L-His in the mixture. Cell growth was
      inhibited more strongly by the adduct than by H2O2 alone after a 60-min treatment
      at 75 microM, although there was not much difference between their effects after
      a 10-min treatment at 75 microM. The reactive factors derived from the adduct
      were the same as those in the mixture, and are suggested to be derivatives of
      H2O2, hydroxyl radicals (.OH) and/or singlet oxygen (1O2). Thus the patterns of
      induction and kinetics of the biological activities of the adduct were very
      similar to those of the mixture, but not to those of H2O2. These results suggest
      that the formation of the adduct plays an important role in the enhancement of
      the expression of the biological activity of H2O2 by the coadministration of L
      His and H2O2, which we observed in our previous study.

PMID- 1373838
TI  - Trichlormethine hydrochloride and correlation of its mutagenic and toxic effects
      on male germ cells in mice.
AB  - The genetic effect of the cytostatic trichlormethine hydrochloride (TS-160 Spofa)
      was assessed after a 1-week administration using the dominant lethal mutation
      test (DLM) and the sperm abnormality test. The dosage was 0.5 mg/kg for 7
      consecutive days, an equivalent of the human therapeutic dosage. Simultaneously,
      the cytostatic's direct toxic effect on male sex organs was assessed. TS-160
      carries a genetic risk for the postmeiotic stages of spermatogenesis (DLM) and is
      responsible for interference in the morphology of sperm heads through its action
      on spermatocytes. The toxic effects of TS-160 were found to influence the body
      weight of mice (days 4-25 after administration), to reduce the relative weight of
      the testes (days 18-25 after administration), to damage spermatogenesis in the
      seminiferous tubules (spermatids), to be responsible for an appearance of
      multinucleate cells in the epididymides, and for an increased rate of abnormality
      of the heads of fully mature spermatozoa. Our findings stress the need to
      separate the cytotoxic effects from genetic effects so as to avoid false
      positives, especially in the test for head abnormalities, and also in the
      assessment of the fertility of male animals or fertilization of females mated
      with treated males.

PMID- 1373839
TI  - Radical-mediated modification of deoxyguanine and deoxyribose by luteoskyrin and
      related anthraquinones.
AB  - When cultured Reuber hepatoma H4-II-E and fibroblast Balb/3T3 cells were exposed
      to various concentrations of 5 derivatives of anthraquinones, luteoskyrin, a bis
      anthraquinoid hepatocarcinogenic mycotoxin, exhibited the highest cytotoxicity to
      these cell lines. The content of 8-hydroxydeoxyguanine residues in the DNA of H4
      II-E cells was dose- and time-dependently increased by luteoskyrin. The
      tumorigenic anthraquinones such as rugulosin and danthron also slightly elevated
      the level of this modified DNA base, while no such modification was observed with
      chrysophanol and emodin. Detailed experiments with luteoskyrin have demonstrated
      the formation of 8-hydroxydeoxyguanine and the degradation of deoxyribose into
      thiobarbituric acid-reactive products in the presence of ascorbic acid. These
      findings suggest the possible involvement of anthraquinone-derived hydroxy
      radicals for the modification of DNA base and deoxyribose.

PMID- 1373840
TI  - Simultaneous evaluation of genotoxicity data from different sources: a
      multivariate statistical approach.
AB  - A great deal of information on short-term mutagenicity assays presently exists,
      having been generated through individual as well as large comparative programs.
      The comparative programs have often examined the same tests, but with different
      sets of chemicals; this then gives rise to the problem of how to identify the
      information which is common to the different data bases, i.e., the general
      properties of the assays. This paper continues previous analyses of this subject,
      and describes a general approach by which different and heterogeneous data bases
      can be compared to each other. The results relative to 4 assays (Salmonella
      typhimurium gene mutation, mouse lymphoma L5178Y cell gene mutation, chromosomal
      aberrations in CHO cells, and SCEs in CHO cells) in 4 different data bases were
      studied. Factor analysis was used to model the different pieces of information.
      The analysis demonstrated a concordance between the indications of the U.S.
      National Toxicology Program and the International Program for the Evaluation of
      Short-Term Tests for Carcinogens, whereas the results of Gene-Tox and the
      International Program for Chemical Safety turned out to be biased, to different
      degrees, by their specific aims and characteristics. Moreover, the general
      properties--independent of the specific data bases--of the 4 assays were
      highlighted, and the similarities between the performances of the assays were
      given a quantitative measure.

PMID- 1373842
TI  - Effects of L-ascorbic acid on the mutagenicity of ethyl methanesulfonate in
      cultured mammalian cells.
AB  - The effects of L-ascorbic acid (AsA) on the mutations induced by ethyl
      methanesulfonate (EMS) were examined by means of the 6-thioguanine (6TG)
      resistant mutation assay and chromosome aberration assay in cultured Chinese
      hamster V79 cells. When cells were treated with EMS at various concentrations in
      the presence of 100 micrograms/ml AsA, EMS-induced 6TG-resistant mutations were
      reduced about one third or one fourth. EMS-induced chromosome aberrations were
      also reduced by AsA. These reductions in the mutagenicity of EMS were also found
      when cells were treated with mixtures of AsA and EMS which had previously been
      incubated at 37.0 degrees C for 2 h. In pre- and post-treatments with AsA,
      however, the frequencies of EMS-induced mutations were not reduced, but rather
      increased markedly.

PMID- 1373841
TI  - Effects of various chemical compounds on spontaneous and hydrogen peroxide
      induced reversion in strain TA104 of Salmonella typhimurium.
AB  - In experiments designed to determine which active oxygen species contribute to
      hydrogen peroxide (HP)-induced reversion in strain TA104 of Salmonella
      typhimurium, 1,10-phenanthroline (an iron chelator, which prevents the formation
      of hydroxyl radicals from HP and DNA-bound iron by the Fenton reaction), sodium
      azide (a singlet oxygen scavenger), and potassium iodide (an hydroxyl radical
      scavenger) inhibited HP-induced reversion. These results indicate that hydroxyl
      radicals generated from HP by the Fenton reaction, and perhaps singlet oxygen,
      contribute to HP-induced reversion in TA104. However, reduced glutathione
      (reduces Fe3+ to Fe2+ and/or HP to water), diethyldithiocarbamic acid (an
      inhibitor of superoxide dismutase), diethyl maleate (a glutathione scavenger),
      and 3-amino-1,2,4-triazole (an inhibitor of catalase) did not inhibit HP-induced
      reversion in TA104. Thus, superoxide radical anions and HP itself do not appear
      to be the cause of HP-induced reversion in this strain. In experiments on the
      effect of 5 common dietary compounds (beta-carotene, retinoic acid, and vitamins
      A, C and E), chlorophyllin (CHL), and ergothioneine, the frequency of revertants
      in TA104 increased above the spontaneous frequency in the presence of beta
      carotene or vitamin C (about 2-fold) or vitamin A (about 3-fold). The 5 dietary
      antimutagens and CHL did not inhibit HP-induced reversion in TA104. However, L
      ergothioneine inhibited HP-induced reversion in this strain. Therefore, it is
      likely that L-ergothioneine is a scavenger of hydroxyl radicals or an inhibitor
      of their formation, and perhaps of singlet oxygen, at the concentrations tested
      in TA104.

PMID- 1373843
TI  - Induced crossing-over in Drosophila melanogaster germ cells of DNA repair
      proficient and repair-deficient (mei-9L1) males following larval feeding with 5
      azacytidine and mitomycin C.
AB  - The effects of 5-azacytidine (5-AZ) and mitomycin C (MMC), administered by larval
      feeding, on crossing-over were measured in Drosophila melanogaster male germ
      cells of a DNA repair-proficient and a repair-deficient (mei-9L1) strain. Both 5
      AZ and MMC are effective inducers of male crossing-over. The estimated number of
      induced recombination events was higher in repair-proficient than in mei-9L1
      males. The apparently lower sensitivity of mei-9L1 males to crossing-over
      induction may be the result of an incomplete crossing-over process.

PMID- 1373844
TI  - Poly-D-lysine in G2 potentiates chromosome damage induced by X-rays and mitomycin
      C in CHO cells.
AB  - A number of reports suggest that the role of radiation-induced G2 arrest is to
      allow repair of potentially lethal damage in the cells before it comes to
      mitosis. Though the exact nature of the damage undergoing repair during the
      delayed G2 is not known, the yield of chromosomal aberrations observed in
      metaphase seems to be a good parameter to predict reproductive death of cells. In
      a previous paper, we have shown that poly-D-lysine, acting in a fashion
      reminiscent of that of caffeine in mammalian cells, is able to induce a premature
      onset of mitosis concomitant with an increase in the frequency of chromosomal
      aberrations in mutagen-treated plant cells. Cultured CHO cells were pre-exposed
      to either X-rays or mitomycin C and given different doses of the polycationic
      compound during G2 in order to analyze any effect on the frequency of chromatid
      type aberrations as well as any modification of cell-cycle kinetics. A
      potentiation of chromosome damage and a premature arrival at mitosis were
      observed for both mutagens, though the effect was more evident in X-irradiated
      cells.

PMID- 1373846
TI  - X-ray-induced specific-locus mutations in the ad-3 region of two-component
      heterokaryons of Neurospora crassa. X. Heterozygous effects of multilocus
      deletion mutations of genotype ad-3A or ad-3B.
AB  - Previous studies on X-ray-induced irreparable adenine-3 mutations (designated [ad
      3]IR), induced in heterokaryon 12 of Neurospora crassa, demonstrated that they
      were not recessive and exhibited heterozygous effects in terms of markedly
      reduced linear growth rates (de Serres, 1965). Complementation tests with a
      series of tester strains carrying multilocus deletion mutations in the ad-3 and
      immediately adjacent genetic regions demonstrated that X-ray-induced irreparable
      mutations map, in the main part, as a series of overlapping multilocus deletion
      mutations that extend both proximally and distally into the immediately adjacent
      genetic regions, as well as into the 'X' region (a region of unknown, but
      essential function) between ad-3A and ad-3B (de Serres, 1968, 1989). Further
      studies (de Serres and Miller, 1988) have shown that the heterozygous effects of
      multilocus deletion mutations in the ad-3 region can be modified genetically and
      biochemically. In the present paper, the heterozygous effects of X-ray-induced
      multilocus deletion mutations of genotype ad-3A or ad-3B, induced in heterokaryon
      12 (Webber and de Serres, 1965; de Serres, 1988, 1989), have been determined.
      These data show that 57.7% (15/26) of X-ray-induced multilocus deletion mutations
      covering the ad-3A locus have heterozygous effects, in terms of reduced linear
      growth rates, in forced dikaryons with a gene/point mutant at the ad-3B locus and
      80.0% (20/25) in forced dikaryons with a multilocus deletion mutation covering
      the ad-3B locus. In addition, 35.1% (20/57) of X-ray-induced multilocus deletion
      mutations covering the ad-3B locus have heterozygous effects in forced dikaryons
      with a gene/point mutant at the ad-3A locus, and 100.0% (35/35) in forced
      dikaryons with a multilocus deletion mutation covering the ad-3A locus. These
      results demonstrate that the dominant or recessive characteristics of X-ray
      induced specific-locus mutations resulting from multilocus deletion mutations are
      allele specific.

PMID- 1373845
TI  - Prophage induction by DNA topoisomerase II poisons and reactive-oxygen species:
      role of DNA breaks.
AB  - Various compounds were evaluated for their ability to induce prophage lambda in
      the Escherichia coli WP2s(lambda) microscreen assay. The inability of a DNA
      gyrase subunit B inhibitor (novobiocin) to induce prophage indicated that
      inhibition of the gyrase's ATPase was insufficient to elicit the SOS response. In
      contrast, poisons of DNA gyrase subunit A (nalidixic acid and oxolinic acid) were
      the most potent inducers of prophage among the agents examined here. This
      suggested that inhibition of the ligation function of subunit A, which also has a
      DNA nicking activity, likely resulted in DNA breaks that were available (as
      single-stranded DNA) to act as strong SOS-inducing signals, leading to prophage
      induction. Agents that both intercalated and produced reactive-oxygen species
      (the mammalian DNA topoisomerase II poisons, adriamycin, ellipticine, and m-AMSA)
      were the next most potent inducers of prophage. Agents that produced reactive
      oxygen species only (hydrogen peroxide and paraquat) were less potent than
      adriamycin and ellipticine but more potent than m-AMSA. Agents that intercalated
      but did not generate reactive-oxygen species (actinomycin D) or that did neither
      (teniposide) were unable to induce prophage, suggesting that intercalation alone
      may be insufficient to induce prophage. These results illustrate the variety of
      mechanisms (and the relative effectiveness of these mechanisms) by which agents
      can induce prophage. Nonetheless, these agents may induce prophage by producing
      essentially the same type of DNA damage, i.e., DNA strand breaks. The potent
      genotoxicity of the DNA gyrase subunit A poisons illustrates the genotoxic
      consequences of perturbing an important DNA-protein complex such as that formed
      by DNA and DNA topoisomerase.

PMID- 1373847
TI  - Analysis of toxic and mutagenic activities of antiherpesvirus nucleosides against
      HeLa cells and herpes simplex virus type 1.
AB  - The toxic and mutagenic activities of five antiherpesvirus agents to HeLa cells
      and herpes simplex virus type 1 (HSV-1) were investigated. 5-Iodo-2'-deoxyuridine
      (IDU) and 9-beta-D-arabinofuranosyl-adenine (araA) showed very potent inhibitory
      effects on cell growth and the cloning efficiency of HeLa cells, whereas 1-beta-D
      arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), E-5-(2-bromovinyl)-2'
      deoxyuridine (BVDU) and 9-(2-hydroxyethoxymethyl)guanine (ACV) showed less
      inhibitory effect. 50% inhibitory doses of BV-araU and BVDU for cell growth were
      657 and 253 micrograms/ml, respectively. Although the growth inhibitory activity
      of BVDU was very weak, as above, the mutagenic activity of this drug to the
      cells, estimated by induction of colchicine-resistant mutants, was observed to be
      4 micrograms/ml, which was a markedly smaller dose than the inhibitory dose for
      cell growth, and the highest frequency of mutation of the cells was shown at 100
      micrograms/ml of BVDU. This activity was more potent than that of IDU. No
      mutagenic activity of BV-araU, araA and ACV to cells was observed within the
      concentration range of 1-800 micrograms/ml. IDU showed high mutagenic activity to
      HSV-1 growing in human embryo lung fibroblasts, and IDU-resistant mutants were
      induced at a high frequency. BVDU also induced a small amount of BVDU-resistant
      mutant virus, although this drug induced many mutant cells. No mutagenic activity
      of BV-araU, araA and ACV to HSV-1 was observed.

PMID- 1373848
TI  - The effect of the anoxic radiosensitizing agent TAN on induction of revertants by
      gamma-rays and helium ions in Salmonella tester strains.
AB  - The modification effect of the anoxic radiosensitizer TAN on the mutagenesis in
      various Salmonella tester strains after gamma-ray and helium ion irradiation was
      studied. The oxygen enhancement ratios (OER) for all 3 strains on the lethal
      assay after gamma-irradiation are approximately equal to 2. The induction of
      reversions in TA98 and TA100 does not modify under anoxia. The value of OER on
      the mutagenic assay in TA102 equals 1.6. The OER after helium ion irradiation on
      the lethal and mutagenic assays was less than after gamma-irradiation. The
      mutagenesis in 3 strains after irradiation under anoxia is enhanced by TAN. The
      value of the TAN modification effect after gamma-irradiation increases from 2.1
      +/- 0.2 for TA102 to 5.2 +/- 0.4 for TA100. However, the TAN influence on
      mutagenesis in TA100 after helium ion irradiation decreases to 3.1 +/- 0.3. We
      conclude that peculiarities of mutagenesis in various tester strains under anoxia
      with TAN can be explained by considering the nature of premutational DNA damages.

PMID- 1373849
TI  - Spontaneous transposition in the bacteriophage lambda cro gene residing on a
      plasmid.
AB  - A new mutagenesis assay system based on the phage lambda cro repressor gene
      residing on a plasmid was developed. The assay detects mutations in cro that
      decrease the binding of the repressor to the OR operator in an OR PR-lacZ fusion
      present in a lambda prophage. Mutations arose spontaneously during growth of E.
      coli cells harboring cro plasmids at a frequency of 3-6 x 10(-6). Analysis of
      some 200 cro mutants from several 'wild-type' strains revealed a substantial
      fraction of 25-70% insertion events caused by transposition of IS elements. Most
      of the insertions were caused by IS1, but IS5 insertions were observed too. In
      strains harboring Tn10, IS10 was responsible for most insertions. Restriction
      nuclease digestion analysis revealed a preference for insertion of IS10 into the
      C-terminal half of cro, despite the absence of sequences which are known hot
      spots for Tn10 insertions. The frequency of IS1 insertions into cro decreased 25
      60-fold and that of IS10 insertions decreased 200-fold in cells carrying the
      recA56 mutation, suggesting that RecA is involved in transposition of these
      elements. During the logarithmic phase of growth, the mutation frequency was
      constant for at least 22 generations; however, upon continuous incubation at the
      stationary phase, the mutation frequency gradually increased, yielding a 3-fold
      increase in the frequency of insertion and a 4-5-fold increase in point mutation.
      Genomic Southern analysis of chromosomal IS elements in cells which underwent a
      transposition from the chromosome into the cro plasmid revealed that the number
      and distribution of IS1 and IS5 were usually unaltered compared to cells which
      did not undergo a transposition event. In contrast, essentially each IS10
      transposition was accompanied by multiple events which led to changes in the
      number and distribution of chromosomal IS10 elements.

PMID- 1373850
TI  - All colonies of CHO-K1 cells surviving gamma-irradiation contain non-viable
      cells.
AB  - This paper addresses the problem of the production of defective cells within
      clones arising from irradiated progenitor cells and is specifically aimed at
      answering the question of whether lethal mutations result from a generalised
      effect which lowers the ability of all the progeny to divide successfully or
      whether it represents a late expressed but unique lethal defect induced by
      radiation which occurs in some cells only and which causes those cells only to
      cease dividing. The results obtained from autoradiographic analysis of cells
      within individual surviving colonies (i.e. containing more than 150 cells)
      suggests that some cells in all clones are not synthesizing DNA over a 9-h period
      and that the proportion of non-synthesising cells rises with increasing dose of
      radiation from less than 3% in the controls to 80-85% after a progenitor dose of
      12.5 Gy. Because of the possibility that cells had longer division times post
      irradiation, these results were repeated using Ki67 antibody labelling, a
      technique which identifies cells which are in cycle. The results were similar.
      This suggests the non-labelled cells were not reproducing. Both techniques were
      also used to look at the % labelling of morphologically abnormal cells in the
      colonies. The results suggested that up to 35% of these abnormal cells were
      actively cycling and about 20% were synthesising DNA. Abnormal cells did not
      appear in subcultures of survivor progeny suggesting that they may have failed to
      replate successfully and may contribute to the lethally mutated population. The
      idea that radiation induces a general instability in the cell population was
      supported by experiments where growth and the plating efficiency of irradiated
      progeny was measured daily. This revealed that the growth curves deviated from
      the control by a constant factor suggesting a division probability of about 70%
      of the control level after a progenitor dose of 10 Gy. The results are discussed
      in the context of their significance for survival curve analysis and for
      radiotherapy and radiation protection results.

PMID- 1373851
TI  - Radiation and transposon-induced genetic damage in Drosophila melanogaster: X-ray
      dose-response and synergism with DNA-repair deficiency.
AB  - The interaction of X-ray-induced and transposon-induced damage was investigated
      in P-M hybrid dysgenesis in Drosophila melanogaster. The X-ray dose-response of
      330-1320 rad was monitored for sterility, fecundity and partial X/Y chromosome
      loss among F2 progeny derived from the dysgenic cross of M strain females xP
      strain males (cross A) and its reciprocal (cross B), using a weaker and the
      standard Harwich P strain subline. The synergistic effect of P element activity
      and X-rays on sterility was observed only in cross A hybrids and the dose
      response was nonlinear in hybrids derived from the strong standard reference
      Harwich subline, Hw. This finding suggests that the lesions induced by both
      mutator systems which produce the synergistic effect are two-break events. The
      effect of increasing dose on the decline of fecundity was synergistic, but
      linear, in hybrids of either subline. There was no interaction evident and thus
      no synergism in X/Y nondisjunction and in partial Y chromosome loss measured by
      the loss of the Bs marker alone or together with the y+ marker. Interaction was
      detected in the loss of the y+ marker alone from the X and Y chromosomes. The
      possible three-way interaction of X-rays (660 rad), post-replication repair
      deficiency and P element mobility was assessed by measuring transmission
      distortion in dysgenic males derived from the II2 P strain. X-Irradiation of
      spermatids significantly increased the preferential elimination of the P-element
      bearing second chromosome in mei-41, DNA-repair-deficient dysgenic males, but had
      no effect in their DNA-repair-proficient brothers. These findings indicate that
      the post-replication repair pathway is required for processing lesions induced by
      the combined effect of P element mobility and X-rays, and that the unrepaired
      lesions ultimately lead to chromosome loss.

PMID- 1373852
TI  - Local sequence dependence of rate of base replacement in mammals.
AB  - I have analysed the local sequence context of base replacement changes in 78
      processed pseudogenes. Transversions occur more often than transitions in a ratio
      of 3.37 to 1, and G:C is replaced 1.4 times more frequently than A:T. In
      addition, the bases to the 5' and 3' of the mutating base also influence the rate
      at which bases change, purine:pyrimidine and pyrimidine:purine pairs changing 1.2
      times as fast as purine:purine and pyrimidine:pyrimidine pairs. I discuss
      implications of this for the mechanism of DNA polymerization in mammals.

PMID- 1373853
TI  - Analysis of the spectrum of mutations induced by the rad3-102 mutator allele of
      yeast.
AB  - The product of the RAD3 gene of Saccharomyces cerevisiae is required for mitotic
      cell viability and excision repair of UV-induced pyrimidine dimers. Certain rad3
      mutant alleles (originally called rem1) increase the rates of both spontaneous
      mitotic recombination and mutation. The increase in mutation rates is not
      dependent upon the presence of the RAD6 error-prone pathway. The mutator
      phenotype suggests that the wild-type RAD3 gene product may be involved in the
      maintenance of fidelity of DNA replication in addition to its known role in
      excision repair. To investigate the role that RAD3 might play in mutation
      avoidance, we have utilized a well-characterized shuttle vector system to study
      the mutational spectrum occurring in rad3-102 strains and compare it to that seen
      in RAD3 strains. The results put constraints on the role that the rad-102 mutant
      gene product must play if the RAD3 protein is a component of the replication
      complex. Alternatively, the mutational spectrum is consistent with the hypothesis
      that the rad3-102 mutant protein interferes with postreplication mismatch repair.

PMID- 1373854
TI  - Properties of R-plasmid pEB017, which confers both enhanced UV-radiation
      resistance and mutability to wild-type, recA and umuC strains of Escherichia coli
      K12.
AB  - The R-plasmid, pEB017, restored recombination ability to recA56 and conferred
      enhanced resistance to UV-radiation and enhanced UV-radiation mutability to wild
      type, recA56 and umuC36 strains of Escherichia coli K12. Comparatively, pEB017
      enhanced UV-radiation mutability in a umuC strain, and also enhanced UV-radiation
      and nitrofuran mutability in a wild-type strain several-fold more than did
      another R-plasmid, pKM101. Plasmid pEB017 also mediated about a 3-fold
      enhancement of the SOS induction of beta-galactosidase synthesis in a recA
      strain, compared with the normal recA+ gene of E. coli. A BamHI fragment of
      pEB017 DNA was cloned into plasmid vector pBR322 to yield pEB021. The BamHI
      fragment in pEB021 (3.5 kb) is about 170 bp longer between the BamHI and PstI
      sites on the left end of the recA-like fragment, compared with published data on
      a similarly cloned recA gene from E. coli. Plasmid pEB021 conferred enhanced
      resistance to UV-radiation and enhanced UV-radiation mutability in wild-type and
      recA strains, and restored recombination ability in a recA strain. The
      introduction of pEB021 into a umuC strain made the cells slightly more resistant
      to killing by UV-irradiation, and promoted a small amount of UV-mutability in an
      otherwise nonmutable strain. These results suggest that R-plasmid pEB017 has a
      recA-like gene that mediates the enhanced resistance to UV-radiation and enhanced
      UV-radiation mutability, but which seems different in several important aspects
      from the normal recA gene in E. coli.

PMID- 1373855
TI  - Multivariate statistical analysis of mutational spectra of alkylating agents.
AB  - A series of multivariate statistical methods were used to explore the current
      knowledge on the mutational spectra of alkylating agents (AA) in bacterial and
      mammalian cells. The data relative to lac I and gpt genes of Escherichia coli
      were considered. The analysis focused on the distribution of GC to AT
      transitions, which account for the majority of AA-induced mutations. The
      statistical analysis of 15 different mutational spectra obtained by various
      laboratories pointed to a number of biological factors involved in the mutational
      process. First of all, factor and cluster analyses demonstrated that the
      mutational profiles obtained in mammalian cells form a homogeneous cluster
      different from the cluster formed by the bacterial cell mutational spectra. SN1
      type AAs give rise to classes of mutational spectra statistically different from
      the spectra induced by the SN2-type AAs. The analysis of the mutated sequences of
      both genes pointed to a correlation between mutation induction by SN1 AAs, which
      react through a positively charged alkylating intermediate, and the occurrence of
      mutations at guanines preceded 5' by a purine. Moreover, our statistical analysis
      showed that the distribution of AA-induced mutations is not affected by the
      transcriptional activity of the target gene, but is strongly determined by the
      sequence specificity of AA-induced mutagenesis and by the structure of the target
      proteins. The agreement of our results with the findings of previous studies
      indicates that the multivariate data analysis methods are a sensitive and
      reliable tool for exploring the mechanisms underlying complex biological
      processes. The novelty of the present results lies in their quantitative
      character, and in the clarity of the graphical displays. We propose the use of
      this methodological approach to explore the large bulk of information available
      on mutational spectra.

PMID- 1373856
TI  - A comparison of induced mutation at homologous alleles of the tk locus in human
      cells. II. Molecular analysis of mutants.
AB  - Previously we described the dose-response relationship for X-ray-induced mutation
      of the two homologous alleles of the thymidine kinase (tk) gene in a human
      lymphoblastoid cell line (Amundson and Liber, 1991). The two alleles were
      differentially mutable by X-rays, with one allele 6-10 times more mutable than
      the other. This difference was shown to be due to the virtual absence of the
      class of slow growth mutants from one allele. In the present report, restriction
      fragment length polymorphism (RFLP) analyses of informative markers along
      chromosome 17 have been used to delineate a region of chromosome 17 in which
      heterozygosity is lost with relatively high frequency among slow growth TK-
      mutants from the more mutable allele. However, loss of heterozygosity of this
      region has never been observed in normal growth mutants obtained from the more
      mutable allele, or in TK- mutants from the other, less mutable, allele. This may
      indicate the presence of a heterozygous essential gene on chromosome 17 distal to
      TK1.

PMID- 1373857
TI  - Analysis of chromosome aberrations induced by U5 RNA.
AB  - A small nuclear RNA, U5, was reported previously to induce chromosome
      aberrations. This was further analyzed in the present study. An in vitro
      transcript from a synthetic DNA template, which corresponds to the 3' half of the
      first stem of U5, induced chromosome aberrations upon transfection of a rat
      fibroblast, 3Y1 cells. Introduction of an expression vector construct carrying
      the same part of the U5 sequence resulted in morphological transformation of the
      cells. A cytological analysis of the transformed cells showed chromosome
      abnormalities similar to those induced by the RNAs. It was also shown that the
      frequency of chromosome aberrations in the transformed cells increased by
      elevating the level of the transcript. A possible mechanism of chromosome
      aberrations by the RNAs is discussed.

PMID- 1373858
TI  - Mutagenic activity of nine N,N-disubstituted hydrazines in the
      Salmonella/mammalian microsome assay.
AB  - The mutagenic activity of N,N-dimethyl-, N,N-diethyl-, N,N-dibutyl-, N,N
      diisobutyl-, N,N-di(p-tolyl)-, N-ethyl-N-phenyl-, N,N-dibenzyl-, N,N-diphenyl-
      and N,N-diisopropylhydrazine was examined in the Salmonella/mammalian microsome
      assay using the strains TA1535, TA1537, TA97, TA98, TA100, TA102 and TA1530. All
      nine hydrazines were mutagenic in at least one tester strain, although of
      borderline significance for some of the compounds. The mutagenic potencies of the
      hydrazines varied 2-3 orders of magnitude, from very weak to moderate mutagenic
      activity. In general, the addition of S9 resulted in a lowering of the mutagenic
      activity and a lowering of the toxic properties of the hydrazines. The test
      results were relatively difficult to evaluate due to toxic effects of many of the
      test compounds on the test bacteria which may have resulted in an underestimation
      of the mutagenic potencies of some of the compounds. The pattern of mutagenic
      activity of the hydrazines in the different tester strains indicates that more
      than one mechanism of action may be involved in the mutagenicity.

PMID- 1373859
TI  - Comparison of the mutagenicity of quinoline and all monohydroxyquinolines with a
      series of arene oxide, trans-dihydrodiol, diol epoxide, N-oxide and arene hydrate
      derivatives of quinoline in the Ames/Salmonella microsome test.
AB  - Fourteen new quinoline derivatives were synthesised and their mutagenicity
      compared in the Ames test using Salmonella typhimurium TA100 as indicator strain
      with and without (Aroclor-induced) S9 mix. None of the synthesised quinoline
      derivatives had to our knowledge been examined before in the Ames test. Quinoline
      and the monohydroxyquinolines were included as reference compounds. Three of the
      new derivatives, i.e., quinoline 7,8-oxide, N-methyl-quinoline 5,6-oxide and
      trans-quinoline-5,6,7,8-dioxide appeared to be mutagenic. Quinoline 7,8-oxide was
      positive only in the presence of S9 mix, the specific mutagenicity amounting to
      2498 +/- 96 and 1289 +/- 120 revertants per mumole with 20 and 10% S9 in the mix,
      respectively. Both N-methyl-quinoline 5,6-oxide and trans-quinoline-5,6,7,8
      dioxide were weakly positive, the former only in the presence of the S9 mix, and
      the latter irrespective of the presence of S9 mix, the specific mutagenicity
      amounting to 134 +/- 6 and 123 +/- 10 revertants per mumole, respectively. The
      mutagenic potency of quinoline 7,8-oxide was of the same order as that of
      quinoline itself and was distinctly lower than that of 8-hydroxyquinoline.
      Inconclusive results were obtained with trans-7,8-dihydroxy-7,8-dihydroquinoline,
      5,6-dihydroxy-7,8-epoxy-5,6,7,8-tetrahydroquinoline and 8-hydroxyquinoline-N
      oxide; if these compounds are mutagenic their mutagenic potency would be at least
      20-30 times lower than that of the parent compounds. None of the other chemically
      synthesised quinoline derivatives showed mutagenic activity with TA100 either in
      the presence or in the absence of S9 mix. The results obtained with the reference
      compounds were in accordance with literature data.

PMID- 1373860
TI  - Biologic markers in hospital workers exposed to low levels of ethylene oxide.
AB  - Operators of hospital sterilizers that use ethylene oxide were studied to
      determine if there was a relationship between exposure and a battery of
      biological markers. A total of 73 workers from nine hospitals in the United
      States (U.S.) and one hospital in Mexico City was evaluated for ethylene oxide
      exposure during four months prior to collection of peripheral blood. The
      frequency of hemoglobin adducts (p = 0.0006) and sister-chromatid exchanges
      (SCEs) (p = 0.002) increased with cumulative exposure to ethylene oxide in U.S.
      subjects when controlling by regression analysis for various confounding factors,
      including cigarette smoking. Hemoglobin adducts, but not SCEs, were also
      increased in Mexican subjects (p = 0.0012). Chromosomal micronuclei showed no
      consistent relationship with exposure. The U.S. study participants were
      classified by four-month cumulative exposure levels of 10 ppm-h (n = 8), greater
      than 0 to 32 ppm-h (n = 32) and greater than 32 ppm-h (n = 11) of ethylene oxide
      exposure. The group with an exposure of greater than 32 ppm-h had an increased
      frequency of hemoglobin adducts (p = 0.002) and SCEs (p = 0.0001) compared to the
      nonexposed group. The estimated mean of the 8-h time-weighted average (8-h TWA)
      exposure levels for the highest U.S. exposure group (greater than 32 ppm-h) was
      0.16 +/- 0.007 ppm (mean +/- SD). A similar exposure-related differential was
      observed in the Mexican subjects for hemoglobin adducts (p = 0.04) but not for
      SCEs. The latter finding may have been due to longer shipping times for the
      specimens in the cytogenetic assays. The estimated mean of the 8-h TWA exposure
      levels for the highest Mexican exposure group (greater than 32 ppm-h) was 0.48 +/
      0.08 ppm. This study is the third to suggest that exposures less than the U.S.
      OSHA standard of 1 ppm 8-h TWA result in biochemical and biologic changes. It is
      not known whether these changes may be indicative of increased risk of disease;
      however, they do appear to reflect exposure to relatively low levels of ethylene
      oxide. The exact meaning of these changes is unknown.

PMID- 1373861
TI  - Sister-chromatid exchange and chromosome aberrations induced by paracetamol in
      vivo in bone-marrow cells of mice.
AB  - Sister-chromatid exchange (SCE) and chromosome aberrations (CA) induced by
      paracetamol (PC), a common analgesic, were studied in vivo on bone-marrow cells
      of mice. The trend tests for the evidence of dose-response effects for both SCE
      and CA were significant. The significant increase in SCE as well as CA induced by
      PC may be attributed to the fact that PC can induce genotoxicity through DNA
      damage. Thus, the present study indicates that PC was genotoxic in vivo in bone
      marrow cells of mice.

PMID- 1373862
TI  - The in vivo micronucleus test in human capillary blood lymphocytes:
      methodological studies and effect of ageing.
AB  - The in vivo micronucleus test in lymphocytes of human capillary blood collected
      by skin puncture is described. This method needs only 1-2 drops of finger blood.
      The normal value of micronucleus frequencies in lymphocytes from 250 healthy
      persons aged 6-88 years was determined. The upper limits of normal values were
      estimated by means of percentile. The 95th percentiles were 1/1000 and 1.5/1000
      for the 6-45-year age group and the 46-88-year age group, respectively. There was
      no significant difference in micronucleus frequency between men and women. On the
      basis of micronucleus assays in more than 3000 cases, we consider that the
      micronucleus test in human capillary blood lymphocytes is a rapid, convenient and
      sensitive procedure for monitoring a human population exposed to environmental
      and occupational mutagens and carcinogens.

PMID- 1373863
TI  - Collaborative study of mutagenicity with Salmonella typhimurium TA102.
AB  - Thirty compounds of various chemical classes were investigated for mutagenicity
      in a collaborative study (3 laboratories) using Salmonella typhimurium TA102.
      With 5 compounds, namely hydrazine sulfate, phenylhydrazine, hydralazine,
      glutardialdehyde and glyoxal, mutagenicity was detected by all laboratories.
      Formaldehyde was assessed as weakly mutagenic in only 1 of 3 laboratories. The
      remaining 24 agents were uniformly described as non-genotoxic in TA102. In spite
      of the overall good qualitative agreement in the mutagenicity results between the
      3 laboratories some quantitative discrepancies occurred in the dose response of
      the mutagenic compounds. Varying inter- and intra-laboratory differences in the
      spontaneous rate of revertants were obtained. The usefulness of the tester strain
      TA102 in routine mutagenicity testing is discussed.

PMID- 1373864
TI  - Study of unscheduled DNA synthesis following exposure of human cells to arecoline
      and extracts of betel nut in vitro.
AB  - Aqueous, acetic acid, hydrochloric acid and ethanol extracts of betel nut (Areca
      catechu L.) have been found to induce unscheduled DNA synthesis in Hep 2 cells
      obtained from human larynx carcinoma, in vitro. Different concentrations of
      extracts of betel nut induced dose-dependent unscheduled DNA synthesis in Hep 2
      cells. Together with the viability of the Hep 2 cells, our results indicate that
      the aqueous and acetic acid extracts of betel nut induce relatively more
      unscheduled DNA synthesis than the hydrochloric acid and ethanol extracts and
      arecoline. The carcinogenic potency of raw and unprocessed betel nut of North
      East India used in this study is discussed.

PMID- 1373865
TI  - Enhancement of the mutagenicity of IQ and MeIQ by nitrite in the Salmonella
      system.
AB  - The fried food mutagens IQ, MeIQ, Glu-P-1 and Trp-P-2 were treated with nitrite
      at pH 3.0 for 1 h at 37 degrees C. The resulting reaction mixtures were tested
      for mutagenicity towards Salmonella typhimurium TA97, TA98, TA100 and TA1535. Glu
      P-1 and Trp-P-2 were readily converted to weak or non-mutagenic deaminated
      compounds, whereas IQ and MeIQ were converted to extremely strong mutagenic
      derivatives in both the presence and the absence of rat liver S9 mix. The
      mutagenicity of MeIQ in TA98 was enhanced by nitrite up to 3-fold, while that of
      nitrosated MeIQ was further enhanced by S9 mix up to 15-fold. The nitrosation
      products of MeIQ were resolved into 7 bands by TLC on silica gel plate. Bands I,
      III, V and VI were highly mutagenic to both TA98 and TA100. The experimental
      results suggest that the non-enzymatic formation of direct-acting mutagens from
      indirect-acting mutagens such as IQ or MeIQ might be physiologically important,
      especially with regard to the etiology of human gastrointestinal tract tumors.

PMID- 1373866
TI  - Structure-activity relationships of epoxides: induction of sister-chromatid
      exchanges in V79 cells by enantiomeric epoxides.
AB  - Analysis of SCE frequencies in Chinese hamster V79 cells was used to investigate
      the influence of the stereoisomeric forms of epoxides in mammalian genotoxicity
      tests. The SCE-inducing potency of 12 pairs of (R)- and (S)-enantiomeric epoxides
      which differed in the degree of substitution of the oxirane ring was determined.
      Of these, 2 pairs of epoxides failed to induce SCE. Different SCE-inducing
      potencies between the (R)- and (S)-enantiomers were shown for 5 epoxides. This
      study demonstrates that stereoselectivity might play an important role in
      genotoxicity testing of chemicals with asymmetric C atoms.

PMID- 1373867
TI  - Hepatitis B and hepatitis C in emergency department patients.
AB  - BACKGROUND: Infections with hepatitis B virus (HBV), hepatitis C virus (HCV), and
      the human immunodeficiency virus type 1 (HIV-1) are common in inner-city
      populations, but their frequency and interrelations are not well established.
      METHODS: During a six-week period, excess serum samples were collected, along
      with information on risk factors, from all adult patients presenting to an inner
      city emergency department. The samples were assayed for hepatitis B surface
      antigen (HBsAg) and antibodies to HCV and HIV-1. RESULTS: Of the 2523 patients
      tested, 612 (24 percent) were infected with at least one of the three viruses.
      Five percent were seropositive for HBV, 18 percent for HCV, and 6 percent for HIV
      1. HCV was found in 145 of the 175 intravenous drug users (83 percent), 36 of the
      171 transfusion recipients (21 percent), and 5 of the 24 homosexual men (21
      percent). Among black men 35 to 44 years of age, the seroprevalence of HCV was 51
      percent. HBsAg was present in 9 percent of those whose only identifiable risk was
      possible heterosexual exposure. At least one viral marker was found in about 30
      percent of the patients who were actively bleeding or in whom procedures were
      performed. Testing for HIV-1 alone would have failed to identify 87 percent of
      the patients infected with HBV and 80 percent of those infected with HCV.
      CONCLUSIONS: In a population of patients in an inner-city emergency room, HBV,
      HCV, and HIV-1 are all highly prevalent. However, routine screening for HIV-1
      alone would identify only a small fraction of the patients who pose risks of
      severe viral infections, including HBV and HCV, to providers.

PMID- 1373868
TI  - A eukaryotic DNA glycosylase/lyase recognizing ultraviolet light-induced
      pyrimidine dimers.
AB  - Cyclobutane pyrimidine dimers (CPDs) are the predominant product of photodamage
      in DNA after exposure of cells to ultraviolet light and are cytotoxic, mutagenic
      and carcinogenic in a variety of cellular and animal systems. In prokaryotes,
      enzymes and protein complexes have been characterized that remove or reverse CPDs
      in DNA. Micrococcus luteus and T4 phage-infected Escherichia coli contain a
      specific N-glycosylase/apurinic-apyrimidinic lyase that catalyses a two-step DNA
      incision process at sites of CPDs, thus initiating base excision repair of these
      lesions. It is well established that CPDs are recognized and removed from
      eukaryotic DNA by excision repair processes but very little information exists
      concerning the nature of the proteins involved in CPD recognition and DNA
      incision events. We report here that an enzyme functionally similar to the
      prokaryotic N-glycosylase/apurinic-apyrimidinic lyases exists in Saccharomyces
      cerevisiae. To our knowledge, this is the first time such an activity has been
      found in a eukaryote and is also the first example of an organism having both
      direct reversal and base excision repair pathways for the removal of CPDs from
      DNA.

PMID- 1373869
TI  - BAY K 8644 stimulates glucose-dependent rise of cytoplasmic Ca2+ in
      hyperpolarized pancreatic beta-cells.
AB  - The effect of BAY K 8644 on the cytoplasmic Ca2+ concentration ([Ca2+]i) was
      studied in pancreatic beta-cells hyperpolarized by the K+ channel-activating
      agent diazoxide. After 50-60 min preexposure to 0-20 mM glucose in the presence
      of 400 microM diazoxide [Ca2+]i was close to the level in unstimulated beta
      cells. The addition of 5 microM BAY K 8644 then triggered a rise of [Ca2+]i
      dependent on Ca2+ influx. The magnitude of the BAY K 8644 effect increased with
      the glucose concentration and was almost 10-fold higher in 20 mM than in the
      absence of the sugar. It is concluded that glucose can modulate Ca2+ entry
      through the voltage-dependent channels by a mechanism additional to
      depolarization. This action may help to explain why previous exposure to the
      sugar results in an augmented insulin response to a second challenge.

PMID- 1373870
TI  - Hepatitis C virus infection in kidney graft recipients.

PMID- 1373871
TI  - Managing a surgical patient who has diabetes.

PMID- 1373872
TI  - Mutations of the p53 gene in human myeloma cell lines.
AB  - Mutations affecting the p53 gene have been found associated with many human
      malignancies, but little is as yet known about multiple myeloma. We investigated
      p53 gene alterations in 10 human myeloma cell lines (HMCL), half of these being
      dependent upon exogenous interleukin 6 (IL-6) for in vitro growth, similar to
      freshly explanted myeloma cells. Using a polymerase chain reaction-single-strand
      conformation polymorphism (PCR-SSCP) approach, eight of the 10 HMCL were found to
      bear a mutated p53 gene. All the mutations were single base substitutions with a
      predominance of G:C to A:T transitions. There was no apparent relation between
      the presence of a mutation and IL-6 requirement of the cell line. Interestingly,
      in two cell lines (XG-2 and XG-4) the SSCP pattern showed the presence of both
      the wild-type and the mutated allele and, upon reverse PCR on RNA, both alleles
      were found to be concomitantly expressed at the RNA level. Moreover, three
      freshly explanted tumor samples had the same p53 gene status (mutated versus wild
      type) as the HMCL that were derived from them. These results show that p53
      mutations are frequent in HMCL. Although no apparent relation could be evidenced
      with the loss of exogenous IL-6 requirement, it may prove interesting to
      investigate further potential relations between the presence of a mutated p53
      allele and gradual autonomy for cell growth.

PMID- 1373873
TI  - Human protein-tyrosine kinase gene HCK: expression and structural analysis of the
      promoter region.
AB  - The vertebrate gene HCK encodes a protein-tyrosine kinase that is closely related
      to the product of the proto-oncogene SRC. HCK is expressed principally in
      monocytic and granulocytic hematopoietic cells, in coordination with
      differentiation of these cells. Here we report an initial description of the
      mechanisms by which expression of human HCK is controlled. Induction of the gene
      during differentiation was manifested by an increase in the steady-state levels
      of HCK RNA and protein product. The accumulation of RNA apparently resulted from
      modulation of transcription itself, since no change occurred in the stability of
      the transcripts. Transcription initiated at multiple sites, clustered c. 145
      nucleotides upstream of the first intron of HCK. The sequence of 660 bp upstream
      of the major initiation site was determined, revealing candidate binding sites
      for Sp1 and AP-2 transcription factors, but neither TATA nor CAAT elements.
      Comparison to the same region of the mouse hck locus showed five small regions of
      similarity, only two of which were topographically analogous between the two
      sequences. It appears that expression of HCK is regulated primarily through
      control of transcription, but the mechanisms by which tissue-specific expression
      and increase of transcription during differentiation are achieved remain to be
      explored.

PMID- 1373874
TI  - Bcl-2 confers growth and survival advantage to interleukin 7-dependent early pre
      B cells which become factor independent by a multistep process in culture.
AB  - Early pre-B cells derived from mouse lymphoid bone marrow cultures were expanded
      on a surrogate stromal cell line composed of NIH3T3 fibroblasts engineered to
      secrete interleukin 7 (IL-7). Three immortal, IL-7-dependent cell lines were
      generated and infected with recombinant retroviruses to determine the effects of
      the human follicular B-cell lymphoma gene, bcl-2, on immature stages of B-cell
      development. Cells expressing bcl-2 grew at rates similar to those of control
      (vector only) cells when plated on bone marrow stromal lines, but exhibited a c.
      two-fold net proliferative advantage when grown in liquid medium supplemented
      with IL-7 alone. Bcl-2 prevented apoptosis when the infected early pre-B-cell
      lines were deprived of IL-7 and other growth factors provided by stromal cells.
      Following factor deprivation, a subset of cells expressing bcl-2 survived
      indefinitely. Two such cultures spontaneously gave rise to factor-independent
      variants which grew slowly in unsupplemented liquid culture and formed agar
      colonies, yet still responded positively to IL-7 and kit ligand, and negatively
      to gamma-interferon. Bcl-2 thus provides a survival capacity and modest growth
      advantage to early pre-B cells, which may recapitulate its effects in human B
      cells bearing t(14;18) translocations and ultimately contribute to
      transformation.

PMID- 1373875
TI  - Characterization of the 5' untranslated region of the human c-fgr gene and
      identification of the major myelomonocytic c-fgr promoter.
AB  - In this study, we have characterized the 5' region of the human c-fgr proto
      oncogene and identified the major myelomonocytic c-fgr promoter. Seven distinct
      5' untranslated exons were identified and localized to a region extending 13 kb
      upstream from the first coding exon. Two major promoters were identified, one
      utilized exclusively in Epstein-Barr virus (EBV)-infected B-lymphocyte cell
      lines, and the other functional only in myelomonocytic cells. Differential
      promoter utilization and alternative splicing of the 5' untranslated exons give
      rise to at least six distinct c-fgr mRNA species that differ only in their 5'
      untranslated regions. Two major mRNAs were identified, c-fgr A and c-fgr 4; these
      two mRNAs were detected exclusively in EBV-infected B-lymphocyte cell lines and
      myelomonocytic cells respectively. We have previously demonstrated that c-fgr is
      transcriptionally activated in U937 cells treated with either 12-O-tetradecanoyl
      phorbol-13-acetate (TPA) or cycloheximide (CHX). We now show that a DNA fragment
      extending from -772 to +97 (with respect to the transcription initiation site
      upstream from exon M4) is responsive to TPA but not CHX treatment in U937 cells.
      These results suggest that TPA and CHX induce c-fgr mRNA accumulation by
      different mechanisms.

PMID- 1373877
TI  - Characterization of a class 3 tyrosine kinase.
AB  - In an effort to identify unique tyrosine kinases found in human leukemia cell
      lines, we utilized polymerase chain reaction (PCR) technology and degenerate
      oligonucleotide primers to produce a cDNA library of kinase catalytic domains
      found in the human monocytic cell line AML-193. This search yielded a member of
      the class 3 tyrosine kinases closely related to the murine kinase FD-22. Previous
      work has identified this kinase as JAK1. This class of tyrosine kinases is
      characterized by being ubiquitously expressed, lacking both a ligand-binding
      domain and a SH2 domain, while containing a second domain similar to a degenerate
      kinase domain. Our studies focused on the further characterization of this class
      3 tyrosine kinase using Northern blot analysis to demonstrate an increase in
      steady-state mRNA by interferon-gamma in human monocytes. A human-hamster somatic
      cell hybrid panel and linkage mapping was used to assign JAK1 (aml-116) to human
      chromosome 1.

PMID- 1373878
TI  - Phosphorylation of the retinoblastoma protein is modulated in mouse kidney cells
      infected with polyomavirus.
AB  - Lytic infection with polyomavirus, an oncogenic DNA-containing virus, leads in G0
      arrested primary baby mouse kidney (BMK) cell cultures to a mitotic host
      reaction. In the present work, we examined the expression of the retinoblastoma
      gene (RB) and of its product (Rb) in virus-infected BMK with the aim of
      correlating its modulation with the sequential activation of cellular processes
      leading to the induction of S phase by virus. In contrast to cell cycle-regulated
      genes whose expression is induced by viral infection, expression of RB is not
      altered during the transition from G0/G1 to S phase. In BMK cell cultures
      irreversibly arrested in the G0 phase of the cell cycle, an unphosphorylated
      species is the only detectable form of the RB protein (Rb). Time course analysis
      showed that in polyoma-infected cells induced to re-enter the S phase of the cell
      cycle the appearance of the phosphorylated forms of Rb coincided in time with the
      accumulation of large T antigen and preceded DNA synthesis. During the late phase
      of infection, the majority of Rb was present as phosphorylated forms. Ongoing DNA
      synthesis was not required for the cells to phosphorylate Rb, indicating that
      this post-translational modification takes place during the activation of the
      cellular DNA-synthesizing apparatus. Using hamster anti-polyoma tumor serum, it
      was observed that the underphosphorylated form of Rb co-precipitated with polyoma
      large T antigen extracted from infected cells late during infection. Our data add
      more evidence to the proposal that interactions between viral early proteins
      encoded by DNA tumor viruses and the product of RB may play a pivotal role in the
      mitogenic effect induced by viral infection.

PMID- 1373876
TI  - Oncogene-mediated transformation of fetal rat colon in vitro.
AB  - Short-term maintenance of fetal rat colonic tissue in vitro has been demonstrated
      using a collagen matrix organ culture system. The introduction of single (v-myc,
      v-rasH, v-src) oncogenes or combinations of oncogenes (v-myc/rasH, v-myc/src)
      into normal colon mucosal elements was established using retroviral vectors,
      resulting in enhanced proliferation and migration of epithelial cells from the
      lumen of tissue implants. Expression of a single oncogene in normal colon
      epithelium did not result in the establishment of cell lines. In contrast,
      expression of cooperating oncogenic elements resulted in cell lines in greater
      than 80% of experiments, revealing different morphological characteristics
      dependent upon the oncogene combination used. Confirmation of the expression of
      viral transcripts was determined using Northern blot analysis and viral
      oncoprotein expression using Western blot analysis (p21) and an
      immunoprecipitation kinase assay (src). Expression of keratin filaments was lost
      following passaging of cell lines but could be induced by the myc/ras
      transformants by growth on Rat-1 feeder layers. This induction phenomenon was not
      observed with myc/src lines, and although these expressed high levels of sucrase
      isomaltase the epithelial origin of these cells is unclear. Karyotypic analysis
      performed on three myc/ras-transformed cell lines revealed a normal chromosome
      complement associated with transformation. In this report we describe a novel in
      vitro transformation system for normal rat colonic epithelium mediated by the
      introduction of oncogene elements using different retroviral vector constructs.
      The potential to generate cell lines representing different stages of neoplastic
      progression using relevant genetic components presents significant advantages for
      the study of cellular and molecular interactions underlying colon neoplastic
      progression.

PMID- 1373879
TI  - Expression of truncated transcripts of the proto-oncogene c-fps/fes in human
      lymphoma and lymphoid leukemia cell lines.
AB  - The human c-fps/fes proto-oncogene is expressed as a transcript of about 3.0 kb
      in both normal and leukemic myeloid cells. We have detected truncated c-fps/fes
      transcripts of about 0.9 kb in a panel of human lymphoma and lymphoid leukemia
      cell lines, but not in normal untransformed hematopoietic cells. Analysis of the
      chromatin structure of the c-fps/fes gene revealed DNAase I-hypersensitive sites
      in the 5' region of the gene and in exon 16. The presence and absence of these
      sites correlates with the expression of the 3.0 kb and 0.9 kb c-fps/fes RNAs
      respectively. The truncated transcripts initiate at two distinct sites within
      exon 16 of the c-fps/fes gene. The genomic region 5' to the transcription
      initiation sites is G+C rich but does not contain typical promoter consensus
      sequences. Sequence analysis of a cDNA clone of the truncated c-fps/fes
      transcripts did not reveal any point mutation and the truncated transcripts are
      normally spliced using the regular splice donor and acceptor sites. A putative
      open reading frame encompasses the phosphotransfer motif and the
      autophosphorylation site of the fps/fes kinase domain. In vitro
      transcription/translation of a cDNA clone corresponding to the truncated c
      fps/fes transcripts revealed a protein of 17 kDa. There are no translocations or
      rearrangements in or around the c-fps/fes gene in cell lines which express the
      truncated c-fps/fes transcripts. This alternative transcription of c-fps/fes may
      indicate a novel activation process of this proto-oncogene.

PMID- 1373880
TI  - Molecular cloning and characterization of the t(2;14) translocation associated
      with childhood chronic lymphocytic leukemia.
AB  - Two rare cases of chronic lymphocytic leukemia (CLL) in children, patients AS and
      LH, have been found to be associated with a unique chromosomal translocation,
      t(2;14)(p13;q32). Previous studies have shown the breakpoints of this
      translocation to be in the gamma 2 switch region of the Ig heavy-chain locus on
      chromosome 14 and in an uncharacterized region of chromosome 2. We have cloned
      and characterized the translocation breakpoints to examine the possibility that
      an oncogene contributed to the pathogenesis of these cases of CLL. Sequence
      analysis of AS and LH breakpoints established that the chromosome 2 breakage in
      the two patients occurred only 38 bp apart and within a strong non-methylated CpG
      island. Furthermore, human probes from the region cross-hybridized to other
      species, indicating strong evolutionary conservation. Northern analysis using the
      chromosome 2 probes detected a 2.85-kb transcript in the tumor cells and in a
      CD5+ B-cell line. These data suggest that a potential oncogene located near the
      2p13 breakpoint may have been activated by the t(2;14) translocation in these two
      cases of chronic lymphocytic leukemia.

PMID- 1373882
TI  - The promoter of the human cystic fibrosis transmembrane conductance regulator
      gene directing SV40 T antigen expression induces malignant proliferation of
      ependymal cells in transgenic mice.
AB  - Transgenic mice bearing a human cystic fibrosis transmembrane conductance
      regulator (CFTR) promoter-SV40 T antigen fusion transgene were generated in order
      to localize in vivo the potential oncogenesis linked to the tissue-specific
      activity of the promoter for the CFTR gene. Surprisingly, the only site of tumors
      resulting from expression of the reporter onc gene was ependymal cells lining the
      brain ventricles. SV40 T antigen expression in these cells led to a consistent
      pathology in the first weeks of age: ependymoma and consequent hydrocephaly.
      Tumor-derived cell lines were established, characterized and shown to originate
      from SV40 T antigen-induced ependymoma. No pathological alterations were found in
      other organs, such as lungs and pancreas, in which cystic fibrosis is
      pathologically manifest in humans. Such transgenic mice and derived cell lines
      may represent valid models for analysing (1) the role of SV40 T antigen in
      ependymoma formation and (2) CFTR function in ependymal cells.

PMID- 1373881
TI  - Detection of both mutant and wild-type p53 protein in normal skin fibroblasts and
      demonstration of a shared 'second hit' on p53 in diverse tumors from a cancer
      prone family with Li-Fraumeni syndrome.
AB  - Germline transmission of mutant p53 gene in cancer-prone families with Li
      Fraumeni syndrome has revealed a new role for p53 in the genetic predisposition
      to cancer. The studies reported here focus on the analysis of the expression of
      normal and mutant p53 RNA and protein in germline configuration and demonstrate
      that normal skin fibroblasts derived from members of a family with Li-Fraumeni
      syndrome express mutant p53Gly----Asp(245) protein and RNA at levels similar to
      the wild-type p53. Thus, these fibroblasts represent a unique biological system
      in which endogenous promoters are utilized for the expression of both mutant and
      normal p53. We have further extended the earlier observations on the analysis of
      mutant p53 with a limited number of tumors derived from individuals with Li
      Fraumeni syndrome. Tumors arising from two different germ layers in four
      individuals in a single family clearly exhibited the loss of the wild-type allele
      and the retention of the mutant allele observed in the normal skin fibroblasts
      derived from the same individuals. These observations further support the notion
      that germline p53 mutation plays a key role in the tumorigenesis of individuals
      with Li-Fraumeni syndrome.

PMID- 1373883
TI  - Temporal variation in the carbohydrate and peptide surface epitopes in antibody
      dependent, eosinophil-mediated killing of Schistosoma mansoni schistosomula.
AB  - Changes in the surface antigenicity and susceptibility to eosinophil-dependent
      killing during in vitro development of schistosomula of Schistosoma mansoni, were
      examined using sera from rabbits and mice immunized with antigens that are shed
      from the schistosomulum in vitro (shed antigen), a carbohydrate extract of shed
      antigen (SAg/CHO) or a periodate-insensitive fraction of shed antigen (SAg/PEP).
      Anti-SAg/CHO antisera recognised mainly carbohydrate epitopes on the parasite
      surface, whilst anti-SAg/PEP antisera bound to periodate-insensitive, putative
      peptide, surface epitopes. Anti-SAg/PEP antibodies failed to recognise the
      surface of newly transformed schistosomula unless the parasite was first treated
      with sodium periodate, suggesting that these epitopes may be masked by periodate
      sensitive (i.e., carbohydrate) epitopes. There was an increase in anti-SAg/PEP
      antibody binding to the larval surface with age of the parasite in vitro; five
      day-old lung schistosomula were also recognised by anti-SAg/PEP antisera. In
      contrast, anti-SAg/CHO antibody binding declined with parasite age, and failed
      totally to recognise lung schistosomula. This change in epitope expression was
      reflected in eosinophil-dependent cytotoxicity assays, with anti-SAg/CHO antisera
      killing young larvae and anti-SAg/PEP antisera only killing older larvae. Lung
      worms were not killed by either antisera. The difference in epitopes recognised
      by the antisera was also reflected in the antigens identified by
      immunoprecipitation and SDS-PAGE.

PMID- 1373884
TI  - Analysis of the specificity of the salivary antigens of Ornithodoros erraticus
      for the purpose of serological detection of swine farms harbouring the parasite.
AB  - In Spain, considerable efforts are currently being devoted to the eradication of
      Ornithodoros erraticus from the swine farms harbouring this parasite, the
      European vector of African swine fever (ASF). However, to do so, a preliminary
      requirement is to determine on which farms it is present. Of all possible methods
      for discovering this, the only one feasible for large scale application is the
      serological detection of swine bearing anti-O. erraticus antibodies. To apply
      serology it was necessary to check the specificity of extracts from the salivary
      glands (SGE) from O. erraticus. For this, indirect ELISA, competitive ELISA and
      Western blot were used to assay the SGE from O. erraticus and their corresponding
      antisera against the SGE and respective antisera from 4 ixodidae, one mange mite,
      one louse and a mosquito. The results obtained show that only the anti-ixodidae
      sera are able to react against the SGE from O. erraticus. The cause of this
      reaction are the somatic antigens present in the SGE of the argasid but not its
      soluble (secretory) antigens. It is proposed that the anti-cement antibodies
      present in the anti-ixodidae sera are those that react with the somatic antigens
      of O. erraticus.

PMID- 1373885
TI  - Human surfactant protein-A contains blood group A antigenic determinants.
AB  - A major blood group antigenic epitope was identified on human pulmonary
      surfactant protein A (SP-A). MAb and polyclonal antibodies generated against
      purified human SP-A aggregated blood group A human erythrocytes and immunostained
      epithelial cells in a variety of human tissues, consistent with the tissue
      distribution of major blood group antigens. SP-A MAb (MAb-8) agglutinated red
      cells and immunostained tissues from A or AB blood groups, but did not react with
      cells or tissues from O or B individuals. MAb-8 immunostaining of tissue from
      blood group A individuals was ablated by incubation with blood group A red cells.
      MAb and polyclonal antibodies directed against A blood group antigens reacted
      strongly with purified SP-A obtained from a blood group A individual with
      alveolar proteinosis. MAb and polyclonal antibodies specific for B blood group
      antigen failed to react with SP-A from this patient or from patients who were in
      blood group B. Reactivity of anti-blood group MAb was lost after treatment of SP
      A with endoglycosidase-F, demonstrating its reactivity with an epitope dependent
      on the asparagine-linked oligosaccharide at asparagine 187. Reactivity of MAb-8
      with SP-A persisted after endoglycosidase-F treatment, but was lost after
      digestion with collagenase as assessed by Western blot after SDS-PAGE. Reactivity
      of MAb to SP-A was sensitive to beta-elimination, supporting the presence of
      another blood group antigenic site distinct from the epitope dependent on the
      asparagine-linked carbohydrate. The finding that the SP-A molecule contains a
      major blood group epitope has implication for the clinical use of surfactant
      replacement preparations and diagnostic reagents based on this protein.

PMID- 1373886
TI  - Thrombin inhibition is impaired in plasma of sick neonates.
AB  - The sick neonate may develop spontaneous or catheter-related thromboses, which
      must in part reflect poor regulation of the formation and activities of the
      coagulation enzyme, thrombin. We hypothesized that the balance between the
      generation and inhibition of thrombin may differ in sick neonates compared with
      healthy neonates. Fifty neonates with respiratory failure requiring mechanical
      ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had
      normal coagulation screening tests and a platelet count greater than 150 x
      10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth
      weight, and health status were prepared. Eight plasma pools from 40 healthy
      neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates
      of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of
      GA less than 30 wk were studied. Thrombin generation was measured by amidolysis
      of a chromogenic substrate, S2238, after defibrination, contact activation, and
      recalcification of the test plasmas. The contributions of antithrombin III,
      heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin
      were quantitated by SDS-PAGE followed by autoradiography and densitometry.
      Thrombin generation was similar for both healthy and sick neonates of GA 30-38
      wk. However, the inhibition of thrombin was impaired in plasma from sick neonates
      of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/
      0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1373887
TI  - Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and
      cyclosporin A.
AB  - The immunosuppressive agents cyclosporin A (CsA) and FK 506 bind to distinct
      families of intracellular proteins (immunophilins) termed cyclophilins and FK 506
      binding proteins (FKBPs). Recently, it has been shown that, in vitro, the
      complexes of CsA-cyclophilin and FK 506-FKBP-12 bind to and inhibit the activity
      of calcineurin, a calcium-dependent serine/threonine phosphatase. We have
      investigated the effects of drug treatment on phosphatase activity in T
      lymphocytes. Calcineurin is expressed in T cells, and its activity can be
      measured in cell lysates. Both CsA and FK 506 specifically inhibit cellular
      calcineurin at drug concentrations that inhibit interleukin 2 production in
      activated T cells. Rapamycin, which binds to FKBPs but exhibits different
      biological activities than FK 506, has no effect on calcineurin activity.
      Furthermore, excess concentrations of rapamycin prevent the effects of FK 506,
      apparently by displacing FK 506 from FKBPs. These results show that calcineurin
      is a target of drug-immunophilin complexes in vivo and establish a physiological
      role for calcineurin in T-cell activation.

PMID- 1373888
TI  - Plus and minus RNAs of peach latent mosaic viroid self-cleave in vitro via
      hammerhead structures.
AB  - Peach latent mosaic viroid (PLMVd), the causal agent of peach latent mosaic
      disease, has been sequenced and found to be a circular RNA molecule of 337
      nucleotide residues, which adopts a branched conformation when it is folded in
      the model of lowest free energy. PLMVd exhibits limited homologies with other
      viroids and some satellite RNAs, but it does not have any of the central
      conserved sequences characteristic of the subgroups of typical viroids. However,
      a segment of approximately one-third of the PLMVd sequence has the elements
      required to form in the RNAs of both polarities the hammerhead structures
      proposed to act in the in vitro self-cleavage of avocado sunblotch viroid (ASBVd)
      and some satellite RNAs. Plus and minus partial- and full-length RNA transcripts
      of PLMVd containing the hammerhead structures displayed self-cleavage during
      transcription and after purification as predicted by these structures. These data
      are consistent with the high stability of the PLMVd hammerhead structures, more
      similar to the corresponding structures of some satellite RNAs than to those of
      ASBVd, and indicate that the self-cleavage reactions of PLMVd are most probably
      mediated by single hammerhead structures. Our results support the inclusion of
      PLMVd in a viroid subgroup represented by ASBVd, whose members are characterized
      by their ability to self-cleave in vitro, and probably in vivo, through
      hammerhead structures. A consensus phylogenetic tree has been obtained suggesting
      that PLMVd, together with ASBVd, may represent an evolutionary link between
      viroids and viroid-like satellite RNAs.

PMID- 1373889
TI  - Phage display of ricin B chain and its single binding domains: system for
      screening galactose-binding mutants.
AB  - We demonstrate that the B chain of ricin toxin preserves its lectin activity when
      expressed as a fusion protein on the surface of fd phage. Moreover, B chain,
      which folds into two topologically similar globular domains, can be dissected
      into amino-terminal and carboxyl-terminal domains to form single binding domains
      (SBDs) of B chain, each of which displays specificity for complex galactosides.
      The specific binding exhibited by the fusion protein of these SBDs was eliminated
      when amino acid substitutions Gly-46 in SBD1 or Gly-255 in SBD2 for native
      asparagine were introduced to alter key residues implicated in hydrogen bonding
      with substrate. These data demonstrate that it is possible to use a prokaryotic
      expression system to stably express and screen ricin B chain and its SBDs for
      sugar-binding mutants. Expression of ricin B chain on the surface of fd phage
      provides a method that can be used to efficiently select mutants with altered
      binding activities from a randomly generated library.

PMID- 1373890
TI  - Human linear B-cell epitopes encoded by the hepatitis E virus include
      determinants in the RNA-dependent RNA polymerase.
AB  - Hepatitis E virus is responsible for both sporadic and epidemic hepatitis in
      developing countries. The nonenveloped virus is 27-34 nm in diameter and has been
      shown to contain a single-strand, positive-sense, polyadenylylated RNA genome of
      approximately 7.5 kilobases. The nucleotide sequence of the Burma strain of
      hepatitis E virus has been reported and three open reading frames (ORFs) have
      been identified. The deduced amino acid sequence from each of these ORFs was used
      to synthesize overlapping peptides (decamers overlapping at every fourth amino
      acid) on a solid phase. These peptides were then tested in an ELISA with pooled
      acute-phase sera from known cases of enterically transmitted non-A, non-B
      hepatitis collected in the Sudan. Linear B-cell epitopes were identified in all
      three ORFs. Epitopes were identified throughout the polyprotein encoded by ORF1,
      but they appeared to be particularly concentrated in the region of the RNA
      dependent RNA polymerase. Distinct epitopes were identified in the presumed
      structural protein encoded by ORF2, and one epitope was identified close to the
      carboxyl terminus of the protein encoded by ORF3. These data precisely pinpoint
      linear B-cell epitopes recognized by antibodies from patients with acute
      hepatitis E and identify an antibody response directed against the RNA-dependent
      RNA polymerase.

PMID- 1373891
TI  - The gene for a tRNA modifying enzyme, m5U54-methyltransferase, is essential for
      viability in Escherichia coli.
AB  - One of the most abundant modified nucleosides in tRNA is 5-methyluridine (m5U or
      rT, ribothymidine). The enzyme tRNA(m5U54)methyltransferase [S-adenosyl-L
      methionine:tRNA (uracil-5-)-methyltransferase, EC 2.1.1.35] (the trmA gene
      product) catalyzes S-adenosylmethionine-dependent methylation of the uracil in
      position 54 (T psi C loop) in all Escherichia coli tRNAs to form m5U. Hitherto no
      modified nucleoside in tRNA has been shown to be essential for growth, although
      their importance in fine tuning the function of tRNA is well established. In this
      paper, we show that the structural gene trmA is essential for viability, although
      the known catalytic activity of the tRNA(m5U54)methyltransferase is not.

PMID- 1373892
TI  - Growth factor requirements for survival in G0 and entry into the cell cycle of
      primitive human hemopoietic progenitors.
AB  - In this study we have isolated populations of dormant human hemopoietic
      progenitors by two different approaches. First CD34+ cells isolated by panning
      were further separated on the basis of absence of HLA-DR expression by using
      fluorescence-activated cell sorting. Second, CD34+ HLA-DR- cells were isolated by
      nonadherence to soybean agglutinin, negative immunomagnetic bead selection with
      lineage-specific antibodies, and two-color cell sorting. Progenitors in either
      cell population were unable to form colonies in the presence of interleukin (IL)
      3 alone but yielded a substantial number of colonies, including multilineage
      colonies, in the presence of combinations of IL-3 and IL-6. Similarly, IL-3 plus
      any one of the other synergistic factors, including granulocyte colony
      stimulating factor, IL-11, leukemia inhibitory factor, and steel factor,
      effectively supported colony formation from CD34+ HLA-DR- progenitors. Sequential
      observation of colony formation from single CD34+ HLA-DR- cells provided
      definitive evidence that the synergistic factors trigger cell divisions of
      dormant cells. Studies with delayed addition of factors to the cultures provided
      evidence that this population of cells also requires IL-3 or
      granulocyte/macrophage colony-stimulating factor (GM-CSF) to survive even while
      dormant. In contrast, none of the synergistic factors were able to replace IL-3
      or GM-CSF in this function. These findings confirm and extend the model that
      multiple factors with overlapping functions operate both independently and in
      combination to regulate early stages of hemopoiesis.

PMID- 1373893
TI  - Integration of cytoplasmic calcium and membrane potential oscillations maintains
      calcium signaling in pituitary gonadotrophs.
AB  - Pituitary gonadotrophs exhibit spontaneous low-amplitude fluctuations in
      cytoplasmic calcium concentration ([Ca2+]i) due to intermittent firing of
      nifedipine-sensitive action potentials. The hypothalamic neuropeptide,
      gonadotropin-releasing hormone, terminates such spontaneous [Ca2+]i transients
      and plasma-membrane electrical activity and initiates high-amplitude [Ca2+]i
      oscillations and concomitant oscillations in membrane potential (Vm). The onset
      of agonist-induced [Ca2+]i oscillations is not dependent on Vm or extracellular
      Ca2+ but is associated with plasma-membrane hyperpolarization interrupted by
      regular waves of depolarization with firing of action potentials at the peak of
      each wave. The Vm and Ca2+ oscillations are interdependent during continued
      gonadotropin-releasing hormone action (greater than 3-5 min), when sustained Ca2+
      entry is necessary for the maintenance of [Ca2+]i spiking. The initial and
      sustained agonist-induced Ca2+ transients and Vm oscillations are abolished by
      blockade of endoplasmic reticulum Ca(2+)-ATPase, consistent with the role of Ca2+
      re-uptake by internal stores in the oscillatory response during both phases. Such
      a pattern of synchronization of electrical activity and Ca2+ spiking in cells
      regulated by Ca(2+)-mobilizing receptors shows that the operation of the
      cytoplasmic oscillator can be integrated with a plasma-membrane oscillator to
      provide a long-lasting signal during sustained agonist stimulation.

PMID- 1373894
TI  - Growth characteristics and expansion of human umbilical cord blood and estimation
      of its potential for transplantation in adults.
AB  - We estimated whether single collections of cord blood contained sufficient cells
      for hematopoietic engraftment of adults by evaluating numbers of cord blood and
      adult bone marrow myeloid progenitor cells (MPCs) as detected in vitro with steel
      factor (SLF) and hematopoietic colony-stimulating factors (CSFs). SLF plus
      granulocyte-macrophage (GM)-CSF detected 8- to 11-fold more cord blood GM
      progenitors [colony-forming units (CFU)-GM] than cells stimulated with GM-CSF or
      5637 conditioned medium (CM), growth factors previously used to estimate cord
      blood CFU-GM numbers. SLF plus erythropoietin (Epo) plus interleukin 3 (IL-3)
      enhanced detection of cord blood multipotential (CFU-GEMM) progenitors 15-fold
      compared to stimulation with Epo plus IL-3. Under the same conditions, bone
      marrow CFU-GM and CFU-GEMM were only enhanced in detection 2- to 4- and 6- to 8
      fold. Increased detection of cord blood CFU-GEMM correlated directly with
      decreased detection of cord blood erythroid burst-forming units (BFU-E). In
      contrast, adult bone marrow CFU-GEMM and BFU-E numbers were both enhanced by SLF
      plus Epo plus IL-3. This suggests that most cord blood BFU-E may actually be CFU
      GEMM. Cord blood collections (n = 17) contained numbers of MPCs (especially CFU
      GM) similar to the number found in nine autologous bone marrow collections. To
      assess additional sources of MPCs, the peripheral blood of 1-day-old infants was
      assessed. However, average concentrations of MPCs circulating in these infants
      were only 30-46% that in their cord blood. Expansion of cord blood MPCs was also
      evaluated. Incubation of cord blood cells for 7 days with SLF resulted in 7.9-,
      2.2-, and 2.7-fold increases in numbers of CFU-GM, BFU-E, and CFU-GEMM compared
      to starting numbers; addition of a CSF with SLF resulted in even greater
      expansion of MPCs. The results suggest that cord blood contains a larger number
      of early profile MPCs than previously recognized and that there are probably
      sufficient numbers of cells in a single cord blood collection to engraft an
      adult. Although the expansion data must be considered with caution, as human
      marrow repopulating cells cannot be assessed directly, in vitro expansion of cord
      blood stem and progenitor cells may be feasible for clinical transplantation.

PMID- 1373895
TI  - Mutation in the primer binding site of the type 1 human immunodeficiency virus
      genome affects virus production and infectivity.
AB  - In an effort to understand the contribution of the primer-binding site (PBS)
      region to human immunodeficiency virus (HIV) replication, we have constructed a
      mutant HIV proviral DNA with an alteration in the 5' end of the PBS. The PBS
      mutant proviral DNA was characterized by transfection of the viral DNA into CD4+
      and non-CD4+ target cells. The results indicate that mutation in the PBS reduced
      the level of viral particles released into the medium of transfected cells in
      comparison to wild-type proviral DNA. The viral particles were noninfectious upon
      transmission to established CD4+ cell lines and phytohemagglutinin-stimulated
      peripheral blood lymphocytes. Electron microscopic analysis of the transfected
      cells revealed no abnormalities in the structure of the virion directed by the
      mutant proviral DNA. Also, the protein and RNA contents of the mutant virions
      were similar to the wild type. The quantitation of intracellular viral structural
      protein in the transfected cells, however, indicated that the PBS mutation may
      have an effect on the assembly of viral particles in addition to completely
      abolishing reverse transcription of viral RNA into DNA. These results provide
      evidence that the PBS region of the viral genome has multiple functions in HIV-1
      replication.

PMID- 1373896
TI  - Expression and function of the murine B7 antigen, the major costimulatory
      molecule expressed by peritoneal exudate cells.
AB  - The murine B7 (mB7) protein is a potent costimulatory molecule for the T-cell
      receptor (TCR)-mediated activation of murine CD4+ T cells. We have previously
      shown that stable mB7-transfected Chinese hamster ovary (CHO) cells but not
      vector-transfected controls synergize with either anti-CD3 monoclonal antibody
      induced or concanavalin A-induced T-cell activation, resulting ultimately in
      lymphokine production and proliferation. We now have generated a hamster anti-mB7
      monoclonal antibody. This reagent recognizes a protein with an apparent molecular
      mass of 50-60 kDa. The mB7 antigen is expressed on activated B cells and on
      peritoneal exudate cells (PECs). Antibody blocking experiments demonstrate that
      mB7 is the major costimulatory molecule expressed by PECs for the activation of
      murine CD4+ T cells. This suggests an important role for mB7 during immune-cell
      interactions. We have also surveyed a panel of murine cell lines capable of
      providing costimulatory activity. Our results indicate that mB7 is the major
      costimulatory molecule on some but not all cell lines and that there may be
      additional molecules besides mB7 that can costimulate the activation of murine
      CD4+ T cells.

PMID- 1373897
TI  - RNA/nucleotide enhances antibody production in vitro and is moderately mitogenic
      to murine spleen lymphocytes.
AB  - Suppression of immune functions was demonstrated in both humans and animals when
      exogenous RNA was eliminated from the diet. However, direct actions of
      RNA/nucleotide on the immune system are virtually unknown. Thus, in this study,
      we explored effects of RNA and nucleotide on lymphocyte functions in vitro. Yeast
      whole RNA, which is free of endotoxin, was supplemented to culture media, and
      changes in mitogen responses, thymocyte proliferation, or in vitro antibody
      production by murine spleen lymphocytes were analyzed. Yeast whole RNA
      potentiated the proliferation of spleen lymphocytes and it also strikingly
      enhanced in vitro antibody production in response to sheep red blood cells at
      least 10-fold. However, it did not potentiate the proliferation of thymocytes
      (immature lymphocytes). These enhancing activities of yeast RNA were
      significantly reduced by RNAse treatment, but not by treatments with DNAse or
      polymyxin B. Certain mononucleotides exhibited less, but similar, action on
      murine spleen lymphocytes. The whole yeast RNA employed was already degraded to
      small nucleotide (less than 1 kb). Therefore, it may be suggested that certain
      components of RNA degraders can function as powerful immunomodulators, indicating
      that exogenous RNA or nucleotide may be important in facilitating immune
      responses under certain circumstances.

PMID- 1373898
TI  - Role of interferons in maternal recognition of pregnancy in ruminants.
AB  - It has recently become evident that a type I interferon (IFN) subtype signals the
      presence of a viable conceptus to the mother during early pregnancy in cattle,
      sheep, and related mammalian species. This IFN, which is a product of the
      epithelium (trophectoderm) of the expanding trophoblast, is expressed in
      extremely large quantities for a few days just prior to implantation. It appears
      to be involved in modulating the release of the luteolytic hormone, prostaglandin
      F2 alpha, from the uterine endometrium and, hence, preventing the destruction of
      the corpus luteum that normally occurs at the end of an estrous cycle if an egg
      has not been fertilized. These trophoblast IFN have antiviral, antiproliferative,
      and immunomodulatory properties quite similar to other type I IFN, such as IFN
      alpha, -beta, and -omega. However, they constitute a structurally and
      serologically distinct subtype. In addition, they are poorly inducible by virus,
      and the promoter regions of their genes are organized differently than other type
      I IFN. The genes for these trophoblast IFN are confined to ruminant species in
      the Artiodactyla order and probably evolved from IFN-omega less than 55 million
      years ago. There is no evidence for comparable production of type I IFN by
      trophoblast and placental tissues of mammals outside this ruminant group. Recent
      experiments have indicated that IFN treatment may have value in improving
      reproductive performance of sheep when provided during the period of maternal
      recognition of pregnancy, when much embryonic loss is believed to occur.

PMID- 1373899
TI  - Renal reabsorptive capacity for alpha 2u-globulin in the adult male rat.
AB  - Adult male rats were maintained on 0, 5, 10, 15, and 20% casein diets to produce
      a series of animals having serum alpha 2u-globulin levels varying linearly from a
      normal of 31 micrograms/ml to a minimum of 13 micrograms/ml. In this way, it was
      possible to titrate endogenously the renal reabsorption and urinary excretion of
      this low molecular weight protein. The average maximal reabsorption rate (Tm) was
      established to be 9.7 micrograms/min and was reached at a renal filtered load (F
      alpha 2u) of 13.6 micrograms/min. These data were expressed in terms of a Tm:F
      alpha 2u ratio of 0.71. Below this value, the reabsorption declined from 70% to
      50% of the F alpha 2u. Above 0.71, where F alpha 2u is less than the Tm, the
      reabsorption increased to 80-90%. It was observed that the fractional renal
      uptake of the alpha 2u-globulin varied linearly with the filtered load.

PMID- 1373900
TI  - Ca(2+)-induced translocation of protein kinase C during Ca(2+)-dependent
      histamine release from beta-escin-permeabilized rat mast cells.
AB  - When rat mast cells were cultured for a short period in plastic dishes and
      adhering cells were permeabilized with beta-escin and exposed to Ca2+ at
      concentrations higher than 10(-7) mol/l, histamine release was induced dose
      dependently. Protein kinase C (PKC) activity in the crude extracts obtained from
      adhering mast cells was induced in the presence of Ca2+, phospholipid and
      diacylglycerol. The apparent Km value of PKC for Ca2+ was 0.33 mumol/l, and this
      Ca2+ concentration was equivalent to that which can elicit half the maximum of
      the Ca(2+0-induced histamine release. After permeabilization, approximately 80%
      of the total PKC activity remained in the cytosolic fraction. In the resting
      state, 95% of the total PKC activity was detected in the soluble fraction, and
      the rest was detected in the membrane fraction. When permeabilized mast cells
      were incubated with Ca2+ at micromolar concentrations, which are effective in
      releasing histamine, the total PKC activity did not change. However, the
      translocation of PKC took place from the cytosolic fraction to the membrane
      fraction, corresponding to Ca2+ concentrations in the medium. When the crude PKC
      extract of mast cells was incubated with phospholipid vesicles and centrifuged,
      the PKC activity in the supernatant was diminished; the amount of PKC binding to
      the vesicles was dependent upon Ca2+ concentrations in the medium. Calphostin C,
      a potent PKC inhibitor, interacts with PKC in a noncompetitive manner, and it
      does not inhibit Ca(2+)-induced translocation of PKC. It can be concluded that
      PKC is translocated into the cell membrane along with an increase in
      intracellular Ca2+ concentrations and the subsequent activation of PKC may be
      crucial for the process leading to histamine release.

PMID- 1373901
TI  - Calcium channel agonist/antagonist effects on cholinergic stimulation of the
      diabetic rat bladder.
AB  - The in vitro effects of a calcium channel agonist (BAY K8644) and antagonist
      (nifedipine) on the cholinergic responses of the streptozotocin-induced diabetic
      rat bladder were investigated. the bladder body and bladder base were studied
      separately. There were significant differences in contractile responses to
      acetylcholine stimulation in the diabetic bladder body compared to the control
      body. Similarly, the diabetic bladder base demonstrated significantly increased
      contractile responses compared to the control base. Contractile responses in the
      diabetic bladder body and base were significantly increased from the control in
      the absence of extracellular calcium. Differences were found in the effects on
      maximum responses between diabetic and control tissues treated with nifedipine
      and BAY K8644. BAY K8644 did not completely reverse the effect of nifedipine on
      the contractile responses. Rates of contractile response were significantly
      different between controls and diabetics and between body and base. Alterations
      in calcium channel activity in diabetic bladder smooth muscle may be responsible
      at least in part for the nonspecific pharmacologic responses found in smooth
      muscle strips.

PMID- 1373902
TI  - Examination for lipid peroxidation in liver microsomes of guinea pigs as a causal
      factor in the decrease in the content of cytochrome P-450 due to ascorbic acid
      deficiency.
AB  - The content of cytochrome P-450 in liver microsomes from guinea pigs was
      decreased by ascorbic acid-deficiency. Since ascorbic acid is an antioxidant in
      vivo, the possible involvement of lipid peroxidation in this phenomenon was
      investigated. In fact, the level of lipid peroxides in liver homogenates of
      guinea pigs was increased by ascorbic acid deficiency. The level was
      significantly decreased when the animals were given tocopherol acetate (25
      mg/kg/day, s.c.) with an ascorbic acid-free diet. The activities of aminopyrine N
      demethylase, aniline hydroxylase, p-nitroanisole O-demethylase and 7
      ethoxycoumarin O-deethylase, and the content of cytochrome P-450 spectrally
      determined did not restore the control level by the administration of tocopherol
      acetate to the ascorbic acid-deficient animals. Western blot analysis of liver
      microsomes with antibodies to rat P-450IA2 (P-448-H), P-450IIB1 (P-450b) and
      human P-450IIIA4 (P-450NF) showed that ascorbic acid-deficiency resulted in a
      decrease in the amount of cytochrome P-450 immunochemically related to P-450IA2,
      but not the amounts of the forms of cytochrome P-450 cross-reactive with
      antibodies to P-450IIB1 and P-450IIIA4. The reduced amounts of cytochrome P-450
      cross-reactive with antibodies to rat P-450IA2 in liver microsomes of ascorbic
      acid-deficient animals remained unchanged even when lipid peroxidation was
      inhibited by tocopherol acetate, suggesting that there is a mechanism(s) other
      than lipid peroxidation involved in the reduction of amounts of cytochrome P-450
      by ascorbic acid deficiency.

PMID- 1373903
TI  - [The thoracic outlet: true syndromes, disputed syndrome (TOS, thoracic outlet
      syndrome). Current status 1991].
AB  - There are 5 syndromes involving the thoracic outlet. The first four, although not
      well known, especially the first two, are authentic; they are: 1) arterial, due
      to a well formed cervical rib or to an incompletely formed first rib; 2)
      neurological, related to the fibrous band associated with a rudimentary cervical
      rib or a giant transverse process of C7; 3) venous, namely "effort thrombosis";
      4) late post-traumatic, secondary to a fracture of the clavicle. The study of
      these four syndromes prepares the reader to that of the controversial fifth
      syndrome, which is entirely subjective, made only of symptoms. The fifth
      syndrome, by very far the most frequent in the literature, called "scalenus
      anticus syndrome" in the past, now called "thoracic outlet syndrome" or "TOS" by
      North-American authors, has two varieties, one where hypotonic shoulder muscles,
      mostly in women, respond well to specific and simple exercises, and one where
      there is an accident in the background, a whiplash type of injury in most cases.
      Despite the fact that TOS is made only of symptoms, "diagnosing" it has led to
      scores of operations, scalenotomy in the past, now mostly resection of the first
      rib, sometimes scalenectomy. Huge surgical statistics, that deal mostly with
      resection of the first rib, have not proven the authenticity of this second
      variety of the 5th syndrome. Surgeons report only early surgical results, and the
      results claimed are invariably impressive. Never is there a statistic about
      return to work after surgery. First rib resection can be dangerous and it can be
      complicated by tardy permanent brachial plexopathy. One very recent European
      study proves the discrepancy between the early appreciation of the results by the
      surgeon and the late appreciation by independent observers.

PMID- 1373905
TI  - Novel function discovered for the cystic fibrosis gene.

PMID- 1373904
TI  - Relationship between neuropeptide immunoreactive nerves and inflammatory cells in
      adjuvant arthritic rats.
AB  - The purpose of this study was to assess the relationship of neuropeptide nerves
      and inflammatory leukocytes in PVG rats with adjuvant-induced arthritis.
      Substance P- and calcitonin gene-related peptide (CGRP)-immunoreactive nerves and
      inflammatory leukocytes were studied, using peroxidase (ABC) and/or alkaline
      phosphatase (APAAP) staining. Inflamed synovial tissue proper was infiltrated
      with neutrophils, ED1 macrophages and focal accumulations of CD2 T lymphocytes.
      In such tissue, the relationship between peptide-immunoreactive nerves and
      inflammatory cells was such that substance P and CGRP nerves were absent in
      heavily infiltrated villous synovial tissue, whereas healthy synovial tissue and
      non-inflammatory areas in adjuvant arthritic rats were innervated by substance P
      and CGRP nerves close to normal synovial tissue resident cells. In order to
      elucidate an eventual mechanism for lost immunoreactivity, healthy synovial
      tissue was exposed to chymotrypsin or oxygen derived free radicals (ODFR) in
      vitro. The former treatment caused total loss of immunoreactivity. These findings
      suggest that neuropeptides and neuropeptide containing nerves may be destroyed by
      locally produced proteolytic enzymes and various reactive oxygen species in the
      vicinity of inflammatory cells.

PMID- 1373906
TI  - Ion channels for communication between and within cells.

PMID- 1373907
TI  - Elementary steps in synaptic transmission revealed by currents through single ion
      channels.

PMID- 1373908
TI  - Regulation of plasma membrane recycling by CFTR.
AB  - The gene that encodes the cystic fibrosis transmembrane conductance regulator
      (CFTR) is defective in patients with cystic fibrosis. Although the protein
      product of the CFTR gene has been proposed to function as a chloride ion channel,
      certain aspects of its function remain unclear. The role of CFTR in the adenosine
      3',5'-monophosphate (cAMP)-dependent regulation of plasma membrane recycling was
      examined. Adenosine 3',5'-monophosphate is known to regulate endocytosis and
      exocytosis in chloride-secreting epithelial cells that express CFTR. However,
      mutant epithelial cells derived from a patient with cystic fibrosis exhibited no
      cAMP-dependent regulation of endocytosis and exocytosis until they were
      transfected with complementary DNA encoding wild-type CFTR. Thus, CFTR is
      critical for cAMP-dependent regulation of membrane recycling in epithelial
      tissues, and this function of CFTR could explain in part the pleiotropic nature
      of cystic fibrosis.

PMID- 1373909
TI  - Regulation of arterial tone by activation of calcium-dependent potassium
      channels.
AB  - Blood pressure and tissue perfusion are controlled in part by the level of
      intrinsic (myogenic) vascular tone. However, many of the molecular determinants
      of this response are unknown. Evidence is now presented that the degree of
      myogenic tone is regulated in part by the activation of large-conductance calcium
      activated potassium channels in arterial smooth muscle. Tetraethylammonium ion
      (TEA+) and charybdotoxin (CTX), at concentrations that block calcium-activated
      potassium channels in smooth muscle cells isolated from cerebral arteries,
      depolarized and constricted pressurized cerebral arteries with myogenic tone.
      Both TEA+ and CTX had little effect on arteries when intracellular calcium was
      reduced by lowering intravascular pressure or by blocking calcium channels.
      Elevation of intravascular pressure through membrane depolarization and an
      increase in intracellular calcium may activate calcium-activated potassium
      channels. Thus, these channels may serve as a negative feedback pathway to
      control the degree of membrane depolarization and vasoconstriction.

PMID- 1373911
TI  - Expression of collagenase and potential transcriptional factors in the MRL/l
      mouse arthropathy.
AB  - Typical erosions of articular joint structures in rheumatoid arthritis and in the
      spontaneous destructive hind-limb arthropathy of autoimmune MRL-lpr/lpr (MRL/l)
      mice occur predominantly in areas contiguous with proliferating synovial lining
      cells, suggesting release of proteolytic enzymes from these cells. Synovial
      lining cells were isolated from arthritic MRL/l mice, and the spontaneous
      expression of the interstitial procollagenase and its potential transcriptional
      factors, egr-1 and c-fos, was examined in vitro. The data indicate that basal
      collagenase RNA expression was stronger in MRL/l cells than in virus-transformed
      cells. Moreover, elevated RNA levels of the c-fos gene could be detected in the
      collagenase-expressing synovial lining cells in vitro. In a related
      immunohistochemical study, collagenase was detected in situ in proliferating
      synovial lining cells as well as in chondrocytes of the first stage of
      pathological changes in the MRL/l mouse arthropathy.

PMID- 1373910
TI  - Isolation of a complementary DNA that encodes the mammalian splicing factor SC35.
AB  - The mammalian splicing factor SC35 is required for the first step in the splicing
      reaction and for spliceosome assembly. The cloning and characterization of a
      complementary DNA encoding this protein revealed that it is a member of a family
      of splicing factors that includes mammalian SF2/ASF. This family of proteins is
      characterized by the presence of a ribonucleoprotein (RNP)-type RNA binding motif
      and a carboxyl-terminal serine-arginine-rich (SR) domain. A search of the DNA
      sequence database revealed that the thymus-specific exon (ET) of the c-myb proto
      oncogene is encoded on the antisense strand of the SC35 gene.

PMID- 1373912
TI  - Are lymphocytes a target for substance P modulation in arthritis?
AB  - The contribution of the neuropeptide substance P to the pathogenesis of
      rheumatoid arthritis (RA) has recently been suggested. The presence of
      immunoreactive substance P in the serum and joint fluid of RA patients was
      significantly increased compared with age-matched control patients. To
      investigate the ability of substance P to alter lymphocyte activity during the
      disease, lymphocytes were isolated from the synovial fluid and blood of RA
      patients and their ability to respond to substance P as measured by [3H]thymidine
      uptake was characterized. Upon exposure of RA synovial fluid and peripheral blood
      lymphocytes to various concentrations of substance P in vitro, no increase in
      proliferation was witnessed. To the contrary, control peripheral blood lymphocyte
      proliferation was significantly enhanced by various concentrations of substance
      P. However, synoviocytes from the joints of RA patients were responsive to
      substance P stimulation. These data suggest that substance P receptors may be
      desensitized on systemic and local lymphocytes in RA, or the proinflammatory
      activities of substance P may be mediated via the synovial membrane during
      chronic inflammation.

PMID- 1373913
TI  - [Metastasis and markers].
AB  - Tumor markers are antigens which can be associated with certain malignancies. A
      variety of markers have been demonstrated in genitourinary tumors. The best known
      examples are human chorionic gonadotropin (bHCG) and alpha-fetoprotein (AFP) for
      testicular tumors, prostatic acid phosphatase (PAP) and prostatic specific
      antigen (PSA) for prostatic cancer. The plasma levels of these substances are
      influenced by the tumor mass and therefore by the tumor stage. Markedly elevated
      plasma levels can be demonstrated when metastases are present, although a few
      patients without metastases may elaborate abnormal amount of markers. The removal
      of the primary tumor leads to a fall to normal levels: a still increased level
      indicates residual primary tumor or the presence of metastases. Measurements of
      markers are also of value in estimating the effects of medical treatment and in
      detecting local or distant recurrences.

PMID- 1373914
TI  - [Radiotherapy in the control of bone metastases in patients with adenocarcinoma
      of the prostate].
AB  - Advanced prostatic carcinoma shows a high incidence of bone metastases. This is
      the main cause of clinical problems such as invalidating bone fractions,
      collapses and consequently of sharp pain syndromes. In these cases the therapy
      needs to achieve quick relief of symptoms. Radiotherapy, with its large variety
      of technical options, allows a wide modulation to fit a lot of clinical
      situations among the most frequent for these patients. A large series of
      treatment modalities and related indications will be presented and discussed in
      this work.

PMID- 1373915
TI  - [Biochemical factors as objective parameters for assessing the prognosis in
      polytrauma].
AB  - One hundred patients with multiple injuries (mean ISS 37 patients) were
      prospectively evaluated over a period of 14 days following trauma. Significant
      differences in the blood levels of PMN elastase, cathepsin B, lactate, neopterin,
      C-reactive protein (CRP) and antithrombin III (ATIII) were found in non-survivors
      and in survivors with and without organ failure. On admission, a prediction of
      organ failure was possible with an accuracy of 63% to 69% (PMN elastase,
      cathepsin B, ATIII). Death was predictable with an 80% to 90% accuracy within the
      first 4 days (PMN elastase, lactate, CRP, neopterin). The prognostic value of
      these factors was comparable to trauma scores regarding organ failure and better
      with respect to death. Biochemical parameters may be helpful in estimating the
      severity of the injury and prognosis and in monitoring the ICU course of such
      patients.

PMID- 1373916
TI  - Maintenance immunosuppression after liver transplantation.

PMID- 1373917
TI  - Retinal regeneration.
AB  - The goal of research on neural regeneration is to restore brain function
      following injury. To many, this suggests regrowing damaged axons and re
      establishing the interrupted pathways. A second, but little studied aspect of
      brain regeneration, is the replacement of lost neurons. For example, in some
      animals the neural retina is reconstituted by regenerative neurogenesis following
      its partial or total destruction. Two separate processes underlying retinal
      regeneration have been described: transdifferentiation of retinal pigmented
      epithelial cells into retinal neural progenitors (in adult urodeles, tadpoles,
      and embryonic chickens), and alteration in the fate of photoreceptor progenitors
      intrinsic to the retina (in adult fish).

PMID- 1373918
TI  - Neurons that say NO.
AB  - Thirty years ago, Thomas and Pearse discovered what they termed 'solitary active
      cells'--neurons containing an unusually high nicotinamide adenine dinucleotide
      phosphate diaphorase (NADPH-diaphorase) activity that could be detected
      histochemically. Although these neurons were considered as something special, an
      appropriate mechanism to account for their outstanding metabolism was not
      provided until the recent identification of neuronal NADPH-diaphorase as nitric
      oxide synthase. This simple histochemical method now allows the precise
      anatomical localization of the neurons generating the exotic messenger molecule
      nitric oxide. This article reviews the functional implications that arise from
      our new knowledge of the anatomy of the nitric oxide signal transduction pathway
      in the nervous system. The widespread distribution of this system indicates that
      for those interested in cellular communication nitric oxide is a gas to study.

PMID- 1373919
TI  - Models of neuronal injury in AIDS: another role for the NMDA receptor?
AB  - As many as two-thirds of patients with acquired immunodeficiency syndrome (AIDS)
      eventually suffer from neurological manifestations, including dysfunction of
      cognition, movement and sensation. How can human immunodeficiency virus type 1
      (HIV-1) result in neuronal damage if neurons themselves are not infected by the
      virus? In this article Stuart Lipton reviews a series of experiments from several
      different laboratories that offer related hypotheses accounting for neurotoxicity
      in the brains of AIDS patients. There is growing support for the existence of HIV
      or immune-related toxins that directly or indirectly lead to the injury or
      demise of neurons via a potentially complex web of interactions between
      macrophages (or microglia), astrocytes and neurons. However, a final common
      pathway for neuronal susceptibility appears to be operative, similar to that
      observed after stroke, trauma and epilepsy. This mechanism involves voltage
      dependent Ca2+ channels and NMDA receptor-operated channels, and therefore offers
      hope for future pharmacological intervention.

PMID- 1373920
TI  - Dependence of postnatal motoneurones on their targets: review and hypothesis.
AB  - Motoneurones are known to die (1) during embryonic development (naturally
      occurring cell death), (2) early in postnatal development after axonal injury,
      and (3) as a consequence of disease, such as spinal muscular atrophy or (in later
      life) amyotrophic lateral sclerosis. Naturally occurring motoneurone death has
      been extensively investigated, and interaction with the target muscle has emerged
      as an important factor for survival of embryonic motoneurones. Evidence that this
      target dependence of motoneurones continues postnatally is discussed in this
      review, as is the possible nature of the retrograde signal from the muscle. An
      explanation for the role of the muscle in motoneurone survival is also proposed,
      which may be applicable in situations where motoneurone death occurs postnatally.
      This proposal takes into account the changing functional demands imposed on
      motoneurones as a result of the gradual maturation of the CNS, and suggests that
      during development the muscle induces the motoneurones to become competent to
      carry out these requirements.

PMID- 1373921
TI  - 'Traditional' pharmacotherapy may succeed in Alzheimer's disease.

PMID- 1373922
TI  - Dialysis or diffusion?

PMID- 1373923
TI  - The ON and OFF channels of the visual system.
AB  - In the vertebrate retina, all photoreceptors hyperpolarize in response to light.
      In the outer retina, at the bipolar cell level, a dual system is created from the
      cones forming the ON and OFF channels. In the rod system a similar arrangement is
      found, but the ON and OFF channels in many species are formed using an amacrine
      cell network in the inner retina. Physiological experiments in which the ON
      bipolar cells are pharmacologically blocked reveal that in the primate the two
      channels remain largely segregated in the geniculostriate system until they reach
      the cortex, where they converge upon single cells. Behavioral studies show that
      following ON channel block, notable deficits arise in the detection of light
      increments but not light decrements. These and related studies suggest that the
      ON and OFF channels optimize information transfer to the CNS by providing
      excitatory signals for both increases and decreases in light energy.

PMID- 1373924
TI  - Metabotropic receptors and 'slow' excitatory actions of glutamate agonists in the
      hippocampus.
AB  - The actions of glutamate in the CNS can be divided into ionotropic and
      metabotropic effects. The ionotropic receptors participate in synaptic
      transmission by directly opening nonselective cation channels. Recently, a so
      called 'metabotropic effect' of glutamate has been described and is attributed to
      a novel metabotropic glutamate receptor. This effect consists of increased
      hydrolysis of membrane phosphoinositides, production of the second messengers
      diacylglycerol and inositol 1,4,5-trisphosphate, and mobilization of
      intracellular Ca2+. Activation of metabotropic glutamate receptors blocks the
      slow Ca(2+)-dependent K+ conductance and increases the membrane excitability of
      neurones. In addition, metabotropic agonists block the excitatory synaptic
      transmission supported by the ionotropic glutamate receptor, and may therefore
      play a critical role in synaptic plasticity. However, intracellular mechanisms
      linking metabotropic glutamate receptors with ionic channels remain unclear. This
      article discusses recent findings concerning metabotropic agonist effects on
      membrane currents and synaptic transmission, the pharmacology of the agonists and
      the roles played by G proteins and second messengers in mediating their effects.

PMID- 1373925
TI  - Activity-dependent neuronal plasticity following tissue injury and inflammation.
AB  - Increases in neuronal activity in response to tissue injury lead to changes in
      gene expression and prolonged changes in the nervous system. These functional
      changes appear to contribute to the hyperalgesia and spontaneous pain associated
      with tissue injury. This activity-dependent plasticity involves neuropeptides,
      such as dynorphin, substance P and calcitonin gene-related peptide, and
      excitatory amino acids, such as NMDA, which are chemical mediators involved in
      nociceptive processing. Unilateral inflammation in the hindpaw of the rat results
      in an increase in the expression of preprodynorphin and preproenkephalin mRNA in
      the spinal cord, which parallels the behavioral hyperalgesia associated with the
      inflammation. Cellular intermediate-early genes, such as c-fos, are also
      expressed in spinal cord neurons following inflammation and activation of
      nociceptors. Peripheral inflammation results in an enlargement of the receptive
      fields of many of these neurons. Dynorphin applied to the spinal cord also
      induces an enlargement of receptive fields. NMDA antagonists block the
      hyperexcitability produced by inflammation. A model has been proposed in which
      dynorphin, substance P and calcitonin gene-related peptide enhance excitability
      at NMDA receptor sites, leading first to dorsal horn hyperexcitability and then
      to excessive depolarization and excitotoxicity.

PMID- 1373926
TI  - [Effect of low and high molecular weight dextrans on selected serum lipid
      parameters. 1].
AB  - Three male patients with hyperlipidaemia were given daily infusions of dextran
      over a period of 10 days. Plasma levels of total cholesterol, LDL and HDL
      cholesterol, apolipoprotein B and AI and triglycerides were analysed after the
      infusion of dextrans different in dose and molecular size. Dextrans caused
      alterations of some plasma lipids and lipoproteins exceeding the haemodilution
      effect. The degree of lipid lowering depends on the volume and molecular size of
      the administered dextran.

PMID- 1373927
TI  - Inhibitory influence of a new steroidal anti-androgen, TZP-4238, on prostatic
      hyperplasia in the beagle dog.
AB  - The effect of a synthetic steroidal anti-androgen, TZP-4238, on spontaneous
      benign prostatic hyperplasia (BPH) in dogs was investigated. Old male beagle dogs
      (5-9 years old) were divided into three experimental groups. Group 1 consisted of
      BPH controls. Groups 2 and 3 received TZP-4238 0.1 mg/kg/day and chlormadinone
      acetate (CMA) 0.3 mg/kg/day p.o., respectively, for 5 months. In group 1,
      glandular hyperplasia of the prostate was clearly detected. In contrast, TZP-4238
      (Group 2) or CMA (Group 3) produced marked atrophy of the glandular epithelium.
      In addition, a histopathological study showed that TZP-4238 or CMA medication for
      5 months exerted no effect on the testes and the pituitary luteinizing hormone
      (LH) cells. Therefore, it is suggested that TZP-4238 (0.1 mg/kg) or CMA (0.3
      mg/kg) causes regression of spontaneous canine BPH without any histopathological
      effects on the testes and pituitary LH cells. However, slightly decreased serum
      testosterone levels were found in TZP-4238-treated animals, due apparently to a
      direct and/or indirect effect on the testes. Thus, it is suggested that a
      marginal antigonadotrophic effect cannot be excluded. It is concluded that TZP
      4238 is a potent anti-androgen for the treatment of spontaneous canine BPH,
      without any negative influence on the function of the testes and the pituitary LH
      cells.

PMID- 1373928
TI  - Immunoreactivity of human tissue mast cells.

PMID- 1373929
TI  - Development and characterization of a rapidly proliferating, well-differentiated
      cell line derived from normal adult human osteoblast-like cells transfected with
      SV40 large T antigen.
AB  - A new bone cell line was established by transfecting normal adult human
      osteoblast-like (hOB) cells, derived from a 68-year-old woman, with the plasmid
      pSV3 neo. The plasmid included coding sequences and promotors for the large and
      small T antigens of the SV40 virus as well as resistance to the antibiotics
      neomycin and G418. A single antibiotic-resistant colony was located and cloned.
      Large tumor antigen production in the clonal cell line was confirmed by indirect
      immunofluorescence study. Treatment with 1,25-dihydroxy-vitamin D3 increased
      steady-state concentrations of protein and mRNA for osteocalcin and for alkaline
      phosphatase. Northern blot analyses also demonstrated the presence of mRNAs for
      alpha(I)-procollagen, osteopontin 1a, transforming growth factor beta, and
      interleukin-1 beta. The plasma membrane calcium pump and osteonectin were
      identified by immunocytochemical analysis. These cells produced a matrix that
      mineralized when beta-glycerophosphate was added to their cultures. As assessed
      by functional receptor assays, both estrogen and androgen receptors were present
      and functional, although at low concentrations. Treatment with parathyroid
      hormone did not stimulate adenylate cyclase activity. Thus, these cells are a
      well-differentiated, steroid-responsive clonal cell line that closely
      approximates the phenotype of the mature osteoblast. They should serve as an
      excellent model for the study of osteoblast biology.

PMID- 1373930
TI  - 1,25-Dihydroxyvitamin D3 inhibits the passive transfer of cellular immunity by a
      myelin basic protein-specific T cell clone.
AB  - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and related analogs have been shown to
      exert immunoinhibitory effects on activated lymphocytes in vitro. However, the
      effects of the hormone on the mammalian immune response in vivo have not been
      well studied. To examine the possible immunoactions of 1,25-(OH)2D3 in vivo, we
      employed a murine model of experimental autoimmune encephalomyelitis (EAE). In
      this model, T helper lymphocyte clones developed from lines of lymphocytes
      reactive to myelin basic protein (MBP) confer MBP immunoreactivity and
      demyelinating central nervous system disease on syngeneic, naive recipients of
      the T cell clone. Similar to peripheral blood mononuclear cells incubated with
      mitogen, the T cell clone evaluated in this study expressed a high-affinity
      specific receptor for 1,25-(OH)2D3 (VDR; K(in) = 0.03 nM) upon exposure to MBP.
      The MBP-stimulated clone elicited a ninefold enhancement of the local delayed
      hypersensitivity (DTH) response when as few as 0.5 x 10(5) cells of the T cell
      clone were injected into the foot pad of recipient mice. The DTH response in the
      recipient was completely blocked when the clone was preincubated with greater
      than or equal to 10(-8) M 1,25-(OH)2D3 before transfer; the half-maximal
      inhibitory concentration of hormone (EC50) was 5 x 10(-9) M. These data indicate
      that exposure of antigen-reactive T helper lymphocytes to a VDR saturating
      concentration of 1,25-(OH)2D3 can dramatically lessen the expression of
      immunoreactivity in vivo.

PMID- 1373931
TI  - Relationship between collagen synthesis and expression of the osteoblast
      phenotype in MC3T3-E1 cells.
AB  - The MC3T3-E1 mouse calvaria-derived cell line has been used to study the role of
      collagen synthesis in osteoblast differentiation. MC3T3-E1 cells, like several
      previously characterized osteoblast culture systems, expressed osteoblast markers
      and formed a mineralized extracellular matrix only after exposure to ascorbic
      acid. Mineralization was stimulated further by beta-glycerol phosphate.
      Ultrastructural observations indicated that the extracellular matrix produced by
      ascorbic acid-treated cells was highly organized and contained well-banded
      collagen fibrils. Expression of osteoblast markers followed a clear temporal
      sequence. The earliest effects of ascorbic acid were to stimulate type I
      procollagen mRNA and collagen synthesis (24 h after ascorbate addition), followed
      by induction of alkaline phosphatase (48-72 h) and osteocalcin (96-144 h) mRNAs.
      Procollagen mRNA, which was expressed constitutively in the absence of ascorbate,
      increased only twofold after vitamin C addition. In contrast, alkaline
      phosphatase and osteocalcin mRNAs were undetectable in untreated cultures.
      Actions of ascorbic acid on osteoblast marker gene expression are mediated by
      increases in collagen synthesis and/or accumulation because (1) parallel dose
      response relationships were obtained for ascorbic acid stimulation of collagen
      accumulation and alkaline phosphatase activity, and (2) the specific collagen
      synthesis inhibitors, 3,4-dehydroproline and cis-4-hydroxyproline, reversibly
      blocked ascorbic acid-dependent collagen synthesis and osteoblast marker gene
      expression.

PMID- 1373932
TI  - Mammalian nitric oxide synthases.

PMID- 1373933
TI  - Cigarette smoking, obesity, and benign prostatic hypertrophy: a prospective
      population-based study.
AB  - The authors examined the relation of smoking and obesity to surgically treated
      benign prostatic hypertrophy in a prospective study of white men aged 40-79 years
      who were first examined in 1972-1974 and were followed for an average of 12
      years. After exclusion of those whose surgery preceded assessment of smoking and
      obesity and those who had prostate cancer, there were 165 cases of benign
      prostatic hypertrophy among 929 men. Age-adjusted relative risk of benign
      prostatic hypertrophy in current or previous smokers compared with nonsmokers was
      1.1 (95% confidence interval 0.8-1.6). Age-adjusted relative risk of benign
      prostatic hypertrophy in the most obese tertile (body mass index (kg/m2) greater
      than 26.75) compared with the remainder showed a relative risk of 0.9 (95%
      confidence interval 0.6-1.4). Multivariate analysis also failed to show a
      relation between cigarette smoking or obesity and the development of surgically
      treated benign prostatic hypertrophy.

PMID- 1373934
TI  - Identification of a nonframeshift 84-bp deletion in exon 13 of the cystic
      fibrosis gene.
AB  - Cystic fibrosis (CF) is the most frequent autosomal recessive inherited disorder
      in Caucasian populations. The disease is caused by mutations in the CF
      transmembrane conductance regulator (CFTR) gene. We have identified an 84-bp
      deletion in exon 13 of the CFTR gene, detected by DNA amplification and direct
      sequencing of 500 bp of the 5' end of exon 13. The deletion was in the maternal
      allele of a CF patient bearing the delta F508 deletion in the father's allele.
      The same 84-bp deletion could also be detected in the patient's mother. The
      deletion spanned from a four-A cluster in positions 1949-1952 to another four-A
      cluster in positions 2032-2035, including 84 bp which correspond to codons 607
      634 (1949del84). The reported mutation would result in the loss of 28 amino acid
      residues of the R domain of the CFTR protein.

PMID- 1373935
TI  - A frameshift mutation (2869insG) in the second transmembrane domain of the CFTR
      gene: identification, regional distribution, and clinical presentation.

PMID- 1373936
TI  - Stability and sorption of FK 506 in 5% dextrose injection and 0.9% sodium
      chloride injection in glass, polyvinyl chloride, and polyolefin containers.
AB  - The effects of the diluent, the storage container, light, and infusion through
      various types of tubing on the stability and sorption of FK 506 were studied.
      Solutions of FK 506 in 0.9% sodium chloride injection or 5% dextrose injection
      were stored at room temperature (24 +/- 2 degrees C) in glass i.v. bottles,
      polyvinyl chloride (PVC) minibags, and polyolefin containers. FK 506 solution in
      0.9% sodium chloride injection was stored in plastic syringes at room temperature
      and either exposed to normal room light or stored in the dark. FK 506 solution in
      5% dextrose injection was placed in plastic syringes and infused through PVC
      anesthesia extension tubing, PVC i.v. administration set tubing, and fat emulsion
      tubing over a two-hour period. The infused samples and samples collected from the
      containers and syringes at intervals up to 48 hours were analyzed for FK 506
      concentration by high-performance liquid chromatography. FK 506 concentrations
      remained greater than 90% of initial concentration for admixtures in 5% dextrose
      injection stored in glass bottles for 48 hours and for admixtures in 5% dextrose
      injection or 0.9% sodium chloride injection stored in polyolefin containers for
      48 hours. No change in concentration was measured for admixtures in 0.9% sodium
      chloride injection stored in plastic syringes, and exposure to light did not
      affect the stability of FK 506 solution. No substantial change in concentration
      occurred in FK 506 solution in 5% dextrose injection infused through PVC
      anesthesia extension tubing, PVC i.v. administration set tubing, or fat emulsion
      tubing. FK 506 admixtures prepared with 5% dextrose injection or 0.9% sodium
      chloride injection should be stored in polyolefin containers. If polyolefin
      containers are not available, solutions should be prepared with 5% dextrose
      injection and stored in glass bottles.

PMID- 1373937
TI  - Comparison of intraosseous and intravenous delivery of hypertonic saline/dextran
      in anesthetized, euvolemic pigs.
AB  - STUDY OBJECTIVES: With renewed interest in intraosseous (IO) infusion, the
      present study examined if sternal IO infusion provided vascular entry of 7.5%
      NaCl/6% dextran-70 (HSD) as efficiently as IV infusion. DESIGN, SETTING, TYPE OF
      PARTICIPANTS, INTERVENTIONS: Twelve anesthetized pigs were catheterized for
      measurement of cardiovascular parameters. Six pigs were given a 4-mL/kg IO
      infusion of HSD under pressure over two to six minutes; each pig was paired with
      another that had been given HSD IV over the same time course. Rapid arterial
      blood sampling was used to evaluate vascular entry of NaCl and dextran with
      monitoring continued for two hours after infusion. MEASUREMENTS AND MAIN RESULTS:
      Complete vascular entry of infused sodium and dextran was generally complete
      within one minute after infusion in all experiments. Increases in mean arterial
      pressure, cardiac output, and other cardiovascular parameters were
      indistinguishable between IO and IV infusions. Plasma volume expansion was about
      20% above baseline in both groups of pigs. Histologic examination showed minimum
      pathology to the sternum and no significant pulmonary complications. CONCLUSION:
      1O vascular delivery of HSD is a viable alternative in emergency scenarios in
      which vascular access is compromised.

PMID- 1373938
TI  - Sequential silastic and expandable metal stenting for tracheobronchial
      strictures.
AB  - The risks and limitations of surgical resection and reconstruction for
      tracheobronchial strictures demand consideration of other therapeutic options
      that can alleviate the distressing symptoms of tracheobronchial obstruction. One
      alternative is to stent the obstructive lesion until surgical advances allow
      primary reconstruction or replacement of the critically diseased airway or until
      an ideal endoprosthesis is found. The latter requires uniformity in the
      distribution of expansile force, conformability and stability within the
      tracheobronchial tree, and ease of placement. Here we report our experience with
      the placement of expandable metal stents (Wall-stent) used in conjunction with
      our Silastic (Dow Corning) endobronchial stents in 5 patients with recurrent
      tracheal or bronchial strictures. The major site of obstruction was the trachea
      in 1 patient and a main bronchus or both bronchi in 4 patients. Three patients
      had a benign bronchial stricture (anastomotic stricture in 2, idiopathic
      polychondritis in 1), and 2 patients had an obstructive airway neoplasm.
      Placement of the stents was performed under rigid bronchoscopic guidance. We had
      no complications from our technique of stenting. There has been no evidence of
      restenosis or occlusion within the stented segment of airway. The complementary
      use of expandable metal and Silastic endobronchial stents provided symptomatic
      and functional improvement in our patients during follow-up ranging from 5 to 24
      months.

PMID- 1373939
TI  - Relation between drug resistance and antigenicity among norakin-resistant mutants
      of influenza A (fowl plague) virus.
AB  - Norakin-resistant (NR) mutants of fowl plague virus (A/FPV/Weybridge, H7N7) have
      1 to 2 (in one instance 3) amino acid substitutions in different positions of the
      heavy (HA 1) and/or light (HA 2) subunits of the haemagglutinin (HA) molecule.
      Investigation of NR mutants using the haemagglutination inhibition test with
      monoclonal antibodies (MAb) to the HA of A/seal/Massachusetts/80 (H7N7) virus
      revealed that one of the mutants (NR 1) differs antigenically from the wild-type
      fowl plague virus: its haemagglutination was not inhibited by MAb 55/2 and 58/6.
      By contrast, MAb-resistant (escape) mutants, selected from the wild-type fowl
      plague virus under pressure from MAb 55/2 or 58/6, showed reduced drug
      sensitivity. These findings suggest a possibility of correlation between
      alteration of influenza virus antigenicity and change of its sensitivity to drugs
      whose target is the haemagglutinin. This potential effect should be taken into
      account when antiviral substances directed to surface influenza virus antigens
      are being developed for use as antiviral drugs.

PMID- 1373940
TI  - Use of Brefeldin A to localize block in intracellular transport of vesicular
      stomatitis virus G protein on interferon-treated cells.
AB  - Brefeldin A (BFA) induced a rapid redistribution of vesicular stomatitis virus G
      protein (VSV-G) to the endoplasmatic reticulum (ER) in interferon (IFN)
      pretreated cells. This result is consistent with accumulation of VSV-G in the
      trans-Golgi (GC) complex in cells pretreated with IFN and implies that IFN does
      not interfere with the ability of BFA to induce redistribution of proteins from
      GC to ER.

PMID- 1373941
TI  - Evolution of the cellular response in P2-induced experimental allergic neuritis.
AB  - We examined the development of the inflammatory cellular response and
      demyelination in P2 protein-induced experimental allergic neuritis (EAN).
      Collections of inflammatory cells were first identified in nerve roots 14 days
      after immunization. Ia+ cells predominated in the evolving lesions and T-helper
      cells were the dominant T-cell type with T-suppressor/cytotoxic cells appearing
      later in the course of the disease. Vesiculation, the earliest change seen in the
      myelin sheath, appeared before the wave of cellular infiltration. These results
      indicate that myelin injury precedes inflammation in P2 protein-induced EAN, and
      provide further evidence that this disorder is indistinguishable from EAN induced
      with whole peripheral nerve myelin.

PMID- 1373942
TI  - Semidry electrophoretic transfer of RNA to membranes.
AB  - We describe a method using a semi-dry gel electro-blotter to transfer RNA from
      standard agarose-formaldehyde denaturing gels in less than 30 min. The method
      requires equilibrating the gel in a low ionic strength buffer. The transfer is
      done under high-current and low-voltage conditions. This method maintains the
      overall sharpness of the bands on the final autoradiogram while shortening the
      time required for Northern transfer by approximately 12 hours.

PMID- 1373943
TI  - Reproduction of autoradiograms and gels with contact negatives and prints.

PMID- 1373944
TI  - Simple, rapid, reversible staining of nucleic acid immobilized on blots.

PMID- 1373945
TI  - Inhibitory effect of purines in meiotic maturation of denuded mouse oocytes.
AB  - The potential action of purines, such as hypoxanthine and adenosine, in meiotic
      arrest was examined using denuded mouse oocytes. The spontaneous meiotic
      maturation of denuded oocytes was significantly inhibited by hypoxanthine and/or
      adenosine in a dose-dependent manner. Germinal vesicle breakdown (GVBD) was
      inhibited even at a low concentration (1 nM) of hypoxanthine, when hypoxanthine
      was microinjected into the cytoplasm of denuded oocytes. This inhibitory action
      was potentiated by co-injection with allopurinol, a metabolic blocker of
      hypoxanthine that can block a metabolic pathway to uric acid. By contrast, a
      microinjection of adenosine was no longer effective in inhibiting GVBD.
      Inhibitory action of purines in meiotic maturation was correlated with sustaining
      intracellular cAMP levels. GVBD was resumed by econazole, one of the
      nitroimidazole derivatives which act as inhibitors of catalytic subunit of
      adenylate cyclase. This compound was effective in counteracting the effect of
      adenosine, but not the action of 3-isobutyl-1-methylxanthine (IBMX) on GVBD,
      indicating that adenosine is probably exerted at the level of oocyte plasmalemma.
      These data suggest that the inhibitory action of hypoxanthine and adenosine in
      oocyte meiotic maturation may be involved in the regulation of cAMP metabolism in
      a differential manner.

PMID- 1373947
TI  - Evaluation of medical students' hospital training: interest of students' essays.
AB  - To evaluate the impact of teaching during hospital training in an adult cancer
      ward, 107 consecutive students were asked to freely select the chart of a patient
      representative of their course and to write comments on it, at the end of their
      course. Students selected charts of young patients rather than older ones (P less
      than 0.0001). Most of the patients had a poor prognosis (69%). Students
      frequently emphasized psychosocial aspects of cancer and patient's information
      (patient-student relationship: 50%; diagnosis acceptance: 36%; information: 19%),
      but rarely considered post-treatment sequelae of cured patients (4%), palliative
      care (9%), and truth (10%). The selection of a large majority of poor prognosis
      patients led us to invite them to attend consultations to meet patients who are
      cured or in fair condition. Other topics must be emphasized (palliative care,
      truth, and post-treatment morbidity). Finally, such an evaluation provides good
      information on the course of the students and is easily performed and analysed.

PMID- 1373946
TI  - Ontogeny of reticulum cells in the rat intestine and their possible role in the
      development of the lymphoid microenvironment.
AB  - Ontogeny of reticulum cells (RC) in the rat intestine in relation to the
      development of the gut-associated lymphoid tissue (GALT) was studied using a
      panel of monoclonal antibodies (mab) directed against RC in peripheral lymphoid
      organs, ED10-ED15. The mab ED10 specific for RC in the spleen T cell area,
      recognized an epitope on gut RC, which cells seem to be involved in the influx
      and accumulation of lymphocytes in the lamina propria and in Peyer's patches (PP)
      and proximal colonic lymphoid tissue (PCLT). The mab ED11 which recognizes RC in
      the T cell area and B cell follicles of spleen, stained follicular dendritic
      cells (FEC) in the B cell area of the mesenteric lymph node (MLN), PP and PCLT.
      The ED11 expression occurs earlier and reveals stronger staining in MLN as
      compared to those in PP and PCLT, suggesting the prominent role of MLN in the
      generation and proliferation of B cells in the gut mucosal immune system. The mab
      ED13 specific for RC in the B cell area of the lymph nodes, stained the basement
      membrane of the epithelium overlying PP and PCLT, and high endothelial venules
      (HEV), suggesting that this might be involved in providing the microenvironment
      for the development and differentiation of follicle-associated epithelium, and
      facilitating lymphocyte traffic. The mab ED12 specific for RC in the paracortex
      of peripheral lymph nodes, gave a diffuse nonspecific staining in the gut,
      whereas mab ED14 and ED15 are markers for common connective tissue cells. We
      conclude that the gut RC are morphologically and phenotypically heterogenous.
      ED10+, ED11+, and ED13+ RC are probably involved in the development of the gut
      lymphoid microenvironment.

PMID- 1373948
TI  - Scarring alopecia in discoid lupus erythematosus.
AB  - The clinicopathological features of the scarring alopecia of discoid lupus
      erythematosus (DLE) were studied. Scarring alopecia was present in 34% of 89
      patients with DLE and was associated with a prolonged disease course. More than
      half these patients had scalp involvement at the onset of the disease. There was
      a significant reduction in size of sebaceous glands in affected scalp.
      Perifollicular lymphocytic inflammation was maximal around the mid-follicle at
      the level of the sebaceous gland, which seems to be an important functional level
      in the follicle. There are changes in the expression of the matrix molecules, the
      proteoglycans, in the connective tissue sheath and the keratin intermediate
      filaments in the outer root sheath cells at this level in normal scalp and in
      diseased scalp. Loss of a population of mid-follicular stem cells may be
      important in the pathogenesis of scarring alopecia in DLE.

PMID- 1373949
TI  - Epidermal cytokeratin and immunocyte responses during treatment of psoriasis with
      calcipotriol and betamethasone valerate.
AB  - Changes in epidermal immunocytes and cytokeratins were investigated during
      treatment of psoriasis with calcipotriol and betamethasone valerate. Skin
      biopsies were obtained from 10 subjects on each treatment from lesional and non
      lesional skin at baseline, and from treated lesions after 4 weeks. In each
      subject, changes in expression of cytokeratins K5, K10 and K16, and changes in
      epidermal immunocyte counts were assessed. Responses were compared with a
      separate histological parameter of improvement, epidermal thickness. Both
      treatments produced a marked normalization of cytokeratins. The reduction of K16
      expression was similar on each treatment and correlated significantly with
      reduction in epidermal thickness. Expression of both K5 and K10 improved less
      than thickness with betamethasone valerate but more than thickness with
      calcipotriol, although these differences did not reach statistical significance.
      With calcipotriol there was an increase in K5 and K10 responses with increasing
      response of epidermal thickness, which was not seen with betamethasone valerate.
      T6+ cells, HLA-DR+ dendritic cells and T lymphocytes were all reduced by
      betamethasone valerate. There was a remarkable similarity in the level of
      normalization between cell types and also between cellular response and reduction
      in thickness. Calcipotriol produced a similar consistent reduction in cell
      numbers and in thickness, with the exception of T6+ cells which increased in some
      subjects during treatment. Only in subjects in whom thickness had virtually
      returned to normal was there a marked decrease in T6+ cells.

PMID- 1373950
TI  - CD8+ cutaneous anaplastic large-cell lymphoma: report of two cases with
      immunophenotyping, T-cell-receptor gene rearrangement and electron microscopic
      studies.
AB  - Two cases are reported of cutaneous anaplastic large-cell lymphoma with the
      suppressor/cytotoxic (CD8) phenotype. In both cases there was a solitary skin
      tumour in which there was a dense infiltrate with large irregularly shaped cells
      which on immunophenotyping expressed CD8. DNA hybridization analysis showed
      rearrangements of the T-cell-receptor gene in both cases.

PMID- 1373951
TI  - Heparin enhances angiogenesis by a systemic mode of action.
AB  - A systemically-administered standard sodium heparin, but not an oligosaccharide
      fraction derived from the heparin, significantly potentiated angiogenesis induced
      by saline in normal rats, as assessed by the quantitative mesenteric window
      angiogenesis assay. This is the first unambiguous evidence that any single
      specific mast-cell product can potentiate angiogenesis in normally vascularized
      mammalian tissue. Whether systemic treatment with a heparin-like substance may be
      useful for stimulating neoangiogenic formation of collaterals in situations of
      relative microvascular insufficiency, such as coronary collaterals in patients
      suffering from ischaemic heart disease, is briefly discussed.

PMID- 1373952
TI  - Changes in permissiveness for the expression of microinjected DNA during the
      first cleavages of mouse embryos.
AB  - LacZ DNA and LacZ RNA were microinjected during the first cleavages of embryos.
      LacZ DNA was not expressed before 18-19 h post insemination (hpi) but LacZ RNA
      was translated. Before 22 hpi LacZ DNA was expressed in the pronuclei of the one
      cell embryos and the polypeptides of the minor, but not the major activation
      period of the genome were synthesized. This suggests a negative control of
      transcription before 18-19 hpi and demonstrates that its resumption is
      independent of the first cleavage and of the major activation of the genome. At
      the time of the minor activation the eggs contain the trans-acting elements to
      express a variety of genes that they do not express. It may indicate that, the
      minor and the major activation of the genome are differently controlled.

PMID- 1373953
TI  - Expression of activins and TGF beta 1 and beta 2 RNAs in early postimplantation
      mouse embryos and uterine decidua.
AB  - The expression of the mesoderm inducing factors, activins and TGF beta s, was
      characterized in 5 1/2-9 1/2 day mouse embryos and implantation sites by in situ
      hybridization. Activin beta A RNA was not detected within the embryo, but is
      expressed in nearby decidual cells from 5 to 7 days. Thus activin A could play a
      role within the embyro during gastrulation. Activin beta A is also expressed in
      more mesometrially located decidual cells from 6 to 9 1/2 days. Activin beta B
      and inhibin alpha RNAs were not detected, while a control tissue was highly
      positive. TGF beta 1 is expressed in the secondary decidual zone and in
      developing endothelial cells in the decidua and embryo. TGF beta 2 is expressed
      in the mesometrial decidua at 6 1/2 days and in the midline of the cranial neural
      plate.

PMID- 1373954
TI  - In vivo transient rise in plasma free fatty acids alters the functional
      properties of alpha-fetoprotein.
AB  - Previous in vitro studies have shown that unsaturated fatty acids (UFA) induce
      conformational changes in rodent and human alpha-fetoprotein (AFP). To determine
      whether such changes in the binding and immunological properties of rat AFP also
      occur in vivo, plasma free fatty acid (FFA) concentrations were increased in
      young male rats (15, 21 and 28 days old) by acute i.v. injection of heparin (200
      IU/kg). Plasma estrogens (estrone and estradiol) did not change after injection
      of heparin. There was a large increase in plasma FFA 10-20 min post-heparin
      injection, with a return to normal 60 min later. This transient rise in FFA
      plasma was associated with a 50% drop (P less than 0.001) in the binding of
      estradiol to rat AFP of 15-, 21- and 28-day-old rats by reducing the number of
      binding sites (P less than 0.001), leaving the affinity constant (Ka) unchanged.
      FFA extracts from post-heparin plasma induced similar changes in estradiol
      binding to purified rat AFP. The rise in plasma FFA induced a loss of AFP
      immunoreactivity, in 21- (P less than 0.001) and 28-day-old rats (P less than
      0.001), but not in 15-day-old rats. This age-dependent response correlated with
      the FFA/AFP molar ratio (38 in 15-day-old rats, 388 in 21-day-old rats, and 5600
      in 28-day-old rats). These results indicate that an in vivo rise in FFA induces
      rapid and reversible conformational changes in AFP which may modulate the
      endocrine and immune function of this oncofetal protein.

PMID- 1373955
TI  - Fetal rat cerebellar fragment transplantation into adult rat forebrain lesion
      cavities.
AB  - Fragments of fetal rat cerebellar tissue were grafted into forebrain cortical
      lesion cavities of adult rats. After a survival ranging from 12-151 days, no
      graft was found to fill the cavity completely. Large neurons, occasionally
      grouped into nests, were identifiable from the 22nd day. Myelinated graft fibers,
      first seen at 32 days, failed to enter host brain. Although grafts demonstrated
      elements resembling cerebellar tissue, overall organization did not resemble that
      of the cerebellum.

PMID- 1373956
TI  - [The value of plasma proteins in the postoperative follow-up of surgery on
      gastrointestinal tumors: the effect of nutritional support].
AB  - During the postoperative period after radical surgery on oesophagogastric (EG) or
      colorectal (CR) tumours, we have studied prospectively the influence that factors
      like protein-calorie malnutrition (PCM), the degree of stress and the
      characteristics of total parenteral nutrition (TPN) may have on the postoperative
      levels of certain plasma proteins (PP), especially those of rapid turnover, like
      acute phase reactant proteins (APRP). 44 patients (23 EG and 21 CR) were assigned
      randomly to receive one of two regimes of isonitrogenated TPN (0.23 g/Kg
      weight/day) during the first six postoperative days. The only difference between
      the two regimes was the relationship Kcal/g N2 (Group I Kcal/g N2 = 100, Group II
      Kcal/g N2 = 150). The percentage of preoperative PCM was 45%. Apart from albumin
      (A) and transferrin (T), all the PP recovered their preoperative values on the
      6th postoperative day, with very significant increases of haptoglobin (HP) and
      alpha-1-antitrypsin (AAT) (p less than 0.01). Previous MN, the types of surgery
      or the ratio Kcal/g N2 hardly modified this response. The cumulative nitrogen
      balance (CNB) was significantly more positive in patients with previous PCM (p
      less than 0.05), and in those who underwent EG surgery (p less than 0.05) and in
      those of GI (p less than 0.02). The rate of postoperative septic complications
      (PSC) was higher in EG and MN patients (p less than 0.01) and was manifested by
      significantly lower levels of fibronectin (F) and prealbumin (PA) (p less than
      0.01). Preoperative values of A, PA and total proteins (TP) have been shown to
      have predictive value in PSC.

PMID- 1373958
TI  - Prolonged cold storage abolishes endothelium-dependent relaxing responses to
      A23187 and substance P in porcine coronary arteries.
AB  - In the presence of potassium (K+), A23187 and substance P elicited endothelium
      dependent relaxations of porcine coronary arteries. Isoproterenol or hypoxia
      elicited endothelium-independent relaxations. Rubbing the artery potentiated the
      contractile response to a low K+ concentration (15.4 mM). After intact arteries
      had been stored at 5 degrees C for 3 days, K(+)-induced maximal tension was not
      affected, but contractile responses to 15 mM K+ were potentiated with a decrease
      in ED50, suggesting that cold storage produces a supersensitivity to K+.
      Endothelium-dependent relaxations were abolished after 3 days of cold storage,
      while endothelium-independent relaxations were not inhibited. Cold storage of
      arteries with l-arginine (1 mM) for 3 days did not alter the relaxation responses
      to substance P and A23187, indicating that l-arginine does not prevent the loss
      of endothelium-dependent relaxation. Cold storage for 5 days inhibited the
      maximal tension to K+ and abolished the supersensitivity. Scanning electron
      micrographs showed that endothelial cells can be damaged by prolonged cold
      storage. The changes in tension response of the artery were correlated with the
      time course of endothelial cell loss resulting from cold storage.

PMID- 1373959
TI  - Capillary occlusion and secondary angiogenesis in a patient with Raynaud's
      phenomenon.

PMID- 1373957
TI  - Multiparameter analyses of normal and malignant human plasma cells: CD38++,
      CD56+, CD54+, cIg+ is the common phenotype of myeloma cells.
AB  - Plasma cells obtained from bone marrow samples of 45 patients with MM, eight
      patients with MGUS, eight patients with Waldenstrom's macroglobulinaemia (WM),
      one patient with immunocytoma, and 12 controls were characterized by
      immunophenotyping, estimation of DNA content, and labeling index, as well as by
      morphological analysis. Plasma cells from 37/45 myeloma and 5/8 MGUS patients
      expressed CD38 and CD56 (N-CAM) on their surface but were negative for other NK
      cell-associated antigens such as CD16 (Fc gamma RIII) or CD2. All tumor cells of
      less-differentiated cell type (WM, immunocytoma) and normal polyclonal plasma
      cells were negative for CD56. CD56-specific mRNA was demonstrated in myeloma
      cells by northern blot analysis. Another adhesion molecule, ICAM-1 (CD54), was
      found on plasma cells from all patients and controls examined. Coexpression of
      CD19 (1/45), CD20 (9/45), or CD33 (3/45) was rare and CD10 with CD14 was
      expressed by a small tumor cell subpopulation of only one myeloma patient. The
      individual pattern of surface marker expression was not associated with a special
      type myeloma protein isotype, stage or status of disease, LI or histological
      classification; however, a correlation between CD56 expression or histological
      classification and DNA content of the tumor cells was found.

PMID- 1373960
TI  - Mapping epitope specificities of monoclonal antibodies to thyroid peroxidase
      using recombinant antigen preparations.
AB  - Five separate monoclonal antibodies (MoAbs) to human thyroid peroxidase (hTPO)
      were raised by immunising Balb/c mice with hTPO purified from detergent
      solubilised thyroid microsomes by high performance liquid chromatography (HPLC).
      The epitope specificities of these MoAbs were determined by assessing their
      ability to bind to purified recombinant fusion protein fragments of human TPO
      (TPO(r)) generated in E. coli. A total of seven small overlapping fragments
      (averaging 104 amino acid residues) of hTPO, encompassing over 90% of the
      extracellular region of the molecule, were generated as glutathione S-transferase
      (GST) fusion proteins. The sequential epitopes on TPO(r) recognised by these
      MoAbs were analysed by both immunoblotting and enzyme linked immunosorbent assay
      (ELISA). Two different MoAbs (A4 and A5) recognised sequential epitopes within
      the TPO(r) preparation termed R1a + b (residues 1-160) and more specifically, in
      the case of MoAb A4, within the subfragment R1b (residues 70-160). The inability
      of the other MoAbs (A1-A3) to recognise recombinant fragments, suggests they
      either recognise conformational determinants on the TPO molecule or epitopes that
      are present on the small regions of the TPO molecule which have not been
      expressed as recombinant proteins.

PMID- 1373961
TI  - Autoimmune thyroiditis and targeted anti-T cell immunotherapy in man.

PMID- 1373962
TI  - The third Euromyasthenia Conference; meeting report and update on myasthenia
      research.

PMID- 1373963
TI  - Prenatal biochemical screening for Down's syndrome and neural tube defects.
AB  - Antenatal serum screening for Down's syndrome is now becoming established in many
      centers throughout the world. The screening method is based on the measurement of
      alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin between
      15 and 22 weeks of pregnancy. These measurements, used in conjunction with a
      woman's age, provide risk estimates of having a pregnancy with Down's syndrome
      for every woman screened. By identifying the 5% of women with highest risk and
      offering them an amniocentesis, about 60% of Down's syndrome pregnancies can be
      identified. If an ultrasound scan examination is used routinely to estimate
      gestational age, the detection rate can be increased by 5% to 10%. Recent
      information on the distribution of the three serum markers in twin pregnancies
      and pregnancies with insulin-dependent diabetes mellitus now means that screening
      can be carried out in such pregnancies. Various other serum markers of Down's
      syndrome have been reported, but at present they do not have a place in routine
      antenatal screening for Down's syndrome. The role of amniotic fluid
      acetylcholinesterase measurement, alone and in combination with amniotic fluid
      alpha-fetoprotein measurement, in the antenatal diagnosis of open neural tube
      defects has recently been clarified. The best policy is to perform an amniotic
      fluid alpha-fetoprotein measurement as the primary test and an
      acetylcholinesterase determination for those women who have an amniotic fluid
      alpha-fetoprotein measurement of two times the normal median or greater. The
      acetylcholinesterase can be measured either by the standard method (gel
      electrophoresis) or by a new quantitative monoclonal antibody method.

PMID- 1373964
TI  - A retrospective study on the patterns of sequential fluctuation of serum alpha
      fetoprotein level during progression from liver cirrhosis to hepatocellular
      carcinoma.
AB  - The patterns of sequential fluctuation of serum alpha-fetoprotein levels were
      analysed in 218 patients with liver cirrhosis in whom the serum alpha-fetoprotein
      levels were regularly and serially measured for more than 1 year. In the group of
      patients with persistently abnormal high values (greater than 50 ng/mL) over a
      follow-up period of more than 1 year, the incidence of the subsequent development
      of hepatocellular carcinoma was statistically and significantly higher (44%)
      compared to the other groups which showed normal (less than 20 ng/mL) or low
      abnormal levels (21-50 ng/mL) (16%), and transient abnormal high levels (greater
      than 50 ng/mL for a period of less than 1 year, mostly within 5 months) or
      fluctuated repeatedly between normal and transient abnormal high levels (23%).
      Hepatocellular carcinoma developed in 48 patients more than 2 years after the
      diagnosis of liver cirrhosis, and the fluctuating patterns of serum alpha
      fetoprotein levels were analysed in these patients. The serum alpha-fetoprotein
      levels in 10 of these 48 patients stayed below 50 ng/mL until about 2.0-10.0
      months before the detection of hepatocellular carcinoma and then increased
      steadily until the time of hepatocellular carcinoma detection. In these 10
      patients, the monthly increasing ratios were approximately 1.6-4.8 times the
      previous values.

PMID- 1373966
TI  - [The results of the chemoembolization of advanced hepatocellular carcinomas. The
      effect on the survival times, morphological findings and tumor markers].
AB  - Chemoembolization is a well-recognized therapeutic procedure in the treatment of
      stage I and stage II hepatocellular carcinoma (HCC). Until now it is rarely used
      in the treatment of stage III HCC. In a prospective study we analysed the
      efficacy and the side effects of chemoembolization in 16 patients with stage III
      HCC. Chemoembolization was performed with an emulsion of lipiodol, 4-epirubicin
      and cisplatinum. All patients tolerated the treatment without remarkable
      complications. With 9 months the median survival rate was considerable higher
      than the survival rate of untreated patients and of patients treated with
      systemic chemotherapy or with local perfusion.

PMID- 1373965
TI  - The effect of chilli ingestion on gastrointestinal mucosal proliferation and
      azoxymethane-induced cancer in the rat.
AB  - Of the three main races of Singapore, Malays and Indians are less susceptible to
      gastric and colorectal carcinoma and peptic ulcer when compared with Chinese.
      Racial differences in dietary habits include a smaller amount of chilli consumed
      by the Chinese when compared with the other two races. Chilli may be expected to
      accelerate gastrointestinal transit and hence to inhibit colonic carcinogenesis,
      while its active ingredient capsaicin protects against experimental gastric
      mucosal injury. The effect of chilli consumption was studied in relation to: (i)
      gastrointestinal crypt cell production rate and nucleic acid content as indices
      of mucosal proliferation, which is related to the risk of development of
      gastrointestinal cancer and peptic ulcer; and (ii) azoxymethane-induced
      intestinal cancer. Sprague-Dawley rats (n = 102) received either standard
      powdered chow or chow supplemented with 100 or 200 mg of chilli powder daily for
      1, 18 or 24 weeks. Gastric, small-bowel and colonic crypt cell production rates
      were studied at all three time periods, while mucosal DNA, RNA and protein
      contents were measured at 1 and 24 weeks. While crypt cell production rates were
      unaffected by chilli ingestion, mucosal contents of nucleic acid and protein were
      mostly increased in chilli-fed animals compared to controls, especially in the
      colon at 24 weeks. A further 99 rats received subcutaneous injections of either
      azoxymethane 15 mg/kg/week x 6 or sterile water and were randomized to the same
      three dietary groups for 26 weeks. The number, size and location of benign and
      malignant duodenal and colonic tumours were unaffected by chilli intake.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1373968
TI  - Hematopoietic growth factors released by marrow stromal cells from patients with
      aplastic anemia.
AB  - We studied the production of granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-6 (IL
      6) by stromal cells from 33 patients with aplastic anemia (AA). Complete,
      confluent stromal layers were produced by 29 of the 33 samples using the long
      term bone marrow culture (LTBMC) system. The concentration of G-CSF, GM-CSF, and
      IL-6 in culture media with or without interleukin-1 (IL-1) stimulation was
      determined by an enzyme-linked immunoadsorbent assay (ELISA). The spontaneous
      production of G-CSF, GM-CSF, and IL-6 did not differ significantly between normal
      controls and the patients with AA. The ability of stromal cells to release the
      three hematopoietic growth factors in response to IL-1 was either normal or
      elevated in all but one patient. We also studied the change in production of G
      CSF, GM-CSF, and IL-6 by stromal cells before and after antilymphocyte globulin
      (ALG) therapy in 16 patients with AA. There was no correlation between the change
      in production of these cytokines and the response to ALG. In contrast to previous
      studies that showed a defect in the production of hematopoietic growth factors by
      stromal cells from patients with AA, the results indicated a normal or elevated
      production of G-CSF, GM-CSF, and IL-6 by marrow stromal cells in patients with
      AA.

PMID- 1373967
TI  - In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin
      against human pre-B cell acute lymphoblastic leukemia in mice with severe
      combined immunodeficiency.
AB  - A highly aggressive subclone of the human CALLA+C mu+ pre-B acute lymphoblastic
      leukemia (ALL) cell line NALM-6 (designated NALM-6-UM1) caused disseminated and
      fatal leukemia in CB.17 mice with severe combined immunodeficiency (SCID). An
      intravenous challenge with 1 x 10(6) (NALM-6-UM1 cells caused 15 of 27 (56%) SCID
      mice to become paraplegic at 31 +/- 2 days (median = 33 days) and 27 of 27 (100%)
      mice to die of disseminated leukemia at 38 +/- 1 days (median = 39 days). We used
      this SCID mouse model of aggressive human pre-B ALL to evaluate the in vivo
      antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP)
      immunotoxin. A 3-day treatment with nontoxic doses of B43-PAP markedly reduced
      the incidence of paraplegia and improved event-free survival (EFS) in SCID mice
      challenged with 1 x 10(6) NALM-6-UM1 pre-B ALL cells, as reflected by
      significantly higher cumulative proportions of mice free of paraplegia or alive
      at 1 to 7 months, as compared with phosphate-buffered saline (PBS) treated
      control mice. The Kaplan-Meier estimates and standard errors of the probability
      of developing paraplegia after inoculation of 1 x 10(6) NALM-6-UM1 cells was 64%
      +/- 10% for PBS-treated mice (median time to paraplegia = 37 days) (N = 27), 18%
      +/- 8% for mice treated with 15 micrograms B43-PAP (5 micrograms/mouse/d x 3
      days) (N = 23) and 5% +/- 5% for mice treated with 30 micrograms B43-PAP (10
      micrograms/mouse/d x 3 days) (N = 21). While 27 of 27 PBS-treated control SCID
      mice died of leukemia at 38 +/- 1 days (range = 24 to 54 days), only 16 of 44 B43
      PAP-treated mice developed leukemia at 74 +/- 12 days (range = 30 to 182 days),
      consistent with greater than or equal to 6 logs kill of clonogenic NALM-6-UM1
      cells in 64% of SCID mice. The Kaplan-Meier estimates and standard errors of the
      probability of long-term EFS after inoculation of 1 x 10(6) NALM-6-UM1 cells were
      65% +/- 10% for mice treated with 15 micrograms B43-PAP and 60% +/- 11% for mice
      treated with 30 micrograms B43-PAP with a median survival time of greater than 7
      months for both groups. In contrast, neither unconjugated B43 monoclonal antibody
      nor the anti-T-cell immunotoxin G17.2 (anti-CD4)-PAP decreased the incidence of
      paraplegia or improved EFS.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1373969
TI  - A comparison of therapeutic schedules for administering granulocyte colony
      stimulating factor to nonhuman primates after high-dose chemotherapy.
AB  - Granulocyte colony-stimulating factor (G-CSF) has been shown to be effective in
      clinical trials for reducing the period of neutropenia after chemotherapy. In
      this study, we compared the timing for initiating G-CSF administration after
      chemotherapy with the duration of neutropenia and hematopoietic regeneration.
      Nonhuman primates treated with high-dose chemotherapy (mechloroethamine, 1.5
      mg/kg, intravenously) and not administered G-CSF therapy experienced 8 days of
      neutropenia (absolute neutrophil count [ANC] less than 1,000/mm3) and had an ANC
      nadir of 124 +/- 64/mm3 at day 7. Monkeys receiving G-CSF (5 micrograms/kg/d,
      subcutaneously) began treatment on either days 1, 3, 5, or 7 after chemotherapy.
      Monkeys treated with G-CSF had an earlier ANC recovery and the number of days
      with an ANC less than 500/mm3 and ANC less than 1,000/mm3 was reduced by
      approximately 50% in all treatment strategies. All G-CSF-treated animals,
      irrespective of the time that G-CSF was initiated, reached an ANC of 10,000/mm3
      on day 13 +/- 1 day after chemotherapy. These results demonstrated that the
      duration of G-CSF therapy was almost twice as long for monkeys treated on day 1
      as it was for monkeys that received therapy beginning on day 7. A comparison of
      the results for all treated monkeys identified a distinct difference in the
      responses of monkeys treated on day 1 from that of animals treated with G-CSF at
      later times. G-CSF initiated 1 day after chemotherapy led to an earlier onset of
      neutropenia and a more rapid and augmented recovery of myeloid progenitor cells
      in the peripheral blood when compared with control and delayed therapy groups.
      This study demonstrates that neutropenia due to a single dose of mechloroethamine
      can be equally reduced with both early and delayed initiation of G-CSF. Further,
      initiating G-CSF therapy after 7 days required approximately 50% less days of
      therapy to reach an appropriate termination point. The applicability of these
      findings to other chemotherapy regimens and for repeated cycles is uncertain and
      needs to be further evaluated. This is a US government work. There are no
      restrictions on its use.

PMID- 1373970
TI  - Two types of murine CD34 mRNA generated by alternative splicing.
AB  - To characterize and clarify the function of CD34 antigen experimentally, we
      isolated two types of CD34 mRNA from a cDNA library of murine stromal cell line,
      PA-6 stimulated with lipopolysaccharide (LPS) and 12-o-tetra-decanoylphorbol 13
      acetate (TPA) using a human CD34 probe. In addition to the clone (open reading
      frame [ORF]:1149bp) reported by Brown et al, a novel clone (ORF:978 bp) was
      obtained. The difference between the two clones was in the cytoplasmic portion of
      CD34; the former has 73 amino acids, while the latter has 16. We investigated the
      genomic sequence of cytoplasmic portion and found conserved nucleotide sequences
      at the exon-intron junction (GT ... AG). Thus, it was concluded that alternative
      splicing gave two types of CD34 mRNA. A novel clone contains the longer cDNA,
      including a insert of 156 bp, but results in a shorter predicted coding sequence
      because of the introduction of an inframe stop codon. Northern blot analysis
      using a murine cDNA probe (HindIII fragment, 900 bp) showed that CD34 was highly
      expressed in the brain and testis, and moderately in the thymus, spleen, and bone
      marrow, but not in adult liver. However, day 12 to 14 fetal liver cells showed
      significant expression of CD34. Quantitative reverse transcription polymerase
      chain reaction showed that spleen, thymus, bone marrow, and testis RNA gave two
      bands of almost equal intensity, but in the brain a novel clone was expressed
      three times more than the other clone. Furthermore, Northern blot analysis using
      a probe (156 bp) specific for the spliced intracellular region confirmed the
      significant mRNA expression of a novel clone. Although the biologic significance
      of alternative splicing remains to be elucidated, it is suggested that a
      different carboxyterminal tail causes a change in signal transduction.

PMID- 1373971
TI  - Isolation and molecular characterization of the human CD34 gene.
AB  - The human CD34 surface antigen is selectively expressed on hematopoietic
      stem/progenitor cells, suggesting that it plays an essential role in early
      hematopoiesis. Using a 1.5-kb partial human CD34 cDNA sequence, RNA-polymerase
      chain reaction (PCR), and rapid amplification of cDNA ends (RACE) methods, we
      cloned and sequenced the full-length (2.65 kb) cDNA. The cDNA encodes a type I
      transmembrane protein with no obvious homology to other known proteins. The
      entire CD34 gene of 28 kb was cloned, and the coding sequences mapped to eight
      exons. Mapping of the 5' termini of mRNAs by 5'-RACE and RNAase protection
      analyses has indicated that the human CD34 gene uses multiple transcription
      initiation sites. Analysis of the upstream regulatory sequences revealed the
      absence of TATA and CAAT box sequences, and the presence of myb, myc, and ets
      like DNA binding motifs. We have identified significant homology between human
      and mouse CD34 genes in 5' and 3' untranslated regions, amino acid coding
      sequences, and 5' flanking sequences. This investigation of the CD34 gene should
      facilitate study of the function and regulation of this stem cell antigen.

PMID- 1373972
TI  - The Arg-Gly-Asp (RGD) recognition site of platelet glycoprotein IIb-IIIa on
      nonactivated platelets is accessible to high-affinity macromolecules.
AB  - We have characterized a murine IgG monoclonal antibody, OP-G2, specific for
      platelet glycoprotein (GP) IIb-IIIa (alpha IIb beta 3). OP-G2 Fab fragments
      inhibit fibrinogen-mediated platelet aggregation and competitively inhibit
      adenosine diphosphate-induced binding of 125I-fibrinogen to washed platelets. OP
      G2 binding to GPIIb-IIIa is specifically inhibited by RGD-containing peptides but
      not the fibrinogen gamma-chain carboxy-terminal peptide, and OP-G2 Fab fragments,
      like RGD-containing peptides, alter the conformation of GPIIb-IIIa resulting in
      the expression of a ligand-induced binding site (LIBS) recognized by PMI-1. OP-G2
      fails to bind to the recombinant Cam variant of GPIIb-IIIa (alpha III beta 3Cam)
      wherein an Asp119 to Tyr119 substitution in GPIIIa abrogates the ability to
      recognize RGD. These data indicate that OP-G2 recognizes an epitope at or in very
      close proximity to the RGD recognition site of GPIIb-IIIa and that, in every
      aspect tested, OP-G2 behaves like a macromolecular RGD ligand. Interestingly, two
      color flow cytometry shows that OP-G2 IgG can bind to nonactivated platelets.
      Quantitative binding assays indicate that nonactivated platelets bind
      approximately 50,000 125I-OP-G2 molecules/platelet. Furthermore, the affinity of
      OP-G2 for platelets activated with thrombin is roughly fivefold higher
      (nonactivated, kd = 24.8 nmol/L; activated, kd = 4.9 nmol/L). These results
      suggest that the RGD recognition site of GPIIb-IIIa is available to
      macromolecules that contain RGD even on nonactivated platelets, provided that the
      affinity of the ligand is adequate.

PMID- 1373973
TI  - Bone marrow-derived stromal cells prevent apoptotic cell death in B-lineage acute
      lymphoblastic leukemia.
AB  - Establishing requirements for the survival of human immature B cells in vitro has
      proved elusive. In this article, we report prolonged survival of B-lineage
      leukemic cells on 'feeder layers' of bone marrow (BM)-derived stromal cells in a
      serum-free environment. In 15 of 18 cases of B-lineage acute lymphoblastic
      leukemia (ALL), there was a greater than 50% decrease in the number of viable
      cells after 72 hours of culture in medium alone. Cell loss was preceded by
      molecular and cellular changes characteristic of programmed cell death, or
      apoptosis, and was not suppressed by adding interleukin-7 to the tissue culture
      medium. By contrast, the use of allogeneic BM stromal cells as feeder layers
      prevented apoptosis in 10 of 12 cases of ALL, leading to extended survival of the
      blast cells. This method was not successful when the allogeneic marrow cells were
      replaced with established cell lines. In six of eight cases in which the numbers
      of intact CD19+ lymphoblasts were counted by flow cytometry after 7 days of
      culture, the proportion of such cells recovered in the presence of BM stromal
      cells was 68.8% to 124.7% (median, 95.3%) of that originally seeded, as opposed
      to the 0.3% to 15.9% fraction (median, 0.7%) obtained in the absence of stromal
      cells. Survival requirements of the B-lineage lymphoblasts appeared to be
      heterogeneous, as cells from 3 of the 18 cases studied showed no signs of
      apoptosis in serum-free tissue culture medium that lacked BM stromal cells. The
      only cells not giving rise to viable cultures were from two hyperdiploid (greater
      than 50 chromosomes) cases with identical karyotypes. The serum-free assay
      described here can be used to compare the survival requirements of normal and
      leukemic B-cell progenitors as well as to identify the molecules involved in the
      interaction between BM stroma and immature B cells.

PMID- 1373975
TI  - Lack of apparent hematologic abnormalities in human patients with c-kit (stem
      cell factor receptor) gene mutations.

PMID- 1373974
TI  - Neural cell adhesion molecule-positive peripheral T-cell lymphoma: a rare variant
      with a propensity for unusual sites of involvement.
AB  - A distinct subset of patients with peripheral T-cell lymphoma (PTCL) is described
      which reacts with Leu-19 (CD56), an antibody that has been shown to identify the
      neural cell adhesion molecule (NCAM). These NCAM-positive PTCL patients (11 of a
      series of 46 PTCL; 24%) exhibited a striking predilection for unusual anatomic
      sites of involvement: central nervous system (36%), muscle (18%),
      gastrointestinal tract, and nasopharynx (27% each). Additional extranodal sites
      of involvement included the pituitary, thyroid, parathyroids, adrenals, and
      pancreas. The NCAM-positive subset also exhibited a characteristic phenotypic
      profile, with significantly lower expression of CD3 and CD5 compared with the
      NCAM-negative group. RNA transcripts consistent with the NCAM gene were detected
      in tissue samples from five Leu-19-positive cases using a reverse transcriptase
      polymerase chain reaction assay, supporting the idea that Leu-19 recognizes NCAM
      in these patient samples. This suggests that the expression of the NCAM plays a
      role in the behavior and localization of lymphomas. Because of the unique
      clinical and phenotypic characteristics of this group it may be designated as
      "NCAM-positive peripheral T-cell lymphoma."

PMID- 1373976
TI  - Histological diagnosis of hepatocellular carcinoma.
AB  - The classical morphological criteria in the diagnosis of hepatocellular carcinoma
      (HCC) include: a) the similarity of tumour cells to hepatic cord cells; b) the
      trabecular nature of the growth with capillary and canaliculi formation; and c)
      the intravascular growth of trabecular carcinoma. These criteria apply to the
      most common variants of HCC but they do not define all cases of HCC. That makes
      additional criteria and certain refinements necessary. A promising approach to
      the diagnosis of HCC is that based upon the consideration by the pathologist of
      some relevant aspects of the natural history of this tumour. A panel of tests
      exploring the various functions and properties of liver cells should be
      developed. This study provides a guideline to a dynamic approach in the diagnosis
      of HCC. The rationale is based on 5 points; among them, bile production,
      fibrinogen synthesis, Mallory body, fibrinogen G-G selection and HBV antigen
      expression can be considered at present as confident markers for the
      morphological diagnosis of HCC.

PMID- 1373977
TI  - Evidence for a lysine-specific fragmentation in fast-atom bombardment mass
      spectra of peptides.
AB  - A fragmentation process observed for peptides that contain lysine, or other amino
      acids which possess a free amino group on their sidechain, is reported. The ions
      generated by this process are found 16 Da below the acylium-type B ions that
      result from fragmentation at the C-terminal side of lysine or other amine
      containing residues in fast-atom bombardment (FAB) mass spectra. These ions,
      which are referred to as (B-16) ions, permit differentiation between the isobaric
      amino acids lysine and glutamine in peptide mass spectra. High resolution
      measurements indicate that (B-16) ions differ in composition from the
      corresponding B ions by the removal of one oxygen atom. Formation is believed to
      occur through a cyclization process initiated by nucleophilic attack by the free
      amino group of the lysine sidechain at the carbon of the acylium ion (B ion). A
      similar process initiated directly from the protonated peptide may also occur.
      Analogous cyclization processes are restricted for glutamine because this residue
      is comparatively less nucleophilic than lysine (i.e., amide vs amine). Although
      (B-16) ions have been detected under high energy collisionally induced
      dissociation, they are formed less readily than by FAB mass spectrometry. A
      mechanism consistent with this observation as well as other experimental evidence
      is presented to account for the formation of (B-16) ions.

PMID- 1373978
TI  - Matrix-assisted laser desorption using a fast-atom bombardment ion source and a
      magnetic mass spectrometer.
AB  - A conventional fast-atom bombardment (FAB) ion source was used to achieve matrix
      assisted laser desorption (MALD) in a high-mass, double-focusing, magnetic mass
      spectrometer. The pulsed ion signals generated by irradiation of a mixture of
      sample and matrix (2,5-dihydroxybenzoic acid) with either a XeF excimer laser
      (353 nm) or a nitrogen laser (337 nm) were recorded with a focal-plane detector.
      A resolution (full-width at half maximum) of 4500 was achieved at m/z 1347.7 (the
      peptide substance P), 2500 for CsI cluster ions at m/z 10,005.7, and 1250 for the
      isotope cluster of the small protein cytochrome c (horse) [M+H]+ = m/z 12,360
      (average). Sensitivity is demonstrated with 11 fmol of substance P. A survey scan
      is taken to locate the m/z of the sample molecular ion. The segment that contains
      the sample can then be integrated for a longer time to produce a better signal-to
      noise ratio. In addition to higher sensitivity and lower matrix interference, the
      advantage of MALD over FAB is the former's lower susceptibility to the presence
      of salts, and competition between hydrophobic and hydrophilic components of a
      mixture. This feature is demonstrated by the complete MALD spectrum of a crude
      partial tryptic digest of sperm-whale apomyoglobin, containing 24 peptides,
      representing the entire sequence of this protein.

PMID- 1373979
TI  - Effects of periodic backflushing on ultrafiltration performance.
AB  - Periodic backflushing was introduced to a membrane separation process to improve
      the performance. Hemoglobin (M.W. = 62,500) and dextran (M.W. = 10,000) were used
      as model compounds. Filtration performance of an ultrafiltration membrane system
      (Amicon hollow fiber membrane, H1P30-43, molecular weight cutoff = 30,000) was
      measured in terms of apparent permeability and retention coefficient of dextran
      to determine the effects of backflushing frequency and duration of one cycle. An
      optimum frequency around 0.2 min-1 existed to give a maximum permeability while
      the retention of dextran decreased with increasing frequencies. The improvement
      in permeability by periodic backflush was more than doubled. The retention of
      dextran decreased as backflushing duration was increased in one cycle. With the
      duration of 33.75 s, the retention of dextran was less than 50% and dextran
      output was 1.14 g/h, which was 1.3 times the value without backflushing. Also,
      periodic backflush made possible the long-term filtration of yeast cells for more
      than 20 h.

PMID- 1373980
TI  - Preparation of benzoyl dextran and its use in aqueous two-phase systems.
AB  - The graft modification of dextran with benzoyl groups has been studied. The
      factors that affect the degree of substitution of benzoyl dextran were
      investigated. Phase diagrams for aqueous two-phase systems composed of
      polyethylene glycol/benzoyl dextran and dextran/benzoyl dextran have been
      determined. Phase separation was also obtained in aqueous solution of two benzoyl
      dextran polymers with different degrees of substitution. A four-phase system was
      obtained with a mixture of polyethylene glycol, dextran and two kinds of benzoyl
      dextrans. The partitioning of methylene blue and a Procion yellow HE-3G dextran
      derivative were studied in polyethylene glycol/benzoyl dextran and
      dextran/benzoyl dextran two-phase systems and in systems of two benzoyl dextrans
      differing in degree of substitution. The proteins bovine serum albumin and
      glucose-6-phosphate dehydrogenase were partitioned in polyethylene glycol/benzoyl
      dextran aqueous two-phase systems and the effect of the degree of substitution of
      benzoyl dextran was studied. Chlorella pyrenoidosa, thylakoid membrane vesicles,
      plasma membrane vesicles and chloroplasts were partitioned in polyethylene
      glycol/benzoyl dextran and dextran/benzoyl dextran two-phase systems, and in a
      polyethylene glycol/dextran/benzoyl dextran four-phase system.

PMID- 1373981
TI  - Hospices and the NHS.

PMID- 1373983
TI  - Effects of neonatal enucleation on catecholamine and serotonin turnover and amino
      acid levels in lateral geniculate nucleus and visual cortex of the adult rat.
AB  - Changes in turnover of dopamine (DA), noradrenaline (NA) and serotonin (5
      hydroxytryptamine (5-HT)) and their metabolites, together with amino acid
      content, have been studied in dorsal lateral geniculate nucleus (LGNd) and visual
      cortex (VC) of neonatal enucleated rats. Enucleation increases the 5-HT turnover
      in LGNd and catecholamine turnover in VC. In contrast, enucleation decreases
      glutamate (and/or aspartate) content in LGNd and gamma-aminobutyric acid (GABA)
      in VC. These changes suggest an increase of the inhibitory action of the biogenic
      amines in LGNd after neonatal enucleation. The decrease of GABA in VC may reflect
      the importance of GABA in intracortical circuitry.

PMID- 1373982
TI  - Engraftment of leukocyte subsets following autologous bone marrow transplantation
      in acute myeloid leukemia using anti-myeloid (CD14 and CD15) monoclonal antibody
      purged bone marrow.
AB  - The cell surface phenotype of leukocyte subsets during reconstitution following
      autologous bone marrow transplantation (ABMT) using bone marrow purged with anti
      myeloid monoclonal antibodies (MoAbs) and complement (C') was evaluated in 20
      patients with acute myeloid leukemia (AML). Repopulation of B and T lymphocytes,
      natural killer (NK) cells, and myeloid cells was assessed by phenotypic analysis
      using two-color cytofluorography of peripheral blood mononuclear cells (PBMNC) at
      several time points up to 2 years post-transplantation. In spite of removal of
      the majority of monomyeloid cells of the autograft by purging with anti-CD14 and
      anti-CD 15, engraftment occurred rapidly. The myeloid cells appeared normal by
      surface phenotype. An early rise in NK cells, characterized by expression of CD57
      and CD 16, was seen. The CD4:CD8 ratio remained low throughout the study period,
      primarily due to a persistently low CD4 level. ABMT using bone marrow purged with
      the anti-myeloid MoAbs PM-81 and AML-2-23 and C' resulted in prompt engraftment
      of neutrophils. Although there was a prolonged time for recovery of lymphocyte
      subsets, this did not result in an increased risk of early infectious
      complications. Late infectious complications post-transplantation were limited to
      herpes zoster infection in one patient 18 months post-transplantation, and
      bacterial meningitis in that same patient 2 months later. This study demonstrates
      that ABMT in patients with AML using bone marrow purged with the anti-myeloid
      MoAbs PM81 (anti-CD15) and AML-2-23 (anti-CD14) and C' results in rapid
      hematologic engraftment and delayed phenotypic immunologic reconstitution without
      significant acute or chronic clinical toxicities.

PMID- 1373984
TI  - Restoration of diabetes-induced changes in enteric nerves by phorbol 12,13
      dibutyrate.
AB  - Treatment of segments of ileum from 8-week streptozotocin-induced diabetic rats
      with phorbol 12,13-dibutyrate (PDBu) in vitro resulted in restoration of the
      diabetes-induced changes in the expression of enteric VIP- and galanin-like
      immunoreactive nerve fibres. The increase in fluorescence intensity and density
      of VIP- and galanin-like immunoreactivity observed in 8-week streptozotocin
      treated rats was reduced to a near normal level after 40 min incubation of
      diabetic tissues in Krebs solution containing PDBu (100 nM). The tissue content
      of VIP was also affected (control = 2.1 +/- 0.31 pmol/cm; diabetic = 4.6 +/- 0.48
      pmol/cm; diabetic + PDBu = 2.9 +/- 0.91 pmol/cm) after incubation with PDBu. The
      significance of these findings in relation to the possible role of protein kinase
      C in the regulation of expression and/or storage of these enteric neuropeptides
      in normal and diabetic states is discussed.

PMID- 1373985
TI  - Environmental chemicals and differential stimulation of immune response.

PMID- 1373986
TI  - Localization of allergens in the domestic mite Lepidoglyphus destructor.
AB  - The non-pyroglyphid domestic mite Lepidoglyphus destructor is a major source of
      allergen causing respiratory symptoms in farming environments. This study is the
      first to focus on the localization of the allergens in the non-pyroglyphid
      domestic mite Lepidoglyphus destructor. Cryostat-cut sections of L. destructor
      mite bodies and faecal pellets were probed with one of three mouse monoclonal
      antibodies (MoAbs) raised against L. destructor or with patient sera, and stained
      with immunoperoxidase. Eight sera were RAST-positive to L. destructor and L.
      destructor faecal pellets. These eight RAST-positive patient sera labelled the
      wall of the L. destructor gut and two of them also the faecal pellets. The MoAbs
      additionally labelled parts of the exoskeleton and reacted with a majority of the
      faecal pellets. Cryostat-cut sections of Dermatophagoides pteronyssinus mite
      bodies and faecal pellets were probed with L. destructor MoAbs, which resulted in
      only slight staining of a few faecal pellets. The results suggest that at least
      one L. destructor allergen is associated with digestion.

PMID- 1373987
TI  - Application of monoclonal antibodies against major basic protein (BMK-13) and
      eosinophil cationic protein (EG1 and EG2) for quantifying eosinophils in
      bronchial biopsies from atopic asthma.
AB  - A monoclonal antibody prepared against the eosinophil major basis protein (MBP)
      was compared with the anti-eosinophil cationic protein (ECP) antibodies (EG1 and
      EG2) in immunostaining of bronchial biopsies from atopic asthma and controls.
      Anti-MBP (designated BMK-13) did not cross-react with other eosinophil basic
      proteins (i.e. ECP, eosinophil peroxidase [EPO] or eosinophil-derived neurotoxin
      [EDN]) and stained more than 98% of peripheral blood eosinophils irrespective of
      their degree of activation. EG2 stained 15% of resting and 75% of activated
      eosinophils; EG1 recognized 74% and 78% of resting and activated cells,
      respectively. The numbers of BMK-13, EG1 or EG2-positive staining cells in
      bronchial biopsies from asthma were significantly greater than atopic non
      asthmatics (P less than 0.02, P less than 0.01 and P less than 0.05,
      respectively) and normal non-atopic controls (P less than 0.001). For each of the
      various groups studied, the rank order for the number of eosinophils stained was
      BMK-13 greater than EG1 greater than EG2. BMK-13 stained significantly more cells
      from bronchial biopsies of atopic asthma and atopic non asthma when compared to
      EG2 (P less than 0.001 and P less than 0.05, respectively). Since only a
      proportion of BMK-13+ cells were EG2+, these results suggest that not all tissue
      eosinophils are actively secreting. Thus, BMK-13 can serve as a useful pan
      eosinophil marker in tissue sections since it appears to stain most eosinophils.

PMID- 1373989
TI  - Mediastinal masses in children with Hodgkin's disease. An analysis of the
      Children's Hospital of Philadelphia and the Hospital of the University of
      Pennsylvania experience.
AB  - From 1970 to 1988, 121 patients younger than 18 years of age who had newly
      diagnosed Hodgkin's disease were treated at the Children's Hospital of
      Philadelphia (CHOP) and the Hospital of the University of Pennsylvania (HUP),
      Philadelphia, Pennsylvania. Fifty-five of 79 children with mediastinal masses
      (MM) had pretreatment chest radiographs from which a mediastinal mass ratio (MMR)
      could be calculated. Within a range of MMR values, 0.25 was the best
      prognosticator for event-free survival (EFS) for all patients. In those treated
      with radiation therapy (RT) alone, the intrathoracic relapse rate was zero of
      five patients with small MM (MMR less than 0.25) versus five of eight patients
      with large MM (P = 0.09). For combined-modality therapy (CMT), there were
      intrathoracic relapses in zero of four patients with small MM versus 5 of 32
      patients with large MM (P = 0.8). For CMT, the intrathoracic relapse rates for
      those receiving more than 3500 cGy versus less than 2500 cGy were 0 of 4 patients
      and 5 of 27 patients, respectively (P = 0.8). The intrathoracic relapse rate in
      children with large MM was significantly lower for CMT than for RT (5 of 32
      patients versus 5 of 8 patients) (P = 0.02). The authors concluded that in
      pediatric Hodgkin's disease, a MM with a MMR greater than or equal to 0.25 may be
      associated with poor intrathoracic control after RT alone. Despite this, children
      with large MM treated with RT alone had an excellent overall survival rate.

PMID- 1373990
TI  - The premature beat.

PMID- 1373988
TI  - Expression of collagen, osteocalcin, and bone alkaline phosphatase in a
      mineralizing rat osteoblastic cell culture.
AB  - Rat calvaria bone cells isolated by collagenase digestion form a bone-like matrix
      which mineralizes in vitro in the presence of beta-glycerophosphate, in less than
      2 weeks. The purpose of this work was to investigate, in this mineralizing rat
      osteoblastic cell culture, the synthesis of collagen, osteocalcin, and bone
      alkaline phosphatase (ALP). The results obtained indicate (1) After 15 days in
      culture, the extracellular-matrix contains collagen type I, V, and to some extent
      type III. Metabolic labeling at day 14, during the phase of nodules
      mineralization as well as new nodules formation, shows that collagen types I and
      type V are synthesized; (2) During the phase of cell growth, no osteocalcin could
      be detected in the medium, however, at the point of nodule formation, the
      osteocalcin level reached values of 3.55 +/- 1.39 ng/ml, followed by a 30-fold
      increase after nodules became mineralized. At day 14, after metabolic labeling,
      de novo synthesized osteocalcin was chromatographed on an immunoadsorbing column.
      With urea-SDS PAGE the apparent molecular weight was determined to be 9,000
      daltons. (3) Specific activity of ALP was found to be 10 nmol/min/mg of proteins
      at cell confluence. At day 15, when nodules are mineralized, this activity was
      increased by 40-fold. The Michaelis constant was 1.58 10(-3) M/L. ALP was
      inhibited by L-homoarginine and levamisole but not by L-phenylalanine. ALP was
      shown to be heat sensitive at 56 degrees C with two slopes of
      inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1373991
TI  - Immunocytochemical localization of insulin-related peptide(s) in the central
      nervous system of the snail Helix aspersa Muller: involvement in growth control.
AB  - 1. The presence of insulin-like substances has been demonstrated by
      immunocytochemistry in the central nervous system of the snail Helix aspersa. 2.
      The immunopositivity has been observed especially in the large perikarya of the
      mesocerebral green cells [the cerebral green cells (CeGC) stained in green by the
      alcian blue:alcian yellow technique]. 3. The removal of either the mesocerebrum
      or the CeGC stops the growth of the snail and induces the increase of the
      glycogen content in the mantle edge. 4. Our results show the existence of insulin
      like material in the neurosecretory cells. Previous data having demonstrated the
      presence of specific binding sites to insulin in the cephalic ganglia of Helix
      aspersa, one may suggest that insulin could play a neuromodulatory or a
      neurotransmittory role in the central nervous system and might control the
      growth.

PMID- 1373992
TI  - Percutaneous closure of a secundum atrial septal defect and double balloon
      valvotomies of a severe mitral and aortic valve stenosis in a patient with
      Lutembacher's syndrome and severe pulmonary hypertension.
AB  - This is a 43-yr-old female presenting with recurrent atrial septal defect, closed
      surgically, 10 years prior, severe aortic and mitral stenosis, and severe
      tricuspid regurgitation. She was considered inoperable because of the severe
      pulmonary hypertension and the complexity of the disease. A percutaneous umbrella
      closure of the atrial septal defect in conjunction with mitral and aortic balloon
      valvotomies could be safely and successfully performed. After significant
      clinical and hemodynamic improvement, surgery was judged feasible, but was
      refused by the patient who suddenly expired 8 weeks later. The usefulness of
      percutaneous therapy as a rescue procedure and the management of patients with
      Eisenmenger's physiology are discussed.

PMID- 1373993
TI  - Biochemical characterization of nerve growth cones isolated from both fetal and
      neonatal rat forebrains: the growth cone particle fraction mainly consists of
      axonal growth cones in both stages.
AB  - Nerve growth cones are responsible for the exact pathway finding, and for the
      establishment of neurocytoarchitecture. To elucidate the developmental changes of
      biochemical characteristics of nerve growth cones, growth cone particle (GCP)
      fractions were isolated biochemically from embryonal day 17 (E17) rat forebrain
      and from postnatal day 5 (P5). There were no significant differences in protein
      phosphorylation pattern in a Ca(2+)-dependent manner between E17-GCP fraction and
      that of P5. As for the membrane lipid composition, molar ratios of cholesterol to
      total phospholipids were well conserved during these ages. The immunoreactivity
      to anti-synaptophysin monoclonal antibody as a marker of mature synaptic elements
      could not be detected either in E17-GCP or P5-GCP fractions. To exclude the
      possibility of the contamination of dendritic elements, RNA contents and
      immunoreactivity to anti-high molecular weight microtubule-associated protein 2
      (MAP2) monoclonal antibody were examined. RNA contents of the GCP fractions were
      extremely low compared to those of other subcellular fractions both in E17 and
      P5. No immunoreactivities to anti-MAP2 antibody were observed in either GCP
      fraction. Our results suggest that the GCP fractions, isolated from forebrains of
      E17 to P5 rat, are free from the contamination of the synaptic elements, and that
      the GCP fractions are mainly composed of axonal growth cones.

PMID- 1373994
TI  - Cell and tissue-specific expression of a heterologous gene under control of the
      myelin basic protein gene promoter in transgenic mice.
AB  - Myelin basic protein (MBP) is the second most abundant protein in CNS myelin. We
      have used transgenic mice to investigate the ability of the 5' flanking sequence
      of the mouse MBP gene to regulate the cell-type-specific- and temporal expression
      of a heterologous gene under its control. Transgenic mice were produced with a
      construct containing the bacterial chloramphenicol acetyltransferase (CAT) gene
      down-stream of the MBP 5' flanking sequence and CAT expression was monitored both
      enzymatically and histochemically. The results indicate that 1323 bp of 5'
      flanking sequence is sufficient to direct CAT expression specifically to the
      tissue and cell-type, in which MBP is normally synthesized. Additionally, this
      length of sequence also retains the ability to temporally regulate CAT levels in
      a manner analogous to endogenous MBP levels.

PMID- 1373995
TI  - Down regulation of myelin-specific mRNAs in the mechanism of hypomyelination in
      the undernourished developing brain.
AB  - The expression of myelin-specific protein genes, i.e. myelin proteolipid (PLP),
      basic (BP), and myelin associated glycoproteins (MAG) was studied in normal and
      severely undernourished 20-day-old rats. The undernutrition paradigm resulted in
      reductions of approximately 50, 25 and 65% in body weight, brain weight and brain
      myelin yield, respectively. The amount of total brain RNA was not significantly
      altered, although the amount of cyclophilin (CYC) mRNA was increased. In
      contrast, the steady-state levels of myelin specific mRNAs were significantly
      decreased by approximately 40, 20 and 40% for PLP, BP and MAG, respectively. In
      addition, polyadenylation of the PLP transcript was altered, producing an
      abnormal ratio of the 1.6 kb to the 3.2 kb PLP mRNAs. The results indicate that
      down-regulation of myelin-specific gene expression is involved in the mechanisms
      of hypomyelination in hunger disease, although the individual genes are
      differently altered. Furthermore, undernutrition may have additional effects on
      the posttranscriptional processing of the transcripts as indicated by the
      abnormal size distribution of PLP messages.

PMID- 1373996
TI  - Afferent-boundary interactions in the developing neostriatal mosaic.
AB  - The caudate-putamen (neostriatum) of the mammalian basal ganglia is composed of
      two neurochemically distinct compartments termed patch (island, striosome) and
      matrix that overall contribute to a mosaic organization. In the present study,
      the distribution of the developmentally regulated extracellular matrix molecule
      tenascin, as well as several other neural cell adhesion molecules, was examined
      in the neostriatal mosaic of the early postnatal mouse and compared with tyrosine
      hydroxylase distribution following partial destruction of the dopaminergic
      nigrostriatal projection. During normal neostriatal development, tenascin is most
      dense within the matrix compartment and highly concentrated in boundaries around
      patches. This pattern is apparent on embryonic day 18, and for the most part
      disappears by postnatal day 12. Tenascin immunoreactivity is altered in the
      neostriatum following lesions of the nigrostriatal pathway in the first postnatal
      week revealed by an overall reduced expression of this molecule and a marked
      reduction in tenascin staining of boundaries at the interface of tyrosine
      hydroxylase-rich patch and tyrosine hydroxylase-poor matrix compartments. When
      compared to tyrosine hydroxylase immunoreactivity, other cell adhesion molecules
      tested failed to show altered intensities and patterns of immunoreactivity within
      the neostriatum after similar lesions. Reduced levels of tenascin in the lesioned
      neostriatum, in register with altered levels of tyrosine hydroxylase
      immunostaining of dopaminergic inputs, suggests that axons may affect the
      expression of particular recognition molecules in their target structures. The
      fact that boundaries are malleable can be related to afferent-induced plastic
      events in the differentiation of cellular elements in the developing
      nigrostriatal system.

PMID- 1373997
TI  - Reduction of graft-versus-host reactivity after small bowel transplantation: ex
      vivo treatment of intestinal allografts with an anti-T cell immunotoxin.
AB  - A specific T lymphocyte immunotoxin was used to pre-treat small bowel grafts in
      an attempt to prevent graft-versus-host (GVH) reactivity and GVH disease in a rat
      transplant model. The immunotoxin used was a conjugate of the anti-CD5 MoAb MRC
      OX-19 with ricin A chain. The grafts were perfused ex vivo with a standard
      solution of immunotoxin followed by incubation at 4 degrees C for 1 h before
      transplantation. In a semi-allogeneic strain combination (parent to F1 hybrid
      offspring) graft treatment with immunotoxin led to a prolongation of recipient
      survival compared with groups receiving similar transplants without immunotoxin
      treatment. An additive effect on survival was observed when the host was treated
      with cyclosporin. The effect of immunotoxin was greater than that of mesenteric
      lymphadenectomy in increasing host survival. The effect of graft treatment with
      the immunotoxin on cellular migration from graft to host lymphoid tissues was
      assessed in fully allogeneic transplantation (PVG to DA). Host lymphoid tissues
      were subjected to immunohistochemical analysis using a MoAb specific for donor
      class I MHC antigens. Graft treatment with the immunotoxin led to a significant
      decrease in the number of graft cells found in host lymphoid tissues 7 days after
      transplantation. However, this effect was less marked than that achieved by graft
      mesenteric lymphadenectomy. With our current protocol graft treatment with a
      specific T cell immunotoxin can significantly reduce but not abolish GVH
      reactivity in rat small bowel transplantation.

PMID- 1373999
TI  - Purification of primary antibodies of the myelin basic protein antibody cascade
      from multiple sclerosis patients. Immunoreactivity studies with homologous and
      heterologous antigens.
AB  - Previous research has demonstrated a myelin basic protein (MBP) antibody cascade
      in cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. The purpose of
      this study was to determine whether primary antibodies to MBP (anti-MBP) reacted
      similarly with homologous (human) and heterologous (bovine and porcine) MBP.
      Myelin basic protein was prepared from central nervous system white matter of
      humans as well as bovine and porcine species. Immunoglobulin G (IgG) was purified
      by protein A-Sepharose affinity chromatography from concentrated CSF of MS
      patients with active or inactive disease or from non-MS controls. Antibodies to
      MBP were isolated from purified CSF IgG of MS patients with acute relapses by two
      step antigen specific (MBP-Sepharose) affinity chromatography. Anti-MBP in the
      context of whole CSF, in purified CSF-IgG or as purified antibody, reacted
      identically with homologous and heterologous MBP. Kinetic studies of anti-MBP
      titers demonstrated that when anti-MBP was reacted in vitro with increasing
      amounts of homologous or heterologous MBP, the antibody was equally neutralized
      by either antigen. Neutralization of anti-MBP by homologous and heterologous MBP
      or their synthetic peptides may also be possible in vivo as a potential
      therapeutic tool.

PMID- 1373998
TI  - Induction of endogenous retroviral gene product (SU) as an acute-phase protein by
      IL-6 in murine hepatocytes.
AB  - The effect of Lps locus and IL-6 on the production of SU (previously termed
      gp70), a mouse endogenous retroviral gene product, was studied. Back-cross
      studies using the progeny between (NZB x C3H/HeJ)F1 and C3H/HeJ mice indicate
      that the basal level of SU is not associated with the Lps locus on chromosome 4.
      Lipopolysaccharide (LPS) mitogen response-negative mice did not show the
      enhancement of serum SU production after LPS injection. Spleen cells from LPS
      mitogen response-positive but not from negative mice showed increase of IL-6
      synthesis in the presence of LPS. Since IL-6 may be involved in the production of
      serum SU, we tested the effect of IL-6 in a primary hepatocyte culture system. SU
      production was clearly enhanced in the presence of recombinant IL-6, indicating
      that IL-6 induced by LPS can enhance the expression of retroviral genome.

PMID- 1374000
TI  - Analysis of direct tissue isoelectric focused protein profiles of resected
      intestinal mucosa and endoscopic biopsies from patients with inflammatory bowel
      disease.
AB  - Direct tissue isoelectric focusing was used as a procedure to analyze differences
      in soluble tissue protein profiles of resected intestinal segments and endoscopic
      biopsies from patients with ulcerative colitis, Crohn's disease, and colonic
      cancer. Extraction of tissue proteins was accomplished by electrophoresis of
      mucosal cryostat sections on agarose gels across a broad pH gradient. The
      inflamed colonic mucosa from Crohn's disease patients showed similar isoelectric
      focusing protein patterns. Small bowel mucosa from a patient with both colonic
      diverticular disease and Crohn's disease showed protein patterns identical with
      that of the mucosa from a patient with only Crohn's disease. The inflamed mucosae
      from ulcerative colitis patients revealed identical protein patterns but were
      distinct from those of non-inflamed ulcerative colitis mucosa and from the
      inflamed mucosae from Crohn's disease patients. Non-inflamed small bowel mucosae
      from cancer, ulcerative colitis, and Crohn's disease patients showed distinct
      protein patterns which were absent in the non-inflamed large bowel mucosae. The
      inflamed resected ileum of a Crohn's disease patient exhibited protein patterns
      similar to those of the biopsy of an inflamed mid-transverse large bowel. Mucosal
      biopsies from inflamed sigmoid colon of a Crohn's disease patient showed
      different protein patterns than those in biopsies from the inflamed mid
      transverse colon. Thus, distinctive isoelectric focusing protein patterns may be
      useful in differentiating Crohn's colitis and ulcerative colitis when granulomata
      are absent, and in resolving indeterminant colitis to one of these classic
      inflammatory bowel diseases.

PMID- 1374001
TI  - Visual associative agnosia and optic aphasia. A single case study and a review of
      the syndromes.
AB  - The case is presented of a patient who showed visual naming disturbances caused
      by a left occipital infarction. His performance on tests of visual naming, of
      recognition not requiring a verbal response, and of verbal-visual matching
      demonstrated a wide range of qualitatively different errors, including complete
      inability to recognize the object, access to partial semantic knowledge, and mere
      name finding difficulty. On the basis of the present case and of a review of the
      recent literature, the clinical distinction between visual associative agnosia
      and optic aphasia and the relation of these disorders with the anatomical site of
      lesion are discussed.

PMID- 1374002
TI  - Process of forgoing life-sustaining treatment in a university hospital: an
      empirical study.
AB  - OBJECTIVES: The difficult decision to forgo (withhold or withdraw) life
      sustaining treatment has received extensive commentary. Little attention has been
      paid to how physicians do, and should, care for dying patients once this decision
      is made. This study describes the characteristics of patients who forgo
      treatment, determines the range and sequential process of forgoing treatment, and
      suggests ethical and public policy implications. DESIGN: The charts of all
      patients who died at the University of Minnesota Hospital during a 2-month period
      were reviewed. The patient information that was collected included age and sex,
      diagnoses, mental status, location in the hospital length of hospital stay,
      method of payment, the timing of the first decision to forgo treatment, and the
      range and sequence of interventions forgone. SETTING: All ICUs and general wards
      in a 586-bed tertiary care university hospital. PATIENTS: All patients who died
      at the University of Minnesota Hospital during May and June 1989. MAIN RESULTS: A
      total of 52 (74%) of 70 patients who died had some intervention withheld or
      withdrawn before death. Those patients in whom treatment was forgone were more
      likely to have an underlying malignancy or impaired mental status and longer
      hospital stays. Thirty-two (62%) of 52 patients who declined some treatment were
      in an ICU; 26 (50%) of 52 patients required mechanical ventilation. On average,
      5.4 separate interventions were forgone per patient. Resuscitation and/or
      endotracheal intubation were generally the first measures withheld; once a
      patient required a ventilator, withdrawing the ventilator was a late decision.
      Precise methods of ventilatory and vasopressor withdrawal varied considerably
      among patients. CONCLUSIONS: Forgoing life-sustaining treatment is not a single
      decision but it often occurs in a sequential manner over several days. A strict
      analysis of the benefits and burdens of various interventions may be inadequate
      in deciding what interventions are appropriate in the care of the dying patient.

PMID- 1374003
TI  - Increased sensitivity to mechanical ventilation after surfactant inactivation in
      young rabbit lungs.
AB  - OBJECTIVES: To study the individual and combined effects of surfactant
      inactivation and mechanical ventilation on pulmonary microvascular permeability
      and lung compliance. DESIGN: Prospective, controlled trial. An isolated,
      perfused, lung model of surfactant inactivation and mechanical ventilation at 15,
      30, and 45 cm H2O peak inspiratory pressure was developed in young (4 to 6 wks)
      New Zealand white rabbits. SETTING: Laboratory of a university-affiliated medical
      school. MEASUREMENTS AND MAIN RESULTS: Isolated, perfused lungs were prepared for
      measurement of the capillary filtration coefficient before and after one of four
      interventions: instillation of dioctyl succinate, a surfactant inactivator,
      without ventilation (group 1); ventilation without dioctyl succinate at 15, 30,
      or 45 cm H2O peak inspiratory pressure (group 2); ventilation after dioctyl
      succinate pretreatment at 15, 30, or 45 cm H2O peak inspiratory pressure (group
      3); and control lungs without dioctyl succinate or ventilation (group 4). A
      significant increase in the capillary filtration coefficient was noted after
      dioctyl succinate treatment alone, after ventilation alone at 45 cm H2O peak
      inspiratory pressure, and after dioctyl succinate plus ventilation at 15, 30, and
      45 cm H2O peak inspiratory pressure. Dioctyl succinate plus ventilation produced
      a significantly greater increase in the capillary filtration coefficient than
      ventilation alone at 15 and 45 cm H2O peak inspiratory pressure. CONCLUSIONS:
      These data suggest that ventilation after surfactant inactivation is more
      injurious to the pulmonary microvasculature than ventilation alone, and that
      generalized lung overdistention is not the primary mechanism for microvascular
      injury in the diseased, noncompliant lung. The increases seen in the capillary
      filtration coefficient in postventilated surfactant inactivated lungs, even at
      low-ventilation pressures, suggest that low peak inspiratory pressures do not
      overdistend the dioctyl succinate-treated lung.

PMID- 1374004
TI  - Bleomycin-induced acute lung injury in the rat does not influence pulmonary
      vascular responsiveness in vitro.
AB  - OBJECTIVE: To investigate the effects of the intratracheal and iv administration
      of bleomycin on the contraction and endothelially dependent vasodilation of rat
      pulmonary arteries in vitro. DESIGN: Prospective pharmacologic study. SETTING:
      National Heart and Lung Institute, London, UK. INTERVENTIONS: Intratracheal
      saline, intratracheal and iv bleomycin. MEASUREMENTS AND MAIN RESULTS: Rats
      treated with intratracheal bleomycin developed a significant increase in mean
      lung wet/dry weight ratio (5.6 +/- 0.4 [SEM] vs. 3.9 +/- 0.1, p less than .05)
      when compared with saline-treated control animals, confirming the development of
      pulmonary edema. However, these rats displayed normal relaxant responses to the
      endothelially dependent vasodilator acetylcholine and a normal contractile
      response to phenylephrine in vitro. Intravenous bleomycin had no effect on either
      wet/dry weight ratio or the response to either drug. CONCLUSIONS: Despite
      evidence for the loss of endothelial integrity that characterizes lung injury
      after intratracheal bleomycin, isolated pulmonary artery rings in vitro showed no
      loss of endothelial cell function. The role of the endothelium in modulating
      pulmonary ventilation/perfusion matching after lung injury is unclear.

PMID- 1374005
TI  - Expression and cellular distribution of the alpha 1 gap junction gene product in
      the ocular pigmented ciliary epithelium.
AB  - The expression of four different gap junction (GJ) transcripts, corresponding to
      the alpha 1, alpha 3, beta 1 and beta 2 gene products, has been examined in the
      ciliary epithelium of human and bovine eyes, and in cultures of ciliary
      epithelial cells. Northern blot analysis revealed that alpha 1 mRNA, 3.6-kb in
      size, was the predominant transcript expressed in intact tissue and in cultures
      of pigmented ciliary epithelial cells (PE). No transcripts from the alpha 3, beta
      1 or beta 2 gap junction genes were detected in intact tissue or ciliary
      epithelial cells as demonstrated by Northern blotting. When the levels of alpha 1
      gap junction mRNA were compared between PE and NPE in primary cultures, a
      striking difference was observed in the level of alpha 1 transcripts: there was
      about a 6 to 8-fold increase in alpha 1 levels in PE cells, relative to the NPE
      cells. To verify the differential level of expression of alpha 1 GJ mRNA in the
      two cell types, indirect immunofluorescence localization studies were performed
      on semithin cryostat sections of ciliary processes. These studies revealed that
      alpha 1 gap junctions are present at the apical and lateral borders of PE cells,
      i.e. at the apical plasma membranes domains of PE-NPE cells, and at the lateral
      plasma membrane regions of PE-PE cells borders. Further analysis by
      immunoblotting confirmed that the 43 kD alpha 1 gap junction protein was the
      major gap junction gene product in the ciliary epithelium.

PMID- 1374007
TI  - Tissue-specific expression of insulin-like growth factor binding protein-3
      protease activity during rat pregnancy.
AB  - The abundances of insulin-like growth factor binding proteins (IGFBPs) in sera
      and tissue homogenates of rats at days 12, 15, and 18 of pregnancy were
      determined by ligand- and immunoblotting. As in serum, IGFBP-3 was abundant in
      day 12 uterus, placenta, and fetuses, and decreased by day 15. On day 18 of
      pregnancy, IGFBP-2 was predominant and IGFBP-3 was less than 25% of day 12 values
      in fetus and placenta, and was undetectable in uterus and decidua. In contrast,
      IGFBPs in the nonreproductive tissues did not change significantly. IGFBP-3 was
      more abundant in muscle than heart and liver, and was not detected in lung,
      kidney, or brain. The decrease in IGFBP-3 in serum and reproductive tissues
      between days 12 and 15 of pregnancy was temporally related to the appearance of
      IGFBP-3 protease activity. Proteolytic activity was detectable only at low levels
      in brain, liver, and spleen, and was undetectable in lung, heart, muscle, and
      kidney. The specific protease inhibitors that blocked IGFBP-3 proteolytic
      activities in pregnant rat serum and decidua were virtually identical and
      suggested inhibition of a divalent cation-dependent tryptic-like serine protease.
      Furthermore, exposure of bovine IGFBP-3 (in nonpregnant bovine serum) or
      radiolabeled recombinant human IGFBP-3 to day 18 pregnant rat serum, decidua or
      uterus resulted in the generation of IGFBP-3 fragments with the same apparent Mrs
      (29-31 K and 18-23 K). We postulate that tissue-specific degradation may be as
      important as synthesis in determining IGFBP-3 abundance, and that the dramatic
      changes in IGFBPs in reproductive and fetal tissues may cause changes in IGF
      availability which are necessary for rapid tissue growth and differentiation.

PMID- 1374006
TI  - Phenotypic alterations in fibroblasts and fibrosarcoma cells that overexpress
      latent transforming growth factor-beta 1.
AB  - Mouse embryo-derived AKR-2B fibroblasts and murine fibrosarcoma cells (the 1591
      cell line) were transfected with a murine transforming growth factor-beta 1 (TGF
      beta 1) cDNA under the transcriptional control of either the simian virus-40
      early promoter or the cytomegalovirus promoter/enhancer. Selected clones secreted
      2- to 4-fold more TGF beta-competing activity into their media than the parental
      cell line or neomycin-transfected controls. The TGF beta 1 released into the cell
      conditioned medium was latent. Despite the latency of the overexpressed TGF beta
      1, TGF beta 1-transfected cells exhibited phenotypic features of TGF beta 1
      treated cells. When confluent, the TGF beta 1-transfected cells had the
      morphological characteristics of the parental cells that have been treated with
      active TGF beta 1. AKR-2B cells that expressed higher levels of TGF beta 1 also
      expressed high levels of c-sis and c-myc mRNAs and decreased TGF beta 2 and TGF
      beta 3 mRNAs in the same manner as parental AKR-2B cells that had been treated
      with active TGF beta 1. The transfected 1591 cells that overexpressed TGF beta 1
      bound less [125I]TGF beta 1 than did parental 1591 cells, but after a mild acid
      wash demonstrated an increase in [125I]TGF beta 1 binding. Our results suggest
      that these TGF beta 1-transfected fibroblast and fibrosarcoma cells have the
      capacity to activate TGF beta; however, as very little activated TGF beta is
      detected in the medium, it is hypothesized that these cells activate latent TGF
      beta 1 and bind the activated TGF beta 1, thus acquiring a phenotype consistent
      with TGF beta 1-treated cells.

PMID- 1374008
TI  - Differentiation-controlled synthesis and binding of thrombospondin to granulosa
      cells.
AB  - Thrombospondin (TSP) is a large glycoprotein, synthesized by several matrix
      forming cells and incorporated into their extracellular matrix. In several cell
      types its presence supports cell growth and proliferation. To investigate the
      role of this protein in cell differentiation, we studied the hormonal effect of
      TSP production and receptor-mediated binding to primary granulosa cells prepared
      from diethylstilbestrol-treated immature female rats. These cells can be induced
      to differentiate by FSH, 8-bromo-cAMP (8-Br-cAMP), or forskolin. Progesterone
      production is induced during differentiation, and its level of synthesis is an
      important manifestation of the differentiated phenotype. We find that
      undifferentiated granulosa cells synthesize and secrete TSP. The protein
      comprises about 0.5% of the total cell protein, and it is the major protein
      secreted in culture. Treatment of the cells with FSH or 8-Br-cAMP reduces TSP
      production dramatically, and forskolin completely inhibits it. In parallel, we
      observed that the undifferentiated cells bind TSP specifically with a Kd of 1.8
      nM, and the number of binding sites per cell is 1.7 x 10(5). This binding can be
      prevented by excess TSP or an anti-TSP monoclonal antibody (B7-3). This ability
      to bind TSP is completely lost after induction of differentiation by FSH or 8-Br
      cAMP. Our findings show that both the production and binding of TSP to granulosa
      cells are tightly controlled by normal cell differentiation and indicate that
      changes in TSP are correlated with the passage of the cell through the stages of
      maturation, a passage that also involves changes in cell shape and extracellular
      interactions and in the steroidogenic capacity of these cells.

PMID- 1374009
TI  - Adenosine 3',5'-monophosphate and thyroid hormone control of uncoupling protein
      messenger ribonucleic acid in freshly dispersed brown adipocytes.
AB  - We intend to develop in vitro model systems to study the hormonal regulation of
      uncoupling protein (UCP) and its role in brown adipose tissue (BAT)
      thermogenesis. We report here that UCP mRNA responses to adrenergic and thyroid
      hormone manipulations in freshly dispersed, mature brown adipocytes mimic in vivo
      observations. Studies were performed in brown adipocytes obtained from
      interscapular brown fat of euthyroid or hypothyroid rats. The tissue was
      dispersed with collagenase, and cells were isolated by floatation over 4% BSA.
      UCP mRNA in these cells is 2-3 times more abundant than that in the whole tissue,
      indicating a selection of cells expressing the gene. In cells from euthyroid
      rats, UCP mRNA is maximally elevated within 2 h of exposure to 1 microM forskolin
      and 50 ng T3/ml (77 nM total, 0.43 nM free). T3 significantly enhances the effect
      of forskolin. In the absence of stimulation, UCP mRNA rapidly disappears from
      euthyroid brown adipocytes, and this can be prevented with the addition of T3 by
      a mechanism not requiring on-going transcription. In cells from hypothyroid rats,
      forskolin or isoproterenol plus phenylephrine fail to stimulate UCP mRNA, but
      within 3 h of exposure to T3, cells recover full responsiveness. As in vivo, a
      high extracellular concentration of T3 is required for maximal responsiveness of
      UCP mRNA to cAMP, while T4 can restore responsiveness in physiological
      concentrations (40 pM). This effect of T4 is prevented by iopanoic acid, a
      compound that blocks the type II T4 5'-deiodinase. In conclusion, 1) freshly
      dispersed brown adipocytes retain all of the properties concerning UCP regulation
      by thyroid hormone and sympathetic nervous system described for brown fat in
      vivo; 2) the observations made in vivo, thus, represent direct action of
      norepinephrine and thyroid hormone on these cells; 3) as in vivo, T4 is a better
      source of intracellular T3 than extracellular T3 for brown adipocytes; hence, the
      in vivo findings are the result of the cell biology of 5'-deiodinase type II
      rather than dynamic factors inherent to the in vivo condition; 4) stabilization
      of mature UCP mRNA by T3 is an important mechanism to maintain the levels of this
      mRNA elevated under sustained stimulation; and 5) dispersed brown adipocytes and
      UCP gene products constitute a powerful model to study interactions between the
      sympathetic nervous system and thyroid hormone at a cellular or molecular level.

PMID- 1374010
TI  - Expression of steroidogenic enzymes in the bovine placenta and fetal adrenal
      glands throughout gestation.
AB  - The expression of cholesterol side-chain cleavage cytochrome P450 (P450scc), 17
      alpha-hydroxylase cytochrome P450 (P45017 alpha), and 3 beta-hydroxysteroid
      dehydrogenase (3 beta HSD) was studied in bovine placenta and fetal adrenal
      glands throughout gestation. The levels of expression of these enzymes were much
      lower in the placenta than in the adrenals by Western and Northern analyses. The
      levels of P450scc, however, remained relatively constant in bovine placenta and
      fetal adrenal glands at all gestational stages studied. In contrast, P45017 alpha
      expression was higher in both the placenta and the fetal adrenal glands during
      the early stages of pregnancy, but declined markedly in both tissues through the
      period of midgestation. The expression of P45017 alpha increased markedly in the
      fetal adrenal glands in late gestation. The levels of 3 beta HSD were extremely
      low in placental tissues, but were higher in the fetal adrenals, where they were
      found to be slightly elevated in early and late gestation compared to those in
      midgestational stages. Immunocytochemical examination of the levels of P45017
      alpha and 3 beta HSD in the fetal adrenal glands correlated with the results of
      Western and Northern analyses. In addition, the morphology and distribution of
      these two enzymes in the developing bovine fetal adrenal glands indicated that
      while the early activated gland is functional relative to the ability to secrete
      steroids, structural and functional organization more typical of mature adrenal
      glands is not achieved until the time of activation of the fetal adrenals in late
      gestation.

PMID- 1374011
TI  - Estrogen control of uterine tissue factor messenger ribonucleic acid levels.
AB  - One of the early responses of the immature rat uterus to stimulation by estradiol
      (E2) is an increase in the specific activity and synthesis of a discrete set of
      proteins including tissue factor (TF). Increases in TF are associated with
      stimulation of cell growth in mouse and human fibroblasts and endothelial cells.
      The increase in TF activity following E2 stimulation of the uterus is due to an
      increase in TF messenger RNA (mRNA). A 2- to 4-fold increase in mRNA is observed
      1 h after injection, reaches a maximum at 3 h, and is reduced at 6 h. The
      increase is hormone specific and occurs at low levels of E2 (0.66 micrograms/kg).
      The E2 effect is abolished by actinomycin but not by cycloheximide. The changes
      in TF mRNA occur in a similar time scale and at similar E2 doses as the increases
      in the uterine proto-oncogenes c-jun and c-fos.

PMID- 1374012
TI  - The interaction of heparin and basic fibroblast growth factor on collagen
      synthesis in 21-day fetal rat calvariae.
AB  - We examined the interactions of the glycosaminoglycan, heparin, and recombinant
      human basic fibroblast growth factor (bFGF) on collagen synthesis in 21-day fetal
      rat calvariae. In calvariae treated for 96 h, heparin (25 micrograms/ml) and bFGF
      (10(-9) M) inhibited collagenase-digestible protein (CDP) labeling by 52 and 60%
      of control, respectively, and the combination further inhibited CDP labeling.
      Inhibition of CDP labeling by heparin (25 micrograms/ml) or bFGF (10(-9), 10(-8)
      M) was similar in the presence or absence of aphidicolin (30 microM) an inhibitor
      of cell replication. Heparin selectively inhibited CDP labeling in the osteoblast
      rich central bone but bFGF alone or in combination with heparin inhibited CDP
      labeling both in the periosteum and central bone. Heparin and bFGF alone
      decreased steady state levels of alpha 1(I)procollagen messenger RNA (mRNA) at 24
      h and the combination further decreased mRNA levels. A high concentration of
      insulin-like growth factor-1 (IGF-1, 3 x 10(-8) M) reversed the inhibitory effect
      of heparin on DNA synthesis and CDP labeling. In contrast, IGF-1 could not
      reverse the inhibitory effects of bFGF on CDP labeling but enhanced the
      stimulatory effects of bFGF on thymidine incorporation into DNA. We conclude that
      the inhibitory effects of heparin and bFGF on CDP are independent of effects on
      cell replication. We further conclude that both heparin and bFGF inhibit collagen
      synthesis at a pretranslational site since they decreased procollagen mRNA levels
      in osteoblasts. However, the inhibition of collagen synthesis by heparin and bFGF
      appears to involve divergent pathways since exogenous IGF-1 could overcome the
      effect of heparin but not bFGF on collagen synthesis.

PMID- 1374013
TI  - Expression of insulin-like growth factor-binding protein-2 and -3 messenger
      ribonucleic acid in the porcine ovary: localization and physiological changes.
AB  - Insulin-like growth factor-binding protein (IGFBP)-2 and -3 are the most
      prevalent IGFBPs in porcine follicular fluid, as determined on ligand blots, but
      little is known about the localization and regulation of their synthesis in vivo.
      This study was designed to investigate the localization and cyclic regulation of
      the mRNA for these two IGFBPs in the porcine ovary, RNA was extracted from whole
      ovaries morphologically classified as immature, preovulatory, and luteal.
      Northern hybridization analysis of this RNA showed no significant difference in
      the expression of IGFBP-2 mRNA in these ovaries (OD for preovulatory, luteal, and
      immature ovaries, 0.076 +/- 0.01, 0.071 +/- 0.01, and 0.10 +/- 0.008/micrograms
      RNA, respectively). IGFBP-3 mRNA was not different in immature and preovulatory
      ovaries, but was 10-fold greater (P less than 0.025) in luteal ovaries. Northern
      analysis of RNA extracted from ovaries also showed no significant change in IGFBP
      2 mRNA on days (d) 11, 16, and 21 of the estrous cycle. IGFBP-3 mRNA tended to
      decrease between d11-16 with the onset of luteal regression and was significantly
      decreased in d21 preovulatory ovaries to 22% of the values in d11 ovaries.
      Granulosa, thecal, and luteal cells were also analyzed for IGFBP mRNA. IGFBP-2
      mRNA was most abundant in granulosa cells, lower in thecal cells, and lowest in
      luteal cells. No IGFBP-3 mRNA could be detected in granulosa cells, and luteal
      cells expressed 15- to 63-fold greater levels than thecal cells. These results
      show that IGFBP-2 and -3 mRNAs are expressed in specific ovarian cell types and
      that their expression appears to be independently regulated during the
      reproductive cycle. This provides further evidence for the importance of these
      proteins as paracrine/autocrine regulators of ovarian function.

PMID- 1374015
TI  - Ovine placental lactogen is a potent somatogen in the growth hormone (GH)
      deficient rat: comparison of somatogenic activity with bovine GH.
AB  - The somatogenic effects of recombinant ovine placental lactogen (oPL) were
      investigated in the GH-deficient dwarf rat and compared to those of identical
      doses of recombinant bovine GH (bGH) in three independent studies. Both oPL and
      bGH treatments resulted in an increase (P less than 0.05) in body weight gain
      compared to that in saline controls, with oPL treatment being more potent than
      bGH (P less than 0.05). In promoting linear growth, oPL was more potent (P less
      than 0.05) than bGH in some instances. The nitrogen content of dry carcass matter
      was increased with oPL treatment compared to saline (P less than 0.05), with a
      nonsignificant increase in bGH-treated animals. Carcass fat was similarly reduced
      by both oPL and bGH treatment (P less than 0.05) compared to saline. Serum
      insulin-like growth factor-I (IGF-I) concentrations were increased significantly
      (P less than 0.05) by both oPL and bGH treatments, with a significantly greater
      effect of oPL suggested in one study. No increase in hepatic IGF-I mRNA was
      evident with either treatment, suggesting that the increase in serum IGF-I is due
      to posttranscriptional mechanisms. The expression of IGF-binding protein-3
      hepatic mRNA was increased (P less than 0.05) with bGH treatment compared to that
      after saline treatment, but was unaffected by oPL treatment, indicating
      regulation by GH at the transcriptional level. The binding of [125I]bGH to
      hepatic membrane preparations demonstrated no difference in specific binding
      compared to that in saline controls. However, [125I]oPL specific binding was
      greater in oPL-treated animals (P less than 0.05). Animals treated with bGH had
      reduced (P less than 0.05) hepatic GH receptor mRNA compared to saline controls,
      but oPL treatment had no effect. Thus, oPL is a potent anabolic and lipolytic
      agent in the dwarf rat, exerting greater somatogenic effects on some parameters
      than bGH. Our data suggest differences in receptor binding and effects on GH
      receptor and IGF-binding protein-3 expression with these two treatments, raising
      the possibility of actions through different pathways or differential effects at
      the GH receptor level.

PMID- 1374014
TI  - Cyclic adenosine 3',5'-monophosphate negatively regulates clusterin gene
      expression in Leydig tumor cell lines.
AB  - The clusterin protein and its messenger RNA were identified in many tissues
      including testis. In this report, we demonstrate the expression of clusterin gene
      in four Leydig tumor cell lines, including mouse MA-10 and I-10 and rat R2C and
      LC-540. When the cells were incubated with 0.1 mM 8-bromo-cAMP or (Bu)2cAMP for
      17 h, an unexpected, profound suppression of clusterin mRNA accumulation was
      observed. A 60-70% decrease in clusterin mRNA was observed in MA-10 and R2C
      cells, 10% in I-10 cells, and no apparent change in LC-540 cells. The inhibitory
      effect of cAMP was specific to the clusterin gene, since in the same cells
      cholesterol side-chain cleavage enzyme mRNA was drastically elevated in MA-10 and
      I-10 cells while alpha-tubulin mRNA levels were not changed in all four cell
      lines. The reduction could be detected as early as 4 h, and was evident at 17 h
      after cAMP administration. Removal of cAMP from culture media at 17 h prevented
      the decline of clusterin mRNA. The suppression of clusterin gene expression can
      also be demonstrated by treatment with human CG or forskolin, which were known to
      elevate intracellular cAMP levels. Our observations suggest: 1) cAMP negatively
      regulates clusterin gene expression in two Leydig tumor cell lines, MA-10 and
      R2C; 2) The inhibitory effect of cAMP on clusterin gene expression is probably
      acting through the protein kinase A pathway; and 3) The four Leydig tumor cell
      lines respond differently to cAMP in the expression of clusterin and side-chain
      cleavage genes.

PMID- 1374017
TI  - Body growth, carcass composition, and endocrine changes in lambs chronically
      treated with recombinantly derived insulin-like growth factor-I.
AB  - Castrate yearling male sheep were treated for 8 weeks with either 50
      micrograms/kg body wt/8 hourly sc insulin-like growth factor-I (IGF-I) (n = 10)
      or with saline (n = 9). IGF-I treatment increased plasma IGF-I from 235 +/- 17 to
      347 +/- 16 ng/ml (P less than 0.001). There was a gradual divergence in body wt
      (P less than 0.10) between treatment groups. Food intake did not change
      significantly. The weight of the spleen corrected for body wt increased by 40% (P
      less than 0.001) and there was a marginal increase in adjusted kidney wt (P less
      than 0.1). There was no effect of IGF-I on carcass weight or dimensions, or on
      long bone length, although the weight per unit length of the tibia (P less than
      0.05) and femur (P less than 0.10) were increased. There was no effect on wool
      growth. Plasma IGF binding proteins (IGFBPs) were quantified by ligand blot
      analysis. In the IGF-I treated group, IGFBP-1 showed a transient increase (P less
      than 0.05) at day 3 but was similar in both groups at day 55 of treatment. IGFBP
      2 was suppressed (P less than 0.05) by day 55 and IGFBP-3 and 4 did not change.
      Plasma glucose was elevated (P less than 0.05) and plasma insulin was suppressed
      (P less than 0.01) from 280 +/- 32 pg/ml to 124 +/- 30.4 pg/ml, plasma urea (P
      less than 0.01) and creatinine (P less than 0.05) were reduced in the IGF-I
      treated group. The somatogenic effect of IGF-I in this study was minimal
      suggesting that in the well fed animal with an intact somatotropic axis IGF-I
      treatment at doses which double plasma IGF-I does not enhance somatic growth
      performance. However, the marked splenomegaly shows the sensitivity of splenic
      growth to systemic IGF-I. The suppression of insulin with chronic IGF-I treatment
      was accompanied by hyperglycaemia--this may explain in part the lack of a
      significant anabolic response and may limit the utility of IGF-I therapy unless
      higher doses with insulin-like effects are used.

PMID- 1374016
TI  - Galanin inhibits proinsulin gene expression stimulated by the insulinotropic
      hormone glucagon-like peptide-I(7-37) in mouse insulinoma beta TC-1 cells.
AB  - The neuropeptide hormone galanin, released by sympathetic stimulation of nerve
      terminals in the endocrine pancreas, inhibits insulin secretion via a receptor
      linked pertussis toxin-sensitive (Gi) transmembrane signaling pathway. Glucagon
      like peptide-I(7-37) [GLP-I(7-37)] is an intestinal hormone shown to have potent
      insulin-releasing activities in pancreatic B-cells and is believed to serve a
      physiological role in the augmentation of nutrient-induced insulin release. GLP
      I(7-37) binds to specific Gs- and adenylate cyclase-coupled receptors on
      pancreatic B-cells and directly stimulates proinsulin gene transcription, thereby
      increasing cellular levels of proinsulin messenger RNA (mRNA) and proinsulin
      biosynthesis. This study examines the effects of galanin on GLP-I(7-37)
      stimulated proinsulin gene expression in mouse beta TC1 cells. The degree of
      proinsulin gene transcription was assessed by measuring the activity of
      chloramphenicol acetyl transferase (CAT) expressed from a CAT reporter plasmid
      linked to the rat insulin-1 gene promoter transferred to beta TC1 cells and by
      measuring proinsulin mRNA levels by Northern blot analysis. Galanin inhibited
      both CAT activity and the rise in proinsulin mRNA levels stimulated by either GLP
      I(7-37) or forskolin (0.1 microM). Notably, galanin was without effect on CAT
      activity induced by the cAMP analog, 8-bromo-cAMP, the phosphodiesterase
      inhibitor 3-isobutyl-1-methylxanthine, or higher concentrations of forskolin. The
      inhibitory effects of galanin on GLP-I(7-37) and forskolin-induced CAT activity
      were reversed by the addition of pertussis toxin, a toxin that inactivates
      inhibitory G-proteins (Gi). We conclude that galanin inhibits GLP-I(7-37)
      stimulated proinsulin gene expression by inhibiting the activation of adenylate
      cyclase by GLP-I(7-37) and subsequently the production of cAMP in B-cells.
      Further, our data suggest that these actions of galanin are mediated by a
      pertussis toxin sensitive pathway involving one or more Gis that inhibit
      adenylate cyclase. Thus, in addition to its well known inhibitory effects on
      insulin secretion galanin can inhibit proinsulin gene expression stimulated by
      GLP-I(7-37) activation of the cAMP signaling pathway. These findings may be a
      unique demonstration of the inhibition of proinsulin gene expression by a
      substance (galanin) released endogenously within the pancreas.

PMID- 1374018
TI  - Basic fibroblast growth factor: a potential mediator of stromal growth in the
      human prostate.
AB  - Studies were undertaken, using isolated prostatic epithelial and stromal cells,
      to evaluate the role of basic fibroblast growth factor (bFGF) in the regulation
      of benign prostatic growth. bFGF was detected in lysates, but not the conditioned
      media, of cultured prostatic epithelial and stromal cells by Western
      immunoblotting and immunoprecipitation of metabolically labeled proteins.
      Immunofluorescence analysis of benign human prostate localized the majority of
      bFGF to the prostatic stroma. In addition, bFGF was a potent stimulator of
      stromal cell proliferation in vitro, but was not mitogenic to cultured epithelial
      cells. Further studies demonstrated bFGF receptors (Kd = 258 pM; 61,400
      receptors/cell) on stromal cells, but not epithelial cells. Epithelial cell
      conditioned medium was mitogenic for stromal cells, suggesting the presence of
      paracrine interactions. However, bFGF does not appear to be the mediator of this
      interaction, since the mitogenic effect of epithelial cell-conditioned medium on
      stromal cells was not significantly reduced by the addition of anti-bFGF.
      Additional studies showed that concentrated stromal cell-conditioned medium was
      not mitogenic to cultured stromal cells under serum-free defined conditions,
      indicating the lack of an external autocine mechanism. These studies demonstrate
      that bFGF is actively synthesized by isolated prostatic epithelial and stromal
      cells, but is largely not secreted. Prostatic stroma, but not epithelia, are
      responsive to the mitogenic effect of bFGF in vitro. However, because of the
      limited secretion of bFGF by prostatic cells, the mechanism(s) of bFGF-mediated
      regulation of stromal growth remains unclear.

PMID- 1374019
TI  - Growth hormone (GH) regulation of gastric structure and function in the GH
      deficient rat: up-regulation of intrinsic factor.
AB  - In a recent study we identified GH receptor/binding protein in cells of the
      gastric mucosa. In order to define the role of the GH receptor/binding protein in
      gastric function, we have investigated the effect of GH on gastric structure and
      function in the GH-deficient Lewis (dwarf) rat. Bovine GH, 65 micrograms/100 g
      body wt, was administered twice daily to adult male dwarf rats for 6 days (DW+)
      while control animals received vehicle only (DW-). Administration of GH produced
      a significant increase in body wt (P less than 0.001), stomach wt (P less than
      0.01), and stomach to body wt ratio (P less than 0.05). GH administration also
      resulted in increased total gastric DNA, RNA, and protein content but did not
      produce significant differences in DNA, RNA, or protein content when normalized
      to stomach wt. Morphometric analysis of the gastric mucosa revealed a
      significantly (P less than 0.05) increased gastric epithelial height and mucosal
      surface area along with an increase in the proportion of nuclei with multiple
      nucleoli (P less than 0.01). The number of gastric mucosal cells in S-phase was
      determined by immunohistochemical detection of nuclear 5'-bromo-2'-deoxyuridine
      (BrdU) incorporated during a 2 h pulse of BrdU. GH treatment resulted in a 74%
      increase (P less than 0.05) in the number of BrdU-labeled nuclei/mm2 mucosa
      relative to vehicle-injected control animals. A modification of Zimmerman's
      method for the differential staining of gastric mucosa was used to delineate cell
      type for morphometric analysis. This showed that the density of differentiated
      (parietal and chief) cell types was not significantly different between DW- and
      to DW+ animals. Soluble extracts of gastric mucosa were prepared for estimation
      of pepsinogen content and [57Co]cyanocobalamin (vitamin B12) binding. GH
      administration produced no significant change in pepsinogen content per mg
      protein and did not affect the relative levels of pepsinogen isoenzymes as
      determined by polyacrylamide gel electrophoresis. GH administration did however
      result in an 86% increase (P less than 0.01) in [57Co]cyanocobalamin binding per
      mg protein. The increase in binding was totally displaceable by 1 microgram/ml
      unlabeled cyanocobalamin but not by 1 microgram/ml cobinamide dicyanide
      indicating it was the result of increased intrinsic factor rather than R protein.
      Sephadex S-300 gel filtration of mucosal extracts revealed an elution profile for
      [57Co]cyanocobalamin identical to that of purified porcine intrinsic factor and
      different from that of human salivary R protein. In conclusion, we have
      demonstrated that GH stimulates proliferation and enlargement of the gastric
      mucosa without significant alteration in cellular composition.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1374020
TI  - Cellular localization of the growth hormone binding protein in the rat.
AB  - In the rat a GH-binding protein (GHBP) exists that is derived from the GH
      receptor gene by an alternative messenger RNA splicing mechanism such that the
      transmembrane and intracellular domains of the GH receptor are replaced by a
      hydrophilic carboxy terminus. Previous immunohistochemical studies detailing the
      localization of the GH receptor binding protein (BP) have used monoclonal
      antibodies that recognize extracellular region-specific epitopes common to both
      the GH receptor and GHBP. In this study we have used a monoclonal antibody (MAb
      4.3) specific for the carboxy terminus of the rat GHBP to map its somatic
      distribution in the rat and have compared this distribution with that of a MAb
      recognizing both the BP and the GH receptor. A variety of tissues including the
      skeletal and muscular systems, the gastrointestinal tract and derivatives, the
      male and female reproductive systems, skin, central and peripheral nervous
      systems, and the 18 day gestation fetus were investigated. The distribution of
      GHBP immunoreactivity (MAb 4.3) was widespread and identical to that previously
      reported for the extracellular region of the GH receptor (MAbs 263 and 43).
      Immunoreactivity was both cytoplasmic and nuclear, indicating a possible role for
      the GHBP in intracellular function. GHBP immunoreactivity was predominantly
      associated with epithelial/endothelial cell subtypes and with mesenchymal
      elements such as muscle, chondrocytes, and osteoblasts, as previously described
      for the GH receptor extracellular region. We also report here the distribution of
      the GH receptor/GHBP in the kidney, cardiovascular, and respiratory systems. The
      most prominent immunoreactivity (MAbs 4.3 and 263) was associated with the distal
      convoluted tubules and collecting ducts of the kidney, with the epithelium and
      smooth muscle of the broncho-alveolar tree (including type I and II pneumocytes),
      with the Purkinje and myocardial fibers of the heart and with the endothelium and
      smooth muscle of blood vessels. Thus we have identified sites of direct GH action
      in the cardiovascular, renal, and respiratory systems. In conclusion, the
      extensive cellular distribution of the GHBP in the rat indicates physiological
      function(s) other than the binding of GH in plasma. Since GHBP mRNA has also been
      reported in a number of tissues, it may be that the GHBP is synthesized locally
      to mediate intracellular transport of GH and/or transcriptional regulation by GH
      in a variety of target tissues.

PMID- 1374021
TI  - Rat ovarian insulin-like growth factor binding protein-3: a growth hormone
      dependent theca-interstitial cell-derived antigonadotropin.
AB  - To further the identification and characterization of insulin-like growth factor
      binding proteins at the level of the immature rat ovary, we have set out to study
      the ovarian expression, cellular localization, and hormonal regulation of the
      insulin-like growth factor binding protein (IGFBP)-3. To this end, use was made
      of a solution hybridization/RNAse protection assay wherein ovarian total RNA from
      immature (21-23 days old) female rats was hybridized with a 343 bases-long [32P]
      labeled rat IGFBP-3 riboprobe. As in liver, a single protected fragment (315
      bases-long) corresponding to IGFBP-3 transcripts was identified in whole ovarian
      material. Cellular localization studies revealed the IGFBP-3 gene to be
      exclusively expressed in the theca-interstitial rather than the granulosa cell
      compartment. To confirm presence and cellular distribution of the IGFBP-3
      protein, media conditioned by cultured granulosa cells, theca-interstitial cells,
      and whole ovarian dispersates were subjected to Western Ligand Blotting.
      Importantly, media conditioned by cultured theca-interstitial (but not granulosa)
      cells displayed an IGFBP the size of rat IGFBP-3 (46kDa) as determined by
      comigration with a rat serum standard. A similarly-sized band was apparent in
      media conditioned by cultured whole ovarian dispersates reflecting in all
      likelihood the contribution of the theca-interstitial cell component.
      Significantly, deglycosylation of media conditioned by cultured theca
      interstitial cells revealed the glycosylated nature of the 46kDa IGFBP species as
      judged by the apparent reduction in its molecular size to 35kDa. Similar
      alterations were noted in corresponding rat serum samples. Hypophysectomy of
      immature rats resulted in a modest but statistically insignificant decrease in
      the relative (densitometrically-quantified) abundance of ovarian IGFBP-3
      transcripts, an effect further augmented by the systemic provision of either FSH
      or diethylstilbestrol (DES). In contrast, systemic treatment of hypophysectomized
      rats with GH produced a marked (3.2-fold) increase (P less than 0.05) in the
      steady state levels of ovarian (as well as hepatic) IGFBP-3 transcripts. However,
      the concurrent provision of either FSH or DES resulted in substantial (P less
      than 0.05) attenuation (78 and 57% inhibition, respectively) of the upregulatory
      GH effect. These findings document the highly compartmentalized expression of the
      IGFBP-3 gene at the level of the immature rat ovary, implicate the theca
      interstitial cell as the sole source of its generation, reveal its pituitary
      dependence, and disclose its diametrically-opposed (indeed antagonistic)
      regulation by FSH (or estrogens) and GH.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374022
TI  - Partial characterization of the gonadotropin-releasing hormone (GnRH) gene
      transcript in the rat ovary.
AB  - It has been hypothesized that GnRH or a GnRH-like peptide is produced in the rat
      ovary, but the presence of GnRH in the ovary has not been unequivocally
      demonstrated. This study was undertaken to determine whether the GnRH gene is
      expressed in the rat ovary and to compare the GnRH gene transcripts from the
      ovary and the hypothalamus. Twelve samples of total RNA from ovaries of
      individual rats were screened by reverse transcription-polymerase chain reaction
      (RT-PCR) for the presence of GnRH gene transcripts. Fragments of GnRH cDNA were
      amplified using pairs of specific primers. GnRH transcripts were detected in all
      the ovaries examined, and differed from hypothalamic GnRH transcripts in two
      ways: first, in the ovaries a greater proportion of GnRH transcripts contained
      intronic sequences; second, the major transcription start utilized in the ovary
      differed from that used in the hypothalamus. Although fully processed GnRH gene
      transcripts were detected by RT-PCR in both, ovary and hypothalamus, they were
      not detected in the ovary by Northern blot. The GnRH probe hybridized
      specifically to the predicted 0.6 kb transcript in the hypothalamus, and to a 3.3
      kb transcript in the ovary. We conclude that in the ovary, most GnRH gene
      transcripts retain intronic sequences.

PMID- 1374023
TI  - Lung cytokine production in bleomycin-induced pulmonary fibrosis.
AB  - In bleomycin-induced pulmonary fibrosis, lung injury is accompanied with
      inflammation and subsequent fibrosis. In this study, lung mRNA for several
      cytokines was measured in bleomycin-treated mice to evaluate their roles in lung
      fibrosis. Significant increases in tumor necrosis factor-alpha (TNF-alpha) and
      transforming growth factor-beta (TGF-beta) mRNA were found in lungs of bleomycin
      treated responder CBA mice but not in nonresponder BALB/c mice. Increases in
      responder animals peaked on day 7 after bleomycin administration, and
      subsequently returned toward control levels. This time course paralleled that for
      the increase in beta-actin mRNA, but preceded the peak increase in mRNA for
      collagens I and III. When lung macrophages were analyzed for cytokine secretion,
      differences were observed between alveolar macrophages and interstitial cells,
      and between cells from bleomycin-responsive CBA and nonresponsive BALB/c mice.
      Only alveolar macrophages from CBA mice secreted increased amounts of IL-1. TNF
      alpha activity was increased in conditioned media of alveolar and interstitial
      cells of CBA mice, while only alveolar macrophages of nonresponder BALB/c mice
      secreted any activity. The kinetics of the increased secretion of TNF-alpha was
      dissimilar for these different cells. These results are consistent with the
      conclusion that increased production of TNF-alpha and TGF-beta is an important
      component of the fibrotic process.

PMID- 1374025
TI  - Interspecies cytogenetic comparisons: studies with X-radiation and bleomycin
      sulfate.
AB  - A series of in vitro experiments were conducted to determine if there are innate
      differences in the sensitivity of peripheral blood lymphocytes (PBLs) from
      different mammalian species to clastogens. Mouse, rat, and human whole blood
      samples were exposed to either 0, 0.38, 0.75, 1.5, or 3.0 Gy x-radiation or 0, 5,
      10, 20, 40, or 80 micrograms/ml bleomycin for 4 hr. Bromodeoxyuridine-containing
      cultures were initiated and the PBLs stimulated to divide with
      phytohemagglutinin. All cultures were harvested following a 3-hr colcemid
      treatment. Slides were made and differentially stained, and first-division
      metaphases were scored for chromosome aberrations. In the x-radiation studies
      human PBLs were significantly more sensitive than mouse PBLs which were in turn
      more sensitive than rat PBLs as measured by either the total percent aberrant
      cells or the number of dicentrics. Data from all three species could be fitted to
      a linear-quadratic model. Results with bleomycin suggest that the mouse and human
      PBLs are equally sensitive to the clastogenic effects of bleomycin. Both appeared
      to be more sensitive than the rat PBLs, but the variation between experiments was
      such that the results among species were not significantly different. These
      results indicate that there may be inherent differences in sensitivity among PBLs
      of mammalian species; however, more studies are needed to determine if the
      differences presented here hold for other agents.

PMID- 1374024
TI  - Prostaglandins PGE2 and PGF2 alpha in human fetal lung: immunohistochemistry and
      release from organ culture.
AB  - Immunohistochemical studies in human fetal lung have shown that epithelial and
      endothelial cells are both strongly and equally reactive for PGE2. In contrast,
      epithelial PGF2 alpha reactivity varied between fetuses, in some as intense as
      endothelial staining and in others very much less. As lung organ cultures
      differentiated, the intensity of PGE2 staining declined in airways and blood
      vessels, although it was still weakly positive at 10 days. In contrast,
      epithelial cells rapidly became negative for PGF2 alpha, whereas PGF2 alpha
      positivity was retained in blood vessels, albeit less obviously. PGF2 alpha and
      PGE2 were released into the media of organ cultures in decreasing amounts as
      cultures progressed. Amounts of released PGF2 alpha were greater by 2- to 10-fold
      than PGE2. Our findings suggest that the endogenous production of prostaglandins
      by human fetal lung in organ culture has a key role in the self-differentiation
      process that occurs in the absence of sera or added growth factors or hormones.

PMID- 1374026
TI  - Identification and characterization of the murine cell surface receptor for the
      urokinase-type plasminogen activator.
AB  - Cell-binding experiments have indicated that murine cells on their surface have
      specific binding sites for mouse urokinase-type plasminogen activator (u-PA). In
      contrast to the human system, chemical cross-linking studies with an iodinated
      ligand did not yield any covalent adducts in the murine system, but in ligand
      blotting analysis, two mouse u-PA-binding proteins could be visualized. To
      confirm that these proteins are the murine counterpart of the human u-PA receptor
      (u-PAR), a peptide was derived from the murine cDNA clone assigned to represent
      the murine u-PAR due to cross-hybridization and pronounced sequence similarity
      with human u-PAR cDNA [Kristensen, P., Eriksen, J., Blasi, F. & Dano, K. (1991)
      J. Cell Biol. 115, 1763-1771]. A rabbit antiserum raised against this peptide
      specifically recognized two polypeptide bands with electrophoretic mobilities
      identical to those identified by ligand-blotting analysis. Binding of mouse u-PA
      to its receptor showed species specificity in ligand-blotting analysis, since
      mouse u-PA did not bind to human u-PAR and human u-PA did not bind to mouse u
      PAR. The apparent M(r) of mouse u-PAR varied between different mouse cell lines
      and ranged over M(r) 45,000-60,000. In four of the cell lines, mouse u-PA bound
      to two mouse u-PAR variant proteins, whereas in the other two cell lines studied,
      there was only one mouse u-PA-binding protein. In the monocyte macrophage cell
      line P388D.1, trypsin-treatment of intact cells could remove only the large mouse
      u-PAR variant (M(r) 60,000) indicating that only this type was a cell-surface
      exposed molecule. The smaller mouse u-PAR variant (M(r) 45,000), was
      deglycosylated by the enzyme endo-beta-N-acetylglucosaminidase H and is probably
      an intracellular precursor form carrying only high-mannose carbohydrate.
      Deglycosylation of this variant yielded a polypeptide with an apparent M(r) of
      about 30,000, which corresponds to the Mr calculated from the cDNA derived
      protein sequence of mouse u-PAR. Receptor-bound mouse u-PA could be released by
      phosphatidylinositol-specific phospholipase C treatment, indicating that mouse u
      PAR is attached to the cell surface by glycosylphosphatidylinositol. Purification
      of the two mouse u-PAR variant proteins by diisopropylfluorophosphate-inactivated
      mouse u-PA-Sepharose affinity chromatography yielded two silver-stained bands
      when analysed by SDS/PAGE, corresponding in electrophoretic mobility to those
      seen by ligand-blotting analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374028
TI  - Structural studies on fetal mucins from human amniotic fluid. Core typing of
      short-chain O-linked glycans.
AB  - Mucins in human amniotic fluid are represented by two distinct molecular species,
      FM-1 and FM-2, with apparent molecular masses of 700 and 570 kDa, respectively,
      in SDS/polyacrylamide gradient gels. FM-1 and FM-2 were isolated by preparative
      SDS/PAGE to apparent homogeneity and subjected to structural studies on their
      carbohydrate portions. The carbohydrate compositions of the mucin species
      differed only marginally and exhibited significant amounts of mannose. O-linked
      core-region glycans on human amniotic mucin-derived pronase-stable glycopeptides
      were analyzed after reductive beta-elimination and purification on HPLC by a
      combination of methylation analysis, electron-impact mass spectrometry of
      permethylated oligosaccharide alditols and fast-atom-bombardment mass
      spectrometry of acetylated or methylated alditols (positive-ion mode) or alditol
      derived neoglycolipids (negative-ion TLC-MS). The primary structures of major
      monosaccharides to tetrasaccharides have been established which exhibit at their
      reducing termini core 1, core 2 and core 3 sequences, as follows. [Table; see
      text]

PMID- 1374027
TI  - Mutants of human insulin-like growth factor II (IGF II). Expression and
      characterization of truncated IGF II and of two naturally occurring variants.
AB  - Insulin-like growth factor II (IGF II) and four structural analogs, constructed
      by site-directed mutagenesis, were expressed as protein A fusion proteins in
      Escherichia coli BL21pLysS cells, cleaved with cyanogen bromide and purified by
      affinity chromatography and HPLC. Two mutants (Ser29 substituted by Arg-Leu-Pro
      Gly, and Ser33 substituted by Cys-Gly-Asp) represent two naturally occurring
      variants of IGF II. The other two mutants, (7-67)IGF II and (9-67)IGF II, are
      truncated at the amino-terminus in analogy to the naturally occurring des(1-3)IGF
      I ('truncated IGF I'). These mutants were tested for their binding affinities to
      type-1 and type-2 IGF receptors, to IGF binding protein-3 (IGFBP-3) and for their
      stimulation of thymidine incorporation into DNA. The affinities of the Ser29 and
      Ser33 mutants to the type-1 IGF receptor were 85% and 39%, respectively, compared
      to wild-type IGF II, those of (7-67)IGF II and (9-67)IGF II 96% and 15%,
      respectively. The potencies of the Ser33 and the (9-67) mutant to stimulate
      thymidine incorporation into DNA correlated closely with the affinities to the
      type-1 IGF receptor, whereas the bioavailability of the Ser29 mutant was lower
      and that of the (7-67) mutant higher than the type-1 receptor binding, possibly
      due to interferences with endogenously secreted IGFBPs. The affinities of the
      Ser29 and Ser33 mutants to the type-2 IGF receptor were 110% and 71%,
      respectively, those of the two truncated mutants 25% and 23%, respectively. The
      affinity of the Ser29 mutant to IGFBP-3 was increased to 171%, whereas those of
      the Ser33 mutant and the two truncated mutants were reduced (34%, 10% and 19%,
      respectively).

PMID- 1374029
TI  - A simple procedure for tenascin purification.
AB  - Here we describe a two-step procedure for purification of human tenascin from
      conditioned medium of the SK-MEL-28 human melanoma cell line. The first step
      consists in passing the conditioned media through two chromatography columns
      connected in sequence. The first is a large capacity gelatin--Sepharose affinity
      chromatography column (to remove fibronectin), the second, over which the unbound
      material from the first column flows directly, is a hydroxyapatite chromatography
      column. Under these conditions, all tenascin present in the conditioned medium
      binds to the hydroxyapatite chromatography column from which it is then eluted by
      a 5-300 mM sodium phosphate gradient. With this step, we obtain a crude tenascin
      preparation, concentrated about 20 times with respect to the starting conditioned
      medium, and in which tenascin represents more than 50% of the total protein. The
      second step consists of two sequential precipitations with 6% and 12.8%
      poly(ethylene glycol). After this step, tenascin is more than 95% pure and does
      not show any contamination of chondroitin-sulfate-containing proteoglycans that
      are known to bind to it. From 21 medium we obtain about 3-4 mg tenascin which
      corresponds to a yield of about 40-50%. This procedure gives a higher yield, is
      simpler with respect to procedures previously described, avoids the exposure of
      the protein to denaturing agents or harsh conditions and could be used for
      purification of tenascin from the conditioned media of other cell lines. Thus,
      this procedure may represent a simple and useful tool for the preparation of
      tenascin to study its biological functions.

PMID- 1374030
TI  - Comparison of human tenascin expression in normal, simian-virus-40-transformed
      and tumor-derived cell lines.
AB  - Tenascin is a polymorphic high-molecular-mass extracellular-matrix glycoprotein
      composed of six similar subunits. Using two-domain-specific anti-tenascin
      monoclonal antibodies, we have studied the expression and distribution of
      tenascin in four cultured normal human fibroblasts, two simian-virus-40-(SV40)
      transformed and three tumor-derived (melanoma, rhabdomyosarcoma and fibrosarcoma)
      cell lines. We found that (a) cultured normal human fibroblasts accumulate
      considerable amounts of tenascin and retain 60-90% in the extracellular matrix,
      while they release the remainder into the tissue-culture medium; (b) of the two
      SV40-transformed counterparts we have tested, the AG-280 cell line accumulates no
      detectable amounts of tenascin and the WI-38-VA cell line accumulates about 10
      times less tenascin than its normal counterpart and releases about 90% of it into
      the culture medium; (c) some tumor-derived cell lines accumulate considerable
      amounts of tenascin, but in these cases, more than 90% is released into the
      culture media; (d) in normal human fibroblasts, two major tenascin isoforms,
      generated by alternative splicing of the mRNA precursor, are detectable (280 kDa
      and 190 kDa, respectively) and the lower-molecular-mass tenascin isoform is
      accumulated preferentially in the extracellular matrix; (e) in SV40-transformed
      or tumor-derived cell lines, only the higher-molecular-mass isoform is detectable
      and it is more sialylated than the tenascin produced by the normal human
      fibroblast cell lines.

PMID- 1374031
TI  - The carbohydrate chains of the beta subunit of human chorionic gonadotropin
      produced by the choriocarcinoma cell line BeWo. Novel O-linked and novel
      bisecting-GlcNAc-containing N-linked carbohydrates.
AB  - The N-linked carbohydrate chains of the beta subunit of human chorionic
      gonadotropin (hCG-beta) isolated from the culture fluid of the choriocarcinoma
      cell line BeWo were released enzymatically by peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase F. Subsequently, the O-linked oligosaccharides
      were split off from the N-deglycosylated protein by mild alkaline borohydride
      treatment. The carbohydrate chains were purified in their intact sialylated forms
      by FPLC anion-exchange chromatography on Mono Q, HPLC on Lichrosorb-NH2, and high
      pH anion-exchange chromatography on CarboPac PA1. 1H-NMR spectroscopic analysis
      of the major fractions demonstrates the occurrence of the following sialylated
      diantennary and triantennary N-linked oligosaccharides. Residues not written in
      bold letters are variably present. [formula: see text] The incidence of
      triantennary carbohydrate chains is much higher than in normal urinary hCG-beta
      (26% vs 2%). The same holds for the alpha 1-6-fucosylation of the asparagine
      bound GlcNAc (95% vs 42%). The presence of a bisecting GlcNAc and the occurrence
      of alpha 2-6-linked Neu5Ac in the most abundant N-glycans, are new features for
      hCG-beta. The major O-linked carbohydrate chains identified are the
      tetrasaccharide Neu5Ac alpha 2-3Gal beta 1-3(Neu5Ac alpha 2-6)GalNAc-ol and the
      hexasaccharide Neu5Ac alpha 2-3Gal beta 1-4GlcNAc beta 1-6(Neu5Ac alpha 2-3Gal
      beta 1-3)GalNAc-ol, both also found in normal urinary hCG. In addition, two novel
      O-glycans were characterized: [formula: see text]

PMID- 1374032
TI  - Apparent lack of N-glycosylation in the asexual intraerythrocytic stage of
      Plasmodium falciparum.
AB  - This study investigates protein glycosylation in the asexual intraerythrocytic
      stage of the malaria parasite, Plasmodium falciparum, and the presence in the
      infected erythrocyte of the respective precursors. In in vitro cultures, P.
      falciparum can be metabolically labeled with radioactive sugars, and its
      multiplication can be affected by glycosylation inhibitors, suggesting the
      capability of the parasite to perform protein-glycosylation reactions. Gel
      filtration analysis of sugar-labeled malarial proteins before and after specific
      cleavage of N-glycans or O-glycans, respectively, revealed the majority of the
      protein-bound sugar label to be incorporated into O-glycans, but only little (7
      12% of the glucosamine label) or no N-glycans were found. Analysis of the
      nucleotide sugar and sugar-phosphate fraction showed that radioactive galactose,
      glucosamine, fucose and ethanolamine were converted to their activated
      derivatives required for incorporation into protein. Mannose was mainly recovered
      as a bisphosphate, whereas the level of radiolabeled GDP-mannose was below the
      detection limit. The analysis of organic-solvent extracts of sugar-labeled
      cultures showed no evidence for the formation by the parasite of dolichol cycle
      intermediates, the dedicated precursors in protein N-glycosylation. Consistently,
      the amount of UDP-N-acetylglucosamine formed did not seem to be affected by the
      presence of tunicamycin in the culture. Oligosaccharyl-transferase activity was
      not detectable in a lysate of P. falciparum, using exogenous glycosyl donors and
      acceptors. Our studies show that O-glycosylation is the major form of protein
      glycosylation in intraerythrocytic P. falciparum, whereas there is little or no
      protein N-glycosylation. A part of these studies has been published in abstract
      form [Dieckmann-Schuppert, A., Hensel, J. and Schwarz, R. T. (1991) Biol. Chem.
      Hoppe-Seyler 372, 645].

PMID- 1374033
TI  - Different immunologic properties of the globular NC1 domain of collagen type IV
      isolated from various human basement membranes.
AB  - The C-terminal globular domain NC1 of collagen IV, which carries the epitopes
      recognized by anti-GBM antibodies in Goodpasture's syndrome, was isolated from
      human basement membranes (BM) of glomeruli (GBM-NC1), tubules (TBM-NC1), lung
      (ABM-NC1), placenta (PBM-NC1), and small intestine (IBM-NC1). All NC1 hexamers
      were of globular size on electron microscopy. On SDS-PAGE, the hexamers
      dissociated into monomeric and dimer-sized subunits of similar molecular weights.
      The following monomer:dimer relationships were identified: GBM-NC1, and PBM-NC1 =
      1:3; ABM-NC1 = 1:4; and IBM-NC1 = 1:32. On immunoblot, all dimers of the various
      NC1 globules showed binding of anti-GBM antibodies. However, monomers stained
      differently, with three monomers demonstrable in GBM-NC1 and no monomer staining
      in PBM-NC1. In addition, studies with monoclonal antibodies showed that the C
      terminus of the alpha 1(IV) collagen chain was demonstrable in all different NC1
      hexamers. In contrast, the alpha 3(IV) chain, to which Goodpasture sera
      preferentially bind, showed a restricted distribution. One monomer and dimers
      were demonstrable in GBM-NC1 and ABM-NC1, only a weak dimer staining was seen in
      TBM-NC1, while no evidence for alpha 3(IV) was found in IBM-NC1 and PBM-NC1.
      Dissociation by 6 M guanidine-HC1 or treatment by acid increases the apparent
      number of accessible epitopes for anti-GBM antibodies. In addition, dose-response
      curves, which were obtained by incubation of increasing concentrations of NC1
      with anti-GBM antibody positive sera, indicated that for GBM-NC1 and ABM-NC1 the
      lowest NC1 protein concentrations were necessary to bind 50% of the
      antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374034
TI  - Cytokeratin reorganization induced by adenosine diphosphate in kidney epithelial
      cells.
AB  - Exogenous adenosine diphosphate (ADP), the most potent mitogen for nontransformed
      African green monkey kidney epithelial cells of the BSC-1 line, rapidly alters
      the appearance of the cell monolayer. Examination of the cells with indirect
      immunofluorescence using monoclonal antibodies reveals a considerable
      reorganization of cytokeratin filaments without a major change in the pattern of
      microtubules or microfilaments. In untreated confluent cells, cytokeratin
      filaments are predominantly confined to a star-like spot in the perinuclear area,
      but these can be seen to begin to spread within 2 min after addition of ADP. The
      effect is particularly notable using anti-cytokeratin 8 antibodies. At 6 h this
      process is complete and produces a well-developed filamentous network throughout
      the cell. By 12 h, the network appears to collapse, so that the filaments again
      form a spot in the perinuclear area, a process that is complete by 24 h.
      Immunoblotting of total cellular proteins reveals no apparent alterations in the
      amounts of several species of cytokeratins, including cytokeratin 8 and 18, at 3
      or 24 h after exposure to ADP. Other purine and pyrimidine nucleotides which do
      not stimulate DNA synthesis in these cells fail to alter cytokeratin
      organization, and there is no apparent alteration in the distribution of
      vimentin, another intermediate filament protein. The rapid ADP-induced
      cytokeratin reorganization appears to coincide with the induction of early growth
      response gene transcription in these cells and may be correlated with the
      capacity of ADP to subsequently initiate DNA synthesis. This dramatic and
      reversible cytokeratin reorganization immediately after exposure to ADP may be an
      important step in the mitogenic signal transduction pathway.

PMID- 1374035
TI  - Introduction of large molecules into viable fibroblasts by electroporation:
      optimization of loading and identification of labeled cellular compartments.
AB  - Access to the cell cytoplasm in viable cells may permit direct labeling or
      manipulation of intracellular molecules and metabolic processes. One method to
      gain access to the cell cytoplasm is by electroporation, a technique that
      transiently creates pores in cell membranes by means of applied electrical
      fields. We used electroporation to introduce large-molecular-mass dextrans and
      proteins as probes of the cytoplasmic compartment in human gingival fibroblasts.
      Electrical field strength and pulse decay time were optimized to obtain cellular
      viability greater than 80%. Analysis by confocal microscopy and by fluorescence
      spectrophotometry demonstrated that a large proportion of high-molecular-mass
      probe was membrane-bound after electroporation. Trypsinization did not affect
      membrane-bound FITC-dextran but eliminated protein probe incorporated into the
      membrane, thereby permitting measurement of only intracellular, cytoplasmic
      label. Proteins of up to 66 kDa were incorporated at intracellular concentrations
      of 10(-15) M. After electroporation under optimal conditions, incorporated anti
      vimentin antibodies were capable of binding to vimentin. Cells electroporated in
      the presence of RNase A exhibited significant reductions of cellular RNA.
      Electroporation appears to be a useful approach to probe or perturb specific
      cellular processes by introduction of functional molecular species into the
      cytoplasm of viable cells.

PMID- 1374036
TI  - Beta 1 and beta 3 integrins have different roles in the adhesion and migration of
      vascular smooth muscle cells on extracellular matrix.
AB  - Extracellular matrix receptors on ductus arteriosus smooth muscle cells (SMC)
      must enable the cells to migrate through both interstitial and basement membrane
      matrices to form intimal mounds during postnatal ductus closure. We examined the
      role of beta 1 and beta 3 integrin receptors on SMC adhesion and migration. Using
      a new assay to measure cell migration, we found that lamb ductus arteriosus SMC
      attach to and migrate over surfaces coated with fibronectin (FN), laminin (LN),
      vitronectin (VN), and collagens I (I) and IV (IV). Blocking antibodies, specific
      to different integrin complexes, showed that SMC adhesion to FN, LN, I, and IV
      depended exclusively on functioning beta 1 integrins with little, if any,
      contribution by the alpha V beta 3 integrin; on the other hand, cell migration
      over these substrates depended to a large extent on the alpha V beta 3 receptor.
      Immunofluorescent staining demonstrated that during the early phase of SMC
      migration, the beta 1 integrins organized rapidly into focal plaques that, with
      time, gradually covered the cell's basal surface; on the other hand, the beta 3
      receptor remained concentrated at all times at the cell's margins. Ligand
      affinity chromatography and immunoprecipitation techniques identified a unique
      series of beta 1 integrins binding to each matrix component: FN (alpha 5 beta 1,
      alpha 3 beta 1, alpha V beta 1), LN (alpha 1 beta 1, alpha 7 beta 1), VN (alpha V
      beta 1), I (alpha 1 beta 1, alpha 2 beta 1), and IV (alpha 1 beta 1). In
      contrast, the beta 3 integrin, alpha V beta 3, bound to all the substrates
      tested: FN, LN, VN, I, and IV. The results indicate that beta 1 and beta 3
      integrins may play different roles in attachment and migration as SMC move
      through the vascular extracellular matrix to produce obliteration of the ductus
      arteriosus lumen.

PMID- 1374037
TI  - The ret oncogene can induce melanogenesis and melanocyte development in Wv/Wv
      mice.
AB  - We recently reported the establishment of transgenic mouse lines carrying the
      mouse metallothionein/ret fusion gene in which severe melanosis and melanocytic
      tumors developed. In the present study, we demonstrate that a significant number
      of pigmented hairs developed in Wv/Wv mice crossed to one of the transgenic mouse
      lines. The pigmented hair of Wv/Wv mice carrying the ret oncogene did not lose
      color during aging and reappeared after shaving, indicating that the melanocytes
      in the hair follicle function. The melanocytic tumors also developed in these
      mice, although the incidence was lower than that in the wild transgenic mice.
      Furthermore, the neutral tube culture of mouse embryos indicated that neural
      crest cells of the transgenic mice gave rise to a cell population that
      autonomously produced melanin even in the absence of melanocyte stimulating
      hormone. These results strongly suggested that the introduced ret oncogene could
      compensate for the defect of c-kit in Wv mice during both embryogenesis and
      postnatal life and induce a high level of melanin synthesis in the process of
      melanocyte development.

PMID- 1374039
TI  - Blastomycosis in Africa: a new case from Tunisia.
AB  - Although blastomycosis is prevalent in the North American continent, it occurs
      only sporadically in Africa. We describe a 42 yr old patient who complained of
      intermittent cough and haemoptysis. Clinical findings were strongly suggestive of
      lung cancer. The diagnosis of pulmonary blastomycosis was made at thoracotomy.
      This rather unusual disease in our areas caused a considerable delay in securing
      the diagnosis and we suggest that this infection may be found elsewhere in Africa
      and the distribution may be wider than has previously been suspected.

PMID- 1374038
TI  - Role of the glycosylphosphatidylinositol/inositol phosphoglycan system in human
      fibroblast proliferation.
AB  - The involvement of the glycosylphosphatidylinositol/inositol phosphoglycan (gly
      PtdIns/IPG) system in the stimulation of macromolecular syntheses in human
      fibroblasts has been investigated. The study demonstrates that an insulin
      sensitive gly-PtdIns/IPG system is present in human fibroblasts, that IPG can
      significantly stimulate DNA, RNA, and protein synthesis, and that the action of
      insulin on DNA synthesis as well as that of IPG can be significantly reduced by a
      specific anti-IPG antibody. These results strongly support the hypothesis that
      the gly-PtdIns/IPG system is involved in the signal transduction pathway leading
      to the stimulation of cell proliferation.

PMID- 1374041
TI  - Metabolic activity in inflammatory and non-inflammatory aneurysms of the
      abdominal aorta.
AB  - Inflammatory aneurysms of the abdominal aorta (IAA) comprise 10-15% of all aortic
      aneurysms (AA) but their aetiology and pathogenesis are obscure. Destruction of
      mural elastin is a prominent feature of IAA, and both increased elastolysis and
      decreased inhibition of elastolysis have been implicated. In order to study these
      factors, we have examined the peripheral blood of three groups of patients; 15
      with inflammatory aortic aneurysms (IAA), 61 with simple aortic aneurysms (SAA)
      and 35 with aorto-iliac occlusive disease (OD). In all cases, alpha-1-anti
      trypsin (A-1-AT), alpha-2-macroglobulin (A-2-MG), elastase inhibitory activity
      (E.I.A.), elastase-anti-trypsin complex, C-reactive protein (CRP), caeruloplasmin
      (CP) and plasma viscosity were measured. Patients with IAA had a significantly
      higher plasma viscosity (Mann-Whitney, p less than 0.05), E.I.A. (Mann-Whitney, p
      less than 0.01) and levels of A-1-AT, CRP, CP and elastase/anti-trypsin complex
      (Mann-Whitney, all p less than 0.05) than patients in the other two groups. There
      was no difference in the levels of A-2-MG between any of the groups. This study
      refutes the theory that reduced inhibition of elastase activity predisposes to
      the formation of SAA. In patients with IAA, raised marker levels indicate ongoing
      destruction of elastin, and suggest a difference in pathogenesis between IAA and
      SAA. The study also suggests that IAA are highly active metabolically, as opposed
      to the more degenerative SAA.

PMID- 1374040
TI  - Iloprost reduces peripheral resistance during femoro-distal reconstruction.
AB  - A randomised placebo-controlled trial was conducted to investigate the effect of
      iloprost, a stable prostacyclin mimetic, on peripheral resistance during femoro
      distal bypass. Patients undergoing femoro-distal long saphenous vein bypass for
      critical ischaemia received 3000 ng of iloprost or placebo infused into the graft
      via an unligated side branch over 2 min. Graft blood flow and peripheral
      resistance were measured for 20 min, using an operative Doppler flowmeter (OpDop
      130, SciMed, U.K.) and a pressure transducer to record graft pressure.
      Postoperatively, graft blood flow was assessed by daily duplex ultrasound for 7
      days. Iloprost produced an immediate drop in peripheral resistance in all cases
      (n = 18) by a mean (range) of 40% (4-80%) compared with controls (n = 15) in whom
      there was a 5.3% (-8 to +36%) increase in resistance (p less than 0.01, Wilcoxon
      test). Decreased peripheral resistance in iloprost-treated patients persisted to
      20 min. The largest decreases in peripheral resistance occurred in patients with
      the highest initial resistances (r = 0.56, p less than 0.02). Graft flow during
      the same period increased by 52% (-7 to 294%) compared with controls in whom
      there was a 6% (-17 to 26%) increase in flow, (p less than 0.01). Flow remained
      elevated by 53% over baseline values at 1 week post-infusion in the iloprost
      treated group but this did not achieve statistical significance compared to
      controls in whom flow also increased by 13%. Iloprost produces an immediate
      decrease in peripheral resistance associated with a prolonged increase in graft
      blood flow. This may reduce graft failure in the early postoperative period.

PMID- 1374042
TI  - Operative laparoscopy for the treatment of ovarian remnant syndrome.
AB  - OBJECTIVE: To present the technique and assess the efficacy of operative
      laparoscopy to manage ovarian remnant syndrome. DESIGN: Observational with a
      follow-up of 6 to 32 months. SETTING: Private subspecialty practice with a large
      referral base. PATIENTS: Thirteen women, 9 with previous bilateral salpingo
      oophorectomy and 4 with previous unilateral salpingo-oophorectomy and pain on the
      ipsilateral side. INTERVENTIONS: Multipuncture advanced operative laparoscopy.
      MAIN OUTCOME MEASURES: Patient pain relief was assessed through return
      examinations, telephone interviews, or contact with referring physicians.
      RESULTS: Nine patients reported complete pain relief. One reported incomplete but
      satisfactory pain relief. Two required bowel resection by laparotomy to obtain
      pain relief, and one, despite subsequent laparotomy, had persistent pain. No
      intraoperative or postoperative complications were noted. CONCLUSION: Laparoscopy
      can be effective in managing ovarian remnant syndrome when performed by an
      experienced laparoscopist.

PMID- 1374043
TI  - CD8+ lymphocyte subsets in human follicular fluid.

PMID- 1374044
TI  - Immunohistochemical detection of type I, III, and IV collagen in endometriosis
      implants.
AB  - OBJECTIVE: To determine if types I, III, or IV collagen are present in ectopic
      endometrium and to determine which type(s) of collagen are present in the
      connective tissue surrounding ectopic endometrial implants. DESIGN: Paired
      intrauterine and ectopic endometrial samples were obtained for study at the time
      of laparoscopy from women in the proliferative and secretory phase of the
      menstrual cycle. Connective tissue surrounding each ectopic implant was also
      obtained for study. SETTING: Academic research environment with institutional
      review board approval. PATIENTS: Six patients without endometriosis were used as
      controls. Ten additional patients with stage II or III endometriosis were
      studied. Only women on no medications participated in the study. MAIN OUTCOME
      MEASURES: Immunohistochemical techniques were used to identify the presence of
      collagen in biopsied specimens. RESULTS: Each collagen type studied was
      identified in the intrauterine endometrium of patients with and without
      endometriosis. All collagen types were also identified in each of the ectopic
      endometrial implants studied. The distribution of collagen in ectopic endometrial
      implants was similar to the distribution of collagen seen in intrauterine
      endometrium obtained from patients with or without endometriosis. Collagenous
      tissue that contained type I collagen was identified at the periphery of deep
      ectopic implants. CONCLUSIONS: This study demonstrates the presence of type I,
      III, and IV collagen in the intrauterine and ectopic endometrium of patients with
      endometriosis. Type I collagen was the predominant collagen present in the
      surrounding collagenous tissue associated with deep, ectopic endometrial
      implants.

PMID- 1374046
TI  - Isolation and expression of a murine purine nucleoside phosphorylase-encoding
      cDNA and sequence similarity with the human message.
AB  - To isolate murine purine nucleoside phosphorylase-encoding cDNA sequences (PNP),
      a murine BALB/c liver cDNA library in lambda gt10 was screened for recombinants
      hybridizing to a human PNP cDNA probe. Two of three clones recovered included
      inserts large enough to contain the full-length coding sequence. Sequence
      analysis of the largest clone revealed an 867-nucleotide open reading frame
      encoding 289 amino acids with 84% residue identity to that encoded by human PNP
      and 351 bp of 3'-untranslated region. The 5' end of the murine PNP message was
      specifically amplified by PCR using the RACE (rapid amplification of cDNA ends)
      protocol, revealing a 5'-untranslated region of 78 bp. Northern hybridization
      using the murine PNP cDNA sequence as a probe identified a message of approx. 1.6
      kb in mouse NIH3T3 cells which was slightly smaller than the human message
      observed in HeLa cells. The cloned murine PNP cDNA coding sequence was inserted
      into a mammalian expression vector under transcriptional regulation of the
      Moloney murine leukemia virus long terminal repeat. Transfection of this plasmid
      into human 293 cells resulted in the expression of PNP activity which co-focused
      with murine PNP activity extracted from NIH3T3 cells, verifying that the isolated
      murine PNP cDNA clone encoded catalytically active PNP protein.

PMID- 1374045
TI  - Characterization of human purified epithelial and stromal cells from endometrium
      and endometriosis in tissue culture.
AB  - OBJECTIVE: To initiate in vitro cultures of separate stromal and epithelial
      elements from endometriotic tissue and to compare the characteristics of these
      cells with those of cultured endometrial cells. DESIGN: The study involved
      testing the viability of a culture system for endometriotic tissue and
      examination of the phenotype of the cells. SETTING: Fresh tissue samples were
      collected from the operating theater and transferred to the tissue culture
      laboratory. PATIENTS, PARTICIPANTS: Twenty patients undergoing laparotomy for
      endometriosis and patients undergoing surgery for benign conditions were
      recruited. INTERVENTIONS: Endometrium and endometriotic tissue were separated,
      cultured in vitro, and labeled by indirect immunofluorescence with monoclonal
      antibodies against cytoskeletal components and epithelial mucins. MAIN OUTCOME
      MEASURES: Endometriotic cells have been maintained in vitro and found to resemble
      endometrial cells closely. RESULTS: With respect to the staining patterns for
      cytokeratins 18 and 19, vimentin, and three different epithelial mucins, cultured
      cells from both endometrium and endometriotic tissue had similar properties.
      Cytokeratins were located in epithelial cells, and vimentin was expressed in both
      stromal and epithelial cells. The antimucin antibodies all gave distinct patterns
      of intracellular staining of epithelial cells. CONCLUSIONS: Our results indicate
      a close similarity between cultured stromal and epithelial cells from endometrium
      and endometriotic deposits. Culture of these cell populations will permit study
      of their properties and interactions and may provide some insight into the cause
      of endometriosis.

PMID- 1374048
TI  - [Early developmental aspects of Tourette syndrome].
AB  - Tourette syndrome is a neuropsychiatric disorder characterized by a combination
      of multiple motor and vocal tics. It is frequently associated with other
      manifestations which are typical, though not obligatory for the diagnosis. Some
      of these manifestations may appear in early childhood and cause developmental
      disorders. Our observations in 2 families, in which an early developmental
      symptom was later found to be an associated manifestation of Tourette syndrome,
      led us to investigate our other patients with this syndrome. In all, 16 patients
      were studied. Early developmental disabilities, such as speech and language
      disorder, learning disabilities, attention deficit hyperactivity disorder, motor
      clumsiness or behavioral problems were found in 8. An epidemiological survey is
      needed to determine the prevalence of the association of Tourette syndrome with
      developmental manifestations in early childhood.

PMID- 1374047
TI  - High-level synthesis in Escherichia coli of shortened and full-length human
      acidic fibroblast growth factor and purification in a form stable in aqueous
      solutions.
AB  - A highly efficient expression for human acidic fibroblast growth factor (aFGF)
      has been assembled to direct the synthesis of both shortened and native full
      length aFGF. The full-length aFGF-154 form of the protein had not been produced
      before in Escherichia coli by genetic engineering, and is obtained with its
      initiator methionine removed. The high production of the aFGF allows one to
      circumvent the use of reversed-phase chromatography (RPC) during the purification
      procedure. Here, it is shown that RPC, routinely used to obtain pure preparations
      of recombinant aFGF, modifies its chemical and physical properties in an
      unfavorable manner.

PMID- 1374049
TI  - Comparative effect of porcine and rat galanin on growth hormone secretion in
      normal adult men.

PMID- 1374050
TI  - Videos focusing on teenage mothers, child sexual abuse, and poverty.

PMID- 1374051
TI  - Structure of the gene encoding CD34, a human hematopoietic stem cell antigen.
AB  - CD34 is a cell surface antigen of unknown function expressed in humans in
      hematopoietic stem cells, vascular endothelium, and blasts from 30% of patients
      with acute myeloid and lymphocytic leukemia. To begin to investigate the cis
      acting elements required for this tissue-specific expression, the human CD34
      locus was isolated and its genomic structure and transcriptional start site were
      characterized. The human CD34 gene spans 26 kb and has 8 exons, a structure quite
      similar to that of the murine gene. The start site of CD34 transcription was
      determined to be 258 bp upstream of the translational start site using RNase
      protection. These experiments also indicated that the 5' untranslated region has
      extensive secondary structure. In addition, fluorescence in situ hybridization
      was used to map the CD34 locus to band 1q32.

PMID- 1374052
TI  - Identification of a frameshift mutation (557 del T) in exon 4 of the CFTR gene.

PMID- 1374054
TI  - Production of granulocyte colony-stimulating factor at the materno-foetal
      interface in human pregnancy.
AB  - A bioassay specific for human granulocyte colony-stimulating factor (G-CSF) was
      developed and used to measure G-CSF production in human pregnancy tissues. G-CSF
      was secreted by both foetal chorionic villous and maternal decidual tissues taken
      in the first trimester and at term. The level of G-CSF production by placental
      tissue was 6750 (1250-10,000) units of bioactivity per g of tissue in 48 hr in
      the first trimester and 104 (83-190) U/g at term. Bioactive G-CSF was also
      secreted by decidual tissue, more in the first trimester than at term. ELISA
      immunoassays measured 75 (10-820) ng/g/48 hr of G-CSF antigen from first
      trimester placenta, 15 (10-50) ng/g from first trimester decidua and less than 2
      ng/g from term placenta. RNA isolated from decidual and chorionic villous tissue
      or from cells purified by flow cytometry, contained G-CSF mRNA in both tissues.
      In decidua, mRNA for G-CSF was confined to the macrophages, and cytotrophoblast
      from term amniochorion contained no detectable G-CSF mRNA. No G-CSF, measured as
      bioactivity or as mRNA, was detectable in choriocarcinoma cell lines.

PMID- 1374053
TI  - CD4+ T cells are required for antigen-specific recruitment of neutrophils by BCG
      immune spleen cells.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG)-immune spleen cells co
      inoculated into the peritoneal cavity of normal mice with BCG sonicate protein as
      antigen could induce an antigen-specific recruitment of neutrophils, dependent on
      the antigen dose and cell number. This response was significantly reduced by anti
      T lymphocyte and anti-CD4 treatment of the immune spleen cells prior to the
      inoculation. Removal of adherent or phagocytic cells or lysis of B cells, had no
      significant effect. Killing of dividing cells in the splenic population induced a
      slight reduction in the ability of spleen cells to recruit neutrophils. M. avium
      sonicate protein was also able to induce BCG-immune spleen cells to mobilize
      neutrophils but bovine serum albumin, Listeria monocytogenes cytosolic protein
      and 65,000 MW heat shock protein were not. These results show that CD4+ T cells
      are able to induce neutrophil recruitment in an antigen-specific way during a
      mycobacterial infection.

PMID- 1374055
TI  - Effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on
      murine resistance against Listeria monocytogenes.
AB  - Recombinant human granulocyte colony-stimulating factor (rh G-CSF) enhanced
      resistance of mice against Listeria monocytogenes (LM) as determined by survival
      and bacterial growth. Mice pretreated with rh G-CSF twice daily for 5 days
      survived better than untreated animals to the challenge with LM. Number of
      bacteria in peritoneal cavity (PC) and spleen was lower in treated mice than that
      in the control group. Rh G-CSF increased mainly polymorphonuclear cells (PMN) in
      blood and spleen. After LM inoculation, a larger number of PMN and monocyte
      macrophages accumulated in PC and spleen of tested mice. In addition, PMN primed
      in vivo with rh G-CSF released more superoxide anions when stimulated with
      phorbol myristate acetate. The inhibition of bacterial growth in PC and spleen
      could be ascribed to the accumulation of phagocytic cells at the infection sites
      and the increased oxidative metabolism. The results provided further evidence of
      the important contribution of G-CSF and neutrophils, as target cells, to the host
      defence against the intracellular bacteria.

PMID- 1374056
TI  - Involvement of antigen-presenting cells in the enhancement of the in vitro
      antibody responses by cholera toxin B subunit.
AB  - The enhancing effect of cholera toxin B subunit (CTB) on primary antibody
      responses to keyhole limpet haemocyanin (KLH) and the cellular basis of the
      effect were investigated, using in vitro cultures of mouse spleen cells. CTB (1
      100 ng/ml) enhanced anti-KLH IgM, IgG and IgA antibody responses in a dose
      dependent manner, when added to the cultures with KLH. This immunoenhancement was
      antigen specific, but not due to either polyclonal activation of the spleen cells
      or antigenic cross-reactivity between CTB and KLH. CTB did not affect the
      kinetics of the anti-KLH antibody responses. Early (Days 0-1) addition of CTB to
      the cultures enhanced the anti-KLH antibody production, whereas late (Days 5-7)
      addition of CTB did not. Addition of CTB with KLH to splenic adherent cells (SAC)
      resulted in a dose-dependent enhancement of the anti-KLH antibody responses, when
      the SAC were reconstituted with unimmunized non-adherent cells. Moreover, CTB
      enhanced IL-1 secretion from SAC incubated with KLH. These results suggest that
      CTB enhances the primary anti-KLH antibody responses in vitro by acting on early
      events in the responses, and that antigen-presenting cells play a major role in
      the enhancement.

PMID- 1374057
TI  - Membrane attack complex (MAC)-mediated damage to spermatozoa: protection of the
      cells by the presence on their membranes of MAC inhibitory proteins.
AB  - Although antibody and complement are known to cause immobilization and killing of
      spermatozoa in vitro the components of the complement system mediating these
      effects remain undefined. Here we have examined the effects of the membrane
      attack complex (MAC) on spermatozoa and demonstrate that spermatotoxic effects
      are dependent on assembly of the complete MAC. We subsequently examined the
      presence and functional significance of the complement regulatory proteins decay
      accelerating factor (DAF), MAC-inhibiting protein (MIP) and CD59 antigen on
      spermatozoa. Both DAF and CD59 antigen were present on the membranes of these
      cells. Neutralization of CD59 antigen with specific antibodies increased the
      susceptibility of the cells to MAC-mediated damage, suggesting a role for this
      molecule in the protection of spermatozoa from complement-mediated damage in the
      female reproductive tract.

PMID- 1374059
TI  - KY nailing of impending and pathological fractures of the proximal femur.
AB  - Eight two patients underwent 86 Kuntscher Y nailing for impending and
      pathological fractures of the proximal femur. All but five mobilised post
      operatively, thus improving their quality of life. Eighteen patients died in
      hospital. Prophylactic nailing improved survival. Fifteen out of 86 nailings were
      followed by complications.

PMID- 1374058
TI  - New monoclonal antibodies in CD59: use for the analysis of peripheral blood cells
      from paroxysmal nocturnal haemoglobinuria (PNH) patients and for the quantitation
      of CD59 on normal and decay accelerating factor (DAF)-deficient erythrocytes.
AB  - CD59 is a widely expressed cell surface glycosylphosphatidylinositol (GPI)-linked
      glycoprotein which acts as an inhibitor of the assembly of the membrane attack
      complex of autologous complement. Four new monoclonal antibodies to CD59 (2/24,
      1B2, BRIC 229, BRIC 257) are described. Competitive binding experiments using
      these antibodies, two known CD59 antibodies (MEM-43, YTH 53.1) and a previously
      described antibody LICR-LON-Fib75.1 demonstrated that all seven antibodies see
      related epitopes on human erythrocyte CD59. In common with other GPI-linked
      proteins, CD59 (as defined by antibody 2/24) was sensitive to treatment with
      phosphatidylinositol-specific phospholipase C (PI-PLC) on lymphocytes and
      monocytes but not on erythrocytes. Flow cytometric analysis using antibody 2/24
      identified two populations (CD59 positive and CD59 deficient) of lymphocytes,
      monocytes and erythrocytes in peripheral blood from a patient with paroxysmal
      nocturnal haemoglobinuria (PNH). The abundance of CD59 on normal erythrocytes was
      determined as 21,000 copies/cell when radioiodinated BRIC 229 was used. Other
      CD59 antibodies gave values of 10,000 (IF5) and 15,000 (2/24) against the same
      target cells. Radioiodinated Fab fragments of BRIC 229 gave a value of 39,000
      copies/cell. Erythrocytes from two individuals with a rare inherited deficiency
      of decay accelerating factor (DAF), known as the Inab phenotype, expressed normal
      levels of CD59.

PMID- 1374060
TI  - The results of radiotherapy for isolated elevation of serum PSA levels following
      radical prostatectomy.
AB  - Eleven patients were initially treated for localized prostate cancer with radical
      retropubic prostatectomy following negative pelvic lymph node dissection. Six or
      more months after surgery, these patients had elevated serum prostate specific
      antigen (PSA) levels. No patient had other clinical evidence of disease as
      determined by history, physical examination, bone scan, computed tomographic scan
      of the abdomen and pelvis, chest radiograph, complete blood cell count, and serum
      chemistry profile. These patients received prostate bed irradiation using 10-MV
      photons and a four-field technique. Doses ranged from 60.0 to 65.8 Gy in 1.8 to
      2.0 Gy fractions. Levels of serum PSA were monitored and decreased initially in
      all treated patients. In two patients, levels of PSA increased after this initial
      decrease. In 7 of the 11 patients (64%), PSA levels decreased to less than or
      equal to 0.3 ng/mL at last measurement. Radiotherapy resulted in no severe
      toxicity. None of the patients had developed clinical evidence of disease at the
      time of this report. Isolated elevations of serum PSA after prostatectomy reflect
      residual disease, and radiotherapy appears to effectively decrease the PSA levels
      in most cases. This effect appears to be accomplished by killing locally residual
      or recurrent cancer in the postoperative tumor bed.

PMID- 1374061
TI  - A report of RTOG 8206: a phase III study of whether the addition of single dose
      hemibody irradiation to standard fractionated local field irradiation is more
      effective than local field irradiation alone in the treatment of symptomatic
      osseous metastases.
AB  - Hemibody irradiation (HBI) in a single exposure is an effective and safe
      technique for palliation of symptoms due to widespread bony metastases (RTOG 78
      10). The present study (82-06) sought to explore the possibility that HBI added
      to local-field irradiation might delay the onset of metastases in the hemibody
      effected, as assessed by bone scans and X rays, and decrease the frequency of
      further treatment. The results of this clinical trial establish that 800 cGy of
      HBI is indeed causes micro-metastases to regress, perhaps completely. A total of
      499 patients were randomized to receive either HBI or no further treatment
      following completion of standard palliative local field irradiation (300 cGy x
      10) to the symptomatic site. Improvement was seen in time-to-disease progression
      at one year, 35% for local + HBI versus 46% on the local-only control arm. Time
      to-new disease in the targeted hemibody was also improved. At one year, 50% of
      patients on the local + HBI arm showed new disease compared to 68% on the local
      only arm. Furthermore, the median time-to-new disease within the targeted HBI
      area was 12.6 months for the local + HBI arm versus 6.3 months for patients in
      the local-only arm. Time-to-new treatment within the hemibody segment was also
      delayed. At one year, 76% of the local only group had been retreated versus 60%
      in the local + HBI arm. There were no fatalities and no radiation pneumonitis was
      seen in the local + HBI arm. Overall, the incidence of toxicities was low (5
      15%). The occurrence of severe hematopoetic toxicities were significantly
      different in the local + HBI arm, but they were transitory. One life-threatening
      thrombocytopenia occurred, for a limited time, indicating excellent tolerance to
      HBI. This clinical trial demonstrates that HBI has the potential to be used to
      treat systemic and occult metastases, particularly if both halves of the body can
      be treated.

PMID- 1374062
TI  - Bone metastasis consensus statement.

PMID- 1374063
TI  - A review of local radiotherapy in the treatment of bone metastases and cord
      compression.
AB  - Local radiotherapy plays an important role in the management of bone metastases.
      Because it is given with palliative intent to patients with limited, if variable,
      life expectancy, radiotherapy schedules need to be identified which give maximum
      patient benefit (short and long term) with minimum associated morbidity and
      minimum disruption of the patients' remaining life. For localized bone pain, a
      single fraction of radiotherapy, repeated if necessary, appears to fulfill these
      criteria in patients with a short life expectancy. There are, however, unanswered
      questions regarding fraction size and the adequacy of one fraction for long-term
      control and for all pathological tumor types. Only randomized trials can answer
      these questions. Uncertainties also exist regarding the precise indications for
      radiotherapy to prevent and treat pathological fractures and the optimal dose
      schedule which will provide adequate local tumor control without inhibiting bone
      healing or interfering with bone integrity. Because of the many variables,
      guidelines on selection of cases of spinal cord compression for decompression by
      surgery or radiotherapy are likely to be of more value than randomized
      prospective studies in this condition. Experimental work and clinical experience
      to date suggest an advantage for a few large fractions of radiotherapy, at least
      initially, to achieve a rapid response, but this too needs confirmation.
      Treatment decisions based on past teaching and local custom rather than on valid
      clinical trial data have led to considerable differences in clinical practice
      among radiotherapists. Bone metastases are common and warrant a great deal more
      experimental and clinical study than they have received to date.

PMID- 1374064
TI  - The role of radiation therapy in the treatment of brain metastases.
AB  - Whole brain irradiation is the most effective means for treating the patient with
      brain metastases with symptom relief occurring in 70 to 90% of patients. However,
      25-50% of patients with brain metastases will die due to eventual failure in the
      brain and therefore entry of patients into investigative trials is essential for
      continued progress in the management of this problem. For the patient who is not
      part of an investigative trial, short courses of radiation of 20 Gy in 1 week or
      30 Gy in 2 weeks are generally as effective as more prolonged courses and even
      shorter courses of treatment could be considered, particularly for the patient
      with an estimated survival of only 5-6 weeks. The importance of the treatment of
      brain metastases on the practice of radiation oncology is significant and
      comparable to other major cancers treated with radiation. It is critical that
      radiation oncologists can apply this treatment modality in a cost effective
      manner with careful consideration for the patients' quality of life.

PMID- 1374065
TI  - Prostate-specific antigen as a prognostic factor for prostate cancer treated by
      external beam radiotherapy.
AB  - The potential prognostic significance of prostate-specific antigen (PSA) serum
      concentrations was evaluated in 171 patients with stages A2 to C adenocarcinoma
      of the prostate treated with external beam radiotherapy. After a median follow-up
      of 17 months, 12 patients sustained relapse of disease and PSA levels were found
      to be prognostically significant in three ways. (a) Pretreatment PSA level: none
      of 59 patients with a pretreatment PSA level less than or equal to 4 ng/ml
      relapsed to date and only one developed a subsequently rising PSA profile; 7 of
      102 patients (7%) with a pretreatment PSA level in the range 4-40 ng/ml relapsed
      and 17 (17%) showed a rising PSA profile; 5 of 10 patients (50%) with a
      pretreatment PSA level greater than or equal to 40 ng/ml relapsed and six (60%)
      developed rising PSA values. The differences were significant and were maintained
      when patients were stratified by stage or grade. (b) PSA level at 6 months: for
      patients with pretreatment PSA levels in the range 4-40 ng/ml, a 6-month value
      greater than 2 ng/ml predicted a significantly worse outcome than a 6-month value
      less than 2 ng/ml. (c) Rising post-treatment PSA values: following a radiation
      related nadir in PSA levels, 24 patients experienced rising PSA values and 8
      (33%) relapsed at a median time of 5 months after onset of the rising values--a
      significantly higher relapse rate than observed in patients with non-rising PSA
      values. Whether the majority, or all, of the patients with rising PSA levels
      relapse, requires further follow-up. In conclusion, serum PSA levels are strong
      prognostic determinants of outcome following radiotherapy for prostate cancer and
      appear to add prognostic information independently of tumor stage and grade.

PMID- 1374066
TI  - Balbiani ring hnRNP substructure visualized by selective staining and electron
      spectroscopic imaging.
AB  - The Balbiani Rings (BR) in the polytene chromosomes of Chironomus salivary glands
      are intense sites of transcription. The nascent RNPs fold during transcription
      into 40-50-nm granules, containing in the mature transcript approximately 37-kb
      RNA. Using a new nucleic acid specific stain, osmium ammine B on Lowicryl
      sections, in combination with electron energy filtered imaging of sections
      containing BR granules, we demonstrate a RNA-rich particulate substructure (10-nm
      particle diameter; 10-12 particles per BR granule). Elemental imaging supports
      that these particles are enriched in phosphorus. The possible relationship of
      these RNA-rich particles to ribonucleosomes is discussed, as well as models for
      their arrangement in the mature BR granules.

PMID- 1374067
TI  - PKC epsilon-related kinase associates with and phosphorylates cytokeratin 8 and
      18.
AB  - A 40-kD protein kinase C (PKC)epsilon related activity was found to associate
      with human epithelial specific cytokeratin (CK) polypeptides 8 and 18. The kinase
      activity coimmunoprecipitated with CK8 and 18 and phosphorylated
      immunoprecipitates of the CK. Immunoblot analysis of CK8/18 immunoprecipitates
      using an anti-PKC epsilon specific antibody showed that the 40-kD species, and
      not native PKC epsilon (90 kD) associated with the cytokeratins. Reconstitution
      experiments demonstrated that purified CK8 or CK18 associated with a 40-kD
      tryptic fragment of purified PKC epsilon, or with a similar species obtained from
      cells that express the fragment constitutively but do not express CK8/18. A
      peptide pseudosubstrate specific for PKC epsilon inhibited phosphorylation of
      CK8/18 in intact cells or in a kinase assay with CK8/18 immunoprecipitates.
      Tryptic peptide map analysis of the cytokeratins that were phosphorylated by
      purified rat brain PKC epsilon or as immunoprecipitates by the associated kinase
      showed similar phosphopeptides. Furthermore, PKC epsilon immunoreactive species
      and CK8/18 colocalized using immunofluorescent double staining. We propose that a
      kinase related to the catalytic fragment of PKC epsilon physically associates
      with and phosphorylates cytokeratins 8 and 18.

PMID- 1374068
TI  - Slow axonal transport mechanisms move neurofilaments relentlessly in mouse optic
      axons.
AB  - Pulse-labeling studies of slow axonal transport in many kinds of axons (spinal
      motor, sensory ganglion, oculomotor, hypoglossal, and olfactory) have led to the
      inference that axonal transport mechanisms move neurofilaments (NFs)
      unidirectionally as a single continuous kinetic population with a diversity of
      individual transport rates. One study in mouse optic axons (Nixon, R. A., and K.
      B. Logvinenko. 1986. J. Cell Biol. 102:647-659) has given rise to the different
      suggestion that a significant and distinct population of NFs may be entirely
      stationary within axons. In mouse optic axons, there are relatively few NFs and
      the NF proteins are more lightly labeled than other slowly transported slow
      component b (SCb) proteins (which, however, move faster than the NFs); thus, in
      mouse optic axons, the radiolabel of some of these faster-moving SCb proteins may
      confuse NF protein analyses that use one dimensional (1-D) SDS-PAGE, which
      separates proteins by size only. To test this possibility, we used a 2-mm
      "window" (at 3-5 mm from the posterior of the eye) to compare NF kinetics
      obtained by 1-D SDS-PAGE and by the higher resolution two-dimensional (2-D)
      isoelectric focusing/SDS-PAGE, which separates proteins both by their net charge
      and by their size. We found that 1-D SDS-PAGE is insufficient for definitive NF
      kinetics in the mouse optic system. By contrast, 2-D SDS-PAGE provides
      essentially pure NF kinetics, and these indicate that in the NF-poor mouse optic
      axons, most NFs advance as they do in other, NF-rich axons. In mice, greater than
      97% of the radiolabeled NFs were distributed in a unimodal wave that moved at a
      continuum of rates, between 3.0 and 0.3 mm/d, and less than 0.1% of the NF
      population traveled at the very slowest rates of less than 0.005 mm/d. These
      results are inconsistent with the proposal (Nixon and Logvinenko, 1986) that 32%
      of the transported NFs remain within optic axons in an entirely stationary state.
      As has been found in other axons, the axonal transport system of mouse optic
      axons moves NFs and other cytoskeletal elements relentlessly from the cell body
      to the axon tip.

PMID- 1374070
TI  - In vitro paracrine regulation of human keratinocyte growth by fibroblast-derived
      insulin-like growth factors.
AB  - Human keratinocytes isolated from a skin biopsy and cultured in vitro on a feeder
      layer of irradiated fibroblasts reconstitute a stratified squamous epithelium
      suitable for grafting onto patients suffering from large burn wounds. Since
      conditioned medium from 3T3-J2 cells can partially substitute for the intact
      feeder-layer, we studied the possible involvement of insulin-like growth factors
      acting in a paracrine fashion. IGFs were measured (after Sephadex G-50 gel
      chromatography in acid conditions) in media conditioned by a feeder-layer of
      lethally irradiated 3T3-J2 fibroblasts on which keratinocytes were grown.
      Immunoreactive (IR) IGF-I, IGF-II, and IGF binding activity were present in the
      medium conditioned by the feeder-layer. The medium conditioned by keratinocytes
      showed nearly undetectable amounts of IR IGF-I and IGF-II, suggesting that
      keratinocytes are unable to synthesize IGFs peptides. Recombinant IGF-I and IGF
      II, and conditioned medium from 3T3-J2 cells, caused a dose-dependent increase of
      3H-thymydine incorporation in cultured keratinocytes. The stimulatory effect of
      IGF and of 3T3-J2 conditioned medium was inhibited by the MoAb Sm 1.2, which
      recognizes both IGF-I and IGF-II but not insulin, and by the MoAb alpha IR-3,
      which is a specific antagonist of type-I IGF receptor. Fetal mouse-derived 3T3-J2
      cells and adult human skin fibroblasts were equally able to sustain keratinocyte
      growth and in both cases addition of Sm 1.2 MoAb causes a 50% decrease in the
      keratinocyte number. When the non-IGF-producing BALB/c 3T3 cells were used as a
      feeder-layer, the keratinocytes number was similar to that observed with 3T3-J2
      and with human fibroblasts plus the Sm 1.2 MoAb. IGF-I and IGF-II restored the
      BALB/c 3T3 growth promoting activity to the level of 3T3-J2 and of normal human
      fibroblasts. Our results suggest that fetal mouse 3T3-J2 and human fibroblasts
      synthesize IGF peptides, while keratinocytes do not. Fibroblast-derived IGFs
      stimulate keratinocyte growth in a paracrine fashion, suggesting their role in
      the regulation of keratinocyte proliferation in skin growth and in wound healing.

PMID- 1374071
TI  - Analysis of inter-serotypic structural relationships of infectious bursal disease
      virus using detergent solubilization and radioimmunoprecipitation with monoclonal
      antibodies.
AB  - Monoclonal antibodies (MAbs) neutralizing only the infectious bursal disease
      virus strains (IBDV) belonging to serotype 1 also immunoprecipitated the
      heterologous major antigenic proteins of serotype 2 IBDV. Detergent
      solubilization followed by radioimmunoprecipitation assays (RIPA) using the MAbs
      revealed structural similarities between the conformation-dependent antigenic
      determinants of IBDV of the two existing serotypes. The presence of non-ionic
      detergent Triton X-100 determined the binding of altered proteins by MAbs in
      RIPA.

PMID- 1374069
TI  - Regulation of the VLA integrin-ligand interactions through the beta 1 subunit.
AB  - Integrins from the very late activation antigen (VLA) subfamily are involved in
      cellular attachment to extracellular matrix (ECM) proteins and in intercellular
      adhesions. It is known that the interaction of integrin proteins with their
      ligands can be regulated during cellular activation. We have investigated the
      regulation of different VLA-mediated adhesive interactions through the common
      beta 1 chain. We have found that certain anti-beta 1 antibodies strongly enhance
      binding of myelomonocytic U-937 cells to fibronectin. This beta 1-mediated
      regulatory effect involved both VLA-4 and VLA-5 fibronectin receptors. Moreover,
      anti-beta 1 mAb also induced VLA-4-mediated binding to a recombinant soluble form
      of its endothelial cell ligand VCAM-1. Non-activated peripheral blood T
      lymphocytes, unable to mediate VLA-4 interactions with fibronectin or VCAM-1,
      acquired the ability to bind these ligands in the presence of anti-beta 1 mAb.
      The anti-beta 1-mediated changes in the affinities of beta 1 integrin for their
      ligands were comparable to those triggered by different lymphocyte activation
      agents such as anti-CD3 mAb or phorbol ester. Adhesion of melanoma cells to other
      ECM proteins such as laminin or collagen as well as that of alpha 2-transfected K
      562 cells to collagen, was also strongly enhanced by anti-beta 1 mAb. These beta
      1-mediated regulatory effects on different VLA-ligand interactions do not involve
      changes in cell surface membrane expression of different VLA heterodimers. The
      anti-beta 1-mediated functional effects required an active metabolism,
      cytoskeleton integrity and the existence of physiological levels of intracellular
      calcium as well as a functional Na+/H+ antiporter. Beta 1 antibodies not only
      increased cell attachment but also promoted spreading and cytoplasmic extension
      of endothelial cells on plates coated with either fibronectin, collagen, or
      laminin as well as induced the rapid appearance of microspikes in U-937 cells on
      fibronectin. Moreover, both beta 1 integrin and the cytoskeletal protein talin
      colocalized in the anti-beta 1 induced microspikes. These results emphasize the
      central role of the common beta 1 chain in regulating different adhesive
      functions mediated by VLA integrins as well as cellular morphology.

PMID- 1374072
TI  - Comparison of hepatitis C virus markers in patients with NANB hepatitis.
AB  - 10 different HCV-specific assays and RT-PCR of the 5' untranslated region of HCV
      RNA were used to analyze sixty-four patients with chronic NANB liver disease. Po,
      CP-9 and C22 antigens are located in the putative core; C33c in the putative NS3;
      C100-3 in the putative NS3/4; KCL in the putative NS4/5 and C825 is located in
      the putative NS5. GOR protein is not part of the HCV genome, but antibodies to it
      appear to be present in response to a hepatitis C infection. Positive rates were
      91% for Po, 89% for CP-9, 94% for C22, 97% for C33c, 88% for C100-3 (Ortho, EIA),
      86% for C100-3 (Abbott, EIA), 84% for C100-3 (Ohtsuka, RIA), 88% for KCL, 59% for
      C825, 58% for GOR, and 83% for RT-PCR. There were 8 cases which were negative by
      all anti-C100 tests. 7 of these cases were positive by other anti-HCV markers
      and/or PCR suggesting the need for improved blood screening assays. There is a
      variation in the relative reactivity for different markers with different
      samples. Of the tests employed, anti C33c shows the highest positivity rate.

PMID- 1374073
TI  - Rapid identification of legionellae by a colony blot assay based on a genus
      specific monoclonal antibody.
AB  - We recently developed a monoclonal antibody immunoglobulin G2a (2125) recognizing
      a genus-specific epitope on the 60-kDa heat shock protein of all Legionella
      species. In the current study, this antibody was used in a colony blot enzyme
      linked immunosorbent assay for the rapid identification of Legionella cultures on
      agar plates. The whole protocol was completed in less than 2 h. All 59 Legionella
      species and serogroups that were tested gave a positive signal. No unspecific
      reactions with nonlegionellae were observed. This test is a rapid procedure for
      the identification of legionellae growing on agar medium to the genus level.

PMID- 1374074
TI  - Chemiluminescent universal probe for bacterial ribotyping.
AB  - We describe a novel procedure for direct covalent coupling of horseradish
      peroxidase to rRNA and ribotyping by using enhanced chemiluminescence. Compared
      with their 32P-end-labeled counterparts, chemiluminescent rRNA probes are stable
      and easy to synthesize and provide results as good as or superior to those
      obtained with isotopic labeling. Direct chemiluminescent labeling of Escherichia
      coli rRNA produces a sensitive, universal probe suitable for clinical laboratory
      use in the investigation of nosocomial outbreaks.

PMID- 1374075
TI  - Microheterogeneity within rRNA of Mycobacterium gordonae.

PMID- 1374076
TI  - Detection of the etiologic agent of human ehrlichiosis by polymerase chain
      reaction.
AB  - Polymerase chain reaction (PCR) primers derived from a variable region of the 16S
      rRNA gene sequence were used to amplify DNA specifically from Ehrlichia
      chaffeensis (the recently proposed name for the etiologic agent of human
      ehrlichiosis). The 389-bp product defined by the specific primers was not
      detected when DNA samples from any of the other recognized species of Ehrlichia
      were used as amplification templates. When the PCR was applied to five suitable
      blood specimens obtained from patients subsequently shown to be serologically
      positive for E. chaffeensis, all five were positive. The same technique was
      applied to a total of six control blood specimens, three from febrile patients
      who had no serologic evidence of infection with Ehrlichia or Rickettsia species
      and three from patients diagnosed with Rocky Mountain spotted fever, and all six
      were negative. A chemiluminescent, group-specific oligonucleotide probe was shown
      to hybridize only with the PCR products obtained upon amplification of the five
      blood specimens from patients serologically diagnosed as having human
      ehrlichiosis. The results indicate that PCR, coupled with a nonisotopic method of
      confirming the identity of the PCR product, is a highly specific and efficient
      method of detecting the agent of human ehrlichiosis in blood. The results also
      suggest that E. chaffeensis is the sole etiologic agent of human ehrlichiosis in
      the United States. The technique was also applied to four ticks that were
      positive by direct immunofluorescence for Ehrlichia species, and one tick was PCR
      positive, indicating that E. chaffeensis DNA can be detected in ticks harboring
      this organism, although the sensitivity may be low.

PMID- 1374077
TI  - Identification of Chlamydia pneumoniae by DNA amplification of the 16S rRNA gene.
AB  - Chlamydia pneumoniae is an important cause of respiratory disease in humans, but
      diagnosis of C. pneumoniae is hindered by difficulties in the in vitro growth of
      the organism. In order to improve detection and identification, we recently
      developed a polymerase chain reaction (PCR) assay which uses oligonucleotide
      primers specific for C. pneumoniae. The nucleic acid sequence was determined for
      the 16S rRNA of C. pneumoniae, and regions in which C. pneumoniae differed from
      both Chlamydia psittaci and Chlamydia trachomatis were identified.
      Oligonucleotide primers corresponding to these unique regions were then
      synthesized and used in a PCR for the detection of C. pneumoniae. The C.
      pneumoniae-specific primers permitted the identification of six isolates of C.
      pneumoniae, but no reaction was observed with the 15 serovars of C. trachomatis
      or two strains of C. psittaci. PCR should prove to be valuable in confirming the
      identification of C. pneumoniae and in the diagnosis of C. pneumoniae infections.

PMID- 1374078
TI  - Analysis of rRNA restriction fragment length polymorphisms from Bacteroides spp.
      and Bacteroides fragilis isolates associated with diarrhea in humans and animals.
AB  - The Escherichia coli rRNA operon rrnB was used as a 32P-labeled hybridization
      probe in Southern blots of genomic DNAs from representative strains of the
      saccharolytic, gram-negative, obligate anaerobes of the genus Bacteroides.
      Control experiments with the B. fragilis type strain ATCC 25285 established that
      nearly identical rRNA fragment patterns were produced when either the E. coli
      rrnB gene probe or homologous rRNA isolated from B. fragilis was used as the
      probe. In addition, it was shown that a specific 16S or 23S rrnB gene probe also
      could be used to produce fragment patterns suitable for analysis. Thirty-one
      strains from 8 of the 10 recognized Bacteroides species were then examined. The
      resulting autoradiographs revealed specific fragment patterns for all but one (B.
      ovatus) of the species tested. Restriction fragment length polymorphisms were
      observed for many of the strains tested, but these differences did not hinder
      species classification. The five B. ovatus strains examined did not form a
      distinct group, and their rRNA fragment patterns displayed a marked
      heterogeneity. The same approach was applied to a unique set of enterotoxin
      producing B. fragilis strains isolated from animals and humans with diarrhea. The
      results demonstrated that these strains were in fact B. fragilis and that they
      produce rRNA fragment patterns closely related to those of the type strain ATCC
      25285. This set of strains did not appear to form a separate subgroup or genotype
      within the B. fragilis species, and there were no distinguishable restriction
      fragment length polymorphisms that could be used to specifically separate
      enterotoxin-producing strains from nonenterotoxigenic strains.

PMID- 1374079
TI  - Specific immunofluorescent staining of pathogenic treponemes with a monoclonal
      antibody.
AB  - Two hybrid cell lines which produced mouse monoclonal antibody to the DAL-1
      street strain of Treponema pallidum subsp. pallidum were established. These
      monoclonal antibodies strongly reacted with T. pallidum subsp. pallidum (Nichols
      strain, DAL-1, and two other street strains, strains MN-1 and MN-3) and T.
      pallidum subsp. pertenue by indirect microimmunofluorescent antibody and enzyme
      linked immunosorbent assay techniques, but they did not react with normal rabbit
      testicular tissue. These monoclonal antibodies did not react with nonpathogenic
      treponemes, such as T. phagedenis Reiter, T. denticola MRB, T. refringens
      Noguchi, or other spirochetes, such as Borrelia burgdorferi and Leptospira
      interrogans serovar pomona in microimmunofluorescent antibody smear slides or in
      Western blots (immunoblots). While unlabeled antibodies are useful for
      investigating the antigenic structures of T. pallidum, we labeled these
      monoclonal antibodies with fluorescein isothiocyanate and used them for
      diagnosing syphilis by direct staining of lesion exudate or T. pallidum subsp.
      pallidum in formalin-fixed tissues from patients suspected of having syphilis.
      Both monoclonal antibodies were directed against antigens of T. pallidum subsp.
      pallidum with a molecular weight of 37,000 as determined by the Western blotting
      technique.

PMID- 1374081
TI  - Nitric oxide synthetase (NOS)-containing sympathoadrenal cholinergic neurons of
      the rat IML-cell column: evidence from histochemistry, immunohistochemistry, and
      retrograde labeling.
AB  - Nitric oxide synthetase (NOS) can be selectively stained in neurons by either
      NADPH-diaphorase (i.e., NOS)-histochemistry or immunohistochemistry with
      antibodies raised against NOS, which apparently label identical reactive sites
      (Hope, B.T., G.J. Michael, K.M. Knigge, and S.R. Vincent, Proc. Natl. Acad. Sci.
      USA 88:2811-2814, '91). We provide histochemical evidence for the existence of a
      neuron-specific NOS-activity in autonomic neurons of the thoracic spinal cord.
      Among the four main preganglionic cell clusters investigated at mid-thoracic
      levels, Th7-10, the intermediolateral (IML)-cell column was the most prominently
      stained cell group. The histochemical staining was absent in other spinal cord
      neurons and non-neuronal cells, e.g., GFAP-positive glial cells. Staining was
      completely blocked by N omega-nitro-L-arginine (L-NNA), a potent NOS-inhibitor
      for brain and peripheral autonomic neurons, but was still observed in the
      presence of another NOS-inhibitor, N omega-monomethyl-L-arginine (MeArg). The NOS
      activity co-localized with nearly half of the ChAT-immunostained neurons located
      in the mid-thoracic IML-cell column as quantified by cell counts in single and
      double-stained tissue sections. We conclude that NOS-activity-containing neurons
      represent a distinct group among cholinergic IML-neurons, which suggests a more
      general function of this newly defined subpopulation of the spinal cord autonomic
      system. In vivo Fast blue retrograde labeling combined with histochemical
      staining and immunostaining revealed that sympathoadrenal projection neurons
      belong to the distinct NOS and ChAT-positive IML-cell group.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1374080
TI  - Rapid detection of respiratory syncytial virus in nasopharyngeal aspirates by
      reverse transcription and polymerase chain reaction amplification.
AB  - A rapid method for detection of respiratory syncytial virus (RSV) in
      nasopharyngeal aspirates, involving a combination of reverse transcription and
      polymerase chain reaction amplification (RT-PCR), has been developed. The RT-PCR
      assay employs oligonucleotide primers specific for the region of the RSV genome
      which encodes the F1 subunit of the fusion (F) glycoprotein. Other respiratory
      viruses do not give a positive reaction. The RT-PCR assay was tested on 202
      nasopharyngeal aspirates collected from children with clinical signs of
      respiratory infection, and the results from RT-PCR were compared with those
      obtained from virus culture and direct detection by enzyme immunoassay (EIA). RT
      PCR results were positive in 118 of 125 samples from which RSV was cultured, as
      well as in 4 of 7 samples which were culture negative but EIA positive. RT-PCR
      results were negative in 68 of 70 culture-negative, EIA-negative samples, which
      included 11 samples from which other respiratory viruses were isolated. The
      speed, sensitivity (94.6%), and specificity (greater than 97%) of the RT-PCR
      assay suggest that this technique could be useful for rapid detection of RSV in
      clinical samples.

PMID- 1374082
TI  - Premotor descending neurons responding selectively to local visual stimuli in
      flies.
AB  - The responses of dorsal descending neurons suggest great versatility of the
      visual system in detecting features of the visual world. Although wide-field
      motion-sensitive neurons respond to symmetric visual flow fields presented to
      both eyes, other neurons are known to respond selectively to asymmetric movement
      of the visual surround. The present account distinguishes yet a third class of
      descending neurons (DNs) that is selectively activated by local presentation of
      moving gratings or small contrasting objects. Excitation of these DNs in response
      to local motion contrasts with their inhibitory responses to wide-field motion.
      The described DNs invade dorsal neuropil of the pro- and mesothoracic ganglia
      where they converge with other morphologically and physiologically characterized
      descending elements. Axon collaterals of DNs visit thoracic neuropil containing
      the dendrites of motor neurons supplying indirect neck and flight muscles. The
      present results are discussed with respect to the organization of small-field
      retinotopic outputs from the lobula, and with respect to the parallel projection
      of many information channels from the brain to the neck and flight motors.

PMID- 1374083
TI  - Organization of inferior olivary projections to the flocculus and ventral
      paraflocculus of the rat cerebellum.
AB  - The climbing fiber projection to the rat flocculus and adjacent ventral
      paraflocculus was investigated by using Phaseolus vulgaris-leucoagglutinin as an
      anterograde and horseradish peroxidase as a retrograde tracer. Large injections
      of horseradish peroxidase in the flocculus and ventral paraflocculus indicated
      that the climbing fibers to this region are derived exclusively from any of the
      following contralateral olivary regions: the dorsal cap of Kooy, the
      ventrolateral outgrowth, the caudal half of the ventral leaf of the principal
      olive near its lateral bend, and the rostral pole of the medial accessory olive.
      Subsequent anterograde and retrograde studies with small injections demonstrated
      that the latter area projects to the C2 zone, which runs caudally in the ventral
      paraflocculus and enters the caudal most aspect of the flocculus. The ventral
      leaf of the principal olive is connected to a D zone in the cerebellar hemisphere
      and paraflocculus, which, upon entering the ventral paraflocculus, divides into a
      caudal and rostral strip, termed FD and FD', respectively. The dorsal cap and the
      ventrolateral outgrowth each project to two distinct zones in the flocculus and
      part of the ventral paraflocculus. Two floccular zones, which are continuous with
      the parafloccular FD and FD' zones, receive their climbing fibers from the
      ventrolateral outgrowth. Two other zones, (FE and FE') receive their climbing
      fibers from the dorsal cap. The FE' zone is found at the rostral pole of the
      flocculus and is followed caudalwards by the FD', FE, FD, and C2 zones,
      respectively. The rostromedial part of the dorsal cap is connected to the
      continuation of the FE zone into the ventral paraflocculus. The observation that
      the dorsal cap and the ventrolateral outgrowth are both connected to a set of two
      alternating zones of floccular/ventral parafloccular Purkinje cells is in
      agreement with recent studies in the rabbit, and suggests that these zones
      reflect functionally distinct and discrete units related to specific aspects of
      visuomotor control.

PMID- 1374084
TI  - Claustrum in the hedgehog (Erinaceus europaeus) brain: cytoarchitecture and
      connections with cortical and subcortical structures.
AB  - The cytoarchitecture of the claustrum in the hedgehog (Erinaceus europaeus)
      brain, the morphology of its neurons, and the efferent connections with cortical
      and subcortical structures were studied with the Nissl and Kluver-Barrera, the
      Golgi, and the horseradish peroxidase methods. It was found that the claustrum is
      a well developed nucleus in the hedgehog telencephalon and, as in other mammals,
      is divided into dorsal and ventral parts. In Golgi-stained sections, spiny
      multipolar cells are the predominant neurons of both the dorsal and the ventral
      claustrum and are projection neurons. Aspiny multipolar neurons with fewer, often
      beaded, dendrites constitute a minority in both divisions and are interneurons.
      Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the
      prefrontal, motor, somatosensory, auditory and visual areas, and HRP or WGA-HRP
      injections in the thalamus showed that: (1) the claustroneocortical projections
      originate in the dorsal claustrum and are distributed to the entire neocortex;
      these projections are mainly ipsilateral but some also originate contralaterally;
      (2) the claustroneocortical projections show a rough topographic organization;
      there exists a substantial degree of overlap; and (3) the claustrothalamic
      projection, arising throughout the dorsal claustrum, is strictly ipsilateral. No
      evidence of a thalamoclaustral projection was found. The present results suggest
      that, although the hedgehog has been referred to as a "paleocortical mammal"
      owing to the great development of its rhinencephalic structures in comparison
      with its small neocortex, the dorsal claustrum is well developed and is connected
      with all neocortical areas as well as with the thalamus, establishing it as a key
      structure in the hedgehog forebrain.

PMID- 1374085
TI  - Dorsal root ganglion neurons projecting to the dorsal column nuclei of rats.
AB  - Dorsal root ganglion (DRG) neurons may give origin to ascending branches that
      terminate in the dorsal column nuclei (DCN); uncertainties still exist with
      regard to the proportion of these neurons in different DRGs and to the type of
      these neurons. The percentage and size of neurons that project to the DCN were
      determined in a large number of DRGs by means of the retrograde transport of
      colloidal gold-labeled wheat germ agglutinin conjugated to enzymatically inactive
      horseradish peroxidase (WGAapoHRP-AU). A total of 16,239 neurons was tallied in
      80 DRGs from nine rats; 3,240 (20%) of these were retrogradely labeled by the
      tracer injected in the DCN. Percentages of DCN projecting neurons vary
      considerably at different segmental levels: they are higher in cervical (up to
      63%) than in thoracic (up to 31% for T1, up to 12% for thoracic DRGs below T1) or
      lumbar DRGs (up to 15%). At cervical levels highest percentages were encountered
      in C6, C7, and C8 and lowest percentages in C2-C4. At lumbar levels highest
      percentages were encountered in L4 and lowest in L1 and L6. When considering the
      soma size of DRG neurons it appears that: 1) there are more large cells, labeled
      and unlabeled, at cervical (38%) than at lumbar levels (30%) and more at lumbar
      than at thoracic levels (23%); 2) at every level, most labeled, i.e., projecting,
      neurons are large; and 3) DRGs with the highest proportions of large vs. small
      cells contain the highest percentages of DCN projecting neurons. These results
      represent the first attempt at establishing the percentages and soma size of DCN
      projecting neurons from a large number of DRGs and at comparing the contribution
      to these nuclei from cervical, thoracic, and lumbar DRGs. Some of the differences
      in the ratio of projecting neurons at different levels may be explained on the
      basis of well-known anatomical features, e.g., the projections to the Clarke's
      column of many DRG neurons in lumbar ganglia. The contribution of virtually
      exclusively large DRG neurons to the DCN, suggested by indirect or incomplete
      evidence, is demonstrated by the present retrograde labeling and soma size
      measurements. The results relate to the functional component of peripheral
      receptors that relay their input via the dorsal columns and do not seem to
      support a recent suggestion that a sizeable fraction of unmyelinated primary
      afferents ascend in the dorsal columns to terminate in the DCN.

PMID- 1374086
TI  - Trigeminocerebellar projections to the posterior lobe in the cat, as studied by
      anterograde transport of wheat germ agglutinin-horseradish peroxidase.
AB  - Cerebellar projections of the nucleus interpolaris and oralis of the spinal
      trigeminal nucleus were studied in the cat by anterograde transport of wheat germ
      agglutinin conjugated to horseradish peroxidase (WGA-HRP). Injections of WGA-HRP
      into these nuclei labeled many mossy fiber terminals mainly ipsilaterally in the
      rostral folium of lobule IX (IXa or IXa + b), the simple lobule, the anterior
      part (sublobule A) of the paramedian lobule and the posterior part of crus II.
      Labeled terminals were also seen in the anterior lobe, lobules VI and VII, the
      anterior part of crus I, and the paraflocculus dorsalis. Projection fields in the
      horizontal plane of lobules were reconstructed from a series of transverse
      sections through each folium of lobule IX, the paramedian lobule, and the
      posterior part of crus II on the ipsilateral side. In sublobule IXa + b, labeled
      terminals were distributed in five longitudinal areas extending along the
      apicobasal axis of the sublobule. These five areas were located in the apical two
      thirds of the ipsilateral half of the sublobule. Labeled terminals were
      distributed in five longitudinal areas in sublobule A (the rostral part) of the
      paramedian lobule. In the posterior part of crus II, four aggregations of labeled
      terminals were present in cross sections through a lobule. They were distributed
      in the apicobasal extent of the lobules. The present study indicates that the
      projection fields of trigeminocerebellar fibers are longitudinally arranged along
      the apicobasal axis of the cerebellar lobules.

PMID- 1374087
TI  - Organization of parabrachial nucleus efferents to the thalamus and amygdala in
      the golden hamster.
AB  - While gustation in the hamster has been extensively studied at the behavioral and
      physiological level, very little is known about the central anatomy of the taste
      system. The purpose of this study was to trace the connections of the
      parabrachial nucleus (PBN) in the golden Syrian hamster (Mesocricetus auratus)
      using wheat germ agglutinin-conjugated horseradish peroxidase. The PBN is the
      site of the second central synapse for the ascending gustatory system and
      receives taste afferents from the nucleus of the solitary tract. Following large
      injections into the PBN, anterogradely transported label was seen in the lateral
      hypothalamus, dorsal thalamus, bed nucleus of the stria terminalis, and amygdala.
      The anatomy of the two primary targets, the ventral posteromedial thalamus and
      central nucleus of the amygdala, is described based on Nissl-stained material,
      and acetylcholinesterase and NADH dehydrogenase histochemistry. Injections into
      these two regions revealed different patterns of efferents within the PBN.
      Following injections into the thalamus, retrogradely labelled cell bodies were
      distributed throughout the PBN subdivisions bilaterally, but concentrated in the
      central medial (CM) and external lateral (EL) subdivisions. Following injections
      into the amygdala, retrogradely labelled cell bodies were primarily in the
      ipsilateral PBN EL, while anterogradely transported label was distributed
      throughout much of the ipsilateral PBN. The majority of CM efferents projecting
      to the thalamus were elongate cells, whereas the majority of CM efferents to the
      amygdala were round-oval cells. These results indicate that the ascending central
      gustatory system changes from a serial pathway (nucleus of the solitary tract
      PBN) to a parallel organization consisting of two major projections, the
      parabrachio-thalamo-cortical and parabrachio-amygdaloid pathways.

PMID- 1374088
TI  - Position of the American Dietetic Association: nutrition in comprehensive program
      planning for persons with developmental disabilities.

PMID- 1374089
TI  - [Massive fetal-maternal hemorrhage at term associated with a choriocarcinoma].
AB  - A case of malignant choriocarcinoma produced a major feto-maternal transfusion at
      term. This was proven using routine Kleihauer's test. The newborn died on the 5th
      day of life from haemorrhagic shock. The diagnosis of choriocarcinoma was made
      when acute post-partum haemorrhage occurred together with a high level of Beta
      HCG. The patient was cured by the use of Methotrexate followed by four courses of
      tri-chemotherapy (Methotrexate, Actinomycin and Cyclophosphamide). After
      treatment for secondary infertility, the patient had two normal pregnancies. This
      case makes possible to point out again the possible association of a positive
      Kleihauer test with choriocarcinoma. It also points out strongly the value of
      carrying out Beta HCG testing when bleeding occurs post-partum. Early diagnosis
      improves the maternal prognosis and allows conservative treatment to be carried
      out in cases of choriocarcinoma in young women.

PMID- 1374090
TI  - Expression of alpha-lactalbumin, alpha-S1-casein, and lactoferrin genes is
      heterogeneous in sheep and cattle mammary tissue.
AB  - We used 35S-labeled cRNA probes to localize the sites of alpha-lactalbumin, alpha
      S1-casein, and lactoferrin mRNA synthesis in sheep and forcibly weaned cattle
      mammary tissue. Expression of alpha-lactalbumin was absent in three of four
      "virgin" glands studied, present in some alveoli of "pregnant" glands but not in
      others, despite a similar histological appearance. In the early lactating gland,
      expression was high in those alveoli with few fat globules in their cells and
      lumen and was absent in alveoli with abundant fat globules. These observations
      suggest either that alpha-lactalbumin gene expression is linked to the long-term
      secretory activity of cells and falls once cells are resting or regressing, or
      that there are cyclical variations in expression, or that in the lactating gland
      some groups of epithelial cells are synthesizing alpha-lactalbumin and some are
      synthesizing fat. Expression patterns of alpha-S1-casein were similar to those of
      alpha-lactalbumin. Lactoferrin, in contrast, was expressed almost exclusively in
      the "fatty alveoli" of both species. Our results show that dramatic variations in
      milk gene expression can occur throughout the mammary gland of sheep and cattle
      and that at no stage of pregnancy, lactation, or involution can the gland be
      considered metabolically homogeneous.

PMID- 1374091
TI  - Antigenic profile of the human lacrimal gland.
AB  - The antigenic profile of 13 normal formalin-fixed, paraffin-embedded human main
      and accessory lacrimal glands, biopsied from patients aged 11 to 78 years, was
      studied using a panel of 27 polyclonal and monoclonal antibodies. Secretory cells
      of lacrimal acini reacted with antibodies to S-100 protein and simple epithelium
      type cytokeratins CK 7, CK 8, CK 18, and CK 19. Their luminal membranes were
      labeled with antibodies to carcinoembryonic antigen, epithelial membrane antigen,
      and epithelial glycoproteins recognized by Ber-EP4. Myoepithelial cells were
      often immunopositive for S-100 protein, vimentin, glial fibrillary acidic protein
      (GFAP), and alpha-smooth muscle actin. More rarely, they reacted with antibodies
      recognizing CK 5, CK 13, and CK 14, which consistently labeled the basal cells of
      lacrimal ducts. Unlike myoepithelial cells, basal ductal cells were
      immunopositive for CK 7, CK 8, CK 18, and CK 19. In main excretory ducts,
      dendritic melanocyte-like cells co-expressing vimentin and S-100 protein
      intermingled with ductal epithelial cells. The luminal cells of lacrimal ducts
      basically paralleled secretory cells in their antigenic profile, although they
      lacked Ber-EP4 and were immunopositive for CK 4. Antibodies to neuron-specific
      enolase and synaptophysin reacted with nerve fibers among negatively reacting
      secretory acini. This antigenic profile closely parallels that of salivary glands
      and provides a basis for studies of lacrimal gland pathology.

PMID- 1374092
TI  - Characterization of an antigenic determinant preferentially expressed by type I
      epithelial cells in the murine thymus.
AB  - A hamster monoclonal antibody (MAb), designated 8.1.1, was raised against murine
      thymic stromal cell lines and was found to react with cell surface molecules
      expressed by a morphologically distinct population of epithelial cells of the
      murine thymus comprising the subcapsular environment, cells investing vascular
      structures throughout the thymus, and some of the cellular elements in the
      medulla. The epithelial nature of the labeled cells was confirmed with
      immunoelectron microscopy. Reactivity with MAb 8.1.1 was associated with thymic
      epithelial cells in contact with basal laminae. Ontological studies of thymic
      tissue demonstrated that the epitope recognized by this MAb was expressed before
      Day 14 of gestation, although the restricted subcapsular and medullar expression
      of 8.1.1 was not apparent until sometime after birth. MAb 8.1.1 also reacted with
      a number of extra-thymic tissues, including lamina propria of gut, glomeruli and
      tubules in the kidney, mesothelia covering a number of organs, and the dermis and
      epidermis of skin. Within the epidermis, reactivity of MAb 8.1.1 was largely
      restricted to basal epithelial cells. Immunochemical analysis of 8.1.1 reactivity
      with detergent-soluble extracts of thymic stromal cell lines and thymus tissue
      indicated that detergent-soluble extracts of thymic stromal cell lines and thymus
      tissue indicated that the epitope recognized by this MAb was associated with a
      glycoprotein bearing terminal N-acetylglucosamine residues and possessing an Mr
      of approximately 36-38 KD under reducing or non-reducing conditions.

PMID- 1374093
TI  - Immunohistological demonstration of pyruvate kinase isoenzyme type L in rat with
      monoclonal antibodies.
AB  - Four monoclonal antibodies (MAb) specific for the L-type isoenzyme of rat
      pyruvate kinase (L-PK) were produced and characterized. They detect at least two
      different epitopes of the isoenzyme, as shown in interference binding assay and
      Western blot analysis after peptide mapping. The MAb were used in immunohistology
      to demonstrate the L-PK isoenzyme in paraffin-embedded normal rat tissues. L-PK
      was found only in hepatocytes, kidney proximal tubules, islet cells of pancreas,
      and epithelial cells of the villi of small intestine. The content of L-PK in
      hepatocytes was often lower in the periportal areas as compared with the
      periveneous zone. In kidneys a clearcut difference in L-PK content and
      distribution existed between male and female rats. Male animals possessed more L
      PK in the kidney cortex than females. The L-PK content in the inner cortical zone
      (straight proximal tubules) was higher than in the outer cortical zone
      (convoluted proximal tubules) in kidneys of males. In contrast, female rats
      displayed less L-PK in the inner than in the outer cortical zone of the kidneys.
      Only some of them exhibited the same amount of the isoenzyme in both parts of the
      kidney proximal tubules.

PMID- 1374095
TI  - CD4 epitope masking by gp120/anti-gp120 antibody complexes. A potential mechanism
      for CD4+ cell function down-regulation in AIDS patients.
AB  - The in vitro suppressive effect of gp120 and gp120/anti-gp120 antibody is well
      known but not yet proven to operate in vivo. We report findings consistent with
      the presence of gp120/anti-gp120 antibody complexes on CD4+ lymphocytes from HIV
      infected patients with advanced disease. PBMC from most AIDS patients showed
      selective masking of the CD4 epitope associated with the gp120 binding site;
      immunoprecipitation of PBMC with anti-CD4 mAb disclosed high amounts of IgG bound
      to CD4 receptors. Antibodies against HIV env proteins, but not other HIV products
      or CD4 Ag, were detected in purified CD4+ cell culture supernatants; in vitro
      culture was associated with normalization of both CD4 expression in PBMC and the
      lymphocyte proliferative response to anti-CD3. gp120 presence could not be
      directly demonstrated, but findings strongly suggested that CD4+ lymphocytes from
      most HIV-infected patients with advanced disease were covered with gp120/anti
      gp120 antibody complexes, which are responsible for down-regulation of surface
      CD4 expression as well as functional lymphocyte impairment; this event may
      represent an important mechanism in the pathogenesis of HIV-associated
      immunodeficiency.

PMID- 1374094
TI  - Identification and analysis of a novel human surface CD5- B lymphocyte subset
      producing natural antibodies.
AB  - The production of "natural" autoantibodies or antibodies, i.e., Ig that bind a
      variety of self- and/or exogenous Ag and arise independently of known
      immunization, is though to be a feature of CD5+ B lymphocytes. To determine
      whether other lymphocyte subsets exist that might be committed to the production
      of natural antibodies, human peripheral blood B cells were sorted on the basis of
      surface CD5 expression and differential expression of surface CD45RA
      (CD5+CD45RAintermediate(int), CD5-CD45RAlow(lo), and CD5-CD45RAhigh(hi)), and
      analyzed for the type of Ig produced after EBV infection and culture. Like their
      CD5+ counterparts, most CD5-CD45RAlo B lymphocytes were precursors of cells
      producing IgM, a major proportion of which displayed the Ag-binding features of
      natural antibodies. In contrast, CD5-CD45RAhi B cells comprised a high frequency
      of IgG-producing cell precursors, possibly including memory B lymphocytes. Six of
      seven IgM mAb generated from sorted CD5-CD45RAlo B cells and three of four IgM
      mAb from sorted CD5+ B cells were polyreactive, binding with different affinities
      (Kd, 10(-5) to 10(-8) M) to two or more Ag; the remaining mAb from CD5-CD45RAlo
      and the mAb from CD5+ B cells each bound to a single Ag (Kd, 10(-7) to 10(-8) M),
      beta-galactosidase and ssDNA, respectively. CD5-CD45RAlo B cells account for 4.1
      +/- 1.2% (mean +/- SD in 11 healthy subjects; CD5+ B cells, 23.3 +/- 6.9%) of
      total B lymphocytes and display the features of quiescent cells. In a given
      individual, the number of CD5-CD45RAlo B cells remains constant over time. CD5
      CD45RAlo and CD5+ B cells bear surface CD11b and CD14, at densities and/or
      frequencies apparently higher than those of CD5-CD45RAhi B lymphocytes. Despite
      their surface CD5- phenotype, CD45RAlo B cells express CD5+ mRNA at levels
      comparable with those of CD5+ B lymphocytes, whereas CD5-CD45RAhi B cells express
      only trace amounts of CD5 mRNA. The commitment to natural antibody production and
      the degree of CD5 mRNA expression suggest that the newly defined CD5-CD45RAlo B
      cell subset is related to CD5+ B lymphocytes, and may constitute the human
      homologue of the mouse Ly-1-"sister" B cell population.

PMID- 1374096
TI  - Induction of VCAM-1 and ICAM-1 on human neural cells and mechanisms of
      mononuclear leukocyte adherence.
AB  - We propose that leukocyte-derived cytokines induce the expression of adhesion
      molecules on the surface of neural cells that facilitates the subsequent
      attachment of leukocytes. Leukocyte adherence may contribute to some of the
      neural cell injury seen with various inflammatory diseases of the nervous system.
      With an in vitro model system, we have shown that mononuclear leukocytes bind to
      human neuroblastoma and cortical neuron cells only after the neural cells are
      stimulated with TNF-alpha. TNF-alpha stimulates expression of vascular cell
      adhesion molecule-1 (VCAM-1) in both of these neural cell lines. VCAM-1 mRNA is
      increased and VCAM-1 protein can be identified on the neural cell membranes with
      a new VCAM-1-specific mAb, CL40/2 F8. TNF-alpha also induces ICAM-1 in both of
      these neural cell lines. Leukocyte beta 1 (CD29) and beta 2 (CD18) integrins and
      their respective ligands, ICAM-1 and VCAM-1, on neural cells appear to be the
      dominant ligands mediating MNL:neural cell adhesive interactions. mAb to CD18
      block 32 to 57% of the MNL binding to neural cells; similar inhibition is seen
      with mAb to ICAM-1. mAb to CD29 block 16 to 17% of the MNL binding to the neural
      cells suggesting that leukocyte beta 1 integrins and neural VCAM-1 may be a
      second route for MNL:neural cell interactions. Addition of both anti-CD18 and
      anti-CD29 mAb have an additive blocking effect; both ligand pairs may participate
      in MNL adhesion to neural cells, reminiscent of the multiplicity of ligands used
      by MNL when binding to endothelium.

PMID- 1374097
TI  - Cytotoxic T lymphocytes from HIV-1 seropositive individuals recognize
      immunodominant epitopes in Gp160 and reverse transcriptase.
AB  - The CTL response to HIV-1 is more vigorous than for any known human pathogen and
      may be a significant factor in preventing the progression to symptomatic disease.
      T cell lines, generated by non-specific stimulation with PHA and IL-2, may be
      reproducibly used to identify HIV-1 isolate-invariant epitopes recognized by the
      CTL of infected individuals. The CTL response in each of 12 infected individuals
      to envelope and reverse transcriptase (RT) is dominated by the recognition of one
      or two viral isolate-invariant epitopes. Seven subjects respond to a single gp160
      epitope; three subjects recognize 2 gp160 epitopes. There is a significant
      increase in recognition of epitopes in the C terminal 104 amino acids of gp41 (p
      less than 0.002); in fact 40% of the subjects that respond to gp160 recognize the
      C terminal 20-mer. The CTL-mediated lysis of gp160-expressing targets is MHC
      restricted, but not all individuals that share the same serologically defined
      class I-restricting element respond to the same epitope. Recognition of the
      terminal 20mer is restricted by both A30 and B8. The response to RT in six
      subjects is distributed over the RT protein. The six subjects recognize four
      separate regions defined by truncated RT-vaccinia recombinants, but none of the
      subjects' CTL demonstrate significant recognition of the RT epitope identified in
      H-2k mice and some humans.

PMID- 1374098
TI  - Regulation of the effector stages of experimental autoimmune encephalomyelitis
      via neuroantigen-specific tolerance induction. II. Fine specificity of effector T
      cell inhibition.
AB  - Ag-specific tolerance induced by the i.v. administration of splenocytes coupled
      with mouse spinal cord homogenate, containing a mixture of myelin Ag,
      dramatically inhibits development and expression of clinical and histologic signs
      of both active and adoptive forms of relapsing experimental autoimmune
      encephalomyelitis (R-EAE) in the SJL/J host. Here we examined the dose
      dependency, route of tolerogen administration, and fine neuroantigen specificity
      of inhibition of adoptive R-EAE. Expression of clinical R-EAE induced by a
      polyclonal population of bovine myelin basic protein (MBP)-specific effector T
      cells was dramatically inhibited in a dose-dependent manner following the i.v.,
      but not s.c. or i.p., injection of MBP-coupled splenocytes. The exquisite Ag
      specificity of the inhibition was evident by the observation that splenocytes
      coupled with intact bovine MBP or species variants of MBP homologous with bovine
      MBP within the major encephalitogenic region (amino acids 84-104), but not with
      proteolipid protein or mouse kidney homogenate, were able to suppress disease
      expression. Splenocytes coupled with the MBP84-104 peptide, containing a nested
      set of the major SJL/J encephalitogenic epitopes, completely inhibited peptide
      specific T cell responses, but only partially inhibited the expression of disease
      transferred by T cells specific for intact MBP, suggesting the participation of T
      cell responses specific for additional MBP determinants in disease pathogenesis.
      However, splenocytes coupled with previously identified minor SJL/J
      encephalitogenic epitopes (MBP91-104 or MBP17-27), or with the Lewis rat major
      encephalitogenic epitope (MBP68-86), did not suppress disease expression.
      Collectively, the results demonstrate that MBP84-104-specific T cells and T cells
      specific for an as yet unidentified MBP epitope(s) contribute to the pathology of
      R-EAE. In addition, the results demonstrate that peptide-specific tolerance
      induction appears to have potential for the treatment of T cell-mediated
      inflammatory diseases.

PMID- 1374099
TI  - Expression of an exogenous tumor necrosis factor (TNF) gene in TNF-sensitive cell
      lines confers resistance to TNF-mediated cell lysis.
AB  - TNF, a cytokine with cytotoxic activity on a variety of tumor cells, is mainly
      produced by macrophages; however, some tumor cell types of non-macrophage origin,
      apparently resistant to TNF-mediated cell lysis, can also produce TNF. It is not
      clear whether these cells were TNF-resistant a priori or whether protective
      mechanisms against toxicity of autocrine TNF may be induced in TNF-producing
      cells. Murine L929sA fibrosarcoma cells, which are highly sensitive to TNF
      cytotoxicity, were transfected with the neomycin resistance (neor) gene, alone or
      in combination with the human (h) or the murine (m) TNF gene. All exogenous genes
      were under control of the constitutive SV40 early promoter. After cotransfection,
      the number of neor colonies was 10 to 100% as compared with the number of
      colonies upon transfection with the neor gene alone. An appreciable fraction of
      these colonies (50-100%) constitutively produced biologically active TNF. mTNF
      producing L929 cells were fully TNF resistant, whereas hTNF-producing cells
      showed partial TNF resistance. Specific TNF binding could not be detected on mTNF
      producing L929sA transfectants, whereas hTNF-producing cells showed reduced TNF
      binding. Apparently, TNF gene expression, even in a priori TNF-sensitive cells,
      can induce mechanisms to prevent toxicity by both autocrine and exogenous TNF. No
      TNF resistance was induced by expression of a gene sequence encoding the 9-kDa
      membrane-bound presequence part of the 26-kDa mTNF proform. Expression of a
      mutant 26-kDa TNF gene coding for a quasi-inactive mature mTNF induced only weak
      TNF resistance as compared with the complete resistance obtained after
      transfection with the wild-type gene. These findings show that the membrane-bound
      TNF presequence as such is not sufficient for induction of TNF resistance and
      imply that the active site of mature TNF is involved in modulation of TNF
      responsiveness upon autocrine TNF production.

PMID- 1374100
TI  - H chain V region sequences of three human monoclonal IgM with anti-myelin
      associated glycoprotein activity.
AB  - The amino acid sequence corresponding to the V region H chain gene used by three
      monoclonal IgM directed to the myelin-associated glycoprotein (MAG) is presented.
      They all belonged to the VHIII variability subgroup, but each may well represent
      a new member of this family inasmuch as their homology with previously sequenced
      VHIII genes was less than 80%. Strikingly, there was no greater homology between
      the H chain V regions of the anti-MAG IgM. Partial amino acid sequence data
      indicated that these V regions were joined to as yet unidentified DH segments;
      however, two H chains used very similar DH, possibly indicating that this
      sequence was involved in the fine specificity of the IgM for MAG. All H chains
      included a JHIV region. These data, together with results obtained from the
      sequence of the three kappa L chains of the same IgM molecules (Mihaesco, E., H.
      Ayadi, N. Congy, M. C. Gendron, J. P. Roy, H. Heyermann, B. Frangione, and J. C.
      Brouet. 1989. J. Biol. Chem. 264:21481), indicate that the repertoire of VL and
      VH gene segments used by anti-MAG IgM is quite diverse, in contrast to previous
      structural data obtained for other human monoclonal IgM autoantibodies. Possibly,
      these differences reflect distinct pathogenesis.

PMID- 1374101
TI  - Murine common acute lymphoblastic leukemia antigen (CD10 neutral endopeptidase
      24.11). Molecular characterization, chromosomal localization, and modeling of the
      active site.
AB  - To further analyze CD10/NEP function in lymphoid and nonlymphoid cells using well
      characterized murine systems, we isolated the murine CD10/NEP homologue,
      determined its chromosomal location, and modeled the enzyme's active site. The
      murine CD10/NEP cDNA predicts a 750-amino acid (aa) type II integral membrane
      protein with 90% identity to the human CD10 sequence and 100% conservation of
      critical aa and functional motifs. The latter include the pentapeptide consensus
      sequence required for zinc binding and catalytic activity, additional aa
      associated with substrate binding, and the extracellular cysteines that
      participate in disulfide bonds required for enzymatic activity. Like its human
      homologue, murine CD10/NEP has multiple alternative 5'-untranslated region
      sequences. The gene is localized on the proximal half of murine chromosome 3. In
      Northern analysis, murine CD10/NEP transcripts are abundant in bone marrow
      stromal cells that support pre-B cell differentiation but are undetectable in
      representative Abelson transformed pre-B cell lines. The murine CD10/NEP active
      site was modeled by aligning critical conserved CD10/NEP residues with comparable
      residues in the active site of thermolysin, a bacterial metalloprotease with
      similar substrate specificity. The model predicts that the two enzymes have
      similar clefts that comprise the active site and permit zinc-dependent substrate
      interactions.

PMID- 1374102
TI  - Prostaglandin E2 and other cyclic AMP-elevating agents modulate IL-2 and IL-2R
      alpha gene expression at multiple levels.
AB  - cAMP is an intracellular second messenger that conveys inhibitory signals for T
      cell activation and clonal proliferation. cAMP also inhibits the production of IL
      2 and IL-2R alpha-chain expression. To determine the mechanisms of this
      inhibition, human peripheral blood T lymphocytes were stimulated with anti-CD3
      mAb, PHA, PMA, or ionomycin, alone or in combination. cAMP elevation by PGE2,
      cholera toxin, or the cell-permeable analogue 8-bromo-cAMP inhibited the tyrosine
      phosphorylation of a protein of 100 kDa. This inhibition was associated with
      decreased IL-2 production and IL-2R alpha expression at both the protein product
      and the mRNA levels. Nuclear run-off assays showed that the inhibitory effect of
      cAMP on IL-2 and IL-2R alpha gene expression is mediated at the transcriptional
      level. H-8, an inhibitor of protein kinase A, reversed the inhibitory effect of
      cAMP on nuclear transcription of the IL-2 gene, suggesting that this is mediated
      through activation of protein kinase A. Post-transcriptionally, cAMP elevation
      decreased the t1/2 of IL-2 mRNA by more than 50%. These data indicate that cAMP
      inhibits cell membrane, cytoplasmic, and nuclear events associated with T cell
      activation and highlight the complexities of its action of lymphocyte function.

PMID- 1374103
TI  - IFN-gamma-producing ability as a possible marker for the protective T cells
      against Mycobacterium bovis BCG in mice.
AB  - We searched for a functional marker with which T cells mediating acquired
      cellular resistance (ACR) can be discriminated from those mediating delayed-type
      hypersensitivity (DTH) in mice immunized with Mycobacterium bovis BCG. Four wk
      after injection of the mice with 10(5) viable BCG (vBCG) cells emulsified in IFA,
      a passive transfer experiment revealed that T cells mediating DTH as well as ACR,
      which we designated TACR, were generated in the spleen. In contrast, T cells
      mediating only DTH (TDTH) were generated by immunization with 10(7) killed BCG
      cells along with IFA. The transferring ability of both TACR and TDTH was
      substantially reduced by treatment with anti-Thy-1.2 or anti-CD4 mAb plus
      complement, whereas anti-CD8 treatment had no effect. To determine the functional
      differences between TACR and TDTH, we assessed IL-2 and IFN-gamma production from
      TACR and TDTH after stimulation with PPD in vitro. Similar levels of enhanced IL
      2 activity were detected in the culture supernatants of both groups of T cells.
      However, augmented production of IFN-gamma was observed only in TACR. This
      finding was confirmed by Northern blot analysis for detection of IFN-gamma
      specific mRNA. In addition, a significant increase in the number of IFN-gamma
      producing cells was observed only in T cells from mice immunized with vBCG. The
      production of IFN-gamma was also totally abolished by treatment with anti-Thy-1.2
      and anti-CD4 mAb plus complement in vitro, whereas anti-CD8 mAb treatment had no
      effect. These results suggest that CD4+ protective T cells generated by
      immunization with vBCG are characterized by the ability to produce IFN-gamma
      after stimulation with specific Ag.

PMID- 1374104
TI  - Expression of c-kit by mesenteric lymph node cells from Nippostrongylus
      brasiliensis-infected mice and by mast cell colonies developing from these cells
      in response to 3T3 fibroblast-conditioned medium.
AB  - Mast cell committed progenitors are nongranulated cells found in mesenteric lymph
      nodes of mice infected with Nippostrongylus brasiliensis (Nb-MLN) but not from
      normal mice. Mast cell committed progenitors can respond to either IL-3 or to a
      factor(s) present in 3T3 fibroblast conditioned media (F-CM) by formation of mast
      cell colonies. Previous studies from ours and other laboratories suggested that
      mast cell differentiation involved the W allele product, c-kit, as a receptor and
      Sl allele product, stem cell factor, as a growth factor. We report here that Nb
      MLN cells, which can respond to F-CM by mast cell colony formation, also contain
      cells that express message for c-kit, and that c-kit message cannot be detected
      in naive mesenteric lymph node cells, which cannot respond to F-CM. Antisense
      oligonucleotides to c-kit inhibit mast cell colony formation by Nb-MLN cells in
      response to F-CM, but not to conditioned medium of PWM-stimulated spleen cells as
      a source of IL-3. The antisense oligonucleotides also inhibit the degree of
      granulation by mast cells derived from culture. The results suggest that c-kit
      and its ligand, stem cell factor, are necessary for mast cell-committed
      progenitors to proliferate and granulate in response to F-CM but not IL-3.

PMID- 1374105
TI  - Regulation of lymphokine-activated killer cell induction by human recombinant IL
      1 receptor antagonist. Obligate paracrine pathway of IL-1 during lymphokine
      activated killer cell induction.
AB  - IL-2-stimulated human lymphocytes, referred to as lymphokine-activated killer
      (LAK) cells, can develop a broad range of lytic activity against fresh tumor
      cells and cultured tumor cell lines. IL-1, a pleiotropic cytokine shown to
      synergize with IL-2 on LAK induction, is endogenously synthesized and secreted by
      LAK cells. Immunoblot analysis demonstrated that IL-2-stimulated PBL produced the
      31- to 34-kDa pro-molecules of IL-1 within 24 h and maintained their expression
      for at least 96 h. The role of secreted IL-1 has been examined using rIL-1R
      antagonist (IL-1ra). The addition of IL-1ra to LAK activation culture resulted in
      dose-dependent inhibited lytic activity, which was more apparent in LAK cells
      cultured with higher doses of IL-2. However, IL-1ra had no effect on
      proliferative responses elicited in LAK cells by IL-2. Moreover, when IL-1
      binding was blocked by IL-1ra, the expression of the IL-2R p55 subunit was
      reduced compared with control LAK cells. The effect of IL-1 binding blockade on
      expression of other cytokine mRNA was further examined by polymerase chain
      reaction analysis, and, specifically, inhibition of both TNF-alpha and TNF-beta
      mRNA expression by IL-1ra was observed in PBL stimulated with IL-2. The reduced
      biologic activity of TNF in culture supernatants correlated well with the
      inhibition of mRNA expression. These findings suggest that autocrine/paracrine IL
      1 is involved in the initial generation of LAK activity and, in particular, that
      TNF expression could be induced via an IL-1 autocrine pathway.

PMID- 1374106
TI  - Expansion of murine T cells bearing a unique T cell receptor beta-chain in Friend
      virus-induced tumor in situ.
AB  - Heterogeneity of V alpha 1+ and V beta 10+ TCR alpha beta-chains, which are
      predominantly used in anti-FBL-3 CTL clones established in vitro, was
      investigated at a nucleotide level in FBL-3 tumor-infiltrating lymphocytes (TIL)
      in vivo. The majority (90%) of V beta 10+ beta-chains dominated in TIL used
      homogeneous V beta 10D beta 2.1 sequences identical to that used in the T cell
      clones with cytotoxic functions. The homogeneous TCR beta-chain expression was
      dominant and found to be about 10% of the total TCR beta-chains in the TIL
      population, which was a greater than 300-to 900-fold increase than in the
      regional lymph nodes. This is in good agreement with the in vitro data showing
      that about 11% CTL clones used the homogeneous V beta 10D beta 2.1+ beta-chain.
      However, the J beta segment does not seem to contribute greatly to the
      recognition and selection of this TCR because some of homogeneous VD+ beta-chains
      were associated with J beta segments other than J beta 2.7 of the CTL clones. The
      frequency of the V alpha 1J alpha 112-2+ alpha-chain expression of the CTL type
      was much less (3- to 80-fold increase compared to that of lymph node) and also
      varied in sample materials, indicating the lower contribution of the alpha-chain
      for the oligoclonality of the TCR. The results were also confirmed by
      quantitative PCR and RNase protection assays. This suggests that the dominant
      expression of the homogeneous TCR beta-chain is due to the expansion of the
      particular anti-FBL-3 CTL in the tumor in situ. Also, the TCR beta-chain,
      especially the V beta D beta region, rather than alpha-chain is more important
      for the recognition and selection of the anti-FBL-3 TIL with cytotoxic functions.

PMID- 1374107
TI  - Genes for the trophoblast interferons in sheep, goat, and musk ox and
      distribution of related genes among mammals.
AB  - The trophoblast interferons (IFNs) are a family of Type 1 IFN found in domestic
      ruminants that are most closely related to the little-studied 172-amino-acid IFN
      omega. They are produced in massive amounts by the preimplantation conceptus at a
      time coincident with maternal recognition of pregnancy, and are implicated in
      playing an important role in this process. Here we report the characterization of
      four distinct members of the ovine trophoblast IFN (oTP-1) gene family, and
      demonstrate that they, along with previously characterized bovine trophoblast
      (bTP-1) genes, possess distinctive promoter sequences when compared to ovine and
      bovine IFN-omega genes. Genomic Southern blot analysis of numerous mammalian
      species (zoo blots) indicate that, whereas the IFN-omega are widely distributed
      among mammals, genes for the trophoblast IFN appear to be limited to ruminant
      species within the Artiodactyla order. Further polymerase chain reaction (PCR)
      analysis of trophoblast IFN genes in these ruminant species has permitted
      isolation of genes for goat and musk ox trophoblast IFN. These data suggest that
      the trophoblast IFNs are a distinct family of IFN with a limited distribution
      among mammals.

PMID- 1374108
TI  - Interferon-gamma receptor: mRNA half-life, receptor mass, and abundance on A431
      human epidermoid carcinoma cells.
AB  - The human interferon-gamma (IFN-gamma) receptor protein and mRNA were identified
      in the epidermoid carcinoma cell line A431 by radioligand binding and Northern
      hybridization, respectively. Receptor affinity and receptor number per cell were
      calculated by Scatchard analysis of saturation binding data. The half-life of the
      receptor mRNA was determined by actinomycin D inhibition of de novo
      transcription. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) analysis of covalently cross-linked 32P-labeled IFN-gamma and its receptor
      is consistent with a molecular mass of approximately 99 kD. Radioligand binding
      analysis revealed 27,000 high affinity (KD = 7.1 x 10(-10) M) receptors per cell.
      Northern hybridization using an IFN-gamma receptor cDNA probe revealed a single
      mRNA of 2.2 kb. The receptor mRNA half-life in actinomycin D-treated cells was
      4.7 h.

PMID- 1374109
TI  - Specific interferon genes are expressed in individual cells in the peritoneum and
      bone marrow of normal mice.
AB  - The use of a highly sensitive method of in situ hybridization capable of
      detecting one copy of IFN mRNA per cell showed that from 20-50% of the cells from
      the peritoneum and bone marrow of both normal pathogen-free and axenic mice
      exhibited grain counts significantly greater than background levels following
      hybridization with riboprobes specific for the mouse interferon-alpha (IFN
      alpha), IFN-beta, or IFN-gamma genes. Labeling was shown to be specific, as the
      labeled probe was displaced by a 200-fold excess of the specific unlabeled probe
      but not by a 200-fold excess of an unrelated probe. Grain counts were reduced to
      background levels when cells were pretreated with ribonuclease prior to in situ
      hybridization. The extent of labeling with either IFN-alpha or IFN-beta-specific
      probes increased following i.v. inoculation of mice with the IFN-inducer
      Newcastle disease virus (NDV) whereas the degree of labeling observed with a
      probe specific for beta-actin remained unchanged. No significant differences were
      observed in the number of bone marrow or peritoneal cells that expressed IFN
      alpha or IFN-beta mRNA from either high (C57B1/6) or low (BALB/c) IFN-producing
      strains of mice. The majority of IFN-alpha and IFN-beta-containing cells from
      both the bone marrow and peritoneum of normal pathogen-free and axenic mice
      resembled monocytes morphologically, whereas the majority of IFN-gamma mRNA
      containing cells resembled small lymphocytes. In addition, in the bone marrow a
      number of large cells which resembled megacaryocytes were found to express high
      levels of IFN-alpha mRNA. Nuclear run-on assays showed that IFN-alpha and IFN
      beta genes were actively transcribed in both bone marrow and peritoneal cells
      from normal and axenic mice. Low levels of de novo IFN-gamma RNA synthesis were
      detected in the nuclei of peritoneal cells only. The expression of IFN genes in
      individual cells in the tissues of normal animals may constitute a basis for the
      regulation of both homeostasis and host defense against virus infection and
      neoplastic cells.

PMID- 1374110
TI  - The shape of DNA elution dose-response curves under non-denaturing conditions:
      the contribution of the degree of chromatin condensation.
AB  - We have re-examined the effect of detergent type, pH and temperature of lysis on
      the shape of the DNA elution dose response under non-denaturing conditions using
      plateau-phase CHO cells. Results practically identical to those previously
      published (Okayasu and Iliakis, 1989) were obtained, with a 1 h incubation at 60
      degrees C during lysis with sodium-N-laurylsarcosine (NLS) resulting in almost
      linear dose-response curves. We also examined chromatin decondensation as a
      contributing factor in the linearization observed in the elution dose-response
      curve under the above conditions. When nuclei with condensed chromatin were
      prepared from irradiated cells, applied on the filter and lysed with NLS at room
      temperature, a shoulder-type elution dose-response curve was obtained only
      slightly higher than that of cells lysed under the same conditions. However, when
      nuclei prepared from irradiated cells were applied on the filter after relaxation
      of chromatin by incubation in low ionic strength buffer and lysed with NLS at
      room temperature, an almost linear dose-response curve was obtained similar to
      that of cells lysed with NLS at 60 degrees C. Lysis with NLS at 60 degrees C of
      nuclei with relaxed chromatin did not further modify the DNA elution dose
      response curve. Based on these results we propose that the linearization of the
      DNA elution dose-response curve observed after chromatin decondensation reflects
      a reduction in the degree of chromatin compactness in the nuclear complexes that
      leads to a relatively uniform distribution of the DNA on the filter and reduces
      trapping of elutable material in the compact nuclear structures otherwise
      present. Since high radiation doses dissolve compact nuclear structures, trapping
      of elutable material is expected to be highest at low doses of radiation, leading
      to the observed reduction in the fraction of DNA eluted per Gy at low versus high
      radiation doses and thus to the observed shoulder. Furthermore, we propose that
      the linearization of the DNA elution dose-response curves observed in cells lysed
      in NLS at 60 degrees C may also be due to a decondensation of the nuclear
      complexes on the filter as a result of the combined action of detergent and high
      temperature. The notion of a correlation between DNA elution dose response and
      cell radiosensitivity was examined in two human (SQ20B, SCC61) and two Chinese
      hamster (V-79, irs-2) cell lines with widely different
      radiosensitivities.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374111
TI  - Nuclear area measurement on viable cells, using confocal microscopy.
AB  - We describe a rapid procedure for the accurate measurements of nuclear areas on
      unperturbed living cells as used in radiobiological experiments, using the
      confocal laser scanning microscope. The microdosimetric interpretation of
      radiobiological data requires precise information on the nuclear area of cells as
      irradiated with high-LET radiation.

PMID- 1374112
TI  - DNA ligands as radioprotectors: molecular studies with Hoechst 33342 and Hoechst
      33258.

PMID- 1374113
TI  - Humoral immune responses in human HIV-1 infection clearance of initial burst of
      virus replication and protection against disease progression.
AB  - An attempt is made to summarize the evidence that humoral immune responses in
      natural HIV-1 infection play a role in clearance of the initial burst of
      replication as well as in protection against rapid disease progression.
      Therefore, the so-called "asymptomatic carrier state" was defined on the basis of
      immunological characteristics, such as CD4+ cell number, CD45RA-CD29+ cell
      number, CD4+ proliferative responses to anti-CD3 mAbs and soluble activation
      markers, as well as virological characteristics such as the state of the viral
      genome in the cell, levels of genomic RNA production, antigenemia, viremia and
      virus phenotype. During natural infection two major classes HIV-1 neutralizing
      and cell-fusion inhibiting antibodies are elicited. One population directed
      against mostly continuous epitopes localized in the third variable domain (V3) of
      the envelope and one against discontinuous epitopes of the envelope. The last
      population blocks gp120-CD4 attachment, the first does not. The role of each of
      these populations of functional antibodies, in the clearance of viremia and the
      maintenance of the asymptomatic carrier state is discussed.

PMID- 1374114
TI  - Prognostic assessment of fulminant hepatitis from indication criteria for liver
      transplantation.
AB  - The clinical outcome in 15 patients with fulminant hepatitis was predicted by the
      indication criteria for liver transplantation used in five different
      transplantation centers. Fifty-four to 100% of 13 fulminant hepatitis patients
      died who were fulfilled with these criteria for transplantation. Most of the
      patients died within five to nine days after the decision of liver
      transplantation was made. Takahashi's score of prognostic assessment for
      fulminant hepatitis decreased rapidly during the time when all the different
      criteria in transplantation centers were fulfilled. However, two survival cases
      with the acute type of fulminant hepatitis were incorrectly judged to be
      transplanted by the two criteria. The Cambridge's criterion for liver
      transplantation predicted the prognosis of fulminant hepatitis most correctly;
      sensitivity was 84.6% and specificity 100%.

PMID- 1374115
TI  - A tau-related protein of 130 kDa is present in Alzheimer brain.
AB  - Two abnormal entities of 69 and 130 kDa, immunologically related to the
      microtubule-associated tau proteins, are present in the hippocampus and the
      frontal cortex of the Alzheimer brain, which contain a large number of
      neurofibrillary tangles (NFTs), but are absent in the cerebellum, which does not
      contain these structures. Epitope mapping with antibodies spanning domains
      present in the N-terminal, middle, and C-terminal tau sequence demonstrated that
      the 69- and 130-kDa entities belong to the tau family. Both the 69- and the 130
      kDa proteins were found in an insoluble form and were the major tau species
      present in purified NFTs. A procedure was devised that allowed us to prepare from
      Alzheimer hippocampi two NFT fractions differing in size (20 and 3 microns), both
      of which contained the tau entities of 130 and 69 kDa.

PMID- 1374116
TI  - Characterisation of an allosteric modulatory protein associated with alpha
      [3H]amino-3-hydroxy-5-methylisoxazolepropionate binding sites in chick
      telencephalon: effects of high-energy radiation and detergent solubilisation.
AB  - alpha-[3H]Amino-3-hydroxy-5-methylisoxazolepropionate ([3H]AMPA) binds to 1-day
      old chick telencephalon membranes with KD and Bmax values of 138 nM and 2.56
      pmol/mg of protein, respectively. High-energy radiation bombardment of intact
      frozen telencephalon resulted in a biphasic inactivation curve for [3H]AMPA
      binding. At a 5.8-Mrad radiation dose, the affinity of [3H]AMPA binding was
      increased (54 nM), but there was no apparent alteration in the Bmax value (2.76
      pmol/mg of protein). We attribute this phenomenon to the inactivation of a high
      molecular weight modulatory protein that down-regulates the affinity of [3H]AMPA
      binding. The estimated molecular masses of the AMPA binding site and of the
      modulatory component were 59 and 108 kDa, respectively. Solubilisation with n
      octyl-beta-glucopyranoside resulted in an increase in the Bmax (4.7 pmol/mg of
      protein) with no pronounced alteration in the affinity (109 nM) of [3H]AMPA
      binding. However, the solubilisation-induced increase in Bmax did not occur in
      telencephalon irradiated before solubilisation. In contrast, the increase in
      affinity induced by radiation treatment was still detected in solubilised
      extracts. These results suggest that the number and affinity of [3H]AMPA sites in
      chick telencephalon are closely regulated and that the modulatory systems
      involved are affected by both irradiation and solubilisation.

PMID- 1374117
TI  - Actin depolymerizing factor is a component of slow axonal transport.
AB  - We examined the low molecular weight proteins transported with actin in the
      chicken sciatic nerve after injection of [35S]methionine into the lumbar spinal
      cord. A prominent component of slow axonal transport with apparent molecular mass
      19 kDa comigrated on two-dimensional gels with chicken actin depolymerizing
      factor (ADF), previously shown to be a major actin-binding protein in brain.
      There was comparatively little radioactivity associated with the actin monomer
      sequestering proteins, profilin or cofilin, and examination of the rapid
      component of axonal transport failed to reveal appreciable quantities of actin,
      ADF, profilin, or cofilin. These results show that both actin and ADF are carried
      by slow axonal transport and raise the possibility that actin travels within the
      axon in an unpolymerized form in a complex with ADF.

PMID- 1374118
TI  - A dihydropyridine-resistant component in the rat adrenal secretory response to
      splanchnic nerve stimulation.
AB  - A study of the effects of dihydropyridine Ca2+ channel modulators on the release
      of catecholamines from perfused rat adrenal glands, evoked by electrical
      stimulation of their splanchnic nerves, is presented. Electrically mediated
      secretory responses were compared to chemically mediated responses (exogenous
      acetylcholine, nicotine, or high K+). Intensities of stimuli were selected to
      produce quantitatively similar secretory responses (between 100 and 200 ng per
      stimulus). The main finding of the study is that responses to transmural
      stimulation (300 pulses at 1 or 10 Hz) and to acetylcholine were inhibited only
      partially (about 50%) by isradipine, an L-type Ca2+ channel blocker. In contrast,
      responses to high K+ (17.5 mM for 2 min) were highly sensitive to isradipine
      (IC50 = 8.2 nM). Responses to nicotine were also fully inhibited by this drug.
      Bay K 8644 (an L-type Ca2+ channel activator) potentiated mildly the secretory
      responses to electrical stimulation at 10 Hz and to acetylcholine, but increased
      threefold the responses to K+ and nicotine. It is, therefore, likely that
      responses mediated by high K+ or nicotinic receptors are triggered by external
      Ca2+ gaining access to the internal secretory machinery through L-type,
      dihydropyridine-sensitive voltage-dependent Ca2+ channels. However, in addition
      to nicotinic receptors, the physiological stimulation of adrenal medulla
      chromaffin cells through splanchnic nerves has other components, i.e., muscarinic
      receptor stimulation or the release of cotransmitters such as vasoactive
      intestinal polypeptide. The poorer sensitivity to dihydropyridines of secretory
      responses triggered by electrical stimulation of splanchnic nerve terminals or
      exogenous acetylcholine speaks in favor of alternative Ca2+ pathways, probably
      some dihydropyridine-resistant Ca2+ channels, in modulating the physiological
      adrenal catecholamine secretory process.

PMID- 1374119
TI  - Selective expression of DM-20, an alternatively spliced myelin proteolipid
      protein gene product, in developing nervous system and in nonglial cells.
AB  - Mutations within the gene for myelin proteolipid protein (PLP), a major myelin
      structural protein, result in abnormal glial differentiation, suggesting that the
      PLP gene products play some other functional roles. Transcripts from the PLP gene
      were analyzed in the developing mouse brain by a sensitive method using
      polymerase chain reaction. The mRNA for DM-20, an alternatively spliced
      transcript from the PLP gene, was detected in the embryonic mouse brain as early
      as embryonic day 11, long before the appearance of oligodendrocytes, which were
      considered to be responsible for PLP production. PLP gene expression was analyzed
      in various cell lines to determine whether synthesis of the DM-20 mRNA is
      restricted to those of glial cell lineage. All of the nervous system cell lines
      examined, including nonglial cell lines, produced DM-20 mRNA but no or very
      little PLP mRNA. Peripheral sciatic nerve from adult Wistar rats also produced
      mainly DM-20 mRNA. These results indicate that DM-20 is not only a myelin
      structural protein, but it also plays other roles in the nervous system that seem
      to relate, at least in part, to glial differentiation.

PMID- 1374120
TI  - The NK-1 receptor and a calcium-phospholipid pathway: inositol trisphosphate
      production and calcium movements induced by selective agonists of neurokinin
      receptors in rat parotid glands.
AB  - In the rat parotid gland, substance P has been shown to induce a
      phosphatidylinositol bisphosphate breakdown resulting in an inositol
      trisphosphate production. These data suggested that substance P activated a
      phospholipase C and thus mediated its effects through the calcium-phospholipid
      pathway. To determine which neurokinin (NK) receptor was involved in the
      substance P response, we have used selective agonists of the different NK
      receptors and examined their effects on both inositol trisphosphate production
      and calcium movements. A selective NK-1 receptor agonist, [Sar9Met(O2)11]
      substance P, evoked an [3H]inositol trisphosphate production and a rapid and
      transient 45Ca2+ efflux. On the other hand, selective NK-2 and NK-3 receptor
      agonists, [beta-Ala8]-NKA(4-10) and [MePhe7]-NKB, respectively, were without
      effect. We conclude that, in the rat parotid glands, only the NK-1 receptors are
      coupled to the calcium-phospholipid pathway. The C-terminal part of substance P
      appeared to be sufficient to stimulate this route because the C-terminal
      octapeptide, substance P(4-11), mimicked substance P effects on both inositol
      trisphosphate production and calcium movements. The NK-2 and NK-3 receptors, if
      present in the rat parotid glands, are not associated with the calcium
      phospholipid pathway.

PMID- 1374121
TI  - Autologous facial fat transplantation: improved graft maintenance by microbead
      bioactivation.
AB  - An alternative approach to the management of free fat transplantation resorption
      was evaluated in a rat facial model. Fat grafts obtained from the inguinal region
      were transferred to subcutaneous lateral facial sites in 20 animals. The grafts
      were mixed with either basic fibroblast growth factor (bFGF) alone or dextran
      beads that had been pretreated with bFGF. The grafts were then compared by weight
      and histology at 1 and 6 months postoperatively. Although graft weights were
      nearly comparable at 1 month, substantial differences were seen at 6 months, with
      the bead-containing grafts exhibiting near complete weight maintenance and better
      overall graft form. Histologically, the bead-containing grafts had extensive
      intercellular collagen formation and a heterogeneity of adipocyte cell sizes,
      particularly after 1 month. These findings suggest that the addition of cell
      specific bioactive peptides that affect either the preadipocyte cell line and/or
      the fibroblastic components of the recipient site improve postoperative fat graft
      weight maintenance. Delivery of the biochemical agent appears to require a
      carrier system to exert its effects.

PMID- 1374122
TI  - Primary mucoepidermoid carcinoma of an intraparotid lymph node.

PMID- 1374123
TI  - Macroamylasemia in a 5-year-old girl.
AB  - In macroamylasemia, a macromolecular complex consisting of amylase linked to
      immunoglobulins circulates in the plasma and usually causes benign
      hyperamylasemia with low or normal amylasuria. Macroamylasemia is extremely rare
      in pediatric patients as it has been described in only four patients. We report
      herein the case of a 5-year-old girl with abdominal pain and macroamylasemia. To
      recognize macroamylase, we used agar gel electrophoresis, PEG precipitation, and
      fast protein liquid chromatography (FPLC). In our case, FPLC was found to be the
      most reliable method for the identification of the macromolecular complex.
      Macroamylasemia is merely a biochemical abnormality that is not associated with
      any kind of pathology. Its identification is therefore essential in order to
      avoid a wrong diagnosis, i.e., pancreatitis, with consequent inappropriate
      therapies.

PMID- 1374124
TI  - Intestinal uptake and transmission of macromolecules into the blood in the young
      guinea pig.
AB  - The developmental changes in the ability of the small intestinal epithelium to
      take up and transfer into blood the macromolecules bovine serum albumin (BSA),
      bovine immunoglobulin G (BIgG), and fluorescein isothiocyanate-labeled dextran
      70,000 (FITC-dextran) were studied in guinea pigs 0-14 days of age. In addition,
      in the same animals, the activities of the proteases cathepsin B and D within the
      intestinal mucosa were measured. Four hours after gavage feeding, 0-day-old
      guinea pigs showed an uptake of the markers into the enterocytes throughout the
      small intestine. In 2-day-old guinea pigs, the markers were only detected in the
      enterocytes in the distal part. All three macromolecules passed into the blood in
      these young animals. In 7-day-old guinea pigs, no epithelial marker uptake was
      observed, but low levels of BSA and FITC-dextran could still be detected in
      serum. Neither epithelial uptake nor transfer of the markers to the blood could
      be found in the animals that were 14 days of age. The activity of cathepsin B and
      D in the intestinal mucosa showed a tendency to increase with age, and for all
      ages the activity in the distal part was higher than in the proximal part. The
      results showed that the small intestine in guinea pigs at birth is capable of
      macromolecular uptake and transfer into the circulation. This ability decreased
      with age eventually leading to intestinal closure after 1 week. The histological
      findings implied that intestinal closure was a consequence of a replacement of
      fetal absorptive cells with adult cells lacking this ability.

PMID- 1374125
TI  - Infantile refsum disease: gastrointestinal presentation of a peroxisomal
      disorder.
AB  - This article describes two siblings with infantile Refsum disease (IRD) whose
      initial presentation was that of malabsorption and mimicked a-beta- or homozygous
      hypo-beta-lipoproteinemia. Failure to recognize IRD in the first-born child
      precluded proper genetic counseling and prenatal diagnosis in subsequent
      pregnancies and also caused considerable delay in diagnosing IRD in the second
      child. The clinical heterogeneity of peroxisomal disorders constitutes a
      diagnostic challenge, which demands a high degree of awareness from the part of
      the clinician. This is particularly the case with IRD, where protracted diarrhea
      with low serum cholesterol levels appears to be a frequently occurring initial
      feature during the 1st months of life.

PMID- 1374127
TI  - Changes in brain serotonergic activity during hierarchic behavior in Arctic charr
      (Salvelinus alpinus L.) are socially induced.
AB  - The experiment was performed in two phases. During the first phase (phase 1) the
      dominance hierarchy was determined in 4 groups of Arctic charr (Salvelinus
      alpinus L.), each group consisting of 4 fish. Phase 2 was started by rearranging
      phase 1 fish into 4 new groups. Group 1 consisted of previously dominant fish and
      groups 2, 3 and 4 of fish that previously held rank 2, 3 and 4, respectively.
      After phase 2 telencephalon and brain stem were analyzed with regard to their
      contents of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid
      (5-HIAA), the principle metabolite of 5-HT. No correlation was found between the
      social rank (measured as dominance index) during phase 1 and the brain
      serotonergic activity (measured as the ratio 5-HIAA/5-HT) determined after phase
      2. However, most important, the 5-HIAA/5-HT ratio was significantly correlated
      with the last experienced social rank, i.e. that acquired during phase 2. These
      results shows that the difference in brain serotonergic activity between dominant
      and subordinate fish develops through social interactions. Further, we found that
      previous subordinate experience inhibited aggressive behavior, an effect which,
      in the light of available information on stress and 5-HT, could be related to the
      increase in brain serotonergic activity. We hypothesize that stress induces an
      increased serotonergic activity which in turn inhibits the neuronal circuitry
      which mediates aggressive behavior.

PMID- 1374126
TI  - The apical border plaque in chronic adult periodontitis. An ultrastructural
      study. II. Adhesion, matrix, and carbohydrate metabolism.
AB  - THE AIM OF THIS STUDY was to characterize the plaque matrix and relevant aspects
      of metabolism of the apical border plaque in relation to teeth affected by
      chronic adult periodontitis. The material comprised 56 teeth from 24 patients.
      Ruthenium red, alcian blue, lanthanum nitrate, and safranin 0 were used to label
      matrix polyanionic macromolecules and periodic acid-thiosemicarbazide-silver
      proteinate for intracellular polysaccharide (IPS). The matrix components were
      amorphous, fibrillar, or globular. Many intact bacteria exhibited extracellular
      polysaccharides or glycocalyces associated with their cell wall and cytoplasmic
      IPS granules. The latter varied in size and distribution and were evident even in
      the most apically-advanced intact microorganisms. The results indicate that the
      matrix and IPS features of the apical border plaque in chronic periodontitis in
      certain respects resemble those of subcontact area plaque on children's teeth,
      associated with chronic gingivitis and approximal caries. They also suggest the
      establishment of acidic regions in the microniches of the periodontal pocket.

PMID- 1374128
TI  - Researchers get creative in solving MoAb problems.

PMID- 1374129
TI  - Structure and expression of proteolipid protein in the peripheral nervous system.
AB  - Proteolipid protein (PLP), the major myelin protein in the central nervous system
      (CNS), is also made by Schwann cells (SC) in the peripheral nervous system (PNS)
      but is not incorporated into the SC myelin sheath. We analyzed several PLP cDNA
      clones isolated from a rat sciatic nerve cDNA library and found that their coding
      sequences were identical to PLP cDNAs previously isolated from the CNS. In
      addition, we have discovered an unusual form of PLP message, present in both
      brain and sciatic nerve RNA, that is likely formed by alternative splicing within
      the 3' untranslated region of the primary PLP transcript. The absence of PLP from
      the SC myelin sheath thus cannot be explained by an alteration in its amino acid
      sequence. Steady-state levels of PLP mRNA in SC cultures treated with the cAMP
      analogue dibutyryl cAMP (dBcAMP) were not increased, whereas dBcAMP increased
      steady-state levels of mRNA encoding the major myelin protein, P0. We have also
      shown that expression of PLP, unlike that of P0, is regulated in SC in vitro at a
      posttranscriptional level. Finally, the steady-state levels of P0 mRNA are much
      more dramatically reduced than those of PLP mRNA during Wallerian degeneration of
      the peripheral nerve. Thus PLP expression in the PNS is probably controlled by
      different molecular mechanisms from P0, and may not be part of the coordinate
      program of myelin gene expression. In contrast to its expression in the PNS,
      transcription of PLP in the CNS is coordinately regulated along with the other
      myelin protein genes, suggesting there may be differences in the cis-acting
      elements and transacting factors involved in the regulation of PLP transcription
      in SC and oligodendrocytes (OC). Consistent with this notion, we have found that
      most PLP transcripts are initiated at the more proximal of two start sites in the
      PNS, while in the CNS proportionally more PLP transcripts are initiated from the
      distal start site. We propose that the proximal site, utilized predominantly in
      SC, is responsible for maintenance expression of PLP and is not inducible, while
      the distal site is responsible for the rapid, inducible increase of PLP message
      during brain development.

PMID- 1374130
TI  - Platelet-derived growth factor and regulation of Schwann cell proliferation in
      vivo.
AB  - To examine the role of platelet-derived growth factor (PDGF) in the in vivo
      regulation of Schwann cell proliferation, steady-state levels of mRNAs encoding
      PDGF A and B chains, and PDGF alpha and beta receptors were measured in immature
      and adult rat sciatic nerves and in cultured rat Schwann cells. PDGF B chain and
      PDGF beta receptor mRNAs are present in immature rat sciatic nerves and to a
      lesser extent in adult rat nerves. Short-term cultures of neonatal rat Schwann
      cells express PDGF beta receptor mRNA, but not PDGF B chain mRNA, and are
      stimulated to synthesize DNA by addition of PDGF BB to the medium. These data
      indicate that PDGF BB is a developmentally regulated paracrine growth factor for
      rat Schwann cells. Very long-term cultures of rat Schwann cells, which have lost
      normal dependence on exogenous growth factors, express PDGF B chain mRNA as well
      as mRNAs encoding the PDGF alpha and beta receptors, suggesting that, under these
      circumstances, PDGF BB also act as an autocrine growth factor. PDGF A chain mRNA
      is present in both immature and adult rat sciatic nerves and is expressed by
      primary and secondary cultures of rat Schwann cells as well. However, because the
      abundance of PDGF alpha receptor mRNA is very low in rat Schwann cells, PDGF AA
      is not likely to be a significant autocrine growth factor for rat Schwann cells.

PMID- 1374131
TI  - Plasticity of the serotonergic innervation of the dorsal horn of the rat spinal
      cord following neonatal capsaicin treatment.
AB  - Neonatal capsaicin treatments (25 or 50 mg/kg, 12, 24, or 48 hr after birth given
      subcutaneously) were applied in order to follow by immunocytochemical techniques
      the postnatal development and plasticity of the serotonergic system in the dorsal
      horn of the rat spinal cord. Two markers of the lesions of C primary afferents
      induced by capsaicin were tested by immunocytochemical detection: substance P and
      calcitonin gene-related peptide (CGRP). We show that the internal part of
      substantia gelatinosa (lamina Ili) which does not contain serotonergic fibers in
      intact or vehicle-treated rats is invaded within a few days after capsaicin
      treatment by serotonergic fibers apparently sprouting from the deepest laminae.
      Moreover, these fibers often establish axodendritic synapses while synapses are
      rare in intact animals in the whole dorsal horn. This reorganization is stable
      whatever the dose of capsaicin used or the moment chosen for its injection. On
      the other hand, while lesions of substance P-ergic fibers appeared quite stable,
      partial recovery of CGRP innervation was found after 3 to 6 months, especially
      with the low dose of capsaicin. We discuss the ability of the serotonergic system
      innervating the dorsal cord either to find new targets or to fill vacated sites
      when one of its putative targets is removed.

PMID- 1374133
TI  - Three-dimensional reconstruction of bovine intradural spinal root myelin by
      electron microscope tomography.
AB  - Electron microscope tomography was used to reconstruct three-dimensionally the
      configuration of heavy metal staining in bovine intradural spinal root myelin.
      Samples were fixed with glutaraldehyde, exposed to osmium tetroxide, embedded,
      thin sectioned, and finally stained with uranyl-acetate and lead citrate.
      Reconstructions up to 4.2 nm resolution showed a non-uniform distribution of
      stain in the planes of individual cytoplasmic appositions (major dense lines). In
      each reconstructed major dense line the stain was distributed in striated, well
      defined structures. Those structures appear to be nearly parallel between
      neighboring major dense lines. The distribution of stain in the Schmidt-Lanterman
      cleft did not resemble the distribution of stain in the major dense line;
      however, weak striations were present. Evidence that the striated structures are
      not an artifact due to image calculation is discussed.

PMID- 1374132
TI  - Expression of leucocyte adhesion molecules at the human blood-brain barrier
      (BBB).
AB  - The expression of leucocyte adhesion molecules was studied on cerebral endothelia
      by immunocytochemistry. In peritumoral "normal" brain tissue we found low
      endothelial expression of ICAM1, LFA3, CD44, and CD9, whereas VLA1 was present on
      vessels in high incidence and density. LFA1, CD2, and CR3 were found on
      intraluminal and parenchymal leucocytes, but were absent on brain vessels. In
      brain tumors and inflammatory brain lesions, we observed an up-regulation of
      endothelial ICAM1 and LFA3 expression, whereas other adhesion molecules on
      endothelial cells remained unchanged. Within the brain parenchyma, ICAM1 and LFA3
      were found on astrocytes and tumor cells; on the contrary, LFA1 was expressed on
      microglial cells similar to CR3. CD44 and CD9 showed a diffuse neuropil
      expression in normal and tumoral tissue, whereas VLA1 was not expressed on any
      parenchymal cells. Our data show that multiple different adhesion molecules are
      present on blood-brain barrier endothelium (BBB) under normal conditions and some
      adhesion molecules are up-regulated in brain tumors and under inflammatory
      conditions. The presence of adhesion molecules in the vessel walls as well as on
      parenchymal cells like astrocytes and microglia may guide inflammatory cells into
      and through the brain in the course of immune surveillance and inflammation.

PMID- 1374134
TI  - Deprenyl reduces the death of motoneurons caused by axotomy.
AB  - Deprenyl, a monoamine oxidase B inhibitor, appears to slow the progression of
      neurological deficits in Parkinson's disease and cognitive decline in Alzheimer's
      disease. The mechanisms for the slowing of the diseases are unknown. Deprenyl can
      reduce the death of murine substantia nigra neurons when administered after the
      neurons are damaged in MPTP parkinsonism by increasing the neurons' survival
      after they are damaged, rather than by just protecting the neurons against damage
      by blocking the conversion of MPTP to its active form as was previously thought.
      The death of immature motoneurons after separation from their muscle targets by
      axotomy provides a model for assessing trophically dependent neuronal survival.
      To determine whether deprenyl can alter the survival of neurons other than those
      in the substantia nigra, we examined the survival of rat facial motoneurons after
      axotomy at 14 days of age. Using a combination of immunocytochemistry for choline
      acetyl transferase and Nissl staining, we found that deprenyl treatment (10 mg/kg
      every second day) increased by 2.2 times the number of motoneurons surviving 21
      days after the axotomy. This finding showed that deprenyl treatment can rescue
      neurons other than those in the substantia nigra and can compensate in part for
      the loss of target-derived trophic support caused by axotomy.

PMID- 1374135
TI  - Signet-ring cell carcinoid: a primary hepatic carcinoid tumor with cytoplasmic
      inclusions comprising of aggregates of keratin.
AB  - A case of primary hepatic carcinoid tumor was recently encountered, which was
      argyrophil and showed positive reactions to serotonin, gastrin and pancreatic
      peptide in an immunohistochemical hormonal study. The tumor had unusual
      morphologic features. The neoplastic cells had a signet-ring cell appearance,
      similar to the signet-ring cells normally seen in mucin-producing adenocarcinoma.
      Ultrastructural and immunohistochemical studies revealed the formation of the
      signet-ring cells to have been caused by the presence of cytoplasmic inclusions
      consisting of cytokeratins. Further investigation, using eight monoclonal
      antibodies recognizing cytokeratins of different molecular weights, showed the
      accumulated cytokeratins to be of low and medium molecular weights. The
      morphologic observations in this unusual case of hepatic carcinoid tumor are
      described and reported cases with similar features, for which we propose the term
      "signet-ring cell carcinoid," are reviewed.

PMID- 1374136
TI  - Preparing audiovisual materials: overhead transparencies.

PMID- 1374137
TI  - Tenascin: an extracellular matrix protein involved in morphogenesis of epithelial
      organs.

PMID- 1374138
TI  - Reorganization of basement membrane matrices by cellular traction promotes the
      formation of cellular networks in vitro.
AB  - Vascular endothelial cells that are cultured on layers of gelled basement
      membrane matrix organize rapidly into networks of cords or tubelike structures.
      Although this phenomenon is a potential model for angiogenesis in vivo, we
      questioned whether basement membrane matrix directs the differentiation of
      endothelial cells in a specific manner. In this study, we have examined factors
      that influence the formation of cellular networks in vitro in an attempt to
      define a basic mechanism for this process. We found that endothelial cells,
      fibroblasts, smooth muscle cells, and cells of the murine Leydig cell line TM3
      formed networks on basement membrane matrix in much the same fashion. Light and
      electron microscopy, combined with time-lapse videomicroscopy, revealed that
      cells organized on a tesselated network of aligned basement membrane matrix that
      was generated by tension forces of cellular traction. Cellular elongation and
      progressive motility across the surface of the gel were restricted to tracks of
      aligned matrix and did not occur until the tracks appeared. The formation of
      cellular networks on basement membrane matrix was inhibited by reducing the
      thickness of the matrix, by including native type I collagen in the matrix, or by
      disrupting cytoskeletal microfilaments and microtubules. Cell division was not
      required for network formation. Bovine aortic endothelial cells that formed
      networks did not simultaneously transcribe mRNA for type I collagen, a protein
      synthesized by endothelial cells that form tubes spontaneously in vitro.
      Moreover, levels of mRNA for fibronectin and SPARC (Secreted Protein that is
      Acidic and Rich in Cysteine) in network-forming cells were similar to levels seen
      in endothelial cells that did not form networks. Endothelial cells and TM3 cells
      that were plated on highly malleable gels of native type I collagen also formed
      cords and aligned matrix fibers into linear tracks that resembled those generated
      on basement membrane matrix, although the structures were not as well-defined.
      Our observations suggest that the mechanochemical properties of extracellular
      matrices are able to translate the forces of cellular traction into templates
      that direct the formation of complex cellular patterns.

PMID- 1374139
TI  - Immunohistochemical profile of basement membrane proteins and 72 kilodalton type
      IV collagenase in the implantation placental site. An integrated view.
AB  - An immunohistochemical study was performed to investigate the interactions
      between trophoblast and the extracellular matrix in the implantation site of
      early pregnancies. Two basement membrane-related proteins (type IV collagen and
      laminin), as well as the expression of the 72 kilodalton type IV collagenase,
      were studied with affinity-purified antibodies. human placental lactogen, human
      chorionic gonadotropins, and AE1/AE3 cytokeratins were used to identify the
      different cell populations involved in the implantation process. All types of
      trophoblastic cells, from villous cells to the different types of intermediate
      trophoblast, expressed the 72 kilodalton type IV collagenase. Decidual cells,
      Hofbauer's cells, villous fibroblasts, and amnion were also positive. Laminin and
      type IV collagen were expressed in all basement membranes, including large
      decidual and intermediate trophoblast cells, and the villous stroma. Nitabuch's
      layer, an acellular degradative zone at the site of initial attachment, showed
      positivity for type IV collagen. The extracellular matrix in the implantation
      site seems to be a meshwork of, among other components, laminin and type IV
      collagen, in which the invading trophoblastic cells are embedded. The invasive
      capacity of these cells in vivo may be, at least in part, mediated by their type
      IV collagenolytic activity along with that of the decidual cells, thus regulating
      the permeability of the extracellular matrix.

PMID- 1374140
TI  - Carrier-like behaviour from a static but electrically responsive model pore.
AB  - Because of the low dielectric constant of most proteins and lipids, the electric
      field of an ion passing through a narrow pore is long range and will interact
      with neighbouring ionizable residues of the channel protein. The electrical
      structure of the channel may thus change transiently in response to an ion
      passing through the pore. Model calculations then reveal that the ratio of the
      unidirectional ion fluxes may approach 1 as expected for a carrier or shuttling
      ionophore rather than the Ussing ratio expected for a pore. Saturation behaviour
      also becomes carrier-like. Computer simulation is reported showing a continuous
      variation between pore-like and carrier-like behaviour as the parameters of the
      system are allowed to change smoothly.

PMID- 1374141
TI  - Contribution to the understanding of the etiology of vocal fold cysts: a
      functional and histologic study.
AB  - The etiological theories of vocal fold cysts can be divided into two basic
      groups: those of congenital and acquired cysts. In ongoing practice, the authors
      had noted that the greater number of cysts appeared at the functionally most
      active segment of the vocal folds which, on the other hand, has the least number
      of glands. Also, it had been noted that patients with vocal fold cysts tended to
      have hyperkinetic patterns of voice production. These observations indicated the
      possibility of a functional aspect in the etiology of vocal fold cysts, and
      consideration of such a possibility was the aim of this work. In 37 cases, the
      exact location of the cyst was established. In addition, the muscular activity of
      the phonatory apparatus was estimated, patient self-descriptions with respect to
      talkativeness were taken into account, and histological evaluations were made.
      The cysts were most frequently found in the area of the junction of the anterior
      and middle thirds of the free edge of the vocal fold. Muscular activity during
      speech and phonation was increased in study patients. Sixty-five percent of
      patients had epidermoid cysts and 35% had retention cysts of the vocal fold.
      According to study results, the functional aspect of cyst genesis has a marked
      role in the etiology of vocal fold cysts, which points to the great importance of
      functional care for cyst patients.

PMID- 1374142
TI  - Nd:YAG laser ablation of the prostate as a treatment for benign prostatic
      hypertrophy.
AB  - Many techniques have been used to relieve obstructive symptoms associated with
      benign prostatic hypertrophy. Transurethral resection of the prostate (TURP) with
      an electrocautery loop is the most commonly performed operation to relieve
      bladder neck and urethral obstruction caused by prostatic adenoma. There is
      increased interest in alternative therapies to reduce prostatic size for symptom
      relief in this condition. We describe a technique using the neodymium:YAG
      (Nd:YAG) laser and a 600-microns laser quartz fibre with an attached terminal
      gold-plated metal alloy reflector to provide reliable deep penetration into
      prostatic tissue for prostatic adenoma ablation. We report the first use of this
      technique in three patients with benign prostatic obstruction and one with
      localised adenocarcinoma of the prostate.

PMID- 1374143
TI  - Nd:YAG laser treatment of colorectal malignancies: an experience of 4 1/2 years.
AB  - Between 1985 and 1990, 517 patients were treated for colorectal malignancies at
      our department of surgery. Nd:YAG laser therapy was used in 37 cases (7.1%). The
      mean age of these 22 men and 15 women was 71.4 years (range: 22-96 years). One
      hundred-twenty-nine Nd:YAG laser treatments were performed. Indications for laser
      treatment were (1) palliative tumor reduction (n = 21), (2) preresectional laser
      recanalization for obstructing carcinoma (n = 6), and (3) curative treatment (n =
      10). Laser related complications included one perforation of the rectum and one
      rectovaginal fistula. One fatal pulmonary embolism occurred. After palliative
      treatment, five patients died because of tumor progression (mean survival time:
      16 months), two because of other reasons. All patients with obstructing tumors
      could be recanalized successfully. After curative treatment, eight patients are
      still alive without tumor recurrence (mean survival time: 25.5 months), and two
      died of other causes. Palliative Nd:YAG laser treatment of colorectal
      malignancies is a competitive alternative to conventional surgery. Recanalization
      of obstructing tumors is an excellent treatment for large bowel obstruction,
      making one-stage resections possible. Curative treatment should be reserved for
      special cases only.

PMID- 1374144
TI  - Functional changes in vascular smooth muscle and endothelium of arteries during
      diabetes mellitus.
AB  - To investigate the influence of diabetes mellitus on the responsiveness of the
      vascular smooth muscle, the effects of various vasoactive agents on the
      reactivity of the vascular smooth muscle from diabetic animals have been
      undertaken, focusing on the functional changes in the endothelium, alpha
      adrenoceptors, beta-adrenoceptors, voltage-dependent Ca(2+)-channels, receptor
      operated Ca(2+)-channels, phosphatidylinositol turnover and potassium channels.
      Among the functional changes, it is a common phenomenon that decreases in
      acetylcholine-induced production of cyclic GMP are due to the attenuation of
      release of endothelium-derived relaxing factor through an impairment of
      endothelium; this observation was found in both rats and rabbits with diabetes
      mellitus. These functional changes in diabetes may be responsible for the
      vascular complications such as coronary heart disease, cerebrovascular disease,
      and an acceleration in atherosclerosis.

PMID- 1374145
TI  - Antiretroviral activity of mechanism-based irreversible inhibitors of S
      adenosylhomocysteine hydrolase.
AB  - S-Adenosylhomocysteine hydrolase (AdoHcy-nase) is a key enzyme in
      transmethylation reactions. The objective of the present study was to examine the
      potential antiretroviral activities of novel mechanism-based irreversible AdoHcy
      nase inhibitors. (Z)-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (ZDDFA), (E)
      4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (EDDFA), (Z)-4',5'-didehydro-5'-deoxy
      5'-chloroadenosine (ZDDCA) and 5'-deoxy-5'-acetylenic adenosine (DAA) inhibited
      AdoHcy-nase activity with Ki values of 0.55, 1.04, greater than 10.0 and 3.30
      microM, respectively. These four compounds were tested for antiviral activity in
      vitro against Moloney leukemia virus (MoLV) in the XC-plaque assay. MoLV
      replication in murine fibroblasts (SC-1) was inhibited by ZDDFA, EDDFA and DAA
      with IC50 values of 0.05, 0.25 and 3.30 micrograms/ml, respectively. ZDDCA did
      not inhibit MoLV infection at the concentrations tested. Antiviral activity
      correlated with the ability of the individual compounds to maintain sustained
      elevations in intracellular S-adenosylhomocysteine (AdoHcy) concentrations in the
      SC-1 cells. ZDDFA, the most potent inhibitor of AdoHcy-nase and MoLV was also the
      most active in maintaining sustained elevations in intracellular AdoHcy levels.
      The antiviral activity of ZDDFA was also examined in murine C3H1OT1/2 fibroblasts
      which constitutively produce MoLV. Pretreatment with ZDDFA (1.0 microgram/ml) for
      24 hr inhibited virus production by 88%. Similar to the SC-1 cells, and
      concomitant with enzyme inhibition, there was a 300-fold increase in AdoHcy
      levels in ZDDFA (1.0 microgram/ml) treated C3H1OT1/2 cells. Incorporation of a
      [3H]methyl group from tritiated S-adenosylmethionine into total RNA in C3H1OT1/2
      cells was inhibited by ZDDFA without affecting cell viability. These results
      suggest that mechanism-based inhibitors of AdoHcy-nase, such as ZDDFA, may have
      potential as antiretroviral agents.

PMID- 1374146
TI  - Cobalamin (vitamin B12) repression of the Cob operon in Salmonella typhimurium
      requires sequences within the leader and the first translated open reading frame.
AB  - Expression of the Cob operon in Salmonella typhimurium is repressed by cobalamin
      (Cbl). Here it is shown that Cbl repression is mediated by a post-transcriptional
      regulatory mechanism that requires sequences within the leader and the first
      translated open reading frame, the cbiA gene. Transcriptional and translational
      Cob::lacZ fusions containing various lengths of Cob DNA were analysed. In a
      translational Cob::lacZ fusion 407 bp of leader sequence (+69 to +476) was
      sufficient to confer normal repression. However in a transcriptional Cob::lacZ
      fusion a 618 bp region (+69 to +687) was required for normal repression. This 618
      bp region included sequences in the leader as well as sequences within the cbiA
      gene. Point mutations which resulted in loss of repression control were isolated
      and shown to be clustered in the leader sequence (+257 to +380). This region
      contains a putative hairpin-loop structure which we propose functions as an RNA
      operator site for a vitamin B12-responsive repressor protein.

PMID- 1374147
TI  - Differential levels of fertility inhibition among F-like plasmids are related to
      the cellular concentration of finO mRNA.
AB  - The FinOP system of F-like plasmids consists of an antisense RNA (FinP) and a 22
      kDa protein (FinO) which act in concert to prevent the translation of TraJ, the
      positive regulator of the transfer operon. Earlier studies suggested that two
      different variants of finO were responsible for differential levels of fertility
      inhibition among F-like plasmids. We have shown that these variations are due to
      the presence of an additional open reading frame (orf286) upstream of the finO
      gene of conjugative plasmids that are highly repressed for transfer. When orf286
      and finO are linked in cis, the level of FinO expression is increased because of
      a rise in the cellular concentration of finO mRNA. orf286 frameshift and deletion
      mutants also gave the same concentration of finO transcript, suggesting that the
      effect is due to mRNA stabilization. We suggest that the levels of fertility
      inhibition exhibited by F-like plasmids are a function of their cellular FinO
      concentration.

PMID- 1374148
TI  - Processing of a polycistronic mRNA requires a 5' cis element and active
      translation.
AB  - We have characterized a major processed species of mRNA in the his operon of
      Salmonella typhimurium. In vivo and in vitro analyses of the his transcripts from
      wild-type and mutant strains using S1 nuclease protection assays, measurements of
      RNA stability, deletion mapping, gel retardation, and in vitro translation assays
      demonstrate that the distal portion of the polycistronic his mRNA is processed,
      resulting in increased stability. The processing event requires an upstream cis
      acting element and translation of the cistron immediately downstream of the 5'
      end of the processed species. The cistrons contained in this segment are also
      independently transcribed from an internal promoter which is maximally active in
      the absence of readthrough transcription from the primary promoter.

PMID- 1374150
TI  - Past plagues and modern biotechnology.

PMID- 1374149
TI  - Reversal of radiation-induced neutropenia by granulocyte colony-stimulating
      factor.
AB  - Myelosuppression is a common sequelae of radiotherapy, occasionally delaying the
      completion of treatment. In this report, we describe successful reversal of
      radiation-induced neutropenia in a child receiving craniospinal irradiation by
      granulocyte colony-stimulating factor (G-CSF). We suggest that G-CSF be
      considered as supportive care in patients in whom neutropenia develops during
      radiotherapy.

PMID- 1374151
TI  - Faster rates of DNA unwinding under alkaline conditions in xrs-5 cells may
      reflect chromatin structure alterations.
AB  - The Chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive mutant
      isolated from CHO-K1 cells. The radiation sensitivity is associated with a defect
      in DNA double-strand break rejoining. The DNA alkaline unwinding technique was
      used to measure the DNA single-strand breakage caused by gamma-rays in xrs-5 and
      CHO-K1 cells. Greater rates of DNA unwinding were found in xrs-5 cells as
      compared to CHO-K1. Independent measurement of DNA strand breakage by DNA filter
      elution or pulsed-field gel electrophoresis failed to show any difference between
      the two cell lines. The greater rate of unwinding in xrs-5 cells may reflect an
      alteration in chromosome structure.

PMID- 1374152
TI  - Sister-chromatid exchange rates in XX and XY cells of ten chimeric Callithrix
      jacchus individuals.
AB  - In order to ascertain whether or not sister-chromatid exchange (SCE) differs in
      relation to sex, SCE rates in XX and XY cells from 10 specimens of marmoset
      (Callithrix jacchus) were examined. The choice of this primate is particularly
      suitable for three reasons: most individuals have a chimeric constitution, the X
      chromosome is quite large and the Y chromosome is particularly small. Therefore,
      the influence of possible differences in their exposure to the external
      environment can be eliminated. The results obtained did not reveal any
      significant difference between SCE rates in male and female cells in any of the
      examined individuals.

PMID- 1374153
TI  - Electric and/or magnetic field effects on DNA structure and function in cultured
      human cells.
AB  - Exposure of cultured K562 cells to 50 Hz electric (0.2-20 kV/m), magnetic (0.002
      2 G), or combined electric and magnetic fields for up to 24 h did not result in
      the production of detectable DNA lesions, as assayed by the filter elution
      technique. The rate of cell growth was also unaffected as well as the
      intracellular ATP and NAD+ levels. These results indicate that, under the
      experimental conditions utilized in this study, 50 Hz electric, magnetic and
      electromagnetic fields are not geno- and cyto-toxic in cultured mammalian cells.

PMID- 1374154
TI  - Synaptonemal complex alterations in X-irradiated and in oestrogen-treated mice: a
      comparative study.
AB  - Synaptonemal complexes (SCs) were analysed in male NMRI mice either X-irradiated
      or treated with oestradiol benzoate (E2B). Animals 30 days old underwent a single
      X-ray exposure of either 5, 7.5 or 10 Gy and were killed at different times after
      exposure, i.e., 24 h, 1, 4, 12 and 16 weeks. E2B was injected daily to adult mice
      from day 30 to day 60 or up to day 90 of age. Oestradiol was also administered
      during the neonatal period and animals were examined on days 28, 60 and 90 of
      age. Different SC alterations were found in X-irradiated and in E2B-treated mice.
      SC lesions were rare in oestrogen-treated adult mice. Among SC anomalies,
      asynapsis and fragmentation of SC were common lesions. However, the former was
      more frequent in E2B-treated mice, whereas the latter was more frequent in X
      irradiated mice. Quadri- or multi-valents, bridges between bivalents, rings and
      loops were exclusively encountered in the latter, whereas heterotelomeric
      associations seemed to be specific in E2B-treated animals. The mechanisms of the
      different SC lesions are discussed.

PMID- 1374155
TI  - Application of the standard mutagenesis assay results in underestimation of ethyl
      methanesulphonate-induced mutations to ouabain-resistance in Chinese hamster
      cells.
AB  - Chinese hamster V79 cells were exposed to ethyl methanesulphonate (EMS) and the
      incidence of mutant cells resistant to 8-azaguanine (8AZG), 6-thioguanine (6TG)
      or ouabain (OUA) was determined both by the respreading and the in situ
      techniques. In the former assay, the mutagen-treated cultures were grown for
      several days to permit the expression of mutations after which the cells were
      trypsinized, replated (10(5) cells/100-mm dish), and grown in medium supplemented
      with a selective agent. In the in situ assay, cultures were left undisturbed
      between EMS treatment and incubation in the presence of the selective agents. The
      yield of 8AZG-resistant mutants observed at optimal expression times after EMS
      treatment was comparable for both techniques; the induced mutation frequency
      (corrected for spontaneous mutation frequency) was estimated to be 82 x 10(-6)
      mutations per viable cell per unit dose (mM) of EMS. The frequency of 6TG
      resistant mutants equalled 45 and 4 x 10(-6)/mM EMS as determined by the
      respreading and the in situ assays, respectively. In sharp contrast to that
      observed with 6TG, the frequency of OUA-resistant mutants scored by the in situ
      assay (30 x 10(-6)/mM EMS) proved to be an order of magnitude greater than that
      determined by the respreading assay (3 x 10(-6)/mM EMS). Our data therefore
      indicate that, when OUA is used for mutant selection, the application of the
      respreading technique, which has been widely adopted as the standard mammalian
      mutational assay over the past decade, may result in a marked underestimation of
      the actual mutation frequency (approximately 10-fold in V79 cells).

PMID- 1374156
TI  - A recA-ada hybrid gene inducible by DNA damage.
AB  - A damage-inducible expression vector was constructed in which the original recA
      structural gene was replaced by the protein-coding region of the ada gene. The O6
      alkylguanine-DNA alkyltransferase encoded by the ada gene can be measured by a
      rapid and highly sensitive assay. The introduction of this construct into an
      appropriate host cell provides an effective bacterial assay for genotoxins.

PMID- 1374157
TI  - The effect of caffeine on DAPI-inducible fragile sites.
AB  - DAPI is a non-intercalating compound which binds specifically to the AT bases of
      DNA. When leukocytes are grown in complete medium (RPMI 1640) DAPI induces the
      expression of three fragile sites on human chromosomes and if the medium is
      deficient in folic acid and thymidine (199M) it induces 19 fragile sites.
      Caffeine has been found by different authors to considerably enhance the
      expression of chromosome breaks which have been produced by other agents. When it
      is added to the complete medium after DAPI, it elicits almost all the sites that
      DAPI only induces in incomplete medium. When caffeine is added after DAPI to
      incomplete medium, it does not significantly or unidirectionally modify the
      capacity of the two subjects examined to elicit fragile sites. The analysis of
      these results, when correlated with that of the mitotic index, reveals a
      different sensitivity of the two subjects to the combined DAPI-caffeine
      treatment. The results are quite compatible with the hypothesis that the DAPI
      induced fragile sites are DNA regions which are not accurately replicated during
      the S phase.

PMID- 1374158
TI  - Camptothecin-induced sister-chromatid exchange dependent on the presence of
      bromodeoxyuridine and the phase of the cell cycle.
AB  - Camptothecin (CPT), a DNA topoisomerase I inhibitor, dose-dependently induced
      sister-chromatid exchanges (SCEs) in human lymphoblastoid cells NL3 when added
      with bromodeoxyuridine (BrdUrd) for 2 cell cycles. CPT given prior to the
      addition of BrdUrd scarcely induced SCEs. When cells with BrdUrd present for 2
      cell cycles were treated with CPT in the first cell cycle, the SCE induction was
      evident, though its frequency was considerably lower than in cells treated in the
      second cell cycle, indicating that BrdUrd is essential for SCE induction by CPT.
      The replacement of BrdUrd with thymidine in the second cell cycle gave the same
      results in SCE induction and its removal without replacement resulted in a
      reduced but still clear induction by CPT treatment in the second cell cycle.
      These results indicate that BrdUrd, not only incorporated into DNA but also in
      the culture medium, plays an essential role in SCE induction by CPT. CPT
      treatment in the G1 phase of the second cell cycle also induced SCEs, as did
      treatment in the S phase. In phytohemagglutinin-stimulated peripheral
      lymphocytes, CPT given in the G1 phase of the second cell cycle, but not of the
      first one, also induced SCEs though to a lesser degree. These findings suggest
      that CPT is capable of inducing DNA lesions during the G1 phase when chromosomes
      contain BrdUrd-substituted DNA. The lesions are presumably formed in connection
      with transcription, which requires topoisomerase I activity, and are believed to
      be long-lived enough to induce SCEs in the following S phase.

PMID- 1374159
TI  - Influence of cinnamaldehyde on UV-induced gene conversion and point mutation in
      yeast: effect on protein synthesis.
AB  - The activity of cinnamaldehyde (CIN), a bioantimutagen in bacterial systems, was
      tested in the D7 strain of yeast Saccharomyces cerevisiae. Yeast cells were UV
      irradiated and post-incubated in liquid growth medium for 2 and 4 h with
      different concentrations of cinnamaldehyde. During the post-incubation period,
      DNA-damage-specific functions may be induced. This in turn may affect the
      genotoxicity and in fact a weak decrease in UV-induced convertant and revertant
      frequencies was observed after 4 h of post-incubation. The presence of CIN in the
      growth medium increased the UV-induced gene conversion and reversion. The
      addition of cycloheximide abolished this effect. To evaluate the CIN effect on
      protein synthesis, extracts of cells UV-treated and post-incubated for 2 h in the
      presence of 35S-methionine were performed. SDS-gel electrophoresis demonstrated
      the inhibitory effect of CIN on a UV-specific protein. This work suggests that
      CIN might interfere with DNA-damage-inducible systems although it did not exert
      an antimutagenic activity in our experimental conditions.

PMID- 1374160
TI  - Developmental regulation of protein synthesis in schistosomes.
AB  - Soon after infecting a mammalian host, cercariae of Schistosoma mansoni rapidly
      undergo a series of morphologic and biochemical adaptations associated with
      transformation to their next developmental stage, the schistosomulum. Few of
      these changes are associated with alterations in gene expression except for an
      apparent increase in protein synthesis. By pulse-labeling, we demonstrate that
      there is a gradual rise in methionine incorporation after transformation, and
      that the rise is not due to increasing amino acid uptake or increasing protein
      stability. This pattern of protein synthesis did not result from a general
      increase in transcription of mRNA. There was likewise no evidence of a rise in
      the availability of selected rate limiting components of the translational
      machinery such as rRNA or elongation factor 1 alpha as a mechanism for increasing
      levels of translation. Transcription of HSP 70 appears to be induced in both
      cercariae and schistosomula, though translation of this message was not detected.
      A comparison between the level of in vivo synthesis of proteins and the level of
      their corresponding mRNAs suggests that following transformation of cercariae to
      schistosomula the translation of most mRNAs is blocked and that this block is
      gradually reversed during the first 24 h.

PMID- 1374161
TI  - Interferons--expanding therapeutic roles.

PMID- 1374162
TI  - RNA editing. Guides to experiments.

PMID- 1374163
TI  - In vitro guide RNA/mRNA chimaera formation in Trypanosoma brucei RNA editing.
AB  - The post-transcriptional processing of various mitochondrial transcripts in
      kinetoplastids, kRNA editing, adds and removes uridines, producing mature
      messenger RNAs. This editing seems to be directed by 'guide' RNAs (gRNAs) which
      are complementary to portions of the mature message. The editing mechanism has
      been proposed to entail transesterification. Detection of chimaeric gRNA-mRNA
      molecules, intermediates predicted by transesterification, support this model. We
      report here the in vitro formation of such chimaeras where endogenous gRNAs are
      covalently linked to added synthetic mRNA. Addition of gel-purified gRNAs to the
      standard reaction mix increases chimaera formation. This increase is not observed
      when the gRNA 3'-hydroxyl group is chemically modified, identifying this terminal
      hydroxyl as the reactive group. These results provide the first experimental
      evidence for an in vitro RNA editing event and support the involvement of
      transesterification as a chemical mechanism.

PMID- 1374164
TI  - Functional characterization of a heteromeric NMDA receptor channel expressed from
      cloned cDNAs.
AB  - The glutamate receptor (GluR) channel plays a key part in brain function. Among
      GluR channel subtypes, the NMDA (N-methyl-D-aspartate) receptor channel which is
      highly permeable to Ca2+ is essential for the synaptic plasticity underlying
      memory, learning and development. Furthermore, abnormal activation of the NMDA
      receptor channel may trigger the neuronal cell death observed in various brain
      disorders. A complementary DNA encoding a subunit of the rodent NMDA receptor
      channel (NMDAR1 or zeta 1) has been cloned and its functional properties
      investigated. Here we report the identification and primary structure of a novel
      mouse NMDA receptor channel subunit, designated as epsilon 1, after cloning and
      sequencing the cDNA. The epsilon 1 subunit shows 11-18% amino-acid sequence
      identity with rodent GluR channel subunits that have been characterized so far
      and has structural features common to neurotransmitter-gated ion channels.
      Expression from cloned cDNAs of the epsilon 1 subunit together with the zeta 1
      subunit in Xenopus oocytes yields functional GluR channels with high activity and
      characteristics of the NMDA receptor channel. Furthermore, the heteromeric NMDA
      receptor channel can be activated by glycine alone.

PMID- 1374165
TI  - Molecular and biological characterization of a murine ligand for CD40.
AB  - The CD40 surface molecule is a 277-amino-acid glycoprotein expressed on B
      lymphocytes, epithelial cells and some carcinoma cell lines. Monoclonal
      antibodies against CD40 mediate a variety of effects on B lymphocytes, including
      induction of intercellular adhesion, short- and long-term proliferation,
      differentiation and enhanced tyrosine phosphorylation of proteins. In addition,
      germinal centre centrocytes are prevented from undergoing apoptosis by activation
      through CD40 and receptor for antigen. These data indicate that CD40 could be a
      receptor for an unknown ligand with important functions in B-cell development and
      activation. This hypothesis is strengthened by the homology of the extracellular
      region of the CD40 molecule with a family of cell-surface glycoproteins that
      includes the receptors for nerve growth factor and tumour necrosis factor. Here
      we report the cloning of a ligand for CD40 that is expressed on the cell surface
      of activated T cells and mediates B-cell proliferation in the absence of co
      stimulus, as well as IgE production in the presence of interleukin-4.

PMID- 1374166
TI  - Structure of HIV-1 reverse transcriptase/DNA complex at 7 A resolution showing
      active site locations.
AB  - AIDS, caused by human immunodeficiency virus (HIV), is one of the world's most
      serious health problems, with current protocols being inadequate for either
      prevention or successful long-term treatment. In retroviruses such as HIV, the
      enzyme reverse transcriptase copies the single-stranded RNA genome into double
      stranded DNA that is then integrated into the chromosomes of infected cells.
      Reverse transcriptase is the target of the most widely used treatments for AIDS,
      3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI), but resistant
      strains of HIV-1 arise in patients after a relatively short time. There are
      several nonnucleoside inhibitors of HIV-1 reverse transcriptase, but resistance
      to such agents also develops rapidly. We report here the structure at 7 A
      resolution of a ternary complex of the HIV-1 reverse transcriptase heterodimer, a
      monoclonal antibody Fab fragment, and a duplex DNA template-primer. The double
      stranded DNA binds in a groove on the surface of the enzyme. The electron density
      near one end of the DNA matches well with the known structure of the HIV-1
      reverse transcriptase RNase H domain. At the opposite end of the DNA, a
      mercurated derivative of UTP has been localized by difference Fourier methods,
      allowing tentative identification of the polymerase nucleoside triphosphate
      binding site. We also determined the structure of the reverse transcriptase/Fab
      complex in the absence of template-primer to compare the bound and free forms of
      the enzyme. The presence of DNA correlates with movement of protein electron
      density in the vicinity of the putative template-primer binding groove. These
      results have important implications for developing improved inhibitors of reverse
      transcriptase for the treatment of AIDS.

PMID- 1374167
TI  - Psychomotor development in children of mothers with epilepsy.
AB  - The risk of psychomotor retardation and the prevalence of mental subnormality are
      slightly increased in offspring of mothers with epilepsy. The prevalence rates of
      mental deficiency observed in population-based studies have been lower than those
      in reports of hospital-based studies. In addition to use of antiepileptic drugs
      (AEDs), several other factors associated with maternal epilepsy, such as seizures
      during pregnancy, inherited brain disorders, and nonoptimal psychosocial
      environment, can affect the child's psychomotor development. None of the major
      AEDs carries any special risk for mental retardation. However, polytherapy and
      inherited deviations in AED metabolism in the fetus probably do increase the risk
      for mental retardation.

PMID- 1374168
TI  - [Intestinal lymphoma. A report of 2 cases].

PMID- 1374169
TI  - Eosinophilic globules resembling Mallory bodies in a renal cell carcinoma.

PMID- 1374170
TI  - Synovial chondromatosis with cranial extension.
AB  - Synovial chondromatosis is a benign arthropathy characterized by metaplasia in
      synovial membranes that can produce detached particles of cartilage. It occurs
      most often in the knee, hip, and elbow but has been reported in the
      temporomandibular joint. This is a rare presentation of synovial chondromatosis
      with glenoid fossa erosion and cranial extension.

PMID- 1374171
TI  - Immunohistochemical evaluation of oral myxoid lesions.
AB  - Oral examples of neurothekeomas (nerve sheath myxomas), soft tissue myxomas, and
      focal mucinous and odontogenic myxomas were examined for selected markers. With
      the use of avidin-biotin complex staining procedures, these specimens of lesions
      were stained with antibodies to S-100 protein, neurospecific enolase,
      neurofilaments, desmin, and vimentin. Our results show that the use of
      immunohistochemical markers for these neural antigens can aid in distinguishing
      nerve sheath myxomas from other oral myxoid lesions.

PMID- 1374172
TI  - Behavioral assessment of children and adolescents.
AB  - Primary care visits provide opportunities for behavioral assessment of children
      and adolescents. Screening checklists, interviewing, behavioral observations, and
      parent and child monitoring of behavior are feasible assessment techniques for
      ongoing assessment of the child's behavioral and developmental status. The
      incorporation of behavioral assessment in primary care will result in better
      identification of children's behavioral and developmental problems and an
      improved health care system that is responsive to all aspects of children's
      health.

PMID- 1374173
TI  - Collaborative planning between pediatricians and special educators.
AB  - The pediatrician is often the first professional consulted when parents are
      concerned that their child might have a developmental disability. Current federal
      laws providing education and related services for the disabled have included the
      pediatrician as a participant in accessing services available to this population
      from birth through age 21. A review of the elements of these laws and how the
      pediatrician can take a more active role with the disabled population is
      presented, and case examples are cited.

PMID- 1374174
TI  - Update on the Denver II.
AB  - Despite widespread usage of the original Denver Developmental Screening Test,
      there have been criticisms of the tool. The updated Denver II tool addresses
      several concerns associated with the original test.

PMID- 1374175
TI  - Prostate specific antigen in diagnosis, staging, and follow-up of prostate
      cancer.

PMID- 1374176
TI  - Rectal examination and ultrasonography in the diagnosis of prostate cancer.
AB  - Most patients with prostate cancer have disease that has extended beyond the
      confines of the gland at the time of diagnosis. The effect of earlier detection
      on morbidity and death requires further study, as does assessment of prognostic
      factors and optimal therapy for individual patients. Recent reports indicate the
      utility of using prostate specific antigen and digital rectal examination as
      preliminary tests to identify patients in whom further study by prostate
      ultrasonography will improve detection rates. The algorithm presented may be a
      useful guide in sequencing detection approaches. The value of mass screening for
      prostate cancer by any existing means remains unproven.

PMID- 1374177
TI  - Magnetic resonance spectroscopy in prostate disease: diagnostic possibilities and
      future developments.
AB  - Magnetic resonance spectroscopy (MRS) is a relatively new technique for studying
      membrane and intracellular metabolic events occurring in cancer. A series of
      transrectal probes were used for performing MRS and subsequently for integrated
      MRS/magnetic resonance imaging (MRI) of the prostate. Studies using transrectal
      31P/1H MRS showed that it can characterize metabolic differences between normal
      and malignant prostates. Specifically, malignant prostates are characterized by
      low levels of phosphocreatine and citrate and high levels of phosphomonoesters
      relative to normal glands. These findings were verified in biochemical studies of
      prostate biopsies. The images obtained by transrectal coil techniques were
      superior to images obtained by the conventional body coil technique. In the
      future, the integration of 1H imaging and multi-volume localization techniques
      (spectroscopic imaging) will allow the acquisition of metabolic maps of the
      prostate which may eventually be useful in diagnosis and in management of
      patients with prostate cancer.

PMID- 1374178
TI  - Volume of normal prostate, of prostate cancer, and of benign prostatic
      hyperplasia: are correlations with prostate specific antigen clinically useful?
AB  - This retrospective study correlated prostate volume, determined by transrectal
      ultrasonography, with serum prostate specific antigen (PSA), by Deming regression
      analysis, in patients with confirmed benign prostatic hyperplasia (BPH) and
      patients with non-metastatic (M0) or metastatic (M1) prostate cancer. In BPH, a
      highly significant correlation was found between log10[PSA] and prostate volume.
      When this PSA/volume regression pattern for BPH was used as a reference standard,
      all 17 patients with M1 prostate cancer and 83% of the 23 patients with M0
      disease were discriminated from BPH.

PMID- 1374179
TI  - Prostatic intraepithelial neoplasia (PIN): morphological clinical significance.
AB  - Premalignant lesions of the prostate fall into two categories. The first category
      includes formation of new, usually small, glands which are either abnormally
      distributed or show minimal nuclear atypia or both. Morphologically, this lesion
      presents the differential diagnostic alternatives of micro-acinar hyperplasia on
      the one hand and a low grade micro-acinar cancer on the other. If the presence or
      absence of nuclear anaplasia or acinar dispersion (i.e., stromal invasion) raises
      any degree of doubt, atypical glands are diagnosed. This is the category that is
      considered by some to be the precursor of well differentiated prostate cancer.
      The second category is prostatic intraepithelial neoplasia (PIN). We have defined
      PIN as an intra-acinar or ductal proliferation of secretory cells with
      unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3
      invasive prostate cancer. We consider PIN as essentially carcinoma in situ. The
      lesion designated by some as PIN 1 is classified by us as atypical hyperplasia.

PMID- 1374180
TI  - Osteocalcin: is it a useful marker of bone metastasis and response to treatment
      in advanced prostate cancer?
AB  - Serum osteocalcin (OC) is derived largely from new cellular synthesis. It is a
      marker for bone formation and a noninvasive specific marker of osteoblastic
      activity. The clinical significance of OC in monitoring prostatic cancer bone
      metastases was evaluated. Pretreatment serum OC levels were determined with a
      radioimmunoassay kit in a total of 63 patients with prostate cancer (8 with stage
      B, 12 with stage C, 12 with stage D1, and 31 with metastatic bone disease). The
      OC levels in patients with skeletal metastasis were significantly higher than
      those in patients without bony lesions (P less than 0.01). The pattern of the
      initial changes in OC levels were analyzed in patients with skeletal metastasis
      who received endocrine treatment. The pretreatment OC value is of little use in
      predicting the response to treatment. The patients whose OC level initially
      increased and remained high tended to have a shorter interval to disease
      progression. On the other hand, the pattern of initial changes in OC varied
      according to the regimen of endocrine treatment. Our study suggests that OC seem
      to reflect the response to treatment and might lead to the improvement in follow
      up procedures. However, the clinical significance of OC as a marker of the
      response of bone metastasis should be carefully discussed with regard to the
      direct hormonal effect on bone metabolism.

PMID- 1374181
TI  - Effect of pentosan, a novel cancer chemotherapeutic agent, on prostate cancer
      cell growth and motility.
AB  - Pentosan is a new chemotherapeutic drug which is currently in Phase I clinical
      trials. In our experimental systems, in vivo, pentosan inhibits the growth of the
      highly metastatic MAT-LyLu (MLL) Dunning R3327 prostate cancer cell line only at
      toxic doses and has no apparent effect on growth in vitro. The mechanism of tumor
      inhibition of this drug is unknown; however, in vitro, pentosan exhibits a potent
      inhibition of cell motility. Cell motility is essential for tumor cell metastasis
      and angiogenesis. By blocking cell motility, pentosan has the potential to
      inhibit both tumor growth and metastasis. We have characterized the mechanism of
      motility inhibition by pentosan and believe it alters cell-extracellular matrix
      interactions. The mechanism of motility inhibition by pentosan appears to be
      independent of cytoskeletal structural alterations, including changes in
      microfilament and microtubule networks. Pentosan acts through a different
      mechanism than suramin, a drug which inhibits motility through inhibition of
      growth factor effects. In vitro, pentosan alters cellular contacts with the
      extravascular matrix and inhibits cell motility. In vivo, pentosan prolongs
      survival of rats injected with MLL cells by 25%, but did not appear to decrease
      the rate of primary tumor growth or the number of metastatic lesions in the
      treated animals. These data suggest that, in vivo, pentosan acts through an as
      yet undefined mechanism.

PMID- 1374183
TI  - Shwachman syndrome: a case report.
AB  - Cutaneous involvement is frequent in Shwachman syndrome, and includes various
      degrees of dry skin, and eczematous and ichthyosiform lesions. A 12-year-old boy
      with Shwachman syndrome had cutaneous involvement characterized by dry skin,
      perioral dermatitis, and follicular keratosis. Polymorphonuclear motility was
      decreased. A nutrition work-up showed a decrease in liposoluble vitamins, and
      suggested a causative link with the skin lesions.

PMID- 1374182
TI  - Relationship of proliferating cell nuclear antigen (PCNA) in prostatic carcinomas
      to various clinical parameters.
AB  - Proliferating cell nuclear antigen (PCNA) expression was determined
      immunohistochemically, using a monoclonal antibody PC10, in 102 prostatic
      carcinoma samples and in prostate tissue from 21 patients with benign prostatic
      hyperplasis (BPH). The percentage of cells with stained nuclei ranged from 1% to
      58% in the carcinoma specimens and 0% to 10% in the BPH specimens. A
      semiquantitative scoring system was devised for the degree of PCNA positivity
      observed in the tumors. Statistical analysis of the PCNA score in relation to the
      histological grade of the tumors gave a significant positive or negative
      correlation between these parameters P less than 0.001. No significant
      correlation between PCNA score was, however, seen with metastatic status, T
      category (TMN classification) of the primary tumor, or the patient's age at
      diagnosis. In 65 prostatic cancer patients of known survival, those individuals
      whose tumors had a PCNA score of +/- (less than 10% of nuclei stained) were
      compared with those patients whose tumors were either 1+, 2+, or 3+ (greater than
      10% of nuclei stained). Life table analysis of the two groups indicated that the
      patients with the lower PCNA score survived significantly longer than those with
      the higher PCNA scores, P less than 0.04. Comparison of the Ki-67 expression in
      frozen sections with the PCNA expression in wax-embedded tissue of 86 prostatic
      carcinomas was also undertaken. A significant correlation between these two
      parameters was found, P less than 0.001, although the growth fraction estimated
      by Ki-67 expression was generally lower than that given by the PCNA scoring
      system.

PMID- 1374184
TI  - Digestibility of proteins and starch (in vitro) of amphidiploids (black gram x
      mung bean) as affected by domestic processing and cooking.
AB  - The effects of different domestic processing and cooking methods on starch
      digestibility (in vitro) and protein digestibility (in vitro) of four strains of
      amphidiploids (black gram x mung bean) were investigated. An increase of 35 to
      48% and 22 to 25% was observed in starch digestibility and protein digestibility,
      respectively, when the seed of amphidiploids were soaked for 18 h. Cooking (both
      of unsoaked and soaked seeds) and germination improved significantly the starch
      digestibility and protein digestibility of all the varieties.

PMID- 1374185
TI  - Commercial soybean starch blocker consumption: impact on weight gain and on
      copper, lead and zinc status of rats.
AB  - A commercial 'starch blocker' was used to study the digestion of starch (potato)
      in mature female rates for four weeks. Two levels of 'starch blocker' were used.
      The first level was calculated to inhibit starch digestion at 50%, the second was
      calculated to inhibit starch digestion at 100%. No significant effects on the
      body weights (271.10 +/- 29, 277.7 +/- 43, 259.1 +/- 25 g) were found among the
      groups of rats at 0%, 50% and 100% inhibition levels, respectively. Feed intakes
      were not affected. However, fecal copper and zinc excretions increased
      significantly (p less than 0.05) due to the inhibitors. Fecal copper excretions
      were 0.468 +/- 0.14, 0.578 +/- 0.09, 0.617 +/- 0.07 mg/rat/week, while fecal zinc
      values were 0.625 +/- 0.14, 0.859 +/- 0.32 and 0.778 +/- 0.26 mg/rat/week when no
      inhibitor was fed, at 50% inhibition and at 100% inhibition respectively. Thus,
      while use of 'starch blockers' did not promote weight loss in the mature female
      rats, utilization of copper and zinc were negatively affected.

PMID- 1374186
TI  - Correlation of morphologic diagnosis of Pneumocystis carinii with the presence of
      pneumocystis DNA amplified by the polymerase chain reaction.
AB  - We compared the presence of P. carinii in clinical specimens as detected by
      standard cytomorphologic techniques with amplification of P. carinii-specific DNA
      by the polymerase chain reaction (PCR). Results correlated in 33 of 37 instances
      (89%): nine specimens were positive by both PCR and morphology; 24 specimens were
      negative by both techniques. Two specimens from one patient were obtained 3 days
      apart. The first specimen was both cytologically and PCR negative, while the
      second specimen was both cytologically and PCR positive for P. carinii. At least
      in some instances, therefore, PCR is no more sensitive than morphology, and other
      factors such as specimen adequacy are more important. Twelve of the 24 negative
      specimens were from patients with prior histories of P. carinii pneumonia,
      suggesting that recurrent disease may be from reacquisition of organisms in
      previously exposed individuals, rather than reactivation of latent organisms.
      Discrepant results included three morphologically negative specimens that were
      positive by PCR. It remains to be determined whether the increased sensitivity of
      PCR in these cases is real or artifactual. One morphologically positive specimen
      was negative by PCR. Polymerase chain reaction correlates well with
      cytomorphologic diagnosis of P. carinii pneumonia and may be a valuable
      diagnostic and epidemiologic tool.

PMID- 1374187
TI  - Immunocytochemical staining of fine-needle aspiration biopsies of the liver as a
      diagnostic tool for hepatocellular carcinoma.
AB  - Fine-needle aspiration biopsy (FNAB) under ultrasonographic or computerized
      tomographic guidance is a useful diagnostic procedure for hepatic neoplasms.
      However, cytologic criteria alone may not allow for the distinction of
      hepatocellular carcinomas (HCC) from cholangiocarcinomas (CC) and metastatic
      adenocarcinomas (MA). In an effort to refine the FNAB diagnosis of hepatic
      malignancies, a panel of immunocytochemical stains was applied to aspiration
      specimens from primary and metastatic carcinomas in the liver. Anticytokeratin
      antibodies with different specificities (Cam 5.2 and AE1) were used in
      conjunction with antibodies to carcinoembryonic antigen (CEA), alpha-fetoprotein
      (AFP), and alpha-1-antitrypsin (AAT). All HCC, CC, and MA were immunoreactive
      with the antikeratin antibody Cam 5.2. However, only three (15%) HCC were
      positive with AE1, in contrast to 100% of CC and MA. Antibodies to CEA and AFP
      were also helpful diagnostic aids, especially for the three HCC that were
      immunoreactive with AE1. Canalicular staining for CEA was present in 47% of HCC,
      but in none of the CC or MA. AFP positivity occurred in 45% of HCC, but only one
      CC and none of the MA. AAT was not a useful marker for HCC due to low sensitivity
      and specificity. Immunocytochemistry is an effective adjunct to the cytodiagnosis
      of malignant liver tumors sampled by FNAB.

PMID- 1374188
TI  - Altered distribution of desmin filaments in hypertrophic cardiomyopathy: an
      immunohistochemical study.
AB  - Hypertrophic cardiomyopathy (HCM) is characterized by myofiber hypertrophy and
      disarray. Intermediate filaments play an important role in maintaining of normal
      cell shape. Desmin filaments have been detected in adult cardiomyocytes, and
      vimentin and keratin filaments in cardiomyocytes during embryonic development.
      The pattern of arrangement of intermediate filaments in HCM has not been
      reported. We examined the distribution of intermediate filaments in formalin
      fixed tissue sections of the disarrayed myofibers from 10 hearts with HCM using
      an immunohistochemical technique and antibodies to desmin, vimentin, and high and
      low molecular weight keratins. The controls consisted of subaortic tissue from
      surgically explanted hearts of patients with ischemic heart disease. In the
      ischemic hearts, desmin was detected in the Z bands and intercalated disks. In
      all HCM cases, three patterns of staining for desmin were noted: (a) individual
      myocytes showing a parallel arrangement along Z bands; (b) focal myofibers with
      decreased or complete loss of labeling of Z bands; and (c) individual myocytes
      with intense granular cytoplasmic staining especially in disarrayed myofibers. No
      staining for vimentin or keratins was noted in the cardiomyocytes from either the
      HCM or ischemic cases. The altered arrangement of desmin filaments in the
      disarrayed cardiac muscle fibers may play a role in the altered contractility
      that occurs in patients with HCM.

PMID- 1374189
TI  - Immunostaining for P-glycoprotein in the diagnosis of thyroid carcinomas.
AB  - The morphologic distinction between thyroid carcinoma and certain benign thyroid
      conditions can be difficult in selected cases. P-glycoprotein (Pgp), a
      glycoprotein associated with tumor multidrug resistance, has been reported to be
      expressed in thyroid carcinoma but not in benign thyroid conditions. To determine
      the specificity of immunostaining for Pgp in the diagnosis of thyroid carcinoma,
      we studied formalin-fixed, paraffin-embedded tissue from 69 cases of various
      thyroid lesions using a commercially available monoclonal antibody to Pgp (C219,
      Centocor, Malvern, PA) and an avidin-biotin-peroxidase complex technique.
      Positive reactivity was seen in 15 of 37 (41%) benign thyroid conditions and in
      23 of 32 (72%) thyroid carcinomas. We conclude that immunostaining for Pgp is not
      specific in the diagnosis of thyroid carcinoma.

PMID- 1374190
TI  - The influence of dose and time on the cure of larynx tumors.

PMID- 1374191
TI  - Influence of opioids on substance P release evoked by antidromic stimulation of
      primary afferent fibers in the hind instep of rats.
AB  - The effect of opioids on the release of immunoreactive substance P (iSP)
      following simultaneous electrical stimulation of the sectioned sciatic and
      saphenous nerves was examined by perfusion of the subcutaneous space in the rat
      instep. Antidromic stimulation of both the nerves caused an increase in iSP
      release, which was dependent on the intensity of stimulation, and an approx. 200%
      increase in Evans blue extravasation. Stimulation-induced iSP release and
      extravasation were suppressed by pretreatment with capsaicin (50 mg/kg s.c.) and
      spantide (10 mumol/kg i.p.), respectively. Intra-arterial infusion of morphine
      (30 mumol/kg) or ethylketocyclazocine (30 mumol/kg) or [D-Ala2,D-Leu5]enkephalin
      (30 mumol/kg) inhibited the increase in iSP release evoked by antidromic
      stimulation at 10 V. This inhibitory effect of morphine was antagonized by
      pretreatment with naloxone (2 mg/kg, i.p.). These results suggest existence of
      multiple types of opioid receptor on the peripheral endings of primary afferent
      fibers, that regulate SP release from the peripheral nerve endings into the
      extravascular space.

PMID- 1374192
TI  - Renal, cardiovascular and endocrine effects of centrally administered galanin in
      the anaesthetised rat.
AB  - Several studies implicate galanin as a central neuromodulator with an ability to
      influence hypothalamic and pituitary secretion. Central galanin content is also
      sensitive to the state of body hydration. Cardiovascular, renal and peripheral
      endocrine changes evoked by intracerebroventricular administration of galanin
      have been examined in the anaesthetized rat. Central galanin infusion
      consistently induced a transitory diuresis, the increase in urine flow being
      associated with a reduction in urine osmolality. There was no demonstrable change
      in plasma vasopressin concentration at the end of a 40 min galanin infusion.
      However, plasma aldosterone and corticosterone concentrations were significantly
      reduced by comparison with time-matched vehicle infused controls. There were no
      clear changes in renal electrolyte excretion or in heart rate or mean arterial
      blood pressure during the study period. The findings of this study support a
      participatory role for galanin in body fluid homeostasis, though the mechanisms
      responsible for mediating its central action on urine production remain unclear.

PMID- 1374193
TI  - Vasoactive intestinal polypeptide induces neurogenic contraction of guinea-pig
      ileum. Involvement of acetylcholine and substance P.
AB  - The effect and mode of action of vasoactive intestinal polypeptide (VIP), a
      peptidergic neuromodulator in the gastrointestinal nervous system, were
      investigated in isolated muscle strips of the guinea-pig ileum. VIP induced
      concentration-dependent (20 nM-1 microM) contractions of longitudinal ileal
      strips. TTX (1 microM), a mixture of atropine (3 microM) and spantide (30
      microM), a mixture of atropine (3 microM) and omega-conotoxin GVIA (100 nM),
      somatostatin (60 nM) and dynorphin (100 nM) abolished the effect of VIP. In most
      cases a small relaxation became evident. Desensitization to substance P in the
      presence of atropine prevented VIP-induced contraction. A partial inhibition was
      observed in the presence of atropine (3 microM), spantide (30 microM), omega
      conotoxin GVIA (100 nM), beta-endorphin (265 nM), met-enkephalin (1100 nM) and a
      mixture of spantide (30 microM) and omega-conotoxin GVIA (100 nM). The action of
      VIP was not significantly modified by guanethidine (3 microM) or hexamethonium
      (150 microM). In circular ileal strips VIP (10-300 nM) caused concentration
      dependent relaxations through a direct myogenic effect. These results indicate
      that the VIP produced contractions of the guinea-pig ileum are exclusively
      neurally mediated and involve a cholinergic as well as a noncholinergic
      nonadrenergic (NANC) pathway. It is concluded that besides acetylcholine (Ach)
      VIP releases the peptidergic transmitter substance P from postganglionic nerve
      fibers of myenteric plexus. Opioid peptides and somatostatin modulate the
      activity of cholinergic and peptidegic nerves in the guinea-pig ileum. The
      release of substance P appears to depend completely on N-type voltage sensitive
      calcium channels.

PMID- 1374194
TI  - Properties determining the potential of naturally occurring and vaccine-induced
      human antibodies to protect against lethal infection of Pseudomonas aeruginosa.
AB  - In order to characterize antibodies responsible for the protection against fatal
      infection with Pseudomonas aeruginosa we analysed the fine specificity, avidity
      and protective capacities of naturally occurring anti-lipopolysaccharide (LPS)
      antibodies in two standard human Ig preparations and of vaccine-induced anti-LPS
      antibodies in a hyperimmune Ig preparation. Applying competitive binding assays,
      immunoblotting and an in vivo protection assay, we provide evidence that only
      preparations from immunized volunteers contain significant amounts of antibodies
      which confer detectable protection in a murine burn-wound model. Supported by the
      parallel analysis of monoclonal antibodies, our data suggest that protection by
      passive immunization with anti-LPS antibodies is mediated by antibodies specific
      for the LPS O-chain moiety of the corresponding virulent bacterium. Furthermore,
      our results indicate that protectiveness is restricted to a small population of
      antibodies with high affinity for particular O-chain epitopes.

PMID- 1374195
TI  - Plasminogen activator inhibitor type 1: biochemistry and evidence for modulation
      of fibrinolysis in vivo.

PMID- 1374196
TI  - Palestinian martyr widowhood--emotional needs in conflict with role expectations?
AB  - The phenomenon of martyrdom is described in the context of the Palestinian
      struggle, with emphasis on its implications at the psychosocial level. The
      situation of the martyr widows is discussed, with highlight on their difficult
      double role as mourning individuals under the pressure of social, religious, and
      political expectations.

PMID- 1374197
TI  - Gene expression in ataxia telangiectasia cells as perturbed by bleomycin
      treatment.
AB  - The autosomal recessive genetic disorder ataxia telangiectasia (AT) has been
      characterized in the RNA transcripts of cultured cells. Molecular species of poly
      (A)+ RNA that are present in AT fibroblasts (ATFs) at levels different from those
      in normal human fibroblasts (NHFs) were cloned in the form of cDNAs. Treatment
      with bleomycin, which transiently inhibits DNA synthesis in NHFs but not in ATFs,
      differentiated ATFs and NHFs in the above cloning. Two cDNA clones with an
      identical DNA sequence were isolated, the corresponding RNA transcript of which
      was induced approximately twofold after bleomycin treatment in NHFs, but not in
      ATFs. The DNA sequence of these two cDNA clones, except for its polyadenylation
      part, was identical to the heavy-strand replication origin sequence of human
      mitochondrial DNA. The results indicate the possibility that the induction of
      this RNA transcript is involved in bleomycin-induced inhibition of DNA synthesis
      in normal human cells, while it is defective in AT cells. In addition, the
      previous observation that much fibronectin is produced in AT cells was confirmed
      in this study in terms of RNA transcription.

PMID- 1374198
TI  - Pharmacology and electrophysiology of ATP-activated ion channels.

PMID- 1374199
TI  - Chemotherapy for carcinomas of the penis and urethra.
AB  - The experience with cytotoxic drugs in penile and urethral carcinomas is limited
      to small series, frequently with inconclusive results. However, the preliminary
      evidence indicates that these tumors are responsive to drugs, particularly
      cisplatin, bleomycin, methotrexate, and 5-fluorouracil, as well as combinations
      of these agents. Efforts should continue to identify active regimens, and newer
      therapies such as biologic response modifiers, differentiation-inducing agents,
      and biochemical modulations should be tested vigorously. The potential of
      postoperative or postradiation adjuvant chemotherapy also warrants exploration.
      Because these tumors are so uncommon, penile and urethral carcinomas should be
      the focus of investigations by multi-institutional cooperative groups.

PMID- 1374200
TI  - Changing cytokeratin expression patterns in diethylstilbestrol dipropionate
      induced metaplastic lesions of the goat prostate.
AB  - Five-month-old male goats were treated with 25 mg diethylstilbestrol dipropionate
      (DES-DP) by a single intramuscular injection, causing characteristic histological
      alterations in the peripheral glandular epithelium of the prostate, resulting in
      squamous metaplasia. Using a panel of monoclonal and polyclonal cytokeratin
      antibodies on frozen tissue sections of control prostates, we were able to
      immunohistochemically distinguish between the normal secretory cells, which are
      positive for cytokeratin 18 as detected with the antibody RGE 53, and the
      scattered basal cells, which could be specifically stained by the antibody RCK
      103. Cytokeratins indicating squamous differentiation, i.e., nos 4 and 13,
      recognised by the antibodies 6B10 and 1C7, respectively, were found in sporadic
      cells throughout the normal goat prostate. Profound changes in cytokeratin
      expression were observed in the metaplastic lesions as compared to control
      peripheral glandular tissue. In this respect three monoclonal antibodies are of
      special interest. RCK 103 is immunoreactive with resting and all stages of
      differentiating basal cells. Antibodies 1C7 and 6B10 strongly stain the squamous
      cells in the metaplastic lesions, with 1C7 staining all the squamous cells in the
      lesions except the basal cell layer, and 6B10 being immunoreactive with the same
      suprabasal cells or the more differentiated cells in the upper strata. As a
      result the number of cytokeratin 18-positive cells is drastically reduced upon
      metaplasia. The results indicate that the goat system can be used as a suitable
      model system to further test the applicability of immunohistochemical methods in
      meat inspection and toxicological pathology.

PMID- 1374201
TI  - Prophylactic diclofenac infusions in major orthopedic surgery: effects on
      analgesia and acute phase proteins.
AB  - The influence of diclofenac, given by continuous i.v. infusion starting
      preoperatively, on postoperative pain and inflammation was assessed in a double
      blind, randomized, placebo-controlled study in 40 patients scheduled for major
      orthopedic surgery. Starting 30 min before induction the patients received either
      diclofenac (0.35 mg.kg-1 bolus followed by a constant-rate infusion of 90
      micrograms.min-1) or placebo for 24 h. The pain intensity (VAS) and the amount of
      rescue narcotic (piritramide on demand) were significantly lower in the
      diclofenac group from 4 and 6 h postsurgery, respectively, till end of infusion.
      Acute phase proteins used as inflammation markers (C-reactive protein, alpha 1
      chymotrypsin, alpha 1-acid glycoprotein, haptoglobin and coeruloplasmin) showed
      similar variations in both groups for 24 h. The diclofenac treatment had no
      influence on hematological and coagulation profiles, nor on muscle and liver
      enzymes in comparison with placebo. Both patients and observer rated the
      diclofenac treatment as significantly superior to the placebo treatment.

PMID- 1374202
TI  - Dolichos biflorus agglutinin binding to intracranial germ-cell tumors: detection
      of embryonal components in germinomas.
AB  - Dolichos biflorus agglutinin (DBA) binding was examined in 32 cases of
      intracranial human germ-cell tumors. In embryonal carcinomas, intense DBA binding
      sites were found on the free surface and cytoplasm of embryonal cells. In
      teratomas, glandular structures often had positive DBA binding sites. Yolk sac
      carcinomas and choriocarcinomas showed negative DBA affinity. Of 19 cases of
      germinomas, 10 showed no DBA-positive cells, while sporadically and/or
      collectively distributed-DBA positive cells were found in the other 9 cases.
      Common brain tumors such as gliomas, neurinomas and meningiomas were negative for
      DBA staining. Considering the cellular carbohydrate structure, these findings
      suggest that DBA-positive cells in germinoma might be evidence of differentiation
      into embryonal or some somatic components. In addition, because of the absence of
      DBA binding sites in the common brain tumors, the identification of such binding
      sites in brain tumors might act as a marker for embryonal or somatic components,
      especially among germ-cell tumors.

PMID- 1374204
TI  - An immediate light microscopic response of neuronal somata, dendrites and axons
      to non-contusing concussive head injury in the rat.
AB  - Sixteen rats were killed by transcardial perfusion fixation 1 min after a non
      contusing concussive head injury, and seven rats 1 day later. In each of the "1
      min" animals Golgi-like neurons and long axonal segments scattered in various
      proportions among unstained neurons and axons were demonstrated by a new silver
      method both near to and far from the impact site in a parenchymal environment
      unaffected by contusion. The silver-stained neurons, dendrites and axons were
      considered to have been damaged by the trauma because they were consistently
      absent from control brains. In the "1-day" brains silver-stained dendrites and
      axons had a beaded appearance, indicating an advanced stage of morphopathological
      damage. From details of these findings the following conclusions were drawn: (1)
      trauma can directly induce some kind of morphopathological damage in neurons
      which manifests itself in shrinkage of the soma and tortuosity of appendages as
      well as in type III argyrophilia; (2) different vulnerability of various brain
      areas is likely due to the inhomogeneity of the trauma-induced pressure wave
      propagating through the brain; and (3) the somato-dendritic and axonal domains of
      the neuron are selectively vulnerable to different values of the parameters of
      the intracranial pressure wave.

PMID- 1374203
TI  - Caudate nucleus pathology in Parkinson's disease: ultrastructural and biochemical
      findings in biopsy material.
AB  - Ultrastructural and biochemical properties of caudate nucleus (CN) biopsies in
      two patients with advanced Parkinson's disease (PD) were compared with three CN
      specimens removed during surgery for intracranial tumors. An additional two
      specimens from neurologically intact patients (59 and 86 years old) were removed
      during autopsy (performed 3 and 4 h post mortem, respectively) for electron
      microscopic studies. Dopamine levels in PD were reduced to less than 15% of
      control values. Both PD patients showed frequent dystrophic neurites and
      transsynaptic degeneration of neurons and neuritic processes. These changes were
      not found in CN from the four control individuals. Only a few dystrophic neurites
      were noticed in one 67-year-old control patient. The development of neuroaxonal
      dystrophy in CN is consistent with a dying-back process, probably accompanying
      abnormalities of axonal transport in PD. Transsynaptic degeneration of neurons in
      CN very likely represents a morphological marker of disease severity. The
      occurrence of this change may account for the poor clinical response of patients
      with advanced PD to intracerebral implantation of dopaminergic tissues.

PMID- 1374205
TI  - An immediate light microscopic response of neuronal somata, dendrites and axons
      to contusing concussive head injury in the rat.
AB  - Thirty-four rats were killed by transcardial perfusion fixation 1 min after a
      contusing concussive head injury, and 17 rats 1 day later. From the results
      obtained with a new silver method demonstrating traumatically damaged neuronal
      somata, dendrites and axons the following conclusions were drawn: (1) outside the
      contused territories all features of traumatically induced neuronal argyrophilia
      are similar to those found in non-contusing concussive head injury, as reported
      in an accompanying paper; (2) within contused territories the neuronal
      argyrophilia is abolished by some substance released either from damaged blood
      vessels or damage parenchymal cells, while the neuronal damage otherwise
      underlying the induction of argyrophilia is present; (3) different phenotypes of
      neurons are vulnerable to different values of the parameters of the intracranial
      pressure wave generated by the trauma; (4) some of the neurons may recover from
      the traumatically induced argyrophilic damage; (5) traumatically induced
      inundation of neurons with extracellular tracers, as reported by other authors,
      and somato-dendritic argyrophilia may be different manifestations of one and the
      same phenomenon; and (6) diffuse primary traumatic axonal injury in human
      neuropathology may be closely correlated to axonal argyrophilia.

PMID- 1374206
TI  - A case of pigmentary type of orthochromatic leukodystrophy with early onset and
      globoid cells.
AB  - We report herein a sporadic case of the pigmentary type of orthochromatic
      leukodystrophy with early onset and very rapid clinical course. The patient's
      development was normal until 2 years old, when he experienced visual disturbance.
      Rapid deterioration resulted in death 1.5 years after the onset. Metachromatic
      leukodystrophy, globoid cell leukodystrophy and adrenoleukodystrophy were
      excluded by biochemical assays. Autopsy findings were compatible with the
      diagnosis of the pigmentary type of orthochromatic leukodystrophy. However, there
      were unique findings of severe neuronal loss and the collection of globoid-like
      cells in the interface of the gray matter and the white matter.
      Immunohistochemical staining of myelin basic protein, proteolipid protein and
      galactocerebroside demonstrated that these myelin constituents were equally
      preserved in the posterior column, while absent in the lateral and anterior
      columns of the spinal cord.

PMID- 1374207
TI  - Experimental maxillary sinusitis induced by Bacteroides fragilis. A
      bacteriological and histological study in rabbits.
AB  - Experimental anaerobic maxillary sinusitis was induced in New Zealand White
      rabbits by blocking the ostium and inoculating Bacteroides fragilis, strain NCTC
      9343. The animals were examined histologically and bacteriologically after 5
      days, and 2, 3 and 4 weeks. All the infected sinuses displayed signs of moderate
      or severe inflammation throughout the study period. Ciliary damage and
      desquamation, hyperplasia and metaplasia of the epithelium were characteristic
      features. Furthermore, heavy leukocyte- and, particularly, round cell
      infiltration, fibrosis, periosteal hyperplasia and bone degradation and 
      formation were also frequently encountered. The secretory cell count in the
      epithelium increased, including the regeneration of goblet cells. After 4 weeks
      no obvious recovery could be seen, and the inducing microorganism was re-isolated
      in the majority of cases. In comparison with experimental pneumococcal sinusitis,
      the B. fragilis infection exerts a more prolonged and severe inflammation.

PMID- 1374208
TI  - Distribution of lymphoid cells in tonsillar compartments in relation to infection
      and age. A quantitative study using image analysis.
AB  - The distribution of lymphoid cells in the mantle zone, germinal center,
      interfollicular area, and subepithelial area of the tonsil was evaluated
      quantitatively by image analysis in 66 subjects aged 3 to 66 years. The number of
      Ig-positive cells in the tonsil decreased with advancing years in all
      compartments. This inverse correlation to age was statistically significant for
      IgD-, IgM-, and IgG-positive cells. For T-cells, overall change of each T-cell
      subset with age was smaller than those of Ig-positive cells. An age-related
      marked decline was seen for CD4-positive cells only in the subepithelial area and
      for CD8-positive cells only in the interfollicular area. Ki-67-positive cells,
      cells undergoing active division, were mainly found in the germinal centers and
      also diminished with advancing years. Patients with frequent episodes of
      tonsillitis demonstrated a significant increase of IgD-positive cells and IgG
      positive cells in interfollicular and subepithelial compartments and a decrease
      of CD4-positive T-cells in the germinal centers and subepithelial areas. These
      results suggest that the tonsillar involution with age is immunologically
      associated in all compartments with the decrease of Ig-positive cells and Ki-67
      positive activated cells resulting in a relative increase of T-cell subsets. The
      method of image analysis provides a novel and unique approach for quantitative
      immunohistological study of the tonsil.

PMID- 1374209
TI  - Intrathecal neurokinin A facilitates the spinal nociceptive flexor reflex evoked
      by thermal and mechanical stimuli and synergistically interacts with substance P.
AB  - The neuropeptide neurokinin A was injected intrathecally and its effect on the
      spinal nociceptive flexor reflex was examined. The reflex, which was evoked by
      electrical, thermal or mechanical stimulation of the foot and was recorded from
      the ipsilateral hamstring muscles, was substantially facilitated by 7 pmol
      intrathecally injected neurokinin A. The facilitatory effect of neurokinin A to
      thermal stimulation was, however, significantly stronger than to electrical or
      mechanical stimuli. Furthermore, co-administration of neurokinin A with substance
      P induced a significant synergistic facilitation of the reflex. It is suggested
      that neurokinin A, like substance P, may be released in association with
      activation of polymodal C-nociceptors.

PMID- 1374210
TI  - Chloride-selective channels of large conductance in bovine aortic endothelial
      cells.
AB  - Single-channel currents of an anionic channel in the plasma membrane of cultured
      bovine aortic endothelial cells have been recorded with the patch-clamp
      technique. The channel is selective for chloride over cations, and has an average
      single channel conductance of 382 picosiemens in symmetric 140 millimoles of
      chloride. In addition to the main conductance state it shows well-defined
      subconductance states of about 50, 100, 150 and 200 picosiemens. The channel is
      very active at membrane potentials close to 0 mV, but steps to either positive or
      negative membrane potentials above +/- 20 millivolt lead to a rapid inactivation
      of the channel. Changes in the concentrations of free calcium or adenosine tri
      phosphate on the cytosolic surface do not influence channel activity. The
      chloride channel rarely opens at resting membrane potential, but it may help
      repolarize endothelial cells following depolarizing stimuli.

PMID- 1374211
TI  - Rat liver nodules induced by 2-acetylaminofluorene lose an ability to take up
      indocyanine green in the process of hepatocarcinogenesis.
AB  - Indocyanine green (ICG) was injected into rat liver nodules induced by 2
      acetylaminofluorene (2-AAF) via portal vein. The relationship between ICG
      staining and cell atypism of liver nodules was examined by means of histology and
      DNA flow cytometry. After 2-AAF administration, many small nodules appeared on
      the liver surface. All hyperplastic nodules were ICG stained until 10 weeks after
      the administration, but some nodules were not stained after 14 weeks. ICG-stained
      nodules histologically consisted of benign tissues and borderline lesions, and
      many of them showed "diploidy" in DNA cytometry. ICG-unstained nodules consisted
      of hepatocellular carcinoma (HCCs) and borderline lesions, and many of them
      showed "aneuploidy". In this way, it has been suggested that HCC could derive
      from hyperplastic nodules and that they might lose an ability to take up ICG in
      the process of hepatocarcinogenesis. Immunohistochemical staining for glutathione
      S-transferase alpha (GST-alpha), a carrier protein of ICG in hepatocytes, was
      well correlated with ICG staining in the nodules, suggesting that the loss of ICG
      uptake in HCC was partly due to the decrease of GST-alpha. Moreover, the
      appearance of ICG unstained and aneuploid nodules was significantly inhibited in
      rats which were fed on diet containing Syosaiko-to after the administration of 2
      AAF. Chemopreventive effect of Syo-saiko-to on hepatocarcinogenesis was
      identified.

PMID- 1374212
TI  - Prospects for oral vaccination using recombinant bacteria expressing viral
      epitopes.

PMID- 1374213
TI  - Monoclonal antibody to Pneumocystis carinii. Comparison with silver stain in
      bronchial lavage specimens.
AB  - Monoclonal 3F6 anti-Pneumocystis carinii antibody (MAB-3F6) was used to stain
      cell blocks from 164 bronchial lavage specimens from patients with the acquired
      immune deficiency syndrome (AIDS) and AIDS-related complex and compared with
      slides stained with Grocott's modification of the Gomori methenamine silver
      stain. Pneumocystis organisms were present in 83 of 164 cases using MAB-3F6
      stain, whereas Grocott's modified silver stain demonstrated Pneumocystis
      organisms in 48. MAB-3F6 demonstrated Pneumocystis organisms in 38 cases with
      negative silver stains, whereas silver stain identified Pneumocystis organisms in
      only three MAB-3F6-negative cases. Of 70 patients with clinical Pneumocystis
      pneumonia at the time of the specimen was obtained, 59 had MAB-3F6-positive
      specimens, whereas 39 had organisms detected using Grocott's modified silver
      stain. Of 37 patients without clinically apparent Pneumocystis pneumonia any time
      in their course, 4 had abundant organisms and 33 had negative stains with MAB
      3F6. MAB-3F6 detected Pneumocystis organisms in 22 of 31 cases of Pneumocystis
      pneumonia that had no organisms identified using Grocott's silver stain (X2 =
      5.76, P = 0.016). MAB-3F6 immunochemical staining is a more sensitive method than
      Grocott's modified silver stain to detect Pneumocystis organisms.

PMID- 1374214
TI  - Expression of oncogenic antigen 519 (OA-519) in prostate cancer is a potential
      prognostic indicator.
AB  - Predicting the prognosis of patients with prostate cancer is a clinically
      important problem. Previous studies have indicated that the expression of
      haptoglobin-related protein epitopes in samples of breast cancer in early stages
      was associated with earlier relapses and higher risk for tumor recurrence.
      Oncogenic antigen 519 (OA-519) is the new marker designation for molecules
      expressing haptoglobin-related protein epitopes. The objective of this
      immunohistochemical study was to examine OA-519 expression in prostate cancer
      samples and its relationship to the established prognostic indicators of tumor
      grade, tumor volume, and clinical stage. Forty-two consecutive tissue samples of
      prostate adenocarcinoma were examined using an affinity-purified anti-OA-519
      antibody. Twenty specimens (48%) tested positive, whereas 22 (52%) tested
      negative. No staining was observed in normal or hyperplastic prostate tissue.
      Staining occurred in 6 of 9 (67%) grade III, 14 of 23 (61%) grade II, and in none
      of 10 (0%) grade I cases (I vs. II and/or III: Fisher exact test, P less than
      0.006). Twenty-three of the 42 samples were transurethral resection specimens
      with cancer; 11 (48%) of these tested positive. The mean percentage of tissue
      chips with tumor, a measure of tumor volume, was significantly higher in the
      positive group (57%) than in the negative group (15%) (P = 0.004). The proportion
      of positively stained cases increased with advancing clinical stage, with 25% of
      Stage A cases expressing OA-519, and 46%, 67%, and 64% of Stages B, C, and D,
      respectively, expressing OA-519. OA-519 expression correlates with higher tumor
      grades, larger tumors, and possibly with advanced stage, and thus, it is
      potentially of prognostic value in prostate cancer.

PMID- 1374215
TI  - Malignant lymphoma of the breast. Immunologic type and association with
      lymphocytic mastopathy.
AB  - Clinical and pathologic findings in 19 cases of primary non-Hodgkin's lymphoma of
      the breast collected from several hospitals in Japan were reviewed. All patients
      were women (median age, 45 years) and they usually had breast masses that had
      recently become enlarged. The sites of the lesions were the right breast in eight
      cases, the left breast in eight, and both breasts in one. The locations of two
      masses were unknown. Lymphoma recurred in the opposite breast in three cases 14,
      23, and 23 months after surgery. Histologically, diffuse large cell lymphoma was
      the most common form of disease (63%). One lesion was a follicular lymphoma. The
      so-called lymphoepithelial lesion, a characteristic finding for mucosa-associated
      lymphoid tissue type lymphomas, was observed in eight cases (42%).
      Immunohistochemical analysis revealed that all but two tumors were of B-cell
      type; such findings confirmed morphologically based conclusions. Histologic and
      immunohistochemical evidence of lymphocytic mastopathy, a recently described
      autoimmune disease of the breast, was found in most of the cases. Formation of
      lymphoid follicles in or around the tumors was found in five cases (26%). Based
      on these findings, it is suggested that most mammary lymphomas are B-cell tumors
      and they may be associated with coexisting or antecedent lymphocytic mastopathy.

PMID- 1374216
TI  - Tdt-positive ALL-L3.

PMID- 1374217
TI  - Immunocytochemical identification of proliferative hepatocytes using monoclonal
      antibody to proliferating cell nuclear antigen (PCNA/cyclin). Comparison with
      immunocytochemical staining for DNA polymerase-alpha.
AB  - The authors investigated whether immunocytochemical staining with a monoclonal
      antibody to proliferating cell nuclear antigen (PCNA/cyclin) could be used to
      identify proliferative hepatocytes in frozen sections fixed in a mixture of
      periodate, lysine, and 2% paraformaldehyde. Paraffin sections also were used,
      which were fixed in 10% formaldehyde. Specimens of liver tissue were obtained
      from 27 patients with various hepatic diseases. Hepatocytes that were positive
      for PCNA/cyclin were observed in both types of substrate specimens. In acute
      hepatitis and chronic active hepatitis, most hepatocytes that were labeled for
      PCNA/cyclin were located near necrotic foci. However, in cirrhosis, they were
      detected most often near fibrotic septa; the number of immunoreactive cells
      varied greatly in different areas of tissue sections in such cases. In
      hepatocellular carcinoma, many PCNA/cyclin-positive tumor cells were seen
      throughout the neoplasms. Hepatocytes that were positive for DNA polymerase-alpha
      showed a similar distribution pattern in serial sections of study cases.

PMID- 1374218
TI  - Immunohistochemical c-erbB-2 protooncogene expression and nuclear DNA content in
      human mammary carcinoma in situ.
AB  - Immunohistochemical c-erbB-2 proto-oncogene expression and nuclear DNA
      distribution patterns were assessed in 119 formalin-fixed paraffin-embedded
      surgical specimens of human mammary carcinomas in situ (CIS). The series
      consisted of 107 ductal carcinomas in situ (DCIS), 9 lobular carcinomas in situ,
      and 3 cases of Paget's disease of the nipple. Nuclear DNA distribution patterns
      were assessed by image cytometric analysis of histopathologically identified cell
      nuclei. Fifty-one of 107 (48%) DCIS were immunoreactive for c-erbB-2, whereas
      specific cell membrane staining was absent in lobular carcinomas in situ. The
      neoplastic cell nuclei of 46 CIS (39%) were of DNA diploid type, and 73 CIS (61%)
      contained aneuploid nuclear DNA. Among various histopathologic subtypes of DCIS,
      significant differences in c-erbB-2 immunoreactivity and nuclear ploidy were
      observed. DCIS of the comedo type most often were c-erbB-2 positive and exhibited
      aneuploid nuclear DNA histograms. DCIS of micropapillary type was the second most
      frequently reactive c-erbB-2 expression, and aneuploidy were less common in
      solid, cribriform, and papillary DCIS. The results of the current study indicate
      that immunohistochemical expression of the c-erbB-2 proto-oncogene product is
      closely related to the histopathologic subtype and the nuclear DNA content of
      mammary CIS. Examples of CIS that are c-erbB-2 immunoreactive and DNA aneuploid
      seem to have a significantly higher risk for the subsequent development of
      infiltrating mammary carcinoma.

PMID- 1374219
TI  - Immunoreactivity for c-erbB-2 oncopeptide in benign and malignant diseases of the
      liver.
AB  - The immunohistochemical detection of the c-erbB-2 oncopeptide (p185erbB2) has
      been shown to be a valid marker for over-expression of this oncogene. To evaluate
      the possible relevance of gene expression to the proliferation of hepatocytes and
      bile ducts in human disease, the authors applied a monoclonal anti-p185 antibody
      to formalin-fixed, paraffin-embedded tissues from 67 examples of benign
      proliferative and neoplastic hepatic lesions and fetal liver. Focal membrane
      based reactivity for the oncopeptide was detected on tumor cells in two of eight
      hepatocellular carcinomas and on tumor cells and adjacent bile ducts and
      hepatocytes in four of six cholangiocarcinomas. Each of the latter four lesions
      were in patients with primary sclerosing cholangitis. No reactivity was obtained
      in examples of hepatoblastoma, mixed cholangiocarcinoma-hepatocellular carcinoma,
      bile duct adenoma, or hepatocellular adenoma. Weak staining for p185erbB2 also
      was seen in two of seven cases of (sub)massive hepatic necrosis and two examples
      of postnecrotic cirrhosis, all of which were secondary to either hepatitis B or C
      virus infection. No other benign proliferative lesions were labeled by the anti
      p185 antibody, including cases of chronic allograft rejection, necrosis secondary
      to hepatic artery thrombosis, metabolic-associated and nonmetabolic-associated
      cirrhosis, focal nodular hyperplasia, and nodular regenerative hyperplasia. The
      authors' results indicate that c-erbB-2 may be amplified in specific neoplastic
      and hepatitis B virus and hepatitis C virus infectious lesions of liver. The
      authors postulate that: (1) c-erbB-2 immunoreactivity may be a marker for
      malignant transformation in primary sclerosing cholangitis; and 2) overproduction
      of p185erbB2 may be an epiphenomenon of hepatitis B virus or hepatitis C virus
      infection.

PMID- 1374220
TI  - A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus
      monkeys.
AB  - A major factor in the pathogenesis of human cerebral malaria is blockage of
      cerebral microvessels by the sequestration of parasitized human red blood cells
      (PRBC). In vitro studies indicate that sequestration of PRBC in the microvessels
      is mediated by the attachment of knobs on PRBC to receptors on the endothelial
      cell surface such as CD36, thrombospondin (TSP), and intercellular adhesion
      molecule-1 (ICAM-1). However, it is difficult to test this theory in vivo because
      fresh human brain tissues from cerebral malarial autopsy cases are not easy to
      obtain. Although several animal models for human cerebral malaria have been
      proposed, none have shown pathologic findings that are similar to those seen in
      humans. In order to develop an animal model for human cerebral malaria, we
      studied brains of rhesus monkeys infected with the primate malaria parasite,
      Plasmodium coatneyi. Our study demonstrated PRBC sequestration and cytoadherence
      of knobs on PRBC to endothelial cells in the cerebral microvessels of these
      monkeys. Cerebral microvessels with sequestered PRBC were shown by
      immunohistochemical analysis to possess CD36, TSP, and ICAM-1. These proteins
      were not evident in the cerebral microvessels of uninfected control monkeys.
      Thus, our study indicates, for the first time, that rhesus monkeys infected with
      P. coatneyi can be used as a primate model to study human cerebral malaria. By
      using this animal model, we may be able to evaluate strategies for the
      development of vaccines to prevent human cerebral malaria.

PMID- 1374221
TI  - Prevalence of antibody to hepatitis C virus in Japanese schoolchildren:
      comparison with adult blood donors.
AB  - A total of 1,442 schoolchildren in the Matsumoto City area were investigated for
      the prevalence of hepatitis virus-related serum markers, including antibody to
      hepatitis C virus (anti-HCV) and an abnormal serum transaminase level. Despite
      the large number of children tested, none was positive for anti-HCV antibodies or
      had been diagnosed as having viral hepatitis. The prevalence of anti-HCV
      antibodies in children and adult blood donors in the same area increased
      significantly with age from 0% in the 6-15-year-old group to 1.14% in the 50-65
      year-old group (P less than 0.001). Our results indicate that even if only the
      enzyme-linked immunosorbent assay results confirmed by the recombinant immunoblot
      assay are considered positive, the prevalence in children is significantly lower
      than that in blood donors (P less than 0.05). Six children were healthy carriers
      of hepatitis B virus (HBV); all had been born to carrier mothers. These results
      indicate that apparently healthy schoolchildren in Japan have a low exposure to
      HCV infection.

PMID- 1374222
TI  - Effective palliative treatment of metastatic carcinoid tumors with intra-arterial
      chemotherapy/chemoembolization combined with octreotide acetate.
AB  - Survival in patients with metastatic carcinoid tumors is dependent on control of
      tumor growth and adequate palliation of vasoactive amine-induced symptoms of
      flushing, diarrhea, wheezing, and valvular heart disease. Eight patients with
      carcinoid tumors metastatic to the liver were treated with long-term octreotide
      acetate therapy (100 to 500 micrograms three times a day), intra-arterial 5
      fluorouracil infusion (2 g/day x 5 days), and hepatic tumor chemoembolization.
      All eight patients became asymptomatic and have remained so with a mean follow-up
      duration of 22 months from the time of first infusion. Following institution of
      subcutaneous octreotide acetate, intra-arterial infusion, and tumor
      chemoembolization, all patients are alive with a mean survival of 40 months from
      the time of diagnosis of carcinoid syndrome (range: 2 to 108 months). Four
      patients had greater than a 50% decrease in tumor size after therapy (mean follow
      up duration: 10.6 months), and the other four patients have had stable disease
      after institution of therapy. It appears that combinations of long-term
      subcutaneous administration of octreotide acetate, intra-arterial 5-fluorouracil,
      and tumor chemoembolization effectively control progressive liver metastasis and
      provide excellent symptomatic palliation in patients with hepatic metastasis from
      functional carcinoid tumors.

PMID- 1374223
TI  - Inhibition of cephalic neural tube closure by 5-azacytidine in neurulating rat
      embryos in vitro.
AB  - Head-fold stage rat embryos (9.5 days of gestation) were cultured for 48 h in rat
      serum with or without 0.8 microM 5-azacytidine. Incomplete closure of the
      cephalic neural tube was observed in 5-azacytidine-treated embryos cultured for
      48 h (25-somite stage). Control embryos showed complete fusion of cephalic neural
      folds at 33 h (16-somite stage) in culture. Drug administration or removal
      experiments revealed that embryos were sensitive to 5-azacytidine during 6-12 h
      of culture (three to five somite stages). Electron microscopical studies
      indicated that the arrangement and fine structure of cephalic neuroepithelial
      cells were almost the same in control and treated embryos. There was no
      significant difference in DNA and protein contents between control and treated
      embryos cultured for 36 h. Immunocytochemical observations using 5-methylcytosine
      specific antibody revealed that the staining of neuroepithelial cells in the
      median part of the transversely sectioned cephalic neural plate, and of
      mesenchymal cells near the apices of the plate, was suppressed by 5-azacytidine.
      These results suggest that DNA methylation of these cells plays an important role
      in closure of the cephalic neural tube.

PMID- 1374224
TI  - Purification and characterization of soluble forms of human and rat stem cell
      factor recombinantly expressed by Escherichia coli and by Chinese hamster ovary
      cells.
AB  - Stem cell factor (SCF) is a novel, early-acting hematopoietic factor. It was
      isolated from the medium of a rat cell line in a soluble, processed form (Zsebo
      et al., 1990, Cell 63, 195). The cloned human and rat genes encode the soluble
      form plus additional C-terminal amino acids including a hydrophobic transmembrane
      domain (Martin et al., 1990, Cell 63, 203). We have recombinantly expressed forms
      of human and rat SCF corresponding to the soluble, processed form in Escherichia
      coli and in Chinese hamster ovary (CHO) cells. After expression in E. coli,
      folding and oxidation of the SCF polypeptides are required. The SCFs expressed in
      CHO cells are secreted into the medium in active state and, like the natural SCF,
      are glycosylated. Purification of the recombinant SCFs is described. Biological
      and biochemical characterization includes activity toward responsive human and
      mouse cell lines, N-terminal amino acid sequences, disulfide bond linkages, and
      sites of glycosylation.

PMID- 1374225
TI  - Dermal granulomatous inflammation to cornified cells. Significance near cutaneous
      squamous cell carcinoma.
AB  - BACKGROUND: Discrimination of benign from malignant is fundamental to accurate
      histologic diagnosis. This article describes a series of nine patients with
      cutaneous squamous cell carcinoma who were noted to have in the vicinity of their
      neoplasm seemingly benign but biologically significant dermal granulomatous
      inflammation to cornified cells (GRC). OBSERVATIONS: Two patients were reported
      as having this finding alone on incisional biopsy specimens only to have
      subsequent biopsy specimens demonstrate bona fide malignant neoplasms. On Mohs'
      frozen sections, four patients were noted to have GRC without concomitant tumor
      and four patients had GRC admixed with tumor. Two patients who demonstrated GRC
      but no neoplasm on final Mohs' sections had development of recurrent neoplasm
      after the initial procedure. CONCLUSIONS: In the setting of suspected or proved
      cutaneous squamous cell carcinoma, GRC signifies the presence of viable neoplasm
      and warrants additional tissue resection.

PMID- 1374226
TI  - Congenital retinal dystrophies: a study of early cognitive and visual
      development.
AB  - The reported incidence of mental retardation in Leber's congenital amaurosis has
      varied from 10% to 87%. There has been no review of the estimate since it became
      possible to delineate an increasing number of diagnostic subcategories. In this
      study, the visual and cognitive development of 38 children with congenital
      retinal dystrophies has been followed up prospectively. Children with associated
      disorders in other systems and those with central nervous system malformations or
      degenerations were significantly more likely to have learning disability than
      those without additional medical problems. Most subgroups made little or no
      visual progress with the exception of the group with associated hypoplasia of the
      cerebellar vermis. The study highlights the importance of using the specialised
      techniques now available to delineate fully the visual diagnosis and paediatric
      perspective because of their relevance to cognitive and visual prognosis.

PMID- 1374227
TI  - Localisation and characterisation of substance P binding to human synovial tissue
      in rheumatoid arthritis.
AB  - The neuropeptide substance P is found in perivascular and free unmyelinated nerve
      fibres in human synovial tissue. Quantitative receptor autoradiography was used
      to show specific, high affinity (Kd = 0.75 (0.21), nmol/l (mean (standard error
      of the mean)), low capacity (Bmax = 27.8 (7.9) amol/mm2) binding sites for
      substance P Bolton Hunter-labelled with iodine-125 localised to vascular
      endothelial cells in human synovial tissue. The binding could be saturated, was
      reversible, and was dependent on the magnesium concentration. Unlabelled
      substance P and neurokinin A competitively inhibited specific binding with 50%
      inhibition at concentrations of 1.25 (0.21) and 175 (29) nmol/l respectively.
      Neurokinin B (mumol/l) and calcitonin gene related peptide (1 mumol/l) did not
      inhibit binding. These binding sites show characteristics of the neurokinin 1
      tachykinin receptor subtype. This provides further evidence that substance P may
      play a part in the vascular control of human synovium and may influence
      inflammatory processes in joints.

PMID- 1374228
TI  - Symptomatic choledochoceles in adults. Endoscopic retrograde
      cholangiopancreatography recognition and management.
AB  - During a 2-year interval, we identified 10 patients with symptoms of
      pancreaticobiliary disorders and small choledochoceles by endoscopic retrograde
      cholangiopancreatography. Patients ranged from 36 to 89 years of age. Eight were
      female. Seven presented with recurrent, acute pancreatitis, two presented with
      biliary colic, and one presented with cholangitis. Dilated common bile ducts were
      seen in four patients, and no other biliary lesions were demonstrated in any
      patients. Five patients were shown to have normal gallbladders by
      ultrasonographic or computed tomographic criteria. Choledochoceles were
      identified endoscopically as a bulge above or involving the ampulla. Diagnosis
      was confirmed by cholangiography. All patients underwent successful unroofing of
      the choledochocele and sphincterotomy of the common bile duct. One pancreatic
      sphincterotomy was performed for pancreatic ductal obstruction. We encountered no
      complications. Hospital stays ranged from 1 to 4 days. Follow-up intervals ranged
      from 2 to 20 months. At this time, no patients have had any recurrence of
      symptoms, and none has required rehospitalization or surgery.

PMID- 1374229
TI  - [Advances in the fundamentals and therapeutic use of immunosuppressive agents].

PMID- 1374230
TI  - Expression of renal organic cation transporter in Xenopus laevis oocytes.
AB  - The expression of the organic cation transport system of rat renal proximal
      tubules has been studied in Xenopus laevis oocytes injected with poly(A)+ RNA
      from the rat renal cortex. The effectiveness of the technique was confirmed by
      examining expression of the Na+/D-glucose co-transporter. Compared with water
      injected and non-injected oocytes, the injection of total poly(A)+ RNA resulted
      in about a 3-fold increase in tetraethylammonium (TEA) uptake activity. TEA
      uptake by poly(A)(+)-RNA-injected oocytes was time-dependent and was inhibited by
      cimetidine and HgCl2, but not by p-aminohippurate. After size-fractionation on a
      sucrose density gradient, a 1.4-2.4 kb poly(A)+ RNA fragment was identified that
      expressed the organic cation transport system in oocytes. These results
      demonstrate that the renal organic cation transporter was expressed in oocytes
      and that this expression system can provide an effective assay procedure for
      cloning of the organic cation transporter.

PMID- 1374231
TI  - Cyclic AMP-independent secretion of mucin by SW1116 human colon carcinoma cells.
      Differential control by Ca2+ ionophore A23187 and arachidonic acid.
AB  - The regulation of mucin secretion by SW1116 human colon carcinoma cells has been
      studied using monoclonal antibody 19-9, which has previously been used to detect
      mucin in the serum of cancer and cystic fibrosis patients. We found that SW1116
      cells constitutively secrete considerable amounts of mucin as the predominant
      glycoprotein. The secretion of mucin by these cells is independent of cyclic AMP
      levels, but can be further stimulated by the Ca2+ ionophore A23187. However,
      arachidonic acid and its metabolites inhibit mucin secretion. Electron microscope
      studies reveal that the mucin is located near the plasma membrane as well as in
      vesicular and lysosome-like structures. However, the secretion pathway of mucin
      is different than that of the lysosomal contents, since arachidonic acid, while
      inhibiting mucin secretion, actually activates the secretion of the lysosomal
      enzyme beta-glucuronidase. We suggest that the mechanism of mucin secretion by
      SW1116 cells occurs by a pathway different from common exocytosis, and possibly
      by more than one pathway. The response of mucin secretion by SW1116 cells to
      common secretagogues resembles that of epithelial cells obtained from cystic
      fibrosis patients. Thus SW1116 cells are an especially interesting system for
      studying processes related to pathological states associated with excessive
      constitutive secretion of mucin.

PMID- 1374232
TI  - Critical evaluation of a theory of molecular recognition using human insulin-like
      growth-factor-I fragment 21-40 and its complementary peptide.
AB  - Using solid-phase methods we have synthesized human insulin-like-growth-factor-I
      (IGF-I) fragment 21-40 (IGF-I 21-40) and the peptide derived from the 5'----3'
      translation of the complementary nucleic acid of this peptide, 'I-FGI 20-40' (the
      complementary peptide). According to a recently proposed theory of molecular
      recognition, these two peptides should bind specifically to each other. We have
      tested this theory by using both solid- and solution-phase direct-binding assays
      for this complementary-peptide pair. We have also investigated the ability of I
      FGI 20-40 to interfere with native IGF-I binding during radioimmunoassay
      (r.i.a.), radio-receptor (r.r.a.) assay and ligand-blot analysis of IGF-binding
      proteins. We have obtained no evidence of any interaction between IGF-I 21-40 and
      I-FGI 20-40 in either solid- or solution-phase assays. In addition, I-FGI 20-40
      does not interfere in the assays used to detect IGF-I binding antibodies
      (r.i.a.), receptors (r.r.a.) or binding proteins (ligand blots). Our data
      therefore question the universality of this particular theory of molecular
      recognition.

PMID- 1374234
TI  - Tumor necrosis factor-alpha pretreatment is protective in a rat model of
      myocardial ischemia-reperfusion injury.
AB  - We have demonstrated that tumor necrosis factor-alpha (TNF-alpha) pretreatment
      protected the rat heart from ischemia-reperfusion injury. This effect was
      monitored by assaying for lactate dehydrogenase (LDH), an enzyme whose release
      correlates with loss of cell membrane integrity. Intact hearts removed from rats
      pretreated with TNF-released significantly lower amounts of LDH compared to
      control hearts after 20 min. of total global ischemia followed by reperfusion.
      Hearts from TNF-alpha-pretreated animals contained higher levels of manganous
      superoxide dismutase (MnSOD) mRNA than hearts from untreated rats. Because oxygen
      free radicals have been implicated as a major cause of reperfusion damage and the
      function of MnSOD is to detoxify superoxide anions in the mitochondria, a
      possible protective mechanism for TNF-alpha may be to induce expression of MnSOD
      in the heart and thus confer resistance to oxygen free radicals generated during
      reperfusion.

PMID- 1374233
TI  - Comparison of L-selectin and E-selectin ligand specificities: the L-selectin can
      bind the E-selectin ligands sialyl Le(x) and sialyl Le(a).
AB  - The L- and E-selectins are leukocyte and endothelial cell surface molecules which
      mediate leukocyte-endothelial cell adhesion by interacting with carbohydrate
      ligands. In the present study we find that L-selectin, like E-selectin, can
      interact with synthetic neoglycoproteins containing Sialyl Le(x) (Neu5Ac alpha 2
      3Gal beta 1-4[Fuc alpha 1-3]GlcNAc beta-R), or Sialyl Le(a) (Neu5Ac-alpha 2-3Gal
      beta 1-3[Fuc alpha 1-4]GlcNAc beta-R). Additionally, both the E-selectin and L
      selectin can bind the peripheral lymph node addressin, a high endothelial venule
      ligand for L-selectin. Despite overlapping interactions, the L- and E-selectins
      discriminate between their native ligands. The peripheral lymph node addressin is
      a preferential ligand for L-selectin; and furthermore, L-selectin expressing
      cells do not interact detectably with the cutaneous lymphocyte antigen, a native
      glycoprotein ligand for E-selectin found on a subset of lymphocytes associated
      with the skin.

PMID- 1374235
TI  - Developmental expression of ornithine and S-adenosylmethionine decarboxylases in
      mouse brain.
AB  - The activities of the two key enzymes in mammalian polyamine synthesis, ornithine
      decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) in mouse
      brain show distinct, but inverse, changes during ontogeny. The level of ODC
      activity is about 70 fold higher at the time of birth than in the adult mouse,
      whereas AdoMetDC activity is very low after birth and increases as the brain
      matures. The correlation between the changes in enzyme activities and in the
      levels of the corresponding mRNAs diminishes dramatically during development. The
      increase in AdoMetDC mRNA level exceeds the increase in enzyme activity by 100%.
      Whereas ODC mRNA level falls initially, in concert with decreasing enzyme
      activity, but then shows an abrupt rise to a very high level during the late
      period of brain maturation while the enzyme activity continues to decrease to an
      almost undetectable level. These data suggest the development-dependent
      appearance of post-transcriptional regulation mechanisms.

PMID- 1374236
TI  - Isolation of a cDNA that encodes a novel granulocyte N-formyl peptide receptor.
AB  - A cDNA of 1650 base pairs was isolated by screening an HL-60 granulocyte library
      with an N-formyl peptide receptor (NFPR) cDNA probe under low stringency
      conditions. The cDNA encodes a protein of 351 amino acids tentatively named FPR2,
      with a calculated molecular weight of 39 kDa. Sequence analysis revealed that
      FPR2 is 69% identical in sequence to the human NFPR and shares extensive homology
      to several other chemoattractant receptors. FPR2 expressed in transfected cells
      mediated formyl peptide-stimulated calcium mobilization at micromolar
      concentrations of ligand. FPR2 messenger is detected in granulocytic HL-60 cells,
      but not in undifferentiated HL-60 cells. These findings suggest that FPR2 is a
      novel receptor for formyl peptide ligand and a new member of the chemoattractant
      receptor gene family.

PMID- 1374237
TI  - Structure of the human alpha-2 macroglobulin gene and its promotor.
AB  - The human alpha 2-macroglobulin gene was isolated in five overlapping clones. The
      gene spans approx. 48 kb and consists of 36 exons, from 21 to 229 bp in size and
      with consensus splice sites. Intron sizes range from 145 bp to 7.5 kb. The alpha
      2M gene is a single copy gene in the human genome. A sequence polymorphism within
      the bait domain, coding for an Arg to His substitution within the primary
      cleavage site for trypsin, was identified in 1 of 132 individuals tested so far.
      Three transcription initiation sites have been identified in liver by primer
      extension and RNase protection assays. The most proximal, major site (+1) is
      preceded by a TATA-like structure (ATAAA) at -26 bp. Only 2 mRNA species were
      found in uterus and in cultured lung fibroblasts, while alpha 2M is not expressed
      to a detectable level in skin fibroblasts. The far distal transcription
      initiation site which is preceded by an intact TATA box and a potential HP-1
      binding site is thus specific for liver.

PMID- 1374238
TI  - Isolation and sequencing of a cDNA clone encoding the 85 kDa human lysosomal
      sialoglycoprotein (hLGP85) in human metastatic pancreas islet tumor cells.
AB  - A full length cDNA for a human lysosomal membrane sialoglycoprotein (hLGP85) was
      isolated as a probe of the cDNA of rat LGP85 (rLGP85) from the cDNA library
      prepared from total mRNA of QGP-1NL cells, a human pancreatic islet tumor cell
      with a high metastatic activity. The deduced amino acid sequence shows that
      hLGP85 consists of 478 amino acid residues (MW. 54,289). The protein has 10
      putative N-glycosylation sites and 2 hydrophobic regions at the NH2- and near the
      COOH-termini, respectively. Thus, both domains probably constitute putative
      transmembrane domains. It exhibits 86% and 79% sequence similarities in amino
      acids and nucleic acids to rat lysosomal membrane sialoglycoprotein (rLGP85),
      respectively. The protein contained the short cytoplasmic tail at the COOH
      terminus which does not form the glycine-tyrosine sequence (GY motif), the so
      called lysosomal targetting signal.

PMID- 1374239
TI  - Differential distribution of nitric oxide synthase between cell fractions
      isolated from the rat gastric mucosa.
AB  - Cells isolated from the rat gastric mucosa were resolved into two fractions on a
      percoll density gradient, and into five fractions using counterflow
      centrifugation (elutriation). Ca(2+)-dependent nitric oxide synthase (NOS)
      activity was found in the high density percoll fraction but not in the parietal
      cell enriched low density fraction. This activity was inhibited by NG-monomethyl
      L-arginine with an IC50 of 3.7 microM. Cells in the elutriator fraction rich in
      mucous-epithelial cells exhibited the highest NOS activity, while the smaller
      cell fractions had no detectable NOS yet had the highest basal release of
      prostaglandin E2. The parietal cell enriched elutriator fraction again had low
      NOS activity. The activity of a constitutive NOS in the mucous-cell fraction may
      indicate a role of NO in the regulation of epithelial cell integrity or
      secretion.

PMID- 1374240
TI  - cDNA cloning of a human 25 kDa FK506 and rapamycin binding protein.
AB  - The abilities of FK506 and rapamycin to block distinct signal transduction
      pathways are mediated by soluble binding proteins. Previously, a family of these
      receptors has been recognized that includes a 25 kDa protein, FKBP25. We now
      report the isolation of a cDNA for FKBP25 from a human hippocampal cDNA library
      by oligonucleotide screening. The nucleotide sequence reveals an open reading
      frame that encodes a 224 amino acid polypeptide. Human FKBP25 shows 97% amino
      acid identity with bovine FKBP25 and 62% homology with human FKBP12.

PMID- 1374241
TI  - Hypotonic solution increases the slowly activating potassium current IsK
      expressed in xenopus oocytes.
AB  - A slowly activating potassium current was expressed in Xenopus oocytes by
      injection of RNA transcribed from a rat kidney cDNA clone. Hypotonic solutions
      (160 mOsmol/l; control was 220 mOsmol/l) increased the current by increasing the
      rate of activation and by decreasing the depolarization needed to activate the
      current. This effect of hypotonicity was not observed in calcium-free solution,
      but was unaffected by staurosporine or the calmodulin antagonist W7. Cytochalasin
      D reduced the current and prevented the increase by hypotonic solution. The
      results suggest that the increase in this potassium current by hypotonic solution
      might result from calcium entry and changes in the actin network.

PMID- 1374242
TI  - c-myc expression is down-regulated by cell-cell and cell-extracellular matrix
      contacts in normal hepatocytes, but not in hepatoma cells.
AB  - Primary culture of adult rat hepatocytes resulted in marked increase of c-myc
      expression within a few hours. The high level of c-myc mRNA was maintained
      throughout culture on collagen-coated dishes, but decreased greatly with time
      during culture on collagen-gel or matrigel. Expression of c-myc was also down
      regulated at high cell density. The decrease in its expression appeared closely
      related to inhibitions of DNA synthesis and cell spreading. In contrast, hepatoma
      H4TG cells showed a high level of c-myc expression which was not affected by
      culture on any extracellular matrices examined or by the cell density. These
      results suggest that up-regulation of expression of the c-myc gene is linked to
      G0 to G1 transition during cell cycle progression, which in normal hepatocytes is
      strictly regulated by cell-cell and cell-extracellular matrix interactions, but
      that this control mechanism is defective in malignant hepatic tumor cells.

PMID- 1374243
TI  - Rat KC cDNA cloning and mRNA expression in lung macrophages and fibroblasts.
AB  - We have isolated and sequenced overlapping cDNA clones for rat KC*. The 0.93 kb
      cDNA has a single open reading frame of 288 nucleotides, and substantial sequence
      identity with the platelet-factor 4 family members mouse KC, hamster gro, and
      human gro. Using cloned cDNA as a probe, expression of KC mRNA in lavaged rat
      alveolar macrophages (AMs) increased after lipopolysaccharide (LPS) treatment. We
      also studied expression in vitro by a rat fetal lung fibroblast cell line, RFL-6.
      Expression of KC mRNA in RFL-6 cells increased after treatment with interleukin 1
      or with conditioned medium from rat AMs treated with LPS.

PMID- 1374244
TI  - Heterogeneity of 3'untranslated region of bovine acidic FGF transcripts.
AB  - A bovine aFGF genomic clone (14.2 Kb) has been isolated and characterized. This
      clone contains exons 2 and 3 interrupted by 6.7 Kb long intron. Exon 3 contains
      part of the coding region and the 3' untranslated region (3'UTR). Two overlapping
      cDNA clones specific for this 3'UTR have been isolated from bovine retina cDNA
      libraries or after amplification of RNA by the RACE technique. Analysis of these
      clones and RNAse protection assay demonstrate alternative termination of aFGF
      transcripts giving rise to differently sized 3'UTR of 2.5 Kb and at least 3.9 Kb.
      The sequence of these long 3'UTR is highly conserved among species (70% identity
      between human and rat) which suggests an important role for aFGF expression.

PMID- 1374245
TI  - Interleukin-6 down regulates the expression of transcripts encoding cytochrome
      P450 IA1, IA2 and IIIA3 in human hepatoma cells.
AB  - Effects of human interleukin-6 (hIL-6), the major acute phase inducer, on the
      expression of transcripts encoding cytochrome P450s were examined in human
      hepatoma-derived cells. Using reverse-transcription polymerase chain reaction, it
      was demonstrated that three hepatoma cell lines, HepG2, HepG2f and Hep3B, express
      P450 mRNAs encoding IA1, IA2 and IIIA3, the major P450 isozymes involved in
      carcinogen metabolism, and that they also show induction responses to treatment
      with their specific inducers. When hepatoma cells were treated with hIL-6, the
      levels of IA1, IA2 and IIIA3 mRNAs were markedly suppressed. These findings
      suggest that significant down regulation of cytochrome P450s may occur during the
      acute phase reaction, which may result in alterations in drug biotransformation.

PMID- 1374246
TI  - cDNA sequence and heterologous expression of the human neurokinin-3 receptor.
AB  - Functional cDNA clones encoding the human neurokinin-3 receptor were isolated
      from human brain mRNA. The cloned human neurokinin-3 receptor was expressed in
      COS cells and Xenopus oocytes, where peptide binding affinity and intracellular
      effector activation were determined. Neurokinin B is the most potent agonist,
      followed by eledoisin, substance K and substance P. The binding affinities of
      these peptides at the human neurokinin-3 receptor differ quantitatively from the
      rat receptor, implying a functional consequence of the sequence divergence
      between the two species. Heterologous expression in oocytes revealed that, unlike
      the neurokinin-1 receptor, the efficacy of ion channel activation mediated by the
      neurokinin-3 receptor does not approximate the binding affinity. The heterologous
      expression of the human neurokinin-3 receptor will facilitate further
      investigation into its biochemical functions.

PMID- 1374247
TI  - Contribution of the p51 subunit of HIV-1 reverse transcriptase to enzyme
      processivity.
AB  - Human immunodeficiency virus Type I reverse transcriptase is active as either the
      homodimer (p66/p66) or the heterodimer (p66/p51). Purified recombinant p66 and
      p51 expressed in yeast were reconstituted in the presence of 60 mM sodium
      pyrophosphate to enhance dimer formation. Comparison of the processivity of these
      two active reconstituted forms shows that the heterodimer is more processive than
      the homodimer with a cycle almost twice as long as judged by assays utilizing
      poly (U,G) as a challenger to primer-template. Binding assays demonstrated that
      the heterodimer has a higher affinity for primer-template than the homodimer and
      that the p51 subunit has an affinity equal to that of the heterodimer. These
      results suggest that the p51 subunit functions to increase processivity in the
      heterodimer.

PMID- 1374248
TI  - Abrogation of adriamycin toxicity in vivo by cycloheximide.
AB  - The processes involved in cell killing by Adriamycin (ADR) and other agents that
      interact with topoisomerase II are unclear. To investigate the mode of ADR
      cytotoxicity in vivo, we have investigated the effects of the protein synthesis
      inhibitor, cycloheximide (CH), on cell killing by ADR in the murine intestinal
      tract. We have used morphological criteria to assay the cell death. ADR rapidly
      induces cell death in this tissue that has the morphology of apoptosis or
      programmed cell death. CH, when administered immediately after ADR, reduced the
      incidence of cell death by approximately 81% at 3 hr and approximately 51% at 6
      hr after treatment. The inhibitor was only effective when administered within 0.5
      hr of ADR suggesting that critical events leading to cell death may occur during
      this period. The inhibitor did not interfere with the ADR uptake or retention.
      Significant positive correlation was observed between protein and DNA synthesis
      inhibition (as measured by precursor uptake) and apoptosis inhibition. CH delayed
      progression of cells through all phases of the cell cycle except mitosis.
      However, ADR also had a similar effect, suggesting that progression through the
      cell cycle is not necessary for the expression of apoptosis. The effectiveness of
      CH in apoptosis inhibition, even when administered 0.5 hr after the ADR, coupled
      with the rapid uptake of ADR by the intestinal epithelium suggests that the mode
      of inhibition is unlikely to be modulation of cellular targets of ADR such as
      topoisomerase II or inhibition of formation of ADR-topoisomerase II complex.
      These data indicate that topoisomerase II-interacting agents such as ADR may
      induce apoptosis; the processes leading to cell death in this situation are
      thought to be gene dependent and require protein synthesis for their expression.
      Thus, the cytoprotective effect of CH may be due directly to the inhibition of
      protein synthesis.

PMID- 1374250
TI  - Molecular evidence for the presence of chlamydia in the synovium of patients with
      Reiter's syndrome.
AB  - OBJECTIVE: There is much evidence indicating that chlamydial antigens in the
      synovium may be critical in the pathogenesis of Reiter's syndrome (RS), but it is
      not known whether intact organisms are present in that tissue in any stage of the
      disease. The present study was undertaken to begin to address this question.
      METHODS: We used a highly specific and sensitive molecular hybridization
      screening system which detects chlamydial RNA, to examine synovial biopsy samples
      from 22 patients with various arthropathies, including 9 with RS. RESULTS: Seven
      of the 9 RS patients were positive for chlamydial RNA, while 3 of the 13 non-RS
      patients were also positive; positive results in the non-RS patients probably
      indicate the actual presence of the organism, since these patients had arthritis
      that was otherwise incompletely explained. CONCLUSION: The detection of
      chlamydial RNA, in combination with previous findings of chlamydia-like particles
      and/or chlamydial antigens in the synovium of RS patients, suggests that whole
      bacterial cells are present in that tissue.

PMID- 1374249
TI  - Identification of the epitope of a monoclonal antibody which binds to several
      cytochromes P450 in the CYP1A subfamily.
AB  - The monoclonal antibody, 3/4/2, which was raised against purified rat cytochrome
      P450 isoenzyme 1A1 (CYP1A1) binds to cytochromes P4501A in many species. It was
      shown by immunoblotting that the antibody binds to CYP1A1 in microsomal fractions
      prepared from rat, mouse, rabbit, hamster and human. The antibody also binds to
      cytochrome P450 isoenzyme 1A2 in microsomal fractions prepared from rabbit and
      human, but not rat or mouse. Using purified isoenzymes in an enzyme-linked
      immunosorbent assay it was found that the affinity of binding to the two rabbit
      hydrocarbon-inducible isoenzymes is reduced compared with that for rat CYP1A1.
      Binding is not affected by denaturation of the antigens. The effects of chemical
      and enzymatic treatments on rat CYP1A1 showed that the epitope contains a trypsin
      sensitive site that includes arginine, but lacks lysine. The epitope does not
      contain methionine, cysteine, aspartic acid or glutamic acid residues. In
      addition, digestion of the protein with cyanogen bromide produces a fragment of
      Mr 20,000 which contains the antibody binding site. By comparing the cross
      reactivity of the antibody with the primary structures of CYP1A1 and 1A2 from the
      rat, mouse, rabbit and human, and by considering the results of the chemical and
      enzymatic treatments, it was possible to deduce the likely location and structure
      of the binding site of 3/4/2 on members of the CYP1A subfamily. It is concluded
      that the epitope for this antibody is Phe-Arg-His-Ser-Ser-Phe, which lies at
      positions 380-385 in rat CYP1A1. Further, it is predicted from a model of the
      tertiary structure of eukaryotic cytochrome P450 that a part of this binding site
      lies within a helix in the native protein.

PMID- 1374251
TI  - Amelioration of antigen-induced arthritis in rabbits treated with monoclonal
      antibodies to leukocyte adhesion molecules.
AB  - OBJECTIVE: To examine the effects of treatment of antigen-induced arthritis in
      rabbits with a monoclonal antibody against CD18, the common beta chain of the
      leukocyte adhesion molecules. Intraarticular injection of antigen into primed
      rabbits elicits an acute inflammatory response followed by chronic arthritis in
      this model. METHODS: Anti-CD18 was given at the time of intraarticular antigen
      administration, and effects on the acute and chronic arthritis were investigated.
      Twenty-four rabbits were examined (11 controls, 3 receiving normal mouse IgG, and
      10 receiving anti-CD18). RESULTS: Flow cytometry of blood leukocytes at anti-CD18
      administration showed saturating amounts of mouse Ig coating all the circulating
      cells. Treatment effects on the acute arthritis (measured by quantitating the
      synovial cell exudate 24 hours after arthritis induction) were a profound
      reduction in the number of inflammatory cells and a striking decrease in the
      proportion of polymorphonuclear leukocytes recovered from the synovial cavity,
      indicating a decrease in acute inflammation. Treatment effects on the chronic
      synovitis (2 and 4 weeks later) compared with controls showed a significant
      decrease in synovial fluid cell counts at 2 weeks (1.7 versus 21.0 x 10(6)/joint,
      P less than 0.03) and at 4 weeks (7.4 versus 22.6 x 10(6)/joint, P less than
      0.05). Histologic evaluation of the synovium (0-3+ scale, scored "blindly") of
      anti-CD18-treated rabbits and controls showed marked decreases in subsynovial
      cell infiltration and lymphoid follicle formation both at 2 weeks (1.0 versus
      2.25, P less than 0.005; and 0 versus 1.75, P less than 0.001) and at 4 weeks
      (1.48 versus 2.17, P less than 0.01; and 0.75 versus 2.08, P less than 0.02).
      Quantitation of cartilage-bound immune complexes, and of synovial synthesis of Ig
      and specific antibody showed no differences between groups. CONCLUSION: These
      findings indicate that treatment with monoclonal antibody to CD18 not only
      modifies the initial acute arthritis, but also results in significant
      amelioration of the subsequent chronic inflammation in this animal model of
      rheumatoid arthritis.

PMID- 1374252
TI  - Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis
      syndrome and rheumatoid arthritis.
AB  - OBJECTIVE: To compare the levels of biogenic amines in the cerebrospinal fluid
      (CSF) of primary fibromyalgia syndrome (PFS) patients with those in the CSF of
      controls. METHODS: Metabolites of serotonin, norepinephrine, and dopamine were
      identified in CSF, using high performance liquid chromatography with coulometric
      detection. RESULTS: CSF levels of metabolites from all 3 neurotransmitters were
      lower in PFS patients than in controls. CONCLUSION: A low rate of turnover of
      several neurotransmitters supports the proposed hypothesis of a metabolic defect
      in PFS and suggests that the defect occurs at a neuroregulatory level.

PMID- 1374253
TI  - Project ROSES.

PMID- 1374254
TI  - Indomethacin for the treatment of symptomatic leiomyoma uteri during pregnancy.
AB  - Pain secondary to carneous degeneration is the most common complication of
      leiomyoma uteri during pregnancy. Conventional therapy utilizing bed rest and
      parenteral narcotic analgesics may often be ineffective. We retrospectively
      reviewed seven cases of degenerating fibroids complicating pregnancy where the
      prostaglandin synthetase inhibitor, indomethacin (25 mg orally every 6 hours),
      was used to treat symptoms of pain. In all cases, relief of symptoms was achieved
      within 48 hours of initiation of therapy. Two patients required a second course
      of therapy, and one patient required a third course. Mean duration of therapy was
      12 days. One fetus developed transient constriction of the ductus arteriosus and
      transient oligohydramnios. Two pregnancies aborted, one at 22.9 and one at 22.3
      weeks; however, no perinatal complications were directly attributable to
      indomethacin. The five term deliveries were of healthy normal infants. These
      retrospective data suggest that indomethacin may be effective in the treatment of
      pain associated with degenerating uterine leiomyomas in pregnancy.

PMID- 1374255
TI  - [Therapy of sensorineural hearing loss in the aged with arteriosclerotic disease:
      a comparison of hydroxyethyl starch and prostaglandin].
AB  - We assessed 42 patients (aged between 51 and 86 years, average age: 71.6 years)
      with chronic bilateral sensorineural hearing loss in old-age, who showed
      bilateral pathological loss of discrimination. This was a group of patients
      diagnosed with internal-angiological arteriosclerotic vascular disease (uni- or
      bilateral obliteration of the carotid artery, condition following a cerebral
      ischaemic attack or peripheral arterial occlusive disease). 21 patients received
      infusion treatment with hydroxyethylamylum (HAES-steril 10%), a further 21
      patients were infused with prostaglandin (Prostavasin, PGE-1) for three weeks.
      Pure tone audiometric and speech audiometric assessments were carried out before
      and after the infusion treatment (minimal loss of discrimination, overall word
      discrimination). It was statistically shown that there was no significant
      improvement of the average auditory threshold between 0.5 and 8 kHz using
      hydroxyethylamylum and prostaglandin. However, the examination results verify an
      increase of the minimal loss of discrimination and an improvement of speech
      comprehension following therapy with hydroxyethylamylum and prostaglandin.
      Between these two substances no difference was to be proved statistically. Our
      therapeutic results can be explained by the following considerations: 1. An
      improved circulation of the inner ear and the auditory pathway is to be regarded
      as possible reason for the achievement of the therapeutic effect. 2. An influence
      on the transmitter system of the cochlea and the auditory pathway is conceivable.

PMID- 1374256
TI  - [Is there a time limit for the treatment of sudden hearing loss?].
AB  - Improvement of hearing after-acute hearing loss, is more possible during the
      first days after its onset and the explanation remains unclear. When recovery of
      hearing happens many weeks later, this could be considered as a rare situation.
      During the last 8 years, we had 11 cases in which there was recovery of hearing
      within 4-26 weeks. In one case hearing recovery happened spontaneously and in the
      other cases after the application of a therapy schedule. In this paper, we
      present the audiological findings and we discuss the possible pathogenetic
      mechanism of this entity. Additionally, we stress the significance of that
      knowledge, in cases of medicolegal problems.

PMID- 1374257
TI  - [Determinants of lead concentration in the umbilical cord blood of 9189 newborns
      of a birth cohort in the government district of Braunschweig].
AB  - From September 1985 until August 1986 the possibility of lead concentration
      determination in umbilical cord blood was offered to all neonates in the district
      of Braunschweig by the Ministry of Social Affairs of Lower Saxony. A geometric
      mean concentration of 3.76 +/- 1.69 micrograms Pb/dl was found in 9189 neonates,
      being 64% of the total birth cohort. The median concentration was 3.59
      micrograms/dl. 4.7% of the children showed concentrations of above 10
      micrograms/dl. Lead concentrations of twins showed a strong linear correlation (r
      = + 0.94). They were higher than those of singleton births (p = 0.02). Lead
      concentrations in neonates were significantly associated with the age of the
      mother and with the birthweight of the newborn. Seasonal differentials were
      significant with higher values in summer (4.39 +/- 1.8 micrograms Pb/dl) compared
      to winter (3.25 +/- 1.5 micrograms/dl). Duration of daily participation in road
      traffic was independent of blood lead concentrations. Potential occupational lead
      exposure of a member of the household was also no significant risk factor for
      higher lead concentration in the newborn. Family homes constructed before 1955
      and those with lead water pipes were associated with significant increases of
      lead concentrations in neonates. Neighborhood was also significantly associated,
      with higher values in those living by main roads. In the southern part of the
      district lead concentrations were about 10% higher than in the northern part.
      Concentrations in neonates coming from cities were the same as in those coming
      from rural areas. Newborns from old lead mining and processing areas in the Harz
      mountains, in particular those coming from Oker-Harlingerode, had low lead
      concentrations in umbilical cord blood.

PMID- 1374258
TI  - Carrier sequence selection--one key to successful vaccines.
AB  - The trend towards epitopic vaccines has brought with it the problem of ensuring
      carrier function, a role previously filled by carrier sequences of the attenuated
      organism. Here, Howard Etlinger proposes the use of carrier epitopes, derived
      from vaccines already in use and selected for their ability to activate only
      helper T-cell responses, in the administration of B-cell-specific epitopic
      vaccines.

PMID- 1374259
TI  - Sequence similarity between NKSF and the IL-6/G-CSF family.

PMID- 1374260
TI  - Serotonin-norepinephrine interactions: a voltammetric study on the effect of
      serotonin receptor stimulation followed in the N. raphe dorsalis and the Locus
      coeruleus of the rat.
AB  - In vivo voltammetry with carbon fibre electrodes was used to study the effect of
      the serotoninergic (5-HT) neuronal system on the noradrenergic (NE) system in the
      Locus coeruleus of the rat. The voltammetric DOPAC signal in the Locus coeruleus,
      used as a measure of NE neuronal activity, was increased after systemic
      application of the 5-HT1B agonist CGS-12066B, the 5-HT2 antagonist ritanserin,
      and, to a lesser extent, by ipsapirone, a 5-HT1A agonist. The findings suggest
      that the NE neuronal system of the Locus coeruleus is stimulated by 5-HT1A and 5
      HT1B receptor activation and inhibited by 5-HT2 receptors. Likewise the 5-HT
      releaser and uptake inhibitor fenfluramine increased the DOPAC level in the Locus
      coeruleus. In contrast to the 5-HT1 agonists, which reduced 5-hydroxyindoleacetic
      acid (5-HIAA) in the Nucleus raphe dorsalis, ritanserin increased the 5-HIAA
      signal in this nucleus. This finding could help to explain the action of
      ritanserin as sleep-modulating substance.

PMID- 1374261
TI  - Bioactive peptides from 'alphabet soup'.

PMID- 1374262
TI  - Human therapeutics based on triple helix technology.
AB  - The application of triple helix technology to rational drug discovery is rapidly
      leading to the development of a new class of drugs, initially applicable for the
      effective and specific treatment of viral infections and, eventually, perhaps,
      cancer and immunological disorders. Issues such as stability, delivery,
      specificity, in vitro efficacy and acute toxicity, and the cost of synthesis are
      already being addressed: preliminary studies are yielding promising results.
      Further chemical modification of the oligonucleotides will probably be necessary
      to enhance affinity and efficacy, and comprehensive studies on the
      pharmacokinetics, toxicity, mutagenicity and in vivo efficacy of these compounds
      are still required. These, as well as scale-up synthesis and pharmaceutical
      formulation issues, are the focus of the R&D programs of a number of
      pharmaceutical laboratories.

PMID- 1374263
TI  - Ribozymes: stop making sense.

PMID- 1374264
TI  - Topical application of dithranol on normal skin induces epidermal
      hyperproliferation and increased Ks8.12 binding.
AB  - Although dithranol has been used for 75 years in the treatment of psoriasis, its
      working mechanism is still not resolved. In order to further define the mode of
      action of dithranol, the interference with normal skin was studied. The effect of
      dithranol on epidermal proliferation, keratinization and inflammation was
      examined using immunohistochemistry. Punch biopsies from 6 volunteers who applied
      dithranol 0.5% in petrolatum were taken before application, after 48 and 96 h.
      Biopsies were processed for assessing epidermal proliferation by Ki67 binding
      (cycling cells), for keratinization by Ks8.12 binding (keratin 13 and 16, keratin
      16 is expressed by hyperproliferative keratinocytes) and RKSE60 binding (keratin
      10). For assessing inflammation the antibodies antielastase (polymorphonuclear
      leukocytes (PMN)), T11 (T lymphocytes, CD2), T6 (Langerhans cells, CD1a) and WT14
      (monocytes/macrophages, CD14) were used. Ki-67 staining started to increase
      between 48 and 96 h whereas Ks8.12 binding had increased already between 0 and 48
      h. RKSE60 staining showed a decline between 48 and 96 h. Inflammation in the
      dermis showed an increase after 48 h, and continued to increase. In the
      inflammatory infiltrate, the accumulation of PMN was limited compared to the
      pronounced infiltration of T lymphocytes. Langerhans cell shape and epidermal
      position altered in 4 volunteers. Application of dithranol on normal skin
      produces analogies and discrepancies compared to application of dithranol on
      psoriatic lesions. Direct interference with epidermal growth and differentiation
      seems less likely as the antipsoriatic principle.

PMID- 1374265
TI  - The production and characterization of anti-Naegleria fowleri monoclonal
      antibodies.
AB  - Naegleria fowleri, a free-living amoeba commonly found in moist soil and fresh
      water, enters the body via the nasal mucosa and migrates along the olfactory
      nerve to the brain, where it causes acute amoebic meningoencephalitis. In the
      present study 7 clones secreting monoclonal antibodies (McAbs) against N. fowleri
      were produced and the effector function of them was investigated. Their isotypes
      were IgG1 (Nf 1, Nf 154), IgG3 (Nf 137) and IgA (Nf 1, Nf 2, Nf 256, Nf 279).
      Five McAbs (McAb Nf 2, Nf 279, Nf 27, Nf 154, Nf 137) were specific for N.
      fowleri by ELISA and recognized the antigenic determinants located on the
      trophozoite surface by IFAT and immunoperoxidase stain. These five McAbs had
      capacity to agglutinate N. fowleri trophozoites and inhibited the growth of the
      amoeba in culture medium. McAb Nf 2 inhibited proliferation of trophozoites in
      vitro significantly. Also the cytotoxicity of N. fowleri against CHO cell was
      reduced in the presence of McAb Nf 2 and McAb Nf 154. From these results McAb Nf
      2 was confirmed to weaken the virulence of the amoeba among 7 screened McAbs.

PMID- 1374266
TI  - Decreasing use of donated blood and reduction of bleeding after orthotopic heart
      transplantation by use of aprotinin.
AB  - Twenty patients undergoing orthotopic heart transplantation were randomized
      preoperatively to receive either the serine proteinase inhibitor aprotinin in a
      low dose (560 mg; n = 10) or a placebo (control group, n = 10) at the time of
      transplantation. Blood loss 24 and 48 hours after transplantation was
      significantly lower in the group treated with aprotinin (i.e., 510 ml vs 820 ml,
      p less than 0.01, and 690 ml vs 1000 ml, p less than 0.03, respectively.
      Accordingly, the aprotinin group required significantly less transfused blood in
      the first 48 postoperative hours 0 to 250 ml versus 0 to 1000 ml (p less than
      0.04). Seventy percent of the patients treated with aprotinin underwent
      transplantation without the need of nonautologous blood, compared with only 30%
      in the control group.

PMID- 1374267
TI  - Sterol carrier protein 2 (non-specific lipid transfer protein) is localized in
      membranous fractions of Leydig cells and Sertoli cells but not in germ cells.
AB  - The cellular and subcellular distribution of sterol carrier protein 2 (SCP2; nsL
      TP) was reinvestigated in rat testicular cells by Western blotting and
      immunocytochemistry, using the affinity purified antibody against rat liver SCP2.
      Western blot analysis revealed high levels of the protein in the somatic cells of
      the testis, e.g., Leydig and Sertoli cells whereas it could not be detected in
      germ cells. This cellular localization of SCP2 was confirmed by Northern
      blotting. Immunocytochemical techniques revealed that in Leydig cells,
      immunoreactive proteins were concentrated in peroxisomes. Although SCP2 was also
      detected in Sertoli cells, a specific subcellular localization could not be
      shown. SCP2 was absent from germ cells. Analysis of subcellular fractions of
      Leydig cells showed that SCP2 is membrane bound without detectable amounts in the
      cytosolic fraction. These results are at variance with data published previously
      which suggested that in Leydig cells a substantial amount of SCP2 was present in
      the cytosol and that the distribution between membranes and cytosol was regulated
      by luteinizing hormone. The present data raise the question in what way SCP2 is
      involved in cholesterol transport between membranes in steroidogenic cells but
      also in non-steroidogenic cells.

PMID- 1374268
TI  - Electrophoretic analysis of isoforms of glyoxalase II in clinical blood samples.
AB  - A non-denaturing polyacrylamide gel electrophoresis procedure is described for
      the analysis of isoforms of human red blood cell glyoxalase II (EC 3.1.2.6). A
      cathodic, continuous buffer electrophoresis system was developed, using a 60 g/l
      polyacrylamide gel with 25 g/l N,N1-methylene-bis-acrylamide in 50 mmol/l sodium
      succinate buffer, pH 5.5 and 1 degrees C. Staining for glyoxalase II activity
      involved (a) washing the gel with 50 mmol/l Tris-HCl buffer, pH 7.4 and 37
      degrees C, and (b) incubation with developing agent (0.5 g/l 3-[4,5
      dimethylthiazol-2-yl]- 2,5-diphenyltetrazolium bromide, 0.1 g/l 2,6
      dichlorophenolindophenol, 1 mmol/l S-D-lactoylglutathione in 100 mmol/l Tris-HCl,
      pH 7.4). Two activity bands were found in all human blood samples studied to
      date, probably reflecting the presence of two major isoforms. Optimal sample
      storage and preparation procedures and validation studies are described. This
      method is currently in use in an ongoing investigation of glyoxalase II isoforms
      in disease processes.

PMID- 1374269
TI  - Changes in actin state and chemotactic peptide receptor expression in
      granulocytes during cytokine administration after autologous bone marrow
      transplantation.
AB  - We studied the changes in actin state and chemotactic peptide receptor expression
      in granulocytes from patients receiving different cytokines following high dose
      chemotherapy and autologous bone marrow transplantation (ABMT). The F-actin
      content in granulocytes was higher in all patients following ABMT. However, in
      patients receiving granulocyte colony-stimulating factor (G-CSF) and macrophage
      colony-stimulating factor (M-CSF) the increase in F-actin content was much
      greater than in those not receiving these cytokines (159, 149, and 90% for G-CSF,
      M-CSF, and noncytokine group, respectively). Patients receiving granulocyte
      macrophage colony-stimulating factor (GM-CSF) had only a 62% increase in the F
      actin content, which was not statistically significant from patients undergoing
      ABMT without any cytokines. Although the basal level of F-actin was high
      following ABMT, granulocytes from all patients showed an additional increase in F
      actin content after stimulation with either the chemotactic peptide N-formyl
      methionyl-leucyl-phenylalanine (FMLP) or phorbol myristate acetate (PMA). The
      chemotactic peptide receptor expression was significantly higher in patients
      treated with ABMT alone or ABMT plus G-CSF. These observations suggest that the
      granulocytes generated following ABMT and cytokine administration may have
      different functional potential depending on the cytokine administered. Further
      studies to evaluate these potential differences are essential to devise optimal
      therapeutic protocols for maximizing the granulocyte protective function in this
      clinical setting.

PMID- 1374271
TI  - [Fatal cerebral hemorrhage caused by overdose of dicumarol, report of a case].

PMID- 1374270
TI  - Localization of transforming growth factor-beta at the human fetal-maternal
      interface: role in trophoblast growth and differentiation.
AB  - We examined the localization of transforming growth factor (TGF)-beta in first
      trimester and term human decidua and chorionic villi and explored the role of
      this factor on the proliferation and differentiation of cultured trophoblast
      cells. Two antibodies, 1D11.16.8, a mouse monoclonal neutralizing antibody
      capable of recognizing both TGF-beta 1 and TGF-beta 2 and CL-B1/29, a rabbit
      polyclonal antibody capable of recognizing TGF-beta 2, were used to
      immunolocalize TGF-beta in fixed, paraffin-embedded, or fixed, frozen sections of
      placenta and decidua, providing similar results. Intense labeling was observed in
      the extracellular matrix (ECM) of the first-trimester decidua and cytoplasm of
      term decidual cells. Syncytiotrophoblast cell cytoplasm as well as the ECM in the
      core of the chorionic villi of both first-trimester and term placentas exhibited
      a moderate degree of labeling. Strong cytoplasmic labeling was observed in the
      cytotrophoblastic shell of the term placenta. To examine the role of TGF-beta on
      trophoblast proliferation and differentiation, early passage cultures of first
      trimester and primary cultures of term trophoblast cells were established and
      characterized on the basis of numerous immunocytochemical and functional markers.
      These cells expressed cytokeratin, placental alkaline phosphatase, urokinase-type
      plasminogen activator, and pregnancy-specific beta glycoprotein, but not factor
      VIII or 63D3; they also produced hCG and collagenase type IV. Exposure of first
      trimester trophoblast cultures to TGF-beta 1 significantly inhibited
      proliferation in a dose-dependent manner. An antiproliferative effect was also
      noted in the presence of TGF-beta 2. These effects were abrogated in the presence
      of the neutralizing anti-TGF-beta antibody (1D11.16.8) in a concentration
      dependent manner. In a 3-day culture, exogenous TGF-beta 1 stimulated formation
      of multinucleated cells by the first trimester as well as term trophoblast cells.
      Addition of neutralizing anti-TGF-beta antibody to first-trimester trophoblast
      cells stimulated proliferation beyond control levels in a 24-h culture and
      reduced formation of multinucleated cells in a 3-day culture, indicating the
      presence of endogenous TGF-beta activity. These results indicate that TGF-beta
      produced at the human fetal-maternal interface plays a major regulatory role in
      the proliferation and differentiation of the trophoblast.

PMID- 1374272
TI  - Characterization of human monoclonal antibodies directed against hepatitis B
      surface antigen.
AB  - Four hybridoma cell lines stably secreting human monoclonal antibodies directed
      against hepatitis B surface antigen have been isolated. The monoclonal antibodies
      have been characterized by determining several allotypes, measuring affinity for
      HBsAg, binding to two HBsAg subtypes, and kinetics of antibody binding to solid
      adsorbed antigen. In addition, the relative position of the epitopes have been
      determined by competition in binding to HBsAg. The results indicate that human
      anti-HBsAg monoclonal antibodies of quite different properties can be isolated.
      Pharmacokinetics of one antibody have been measured in two rhesus monkeys. This
      monoclonal antibody, OST 577, has been compared to hyperimmune gamma globulins in
      a Bureau of Biologics approved radioimmunoassay. It is expected that these
      antibodies will be useful in preventing and treating hepatitis B.

PMID- 1374273
TI  - Anti-histone autoantibodies recognize centromeric heterochromatin in metaphase
      chromosomes and hidden epitopes in interphase cells.
AB  - IgM autoantibodies from a subset of patients with undifferentiated rheumatic
      disease syndromes stained mouse kidney nuclei with a distinctive variable large
      speckled (VLS) indirect immunofluorescence (IIF) pattern. However, these
      antibodies did not stain nuclei of tissue culture cells prepared with
      conventional fixation. These sera were shown to react with histone H3 by an
      enzyme-linked immunosorbent assay (ELISA), and adsorption with H3 reduced or
      eliminated the IIF reaction. Sera yielding a VLS-IIF pattern reacted in ELISA
      with all three H3 variants as well as the native (H3-H4)2 tetramer, but the
      reactive determinants were unavailable for binding when chromatin was the
      substrate. By IIF assay, the epitopes were exposed after treatment of tissue
      culture cells with 0.5 M NaCl, and were removed by 1.5 M NaCl. These sera also
      stained the centromeric region of metaphase chromosomes. These observations
      suggest that the VLS-IIF pattern is due to antibodies that recognize epitopes on
      constitutive heterochromatin near the centromere. The epitopes are exposed in
      differentiated cells but hidden in dividing cells. Histone in heterochromatin, or
      CENP-A, a histone-like protein in the centromere with a sequence similarity to
      histone H3, are candidates for the target antigen.

PMID- 1374274
TI  - Developing outcome standards for quality assurance activities.
AB  - When quality assurance programmes began to develop actively, 20 or so years ago,
      information connecting outcome and process was very scanty. However, with the
      development of the field of health care technology assessment, there is now much
      information on efficacy that has not been applied in the field to improve
      quality. At the same time, patient's satisfaction with care is coming to be seen
      as a valid measure of outcome of care. On the other hand, process measures of
      quality developed by practitioners working with a particular problem are often of
      doubtful validity, and could even be harmful. Increasingly, quality assurance
      programmes will be based on outcomes of care, or on process measures that have
      been linked clearly to outcome. Informatics can contribute to quality assurance
      in two ways. One is in the development of information on efficacy and safety of
      care through data banks, such as those reporting hospital death rates or
      insurance claims data. The other is to monitor outcomes of care directly. Up
      until now, technology assessment and quality assurance have developed as largely
      independent activities. A constructive approach to developing systems of quality
      assurance would be to incorporate technology assessment as part of the
      development of guidelines for quality assurance programmes.

PMID- 1374275
TI  - Lipase latex test for acute abdominal pain: comparison with serum lipase,
      trypsin, elastase and amylase.
AB  - The diagnostic capacity of a semiquantitative latex test for lipase measurement
      was compared with the measurement of other pancreatic enzymes in 100 consecutive
      patients admitted to a general hospital for recent onset of severe abdominal
      pain. Positive results of the test were found in two patients with acute
      pancreatitis, and in one out of three chronic pancreatitis relapses. The test
      yielded false-positive results only in two patients who had no apparent
      pancreatic involvement. A marginal increase in other pancreatic enzymes was found
      in a few patients with acute biliary or appendicular problems. In conclusion, the
      lipase latex test can be suggested in an emergency setting as a quick and
      reliable alternative to serum amylase to rule out a diagnosis of acute
      pancreatitis.

PMID- 1374276
TI  - Diagnosis of hepatocellular carcinoma by fine needle biopsy of portal vein
      thrombosis.
AB  - The authors describe a case of HBsAg positive liver cirrhosis and elevated alpha
      fetoprotein value (AFP) where imaging techniques failed to detect focal liver
      changes. Diagnosis of hepatocellular carcinoma was reached by ultrasound-guided
      fine needle aspiration biopsy of portal vein thrombosis.

PMID- 1374277
TI  - Structural differences in the outer core region of lipopolysaccharides derived
      from members of the genus Salmonella.
AB  - Spontaneous and P22-resistant rough mutants, respectively, selected from
      Salmonella IV (18: z36, z38:-) and S. djakarta (48: z4, z24:-), appeared to lack
      the epitope recognized by the T6 monoclonal antibody which had been previously
      shown to correspond to the terminal alpha-1,2-linked N-acetyl-D-glucosamine
      residue of the Salmonella lipopolysaccharide (LPS) Ra core. LPSs and core
      oligosaccharides were therefore prepared from these two rough mutants and
      analysed by chemical and serological methods. Sugar analyses as well as
      methylation and 13C-NMR studies indicated that rough mutants derived from these
      two serotypes indeed possessed outer core structures differing from those of the
      well-characterized Salmonella Ra core. Serological data corroborated the chemical
      findings. Proposed structures of the outer core regions of these two R-types are
      presented and the significance of the findings is discussed.

PMID- 1374278
TI  - Some morphological and histochemical features of the midgut myenteric plexus of
      the common European frog, Rana esculenta.
AB  - The neuron morphology and distribution of four putative transmitters were
      investigated in the myenteric plexus of frog (Rana esculenta) midgut. The gross
      morphology was revealed by NADH-diaphorase histochemistry, and the shape of the
      neurons by silver impregnation. Nerve cells had heterogeneous distribution: they
      either formed ganglia or placed as solitary neurons in the duodenum, while in the
      rest of the midgut only solitary neurons were observed. Three morphologically
      distinct cell types were revealed by silver impregnation: mainly type I and type
      II neurons cells were seen in the duodenum, while the rest of the intestine
      contained type II and III cells. Catecholamine fluorescence was revealed in nerve
      fibres in the duodenum, while few small nerve cells were observed in the small
      intestinal region. Acetylcholinesterase histochemistry showed strongly reactive
      nerve cells that were associated with the main fibre bundles in the duodenum.
      Only longitudinally oriented fibres and occasionally stained neurons were seen in
      the small intestine. Substance P immunocytochemistry revealed an extensive
      plexus, which contained a moderate number of stained perikarya in the full length
      of the midgut. Gamma-aminobutyric acid showed non-uniform distribution in the two
      parts of the midgut: a stronger and more regular fibre staining was found in the
      duodenum then in the rest of the intestine. Ultrastructural observations
      demonstrated that intrinsic neurons received synaptic inputs from the profiles
      contained agranular vesicles, while "P"-type profiles established close contacts
      with neurons. Both profile types formed close contacts with the smooth muscle
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374279
TI  - Poor palliation of colorectal malignancy with the neodymium yttrium-aluminium
      garnet laser.
AB  - The neodymium yttrium-aluminium-garnet (NdYAG) laser was used to palliate the
      symptoms of 38 patients with rectal carcinoma unsuitable for radical surgery. All
      patients with small tumours (n = 6) reported resolution of their symptoms. In
      contrast, those with large tumours frequently showed little improvement (n = 18)
      and alternative surgical management was necessary in 12 patients. The overall
      early mortality rate (less than 1 month after first treatment) was 21 per cent.
      The NdYAG laser offers good palliation and may even cure small colorectal tumours
      in patients who are unsuitable for surgery. For large circumferential tumours,
      those associated with obstruction and those close to or involving the anal
      sphincters, however, the results are poor and better symptom control may be
      achieved by other means.

PMID- 1374280
TI  - Laparoscopy in the management of pancreatic cancer: endoscopic
      cholecystojejunostomy for advanced disease.
AB  - Following a period of animal experimentation in pigs, a laparoscopic technique
      for sutured gastrointestinal and bilioenteric anastomoses was developed and its
      safety and efficacy tested in chronic experiments. The method involves the
      construction of a preformed external jamming loop knot and continuous suturing
      using a specially developed Endoski needle. The technique was used to construct a
      cholecystojejunostomy in five patients with advanced cancer of the pancreas (four
      hand-sutured and one stapled/sutured). Four of the patients recovered from the
      procedure with no complications, minimal postoperative discomfort and complete
      relief of their jaundice. In one patient relief of jaundice was slow due to
      blockage of the anastomosis by debris and blood clot; this resolved following
      removal of the inspissated material. This minimally invasive procedure has the
      potential for complete palliation with short hospital stay and avoids the hazards
      of endoscopic stenting such as encrustation and cholangitis.

PMID- 1374281
TI  - Renal and adrenal sympathetic preganglionic neurons in rabbit spinal cord:
      tracing with herpes simplex virus.
AB  - We mapped sympathetic renal preganglionic neurons in the rabbit spinal cord using
      Herpes simplex virus retrograde transneuronal tracing after application of the
      virus to the renal nerve. Virus-positive neurons were found in the spinal cord
      from T7 to L2, principally in the ipsilateral intermediolateral cell column.
      Renal and adrenal preganglionic neurons are largely separate populations.
      Extensive nonspecific spread of virus from infected cells to neighboring neurons
      does not appear to occur.

PMID- 1374282
TI  - Early transient expression of somatostatin (SRIF) immunoreactivity in dorsal root
      ganglia during ontogenesis in the rat.
AB  - Immunofluorescence was used in the rat to study the early ontogenetic expression
      of somatostatin (SRIF) in the dorsal root ganglia (DRGs) from gestational day
      10.5 to day 15.5. SRIF-immunoreactivity (IR) was not detectable in day-10.5
      embryos, was first observed in DRGs at day 11.5, reached a peak in intensity and
      distribution at around day 13.5 and thereafter decreased to become undetectable
      by day 15.5 in the DRGs of the trunk region. The dynamic expression of SRIF-IR in
      DRG perikarya could be correlated with its expression in nerve fibers located in
      the limbs and the abdominal mesenchyme. Thus, SRIF-IR is expressed at a time when
      sensory fibers could have established connections with their embryonic targets
      and when DRG neurons could have undergone their final mitotic phase. These data
      showing the earliest and transient expression of a neuropeptide in developing
      DRGs confirm and extend the notion that SRIF plays an important role in
      developmental processes.

PMID- 1374283
TI  - Estrogen receptive neurons in the preoptic area of the rat are postsynaptic
      targets of a sexually dimorphic enkephalinergic fiber plexus.
AB  - The periventricular preoptic area (pePOA) is a sexually dimorphic component of
      the rat forebrain that contains a sexually dimorphic Met-enkephalin
      immunoreactive (ENK-ir) fiber plexus. This plexus is especially dense in the
      female while only scattered ENK-ir fibers are present in the pePOA of the male.
      Abundant estrogen receptive neurons are located in the pePOA of both the female
      and male. This experiment was conducted to determine if estrogen receptive
      neurons in the pePOA are postsynaptic targets of ENK-ir terminals. Double label
      ultrastructural localization of estrogen receptor (ER)-ir neurons and ENK-ir
      fibers was performed using the chromogens 3,3',5,5'-tetramethylbenzidine (TMB)
      and diaminobenzidine tetrahydrochloride (DAB), respectively. TMB-stained ER-ir
      neurons contained electron dense crystalline spicules located predominantly in
      their nuclei. Flocculent DAB reaction product was distributed over membraneous
      structures in ENK-ir fibers and terminals. Numerous ER-ir neurons were present in
      the pePOA of the male and female. In females, many ENK-ir terminals, both
      synaptic and non-synaptic, contacted the perikarya of ER-ir neurons. In contrast,
      many fewer ENK-ir terminals made contact on ER-ir neurons in the male. Thus,
      these results provide morphological evidence that ENK-ir neurons can regulate ER
      ir neurons in the pePOA. Moreover, because expression of the ENK-ir pePOA fiber
      plexus is estrogen-sensitive in the female, these results suggest strongly that
      estrogen may regulate these neurons both pre- and postsynaptically. Finally,
      these results provide additional evidence for the involvement of the sexually
      dimorphic pePOA ENK-ir fibers plexus in the control of estrogen-mediated function
      in the female.

PMID- 1374284
TI  - Cortical connections of the inferior arcuate sulcus cortex in the macaque brain.
AB  - Injections of the retrograde/anterograde tracers Wheat Germ Agglutinin
      Horseradish peroxidase (WGA-HRP) into the cortex along the banks of the inferior
      limb of the arcuate sulcus in the cortex of 4 macaque monkeys (Macaca
      fascicularis) were used to investigate its cortico-cortical connections. All
      injections produced transported label within the sulcus principalis, the ventral
      lateral prefrontal cortex, the anterior cingulate sulcus and the dorsal insular
      cortex. The distribution of label within each of these areas differed slightly
      depending on the injection site. Injections along the caudal bank of the inferior
      arcuate sulcus label premotor, supplementary motor, and precentral motor areas
      but produce relatively sparse prefrontal labeling. Posteriorly label is
      transported to the inferior parietal cortex and the dorsal opercular bank of the
      Sylvian fissure. Injections along the rostral bank of the sulcus do not label
      motor areas but produce labeling in dorsal, lateral and orbital prefrontal areas,
      and in cortex along the ventral bank of the superior branch of the arcuate
      sulcus. Posteriorly label is transported to cortical areas in the superior
      temporal gyrus including the dorsal bank of the superior temporal sulcus. The
      more dorsal rostral bank injection produced both superior temporal and some
      sparse inferior parietal labeling and the more ventral rostral bank injection
      produced extensive superior temporal labeling but no parietal labeling. No
      labeling was ever seen in cortex ventral to the fundus of the superior temporal
      sulcus. Although other auditory recipient prefrontal areas have been reported,
      this is the first demonstration of a region chiefly devoted to auditory
      connections within the ventral frontal cortex. Its adjacency to areas associated
      with vocal muscle movement, and its connections to midline cortical areas
      associated with vocal functions in both primates and humans may provide important
      clues to the organization of Broca's language area.

PMID- 1374285
TI  - Multiple ionic mechanisms are activated by the potent agonist quisqualate in
      cultured cerebellar Purkinje neurons.
AB  - Current clamp recordings were used to analyze responses of cultured cerebellar
      Purkinje neurons to quisqualate and several other selective non-N-methyl- D
      aspertate (NMDA) agonists. Quisqualate, a potent agonist in the cerebellar
      Purkinje neuron, evoked both short- and long-term changes in excitability, that
      activated within seconds and lasted for several minutes. Two components of the
      response were activated differentially by subtype selective agonists, and
      differed in their mechanism of expression and time course. The initial component
      of the response was activated by ionotropic agonists ((RS)-d-amino-3-hydroxyl-5
      methyl-4-isoxazolepropionic acid (AMPA) domoate), and by quisqualate and
      glutamate which are effective at both the ionotropic and metabotropic quisqualate
      receptor subtypes, but not by the metabotropic agonist trans (+/-)-1-amino-1,3
      cyclopentanedicarboxylic acid (ACPD). This component was dependent on
      extracellular Na+, and characterized by a rapid depolarization with a short
      latency (less than 1-2 s) and a decrease in membrane resistance as expected for
      an ionotropic reponse. The rapid depolarization extended into an agonist
      dependent plateau phase, which could not be evoked by depolarization alone. The
      second ('late') phase of the response was a slowly-activating, long-lasting
      change in membrane excitability, accompanied by little or no change in the
      membrane potential. The late phase, marked by an increase in voltage-dependent
      bursting spike activity, was induced by the metabotropic agonist, ACPD, and by
      quisqualate and glutamate, but not by ionotropic selective agonists such as AMPA.
      Little or no bursting was evoked by AMPA, domoate, kainate or homocysteate. This
      late phase was also accompanied by increases in the magnitude and duration of the
      complex spikes and in the afterhyperpolarization following brief current-driven
      depolarizations. The slower time course of the late component is consistent with
      a pathway involving second messenger systems. Our results support the hypothesis
      that coregulation of both ionotropic and metabotropic mechanisms produces the
      complex and prolonged excitatory response characteristic of the Purkinje neuron.

PMID- 1374286
TI  - [Investigation of anti-hepatitis C virus in the sera of different populations of
      Beijing].
AB  - A study of anti-HCV in the sera of different populations of Beijing was
      conducted. Of the general population, 2.1% (9/438) were anti-HCV positive, and of
      the patients that underwent blood transfusion 11.1% (6/54) were anti-HCV
      positive. Among patients with chronic liver diseases, anti-HCV was positive in
      10.5% (36/342) of patients with chronic persistent hepatitis (CPH), 12.1%
      (13/107) of those with chronic active hepatitis (CAH), 42.6% (63/148) of those
      with liver cirrhosis (LC) and 38.4% (20/52) of those with hepatocellular
      carcinoma (HCC). HBsAg and anti-HCV were both positive in none of the general
      population, in 6.7% (23/342) of patients with CPH, in 8.4% (9/107) of those with
      CAH, in 31.1% (46/148) of those with LC and in 28.9% (15/52) of those with HCC.
      In the development of hepatitis into chronicity, detection of anti-HCV is of
      great significance. It was found that HBV-HCV coinfection made the condition of
      the patients with hepatitis worsened and it had close relations with
      hepatocellular carcinoma. Investigation in subjects below the age of 35 in the
      general population and in patients with chronic hepatitis indicate that besides
      the mother-to-infant route or the route of blood transfusion, HCV has other
      routes of propagation.

PMID- 1374287
TI  - Peptide epitope binding and fluorescence quenching with the anti-mucin antibody
      C595.
AB  - The Fab fragment of the anti-polymorphic epithelial mucin antibody C595 (IgG3,
      kappa) has been produced by digestion with papain. The purified antibody fragment
      retained its binding activity for the mucin in an indirect radioisotopic
      antiglobulin assay. The binding constant of the Fab fragment for the synthetic
      peptide (PDTRPAPGSTAPPAHGVTSA) corresponding to the 20-amino acid tandem repeat
      sequence found in the mucin protein core was determined to be 0.3 x 10(6) M-1 by
      measuring the capacity of the peptide to quench the fluorescence of the Fab
      fragment.

PMID- 1374288
TI  - Phenotypic and functional characterization of cytotoxic cells derived from
      endomyocardial biopsies in human cardiac allografts.
AB  - This study was undertaken to characterize the phenotype and function of
      lymphocytes derived from endomyocardial biopsies in heart transplant patients. To
      this aim, tissue infiltrating lymphocytes were derived from seven heart
      transplant patients and were analyzed for the expression of a panel of markers,
      including CD3, CD4, CD8, CD16, CD56, CD45RA, CD45RO, alpha/beta and gamma/delta T
      cell receptor, and for their ability to lyse a series of targets, including NK
      sensitive K-562 targets, NK-resistant Raji targets, donor related, and unrelated
      normal splenocytes. Our data show that the majority of cultured lymphocytes
      expressed the CD3+ phenotype and the alpha/beta T cell receptor. The CD4 and CD8
      molecules were heterogeneously expressed among T cell lines tested. Concerning
      cytotoxic related markers, a significant percentage of cells were CD56+. The
      evaluation of CD45 isoforms showed that both "naive" and "memory" cells were
      present among heart TIL. Cytotoxic in vitro studies demonstrated that all our T
      cell lines showed an efficient cytotoxic machinery when tested against NK
      sensitive targets. A marked lysis of donor-related splenocytes was demonstrated
      in all patients tested. To investigate the role of CD3 and HLA class I molecules
      in the cytotoxic mechanisms taking place in human heart allograft rejection
      mechanisms, TIL were assessed for their lytic activity against different targets
      in the presence of anti-CD3 and anti-HLA class I monoclonal antibodies (mAbs).
      Although donor-specific cytotoxicity was considerably inhibited by the anti-CD3
      mAb, no inhibitory effect was displayed by this antibody on TIL-mediated
      cytotoxicity against donor-unrelated splenocytes. Anti-HLA class I mAb was able
      to inhibit both allospecific and nonallospecific cytotoxicity. These data suggest
      that different types of cytotoxic cells may be propagated from biopsy specimens
      of heart transplant patients.

PMID- 1374289
TI  - Effects of tolerance induction on early cell cycle progression by Th1 clones.
AB  - Human gamma-globulin (HGG)-specific mouse Th1 clones exposed to tolerogenic
      signals provided by HGG-pulsed paraformaldehyde-fixed splenocytes (HGG-FAPC) were
      analyzed for antigen-induced progression through the early phases of the cell
      cycle. Exposure of Th1 clones to HGG-FAPC in primary cultures inhibits the
      ability of the clones to synthesize DNA in response to HGG and normal APC in
      secondary cultures. The Th1 clones in these secondary cultures were found to be
      blocked in G1a phase as evidenced by cell cycle analysis and by reduced numbers
      of cells expressing high levels of IL-2R and TfR. This cell cycle blockade of Th1
      cells was not observed if the secondary cultures were stimulated with IL-2
      containing Con A CM instead of antigen. These data suggest that in our system the
      inhibition in antigen-induced cell cycle progression associated with Th1
      tolerance induction occurs at the G1a/G1b phase transition.

PMID- 1374290
TI  - Generation of phosphatidic acid and diacylglycerols following ligation of surface
      immunoglobulin in human B lymphocytes: potential role in PKC activation.
AB  - We have examined signal transduction via membrane IgM (mIgM) in resting and
      cycling human B cells. Crosslinking mIgM on all of the cell types studied
      transduced a signal through the phosphatidylinositol pathway, producing inositol
      1,4,5-trisphosphate and release of intracellular free calcium. These second
      messengers were formed regardless of quantitative or qualitative differences in
      the surface expression of mIgM: cells that had low levels of surface IgM (T-51)
      or had no light chain associated with surface heavy chain (DB) signaled
      phosphatidylinositol pathway activation after mIgM crosslinking. Production of
      specific lipid products in nonquiescent B cells differed from that in normal
      resting cells. Ligation of surface immunoglobulin on resting B cells resulted in
      sustained increases of both diacylglycerol and phosphatidic acid, two lipids that
      can influence PKC activation. Whereas PKC was strongly activated in normal
      tonsillar B cells, several cell lines had reduced PKC activation following
      crosslinking of mIgM. The reduction in protein kinase C activation correlated
      with the absence or reduced levels of phosphatidic acid or diacylglycerol
      following stimulation: protein kinase C translocated and was activated only in
      cells that had elevated levels of both diacylglycerides and phosphatidic acid.
      Anti-IgM-induced phosphorylation of a protein kinase C substrate protein CD20,
      also increased in those cells having PKC activation and not in cells in which
      kinase activity was reduced. CD20 phosphorylation also increased following the
      direct addition of exogenous phosphatidic acid to resting B cells. Together,
      these observations show that the generation of lipid products following mIgM
      crosslinking in resting cells can vary from that in cycling cells and may relate
      to the different levels of PKC activation. In a companion study we report that
      ligation of surface IgM activates both an acyltransferase and phospholipase D to
      form phosphatidic acid.

PMID- 1374292
TI  - Human lymphocytes lack substance P receptors.
AB  - Substance P (SP), a neuropeptide found in high concentrations in the gut, is
      reported to have many potent immunomodulatory actions. This study evaluated some
      effects of SP on human peripheral blood lymphocytes (PBL) and jejunal
      intraepithelial lymphocytes (IEL) and the expression of SP receptors on these and
      other lymphocytes types. In contrast to previous studies, SP (10(-8) or 10(-12)
      M) did not affect the proliferation (spontaneous or mitogen-induced) nor
      spontaneous cytotoxicity by PBL or IEL. To determine whether this
      unresponsiveness was due to an absence of SP receptors, the SP binding potential
      of these and other human lymphocyte types was determined by Scatchard analysis of
      radioligand binding. The IM-9 B lymphoblastoid cell line, used as a positive
      control, demonstrated 4838 +/- 603 or 3131 +/- 832 receptors per cell, with a Kd
      of 0.21 +/- 0.01 or 0.18 +/- 0.09 nM, using [3H]SP or 125I-SP, respectively. No
      receptors were found on PBL, polymorphonuclear leukocytes, splenocytes, IEL, or
      jejunal lamina propria lymphocytes using either radioligand. These findings
      dispute the presence of large numbers of SP receptors on lymphocytes in
      peripheral blood, spleen, or intestinal mucosa, and argue against any major
      effect of SP on T cell proliferation or spontaneous cytotoxicity.

PMID- 1374291
TI  - The response of human decidual leukocytes to IL-2.
AB  - The phenotype of human decidual leukocytes, composed predominantly of CD3-CD16(-)
      CD56bright cells, was examined after culture with IL-2 by immunofluorescence and
      flow cytometry. After IL-2 stimulation the phenotype became like that found on
      classical NK cells, with an increased proportion of cells expressing CD16. The IL
      2R alpha was absent before and after IL-2 stimulation. However, the intermediate
      affinity receptor, IL-2R beta, was expressed by CD56bright decidual cells, but
      this receptor was downregulated after IL-2 stimulation. IL-2-induced
      proliferation of CD56+ decidual cells could be blocked using TU27, a monoclonal
      antibody to the IL-2R beta. These findings indicate activation of decidual
      leukocytes by IL-2 occurs through the IL-2R beta alone.

PMID- 1374293
TI  - Analysis of TCR V beta gene usage and encephalitogenicity of myelin basic protein
      peptide p91-103 reactive T cell clones in SJL mice: lack of evidence for V gene
      hypothesis.
AB  - We have analyzed the epitope specificity and encephalitogenicity of peptides that
      span the C terminus of MBP, p84-103. Our studies show that multiple antigenic
      epitopes with disease-inducing capacity exist in SJL mice. Three peptides that
      span this region were examined and found to be immunogenic. However, the mode of
      immunization (active or passive) determined the incidence and severity of EAE. In
      our experiments adoptive transfer of p91-103-reactive T cell lines was most
      consistent in the development of disease. Interestingly, the response to peptides
      p89-101, p91-103, and p84-102 was absent following immunization with MBP. This
      suggests that although p91-103 and p89-101 were encephalitogenic they were not
      the major immunogenic epitopes following immunization with MBP. Analysis of a
      panel of eight p91-103-reactive T cell clones showed significant heterogeneity in
      the fine specificity, the TCR V beta gene usage, and in their ability of transfer
      EAE. These studies suggest that in SJL mice the epitopes involved in the
      pathogenesis of disease are multiple and there is no clear correlation between
      encephalitogenicity and TCR V beta gene usage. These observations argue against
      the presence of a dominant TCR V beta gene in the pathogenesis of EAE in SJL
      mice.

PMID- 1374294
TI  - Chemical modification of fumagillin. I. 6-O-acyl, 6-O-sulfonyl, 6-O-alkyl, and 6
      O-(N-substituted-carbamoyl)fumagillols.
AB  - The hydroxy group of fumagillol (3), a degradation product of fumagillin (1), was
      acylated, sulfonylated, alkylated or carbamoylated, and the anti-angiogenic
      activity of the resulting products was examined. These compounds inhibited the
      angiogenesis induced by basic fibroblast growth factor in the rat corneal
      micropocket assay and the growth of vascular endothelial cells in vitro. Among
      them, compound 2 (AGM-1470) was found to show the most potent inhibitory effect
      on the growth of vascular endothelial cells and was selected from this series as
      a candidate for further development.

PMID- 1374295
TI  - Inhibitory effects of endosulfan on gap junctional intercellular communication in
      WB-F344 rat liver cells and primary rat hepatocytes.
AB  - The chlorinated cyclodiene insecticide endosulfan is a potent inhibitor of gap
      junctional intercellular communication (GJIC) in vitro, a property shared by many
      tumour promoters and suggested to indicate an intrinsic tumour-promoting
      potential. However, endosulfan did not act as a tumour promoter in an altered
      hepatic foci assay in the rat in vivo, and ambiguous results regarding the
      carcinogenic potential of endosulfan have emerged from long-term studies in
      rodents. In the present study the GJIC-inhibitory potentials of the two isomers
      of endosulfan were investigated in WB-F344 rat liver epithelial cells and primary
      rat hepatocytes. The results show that both isomers are inhibitors of GJIC.
      However, beta-endosulfan (ENDO beta) is a more potent inhibitor of GJIC in
      primary rat hepatocytes than alpha-endosulfan (ENDO alpha), whereas the two
      isomers were equally potent as inhibitors of GJIC in WB-F344 rat liver cells. In
      primary rat hepatocytes membrane-permeant dibutyryl cyclic AMP (dB-cAMP)
      counteracts the inhibitory effect of ENDO beta without affecting the effect of
      ENDO alpha. However, in WB-F344 rat liver cells dB-cAMP failed to prevent the
      inhibitory effects of either ENDO alpha or ENDO beta. In addition, studies in WB
      F344 rat liver cells show that ENDO alpha beta does not decrease the
      intracellular cAMP concentration. Thus, it is unlikely that ENDO alpha beta or
      its isomers and metabolites inhibit GJIC by lowering the intracellular cAMP
      concentration. Furthermore, comparison of the effective doses and recovery times
      imply that GJIC in WB-F344 rat liver cells is more sensitive to treatment by ENDO
      alpha beta, its isomers and metabolites than GJIC in primary rat hepatocytes.
      Thus, the present results demonstrate significant differences between primary rat
      hepatocytes and WB-F344 rat liver cells in the response of their GJIC to
      endosulfan.

PMID- 1374296
TI  - Initiation by bleomycin of hepatocellular foci in the rat.
AB  - The antitumor antibiotic, bleomycin, was tested for activity as an initiator of
      hepatocellular foci and neoplasms in rats. The compound was administered in a
      single dose via the portal vein 4 h after the proliferative stimulus of a two
      thirds partial hepatectomy. Rats were subsequently fed diet containing
      phenobarbital for up to 41 weeks to promote the development of initiated
      hepatocytes. Bleomycin-treated livers displayed significantly increased
      frequencies of basophilic hepatocellular foci and hepatocellular foci which
      retain glycogen during fasting. Foci that express glutathione-S-transferase
      (placental form) were not initiated by bleomycin. Hepatocellular neoplasms were
      infrequently seen in bleomycin-treated livers (5% incidence). The results suggest
      that oxygen radical-mediated DNA damage may initiate, within populations of
      proliferating hepatocytes, new lineages of altered hepatocytes that form foci but
      have low probability of progressing to neoplasms during promotion with
      phenobarbital.

PMID- 1374297
TI  - Identification of multi-drug resistant cells in sensitive Friend leukemia cells
      by quantitative videomicrofluorimetry.
AB  - The cellular resistance to cytotoxic drugs, particularly to anthracyclines,
      remains a major problem in cancer chemotherapy. A number of biochemical
      mechanisms have been described, one of them being a lower accumulation of drugs
      in resistant cells. The accumulation of Ho33342 in sensitive and resistant Friend
      leukemia cells was studied by quantitative fluorescence image analysis, a method
      which allows investigations to be made on living tissues and cells. The intensity
      of fluorescence is related to the amount of Ho33342 accumulated into the cells
      and has been found to be more intense in sensitive cells than in resistant ones.
      Moreover, the retention of this vital dye was inversely related to the degree of
      resistance in the three resistant cell lines. The addition of verapamil, which is
      known to reverse resistance to anthracyclines, resulted in an increase of the
      amount of Ho33342 accumulated in the resistant cells. Ho33342 presents a higher
      quantum yield than any other anthracyclines, such as adriamycin and can be used
      as a microfluorimetric probe to identify the resistant cells in a heterogeneous
      cell population.

PMID- 1374298
TI  - Heparin inhibits the expression of tissue-type plasminogen activator by smooth
      muscle cells in injured rat carotid artery.
AB  - Smooth muscle cells (SMCs) in balloon-injured rat carotid artery express tissue
      type plasminogen activator (t-PA) at a time when they are migrating from the
      media to the intima. Since heparin inhibits SMC migration and intimal thickening,
      we have examined the possibility that heparin might also inhibit t-PA expression.
      Heparin (nonanticoagulant fraction; molecular weight, approximately 6,000) was
      administered by continuous intravenous infusion (1.0 mg/kg per hour) to Sprague
      Dawley rats subjected to balloon injury of the left common carotid artery. At
      various times up to 14 days after injury, plasminogen activator expression was
      analyzed by zymography, plasmin generation, enzyme-linked immunosorbent assay,
      Northern blotting, and in situ hybridization. This dose of heparin inhibited SMC
      accumulation at 14 days by 60%. Both urokinase plasminogen activator (u-PA) and t
      PA activity increased in injured arteries and reached a maximum at 7 days.
      Heparin treatment decreased t-PA, but not u-PA, activity. Total t-PA protein was
      decreased by treatment with heparin but not chondroitin sulfate, and the decrease
      in t-PA protein was associated with decreased t-PA mRNA in the media. These
      results in the injured rat carotid artery agree with our earlier observations
      that heparin inhibits t-PA gene expression in cultured baboon aortic SMCs. They
      also provide support for the hypothesis that heparin interferes with the
      expression of certain proteases required for SMC migration and proliferation.

PMID- 1374299
TI  - Nitric oxide modulates coronary autoregulation in the guinea pig.
AB  - A guinea pig heart Langendorff preparation was used in the present study to test
      the hypothesis that the coronary endothelium modulates coronary autoregulation
      through the production of nitric oxide (NO). Pacing at 250 beats per minute and
      venting the left ventricle to ensure that the hearts did no external work were
      performed in an attempt to reduce the metabolic stimulus to coronary vasomotion
      and keep it constant. We measured the responses of coronary flow and oxygen
      metabolism to stepwise changes of the perfusion pressure over the range between
      18 and 85 mm Hg. The hearts exhibited autoregulation between 25 and 55 mm Hg and
      active vasodilation at perfusion pressures above that range. Perfusion with 100
      microM NG-nitro-L-arginine (NNLA), an inhibitor of NO synthase, decreased
      coronary flow over the entire range of perfusion pressures and abolished active
      vasodilation over 65 mm Hg, thus widening the autoregulatory range. The
      administration of 200 microM L-arginine, but not D-arginine, reversed the action
      of NNLA. Inhibition of the cyclooxygenase pathway by 10 microM indomethacin did
      not affect autoregulation. Perfusion with 1 nM arginine vasopressin, a direct
      smooth muscle constrictor, lowered coronary flow rate to the same extent as NNLA
      at 55 mm Hg but did not prevent the pressure-dependent increase in flow above
      that pressure. These observations suggest that 1) the coronary endothelium
      actively modulates coronary autoregulation through the production of NO but not
      prostanoids, 2) mechanical stress (shear stress and/or stretching secondary to
      vasodilation) may be the stimulus to NO production, especially above the
      autoregulatory range, and 3) autoregulatory tone is likely to be myogenic in
      origin rather than mediated by extrinsic vasoconstrictors.

PMID- 1374300
TI  - The determination of asialoglycoforms of serum glycoproteins by lectin blotting
      with Ricinus communis agglutinin.
AB  - Serum proteins were fractionated by polyacrylamide gel electrophoresis under
      denaturing conditions and transferred to nitrocellulose membranes. The blotted
      polypeptides were probed with biotinylated Ricinus communis lectin (RCA120)
      followed by streptavidin/alkaline phosphatase. This procedure detected five
      asialoglycoproteins (alpha 2-macroglobulin, transferrin, alpha 1-antitrypsin,
      alpha 1-antichymotrypsin and haptoglobin beta chain). The asialoform of the alpha
      1-trypsin inhibitor was found to be decreased in inflammation.

PMID- 1374301
TI  - Effects of xylitol- and/or glutamine-supplemented parenteral nutrition on septic
      rats.
AB  - 1. The effects of parenteral nutrition with or without xylitol and/or glutamine
      supplementation were studied in septic rats after 4 days of treatment. 2. Septic
      rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition
      survived sepsis significantly better than other parenteral nutrition-treated
      septic rats: the cumulative percentage of deaths over 4 days in septic rats
      treated with xylitol-glutamine-supplemented parenteral nutrition was 9.5%
      compared with 54.5% in septic rats given parenteral nutrition without xylitol and
      glutamine, and 52.4% in septic rats treated with parenteral nutrition
      supplemented with glucose. 3. Xylitol- and/or glutamine-supplemented parenteral
      nutrition resulted in improved nitrogen balance in septic rats: the cumulative
      nitrogen balance over the 4 days of treatment was positive in the rats given
      xylitol-supplemented parenteral nutrition and more positive when rats were
      treated with xylitol-glutamine-supplemented parenteral nutrition, as compared
      with other groups of septic rats. 4. The rate of loss of intracellular glutamine
      in skeletal muscle was markedly decreased (P less than 0.001) in response to
      xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 5.
      Hepatic protein and RNA contents were increased in septic rats treated with
      xylitol- and/or glutamine-supplemented parenteral nutrition. Similarly, protein
      and RNA contents were markedly increased in muscles of septic rats treated with
      xylitol- and/or glutamine-supplemented parenteral nutrition. 6. The rates of
      incorporation of leucine/tyrosine into liver/muscle proteins in vitro were
      increased and the rate of muscular tyrosine release was decreased in response to
      xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 7. It
      is concluded that the administration of xylitol- and/or glutamine-supplemented
      parenteral nutrition is beneficial to septic rats and possibly to septic
      patients.

PMID- 1374302
TI  - Pathogenesis of diabetic microangiopathy: the roles of endothelial cell and
      basement membrane abnormalities.

PMID- 1374303
TI  - Characterization of a chondroitin sulfate proteoglycan synthesized by monkey
      arterial smooth muscle cells in vitro.
AB  - A monoclonal antibody against arterial smooth muscle cell chondroitin sulfate
      proteoglycan has been developed. Incubation of [35S]-methionine labeled
      proteoglycans with MAb 941 quantitatively immunoprecipitated all the chondroitin
      sulfate proteoglycan (CSPG) synthesized by these cells. Digestion of the
      immunoprecipitate with chondroitin AC lyase revealed one major protein band (Mr
      420,000) and two minor bands (Mr 509,000 and 390,000) on SDS-PAGE that are
      composed of very similar peptides when analyzed by limited peptide digestion by
      S. aureus V8 protease. Additional studies demonstrated that this monoclonal
      antibody recognized an epitope on the chondroitin sulfate chains. However, only a
      minor subpopulation (5-12%) of the alkaline-borohydride released
      glycosaminoglycan chains was immunoprecipitated and this subset of chains was
      slightly larger than the non-immunoprecipitated chains. High pressure liquid
      chromatography analysis of the disaccharides generated from the
      immunoprecipitated glycosaminoglycan chains demonstrated that these chains were
      enriched in chondroitin-6-sulfate relative to chondroitin-4-sulfate (2:1) while
      that of the non-immunoprecipitated chains had a ratio of 1:1. These studies
      indicate that at least two distinct pools of chondroitin sulfate chains are
      present on all the chondroitin sulfate proteoglycan synthesized by arterial
      smooth muscle cells: a major population (89-95%) containing 6-sulfate and 4
      sulfate in relatively equal proportion and a minor population (5-12%) which is
      hydrodynamically larger with a 6-sulfate to 4-sulfate ratio of 2:1.

PMID- 1374304
TI  - Antibodies to defined histone epitopes reveal variations in chromatin
      conformation and underacetylation of centric heterochromatin in human metaphase
      chromosomes.
AB  - Unfixed metaphase chromosome preparations from human lymphocyte cultures were
      immunofluorescently labelled using antibodies to defined histone epitopes. Both
      mouse monoclonal antibody HBC-7, raised against the N-terminal region of H2B, and
      rabbit serum R5/12, which recognizes H4 acetylated at Lys-12, gave non-uniform
      labelling patterns, whereas control antibodies against total histone fractions H4
      and H1 produced homogeneous fluorescence. HBC-7 bound approximately uniformly to
      the bulk of the chromosomes, but the major heterochromatic domains of chromosomes
      1, 9, 15, 16 and the Y showed significantly brighter fluorescence. Serum R5/12
      indicated an overall reduction in acetylation of H4 in metaphase chromosomes
      compared with interphase nuclei, although some specific chromosomal locations had
      considerably elevated acetylation levels. Acetylation levels in the major
      heterochromatic domains appeared extremely low. To investigate further the
      differences noted in heterochromatin labelling, metaphases from cultures grown in
      the presence of various agents known to induce undercondensation of the major
      heterochromatic domains were similarly immunolabelled. Decondensed
      heterochromatin no longer exhibited higher than normal immunofluorescence levels
      with HBC-7. The higher resolution afforded by "stretching" the centromeric
      heterochromatin of chromosomes 1, 9 and 16 confirmed the low level of H4
      acetylation in these domains. We consider the implications of these observations
      in relation to chromatin conformation and activity.

PMID- 1374305
TI  - Flow cytometric analysis of proliferation associated nuclear antigens using
      washless staining of unfixed cells.
AB  - The expression of different proliferation associated nuclear antigens was
      analyzed using a washless double-staining method and flow cytometry. It is a
      simple and rapid two-step procedure which can be performed on low cell numbers. A
      series of hematopoietic cell lines and fresh lymphoma cells were tested and the
      methodology was found to be applicable to a number of nuclear antigens (PCNA, Ki
      67, p105, MPM-2, fibrillarin). For PCNA, the detectability was dependent on the
      type of antibody used. The immunofluorescence pattern observed by microscopy was
      altered for antigens stained by the washless technique in comparison with the
      pattern obtained with fixed cells. With the washless method, detailed cell cycle
      analysis could be obtained by dual parameter analysis of PCNA and Ki-67.

PMID- 1374306
TI  - Detection of viral surface antigens on HIV-2ben infected human tumor cell lines
      by flow cytometry.
AB  - The human monocytic cell line U-937 clone 2 and two T-cell lines CEM and MOLT-4
      clone 8 were infected with HIV-2ben, a recent isolate of HIV-2. Infection and
      subsequent antigen expression on the cell surface was monitored by flow cytometry
      using a rabbit-anti-serum against tween-ether-treated HIV-2ben and a fluorescein
      isothiocyanate-conjugated IgG against rabbit-IgG. The sensitivity of the three
      cell lines to infection with HIV-2ben correlated with the percentages of CD4
      expressing cells but not with the levels of CD4-expression on the cell. The
      appearance of viral surface antigens preceded the formation of syncytia and
      correlated closely with the infecting virus dose. After 1-2 weeks in culture, 20
      85% of the cells of each line expressed viral surface antigens. The variation
      depended on the cell type and cell culture conditions. The MOLT-4 clone 8 and the
      U-937 clone 2 cells died around 10 or 20 days, respectively, after HIV-2ben
      infection. Only HIV-2ben infected CEM cells grew permanently. Flow cytometry was
      an appropriate method to monitor the expression of viral proteins on the cell
      surface of HIV-infected cell lines. Flow cytometry proved to be more sensitive
      than determination of RT activity in supernatants of HIV-infected cells and more
      precise than light microscopy examinations.

PMID- 1374307
TI  - Quantitative and qualitative DNA variations in Anabaena azollae Strasb. living in
      Azolla filiculoides lam.
AB  - Heterocysts and vegetative cells of the filamentous nitrogen-fixing Anabaena
      azollae isolated from the apex to the basal leaf cavities of Azolla filiculoides
      were examined by epifluorescent microscope after fluorochrome staining. Acridine
      orange (AO), DAPI, and chromomycin fluorochromes were used in order to evidence
      total DNA content and respectively, A + T and G + C bases. Measurements of
      fluorescence intensities were made on photographic prints by the automatic image
      analysis system Quantimet 970. Heterocysts contained higher amounts of DNA than
      did vegetative cells, and their content strongly increased in the basal leaf
      cavities. The heterocyst DAPI brightness was quite uniform, whereas in vegetative
      cells DAPI brightness increased from the apex to the basal groups. In vegetative
      cells from the apex to the median group, the percentage of DAPI brightness was 60
      85% with respect to AO brightness, whereas in heterocysts of the same groups DAPI
      brightness was 40-50% with respect to AO brightness. In the basal group,
      brightness due to DAPI staining was comparable with those of previous group both
      in heterocysts and in vegetative cells, whereas chromomycin brightness increased
      strongly in heterocysts. These data show that heterocyst changes its DNA content
      and composition in the basal leaf cavities, suggesting that its lifetime is not
      completely over.

PMID- 1374308
TI  - Experimental and clinical evaluation by flow cytometry for the mechanism of
      combination therapy (cisplatin and peplomycin).
AB  - Pharmacologic effects of cisplatin (CDDP) and peplomycin (PEP) on tumor cell
      kinetics were studied both in vitro and in vivo with the aid of flow cytometry
      (FCM). Double staining with propidium iodide (PI) and fluorescein isothiocyanate
      (FITC)-labeled bromodeoxyuridine (BrdU) was used to analyze the cell cycle, and
      the number of viable cells was determined with fluorescein diacetate (FDA).
      Effects of combining the 2 agents were also studied to establish the most
      effective method of combination therapy. Furthermore, these agents were tried
      clinically on the basis of experimental results. Results showed that CDDP exerted
      its action at the S and G2M phases in the cell cycle and PEP at the G2M phase.
      Among the combination regimens in the experiments with CDDP, PEP, and CDDP + PEP
      as analyzed by FCM, the strongest block on the G2M phase was shown in the one at
      a 2-day interval, resulting in the most effective killing of the tumor cells.
      Clinical trial of the combination therapy showed the same results as the in vitro
      experiment; the therapy proved useful for improving the patient's clinical
      condition and the results obtained with CT imaging and pathology.

PMID- 1374309
TI  - [Enhancement of bleomycin or hyperthermia induced tumor cell damage by ADPRT
      inhibitor].
AB  - Enhancement of tumor cell damage by ADPRT inhibitor, 3-aminobenzamide (3AB) was
      investigated. 3AB could inhibit DNA strand break repair in HeLa S3 cells after
      treatment with bleomycin. 3AB was able to lower the clonogenic ability of HeLa S3
      cells after bleomycin treatment and hyperthermia. 3AB could also prevent
      potentially lethal damage repair (PLDR) in HeLa S3 cells treated with bleomycin.
      This work presents some experimental evidence and theoretical background for the
      possible use of 3AB as a sensitizer in the treatment of cancer.

PMID- 1374310
TI  - Decrease in plasma GLP-1 immunoreactivity in starved rats.
AB  - To determine whether starvation affects the metabolism of glucagon-like peptide-1
      (GLP-1), we measured the plasma levels of proglucagon-derived peptides and the
      biosynthesis and posttranslational processing of proglucagon in groups of six
      rats starved for 1, 3 and 5 days. The plasma levels of GLP-1 immunoreactivity
      (GLP-1 IR) and glucagon-like immunoreactivity (GLI) decreased during starvation
      reaching 79 and 56% of the respective control values by day 5 (P less than 0.05
      and less than 0.01 vs control). The same is true of the plasma IRI level. The
      ileal contents of GLP-1 IR and GLI were 50.8 +/- 3.8 pmol/g wet weight and 161.8
      +/- 13.2 pmol/g wet weight, respectively, on day 5 of starvation, which were
      significantly lower (P less than 0.01) than the respective values of 94.8 +/-
      16.6 pmol/g wet weight and 262.7 +/- 28.1 pmol/g wet weight in control rats.
      However, the pancreatic contents of proglucagon-derived peptides tended to
      increase during starvation, although their increases were not statistically
      significant. No significant change in the posttranslational processing of
      proglucagon was detected during starvation. The decrease in the ileal proglucagon
      derived peptides content was not associated with a decrease in intestinal
      proglucagon mRNA transcripts. These results suggested that decreased synthesis of
      proglucagon-derived peptides by the intestine was largely responsible for the
      reductions in their circulating levels in starved rats.

PMID- 1374311
TI  - Plasma neuropeptide Y (NPY) and galanin before and during exercise in type 1
      diabetic patients with autonomic dysfunction.
AB  - Plasma neuropeptide Y (NPY), plasma galanin and plasma catecholamines were
      determined before and during an ergometer exercise test in 11 type 1 diabetic
      patients (age 19-36 years, mean 30; duration of diabetes 2-18 years, mean 9) with
      autonomic dysfunction and in 13 age-matched healthy controls (age 24-36 years,
      mean 29). Before exercise, plasma NPY (100 +/- 6 pmol/l vs 144 +/- 7 pmol/l; P
      less than 0.001) and plasma galanin (54 +/- 3 pmol/l vs 77 +/- 5 pmol/l; P less
      than 0.005) were significantly lower in patients than in controls. During
      exercise, plasma NPY, plasma adrenaline, and plasma noradrenaline increased in
      patients and controls while galanin only increased in patients. Since there was a
      direct correlation between plasma NPY before exercise and the increment (delta
      80%) in noradrenaline during exercise (r = 0.54; P less than 0.01), it is
      suggested that plasma NPY determined in the basal situation may be a useful
      marker of sympathetic nerve failure in diabetic patients.

PMID- 1374312
TI  - Combined action of c-kit and erythropoietin on erythroid progenitor cells.
AB  - Mutations at the murine dominant-white spotting locus (W) (c-kit) affect various
      aspects of hematopoiesis. We have made antibodies against c-Kit with the
      synthetic peptides deduced from the murine c-kit gene and examined the role of c
      Kit in erythropoiesis. The antibody inhibited the stromal cell-dependent large
      colony formation of the erythroid progenitors. In the culture of erythropoietin
      responsive erythroid progenitors of the anemia-inducing Friend virus-infected
      mouse spleen, the antibody inhibited only proliferation, but not differentiation
      of the progenitor cells. The inhibition was effective only at the early phase
      (within 6 hours after erythropoietin addition) before the cells start to
      proliferate induced by erythropoietin. During the early phase, erythropoietin
      down-regulated c-kit gene expression. These results suggest a mechanism of
      combined action of c-Kit with erythropoietin on the lineage-restricted erythroid
      progenitor cells.

PMID- 1374313
TI  - Induction of dorsal and ventral mesoderm by ectopically expressed Xenopus basic
      fibroblast growth factor.
AB  - Peptide growth factors from the fibroblast growth factor (FGF) and transforming
      growth factor-beta families are likely regulators of mesoderm formation in the
      early Xenopus embryo. Although basic FGF is found in the Xenopus embryo at the
      correct time and at sufficient concentrations to suggest that it is the FGF-type
      inducer, the lack of a secretory signal sequence in the basic FGF peptide has
      raised questions as to its role in the inductive process. We show here that
      Xenopus basic FGF can ectopically induce mesoderm when translated from injected
      synthetic RNA within the cells of a Xenopus embryo. Basic FGF produced in this
      manner is able to induce the formation of both dorsal and ventral mesoderm with
      the type of mesoderm formed dependent on the inherent dorsal-ventral polarity of
      the animal hemisphere. Surprisingly, although Xenopus basic FGF produced from the
      injected mRNA has a potent mesodermalizing effect on animal hemisphere cells,
      virtually no phenotypic effect is observed with intact embryos. These results
      suggest that the role of Xenopus basic FGF is to specify the size of the marginal
      zone, and synergistically with a dorsally localized prepatterning signal, to
      initially establish the dorsal-ventral axis of the mesoderm.

PMID- 1374314
TI  - Expression of the IGFBP-2 gene in post-implantation rat embryos.
AB  - The insulin-like growth factors (IGFs) stimulate mitogenesis in a variety of cell
      types both in vitro and in vivo. These effects are mediated by both IGF receptors
      and a family of IGF binding proteins (IGFBPs), which are found complexed with the
      IGFs in serum and tissue fluids. Here we compare the sites of expression during
      early rat embryogenesis of the genes encoding the RGD-containing IGF binding
      protein IGFBP-2 and IGF-II. At all ages from early post-implantation through mid
      gestation, the expression of IGFBP-2 was highly complementary to IGF-II. IGFBP-2
      mRNA was detected throughout the epiblast of the egg cylinder as early as e7,
      when IGF-II expression was restricted to trophectoderm and other extraembryonic
      cells. As gastrulation proceeded, IGFBP-2 expression ceased as IGF-II expression
      began in the newly formed embryonic and extra-embryonic mesoderm, but was
      retained in other epiblast derivatives including the surface ectoderm and
      neuroectoderm, throughout its rostral-caudal extent. By e10-e11, IGFBP-2
      expression in neuroectoderm was restricted to the rostral brain of the primary
      neural tube and was found in the new population of neuroepithelium formed in the
      tail bud during secondary neurulation. IGFBP-2 expression remained high in the
      ventricular layer of the rostral brain into mid-gestation ages but decreased or
      disappeared as cells entered the mantle layer and began to express the
      neurofilament-related gene alpha-internexin. IGFBP-2 mRNA was abundant in surface
      ectoderm, particularly that of the branchial arches, and all ectodermal
      placodes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374316
TI  - Pharmacological agents affecting emesis. A review (Part I).
AB  - The availability of radiolabelled ligands selective for various putative
      neurotransmitter receptor sites and the development of quantitative
      autoradiography has led to a greater understanding of the neuronal pathway and
      receptor subtypes involved in the vomiting reflex induced by various mechanisms
      both within the central nervous system and the periphery. Receptors for
      acetylcholine, dopamine, histamine and serotonin have been detected in a number
      of brain regions associated with the vomiting reflex, and provide a rational
      basis for the antiemetic action of drugs that inhibit receptor subtypes for these
      neurotransmitters. The basis of the antiemetic action of other drugs such as
      dexamethasone and the cannabinoids is still obscure. Some drugs act on more than
      1 receptor subtype. Metoclopramide may inhibit both dopamine D2- and 5-HT3
      receptors in producing its antiemetic effect. Both metoclopramide and domperidone
      appear to have additional peripheral actions that contribute to their
      effectiveness. The cannabinoids are effective in cytotoxic-induced vomiting,
      perhaps acting via endorphin receptors or by inhibiting prostaglandin synthesis.
      The effectiveness of 5-HT3 receptor antagonists may depend on the block of both
      central and peripheral neuronal 5-HT3 receptors. Vomiting constitutes a major
      disadvantage to the use of many drugs; vomiting induced by aminoglycoside
      antibiotics appears to be due to ototoxicity and is relieved by histamine H1
      receptor antagonists. The protracted vomiting associated with the use of some
      cytotoxics in cancer chemotherapy may involve psychic components, the
      chemoreceptor trigger zone and peripheral sensory neurons. Both 5-HT3 and
      dopamine D2-receptor antagonists exert some control, the former being more
      effective with cytotoxics of high emetogenic potential, such as cisplatin.
      Serotonin 5-HT3 receptor antagonists or high doses of metoclopramide in
      combination with anxiolytics and steroids as well as greater attention to
      pharmacokinetic profiles of the drugs involved would appear to offer improved
      control. The use of dopamine receptor antagonists in controlling emesis induced
      by dopamine agonists used in Parkinson's disease poses theoretical problems which
      can be overcome by using drugs with selectivity for the chemoreceptor trigger
      zone, such as domperidone or metoclopramide. However, higher doses of these drugs
      may produce some impairment of therapeutic responses to the agonists. Muscarinic
      and nicotinic agonists currently under investigation in Alzheimer's disease pose
      another therapeutic dilemma as emesis is due to a central action of these
      compounds. Several sites may be involved including the chemoreceptor trigger zone
      and frontal lobes. Opiates may act through dopamine receptors or mu-receptors on
      dopaminergic nerves, but serotonergic mechanisms may also be involved in the
      action of some opiates.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374315
TI  - Interferons 1992. How much of the promise has been realised?

PMID- 1374317
TI  - Pharmacotherapy of ascites associated with cirrhosis.
AB  - Cirrhotic patients frequently develop ascites during the course of their disease.
      The appearance of ascites is the final consequence of profound disturbances in
      systemic and splanchnic haemodynamics, and in renal and hormonal function. The
      alterations in renal function consist of a decreased ability to excrete sodium
      and water, and in more severe cases, a reduction in renal blood flow and
      glomerular filtration rate. No effective drug therapy is yet available for water
      retention and renal failure in these patients. Sodium retention, however, may be
      treated by the administration of diuretics. The diuretics most commonly used in
      the treatment of cirrhotic patients with ascites are loop diuretics, particularly
      furosemide (frusemide), and distal, or 'potassium-sparing' diuretics such as
      spironolactone. Although furosemide has a much greater natriuretic potency than
      spironolactone in healthy individuals, studies in cirrhotic patients with ascites
      have shown that spironolactone is more effective than furosemide in the
      elimination of ascites. Nowadays, however, therapeutic paracentesis associated
      with plasma expanders has replaced diuretic therapy as the initial treatment for
      cirrhotic patients hospitalised with tense ascites since it is more effective and
      is associated with a lower rate of complications than diuretic therapy. Diuretics
      should be given after the elimination of ascites by paracentesis to avoid the
      reaccumulation of the abdominal fluid. Only cirrhotic patients with mild ascites
      should be treated initially with diuretics. Cirrhotic patients with ascites
      frequently develop a spontaneous infection of the ascitic fluid which is usually
      caused by Gram-negative bacilli from enteric origin and has a great tendency to
      recur after therapy. The antibiotics of choice for this infection are third
      generation cephalosporins. Long term administration of norfloxacin, which causes
      a selective elimination of Gram-negative bacilli from the intestinal flora, is
      effective in preventing the recurrence of ascites infection in these patients.
      Finally, cirrhotic patients with ascites are prone to develop renal failure when
      treated with a variety of pharmacological agents, particularly aminoglycosides
      and nonsteroidal anti-inflammatory drugs. The administration of the latter drugs
      may also cause dilutional hyponatraemia and refractory ascites since they induce
      water retention and impair the renal response to diuretics.

PMID- 1374318
TI  - Current role of chemotherapy in head and neck cancer.
AB  - Although cytotoxic chemotherapy is not fully established as an accepted part of
      the primary management of head and neck cancer, numerous studies over the past 10
      years have been undertaken, notably in the USA and Europe. Several classes of
      antineoplastic chemotherapy have activity and can induce tumour regression in
      patients with squamous or anaplastic cancers, the most common cell types. While
      response rates with newer combinations, such as cisplatin and fluorouracil, are
      reportedly as high as 90%, response duration is generally short-lived. The most
      promising use of chemotherapy appears to be synchronous or adjuvant therapy with
      radiotherapy and/or surgery. Combined modality therapy of this type is able to
      improve the local control rates; 2 prospectively randomised studies from the
      United Kingdom each with several hundred patients have suggested a possible
      improvement in overall survival as well. The most active agents are methotrexate,
      cisplatin, bleomycin and fluorouracil. Further studies are urgently needed to
      assess the true role of and the indications for chemotherapy, and because of the
      world-wide importance of these tumours, the identification of even a modest
      improvement would have profound benefit. The use of chemotherapy outside studies
      should still be discouraged.

PMID- 1374321
TI  - Calcipotriol. A review of its pharmacological properties and therapeutic use in
      psoriasis vulgaris.
AB  - Calcipotriol (calcipotriene) is a vitamin D3 analogue which inhibits epidermal
      cell proliferation and enhances cell differentiation. In patients with chronic
      plaque psoriasis involved in short term studies of 6 to 8 weeks' duration,
      calcipotriol ointment applied twice daily was significantly more effective than
      betamethasone valerate and dithranol (anthralin). Pooled data from clinical
      trials show that calcipotriol is well tolerated, with the majority of adverse
      events being mild and transient local reactions. Topically applied calcipotriol
      has low hypercalcaemic potential and, in contrast to topical corticosteroids,
      oral retinoids and orally administered calcitriol, methotrexate and cyclosporin,
      calcipotriol does not appear to be associated with a risk of serious adverse
      events. Thus, at this early stage in its clinical development, calcipotriol
      appears to be an effective and well tolerated topical therapy for the management
      of psoriasis; if promising preliminary clinical findings are confirmed,
      calcipotriol will represent a major advance in this difficult area of
      therapeutics.

PMID- 1374322
TI  - Potential sources of 1,2,8,9-tetrachlorodibenzo-P-dioxin in the aquatic
      environment.
AB  - A recent study reported elevated levels of 1,2,8,9-tetrachlorodibenzo-p-dioxin
      (1,2,8,9-TCDD) in crustaceans and finfish collected from Newark Bay, New Jersey
      (Rappe et al., 1989). The authors suggested that the presence of this compound in
      biota was due to operations at a former 2,4,5-trichlorophenoxy acetic acid (2,4,5
      T) manufacturing facility located on the lower Passaic River. Since 1,2,8,9-TCDD
      had been identified in two soil samples claimed to be associated with the site,
      it was concluded that the former manufacturing plant was the source of this
      compound. A review of the scientific literature was conducted to evaluate whether
      this isomer is associated with the formulation of 2,4,5-T and to determine
      whether 1,2,8,9-TCDD is commonly found in the aquatic environment. Measurements
      and chromatographic data from known sources of polychlorinated dibenzo-p-dioxins
      indicate that incinerator fly ash, soot from wood-burning chimneys, and the
      combustion of polychlorinated biphenyls and some chlorophenoxy herbicides are
      sources of 1,2,8,9-TCDD. This isomer has never been found in samples of 2,4,5-T.
      We conclude, therefore, that the presence of 1,2,8,9-TCDD in Newark Bay biota is
      not associated with 2,4,5-T manufacturers but, rather, the result of various
      commercial, residential, municipal, and industrial combustion processes.

PMID- 1374323
TI  - A scanning electron microscopic probe into the cellular injury in the alimentary
      canal of Notopterus notopterus (Pallas) after cadmium intoxication.
AB  - Microanatomical changes attributable to cadmium poisoning have been observed in
      the various regions of the alimentary tract of Notopterus notopterus after
      exposure to sublethal concentrations (75.54 mg CdCl2 liter-1) of the metal. In
      the buccopharynx, the major changes following treatment with cadmium were
      shrinkage of the stratified epithelial cells with shriveling of the microridges
      and loss of lateral contacts between neighboring epithelial cells. But the most
      pronounced effect was the aggravated secretion of mucin. The damage to the round
      or oval stratified epithelial cells in the esophagus was manifested by formation
      of an even sheet of microridges. In the stomach, the most conspicuous changes
      were the patchy necrosis of the columnar epithelial cells, fragmentation of
      microridges, and vigorous secretion of mucus from the apical portion of
      epithelial cells. Owing to cadmium treatment intestinal ceca exhibited disrupted
      mucosal folds with loss of the normal rectangular box-shaped arrangement. The
      columnar epithelial cells were found to lose their regular arrangement with an
      irregular positioning of the microridges within the cells after cadmium exposure.
      The mucosal folds of the anterior intestine became intensively disrupted with
      appreciable damage to the columnar epithelial cells. In the middle intestine the
      surface epithelial cells were adversely torn and the microvilli of the epithelial
      cells facing the lumen were heavily damaged. After cadmium exposure accelerated
      mucous cell activity in the intestine was distinct. No conspicuous changes were
      observed in the rectal portion after cadmium exposure, except for the
      disintegration of columnar epithelial cells and a concomitant release of large
      amounts of mucus into the lumen. All these findings suggest impaired digestion
      and absorption through the alimentary tract of the aforementioned fish.

PMID- 1374320
TI  - Controlled release metoprolol formulations. A review of their pharmacodynamic and
      pharmacokinetic properties, and therapeutic use in hypertension and ischaemic
      heart disease.
AB  - Conventional formulations of metoprolol have become well established in
      cardiovascular medicine and are particularly useful in the management of
      hypertension and ischaemic heart disease. Recently developed controlled release
      metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed
      to overcome the drug delivery problems of matrix-based sustained release forms by
      releasing the drug at a relatively constant rate over a 24-hour period, and thus
      producing sustained and consistent metoprolol plasma concentrations and beta 1
      blockade while retaining the convenience of once daily administration. Clinically
      and statistically significant reductions in blood pressure have been observed
      with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in
      mildly or moderately hypertensive patients. Studies in patients with mild to
      moderate hypertension have demonstrated that a similar or higher percentage of
      patients achieved a goal response with metoprolol CR/ZOK compared with matrix
      based sustained release formulations of metoprolol, or conventional atenolol or
      bisoprolol, while metoprolol OROS achieved an equal or greater response rate
      compared with conventional or matrix-based sustained release metoprolol
      preparations. In patients with stable effort angina pectoris, once daily
      administration of metoprolol CR/ZOK provided at least equal antianginal efficacy
      as conventional metoprolol in divided doses, while metoprolol OROS reduced the
      mean number of anginal attacks by the same margin as atenolol. Controlled release
      metoprolol formulations have been well tolerated in clinical trials. Metoprolol
      CR/ZOK was associated with a similar or lesser degree of adverse effects related
      to the central nervous system compared with atenolol or long acting propranolol.
      Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated
      bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue
      and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced
      bronchoconstrictor effects than atenolol, matrix-based sustained release
      metoprolol or long acting propranolol in patients with asthma or obstructive
      airways disease, and healthy volunteers. These results are presumably due to the
      beta 1-selectivity of metoprolol in addition to the relatively low plasma
      concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the
      avoidance of high peak plasma concentrations with these agents. Despite the
      relative safety of the controlled release forms of metoprolol, the use of all
      beta-adrenoceptor antagonists should be avoided in patients with a history of
      bronchospasm. Thus, controlled release metoprolol formulations offer the
      potential to maximise the confirmed benefits of this agent in the management of
      hypertension and angina, by maintaining clinically effective plasma
      concentrations within a narrow therapeutic range over a 24-hour dose interval.

PMID- 1374324
TI  - Screening methods for assessment of biodegradability of chemicals in seawater-
      results from a ring test.
AB  - An international ring test involving 14 laboratories was organized on behalf of
      the Commission of the European Economic Communities (EEC) with the purpose of
      evaluating two proposed screening methods for assessment of biodegradability in
      seawater: (a) a shake flask die-away test based primarily on analysis of
      dissolved organic carbon and (b) a closed bottle test based on determination of
      dissolved oxygen. Both tests are performed with nutrient-enriched natural
      seawater as the test medium and with no inoculum added other than the natural
      seawater microflora. The test methods are seawater versions of the modified OECD
      screening test and the closed bottle test, respectively, adopted by the
      Organization for Economic Cooperation and Development (OECD) and by the EEC as
      tests for "ready biodegradability." The following five chemicals were examined:
      sodium benzoate, aniline, diethylene glycol, pentaerythritol, and 4-nitrophenol.
      Sodium benzoate and aniline, which are known to be generally readily
      biodegradable consistently degraded in practically all tests, thus demonstrating
      the technical feasibility of the methods. Like in previous ring tests with
      freshwater screening methods variable results were obtained with the other three
      compounds, which is believed primarily to be due to site-specific differences
      between the microflora of the different seawater samples used and to some extent
      also to differences in the applied concentrations of test material. A positive
      result with the screening methods indicates that the test substance will most
      likely degrade relatively rapidly in seawater from the site of collection, while
      a negative test result does not preclude biodegradability under environmental
      conditions where the concentrations of chemicals are much lower than the
      concentrations applied for analytical reasons in screening tests. Nevertheless,
      the screening tests are considered useful and cost-effective tools for an initial
      assessment of biodegradability in marine environments.

PMID- 1374319
TI  - Enalapril. A reappraisal of its pharmacology and therapeutic use in hypertension.
AB  - Enalapril, an angiotensin converting enzyme (ACE) inhibitor usually administered
      orally once daily, decreases blood pressure by lowering peripheral vascular
      resistance without increasing heart rate or output. It is effective in lowering
      blood pressure in all grades of essential and renovascular hypertension. Patients
      not responding adequately to enalapril monotherapy usually respond with the
      addition of a thiazide diuretic (or a calcium antagonist or beta-blocker), and
      rarely require a third antihypertensive agent. Enalapril is at least as effective
      as other established and newer ACE inhibitors, and members of other
      antihypertensive drug classes including diuretics, beta-blockers, calcium
      antagonists and alpha-blockers, but therapy with enalapril may be less frequently
      limited by serious adverse effects or treatment contraindications than with other
      drug classes. The most frequent adverse effect limiting all ACE inhibitor therapy
      in clinical practice is cough. This favourable profile of efficacy and
      tolerability, and the substantial weight of clinical experience, explain the
      increasing acceptance of enalapril as a major antihypertensive treatment and
      supports its use as logical first-line therapeutic option.

PMID- 1374325
TI  - A comparative study of test methods for assessment of the biodegradability of
      chemicals in seawater--screening tests and simulation tests.
AB  - A comparative study has been performed on test methods for assessing the
      biodegradability of chemicals in seawater environments. A simple shake flask die
      away test with natural seawater and 14C-labeled chemicals added in
      microgram/liter concentrations is proposed as a "simulation" test. The analytical
      parameter used in this test is residual dissolved 14C activity. The performance
      of the simulation test has been compared with the performance of similar
      screening tests with dissolved organic carbon analysis and test compounds added
      in mg/liter concentrations to nutrient-enriched seawater. All chemicals
      investigated that passed the screening tests were also degradable in the
      simulation test and some results with simulation tests were positive; even
      screening tests were negative, while some compounds, including maleinhydrazide,
      known to be degradable in soil, remained undegraded in either type of test.
      Disappearance times after the ended lag time were smaller in screening tests than
      in simulation tests, but the rates of biodegradation cannot be meaningfully
      compared, as zero-order kinetics in combination with an exponentially growing
      population of degraders prevail in screening tests, while first-order kinetics
      and frequently a constant activity of degraders (cooxidation) prevail in
      simulation tests where the test material is a secondary substrate only. In
      screening tests, lag times are sometimes excessively long and highly variable.
      Whether the lag times could be decreased and their variability narrowed by
      supplementation with a cosubstrate (yeast extract) or by inoculation with
      seawater that had been preadapted to the test material was investigated. In most
      experiments such test modifications had no significant effect but in one
      experiment with 4-nitrophenol, inoculation with 1% preadapted seawater decreased
      the lag phase from greater than 35 to 9 days.

PMID- 1374326
TI  - Induction of micronuclei in hemocytes of Mytilus edulis and statistical analysis.
AB  - A genotoxicity test focusing on micronucleus production in the blood cells
      (hemocytes) of blue mussel M. edulis has been developed as a possible indicator
      for marine pollution. A linear dose-response relationship was found when M.
      edulis was exposed to low concentrations (0, 12.5, and 25 mg/liter) of the
      alkylating agent ethyl methanesulfonate under laboratory conditions, while higher
      concentrations (50 and 100 mg/liter) resulted in cytotoxic effects. Furthermore
      the micronuclei (MN) frequencies in wild mussels from four different field
      locations have been determined. Mussels collected from two polluted sites showed
      an elevated MN frequency, indicating the presence of genotoxic pollution. A
      method to determine the micronuclei background level is suggested and the further
      implications for applying the method in biomonitoring investigations are
      discussed. The considered M. edulis exhibits a high biological variation,
      emphasizing the importance of application of a correct statistical method. A
      systematic approach to the statistical evaluation of the mussel MN test is
      outlined. The statistical model includes three different situations: (a)
      estimation of parameters of a single sample, (b) estimation and comparison of two
      samples, and (c) estimation of a dose-response relationship. Cases (a) and (b)
      are especially relevant in biomonitoring investigations while case (c) primarily
      concerns laboratory experiments.

PMID- 1374327
TI  - Comparison of sublethal and lethal criteria for nine different chemicals in
      standardized toxicity tests using the earthworm Eisenia andrei.
AB  - In this study, the effects of nine different chemicals on the survival, growth,
      and reproduction of the earthworm species Eisenia andrei were determined using a
      recently developed method. Earthworms were exposed for 3 weeks to the test
      chemicals in an artificial soil substrate. Additional data on the acute toxicity
      of these chemicals were derived from the literature. For some chemicals, cocoon
      production was the most sensitive parameter (cadmium, chromium, paraquat, fentin,
      benomyl, phenmedipham), while for others cocoon hatchability was most sensitive
      (pentachlorophenol, parathion, carbendazim). In the case of parathion, growth of
      the worms seemed to be even more sensitive than reproduction. As an overall
      parameter for the effect on earthworm reproduction, the total number of juveniles
      produced per worm appeared to be a useful parameter. Differences between (acute)
      LC50 values and the lowest NOEC value for effects on growth and reproduction were
      different for each chemical. Difference was greatest for cadmium (a factor of
      greater than 100) and smallest for fentin, benomyl, and pentachlorophenol (a
      factor of 5-6).

PMID- 1374328
TI  - Validation of earthworm toxicity tests by comparison with field studies: a review
      of benomyl, carbendazim, carbofuran, and carbaryl.
AB  - To investigate whether results of laboratory toxicity tests with earthworms are
      capable of being used to predict effects in the field, a literature study was
      carried out. Benomyl, its metabolite carbendazim, carbofuran, and carbaryl were
      chosen as model substances. From data on the behavior of these pesticides in
      soil, it can be concluded that shortly after application most of the dosage will
      be in the top 2.5-cm soil layer. Soil concentrations can be estimated from field
      dosages used. Estimated field soil concentrations that affected earthworm
      populations were in agreement with effect levels determined in laboratory
      studies. In the field, species living in the surface layers (e.g., juveniles of
      many species) or coming to the soil surface to feed (e.g., Lumbricus terrestris)
      are most affected, since they experience a high degree of exposure. Evidently,
      species having long generation times need a relatively long time to recover. Both
      the distribution of the pesticide and the behavior of earthworms in soil affect
      earthworm exposure. Insight into these aspects may provide tools to predict both
      short- and long-term effects of pesticides on earthworm populations in field
      soils.

PMID- 1374329
TI  - Simultaneous and iterative weighted regression analysis of toxicity tests using a
      microplate reader.
AB  - A system is described for determination of LC50 or IC50 by an iterative process
      based on data obtained from a plate reader using a marine unicellular alga as a
      target species. The esterase activity of Tetraselmis suesica on fluorescein
      diacetate as a substrate was measured using a fluorescence titerplate.
      Simultaneous analysis of results was performed using an iterative process
      adopting the sigmoid function Y = y/1 (dose of toxicant/IC50)slope for dose
      response relationships. IC50 (+/- SEM) was estimated (P less than 0.05). An
      application with phosalone as a toxicant is presented.

PMID- 1374330
TI  - The uptake, metabolism, and biological half-life of benzo[a]pyrene administered
      by force-feeding in sea bass (Dicentrarchus labrax).
AB  - The kinetics of uptake and metabolism of benzo[a]pyrene (BaP) were studied in
      various tissues of a marine fish, the sea bass (Dicentrarchus labrax), after
      intragastric administration of pellets containing a 14C-labeled compound. Only
      25% of injected radioactivity was detected and it was found only in intestine,
      gallbladder, liver, and kidney. The major part of radioactivity was found in
      gallbladder (85% of the whole body radioactivity). The calculated half-lives
      determined after the decrease in radioactivity measured in these tissues were
      8.2, 3.5, 3.3, and 0.8 days for liver, gallbladder, intestine, and kidney,
      respectively. The kinetics of distribution of radioactivity between alkali and
      hexane tissue extracts showed the high metabolization potential of intestine
      which represents the main site of BaP uptake by this route of exposure. The other
      organs received mainly metabolites brought by general blood circulation.
      Intragastric administration as an experimental exposure route compared to other
      exposure patterns and particularly intraperitoneal injection, which has been used
      previously in the same species and under the same experimental conditions for the
      same kind of study, is discussed.

PMID- 1374331
TI  - Molecular characterization of the genomic regions of the Drosophila alpha-type
      subunit proteasome genes PROS-Dm28.1 and PROS-Dm35.
AB  - The proteasome (multicatalytic proteinase) consists of a large number of non
      identical protein subunits which are encoded by the evolutionarily conserved PROS
      gene family. Using the PROS-Dm35 and PROS-Dm28.1 cDNAs as probes, we have
      isolated the corresponding genomic DNA clones of Drosophila melanogaster. In situ
      hybridization shows that the members of the PROS gene family are not organized in
      a single gene cluster and that, in contrast to the PROS-Dm35 gene, the PROS
      Dm28.1 gene is localized on the X chromosome. Analysis of the genomic
      organization of the PROS-Dm28.1 and PROS-Dm35 genes reveals that both genes are
      interrupted by two small introns whereby the relative positions of the introns
      within the two coding regions are not conserved. Neither gene possesses a
      distinct transcriptional start site as shown by nuclease S1 analysis. Since the
      promoter regions also do not contain a TATA box, PROS genes appear to be typical
      house-keeping genes. A putative heat-shock element in the promoter region of the
      PROS-Dm35 gene was shown to be inactive on stress induction when fused to a
      reporter gene and tested in transient transfections assays. In addition, promoter
      deletion analysis demonstrates that the promoter region between positions -605
      and -330 contains sequence elements important for PROS-Dm35 gene activity and
      that deletions beyond position -150 result in an almost complete inhibition of
      transcription.

PMID- 1374332
TI  - cDNA and gene sequences of wheat chloroplast sedoheptulose-1,7-bisphosphatase
      reveal homology with fructose-1,6-bisphosphatases.
AB  - The nucleotide sequence encoding the chloroplast enzyme, sedoheptulose-1,7
      bisphosphatase [Sed(1,7)P2ase], was obtained from wheat cDNA and genomic clones.
      The transcribed region of the Sed(1,7)P2ase gene has eight exons (72-507 bp) and
      seven introns (85-626 bp) and encodes a precursor polypeptide of 393 amino acids.
      Comparison of the deduced amino acid sequence of Sed(1,7)P2ase with those of
      fructose-1,6-bisphosphatase [Fru(1,6)P2ase] enzymes from a variety of sources
      reveals 19% identity, rising to 42% if conservative changes are considered. Most
      importantly, the amino acid residues which form the active site of Fru(1,6)P2ase
      are highly conserved in the Sed(1,7)P2ase molecule, indicating a common catalytic
      mechanism. Interestingly, although the activities of both Sed(1,7)P2ase and
      chloroplast Fru(1,6)P2ase are modulated by light via the thioredoxin system, the
      amino acid sequence motif identified as having a role in this regulation in
      chloroplast Fru(1,6)P2ase is not found in the Sed(1,7)P2ase enzyme.

PMID- 1374333
TI  - Purification and membrane topology of PSI-D and PSI-E, two subunits of the
      photosystem I reaction center.
AB  - Structural studies have been conducted on polypeptides PSI-D and PSI-E, which are
      extrinsic but firmly bound to the photosystem I reaction center. These subunits
      are predicted to be involved in the correct interaction with soluble electron
      acceptor(s), like ferredoxin. We designed an original method to extract both
      polypeptides directly from thylakoid membranes and to purify them: a stepwise
      extraction with NaSCN followed by size fractionation and reverse-phase HPLC.
      Investigation of the in situ topology of PSI-D and PSI-E was undertaken using
      monoclonal antibody binding, controlled proteolysis, peptide sequencing and
      electron microscopy. The precise identification of numerous proteolytic sites
      indicates that the entire N-terminal regions of PSI-E (up to Glu15) and PSI-D (up
      to Lys15) are exposed to the medium. Partial mapping of the exposed epitopes was
      possible using purified fragments of each polypeptide. In the case of PSI-E, this
      mapping confirmed the accessibility of the N-terminal part, and suggested the
      need for another exposed sequence, probably located after Met39 in the second
      half of the protein. For PSI-D, this mapping revealed that the sequence between
      Met74 and Met140, including the most basic amino acid clusters, is also partly
      accessible. These experiments provide the first detailed informations, although
      still partial, on the topology of these polypeptides. They give a preliminary
      basis for hypotheses concerning the sites of interaction with the soluble
      counterparts.

PMID- 1374334
TI  - Increased steady-state levels of several mitochondrial and nuclear gene
      transcripts in rat hepatoma with a low content of mitochondria.
AB  - Cells from a rapidly growing rat Zajdela hepatoma were shown to contain (on a
      protein basis) five-times less mitochondria than hepatocytes from resting or
      regenerating rat liver. Transcripts of four nuclear genes for representative
      mitochondrial membrane proteins (beta-F1 subunit and N,N'-dicyclohexyl
      carbodiimide-binding protein of ATP synthase, subunit IV of cytochrome oxidase
      and ADP/ATP translocase) were present in 2-4 times higher amounts in the poly(A)
      rich RNA of the hepatoma than in the corresponding RNA fraction from resting or
      regenerating rat liver. The liver and hepatoma transcripts for the beta-F1
      subunit were translated in an in-vitro system with equal efficiency. Pulse-chase
      labeling of isolated Zajdela hepatoma cells and hepatocytes from resting and
      regenerating liver revealed a relative excess of the newly synthesized beta-F1
      subunit in the tumor cells. The half-life of the beta-F1 subunit was
      significantly shorter in the hepatoma cells than in hepatocytes from resting and
      regenerating liver. The contents of transcripts of three mitochondrial genes
      examined (cytochrome oxidase subunits I and II and NADH-ubiquinone reductase
      subunit 2) in Zajdela hepatoma mitochondria were about five-times higher than in
      the mitochondria of the resting cells and 3-4 times higher than in the organelles
      of the regenerating organ. The results indicate that events other than
      transcription (most likely post-translational) may be responsible for the reduced
      content of mitochondria in tumor cells.

PMID- 1374335
TI  - Adenosine(5')hexaphospho(5')adenosine stimulation of a Ca(2+)-induced Ca(2+)
      release channel from skeletal muscle sarcoplasmic reticulum.
AB  - Stimulation of a Ca(2+)-induced Ca(2+)-release channel from skeletal muscle
      sarcoplasmic reticulum by various adenosine(5')oligophospho(5')adenosines (ApnA,
      n = 2-6) by a rapid quenching technique using radioactive calcium was studied.
      Ap4A, Ap5A and Ap6A, as well as adenosine 5'-[beta, gamma-methylene]triphosphate
      (AdoPP [CH2]P), a non-hydrolyzable ATP analogue, stimulated the Ca(2+)-release
      channel, whereas Ap2A and Ap3A had no effect. At a concentration of 0.5 mM, the
      order of stimulation was AdoPP[CH2]P less than Ap4A less than Ap5A much less than
      Ap6A. As well as having the highest affinity (0.44 mM for half-maximal
      stimulation), Ap6A showed an extraordinarily high Hill coefficient of 3.3 (1.9
      for AdoPP[CH2]P, 2.1 for Ap5A). The stimulating effect of Ap6A was reversible,
      yet its dissociation proceeded very slowly. Stimulation of Ca2+ release by Ap6A
      was counteracted by Mg2+ and ruthenium red. A 2',3'-dialdehyde derivative of
      Ap6A, which is a chemical probe for amino groups, stimulated irreversibly the
      Ca(2+)-release channel and modified some high-molecular-mass sarcoplasmic
      reticulum proteins, possibly including the channel protein. Our data suggest that
      Ap6A stimulates the Ca2+ channel by binding to the activation site of the channel
      subunit and simultaneously preventing the spontaneous decay of the Ca2+ channel
      by keeping together two of the four channel subunits by bridging them with its
      two adenosine groups.

PMID- 1374336
TI  - Gamma delta T cells and the immune response in visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) caused by Leishmania donovani, a protozoan parasite,
      is a disease of high morbidity associated with hepatosplenomegaly,
      hypergammaglobulinemia, fever and death. One of the immunological hallmarks of VL
      is a remarkable increase in serum immunoglobulin levels as a result of polyclonal
      B cell activation. This study demonstrated that T lymphocytes expressing the T
      cell receptors (TcR) gamma delta in association with CD3 molecules are increased
      in circulation of patients with VL. A large proportions of TcR gamma delta
      bearing T cells had CD4+ CD8- phenotype, and expressed CD25, CD38, CD71 and HLA
      DR activation antigens. Furthermore, we demonstrated wide functional differences
      in TcR gamma delta and TcR alpha beta T cells in their proliferative response,
      secretion of interleukin-2 (IL-2), B cell growth factor (BCGF) and B cell
      differentiation factor (BCDF). It was of interest that the TcR gamma delta T
      cells from patients with VL could be expanded by in vitro culture with human
      recombinant IL-2. Although these TcR gamma delta T cells secreted diminished
      levels of IL-2, they produced highly augmented levels of both BCGF and BCDF,
      suggesting that secretion of these lymphokines in these T cell subsets is
      regulated independently. The relative increases in the CD4+ CDw29+ TcR gamma
      delta T cell subsets and their secretion of highly elevated levels of BCGF and
      BCDF largely accounted for the humoral immune system abnormality and
      hypergammaglobulinemia found in this disease. These observations may help to
      explain that TcR gamma delta T cells might be functional in vivo and are involved
      in immunological mechanisms of pathogenesis in VL.

PMID- 1374337
TI  - Immune regulation in self tolerance: functional elimination of a self-reactive,
      counterregulatory CD8+ T lymphocyte circuit by neonatal transfer of
      encephalitogenic CD4+ T cells lines.
AB  - Transfer of encephalitogenic, CD4+ T lymphocyte lines into syngeneic adult Lewis
      rats not only leads to the development of experimental autoimmune
      encephalomyelitis (EAE), but, in addition, to the expansion of counterregulatory,
      CD8+ T lymphocyte clones which are able to lyse specifically the encephalitogenic
      T cells in vitro and to neutralize their encephalitogenic capacity in vivo. In
      striking contrast, in neonatal rats, which still lack myelin (autoantigens),
      injection of the same encephalitogenic lines neither mediates EAE, nor confers
      protection in later life against the myelin-specific T cells. In fact, this
      treatment results in the life-long functional elimination of counterregulatory,
      clonotypic CD8+ T lymphocytes, which cannot even be reinduced by repeated
      injections of the relevant CD4+ T line. These data seem to point to a self
      protective T cell control mechanism which is developed within the immune system
      prior to, and thus independent of the appearance of the appropriate self antigen.

PMID- 1374338
TI  - Origin of CD5+ B cells and natural IgM-secreting cells: reconstitution potential
      of adult bone marrow, spleen and peritoneal cells.
AB  - The bulk of natural IgM secretion is currently attributed to peritoneal CD5+ B
      cells and their progeny, believed to be independent of adult bone marrow
      precursors. We have compared the capacity of peritoneal or splenic cells from
      normal adult mice to generate serum IgM after transfer into allotype-congenic,
      irradiated and bone marrow-protected mice. Recipients of either cell population
      produced donor-allotype IgM-secreting cells in the spleen, and had donor-derived
      serum IgM. In both cases as well, recipient IgM secretion recovered to control
      levels. Since the spleen cell-derived natural IgM production could result from
      expansion of CD5+ B cells present in the inoculum, we next investigated the
      ability of Ig- bone marrow (BM) cells (Ig- BM) to reconstitute natural IgM
      secretion in irradiated mice. This cell population was most efficient in
      reconstituting donor-derived IgM secretion. The origin and phenotype (IgM, CD5)
      of B cells present in spleen and peritoneum of recipient mice were also analyzed.
      In agreement with the high level of donor IgM-secreting cells, transfers of
      splenic and Ig- BM cells fully reconstitute donor B cells in spleen and
      peritoneum and inhibit reconstitution from host origin. In contrast, donor
      peritoneal cells reconstitute B cells very poorly in spleen and allow for
      reconstitution by host cells. Furthermore, Ig- BM cells as well as splenic or
      peritoneal donor cells, all reconstitute CD5+ B cells in the peritoneum of
      recipient mice. Interestingly, the fraction of IgM+ cells of each allotype that
      differentiate to IgM secretion varies widely, but normal levels of IgM are
      established even when the number of donor B cells present in the animal is very
      limited.

PMID- 1374339
TI  - Rapid activation-independent shedding of leukocyte L-selectin induced by cross
      linking of the surface antigen.
AB  - L-selectin (also termed LAM-1, Leu-8,TQ-1, gp90MEL-14, peripheral lymph node
      homing receptor and LECAM-1) is an adhesion protein thought to be important in
      leukocyte entry into lymphoid tissues and sites of inflammation. We, as well as
      others, have shown that leukocyte activation by chemotactic factors results in
      rapid shedding (release) of L-selectin from the cell surface. Here we have used
      flow cytometry, enzyme-linked immunosorbent assay, and SDS-PAGE/Western blot
      analysis to determine whether cross-linking of L-selectin in the absence of
      activation causes shedding. We found that rapid loss of leukocyte L-selectin
      expression (down-regulation) could be induced by treating cells with a chemical
      cross-linker [bis (sulfosuccinimidyl) suberate]. L-selectin down-regulation via
      cross-linking could occur at 4 degrees C and in the absence of detectable cell
      activation (increased expression of CD11b/18). The loss of L-selectin expression
      was due to shedding of the molecule from the leukocyte cell surface. Cross
      linking of L-selectin with specific monoclonal antibodies also caused loss of
      surface expression of L-selectin at 37 degrees C. Finally, shed L-selectin was
      detected in the plasma of healthy adults whose peripheral blood leukocytes
      demonstrated no obvious signs of activation. Our results suggest that activation
      independent shedding of leukocyte L-selectin may occur in vivo and a possible
      mechanism could involve cross-linking of leukocyte L-selectin. This provides a
      novel mechanism for rapid regulation of expression of a leukocyte-endothelial
      cell adhesion receptor.

PMID- 1374341
TI  - Hexadecylphosphocholine stimulates the colony-stimulating factor-dependent growth
      of hemopoietic progenitor cells.
AB  - The effect of the antitumorally active hexadecylphosphocholine (He-PC) on the
      colony-stimulating factor (CSF)-dependent growth of human hemopoietic progenitor
      cells was studied. At low concentrations He-PC stimulated the CSF-dependent
      progenitor cell colony growth of three patients suffering from chronic myeloid
      leukemia (CML) and of three of six patients without hematological disorders. The
      stimulating effect was up to eight times that of the control using granulocyte
      colony-stimulating factor (G-CSF) and twofold in the case of granulocyte
      macrophage colony-stimulating factor (GM-CSF), whereas only slight effects were
      noted when interleukin 3 (IL-3) or the combination of the CSFs was used as an
      additive. The stimulatory effects observed are far below the He-PC concentrations
      that are usually required for the in vitro growth arrest of cancer cells. At
      higher concentrations He-PC displayed suppressive effects, most pronounced in the
      case of G-CSF-dependent colony growth. At the concentrations investigated, He-PC
      failed to show any changes in the composition and distribution of specific
      colonies. He-PC by itself had no mitogenic activity. This indicates that He-PC
      acts as a co-stimulator. In the cases of myeloproliferative diseases and in the
      case of a patient without known hematological disorder, removal of accessory
      cells did not abrogate the He-PC-enhanced colony growth by CSFs. Thus, the
      stimulatory effect of low-dose He-PC seems not to be mediated by accessory cells.

PMID- 1374340
TI  - Among naive precursor cell subpopulations only progenitors of memory B cells
      originate germinal centers.
AB  - Immunization leads to the generation of both antibody-forming cells (AFC) and
      memory B cells which are thought to arise in germinal centers within lymphoid
      follicles. The findings that the precursors to memory B cells reside in the
      J11Dlo subpopulation of the spleens in non-immune mice and that this
      subpopulation is distinct from conventional AFC precursors, including CD5+ B
      cells, suggest that the precursors of germinal centers might also reside in the
      J11Dlo subpopulation. To test this hypothesis, SCID mice were repopulated with
      CD4+ carrier-primed T cells and T-depleted J11Dlo, J11Dhi or CD5+ B cells and
      immunized with a hapten-carrier conjugate. Only the J11Dlo population was
      enriched for cells that produced germinal centers. Thus, the subpopulation of
      precursors that generates memory B cells also originates germinal centers.

PMID- 1374342
TI  - Distribution of surface-membrane molecules on bone marrow and cord blood CD34+
      hematopoietic cells.
AB  - We have investigated the distribution of membrane molecules on CD34+
      hematopoietic cells isolated from human bone marrow (BM) and cord blood (CB). A
      distinct CD10+ population was present in BM, but it was not detected in CB. Most
      CD34+ CD10+ cells in BM were B-cell precursors (BCP), because they expressed
      CD19. However, CD40 and CD37 were found on the majority of CD34+ cells from
      either BM or CB, demonstrating that these antigens are not restricted to B
      lineage CD34+ cells. CD40 and CD37 were lost during culture of CD34+ cells in the
      presence of interleukin 3 (IL-3), indicating transient expression early in
      myeloid development. CD13 antigen was detected on virtually all CD34+ cells from
      BM and CB. Accordingly, CD13 was present on CD34+ CD10+ cells, demonstrating that
      this structure is not restricted to myeloid CD34+ cells. In contrast, myeloid
      CD33 antigen was not detected on CD34+ CD10+ cells. Expression levels of CD13 and
      of CD33 were heterogeneous in BM, reflecting diversity within the resident CD34+
      population. CD25 and CD71 were found on a proportion of CD34+ cells from either
      BM or CB and maintained during culture in IL-3, consistent with a distribution on
      activated cells. Finally, a variety of adhesion receptors were present on CD34+
      cells. These included the alpha 4 beta 1 (VLA-4), alpha 5 beta 1 (VLA-5), and
      alpha L beta 2 (LFA-1) integrins, as well as ICAM-1, LFA-3, H-CAM, and LAM-1.
      Expression of adhesion receptors was remarkably similar in BM and CB, and it
      followed an all-or-nothing pattern that failed to delineate CD34+ subsets. Taken
      together, our data show that although CD34+ cells from BM constitute a more
      heterogeneous population, resident and circulating CD34+ cells largely display
      the same cell-surface molecules.

PMID- 1374343
TI  - Effect of bryostatin 1 on the in vitro radioprotective capacity of recombinant
      granulocyte-macrophage colony-stimulating factor (rGM-CSF) toward committed human
      myeloid progenitor cells (CFU-GM).
AB  - We have examined the effect of the macrocyclic lactone protein kinase C (PK-C)
      activator bryostatin 1 on the in vitro radioprotective capacity of recombinant
      granulocyte-macrophage colony-stimulating factor (rGM-CSF) toward normal
      committed myeloid progenitor cells (day-14 granulocyte-macrophage colony-forming
      units [CFU-GM]). Preincubation of T-cell- and adherent cell-depleted bone marrow
      mononuclear cells with 12.5 nM bryostatin 1 and either 1.25 or 50 ng/ml rGM-CSF
      for 24 h resulted in an 18%-30% survival at 4-5 Gy, whereas cells exposed to rGM
      CSF alone gave rise to no detectable colonies at radiation doses greater than 2.5
      Gy. Coadministration of bryostatin 1 also led to a threefold increase in Do
      values for both rGM-CSF concentrations. A similar enhancement of radioprotective
      effects was observed with the tumor-promoting phorbol ester phorbol dibutyrate.
      Exposure of cells to both bryostatin 1 and rGM-CSF immediately following
      irradiation also resulted in enhanced progenitor cell survival when compared to
      rGM-CSF alone, but radioprotective effects were less than those observed when
      cells were preincubated with these factors. Cells preconditioned with bryostatin
      1 and rGM-CSF prior to exposure to 2 or 4 Gy gave rise to significantly more
      colonies when radiation was administered as a 4-h divided dose, suggesting that
      bryostatin 1 may act by potentiating rGM-CSF-induced repair of sublethal
      radiation damage. Finally, pre-exposure of enriched progenitor cells (CD34+) to
      bryostatin 1 and rGM-CSF resulted in radioprotective effects that were less than
      those observed for partially purified populations with respect to the total
      population of surviving myeloid colonies. However, CD34+ cells preincubated with
      bryostatin 1 and rGM-CSF prior to irradiation exhibited a significant increase in
      both the percentage and absolute number of neutrophilic and macrophage colonies,
      and a reduction in eosinophilic colonies, compared to cells exposed to rGM-CSF
      alone. These studies suggest that bryostatin 1 (and possibly other PK-C
      activators) potentiates the in vitro radioprotective effects of rGM-CSF and may
      also regulate the lineage specificity of this response.

PMID- 1374344
TI  - Four unique monoclonal antibodies to the putative receptor binding domain of
      erythropoietin inhibit the biological function of the hormone.
AB  - We have produced a series of monoclonal antibodies (MoAbs) to amino acid region
      99-129 of human erythropoietin (Epo) that distinguish unique structural features
      within this putative receptor binding domain of the hormone. The MoAbs recognize
      denatured Epo with widely different sensitivities on a Western blot and
      differentially bind to native Epo in solution. In addition, three of the four
      MoAbs neutralize the biological activity of Epo in a concentration-dependent
      fashion in vitro. Neutralization was measured both by inhibition of Epo-induced
      differentiation in Rauscher murine erythroleukemia cells and by inhibition of Epo
      induced proliferation in normal murine splenic erythroid precursors.
      Characterization of the structural epitopes recognized by each of these four
      reagent MoAbs should provide us with important information concerning the
      requirements for hormone-receptor interaction.

PMID- 1374345
TI  - Ultraviolet B-induced DNA fragmentation (apoptosis) in activated T-lymphocytes
      and Jurkat cells is augmented by inhibition of RNA and protein synthesis.
AB  - UVB (280-320 nm) light profoundly affects cellular immunity and immunogenicity.
      To further characterize the interaction of UVB light with T cells, we examined
      UVB-induced DNA fragmentation patterns in normal T cells and the T-cell line
      Jurkat. Resting or preactivated peripheral blood T cells from normal donors or
      Jurkat cells were exposed to various doses of UVB or gamma irradiation. Cells
      were sampled at 0-48 h after exposure, and DNA fragmentation was analyzed by
      electrophoresis in agarose gels. UVB and gamma irradiation, in a dose- and time
      dependent manner, induced DNA fragmentation in Jurkat cells and in T cells
      preactivated with phytohemagglutinin (PHA; 10 micrograms/ml) and phorbol
      myristate acetate (PMA; 10 ng/ml), but not in resting T cells. The presence of
      RNA or protein synthesis inhibitors such as actinomycin D or cycloheximide
      neither inhibited nor delayed DNA fragmentation; in fact, DNA fragmentation was
      augmented above control values. Similarly, DNA fragmentation increased in the
      presence of the calcium-chelating agent ethylene-glycol-bis-tetraacetic acid
      (EGTA) and decreased in the presence of the calcium ionophore A23187. In the
      presence of ethylenediaminetetraacetic acid (EDTA), DNA fragmentation decreased.
      In summary, these data show that UVB-induced DNA fragmentation strongly depends
      upon the cell activation status, and upon the presence of divalent cations other
      than calcium, possibly magnesium. The data indicate furthermore that in this
      model, inhibition of RNA or protein synthesis can induce rather than inhibit
      apoptosis, suggesting that the synthesis inhibitors disrupted primarily the
      synthesis or action of enzymes ordinarily aimed at repairing DNA fragmentation.

PMID- 1374346
TI  - The postnatal spatial and temporal development of corticospinal projections in
      cats.
AB  - Orthograde labeling and immunocytochemical techniques were used to study the
      postnatal spatial and temporal development of corticospinal projections in cats.
      Findings from the orthograde labeling studies indicate that there are three major
      phases in the spatial development of corticospinal projections: an early period
      (1-10 postnatal days) when cortical axons grow into the spinal gray from the
      white matter; an intermediate period (2-5 postnatal weeks) where corticospinal
      axons develop terminal arborizations in a rostral to caudal, medial to lateral
      and intermediate gray to dorsal and ventral horn sequence; and, a late period (6
      7 postnatal weeks) during which some corticospinal projections are eliminated.
      The time period over which cortical axons grow into the spinal cord was
      determined immunocytochemically using a monoclonal antibody against a microtubule
      associated protein (MAP 1B) present in growing axons. The corticospinal tracts
      were strongly immunoreactive for MAP 1B during the first three postnatal weeks.
      MAP 1B immunostaining of these tracts started to decline in the fourth postnatal
      week and was completely absent by five weeks of age. These findings indicate that
      the postnatal development of corticospinal projections is spatially and
      temporally protracted in cats.

PMID- 1374347
TI  - Retrograde transport of D-[3H]-aspartate injected into the monkey amygdaloid
      complex.
AB  - The possibility that certain of the afferents of the primate amygdaloid complex
      use an excitatory amino acid transmitter was evaluated by injecting D-[3H]
      aspartate into the amygdala of two Macaca fascicularis monkeys. The distribution
      of D-[3H]-aspartate labeled neurons was compared with those labeled with the
      nonselective retrograde tracer WGA-HRP injected at the same location as the
      isotope. Retrogradely labeled cells of both types were observed in a variety of
      cortical and subcortical structures observed in a variety of cortical and
      subcortical structures and in discrete regions within the amygdala. D-[3H]
      aspartate labeled neurons were observed in layers III and V of the frontal,
      cingulate, insular and temporal cortices. In the hippocampal formation, heavily
      labeled cells were observed in the CA1 region and in the deep layers of the
      entorhinal cortex. Of the subcortical afferents, the claustrum and the midbrain
      peripeduncular nucleus contained the greatest number of D-[3H]-aspartate labeled
      cells. Subcortical afferents that are not thought to use excitatory amino acids,
      such as the cholinergic neurons of the basal nucleus of Meynert, did not
      retrogradely transport the isotope. Within the amygdala, the most conspicuous
      labeling was in the paralaminar nucleus which forms the rostral and ventral
      limits of the amygdala. When the D-[3H]-aspartate injection involved the basal
      nucleus, many labeled cells were also observed in the lateral nucleus. Retrograde
      transport of D-[3H]-aspartate injected into the amygdala, therefore, appears to
      demonstrate a subpopulation of inputs that may use an excitatory amino acid
      transmitter.

PMID- 1374349
TI  - Accuracy of measurements of HbF with OSM3 in neonates and infants.
AB  - The accuracy of the Radiometer OSM3 oxymeter for measurement of fetal haemoglobin
      (HbF) in infants was investigated, and compared to one of the standard reference
      methods using alkali electrophoresis of haemoglobin. Blood samples of 37 infants
      with different gestational (27-41 weeks) and postnatal (1-198 days) ages were
      analysed. The two methods gave very close results but a significant mean
      difference (range -4.5-16.5%). However, agreement between the two methods was
      judged clinically acceptable (95% limits of agreement -7.5-15.5%). A rapid
      determination of HbF percentage, using OSM3, is an important determinant for
      correct assessment of oxygen saturation in newborn infants in intensive care
      units.

PMID- 1374348
TI  - GABAergic neuronal populations in monkey primary auditory cortex defined by co
      localized calcium binding proteins and surface antigens.
AB  - The primary auditory cortex (A1) of monkeys was investigated by
      immunohistochemistry, using antibodies to gamma-aminobutyric acid (GABA), to the
      calcium binding proteins parvalbumin and calbindin, and to certain proteoglycan
      epitopes. The two calcium binding proteins were found to be localized in
      subpopulations of GABAergic neurons. Parvalbumin immunoreactive cells were mostly
      found in the middle layers of the cortex. Parvalbumin immunoreactivity was found
      in fibres in the white matter underlying A1 and a particularly dense
      concentration of parvalbumin immunoreactive fibers and terminals occurred in
      layer IV suggesting that a significant population of geniculocortical fibers is
      also parvalbumin positive. Calbindin positive cells were mostly located in
      superficial layers and in these layers the neuropil staining was also dense. Two
      monoclonal antibodies (MAbs) raised against monkey brain tissue and which had
      previously been shown to recognize neuronal surface antigens stained overlapping
      subpopulations of GABAergic cells. Occasional pyramidal cells were also
      immunoreactive. Most of the MAb positive cells were found in the middle layers
      and all were parvalbumin but not calbindin immunoreactive. Although the
      physiological roles in the brain for calcium binding proteins and the relevant
      cell surface markers have not yet been clarified, the presence of these markers
      in selected subpopulations of cells suggests the existence of functionally
      distinct circuits in AI cortex.

PMID- 1374350
TI  - Expression of CSF-1/c-fms and SF/c-kit mRNA during preimplantation mouse
      development.
AB  - c-fms and c-kit are structurally related tyrosine kinase receptors for colony
      stimulating factor-1 (CSF-1) and for steel factor (SF), respectively. The level
      of c-fms mRNA, like c-kit mRNA, increases during the maturation of oocytes and is
      an abundant maternal message found in the unfertilized oocyte. Following
      fertilization, the level of both c-fms and c-kit oocyte mRNAs decreases rapidly
      until they are no longer detected by the early 2-cell stage. By the late 2-cell
      stage, both mRNAs are reexpressed, albeit at low levels. This low level of mRNA
      expression continues throughout preimplantation development. CSF-1 and SF
      transcripts are not detected in early preimplantation embryos, but are detected
      in cumulus cells, oviduct, and uterus, suggesting a paracrine action of these
      growth factors during the preimplantation period. The patterns of CSF-1/c-fms
      mRNA and SF/c-kit mRNA expression are consistent with the hypothesis that these
      two ligand/receptor systems may act in a compensatory or synergistic manner
      during preimplantation development.

PMID- 1374351
TI  - Temporal and quantitative analysis of myogenic regulatory and growth factor gene
      expression in the developing mouse embryo.
AB  - Using a reverse transcription/polymerase chain reaction method, the temporal
      pattern of expression of the myogenic regulatory genes (myf5, myogenin, MRF4, myo
      D) was quantitated in developing mouse muscle (whole embryo: 6.5 to 12.5 days
      postcoitum (dpc); front limb buds: 9.5 to 12.5 dpc; hind limb buds: 11.5 to 14.5
      dpc) and related to expression of TGF-beta 1, b-FGF, IGF-I, and IGF-II. Myf5 was
      the first myogenic regulatory factor to appear in both the whole embryo and front
      limb bud, with expression evident 7.5 and 9.5 dpc, respectively. A transient peak
      of MRF4 expression occurred 10.5 dpc in both the whole embryo and the front limb
      bud. Myogenin and myo D expression in the whole embryo was detected 8.5 and 9.5
      dpc, respectively. In the front limb bud myogenin and myo D expression was not
      detected until 10.5 dpc. In the hind limb bud myf5, myogenin, and MRF4 expression
      was detected 11.5 dpc. Myo D expression was not detected until 12.5 dpc. With
      respect to growth factor expression, in the front limb bud TGF-beta 1, IGF-I, and
      IGF-II were evident 9.5 dpc, while bFGF was not detected until 10.5 dpc. In the
      hind limb bud TGF-beta 1, bFGF, IGF-I, and IGF-II expression was detected 11.5
      dpc. These results show that in both the whole embryo and limb buds, all four
      myogenic regulatory factors are involved in the initiation of the myogenic
      program. We also show myf5 expression in the 9.5-dpc front limb bud, suggesting
      its expression in the somite-derived migrating muscle precursor cells.
      Correlations between growth factor-mediated myoblast proliferation and myogenic
      differentiation are discussed.

PMID- 1374352
TI  - Spatial, temporal, and hormonal regulation of epidermal keratin expression during
      development of the frog, Xenopus laevis.
AB  - To study the mechanism of hormone-induced keratin expression in the epidermis
      during Xenopus metamorphosis, a monospecific antibody was raised against a unique
      carboxy-terminal peptide of the 63-kDa keratin. Immunohistological analysis
      demonstrated that the onset of 63-kDa keratin expression showed distinct regional
      and temporal differences. The expression started at stage 54 in the hindlimb
      epidermis, at stage 57 in the head, and over 1 month later at stage 63 in the
      tail. The amount of 63-kDa keratin was further regulated during epidermal
      stratification and differentiation. The 63-kDa keratin was expressed first in
      basal epidermal cells before stratification began. The outer layer of the larval
      epidermis (periderm) did not express the 63-kDa keratin. As the cells moved out
      of basal layer, they stained more intensely with the anti-keratin antibody
      indicating that 63-kDa keratin synthesis is up-regulated during differentiation.
      Similar results were obtained with cultures of purified epidermal cells grown in
      high calcium conditions. Since we have shown that thyroid hormone (T3) induces 63
      kDa keratin gene expression and hydrocortisone (HC) modulates T3 action we
      examined the effects of T3 and HC at the single cell level with the anti-keratin
      antibody. Immunostaining demonstrated that T3 alone and T3 plus HC increased the
      number of 63-kDa keratin-positive cells as well as the amount of 63-kDa keratin
      per cell. Unexpectedly these hormones had the same effects on head and tail
      epidermal cells even though the latter cells degenerate during metamorphosis. The
      major difference between tail and head cells was that the percentage 63-kDa
      keratin-producing cells was much greater in the head than in the tail.

PMID- 1374353
TI  - Development of substance P receptors on rat motoneurons in vitro.
AB  - Experiments were performed to examine the influence of interneuronal interactions
      on the expression of neurotransmitter receptors by developing mammalian CNS
      neurons. Receptors for the neuropeptide, substance P (SP), were assayed on
      embryonic rat motoneurons and other spinal cord neurons developing in vitro by
      the binding of 125I-SP to live neurons. Scatchard analysis showed the presence of
      high-affinity binding sites, and binding competition assays using SP, neurokinin
      A, or neurokinin B indicated that the high-affinity 125I-SP binding sites on
      these neurons were type NK1 tachykinin receptors, or SP receptors (SPRs). Neurons
      in the spinal cords of rats at Embryonic Day 14 displayed no SPRs. Cell-surface
      SPRs were detected on spinal cord neurons within 24 hr after they were placed in
      culture, however, and the level of 125I-SP binding increased for several days.
      SPRs were assayed on spinal motoneurons that had been identified by retrograde
      labeling with a fluorescent tracer, isolated in high purity by fluorescence
      activated cell sorting (FACS), and maintained in culture. Motoneurons grown in
      isolation from other neurons developed SPRs in vitro along the same time course
      as neurons in heterogeneous spinal cord cultures. These results show that rat
      spinal motoneurons can express SPRs early in their development, and they suggest
      that the initial expression of SPRs by developing motoneurons does not require
      interaction with other neurons.

PMID- 1374354
TI  - Expression of the myogenic gene MRF4 during Xenopus development.
AB  - In a search for myogenic genes in Xenopus, I have cloned homologs of the
      mammalian myogenic genes MRF4 and myogenin. The myogenin clone is a genomic
      fragment encoding an amino acid sequence with 62% identity to the N-terminal
      region of rat myogenin. No myogenin transcript has been detected and no cDNA has
      been isolated, suggesting that Xenopus myogenin, if it is expressed at all, is
      likely to be expressed at low levels or transiently during development. A Xenopus
      MRF4 cDNA has been isolated and encodes an amino acid sequence with 72% identity
      to rat MRF4. In adult frogs, MRF4 RNA is detectable only in skeletal muscle
      (whereas MyoD, unexpectedly, is also expressed at low levels in the heart).
      During embryonic development, MRF4 RNA appears later than MyoD, at a time when
      the embryonic musculature already shows many differentiated features. This
      implies that MRF4 is not involved in the commitment or early differentiation of
      muscle cells. The accumulation of Xenopus MRF4 RNA overlaps with the formation of
      neuromuscular connections, suggesting that it may be induced by innervation.
      Consistent with this possibility, the level of Xenopus MRF4, but not MyoD, RNA is
      reduced in response to denervation of adult frog muscle.

PMID- 1374355
TI  - Peritoneal absorption of pancreatic enzymes in dogs.
AB  - To elucidate peritoneal absorption of pancreatic enzymes, plasma levels of
      amylase, lipase, and trypsinogen were measured after the intraperitoneal
      injection of 10 ml human pancreatic juice in dogs. Plasma pancreatic amylase,
      lipase, and trypsinogen were determined using the immunoassay specific to the
      corresponding human pancreatic enzyme to exclude cross-reaction with the
      endogenous enzyme activities of the canine plasma. Plasma immunoreactivity of
      human amylase persistently rose during 24 h after the injection, whereas
      elevation of plasma amylase enzyme activity become significant only at 24 h.
      Increase of plasma lipase was not remarkable. Significant increase of the
      immunoreactivity was observed only at 24 h but there was no significant increase
      of the enzyme activity during this period. Plasma trypsinogen immunoreactivity
      peaked at 2 h remained significantly elevated during 24 h. The transperitoneal
      absorption of pancreatic enzymes in dogs was confirmed using intraperitoneal
      injection of human pancreatic juice combined with immunoassay specific to human
      pancreatic enzymes.

PMID- 1374357
TI  - Interesting problems in enteroviral inflammatory heart disease.
AB  - Enteroviral inflammatory heart disease is an established entity. Based upon the
      accumulated work from many laboratories, specific and definitive questions can be
      posed regarding the pathogenic nature of the viruses involved and how the host
      immune systems respond to the insult of enterovirus replication in the
      myocardium. The answers to these questions may well lead to efficient
      intervention therapies such as vaccination or effective anti-viral compounds,
      thus eradicating enterovirus-induced heart disease. Understanding the nature of
      the acute disease is the first requirement toward a complete understanding of the
      mechanisms at work in chronic inflammatory heart disease.

PMID- 1374356
TI  - Expression of tenascin and fibronectin in the rabbit cornea after excimer laser
      surgery.
AB  - In order to investigate the effects of excimer laser surgery on corneal wound
      healing, 25 rabbits underwent anterior keratectomy at a depth of 100 or 300
      microns with a Meditec MEL 50 excimer laser. After various intervals the animals
      were killed and the cornea excised and investigated immunohistochemically for the
      expression of extracellular matrix (ECM) proteins, fibronectin and tenascin.
      Fibronectin was shown to occur earlier than tenascin, and the two also had
      different distribution patterns. Wound depth showed no clear effect on the
      localization and time of ECM protein expression. This study indicates that
      corneal wounds caused by excimer laser radiation and those caused by mechanical
      surgery differ as to healing mechanisms.

PMID- 1374358
TI  - Laminin and type VII collagen distribution in different types of human lung
      carcinoma: correlation with expression of keratins 14, 16, 17 and 18.
AB  - The expression patterns of basement membrane components and keratin intermediate
      filament proteins were studied in normal human bronchial epithelium and 56 lung
      carcinomas using monoclonal antibodies to laminin, type VII collagen and the
      individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII
      collagen were present between the epithelium and the lamina propria of bronchi
      and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the
      basal and some suprabasal cells and keratin 18 in the columnar cells of the
      bronchi and bronchioles. Keratin 16 was not present in normal bronchial
      epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII
      collagen was present only in squamous cell carcinomas, where it showed a
      reduction in expression with decreasing differentiation. Type VII collagen was
      not identified in adenocarcinomas, small cell carcinomas or carcinoids.
      Antibodies to basal cell keratins 14 and 17 also displayed positivity only in
      squamous cell carcinomas, although no correlation with the degree of
      differentiation could be observed. Keratin 16 appeared to be a marker of the
      squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for
      columnar epithelial cells showed a reaction pattern opposite to that of the basal
      cell keratins, being extensively present in adenocarcinomas, small cell
      carcinomas and carcinoids, with less expression in squamous cell carcinomas. This
      study shows a correlation between the presence of type VII collagen and the basal
      cell keratins 14 and 17, and a negative correlation between these components and
      keratin 18. These findings are likely to be useful in identifying lung cancer
      subtypes.

PMID- 1374359
TI  - Dystrophic amyloidosis.

PMID- 1374360
TI  - A rare MspI RFLP of the DMD probe p20 (DXS269).

PMID- 1374361
TI  - A 22-bp deletion in the coding region of the cystic fibrosis gene.

PMID- 1374362
TI  - The activation of major histocompatibility complex class I genes by interferon
      regulatory factor-1 (IRF-1).
AB  - We have investigated the role of interferon regulatory factor-1 (IRF-1), an
      interferon-gamma (IFN-gamma) inducible transcriptional activator, on major
      histocompatibility complex (MHC) class I gene transcription. IRF-1 alone is
      sufficient to trans-activate both transfected and endogenous class I genes and
      the effect of IRF-1 appears to be direct and sequence-specific. These data
      suggest that IRF-1 is involved in the IFN-gamma mediated induction of MHC class I
      expression.

PMID- 1374363
TI  - Expression of alternatively spliced HLA class II transcripts in lymphoid and
      nonlymphoid tissues.

PMID- 1374364
TI  - Orientation of the myelin proteolipid protein C-terminus in oligodendroglial
      membranes.
AB  - The topology of the integral membrane proteolipid protein (PLP) has important
      structural and functional implications for central nervous system myelin. To
      determine the orientation of the carboxyl-terminal portion of PLP, cultured mouse
      oligodendrocytes were probed with polyclonal antibodies raised against a
      synthetic terminal peptide corresponding to PLP residues 264-276 and with ten
      separate monoclonal antibodies that react with this region. Cells were examined
      by double-label indirect immunofluorescence for the presence of the PLP C
      terminus and either oligodendrocyte-specific surface or intracellular antigens.
      To detect surface antigens, both living and paraformaldehyde-fixed cells were
      incubated with primary antibodies and then stained with fluorochrome-conjugated
      second antibodies. Antigens located within the cytoplasmic space were identified
      after fixation and permeabilization of cells. Live-labeled oligodendrocytes were
      stained brightly for myelin-oligodendrocyte glycoprotein, galactocerebroside, and
      other surface markers but did not stain for the PLP C-terminus or the
      intracellular proteins myelin basic protein and beta-tubulin. Fixation alone was
      sufficient for partial permeabilization of oligodendrocytes to antibodies and
      resulted in limited staining of the PLP C-terminus and intracellular proteins.
      The permeabilized oligodendrocytes stained intensely for the PLP C-terminus,
      myelin basic protein, and beta-tubulin. Finally, trypsinization of living
      oligodendrocytes eliminated surface myelin-oligodendrocyte glycoprotein staining
      but did not change the immunostaining properties of the PLP C-terminus. These
      results provide evidence that the carboxyl-terminus of PLP is located at the
      cytoplasmic face of oligodendroglial membranes.

PMID- 1374365
TI  - Occupational exposure of truck drivers to dust and polynuclear aromatic
      hydrocarbons: a pilot study in Geneva, Switzerland.
AB  - The exposure to dust and polynuclear aromatic hydrocarbons (PAH) of 15 truck
      drivers from Geneva, Switzerland, was measured. The drivers were divided between
      "long-distance" drivers and "local" drivers and between smokers and nonsmokers
      and were compared with a control group of 6 office workers who were also divided
      into smokers and nonsmokers. Dust was measured on 1 workday both by a direct
      reading instrument and by sampling. The local drivers showed higher exposure to
      dust (0.3 mg/m3) and PAH than the long-distance drivers (0.1 mg/m3), who showed
      no difference with the control group. This observation may be due to the fact
      that the local drivers spend more time in more polluted areas, such as streets
      with heavy traffic and construction sites, than do the long-distance drivers.
      Smoking does not influence exposure to dust and PAH of professional truck
      drivers, as measured in this study, probably because the ventilation rate of the
      truck cabins is relatively high even during cold days (11-15 r/h). The
      distribution of dust concentrations was shown in some cases to be quite different
      from the expected log-normal distribution. The contribution of diesel exhaust to
      these exposures could not be estimated since no specific tracer was used.
      However, the relatively low level of dust exposure dose not support the
      hypothesis that present day levels of diesel exhaust particulates play a
      significant role in the excess occurrence of lung cancer observed in professional
      truck drivers.

PMID- 1374366
TI  - Provocation testing of human sperm motility using energy substrates and
      activators of the cyclic nucleotide system. I. Establishment of conditions for
      response testing.
AB  - In order to establish a series of provocation tests to evaluate the integrity of
      the sperm cAMP pathway, manganese (Mn), 2-deoxyadenosine (DEA) (via adenylyl
      cyclase), and methyl-isobutyl-xanthine (MIX) (via phosphodiesterase) were tested
      for their capacity to activate the progressive motility of human sperm. Optimal
      responses were obtained using washed sperm previously incubated for 3 hours in
      substrate-poor medium (Hepes-buffered saline). Longer periods of incubation
      required the presence in addition of an energy substrate such as glucose.
      Exposure of sperm to seminal plasma for 24 hours prior to washing attenuated the
      responsiveness of the sperm to the different activators. Preliminary studies on
      the activation of the progressive motility of washed sperm from four
      normozoospermic men under fertility investigation, prepared under identical
      conditions, revealed differences in the pattern of response which may have
      pathophysiological relevance.

PMID- 1374367
TI  - Surgical removal of submacular hemorrhage and subfoveal choroidal neovascular
      membranes.

PMID- 1374368
TI  - Immunohistochemical staining patterns of benign breast biopsies by 323/A3 and Ca1
      monoclonal antibodies related to epidemiological and radiological risk criteria.
AB  - Monoclonal antibodies 323/A3 and Ca1 have been suggested as markers of breast
      cancer risk in benign breast disease. We have studied the staining profiles in
      benign biopsies of 323/A3 and Ca1 in 146 patients. We then compared the staining
      patterns grouped according to whether the patients were at "high or low" risk of
      breast cancer by conventional epidemiological or radiological criteria. The
      results show that the staining profiles are similar between risk groups and that
      on the risk criteria used in this study 323/A3 and Ca1 will not distinguish
      patients at risk of developing breast cancer.

PMID- 1374369
TI  - Annulate lamellae: a last frontier in cellular organelles.

PMID- 1374370
TI  - [Multiple angiolipomas--analgesics therapy with doxepin].
AB  - Angiolipomas are rare benign tumours of the subcutaneous fat; they are sometimes
      solitary but their occurrence is more frequently multiple. Angiolipomas can be
      differentiated from lipomas clinically by their pronounced tenderness and
      histologically by their variable vascularization. The disease occurs mostly in
      young adults, the sites of predilection being the trunk and proximal extremities.
      Multiple angiolipomas have to be differentiated from other lipomatoses,
      especially from adiposis dolorosa (Dercum's disease). The case reported in this
      paper was characterized by typical clinical and histological findings. The
      systemic administration of acetylsalicylic acid, diclofenac, ketotifen,
      ranitidine, tramadol, tilidine combined with naloxone did not provide adequate
      pain relief. In contrast, the therapeutic efficiency of the antidepressant
      doxepin, which also displays antihistaminic effects, suggests a possible role of
      mediators in the development of pain in angiolipomas.

PMID- 1374371
TI  - Autoradiography of lymph nodes with 99mTc-dextran in rabbits.
AB  - 99mTc-dextran (D) was further evaluated in the present study as a
      lymphoscintigraphic agent compared to radiocolloids. It was injected intra
      dermally into the web space between the second and third toes in both hind feet
      of two rabbits. 99mTc-nanocolloid (NC) was injected subcutaneously in both hind
      feet of two other rabbits. Popliteal lymph nodes were taken out and frozen in
      liquid nitrogen after the animals were sacrificed at 2 h post-injection. Three
      frozen sections in 10 microns thickness were prepared from each node for
      autoradiographic studies. The lymph node slices were exposed for 18 h using
      Ilford G 5 emulsion. The obtained autoradiographs showed that the distribution of
      99mTc-D radioactivity within lymph nodes was more uniform indicating better
      tissue penetration compared to 99mTc-NC which remained mostly in the lymph
      canaliculi.

PMID- 1374372
TI  - Alternating laminated array of two types of mucin in the human gastric surface
      mucous layer.
AB  - Attempts have been made to develop a procedure for preserving and analysing the
      surface mucous layer of the human stomach in paraffin sections. Histologically
      normal gastric mucosae were obtained from 20 surgically removed stomachs. Of the
      different fixatives tested, Carnoy's solution gave rise to the most satisfactory
      results. In Haematoxylin-Eosin stained sections, the surface mucous layer
      appeared as a thick eosinophilic layer coating the gastric mucosal surface and
      measured 55.4 +/- 2.5 microns in the fundus and 21.8 +/- 1.0 microns in the
      pylorus respectively. A dual staining method consisting of galactose oxidase-cold
      thionine Schiff and paradoxical concanavalin A staining was applied to the
      surface mucous layer in order to reveal the distribution pattern of mucins
      secreted by two types of mucous cell in the gastric mucosa: surface mucous cells
      and gland mucous cells. As a result of this staining, an alternating laminated
      layer was visualized which consisted of the particular two types of mucin. In
      five cases, the surface mucous layer was examined in unfixed frozen sections.
      This layer was only partially preserved but revealed the same laminated
      structure. These results indicated that gland mucous cell mucins contribute to
      form the surface mucous layer.

PMID- 1374373
TI  - KS-505a, a novel inhibitor of bovine brain Ca2+ and calmodulin-dependent cyclic
      nucleotide phosphodiesterase from Streptomyces argenteolus.
AB  - A novel compound, KS-505a was isolated from the culture broth of a strain
      identified as Streptomyces argenteolus A-2. The compound inhibited bovine brain
      Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase with an IC50
      value (the concentration causing 50% inhibition) of 0.065 microM. The compound
      around that concentration had little or no effect on heart calmodulin-dependent
      and -independent cyclic-nucleotide phosphodiesterases, and protein kinase C.

PMID- 1374374
TI  - A new angiogenesis inhibitor, FR-111142.
AB  - FR-111142 is a new angiogenesis inhibitor produced by a fungus Scolecobasidium
      arenarium F-2015. FR-111142 inhibited endothelial cell proliferation in vitro and
      angiogenesis in the growing chick chorioallantoic membrane model in vivo.
      Further, FR-111142 also suppressed the solid tumor growth in mice.

PMID- 1374375
TI  - Effects of bleomycin on growth kinetics and survival of Saccharomyces cerevisiae:
      a model of repair pathways.
AB  - In order to analyze the roles of some repair genes in the processing of bleomycin
      induced DNA damage and, especially, the interrelationships among the involved
      repair pathways, we investigated the potentially lethal effect of bleomycin on
      radiosensitive mutants of Saccharomyces cerevisiae defective in recombination,
      excision, and RAD6-dependent DNA repair. Using single, double, and triple rad
      mutants, we analyzed growth kinetics and survival curves as a function of
      bleomycin concentration. Our results indicate that genes belonging to the three
      epistasis groups interact in the repair of bleomycin-induced DNA damage to
      different degrees depending on the concentration of bleomycin. The most important
      mechanisms involved are recombination and postreplication repair. The initial
      action of a potentially inducible excision repair gene could provide intermediate
      substrates for the RAD6- and RAD52-dependent repair processes. Interaction
      between RAD6 and RAD52 genes was epistatic for low bleomycin concentrations. RAD3
      and RAD52 genes act independently in processing DNA damage induced by high
      concentrations of bleomycin. The synergistic interaction observed at high
      concentrations in the triple mutant rad2-6 rad6-1 rad52-1 indicates partial
      independence of the involved repair pathways, with possible common substrates. On
      the basis of the present results, we propose a heuristic model of bleomycin
      induced DNA damage repair.

PMID- 1374376
TI  - Electrophoretic and chemical characterization of lipopolysaccharides of Vibrio
      parahaemolyticus.
AB  - Lipopolysaccharides (LPSs) isolated from three Kanagawa-positive and three
      negative strains of Vibrio parahaemolyticus were characterized by using
      electrophoretic, immunochemical, and chemical methods. The results of this study
      indicated that the LPSs of all six strains of V. parahaemolyticus examined did
      not have an O-specific side chain. These V. parahaemolyticus LPSs appeared to
      have molecular weights similar to that of the rough-type (Ra) LPS of Salmonella
      typhimurium TV-119 and might just contain lipid A and a core region. However, the
      microheterogeneity of V. parahaemolyticus LPS observed was greater than that of
      S. typhimurium LPS. The profile of V. parahaemolyticus LPS consisted of closely
      spaced triplet or quadruplet bands, but that of S. typhimurium consisted of
      doublet bands. Slower-moving bands appeared on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gels only when large amounts of V.
      parahaemolyticus LPS were loaded. These bands were proven to be the aggregates of
      the fastest-moving low-molecular-weight bands by re-electrophoresis. The banding
      pattern of V. parahaemolyticus LPSs produced on nitrocellulose membranes by
      immunoblotting indicated that the V. parahaemolyticus LPSs did not have an O
      specific side chain. The low ratio of total carbohydrate to lipid A of V.
      parahaemolyticus LPSs also suggested that they were like rough-type LPS. The
      mobility and profile of V. parahaemolyticus LPS on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gel and its chemical composition were closely
      related to the serotype of a specific strain but not with the Kanagawa
      phenomenon.

PMID- 1374377
TI  - Interaction of the heat shock protein GroEL of Escherichia coli with single
      stranded DNA-binding protein: suppression of ssb-113 by groEL46.
AB  - Previous studies from our laboratory have shown that an allele of the heat shock
      protein GroEL (groEL411) is able to specifically suppress some of the
      physiological defects of the single-stranded DNA-binding protein mutation ssb-1.
      A search for additional alleles of the groE genes which may act as suppressors
      for ssb mutations has led to the identification of groEL46 as a specific
      suppressor of ssb-113. It has very little or no effect on ssb-1 or ssb-3. All of
      the physiological defects of ssb-113, including temperature-sensitive growth,
      temperature-sensitive DNA synthesis, sensitivity to UV irradiation, methyl
      methanesulfonate, and bleomycin, and reduced recombinational capacity, are
      restored to wild-type levels. The ssb-113 allele, however, is unable to restore
      sensitivity of groEL46 cells to phage lambda. The mechanism of suppression of ssb
      113 by groEL46 appears to differ from that of ssb-1 by groEL411. The data suggest
      that GroEL may interact with single-stranded DNA-binding protein in more than one
      domain.

PMID- 1374378
TI  - Effects of inducing expression of cloned genes for the F0 proton channel of the
      Escherichia coli F1F0 ATPase.
AB  - To evaluate whether expression of cloned genes for the F0 proton channel of the
      Escherichia coli F1F0 ATPase is sufficient to cause membrane proton permeability,
      plasmids carrying different combinations of the uncB, E, and F genes, encoding
      the a, c, and b subunits of the F0 sector, cloned behind the inducible lac
      promoter in pUC9 or pUC18, were constructed. The effects of inducing F0 synthesis
      in an unc deletion strain were monitored by measuring cell growth rate,
      quantitating F0 subunits by immunoblotting, and measuring the ability of
      membranes to maintain a respiration-induced proton gradient and to bind F1 and
      carry out energy-coupling reactions. The levels of functional reconstitutable F0
      in membranes could be increased four- to sixfold with no change in cellular
      growth rate or membrane proton permeability (assayed by fluorescence quenching).
      These results were obtained in uninduced cultures, so the F0 genes were
      presumably being transcribed from some promoter besides lac. Induction of
      transcription of all three F0 genes produced increased amounts of F0 subunits in
      membranes as determined by immunoblot and F1-binding assays, but, when
      reconstituted with F1, the F0 in membranes isolated from induced cultures was
      significantly less functional than the F0 in membranes isolated from uninduced
      cultures. Such induction did result in growth inhibition, but there was no
      correlation between growth inhibition and either increased membrane proton
      permeability or the presence of functional, reconstitutable F0.

PMID- 1374379
TI  - Folding and oxidation of recombinant human granulocyte colony stimulating factor
      produced in Escherichia coli. Characterization of the disulfide-reduced
      intermediates and cysteine----serine analogs.
AB  - The folding and oxidation of recombinant human granulocyte colony-stimulating
      factor solubilized from Escherichia coli inclusion bodies was investigated.
      During the folding process, two intermediates, I1 and I2, were detected by
      kinetic studies using high performance liquid chromatography. I1 exists
      transiently and disappears quickly with the concomitant formation of I2. In
      contrast, I2 requires a longer time to fold into the final oxidized form, N.
      CuSO4 catalysis increases the folding rate of I2 from I1, while CuSO4 and
      elevated temperature (37 degrees C) have a dramatic effect on the folding rate of
      N from I2. These observations suggest the following sequential oxidative folding
      pathway. [sequence: see text] Peptide map analysis of the iodoacetate-labeled
      intermediates revealed that I1 represents the fully reduced granulocyte colony
      stimulating factor containing 5 free cysteines; I2 is the partially oxidized
      species containing a single Cys36-Cys42 disulfide bond; and N, the final folded
      form, has two disulfide bonds. The physicochemical properties and biological
      activities of I1, I2, N, and several Cys----Ser analogs made by site-directed
      mutagenesis were further investigated. In guanidine hydrochloride-induced
      denaturation studies, the disulfide-reduced intermediates and the analogs missing
      either of the disulfide bonds are conformationally less stable than those of the
      wild type molecule or the analog with the free Cys at position 17 changed to Ser.
      Recombinant human granulocyte colony stimulating factor lacking either disulfide
      bond or both has overall secondary and tertiary structures different from those
      of the wild type molecule and exhibits lower biological activity. These studies
      show that disulfide bond formation is crucial for maintaining the molecule in a
      properly folded and biologically active form.

PMID- 1374380
TI  - A role for the Na/K-ATPase in the control of human c-fos and c-jun transcription.
AB  - The c-fos proto-oncogene is known to be regulated by a variety of hormones,
      growth factors, and other conditions that alter cellular metabolism. The
      regulation of c-fos RNA concentrations is known to occur both by altered RNA half
      life and/or changes in the transcription rate of the gene. In most cases thus far
      investigated, induction of c-fos transcription by growth factors occurs very
      rapidly and transiently. Results presented in this paper show that ouabain, a
      specific inhibitor of the Na/K-ATPase increases the transcription of c-fos, as
      well as c-jun, in a variety of cultured cells. However, in contrast to other
      agents that induce c-fos and c-jun expression, the increased transcription rate
      of these genes in the presence of ouabain required several hours and remained
      elevated for at least 16 h. NIH 3T3 cells that have been transfected with
      deletions of the human c-fos promoter have enabled us to define at least two
      elements within the promotor that are regulated by ouabain. These include the
      serum response element and a region between 123 and 222 base pairs 5' to the
      start site of transcription. We speculate that regulation of the intracellular
      ion balance through changes in Na/K pump activity may be a general mechanism by
      which basal transcriptional activity of c-fos is modulated.

PMID- 1374381
TI  - Modulation of the mitochondrial cyclosporin A-sensitive permeability transition
      pore by the proton electrochemical gradient. Evidence that the pore can be opened
      by membrane depolarization.
AB  - This paper reports an investigation on the relationship between the proton
      electrochemical gradient (delta mu H+) and the cyclosporin A-sensitive
      permeability transition pore (PTP) in rat liver mitochondria. Using the SH group
      cross-linker phenylarsine oxide as the inducer, we show that both matrix pH and
      the membrane potential can modulate the process of PTP induction independently of
      Ca2+. We find that membrane depolarization induces the PTP per se when pHi is
      above 7.0, while at acidic matrix pH values PTP induction is effectively
      prevented. Since Ca2+ uptake leads to major modifications of the delta mu H+
      (i.e. matrix alkalinization and membrane depolarization), we have explored the
      possibility that the Ca(2+)-induced changes of the delta mu H+ may contribute to
      PTP induction by Ca2+. Our data in mitochondria treated with Ca2+ plus N
      ethylmaleimide and Ca2+ plus phosphate show that membrane depolarization is a
      powerful inducer of the PTP. Taken together, our observations indicate that the
      PTP can be controlled directly by the delta mu H+ both in the absence and
      presence of Ca2+, and suggest that a collapse of the membrane potential may be
      the cause rather than the consequence of PTP induction under many experimental
      conditions. Thus, many inducers may converge on dissipation of the membrane
      potential component of the delta mu H+ by a variety of mechanisms.

PMID- 1374382
TI  - Interactions of diphtheria toxin B-fragment with cells. Role of amino- and
      carboxyl-terminal regions.
AB  - The B-fragment of diphtheria toxin binds to cell surface receptors and
      facilitates entry of the enzymatically active A-fragment into the cytosol. The
      roles of the amino- and carboxyl-terminal regions of the B-fragment in
      interactions with the cell membrane were studied by measuring specific binding,
      insertion into membranes at low pH, and formation of cation-selective channels,
      as well as by toxicity measurements after association with active A-fragment.
      Deletion of the amino-terminal 12 amino acids of the B-fragment did not affect
      its ability to bind to receptors and to form ion channels at low pH, whereas both
      abilities were strongly impaired when one more amino acid (Trp206) was removed.
      Replacement of the amino-terminal 31 residues with an amphipathic sequence from
      human apolipoprotein A1 restored receptor binding but not ion channel formation.
      The binding to cells was virtually abolished when 9 residues were deleted from
      the carboxyl terminus. Deletion of only 4 residues or extension by 12 residues
      did not prevent specific binding, but reduced insertion, channel formation, and
      toxicity. Those deletions that reduced receptor binding ability increased the
      trypsin sensitivity of the B-fragment. The results indicate that the amino- and
      carboxyl-terminal regions of diphtheria toxin B-fragment are important for
      receptor binding, possibly because they contribute to keep the B-fragment in a
      binding-competent conformation. Small alterations in the carboxyl-terminal end
      reduced insertion, channel formation, and toxicity more than the ability of the B
      fragment to bind to cells.

PMID- 1374383
TI  - A novel mechanism for controlling the activity of alpha 2-macroglobulin
      receptor/low density lipoprotein receptor-related protein. Multiple regulatory
      sites for 39-kDa receptor-associated protein.
AB  - The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related
      protein (alpha 2MR/LRP) consists of two polypeptides, 515 and 85 kDa, that are
      noncovalently associated. A 39-kDa polypeptide, termed the receptor-associated
      protein (RAP), interacts with the 515-kDa subunit after biosynthesis of these
      molecules and remains associated on the cell surface. This molecule regulates
      ligand binding of alpha 2MR/LRP (Herz, J., Goldstein, J. L., Strickland, D. K.,
      Ho, Y. K., and Brown, M. S. (1991) J. Biol. Chem. 266, 21232-21238). Titration
      and binding studies indicate that RAP binds to two equivalent binding sites on
      alpha 2MR/LRP, with a KD of 14 nM. Heterologous ligand displacement experiments
      demonstrated that RAP completely inhibits the binding of 125I-activated alpha 2M
      to human fibroblasts and to the purified alpha 2MR/LRP, with a Ki of 23 and 26
      nM, respectively. A direct correlation between the degree of binding of RAP to
      the receptor and the degree of ligand inhibition was observed, indicating that as
      the RAP binding sites are saturated, alpha 2MR/LRP loses its ability to bind
      ligands. Thus, the amount of RAP bound to alpha 2MR/LRP dictates the level of
      receptor activity. A model is proposed in which alpha 2MR/LRP contains multiple
      ligand binding sites, each regulated by a separate RAP site.

PMID- 1374384
TI  - The matrix metalloprotease matrilysin (PUMP) is expressed in developing human
      mononuclear phagocytes.
AB  - Matrilysin (PUMP, MMP-7) is a member of the metalloprotease gene family, whose
      constituents are responsible for the remodeling of extracellular matrix. The
      matrilysin protein is a 28-kDa zymogen possessing catalytic activities against a
      broad range of extracellular matrix substrates including proteoglycans, gelatin,
      fibronectin, laminin, and elastin. To gain insights into the biological
      expression of matrilysin in human cell types, we generated a monospecific,
      polyclonal antibody against a 16-amino acid sequence derived from its catalytic
      domain, a region which lacked significant homology with other matrix
      metalloenzymes. We found this antibody capable of precipitating a 28-kDa protein
      from the conditioned media of human bone marrow-derived promonocytes and human
      peripheral blood monocytes cultivated in vitro. Promonocyte matrilysin was
      rapidly converted to a 19-kDa form by organomercurial activation. While
      matrilysin was constitutively synthesized by bone marrow-derived promonocytes,
      its secretion was markedly up-regulated by the mononuclear phagocyte activator,
      lipopolysaccharide. Furthermore, despite its expression in monocyte precursors,
      blood monocytes, and monocyte-derived macrophages, matrilysin was not synthesized
      by human alveolar macrophages under any tested condition. In situ hybridization
      studies with matrilysin cRNA confirmed the presence of specific mRNA in both
      human promonocytes and monocytes. Moreover, a marked increase in hybridizable
      mRNA was observed with lipopolysaccharide treatment suggesting that matrilysin
      synthesis is pretranslationally regulated. In summary, this represents the first
      report documenting constitutive and regulated synthesis of matrilysin by a normal
      human cell type and suggests that matrilysin is expressed as a significant
      secreted product of mononuclear phagocytes at an intermediate stage of cellular
      differentiation.

PMID- 1374385
TI  - The human leukocyte platelet-activating factor receptor. cDNA cloning, cell
      surface expression, and construction of a novel epitope-bearing analog.
AB  - A human myeloid transcript of approximately 4 kilobases was cloned as a cDNA from
      an expression library based on homology with the guinea pig cDNA recently
      described by Honda et al. (Honda, Z-I., Nakamura, M., Miki, I., Minami, M.,
      Watanabe, T., Seyama, Y., Okado, H., Tok, H., Ito, K., Miyamato, T., and Shimizu,
      T. (1991) Nature 349, 342-346) as a receptor for platelet-activating factor
      (PAF). The cloned DNA confers high affinity binding sites for platelet-activating
      factor when transfected into COS-7 cells and has binding and desensitization
      properties similar to the human leukocyte receptor. Southern analysis using this
      cDNA indicates that the PAF receptor gene is present as a single copy in the
      human genome. The deduced protein sequence predicts seven hydrophobic regions for
      the PAF receptor, characteristic of the rhodopsin gene family, and is 83%
      identical to the deduced protein sequence of the corresponding guinea pig
      molecule. A modified human PAF receptor cDNA was constructed by inserting an
      additional 30 nucleotides after the 5'-ATG, encoding the amino acid sequence
      MDYKDDDDKEF, which is specifically recognized by a monoclonal antibody. The
      modified cDNA encodes a functional PAF receptor and is detected by antibody on
      the membrane of transfected COS-7 cells. The use of this construct supports the
      structural model for the rhodopsin-like superfamily of receptors which places the
      NH2-terminal sequence on the extracellular side of the membrane, and should
      additionally be useful for affinity purification of the receptor protein.

PMID- 1374386
TI  - Human cysteine-rich protein. A member of the LIM/double-finger family displaying
      coordinate serum induction with c-myc.
AB  - We previously reported the structure of the placentally derived human cysteine
      rich (h crp) cDNA and demonstrated that it encodes a highly conserved and widely
      distributed zinc finger-like protein. We now report that the expression of both
      the mouse and human crp genes is induced as a primary response to serum in
      quiescent Balb/c 3T3 cells and in human fibroblasts. The profile of this primary
      response is remarkably parallel to that of c-myc in the Balb/c 3T3 cell line. The
      structure of the 23.2-kilobase h crp gene demonstrates that it is a member of a
      gene superfamily encoding proteins sharing a highly characteristic 52-amino acid
      "LIM/double-finger" motif. The evolutionarily conserved structure of cysteine
      rich protein, its structural similarity to a number of developmentally critical
      proteins, its distinctive tissue distribution, and its primary response to early
      events in the cell cycle suggest that crp plays an important role in cell
      function.

PMID- 1374387
TI  - The alpha subunit of meprin A. Molecular cloning and sequencing, differential
      expression in inbred mouse strains, and evidence for divergent evolution of the
      alpha and beta subunits.
AB  - Meprin A, a membrane-bound oligomeric metalloendopeptidase, contains two
      different subunits, alpha and beta. We report here the cloning and sequencing of
      the alpha subunit cDNA. The translated polypeptide consists of 760 amino acids,
      including a preprosequence (77 amino acids) that precedes the NH2 terminus of the
      purified enzyme. The next 198 amino acids constitute the "astacin family"
      protease domain, which includes the astacin family signature sequence,
      HE(L,I)XHXXGFXHE(Q,H)XRXDRDX(Y,H)(V,I)X(I,V). An immunoglobulin/major
      histocompatibility complex protein signature was found at the end of the protease
      domain. At the COOH terminus of the alpha subunit, there is an epidermal growth
      factor-like domain, followed by a transmembrane domain, and six additional amino
      acids. Ten potential glycosylation sites have been identified, and at least three
      of those sites are glycosylated. Northern blot analyses of kidney tissue from
      C57BL/6 and C3H/He mice indicate that variations in meprin A activity in these
      strains reflect differences in the levels of the alpha subunit mRNA. Several
      internal peptide sequences obtained from the beta subunit indicate that it is
      approximately 50% identical to the alpha subunit. Furthermore, NH2-terminal
      sequence analyses (39 residues) indicate that rat and mouse alpha are 79%
      identical, rat and mouse beta are 74% identical, and that alpha and beta subunits
      for both species are 47% identical. These data indicate that alpha and beta are
      closely related products of divergent evolution.

PMID- 1374388
TI  - Human adipsin is identical to complement factor D and is expressed at high levels
      in adipose tissue.
AB  - A cDNA for human adipsin was isolated and shown to encode a protein sharing 98%
      amino acid sequence similarity with the protein sequence previously determined
      for purified natural human complement factor D. Like mouse adipsin, recombinant
      human adipsin displays the enzymatic activity of human complement factor D,
      cleaving complement factor B only when B is complexed with activated complement
      component C3. We conclude that human adipsin is equivalent to complement factor D
      and that adipsin is the homologue of factor D in rodents. Adipose tissue is a
      major site of synthesis of human adipsin/complement factor D mRNA, but unlike the
      case in rodents, human adipsin mRNA is also expressed in monocytes/macrophages.
      The data presented here, demonstrating the equivalence of human adipsin to
      complement factor D and its high level of expression in fat, suggest a previously
      unsuspected role for adipose tissue in immune system biology.

PMID- 1374389
TI  - Beta 1,4-galactosyltransferase: a short NH2-terminal fragment that includes the
      cytoplasmic and transmembrane domain is sufficient for Golgi retention.
AB  - Beta 1,4-galactosyltransferase (beta 1,4-GT) is a Golgi-resident, type II
      membrane-bound glycoprotein that functions in the coordinate biosynthesis of
      complex oligosaccharides. Additionally, beta 1,4-GT has been localized to the
      cell surface of a variety of cell types and tissues where it is proposed to
      function in intercellular recognition and/or adhesion. Thus beta 1,4-GT is an
      appropriate molecule to be used in analyzing the molecular basis for retention of
      a membrane-bound enzyme in the Golgi complex and its subsequent or alternative
      transport to the cell surface. Previously we have shown that the gene for bovine
      and murine beta 1,4-GT is unusual in that it specifies a short (SGT) and long
      (LGT) form of the enzyme (Russo, R. N., Shaper, N. L., and Shaper, J. H. (1990)
      J. Biol. Chem. 265, 3324-3331). The only difference between the two related forms
      is in the primary structure of the cytoplasmic domains, where LGT has an NH2
      terminal extension of 13 amino acids. In this study, we have tested the
      hypothesis that LGT and SGT are differentially retained in the Golgi or directed
      to the cell surface. LGT, SGT or chimeric proteins, containing the NH2-terminal
      cytoplasmic and transmembrane domain of SGT and LGT fused to the cytoplasmic
      protein pyruvate kinase, were each stably expressed in Chinese hamster ovary
      cells. Proteins expressed from each construct were localized by
      immunofluorescence staining exclusively to a perinuclear region, identified as
      the Golgi by co-localization with wheat germ agglutinin. Furthermore, the
      subcellular distribution of both SGT and LGT was restricted to the trans-Golgi
      compartment as assessed by EM immunoelectron microscopy. These data suggest that
      both forms of beta 1,4-GT are resident trans-Golgi proteins and that an NH2
      terminal segment containing the cytoplasmic and transmembrane domains of SGT (39
      amino acids) or LGT (52 amino acids) is sufficient for Golgi retention.

PMID- 1374390
TI  - A cardiac troponin T epitope conserved across phyla.
AB  - Troponin T is a thin filament protein that is important in regulating striated
      muscle contraction. We have raised a monoclonal antibody against rabbit cardiac
      troponin T, monoclonal (mAb) 13-11, that recognizes its epitope in cardiac
      troponin T isoforms from fish, bird, and mammal but not from frog. The number of
      these isoforms expressed in cardiac muscle varies among species and during
      development. Cardiac troponin T isoforms were not found in adult skeletal muscle,
      while they were expressed transiently in immature skeletal muscle. We have mapped
      the epitope recognized by mAb 13-11 using rabbit cardiac troponin T isoforms.
      Analysis of stepwise cyanogen bromide digestion, which allowed association of the
      epitope to regions spanning methionine residues, coupled with immunoactivity of
      synthetic peptides, corresponding to sequences containing methionine residues,
      indicated that mAb 13-11 recognized its epitope in a 17-residue sequence
      containing the methionine at position 68, SKPKPRPFMPNLVPPKI. Comparison of
      skeletal and cardiac troponin T sequences suggested that the epitope was
      contained within the sequence FMPNLVPPKI. Synthetic peptides PFMPNLVPPKI and
      FMPNLVPPKI were recognized by mAb 13-11 on slot-blots. Enzyme-linked
      immunosorbent assay demonstrated mAb 13-11 recognized, in order of descending
      affinity, the 17-, 11-, and 10-residue sequence. Preabsorption of mAb 13-11 with
      each of these sequences blocked the recognition of the 17-residue peptide by mAb
      13-11. The domain, PFMPNLVPPKI is encoded by the 5' region of the cardiac gene
      exon 10 and is present in hearts across a broad range of phyla. These findings
      suggest that this cardiac troponin T-specific sequence confers onto myofilaments
      structural and functional properties unique to the heart.

PMID- 1374391
TI  - Molecular cloning and nucleotide sequence of cDNA encoding human muscle glycogen
      debranching enzyme.
AB  - cDNA comprising the entire length of the human muscle glycogen debranching enzyme
      was cloned and its nucleotide sequence determined. The debrancher mRNA includes a
      4545-base pair coding region and a 2371-base pair 3'-nontranslated region. The
      calculated molecular mass of the debrancher protein derived from cDNA sequence is
      172,614 daltons, consistent with the estimated size of purified protein (Mr
      165,000 +/- 500). A partial amino acid sequence (13 internal tryptic peptides
      with a total of 213 residues) determined on peptides derived from purified
      porcine muscle debrancher protein confirmed the identity of the cDNA clone.
      Comparison of the amino acid sequence predicted from the human glycogen
      debrancher cDNA with the partial protein sequence of the porcine debrancher
      revealed a high degree (88%) of interspecies sequence identity. RNA blot analysis
      showed that debrancher mRNA in human muscle, lymphoblastoid cells, and in porcine
      muscle are all similar in size (approximately 7 kilobases). Two patients with
      inherited debrancher deficiency had a reduced level of debrancher mRNA, whereas
      two other patients had no detectable abnormality in RNA blots. The isolation of
      the debrancher cDNA and determination of its primary structure is an important
      step toward defining the structure-function relationship of this multifunctional
      enzyme and in understanding the molecular basis of the type III glycogen storage
      disease.

PMID- 1374392
TI  - Cloning and sequencing of a rabbit cDNA encoding an intestinal and kidney
      specific Na+/H+ exchanger isoform (NHE-3).
AB  - We previously cloned, sequenced, and expressed two distinct mammalian Na+/H+
      exchanger isoforms (NHE-1 and NHE-2). We report here the cloning of a composite
      cDNA which encodes a third mammalian isoform (NHE-3), which is expressed
      specifically in intestine and kidney. The protein deduced from the longest open
      reading frame of this composite sequence has 832 amino acids with a calculated Mr
      of 92,747. The hydrophobicity plot of NHE-3 is very similar to that of NHE-1 and
      NHE-2. NHE-3 is also predicted to have 10-12 membrane-spanning domains and a long
      cytoplasmic domain which contains putative protein kinase phosphorylation motifs.
      NHE-3 exhibits overall 41% amino acid identity with NHE-1. NHE-3 is likely a
      glycoprotein as it has one potential N-linked glycosylation site, which is
      conserved in all NHEs identified. Northern blot analysis of poly(A+) RNA isolated
      from rabbit ileum using NHE-3 cDNA as a probe hybridized to a single 5.4-kilobase
      transcript. More detailed tissue distribution of message was performed by
      ribonuclease protection assay. It was found that NHE-3 message is only expressed
      in intestine and kidney, with the kidney cortex having the most abundant message,
      followed by intestine and kidney medulla. In intestine, ileum and ascending colon
      have the same amount of message, with much lesser amounts in jejunum. The message
      is absent from duodenum and descending colon, which lack the neutral NaCl
      absorptive process. Thus, NHE-3 might be involved in Na+ absorption in intestinal
      and renal epithelial cells.

PMID- 1374393
TI  - 3-Deazaadenosine inhibits thrombin-stimulated platelet-derived growth factor
      production and endothelial-leukocyte adhesion molecule-1-mediated monocytic cell
      adhesion in human aortic endothelial cells.
AB  - Injury to the vascular endothelium and the subsequent inflammatory response are
      considered prerequisites for the development of atherosclerosis. Platelet-derived
      growth factor (PDGF) production by and monocyte adhesion to aortic endothelial
      cells (EC) may participate in this inflammatory process and therefore are two
      potential targets for control by anti-inflammatory agents. Our previous studies
      have demonstrated that monocyte adhesion and PDGF production are stimulated by
      thrombin in EC. Here, we provide evidence that treatment of EC with the anti
      inflammatory agent 3-deazaadenosine (c3Ado) effectively abolished thrombin
      stimulated PDGF production and monocyte adhesion. c3Ado had no significant effect
      on either basal monocyte adhesion or constitutive PDGF production. c3Ado was also
      effective in negating monocyte adhesion induced by other agonists, such as
      interleukin-1, phorbol 12-myristate 13-acetate (PMA), and lipopolysaccharide.
      Northern analysis demonstrated that c3Ado significantly reduced thrombin- and PMA
      stimulated steady-state levels of PDGF-A chain, PDGF-B chain, and endothelial
      leukocyte adhesion molecule-1 (ELAM-1) mRNAs. Nuclear run-on studies demonstrated
      that a marked transcriptional activation of these genes by thrombin and PMA was
      abrogated by c3Ado treatment. The transcriptional rate of the alpha-tubulin gene
      was unaffected by the drug. Antibody binding studies with an anti-ELAM-1
      monoclonal antibody 7A9 revealed that thrombin-stimulated EC expression of ELAM-1
      was abolished by c3Ado, indicating that the suppression of ELAM-1 expression on
      EC surface may be a mechanism by which c3Ado interferes with monocyte adhesion.
      Experiments with the nucleoside transport inhibitor nitrobenzylthioinosine
      suggested that the transport of c3Ado into EC was required for its inhibitory
      activity. In addition, L-homocysteine thiolactone was found to potentiate the
      inhibitory activity of c3Ado, suggesting that the accumulation of intracellular
      c3Ado homocysteine may be the underlying mechanism by which c3Ado inhibits
      thrombin-induced EC function. Taken together, these results indicate that c3Ado
      may prove effective against vascular injury and inflammation through its ability
      to inhibit induction of both monocyte adhesion and PDGF production.

PMID- 1374394
TI  - Identification and functional characterization of protein kinase C isozymes in
      platelets and HEL cells.
AB  - To determine if selective activation of individual isozymes of protein kinase C
      (PKC) might explain the apparently divergent effects of PKC stimulation on
      platelets, we purified and characterized the isozymes from both platelets and
      human erythroleukemia (HEL) cells, a cell line that has many features of
      megakaryocytes. Two peaks of platelet PKC activity were resolved by
      hydroxylapatite chromatography; immunoblot analysis revealed that these two peaks
      represented the alpha and beta isozymes of PKC. In contrast, HEL cells produced
      only a single peak that contained the beta isozyme. None of the other PKC
      isozymes were detected in these fractions. The cytosol of platelets and HEL
      cells, however, were both found to contain the PKC-delta isozyme. Northern
      hybridization analyses and mRNA amplification by the polymerase chain reaction
      demonstrated the presence of mRNA encoding the alpha, beta, and delta PKC
      isozymes in platelets, but only the beta and delta isozymes in HEL cells. Phorbol
      myristate acetate (PMA), thrombin, or an endoperoxide analog induced the
      phosphorylation of the 47-kDa substrate of PKC (pleckstrin) found in platelets
      and HEL cells; preincubation of either HEL cells or platelets with PMA reduced
      the intracellular Ca2+ rise induced by thrombin. Thus, although both HEL cells
      and platelets contain PKC-beta and the recently described PKC-delta isozymes, the
      widely distributed alpha isozyme of PKC is absent in HEL cells; however, isozymes
      other than PKC-alpha are sufficient for some PMA-mediated functions that are
      similar to those seen in stimulated platelets.

PMID- 1374395
TI  - Cross-reactive immunodeterminants on Streptococcus sanguis and collagen.
      Predicting a structural motif of platelet-interactive domains.
AB  - Cross-reactive immunodeterminants on a fibril-associated surface antigen of
      Streptococcus sanguis and types I and III collagen participate in the induction
      of aggregation of human platelets. To further understand the basis for this
      apparent molecular mimicry, antitype-specific collagen antibodies, anti-KPGEPGPK
      (an analogue of platelet-interactive domains on collagen) and a panel of KPGEPGPK
      like synthetic peptides were used as probes. When collagen or S. sanguis cells
      were pretreated with the anti-collagen antisera, the induction of aggregation of
      platelet-rich plasma was greatly delayed or abrogated. These anti-collagen
      antibodies also neutralized KPGEPGPK and purified S. sanguis platelet-interactive
      antigens as inhibitors of S. sanguis or collagen-induced aggregation of platelets
      in plasma. In immunoblot analyses, these anti-collagen antibodies reacted with S.
      sanguis platelet-interactive antigens. Additionally, antisera against the
      platelet-interactive antigen of S. sanguis selectively reacted with undigested
      type I collagen and with fragments CB3 and CB6 of cyanogen bromide-treated type I
      collagen. Finally, when platelets were pretreated with synthetic peptides
      containing specific amino acid substitutions within the KPGEPGPK sequence, the
      time to onset of platelet-rich plasma aggregation by both agonists was altered.
      The hierarchical pattern of responses of platelets to these peptides and
      predictions of the structural changes produced by simulated insertions of each
      peptide into the CB4 sequence of type III collagen suggested conformational
      requirements for interactions with platelets. Thus, these data show that cross
      reactive immunodeterminants of S. sanguis and collagen induce platelet
      aggregation. The platelet-interactive domains are predicted to be characterized
      by a structural motif with the consensus sequence X-P-G-E-P/Q-G-P-X.

PMID- 1374396
TI  - Differential trans-activation of muscle-specific regulatory elements including
      the mysosin light chain box by chicken MyoD, myogenin, and MRF4.
AB  - We have isolated cDNAs encoding a chicken homologue of MRF4 (cMRF4) in addition
      to chicken MyoD (CMD1) and myogenin (c-myogenin) described previously. In an
      attempt to understand the roles that cMRF4, CMD1, and c-myogenin play in chicken
      myogenesis, the effects of these factors on muscle-specific cis-elements
      identified in regulatory regions of myosin alkali light chain (MLC) genes were
      examined. The promoter analysis of some of MLC genes has revealed two sorts of
      muscle-specific positive regulatory elements to date, an enhancer located
      upstream of the adult type LC1 gene and a cis-element, termed an MLC box,
      conserved among promoters of various MLC genes. The LC1 enhancer was exclusively
      trans-activated by CMD1. Although c-myogenin also activated transcription driven
      by the LC1 promoter, it was suggested that c-myogenin requires a cis-element(s)
      other than the CMD1-responsive enhancer. Chicken MRF4 could not trans-activate
      any of the constructs containing the LC1 promoter. In contrast, the promoter of
      the embryonic L23 gene was trans-activated by all of the three factors. From
      deletion and mutation analysis, the MLC box was shown to be involved in their
      positive regulation. These results extend previous observations that individual
      myogenic regulatory factors exhibit different capabilities in transcriptional
      activation of muscle-specific genes by acting distinctively upon their regulatory
      elements.

PMID- 1374397
TI  - Decrease in beta-subunit phosphotyrosine correlates with internalization and
      activation of the endosomal insulin receptor kinase.
AB  - In a previous study, we showed that the rat hepatic insulin receptor (IR) kinase
      of endosomes (ENs) was transiently activated to levels exceeding those of plasma
      membrane (PM) receptors following insulin injection. Phosphatase treatment of EN
      receptors abolished IR kinase activation implicating beta-subunit
      autophosphorylation as a mediator of the activation process (Khan, M. N.,
      Baquiran, G., Brule, C., Burgess, J., Foster, B., Bergeron, J. J. M., and Posner,
      B. I. (1989) J. Biol. Chem. 264, 12931-12940). In the present study, the
      phosphotyrosine (PY) content of the IR beta-subunit in PM and ENs was estimated
      by two different methods. In one method, direct in vivo labeling with 32Pi
      followed by receptor immunoprecipitation was carried out. In the second method,
      immunoblotting with antibodies against the submembrane domain of the IR beta
      subunit, encompassing residue 960 (alpha 960), and with antibodies against PY
      (alpha PY) was used to determine the content of PY/beta-subunit in PM and ENs
      following injection of insulin. By both methods, it was found that the PY content
      of PM IR was significantly greater than that of IR in ENs. With doses of 1.5
      micrograms of insulin/100 g body weight (50% receptor occupancy) or 15
      micrograms/100 g body weight (receptor saturation), the PY/beta-subunit of PM IR
      attained a level 2.0 to 2.5-fold of that observed for the IR of ENs.
      Surprisingly, the IR of ENs incorporated 3 to 5 times more PY/beta-subunit than
      those of PM consequent to autophosphorylation. Exogenous IR kinase activity
      (poly(Glu:Tyr)) in PM changed only slightly with insulin dose. In contrast, EN
      receptors exhibited a dose-dependent increase in kinase activity coincident with
      the decrease in PY/beta-subunit levels. A comparison of the proportion of
      receptor and kinase activity immunoprecipitated by alpha PY both before and after
      autophosphorylation indicated that ENs but not PM contained a small population of
      lightly phosphorylated but highly activated receptors. Since Thr12-Lys (IR kinase
      residues 1142-1153) efficiently inhibited IR autophosphorylation of both PM and
      EN receptors, Tris phosphorylation of beta-subunit regulatory tyrosines was
      unlikely. These results may be explicable by a dephosphorylation-dependent
      activation of IR kinase, as seen with the src family of tyrosine kinases.

PMID- 1374398
TI  - Characterization of an associated microfibril protein through recombinant DNA
      techniques.
AB  - The complete primary structure of a new extracellular protein associated with
      elastic fiber microfibrils was determined by recombinant DNA techniques.
      Antiserum to insoluble bovine ocular zonule protein was used to screen a lambda
      gt11 cDNA expression library constructed from whole chick embryo poly(A)+ RNA.
      The cDNAs encoding immunoreactive fusion polypeptides were then used to rescreen
      the library by plaque hybridization. Nucleotide sequencing of overlapping cDNA
      clones revealed an open translation reading frame of 1326 bases beginning at an
      initiation start sequence and ending at a stop codon. The contiguous cDNA
      sequence contains a 3'-untranslated region of 563 bases with a possible
      polyadenylation site 16 bases upstream from the poly(A) tail. Primer extension of
      chick aortic mRNA taken together with the sequence data, reveals a 5'
      untranslated region of 95 bases extending upstream from the translation start
      site. Northern blot analyses indicated that the isolated cDNA hybridized with a
      2.1-kilobase mRNA in preparations of whole chick embryo and chick embryonic
      aortic, heart, and muscle RNAs. The initial translation protein encoded by the
      cDNA is 53,932 kDa and possesses a hydrophilic amino acid composition with
      glutamic acid comprising 22% of the total amino acid residues. Antiserum was
      elicited to a synthetic peptide sequence (14 amino acids) encoded within the
      deduced protein primary structure. Western blots of extracted proteins from chick
      embryonic aortae cultured in the presence of beta-aminopropionitrile showed that
      the medium and a mild salt extract contained an immunoreactive protein possessing
      an apparent molecular mass of 58,000 whereas harsh denaturants extracted a 32,000
      kDa protein. Pulse-chase experiments using radiolabeled lysine showed that the
      newly synthesized 58,000-kDa protein was chased into a 32,000-kDa protein within
      a 2-24-h period. Immunoelectron microscopy of tissue sections from chick aortae,
      bovine nuchal ligament, and human ocular zonules showed that the peptide-elicited
      antibody localized specifically to ultrastructurally definable microfibril
      structures.

PMID- 1374399
TI  - Alterations in mRNA translation as a mechanism for the modification of enzyme
      synthesis during evolution. The ornithine decarboxylase model.
AB  - The expression of renal ornithine decarboxylase (ODC) is very different between
      the two murine species Mus domesticus and Mus pahari. The latter species contains
      a reduced level of ODC protein in the kidney, yet a normal concentration of ODC
      mRNA, indicating an alteration in translation, protein degradation, or both. We
      describe two lines of experimental evidence indicating that the efficiency of ODC
      mRNA translation is decreased in M. pahari. First, in vivo measurements showed
      that the rate of biosynthesis of the ODC polypeptide is reduced in M. pahari
      relative to M. domesticus. Second, polysome analyses indicated that, on average,
      the ODC mRNA of M. pahari binds fewer ribosomes. These effects, which are kidney
      specific, lend support to the notion that renal ODC expression in the two species
      differs at the level of mRNA translation. A full-length cDNA copy of the ODC mRNA
      of M. pahari was isolated, and its sequence was compared with that of M.
      domesticus. In the 5'-untranslated region, which is likely to play an important
      role in controlling translation, the M. pahari transcript contains several single
      base changes, as well as a 12-base deletion. These changes confer a distinct
      predicted secondary structure to this region of the mRNA and may be involved in
      reduced translation. We conclude that during evolution, modifications that alter
      the biosynthesis of specific proteins can occur at the translational level; these
      modifications exert their effects on translation in a transcript- and tissue
      specific manner.

PMID- 1374400
TI  - Regulation of the expression of pp160, a putative insulin receptor signal
      protein, by insulin, dexamethasone, and 1-methyl-3-isobutylxanthine in 3T3-L1
      adipocytes.
AB  - pp160, a cytosolic protein with Mr of approximately 160,000, is phosphorylated on
      tyrosine in response to insulin and is considered to be involved in signaling
      from the insulin receptor. The expression of pp160 during the differentiation of
      3T3-L1 fibroblasts to adipocytes and in adipocytes has been investigated using
      quantitative immunoblotting with antibodies against a peptide from pp160. Between
      day 6 and day 8 of differentiation induced by insulin, dexamethasone (Dex), and 1
      methyl-3-isobutylxanthine (Mix), pp160 expression increased 10-20-fold over the
      amount present in confluent fibroblasts. Omission of either insulin or Dex
      resulted in reduced expression of pp160 and in incomplete adipogenesis. Chronic
      treatment of fully differentiated adipocytes for 24 h with either insulin, Dex,
      or Mix alone in the presence of serum resulted in a decrease in the expression of
      pp160 by 70-85%. Chronic exposure to insulin caused a significant increase in the
      apparent size of pp160 to 172 kDa. Alkaline phosphatase treatment lowered the Mr
      of pp160 from both insulin-treated and basal cells to 150,000. These results
      demonstrate that pp160 is expressed in 3T3-L1 adipocytes during the time when
      insulin receptors are expressed in large numbers and that the maintenance of
      pp160 concentrations in adipocytes can be regulated by insulin, Mix, and Dex. The
      decreased expression of pp160 caused by these factors may be related to
      postreceptor insulin resistance.

PMID- 1374401
TI  - Receptor-mediated uptake and processing of vitamin D-binding protein in human B
      lymphoid cells.
AB  - Vitamin D-binding protein (DBP), a member of a multigene family including alpha
      fetoprotein (AFP) and albumin, is a serum glycoprotein that reversibly binds and
      transports vitamin D and its metabolites to target cells. In this work, we
      demonstrate that normal and malignant human B-lymphocytes specifically bind and
      internalize DBP. Radioiodinated DBP (125I-DBP) was used to follow the uptake of
      the protein by Raji cells, a human pre-B-lymphoma cell line. Time course studies
      of DBP uptake by these cells exhibited a saturable profile at both 4 and 37
      degrees C. The binding saturation curve obtained by incubating Raji cells at 4
      degrees C with different concentrations (1.5 nM to 1.5 microM) of 125I-DBP showed
      two saturation plateaus; Scatchard analysis showed the presence of two groups of
      receptor sites with a Kd1 of 2.04 x 10(-7) M (n1 = 42,161 +/- 4,336 sites/cell)
      and a Kd2 of 1.01 x 10(-6) M (n2 = 198,000 +/- 48,000 sites/cell). After
      incubation of Raji cells at 37 degrees C with both fluorescein isothiocyanate
      (FITC) and horseradish peroxidase conjugates, DBP was internalized and could be
      localized in the cytoplasm. DBP-horseradish peroxidase conjugates were used to
      follow the uptake and to determine the endocytic pathway of the protein in Raji
      cells. The initial steps, contrary to those observed for AFP, did not apparently
      involve coated pits and vesicles. Small vesicles (approximately 50-60 nm) with
      electron-dense DBP-horseradish peroxidase reaction products were observed that
      could fuse with large endosomes. These endosomes appeared dispersed in the
      cytoplasm with some preferential localization in the Golgi centrosphere region.
      Pulse-chase experiments showed that only 10% of the uptaken protein was released
      in a nondegraded form. Accordingly, most DBP molecules accumulated in endosomes
      should be degraded in lysosomes, instead of being recycled back to the surface,
      as in the case of AFP. Contrary to malignant B-cells (Raji), the uptake ability
      for DBP of normal quiescent B-lymphocytes was very low. Specific binding and
      internalization of DBP-FITC by these cells were observed following mitogen
      induced activation. Significant values of uptake were obtained at 37 degrees C
      after 72 h of incubation in the presence of pokeweed mitogen. The binding of DBP
      FITC was partially inhibited in the presence of an excess of unlabeled protein.
      Taken together, the actual results suggest that DBP receptors are constitutively
      expressed by malignant B-cells and in a transitory form by normal B-lymphocytes
      undergoing mitogen-induced activation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374402
TI  - Cloning and expression of a novel angiotensin II receptor subtype.
AB  - Angiotensin II (AII) is a major regulator of cardiovascular function and fluid
      homeostasis. Recently, the cDNA for an AII receptor (AT1) was cloned from rat
      smooth muscle and bovine adrenal. To search for AII receptor subtypes, we
      amplified rat adrenal cortex cDNA by PCR using primers based on the AT1 receptor.
      The product was distinct from the AT1 receptor as indicated by restriction enzyme
      analysis and DNA sequencing. A full-length cDNA clone (2.2 kilobase pairs)
      encoding a novel AII receptor (AT3) was obtained by screening an adrenal cortex
      library. The AT3 cDNA encodes a Mr 40,959 protein with 95% amino acid identity to
      the rat smooth muscle receptor, but the overall nucleotide similarity is 71% due
      to low homology in the 5'- (58%) and 3'- (62%) untranslated regions. Expressed
      AT3 receptors in Xenopus oocytes and COS-7 cells mediate agonist-induced Ca2+
      mobilization but are pharmacologically distinct from the AT1 receptors. AT3 mRNA
      is most abundant in the adrenal cortex and pituitary and differs from AT1 mRNA in
      its tissue distribution. The structural features of the AT3 receptor, including
      two additional potential phosphorylation sites for protein kinase C, could be
      related to the distinctive binding properties of the adrenal and vascular
      receptors and to their differential regulation during altered sodium intake.

PMID- 1374403
TI  - Cyclic AMP-dependent protein kinase activation of cystic fibrosis transmembrane
      conductance regulator chloride channels in planar lipid bilayers.
AB  - Membrane vesicles, prepared from mouse NIH-3T3 fibroblasts and Chinese hamster
      ovary cells expressing high levels of cystic fibrosis transmembrane conductance
      regulator (CFTR), were fused with Mueller-Rudin planar lipid bilayers. Upon
      addition of the catalytic subunit of cAMP-dependent protein kinase and ATP, low
      conductance Cl(-)-selective ion channels were observed in 10 of 16 experiments.
      The channels had a linear current-voltage relationship and a unitary conductance
      of approximately 6.5 pS. The channels were more permeable to Cl- than to I- and
      showed no appreciable time-dependent voltage activation. In contrast, addition of
      cAMP-dependent protein kinase and ATP to lipid bilayers fused with vesicles
      prepared from mock transfected (n = 14) cells failed to activate Cl- channels.
      These data support the conclusion that CFTR is a Cl- channel. They indicate that
      it can be reconstituted in a planar lipid bilayer and that the biophysical and
      regulatory properties are very similar to those observed in the native cell
      membrane. These data also argue against the requirement for loosely associated
      factors for regulation or function of the channel.

PMID- 1374404
TI  - FK506 binding protein associated with the calcium release channel (ryanodine
      receptor).
AB  - The calcium release channel (CRC)/ryanodine receptor (RyRec) has been identified
      as the foot structure of the sarcoplasmic reticulum (SR) and provides the pathway
      for calcium efflux required for excitation-contraction coupling in skeletal
      muscle. The CRC has previously been reported to consist of four identical 565-kDa
      protomers. We now report the identification of a 12-kDa protein which is tightly
      associated with highly purified RyRec from rabbit skeletal muscle SR. N-terminal
      amino acid sequencing and cDNA cloning demonstrates that the 12-kDa protein from
      fast twitch skeletal muscle is the binding protein for the immunosuppressant drug
      FK506. In humans, FK506 binds to the 12-kDa FK506-binding protein (FKBP12) and
      blocks calcium-dependent T cell activation. We find that FKBP12 and the RyRec are
      tightly associated in skeletal muscle SR on the basis of: 1) co-purification
      through sequential heparin-agarose, hydroxylapatite, and size exclusion
      chromatography columns; 2) coimmunoprecipitation of the RyRec and FKBP12 with
      anti-FKBP12 antibodies; and 3) subcellular localization of both proteins to the
      terminal cisternae of the SR, and not in the longitudinal tubules of SR, in fast
      twitch skeletal muscle. The molar ratio of FKBP12 to RyRec in highly purified
      RyRec preparations is approximately 1:4, indicating that one FKBP12 molecule is
      associated with each calcium release channel/foot structure.

PMID- 1374405
TI  - Localization of the protein 4.1-binding site on the cytoplasmic domain of
      erythrocyte membrane band 3.
AB  - Of the several proteins that bind along the cytoplasmic domain of erythrocyte
      membrane band 3, only the sites of interaction of proteins 4.1 and 4.2 remain to
      be at least partially localized. Using five independent techniques, we have
      undertaken to map and characterize the binding site of band 4.1 on band 3. First,
      transfer of a radioactive cross-linker (125I-2-(p-azido-salicylamido)ethyl-1-3
      dithiopropionate) from purified band 4.1 to its binding sites on stripped inside
      out erythrocyte membrane vesicles (stripped IOVs) revealed major labeling of band
      3, glycophorin C, and glycophorin A. Proteolytic mapping of the stripped IOVs
      then demonstrated that the label on band 3 was confined largely to a fragment
      comprising residues 1-201. Second, competitive binding experiments with Fab
      fragments of monoclonal and peptide-specific polyclonal antibodies to numerous
      epitopes along the cytoplasmic domain of band 3 displayed stoichiometric
      competition only with Fabs to epitopes between residues 1 and 91 of band 3. Weak
      competition was also observed with Fabs to a sequence of the cytoplasmic domain
      directly adjacent to the membrane-spanning domain, but only at 50-100-fold excess
      of Fab. Third, band 4.1 protected band 3 from chymotryptic hydrolysis at tyrosine
      46 and to a much lesser extent at a site within the junctional peptide connecting
      the membrane-spanning and cytoplasmic domains of band 3. Fourth, ankyrin, which
      has been previously shown to interact with band 3 both near a putative central
      hinge and at the N terminus competed with band 4.1 for band 3 in stripped IOVs.
      Since band 4.1 does not associate with band 3 near the flexible central hinge,
      the competition with ankyrin can be assumed to derive from a mutual association
      with the N terminus. Finally, a synthetic peptide corresponding to residues 1-15
      of band 3 was found to mildly inhibit band 4.1 binding to stripped IOVs. Taken
      together, these data suggest that band 4.1 binds band 3 predominantly near the N
      terminus, with a possible secondary site near the junction of the cytoplasmic
      domain and the membrane.

PMID- 1374406
TI  - Cloning and nucleotide sequence of the gene (citC) encoding a citrate carrier
      from several Salmonella serovars.
AB  - The nucleotide sequence of the citC coding for the citrate carrier in several
      Salmonella serovars has been determined, and the amino acid sequence of the
      carrier protein was deduced. The predicted citrate carrier from Salmonella
      pullorum and Salmonella enteritidis consists of 446 amino acids with a molecular
      weight of 47,621, whereas that from Salmonella dublin is the same 446 amino acids
      with the slightly different molecular weight of 47,591, because 1 amino acid
      residue was substituted. The predicted proteins are highly hydrophobic (69%
      nonpolar amino acids). The hydropathy profile suggests that the proteins are
      composed of 11-12 hydrophobic membrane-spanning segments with two hydrophilic
      cores in the middle of the protein sequence. No homology in the nucleotide and
      amino acid sequences was found in the molecular structures of citA, citP, and
      tctI genes. The citC-coding citrate transport activity is Na(+)-dependent and
      specific for citrate only. The transcript from the citC gene was not detected in
      the total RNA from several Salmonella serovars except S. dublin in Northern blot
      analysis, although the promoter of the citC genes appeared to be functional in
      Escherichia coli and Salmonella typhimurium strains using the lacZ fusion assay.
      These results suggested that the citC gene-coding citrate carrier is probably a
      TctIII system such as that identified previously in S. typhimurium.

PMID- 1374407
TI  - Role of sequences within the first intron in the regulation of expression of
      eukaryotic initiation factor 2 alpha.
AB  - Resting human peripheral blood T cells synthesize proteins at very low rates and
      contain very low levels of eukaryotic initiation factor (eIF) 2 alpha mRNA.
      During mitogenic activation, the level of eIF-2 alpha mRNA increases at least 50
      fold, an effect thought to be due primarily to intranuclear stabilization of the
      primary transcript (Cohen, R. B., Boal, T. R., and Safer, B. (1990) EMBO J. 9,
      3831-3837). Analysis of sequences within the first intron revealed a region with
      homology to the "initiator" (Inr) sequence first described by Smale and Baltimore
      (Smale, S. T., and Baltimore, D. (1989) Cell 57, 103-113). This Inr element is
      positioned 450 bases downstream of the eIF-2 alpha promoter and is oriented to
      generate an overlapping antisense transcript. Deletion or mutation of the Inr
      element results in a reproducible 5-8-fold increase in the activity of an eIF-2
      alpha promoter-driven CAT reporter gene and a corresponding 2.5-fold decrease in
      activity of an antisense driven luciferase reporter gene in vivo in 293 cells. In
      vitro transcription analysis also reveals antisense transcripts which depend on
      an intact Inr element and whose 5' ends map to sequences surrounding the Inr
      consensus sequence. A potential role for double-stranded RNA generated by these
      overlapping divergent transcription units in the regulation of eIF-2 alpha gene
      expression in T cells is suggested.

PMID- 1374408
TI  - The N terminus of human myelin basic protein consists of C2, C4, C6, and C8 alkyl
      carboxylic acids.
AB  - Peptide 1-21, generated by cyanogen bromide cleavage of each of two highly
      purified components of human myelin basic protein, components 1 and 8, gave a
      series of peaks in the fast atom bombardment mass spectra with m/z 2299, 2327,
      2355, 2383, and 2411, indicating additions of 42, 70, 98, 126, and 154 atomic
      mass units respectively with m/z 2327 and 2355 as the dominant species. The
      pentafluorobenzyl esters prepared from an acid hydrolysate analyzed by negative
      ion chemical ionization gas chromatography mass spectrometry confirmed that C6,
      C8, and C10 fatty acids were present. These data demonstrated (i) that the N
      terminus of a myelin basic protein is not simply acetylated but contains C2, C4,
      C6, C8, and C10 fatty acids with C4 and C6 as the dominant species, (ii) the two
      components studied (C-1 and C-8) showed different relative amounts of C2 and C8
      in particular, and (iii) human myelin basic protein is the first protein to be
      reported with a complex N terminus consisting of several alkyl carboxylic acid
      species.

PMID- 1374409
TI  - The high molecular weight Cat-301 chondroitin sulfate proteoglycan from brain is
      related to the large aggregating proteoglycan from cartilage, aggrecan.
AB  - Monoclonal antibodies Cat-301 and Cat-304 recognize a neuronal cell surface
      associated chondroitin sulfate proteoglycan (CSPG), which is expressed during
      critical periods of postnatal development in the mammalian central nervous system
      (CNS). In the present study we show that the CNS CSPG identified by Cat-301/304
      is similar to aggrecan, the high molecular weight CSPG from cartilage. By Western
      blot analysis, cartilaginous tissues, which are rich sources of aggrecan, have a
      high concentration of a high molecular weight CSPG which is immunoreactive with
      Cat-301 and 304. The Cat-301 and 304 epitopes, however, are partially masked by
      chondroitin sulfate glycosamino-glycan and are unmasked by digestion of the
      antigen with chondroitinase ABC. Although the antigen from both cartilage and CNS
      can be purified by CsCl buoyant density gradient centrifugation, a standard
      technique for purifying aggrecan, most of the antigen from the CNS has a lower
      buoyant density than that of cartilage. This may be due, in part, to the paucity
      of keratan sulfate substitution on the CNS antigen compared with that of the
      cartilage antigen. Both the CNS and cartilage antigens bind to hyaluronic acid, a
      feature characteristic of aggrecan. The physiochemical, biochemical, and
      functional properties of the Cat-301/304 antigen from cartilage are identical to
      aggrecan. The CNS antigen is similar, but not identical, to the cartilage
      antigen, and may thus represent another member of the family of high molecular
      weight CSPGs which bind to and aggregate with hyaluronic acid.

PMID- 1374410
TI  - Immunohistochemical demonstration of proliferating cell nuclear antigen in
      glioblastomas: pronounced heterogeneity and lack of prognostic significance.
AB  - In order to evaluate a possible significance of the expression of proliferating
      cell nuclear antigen (PCNA) as clinically useful prognostic parameter, we
      retrospectively investigated a series of 40 glioblastomas by means of
      immunohistochemistry and compared the results to patient survival. All
      glioblastomas included in the study had been treated by operation, radiotherapy
      and intraarterial ACNU [3-(4-amino-2-methyl-5-pyrimidinylmethyl)-1-(2
      chloroethyl)-1-nitr osourea] chemotherapy. Patient survival ranged from 2 months
      to 42 months (mean: 14.2 months). PCNA values varied widely, ranging from 0.5% to
      75% (mean: 24.9%). Statistical analysis revealed no significant correlation
      between PCNA index and patient survival. Our study thus indicates that the
      expression of PCNA appears not to be a useful prognostic parameter for
      glioblastoma patients.

PMID- 1374411
TI  - MACOP-B treatment in patients with Ki-1-positive large-cell anaplastic lymphoma.
AB  - Nine adult patients with Ki-1-positive large-cell anaplastic lymphoma were
      treated with MACOP-B. Two suffered from relapsed disease and had previously
      received chemotherapy; a third patient had received a single dose of 100 mg/m2
      cisplatin before initiation of MACOP-B. The stage of lymphoma was determined
      according to the Ann Arbor Conference criteria and was II in one, III in two and
      IV in six patients. All patients had constitutional symptoms. Five patients had
      achieved complete remission 4 weeks after termination of the protocol and there
      were two partial remissions. One patient died of massive pulmonary embolism
      during the 4th week of treatment; another patient, who had received MACOP-B as
      salvage therapy, died of progressive lymphoma 1 month after completion of the
      regimen. Maximal observed toxicities according to WHO were mucositis grade 3 (n =
      3) and there were three cases with thromboembolic complications, including a
      fatal pulmonary embolism in a young patient. However, MACOP-B appears an
      effective, fairly well-tolerated and feasible therapy for patients with Ki-1
      positive large-cell anaplastic lymphoma.

PMID- 1374412
TI  - Comparative analysis of CA72-4, CA195 and carcinoembryonic antigen in patients
      with gastrointestinal malignancies.
AB  - To establish further the clinical significance of the novel quantitative
      immunoradiometric assay system CA72-4 in patients with gastric and other
      digestive tract malignancies, the sera of a total of 208 subjects have been
      analysed and levels of carcinoembryonic antigen (CEA) and another promising new
      tumour marker, CA195, have been compared. Twenty patients had gastric (GC), 60
      colorectal (CC), and 14 pancreatic carcinomas (CC); 94 patients had benign
      disorders, and 20 were healthy volunteers. CA72-4 elevations above normal
      (greater than 4 U/ml) were observed in 6 (30%) GC, 17 (28%) CC, and 8 (57%) PC
      patients. CA195 appeared more sensitive and was increased (greater than 10 U/ml)
      in 35% GC, 70% CC, and in 100% PC patients; CEA levels above normal (greater than
      5 ng/ml) were noted in 35%, 45%, and 66% of patients respectively. CA72-4 had a
      rather high specificity and was increased in only 6/94 (6%) patients with benign
      diseases, whereas CA195 had a false positive rate of 23%, and CEA of 33%. Among
      20 healthy donors, none had elevated levels of CA72-4 or CA195, but marginal
      elevations of CEA were noted in 3 smokers. Despite some advantage of the new
      tumour marker CA72-4 in terms of specificity, its value as a serodiagnostic test
      in gastrointestinal cancer patients seems inferior to that of CA195 and CEA.

PMID- 1374414
TI  - Specific association of the proto-oncogene product pp60c-src with an
      intracellular organelle, the PC12 synaptic vesicle.
AB  - The protein product of the proto-oncogene c-src is a membrane-associated tyrosine
      kinase of unknown function. Identification of pp60c-src target membranes may
      elucidate the function of the c-src protein. The available evidence indicates
      that pp60c-src associates with distinct membranes within single cell types and
      has different distributions in different cell types. Our experiments demonstrate
      targeting of pp60c-src to an isolatable and biochemically identified membrane
      fraction in the neuroendocrine cell line PC12. The c-src protein was found to be
      specifically associated with synaptic vesicles since: (a) the pp60c-src
      immunofluorescent pattern overlapped with a synaptic vesicle marker,
      synaptophysin; (b) a significant proportion (44%) of the pp60c-src from PC12 but
      not fibroblast postnuclear supernatants was recovered in a small vesicle
      fraction; (c) an anti-synaptophysin cytoplasmic domain antibody immunodepleted
      all of the pp60c-src vesicles in this fraction, and (d) pp60c-src copurified
      during a 100-fold purification of PC12 synaptic vesicles. These results suggest a
      role for the c-src protein in the regulation of synaptic vesicle function.

PMID- 1374413
TI  - The three members of the selectin receptor family recognize a common carbohydrate
      epitope, the sialyl Lewis(x) oligosaccharide.
AB  - The selectins (lectin-EGF-complement binding-cell adhesion molecules [LEC-CAMs])
      are a family of mammalian receptors implicated in the initial interactions
      between leukocytes and vascular endothelia, leading to lymphocyte homing,
      platelet binding, and neutrophil extravasation. The three known selectins, L
      selectin (leukocyte adhesion molecule-1 [LECAM-1]), E-selectin (endothelial
      leukocyte adhesion molecule-1 [ELAM-1]), and P-selectin (GMP-140) share
      structural features that include a calcium-dependent lectin domain. The sialyl
      Lewis(x) carbohydrate epitope has been reported as a ligand for both E- and P
      selectins. Although L-selectin has been demonstrated to bind to carbohydrates,
      structural features of potential mammalian carbohydrate ligand(s) have not been
      well defined. Using an ELISA developed with a sialyl Lewis(x)-containing
      glycolipid and an E-selectin-IgG chimera, we have demonstrated the direct binding
      of the L-selectin-IgG chimera to sialyl Lewis(x). This recognition was calcium
      dependent, and could be blocked by Mel-14 antibody but not by other antibodies.
      Recognition was confirmed by the ability of cells expressing the native L
      selectin to adhere to immobilized sialyl Lewis(x). These data suggest that the
      sialyl Lewis(x) oligosaccharide may form the basis of a recognition domain common
      to all three selectins.

PMID- 1374415
TI  - Requirement of the integrin beta 3 subunit for carcinoma cell spreading or
      migration on vitronectin and fibrinogen.
AB  - FG human pancreatic carcinoma cells use integrin alpha v beta 5 as their primary
      vitronectin receptor since they fail to express integrin alpha v beta 3. These
      cells are unable to form focal contacts, spread, or migrate on vitronectin but
      readily do so on collagen in a beta 1 integrin-dependent manner. Transfection of
      FG cells with a cDNA encoding the integrin beta 3 subunit results in the surface
      expression of a functional integrin alpha v beta 3 heterodimer providing these
      cells with novel adhesive and biological properties. Specifically, FG cells
      expressing beta 3 acquire the capacity to attach and spread on vitronectin as
      well as fibrinogen with beta 3 localization to focal contacts. Moreover, these
      cells gain the capacity to migrate through a porous membrane in response to
      either vitronectin or fibrinogen. These results demonstrate that the beta 3 and
      beta 5 integrin subunits when associated with alpha v, promote distinct cellular
      responses to a vitronectin extracellular environment.

PMID- 1374416
TI  - Regulation of alpha 2 beta 1-mediated fibroblast migration on type I collagen by
      shifts in the concentrations of extracellular Mg2+ and Ca2+.
AB  - Extracellular Ca2+ can reverse the Mg(2+)-dependent, alpha 2 beta 1-mediated
      adhesion of WI38 human fibroblasts to type I collagen substrates. Affinity
      chromatography data also demonstrate that Ca2+ can specifically elute the
      fibroblast alpha 2 beta 1 integrin bound to type I collagen-Sepharose in Mg2+. In
      modified Boyden chamber migration assays, Mg2+ alone supports the alpha 2 beta 1
      mediated migration of fibroblasts on type I collagen substrates, while Ca2+ does
      not. However, a twofold enhancement in migration was observed when combinations
      of the two cations were used, with optimal migration observed when the Mg2+/Ca2+
      ratio was higher than one. Inhibitory mAbs directed against various integrin
      subunits demonstrate that these observed cation effects appear to be mediated
      primarily by alpha 2 beta 1. These data, together with reports that under certain
      physiological conditions significant fluctuations in the concentrations of
      extracellular Ca2+ and Mg2+ can take place in vivo, suggest that the ratio
      between these two cations is involved in the up- and downregulation of integrin
      function, and thus, may influence cell migratory behavior.

PMID- 1374418
TI  - Development of low- and high-functioning autistic children.
AB  - Aspects of developmental sequences and structures were assessed in low- and high
      functioning autistic and non-autistic developmentally disabled children. Specific
      developmental issues examined included sequences, regressions and profiles.
      Classification into the high- or low-functioning groups was based on a full scale
      IQ cutoff of 50. In general, there were few differences in the sequences of
      development among the groups. However, the autistic children were more likely
      than non-autistic children to display developmental regressions and unevenness
      across developmental domains. These developmental peculiarities were more
      pronounced in the low- as compared to high-functioning autistic children. These
      findings are discussed with regard to issues of developmental processes,
      classification and autism.

PMID- 1374419
TI  - Debate and argument: clarifying developmental issues in the study of autism.

PMID- 1374417
TI  - Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3
      methylglutaryl coenzyme A reductase: implications for enzyme degradation in the
      endoplasmic reticulum.
AB  - We have raised two monospecific antibodies against synthetic peptides derived
      from the membrane domain of the ER glycoprotein 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase, the rate limiting enzyme in the cholesterol
      biosynthetic pathway. This domain, which was proposed to span the ER membrane
      seven times (Liscum, L., J. Finer-Moore, R. M. Stroud, K. L. Luskey, M. S. Brown,
      and J. L. Goldstein. 1985. J. Biol. Chem. 260:522-538), plays a critical role in
      the regulated degradation of the enzyme in the ER in response to sterols. The
      antibodies stain the ER of cells and immunoprecipitate HMG-CoA reductase and
      HMGal, a chimeric protein composed of the membrane domain of the reductase fused
      to Escherichia coli beta-galactosidase, the degradation of which is also
      accelerated by sterols. We show that the sequence Arg224 through Leu242 of HMG
      CoA reductase (peptide G) faces the cytoplasm both in cultured cells and in rat
      liver, whereas the sequence Thr284 through Glu302 (peptide H) faces the lumen of
      the ER. This indicates that a sequence between peptide G and peptide H spans the
      membrane of the ER. Moreover, by epitope tagging with peptide H, we show that the
      loop segment connecting membrane spans 3 and 4 is sequestered in the lumen of the
      ER. These results demonstrate that the membrane domain of HMG-CoA reductase spans
      the ER eight times and are inconsistent with the seven membrane spans topological
      model. The approximate boundaries of the proposed additional transmembrane
      segment are between Lys248 and Asp276. Replacement of this 7th span in HMGal with
      the first transmembrane helix of bacteriorhodopsin abolishes the sterol-enhanced
      degradation of the protein, indicating its role in the regulated turnover of HMG
      CoA reductase within the endoplasmic reticulum.

PMID- 1374420
TI  - Debate and argument: on modularity and development in autism: a reply to Burack.
AB  - Burack (this issue) reopens questions first raised by my 1989a article in this
      Journal, on whether children with autism have a specific delay in the development
      of a theory of mind, or whether the data reflect deviance rather than delay. His
      paper is of considerable value in highlighting points for debate. In my response,
      I focus on three issues: First, the logical possibility that delay and deviance
      can occur together. Second, the evidence that autism may instantiate this
      possibility. Finally, the important question of the modularity of theory of mind.

PMID- 1374421
TI  - High-performance liquid chromatography of histamine and 1-methylhistamine with on
      column fluorescence derivatization.
AB  - An on-column fluorometric derivatization method was developed for the
      determination of histamine and 1-methylhistamine (HMs) by high-performance liquid
      chromatography. The system for the derivatization consisted only of a
      commercially available single-plunger pump and a reversed-phase C18 column
      supported on synthetic polymer with a mobile phase of acetonitrile and alkaline
      borate buffer solution containing o-phthalaldehyde as a derivatization reagent.
      It required no additional reaction system as for a post-column derivatization
      method. Injected HMs might be derivatized to a fluorophore on the inlet site of
      the high-performance liquid chromatographic column, followed by chromatography on
      the same column. Optimization of the on-column reaction conditions resulted in a
      simple and sensitive analytical method for the determination of HMs with
      excellent reproducibility and linearity of 0.05-5 micrograms/ml of both HMs.
      Application of this method to the determination of HMs in food samples resulted
      in a limit of quantification of 0.05 mg/100 g and in a greater than 95% overall
      mean recovery at a fortification of 0.1 mg/g of both HMs. This method was
      furthermore applicable to the determination of histamine released from rat
      peritoneal mast cells.

PMID- 1374422
TI  - Frequency of T cells specific for myelin basic protein and myelin proteolipid
      protein in blood and cerebrospinal fluid in multiple sclerosis.
AB  - T cell sensitization to two myelin components, myelin basic protein (MBP) and
      myelin proteolipid protein (PLP), may be important to the pathogenesis of
      multiple sclerosis (MS). Using the limiting dilution assay, we demonstrated that
      the blood of MS patients had an increased frequency of MBP-reactive T cells
      compared with normal subjects and patients with other neurological diseases (OND)
      and rheumatoid arthritis. There was no difference in T cell frequency to a
      synthetic peptide, PLP139-151, or Herpes simplex virus. Within cerebrospinal
      fluid (CSF), 37% of IL-2/IL-4-reactive T cell isolates from MS patients responded
      either to MBP or PLP139-151 while only 5% of similar isolates from OND patients
      responded to these myelin antigens. The mean relative frequency of MBP-reactive T
      cells within CSF from MS patients was significantly higher than that of OND
      patients (22 x 10(-5) cells versus 1 x 10(-5) cells) and was similar to that of
      MBP reactive T cells within the central nervous system of rats with experimental
      autoimmune encephalomyelitis. These results lend new support to the hypothesis
      that myelin-reactive T cells mediate disease in MS.

PMID- 1374423
TI  - Epitope mapping of polyclonal and monoclonal antibodies against two alpha
      bungarotoxin-binding alpha subunits from neuronal nicotinic receptors.
AB  - Recently, cDNAs for alpha subunits of two different neuronal alpha-bungarotoxin
      binding proteins (alpha BgtBP) were isolated from chick brain, designated alpha
      BgtBP alpha 1 and alpha BgtBP alpha 2. These are now also referred to as subunits
      alpha 7 and alpha 8, respectively. Expression studies in Xenopus oocytes have
      indicated that alpha 7 subunits are able to form cation channels that are
      sensitive to nicotinic ligands, and therefore represent bona fide nicotinic
      acetylcholine receptor subunits. Polyclonal and monoclonal antibodies (mAbs) have
      been produced against: (i) affinity-purified chick brain alpha BgtBP; and (ii)
      fusion proteins containing the unique cytoplasmic sequences alpha 7(327-412) and
      alpha 8(293-435). Here, synthetic overlapping peptides corresponding to their
      deduced amino acid sequences are used to map the epitopes recognized by the
      different antibodies. The polyclonal response to affinity-purified alpha BgtBPs
      and the fusion proteins indicates that sequence segments 290-420 of both subunits
      contain several major and minor epitopes. mAbs selected for their ability to bind
      both native and denatured alpha BgtBPs isolated from chick brain also recognize
      subunit-specific sequential epitopes within the sequence segment 290-420. The
      epitopes recognized by the mAbs correspond to the minor epitopes defined using
      antisera. The mAbs characterized in these studies will provide useful probes for
      further studies of alpha BgtBP structure and histological localization.

PMID- 1374424
TI  - Immune processing of proteolipid protein by subsets of antigen-presenting spleen
      cells.
AB  - Myelin proteolipid protein (PLP) contains one established antigenic epitope
      within the 139-151 amino acid sequence, with encephalitogenic activity for SJL
      mice (PLP139-151). In the current study, the processing and presentation of PLP
      by subsets of splenic antigen-presenting cells (APC) were examined by comparing
      their capacity to stimulate PLP-responsive T-cell clones, two of which are
      specific for PLP139-151, and one which is not specific for this peptide. In order
      to study whether PLP requires processing before its presentation by APC, PLP
      pulsed and fixed APC were shown to stimulate PLP-specific T cells. However, the
      addition of PLP to unpulsed, fixed APC resulted in the absence of T-cell
      stimulation, while the ability of these fixed APC to bind antigenic peptide and
      efficiently present it to T cells, was demonstrated by their ability to use a
      synthetic peptide for the stimulation of the T cells. In order to study
      potentially different processing efficiencies among APC subsets, spleen cells
      were fractionated by adherence to plastic, and their respective APC activities
      were studied separately. The non-adherent (NAd) APC were unable to stimulate
      PLP139-151 specific T-cell clones with PLP as antigen. In contrast, a T-cell
      clone specific for a separate, but unidentified epitope on PLP was stimulated by
      NAd APC efficiently. In addition, stimulation of PLP139-151-specific T-cell
      clones by NAd APC did occur when the synthetic peptide instead of intact PLP was
      used as antigen, indicating a defect in PLP processing by the NAd APC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1374425
TI  - Virus-reactive and autoreactive T cells are accumulated in cerebrospinal fluid in
      multiple sclerosis.
AB  - Elevated numbers of B cells--plasma cells secreting antibodies to measles and
      mumps virus, and to myelin associated glycoprotein (MAG), one of several putative
      myelin autoantigens--have previously been reported in cerebrospinal fluid (CSF)
      from patients with multiple sclerosis (MS), while it is unknown if corresponding
      T cell reactivities occur. We have defined the T cell reactivities to measles and
      mumps virus and to MAG in an immunospot assay which is based on the detection of
      secretion of interferon-gamma (IFN-gamma) by single cells upon stimulation with
      specific antigen in short term cultures. Patients with MS had higher numbers of
      MAG-reactive T cells in blood compared to controls, while no differences were
      observed for measles or mumps virus-reactive T cells. In CSF, elevated numbers of
      MAG-reactive T cells and also of measles- and mumps-reactive T cells were found
      in patients with MS compared to other neurological diseases. A strong
      accumulation of antigen-reactive T cells was observed in the MS patients' CSF
      compared to blood. The magnitude of these T cell reactivities did not correlate
      with clinical MS variables. The T cell repertoire in MS thus includes, besides
      myelin basic protein, proteolipid protein and myelin oligodendrocyte
      glycoprotein, also MAG and, in addition, measles and mumps virus. It is not clear
      whether these T cell reactivities accumulated in the CSF have importance for the
      pathogenesis of MS or reflect phenomena secondary to myelin damage, or result
      from both these alternatives.

PMID- 1374426
TI  - Tolerance to acetylcholine receptor induced by AChR-coupled syngeneic cells.
AB  - Intravenous administration of acetylcholine receptor (AChR)-coupled syngeneic
      spleen cells induced AChR-specific tolerance in Lewis rats. Injection of 20 x
      10(6) AChR-coupled spleen cells resulted in a significant reduction of the
      antibody response to AChR when the animals were subsequently immunized with AChR
      (up to 66% inhibition). Tolerance induced by AChR-coupled cells was antigen
      specific: challenge with AChR plus an unrelated antigen, ovalbumin (OVA),
      resulted in significantly reduced serum antibody titers to AChR but normal or
      enhanced titers to OVA, compared to controls. Lymphocytes from these rats showed
      substantially reduced proliferative responses in vitro to AChR, and normal or
      enhanced responses to OVA. To investigate the role of Ia antigens in tolerance
      induction, AChR was coupled to Ia-positive or Ia-negative spleen cells. Injection
      of AChR-coupled Ia-positive cells induced antigen-specific tolerance to AChR;
      challenge with AChR plus OVA resulted in reduced serum antibody titers and
      lymphoproliferative responses to AChR, and normal or enhanced titers and cellular
      responses to OVA. Injection of AChR-coupled Ia-negative cells did not induce
      tolerance to AChR. These results demonstrate that AChR, which is known to be
      highly immunogenic, can be rendered tolerogenic without denaturation or linkage
      to toxic substances. The possible mechanisms of tolerance induced by AChR-coupled
      spleen cells are discussed.

PMID- 1374427
TI  - Effects of insulin-like growth factors and growth hormone on the in vitro
      proliferation of T lymphocytes.
AB  - The insulin-like growth factors I and II (IGF-I and IGF-II) promote proliferation
      and differentiation of many cell types. We report that recombinant IGF-I and IGF
      II augment both the lectin- and anti-CD3-induced proliferation of human
      peripheral blood mononuclear cells (PBMC) at concentrations proportional to their
      binding affinities. IGF-I and IGF-II also augmented the lectin-induced
      proliferation of purified T lymphocytes. Effects of IGF-I were found in cultures
      of T cells vigorously depleted for monocytes and supplemented with saturating
      concentrations of interleukin-1. The latter results indicate that the effect of
      IGF-I on the proliferation of T lymphocytes can occur independent of monocytes or
      monocyte-derived factors.

PMID- 1374428
TI  - Parents' developmental perceptions and expectations for their high-risk infants.
AB  - This study examines the relationship between developmental outcomes of high-risk
      infants and parental perceptions and expectations. Parents of 209 consecutive
      high-risk infants were asked to provide their development interpretations and
      expectations before their infants received standard developmental assessments
      between April and October 1989. Moderate correlations between parents and
      professional assessments of motor and language skills were noted (p less than .05
      to p less than .01). Most agreements occurred when infants were assessed as
      normal by professionals. Disagreements were common and occurred in all areas of
      development. These mismatches were not associated with gestational age at birth,
      neonatal complications, poverty, or estimates of parental experience.
      Professionals should take seriously any expressed developmental concerns by
      parents of high-risk infants. Expressed developmental concerns, however, cannot
      be relied on for developmental screening of high-risk infants.

PMID- 1374429
TI  - MCDI interpretation.

PMID- 1374430
TI  - Intracranial olfactory neuroblastoma: evidence for olfactory epithelial origin.
AB  - AIMS: To determine the possible histogenesis of the intracranial variant of
      olfactory neuroblastoma. METHODS: Four specimens from three cases of intracranial
      olfactory neuroblastoma were studied by light microscopy and immuno
      histochemistry, and electron microscopy in two cases. RESULTS: Light
      microscopical examination showed small cell tumour with additional features of
      epithelioid cells in one case and ganglion cells in another. Olfactory and Homer
      Wright rosettes were present. All the specimens showed a uniform positive
      reaction to neurone specific enolase, S-100, and cytokeratin antibodies. Glial
      fibrillary acidic protein was absent. The salient electron microscopic features
      were the presence of cell junctions, cytoplasmic intermediate filaments, basal
      bodies and cytolasmic processes. Dense cored vesicles were absent. CONCLUSIONS:
      The results strongly support the view that intracranial olfactory neuroblastomas
      are of olfactory epithelial origin and differ from conventional neuroblastomas.

PMID- 1374431
TI  - Use of monoclonal antibody E48 in diagnosing transitional cell carcinoma of
      urinary bladder.
AB  - AIMS: To investigate the localisation of the E48 epitope and to determine the use
      of monoclonal antibody E48 for the identification of transitional cell carcinomas
      (TCC); and to determine if antigenic expression was affected by different
      standard fixation methods. METHODS: Biopsy specimens were labelled with E48 for
      immunoelectron microscopy. One hundred and nineteen tissue samples from 47
      bladder carcinomas were tested for reactivity with E48, using fresh frozen,
      sublimate formalin, and formalin fixed tissue. Thirteen undifferentiated bladder
      tumours and 10 undifferentiated prostatic carcinomas were incubated with E48 and
      prostate specific antigen. RESULTS: Reactivity to E48 was found in all grade 1
      and 2 carcinomas and most (83%) grade 3 tumours. At the ultrastructural level,
      expression was mainly associated with desmosomes and the cytoplasmic membrane.
      The reactivity of E48 was generally strong in fresh frozen tissue samples and
      remained preserved in fixed tissue samples. Ten of the 13 bladder carcinomas
      expressed E48; all prostatic tumours were totally negative. CONCLUSIONS: E48 is a
      sensitive marker for transitional cell carcinoma and suitable for differentiation
      between urothelial and prostatic undifferentiated carcinoma. It can be used in
      routinely processed, formalin fixed, biopsy specimens.

PMID- 1374432
TI  - Biologic correlates of suicidal risk and aggressive behavioral traits.

PMID- 1374433
TI  - Integration of neurobiology and psychopathology in a unified model of suicidal
      behavior.
AB  - Suicidal behavior is the result of a combination of factors that span the domains
      of psychopathology, genetics, early life experience, family interactions, social
      stress, physical illness, and neurobiology. To develop predictive and explanatory
      models of suicidal behavior it is necessary to consider all of these domains. A
      stress-diathesis model is proposed that classifies risk factors for suicidal
      behavior into those that are trait-dependent and those that are state-dependent.
      The timing of suicidal behavior is determined by state-dependent factors. The
      relationship of psychopathologic factors such as severity of depression or
      anxiety to suicide will be discussed. Biologic changes that correlate with
      suicide may be either state- or trait-dependent. Particular emphasis will be
      given to changes in the serotonin system and how these may represent a
      constitutional risk factor as opposed to a state-dependent risk factor for
      suicidal behavior.

PMID- 1374434
TI  - Prediction of suicidal behavior from biologic tests.
AB  - Biochemical studies related with suicidal behavior have mainly dealt with
      monoaminergic and corticosteroidal measures. We used some of these measures in a
      study of 61 suicide attempters who, except for occasional doses of
      benzodiazepines, had been medication free for a mean of 16 days. The monoamine
      metabolites 5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4
      hydroxyphenylglycol were measured in lumbar cerebrospinal fluid (CSF). We found
      that violent suicide attempters (N = 18) had 5-hydroxyindoleacetic acid
      concentrations below the median of all patients, whereas the concentrations of 3
      methoxy-4-hydroxyphenylglycol were mainly above the median. We found no
      significant differences between violent and nonviolent (N = 43) attempters
      concerning CSF homovanillic acid, 24-hour urinary norepinephrine-epinephrine and
      cortisol, activity of monoamine oxidase in platelets, or post-dexamethasone
      plasma cortisol. Four patients completed suicide, and 3 of them had CSF 5
      hydroxyindoleacetic acid concentrations at or below the median. All completed
      suicides had CSF 3-methoxy-4-hydroxyphenylglycol concentrations above the median.
      Urinary measures and platelet monoamine oxidase activity of completed suicides
      were in the higher concentration ranges. Patients who repeated suicidal behavior
      after the index investigation had low 24-hour urinary cortisol levels more often
      than those who did not repeat. Because our subgroups of patients are small, we
      cannot draw any firm conclusions about the value of our CSF and urinary
      biochemical findings predicting suicidal behavior. However, our CSF findings in
      violent suicide attempters are similar to those observed in other studies.

PMID- 1374435
TI  - Distribution of substance P-immunoreactive elements in the preoptic area and the
      hypothalamus of the rat.
AB  - The localization and morphology of neurons, processes, and neuronal groups in the
      rat preoptic area and hypothalamus containing substance P-like immunoreactivity
      were studied with a highly selective antiserum raised against synthetic substance
      P. The antiserum was thoroughly characterized by immunoblotting; only substance P
      was recognized by the antiserum. Absorption of the antiserum with synthetic
      substance P abolished immunostaining while addition of other hypothalamic
      neuropeptides had no effect on the immunostaining. The specificity of the
      observed immunohistochemical staining pattern was further confirmed with a
      monoclonal substance P antiserum. The distribution of substance P immunoreactive
      perikarya was investigated in colchicine-treated animals, whereas the
      distribution of immunoreactive nerve fibers and terminals was described in brains
      from untreated animals. In colchicine-treated rats, immunoreactive cells were
      reliably detected throughout the preoptic area and the hypothalamus. In the
      preoptic region, labeled cells were found in the anteroventral periventricular
      and the anteroventral preoptic nuclei and the medial and lateral preoptic areas.
      Within the hypothalamus, immunoreactive cells were found in the suprachiasmatic,
      paraventricular, supraoptic, ventromedial, dorsomedial, supramammillary, and
      premammillary nuclei, the retrochiasmatic, medial hypothalamic, and lateral
      hypothalamic areas, and the tuber cinereum. The immunoreactive cell groups were
      usually continuous with adjacent cell groups. Because of the highly variable
      effect of the colchicine treatment, it was not possible to determine the actual
      number of immunoreactive cells. Mean soma size varied considerably from one cell
      group to another. Cells in the magnocellular subnuclei of the paraventricular and
      supraoptic nuclei were among the largest, with a diameter of about 25 microns,
      while cells in the supramammillary and suprachiasmatic nuclei were among the
      smallest, with a diameter of about 12 microns. Immunoreactive nerve fibers were
      found in all areas of the preoptic area and the hypothalamus. The morphology,
      size, density, and number of terminals varied considerably from region to region.
      Thus, some areas contained single immunoreactive fibers, while others were
      innervated with such a density that individual nerve fibers were hardly
      discernible. During the last decade, knowledge about neural organization of
      rodent hypothalamic areas and mammalian tachykinin biochemistry has increased
      substantially. In the light of these new insights, the present study gives
      comprehensive morphological evidence that substance P may be centrally involved
      in a wide variety of hypothalamic functions. Among these could be sexual
      behavior, pituitary hormone release, and water homeostasis.

PMID- 1374436
TI  - A projection from the parabigeminal nucleus to the pulvinar nucleus in Galago.
AB  - A projection from the parabigeminal nucleus (Pbg) to the striate-recipient zone
      of the pulvinar nucleus in the prosimian Galago was identified by anterograde and
      retrograde transport methods. In addition to the pulvinar nucleus, Pbg
      projections were found to terminate in layers 4 and 5 of the dorsal lateral
      geniculate nucleus and the central lateral nucleus. All three of these structures
      project to the superficial layers of the striate cortex. Similarities between the
      Pbg in mammals and the nucleus isthmi in nonmammals in connections and
      neurochemistry reinforce the idea that these two nuclei are homologous.

PMID- 1374437
TI  - Polyaxonal amacrine cells of rabbit retina: size and distribution of PA1 cells.
AB  - Type 1 polyaxonal (PA1) amacrine cells have been identified previously in rabbit
      retina, and their morphological characteristics have been described in detail in
      the preceding paper. Like other polyaxonal amacrine cells they bear distinct
      dendritic and axonal branching systems, the latter of which originates in two to
      six thin, branching axons which emerge from or near to the cell body. Unlike
      other types of polyaxonal amacrine cells, however, their branching is stratified
      at the a/b sublaminar border and their cell bodies are most often displaced
      interstitially in the inner plexiform layer (IPL). This report emphasizes
      quantitative features of the population of PA1 cells, documented in Golgi
      impregnated and Nissl-stained retinas, and provides further evidence in Nissl
      preparations for the amacrine-cell nature of polyaxonal amacrine cells. The cell
      bodies of Golgi-impregnated PA1 amacrine cells are relatively large: 12-15
      microns in equivalent diameter over the range extending from the visual streak 6
      mm into ventral retina. Over the same range, dendritic trees are 400-800 microns
      in equivalent diameter, but they are much smaller than the axonal arborizations,
      which extend up to and perhaps beyond 2 mm from the cell body. Interstitial cell
      bodies appropriate to PA1 cells have been identified in Nissl-stained, whole
      mounted rabbit retinas. In the plane of the retina, these are comparable in area
      to smaller medium-size ganglion cells, but their very pale Nissl staining, high
      nuclear/cytoplasmic ratio, and absence of nucleolar staining are all
      characteristics of amacrine cells. Interstitial displacement of presumed PA1
      cells is rare in the visual streak, and the frequency of interstitial cells
      reaches a peak between 1 and 2 mm ventral to the streak. Counts in Nissl-stained
      retinas and estimates from nearest neighbor analyses in these and in Golgi
      impregnated retinas indicate a density of PA1 cells in the range of 15-16
      cells/mm2 at about 2 mm ventral to the streak, when an estimated 25% shrinkage of
      the material is taken into account. Dendritic field overlap, based upon this
      estimate, is calculated to be about fourfold, while a lower bound to estimates of
      the overlap of axonal arborizations is nearly an order of magnitude higher. Many
      similarities are noted in a qualitative and quantitative comparison of PA1
      amacrine cells in rabbit and monkey retinas. In assessing the contribution of the
      structural organization of PA1 amacrine cells to their possible functional
      role(s), it is notable that their appearance conforms not to amacrine cells as
      commonly viewed, but to a more conventional model of neuronal dynamic
      polarization.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374438
TI  - Polyaxonal amacrine cells of rabbit retina: PA2, PA3, and PA4 cells. Light and
      electron microscopic studies with a functional interpretation.
AB  - Polyaxonal (PA) amacrine cells are a new class of amacrine cell bearing one to
      six branching, axon-like processes that emerge from the cell body or dendritic
      trees within 50 microns of the cell body. These slender processes of uniform
      caliber branch at right angles and in many respects closely resemble the axons of
      Golgi type II cells found elsewhere in the brain. Of the four types of polyaxonal
      amacrine cell that we have recognized in rabbit retina, two have been described
      previously in brief communications. One of these, the PA1 amacrine cell with its
      interstitially displaced cell body, located in the inner plexiform layer (IPL),
      has been analyzed extensively in two preceding reports. This paper concerns PA2,
      PA3, and PA4 amacrine cells. Type 2 polyaxonal (PA2) amacrine cells, identified
      in Golgi preparations of whole-mounted rabbit retinas, have smaller cell bodies
      (9-14 microns) than the other three types and these are always displaced to the
      ganglion cell layer (GCL) or the inner border of the inner plexiform layer (IPL).
      The dendritic fields of PA2 cells are also smaller than those of other PA
      amacrine cells, and most of their sparse dendritic branching is narrowly
      stratified at the border of strata (S) 4 and 5. Some members of this more
      heterogeneous amacrine cell "type" are bistratified, however, and more highly
      branched with terminal branches rising to end in S1. PA2 amacrine cells bear a
      scattering of small dendritic spines and may also exhibit complex dendritic
      appendages arising at the ends of terminal branches in proximal regions of the
      dendritic tree. PA2 cells emit one to three axons from the proximal dendritic
      tree, and about half of the cells bear a single axon. Type 3 polyaxonal (PA3)
      amacrine cells resemble PA1 cells in the large size of their cells bodies (11-16
      microns) and dendritic fields, but differ from the latter in placement of cell
      bodies, which is in the GCL, and dendritic and axonal stratification, which is
      multistratified, ranging from S4 to S1, with a concentration in S3 or S4 and a
      variable contribution to S1. PA3 cells differ from PA1 cells in several other
      respects, including dendritic branching which occurs at higher frequency and is
      biased toward temporal retina, and in characteristic bristling dendritic spines,
      clustered in the intermediate regions of the dendritic tree, that are longer,
      more variable in appearance and more tightly clustered than the small, uniform
      spines of PA1 cells that are clustered on proximal dendrites.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1374439
TI  - Galanin-like innervation of rat submandibular and sublingual salivary glands:
      origin and effect on acinar cell membranes.
AB  - The distribution and source of a galanin-like innervation of rat salivary glands
      has been examined. Additionally, submandibular and sublingual acinar cell
      membrane responses to galanin or a cholinergic agonist were studied. Galanin
      immunoreactive fibers were observed throughout the submandibular and sublingual
      glands in association with ducts and acini. A subset of submandibular ganglion
      cells expresses galanin immunoreactivity. Parasympathectomy resulted in a marked
      decrease in galanin immunoreactivity in the glands. Sympathectomy resulted in
      marked reduction of dopamine beta-hydroxylase immunoreactivity with no
      appreciable change in galanin immunoreactivity. Retrograde labeling experiments
      demonstrated that galanin-immunoreactive sensory neurons in the trigeminal
      ganglion do not innervate the submandibular or sublingual gland. These results
      indicate that the galanin-like innervation of rat salivary glands is derived from
      parasympathetic nerves to the glands. Since rat sublingual glands contain largely
      mucous acini while rat submandibular gland acini are seromucous,
      electrophysiological responses to galanin and the muscarinic agonist,
      bethanechol, were compared. Agonist-induced voltage shifts varied between the two
      glands. The galanin-induced response at the level of the resting membrane
      potential in submandibular acinar cells was a hyperpolarization, while that in
      sublingual acinar cells was a depolarization. There was also a greater voltage
      dependence to the galanin-induced submandibular response than to the sublingual
      response. Differences were also noted in the acinar cell response to cholinergic
      stimulation between these glands. These results demonstrate the existence of a
      galanin-like innervation to salivary glands that may be functionally relevant.
      Moreover, the results challenge the idea that agonist-induced membrane responses
      are similar among acinar cells of different glands.

PMID- 1374440
TI  - Distribution of neurotensin immunoreactivity within the human amygdaloid complex:
      a comparison with acetylcholinesterase- and Nissl-stained tissue sections.
AB  - In a previous study, we reported marked depletion of neurotensin-immunoreactivity
      (NT-IR) within selected regions of the amygdala of patients with Alzheimer's
      disease. The significance of these observations was partly obscured largely
      because we lacked a thorough understanding of the innervation pattern of
      neurotensin in the normal human amygdala. Accordingly, in the present study, we
      used a polyclonal antibody against neurotensin to characterize the distribution
      and morphology of neurotensin-immunoreactive neuronal elements within the human
      amygdaloid complex. NT-IR occurred in a topographic manner that respected the
      cytoarchitectural boundaries of the amygdaloid subregions as defined by Nissl
      staining and acetylcholinesterase histochemistry. Most NT-IR in the amygdala was
      contained within beaded fibers and dot-like puncta. Within the subnuclei of the
      amygdala, immunoreactive neuritic elements were most dense within the central
      nucleus followed by the medial nucleus and intercalated nuclei. The anterior
      amygdaloid area, basal complex, paralaminar nucleus, cortical nucleus, cortical
      amygdaloid transition area, and amygdalohippocampal area contained moderate
      densities of immunoreactivity. The accessory basal and lateral nuclei exhibited
      scant NT-IR. Immunoreactive neurons were found only within the anterior
      amygdaloid area and the central, medial, intercalated, and lateral capsular
      nuclei. The distribution of NT-immunoreactive processes and cell bodies within
      selected regions of the amygdala provides an anatomical substrate that may
      explain, in part, the neuromodulatory actions of neurotensin upon autonomic,
      endocrine, and memory systems.

PMID- 1374441
TI  - Astrocytes in cat visual cortex studied by GFAP and S-100 immunocytochemistry
      during postnatal development.
AB  - A monoclonal antibody to glial fibrillary acidic protein (GFAP) and a polyclonal
      antiserum to the S-100 protein were used to study the expression of these
      astrocytic proteins in the postnatal visual cortex of the cat. Three changes in
      antigen expression of these astroglial markers could be distinguished over
      development. First, the density of cells in the white matter, which are heavily
      labelled with both antibodies from birth until adulthood, diminishes after the
      third postnatal weeks. By intracellular filling with Lucifer Yellow the reduction
      of the cell density can be attributed to the disappearance of large astrocytes
      with a morphology of transforming radial glia, present only in early postnatal
      development. Second, heavily labelled, large cells present in the grey matter at
      the seventh postnatal day have disappeared by the fifth postnatal week. On the
      basis of their morphology these cells can also be classified as radial glial
      cells. Finally, astroglial cells of the adult-like stellate form appear to be
      labelled in the cortical layers between the third and seventh postnatal weeks.
      While the density of these cells and the S-100 immunoreactivity of the cell
      bodies is adult-like at the fourth postnatal week, there is a gradual increase of
      the staining intensity with the GFAP antibody up to the seventh postnatal week.
      This developmental period is paralleled by the appearance of S-100-positive
      astrocytic processes. The gradual expression of GFAP immunoreactivity and the
      increased expression of S-100 is interpreted as reflecting the time course of
      astrocytic maturation. A possible relation of the maturation of astrocytes and
      cortical development, both of which are prominent in the time period between the
      third and seventh postnatal week, is discussed.

PMID- 1374442
TI  - Distribution of neurons expressing neurokinin B in the rat brain:
      immunohistochemistry and in situ hybridization.
AB  - Neurokinin B (NKB) belongs to the family of neuropeptides named tachykinins.
      Members of this family such as substance P or neurokinin A have been proposed to
      function as neurotransmitters or neuromodulators. Searching for possible sites of
      action of NKB in the central nervous system, we have now investigated its
      distribution within the rat brain by immunohistochemical techniques and in situ
      hybridization. For immunohistology two different antisera directed against amino
      acid sequences within preprotachykinin B were used. One antiserum had been raised
      against a synthetic derivative of NKB; the other one was directed towards the
      amino acids 50-79 of preprotachykinin B, which are referred to as peptide 2.
      Essentially the same distribution of immunoreactive perikarya was obtained with
      both antisera and it closely corresponded to the cellular localization of
      preprotachykinin B mRNA. Neurons containing NKB immunoreactivity and mRNA were
      present in many areas including cerebral cortex, hippocampal formation,
      amygdaloid complex, bed nucleus of the stria terminalis, ventral pallidum,
      habenula, medial preoptic area, arcuate nucleus, and lateral mammillary bodies.
      Dense immunoreactive fibers were observed in various parts of the brain and were
      most prominent in the olfactory bulb and tubercle, the lateral olfactory tract,
      medial hypothalamus, around blood vessels of the median eminence and
      interpeduncular nucleus, amygdaloid nuclei, stria terminalis, subbrachial
      nucleus, and medial geniculate nucleus. Fibers of less intense staining were seen
      among other brain areas in the substantia nigra, the reticular formation, and the
      area of the nucleus of the solitary tract. Surgical lesion of the fasciculus
      retroflexus revealed that the dense fiber network observed in the interpeduncular
      nucleus originates from the ventral and dorsal parts of the medial habenula. Our
      data suggest a widespread and distinct distribution of neurons expressing NKB
      within the central nervous system, suggesting possible neuromodulatory roles of
      this neuropeptide for various brain functions.

PMID- 1374443
TI  - Distribution of neuropeptide Y, substance P, and choline acetyltransferase in the
      developing visual system of the pigeon and effects of unilateral retina removal.
AB  - The distribution of three neuroactive substances, neuropeptide Y, substance P,
      and choline acetyltransferase, was studied by immunocytochemical methods in
      central visual regions of adult, developing, and ablated pigeon brains. In normal
      adult brains, neuropeptide Y-positive cells and processes were present in the
      nucleus pretectalis, the nucleus of the basal optic root, the nucleus of the
      marginal optic tract, and the visual Wulst. Substance P-positive cells and
      processes were found in the optic tectum and in the visual Wulst. Stained fibers
      and terminal-like processes, but no cells, were also observed in several visual
      thalamic nuclei. Choline acetyltransferase-positive cells and processes were
      located in the optic tectum, visual Wulst, the nucleus isthmo opticus, nucleus
      isthmi and certain visual thalamic nuclei. Cholinergic fibers and processes, but
      no cells, were present in the nucleus principalis precommissuralis, the
      supraoptic decussation, and the nucleus lentiformis mesencephali, pars
      magnocellularis. In the course of development, the distribution of
      immunoreactivity for all three substances was found to vary. These changes often
      involved either progressive increases or decreases in the density of labeled
      cells, neuropil and/or terminal-like profiles. Experiments with retina ablated
      pigeons clearly demonstrated that changes in the normal pattern of
      immunoreactivity distribution only occurred if the retina was removed immediately
      after hatching, i.e., before retinofugal connections have been established. The
      adult pattern of immunoreactivity for all three substances appears to be reached
      at about the same time that the anatomical and functional maturation of the
      pigeon visual system is completed. The present results suggest that this temporal
      correlation reflects the important role that retinal afferents play in the
      development of these putative peptidergic and cholinergic systems.

PMID- 1374444
TI  - Rapid growth of astrocytic processes in N. magnocellularis following cochlea
      removal.
AB  - Removal of the cochlea or pharmacological blockade of eighth nerve activity in
      young postnatal chickens results in rapid transneuronal cell death and atrophy in
      neurons of n. magnocellularis. The present experiments were designed to examine
      the influence of afferent input on astrocyte structure in n. magnocellularis.
      Young chickens were subjected to unilateral cochlea removal. At times ranging
      from 5 minutes to 72 hours later, the brainstems were histologically processed
      with a polyclonal antibody against glial fibrillary acidic protein (GFAP). A
      second group of chick brainstems was impregnated by a Golgi method 6 hours after
      unilateral cochlea removal and impregnated three-dimensional reconstructions were
      made of glial cells in n. magnocellularis (NM). Analyses of GFAP positive
      processes in NM revealed an observable increase in the number of astrocytic
      processes at the borders of the nucleus within 30 minutes of cochlea removal and
      a twofold increase in GFAP + glial processes by 6 hours. A secondary increase in
      the number and density of GFAP + processes occurred between 24 and 72 hours
      following cochlea removal, during the period of axonal degeneration, and
      transneuronal cell atrophy and death. Analyses of astrocytes impregnated by the
      Golgi method revealed that individual glial cells had increased their total
      process length and the number of processes by approximately twofold by 6 hours
      after cochlea removal. These results suggest that the structure of astrocytes is
      rapidly and dramatically influenced by the level of excitatory activity in a
      neuronal system. Furthermore, the similarity of results obtained with GFAP
      immunohistochemistry and three-dimensional reconstruction of astrocytes provides
      evidence that the short-term changes observed following cochlea removal represent
      the actual growth of glial processes. We speculate that modulations in glial
      processes as a function of afferent activity may act to influence synaptic
      efficacy.

PMID- 1374445
TI  - CD19 regulation of human B cell responses. B cell proliferation and antibody
      secretion are inhibited or enhanced by ligation of the CD19 surface glycoprotein
      depending on the stimulating signal used.
AB  - The regulation of human B cell proliferation and differentiation by the CD19
      surface glycoprotein was investigated. As expected, proliferation induced by
      costimulation with anti-IgM plus IL-4 or IL-2, or with G28.8 antibody plus IL-4
      was inhibited by antibody ligation of CD19. In contrast, proliferation of
      tonsillar B cells to mitogenic doses of PMA (5 ng/ml) or to EBV were enhanced,
      and proliferation of B cell lines to BCGF(low) was unaffected. Similarly,
      specific antibody responses by tonsillar B cells to influenza virus, and Ig
      secretion by the CESS lymphoblastoid cell line in response to IL-6 were
      inhibited, whereas polyclonal Ig production in response to EBV was enhanced.
      These results show that human B cell responses may be inhibited or enhanced by
      CD19 depending on the stimulating signal used. The difference in response to CD19
      ligation did not depend on whether proliferation or differentiation was being
      measured, or whether stimulation was by surface Ig. In experiments using PMA as a
      T cell independent mitogen, it was found that ligation of CD19 inhibited
      proliferation of B cells costimulated with low doses of PMA plus G28.5 (CD40)
      antibody, but enhanced the response to higher (mitogenic) doses with or without
      costimulation with G28.5. The change from inhibition to enhancement occurred over
      a very small increase in PMA dose (0.5-1.0 ng/ml) that corresponded exactly to
      the lowest dose required for mitogenic activity. Finally, we showed that CD19
      ligation inhibited the increase in surface expression of CD23, but not IgM,
      induced by IL-4, showing that CD19 ligation can have opposed effects on different
      responses to the same signal. Together our results suggest that CD19 activation
      of human B cells interacts with other signaling events to enhance or inhibit the
      subsequent response.

PMID- 1374446
TI  - Role of endogenous peptides in murine allogenic cytotoxic T cell responses
      assessed using transfectants of the antigen-processing mutant 174xCEM.T2.
AB  - One model to explain the high frequency of alloreactive T cells proposes that
      allogeneic MHC molecules are recognized together with host cell-derived peptides.
      A model system was developed to investigate the relevance of this mechanism by
      expression of H-2Dd or H-2Ld in 174xCEM.T2 (T2) cells. This human cell line
      contains a mutation in its Ag-processing pathway that should restrict the
      association of endogenous peptides with cell surface class I molecules. CTL
      generated by stimulating C57BL/6 (H-2b) responder cells with H-2Dd or H-2Ld
      transfectants of the human B cell line C1R or the murine T cell lymphoma EL4 were
      assayed for their ability to recognize alloantigenic determinants on these
      transfectants. The major fraction of the H-2Dd-specific allogeneic CTL response,
      generated in a MLC or under clonal limiting dilution conditions, was composed of
      T cells that recognized H-2Dd expressed on C1R or EL4 cells, but failed to
      recognize this molecule on T2 cells. Clonal analysis indicated that approximately
      one-third of these CTL recognized determinants that were unique to H-2Dd
      expressed on C1R stimulator cells whereas the remainder recognized determinants
      that were also found on EL4 transfectants. Less than 10% of H-2Dd-reactive CTL
      recognized the T2 transfectant, and these clones also killed C1R-Dd and EL4-Dd.
      This result suggests that the great majority of H-2Dd-specific alloreactive CTL
      recognize determinants that are formed by a complex of H-2Dd with endogenous
      peptides that are absent or significantly reduced in T2 cells. Based on
      recognition of human or murine transfectants, these CTL exhibit some level of
      specificity for the structure or composition of the bound peptides. Examination
      of allogeneic CTL specific for H-2Ld revealed populations similar to those
      described for H-2Dd. In addition, a major new population was present that
      recognized determinants shared between C1R-Ld and T2-Ld but not present on EL4
      Ld. These results are consistent with the idea that the alloreactive response to
      H-2Ld is also largely dependent on the presence of bound peptide. However, they
      also may indicate that the H-2Ld molecule expressed on T2 cells is occupied by
      one or more peptides that are shared with other human, but not murine, cells. The
      significance of these results to current models of alloreactivity is discussed.

PMID- 1374447
TI  - Effect of point mutations in the native simian virus 40 tumor antigen, and in
      synthetic peptides corresponding to the H-2Db-restricted epitopes, on antigen
      presentation and recognition by cytotoxic T lymphocyte clones.
AB  - The effects on CTL recognition of individual amino acid substitutions within
      epitopes I, II, and III of SV40 tumor Ag (T Ag) were examined. Epitope I spans
      amino acids 207 to 215, and epitope II/III is within residues 223 to 231 of SV40
      T Ag. An amino acid substitution at position 207 (Ala----Val) or 214 (Lys----Glu)
      of SV40 T Ag expressed in transformed cells resulted in loss of epitope I,
      recognized by CTL clone Y-1. The amino acid substitution at residue 214 in the
      corresponding synthetic peptide, LT207-215(214-Lys----Glu), also led to loss of
      recognition by CTL clone Y-1. The recognition, by CTL clone Y-1, of peptides
      LT207-215 and LT207-217 with an Ala----Val substitution at position 207 was
      severely affected. Peptides LT205-215 and LT205-219 with the Ala----Val
      substitution at residue 207 were, however, recognized by CTL clone Y-1,
      suggesting that residues 205 and 206 may be involved in presentation of site I.
      Alteration of residue 224 (Lys----Glu) in the native T Ag resulted in loss of
      recognition by both CTL clones Y-2 and Y-3. However, a peptide corresponding to
      epitope II/III with an identical amino acid substitution at residue 224 provided
      a target for CTL clone Y-3 but not clone Y-2. A change of Lys----Gln at residue
      224 in both the native protein and a synthetic peptide caused loss of recognition
      by CTL clone Y-2 but not CTL clone Y-3. Further, an amino acid substitution of
      Lys----Arg at position 224 of the native T Ag decreased recognition of epitope
      II/III by CTL clones Y-2 and Y-3 but had no effect on recognition of a synthetic
      peptide bearing the same substitution. These results indicate that the
      mutagenesis approach, resulting in identical amino acid substitutions in the
      native protein and in the synthetic peptides, may provide insight into the role
      of individual residues in the processing, presentation, and recognition of CTL
      recognition epitopes.

PMID- 1374448
TI  - Persistent productive HIV-1 infection of a CD4- human fetal thymocyte line.
AB  - Human fetal thymuses were obtained from abortuses of HIV-1 seronegative females.
      Thymocytes were isolated and cultured for 2 days with PHA. Thereafter, the
      culture was divided and half of the cells were exposed to the HIV-1 RF isolate
      for 4 h. After this incubation period, the HIV-1 exposed and nonexposed control
      cells were cultured in RPMI 1640 supplemented with IL-2 for 30 days and
      subsequently maintained in RPMI without the addition of growth factors. Long term
      culture of both HIV-1 exposed and control thymocytes has yielded two cell lines
      that have been maintained for more than 3 yr without the addition of growth
      factors. Flow cytometry using mAb that recognize T cell differentiation markers
      was used to analyze cell phenotypes. The HIV-1 exposed thymocyte cell line
      (E88/RF) was shown to be HIV-1 infected by p24 ELISA, reverse transcriptase
      activity, immunocytochemistry, in situ hybridization, polymerase chain reaction,
      electron microscopy, and to produce infectious particles by a syncytial forming
      assay. The non-HIV-1-exposed thymocyte cell line (T412) has remained negative by
      all criteria for HIV-1 infection. Flow cytometry showed the T412 cells to be
      positive for the T cell markers CD45, CD38, and CD4 but negative for all other
      markers tested. The E88/RF cells are positive for CD45 and CD38 but negative for
      CD4 and other markers. These data report the isolation of two human fetal
      thymocyte cell lines; one uninfected and susceptible to HIV-1 infection, and the
      other persistently and productively infected with HIV-1 with little
      cytopathology. These findings suggest that HIV-1 can persistently infect early T
      cells and may alter T cell differentiation.

PMID- 1374449
TI  - Lung injury after deposition of IgA immune complexes. Requirements for CD18 and L
      arginine.
AB  - Acute lung injury produced by deposition of IgA immune complexes is complement
      dependent, neutrophil-independent, oxygen radical-mediated, and may be a result
      of the formation of the hydroxyl radical (HO) generated directly or indirectly
      from activated lung macrophages. The current studies were designed to evaluate
      further the pathophysiologic events that occur after intrapulmonary deposition of
      IgA immune complexes. Pretreatment of rats with the human recombinant soluble
      complement receptor-1 resulted in marked attenuation of IgA immune complex
      induced lung injury. Intravenous administration of antibody to CD18, but not
      antibody to CD11b, was highly protective against lung injury. Treatment of
      animals with either anti-endothelial leukocyte-adhesion molecule-1 or anti-TNF
      alpha, both of which were highly protective against IgG immune complex-induced
      lung injury, had no protective effects in the model of IgA immune complex-induced
      lung injury. Immunohistochemical analysis revealed up-regulation of the
      endothelial leukocyte adhesion molecule-1 in the pulmonary vasculature after
      deposition of IgA immune complexes. This up-regulation was TNF-alpha-dependent.
      The arginine analog, NG-monomethyl-L-arginine, was highly protective against IgA
      immune complex-induced lung injury. This protective effect was reversed by the co
      presence of L-arginine (but not D-arginine). Protective interventions against IgA
      immune complex-induced lung injury were inversely correlated with the numbers of
      macrophages that could be retrieved by lung lavage. These data suggest
      fundamental differences in the pathogenesis of lung injury after intrapulmonary
      deposition of IgA immune complexes, as compared with injury caused by deposition
      of IgG immune complexes. In the latter, neutrophils, intrapulmonary generation of
      TNF-alpha, and up-regulation of pulmonary vascular endothelial leukocyte-adhesion
      molecule-1 are required for the full development of lung injury, whereas no such
      requirements appear in the case of IgA immune complex-induced lung injury. Full
      expression of IgA immune complex-induced lung injury also appears to require L
      arginine, suggesting a possible role for nitric oxide or its derivatives in
      events ultimately leading to injury.

PMID- 1374450
TI  - Structural and functional analysis of monomorphic determinants recognized by
      monoclonal antibodies reacting with the HLA class I alpha 3 domain.
AB  - To identify mAb reacting with the HLA class I alpha 3 domain, 14 mAb recognizing
      monomorphic determinants expressed on HLA-A, B, and C Ag or restricted to HLA-B
      Ag were screened in indirect immunofluorescence with mouse L cells expressing HLA
      B7/H-2Kb chimeric Ag. mAb CR1S63, CR10-215, CR11-115, and W6/32 were found to
      react with the HLA class I alpha 3 domain in addition to the alpha 2 domain. mAb
      Q1/28 and TP25.99 were found to react only with the HLA class I alpha 3 domain.
      The determinants recognized by the six mAb were mapped on the HLA class I alpha 3
      domain by indirect immunofluorescence staining of L cells expressing H-2Kb Ag
      containing different segments of the HLA-B7 alpha 3 domain chimerized with the H
      2Kb alpha 3 domain. mAb TP25.99 reacts with chimeric Ag containing the HLA-B7 184
      to 199 stretch, mAb CR10-215 and CR11-115 react with chimeric Ag containing the
      HLA-B7 184 to 246 stretch, mAb CR1S63 and Q1/28 react with chimeric Ag containing
      the HLA-B7 184 to 256 stretch, and mAb W6/32 reacts with chimeric Ag containing
      the whole HLA-B7 alpha 3 domain. Functional analysis using human CD8 alpha
      bearing mouse H-2Kb-specific T cell hybridoma cells (HTB-Leu2) showed that only
      mAb TP25.99 inhibited IL-2 production by HTB-Leu2 cells stimulated with L cells
      expressing KbKbB7 Ag. This inhibition may occur because of the spatial proximity
      of the determinant defined by mAb TP25.99 to the CD8 alpha binding loop and/or
      because of change(s) in the conformation of the CD8 alpha binding loop induced by
      the binding of mAb TP25.99 to the HLA class I molecule. Furthermore, mAb TP25.99
      inhibited the cytotoxicity of CD8-dependent and CD8-independent CTL clones. These
      results indicate that mAb TP25.99 has unique specificity and functional
      characteristics. Therefore it represents a valuable probe to characterize the
      role of the HLA class I alpha 3 domain in immunologic phenomena.

PMID- 1374451
TI  - Epitope mapping of Streptococcus mutans SR protein and human IgG cross-reactive
      determinants, by using recombinant proteins and synthetic peptides.
AB  - alpha-Hemolytic oral streptococci are known to possess a family of cell surface
      cross-reactive proteins termed Ag I/II, having a molecular mass of approximately
      180 to 210 kDa. These proteins are implicated in bacterial adherence to various
      oral tissues, and we showed recently that the SR protein, an I/II Ag-related
      protein, from Streptococcus mutans OMZ 175 serogroup f possesses Ag mimicry with
      human IgG. In this study, regions of the SR protein encoding the cross-reactive
      epitope(s) were analyzed by expressing selected restriction fragments from the
      cloned sr gene. The three SR-derived polypeptides reacted in ELISA with anti-SR
      rabbit IgG, whereas only the two polypeptides located along the carboxyl-terminal
      two thirds of the SR protein reacted with anti-human IgG rabbit IgG. In order to
      locate more precisely the human IgG-cross-reactive region, we synthesized six
      peptides, on the basis of the recently determined complete nucleotide sequence of
      the sr gene. Among these peptides, peptide 2, corresponding to the alanine-rich
      repeating amino-terminal region, peptide 3, located in the three tandem proline
      rich regions, and peptide 6, located near the cell wall-spanning region, were the
      most interesting in term of antigenicity and immunogenicity. Anti-peptide 2, 3,
      and 6 rabbit IgG reacted with free SR and with cell wall-associated SR. Peptide
      1, located near the amino terminus, was poorly immunogenic. Peptides 4 and 5,
      located in the putative human IgG-cross-reactive region, were immunogenic;
      however, anti-peptide 4 rabbit IgG reacted only weakly with SR or human IgG,
      whereas anti-peptide 5 rabbit IgG reacted strongly with SR and human IgG, and
      peptide 5 was recognized by anti-SR and anti-human IgG rabbit IgG. These results
      confirm the cell surface accessibility of this epitope and its potential
      participation in eliciting, in rabbits, anti-SR IgG cross-reactive with human
      IgG.

PMID- 1374452
TI  - Characterization of HTLV-I in vivo infected T cell clones. IL-2-independent
      growth of nontransformed T cells.
AB  - Mononuclear cells from subjects infected with human T lymphotrophic virus type I
      (HTLV-I) display a unique ability to proliferate in vitro in the absence of
      mitogens or exogenous growth factors. Subjects who have developed an HTLV-I
      associated myelopathy (HAM) show an even higher degree of spontaneous
      proliferation concomitant with transcription of the HTLV-I provirus. The
      mechanism underlying HTLV-I-induced T cell activation was investigated by
      characterizing a series of HTLV-I-infected T cell clones generated from the blood
      of subjects with HAM. Approximately 15% of the T cell clones generated were HTLV
      I infected as determined by polymerase chain reaction and Southern blotting.
      Infected T cell clones displayed altered growth kinetics as they continued to
      incorporate tritiated thymidine 7 to 14 days after stimulation, a time when
      noninfected T cell clones had returned to a resting state. This was not due to
      transformation as all the T cell clones required periodic restimulation with
      mitogens and feeder cells for continued growth. Although HTLV-I-infected T cell
      clones showed increased expression of the IL-2 receptor p55 chain, the
      spontaneous clonal proliferation was not inhibited by anti-IL-2 receptor mAb.
      Moreover, the spontaneous clonal proliferation was insensitive to cyclosporin A
      and FK 506 while being highly sensitive to rapamycin, which is known to inhibit
      IL-2-mediated signaling. Together these results demonstrate that IL-2 is not
      required for the HTLV-I-induced spontaneous clonal proliferation and further
      suggest that HTLV-I may induce signaling pathways replacing an IL-2 receptor
      signal proximal to the site of action of rapamycin.

PMID- 1374453
TI  - Cloning of a novel tumor necrosis factor-alpha-inducible primary response gene
      that is differentially expressed in development and capillary tube-like formation
      in vitro.
AB  - TNF is a proinflammatory cytokine that has pleiotropic effects on cells and
      tissues, mediated in large part by alterations in target tissue gene expression.
      We have used the technique of differential hybridization to identify several
      primary response genes induced by TNF in human umbilical vein endothelial (HUVE)
      cells, a cell type that is profoundly activated by cytokine treatment. One of
      these cDNA, designated B94, detects a rapidly and transiently induced 4-kb
      transcript in TNF-treated HUVE cells, and this transcript is superinduced in the
      concomitant presence of cycloheximide. Other proinflammatory stimuli including IL
      1 beta and LPS are also able to induce B94 mRNA expression. Nuclear run-on
      experiments demonstrate that TNF induction of B94 transcript occurs primarily at
      the level of transcriptional activation. Further, B94 is shown to be a single
      copy gene that is evolutionarily conserved. The gene is localized to the q32
      region of chromosome 14, a region that is often rearranged in lymphoid neoplasms.
      B94 transcript expression is also found to be regulated during mouse development
      and in an in vitro model of endothelial capillary tube formation. Developmental
      regulation occurs most prominently in mouse embryonic liver and kidney, and a
      second smaller form of B94 transcript is detected in the placenta and testes. B94
      and other TNF-responsive transcripts are also induced during capillary tube
      formation suggesting overlap between genes induced by TNF and those induced
      during angiogenesis. Sequence analysis of the B94 cDNA reveals an open reading
      frame encoding a 73-kDa polypeptide that has no homology to any known protein.
      Polyclonal antisera directed against the carboxyl-terminal portion of the B94
      protein immunoprecipitates a protein of the predicted molecular mass both from
      COS cells transfected with a B94 expression vector and from TNF-treated HUVE
      cells.

PMID- 1374454
TI  - Prolonged interferon-gamma application by subcutaneous infusion in cancer
      patients: differential response of serum CD14, neopterin, and monocyte HLA class
      I and II antigens.
AB  - This study reports on biological response modification induced by prolonged
      continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN
      gamma) with particular attention to changes of soluble CD14. This glycoprotein
      with an unknown function is derived from myeloid cells carrying membrane CD14,
      which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP)
      complexes. Fifteen metastatic cancer patients received weekly escalating doses of
      rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400
      micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was
      higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose.
      Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14,
      neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte
      HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma
      concentrations increased 20-fold within 4 weeks of therapy. The levels were
      correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological
      markers, two patterns were observed. First, serum CD14 concentration and
      expression of monocyte HLA class II antigens increased significantly during the
      first week, and marker expression correlated with serum IFN-gamma levels (p less
      than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment
      levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma
      concentrations. Second, serum neopterin and beta 2-microglobulin concentrations
      as well as monocyte HLA class I expression also increased significantly within
      the first week, but remained elevated thereafter without any further dose
      relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374455
TI  - Resistance to interferon-alpha in a mouse B-cell lymphoma involves DNA
      methylation.
AB  - Resistance to interferon-alpha (IFN-alpha) in the 38C13 B-lymphoma cell line
      results in the loss of antiviral, antiproliferative, and immune regulatory
      functions of IFN-alpha. Mutagenesis with ethylmethylsulfonic acid (EMS), which
      can induce point mutations in DNA, increases the frequency of resistance to IFN
      alpha 20 to 40-fold. In contrast, treatment with 5-azacytidine, which causes
      hypomethylation of DNA, reduces the frequency of resistance to 5-10% of control.
      Furthermore, 5-azacytidine treatment reverts IFN-alpha-resistant cells to the IFN
      alpha-sensitive state. Resistance to IFN-alpha occurs spontaneously at a rate of
      approximately 3 x 10(-6) variants/cell.generation, and is stable for more than 30
      passages without selection in IFN-alpha. There is no evidence that gene
      amplification contributes to the high rate of resistance to IFN-alpha in these
      cells. These results indicate that DNA mutation and methylation are important in
      the development of IFN-alpha resistance in these cells.

PMID- 1374456
TI  - HIV-1 reverse transcriptase inhibiting antibody titer in serum: relation to
      disease progression and to core-antibody levels.
AB  - A new assay for detecting inhibition of reverse transcriptase activity (the RT-i
      REA) was developed. This assay was standardized for screening serum samples for
      reverse transcriptase inhibiting antibodies (RT-iAb). High specificity (100%) and
      sensitivity (greater than 98%) were achieved with samples from HIV-negative
      individuals and HIV-infected individuals. The RT-i REA was also used in a study
      of the titers of RT-iAb in serum samples obtained from 33 HIV-infected homosexual
      men. The results confirmed the relation between decreasing RT-iAb levels and
      progression to late stages of the disease. Furthermore, a falling RT-iAb titer
      was observed in 14 of 15 individuals experiencing periods of severe clinical
      symptoms attributed to HIV-activity. In 7 of the patients the decline in RT-iAb
      titer began prior to severe clinical symptoms. The fall in RT-iAb titer also
      correlated with a reduction in core Ab level. The core Ab level has previously
      been reported to be a disease progression marker with considerable prognostic
      value. However, whereas all patients were positive for RT-iAb, 8 of the 33
      patients did not have detectable core Ab. The use of RT-iAb titer as a marker of
      disease progression is discussed.

PMID- 1374457
TI  - Local synaptic circuits and epileptiform activity in slices of neocortex from
      children with intractable epilepsy.
AB  - 1. Single and dual intracellular recordings were performed in neocortical slices
      obtained from tissue samples surgically removed from children (8 mo to 15 yr) for
      the treatment of intractable epilepsy. Electrical stimulation and glutamate
      microapplication were used to study local synaptic inputs to pyramidal cells. 2.
      In recordings with potassium-acetate electrodes, activation of presynaptic
      neocortical neurons with glutamate microdrops did not elicit a clear increase in
      postsynaptic potentials (PSPs) but did suppress current-evoked repetitive spike
      firing in recorded neurons. Bicuculline (10 microM) blocked this effect,
      suggesting it was caused by the activation of presynaptic gamma-aminobutyric acid
      (GABA) cells. In recordings with KCl electrodes, glutamate microdrops elicited an
      increase in the frequency and amplitude of depolarizing PSPs. Bicuculline (5-10
      microM) blocked the glutamate-evoked PSPs, suggesting they were reversed GABAA
      receptor-mediated inhibitory postsynaptic potentials (IPSPs). In one cell
      recorded with a KCl electrode (total n = 8), current-evoked spike trains elicited
      afterdischarges of reversed IPSPs, thus revealing a recurrent inhibitory circuit.
      Therefore local inhibitory synaptic circuits were robust and could be observed in
      tissue from patients as young as 11 mo. 3. In addition to short-latency (10-25
      ms), monosynaptic excitatory postsynaptic potentials (EPSPs), electrical
      stimulation at low intensities sometimes elicited delayed EPSPs (20-60 ms). When
      GABAA-receptor-mediated synaptic inhibition was partially reduced in bicuculline
      (5-10 microM), electrical stimulation evoked large EPSPs at long and variable
      latencies (100-300 ms). Glutamate microapplication caused an increase in the
      frequency and amplitude of EPSPs; preliminary results suggest that glutamate
      microdrops were less likely to evoke EPSPs in tissue from younger patients (8-12
      mo) than in slices from patients greater than 4 yr. Evidence for local excitatory
      synaptic circuits was thus found when synaptic inhibition was partially reduced.
      4. After further reduction of inhibition in bicuculline (5-50 microM), electrical
      stimulation elicited epileptiform bursts. In pairs of simultaneously recorded
      neurons, bursts were generated synchronously from long-latency EPSPs (100-300 ms)
      in slices from patients as young as 8 mo. Reflected EPSPs at very long and
      variable latencies (500-1,100 ms) and repetitive epileptiform bursts could be
      evoked synchronously in pairs of cells. Glutamate activation of local presynaptic
      neurons elicited robust epileptiform events in recorded cells. This was seen in
      slices from patients as young as 16 mo. 5. These data provide physiological
      evidence for the presence of local inhibitory and excitatory synaptic circuits in
      human neocortex at least as early as 11 and 8 mo, respectively.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1374458
TI  - Heterogeneous calcium currents and transmitter release in cultured mouse spinal
      cord and dorsal root ganglion neurons.
AB  - 1. Calcium currents and transmitter release were studied in cocultures of fetal
      mouse neurons from the ventral half of the spinal cord (VH neurons) and from
      dorsal root ganglion (DRG neurons). The effects of BayK 8644 and omega-conotoxin
      on calcium currents and transmitter release were compared. 2. The presence of low
      voltage-activated (LVA) calcium current in both VH and DRG neurons is variable.
      Some cells exhibit only high voltage-activated (HVA) currents, whereas others
      show both HVA and LVA currents. 3. BayK 8644 did not affect LVA currents but
      strongly augmented both steady and transient components of the HVA calcium
      conductance. 4. omega-Conotoxin GVIA reduces both transient and steady components
      of the HVA but does not abolish either component even after 3 h of application.
      5. Calcium currents that were resistant to omega-contoxin were augmented by BayK
      8644. 6. Synaptic transmission between pairs of spinal cord neurons from the
      ventral half of the spinal cord (VH-VH connections) or between dorsal root
      ganglion neurons and VH neurons (DRG-VH connections) were studied with two-cell
      recording and stimulation techniques. 7. In approximately 70% of VH-VH
      connections and 50% of DRG-VH connections, BayK 8644 or its active optical isomer
      failed to affect transmitter output. Substantial augmentation of the remainder of
      the connections could be reliably produced by the dihydropyridines. Raised
      calcium in the extracellular medium produced augmentation of synaptic connections
      in all cases. BayK 8644 produced substantial, consistent augmentation of voltage
      sensitive calcium channels in both VH and DRG neurons. 8. The toxin, omega
      conotoxin, produced no consistent effect on excitatory or inhibitory postsynaptic
      potentials (EPSPs or IPSPs) elicited in VH neurons by stimulation of nearby VH
      neurons. VH EPSPs elicited by stimulation of nearby DRG neurons were reduced to
      approximately 50% of control values after 10 min of omega-conotoxin perfusion.
      Spontaneous and evoked synaptic activity could be recorded in VH neurons as long
      as 2 h after cultures were incubated in 0.5 microM omega-conotoxin. omega
      Conotoxin produced a modest reduction in HVA currents in both VH and DRG neurons.
      9. BayK 8644 did not produce consistent augmentation of transmission at the frog
      neuromuscular junction. omega-Conotoxin produced total blockade of transmission
      in this preparation. 10. We conclude that neither sustained nor inactivating high
      threshold voltage-sensitive (HVA) calcium channels sensitive to BayK 8644 or
      omega-conotoxin such as those measured in the neuronal cell bodies are
      responsible for action-potential-evoked transmitter release from the majority of
      VH neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374459
TI  - Developmental and neural regulation of a subsarcolemmal component of the rat
      neuromuscular junction.
AB  - We have generated a monoclonal antibody, designated mAb 3G2, which reacts with a
      subsarcolemmal component of the neuromuscular junction in adult rats. mAb 3G2
      immunoreactivity lies beneath and between the ACh receptor-rich synaptic gutters,
      around the sole plate nuclei, and at/near sarcomeric Z-disks in the vicinity of
      the synapse. Localization of mAb 3G2 immunoreactivity to neuromuscular junctions
      begins postnatally and gradually increases to adult levels. The establishment of
      this synaptic localization is neurally regulated, as neonatal denervation
      prevents its occurrence. In adults, denervation results in a loss of synaptic
      immunoreactivity that returns upon reinnervation. The antigen is also found at
      the myotendinous junction; its localization here is innervation independent. mAb
      3G2 recognizes a 41 kDa protein on immunoblots of extracts of newborn muscle.
      Based on its distribution within muscle fibers, its developmental and neural
      regulation, and its molecular weight, the protein recognized by mAb 3G2 can be
      distinguished from other known postsynaptic proteins. Its neural dependence and
      developmental regulation suggest that it may participate in synaptic
      stabilization, perhaps as the intracellular component in a chain of proteins that
      serve to tether the nerve terminal to the perijunctional region of the muscle
      fiber.

PMID- 1374460
TI  - Analysis of cis-regulatory elements in the 5' flanking region of the Drosophila
      melanogaster choline acetyltransferase gene.
AB  - We have analyzed the cis-regulatory elements in the 5' flanking region of the
      Drosophila choline acetyltransferase gene (ChAT, E.C.2.3.1.6). DNA fragments were
      fused to the Escherichia coli lacZ reporter gene and introduced into the
      Drosophila germ line by P-element-mediated transformation. A 7.4 kb 5' flanking
      sequence directed beta-galactosidase expression in the adult optic lobes and
      other well-defined CNS structures with a pattern very similar to the distribution
      of endogenous ChAT protein. In contrast, the proximal 3.3 kb and 1.2 kb of 5'
      flanking DNA directed lacZ expression in only selected subsets of the structures
      seen with the 7.4 kb lacZ construct. Our results indicate that both qualitative
      and quantitative regulatory elements are present in the 5' flanking DNA and that
      these elements distinguish various subsets of cholinergic neurons. We have also
      fused the same 5' flanking DNA sequences to wild-type ChAT cDNA and used these
      constructs to transform Chatsl mutant flies. Not only the 7.4 kb cDNA construct,
      but also the 3.3 and 1.2 kb constructs, rescued Chatsl from temperature-dependent
      paralysis and adult lethality, indicating that the regulatory information in any
      of these genomic fragments can drive sufficient wild-type ChAT expression to
      overcome these mutant phenotypes.

PMID- 1374461
TI  - Neonatal capsaicin treatment attenuates spinal Fos activation and dynorphin gene
      expression following peripheral tissue inflammation and hyperalgesia.
AB  - An animal model of nociception involving unilateral hindpaw inflammation has been
      used to examine behavioral, molecular, and biochemical aspects of well
      characterized spinal cord neural circuits involved in pain transmission. The
      neurotoxin capsaicin administered neonatally was used to modify this neuronal
      system by producing a selective destruction of most small, unmyelinated primary
      afferent axons. Capsaicin had minimal effects on the behavioral hyperalgesia and
      edema associated with the hindpaw inflammation and on the constitutive expression
      of preprodynorphin (PPD) mRNA and preproenkephalin mRNA in the spinal cord.
      However, the inflammation-induced increases in Fos-like immunoreactivity (Fos-LI)
      and in PPD mRNA were greatly attenuated by neonatal capsaicin treatment. The data
      indicate that input from small-diameter unmyelinated primary afferents is
      important for the stimulus-induced increase in Fos-LI and PPD mRNA. Our finding
      that neonatal capsaicin reduces the levels of Fos-LI and PPD mRNA in a related
      fashion in the spinal dorsal horn provides further evidence for a relationship
      between the protein product of the c-fos protooncogene and regulation of
      dynorphin gene transcription.

PMID- 1374462
TI  - Voltage-activated K+ currents in acutely isolated hippocampal astrocytes.
AB  - Hippocampal astrocytes were acutely isolated by papain treatment and mechanical
      trituration. Astrocytes were identified by their distinctive stellate morphology
      and immunocytochemical staining for glial fibrillary acidic protein. The
      electrophysiological properties of these cells were investigated using whole-cell
      voltage-clamp techniques. Three kinetically and pharmacologically distinct
      voltage-activated K+ currents were identified in most cells; they resembled the
      neuronal A-current, delayed rectifier, and inward rectifier. The activation
      threshold of the A-current was -40 mV with a time to peak that ranged from 10
      msec at -20 mV to 6 msec at 100 mV. Steady-state inactivation was observed when
      the holding potential was positive to -100 mV. The current was half-inactivated
      at -60 mV and totally inactivated at -20 mV. The A-current was suppressed by 4
      aminopyridine (4-AP). The delayed rectifier was activated by depolarizing pulses
      more positive than -40 mV and had a half time of activation that ranged from 18
      msec at -20 mV to 10 msec at potentials more positive than 40 mV. This current
      did not inactivate during a 100 msec pulse and was suppressed by extracellular
      tetraethylammonium (TEA). An inwardly rectifying current was elicited by
      hyperpolarizing pulses more negative than -80 mV. This current was not blocked by
      extracellular TEA or 4-AP and was never observed in the presence of external
      Ba2+. Voltage-activated inward Na+ currents were never observed. Voltage
      activated K+ channels may enhance the local K+ spatial buffering capabilities of
      the astrocyte syncytium when extracellular [K+] increases during neuronal
      activity.

PMID- 1374463
TI  - Prostaglandin E2 increases calcium conductance and stimulates release of
      substance P in avian sensory neurons.
AB  - Prostaglandins are known to lower activation threshold to thermal, mechanical,
      and chemical stimulation in small-diameter sensory neurons. Although the
      mechanism of prostaglandin action is unknown, agents known to elevate
      intracellular calcium produce a sensitization that is similar to that produced by
      prostaglandins. Consistent with the idea of prostaglandin-induced elevations in
      calcium, prostaglandins might also stimulate the release of neurotransmitter from
      sensory neurons. We therefore examined whether prostaglandin E2 (PGE2) could
      enhance the release of the putative sensory transmitter substance P (SP) from
      isolated neurons of the avian dorsal root ganglion grown in culture. Utilizing
      the whole-cell patch-clamp recording technique, we also examined whether PGE2
      could alter calcium currents in these cells. Exposure of sensory neurons to PGE2
      produced a dose-dependent increase in the release of SP. One micromolar PGE2
      increased release approximately twofold above basal release, whereas 5 and 10
      microM PGE2 increased release by about fourfold. The release evoked by these
      higher concentrations of PGE2 was similar in magnitude to the release induced by
      50 mM KCl. Neither arachidonic acid (10 microM), prostaglandin F2 alpha (10
      microM), nor the lipoxygenase product leukotriene B4 (1 microM) significantly
      altered SP release. The addition of 1 microM PGE2 increased the peak calcium
      currents by 1.8-fold and 1.4-fold for neurons held at potentials of -60 and -90
      mV, respectively. The action of PGE2 was rapid with facilitation occurring within
      2 min. As with release studies, arachidonic acid, prostaglandin F2 alpha, and
      leukotriene B4 had no significant effect on the amplitude of the calcium current.
      These results suggest that PGE2 can stimulate the release of SP through the
      activation or facilitation of an inward calcium current. The capacity of PGE2 to
      facilitate the calcium current in these sensory neurons may be one mechanism to
      account for the ability of prostaglandins to sensitize sensory neurons to
      physical or chemical stimuli.

PMID- 1374464
TI  - Kindling enhances sensitivity of CA3 hippocampal pyramidal cells to NMDA.
AB  - Kindling is a form of experimental epileptogenesis in which periodic electrical
      stimulation of a brain pathway induces a permanently hyperexcitable state.
      Previous studies suggested that kindling might be explained, at least in part, by
      an increased sensitivity of brain neurons to NMDA receptor agonists. This
      possibility was investigated with the use of grease-gap preparations for assaying
      the depolarizing responses of CA3 and CA1 hippocampal pyramidal cells to amino
      acid excitants. When studied 1-2 months after the last evoked seizure, CA3
      pyramidal cells from kindled rats were five- to sixfold more sensitive to NMDA
      than CA3 pyramidal cells from controls. A similar, though smaller, effect of
      stimulation was observed 1 d after the last evoked seizure. The greater potency
      of NMDA in kindled rats can probably be explained by enhanced expression of NMDA
      receptors in the presence of a receptor reserve. The stimulation protocol did not
      alter the ability of Mg2+ to reduce NMDA potency. It also affected neither the
      response of CA3 pyramidal cells to AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate] nor the response of CA1 pyramidal cells to NMDA or AMPA. In
      area CA3, the potency of NMDA, but not of AMPA, declined 2.5-4-fold over the 1-2
      month experimental period, apparently as a result of increasing age. This age
      related loss of sensitivity to NMDA was completely prevented by kindling. These
      findings suggest that kindling prevents a loss of NMDA receptor function in CA3
      pyramidal cells that normally occurs during early adulthood. Such a change could
      contribute to maintenance of the kindled state.

PMID- 1374465
TI  - Mental development of 2-year-old children exposed to alcohol in utero.
AB  - In a prospective follow-up study, 60 children exposed to alcohol in utero were
      assessed by a psychologist (Bayley Mental scale) and a speech therapist (Reynell
      Verbal Comprehension scale) at a mean age of 27 months. Many mothers had been
      able to reduce their alcohol consumption during pregnancy, so the children could
      be divided into those exposed to heavy drinking during the first trimester only
      (group 1, n = 20), those exposed during the first and second trimesters (group 2,
      n = 20), and those exposed throughout pregnancy (group 3, n = 20). Forty-eight
      nonexposed children were examined to set the -2 SD limit for subnormal
      performance on the Bayley and Reynell tests. No definite effect of alcohol
      exposure on mental or language development was found in group 1. Children in
      group 3 scored significantly lower than children in group 1 both on the Bayley
      Mental scale and on the Reynell Verbal Comprehension scale; delay in language
      development was seen more often in group 2 than in group 1. The diagnosis of
      fetal alcohol syndrome was made in seven children (one in group 2 and six in
      group 3) and the diagnosis of fetal alcohol effects in 13 children (one in group
      1, three in group 2, and nine in group 3). Efforts should be made to identify and
      find proper treatment for women who drink alcohol early in their pregnancies.

PMID- 1374466
TI  - Differentiation of homozygous hemoglobin E from compound heterozygous hemoglobin
      E-beta O-thalassemia by hemoglobin E mutation analysis.
AB  - OBJECTIVES: To facilitate the differential diagnosis of hemoglobin FE in newborn
      infants (homozygous hemoglobin E vs hemoglobin E-beta O-thalassemia). METHODS:
      The beta-globin gene in DNA from infants found to have hemoglobin FE in the
      California newborn screening program was amplified by the polymerase chain
      reaction, and the product was digested with Mnl I, which fails to cut the product
      when the hemoglobin E mutation is present. When both amplified alleles fail to be
      cut, homozygous EE is diagnosed. If only one allele is cut, a beta-globin allele
      without the E mutation is present (non-E), which is most likely a gene with a
      beta O-thalassemia mutation. RESULTS: Samples from 18 infants revealed an EE
      genotype, and from two samples a non-E/E genotype was determined. Clinical
      examination of these two patients confirmed a diagnosis of hemoglobin E-beta O
      thalassemia. An independent clinical diagnosis agreed with DNA analysis for all
      17 of the 20 infants for whom follow-up and family studies were available. The
      DNA results were obtained within a week, but the clinical diagnoses often could
      not be resolved unequivocally for months. CONCLUSIONS: The direct analysis of
      patient DNA samples for the hemoglobin E mutation allowed rapid and accurate
      diagnosis in this sample of infants with hemoglobin FE on the newborn screen.
      This rapid discriminatory test should reduce cost and simplify the diagnostic
      approach for these patients, which currently consists of expensive and lengthy
      follow-up until clinical data and family studies result in a diagnosis.

PMID- 1374467
TI  - Effects of lorazepam tolerance and withdrawal on GABAA receptor-operated chloride
      channels.
AB  - Mice were treated with 4 mg/kg of lorazepam for 7 days via implanted osmotic mini
      pumps. After chronic drug treatment, brains were assayed for GABA-mediated
      chloride flux (GABA-Cl-). Compared to control, brain membranes from lorazepam
      tolerant mice were resistant to flunitrazepam stimulation of GABA-Cl-. Lorazepam
      tolerance did not affect [3H]diazepam binding affinity but did lower binding
      number slightly. Membranes from lorazepam-tolerant mice were cross-tolerant to
      both ethanol and phenobarbital stimulation of GABA-Cl-. Pentobarbital-stimulation
      of GABA-Cl- was equivalent in the two treatment groups. An increase in maximum
      inhibition of chloride flux produced by the benzodiazepine partial inverse
      agonist, n-methyl-beta-carboline-3-carboxamide (FG-7142) in membranes from
      lorazepam-tolerant mice was observed. FG-7142 was also found to be a more potent
      inhibitor of [3H]diazepam binding in membranes from lorazepam-tolerant mice.
      Withdrawal from chronic treatment by an acute injection with the benzodiazepine
      antagonist RO-15-1788 (flumazenil), restored functioning of the channel complex
      to control levels. There were no differences between membranes from control and
      lorazepam withdrawn mice in stimulation by flunitrazepam, ethanol, phenobarbital
      and pentobarbital or inhibition by FG-7142 of GABA-Cl-. [3H]Diazepam-saturated
      binding parameters and inhibition of binding by FG-7142 were similar. Chronic
      administration of lorazepam reduces the coupling between the benzodiazepine
      agonist site and the chloride channel and concomitantly increases coupling
      between the channel and the inverse agonist site. Furthermore, these findings
      offer neurochemical evidence for cross-tolerance to ethanol and phenobarbital
      after induction of lorazepam tolerance.

PMID- 1374468
TI  - Inhibitors of calmodulin impair the constitutive but not the inducible nitric
      oxide synthase activity in the rat aorta.
AB  - The possibility that calmodulin inhibitors impair the constitutive but not the
      inducible nitric oxide synthase(s)-mediated inhibitions of tone was investigated
      in the rat aorta. The endothelium-dependent relaxations evoked by acetylcholine,
      ATP and the calcium ionophore A23187 (which are mediated by the constitutive
      nitric oxide synthase) were inhibited by calmodulin inhibitors [calmidazolium, W
      7 and (N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide, hydrochloride,
      fendiline] and by an inhibitor of nitric oxide synthase, nitro L-arginine. Nitro
      L-arginine but not calmidazolium reduced the inhibitory influence of the
      endothelium on the concentration-contraction curves evoked by phenylephrine.
      Treatment of aortic rings without endothelium with interleukin-1 beta inhibited
      the contractions to phenylephrine by inducing nitric oxide synthase activity.
      Nitro L-arginine but not calmidazolium restored the contractility of the aortic
      rings. The relaxations evoked by a donor of nitric oxide, 3-morpholino
      sydnonimine, were minimally affected by calmidazolium and nitro L-arginine. The
      basal tissue content in, and the production of, guanosine 3',5' cyclic
      monophosphate evoked by acetylcholine in rings with endothelium were inhibited by
      calmidazolium and nitro L-arginine. The production of cyclic GMP evoked by
      interleukin-1 beta in rings without endothelium was inhibited by nitro L-arginine
      but not by calmidazolium. These observations indicate that calmodulin inhibitors
      inhibit the constitutive but not the inducible nitric oxide synthase(s) in the
      rat aorta.

PMID- 1374469
TI  - Effect of flunarizine and nimodipine on the decrease in tryptophan hydroxylase
      activity induced by methamphetamine and 3,4-methylenedioxymethamphetamine.
AB  - The effect of calcium channel blockers on the decrease in central tryptophan
      hydroxylase (TPH) activity and serotonin (5-HT) concentration induced by repeated
      large doses of methamphetamine (METH) or 3,4-methylenedioxymethamphetamine (MDMA)
      was evaluated. Rats received four or five injections of METH (10 or 15 mg/kg) or
      MDMA (10 mg/kg) at 6-h intervals, and were sacrificed 18 to 20 h or 1 week after
      the last administration. Flunarizine (30 mg/kg) prevented the decline in cortical
      and neostriatal TPH activity induced by MDMA, but failed to alter the effect of
      METH. The effect of flunarizine on the METH- and MDMA-induced changes in cortical
      5-HT and 5-hydroxyindoleacetic acid concentrations paralleled the changes in
      enzyme activity. Nimodipine, diltiazem or TA-3090 failed to prevent the MDMA- and
      the METH-induced decline in TPH activity or in 5-HT and 5-hydroxyindoleacetic
      acid content. Because haloperidol failed to mimic the protective action of
      flunarizine, it is unlikely that flunarizine exerts its action by blocking the
      dopamine D-2 receptors. This study suggests that calcium influx may participate
      in the MDMA-induced decline in central TPH activity, and that the mechanism by
      which MDMA and METH decreases TPH activity differs.

PMID- 1374471
TI  - Involvement of dynorphin A and not substance P in the spinal antianalgesic action
      of capsaicin against morphine-induced antinociception in mice.
AB  - In previous publications we proposed that dynorphin A (1-17) (Dyn) functions as
      an antianalgesic agent in the spinal cord of mice. Whether endogenously released
      or administered directly to the spinal cord, this antianalgesic action attenuates
      the antinociceptive effect of morphine (Mor) in the mouse tail-flick test.
      Because this action of Dyn in the spinal cord appeared to be congruous with the
      function of substance P (SP), experiments were designed to compare the actions of
      the two on Mor-induced antinociception. Inhibition of the tail-flick response
      induced by i.c.v. administration of Mor was attenuated by intrathecal (i.t.)
      administration of SP or Dyn. This antianalgesic effect of Dyn (5 fmol) but not SP
      (74 pmol) was antagonized by naloxone and nor-binaltorphimine administered i.t.
      Capsaicin (Cap) i.t. at a 0.1-microgram dose, like SP and Dyn, antagonized the
      antinociceptive effect of Mor given i.c.v. Excellent evidence exists to indicate
      that, in rats, Cap (30-70 micrograms i.t.) releases SP in the spinal cord and
      that Mor inhibits this release. Present experiments indicated, however, that i.t.
      administration of low doses of Cap (0.05-0.5 microgram) in mice preferentially
      released Dyn and not SP as based on the following results. 1) The antianalgesic
      action of Cap i.t. against Mor i.c.v. was antagonized by naloxone and nor
      binaltorphimine i.t. as was Dyn i.t. (but not SP i.t.). 2) A SP antagonist, (D
      Pro2, D-Phe7, D-Trp9)-SP, did not reverse the effect of Cap or Dyn given i.t.,
      even though it antagonized the effect of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374470
TI  - Lasting effects of (+-)-3,4-methylenedioxymethamphetamine (MDMA) on central
      serotonergic neurons in nonhuman primates: neurochemical observations.
AB  - The purpose of this study was to assess the duration of (+-)-3,4
      methylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons
      in nonhuman primates. Fifteen squirrel monkeys were used: three served as
      controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4
      consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug
      treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were
      examined for regional brain content of serotonin and 5-hydroxyindoleacetic acid,
      and for the number of [3H] paroxetine-labeled serotonin uptake sites. Two weeks
      after MDMA treatment, monkeys showed profound reductions in all three
      serotonergic presynaptic markers. By 10 weeks, there was evidence of partial
      recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal
      cortex). However, by 18 months, it was evident that recovery did not continue, as
      serotonergic deficits returned to the level of severity observed 2 weeks after
      MDMA treatment. This was the case in all brain regions examined except the
      thalamus and hypothalamus. In the thalamus, the level of serotonin increased to
      63% of control, whereas that of 5-hydroxyindoleacetic acid recovered completely.
      In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid
      were 140 and 187% of control, respectively. These results suggest that MDMA
      produces lasting effects on serotonergic neurons in nonhuman primates, with most
      brain regions showing evidence of persistent denervation and some showing signs
      of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The
      morphological and functional correlates of these enduring neurochemical changes
      in the MDMA-treated primate remain to be delineated.

PMID- 1374472
TI  - Evidence that carbamazepine and antiepilepsirine may produce a component of their
      anticonvulsant effects by activating serotonergic neurons in genetically epilepsy
      prone rats.
AB  - In order to investigate the mechanism of action of anticonvulsant drugs, we
      examined the effects of carbamazepine (CBZ) and antiepilepsirine (AE) on
      convulsions and on brain biogenic amines in genetically epilepsy-prone rats
      (GEPR). AE was an effective anticonvulsant in moderate seizure GEPR (GEPR-3, ED50
      = 65.5 mg/kg) and in severe seizure GEPR (GEPR-9, ED50 = 68.5 mg/kg). Because
      GEPR are known to have deficiencies in brain norepinephrine (NE) and serotonin (5
      HT), which are of etiologic significance in their seizure predisposition, we
      evaluated the effects of anticonvulsant doses of CBZ and AE on dialyzable NE, 5
      HT and their metabolites. Dialysis probes were stereotaxically inserted into
      hippocampi of awake and unrestrained GEPR-3 and GEPR-9. Either AE (100 mg/kg in
      GEPR-3; 100 mg/kg in GEPR-9) or CBZ (45 mg/kg in GEPR-3; 6 mg/kg in GEPR-9) was
      administered i.p. after establishing basal release. Significant increases in
      dialyzable 5-HT, but not NE, were seen at the approximate time to peak
      anticonvulsant effect for each drug in both strains. The changes in 5-HT release
      remained closely associated with the anticonvulsant actions after i.v.
      administration of either AE (40 mg/kg) or CBZ (25 mg/kg) in GEPR-3. Pretreatment
      of GEPR-9 with p-chlorophenylalanine depleted brain 5-HT and greatly diminished
      the anticonvulsant effectiveness of both drugs. We conclude that both CBZ and AE
      are effective anticonvulsants in GEPR and that enhancement of serotonergic
      transmission may contribute to the anticonvulsant effect of these drugs.

PMID- 1374473
TI  - Liarozole, an inhibitor of retinoic acid metabolism, exerts retinoid-mimetic
      effects in vivo.
AB  - Liarozole is an imidazole-containing compound that inhibits the cytochrome P-450
      dependent metabolism of all-trans-retinoic acid (RA). In vitro, liarozole (IC50,
      2.2 microM) suppressed the P-450-mediated conversion of RA to more polar
      metabolites by hamster liver microsomes. In vivo, it enhanced the plasma level of
      RA from mostly undetectable values (less than 0.5 ng/ml) in control rats to 1.4
      +/- 0.1 and 2.9 +/- 0.1 ng/ml in animals treated p.o. with 5 and 20 mg/kg of
      liarozole, respectively. Moreover, liarozole possessed antikeratinizing activity:
      when dosed subchronically (5-20 mg/kg, once daily for 3 days) to ovariectomized
      rats, the compound reversed the vaginal keratinization induced in these animals
      by estrogenic stimulation. Dose response experiments indicated that the
      antikeratinizating effect of liarozole was as potent as that of RA. One
      dimensional electrophoresis and immunoblotting of extracted vaginal epithelia
      showed that liarozole shared with RA the ability to inhibit the synthesis of high
      molecular weight (57-60 kDa) keratin proteins, and to enhance the expression of
      the 45 to 47 kDa keratin polypeptides. Furthermore, we found that
      antikeratinizing doses of liarozole doubled the RA concentration in the vagina of
      ovariectomized rats: the mean amount of RA extracted from 200 mg of vaginal
      tissue was increased from 1.1 +/- 0.1 ng in vehicle-treated animals to 2.2 +/-
      0.2 and 2.6 +/- 0.2 ng after treatment with 5 and 20 mg/kg of liarozole,
      respectively. These findings indicate that liarozole, an inhibitor of RA
      metabolism and RA produce similar morphologic and biochemical effects on the
      differentiation process of rat vaginal epithelium.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1374474
TI  - Positive LE preps and negative ANA in brothers with SLE: is there still a role
      for the LE cell prep? A literature review.

PMID- 1374475
TI  - Nerve growth factor-stimulated calcium uptake into PC12 cells: uniqueness of the
      channel and evidence for phosphorylation.
AB  - Nerve growth factor stimulates the uptake of radioactive calcium into PC12 cells.
      This stimulation is inhibited by low concentrations of dideoxyforskolin or
      staurosporine, and by high concentrations of nifedipine or cadmium. On the other
      hand, neither dideoxyforskolin nor staurosporine inhibited the stimulation of
      calcium uptake caused by BK-8644 or adenosine triphosphate (ATP). Nickel
      inhibited only the effect of ATP on calcium uptake, and actually stimulated the
      effects of either BK-8644 or nerve growth factor. Down-regulation of L-calcium
      channels by BK-8644 blocked the subsequent stimulation of calcium uptake by this
      agent, but not the stimulation by nerve growth factor. Conversely, pre-treatment
      of the cells with nerve growth factor inhibited the subsequent stimulation of
      calcium uptake by nerve growth factor, but not the stimulation by BK-8644. The
      effects of BK-8644 and nerve growth factor on calcium uptake were additive, as
      were the effects of nerve growth factor and ATP. Phosphatase 2A inhibited the
      effect of nerve growth factor on calcium uptake, but did not influence the action
      of BK-8644. On the other hand, calcineurin inhibited the effect of BK-8644 on
      calcium uptake, but potentiated the action of nerve growth factor. Calmidazolium
      or fluphenazine also inhibited the effect of nerve growth factor on calcium
      uptake, but okadaic acid stimulated it. A comparison of the effects of these
      inhibitors on the actions of various calcium channel agonists shows that the
      channels on which the action of nerve growth factor is exerted are different than
      either the L-type calcium channels or the ATP-activated calcium
      channels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374476
TI  - Expression of the neu proto-oncogene by Schwann cells during peripheral nerve
      development and Wallerian degeneration.
AB  - The neu gene, which encodes a putative tyrosine kinase growth factor receptor
      termed p185neu, was originally identified as a dominant transforming gene in
      neurogliomas and schwannomas induced by transplacental treatment of rat embryos
      with ethylnitrosourea. The present studies were undertaken to determine the
      expression pattern of the neu gene in peripheral nerve. Northern blot analysis of
      total RNA isolated from rat sciatic nerves demonstrated prominent neu mRNA
      expression on postnatal days 1 and 7, with substantially lower expression up to
      adulthood. Immunohistochemical studies confirmed expression of p185neu by Schwann
      cells (SC) in developing sciatic nerve and minimal p185neu immunoreactivity in
      adult nerves. However, neu mRNA and p185neu protein progressively increased
      following sciatic nerve transection in adult animals. In addition, neu mRNA and
      p185neu were found in neonatal rat sciatic nerve SC and several SC-derived cell
      lines. In resting SC, neu mRNA was expressed at a low level, but was greatly
      increased by treatment with forskolin and glial growth factor. These studies
      demonstrate that the neu gene and its protein product, p185neu, are expressed by
      SC both in vivo and in vitro and suggest that p185neu plays a role in the
      regulation of SC proliferation or differentiation.

PMID- 1374477
TI  - Differentiation of PC12 cells with nerve growth factor is associated with
      induction of transin synthesis and release.
AB  - We have identified and characterized a calcium-dependent metalloproteinase which
      is induced in rat pheochromocytoma cells (PC12 cells) during differentiation with
      nerve growth factor (NGF). Assays of proteolytic activity in media from
      differentiated PC12 cell cultures revealed a NGF-dependent increase in the
      activity of a proteinase which has a molecular weight of 62 kDa. Studies using
      serine, thiol, and metalloproteinase inhibitors demonstrated that the secreted
      enzyme is a metalloproteinase. Treatment of culture supernatants with
      aminophenylmercuric acid (APMA), a known activator of metalloproteinases,
      resulted in a decrease in the molecular weight of the proteinase. Western blot
      analysis of culture media from NGF-treated PC12 cells using an antibody directed
      against a synthetic peptide of rat transin identified this metalloproteinase as
      transin. Treatment of PC12 cells with acidic and basic fibroblast growth factor
      (FGF) resulted in distinct morphological changes as well as transin release.
      Incubation with epidermal growth factor (EGF) did not induce transin release.
      Dexamethasone inhibited the induction of transin release by NGF. 35S-methionine
      labeling and immunoprecipitation of newly synthesized proteins from culture
      supernatants confirmed that NGF induced the synthesis of this enzyme 8 hr after
      NGF treatment. The NGF-dependent induction of transin, a calcium-dependent
      metalloproteinase which degrades type IV collagen, laminin, and fibronectin
      suggests that transin may function to degrade the surrounding extracellular
      matrix during the invasive process of axonal elongation in neuronal development
      thereby allowing the movement of growth cones and axons toward specific targets.

PMID- 1374478
TI  - Inhibition of nerve growth factor-stimulated neurite outgrowth by methylamine
      modified alpha 2-macroglobulin.
AB  - alpha 2-Macroglobulin (alpha 2M) is a rather ubiquitous protein in extracellular
      spaces of mammals. It is an inhibitor of endopeptidases, can be modified by
      aliphatic amines, and combines with a number of hormones/cytokines such as beta
      nerve growth factor (NGF) [Koo PH, Stach RW (1989): J Neurosci Res 22:247]. The
      objective of this study is to compare the NGF-binding properties of methylamine
      modified human alpha 2M (MA-alpha 2M) versus normal alpha 2M and their effects on
      the biological activity of NGF and neurite extension by embryonic chicken dorsal
      root ganglia. As determined by gel filtration, polyacrylamide gel
      electrophoresis, and equilibrium binding studies, these two forms of alpha 2M are
      similar in their binding affinities, with MA-alpha 2M binding about twice as much
      NGF as normal alpha 2M. Both normal alpha 2M and MA-alpha 2M combine
      noncovalently with NGF, and prior modification of alpha 2M is unnecessary for the
      binding to occur. In contrast to normal alpha 2M, MA-alpha 2M potently inhibits
      the biological activity of NGF and exerts a dose-dependent inhibition on the NGF
      stimulated neurite outgrowth by embryonic chicken dorsal root ganglia in culture.
      The inhibitory effect of MA-alpha 2M can be overcome by higher NGF
      concentrations, but is irreversible at lower NGF concentrations. Trypsin-modified
      alpha 2M combines covalently and noncovalently with more NGF than normal alpha 2M
      but has very little neurite inhibitory activity. The mechanism of inhibition by
      MA-alpha 2M is discussed.

PMID- 1374479
TI  - Purified cultures of keratin-positive olfactory epithelial cells: identification
      of a subset as neuronal supporting (sustentacular) cells.
AB  - The mammalian olfactory neuroepithelium, lining part of the nasal cavity, retains
      into adulthood progenitor cells for the olfactory receptor neurons and other cell
      types in the epithelium. The details of cellular lineage relationships are not
      completely understood. In particular, the exact nature of the interactions
      between several progenitor cell types and their relationship to neurons is not
      known. Studies of this system have been hampered by the lack of cell culture
      models and insufficient cell-type-specific markers. Antibodies to the
      cytokeratins are fairly specific markers for one potential progenitor cell type,
      the dark basal cells of the olfactory epithelium. Keratin immunostaining was used
      to develop cell culture systems which contained large numbers of putative dark
      basal cells, using the soft nasal mucosal tissues of both newborn and adult rats.
      Media and substrate conditions were optimized. The conditions which supported
      growth of keratin-positive nasal cells for greater than one month, and allowed
      partial purification, suggested similarities between olfactory and skin
      keratinocytes. Immunostaining with a monoclonal antibody specific for
      sustentacular cells (SUS-1) showed a subset of these cells present in culture,
      with some cells double-labelled with anti-keratin. This staining confirms the
      olfactory origin of at least a subset of the cells, and supports the proposal
      that the majority of cells were the dark olfactory basal cells. This culture
      system gives novel insights into olfactory epithelial cell physiology, and allows
      culture of these cells for further studies examining regulation of
      differentiation.

PMID- 1374480
TI  - Novel antigenic determinant expressed in neurons of the dorsolateral hypothalamus
      in rat and human.
AB  - Previous studies have identified a group of cells in the dorsolateral
      hypothalamus that project to many different areas in the CNS, such as thalamus,
      diagonal band of Broca, basal ganglia, cerebral cortex, hippocampus, and
      olfactory bulb. Their role is presently unknown, but the cells have been reported
      to stain for an intriguing array of putative neurotransmitter-related substances,
      including alpha-melanocyte-stimulating hormone (alpha MSH), melanin-concentrating
      hormone (MCH), human growth-hormone-releasing factor 1-37 (hGRF 1-37),
      corticotropin-releasing factor (CRF), metorphamide, and acetylcholine esterase. A
      monoclonal antibody produced in the present study, alpha C11, stains both the
      cell bodies of this system in hypothalamus, with a punctate pattern, and varicose
      fibers in the various target areas. In double-label immunocytochemical
      experiments in rat DLH, alpha C11 and MCH staining exactly overlaps.
      Concentrations of alpha MSH and MCH high enough to completely block staining with
      the corresponding antisera had no effect on staining with alpha C11. Similarly,
      CRF, hGRF 1-37, and metorphamide were unable to block alpha C11 staining. The
      results suggest that the antigenic epitope for alpha C11 is not contained in
      alpha MSH, MCH, CRF, hGRF, or metorphamide, and thus, that alpha C11 is detecting
      another antigen uniquely expressed in these neurons. The punctate appearance of
      staining in the hypothalamus and the concentration of staining in fiber
      varicosities suggests that the alpha C11 epitope may be involved in synaptic
      function.

PMID- 1374481
TI  - Isolation and characterization of neonatal Schwann cells from cryopreserved rat
      sciatic nerves.
AB  - Much of our knowledge about the development and maintenance of the peripheral
      nervous system has been learned through studying the interaction of neurons, or
      their isolated membranes, with Schwann cells (SC), in tissue culture. Numerous
      approaches have been employed to obtain an adequate quantity of SC, but all have
      been limited by either the uncertainty of obtaining a sufficient amount of
      starting material, the time and expertise required to isolate the SC, or by the
      limited number of SC that can be generated. We have developed a procedure to
      isolate SC from cryopreserved sciatic nerves. This procedure allows for sciatic
      nerves to be pooled until adequate numbers of nerves are obtained, yet still
      produces cells that retain the functional abilities of SC isolated from fresh
      nerves. Sciatic nerves were isolated from 2 day old rat pups, placed in either
      DME media and used fresh or placed in a freezing solution containing DME media
      (25%), DMSO (25%), fetal calf serum (50%), frozen at -70 degrees C and stored in
      liquid nitrogen. The frozen nerves were rapidly thawed to 37 degrees C and single
      cells were prepared from both fresh and frozen nerves using enzymatic and
      mechanical disruption as previously described (Brockes et al., Brain Res 165: 105
      118, 1979). Comparable cell yields were obtained for SC isolated from both frozen
      and fresh nerves. Immunohistochemical staining of both fresh and frozen SC
      produced similar staining patterns with antibodies to GFAP, laminin, CNPase,
      S100, MBP, and P0 protein. Addition of axolemmal enriched membrane fractions to
      both the frozen and fresh SC gave a similar dose response curve of 3H-thymidine
      incorporation, with SC from frozen sciatic nerves responding even better than
      fresh sciatic nerves at higher doses (50 micrograms and 100 micrograms of
      protein/ml). As demonstrated by the cell yield, immunohistochemical staining and
      responses to axolemmal mitogens, this procedure produces SC from frozen sciatic
      nerves with similar characteristics to those isolated from fresh nerves. This
      procedure will allow the production and utilization of a large number of SC,
      which will be critical in further studies on the development and maintenance of
      the peripheral nervous system.

PMID- 1374482
TI  - Retinoic acid-regulated expression of proteolipid protein and myelin-associated
      glycoprotein genes in C6 glioma cells.
AB  - The effect of retinoic acid (RA) on the expression of myelin-specific genes,
      i.e., proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) in rat
      glioma C6 cells, was analyzed by Northern blot hybridization. RA-treatment
      increased the steady-state level of the PLP-specific messages within one day
      after RA administration and the upregulation reached a maximum on the third day.
      Concomitantly, the expression of MAG-specific messages in the RA-treated C6 cells
      dropped below the detectability limit. The expression of the PLP gene was
      directly related to the RA concentration increasing to approximately 44-fold over
      the control (untreated cells) level at 10(-6) M RA. The stimulatory effect was
      vitiated by cycloheximide indicating the involvement of intermediate genes in the
      PLP gene activation. The total cellular RNA content and the level of cyclophilin
      mRNA was not changed by the RA-treatment. The present data indicate that RA can
      be a potent modulator of the myelin-specific gene expression. Furthermore, the
      reciprocal response of PLP versus MAG genes to RA demonstrates that these two
      genes utilize different regulatory mechanisms.

PMID- 1374483
TI  - Use of the linked reverse transcription/polymerase chain reaction (RT/PCR) for
      mRNA phenotyping of vascular wall cells.

PMID- 1374484
TI  - Analysis of the ELAM-1 and VCAM-1 promoters--tools to target gene expression in
      endothelium in transgenic animals.

PMID- 1374485
TI  - [Clinical and cytological features of CD7 positive biphenotypic leukemias].
AB  - Clinical and cytological features of CD7 positive acute leukemias with
      biphenotypic characteristics in childhood were documented. From 87 patients with
      CD7+ acute leukemias, nine patients were selected on the basis of the
      biphenotypic expression of T-lymphoid and myelomonocytic antigens. The blasts of
      these patients expressed cell surface CD7, cytoplasmic CD3 and cytoplasmic CD13.
      In addition to these antigens, surface CD13 was also expressed after short term
      culture without any mitogens or stimulators. The double PAP method for detecting
      cytoplasmic antigens (CD3, CD13, beta F1, delta TCS1) was employed in this study.
      The average age of these patients was higher (10.2 y/o) than patients with common
      ALL. Mediastinal masses were observed in 4 of 9 patients. They were treated
      according to the diagnoses based on conventional hematological methods and
      surface antigen expression. In all 9 patients, complete remission was achieved,
      however, early relapse was noticed in 7. This study suggests that the leukemia
      cells of these patients may be derived at an early stage during the
      differentiation of multipotential hematopoietic stem cells. New therapeutic
      approaches are necessary to improve the outcome of such T/M biphenotypic
      leukemias.

PMID- 1374486
TI  - [Anorexia nervosa with neutropenia--response of neutrophils to G-CSF].
AB  - A 50-year-old woman with anorexia nervosa was admitted for evaluation of
      neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid
      cells had decreased. Homogeneous substance deposited in the marrow, stained by
      alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM
      were decreased in number and myeloid pool in the bone marrow also decreased. Anti
      neutrophilic antibody was negative. Neutropenia may be related to myeloid
      hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells
      in the bone marrow under long-term mal-nutritional state. Neutrophils markedly
      increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without
      the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is
      effective to administer G-CSF to anorexia nervosa with neutropenia.

PMID- 1374487
TI  - [Induction of complete remission in a case of drug-resistant childhood acute
      megakaryoblastic leukemia by combination of G-CSF and chemotherapy].
AB  - In a 4-year-old girl having acute megakaryoblastic leukemia, recombinant human
      granulocyte colony-stimulating factor (G-CSF) was used in combination with
      chemotherapy for remission induction after the second relapse of her leukemia. G
      CSF was given intravenously at a dose of 100 micrograms/m2/day 24 hours prior to
      chemotherapy until the peripheral neutrophil counts fully recovered. Cytosine
      arabinoside (Ara-c) [100mg/m2/day] and VP-16 [100mg/m2/day] were given from day 1
      through day 10. Her leukemia was resistant to chemotherapy alone after the second
      relapse but complete remission and hematological recovery were achieved two
      months after the start of this therapy. Although in vitro clonal assay did not
      show significant stimulation of colony formation by G-CSF on leukemia cells of
      this patient, and the mechanism underlying remission induction by this
      combination therapy remains unclear, it may be of benefit to use G-CSF in
      combination with chemotherapy for patients with drug-resistant leukemia.

PMID- 1374488
TI  - [Arrhythmias, excitation and conduction abnormalities in chronic kidney failure
      with hemodialysis].

PMID- 1374489
TI  - [Unresectable tumors of the periampullar zone].

PMID- 1374490
TI  - [Incidence of postoperative bacterial infections after planned intraocular
      interventions].
AB  - Between August 1982 and August 1984 3059 intraocular operations were performed
      with topical prophylactic antibiotics. Results of conjunctival cultures did not
      influence the surgical schedule. 8179 intraocular operations were performed
      between September 1984 and August 1988. An intraocular operation was postponed
      until conjunctival cultures were negative using topical antibiotics administered
      at hourly intervals. The rate of postoperative intraocular infections decreased
      significantly (p less than 0.0001) from 21 (0.69%) of 3059 during the first to 9
      (0.11%) of 8179 intraocular operations during the second observation period. In
      the first period 11 vitrectomies and 2 enucleations due to bacterial
      endophthalmitis had to be performed. In the second period 2 vitrectomies and no
      enucleations were necessary (p less than 0.0001). Our results indicate, that
      decontamination of the conjunctiva may be an import factor for the prevention of
      postoperative endophthalmitis following elective intraocular surgery.

PMID- 1374491
TI  - A method for reliable and permanent intracellular staining of retinal ganglion
      cells.
AB  - We have developed a method for reliable, permanent, high-resolution intracellular
      staining of ganglion cells in mammalian retinas. Living ganglion cells in the
      isolated retina are impaled in vitro and injected intracellularly with both
      Lucifer Yellow (LY) and biocytin. After fixation and aggressive pretreatment of
      the retina with detergents, the LY is tagged immunohistochemically with biotin
      using a commercially available anti-LY antibody and a biotinylated secondary
      antibody. A conventional avidin-biotin procedure is then used to visualize both
      the biocytin and the biotinylated bridge antibody, yielding complete Golgi-like
      filling of the soma, dendrites and axon. Advantages of the method include the
      ease and speed of dye injection, the reliable recovery of stained cells, the
      large number of cells which can be stained in single retinas, and the high
      resolution and permanence of the stain, which permit prolonged examination and
      quantitative analysis.

PMID- 1374493
TI  - Intensive sequential chemotherapy for children with acute myelogenous leukemia:
      VAPA, 80-035, and HI-C-Daze.
AB  - Between 1976 and 1988 we treated 228 children age 18 years or less with AML on
      three consecutive protocols: Vapa, 80-035 and Hi-C Daze. All three protocols used
      intensive consolidation chemotherapy. VAPA and 80-035 used an anthracycline with
      standard dose cytosine arabinoside (ara-c) for remission induction followed by
      twelve to fourteen months of intensive sequential chemotherapy. Results were
      similar for these two treatment protocols. 90/125 (72%) of the patients achieved
      a complete remission with 45% projected disease free survival for the complete
      responders, and an event free survival of 31%. 8/26 (VAPA) and 3/21 (80-035)
      relapses were primary CNS. No factor significantly influenced the rate of
      complete remission, but M4 and M5 FAB subtypes and WBC greater than 100,000/ul
      predicted for shorter remission duration. 103 children received Hi-C DAZE. The
      protocol differed by utilizing high-dose ara-c during induction and consolidation
      and pairing VP-16 with azacytidine. Hi-C DAZE was modified after the first 33
      patients (group 1) because of CNS toxicity; VP-16/azacytidine were substituted
      for high dose ara-c/daunorubicin as the second induction course for the next 70
      patients (group 2). Twenty eight of 33 (85%) of group 1 and 54/70 (77%) of group
      2 entered remission.

PMID- 1374492
TI  - Current strategies for treatment of acute myeloid leukemia at St Jude Children's
      Research Hospital.
AB  - We examined the feasibility of maintaining specific plasma concentrations of ara
      C and VP-16 in children with AML. Sixty-one children were treated with 6
      sequential cycles of intensive chemotherapy consisting of: (1) cytarabine (ara
      C)/VP-16, (2) ara-C/daunorubicin (Dauno), (3) VP-16/amsacrine (m-AMSA), (4) VP
      16/5-azacytidine (5-Az), (5) ara-C/Dauno, and (6) ara-C/VP-16. Fifty-nine
      children had de novo AML, and 2 had a previous myelodysplastic syndrome. The
      number of patients with each specific FAB subtype was: M0-1; M1-7; M2-24; M3-7;
      M4-5; M5-11; and M7-6. Simultaneous continuous infusions of ara-C and VP-16
      (cycle 1) given at individualized doses to achieve drug plasma concentrations of
      1 microM and 30 microM, respectively, produced complete remission (CR) in 26 of
      61 patients (43%); an additional 17 patients entered CR after Dauno/ara-C (cycle
      2), and one patient required 4 cycles of chemotherapy to achieve CR (total CR
      rate = 72%). The preliminary 2-year event-free survival (EFS) for patients with
      FAB-M1 and -M2 AML was only 15% versus 40% for those with FAB-M4 and -M5 AML.
      Overall, 21 of the 61 patients remain in CR (2-yr EFS = 29%). We conclude that
      intense treatment with ara-C and VP-16 at doses individualized to achieve target
      plasma concentrations is feasible although severely myelosuppressive. It results
      in an acceptable CR rate, but does not improve EFS.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1374494
TI  - [Early mental disorders are underlying causes of severe juvenile delinquency-
      increased research activities are necessary].

PMID- 1374495
TI  - [Follow-up of leukemia in drivers is of interest].

PMID- 1374496
TI  - Release of serotonin only in painful area during cluster headache attacks.

PMID- 1374497
TI  - The effects of different hexachlorocyclohexanes and cyclodienes on glucose uptake
      and inositol phospholipid synthesis in rat brain cortex.
AB  - The inositol lipids from rat brain miniprisms were deacylated and separated by
      anion-exchange chromatography in order to determine whether or not gamma
      hexachlorocyclohexane (gamma-HCH, lindane) and related compounds affect the
      different phosphatidylinositols. The incorporation of myo-[2-3H]inositol into
      phosphatidylinositol, phosphatidylinositol monophosphate and phosphatidylinositol
      bisphosphate were inhibited by lindane and its delta-HCH isomer. The inhibitory
      effects on phosphatidylinositol synthesis are not prominent in alpha-HCH and they
      are not significant with the beta-HCH and cyclodienes. The results presented here
      indicate that the inhibitory effect of lindane and delta-HCH on the
      phosphatidylinositol metabolism was no exclusively due to an interference with
      glucose transport. Lindane-treated miniprisms showed decreased myo-[2-3H]inositol
      uptake and, proportionately, an even greater inhibition of inositol phospholipid
      synthesis. Cellular uptake can, therefore, not account for all of the lindane
      inhibition.

PMID- 1374498
TI  - Nuclear mechanisms mediate rhythmic changes in vasopressin mRNA expression in the
      rat suprachiasmatic nucleus.
AB  - Vasopressin (VP) gene expression in the rat suprachiasmatic nucleus (SCN) is
      subject to a cyclical mode of regulation which is indicative of a close
      association with the circadian clock intrinsic to this area of the hypothalamus.
      Previous studies show that both the amount and size (due to differential
      polyadenylation) of VP mRNA are reduced during the dark phase of the daily cycle.
      We have now identified the cellular site wherein these changes are mediated. By
      transcriptional run-on analysis of nuclei isolated at different time points from
      the SCN we have shown that an attenuation of transcriptional activity can account
      for the dark-phase reduction in VP mRNA levels; by comparison with other genes
      expressed in this tissue, a significant, VP gene-specific reduction was observed
      which resulted in dark-phase transcriptional activity at 30% of light-phase
      activity (P less than 0.005). A similar diurnal variation was not found in the
      supraoptic nucleus. In addition, by Northern analysis of sub-cellular RNA pools,
      we have demonstrated that the smaller, dark-phase-specific VP RNA species is
      located, in abundance, within the nuclear fraction. These results provide clear
      evidence that the cyclical changes in SCN VP mRNA expression are primarily
      regulated within the nucleus, indicating that any potential regulation in the
      cytoplasm is of secondary importance. Further analysis of the molecular
      components which mediate the cyclical changes in transcriptional activity of the
      VP gene may identify fundamental aspects of neuronal timing mechanisms.

PMID- 1374499
TI  - Differential regulation in the avian song control circuit of an mRNA predicting a
      highly conserved protein related to protein kinase C and the bcr oncogene.
AB  - An RNA identified by differential cDNA cloning (HAT-2) is highly enriched in
      canary forebrain in areas associated with the control of complex learned
      behaviors and higher perceptual processes. The nucleotide sequence predicts a
      protein that is 96% identical to the product of the n-chimaerin gene isolated
      from human brain and contains two identifiable domains suggesting a novel role in
      signal transduction processes. One domain is similar to the sequence in protein
      kinase C which mediates diacylglycerol binding and regulation. The second domain
      is similar to a portion of BCR, a GTPase-activating protein encoded by the
      breakpoint cluster region gene. In male canaries examined during the song season,
      HAT-2 RNA shows variable expression within the song control circuit, and is
      notably less abundant in the three nuclei which concentrate androgens (HVC, RA
      and L-MAN). A fundamental function in the vertebrate forebrain and a possible
      role in the regulation of neural plasticity are suggested by the conserved
      structure and pattern of expression of this gene in the brain.

PMID- 1374500
TI  - In vivo modulation of myelin gene expression by human recombinant IL-2.
AB  - We treated adult mice with human recombinant interleukin-2 (IL-2) and determined
      the expression of the genes encoding for the major central and peripheral myelin
      proteins. In the CNS, myelin basic protein (MBP) and myelin-associated
      glycoprotein (MAG) mRNA levels were the same both in IL-2-treated and in control
      mice. Proteolipid protein (PLP) transcript was decreased in IL-2-treated animals
      when compared to controls. In the PNS, the messages for the glycoprotein P0 and
      for MBP were markedly increased in IL-2-treated animals when compared to
      controls.

PMID- 1374501
TI  - Age-related variations in relative abundance of alternative spliced D2 receptor
      mRNAs in brain areas of two rat strains.
AB  - Age-related reduction in the steady-state levels of messenger RNA for D2(415) and
      D2(444), the alternatively spliced form of dopamine D2 receptors, was observed in
      different rat brain areas using the sensitive reverse transcription (RT)
      polymerase chain reaction (PCR) technique. In both Sprague-Dawley and Wistar aged
      rats, the decrease was more pronounced in the D2(444) isoform mRNA thus leading
      to a changed ratio in striatum as well as in the hippocampus.

PMID- 1374502
TI  - Messenger RNAs coding for receptors and channels in the cerebral cortex of adult
      and aged rats.
AB  - Poly(A)+ mRNAs from the cerebral cortex of aged (24 months) and young adult (3
      months) rats were isolated and injected into Xenopus oocytes to express
      functional neurotransmitter receptors and voltage-operated channels.
      Electrophysiological recordings of induced membrane currents were used as a
      measure of the relative amounts of mRNA encoding different receptors and
      channels, and to study their functional properties. There were no large
      differences apparent between mRNAs from aged and adult rats, in marked contrast
      to the dramatic (1000-fold) changes in mRNA expression that occur during
      embryonic and postnatal development. The membrane currents induced by glutamate
      or acetylcholine (ACh) application were roughly one third smaller in oocytes
      injected with mRNA from aged cerebral cortex than in oocytes injected with mRNA
      from adult cerebral cortex, whereas currents induced by gamma-aminobutyric acid
      (GABA), kainate or serotonin (5-HT) application, and by activation of voltage
      operated Na+ and Ca2+ channels were not significantly different. We did not
      observe any age-related differences in the properties of the receptors and
      channels studied.

PMID- 1374503
TI  - Temperature-dependent blockade of nucleocytoplasmic transport of newly
      synthesized RNA in neurons.
AB  - This study evaluates the temperature sensitivity of transport of recently
      synthesized RNA from the nucleus to the cytoplasm (nucleocytoplasmic transport)
      in CNS neurons. Rat hippocampal slices were incubated with [3H]uridine for 1 h to
      label recently synthesized RNA. Slices were then fixed immediately or maintained
      at 27 degrees C or 37 degrees C for chase intervals of 3, 4.5, and 6 h to allow
      for nucleocytoplasmic transport of recently synthesized RNA. The time-dependent
      translocation of recently synthesized RNA was evaluated autoradiographically. At
      the end of the 1 h pulse at either 27 degrees C or 37 degrees C, the label was
      localized exclusively over nuclei. In slices maintained at 37 degrees C, labeling
      expanded to cover the cell body and proximal dendrites. However, in slices that
      were labeled and maintained at room temperature, labeling remained confined to
      the nucleus. In slices that were pulse-labeled at room temperature, and then
      transferred to 37 degrees C medium, cytoplasmic labeling increased as a function
      of time. Nucleocytoplasmic transport of RNA in cultured rat hippocampal neurons
      showed a comparable temperature sensitivity. The inhibition of nucleocytoplasmic
      transport of RNA at room temperature provides an opportunity to evaluate neuronal
      function when no new RNA molecules can reach the cytoplasm.

PMID- 1374504
TI  - Cocaine self-administration differentially alters mRNA expression of striatal
      peptides.
AB  - The influence of cocaine self-administration on the expression of messenger RNAs
      for dynorphin, enkephalin and substance P was analyzed in the rat striatum with
      in situ hybridization histochemistry. Cocaine, an indirect dopamine agonist, was
      found to differentially affect the levels of mRNA encoding these neuropeptides in
      different subregions of the striatum. Following a 7 day period of variable free
      access to cocaine, dynorphin and substance P mRNA levels were elevated throughout
      the striatum, but the increases were substantially greater in the dorsal striatum
      than in the nucleus accumbens. Enkephalin mRNA was not significantly altered in
      the dorsal striatum but was slightly elevated in the nucleus accumbens. These
      results suggest that cocaine self-administration has differential effects on
      striatonigral and striatopallidal projection neurons, and that these effects vary
      in subregions of the striatum.

PMID- 1374505
TI  - Characterisation of the L- and N-type calcium channels in differentiated SH-SY5Y
      neuroblastoma cells: calcium imaging and single channel recording.
AB  - We have used single cell imaging of [Ca2+]i and single channel cell-attached
      patch clamp recording to characterise the Ca2+ channels present on the plasma
      membrane of retinoic acid-differentiated human neuroblastoma (SH-SY5Y) cells.
      Exposure to raised K+ (45 or 60 mM) for 1 min resulted in a transient rise in
      [Ca2+]i which was abolished by cadmium (100 microM). The amplitude of the evoked
      rise varied from cell to cell. Both omega-Conus toxin (500 nM) and nifedipine (10
      microM) reduced, but did not abolish, the rise in [Ca2+]i whereas Bay K 8644 (3
      microM) potentiated it. In single channel records both L- and N-type Ca2+ channel
      openings were observed during membrane depolarisations from a holding potential
      of -90 mV. L-type channel openings (unitary conductance 22.5 pS) were prolonged
      by S(+)-PN 202-791 (500 nM) and could still be evoked from a depolarised holding
      potential (-40 mV). N-type channel openings (unitary conductance 12.5 pS) were
      unaffected by the dihydropyridine agonist but were inactivated at a holding
      potential of -40 mV. These results indicate that, in contrast to previous
      observations using whole cell recording, retinoic acid-differentiated SH-SY5Y
      cells express both L- and N-type Ca2+ channels.

PMID- 1374507
TI  - Transcriptional regulation of neuromodulin (GAP-43) in mouse neuroblastoma clone
      N1E-115 as evaluated by the RT/PCR method.
AB  - The steady-state level of the neuromodulin transcript in the neuron-like N1E-115
      cell line was measured with a method combining reverse transcription and the
      polymerase chain reaction (RT/PCR). Total RNA was isolated from N1E-115 cells and
      treated with DNAse to remove residual DNA; cDNA was synthesized from this RNA by
      priming with random hexamers. For PCR amplification, primers for neuromodulin
      were designed for regions of the coding sequence that were identical in mouse,
      rat, and human. In one approach (the 'ratio method'), variations in RNA yield and
      cDNA synthesis efficiency were controlled for by amplifying a reference
      (housekeeping) gene (glyceraldehyde phosphate dehydrogenase; GAPDH). To control
      for inter-experimental variations in PCR amplification efficiencies the data were
      analyzed on semi-logarithmic plots, with which the relative levels of the
      starting templates could be determined by extrapolating the plots to cycle number
      zero (0). In another approach with RT/PCR (the 'spiking method'), the absolute
      level of N1E-115 neuromodulin cDNA was assessed by adding known amounts of cloned
      human neuromodulin template to the RT/PCR assay of N1E-115 nucleic acid and
      comparing the increased yield of product across cycles. When the spike was added
      at either the cDNA level (in the form of double-stranded DNA) or at the total RNA
      level (as sense RNA), the levels of N1E-115 calculated were virtually the same:
      509 fg and 495 fg of coding region per ug total RNA in confluent N1E-115 cells,
      respectively. Treatment of N1E-115 cells with 2% dimethylsulfoxide for three days
      elevated neuromodulin mRNA levels 5.6-fold. Conversely, treatment of N1E-115
      cells with 100 nM phorbol myristate acetate for 24 h decreased the level of
      neuromodulin mRNA by 70%. Under carefully controlled conditions and within
      certain limits of precision, the RT/PCR method appears to be suitable for
      assessing the level of low abundance mRNA under various pharmacologically-induced
      conditions.

PMID- 1374506
TI  - Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain
      neurons after neurotoxin lesioning: a model for neuron aging.
AB  - Slow neuron regression develops during the adult phase of life in select brain
      systems of mammals. We describe a model in adult rats that resolves several
      phases in a slow atrophic process that differentially influences levels of mRNA
      and protein for tyrosine hydroxylase (TH). Responses of striatal dopaminergic
      markers to 6-hydroxydopamine (6-OHDA) lesions in rats indicated that the striatal
      terminals maintained TH protein, despite greater than 3-fold loss of TH mRNA in
      the substantia nigra pars compacta (SNC) cell bodies whose axons project to the
      striatum. The loss of TH mRNA/cell was progressive up to 9 months, whereas SNC
      cell body shrinkage stabilized by 3 months post-lesioning. Consideration of
      possible mechanisms in protein turnover motivated a search for PEST motifs in the
      TH of rats and other vertebrates that could be a point of regulation by altering
      the rate of TH protein turnover.

PMID- 1374509
TI  - DNA amplification.

PMID- 1374508
TI  - Production and analysis of specific monoclonal antibodies against the cell wall
      of Mycobacterium avium.
AB  - Monoclonal antibodies (mAbs) against Mycobacterium avium were produced which
      specifically reacted with cell walls of M. avium. The binding pattern was not
      limited to one subtype. The three most specific mAbs showed binding to the outer
      surface of M. avium but not to other mycobacterial or bacterial cell surfaces.
      The combined results of enzyme-linked immunosorbent assay, immunoblot and dot
      blot showed that mAb 4A006 bound to an epitope located in the cell wall and on
      the cell surface and mAb 4A010 to an epitope exposed on the cell surface and the
      cytoplasm. The mAb 4A009-binding epitope was only detectable on the cell surface
      but not in the cell wall or cytoplasmic fractions of M. avium. In the immunoblot
      technic a protein antigen with a molecular mass of 27-29 kDa was identified by
      the mAbs. The mAb 4A006 reacted with 142 out of 143 M. avium subtypes 1, 4 and 8
      obtained from AIDS patients. These mAbs seem to be applicable for the
      identification of M. avium complex after culture.

PMID- 1374510
TI  - Gene amplification; what are we learning?

PMID- 1374511
TI  - From amplification to function: the case of the MDR1 gene.
AB  - This review describes the features of gene amplification associated with the
      selection of multidrug-resistant cell lines. Some of these lines carry multiple
      copies of the MDR1 gene that encodes P-glycoprotein, a broad specificity efflux
      pump. The MDR1 gene was initially identified as the common component of the
      amplicons found in multidrug-resistant cell lines selected with different drugs.
      Subsequent studies have established that increased MDR1 expression is sufficient
      for the multidrug-resistant phenotype. MDR1-containing amplicons may include a
      number of additional transcribed genes that do not appear to contribute to
      multidrug resistance. MDR1 amplification is associated with specific chromosomal
      changes and apparently non-random recombinational events. Increased expression of
      the MDR1 gene, however, does not necessarily require gene amplification. Although
      amplification of the MDR1 gene has not been found in clinical tumor samples,
      increased expression of this gene is commonly observed in different types of
      cancer and appears to be a significant marker of clinical drug resistance.

PMID- 1374512
TI  - Regularities of karyotypic evolution during stepwise amplification of genes
      determining drug resistance.
AB  - Analysis of chromosomal alterations during stepwise development of mdr1, dhfr, or
      CAD gene amplifications in a large number of independently selected Djungarian
      hamster DM-15 and murine P388 sublines revealed typical patterns of karyotypic
      evolution, specific for multiplication of each of these genes in each cell type.
      Some principal similarities of karyotypic evolution were noted in at least two
      different systems. They include: (i) appearance at the first selection step of a
      new chromosomal arm bearing the resident gene copy followed at the next selection
      steps by the formation in these specific chromosomal arms of amplified DNA tandem
      arrays; (ii) translocations of amplified DNA from its initial site to other, also
      non-random, chromosomal sites; and (iii) emergence in the cell variants with high
      degrees of gene amplification of multiple extra-chromosomal elements. The most
      prominent distinctions among the systems were as follows: (i) different
      structures, evidently containing amplified DNAs, appeared at the initial steps of
      amplification of different genes--additional heterogeneously staining regions in
      specific chromosomal segments in the case of amplification of dhfr or CAD genes
      in DM-15 cells, and mini-chromosomes in the case of mdr1 gene amplification in
      both DM-15 and P380 cells; (ii) distinct patterns of location of the amplified
      mdr1 gene copies are characteristic of Djungarian hamster DM-15 and murine P388
      cell derivatives after subsequent steps of selection--at the site of resident
      gene localization or in some other, also non-random, chromosomal sites in DM-15
      sublines, and predominantly extra-chromosomal in P388 sublines. We propose that
      different mechanisms are responsible for the initial steps of amplification of
      dhfr and CAD genes on the one hand and the mdr1 gene on the other: non-equal
      sister-chromatid exchanges and autonomous replication of the extra-chromosomal
      elements. It seems, however, that both mechanisms may be involved in further
      rounds of amplification of each of these three genes.

PMID- 1374513
TI  - Amplification of the dihydrofolate reductase gene in methotrexate-resistant
      Chinese hamster cells.

PMID- 1374514
TI  - Induction of gene amplification by 5-aza-2'-deoxycytidine.
AB  - Treatment of Syrian hamster kidney cells with the demethylating agent 5-aza-2'
      deoxycytidine (azadC) increased both the frequency and the rate of gene
      amplification appreciably. AzadC caused substantial DNA demethylation, which is
      likely to be responsible. The magnitude of the increases depended on the
      concentrations of both azadC and the drug used for selection. A transient stress
      response is not responsible since the increases were not dependent on
      cytotoxicity and were still apparent after several weeks. We discuss mechanisms
      by which azadC treatment may induce amplification by rendering DNA more prone to
      this process or by increasing the transcription of genes whose protein products
      stimulate amplification.

PMID- 1374515
TI  - Molecular dissection of mammalian gene amplification: new mechanistic insights
      revealed by analyses of very early events.

PMID- 1374516
TI  - A branching process model of gene amplification following chromosome breakage.
AB  - We have devised a mathematical model of gene amplification utilizing recent
      experimental observations concerning dihydrofolate reductase (DHFR) gene
      amplification in CHO cells. The mathematical model, based on a biological model
      which proposes that acentric elements are the initial intermediates in gene
      amplification, includes the following features: (1) initiation of amplification
      by chromosomal breakage to produce an acentric structure; (2) replication of
      acentric DNA, once per cell cycle; (3) dissociation of replicated acentric DNA;
      (4) unequal segregation of acentric DNA fragments to daughter cells at mitosis;
      (5) subsequent reintegration of acentric fragments into chromosomes. These
      processes are assumed to be independent for each element present in a cell at a
      given time. Thus, processes of unequal segregation and integration may occur in
      parallel, not necessarily in a unique sequence, and may be reiterated in one or
      multiple cell cycles. These events are described mathematically as a Galton
      Watson branching process with denumerable infinity of object types. This
      mathematical model qualitatively and quantitatively reproduces the major elements
      of the dynamical behavior of DHFR genes observed experimentally. The agreement
      between the mathematical model and the experimental data lends credence to the
      biological model proposed by Windle et al. (1991), including the importance of
      chromosome breakage and subsequent gene deletion resulting from resection of the
      broken chromosome ends as initial events in gene amplification.

PMID- 1374517
TI  - Gene amplification in a human osteosarcoma cell line results in the persistence
      of the original chromosome and the formation of translocation chromosomes.
AB  - Although gene amplification, a process that is markedly enhanced in tumor cells,
      has been studied in many different cell systems, there is still controversy about
      the mechanism(s) involved in this process. It is still unclear what happens to
      the DNA sequences that become amplified, whether they remain present at their
      original location (conservative gene amplification) or whether gene amplification
      necessarily results in a deletion at the original location (non-conservative gene
      amplification). We have studied gene amplification in a human osteosarcoma cell
      line, starting from a cell clone which contains only one copy of a plasmid
      integrate. Independent amplificants, originating from this clone and containing
      elevated plasmid copy numbers, were isolated and analyzed. Based on previous
      observations, encompassing the persistence of single-copy DNA sequences besides
      amplified DNA sequences clustered at a different location in the independent
      amplificants, we proposed an amplification pathway including a local duplication
      step and transposition of the duplicated DNA to other chromosomal positions. Now
      we have extended our study to more independent amplificants. We prove that the
      single-copy plasmid-containing chromosomes in the different amplificants and the
      single-copy plasmid-containing chromosome in the original parental cell clone are
      indeed identical, namely a translocation chromosome composed of at least three
      parts of which two originate from chromosomes 14 and 17. We show that the unit of
      amplification and the unit of the proposed transposition event are at least 1.5
      Mb. We also demonstrate that the amplified DNA sequences, present at genomic
      locations other than the original single-copy DNA sequences, are preferentially
      associated with chromosome 16. We find that the amplified DNA sequences are often
      located at or near a site of chromosome translocation involving chromosome 16. In
      one cell clone we detect the amplified DNA sequences in most of the cells to be
      located within a complete chromosome 16 while in a minority of cells the
      amplified sequences are located at or near a breakpoint on a translocation
      chromosome 16. This indicates that this amplification region is highly unstable
      and frequently gives rise to translocation events.

PMID- 1374518
TI  - The evolution of the amplified adenylate deaminase 2 domains in Chinese hamster
      cells suggests the sequential operation of different mechanisms of DNA
      amplification.
AB  - Fluorescent in situ hybridization was used to localize the adenylate deaminase 2
      (AMPD2) genes and flanking sequences on the chromosomes of the Chinese hamster
      line GMA32 and to study the distribution of additional copies of these genetic
      sequences in amplified mutants selected at several early stages of the
      amplification process. The synteny of AMPD2 genes and MDR1 genes, located on
      chromosomes 1, was demonstrated; in GMA32 the existence of a rearrangement
      positioning the two AMPD2 genes at different distances from the telomeres was
      disclosed. Using this structural marker, we showed that the amplified copies
      distribute along only one of the chromosomes 1. Their organization in different
      cells of clonal mutant populations at a very early stage of amplification was
      extremely heterogeneous; classes of organization could be recognized however.
      Their quantitative distribution at this stage and in cells which went through 10
      more division cycles suggests an evolution pathway common to the mutant clones
      under study: as a rule, tandems of few units of identical and very large size (47
      Mb) appear to be the first detected product of amplification; this organization
      is progressively overtaken by structures with more units of reduced and irregular
      size, while, in a growing number of cells, clusters of much shorter units can be
      observed. The nature of segregative amplification mechanisms operating in these
      processes and the possible involvement of replicative ones are discussed.

PMID- 1374519
TI  - In vivo gene amplification in non-cancerous cells: cholinesterase genes and
      oncogenes amplify in thrombocytopenia associated with lupus erythematosus.
AB  - The ACHE and BCHE genes, encoding the acetylcholine hydrolysing enzymes
      acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE), co-amplify with
      several oncogenes in leukemic patients with platelet deficiency
      (thrombocytopenia). This and other experiments implicated ACHE and BCHE in the
      development of bone marrow megakaryocytes, the progenitors of platelets.
      Therefore, we wished to find out whether cholinesterase gene amplification would
      also occur in non-cancerous platelet disorders and, if so, whether oncogenes
      would amplify in such cases as well. The autoimmune disease systemic lupus
      erythematosus (SLE) presents an appropriate model system for this issue, since
      patients with SLE may suffer from thrombocytopenia resistant to most treatment
      modalities. Here, we report a 40-80-fold amplification of genomic sequences from
      the ACHE and BCHE genes as well as the C-raf, V-sis and C-fes/fps oncogenes in
      peripheral blood cells from an SLE patient with severe thrombocytopenia. PvuII
      restriction analysis and DNA blot hybridization of the amplified ACHE and BCHE
      sequences demonstrated apparent aberrations in both genes, suggesting that
      malfunctioning of modified, partially amplified cholinesterase genes may be
      involved in the etiology of thrombocytopenia associated with SLE. These
      observations imply that cholinergic mechanisms regulate megakaryocytopoiesis,
      shed new light on the diverse hematologic findings characteristic of SLE, and may
      become valuable as diagnostic, treatment and prognostic tools in the follow-up of
      patients suffering from thrombocytopenia associated with SLE. Furthermore, these
      findings reinforce the notion that cholinesterase gene amplifications are
      causally related with platelet abnormalities in multiple hemopoietic disorders.

PMID- 1374520
TI  - Gene amplification in the murine SEWA system.
AB  - Considerable work with DNA amplification has been carried out in the murine SEWA
      ascites tumor cell system. In SEWA cells there is 'spontaneous' amplification of
      the c-myc oncogene, and transitions between different cytogenetic expressions of
      gene amplification such as DM (double minutes), CM (C-bandless chromosomes) and
      HSR (homogeneously staining regions) of the amplified DNA have been recorded
      during serial in vivo transplantations. In SEWA cells it has also been shown that
      the c-myc-containing DM will he lost under in vitro conditions, but are rapidly
      recovered if the cells are reinjected into animals. Additional gene amplification
      has been superimposed on the c-myc amplification in SEWA cells by stepwise
      selection in vitro, leading to resistance to different drugs, such as
      methotrexate, actinomycin D, colcemid and vincristine. Cytogenetically, DNA
      amplification is multifaceted and, in addition to the structures mentioned, it
      may also take the form of CB (chromatin bodies), which have been shown to be the
      carriers of resistance genes in hybrids between multidrug-resistant SEWA cells
      and Chinese hamster CHO cells. In most instances, DM are noncentromeric and
      distributed by a 'hitch-hiking' mechanism at mitosis; in one colcemid-resistant
      SEWA line, however, we have shown that the DM carry active centromeres. The
      molecular mechanism behind DNA amplification appears to be complex. We have shown
      that in four independently derived multidrug-resistant SEWA sublines the
      amplicons resided on circular molecules which were about 2500 kb long and carried
      at least five genes, including the three mouse mdr genes. Within the circles the
      DNA was unrearranged compared to the organization of the DNA in sensitive cells.

PMID- 1374521
TI  - Amplification of the N-myc gene in human neuroblastomas: tandemly repeated
      amplicons within homogeneously staining regions on different chromosomes with the
      retention of single copy gene at the resident site.

PMID- 1374522
TI  - Amplified cellular oncogenes in neoplasms of the human central nervous system.
AB  - Significant advances have recently been made in a number of areas concerning
      central nervous system (CNS) neoplasia. Particularly salient are the following:
      (1) gene amplification is related to increasing grade of human glioma malignancy
      and occurs in approximately 40% of the most common and most malignant variety of
      glioma, glioblastoma multiforme (GBM), (2) by far the most commonly amplified
      gene in glioblastomas is the epidermal growth factor receptor (EGFR) gene, which
      is amplified in about one third of GBMs, (3) a small percentage of GBMs amplify N
      myc or the novel sequence gli, (4) the EGFR gene is rearranged in at least half
      of gliomas in which it is amplified, and (5) EGFR gene rearrangement results in
      external domain deletions that yield truncated EGF receptors. Antibodies specific
      for the mutant EGF receptor fusion junction have been successfully produced and
      provide stimulating new potential avenues for tumor imaging and therapy. For
      pediatric CNS neoplasms, only medulloblastoma has been investigated in adequate
      numbers; a small percentage exhibit amplification of either the N-myc or c-myc
      genes.

PMID- 1374523
TI  - Amplification and rearrangement of L-myc in human small-cell lung cancer.
AB  - DNA amplification of cellular proto-oncogenes is a well-established and common
      mechanism of oncogene activation in several types of human tumors, including the
      rapidly fatal small-cell lung cancer (SCLC). Approximately one fourth of primary
      SCLC tumors contain amplified copies of one of the three myc proto-oncogenes.
      Occasionally DNA amplification of the myc genes is associated with DNA
      rearrangements. Specifically, a novel locus named rlf is often involved in
      intrachromosomal L-myc rearrangements in SCLC. The structurally similar
      rearrangements are probably due to a highly repetitive region upstream of the L
      myc gene, and result in the formation of a chimeric rlf-L-myc fusion protein. The
      consistent finding of the rlf-L-myc rearrangement in SCLC suggests that it may
      provide a selective advantage to the cells harboring it.

PMID- 1374524
TI  - DNA amplification at 11q13 in human cancer: from complexity to perplexity.

PMID- 1374525
TI  - DNA sequences amplified in cancer cells: an interface between tumor biology and
      human genome analysis.
AB  - There is growing evidence that amplification of specific genes is associated with
      tumor progression. While several proto-oncogenes are known to be activated by
      amplification, it is clear that not all the genes involved in DNA amplification
      in human tumors have been discovered. Our approach to the identification of such
      genes is based on the 'reverse genetics' methodology. Anonymous amplified DNA
      fragments are cloned by virtue of their amplification in a given tumor. These
      sequences are mapped in the normal genome and hence define a new genetic locus.
      The amplified domain is isolated by long-range cloning and analyzed along three
      lines of investigation: new genes are sought that can explain the biological
      significance of the amplification; the structure of the domain is studied in
      normal cells and in the amplification unit in the cancer cell; attempts are made
      to identify molecular probes of diagnostic value within the amplified domain.
      This application of genome technology to cancer biology is demonstrated in our
      study of a new genomic domain at chromosome 10q26 which is amplified specifically
      in human gastric carcinomas.

PMID- 1374526
TI  - The mechanism of carcinogen-induced DNA amplification: in vivo and in vitro
      studies.
AB  - Exposure to chemical carcinogens provides a means for the enhancement of the
      frequency of gene amplification and for the facilitation of research into its
      mechanism(s). Using carcinogen-induced SV40 amplification as a model system it
      was shown that amplification of the viral sequences occurs via a replication
      dependent mode. This process involves overactivation of the origin region and the
      generation of inverted repeats. Carcinogen-induced enhancement of gene
      amplification is triggered by cellular factors that could act in trans. An in
      vitro amplification system, based on extracts from carcinogen-treated cells and
      SV40 template sequences, was used to further characterize the amplification
      intermediates. The major products of overreplication in this system consist of
      sequences derived from the origin region. Our studies suggest that the ability to
      overreplicate the origin region in vitro derives from the combined action of
      carcinogen-induced factors that trigger overinitiation, with the inherent
      inability of Chinese hamster cell extracts to fully replicate large plasmid
      templates. The newly replicated sequences are not associated with the parental
      molecule and contain hairpin or stem and loop structures. Based on these findings
      we propose a novel replicative mechanism for DNA amplification that allows the de
      novo formation of hairpin structures. According to this model, an obstruction of
      the replication fork may cause an overturning of the DNA polymerase, followed by
      a template switch that leads to the use of the newly replicated strand as a
      template. This mode of replication results in the generation of hairpin
      structures which can function as precursors for the duplicated inverted repeats
      which are commonly observed in amplified genomes. This model is supported by our
      in vitro and in vivo studies. The relevance of this model for the amplification
      of cellular sequences is discussed.

PMID- 1374527
TI  - Mutagenicity of substituted anthraquinones in the Ames/Salmonella microsome
      system.
AB  - Unsubstituted anthraquinone, 4 substituted anthraquinones (emodin, danthron,
      physcion, a new compound M-108-C) and 3 dimers (skyrin, rugulosin, rugulin) were
      tested using the Ames/Salmonella assay (strains TA98, TA100, TA1537 and TA102).
      Danthron and emodin were found to be mutagenic for TA1537 with or without
      metabolic activation, physcion only with metabolic activation. A significant
      difference was found between the mutagenic activities of emodin (16.2 His+/nmole)
      and danthron (6.5 His+/nmole) as well as a high specific mutagenic activity for
      physcion (11.6 His+/nmole). These results on structure-mutagenic activity
      relationships suggest that the 6-methyl group plays an important role in the
      mutagenic activity after metabolic activation. Furthermore, and contrary to
      emodin, physcion exhibited a weak mutagenic activity for TA102, probably due to
      the formation of a different metabolite. Such information is necessary to
      evaluate the potential carcinogenic hazard of these compounds.

PMID- 1374528
TI  - Farm-grade chlorpyrifos (Durmet) is genotoxic in somatic and germ-line cells of
      Drosophila.
AB  - The mutagenic potential of Durmet, a farm-grade formulation of chlorpyrifos, was
      studied in the Drosophila wing mosaic and sex-linked recessive lethal tests.
      Larvae of the 2nd or 3rd instar carrying suitable recessive genetic markers on
      chromosome 3 were exposed to different concentrations of the insecticide and the
      frequency of induction of mutant mosaic spots on the wings was noted. The Basc
      technique was followed to study the induction of sex-linked recessive lethals. On
      the basis of the frequency of induction of mosaic wing spots and sex-linked
      recessive lethals, it is concluded that Durmet is genotoxic in somatic cells as
      well as germ cells of Drosophila.

PMID- 1374529
TI  - The genotoxicity of the anti-cancer drug mitoxantrone in somatic and germ cells
      of Drosophila melanogaster.
AB  - The novel antineoplastic drug mitoxantrone was studied for its genotoxic effects
      in Drosophila melanogaster. In male germ cells, the clinical preparation
      Novantrone, the dihydrochloride salt of mitoxantrone, did not induce sex-linked
      recessive lethal mutations in feeding and injection experiments with adult flies,
      although statistically the results were inconclusive rather than truly negative.
      However, the free base mitoxantrone was weakly, but significantly genotoxic in
      this test (0.14% lethals/mM exposure concentration); this is most probably the
      result of prolonged exposure. On the other hand, both forms of mitoxantrone
      assayed were clearly genotoxic in the somatic mutation and recombination test of
      the wing. This test assays the cells of the proliferating imaginal wing discs of
      larvae. Depending on the feeding method used, the overall clone induction
      frequency was in the range of about 2-6 x 10(-5) per cell and cell generation and
      per mM exposure dose. Correction of these frequencies according to mean clone
      size led to slightly higher estimates (by about 5-25% higher). Although the
      majority of the clone induction events are due to mitotic recombination, a
      significant proportion can be attributed to mutational events (gene and
      chromosome mutations). The genotoxicity of mitoxantrone seems to depend mainly on
      impaired DNA synthesis in cycling cells owing to the compound's ability to
      inhibit topoisomerase II by intercalation into DNA.

PMID- 1374530
TI  - Antimutagenic effect of eight natural foods on moldy foods in a high liver cancer
      incidence area.
AB  - Ames test procedures were used to test 8 natural food extracts for their
      antimutagenic activity against the mutagenic activity induced in S. typhimurium
      strains TA98 and TA100 by aflatoxin B1 (AFB1) or metabolic extracts from A.
      versicolor or A. ochraceus. The tested substances were extracted repeatedly with
      acetone. The revertants induced by AFB1, metabolic extracts of A. versicolor or
      A. ochraceus were significantly decreased when extracts of the 8 natural foods
      were added to the media. The results showed that these extracts had marked
      inhibitory effects on the mutagenic activity induced by AFB1 or metabolic
      extracts of the two molds and also suggested that antimutagenic substances were
      present in these natural foods. These experiments provide a scientific basis for
      the study of food substances for the prevention of carcinogenesis. It is
      considered that these 8 natural food extracts produce marked antimutagenic
      effects and are practically valuable in the field of chemoprophylaxis of liver
      cancer in humans.

PMID- 1374531
TI  - Comparison of chemically induced chromosome loss in a diploid, triploid, and
      tetraploid strain of Saccharomyces cerevisiae.
AB  - Triploid and tetraploid strains of Saccharomyces cerevisiae were constructed and
      the spontaneous loss during mitosis of one, two or three copies of chromosome VII
      was determined. In one strain, a triploid (VM2) in which expression of the
      recessive alleles can be observed only after loss of two copies of chromosome VII
      (3N-2), the spontaneous frequency of chromosome loss was lower than in the
      diploid D61.M. In another strain, a tetraploid (VM4) that also requires the loss
      of two copies of chromosome VII for observation (4N-2) of the recessive alleles,
      the spontaneous frequency was slightly higher than in the diploid D61.M. The
      spontaneous frequency of other genetic events (that is, mutation, recombination
      or chromosome breakage) were lower by 2-3 orders of magnitude than in the diploid
      strain D61.M. Induction of chromosome loss and other genetic events by
      nocodazole, ethyl acetate, hydroxyurea and ethyl methanesulfonate was determined
      in D61.M, VM2, and VM4, and the results were compared. Nocodazole and ethyl
      acetate induced chromosome loss in both the triploid and the tetraploid strains
      at lower concentrations than required in the diploid. These compounds also
      induced elevated frequencies of other genetic events in both the triploid and the
      tetraploid strains but not in the diploid. Hydroxyurea induced elevated
      frequencies of chromosome loss in the diploid and the tetraploid. Frequencies of
      chromosome loss in the triploid treated with hydroxyurea, although elevated, are
      based on observation of very few colonies of the correct phenotype. Ethyl
      methanesulfonate failed to induce chromosome loss in any of the three strains.
      Hydroxyurea and ethyl methanesulfonate did, however, induce very high frequencies
      of other genetic events.

PMID- 1374532
TI  - The protective effect of 4-[(2-oxo-3-bornylidene)methyl]-phenyl trimethylammonium
      methylsulphate against the induction of gene mutations by ultraviolet, visible
      light and 8-methoxypsoralen in Saccharomyces cerevisiae.

PMID- 1374533
TI  - Micronucleus induction and phagocytosis in mammalian cells treated with diesel
      emission particles.
AB  - Micronucleus induction and phagocytosis in V79 and CHO cells treated with diesel
      emission particles (DEP) were studied. After separation of the sample into
      supernatant and sediment fractions, the genotoxic activity of DEP was shown to
      reside in the supernatant fraction for the DMSO-extracted sample, and in the
      sedimented fraction for the dipalmitoyl lecithin (DPL), a primary component of
      pulmonary surfactant, dispersed sample. More particles from DMSO sediment samples
      were phagocytized than DPL sediment by both types of cells. This had no effect,
      however, on micronucleus induction. CHO cells phagocytized fewer particles, but
      gave a higher number of micronuclei than V79 cells. CHO cells seem to be more
      sensitive to DEP. Evidently, micronucleus induction is not the result of
      phagocytosis per se, but is due to the different response of the indicator cells
      to the DEP sample tested. These results further indicate that most, if not all,
      genotoxic compounds associated with DEP can be extracted by DMSO and that
      genotoxic activity associated with DEP inhaled into the lung may also be
      expressed by dispersion of particles in pulmonary surfactant.

PMID- 1374534
TI  - Mutagenic activity of a series of synthetic and naturally occurring heterocyclic
      amines in Salmonella.
AB  - 26 synthetic and naturally occurring heterocyclic amines were tested in the
      Salmonella/microsome assay (Ames test) using tester strains TA98 and TA100 in the
      presence of an Aroclor-induced rat-liver S9 fraction. 9 of the compounds were
      protein-pyrolysis products which had previously been shown to be mutagenic.
      Mutagenic potencies similar to previously reported values were demonstrated for
      these compounds with the exception that Trp-P-1 was only mutagenic in strain TA98
      in our study, although it had previously been reported to be weakly mutagenic in
      strain TA100. 17 structurally diverse heterocyclic amines were synthesized and
      tested for mutagenicity. The structural diversity of these synthetic heterocyclic
      amines will enhance the sensitivity of future quantitative structure-activity
      relationship (QSAR) studies by demonstrating the structural characteristics
      essential for mutagenicity. The results of this study provide a large data base
      for the mutagenicity of this important class of compounds.

PMID- 1374535
TI  - Importance of the type of soil for the induction of micronuclei and the growth of
      primary roots of Vicia faba treated with the herbicides atrazine, glyphosate and
      maleic hydrazide.
AB  - Research was carried out on the genotoxic effects (induction of micronucleated
      cells in primary root tips) and toxic effects (reduction in primary root growth)
      in young plants of Vicia faba grown in soils with different organic matter
      contents and treated with the herbicides atrazine, glyphosate and maleic
      hydrazide. The data obtained show that the genotoxic effects are noticeably
      influenced by the interactions between the herbicide and the type of soil in
      which the Vicia faba have grown. While maleic hydrazide proved to be highly
      clastogenic for young plants grown in both soils, atrazine was genotoxic only in
      young plants grown in soil poor in organic matter. Glyphosate did not induce
      micronuclei under either soil condition, but induced a significant toxic effect.

PMID- 1374536
TI  - [New approaches in speech therapy].
AB  - Following a brief introduction of the neurological basis and the localization of
      aphasias, we discuss approaches to language therapy which are based on linguistic
      theories. We first sketch principles of language-based therapy. Then we introduce
      communicative aphasia treatment and explain aspects under which the latter
      represents an extension of the language-based approach. In order to provide
      neurological arguments in favour of communicative therapy, we discuss the
      language theory of Hughlings Jackson. Finally, we give examples for communicative
      therapy paradigms, for some of which implementation in specific computer training
      programs is available.

PMID- 1374537
TI  - Neurons in the rat medulla oblongata containing neuropeptide Y-, angiotensin II-,
      or galanin-like immunoreactivity project to the parabrachial nucleus.
AB  - Projections from the medulla to the parabrachial complex of the rat were examined
      for their content of neuropeptide Y-, angiotensin II- or galanin-like
      immunoreactivity using combined retrograde tracing and immunohistochemical
      techniques. Rhodamine-labelled latex microspheres were stereotaxically injected
      into discrete nuclei of the parabrachial complex. After survival of two to five
      days, colchicine (100 micrograms in 10 microliters saline) was injected into the
      cisterna magna. One day later, rats were perfused and the brainstems were
      prepared for visualization of the retrograde tracer and immunoreactivity of one
      of the three peptides. Retrograde labelling verified that the area postrema,
      nucleus of the tractus solitarius, caudal spinal nucleus of the trigeminal nerve,
      parvocellular reticular nucleus, and ventrolateral medulla including the rostral
      ventrolateral medulla and nucleus paragigantocellularis project to the lateral
      parabrachial and Kolliker-Fuse nuclei. While most projections were primarily
      ipsilateral, a small proportion of the projections from the ventrolateral medulla
      was bilateral. Neurons containing neuropeptide Y-like immunoreactivity were found
      in the caudal and intermediate nucleus of the tractus solitarius, dorsal to the
      lateral reticular nucleus and in the nucleus paragigantocellularis. After
      bilateral microsphere injections into the lateral parabrachial and Kolliker-Fuse
      nuclei, double-labelled neurons were found dorsal to the lateral reticular
      nucleus of caudal and intermediate medullary levels, at the ventral surface of
      the medulla at intermediate levels and in the nucleus paragigantocellularis at
      rostral levels. Neurons with angiotensin II-like immunoreactivity were observed
      at the dorsomedial border of the caudal and intermediate nucleus of the tractus
      solitarius, in the area postrema and in the lateral reticular nucleus and nucleus
      paragigantocellularis. Of these neurons, small numbers in the nucleus of the
      tractus solitarius and ventrolateral medulla also projected to the lateral
      parabrachial and Kolliker-Fuse nuclei. Neurons containing galanin-like
      immunoreactivity were found in the caudal nucleus of the tractus solitarius, the
      area postrema, the spinal trigeminal nucleus, the raphe nuclei (pallidus and
      obscurus), the nucleus paragigantocellularis and dorsal to the lateral reticular
      nucleus. Of these cells, double-labelled neurons were found in the commissural
      and medial subdivisions of the caudal nucleus of the tractus solitarius and in
      the rostral ventrolateral medulla including the ventral surface and the nucleus
      paragigantocellularis. The results suggest that neuropeptide Y, angiotensin II
      and galanin may serve as neurochemical messengers in pathways from the medulla to
      the parabrachial complex. The location of double-labelled neurons suggests that
      the information relayed by these neurons is related to autonomic activity.

PMID- 1374538
TI  - Afferent fibres from the guinea-pig ureter: size and peptide content of the
      dorsal root ganglion cells of origin.
AB  - A study was undertaken to determine the segmental organization of the dorsal root
      ganglion cells which give rise to ureteric primary afferent fibres in the guinea
      pig. The size-distribution and peptide content of these dorsal root ganglion
      cells were examined and compared with a sample of all dorsal root ganglion cells
      from the same ganglia. Afferent fibres to the guinea-pig ureter were found to
      arise mainly from dorsal root ganglia L2-L3 and S1-S2. A large contralateral
      component of the afferent innervation of the ureter was found when either the
      right or the left ureter was injected with tracer. This amounted to approximately
      40% of the total labelled cells. The cross-sectional areas of the dorsal root
      ganglion cells of ureteric afferents were found to be at the smaller end of the
      size-range for the whole ganglion. Most (90%) of the cells innervating the ureter
      were immunoreactive for one of the peptides studies, substance P or calcitonin
      gene-related peptide, and a large proportion (65%) were immunoreactive for both.
      This was very different for the ganglia as a whole, where only about 50% of the
      cells were immunoreactive for either of the peptides and only 14% were
      immunoreactive for both peptides. These results show a bilateral afferent
      innervation of the ureter by nerve fibres which, in the vast majority, contain
      substance P and/or calcitonin gene-related peptide.

PMID- 1374539
TI  - Glial cells from adult rat olfactory bulb: immunocytochemical properties of pure
      cultures of ensheathing cells.
AB  - Three morphologically and immunohistochemically distinct types of cell were
      present in primary cultures of adult rat olfactory nerve and glomerular layers of
      the olfactory bulb. One cell type was multipolar and stained positively for glial
      fibrillary acidic protein; a second type had fried egg-like morphology and
      stained with antibodies to epitope ED1; the third cell type had fusiform
      morphology, reacted with antibodies to vimentin and laminin and was glial
      fibrillary acidic protein- and ED1-negative. Trypsinization of these primary
      cultures (3 min, 37 degrees C), detached multipolar and fusiform cells only. When
      detached cells were set up in secondary culture on a glass substrate, fusiform
      cells did not attach, resulting in a pure culture of multipolar cells. Multipolar
      cells were glial fibrillary acidic protein- and myelin basic protein-positive and
      had the properties of so-called ensheathing cells or Blanes' glia.
      Immunoreactivity with anti-nerve growth factor receptor and anti-fibronectin
      allowed us to identify four distinct populations of multipolar ensheathing cells.
      One population was nerve growth factor receptor-positive, fibronectin-negative. A
      second was nerve growth factor receptor-negative and fibronectin-positive. A
      third was positive for both markers and the remaining cells did not stain for
      either of them. The morphological and immunological characteristics of cultured
      cells from olfactory nerve and glomerular layers were similar to those of Schwann
      cells and the similarities could account for the permissivity to axonal growth of
      the olfactory bulb.

PMID- 1374540
TI  - Time-dependent neuroplasticity in mesostriatal projections after unilateral
      removal of vibrissae in the adult rat: compartment-specific effects on
      horseradish peroxidase transport and cell size.
AB  - In adult rats the mystacial vibrissae were clipped on one side of the snout, and
      the influence of this sensory deprivation on crossed and uncrossed striatal
      afferents from the substantia nigra, ventral tegmental area, and retrorubral area
      was examined with the horseradish peroxidase tract tracing technique. Unilateral
      removal of vibrissae was found to affect crossed and uncrossed nigrostriatal
      projections in a time-dependent manner. One to three days after hemivibrissotomy
      an apparent neuronal asymmetry was found in the crossed nigrostriatal projection
      arising in the rostral part of the substantia nigra, with more labeled neurons in
      the projection to the caudate-putamen on the side of vibrissae removal. This
      asymmetry resulted mainly from an asymmetry in the subset of nigrostriatal
      neurons reported to project to the striatal matrix ("dorsal cell type"). In
      contrast, 4-20 days after hemivibrissotomy reversed asymmetries were found in
      crossed and uncrossed nigrostriatal projections, with more labeled neurons in the
      projections to the caudate-putamen of the hemisphere opposite to vibrissae
      removal (the sensory deprived hemisphere). The asymmetry in the uncrossed
      projection was found throughout the substantia nigra, but was also most
      substantial in the projection from its rostral part. The asymmetry in the crossed
      projection was again restricted to the rostral substantia nigra; interestingly,
      however, it was limited to the subset of neurons reported to terminate in the
      striosomes ("ventral cell type"). Evidence was also found for time-dependent
      changes in size of neurons of the crossed nigrostriatal projections, as well as
      for changes in striatal afferents from the ventral tegmental area. The time
      course of these apparent changes in strength of mesostriatal projections is
      similar to the known time course of recovery from behavioral asymmetries induced
      by hemivibrissotomy, which is suggestive of a functional relationship between
      neuronal and behavioral changes. Moreover, the finding of a differential
      influence of hemivibrissotomy on nigrostriatal afferents to striosomes and matrix
      is indicative of a functional dissociation of these two systems.

PMID- 1374541
TI  - Alzheimer's disease: is the decrease of the cholinergic innervation of the
      hippocampus related to intrinsic hippocampal pathology?
AB  - Consistent findings in the hippocampi of patients with Alzheimer's disease are
      the presence of neurofibrillary tangles in pyramidal neurons and the loss of
      choline acetyltransferase activity due to degeneration of hippocampal cholinergic
      terminals. The present study sought to clarify, in the brains of five patients
      with Alzheimer's disease and four controls, whether the loss of cholinergic
      terminals in the hippocampal stratum pyramidale in Alzheimer's disease is related
      to degenerative changes in hippocampal pyramidal cells. A polyclonal antibody to
      human choline acetyltransferase was employed to visualize immunohistochemically
      cholinergic terminals. Hippocampal neurons were stained with Cresyl Violet,
      neurofibrillary tangles with thioflavin S and a monoclonal antibody against
      phosphorylated neurofilament (RT97). Quantification of the stained structures was
      performed in CA4, CA1 and the subiculum, on five sections selected from the
      entire anteroposterior extent of each hippocampus. In the group of Alzheimer
      patients, the densities of cholinergic terminals were homogeneously diminished in
      the three hippocampal subregions in comparison with the controls (32-33%). In
      contrast, a significant loss of pyramidal neurons was found only in CA1, and the
      density of neurofibrillary tangles was markedly increased only in CA1 and the
      subiculum in Alzheimer's disease. These findings suggest that there is no
      relationship between the loss of cholinergic terminals and the degeneration of
      pyramidal cells in the hippocampus of patients with Alzheimer's disease.

PMID- 1374542
TI  - Laterality in the vestibulo-cerebellar mossy fiber projection to flocculus and
      caudal vermis in the rabbit: a retrograde fluorescent double-labeling study.
AB  - The vestibular nuclear input into the flocculus and the uvula and nodulus of the
      caudal vermis was studied in rabbits by means of retrograde transport of the
      fluorescent tracers Fast Blue and Diamidino Yellow. Through simultaneous
      injection of the tracers in the homonymous lobules at either side of the midline,
      the distribution, the preference in laterality and the degree of
      collateralization of vestibulo-cerebellar neurons could be studied. The nucleus
      prepositus hypoglossi was included in the analysis. In the nucleus prepositus
      hypoglossi and in the medial vestibular nucleus 6% of the number of labeled
      neurons contained both tracers, against 4% in the descending vestibular nucleus.
      In the superior vestibular nucleus a statistically significant difference in the
      proportion of double-labeled neurons was found between cases with injections in
      the flocculus (1%) and the caudal vermis (9%). The relative distribution of
      single-labeled neurons projecting to either the flocculus or the caudal vermis
      was similar in most of the vestibular nuclei. A statistically significant
      preference for a projection to the flocculus in favor of one to the caudal
      vermis, was found for neurons in the medial vestibular nucleus and the prepositus
      hypoglossal nucleus. Statistically significant laterality preferences were found
      in the superior vestibular nucleus for the contralateral flocculus.

PMID- 1374543
TI  - Influence of extracellular and intracellular pH on GABA-gated chloride
      conductance in crayfish muscle fibres.
AB  - The effect of intracellular and extracellular pH on GABA-gated Cl- conductance
      was studied using H(+)-selective microelectrodes and a three-microelectrode
      voltage clamp in crayfish leg opener muscle fibres in bicarbonate-free solutions.
      Experimental variation of intracellular pH in the range 6.4-8.0 did not affect
      the GABA-gated conductance. In contrast to this, the GABA-gated conductance was
      sensitive to changes in external pH. Raising the external pH from 7.4 to 8.4
      decreased the GABA-gated peak conductance observed immediately following
      application of GABA by 30%, and a change from 7.4 to 6.4 produced an increase of
      26%. The effect of extracellular pH on the GABA-gated peak conductance was
      approximately linear in the pH range 6.4-8.9. A slight decrease in the slope of
      the pH-conductance relationship was evident in the pH range 5.4-6.4. The
      desensitization of the GABA-gated conductance was also affected by external pH.
      At pH 6.9 the conductance produced by 1 mM GABA showed a desensitization of about
      15%, and at pH 8.9 this value was 34%. Raising the external pH in the presence of
      GABA decreased the GABA-gated peak conductance and increased the fractional
      desensitization, while lowering the external pH produced opposite effects, and
      was capable of repriming the conductance from a desensitized state to the non
      desensitized state. The above results show that the GABA-gated conductance is
      sensitive to changes in external pH in the physiological range, and suggest that
      pH-dependent changes in the postsynaptic efficacy of GABA-mediated inhibition may
      contribute to H+ modulation of neuronal excitability.

PMID- 1374544
TI  - Serotonin-induced stimulation of cortisol secretion from human adrenocortical
      tissue is mediated through activation of a serotonin4 receptor subtype.
AB  - The occurrence of serotonin in the human adrenal gland was demonstrated both by
      immuno-histochemical and biochemical approaches. Using specific polyclonal
      antibodies to serotonin, the presence of numerous immunoreactive cells was
      revealed by means of the peroxidase-antiperoxidase technique. These cells
      exhibited the morphological characteristics of mast cells. Combination of high
      performance liquid chromatography and electrochemical detection showed the
      presence of substantial amounts of both serotonin and its metabolite 5
      hydroxyindolacetic acid in adrenocortical extracts. The role of serotonin in the
      regulation of steroidogenesis from human adrenocortical slices was studied in
      vitro using a perifusion system technique coupled to a specific radioimmunoassay
      for cortisol. Graded doses of serotonin (from 10(-8) M to 3 x 10(-7) M) increased
      cortisol production in a dose-dependent manner. Prolonged exposure of adrenal
      fragments to serotonin (10(-7) M) induced a biphasic response, i.e. a rapid and
      transient increase in cortisol secretion followed by a plateau phase, suggesting
      the existence of a desensitization phenomenon. The stimulatory effect of
      serotonin (10(-7) M) was not altered during infusion of the serotonin1 and/or
      serotonin2 receptor antagonists methysergide (10(-6) M) and ketanserin (10(-6)
      M), respectively. In contrast, ICS 205 930 (10(-6) M), a non-selective
      serotonin3/serotonin4 antagonist, totally abolished the response of adrenal
      slices to serotonin (10(-7) M). The benzamide derivative zacopride, considered as
      a serotonin4 agonist, induced a robust stimulation of cortisol secretion. In
      addition, the corticotropic effects of serotonin (10(-7) M) and zacopride (10(-6)
      M) were not additive. Incubation of adrenocortical fragments with zacopride (10(
      6) M) or serotonin (10(-6) M) caused a significant increase in cAMP formation.
      Taken together, these data suggest that serotonin, locally released by intra
      adrenal mast-like cells, may act as a paracrine factor to stimulate cortisol
      secretion in man. Our results also indicate that serotonin-induced corticosteroid
      production is mediated through activation of a serotonin4 receptor subtype
      positively coupled to adenylate cyclase.

PMID- 1374545
TI  - Striosomal organization of substance P-like immunoreactivity in parkinsonian
      patients.
AB  - We designed this study to evaluate the expression of substance P (SP) in the
      striatum and the globus pallidus in normal controls, idiopathic Parkinson's
      disease (PD), and striatonigral degeneration (SND). We determined
      immunohistochemically the expression of SP in formalin-fixed, paraffin-embedded
      brain tissues using the free-floating method. In normal controls, we observed SP
      like immunoreactivity in the internal segment of the globus pallidus, where the
      SP-positive fibers showed typical "woolly fiber" patterns. SP expression in the
      striatum had the characteristic patchwork of striosomes. Patients with PD showed
      the normal distribution pattern of SP. By comparison, in patients with SND, there
      was a striking diminution of SP in the putamen, while the SP-positive patches
      persisted in the caudate nucleus. This study represents the first unequivocal
      immunohistochemical demonstration of SP-positive striosomes in the human
      striatum.

PMID- 1374546
TI  - Effect of clinical status and treatment on the frequency of CD5+ B cells in
      patients with myasthenia gravis.
AB  - CD5+ B cells comprise a subset of B lymphocytes that may play a pathogenetic role
      in the development of human autoimmune disease. We previously reported a high
      frequency phenotype (greater than 30% CD5+ B cells) in the peripheral blood of
      57% of myasthenia gravis (MG) patients and 13% of controls. We have now examined
      additional patients (n = 41) and controls (n = 27) and continue to find that 44%
      of MG patients have a high-frequency phenotype of CD5+ B cells compared with 7%
      of controls. Serial studies showed that the frequency of CD5+ B cells in
      peripheral blood remained fairly stable for controls and that it may decrease
      with immunosuppressive therapy of MG patients. In patients receiving
      anticholinesterase only or no therapy (n = 21), the age at onset of MG, presence
      or absence of detectable serum anti-acetylcholine receptor antibody, clinical
      extent of MG, and the duration of disease may affect the frequency of CD5+ B
      cells in the blood.

PMID- 1374547
TI  - Levels of CD5+ B lymphocytes do not differ between patients with myasthenia
      gravis and healthy individuals.
AB  - CD5+ B cells might be involved in autoimmunity mainly as autoantibody-producing
      cells. To investigate the possible role of these cells in myasthenia gravis, we
      studied the numbers of CD5+ B cells, CD5- B cells, and CD19+ B cells as well as
      CD5+ T cells in the peripheral blood from 31 patients with myasthenia gravis and
      31 healthy individuals. Both absolute percentages (percent of peripheral blood
      mononuclear cells) and relative percentages (percent of total CD19+ B cells) of
      CD5+ B cells were the same in patients as in controls. The numbers of CD5- B
      cells and CD19+ B cells were the same in both groups, whereas CD5+ T cells were
      lower in the patients. There was no correlation between clinical stage, sex,
      thymectomy, or pathology of thymus and the levels of CD5+ B cells, CD5- B cells,
      or CD19+ B cells. Patients treated with azathioprine had lower levels of CD5+ B
      cells than untreated patients and controls. Our results show that patients with
      myasthenia gravis have the same levels of CD5+ B cells as healthy individuals.

PMID- 1374549
TI  - [Acquired epileptic aphasia--Landau-Kleffner syndrome].
AB  - Authors report about a girl with Landau-Kleffner syndrome. After the history of
      normal developmental milestones at the age of five-and-half year the patient had
      absence seizures, and marked receptiv and expressiv aphasia developed gradually.
      She was found to have Landau-Kleffner syndrome. This entity initially can be
      regarded as deafness or psychiatric reaction. The seizure activity usually has a
      favorable outcome, the aphasia can fluctuate for years. The improvement is more
      likely in promptly treated cases.

PMID- 1374548
TI  - CD4+ T-epitope repertoire on the human acetylcholine receptor alpha subunit in
      severe myasthenia gravis: a study with synthetic peptides.
AB  - The alpha subunit of the nicotinic acetylcholine receptor (AChR) seems crucial in
      the pathogenesis of the autoimmune paralysis myasthenia gravis (MG) because it
      contains both the epitopes that dominate the antibody response against the AChR
      and those recognized by CD4+ AChR-specific T helper (Th) cells. To define the
      repertoire of anti-AChR Th cells, we investigated the response of unselected
      blood CD4+ cells or total lymphocytes, or both, from 22 MG patients to 20-residue
      overlapping synthetic peptides, screening the complete sequence of human-muscle
      AChR alpha subunit. Several epitopes were identified. Only the most severely
      affected patients recognized alpha subunit epitopes, and they were mainly young
      women. Detection of in vitro AChR-specific CD4+ response was facilitated by
      removal of the CD8+ cells because in two patients a clear response to several
      alpha subunit peptide sequences could be detected when CD(8+)-depleted cells were
      used, while their total peripheral blood mononuclear cell population did not
      respond to any alpha subunit peptide. Although each patient had a unique pattern
      of peptide recognition, four immunodominant regions recognized by long-term AChR
      specific CD4+ T-cell lines, or flanking peptide sequences, were recognized most
      frequently (residues 48-67, 101-137, 293-337, and 308-437).

PMID- 1374550
TI  - Immunohistochemical analysis of synovial membranes from inflammatory and non
      inflammatory arthritides: scarcity of CD5 positive B cells and IL2 receptor
      bearing T cells.
AB  - Rheumatoid Arthritis (RA) synovial membranes were examined by single and dual
      immunohistological techniques with a number of monoclonal antibodies against
      lymphocyte and macrophage related antigens. CD4 positive T lymphocytes frequently
      expressed MHC Class II antigens and were found in sublining collections in close
      association with activated macrophages as well as B lymphocytes. CD8 positive T
      cells surrounded these collections as well as being scattered throughout the
      membrane and also frequently expressed MHC Class II antigens. IL2 receptor (IL2r)
      expression on T cells and CD5 expression on B cells were rarely seen in these
      synovial membranes. Similar immunohistological architecture was found in synovial
      membranes from patients with psoriatic arthritis (PA) and Reiter's Syndrome (RS).
      Normal synovium contained few T cells, with few cells expressing MHC Class II
      antigens. Synovium from osteoarthritis (OA) patients also demonstrated similar
      immunohistological changes to those found in inflammatory arthritides, suggesting
      that there are only quantitative rather than qualitative differences between the
      synovial membrane immunohistological architecture from patients with inflammatory
      and noninflammatory arthritides.

PMID- 1374551
TI  - Clear cell sarcoma of kidney: report of the first Malaysian case.
AB  - Clear cell sarcoma of kidney (CCSK) is a rare but distinct tumor of childhood
      frequently confused with Wilms' tumor (nephroblastoma). It has a characteristic
      histology, a marked predilection for metastasis to bone, and an aggressive
      clinical course with a high relapse rate in spite of surgical excision,
      chemotherapy and radiotherapy. We report the first histologically proven CCSK in
      a Malaysian patient. This was an 8-mth-old Malay boy who was clinically diagnosed
      to have stage I Wilms' tumor. Despite treatment, he developed multiple metastases
      10 mths after initial presentation and died soon after. Emphasis is placed on
      recognizing this entity in view of (1) its naturally aggressive behaviour and (2)
      the prospect of improving prognosis with currently recommended intensified
      chemotherapeutic regimes. Its immunohistochemical profile of vimentin-positivity
      and negativity for epithelial membrane antigen, cytokeratin and Factor-8 related
      antigen is more in favour of a mesenchymal or glomerular origin than a tubular or
      vascular origin.

PMID- 1374552
TI  - Velo-cardio-facial syndrome associated with ventricular septal defect, pulmonary
      atresia, and hypoplastic pulmonary arteries.
AB  - We report on 15 patients with velo-cardiofacial syndrome who had a severe form of
      tetralogy of Fallot (pulmonary atresia, ventricular septal defect, and
      hypoplastic pulmonary arteries). Noncardiac anomalies in these patients included
      typical facial and ear anomalies in 15, nasal speech in 13, palate anomalies in
      10, and developmental delay in 10. Seven patients had significant bronchospasm,
      which has not been reported in association with the velo-cardio-facial syndrome.
      All 15 patients had severe abnormalities of the arborization of the pulmonary
      arterial tree, which also has not been reported in velo-cardio-facial syndrome.
      All patients underwent staging operations to prepare the true pulmonary vascular
      tree for complete repair of the defect (five underwent complete repair and three
      survived). Of the remaining 10 patients, 6 are awaiting further operation, 3 are
      not candidates for complete repair, and 1 has died.

PMID- 1374554
TI  - Reverse transcriptase inhibits Taq polymerase activity.
AB  - Detection of viral RNA by polymerase chain reaction (PCR) requires the prior
      reverse transcription of the viral RNA. In order to minimise the number of manual
      manipulations required for processing large numbers of samples, we attempted to
      design a system whereby all the reagents required for both reverse transcription
      and amplification can be added to one tube and a single, non-interrupted thermal
      cycling program performed. Whilst attempting to set up such a one-tube system
      with Taq polymerase (Taq; Biotech International) and avian myoblastosis virus
      (AMV) reverse transcriptase (RT), we noticed a substantial decrease in the
      sensitivity of detection of viral RNA. Investigation of this phenomenon has
      revealed direct interference of RT with Taq polymerase. Evidence supporting this
      conclusion includes the following observations: (1) increasing the ratio of Taq
      to RT improves sensitivity; (2) adding non-homologous RNA improves sensitivity;
      (3) RT that has been heat inactivated prior to Taq addition does not exert this
      effect; (4) the effect is not sequence restricted; (5) the Mg2+ ions are not
      sequestered by RT. In addition, the effect is not limited to AMV RT, Moloney
      murine leukaemia virus RT also affects Taq activity.

PMID- 1374553
TI  - Ribonuclease P RNA and protein subunits from bacteria.

PMID- 1374555
TI  - Mutations in E.coli 16s rRNA that enhance and decrease the activity of a
      suppressor tRNA.
AB  - The in vivo expression of mutations constructed within helix 34 of 16S rRNA has
      been examined together with a nonsense tRNA suppressor for their action at stop
      codons. The data revealed two novel results: in contrast to previous findings,
      some of the rRNA mutations affected suppression at UAA and UAG nonsense codons.
      Secondly, both an increase and a decrease in the efficiency of the suppressor
      tRNA were induced by the mutations. This is the first report that rRNA mutations
      decreased the efficiency of a suppressor tRNA. The data are interpreted as there
      being competition between the two release factors (RF-1 and RF-2) for an
      overlapping domain and that helix 34 influences this interaction.

PMID- 1374556
TI  - The topography of the 3'-terminal region of Escherichia coli 16S ribosomal RNA;
      an intra-RNA cross-linking study.
AB  - 30S ribosomal subunits, 70S ribosomes or polysomes from E. coli were subjected to
      mild ultraviolet irradiation, and the 3'-terminal region of the 16S RNA was
      excised by 'addressed cleavage' using ribonuclease H in the presence of suitable
      complementary oligodeoxynucleotides. RNA fragments from this region containing
      intra-RNA cross-links were separated by two-dimensional gel electrophoresis and
      the cross-link sites identified by our standard procedures. Five new cross-links
      were found in the 30S subunit, which were localized at positions 1393-1401 linked
      to 1531-1532, 1393-1401 linked to 1506, 1393-1401 to 1502-1504, 1402-1403 to 1498
      1501, and 1432 to 1465-69, respectively. In 70S ribosomes or polysomes the first
      four of these were absent, but instead two cross-links between the 1400-region
      and tRNA were observed. These results are discussed in the context of the
      tertiary folding of the 3'-terminal region of the 16S RNA and its known
      functional significance as part of the ribosomal decoding centre.

PMID- 1374557
TI  - Molecular design of a eukaryotic messenger RNA and its chemical synthesis.
AB  - A designed mRNA consisting of 42 ribonucleotides having the cap structure was
      synthesized. The capped leader sequence of the brome mosaic virus (BMV) mRNA 4,
      m7G5'pppGUAUUAAUA (F-1), was synthesized by the phosphotriester method and
      followed by the capping reaction. A 32-mer consisting of an initiation codon
      (AUG), the coding region corresponding to a bacterial pheromone cAD1 and two stop
      codons, was constructed by the 18-mer (F-2) and 14-mer (F-3), which were
      synthesized by the phosphoramidite method. 2'-,3'-O-Methoxymethylene-guanosine 5'
      phosphate was condensed with F-3 using P1-2',3'-O-methoxymethyleneguanosine-5'-yl
      P2-adenosine-5'-yl pyrophosphate (9) with T4 RNA ligase. The chemically
      synthesized RNA fragments were ligated successively with T4 RNa ligase to afford
      the whole RNA molecule.

PMID- 1374558
TI  - Transformation of a novel direct-repeat repressor element into a promoter and
      enhancer by multimerisation.
AB  - Studies on the regulation of interferon (IFN) responsive genes have mainly been
      centred on the highly conserved IFN stimulated responsive elements (ISREs) which
      can mediate type I and II IFN inducibility. To date little is known about other
      functional cis-acting regulatory motifs in IFN responsive genes. We report here
      on the identification of a repressor element in the human MxA gene defined to a
      19 base pair (bp) region which houses a 9 bp direct repeat. DNA-specific protein
      binding on this element is not affected by IFN treatment and is distinct from
      ISRE binding proteins. Remarkably, contrary to expectations, when the repressor
      element is multimerised and spliced, in either orientation, to a reporter gene it
      behaves like a functional, constitutive promoter. Positioning the multimerised
      element in front of the SV40 enhancerless promoter also led to enhanced
      expression. The same protein(s) seem to bind to both the single repressor element
      and its multimerised form. This discovery of phenotypic reversal on a repressor
      element via multimerisation may have important implications in vivo.

PMID- 1374559
TI  - The nature of preferred hairpin structures in 16S-like rRNA variable regions.
AB  - Variable length hairpins in 16S-like rRNA show a predominance for tetra-loops,
      its degree correlates with the protein content of the ribosome. The number of
      base-pairs adjacent to the loop (the tip size) and the nearest neighbor
      composition contribute to the stability of hairpin structures. The average tip
      size in length variable hairpins correlates with the thermophilicity of the
      organism, i.e. in temperate environments less stable stem structures are
      tolerated or even necessary. The most abundant loop families UUCG, GCAA, and CUUG
      occur most frequently at loop sizes 3, 2, and 7, respectively. Short tips of size
      less than or equal to 4 generally prefer nearest-neighbor combinations that
      result in CCC-GGG. Loop-specific tipmost nearest neighbors are revealed at longer
      tips: CUC(UUCG)GAG, GUA(GCAA)UAC with a maximum at tip sizes 5-6, and
      GWG(CUUG)CWC. Conserved hairpins, however, prefer variants of the UUCG and GCAA
      motifs with additional purines. Minor loop families and single motifs such as
      UUUA, UUUU, CUUGU, UUCGG, and UUU are investigated for preferable tip sizes and
      nearest-neighbor composition. Specific features are revealed for prominent hexa
      loops.

PMID- 1374560
TI  - Construction of a chromosome-enriched HpaII library from flow-sorted wheat
      chromosomes.
AB  - We report here the first successful generation of a chromosome-enriched library
      from flow sorted plant chromosomes. Chromosomes with a characteristic DNA content
      (a peak) were sorted from a synchronized cell culture (TaKB1, derived from
      Triticum aestivum). A HpaII library was constructed from the sorted chromosomes
      and half of the cloned DNA sequences analysed are unique or low copy.
      Approximately half of these sequences when used as probes detect sequences on
      wheat chromosome 4A. The generation and analysis of the chromosome library is
      described in detail and the prospects of using flow-sorted plant chromosomes
      discussed.

PMID- 1374561
TI  - [Calcofluor-white staining in the identification of Pneumocystis carinii].
AB  - Calcofluor white stain is widely used as a fluorescent stain in mycology.
      Recently, it was found that by calcofluor white staining Pneumocystis carinii
      cysts exert a highly characteristic staining pattern. We retested fifteen
      clinical specimens which were known to be positive for Pneumocystis carinii
      (diagnosis made by a methenamine silver stain). Calcofluor white stain proved to
      be a simple, rapid, and inexpensive method for detecting Pneumocystis carinii in
      clinical specimens.

PMID- 1374562
TI  - Recurrent alpha beta loop structures in TIM barrel motifs show a distinct pattern
      of conserved structural features.
AB  - A systematic survey of seven parallel alpha/beta barrel protein domains, based on
      exhaustive structural comparisons, reveals that a sizable proportion of the alpha
      beta loops in these proteins--20 out of a total of 49--belong to either one of
      two loop types previously described by Thornton and co-workers. Six loops are of
      the alpha beta 1 type, with one residue between the alpha-helix and beta-strand,
      and 13 are of the alpha beta 3 type, with three residues between the helix and
      the strand. Protein fragments embedding the identified loops, and termed alpha
      beta connections since they contain parts of the flanking helix and strand, have
      been analyzed in detail revealing that each type of connection has a distinct set
      of conserved structural features. The orientation of the beta-strand relative to
      the helix and loop portions is different owing to a very localized difference in
      backbone conformation. In alpha beta 1 connections, the chain enters the beta
      strand via a residue adopting an extended conformation, while in alpha beta 3 it
      does so via a residue in a near alpha-helical conformation. Other conserved
      structural features include distinct patterns of side chain orientation relative
      to the beta-sheet surface and of main chain H-bonds in the loop and the beta
      strand moieties. Significant differences also occur in packing interactions of
      conserved hydrophobic residues situated in the last turn of the helix. Yet the
      alpha-helix surface of both types of connections adopts similar orientations
      relative to the barrel sheet surface. Our results suggest furthermore that
      conserved hydrophobic residues along the sequence of the connections, may be
      correlated more with specific patterns of interactions made with neighboring
      helices and sheet strands than with helix/strand packing within the connection
      itself. A number of intriguing observations are also made on the distribution of
      the identified alpha beta 1 and alpha beta 3 loops within the alpha/beta-barrel
      motifs. They often occur adjacent to each other; alpha beta 3 loops invariably
      involve even numbered beta-strands, while alpha beta 1 loops involve
      preferentially odd beta-strands; all the analyzed proteins contain at least one
      alpha beta 3 loop in the first half of the eightfold alpha/beta barrel. Possible
      origins of all these observations, and their relevance to the stability and
      folding of parallel alpha/beta barrel motifs are discussed.

PMID- 1374563
TI  - Regulation of fracture repair by growth factors.
AB  - Fractured bones heal by a cascade of cellular events in which mesenchymal cells
      respond to unknown regulators by proliferating, differentiating, and synthesizing
      extracellular matrix. Current concepts suggest that growth factors may regulate
      different steps in this cascade (10). Recent studies suggest regulatory roles for
      PDGF, aFGF, bFGF, and TGF-beta in the initiation and the development of the
      fracture callus. Fracture healing begins immediately following injury, when
      growth factors, including TGF-beta 1 and PDGF, are released into the fracture
      hematoma by platelets and inflammatory cells. TGF-beta 1 and FGF are synthesized
      by osteoblasts and chondrocytes throughout the healing process. TGF-beta 1 and
      PDGF appear to have an influence on the initiation of fracture repair and the
      formation of cartilage and intramembranous bone in the initiation of callus
      formation. Acidic FGF is synthesized by chondrocytes, chondrocyte precursors, and
      macrophages. It appears to stimulate the proliferation of immature chondrocytes
      or precursors, and indirectly regulates chondrocyte maturation and the expression
      of the cartilage matrix. Presumably, growth factors in the callus at later times
      regulate additional steps in repair of the bone after fracture. These studies
      suggest that growth factors are central regulators of cellular proliferation,
      differentiation, and extracellular matrix synthesis during fracture repair.
      Abnormal growth factor expression has been implicated as causing impaired or
      abnormal healing in other tissues, suggesting that altered growth factor
      expression also may be responsible for abnormal or delayed fracture repair. As a
      complete understanding of fracture-healing regulation evolves, we expect new
      insights into the etiology of abnormal or delayed fracture healing, and possibly
      new therapies for these difficult clinical problems.

PMID- 1374564
TI  - Tumor necrosis factor, interleukin, and interferon induced changes in lipid
      metabolism as part of host defense.
AB  - As the immune response is activated during infection, multiple changes in lipid
      metabolism, especially increased production of VLDL, occur. Many of the cytokines
      that mediate the immune response are able to produce such changes in lipid
      metabolism in vivo. The induction of hypertriglyceridemia or other changes in
      lipid metabolism during infection do not directly cause the wasting syndrome. It
      appears that such changes in lipid metabolism may be beneficial to the host, as
      lipoproteins inactivate a variety of infectious agents. Cytokine-driven hepatic
      VLDL production during infection most likely represents a part of the acute phase
      response. The body is thus able to increase serum lipids during infection, or at
      least maintain triglyceride-rich lipoproteins despite the anorexia of infection.
      In this manner, the anti-infective, protective effects of lipoproteins are
      maintained.

PMID- 1374566
TI  - Parasympathetic NANC-secretion of saliva in the mink, and effects of substance P
      and VIP.
AB  - In both parotid and submandibular glands a parasympathetic non-adrenergic, non
      cholinergic (NANC) nerve-evoked secretion of saliva was demonstrated. Saliva
      evoked by exogenous substance P was poor in protein, while saliva evoked by VIP
      was protein-rich. In a subthreshold dose for fluid secretion VIP released protein
      and potentiated the responses elicited by substance P, particularly regarding the
      output of protein. The two neuropeptides may contribute to the parasympathetic
      NANC secretion of saliva in the mink. Further, agonists responsible for the
      secretory NANC response are also likely to contribute to the secretory response
      of the glands to parasympathetic stimulation in the absence of autonomic receptor
      blockade in this species.

PMID- 1374565
TI  - Reduced gastric acid inhibitory effect of a pGIP(1-30)NH2 fragment with potent
      pancreatic amylase inhibitory activity.
AB  - Gastric inhibitory polypeptide (GIP) strongly stimulates insulin secretion in the
      presence of glucose and also stimulates somatostatin release from gastric mucosa.
      It was reported recently that both stimulatory activities can be dissociated by
      removing the C-terminal 12 amino acid residues. Since insulin and somatostatin
      are involved in regulation of exocrine pancreatic and gastric secretion in rats,
      we compared the inhibitory effects of pGIP and the pGIP(1-30)NH2 fragment on
      pancreatic amylase and gastric acid secretion. pGIP(1-30)NH2 displayed full
      activity on inhibition of bombesin (BN)-stimulated amylase release relative to
      GIP itself, but was about 10-fold less potent in inhibiting gastric acid
      secretion. These results suggest that the receptors involved in these two events
      have quite different ligand binding requirements and that more specific analogues
      of GIP can be designed which should be of value in elucidating the physiological
      roles of this hormone.

PMID- 1374567
TI  - [The immunological characterization of 63 cases of Hodgkin's disease with a panel
      of 8 antibodies].
AB  - Sixty three cases of Hodgkin's disease are studied (two with lymphonodular
      predominance, 15 with diffuse lymphocyte predominance, 26 nodular sclerosis, 15
      mixed cell and 5 lymphocyte depletion) with a panel of 8 monoclonal antibodies,
      material routinely used and included in paraffin: Ber H2 (CD30), Leu M1 (CD15),
      Common Leukocyte Antigen (CD45), L26 (CD20), MB2, UCHL1 (CD45 RO), MTI (CD43) and
      Epithelial Membrane Antigen. Ber H2 turned out to be the most usefull marker,
      positive in 100% of cases, independently of the histologic type. Positiveness
      with Leu M1 ranged from 100% (2/2 cases) of lymphonodular predominance, to 53.3%
      (8/15 cases) of diffuse lymphocyte predominance. The reactivity of the rest was
      variable, 1 though it is note worthy the positiveness of B markers (L26, MB2) in
      the two cases with lymphonodular predominance. In the other subtypes, reactivity
      with L26 was greater than that with MB2. T cell marker expression was minimal,
      except for the positiveness in 40% of cases (2/5) of the lymphocyte depletion
      type. In addition, the results of other series are revised and as a result the
      possible histogenesis of Hodgkin's disease is discussed.

PMID- 1374568
TI  - [Current tuberculosis mortality world-wide].
AB  - The mortality rate still is an important index for assessment of tuberculosis.
      Statistical records are kept on the mortality rate on a worldwide basis--more
      than in the case of other tuberculosis parameters. They allow us to make valuable
      comparisons. They are also useful because the mortality is closely related to the
      morbidity. The present thesis is based on comparative figures from the 1989
      volume of the WHO Health Statistics Annual. Various countries have been specially
      selected by the publisher--and subsequently also by us--for sake of clarity. The
      figures vary strongly within these countries, which was to be expected. The
      mortality rate varies in Europe (for each 100,000 residents) e.g. from 0.2 in the
      Netherlands to 8.15 in the Soviet Union. In the Americas the rates vary from 0.4
      for Canada to 12.9 for Ecuador. In the Western Pacific region the mortality rates
      vary from 0.35 for Australia to 14.65 for China. On a worldwide basis, the share
      of deaths from tuberculosis among all causes of death varies from 0.02% in the
      Netherlands to 2.10% in the Republic of Korea. The relation of tuberculosis
      deaths with regard to sexes in Switzerland: 75.7% men, 24.3% women, which is more
      or less the European average. The lower the mortality rate for tuberculosis are,
      the lower the difference between the sexes appears to be. Similar facts are found
      with regard to the distribution of tuberculosis deaths according to age groups:
      the lower the tuberculosis rate, the more tuberculosis is found in older age
      groups. The tuberculosis deaths are percentage-wise similarly distributed to the
      respiratory organs and the other tuberculosis forms.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1374569
TI  - The roles of histamine, leukotriene C4 and bradykinin on nasal vascular
      permeability in experimental nasal allergy of guinea pigs.
AB  - The releases of histamine, leukotriene C4 (LTC4) and bradykinin into the nasal
      cavity were measured following nasal antigenic challenge in ovalbumin (OA)
      sensitized guinea pigs, or following nasal stimulation with one of these chemical
      mediators in OA-non-sensitized animals. In sensitized animals, increased vascular
      permeability of nasal mucosa was recognized immediately after antigenic
      stimulation and lasted for 90 minutes. The release of histamine into the nasal
      lavage fluid was observed only immediately after the antigenic stimulation. The
      releases of LTC4 and kinins into the nasal lavage fluid were augmented not only
      immediately after the antigenic challenge, but also 60 to 90 minutes after the
      stimulation. Nasal stimulation with one of these chemical mediators also
      increased nasal vascular permeability, but lasted for less than 40 minutes. These
      results suggest that the antigen-induced release of these chemical mediators
      might play some important roles in early increase of nasal vascular permeability,
      and that the increase of LTC4 and kinin levels might be involved in the prolonged
      nasal vascular permeability after nasal allergic response.

PMID- 1374570
TI  - Multiple ICAM-1 (CD54) epitopes are involved in homotypic B-cell adhesion.
AB  - Two monoclonal antibodies (MoAbs), F10.2 and F10.3, were selected for their
      ability to interfere in homotypic adhesion of human B cells. Precipitation
      studies and binding to intercellular adhesion molecule 1 (ICAM-1, CD54) cDNA
      transfected COS cells revealed that both MoAbs are directed against ICAM-1. The
      binding of MoAb F10.2 was inhibited by LB-2, a MoAb recognizing the NH2-terminal
      immunoglobulin-like domain of ICAM-1. This suggests that the epitope recognized
      by F10.2 is located on the first domain of the ICAM-1 molecule. Binding of the
      other MoAb, F10.3, was not inhibited by F10.2 nor by two other MoAbs mapping to
      the first domain of the ICAM-1 molecule. The ability of F10.3 to bind to ICAM-1
      is influenced by glycosylation, suggesting that this epitope is located on one of
      the domains carrying possible glycosylation sites, i.e. domain 2, 3 or 4. The
      ICAM-1 epitopes recognized by F10.3 and LB-2 or F10.2 co-operated in homotypic
      adhesion of cells from the EBV cell line ML1. These results suggest that in
      addition to an epitope located on domain 1 of the ICAM-1 molecule, another
      epitope whose exposure can be regulated by glycosylation is involved in homotypic
      B-cell adhesion of cell line ML1.

PMID- 1374571
TI  - Expression of CD26 (dipeptidyl peptidase IV) on memory and naive T lymphocytes.
AB  - It has been suggested that human CD26-positive T lymphocytes represent the memory
      pool of the cellular immune system. For proof of this suggestion we analysed the
      responsiveness of CD26-positive and CD26-negative T lymphocytes after antigenic
      stimulation in limiting dilution experiments. After stimulation with tetanus
      toxoid (TT) the number of proliferating cells within the CD26-positive subset was
      two- to sixfold higher than that within the CD26-negative subset. These
      differences in responsiveness were also detectable between CD4+/CD26+ and
      CD4+/CD26- T cells. To further investigate the memory character of the cells,
      human peripheral blood mononuclear cells were stimulated with TT for 7 or 14
      days. Thereafter, CD26+ and CD26- T cells were isolated and restimulated with TT
      in limiting dilution experiments. Responding cells were found not only within the
      CD26-positive subset but also within the CD26-negative subset, and their number
      increased with time. Surface marker analysis of freshly isolated human T
      lymphocytes or T-cell clones indicated that CD26 is not a stable cell surface
      marker. Furthermore, CD26 is both absent and present on CD29-positive or CD45RA
      positive cells, indicating no association of CD26 with surface markers for memory
      or naive T cells, respectively. These results strongly argue against the
      hypothesis that CD26-positive T cells represent the memory pool. We conclude that
      CD26 is an activation marker of T lymphocytes, which is associated with
      reactivity on naive and memory cells.

PMID- 1374572
TI  - Lumbar epidural injection of steroid in acute prolapsed intervertebral discs. A
      prospective study.

PMID- 1374573
TI  - [Has the care of dying patients in hospitals changed? A study of terminal care at
      the Diaconal hospital in 1977 and 1987].
AB  - A research project conducted at the Norwegian Lutheran Hospital in 1977 (213
      deaths) was repeated in 1987 (100 deaths). The purpose was to discover if and how
      terminal care had changed during the ten years. Data sources were case records,
      nurses' reports, interviews with closest relatives about 12 weeks after the death
      (response 95% in 1977 and 72% in 1987). Openness about death had not increased.
      There was some improvement of palliative treatment. In 1987, 79% of all terminal
      patients had received such treatment, compared with 51% in 1977. The percentage
      receiving life prolonging treatment, such as parenteral supply of fluids, had
      fallen from 62% in 1977 to 25% in 1987, and the percentage treated with
      antibiotics from 31% in 1977 to 15% ten years later.

PMID- 1374574
TI  - [Accidents with radioactive pollution. Can we do something?].
AB  - Nuclear accidents are a cause of widespread fear. Treatment of patients exposed
      to high doses of total body irradiation has very often been ineffective. The use
      of hematopoietic growth factors may be a new way of treating these patients. This
      article describes results from studies of total body irradiated animals and
      clinical experience from treating humans who have been involved in nuclear
      accidents. G-CSF or GM-CSF administered within three hours after a nuclear
      accident seems to be of value. Surprisingly, so far bone marrow transplantation
      seems to be of limited value. Intravenous transfusions of thrombocytes and red
      blood cells, and the treatment of burns and gastrointestinal symptoms, are
      important parts of the medical therapy.

PMID- 1374575
TI  - Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted
      magnetic resonance microscopy.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to measure apparent diffusion
      coefficients in rat brain tissue exposed to ouabain, glutamate, and N-methyl-D
      aspartate and to compare them with apparent diffusion coefficients found in acute
      cerebral ischemia. METHODS: The apparent diffusion coefficient was measured using
      magnetic resonance microscopy in four groups of Sprague-Dawley rats after
      occlusion of the right middle cerebral artery and ipsilateral common carotid
      artery (n = 7), after ouabain exposure (n = 6), during glutamate exposure (n =
      7), or during N-methyl-D-aspartate exposure (n = 3). Ouabain, glutamate, and N
      methyl-D-aspartate were applied via an intracerebrally implanted microdialysis
      membrane. RESULTS: Three hours after the induction of focal cerebral ischemia, a
      33% reduction in the apparent diffusion coefficient was observed in the right
      dorsolateral corpus striatum and olfactory cortex. After ouabain exposure,
      reductions in the apparent diffusion coefficient were observed within a 1,500
      microns radius of the microdialysis membrane. Quantitative analysis revealed that
      apparent diffusion coefficient values in ischemic and ouabain-exposed tissue fell
      within the same range. Glutamate and N-methyl-D-aspartate reduced the brain
      tissue apparent diffusion coefficient by 35% and 40%, respectively. CONCLUSIONS:
      On the basis of these findings, we conclude that ischemia-induced apparent
      diffusion coefficient reductions are likely caused by a shift of extracellular to
      intracellular water.

PMID- 1374576
TI  - Serum prostate-specific antigen after post-prostatectomy radiotherapy.
AB  - External beam radiotherapy was administered to 39 patients after radical
      prostatectomy for adenocarcinoma. Thirty-seven of 39 patients had detectable
      levels of serum prostate-specific antigen (PSA) prior to irradiation as evidence
      of residual carcinoma (biochemical evidence of disease). Two patients also had
      palpable recurrences. Pathologic analysis of the surgical specimens suggested
      that positive surgical margins, seminal vesicle or lymph node involvement, or
      high Gleason pattern scores are associated with measurable PSA after surgery.
      Follow-up ranged from two to seventy-four months (mean 26.8 months). To date,
      local control has been achieved in all but 1 patient (including 2 patients with
      palpable tumor prior to radiotherapy). Two distinct risk groups for the
      development of distant metastases based on the trend of the PSA in relation to
      the duration of follow-up after radiotherapy are defined. In the high-risk group
      (those patients with a rising PSA), in 9 of the 18 bone metastases have
      developed, while none of the 17 low-risk patients have metastatic disease.

PMID- 1374577
TI  - Treatment of dogs in hemorrhagic shock by intraosseous infusion of hypertonic
      saline and dextran.
AB  - Under isoflurane anesthesia, 50% of the calculated blood volume was removed from
      11 dogs. After 30 minutes, five dogs were treated with hypertonic saline and
      dextran (HSD) (5 mL/kg) followed by isotonic saline solution (2 mL/kg)
      intraosseously. Six dogs (controls) received isotonic saline (7 mL/kg)
      intraosseously. All treatments were administered through the medullary cavity of
      the tibia over a 30-minute period. Cardiac output, mean arterial pressure,
      central venous pressure, packed cell volume, total protein, and blood gases were
      monitored for 4 hours. Cardiac output, mean arterial pressure, and circulating
      volume (indicated by packed cell volume and total protein) were significantly
      improved after administration of HSD. We conclude that intraosseous infusion of
      HSD is efficacious in treating hemorrhagic shock and believe the technique may
      prove to be useful in clinical situations when intravenous lines cannot be
      established rapidly.

PMID- 1374578
TI  - High-temperature short-time heat inactivation of HIV and other viruses in human
      blood plasma.
AB  - An ultra-short-time heating system was used to process blood plasma spiked with
      various viruses (HIV, vesicular stomatitis virus, encephalomyocarditis virus).
      Virus reduction and recovery of plasma proteins were measured at various
      temperatures from 65 to 85 degrees C. Processing at 77 degrees C and 0.006 s
      resulted in a high level of virus kill, including greater than or equal to 4.4
      log10 HIV, while maintaining protein structure and activity essentially intact.

PMID- 1374579
TI  - Improved serodiagnosis of posttransfusion hepatitis C virus infection by a second
      generation immunoassay based on multiple recombinant antigens.
AB  - Serial serum samples from 35 patients with posttransfusion non-A, non-B hepatitis
      in a prospective study were tested for antibody to hepatitis C virus (HCV) by a
      multiple recombinant antigen based immunoassay [anti-HCV (2nd); Abbott]. Of them,
      23 were positive for anti-C100, and 27 were positive for HCV RNA by polymerase
      chain reaction. By anti-HCV (2nd), 28 patients were positive, and all except 1 of
      the 28 patients were positive for HCV RNA. A total of 24 patients, who became HCV
      RNA positive at the acute stage and who were negative for both anti-C100 and anti
      HCV (2nd) before transfusion, were considered to have posttransfusion hepatitis
      C. The mean time to seroconversion for anti-HCV (2nd) was 7.5 or 12.1 weeks after
      the onset of hepatitis or the date of transfusion, respectively, and was
      generally 6 weeks earlier than that detected by anti-C100. However,
      seroconversion was delayed in 2 hepatitis B surface antigen carriers as compared
      with anti-C100. The anti-C100 assay detected 20 (83%) and the anti-HCV (2nd) all
      24 patients with documented posttransfusion hepatitis C. The second-generation
      test is, therefore, better than conventional anti-C100 for the early diagnosis of
      HCV infection.

PMID- 1374580
TI  - Autoantibodies in HIV-infected hemophilia patients against different epitopes on
      CD4+ lymphocytes and recombinant CD4.
AB  - We studied 684 sera obtained from 20 hemophilia patients with AIDS/AIDS-related
      complex (ARC), 89 asymptomatic HIV+, 76 HIV- hemophilia patients and 151 healthy
      controls for antibodies against recombinant CD4 (rCD4). Twenty-two percent of
      AIDS/ARC patients, 10% of asymptomatic HIV+ patients, 17% of HIV-patients, and 1%
      of healthy controls had anti-rCD4 antibodies. Purified anti-rCD4 antibodies did
      not react with human CD4+ lymphocytes. This may explain why formation of anti
      rCD4 antibodies correlated neither with the occurrence of autoantibodies against
      CD4+ lymphocytes nor with a decrease in CD4+ cell counts. Antibodies that were
      eluted from CD4+ lymphocytes after sequential adsorption and elution with
      separated CD8+ and CD4+ cells reacted with CD4+ lymphocytes of only some healthy
      individuals, suggesting diversity of CD4 expression.

PMID- 1374581
TI  - Substance P- and calcitonin gene-related peptide-like immunoreactive neurons in
      the rat trigeminal ganglion--with special reference to meningeal and pineal
      innervation.
AB  - The distribution of perikarya showing substance P- (SP) or calcitonin gene
      related peptide-like immunoreactivity (CGRP-LI) in the rat trigeminal ganglion
      (TG) were investigated by means of immunohistochemical methods. Approximately 50%
      of the perikarya contain CGRP while SP-LI was observed in 1/3 of the cells. IR
      fibres were seen to leave the ganglion via the ophthalmic, maxillary, and
      mandibular nerves. The combination of peptide histochemistry and retrograde
      labelling of cells in the ganglion following injection of a fluorescent tracer
      into the pineal gland reveals that few SP- or CGRP-LI trigeminal neurons
      innervate the pineal gland. In contrast, the vast majority of perikarya in the TG
      were labelled upon application of the tracer to the meningeal surface supporting
      the view that meninges and meningeal arteries in rodents are heavily innervated
      by SP- and CGRP-LI trigeminal neurons.

PMID- 1374582
TI  - Penetration of lomefloxacin into human prostatic tissue.
AB  - Serum and prostatic tissue concentrations of lomefloxacin were measured in 12
      elderly patients who underwent transurethral resection of the prostate after
      receiving a single oral dose of 400 mg. The peak serum concentration of
      lomefloxacin was 2.5-10.0 micrograms/mL (mean, 5.2 +/- 1.9 micrograms/mL). During
      surgery, serum and tissue concentrations averaged 4.6 +/- 2.2 micrograms/mL and
      6.5 +/- 2.7 micrograms/g, respectively. The ratio of tissue to serum
      concentrations was 1.53 +/- 0.54. The levels of lomefloxacin in serum and
      prostatic tissue were found to be higher than the minimum inhibitory
      concentration (MIC) values for most urinary tract pathogens.

PMID- 1374583
TI  - Case report: alternation therapy with antileukemic agents and recombinant human
      granulocyte colony-stimulating factor for RAEB in transformation.
AB  - Under the assumption that in some patients with refractory anemia with excess of
      blasts (RAEB), the abnormal clones might be less responsive to granulocyte colony
      stimulating factor than normal clones, the authors tried alternation therapy with
      a recombinant form of this factor (rhG-CSF) and antileukemic agents in the
      treatment of two patients with RAEB in transformation. After repetition of the
      short-cycled alternation therapy, the hematologic findings of both patients were
      completely normalized and have remained so without any adverse side effects under
      the continuation of this therapy for more than 5 months. Judging from our
      clinical experience, the alternation therapy may be a new efficient therapeutic
      strategy for RAEB and some types of slowly progressive leukemia.

PMID- 1374584
TI  - Infiltration of helper/inducer T lymphocytes heralds central nervous system
      damage in human T-cell leukemia virus infection.
AB  - Cellular infiltrates in new and old lesions in two cases of human T-cell leukemia
      virus associated myelopathy (HAM) were analyzed with anti-CD3 antibody and OPD4
      antibody recognizing CD4 + CD45RO + T lymphocytes. A subset of CD4 lymphocytes
      with helper/inducer function and labeled with OPD4 constitutes up to 65% of CD3
      cells in new lesions in the pons and the cervical cord. In contrast, nonhelper
      cells and macrophages were dominant in long-standing spinal cord lesions of these
      HAM cases and inflammatory lesions in two cases of Japanese encephalitis. Thus,
      unlike in viral infections, the central nervous system (CNS) tissue damage
      associated with human T-cell leukemia virus (HTLV-1) infection appeared to be
      heralded by the infiltration of helper/inducer T cells.

PMID- 1374585
TI  - Comparison of an immunoperoxidase "sandwich" staining method and western blot
      detection of P-glycoprotein in human cell lines and sarcomas.
AB  - The applicability of a multilayer immunoperoxidase "sandwich" method (IpS)
      developed by Chan14 for the amplified detection of P-glycoprotein (Pgp) was
      investigated. The authors examined 15 formalin-fixed cell lines, as well as
      formalin-fixed, paraffin-embedded sections from single biopsies of 46 sarcomas.
      The cell lines included sensitive and multidrug resistant sublines (KB, A2780,
      MCF-7, HeLa) with various relative degrees of resistance to doxorubicin (Dox).
      The sarcoma biopsy specimens were selected on the basis of the results obtained
      in Western blot (WB) detection of Pgp (22 positive and 24 negative by WB) using
      C219 and C494 monoclonal antibodies to Pgp. The IpS method employed C219. The
      least resistant cell line in which Pgp could be detected by IpS was fivefold
      resistant to doxorubicin, whereas Pgp was detected by WB in cells greater than
      twofold resistant. Cell lines having greater than fivefold resistance to Dox were
      positive by both IpS and WB analyses. The less resistant cell lines contained
      more nonreactive cells whereas the highly resistant cell lines showed more
      homogeneous strong membrane reactions. Among the six cell lines determined to be
      Pgp negative by WB analysis, no false positive immunostaining by IpS existed. One
      of 22 WB positive and 7 of 24 WB-negative sarcoma biopsy specimens were positive
      by IpS methods. Reaction varied and was always focal (a minimum of 3-5 cells,
      ranging up to 3-4 high power fields) indicating pronounced heterogeneous
      distribution of Pgp. Thus, WB can detect low average (overall) levels of Pgp in
      tumor samples but such low concentrations of PgP at the single cell are not
      detectable by IpS methods. However, IpS can discern among many Pgp-negative cells
      small subpopulations of immunoreactive cells, which are not detected by WB
      analysis due to Pgp dilution by the membrane protein of numerous Pgp negative
      cells. IpS and WB used together as complementary methods can provide more
      complete information about Pgp distribution and content, particularly in the case
      of heterogeneous human tumors. The IpS method is more suitable for less
      drastically treated (not embedded) cell line specimens than for paraffin-embedded
      (routine) sections. Some modification of the present IpS protocol seems necessary
      to increase its sensitivity and reduce the disparity with WB results.

PMID- 1374586
TI  - Immunohistochemical identification of cytotoxic lymphocytes using human perforin
      monoclonal antibody.
AB  - Perforin is a potent cytolytic pore-forming protein expressed in cytoplasmic
      granules of cytotoxic T lymphocytes and natural killer cells. A new monoclonal
      antibody raised against human perforin was used to detect both in vitro and in
      vivo perforin expression in cytotoxic cells. Immunohistochemical analysis of
      human peripheral blood mononuclear cells cultured in recombinant interleukin-2
      (rIL-2) showed strong granular cytoplasmic staining of the IL-2 activated
      cytotoxic cells. Fresh-frozen tissue sections from patients with heart allograft
      rejection were also stained. Strong granular cytoplasmic staining of the
      mononuclear inflammatory infiltrate characteristic for perforin in cardiac
      allograft rejection was observed. The detection and quantitative analysis of
      perforin-associated cytotoxic cells by the human anti-perforin monoclonal
      antibody will help to evaluate the significance of these functionally distinct
      cytotoxic cells in human tissue.

PMID- 1374588
TI  - Expression of vascular cell adhesion molecule-1 in fibroblastlike synoviocytes
      after stimulation with tumor necrosis factor.
AB  - Rapid expression of mRNA encoding vascular cell adhesion molecule-1 (VCAM-1) was
      induced by tumor necrosis factor (TNF) in fibroblast-like cells obtained from
      synovial tissue. Both alternatively spliced forms of VCAM-1 mRNA were detected by
      polymerase chain reaction in TNF-stimulated fibroblast-like synoviocytes. Western
      blotting analysis showed that two distinct proteins, reactive with an anti-VCAM-1
      anti-sera, were expressed by 2 hours of TNF stimulation in both synoviocytes and
      human umbilical cord vein endothelial cells (HUVEC). The majority of HUVEC and
      synoviocytes displayed VCAM-1 surface expression after several hours of TNF
      stimulation. In contrast, dermal fibroblasts upregulated intercellular adhesion
      molecule-1 (ICAM-1) but not VCAM-1 expression in response to TNF. These results
      indicate that VCAM-1 and ICAM-1 expression can be differentially regulated and
      suggest tissue specific regulation of VCAM-1 expression. Furthermore, these
      findings may provide an explanation for the chronic retention and activation of
      long-lived lymphocytes and monocytes, which express VLA-4 (the receptor for VCAM
      1), in the synovium in rheumatoid arthritis.

PMID- 1374587
TI  - Persistent complement activation on tumor cells in breast cancer.
AB  - The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S
      protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of
      breast cancer and on 6 samples of benign breast tumors using polyclonal or
      monoclonal antibodies and the streptavidin-biotin-peroxidase technique. All the
      tissue samples with carcinoma in each the TNM stages presented C5b-9 deposits on
      the membranes of tumor cells, thin granules on cell remnants, and diffuse
      deposits in the necrotic areas. When chemotherapy and radiation therapy preceded
      surgery, C5b-9 deposits were more intense and extended. The C5b-9 deposits were
      absent in all the samples with benign lesions. S-protein/vitronectin was present
      as fibrillar deposits in the connective tissue matrix and as diffuse deposits
      around the tumor cells, less intense and extended than fibronectin. IgG, C3, and
      C4 deposits were present only in carcinoma samples. The presence of C5b-9
      deposits is indicative of complement activation and its subsequent pathogenetic
      effects in breast cancer.

PMID- 1374589
TI  - A novel monoclonal antibody to cytokeratin 18 with reactivity toward lung
      squamous cell carcinomas and adenocarcinomas of various sites.
AB  - Antibodies to cytokeratins (CKs) have found extensive application in the
      differential diagnosis of epithelial tumors. The chain-specific anti-CK reagents
      appear to be of practical value for further subtyping of carcinomas. The authors
      have produced a novel anti-CK 18 monoclonal antibody (ACK-156) using a modified
      immunization procedure that included sequential injections of human epidermal
      keratin, cyclophosphamide, and enriched cytoskeletal extracts from a human lung
      carcinoma cell line. This protocol effectively amplified clones with reactivity
      toward CK epitopes not present in epidermal keratin. Monospecificity of the
      antibody was confirmed by immunoblot analysis using both total cell lysates and
      cytoskeletal extracts as antigens. Immunoperoxidase staining of adenocarcinomas
      from a variety of sites, including lung, was strongly positive. Squamous cell
      carcinomas of lung were also strongly stained whereas squamous cell carcinomas of
      head and neck origin were stained focally or not at all. In contrast, several
      commercially available anti-CK 18 monoclonal antibodies did not distinguish
      squamous cell carcinomas of lung from those of head and neck origin. Immunoblot
      analysis of tumor lysates corroborated the tissue staining results and revealed
      that the commercially available antibodies that were tested recognize at least
      one other low molecular weight peptide in addition to the CK 18 peptide
      recognized by ACK-156.

PMID- 1374590
TI  - Expression of the bcl-2 gene product in follicular lymphoma.
AB  - Expression of bcl-2 protein was analyzed in 140 cases of follicular lymphoma by
      immunohistologic staining of paraffin-embedded tissue; 85% of cases were
      positive, the frequency being related to histologic grade (100% for the small
      cleaved cell type, 86% for the mixed cell type, and 76% for the large cell
      group). There was striking heterogeneity of bcl-2 content in a number of cases
      and the smaller neoplastic cells (i.e., centrocytes) were usually the most
      strongly labeled. In most cases, bcl-2 protein staining was much weaker in normal
      lymphoid cells than in the neoplastic cells. In several cases, staining for bcl-2
      revealed patterns of neoplastic cell spread into adjacent tissue (e.g., normal
      follicles, lymphoid sinuses), and bcl-2 protein expression tended to be highest
      in these migratory cells.

PMID- 1374591
TI  - Disruptions of muscle fiber plasma membranes. Role in exercise-induced damage.
AB  - The authors have tested the hypothesis that plasma membrane disruptions are an
      early form of structural damage to the fibers of eccentrically exercised muscle.
      Rat serum albumin (RSA) was used as a marker for muscle-fiber wounding in the rat
      tricep (medial head) exercised eccentrically by downhill running. In all muscles
      examined, strong staining with a horseradish peroxidase (HRP)-conjugated anti-RSA
      antibody was observed between fibers (intercellular staining) and also within
      certain fibers (intracellular staining). This intracellular staining was
      interpreted as identifying muscle fibers wounded at their plasma membranes and
      hence rendered transiently or permanently permeable to extracellular RSA. The
      most striking finding of this study was a 6.9-fold increase relative to
      unexercised controls in the number of wounded cells in the medial head
      immediately after eccentric exercise. The authors also reproducibly observed,
      albeit less frequently, myocytes that stained with anti-RSA in the medial head
      and several other muscles of the "unexercised," caged laboratory rat. The extreme
      vulnerability of muscle plasma membranes to mechanically induced stress was
      revealed in this study by HRP injections into the triceps long head. A single
      injection of 200 microliters HRP through a 26-gauge needle resulted in extensive
      labeling of the muscle fibers present in the long head cross-sectioned at the
      injection site. The authors propose that initially resealable and/or highly
      localized, unsealable membrane wounds are an early form of exercise-induced
      damage that could progress along the length of the fiber until, 1 to 4 days after
      eccentric exercise, it becomes sufficiently severe that it can be readily
      recognized as the frank fiber necrosis and cellular infiltration described in
      numerous previous studies. In possessing cells wounded at their plasma membranes,
      normal, undisturbed rat muscle and eccentrically exercised muscle appears to
      resemble gut and skin, two additional tissues routinely exposed to mechanical
      forces in vivo. The authors propose that membrane disruptions provide a route
      into and out of myofiber cytoplasm distinct from the conventional, membrane
      bounded routes of endo- and exocytosis, and therefore may be of importance both
      technically, as a route for introducing foreign genes into muscle cells, and
      biologically, as a route for release of the growth factor, basic fibroblast
      growth factor.

PMID- 1374592
TI  - DNA ploidy abnormalities in the liver of children with hereditary tyrosinemia
      type I. Correlation with histopathologic features.
AB  - Hereditary tyrosinemia (HT) is an autosomal recessive disorder of tyrosine
      metabolism that results in cirrhosis and hepatocellular carcinoma early in life,
      and that may be a useful model of early malignant transformation. This is the
      first report of DNA ploidy in this disease. The authors studied formalin-fixed
      liver tissue in three cases (two chronic and one acute) of HT for the presence of
      DNA aneuploidy by flow cytometric (FCM) analysis and image analysis (IA). In the
      chronic cases, the authors found DNA aneuploidy by FCM in 2/20 cirrhotic nodules
      in one case and 1/21 tissue sections in the other. Questionable minor aneuploid
      peaks were detected by FCM in 2/20 and 2/21 sections in these two cases,
      respectively. Static DNA measurements by IA were performed on those sections
      having abnormal histograms as well as in some sections having diploid DNA
      distribution. By this method, the authors confirmed the results of FCM studies
      and found additional small aneuploid nodules not detected by FCM, frequently
      associated with various forms of hepatocellular dysplasia as well as steatosis.
      In one case of acute HT (autopsy), no definite aneuploid peaks were present in
      five blocks. By immunohistochemical analysis, the authors found frequent positive
      staining for alpha-fetoprotein (AFP) in the cirrhotic nodules of the two chronic
      cases as well as in the steatotic regenerative nodules of the acute case. The
      expression of AFP may represent disturbed regeneration and maturation of liver
      cells in this disease. This study shows that DNA ploidy may be a useful marker
      for early malignant transformation in HT and supports the preneoplastic nature of
      the hepatocellular dysplasia in this disease.

PMID- 1374593
TI  - Early microvascular changes in murine cerebral malaria detected in retinal
      wholemounts.
AB  - Changes in the cerebral microvasculature such as breakdown of the blood-brain
      barrier, petechial hemorrhages, congestion, and edema are observed in the later
      stages of murine cerebral malaria. These changes have been described from
      histologic sections of brain, but the need to section the material makes direct
      observation of the microvasculature in situ difficult. The retinal vasculature,
      in contrast, offers a unique opportunity to study rheologic, barrier, and
      functional properties of the microvasculature as a wholemount preparation with
      normal spatial relationship with other tissues and as an intact vascular plexus.
      A combination of techniques, including intravascular perfusion of Evan's Blue,
      Bisbenzimide and Monastral Blue, and fluorescence and transmitted light
      observation of retinal wholemounts, were developed to examine the progressive
      microvascular changes in murine cerebral malaria. These techniques allowed
      detection of phenomena such as monocyte adherence to endothelial cells,
      congestion, small hemorrhages, and breakdown of the blood-retinal barrier, with
      details of the location of this leakage, earlier than was possible by studying
      brain sections. Because the retina is intact, the phenomena were seen in greater
      detail and some, such as occlusion of vessel segments, were detectable only in
      retinal wholemounts. In addition, the covisualization of the blood elements,
      barrier properties, and vascular endothelial integrity that are possible with
      retinal wholemounts allowed detailed analysis of the interaction of different
      cellular elements in the pathogenesis of cerebral malaria. Except for detection
      of edema, the retinal wholemount technique offers a more powerful and less time
      consuming technique for detecting early microvascular changes in murine cerebral
      malaria. This technique could find wider application in the study of other
      diseases that affect the microvasculature of the central nervous system, such as
      experimental allergic encephalitis and meningitis.

PMID- 1374595
TI  - Correlates of maternal directiveness with children who are developmentally
      delayed.
AB  - Interactions between 25 mothers and their children with developmental delays were
      correlated to determine the relationships between maternal directiveness and a)
      maternal behavior regarded as developmentally facilitative, b) maternal
      intrusiveness, and c) child developmental competence and behavioral engagement.
      The findings, many of which challenge common conceptions about the nature and
      role of maternal directiveness, are discussed in relation to these conceptions
      and to the potential role of directiveness in the development of children with
      handicaps.

PMID- 1374596
TI  - Comparison of the effect of ELF on total RNA content in normal and transformed
      human cells.

PMID- 1374594
TI  - A shared epitope in the acetylcholine receptor-alpha subunit and fast troponin I
      of skeletal muscle. Is it important for myasthenia gravis?
AB  - The monoclonal antibody MAb 155, isolated by Tzartos et al, recognizes the alpha
      subunit of acetylcholine receptor (AChR) and stains type II skeletal muscle
      fibers but does not decorate heart muscle. In addition it reacts with most
      myasthenia gravis-associated thymomas. The authors show by immunoblotting
      techniques that the myofibrillar antigen is a 23 kd protein and by partial
      protein sequence data identify it as fast troponin I. Fast troponin I from
      various species contains the sequence EEKSGMEGRK close to the C-terminal end at
      positions 165 to 174. The first lysine (K) is crucial for MAb 155 reactivity
      since its substitution by methionine and leucine in slow troponin I and cardiac
      troponin I, respectively, abolishes MAb 155 reactivity. The epitope identified on
      troponin I is homologous in sequence with the MAb 155 epitope on the AChR alpha
      subunit established by direct peptide binding as KSAIEGIK (positions 373-380).
      The authors consider whether fortuitously shared epitopes can be responsible for
      the high level of autoantibodies to AChR and to muscle proteins seen in many MG
      patients.

PMID- 1374597
TI  - Protective effects of vitamin E against bleomycin-induced genotoxicity in head
      and neck cancer patients in vitro.
AB  - The quantitative protective effects of alpha-tocopherol acid and alpha-tocopherol
      acid succinate on mutagen-induced genotoxicity were studied in human
      lymphoblastoid cell lines and lymphocytes from cultures of peripheral blood. Both
      agents showed a dose-dependent protection both in lymphoblastoid cell lines and
      in lymphocytes of head and neck cancer patients. The concentrations used were in
      the phatmacologic concentration range of vitamin E. The protection against
      genetic toxic effects may be an important part of the cancer-protective effects
      of vitamin E.

PMID- 1374598
TI  - Study of multidrug resistance (mdr1) gene in non-small-cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) is one of the tumors that shows intrinsic drug
      resistance to various chemotherapeutic agents. We investigated a possible role of
      the multidrug resistance (mdr1) gene amplification using a DNA slot blot analysis
      in 23 untreated non-small-cell lung cancer tissues and 14 corresponding adjacent
      normal lung tissue samples. In all instances, whether tumors or adjacent normal
      tissue samples, DNA amplification was not detected except in 1 adenocarcinoma and
      2 squamous cell carcinomas that had a low level of amplification of mdr1 gene. In
      addition, 6 untreated tumors and 7 normal tissue samples were examined for mdr1
      RNA expression using RNA slot blot analysis. Only low levels of mdr1 expression
      were observed in all cases. We conclude that mechanisms other than mdr1
      amplification or expression account for the intrisic drug resistance of non-small
      cell lung cancers.

PMID- 1374599
TI  - Induction of karyological damage by bleomycin in polyploidizating rabbit
      hepatocytes.
AB  - The effects of the antitumor drug bleomycin on polyploidizating hepatocytes of
      immature rabbits were investigated by combining cytochemical (static
      microfluorometry) and morphological (fluorescence and electron microscopy)
      approaches. In addition to a decelerating effect of the drug on the cell
      kinetics, there were several types of karyological damage (micronuclei,
      internuclear chromatin bridges, mitotic chromosome bridges), thus demonstrating a
      clastogenic activity of bleomycin on the DNA, Moreover, anomalous nuclear and
      cytoplasmic divisions suggest interference of the drug with other cellular
      structures (mainly the microtubule network) responsible for the cell kinetics.

PMID- 1374600
TI  - Therapeutic approaches to hemoglobin switching in treatment of
      hemoglobinopathies.
AB  - The past decade has witnessed profound increases in knowledge of the structure,
      function, and developmental regulation of the human globin genes. This
      information has deepened our understanding of the molecular and cellular
      mechanisms underlying inherited disorders affecting hemoglobin, and it has
      provided a new perspective for attaining meaningful increases in fetal hemoglobin
      synthesis in the management of sickle cell anemia and beta thalassemia. Efforts
      to provide therapy for these disorders are based on three factors: an
      understanding of their pathophysiology; the potential for fetal hemoglobin to
      alter its manifestation; and the concept that developmental changes in globin
      gene expression might be reversed by manipulating cellular and molecular
      regulatory mechanisms. In this review we discuss these topics and examine
      critically recent efforts to apply various pharmacological agents to in vitro,
      animal, and human models with the goal of increasing HbF synthesis. Several
      agents have demonstrated activity in patients with hemoglobin disorders. One such
      agent, hydroxyurea, has been shown to be potentially efficacious in phase II
      clinical trials in patients with sickle cell anemia and awaits testing in a
      placebo-controlled phase III study.

PMID- 1374601
TI  - Antithrombins: their potential as antithrombotic agents.
AB  - The inhibition of thrombin is the key to the prevention and treatment of
      thrombotic disorders. Although heparin is an extremely effective anticoagulant,
      it has certain limitations that are not shared by newer thrombin inhibitors. As a
      result, these novel inhibitors may have advantages over heparin in certain
      clinical settings.

PMID- 1374602
TI  - [Nuclear DNA analysis of the carcinoma cells of periampullary region using
      cytologic bile specimen].

PMID- 1374603
TI  - Fetal haemoglobin and early manifestations of homozygous sickle cell disease.
AB  - The relevance of fetal haemoglobin (HbF) concentration to the development of
      early clinical manifestations of homozygous sickle (SS) disease has been
      investigated by examining the time to first occurrence and the proportional
      hazard of these complications in three groups of the HbF distribution at age 5
      years. HbF was significantly related to dactylitis, painful crises, acute chest
      syndrome, and acute splenic sequestration. The relationship suggested that a
      critically low HbF concentration increased the risk, little difference in risk
      occurring between the medium and high HbF groups. The abdominal painful crisis
      and hypersplenism were not related to HbF concentration suggesting that the
      degree of sickling may not be important in their genesis. Parental education on
      acute splenic sequestration should be focused on children with HbF concentrations
      in the lowest part of the HbF distribution for age.

PMID- 1374605
TI  - [Neurectodermal malignant tumor of the soft tissues after treatment with
      immunosuppressive agents of lipoid nephrosis].
AB  - Immunosuppressive drugs are known to increase the risk of inducing neoplasia,
      especially acute leukaemia when high doses are used. A case of nephrosis in a 10
      year-old boy treated with chlormethine (cumulative dose: 0.8 mg/kg) and
      chlorambucil (cumulative dose: 10 mg/kg) is reported. Four years after the
      beginning of the treatment an extraskeletal Ewing's sarcoma occurred. Since the
      review of literature failed to find any malignancy induced by such an
      immunosuppressive treatment for nephrosis, the question whether or not this
      extraskeletal Ewing's sarcoma was attributable to this treatment remains
      unanswered.

PMID- 1374604
TI  - Peri- and postoperative changes in serum levels of four tumor markers and three
      acute phase reactants in benign and malignant gynecological diseases.
AB  - Serum levels of squamous cell carcinoma antigen, carcinoembryonic antigen, CA
      125, tissue polypeptide antigen, CRP, alpha 1-antitrypsin and haptoglobin were
      determined peri- and postoperatively in patients undergoing surgery for benign
      gynecological disease (n = 18) and postoperatively in women operated for cervical
      carcinoma (n = 23). The only significant changes seen after premedication, during
      anesthesia and during surgery were a decrease in serum concentrations of alpha 1
      antitrypsin and haptoglobin. We found no postoperative changes in the serum
      levels of squamous cell carcinoma antigen nor in carcinoembryonic antigen values.
      However, the latter analyte was influenced by smoking habits. Elevated levels of
      CA 125 and tissue polypeptide antigen were found in the cancer patients,
      predominantly within the first 1-3 weeks after surgery. These levels decreased to
      normal values within 4-6 weeks postoperatively. The median intraindividual
      coefficients of variation for the tumor markers ranged between 15% and 28% in 30
      control women not having surgery. In general, it would seem advisable to wait 6
      weeks after surgery before monitoring with CA 125 and TPA is started.

PMID- 1374606
TI  - [Recent advances in pedopsychiatry].

PMID- 1374607
TI  - 5.1 H11 (neural cell adhesion molecule) immunostaining of normal tissues.

PMID- 1374608
TI  - Choroidal neovascularization associated with choroidal hemangiomas.
AB  - Two patients with choroidal hemangiomas developed choroidal neovascularization.
      One patient with Sturge-Weber syndrome, a unilateral diffuse choroidal
      hemangioma, and a serous detachment of the macula was treated with yellow dye
      laser photocoagulation in a grid pattern to the tumor before glaucoma filtration
      surgery. Four years after successful laser treatment, the patient developed
      subfoveal choroidal neovascularization in an area of treatment. A second patient
      with a circumscribed choroidal hemangioma developed spontaneous subfoveal
      choroidal neovascularization 12 years after initial diagnosis of the hemangioma.
      The development of choroidal neovascularization associated with choroidal
      hemangiomas represents a potential cause of poor visual outcome in these
      patients.

PMID- 1374609
TI  - Expression of cell adhesion molecules in posterior uveitis.
AB  - Cells in the eye express surface molecules that direct leukocyte migration during
      ocular inflammation. We studied the expression of intercellular adhesion molecule
      1, lymphocyte function-associated antigen-1, and endothelial leukocyte adhesion
      molecule-1 in six enucleated eyes from patients with uveitis and in seven normal
      control eyes. Lymphocyte function-associated antigen-1 was expressed on
      infiltrating lymphocytes and intercellular adhesion molecule-1 was expressed on
      endothelial cells of retinal and choroidal blood vessels and the retinal pigment
      epithelium in all uveitic eyes, but in none of the normal control eyes. Ocular
      inflammatory cells stained strongly positive for tumor necrosis factor alpha in
      all eyes with uveitis, but four of six uveitic eyes showed mild staining for
      tumor necrosis factor beta and interferon gamma. Cell adhesion molecules are
      expressed in eyes with posterior uveitis and may be regulated by cytokines such
      as tumor necrosis factor alpha.

PMID- 1374610
TI  - [Malacoplakia or pseudo Whipple's disease? Report of a case of bronchial
      granuloma in a patient with AIDS].

PMID- 1374611
TI  - Roll, roll, roll your leucocyte gently down the vein....
AB  - The rapid advances being made in unravelling the biochemistry and function of the
      three categories of adhesion molecule involved in leucocyte-endothelial-cell
      interactions, namely selectins, integrins and the Ig super-family molecules, were
      highlighted at a recent meeting. In this short report, Nancy Hogg describes these
      developments and the prospects for anti-adhesion molecule therapy in the clinic.

PMID- 1374612
TI  - The mechanism of action of cyclosporin A and FK506.
AB  - CsA and FK506 are powerful suppressors of the immune system, most notably of T
      cells. They act at a point in activation that lies between receptor ligation and
      the transcription of early genes. Here, Stuart Schreiber and Gerald Crabtree
      review recent findings that indicate CsA and FK506 operate as prodrugs: they bind
      endogenous intracellular receptors, the immunophilins, and the resulting complex
      targets the protein phosphatase, calcineurin, to exert the immunosuppressive
      effect.

PMID- 1374613
TI  - Cardiovascular effects of intrathecal administration of substance P in the rat:
      interactions with serotonergic mechanisms.
AB  - Intrathecal (i.th.) administration of substance P (SP, 6.5 nmol) at the Th 8-10
      level in conscious rats increased blood pressure (carotid artery), heart rate and
      plasma catecholamine concentrations. The responses were antagonized by the
      intravenous (i.v.) but not i.th. pretreatment with the 5-HT2-receptor antagonists
      ketanserin and ritanserin and intrathecally administered serotonin (5-HT, 10
      micrograms). The pressor response and the increase in plasma noradrenaline
      concentrations were also antagonized by i.v. or i.th. pretreatment with the 5
      HT1A-agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). In contrast the
      pressor response to SP was facilitated by the 5-HT1A-antagonist 1-pindolol (i.v.
      or i.th). Pretreatment with SP (i.th) reduced the hypotensive response to i.v. 8
      OH-DPAT. These results demonstrate functional interactions between SP and
      serotonergic mechanisms in the central system, but the precise location and
      nature were not elucidated.

PMID- 1374614
TI  - Evidence for post-transcriptional regulation of cytokeratin gene expression in a
      rat liver epithelial cell line.
AB  - T51B, a cell line of the rat liver nonparenchymal cell compartment, contains a
      cytokeratin (CK) pair composed of CK8, a CK typical of simple epithelium, and
      CK14, a CK usually present in proliferative stratified epithelium. T51B-Ni, a
      subclone selected by prolonged exposure of the parental clone to nickel
      subsulfide contains CK8 and CK18 (its usual partner in simple epithelium), as
      well as CK14, at a lower level. The two clones have comparable levels of
      vimentin. Northern blot analyses of cytoplasmic mRNA demonstrated that the
      differences in the steady state mRNA levels of each CK paralleled those observed
      at the protein level, thus showing that the regulatory events occurred prior to
      translation. The most prominent difference was a 30-fold higher level of CK18
      mRNA in T51B-Ni cells. Run-off assays of isolated nuclei revealed that the level
      of CK8, CK14, and vimentin was regulated primarily at the transcriptional level.
      However, the large increase in CK18 mRNA levels in T51B-Ni cells did not result
      from a corresponding increase in the relative level of CK18 gene transcription
      nor from a change in cytoplasmic CK18 mRNA stability. Comparative Northern blot
      analyses of nuclear and cytoplasmic mRNAs further suggested that the control of
      CK18 gene expression in T51B cells is post-transcriptionally mediated by nuclear
      events.

PMID- 1374615
TI  - Intermediate filaments in rat ovarian surface epithelial cells: changes with
      neoplastic progression in culture.
AB  - Interrelationships between neoplastic progression and the expression of
      intermediate filaments were examined in primary cultures, immortal lines, and
      Kirsten murine sarcoma virus (KiMSV) transformed lines of rat ovarian surface
      epithelial (ROSE) cells. Immunofluorescence microscopy revealed abundant keratin
      filaments in all cells of primary cultures. In immortal, nontumorigenic lines,
      keratin filaments were detected in fewer cells, in smaller numbers, and in
      microscopically altered forms. The percentage of keratin-positive cells ranged
      from 4 to 54%. Its expression was inversely proportional to cell density. Keratin
      expression was similar in the two immortal lines, although one had retained a
      monolayered epithelial growth pattern resembling primary cultures, while in the
      other the growth pattern of the cells was more atypical. The two KiMSV
      transformed lines were previously shown to produce tumors in vivo that resemble
      human ovarian endometrioid stromal sarcomas. In spite of this histologic
      appearance, the proportion of keratin-positive cells in these cells was increased
      over the immortal lines. Keratin expression was unrelated to cell density, and
      keratin in most virally transformed cells was limited to few, fine filaments. In
      thymidine-labelled immortal and virus-transformed cultures stained for keratin,
      no correlation was found between keratin expression and proliferative activity.
      The keratin profiles of primary and immortal cultures were identical on Western
      blots, with subtypes ranging from 52 to 66 kDa. The two virally transformed lines
      lacked some of the subtypes. Vimentin networks were faint or absent in primary
      cultures. In the immortal and the virus-transformed lines, neoplastic progression
      was associated with increasing vimentin expression but with no changes in
      filament morphology and distribution. The results show that the abnormalities in
      intermediate filament expression that accompany immortalization do not preclude
      the retention of a normal epithelial morphology and growth pattern in this cell
      type. Furthermore, the number of intermediate filaments and their intracellular
      distribution appear to be altered at an earlier stage in neoplastic progression
      than those mechanisms that select for specific keratin subtypes, or those that
      respond to regulation by cell density. Finally, the presence of keratin in the
      KiMSV-transformed lines examined in this study supports the hypothesis that human
      ovarian stromal sarcomas can arise in the OSE.

PMID- 1374616
TI  - Structural characterization of the O-polysaccharide of the lipopolysaccharide
      produced by Salmonella milwaukee O:43 (group U) which possesses human blood group
      B activity.
AB  - The O-polysaccharide of the lipopolysaccharide produced by Salmonella milwaukee
      O:43 (group U) was shown by composition analysis, methylation, periodate
      oxidation, and 1H and 13C nuclear magnetic resonance spectroscopic analytical
      methods to be a polymer of branched pentasaccharide repeating units having the
      structure: [formula: see text] The blood-group activity of the O-polysaccharide
      was established by its serological reactivity with a specific monoclonal antibody
      to human blood group B, using passive hemagglutination and ELISA assays,
      indicating the common antigenic epitope to be a nonreducing terminal
      trisaccharide unit composed of L-Fucp and D-Galp (1:2) residues.

PMID- 1374617
TI  - Structure and function of L-selectin.
AB  - The selectins are a newly described family of carbohydrate-binding adhesion
      molecules involved in the regulation of leukocyte traffic. Selectins are composed
      of an N-terminal C-type lectin domain, a single EGF domain, a variable number of
      short consensus repeat (SCR) domains, a transmembrane region and a cytoplasmic
      tail. L-selectin (LAM-1/LECAM-1/LECCAM-1) is the only selectin expressed on
      leukocytes, and mediates a number of leukocyte-endothelial interactions,
      including the binding of lymphocytes to HEV of peripheral lymph node high
      endothelial venules (HEV), neutrophil rolling, and leukocyte attachment to
      cytokine-treated endothelium in vitro. Stable transfectants expressing a series
      of chimeric selectins and deletion mutants were functionally analyzed in order to
      determine the molecular basis of adhesion mediated by L-selectin. The specificity
      of adhesion was found to reside entirely within the lectin domain, suggesting
      that this domain is the only domain of the protein to interact with the
      carbohydrate ligand. These results make previous observations that certain mAbs
      which block function map to each of the extracellular domains difficult to
      interpret. In addition, deletion of the cytoplasmic tail of L-selectin abolished
      adhesion, without affecting ligand recognition. Thus, each domain of the
      selectins has an important, but distinct, role in cell adhesion.

PMID- 1374618
TI  - Sympathetic nerve contact alters membrane resistance of cells of the RBL-2H3
      mucosal mast cell line.
AB  - Indirect evidence links sensory nerves with mast cells (MC) in inflammatory
      reactions of airway, skin, and intestine. Isolated MC secrete histamine,
      serotonin, and other inflammatory mediators in response to neuropeptides such as
      substance P (SP) in vitro. To obtain direct evidence of nerve/MC interactions, we
      used a tissue culture model involving the co-culture of murine sympathetic
      neurons and rat basophilic leukemia (RBL) cells (homologous to mucosal MC). An
      electrophysiologic analysis of the consequences of neuron/RBL cell contacts
      showed that neurite contact with RBL cells reduced the control input resistance
      (Ro) of 61.8 +/- 3.2 (n = 110) M omega to 22.4 +/- 4.8 (n = 13) M omega (P less
      than 0.01) without change in the membrane potential. Time course studies showed
      that Ro of RBL cells with neurite contact was always lower by 30 to 54% than
      adjacent RBL cells lacking such contact. This effect was not seen in RBL cells
      cultured on rat fibroblasts. Direct application of SP, bradykinin, and
      somatostatin, but not acetylcholine, noradrenaline, or the putative
      neurotransmitter ATP, could partly mimic the effect of neurite contact.
      Therefore, neurotransmitter release from sympathetic neurons in contact with RBL
      cells may decrease RBL cell membrane resistance, possibly leading to activation.

PMID- 1374619
TI  - [How to make slides].
AB  - Quality of oral presentation slides is based on content and design. The most
      common fault is presentation of slides with too much writing, or with type to
      small to be seen by the audience. With a few design rules and a minimum of
      photographic equipment, high quality slides are to be obtain. Slides are
      projected to be read and communicate an idea, make them nice, simple and
      readable; there is no need for fancy art works. Format and color are important
      but not the main point, and they will depend on available material, time and
      money.

PMID- 1374620
TI  - [The role of local excision in the treatment of rectal tumors].

PMID- 1374621
TI  - Phylogenetic relationships of three porcine mycoplasmas, Mycoplasma
      hyopneumoniae, Mycoplasma flocculare, and Mycoplasma hyorhinis, and complete 16S
      rRNA sequence of M. flocculare.
AB  - The nucleotide sequence of the 16S rRNA gene of Mycoplasma flocculare was
      determined and was compared with the sequence of a related porcine mycoplasma,
      Mycoplasma hyopneumoniae. While the overall level of DNA-DNA homology was
      approximately 11%, sequence alignment of the two 16S rRNA genes yielded a
      homology value of more than 95%, emphasizing the highly conserved nature of the
      16S rRNA gene. Multiple sequence alignments with other mollicutes indicated that
      M. flocculare, M. hyopneumoniae, and Mycoplasma hyorhinis form a subcluster
      within the fermentans phylogroup, and this subcluster is distinct from the
      Mycoplasma pneumoniae phylogroup. Thus, the three mycoplasmas isolated from
      porcine respiratory systems exhibit phylogenetic similarities.

PMID- 1374622
TI  - Phylogenetic relationships between the western aster yellows mycoplasmalike
      organism and other prokaryotes established by 16S rRNA gene sequence.
AB  - Restriction fragments containing the 16S rRNA gene of the western aster yellow
      mycoplasmalike organism (SAY-MLO) were identified in Southern blots probed with
      cloned fragments of the western X-disease mycoplasmalike organism 16S rRNA gene.
      Two fragments which contained the entire SAY-MLO 16S rRNA gene and flanking DNA
      were cloned in M13 and sequenced. The SAY-MLO 16S rRNA gene is approximately
      1,535 bp long, has a G+C content of 47 mol%, and has an overall secondary
      structure similar to that proposed for Escherichia coli. Putative rRNA promoter
      sequences and sequences involved in processing of the primary rRNA transcript
      were similar in the SAY-MLO, two Mycoplasma species, and Bacillus subtilis,
      suggesting that these prokaryotes and the mycoplasmalike organisms may have
      similar transcriptional and processing enzymes. We identified two tRNA genes, a
      tRNA(Tyr) (GTA) gene upstream from the 16S rRNA gene and a tRNA(Ile) (GAT) gene
      in the spacer region between the 16S and 23S rRNA genes. Comparisons of the SAY
      MLO 16S rRNA nucleotide sequence with 16S rRNA sequences of other organisms
      indicated that the SAY-MLO is phylogenetically related most closely to other
      plant-pathogenic mycoplasmalike organisms, followed by Anaeroplasma species,
      Acholeplasma species, and some Mycoplasma species.

PMID- 1374623
TI  - Mycobacterium confluentis sp. nov.
AB  - A new rapidly growing mycobacterium was isolated from human sputum. This organism
      grew at 22, 31, 37, and 41 degrees C and possessed catalase, acid phosphatase,
      acetamidase, urease, nicotinamidase, pyrazinamidase, and nitrate reductase
      activities. It did not produce nicotinic acid, hydrolyze Tween, or have
      benzamidase, isonicotinamidase, succinidamidase, and arylsulfatase activities. A
      mycolic acid analysis revealed a simple, unique pattern. The organism is
      susceptible to antituberculotic drugs. A comparative 16S rRNA sequence analysis
      placed this organism within the confines of the genus Mycobacterium, most closely
      related to the thermotolerant rapidly growing species. On the basis of the
      pattern of enzymatic activities and metabolic properties, as well as the unique
      16S rRNA sequence, we propose that our single strain represents a new species,
      for which we propose the name Mycobacterium confluentis. The type strain is
      strain 1389/90; a culture of this strain has been deposited in the German
      Collection of Microorganisms and Cell Cultures as strain DSM 44017.

PMID- 1374624
TI  - Comparative sequence analyses on the 16S rRNA (rDNA) of Bacillus acidocaldarius,
      Bacillus acidoterrestris, and Bacillus cycloheptanicus and proposal for creation
      of a new genus, Alicyclobacillus gen. nov.
AB  - Comparative 16S rRNA (rDNA) sequence analyses performed on the thermophilic
      Bacillus species Bacillus acidocaldarius, Bacillus acidoterrestris, and Bacillus
      cycloheptanicus revealed that these organisms are sufficiently different from the
      traditional Bacillus species to warrant reclassification in a new genus,
      Alicyclobacillus gen. nov. An analysis of 16S rRNA sequences established that
      these three thermoacidophiles cluster in a group that differs markedly from both
      the obligately thermophilic organisms Bacillus stearothermophilus and the
      facultatively thermophilic organism Bacillus coagulans, as well as many other
      common mesophilic and thermophilic Bacillus species. The thermoacidophilic
      Bacillus species B. acidocaldarius, B. acidoterrestris, and B. cycloheptanicus
      also are unique in that they possess omega-alicylic fatty acid as the major
      natural membranous lipid component, which is a rare phenotype that has not been
      found in any other Bacillus species characterized to date. This phenotype, along
      with the 16S rRNA sequence data, suggests that these thermoacidophiles are
      biochemically and genetically unique and supports the proposal that they should
      be reclassified in the new genus Alicyclobacillus.

PMID- 1374625
TI  - Phylogenetic analysis of the pathogenic anaerobe Clostridium perfringens using
      the 16S rRNA nucleotide sequence.
AB  - Clostridium perfringens, the first pathogenic clostridium examined, was placed in
      the nonmycoplasma subgroup of the low-dG+dC-content gram-positive cluster on the
      basis of the results of a phylogenetic analysis in which we used 16S rRNA
      comparisons. The closest relative that has been identified to date is Clostridium
      pasteurianum.

PMID- 1374626
TI  - Marrow proliferation and the appearance of giant neutrophils in response to
      recombinant human granulocyte colony stimulating factor (rhG-CSF).
AB  - During a study of recombinant human granulocyte colony stimulating factor (rhG
      CSF) administration, 15 patients received twice daily i.v. infusions and nine
      patients received daily s.c. infusions of rhG-CSF for 5 d prior to cytotoxic
      therapy, and then a second course subsequent to melphalan administration. There
      was a striking dose-related neutrophilia and the appearance in the blood of early
      myeloid cells that express the intercellular adhesion molecule CD54. In addition,
      giant neutrophils or macropolycytes were observed in the peripheral blood of all
      patients. These cells were evident on the display of the Technicon H*1 as a
      population of large peroxidase positive cells, and using Feulgen staining these
      cells were shown to be tetraploid. Bone marrow kinetics studies performed on Day
      4 or 5 indicated an increase in the proportion of bone marrow cells in S phase,
      G2 and mitosis, reflecting a proliferative response of the marrow. Large myeloid
      precursors and occasional binucleate promyelocytes were seen in the bone marrows
      done on Days 14 and 18 but not on Day 5. These findings indicate that
      administered G-CSF has both quantitative and qualitative effects on myeloid cells
      in vivo.

PMID- 1374627
TI  - Autotransplantation of peripheral blood stem cells mobilized by chemotherapy and
      recombinant human granulocyte colony-stimulating factor in childhood
      neuroblastoma and non-Hodgkin's lymphoma.
AB  - Seven children with advanced neuroblastoma and non-Hodgkin's lymphoma were
      treated with myeloablative chemoradiotherapy (180 mg/m2 melphalan plus 12 Gy
      fractionated total body irradiation), followed by autotransplantation of
      peripheral blood stem cells (PBSC). Sufficient PBSC to restore bone marrow
      function were collected by a small number of leukaphereses during haematopoietic
      recovery after chemotherapy and recombinant human granulocyte colony-stimulating
      factor (rhG-CSF). Furthermore, rapid recovery of neutrophils was found in all
      patients by the administration of rhG-CSF following transplantation: median 10 d
      (range 8-12) to attain more than 0.5 x 10(9)/l neutrophils, and 27 d (range 14
      73) to attain more than 50 x 10(9)/l platelets, respectively. Haematopoietic
      reconstitution has been maintained throughout the follow-up period (median 15
      months; range, 6-22). Peripheral blood stem cells mobilized by chemotherapy and
      rhG-CSF can induce complete haematopoietic reconstitution after myeloablative
      chemoradiotherapy.

PMID- 1374628
TI  - Endogenous platelet fibrinogen: its modulation after surface expression is
      related to size-selective access to and conformational changes in the bound
      fibrinogen.
AB  - Platelet stimulation results in the release of endogenous platelet fibrinogen
      which binds to the platelet surface. Previous studies have demonstrated that
      plasma fibrinogen bound to activated platelets becomes inaccessible to a variety
      of probes. We have studied endogenous platelet fibrinogen binding to activated
      platelets by employing an immunopurified polyclonal anti-fibrinogen antibody and
      F26, a monoclonal anti-fibrinogen antibody, which recognizes fibrinogen only when
      it is bound to a surface. Employing the Ig or F(ab')2 of the poly- or monoclonal
      antibody we found a marked decrease of fibrinogen accessibility 30-60 min after
      platelet activation. In contrast, platelet-bound fibrinogen remains accessible to
      the Fab fragment of F26 at a constant level for 30 min and increases at 60 min.
      The reduction of the polyclonal Fab fragment binding at 30 and 60 min is similar
      to the F26 Ig. These results indicate that the decreased accessibility of bound
      fibrinogen is related to two mechanisms; (1) that the access route to fibrinogen
      in size selective for the antibody probes and only small antibody probes, e.g.
      Fab fragments, can gain access to fibrinogen and (2) fibrinogen undergoes a
      conformational change(s) after binding which exposes at least one neo-epitope in
      the D domain of fibrinogen and which may decrease or mask the reactivity of other
      fibrinogen domains. Only the F26 Fab probe has full access to and identifies
      fibrinogen present on the platelet surface 60 min after stimulation.

PMID- 1374629
TI  - Two distinct patterns of glycosylphosphatidylinositol (GPI) linked protein
      deficiency in the red cells of patients with paroxysmal nocturnal
      haemoglobinuria.
AB  - We have studied three glycosylphosphatidylinositol (GPI) linked proteins on the
      erythrocytes of 14 patients with paroxysmal nocturnal haemoglobinuria (PNH). The
      pattern observed was bimodal in 12 of the patients and trimodal in two. Ten
      patients had a red cell population with normal CD59 antigen (membrane inhibitor
      of reactive lysis, MIRL), decay accelerating factor (DAF or CD55) and lymphocyte
      function-associated antigen (LFA-3 or CD58) and a second abnormal PNH population
      with absent CD59 antigen, DAF and LFA-3. The other two patients with a bimodal
      pattern had a red cell population with normal CD59 antigen, DAF and LFA-3 and an
      abnormal population with reduced, but not absent, CD59 antigen and DAF. The LFA-3
      on the abnormal red cells in these two patients appeared to be only slightly
      reduced. The two patients with a trimodal pattern had a normal population, a
      population with reduced, not absent, CD59 antigen and DAF, and a population with
      complete absence of CD59 antigen, DAF and LFA-3. The accuracy of the Ham test in
      estimating the proportion of red cells with the PNH defect in the two types of
      PNH was assessed. The case of one patient who appeared to be 'rescued' from
      severe aplastic anaemia by the development of PNH is described.

PMID- 1374630
TI  - Trilineage recovery by combination therapy with recombinant human granulocyte
      colony-stimulating factor (rhG-CSF) and erythropoietin (rhEpo) in severe aplastic
      anaemia.

PMID- 1374631
TI  - Emperipolesis of neutrophils by megakaryocytes and thrombocytopenia observed in a
      case of Kostmann's syndrome during intravenous administration of high-dose rhG
      CSF.

PMID- 1374632
TI  - Childhood polyclonal T cell lymphocytosis with neutropenia: effects of
      antilymphocyte globulin and granulocyte colony stimulating factor in vitro and in
      vivo.
AB  - The pathogenesis of the neutropenia that occurs in some patients with chronic T
      cell lymphocytosis is not well understood. We have investigated a 15-year-old
      girl with this syndrome. Initial committed bone marrow progenitor numbers (CFUgm)
      were low but markedly increased in vitro following T cell depletion. Similarly a
      transient correction of neutropenia was observed following in vivo lymphocyte
      depletion with antilymphocyte globulin. A sustained neutrophil recovery was
      achieved with daily therapy using recombinant human granulocyte colony
      stimulating factor (rhG-CSF) despite persistence of the lymphocytosis; during
      successful therapy CFUgm numbers remained low, and were not increased by the in
      vitro addition of rhG-CSF. These observations suggest the possibility of an
      inhibitory regulatory mechanism specifically acting on neutrophil granulopoiesis.

PMID- 1374633
TI  - Rapid identification by denaturing gradient gel electrophoresis of mutations in
      the gamma-globin gene promoters in non-deletion type HPFH.
AB  - We have outlined a fast, non-radioactive strategy to identify point mutations in
      the 5' flanking region of the gamma-globin genes using denaturing gradient gel
      electrophoresis (DGGE) of amplified DNA. In a sample of previously characterized
      carriers of non deletion-type hereditary persistence of fetal haemoglobin (HPFH)
      the different point mutations in both gamma gene promoters could be easily
      identified by DGGE of a 327 bp fragment. A 4 bp deletion at position -225 to -222
      of the A gamma globin gene was unexpectedly found in several samples and shown to
      represent a frequent polymorphism. Analysis of a 681 bp fragment specific for the
      5' region of the A gamma gene, showed that this can be used to determine the
      haplotype of the chromosome under study. This technique may be useful in the
      study of sequence variations associated with high Hb F expression in
      physiological and pathological conditions.

PMID- 1374635
TI  - Successful treatment of clozapine induced agranulocytosis with granulocyte-colony
      stimulating factor (G-CSF).

PMID- 1374634
TI  - Ki-1 lymphoma producing G-CSF.

PMID- 1374636
TI  - Accelerated recovery from drug-induced agranulocytosis following G-CSF therapy.

PMID- 1374637
TI  - Peroral pharyngeal block for placement of esophageal endoprostheses.
AB  - BACKGROUND AND OBJECTIVES: The placement of plastic peroral endoprostheses
      frequently is done in the United States as a palliation for esophageal cancer.
      However, the combination of topical local anesthetics and sedatives, the most
      commonly used means to achieve anesthesia, can cause complications and often does
      not adequately suppress the gag reflex. The purpose of this study was to compare
      sedation requirements in patients receiving the standard topical local anesthetic
      versus patients receiving peroral pharyngeal plexus block. METHODS: From December
      1987 through April 1991, 11 patients underwent endoscopic esophageal stent
      placement. The first six patients received topical 10% lidocaine spray, the other
      five patients received pharyngeal plexus blocks. Supplemental sedation was given
      until the patient closed their eyes but were responsive to verbal stimuli.
      Completeness of block was evaluated by stimulating the posterior oropharynx.
      Total sedative requirements were recorded for each patient. RESULTS: Patients
      receiving pharyngeal plexus block had profound anesthesia and suppression of the
      gag reflex, as determined by examination and the patient's tolerance of the
      procedure. Patients receiving only topical anesthesia and intravenous sedation
      tolerated the procedure poorly and required a greater amount of intravenous
      sedation than those in the blocked group (p less than 0.01). There were no
      anesthetic complications in patients receiving pharyngeal blocks. CONCLUSIONS:
      Our experience indicates that the endoscopic placement of esophageal
      endoprostheses is optimally performed with the aid of pharyngeal plexus block.
      This block provides profound anesthesia with minimal risk in debilitated, high
      risk patients. The neuroanatomy of the oropharynx is also reviewed.

PMID- 1374638
TI  - Human immunodeficiency virus reverse transcriptase: steady-state and pre-steady
      state kinetics of nucleotide incorporation.
AB  - Steady-state and pre-steady-state kinetic constants were determined for reverse
      transcriptase catalyzed incorporation of nucleotides and nucleotide analogues
      into defined-sequence DNA primed-RNA templates. 3'-Azido-3'-deoxythymidine 5'
      triphosphate (AZTTP) was almost as efficient a substrate (kcat/Km) as dTTP for
      the enzyme. In contrast, the four 2',3'-dideoxynucleoside 5'-triphosphates and 3'
      deoxy-2',3'-didehydrothymidine 5'-triphosphate (d4TTP) were 6-30-fold less
      efficient substrates of the enzyme. The kcat values for all nucleotide analogues
      were similar, consistent with a kinetic model in which the steady-state rate
      limiting step was dissociation of the template-primer from the enzyme [Reardon,
      J. E., & Miller, W. H. (1990) J. Biol. Chem. 265, 20302-20307]. The pre-steady
      state kinetics of single-nucleotide incorporation were consistent with the
      kinetic model: [formula: see text] where E, TP, and dNTP represent reverse
      transcriptase, a defined-sequence DNA primed-RNA template, and 2'-deoxynucleoside
      5'-triphosphate (or analogue), respectively. The dissociation constant (Kd1) for
      template-primer binding was 10 nM, and the estimated rate constants for
      association and dissociation of the enzyme.template-primer complex were 4 x 10(6)
      M-1 s-1 and 0.04 s-1, respectively. The dissociation constants (Kd2) for dTTP,
      AZTTP, and 3'-deoxythymidine 5'-triphosphate (ddTTP) were 9, 11, and 4.6 microM,
      respectively. Thus, the differences in steady-state Km values were not due to
      differences in binding of the nucleotide analogues to the enzyme. In contrast,
      the rate-limiting step during single-nucleotide incorporation (kp) was sensitive
      to the structure of the nucleotide substrate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374639
TI  - Distinct alpha-subunit structures of human insulin receptor A and B variants
      determine differences in tyrosine kinase activities.
AB  - Human insulin receptor isoforms (HIR-A and -B) differ in their alpha-subunit
      structures which result from alternatively spliced precursor mRNAs. This
      structural difference causes distinct binding affinities for insulin. To
      determine the impact of the structural difference on receptor signaling, we
      characterized the tyrosine kinase activity of HIR-A and HIR-B in vitro and
      determined the insulin stimulated beta-subunit phosphorylation and tyrosine
      kinase activation in the intact cell. When 32P incorporation in beta-subunits of
      equal amounts of isolated HIR-A and HIR-B was measured, an increased 32P
      incorporation in tyrosine residues of the beta-subunit of HIR-B (2.5-fold)
      compared to that of HIR-A was found after in vitro insulin stimulation. This was
      paralleled by an increased rate of phosphorylation (2.0-fold) or poly(GluNa,Tyr
      4:1). In vitro analysis of Km values for ATP were similar for HIR-A (Km = 14.3
      microM +/- 3.8) and HIR-B (Km = 20.2 microM +/- 8.6), whereas the Vmax of HIR-B
      was significantly increased (HIR-A Vmax = 5.5 mumol/60 min micrograms-1 +/- 1.4,
      HIR-B Vmax = 42.5 mumol/60 min micrograms-1 +/- 19.2). HPLC analysis of tryptic
      beta-subunit phosphopeptides revealed identical patterns, suggesting that the
      difference in kinase activities is not due to an alteration of the
      phosphorylation-activation cascade within the beta-subunit. However, when
      cleavage of the alpha-subunit by short-time trypsinization was used to activate
      the tyrosine kinase, the differences in 32P incorporation between HIR-A and HIR-B
      were abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374640
TI  - Effect of membrane potential on band 3 conformation in the human erythrocyte
      membrane detected by triplet state quenching experiments.
AB  - The triplet lifetime and absorption anisotropy decay of eosin-labeled band 3 was
      measured in resealed erythrocyte ghosts. Membrane potentials were generated by
      the addition of valinomycin in the presence of a K+ gradient. Neither negative
      nor positive membrane potentials had any detectable effect on the rotational
      diffusion of band 3 nor on the eosin triplet lifetime. The membrane potential
      did, however, affect quenching of the eosin triplet state by I- and TEMPO
      (2,2,6,6-tetramethylpiperidine-N-oxyl). Quenching was enhanced by a negative
      membrane potential (negative inside) and reduced by a positive membrane
      potential. In addition, it was found that a negative membrane potential enhanced
      the efficiency of eosin labeling of band 3 in intact erythrocytes. A positive
      membrane potential had the opposite effect. These results indicate that the eosin
      binding site on band 3 becomes more accessible to the extracellular aqueous phase
      in the presence of a negative membrane potential and less accessible in the
      presence of a positive membrane potential. Quenching by I- and TEMPO of the
      triplet state of eosin-labeled band 3 was further investigated as a function of
      pH. Quenching by TEMPO and its dependence on membrane potential were relatively
      insensitive to pH. In contrast, the rate of quenching by I- showed a marked
      decrease over the range pH 5.5-9.5. Moreover, the effect of a negative membrane
      potential on I- quenching also varied with pH. These results are discussed on the
      supposition that the eosin probe is located in the anion access channel of band
      3.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374641
TI  - Comparison of hydrogen exchange rates for bovine pancreatic trypsin inhibitor in
      crystals and in solution.
AB  - Hydrogen exchange rate constants for the 17 slowest exchanging amide NH groups in
      bovine pancreatic trypsin inhibitor (BPTI) were measured in solution and in form
      II and form III crystals. All 17 amide hydrogens are buried and intramolecularly
      hydrogen bonded in the crystal structure, except Lys 41 which is buried and
      hydrogen bonded to a buried water. Large-scale crystallization procedures were
      developed for these experiments, and rate constants for both crystal and solution
      exchange were measured by 1H NMR spectroscopy of exchange-quenched samples in
      solution. Two conditions of pH and temperature, pH 9.8 and 35 degrees C, and pH
      9.4 and 25 degrees C, bring two groups of hydrogens into the experimental time
      window (minutes to weeks). One consists of the 10 slowest exchanging hydrogens,
      all of which are associated with the central beta-sheet of BPTI. The second group
      consists of seven more rapidly exchanging hydrogens, which are distributed
      throughout the molecule, primarily in a loop or turn. In both groups, most
      hydrogens exchange more slowly in crystals, but there is considerable variation
      in the degree to which the exchange is depressed in crystals. Many differences
      observed for the more rapidly exchanging hydrogens can be attributed to local
      surface effects arising from intermolecular contacts in the crystal lattice.
      Within the slower group, however, a very large effect on exchange of Ile 18 and
      Tyr 35 appears to be selectively transmitted through the matrix of the
      molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374642
TI  - Effects of intracellular signals on Na+/K(+)-ATPase pump activity in the frog
      skin epithelium.
AB  - The effects of intracellular signals (pHi, Na+i, Ca2+i, and the electrical
      membrane potential), on Na+ transport mediated by the Na+/K+ pump were
      investigated in the isolated Rana esculenta frog skin. In particular we focussed
      on pHi sensitivity since protons act as an intrinsic regulator of transepithelial
      Na+ transport (JNa) by a simultaneous control of the apical membrane Na+
      conductance (gNa) and the basolateral membrane K+ conductance (gK). pHi changes
      which modify JNa, gNa and gK, do not affect the Na+ transport mediated by the
      pump as shown by kinetic and electrophysiological studies. In addition, no
      changes were observed in the number of 3H-ouabain binding sites in acid-loaded
      epithelia. Our attempts to modify cellular Ca2+ (by using Ca(2+)-free/EGTA Ringer
      solution or A23187 addition) also failed to produce any significant effects in
      the Na+ pump turnover rate or the number of 3H-ouabain binding sites. The Na+
      pump current was found to be sensitive to the basolateral membrane potential,
      saturating for very positive (cell) potentials and a reversal potential of -160
      mV was calculated from I-V relationships of the pump. Changes in Na+i
      considerably affected the Na+ pump rate. A saturating relationship was found
      between pump rate and Nai+ with maximal activation at Nai+ greater than 40
      mmol/l; a high dependence of the pump rate and of the number of 3H-ouabain
      binding sites was observed in the physiological range of Nai+. We conclude that
      protons (in the physiological pH range) which act directly and simultaneously on
      the passive transport pathways (gNa and gK), have no direct effect on the Na+/K+
      pump rate. After an acid load, the inhibition of JNa is primarily due to the
      reduction of gNa. This results in a reduction of Nai and the pump turnover rate
      then becomes dependent on other pathways of Na+ entry such as the basolateral
      membrane Na+/H+ exchanger.

PMID- 1374643
TI  - Monte Carlo studies of a model for lipid-gramicidin A bilayers.
AB  - This paper presents results of Monte Carlo simulations of a full bilayer of 200
      lipid chains and one gramicidin A dimer. Simulations are described for systems
      with lipid chains of 14, 16, and 18 carbons, respectively. Using accepted
      potential functions to calculate interactions between all non-hydrogen atoms a
      Monte Carlo configuration sampling is generated from which order parameter
      profiles are calculated and specific configurations are displayed. Results are
      compared with experimental data for lipid-gramicidin bilayers.

PMID- 1374644
TI  - The stability and functional properties of proteoliposomes mixed with dextran
      derivatives bearing hydrophobic anchor groups.
AB  - Liposomes composed of Escherichia coli phospholipid were coated with
      polysaccharides bearing hydrophobic palmitoyl anchors. The effect on the
      stability of liposomes without or with integral membrane proteins was
      investigated. A high concentration of hydrophobized dextrans protected the
      liposomes against detergent degradation, decreased the fluidity of the membranes,
      prevented fusion of the liposomes and enhanced their stability. Proteoliposomes
      containing beef heart cytochrome-c oxidase and the lactose transport carrier of
      E. coli were similarly affected by coating with the dextrans. Under these
      conditions both membrane proteins were still active. Long-term stability of the
      coated liposomes was obtained only in the absence of the integral membrane
      proteins.

PMID- 1374645
TI  - Properties of plasma membrane-induced amylase release from rat parotid secretory
      granules: effects of Ca2+ and Mg-ATP.
AB  - A secretory granular fraction (SG) and a plasma membrane rich fraction (PM) have
      been isolated from rat parotid gland by differential and Percoll gradient
      centrifugation. With these two fractions, a cell-free interaction system has been
      reconstituted to clarify the exocytotic interaction between the secretory
      granules and plasma membranes, and the conditions of amylase release from SG have
      been characterized in vitro. The addition of PM into this assay system induced a
      rapid and transient release of amylase from SG. Some other membranes such as
      erythrocyte ghosts also mimicked the effect of PM. This release was increased by
      Ca2+, but was not completely blocked by EGTA. Simultaneous addition of 1 mM ATP
      with 1 mM MgCl2 (Mg-ATP) in the presence of Ca2+ reduced this release. However,
      in spite of the existence of Mg-ATP, the stimulation of PM-induced amylase
      release was caused by Ca2+ in a concentration-dependent manner (10(-7)-10(-3) M).
      These results suggest that Ca2+ and Mg-ATP should participate as important
      regulators in the exocytotic interaction between secretory granules and plasma
      membranes in this system. Furthermore, the differences between our system and
      intact cells are also discussed.

PMID- 1374646
TI  - Effects of analogs of the DNA minor groove binder Hoechst 33258 on topoisomerase
      II and I mediated activities.
AB  - By contrast with other DNA minor groove binders, Hoechst 33258 inhibited
      topoisomerase-mediated activity in intact cells. To determine whether specific
      structural alterations could modify the topoisomerase reactivity of this drug, a
      series of analogs of Hoechst 33258 (compound 1) was examined. When the relative
      DNA binding affinities (Ka) of these agents were determined, compound 1 had the
      highest Ka while agents with substitutions in either of the benzimidazole
      moieties showed reduced affinity. Whether these changes in DNA binding correlated
      with topoisomerase inhibitory potency was next examined. In isolated nuclei, 25
      microM of agents 1, 5 and 7 reduced VM-26 induced cross-links by 64, 65 and 83%,
      compared with 15 to 25% reductions by agents 2, 3, 4 and 6, respectively. The
      structural modification common to the less active compounds was the substitution
      of an oxygen for nitrogen at either position 1 or 2. On the basis of these
      results, agents 1, 2, 3 and 7, representing a range of inhibitory potency, were
      chosen for further analyses. Cross-link induction by m-AMSA and camptothecin in
      isolated nuclei, as well as by VM-26 in intact cells, was inhibited to a greater
      extent by agents 1 and 7 than 2 or 3. Additionally, all four drugs inhibited
      relaxation of pBR 322 DNA induced by both topoisomerases, although topoisomerase
      I was 2 to 5-fold more sensitive than topoisomerase II. A linear correlation was
      observed between the logarithms of the Ka value of compounds 1, 2 and 3 and their
      IC25 values for both topoisomerases, suggesting a strong dependence on DNA
      binding affinity for enzyme inhibition. Nevertheless, agent 7, despite having
      less affinity for calf thymus DNA than 1, was the most potent topoisomerase
      inhibitor tested in intact cells and in isolated enzyme systems. Thus, retention
      of nitrogen at positions 1 and 2 as well as the addition of nitrogen at position
      16 was associated with increased topoisomerase inhibitory potency.

PMID- 1374647
TI  - Analysis of a gene cluster coding for the Xenopus laevis U7 snRNA.
AB  - A cluster of Xenopus laevis U7 snRNA genes has been isolated and sequenced. The
      gene structure is more compact than, but otherwise comparable to, the major U
      snRNA genes since the distal sequence element (DSE) is located only 4 nt upstream
      of the PSE. The corresponding RNA is present in the oocyte and accumulates early
      in oogenesis.

PMID- 1374648
TI  - Molecular cloning of substance P receptor cDNA from guinea-pig uterus.
AB  - A cDNA encoding guinea-pig uterine substance P (SP) receptor has been isolated
      using the homology screening approach. Northern blot analysis reveals that the
      corresponding mRNA, of approx. 4.8 kb, is expressed in all tissues tested, but
      predominantly in the uteri of non-pregnant animals; during pregnancy its
      expression is reduced. The guinea-pig SP receptor was expressed in COS-7 cells
      and demonstrated relative ligand affinity in the order: SP much greater than
      neurokinin A greater than neurokinin B.

PMID- 1374649
TI  - Recovery kinetics after chemotherapy and circulating mononuclear cells expressing
      the CD34 antigen in pediatric cancer patients.
AB  - Hematopoietic progenitor cells collected from the peripheral blood are capable of
      restoring hematopoiesis after myeloablative therapy. The numbers of circulating
      mononuclear cells expressing the CD34 antigen were calculated and the colony
      forming capacity was determined in 26 blood samples, which were drawn during
      rapid rise of leukocytes after chemotherapy cycles that were followed by aplasia.
      Culture assay after 14 days revealed a median 507 (210-2029) myeloid progenitors
      (CFU-GEMM/GM) per 10(5) nucleated cells (NC) in 13 CD34-positive samples, and
      only a median 76 (9-224) in 13 CD34-negative ones (p less than 0.001). Median 343
      (175-2450) erythroid burst-forming units (BFU-E) per 10(5) NC were detected in
      the CD34-positive samples, whereas only 72 (10-315) per 10(5) NC were found in
      the negative ones (p less than 0.01). The percentage of CD34-positive cells
      clearly correlated with the growth of CFU-GEMM/GM and BFU-E (p less than 0.01).
      The content of CD34-positive cells in circulation was determined within 120 min
      by FACS analysis and predicted colony-forming capacity of circulating mononuclear
      cells. These observations will help to select the optimal individual days for
      leukaphereses.

PMID- 1374651
TI  - GM-CSF versus G-CSF in the treatment of infectious complication in Felty's
      syndrome--a case report.

PMID- 1374650
TI  - Developmental regulation of granulocyte-macrophage colony-stimulating factor
      production during human monocyte-to-macrophage maturation.
AB  - Cells of the macrophage lineage are a major source of various cytokines and
      hematopoietic growth factors. With regard to the growth factors acting on cells
      of their own lineage, macrophage colony-stimulating factor (M-CSF) has been
      proven to be secreted by monocytes (MO) and macrophages (MAC), whereas the
      production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human
      MO/MAC is under debate. Here we report that in elutriation-purified MO, as well
      as in MAC derived from cultured MO, GM-CSF m-RNA was regularly induced by LPS. In
      MO the GM-CSF message was still detectable 18 h after stimulation under serum
      free conditions, but in contrast was already lost at this time point in MAC.
      Secreted GM-CSF protein was detected in the culture medium using a sandwich
      ELISA. Furthermore, a factor-dependent cell line (M-07) was used for a biological
      assay. Here, a neutralizing anti GM-CSF antibody specifically blocked the
      proliferation-inducing activity of MO/MAC supernatants. Whereas only small
      amounts of GM-CSF were detected in MO, its secretion increased severalfold upon
      MO-to-MAC differentiation in vitro. A similar increase upon in vitro maturation
      of MO was observed for the production of granulocyte colony-stimulating factor.
      The highest amounts of GM-CSF (up to 2.8 ng/10(6) cells) were produced by MAC
      that had been derived from MO cultured under serum-free conditions in the
      presence of 0.5 mg/ml albumin as the only medium supplement.

PMID- 1374652
TI  - CSF 5-HIAA and atmospheric pressure.

PMID- 1374653
TI  - Alkylation of DNA with aziridine produced during the hydrolysis of N,N',N''
      triethylenethiophosphoramide.
AB  - A reaction pathway by which thiotepa (N,N',N''-triethylenethiophosphoramide) and
      tepa (N,N',N''-triethylenethiophosphoramide), its major metabolite in humans,
      alkylate and depurinate DNA involves hydrolysis to aziridine (ethylene imine), a
      highly reactive monofunctional alkylating agent. Hydrolytic cleavage of an N-P
      bond of thiotepa releases aziridine which reacts with DNA, resulting in
      depurination and formation of the stable N-7 adduct 7-(2-aminoethyl)guanine and
      an aminoethyl adduct of adenine. Chromatographically identical alkylated products
      were observed in the reaction of thiotepa and tepa with individual nucleosides.
      Adducts with deoxycytidine or thymidine were not detected. Aziridine was measured
      by HPLC after derivatization with 1,2-naphthoquinone 4-sulfate. On the basis of
      the identity of the DNA adducts and the rate of formation of aziridine by
      hydrolysis in vitro, thiotepa is concluded to be a lipophilic, stabilized form of
      aziridine which serves as a cell-penetrating carrier of aziridine.

PMID- 1374655
TI  - Ultrastructure of alpha 2-macroglobulins.
AB  - New results concerning the ultrastructure of human alpha 2-macroglobulin (alpha
      2M) molecules are presented in connection and comparison with the historical, the
      current and our own most recent, even unpublished results on the structure and
      function of alpha 2M and related proteins. The electron microscopic approach uses
      classical negative staining, combined with the new imaging mode "Electron Energy
      Loss Spectroscopy", which provides unusual contrast, resolution and readability
      of the electron micrographs. Immuno- and cryoelectron microscopy, as well as
      image processing has provided new data necessary to the building of tentative 3D
      models of the molecule. A model for the native tetrameric alpha 2M is described
      for the first time, and tries to explain and gather the various observations,
      sometimes contradictory, taken from different laboratories. A revised version for
      a model of the methylamine- and proteinase-transformed forms of alpha 2M is also
      shown. The probable positions of the bait regions and the thiol esters are given
      on both models. We confirm that alpha 2M is a twin trap capable of inactivating
      one or two proteinases by partial immobilization. Preliminary results on the
      production of crystals of alpha 2M-chymotrypsin complexes are also presented. A
      critical analysis of our models is presented in comparison with others. The
      technical limitations reached with some techniques and some possible extensions
      of future research in the field are also presented.

PMID- 1374654
TI  - Vibrational CD of the amide II band in some model polypeptides and proteins.
AB  - The amide II vibrational CD (VCD) spectra of poly (L-glutamic acid) and poly (L
      lysine) in various conformational forms and those of several proteins in H2O have
      been measured. Characteristic VCD patterns have been observed in the amide II
      region due to helix, beta-sheet, and coil conformations in polypeptides. Based on
      their x-ray crystal structures, the proteins studied have been assigned to six
      categories. Proteins in the same category give rise to similar amide II VCD.
      While the protein conformational type is indicated using the amide II VCD,
      discrimination between types is less characteristic than with the previously
      studied amide I' VCD in D2O.

PMID- 1374656
TI  - Auditory-visual word identification test materials: computer application with
      children.
AB  - The purpose of this investigation was to obtain performance data from normal
      hearing children using the written word portion of existing auditory-visual word
      identification materials, for example, the Picture Identification Task (Wilson
      and Antablin, 1980). The response foils, consisting of four written words (target
      and alternative words) were entered into computer memory so that responses were
      made by pointing to a computer monitor. Subjects were 24 fourth graders with
      normal hearing who repeated auditory-stimulus words in noise in oral conditions,
      and pointed to written words representing the stimulus words in pointing
      conditions. Mean percent correct performance scores were higher in the pointing
      conditions than in the oral conditions, reflecting closed- versus open-set tasks.
      The results indicated that the written word portion of the Picture Identification
      Task can be utilized to assess the word identification performance of children
      who read at a fourth grade level or above.

PMID- 1374657
TI  - Reorganization of the ependyma during axolotl spinal cord regeneration: changes
      in intermediate filament and fibronectin expression.
AB  - Changes in intermediate filament content and extracellular matrix material showed
      that the injury response of ependymal cells in lesioned axolotl spinal cord
      involves an epithelial-to-mesenchymal transformation, and that fibrous astrocytes
      are excluded from the remodeling lesion site. Antibody localization was used to
      visualize cytokeratin-, vimentin-, and glial fibrillary acidic protein- (GFAP-)
      containing intermediate filaments, as well as the adhesive glycoprotein
      fibronectin. In normal axolotl spinal cord cytokeratins were found near the
      apical surface of the ependymal cells. Transmission electron microscopic
      examination suggested that these cytokeratins were in tonofilaments. Cytokeratin
      expression was lost and vimentin production was initiated in ependymal cells 2-3
      weeks following spinal cord injury. There was a period of approximately 1-2 weeks
      when cytokeratins and vimentin were co-expressed in vivo. This co-expression was
      maintained in vitro by culture on a fibronectin-coated substratum. As the central
      canal reformed, vimentin expression was lost. Ependymal cells lacked GFAP
      intermediate filaments, but GFAP was present in fibrous astrocytes of the
      neuropil and white matter. Following injury, GFAP localization showed that
      fibrous astrocytes disappeared from the remodeling lesion site and reappeared
      only after the ependymal epithelium reformed and newly myelinated axons were
      found. Fibronectin expression closely followed the expression of vimentin during
      mesenchymal ependymal cell outgrowth. These results suggest that the ependymal
      cell outgrowth requires changes in cell shape followed by changes in production
      of extracellular matrix.

PMID- 1374658
TI  - The role of hyaluronan-binding protein in assembly of pericellular matrices.
AB  - Hyaluronan-dependent pericellular matrices or "coats" are expressed by a variety
      of cell types in culture and modulation of their expression may be important in
      regulation of cell interactions in vivo during development. Monoclonal antibody
      IVd4, which recognizes hyaluronan-binding protein with the properties of a
      hyaluronan receptor, was shown to block formation of these coats by a variety of
      cells. Using rat fibrosarcoma cells, it was found that the antibody not only
      blocked initial formation of the coats but also caused their loss when added
      subsequent to formation. The loss of preformed coats in the presence of antibody
      occurred at 4 degrees and 37 degrees, implying that the function of hyaluronan
      binding protein in coat formation is not in mediating metabolic processes. The
      antibody also had no significant effect on hyaluronan production by the
      fibrosarcoma cells. In addition, hyaluronan hexasaccharide, a competitive
      inhibitor of the interaction between polymeric hyaluronan and its cell surface
      receptor, was found to inhibit coat formation. Thus it is concluded that a
      hyaluronan-binding protein with the properties of a hyaluronan receptor is
      required for pericellular matrix formation.

PMID- 1374659
TI  - Analysis of chromosomes in molecular tumor and radiation cytogenetics:
      approaches, applications, perspectives.

PMID- 1374661
TI  - The cytometric approach to the study of the cell cycle.

PMID- 1374660
TI  - A new approach to microscopic identification and quantitation of nucleic acids.

PMID- 1374662
TI  - Accumulation of a slow neutron capturing substance,
      mercaptoundecahydrododecaborate (MHB), in cell cultures and biological monitoring
      of the 10B(nth, alpha)7 Li reaction.

PMID- 1374663
TI  - A new approach to the radical histochemistry.

PMID- 1374664
TI  - Comparative study of Langerhans cells in normal and pathological human scars. I.
      Atrophic scars.
AB  - In the present study, we investigated Langerhans cells (LCs) in the epidermal
      component of human atrophic scars, comparing them with those in control skin and
      normotrophic scars. A preliminary analysis of the histological features was first
      carried out on vertical serial sections, stained with hematoxylin and eosin. The
      total epidermal thickness and the thickness of the single epidermal layers were
      then measured, by means of a digitizing tablet and a morphometric program run on
      an Apple IIe computer. These parameters were found to be significantly lower
      (40%) in atrophic scars, if compared to control skin and normotrophic scars (p
      less than 0.05). CDla-positive and HLA-DR-positive LCs were marked by indirect
      immunofluorescence. Their position among the epidermal layers, their dimensions,
      their density and their morphology were examined. In atrophic scars, LCs were
      densely and evenly distributed in all the epidermal layers. Their density was
      increased (about 1200 cells/mm2 of epidermal area), if compared to control skin
      and normotrophic scars (both 300-400 cells/mm2 of epidermal area; p less than
      0.001). The CDla-positive definite cell bodies, exhibiting an unstained nucleus,
      were as large as those evidentiated in the normotrophic scars and twice as much
      the control skin values (p less than 0.001). The present results provide
      morphological data that distinguish atrophic scars from control skin and
      normotrophic scars, and suggest an involvement of the Langerhans cells in this
      particular case of pathological scarring.

PMID- 1374665
TI  - Comparative study of Langerhans cells in normal and pathological human scars. II.
      Hypertrophic scars.
AB  - Langerhans cells (LCs) seem to play a crucial role in the immune system of the
      skin. Changes in their density, distribution, phenotype and/or morphology have
      been described in a number of skin diseases, mostly immunologically mediated. For
      this reason, we investigated LCs in human hypertrophic scars, since these scars
      are presently believed to have an immunological basis. A preliminary analysis of
      the histological features was carried out on vertical serial sections, stained
      with hematoxylin and eosin. Both epidermal and dermal components of hypertrophic
      scar biopsies were examined. The total epidermal thickness and the thickness of
      the single epidermal layers were also measured; the values obtained were similar
      to those of control skin and normotrophic scars. Subsequently, CDla-positive LCs,
      revealed by indirect immunofluorescence and immunoperoxidase techniques, were
      studied to determine their position among the epidermal layers and within the
      dermis, their dimensions, their density and their morphology. According to these
      observations, two main types of hypertrophic scars were identified. In the first
      type (7 scars), LCs were widely clustered within both the whole epidermis and the
      dermis. Their density was increased (about 750 cells/mm2 of epidermal area), if
      compared to control skin and normotrophic scars (both about 400 cells/mm2 of
      epidermal area; p less than 0.001). The epidermal cell profiles, nearly three
      times larger than those of control skin, exhibited a dense network of
      interconnected dendrites. Further analysis for the presence of HLA-DR molecules
      revealed an anomalous expression of these antigens on keratinocytes. In the
      second type (3 scars), LCs density within the stratum Malpighii was unchanged,
      relative to control skin and normal scars, while CDla-positive cell bodies
      remained numerous in basal position and within the subpapillary corion. Epidermal
      LCs, only slightly larger than those evidentiated in control skin, displayed
      short and retracted dendritic projections. The aberrant expression of HLA-DR
      antigens on keratinocytes was very weak and sparse. The present results strongly
      suggest an immunologically activated state of the tissues examined; they provide
      morphological data that support the involvement of the immune system in
      hypertrophic scarring.

PMID- 1374666
TI  - A novel class of nuclear RNA (nRNA) with a long life span as a gene repressor
      candidate.
AB  - Different systemic organs of fetal mice were continuously labelled with 5-3H
      uridine during the organogenesis periods, and chased for various lengths of time
      after birth. In the autoradiographs made on paraffin-embedded sections of the
      organs taken after the chase for longer periods than 1 week, including a 12
      months chase, specific labels were present exclusively in all the nuclei. The
      specific nuclear labels were resistant to RNase A or H digestion and to acid
      hydrolysis with 1 N HCl at 60 degrees C for 5 min, but were completely abolished
      by DNase digestion or prolonged acid hydrolysis for 10 min, the optimum condition
      for the Feulgen reaction to stain DNA. Electrophoretic analysis of the total
      nucleic acids extracted from the different organs chased for 3 or 12 months
      showed all the tritium radioactivity to be present in the DNA fraction before
      digestion with DNase or RNase A, and to be completely absent from the DNA
      fraction and shifted to the RNA fraction, or to be largely destroyed by
      degradation, after each digestion, respectively. By HPLC analysis of the total
      nucleic acid extract after further successive digestions with nuclease P1 and
      alkaline phosphatase into the constituent nucleotides, it was shown that all
      tritium activity was incorporated in uridine, without any detectable label in
      other nucleotides. By the simultaneous labeling of human peripheral lymphocytes
      at the late S-phase with 5-3H-uridine and BrdU, it was demonstrated that the
      autoradiographic labels, which, this time, were labile to RNase A digestion, were
      present in the G-bands of the spread chromosomes as identified by BrdU
      immunohistochemistry. The findings strongly indicate the presence of a novel
      class of nuclear RNA (nRNA). This type of RNA (a) may be localized in the nucleus
      in close association or hybridization with nuclear DNA, (b) have a life span as
      long as that of the cell, and (c) be duplicated in the late phase of DNA
      replication. The nRNA may play a fundamental role as gene repressor existing in
      the G-bands of metaphase chromosomes in the process of ontogeny and
      cytodifferentiation.

PMID- 1374667
TI  - The next step in histochemistry.

PMID- 1374668
TI  - Mallory stain may indicate differential rates of RNA synthesis: I. A seasonal
      cycle in the harderian gland of the green frog (Rana esculenta).
AB  - When Mallory's trichrome stain is used, acinar nuclei of the Harderian gland of
      Rana esculenta display different affinities for the dye. Some of the
      orangiophilic nuclei show affinity for aniline blue (blue nuclei). In the
      Harderian gland of Rana esculenta their number and the intensity of staining with
      aniline blue may vary during the year. The affinity for aniline blue disappears
      following digestion of paraffin sections with RNAase, but not with DNAase or
      trypsin. Furthermore, in vitro incubation with [5, 6-3H]-Uridine shows a
      selective incorporation by the majority of blue nuclei. Therefore, the affinity
      for aniline blue is likely due to increased RNA synthesis. The increment of
      nuclear RNA shown by these methods is supported by the quantitative determination
      of total RNAs during the resumption (October) and enhancement (May) of secretory
      activity, when the percentage of blue nuclei of the acinar cells is at its
      highest levels of the year. The affinity of RNA-rich nuclei for aniline blue,
      while others are strictly orangiophil, is discussed on the basis of molecular
      structure of the dyes used in the staining mixture. Mallory's trichrome stain
      appears to be an useful tool for detecting changes in cell nuclear status.

PMID- 1374669
TI  - Immunocytochemistry: a fundamental tool for a cytochemist.

PMID- 1374670
TI  - Heterochromatin: role of intercalated heterochromatin in gonosome-autosome
      translocations.

PMID- 1374671
TI  - Apoptosis of rat thymocytes triggered by prednisolone, camptothecin, or
      teniposide is selective to G0 cells and is prevented by inhibitors of proteases.
AB  - Rat thymocytes were treated in culture with prednisolone or the DNA topoisomerase
      I or II inhibitors, camptothecin (CAM) or teniposide (TN), and proportions of
      cells in different phases of the cell cycle were estimated by flow cytometry
      using a staining methodology which makes it possible to discriminate between G0
      and G1 cells, as well as to recognize the cells which undergo apoptosis. The
      appearance of apoptotic cells in cultures treated with pharmacological
      concentrations of these drugs, observed as early as 3-6 hr after treatment,
      coincided with the selective loss of G0 cells in these cultures, while no
      significant changes in the proportion of S or G2+M cells were apparent. Agarose
      gel electrophoresis of DNA isolated from the treated cells indicated degradation
      of the internucleosomal spacer sections, typical of the endonucleolytic activity
      which accompanies apoptotic cell death. The data indicate that G0 thymocytes were
      particularly sensitive to agents that induce apoptosis while cells progressing
      through the cell cycle were resistant. This suggests that under in vivo
      conditions (immunological response), the selective death of G0 cells may promote
      the clonal expansion of stimulated thymocytes which enter the cell cycle.
      Together with our earlier studies on the effects of CAM and TN on MOLT-4 and HL
      60 leukemic cell lines, these data indicate that both, phenotypic- and and cell
      cycle phase specific- factors modify the ability of cells to respond to toxic
      agents, including chemotherapeutics by apoptosis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1374672
TI  - HCH, endosulfan, and fluvalinate residue behavior in pigeonpea (Cajanus cajan L.
      Millsp).

PMID- 1374673
TI  - Impact of gamma-BHC on lipid class levels and their modulation by reproductive
      hormones in the freshwater catfish, Heteropneustes fossilis.

PMID- 1374674
TI  - Three discourse profiles of closed-head-injury speakers: theoretical and clinical
      implications.
AB  - This study examined the variation in narrative discourse production noted in an
      earlier report of 11 closed-head-injury (CHI) patients and 21 normal speakers.
      Measures of productivity (fluency), content, and cohesion for two narratives (one
      elicited visually and the other auditorily) were analysed for each CHI speaker.
      Three distinct discourse profiles emerged, categorized as follows: confused,
      impoverished, and inefficient. It is suggested that these data, although
      involving few subjects in each profile, have important theoretical and clinical
      implications. Most particularly, a treatment approach based on each discourse
      profile is presented.

PMID- 1374675
TI  - Communication disorders following closed head injury: new approaches to
      assessment and rehabilitation.
AB  - In this paper communication disorders following closed head injury are described
      and various forms of language assessment techniques are reviewed. The usefulness
      of conventional, pragmatic and cognitive approaches is considered. A new
      cognitive-pragmatic approach is then advocated which is an amalgam of the last
      two approaches. From the examples given it is argued that such an approach is
      practical in terms of: 1) incorporating knowledge of co-existing cognitive
      deficits; and 2) focusing on normal everyday communication practices. It is also
      suggested that the use of a cognitive-pragmatic framework has potential in
      refining remediation and management strategies with the closed-head-injured
      population.

PMID- 1374676
TI  - Genetics of cystic fibrosis.
AB  - The cystic fibrosis gene specifies a membrane transport protein and over 100
      disease-causing mutations have now been identified. Although at least some of
      these determine the incidence of pancreatic disease, there is no association
      between a particular mutation and the severity of lung and liver disease.

PMID- 1374677
TI  - A simple method for insertion of an intraprostatic coil.
AB  - A simplified method of insertion of a urethral coil for treatment of benign
      prostatic obstruction has been tested in 25 patients. The prostatic urethra is
      measured either by abdominal/transrectal ultrasound scanning or by rigid or
      flexible endoscopy. The coil is inserted into the prostatic urethra using simple
      measurements taken from a Foley catheter; 21 coils were correctly positioned at
      the first attempt using this new method--a success rate equivalent to that of
      ultrasound-guided insertion.

PMID- 1374679
TI  - [The relationship between weights of fetuses with autosomal trisomies and low
      maternal serum alpha-fetoprotein].
AB  - An association between low maternal serum alpha-fetoprotein (MSAFP) and fetal
      trisomy has now been thoroughly documented. The mechanisms resulting in low MSAFP
      are still unclear. In order to determine whether the low values of MSAFP in
      autosomal trisomies are associated with smaller fetal weights, we compared 11
      fetuses with Down syndrome (trisomy 21), 4 with trisomy 18, with 45 normal
      fetuses. All of them are aborted in the second trimester of pregnancy. No
      significant difference in the weight distribution between fetuses with Down
      syndrome and control fetuses was found. In contrast, as compared with the control
      fetuses, fetuses with trisomy 18 had a significant lower weight distribution. The
      mean value of MSAFP was 0.72 +/- 0.26 MoM for those with Down syndrome and 0.51
      +/- 0.33 MoM for fetuses with trisomy 18; both results being significantly lower
      than that of normal control (1.01 +/- 0.28). The mean value of amniotic fluid AFP
      was 0.63 +/- 0.23 MoM for fetuses with Down syndrome. This value was
      significantly lower than those of the fetuses with trisomy 18 and normal controls
      (1.02 +/- 0.09 and 1.02 +/- 0.30). A linear relationship between MSAFP and fetal
      weight was found in normal fetuses at a given gestational age but was not found
      in trisomy pregnancy. Fetal weight cannot be used to explain the reason for low
      MSAFP in Down syndrome pregnancy but may partially account for the lower levels
      noted in fetuses with trisomy 18.

PMID- 1374678
TI  - Circulating prostate specific antigen-positive cells correlate with metastatic
      prostate cancer.
AB  - Analytical flow cytometry was used to study circulating prostate specific antigen
      (PSA)-positive cells in 40 consecutive patients with newly diagnosed, untreated
      prostate cancer; 25 patients (63%) had metastatic disease confirmed by a positive
      bone scan. Cell suspensions were prepared for each patient from both the primary
      tumour and peripheral blood samples. The cells were stained with a monoclonal
      antibody against PSA, and analysed by flow cytometry; PSA-positive cells were
      sorted according to their immunofluorescence and light scatter properties. The
      cellular deoxyribonucleic acid (DNA) content of each specimen was also analysed
      to establish ploidy status. PSA-positive cells were detected in the peripheral
      blood of 33 patients (83%). The presence of these cells in the circulation showed
      a higher degree of sensitivity and specificity in predicting positive bone scans
      than did serum PSA levels. Circulating PSA-positive cells may represent either a
      subpopulation of tumour cells with distinct metastatic properties or,
      alternatively, host immunocytes which take up PSA in an active or passive manner.

PMID- 1374680
TI  - Mast cell ionic channels: significance for stimulus-secretion coupling.
AB  - The activation of mast cells (MC) due to immunological stimulation causes an
      immediate and dramatic inflammatory response. We review current evidence
      indicating that the membrane permeabilities for calcium, chloride, sodium, and
      potassium have a significant role in the activation of these cells, and in some
      cases, specific ionic channels have been identified. Moreover, a number of
      intracellular mechanisms controlling these channels are pointed out, including
      different classes of G proteins, intracellular calcium, cAMP, and products of
      phosphoinositol breakdown. However, the interplay between factors controlling
      membrane conductances for different ions is not currently understood. The
      diversity of ionic effects on MC activation is depicted, illustrating that the
      ionic mechanisms of MC activation are specific for different MC types. Since
      nerve/mast cell interaction is a key element in the burgeoning field of
      neuroimmunology, we discuss the role of ionic channels as targets of
      neurotransmitter action in MC activation.

PMID- 1374681
TI  - In vivo circumvention of human colon carcinoma resistance to bleomycin.
AB  - Metabolic inactivation of bleomycin (BLM) by cysteine proteinase-like enzymes is
      thought to be a major mechanism of BLM tumor resistance. We now report that the
      human colon carcinoma COLO-205 is highly resistant to BLM and that E-64, a
      cysteine proteinase inhibitor, sensitizes COLO-205 to BLM. Treatment of COLO-205
      bearing nude mice with either E-64 (40 mg/kg) or BLM (10 mg/kg) alone did not
      inhibit COLO-205 growth. However, pretreatment with E-64 prior to BLM prevented
      these xenografts from growing. Analysis by high performance liquid chromatography
      of in vivo BLM metabolism following [3H]BLM A2 treatment of COLO-205-bearing nude
      mice showed a different metabolic profile among the various organs and the tumor.
      Whereas [3H]BLM A2 was the only major radioactive peak detected in sera and
      tumors, several metabolites, including deamido-BLM A2, were found in kidney,
      liver, and lung as early as 15 min. Pretreatment of mice with E-64 inhibited
      tumor, kidney, and lung BLM A2 metabolism. Furthermore, pretreatment with E-64
      increased BLM A2 accumulation in tumors (6.1-fold), kidney (4.0-fold), lung (2.8
      fold), liver (1.8-fold), and serum (1.7-fold). E-64 pretreatment did not enhance
      the major toxicity of BLM, pulmonary fibrosis, as determined by both lung
      hydroxyproline levels and histopathology. Thus, the cysteine proteinase inhibitor
      E-64 affects the metabolic fate and the levels of accumulation of BLM in vivo.
      These results demonstrate that resistance of human COLO-205 tumors to BLM can be
      circumvented by E-64 without enhancement of the major side effect of BLM,
      suggesting a possible clinical use of this combination therapy.

PMID- 1374682
TI  - A phenotypically and karyotypically stable human thyroid epithelial line
      conditionally immortalized by SV40 large T antigen.
AB  - Primary cultures of normal human neonatal thyroid follicular cells were
      transfected with a plasmid expressing a temperature-sensitive (tsA58) mutant of
      SV40 large T antigen. An epithelial cell line, designated B-thy-ts.1, was
      obtained which showed tight temperature-dependent growth. In sharp contrast to
      previous such lines, which were derived from adult thyroid, B-thy-ts.1 has
      retained a well-differentiated phenotype as reflected in its morphology and
      cytokeratin expression pattern. In addition to phenotypic stability the line also
      displays an unusually stable karyotype, lacking the usual clastogenic effects of
      SV40, which we speculate to result from a greater DNA repair capacity of its cell
      of origin. B-thy-ts.1 should be a particularly useful tool with which to study
      the effects of activated oncogenes on epithelial growth and differentiation.

PMID- 1374683
TI  - Expression of N-myc, c-myc, and MDR-1 proteins in newly established neuroblastoma
      cell lines: a study by immunofluorescence staining and flow cytometry.
AB  - A methodology for rapid isolation of neuroblastoma cells from marrow with
      metastatic neuroblastoma cells was developed using a cocktail of five antibodies
      and magnetic microspheres coated with secondary antibodies. Cells bound to
      microspheres were released by brief exposure to chymopapain, followed by repeated
      culture of released cells in serum-supplemented Dulbecco's modified Eagle's
      medium and selection for adherent cells. Using this methodology, over 35 primary
      cell lines were obtained free of contaminating normal cells. Detailed analyses of
      over 14 cell lines revealed gross differences in cell phenotype, size, morphology
      development of neurite processes, and doubling time (40 to 80 h). All cell lines
      expressed the M(r) 145,000 neurofilament, and a few expressed the M(r) 200,000
      neurofilament, with very little or no expression of the M(r) 68,000
      neurofilament. Eight % of all cells lines had near-diploid DNA content. High
      expression of the MDR-1 protein was detected in six of the 22 cell lines tested.
      Great heterogeneity was observed in the expression of N-myc oncoprotein, with ten
      of 13 patients overexpressing the protein. c-myc oncoprotein was also expressed
      in all cell lines; however, the level of expression was 4- to 10-fold lower than
      the N-myc oncoprotein. Localization studies of c-myc and N-myc oncoproteins on
      the level of light microscopy and electron microscopy revealed exclusive nuclear
      localization of c-myc, whereas N-myc was localized to the nucleus and to the
      cytoplasm.

PMID- 1374684
TI  - Distinct phosphotyrosines on a growth factor receptor bind to specific molecules
      that mediate different signaling pathways.
AB  - The receptor for platelet-derived growth factor (PDGF) binds two proteins
      containing SH2 domains, GTPase activating protein (GAP) and phosphatidylinositol
      3-kinase (PI3-kinase). The sites on the receptor that mediate this interaction
      were identified by using phosphotyrosine-containing peptides representing
      receptor sequences to block specifically binding of either PI3-kinase or GAP.
      These results suggested that PI3-kinase binds two phosphotyrosine residues, each
      located in a 5 aa motif with an essential methionine at the fourth position C
      terminal to the tyrosine. Point mutations at these sites caused a selective
      elimination of PI3-kinase binding and loss of PDGF-stimulated DNA synthesis.
      Mutation of the binding site for GAP prevented the receptor from associating with
      or phosphorylating GAP, but had no effect on PI3-kinase binding and little effect
      on DNA synthesis. Therefore, GAP and PI3-kinase interact with the receptor by
      binding to different phosphotyrosine-containing sequence motifs.

PMID- 1374685
TI  - Influenza virus M2 protein has ion channel activity.
AB  - The influenza virus M2 protein was expressed in Xenopus laevis oocytes and shown
      to have an associated ion channel activity selective for monovalent ions. The
      anti-influenza virus drug amantadine hydrochloride significantly attenuated the
      inward current induced by hyperpolarization of oocyte membranes. Mutations in the
      M2 membrane-spanning domain that confer viral resistance to amantadine produced
      currents that were resistant to the drug. Analysis of the currents of these
      altered M2 proteins suggests that the channel pore is formed by the transmembrane
      domain of the M2 protein. The wild-type M2 channel was found to be regulated by
      pH. The wild-type M2 ion channel activity is proposed to have a pivotal role in
      the biology of influenza virus infection.

PMID- 1374686
TI  - Molecular cloning and nucleic acid binding properties of the GAP-associated
      tyrosine phosphoprotein p62.
AB  - p62 is a tyrosine phosphoprotein that associates with p21ras GTPase-activating
      protein (GAP). Purification and cDNA cloning of p62 reveal extensive sequence
      similarity to a putative hnRNP protein, GRP33. Recombinant human p62 purified
      from insect Sf9 cells binds to DNA and to mRNA and, like many proteins involved
      in mRNA processing, recombinant p62 is modified by dimethylation on multiple
      arginine residues. p62 also binds tightly to p21ras GAP in vitro: this binding
      depends on phosphorylation of p62 on tyrosine residues and occurs through SH2
      regions of GAP. These data suggest that p120-GAP and p62 play a role in some
      aspect of mRNA processing or utilization and that this role may be regulated by
      tyrosine phosphorylation, and indirectly, by p21ras.

PMID- 1374687
TI  - Primary culture of liver cancer tissues with or without transcatheter arterial
      embolization and establishment of a cell strain.
AB  - More epithelial-like cells are found in primary cultures of transcathetel
      arterial embolization (TAE)-untreated human liver cancer tissues than in those of
      TAE-treated tissues. A new cell strain, HUH-33, established from the former,
      grows slowly and is untransplantable into nude mice and secretes alpha
      fetoprotein, albumin and some other tumor markers. Chromosome numbers are widely
      distributed. HUH-33 expresses hepatocyte type keratin and contains desmosome- or
      intermediate filament bundle-like structures.

PMID- 1374688
TI  - Pentafraction reduces the lung lymph response after endotoxin administration in
      the ovine model.
AB  - For the past half-century, several high molecular weight compounds have been used
      for volume expansion during cardiopulmonary resuscitation. However, the
      effectiveness and side effects of these different expanders are varied. We have
      compared plasma, pentastarch, and a new product, pentafraction, for effective
      plasma volume expansion before and after tissue injury with endotoxin
      administration. In each group, eight range ewes instrumented with a Swan-Ganz,
      arterial, and venous catheters, and lung and flank lymphatic cannulas were
      compared. Each group received 15 ml/kg of either 6% pentafraction, 6%
      pentastarch, or plasma followed two hours later by 1.5 micrograms/kg/0.5 hr E.
      Coli endotoxin over 30 min. Data were collected for an additional 24 hr after
      endotoxin administration. Our results indicated a plasma volume expansion in all
      three groups. However, the prior administration of pentafraction significantly
      attenuated the increase in the lung lymph flow and early evaluation of systemic
      vascular resistance noted with endotoxin in comparison to the other two groups.

PMID- 1374689
TI  - Profile of renal permselectivity by simultaneous enzyme-linked immunosorbent
      assay of albumin, transferrin, IgG, and alpha 1-microglobulin with a new
      microplate reader.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) is described for
      determining a renal permselectivity profile involving the urinary proteins
      albumin, transferrin, IgG, and alpha 1-microglobulin (alpha 1-m). The ELISA
      reader uses a computer-controlled array of multiplexed light-emitting diode (LED)
      photodiode pairs for rapid measurements of absorbance on microplates. A 3,3'
      dimethylnaphthidine reagent adapts the 3,5,3',5'-tetramethylbenzidine chromophore
      to monochromatic LED emission at 550 nm. We applied this ELISA to the
      determination of renal permselectivity in healthy children and young adults and
      in children with insulin-dependent diabetes mellitus. The geometric means (and
      SD) of protein excretion rates in a group of 85 normal subjects were as follows:
      albumin, 3.5 micrograms/min (1.83); transferrin, 173 ng/min (2.76); IgG, 1.11
      micrograms/min (2.22), and alpha 1-m, 0.98 microgram/min (2.36).

PMID- 1374690
TI  - Markedly increased alpha-fetoprotein concentration in serum in alcoholic liver
      disease: malignant tumor or nonneoplastic changes?

PMID- 1374691
TI  - Ultrasensitive radioimmunoassay of prostate-specific antigen.
AB  - We describe a modification of the Yang Pros-check radioimmunoassay for prostate
      specific antigen (PSA) that increases the analytical sensitivity of the assay
      approximately threefold (from a working range of 0.3-50 to 0.1-1.2 micrograms/L).
      It can detect PSA added to zero-concentration diluent (bovine serum albumin
      solution) at 0.10 microgram/L or added to zero-concentration control female serum
      at 0.20 microgram/L (P less than 0.05). In 26 patients tested after
      cystoprostatectomy for bladder cancer (who had normal prostates without cancer on
      histologic examination), PSA values by this ultrasensitive assay were all less
      than 0.10 microgram/L. Therefore, we propose this value as the upper limit of the
      95% reference interval. In a retrospective study of two patients who developed
      recurrent prostate cancer, serum PSA values increased above the 0.1 microgram/L
      detection limit 175 and 581 days before increasing above the 0.3 microgram/L
      detection limit of the standard Yang assay. This ultrasensitive radioimmunoassay
      of PSA should prove more useful than current methods for detecting early
      recurrence of prostate cancer.

PMID- 1374692
TI  - Digital rectal examination does not increase serum concentrations of prostatic
      specific antigen.

PMID- 1374693
TI  - Glomerular deposition of complex-forming glycoprotein heterogenous in charge
      (protein HC) in IgA nephropathy.
AB  - IgA immune complexes and polymeric IgA are presumed to play important roles in
      the development and progression of IgA nephropathy. Complex-forming glycoprotein
      heterogenous in charge (protein HC), being inhibitors of neutrophilic chemotaxis,
      has been reported as binding to IgA. As a working hypothesis it was assumed that
      complexes of protein HC and IgA are present in glomeruli from IgA nephropathy
      patient in stable state. In this study, we examined the glomerular deposition of
      protein HC in 40 patients with IgA nephropathy and in 10 patients with non-IgA
      nephropathy. We used highly specific antibody against protein HC, that does not
      cross-react with alpha-1-microglobulin. An immunofluorescent study revealed that
      10 out of the 40 patients (25%) showed an intensity of 1+, 16 (40%) showed weak
      positive (+/-), and the other 14 (35%) were negative. There was no deposition of
      protein HC in non-IgA nephropathy patients. Histopathological analysis
      demonstrated a significant correlation between the intensity of glomerular
      deposited protein HC and pathological activity (p less than 0.005); the latter
      was defined as having either crescents in more than 15% of the remaining
      glomeruli (excluding global sclerotic glomeruli), or segmental necrosis or
      sclerosis in more than 30% of the remaining glomeruli. A significant correlation
      was observed between pathological activity and the intensity of deposited IgG,
      IgA and IgM (p = 0.01), and lambda chain (p less than 0.005). Considering anti
      inflammatory activity of protein HC, these results suggest that protein HC cannot
      protect sufficiently acute inflammation or tissue damages due to co-deposited IgG
      and IgM and/or other factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374694
TI  - The contribution of the peripheral nervous system and the neuropeptide network to
      the development of synovial inflammation.

PMID- 1374695
TI  - Intra-articular injection pentosanpolysulphate results in increased hyaluronan
      molecular weight in joint fluid.
AB  - The influence of an oversulphated glycosaminoglycan, pentosanpolysulphate, on
      hyaluronan metabolism of the synovial lining cell was studied in vivo in human
      volunteers. Significant increases in the mean degree of polymerisation of the
      hyaluronan chains were observed after a series of four to six intra-articular
      injections of this glycosaminoglycan. No increases in hyaluronan synthesis rates
      were observed. Repeated administration of the drug did not cause any inflammation
      or bleeding in the joint cavity.

PMID- 1374696
TI  - Characterization and specificity controls of murine monoclonal antibodies against
      serogroup C1 Salmonella.
AB  - Two IgG3 murine monoclonal antibodies, Cl-1 and Cl-2, that showed serologic
      specificities for the O antigens of serogroup C1 (0:6,7) Salmonella were
      established. The epitopes for the antibodies were found to reside on the
      repeating units of the serogroup C1 Salmonella lipopolysaccharide and were labile
      to sodium metaperiodate oxidation. Serologic reactivities of Cl-1 and Cl-2 were
      not inhibited by commercial monospecific antiserum to O antigen 7, but were
      inhibited to various degrees by anti-[O:6,7] serum. Both antibodies reacted
      strongly with all strains of serogroup C1 Salmonella that have either O:6(1),7,
      O:6(2),7, or O:6(1,2),7 antigens. Reactivities of Cl-1 and Cl-2 with the phage-14
      lysogenized C1 strains that bear the phage-modified O antigen (O:6,7----O:6,7,14)
      were detected by slide agglutination method only and not by whole-cell enzyme
      linked immunosorbent assay. Both Cl-1 and Cl-2 antibodies did not react with
      other O serogroups of salmonellae, nor with other Gram-negative or Gram-positive
      bacteria. The diagnostic value of these monoclonal antibodies together with a
      previously described monoclonal antibody against the serogroup C2 Salmonella was
      demonstrated using the slide agglutination method with monoclonal antibodies
      ascitic fluids.

PMID- 1374697
TI  - Redistribution of natural killer (NK) cell frequency and NK cytotoxic activity in
      primary IgA nephropathy.
AB  - Recent findings have indicated an imbalance of immune responsiveness in primary
      IgA nephropathy (IgAN). Thus natural killer (NK) cell frequency and NK
      cytotoxicity were evaluated in fifteen IgAN patients. CD8+, CD11+, CD56+ and
      CD57+ lymphocyte percentages in IgAN individuals fell within normal values, while
      a significant decrease of CD16+ cells was observed in the same group of patients.
      In contrast, NK activity overlapped that seen in controls as assessed by an
      agarose-single cell cytotoxic assay. To further investigate the discrepancy
      between CD16+ cell level and NK cytotoxic activity in IgAN, the proportion of
      CD11+ CD57+, CD56+ CD16+ and CD57+ CD16+ lymphocytes was determined. In spite of
      the unaffected CD56+ CD16+ cell frequency, IgAN subjects exhibited a significant
      decrease of CD11+ CD57+ and CD57+ CD16+ lymphocyte percentages in comparison to
      controls. It is suggested that a redistribution of NK lymphocyte subsets occurs
      in IgAN. This may have an important role in the impairment of the
      immunoregulatory network.

PMID- 1374698
TI  - Effect of caffeine and isobutyl-methyl-xanthine on production of binucleate cells
      and on post-replicative repair.
AB  - Caffeine (CAF) but not 3-isobutyl 1-methyl-xanthine (IBMX) displayed a strong DNA
      anti-repair effect in G2 prophase, as estimated by the frequency of abnormal
      chromosomes in anaphase-telophase found shortly after treatment. IBMX is more
      effective than CAF in inhibiting cytokinesis, while the binucleate cells formed
      by a short treatment with any of these two xanthines have similar cycle kinetics.

PMID- 1374699
TI  - Effects of verapamil on postextrasystolic potentiation.
AB  - To assess the effects of verapamil on postextrasystolic potentiation (PESP),
      contrast left ventriculography was performed in ten healthy anesthetized dogs
      before and after the intravenous administration of verapamil, 0.1 mg/kg. During
      the contrast ventriculography, a single atrial premature stimulus was introduced.
      Ejection fractions of a control beat and postpremature beat were measured before
      and after verapamil. Before verapamil, the mean ejection fractions of the control
      beat and the postpremature beat were 60 +/- 10 percent and 67 +/- 10 percent,
      respectively (p less than 0.05). Following the administration of verapamil, the
      mean ejection fraction of the control beat decreased from 60 +/- 10 percent to 55
      +/- 11 percent (p less than 0.05). However, the mean ejection fraction of the
      postpremature beats increased when compared with the control beats following
      intravenous verapamil (65 +/- 8 percent and 55 +/- 11 percent, respectively; p
      less than 0.05). These results suggest that PESP is not inhibited by the
      administration of intravenous verapamil.

PMID- 1374700
TI  - A consensus statement on relative merits of EEG and MEG. European Concerted
      Action on Biomagnetism, Lyon meeting, November 26 and 27, 1991.

PMID- 1374701
TI  - Endogenous event-related potentials as indices of dementia in multiple sclerosis
      patients.
AB  - Auditory event-related potentials (ERPs) were recorded in a "double oddball"
      paradigm requiring an easy and a hard pitch discrimination from multiple
      sclerosis (MS) patients with and without dementia, and a group of age and sex
      matched normal subjects. Cognitive function was assessed by a short battery of
      neuropsychologic (NP) tests, and the two groups of MS patients were selected on
      the basis of substantial non-overlapping degrees of cognitive deficit in the
      demented as compared to the non-demented group. The N100, P200 and P300 ERP
      components were longer in latency in the demented patients, and the N100-P300
      interval was prolonged as well, compared to the non-demented patients, whose ERP
      latencies did not differ from those of the normal subjects. Increased P300
      latency was associated with poorer performance on the NP tests, especially those
      sensitive to impairment of learning and retrieval from memory. The reaction times
      of both patient groups were prolonged as compared to the controls, whereas the
      accuracy of the demented patients was significantly poorer than that of the non
      demented patients.

PMID- 1374702
TI  - An event-related potential study of controlled and automatic processes in 6-8
      year-old boys with attention deficit hyperactivity disorder.
AB  - Event-related potentials (ERPs) were recorded from 2 groups (attention deficit
      hyperactivity disorder (ADHD) and normal control) of 12 boys aged from 6 to 8
      years. Subjects were submitted to 2 different types of categorization tasks (with
      rare targets and frequent standards) implying either the use of a verbal class or
      that of an ordered series. Each type of task was performed twice, the first with
      reading and the second without. Amplitudes and latencies of a fronto-central N150
      P250 complex, a parieto-occipital N250-P350 complex and a parieto-occipital P500
      were measured. Regardless of the task, hyperactive children showed larger fronto
      central P250, larger parieto-occipital N250 and smaller parieto-occipital P350s
      and P500s; moreover, the latencies of their parieto-occipital P350s were
      shortened. When the categorization depended on the use of a verbal class, ERP
      reading effects were significantly smaller in hyperactives than in normal
      controls for the parieto-occipital waves only. Alternatively, the target effects
      were significantly larger in hyperactive children but for the fronto-central P250
      only. These results suggest that in ADHD automatic processes were enhanced when
      higher-order controlled processes were inadequate.

PMID- 1374703
TI  - Intermodal selective attention. I. Effects on event-related potentials to
      lateralized auditory and visual stimuli.
AB  - The effects of intermodal selective attention on event-related brain potentials
      (ERPs) were examined in 2 experiments. In experiment 1, auditory ERPs were
      compared (1) when subjects responded to easy and difficult-to-detect target tones
      in sequences of tone bursts; and (2) when they ignored the same auditory
      sequences and played a demanding video game. In experiment 2, auditory ERPs to
      tone bursts and visual ERPs to vertical line gratings were compared as subjects
      responded to difficult-to-detect targets in one modality or the other. Attention
      to auditory stimuli resulted in biphasic enhancements in auditory ERPs, the Nda
      (negative auditory difference wave, latency 120-160 msec) and the Pda (positive
      auditory difference wave, latency 200-240 msec) waves. These had longer latencies
      and somewhat different scalp distributions than N1 and P2 components evoked by
      non-attended tones. The Nda and Pda could be contrasted with the monophasic
      processing negativities typically found in dichotic selective attention tasks.
      Nda amplitudes were larger for difficult-to-detect targets (closely resembling
      standards) than for standards themselves, but no Ndas were recorded to highly
      deviant targets. Deviant auditory stimuli evoked mismatch negativities (MMNs)
      that persisted during visual attention. MMN amplitudes to difficult-to-detect
      deviants were enlarged with attention, but no change was found in MMN amplitudes
      to easy-to-detect deviants. In experiment 2 intermodal attention was associated
      with biphasic changes in visual ERPs over the posterior scalp: the occipital Pdv
      (100-130 msec), and contralateral-temporal Ndv (120-320 msec) deflections.
      Deviant visual stimuli also elicited mismatch negativity/N2b components, largest
      over the inferotemporal cortex contralateral to the stimulated visual field. Like
      the auditory MMN, the MMN increased in amplitude with attention, but it was also
      evident during attend auditory conditions. The results suggest that sustained,
      intermodal attention depends primarily in processing modulations in modality
      specific cortex. We found no evidence of the participation of modality non
      specific cortex. This excludes the possibility that intermodal attention depends
      on a single, supramodal attention system. The relatively long latency of
      intermodal effects suggests that they may depend on the reafferent (top down)
      modulation, and do not index "template matching" operations.

PMID- 1374704
TI  - Intermodal selective attention. II. Effects of attentional load on processing of
      auditory and visual stimuli in central space.
AB  - The effect of processing load on event-related brain potentials (ERPs) was
      investigated in an intermodal selective attention task in which subjects attended
      selectively to auditory or visual stimuli. Processing load was manipulated by
      requiring subjects to detect either difficult-to-detect (deviant) or easy-to
      detect (DEVIANT) targets in separate blocks of trials. Attention to auditory
      stimuli was associated with negative (Nda, 90-170 msec) and positive (Pda, 190
      270 msec) enhancements in the ERPs to auditory stimuli. The Nda increased in
      amplitude with increasing processing load. Deviant auditory stimuli occurring
      among auditory standard stimuli elicited frontally distributed mismatch
      negativities (MMNs). The MMN persisted during visual attention and was unaffected
      by visual processing load. However, the MMN to deviants but not DEVIANTS was
      enhanced in amplitude with auditory attention. Attention to visual stimuli
      resulted in positive (Pdv, latency 70-130 msec) and negative (Ndv, 170-270 msec)
      modulations of visual ERPs, that increased with increasing processing load.
      Prominent visual deviance-related negativities were observed at occipital and
      infero-temporal scalp sites (latencies 90-290 msec), but only to DEVIANT visual
      stimuli. The early MMN-like portion of the visual deviance-related negativity was
      independent of attention, with equal amplitudes during different auditory and
      visual conditions.

PMID- 1374705
TI  - ERP components related to stimulus selection processes.
AB  - Event-related potential (ERP) components associated with target stimulus
      selection in a double discrimination visual task were studied. The experimental
      paradigm consisted in the presentation of low intensity stimuli that varied
      according to two physical features: geometrical form (squares and circles) and
      location (a spot in different positions inside the stimulus). Subjects performed
      3 tasks on these stimuli: control task in which they looked passively at the
      stimuli, and 2 discrimination tasks, in which they had to respond to a certain
      stimulus (a specific conjunction of form and spot location). The early components
      (P1 and N1) obtained in the control and discrimination tasks were associated with
      sensory analysis of simple stimulus features. Relevance of a particular feature
      modified the latency and/or the area of these components. The longer-latency
      components (N2 and P3) were elicited only in the discrimination tasks. N2 was
      associated with target stimulus selection because its area was significantly
      larger for target stimuli and because its "offset" latency correlated with choice
      reaction time. Results are discussed and contrasted with various models of target
      selection.

PMID- 1374706
TI  - Vestibular short latency responses to pulsed linear acceleration in
      unanesthetized animals.
AB  - Linear acceleration transients were used to elicit vestibular compound action
      potentials in non-invasively prepared, unanesthetized animals for the first time
      (chicks, Gallus domesticus, n = 33). Responses were composed of a series of up to
      8 dominant peaks occurring within 8 msec of the stimulus. Response amplitudes for
      1.0 g stimulus ranged from 1 to 10 microV. A late, slow, triphasic, anesthesia
      labile component was identified as a dominant response feature in unanesthetized
      animals. Amplitudes increased and latencies decreased as stimulus intensity was
      increased (MANOVA P less than 0.05). Linear regression slope ranges were:
      amplitudes = 1.0-5.0 microV/g; latencies = -300 to -1100 microseconds/g.
      Thresholds for single polarity stimuli (0.035 +/- 0.022 g, n = 11) were
      significantly lower than those of alternating polarity (0.074 +/- 0.028 g, n =
      18, P less than 0.001). Bilateral labyrinthectomy eliminated responses whereas
      bilateral extirpation of cochleae did not significantly change response
      thresholds. Intense acoustic masking (100/104 dB SL) produced no effect in 2
      animals, but did produce small to moderate effects on response amplitudes in 7
      others. Changes were attributed to effects on vestibular end organs. Results of
      unilateral labyrinth blockade (tetrodotoxin) suggest that P1 and N1
      preferentially reflect ipsilateral eighth nerve compound action potentials
      whereas components beyond approximately 2 msec reflect activity from vestibular
      neurons that depend on both labyrinths. The results demonstrate that short
      latency vestibular compound action potentials can be measured in unanesthetized,
      non-invasively prepared animals.

PMID- 1374707
TI  - Relationship between vertex potentials and magnitude of pre-pain and pain
      sensations evoked by electrical skin stimuli.
AB  - Vertex potentials evoked by painful and non-painful electrical skin stimuli were
      recorded in 10 healthy male volunteers. Peak-to-peak amplitudes of the major
      vertex potential components were compared with subjective rating of the stimuli.
      While a significant correlation was observed between peak-to-peak amplitudes and
      stimulus rating following non-painful stimuli, generally no such correlation was
      present following stimulations above the pain threshold. These findings suggest
      that vertex potentials elicited by electrical skin stimuli may reflect central
      processing of non-noxious afferent information rather than of pain-related
      information.

PMID- 1374708
TI  - A simple format for exchange of digitized polygraphic recordings.
AB  - A simple digital format supporting the technical aspects of exchange and storage
      of polygraphic signals has been specified. Implementation of the format is simple
      and independent of hard- or software environments. It allows for any local
      montages, transducers, prefiltering, sampling frequencies, etc. At present, 7
      laboratories in various countries have used the format for exchanging sleep-wake
      recordings. These exchanges have made it possible to create a common database of
      sleep records, to compare the analysis algorithms local to the various
      laboratories to each other by applying these algorithms to identical signals, and
      to set up a computer-aided interlaboratory evaluation of manual and automatic
      analysis methods.

PMID- 1374710
TI  - A chloroplast gene is required for the light-independent accumulation of
      chlorophyll in Chlamydomonas reinhardtii.
AB  - The light-independent pathway of chlorophyll synthesis which occurs in some lower
      plants and algae is still largely unknown. We have characterized a chloroplast
      mutant, H13, of Chlamydomonas reinhardtii which is unable to synthesize
      chlorophyll in the dark and is also photosystem I deficient. The mutant has a 2.8
      kb deletion as well as other rearrangements of its chloroplast genome. By
      performing particle gun mediated chloroplast transformation of H13 with defined
      wild-type chloroplast DNA fragments, we have identified a new chloroplast gene,
      chlN, coding for a 545 amino acid protein which is involved in the light
      independent accumulation of chlorophyll, probably at the step of reduction of
      protochlorophyllide to chlorophyllide. The chlN gene is also found in the
      chloroplast genomes of liverwort and pine, but is absent from the chloroplast
      genomes of tobacco and rice.

PMID- 1374709
TI  - Nobel lecture. Ion channels for communication between and within cells.

PMID- 1374711
TI  - Identification of the gene(s) coding for the trans-sialidase of Trypanosoma
      cruzi.
AB  - The gene(s) encoding the Trypanosoma cruzi shed-acute-phase-antigen (SAPA) has a
      5' end encoding a region containing two totally and two partially conserved Ser-X
      Asp-X-Gly-X-Thr-Trp motifs which are present in bacterial neuraminidases, and a
      3' end encoding tandemly repeated units of 12 amino acids. It is now reported
      that 54-87% of the total neuraminidase activity present in the parasite could be
      immunoprecipitated with polyclonal or monoclonal antibodies against the repeated
      amino acid units of SAPA. These immunoprecipitates also had greater than 80% of
      the trans-sialidase activity of the parasite. SAPA used sialyllactose, fetuin and
      4-methylumbelliferyl-sialic acid as substrate donors. In the presence of a
      suitable acceptor molecule (lactose) the sialic acid residues were transferred to
      the disaccharide, whereas in the absence of acceptors the residues were
      transferred to water. If relatively inefficient acceptors (maltose or cellobiose)
      were added to the incubation mixtures, the sialic acid units were transferred
      both to the disaccharides and to water. It is concluded that a major T. cruzi
      antigen has both the trans-sialidase and the neuraminidase activities of the
      parasite. Both activities are probably located on the N-terminus of SAPA since
      antibodies directed against the C-terminus, which contains the repeated amino
      acid units, do not affect the enzymatic activities.

PMID- 1374712
TI  - Identification and early activation of a Xenopus laevis p70s6k following
      progesterone-induced meiotic maturation.
AB  - Employing oligonucleotide primers derived from the DNA sequence of rat p70s6k a
      homologous sequence was shown by polymerase chain reaction (PCR) to be present as
      a maternal transcript in stage IV-VI Xenopus laevis oocytes. The sequence covered
      665 bp of p70s6k and was 97% identical at the amino acid level. When used to
      probe a Northern blot of the poly(A)+ mRNA from stage VI oocytes, this sequence
      recognized four transcripts of 1.9, 2.5, 3.2 and 5.2 kb. Specific rat p70s6k
      antibodies immunoprecipitated active S6 kinase from stage VI oocytes but not
      unfertilized eggs. The basal level of activity was 3- to 5-fold higher in primed
      versus non-primed oocytes indicating that p70s6k activation was an early event in
      maturation. Consistent with this observation, progesterone induced a 10-fold
      activation of the kinase in non-primed oocytes within 1 h post-induction at a
      time critical for early activation of protein synthesis. A much smaller, variable
      peak of activation was observed at 85% germinal vesicle breakdown (GVBD), which
      was dependent on the rate of maturation. Two members of the pp90rsk family,
      thought to be the sole S6 kinases present in X.laevis oocytes, exhibited distinct
      kinetics of activation. Finally, the S6 kinase activity present 1 h post
      progesterone stimulation was purified and shown to have a Mr of 70K.

PMID- 1374713
TI  - HOM/HOX homeobox genes are present in hydra (Chlorohydra viridissima) and are
      differentially expressed during regeneration.
AB  - Hydra, a diblastic animal consisting of two cell layers, ectoderm and endoderm,
      is one of the most ancient animals displaying an anteroposterior axis with a head
      and a foot developing from an uncommitted gastric region. As such, hydra is an
      interesting model for studying the presence and function of homeobox genes in a
      phylogenetically old organism. By screening a Chlorohydra viridissima cDNA
      library with a 'guessmer' oligonucleotide, we have cloned several such cnidarian
      homeobox-containing genes (cnox genes). Two of these, cnox1 and cnox2, display
      labial and Deformed type homeodomains respectively and could represent two
      ancestral genes of the HOM/HOX complexes; cnox3 exhibits some similarity to the
      BarH1 and the distal-less type homeodomains and a fourth gene is highly related
      to the msh/Hox7 type of homeodomain. We used quantitative PCR to study levels of
      expression of these genes along the body axis and during head regeneration. In
      all cases, the expression in heads was stronger than that in the gastric region.
      cnox1 transcripts dramatically peaked within the first hours of head
      regeneration, whereas cnox2 and cnox3 reached their maximal levels 1 and 2 days
      after cutting respectively. This differential expression of homeobox genes at
      various stages of regeneration suggests that they play specific roles in
      regenerative processes.

PMID- 1374715
TI  - Effects of heparin on proteolytic activities in human plasma.
AB  - The influence of unfractionated heparin [average molecular weight (MW) 10,000
      15,000 kD] and low-molecular-weight heparin (average MW 400-600 kD) on the plasma
      kallikrein-kinin and the fibrinolytic system was studied in vitro. Unfractionated
      heparin added to plasma gave an increase in kallikrein-like activity with a
      corresponding decrease of prekallikrein and functional kallikrein inhibition
      values. Plasmin-like activity was also increased, but minor changes in
      plasminogen and no change in antiplasmin values occurred. The changes were less
      pronounced with low molecular heparin compared with unfractionated heparin. The
      proteolytic changes were reversed by protamine sulfate but not influenced by the
      protease inhibitor aprotinin. Gel filtration yielded proteolytic activities able
      to split the plasma kallikrein substrate S-2305 and, to a minor degree, the
      plasmin substrate S-2251. The proteolytic activities were not due to complex
      formation with alpha 2-macroglobulin. We speculate that heparin binds to
      prekallikrein to form a heparin-prekallikrein complex which undergoes
      conformational changes and displays a kallikrein-like activity with the ability
      to split small synthetic substrates. Whether it is capable to split natural
      substrates remains unresolved.

PMID- 1374714
TI  - Transcription mapping of a 100 kb locus of Plasmodium falciparum identifies an
      intergenic region in which transcription terminates and reinitiates.
AB  - We have mapped Plasmodium falciparum erythrocytic stage transcription units on
      chromosome 10 in the vicinity of the gene encoding the glycophorin binding
      protein (GBP130) using yeast artificial chromosomes (YACs). Three erythrocytic
      stage transcription units are clustered in a 40 kb region. Two of these genes are
      closely linked, separated by less than 2 kb. Nuclear run-on data demonstrate that
      transcription of these two genes, though unidirectional, is monocistronic. Within
      this intergenic region are the sites at which transcription of the upstream gene
      terminates and the GBP130 gene initiates. These studies represent the first
      description of the minimal and necessary cis-acting elements for transcription
      termination and initiation in this protozoan parasite.

PMID- 1374716
TI  - Cryopreservation of islets of Langerhans does not affect angiogenesis and
      revascularization after free transplantation.
AB  - Cryopreservation of isolated islets of Langerhans will be a necessary procedure
      if pancreatic islet transplantation crosses the threshold for clinical treatment
      of diabetes mellitus. Although successful cryopreservation of rodent, canine,
      porcine and human islets has been documented in the past few years, little is
      known about the influence of the freeze-thaw procedure on the islet's potential
      to induce angiogenesis and revascularization, a process which is of crucial
      importance after free transplantation. We have analyzed the process of
      revascularization of 1- and 10-week-cryopreserved hamster islet isografts using
      intravital fluorescence microscopy. First signs of angiogenesis of cryopreserved
      islet grafts were observed on day 2 after transplantation, characterized by the
      protrusion of capillary sprouts. During the following days these sprouts formed a
      microvascular network, and revascularization was completed on day 10 after
      transplantation. Quantitative analysis of functional capillary density, capillary
      red blood cell velocity, capillary diameter and flow of individual capillaries
      did neither show differences between 1- and 10-week-cryopreserved islets, nor
      differences between cryopreserved islets and islets transplanted without
      cryopreservation were observed. From these results we conclude that
      cryopreservation of isolated pancreatic islet grafts is an adequate technique for
      long-term storage prior to transplantation.

PMID- 1374717
TI  - Baroreceptor reflexes and vascular reactivity during inhibition of nitric oxide
      synthesis in conscious rabbits.
AB  - The effect of the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine (NOLA)
      on vascular reactivity and the baroreceptor heart rate reflex was examined in
      chronically instrumented conscious rabbits. NOLA (15 mg/kg i.v.) significantly
      increased mean arterial pressure and hindlimb vascular resistance and decreased
      heart rate. Increases and decreases in arterial pressure were produced by the
      intravenous injection of phenylephrine and sodium nitroprusside respectively and
      the values obtained relating mean arterial blood pressure to heart rate were
      fitted to a sigmoid curve. NOLA significantly reduced the lower plateau of the
      arterial pressure--heart rate curve but did not significantly affect baroreceptor
      sensitivity. Depressor and hindlimb vasodilator responses to acetylcholine were
      significantly impaired by NOLA whereas responses to sodium nitroprusside were
      significantly enhanced. The pressor and hindlimb vasoconstrictor responses to
      phenylephrine were significantly enhanced in the presence of NOLA. We conclude
      that the bradycardia produced by NOLA does not result from a change in
      baroreceptor sensitivity. The continuous generation of NO appears to be important
      in regulating basal vascular resistance and in modulating vascular reactivity to
      both vasodilator and vasoconstrictor agents.

PMID- 1374718
TI  - Structural requirements for galanin inhibition of pentagastrin-stimulated gastric
      acid secretion in conscious rats.
AB  - The effects of rat galanin, together with a number of its N- and C-terminal
      fragments, on pentagastrin-stimulated gastric acid secretion were studied in
      conscious rats equipped with chronic gastric fistulas. Similarly to its porcine
      counterpart studied previously, at a dose of 3 nmol/kg per h rat galanin was a
      potent inhibitor of gastric acid secretion. The N-terminal fragments, rat galanin
      (1-10) and -(1-15), retained about 60% of the inhibitory potency of the whole
      galanin sequence whilst the C-terminal fragments, rat galanin-(2-29), -(3-29) and
      -(9-29), were unable to produce significant inhibition over comparable dose
      ranges. Surprisingly, however, simply acetylating the alpha-amino group in
      position 9 of rat galanin-(9-29) restored almost full gastric acid inhibitory
      activity in a homologous rat model. We speculate that this could be due to a
      favorable conformational effect on the C-terminal region produced by alpha
      acetylation. These results also suggest that structural features within either
      the N-terminal or C-terminal regions of rat galanin are able to elicit this
      particular biological response. One possible explanation for this could be the
      involvement of more than one rat galanin receptor having different ligand
      recognition requirements.

PMID- 1374719
TI  - Reactivity of human serum antibody with lipopolysaccharide O 78 antigen from
      enterotoxigenic Escherichia coli.
AB  - Fifteen and five of 20 volunteers challenged with the enterotoxigenic Escherichia
      coli strain O 78.H11 showed a fourfold titre increase of serum ELISA antibody to
      the homologous O 78 and the heterologous O 8 lipopolysaccharide antigen,
      respectively. Sixty-three of 191 sera from 1- to 48-month-old German children
      showed serum antibody reactive with O 78 antigen, all but two of these O 78
      positive sera also showed reactivity with at least one further O antigen. Only 14
      of the O 78 reactive sera also showed antibody to heat-labile enterotoxin. In
      addition, soluble O 8 antigen could inhibit the binding of serum antibody to
      absorbed O 78 in 68% of the German children. Antibody reactive with O 78 antigen
      is thus not a reliable serological marker for enterotoxigenic E. coli infection
      in German children.

PMID- 1374720
TI  - Antigenic and genetic analyses of eight influenza C strains isolated in various
      areas of Japan during 1985-9.
AB  - Eight strains of influenza C virus isolated in various areas of Japan between
      January 1985 and January 1989 were compared using monoclonal antibodies to the
      haemagglutinin-esterase (HE) glycoproteins and by oligonucleotide mapping of
      total vRNA. Five of six strains isolated during 1986-9 were closely related to
      one another and also resembled the virus, C/Aichi/1/81, isolated in 1981 in Aichi
      prefecture. This suggests that the C/Aichi/1/81-related viruses had an
      epidemiological advantage over any co-circulating viruses at least during that
      period. One of two 1985 isolates (C/Nara/1/85) was antigenically
      indistinguishable from the C/Mississippi/1/80 strain though their oligonucleotide
      patterns were markedly different from each other. This raises the possibility
      that C/Nara/1/85 may be a recombinant virus which receives its HE gene from the
      C/Mississippi/1/80-related parent.

PMID- 1374721
TI  - Schistosoma mansoni: patch-clamp study of a nonselective cation channel in the
      outer tegumental membrane of females.
AB  - An apparent ion channel with a conductance of 295 pS is present in isolated
      inside-out patches of outer tegumental membrane taken from female Schistosoma
      mansoni. With positive voltages applied to the intracellular face of the patch,
      percentage open time for the channel was 0 to 50; with negative voltages applied,
      percentage open time was greater than 99. Step changes in applied voltage
      characteristically induced opening-closing activity. However, there was no
      maintained applied voltage at which there was a high level of sustained opening
      closing activity. The 295 pS conductance was by far the most commonly occurring
      conductance but it appears to result from cooperativity among several channels,
      the unitary conductance for the channel averaging 95 pS. Alterations in the Na+
      or K+ concentration ratios changed the reversal potential for this conductance
      but alterations in the Cl- concentration did not. From this it is concluded that
      this channel is selective for Na+ or K+ over Cl- and it appears to be a
      nonselective cation channel.

PMID- 1374722
TI  - Pheromone binding proteins of the mouse, Mus musculus.

PMID- 1374723
TI  - Hyperamylasemia associated with lymphadenectomy in patients surgically treated
      for gastric cancer.
AB  - The influence of standard lymphadenectomy on the occurrence of damage to the
      pancreas was evaluated in 28 patients with gastric cancer, by analysing related
      serum and urine enzyme activities, pre- and postoperatively. Enzymatic evidence
      for pancreatic damage was related to the surgical procedure performed.
      Postoperatively, the patients treated by R2 gastrectomy had significantly
      increased levels of P-type amylase in the serum compared with findings in
      patients treated by R1 gastrectomy or bypass procedures. Conversely, the S-type
      amylase in both groups remained within normal limits during the study period.
      Pancreatic secretary trypsin inhibitor (PSTI) and phospholipase A2 (PLA2) proved
      to be less sensitive to pancreas damage caused by lymphadenectomy. The R2
      patients with P-type hyperamylasemia had no major postoperative complications.
      Thus, while the standard R2 gastrectomy may well be a relevant factor associated
      with the occurrence of transient P-type hyperamylasemia, there seems to be no
      relation to major postoperative complications such as pancreatitis.

PMID- 1374724
TI  - Intraperitoneal 5-fluorouracil in the management of colorectal liver cancer.
AB  - Twenty-five patients with colorectal liver metastases had a subcutaneous portal
      connection with a peritoneal catheter implanted for the intraperitoneal (i.p.)
      administration of 5-fluorouracil (5-FU). In five patients, the malignant disease
      rapidly progressed and the implanted catheter system was never used. Among the
      remaining 20 patients, seven patients had i.p. 5-FU as adjuvant treatment
      following liver resection and 13 patients received palliative chemotherapy (5-FU)
      owing to unresectable liver metastases. 5-FU was administered on a regular basis
      every 4 to 6 weeks by continuous infusion of 1000 mg/day (approximately 15
      mg/kg/day) for 5 days. In seven patients, i.p. chemotherapy was managed on an
      outpatient basis. In general, i.p. 5-FU treatment was well tolerated with only
      minor abdominal complaints during the initial treatments. No definite effect on
      survival has been noted. All patients (n = 13) receiving palliative i.p. 5-FU
      died after a median of 4 (range 1.5-18) months. Two patients receiving adjuvant
      chemotherapy died owing to recurrence after 20 and 23 months, while five patients
      are alive, two with recurrent disease and three without, after 14-35 months.

PMID- 1374725
TI  - Carcinoid tumor of the lung: clinicopathological and immunohistochemical studies.
AB  - Carcinoid tumors of the lung in 10 patients were treated surgically and both the
      clinicopathological manifestations and immunohistochemistry were examined in
      detail. Five were central carcinoid tumors, located in the main, lobar or
      segmental bronchus and five were peripheral carcinoid tumors, located in the
      subsegmental bronchus or beyond. Histologically, eight of the tumors were typical
      carcinoid tumors, one was an atypical carcinoid tumor, and one a carcinoid
      tumorlet. Three growth types were also established: polypoid type, iceberg type
      and intrapulmonary type. The central carcinoid tumors belonged either to the
      polypoid type or iceberg type, while the peripheral carcinoid tumors were of the
      intrapulmonary type. Both the iceberg and intrapulmonary types may invade the
      peribronchial or parenchymal tissues more frequently than does the polypoid type.
      Immunohistochemically, argyrophilia and neuron-specific enolase (NSE) were
      detected in all the tumors examined and six stained for polypeptide hormones such
      as adrenocorticotropic hormone (ACTH) and/or pancreatic polypeptide (PP). Of
      these, five had epithelial markers such as keratin, epithelial membrane antigen
      (EMA) and/or carcino-embryonic antigen (CEA). These findings suggest that a
      carcinoid tumor of the lung originates from primitive multipotential stem cells
      such as those of a neuroendocrine or epithelial nature.

PMID- 1374726
TI  - (2'-5')Oligoadenylate and intracellular immunity against retrovirus infection.
AB  - 1. The double-stranded RNA-dependent 2',5'-oligoadenylate (2-5A)
      synthetase/ribonuclease L (RNase L) system plays an essential role in the
      establishment of the antiviral state of a cell exposed to virus infection. 2.
      Until recently, the application of 2-5A derivatives to reinforce this system
      seemed to be limited mainly due to the low specificity of RNase L for viral RNA.
      3. Two new strategies have been developed which yield a selective antiviral
      effect of 2-5As at least against human immunodeficiency virus-1 (HIV-1)
      infection: (i) an "intracellular immunization" approach using 2-5A synthetase
      cDNA linked to HIV trans-acting response element (TAR) and (ii) inhibition of
      retroviral reverse transcriptase activity by 2-5A analogues.

PMID- 1374727
TI  - [Adhesion proteins and the liver. From cell biology to physiopathology].

PMID- 1374728
TI  - Combined endoscopic laser therapy and brachytherapy for palliation of oesophageal
      carcinoma: a pilot study.
AB  - Palliative treatment for oesophageal malignancy aims to maximise symptom relief
      with minimal disturbance to the patient. Twenty one patients with oesophageal
      carcinoma were studied prospectively to assess the combined efficacy of laser and
      brachytherapy in the palliation of oesophageal carcinoma, 20 were unsuitable for
      resectional surgery because of tumour extent and one patient underwent the
      treatment protocol after myocardial infarction, for symptom relief before
      resection. Two patients died at hospital and the remaining 19 survived from 9 to
      455 days (mean 140 days). All patients tolerated the procedure well and
      improvement in swallowing was noted in 19 who survived the procedure--an
      improvement that was maintained until their death. However, five patients
      required oesophageal dilatation after the initial treatment. Results were not
      affected by the histology of the tumour. In summary, combined endoscopic laser
      and brachytherapy is effective palliation for oesophageal carcinoma and may be
      particularly appropriate in those patients with cervical and upper thoracic
      tumours in whom intubation may be unsatisfactory.

PMID- 1374729
TI  - [Prostatic specific antigen for detection and monitoring of prostatic cancer].
AB  - Prostatic specific antigen (PSA) can be detected in normal and benign
      hypertrophic prostates, as well as in prostatic cancer and its metastases. Since
      it appears in the serum, this glycoprotein has become an established marker for
      the detection and monitoring of prostate cancer. Using a radioimmunoassay (CIS-
      Biointernational, France), we found serum PSA levels higher than 4 ng/ml in 55 of
      58 patients with prostatic cancer. The concentrations were proportional to tumor
      stage: significantly higher in stages C and D than in stages A and B (p less than
      0.002). In all 6 cases with occult prostatic carcinoma (stage A), levels were
      higher than 15 ng/ml. PSA was found to be a good indicator of response to
      therapy, as well as a marker of tumor progression during follow-up. After radical
      prostatectomy serum PSA levels decreased to below 1 ng/ml. Following radiotherapy
      levels returned to normal within 1-6 months in 8 of 11 patients. In 21 of 23 with
      metastases serum PSA decreased during hormonal treatment. In 3 who responded
      initially to hormonal therapy, levels increased before clinical manifestation of
      tumor progression. We conclude that PSA is a sensitive serum marker for the
      diagnosis of prostatic cancer in cases of metastatic disease of unknown origin,
      as well as for monitoring the response to treatment of prostatic carcinoma. The
      use of PSA serum levels for screening for prostatic cancer is still
      controversial.

PMID- 1374730
TI  - [Blood coagulation and fibrinolysis in prostate surgery].
AB  - In 23 patients undergoing transurethral resection of the prostate (n = 11) or
      suprapubic prostatectomy (n = 12), hemostasis and fibrinolysis were studied. In
      addition to basic coagulation tests, antithrombin III, plasminogen, antiplasmin
      and fibrin degradation products were determined preoperatively, intra-operatively
      and postoperatively over a period of 6 days. Evaluation of the results revealed
      slightly activated blood coagulation and fibrinolysis intraoperatively and
      postoperatively, with no significant differences being seen between the two
      groups. Routine use of antifibrinolytic drugs in patients undergoing surgery of
      the prostate is not recommended.

PMID- 1374731
TI  - Genetic affinities of oceanic populations based on RFLP and haplotype analysis of
      genetic loci on three chromosomes.
AB  - Restriction fragment length polymorphisms at the renin and factor 13B loci
      located at chromosome 1q32-1q42 were studied in 14 ethnic groups in the west
      Pacific region. The allele frequencies were combined with previously described
      beta-globin and albumin-vitamin D binding protein haplotype frequencies and used
      to assess genetic affinities among eight major ethnic-geographic groups in this
      region. These population groups divide into two clusters with Australian
      Aborigines, Island Melanesians, and Highland Melanesians forming one cluster and
      east Asians, Southeast Asians, Micronesians, and Polynesians forming the other.
      The results indicate that Micronesians and Polynesians are derived from
      populations in Southeast Asia and that they originated independently of the
      Melanesian populations.

PMID- 1374732
TI  - Molecular typing of Neisseria gonorrhoeae by restriction fragment length
      polymorphisms.
AB  - OBJECTIVE: To characterise Neisseria gonorrhoeae isolates by restriction fragment
      length polymorphisms (RFLPs) in ribosomal RNA genes. DESIGN: Generation of RFLP
      patterns by HincII restriction of rRNA genes followed by hybridisation with a non
      radioactive labelled broad spectrum 16 + 23S rRNA gene probe. This typing method
      was developed and compared with MAb based serotyping. SPECIMENS: Forty three
      randomly collected isolates from Bangkok (27 isolates) and Singapore (16
      isolates) were studied. RESULTS: The RFLP patterns generated were reproducible
      and highly discriminatory between strains. Analysis of RFLPs produced by HincII
      restriction of rRNA genes established 9 patterns amongst the 43 isolates
      examined. Strains present within a common serovar could be further subdivided by
      RFLP typing. Identical RFLP patterns were found in some strains that belonged to
      various serovars. CONCLUSION: RFLP typing based on heterogeneities of rRNA gene
      restriction patterns could be advantageously used to complement monoclonal
      antibody based serotyping for further subdivision of serovars. Higher sensitivity
      of this combined approach would enable better differentiation of strains in
      epidemiological studies.

PMID- 1374733
TI  - Pancreatic tumor antigens: diagnostic markers and targets for immunotherapy.

PMID- 1374734
TI  - Spatial localization of distinct rheumatic disease-associated epitopes and the
      RNA "cap" of the U1 snRNP particle.
AB  - The spatial organization of two rheumatic disease-associated epitopes and the RNA
      "cap" structure of the U1 small nuclear ribonucleoprotein (snRNP2) was analyzed
      both in situ and in vitro by two independent interference immuno-assays. Sm and
      RNP autoantibodies, associated with systemic lupus erythematosus and mixed
      connective tissue disease, respectively, were used to probe the epitope
      locations. The Sm epitope on the U1 snRNP structure was localized proximal to the
      RNP. Experiments with an anti-m7G (mRNA "cap") monoclonal antibody revealed that
      an in situ association of the Sm and RNP epitopes with the mRNA "cap" structure
      may exist. Our findings, together with previous observations by others, suggest a
      model for the spatial arrangement of these rheumatic disease-associated protein
      epitopes, and the U1 RNA within the U1 snRNP particle.

PMID- 1374735
TI  - Epitope mapping of the nonspecific cross-reacting antigen using various related
      recombinant proteins expressed in Chinese hamster ovary cells and eight distinct
      monoclonal antibodies.
AB  - Antigenic epitopes of nonspecific cross-reacting antigen (NCA) recognized by 8
      different monoclonal antibodies (MAbs) were analyzed in relation to the domain
      structures of NCA [domains N, I (A1-B1) and M] and CEA [domains N, I (A1-B1), II
      (A2-B2), III (A3-B3) and M]. We reconstructed cDNAs for NCA-N, NCA-N-I-M, CEA-N,
      CEA-N-I, CEA-N-I-II, CEA-N-I-II-III-M in a eukaryotic expression vector, pdKCR
      dhfr, and expressed them in Chinese Hamster Ovary (CHO) cells. The recombinant
      proteins were purified by immunoadsorption and gel filtration. By solid-phase
      enzyme immunoassays, the immunoreactivities of the purified recombinant proteins
      were tested against eight different MAbs reactive with NCA. All 8 MAbs had been
      shown to recognize the protein epitopes of the NCA molecule and classified into
      two groups in terms of the reactivity with NCA and CEA; Group X, 5 clones
      reactive with both NCA and CEA; and Group Y, 3 clones reactive only with NCA. The
      epitopes recognized by two of five Group X MAbs were found to be present on the
      domain N of the NCA molecule as well as of the CEA molecule, and those of the
      three others were on the domain I (A1-B1) of both molecules, respectively. All
      three epitopes of Group Y MAbs, which were unique to NCA, were present on the
      domain I (A1-B1) but not on the domain N of the NCA molecule. The epitope mapping
      reported here helps form the basis for understanding the relation between the
      chemical structure and antigenic activities of the NCA molecule and may be useful
      to study the functions of the NCA molecule, especially those of the respective
      domains.

PMID- 1374736
TI  - Enhanced Ia expression by alveolar macrophages following intratracheal
      administration of bleomycin to rats.
AB  - Bleomycin is an important anticancer drug that causes severe, and sometimes life
      threatening, pulmonary toxicity. Initially, there is an acute inflammation
      followed by an irreversible pulmonary fibrosis. Our studies have focussed on the
      effects of the acute pulmonary inflammation on the state of alveolar macrophage
      activation. To study this, we administered a single dose of 3.6 mg bleomycin/kg
      body weight intratracheally to rats and obtained alveolar macrophages at selected
      times thereafter. Ia expression was determined by fluorescent microscopy of cells
      labelled with a fluorochrome-tagged antibody against rat Ia molecules. We report
      that: 1.) alveolar macrophages have elevated Ia expression shortly after
      receiving intratracheally administered bleomycin; 2.) Ia expression is not
      limited to a specific subpopulation of alveolar macrophages; 3.) Ia expression is
      transient in nature returning to control levels 7-14 days after bleomycin
      administration; and, 4.) the degree of upregulation of Ia expression is directly
      related to the dose of bleomycin administered.

PMID- 1374737
TI  - HCV and HBV infection among multitransfused thalassemics from eastern Sicily.
AB  - Serum specimens from 152 Sicilian multitransfused thalassemic subjects were
      tested for antibodies to hepatitis C virus (anti- HCV) and for HBV markers by
      enzyme linked immunoassay and with reference to anti-HCV, confirmed by
      recombinant immunoblot assay. A high rate (47%) of subjects was anti-HCV
      positive. HBsAg was found in 8% of patients and 55% had anti-HBs or anti-HBc
      antibodies or both. Contrary to HBV infection, anti-HCV seropositivity was
      related to the number of transfused units. The highest anti-HCV prevalence was
      observed between 16 and 20 years; 100% of persons older than 50 years had at
      least one marker of HBV infection. In conclusion, HCV and HBV are widespread
      among multitransfused thalassemic. Probably in our area, particularly during the
      pre-HBsAg screening era, several multitransfused patients were infected by HBV
      more readily than by HCV.

PMID- 1374738
TI  - A naturally occurring opioid peptide from cow's milk, beta-casomorphine-7, is a
      direct histamine releaser in man.
AB  - beta-Casomorphine-7, a naturally occurring product of cow's milk with opiate-like
      activity, was studied for possible direct histamine liberation activities in
      humans. It was found to cause concentration-dependent in vitro histamine release
      from peripheral leukocytes of healthy adult volunteers. Intradermal injection of
      beta-casomorphine-7 induced a wheal and flare reaction in the skin similar to
      histamine or codeine. Oral pretreatment with the H1 antagonist terfenadine
      significantly inhibited the skin responses to beta-casomorphine-7. The
      intradermal injection of an opiate receptor antagonist, naloxone, inhibited in
      vitro histamine release and skin reactions only in a 100-fold excess over beta
      casomorphine-7. These findings suggest that beta-casomorphine-7 can be regarded
      as a noncytotoxic, direct histamine releaser in humans. The clinical relevance of
      these findings deserves further studies.

PMID- 1374739
TI  - Mechanism of nasal secretion mediated via nerve reflex in guinea pigs and
      evaluation of antiallergic drugs.
AB  - In order to confirm the mechanism of nasal secretion mediated via a nerve reflex
      in guinea pigs, the secretory response from the contralateral side was studied
      which was induced by local application of various stimulators. There was no
      difference in the nasal secretion between the contralateral and the stimulated
      sides when the secretion was induced by allergen, histamine, and capsaicin at
      lower doses. Methacholine caused a nasal secretion only on the stimulated side.
      Pretreatment with local anesthetic and ganglionic blockers blocked the secretory
      response bilaterally which was induced by allergen, histamine, and capsaicin.
      Antihistaminics also blocked the secretory response induced by allergen and
      histamine on both sides, but not the capsaicin-induced nasal secretion.
      Unilateral pretreatment with local anticholinergics prevented all secretory
      responses only on the stimulated side. Thus, exogenous and endogenous histamine
      released by the allergen-antibody reaction may stimulate histamine H1 receptors
      located in the sensory nerve endings as trigger, resulting in the secretory
      response mediated via a nerve reflex, while methacholine may act directly on
      nasal glands. Ketotifen and azelastine, which are chemical mediators releasing
      inhibitor with antihistaminergic activity, prevented the nasal secretion induced
      by histamine and allergen. On the other hand, disodium cromoglycate, amlexanox,
      and tranilast had only a slight effect on the allergen-induced nasal secretion.
      The secretory response on the contralateral side induced by various stimulators
      would be useful in the in vivo evaluation of anti-allergic drugs to demonstrate
      the difference in their modes of action.

PMID- 1374740
TI  - Concanavalin A-induced activation of hamster mast cells: morphological changes
      and histamine secretion.
AB  - Peritoneal mast cells of Syrian hamsters release histamine to the action of
      concanavalin A (Con A) in dose-dependent fashion. The rate of release was very
      rapid in the first seconds of cell activation and completed in 60 s after the
      challenge. Morphological changes concomitant to the lectin treatment, followed by
      electron microscopy, show that early signs of exocytosis are seen after 10 s. The
      process starts in peripherally located granules which swell, have a decreased
      density and form pores by fusion of the cellular membrane and the perigranular
      membranes. Then it spreads toward the cell interior by fusion of granules and
      forming intracytoplasmic cavities. Some extruded granules are also observed.
      Preincubation of lectin with rat IgE or with rat serum induced an inhibition of
      its histamine releasing action. Immunization increased the Con A-induced
      histamine release in young but not in older hamsters. An IgE-mediated mechanism
      is suggested for the parallel ultrastructural changes and histamine release
      effects induced by Con A on the hamster mast cell.

PMID- 1374741
TI  - Protective effect of SPR-901 (RBS) on the decrease of peripheral leukocyte number
      in 5-fluorouracil-treated mice.
AB  - 5-Fluorouracil (5-FU) induces a decrease in the number of peripheral leukocytes
      (leukopenia), which is one of the major obstacles in the chemotherapy of cancer.
      The number of peripheral leukocytes decreased by day 4 in mice injected i.p. with
      130 mg/kg of 5-FU and recovered to the normal level by day 8. Such a decrease by
      5-FU was prevented to some extent by the oral administration of 30 mg/kg/day of
      SPR-901. Proliferative responses of bone marrow cells to granulocyte/macrophage
      colony stimulating factor (GM-CSF) or granulocyte colony stimulating factor (G
      CSF) were suppressed by 5-FU treatment and their recoveries were enhanced by SPR
      901. The serum level of IL-6 in 5-FU-treated mice was increased by SPR-901. All
      of the mice treated with 300 mg/kg of 5-FU in combination with SPR-901 survived
      over 15 days, however, only 4 of 10 mice treated only with 300 mg/kg of 5-FU
      survived. These results suggest that SPR-901 acts on macrophages directly or
      indirectly, giving rise to the enhanced production of IL-1, IL-6, and other
      factors. Some of the factors derived from SPR-901 activated macrophages, perhaps
      mainly IL-6, act on the early stage of development of multipotent bone marrow
      progenitors synergistically with GM-CSF.

PMID- 1374742
TI  - Acantholytic squamous cell carcinoma of the uterine cervix with amyloid
      deposition.
AB  - An 84-year-old woman suffered for 1 year from intermittent vaginal bleeding.
      Clinical examination revealed a large ulcerative cervical tumor that was
      histologically classified as well-differentiated squamous cell carcinoma.
      Acantholytic areas, apoptotic cell death, and pronounced amyloid deposition
      characterized the tumor. No evidence of papilloma virus infection was found in
      immunohistochemical examination or in nucleic acid in situ hybridization. Amyloid
      formed globular structures surrounded by neoplastic cells that reacted with
      cytokeratin antibodies. Although the amyloid itself was not labeled, electron
      microscopy showed filamentous degeneration of the squamous cells analogous to
      that described in different types of cutaneous keratin-derived amyloidoses. It
      was concluded that similar pathogenetic mechanisms are involved both in the
      cutaneous amyloidosis and in the amyloid deposition of squamous cell carcinoma.

PMID- 1374743
TI  - The molecular biology of intermediate filament proteins.

PMID- 1374744
TI  - Quantitative color Doppler imaging in untreated and irradiated choroidal
      melanoma.
AB  - Histological data indicate the importance of tumor vascularization as a
      determinant of the biological behavior and the response to radiotherapy in
      choroidal melanoma. Duplex ultrasound and color Doppler imaging, the combination
      of B-mode ultrasound and pulse-waved Doppler analysis, were used to measure
      quantitatively neovascular blood flow in 31 patients with choroidal melanoma.
      Follow-up studies (20 patients) were performed to investigate the change of tumor
      blood flow in choroidal melanomas after radiotherapy. Blood flow was detected in
      30 out of 31 melanomas (size 3.1-17.8 mm) within the tumor and at the tumor base
      with a mean peak systolic frequency of 1.0 kHz (range 0.3-2.7 kHz), a mean end
      diastolic frequency of 0.3 kHz (range 0.1-1.0 kHz), and a mean frequency of 0.7
      kHz (range 0.2-1.3 kHz). Two and six months after 106Ru/106Rh beta-ray
      application, 19 patients showed a significant decrease in peak systolic
      frequency. This occurred with and in advance of the decrease in the tumor size.
      In one patient, a rising maximum systolic frequency after radiotherapy marked a
      recurrent tumor growth. Results indicate that the quantitative measurement of
      tumor blood flow by duplex ultrasound and color Doppler imaging may be a new
      diagnostic modality for monitoring the effectiveness of radiotherapy in choroidal
      melanoma.

PMID- 1374745
TI  - Ultrastructural identification of trigeminal nerve endings in the rat cornea and
      iris.
AB  - Trigeminal nerve terminals in the rat cornea and iris were ultrastructurally
      identified using anterograde tracing with Phaseolus vulgaris-leukoagglutinin (PHA
      L). Electron microscopic immunohistochemistry was used to demonstrate the
      presence and localization of calcitonin gene-related peptide (CGRP) in cornea and
      iris. In the cornea and iris, nerve fibers were labelled with PHA-L throughout
      the stroma. Labelling was most obvious within varicosities, densely packed with
      mainly clear and a few granular vesicles and containing dark mitochondria.
      Numerous fibers in the stroma of cornea and iris were CGRP-positive. CGRP
      positive staining was most intense within varicosities, containing mainly clear
      and incidentally granular vesicles and dark mitochondria, similar to the
      structures labelled with PHA-L. CGRP-positive varicosities packed with mainly
      clear and few granular vesicles also were demonstrated in fibers adjacent to the
      sphincter and dilator muscles of the iris. In the corneal epithelium, small
      terminals containing vesicles were CGRP-positive. Trigeminal nerve fibers
      innervating the rat cornea and iris contained numerous varicosities packed with
      vesicles. These areas are CGRP-positive, so it can be implied that CGRP is
      released from these varicosities as a response to triggering impulses. This
      agrees with the hypothesis that in addition to their afferent function, sensory
      fibers also exert an efferent modulating function.

PMID- 1374746
TI  - Identification of a major continuous epitope of human alpha crystallin.
AB  - Human lens proteins were digested with trypsin or V8 protease, and the resulting
      peptides resolved on a C18 reverse phase column. Fractions from this column were
      probed with polyclonal antiserum made against the whole alpha crystallin
      molecule. Peptides in the seropositive fraction were purified to homogeneity,
      then characterized by mass spectral analysis and partial Edman degradation. The
      tryptic and V8 digests contained only one seropositive peptide that was derived
      from the C-terminal region of the alpha-A molecule. To determine the exact
      boundaries of the epitope, various size analogues of this region were synthesized
      and probed with anti-alpha serum. Together, these studies demonstrate that the
      major continuous epitope of the alpha-A chain includes the sequence KPTSAPS,
      corresponding to residues 166-172 of the human alpha-A crystallin chain.

PMID- 1374747
TI  - [Complex progressive palliation for univentricular circulation].
AB  - The type of palliative procedures (PP) for complex univentricular circulation
      (UC) changed significantly during the 80ies. Between 07/86 and 02/91 77 patients
      (pts) presented with UC to eventually undergo a modified Fontan-Kreutzer-type
      operation (MFKTO). 33 pts had been previously palliated, 22 of whom were accepted
      for MFKTO as well as an additional 9 not palliated pts (group A: 31 pts; 20 PP).
      11 previously palliated pts and 35 new pts required new palliations (group B: 46
      pts; 89 PP), 34 of which resulted in 13 MFKTO. Prerequisites to be met for MFKTO
      are: undistorted PA-anatomy; absence of subaortic stenosis (SAS); Qp greater than
      2.5 l/min/m2; PAP less than 20 mm Hg; Rp less than 3 Wood Units. All earlier PP
      in group A (31 BTS, 3 PAB, 2 PA-valvotomy/dil.) merely prolonged survival by only
      adjusting Qp. In group B PP comprise reconstruction of pulmonary arteries, aortic
      arch and isthmus as well as bypass or resection of SAS or atrial septectomy.
      Mortality for complex PP (group B) was 32.5% (15/46). 9 of these pts were
      neonates, 7 after modified Norwood procedures. In an attempt to plan a MFKTO for
      all pts presenting with UC (group B), complex PP was necessary. The high
      mortality is due to lesions in pts who would not have survived if only closed PP
      were applied.

PMID- 1374748
TI  - Quantification of the cellular proliferation on freshly dispersed cells from rat
      anterior pituitaries after in vivo and in vitro labelling with bromodeoxyuridine.
AB  - The labelling index i.e., the proportion of cells in S phase of the cell cycle,
      has been calculated in cytospin preparations of rat anterior pituitary cells
      after labelling either in vivo or in vitro with the thymidine analogue
      bromodeoxyuridine (BrdU). The aims of this work were (1) to check whether
      enzymatic digestion interferes with the incorporation of BrdU into S phase cells
      and/or whether it has any deletereous effect on the immunohistochemical detection
      of cells that have already incorporated BrdU, and (2) to check the viability of
      simultaneous staining for BrdU and markers for the different types of pituitary
      cells in the cytospins. No statistical difference was found between the labelling
      index after in vivo or in vitro labelling with BrdU. Identification of doubly
      immunostained cells was straightforward and up to 40% of BrdU-labelled cells were
      immunopositive for pituitary hormones. It is suggested that cytospin preparations
      from biopsy samples may be used to study cellular proliferation without exposing
      the patient to the hazardous effects of BrdU infusion and without the
      interference of cell culture methods.

PMID- 1374750
TI  - Responsiveness to adipogenic agents in stromal-vascular cultures derived from
      lean and preobese pig fetuses: an ontogeny study.
AB  - Primary cultures of stromal-vascular (S-V) cells from adipose tissue were used to
      evaluate characteristics of preadipocytes from lean and preobese fetuses at
      several ages (50, 75, and 110 d). In insulin-supplemented (1 microM) cultures
      (serum free) there was a significant age x fetal genotype interaction (P less
      than .01) for glycerol-phosphate dehydrogenase specific activity (GPDH); GPDH
      activity was genotype-dependent at 110 d (preobese greater than lean). The
      responses of S-V cultures (preadipocyte development) to 2% pig serum and to
      insulin (serum free) were similar. Main effects of genotype and age were
      significant (P less than .05) for protein levels in pig serum and insulin-treated
      cultures. There was a significant genotype x age (P less than .05) interaction
      for GPDH activity and protein levels in cultures treated with dexamethasone + 3
      isobutyl-1-methylxanthine (DEX-IBMX). Treatment with DEX-IBMX induced more
      preadipocyte development in cultures from preobese fetuses than in cultures from
      lean fetuses at 110 d (P less than .05). The responsiveness of S-V cultures to
      DEX-IBMX (enhanced development) increased considerably between 50 and 75 d
      regardless of fetal genotype, but there was little response in cultures form 50-d
      fetuses. Preadipocyte development in lean and preobese fetuses diverged between
      75 and 110 d, resulting in many more preadipocytes in preobese fetuses at 110 d.
      Therefore, S-V cells from preobese fetuses (late term) may be inherently more
      sensitive to adipogenic agents than S-V cells from lean fetuses.

PMID- 1374749
TI  - Cytokeratin expression in oral exfoliative cytology: effect of temperature and
      fixation.
AB  - The identification of keratin expression within oral cytology may be useful in
      the diagnosis of clinically suspicious oral mucosal lesions. There may be wide
      variation in the temperature at which such smears are stored, prior to
      processing. Conventionally, rapid fixation or storage at low temperatures is
      recommended to preserve kertin expression within tissue biopsies. No previous
      study has assessed whether this is true for oral cytology. Smears were taken from
      clinically normal buccal mucosa. For each temperature assessed (-70, -40, -22,
      +5, +20 and +26 degrees C), one smear was spray-fixed (Vale Smear Fix) and one
      air-dried, prior to storage for 4 days, and then staining with the pan-epithelial
      antikeratin antibody, LP34. Preservation of keratin expression was assessed as
      either weak (zero to few positive cells) or strong (most cells positive). The
      results were analysed using logistic regression with the statistical modelling
      package, GLIM. Over the range of temperatures studied, spray fixation did not
      appear to improve the identification of keratin expression. Although the best
      preservation was obtained at lower temperatures, keratin expression was still
      adequate after 4 days at 20 degrees C. Hence, a delay in processing of 4 days
      would still allow detectable expression in oral exfoliative cytology even at room
      temperature.

PMID- 1374751
TI  - Cimaterol reduces beta-adrenergic receptor density in rat skeletal muscles.
AB  - Interactions between the beta-adrenoceptor agonist cimaterol and beta
      adrenoceptors on rat skeletal muscle membranes were examined in two studies. In
      Exp. 1, muscle samples from eight Sprague-Dawley rats (female, approximately 200
      g) were used for competition binding and autoradiographic studies using
      [125I]cyanopindolol (ICYP) as a radioligand. The affinities or dissociation
      constants for binding (KD values) for cimaterol in plantaris and soleus muscles
      were .68 and .92 microM, respectively. Muscle areas stained for succinic
      dehydrogenase had propranolol-resistant ICYP binding sites; cimaterol did not
      seem to compete for these sites. In Exp. 2, 60 Sprague-Dawley rats (female,
      approximately 218 g) were fed 0 or 10 ppm of cimaterol in rat diet that was
      ground. Groups were killed after 1, 3, 7, 14, or 28 d of treatment. Cimaterol
      increased BW gain up to 14 d after commencement of treatment, with little or no
      improvement thereafter. Enhanced weight gain in skeletal muscles also occurred up
      to 14 d of cimaterol treatment. Densities of beta-adrenoceptors in plantaris and
      soleus muscle membrane homogenates were estimated using a radioligand binding
      assay with ICYP. A significant reduction in the number of binding sites (Bmax)
      was observed after 3 d of cimaterol treatment in plantaris muscle without a
      change in the KD of ICYP binding. The percentage reductions in Bmax were 26.8,
      42.2, 37.7, and 37.8% at 3, 7, 14, and 28 d after cimaterol administration,
      respectively. In the soleus muscle, significant reductions (44.1 and 29.8%) in
      Bmax were observed after 3 and 14 d of cimaterol treatment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1374752
TI  - Production of heparin-binding angiogenic factor(s) by bovine corpora lutea during
      pregnancy.
AB  - Effects of luteal-conditioned media (LCM) on proliferation and migration of
      endothelial cells were used to assess angiogenic activity of corpora lutea (CL)
      obtained from cows on d 100 (n = 5), 150 (n = 6), 200 (n = 6), and 250 (n = 6) of
      gestation. Explants of CL (200 mg) were incubated for 6 h in 3 mL of serum-free
      media containing no hormone, LH (1 microgram/mL), prostaglandin F2 alpha (PGF2
      alpha; 3 microM), or both hormones. Media from the four stages of gestation were
      subjected to the following procedures: 1) ultrafiltration, 2) high-salt (3.0 M
      NaCl) treatment and then ultrafiltration, 3) heat treatment, 4) heparin-Sepharose
      affinity chromatography, 5) immunoneutralization with specific antibodies against
      heparin-binding growth factor (HBGF)-1 and against HBGF-2, and 6) dot immunoblot
      assay for HBGF-2. Fractions from the first five procedures were evaluated in the
      endothelial cell proliferation bioassay. In addition, progesterone concentration
      of LCM was determined by RIA. Across all days of gestation and hormone
      treatments, LCM stimulated (P less than .05) proliferation and migration of
      endothelial cells, but activities did not differ among stages of gestation or
      hormone treatments. Both mitogenic and migration-stimulating fractions seemed to
      have Mr greater than 100,000. The mitogenic activity fraction had an apparent Mr
      greater than 100,000 even after treatment with high salt and was heat-labile.
      This endothelial mitogen was retained on heparin-Sepharose columns and was eluted
      with 2.0 M NaCl. Mitogenic activity was partly neutralized (P less than .05) by
      antibodies against HBGF-2 but not HBGF-1. Presence of HBGF-2 in LCM was detected
      by dot immunoblot assay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374753
TI  - Use of DNA probes to monitor nutritional effects on ruminal prokaryotes and
      Fibrobacter succinogenes S85.
AB  - We used DNA probes to study dietary effects on the prokaryotic population in the
      rumen. Procedures used to isolate and quantify prokaryotic 16S ribosomal RNA
      (rRNA) from the rumen using universal and species-specific DNA probes were
      evaluated. In this experiment, three ruminally fistulated steers were fed orchard
      grass hay, and ruminal digesta were collected at 0, 3, and 9 h after offering hay
      (0800). Samples of ruminal digesta were taken from the interior portion of the
      digesta mat and from the fluid below the mat in the dorsal rumen. Freezing (-65
      degrees C) and blending samples both increased (P less than .07) the yield of 16S
      rRNA from ruminal digesta. Extraction of prokaryotic rRNA was greater (P less
      than .04) when phenol buffered with sodium acetate was used than when it was
      buffered with hydroxymethyl-amino-methane. Prokaryotic 16S rRNA concentration of
      the fluid phase was similar (P greater than .10) at 0, 3, and 9 h after offering
      hay. Prokaryotic 16S rRNA concentration of the mat phase increased up to the 9 h
      after feeding. The proportion of Fibrobacter succinogenes remained constant in
      both digesta phases at all times measured. From these data we concluded that DNA
      probes can be used to monitor bacterial population shifts in the rumen.

PMID- 1374754
TI  - Level of nutrition and visceral organ protein synthetic capacity and nucleic acid
      content in sheep.
AB  - Thirty-two crossbred wether lambs were assigned to a feed intake level of either
      ad libitum (ADLIB) for maximum rate of growth or restricted to maintain body
      weight (MAINT) throughout a 21-d period. At 7-d intervals (d 0.7, 14, and 21),
      four lambs per treatment were slaughtered to obtain measurements of visceral
      organ protein synthetic capacity and tissue composition. Protein synthetic
      capacity was assessed by in vitro [14C]valine incorporation and tissue RNA, DNA,
      and protein contents. Concentrations of protein and RNA were not significantly
      affected in most tissues measured. However, for liver, duodenal, and jejunal
      tissue, DNA concentrations in ADLIB lambs were lower (P less than .05) than in
      MAINT lambs. Ratios of protein:DNA in most organs were higher (P less than .05)
      in ADLIB than in MAINT lambs. During the 21-d period, liver and small intestinal
      protein and RNA mass were higher (P less than .10) in ADLIB than in MAINT lambs,
      and DNA mass was unaffected. Also during the 21-d period, the average total mass
      of ruminal protein, RNA, and DNA in ADLIB lambs was higher (P less than .05) than
      in MAINT lambs. Estimates of valine incorporation and ratios of RNA:protein
      seemed to reflect protein synthetic capacity of the visceral tissues measured;
      however, the effect of level of feed intake on these measurements was equivocal.
      These data suggest that the level of feed intake affected visceral organ mass
      through changes in cellular hypertrophy.

PMID- 1374755
TI  - Three cell lines showing androgen-dependent, -independent, and -suppressed
      phenotypes, established from a single tumor of androgen-dependent Shionogi
      carcinoma 115.
AB  - We investigated the heterogeneity of cells in terms of androgen responsiveness
      within a single tumor mass of Shionogi carcinoma SC-115 showing androgen
      dependent growth. After cloning of the tumor by the limiting dilution method in
      the presence of androgen, we isolated 40 clones at random. Twenty-two clones
      required androgen for growth (androgen-dependent phenotype), 16 did not (androgen
      independent phenotype), and the remaining two clones showed growth inhibition
      when androgen was added (androgen-suppressed phenotype). In addition, 22 androgen
      dependent clones showed heterogeneity in growth factor sensitivity in the absence
      of androgen. All clones were sensitive to both acidic and basic fibroblast growth
      factor (FGF), 7 of 22 clones were sensitive to epidermal growth factor (EGF) and
      transforming growth factor (TGF)-alpha, and 2 of 22 clones were sensitive to TGF
      beta. This preexisting heterogeneity may be partly responsible for the growth of
      androgen-dependent tumor under hormone-deprived circumstances. Three typical
      clones, SC2G, SC1G, and SC4A, were selected from androgen-dependent, 
      independent, and -suppressed phenotypic groups, respectively. These clones, as
      well as original solid tumors, were found to produce heparin-binding growth
      factors of heterogeneous elution positions. The molecular nature of these growth
      factors is not yet known. Neither anti-basic FGF antibody nor anti-EGF antibody
      inhibited the cell growth when added in cell culture, suggesting the factors were
      distinct from basic-FGF and EGF.

PMID- 1374756
TI  - Morphological heterogeneity and phenotypical instability versus metastatic
      stability in the murine tumor model ER 15-P.
AB  - At clinical presentation, the majority of malignant tumors are composed of
      multiple clonal subpopulations of tumor cells with different phenotypic
      characteristics. Using the experimental tumor model ER 15-P, a methylcholanthrene
      induced pleomorphic sarcoma of the C57 Bl6J mouse, we studied a system of long
      term in vivo passages of this primary tumor for cell morphological changes, and
      alterations in the potential for spontaneous lung metastases. Transplants from
      the primary after the 4th, 20th, 40th and 80th i.m. passage (referred to as T4,
      T20, T40, and T80 respectively) together with their lung metastases were
      investigated by light microscopy, immunohistochemistry, and electron microscopy.
      In addition, the potential for metastasis to the lungs in each group was
      determined and compared with that of the parent T4 tumors. T4 tumors were mainly
      composed of spindle-shaped tumor cells with the ultrastructural features of
      fibroblasts and myofibroblasts, often arranged in a storiform or fasciculated
      growth pattern, and intermingled with tumor giant cells. Some small areas
      contained polygonal or rounded tumor cells, ultrastructurally undifferentiated,
      and sometimes arranged in a hemangiopericytoma-like growth pattern. Although
      electron-microscopical findings clearly demonstrated the mesenchymal origin of
      these tumor cells, immunostaining with a polyclonal antibody to vimentin was
      unspecific in all tumor cells and normal mouse tissue. Monoclonal antibodies to
      vimentin from different sources were completely negative in tumor cells and
      murine stromal components. In contrast, myofibroblast-like tumor cells showed
      immunohistochemically, a moderate to strong co-expression with monoclonal
      antibodies to desmin, muscle actin and alpha-smooth muscle actin. On the basis of
      these morphological findings, the primary ER 15-P was classified as a pleomorphic
      myofibrosarcoma. The lung metastases of T4 tumors were mainly composed of
      undifferentiated round to polygonal tumor cells, while the number of desmin
      positive, muscle- and alpha-smooth muscle-actin-positive cells was reduced. The
      morphological features of T20 tumors and their lung metastases were the same as
      in T4, indicating a relative stability of the phenotype up to that stage. In
      contrast, T40 and T80 tumors and their lung metastases were found to contain
      almost exclusively undifferentiated tumor cells and many tumor giant cells. While
      fibroblast-like tumor cells were seen only occasionally, myofibroblast-like tumor
      cells had almost completely disappeared. The potential for lung metastases was
      nearly constant in all groups, suggesting metastatic stability. Obviously, the
      undifferentiated tumor cells of this model are associated with a higher
      metastatic potential.

PMID- 1374757
TI  - CD7-positive acute myeloid leukemia: further evidence of cellular immaturity.
AB  - Among 63 cases of acute myeloid leukemia (AML), 14 were found to express the CD7
      antigen, a cell surface marker usually found at an early stage during T lineage
      differentiation. The CD7-positive AML cases consisted of 5 cases of M1, 3 cases
      of M2, 3 cases of M4, 1 case of M5, 1 case of M6 and 1 case of M7. Among these 63
      cases, the proportion of blast cells expressing the CD34 antigen was examined.
      The proportion of CD34-stained cells among the CD7-positive AML cases, although
      varying, was significantly larger than that among the CD7-negative AML cases (P
      less than 0.05). As the CD34 antigen was expressed on hematopoietic progenitor
      cells and was considered to reflect an early hematopoietic stage, the high
      proportion of cells expressing CD34 among the CD7-positive AML cases may support
      the notion that CD7-positive AML cells are immature.

PMID- 1374759
TI  - Labored breathing in an elderly woman with hypertension.

PMID- 1374758
TI  - The endocytic hyaluronan receptor in rat liver sinusoidal endothelial cells is
      Ca(+2)-independent and distinct from a Ca(+2)-dependent hyaluronan binding
      activity.
AB  - Isolated and cultured rat liver sinusoidal endothelial cells (LECs) retain the
      ability to specifically bind 125I-hyaluronan (HA) and internalize it using a
      coated pit pathway [Biochem J, 257:875-884, 1989]. Here we have determined the
      effect of Ca+2 on the binding and endocytosis of HA by LECs. 125I-HA binding to
      intact LECs at 4 degrees C occurred both in the absence (10 mM EGTA) or the
      presence of physiologic concentrations of Ca+2 (1.8 mM). However, the specific
      binding of 125I-HA to LECs increased linearly with increasing Ca+2
      concentrations. After permeabilization with the nonionic detergent digitonin, the
      Ca(+2)-independent HA binding activity increased approximately 743%, while the
      Ca(+2)-dependent binding activity was enhanced only approximately 46%. Therefore,
      the Ca(+2)-dependent HA binding activity appears not to be intracellular, whereas
      the Ca(+2)-independent HA receptor is found both inside LECs and on the cell
      surface. When LECs were allowed to endocytose 125I-HA at 37 degrees C in 10 mM
      EGTA or in 1.8 mM Ca+2, no differences were seen in the extent or rate of
      endocytosis. When LECs were allowed to endocytose 125I-HA in the presence of 10
      mM Ca+2, the amount of cell-associated radioactivity increased approximately 20
      50-fold. However, this additional cell-associated 125I-HA was not sensitive to
      hyperosmolarity and was removed by washing the cells in 10 mM EGTA at 4 degrees
      C. Therefore, the Ca(+2)-dependent cell-associated 125I-HA had accumulated on the
      cell surface and had not been internalized. From these studies we conclude that
      LECs have at least two types of specific HA binding sites.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1374760
TI  - Separation techniques for biotechnology in the 1990s.
AB  - Scientists are constantly looking for better and cheaper separation techniques to
      replace or complement the current technology. Over the past few decades, and in
      particular the last 10 years, new separation techniques or modifications of
      existing techniques have become available for separating compounds from complex
      sample matrices. There are many areas, however, where the separation technology
      is not sufficient to achieve high purity and yield while remaining cost
      effective. In the area of biotechnology, separation techniques are urgently
      needed to meet demands for ultra-high purity and yield. Thus, a variety of
      techniques are being developed to address these needs. Generally, biological
      compounds for the pharmaceutical and biotechnology industries must be obtained at
      greater than 99.9% purity (sometimes greater than 99.99%) while maintaining high
      yield. In any area of chemistry this degree of purity would cause problems; in
      biotechnology it is even more difficult to achieve because of the complex sample
      matrices. In addition, the compounds of interest may be very similar to
      impurities or contaminants in the sample matrix, and the compounds could be
      denatured (or even destroyed) by certain solvents and/or high temperature. In
      particular, three areas of biotechnology have presented scientists with problems
      in separations: cell separations, DNA-RNA separations, and protein-peptide
      separations. The current technology available and possible future trends in these
      areas are discussed, and also problems to be solved in the future.

PMID- 1374761
TI  - Characterization of serum antibody responses to natural rotavirus infections in
      children by VP7-specific epitope-blocking assays.
AB  - Knowledge of the immune response to rotavirus is crucial for vaccine development.
      We compared an epitope-blocking assay (EBA) that uses VP7-specific monoclonal
      antibodies with neutralization assays (NAs) with polyclonal antisera for
      detecting serum antibody responses after natural rotavirus infection in children.
      Twenty-six serum pairs from children living in an orphanage with and without
      symptoms during two rotavirus outbreaks were evaluated for VP7 type 1-, 2-, 3-,
      and 4-specific antibody responses. In the first outbreak, which was caused by a
      VP7 type 3 strain, homotypic antibody responses were detected in 11 of 11
      symptomatic children by NA and in 10 of 11 symptomatic children by EBA.
      Heterotypic antibody responses were detected more frequently (12 of 15 children)
      by NA than by EBA, and the heterotypic epitope-blocking antibody responses
      occurred in children older than 14 months of age. Antibody responses in
      asymptomatic children were more commonly detected by EBA than by NA. EBA results
      from the sera of children in the second outbreak indicated that it was caused by
      VP7 type 4, whereas NA results suggested it was caused by VP7 type 3. Our results
      confirm that EBA is a sensitive and specific method for determining VP7 type
      specific immune responses after natural rotavirus infections.

PMID- 1374762
TI  - Protein composition of the hepatitis B virus e antigen in the natural course of
      disease and following interferon therapy.
AB  - The protein composition of hepatitis B virus (HBV) e antigen (HBeAg) in serum was
      analyzed for 63 viremic patients with chronic HBV and found to consist of
      polypeptides with molecular masses of 16, 18, and 20 kDa (P16e, P18e, and P20e,
      respectively). Several experiments demonstrated their viral nature and HBeAg
      specificity and that P16e occurs either in free soluble form or as aggregates or
      immunocomplexes, while P18e and P20e occur essentially as immunocomplexes. Of 63
      patients, 45 (71%) had P16e, P18e, and P20e, and the remaining 18 (29%) had only
      P16e. During the natural history of the disease, spontaneous clearance of HBV DNA
      and HBeAg took place only in six of nine (67%) patients with the three HBe
      polypeptides but in none of the five patients having P16e alone (P less than
      0.05). Similarly, 22 of 23 (96%) patients responding to interferon therapy had
      P16e, P18e, and P20e, but these polypeptides occurred in only 14 of 26 (54%)
      nonresponder patients (P less than 0.001). Following the loss of HBV DNA and
      HBeAg, before the development of anti-HBe, the only HBe species detected were
      P18e and P20e, but these became no longer detectable after complete normalization
      of liver function tests. Therefore, persistence of P16e represents a failure to
      recover from HBV, and the appearance of HBe polypeptides P18e and P20e is
      associated with virus clearance and a favorable outcome of the disease.

PMID- 1374763
TI  - Serotoninergic, noradrenergic, and peptidergic innervation of Onuf's nucleus of
      normal and transected spinal cords of baboons (Papio papio).
AB  - We have investigated with light and electron microscope immunocytochemistry the
      aminergic and peptidergic innervation of Onuf's nucleus in adult baboons. This
      nucleus, located in the ventrolateral part of the sacral spinal cord (S2 and S3),
      is considered to control urethral and anal sphincters and penile muscles. By
      comparison of intact and transected spinal cords, we have found that
      serotoninergic innervation has two origins: first, supraspinal, innervating the
      whole nucleus, with a possible predominance in the dorsal half; and second,
      intraspinal, corresponding to the ventral half of the nucleus. Thyrotropin
      releasing hormone innervation appears largely coincident with serotonin, both in
      intact and transected spinal cords. Noradrenaline is exclusively of supraspinal
      origin, as attested by its disappearance below the level of the section.
      Substance P, calcitonin gene-related peptide, and Leu- and Met-enkephalin, which
      profusely innervate Onuf's nucleus, are on the contrary not affected by the
      transection. They most likely originate from the cord itself or the dorsal root
      ganglia. Thus, Onuf's nucleus innervation in the baboon arises both from
      supraspinal and intraspinal sources. The present study provides an anatomical
      basis for both voluntary and reflex controls of excretory and sexual functions in
      a primate. The same neurotransmitter (serotonin) according to its cell origin and
      discrete topography could exert different influences upon the same effector
      system.

PMID- 1374764
TI  - Ultrastructure of hyaline, border, and vacuole cells in chick inner ear.
AB  - The sense organ for hearing in birds, the basilar papilla, is capable of
      replacing lost or damaged hair cells and supporting cells through regeneration.
      Potential candidates for precursor-cell populations include cells within the
      auditory receptor epithelium and nonsensory cells inferior to the sensory
      epithelium. Ultrastructural characteristics of hyaline cells, border cells, and
      vacuole cells, nonsensory cells which border or lie inferior to the receptor
      epithelium proper, were studied with transmission electron microscopy. Data were
      obtained from normal neonatal and adult chickens. Several rows of epithelial
      cells separate hyaline cells from inferiorly located organ supporting cells and
      hair cells. Ultrastructural characteristics and location of these epithelial
      cells differentiate them from organ supporting cells and hyaline cells;
      consequently, we have termed them "border cells." Synaptic specializations are
      observed between neural elements and border cells, and gap junctions are found
      between adjacent border cells, between border cells and neighboring organ
      supporting cells, and between juxtaposed border and hyaline cells. Hyaline cells,
      in contrast to border cells, are highly specialized. Dense bundles of filaments
      are present in hyaline cells from the basal one-half of the papilla, and an
      unusual structure, a rough tubular aggregate, is present in hyaline-cell
      cytoplasm. Pre- and postsynaptic specializations are observed between neural
      elements and hyaline cells, and gap-junctional complexes link neighboring hyaline
      cells. Vacuole cells lie inferior to the hyaline cells and rest on the inferior
      fibrocartilaginous plate. They are unspecialized morphologically. Their only
      remarkable morphological feature is the abundance of spherical vacuoles within
      their cytoplasmic matrix.

PMID- 1374765
TI  - The dorsal, posterodorsal, and ventral tegmental nuclei: a cyto- and
      chemoarchitectonic study in the human.
AB  - In order to verify the existence of the ventral and posterodorsal tegmental
      nuclei and to extend previous findings regarding the dorsal tegmental nucleus in
      the human brainstem, studies were conducted using cyto- and chemoarchitectonics,
      and computer reconstruction techniques. Serial sections of five brainstems from
      adults with no known neurological disorders were stained for Nissl substance,
      acetylcholinesterase, and substance P. The topography, cytoarchitecture, and
      acetylcholinesterase reactivity of the tegmental nuclei were presented in a mini
      atlas depicting sections cut in transverse and sagittal planes. The dorsal and
      posterodorsal tegmental nuclei were identified fully within the central grey
      matter while the ventral tegmental nucleus extended across the medial
      longitudinal fasciculus into the pontine reticular formation. The dorsal
      tegmental nucleus featured a cell-poor pericentral part, strongly positive for
      acetylcholinesterase, and a central part comprised of densely packed small
      neurons that displayed moderate acetylcholinesterase reactivity and strong
      substance P-like immunoreactivity. The posterodorsal tegmental nucleus, located
      in the same transverse plane as the rostral part of the motor nucleus of the
      trigeminal nerve, was composed of diffusely arranged small to medium neurons with
      its neuropil displaying moderate acetylcholinesterase reactivity and strong
      substance P-like immunoreactivity. The ventral tegmental nucleus, identified as a
      prominent structure in the pontine tegmentum immediately rostral to the genu of
      the facial nerve, contained predominantly large neurons and displayed intensive
      acetylcholinesterase reactivity and substance P-like immunoreactivity. These
      studies showed that the tegmental nuclei, which displayed distinctive cyto- and
      chemoarchitectonic features, were fully present in adult human brainstem.

PMID- 1374766
TI  - Neurons of the human retina: a Golgi study.
AB  - Golgi techniques have been applied to post mortem specimens of human retina.
      Analysis was possible on 150 human retinas processed and viewed by light
      microscopy as wholemounts. Camera lucida drawings and photography were used to
      classify the impregnated neurons into 3 types of horizontal cell, 9 types of
      bipolar cell, 24 basic types of amacrine cell, a single type of interplexiform
      cell, and 18 types of ganglion cell. We have distinguished two types of midget
      bipolar cell: fmB (flat) and imB (invaginating). In central retina, both types
      are typically single-headed, each clearly contacting a single cone. Peripherally,
      they may be two- or even three-headed, obviously contacting more than one cone.
      Two types of small-field diffuse cone bipolars occurring as flat and invaginating
      varieties are found across the entire retina from fovea to far periphery. The
      single rod bipolar type appears about 1 mm from the fovea and increases in
      dendritic tree diameter from there into the far periphery. The putative "ON
      center" blue cone bipolar and the giant bistratified bipolar first described by
      Mariani are also present in human retina and we add two previously undescribed
      bipolar cell types: a putative giant diffuse invaginating and a candidate "OFF
      center" blue cone bipolar. Taking into account the variation of cell size with
      eccentricity at all points on the retina, we observed three distinct varieties of
      horizontal cell. The HI is the well known, long-axon-bearing cell of Polyak. HII
      is the more recently described multibranched, wavy-axoned horizontal cell. The
      third variety, HIII, introduced here, has been separated from the HI type on
      morphological criteria of having a larger, more asymmetrical dendritic field and
      in contacting 30% more cones than the HI at any point on the retina. Amacrine
      cells proved to be most diverse in morphology. Many of the amacrine cell types
      that have been described in cat retina (Kolb et al., '81: Vision Res. 21; 1081
      1114) were seen in this study. Where there are no equivalent cells in cat, we
      have adopted the descriptive terminology used by Mariani in monkey retina. Thus
      eight varieties of small-field amacrines (under 100 microns dendritic trees),
      eight varieties of medium-field cells (100-500 microns dendritic span), and eight
      large-field varieties (over 500 microns dendritic trees) have been classified.
      Often a broadly described variety of amacrine cell can be subdivided into as many
      as three subtypes dependent on stratification levels of their dendrites in the
      inner plexiform layer.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1374767
TI  - Immunohistochemical organization of the ventral lateral geniculate nucleus in the
      ground squirrel.
AB  - The ventral lateral geniculate nucleus (vLGN) of the thirteen-lined ground
      squirrel (Citellus tridecemlineatus) is a highly differentiated nucleus that is
      divisible into five major subdivisions on the basis of retinal projections and
      cytoarchitecture. To pursue the likelihood that these subdivisions (the dorsal
      cap, intergeniculate leaflet, external magnocellular lamina, internal
      magnocellular lamina, and parvicellular segment) correlate with the functional
      diversity of this complex, the present study examined the neurochemical
      composition of the vLGN with regard to substances that have previously proved
      useful in distinguishing functionally distinct subregions within nuclei (i.e.,
      neuropeptide Y (NPY), substance P (SP), leucine and methionine enkephalins, gamma
      aminobutyric acid (GABA), cytochrome oxidase (CO), acetylcholinesterase (AChE),
      and NADPH-diaphorase). The results showed a clear differential neurochemical
      distribution within the nucleus. Neuropeptide Y immunoreactive perikarya were
      found predominantly in the intergeniculate leaflet and external magnocellular
      lamina, with only a few present in the internal magnocellular lamina and dorsal
      cap, and none observed in the parvicellular segment. NPY+ fibers, however, were
      present in all divisions except the parvicellular segment. The highest
      concentration of SP immunoreactive cells was observed in the internal
      magnocellular lamina, and substantial numbers also were scattered in the external
      magnocellular lamina and parvicellular segment. SP+ fibers were seen
      predominantly in the intergeniculate leaflet and the magnocellular laminae. The
      heaviest concentration of enkephalinergic fibers occurred in the internal
      magnocellular lamina and dorsal cap, but fibers were also observed in the
      external magnocellular lamina and intergeniculate leaflet. GABA reactivity was
      widespread throughout the vLGN, with the dorsal cap and external magnocellular
      lamina most heavily labeled, followed by the intergeniculate leaflet and the
      internal magnocellular lamina. Cytochrome oxidase, AChE, and NADPH-diaphorase
      histochemistry revealed rich reactivity within the dorsal cap, and external and
      internal magnocellular laminae and paler reactivity in the intergeniculate
      leaflet and parvicellular segment. The external magnocellular lamina was more
      reactive for CO and NADPH-diaphorase than AChE, while the internal magnocellular
      lamina showed the opposite pattern of reactivity. In addition, NADPH-diaphorase
      reactive cells were present in caudal intergeniculate leaflet and lateral
      external magnocellular lamina. These local differences in the neurochemical
      character of the vLGN support its parcellation into multiple subdivisions. Taken
      in conjunction with the differences in cytoarchitecture and retinal projections,
      these results suggest substantial functional diversity within the ventral lateral
      geniculate complex.

PMID- 1374768
TI  - Differential cholinergic innervation within functional subdivisions of the human
      cerebral cortex: a choline acetyltransferase study.
AB  - The distribution of cholinergic fibers in the human brain was investigated with
      choline acetyltransferase immunocytochemistry in 35 cytoarchitectonic
      subdivisions of the cerebral cortex. All cortical areas and all cell layers
      contained cholinergic axons. These fibers displayed numerous varicosities and, on
      occasion, complex preterminal profiles arranged in the form of dense clusters.
      The density of cholinergic axons tended to be higher in the more superficial
      layers of the cerebral cortex. Several distinct patterns of lamination were
      identified. There were also major differences in the overall density of
      cholinergic axons from one cytoarchitectonic area to another. The cholinergic
      innervation of primary sensory, unimodal, and heteromodal association areas was
      lighter than that of paralimbic and limbic areas. Within unimodal association
      areas, the density of cholinergic axons and varicosities was significantly lower
      in the upstream (parasensory) sectors than in the downstream sectors. Within
      paralimbic regions, the non-isocortical sectors had a higher density of
      cholinergic innervation than the isocortical sectors. The highest density of
      cholinergic axons was encountered in core limbic structures such as the
      hippocampus and amygdala. These observations show that the cholinergic
      innervation of the human cerebral cortex displays regional variations that
      closely follow the organization of information processing systems.

PMID- 1374769
TI  - Light and electron immunocytochemical localization of AMPA-selective glutamate
      receptors in the rat brain.
AB  - Since four AMPA-type excitatory amino acid receptor subunits have been cloned
      recently, it is now possible to localize these important molecules in the nervous
      system. A comprehensive study of AMPA receptor immunocytochemistry was carried
      out on vibratome sections of rat brain, which were immunolabeled with antibodies
      made against peptides corresponding to the C-terminal portions of AMPA-receptor
      subunits: GluR1, GluR2/3, and GluR4. Labeling was most prominent in forebrain
      structures such as the olfactory bulb and tubercle, septal nuclei, amygdaloid
      complex, hippocampus, induseum griseum, habenula, and interpeduncular nucleus,
      and in the cerebellum. Different patterns of immunolabeling were evident with the
      antibodies to the four subunits, with marked contrast between densely and lightly
      stained structures with antibody to GluR1, widespread dense staining with
      antibody to GluR2/3, and moderate staining with antibody to GluR4. In the
      parietal cortex, some non-pyramidal neurons were more densely stained than
      pyramidal cells with antibodies to GluR1. Neurons of the main olfactory bulb,
      other than granule cells, were most densely stained with antibody to GluR1. In
      the cerebellum, Bergmann glia were densely stained with antibodies to GluR1 and
      4, while neurons, other than granule cells, were most densely stained with
      antibody to GluR2/3. Immunolabeling patterns of all antibodies were consistent
      with that of previous in situ hybridization histochemistry studies and with the
      overall pattern of 3H-AMPA binding. Electron microscopy of thin sections taken
      from immunolabeled vibratome sections of hippocampus and cerebral cortex showed
      staining which was restricted mainly to postsynaptic densities and adjacent
      dendritoplasm, and to neuron cell body cytoplasm. We saw no convincing examples
      of stained presynaptic terminals, and only limited evidence of glial staining,
      excepting Bergmann glia.

PMID- 1374770
TI  - [Changes in the cuticle of a keratin fiber under the action of a low-temperature
      plasma].
AB  - Oxygen and air low-temperature plasma treatment leads to significant changes in
      fibre cuticle cell membrane (skin flakes). Both lipids and proteins were
      destroyed. The processes of intensive lipid oxidation resulted from low
      temperature plasma action. This factor seems to change critical surface tension,
      wetting and increasing penetration of dyes through the cuticle.

PMID- 1374771
TI  - Cutaneous histamine metabolism in chronic urticaria.
AB  - Impaired metabolism of histamine in the skin of patients with chronic idiopathic
      urticaria (CIU) might explain the observed enhanced and prolonged skin responses
      to intradermal histamine. Histamine metabolism was measured in homogenates from
      unaffected forearm skin in nine patients with CIU and in skin of age- and sex
      matched control subjects with a radiochromatographic assay, and the results are
      expressed as nanograms of histamine metabolized per milligram of protein per
      hour. Endogenous histamine content was determined by RIA. There was a highly
      significant increase in endogenous histamine content in the skin of patients with
      urticaria (407.8 +/- 188.3 ng/mg of protein) compared with that in skin of
      control subjects (240.0 +/- 73.0 ng/mg of protein) (mean +/- 1 SD; p less than
      0.02), which suggests either an increase in mast cell number or histamine
      concentration per cell. No significant difference was observed in the metabolism
      of histamine between patient and control group; therefore, an alternative
      mechanism may underlie differences in skin reactivity to histamine.

PMID- 1374772
TI  - Cytokines in symptomatic asthma airways.
AB  - To determine whether cytokines are generated in vivo in subjects with asthma, we
      have measured cytokine levels (tumor necrosis factor [TNF], granulocyte
      macrophage-colony-stimulating factor [GM-CSF], interleukin [IL]-1 alpha, IL-1
      beta, IL-2, IL-4, and IL-6) in the airways of subjects with symptomatic (N = 24)
      and asymptomatic (N = 9) asthma with immunoassays (GM-CSF, IL-1 alpha, IL-1 beta,
      IL-2, and IL-4) or bioassays (TNF and IL-6) and the polymerase chain reaction (IL
      1 beta and TNF). Significant levels of TNF (578 +/- 917 pg/ml versus 24 +/- 29
      pg/ml) (p = 0.01), GM-CSF (24 +/- 41 pg/ml versus less than 8 pg/ml) (p = 0.02),
      and IL-6 (225 +/- 327 pg/ml versus 7 +/- 12 pg/ml) (p = 0.01), but not IL-1 alpha
      or IL-4, were detected in the bronchoalveolar lavage fluid (BALF) of patients
      with symptomatic compared with BALF of patients with asymptomatic asthma. Levels
      of IL-1 beta (266 +/- 270 pg/ml versus less than 20 pg/ml) (p = 0.001) and IL-2
      (1.4 +/- 2.8 ng/ml versus less than 0.3 ng/ml) (p = 0.05) in BALF in patients
      with symptomatic compared with that in BALF levels in patients with asymptomatic
      asthma suggested activation of alveolar macrophages and T cells. Thus, in
      episodes of asthma, several cytokines, including TNF, GM-CSF, IL-1 beta, IL-2,
      and IL-6 are detectable in BALF.

PMID- 1374773
TI  - Role of sodium in mediator release from human basophils.
AB  - We studied the effect of extracellular sodium concentration on histamine release
      (HR) from human basophils initiated by immunologic and nonimmunologic stimuli. We
      found that lowering extracellular sodium markedly enhances HR induced by an
      immunologic stimulus from these cells. In buffer in which sodium had been
      replaced with univalent ions of strong bases, enhancement of HR increased as
      extracellular sodium decreased. Enhancement was the result of increased duration
      of release. When sucrose was used for replacement of sodium, we also observed
      that enhancement of HR increased as extracellular sodium decreased, but there was
      some lessening of enhancement at [Na+]e between 5 and 10 mmol/L. Ouabain, which
      is an inhibitor of the Na+/K+ adenosine triphosphatase, and bumetanide and
      furosemide, which are inhibitors of Cl(-)-dependent Na(+)-K+ cotransport, caused
      small increases in enhancement of HR by sodium-deficient buffers; 4,4'
      diisothiocyanostilbene-2-2'-disulfonic acid, an anion transport inhibitor, caused
      some inhibition of enhancement of HR. Analogues of amiloride, such as 5-(N-N
      hexamethylene) amiloride (HMA) and 5-(N-4-chlorobenzyl)-2'-4'dimethylbenzamil
      (CBDMB), inhibit Na+/H+ exchange, Na+/Ca++ exchange, and Na+ channels.
      Interestingly, at higher doses, HMA and CBDMB caused marked enhancement of HR in
      both normal and sodium-deficient buffers. These results suggest that several
      cellular regulatory mechanisms potentially are important for normal basophil
      secretion. The most likely are pH regulatory mechanisms that include Na+/H+
      exchange and anion exchangers that transport alkaline equivalents. Our findings
      enhancement of basophil HR by HMA and CBDMB is particularly noteworthy in light
      of the recent interest in use of amiloride by inhalation for therapy of lung
      disease in patients with cystic fibrosis.

PMID- 1374774
TI  - Immunohistological characterization of mucin epitopes by pre-treatment of gastro
      intestinal sections with periodic acid.
AB  - Periodate pretreatment of paraffin sections of ethanol-fixed gastrointestinal
      mucosae was used to characterize the carbohydrate or peptidic nature of mucin
      epitopes by immunoperoxidase. Immunoreactivity of monoclonal antibodies (MAbs)
      against histo-blood group related carbohydrate epitopes such as A, Lea, Lec,
      Sialosyl Lea, H type 2, I, T, Tn and sialosyl Tn dramatically decreased or even
      disappeared after periodate pretreatment of deparaffinized sections. In contrast,
      the immunoreactivity of MAbs against peptide mucin epitopes such as the gastric
      M1 mucin epitopes was almost unaffected by this treatment. Moreover, periodate
      treatment revealed cryptic peptide M1 mucin epitopes and the peptide MUSE11
      epitope associated with the 20 amino acid tandem repeat (PDTRPAPGSTAPPAHGVTSA).
      An increase of cross-reactions of anti-human M1 MAbs with gastric epithelium of
      different vertebrate species was detected with periodate treatment. Our results
      suggest that this method can be useful for preliminary characterization of the
      biochemical nature of mucin epitopes (peptidic or saccharidic) and for demasking
      peptidic tumour markers which are hidden by saccharide molecules in normal
      tissues.

PMID- 1374775
TI  - An improved ELISA with linear sweep voltammetry detection.
AB  - An improved ELISA combined with linear sweep voltammetry detection of p
      nitrophenol generated by an enzyme has been investigated in this study. p
      nitrophenol, produced from alkaline phosphatase catalysing p-nitrophenyl
      phosphate, yielded an oxidative peak at 1.06 V (vs. Ag/AgCl) with a wax
      impregnated tubular graphite anode. Without separation, the small three-electrode
      system was directly inserted in the well of an ELISA plate for detection. The
      detection limit for p-nitrophenol was 1 x 10(-6) M, lower than that obtained by
      measuring the absorbance of p-nitrophenol. The feasibility of utilizing linear
      sweep voltammetry as a detection scheme was demonstrated by determining
      metallothionein, granulocyte-colony stimulating factor and Xenopus laevis keratin
      using the above new system. The method was simple, reproducible and much more
      sensitive than traditional spectrophotometry.

PMID- 1374776
TI  - Production of anti-peptide specific antibody in mice following immunization with
      peptides conjugated to mannan.
AB  - In order to investigate the usefulness of polysaccharides as carriers for the
      induction of antibody to synthetic peptides, peptides representing residues 139
      147 of the surface antigen of hepatitis B and residues 129-140 of the pre-S2
      region of the protein were coupled to mannan and dextran via an aminocaproic
      spacer molecule. Of the two conjugates studied, only mannan was useful as a
      carrier for the efficient production of anti-peptide antibodies.

PMID- 1374777
TI  - Comparison of four DNA staining fluorescence dyes for measuring cell
      proliferation of lymphokine-activated killer (LAK) cells.

PMID- 1374778
TI  - Expression of functional antigens on neutrophils. Effects of preparation.
AB  - We have studied how different conditions of cell labelling and isolation affect
      the expression of five functional antigens on neutrophils from healthy subjects.
      Fluorescein isothiocyanate conjugated (FITC) antisera specific for the C3bi
      receptor CR3 (CD11b), aminopeptidase N (CD13), the LPS:LPS binding protein
      receptor (CD14) and the receptors for human IgG (Fc gamma RII CDw32 and Fc gamma
      RIII CD16) were incubated with (i) unfixed whole blood at 4 degrees C and at room
      temperature (RT, approximately 20 degrees C), and the leukocytes prepared for
      analysis using the Coulter Q-Prep system, (ii) leukocytes which had obtained
      following the removal of erythrocytes from whole blood by dextran sedimentation
      and which had been washed or left unwashed at RT, and (iii) leukocytes which had
      been prepared from whole blood that had been formaldehyde fixed immediately
      following venesection. The amount of fluorescence associated with the cells was
      determined by flow cytometry. The expression of CD14 was low under all
      conditions. However the expression of CD11b, CD16 and CDw32 was significantly
      higher (p less than 0.05) on neutrophils obtained by dextran sedimentation (n =
      4) than on cells which had been fixed with formaldehyde ex vivo; the increase in
      expression was even greater if the cells had been washed. In contrast, the
      expression of CD13 on formaldehyde fixed cells was higher than on cells which had
      been labelled at 4 degrees C or at room temperature and was similar to or
      slightly lower than that on cells obtained by dextran sedimentation. Increasing
      the time between 10 and 60 min for which the whole blood was incubated with
      antisera at RT or at 4 degrees C, resulted in progressive increases in the
      expression of CD11b and CD13. When neutrophils which had been obtained by dextran
      sedimentation were incubated with unlabelled antibodies to CD16 or CDw32 and FITC
      labelled antibodies to CD11b there was a marked increase in the expression of
      CD11b. Altogether these findings indicate that the analysis of functional
      molecules on neutrophils (which may be rapidly up-regulated during activation)
      should be performed under clearly defined and controlled conditions. Dual
      fluorescence studies may, in some circumstances, produce misleading results.

PMID- 1374779
TI  - Mycoplasma contamination in human leukemia cell lines. I. Comparison of various
      detection methods.
AB  - The sensitivity and reliability of seven assays for mycoplasma detection were
      tested on a panel of leukemia cell lines. The assays used were: microbiological
      cultivation on broth and agar, immunofluorescent visualization of mycoplasmal DNA
      using DAPI (both direct staining and after multiplication of the contaminants on
      an indicator cell line), a nucleic acid hybridization assay with a radioactive
      probe specific for mycoplasmal rRNA, and ELISA with mycoplasma-specific
      polyclonal antibodies, a biochemical method utilizing 6-MPDR, and a mycoplasma
      specific monoclonal antibody in immunofluorescence staining. The broth-agar
      method, the two DAPI tests and the RNA hybridization assay produced the highest
      detection rates; a number of false-negative cases were recorded by the other
      tests. The detection rates, costs, requirement for specialized equipment and
      other characteristics were evaluated for each method. Since each technique also
      has disadvantages and certain limitations and since no method can be regarded as
      the 'gold standard', at least two procedures should be used in routine screening
      for mycoplasma in cell cultures.

PMID- 1374780
TI  - Co-expression of human T cell receptor chains with mouse CD3 on the cell surface
      of a mouse T cell hybridoma.
AB  - In this study we demonstrate that human T cell receptor (TcR) chains can be co
      expressed with murine CD3 on the cell surface of a murine T cell hybridoma. Human
      TcR alpha and beta genes from the Jurkat leukaemic cell line were transfected
      into a TcR-negative mouse T cell hybridoma, TG40. The Jurkat TcR was successfully
      co-expressed at the cell surface with mouse CD3 components. Brightly staining
      transfectants were selected by fluorescence-activated cell sorting, and levels of
      expression comparable to a normal T cell line were achieved suggesting that the
      human TcR dimer assembled efficiently with the mouse CD3 complex. Northern blot
      analysis demonstrated similar levels of TcR messenger RNA to those found in the
      parental Jurkat line. Although we have not formally demonstrated surface
      expression of the Jurkat TcR alpha chain, the residual alpha gene transcript
      which is present in murine TG40 line is non-expressible. In order to test the
      signalling capacity of this human/mouse complex, the transfectants were
      stimulated with an anti-V beta 8 monoclonal antibody. This stimulus led to
      interleukin-2 production by the transfectants, demonstrating the delivery of a
      transmembrane signal. In addition, B10.A mice were immunised with the
      transfectants, and the antisera from these mice stained the transfectant and the
      Jurkat cell line, but not the parental T cell hybridoma. This interspecies
      transfection approach should now permit us to explore the requirements for T cell
      activation, the constraints on TcR alpha beta chain pairing, and creates ideal
      reagents for inducing a mouse anti-human TcR-specific response with a view to
      producing panels of anti-human TcR monoclonal antibodies.

PMID- 1374781
TI  - The natural history of infection with hepatitis C virus (HCV) in chimpanzees:
      comparison of serologic responses measured with first- and second-generation
      assays and relationship to HCV viremia.
AB  - The sensitivity of first- and second-generation tests for antibody to hepatitis C
      virus (HCV) and the relationship among the patterns of antibody response and HCV
      viremia were examined in serial serum samples from 6 chimpanzees experimentally
      infected with HCV and followed less than or equal to 3 years. HCV infection was
      transient in 4 chimpanzees and became chronic in 2. All chimpanzees developed
      antibodies to HCV detectable by second-generation assays, while only 5 of the 6
      became positive by first-generation assay. Second-generation were consistently
      more sensitive than first-generation assays for the early diagnosis of primary
      HCV infection. The pattern observed with second-generation assays was not
      influenced by the outcome of HCV infection, since antibodies remained
      persistently detectable throughout follow-up regardless of whether viremia was
      transient or persistent. In contrast, the first-generation antibody response was
      variable: It usually disappeared after loss of viremia, whereas its presence
      paralleled HCV viremia in chimpanzees with chronic infection.

PMID- 1374782
TI  - Reactivities of an anti-CEA peptide monoclonal antibody.
AB  - Synthetic peptides representing different areas of the CEA molecule were used as
      immunogens for the development of anti-CEA antibodies. Both polyclonal and
      monoclonal antibodies were generated using peptides composed of CEA amino acid
      positions 99-128 and 585-613, respectively. One MAb, designated CP4, generated
      using the CEA peptide 99-128, was chosen for a more detailed analysis of
      reactivity. MAb CP4 reacts in solid phase RIAs with CEA peptide 99-128 immunogen
      and purified native CEA. CP4 did not react with purified non-specific cross
      reacting antigen (NCA), even though there were two single amino acid differences
      between NCA and CEA in the 29 amino acid peptide. The affinity constants of CP4
      for the CEA peptide 99-128 and native CEA are 4.07 x 10(9) M-1 and 5.75 x 10(8) M
      1, respectively. When CP4 was reacted with purified CEA in Western blotting
      experiments, the Mr 180,000 glycoprotein characteristic of CEA was detected, but
      CP4 reacted to various size entities in tumor cell extracts. The results of
      liquid competition RIAs showed that the epitope that MAb CP4 recognized on native
      CEA is not available for binding when CEA is in solution. Physical (adsorption to
      a solid matrix) or chemical (deglycosylation or formalin-fixation) alteration of
      CEA is required for binding of CP4 to CEA. MAb CP4 reacted approximately 1,000
      fold greater to deglycosylated CEA than native CEA. Immunohistochemical studies
      using formalin-fixed paraffin-embedded tissue sections demonstrated that, among
      carcinomas, CP4 reacts selectively with colorectal carcinomas, while normal colon
      is negative. Although stomach carcinoma is negative, dysplastic lesions and areas
      of intestinal metaplasia are reactive. Two of 7 normal stomach tissues showed
      focal cytoplasmic reactivity of the surface epithelium. CP4, therefore, appears
      to react with an epitope with highly restricted expression in colorectal
      carcinoma. These studies demonstrate the complexities in dealing with an anti
      peptide MAb with reactivity to an epitope which is accessible only under certain
      conditions.

PMID- 1374783
TI  - Study of a soluble tumor-associated marker composed of CEA related molecules
      recognized by three monoclonal antibodies.
AB  - Three MAbs, MLuC2, MLuC8 and MLuC9, directed against a molecule that is produced
      and secreted by carcinoma cells were studied with the aim of developing a double
      determinant immunoradiometric assay (DDIRMA). We demonstrated by means of
      immunoblotting, immunodepletion and DDIRMA techniques, that MLuC9 reacted against
      the CEA molecule, whereas MLuC2 and MLuC8 reacted against a 90 Kd molecule
      related to CEA. The DDIRMA performed with the anti-CEA as a catcher MAb and the
      anti-90 Kd as a tracer MAb was found to be positive with the HT29 soluble
      extract, which suggests the existence of CEA/90 Kd dimeric molecules. The same
      reactivity was found when sera from patients with lung carcinomas were tested,
      which excludes that this molecule could be an artefact due to the cell
      solubilization procedures. The association between CEA and the 90 Kd molecule was
      further confirmed by immunodepletion experiments in which the immunoprecipitation
      with one MAb not only removed the recognized molecule, but also partially
      immunodepleted the material from the other.

PMID- 1374784
TI  - Transforming growth factor-alpha expression in benign and malignant human
      prostatic disease.
AB  - Investigation of biological variables in prostatic disease may not only prevent
      patients with a good prognosis being overtreated, but allow better selection of
      appropriate therapy, and may identify potential targets for novel therapies. This
      study investigates the growth factor transforming growth factor-alpha (TGF alpha)
      expression in benign and malignant prostatic biopsies using both radioimmunoassay
      and immunohistochemistry, considering its role in malignant epithelial
      transformation and as a prognostic indicator. Biochemical methods were less
      satisfactory than the more selective immunohistochemical methods, due to the
      heterogeneity of prostatic tissue. Seventy-one percent of benign biopsies (range
      0-18.62ng/mg DNA) and 69% of malignant biopsies (range 0-11.1ng/mg DNA) had
      detectable levels of TGF alpha using radioimmunoassay. Immunohistochemical
      staining for TGF alpha identified expression in 15% of benign (4 out of 27) and
      53% malignant biopsies (18 out of 34). Positive staining was also identified in
      premalignant lesions and within stromal elements, thus implying the factor's role
      in autocrine/paracrine growth and/or malignant transformation. Immunostaining for
      TGF alpha may enhance detection of premalignant lesions and small foci of
      malignant glands which are otherwise difficult to identify using standard
      histopathological techniques.

PMID- 1374785
TI  - Effect of protease inhibitor FUT-175 on acute hemorrhagic pancreatitis in mice.
AB  - The effect of FUT-175, a new synthetic trypsin inhibitor, was evaluated in a
      lethal model of acute hemorrhagic pancreatitis induced by feeding mice a choline
      deficient, ethionine-supplemented diet (CDE diet). When FUT-175 was given
      prophylactically at doses of 20 mg/kg body wt, the survival rate was
      significantly improved (p less than 0.05). The serum amylase concentration and
      trypsin activity in serum were also significantly diminished (p less than 0.05).
      Prophylactic administration of 5 mg/kg body wt of FUT-175 showed a statistically
      significant decrease in the serum trypsin activity, but it did not improve the
      survival rate. Therapeutic administration of FUT-175 showed no favorable effect.
      FUT-175 showed protective effects on the course of severe acute pancreatitis only
      when given prophylactically at the beginning of the pancreatitis induced by the
      CDE diet.

PMID- 1374786
TI  - Simultaneous measurement of cholecystokinin-stimulated amylase release and
      cholecystokinin receptor binding in rat pancreatic acini.
AB  - In the past, isolated-dispersed pancreatic acini have been used to examine either
      cholecystokinin-stimulated amylase release or pancreatic acinar cholecystokinin
      receptors. We have developed and validated a method for simultaneous measurement
      of synthetic cholecystokinin octapeptide-stimulated (CCK8-stimulated) pancreatic
      amylase release and cholecystokinin receptors. After an 18-hour fast, rats were
      killed and their pancreatic acini isolated. Three-milliliter aliquots of acinar
      suspension were incubated for 60 minutes in N-2-hydroxyethylpiperazine-N'-2
      ethanesulfonic acid-Ringer buffer containing graded doses of CCK8 and a constant
      amount (7 pmol/L) of iodine 125-labeled CCK8 (by the Bolton-Hunter method)
      ([125I]BH-CCK8). A 1 ml sample was removed from each flask for determination of
      amylase release, and the remaining 2 ml were used to determine cholecystokinin
      receptor capacities and affinities. The median effective dose for amylase release
      was 16 pmol/L, and release was maximal at 100 pmol/L CCK8 plus 7 pmol/L [125I]BH
      CCK8, a dose that released 28% +/- 3% of total cellular amylase content. High
      affinity (equilibrium dissociation constant of high-affinity receptors = 58 +/- 8
      pmol/L, receptor density of high-affinity receptors = 4 +/- 1 fmol/mg protein)
      and low affinity (equilibrium dissociation constant of low-affinity receptors = 7
      +/- 2 nmol/L, receptor density of low-affinity receptors = 313 +/- 108 fmol/mg
      protein) cholecystokinin receptors were measured. The results demonstrate that
      CCK8-stimulated amylase release and cholecystokinin receptor binding in
      pancreatic acini can be measured concurrently and that the parameters of amylase
      release and cholecystokinin receptor binding are strikingly similar to those
      previously observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374787
TI  - Inhibition of the activation of Hageman factor (factor XII) by aprotinin
      (Trasylol)
AB  - Aprotinin (Trasylol; Bayer AG, Leverkusen, Germany), a protease inhibitor
      resembling or identical with Kunitz' pancreatic trypsin inhibitor, is said to
      have anticoagulant properties, but these are not clearly defined. The present
      study provides evidence that one action of aprotinin is inhibition of the
      activation of Hageman factor (factor XII).

PMID- 1374788
TI  - The zona pellucida binds the mature form of an oviductal glycoprotein
      (oviductin).
AB  - The use of a monoclonal antibody (MAb) specific for the oviductal zona pellucida
      (ZP) of the hamster has demonstrated that a new antigen (oviductin) is acquired
      by the ZP during transit of the oocyte in the oviduct. The epitope that is
      recognized by the MAb bears a terminal N-acetyl-D-galactosamine residue. We
      conducted a study in order to determine whether this immunoreactivity of the
      oviductal ZP results from the addition of the terminal sugar residue to a
      preformed ZP protein or from the transfer of the mature glycoprotein produced by
      oviductal secretory cells. We measured the incorporation of [35S]methionine into
      proteins using four different incubation systems: cumulus oophorus (CO) alone, CO
      in the presence of oviductal fluid, CO co-incubated with empty oviducts, and CO
      within intact oviducts. At the end of the incubation period, the ZP, vitelli,
      dispersed cumulus without oocyte, oviducts, and culture medium were isolated and
      analyzed for their protein content by sodiumdodecylsulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), autoradiography, and immunodetection. The cumulus
      cells synthesized several proteins, independently of the oviductal environment;
      however, none of these proteins corresponded to oviductin. The ZP and the vitelli
      of cumulus oophorus that were incubated either alone or in the presence of
      oviductal fluid did not contain radioactive oviductin. When the oviduct (empty or
      intact) was present in the incubation system, radiolabeled oviductin was
      synthesized and secreted into the incubation medium. The ZP picked up a
      detectable amount of radioactive antigen only in the system in which intact
      oviducts were incubated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374789
TI  - Tissue-specific and dietary control of alpha-amylase gene expression in the adult
      midgut of Drosophila melanogaster.
AB  - The regulatory effects of allelic substitution at the trans-acting mapP locus and
      of dietary glucose on the expression of the duplicate genes for alpha-amylase
      (Amy) in Drosophila melanogaster were examined in the anterior midgut and
      posterior midgut regions of mature flies. The levels of amylase activity and
      amylase protein, as well as the abundance of amylase-specific RNA, were
      quantified. All 3 parameters of Amy expression were concordant. Results indicate
      that the effects of both mapP and dietary glucose are exerted at the level of
      amylase RNA. However, the tissue-specific effects of mapP are restricted to the
      posterior midgut and can therefore be distinguished from the effects of glucose
      in food medium, which influences amylase RNA levels in both the anterior and
      posterior midgut regions. Our data suggest that, in large part, strain-specific
      effects of dietary glucose can be explained on the basis of alternate alleles at
      the mapP locus in different homozygous strains of flies. Levels of amylase RNA in
      tissue extracts of flies from an amylase-null strain were also measured. Low
      levels were observed in both anterior and posterior midgut extracts. These were
      unresponsive to dietary conditions.

PMID- 1374790
TI  - In vitro allogeneic cytotoxicity in the solitary urochordate Styela clava.
AB  - Hemocytes from the solitary urochordate Styela clava can effect allogeneic
      cytotoxicity in vitro. Spectrophotometric and microscopic quantification of eosin
      y dye exclusion revealed significantly greater frequencies of cell death in
      allogeneic hemocyte cultures when compared to autogeneic controls. This cytotoxic
      response was characterized by 1) transient activity such that specific
      cytotoxicity could be detected for only 4 hours of culture though continued
      specific killing may have been obscured by spontaneous cell death; 2) a necessity
      for cellular interaction demonstrated by the elimination of allogeneic
      cytotoxicity in the absence of cell contact; 3) killing of multiple targets by
      effector cells due to high levels of response at low allogeneic ratios; 4)
      insensitivity to altered temperature; 5) increased cytotoxicity in the absence of
      autologous plasma; 6) an absence of xenogeneic reactivity; 7) the presence of
      three hierarchical levels (low, intermediate, and high) of response. These data
      reflect events involved in the recognition of allogeneic cellular determinants
      resulting in specific cytotoxicity effected by immunocompetent cells. Such in
      vitro recognition and cytotoxic recognition and cytotoxic reactivity may be
      responsible for adaptive reactions caused by histoincompatibility in solitary
      tunicates.

PMID- 1374791
TI  - Sequence analysis of an HIV-1 isolate which displays unusually high-level AZT
      resistance in vitro.
AB  - Multiple mutations in the reverse transcriptase (RT) gene were observed in a drug
      resistant isolate of human immunodeficiency virus type 1 (HIV1) from an
      individual having prolonged (greater than 2 years) zidovudine (AZT) therapy. The
      virus replicated in PBMC's in the presence of very high concentrations of AZT
      (125 microM). Drug-sensitive strains were curtailed by 0.01 microM AZT. Eleven
      defined mutations were observed as compared with published sequences of RT for
      eight strains of HIV1. Eight of these mutations were found in the domain involved
      in nucleotide recognition and enzyme function. Only one of the mutations, giving
      a Thr--Tyr change at amino acid 215, matched those previously ascribed (67, 70,
      215, and 219) to the generation of high-level resistance to AZT. Therefore
      additional amino acid changes may have significance in the emergence of super
      resistant viruses.

PMID- 1374792
TI  - Electrodermal orienting response and central nervous system dopamine and
      serotonin activity in schizophrenia.
AB  - The present study was designed to examine the relationship between electrodermal
      activity and the levels of the dopamine metabolite homovanillic acid (HVA) and
      the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal
      fluid. Lumbar cerebrospinal fluid from 36 unmedicated and six medicated
      schizophrenic patients and 23 controls was analyzed by gas chromatograph-mass
      spectrometer. The schizophrenic patients and a group of 14 normal controls were
      presented with a series of orienting tones (1000 Hz, 80 db, 2-second duration)
      while electrodermal activity was monitored. For the patients, this occurred
      during an acute episode of schizophrenia. The results suggest an inverse relation
      between electrodermal activity and the CSF-level of HVA. Although the picture is
      not entirely consistent, electrodermal nonresponders appear to have normal HVA
      levels, while electrodermal responders have decreased levels compared with normal
      controls. There is also a relation between electrodermal activity and 5-HIAA, but
      this association is not as clear-cut as the one between electrodermal activity
      and HVA.

PMID- 1374793
TI  - The Charcot-Bouchard aneurysm controversy: impact of a new histologic technique.
AB  - For over a century a controversy has existed about the prevalence and
      significance of Charcot-Bouchard (C-B) aneurysms, especially regarding their
      relationship to intracerebral hemorrhage (ICH) in man. We reassessed C-B
      aneurysms by staining thick brain sections from 35 hypertensives and 20
      normotensives with the alkaline phosphatase (AP) endothelial stain followed by
      light microscopy and high-resolution microradiography. Charcot-Bouchard aneurysms
      were conspicuously absent in both groups which included four cases of
      hypertensive ICH. The three-dimensional perspective and enhanced ability to trace
      vessels with these techniques helped to identify arteriolar coils and twists that
      can be mistaken for aneurysms when demonstrated by injection methods. Routine
      brain pathologic sections from 2,800 autopsies over a decade showed rare examples
      of parenchymal aneurysms. We conclude that elimination in our study of a)
      injection artifacts and b) misinterpretations shows that C-B aneurysms are
      uncommon and have little relationship to ICH. Despite this, and in view of the
      original contribution of Charcot and Bouchard, the occasional examples of brain
      parenchymal aneurysms should continue to bear their names.

PMID- 1374794
TI  - A non-toxic method for the demonstration of gliosis.
AB  - Neuropathology laboratories have traditionally relied upon the Holzer method for
      demonstration of gliosis. However, concerns about the toxicity of aniline oil
      have markedly reduced the application of this method in recent times.
      Immunostains for glial fibrillary acidic protein (GFAP) are excellent for showing
      gliosis in grey matter but cannot distinguish normal from abnormal astrocytes in
      the white matter. The traditional phosphotungstic acid hematoxylin (PTAH) method
      stains myelin as well as glial fibers and, thus, is not useful for recognizing
      areas of gliosis. Here we present a method for the routine demonstration of
      gliosis based on a modification of Mallory's PTAH method. The staining of myelin
      is eliminated by increasing the concentration of potassium permanganate to 5%
      (from 0.25-1% in traditional methods). The use of aminoalkylsilane adhesive
      ensures that the sections do not detach during the procedure. Areas of gliosis
      stand out against a pale background because only abnormal astrocytes and their
      processes are stained, both in grey and white matter. The method minimizes the
      use of toxic chemicals and can be completed within an eight hour work day in any
      routine neurohistology laboratory, using formalin fixed, paraffin-embedded
      tissue.

PMID- 1374795
TI  - Research--a neglected area of palliative care.

PMID- 1374796
TI  - Reduction of Langerhans cells in smokeless tobacco-associated oral mucosal
      lesions.
AB  - Localized absence of epithelial Langerhans cells (LC) has been shown to affect
      systemic immune responses, allow microbial colonization and play a possible role
      in carcinogenesis. Because use of smokeless tobacco is associated with abnormal
      oral mucosal changes and development of carcinoma, we examined lesion and control
      specimens from 17 current users of smokeless tobacco to determine whether lesions
      showed changes in LC number or antigen expression. We identified LC by
      immunohistochemistry with antibodies to the antigens T6, HLA-DR, HLA-DQ, and HLA
      DP. Lesion specimens contained fewer LC (means of 6 LC/mm and 10 LC/mm2) than did
      the corresponding control specimens (means of 14 LC/mm and 30 LC/mm2), and in
      each pair of lesion and autologous control specimens the reduction in LC was on
      average 58% (range, 3% to 95%). There were no apparent differences between lesion
      and control specimens in the number of LC expressing each of the four marker
      antigens. Reductions in LC occurred in all types of smokeless tobacco-associated
      lesions, regardless of increased epithelial thickness or changes in
      keratinization. Our data indicate that smokeless tobacco reduces the number of
      Langerhans cells at its site of contact with the oral mucosa.

PMID- 1374797
TI  - Immunohistochemical demonstration of enamel proteins in odontogenic tumors.
AB  - Immunohistochemical localization of two enamel proteins, amelogenin and enamelin,
      in comparison with that of keratin, was determined in odontogenic tumors and the
      allied lesions in order to verify functional differentiation of the tumor cells
      as ameloblasts. Amelogenin and enamelin were demonstrated in small mineralized
      foci and in the tumor cells surrounding them in adenomatoid odontogenic tumor
      (AOT), calcifying epithelial odontogenic tumor (CEOT), and calcifying odontogenic
      cyst (COC). Hyaline droplets in AOT showed positive staining for both enamel
      proteins. These mineralized and hyaline materials were not positive for keratin,
      although tumor cells were positive. On the other hand, no immunoreaction for
      enamel proteins was obtained in ameloblastoima and odontogenic epithelial cell
      nests within myxoma and epulis. The results suggest that tumor cells of AOT and
      CEOT and lining epithelial cells of COC show ameloblastic differentiation in
      part, but that ameloblastoma cells do not attain functional matauration as
      secretory phase ameloblasts.

PMID- 1374798
TI  - Patch-clamp recordings of spiking and nonspiking interneurons from rabbit
      olfactory bulb slices: membrane properties and ionic currents.
AB  - Physiological and morphological properties of rabbit, Oryctolagus cuniculus,
      olfactory bulb interneurons were characterized by using a thin slice preparation
      in combination with patch-clamp measurements and Lucifer Yellow fills. Two types
      of interneurons, periglomerular (PG) and juxtaglomerular (JG) cells, were
      unequivocally distinguished in the glomerular layer. Their properties were
      compared to those of mitral cells. PG cells closely resembled previously
      described periglomerular cells in their morphology. During current clamp
      recording these neurons were characterized by their lack of action potentials
      upon depolarization. Consistent with these results no Na+ currents could be
      elicited in voltage clamp experiments. Two types of outward K+ currents were
      distinguished: one which inactivated and one which did not. From their morphology
      JG cells appear to be either short axon cells or external tufted cells. JG cells
      always responded with a single, TTX-blockable action potential in response to
      maintained current injection. Two types of membrane currents were identified in
      JG cells during voltage clamp: a fast, inactivating Na+ current that was fully
      activated at -80 mV, and a sustained outward current that shared some properties
      with a delayed rectifier K+ current. The particular relationship between the
      voltage dependence of the Na+ and K+ currents appeared to preclude repetitive
      spike activity.

PMID- 1374799
TI  - Patch-clamp recordings of spiking and nonspiking interneurons from rabbit
      olfactory bulb slices: GABA- and other transmitter receptors.
AB  - Transmitter receptor ion channels from previously identified rabbit olfactory
      bulb neurons were studied by using a thin slice preparation in combination with
      patch-clamp measurements. PG cells, which closely resembled previously described
      periglomerular interneurons in their morphology, responded to microapplication of
      GABA, acetylcholine, norepinephrine and glycine with the activation of distinct
      ionic currents. JG cells, which belong either to the class of short axon cells or
      external tufted cells, never showed GABA responses. In mitral cells ionic
      currents activated by GABA, acetylcholine, norepinephrine and glutamate could be
      elicited. Further measurements of GABA-activated currents of PG cells were made
      and indicated that these cells expressed two different types of GABA receptors:
      one which showed fast desensitization with a decay time constant of about 5 s,
      and one which slowly desensitized with a decay time constant of about 20-30 s.
      Both types were completely inhibited by bicuculline methiodide (50 microM). GABA
      receptors were not blocked by Zn2+ (0.1 mM). From the dose-response relationship
      of the peak GABA-activated currents, an apparent dissociation constant of 50
      microM was derived. From single channel measurements in excised outside-out
      patches, a single channel conductance of GABA-activated Cl- currents of 24 pS was
      obtained during continuous application of the agonist. Single channel events had
      a mean open time of 1.9 ms.

PMID- 1374800
TI  - Commissural connections mediate inhibition for the computation of interaural
      level difference in the barn owl.
AB  - In the barn owl (Tyto alba), the posterior nucleus of the ventral lateral
      lemniscus (VLVp) is the first site of binaural convergence in the pathway that
      processes interaural level difference (ILD), an important sound-localization cue.
      The neurons of VLVp are sensitive to ILD because of an excitatory input from the
      contralateral ear and an inhibitory input from the ipsilateral ear. A previously
      described projection from the contralateral cochlear nucleus, can account for the
      excitation. The present study addresses the source of the inhibitory input. We
      demonstrate with standard axonal transport methods that the left and right VLVps
      are interconnected via fibers of the commissure of Probst. We further show that
      the anesthetization of one VLVp renders ineffective the inhibition that is
      normally evoked by stimulation of the ipsilateral ear. Thus, one cochlear nucleus
      (driven by the ipsilateral ear) appears to provide inhibition to the ipsilateral
      VLVp by exciting commissurally-projecting inhibitory neurons in the contralateral
      VLVp.

PMID- 1374801
TI  - Binding of hirudin to human alpha, beta and gamma-thrombin. A comparative kinetic
      and thermodynamic study.
AB  - Thermodynamic parameters for the binding of hirudin to human alpha, beta and
      gamma-thrombin have been determined between pH 5.0 and 9.0, and from 10 degrees C
      to 40 degrees C; kinetic data for the association and dissociation of the
      proteinase-inhibitor complex were obtained at pH 7.5 and 21 degrees C. These
      results have been analysed in parallel with the inhibitor-binding properties of
      human alpha, beta and gamma-thrombin for the bovine basic pancreatic trypsin
      inhibitor (Kunitz-type inhibitor; BPTI). For the purpose of an homogeneous
      comparison, values of the apparent association equilibrium constant for BPTI
      binding to human gamma-thrombin have been determined between pH 5.0 and 9.0, at
      21 degrees C. The different binding behaviour of hirudin and BPTI with respect to
      human alpha, beta and gamma-thrombin has been related to the inferred
      stereochemistry of the proteinase-inhibitor contact regions. In particular,
      whereas the beta and gamma-loops play an appreciable role in the stabilization of
      the enzyme-hirudin complexes, they contribute to impairment of the adduct
      formation for the proteinase/BPTI system.

PMID- 1374802
TI  - Both forms of translational initiation factor IF2 (alpha and beta) are required
      for maximal growth of Escherichia coli. Evidence for two translational initiation
      codons for IF2 beta.
AB  - The gene infB codes for two forms of translational initiation factor IF2; IF2
      alpha (97,300 Da) and IF2 beta (79,700 Da). IF2 beta arises from an independent
      translational event on a GUG codon located 471 bases downstream from IF2 alpha
      start codon. By site-directed mutagenesis we constructed six different mutations
      of this GUG codon. In all cases, IF2 beta synthesis was variably affected by the
      mutations but not abolished. We show that the residual expression of IF2 beta
      results from translational initiation on an AUG codon located 21 bases downstream
      from the mutated GUG. Furthermore, two forms of IF2 beta have been separated by
      fast protein liquid chromatography and the determination of their N-terminal
      sequences indicated that they resulted from two internal initiation events, one
      occurring on the previously identified GUG start codon, the other on the AUG
      codon immediately downstream. We conclude that two forms of IF2 beta exist in the
      cell, which differ by seven aminoacid residues at their N terminus. Only by
      mutating both IF2 beta start codons could we construct plasmids that express only
      IF2 alpha. A plasmid expressing only IF2 beta was obtained by deletion of the
      proximal region of the infB gene. Using a strain that carries a null mutation in
      the chromosomal copy of infB and a functional copy of the same gene on a
      thermosensitive lysogenic lambda phage, we could cure the lambda phage when the
      plasmids expressing only one form of IF2 were supplied in trans. We found that
      each one of the two forms of IF2, at near physiological levels, can support
      growth of Escherichia coli, but that growth is retarded at 37 degrees C. This
      result shows that both forms of IF2 are required for maximal growth of the cell
      and suggests that they have acquired some specialized but not essential function.

PMID- 1374803
TI  - Swirls, wrinkles and the whole ball of wax (the source of keratin in cerumen).
AB  - Recent work carried out at the Ear Pathology Research Laboratory has demonstrated
      that cerumen plugs consist of a large amount of keratin debris. In this study the
      site of origin of this keratin was investigated. This was done by histologically
      examining these cerumen plugs without disturbing the natural relationship between
      the plug and the surrounding epithelium. We have clearly demonstrated that a
      cerumen plug consists of keratin arising from the migratory epithelium of the
      deep external auditory canal and epithelium of the superficial external auditory
      canal.

PMID- 1374804
TI  - Role and specificity of T-cell subsets in spontaneous recovery from Friend virus
      induced leukemia in mice.
AB  - Spontaneous recovery from Friend virus complex-induced leukemic splenomegaly in H
      2Db/b mice correlated with the appearance of Friend virus complex-specific
      cytotoxic T lymphocytes (CTL) detectable directly in spleen cell populations. By
      testing CTL on target cells containing expression vectors encoding individual
      retroviral structural proteins, the main viral protein recognized was shown to be
      the Friend murine leukemia helper virus envelope glycoprotein. In vivo depletion
      of CD8-positive T cells drastically reduced the incidence of recovery, providing
      direct evidence for the role of CD8-positive CTL in the spontaneous recovery
      process. In vivo depletion of CD4-positive cells had little effect on the early
      stages of recovery but did cause a marked reduction in the final incidence of
      recovery at 60 to 90 days. Thus, CD8-positive cells were required for the
      initiation of the recovery process, whereas CD4-positive cells appeared to be
      required for maintenance of the recovered status.

PMID- 1374805
TI  - Preventive effects of early anti-CD4 or anti-CD8 treatment on Borna disease in
      rats.
AB  - Borna disease is a virus-induced, immunopathological encephalomyelitis in which
      CD4+ cells and macrophages dominate the pathological picture. However,
      significant numbers of CD8+ cells have been morphologically identified in
      perivascular infiltrates as well. To determine the contribution of different T
      cell subsets to the pathogenesis of Borna disease, virus-infected rats were
      treated with monoclonal antibodies specific for CD4+ and CD8+ cells. Both types
      of monoclonal antibodies were able to significantly decrease or even prevent the
      local inflammatory reaction in the brain if given early during the infection.
      However, CD8-specific monoclonal antibodies appeared to be more effective than
      antibodies directed against CD4+ cells. Treatment initiated 4 days postinfection
      did not result in inhibition of encephalitis and disease. Virus titers in the
      brain of infected rats treated with T-cell-specific antibodies did not differ
      from titers in untreated infected control animals. The results indicate an
      important functional role of CD8+ cells, in addition to CD4+ cells, in the
      pathogenesis of Borna disease.

PMID- 1374806
TI  - Modification of foot-and-mouth disease virus O1 Caseros after serial passages in
      the presence of antiviral polyclonal sera.
AB  - Foot-and-mouth disease virus (FMDV) shows a remarkable antigenic variability and,
      like other RNA viruses, presents a high rate of mutation. It has been proposed
      that selection exerted by antibodies of the host could play a major role in the
      rapid evolution of FMDV. The present work reports the selection of FMDV antibody
      resistant (Nr) populations after serial passages of a cloned FMDV O1 Caseros
      strain on secondary monolayers of bovine kidney cells in the presence of
      subneutralizing antiviral polyclonal sera (APS). After a limited number of
      passages, i.e., 29, under selective pressure, the virus population showed the
      following characteristics: (i) increased resistance to neutralization by APS
      (Nr), (ii) altered electrophoretic mobility of its structural viral proteins
      (VP1), and (iii) alterations at the RNA nucleotide sequence that codes for the
      major antigenic site of VP1. These acquired characteristics were detected at
      passage 15 and remained unmodified throughout successive passages. These results
      document a rapid selection and fixation of specific mutations in response to
      immunological pressure. In addition, the findings that (i) mutations not related
      to APS selection were not detected and (ii) after 29 passages at a high
      multiplicity of infection without immunological pressure, the RNA sequence that
      codes for VP1 remained unmodified clearly demonstrated that FMDV O1 Caseros
      presents in vitro a remarkable unexpected genetic stability.

PMID- 1374807
TI  - Enhancement of the antibody response to flavivirus B-cell epitopes by using
      homologous or heterologous T-cell epitopes.
AB  - We have been investigating the T-helper (Th)-cell response to the flavivirus
      envelope (E) glycoprotein. In our studies with Murray Valley encephalitis (MVE)
      virus, we previously identified synthetic peptides capable of priming Th
      lymphocytes for an in vitro antivirus proliferative response (J. H. Mathews, J.
      E. Allan, J. T. Roehrig, J. R. Brubaker, and A. R. Hunt, J. Virol. 65:5141-5148,
      1991). We have now characterized in vivo Th-cell priming activity of one of these
      peptides (MVE 17, amino acids 356 to 376) and an analogous peptide derived from
      the E-glycoprotein sequence of the dengue (DEN) 2, Jamaica strain (DEN 17, amino
      acids 352 to 368). This DEN peptide also primed the Th-cell compartment in BALB/c
      mice, as measured by in vitro proliferation and interleukin production. The
      failure of some MVE and DEN virus synthetic peptides to elicit an antibody
      response in BALB/c mice could be overcome if a Th-cell epitope-containing peptide
      was included in the immunization mixture. A more detailed analysis of the
      structural interactions between Th-cell and B-cell epitope donor peptides
      revealed that the peptides must be linked to observe the enhanced antibody
      response. Blockage or deletion of the free cysteine residue on either peptide
      abrogated the antibody response. The most efficient T-B-cell epitope interaction
      occurred when the peptides were colinearly synthesized. These Th-cell-stimulating
      peptides were also functional with the heterologous B-cell epitope-containing
      peptides. The Th-cell epitope on DEN 17 was more potent than the Th-cell epitope
      on MVE 17.

PMID- 1374808
TI  - Conformational alteration of Sindbis virion glycoproteins induced by heat,
      reducing agents, or low pH.
AB  - Sindbis virions undergo a conformational rearrangement after attachment to cells
      but prior to entry, as detected by exposure of epitopes on virus-cell complexes
      which are not accessible to their cognate monoclonal antibodies on native virions
      (D. C. Flynn, W. J. Meyer, and R. E. Johnston, J. Virol. 64:3643-3653, 1990). The
      rearrangement did not appear to require transit of virions through a low-pH
      environment, and the altered virions participated in a productive infection. This
      naturally occurring structural alteration could be mimicked, although not
      precisely duplicated, by any of the three artificial treatments of purified
      virions in vitro: brief incubation at 51 degrees C, treatment with 1 to 5 mM
      dithiothreitol, or incubation of pH 5.8 to 6.0. Infectivity was maintained after
      all three treatments, suggesting that Sindbis virions are metastable and can
      exist in at least two infectious conformations. The integrity of external,
      neutralizing epitopes was maintained on cell-associated virions and in the
      altered conformations induced by heat and dithiothreitol, whereas these epitopes
      were unreactive under low-pH conditions that induced an analogous exposure of
      previously inaccessible epitopes. The pH at which the conformational change was
      induced and the pH at which virions could mediate cell-cell fusion from without
      were coordinately shifted when these two parameters were determined for another
      strain of Sindbis virus. This coordinate shift in pH optima suggests that the
      conformational change in virion structure observed at the cell surface may be
      causally related to fusion.

PMID- 1374809
TI  - Human immunodeficiency virus type 1 integration protein: DNA sequence
      requirements for cleaving and joining reactions.
AB  - Using purified integration protein (IN) from human immunodeficiency virus (HIV)
      type 1 and oligonucleotide mimics of viral and target DNA, we have investigated
      the DNA sequence specificity of the cleaving and joining reactions that take
      place during retroviral integration. The first reaction in this process is
      selective endonucleolytic cleaving of the viral DNA terminus that generates a
      recessed 3' OH group. This 3' OH group is then joined to a 5' phosphoryl group
      located at a break in the target DNA. We found that the conserved CA located
      close to the 3' end of the plus strand of the U5 viral terminus (also present on
      the minus strand of the U3 terminus) was required for both cleaving and joining
      reactions. Six bases of HIV U5 or U3 DNA at the ends of model substrates were
      sufficient for nearly maximal levels of selective endonucleolytic cleaving and
      joining. However, viral sequence elements upstream of the terminal 6 bases could
      also affect the efficiencies of the cleaving and joining reactions. The
      penultimate base (C) on the minus strand of HIV U5 was required for optimal
      joining activity. A synthetic oligonucleotide mimic of the putative in vivo viral
      "DNA" substrate for HIV IN, a molecule that contained a terminal adenosine 5'
      phosphate (rA) on the minus strand, was indistinguishable in the cleaving and
      joining reactions from the DNA substrate containing deoxyadenosine instead of
      adenosine 5'-phosphate at the terminal position. Single-stranded DNA served as an
      in vitro integration target for HIV IN. The DNA sequence specificity of the
      joining reaction catalyzed in the reverse direction was also investigated.

PMID- 1374810
TI  - Cross-neutralization of human immunodeficiency virus type 1 and 2 and simian
      immunodeficiency virus isolates.
AB  - In contrast to infrequent and low-titer cross-neutralization of human
      immunodeficiency virus type 1 (HIV-1) isolates by HIV-2- and simian
      immunodeficiency virus (SIV)-positive sera, extensive cross-neutralization of HIV
      2NIH-Z, SIVMAC251, and SIVAGM208K occurs with high titer, suggesting conservation
      of epitopes and mechanism(s) of neutralization. The V3 regions of HIV-2 and SIV
      isolates, minimally related to the HIV-1 homolog, share significant sequence
      homology and are immunogenic in monkeys as well as in humans. Whereas the crown
      of the V3 loop is cross-reactive among HIV-1 isolates and elicits neutralizing
      antibodies of broad specificity, the SIV and especially HIV-2 crown peptides were
      not well recognized by cross-neutralizing antisera. V3 loop peptides of HIV-2
      isolates did not elicit neutralizing antibodies in mice, guinea pigs, or a goat
      and together with SIV V3 peptides did not inhibit serum neutralization of HIV-2
      and SIV. Thus, the V3 loops of HIV-2 and SIV do not appear to constitute simple
      linear neutralizing epitopes. In view of the immunogenicity of V3 peptides, the
      failure of conserved crown peptides to react with natural sera implies a
      significant role of loop conformation in antibody recognition. Our studies
      suggest that in addition to their grouping by envelope genetic relatedness, HIV-2
      and SIV are neutralized similarly to each other but differently from HIV-1. The
      use of linear peptides of HIV-2 and SIV as immunogens may require greater
      attention to microconformation, and alternate subunit approaches may be needed in
      exploiting these viruses as vaccine models. Such approaches may also be
      applicable to the HIV-1 system in which conformational epitopes, in addition to
      the V3 loop, participate in virus neutralization.

PMID- 1374811
TI  - Disulfide-bonded discontinuous epitopes on the glycoprotein of vesicular
      stomatitis virus (New Jersey serotype).
AB  - Intrachain disulfide bonds between paired cysteines in the glycoprotein (G) of
      vesicular stomatitis virus (VSV) are required for the recognition of
      discontinuous epitopes by specific monoclonal antibodies (MAbs) (W. Keil and R.
      R. Wagner, Virology 170:392-407, 1989). Cleavage by Staphylococcus aureus V8
      protease of the 517-amino-acid VSV-New Jersey G protein, limited to the glutamic
      acid at residue 110, resulted in a protein (designated GV8) with greatly retarded
      migration by polyacrylamide gel electrophoresis (PAGE) under nonreducing
      conditions. By Western blot (immunoblot) analysis, protein GV8 was found to lose
      discontinuous epitope IV, which maps within the first 193 NH2-terminal amino
      acids. These data, coupled with those obtained by PAGE migration of a vector
      expressed, truncated protein (G1-193) under reducing and nonreducing conditions,
      lead us to postulate the existence of a major loop structure within the first 193
      NH2-terminal amino acids of the G protein, possibly anchored by a disulfide bond
      between cysteine 108 and cysteine 169, encompassing epitope IV. Site-directed
      mutants in which 10 of the 12 cysteines were individually converted to serines in
      vaccinia virus-based vectors expressing these single-site mutant G proteins were
      also constructed, each of which was then tested by immunoprecipitation for its
      capacity to recognize epitope-specific MAbs. These results showed that mutations
      in NH2-terminal cysteines 130, 174, and, to a lesser extent, 193 all resulted in
      the loss of neutralization epitope VIII. A mutation at NH2-terminal cysteine 130
      also resulted in the loss of neutralization epitope VII, as did a mutation at
      cysteine 108 to a lesser extent. Both epitopes VII and VIII disappeared when
      mutations were made in COOH-distal cysteine 235, 240, or 273, the general map
      locations of epitopes VII and VIII. These studies also reveal that distal, as
      well as proximal, cysteine residues markedly influence the disulfide-bond
      secondary structure, which ostensibly determines the conformational structure of
      the VSV-New Jersey G protein required for presentation of the major discontinuous
      epitopes recognized by neutralizing MAbs.

PMID- 1374812
TI  - Altered cell tropism and cytopathicity of feline immunodeficiency viruses in two
      different feline CD4-positive, CD8-negative cell lines.
AB  - Two interleukin-2-dependent feline CD4-positive and CD8-negative cell lines, MYA
      1 and the newly established FeL-039, were used as host cells for infection with
      feline immunodeficiency virus (FIV). All FIV strains used, the Petaluma strain
      and several new isolates, were highly cytopathic to MYA-1. In contrast, the
      kinetics of FIV replication in FeL-039 differed greatly depending on the strain
      tested, i.e., noninfectious strain, highly cytopathic strain, and less cytopathic
      strain producing a persistent state for a long period. It appears, therefore,
      that cell tropism for FIV differed with each FIV strain tested even in T-cell
      lines showing similar cell surface phenotypes. Cytopathicity of FIV is evidently
      due to both the FIV strain and the host T cell.

PMID- 1374813
TI  - Gene for the major antigenic structural protein (p100) of human herpesvirus 6.
AB  - A human herpesvirus 6 (HHV-6) structural protein of 100 kDa (p100) is the
      polypeptide most frequently and intensively reactive in immunoblotting analyses
      with human sera on HHV-6-infected cells or partially purified virions. The gene
      for p100 was identified by screening a bacteriophage lambda library with
      monospecific rabbit antisera. The gene codes for a polypeptide of 870 amino acids
      with a calculated molecular size of 97 kDa. Its amino-terminal third is weakly
      homologous to the immunogenic basic matrix phosphoprotein pp150 of human
      cytomegalovirus. Five fragments representing more than 93% of HHV-6 p100 were
      prokaryotically expressed. The antigenic epitopes of p100 were preliminary mapped
      by immunoblotting with human sera. They are located within the carboxy-terminal
      part which is neither homologous nor cross-reactive to pp150 of human
      cytomegalovirus. Availability of the gene for the immunodominant structural
      protein should provide tools for studies of pathogenesis by HHV-6.

PMID- 1374815
TI  - [Immunoelectron microscopic observations on adhesive proteins and granule
      membrane proteins of platelet alpha-granule].

PMID- 1374814
TI  - Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes:
      from viral latency to replication.
AB  - By using cloning methodology, 13 CD4+, CD8-, CD45RO+, and CD29+ clones, isolated
      from human immunodeficiency virus (HIV)-negative donors, have been characterized
      and tested regarding their susceptibility to two strains of HIV type 1 (HIV-1).
      Infected clones possess integrated provirus. Only six are able to replicate HIV
      1, while seven may normally grow without cytopathic effect and without viral
      replication. These results argue that all CD4+ lymphocyte clones may be
      infectable but that a heterogeneity exists regarding their abilities to replicate
      HIV-1.

PMID- 1374817
TI  - [Plasminogen activator and angiogenesis].

PMID- 1374816
TI  - [Function of GMP-140, a granule membrane protein of platelets].

PMID- 1374819
TI  - [A case of lung cancer with Mallory bodies].
AB  - This paper is a report of a large cell carcinoma (solid carcinoma with mucus
      formation-WHO) which developed in the right upper lobe of a 71-year-old woman and
      in which cytoplasmic Mallory body-like inclusions (MBL) similar to Mallory bodies
      (MB) often found in alcoholic liver disease and hepatocellular carcinoma were
      noted in the tumor cells. MBL was an eosinophilic massive or reticular hyalin,
      and showed staining properties similar to those of MB in general stainings.
      Electron microscopically, it was made up mainly of a fine granular amorphous
      substance with high electron density and was not surrounded by a membrane. A part
      of the margin was in close contact with filaments approximately 10 nm in
      diameter, with tonofibril-like structures around it, which suggested a
      relationship with cytokeratin. On immunoperoxidase staining using a couple of
      cytokeratin antibodies, definitely positive findings were not obtained with MBL
      themselves. MBL of this case basically has the same character as that of MBL
      which appears in fibrous lesions in the lung and MB in liver disease. It was
      concluded that it is necessary to preoperatively distinguish this entity
      cytologically or histologically from pulmonary metastasis of hepatocellular
      carcinoma.

PMID- 1374818
TI  - [Field trial for the early detection of patients with ovarian cancer].
AB  - Six tumor-associated antigens, cancer antigen 125(CA125), tissue polypeptide
      antigen (TPA), ferritin (Fr), carcinoembryonic antigen (CEA), alpha fetoprotein
      (AFP), and sialyl Lex-i(SLX) were measured simultaneously for the early detection
      of ovarian cancer. To decrease both false positive and false negative cases in
      the combination assay, the value of statistical discrimination analysis employing
      the serum values of appropriate tumor markers in detecting ovarian cancer was
      studied by the method of Mahalanobis' generalized distance. The new "ovarian
      cancer screening test" designed by us has been enforced in Shizuoka Prefecture
      since 1988, and 23,307 serum samples have been analyzed. Of the 165 ovarian
      cancer patients 127 patients were suspected as cancer by such clinical procedures
      as pelvic examination and/or ultrasonography, while 150 patients were detected
      cancer by the statistical discrimination method. Of the 38 patients with ovarian
      cancer overlooked by the clinical procedures 31 could be found by the statistical
      method. We conclude that clinical procedures and the statistical method can be
      complementary in detecting patients with this malignancy.

PMID- 1374820
TI  - Serum amylase values in callitrichids.
AB  - We determined the amylase levels in serum samples from six callitrichid species.
      The normal serum amylase values for all of these species was within or higher
      than the normal human range. Amylase values higher than the normal range occurred
      not only in association with pancreatitis but also pyometra, bone fracture,
      abscesses, diabetes mellitus and gastrointestinal conditions leading to diarrhea.
      We concluded that although serum amylase activity may be helpful in diagnosing
      pancreatitis, it is, as in humans, not specific for this condition in
      callitrichids.

PMID- 1374821
TI  - Comparison of total cellular DNA, mRNA, and rRNA levels between normals and Down
      syndrome patients.
AB  - Two recent studies have suggested that the absolute cellular RNA and/or DNA
      levels in Down syndrome (DS) may be unusual compared to normals and may be linked
      to phenotypic expression (Pash et al., 1990; Dahl et al. 1988). We have extended
      these two studies by directly quantitating and comparing the total cellular mRNA,
      rRNA, and DNA levels in fibroblasts and lymphocytes derived from normal and DS
      individuals. The assay methods used, which allowed us to present the various
      nucleic acids levels in picograms per cell, did not reveal any significant
      difference between the two groups.

PMID- 1374822
TI  - Removal of lipoprotein fraction from culture media corrects the reduction of acid
      sphingomyelinase activity induced by AY9944.

PMID- 1374823
TI  - Mechanism of the nephrogenic repair response. Studies on proliferation and
      vimentin expression after 35S-1,2-dichlorovinyl-L-cysteine nephrotoxicity in vivo
      and in cultured proximal tubule epithelial cells.
AB  - Studies were performed in vivo using 35S-(1,2-dichlorovinyl)-L-cysteine, a
      nephrotoxin that damages the S3 segment of the proximal tubule after metabolism
      to a reactive intermediate. Initiation of damage (35S covalent binding) was
      complete by 6 hour, and an early proliferative response was observed by 24 hour
      in the S2 or S3C segments. Necrosis in the S3M and increased blood urea nitrogen
      were maximal at 48 hours and were accompanied by an increase in proliferation of
      cells at the wound site. Regeneration was marked by the appearance of vimentin
      expressing cells that lacked brush border enzymes. The loss of differentiated
      character in the regenerative epithelium persisted after the proliferation
      (bromodeoxyuridine incorporation) had stopped; redifferentiation occurred between
      days 5 and 13. Much of the process was reproduced by culturing rat kidney
      proximal tubule epithelial cells in defined medium. As growth increased, the
      cells expressed vimentin and lost brush border marker enzymes. However, as the
      cells reached high density and stopped dividing there was an increase in brush
      border markers, as was seen in vivo. Vimentin expression did not decrease,
      however. The data support a mechanism for damage and nephrogenic repair composed
      of 1) interaction of the toxin with the target cells, 2) necrosis and
      exfoliation, 3) loss of differentiation and cell growth, 4) recovery of the
      damaged area and cessation of cell growth, and 5) differentiation of the
      quiescent cells. Nephrogenic repair may have similarities with the
      differentiation of the tubular epithelium during development.

PMID- 1374824
TI  - [Specific prostatic antigen: usefulness in clinical practice].

PMID- 1374825
TI  - [Anti-neutrophil cytoplasmic antibodies].

PMID- 1374826
TI  - [Metabolic changes in a patient in the early phase of acute pancreatitis].
AB  - The present paper reports on the perioperative metabolic changes in a 70-year-old
      female patient in whom an acute (oedematous) pancreatitis occurred during the
      transduodenal excision of a villous adenoma of the duodenal papilla. Since blood
      was taken for metabolic investigations before, during and after surgery, data on
      the changes in the intermediary metabolism during the early phase of acute
      pancreatitis in humans was recorded. Raised activity of the pancreatic enzymes
      amylase and lipase was demonstrable just minutes after extirpation of the
      papillary tumour after intraoperative cholangiography had been performed via a
      choledochotomy. This showed occlusion of the duodenal papilla as well as imaging
      the pancreatic duct. The reflux of bile into the pancreatic duct is considered to
      be one of the causative factors of acute pancreatitis (Opie-syndrome). The
      following metabolic changes were registered at surgery and on the first day
      thereafter: reduction in the serum concentration of cholesterol ester, the
      triglycerides and the phospholipids by 30 to 50% of the preoperative values
      respectively, as well as lactacidaemia (up to 60 mg/dl). At the same time, the
      serum bilirubin concentration and the concentrations of the amino acids alanine
      and glutamate in the serum were temporarily raised. The question is, whether
      these metabolic changes were a direct consequence of the activity of the
      pancreatic enzymes of amino acid and lipid metabolism that were released into the
      blood, or whether reduced synthesis by the liver (lipoproteins, lecithin:
      cholesterol-acyl-transferase) was responsible for these changes.

PMID- 1374827
TI  - Mapping and characterization of the promoter elements of the regulatory nif genes
      rpoN, nifA1 and nifA2 in Rhodobacter capsulatus.
AB  - The promoter elements responsible for the expression of the regulatory nif genes
      rpoN, nifA1 and nifA2 of Rhodobacter capsulatus were mapped by exonuclease-III
      mediated deletions and by primer extension analysis. The rpoN promoter maps 600
      bp upstream of rpoN and has the characteristic features of a -24/-12 promoter.
      The upstream activator sequence (UAS) displays two mismatches with the NIFA
      consensus sequence and is located 37 bp upstream of a perfect -24/-12 promoter
      element. The spacing and/or the helical phasing of these two promotor elements
      was found to be important for promoter function. In addition, an UAS half-site
      may contribute to optimal promoter function. The rpoN UAS can partially
      substitute for the UAS of the nifE promoter. An open reading frame with homology
      to Klebsiella pneumoniae NIFU was identified between the rpoN promoter and rpoN
      and termed nifU2 since another nifU-like gene (nifU1) is located in a
      conventional nifUSVW operon in nif region A. Thus, rpoN, encoding an alternative
      sigma factor for RNA polymerase, is cotranscribed with a nifU analogous gene from
      an rpoN-dependent promoter. Mapping of the promoter elements involved in the
      expression of nifA copy 1 and copy 2 identified a novel promoter type. A
      conserved distal promoter element is likely to represent the binding site of NTRC
      in R. capsulatus. The DNA region preceding the mapped 5' ends of the nifA
      transcripts displays much less homology. The distance between the distal and
      proximal elements is about 100 bp.

PMID- 1374828
TI  - Analysis of the promoters and upstream sequences of nifA1 and nifA2 in
      Rhodobacter capsulatus; activation requires ntrC but not rpoN.
AB  - Transcription of Rhodobacter capsulatus genes encoding the nitrogenase
      polypeptides (nifHDK) is repressed by fixed nitrogen and oxygen. R. capsulatus
      nifA1 and nifA2 encode identical NIFA proteins that activate transcription of
      nifHDK and other nif genes. In this study, we report that nifA1-lacZ and nifA2
      lacZ fusions are repressed in the presence of NH3 and activated to similar levels
      under nitrogen-deficient conditions. This nitrogen-controlled activation was
      dependent on R. capsulatus ntrC (which encodes a transcriptional activator) but
      not rpoN (which encodes an RNA polymerase sigma factor). We have used primer
      extension analyses of nifA1, nifA2 and nifH and deletion analyses of nifA1 and
      nifA2 upstream regions to define likely promoters and cis upstream activation
      sequences required for nitrogen control of these genes. Primer extension mapping
      confirmed that ntrC but not rpoN is required for nifA1 and nifA2 activation, and
      that nifA1 and nifA2 do not possess typical RPON-activated promoters.

PMID- 1374829
TI  - Differential adhesion of granulocytes to five distinct phenotypes of cultured
      microvascular endothelial cells.
AB  - Adhesion of isolated human polymorphonuclear granulocytes (PMNs) to five
      different phenotypes of cultured microvascular endothelial cells derived from
      bovine corpora lutea was investigated by measuring the myeloperoxidase content of
      cell lysates. Untreated and interleukin 1 (IL-1) -pretreated confluent monolayers
      were overlaid with unstimulated and phorbol ester (PMA)-stimulated PMNs in the
      absence and presence of the monoclonal antibody IB4 recognizing and functionally
      blocking beta 2 (CD18) of the leukocyte integrins. Unstimulated PMN adhesion was
      highest on type 4, followed by type 3 and 5 endothelial cells. This adhesion was
      not inhibited by treatment with IB4. IL-1 pretreatment of endothelial cells
      resulted in a significant increase of PMN adhesion on types 1, 2, and 4, most of
      which was also beta 2 integrin-independent. PMA-stimulation of PMNs increased
      adhesion to maximal values on cell types 1 and 5, which was largely blocked by
      IB4. Type 2 endothelial cells supported significantly less PMA-stimulated PMN
      adhesion than all other types. In the presence of IB4, adhesion of PMNs to
      untreated and IL-1-pretreated type 3 and 4 endothelial cells was significantly
      reduced by PMA. This reduction of beta 2 integrin-independent adhesion by PMA
      stimulation is compatible with possible shedding of the lectin-like leukocyte
      adhesion molecule, L-selectin, from PMNs. Differential PMN adhesion may reflect
      distinctive expression of endothelial adhesion molecules in different phenotypes
      of microvascular endothelial cells. Endothelial specialization within the
      microcirculation may have important functional consequences for the inflammatory
      response in vivo.

PMID- 1374830
TI  - Immunoelectron microscopy of Chlamydia psittaci with monoclonal antibodies.
AB  - An immunoelectron microscopic study was performed to determine the distribution
      of antigenic components on particles of Chlamydia psittaci and infected cells
      using a number of monoclonal antibodies (MAbs). Of three anti-lipopolysaccharide
      (LPS) antibodies (4D5, A2 and 4G5), two antibodies (4D5 and A2) reacted with the
      surface of reticulate bodies (RBs) but not with that of elementary bodies (EBs).
      The other antibody (4G5) reacted with both EBs and RBs. Examination of infected
      cells in thin sections revealed that 4D5 and A2 combined with the membranes of
      both EBs and RBs. These results indicate that each LPS epitope localized at a
      different position in the chlamydial membrane. Most MAbs directed to protein
      antigens reacted on the surface of both EBs and RBs though 3E9 specific for the
      90 kDa and 50 kDa protein components combined with RBs only.

PMID- 1374831
TI  - Organization of the ribosomal RNA genes in Treponema phagedenis and Treponema
      pallidum.
AB  - The genomic DNA fragment which contains ribosomal RNA (rRNA) genes for Treponema
      phagedenis was cloned into bacteriophage vector lambda EMBL3. A restriction map
      of the fragment was constructed and the organization of the rRNA genes was
      determined. The fragment contained at least one copy of the 16S, 23S and 5S
      sequences and the genes are arranged in the order 16S-23S-5S. Southern
      hybridization using radiolabeled rRNA gene probes to genomic DNA from T.
      phagedenis strain Reiter and T. pallidum strain Nichols showed that these
      organisms have two radioactive fragments which hybridize to the probes in their
      genome. These results suggest that both pathogenic and non-pathogenic strains of
      Treponema may carry at least two sets of rRNA genes on their chromosomes.

PMID- 1374832
TI  - [The determination of the location of the antigens of the causative agent of
      melioidosis at the ultrastructural level by using monoclonal antibodies].
AB  - The indirect immunoperoxidase method with the use of monoclonal antibodies has
      been employed to determine the localization of antigens of melioidosis agents.
      The formed reaction products were then detected by the electron microscopic
      analysis. The most important in melioidosis pathogenesis antigens 6 and 8 (AG 6
      and AG 8) were determined to localize on the cell wall and in the capsule-like
      mucous layer, respectively. Monoclonal antibodies to AG 8 due to their marked
      cross-linking properties promote stabilization, preservation and detection of
      labile melioidosis agent. At the same time the mucous layer prevents monoclonal
      antibodies to AG 6 to access to the corresponding antigen, localized on the cell
      wall and makes its detection difficult.

PMID- 1374833
TI  - [The C antigen of Francisella tularensis].
AB  - A new envelope antigen C, specific for virulent strains of Francisella
      tularensis, was revealed by immunodiffusion analysis. In contrast to antigens A
      and P this antigen is common for Francisella and Brucella. C-antigenic lipid
      fraction was obtained by chloroform-ethanol (1:1) extraction of bacterial slime.
      This fraction contained carbohydrates (31.6%) without proteins and detected by
      TLC glycolipid, which proved glycolipid nature of C-antigen. Introduction of C
      fraction or alive F. tularensis resulted in accumulation of C. precipitins in
      blood serum.

PMID- 1374834
TI  - [Goiter-inducing substances].

PMID- 1374835
TI  - Some problems in understanding other people: analysing talk in research,
      counselling and psychotherapy.
AB  - Various problems associated with analysing interview transcripts are identified.
      It is asserted that such problems of analysis may also be problems associated
      with understanding other people in counselling and psychotherapy.

PMID- 1374836
TI  - Detection of a CpA methylase in an insect system: characterization and substrate
      specificity.
AB  - A cytosine-specific DNA methyltransferase (EC 2.1.1.37) has been purified to near
      homogeneity from a mealybug (Planococcus lilacinus). The enzyme can methylate
      cytosine residues in CpG sequences as well as CpA sequences. The apparent
      molecular weight of the enzyme was estimated as 135,000 daltons by FPLC. The
      enzyme exhibits a processive mode of action and a salt dependence similar to
      mammalian methylases. Mealybug methylase exhibits a preference for denatured DNA
      substrates.

PMID- 1374837
TI  - Evidence of gonadotropin-releasing hormone mRNA in the rat anterior pituitary.
AB  - We have previously reported the presence and the persistence of immunoreactive
      GnRH cells in the rat anterior pituitary in the absence of exogenous GnRH. To
      substantiate the hypothesis of its endogenous production, we have investigated
      the presence of GnRH mRNA in rat anterior pituitary tissue using a reverse
      transcription-polymerase chain reaction (RT-PCR) amplification protocol. Total
      RNA from rat anterior pituitary, hypothalamus (positive control), and muscle
      (negative control) was reverse transcribed to the first strand of cDNA and
      amplified by PCR using a set of three exon-specific primers for a target sequence
      of the GnRH gene, i.e. two external 5' and 3' primers and one internal 3' primer.
      UV light analysis of the size-fractionated RT-PCR products showed two bands of
      the predicted sizes [511 and 397 base pairs (bp)] hybridizing with GnRH probes in
      Southern analysis only in hypothalamus and in anterior pituitary but not in
      muscle. These two bands were far more intense in the hypothalamus than in the
      anterior pituitary. Restriction enzyme analysis evidenced that the two RT-PCR
      products included the HindIII endonuclease site of cleavage present in the GnRH
      cDNA sequence spanned by the primers, yielding two digested products of the
      anticipated sizes (86 and 425 bp for the 511-bp fragment, and 86 and 311 bp for
      the 397-bp fragment). The complementary sequences for the GnRH probes were
      conserved in the 425-bp and 311-bp fragments. Based on these results, we can
      conclude that the RT-PCR products generated from RNA tissue were the target GnRH
      sequences in the anterior pituitary as well as in the hypothalamus.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1374838
TI  - Ca2+ channel modulation and kinase-C activation in a pituitary cell line:
      induction of immediate early genes and inhibition of proliferation.
AB  - We have studied the interaction between dihydropyridine (DHP) Ca2+ modulators and
      the phorbol ester phorbol 12-myristate 13-acetate (PMA) on whole cell Ca2+
      currents, 45Ca2+ uptake, immediate early gene (IEG) expression, and proliferation
      in the rat pituitary GH4C1 cell line. When short (3- to 5-msec) depolarizing
      voltage clamp steps were used to activate L-type Ca2+ channels, the DHP Ca2+
      agonist (-)Bay K 8644 markedly enhanced Ca2+ entry by slowing channel closing
      upon repolarization. In contrast, the Ca2+ agonist induced only small and
      inconsistent increases in c-fos mRNA and did not measurably increase NGFI-A. Ca2+
      channel activation by depolarization with 50 mM KCl in the presence of (-)Bay K
      8644 induced large increases in 45Ca2+ uptake, but failed to markedly induce
      either of the IEGs. The phorbol ester PMA did not alter T- or L-type Ca2+ current
      or 45Ca2+ uptake by GH4C1 cells, but triggered large increases in both c-fos and
      NGFI-A mRNA. In combination, PMA and (-)Bay K 8644 acted synergistically to
      increase mRNAs for both IEGs. The effect of the DHPs was stereospecific; (+)Bay K
      8644, a Ca2+ antagonist, inhibited PMA-induced increases in c-fos and NGFI-A
      mRNAs. Both PMA and (-)Bay K 8644 inhibited the proliferation of GH4C1 cells,
      measured by cell count or [3H]thymidine incorporation. The inhibition by the Ca2+
      agonist was stereoselective and approximately additive to that of PMA. These
      results indicate that the expression of c-fos IEG and that of NGFI-A IEG are
      differentially regulated by separate second messenger pathways in GH4C1
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374839
TI  - Estrogen sulfotransferase of the rat liver: complementary DNA cloning and age-
      and sex-specific regulation of messenger RNA.
AB  - Mammalian estrogen sulfotransferase (EST; EC 2.8.2.4) sulfurylates the hydroxyl
      group of estrogenic steroids by transferring the sulfate from a cosubstrate
      adenosine 3'-phosphate-5'-phosphosulfate. Sulfurylated steroids do not bind to
      the estrogen receptor with high affinity and, therefore, are hormonally inactive.
      We have purified rat liver EST and developed monoclonal antibody to this enzyme.
      By immunoscreening a lambda gt-11 expression library constructed from male rat
      liver cDNAs, the cDNA clone corresponding to EST was identified and isolated. A
      recombinant expression plasmid (pCMV5) containing this cDNA insert when
      transfected into COS-7 cells generated both immunologically and enzymatically
      active EST. With the help of this cDNA probe, we have explored the regulation of
      the EST mRNA in the liver and the possible role of this enzyme in sex hormone
      action. During the lifespan of male rats, only the young adult animals show
      hepatic androgen responsiveness. Also, estrogenic hormones strongly antagonize
      androgen action in the rat liver. Northern blot analysis of liver RNA derived
      from male rats of different ages shows that the androgen sensitivity of young
      adult animals is associated with a high expression of EST mRNA. During the same
      period, mRNA corresponding to dehydroepiandrosterone sulfotransferase is markedly
      (approximately 10-fold) down-regulated. Such a correlation is in concordance with
      the role of these enzymes in the maintenance of hepatic androgen sensitivity
      during young adult life by inactivating the estrogenic and sparing the androgenic
      steroids. Furthermore, the increase in the hepatic androgen sensitivity of
      androgen-treated female rats is also associated with the induction of
      EST.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1374840
TI  - Localisation of three epitopes of the env protein of feline immunodeficiency
      virus.
AB  - The envelope protein of the feline immunodeficiency virus (FIV) was analyzed
      using several epitope prediction programs based on profiles of hydrophilicity,
      antigenicity, and probability of residues to lie on the protein surface.
      Tentative homologies with the immunodominant epitope sites in simian virus (SIV)
      or human immunodeficiency virus (HIV) such as the V3 loop, the site of cleavage
      between surface envelope protein (SU) and transmembrane envelope protein (TM),
      and sites of N-glycosylation were thus identified. Five peptides corresponding to
      potential epitopes were synthesized. Four out of five peptides (P99, P100, P101,
      P103) were from the FIV surface envelope protein (SU). The last one (P102) was
      from the FIV transmembrane envelope protein TM. Three of these peptides (P99,
      P100, and P102) were recognized in ELISA by almost all the sera from infected
      cats. The peptide from TM (102) was recognized by sera from both naturally
      infected and inoculated cats, whereas peptides P99 and P100 (from SU) were
      recognized mainly by sera from naturally infected cats. On the basis of these
      results we propose that peptides P99, and P100 from SU and P102 from TM
      constitute epitopes on the FIV env protein.

PMID- 1374841
TI  - Expression and structure of serum gp70 as an acute phase protein in NZB mice.
AB  - A cDNA corresponding to a serum gp70 synthesized as an acute phase protein in
      mouse hepatocytes was cloned and analyzed. This cloned cDNA had the
      characteristics of an endogenous xenotropic murine leukemia virus. Synthesized
      oligo-DNA specific for this cDNA reacted strongly with liver RNA derived from NZB
      mice injected with LPS as a trigger of an acute phase inflammatory response.
      There was also low level of gp70 in the kidney in response to LPS injection. The
      LTR structure of the cDNA showed that this clone is the immediate precursor of an
      infectious xenotropic virus in the proposed evolutionary scheme of murine
      leukemia virus.

PMID- 1374842
TI  - Epitope mapping of anti-breast and anti-ovarian mucin monoclonal antibodies.
AB  - Anti-breast cancer antibodies (BC2, HMPV and 4B6) and an anti-ovarian cancer
      antibody (OM1) were found to react with mucins--indeed with the protein core
      encoded by the MUC1 gene. This gene contains a VNTR (variable number of tandem
      repeats) encoding a 60 bp (= 20 amino acids) repeat sequence and within this
      amino acid sequence SAPDTRPAP was predicted, by hydrophilicity analysis, to be
      the immunogenic peptide sequence. The four antibodies were shown to react with
      MUC1 VNTR encoded peptides in direct binding and inhibition studies. The precise
      reactivity of the 4 mAbs was mapped using ELISA in both solid and liquid phase,
      and demonstrated the epitopes to be: APDTR (BC2 and HMPV), PDTR (4B6) and DTRPA
      (OM1). By using the pepscan method, the epitopes were shorter (PDTR, DTR and
      DTRP). However when these short peptides (except DTR) were synthesized they did
      not react; flanking amino acids are needed for the epitopes. Clearly several
      different methods should be used to define the reactive epitope. Within (S)APDTR,
      major amino acid substitutions could be made--even of three to four amino acids
      without altering antibody binding, provided that P and R were not substituted. It
      was of interest that an anti-ovarian cancer antibody gave similar anti-peptide
      reactions to the anti-breast cancer antibodies; apparently MUC1 peptides in
      ovarian cancer are the same as in breast cancer.

PMID- 1374843
TI  - The effect of orientation of epitopes on the immunogenicity of chimeric synthetic
      peptides representing measles virus protein sequences.
AB  - We have studied the influence of the orientation of T- and B-cell epitopes on the
      immunogenicity of chimeric synthetic peptides in terms of the ability of the T
      cell epitope to provide help for the production of antibody to the B-cell
      epitope. A T-cell epitope from the fusion protein of measles virus (288-302),
      previously shown to act as a T-helper epitope in a panel of six inbred mouse
      strains, was co-linearly synthesized at either the amino- or carboxyl- terminus
      of a B-cell epitope from the haemagglutinin of the virus (188-199) with or
      without the inclusion of a glycine-glycine spacer. The four chimeric peptides
      were used to immunize a panel of five mouse strains and induced good anti-chimera
      antibody responses. In general, the chimeras in which the T-cell epitope was
      amino-terminal to the B-cell epitope induced antibodies which bound well to the B
      cell epitope whereas the carboxyl-terminal orientation of the T-cell epitope with
      respect to the B-cell epitope failed to induce such antibody. These latter
      chimeras induced the production of antibodies which preferentially bound to the T
      cell epitope. The inclusion of the gly-gly spacer in the chimeras did not enhance
      their immunogenicity nor did it increase antibody titres to the B-cell epitope.
      The affinity of the anti-peptide antibodies was markedly influenced by the
      orientation of the epitopes in the chimeras. The antibody elicited by the peptide
      in which the T-cell epitope was amino terminal to the B-cell epitope had
      significantly higher affinity for the B-cell epitope than that induced by
      immunization with the peptide in the reverse orientation.

PMID- 1374844
TI  - Localization of sequence-determined neoepitopes and neutrophil digestion
      fragments of C-reactive protein utilizing monoclonal antibodies and synthetic
      peptides.
AB  - We recently described 17 anti-CRP mAb, seven to native- (or conformational) and
      10 to neo- (or sequence-determined) epitopes, including several anti-neo-CRP mAb
      specific for CRP peptide 199-206. In the present study, four new anti-native- and
      four new anti-neo-CRP mAb were generated and characterized by ELISA reactivity
      with native and modified human and rabbit CRP, as well as binding to pronase
      fragments of human CRP in Western blots. Assays with 17 synthetic CRP peptides
      identified anti-neo-CRP mAb specific for peptides 1-16, 14-24 and 137-152,
      respectively. The anti-neo-CRP mAb were reacted with fragments obtained by
      digesting CRP with multiple additional enzymes, including Staphylococcal V8
      protease, trypsin, elastase, plasmin, thrombin and alpha-chymotrypsin. Native CRP
      was remarkably resistant to enzymic digestion, particularly in the presence of
      calcium, but was readily cleavable upon denaturation. Twenty-three informative
      fragments served to further distinguish mAb reactivity with at least four
      additional neo-CRP epitopes, which presumptively included residues in the regions
      of amino acids 22-45, 41-61, 114-121 and 130-138, respectively. The eight
      epitopes identified corresponded well with predicted regions of CRP antigenicity.
      In addition, at least six distinct native or conformation-determined epitopes
      were delineated. Reactivity of the anti-neo-CRP mAb with fragments of CRP
      generated by PMN enzymes indicated that regions sensitive to cleavage by
      neutrophil enzymes are located at approximately 3, 10 and 16 kD from the amino
      terminus of the CRP subunit. We expect that the anti-CRP mAb described and mapped
      herein will be useful tools for the elucidation of CRP structure and function.

PMID- 1374845
TI  - Sensitivity and single-strand DNA break repair in Chinese hamster mutants exposed
      to the carcinogen aflatoxin B1 epoxide and its dichloride model.
AB  - Aflatoxin B1 (AFB1) is a potent carcinogen and mutagen. It requires metabolic
      activation to be converted to the DNA-binding product aflatoxin B1 epoxide (AFB1
      epoxide). A model of this epoxide is aflatoxin B1 dichloride (AFB1Cl2). Both
      react at the N7 position of guanine to form large adducts. The major adduct
      formed can either be rapidly removed to leave an apurinic site or can undergo
      ring opening of the imidazole ring to form a chemically stable adduct. A number
      of Chinese hamster DNA repair-deficient mutants have been screened for their
      sensitivity to AFB1-epoxide and AFB1Cl2. Some of the mutants screened belong to
      different UV complementation groups. Human genes involved in nucleotide excision
      repair correct deficiencies found in these complementation groups. The mutants
      which were found to be most sensitive to AFB1 (V-C4 and V-H1) were further
      investigated. Alkaline elution was used to measure AFB1-induced DNA single-strand
      break repair in the mutants. V-H1 repaired completely in 24 h whereas V-C4
      displayed only partial repair.

PMID- 1374846
TI  - Properties of a monoclonal antibody for the detection of abasic sites, a common
      DNA lesion.
AB  - The abasic site is one of the most frequent changes occurring in DNA and has been
      shown to be lethal and mutagenic. An abasic site in DNA can be tagged by reaction
      with O-4-nitrobenzylhydroxylamine (NBHA), resulting in the formation of an oxime
      linkage between the abasic site and the NBHA moiety. In order to measure NBHA
      tagged abasic sites, a monoclonal antibody was elicited against a 5'
      phosphodeoxyribosyl O-4-nitrobenzyl hydroxylamine-BSA conjugate. The antibody was
      specific for the NBHA residue as demonstrated by hapten inhibition, with IC50
      values for 5'-phosphodeoxyribosyl-NBHA, deoxyribosyl-NBHA, ribosyl-NBHA and NBHA
      of 0.3 microM, 5 microM, 5 microM and 7 microM, respectively. Other haptens
      examined, including benzylhydroxylamine, 5'-phosphodeoxyribosyl-, deoxyribosyl-,
      and ribosyl-benzylhydroxylamine, showed no inhibition even at 1 mM. The antibody
      showed high specificity for NBHA-modified AP sites in DNA and exhibited no cross
      reactivity with normal DNA bases, otherwise-modified DNA bases or unmodified AP
      sites. Using a direct ELISA assay, the antibody detected 1 AP site (after NBHA
      modification) per 10,000 base-pairs or approximately 10 femtomoles of AP sites in
      DNA. DNA lesions were detectable in 60Co gamma-irradiated DNA at a dose as low as
      10 rad (0.1 Gy) and the production of antibody detectable sites was proportional
      to the gamma-ray dose. Since NBHA reacts with lesions containing an aldehyde
      group, the simplicity and sensitivity of the antibody assay should provide a
      useful method for the quantitation of AP sites or other DNA lesions containing an
      aldehyde group.

PMID- 1374847
TI  - Molecular cloning and DNA sequencing of the radC gene of Escherichia coli K-12.
AB  - The radC102 mutation that sensitizes E. coli K-12 cells to ultraviolet light,
      ionizing radiations and alkylating agents was localized between the fpg and pyrE
      genes at 81.7 min on the bacterial chromosome. E. coli strain BH20 (radC+, fpg
      1::KnR) has a 10.5-kb EcoRI/KpnI DNA fragment spanning the region from pyrE to
      the insertion mutation fpg-1::KnR. The proximity of the radC gene to this
      insertion mutation provided a strategy to isolate the radC+ gene based on the
      cloning of radC+ and fpg-1::KnR on the same DNA fragment using the resistance to
      kanamycin as a selector. A library of EcoRI/KpnI DNA fragments of E. coli strain
      BH20 was inserted into pUC19. One recombinant plasmid conferring resistance to
      kanamycin was selected and named pRCV10. The pRCV10 plasmid partially restores
      the resistance to UV-radiation when transformed into SR1187 (radC102), but
      sensitizes the wild-type strain to the same treatment. The radC102 complementing
      region was localized on a 1.2-kb BglII/BglII DNA fragment which was sequenced.
      The DNA sequence complementing the radC102 mutation contained an ATG translation
      start codon with an open reading frame of 297 base pairs which encodes a
      polypeptide of Mr 11,500. The order of the genes in this region of the E. coli
      chromosome is: fpg--rpmBG--radC--pyrE.

PMID- 1374848
TI  - Increased resistance to the toxic effects of alkylating agents in tobacco
      expressing the E. coli DNA repair gene ada.
AB  - The protein coding region of the E. coli gene ada has been transferred to tobacco
      plants by a leaf disc transformation procedure involving an Agrobacterium
      tumefaciens Ti plasmid. Transformed plants were shown to be transgenic for the
      ada message and had increased levels of O6-alkylguanine DNA alkyltransferase
      activity. The N-methyl-N-nitrosourea- or taurinechlorethylnitrosourea-induced
      inhibition of growth of calluses or of cells in suspension was considerably lower
      in ada-transformed than in non-transformed plants. This indicates that O6
      alkylguanine, O4-alkylthymine or phosphotriesters are growth-inhibitory lesions
      in tobacco.

PMID- 1374849
TI  - Evidence for excision repair in promitochondrial DNA of anaerobic cells of
      Saccharomyces cerevisiae.
AB  - The respiratory adaptation (i.e., essentially mitochondrial biogenesis) in the
      excision repair-defective rad3-type mutants of Saccharomyces cerevisiae
      undergoing transition from the anaerobic to the aerobic state is found to be far
      more sensitive to 254-nm ultraviolet radiation (UV) than that of the RAD wild
      type strain. We confirm that mitochondria of aerobic cells of a RAD strain lack
      the excision repair capacity of UV-induced pyrimidine dimers at all doses tested
      (1-15 J/m2). In contrast, in promitochondria of anaerobic cells of the wild-type
      strain excision repair appears to take place. This process is very efficient at
      low doses (at 0.5-5 J/m2 100% of the UV endonuclease-sensitive sites disappear),
      whereas at high doses its efficiency is reduced by about 50%. The
      promitochondrial excision repair of pyrimidine dimers appears to be under nuclear
      control since it is blocked in the rad2 mutant. Finally photoreactivation is
      found to be operating in nuclei, mitochondria and promitochondria.

PMID- 1374850
TI  - International Symposium of the USSR-West Germany on "Biological Membranes.".

PMID- 1374851
TI  - Differential regulation of tyrosine hydroxylase, neuropeptide Y and galanin gene
      expression in the pons and medulla oblongata following chronic oral
      administration of 2% saline: a combined in situ hybridisation and
      immunohistochemical study.
AB  - In situ hybridisation histochemistry and immunohistochemistry was used to study
      the response of the noradrenergic A6 and A2 cell groups in the rat following oral
      administration of 2% saline for 12 days. Messenger ribonucleic acid (mRNA)
      encoding tyrosine hydroxylase and neuropeptide Y increased by 85 and 65%,
      respectively (p less than 0.05) in A6, while levels in A2 were unaltered after
      saline ingestion. The observed changes in mRNA were accompanied by increased
      expression of neuropeptide Y and tyrosine hydroxylase immunoreactivities in A6
      neurons, whereas A2 neurons were unaffected. In contrast, mRNA encoding galanin,
      which is also colocalised with noradrenaline in A6 cells, was unaltered by
      osmotic stimulation. Our results suggest that noradrenaline and neuropeptide Y
      transmitter systems in the A6 group are activated whereas the galanin transmitter
      system remains unaffected during saline ingestion.

PMID- 1374852
TI  - The effects of propofol anesthesia on transcortical electric evoked potentials in
      the rat.
AB  - The effects of halogenated anesthetic agents on somatosensory and motor evoked
      potentials (MEP) have been documented previously. Intravenous anesthetic propofol
      has not yet been used during MEP monitoring. This study investigates the effects
      of propofol on transcortical MEP in rats during bolus, infusion, and recovery
      conditions. After baseline MEP recordings, animals received a hetastarch bolus,
      followed by a propofol (10 mg/kg) bolus dose. A propofol infusion (10 mg/kg/h)
      and a hetastarch infusion were then begun. MEP recordings were obtained after the
      propofol bolus, during the infusion, and after a 30-minute recovery phase. Blood
      pressure readings remained stable. MEP onset latency increased, and amplitude
      decreased. Response duration diminished. All values returned towards the baseline
      during recovery. Our results show that the effects of propofol on MEPs are
      similar to its effects on somatosensory evoked potentials. Propofol seems to be a
      reasonable agent for use during intraoperative MEP monitoring and should be
      further investigated for use during spinal cord monitoring in humans.

PMID- 1374853
TI  - Treatment options in primary Ewing's sarcoma of the spine: report of seven cases
      and review of the literature.
AB  - Primary Ewing's sarcoma of the spine is reviewed, and seven cases are presented.
      Ewing's sarcoma of the spine is a rare condition that appears with a clinical
      triad of local pain, neurological deficit, and a palpable mass. The clinical
      picture, imaging characteristics, and management are discussed. The definitive
      management of Ewing's sarcoma of the spine, as in other locations, could include
      three main modalities: surgery, radiotherapy, and combination chemotherapy. In
      the presence of acute neurological decompensation, decompressive surgery via an
      appropriate approach should be performed. Because Ewing's sarcoma is usually
      sensitive to chemotherapy, initial chemotherapy, in neurologically stable
      patients, could be attempted first without surgical resection. Further management
      could then be gauged according to the response.

PMID- 1374854
TI  - High serum alkaline phosphatase level of meningioma cell origin: case report and
      review of the literature.
AB  - A 13-year-old boy with an anaplastic meningioma at the site of the jugular
      foramen had an increased serum level of aklaline phosphatase (ALPase) (liver
      form) in the serum before surgery. Immediately after excision of the tumor, the
      serum ALPase level decreased dramatically. Histochemical and immunohistochemical
      examinations revealed ALPase activity (liver form) in the neoplastic cells. This
      case would be the third with clinical evidence that the increased level of serum
      ALPase is of neoplastic cell origin from the meningioma. The implications of
      ALPase in brain tumors are discussed.

PMID- 1374855
TI  - Unitary, quantal and miniature GABA-activated synaptic chloride currents in
      cultured neurons from the rat superior colliculus.
AB  - The aim of this study was to identify the conductance change induced by one
      quantum of gamma-aminobutyric acid from axonal release sites on cultured superior
      colliculus neurons. Unitary (single cell-activated) inhibitory postsynaptic
      currents and spontaneous synaptic activity were recorded with patch clamp
      techniques in the whole cell configuration while superfusing the entire neuron
      with normal saline. Miniature inhibitory postsynaptic currents were recorded in
      the presence of tetrodotoxin and in reduced [Ca2+]o/[Mg2+]o. In addition, the
      membrane area contributing to synaptic activity was limited to a narrow window of
      50 microns. Smaller neurons were chosen for recording to render a standard
      deviation of the "instrumental" noise of less than 1.5 pA at a holding voltage of
      -80 mV. After two weeks in vitro, the percentage of synaptically connected tectal
      neurons exceeded 50%. At holding voltages of -80 mV (Cl- equilibrium potential 
      12 mV) minimal amplitudes of unitary inhibitory postsynaptic currents were as low
      as 7-10 pA, while maximal amplitudes exceeded 500 pA. The mean time to peak and
      time constant of decay were 3.0 and 34.4 ms, respectively (n = 31). Fluctuating
      unitary inhibitory postsynaptic currents were deemed to be compound postsynaptic
      responses. Multiple Gaussian equations could be fitted to the amplitude
      histograms of unitary postsynaptic currents. This procedure rendered a quantal
      size between 5.0 and 10.9 pA (mean 7.1 pA; S.D. 1.78 pA) in five neurons from
      mature cultures. The amplitudes of statistically determined quantal inhibitory
      postsynaptic currents were slightly smaller than the independent estimate from
      somatic miniature inhibitory postsynaptic currents. The latter had a mean
      amplitude of 9.1 pA (S.D. 3.3 pA, n = 23), a mean time to peak of 1.65 ms (n =
      9), and a mean time constant of decay of 16.2 ms (n = 9). Single channel
      recording from outside-out patches showed three to four main conductance states
      ranging from 9 to 22 pS. Single channel closures at the 21-24 pS level were
      occasionally observed during relaxation of miniature currents. The small size of
      whole cell quantal inhibitory postsynaptic currents and somatic miniature
      currents indicates that one GABA quantum opened only 5-15 single Cl- channels.

PMID- 1374856
TI  - Choline acetyltransferase- and substance P-like immunoreactive elements in fetal
      striatal grafts in the rat: a correlated light and electron microscopic study.
AB  - Fetal striatal neurons were transplanted into the ibotenic acid-lesioned rat
      striatum. Three months after transplantation, the graft tissue was processed for
      choline acetyltransferase- and substance P-like immunoreactivity and was
      subsequently examined at the light and electron microscopic levels. The study
      demonstrated that choline acetyltransferase- and substance P-like-immunoreactive
      neurons were homogenously present throughout fetal striatal grafts, although in
      decreased numbers compared with those in the normal rat striatum. The majority of
      the choline acetyltransferase-immunoreactive neurons had fusiform, oval, or
      polygonal somata with somatic diameters greater than 20 microns and contained
      deeply invaginated nuclei surrounded by copious cytoplasm. In addition, choline
      acetyltransferase-immunoreactive neurons with somatic diameters between 10 and 20
      microns were also demonstrated. The grafts' substance P-like-immunoreactive
      neurons, which had somatic diameters between 10 and 25 microns and had oval or
      polygonal perikarya, could be classified into two types based on their
      ultrastructural characteristics. Type I neurons contained an unindented nucleus
      which was surrounded by a thin rim or moderate amount of cytoplasm, whereas Type
      II immunoreactive neurons contained an indented nucleus which was surrounded by
      copious cytoplasm. Choline acetyltransferase- and substance P-like-immunoreactive
      dendrites in the grafts' neuropil were contacted by multiple unlabeled axon
      terminals. In addition, choline acetyltransferase- and substance P-like
      immunoreactive axon terminals forming symmetric contacts with unlabeled dendrites
      were present within the graft. The study demonstrated that many of the
      neuroanatomical features of choline acetyltransferase- and substance P-like
      immunoreactive elements found in the normal rat striatum are present in mature
      fetal striatal grafts.

PMID- 1374857
TI  - Vasoconstrictor, vasodilator and pilomotor pathways in sympathetic ganglia of
      guinea-pigs.
AB  - Triple-labelling immunofluorescence and retrograde axonal tracing with
      fluorescent dyes have been combined to identify and characterize the neuropeptide
      content of vasoconstrictor, vasodilator and pilomotor neurons in the lumbar
      sympathetic ganglia of guinea-pigs. Postganglionic noradrenergic pilomotor
      neurons lacked immunoreactivity to neuropeptide Y and comprised up to about 30%
      of postganglionic neurons. Most post-ganglionic noradrenergic neurons that
      contained neuropeptide Y immunoreactivity were likely to be vasoconstrictor
      neurons, although some noradrenergic neurons containing neuropeptide Y projected
      to pelvic viscera. Vasoconstrictor neurons comprised up to about 60% of
      postganglionic neurons. About 15% of postganglionic neurons were non
      noradrenergic and contained immunoreactivity to vasoactive intestinal peptide,
      neuropeptide Y and dynorphin. They mostly innervated blood vessels supplying
      skeletal muscles and were likely to be vasodilator neurons. Endings of presumed
      preganglionic neurons containing immunoreactivity to substance P were exclusively
      associated with vasodilator neurons. Conversely, presumed preganglionic endings
      containing immunoreactivity to calcitonin gene-related peptide were exclusively
      associated with vasoconstrictor neurons, although not all vasoconstrictor neurons
      had such endings associated with them. Presumed preganglionic terminals
      containing immunoreactivity to enkephalin were associated with some
      postganglionic neurons in each functional class. These results show that
      preganglionic and postganglionic sympathetic neurons lying in different
      functional pathways can be distinguished by their neuropeptide content as well as
      their projections. The identification of neurochemically distinct functional
      pathways begins to explain how the sympathetic nervous system is organized to
      allow the precise control of discrete target tissues.

PMID- 1374858
TI  - Immunocytochemical evidence that GABA and neurotensin exist in different neurons
      in laminae II and III of rat spinal dorsal horn.
AB  - Pre-embedding immunocytochemistry with antiserum to neurotensin was combined with
      post-embedding immunocytochemistry with GABA antiserum, in order to identify
      neurotensin- and GABA-containing neurons in laminae I-III of rat spinal dorsal
      horn. The distribution of cell bodies containing these two compounds was similar
      to that which has been described previously. None of the 88 neurotensin
      immunoreactive neurons which were tested showed GABA-like immunoreactivity, which
      suggests that GABA and neurotensin exist in different cells in this region. Since
      both compounds are thought to be present in islet cells, it is likely that there
      are two neurochemically distinct populations of islet cells in lamina II of rat
      spinal cord.

PMID- 1374859
TI  - Whole-cell currents in two subpopulations of cultured rat petrosal neurons with
      different tetrodotoxin sensitivities.
AB  - In this study we use whole-cell recording to characterize at least two distinct
      populations of cultured neurons from perinatal rat petrosal or petrosal/jugular
      ganglia based on differential sensitivity of the transient inward Na+ current to
      tetrodotoxin. These ganglia supply chemoreceptor and baroreceptor afferents which
      mediate several cardiovascular reflexes. Approximately 50% of the neurons sampled
      had Na+ currents that were virtually unaffected by bath addition of tetrodotoxin
      (0.5-2.0 microM) but were abolished by choline substitution for external Na+. The
      majority of the remaining neurons had Na+ currents that were rapidly and
      reversibly blocked by 500 nM tetrodotoxin. A few cells had both tetrodotoxin
      resistant and tetrodotoxin-sensitive Na+ currents. All neurons had similar
      voltage-activated Ca2+ and K+ currents. The inward Ca2+ current had no obvious
      fast transient or T-type component and appeared to be due mainly to the presence
      of long-lasting L-type Ca2+ channels. The outward currents consisted largely of a
      delayed rectifying K+ current (IKdr) and a Ca(2+)-activated K+ current (IKca),
      but no obvious fast transient K+ current (IA) was observed. Exposure to a
      chemosensory stimulus, hypoxia (PO2 approximately 20 Torr), had no effect on
      these neurons, in contrast to the pronounced decrease in K+ current it produces
      in cultured glomus cells, the presumed chemoreceptors and normal targets for a
      subset of petrosal neurons in vivo. Current-clamp recordings indicated that some
      neurons gave single spikes while others gave multiple spikes in response to long
      depolarizing stimuli. No correlation between spiking behaviour and tetrodotoxin
      sensitivity was observed. Thus, cultures enriched in petrosal neurons contain
      subpopulations with differential sensitivities to tetrodotoxin. Since many of
      these neurons innervate a single chemosensory target organ, the carotid body, it
      is of interest to know whether one or both subtypes can form functional synapses
      with glomus cells of the carotid body and mediate a chemoreceptor reflex.

PMID- 1374860
TI  - Delayed treatment with nerve growth factor improves acquisition of a spatial task
      in rats with lesions of the nucleus basalis magnocellularis: evaluation of the
      involvement of different neurotransmitter systems.
AB  - Rats received bilateral lesions of the nucleus basalis magnocellularis by
      infusion of ibotenic acid. Fourteen days later, osmotic minipumps releasing human
      recombinant nerve growth factor (0.3 micrograms/day) were implanted
      subcutaneously. Starting one month after the lesion, spatial learning of the
      animals was tested using the Morris water maze. Acquisition of the task was
      impaired by the lesion, but treatment with nerve growth factor reduced the
      average latency to find the platform by approximately 9 s, which represents 28%
      of the lesion-induced behavioral deficit. Retention of this task and spatial
      acuity, tested in a trial in which the platform was not present, did not show a
      statistically significant improvement. Lesions of the nucleus basalis
      magnocellularis reduced the choline acetyltransferase activity in the neocortex,
      but not in the hippocampus. Treatment with nerve growth factor increased the
      choline acetyltransferase activity in the neocortex but not in the hippocampus.
      There was no significant difference in the levels of norepinephrine, dopamine,
      serotonin or their metabolites in the cortex or hippocampus between nerve growth
      factor-treated animals and lesioned control animals. There was no significant
      correlation between any of these neurochemical changes and behavioral performance
      (acquisition and spatial acuity). Treatment with nerve growth factor did not
      increase the number or the size of nerve growth factor receptor-immunoreactive
      neurons in the nucleus basalis magnocellularis. These data suggest that delayed
      treatment with nerve growth factor results in an improvement of spatial learning
      in rats with lesions of the nucleus basalis magnocellularis. A possible role for
      cholinergic mechanisms in this effect is discussed.

PMID- 1374861
TI  - Ultrastructural evidence for neurogenically mediated changes in blood vessels of
      the rat dura mater and tongue following antidromic trigeminal stimulation.
AB  - We investigated the effects of unilateral electrical trigeminal ganglion
      stimulation (0.1 or 1.0 mA, 5 Hz, 5 ms, 5 min) on the morphology of blood vessels
      within the rat dura mater and tongue using light and transmission electron
      microscopy. Stimulation at both intensities caused changes which were confined to
      the ipsilateral post-capillary venules except in the tongue where arterioles were
      affected as well. Changes were more marked after 1.0 mA. Dramatic increases in
      the numbers of endothelial pinocytotic vesicles were found along the luminal and
      abluminal surfaces ipsilateral to the stimulation. Tight junctions remained
      largely intact, except that injected ferritin particles were occasionally trapped
      inside these junctions. Cytoplasmic microvilli and endothelial blebs were
      sometimes present as well. Approximately 80% of the examined dural post-capillary
      venules showed one or more of these endothelial changes. Horseradish peroxidase
      injected intravenously 5 min prior to stimulation was detected in the
      extracellular space surrounding dural blood vessels and within pinocytotic
      vesicles. Ferritin injected similarly, was also localized in post-capillary
      venule walls, interstitial spaces, intraendothelial vesicles and in vacuoles.
      Platelet accumulation and aggregation were present in approximately 10% of post
      capillary venules in dura and tongue. These changes were associated with mast
      cell secretion, but neither vascular nor mast cell activation was observed in
      adult rats in whom C-fibers were destroyed during the neonatal period with
      capsaicin. The present observations provide morphological evidence which supports
      findings from previously reported albumin tracer studies suggesting enhanced
      transport and endothelial activation following electrical stimulation of small
      caliber afferent fibers.

PMID- 1374862
TI  - Morphology and electrophysiology of superior laryngeal nerve afferents and
      postsynaptic neurons in the medulla oblongata of the cat.
AB  - Intra-axonal recordings were made from 24 afferent fibres of the superior
      laryngeal nerve in and around the nucleus tractus solitarius, in 26
      pentobarbitone-anaesthetized cats. Conduction velocity ranged from 15 to 38 m/s.
      Four afferents were injected with horseradish peroxidase. They showed dense
      terminal arborization in the region of the ventral and ventrolateral subnuclei of
      the nucleus tractus solitarius, both rostral and caudal to the obex. Six other
      intra-axonal recordings were thought to originate from axons of neurons
      postsynaptic to superior laryngeal afferents; one of these was injected with
      horseradish peroxidase and showed a similar arborization pattern to that of the
      afferent axons. In the same region, intracellular recordings were made from 124
      neurons which responded to superior laryngeal nerve stimulation with excitatory
      postsynaptic potentials (mean latency 2.7 +/- 1.0 ms). Ninety-nine of these
      neurons were thought to receive a monosynaptic input. The stimulation threshold
      evoking these responses was similar to that which inhibited phrenic nerve
      discharge. Eleven of the monosynaptically excited neurons were injected with
      horseradish peroxidase. They had fusiform or stellate somata and simple dendritic
      trees, radiating mainly in the transverse plane. In one experiment, in which both
      a superior laryngeal nerve afferent fibre and a neuron were labelled, afferent
      terminal varicosities were found in close apposition with the postsynaptic
      membrane of the injected neuron. Four of 14 (29%) tested neurons could be
      antidromically activated from the C3 spinal segment. The stimulus thresholds and
      onset latencies of the responses of superior laryngeal nerve afferents and
      medullary neurons to stimulation of the superior laryngeal nerve are consistent
      with their involvement in the reflex inhibition of respiratory neurons evoked by
      superior laryngeal nerve stimulation.

PMID- 1374863
TI  - Histochemistry of NADPH-diaphorase, a marker for neuronal nitric oxide synthase,
      in the peripheral autonomic nervous system of the mouse.
AB  - In order to identify possible sites of synthesis of nitric oxide in the
      peripheral nervous system, several mouse organs were investigated for the
      presence of NADPH-diaphorase activity. Diaphorase-positive neurons and fibers
      were localized in the tongue, submandibular salivary glands, gastrointestinal and
      biliary duct systems, lower urinary tract and pelvic ganglia. By thionin
      counterstaining it was found that a distinct subpopulation of neurons was
      labeled. The present study indicates that nitric oxide synthase may be present in
      intrinsic neurons of various organs, suggesting a widespread function of nitric
      oxide in the peripheral autonomic nervous system.

PMID- 1374864
TI  - [Interferon, VIN and HPV. Therapeutic prospectives].

PMID- 1374865
TI  - Dextran antibodies, complement conversion and circulating immune complexes after
      intravenous iron dextran therapy in dialysed patients.
AB  - Serum immune complexes, plasma dextran antibodies and percentage conversion of
      complement have been measured in 20 dialysed patients before and after an
      intravenous infusion of iron dextran providing 600 mg elemental iron. Complement
      conversion was unmeasurable and there were no changes in circulating immune
      complexes. The presence of dextran antibodies in nine patients before the
      infusion was not related to prior exposure to iron dextran. They became
      undetectable in these patients within hours after the infusion, reappearing 1
      month later in three. Two of three patients reporting mild aches and shivers on
      the day following the infusion had no detectable dextran antibodies. An adverse
      reaction involving inflamed joints occurred 1-2 days after a second infusion
      given to one of the patients studied above. The parameters under study were again
      measured and did not appear to relate to the reaction. The presence of dextran
      antibodies does not preclude the giving of iron dextran to patients on dialysis,
      and the immune complex and complement systems remain undisturbed by iron dextran
      infusions.

PMID- 1374866
TI  - Substance P variations in the hypothalamus of golden hamsters at different stages
      of the estrous cycle.
AB  - The changes in substance P concentrations in the hypothalamus of female golden
      hamsters were studied at the different stages of the estrous cycle. Substance P
      levels in the hypothalamus of hamsters were highest during estrus and lowest
      during diestrus I and proestrus. The concentrations of substance P during
      diestrus II were not significantly different from those observed during estrus.
      These results show that substance P levels in the hypothalamus of female hamsters
      undergo significant changes during the estrous cycle.

PMID- 1374867
TI  - Long-term survival of autologous muscle grafts in rat brain.
AB  - The ability of muscle to persist in the brain was explored. Pieces of rat
      quadriceps muscles were removed, minced and transplanted back into the same
      animal's cortex. Brains implanted with minced muscle consistently contained
      substantial grafts for at least 6 months. Histological, immunohistochemical, and
      electron microscopic examination indicated that the muscle grafts after 6 months
      contained healthy and well-differentiated myofibers. The long-term survival of
      muscle cells suggested that this technique will be useful for studies of brain
      and muscle and for the development of new therapeutic modalities.

PMID- 1374868
TI  - Selectivity of cholecystokinin (CCK) receptor antagonists, MK-329 and L-365,260,
      for axonally-transported CCK binding sites on the rat vagus nerve.
AB  - The ability of the cholecystokinin (CCK) receptor antagonists, MK-329 and L
      365,260, to selectively inhibit 125I-Bolton-Hunter-CCK8 binding to ligated rat
      vagus nerve in vitro was examined at concentrations ranging from 10(-10) M to 10(
      6) M. Both antagonists inhibited binding to CCK binding sites accumulating
      proximal to ligatures on the cervical vagus. Incubation of nerve sections in the
      presence of both antagonists produced an additive effect, indicating that both
      CCK-A and CCK-B binding sites are transported towards the periphery. In contrast,
      CCK binding sites accumulating distal to the ligature possessed the
      pharmacological characteristics of the CCK-B receptor sub-type only.

PMID- 1374869
TI  - Depletion of substance P and calcitonin gene-related peptide in sciatic nerve of
      rats with experimental diabetes; effects of insulin and aldose reductase
      inhibition.
AB  - This study was designed to determine whether deficient substance P in the sciatic
      nerve of diabetic rats was associated with a similar reduction in calcitonin gene
      related peptide and whether the depletion of either or both peptides could be
      affected by insulin treatment or by aldose reductase inhibition. Substance P and
      calcitonin gene-related peptide were measured as immunoreactivities in the same
      nerve extracts. The sciatic nerve content of substance P was significantly
      reduced in diabetic rats (0.063 +/- 0.011; all data are mean +/- 1 standard
      deviation in ng peptide/mg nerve protein; n = 9 for all groups) compared to
      controls (0.093 +/- 0.026). The calcitonin gene related peptide content was
      similarly reduced (2.14 +/- 0.49) compared to controls (3.78 +/- 1.21). Tight
      glycaemic control with insulin prevented completely the deficit in both peptides
      (substance P = 0.096 +/- 0.021, calcitonin gene-related peptide = 4.66 +/- 0.92).
      Treatment with the aldose reductase inhibitor, imirestat, corrected the substance
      P deficit (0.08 +/- 0.018) and attenuated the calcitonin gene-related peptide
      (3.55 +/- 1.03) depletion seen in the untreated diabetic animals. This indicates
      that the polyol pathway may play a role in the peptide status of the sciatic
      nerve. Regression analysis of all data gave r2 = 0.53, indicating a comparable
      effect of diabetes and the treatments on both peptides.

PMID- 1374870
TI  - Increase in substance P and CGRP, but not somatostatin content of innervating
      dorsal root ganglia in adjuvant monoarthritis in the rat.
AB  - Neuropeptides, synthesized in dorsal root ganglia (DRG), are implicated in
      nociception and neurogenic inflammation. Alterations in DRG neuropeptide levels
      have been described in polyarthritic rats, but these models are associated with
      widespread systemic disease. Using mild adjuvant-mediated monoarthritis of the
      left carpal joint we found significant increases in substance P (+69%) and
      calcitonin gene-related peptide (CGRP; +204+), but not somatostatin in
      ipsilateral C6/7 DRG. Peptide levels in contralateral DRG and other ipsilateral
      DRG were unaltered. Substance P and CGRP in DRG may be of importance in the
      pathogenesis and maintenance of adjuvant arthritis.

PMID- 1374871
TI  - An autoradiographic study of cortical projections from motor thalamic nuclei in
      the macaque monkey.
AB  - The special areal and laminar distributions of cortical afferent connections from
      various thalamic nuclei in the monkey (Macaca fuscata) were studied by using the
      anterograde axonal transport technique of autoradiography. The following findings
      were obtained. The superficial thalamocortical (T-C) projections, terminating in
      the (superficial half of) cortical layer I, arise mainly from the nucleus
      ventralis anterior, pars principalis (VApc) and nucleus ventralis lateralis, pars
      oralis (VLo), and possibly from the nucleus ventralis lateralis, pars medialis
      (VLm) and nucleus ventralis anterior, pars magnocellularis (VAmc). The VApc gives
      rise to the superficial T-C and deep T-C projections onto the postarcuate
      premotor area around the arcuate genu and spur, and onto the dorsomedial part of
      the caudal premotor area as well as the supplementary motor area (SMA). The VApc
      also gives rise to only deep T-C projections onto the remaining premotor area and
      onto the rostral bank of the arcuate sulcus as well as the ventral bank of the
      cingulate sulcus at the level of the premotor area. The VLo gives rise to the
      superficial T-C projections onto the ventrolateral part of the motor area (mainly
      to the forelimb motor area) and onto the dorsomedial part to the mesial cortex at
      the rostral level of the motor area. The VAmc gives rise to the superficial T-C
      projections onto the banks of the arcuate genu and adjacent region of area 8.
      Area X, the nucleus ventralis posterolateralis, pars oralis (VPLo), nucleus
      ventralis posterolateralis, pars caudalis (VPLc), nucleus ventralis
      posteromedialis (VPM) and possibly the nucleus ventralis lateralis, pars caudalis
      (VLc) send only deep T-C projections. The dorsal and medial parts of the VLc
      project onto the premotor area, the rostral part of the motor area and the SMA,
      and also the ventral bank of the cingulate sulcus. Area X projects onto the
      premotor area, the SMA, and the caudal part of area 8. The thalamic relay nuclei
      projecting onto the frontal association cortex were found to be the VAmc, medial
      VLc and area X.

PMID- 1374872
TI  - Organization of the pontine nuclei.
AB  - The pontine nuclei provide the cerebellar hemispheres with the majority of their
      mossy fiber afferents, and receive their main input from the cerebral cortex.
      Even though the vast majority of pontine neurons send their axons to the
      cerebellar cortex, and are contacted monosynaptically by (glutamatergic)
      corticopontine fibers, the information-processing taking place is not well
      understood. In addition to typical projection neurons, the pontine nuclei contain
      putative GABA-ergic interneurons and complex synaptic arrangements. The
      corticopontine projection is characterized by a precise but highly divergent
      terminal pattern. Large and functionally diverse parts of the cerebral cortex
      contribute; in the monkey the most notable exception is the almost total lack of
      projections from large parts of the prefrontal and temporal cortices. Within
      corticopontine projections from visual and somatosensory areas there is a de
      emphasis of central vision and distal parts of the extremities as compared with
      other connections of these sensory areas. Subcorticopontine projections provide
      only a few percent of the total input to the pontine nuclei. Certain cell groups,
      such as the reticular formation, project in a diffuse manner whereas other
      nuclei, such as the mammillary nucleus, project to restricted pontine regions
      only, partially converging with functionally related corticopontine connections.
      The pontocerebellar projection is characterized by a highly convergent pattern,
      even though there is also marked divergence. Neurons projecting to a single
      cerebellar folium appear to be confined to a lamella-shaped volume in the pontine
      nuclei. The organization of the pontine nuclei suggests that they ensure that
      information from various, functionally diverse, parts of the cerebral cortex and
      subcortical nuclei are brought together and integrated in the cerebellar cortex.

PMID- 1374873
TI  - Metaphor in nursing theory.

PMID- 1374874
TI  - Adult extrarenal rhabdoid tumor of the lacrimal gland.
AB  - A 50-year-old man presented with a rapidly growing mass in the area of the right
      lacrimal gland. An initial erroneous histopathologic diagnosis of a pleomorphic
      adenoma made on a small-incisional biopsy was later corrected to a malignant
      rhabdoid tumor when a wide local excision of the tumor was performed. The tumor
      was composed predominantly of dyscohesive, globoid, and eosinophilic cells, which
      frequently contained cytoplasmic inclusions. These were demonstrated to be
      composed of whorls of intermediate vimentin filaments. The tumor cells expressed
      epithelial membrane antigen as well as cytokeratin. Ultrastructurally, they
      displayed intercellular junctions and interrupted segments of linear basement
      membrane material. These findings, together with the development of the lesion
      within the parenchyma of the lacrimal gland, are suggestive of an epithelial
      origin. The patient was treated with radical surgery and adjunctive radiotherapy
      and chemotherapy, which are the recommended treatment modalities for this highly
      malignant tumor.

PMID- 1374875
TI  - Comparison of fluorescein and rose bengal staining.
AB  - The authors have recently reported that rose bengal is not a vital dye, and
      stains whenever the cultured cells are not covered by such components as albumin
      and mucin, and such a tear substitute as carboxycellulose. In this report, using
      cultured cells as well as normal rabbit corneas, they characterize and correlate
      the staining differences between rose bengal and fluorescein with the differences
      in their chemical structures. Fluorescein differs from rose bengal in its lack of
      intrinsic toxicity, photodynamic action, and ability to be blocked by the above
      mentioned substances. Fluorescein staining is increased by rapid stromal
      diffusion and hence can manifest whenever there is disruption of cell-cell
      junctions. In contrast, rose bengal staining ensues whenever there is deficiency
      of preocular tear film protection. These experimental data may help interpret the
      clinical staining properties of these two dyes and enhance the understanding of
      the pathogenesis of various ocular surface disorders.

PMID- 1374876
TI  - Studies on the regranulation of salivary gland serous cells. An electron
      microscopical study in the rat.
AB  - The degranulation and regranulation process was investigated after alpha
      adrenergic stimulation on the rat submandibular gland. The submandibular gland in
      rat contains both serous and mucous cells. It has earlier been shown that serous
      cells filled with heavy-metal granules, are markedly more radiosensitive than
      cells without granules. In experiments with emptying the serous cell of their
      content of granules by administering an alpha-adrenergic stimulant,
      cyclocytidine, there has been found a decrease in irradiation damage in salivary
      gland tissue after irradiation. Injection of cyclocytidine, 150 mg/kg, was given
      i.p. to the rat. After 1 h there was almost complete depletion of granules in the
      serous cells, no morphological aberration was seen in the mucous cells. This
      effect still remained after 6 h. A beginning of regranulation with apical
      granules was seen 12 h after injection. After 24 h an almost complete
      regranulation had occurred in the salivary gland serous cells. The mucous cells
      did not show any morphological aberration. Our intent is to reduce unwanted
      salivary gland damage in patients with head and neck cancer when treated with
      radiotherapy. Depletion of heavy-metal granules in serous cells, before
      irradiation may diminish morphological destruction in the salivary glands. As a
      nearly total degranulation is present between 1-6 h after stimulation, this
      should be the optimal time for radiotherapy.

PMID- 1374877
TI  - Myths of risk stratification.

PMID- 1374878
TI  - Implantation of a cardioverter/defibrillator in the subpectoral region combined
      with a nonthoracotomy lead system.
AB  - An implantable cardioverter defibrillator was placed into a subpectoral pocket
      via the incision for cephalic venotomy during implantation of a nonthoracotomy
      lead system. The approach obviated another incision and subcutaneous tunneling of
      the leads. There were no perioperative complications and after 6 months of follow
      up, the patient continues to tolerate the device satisfactorily.

PMID- 1374879
TI  - Seven years of left ventricular pacing due to malposition of pacing electrode.
AB  - The case report is presented of a patient in whom an uncomplicated left
      ventricular transvenous pacing produced right bundle branch block (RBBB). A
      diagnostic echocardiography, confirmed by cine cardiovascular computed
      tomography, showed that there was no rupture of the right ventricle and diagnosed
      a left ventricular pacing, due to malposition of the pacing electrode. The
      patient was treated with aspirin and dipyridamole during the last 6 years of
      follow-up, without any complications, including 1 year of pacing, prior to
      admission.

PMID- 1374880
TI  - Proarrhythmic effects of reactive hypoglycemia.
AB  - A patient with refractory atrioventricular nodal reentry tachycardia is reported
      in whom it was possible to document that reactive hypoglycemia was the trigger
      for aggravation of arrhythmia. Over a period of 6 years, a series of
      electrophysiological studies revealed that, when the patient was in a
      hypoglycemic state, initiation of tachycardia was easy and most importantly that
      tachycardla termination by extra-stimulus pacing always failed. Furthermore,
      atrial fibrillation was inducible or spontaneously occurred only when the blood
      glucose level was reduced by IV insulin administration.

PMID- 1374881
TI  - Inverted pacemaker mediated tachycardia induced during noninvasive
      electrophysiology testing.
AB  - This report describes a case in which an implanted pacemaker programmed to
      perform noninvasive electrophysiology testing resulted in an unusual form of
      pacemaker mediated tachycardia. The method of chest wall stimulation was used by
      programming a unipolar, triggered pacing mode with a short refractory period. In
      the AAT mode, far-field R wave sensing occurred beyond the physiological atrial
      refractory period. The triggered atrial response resulted in a single chamber,
      pacemaker mediated tachycardia.

PMID- 1374882
TI  - Propafenone associated agranulocytosis.
AB  - Propafenone hydrochloride was approved for marketing by the United States (U.S.)
      Food and Drug Administration (FDA) in November 1989. During U.S. clinical trials
      of propafenone, one case of agranulocytosis was seen. Seven additional cases have
      been reported outside the U.S. One German report of profound but reversible
      granulocytopenia appeared in 1982. In January 1991, the FDA reviewed adverse
      events reported with propafenone. Four reports of agranulocytosis were identified
      and are described. The reporting rate of approximately one case of
      agranulocytosis per 10,000 propafenone prescriptions per year likely
      underestimates the true incidence of this adverse event.

PMID- 1374883
TI  - Hemodynamic effects of different temporary pacing modes for the management of
      bradycardias complicating acute myocardial infarction.
AB  - Twelve patients requiring temporary pacing following acute myocardial infarction
      (AMI) (10 heart block, 2 junctional bradycardia) had hemodynamic measurements
      taken with ventricular demand pacing at 80 ppm (VVI80), ventricular demand pacing
      at the atrial rate (VVIa), physiological pacing (DDD), and spontaneous
      (intrinsic) rhythm. VVI80 mode did not improve any hemodynamic parameter compared
      with spontaneous rhythm. VVIa mode improved diastolic and mean arterial pressures
      only. DDD mode improved most hemodynamic parameters compared with spontaneous
      rhythm (cardiac output by 29% [P less than 0.0001]; blood pressure: diastolic by
      24% [P less than 0.01], systolic by 19% [P less than 0.01], mean by 21% [P less
      than 0.005]; pulmonary wedge pressure by 10% [P = 0.057] and right atrial
      pressure by 24% [P less than 0.005]) and also significantly improved some
      parameters compared with VVIa (cardiac output by 20% [P less than 0.001],
      systolic blood pressure by 11% [P less than 0.01] and right atrial pressure by
      15% [P less than 0.01]). Physiological pacing is hemodynamically superior both to
      ventricular pacing and spontaneous rhythm for patients requiring temporary pacing
      following AMI. Ventricular pacing at 80 ppm has little hemodynamic advantage over
      spontaneous rhythm.

PMID- 1374884
TI  - Atrial natriuretic factor release during exercise in patients successively paced
      in DDD and rate matched ventricular pacing.
AB  - Dual chamber pacemakers were implanted in nine patients with permanent second or
      third degree AV block (eight had complete retrograde block). Two identical
      exercise tests were performed after at least 1 month after implantation. During
      the first test (T1) the pacemaker was programmed to the DDD mode and heart rates
      were recorded every 15 to 30 seconds during exercise and 30 minutes after
      exercise. Following 30 minutes of rest, the implanted pacemaker was programmed to
      the VVT mode and driven by an external pacemaker via a skin electrode. The second
      exercise test (T2) was then performed and the rate of the external pacemaker was
      progressively changed to reproduce exactly the rate observed during T1 at the
      same exercise stress. Atrial natriuretic factor (ANF) levels were determined at
      rest, at regular intervals during exercise, and 30 minutes after exercise. ANF
      levels and release were statistically higher during rate matched ventricular,
      than DDD pacing. It is concluded that preservation of AV synchrony reduces ANF
      release induced by heart rate acceleration during exercise.

PMID- 1374885
TI  - Quantitative relationship between atrial refractoriness and the dispersion of
      refractoriness in atrial vulnerability.
AB  - We investigated the quantitative relationship between the atrial refractory
      period and the dispersion of refractoriness with respect to atrial vulnerability
      in 19 adult mongrel dogs. The atrial effective refractory period (AERP) was
      measured at the sinus node area (SNA), the low posterior right atrium (LRA), and
      the distal coronary sinus. The study was performed under the following
      conditions: (1) control status; (2) hypothermia (30 degrees C); (3) vagus nerve
      stimulation; and (4) a combination of (2) and (3). The subjects were separated
      into two groups: atrial fibrillation (AF) (+) group (n = 23), which developed AF
      by atrial extrastimulus due to increased vulnerability, and AF (-) group (n =
      39), which did not develop AF. The mean AERP was 97 +/- 21 msec (mean +/- SD) in
      the AF (+) group and 124 +/- 23 msec in the AF (-) group, with a significantly
      shorter refractory period seen in the former (P less than 0.001). The dispersion
      of refractoriness was 59 +/- 24 msec in the AF (+) group and 29 +/- 18 msec in
      the AF (-) group, with a significant increase noted in the former (P less than
      0.001). On X-Y coordinates (where X denotes the AERP, and Y denotes the
      dispersion of refractoriness) the data from the AF (+) group were clustered in
      the upper left region of the graph while the data from the AF (-) group were
      clustered in the lower right region. These two groups were separated by a linear
      equation of Y = 0.86X - 57 with a predictability of 90.3%.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1374886
TI  - Catheter ablation of ventricular tachycardia: role of the underlying etiology and
      the site of energy delivery.
AB  - The role of DC catheter ablation (CA) to treat patients with sustained
      monomorphic ventricular tachycardia (VT) is still debated. To assess the efficacy
      of VT CA, we studied the follow-up of 49 patients with VT who underwent CA. There
      were 33 patients with an old myocardial infarction (MI) (group G I) and 16
      patients had noncoronary VT (group G II): CA was performed at the earliest
      endocardial activation (EEA) (20 patients in G I, 14 patients in G II) or at the
      area of slow conduction (ASC) (13 patients in G I, 2 patients in G II). During
      the mean follow-up of 35 +/- 25 (1-79) months, there were 17 patients in G I
      (52%) and 12 patients in G II (75%) with VT recurrences (P less than 0.05).
      Recurrences of VT was observed in 4 of 15 patients (27%) when CA was performed at
      the ASC, compared to 25 of 34 patients (74%) with CA at the EEA (P less than
      0.01). These data show that DC CA is more successful in patients with coronary
      artery disease, particularly when CA is performed at the ASC.

PMID- 1374888
TI  - Programmed electrical stimulation of the ventricle: an efficient, sensitive, and
      specific protocol.
AB  - A relatively simple and efficient ventricular programmed electrical stimulation
      (PES) protocol was developed, capable of achieving high degrees of sensitivity
      and specificity. In a series of 481 subjects, 1, 2, and 3 extrastimuli (ES) were
      used successively during sinus rhythm and ventricular pacing at two drive cycle
      lengths, at one or more ventricular sites, together with rapid ventricular
      pacing, and other maneuvers such as isoproterenol infusion. Three ES were used
      immediately after two ES at each drive rate, rather than returning after
      completion of the protocol with two ES. Using the protocol, appropriate
      arrhythmias could be induced in 88% of all patients with ventricular
      fibrillation, 84% of all patients with sustained ventricular tachycardia (91%
      with underlying coronary disease), and 58% of patients with severe nonsustained
      ventricular tachycardia. There were significant differences in inducibility
      between patients whose ventricular arrhythmias were due to coronary artery
      disease and other causes. In contrast, sustained ventricular arrhythmias (all
      ventricular fibrillation) could be induced in only 5% of a control group of
      control patients, for a specificity of 95%. The protocol described is simpler and
      more efficient than those that use exhaustive testing of two ES before going to
      three ES. Three ES during sinus rhythm proved to be the most productive step,
      with a higher yield ratio (true: false-positives) than two ES or three ES during
      pacing, especially at faster rates. Greater efficiency is also achieved by
      leaving the timing of an extrastimulus just beyond its effective refractory
      period when an additional extrastimulus is to be added, compared to protocols in
      which the extrastimulus is moved later in the cycle and then decremented in
      tandem with the additional extrastimulus. Coupling intervals less than 200 msec
      produced some false-positives, but fewer overall than intervals greater than or
      equal to 200 msec, and with yield ratios comparable to other protocol steps. The
      protocol described meets NASPE standards for ventricular programmed stimulation
      protocols, and with its demonstrated specificity and relative simplicity and
      efficiency may be useful as a model for groups not yet committed to an
      alternative protocol.

PMID- 1374887
TI  - Is DDD pacing superior to VVI,R? A study on cardiac sympathetic nerve activity
      and myocardial oxygen consumption at rest and during exercise.
AB  - Rate responsive ventricular pacing (VVI,R) has been demonstrated to equal atrial
      synchronous ventricular pacing (DDD) with regard to hemodynamics and exercise
      tolerance. Whether the two modes are also comparable, with regard to cardiac
      metabolic effects, is not yet clear. We assessed central hemodynamics, cardiac
      sympathetic nerve activity (cardiac norepinephrine overflow), and myocardial
      oxygen consumption in 16 patients treated with rate responsive atrial synchronous
      ventricular pacemakers (DDD,R) due to high degree AV block. The study was
      performed at rest and during supine exercise at two workloads (30 +/- 12 and 68
      +/- 24 watts, respectively) during VDD and rate matched VVI pacing (VVIm).
      Ventricular rates at rest and during both workloads were almost identical.
      Cardiac output at rest tended to be higher in the VDD mode, due to a slightly
      higher stroke volume. Central pressures including right atrial pressure and
      pulmonary capillary wedge pressure were similar in the pacing modes. The coronary
      sinus blood flow, the coronary sinus arteriovenous oxygen difference, and the
      myocardial oxygen consumption did not differ between the two pacing modes.
      Cardiac norepinephrine overflow was similar in the two pacing modes, at rest or
      during exercise. Thus, we found no significant differences between VDD and VVIm
      pacing with regard to central hemodynamics, cardiac sympathetic nerve activity
      (cardiac norepinephrine overflow), or myocardial oxygen consumption either at
      rest or during moderate exercise.

PMID- 1374890
TI  - Clinical application of external pacing: a renaissance?

PMID- 1374889
TI  - Sudden death in patients with congestive heart failure: future directions.
AB  - Sudden, unexpected cardiac death continues to be a major clinical problem in
      patients with congestive heat failure. This review summarizes the current state
      of knowledge regarding the identification and management of these patients. The
      roles of ambulatory ECG monitoring, electrophysiological testing, signal-averaged
      ECG, and other methods of predicting increased risk of sudden death are
      discussed. The modes of sudden cardiac death and the potential mechanisms of
      ventricular arrhythmias in congestive heart failure are reviewed. Current
      therapeutic options including antiarrhythmic drugs, neurohormonal blockade, and
      automatic implantable cardioverter defibrillators are discussed. Finally, future
      directions and ongoing clinical investigations of the management of these complex
      patients are considered.

PMID- 1374891
TI  - Performance of implantable cardiac rhythm management devices.

PMID- 1374892
TI  - Ontogeny of the secretory immune system: maturation of a functional polymeric
      immunoglobulin receptor regulated by gene expression.
AB  - In the rat, secretion of polymeric IgA from serum into bile is dependent upon the
      presence of a functional polymeric immunoglobulin receptor (pIgR) that acts as a
      hepatocyte plasma membrane receptor for ligand binding and as a transcellular
      transport molecule. The objective of this study was to document the developmental
      maturation and regulation of functionally intact rat liver pIgR. An adult pattern
      of IgA secretion was not detected until after day 23 postpartum (dPP), by using
      intravenously injected 125I-labeled dimeric IgA. Radioactive dimeric IgA was not
      detectable in hepatocyte transport vesicles until 21 dPP by electron microscopy
      autoradiographic analysis. By using a rabbit polyclonal antibody against the rat
      secretory component domain of the pIgR, Western blot analysis demonstrated that
      the plasma-membrane-bound pIgR levels in hepatocytes from rats aged 19-22 dPP
      increased 10-fold during this period. To determine whether or not this increase
      in membrane-bound pIgR reflected increased pIgR gene expression, we probed
      Northern blots of total cellular RNA extracted from neonatal rat liver with pIgR
      cDNA [GORF-1; Banting, G., Brake, B., Braghetta, P., Luzio, J.P. & Stanley, K. K.
      (1989) FEBS Lett. 254, 177-183]. The pIgR RNA levels between 19 and 22 dPP rose
      more than 20-fold and paralleled the increased membrane-bound pIgR protein during
      this same interval. These data demonstrate a developmentally regulated process
      that controls the ontogeny of biliary dimeric IgA secretion at the termination of
      the third week postpartum. The process appears to depend on the up-regulation of
      pIgR gene expression.

PMID- 1374893
TI  - Three additional inositol 1,4,5-trisphosphate receptors: molecular cloning and
      differential localization in brain and peripheral tissues.
AB  - Three inositol 1,4,5-trisphosphate receptor (IP3R) cDNAs, designated IP3R-II, 
      III, and -IV, were cloned from a mouse placenta cDNA library. All three display
      strong homology in membrane-spanning domains M7 and M8 to the originally cloned
      cerebellar IP3R-I, with divergences predominantly in cytoplasmic domains. Levels
      of mRNA for the three additional IP3Rs in general are substantially lower than
      for IP3R-I, though in the gastrointestinal tract the levels of IP3R-III may be
      comparable to IP3R-I. Cerebellar Purkinje cells express at least two and possibly
      three distinct IP3Rs, suggesting heterogeneity of IP3 action within a single
      cell.

PMID- 1374894
TI  - Differential expression of c-fos and zif268 in rat striatum after haloperidol,
      clozapine, and amphetamine.
AB  - Antipsychotic drugs are monoamine receptor antagonists. However, the mechanisms
      by which these direct actions are translated into therapeutic effects are
      unknown. Candidate mechanisms include receptor-mediated regulation of gene
      expression in target neurons. Inducible transcription factors, including certain
      immediate early genes (IEGs), may mediate between receptor-activated second
      messenger systems and expression of genes involved in the differentiated
      functions of neurons. We examined the specificity of induction of the IEGs c-fos
      and zif268 after acute administration of several antipsychotic drugs and, for
      comparison, the stimulant amphetamine, which has pharmacologic effects relatively
      opposite to those of antipsychotics. Antipsychotic drugs with potent dopamine D2
      receptor antagonist properties, such as haloperidol, induced both c-fos and
      zif268 mRNA in the caudate-putamen; however, the atypical antipsychotic drug
      clozapine induced zif268 but not c-fos mRNA in that region. Similarly,
      haloperidol, but not clozapine, induced c-Fos-like immunoreactivity in the
      caudate-putamen. In contrast, both drugs induced c-Fos-like immunoreactivity in
      the nucleus accumbens. Like haloperidol, amphetamine induced both c-fos and
      zif268 mRNA in the caudate-putamen, but the anatomic patterns of induction of c
      Fos-like immunoreactivity by the two drugs were dramatically different.
      Haloperidol and amphetamine induced AP-1 binding activity in cell extracts from
      the caudate-putamen, indicating that drug-induced IEG expression results in
      protein products that may function in the regulation of target gene expression.
      Thus these data demonstrate that inductions of IEG expression by haloperidol,
      clozapine, and amphetamine are specific, may be biologically relevant, and
      suggest avenues for further investigation.

PMID- 1374895
TI  - Design of a long-acting follitropin agonist by fusing the C-terminal sequence of
      the chorionic gonadotropin beta subunit to the follitropin beta subunit.
AB  - Follitropin (FSH) is a pituitary glycoprotein hormone that is essential for the
      development of ovarian follicles and testicular seminiferous tubules. FSH is used
      clinically to stimulate follicular maturation for in vitro fertilization and
      treatment of anovulatory women. One issue regarding the clinical use of FSH is
      its short half-life in the circulation. To address this point, we constructed
      chimeric genes containing the sequence encoding the C-terminal peptide of the
      chorionic gonadotropin beta subunit (CG beta) fused to the translated sequence of
      the human FSH beta subunit (FSH beta). This region of CG beta is important for
      maintaining the prolonged plasma half-life of human CG dimer. The presence of the
      C-terminal peptide sequence did not significantly affect assembly of FSH beta
      with the alpha subunit or secretion of the dimer. In vitro receptor binding and
      steroidogenic activity of dimer bearing the FSH beta-C-terminal peptide chimera
      were the same as wild-type FSH. However, both the in vivo potency and half-life
      in circulation of the dimer bearing either one or two C-terminal peptide units
      were enhanced. Dimers containing FSH beta-CG beta chimeras could serve as potent
      FSH agonists for clinical use, and the present strategy may have wide
      applications for enhancing the in vivo half-life of diverse proteins.

PMID- 1374897
TI  - A 33-kDa polypeptide with homology to the laminin receptor: component of
      translation machinery.
AB  - A 33-kDa polypeptide (termed p40), which shares an antigenic determinant with a
      laminin receptor and is under translational control, is believed to serve as a
      precursor to the receptor and to be related to the neoplastic state. The present
      study of subcellular localization of this protein shows it to be a cytoplasmic
      component not associated with the plasma membrane. Most of the cellular p40 was
      found to be associated with polyribosomes as well as with 40S to 60S cytoplasmic
      particles. Conditions that lead to polysome disruption also caused release of the
      polysomal form of p40 as smaller particles, and polysome reconstitution was
      accompanied by uptake of p40 into these structures. Because of the large
      abundance of this protein in the cells (six to eight copies per ribosome), it is
      unlikely that it represents a factor that associates with the 40S preinitiation
      complex. The p40-containing particles appear to represent a newly discovered
      structure involved in the process of polysome formation.

PMID- 1374896
TI  - Two mutations in the beta-globin polyadenylylation signal reveal extended
      transcripts and new RNA polyadenylylation sites.
AB  - Two mutations in the beta-globin poly(A) signal were identified in Israeli
      patients with beta +-thalassemia by sequence analysis following PCR. One is a
      point mutation (AATAAA----AATAAG) and the other is a 5-base-pair deletion (AATAAA
      ---A----). The mutant genes were used to investigate the function of the poly(A)
      signal in vivo and to evaluate the mechanism whereby these mutations lead to a
      thalassemic phenotype. Analysis of RNA derived from peripheral blood demonstrated
      the presence of elongated RNA species in patients carrying either mutation. Other
      aspects of RNA processing (initiation, splicing) were unimpaired. RNA obtained
      from the patients carrying the point mutation contained four discrete, extended
      RNA species, 1500-2900 nucleotides long, which were found to be polyadenylated.
      Some normal cleavage-polyadenylylation was also observed. The 5-base-pair
      deletion completely abolished cleavage at the normal site. This deletion mutation
      resulted in a phenotype of beta +-thalassemia, thus providing evidence that the
      extended mRNAs are translatable in vivo. Furthermore, additional transcripts,
      greater than 5 kilobases, presumably mRNA precursors, were found in all RNA
      samples, including those of nonthalassemic controls. The extended transcripts of
      the poly(A) mutants, together with the high molecular weight precursors, suggest
      that the human beta-globin gene transcription unit is significantly longer than
      previously recognized.

PMID- 1374898
TI  - Primary structure of high molecular weight tau present in the peripheral nervous
      system.
AB  - The tau proteins are a family of brain microtubule binding proteins that are
      required during axonal outgrowth and are found in neurofibrillary tangles in
      Alzheimer disease. A protein of higher molecular weight, immunologically related
      to tau, is expressed in the adult peripheral system and in cultured neuronal cell
      lines of neural crest origin. The predicted amino acid sequence of the high
      molecular weight tau from N115 cells has been determined from the sequence of its
      2340-base-pair cDNA. High molecular weight tau contains an open reading frame
      encoding 733 amino acid residues. It contains sequences homologous to those
      present in the N-, middle, and C-terminal domains of adult brain tau proteins,
      including four homologous repeats, which are the tubulin binding sites, and an
      amino acid stretch, which is present only in the N-terminal domain of the mature
      brain variants. The middle region contains a previously unidentified
      nonhomologous stretch of 237 amino acid residues as well as a domain of 66
      residues homologous to exon 6 of the bovine gene that is absent in all bovine,
      rat, and mouse tau cDNAs sequenced so far. A cDNA probe specific to the
      nonhomologous tau insert hybridizes to the 8- to 9-kilobase tau mRNA in N115
      cells but not to the 6-kilobase tau mRNA in brain. Probes for the domains common
      to brain tau isoforms hybridize to both messages. The sequence of high molecular
      weight tau protein also suggests that it, like low molecular weight tau, is an
      elongated hydrophilic molecule. This cDNA should allow us to study the role of
      the domains specific to these tau forms in the specialization of the peripheral
      nervous system and for study of their expression in normal and pathological
      states.

PMID- 1374899
TI  - A leucine-to-proline mutation in the putative first transmembrane domain of the
      22-kDa peripheral myelin protein in the trembler-J mouse.
AB  - Peripheral myelin protein PMP-22 is a potential growth-regulating myelin protein
      that is expressed by Schwann cells and predominantly localized in compact
      peripheral myelin. A point mutation in the Pmp-22 gene of inbred trembler (Tr)
      mice was identified and proposed to be responsible for the Tr phenotype, which is
      characterized by paralysis of the limbs as well as tremors and transient
      seizures. In support of this hypothesis, we now report the fine mapping of the
      Pmp-22 gene to the immediate vicinity of the Tr locus on mouse chromosome 11.
      Furthermore, we have found a second point mutation in the Pmp-22 gene of trembler
      J (TrJ) mice, which results in the substitution of a leucine residue by a proline
      residue in the putative first transmembrane region of the PMP-22 polypeptide. Tr
      and TrJ were previously mapped genetically as possible allelic mutations giving
      rise to similar, but not identical, phenotypes. This finding is consistent with
      the discovery of two different mutations in physicochemically similar domains of
      the PMP-22 protein. Our results strengthen the hypothesis that mutations in the
      Pmp-22 gene can lead to heterogeneous forms of peripheral neuropathies and offer
      clues toward possible explanations for the dominant inheritance of these
      disorders.

PMID- 1374901
TI  - Reduced transcription of the ferredoxin gene in metronidazole-resistant
      Trichomonas vaginalis.
AB  - Metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole] is used to treat
      infections caused by Trichomonas vaginalis, a sexually transmitted human
      parasite. This drug is administered in an inactive form and is reduced to its
      cytotoxic form within the hydrogenosome, an unusual organelle found in
      trichomonads. Metronidazole reduction occurs via ferredoxin-mediated electron
      transport. We have investigated the role of ferredoxin in metronidazole
      resistance. Immunoblot analysis of drug-resistant and -sensitive T. vaginalis
      strains shows that intracellular levels of ferredoxin are invariably reduced in
      the resistant strains relative to a sensitive strain. Similarly, Northern blot
      analysis shows that ferredoxin mRNA levels are reduced 50-65% in resistant
      strains. Using nuclear run-on assays, we show that ferredoxin gene transcription
      is reduced 40-65% in resistant strains. Sequence comparison of the region 5' of
      the ferredoxin gene among drug-sensitive and -resistant strains reveals two point
      mutations, at -178 and -239 nucleotides relative to the start of transcription,
      in a resistant strain. Interestingly, a protein of approximately 23 kDa binds to
      a 28-base-pair region that encompasses the mutation at -239 nucleotides. The
      binding affinity of this protein appears to be reduced in the mutant. These data
      strongly correlate drug resistance with altered regulation of ferredoxin gene
      transcription. A reduction in gene transcription results in decreased
      intracellular levels of ferredoxin. This, in turn, may play a role in
      metronidazole resistance by decreasing the ability of the cell to activate the
      drug.

PMID- 1374900
TI  - 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5''-(4''-amino-1'',2''- oxathiole
      2'',2'-dioxide)pyrimidine (TSAO) nucleoside analogues: highlyselective inhibitors
      of human immunodeficiency virus type 1 that are targeted at the viral reverse
      transcriptase.
AB  - A series of pyrimidine nucleoside analogues containing [2',5'-bis-O-(tert
      butyldimethylsilyl)-3'-spiro-5''-(4''-amino- 1'',2''-oxathiole-2'',2''-dioxide)]
      beta-D-ribofuranose as the pentose were found to inhibit human immunodeficiency
      virus type 1 [HIV-1(IIIB)] replication at a concentration of 0.06-0.8 microM but
      were not cytotoxic at a 1000- to 10,000-fold higher concentration. These
      nucleoside derivatives were also effective against various other HIV-1 strains,
      including those resistant to 3'-azido-3'-deoxythymidine, but not against HIV-2,
      simian immunodeficiency virus, Moloney murine sarcoma virus, or other RNA or DNA
      viruses. They proved to be highly specific inhibitors of the RNA-dependent DNA
      polymerase function of the HIV-1 reverse transcriptase, showing no marked
      inhibition of the HIV-1 reverse transcriptase-associated DNA-dependent DNA
      polymerase activity, HIV-2 reverse transcriptase, DNA polymerase alpha, herpes
      simplex virus 1 DNA polymerase, or Thermus aquaticus DNA polymerase.

PMID- 1374902
TI  - Modulation of L-type calcium channels by sodium ions.
AB  - It is universally believed that the removal of external sodium ions is without
      effect on calcium current. We now report that in enzymatically isolated guinea
      pig ventricular cells, the replacement of external sodium ions with certain other
      cations causes a 3- to 6-fold increase in peak L-type calcium current. The
      increase in current is reversibly blocked by L-type calcium-channel antagonists,
      not mediated by changes in internal calcium, and is inhibited by intracellular 5'
      adenylyl imidodiphosphate, a nonhydrolyzable ATP analogue. The effects of sodium
      removal (and isoproterenol) were almost completely blocked by intracellular
      application of a specific (peptide) inhibitor of cAMP-dependent protein kinase.
      These experiments demonstrate a previously unknown effect of sodium ions to
      modulate calcium-channel phosphorylation via cAMP-dependent protein kinase.

PMID- 1374903
TI  - Detection of acute hepatitis C virus infection by ELISA using a synthetic peptide
      comprising a structural epitope.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed by using a synthetic
      polypeptide (SP) whose sequence was derived from the structural region of
      hepatitis C virus (HCV). Results of several coded panels of sera obtained from
      volunteer blood donors and patients with apparent non-A, non-B hepatitis and/or
      hepatitis B virus used in this ELISA were compared with those of a commercially
      available first-generation C-100 ELISA (using nonstructural HCV antigens), an
      experimental second-generation C-200/C-22 ELISA (using both structural and
      nonstructural HCV antigens), and recombinant immunoblot assays RIBA-I and RIBA
      II. In the majority of cases, the results obtained with the HCV-SP ELISA
      correlated well with those obtained by RIBA-II and C-200/C-22 ELISA. In contrast,
      many samples that were repeatedly reactive in the C-100 ELISA results were
      nonreactive with RIBA and HCV-SP ELISA. In addition, HCV-SP detected HCV-specific
      antibody that appeared within a month of infection and coincided with the
      earliest increase in alanine aminotransferase. In summary, we have developed an
      ELISA based on a structural HCV synthetic polypeptide, HCV-SP, that has high
      specificity and sensitivity and is capable of detecting specific antibodies in
      the acute phase of HCV infection.

PMID- 1374904
TI  - Long-term agonist exposure induces upregulation of beta 3-adrenergic receptor
      expression via multiple cAMP response elements.
AB  - During continuous stimulation by agonist, beta 1- and beta 2-adrenergic receptors
      (ARs) undergo processes that lead to decreases in receptor expression. This
      receptor down-regulation serves to limit the cellular cAMP response during
      chronic agonist exposure. In the recently described third subtype of the beta AR,
      denoted beta 3AR, we found four potential cAMP response elements in the 5'
      flanking region, suggesting that expression of this receptor might be positively
      regulated by agonists. These elements were cloned into the vector pA10CAT2, which
      contains a chloramphenicol acetyltransferase reporter gene, and transiently
      expressed in VERO cells. Three of these elements, TGACTCCA, TGAGGTCT, and
      CGAGGTCA (located 518, 622, and 1125 bases upstream of the beta 3AR coding block,
      respectively) were found to increase transcription of the chloramphenicol
      acetyltransferase gene in response to cAMP analogues and agents that increase
      intracellular cAMP. 3T3-F442A cells, when differentiated into the adipocyte
      phenotype by insulin, expressed beta 3AR, and nuclear runoff studies from such
      cells confirmed cAMP enhancement of beta 3AR mRNA transcription. In these cells,
      beta 3AR mRNA increased in response to exposure to the beta 3AR agonist
      isoproterenol and remained elevated during exposures of up to 24-30 hr. During
      prolonged exposure to agonist, no downregulation of beta 3AR expression in 3T3
      F442A cells occurred. Indeed, beta 3AR expression increased during agonist
      exposure to approximately 165% of basal expression. In marked contrast, beta 1AR
      expression declined by approximately 70% in response to chronic agonist exposure.
      These studies reveal a subtype-specific prolonged transcriptional regulation of a
      beta AR gene by the end product of its signal transduction pathway. Thus, the
      beta 3AR undergoes a paradoxical increase in receptor expression during chronic
      agonist exposure.

PMID- 1374905
TI  - Evidence that Mos protein may not act directly on cyclin.
AB  - Using affinity-purified antiserum we have examined cyclin B2 levels in Xenopus
      oocytes at various stages of oogenesis. We found that cyclin B2 is detected from
      stage 2 to stage 6 as two bands, one of which is phosphorylated, and that cyclin
      B2 mass increases about 28-fold between stage 2 and stage 6. To examine the
      effect of Mos protein on cyclin phosphorylation, we microinjected synthetic
      Xenopus c-mos (c-mosxe) RNA into stages 4, 5, and 6 Xenopus oocytes. In stage 6
      oocytes, maturation was induced by c-mosxe RNA, and, as is the case with
      progesterone treatment, all cyclin B2 was shifted to the phosphorylated form.
      However, c-mosxe RNA injected into stage 4 or 5 oocytes did not induce maturation
      or cause a shift in the relative proportion of the two cyclin B2 bands. These
      data suggest that Mos does not act directly to phosphorylate cyclin B2, causing
      the band shift during maturation. Cyclin B2 synthesis increases about 2-fold
      during maturation, in concert with total protein synthesis. Data from experiments
      on cyclin B2 stability indicate that the half-life of cyclin B2 is about 85 hr in
      stage 6. This suggests that if Mos protein has a direct effect on cyclin
      stability, it does so only at a later stage in oocyte maturation, but not at the
      onset.

PMID- 1374907
TI  - Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions.
AB  - Gamma delta T cells are a distinct lymphocyte population that can exhibit
      reactivity with heat shock proteins over-expressed at inflammatory sites. As
      gamma delta T cells may be involved in the central nervous system (CNS)
      inflammatory process in multiple sclerosis (MS), we examined T-cell populations
      in MS plaque tissue by quantitative immunohistochemistry and sequence analysis of
      T-cell antigen receptor (TCR) delta chains. Gamma delta T cells that express the
      variable (V) gene segments V delta 1, V delta 2, and V gamma 2 (V gamma 9) were
      found to accumulate in acute, demyelinating MS plaques and appeared to have
      undergone clonal expansion, most likely because of recognition of a specific CNS
      ligand. Further, 60-kDa and 90-kDa heat shock proteins (hsp60 and hsp90), which
      may be target antigens for autoreactive gamma delta T cells, were found to be
      expressed in normal CNS tissue and overexpressed in acute MS plaques. In acute
      plaques, hsp60 was found in foamy macrophages, while hsp90 was detected in
      reactive astrocytes. These results provide evidence for a role of gamma delta T
      cells in active stages of MS.

PMID- 1374906
TI  - Characterization of a type II collagen gene (COL2A1) mutation identified in
      cultured chondrocytes from human hypochondrogenesis.
AB  - A subtle mutation in the type II collagen gene COL2A1 was detected in a case of
      human hypochondrogenesis by using a chondrocyte culture system and PCR-cDNA
      scanning analysis. Chondrocytes obtained from cartilage biopsies were
      dedifferentiated and expanded in monolayer culture and then redifferentiated by
      culture over agarose. Single-strand conformation polymorphism and direct
      sequencing analysis identified a G----A transition, resulting in a glycine
      substitution at amino acid 574 of the pro alpha 1(II) collagen triple-helical
      domain. Morphologic assessment of cartilage-like structures produced in culture
      and electrophoretic analysis of collagens synthesized by the cultured
      chondrocytes suggested that the glycine substitution interferes with conversion
      of type II procollagen to collagen, impairs intracellular transport and secretion
      of the molecule, and disrupts collagen fibril assembly. This experimental
      approach has broad implications for the investigation of human chondrodysplasias
      as well as human chondrocyte biology.

PMID- 1374908
TI  - Region-specific expression of a K+ channel gene in brain.
AB  - Northern blot analysis and in situ hybridization studies reveal the highly
      localized expression in rat brain of transcripts from a gene (KShIIIA) encoding
      components for voltage-gated K+ channels. KShIIIA expression is particularly
      prominent throughout the dorsal thalamus. The expression of KShIIIA is compared
      to that of a closely related gene, here called NGK2-KV4. These two genes encode
      transcripts that induce currents in Xenopus oocytes that are as of yet
      indistinguishable, but they show very different patterns of expression in rat
      brain. NGK2-KV4 transcripts are particularly abundant in the cerebellar cortex,
      where KShIIIA expression is very weak. These results demonstrate the existence of
      cell-type-specific K+ channel components and suggest that one reason for the
      unusually large diversity of K+ channel proteins is the presence of subtypes that
      participate in specific brain functions.

PMID- 1374909
TI  - Expression cloning of a rat brain somatostatin receptor cDNA.
AB  - We have used an expression-cloning strategy to isolate a cDNA encoding a
      somatostatin (somatotropin release-inhibiting factor, SRIF) receptor from rat
      cortex and hippocampus. A positive clone was identified by autoradiography after
      binding of radiolabeled SRIF to COS-1 cells previously transfected with pools of
      cDNA clones. The deduced amino acid sequence of the receptor displays sequence
      and structural homology to the family of G-protein-coupled receptors. The
      affinity of various SRIF analogs to the expressed receptor resembles their
      effects on growth hormone release from pituitary cells. In addition, the
      distribution of the mRNA in various tissues corresponds to that described for
      native SRIF receptors. Therefore, we conclude that we have isolated a rat brain
      SRIF receptor cDNA.

PMID- 1374910
TI  - How cytotoxic T cells manage to discriminate nonself from self at the nonapeptide
      level.
AB  - Class I major histocompatibility complex (MHC) antigens are confronted with an
      apparently insurmountable dilemma. Each should show a binding preference to a
      common enough variety of nonapeptides, so that one relevant nonapeptide can be
      found in at least every other viral protein to provoke a cytotoxic T-cell
      response. By so doing, however, the chance of that viral T epitope being self is
      greatly increased. Examination of human and viral nonapeptides preferred by HLA
      B27 led to the following conclusions. (i) In normal cells, peptide fragments
      originating from 5000 or more diverse proteins vie for a finite number of class I
      MHC sites. Consequently, only those nonapeptides having the optimal binding
      affinity to a given class I MHC antigen can gain access to the plasma membrane.
      (ii) Tolerance is rendered only to those host nonapeptides with the optimal
      binding affinity. (iii) Because of the above noted tolerance, viral nonapeptides
      with the optimal binding affinity are invariably ignored. (iv) Viral T epitopes
      actually chosen are always second-echelon nonapeptides that are endowed with
      slightly less than the optimal binding affinity to a given class I MHC antigen.
      (v) Since such second-echelon nonapeptides would not gain access to the plasma
      membrane in normal cells, the issue of self or nonself is rendered irrelevant by
      this choice. (vi) Since viral T epitopes are of this type, cytotoxic T-cell
      responses against infected cells are expected to be effective only when a few
      viral proteins are made in large amounts at the expense of host proteins.

PMID- 1374911
TI  - Induction by fungal elicitor of S-adenosyl-L-methionine synthetase and S-adenosyl
      L-homocysteine hydrolase mRNAs in cultured cells and leaves of Petroselinum
      crispum.
AB  - Treatment of cultured parsley (Petroselinum crispum) cells with fungal elicitor
      rapidly activates transcription of many genes encoding specific steps in pathogen
      defense-related pathways. We report evidence that three cDNAs corresponding to
      such genes represent two key enzymes of the activated methyl cycle. Two cDNAs are
      derived from distinct members of the S-adenosyl-L-methionine synthetase gene
      family, based on extensive similarity of the deduced polypeptides with authentic
      enzymes from Arabidopsis thaliana, rat, yeast, and Escherichia coli. The third
      cDNA exhibits large similarity with a functionally related gene, encoding S
      adenosyl-L-homocysteine hydrolase, from rat and a slime mold. Marked differences
      in the mRNA levels occurred in different organs of parsley plants. Elicitor
      treatment strongly induced both mRNAs in cultured cells as well as intact leaves
      and led to marked increases in S-adenosyl-L-homocysteine hydrolase enzyme
      activity. These results suggest a close metabolic link between pathogen defense
      and an increased turnover of activated methyl groups.

PMID- 1374914
TI  - A 'crisis' that can be overcome: management of sickle cell disease.

PMID- 1374912
TI  - Tumor necrosis factor alpha is an autocrine growth regulator during macrophage
      differentiation.
AB  - Previous experiments have revealed the expression of tumor necrosis factor alpha
      (TNF-alpha) transcripts in all murine bone marrow-derived macrophage colonies
      isolated from days 5 through 9 of differentiation in vitro. These results
      implicated a role for TNF-alpha gene expression during macrophage
      differentiation. Antisense oligomers to the initiation region of the TNF-alpha
      message were used to inhibit its expression, thus allowing the role of TNF-alpha
      gene expression in controlling the differentiation of macrophages to be
      determined. Results showed that TNF-alpha regulated the proliferation of
      macrophages during differentiation. Cells isolated on day 3 were exclusively
      vulnerable to the effects of blocking TNF-alpha gene expression, displaying a 30%
      increase in proliferation over control cells or sense oligomer-treated cells.
      Thus, in the absence of TNF-alpha gene expression, cells maintained proliferation
      instead of undergoing terminal differentiation. Exogenous TNF-alpha was capable
      of rescuing day 3 antisense-treated cells, therefore maintaining normal levels of
      proliferation. In contrast, blocking interleukin 1 beta gene expression by
      antisense oligonucleotide treatment had no effect on proliferation. Addition of
      exogenous recombinant murine or human TNF-alpha decreased the total cell number
      25-50% regardless of whether cells were grown in medium containing colony
      stimulating factor 1 (CSF-1) or granulocyte-macrophage colony-stimulating factor
      (GM-CSF). These results suggested that exogenous TNF-alpha suppressed
      proliferation of early hematopoietic progenitors, whereas endogenous TNF-alpha
      regulated proliferation of macrophage progenitors. The number of differentiated,
      adherent macrophages on day 5 of differentiation in vitro was increased by TNF
      alpha treatment of GM-CSF-induced macrophages but was suppressed in CSF-1-induced
      macrophages. These findings suggest that distinct TNF receptor expression and/or
      signaling is induced in differentiating macrophages stimulated with either growth
      factor.

PMID- 1374913
TI  - Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger
      cDNA.
AB  - The Na+/Ca2+ exchanger plays important roles in Ca2+ handling in many excitable
      cells. In particular, the Na+/Ca2+ exchanger is expressed at high levels in the
      cardiac sarcolemma and is the dominant mechanism of Ca2+ extrusion from the
      cells. In addition, the exchanger has been suggested to play key roles in
      digitalis action and in postischemic reperfusion injury of cardiac myocytes. We
      report here the isolation and characterization of the cDNA encoding the human
      cardiac Na+/Ca2+ exchanger. Twelve overlapping clones corresponding to 5.6
      kilobases of the exchanger cDNA sequence were isolated from 5 x 10(5) phage
      plaques screened. The sequence predicted a 973-amino acid polypeptide with a
      putative leader peptide, 11 potential membrane-spanning regions, and one large
      putative cytoplasmic loop between the fifth and sixth transmembrane helices. When
      RNA was synthesized in vitro from the cloned cDNA and injected into Xenopus
      oocytes, it induced expression of Na+/Ca2+ exchange activity at high levels,
      confirming that this clone encodes the functional Na+/Ca2+ exchanger. Southern
      blot analysis indicated that the cardiac exchanger gene exists as a single copy
      in the human genome, although existence of other related genes cannot be ruled
      out. Northern blot and S1 mapping analyses revealed that the cardiac type
      exchanger mRNA is expressed most abundantly in the heart and next in the brain.
      The cardiac-type exchanger mRNA was also expressed in the retina and in skeletal
      and smooth muscles at very low levels. The levels of mRNA encoding the exchanger
      were significantly lower in fetal hearts than in adult hearts but were unchanged
      in the myocardium from patients with end-stage heart failure.

PMID- 1374916
TI  - [Histochemical representation of acetylcholinesterase in Alzheimer's disease].
AB  - Senile plaques in the cerebral neocortex, entorhinal cortex and hippocampus are
      reactive for Acetylcholinesterase (AChE). The same types of plaques are observed,
      as with immunostains for beta-protein, including the very simple ones, consisting
      nearly exclusively of loose deposits of beta-protein. If there are many plaques,
      the normal network of AChE-positive axons disappears. Explanations for both, the
      apparent shift of AChE from the axons to the plaques on the one hand and the very
      early development of AChE positive deposits during the plaque development on the
      other hand are sought.

PMID- 1374915
TI  - Impairment of albuterol-induced suppression of food intake in diabetes mellitus.
AB  - Albuterol (salbutamol), a beta 2 adrenoreceptor agonist, produced a dose
      dependent decrease in food intake in Sprague-Dawley male control rats. This
      phenomenon appeared to be impaired in streptozotocin (STZ) diabetic rats. The
      density of beta 2 adrenoreceptors in the ventromedial hypothalamic nucleus was
      increased as a function of diabetes. In contrast, a decrease in the ventromedial
      hypothalamic 5-hydroxyindoleacetic acid (5-HIAA) concentration, an indicator of
      serotonin (5-hydroxytryptamine; 5-HT) release or turnover rate, was observed in
      this disease state. Neither the beta 2 adrenoreceptor level nor 5-HT turnover
      rate was altered in the periventricular hypothalamic nucleus of STZ diabetic
      rats. The concentrations of 5-HT in both hypothalamic nuclei were unchanged in
      these animals. Neurochemical and behavioral abnormalities featured in the
      diabetic state were reversed with institution of insulin therapy. These data
      conclude that diabetes-related impairment in the anorexic action of albuterol may
      be due to derangements in ventromedial hypothalamic beta 2 adrenoreceptor
      function.

PMID- 1374917
TI  - [Changes of microenvironment and tumor cell heterogeneity--consequences for
      bioptic diagnosis].
AB  - During the last several decades, immunohistochemical studies of tumors, along
      with other approaches, have suggested that the clinical and biological
      progression results, at least in part, from the sequential appearance within the
      neoplasm of cellular subpopulations whose new characteristics reflect specific
      somatic genetic changes. However, CNS may provide a different microenvironment
      for activation and proliferation than other tissues. The tissue-specific
      distribution of intermediate filament proteins, in particular the keratins,
      permits their use as marker in histopathology, but several important exceptions
      are recognized. In this connection, it is of interest that, according to the
      other reports, glial tumors may be positive for different anti-keratin
      antibodies. However, the gliomas did not show an immunoreaction in any of the
      cases when HEA-125 and Ber-EP4 were applied. The great number of multihormonal
      pituitary adenomas and possible change of the immunohistochemically detectable
      hormone status in cases of recurrent tumors have particularly re-emphasized the
      need for new thinking about patterns of classification. The diagnosis of
      malignant melanoma has been considerably facilitated recently by the introduction
      of immunohistological labelling with antibodies selective against melanoma
      antigen (HMB-45). Our results confirmed the necessity of cautious interpretation
      of HMB-45 immunoreactivity because a HMB-45 expression can be observed in several
      non-melanotic tumors.

PMID- 1374918
TI  - Type VIII collagen in the normal and diseased human brain.
AB  - Type VIII collagen has been localized to specialized extracellular matrices in
      fetal tissues and has been suggested to be associated with cellular proliferation
      and angiogenesis (Sage and Iruela-Arispe 1990). In view of this hypothesis we
      studied its distribution in the normal and diseased human brain. Focal
      immunoreactivity was seen in histologically abnormal vessels of all 10 angiomas
      and 40 of 52 brain tumors. Staining was very weak in 3 embryonal and fetal
      brains, and it was absent in 20 normal adult brains and in 15 adult brains
      showing various cerebrovascular abnormalities. Our results provide additional
      evidence for the participation of type VIII collagen in some types of
      angiogenesis.

PMID- 1374919
TI  - [Immunohistochemical studies of intermediate filament type in the human
      hypophysis and in adenoma].
AB  - The paper describes the value of immunohistologically estimated differences in
      the intermediate filament protein composition of the different cell types of
      human adenohypophysis and the corresponding pituitary adenomas. Interestingly,
      some tumors failed to express any type of intermediate filament proteins, whereas
      other coexpress cytokeratins and vimentin/or neurofilament protein.

PMID- 1374920
TI  - [The frequency of gliovascular heterotopies (dysplasias)].

PMID- 1374921
TI  - Rapid development of giant aneurysm at the base of the brain in an 8-year-old boy
      with perinatal HIV infection.
AB  - An 8-year-old boy with perinatal HIV infection developed a large fusiform
      aneurysm in the circle of Willis two years prior to death which was confirmed by
      radiological studies. The postmortem examinations revealed a predominantly
      intimal, proliferative lesion, and partial destruction of the internal elastic
      lamina in the involved arteries. Within the intima hyperplasia of fibroblasts and
      smooth muscle cells was observed. No inflammatory alterations, no granulomas and
      no multinucleated giant cells could be noted in the vascular walls and in the
      cerebral parenchyma. A small ischemic infarct was present in the left thalamus.
      Cerebellum, brainstem and medulla showed multiple areas of progressive multifocal
      leukoencephalopathy (PML). Immunohistochemistry with anti-gp41, a monoclonal
      antibody against HIV envelope did not exhibit any positive results. These
      findings implicate that the vascular lesion might be attributed to primary
      infection of the brain by HIV which led to a defect of elastic lamina and
      consecutive intimal hyperplasia. A second hypothesis could be based on the effect
      of extremely high dose AZT therapy avoiding inflammatory reaction after HIV
      infection.

PMID- 1374922
TI  - Azelastine potentiates the prostaglandin-induced increase of cyclic AMP content
      in human platelets and in guinea-pig alveolar macrophages.
AB  - The effect of azelastine on intracellular cyclic AMP concentration and on various
      indexes of cell activation was evaluated in guinea-pig alveolar macrophages and
      in human platelets. The effect of azelastine was further investigated on
      adenylate cyclase activity using membranes and homogenates from guinea-pig
      alveolar macrophages. Pretreatment of alveolar macrophages with azelastine
      prevented the activation induced by PAF-acether and by the chemotactic peptide
      fMLP as estimated by the reduced liberation of arachidonic acid metabolites
      formed by the cyclooxygenase and the lipoxygenase pathways. The effect of
      azelastine was concentration-dependent (50 to 500 microM) and reversible.
      Similarly, a short pretreatment with azelastine (100 microM) prevented
      arachidonic acid-induced platelet aggregation. This effect was also reversible
      after washing the platelets. In guinea-pig alveolar macrophages, azelastine
      induced a concentration-dependent (10 to 500 microM) increase in intracellular
      cyclic AMP and markedly potentiated the increase induced by PGE2. In human
      platelets, azelastine alone increased intracellular cyclic AMP concentration
      marginally only but, as in the case of macrophages, synergized with PGI2.
      Azelastine did not activate significantly adenylate cyclase unless a cytosolic
      factor was included within the membrane fraction. This effect of azelastine was
      not due to Ca2+ movements and was not modified by GTP. Our findings show that
      azelastine interferes with cell activation through a mechanism related to an
      increase in intracellular cyclic AMP concentration. The increase in cyclic AMP
      was induced by azelastine in intact cells and in homogenates but not in a crude
      membrane fraction. Those results indicate that azelastine modifies a cytosolic
      factor that may be phosphodiesterase. In addition, similarities between the
      effects of azelastine and those of reference phosphodiesterase inhibitors
      (theophylline, isobutyl-methyl-xanthine) are shown in this study, suggesting that
      azelastine might behave as a phosphodiesterase inhibitor.

PMID- 1374923
TI  - Intraarterial injection therapy of newly developed cisplatin-phosphatidyl choline
      lipiodol suspension for hepatocellular carcinoma.
AB  - Twenty-seven patients with hepatocellular carcinoma were treated by intraarterial
      injection of a suspension of cisplatin powder and iodized oil using phosphatidyl
      choline as a dispersing stabilizer. A reduction in tumor size of over 25% was
      obtained in 23 patients (85%) and a reduction of more than 50% was obtained in 17
      patients (63%). In all of 14 patients with a high serum alpha-fetoprotein level
      (more than 200 ng/ml), 27% to 99% reduction in the level was obtained. The one-,
      two-, and three-year survival rates were 74%, 50%, and 35%, respectively. As for
      side effects, digestive symptoms were rather frequently observed. Liver abscess
      and cholangitis were observed in one patient each in patients combined with
      embolization using gelatin sponge particles. Injection of the suspension with
      embolization was superior to injection only in therapeutic effect, but was
      associated with a higher frequency of side effects. The therapeutic effect was
      better in cases of higher Lipiodol retention in the tumor on follow-up CT.

PMID- 1374924
TI  - Analysis of patients treated with radiotherapy in the year 1990.
AB  - We analyzed the patients treated with radiotherapy in Gunma University Hospital
      in 1990, to determine the characteristics of the practice of radiotherapy. During
      this period, 540 patients with various diseases received radiation therapy. Five
      hundred thirty-one (98.3%) of them had malignant tumors, and the remaining nine
      had benign diseases. Of the patients with malignant tumors, primary tumor of the
      head and neck (21.7%), and lung and mediastinum (13.0%) were most common. Four of
      nine patients with benign diseases had pterygium. Three hundred thirty-two
      patients (63%) had previously untreated malignant tumors. Curative radiotherapy
      was performed in 296 patients (56%), and palliative radiotherapy in 235 (44%). Of
      CRG patients, 43% were treated with radiation alone and 40% with surgery followed
      by radiotherapy. The proportion who received curative radiotherapy was the
      highest in patients with cervical cancer (80%). Twenty-four of 34 patients
      treated with intracavitary irradiation had cervical cancer. Interstitial
      irradiation was performed in nine patients. Four patients with pterygium were
      treated postoperatively with surface irradiation using an Sr-90 contact device.
      Radioactive iodine was administered to ten patients: eight thyroid cancer
      patients and two hyperthyroid patients.

PMID- 1374925
TI  - Time-course of capsaicin-evoked release of calcitonin gene-related peptide from
      rat spinal cord in vitro. Effect of concentration and modulation by Ruthenium
      Red.
AB  - The capsaicin-evoked release of calcitonin gene-related peptide (CGRP) from rat
      superfused dorsal spinal cord slices was investigated during sustained capsaicin
      exposure thought to represent equilibrium conditions. The dose-effect
      relationship for total peptide release evoked by single capsaicin doses (26 min
      exposure) was very steep with a threshold at 0.06 microM and a maximum at 0.3
      microM capsaicin. With concentrations of capsaicin within this range the slow
      decline of the peptide release in the presence of capsaicin was not a consequence
      of exhaustion of an available peptide pool nor of neuronal impairment because
      potassium depolarization was still able to release CGRP. In contrast, with
      concentrations of capsaicin at 1.5 microM and above, there was a much faster
      decay of the release after the peak, most probably due to a loss of the secretion
      capacity caused by neuronal inactivation. When cumulative dose regimens for
      capsaicin were employed, release of CGRP could be stimulated only up to a dose of
      1-1.5 microM capsaicin; further increase in capsaicin concentration was
      ineffective. This was also most probably due to a loss of the secretion capacity
      caused by neuronal inactivation and not caused by depletion of a releaseable
      peptide pool. Release of CGRP evoked by capsaicin concentrations in the range of
      0.1-0.3 microM in either dosage protocol was reduced in the presence of Ruthenium
      Red (RR, 2.5 microM). RR did not reduce neuropeptide release evoked by capsaicin
      concentrations at or above 1-1.5 microM, nor did it affect the inactivation of
      the release process at such high capsaicin concentrations. The results
      demonstrate that, upon sustained exposure to capsaicin, different ranges of
      concentration can be established at which either only stimulatory or a mixture of
      stimulatory and inhibitory effects determine the amount of neuropeptides
      released.

PMID- 1374926
TI  - Specificity of oligonucleotide probes complementary to evolutionarily variable
      regions of 16S rRNA from Mycoplasma hyopneumoniae and Mycoplasma hyorhinis.
AB  - Mycoplasma is the common name for the smallest free-living microorganisms, the
      Mollicutes. Mycoplasma hyopneumoniae is of great importance in veterinary
      medicine, causing enzootic pneumonia in pigs. M hyorhinis can cause polyserositis
      and may cause pneumonia in piglets. Oligonucleotides complementary to variable
      regions of 16S rRNA from these mycoplasmas were designed and used as probes for
      detection and identification of these mycoplasmas. The probe complementary to 16S
      rRNA of M hyorhinis gave a very weak cross-hybridisation with M hyosynoviae in
      filter hybridisation experiments, but not with any of the other porcine
      mycoplasmas tested. Three oligonucleotide probes complementary to M hyopneumoniae
      16S rRNA were tested. One of the probes (Mhp6/30) was found to be specific to M
      hyopneumoniae, but the other two gave cross-hybridisation with M flocculare.
      Using the Mhp6/30 probe in direct filter hybridisation experiments, it proved
      possible to detect M hyopneumoniae in lung biopsies from experimentally infected
      pigs.

PMID- 1374927
TI  - Immunocytochemical detection of amylase, carboxypeptidase A, carcinoembryonic
      antigen and alpha 1-antitrypsin in carcinomas of the exocrine pancreas of the
      dog.
AB  - The immunocytochemical detection of amylase, carboxypeptidase A, alpha 1
      antitrypsin, carcinoembryonic antigen (CEA) and keratin in normal canine
      pancreatic tissue and in carcinomas of the exocrine pancreas of the dog is
      described. In the normal pancreas, the acinar cells contain amylase,
      carboxypeptidase and alpha 1-antitrypsin. The pancreatic ducts react with the
      antikeratin antibody. Twelve out of 14 pancreatic exocrine carcinomas showed
      immunoreaction with antiamylase antibody, and 10 with anticarboxypeptidase
      antibody. Five neoplasms reacted with anti-CEA antibody and three with the anti
      alpha 1-antitrypsin antibody. It was not possible to find any systematic
      difference in the immunocytochemical profiles of acinar, tubular and
      undifferentiated carcinomas. These results indicate that immunocytochemical
      marking of amylase and carboxypeptidase is of value in the diagnosis of
      pancreatic neoplasms in the dog, especially if metastasis is the only material
      available for study and the tumour does not show any diagnostic feature on
      routine light microscope preparations.

PMID- 1374930
TI  - [The picture nursing care plan: a tool in geriatrics].

PMID- 1374928
TI  - In vivo assessment of drug sensitivity of African trypanosomes using the
      akinetoplastic induction test.
AB  - Following treatment of mice infected with Trypanosoma congolense or T brucei
      brucei with various doses of isometamidium chloride or diminazene aceturate, the
      induction of akinetoplastic (AK) forms was observed in the trypomastigotes of
      both species within 10 hours of drug administration. The levels of AK-induction
      were closely correlated with the levels of resistance to each compound found
      using a standard in vivo drug assay in mice. In general, ineffective doses of
      either compound conferred AK-induction rates of less than 30 per cent; relapsing
      cases had between 30 and 50 per cent while curative doses had AK-induction rates
      of 50 per cent or more. In vivo determination of AK-induction rates using
      ordinary light microscopy is thus a potentially feasible alternative indicator to
      the conventional use of mice infection and treatment methods for assessing drug
      sensitivity in African trypanosomes.

PMID- 1374929
TI  - Isolation and preliminary characterisation of a novel retrovirus isolated from a
      leukaemic dog.
AB  - A novel canine retrovirus was isolated from mononuclear cells of the peripheral
      blood of a leukaemic dog. The main clinical and pathological findings in this dog
      were lethargy, anorexia, weakness, dyspnoea, severe anaemia, thrombocytopenia and
      a high white blood cell count, practically all of which were lymphoblasts. The
      virus was isolated from mononuclear cells obtained from the blood, cocultivated
      with indicator cells. The virus particles encode a reverse transcriptase with
      Mg++ preference, have a density in sucrose gradients of 1.16 g ml-1, and induce
      syncytia in permissive cell cultures such as Himalayan tahr ovary and canine
      fetal thymus lines. This agent replicates to high titres. The virus exhibits a
      morphogenesis and morphology typical of lentiviruses. Immunoblotting and
      competitive radioimmunoassays failed to detect immunological crossreactivity with
      other representative lentiviruses and oncoviruses of the retrovirus family.

PMID- 1374931
TI  - [Nursing and palliative care].

PMID- 1374932
TI  - The patch clamp technique.

PMID- 1374933
TI  - Single lung transplantation for eosinophilic granulomatosis.
AB  - A 26-year-old woman with end-stage lung disease due to eosinophilic
      granulomatosis had single right lung transplantation with an excellent function
      result that persists beyond 9 months of follow-up. Single lung transplantation
      offers excellent palliation to selected patients with end-stage lung disease.

PMID- 1374935
TI  - Growth cones and structural variation of synaptic end-bulbs in the cochlear
      nucleus of the adult cat brain.
AB  - To explore the potential for structural variation and new growth at the synapse,
      we studied the morphological patterns of the end-bulbs of cochlear nerve axons in
      adult cats by using rapid Golgi, reduced silver, and electron microscopic
      methods. Horseradish peroxidase labeling of these endings in the anterior
      division of the antroventral cochlear nucleus was produced by anterograde
      transport following injection into the cochlea. Three types of end-bulbs were
      distinguished, regardless of method: reticular, coalescent, and ringed forms, all
      synapsing on spherical bushy cells. The reticular variety corresponds to the
      classically described end-bulb and constitutes the majority in all regions of the
      tonotopic map. The ringed end-bulb, described here for the first time, forms an
      excitatory synaptic cuff around the base of a bushy cell's main dendrite; these
      endings were localized to the region receiving cochlear input in the 1-6 kHz
      range, which is used in vocalization. The coalescent ending forms a small
      fraction of the end-bulb population throughout the region studied. The findings
      raise the possibility of functional differences between these synaptic types.
      Growth cones and retraction clubs were present on most, if not all, of the end
      bulbs in every adult cat studied. A systematic survey of the end-bulb patterns
      revealed a continuous gradient of variation, in which each synaptic type forms a
      distinct mode. These findings lead us to hypothesize that the end-bulbs are in a
      continual state of structural and functional flux. These endings should prove
      useful for studies on the modifiable properties of central synapses.

PMID- 1374934
TI  - [Hodgkin's disease and infection with human immunodeficiency virus].
AB  - Three patients with Hodgkin's disease, mixed cellularity subtype, plus infection
      by human immunodeficiency virus are presented. Two of them were intravenous drug
      abusers, and one had promiscuous heterosexual behaviour; they all presented B
      type symptoms. One patient died because of infection, whereas the other two
      persisted in complete remission after treatment at 4 and 5 years of follow-up,
      respectively. None of the patients still alive has developed AIDS. The criteria
      for considering Hodgkin's disease as an AIDS-related lymphoproliferative disorder
      are discussed.

PMID- 1374936
TI  - Effect of thiol group modification on ion flux and ligand binding properties of
      the GABAA-benzodiazepine receptor chloride channel complex.
AB  - Agents that modify thiol groups have been shown to alter ligand binding at a
      variety of receptor sites. In addition, alkylation of sulfhydryls has been shown
      to block ion channel conductance. We studied the effects of thiol reagents on
      gamma-aminobutyric acid (GABA)-activated chloride flux (36Cl-) and [3H]-diazepam
      binding in mouse brain membrane preparation (microsacs). Incubation of microsacs
      in the presence of: mercuric chloride (HgCl2), p-chloromercuriphenylsulfonic acid
      (pCMBS), hydroxymercuribenzoate (HMB), n-ethylmaleimide (NEM), or iodoacetic acid
      (IAA) attenuated GABA-stimulated Cl- uptake. The thiol reagents reduced both
      maximal stimulation and the potency of GABA to induce Cl- uptake. Thiol reagent
      treatment decreased the affinity of high-affinity [3H]-muscimol equilibrium
      binding. Supernatant prepared from microsacs treated with pCMBS stimulated Cl-
      uptake in the absence of GABA agonist in microsacs unexposed to thiol reagents.
      The supernatant taken from pCMBS-treated microsacs also stimulated [3H]-diazepam
      binding. This effect was blocked by the addition of the GABA receptor antagonist
      bicuculline. The concentration of endogenous GABA in supernatant from pCMBS
      treated microsacs was sixfold greater than that in supernatant from control
      microsacs. This increase in levels of endogenous GABA by thiol reagents was due
      to both an increase in GABA release and a decrease in high-affinity GABA uptake.

PMID- 1374937
TI  - Selective subregional dopamine depletions in the rat caudate-putamen following
      nigrostriatal lesions.
AB  - Previous work has demonstrated a complex neurochemical and neuroanatomical
      heterogeneity of the striatum in normal brains. The present research investigated
      whether the heterogeneous distribution of dopamine would be altered following
      unilateral injections of the neurotoxin 6-hydroxydopamine into the substantia
      nigra of the rat. Four weeks following injection, the nucleus accumbens and
      subregions of the caudate-putamen and substantia nigra were dissected and
      analyzed by HPLC with electrochemical detection for dopamine, 5
      hydroxytryptamine, and their respective metabolites. Levels of dopamine and its
      metabolites in the anterodorsolateral caudate-putamen were depleted more than
      medial, posterior, and ventral, striatal areas in partially lesioned animals
      (less than 90% dopamine depletion). This resulted in an alteration of striatal
      heterogeneity such that a mediolateral gradient of dopamine tissue content was
      now superimposed on the normal rostrocaudal gradient observed in controls.
      Paralleling these findings, dopamine was more depleted in the lateral, as opposed
      to the medial, substantia nigra. These results indicate that the nigrostriatal
      dopamine system degenerates in a heterogeneous fashion following 6
      hydroxydopamine administration. It is speculated that the differential loss of
      dopamine neurons observed in the nigra of Parkinson's patients may be due to a
      differential sensitivity to toxins within the nigra.

PMID- 1374939
TI  - Parasympathetic innervation of the rat thymus during first life period:
      histochemical and biochemical study.
AB  - In the present study we analyzed development of the rat thymus parasympathetic
      innervation using histochemical determination of distribution and density of
      acetylcholinesterase (AChE) positive nerve profiles, as well as biochemical
      measuring of the activity of this enzyme. Rat thymuses from late embryonal to
      adult periods of life were analyzed. The AChE-positive nerve profiles were found,
      for the first time, on day 18 of fetal life in capsule and interlobulary septae,
      but also in the subcapsulary and cortico-medullary areas. The density of these
      profiles increased during the thymic development. The AChE positive nerve
      profiles in subcapsulary region were observed mainly in close proximity to the
      thymic epithelial cells, while in the cortico-medullary region they were found in
      apposition to the thymocytes. The biochemical analysis showed that the specific
      AChE activity in rat thymus was high on day 19 of gestation. A significant
      increase in the activity of this enzyme was measured by the third day of
      postnatal development, and its activity remained approximately at the same level
      up to the day 90. The present results suggest that thymus receives
      parasympathetic innervation relatively early in ontogeny; in addition, these
      nerve fibers could be involved in the regulation of the organ activity, at least,
      through action upon the thymocytes and/or by modulation of the thymic epithelial
      cell activity.

PMID- 1374938
TI  - Acute toxicity of tri-n-butyltin chloride (TBTC) in the Syrian golden hamster.
AB  - The effects of tri-n-butyltin chloride (TBTC) on Syrian golden hamsters were
      studied. TBTC in single doses of 0, 29.6, 44.4, 66.7, 100 or 150 mg/kg were given
      to 10 male hamsters in each group and the mortality rates were determined two
      weeks thereafter. They were 0% (0/10), 0% (0/10), 10% (1/10), 10% (1/10), 30%
      (3/10) and 70% (7/10) for 0, 29.6, 44.4, 66.7, 100 and 150 mg/kg groups,
      respectively. In the case of females, seven groups consisting of 10 animals each
      were given TBTC at doses of 0, 29.6, 44.4, 66.7, 100, 150, or 225 mg/kg. The
      mortality rates determined two weeks after the TBTC treatment were 0% (0/10), 10%
      (1/10), 10% (1/10), 0% (0/10), 40% (4/10), 30% (3/10) and 90% (9/10) for 0, 29.6,
      44.4, 66.7, 100, and 225 mg/kg groups, respectively. Based on these mortality
      data, the LD50s via oral administration were determined as 146.9 mg/kg (95% C.I.
      111.8-193.3 mg/kg) for the male and 172 mg/kg (95% C.I. 127.2-233.4 mg/kg) for
      the female. Regarding pathological changes, animals experienced lesions in the
      bile duct, such as the dilatation of the common bile duct and cholestasis, and/or
      adhesion of the bile duct to the liver, gallbladder, pancreas and duodenum. In a
      separate experiment, a single dose of 44.4 mg/kg TBTC was administered orally to
      12 male hamsters, then the concentrations of TBTC and its metabolite, di-n
      butyltin chloride (DBTC), in the liver were analyzed by means of gas
      chromatography for 14 days after the treatment. The maximum concentrations of
      TBTC and DBTC appeared one day after the administration, and decreased rapidly
      thereafter. The concentration of DBTC was found to be higher than that of TBTC
      throughout the experimental period.

PMID- 1374940
TI  - Anti-hepatitis C virus (HCV) screening at a Canadian Red Cross center:
      significance of a positive c100 HCV enzyme-linked immunosorbent assay.
AB  - The c100 hepatitis C virus (HCV) enzyme-linked immunosorbent assay (ELISA) has
      been used to screen blood donors to prevent transfusion-associated non-A,non-B
      hepatitis. This test is not specific, and only about 25 percent of c100 HCV ELISA
      positive blood samples appear to transmit hepatitis C. However, the intensity of
      the ELISA (sample/cutoff ratio [S/C], greater than 2) could identify a
      subpopulation of donors that are at high risk for transmitting hepatitis. Blood
      samples from 20,186 volunteer blood donors at a Canadian Red Cross blood
      transfusion center were screened for antibodies to HCV using the c100 HCV ELISA.
      Fifty-nine (0.3%) of these donors were repeatably reactive on ELISA. When their
      samples were tested with the c100 recombinant immunoblot assay (RIBA) and second
      generation RIBA (RIBA-2), 26 (44%) and 31 (52%) samples, respectively, were found
      to be positive. Thirty-three of the 59 ELISA-reactive donors had an S/C greater
      than 2. Of these 33 donors, 30 (91%) had elevated alanine aminotransferase (ALT),
      27 (82%) were RIBA-2 positive, and 22 (67%) had risk factors for hepatitis. In
      contrast, of the 26 ELISA-reactive donors with S/C less than 2, only 7 (27%) had
      elevated ALT, and 4 (15%) were RIBA-2 positive and also had high risk factors for
      hepatitis. Thus, while the HCV ELISA may lack specificity, its intensity can
      serve to identify a subgroup of donors that are at high risk for transmitting
      hepatitis.

PMID- 1374941
TI  - Is the multidrug transporter a flippase?
AB  - The phenomenon of multidrug resistance is correlated with the presence of a
      membrane protein, P-glycoprotein, which pumps a wide variety of drugs out of
      cells thus reducing their toxicity. However, the mechanism of this pumping action
      remains unclear. In this article, we suggest that several properties of the
      multidrug transporter may be explained if it acts as a 'flippase' to transport
      drugs from the inner leaflet of the lipid bilayer to the outer or to the external
      medium.

PMID- 1374942
TI  - RNA editing: in Chloroplast and brain.

PMID- 1374943
TI  - Rapid isolation of human CD34 hematopoietic stem cells--purging of human tumor
      cells.
AB  - Human CD34+ hematopoietic stem cells were purified using a new technology in
      which monoclonal antibodies are covalently immobilized on polystyrene surfaces.
      The CD34+ cell isolation scheme involved three sequential processes: (1)
      purification of bone marrow mononuclear cells; (2) enrichment of CD34+ cells
      using covalently immobilized soybean agglutinin; and (3) positive selection of
      CD34+ cells using polystyrene surfaces coated with the anti-CD34 monoclonal
      antibody ICH3. CD34+ cells purified by this process have both low-to-medium
      forward light scatter and low 90 degrees light-scatter properties. Moreover, the
      purified CD34+ cells are greater than 85% viable, express appropriate
      characteristic surface antigens, and are 10-50-fold enriched in short- and long
      term hematopoietic activity. CD34+ cells collected in this manner from bone
      marrow samples contaminated with radiolabeled breast carcinoma, neuroblastoma,
      acute myelogenous leukemia, or small cell lung carcinoma cells were 99.9%
      depleted of the tumor cells. The CD34+ cell selection devices are sterile and are
      easily scaled-up to process clinical scale bone marrow samples.

PMID- 1374945
TI  - A polymorphic human kidney-specific non-MHC alloantigen. Its possible role in
      tissue-specific allograft immunity.
AB  - Tissue specific non-MHC alloantigens play a crucial role in allograft immunity.
      However, their structural properties have remained elusive, largely due to their
      inability to induce a strong antibody response. We report the characterization of
      a monkey heteroantiserum, MHK-I, raised against human kidney cells, that
      serologically reacts specifically with kidney cells after extensive absorptions
      of anti-HLA class I and II reactivities. The non-MHC MHK-I-binding molecule(s) is
      expressed only in the renal cortex on the glomerulus, peritubular capillaries,
      venous endothelium, and tubular epithelium. Immunochemically, MHK-I recognizes a
      kidney-specific non-MHC alloantigen of Mr 90,000 to 100,000 (90 kD). These
      properties of MHK-I are similar to those of the previously characterized
      alloantibodies eluted from rejected kidneys. These alloantibodies bind to the
      kidney from which the antibody was eluted and to a few others but are unlike MHK
      I, which binds to extracts prepared from all human kidneys. Biochemical analysis
      by two-dimensional electrophoresis (pI ranging between 4.5 and 5.5) and peptide
      fingerprinting provide further evidence that the alloantigen is polymorphic.
      These findings imply that the non-MHC kidney-specific molecule(s) may function as
      target(s) for immune destruction of renal allografts.

PMID- 1374944
TI  - Conversion of liver allograft recipients from cyclosporine to FK506
      immunosuppressive therapy--a clinicopathologic study of 96 patients.
AB  - The effect of conversion from cyclosporine-steroid immunosuppression to the new
      agent FK506 was studied in 96 liver allograft recipients who were experiencing
      graft dysfunction or cyclosporine toxicity. Patients were stratified according to
      the cause of graft dysfunction that ultimately led to conversion to FK506.
      Response to FK506 introduction was monitored pathologically and biochemically.
      The outcome of a switch from CsA to FK506 was highly favorable in patients
      experiencing acute and the early stages of chronic rejection, despite optimal
      conventional therapy. Patients with later stages of chronic rejection did not
      respond to conversion to FK506 and most eventually lost their liver grafts in
      this process. Patients in whom we had difficulty separating chronic rejection
      from chronic persistent or low-grade chronic active hepatitis were mostly
      unaffected by conversion to FK506. Active hepatitis was a poor indication for
      conversion, because most of the patients experienced graft failure or died from
      liver failure. As a group, there was no statistically significant change in renal
      function 180 days after conversion to FK506. These findings expand the experience
      with FK506 in human liver allograft recipients.

PMID- 1374946
TI  - Evidence that umbilical cord blood contains a higher frequency of HLA class II
      specific alloreactive T cells than adult peripheral blood. A limiting dilution
      analysis.
AB  - Umbilical cord blood has been used to effect hematological reconstitution and
      there are sufficient stem cells available in the cord blood obtainable from a
      single placenta to reconstitute an adult patient. Umbilical cord blood might
      therefore, have widespread potential use in the field of bone marrow
      transplantation. We compared alloreactivity of paired samples of adult and cord
      peripheral blood mononuclear cells, by measuring frequencies of both alloreactive
      T helper cells and cytotoxic T cell precursors (CTLp), using limiting dilution
      analysis. In addition we compared the phenotype of adult and neonatal PBMC, using
      monoclonal antibody staining. Cord PBMC in general showed higher frequencies of
      alloreactive Th than adult PBMC, with statistically significant differences in 6
      out of 10 experiments. There was no statistically significant difference between
      adult and cord CTLp frequencies. Adult and cord PBMC surface phenotype was
      similar, except that cord blood contained fewer lymphocyte function-associated-3
      (LFA-3) positive (memory) cells.

PMID- 1374947
TI  - FK506 as an agonist to induce inhibition of interleukin 2 production.

PMID- 1374949
TI  - Do humans see what monkeys see?

PMID- 1374950
TI  - Concanavalin A: a tool to change intracellular pH.

PMID- 1374948
TI  - The protective effect of FK506 pretreatment against renal ischemia/reperfusion
      injury in rats.
AB  - The effect of pretreatment with FK506 on renal ischemia and reperfusion (I/R)
      injury was investigated using a rat model. Animals were assigned to one of two
      groups (20 rats each). Group 1 animals (controls) received 0.5 ml saline while
      group 2 animals received FK506 (0.3 mg/kg), administered intravenously 24 hr
      prior to the induction of renal ischemia. A 60-min period of ischemia of the
      right kidney was induced, and upon reperfusion a left nephrectomy was performed.
      Blood samples for estimation of BUN, creatinine, and tumor necrosis factor were
      collected on days 0 (preischemia), 1, 2, 3, 5, 7, and 10 (postischemia). Rats
      were sacrificed after day 10 and renal tissue was examined histologically. All
      animals survived the ischemic episode. FK506 pretreatment significantly reduced
      the serum levels of BUN (P less than 0.02), creatinine (P less than 0.02), and
      TNF (P less than 0.05) as compared with that seen in controls. Histologically, at
      day 10, the kidneys showed the expected sequelae of prior renal I/R with various
      degrees of tubular damage. However, no objective differences were evident between
      the two groups. Based upon these data, it can be concluded that (1) FK506
      pretreatment ameliorates the functional renal injury associated with I/R, (2)
      renal ischemia induces the release of TNF, and (3) FK506 pretreatment results in
      a significant inhibition of TNF production. These data suggest that the release
      of TNF may be responsible for the increasing of BUN and creatinine levels seen
      after renal I/R and that pretreatment of renal donors with FK506 may improve
      renal function in the immediate post-transplant period.

PMID- 1374951
TI  - Cortical map plasticity in humans.

PMID- 1374952
TI  - Developmental and abnormal cell death in C. elegans.
AB  - Genetic analysis in Caenorhabditis elegans has identified several genes that
      function in normal developmental death as well as genes that can mutate to cause
      inappropriate cell death. The processes whereby some of these abnormal deaths
      occur depend on genes that participate in normal programmed cell death; others
      occur by an independent mechanism whereby mutation of members of a gene family
      leads to cell lysis. Molecular characterization of these 'death' genes in C.
      elegans is beginning to provide insight into the normal and aberrant mechanisms
      of cell death.

PMID- 1374953
TI  - Separate visual pathways for perception and action.
AB  - Accumulating neuropsychological, electrophysiological and behavioural evidence
      suggests that the neural substrates of visual perception may be quite distinct
      from those underlying the visual control of actions. In other words, the set of
      object descriptions that permit identification and recognition may be computed
      independently of the set of descriptions that allow an observer to shape the hand
      appropriately to pick up an object. We propose that the ventral stream of
      projections from the striate cortex to the inferotemporal cortex plays the major
      role in the perceptual identification of objects, while the dorsal stream
      projecting from the striate cortex to the posterior parietal region mediates the
      required sensorimotor transformations for visually guided actions directed at
      such objects.

PMID- 1374954
TI  - Control of neuronal excitability by corticosteroid hormones.
AB  - The rat adrenal hormone corticosterone can cross the blood-brain barrier and bind
      to two intracellular receptor populations in the brain--the mineralocorticoid and
      glucocorticoid receptors. Recent studies have revealed that the corticosteroid
      hormones are able to restore changes in neuronal membrane properties induced by
      current or neurotransmitters, probably through a genomic action. In general,
      mineralocorticoid receptors mediate steroid actions that enhance cellular
      excitability, whereas activated glucocorticoid receptors can suppress temporarily
      raised neuronal activity. The steroid-mediated control of excitability and the
      implications for information processing in the brain are reviewed in this
      article.

PMID- 1374955
TI  - Cortical representation of pain.

PMID- 1374956
TI  - Intrinsic neuronal determinants of regeneration.
AB  - Axon growth and axon regeneration are co-operative processes; the speed and
      extent of axon growth are influenced both by the properties of the environment
      surrounding the axon growth cone, and the properties of the neuron itself. In
      recent years, the environmental influences on axon growth have received most of
      the attention directed towards this area of research, but the properties of the
      neurons themselves are likely to be just as important. Within both adults and
      embryos there are differences in the growth potential of different neuronal
      types, and there is also evidence for an overall decrease in the vigour of axon
      growth with neuronal age.

PMID- 1374957
TI  - A consideration of neural counting methods.
AB  - It is often necessary to obtain unbiased estimates of neuronal or synaptic
      numbers. In the past, estimates were almost always done by counting profiles of
      these structures in single histological sections. Assumptions were then made and
      calculations were done to determine particle numbers or ratios. To the extent
      that the assumptions deviated from reality, the conclusions will be biased. That
      these biases are, in fact, serious has recently become apparent. To obtain
      unbiased particle counts, the presently available methods are serial-section
      reconstructions (which are accurate but cumbersome), and the recently developed
      disector method. The disector method, because it is unbiased and easy to use, is
      becoming the method of choice. The goals of this paper are to show why previous
      methods are biased and to describe the rationale behind the disector method so
      that neuroscientists can consider its appropriateness for their work.

PMID- 1374958
TI  - Cytokines and neurokines: related ligands and related receptors.

PMID- 1374959
TI  - Australian neuroscience: a background.

PMID- 1374960
TI  - Transmission at autonomic neuroeffector junctions.
AB  - For organs innervated by the autonomic nervous system, it is generally held that
      neuroeffector transmission is achieved by varicosities releasing transmitters
      some distance from the membranes of target cells. Transmitters are thought to
      diffuse through the extracellular space and interact with post-junctional
      receptors that are widely distributed over the cell membranes. This article
      presents an alternative view, suggesting that transmission can occur at organized
      neuroeffector contacts, that transmitters interact with restricted pools of
      specialized junctional receptors, and that many receptors on target cells are not
      involved in neuroeffector transmission.

PMID- 1374961
TI  - Activation and modulation of neuronal K+ channels by GABA.
AB  - Although the concept of GABAB receptors was introduced only ten years ago,
      several actions of GABAB agonists are already well established. They cause
      depression of transmitter release, a decrease in voltage-dependent Ca2+
      conductance and an increase in K+ conductance. It has recently been reported that
      GABA also changes the voltage dependence of the transient ('A' type) K+ channel.
      Depression of transmitter release by GABAB agonists may be caused by a decrease
      in Ca2+ conductance, an increase in K+ conductance or a modulation of A channels
      in presynaptic nerve terminals. Slow IPSPs in some neurons are generated by an
      increase in K+ conductance that can be blocked by GABAB antagonists and pertussis
      toxin. K+ channels of variable amplitude that are blocked by pertussis toxin are
      activated by GABAB agonists in cultured hippocampal neurons. Since arachidonic
      acid activates similar channels in excised patches of membrane, it may form part
      of a normal second messenger system linking GABAB receptors to K+ channels.

PMID- 1374962
TI  - Australian marsupials as models for the developing mammalian visual system.
AB  - This article makes two points. First, the diprotodont marsupials, including the
      kangaroos, wallabies and the Australian possum are not primitive mammals, and
      their brains make as good a general model of the higher mammals such as monkeys
      and humans as do those of the more common laboratory mammals such as cats and
      rats. Second, the peculiarities of marsupial reproduction, which comprises a very
      short period of intrauterine development, followed by a relatively protracted
      period of development in the pouch, provide unparalleled advantages for research
      into mammalian neuroembryology. Examples will be provided of how such research
      has made a contribution to our understanding of neural development, concentrating
      primarily on the visual system.

PMID- 1374963
TI  - Mechanical preprocessing in the mammalian cochlea.
AB  - The mammalian cochlea responds with exquisite sensitivity to the small
      fluctuations in air pressure that make up the stimulus of sound. Moreover, it
      responds to pressure fluctuations that occur extremely rapidly and that vary over
      a wide range of intensities--in both cases, to an extent outside the capabilities
      of unaided nerve fibres. Research performed during the past decade has shown that
      these properties are dependent on a physiological source of mechanical energy
      that operates probably within the outer hair cells of the organ of Corti. These
      cells, which are anatomically and functionally similar to the primary receptor
      cells, the inner hair cells, are believed to function as a source of mechanical
      power to assist the mechanical sensitivity of the cochlea, by mechanisms that
      currently are not understood. Several possible mechanisms have been proposed, but
      each has limitations that may make it an unsuitable candidate. Recent work has
      also demonstrated the likely role of mechanoelectrical transduction in outer hair
      cells in controlling the power source and thereby influencing the sensitivity and
      amplitude range of the cochlea.

PMID- 1374964
TI  - Kinaesthetic signals and muscle contraction.
AB  - Signals generated both peripherally and centrally contribute to the group of
      sensations termed kinaesthesia. Many experiments report sensations of position
      and movement under passive relaxed conditions without muscle contraction.
      However, kinaesthetic acuity is probably of greater functional value when
      subjects are active rather than passive and, accordingly, movement detection is
      markedly improved by muscular contraction. One mechanism contributing to this
      enhancement is likely to involve muscle spindle volleys. When identical
      microstimulation techniques are applied to skin, joint and muscle spindle endings
      innervating the hand, some cutaneous afferents and some joint afferents elicit a
      sensation, but activation of certain other cutaneous afferents and muscle spindle
      afferents rarely does. Activity in more than one muscle spindle afferent may be
      required for kinaesthetic sensations, whereas some single cutaneous and joint
      afferents may have a more 'secure' central projection.

PMID- 1374965
TI  - Roles of peptides in transmission in the enteric nervous system.
AB  - Studies of the enteric nervous system have proved to be important in the
      development of new concepts of the chemical nature of transmission from neurons.
      In particular, they have revealed the multiplicity of influences that peptides
      can have on transmission, such as their action as primary transmitters, and the
      fact that they often act as co-transmitters in enteric neurons. However, in other
      cases no roles can be attributed to neuropeptides in enteric neurons, and their
      involvement in short-term changes in excitability seems minor.

PMID- 1374966
TI  - Synaptic plasticity: on the trail of the retrograde messenger.

PMID- 1374967
TI  - Choline metabolism as a basis for the selective vulnerability of cholinergic
      neurons.
AB  - The unique propensity of cholinergic neurons to use choline for two purposes--ACh
      and membrane phosphatidylcholine synthesis--may contribute to their selective
      vulnerability in Alzheimer's disease and other cholinergic neurodegenerative
      disorders. When physiologically active, the neurons use free choline taken from
      the 'reservoir' in membrane phosphatidylcholine to synthesize ACh; this can lead
      to an actual decrease in the quantity of membrane per cell. Alzheimer's disease
      (but not Down's syndrome, or other neurodegenerative disorders) is associated
      with characteristic neurochemical lesions involving choline and ethanolamine:
      brain levels of these compounds are diminished, while those of
      glycerophosphocholine and glycerophosphoethanolamine (breakdown products of their
      respective membrane phosphatides) are increased, both in cholinergic and
      noncholinergic brain regions. Perhaps this metabolic disturbance and the tendency
      of cholinergic neurons to 'export' choline--in the form of ACh--underlie the
      selective vulnerability of the neurons. Resulting changes in membrane composition
      could abnormally expose intramembraneous proteins such as amyloid precursor
      protein to proteases.

PMID- 1374968
TI  - Axonal trees and cortical architecture.
AB  - In modern computer design considerable care is taken to arrange the components in
      such a way that wiring is kept to a minimum. Certain features of cortical
      structure--the mappings, stripes and blobs within areas, and areas themselves-
      are somewhat reminiscent of the layout of computer components, and suggest that
      the cortex may also be organized so as to economize on neuronal 'wiring'. One
      important difference between the brain and a computer is that the wiring in the
      brain takes the form of elaborate branched structures, namely axonal trees. In
      this article, it is argued that an assessment of the efficiency of cortical
      wiring must take account of the branching rules of these trees.

PMID- 1374969
TI  - Steady-state Ca2+ influx and electrical activity in endocrine cells.

PMID- 1374970
TI  - The pulvinar and visual salience.
AB  - One of the major problems of living in a rich visual environment is deciding
      which particular object or location should be chosen for complete processing or
      attention; that is, deciding which object is most salient at any particular time.
      The pulvinar has enlarged substantially during evolution, although little has
      previously been known about its function. Recent studies suggest that the
      pulvinar contains neurons that generate signals related to the salience of visual
      objects. This evidence includes: (1) anatomical and physiological observations of
      visual function; (2) augmented responses in the pulvinar for visual stimuli
      presented in important contexts; (3) suppression of activity for stimuli
      presented in irrelevant conditions; (4) thalamic modulation producing behavioral
      changes in cued attention paradigms; and (5) similar changes with visual
      distracter tasks.

PMID- 1374971
TI  - The neostriatal mosaic: multiple levels of compartmental organization.
AB  - The striatum, which is the major component of the basal ganglia, displays a
      complex mosaic organization of neurochemical systems that are related to its
      neuroanatomical connections. This mosaic organization reflects multiple levels of
      functional compartments. The first level is determined by the segregation of two
      major striatal output systems, one to the globus pallidus (external segment) and
      the other to the entopeduncular nucleus and substantia nigra. The second level
      segregates the cortical outputs of sublaminae of layer V between the patch and
      matrix compartments of the striatum, which project to the dopaminergic and
      GABAergic neurons in the substantia nigra, respectively. The third level is
      related to the topography of cortical inputs by which regions of the striatum may
      be functionally defined on the basis of the cortical areas with which they are
      connected. Neurochemical markers display complex mosaic patterns in the striatum
      that, when examined in the context of the multi-level compartmental organization
      of the striatum, reveal the highly organized manner by which the striatum
      processes cortical information.

PMID- 1374972
TI  - Dimorphic male brains and alternative reproductive tactics in a vocalizing fish.
AB  - Brains and types of behavior among sexually mature vertebrates are portrayed as
      having two phenotypic states: male and female. However, mating systems and the
      behavioral tactics employed by the two sexes are far more diverse than conveyed
      by this simple intersexual dichotomy. For example, in many species, sexually
      mature males may practice one of two alternative mating tactics. Recent studies
      of a sound-producing teleost fish now show that intrasexual dimorphism of vocal
      motor phenotypes among males accompanies the intrasexual divergence of types of
      reproductive behavior. Thus, one group of males, like females and juveniles,
      lacks the behavioral, neurophysiological and morphological traits typical of the
      sexually differentiated vocal motor pathway of the second group. The results are
      an explicit demonstration that for any one species: (1) alternative mating
      tactics can be paralleled by alternative phenotypes for the neurons that
      determine tactic-specific types of behavior, and (2) reproductive maturation is
      not obligatorily linked to the expression of neuronal secondary sex
      characteristics.

PMID- 1374973
TI  - Oxygen and acid chemoreception in the carotid body chemoreceptors.
AB  - The carotid bodies are arterial chemoreceptors that are sensitive to blood PO2,
      PCO2 and pH. They are the origin of reflexes that are crucial for maintaining
      PCO2 and pH in the internal milieu and for adjusting the O2 supply according to
      the metabolic needs of the organism in situations of increased demand, such as
      exercise and while breathing at decreased O2 partial pressures during ascent or
      when living at high altitude. Chemoreceptor cells of the carotid body transduce
      the blood-borne stimuli into a neurosecretory response that is dependent on
      external Ca2+. These cells have an O2-sensitive K+ current that is reversibly
      inhibited by low PO2. It is proposed that the depolarization produced by
      inhibition of this K+ current activates Ca2+ channels; Ca2+ influx and
      neurosecretion follow. The cells have also a potent Na(+)-Ca2+ antiporter that
      could be responsible for the intracellular Ca2+ rise required to trigger the
      release of neurotransmitters during high PCO2 or low pH stimulation.

PMID- 1374974
TI  - Further practical experiences in the recognition and management of carcinoma in
      situ of the testis.
AB  - 99 biopsies from the contralateral testis in patients with unilateral germ cell
      tumor were investigated using the semithin section technique. Four cases (4%)
      revealed a carcinoma in situ (CIS) pattern. Two patients underwent a local
      radiation (20 Gy), 2 patients received combination chemotherapy (cisplatin,
      etoposide and bleomycin; PEB). No tumor cells were found in control biopsies 4-8
      months after therapy. Both biopsy specimens taken from radiated patients lacked
      also germ cells. In contrast, 1 patient who was treated with PEB and also another
      1 presenting with a teratocarcinoma of apparently retroperitoneal origin and
      unilateral CIS revealed germ cells after chemotherapy. The present data suggest
      radiation therapy to be the first line treatment for CIS-bearing testes. In order
      to get informations about the distribution of CIS cells in the affected testes,
      one or two biopsies were additionally taken from macroscopically unsuspicious
      tissue surrounding various solid germ cell tumors (74 patients). 56 cases (76%)
      revealed CIS. Even considering the possibility of missing CIS, a screening biopsy
      is actually the only method for detecting early manifestations of germ cell
      tumors and should be performed routinely in contralateral testes of patients with
      germ cell tumors.

PMID- 1374975
TI  - Transplantation of human benign hyperplastic prostate tissue into nude mice:
      first results of systemic therapy.
AB  - Xenografts of human benign hyperplastic prostate tissue (BPH) have been
      established as a model for the investigation of the etiology of BPH. In this
      paper it is our aim to answer the question of whether this model is useful for
      the established therapy of the disease. Additionally we try to evaluate the value
      of a commonly used plant extract for the therapy of BPH. Is there any influence
      of the extract from Sabal serrulatum on the BPH tissue in our model? Human BPH
      tissue from 2 patients was transplanted into athymic nude mice and treated with
      three different regimens. Animals of group I did not receive any treatment and
      served as control, in groups II and III the tissue was stimulated by application
      of silicone tubes containing crystalline 5 alpha-dihydrotestosterone and
      estradiol. Animals of group II additionally were treated orally with the
      lipophilic extract of S. serrulatum (contained in Prostagutt N), which is
      commonly used for the treatment of BPH clinically. Significant inhibition of
      tissue growth was observed in group III when compared to group II. In group I
      (control) atrophy of the graft was observed as expected. However, histologically
      no differences were visible between groups II and III. Our experiment shows a
      significant growth-inhibiting effect of the plant extract for human BPH tissue in
      our model (p less than 0.05). We conclude that the nude mouse model can be useful
      for the evaluation of systemic therapy modalities of human BPH and that the plant
      extract may have a certain value for clinical treatment, which is not only due to
      subjective criteria.

PMID- 1374976
TI  - Prostate-specific antigen test: operating characteristics and assessment criteria
      in the diagnosis of prostatic cancer.
AB  - The sensitivity and specificity of prostate-specific antigen (PSA) in prostatic
      carcinoma is of considerable interest. In this study, we have assessed PSA and
      also correlations between positive and negative predictive values of PSA and the
      prevalence of prostatic cancer. Firstly, cutoff point must be selected as a
      positivity criterion for prostatic cancer, according to the purpose of the test.
      Besides sensitivity, all the other operating characteristics are dependent upon
      the prevalence of the disease. Specificity and positive predictive value increase
      while negative predictive value decreases when prevalence increases. As the
      relationship between the age and the prevalence of prostatic carcinoma is well
      known, the age of the patient becomes a variable of prominent importance when
      assessing the test.

PMID- 1374977
TI  - Serum prostatic acid phosphatase, gamma-seminoprotein and prostatic specific
      antigen in hemodialysis patients.
AB  - Serum concentrations of prostatic acid phosphatase (PAP), gamma-seminoprotein
      (gamma-Sm) and prostatic specific antigen (PSA) were measured in 31 hemodialysis
      patients without clinical signs of malignant disease. PAP, gamma-Sm and PSA
      levels in serum were not significantly different between control and hemodialysis
      groups. A significant reduction in these tumor markers was not found after
      dialysis treatment. This indicates that the measurement of PAP, gamma-Sm and PSA
      in serum is useful for the detection of prostatic cancer in patients undergoing
      hemodialysis.

PMID- 1374979
TI  - Alpha-fetoprotein-producing adenocarcinoma of the ureter.
AB  - We report a case of primary ureteral tumor producing alpha-fetoprotein (AFP).
      Computerized tomography, ultrasonography and endoscopy of the bile duct revealed
      no obvious tumor in the liver, gallbladder, bile duct, pancreas or ovary. Total
      nephroureterectomy was performed, and histopathological examination revealed
      adenocarcinoma of the ureter lined with transitional cell carcinoma in its base.
      The tumor was stained with immunohistological AFP stain, and the high serum AFP
      level normalized after resection of the tumor.

PMID- 1374978
TI  - Organisms in the prostate and antibiotics in the treatment of postoperative
      infections.
AB  - On 24 benign prostatic hyperplasia patients with preoperatively sterile urine,
      who also had no history of urinary tract infection, the organisms in the prostate
      obtained through transurethral resection as well as in the anterior urethra were
      isolated. In 17 patients out of 24, organisms obtained in the prostate were
      identical to those in the anterior urethra; therefore, it can be concluded that
      another 7 patients had organisms in the prostate itself before the operation.
      These results would suggest that sterile urine did not indicate sterile prostate
      and that organisms in the prostate did not always ascend from the urethra. In the
      patients who preoperatively received transurethral catheterizations,
      Streptococcus faecalis was the most predominantly isolated organism in the
      prostate, which was highly sensitive to ABPC and minocycline and lower to
      cephems. On the other hand, in the patients with no history of catheterizations,
      Staphylococcus epidermidis was the most commonly isolated one, which was highly
      sensitive to ABPC and minocycline as well as cephems. So, in the treatment of the
      cases with infectious symptoms after transurethral resection of the prostate,
      ABPC or minocycline should be selected as first-choice drugs rather than cephems.

PMID- 1374981
TI  - Biologically active cymbidium ringspot virus satellite RNA in transgenic plants
      suppresses accumulation of DI RNA.
AB  - A full-length DNA copy of cymbidium ringspot virus (CyRSV) satellite RNA was
      cloned downstream of the bacteriophage T7 RNA polymerase promoter. In vitro
      transcripts were biologically active in plants when coinoculated with the helper
      virus or its RNA. Although the transcripts contained 7 or 29 extra nucleotides at
      the 3' end, the proper 3' terminus was restored in the satRNA progeny. Full
      length cDNA clones of CyRSV satRNA under the control of the cauliflower mosaic
      virus 35S promoter and terminator were used to transform Nicotiana benthamiana
      plants. Integration of CyRSV satRNA sequence in the plant genome was tested by
      PCR amplification of DNA extracts from transformed plants and by detection of
      satRNA-related transcripts in total RNA extracts. Inoculation of transgenic
      plants with the helper virus induced replication of satRNA of the same size as
      the native molecule. Sequence analysis of the satRNA progeny showed that it was
      identical to natural CyRSV satRNA. Infected transgenic plants were not protected
      from apical necrosis and death by the presence of satRNA sequences. Rather,
      replication of satRNA was found to suppress accumulation of defective interfering
      RNA, which acts in the absence of satRNA as an attenuator of virus replication
      and disease.

PMID- 1374980
TI  - Biochemical characterization of an antigenic saline extract of Actinobacillus
      pleuropneumoniae serotype 5 and identification of a serotype-specific antigen for
      ELISA serodiagnosis.
AB  - A saline extract of boiled-formalinized whole cells from a local strain (81-750;
      Quebec, Canada) of Actinobacillus pleuropneumoniae, serotype 5b was used as an
      antigen in an enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of
      swine pleuropneumonia. Characterization of this crude extract was done and
      proteins, neutral sugars, hexosamines, and 2-keto-3-deoxyoctonate (KDO) were
      evaluated. On phenol extraction of the crude extract a serotype-specific antigen
      of polysaccharidic nature was recovered from the aqueous phase. This antigen was
      characterized using sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE) with Coomassie blue, silver and Schiff stainings. Immunoblots were
      done using sera of experimentally infected pigs that showed serotype specificity
      and cross-reactivity. Overall, the results indicate that the O-chain of
      lipopolysaccharides is a specific antigen that could be used in ELISA for the
      serodiagnosis of serotype 5 of A. pleuropneumoniae.

PMID- 1374982
TI  - Epitopic mapping of linear and conformation-dependent antigenic determinants on
      GP5 of five U.S. bluetongue viruses.
AB  - Two distinct antigenic determinants of the major outer capsid protein, GP5, of
      five U.S. bluetongue viruses have been identified and mapped using monoclonal and
      oligoclonal antibodies. One antigenic site, identified by oligoclonal antibody AK
      15, was found to be common and conserved in all five U.S. BTV serotypes. This
      linear epitope was located between amino acid residues 175 and 189
      (ALQREAAERSEDEIK). The second determinant identified by monoclonal antibody 34.7
      was present in BTV-2, -10, -11, and -17 but absent in BTV-13. The binding of this
      monoclonal antibody to GP5 could be blocked specifically by one of three short
      synthetic peptides located among amino acid residues 33-42 (KAAERFAESE), 159-168
      (EKILKEEDSK), and 206-215 (EIERDGMQEE), indicating that this antigenic
      determinant is conformation-dependent. Oligoclonal antibody (AK-15) reacted with
      denatured GP5 immobilized on nitrocellulose membrane after Western transfer as
      well as with native GP5 present on the surface of purified BTV virions.
      Monoclonal antibody (34.7) reacted only with denatured GP5 but not native GP5
      using an ELISA assay. However, these two antigenic epitopes alone did not elicit
      detectable neutralizing antibodies as determined by plaque reduction assay.

PMID- 1374983
TI  - Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy
      seropositives as well as in patients with tropical spastic paraparesis.
AB  - In human T cell lymphoma/leukemia virus (HTLV-1)-infected people with tropical
      spastic paraparesis (TSP), there are activated HTLV-1-specific cytotoxic T
      lymphocytes (CTL) in the circulation and lymphocytic infiltrates in spinal cord
      lesions that are rich in CD8+ T cells. These observations suggest a role for
      virus-specific CTL in the pathogenesis of TSP. We have examined the anti-HTLV-1
      cytotoxic activity of freshly isolated CD8+ T cells from peripheral blood
      lymphocytes of eight subjects seropositive for HTLV-1. Four of five subjects with
      TSP had circulating activated anti-Tax CTL. However, two of three seropositive
      subjects without TSP also had activated anti-Tax CTL. These observations show
      that such activated CTL are not confined to patients with TSP and raise some
      uncertainty about their significance in the pathogenesis of the disease. In
      cultures of CD8+ T cells from two TSP subjects, we detected CTL with other HTLV-1
      specificities, without exogenous antigenic stimulation. A CTL epitope in the
      middle region of Tax and one in the C terminus of Pol have been mapped at the
      peptide level and the HLA Class 1 molecules restricting their recognition have
      been defined.

PMID- 1374984
TI  - Isolation and characterization of a retrovirus from the fish genus Xiphophorus.
AB  - A cell line (BsT) established from neoplastic embryonal tissues of the platyfish
      (Xiphophorus maculatus) released spontaneously retrovirus-like particles. The
      particles have a buoyant density of 1.16 g/ml, a mean diameter of 100 nm and the
      morphology of immature retroviruses. The particle-associated proteins p70, p65,
      and p28 react with an antiserum directed against the major internal feline
      leukemia virus structural protein p27. The particles are associated with a
      reverse transcriptase. The purified enzyme has a molecular weight of about 70 kDa
      and prefers the template primers poly(rA):oligo(dT), poly(dC):oligo(dG), and
      poly(rC):oligo(dG) in the presence of Mn2+. The enzyme activity is inhibited by
      antibodies directed against the reverse transcriptase of feline leukemia virus
      and simian sarcoma virus. The particles contain a ribonucleic acid of about 70 S.
      In an endogenous reverse transcriptase reaction nucleic acids in the range of 0.2
      to 0.4 kb were synthesized. In Northern blots with these nucleic acids as probe,
      three transcripts of about 8.5, 4.2, and 1.5 kb were detected in BsT cells.
      Southern blot analysis with the same probe demonstrates related sequences in the
      DNA of BsT cells and the platyfish and swordtail (Xiphophorus helleri).
      Hybridization experiments with the LTR-gag region of the feline leukemia virus
      show homologous sequences in the Xiphophorus genome.

PMID- 1374985
TI  - Influenza viruses differ in recognition of 4-O-acetyl substitution of sialic acid
      receptor determinant.
AB  - Equine alpha 2-macroglobulin (EM), known to contain both Neu5Ac and Neu4,5Ac2
      sialic acid residues, was treated with Vibrio cholerae sialidase for the
      selective removal of Neu5Ac and was compared with the untreated EM for its
      binding by a panel of influenza viruses. Type A H3N2 virus strains having Leu in
      position 226 of their hemagglutinin (HA) changed the affinity for sialidase
      treated EM only slightly, if at all, indicative of their ability to bind the 4-O
      Ac-substituted Neu5Ac receptor determinant. At the same time, all B and H1N1
      viruses, some H2N2 variants, as well as H3N2 strains with 226 Gln studied were
      unable to recognize Neu4,5Ac2 moieties of EM. Molecular modeling based on the
      known 3-D structure of H3 HA complexed with sialyllactose (Weis et al. (1988)
      Nature 333, 426-431) predicts that the 4-O-Ac substituent of sialic acid would
      protrude with its carbonyl oxygen inside the receptor-binding site of HA, thus
      possibly interfering with binding.

PMID- 1374986
TI  - Resistance of human immunodeficiency virus type 1 reverse transcriptase to TIBO
      derivatives induced by site-directed mutagenesis.
AB  - The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is
      the target enzyme for the tetrahydro-imidazo[4,5,1-jk][1,4]- benzodiazepin
      2(1H)one and thione (TIBO) derivatives, a class of highly potent and selective
      anti-HIV agents that specifically inhibit HIV-1 but not HIV-2 replication. The
      amino acid sequence divergence may be held responsible for the differential
      sensitivity of HIV-1 RT and HIV-2 RT to the TIBO derivatives. Using site-directed
      mutagenesis, we have introduced several amino acid substitutions in the conserved
      regions of HIV-1 RT. Where applicable, the amino acids were replaced by the
      corresponding amino acids present in HIV-2 RT. The amino acid residues Y181 and
      Y188 appeared to be critical for the anti-HIV-1 RT activity of the TIBO
      derivatives, since substitution of these residues by the corresponding HIV-2
      amino acids I181 and L188 resulted in a virtual loss of TIBO sensitivity without
      loss of enzymatic activity.

PMID- 1374987
TI  - [Reactive arthritis: pathogenesis, diagnosis and therapy].

PMID- 1374988
TI  - Intake of intense sweeteners in Germany.
AB  - The dietary intake of aspartame, cyclamate, and saccharin was evaluated in
      Germany (FRG) in 1988/89. In the first part of the study the sweetener intake was
      evaluated in a representative sample of the population. Complete 24-h records of
      the amount and type of all foods and drinks consumed were obtained from 2,291
      individuals. The total daily intake was calculated for each person from the
      sweetener content of each product and was expressed in mg/kg body weight (bw).
      35.9% of the participants ingested one or more sweeteners on the examination day.
      Cyclamate and saccharin were the prominent sweeteners because aspartame was at
      that time permitted only under special regulatory exemption, and products
      containing acesulfame were not yet available. For users of intense sweeteners the
      mean intakes of aspartame, cyclamate, and saccharin were 0.15, 2.62, and 0.250
      mg/kg bw/day, respectively. At the 90th percentile of intake, i.e., for the heavy
      consumer, the ingestion of cyclamate and saccharin was about 2.5 times higher.
      Persons who adhered to a diet (diabetes, weight control) did not ingest
      sweeteners in substantially higher amounts. Tabletop sweeteners and beverages
      were the most important sources of sweeteners, and they contributed more than 80%
      of the total intake. Consumption of sweeteners in excess of the Acceptable Daily
      Intake (ADI) was rarely observed (saccharin: one person, cyclamate: 16 persons).
      In the second part of the study, the sweetener intake was further evaluated
      during a 7-day period in those subjects who in the 1-day study ingested any of
      the sweeteners in excess of 75% of the ADI. Complete 7-day food records were
      available from 40 out of the 41 subjects who fulfilled this criterium. In this
      selected subgroup in which 19 subjects were less than 19 years old, the mean
      daily intakes of aspartame, cyclamate, and saccharin were 0.13, 4.53, and 0.42
      mg/kg body weight (bw), respectively. These levels correspond to 0.33, 41 and 17%
      of the corresponding ADI values. No subject exceeded the ADI of aspartame or
      saccharin on any day of the study. For cyclamate, the mean daily intake over the
      7-day period exceeded the ADI in 4 subjects. The results indicate that at the
      time of the study the then valid German sweetener regulation protected the
      consumer adequately, and that the sweetener intake was in 99.8% of all examined
      persons within recommended limits.

PMID- 1374989
TI  - [A child with XYY syndrome as experienced by his mother. A report of daily
      journal recordings].
AB  - A mother's experiencing of the development of her son with "XYY syndrome" is
      presented based on notes from the mother's diary. According to recent findings in
      unselected longitudinal studies the boy clearly belonged to a subgroup of the
      more severely affected children. His developmental language and motor delays,
      other language problems and problems at school were typical, whereas his slightly
      reduced IQ, in the lower normal range, and aggressive and autistic symptoms were
      atypical. In many ways the mother's experience is comparable to that of parents
      of mentally retarded children. Complicating factors were the inconspicuous
      phenotype, late diagnosis and lack of professional help. It is shown that
      parental adaptation to a "handicapped" child can occur in phases. These can be
      understood through models of mourning or coping. It would be of great help to
      these families if self-help groups would be established.

PMID- 1374990
TI  - Embedding of dithranol in lipid crystals.
AB  - A new cream base, based on lipid crystals, was used to formulate an antipsoriatic
      cream containing Dithranol. The cream consists of solid lipid crystals of C12 and
      C14 monoglycerides. The lipids are solid at room temperature but melt at skin
      temperature. The cream is easy to wash off, provides good stability of dithranol,
      and is practically nonstaining.

PMID- 1374991
TI  - Argyrophilic proteins of the nucleolar organizer region in acute leukemias and
      its relation to the S-phase fraction of leukemic cells.
AB  - Nucleolar organizer regions (NORs) are loops of DNA which transcribes to
      ribosomal RNA. The NOR-related protein becomes visible in nucleus by a silver
      staining technique under a light microscope, and it has been named argyrophilic
      protein of NOR (Ag-NOR). In various malignancies, the correlation between the
      proliferation potential of tumor cells or histological grade and the number of Ag
      NORs has been reported. In this study, we investigated the Ag-NOR of acute
      leukemic cells and its relation to the in vivo proportion of bone marrow leukemic
      cells in DNA synthetic phase. The number of Ag-NORs in bone marrow leukemic cells
      was more than that in peripheral blood (means values 2.78 and 2.48, respectively,
      p less than 0.01). This result shows that the number of Ag-NORs reflects the
      vigorous proliferative potential of bone marrow leukemic cells. However, no
      significant correlation was obtained between the number of Ag-NORs and the
      bromodeoxyuridine-labeling indices (r = 0.2064). These results suggest that Ag
      NOR might be one of the markers for cellular proliferation in leukemia, while DNA
      synthesis of leukemic cells do not seem to be directly related to Ag-NOR. In
      order to clarify the role of Ag-NOR in leukemia, further studies are needed.

PMID- 1374992
TI  - Interleukin-6 reduces the optimal growth in vitro of leukemic blast progenitors
      from acute myeloblastic leukemia patients.
AB  - The combined effects of five cytokines; recombinant human (rHu) granulocyte
      colony-stimulating factor (G-CSF), rHu granulocyte-macrophage colony-stimulating
      factor (GM-CSF), rHu interleukin-1 beta (IL-1 beta), rHu interleukin-3 (IL-3),
      and rHu interleukin-6 (IL-6) on blast colony formation in methylcellulose by
      leukemic blast progenitors from 10 patients with acute myeloblastic leukemia
      (AML) were studied. Combination of G-CSF, GM-CSF, IL-1 beta, and IL-3 stimulated
      maximum blast colony formation in 9 patients. Further addition of IL-6 reduced
      the combined effect of the four cytokines on blast colony formation. IL-6
      regulates the proliferation of leukemic blast progenitors and may play an
      important role in the regulation of hematopoiesis.

PMID- 1374993
TI  - Localization of prostatic glycoconjugates by the lectin-gold method.
AB  - The glycoconjugates of the lateral prostate were examined ultrastructurally by
      lectin-gold histochemistry in combination with a low-temperature embedding
      technique using Lowicryl K4M. The binding patterns of concanavalin A, wheat germ
      agglutinin, Griffonia simplicifolia, soybean agglutinin, peanut agglutinin,
      Ricinus communis agglutinin isolectin I, Griffonia simplicifolia isolectin B4,
      Ulex europaeus isolectin I and Phaseolus vulgaris agglutinin P have been
      documented in the subcellular compartments of the lateral prostate. The results
      show that the granular endoplasmic reticulum (GER) is rich in glycoproteins with
      mannosyl residues while the Golgi cisternae, secretory granules and microvilli
      are less so. The mannose (Man) and N-acetylglucosamine (GlcNAc) residues present
      in the GER of the epithelial cells may be associated with the initial assembly of
      the N-linked oligosaccharides of glycoproteins. The secretory granules exhibited
      different reactivities to lectins. Most of the lectin-binding sites confined to
      the limiting membranes may play a role in the transport of plasmalemma
      glycoconjugates to the apical plasma membrane. The epithelial Golgi stack is rich
      in GlcNAc, galactose (Gal), N-acetylgalactosamine (GalNAc) and sialic acid
      residues, and a compartmental organization of the Golgi stack is apparent which
      might be associated with the sequential addition of sugar residues to the
      oligosaccharides. The plasma membrane contains abundant Man, GlcNAc, Gal, GalNAc
      and complex carbohydrates, especially in the microvilli, and a differential
      lectin labelling was noted between the apical and basolateral plasma membrane.
      The present study showed that fucose-containing glycoconjugates were detected in
      the apical plasma membrane of the lateral prostate. The stromal extracellular
      matrices as well as the epithelial basement membranes demonstrated weak lectin
      reaction. Man, GlcNAc, Gal residues and complex sugars were also noted in the
      stromal tissues of the lateral prostate including the extracellular matrix,
      capillaries and smooth muscle.

PMID- 1374994
TI  - Solid cell nests of the thyroid gland. Optic and immunohistochemical study at
      autopsies.
AB  - In order to establish the prevalence of solid cell nests (SCN) in adult thyroids,
      we studied 100 consecutive glands at necropsy. These were serially sectioned and
      stained with routine and immunoperoxidase techniques in order to detect
      calcitonin, carcinoembryonic antigen, thyroglobulin and keratin. SCN may be
      considered as normal thyroid gland components, and they share with C cells a
      common origin in the ultimobranchial body.

PMID- 1374995
TI  - Social inhibition and motor skill performance in first, third and fifth grade
      children.
AB  - A systematic literature search over a period of 7 years yielded 28 articles about
      social inhibition with few of them addressing the relationship between social and
      motor functioning. Two sets of empirical data are reported. Firstly, a
      replication of the study performed by Zimmer in 1981 on the relationship between
      social inhibition and motor skill performance has been carried out with first,
      third and fifth grade children. Contrary to Zimmer's (1981) earlier findings with
      pre-school children, no relationship was found between motor skills test and
      social inhibition at any of the three age levels studied. Secondly, a group of
      children who attended extra physical education classes because of delay in motor
      performance (called "motoric remedial teaching") was found to score significantly
      lower on the motor skills test and higher on the social inhibition scale than a
      matched group of classmates. These findings indicate that although social
      inhibition appears not to be related to motor skill performance in the normal
      population, a significant relationship is present in a special sample of
      motorically delayed children.

PMID- 1374996
TI  - Early symptoms in autism from family home movies. Evaluation and comparison
      between 1st and 2nd year of life using I.B.S.E. scale.
AB  - The analysis of 11 home movies taken by parents before the recognition of
      autistic or atypical disorders of their own child has confirmed the major value
      of this method for describing early pathological signs. Symptomatology analysis
      has revealed anomalies of eye contact, a deficiency and variability of emotional
      expression, a defect of attention and initiation of communication, as well as
      motor abnormalities. The comparison of the frequency of abnormal behaviour,
      assessed with a rating scale among three groups of children (autistic, pervasive
      developmental disorders and normal) revealed behavioural differences as a
      function of early age and diagnosis, which concern not only social and
      communicative behaviours, but those of emotion and attention as well. The limits
      and interest of this methodological approach are discussed and the possibilities
      of subsequently using these documents in a more complete method, such as blind
      examination and scoring by uninformed investigators, are suggested.

PMID- 1374997
TI  - Galanin receptors and their second messengers in the lumbar dorsal spinal cord.
AB  - The ligand binding properties of galanin receptors were examined in crude
      synaptosomal fraction preparations of lumbar dorsal spinal cord, using chloramin
      T mono-iodinated porcine Tyr26 galanin as ligand. The equilibrium binding of
      [125I]galanin showed the presence of a single population of high-affinity binding
      sites with KD = 0.6 +/- 0.2 nM in a concentration of 55 +/- 15 fmol mg-1 protein
      (Bmax). The N-terminal fragments galanin (1-16) and galanin (1-12) fully
      displaced specific [125I]galanin binding from membranes with IC50 values 6 nM and
      4 microM, respectively. The C-terminal fragment galanin (17-29) did not displace
      [125I]galanin when applied in the concentration range 10(-11)-10(-4) M. GTP
      inhibited the specific binding of [125I] galanin in a concentration dependent
      manner, with 54% inhibition at 1 mM, suggesting that the galanin receptor found
      in lumbar dorsal spinal cord is G-protein coupled. Second messenger systems,
      through which the galanin receptor in lumbar dorsal spinal cord may exert its
      effect, were also studied. A galanin (10 microM) produced inhibition (58%) of the
      depolarization induced cGMP increase was found, whereas galanin (10 microM) did
      not inhibit the noradrenalin (100 microM) activated cAMP synthesis or
      phosphoinositide turnover in tissue slices of the spinal cord. Bilateral
      transection of the sciatic nerve at midthigh level 14 days prior to the binding
      experiment was performed, a treatment which is known to cause a dramatic increase
      of galanin-like immunoreactivity in the superficial layers of the dorsal spinal
      cord, dorsal root ganglion and in galanin mRNA levels, but no significant effect
      on Bmax or KD of the galanin receptor was found.

PMID- 1374998
TI  - Effects of age and streptozotocin-induced diabetes on contents and effects of
      substance P and vasoactive intestinal polypeptide in the lower urinary tract of
      the rat.
AB  - The urinary bladder and urethral content of substance P and vasoactive intestinal
      polypeptide and the in vitro effects of the peptides on the bladder were studied
      at 6 weeks and 6 months of streptozotocin-induced diabetes in the rat. The
      results were compared with those obtained in age-matched control animals. Both
      short-term and long-term streptozotocin treatment induced a clearcut increase in
      bladder weight. Bladder substance P content was increased in both groups of
      diabetic animals but substance P concentration was similar in control and
      diabetic animals. Vasoactive intestinal polypeptide content was slightly higher
      in diabetic animals than in controls but vasoactive intestinal polypeptide
      concentration was significantly lower in the bladders from both short-term and
      long-term diabetic animals. The bladder contractile response to substance P was
      similar in all groups of animals and vasoactive intestinal polypeptide was found
      to be devoid of contractile or relaxatory effects in the rat bladder. No change
      in urethral weight was seen with diabetes. There were no clear-cut changes in the
      urethral contents or concentrations of substance P and vasoactive intestinal
      polypeptide. The study also enabled comparisons between younger (3 months) and
      older (9 months) rats. This comparison showed a decrease in the concentrations
      and contents of substance P and vasoactive intestinal polypeptide between young
      and older rats. The changes were seen in both the bladder and the urethra and
      were similar in diabetic and normal animals.

PMID- 1374999
TI  - Prevention of carryover contamination in the detection of beta S and beta C genes
      by polymerase chain reaction.
AB  - As the polymerase chain reaction (PCR) process becomes a common tool in genetic
      diagnostic laboratories, prevention of carryover contamination from previous PCR
      amplifications has become an urgent topic. A PCR carryover prevention technique,
      utilizing deoxyuridine triphosphate (dUTP) and uracil DNA glycosylase (UDG), has
      been described recently. We report on its adaptation to a diagnostic system for
      detecting hemoglobin SS and SC diseases. Excellent amplification was achieved by
      increasing the dUTP and MgCl2 concentrations. dU-containing DNA could be analyzed
      by restriction endonucleases to distinguish the beta S from beta A gene using
      Ddel, but two other restriction enzymes, Bsu361 (replacement for MstII by the
      manufacturer) and CvnI, can no longer be used. The dU-containing PCR products
      retained their hybridization specificity with allele-specific oligonucleotide
      (ASO) probes for the beta A, beta S, and beta C genes. The PCR carryover
      prevention technique is easy to use and takes only 20 additional minutes. It
      should be extremely useful to genetic diagnostic laboratories where PCR is
      repeated daily and carryover contamination may thus lead to misdiagnoses.

PMID- 1375000
TI  - Leukemic proliferation of myeloblasts after granulocyte colony-stimulating factor
      administration following lymphoma-type chemotherapy in a patient with uterine
      cervical myeloblastoma.

PMID- 1375001
TI  - Clinical relevance of immunological dissection in T-ALL: a report on 20 cases
      with stem cell (CD7+, CD4-, CD8-, CD1-) phenotype.
AB  - In a prospective study on 44 cases of T-cell origin acute lymphoblastic leukemia,
      20 patients were found to display an immature immunophenotype (CD7+, CD4-, CD8-,
      CD1-) and were classified as T-stem cell leukemia (T-SCL). Twenty-four patients
      expressed CD4 and/or CD8 antigens on their blast cells, designated T acute
      lymphoblastic leukemia (T-ALL). The T-SCL subset showed a significantly higher
      median age, a more frequent incidence of extramedullary leukemia, a morphology L1
      in most cases, and a poor response to treatment in terms of either complete
      remission rate or median survival duration. In addition, significant differences
      between the two groups were found in evaluating the number of days of blast
      disappearance from peripheral blood, of CR achievement, and of neutrophils and
      platelets recovery. We conclude that T-SCL represents a distinct clinical entity,
      characterized by a poor response to ALL conventional chemotherapy. Alternative
      therapeutic approaches should be developed for patients suffering from this form
      of leukemia, to modify its severe prognosis.

PMID- 1375002
TI  - Postmarketing surveillance study of permethrin creme rinse.
AB  - BACKGROUND: An observational, epidemiological study was undertaken to evaluate
      the safety of permethrin 1% creme rinse (Nix) for treatment of head lice
      infestations. METHODS: Thirty-seven local public health departments enrolled a
      total of 38,160 patients for 47,578 treatments with permethrin or other
      pediculicides from September 1, 1986, through January 31, 1988. Follow-up safety
      information was collected between 7 and 14 days following treatment via return
      visit or telephone contact. RESULTS: One hundred three adverse events were
      reported among 41,955 evaluable treatments. The rates of reported adverse events
      were 2.2 per 1000 treatments among permethrin treatments, 3.4 per 1000 treatments
      among lindane treatments, and 1.5 per 1000 treatments among other over-the
      counter treatments. No serious, unexpected adverse events were detected in the
      18,950 patients treated with permethrin. CONCLUSIONS: This study confirmed the
      safety profile of permethrin in conditions of general use, as seen in clinical
      trials. Postmarketing safety monitoring in public health departments of drugs
      used to treat public health conditions was shown to be feasible.

PMID- 1375003
TI  - The Montgomery T-tube in terminal care.
AB  - PURPOSE: The use of a Montgomery T-tube as a palliative measure in the treatment
      of patients with respiratory obstruction due to cancer is described. PATIENTS AND
      METHOD: Six patients with terminal malignant disease presented with airway
      obstruction caused by direct infiltration of the trachea by tumor. The primary
      carcinoma originated in the esophagus in five cases, whereas one patient had
      metastatic carcinoma of the breast. In each case, the airway was initially
      secured using a rigid ventilating bronchoscope that was advanced past the area of
      tracheal obstruction. Tumor was removed from the lumen of the bronchoscope with
      suction and cup forceps. Anesthesia was continued through the bronchoscope while
      the trachea was exposed through a cervical incision and a window cut in the
      anterior tracheal wall. A Montgomery T-tube was inserted as the bronchoscope was
      withdrawn. RESULTS: This technique allowed dramatic relief of airway obstruction
      in all cases. The tube relieves the obstruction by stenting the airway and
      permits speech in most patients. The authors stress the need for frank discussion
      with patients and family when considering the appropriateness for this form of
      palliation.

PMID- 1375004
TI  - Evaluation of the allergenicity of infant formulas in a guinea pig model.
AB  - In the present study we evaluated the allergenicity of infant formulas using a
      guinea pig model. Seven groups of ten guinea pigs each maintained on a diet free
      of cow milk received either water or pasteurized cow milk (PCM) or a conventional
      cow milk infant formula (CMF) or whey hydrolysate formula (WHF) to drink. On day
      37 all the animals were challenged by intravenous injection with 0.5 mL of
      supernatant of either PCM or WHF. The reactions to the challenge were expressed
      as none, mild, severe nonfatal, and fatal. A score ranging from 0 to 3 was
      assigned to each animal and considered in the statistical analysis; P values are
      expressed as comparisons to the negative water-fed control group. Animals fed WHF
      and challenged with WHF (group 1), showed 10% fatal reactions and 50% severe but
      not fatal reactions (P less than .05). When challenged with PCM (group 2), 40%
      showed a mild reaction. Cow milk formula-fed animals showed 10% fatal reactions
      and 70% severe reactions when challenged with WHF (group 3). The same challenge
      caused 40% severe reactions in animals fed PCM (group 4) (P greater than .05).
      Animals fed and challenged with PCM (group 5) showed 100% fatal reaction (P less
      than .01). Animals fed water showed no reaction when challenged with either WHF
      (group 6) or PCM (group 7). The results suggest that WHF has less anaphylactic
      sensitizing power than PCM and CMF.

PMID- 1375006
TI  - Inflammatory cells and mediator release during ragweed challenge: correlation
      between histamine content in nasal secretions and appearance of inflammatory
      cells.
AB  - The early and late phase responses in the nasal tissues exhibit release of
      inflammatory mediators and a mixed cellular influx in separate nasal challenges.
      To explore this phenomenon further, histamine concentration was determined along
      with characterization of cell influx during dose-dependent ragweed challenges.
      Ten subjects with allergic rhinitis underwent two unilateral nasal lavages using
      incremental 3-fold concentrations of short ragweed. Low doses of ragweed (0.016
      to 0.114 units Amb a I) rarely induced cell influx (1/18 challenges), whereas
      moderate doses (0.432 to 1.3 units Amb a I) caused cell influxes in 7/18 and high
      doses (3.39 to 11.7 units Amb a I) resulted in cell influxes in 8/17. The eluent
      contained greater than 50% neutrophils in seven challenges; greater than 50%
      eosinophils in three; and a mixed pattern in six. There was a significant
      association between the dose of antigen and the level of histamine. Challenges
      with an eosinophilic influx tended to be associated with higher concentrations of
      histamine than neutrophilic influxes. Similar to the immediate skin response, the
      early allergic response in the nose demonstrated a cell influx with release of
      histamine. Nasal cellular inflammation therefore can occur within minutes of
      allergen exposure.

PMID- 1375007
TI  - Characterization of a feline T-cell-specific monoclonal antibody reactive with a
      CD5-like molecule.
AB  - The 43 monoclonal antibody raised against feline T cells was found to react with
      a single-chain glycoprotein of Mr 72,000 that is present on most thymocytes, 60%
      of lymph node cells, 20% of splenocytes, and 45% of blood mononuclear cells. All
      CD4+ and CD8+ T cells were found to express the 43-reactive determinant, as did a
      small subpopulation of CD4-/CD8-/IgM- lymphocytes in the periphery. The 43
      reactive determinant was not detected on B cells, macrophages, or other types of
      blood cells. The 43 antigen was phosphorylated in resting and activated T cells.
      Its expression was upregulated by stimulation with phorbol myristate acetate and
      with phytohemagglutinin. When added to concanavalin A-stimulated T-cell cultures
      in low concentrations, the 43 antibody was found to augment mitogenesis. The data
      indicate that this antibody may identify a CD5 homologue on feline T cells.

PMID- 1375005
TI  - Use of Tranilast [N-(3,4-dimethoxycinnamoyl) anthranilic acid] in secretory
      otitis media.
AB  - Treatment with Tranilast of 45 patients (87 ears) with secretory otitis media was
      studied. Tranilast was administered orally for at least 1 month. The evaluation
      of its effectiveness was based on changes in subjective symptoms, tympanic
      membrane findings, hearing level, and tympanometry. Subjects were divided into
      three groups: allergy group (group I), nonallergy group (group II) and deformity
      disorder group (group III). The respective percentages of Tranilast efficacy for
      these three groups were 46.2%, 42.1%, and 10.0%, respectively. Equivalent
      effectiveness was demonstrated whether or not allergies were present. After
      Tranilast administration, the drug and its metabolites were found in MEE samples
      from all the patients. Anaphylatoxin (C3a, C5a) activities in the MEE were shown
      to decrease gradually after Tranilast administration. Tranilast may be effective
      for treating secretory otitis media because it directly suppresses anaphylatoxin
      present in middle ear effusion.

PMID- 1375008
TI  - Granulocyte colony-stimulating factor does not enhance endotoxin-induced acute
      lung injury in guinea pigs.
AB  - We studied recombinant human granulocyte colony-stimulating factor (G-CSF) in
      terms of its hematopoietic and neutrophil-activating effects on acute lung injury
      induced by endotoxin. Guinea pigs were divided into four groups: (1) saline
      control animals, (2) endotoxin alone, (3) cyclophosphamide (CPA)+endotoxin, and
      (4) G-CSF+endotoxin. A G-CSF dose of 20 micrograms/kg was given subcutaneously
      twice a day for 5 days. Animals were observed for 4 h after intravenously
      administered endotoxin (0.02 and 2.0 mg/kg) with serial measurements of complete
      blood counts and hemodynamics. Lung extravascular water, [125I]albumin leakage in
      lung tissue, and histopathologic features were examined at death. The endotoxin
      alone group showed peripheral leukopenia, transient hypotension, excess lung
      water, increased albumin leakage, PMN accumulation in lung tissue, and gross
      histopathologic edema. G-CSF-treated animals showed attenuated responses in
      peripheral leukopenia, excess lung water, and albumin leakage in comparison with
      the endotoxin-alone group. No augmented responses were seen in the G-CSF group.
      The CPA+endotoxin group also had attenuated lung injury, which was similar to
      that in the G-CSF group. In conclusion, pretreatment with G-CSF tended to
      attenuate rather than enhance neutrophil-dependent acute lung responses to
      endotoxin.

PMID- 1375009
TI  - Isolated bronchi from asthmatics are hyperresponsive to adenosine, which
      apparently acts indirectly by liberation of leukotrienes and histamine.
AB  - Bronchial hyperresponsiveness can be demonstrated in asthmatic subjects by
      inhalation of adenosine, but the action of adenosine at the level of the human
      airway smooth muscle has received comparatively little attention. We have
      previously observed that bronchi isolated from one asthmatic patient contracted
      in response to adenosine. We have therefore, during the course of a 3-yr study,
      further characterized the effects of adenosine in bronchi prepared from surgical
      specimens of lung tissue of asthmatics and of nonasthmatics. Contraction
      responses were always studied in vitro the same day the tissues were obtained.
      Bronchi from asthmatics (19 strips from six patients) were more sensitive to
      adenosine than were bronchi from nonasthmatics (21 strips, seven patients). In
      contrast, there was no difference in sensitivity to histamine or leukotriene C4
      between the two groups, nor was the maximal tissue contractility different. The
      contractile effect of adenosine was inhibited by the adenosine A1-antagonist 2
      thio-[(1,3-dipropyl)-8-cyclopentyl]-xanthine as well as by the dual A1 and A2
      antagonists 8-(p-sulfo)-phenyltheophylline and theophylline. The combination of
      leukotriene antagonism (receptor-antagonist ICI 198,615 or biosynthesis inhibitor
      MK-886) and histamine antagonism (antihistamines mepyramine and metiamide)
      blocked the contractile effects of adenosine, suggesting that adenosine acts
      indirectly by liberation of leukotrienes and histamine, possibly from mast cells.
      The findings of increased sensitivity to adenosine in bronchi from asthmatics to
      our knowledge represents the first evidence of increased bronchial reactivity in
      vitro in asthmatics.

PMID- 1375010
TI  - CD5-negative cell mediated experimental hypersensitivity pneumonitis.
AB  - Experimental hypersensitivity pneumonitis (EHP) can be transferred to Strain 2
      guinea pigs by peripheral lymph node (PLN) cells cultured in vitro with antigen.
      The phenotype of the active cells has not been delineated. In addition, it is not
      known if cultured lung-associated lymph node (LALN) cells can transfer EHP. PLN
      and LALN cells from donor animals were cultured with a soluble extract of
      Micropolyspora faeni (10 micrograms/ml), and blast cells were isolated by
      centrifugation over Percoll gradients. Cultured PLN cells were passed through
      nylon wool columns, and the adherent and nonadherent fractions were tested for
      their ability to transfer EHP. PLN blast cell populations were depleted of CD5+
      cells by treatment with monoclonal anti CD5 antibody (8BE6) and complement.
      Syngeneic recipients received media or LALN or PLN blast cells treated with
      antibody plus complement, media, or complement intravenously. Recipients were
      challenged intratracheally with M. faeni 48 h after the cell transfer, and they
      were killed 4 days later. The nonadherent PLN cell population was enriched for
      CD5+ (T) cells and depleted of surface immunoglobulin-positive (SIg+) cells.
      Treatment of the PLN blast cell population with 8BE6 and complement decreased
      CD5+ cells from 25 to 4% and increased SIg+ cells from 62 to 80%. All animals
      were maintained in HEPA-filtered air. Randomly selected microscopic fields of the
      lung (250/animal) were judged to be normal or abnormal without knowledge of
      treatment. There was a low level of pulmonary response to an intratracheal
      challenge of M. faeni in media recipients. There was a substantial increase (p
      less than 0.01) of the extent of pulmonary abnormalities in the animals receiving
      cultured PLN cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375011
TI  - Effect of somatostatin analogue and cholecystokinin receptor antagonist on bile
      induced acute canine pancreatitis.
AB  - To determine whether a synthetic somatostatin analogue, octreotide, and a
      cholecystokinin receptor antagonist, L-364,718, may be beneficial in acute
      pancreatitis, 33 dogs were assigned to four groups. Each dog underwent laparotomy
      with injection of autologous bile into the dorsal pancreatic duct. Thirty minutes
      after the induction of pancreatitis, Group 1 received a subcutaneous injection of
      octreotide (200 micrograms/kg), Group 2 received an equal volume of the
      octreotide carrier, Group 3 received an hourly intravenous bolus of L-364,718 (60
      micrograms/kg), and Group 4 received an equal volume of the L-364,718 carrier.
      Hemodynamic profiles, arterial blood gases, plasma glucose, and serum amylase
      were obtained before laparotomy, at bile injection, and at hourly intervals. The
      pancreas was removed after 8 hours for gross evaluation, measurement of water
      content, and histologic examination. A significant decrease in cardiac index and
      a significant increase in serum amylase and pancreatic edema occurred in all four
      groups 8 hours after the induction of pancreatitis (P less than 0.05), but there
      was no statistical difference between any group. Likewise, there was no
      difference in gross or histologic changes in the pancreas of any group. The
      somatostatin analogue, octreotide, and the cholecystokinin receptor antagonist, L
      364,718, did not ameliorate the effects of severe, bile-induced pancreatitis in
      dogs.

PMID- 1375012
TI  - The Sweet syndrome during therapy with granulocyte colony-stimulating factor.

PMID- 1375013
TI  - Fabry disease: immunocytochemical characterization of neuronal involvement.
AB  - Fabry disease is an X-linked glycosphingolipid storage disease caused by
      deficiency of alpha-galactosidase. Storage of globotriaosylceramide, also known
      as ceramide trihexoside, is maximal in blood vessels but also occurs in neurons.
      We performed neuropathological histochemical studies on the brains and spinal
      cords of 2 patients with confirmed Fabry disease. Luxol fast blue-positive
      deposits were found in blood vessels throughout the central and peripheral
      nervous system and within selected neurons in spinal cord and ganglia, brainstem,
      amygdala, hypothalamus, and entorhinal cortex. Regions adjacent to involved
      neuronal groups, including nucleus basalis, striatum, globus pallidus, and
      thalamus, were spared. Electron microscopy showed lamellar cytoplasmic neuronal
      inclusion bodies. Using a monoclonal antibody reactive with ceramide trihexoside,
      we found more extensive neuronal deposition than evident by Luxol-fast blue
      staining and new areas of neuronal storage in the spinal cord and cerebral
      cortex. Blood vessels throughout the nervous system were strongly immunoreactive.
      The highly selective pattern of neuronal involvement we found suggests that
      glycosphingolipid exposure, uptake, or catabolism varies greatly with respect to
      neuronal morphology and distribution. The degree of toxicity to neurons and the
      clinical significance of this neuronal storage remains to be defined.

PMID- 1375015
TI  - Purification and characterization of O-acetylserine (thiol) lyase from spinach
      chloroplasts.
AB  - O-Acetylserine (thiol) lyase, the last enzyme in the cysteine biosynthetic
      pathway, was purified to homogeneity from spinach leaf chloroplasts. The enzyme
      has a molecular mass of 68,000 and consists of two identical subunits of Mr
      35,000. The absorption spectrum obtained at pH 7.5 exhibited a peak at 407 nm due
      to pyridoxal phosphate, and addition of O-acetylserine induced a considerable
      modification of the spectrum. The pyridoxal phosphate content was found to be 1.1
      per subunit of 35,000, and the chromophore was displaced from the enzyme by O
      acetylserine, leading to a progressive inactivation of the holoenzyme. Upon gel
      filtration chromatography on Superdex 200, part of the chloroplastic O
      acetylserine (thiol) lyase eluted in association with serine acetyltransferase at
      a position corresponding to a molecular mass of 310,000 (such a complex called
      cysteine synthase has been characterized in bacteria). The activity of O
      acetylserine (thiol) lyase was optimum between pH 7.5 and 8.5. The apparent Km
      for O-acetylserine was 1.3 mM and for sulfide was 0.25 mM. The calculated
      activation energy was 12.6 kcal/mol at 10 mM O-acetylserine. The overall amino
      acid composition of spinach chloroplast O-acetylserine (thiol) lyase was
      different than that determined for the same enzyme (cytosolic?) obtained from a
      crude extract of spinach leaves. A polyclonal antibody prepared against the
      chloroplastic O-acetylserine (thiol) lyase exhibited a very low cross-reactivity
      with a preparation of mitochondrial matrix and cytosolic proteins suggesting that
      the chloroplastic isoform was distinct from the mitochondrial and cytosolic
      counterparts.

PMID- 1375014
TI  - Preferential loss of striato-external pallidal projection neurons in
      presymptomatic Huntington's disease.
AB  - We have reported previously that striatal projection neurons are differentially
      affected in the course of Huntington's disease, and in a prior patient report we
      noted that differential loss of striatal projection neurons occurs also in
      patients with presymptomatic Huntington's disease. Striatal neurons projecting to
      the external segment of the globus pallidus or the substantia nigra show evident
      loss, whereas those projecting to the internal segment of the globus pallidus
      appear relatively spared at presymptomatic and early stages of symptomatic
      Huntington's disease. We now report similar findings in a second apparently
      presymptomatic Huntington's disease allele carrier.

PMID- 1375016
TI  - Urinary excretion of diethylphosphorus metabolites in persons poisoned by
      quinalphos or chlorpyrifos.
AB  - The urinary excretion rates of diethyl phosphate and diethyl phosphorothioate and
      changes in blood cholinesterase activities were studied in fifteen persons self
      poisoned either by the organophosphorus pesticide quinalphos (twelve persons) or
      by chlorpyrifos (three persons). The organophosphate poisoning was always
      indicated by a significant depression of serum and/or red blood cell
      cholinesterase activities. The return of serum cholinesterase activity in the
      range of referent values took more than 30 days and had a different course in
      different persons. The most rapid increase in red blood cell acetylcholinesterase
      activity was noted within 24 h after the first treatment with oximes Pralidoxime
      and/or HI-6. None of the spot urine samples, collected daily after admission of
      persons to hospital, contained measurable quantities of the parent pesticide.
      There was no correlation between the maximum concentration of total urinary
      diethylphosphorus metabolites normalized to creatinine and the initial inhibition
      of blood cholinesterase activities measured in samples collected on the day of
      admission to hospital. The excretion of metabolites followed the kinetics of a
      biphasic reaction. The half-time of urinary metabolites concentration decrease in
      the fast excretion phase in quinalphos poisoned persons was 5.5-14.2 h (eight
      persons) and 26.8-53.6 h (four persons) and in chlorpyrifos poisoned persons 3.5
      5.5 h. The half-time for the slow excretion phase ranged from 66.5 to 127.9 h in
      all persons and for both compounds. For a given person, the rates of excretion of
      diethyl phosphate and diethyl phosphorothioate were about the same. However, in
      quinalphos poisoned persons the proportions of single metabolites in total
      diethylphosphorus metabolites varied with the initial maximum concentration of
      total metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375017
TI  - Aquatic hazard assessment of the organophosphate insecticide fonofos.
AB  - This study determined the acute and chronic toxicity of the organophosphate
      insecticide fonofos to standard freshwater aquatic organisms under laboratory
      conditions. Fonofos was acutely toxic to bluegill (Lepomis macrochirus), Daphnia
      (D. magna), and midge (Chironomous riparius) at 5.3, 2.7, and 39 micrograms/L,
      respectively. Three fonofos formulations (technical, 94.8% A.I.; 20G, field
      granular 20% A.I.; and 4E, field liquid 4#/gal A.I.) exhibited similar acute
      toxicities to bluegill. Exposure to fonofos delayed reproduction and decreased
      the intrinsic rate of increase of Daphnia during 21-d chronic exposure at the
      lowest tested concentration (0.08 micrograms/L). The no observable effect
      concentration (NOEC) for Daphnia survival was 0.42 micrograms/L; 0% survival
      occurred at the lowest observable effect concentration (LOEC) of 1.45
      micrograms/L. The NOEC for midge emergence was 3.42 micrograms/L; only 34%
      emergence occurred at the LOEC of 8.24 micrograms/L. Chronic 30-d exposure of
      juvenile bluegills decreased growth and survival at 5.65 micrograms/L (LOEC), but
      no effects occurred at 2.33 micrograms/L (NOEC). The relative hazard of fonofos
      to aquatic life is similar to other carbamate and organophosphate corn
      insecticides.

PMID- 1375018
TI  - Sulphydryl reactivity of the HLA-B27 epitope: accessibility of the free cysteine
      studied by flow cytometry.
AB  - HLA-B27 has an unpaired cysteine on or near its serologically defined spondylitis
      associated epitope, and it has been argued that its sulphydryl side chain may be
      chemically reactive. In a previous study it was shown that chemical treatment of
      HLA-B27 cells with the sulphydryl binding agent p-chloromercuriphenylsulphonic
      acid (pCMPSA) specifically reduced binding of antibodies to HLA-B27 by up to 80%,
      as measured in a cellular enzyme linked immunosorbent assay (CELISA). The effect
      of sulphydryl blockade on intact B27 cells was investigated using flow cytometry.
      Compared with the CELISA, inhibition required higher concentrations of pCMPSA,
      and the degree of inhibition produced by a greater than or equal to 30 microM
      solution of pCMPSA as measured by flow cytometry (median 28.9%) was significantly
      lower than that measured by CELISA (median 73.6%; p = 1.6 x 10(-6)). Analysis of
      unfixed, cell surface HLA-B27 by flow cytometry suggests that on most B27
      molecules the unpaired sulphydryl site is not available. On the basis of this
      evidence for modification after translation, a new 'altered self' hypothesis is
      proposed for the part which HLA-B27 plays in inflammatory disease.

PMID- 1375019
TI  - Clinical and biologic response to clozapine in patients with schizophrenia.
      Crossover comparison with fluphenazine.
AB  - Twenty-one patients with schizophrenia who met criteria for neuroleptic treatment
      resistance or intolerance participated in a crossover, placebo-controlled, double
      blind comparison of long-term typical neuroleptic and clozapine treatment.
      Clozapine significantly reduced total as well as positive and negative symptoms
      in comparison with both fluphenazine and placebo. Of the 21 patients, eight (38%)
      showed clozapine superiority on the basis of prospective response criteria. High
      levels of extrapyramidal side effects during fluphenazine treatment and later
      onset of illness were clinical predictors of clozapine superiority. Clozapine and
      fluphenazine equally reduced plasma homovanillic acid levels in comparison with
      placebo, although fluphenazine but not clozapine increased plasma prolactin
      level. A striking biologic difference between clozapine and fluphenazine was
      clozapine's enhancement of indexes of noradrenergic activity. Superior clozapine
      response was predicted by low ratios of cerebrospinal fluid homovanillic acid to
      5-hydroxyindoleacetic acid, consistent with the notion that balance between
      dopaminergic and serotoninergic systems is important for clozapine's mechanism of
      action.

PMID- 1375020
TI  - The effects of sodium lauryl sulphate and its oxidative breakdown products on
      calcium phosphate precipitation and transformation.
AB  - Most commercial dentifrices contain sodium lauryl sulphate, which oxidizes upon
      storage. The effects of aged sodium lauryl sulphate and its oxidative breakdown
      products on the conversion of amorphous calcium phosphate to hydroxyapatite were
      studied in vitro by a pH drop method. Hydroxyapatite was identified from its X
      ray diffraction pattern. With storage time, the concentration of dodecanol
      [CH3(CH2)11OH], a breakdown product of sodium lauryl sulphate, increased. The
      storage dodecanol-containing sodium lauryl sulphate accelerated the conversion of
      amorphous calcium phosphate to hydroxyapatite. Dodecanol mixed with sodium lauryl
      sulphate accelerated the conversion when added both before and after initial
      formation of amorphous calcium phosphate. A stored commercial dentifrice also
      accelerated the conversion of amorphous calcium phosphate to hydroxyapatite. It
      was found that the concentration of dodecanol increased 2-fold over a 2-month
      period.

PMID- 1375021
TI  - Occurrence and distribution of different neurochemical markers in the human
      dental pulp.
AB  - The occurrence and distribution of neuronal markers in human premolar and molar
      pulps were studied immunohistochemically. In the apical and central parts of the
      pulp, evenly distributed, thick neurofilament-immunoreactive nerve bundles
      predominated, which in many instances accompanied blood vessels. In the coronal
      parts, especially in the pulp horns, such nerve bundles formed a subodontoblastic
      plexus, while thin neurofilament-immunoreactive fibres projected into the
      odontoblastic region. In the coronal parts of the pulp, thin, varicose,
      calcitonin gene-related peptide (CGRP)- and occasionally substance P
      immunoreactive fibres were observed in the pulp-dentine zone and also in the
      vicinity of blood vessels. Vasoactive intestinal polypeptide (VIP) fibres were
      distributed in several nerve bundles, while single VIP fibres were seen
      projecting into the odontoblastic region as well as in the vicinity of blood
      vessels. Peptide histidine isoleucine amide (PHI)-immunoreactive fibres showed a
      similar distribution as VIP, but were less common. Furthermore, neuropeptide Y
      immunoreactive fibres occurred occasionally around blood vessels in the inner
      parts of the pulp. Tyrosine hydroxylase-immunoreactive nerve fibres with a
      varicose appearance were observed in some nerve bundles, but were also frequently
      seen around and in blood vessels. In premolar pulps obtained from teeth with open
      apices a less dense neurofilament innervation was seen in the coronal pulp.
      However, no apparent difference in the occurrence and distribution of the other
      neuronal markers was found compared to mature teeth. The human dental pulp, thus,
      seems to have a rich occurrence of neuropeptides and tyrosine hydroxylase in
      thin, varicose fibres. However, the distribution of the fibres expressing
      immunoreactivity to these neuronal markers seems to be sparse in comparison to
      neurofilament-immunoreactive fibres.

PMID- 1375022
TI  - A biochemical analysis of parotid and submandibular salivary gland function with
      age after simultaneous stimulation with pilocarpine and isoproterenol in female
      NIA Fischer 344 rats.
AB  - This analysis of physiological, biochemical and molecular changes related to
      aging was made in 3-, 12- and 24-month-old rats. The salivary gland weight/body
      weight ratio and the structural membrane proteins did not change with age for
      either gland, but a significant age-related decline in DNA synthesis for both
      glands was detected, unrelated to the hormonal responsiveness at the level of the
      plasma membrane. There was a marked increase in the concentration of soluble
      proteins in adolescent parotid gland and, for the two older age groups, in
      submandibular gland. The saliva flow rate was different when expressed as volume
      per time, as volume per time and g glandular wet weight, and/or kg body weight.
      The concentration of secreted proteins was not affected by age in either gland.
      The total amount of proteins secreted over 30 min revealed no age-related
      perturbation for the parotid gland, but showed a significant age-related increase
      in submandibular saliva. Sodium dodecyl sulphate-polyacrylamide gel analysis
      revealed changes in the protein bands between 39 and 50 kDa in the Coomassie blue
      stained gels from 12-month-old animals. Amylase showed an initial increase (12
      months), followed by a marked decline in its activity in parotid saliva. The
      glandular supernatant had low residual cellular amylase activity after
      stimulation. Therefore, secretory impairment with age after pilocarpine
      isoproterenol stimulation was excluded. Analysis of total RNA showed a pronounced
      decrease of amylase mRNA in the parotid gland between 12 and 24 months of age. No
      amylase mRNA was expressed in any of the submandibular samples. For epidermal
      growth factor, total saliva showed a decrease with age. It seemed that the
      submandibular gland followed the same picture with age as the parotid gland, with
      a specific decline in the biosynthesis of single secretory proteins.

PMID- 1375023
TI  - The effects of growth factors on DNA synthesis, proteoglycan synthesis and
      alkaline phosphatase activity in bovine dental pulp cells.
AB  - Platelet-derived growth factor (PDGF), insulin-like growth factor-I and -II (IGF
      I and -II), acidic fibroblast growth factor (aFGF), basic fibroblast growth
      factor (bFGF) and epidermal growth factor (EGF) stimulated [125I]-deoxyuridine
      incorporation about 13, 6.2-, 4.6-, 3.8-, 3.1- and 1.2-fold, respectively, above
      control values at a concentration of 50 ng/ml. Transforming growth factor-beta
      (TGF-beta) decreased incorporation about 30% at the same dose. aFGF, IGF-I, IGF
      II, bFGF and TGF-beta increased [35S]-sulphate incorporation 231, 71, 64, 42 and
      39%, respectively, in proliferating cells, while EGF, IGF-I, TGF-beta and PDGF
      decreased incorporation about 30%, and aFGF increased incorporation 80% in
      stationary-stage culture. TGF-beta, PDGF, aFGF and bFGF caused 65-40% inhibition
      of alkaline phosphatase activity in proliferating and stationary cultures. These
      findings suggest that the proliferation of pulp cells may be stimulated mainly by
      PDGF and IGF-I, and the production of extracellular matrix proteoglycan may be
      enhanced by aFGF, IGF-I and IGF-II. Furthermore, TGF-beta, PDGF, aFGF and bFGF
      may regulate the differentiation of pulp cells into odontoblasts.

PMID- 1375024
TI  - A comparison of bladder neck incision and transurethral prostatic resection.
AB  - Between 1978 and 1988, 108 patients underwent bladder neck incision (BNI) for
      bladder outflow obstruction. These patients were compared to a similar group who
      underwent transurethral resection of the prostate (TURP), during the same time
      period. Only patients with minimal prostatic enlargement (less than 10 g) with
      prominent bladder necks and small lateral lobes were included in the study. In
      addition, all patients in the resection group had a resection weight of less than
      10 g on the histopathology report. Patients were followed up by means of a posted
      questionnaire to which 59 patients in the BNI group and 86 in the TURP group
      responded. Pre-operative and peri-operative data were also collected from these
      respondents by a retrospective case record review. This found both operations to
      be safe with low morbidity and mortality. BNI was better than TURP in terms of
      shorter operation length (P less than 0.017) and shorter duration of
      catheterization (P less than 0.004). No other peri-operative differences were
      found. Follow-up results from the questionnaire showed no significant differences
      in symptoms between the two groups. Similarly, there was no difference in the
      number of re-operations performed over the 10 year period studied. Patient
      assessment of their operation was initially favourable in both groups (greater
      than 80% patient approval) however, both treatment groups experienced a gradual
      drop in patient approval over the 10 year period. There were no differences in
      the level of approval between the BNI and TURP groups.

PMID- 1375025
TI  - Influence of platelet activating factor antagonists on the protamine sulphate
      stimulated release of histamine from peritoneal mast cells of rats in vitro.
AB  - The phospholipase (PL)A2 inhibitor p-bromophenacyl bromide (p-BPB), the
      antagonists of the platelet activating factor (PAF) 3-(4-(2-chlorophenyl)-9
      methyl-6H-thieno(3,2-f)-(1,2,4)triazolo(4, 3-a)(1,4)diazepine-2-yl)-1-(4
      morpholinyl)-1-propanone (a thieno-triazolo-diazepine, WEB 2086) and terpene
      ginkgolide B and the antihistamine with PAF antagonistic qualities 4,9-dihydro-4
      (1-methyl-4-piperidinylidene)-10H-benzo[2,5]cyclo hep ta[1,2-b]thiophen-10-one
      (ketotifen) inhibit in the order p-BPB greater than terpene-ginkgolide B greater
      than ketotifen greater than WEB 2086 with decreasing activity the protamine
      sulphate activated histamine release from peritoneal rat mast cells (pRMC) in
      vitro. All compounds also inhibit the PAF induced aggregation of human platelets.
      The order of inhibition of the histamine release by these compounds does not
      agree with the order of their inhibitory activity on PAF induced aggregation of
      human platelets, indicating that the inhibition of the mast cell degranulation
      caused by PAF antagonists does not occur via PAF receptors. A generally membrane
      stabilizing quality of terpene-ginkgolide B and WEB 2086 may be ruled out as the
      cause of degranulation inhibition because none of the compounds suppresses the
      cytotoxic, triton X-100 induced release of histamine from pRMC. The mechanism of
      mast cell degranulation inhibition by PAF antagonists is unclear. An inhibition
      of PLA2 and/or inhibition of the Ca(2+)-activation are suggested.

PMID- 1375026
TI  - Glutamate-gated ion channels in the brain. Genetic mechanism for generating
      molecular and functional diversity.
AB  - L-glutamate is the major excitatory neurotransmitter in the vertebrate central
      nervous system. Most cells are responsive to glutamate which activates cation
      channels with different pharmacological, kinetic, and ion permeability
      properties. These channels play important roles in neurotransmission, memory
      acquisition as well as acute and chronic disorders of the brain. The present
      report summarizes recent knowledge on AMPA (a-amino-3-hydroxy-5-methyl-isoxazole
      4-propionic acid) receptors which mediate fast synaptic neurotransmission.

PMID- 1375027
TI  - Racemic epinephrine use in croup and disposition.
AB  - The purpose of this study was to determine the effectiveness of a protocol for
      the outpatient management of laryngotracheitis (croup) using racemic epinephrine
      and steroids. The authors retrospectively reviewed fifty consecutive charts of
      children with croup who were treated under this protocol in the Scottish Rite
      Children's Medical Center Emergency Department (Atlanta, GA) and discharged to
      home after 2 hours of observation. Forty-seven of the 50 children had stridor at
      rest and/or retracting at rest on presentation to the emergency department. Forty
      seven of the 50 patients did not require further medical care within 48 hours.
      One patient required another emergency visit and additional treatment with
      racemic epinephrine. Two patients were lost to follow-up. This study suggests
      that selected children presenting with croup and significant distress may be
      effectively treated with racemic epinephrine and steroids, observed for at least
      2 hours, and safely discharged home.

PMID- 1375028
TI  - Effects of N-methyl-N-nitrosourea on transcriptionally active and inactive
      nucleosomes: macromolecular damage and DNA repair.
AB  - We previously reported a separation, on an organomercurial column, of
      transcriptionally inactive nucleosomes (class 1) from those containing active
      gene sequences (classes 2 and 3). In this paper, we analyzed nucleosomal damage
      caused by exposure of HeLa S3 cells in suspension culture to the directly
      alkylating carcinogen N-methyl-N-nitrosourea (MNU). The extent and site of
      methylation induced by the compound in nucleosomal DNA and RNA were determined by
      cell incubation in the presence of [3H]MNU. The highest amount of damage was
      detected in DNA of class 3 nucleosomes, while RNA alkylation was comparable in
      all nucleosomal classes. Cellular capacity for repair of MNU-induced DNA strand
      breaks (estimated after a short pulse with [3H]thymidine) was found to be higher
      in active nucleosomal fractions (classes 2 and 3) than in the inactive fraction
      (class 1). Our data support the postulate that chromatin primary structure plays
      a role in modulating carcinogen damage to chromosomal macromolecules and in DNA
      strand breakage and repair mechanisms. Some of these initial steps are believed
      to be critical in the process of carcinogenesis.

PMID- 1375029
TI  - Testicular adenoma and seminal vesicle engorgement in polyomavirus large-T
      antigen transgenic mice.
AB  - Six lines of transgenic mice harboring the cDNA for polyomavirus large-T antigen
      (PVLT) linked to the mouse metallothionein-1 promoter were isolated. The
      transgene was expressed in testes in all lines isolated and in testes and seminal
      vesicles in two lines. Three lines developed enlarged testes and seminal
      vesicles. Development of the phenotype was divided into three stages separable by
      age and pathology. In stage 1, birth to 6 mo, PVLT was expressed in testes but no
      pathology was noted; in stage 2, 6-10 mo, PVLT was expressed solely in testes and
      not in seminal vesicles, yet the seminal vesicles were enlarged; and in stage 3,
      10 mo and older, both testes and seminal vesicles expressed PVLT and both were
      enlarged. Testes were up to sevenfold heavier and increased up to fourfold to
      fivefold in each dimension. Seminal vesicles were enlarged up to 20-fold as the
      result of an accumulation of seminal vesicle fluid. In addition to the four major
      proteins of seminal vesicle fluid, extra proteins, initially found in stage 2,
      were increased in stage 3 seminal vesicle fluid. The Leydig cell was the dominant
      cell type in affected testes; there were few or no normal Sertoli cells or
      seminiferous tubules remaining by stage 3. The Leydig cells were physiologically
      active, as indicated by a 8.5-fold higher testosterone level in sera from stage 3
      affected mice compared with sera from age-matched normal males. PVLT was present
      in the nuclei of the Leydig cells and was able to confer an immortal phenotype in
      vitro. Formation of the Leydig cell adenoma was dependent on PVLT expression, but
      since PVLT expression occurred much earlier than did pathology, additional
      secondary factors must determine the delay in phenotype development.

PMID- 1375030
TI  - Correlation of increased levels of Ha-ras T24 protein with extent of loss of gap
      junction function in rat liver epithelial cells.
AB  - Although it is known that cells transformed by ras and other oncogenes show
      reduced gap junction function, to date there has been no investigation of the
      quantitative relationship between intracellular levels of ras oncoprotein and
      loss of cell-cell communication. Using the rat liver epithelial cell line MTR6,
      which carries a zinc-inducible metallothionein ras T24 (MTrasT24) fusion gene, we
      showed a direct correlation between the accumulation of ras T24 protein and the
      loss of dye transfer as measured by interactive laser cytometry. After
      stimulation with zinc sulfate, changes in both parameters were rapid and
      measurable by 24 h. Similarly, there was a dose-response relationship between
      loss of gap junction function and increase in ras T24 protein. Northern analysis
      of two gap junction proteins (connexins 43 and 32) showed no differences between
      cells that expressed high levels of ras and control cells. These data demonstrate
      that the degree of loss of gap junction function is dependent on the amount of
      increase in ras T24 protein levels, but the mechanism by which these changes are
      effected remains unclear.

PMID- 1375031
TI  - Substance P-like immunoreactivity in the brain of the gymnotiform fish
      Apteronotus leptorhynchus: presence of sex differences.
AB  - The distribution of substance P-like immunoreactivity (SPli) was charted in the
      brain of the gymnotiform fish Apteronotus leptorhynchus, and correlated with the
      circuitry underlying intraspecific electrocommunication. Cell bodies were found
      predominantly in the lateral hypothalamus and in certain paraventricular organs:
      nucleus preopticus periventricularis, anterior subdivision; anterior
      hypothalamus; nucleus posterioris periventricularis; nucleus recessus lateralis,
      medial subdivision 2; nucleus recessus posterioris and nucleus recessus
      lateralis, lateral subdivision. Cell bodies were also found in the rostral
      olfactory nucleus, ventral telencephalon (ventral and central subdivisions), the
      habenula, the vagal sensory and motor nuclei and in the subtrigeminal nucleus.
      The distribution of SPli fibers was similar in some respects to that reported for
      other vertebrates. SPli was found in the rhombencephalon associated with vagal
      afferent fibers and in the funicular nucleus (possibly related to nociception).
      In the diencephalon and midbrain SPli fibers were found in the habenular
      interpeduncular tract, in the hypothalamus and pituitary. SPli fibers were also
      found in preoptic and forebrain areas. The most striking result was the sexually
      dimorphic SPli innervation of certain hypothalamic and septal nuclei, and of the
      prepacemaker nucleus (PPn), a diencephalic cell group which controls
      communication ('chirping') in gymnotiforms. The PPn and septal/hypothalamic
      nuclei were densely innervated by SPli in males but devoid of SPli in females.

PMID- 1375032
TI  - Calcitonin gene-related peptide in the human trigeminal sensory system at
      developmental and adult life stages: immunohistochemistry, neuronal morphometry
      and coexistence with substance P.
AB  - The distribution of calcitonin gene-related peptide (CGRP) has been examined by
      the indirect immunofluorescence technique in the Gasserian ganglion and spinal
      nucleus of the human trigeminal nerve. In the ganglion CGRP is present in almost
      50% of primary sensory neurons, in varicose and non-varicose nerve fibres and in
      pericellular basket-like plexuses around non-immunoreactive ganglionic perikarya.
      Morphometric analysis reveals that the CGRP-positive neuronal population is
      heterogeneous in cell size. Observation of specimens from subjects at fetal,
      perinatal and adult life stages reveals that the percentage of CGRP
      immunoreactive cells reaches a maximum at perinatal stages and then remains
      constant, declining only in old age. Pericellular basket-like nerve fibres are
      detectable only in fetal and pre-term and full-term newborn tissue. Coexistence
      between CGRP and substance P (SP) occurs, SP being present in about one quarter
      of the CGRP-immunoreactive neurons and CGRP being localized in a little more than
      half of the SP-immunoreactive neurons. However, perikarya, nerve fibres and
      pericellular fibres containing only one or other peptide are also present.
      Bundles of immunoreactive fibres and dot-like nerve terminals occur in the spinal
      tract and superficial and deep regions of the spinal trigeminal nucleus. A
      particularly dense plexus is present in the peripheral nuclear layers. Double
      immunostaining shows a similar regional distribution for SP. However, in inner
      substantia gelatinosa the density of CGRP-immunoreactive fibres is much higher
      than that of SP-immunoreactive ones. The results obtained add information to our
      knowledge of the organization of neurochemically identified neurons in the human
      trigeminal sensory system.

PMID- 1375033
TI  - Multidrug resistance: prospects for clinical management.
AB  - Clinical success in the treatment of tumors with chemotherapy has significantly
      improved over the past several years. However, treatment failures due to drug
      resistance of cancer cells has remained a major problem. The classical form of
      multiple drug resistance is perhaps also the most common type of drug resistance,
      and represents the overexpression of a transmembrane glycoprotein pump (P-170)
      that mediates the efflux of a spectrum of structurally and functionally unrelated
      drugs. Here, we discuss recent evidence that support the concept that the total
      phenomenon of multiple drug resistance (MDR) involves several other mechanisms in
      addition to that underlying "classical" MDR. These include the action of other
      energy-dependent membrane efflux pumps, elevated levels of GSH for drug
      conjugation and detoxification to facilitate export, enhanced DNA repair
      facility, gene amplification and oncogene activation. The combination of
      mechanisms used by any particular cell line is variable and suggests that many of
      these mechanisms are independent. Successful reversal of drug resistance appears
      to require the identification of relevant operative resistance mechanisms. An
      example is the competitive inhibition of P-170 with verapamil, quinine and
      tamoxifen. A broadly successful strategy for killing drug-resistant cancer cells,
      however, could be based on either selective energy depletion of cancer cells or
      the permeabilization of tumor cells with an effective bypass of efflux pumps,
      since many mechanisms of drug resistance entail the energy-dependent export of
      toxins. The latter approach may be achieved via membrane lipid modifications or
      the introduction of membrane pores by biological or physical (electroporation)
      means.

PMID- 1375034
TI  - Altered expression of ABO (H) carbohydrate antigens is seen in pleomorphic
      adenomas.
AB  - Cell surface carbohydrate antigens show changes in relation to differentiation,
      maturation and malignant transformation. The expression of type 2 chain ABH
      carbohydrate structures of the ABO histo-blood group system was investigated in
      28 pleomorphic adenomas (PA) and normal parotid glands in order to study possible
      changes in the glycosylation pattern. The distribution of carbohydrate structures
      was investigated by immunohistological stainings of formalin-fixed paraffin
      embedded material using monoclonal antibodies (MAbs) with well-defined
      specificity. A strong interindividual variation was found in the normal tissue as
      well as in the tumors. In normal tissue, acinus and duct cells all expressed
      elongated carbohydrate structures. The yoepithelial cells did not stain with any
      of the MAbs investigated. In the PAs, staining was seen in the ductular
      structures and myoepithelial cells. In contrast to normal tissue, the tumors
      expressed the short precursor molecule sialylated N-acetyllactosamine.
      Furthermore, the PAs showed loss of H and A antigens, and a reduced expression of
      Le(y) compared to normal tissue. The ductular structures as well as the modified
      myoepithelial cells expressed binary N-acetyllactosamine, which in the normal
      tissue could only be found in the striated and excretory ducts. Thus our study
      has shown that aberrant glycosylation is not only a feature of malignant
      neoplasms but also occurs in pleomorphic adenomas.

PMID- 1375035
TI  - Cystic fibrosis transmembrane conductance regulator: a chloride channel with
      novel regulation.

PMID- 1375036
TI  - Neural cell adhesion molecules modulate tyrosine phosphorylation of tubulin in
      nerve growth cone membranes.
AB  - Triggering neural cell adhesion molecules of the immunoglobulin superfamily with
      specific ligands or antibodies inhibited the phosphorylation of tryosyl residues
      in a subpopulation of alpha- and beta-tubulin associated with membranes from a
      subcellular fraction of nerve growth cones from fetal rat brain. Preincubation of
      these membranes with purified extracellular fragments of L1, N-CAM, or myelin
      associated glycoprotein, or with antibodies directed against the extracellular
      domains of L1 or N-CAM, inhibited pp60c-src-dependent phosphorylation of tubulin
      in an endogenous membrane kinase reaction. Other proteins that affect neurite
      outgrowth (fibronectin, laminin, antibodies against N-cadherin) had no effect.
      The results suggest that cell adhesion molecules transduce cell surface events to
      intracellular signals by modulating the activity of protein tyrosine kinases or
      phosphatases in axonal membranes to influence cytoskeletal dynamics at the growth
      cone.

PMID- 1375037
TI  - The chicken neural extracellular matrix molecule restrictin: similarity with EGF
      , fibronectin type III-, and fibrinogen-like motifs.
AB  - Restrictin is a chick neural extracellular matrix protein implicated in neural
      cell attachment and found to be associated with the cell surface recognition
      protein F11. Here we show by cDNA cloning that restrictin is a large multidomain
      protein composed of 4 structural motifs. At the N-terminus restrictin contains a
      cysteine-rich segment of about 140 aa that might link restrictin monomers into
      oligomers. This region is followed by 4.5 epidermal growth factor-like repeats
      and then by 9 consecutive motifs that are similar to fibronectin type III motifs.
      At the C-terminus restriction is related to the beta and gamma chains of
      fibrinogen, including similarity to a calcium-binding segment. Restrictin shows
      substantial sequence similarity with tenascin (cytotactin) throughout the
      polypeptide, and like tenascin, it forms oligomeric structures, as revealed by
      electron microscopy of immunoaffinity-purified restriction. The cell attachment
      site of restrictin is mapped to the C-terminal region by antibody perturbation
      experiments.

PMID- 1375038
TI  - The trkB tyrosine protein kinase is a receptor for neurotrophin-4.
AB  - Neurotrophin-4 is a novel member of the nerve growth factor family of
      neurotrophins recently isolated from Xenopus and viper DNA. We now report that
      the Xenopus NT-4 protein (XNT-4) can mediate some of its biological properties
      through gp145trkB, a murine tyrosine protein kinase previously identified as a
      primary receptor for the related brain-derived neurotrophic factor (BDNF). XNT-4
      displaces 125I-labeled BDNF from binding to cells expressing gp145trkB receptors,
      induces their rapid phosphorylation on tyrosine residues, and causes the
      morphologic transformation of NIH 3T3 cells when coexpressed with gp145trkB.
      Moreover, XNT-4 induces the differentiation of PC12 cells into sympathetic-like
      neurons only if they ectopically express gp145trkB receptors. None of these
      biochemical or biological effects could be observed when XNT-4 was added to cells
      expressing the related receptors. Replacement of one of the extracellular
      cysteines (Cys-345) of gp145trkB by a serine residue prevents its activation by
      XNT-4 but not by BDNF. Therefore, XNT-4 and BDNF may interact with at least
      partially distinct domains within the gp145trkB receptor.

PMID- 1375039
TI  - The neurotrophins BDNF, NT-3, and NGF display distinct patterns of retrograde
      axonal transport in peripheral and central neurons.
AB  - The pattern of retrograde axonal transport of the target-derived neurotrophic
      molecule, nerve growth factor (NGF), correlates with its trophic actions in adult
      neurons. We have determined that the NGF-related neurotrophins, brain-derived
      neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are also retrogradely
      transported by distinct populations of peripheral and central nervous system
      neurons in the adult. All three 125I-labeled neurotrophins are retrogradely
      transported to sites previously shown to contain neurotrophin-responsive neurons
      as assessed in vitro, such as dorsal root ganglion and basal forebrain neurons.
      The patterns of transport also indicate the existence of neuronal populations
      that selectively transport NT-3 and/or BDNF, but not NGF, such as spinal cord
      motor neurons, neurons in the entorhinal cortex, thalamus, and neurons within the
      hippocampus itself. Our observations suggest that neurotrophins are transported
      by overlapping as well as distinct populations of neurons when injected into a
      given target field. Retrograde transport may thus be predictive of neuronal types
      selectively responsive to either BDNF or NT-3 in the adult, as first demonstrated
      for NGF.

PMID- 1375040
TI  - Localization of acidic fibroblast growth factor within the mouse brain using
      biochemical and immunocytochemical techniques.
AB  - The localization of acidic fibroblast growth factor (aFGF) in the male mouse
      brain was studied with biochemical and immunocytochemical techniques. Using two
      peptide-based aFGF antisera directed against independent epitopes, Western gel
      analysis of dissected brain demonstrated significant levels of aFGF
      immunoreactivity in the pons-medulla, hypothalamus and cerebellum. The cortex
      contained much less immunoreactivity. Consistent with the biochemical data,
      immunocytochemical analysis with the same two antisera demonstrated that aFGF
      immunoreactivity is localized in neuronal cell bodies in these regions. Numerous
      immunoreactive neurons were observed in the reticular formation of the pons and
      medulla, as well as in several other brainstem nuclei and areas. Immunoreactive
      neurons were also present in the lateral and medial hypothalamus, and some
      thalamic, subthalamic and epithalamic nuclei. In the basal ganglia,
      immunoreactive neurons were present in the amygdala and septum. Few intensely
      stained immunoreactive neurons were observed in the striatum, pallidum and
      neocortex. Limbic cortices contained more numerous immunoreactive neurons than
      neocortex. These results support the concept that aFGF is present in the brain,
      where it is heterogeneously distributed in neuronal cell bodies in regions
      involved in sensory, extrapyramidal motor, limbic and autonomic functions. The
      results are consistent with various neurotrophic, mitogenic, and neuromodulatory
      functions associated with aFGF in the mammalian central nervous system.

PMID- 1375041
TI  - Distribution of acidic and basic fibroblast growth factors (FGF) in the foetal
      rat eye: implications for lens development.
AB  - Previously we reported that, in vitro, lens cells proliferate, migrate or
      differentiate in response to low, medium and high concentrations of FGF
      respectively. To examine further the role of FGF in lens development we used
      immunohistochemistry to study the distribution of aFGF and bFGF in the eye of the
      20 day rat foetus. Strong aFGF-like reactivity was localised in a band of cells
      near the lens equator which included the germinative zone where most cell
      proliferation occurs and the transitional zone where epithelial cells
      differentiate into fibres. The closely apposed inner epithelial layer of the
      ciliary and iridial retina also reacted strongly. Reactivity for aFGF was also
      found in the epidermis and in the corneal and conjunctival epithelia. In the
      neural retina, reactivity was found in the nerve fibre layer and in isolated
      cells of the inner plexiform layer. bFGF-like reactivity was found in the retinal
      ganglion cell layer, extra-ocular muscles and associated with endothelial cells
      of the hyaloid, lenticular and choroid vasculatures. Pre-digestion of sections
      with hyaluronidase caused loss of cell-associated reactivity but revealed strong
      bFGF-like reactivity in ocular basement membranes, in particular, the lens
      capsule. The sensitivity of this capsular bFGF localisation to heparinase
      indicates that bFGF in the extracellular matrix is complexed with heparan
      sulphate proteoglycans. The results of this study are consistent with the
      hypothesis that FGF plays an important role in lens development via both
      autocrine and paracrine mechanisms.

PMID- 1375042
TI  - Effect of recombinant human granulocyte colony-stimulating factor on survival in
      lethally irradiated mice.
AB  - Repeated injections of recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) to lethally irradiated mice increased the rate of animal survival. Dose
      modification factor was 1.20 when 4.5 micrograms/mouse of rhG-CSF was given daily
      for 14 days after whole body irradiation. Haematological examinations revealed
      that rhG-CSF increased the number of blood-circulating leukocytes, neutrophils,
      monocytes and erythrocytes, but not that of lymphocytes and thrombocytes. Spleen
      weight and number of endogenous spleen colonies were also increased by rhG-CSF
      treatment compared with the values for mice irradiated only.

PMID- 1375044
TI  - Chromium: trace elements in endocrinology. Proceedings of the 3rd International
      Congress on Trace Elements in Medicine and Biology. Les Deux Alpes, France,
      January 15-17, 1991.

PMID- 1375043
TI  - Avascular necrosis of the femoral head after treatment of Hodgkin's disease.

PMID- 1375045
TI  - Chromium content in human milk, cow's milk, and infant formulas.
AB  - Chromium was measured by Electrothermal Atomic Absorption Spectrometry in human
      milk, cow's milk, and infant formulas. The mean levels found were 1.56, 0.83, and
      4.84 (13%) micrograms/L, respectively. According to our data, the daily intake
      for the Spanish neonates is lower than the Recommended Dietary Allowances (RDAs)
      (10-40 micrograms/d) for this element.

PMID- 1375047
TI  - Dietary chromium intake. Freely chosen diets, institutional diet, and individual
      foods.
AB  - Chromium content of 22 daily diets, designed by nutritionists to be well
      balanced, ranged from 8.4 to 23.7 micrograms/1000 cal with a mean +/- SEM
      chromium content of 13.4 +/- 1.1 micrograms/1000 cal. Most diary products are low
      in chromium and provide less than 0.6 micrograms/serving. Meats, poultry, and
      fish are also low in chromium, providing 2 micrograms of chromium or less per
      serving. Chromium contents of grain products, fruits, and vegetables vary widely,
      with some foods providing greater than 20 micrograms/serving. In summary,
      chromium content of individual foods varies, and is dependent upon chromium
      introduced in the growing, transport, processing, and fortification of the food.
      Even well-balanced diets may contain suboptimal levels of dietary chromium.

PMID- 1375046
TI  - Glucose tolerance factor potentiation of insulin action in adipocytes from rats
      raised on a torula yeast diet cannot be attributed to a deficiency of chromium or
      glucose tolerance factor activity in the diet.
AB  - The nature of the dietary component responsible for adipocytes having the ability
      to respond to Glucose Tolerance Factor (GTF) was investigated. Rats were raised
      on either a control diet or one of three diets differing only in the protein
      source (torula yeast, brewer's yeast, or casein). Only in adipocytes from rats
      fed the torula yeast diet did a GTF fraction prepared from brewer's yeast
      potentiate the action of suboptimal concentrations of insulin in the
      incorporation of label from D-[1-14C]-glucose and D-[U-14C]-glucose into CO2 and
      fatty acids. It was concluded that this potentiation was not the result of a
      deficiency of GTF activity in torula yeast, because a GTF fraction prepared from
      torula yeast had similar insulin potentiating activity. Differences in response
      among diets were not owing to differences in levels of amino acids or owing to
      concentrations of 22 (Al, As, B, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mo, Na, Ni, P, Pb
      S, Se, Si, Sn, Sr, Zn) of the 23 trace elements investigated. The level of Mn was
      low in all diets, but particularly low in the torula yeast diet. Mn deficiencies
      have previously been implicated in perturbations of glucose metabolism, so that
      it is possible that this deficiency may be responsible for the effects attributed
      to the torula yeast diet.

PMID- 1375048
TI  - Chromium in the elderly.
AB  - Several studies indicate that glucose tolerance improves and lipid levels decline
      in the elderly after supplementation with Cr-rich brewer's yeast or inorganic Cr.
      Other studies report equivocal results or no changes. Interpretation of these
      investigations is hampered by 1. Lack of a marker to identify Cr-deficient people
      2. Artifactually high levels of dietary and body Cr, owing to inadequate analytic
      techniques and 3. The interplay of chronic health problems, medications,
      institutionalization, and dietary practices. Investigators have studied the
      effects of aging on Cr in the body. In the rat, tissue retention of 51Cr
      decreases, and organ distribution changes with age. In humans, plasma Cr levels
      of healthy elderly subjects are not different from those of young adults. There
      is no evidence of malabsorption in aged humans or animals. Nevertheless, higher
      urinary Cr losses are reported in elderly people. These data suggest that Cr
      retention may decrease with aging and that aging may alter Cr metabolism. Diets
      of many healthy elderly people contain less than 30 micrograms Cr. Two elderly
      men living under controlled conditions maintained Cr balance with 37
      micrograms/d. However, these levels may be insufficient during the stresses and
      illnesses associated with aging.

PMID- 1375049
TI  - A study of chromium in human cataractous lenses and whole blood of diabetics,
      senile, and normal population.
AB  - Chromium (Cr) is of known biological importance, necessary for the maintenance of
      normal glucose metabolism. There is a lower level of blood Cr concentrations in
      cases of diabetes. Diabetes carries a risk of cataract development, so the
      potential effects of Cr on the eye may need to be studied in more depth. The
      presence of this trace element in both normal and cataractous human lenses has to
      our knowledge not been investigated so far. The concentration of total Cr in 61
      human lenses and 38 blood samples was determined by electrothermal atomic
      absorption spectrometry with Zeeman effect (EAASZ). Analysis of the levels of Cr
      in human lenses shows a significant difference between normal and diabetic
      populations, and an absence of difference between senile and diabetic
      populations.

PMID- 1375050
TI  - Total chromium in the human lens. Determination with Zeeman electrothermal atomic
      absorption spectrometry following mineralization in a mini-autoclave.
AB  - A simple, quick procedure has been developed for preparation of human lenses for
      total chromium (Cr) analysis by electrothermal atomic absorption spectrometry
      (EAAS). This procedure involves wet ashing in a mini-autoclave with HNO3 and
      H2SO4. Recovery was 101.6%. This procedure is simple to carry out, does not
      generate corrosive fumes, and minimizes contaminations. Measurements obtained by
      this method give values similar to those found previously by more cumbersome
      methods. It can be conveniently used to prepare biological samples for ultratrace
      analysis. The mean Cr concentration in human lenses varied between 0.345 +/-
      0.147 micrograms/g dry wt in the normal population and 0.205 +/- 0.160
      micrograms/g dry wt in cataractous lenses.

PMID- 1375052
TI  - Hair, serum, and urine chromium concentrations in former employees of the leather
      tanning industry.
AB  - In this study, we measured concentrations of Cr in hair, serum, and urine of men
      who were previously employed in the leather tanning industry. Concentrations of
      Cr in hair and serum were significantly lower than corresponding values obtained
      during their employment and were comparable to levels obtained for controls in a
      previous study. These results suggest that Cr III accumulated from employment in
      the leather tanning industry does not result in long-term elevation of Cr
      concentrations in the body.

PMID- 1375051
TI  - Toxic effects of chromium and its compounds.
AB  - Chromium was discovered in 1797 by Vauquelin. Numerous industrial applications
      raised chromium to a very important economic element. At the same time, with the
      development of its uses, the adverse effects of chromium compounds in human
      health were being defined. Trivalent chromium is an essential trace element in
      humans and in animals. Chromium as pure metal has no adverse effect. Little toxic
      effect is attributed to trivalent chromium when present in very large quantities.
      Both acute and chronic toxicity of chromium are mainly caused by hexavalent
      compounds. The most important toxic effects, after contact, inhalation, or
      ingestion of hexavalent chromium compounds are the following: dermatitis,
      allergic and eczematous skin reactions, skin and mucous membrane ulcerations,
      perforation of the nasal septum, allergic asthmatic reactions, bronchial
      carcinomas, gastro-enteritis, hepatocellular deficiency, and renal oligo anuric
      deficiency. Prevention of occupational risks, biological monitoring of workers,
      and treatment of poisoning are also reported.

PMID- 1375053
TI  - Hydroxyl radical formation and lipid peroxidation enhancement by chromium. In
      vitro study.
AB  - Chromium VI compounds have been shown to be carcinogenic in occupationally
      exposed humans, and to be genotoxic, mutagenic, and carcinogenic in a variety of
      experimental systems. In contrast, most chromium III compounds are relatively
      nontoxic, noncarcinogenic, and nonmutagenic. Reduction of Cr6+ leads to reactive
      intermediates, such as Cr5+, Cr4+, or other radical species. The molecular
      mechanism for the intracellular Cr6+ reduction has been the focus of recent
      studies, but the details are still not understood. Our study was initiated to
      compare the effect of Cr(6+)-hydroxyl radical formation and Cr(6+)-induced lipid
      peroxidation vs those of Cr3+. Electron spin resonance measurements provide
      evidence for the formation of long-lived Cr5+ intermediates in the reduction of
      Cr6+ by glutathione reductase in the presence of NADPH and for the hydroxyl
      radical formation during the glutathione reductase catalyzed reduction of Cr6+.
      Hydrogen peroxide suppresses Cr5+ and enhances the formation of hydroxyl radical.
      Thus, Cr5+ intermediates catalyze generation of hydroxyl radicals from hydrogen
      peroxide through a Fenton-like reaction. Comparative effects of Cr6+ and Cr3+ on
      the development of lipid peroxidation were studied by using rat heart homogenate.
      Heart homogenate was incubated with different concentrations of Cr6+ compounds at
      22 degrees C for 60 min. Lipid peroxidation was determined as thiobarbituric acid
      reacting materiels (TBA-RM). The results confirm that Cr6+ induces lipid
      peroxidation in the rat heart homogenate. These observations might suggest a
      possible causative role of lipid peroxidation in Cr6+ toxicity. This enhancement
      of lipid peroxidation is modified by the addition of some metal chelators and
      antioxidants. Thus, strategies for combating Cr6+ toxicity should take into
      account the role of the hydroxy radicals, and hence, steps for blocking its chain
      propagation and preventing the formation of lipid peroxides.

PMID- 1375054
TI  - Clinical implications of trace elements in endocrinology.
AB  - The implications of essential trace elements in endocrinological processes,
      mainly thyroid function, growth, gonadal function, adrenal hormones, prolactin,
      glucose homeostasis, calcium-phosphorus metabolism, and thymulin activity, are
      reviewed. Most concerned elements in this field include iodine, zinc, selenium,
      copper, chromium, manganese and vanadium. The minerals are powerful modulators of
      several physiological functions that can be considerably perturbed in deficiency
      states. The resulting biochemical and clinical modifications can be prevented
      and/or corrected by adequate supplementation. Sometimes, however, they act like
      pharmacological agents when their beneficial effects are not the result of a
      correction of a nutritional deficiency state. Their potentialities as therapeutic
      agents are perfectly described in many cases, but some indications deserve
      further investigations.

PMID- 1375056
TI  - Chromium, glucose tolerance, and diabetes.
AB  - Chromium functions in maintaining normal glucose tolerance primarily by
      regulating insulin action. In the presence of optimal amounts of biologically
      active chromium, much lower amounts of insulin are required. Glucose intolerance,
      related to insufficient dietary chromium, appears to be widespread. Improved
      chromium nutrition leads to improved sugar metabolism in hypoglycemics,
      hyperglycemics, and diabetics.

PMID- 1375055
TI  - Endocrine regulation of trace element homeostasis in the rat.

PMID- 1375057
TI  - Absorption and metabolism of oral zinc gluconate in humans in fasting state,
      during, and after a meal.
AB  - The absorption and metabolism of zinc in a commercial form for oral use
      (Rubozinc, 15 mg zinc as gluconate) were investigated in 10 subjects by a kinetic
      study of the serum zinc profile after administration of 45 mg zinc under three
      conditions: after an overnight fast, during a standardized breakfast, and 2 h
      after this meal. The pharmacokinetic parameters were calculated by a method
      suitable to the characterization of rebound effects (recycling of the element in
      the gastrointestinal tract). In fasting state, the parameters were comparable to
      those previously collected in the same subjects with oral 45 mg zinc as sulfate,
      except with very significantly higher Cmax and area under curve (AUC), showing a
      better bioavailability for zinc in the commercial form. The light meal perturbed
      the absorption process as evidenced by the significant increases in the lag time
      (+180%), the tmax (+57%), and the lag times for the first two cycles during the
      meal. However, the parameters returned to normal values 2 h after the meal. The
      Cmax only moderately decreased during the meal (31%) as did the AUC (-28%). An
      important delay in the absorption of zinc in the commercial form when taken
      during a meal was therefore demonstrated, but the effect on zinc bioavailability
      was only moderate.

PMID- 1375059
TI  - Iodine deficiency, other trace elements, and goitrogenic factors in the
      etiopathogeny of iodine deficiency disorders (IDD).
AB  - Severe goiter, cretinism, and the other iodine deficiency disorders (IDD) have
      their main cause in the lack of availability of iodine from the soil linked to a
      severe limitation of food exchanges. Apart from the degrees of severity of the
      iodine deficiency, the frequencies and symptomatologies of cretinism and the
      other IDD are influenced by other goitrogenic factors and trace elements.
      Thiocyanate overload originating from consumption of poorly detoxified cassava is
      such that this goitrogenic factor aggravates a relative or a severe iodine
      deficiency. Very recently, a severe selenium deficiency has also been associated
      with IDD in the human population, whereas in animals, it has been proven to play
      a role in thyroid function either through a thyroidal or extrathyroidal
      mechanism. The former involves oxidative damages mediated by free radicals,
      whereas the latter implies an inhibition of the deiodinase responsible for the
      utilization of T4 into T3. One concludes that: 1. Goiter has a multifactorial
      origin; 2. IDD are an important public health problem; and 3. IDD are a good
      model to study the effects of other trace elements whose actions in many human
      metabolisms have been somewhat underestimated.

PMID- 1375058
TI  - Cultured human skin fibroblasts absorb 65Zn. Optimization of the method and study
      of the mechanisms involved.
AB  - The radioactive isotope 65Zn was used to study the incorporation of zinc by
      cultured human skin fibroblasts. The development of the method for studying cell
      uptake of 65Zn in a minimal synthetic medium is presented. Kinetics carried out
      on control cultures up to 240 min indicated that zinc uptake occurred in three
      phases, the first being the most rapid. Temperature and pH affect zinc uptake, in
      favor of an active transport process. In addition, the rate of incorporation is
      considerably decreased during the first phases after adding potassium cyanide,
      during the last phases after adding sodium iodoacetate, and during all the phases
      if dithioerythritol is used. A hypothesis is therefore proposed according to
      which several types of mechanisms would be involved in zinc uptake by
      fibroblasts. At least a part of these mechanisms is energy-dependent.

PMID- 1375060
TI  - Contribution of milk to iodine intake in France.
AB  - A survey based on 838 samples of milk obtained from 537 dairies covering 70 of 95
      districts in France was organized to assess iodine content of milk and its
      contribution to total intake. Iodine levels were significantly higher in winter
      than in summer. Very low iodine contents (less than 25 micrograms I/kg) were
      found in the eastern part of the country (the Vosges, Jura, and the Alpes) and
      the Massif Central. During milk processing, much of the iodine is lost in the
      whey. The other significant sources of dietary iodine are fish and eggs. Iodized
      salt is sold only to households and not to industry. Even if about 20% of the
      iodine is lost over the first 3 mo, salt remains the main source for this trace
      element. It is concluded that, if iodized salt is not provided systematically for
      both domestic and agro-industrial use, then milk may be the most important source
      of iodine. This key role may explain seasonal and geographical variations in the
      frequencies of goiter in France.

PMID- 1375061
TI  - The isolation of glucose tolerance factors from brewer's yeast and their relation
      to chromium.
AB  - A new dietary factor, the glucose tolerance factor (GTF), was reported in 1957
      that improved impaired glucose tolerance in rats. Most studies on GTF have used
      brewer's yeast as the starting material, and it has been postulated that the
      active material is a low-mol wt organic complex containing Cr3+. It seemed thus
      important to isolate an active GTF from chromium-rich yeast (228 ppm Cr) obtained
      by incubation with chromium and to compare each fraction with corresponding ones
      from untreated yeast (0.48 ppm Cr). We developed an isolation and purification
      procedure by fractionation of yeast extract on an anion and cation exchange
      resin, and tested the GTF activity (glucose oxidation) on rat adipocytes. PIXE
      (proton-induced X-ray emission) was used to measure the chromium content of the
      individual fraction. Individual fractions with GTF activity did not differ
      between Cr-rich and Cr-deficient yeast, and there was no relationship between Cr
      content and GTF activity. This does not support the hypothesis that chromium is
      an obligatory constituent of the GTF, assuming that GTF is a unique substance.

PMID- 1375062
TI  - Selenium and rubidium changes in subjects with pathologically altered thyroid.
AB  - Concentrations of selenium and rubidium in groups of subjects with
      hyperthyroidism, carcinomas, or adenomas and in controls were determined by
      neutron activation analysis with coirradiated inorganic standards and IAEA
      reference material. Se was decreased in all pathological groups with the greatest
      modification in thyroids with carcinomas. Rb was elevated in all pathological
      groups with the greatest increase in carcinomas as well. According to the
      literature, Se has a protective effect on carcinogenity as well as on biochemical
      pathways in thyroid cells. There are no data in the literature on the effects of
      Rb in those cells. On the grounds of the present results, it seems possible to
      use the trapping of Rb for diagnostic purposes in cases of pathologically altered
      thyroids.

PMID- 1375063
TI  - Iodine intakes assessed by urinary iodine concentrations in healthy children aged
      ten months, two years, and four years.
AB  - Urinary iodine excretion was assessed in 642 healthy children aged 10 mo (n =
      243), 2 yr (n = 183), and 4 yr (n = 216) living in the Paris area and originating
      from continental France (60.3%), North Africa (13.8%), the West Indies (9.1%),
      West Africa (8.3%), Southeast Asia (4.8%), and southern Europe (3.8%). Mild
      impairment of neurological (reflexes, tone, audiometry) and intellectual
      development (Brunet-Lezine scale) was assessed in relation to iodine status.
      Iodine excretions (median values) were 18.4, 11.9, and 10.9 micrograms/100 mL at
      10 mo, 2 yr, and 4 yr, respectively, and risk of mild iodine deficiency (5-10
      micrograms/100 mL) was 18.1%, 34.8%, and 38.3% for the same age groups. No
      relationship was found between anthropometry, global development quotient, and
      iodine status. High hearing thresholds were more commonly associated with lower
      iodine excretion, suggesting mild hearing defects. In spite of iodine
      prophylaxis, the risk of mild to moderate iodine deficiency still exists in
      France and in a number of European countries. Evaluation of neurological sequels
      of borderline iodine status is a major public health problem in European
      communities.

PMID- 1375065
TI  - Effects of thyroparathyroidectomy on the distribution of bromine and iodine in
      rat tissues.
AB  - The concentrations of iodine (I) and bromine (Br) were measured by inductively
      coupled plasma mass spectrometry in the plasma, kidney, heart, liver, and brain
      of control and thyroparathyroidectomized (TPTX) rats without and with an
      additional intake of either NaI or NaBr, 0.5 and 5 mumol/kg/d, respectively, for
      21 d. In all groups, the highest concentrations of I and Br were found in the
      plasma. TPTX did not modify the concentrations of I in tissues, but slightly
      increased Br in plasma (+33%) and kidney (+24%). The additional intake of I with
      the drink induced an increase of I concentrations in the tissues tested (from 54
      to 191%), except brain, both in control and TPTX rats. This additional intake of
      I also increased Br levels in the plasma of control (+24%) and TPTX rats (+53%).
      The additional intake of Br with the drink induced an increase of Br levels in
      all the tested tissues, brain included (from 85 to 284%). The augmentation was
      higher in the tissues, particularly brain, of TPTX rats than of controls. The
      increase of Br in brain after an additional intake contrasts with the absence of
      increase of I given in the same conditions. This difference between I and Br
      probably results from the smaller radius of Br ion in comparison with I ion
      radius. In conclusion, TPTX did not modify the distribution of I in the tested
      tissues, but slightly increased the concentrations of Br in plasma and
      kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375064
TI  - Acute effects of various doses of iodide on thyroid iodine autoregulation. A
      study with 129I by means of analytical ion microscopy.
AB  - Analytical ion microscopy (AIM) was used to determine alterations in the thyroid
      follicular lumen 127I stores of Wistar rats injected with different doses of 129I
      (low specific activity radionuclide). Animals fed a normal iodine diet (10
      micrograms 127I/d) were divided into four groups: control group and three treated
      groups injected ip 24 h before sacrifice with 129I at doses of 10 micrograms
      (group 1), 30 micrograms (group 2), and 8500 micrograms (group 3). AIM was
      performed on thyroid semithin sections. The mean 129I concentration increased
      with the dose injected from group 1 (0.44 +/- 0.03 micrograms/mg, mean +/- SEM)
      to group 2 (2.05 +/- 0.14 micrograms/mg) and decreased in group 3 (0.57 +/- 0.08
      microgram/mg). When compared to control group (4.14 +/- 0.17 micrograms/mg), the
      mean 127I concentration was not changed in group 1 (4.52 +/- 0.07 micrograms/mg),
      but altered in the other groups: It was significantly increased (7.14 +/- 0.41
      micrograms/mg) in group 2 and slightly decreased (3.11 +/- 0.26 micrograms/mg) in
      group 3. These results underline the interest of AIM in the study of the effects
      of various doses of iodide on the thyroid autoregulation by iodide, a trace
      element actively trapped by this gland.

PMID- 1375066
TI  - Influence of thyroparathyroidectomy and thyroxine replacement on Cu and Zn
      cellular distribution and on the metallothionein level and induction in rats.
AB  - Thyroid hormones are involved in copper and zinc distribution in rat tissues. We
      examined the influence of thyroparathyroidectomy (TPTY) and of a replacement
      therapy by T4 on Cu and Zn organ distribution. MT levels were also measured both
      in basal conditions and after induction by cadmium. The results confirm that a
      lack of T4 modified Cu and Zn in serum and tissues. In serum, TPTY increased Cu
      (+15%) and ceruloplasmin (+18%), and decreased Zn (-18%). In tissues, Cu was
      altered in liver (+13%), kidney (-24%), heart (-16%) duodenum (-18%), and Zn in
      liver (+25%) and kidney (-10%). The soluble fractions (100,000 g supernatant)
      were mainly affected in liver and kidney, and the subcellular fractions in heart
      and duodenum. MT levels were modified in basal conditions only in liver (+57%)
      and kidney (-36%). T4 administration partially prevented the effect of TPTY on
      both elements and MT concentrations. Therefore, no evidence is provided for a
      direct role of T4 in the metabolism of MT in a way comparable to the effects of
      glucocorticoids. However, MT could mediate the consequences of TPTY on metal
      distribution in certain organs, such as liver and kidney.

PMID- 1375067
TI  - Selenium content of livers from sex-linked dwarf and normal broiler breeders.
      Influence of a thyrotropin-releasing hormone-induced growth hormone release.
AB  - Plasma concentrations of cGH, T3, and T4 were not different between dwarf and
      normal broiler breeders. Normal hens had a liver selenium content of 710 +/- 35
      ng/g, and dwarf hens 656 +/- nine ng/g (n = 8). Following injections into a wing
      vein of different doses (1.5, 3, 6, 12, and 24 micrograms/kg) of the hypothalamic
      hormone TRH, GH was increased after 15 min. This effect seemed to last longer in
      dwarf chickens. Plasma concentrations of T3 increased significantly 1 h after TRH
      in normal hens, but TRH was ineffective in raising T3 levels in dwarf animals.
      The selenium content of livers obtained following decapitation after 2 h was also
      increased in normal hens up to 902 +/- 42 ng/g using the highest dose of TRH (24
      micrograms/kg). This seemed not to be the case for dwarf animals. A much smaller
      number of hepatic cGH receptors was also found in dwarf hens, whereas the
      affinity of the hepatic GH receptor was not influenced by the genotype. It is
      concluded that the sex-linked dwarf hens are unable to increase their hepatic T4
      into T3 conversion following a TRH challenge probably because of a deficiency in
      hepatic GH receptors. The lower content of selenium in dwarfs and their inability
      to increase its uptake after TRH seem therefore to support the hypothesis that
      selenium has a direct role in the activity of the 5'-deiodinase complex.

PMID- 1375069
TI  - Chromium. History and nutritional importance.

PMID- 1375068
TI  - Peptidylglycine alpha-amidating monooxygenase activity and TRH and CRF
      biosynthesis. Role of copper.
AB  - Carboxy-terminal amidation of biologically active peptides, an important
      characteristic of more than half of these substances, occurs during the
      maturation process of peptide precursors. It is catalyzed by peptidylglycine
      alpha-amidating monooxygenase (PAM), an enzyme that is copper-dependent. We show
      here that alterations of copper stores in cultured cells from different origins
      (pancreas and hypothalamus) affect the immunoreactivity of thyrotropin-releasing
      hormone (TRH) and corticotropin-releasing factor (CRF) (two alpha-amidated
      peptides). This suggests that copper can affect neuropeptide biosynthesis and may
      play a role in the endocrine or central nervous system function.

PMID- 1375070
TI  - Zinc and insulin sensitivity.
AB  - Many studies have shown that zinc deficiency could decrease the response to
      insulin. In genetically diabetic animals, a low zinc status has been observed
      contrary to induced diabetic animals. The zinc status of human patients depends
      on the type of diabetes and the age. Zinc supplementation seems to have
      beneficial effects on glucose homeostasis. However, the mechanism of insulin
      resistance secondary to zinc depletion is yet unclear. More studies are therefore
      necessary to document better zinc metabolism in diabetes mellitus, and the
      antioxidant activity of zinc on the insulin receptor and the glucose transporter.

PMID- 1375071
TI  - Effects of diabetes type and treatment on zinc status in diabetes mellitus.
AB  - Zinc status was assessed in 53 diabetic patients: 18 insulin-dependent diabetic
      patients (IDDM), 22 noninsulin-dependent diabetic patients (NIDDM) treated with
      oral antidiabetic agents, and 13 insulin-treated, noninsulin-dependent diabetic
      patients (IRDM). Plasma zinc concentrations were in the usual range for healthy
      subjects in these three groups (15.3 +/- 0.9 mumol/L). Urinary zinc excretions
      were elevated in the IDDM group (18.3 +/- 4.1 mumol/24 h; p less than 0.01 vs
      normal) and in the NIDDM group (17.5 +/- 3.5 mumol/24 h; p less than 0.01 vs
      normal), but normal in the IRDM group (11.3 +/- 2.4 mumol/24 h). In 14 NIDDM
      patients treated with transient continuous sc insulin injections, urinary zinc
      decreased from 16.5 +/- 2.2 mumol/24 h before insulin treatment to 11.5 +/- 0.3
      mumol/24 h after insulin treatment without any modification in plasma zinc
      concentrations.

PMID- 1375072
TI  - Urinary zinc and its relationships with microalbuminuria in type I diabetics.
AB  - We investigated whether zincuria is associated with microalbuminuria in type I
      (insulin-dependent) diabetics (IDDM). In 169 IDDM, 215 overnight urine samples
      were collected for simultaneous assay of zinc and albumin. In 76 samples with
      excessive microalbuminuria (greater than 15 mg/L), zincuria was higher than in
      the 139 other samples (0.83 +/- 0.06 vs 0.58 +/- 0.03 mg/L p less than 0.001),
      though zincuria and microalbuminuria were not significantly correlated. An
      exercise provocation test was performed in 78 IDDM. Although microalbuminuria
      increased, zincuria did not change during the test. Another group of 83 IDDM
      underwent urinary zinc determination over a period of 1 h of recumbency. The 48
      patients who had a zincuria higher than the mean + 2 SD of control values had
      higher microalbuminuria at rest (48 +/- 16 micrograms/min vs 12 +/- 2 p less than
      0.01) and after exercise (111 +/- 33 vs 42 +/- 14 p less than 0.02) than the
      remaining 35 subjects. Both subgroups did not differ for zinc intake and
      zincemia. Thus, incipient nephropathy as detected by the measurement of
      microalbuminuria is associated with a highly significant increase in zinc
      excretion, which is not proportional to albumin leakage, nor is it amplified
      during exercise. Hyperzincuria is not explained by an increase in zinc intake and
      does not result in hypozincemia.

PMID- 1375073
TI  - Zinc and copper in the serum of diabetic patients.
AB  - The Zn/Cu ratio was examined in the serum of three groups of persons: healthy
      volunteers, diabetic patients on diabetic diet (NIDDM), and diabetic patients on
      diabetic diet and insulin (IDDM). Zinc, copper, the Zn/Cu serum ratio, and the
      blood glucose level were determined during fasting and 2 h after breakfast. Zn
      and Cu serum levels in NIDDM and IDDM patients were decreased. The Zn/Cu ratio
      was higher in both groups of diabetic patients. These changes in the Zn and Cu
      levels as well as in the Zn/Cu ratio were not related to chronic diabetic
      complications.

PMID- 1375074
TI  - Effect of acute zinc deficiency on insulin receptor binding in rat adipocytes.
AB  - Considerable data have been reported on the relationship between insulin
      resistance and zinc deficiency. In this study, insulin receptor binding was
      measured in isolated rat adipocytes. Two assays were carried out at 37 degrees C
      (binding and internalization) and 16 degrees C (binding) using 125I insulin 0.05
      20 nM. A decreased insulin receptor binding was observed in zinc-deficient rat
      adipocytes, but we could not make any distinction between the specific zinc
      depletion effects and the effects of the caloric restriction induced by zinc
      deficiency.

PMID- 1375076
TI  - Iron in granulocytes of nephrotic patients determined by Zeeman electrothermal
      atomic absorption spectrophotometry.
AB  - One of the major threats to patients undergoing maintenance hemodialysis is an
      increased susceptibility to infections caused by microorganisms, among which
      Yersinia or Listeria are frequently recovered. In patients receiving
      hemodialysis, iron overload owing to multiple transfusions plays an important
      role in the mechanisms underlying the susceptibility to bacterial infections,
      partially mediated by impaired neutrophil function. In order to assess the true
      role of iron at the cellular level, an AAS method was developed to measure the
      iron content of granulocytes. Iron levels in the granulocytes were determined in
      an apparently healthy population and in a population of iron-overloaded renal
      hemodialysis patients. Granulocytes were isolated by a method modified from
      Boyum. The analyses were performed using pyrocoated graphite tubes, and in one of
      the char steps, oxygen was used to facilitate ashing. The mean iron level found
      in the granulocytes from apparently normal persons was 4.07 fg/cell (n = 17) with
      a CV of 44%; the mean value for the dialysis patient group was 4.59 fg/cell (n =
      8) with a CV of 37%. There was no significant difference between the two groups,
      p = 0.70.

PMID- 1375075
TI  - Zinc bone loss in chronic renal failure and chronic metabolic acidosis.
AB  - The effects of chronic metabolic acidosis (CMA) on zinc (Zn) bone content and
      urinary excretion were examined in the presence of normal or reduced renal
      function together with some aspects of calcium (Ca) metabolism. Four groups of
      rats were compared. All were fed a 30% protein and 9 mg Zn/100 g diet. Two were
      uremic (U): The first developed acidosis (UA), which was suppressed in the other
      (UNA) by NaHCO3 supplement. Two other groups had normal renal function: One was
      normal (CNA), and the other had NH4Cl in the drinking water and acidosis (CA).
      Femur total Zn and Ca content was markedly reduced by CMA and was not affected by
      uremia. Zn urinary excretion was increased by CMA and unaltered by uremia. Ca
      urinary excretion was markedly reduced in uremic rats, but was enhanced in both
      acidotic conditions. Urinary Ca and Zn showed a strong correlation in uremic and
      in control rats. Plasma parathormone and 1,25(OH)2D3 were unchanged by CMA. These
      data are in agreement with a direct primary effect of CMA on bone in releasing
      buffers. CMA induces bone resorption and a parallel decrease of mineral bone
      components, such as Ca and Zn, with little or no role of PTH, 1,25(OH)2D3 and of
      uremia itself.

PMID- 1375077
TI  - Effects of acute prednisolone administration on plasma and liver copper in rats
      with adjuvant arthritis.
AB  - Several studies in animals and humans have shown that copper metabolism could be
      affected by inflammation or by corticosteroids. The relative importance of these
      two factors, often imbedded in clinical practice, was assessed by investigating
      the effects of acute prednisolone administration (30 mg/kg, ip) on healthy and
      adjuvant arthritis rats. Plasma copper levels were significantly higher in
      arthritic rats compared to healthy animals, whereas there was a slight, but
      nonsignificant increase in liver copper. Acute prednisolone administration in
      healthy rats resulted in a significant increase in plasma copper (10-15%) as
      early as 4 h after corticosteroid administration, which was maintained for 12 h.
      In arthritic rats, the response was much higher (25-40%), but somewhat delayed
      and shorter. Liver copper was not clearly modified by prednisolone treatment in
      both groups. This time-controlled study showed that acute prednisolone
      administration increased plasma copper in both healthy and arthritic rats, but in
      different ways, indicating that inflammation and corticosteroids may act
      synergistically.

PMID- 1375080
TI  - Comparative binding study of aluminum and chromium to human transferrin. Effect
      of iron.
AB  - The characteristics of aluminum and chromium binding to apo-transferrin (apo-tf)
      have been investigated and compared. Both metal ions were taken up by human
      transferrin forming complexes with the maximum absorbances at 405 nm for chromium
      transferrin (cr-tf) and 240 nm for aluminum-transferrin (Al-tf). In the presence
      of citric acid, chromium binding to transferrin is five times more than aluminum.
      The binding of aluminum or chromium to apo-transferrin was reduced by 18 and 22%
      in the presence of 200 ng/mL of iron. The binding of both metals to apo-tf
      appears to be pH dependent. In acidic pHs, less chromium and more aluminum
      binding occurred.

PMID- 1375079
TI  - Hormonal effects of zinc on growth in children.
AB  - Zinc deficiency impairs the metabolism of thyroid hormones, androgens, and above
      all growth hormones. In view of their important role in growth, it is not
      surprising to find growth disorders associated with zinc deficiency. Stunted
      growth linked to zinc deficiency is found during gestation, and also in the
      newborn and children up to adolescence. Depending on the country, 5-30% of
      children suffer from moderate zinc deficiency, responsible for small-for-age
      height. Zinc supplementation has proven effective in many studies, mainly in
      children where zinc deficiency has first been found. Finally, zinc
      supplementation makes it possible in certain cases to overcome resistance to
      growth hormone treatment.

PMID- 1375078
TI  - The role of zinc in reproduction. Hormonal mechanisms.
AB  - Zinc is a very important element in the reproductive cycle of species. In humans,
      it is necessary for the formation and maturation of spermatozoa, for ovulation,
      and for fertilization. During pregnancy, zinc deficiency causes a number of
      anomalies: spontaneous abortion, pregnancy-related toxemia, extended pregnancy or
      prematurity, malformations, and retarded growth. Delivery is adversely affected
      by deficiency. These different effects of zinc can be explained by its multiple
      action on the metabolism of androgen hormones, estrogen and progesterone,
      together with the prostaglandins. Nuclear receptors for steroids are all zinc
      finger proteins. Zinc supplementation has already proven beneficial in male
      sterility and in reducing complications during pregnancy. However, it would be
      worth conducting larger-scale trials to confirm these beneficial effects.

PMID- 1375081
TI  - Serum zinc and somatic growth in children with growth retardation.
AB  - A possible role for zinc deficiency in some cases of growth retardation in
      southern France was investigated. Control values for zinc for 160 children (age =
      12.5 +/- 2.4 yr) are 0.85 +/- 0.22 mg/L (mean +/- 2 SD). Twenty-five children
      with low serum zinc values (less than 0.63 mg/L) and 25 matched short children
      with normal serum zinc values (greater than 0.63 mg/L) were studied. Children in
      the two groups did not differ significantly in age, pubertal development,
      stature, and weight. For the 25 children whose serum values were low, we found
      significantly lower values for bone age delay, growth velocity in mm/month, as
      well as the ratio between calculated growth velocity and theoretical growth
      velocity for the bone age (so that zincemia was correlated to these parameters in
      the whole sample of 50 subjects). Nevertheless, no significant difference could
      be found between the two groups for serum somatomedin C, serum osteocalcin
      values, and GH responses to the GH stimulatory tests (exercise test, overnight
      sampling, insulin-induced hypoglycemia, arginine test). Therefore, low serum zinc
      is associated with a retardation in both somatic growth and pubertal maturation.

PMID- 1375082
TI  - Effects of a multivitamin mineral supplement on zinc and copper status during
      pregnancy.
AB  - The effect of a multivitamin-mineral supplement was investigated during pregnancy
      according to a double-blind protocol by determining zinc and copper in maternal
      plasma, mononuclear and polynuclear zinc and copper at the third, sixth, eighth,
      and ninth months of gestation. The subjects were supplemented from the first
      trimester until delivery. A significant decrease was observed in plasma zinc that
      varied from 11.5 mumol/L to 10.8 mumol/L in the supplemented group (n = 29) and
      from 11 mumol/L to 10 mumol/L in the placebo group (n = 33) at 3 and 9 mo of
      gestation, respectively. In contrast, plasma copper levels increased in a way
      depending upon the stage of gestation in both groups: from 24.7 to 28.2 mumol/L
      in the treated group and from 24.9 to 30.9 mumol/L in the placebo group at 3 and
      9 mo of gestation, respectively, but the difference was only significant in the
      placebo group. No difference between groups was observed in mononuclear and
      polynuclear zinc or copper levels. These trace elements were also determined in
      cord blood at delivery. There were no statistically significant differences in
      zinc and copper concentration found in placebo group and supplemented group.
      Finally, the beneficial effect of supplementation on muscular cramps and
      appearance of vergetures was noted.

PMID- 1375084
TI  - Interleukin 2 production in iron-deficient children.
AB  - The relationship between iron status and capacity for IL-2 production by
      lymphocytes was assessed in 81 children from 6 mo to 3 yr of age selected at
      random from a population with low socioeconomic status, undergoing free
      systematic examination in four children's health centers in the Paris area. Iron
      deficiency was defined by the existence of at least two abnormal values among the
      three indicators of iron status: serum ferritin level less than or equal to 12
      micrograms/L, transferrin saturation less than 12%, and erythrocyte
      protoporphyrin concentration greater than 3 micrograms/g hemoglobin. According to
      this definition, 53 children were classified as iron deficient and 28 as iron
      sufficient. No differences were observed between the iron-deficient and iron
      sufficient groups in terms of the IL-2 concentration without stimulation by PHA.
      IL-2 production by lymphocytes stimulated with PHA, as well as the stimulation
      index (ratio of IL-2 concentration following stimulation by PHA to that of IL-2
      concentration without stimulation by PHA) were significantly lower in iron
      deficient children. The reduction in IL-2 production by activated lymphocytes
      observed in our study of iron-deficient children may be responsible for
      impairments in immunity found by other authors, particularly in cell-mediated
      immunity.

PMID- 1375083
TI  - The effect of barium selenate injection on selenium concentration and glutathione
      peroxidase activity in blood of pregnant ewes fed selenium-deficient diet.
AB  - Selenium (Se) levels in whole blood and plasma, and glutathione peroxidase (GSH
      Px) activities in red cells and plasma were measured in ewes fed an Se-deficient
      diet injected with barium selenate before breeding season. Highly significant
      increases in Se levels and GSH-Px activities (P less than 0.001) were observed
      throughout the gestation period and during lactation. In the control group, Se
      levels and GSH-Px activities decreased significantly (P less than 0.001), and
      were at critically low levels during lambing and lactation periods.

PMID- 1375085
TI  - Chromium status of full-term and preterm newborns.
AB  - In order to obtain reference values from normal babies, Cr status of full-term
      newborns has been studied. Plasma and urine values were (mean +/- SEM) 0.7 +/-
      0.1 micrograms/L and 0.9 +/- 0.3 micrograms/L, respectively, for the first month
      of life (n = 19), and 0.6 +/- 0.1 micrograms/L and 0.8 +/- 0.2 micrograms/L for
      the second-to-third-month period (n = 31). Premature newborns (gestational age 28
      36 wk) were compared to these control values; concentrations were 0.9 +/- 0.1
      micrograms/L and 1.1 +/- 0.2 micrograms/L for the first month (n = 47), and 1.0
      +/- 0.2 micrograms/L and 1.5 +/- 0.3 micrograms/L for the second to third months
      (n = 27). For the whole group, there was a positive correlation between plasma
      and urine concentrations (p = 0.0001); multiple regression analysis was performed
      between plasma levels and gestational age at birth (p = -0.002) and postnatal age
      (NS). Plasma levels of prematures and full terms were statistically different (p
      = 0.03) only for the second- to third-month period. It is suggested that these
      high Cr levels result from high dietary intakes and/or high absorption rates.

PMID- 1375086
TI  - Plasma chromium concentrations in normal infants and cystic fibrosis patients.
AB  - Plasma Cr concentrations have been studied in normal children aged 0-14 yr.
      Levels ranged from 0.65 to 0.88 microgram/l and did not change with age. Plasma
      concentrations of CF patients given 0.5-0.75 microgram Cr/kg/d in addition to
      their diet were similar to normal values. There was no correlation between these
      plasma values and growth retardation.

PMID- 1375087
TI  - The effect of chromium on parameters related to iron metabolism.
AB  - The effect of chromium on some parameters related to iron metabolism was
      investigated. Preliminary experiments showed that this metal ion was taken up by
      serum proteins and was dependent on the amount of chromium present in the medium.
      It was also shown that the uptake of iron was reduced significantly in the
      presence of chromium. In vivo study showed that the serum levels of iron and
      total iron binding capacity (TIBC) were reduced by 28 and 11%, respectively,
      following daily administration of chromium (1 mg/kg) for 45 d. Serum ferritin was
      reduced by 22% under this condition. Hematocrit and hemoglobin levels were also
      affected in chromium-treated animals and were both reduced by 17%.
      Spectrophotometric titration of each individual amino acid located in the iron
      binding site of transferrin revealed that tyrosine might be the most suitable
      ligand for the binding of chromium to transferrin. These results suggest that
      chromium may compete with iron in binding to apo-transferrin, and influence iron
      metabolism and its related biochemical parameters.

PMID- 1375088
TI  - Chromium metabolism. A literature review.
AB  - The trivalent state of chromium (Cr3+) is that encountered in biological milieus
      and is responsible for its nutritional activity. The principal route by which
      trivalent chromium enters the body is the digestive system. Chromium in foods is
      present both in the inorganic form and as organic complexes. Intestinal
      absorption of chromium is low (0.5-2%), and the mechanism has not yet been fully
      elucidated. Absorbed chromium circulates as free Cr3+, as Cr3+ bound to
      transferrin or other plasma proteins, or as complexes, such as glucose tolerance
      factor (GTF)-Cr. Circulating trivalent chromium can be taken up by tissues, and
      its distribution in the body depends on the species, age, and chemical form. It
      is excreted primarily in the urine by glomerular filtration or bound to a low-mol
      wt organic transporter. Chromium metabolism is still imperfectly understood. The
      use of 51Cr has nevertheless furnished valuable data concerning its transport and
      excretion.

PMID- 1375089
TI  - Chromium content in the hair of children and students in southern Poland.
AB  - Chromium concentrations in hair were compared in groups of children and students
      from Southern Poland. There were no statistically significant differences (at p
      greater than 0.05) between girls and boys. The results are similar to those found
      by other authors in different countries.

PMID- 1375090
TI  - Physiological chromium determination in serum by Zeeman graphite furnace atomic
      absorption spectrometry. A serious challenge.
AB  - Several authors have already underlined chromium implication in glucose and
      lipids metabolism of humans. In this field, physiological chromium determination
      in serum could be helpful, but the discrepancies reported in numerous papers are
      confusing. Here we report some results obtained by Zeeman correction Graphite
      Furnace Atomic Absorption Spectrometry. This technique includes a dilution of
      serum with 12.5 mM ultrapure nitric acid and 0.25% Triton X-100 (final
      concentrations). Some main features can be outlined: (1) the contamination
      constitutes a serious drawback and (2) the sensitivity of the technique is
      critical (characteristic mass found: 1.76 pg/0.0044 A.s). Our results obtained
      from 27 healthy subjects (2.01 +/- 0.77 nmol/L) agree with most recent studies
      and indicate that serum chromium level does not seem to be sex-related.

PMID- 1375091
TI  - Chromium content of foods and diets.
AB  - Comparatively few valid data are available on the chromium content of foods and
      on the dietary chromium (Cr) intake of various populations. This is chiefly
      because of the difficulties encountered in contamination control during sampling,
      sample pretreatment, and analysis. Moreover, there are several analytical
      problems involved that are mostly owing to the low concentration level of Cr in
      foods. However, with the recent establishment of food reference materials with
      certified low concentrations of Cr, the analytical validity of studies on Cr
      content of foods and on its dietary intake by various populations can be
      ascertained. With the exception of herbs and condiments, and certain other
      special food items with a relatively low average consumption rate, such as tea,
      coffee, and some candies, most foods contain Cr below 100 micrograms/kg. Staple
      foods, particularly cereals and milk, are very low (less than or equal to 10
      micrograms/kg) in Cr, showing little or no geographic variation. Food processing
      may increase food Cr content depending on the process. Processes, such as meat
      grinding and homogenization using stainless-steel equipment, very strongly
      increase the Cr content of foods. Also, acidic fruit juices in contact with steel
      cans are high in Cr, whereas cooking in aluminium vessels reduces the Cr content
      of foods. Average dietary Cr intake seems to fluctuate considerably among
      countries. In many developing countries, such as Brazil, the Sudan, and Iran, the
      dietary intake is high, from 50-100 micrograms/d, whereas in certain developed
      countries, such as Finland, Sweden, Switzerland, and the US, the intake is 50
      micrograms/d or lower and, consequently, at or below the estimated safe and
      adequate daily dietary intake range of 50-200 micrograms/d established by the US
      National Academy of Sciences. The average Cr content of human milk is below 0.5
      micrograms/L, thus resulting in a very low average intake of 0.3 microgram Cr/d
      by exclusively breast-fed infants in the US and Finland.

PMID- 1375093
TI  - Treatment and planning decisions in non-small cell carcinoma of the lung: an
      Australasian patterns of practice study.
AB  - Fourteen practising radiation oncologists were surveyed to assess their treatment
      and planning habits utilizing six sample cases of non-small cell carcinoma of the
      lung. Respondents were first given a general questionnaire, designed to evaluate
      their theoretical treatment and planning recommendations based on various tumour
      and patient related variables. Respondents then undertook a practical planning
      exercise utilizing planning CT and simulator radiographs for each of the six
      sample cases. Each case was accompanied by a brief history and report outlining
      specific tumour stage and non-stage related variables. The practical planning
      exercise was repeated on the second day of the survey utilizing different non
      stage related variables but identical radiology and stage-related information.
      This design enabled firstly, a comparison of clinicians' intended policy and
      planning methods with actual policy and planning decisions, and secondly, an
      assessment of intra-clinician variability in decision making and planning
      practice. Good agreement was evident among clinicians with respect to general,
      non-case specific treatment policies; however, very significant variation
      occurred at an inter- and intra-clinician level and involved the entire treatment
      and planning process for individual cases. Despite identical treatment intent
      across identical radiological case pairings, clinicians chose widely differing
      margins and target volumes in their planning exercise. Treatment intent appeared
      to be influenced more by non-stage related variables rather than stage related
      information and radiological appearances per se. We have shown that experienced
      radiation oncologists do not adhere to stated case selection criteria and show
      inconsistencies in their treatment planning for non-small cell carcinoma of the
      lung.

PMID- 1375092
TI  - Theoretical study of the intake of trace elements (nutrients and contaminants)
      via total diet in some geographical areas of Spain.
AB  - The aim of this study was to monitor exposure to heavy metal contaminants from
      habitual diets and to estimate the health risk for the consumer by comparing the
      analyzed content with the acceptable daily intake (ADI). This study is based on
      the household consumption as assessed by the National Institute of Statistics
      (INE) and our department. The number of food groups (237) consumed by the
      population (national and the 17 Autonomy Communities) is considered. A list of
      the metal content of foods in included. The data were collected from reports
      issued by the Ministry of Health, other official organizations, and from
      specialized literature. The results show that the intakes of arsenic (0.019
      mg/person/d), mercury (0.004 mg/person/d), and lead (0.082 mg/person/d) do not
      reach the ADI, but that of cadmium exceeds the ADI in some geographical areas.
      The intake of zinc and chromium does not exceed the dietetic recommendations.

PMID- 1375095
TI  - Segregated thalamocortical pathways to inferior parietal and inferotemporal
      cortex in macaque monkey.
AB  - Inferior parietal and inferotemporal cortex, which process different aspects of
      visual information through largely segregated pathways from the visual cortex,
      both receive thalamic afferents from the pulvinar complex. We examined the
      topography of pulvinar projections to these two cortical regions by placing
      multiple injections of different tracers (fluorescent dyes, horseradish
      peroxidase) in the inferotemporal and inferior parietal cortex of macaque
      monkeys. The patterns of label observed after injections in inferotemporal gyrus
      indicate that area TEO and the ventral part of area V4 receive a major input from
      the ventral part of the lateral pulvinar (PuLv) while area TE has strong
      connections with the caudal pole of the medial pulvinar (PuM) and only minor
      connections with PuLv. In contrast, injections in the caudal inferior parietal
      cortex demonstrate that area PGc, on the lateral surface of the inferior parietal
      gyrus, and area POa, in the ventral bank of intraparietal sulcus, receive strong
      projections from PuM and the adjacent fringe of the dorsal part of the lateral
      pulvinar (PuLd). Paired injections of two different tracers in the inferotemporal
      and inferior parietal cortex of the same hemisphere revealed a nearly complete
      segregation of the two populations of labeled neurons in the pulvinar, with only
      a small region of overlap in PuM, close to the PuM/PuLd border. These results
      demonstrate a clear separation of the thalamic afferents to the inferior parietal
      and inferotemporal cortex which parallels the separation of prestriate afferents
      to these two cortical territories (Morel & Bullier, 1990).

PMID- 1375094
TI  - Samarium-153-labelled EDTMP for bone metastases from cancer of the prostate.
AB  - A Phase I dose-escalation trial of a bone seeking phosphonate labelled with
      Samarium-153 was conducted on heavily pretreated patients with widespread bony
      metastases from cancer of the prostate. The bone marrow dose was calculated
      initially on a 4:1 uptake of cortical to cancellous bone, but subsequent
      information suggested the distribution was approximately equal so that the marrow
      received about three times the dose that has been prescribed. As a result, what
      were at first thought to be doses of 0.5 Gy, 1.0 Gy and 1.5 Gy were probably 1.5
      Gy, 3.0 Gy and 4.5 Gy respectively. Three patients were treated at each dose
      level. The dose was repeated in the first three. Pain relief was delayed for 2
      weeks, and was maximal by 4 weeks. All but one patient gained some benefit but
      this was transitory, lasting only 4-6 weeks in most. A recalculated dose of 3 Gy
      proved the most effective. The major toxicity was to platelets. Thrombocytopenia
      was fatal in four cases (two with repeat doses). All patients died but three
      survived more than 6 months with the help of third line hormonal measures and
      local radiotherapy to maintain comfort. A second group of five patients, not
      previously irradiated, were given 153Sm-EDTMP to a marrow dose of 3 Gy and all
      have survived for more than 4 months and achieved minimal to excellent relief of
      pain. The technique is recommended as initial therapy in unirradiated patients
      with good bone marrow function and with significant pain above and below the
      diaphragm, making half-body irradiation less likely to be a useful palliative
      procedure.

PMID- 1375096
TI  - Ocular dominance columns in area 17 of Old World macaque and talapoin monkeys:
      complete reconstructions and quantitative analyses.
AB  - The effects of monocular deprivation on cytochrome-oxidase (CO) expression were
      used to reveal ocular dominance columns in flatmounts of the striate cortex in
      macaque (Macaca fascicularis) and talapoin (Miopithecus talapoin) monkeys. This
      procedure allowed the first direct visualization of the complete pattern of
      ocular dominance bands in macaque monkeys, and less complete reconstructions in
      talapoin monkeys. In a second macaque monkey, the ocular dominance organization
      was revealed by injecting wheat germ agglutinin conjugated to horseradish
      peroxidase (WGA-HRP) into one eye. The organization of ocular dominance columns
      in the macaque monkeys conforms to previous descriptions, but the flat-mounted
      hemispheres provide accurate details on (1) the arrangement of columns, (2) the
      orientation of the representation of the optic disc, and (3) the breakdown of the
      bands in the cortex between the optic disc and monocular representations into a
      pattern of dots activated by the ipsilateral eye and larger surrounds related to
      the contralateral eye. Talapoin monkeys, the smallest of Old World monkeys, have
      sharply segregated ocular dominance bands. The columns in talapoins are narrower
      than those in macaques, so that even with less striate cortex than macaques,
      talapoins have more ocular dominance hypercolumns.

PMID- 1375097
TI  - Substance P modulates calcium current in retinal bipolar neurons.
AB  - Retinal bipolar cells are non-spiking interneurons that relay information from
      photoreceptors to amacrine and ganglion cells. In turn, bipolar cells receive
      extensive synaptic feedback from amacrine cells, some of which contain
      neuropeptides, including substance P. We have examined the effect of substance P
      on single bipolar neurons isolated from goldfish retina and find that substance P
      (0.1-1 nM) produced a voltage-dependent inhibition of calcium current in these
      cells. The inhibition was strongest at negative potentials, with the peak
      suppression occurring at -20 to -30 mV; at potentials positive to 0 mV, there was
      little effect on calcium current. Thus, the net effect was to shift the voltage
      range of activation of calcium current toward more positive potentials. The
      inhibition of calcium current by substance P required GTP in the patch pipette
      and was blocked by internal GDP-beta-S. Similar effects on calcium current were
      observed with somatostatin and metenkephalin, which are also found in amacrine
      cells.

PMID- 1375098
TI  - [3H]iloprost and prostaglandin E2 compete for the same receptor site on cardiac
      sarcolemmal membranes.
AB  - We have previously demonstrated that high-affinity PGE receptors are present on
      purified cardiac sarcolemmal (SL) membrane from bovine heart (Lopaschuk et al.
      (1989) Circ. Res. 65, 538-545). In this study we determined whether PGI2
      receptors are also present on the cardiac SL membrane. Due to the extreme
      lability of prostacyclin (PGI2) under physiological conditions, the PGI2
      analogue, Iloprost was substituted for PGI2. 3H-Iloprost specifically bound to
      two sites on the SL membrane; one of high affinity (Kd = 0.3 nM, Bmax = 97.0
      fmol/mg SL), and one of lower affinity (Kd = 20.6 nM, Bmax = 1589 fmol/mg SL).
      Competition studies demonstrated that the concentrations of PGE2 and PGE1
      necessary to displace 50% of the specific binding of 20 nM [3H]Iloprost on
      cardiac SL were 15-fold lower than the concentrations of unlabelled Iloprost
      necessary to displace 50% of binding. In contrast, a 15-fold higher concentration
      of unlabelled Iloprost was needed to displaced 50% of specific binding of 2 nM
      [3H]PGE2 compared to the concentrations of PGE1 or PGE2 required to displace 50%
      of [3H]PGE2 binding. In summary, our results indicate that a prostacyclin
      receptor is present on the cardiac sarcolemmal membrane, and that PGI2 competes
      for the same receptor site as PGE2.

PMID- 1375100
TI  - Effects of temperature variation and phenethyl alcohol addition on acyl chain
      order and lipid organization in Escherichia coli derived membrane systems. A 2H-
      and 31P-NMR study.
AB  - Using 2H- and 31P-NMR techniques the effects of temperature variation and
      phenethyl alcohol addition were investigated on lipid acyl chain order and on the
      macroscopic lipid organization of membrane systems derived from cells of the
      Escherichia coli fatty acid auxotrophic strain K1059, which was grown in the
      presence of [11,11-2H2]oleic acid. Membranes of intact cells showed a gel to
      liquid-crystalline phase transition in the range of 4-20 degrees C, which was
      similar to that observed for the total lipid extract and for the dominant lipid
      species phosphatidylethanolamine (PE). Phosphatidylglycerol (PG) remained in a
      fluid bilayer throughout the whole temperature range (4-70 degrees C). At 30
      degrees C acyl chain order was highest in PE, followed by the total lipid
      extract, PG, intact cells, and isolated inner membrane vesicles. Acyl chain order
      in E. coli PE and PG was much higher than in the corresponding
      dioleoylphospholipids. E. coli PE was found to maintain a bilayer organization up
      to about 60 degrees C, whereas in the total lipid extract as well as in intact E.
      coli cells bilayer destabilization occurred already at about 42 degrees C. It is
      proposed that the regulation of temperature at which the bilayer-to-non-bilayer
      transition occurs may be important for membrane functioning in E. coli. Addition
      of phenethyl alcohol did not affect the macroscopic lipid organization in E. coli
      cells or in the total lipid extract, but caused a large reduction in chain order
      of about 70% at 1 mol% of the alcohol in both membrane systems. It is concluded
      that while both increasing temperature and addition of phenethyl alcohol can
      affect membrane integrity, in the former case this is due to the induction of non
      bilayer lipid structures, whereas in the latter case this is caused by an
      increase in membrane fluidity.

PMID- 1375099
TI  - Effect of cell exposure to top or bottom phase prior to cell partitioning in
      dextran-poly(ethylene glycol) aqueous phase systems: erythrocytes as a model.
AB  - Cells exposed to dextran (Dx)-rich bottom phase prior to cell partitioning in Dx
      poly(ethylene glycol) (PEG) aqueous two-phase systems have lower partition ratios
      than cells exposed to PEG-rich top phase. Aspects of this previously observed
      phenomenon were explored. In the present work charge-sensitive phases made with
      Dx T500 and PEG 8000 were used exclusively. It was found that: (1) even on
      countercurrent distribution (CCD) red cells (RBC) loaded in bottom phase have a
      lower apparent partition ratio, G, than the same cells loaded in top phase; (2)
      when part of the same cell population is loaded into top phase and part into
      bottom phase of the same load cavities for CCD, with the cells loaded into top or
      bottom bearing an isotopic tracer (51Cr), the cells loaded into top phase have a
      higher G value than the cells loaded into bottom phase; (3) the shift in the CCD
      curves of human or of rat RBC between cells loaded in top or bottom phase using
      systems having the same polymer concentration (though different salt
      compositions) shows no striking difference and is, for the number of experiments
      run, not statistically significant; (4) when the quantity of cells loaded for CCD
      is reduced from 10(9) to 10(8), the G value of cells loaded in top phase is
      reduced slightly while that of cells loaded in bottom phase is diminished more
      appreciably; (5) increasing polymer concentrations yield larger differences in G
      values between (rat) RBC loaded in top or bottom phase; (6) when cells exposed to
      top or bottom phase, respectively, are centrifuged and suspended in bottom or top
      phase, respectively, their CCD patterns are qualitatively similar to cells
      exposed to these latter respective phases initially; (7) rat RBC populations
      containing 59Fe-labeled cells of different but distinct age are fractionated on
      CCD irrespective of whether loaded in top or bottom phase. An exception are
      populations containing very young mature labeled cells (e.g., 4-d old) which are
      resolved when loaded in top phase but not in bottom phase. Thus cell populations
      exist which can be resolved by CCD when loaded in one of the phases but not when
      loaded in the other. Glutaraldehyde-fixed rat RBC containing 4-d old labeled
      cells are fractionated by CCD irrespective of whether loaded in top or bottom
      phase.

PMID- 1375102
TI  - Hydroxyurea: specific therapy for sickle cell anemia?

PMID- 1375101
TI  - Permeabilizing action of filipin III on model membranes through a filipin
      phospholipid binding.
AB  - The binding of the pentaene antibiotic filipin to egg-yolk phosphatidylcholine
      (EPC) and dimyristoylphosphatidylcholine (DMPC) unilamellar vesicles, has been
      studied by ultraviolet (UV) absorption and circular dichroism (CD). A
      stoichiometry of one molecule of filipin for five molecules of phospholipid was
      demonstrated by CD when phospholipids were in fluid phase. The similarity of the
      CD spectra with EPC and DMPC established a similar filipin-phospholipid
      assemblage in both membranes. We therefore postulated that filipin incorporation
      leads to the formation of gel-like domains in fluid EPC membranes as previously
      demonstrated for fluid DMPC membranes (Milhaud, J., Mazerski J., Bolard, J. and
      Dufoure, E.J. (1989) Eur. Biophys. J. 17, 151-158). The release of fluorescent
      probes (carboxyfluorescein (CF) or calcein (CC)), entrapped in EPC small
      unilamellar vesicles (SUV), due to the action of filipin, was followed by
      fluorescence and CD measurements concomitantly. The following observations were
      made. (1) The percentage of released probe, as a function of the
      filipin/phospholipid molar ratios, was the same whether or not membranes
      contained cholesterol. (2) The permeabilization of vesicles proceeded
      concomitantly with filipin-phospholipid binding while filipin-cholesterol binding
      leveled off. (3) The release of the content of vesicles occurred by an all-or
      none mechanism leaving the depleted vesicles intact. From these observations and
      from the previous structural findings, a new interpretation of the action of
      filipin is proposed. Precluding any disruptive effect, inducement of permeability
      would result from the high intrinsic permeability of the interfacial region at
      the boundaries of the gel-like domains corresponding to the filipin-phospholipid
      aggregates. Additionally, we obtained the permeability coefficients for the
      anionic forms of CC and CF across EPC SUV, 0.6.10(-10) cm s-1 and 2.10(-10) cm s
      1, respectively, as compared to 2.5.10(-14) cm s-1 for the counterion Na+
      (Hauser, H, Oldani, D. and Phillips, M.C. (1973) Biochemistry 12, 4507-4517).

PMID- 1375103
TI  - Abnormal responsiveness of granulocyte-committed progenitor cells in cyclic
      neutropenia.
AB  - The mechanism(s) driving cyclic hematopoiesis in human cyclic neutropenia remains
      unknown. Clinical trials suggest that an abnormal responsiveness of bone marrow
      progenitor cells to hematopoietic growth factors might cause oscillatory blood
      counts. Studies were performed to determine whether an abnormal responsiveness to
      multiple growth factors exists in this disorder and whether the defect could be
      shown in highly enriched populations of marrow progenitor cells. Bone marrow
      mononuclear cells from patients with congenital cyclic neutropenia required
      higher concentrations of added granulocyte-colony-stimulating factor (G-CSF) to
      achieve half-maximal colony growth than cells from normal subjects (478 +/- 90
      pmol/L v 53 +/- 12 pmol/L, P less than .01). Patients also differed in
      requirement for granulocyte-macrophage-CSF (P less than .05), but not for
      interleukin-3 (P greater than .30). CD34+ bone marrow cells from three patients
      also showed this difference in G-CSF responsiveness (P less than .05). These data
      suggest that the defect in congenital cyclic hematopoiesis lies in growth factor
      receptor binding or the postreceptor signal transduction system that drives
      granulocytopoiesis.

PMID- 1375104
TI  - Hydroxyurea: effects on hemoglobin F production in patients with sickle cell
      anemia.
AB  - Patients with sickle cell anemia were treated with daily doses of hydroxyurea, to
      assess pharmacokinetics, toxicity, and increase in fetal hemoglobin (Hb)
      production in response to the drug. Plasma hydroxyurea clearances were not a
      useful guide to maximum tolerated doses of the drug. The mean daily single oral
      dose that could be maintained for at least 16 weeks was 21 mg/kg (range, 10 to 35
      mg/kg). Among 32 patients, last HbF levels were 1.9% to 26.3% (mean, 14.9%) with
      increases in HbF over initial values of 1.4% to 20.2% (mean, 11.2%). The most
      significant predictors of last HbF were last plasma hydroxyurea level, initial
      white blood count and initial HbF concentration. Last HbF was not related to beta
      globin haplotype or alpha globin gene number. No serious toxicity was
      encountered. Clinically significant bone marrow depression was avoided, and
      chromosome abnormalities after 2 years of treatment were no greater than those
      observed before treatment. The period of observation has been too short to
      evaluate the risk of carcinogenesis. Patient's red cells developed striking
      macrocytosis. Median red cell Hb concentrations did not change. Hb concentrations
      increased, on average 1.2 g/dL, but serum erythropoietin levels increased.
      Patients' body weights increased, and some returned to work or school, but no
      conclusions regarding therapeutic efficacy could be drawn from this uncontrolled
      open-label study.

PMID- 1375105
TI  - Decreased expression of eosinophil peroxidase and major basic protein messenger
      RNAs during eosinophil maturation.
AB  - We evaluated the levels of mRNAs encoding cationic proteins in peripheral blood
      eosinophils (PBE) purified from patients with eosinophilia and in eosinophils
      differentiated from cord blood cells (CBC) by culture with recombinant human
      interleukin-3 (rhIL-3), rhGM-CSF, and rhIL-5. Messenger RNAs encoding eosinophil
      peroxidase (EPO), major basic protein (MBP), eosinophil-derived neurotoxin (EDN),
      and eosinophil cationic protein (ECP) were detected by Northern blot
      hybridization with the respective specific oligonucleotide probes. In mature PBE,
      MBP mRNA appeared to be absent, whereas EPO mRNA was barely detectable in only 5
      of the 19 patients. In contrast, EDN and ECP mRNAs were observed in the PBE of
      all patients. In CE, EPO, and MBP, mRNAs were abundant in immature eosinophils
      and their amounts decreased after differentiation toward eosinophils. ECP and EDN
      mRNAs followed the same patterns, but mRNAs were less abundant at all timepoints
      studied. Study of mRNA t1/2 during the time course of differentiation indicated
      that changes in the stability of the different mRNAs were not responsible for the
      variations observed in the steady-state levels. Together, these results suggest
      that regulation of expression differs among EPO, MBP, EDN, and ECP mRNAs during
      the time course of eosinophil differentiation.

PMID- 1375106
TI  - Long-term generation of colony-forming cells in liquid culture of CD34+ cord
      blood cells in the presence of recombinant human stem cell factor.
AB  - Human cord blood was used as a source of progenitor and stem cells to evaluate
      the effect of recombinant human stem-cell factor (SCF) on colony formation and
      the generation of colony-forming cells (CFC) under highly defined, serum-deprived
      conditions. SCF interacted with a number of hematopoietic growth factors to
      stimulate colony growth and was particularly effective in stimulating the
      formation of mixed-cell colonies from CD34+ soybean agglutinin negative (SBA-)
      cells. In suspension culture of CD34+, SBA- cells, SCF alone was unable to
      maintain cell numbers or CFC but, in combination with interleukin-3 (IL-3),
      increased input numbers of cells by 10-fold and increased CFC of all kinds by
      nearly 20-fold. This included erythroid burst-forming cells (BFU-E),
      granulocyte/macrophage (GM) CFC, and mixed-cell CFC. In contrast, CD34- SBA-
      cells neither gave rise to CFC nor were maintained by combinations of growth
      factors including SCF. SCF interacted with erythropoietin (Epo) and granulocyte
      colony-stimulating factor (G-CSF) to maintain large numbers of cells as well as
      to generate a twofold to threefold increase in CFC in the case of Epo, and a 10
      fold increase in CFC in the case of G-CSF. With Epo, the predominant CFC
      generated were BFU-E and erythroid CFC and many of the cells in suspension were
      erythroblasts. In contrast, SCF plus G-CSF resulted in large numbers of
      granulocytes at various stages of maturation and the CFC generated were almost
      exclusively granulocytic-CFC. IL-1 and IL-6, alone or in combination with SCF,
      showed little or no ability to increase cell numbers or generate CFC. In summary,
      SCF interacts with a variety of hematopoietic growth factors to promote colony
      formation, particularly mixed-cell colony formation, and also, in suspension
      culture, SCF interacts with IL-3, G-CSF, and Epo to generate large numbers of
      differentiated cells as well as a variety of CFC for up to 1 month.

PMID- 1375107
TI  - Interferon-gamma enhances factor-dependent myeloid proliferation of human CD34+
      hematopoietic progenitor cells.
AB  - Numerous studies have shown that interferon-gamma (IFN gamma) inhibits the
      proliferative effects of colony-stimulating factors (CSFs) on human bone marrow
      cells. In the present study we investigated the effects of IFN gamma and other
      described inhibitory factors on the proliferation of highly purified CD34+ human
      hematopoietic progenitor cells (HPC) in response to recombinant CSFs. While
      transforming growth factor-beta (TGF beta) and IFN alpha were highly inhibitory,
      IFN gamma strongly potentiated interleukin-3 (IL-3) and, to a lesser extent,
      granulocyte-macrophage-CSF (GM-CSF) induced growth of CD34+ HPC. IFN gamma had no
      significant proliferative effect per se, and did not affect granulocyte-CSF (G
      CSF)-dependent cell proliferation. Within 10 days the number of viable cells
      generated in the presence of IL-3 + IFN gamma was two times higher than in the
      presence of IL-3 alone. Limiting dilution analysis showed that IFN gamma acts
      directly on its target cell to increase the frequency of IL-3-responding cells
      without affecting the average size of the IL-3-dependent clones. Enhanced
      frequency of IL-3- and GM-CSF-responding cells was also observed in colony assays
      where the addition of IFN gamma increased by twofold to threefold the number of
      granulocyte colony-forming units (CFU-G), macrophage CFUs (CFU-M), granulocyte
      macrophage CFUs (CFU-GM), and mixed erythroid (E-MIX). In contrast, IFN gamma did
      not affect the generation of erythroid burst-forming units (BFU-e) in such
      cultures. In longer-term culture, the combination of IFN gamma and IL-3 did not
      alter the lineage distribution of the cells when compared with IL-3 alone.
      However, after 15 days, when mature cells were present in the cultures, IFN gamma
      displayed cell concentration-related growth-inhibitory effects. Thus, IFN gamma
      appears to stimulate the early stage of myelopoiesis by enhancing the frequency
      of growth factor-responding cells but, unlike tumor necrosis factor alpha (TNF
      alpha), does not alter cell differentiation.

PMID- 1375108
TI  - Plasminogen activator inhibitor-1 messenger RNA expression is induced in rat
      hepatocytes in vivo by dexamethasone.
AB  - Plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of
      tissue plasminogen activator (tPA), plays a crucial role in the regulation of
      fibrinolysis. Both hepatocytes and endothelial cells have been implicated as
      major sources of plasma PAI-1. To study the relative contribution of these cell
      types to hepatic PAI-1 production, we have separated hepatocytes and hepatic
      sinusoidal endothelial cells by fractionation of freshly isolated rat livers
      using metrizamide density gradients and centrifugal elutriation. In untreated
      animals, PAI-1 messenger RNA (mRNA) was detected only in the purified endothelial
      cell fraction, and not in the hepatocyte fraction or in unfractionated liver.
      However, when the animals were treated with dexamethasone, PAI-1 mRNA expression
      was transiently induced in the liver. This induction paralleled the appearance of
      PAI-1 mRNA in purified hepatocytes, while PAI-1 expression in sinusoidal
      endothelial cells was unchanged. Four hours after dexamethasone treatment, plasma
      PAI-1 levels were increased approximately twofold over levels measured in animals
      treated with the diluent alone. These data suggest that PAI-1 production by
      hepatocytes may contribute to elevated plasma PAI-1 levels in the setting of
      acute injury and stress.

PMID- 1375109
TI  - In vivo efficacy of B43 (anti-CD19)-pokeweed antiviral protein immunotoxin
      against BCL-1 murine B-cell leukemia.
AB  - We show that a highly aggressive subclone of murine BCL-1 B-lineage leukemia
      expresses a single 2.4-kb transcript hybridizing to the human CD19 cDNA probe and
      reacts strongly with the anti-human CD19 monoclonal antibodies (MoAb) B43, B4,
      Leu-12, and J3-119. In contrast to their strong reactivity with anti-human CD19
      MoAb, BCL-1 cells show no reactivity with MoAb directed against human CD22, CD72,
      HLA-DR, IgD, or IgM. Western blot analysis of BCL-1 whole cell lysates with the
      anti-human CD19 MoAb J3-119 showed a single 69-Kd protein band, which was not
      detected by the negative control MoAb G19.4 (anti-CD3). In contrast to BCL-1
      cells, normal BALB/c splenocytes or mouse splenocyte/myeloma hybridoma cell lines
      did not (1) express any transcripts that hybridized to the human CD19 cDNA probe,
      (2) react with B43/anti-CD19 MoAb, or (3) express the 69-Kd protein that reacts
      with the anti-human CD19 MoAb J3-119. Murine BCL-1 B-cell leukemia thus provides
      a unique model of disseminated B-lineage leukemia to evaluate the antileukemic
      efficacy of anti-CD19 immunotoxins. This model was subsequently used to evaluate
      the in vivo homing ability, pharmacokinetics, and antileukemic efficacy of B43
      MoAb conjugated to the plant hemitoxin pokeweed antiviral protein (PAP). B43-PAP
      immunotoxin (1) showed strong and antigen-specific reactivity with BCL-1 cells,
      (2) promptly penetrated the spleens of leukemic mice, (3) rapidly reduced the BCL
      1 leukemia burden of leukemic mice and, most importantly, (4) improved survival.
      Finally, B43-PAP immunotoxin was more effective against BCL-1 leukemia than 700
      cGy (LD100/30) total body irradiation (TBI) followed by syngeneic bone marrow
      transplantation (BMT).

PMID- 1375110
TI  - Impaired in vitro growth of purified (CD34+) hematopoietic progenitors in human
      immunodeficiency virus-1 seropositive thrombocytopenic individuals.
AB  - In this report the role played by human immunodeficiency virus type-1 (HIV-1) in
      the pathogenesis of HIV-1-related thrombocytopenia was investigated. CD34+
      hematopoietic stem/progenitor cells were purified from the bone marrow (BM) of
      HIV-1(+) thrombocytopenic patients, HIV-1(+) nonthrombocytopenic individuals, HIV
      1(-) patients with immune thrombocytopenic purpura, and HIV-1(-) normal donors.
      CD34+ cells from HIV-1(+) thrombocytopenic individuals alone showed a reduced
      capacity to give rise to megakaryocytic colonies (CFU-Meg) and also a progressive
      and significant decline in cell number when placed in liquid culture containing
      recombinant human interleukin-3 (rIL-3). This decline involved not only
      megakaryocyte but also erythroid and granulocyte/macrophage progenitors. The
      defects in megakaryocyte colony formation and CD34+ cell growth did not result
      from a productive HIV-1 infection of CD34+ cells. Moreover, HIV-1 DNA was absent
      from CD34+ cells in 10 of 12 thrombocytopenic patients examined. On the other
      hand, the decreased survival/proliferation of CD34+ cells in liquid culture,
      within the HIV-1(+) thrombocytopenic patients, was correlated with the presence
      of HIV-1 p24 antigen in BM plasma. These results demonstrate an impairment of
      CD34+ cells in HIV-1(+) individuals presenting thrombocytopenia as the only
      hematologic manifestation. Furthermore, these findings suggest that increased
      viral replication in the BM microenvironment may cause this impairment and
      possibly contributes to HIV-induced thrombocytopenia.

PMID- 1375111
TI  - Mutations of p53 gene and their relation to disease progression in B-cell
      lymphoma.
AB  - The alteration of p53 tumor suppressor gene was studied in 48 patients with B
      cell lymphoma. A sequential combined technique of polymerase chain reaction
      mediated single-strand conformational polymorphism (PCR-SSCP) or reverse
      transcription (RT)-PCR-SSCP and direct sequencing were used as a simple and
      sensitive approach to analyze nucleotide changes. By these methods, we identified
      8 missense point mutations and 2 codon deletions in 9 of the 48 patients. These
      mutations were located in or close to the evolutionally highly conserved regions
      of the p53 gene. Eight of nine patients having p53 gene alterations were in
      advanced clinical stage (IV). It is the first report of p53 gene mutations in
      follicular and diffuse lymphoma. These observations suggest that the p53 gene
      alteration may play an important role in lymphomagenesis and/or disease
      progression in some types of B-cell lymphoma.

PMID- 1375112
TI  - Cloning and analysis of a recombinant antigen containing an epitope specific for
      human T-cell lymphotropic virus type II.
AB  - An immunodominant HTLV-I-specific epitope in the HTLV-I envelope glycoprotein
      (GP) 46 has been described. To determine if the analogous region of HTLV-II
      contains a similarly immunogenic and specific epitope, the polymerase chain
      reaction (PCR) was used to amplify HTLV-II DNA fragments encoding various
      portions of the putative epitope. The synthesized DNAs were cloned into lambda
      phage gt11 and screened for production of immunoreactive fusion protein using
      sera from HTLV-II- or HTLV-I-infected individuals. Antisera from HTLV-II-infected
      individuals identified three of four recombinant clones when tested in a plaque
      immunoassay. Fusion protein from one of the clones, GH2-K15, was purified and
      analyzed by Western blot against a panel of HTLV-I and HTLV-II antisera. Twenty
      one of 22 HTLV-II-infected sera were reactive with the GH2-K15 epitope. Sera from
      HTLV-I-infected and HTLV-I-uninfected individuals did not cross-react with GH2
      K15. Western blot analysis of recombinant proteins encoding portions of the HTLV
      II sequences in the Gh2-K15 antigen localized the HTLV-II-specific epitope to a
      17-amino acid sequence. Recombinant antigens containing this epitope should be
      useful for type-specific serologic diagnosis of HTLV-II infection.

PMID- 1375113
TI  - Direct contact between human primitive hematopoietic progenitors and bone marrow
      stroma is not required for long-term in vitro hematopoiesis.
AB  - Long-term bone marrow cultures support both differentiation and conservation of
      primitive human hematopoietic progenitors in the absence of exogenous cytokines.
      It is believed that hematopoiesis in such cultures requires direct contact
      between hematopoietic progenitors and stroma. In the present study, we
      demonstrate that primitive progenitors physically separated from the stromal
      layer by a 0.45-microns microporous membrane continue to generate differentiated
      progenitors for at least 8 weeks. Moreover, primitive progenitors are conserved
      to a greater extent under these conditions, as when cultured in direct contact
      with the stroma. However, excessive production of granulocyte-macrophage
      progenitors occurs when primitive progenitors are not allowed to interact
      directly with the stroma. Thus, direct contact between hematopoietic and stromal
      cells is not required for either differentiation or conservation of primitive
      hematopoietic progenitors but is essential for the regulated production of mature
      blood elements. These findings can now be used to define the role of diffusible
      factors and cell-cell or cell-extracellular matrix adhesion events in the
      regulation of conservation, proliferation, and differentiation of primitive human
      hematopoietic progenitors in vitro.

PMID- 1375114
TI  - A diverged homeobox gene is involved in the proliferation and lineage commitment
      of human hematopoietic progenitors and highly expressed in acute myelogenous
      leukemia.
AB  - HB24 is a diverged homeobox gene known to be expressed in hematopoietic
      progenitor cells. We show here that the inhibition of HB24 expression in CD34+
      bone marrow cells via antisense (AS) oligonucleotides impaired the proliferation
      of these cells in response to interleukin-3 and granulocyte-macrophage colony
      stimulating factor. The treatment of CD34+ cells with HB24 AS oligonucleotides
      also reduced the levels of c-fos, c-myc, c-myb, cyclin B, and p34cdc2 messenger
      RNAs compared with cells treated with control oligonucleotides. Conversely, the
      transient transfection of HB24 into a subpopulation of CD34 cells inhibited their
      differentiation into mature hematopoietic cell types. In addition, HB24 messenger
      RNA transcripts were elevated in bone marrow and peripheral blood mononuclear
      cells isolated from patients with acute myelogenous leukemia compared with normal
      controls. These data suggest that HB24 is an important transcription factor
      during hematopoietic progenitor proliferation and that differentiation to
      specific cell types requires its downregulation. Furthermore, dysregulated
      expression of HB24 impairs the normal differentiation of hematopoietic
      progenitors and may contribute to leukemogenesis.

PMID- 1375115
TI  - Pharmacokinetics of subcutaneous recombinant human granulocyte colony-stimulating
      factor in children.
AB  - Fifteen children (age 1.2 to 9.4 years) with advanced neuroblastoma were treated
      with myelosuppressive chemotherapy (cyclophosphamide, cisplatin, doxorubicin)
      followed by 5 (n = 5), 10 (n = 5), or 15 (n = 5) micrograms/kg recombinant
      granulocyte colony-stimulating factor (rG-CSF) subcutaneously (SC) once daily for
      10 days, starting the day after chemotherapy. Serial serum samples obtained on
      days 1 and 10 were analyzed for G-CSF activity by a specific proliferation assay
      using NFS-60 cells. G-CSF serum concentration-time data were best described by a
      one-compartment model, with zero-order absorption and first-order elimination.
      After SC injection, absorption was prolonged, with peak concentrations of G-CSF
      (3 to 117 ng/mL) being reached after 4 to 12 hours. The relatively slow
      absorption, with a mean elimination half-life of 5.8 hours on day 1 and 4.5 hours
      on day 10, provided measurable G-CSF concentrations for the entire 24-hour dosing
      interval in all patients at each dosage level. The median apparent clearance of G
      CSF on day 10 was significantly higher than on day 1 (0.57 v 0.31 mL/min/kg, P =
      .02), and was positively correlated with the absolute neutrophil count (ANC) (r2
      = .33, P = .003). Systemic exposure to G-CSF was dose-related, but interpatient
      pharmacokinetic variability yielded overlap in area under the concentration-time
      curve (AUC) at all three dosage levels. Stepwise regression analysis showed that
      G-CSF AUC could be predicted by a model that includes rG-CSF dosage and ANC on
      the day of administration (r2 = .82, P = .0001).

PMID- 1375116
TI  - Enhancement of murine hematopoiesis by synergistic interactions between steel
      factor (ligand for c-kit), interleukin-11, and other early acting factors in
      culture.
AB  - Entry into the cell cycle of dormant hematopoietic progenitors appears to be
      regulated by multiple synergistic factors, including interleukin-6 (IL-6),
      granulocyte colony-stimulating factor (G-CSF), IL-11, and the ligand for c-kit,
      which is also known as steel factor (SF). We have tested the effects of these and
      other hematopoietic factors on the proliferation of partially enriched dormant
      murine progenitors in the presence and absence of serum. In serum-containing
      cultures, SF and IL-11 interacted to support the formation of multilineage
      colonies; the level of colony formation was comparable with the colony formation
      supported by other effective two-factor combinations. In serum-free cultures,
      colony formation supported by two factors was significantly less than that in
      serum-containing culture and the most effective two-factor combination in serum
      free culture was SF plus IL-3. In serum-free cultures, three-factor combinations
      consisting of SF, IL-3, and one of IL-6, G-CSF, or IL-11 yielded colony formation
      that was comparable with that seen in serum-containing cultures. These studies
      indicate that IL-11 belongs to a group of early-acting hematopoietic synergistic
      factors that now includes IL-6, G-CSF, and IL-11. In contrast, SF is unique among
      the synergistic factors in that it interacts either with growth factors such as
      IL-3 or GM-CSF or with synergistic factors such as IL-6, IL-11, or G-CSF.

PMID- 1375117
TI  - The clonal proliferation of normal mouse hematopoietic cells: enhancement and
      suppression by colony-stimulating factor combinations.
AB  - Combinations of relatively high concentrations of the four colony-stimulating
      factors (CSFs) in cultures of normal mouse bone marrow cells stimulated
      subadditive responses in the number of colonies developing but, with some
      combinations, superadditive increases in mean cell numbers per colony. This
      latter effect was due largely to the induced development of small numbers of
      giant colonies containing macrophages with or without granulocytes. However, in
      cultures including a combination of granulocyte-macrophage-CSF (GM-CSF) with
      macrophage-CSF (M-CSF), a selective reduction in the number of pure macrophage
      colonies was observed together with a change in the morphology of those colonies
      that did develop. Recloning studies on macrophage colonies showed that the
      inhibitory action of the GM-CSF plus M-CSF combination was a direct one on the
      colony cells. The example of inhibition observed suggests that combined
      stimulation by two positive growth factors can sometimes result in a selective
      reduction of the production of certain cells, a possibility needing further
      exploration.

PMID- 1375118
TI  - Granulocyte-macrophage colony-stimulating factor, interleukin-3, and steel factor
      induce rapid tyrosine phosphorylation of p42 and p44 MAP kinase.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF), Interleukin-3 (IL-3),
      and Steel Factor (SF) induce proliferation of hematopoietic cells through binding
      to specific, high-affinity, cell surface receptors. However, little is known
      about postreceptor signal transduction pathways. In previous studies, we noted
      that each of these three factors could independently support proliferation of the
      human MO7 cell line, and also that each factor induced a rapid increase in
      protein-tyrosyl phosphorylation. Although the proteins phosphorylated on tyrosine
      by GM-CSF and IL-3 are similar or identical in MO7 cells, many of the proteins
      that are phosphorylated on tyrosine after SF are different. However, two
      proteins, p42 and p44, were prominently phosphorylated in response to all three
      of the factors. In MO7 cells, the tyrosyl phosphorylation of p42 and p44 was
      transient, peaking at 5 to 15 minutes. In contrast to many of the other proteins
      which are tyrosyl phosphorylated in response to these factors, phosphorylation of
      p42 and p44 was temperature-dependent, occurring at 37 degrees C, but not at 4
      degrees C. We identified the p42 protein as p42 Mitogen-Activated Protein Kinase
      (p42mapk, ERK-2) and the p44 as a p42mapk-related protein using monospecific
      antisera to MAP kinase. GM-CSF, IL-3, and SF were each found to induce MAP kinase
      activity when assayed in vitro using myelin basic protein (MBP) as a substrate.
      Remarkably, we found that GM-CSF-induced tyrosyl phosphorylation of p42 and p44
      even in nonproliferative cells (neutrophils) that respond to this CSF, and that
      p42 and p44 were two of the most prominently tyrosyl phosphorylated proteins
      following GM-CSF stimulation of these cells. These results implicate p42mapk and
      p44 as important signal transducing molecules in myeloid cells, and it is likely
      that these kinases play a role as part of a sequential "kinase cascade" linking
      growth factor receptors to mitogenesis and other cellular responses.

PMID- 1375119
TI  - Regulation of complement functional efficiency by histidine-rich glycoprotein.
AB  - The modulation of complement functional efficiency by serum histidine-rich
      glycoprotein (HRG) was investigated. Addition of exogenous HRG to prewarmed
      diluted serum, followed immediately by sensitized sheep erythrocytes (EA),
      resulted in enhanced hemolysis. However, when HRG was incubated with diluted
      serum for 10 minutes at 37 degrees C, inhibition of hemolysis occurred. The
      biphasic modulation of complement function was also obtained with the complement
      alternative pathway when HRG was added to diluted serum for hemolysis of rabbit
      erythrocytes. Partial reduction of complement functional activity was shown when
      serum was absorbed by an HRG-Sepharose 6MB column. Western blot analysis showed
      that complement C8, C9, factor D, and S-protein in diluted serum were bound by
      nylon membrane-immobilized HRG. However, by immunoprecipitation of relatively
      undiluted serum with anti-HRG IgG beads, HRG was found to coprecipitate with S
      protein and plasminogen, which suggested that HRG may complex with these proteins
      in serum. In functional tests, HRG inhibited C8 hemolytic activity, probably by
      preventing C8 binding to EAC1-7 cells. HRG also enhanced polymerization of
      purified C9 as well as the generation of a 45-Kd C9 fragment. Such an effect was
      even more pronounced in the presence of divalent cations with the reaction
      mixtures of C9 and HRG. Partial dimerization of C9 was shown when exogenous HRG
      was added to normal serum. In contrast, polymerization of serum C9 was inhibited
      by exogenous HRG during poly I:C activation of serum or incubation under low
      ionic strength conditions. HRG was further shown to inhibit factor D-mediated
      cleavage of factor B when bound by cobra venom factor. The molecular basis by
      which HRG regulates serum complement function is not clear. Hypothetically, the
      tandem repetitions of a consensus histidine-rich penta-peptide sequence in HRG
      may provide a highly charged area that interacts with complement components.

PMID- 1375120
TI  - Growth- and differentiation-associated expression of bcl-2 in B-chronic
      lymphocytic leukemia cells.
AB  - The bcl-2 gene is translocated into the Ig loci in about 80% of human follicular
      lymphomas and in 10% of B-type chronic lymphocytic leukemias (B-CLL), resulting
      in a high level of expression. We have compared the expression of bcl-2
      transcripts and protein in B-CLL cells in their normal equivalent CD5+ B cells
      and in normal B-cell populations representative of different in vivo and in vitro
      stages of activation and proliferation. We report here that bcl-2 was expressed
      in 11 of 11 cases of CD5+ B-CLL clones, contrasting with the absent expression in
      normal CD5+ B cells. Activation of 173 and 183 B-CLL cells by phorbol esters (12
      O-tetradecanoylphorbol-13-acetate [TPA]) to IgM secretion without concomitant DNA
      synthesis resulted in a rapid but transient downregulation of bcl-2 expression.
      In contrast, the reduction of bcl-2 at both the messenger RNA and protein levels
      was sustained after mitogenic stimulation, suggesting that bcl-2 expression and
      proliferation are inversely related in these cells. This notion was further
      supported by immunocytochemical analysis showing that bcl-2 was primarily
      expressed in small resting lymphocytes and in cells differentiating to the plasma
      cell stage, but less expressed in Ki67-positive proliferating B blasts. Moreover,
      it was also supported by the low level of bcl-2 in exponentially growing Epstein
      Barr virus-carrying lymphoblastoid and B-CLL cell lines. The regulation of bcl-2
      expression in B-CLL resembled that of normal tonsillar follicular B cells, in
      which a high level of expression was found in resting mantle zone B cells but not
      in the proliferating germinal center B cells. Based on these findings and the
      role of bcl-2 in maintaining B-cell memory, we propose that the phenotype of B
      CLL cells corresponds to a mantle zone memory-type B cell.

PMID- 1375121
TI  - Complement activation during storage of blood under normal blood bank conditions.
      Effects of proteinase inhibitors and leukocyte depletion.
AB  - During storage of CPD-A1 preserved whole blood factors of the complement cascade
      become activated, as evidenced by a rapid increase in the concentrations of C3a
      desArg and C4a-desArg. After 10 to 14 days of whole blood storage, the elevations
      of C3a and C4a levels were highly significant. This increase was paralleled by an
      increase in the concentration of the lysosomal proteinase elastase from
      polymorphonuclear (PMN) granulocytes. By contrast, the concentration of the C3
      activator complex C4b2b remained unchanged even after 3 weeks of storage. The
      supplementation of the anticoagulant CPD-A1 with the polyvalent-proteinase
      inhibitor aprotinin and the specific elastase-inhibitor eglin C failed to inhibit
      complement activation, whereas leukocyte depletion could partially abolish the
      increase of the concentration of C4a, but had no effect on C3a concentrations.
      These observations support the notion that cleavage of C4 during storage of whole
      blood is partially leukocyte dependent, whereas the activation of C3 is possibly
      caused by the activation of the alternate pathway of the complement system by
      contact of plasma with plastic surfaces.

PMID- 1375122
TI  - Expression of CD7 antigen precludes t(8;21)(q22;q22) chromosome aberration in
      acute myeloblastic leukemia.

PMID- 1375123
TI  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony
      stimulating factor (G-CSF): receptor biology, signal transduction, and neutrophil
      activation.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony
      stimulating factor (G-CSF) are two of the growing number of recognized cytokines
      involved in the regulation of hematopoiesis. The purification of these factors
      and the subsequent cloning of the cDNAs which encode these proteins have led to
      their widespread clinical use in the setting of therapy or disease-induced
      myelosuppression. Although originally purified on the basis of their colony
      stimulating properties, GM-CSF and G-CSF may also play important roles in the
      regulation of effector cell function. The mechanisms underlying progenitor cell
      proliferation and effector cell stimulation remain poorly understood. However,
      the characterization of the GM-CSF and G-CSF receptors and recent work in signal
      transduction are helping to elucidate these mechanisms. This paper will review
      the biology of the GM-CSF and G-CSF receptors, the mechanisms of post-receptor
      signal transduction, and the resultant effects on neutrophil function. In
      addition, the current and potential clinical uses of these factors will be
      examined in light of their ability to activate and perhaps enhance the function
      of neutrophils.

PMID- 1375124
TI  - Gene regulation.

PMID- 1375125
TI  - Plasma exudation in rhinitis.

PMID- 1375126
TI  - Diagnostic value of skin and laboratory tests in cow's milk allergy/intolerance.
AB  - The applicability of a panel of five skin and laboratory tests in the diagnosis
      of cow's milk allergy/intolerance (CMAI) was investigated. The tests used were
      prick and patch tests, RAST, basophil histamine release test (BHRT) and
      lymphocyte proliferation test (LPT). Twenty-two atopic children who had
      experienced either immediate or delayed cutaneous symptoms upon challenge with
      cow's milk (CM), and 12 non-milk-allergic controls with atopic dermatitis (AD)
      were included in the study. RAST, prick test, BHRT and LPT to CM and patch test
      to alpha-casein were positive in the CMAI group and non-milk-allergic atopic
      controls as follows: 59% and 33%, 57% and 0%, 55% and 17%, 77% and 17%, 33% and
      0%. RAST, prick test and BHRT were more often positive in children exhibiting
      immediate reactions, and patch test and LPT more often positive in those having
      delayed reactions to CM. The panel of five tests detected 21/22 children with
      CMAI and gave false-positive results in 5/12 of non-milk allergic controls. The
      sensitivity and specificity of the panel in the diagnosis of CMAI were 95% and
      58%, respectively.

PMID- 1375127
TI  - Specificity mapping of patients IgE response towards the tree pollen major
      allergens Aln g I, Bet v I and Cor a I.
AB  - The specificity pattern of IgE from non-treated tree pollen allergic patients (n
      = 38) were evaluated by solid phase absorption of serum samples followed by CRIE
      on alder, birch and hazel CIE precipitation profiles. The majority of the serum
      samples seemed to contain IgE antibodies with the following characteristics:
      specific towards Bet v I alone and common between Aln g I, Bet v I and/or Cor a
      I, 'II'. The IgE specificity profiles observed for 95% of the sera tested are
      compatible with birch pollen allergens being the only sensitizing allergens,
      indicating that the patients react to allergens from other tree pollens of the
      Fagales order due to IgE cross-reaction with the major allergens of birch and
      alder and/or hazel pollens.

PMID- 1375128
TI  - Inhibition profiles of sodium cromoglycate and nedocromil sodium on mediator
      release from mast cells of human skin, lung, tonsil, adenoid and intestine.
AB  - We have studied an aspect of the functional heterogeneity of human mast cells,
      namely responsiveness to the inhibitory effects of sodium cromoglycate and
      nedocromil sodium. The effects of these drugs were examined on the release of
      histamine and PGD2 from mast cells of human skin, lung, tonsils, adenoids and
      intestine. A high concentration, 1000 microM, of sodium cromoglycate was required
      to significantly inhibit histamine release from lung and tonsillar mast cells.
      Nedocromil sodium, 1000 microM, was more effective than sodium cromoglycate
      against histamine release from lung, tonsillar and adenoidal cells. Both
      compounds showed tachyphylaxis in lung and tonsillar mast cells but not in
      adenoidal and intestinal mast cells. In contrast, in intestinal mast cells, the
      effect of nedocromil sodium was weaker and more variable than sodium
      cromoglycate. Skin mast cells differed from mast cells of the other anatomical
      sites in being unresponsive to sodium cromoglycate and nedocromil sodium. Our
      results confirm that high concentrations of sodium cromoglycate and nedocromil
      sodium are required to achieve even modest inhibition of mediator release from
      human mast cells under in vitro conditions. Notwithstanding this, the results
      also indicate that differences exist among skin, lung, tonsillar, adenoidal and
      intestinal mast cells with respect to their sensitivity to sodium cromoglycate
      and nedocromil sodium, thus extending our knowledge of functional heterogeneity
      within the human mast cell populations.

PMID- 1375129
TI  - Unpacking the incoming influenza virus.

PMID- 1375130
TI  - Signal peptides open protein-conducting channels in E. coli.
AB  - Plasma membrane vesicles and protoplasts of Escherichia coli were fused to planar
      lipid bilayers and studied with electrophysiological techniques. Large
      transmembrane aqueous channels were opened when 0.2 nM LamB signal peptide was
      added to the cytoplasmic side of the membrane. These aqueous pores are similar in
      conductance to those previously observed in mammalian endoplasmic reticulum when
      puromycin is used to release and thus unplug nascent translocating chains. Signal
      sequences have been previously shown to be necessary and sufficient for targeting
      proteins to cellular membranes. These results demonstrate that signal peptides
      are sufficient for opening the protein-conducting channels. We suggest that they
      are the physiological ligands that open protein-conducting channels at the
      initiation of protein translocation across prokaryotic plasma membrane and
      mammalian endoplasmic reticulum.

PMID- 1375131
TI  - Signaling from LFA-1 contributes signal transduction through CD2 alternative
      pathway in T cell activation.
AB  - LFA-1, a member of the integrin family of molecules, is involved in mediating
      cellular adhesion in all phases of the immune response, playing a role in the
      interaction of helper T cells as well as in killing of target cells by both
      cytotoxic T cells and natural killer cells. We have developed a monoclonal
      antibody, anti-HVS6B6, which recognizes a functionally unique epitope of the LFA
      1 molecule. Although this mAb itself was not mitogenic against T cells, it
      induced a strong proliferative response when added to T cells with submitogenic
      concentrations of anti-CD2 (anti-T11(2) and anti-T11(3)) mAbs. In contrast, other
      anti-LFA-1 mAbs (CD11a and CD18) suppressed this anti-CD2 mAb-induced T cell
      proliferation. Kinetic studies showed that anti-HVS6B6 acts on an early event in
      CD2-mediated T cell activation. Although T11(3)-epitope expression induced by
      anti-T11(2) mAb was not affected by treatment of cells with anti-HVS6B6, both
      Ca2+ influx and phosphatidylinositol turnover induced by anti-CD2 mAbs were
      markedly enhanced by the pretreatment of T cells with anti-HVS6B6 mAb. These
      results indicate that the LFA-1 mediating signal contributes to a very early
      phase of signal transduction during CD2-mediated T cell activation.

PMID- 1375132
TI  - The substitution of cysteine 17 of recombinant human G-CSF with alanine greatly
      enhanced its stability.
AB  - Human recombinant granulocyte-colony stimulating factor (rhG-CSF) has one free
      cysteine at position 17 and has two disulfide bridges (Cys36-Cys42 and Cys64
      Cys74). The Cys17 of rhG-CSF was substituted with Gly, Ala, Ser, Ile, Tyr, Arg,
      and Pro, or deleted using site-directed mutagenesis in order to improve its
      thermostability. With the exception of Pro17-rhG-CSF, all mutant proteins
      retained biological activity which promotes the growth of mouse bone marrow cells
      in vitro. Among these mutant proteins, Ala17-rhG-CSF had more than 5 times higher
      stability than rhG-CSF. But Ser17-rhG-CSF had almost same stability as rhG-CSF
      and other mutant proteins had only lower stability.

PMID- 1375133
TI  - Studies on the mechanism of the synergistic interaction between 2'-deoxy-5
      azacytidine and cisplatin.
AB  - 2'-Deoxy-5-azacytidine (5-aza-CdR) and cisplatin interact to produce synergistic
      cytotoxicity against many human tumor cell lines. Preliminary experiments
      designed to explore the mechanism of this synergy suggested a poor correlation
      between synergy and the degree of genomic hypomethylation measured following
      exposure to 5-aza-CdR. Subsequent studies using plasmid DNA suggested that rather
      than DNA hypomethylation, incorporation of 5-aza-CdR into DNA mediated increased
      cisplatin binding to DNA and could therefore be essential to the synergistic
      interaction between these two agents. In this series of experiments, we evaluated
      the degree of synergy with cisplatin produced against two human melanoma cell
      lines by two additional antimetabolites that were chosen on the basis of their
      biochemical properties. In addition, we investigated the synergy between 5-aza
      CdR and cisplatin in parental and 5-aza-CdR-resistant murine cell lines, which
      differed in their sensitivity to 5-aza-CdR and DNA methylation status but
      incorporated similar amounts of 5-aza-CdR into DNA when exposed to this
      antimetabolite. In the studies testing additional antimetabolites, cytosine
      arabinoside, which is incorporated into DNA but does not hypomethylate it,
      produced synergy with cisplatin that was similar or superior to that obtained
      using 5-aza-CdR. With 3-deaza-adenosine, which is not incorporated into DNA but
      produces DNA hypomethylation through inhibition of S-adenosylhomocysteine
      hydrolase, a primarily antagonistic interaction was observed in the two cell
      lines studied. In the 5-aza-CdR-sensitive and -resistant cell lines, a very
      similar synergistic interaction was documented for 5-aza-CdR and cisplatin
      despite the significant difference observed in DNA methylation levels. Taken as a
      whole, these data suggest that DNA hypomethylation was not critical to the
      synergistic cytotoxicity produced by 5-aza-CdR and cisplatin. This finding
      suggests additional strategies that could further modulate this interaction.

PMID- 1375134
TI  - Potent inhibitors for the deamination of cytosine arabinoside and 5-aza-2'
      deoxycytidine by human cytidine deaminase.
AB  - Deamination of the nucleoside analogues ARA-C and 5-AZA-CdR by CR deaminase
      results in a loss of antileukemic activity. To prevent the inactivation of these
      analogues, inhibitors of CR deaminase may prove to be useful agents. In the
      present study we investigated the effects of the deaminase inhibitors Zebularine,
      5-F-Zebularine, and diazepinone riboside on the deamination of CR, ARA-C, and 5
      AZA-CdR using highly purified human CR deaminase (EC 3.5.4.5). These inhibitors
      produced a competitive type of inhibition with each substrate, the potency of
      which followed the patterns diazepinone riboside greater than 5-F-Zebularine and
      THU greater than Zebularine. 5-AZA-CdR was more sensitive than ARA-C to the
      inhibition produced by these deaminase inhibitors. The inhibition constants for
      diazepinone riboside lay in the range of 5-15 nM, suggesting that this inhibitor
      could be an excellent candidate for use in combination chemotherapy with either
      ARA-C or 5-AZA-CdR in patients with leukemia.

PMID- 1375135
TI  - Radiotherapy in the treatment of middle ear and mastoid carcinoma.
AB  - The treatment of temporal bone carcinoma is a widely discussed topic with marked
      variation in published results. Most conclude that a combination of radical
      surgery and radiotherapy is the optimum treatment. The present study reviews the
      results of radiotherapy used as the main primary treatment for this condition.
      Five-year survival in 56 patients was 32% for radical and palliative therapy,
      with an excellent response in 'early' cases. It is concluded that improvement in
      survival could be attained by defining those groups which would benefit from a
      combination of treatment methods.

PMID- 1375136
TI  - Factors affecting ciliary function in vitro: a preliminary study.
AB  - Nasal ciliary function forms an important defence mechanism within the upper
      respiratory tract which has largely been ignored in recent years. The effects of
      various drugs used extensively in the treatment of diseases of the nose have not
      been fully established. Furthermore, the physiological control of ciliary
      activity is unclear. The aim of this study was therefore to investigate the
      effects of drugs on ciliary beat frequency in vitro using a photometric
      technique. A dose-dependent response to alpha and beta receptor drugs was found,
      cocaine hydrochloride achieved ciliostasis even at 40-fold dilution, and
      potassium ions, except at the limits of tolerance for excitable tissue, did not
      affect ciliary function. In conclusion, we suggest that alpha and beta receptors
      may be present on ciliated epithelium and be involved in the control of ciliary
      function in vivo. Ion fluxes across the ciliary cell membrane may also be
      important in ciliary activity akin to nervous tissue.

PMID- 1375137
TI  - Zymosan induced 45Ca uptake by retinal pigment epithelial cells.
AB  - 45Ca uptake was studied in isolated frog retinal pigment epithelial cells in
      response to the phagocytic stimuli, zymosan. 45Ca uptake was strongly stimulated
      immediately in the presence of zymosan particles. Calcium uptake was proportional
      to the zymosan concentrations. After 60 min in the presence of zymosan acid
      phosphatase and beta-glucuronidase activities showed a 25% and 50% increase,
      respectively. Rod outer segments induced a similar increase of these enzyme
      activities. The zymosan-induced lysosomal enzyme activities was inhibited by
      cytochalasin B and ruthenium red. The ionophore A23187 produced a remarkable
      increase in 45Ca uptake but did not affect the lysosomal enzyme activities. These
      results suggest that in vitro RPE cells are able to respond to zymosan as
      phagocytosable stimuli and that calcium mediate that response.

PMID- 1375139
TI  - [The use of alpha-receptor blockers in urological diseases].

PMID- 1375138
TI  - Inapparent ocular infection by Chlamydia trachomatis in experimental and human
      trachoma.
AB  - There is substantial indirect evidence which suggests that Chlamydia trachomatis
      can generate inapparent, persistent infections in human. To confirm this
      directly, we examined ocular chlamydial infection in both the cynomolgus monkey
      model of trachoma and in patient samples from a trachoma-endemic area. In
      monkeys, ocular infection was studied over time using direct immunofluorescence
      cytology (DFA) and a molecular hybridization screening system which targets
      chlamydial ribosomal RNA. In eleven animals infected once with B serovar, DFA and
      probe screening of parallel conjunctival swabs gave congruent results through day
      42 post-infection. Thereafter, DFA showed clearing of chlamydia and was negative
      by day 70, as in previous studies. In contrast, hybridization analysis indicated
      a continuing presence of chlamydial RNA in all samples from all animals through
      the end of the experiment at day 84 post-infection. Similarly, analysis of swabs
      from trachoma patients showed that a number of DFA-negative samples gave clear
      positive signal for chlamydial RNA. Taken together these data indicate that
      ocular chlamydial infection persists for longer periods than previously thought,
      judging solely on the basis of DFA, and they support the idea that inapparent
      ocular chlamydial infection occurs in vivo.

PMID- 1375140
TI  - Insulin-like growth factor-1 and insulin-like growth factor binding protein-1 in
      early human pregnancy.
AB  - Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding
      protein-1 (IGFBP-1) were measured in amniotic fluid, extraembryonic coelomic
      fluid and maternal serum from 23 women with apparently normal first trimester
      pregnancies prior to termination. The levels of IGF-1 and IGFBP-1 were
      significantly higher in coelomic fluid than amniotic fluid (IGF-1, P = 0.006;
      IGFBP-1, P = 0.0008 (paired t-test)). The levels of IGFBP-1 were lower in
      amniotic fluid than in maternal serum (P = 0.017), a finding in sharp contrast to
      the situation in the second and third trimesters of pregnancy. There was a
      significant relation between levels of IGF-1 and IGFBP-1 in amniotic fluid (r =
      0.43; P = 0.04) and in coelomic fluid (r = 0.81; P less than 0.001) but not in
      maternal serum. The finding that both the absolute levels of IGFBP-1 and the
      ratio to IGF-1 were low in amniotic fluid implies that there is a very high level
      of unbound, biologically active IGF-1 in this compartment in the first trimester.
      Thus, the regulatory role of IGFBP-1 may change as pregnancy advances.

PMID- 1375141
TI  - Protective effects of Ca2+, Mg2+, Cu2+, and Ni2+ on mercury and methylmercury
      toxicity to a cyanobacterium.
AB  - Toxicological investigations of the impact of inorganic mercury (Hg2+) and
      methylmercury (CH3Hg+) in terms of growth, NH4+ uptake, in vivo glutamine
      synthetase (transferase) activity, and regulation of toxicity by Ca2+, Mg2+, Cu2+
      and Ni2+ in the diazotrophic cyanobacterium Nostoc calcicola Breb. have been
      completed. Photoautotrophic growth of the cyanobacterium was extremely sensitive
      to both mercury compounds, CH3Hg+ being 2.5 times more toxic than Hg2+. Although
      NH4+ uptake was 6 times more sensitive than in vivo GS activity against the two
      mercurials, both processes had a greater susceptibility toward CH3Hg+. On the
      basis of Km and Vmax, it is suggested that both mercury species inhibit such
      metabolic events noncompetitively. Ca2+, Mg2+, Cu2+, and Ni2+ did not change the
      nature of inhibition and effectively antagonized the Hg2+ and CH3Hg+ toxicities
      in the sequence Ca2+ greater than Mg2+ much greater than Cu2+ greater than Ni2+.

PMID- 1375142
TI  - Milt characteristics, reproductive performance, and larval survival and
      development of white sucker exposed to bleached kraft mill effluent.
AB  - White sucker from a Lake Superior bay which receives bleached kraft mill effluent
      (BKME) show increased hepatic mixed-function oxygenase (MFO) activity, reduced
      plasma sex steroid levels, decreased egg and gonad size, a decrease in the
      occurrence of secondary sexual characteristics, and an increased age to
      maturation. This study evaluated the reproductive performance of that white
      sucker population relative to a similar reference population. Spawning male white
      sucker from the BKME site had reduced spermatozoan motility but no significant
      differences in milt volume, spermatocrit levels, or seminal plasma constituents.
      BKME male and female fish had equal or greater fertilization potential compared
      to both male and female fish at the reference site. There was no difference
      either in the hatchability of the eggs or in larval size at hatch. BKME larvae
      did show reduced growth rates by 24 days posthatch but showed equal rates of yolk
      utilization. No difference in larval MFO activity was detected between sites at
      21 days posthatch, indicating no parental transfer of induction to the progeny.

PMID- 1375143
TI  - Joint action between binary mixtures of chlordimeform and insecticides.
AB  - Chlordimeform (CDF) was tested for its ability to act jointly with an
      organophosphorus insecticide (parathion) and a series of carbamate insecticides.
      Three arthropod species were used as test subjects: the two-spotted spider mite,
      Tetranychus urticae; the German cockroach, Blatella germanica; and the flour
      beetle, Tenebrio castaneum. However, CDF antagonized the toxicity of parathion
      toward B. germanica while it acted in a greater than additive fashion toward T.
      castaneum. No combination of CDF and insecticide tested acted jointly toward T.
      urticae. Species-specific differences in sensitivity, absorption, metabolism, and
      mode of delivery account for the varying results. Metabolic studies of pairs of
      compounds using two radiolabeled carbamates showed that CDF altered the metabolic
      detoxification of both carbaryl and aldicarb. The results suggest that CDF may
      inhibit MFOs as its mode of action.

PMID- 1375144
TI  - Coplanar PCBs in fish and mussels from marine and estuarine waters of New York
      State.
AB  - Thirty samples of striped bass from marine and estuarine waters of New York
      State, six samples of mussels from Long Island Sound, and one composite sample of
      freshwater mussels from Troy were analyzed by a recently developed method which
      combines sulfuric acid cleanup, carbon chromatography, and high-resolution gas
      chromatography for the determination of non-ortho- and mono-ortho-substituted
      polychlorinated biphenyls (PCBs), which are biologically active congeners of PCBs
      and approximate isostereomers of 2,3,7,8-tetrachlorodibenzo-P-dioxin of (2,3,7,8
      TCDD). Non-ortho coplanar PCBs ranged from 0.2 to 37.1 ppb in fish. The highest
      concentrations of 37.1 ng/g of 3,3',4,4'-tetrachlorobiphenyl (77) and 7.5 ng/g of
      3,3',4,4',5-pentachlorobiphenyl (126) were detected in a fish caught near
      Troy/Albany, New York. Mono-ortho-substituted PCBs ranged from 0.4 to 790 ppb in
      fish, with the major components identified as 2,3',4,4',5-penta-(118) and
      2,3,3',4,4'-pentachlorobiphenyls (105). When concentrations were converted to
      2,3,7,8-TCDD picogram equivalents, 99% of the equivalents were derived from three
      congeners (77, 105, and 126), 3,3',4,4',5-pentachlorobiphenyl (126) accounting
      for approximately 80% of the activity. At Troy pg/g TCDD equivalents derived from
      PCB were approximately 3000, whereas the actual 2,3,7,8-TCDD concentration was
      only 20 pg/g; hence, accurate coplanar PCB measurement is important.

PMID- 1375145
TI  - Impact of malathion and gamma-BHC on lipid metabolism in the freshwater female
      catfish, Heteropneustes fossilis.
AB  - Female Heteropneustes fossilis were exposed to sublethal concentrations of
      malathion (5 and 20 microliters liter-1) and gamma-BHC (4 and 16 micrograms liter
      1) for 4 weeks during different phases of their annual reproductive cycle. The
      impact of these pesticides on free fatty acids (FFA), monoglycerides (MG),
      diglycerides (DG), triglycerides (TG), phospholipids (PL), free cholesterol (CF),
      and esterified cholesterol (CE) in the liver, plasma, and ovary was assessed.
      During the preparatory phase both the pesticides reduced the levels of all the
      hepatic and ovarian lipids with elevated hepatic CE. During the prespawning phase
      these pesticides decreased all the lipids in the liver, plasma, and ovary with
      the elevation of hepatic FFA and CE. During the spawning phase a reduction of
      hepatic MG and CF with a decreased level of plasma and ovarian levels of FFA and
      PL was recorded, whereas ovarian levels of TG and CE were elevated in response to
      both the pesticides. During postspawning and resting phases all the hepatic
      lipids were reduced with the elevation of CE in response to the exposure. These
      pesticides also restricted their mobilization to the ovary. Cholesterol
      biosynthesis seemed unaffected but the hydrolysis of CE to CF was adversely
      affected during preparatory and prespawning phases which is a period of sex
      steroid hormone biosynthesis.

PMID- 1375146
TI  - Accumulation of lead and effects on total lipids and lipid derivatives in the
      freshwater fish Anabas testudineus (Bloch).
AB  - Exposure of a freshwater fish to several sublethal concentrations (1.25, 2.50,
      5.00, 10.00, and 20.00 mg/liter) of lead for a period of 30 days showed
      significant accumulation of lead in the blood and tissues. Lead bioaccumulated in
      the study showed organ-specific distribution, with high levels in the blood
      followed by the kidney, gill, liver, and brain and comparatively lesser amounts
      in the ovary and muscle tissues. The lead accumulation in tissues was found to
      increase with lead in water up to a concentration of 5 mg/liter, and at
      concentrations of 10 and 20 mg/liter the lead accumulation in the tissues,
      although indicating an increase, was not proportional to the concentration in
      water. Exposure of the freshwater fish Anabas testudineus to a sublethal (5 ppm)
      concentration of lead nitrate for a period of 30 days during the preparatory
      phase of its annual reproductive cycle reduced the total lipids, phospholipids,
      and cholesterol levels in the liver and ovary tissues while the free fatty acid
      levels were increased and lipase activity was elevated. All the parameters in the
      blood were found to increase. These results suggest that lead nitrate affects the
      lipid metabolism of the fish and this may reduce the fecundity of the fish since
      lipids are known to play an important role in teleost reproduction as an energy
      source and a precursor of steroids.

PMID- 1375147
TI  - The effect of pesticides on carp (Cyprinus carpio L). Acetylcholinesterase and
      its biochemical characterization.
AB  - The activity and molecular forms of acetylcholinesterase (AChE) were
      characterized in tissues of the carp (Cyprinus carpio). Tissue AChE activity was
      determined in response to specific inhibitors (ethopropazine, BW 284 C51) or
      pesticides (CuSO4, paraquat (PQ), methidathion (MD)). The highest AChE activity
      was found in the serum (878 +/- 100 U/liter), followed by the brain (113 +/- 12
      U/liter), heart (89 +/- 6 U/liter), and trunk muscle (35 +/- 5 U/liter).
      Experiments with specific choline esterase inhibitors revealed a very low amount
      of pseudocholinesterase in all tissues studied. The ratio of the membrane-bound
      to the cytoplasmic-free AChE molecular forms was increased in the order of brain,
      trunk muscle, and heart. In sera of fish treated with MD (2 ppm) there was an 80%
      inhibition of AChE lasting for 2 weeks. Treatment with CuSO4 or PQ (both 5 ppm)
      led to a 50% decrease in the serum AChE activity followed by a transient increase
      over the control level. After 2 weeks of chronic treatment, AChE activity in fish
      exposed to CuSO4 returned to the control level, whereas in fish treated with PQ
      an elevated level (130% when compared to the control level) of enzyme activity
      was found. Our present experimental data indicate that pesticides occurring in
      natural waters not only inhibit AChE activity in fish but may influence the
      resynthesis of the enzyme as well.

PMID- 1375149
TI  - Bioconcentration kinetics of the organophosphorus insecticide chlorpyrifos in
      guppies (Poecilia reticulata).
AB  - The bioconcentration kinetics of chlorpyrifos (O,O-diethyl O-3,5,6-trichloro-2
      pyridyl phosphorothioate) in guppies (Poecilia reticulata) were investigated. A
      static exposure was used to study the uptake of the compound. The amount absorbed
      was calculated from the difference in disappearance rates from the water phase in
      aquaria with and without fish. The uptake rate was found to be first-order with
      respect to the exposure concentration, and amounts to ca. 38 ml g-1 (fish) hr-1.
      The elimination rate was studied in separate experiments. Guppies were first
      given the opportunity to accumulate chlorpyrifos and, following transfer to clean
      water, the clearance of the compound was measured by determining the residual
      chlorpyrifos in the fish. It was found that the elimination rate was first-order
      with respect to the concentration in fish, but depended slightly on the length of
      the preexposure period. The half-life of tissue chlorpyrifos varied from 31 to 38
      hr. Release of unchanged chlorpyrifos turned out to be negligible relative to the
      amount eliminated. This indicates that metabolic breakdown is the only pathway
      for elimination. From the kinetic rate parameters, a bioconcentration factor was
      calculated of about 1700. This value is very similar to that measured directly
      after an 8-day semistatic exposure. A two-compartment model is proposed to
      describe the kinetics of the bioconcentration process. The conditions limiting
      the applicability of the indirect method for measuring the toxicokinetics of
      chlorpyrifos are discussed.

PMID- 1375148
TI  - Integrated assessment of contaminated sediments in the lower Fox River and Green
      Bay, Wisconsin.
AB  - Samples of sediment and biota were collected from sites in the lower Fox River
      and southern Green Bay to determine existing or potential impacts of sediment
      associated contaminants on different ecosystem components of this Great Lakes
      area of concern. Evaluation of benthos revealed a relatively depauperate
      community, particularly at the lower Fox River sites. Sediment pore water and
      bulk sediments from several lower Fox River sites were toxic to a number of test
      species including Pimephales promelas, Ceriodaphnia dubia, Hexagenia limbata,
      Selenastrum capricornutum, and Photobacterium phosphorum. An important component
      of the observed toxicity appeared to be due to ammonia. Evaluation of three
      bullhead (Ictalurus) species from the lower Fox River revealed an absence of
      preneoplastic or neoplastic liver lesions, and the Salmonella typhimurium
      bioassay indicated relatively little mutagenicity in sediment extracts. Apparent
      adverse reproductive effects were noted in two species of birds nesting along the
      lower Fox River and on a confined disposal facility for sediments near the mouth
      of the river, and there were measurable concentrations of potentially toxic
      2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans
      (PCDFs), and planar polychlorinated biphenyls (PCBs) both in the birds and in
      sediments from several of the study sites. Based on toxic equivalency factors and
      the results of an in vitro bioassay with H4IIE rat hepatoma cells, it appeared
      that the majority of potential toxicity of the PCB/PCDF/PCDD mixture in biota
      from the lower Fox River/Green Bay system was due to the planar PCBs. The results
      of these studies are discussed in terms of an integrated assessment focused on
      providing data for remedial action planning.

PMID- 1375150
TI  - Toxicity of lindane to freshwater insect larvae in compartments of an
      experimental pond.
AB  - The acute and chronic toxicities of lindane to larvae of the freshwater insects
      Chironomus riparius Meigen, Chaoborus flavicans (Meigen), and Sigara striata (L.)
      were investigated in mesocosm compartments of an experimental pond. The following
      median lethal concentrations (LC50s) were determined: 240-hr LC50 of 2.0
      micrograms lindane liter-1 for second instar C. riparius, 72-hr LC50 of 6.5
      micrograms lindane liter-1 for fourth instar C. riparius, and 96-hr LC50s of 4.0
      and 3.9 micrograms lindane liter-1 for fourth instar C. flavicans and fourth or
      fifth instar S. striata, respectively. Lindane significantly reduced the growth
      over 10 days of second instar C. riparius compared to that of the control at the
      treatment concentrations where larvae survived (1.0, 2.5, and 7.0 micrograms
      lindane liter-1). A significant increase in the median emergence time in
      comparison to that of the control was observed for C. riparius exposed to 0.8 and
      2.0 micrograms lindane liter-1, with higher concentrations causing 100%
      mortality. The findings compare well with previously reported laboratory data on
      the toxicity of lindane to insects and support the methodology and results of a
      laboratory growth test for C. riparius.

PMID- 1375152
TI  - Endoscopic papillotomy in biliary tract pain and fluctuating cholestasis with
      common bile duct dilatation and small gallbladder stones.
AB  - In patients suspected of having functional disorders of the papilla it is often
      difficult to establish the indications whether or not to perform endoscopic
      papillotomy (EP). We report on thirty-two consecutive patients referred for
      endoscopic retrograde cholangiopancreatography who all had longstanding biliary
      tract pain and episodes of liver enzyme elevation indicating cholestasis. Further
      features were: 1) a dilated common bile duct (CBD) after cholecystectomy (n = 11)
      or 2) a dilated CBD without or with larger (greater than cystic duct diameter)
      gallbladder stones (n = 6) or 3) multiple small gallbladder stones, with a normal
      or dilated CBD, in patients with signs of acute gallstone pancreatitis or in whom
      elective cholecystectomy was not indicated (n = 15). No CBD stones, organic
      obstruction or other disorders were found in these patients. Without further
      diagnostic procedures, EP was routinely performed. The laboratory (up to 3
      months) and clinical findings (2 to 4 years follow up) showed improvement in all
      patients undergoing EP. We conclude that immediate EP appears justified in these
      selected patients.

PMID- 1375151
TI  - Effects of hepatotoxicants on the induction of microsomal monooxygenase activity
      in sunfish liver by beta-naphthoflavone and benzo[a]pyrene.
AB  - Effects of chemically induced hepatic injury on biotransformation enzymes in fish
      were studied. Sunfish hybrids (Lepomis macrochirus x L. cyanellus) were dosed per
      os with allyl formate (ALF) and carbon tetrachloride (CCl4), and the induction of
      liver EROD (7-ethoxyresorufin O-deethylase) activity was subsequently challenged
      by injections of beta-naphthoflavone (BNF) and benzo[a]pyrene (B[a]P).
      Hepatotoxicity of chemical treatments was assessed using blood enzymes (ASAT,
      ALAT, and LDH) along with other biochemical variables. Both hepatotoxicants
      partially abolished the induction of EROD (maximally by 76-89%), and the decrease
      in induction was dose related. The cytosolic activity of glutathione S
      transferase (GST) in the liver decreased in parallel with the decrease in EROD
      induction. Fish receiving high doses of ALF exhibited significantly less
      microsomal and blood plasma proteins and, occasionally, were jaundiced. These
      symptoms, however, were less sensitive indicators of hepatotoxicity than
      alterations in liver EROD and GST. Both ALF and CCl4 increased the activities of
      hepatic enzymes in the blood plasma, indicating cytotoxicity. In addition B[a]P,
      unlike BNF, also increased plasma activities of LDH and ALAT at a dose inducing
      liver EROD, implying simultaneous hepatotoxicity at high sublethal levels of this
      xenobiotic. These data suggest that hepatotoxic chemicals absorbed by fish may
      act antagonistically by decreasing the degree of induction of the cytochrome P450
      system relative to the inherent capacity of inducing xenobiotic chemicals present
      in the environment. Therefore, when assessing the toxicological status of water
      using fish health biomarkers, it is advisable to measure a concert of metabolic
      and biochemical variables instead of any single biomarker.

PMID- 1375153
TI  - An explanation of the achromatic bands produced by peroxidase isozymes in
      polyacrylamide electrophoresis gels stained for malate dehydrogenase.
AB  - When plant tissue extracts are electrophoresed on polyacrylamide gels and the
      gels are stained for malate dehydrogenase by the standard NAD-dependent
      dehydrogenase reaction, terminating in the formation of reduced Nitroblue
      Tetrazolium (NBT), achromatic bands, in addition to the expected chromatic bands,
      are observed. The achromatic bands are seen when the staining conditions favor a
      generalized background staining of the gel and have been shown, in a previous
      study, to be caused by peroxidase isozymes [1]. The present study examined the
      mechanism by which peroxidase produced the achromatic bands using horseradish
      peroxidase (HRP). The generalized background staining resulted from the phenazine
      methosulfate (PMS)-mediated reduction of NBT. This reduction was enhanced by H2O2
      and suppressed by HRP. Peroxidase apparently catalyzes the peroxidative oxidation
      of reduced PMS, which suppresses the generalized reduction of NBT in gel regions
      containing peroxidase isozymes producing the achromatic bands. In contrast,
      however, HRP also appears to catalyze the peroxidative oxidation of reduced NAD,
      but this reaction increases the reduction of NBT. The results are discussed in
      the context of the mechanisms proposed by others for the PMS-mediated reduction
      of NBT and for the peroxidase-catalyzed NADH-dependent formation of H2O2. This
      peroxidase-catalyzed reaction has been proposed for the plant peroxidases
      involved in lignification.

PMID- 1375154
TI  - Specific inhibition of Physarum polycephalum DNA-polymerase-alpha-primase by
      poly(L-malate) and related polyanions.
AB  - Poly(L-malate) is an unusual polyanion found in nuclei of plasmodia of Physarum
      polycephalum. We have investigated, by enzymatic and fluorimetric methods,
      whether poly(L-malate) and structurally related polyanions can interact with DNA
      polymerase-alpha-primase complex and with histones of P. polycephalum. Poly(L
      malate) is found to inhibit the activities of the DNA-polymerase-alpha-primase
      complex and to bind to histones. The mode of inhibition is competitive with
      regard to DNA in elongation and noncompetitive in the priming of DNA synthesis.
      Spermidine, spermine, and histones from P. polycephalum and from calf thymus bind
      to poly(L-malate) and antagonize the inhibition. The polyanions poly(vinyl
      sulfate), poly(acrylate), poly(L-malate), poly(D,L-malate), poly(L-aspartate),
      poly(L-glutamate) have been examined for their potency to inhibit the DNA
      polymerase. The degree of inhibition is found to depend on the distance between
      neighboring charges, given by the number of atoms (N) interspaced between them.
      Poly(L-malate) (N = 5) and poly(D,L-malate) (N = 5) are the most efficient
      inhibitors, followed by poly(L-aspartate) (N = 6), poly(acrylate) (N = 3), poly(L
      glutamate) (N = 8), poly(vinyl sulfate) (N = 3). It is proposed that poly(L
      malate) interacts with DNA-polymerase-alpha-primase of P. polycephalum. According
      to its physical and biochemical properties, poly(L-malate) may alternatively
      function as a molecular chaperone in nucleosome assembly in the S phase and as
      both an inhibitor and a stock-piling agent of DNA-polymerase-alpha-primase in the
      G2 phase and M phase of the plasmodial cell cycle.

PMID- 1375155
TI  - Dynamics of the exposure of epitopes on OmpF, an outer membrane protein of
      Escherichia coli.
AB  - The OmpF protein is the major outer membrane trimeric porin of Escherichia coli
      B. The exposure of several cell-surface-exposed epitopes, that are recognized by
      various monoclonal antibodies directed against the protein, is investigated.
      Kinetic analyses show that two epitopes (E18 and E19) appear early during the in
      vivo assembly on the folded monomer, just after the removal of the signal
      peptide, and are conserved in the native trimer. The trimerization that
      immediately follows or occurs in conjunction with the folding of monomers exposes
      another antigenic site (E21) at the surface of metastable forms. The binding of
      nascent lipopolysaccharide promotes the conversion of the heat-modifiable
      intermediate to a stable trimer and ensures the exposure of E20, E1, E3, E4 and
      E7. Late epitopes, E1, E3, E4 and E7 are only detected in the outer membrane
      fraction. These results suggest that different steps induce the sequential
      exposure of native antigenic sites. The detection of these epitopes depends on
      conformational changes occurring during the OmpF insertion into the outer
      membrane.

PMID- 1375157
TI  - Treatment of hemorrhagic hypotension with hypertonic/hyperoncotic solutions:
      effects on regional cerebral blood flow and brain surface oxygen tension.
AB  - Hypertonic/hyperoncotic solutions (e.g. HHS: 7.2% NaCl/10% dextran-60) are highly
      effective to normalize cardiovascular function in hemorrhagic shock due to rapid
      mobilization of fluid from the extravascular compartment. Since experiences are
      limited with regard to potential side effects of this treatment on the central
      nervous system, the present studies were carried out under particular
      consideration of the cerebral blood flow and O2 supply. HHS was administered in
      albino rabbits subjected to alpha-chloralose anesthesia and artificial
      ventilation with and without hemorrhagic hypovolemia. Hemorrhagic hypovolemia of
      30 min duration was induced by withdrawal of approximately one third of the
      circulating blood volume resulting in a decrease in arterial blood pressure to 40
      mm Hg. HHS was studied in addition to normovolemic animals. Cardiac output was
      rapidly normalized by infusion of HHS in animals with hypovolemia, while it
      increased intermittently in normovolemic animals. In animals with hemorrhagic
      shock arterial blood pressure recovered by treatment to approximately 70% of
      normal, whereas blood pressure remained unchanged after infusion of HHS in
      normovolemic controls. Cerebral blood flow, which was assessed by H2 clearance at
      the brain surface, had a range of 43.0-50.3 ml/100 g/min under control
      conditions. It remained virtually unchanged during hemorrhagic hypovolemia and
      also after infusion of HHS in normovolemic animals. Treatment of shock by HHS was
      followed 90 or 120 min later by a moderate increase in regional cerebral blood
      flow to 61 ml/100 g/min. Local tissue PO2 at the brain surface was obtained by an
      O2 multiwire electrode in the vicinity of the H2 clearance measurements using a
      weightless suspension system to avoid compression of the brain surface. Infusion
      of HHS in normovolemic animals did not affect the O2 supply of the brain.
      Hemorrhagic hypovolemia which led to a left shift of the cerebral PO2 histogram
      was followed by gradual normalization after fluid resuscitation. The current
      findings taken together do not indicate adverse side effects of this efficient
      method of fluid resuscitation with regard to the cerebral blood and O2 supply.
      The results make worthwhile further investigations on HHS in the presence of a
      focal brain lesion causing brain edema to find out whether the HHS are useful
      also for the treatment of intracranial hypertension.

PMID- 1375156
TI  - Quantitative expression patterns of multidrug-resistance P-glycoprotein (MDR1)
      and differentially spliced cystic-fibrosis transmembrane-conductance regulator
      mRNA transcripts in human epithelia.
AB  - P-glycoprotein (MDR1), that confers multidrug resistance in cancer, and the
      cystic-fibrosis transmembrane-conductance regulator (CFTR), that is causative
      defective in cystic fibrosis, belong to the family of ATP-binding transport
      proteins. The expression of MDR1 and CFTR in human epithelial tissues and the
      cell lines T84 and HT29 was estimated by primer-directed reverse transcription
      (RT) and subsequent monitoring of the kinetics of cDNA product formation during
      the polymerase chain reaction (PCR). MDR1 mRNA was found in high levels, 15-50
      amol mRNA/microgram RNA, in the intestine, kidney, liver and placenta, and in low
      levels, 0.2 amol/microgram RNA, in respiratory epithelium. Large amounts of CFTR
      mRNA were measured in the gastrointestinal tract, whereas the kidney, as the
      phenotypically normal organ, and the lung, as the most severely affected organ in
      cystic fibrosis, both contained low amounts, 3 amol CFTR/microgram RNA. CFTR
      transcript levels of 1-5 amol/microgram RNA were determined in lymphocytes and
      lymphoblast cell lines, suggesting that lymphoblasts are an accessible source for
      the study of the molecular pathogenesis of cystic fibrosis. When transcripts were
      scanned by overlapping RT/PCR analyses, only transcript of expected size was
      detected for MDR1 mRNA, where variable in-frame deletions of either exon 4, 9 or
      12 were observed in CFTR mRNA. The complete loss of single exons was seen at
      proportions of 1-40% in all investigated tissues and cell lines with large donor
      to-donor variation. Exons 9 and 12 of the CFTR gene encode parts of the
      evolutionarily well-conserved first nucleotide-binding fold including the two
      Walker motifs. Alternative splicing may give rise to various CFTR forms of
      different function and localization.

PMID- 1375159
TI  - Purification and characterization of human macrophage-derived granulomonopoietic
      enhancing factor (GM-EF).
AB  - A granulomonopoietic enhancing factor (GM-EF) capable of promoting the effect of
      colony-stimulating factors (CSFs) on myeloid progenitor cells has been purified
      to homogeneity from serum-free medium conditioned by fully mature human
      macrophages. GM-EF was a glycoprotein with an apparent molecular weight of 74 kd
      and an isoelectric point of 5.2-5.3. The purified protein was heat stable (75
      degrees C for 30 min) and was sensitive to treatment with trypsin, papain, and
      bacterial protease but not to neuraminidase. The activity of GM-EF could be
      effectively neutralized by GM-EF-specific antiserum, and no antigenic cross
      reactivity was observed using antisera against interleukin (IL)-1, IL-4, and IL
      6. These results suggest that GM-EF is a unique cytokine that is different
      biochemically and antigenically from other hematopoietic enhancing factors such
      as IL-1, IL-4, and IL-6.

PMID- 1375160
TI  - Differential sensitivity of CD34 epitopes to cleavage by Pasteurella haemolytica
      glycoprotease: implications for purification of CD34-positive progenitor cells.
AB  - Our previous studies have shown that a unique glycoprotease from Pasteurella
      haemolytica specifically cleaves only proteins containing sialylated O-linked
      glycans. The hematopoietic progenitor cell antigen, CD34, which is heavily
      glycosylated with both N- and O-linked glycans, is readily cleaved by this
      protease. In this study, we demonstrate that the epitopes detected by five of the
      seven CD34 monoclonal antibodies are removed by the glycoprotease. The
      differential sensitivity of the CD34 epitopes to cleavage with either
      neuraminidase and/or glycoprotease establishes three classes of epitopes: 1)
      (class I) those identified by MY10, B1.3C5, 12.8, and ICH3 that are
      differentially affected by neuraminidase and removed by the glycoprotease; 2)
      (class II) the epitope detected by QBEND 10 that is removed only by the
      glycoprotease; and 3) (class III) those identified by TUK3 and 115.2 that are not
      removed by either enzyme. Cleavage of the 110-kd CD34 structure by the
      glycoprotease generates a major cell-bound fragment of about 75 kd, identified by
      the class III antibodies. We have also used the enzyme to improve the rapid
      recovery of CD34+ cells selected by immunomagnetic affinity techniques. In a
      preclinical model, we separated CD34+ KG1 cells with high yield (90%-95%) and
      high purity (94%-98%) from sham mixtures containing 50% CD34- cells. We also
      separated CD34+ blast cells from a patient in megakaryoblastic crisis of chronic
      myelogenous leukemia. In this case, the purity and yield were 93% and 94%,
      respectively. Enzyme treatment had no detrimental effect on cell viability, and
      the treated cells showed a normal quantitative expression and distribution of
      CD34 antigen as assessed with class III antibodies. We conclude that the P.
      haemolytica glycoprotease has potential to improve the isolation, from human bone
      marrow, of primitive hematopoietic cells that carry the CD34 antigen.

PMID- 1375158
TI  - Histological and immunohistochemical investigations of hydroxyethyl-starch
      deposits in rat tissues.
AB  - Tissue storage of hydroxyethyl starch (HES), a widely used artificial colloid,
      has been reported. In order to clarify whether storage of HES can be detected in
      tissues by immunohistochemical methods, use was made of a polyclonal rabbit anti
      HES antiserum. Thirteen days after a single intravenous injection of HES rats
      were sacrificed and liver, spleen, lymph node, lung, kidney and skin were
      removed. On paraffin sections in all organs the anti-HES antiserum stained mainly
      cells which could be attributed to the mononuclear phagocyte system, as confirmed
      by the use of the antimacrophage monoclonal antibody ED1. The use of a polyclonal
      anti-HES antiserum may allow analysis of long-term storage and possible side
      effects in various tissues of man.

PMID- 1375161
TI  - Long-term recombinant human granulocyte colony-stimulating factor (rhG-CSF)
      treatment severely depresses murine marrow erythropoiesis without causing an
      anemia.
AB  - We hereby report profound effects of long-term granulocyte colony-stimulating
      factor (G-CSF) administration on murine erythropoiesis. Recombinant human (rh)G
      CSF (150 micrograms/kg body weight/day) was administered over 24 days to female
      C57Bl mice. Marrow erythroid colony-forming units (CFU-E) and erythroblast
      numbers declined to less than 5% of normal, whereas splenic erythropoiesis
      simultaneously increased. Splenic erythropoiesis effectively compensated for the
      loss of marrow erythropoiesis as indicated by the maintenance of a normal
      hematocrit. In the marrow the numbers of spleen colony-forming units (CFU-S) and
      erythroid burst-forming units (BFU-E) declined as well. Simultaneously, however,
      these numbers increased both in the spleen and in the peripheral blood by a
      factor of 20 to 30. These findings suggest a continuous migration of stem cells
      and progenitor cells out of the marrow and an efficient seeding in the spleen,
      directly or indirectly induced by G-CSF. In addition the differentiation and/or
      amplification of BFU-E to CFU-E was impaired in the marrow but not in the spleen.
      The marrow and splenic microenvironment also behaved differently with respect to
      granulopoiesis. G-CSF did not lead to an enhanced granuloid amplification in the
      spleen but exerted its proliferation activity mainly in the marrow. These
      findings imply that prolonged G-CSF treatment might cause erythroid depression in
      animals and humans when spleen erythropoiesis is less efficient than in mice.

PMID- 1375162
TI  - Ex vivo expansion of peripheral blood progenitor cells with recombinant
      cytokines.
AB  - Peripheral blood mononuclear cells were isolated and cultured in the presence of
      Steel factor and/or PIXY321, a GM-CSF/IL-3 fusion protein. We compared the number
      of colony forming cells (CFC) per culture on day zero to the number of CFC after
      liquid culture in the presence of these cytokines. After a four day incubation
      with PIXY321 and Steel factor the number of CFU-GM increased 5.6-fold and the
      number of BFU-E increased 2.2-fold in four separate experiments. The expansion on
      day 8 post incubation was 16.1-fold for myeloid colony formation and 9.7-fold for
      erythroid colony formation. These studies demonstrate the potential to expand CFC
      from peripheral blood with a simple ex vivo culture procedure.

PMID- 1375163
TI  - The medullary relay from neck receptors to somatosensory thalamus in the rat: a
      neuroanatomical study.
AB  - Experiments were performed on rats to determine the location of thalamic
      projecting neurones in the medulla which receive direct contacts from neck
      primary afferents. The medullary terminations of primary afferents from the
      cervical region were identified by silver staining their degenerating terminals,
      diffusely filling their axons with horseradish peroxidase (HRP), or reacting for
      transganglionically transported HRP applied to muscle or cutaneous nerves.
      Neurones projecting to the ventrobasal thalamus were identified in the same
      experimental animals by using retrograde transport of HRP or Fluoro-Gold. En
      passant swellings or terminals of neck primary afferents were found in the
      vicinity of neurones projecting to the thalamus in the dorsolateral part of the
      rostral cuneate nucleus, the ventral aspect of the external cuneate nucleus, and
      the border zone between the two. Terminals of neck afferents and retrogradely
      labelled cells also coincided in nucleus x. Putative synaptic contacts were found
      in the region between the dorsolateral part of the rostral cuneate nucleus and
      ventromedial external cuneate nucleus. Cutaneous afferents from the neck were
      associated with thalamic projecting cells located along the dorsolateral border
      of the rostral cuneate nucleus, and afferents from neck muscles were associated
      with thalamic projecting cells in the caudal third of the external cuneate
      nucleus and in nucleus x.

PMID- 1375164
TI  - Isolation rearing of rats alters release of 5-hydroxytryptamine and dopamine in
      the frontal cortex: an in vivo electrochemical study.
AB  - The effects of rearing hooded Lister rats either in groups of seven or singly on
      5-hydroxytryptamine (5-HT) and dopamine (DA) release in the frontal cortex were
      investigated using in vivo voltammetry together with Nafion coated carbon fibre
      micro-electrodes. The selective detection of basal extracellular levels of 5-HT
      with this technique (Peak B) was confirmed with parallel experiments using
      intracranial microdialysis to measure 5-HT and 5-hydroxyindoleacetic acid (5
      HIAA) levels in vivo. The DA voltammetric signal (Peak A) was observed in vivo
      only following pharmacological or electrical stimulation of DA release. Enhanced
      efflux of cortical DA and 5-HT in response to local application of KCl and that
      of 5-HT following parentelar fenfluramine were selectively detected by the
      association: differential pulse voltammetry (DPV)-Nafion coated microbiosensors,
      supporting the capability of this electrochemical method to selectively monitor
      release of these amine neurotransmitters in vivo and in situ. The locomotor
      behaviour data indicated that isolation rearing resulted in augmented locomotor
      activity in a novel environment. In addition, the in vivo voltammetric results
      showed that following KCl or fenfluramine treatment cortical 5-HT release is
      prolonged while that of DA is increased in rats reared in isolation when compared
      with socially reared rats. This imbalance between extracellular levels of DA and
      5-HT recorded in the frontal cortex of rats exposed to isolated housing
      conditions may contribute to the behavioural differences reported between
      isolation and group reared rats.

PMID- 1375165
TI  - Descending projections of Forel's field H neurones to the brain stem and the
      upper cervical spinal cord in the cat.
AB  - 1. Descending projections from Forel's field H (FFH) to the brain stem and upper
      cervical spinal cord were studied in cats. 2. Following implantation of HRP
      pellets into the spinal gray matter (C1-C3) or in the ponto-medullary reticular
      formation, the nucleus reticularis pontis caudalis (NRPC) or in the nucleus
      reticularis gigantocellularis (NRG), numerous neurones were retrogradely labelled
      in FFH on the ipsilateral side. In the former cases, the sizes of labelled
      neurones were medium-large (20-40 microns in diameter) while both small and
      medium-large neurones were labelled in the latter cases. 3. The lowest levels of
      spinal projection of single FFH neurones (n = 70) were assessed by antidromic
      spikes elicited by stimulating electrodes placed in C1, C3 and C7. The majority
      (59%) projected to C1 (but not to C3), about 27% to C3 (but not to C7), and only
      14% to C7. 4. Axonal trajectories of single FFH neurones in C1-C3 segments were
      investigated by antidromic threshold mapping methods. The stem axons of spinal
      projecting FFH neurones descended in the ventral or in the ventrolateral funiculi
      and the collaterals were projected to neck motor nuclei (lamina IX, Rexed 1954)
      and laminae V-VIII. The conduction velocities were estimated as 8-37 m/s from the
      antidromic latencies. 5. Axonal trajectories of 7 FFH neurones were investigated
      in the ponto-medullary reticular formation. All were antidromically activated
      from C1. In six neurones, the stem axons were located in the ventral part of the
      central tegmental tract and collaterals were projected to the NRPC and/or the
      NRG. Some of them projected to the inferior olive and the nucleus prepositus
      hypoglossi as well. The stem axon, in the remaining cell, was in the most dorso
      medial part of the medial longitudinal fasciculus and collaterals were projected
      mainly to the dorsal part of the NRPC and the NRG, and also to the medial
      vestibular nucleus. 6. Anterograde transport of WGA-HRP injected into FFH
      revealed that in the upper cervical spinal cord, stem axons were found in the
      ventral funiculus and ventral part of the lateral funiculus. Collateral
      projections and presumed bouton-like deposits were observed in the laminae VI-IX,
      especially in their medial part. In the brain stem, dense bundles of the
      descending fibres were found in the central and the medial tegmental tracts and
      in the medial longitudinal fasciculus. FFH neurones projected densely to the
      caudal half of the NRPC and to the rostral half of the NRG.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1375166
TI  - Mono- and disynaptic pathways from Forel's field H to dorsal neck motoneurones in
      the cat.
AB  - 1. We analysed the synaptic actions produced by Forel's field H (FFH) neurones on
      dorsal neck motoneurones and the pathways mediating the effects. 2. Stimulation
      of ipsilateral FFH induced negative field potentials of several hundred
      microvolts with the latency of about 1.1 ms in the medial ponto-medullary
      reticular formation, being largest in the ventral part of the nucleus reticularis
      pontis caudalis (NRPC), and in the dorsal part of the nucleus reticularis
      gigantocellularis (NRG). 3. Stimulation of ipsilateral FFH induced excitatory
      postsynaptic potentials (EPSPs) in 90% (47/52) and inhibitory postsynaptic
      potentials (IPSPs) in 19% (10/52) of the reticulospinal neurones (RSNs) in the
      NRPC and the NRG. Latencies of the EPSPs and IPSPs were 0.7-3.0 ms, the majority
      of which were in the monosynaptic range. The monosynaptic connexions were
      confirmed by spike triggered averaging technique both in excitatory (n = 4) and
      inhibitory (n = 2) pathways. 4. Single stimulation of FFH induced EPSPs at the
      segmental latencies of 0.3-1.0 ms in neck motoneurones, which were clearly in the
      monosynaptic range. Repetitive stimulation of FFH produced marked temporal
      facilitation of EPSPs in neck motoneurones. The facilitated components of the
      EPSPs had a little longer latencies and their amplitude reached several times as
      large as that evoked by single stimulation in all the tested motoneurones. These
      facilitated excitations are assumed to be mediated by RSNs in the NRPC and NRG,
      since RSNs were mono- and polysynaptically fired by stimulation of FFH and they
      were previously shown to directly project to neck motoneurones. 5. EPSPs were
      induced in 91% (82/91) of motoneurones supplying m. biventer cervicis and
      complexus (BCC; head elevator), 10% (3/29) of motoneurones supplying m. splenius
      (SPL; lateral head flexor). Likewise, stimulation of FFH produced EMG responses
      in BCC muscles, while not in SPL muscle. Thus FFH neurones produce excitations
      preferentially in BCC motoneurones. 6. Systematic tracking in and around FFH
      revealed that the effective sites for evoking above effects were in FFH and
      extended caudally along their efferent axonal course. 7. These results suggested
      that FFH neurones connect with neck motoneurones (chiefly BCC, head elevator)
      mono-, di- and/or polysynaptically and are mainly concerned with the control of
      vertical head movements.

PMID- 1375167
TI  - Identification of the axon pathways which mediate functional recovery of a
      paralyzed hemidiaphragm following spinal cord hemisection in the adult rat.
AB  - Despite extensive neurophysiological work carried out to characterize the crossed
      phrenic phenomenon, relatively little is known about the morphological substrate
      of this reflex which restores function to a hemidiaphragm paralyzed by spinal
      cord injury. In the present study WGA-HRP was injected into normal and
      functionally recovered hemidiaphragm muscle in rats during the crossed phrenic
      phenomenon. The retrograde transynaptic transport characteristics of WGA-HRP was
      utilized to delineate the source of the neurons which mediate the crossed phrenic
      phenomenon. The results indicated that the neurons which drive phrenic
      motoneurons in spinal hemisected rats during the crossed phrenic phenomenon are
      located bilaterally in the rostral ventral respiratory group (rVRG) of the
      medulla. No transneuronal labeling of propriospinal neurons was noted in either
      normal or spinal-hemisected rats. Thus, propriospinal neurons do not relay
      respiratory drive to phrenic motoneurons. The neurons of the rVRG project
      monosynaptically to phrenic motoneurons. The present results suggest that both
      crossed and uncrossed bulbospinal pathways from the rVRG collateralize to both
      the left and right phrenic nucleic and functional recovery of a hemidiaphragm
      paralyzed by ipsilateral spinal cord hemisection is mediated by supraspinal
      neurons from both sides of the brain stem. These results are important to our
      complete understanding of the mechanisms which govern motor recovery in mammals
      following spinal cord injury.

PMID- 1375168
TI  - Morphometric analysis of the effects of antineoplastic drugs on mucosa of normal
      ileum and ileal anastomoses in rats.
AB  - Antineoplastic agents affect the healing of intestinal anastomoses. They often
      induce anorexia and diarrhea, possibly caused by morphological changes in the
      small intestinal mucosa. These changes were evaluated in the rat ileum. Animals
      in group I underwent only intestinal surgery while those in groups II and III
      underwent surgery on the third day of a 5-day course with cisplatin (in two
      different doses), bleomycin, and 5-fluorouracil. The parameters were: number of
      mitoses in crypts, crypt depth, villus height, width, and contour length,
      measured in the mucosa of primarily resected segments of the ileum and of the
      anastomotic area. Surgery yields an increased crypt depth and villus length in
      the anastomotic area without changing villus width. The changes in intestinal
      crypts precede those in villi. Antineoplastic drugs decrease crypt mitotic rate,
      villus height, width, and contour length. After cessation of antineoplastic
      chemotherapy mitotic activity increases. The shallower and shorter villi increase
      in width and length resulting in an increased villus contour length and area. A
      linear relation exists between villus contour length and villus height and width.
      Thus, antineoplastic polychemotherapy, dose-dependently, reduces and surgical
      trauma increases intestinal proliferative activity. However, the morphologic
      changes do not unequivocally explain possible metabolic disturbances causing
      retarded intestinal wound healing.

PMID- 1375169
TI  - Level of expression controls modes of gating of a K+ channel.
AB  - Several distinct subfamilies of K+ channel genes have been discovered by
      molecular cloning, however, in some cases the structural differences among them
      do not account for the diversity of K+ current types, ranging from transient A
      type to slowly inactivating delayed rectifier-type, as members within each
      subfamily have been shown to code for K+ channels of different inactivation
      kinetics and pharmacological properties. We show that a single K+ channel cDNA of
      the Shaker subfamily (ShH4) can express in Xenopus oocytes not only a transient A
      type K+ current but also, upon increased level of expression, slowly inactivating
      K+ currents with markedly reduced sensitivity to tetraethylammonium. In
      correlation with the macroscopic currents there are single-channel gating modes
      ranging from the fast-inactivation mode which underlies the transient A-type
      current, to slow-inactivation modes characterized by bursts of longer openings,
      and corresponding to the slowly inactivating macroscopic currents.

PMID- 1375170
TI  - A large conductance ion channel in the nuclear envelope of a higher plant cell.
AB  - To detect and characterize ion channel activity in the nuclear envelope of a
      higher plant cell, we performed patch clamp experiments on nuclei isolated from
      coconut endosperm cells and on giant liposomes containing nuclear envelope
      fragments prepared from the same cells. An ion channel exhibiting a number of
      conductance substates, with a maximum of ca. 1,000 pS, was observed. Above an
      applied potential of +/- 100 mV, the behavior of the channel was similar in
      isolated nuclei and liposomes, indicating that both patch clamp modes were
      detecting the same channel. That such a channel has now been identified in
      members of both the animal and plant kingdoms reinforces the notion that the
      nuclear pores are not always open to ions.

PMID- 1375171
TI  - Solution structure of FK506 bound to FKBP-12.
AB  - The complex of the immunosuppressant FK506 bound to FKBP-12 has been studied in
      solution using 1H and inverse-detected 13C NMR methods. The resonances of bound,
      13C-labelled FK506 were assigned and a set of 66 intraligand NOE distance
      restraints were used to calculate the structure of the bound ligand by distance
      geometry and restrained molecular dynamics methods. The structure of bound FK506
      in solution closely resembles that seen in the X-ray structure [17], except for
      the allyl region. The differences reflect the influence of intermolecular crystal
      contacts and have implications for interpretation of the interaction of the
      FK506/FKBP complex with its putative biological receptor.

PMID- 1375172
TI  - Testosterone induction of poly(A)(+)-RNA synthesis and [35S]methionine
      incorporation into proteins of Rana esculenta Harderian gland.
AB  - The role of androgens in the cyclic secretory activity of the Rana esculenta
      Harderian gland (HG) was studied. Total RNA showed a dramatic increase in October
      and May when the nuclear androgen receptors peak. During the resumption of the
      secretory activity a gradual increase of poly(A)(+)-RNA was detected; during the
      enhancement phase (May) a peak of the poly(A)(+)-RNA fraction was found. In in
      vitro experiments testosterone increased the incorporation of [3H]uridine into
      the poly(A)(+)-RNA fraction and also that of [35S]methionine into a newly
      synthesized protein fraction (100 kDa). The latter effect is prevented by the
      exposure of the cells to the antiandrogen, cyproterone acetate (CPA). These
      findings reveal that, besides hamsters, the HG is a target for androgens in the
      frog.

PMID- 1375173
TI  - Manipulation of intracellular calcium affects in vitro juvenile hormone synthesis
      by larval corpora allata of Manduca sexta.
AB  - The effect of altering intracellular free Ca2+ on juvenile hormone (JH) and acid
      synthesis by larval and pupally-committed corpora allata (CA) of fifth stadium
      Manduca sexta was investigated. Larval CA required extracellular Ca2+ greater
      than or equal to 0.1 mM for maximal JH synthesis, while JH acid synthesis by
      glands after pupal commitment was independent of extracellular Ca2+. Free Ca2+ in
      the hemolymph ranged from 1.4 to 2.1 mM during the fifth stadium. Both calcium
      ionophores and caffeine, which releases Ca2+ from intracellular stores, inhibited
      JH synthesis by larval CA but stimulated JH acid synthesis by post-commitment CA.
      These results suggest that intracellular stores may be the principal source of
      Ca2+ for the biosynthetic activity of the post-commitment gland. Calcium channel
      blockers (La3+, Cd2+) and antagonists (verapamil, isradipine and nitrendipine)
      decreased both JH and JH acid synthesis, indicating the existence of Ca2+
      channels in the CA cell membrane. Calmodulin (CaM) antagonists inhibited the
      activity of both larval and post-commitment CA, suggesting an integral
      relationship of CaM to the effects of Ca2+ on gland activity. One of these
      effects is the demonstrated requirement of 0.1 mM extracellular Ca2+ for
      allatostatin inhibition of JH I synthesis by larval CA.

PMID- 1375174
TI  - Inhibition of adrenocortical steroidogenesis by alpha 2-macroglobulin is caused
      by associated transforming growth factor beta.
AB  - alpha 2-Macroglobulin (alpha 2M) is the major protein secreted by bovine
      adrenocortical cells in primary culture and its synthesis is stimulated by
      transforming growth factor beta (TGF beta). We investigated here the effects of
      alpha 2M on adrenocortical steroidogenesis. We observed that commercial
      preparations of bovine plasma alpha 2M were able to mimic the inhibitory action
      of TGF beta on adrenocortical cortisol production, with the same specificity of
      action directed at the steroid 17 alpha-hydroxylation step. This inhibition was
      time-dependent and dose-dependent (50% inhibition observed with 2 mg/ml alpha
      2M). Acid/ethanol extracts of alpha 2M appeared to retain the full inhibitory
      activity of alpha 2M. Anti-TGF beta antibodies could reverse the inhibition
      caused by the acid/ethanol extract but not that caused by native alpha 2M. Taken
      together, these results indicate that the inhibition of adrenocortical
      steroidogenesis induced by alpha 2M is caused by associated TGF beta. We
      estimated that 2 mg of alpha 2M contained approximately 0.1 ng of TGF beta,
      corresponding to a molar ratio of 1/700,000 between TGF beta and alpha 2M. These
      results also clearly indicate that the alpha 2M-TGF beta complexes are
      biologically active on adrenocortical cells, suggesting that these cells possess
      the enzymatic equipment that can activate the latent alpha 2M-TGF beta complexes.

PMID- 1375175
TI  - Stimulus-secretion coupling in beta-cells of transplantable human islets of
      Langerhans. Evidence for a critical role for Ca2+ entry.
AB  - With human islets isolated for transplantation, we examined the applicability to
      humans of a metabolic fuel hypothesis of glucose transduction and a Ca2+
      hypothesis of depolarization-secretion coupling, both previously proposed for
      rodent islet beta-cells. We report that several features of human beta-cell
      physiology are well accounted for by these hypotheses. With whole-islet
      perifusion, we demonstrated that insulin secretion induced by glucose,
      tolbutamide, or elevated K+ is dependent on extracellular Ca2+. Insulin release
      induced by these secretagogues is enhanced by the dihydropyridine Ca2+ channel
      agonist BAYk8644 and depressed by the dihydropyridine Ca(2+)-channel antagonist
      nifedipine. All of the aforementioned secretagogues provoke increases in
      cytosolic free Ca2+, which are dependent on extracellular Ca2+ and are altered by
      the dihydropyridine drugs. Individual beta-cells in the islet display diminished
      resting membrane conductance, graded depolarization, and complex electrical
      patterns, including bursts of action potentials in response to stimulatory
      concentrations of glucose or tolbutamide. Individual islet beta-cells display
      voltage-dependent Ca2+ currents that are activated at membrane potentials
      traversed during the excursion of the action potential. In most cells, the Ca2+
      currents are enhanced by BAYk8644 and depressed by nifedipine at concentrations
      that have parallel effects on secretagogue-induced increases in cytosolic Ca2+
      and insulin secretion. These survey studies should provide the basis for more
      detailed investigations of the relationship of voltage-dependent ionic currents
      to electrical activity patterns and of electrical activity patterns to granule
      exocytosis in single human beta-cells.

PMID- 1375176
TI  - Developmental regulation of amylin and insulin-gene expression in lean (Fa/Fa)
      and obese (fa/fa) Zucker rats.
AB  - Obese individuals are hyperinsulinemic and insulin resistant. Because amylin is
      cosecreted with insulin and may contribute to the insulin resistance of obesity,
      this study tested the hypothesis that insulin and amylin genes are coordinately
      regulated by obesity and carbohydrate feeding. Insulin and amylin gene expression
      were measured during the suckling/weaning transition in lean (Fa/Fa) and obese
      (fa/fa) Zucker rats, a period associated with marked changes in tissue insulin
      sensitivity. There was a decline in insulin mRNA (-90 +/- 15%, P less than 0.01)
      and amylin mRNA (-72 +/- 21%, P less than 0.01) content in pancreases of lean
      rats maintained on a high-fat diet from days 15 to 30, probably reflecting the
      relative increase in exocrine/endocrine development during this neonatal period
      and the effects of fat feeding. Weaning on high-carbohydrate versus high-fat
      diets resulted in enhanced expression of both insulin (P less than 0.05) and
      amylin (P less than 0.05) mRNAs. In contrast to the decline in pancreatic insulin
      and amylin mRNA content observed in lean rats, there was an increase in insulin
      mRNA (421.3 +/- 57.5%, P less than 0.05) and no change in amylin mRNA in obese
      rats maintained on a high-fat diet from days 15 to 30. There was no enhancement
      of insulin or amylin gene expression in obese rats with high carbohydrate
      relative to high-fat feeding, perhaps reflecting maximum rates of transcription
      in these obese insulin-resistant rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375177
TI  - Histamine inhibits 5-hydroxytryptamine release from the porcine small intestine:
      involvement of H3 receptors.
AB  - Strips of the porcine small intestine were incubated in vitro, and the release of
      5-hydroxytryptamine (5-HT) was determined by high-pressure liquid chromatography
      with electrochemical detection. Removal of the mucosa resulted in a large
      reduction (95%) of tissue 5-HT, suggesting that enterochromaffin cells are the
      main source of 5-HT. The release of 5-HT was reduced by 70% after omission of
      calcium. Tetrodotoxin and hexamethonium reduced the release of 5-HT by 30%-40% in
      a nonadditive manner, indicating a spontaneous neuronal (nicotinic) excitatory
      input to the enterochromaffin cells. Histamine inhibited the release of 5-HT by
      about 50%. This effect was not affected by mepyramine or cimetidine but was
      effectively blocked by thioperamide, indicating the involvement of H3 receptors.
      The selective H3-receptor agonist R-alpha-methyl-histamine also inhibited 5-HT
      release. Because the effect of R-alpha-methyl-histamine was also observed in the
      presence of tetrodotoxin, an indirect, neuronally mediated action could be
      excluded. Therefore, the inhibitory H3 receptors may be localized directly at the
      enterochromaffin cells.

PMID- 1375178
TI  - Increased levels of substance P in the myenteric plexus of Trichinella-infected
      rats.
AB  - Changes in immunoreactive substance P concentrations were investigated in
      longitudinal muscle-myenteric plexus preparations from the inflamed jejunum of
      Trichinella spiralis-infected rats. The substance P concentration increased
      within 2 days of infection and increased fivefold by day 6; in contrast, there
      was no significant increase in substance P in the noninflamed ileum. In vitro
      exposure of preparations from infected rats to scorpion venom reduced substance P
      levels by 88%. In addition, no increase in substance P was observed in rats that
      had been treated with capsaicin as neonates or as adults before infection.
      Treatment of infected rats with betamethasone attenuated the inflammatory
      response to the infection and prevented the increase in substance P. Furthermore,
      no significant increase in substance P concentration was seen in congenitally
      athymic rats infected with T. spiralis. This study is consistent with the
      hypothesis that inflammation increases substance P in myenteric nerves by a
      process that involves T lymphocytes.

PMID- 1375179
TI  - Truncated and native insulinlike growth factor I enhance mucosal adaptation after
      jejunoileal resection.
AB  - It has been shown previously that insulinlike growth factors (IGFs) stimulate the
      proliferation of intestinal crypt cells in vitro. To examine the in vivo effects
      of IGF-I on mucosal adaptation, three groups of Sprague-Dawley rats underwent 80%
      jejunoileal resection. Miniosmotic pumps were then inserted under the skin
      immediately after resection to deliver vehicle (resected control), 1.5 mg/kg per
      day of IGF-I, or 1.5 mg/kg per day of des-(1-3)-IGF-I (des-IGF-I). Des-IGF-I is a
      truncated form of IGF-I that binds as well to type I IGF receptors but less
      tightly to several forms of IGF-binding proteins (IGFBPs) than IGF-I. Ad libitum
      food intake did not differ among the three resected groups. Body weight gains
      were greater in animals receiving des-IGF-I than in those receiving IGF-I, which
      were greater than resected controls. All animals were killed 7 days
      postoperatively, and the remaining small intestine was removed and divided at the
      anastomotic site. Both IGF-I and des-IGF-I induced hyperplasia (increased DNA and
      protein content) in the duodenojejunum but not in the ileum. IGF-I and des-IGF-I
      were equally active. In contrast, sucrase, maltase, and leucine aminopeptidase
      activities were greater only in the ileum of animals receiving IGF-I and des-IGF
      I than in resected controls. Although more potent in stimulating overall body
      weight gain, des-IGF-I was not more potent than IGF-I when duodenal and ileal
      responses were determined. IGF infusion (IGF-I greater than des-IGF-I) increased
      the levels of circulating IGFBP-3 and IGFBP-2, which may act to modulate the
      biological effectiveness of the infused peptides. These results suggest that both
      IGF-I and des-IGF-I may have potential as therapeutic agents for short bowel
      patients.

PMID- 1375180
TI  - Intrahepatic bile duct loss in biliary atresia despite portoenterostomy: a
      consequence of ongoing obstruction?
AB  - The histological and immunohistochemical characteristics of the liver in 44
      children (28 boys, 16 girls) with extrahepatic biliary atresia at different
      stages of the clinical course were studied. Thirty-four wedge liver biopsy
      specimens taken during Kasai operations (25 specimens) and relaparotomy (9
      specimens) and 20 hepatectomy explants taken at the time of transplantation were
      examined. Routine histological stains and monoclonal antibodies against different
      molecular weight cytokeratins and HLA-DR were used. The histopathological changes
      and the pattern of cytokeratin expression observed during the course of the
      disease were suggestive of persistent or recurrent extrahepatic biliary
      obstruction that occurred despite the Kasai operation and eventually led to
      cirrhosis and liver failure. Quantitative studies showed a progressive loss of
      intrahepatic bile ducts over the time course of the disease. This destruction of
      bile ducts had a geographic anatomical distribution in hepatectomy specimens, and
      in two livers it occurred predominantly in only one lobe. This geographic
      distribution of the vanishing bile ducts probably indicates an unpredictable and
      uneven obliteration of bile ducts in the porta hepatis during portoenterostomy
      wound healing and scarring.

PMID- 1375181
TI  - Construction and characterization of an Escherichia coli mutant deficient in the
      metY gene encoding tRNA(f2Met): either tRNA(f1Met) or tRNA(f2Met) is required for
      cell growth.
AB  - The Escherichia coli metY gene, encoding tRNA(f2Met), was split by the kanamycin
      resistance-encoding gene. The resulting mutant exhibited the same growth rate as
      the wild type, indicating that tRNA(f2Met) is not indispensable as is the case
      with the metZ gene encoding tRNA(f1Met) [Kenri et al., Gene 103 (191) 31-36].
      beta-Galactosidase was produced efficiently from the start codon AUG of the
      intact lacZ gene or a trpA'::lac'Z fusion gene, in the metY mutant. The lac
      repressor from the lacI gene and the chimeric protein from a hupB'::lac'Z fusion
      gene, whose start codons are GUG, were also synthesized efficiently in the
      insertion mutant. These results provide evidence that tRNA(f2Met) is not
      essential for growth of E. coli and that the start codons, AUG and GUG, are both
      recognized by tRNA(f1Met), a major N-formyl methionine-specific tRNA, in the
      tRNA(f2Met)-depleted cells. We were unable to construct mutants deficient in both
      tRNA(f1Met) and tRNA(f2Met) by P1 phage-mediated transduction with the metY and
      metZ mutations. Moreover, the ampicillin-resistance marker of the pUC9 plasmid
      carrying metZ+ was not cured at 42 degrees C in host cells with the polAts and
      metY-metZ double mutations. These results indicate that either tRNA(f1Met) or
      tRNA(f2Met) is required for the growth of E. coli.

PMID- 1375183
TI  - Interactions between parents and pediatric primary care physicians about
      children's mental health.
AB  - Interaction patterns between parents and pediatricians were examined during 1,378
      well-child visits to four public and private pediatric clinics. During 327
      visits, parents listed at least one psychosocial concern related to their child's
      mental health. At 37 percent of these visits, parents said they did not wish to
      discuss the concern with the physician. Physicians failed to address concerns
      during approximately 35 percent of visits at which parents were willing to
      discuss them. Successful parent-physician interactions were three times more
      frequent in private practices than in a public clinic; they were more likely when
      fewer concerns were stated and less likely when behavior problems were the
      concern. Parents concerned about the parent-infant relationship were four times
      more likely to be referred to outside mental health services, although these
      cases were relatively rare. Older children and families receiving Medicaid were
      also more likely to be referred to such services.

PMID- 1375182
TI  - Corrected nucleotide sequence of M13mp18 gene III.
AB  - There are seven differences between the actual nucleotide (nt) sequence of
      bacteriophage M13mp18 gene III and the previously reported nt sequence (which had
      been compiled based on the nt sequence of wild-type bacteriophage M13 gene III).

PMID- 1375185
TI  - Localization of the human insulin-like growth-factor-binding protein 4 gene to
      chromosomal region 17q12-21.1.
AB  - Insulin-like growth-factor-binding proteins (IGFBPs) constitute a family of
      structurally related proteins that specifically bind insulin-like growth factors
      and modulate their functions. In this study, the chromosomal localization was
      determined for the gene encoding IGFBP4, i.e. inhibitory-IGFBP. A polymerase
      chain reaction (PCR) fragment corresponding to the previously published cDNA
      sequence was used to isolate overlapping cosmid clones. By fluorescent in situ
      hybridization to metaphase chromosomes, the IGFBP4 gene was then localized to
      chromosomal region 17q21-21.1. This result was in agreement with PCR analysis of
      a panel of somatic cell hybrids.

PMID- 1375184
TI  - Variation in gene copy number and polymorphism of the human salivary amylase
      isoenzyme system in Caucasians.
AB  - The polymorphic patterns of human salivary amylase of a large number of
      individuals of Caucasian origin were determined by using isoelectric focusing and
      polyacrylamide gel electrophoresis. Nine different salivary amylase protein
      variants were found; three of them are recorded for the first time and their
      heredity is shown. Some of the variants are encoded by haplotypes expressing
      three allozymes. Most variants display low frequencies. Analysis of the relative
      intensities of variant-specific isozyme bands, combined with segregation
      analysis, show that extensive quantitative variation is present in the
      population. The numbers of salivary amylase genes in some families showing
      quantitative variation at the protein level have been estimated by the polymerase
      chain reaction. We present evidence that quantitative variations in amylase
      protein patterns do not always reflect variations in gene copy number but that
      other mechanisms are also involved.

PMID- 1375186
TI  - The occurrence of various non-delta F508 CFTR gene mutations among Hungarian
      cystic fibrosis patients.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease caused by different
      mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
      The frequency of the major mutation (delta F508) in the Hungarian population is
      64%. To identify other common mutations in CF families from Hungary, 30 non-delta
      F508 CF chromosomes were analyzed for selected mutations in exon 11 (G551D,
      R553X, G542X), intron 4 (621 + 1G----T), intron 10 (1717-1G----A), exon 20
      (W1282X), and in exon 21 (N1303K) of the CFTR gene. In 6 of the 30 non-delta F508
      CF chromosomes the following mutations were detected: R553X, G542X, 1717-1G----A,
      W1282X, and N1303K. After analysis of the above eight mutations, 30% of CF
      chromosomes are as yet undefined and further analysis is planned.

PMID- 1375187
TI  - "Self" to cytotoxic T cells has to be 1,000 or less high affinity nonapeptides
      per MHC antigen.
AB  - In order to serve as the effective target of a relevant cytotoxic T-cell
      receptor, the same peptide fragment has to occupy at least 0.1% of the class I
      major histocompatibility complex (MHC) antigen sites on the plasma membrane.
      Because of this need, I content that the thymic educator cell of "self" to
      cytotoxic T cells can suppress autoreactive T-cell clones only with regard to at
      the most, 1,000 self nonapeptides per a given allelic form of class I MHC
      antigens; e.g., HLA-A2. Each allelic form of class I MHC antigen apparently
      developed the preferential binding affinity toward a specific set of
      nonapeptides. The requirement for preferential binding can either be permissive
      or stringent. In the case of human HLA-A2, those nonapeptides having either Leu
      or Met at the second position and mainly Val, but occasionally Leu at the ninth
      position are preferred. Since both Leu and Val are very common residues, the
      typical somatic cell type readily supplies nearly 3000 high affinity host
      nonapeptides preferred by HLA-A2. Of those, the tolerance can be induced, at the
      most, to only 1,000 nonapeptides. In view of this, permissive class I MHC
      antigens such as HLA-A2 carefully avoid high affinity nonapeptides in viral
      proteins, for their status as to self or nonself is uncertain, and they choose
      second choice nonapeptides as T epitopes. In sharp contrast to human HLA-A2,
      mouse H-2Db represents the stringent class I MHC antigens. In order to show the
      high binding affinity toward H-2Db, nonapeptides are required to carry Asn at
      position 5 and Met or Ile at the equally critical position 9. Inasmuch as Asn and
      Met are rare residues and Ile, too, is not a common residue, the typical somatic
      cell type can supply only several hundred host nonapeptides having the high
      binding affinity toward H-2Db. Under the circumstance, there is no problem in
      memorizing the selfness of all of them. Accordingly, T epitopes are almost
      invariably chosen from the high affinity nonapeptides that are present in their
      viral proteins.

PMID- 1375188
TI  - Immunoreactivity of recombinant carcinoembryonic antigen proteins expressed in
      Escherichia coli.
AB  - Immunoreactivities of recombinant carcinoembryonic antigen (CEA) proteins
      expressed in Escherichia coli (E. coli) were analyzed in relation to the CEA
      domain structure [domains N, I (A1-B1), II (A2-B2), III (A3-B3) and M]. We
      reconstructed in a prokaryotic expression vector, pUCPL-cI, the cDNAs fro CEA-N,
      CEA-I, CEA-II, and CEA-III-M. The latter three were expressed as fusion products
      with bacterial beta-galactosidase. The recombinant proteins were solubilized by
      sonication in 1% sodium dodecyl sulfate (SDS) and purified by preparative SDS
      polyacrylamide gel electrophoresis followed by electroelution. Their molecular
      weights judged from Western blotting coincided with those calculated from their
      cDNA sequences, respectively. By solid-phase enzyme immunoassays, the
      immunoreactivities of the purified recombinant proteins were tested with 21
      distinct anti-CEA monoclonal antibodies (MAbs) which had been found to recognize
      the peptide epitopes of the CEA molecule and to be reactive with the recombinant
      CEA proteins expressed in Chinese hamster ovary (CHO) cells. Fourteen of the 21
      MAbs reacted with the recombinant CEA proteins expressed in E. coli and confirmed
      the localization of the epitopes identified by using the recombinant CEA proteins
      expressed in CHO cells. The reactivities of 5 MAbs with the recombinant proteins
      expressed in E. coli were remarkably low when compared with those of the proteins
      expressed in CHO cells but also confirmed the localization of the epitopes
      identified with the recombinant CEA proteins expressed in CHO cells. The
      remaining 2 MAbs did not react with any recombinant protein expressed in E. coli.
      These results indicate that the fusion CEA-proteins expressed in E. coli are
      useful in the localization of the epitopes on the polypeptide chains when they
      reacted with the MAbs tested. However, one third of the epitopes of CEA peptides
      may be profoundly affected by the presence of disulfide bonds and/or sugar chains
      which do not seem to be formed well in E. coli.

PMID- 1375189
TI  - FKBP-12 is not an inhibitor of protein kinase C.
AB  - It was recently noted that the amino acid sequence of FK506 binding protein (FKBP
      12) is nearly identical to that of an endogenous inhibitor of protein kinase C,
      PKCI-2. To follow up on this observation, we have tested the hypothesis that FKBP
      12 is an inhibitor of PKC. The kinase activity of rat brain protein kinase C
      (PKC) was not inhibited by the presence of up to 700 micrograms recombinant human
      FKBP-12 per ml, in either the presence or absence of FK506. FKBP-12 also did not
      affect PMA-induced phosphorylation of an endogenous PKC substrate, an 80 kDa
      protein, in permeabilized cells. To test whether FKBP-12 could account for
      endogenous PKC inhibitory activity in cells, Jurkat cell lysate was
      chromatographed on an anion exchange column. A peak of PKC inhibitory activity
      was eluted at approximately 200 mM NaCl. As shown by both Western blots and FK506
      binding activity, FKBP-12 was eluted only in the flow-through and wash fractions.
      These results demonstrate that FKBP-12 is clearly distinct from endogenous PKC
      inhibitory activity.

PMID- 1375190
TI  - Rumpshaker: an X-linked mutation causing hypomyelination: developmental
      differences in myelination and glial cells between the optic nerve and spinal
      cord.
AB  - The X-linked mutation rumpshaker (rsh), which is probably an allele of jimpy
      (jp), causes hypomyelination in the CNS of mice. This study examines the
      developmental expression of the morphology, glial cells, and immunostaining of
      myelin proteins in the optic nerve and spinal cord. The optic nerve contains
      varying numbers of amyelinated and myelinated fibres. The majority of such
      sheaths are of normal thickness whereas in the spinal cord most axons are
      associated with a disproportionately thin sheath which changes little in
      thickness during development. In the optic nerve glial cell numbers are elevated
      in mutants during early and peak myelination but then fall slightly below normal
      in adults. In contrast, the number of glial cells is consistently elevated after
      16 days of age in the spinal cord. The majority of the alterations to total glial
      cells are due to corresponding changes in the oligodendrocyte population.
      Immunostaining intensity is somewhat reduced for myelin basic protein (MBP) and
      the C-terminal common to proteolipid protein (PLP) and DM-20 and profoundly
      decreased for the PLP-specific peptide. Glial fibrillary acidic protein (GFAP) is
      increased in rsh. It is probable that some of the variation in myelination
      between optic nerve and cord in rsh is related to the difference in axon diameter
      in the two locations, as there are adequate numbers of oligodendrocytes at the
      time of myelination. However, the effect of the mutation on cell development in
      the brain and the spinal cord may be different. The immunostaining indicates a
      marked deficiency in PLP in myelin but suggests that DM-20 levels may be
      relatively normal. rsh shows several major differences from jp and other X-linked
      myelin mutants, particularly in relation to oligodendrocyte numbers, and will be
      useful to elucidate the role of the PLP gene in influencing oligodendrocyte
      differentiation and survival.

PMID- 1375191
TI  - Developmental appearance, antigenic profile, and proliferation of glial cells of
      the human embryonic spinal cord: an immunocytochemical study using dissociated
      cultured cells.
AB  - We have investigated the time of appearance of the earliest differentiating glial
      cell types of human spinal cord using a panel of antigenic markers to identify
      them in cultures from 6- to 9-week-old human embryos. Immunolabeling performed at
      14 h in vitro with the O4 mAb, an early oligodendrocyte marker, showed the
      presence of oligodendrocytes during the 7th week of age. At 8 weeks only a few of
      the O4+ cells expressed galactocerebroside (GalC), a marker of more
      differentiated oligodendrocytes. All the O4+ and GalC+ cells were vimentin+ and
      some of the GalC+ cells were A2B5+, GD3+ and SSEA-1+. During the first week in
      vitro many of the O4+ cells exhibiting a more immature, bi- or tri-polar
      morphology incorporated [3H]thymidine into their nuclei. Cells expressing the
      astrocyte-specific marker GFAP could be first observed at 8 weeks; almost all of
      these GFAP+ cells, which should correspond to radial glia on the basis of the
      current literature, were vimentin+, A2B5+, GD3+, and SSEA-1+. At 2 days in vitro
      incorporation of [3H]thymidine could be shown in a small fraction of these cells.
      The finding that radial glia and oligodendrocytes expressed similar antigenic
      features and the additional observation that a small, but consistent fraction of
      the cells were simultaneously labeled by O4 and anti-GFAP antibodies support the
      hypothesis that, in the human spinal cord, radial glial cells can give rise to
      both oligodendrocytes and astrocytes; in this respect, radial glial cells may be
      similar to the A2B5+, GD3+, vimentin+ bipotential glial progenitors previously
      identified in cultures from developing rat CNS, which also express A2B5, GD3, and
      vimentin.

PMID- 1375192
TI  - Heme oxygenase is a heat shock protein and PEST protein in rat astroglial cells.
AB  - Cultured rat forebrain astrocytes contained significant amounts of
      immunostainable heme oxygenase-1 (HO-1) isozyme, whereas HO-1 was undetectable in
      spontaneously transformed rat astroglial cells (ATs). HO-1 was inducible in both
      cell types by heat shock and by submicromolar amounts of H2O2. Inhibition of RNA
      synthesis with actinomycin D or protein synthesis with cycloheximide resulted in
      the rapid loss of immunostainable heme oxygenase in astrocytes. Analysis of the
      primary structure of heme oxygenase suggests that it is a PEST protein, i.e.,
      targeted for rapid turnover.

PMID- 1375193
TI  - Analysis of Escherichia coli colonization factor antigen I linear B-cell
      epitopes, as determined by primate responses, following protein sequence
      verification.
AB  - Colonization factor antigen I (CFA/I)-bearing strains of enterotoxigenic
      Escherichia coli (ETEC) are responsible for a significant percentage of ETEC
      diarrheal disease worldwide whether the disease presents as infant diarrhea with
      high mortality or as traveler's diarrhea. CFA/I pili (fimbriae) are virulence
      determinants that consist of repeating protein subunits (pilin), are found in
      several ETEC serogroups, and promote attachment to human intestinal mucosa. While
      CFA/I pili are highly immunogenic, the antigenic determinants of CFA/I have not
      been defined. We wished to identify the linear B-cell epitopes within the CFA/I
      molecule as determined by primate response to the immunizing protein. To do this,
      we (i) resolved the discrepancies in the literature on the complete amino acid
      sequence of CFA/I by N-terminal and internal protein sequencing of purified and
      selected proteolytic fragments of CFA/I, (ii) utilized this sequence to
      synthesize 140 overlapping octapeptides covalently attached to polyethylene pins
      which represented the entire CFA/I protein, (iii) immunized three rhesus monkeys
      with multiple intramuscular injections of purified CFA/I subunit in Freund's
      adjuvant, and (iv) tested serum from each monkey for its ability to recognize the
      octapeptides in a capture enzyme-linked immunosorbent assay. Eight linear B-cell
      epitopes were identified; the region containing an epitope at amino acids 11 to
      21 was strongly recognized by all three individual rhesus monkeys, while the
      amino acid stretches 22 to 29, 66 to 74, 93 to 101, and 124 to 136 each contained
      an epitope that was recognized by two of the three rhesus monkeys. The three
      other regions containing epitopes were recognized by one of the three
      individuals. The monkey antiserum to pilus subunits recognized native intact pili
      by immunogold labeling of CFA/I pili present on whole H10407 cells. Therefore,
      immunization with pilus subunits induces antibody that clearly recognizes both
      synthetic linear epitopes and intact pili. We are currently studying the
      importance of these defined epitope-containing regions as vaccine candidates.

PMID- 1375194
TI  - Characterization of the epitope specificity of murine monoclonal antibodies
      directed against lipid A.
AB  - A series of monoclonal antibodies directed against lipid A was characterized by
      using synthetic lipid A analogs and partial structures. These compounds vary in
      phosphate substitution, acylation pattern (type, number, and distribution of
      fatty acids), and, in the case of monosaccharides, in their backbone glycosyl
      residue. The monoclonal antibodies tested could be subdivided into five groups
      according to their reactivity patterns. One group reacted exclusively with 1,4'
      bisphosphoryl lipid A, and a second also reacted with 4'-monophosphoryl lipid A.
      Two further groups recognized either 4-phosphoryl or 1-phosphoryl monosaccharide
      partial structures of lipid A. The fifth group reacted with 4-phosphoryl
      monosaccharide structures and with phosphate-free compounds. Antibodies reactive
      with monosaccharide structures also recognized their epitopes in corresponding
      phosphorylated disaccharide compounds. Both groups of monosaccharide and
      monophosphoryl lipid A-recognizing antibodies have access to their epitopes in
      bisphosphoryl compounds as well. Because of this unidirectional reactivity with
      more complex structures, the various specificities cannot be distinguished by
      using bisphosphoryl lipid A (e.g., Escherichia coli lipid A) as a test antigen.
      The epitopes recognized by the various monoclonal antibodies all reside in the
      hydrophilic backbone of lipid A, and there was no indication that fatty acids
      were part of the epitopes recognized. Nevertheless, the reactivities of compounds
      in the different test systems are strongly influenced by their acylation
      patterns; i.e., acyl groups may modulate the exposure of lipid A epitopes.

PMID- 1375195
TI  - Rat monoclonal antibodies against Aspergillus galactomannan.
AB  - Monoclonal antibodies (MAbs) against Aspergillus fumigatus galactomannan were
      produced in rats. Seven of them, EB-A1 through EB-A7, were characterized in more
      detail. They were all immunoglobulin M antibodies, reacting in an indirect enzyme
      linked immunosorbent assay with purified A. fumigatus galactomannan, with avidity
      constants of between 2 x 10(9) and 5 x 10(9)/M. Enzyme-linked immunosorbent assay
      inhibition experiments with modified galactomannan and synthetic oligomers of
      beta (1----5)galactofuranose demonstrated that the MAbs bound to an epitope
      located on the beta(1----5)galactofuranose-containing side chains of the
      galactomannan molecule. An identical or similar epitope also seemed to be present
      in other fungi. Immunofluorescence and immunoelectron microscopy experiments with
      EB-A2 revealed the presence of the antigen in the fungal wall and inside the
      cell. Immunoblotting experiments demonstrated that the epitope recognized by the
      MAbs was a common oligosaccharide moiety of a wide range of intracellular and
      extracellular glycoproteins in A. fumigatus. The characteristics of the MAbs
      justify their use in the diagnosis of invasive aspergillosis by antigen
      detection.

PMID- 1375196
TI  - Monoclonal antibodies define genus-specific, species-specific, and cross-reactive
      epitopes of the chlamydial 60-kilodalton heat shock protein (hsp60): specific
      immunodetection and purification of chlamydial hsp60.
AB  - Ocular and urogenital tract infections with Chlamydia trachomatis can progress to
      chronic inflammatory diseases that produce blindness and tubal infertility. The
      pathophysiology of these chronic disease conditions is thought to be
      immunologically mediated, and the chlamydial 60-kDa heat shock protein (hsp60)
      has been implicated as a major target antigen that stimulates the
      immunopathological response. The lack of chlamydial hsp60 antibodies and purified
      hsp60 has severely restricted studies to define more thoroughly the role of this
      protein in the immunopathogenesis of chlamydial disease. We produced a panel of
      antichlamydial hsp60 monoclonal antibodies (MAbs) and defined their specificities
      by immunoblotting against lysates of C. trachomatis, C. psittaci, and six other
      genera of bacteria. Three patterns of anti-hsp60 immunoreactivity were observed:
      chlamydial species specific, chlamydial genus specific, and cross-reactive. The
      epitopes recognized by these MAbs were localized within the primary amino acid
      sequence of hsp60 by immunoblotting against recombinant amino-terminal truncated
      hsp60 fusion polypeptides and then precisely mapped by use of overlapping
      synthetic peptides. The majority of the MAbs mapped to either the amino or the
      carboxyl termini of hsp60. Epitopes defining all three MAb reactivities mapped
      within amino-terminal residues 6 to 16. Genus-specific hsp60 MAbs mapped to
      epitopes located within this region and to residues 17 to 28 and 177 to 189.
      Antichlamydial hsp60 MAbs stained inclusions as effectively as MAbs specific for
      the major outer membrane protein. Homogeneous preparations of full-length
      recombinant chlamydial hsp60 and amino-terminal truncated recombinant hsp60
      polypeptides were obtained by immunoabsorption chromatography with an hsp60 MAb
      reactive to the carboxyl terminus of the protein. Thus, the antichlamydial MAbs
      described here should be extremely useful for the specific immunodetection of
      hsp60 in tissues from individuals having different disease manifestations and for
      the purification of hsp60 or truncated hsp60 polypeptides for use in serologic
      and lymphocyte proliferation assays. The availability of these MAbs will
      facilitate studies to define more precisely the role of hsp60 in the
      immunopathogenesis of chlamydial disease.

PMID- 1375197
TI  - Stage-specific expression and intracellular shedding of the cell surface trans
      sialidase of Trypanosoma cruzi.
AB  - We have used antibodies to the Trypanosoma cruzi trans-sialidase and to its
      product, the host cell invasion-related Ssp-3 epitope, to study the expression of
      the corresponding antigens during the intracellular development of the parasite
      and in the extracellular trypomastigotes. As soon as 2 h after host cell
      invasion, trans-sialidase was no longer detected, whereas the Ssp-3 epitope was
      still present on intracellular parasites. The amastigotes which subsequently
      developed remained nonreactive with the antibodies. Expression of enzymatically
      active T. cruzi trans-sialidase started again only after transformation of the
      amastigotes into trypomastigotes 72 h after host cell invasion. trans-Sialidase
      was shed from the trypanosomes into the host cell cytoplasm, where the enzyme
      accumulated until release of the parasites. All released trypomastigotes
      expressed trans-sialidase on their surfaces and in the flagellar pockets, but
      stumpy trypomastigotes were stained more intensely than slender trypomastigotes.
      Ssp-3, the sialylated reaction product of trans-sialidase, was assembled only
      after rupture of the host cell membrane and was detected on the plasma membranes
      and in the flagellar pockets of all trypomastigotes.

PMID- 1375198
TI  - Prolonged elevation of interleukin-8 and interleukin-6 concentrations in plasma
      and of leukocyte interleukin-8 mRNA levels during septicemic and localized
      Pseudomonas pseudomallei infection.
AB  - Patients suffering from serious bacterial infection present to the hospital after
      early inflammatory events, such as release of tumor necrosis factor (TNF), have
      been initiated. The role of other cytokines, such as interleukin-8 (IL-8), a
      neutrophil chemoattractant and activator, in the pathophysiology of human sepsis
      is not well characterized, and there are only limited data on IL-6. We studied
      serial concentrations of TNF, IL-6 (involved in the acute-phase response), and IL
      8 in plasma and leukocyte levels of mRNA for these cytokines in patients with
      localized and septicemic Pseudomonas pseudomallei infection on admission to the
      hospital and during a prolonged recovery phase (up to 30 days). Of 18 patients, 8
      had detectable plasma IL-8 and all had raised plasma IL-6 concentrations. In
      patients who died median initial concentration of IL-8 (167 pg/ml; range, 97 to
      362 pg/ml) and IL-6 (4,800 pg/ml; range, 60 to 9,245 pg/ml) in plasma were higher
      than those in survivors (P less than 0.008 and P = 0.007, respectively). Septic
      patients who survived and patients with localized disease had similar cytokine
      levels. Plasma IL-8 and IL-6 concentrations were elevated throughout the
      inpatient period of recovery. Circulating leukocytes contained mRNA for IL-8 but
      not for IL-6 and TNF, and they may secrete IL-8. An elevated plasma IL-6
      concentration (greater than 1,000 pg/ml) had 75% mortality) was the best
      predictor of mortality in P. pseudomallei sepsis. Fifty percent of patients with
      detectable plasma IL-8 concentrations died. In contrast, plasma TNF bioactivity
      did not relate to outcome; 75% of patients who did never had detectable plasma
      TNF activity.

PMID- 1375199
TI  - Localization of two epitopes recognized by monoclonal antibody PCG-4 on
      Clostridium difficile toxin A.
AB  - The toxin A gene of Clostridium difficile contains a 2.5-kb region encoding a
      series of contiguous repeating units located at the COOH terminus of the
      molecule. We previously showed that the monoclonal antibody (MAb) PCG-4, which
      neutralizes the enterotoxic activity of toxin A, binds to epitopes located within
      these repeating units. In the present study, we subcloned a series of fragments
      from this portion of the gene. The recombinant peptides expressed from the gene
      fragments were examined for reactivity with MAb PCG-4 to identify the epitopes
      involved in binding. Our results showed that MAb PCG-4 recognizes epitopes in
      amino acid residues 2097 through 2141 and amino acid residues 2355 through 2398.

PMID- 1375200
TI  - Role of specific determinants in mannan of Candida albicans serotype A in
      adherence to human buccal epithelial cells.
AB  - Candida albicans serotype A (C. albicans A) possesses a specific antigen,
      designated antigen 6, which resides in mannans on the cell surface. To determine
      the role of the mannan moiety of the C. albicans cell wall in adherence to buccal
      epithelial cells, we used antigen 6-deficient mutants which had been isolated by
      screening with an agglutinating monoclonal antibody against antigen 6 (MAb-6). 1H
      nuclear magnetic resonance spectral analysis of the purified mannans from the
      mutants showed a loss of the signals related to that beta-linkage of the side
      chains. Moreover, acetolyzed fragments of the mutant mannans showed a decreased
      amount of mannohexaose and mannopentaose. The mutant yeast cells exhibited
      significantly reduced ability to adhere both to exfoliated buccal epithelial
      cells and to a human buccal cell line. A number of strains of C. albicans A, C.
      tropicalis, and C. glabrata, all of which bear antigen 6, showed significantly
      higher adherence to the cell line than did those of C. albicans serotype B, which
      lack antigen 6. The whole mannan from the C. albicans A parent inhibited the
      adherence of C. albicans A to epithelial cells dose dependently, whereas mannan
      from a mutant strains did not. Moreover, C. albicans A treated with MAb-6 or
      polyclonal factor 6 serum showed reduced adherence. A close correlation was found
      between adhesive ability and agglutinability with MAb-6 in the C. albicans A
      parent, the antigenic mutants, and their spontaneous revertants. These results
      suggest that so far as mannan adhesion is concerned, serotype A-specific
      determinants are largely involved in the mechanisms of adherence of C. albicans A
      to human buccal epithelial cells.

PMID- 1375201
TI  - Effect of adenylate cyclase activators on C5a-induced human neutrophil
      aggregation, enzyme release and superoxide production.
AB  - The effect of adenylate cyclase activators on C5a- and f-Met-Leu-Phe-induced
      human neutrophil aggregation, enzyme release and superoxide production was
      investigated. C5a-stimulated superoxide production was markedly inhibited by
      adenylate cyclase activators, and the order of potency was PGE1 greater than
      isoproterenol greater than epinephrine greater than PGF2 alpha, which correlated
      with intracellular cAMP levels. However, neutrophil aggregation was inhibited by
      PGE1, PGE2, isoproterenol and epinephrine only at concentrations greater than 10(
      6) M. Lysozyme release was inhibited only via PGEs in the presence of the
      phosphodiesterase inhibitor, methylisobutylxanthine. These results suggest that
      in the human neutrophil: (1) C5a-induced superoxide production is more sensitive
      to regulation by cAMP than neutrophil aggregation or enzyme release, and (2) the
      type of receptor occupied as well as the threshold level of cAMP are important in
      the regulation of neutrophil aggregation and enzyme release stimulated by C5a.

PMID- 1375202
TI  - Antigenic differences between subsets of peripheral blood lymphocytes differing
      in their right angle light scatter in flow cytometric analysis.
AB  - The expression of various cell surface markers on peripheral blood lymphocytes
      (PBL) of young children and of adults was determined by flow cytometry among
      cells with either high or low light side scatter (SSC). In adults and in
      children, CD4+ lymphocytes (helper T cells) were more abundant among PBL with low
      SSC than among PBL with high SSC. The proportion of CD57+ (Leu-7+) cells (NK
      cells and a subset of CD8+ T cells) was significantly elevated among high SSC
      PBL, while that of CD8+ PBL (cytotoxic suppressor T cells) was only slightly
      elevated. CD4+ and CD8+ lymphocytes which coexpressed the CD29 marker,
      characteristic for activated or memory T cells, were significantly more abundant
      among lymphocytes with high SSC. In adults, the proportion of CD4+ CD45RA+
      lymphocytes, naive T cells, was significantly higher among low SSC cells. The
      present study indicates that determination of the SSC of lymphocyte subsets by
      flow cytometry can improve the discrimination among lymphocyte subpopulations and
      contribute to assessment of their state of activation.

PMID- 1375204
TI  - Effect of phospholipase A2 inhibitor ONO-RS-082 on substance P-induced histamine
      release from rat peritoneal mast cells.
AB  - Rat peritoneal mast cells purified on a Percoll gradient were challenged with
      substance P (SP) and the effect of phospholipase A2 inhibitor ONO-RS-082 on SP
      induced histamine release from the cells was investigated. 10(-5) mol/l SP caused
      a significant histamine release and the amount of histamine release reached
      maximum at 1 min after the challenge. ONO-RS-082 inhibited the SP-induced
      histamine release in a concentration-dependent manner at the concentration from
      10(-6) to 10(-4) mol/l, suggesting possible involvement of phospholipase A2 in SP
      induced histamine release from rat peritoneal mast cells.

PMID- 1375203
TI  - Comparison of the modulatory effect of ketotifen, sodium cromoglycate, procaterol
      and salbutamol in human skin, lung and tonsil mast cells.
AB  - To assess the influence of mast cell heterogeneity on the inhibition of mediator
      release by drugs, the effects of ketotifen, sodium cromoglycate and beta
      adrenoceptor agonists were examined against IgE-dependent histamine and
      prostaglandin D2 release from enzymatically dispersed human skin, lung and
      tonsillar mast cells. At high concentrations, ketotifen was an inhibitor of
      histamine and prostaglandin D2 release from lung and tonsillar mast cells. No
      cross-tachyphylaxis with sodium cromoglycate was seen. In skin mast cells no
      inhibition of mediator release was observed with 1.0 microM ketotifen, above
      which histamine release was induced. Sodium cromoglycate was a weak inhibitor of
      histamine and prostaglandin D2 release from lung and tonsillar mast cells and
      showed tachyphylaxis. Sodium cromoglycate did not inhibit histamine and
      prostaglandin D2 release from skin mast cells. On the other hand, no
      heterogeneity was observed with the beta-adrenoceptor agonists, procaterol and
      salbutamol. beta-Adrenoceptor stimulants were significantly more effective in
      inhibiting prostaglandin D2 than histamine release. No tachyphylaxis was seen
      with prolongation of the incubation time before challenge. Our results suggest
      that human mast cells are heterogeneous with respect to the modulation of
      mediator release by ketotifen and sodium cromoglycate but not beta-adrenoceptor
      agonists.

PMID- 1375205
TI  - Comparison of substance P-induced and compound 48/80-induced neutrophil
      infiltrations in mouse skin.
AB  - It has recently been shown that substance P induces neutrophil infiltration in
      the skin, which is mediated through mast cell degranulation. Since substance P
      activates both skin mast cells and vascular endothelial cells, we compared the
      potencies of substance P and a mast cell-degranulating agent, compound 48/80,
      which is inactive for vascular endothelial cells, in inducing neutrophil
      infiltration in mouse skin. We also examined the effect of the C-terminal peptide
      of substance P, SP6-11, which is active for vascular endothelial cells, on
      compound 48/80-induced neutrophil infiltration in the skin. Subcutaneous
      administrations of substance P (10(-7) to 10(-5) M; 0.1 ml) and compound 48/80
      (0.5-50 micrograms/ml) induced neutrophil infiltrations and mast cell
      degranulations in mouse skin in a concentration-dependent fashion. Moreover,
      substance P induced more neutrophil infiltrations than compound 48/80 in terms of
      the magnitude of mast cell degranulations. SP6-11 (10(-6) to 10(-4) M) induced no
      significant neutrophil infiltration or mast cell degranulation, but increased the
      vascular permeability of endothelial cells in the skin. Furthermore, SP6-11
      enhanced compound 48/80-induced neutrophil infiltration without any increase in
      mast cell degranulation. Our results indicate that, in addition to mast cell
      degranulation, the activation of vascular endothelial cells is involved in
      substance P-induced neutrophil infiltration in the skin.

PMID- 1375206
TI  - Permethrin versus crotamiton and lindane in the treatment of scabies.

PMID- 1375207
TI  - Morphological features of the myenteric plexus of the stomach of the axolotl,
      Ambystoma mexicanum, revealed by immunocytochemistry.
AB  - The general morphology of the intramural innervation of the myenteric plexus of
      the axolotl stomach has been investigated using antisera raised against neuron
      specific enolase and a microtubule-associated protein. Additionally, the
      occurrence of serotonin and several peptidergic neurotransmitter/neuromodulator
      substances was studied. Immunoreactivity for galanin, vasoactive intestinal
      polypeptide, substance P and neuromedin U was found in both fibres and intrinsic
      perikarya, whereas the serotonin and calcitonin gene-related peptide-like
      substance-containing nerve fibres seemed to be of extrinsic origin. The axolotl
      stomach myenteric plexus appeared to be devoid of enkephalin-, neuropeptide Y-,
      somatostatin- and bombesin-like immunoreactive nerve fibres and nerve cell
      bodies. Double labelling experiments revealed the presence of a subpopulation of
      substance P/calcitonin gene-related peptide-like immunoreactive nerve fibres.
      Contrary to mammals, no coexistence of neuromedin U and substance P was found.
      Our findings illustrate that besides a number of similarities, considerable
      species differences exist between urodeles and anurans with regard to the
      organization of the enteric nervous system.

PMID- 1375209
TI  - Dye standards, Part I: Terminology and general principles. European Committee for
      Clinical Laboratory Standards (ECCLS), Subcommittee on Reference Materials for
      Tissue Stains (SRMTS).

PMID- 1375208
TI  - Unfixed tissue for electron immunocytochemistry: a simple preparation method for
      colloidal gold localization of sensitive epitopes using ethanediol dehydration.
AB  - A quick, simple protocol is described for the preparation of tissue for electron
      immunocytochemistry without the use of fixatives or deleterious solvents. Fresh,
      normal human colon was rapidly dehydrated in ethanediol (ethylene glycol) then
      embedded directly in low-acid glycol methacrylate. Using both mono- and
      polyclonal antibodies, in conjunction with colloidal gold probes, a range of
      intra- and extracellular epitopes were localized; these epitopes included
      lysozyme, chromogranin, desmin and collagen IV. Overall, the tissue compared well
      with material fixed in glutaraldehyde, partially dehydrated and embedded in LR
      White acrylic resin. Ultrastructural detail was good and was further enhanced,
      without affecting probe density and epitope localization, by the addition of 1%
      tannic acid or 1% uranyl acetate to the dehydrant. The technique is applicable to
      a wide range of tissues, allowing excellent antigen retention which might prove
      useful for the immunolocalization of sensitive epitopes.

PMID- 1375210
TI  - Dye standards, Part II. 1: Pyronin Y (CI 45005). European Committee for Clinical
      Laboratory Standards (ECCLS), Subcommittee on Reference Materials for Tissue
      Stains (SRMTS).

PMID- 1375211
TI  - Dye standards, Part II. 2: Methyl green (CI 42585) and ethyl green (CI 42590).
      European Committee for Clinical Laboratory Standards (ECCLS), Subcommittee on
      Reference Materials for Tissue Stains (SRMTS).

PMID- 1375212
TI  - Dye standards, Part II. 3: Thionin (CI 52000). European Committee for Clinical
      Laboratory Standards (ECCLS), Subcommittee on Reference Materials for Tissue
      Stains (SRMTS).

PMID- 1375213
TI  - Dye standards, Part II. 4: Victoria blue B (CI 44045). European Committee for
      Clinical Laboratory Standards (ECCLS), Subcommittee on Reference Materials for
      Tissue Stains (SRMTS).

PMID- 1375214
TI  - Dye standards, Part II. 5: Pararosaniline (CI 42500). European Committee for
      Clinical Laboratory Standards (ECCLS), Subcommittee on Reference Materials for
      Tissue Stains (SRMTS).

PMID- 1375215
TI  - Dye standards, Part II. 6: Rosaniline (CI 42510). European Committee for Clinical
      Laboratory Standards (ECCLS), Subcommittee on Reference Materials for Tissue
      Stains (SRMTS).

PMID- 1375216
TI  - Dye standards, Part II. 7: Magenta II (no CI number). European Committee for
      Clinical Laboratory Standards (ECCLS), Subcommittee on Reference Materials for
      Tissue Stains (SRMTS).

PMID- 1375217
TI  - Dye standards, Part II. 8: New fuchsin (CI 42520). European Committee for
      Clinical Laboratory Standards (ECCLS), Subcommittee on Reference Materials for
      Tissue Stains (SRMTS).

PMID- 1375218
TI  - Stereotaxic radiosurgery for brain metastases: the importance of adjuvant whole
      brain irradiation.
AB  - Stereotaxic radiosurgery delivered from a modified 4 MV linear accelerator was
      used to treat 47 brain metastases in 27 patients at Stanford. Response was
      assessed in 41 lesions. Histopathologies included adenocarcinoma (24 lesions),
      renal cell carcinoma (9 lesions), melanoma (6 lesions), and squamous cell
      carcinoma (2 lesions). Follow-up ranged from 1.0-16.5 months, with a median of
      5.0 months. Radiographic local control was achieved in 88% of the lesions. Three
      patients developed enlarging contrast-enhancing lesions in the radiosurgical
      field; one of these was biopsied and revealed necrosis with no viable tumor.
      Adjuvant whole brain irradiation (10 patients) was associated with regional
      intracranial control in 80% of patients. This was statistically superior (p =
      0.0007) to the regional intracranial control rate achieved when radiosurgery
      alone was employed (6 patients). Most patients reported resolution of their
      neurologic symptoms, and were able to discontinue dexamethasone without
      impairment of neurologic function.

PMID- 1375219
TI  - Vanadate stimulates system A amino acid transport activity in skeletal muscle.
      Evidence for the involvement of intracellular pH as a mediator of vanadate
      action.
AB  - Sodium orthovanadate caused a 2-fold stimulation of system A transport activity
      in soleus muscle, as assessed by the uptake of the nonmetabolizable analog 2
      (methylamino)isobutyric acid (MeAIB). The effect of vanadate on system A was
      rapid, concentration-dependent and was characterized by an increased Vmax without
      modification of Km for MeAIB. Under these conditions, vanadate also activated 3-O
      methylglucose uptake and lactate production. The effects of vanadate on muscle
      metabolism showed a complex interaction with the effects of insulin. Thus, the
      stimulatory effects of vanadate and insulin on MeAIB and 3-O-methylglucose uptake
      were not additive; however, the effects of insulin and vanadate on lactate
      production were additive. In spite of the lack of additivity, insulin- and
      vanadate-induced stimulation of system A differed in their sensitivity to
      gramicidin D, being the vanadate effect more susceptible to inhibition by
      gramicidin D than the insulin effect. System A transport activity shows a
      dependence on pH, and recent results suggest the presence of critical histidine
      residues on the A carrier that may be responsible for its pH dependence (Bertran,
      J., Roca, A., Pola, E., Testar, X., Zorzano, A. & Palacin, M. (1991) J. Biol.
      Chem. 266, 798-802). In this regard, a rise in extracellular pH led to a
      substantial activation of system A. Furthermore, lowering of muscle intracellular
      pH induced by ethylisopropylamiloride (EIPA), a specific inhibitor of
      sodium/proton exchange activity, led to inhibition of system A. This suggests
      that critical histidine residues are present in an intracellular localization on
      the A carrier. Furthermore, the rate of muscle glycolysis was also altered in
      response to a rise in extracellular pH or to EIPA treatment. Regarding the
      mechanisms involved in vanadate action, vanadate treatment in the incubated
      soleus muscle did not cause any significant stimulation of tyrosine kinase
      activity after partial purification of muscle insulin receptors. On the other
      hand, vanadate but not insulin caused a substantial increase in muscle
      intracellular pH as assessed by 5,5'-dimethyloxazolidine-2,4-dione equilibrium.
      This effect of vanadate on intracellular pH was not due to activation of the
      sodium/proton exchanger, since it was not blocked by EIPA. Based on these
      findings, we suggest that alkalinization of muscle intracellular pH might mediate
      the effects of vanadate on system A and on glycolysis.

PMID- 1375220
TI  - Receptor-induced phosphorylation by mammary-derived growth factor 1 in mammary
      epithelial cell lines.
AB  - Previous work has shown that a mammary-derived growth factor (MDGF1), a human
      milk-derived, acidic, 62-kDa, N-glycosylated growth factor binds to cell surface
      receptors and stimulates proliferation of mammary epithelial cells. An 18-amino
      acid N-terminal partial sequence of the factor did not show any homology to other
      known growth factors or proteins. Using polyclonal antiserum raised against the
      synthetic peptide, we demonstrated that conditioned medium prepared from human
      breast cancer cell lines contains the factor. The antibody could adsorb the
      biological activity of the factor present in the conditioned medium. Earlier
      experiments on receptor cross-linking indicated that the receptor was
      approximately 120-140 kDa. Since tyrosine phosphorylation plays a crucial role in
      cell proliferation and cell transformation, experiments were conducted to find
      out whether MDGF1 induces the appearance of phosphotyrosine in MDGF1-receptor
      positive MDA-MB 468, MCF-7, and 184A1N4 cell lines compared to receptor-negative
      lines. Western blot analysis using monoclonal antiphosphotyrosine indicated that
      MDGF1 induces phosphotyrosine in a 180-185-kDa protein in MDGF1 receptor-positive
      cell lines. Phosphorylation was not blocked and phosphorylated proteins were not
      immunoprecipitated by an antibody directed against the binding site of the EGF
      receptor. Cell membrane fractionation demonstrated that phosphorylation induced
      by MDGF1 was membrane-associated. The nature of this 180-185-kDa protein and its
      possible relationship to the MDGF1 receptor are under investigation.

PMID- 1375221
TI  - Induction of expression of the cystic fibrosis transmembrane conductance
      regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) was studied in HT
      29 human colonic carcinoma cells with the aim of assessing possible mechanisms of
      up-regulation of its expression. CFTR was identified and quantified in total cell
      extracts by Western immunoblots using a monoclonal anti-CFTR antibody and was
      functionally assessed by tracer Cl-efflux from intact cells. It was found that
      various stimuli that lead to a sustained (greater than or equal to 8 h) elevation
      of intracellular cyclic AMP elicited a marked and specific increase in CFTR
      expression in cell membranes and concomitant activation of Cl- secretion. Further
      activation of Cl- secretion was obtained by additional short term activation by
      cyclic AMP analogues or cyclic AMP-inducing agents. Blockers of transcription or
      translation largely depressed the cAMP-mediated induction of CFTR levels and
      associated function, indicating that the inductive phenomenon was at the
      transcriptional level. The results imply the involvement of putative cyclic AMP
      responsive (and related) elements that are present in the CFTR gene promoter and
      that are known to modulate eukaryotic gene expression. Activation of these
      elements by various stimuli might provide pharmacological tools for up-regulation
      of CFTR expression at both biochemical and physiological levels.

PMID- 1375222
TI  - Molecular and immunological characterization of ADP-ribosylarginine hydrolases.
AB  - Mono-ADP-ribosylation is a reversible modification of proteins with NAD:arginine
      ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the forward
      and reverse reactions, respectively. Hydrolase activities were present in a
      variety of animal species, with the highest specific activities found in rat and
      mouse brain, spleen, and testis. Rat and mouse hydrolases were dithiothreitol-
      and Mg(2+)-dependent, whereas the bovine and guinea pig enzymes were
      dithiothreitol-independent. A rat brain hydrolase was purified approximately
      20,000-fold and represented the major approximately 39-kDa protein on denaturing
      gels. Immunoaffinity-purified rabbit polyclonal antibodies reacted with 39-kDa
      proteins from turkey erythrocytes and rat, mouse, and calf brains. A rat brain
      cDNA library was screened using oligonucleotide and polymerase chain reaction
      generated cDNA probes. Inserts from two overlapping clones yielded a composite
      sequence that included a 1086-base pair open reading frame, which contained amino
      acid sequences found in the purified hydrolase. A hydrolase fusion protein,
      synthesized in Escherichia coli, reacted with anti-39-kDa polyclonal antibodies
      and exhibited Mg(2+)- and dithiothreitol-dependent hydrolase activity. A coding
      region cDNA hybridized readily to a 1.7-kilobase band in rat and mouse poly(A)+
      RNA, but poorly to bovine, chicken, rabbit, and human poly(A)+ RNA. The
      immunological and molecular biological data are consistent with partial
      conservation of hydrolase structure across animal species.

PMID- 1375223
TI  - Dihydropyridine-sensitive L-type Ca2+ channels in human foreskin fibroblast
      cells. Characterization of activation with the growth factor Lys-bradykinin.
AB  - We have previously characterized the calcium response of cultured human
      fibroblasts (HSWP cells) to stimulation by the mitogen Lys-bradykinin (BK). We
      have reported a biphasic response which includes a rapid rise to a peak that
      appears to result from mobilization of internal calcium, and a plateau phase,
      which is due to influx of external calcium (Byron, K., Babnigg, G., Villereal, M.
      L. (1992) J. Biol. Chem. 267, 108-118). In this paper we examine participation of
      L-type voltage operated calcium channels in the calcium entry phase of BK
      stimulated HSWP cells. We show that there is an increase in 45Ca2+ uptake and an
      increase in intracellular free calcium concentration ([Ca2+]i) as measured by
      fura-2, when HSWP cells are stimulated with the L-channel agonist Bay K 8644
      under depolarizing conditions. Furthermore, both of these effects are inhibited
      by low doses of the dihydropyridine antagonist nitrendipine. We also report that
      BK stimulation of 45Ca2+ uptake can be significantly inhibited by low doses of
      nitrendipine, while nitrendipine treatment has no effect on the BK-induced rise
      in [Ca2+]i, as measured by fura-2. These results suggest that under normal
      conditions the portion of the BK-stimulated Ca2+ influx which is mediated by a
      nitrendipine-sensitive entry pathway is invisible to the fura-2 technique used to
      measure [Ca2+]i. This suggest that the nitrendipine-sensitive influx pathway
      admits calcium preferentially into an intracellular store that is isolated from
      fura-2. This idea is supported by the observation that in media where calcium has
      been replaced by 2 mM Ba2+ nitrendipine inhibits most of the BK-stimulated Ba2+
      influx.

PMID- 1375224
TI  - Tyrosine-phosphorylated epidermal growth factor receptor and cellular p130
      provide high affinity binding substrates to analyze Crk-phosphotyrosine-dependent
      interactions in vitro.
AB  - The genome of CT10 avian sarcoma virus encodes a 47-kDa fusion protein that
      consists of viral gag sequences fused to a cell-derived sequence containing SH2
      and SH3 domains (v-crk). Genetic and biochemical evidence suggests that v-Crk can
      induce transformation of chicken embryo fibroblasts by influencing the activity
      of cellular proteins involved in growth regulation. In this report, we have
      developed an in vitro microtiter assay to study the binding of bacterially
      expressed glutathione S-transferase-fusion proteins of v-Crk and its cellular
      homolog, c-Crk, to the phosphorylated epidermal growth factor receptor (EGFR).
      Competitive binding data are presented that compare the abilities of heterologous
      glutathione S-transferase-fusion proteins containing GAPSH2[N], AblSH2, SrcSH2,
      and PLC-gamma SH2[N] sequences to inhibit Crk binding. Results indicate that both
      full-length Crk and GAPSH2[N] bind the phosphorylated EGFR with high affinity and
      can quantitatively compete the binding of each other by competitive enzyme-linked
      immunosorbent assay. Binding of full-length Crk or the isolated SH2 domains of
      GAP or Abl resulted in a significant protection of phosphorylated EGFR against
      dephosphorylation by cellular phosphatase activity, but did not appear to
      stimulate the intrinsic tyrosine kinase activity of the EGFR. To extend these
      findings to p130, the major phosphotyrosine-containing protein in CT10
      transformed cells, we utilized a nitrocellulose filter binding assay. Results
      demonstrate high affinity binding of Crk toward denatured p130 and, as is the
      case for phosphorylated EGFR, Crk binding can partially protect p130 from
      phosphatase activity. However, no apparent competition of Crk binding was noted
      with heterologous SH2-containing proteins including GAPSH2[N], suggesting a
      possible specificity of Crk-p130 binding. These data are consistent with a direct
      role of SH2 in the modulation of cellular phosphotyrosine status in vivo.

PMID- 1375225
TI  - Isolation and expression of a gene encoding L-14-II, a new human soluble lactose
      binding lectin.
AB  - In the course of screening a human hepatoma cDNA library with antibody raised
      against a mammalian lectin with subunit molecular weight of about 14,000, we
      detected a partial cDNA encoding a related but distinct protein that was possibly
      a homologous lectin (Gitt and Barondes, 1986). We here report the isolation and
      sequencing of a full-length cDNA for this protein from a HepG2 cDNA library. The
      cDNA encodes a protein with subunit molecular weight of 14,650. Expression of the
      coding sequence in Escherichia coli yields a product that binds to a lactose
      affinity column and is specifically eluted with lactose, confirming that this new
      protein is a lectin. Like its well studied relative, here called L-14-I, the new
      lectin, L-14-II, exists as a homodimer in solution. The two related human lectins
      have 43% amino acid sequence identity. The genomic DNA encoding L-14-II (LGALS2)
      contains four exons with similar intron placement to L-14-I (LGALS1); but the
      genomic upstream region, which contains several sequences characteristic of
      regulatory elements, differs significantly from L-14-I.

PMID- 1375226
TI  - Erythropoietin induces the tyrosine phosphorylation of its own receptor in human
      erythropoietin-responsive cells.
AB  - Using the human erythropoietin-responsive hematopoietic cell line UT-7, we showed
      that erythropoietin (Epo) rapidly and specifically induced the tyrosine
      phosphorylation of its own receptor (M(r) 75,000) and increased the tyrosine
      phosphorylation of other proteins of M(r) 140,000, 120,000, 95,000, 60,000,
      57,000, and 42,000. Neither granulocyte-macrophage colony-stimulating factor,
      interleukin 3, interleukin 6, nor the kit ligand induced the phosphorylation of
      the M(r) 75,000 receptor protein, although these growth factors induced the
      phosphorylation of other proteins. Cross-linking experiments using 125I-Epo
      indicated that the UT-7 cells expressed three Epo receptor subunits, of M(r)
      100,000, 85,000, and 75,000, among which only the M(r) 75,000 subunit was
      tyrosine-phosphorylated following activation with Epo.

PMID- 1375227
TI  - Functional analysis of the mouse alpha-fetoprotein enhancers and their
      subfragments in primary mouse hepatocyte cultures.
AB  - We have compared the activities of mouse alpha-fetoprotein (AFP) enhancers I, II,
      and III with their minimal enhancer fragments (Mers) I, II, and III and with the
      entire 7-kilobase pair enhancer domain by transient expression assay in primary
      fetal mouse liver cells. The level of expression directed by the AFP promoter [p(
      1009)AFPcat] alone is stimulated at least 10-fold by the entire AFP enhancer
      domain (-1009 to -6983). Enhancer I can drive the level of chloramphenicol
      acetyltransferase activity equivalent to that of the entire enhancer domain,
      whereas the increase in activity by enhancers II and III is significantly lower
      (1.5-fold). MersI, II, and III all mediate a greater increase in activity than
      their corresponding enhancer regions. The increase with MerI is 16-fold. Using
      DNase I protection analyses we identified 3 protein-binding regions in MerI; site
      Ia binds liver and brain nuclear proteins; site Ib binds liver, kidney, and brain
      nuclear proteins as well as purified C/EBP; site Ic binds liver and kidney
      nuclear proteins. Site-specific mutation of Ia, Ib, or Ic showed a 10-25%
      reduction in chloramphenicol acetyltransferase expression; deletion of the C/EBP
      binding site in Ib showed a 45% reduction in activity and mutation of all 3 sites
      (Ia, Ib, and Ic) resulted in a 75% reduction in activity. Our studies indicate no
      single trans-acting factor is absolutely essential for enhancer activity, and
      that the enhancer activity of MerI is mediated via a combinatorial and additive
      mechanism.

PMID- 1375228
TI  - Purification and molecular cloning of the APO-1 cell surface antigen, a member of
      the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence
      identity with the Fas antigen.
AB  - The APO-1 antigen as defined by the mouse monoclonal antibody anti-APO-1 was
      previously found to be expressed on the cell surface of activated human T and B
      lymphocytes and a variety of malignant human lymphoid cell lines. Cross-linking
      of the APO-1 antigen by anti-APO-1 induced programmed cell death, apoptosis, of
      APO-1 positive cells. To characterize the APO-1 cell surface molecule and to
      better understand its role in induction of apoptosis, the APO-1 protein was
      purified to homogeneity from membranes of SKW6.4 B lymphoblastoid cells by
      solubilization with sodium deoxycholate, affinity chromatography with anti-APO-1
      antibody, and reversed phase high performance liquid chromatography. Each
      purification step was followed by an APO-1-specific solid phase enzyme-linked
      immunosorbent assay using the monoclonal antibody anti-APO-1. In sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, the APO-1 antigen was found to be a
      membrane glycoprotein of 48-kDa. Endoproteinase-cleaved peptides of the APO-1
      protein were subjected to amino acid sequencing, and corresponding
      oligonucleotides were used to identify a full-length APO-1 cDNA clone from an
      SKW6.4 cDNA library. The deduced amino acid sequence of APO-1 showed sequence
      identity with the Fas antigen, a cysteine-rich transmembrane protein of 335 amino
      acids with significant similarity to the members of the tumor necrosis
      factor/nerve growth factor receptor superfamily. The APO-1 antigen was expressed
      upon transfection of APO-1 cDNA into BL60-P7 Burkitt's lymphoma cells and
      conferred sensitivity towards anti-APO-1-induced apoptosis to the transfectants.

PMID- 1375229
TI  - Mechanism of interferon action. cDNA structure and regulation of a novel splice
      site variant of the catalytic subunit of human protein kinase A from interferon
      treated human cells.
AB  - A molecular cDNA clone (KIN27) was isolated that encodes a novel variant of the
      catalytic subunit C alpha of the human cyclic AMP-dependent protein kinase (PKA).
      Analysis of PKA genomic sequence data revealed that the KIN27 variant transcripts
      likely result from alternative splice-site selection of the C alpha gene
      transcripts. The KIN27 cDNA has therefore been designated C alpha 2. RNA
      amplification by polymerase chain reaction revealed that KIN27 C alpha 2 splice
      site variant RNA and PKA C alpha RNA were both expressed in the amnion U and HeLa
      human cell lines. C alpha RNA was about 3- to 5-fold more abundant than C alpha 2
      RNA. Interferon treatment decreased the steady-state amount of the C alpha 2 RNA
      relative to C alpha RNA. These results suggest that alternative splicing may
      contribute to the structural heterogeneity of C subunits expressed in human cells
      and that interferon may affect this process.

PMID- 1375230
TI  - Cytosolic double-stranded RNA-dependent protein kinase is likely a dimer of
      partially phosphorylated Mr = 66,000 subunits.
AB  - The work described in this report suggests the existence of two biochemically
      distinguishable forms of the interferon-inducible, double-stranded RNA-dependent
      protein kinase. Kinase isolated from the cytosolic fraction (S-100) and the
      ribosome salt wash fraction of interferon-treated cells differed in their
      chromatographic properties. S-100 kinase eluted from a gel filtration column with
      M(r) = 140,000-160,000 and was predominantly anionic in nature, whereas ribosomal
      kinase eluted with M(r) = 66,000 and was predominantly cationic in nature.
      Purified preparations of S-100 kinase contained the M(r) = 66,000 subunit, P1, as
      the only polypeptide present in stoichiometric amounts, and thus the S-100 kinase
      appears to be a dimer of P1 subunits. Dimerization of the S-100 kinase was
      dependent on the phosphorylation state of the enzyme. Kinase isolated from S-100
      was partially phosphorylated. Dephosphorylation of the S-100 kinase by treatment
      with alkaline phosphatase resulted in a monomeric form of the enzyme with
      biochemical characteristics similar to that of the ribosome salt wash kinase.

PMID- 1375231
TI  - The juvenile microtubule-associated protein MAP2c is a rod-like molecule that
      forms antiparallel dimers.
AB  - We have developed a procedure to isolate the microtubule-associated protein 2c
      (MAP2c), a juvenile form of MAP2 occurring in mammalian brain. The shape, size,
      self-association, and antibody interactions of MAP2c were studied. Monomeric
      MAP2c is an elongated molecule with a length approximately 48 nm, considerably
      shorter than the higher molecular weight forms MAP2a or b of adult brain. Two
      monoclonal antibodies whose epitopes are near the N or C terminus, respectively,
      are located close to the opposite ends of the MAP2c rods. This places constraints
      on the types of internal folding of the molecule. MAP2c self-associates into
      dimers and fibrous aggregates. The dimers are predominantly antiparallel and
      nearly in register, as judged by antibody labeling.

PMID- 1375232
TI  - A recombinant ectodomain of the receptor for the stem cell factor (SCF) retains
      ligand-induced receptor dimerization and antagonizes SCF-stimulated cellular
      responses.
AB  - The stem cell factor (SCF) is a polypeptide ligand that is essential for the
      development of germ cells, hematopoietic progenitor cells, and melanocyte
      precursors. It binds to a tyrosine kinase membrane receptor that is encoded by
      the c-kit proto-oncogene. We have constructed an expression vector that directs
      the synthesis of the entire extracellular ligand-binding domain of the Kit/SCF
      receptor. When expressed and amplified in Chinese hamster ovary cells, a secreted
      90-kDa glycoprotein could be harvested from the growth medium of the cells in a
      soluble form. This extracellular portion of the Kit/SCF receptor, denoted Kit-X,
      was recognized by antibodies specific to the SCF receptor; and when injected into
      animals, it raised antibodies that were reactive with the complete membrane form
      of the receptor. Direct binding and covalent cross-linking of radiolabeled SCF
      showed that Kit-X fully retained high affinity ligand binding and also underwent
      efficient dimerization in the presence of the ligand. The capacity of Kit-X to
      act as an antagonist of SCF was assayed on cultured cells that overexpress the
      receptor. Simultaneous addition of SCF and Kit-X to these cells resulted in a
      stoichiometric inhibition of SCF binding and a consequent decrease in
      autophosphorylation of the SCF receptor on tyrosine residues. The inhibition
      extended to later SCF-mediated responses, including the association of the
      receptor with phosphatidylinositol 3'-kinase and coupling to the Raf1 protein
      kinase. These results indicate that the recombinant ectodomain of the Kit-SCF
      receptor can be used as a specific antagonist of SCF actions and may enable
      detailed molecular analysis of ligand-receptor interactions.

PMID- 1375233
TI  - Comparison of HIV-1 and avian myeloblastosis virus reverse transcriptase fidelity
      on RNA and DNA templates.
AB  - A comparison of the fidelity of reverse transcriptases (RT) from human
      immunodeficiency virus (HIV-1) and avian myeloblastosis virus (AMV) is made using
      RNA and DNA primer-template molecules in vitro. Selected template target sites
      containing either uracil or thymine are used to measure nucleotide insertion
      fidelities and to compare the efficiency of extending mismatched nucleotides at
      primer 3'-termini. HIV-1 reverse transcriptase is observed to incorporate as many
      as three consecutive mismatches and to continue efficient elongation from
      mismatched primer 3'-termini without discernible pausing. Nucleotide misinsertion
      and mispair extension efficiencies are similar for both enzymes on RNA and DNA
      templates having identical surrounding sequence. HIV-1 and AMV reverse
      transcriptases form G.T and G.U mismatches most efficiently, between 1.6 x 10(-4)
      and 7 x 10(-4), and both enzymes extend G.U with exceptionally high efficiencies,
      2.7 x 10(-2) for HIV-1 RT and 4.5 x 10(-2) for AMV RT. Extension of the G.T
      mismatch is similar for AMV RT (5.8 x 10(-2) but 20-fold less efficient for HIV-1
      RT. C.U and C.T mismatches are formed by both enzymes in a frequency range of 4.4
      x 10(-5)-2.4 x 10(-4). HIV-1 RT extends these mismatches with slightly higher
      efficiencies (5.5 x 10(-3)-5.9 x 10(-3)) than AMV RT (5.6 x 10(-4)-2.1 x 10(-3)).
      Insertion of dTMP opposite U and T occur at about 1 x 10(-4)-2 x 10(-4) for HIV-1
      RT. For AMV RT, formation of T.U mispairs occurs with an 8-fold lower efficiency,
      whereas insertion of dTMP opposite T is not detected. This particular DNA
      template sequence generates a pause site for AMV RT but not HIV-1 RT. HIV-1 RT
      dissociation rate constants are about 8-fold larger from a DNA primer bound to a
      DNA template (0.5 s-1), as compared with an RNA template (0.06 s-1) at one site,
      and are at most 2-fold larger at another site. The equilibrium binding constant
      for HIV-1 RT bound to DNA primed RNA and DNA templates appears to be similar, KD
      approximately 2.5 nM. Values of kpol from 0.3 to 1.5 nucleotides/s are obtained
      for HIV-1 RT at the RNA and DNA template sites used to measure insertion and
      extension fidelity. The relatively high efficiency of mispair extension catalyzed
      by reverse transcriptases with both RNA and DNA templates suggests that a
      significant component of retroviral genetic variability may be related to the
      ability of reverse transcriptases to continue efficient synthesis of DNA
      containing mismatches on both RNA and DNA templates.

PMID- 1375234
TI  - Structure, distribution and composition of the extracellular matrix of human
      oocytes and cumulus masses.
AB  - The structure, distribution and composition of the extracellular matrix present
      around the human oocyte and in the cumulus was examined following fixation in the
      presence of ruthenium red. An extracellular matrix comprising granules and
      filaments is present in the cumulus layer, in the corona radiata, in the outer
      pores of the zona pellucida and in the perivitelline space surrounding
      unfertilized oocytes. In replicate samples, the extracellular matrix comprised
      filaments which were mostly very long, occasionally cross-connected by shorter
      filaments, and usually decorated with numerous small granules. Enzymatic
      digestion with affinity-purified trypsin or Streptomyces hyaluronidase removes
      the granules and filaments, respectively, at all levels of the oocyte-cumulus
      complex. These results are interpreted to mean that protein and hyaluronic acid
      are present in all extracellular compartments of the human oocyte-cumulus
      complex. The significance of this distribution of hyaluronic acid with respect to
      the role of sperm hyaluronidase in fertilization is discussed.

PMID- 1375235
TI  - Laboratory workup of microbial keratitis.
AB  - Accurate diagnosis is the key to proper management of microbial keratitis.
      Haphazard therapy for keratitis often results in frustration for both the doctor
      and the patient. Unsuccessful therapy allows the condition to linger on, and may
      provide the opportunity for more serious corneal complications to occur. In
      office cytological and gram stain smears along with laboratory cultures,
      sensitivities, and endotoxin testing are essential in developing an accurate
      initial diagnosis and successful treatment plan for microbial keratitis.

PMID- 1375236
TI  - Immunohistochemical and enzymehistochemical studies of peptidergic, aminergic and
      cholinergic innervation of the lacrimal gland of the monkey (Macaca fuscata).
AB  - The distribution of nerve fibers containing peptides which include calcitonin
      gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY) and
      vasoactive intestinal polypeptide (VIP) and enzymes of tyrosine hydroxylase (TH)
      and acetylcholinesterase (AchE) in the lacrimal gland of the monkey (Macaca
      fuscata) was studied using immunohistochemical and enzymehistochemical methods.
      We also examined the trigeminal ganglion (TG) and superior cervical ganglion
      (SCG) using the same methods. All peptide- and enzyme-containing nerve fibers
      examined in this study were present in the lacrimal gland and a consistent
      distribution pattern for each substance was found. CGRP-immunoreactive (IR) nerve
      fibers were mainly distributed around the blood vessels in the interlobular
      connective tissue. The distribution pattern of SP-IR nerve fibers was similar to
      that of CGRP-IR nerve fibers, but they were much less in number. NPY-IR nerve
      fibers were observed mostly around the blood vessels and occasionally in the
      interstitial stroma between the acini. Numerous VIP-IR nerve fibers were found
      surrounding the acini, ducts and blood vessels. TH-IR nerve fibers were also been
      around the blood vessels and in the interstitial stroma between the acini, as
      were NPY-IR fibers. The highest concentration of acetylcholinesterase (AchE)
      positive nerve fibers was present in the acini, ducts and blood vessels, showing
      a similar distribution to VIP-IR fibers. In the TG, 50% of medium and 30% of
      small ganglion cells were CGRP-IR cells, while 20% of medium and 25% of small
      ganglion cells were of the SP-IR types.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375237
TI  - Effects of nerve growth factor on cyclocytidine-induced growth responses of
      sympathectomized parotid or parotid of partially desalivated rat.
AB  - Cyclocytidine (CC), a potent antitumor agent, caused a 2.4- to 3.9-fold increase
      in [3H]thymidine uptake of rat parotid gland after 3 days of daily administration
      of the CC in a dose of 500 mg/kg body weight. Gland weight also was increased.
      Ablation of the submandibular-sublingual glands prior to initiation of the CC
      regimen prevented the usual CC-induced increase in [3H]thymidine uptake but this
      inhibition was partially reversed when nerve growth factor (NGF) was administered
      with the CC; values for [3H]thymidine uptake into parotid DNA were 81, 54, and
      73% of those of glands of intact CC-treated rats. Submandibular gland ablation
      did not prevent the usual CC-induced increase in parotid size, and administration
      of NGF had no effect. Sympathectomy of the salivary glands also inhibited the
      thymidine increase in parotid gland usually induced by CC but in addition it also
      inhibited the usual CC-induced increase in gland weight. NGF, however, failed to
      reverse the effects of sympathectomy on [3H]thymidine uptake or gland size: both
      remained at the same level observed in sympathectomized parotid not given NGF.

PMID- 1375238
TI  - Unknown dysmorphic syndromes and development delay in Saudi Arabia.
AB  - Forty-four Saudi Arabian patients with unknown dysmorphic syndromes were studied
      with respect to their level of cognitive delay. The relationship between such
      delay and particular patterns of dysmorphic features, as well as various
      demographic and historical data, were also investigated. Prognostication and
      genetic counseling are difficult for this group because little is known about
      morbidity or other factors. These concerns, along with broader issues, stimulated
      this study. Significant associations were found between level of cognitive
      function and consanguinity, abnormal motor and language milestones, and abnormal
      electroencephalograms. No significant relationship was found between various
      dysmorphic feature clusters and measured cognition. Concerns were expressed about
      demands on family and community for these children, as well as possible larger
      issues in this heavily consanguineous society. Further research, including
      epidemiologic studies, was recommended.

PMID- 1375239
TI  - Characterization of a monoclonal antibody that specifically binds to choline
      phospholipids and its use in immunocytochemistry.
AB  - A monoclonal IgM (MC22-33F), raised in response to mouse embryonic dental papilla
      cells, was selected for further analysis on the basis of the unusual resistance
      of its epitope to detergent extractions and protease treatments of cell cultures.
      Binding of MC22-33F to cultured cells was abolished after either pre-treatment of
      the cells with phospholypase C or pre-incubation of the hybridoma culture
      supernatant with multilamellar phosphatidylcholine-containing vesicles. MC22-33F
      reacted with phosphatidylcholine, with the phosphatidylcholine analogue
      dimethylphosphatidylethanolamine, and with sphingomyelin immobilized on
      polystyrene surfaces or in thin-layer chromatograms. Crossreaction with other
      phospholipids was not observed. The surface of cultured epithelial cells was
      labeled by MC22-33F at sites of bleb formation. Combining immunostaining by MC22
      33F and histochemical staining of cultured cells revealed codistribution of
      phospholipid-containing inclusions with either lysosomes or neutral fat droplets,
      and inhibition of lipid degradation by kanamycin resulted in a parallel
      accumulation of these inclusions and of neutral fats in the cytoplasm.
      Immunolabeling by MC22-33F of frozen mouse tissues was maximal in fat-storing and
      steroid-producing cells. Extracellular phospholipids present in calcifying
      cartilage septa strongly reacted with MC22-33F. This monoclonal antibody offers
      an interesting alternative to histochemical lipid stains for investigating fatty
      metamorphosis and extracellular lipid deposition under physiological and
      pathological conditions.

PMID- 1375240
TI  - The use of silver-enhanced 1-nm gold probes for light and electron microscopic
      localization of intra- and extracellular antigens in skin.
AB  - We used colloidal gold (1-nm diameter) with silver enhancement, in conjunction
      with a low-temperature post-embedding immunolabeling technique, to localize
      several antigens in normal skin at both the light and the electron microscopic
      level within the same tissue blocks. Normal skin subjected to cyrofixation and
      cryosubstitution and embedded in Lowicryl K11M was used as a substrate. Semi-thin
      sections (1 micron) were incubated in primary antibody (against epidermal
      basement membrane zone associated antigens and two keratin sub-types),
      biotinylated secondary antibodies, and then in 1-nm gold-conjugated streptavidin.
      Finally, the 1-nm gold label was enhanced using silver staining. Labeling of both
      basement membrane and keratin antigens was well demonstrated, and the area in the
      semi-thin sections showing the best structural preservation and the greatest
      intensity of immunolabeling was used to identify the part of the block to be used
      for ultra-thin sectioning. Ultra-thin sections were treated using a similar
      procedure to that employed for semi-thin sections. The labeling with silver
      enhanced 1-nm gold probes was intense and readily visible by electron microscopy,
      even at low magnification. We have found this technique to have a high degree of
      specificity and sensitivity for labeling both intra- and extracellular antigens
      in skin, with the added advantage of providing the means for studies at both
      light microscopic and electron microscopic level.

PMID- 1375241
TI  - Cultured human follicular dendritic cells. Growth characteristics and
      interactions with B lymphocytes.
AB  - Minced human tonsils were digested with DNase and collagenase, and lymphoid cell
      depleted low density cells were cultured and grown in granulocyte-macrophage-CSF.
      Large, morphologically homogenous adherent cells with elongated extensions grew
      continuously in culture. These nonphagocytic cells appear to be related to
      follicular dendritic cell (FDC) as they do not have properties of monocytic
      lineage cells or dendritic cells and because, like FDC, 1) they express CD11b,
      CD14, CD29, CD40, CD54, CD73, CD74, and VCAM-1, and do not express CD11c, CD22, T
      cell markers, CD18, CD25 and CD45; and 2) they bind human B lymphocytes and B
      cell lines, but not T lymphocytes by an adhesion blocked in part by mAb to VLA-4
      (CD49d). The cultured FDC also augmented B cell proliferation stimulated by anti
      mu sera and/or CD40 mAb. Cultured FDC spontaneously produced low levels of IL-6,
      but did not produce IL-1 alpha or TNF-alpha; however, after treatment with either
      IFN-gamma or LPS, they produced more IL-6. The expression of CD54 (ICAM-1) was
      elevated by treating the cultured FDC with either TNF-alpha, IL-1 beta, IFN-gamma
      or granulocyte-macrophage-CSF; in contrast, IL-4 had no effect on CD54 but rather
      up-regulated expression of VCAM-1. IFN-gamma, unlike the other cytokines tested,
      increased expression of a set of markers on cultured FDC (CD54, VCAM-1, and CD14)
      and converted these class II-negative cells into class II+ cells. The fact that
      various T cell-derived cytokines have different effects on FDC suggests that the
      T cell products may influence the manner by which FDC stimulate B cell
      proliferation and maturation.

PMID- 1375242
TI  - Preferential use of a T cell receptor V beta gene by acetylcholine receptor
      reactive T cells from myasthenia gravis-susceptible mice.
AB  - Experimental autoimmune myasthenia gravis (EAMG) is an important model for
      testing current concepts in autoimmunity and novel immunotherapies for autoimmune
      diseases. The EAMG autoantigen, acethylcholine receptor (AChR), is structurally
      and immunologically complex, a potential obstacle to the application of
      therapeutic strategies aimed at oligoclonal T cell populations. Inasmuch as we
      had previously shown that the clonal heterogeneity of T cell epitope recognition
      in EAMG was unexpectedly limited, we examined TCR V beta expression. AChR primed
      lymph node T cells and established AChR reactive T cell clones from EAMG
      susceptible C57BL/6 (B6; H-2b, Mls-1b) mice showed preferential utilization of
      the TCR V beta 6 segment of the TCR. After in vivo priming and in vitro
      restimulation for 7 days with AChR or a synthetic peptide bearing an
      immunodominant epitope, V beta 6 expressing lymph node cells (LNC) were expanded
      several-fold, accounting for up to 75% of recovered viable CD4+ cells. The LNC of
      B6.C-H-2bm12 (bm12; H-2bm12, Mls-1b) mice, which proliferated in response to AChR
      but not to the B6 immunodominant peptide, failed to expand V beta 6+ cells.
      Inasmuch as nonimmune bm12 and B6 animals had similar numbers of V beta 6+ LNC (4
      5%), this suggested that structural requirements for TCR recognition of Ag/MHC
      complexes dictated V beta usage. Results concerning peptide reactivity and V beta
      6 expression among T cells from (B6 x bm12)F1 animals also suggested that
      structure-function relationships, rather than negative selection or tolerance,
      accounted for the strain differences between B6 and bm12. To examine the
      potential effects of thymic negative selection of V beta 6+ cells on the T cell
      response to AChR, CB6F1 (H-2bxd, Mls-1b; V beta 6-expressing) and B6D2F1 (H-2bxd,
      Mls-1axb; V beta 6-deleting) strains were analyzed for AChR and peptide
      reactivity and V beta 6 expression. Both F1 strains responded well to AChR but
      the response of B6D2F1 mice to peptide was significantly reduced compared to
      CB6F1. Short and long term cultures of peptide-reactive B6D2F1 LNC showed no
      expansion of residual V beta 6+ cells, although similar cultures of CB6F1 LNC
      were composed of more than 60% V beta 6+ cells. The results from the F1 strains
      further indicated that the T cell repertoire for peptide was highly constrained
      and that non-V beta 6 expressing cells could only partially overcome Mls-mediated
      negative selection of V beta 6+ TCR capable of recognizing peptide.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1375243
TI  - Induction of isotype switching and Ig production by CD5+ and CD10+ human fetal B
      cells.
AB  - In the present study the capacity of early fetal B cells to produce Ig was
      investigated. It is shown that B cells from fetal liver, spleen, and bone marrow
      (BM) can be induced to produce IgM, IgG, IgG4, and IgE, but not IgA, in response
      to IL-4 in the presence of anti-CD40 mAb or cloned CD4+ T cells. Even splenic B
      cells from a human fetus of only 12 wk of gestation produced these Ig isotypes.
      IFN-alpha, IFN-gamma, and transforming growth factor-beta inhibited IL-4-induced
      IgE production in fetal B cells, as described for mature B cells. The majority of
      B cells in fetal spleen expressed CD5 and CD10 and greater than 99% of B cells in
      fetal BM were CD10+. Highly purified CD10+, CD19+ immature B cells and CD5+,
      CD19+ B cells could be induced to produce Ig, including IgG4 and IgE, in similar
      amounts as unseparated CD19+ B cells. Virtually all CD19+ cells still expressed
      CD10 after 12 days of culture. However, the IgE-producing cells at the end of the
      culture period were found in the CD19-,CD10- cell population, suggesting
      differentiation of CD19+,CD10+ B cells into CD19-,CD10- plasma cells. Pre-B cells
      are characterized by their lack of expression of surface IgM (sIgM). Only 30 to
      40% of BM B cells expressed sIgM. However, in contrast to sIgM+,CD10+,CD19+
      immature B cells, sorted sIgM-,CD10+,CD19+ pre-B cells failed to differentiate
      into Ig-secreting cells under the present culture conditions. Addition of IL-6 to
      these cultures was ineffective. Taken together, these results indicate that fetal
      CD5+ and CD10+ B cells are mature in their capacity to be induced to Ig isotype
      switching in vitro as soon as they express sIgM.

PMID- 1375244
TI  - Stimulation of mouse connective tissue-type mast cells by hemopoietic stem cell
      factor, a ligand for the c-kit receptor.
AB  - The proliferative capacity of mouse connective tissue-type mast cells (CTMC) was
      analyzed by using a newly discovered c-kit ligand, termed stem cell factor (SCF).
      More than 90% of CTMC in the peritoneal cavity responded to recombinant rat SCF
      (rrSCF) and were able to give rise to pure mast cell colonies in methylcellulose
      culture. Serial observation (mapping) of growth of individual CTMC in culture
      containing rrSCF confirmed their striking proliferative ability. No serum but
      accessory cells (non-CTMC cells) in the peritoneal population were required for
      the clonal growth of CTMC induced by rrSCF in our methylcellulose culture of
      whole peritoneal cells. The rrSCF-induced mast cell colony formation from
      peritoneal CTMC was completely inhibited by the addition of anti-c-kit antibody,
      which can block the binding of SCF to c-kit, to the culture. When IL-3 was
      combined with rrSCF, mast cell colonies dramatically increased in size. Mapping
      studies revealed that the combination of the two factors augmented the
      proliferative rate of CTMC. Approximately 60% of the constituent cells of the
      mast cell colonies which were formed from peritoneal CTMC in the culture
      containing rrSCF alone were stained with berberine sulfate, which is a
      characteristic of CTMC. However, most mast cells which were induced by rrSCF+IL-3
      from peritoneal CTMC contained berberine(-)-safranin(-)-Alcian blue(+) granules.
      Although IL-4 exhibited little synergism with rrSCF in the induction of CTMC
      proliferation, the addition of IL-4 to the culture containing rrSCF+IL-3 resulted
      in an increase in mast cells which retained CTMC characteristics.

PMID- 1375245
TI  - Monoclonal antibody detection of a major self peptide. MHC class II complex.
AB  - MHC class I and class II molecules transport foreign and self peptides to the
      cell surface and present them to T lymphocytes. Detection of these peptide:MHC
      complexes has thus far been limited to analysis of the response of a T cell.
      Previously, we showed that a mAb, Y-Ae, reacts with 10 to 15% of class II
      molecules on peripheral B lymphocytes and on cells in the thymus medulla but not
      thymus cortex in mice that express both I-Ab and I-Eb molecules. Elsewhere, we
      show that Y-Ae detects a self E alpha peptide bound to I-Ab molecules. Data
      presented here suggest that the antibody binds over the peptide binding groove of
      class II molecules, and, like a TCR, appears to recognize both the self peptide
      and polymorphic class II residues. In addition to B lymphocytes, the Y-Ae
      determinant is expressed at comparable levels on other APC, including macrophages
      and dendritic cells. Finally, the antibody does not react with invariant chain
      associated class II complexes, thus providing direct evidence that invariant
      chain:class II complexes and peptide:class II complexes are mutually exclusive.
      These data provide further evidence that immunologic self is of limited
      complexity, and have important implications for T cell selection, self tolerance,
      and autoreactivity.

PMID- 1375246
TI  - Substance P enhances IL-2 expression in activated human T cells.
AB  - Jurkat and HUT 78 T cell lines, as well as peripheral blood human T cells
      activated with PHA plus PMA were used to investigate the capacity of substance P
      (SP) neuropeptide to regulate IL-2 production. By using Northern blot analysis
      and dosage of the IL-2 release in cell supernatants, we show that SP can act as
      cosignal with PHA + PMA to enhance the expression of specific IL-2 mRNA and IL-2
      secretion in T cells. By using the N-terminal SP(1-4) or the C-terminal SP(4-11)
      fragments of the entire molecule, we show that the cosignal activity is carried
      by the C-terminal portion of SP. The SP and SP(4-11) optimal effects were
      observed at 10(-12) M and 10(-10) M when a broad range of concentrations from 10(
      6) M to 10(-13) M was tested. The increase of IL-2 mRNA obtained with 10(-12) M
      of SP in the activated Jurkat cells was reduced by adding 10(-10) or 10(-9) M of
      the SP antagonist (D-Pro2,-D-Phe7,-D-Trp9)SP to the culture, indicating the
      specificity of SP action. The up-regulation observed when 10(-12) M of SP was
      applied together with the mitogens on Jurkat cells, persisted after a 16-h
      culture period, time at which the IL-2 mRNA signal is normally back to a minimum
      level when the mitogens are used alone. Furthermore, an induction of IL-2 mRNA
      accumulation, in a 2-h pulse, was obtained with 10(-12) M of SP on Jurkat cells
      previously activated with mitogens for 16 h.

PMID- 1375247
TI  - Control of lipopolysaccharide (LPS) binding and LPS-induced tumor necrosis factor
      secretion in human peripheral blood monocytes.
AB  - We used flow cytometry to determine how LPS-binding protein (LBP) effects the
      binding of fluorescein-labeled LPS to human monocytes via receptor-dependent
      mechanisms. The addition of human, rabbit, mouse, or FCS strikingly increased the
      binding of LPS to monocytes compared with controls incubated in serum-free
      medium. This binding was totally prevented by preincubation of monocytes with
      MY4, an anti-CD14 mAb, or by enzymatic removal of CD14 from monocytes. Depletion
      of LBP from rabbit serum with anti-LBP antibodies also produced a similar
      suppression. Solutions of albumin did not support the enhanced binding observed
      in serum but the addition of purified rabbit LBP to albumin solutions resulted in
      binding similar to that observed in serum-containing medium. When type-specific
      anti-LPS mAb was added to human serum, LPS binding to monocytes occurred but was
      only partly inhibited by anti-CD14 mAb, suggesting that receptors other than CD14
      (presumably Fc or complement receptors) were involved. Serum increased by 100- to
      1000-fold the sensitivity of monocytes to the triggering by LPS resulting in TNF
      secretion. TNF secretion was inhibited by anti-CD14 mAb up to 100 ng/ml of LPS
      and by anti-LPS mAb up to 1 to 10 ng/ml. The inhibition of TNF secretion by anti
      LPS mAb appeared to be the result of directing LPS to monocyte receptors other
      than CD14. In contrast, in medium containing normal as well as acute serum and in
      the absence of anti-LPS antibodies, the binding of LPS to monocytes and the
      triggering of TNF secretion appeared to be mediated mainly by interactions
      between CD14 and LBP-LPS complexes.

PMID- 1375249
TI  - The effect of pepsin digestion in relation to the pre-S region on hepatitis B
      surface antigen-induced hypersensitivity.
AB  - The role of the pre-S region of the hepatitis B surface Ag (HBsAg) particle in
      hypersensitivity to HBsAg was evaluated in mice. Plasma-derived or recombinant
      HBsAg was digested with pepsin to prepare different forms of HBsAg with or
      without pre-S region. Strains of mice including AKR/J (H-2k), A.SW (H-2s), C3H/He
      (H-2k), and CBA/J (H-2k) did not respond to the major S protein with regard to
      hypersensitivity. However, the pre-S-containing HBsAg overcame this
      nonresponsiveness. In BALB/c (H-2d) and A/J (H-2a) mice, the pre-S-containing
      HBsAg induced higher hypersensitivity than did the major S protein. The
      enhancement induced by the pre-S region was demonstrated to occur during the
      induction phase by crisscross assay using pre-S-containing HBsAg and major S
      protein as Ag. The patterns of hypersensitivity induced by the major S, middle S
      (composed of major S and pre-S2), and large S (composed of middle S and pre-S1
      proteins) were also compared. The middle S protein induced responses of 1-h and
      24-h hypersensitivities in major S non-responder (C3H/He and CBA/J) mice, whereas
      the large S protein circumvented only the 1-h one. The effectiveness to stimulate
      hypersensitivities in vivo by HBsAg is in the following order: middle S greater
      than large S greater than major S. These data suggest that the pre-S region of
      HBsAg particle can enhance both the 1-h and 24-h hypersensitivities in the
      afferent phase.

PMID- 1375248
TI  - Tyrosine phosphorylation is required for mast cell activation by Fc epsilon RI
      cross-linking.
AB  - We investigated the possible role of tyrosine phosphorylation in the activation
      process of mast cells by cross-linking of cell-bound IgE antibodies. Bone marrow
      derived mouse mast cells (BMMC) were sensitized with mouse IgE antiDNP mAb and
      then challenged with multivalent Ag DNP conjugates of human serum albumin.
      Analysis of phosphotyrosine-containing proteins in their lysates by SDS-PAGE and
      immunoblotting revealed that cross-linking of cell-bound IgE antibodies induced a
      marked increase in tyrosine phosphorylation of several proteins. To obtain direct
      evidence for activation of protein-tyrosine kinases (PTK), phosphotyrosine
      containing proteins in lysates of mast cells were affinity purified, and kinase
      activity of the immunoprecipitates was assessed by an in vitro kinase assay. The
      results clearly showed activation of PTK upon cross-linking of Fc epsilon RI.
      Activation of PTK was not detected by the same assay when the sensitized BMMC
      were challenged with monovalent DNP-lysine. Treatment of sensitized BMMC with
      either Ca2+ ionophore or PMA failed to induce the activation of PTK. A
      representative IgE-independent secretagogue, thrombin, induced histamine release
      from BMMC but failed to induce activation of PTK. The results excluded the
      possibility that PTK activation is the consequence of an increase in
      intracellular Ca2+ or activation of protein kinase C. Addition of genistein, a
      PTK inhibitor, to sensitized BMMC before Ag challenge inhibited not only Ag
      induced PTK activation, but also inositol 1,4,5-trisphosphate production, and
      histamine release in a similar dose-response relationship. Other PTK inhibitors,
      such as lavendustin A and tyrphostin RG50864, also inhibited the Ag-induced
      activation of PTK and histamine release. The results collectively suggest that
      activation of PTK is an early event upstream of the activation of phospholipase
      C, and is involved in transduction of IgE-dependent triggering signals to
      mediator release.

PMID- 1375251
TI  - Regulation of keratin gene expression: the role of the nuclear receptors for
      retinoic acid, thyroid hormone, and vitamin D3.
AB  - Keratinization, the orderly process of differentiation of epidermal keratinocytes
      from stratum basale to stratum corneum, is influenced by hormones and vitamins.
      We have used expression of epidermal keratins as a paradigm of keratinization
      processes and analyzed the effects of retinoic acid, thyroid hormone, and vitamin
      D3 on keratin gene expression. DNA constructs in which keratin gene promoters
      drive expression of reporter genes were co-transfected with vectors expressing
      nuclear receptors for the above molecules into various cell types. The keratin
      promoters studied included K3, K5, K10, K14, and K16. The recipient cell types
      were HeLa and primary cultures of rabbit corneal and esophageal epithelial cells
      and of human epidermal keratinocytes. We found that retinoic acid, via its
      nuclear receptor, suppresses expression of all the above-listed keratin genes.
      Thyroid hormone and its receptor similarly suppressed those genes. The site of
      interaction between these two receptors and the promoter sequences of K10 and K14
      genes has been identified. Surprisingly, vitamin D3 and its receptor had no
      direct effect on keratin promoters. Our results suggest that a retinoic acid has
      a twofold effect on keratin gene expression: by regulating keratinocyte
      differentiation it determines which keratins are expressed, basal cell specific
      or differentiation specific; by direct interaction between its receptor and
      keratin genes, retinoic acid determines the total amount of keratin protein
      within the cell. Vitamin D3, on the other hand, also regulates keratinocyte
      differentiation, but does not directly interact with the keratin genes.

PMID- 1375250
TI  - Cells expressing an H chain Ig gene carrying a viral T cell epitope are lysed by
      specific cytolytic T cells.
AB  - The epitope corresponding to amino acid residues 147-161 of the nucleoprotein
      (NP) of influenza A virus is recognized by CTL in association with H-2Kd class I
      Ag. Herein, we engineered an Ig molecule carrying this CTL epitope by replacing
      the diversity gene segment of the H chain V region of an anti-arsonate antibody
      with an oligonucleotide that encodes the CTL epitope. The chimeric H chain gene
      was expressed either alone or together with the parental L chain in the
      nonsecreting BALB/c myeloma B cell line, SP2/0. The Ig produced by cells
      transfected with both the chimeric H chain and parental L chains genes expressed
      the NP epitope but lost the original arsonate binding activity. In addition,
      SP2/0 cells expressing the chimeric H chain either alone or together with the
      parental L chain were lysed by class I restricted NP-epitope specific CTL. By
      contrast, SP2/0 cells pulsed with soluble chimeric Ig molecules were not lysed by
      the specific CTL. These observations indicate that: 1) this particular CTL
      epitope can be expressed on Ig molecules without altering the H and L chain
      pairing; 2) this CTL epitope can be generated from this chimeric Ig in which it
      is surrounded by flanking regions distinct from those of the viral NP; and 3) the
      generation of this CTL epitope from the Ig molecule requires the endogenous
      pathway as do viral proteins.

PMID- 1375252
TI  - Synthetic peptides and anti-idiotypic antibodies as immunogens for the induction
      of antibody response to Haemophilus influenzae type b.

PMID- 1375253
TI  - Recombinant porin of Haemophilus influenzae type b.
AB  - A protein of approximately 40 kDa in the outer membrane of Haemophilus influenzae
      type b (Hib) behaves as a porin and permits transmembrane diffusion of low
      molecular-weight solutes. The gene for Hib porin was cloned from an M13 library
      of chromosomal DNA of Hib strain ATCC9795. The gene was subcloned into a new
      transfer vector as a prerequisite for its use in the baculovirus expression
      vector system. Pure recombinant virus (AcPORIN) was isolated. On infection of a
      cultivated insect cell line Sf9 with AcPORIN, a novel protein was detected in
      cell lysates, and this novel protein reacted with an anti-Hib porin monoclonal
      antibody. The purified recombinant Hib porin was tested for its pore-forming
      properties in a synthetic black lipid membrane. The biophysical activity of
      purified recombinant Hib porin was identical to porin isolated from the bacterial
      outer membrane.

PMID- 1375254
TI  - Cloning and analysis of lipooligosaccharide synthesis genes of Haemophilus
      influenzae type b that assemble or expose a 2-keto-3-deoxyoctulosonic acid
      epitope in Escherichia coli.

PMID- 1375255
TI  - Characterization of the human IgG antibody VL repertoire to Haemophilus
      influenzae type b polysaccharide.
AB  - The human antibody response to the capsular polysaccharide of Haemophilus
      influenzae type b (Hib) is a good model for examining human V region repertoires.
      While the VL repertoire of human antibodies to Hib polysaccharide is relatively
      simple and dominated by the product of a germline V kappa II gene named A2, at
      least five other VL genes can be expressed by some individuals. These include at
      least two V kappa I products and at least one V kappa III, one V kappa IV, and
      one V lambda product. The epitope recognized by a monoclonal anti-idiotype
      antibody is on the A2 V kappa II product.

PMID- 1375256
TI  - Outer membrane proteins P1 and P2 of Haemophilus influenzae type b: structure and
      identification of surface-exposed epitopes.
AB  - The outer membrane proteins (OMPs) P1 and P2 of Haemophilus influenzae type b
      exhibit molecular size and antigenic variation. Their structural genes have been
      cloned from prototype isolates of the most common disease-producing clonal
      groups. The derived amino acid sequences of P1 from strains of OMP subtypes 1H,
      3L, and 6U have three variable regions between highly conserved regions. An
      immunodominant surface-exposed epitope was identified near the carboxyl terminus
      of P1 proteins from subtype 1H and 3L strains. The P2 genes from subtype 1H, 1L,
      and 3L isolates were identical. The P2 gene sequence from a subtype 6U isolate
      differs from the subtype 1H P2 gene by 13 nucleotides, resulting in 10 amino acid
      changes. The P2 gene from a subtype 2L isolate differs by 1 nucleotide from the
      subtype 1H P2 gene, resulting in 1 amino acid change at position 166. Two surface
      exposed epitopes of OMP P2 were identified, one each between residues 158 and 174
      and residues 319 and 341.

PMID- 1375257
TI  - The contents of macromolecule solutes in flexor tendon sheath fluid and their
      relation to synovial fluid. A quantitative analysis.
AB  - The importance of synovial environment for minimal adhesion formation in flexor
      tendon healing has recently gained attention. Various techniques have been used
      to restore an injured synovial tendon sheath. Therefore a quantitative analysis
      of flexor tendon sheath fluid is of interest to increase our knowledge about the
      specific synovial milieu and to evaluate the success of different types of sheath
      reconstructions from a biochemical point of view. Samples of tendon sheath fluid
      from trigger digits and tendon sheaths containing ganglions have been assayed for
      contents of hyaluronic acid and proteins of different molecular weights. The
      results show concentrations of hyaluronate and several proteins similar to those
      in normal joint fluid. These results indicate that flexor tendon sheath fluid has
      a character similar to synovial fluid of joints and apparently has specific
      functions such as soft tissue lubrication and nutrition of avascular tendon
      tissue.

PMID- 1375258
TI  - Characterization of a vasodilator from the salivary glands of the yellow fever
      mosquito Aedes aegypti.
AB  - Salivary gland homogenates and oil-induced saliva of the mosquito Aedes aegypti
      dilate the rabbit aortic ring and contract the guinea pig ileum. The vasodilatory
      activity is endothelium-dependent, heat-stable, sensitive to both trypsin and
      chymotrypsin treatments, and both smooth muscle activities cross-desensitize to
      the tachykinin peptide substance P. Both bioactivities co-elute when salivary
      gland homogenates are fractionated by reversed-phase HPLC. Molecular sieving
      chromatography indicates a relative molecular mass of 1400. A monoclonal antibody
      specific to the carboxy terminal region of tachykinins reacts with material in
      the posterior part of the central lobe of paraformaldehyde-fixed salivary glands.
      The presence of a vasodilatory peptide of the tachykinin family in the salivary
      glands of A. aegypti is proposed and its role in blood feeding is discussed.

PMID- 1375259
TI  - Lymphocyte adhesion through very late antigen 4: evidence for a novel binding
      site in the alternatively spliced domain of vascular cell adhesion molecule 1 and
      an additional alpha 4 integrin counter-receptor on stimulated endothelium.
AB  - Recent studies demonstrate that alternative splicing of mRNA from a single gene
      can produce two forms of vascular cell adhesion molecule 1 (VCAM-1): a six
      immunoglobulin (Ig) domain form (VCAM-6D) and a seven-Ig domain form (VCAM-7D).
      Using a COS cell transient expression assay, we investigated whether VCAM-6D and
      VCAM-7D differ functionally in adhesion to the integrin VLA-4 (CD49d/CD29) on
      lymphoid cells. Binding of lymphoid cell lines and peripheral blood lymphocytes
      was completely blocked by VLA-4 monoclonal antibody (mAb) and one VCAM-1 mAb
      (4B9) to both VCAM-6D and VCAM-7D, whereas one VCAM-1 mAb (E1/6) completely
      blocked binding to VCAM-6D but only partially inhibited binding to VCAM-7D. We
      conclude that there is one VLA-4 binding site in the six Ig domains shared
      between VCAM-6D and VCAM-7D, and that the alternatively spliced domain 4 present
      in VCAM-7D provides a second VLA-4 binding site that is blocked by 4B9 but not
      the E1/6 mAb. We compared the inhibitory effects of anti-VCAM-1 and anti-VLA-4
      mAbs on lymphoid cell adhesion to cultured human umbilical vein endothelial cells
      (HUVEC). The anti-VCAM-1 mAb 4B9 blocked the binding of PBL and lymphoid tumor
      cells to stimulated HUVEC better than the anti-VCAM-1 mAb E1/6. Because VCAM-7D
      is the predominant form of VCAM-1 expressed by stimulated endothelial cells, this
      difference in VCAM-1 mAb inhibition is attributed to lymphoid cell binding to
      VCAM-7D on stimulated HUVEC. Although the anti-VLA-4 mAb and anti-VCAM-1 mAb 4B9
      equally inhibited PBL binding to stimulated HUVEC, mAb 4B9 inhibited the binding
      of two lymphoid cell lines significantly less than anti-VLA-4 mAb. Combination of
      4B9 mAb with function-blocking antiserum to human fibronectin, a second known
      ligand for VLA-4, also failed to inhibit as much as anti-VLA-4 mAb. These
      findings suggest that adhesion of lymphoid cell lines through VLA-4 or other
      alpha 4 integrins may involve inducible counter-receptor(s) on endothelium
      distinct from either VCAM-1 or fibronectin. Time course experiments indicate that
      the fraction of alpha 4 integrin-dependent binding that can be blocked by anti
      VCAM-1 mAb E1/6 rises and peaks within 2 h of tumor necrosis factor (TNF)
      stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375260
TI  - Rhodamine123 reveals heterogeneity within murine Lin-, Sca-1+ hemopoietic stem
      cells.
AB  - Murine bone marrow Lin-, Ly6A/E+ cells have been fractionated on the basis of
      rhodamine123 retention into Rh123med/hi and Rh123lo subpopulations. These
      populations have different responses to hemopoietic growth factors with respect
      to in vitro colony formation. Cells from either fraction were not stimulated by
      only granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage colony
      stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF),
      interleukins 1 and 6 (IL-1 and -6), or leukemia inhibitory factor (LIF) alone.
      The Rh123med/hi, but not the Rh123lo fraction, contained cells that could be
      stimulated by either stem cell factor (SCF) or IL-3 alone. When combinations of
      growth factors were added, the Rh123med/hi fraction produced more colonies, and
      responded to a wider range of factor combinations than the Rh123lo population.
      When tested in vivo, both populations contained no detectable day 8 colony
      forming unit-spleen (CFU-S), and similar frequencies of day 13 CFU-S. When
      transplanted into lethally irradiated recipients (100 cells/recipient),
      significant numbers of donor cells (67-73%) were found in the peripheral blood of
      Rh123lo recipients. Both myeloid and lymphoid cells were of donor origin. By
      comparison, the Rh123med/hi population produced recipients with 1-2% donor cells
      in peripheral blood, the majority of which were lymphoid.

PMID- 1375261
TI  - A Trypanosoma cruzi membrane protein shares an epitope with a lymphocyte
      activation antigen and induces crossreactive antibodies.
AB  - Chagas' disease results from the infection of the protozoan parasite Trypanosoma
      cruzi and affects several million people in South America. Several alterations of
      the immune response have been described in this disease, such as severe
      immunosuppression of both cellular and humoral responses and massive polyclonal
      stimulation with the generation of autoantibodies crossreacting with host cells
      and tissues. We have obtained monoclonal antibodies (mAbs) from T. cruzi-infected
      mice that recognized a 50/55-kD antigen (GP50/55) on the T. cruzi membrane, but
      not in other parasites of the family Trypanosomatidae. One of these GP50/55
      specific mAbs (C10) crossreacts with a 28-kD antigen (p28) expressed on the
      membrane of greater than 85% of activated mouse T and B lymphocytes, after in
      vitro activation with concanavalin A, Salmonella typhosa lipopolysaccharide,
      phorbol dibutyrate ester, or antigen, and on several murine T and B lymphocyte
      cell lines. Human T and B lymphocytes also express upon activation with
      phytohemagglutinin or Staphylococcus aureus Cowan I (SAC) a similar antigen
      recognized by mAb C10, although in a lower proportion of cells (30-40%).
      Furthermore, this mAb was able to suppress mouse and human T and B cell
      proliferation to any of those stimuli. In addition, sera from chagasic patients
      and T. cruzi-infected mice, but not from control patients or littermates, contain
      antibodies that recognize a similar p28 antigen on B lymphocytes. Furthermore,
      the immunoglobulin fractions of some chagasic sera also suppress the
      proliferation of human T lymphocytes. These results suggest a possible
      pathological role of autoantibodies as an alternative mechanism for T. cruzi
      associated immunosuppression.

PMID- 1375262
TI  - Differential regulation of T cell antigen responsiveness by isoforms of the src
      related tyrosine protein kinase p59fyn.
AB  - Recent observations suggest that the src-related tyrosine protein kinase p59fyn
      may be involved in antigen-induced T lymphocyte activation. As a result of
      alternative splicing, p59fyn exists as two isoforms that differ exclusively
      within a short sequence spanning the end of the Src Homology 2 (SH2) region and
      the beginning of the tyrosine protein kinase domain. While one p59fyn isoform
      (fynB) is highly expressed in brain, the alternative product (fynT) is
      principally found in T lymphocytes. To further understand the role of p59fyn in T
      cell activation and to test the hypothesis that p59fynT serves a tissue-specific
      function in T lymphocytes, we have examined the effects of expression of
      activated versions (tyrosine 528 to phenylalanine 528 mutants) of either form of
      p59fyn on the physiology of an antigen-specific mouse T cell hybridoma. Our
      results demonstrated that the two forms of fyn, expressed in equivalent amounts,
      efficiently enhanced antibody-induced T cell receptor (TCR)-mediated signals. In
      contrast, only p59fynT increased interleukin 2 production in response to antigen
      stimulation. This finding implies that the distinct p59fyn isoform expressed in T
      lymphocytes regulates the coupling of TCR stimulation by antigen/major
      histocompatibility complex to lymphokine production.

PMID- 1375263
TI  - Long-term erythropoiesis from constant numbers of CD34+ cells in serum-free
      cultures initiated with highly purified progenitor cells from human bone marrow.
AB  - To directly study the biological properties of purified hematopoietic colony
      forming cell precursors, cells with a CD34+ CD45RAlo CD71lo phenotype were
      purified from human bone marrow using density separation and fluorescence
      activated cell sorting, and were cultured in serum-free culture medium
      supplemented with various cytokines. In the presence of interleukin 3 (IL-3), IL
      6, erythropoietin, and mast cell growth factor (a c-kit ligand), cell numbers
      increased approximately 10(6)-fold over a period of 4 wk, and the percentage of
      cells that expressed transferrin receptors (CD71) increased from less than 0.1%
      at day 0 to greater than 99% at day 14. Interestingly, the absolute number of
      CD34+ CD71lo cells did not change during culture. When CD34+ CD71lo cells were
      sorted from expanded cultures and recultured, extensive cell production was
      repeated, again without significant changes in the absolute number of cells with
      the CD34+ CD71lo phenotype that were used to initiate the (sub)cultures. These
      results document that primitive hematopoietic cells can generate progeny without
      an apparent decrease in the size of a precursor cell pool.

PMID- 1375264
TI  - Comparison of human B cell antigen receptor complexes: membrane-expressed forms
      of immunoglobulin (Ig)M, IgD, and IgG are associated with structurally related
      heterodimers.
AB  - We have recently reported that on human B lymphocytes, membrane IgM (mIgM)
      associates with a heterodimer of 47- and 37-kD polypeptides, the 47-kD subunit
      being encoded by the mb-1 gene. We show here that expression of mb-1, both at the
      mRNA and the protein level, is not restricted to IgM+ B cells but can also be
      found in IgM- pre-B cells and mIgM-IgG+ B cells. Membrane forms of IgD and IgG,
      isolated from freshly isolated human B cells and B cell lines, are expressed
      together with heterodimeric protein structures biochemically similar to the mIgM
      associated polypeptides, and these were shown to comprise the products of the mb
      1 and B29 genes, or homologous genes. Finally, all three classes of antigen
      receptors are linked to protein kinases, capable of phosphorylating the Ig
      associated heterodimers. Our findings provide insight in the structural
      organization of the different antigen receptors on human B cells and have
      implications for their function.

PMID- 1375265
TI  - CD8+ T cells specific for a single nonamer epitope of Listeria monocytogenes are
      protective in vivo.
AB  - Class I major histocompatibility complex (MHC)-restricted CD8+ T cells have been
      demonstrated to be effective mediators of both acquired and adoptive immunity to
      the intracellular bacterium Listeria monocytogenes. We have recently determined
      that L. monocytogenes-infected H-2d mice recognize a nonamer peptide, residues 91
      99, of the secreted protein listeriolysin O (LLO), in a H-2Kd-restricted fashion.
      In this report we have generated CD8+ T cell lines with specificity for LLO 91-99
      in the context of H-2Kd by in vitro stimulation with P815 (H-2d) cells
      transfected with LLO. These CD8+ lines have been generated from immune donors
      after sublethal infection with L. monocytogenes, or after in vivo immunization
      with syngeneic spleen cells coated with synthetic LLO 91-99 peptide. LLO-specific
      CD8+ T cells derived from either protocol were capable of significant protection
      against L. monocytogenes infection. The in vivo protection by these CD8+ T cell
      lines has been shown to be solely due to recognition of LLO 91-99 in the context
      of H-2Kd. These studies demonstrate that CD8+ T cell immunity to a single,
      naturally produced peptide epitope has the potential for significant protection
      in a bacterial infection. Thus, the allele-specific motif approach to epitope
      prediction has identified a naturally produced bacterial epitope with biological
      relevance.

PMID- 1375266
TI  - Characterization of a functionally important and evolutionarily well-conserved
      epitope mapped to the short consensus repeats of E-selectin and L-selectin.
AB  - Selectins represent a new family of adhesion molecules, expressed by leukocytes
      and endothelial cells, that are involved in the regulation of leukocyte traffic.
      Here we have characterized a new monoclonal antibody (mAb) (EL-246) that
      recognizes both human leukocyte L-selectin (previously called LAM-1, LECAM-1, or
      gp90MEL-14) and endothelial cell E-selectin (previously called ELAM-1). EL-246
      recognized a 110-kD protein expressed on cells transfected with E-selectin cDNA
      and stained many postcapillary venules in inflamed human tonsil. EL-246 also
      stained human peripheral blood leukocytes and showed identity with anti-L
      selectin mAb in two-color flow cytometric analysis. The expression of the
      leukocyte EL-246 antigen was regulated in the same manner as L-selectin and EL
      246 recognized anti-L-selectin mAb affinity-purified antigen in SDS/PAGE Western
      blot analysis. Further, L-selectin cDNA transfectants were specifically stained
      by EL-246. EL-246 blocked greater than 95% of lymphocyte adhesion to peripheral
      lymph node high endothelial venules and greater than 90% of neutrophil adhesion
      to E-selectin transfectants. In addition to the EL-246 epitope being expressed on
      two different human selectins, it was detected on L-selectin from a variety of
      different animals. Interestingly, domain mapping studies localized the EL-246
      epitope to the short consensus repeat (SCR) domains of L-selectin. EL-246 is the
      first mAb that recognizes two different selectins and potentially defines a
      functional epitope encoded by the SCR domains. Inhibitors of selectin function
      targeted to this region would be expected to have the added advantage of
      simultaneously blocking the activity of two distinct adhesion proteins involved
      in inflammation.

PMID- 1375267
TI  - T cell recognition of self-human histocompatibility leukocyte antigens (HLA)-DR
      peptides in context of syngeneic HLA-DR molecules.
AB  - It has been suggested that self major histocompatibility complex (MHC) peptides
      bound to self MHC molecules may be involved in the intrathymic induction of self
      tolerance. We studied the antigenicity of synthetic peptides derived from the
      first domain of DR beta 1*0101 chain in a DR beta 1*0101 responder. We found that
      a peptide corresponding to residues 21-42 of the beta chain could elicit the
      proliferation of autoreactive T cells. A T cell line (TCL-SUN) and 7 of 9 T cell
      clones (TCC) derived from TCL-SUN specifically recognized peptide 21-42 in the
      presence of APCs carrying the DR beta 1*0101 allele. DR beta 1*0101 positive APCs
      stimulated the TCCs in the absence of peptide, although the magnitude of the
      response was much lower than in cultures with peptide. This suggests that self
      DR1 molecules are continuously processed into peptides that are presented by the
      DR1 molecules on the surface of the cells. The data indicate that some T cells
      whose TCR binds to self MHC peptides presented by self MHC molecules are not
      deleted, although their ligand is continuously present. TCCs specific for peptide
      21-42 presented in the context of DR1 were also stimulated by cells heterozygous
      for DR beta 1*0301 and 1601, indicating that some DR peptide-specific
      autoreactive T cells participate in alloreactivity.

PMID- 1375268
TI  - Role of a major autoepitope in forming the DNA binding site of the p70 (Ku)
      antigen.
AB  - The Ku antigen is a heterodimer consisting of 70- and 80-kD protein subunits that
      binds to termini of double-stranded DNA. DNA binding appears to be mediated
      partly by the 70-kD (p70) subunit, but the precise mechanism of its association
      with DNA is unclear. High-titer autoantibodies in sera from certain patients with
      systemic lupus erythematosus recognize at least eight distinct epitopes of Ku,
      and inhibit DNA binding. In the present studies, the binding of DNA to truncated
      p70 fusion proteins was determined in Southwestern blots and DNA
      immunoprecipitation assays. Appropriate folding of the p70 protein was crucial
      for efficient DNA binding. The minimal DNA binding site, amino acids 536-609,
      contains a major conformational autoepitope of p70 (amino acids 560-609).
      Deletion of amino acids 601-609, or substitution of ala-ala-ala for lys-ser-gly
      at positions 591-593, eliminated DNA binding as well as autoantibody binding,
      suggesting that the same secondary or supersecondary structure is involved in
      both DNA binding and autoantibody recognition. Residues within the DNA binding
      site/autoepitope closely resemble the helix-turn-helix motif in bacteriophage
      lambda Cro protein and certain other DNA binding proteins, and mutations
      predicted to destabilize this structure eliminated DNA binding. Adjacent to the
      helix-turn-helix is a highly basic domain (positions 539-559) that was also
      required for DNA binding. The findings suggest that the DNA binding site of p70
      consists of a basic domain adjacent to a helix-turn-helix structure that also
      forms a major autoepitope.

PMID- 1375271
TI  - Monocyte attachment to activated human vascular endothelium in vitro is mediated
      by leukocyte adhesion molecule-1 (L-selectin) under nonstatic conditions.
AB  - The receptors that mediate monocyte adhesion to cytokine-stimulated endothelial
      monolayers were assessed using a nonstatic (rotating) cell-attachment assay. In
      this system, leukocyte adhesion molecule-1 (LAM-1) (L-selectin) mediated a major
      portion (87 +/- 15% at 37 degrees C) of monocyte attachment to activated
      endothelium. mAb blocking of endothelial leukocyte adhesion molecule-1 (41%
      inhibition), CD18 (36%), and vascular cell adhesion molecule-1 (25%) function had
      lesser effects on attachment. These results suggest that LAM-1 may serve an
      important role in monocyte attachment to endothelium at sites of inflammation.

PMID- 1375269
TI  - Transfection of CD14 into 70Z/3 cells dramatically enhances the sensitivity to
      complexes of lipopolysaccharide (LPS) and LPS binding protein.
AB  - Bacterial endotoxin (lipopolysaccharide [LPS]) causes fatal shock in humans and
      experimental animals. The shock is mediated by cytokines released by direct LPS
      stimulation of cells of monocytic origin (monocyte/macrophage [MO]). Recent
      studies have supported the concept that the plasma protein, LPS binding protein
      (LBP), plays an important role in controlling MO responses to LPS. Specifically,
      evidence has been presented to suggest that CD14, a membrane protein present in
      MO, serves as a receptor for complexes of LPS and the plasma protein LPS binding
      protein (LBP). In this function CD14 mediates attachment of LPS-bearing particles
      opsonized with LBP and appears to play an important role in regulating cytokine
      production induced by complexes of LPS and LBP. The CD14-, murine pre-B cell line
      70Z/3 responds to LPS by synthesis of kappa light chains and consequent
      expression of surface IgM. To better understand the role of CD14 in controlling
      cellular responses to LPS, we investigated the effect of transfection of CD14
      into 70Z/3 cells on LPS responsiveness. We report here that transfection of human
      or rabbit CD14 cDNA into 70Z/3 cells results in membrane expression of a glycosyl
      phosphatidylinositol-anchored CD14. When LPS is complexed with LBP, CD14-bearing
      70Z/3 cells bind more LPS than do the parental or 70Z/3 cells transfected with
      vector only. Remarkably, the expression of CD14 lowers the amount of LPS required
      to stimulate surface IgM expression by up to 10,000-fold when LPS dose-response
      curves in the CD14-, parental and CD14-bearing, transfected 70Z/3 cells are
      compared. In contrast, the response of CD14-bearing 70Z/3 cells and the parental
      70Z/3 cell line (CD14-) to interferon gamma is indistinguishable. LPS stimulation
      of the parental and CD14-bearing 70Z/3 cells results in activation of NF-kB.
      These data provide evidence to support the concept that the LPS receptor in cells
      that constitutively express CD14 may be a multiprotein complex containing CD14
      and membrane protein(s) common to a diverse group of LPS-responsive cells.

PMID- 1375270
TI  - Tumor necrosis factor alpha directly and indirectly regulates hematopoietic
      progenitor cell proliferation: role of colony-stimulating factor receptor
      modulation.
AB  - Tumor necrosis factor alpha (TNF-alpha) has been shown to both stimulate and
      inhibit the proliferation of hematopoietic progenitor cells (HPCs) in vitro, but
      its mechanisms of action are not known. We demonstrate that the direct effects of
      TNF-alpha on murine bone marrow progenitors are only inhibitory and mediated at
      least in part through downmodulation of colony-stimulating factor receptor (CSF
      R) expression. The stimulatory effects of TNF-alpha are indirectly mediated
      through production of hematopoietic growth factors, which subsequently results in
      increased granulocyte-macrophage CSF and interleukin 3 receptor expression. In
      addition, the effects of TNF-alpha (stimulatory or inhibitory) are strictly
      dependent on the particular CSF stimulating growth as well as the concentration
      of TNF-alpha present in culture. A model is proposed to explain how TNF-alpha
      might directly and indirectly regulate HPC growth through modulation of CSF-R
      expression.

PMID- 1375272
TI  - Self-peptide released from class II HLA-DR1 exhibits a hydrophobic two-residue
      contact motif.
AB  - Peptide fragments of foreign and self-proteins are of great immunologic
      importance as their binding to major histocompatibility complex (MHC) class I or
      II molecules makes an interaction with a corresponding T cell receptor possible.
      Recently, allele-specific peptide sequence motifs proved to be responsible for
      MHC binding, no matter whether self- or non-self-antigens were involved. Up to
      now, all investigated human class II-associated peptides were derived from
      foreign antigenic proteins. Therefore, we undertook sequence and binding analyses
      with a 16-mer self-peptide (SP3) that has been eluted from HLA-DR1. Here we
      demonstrate, by synthetic polyalanine-based 13-mer analogues of SP3, that two
      bulky hydrophobic anchor residues with relative spacing i, i + 8 are sufficient
      for high affinity binding. This is consistent with the hydrophobic i, i + 8
      binding pattern recently found for DR-restricted T cell epitopes. Nevertheless,
      highly helical alanine-based design peptides with anchor spacing i, i + 9 exhibit
      maximal affinity, whereas replacement of alanine by helix destabilizing proline
      abrogates binding. Thus, a two-residue contact motif is the common minimal
      requirement of self- and foreign peptides for high affinity anchoring to HLA-DR1.
      In contrast to class I, the anchor spacing of DR1-associated peptides seems to
      bear some variability due to conformational diversity.

PMID- 1375273
TI  - Pseudo-streaming potentials in Necturus gallbladder epithelium. I. Paracellular
      origin of the transepithelial voltage changes.
AB  - Apparent streaming potentials were elicited across Necturus gallbladder
      epithelium by addition or removal of sucrose from the apical bathing solution. In
      NaCl Ringer's solution, the transepithelial voltage (Vms) change (reference,
      basolateral solution) was positive with sucrose addition and negative with
      sucrose removal. Bilateral Cl- removal (cyclamate replacement) had no effect on
      the polarity or magnitude of the Vms change elicited by addition of 100 mM
      sucrose. In contrast, bilateral Na+ removal (tetramethylammonium [TMA+]
      replacement) inverted the Vms change (from 2.7 +/- 0.3 to -3.2 +/- 0.2 mV).
      Replacement of Na+ and Cl- with TMA+ and cyclamate, respectively, abolished the
      change in Vms. Measurements of cell membrane voltages and relative resistances
      during osmotic challenges indicate that changes in cell membrane parameters do
      not explain the transepithelial voltage changes. The initial changes in Vms were
      slower than expected from concomitant estimates of the time course of sucrose
      concentration (and hence osmolality) at the membrane surface. Paired recordings
      of the time courses of paracellular bi-ionic potentials (partial substitution of
      apical Na+ with tetrabutylammonium [TBA+]) revealed much faster time courses than
      those produced by sucrose addition, although the diffusion coefficients of
      sucrose and TBACl are similar. Hyperosmotic and hypoosmotic challenges yielded
      initial Vms changes at the same rate; thereafter, the voltage increased with
      hypoosmotic solution and decreased with hyperosmotic solution. These late voltage
      changes appear to result from changes in width of the lateral intercellular
      spaces. The early time courses of the Vms changes produced by osmotic challenge
      are inconsistent with the expectations for water-ion flux coupling in the
      junctions. We propose that they are pseudo-streaming potentials, i.e., junctional
      diffusion potentials caused by salt concentration changes in the lateral
      intercellular spaces secondary to osmotic water flow.

PMID- 1375274
TI  - Anion permeation in an apical membrane chloride channel of a secretory epithelial
      cell.
AB  - Single channel currents though apical membrane Cl channels of the secretory
      epithelial cell line T84 were measured to determine the anionic selectivity and
      concentration dependence of permeation. The current-voltage relation was
      rectified with single channel conductance increasing at positive potentials. At 0
      mV the single channel conductance was 41 +/- 2 pS. Permeability, determined from
      reversal potentials, was optimal for anions with diameters between 0.4 and 0.5
      nm. Anions of larger diameter had low permeability, consistent with a minimum
      pore diameter of 0.55 nm. Permeability for anions of similar size was largest for
      those ions with a more symmetrical charge distribution. Both HCO3 and H2PO4 had
      lower permeability than the similar-sized symmetrical anions, NO3 and ClO4. The
      permeability sequence was SCN greater than I approximately NO3 approximately ClO4
      greater than Br greater than Cl greater than PF6 greater than HCO3 approximately
      F much greater than H2PO4. Highly permeant anions had lower relative single
      channel conductance, consistent with longer times of residence in the channel for
      these ions. The conductance sequence for anion efflux was NO3 greater than SCN
      approximately ClO4 greater than Cl approximately I approximately Br greater than
      PF6 greater than F approximately HCO3 much greater than H2PO4. At high internal
      concentrations, anions with low permeability and conductance reduced Cl influx
      consistent with block of the pore. The dependence of current on Cl concentration
      indicated that Cl can also occupy the channel long enough to limit current flow.
      Interaction of Cl and SCN within the conduction pathway is supported by the
      presence of a minimum in the conductance vs. mole fraction relation. These
      results indicate that this 40-pS Cl channel behaves as a multi-ion pathway in
      which other permeant anions could alter Cl flow across the apical membrane.

PMID- 1375276
TI  - Retrovirus-like particles from the human T47D cell line are related to mouse
      mammary tumour virus and are of human endogenous origin.
AB  - Retrovirus-like particles were secreted in a steroid-dependent manner by the
      human mammary carcinoma cell line T47D. The particles exhibited typical
      retroviral properties such as their electron microscopic appearance (95 nm in
      diameter) and occasional budding, sedimentation at 1.14 g/ml, reverse
      transcriptase activity and genomic RNA. The T47D particles were related to mouse
      mammary tumour virus (MMTV) as shown by their ultrastructural appearance (B type
      like eccentric dense cores and budding), Mg2+ dependence of the reverse
      transcriptase activity; immunological reactivity with MMTV-directed antibodies
      (revealing proteins of 63K, 52K, 26K and 18K), and hybridization of particle RNA
      with MMTV DNA under stringent conditions. Purified particles were able to
      incorporate deoxynucleoside triphosphates in the absence of an exogenous primer
      and template, thus indicating the existence of a complete and biochemically
      functional reverse transcription apparatus (reverse transcriptase, RNA and
      primer) and the ability to direct endogenous cDNA synthesis. Labelled particle
      cDNA hybridized strongly to human genomic DNA but not to mouse and cat DNA, thus
      indicating the human origin of the T47D particles. Furthermore all human DNAs,
      hybridized with the labelled particle cDNA, showed a uniform hybridization
      pattern of restriction fragments, indicating the endogenous origin and
      distribution of the proviral particle DNA in the human genome.

PMID- 1375275
TI  - Properties of the calcium-activated chloride current in heart.
AB  - We used the whole cell patch clamp technique to study transient outward currents
      of single rabbit atrial cells. A large transient current, IA, was blocked by 4
      aminopyridine (4AP) and/or by depolarized holding potentials. After block of IA,
      a smaller transient current remained. It was completely blocked by nisoldipine,
      cadmium, ryanodine, or caffeine, which indicates that all of the 4AP-resistant
      current is activated by the calcium transient that causes contraction. Neither
      calcium-activated potassium current nor calcium-activated nonspecific cation
      current appeared to contribute to the 4AP-resistant transient current. The
      transient current disappeared when ECl was made equal to the pulse potential; it
      was present in potassium-free internal and external solutions. It was blocked by
      the anion transport blockers SITS and DIDS, and the reversal potential of
      instantaneous current-voltage relations varied with extracellular chloride as
      predicted for a chloride-selective conductance. We concluded that the 4AP
      resistant transient outward current of atrial cells is produced by a calcium
      activated chloride current like the current ICl(Ca) of ventricular cells (1991.
      Circulation Research. 68:424-437). ICl(Ca) in atrial cells demonstrated outward
      rectification, even when intracellular chloride concentration was higher than
      extracellular. When ICa was inactivated or allowed to recover from inactivation,
      amplitudes of ICl(Ca) and ICa were closely correlated. The results were
      consistent with the view that ICl(Ca) does not undergo independent inactivation.
      Tentatively, we propose that ICl(Ca) is transient because it is activated by an
      intracellular calcium transient. Lowering extracellular sodium increased the peak
      outward transient current. The current was insensitive to the choice of sodium
      substitute. Because a recently identified time-independent, adrenergically
      activated chloride current in heart is reduced in low sodium, these data suggest
      that the two chloride currents are produced by different populations of channels.

PMID- 1375277
TI  - Antibodies are produced to the variable regions of the external envelope
      glycoprotein of human immunodeficiency virus type 1 in chimpanzees infected with
      the virus and baboons immunized with a candidate recombinant vaccine.
AB  - Chimpanzees infected with human immunodeficiency virus type 1 produce antibodies
      against the variable regions of the external envelope glycoprotein gp120. All
      five variable regions contain an epitope which is recognized by at least one of
      five chimpanzee sera. Each of the sera recognized a different pattern of
      epitopes. It is suggested that this varying response contributes to the emergence
      of variant viruses in the host. In contrast with the variability of the
      chimpanzees' response to replicating virus, that of baboons to a candidate
      recombinant vaccine is more uniform. Baboons injected with recombinant gp120
      produced high levels of antibodies to epitopes within both the variable and
      conserved regions which coincided with epitopes previously shown to induce
      neutralizing antibodies.

PMID- 1375278
TI  - Broad cross-reactivity with marked fine specificity in the cytotoxic T cell
      response to flaviviruses.
AB  - Cytotoxic T (Tc) cells were generated in mice of five H-2 haplotypes against the
      flaviviruses Kunjin and West Nile (WNV). A panel of recombinant vaccinia viruses
      which between them expressed cDNA of the entire Kunjin virus genome were used to
      infect targets. Anti-Kunjin virus responses to determinants derived from non
      structural proteins, especially NS3, NS4A and NS4B, were dominant in most mouse
      strains; usually only one class I major histocompatibility complex (MHC)
      restriction element was involved. WNV-immune Tc cells showed similar but not
      identical patterns of antigen recognition to Kunjin virus-immune Tc cells. The
      extent to which WNV-immune Tc cells recognized Kunjin virus-encoded determinants
      varied considerably between mice of different MHC haplotypes.

PMID- 1375279
TI  - Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin
      neuraminidase glycoprotein of Newcastle disease virus.
AB  - The majority of neutralizing monoclonal antibodies (MAbs) to the haemagglutinin
      neuraminidase (HN) glycoprotein of Newcastle disease virus prevent attachment of
      the virus to cellular receptors and inhibits virion-induced fusion from without
      (FFWO) and fusion from within (FFWI) mediated by the virus glycoprotein-laden
      infected cell surface. For these antibodies, the inhibition of fusion is presumed
      to be the result of the prevention of HN-mediated bridging of potential fusion
      partners. MAbs against antigenic sites 3 and 4 neutralize virus infectivity, but
      by a mechanism other than the prevention of attachment, the exact nature of which
      remains to be established. Antibodies to both of these sites effectively inhibit
      virion-induced FFWO, even when the inducing virus is not infectious. This is
      consistent with the mechanism of neutralization of these MAbs involving the
      inhibition of an early, post-attachment step in infection. MAbs to site 3 also
      inhibit FFWI, but those to site 4 do not, even when added at high concentrations.
      This suggests that the requirement for HN may be different in the two modes of
      fusion. The epitopes recognized by MAbs to sites 3 and 4 have been delineated by
      the identification of individual nucleotide substitutions in the HN genes of
      neutralization escape variants. Some of the deduced amino acid substitutions
      result in additional N-linked glycosylation sites in HN, which are utilized and
      presumably account for the escape from neutralization.

PMID- 1375280
TI  - Intracellular processing of the human respiratory syncytial virus fusion
      glycoprotein: amino acid substitutions affecting folding, transport and cleavage.
AB  - The intracellular processing and transport of the respiratory syncytial virus
      (RSV) fusion (F) glycoprotein was examined by comparing the maturation and
      stability of wild-type F, uncleaved mutant F and chimeric F glycoproteins
      expressed by recombinant vaccinia viruses to that of F protein expressed by RSV.
      One of the recombinant viruses, vF317, expressed F protein (F317) that was
      processed like the RSV F glycoprotein. F317 was synthesized initially as F0, the
      uncleaved glycosylated precursor of mature F protein, and formed stable
      oligomeric structures that were maintained following cleavage of F0 to form the
      disulphide bond-linked F1 and F2 subunits. Most of the newly synthesized F0
      expressed by either RSV or by vF317 was sensitive to treatment with
      endoglycosidase H (Endo H). Following cleavage of F0, F1 was resistant to Endo H,
      suggesting that conversion to complex-type sugars, which takes place in the
      medial Golgi apparatus, occurred simultaneously with or immediately prior to
      cleavage of F0 into F1 and F2. Another recombinant virus, vF313, synthesized only
      uncleaved F protein (F313) that comigrated with F0. Uncleaved F313 was expressed
      as a stable glycosylated protein; however, unlike cleaved F317, its
      oligosaccharides were not modified to complex forms, as determined from its Endo
      H sensitivity, and uncleaved F313 did not assemble into stable oligomeric
      structures. Nucleotide sequence analysis of the cDNA clones encoding F313 and
      F317 revealed four predicted amino acid sequence differences, none of which were
      located at the cleavage site. Expression of chimeric F proteins obtained by
      restriction fragment exchange between the two cDNA clones indicated that two
      amino acid changes in the F1 domain, located at amino acid residues 301 (Val to
      Ala) and 447 (Val to Met), resulted in the expression of uncleaved F protein. A
      change at either of these two amino acid residues, 301 or 447, resulted in the
      expression of inefficiently cleaved F protein, defining an additional F protein
      phenotype. Pulse-chase analyses to examine the association of recombinant F
      glycoproteins with gradient-purified fractionated membranes or with GRP78-BiP, a
      protein resident in the endoplasmic reticulum (ER) which binds to nascent
      proteins, revealed that uncleaved F protein (F313) is associated with GRP78-BiP
      in the ER for a longer time than F317, and little if any F313 was transported to
      the cell surface. In addition, the uncleaved F protein (F313) was not recognized
      by a panel of F protein-specific monoclonal antibodies in ELISA or indirect
      immunofluorescence assays, suggesting that F313 was misfolded and, as a result,
      not transported properly or cleaved.

PMID- 1375281
TI  - Abnormalities of epidermal differentiation associated with expression of the
      human papillomavirus type 1 early region in transgenic mice.
AB  - The promoter region of a keratin 6 (K6) gene was used to regulate expression of
      the early region of human papillomavirus type 1 (HPV-1e) in transgenic mice. In
      one line of mice the K6-HPV1e transgene was transcribed in several regions of the
      skin, the predominant transcript being a 1.1 kb RNA including the E4 open reading
      frame, and E1-E4 protein was detected in the upper suprabasal layers of the skin
      in paws and tail. A 1.7 kb RNA corresponding to the E6/E7 transcript was also
      prominent in tails of homozygous transgenic animals. In young homozygous
      transgenic mice the epidermis of the tail showed dysplasia and hyperplasia of the
      suprabasal layers with both hyperkeratosis and focal parakeratosis in the stratum
      corneum. A similar though milder phenotype was also observed sporadically in
      hemizygous transgenics. Analysis of the pattern of mouse keratins present in the
      affected tail skin showed strong up-regulation of the endogenous keratins 6 and
      16 throughout the basal and suprabasal layers, suggesting a positive feedback
      mechanism for the strong transgene activation. Expression of the major
      differentiation-specific keratins 1 and 10 was repressed. The pattern of E1-E4
      expression and the perturbation of normal epithelial differentiation parallel
      many of the characteristics of HPV-1 warts or verrucae, suggesting that HPV
      transgenic mice could be useful for analysis of the interactions of HPV gene
      products with cellular regulatory pathways within an otherwise normal epithelium.

PMID- 1375282
TI  - VVA-labelled cells in monkey visual cortex are double-labelled by a polyclonal
      antibody to a cell surface epitope.
AB  - The staining patterns produced by the lectin Vicia villosa and by a commercially
      available polyclonal antibody generated to substance P were analysed and compared
      in monkey visual cortex at the light and electron microscopic levels. Vicia
      villosa lectin labels the cell surface of a subpopulation of cortical cells,
      producing a meshlike pattern over the soma and proximal dendrites. The polyclonal
      antibody labels three distinct elements in the cortex: a pericellular epitope
      present on a subpopulation of non-pyramidal cells, and putative intracellular
      sites in a type of small pyramidal cell located at the layer 5/6 border, and in a
      small number of non-pyramidal cells in the underlying white matter. Because of
      the similarity of the appearance of the Vicia villosa lectin labelling and the
      pericellular labelling produced by the polyclonal antibody, further experiments
      were conducted to determine the relationship between the cell surface sites
      recognized by these markers. Double-labelling experiments show that both sites
      are present on the same population of cells, and at the ultrastructural level
      both markers appear to outline the intersynaptic cell membrane, sometimes
      extending around presynaptic elements. However, preadsorption experiments
      indicate that the markers recognize different sites on the cell membrane.
      Preadsorption experiments also show that the pericellular epitope recognized by
      the polyclonal antibody is unlikely to be substance P, but it may be structurally
      similar to keyhole limpet haemocyanin. Comparison of cortical and subcortical
      staining patterns produced with the polyclonal antibody and with a commonly used
      monoclonal antibody to substance P reveal that one of the putative intracellular
      epitopes recognized by the polyclonal antibody is likely to be substance P.

PMID- 1375283
TI  - Suramin: a novel growth factor antagonist with activity in hormone-refractory
      metastatic prostate cancer.
AB  - PURPOSE: Suramin is known to inhibit the growth of malignant prostate carcinoma
      cells in vitro. This led us to evaluate the effectiveness of suramin in the
      treatment of 38 patients with prostate carcinoma refractory to hormone therapy.
      PATIENTS AND METHODS: Suramin was administered by continuous infusion at a rate
      designed to reach a peak of 300 micrograms/mL at the end of 14 days. Patients
      were given 8 weeks to recover from any toxicity before beginning the second
      cycle. Subsequent cycles were administered in the same manner except the starting
      dose rate was 280 mg/m2. RESULTS: In 17 patients with measurable soft tissue
      disease, three had complete disappearance of soft tissue disease for 4, 5, and 11
      months, whereas three patients had a greater than or equal to 50% decrease in the
      sum of the products of the diameters of all measurable disease for greater than
      or equal to 1 month. Of these 17 patients, pretreatment prostate-specific antigen
      (PSA) decreased by 75% or more in five (29%) and normalized in one (6%). The
      remaining 21 patients had disease limited to bone, and only one of these
      experienced resolution of more than 50% of all lesions on bone scan. Of these 21
      patients, pretreatment PSA decreased by 75% or more in eight (38%) and normalized
      in five (25%). Median time to progression for all patients was 26.3 weeks, and
      median survival was 42.3 weeks. Patients with bone involvement alone exhibited a
      better survival than patients with soft tissue involvement (P2 = .02). Survival
      was strongly correlated (P2 = .0001) with a decline in the pretreatment PSA of
      greater than or equal to 75% by the eighth week on therapy, with nearly an 85%
      survival at 1 year compared with a 20% survival for those whose pretreatment PSA
      did not decline by that amount. CONCLUSION: We conclude that suramin is an active
      agent in hormone-refractory prostate carcinoma.

PMID- 1375284
TI  - Cisplatin-based combination chemotherapy in the treatment of poorly
      differentiated carcinoma and poorly differentiated adenocarcinoma of unknown
      primary site: results of a 12-year experience.
AB  - PURPOSE: We previously reported excellent responses to cisplatin-based
      chemotherapy in a minority of patients with poorly differentiated carcinoma (PDC)
      or poorly differentiated adenocarcinoma (PDA) of unknown primary site. We have
      continued to study and to treat these patients, and now report clinical
      characteristics, treatment results, and prognostic factors in a large group of
      patients identified prospectively. PATIENTS AND METHODS: Between February 1978
      and December 1989, we treated 220 patients with PDC or PDA of unknown primary
      site. The median age was 39 years; 48% of patients had predominant tumor location
      in the mediastinum, retroperitoneum, or peripheral lymph nodes. Specialized
      pathologic studies resulted in the identification of specific tumor types in only
      a few cases. All patients received cisplatin-based chemotherapy; between 1978 and
      1984, 116 patients received cisplatin, vinblastine, and bleomycin (PVeB) +/-
      doxorubicin, and 104 patients treated since January 1985 received cisplatin and
      etoposide +/- bleomycin. RESULTS: One hundred thirty-eight patients (63%) had
      objective responses to therapy, and 58 (26%) had complete response. Thirty-six
      patients (16%) are currently disease-free at a median of 61 months following
      therapy (range, 11 to 142 months). Actuarial 10-year survival is 16%. Favorable
      prognostic factors identified by Cox regression analysis include: (1) predominant
      tumor location in the retroperitoneum or peripheral lymph nodes, (2) tumor
      limited to one or two metastatic sites, (3) no history of cigarette use, and (4)
      younger age. CONCLUSION: Patients with PDC or PDA of unknown primary site
      represent another group of patients for whom potentially curative therapy is
      available. Patients with this syndrome should be distinguished from patients with
      well-differentiated adenocarcinoma of unknown primary site, and should receive a
      trial of cisplatin-based chemotherapy.

PMID- 1375285
TI  - Vasoactive intestinal polypeptide modulates GABAA receptor function in bipolar
      cells and ganglion cells of the rat retina.
AB  - 1. The effect of vasoactive intestinal polypeptide (VIP) on bipolar cells and
      ganglion cells freshly dissociated from the rat retina was studied under voltage
      clamp with the use of patch-clamp recording in the whole-cell configuration. 2.
      Application of VIP (1-100 microM) by itself resulted in no detectable current
      response in either bipolar cells or ganglion cells. However, gamma-aminobutyric
      acid (GABA)-activated macroscopic current responses elicited in both neuronal
      populations were potentiated on superimposed exposure to the neuropeptide. 3.
      GABA-activated chloride currents and muscimol-induced current responses were
      similarly potentiated on exposure to VIP, suggesting a synergistic interaction
      between VIP and GABAA receptor mechanisms. 4. We postulate that VIP plays a
      neuromodulatory role by regulating the excitability of inner retinal neurons and
      in this way modulates the efficacy of synaptic transmission in the retina.

PMID- 1375286
TI  - Mesencephalotomy for cancer pain.

PMID- 1375288
TI  - The magnitude of the acute phase protein response is attenuated by protein
      deficiency in rats.
AB  - We assessed the growth rate and changes in plasma albumin, total protein and
      alpha 2-macroglobulin concentrations (a major acute phase protein in rats) before
      and after a subcutaneous injection of turpentine (0.5 mg/kg body wt) in groups of
      rats receiving one of a series of protein-deficient diets (protein concentrations
      of 0.5, 1.5, 3.0, 4.5 or 6.0 g/100 g) or a diet containing an adequate level of
      protein (20 g/100 g) for maximal growth. Increasing protein deficiency in the
      different groups of animals reduced the basal albumin and total protein
      concentrations and attenuated the total protein and alpha 2-macroglobulin
      responses to turpentine. Increasing protein deficiency delayed the time taken for
      alpha 2-macroglobulin to reach peak concentrations post-injection and its return
      to basal concentrations. The turpentine-induced hypoalbuminemia was similar in
      all groups of animals (approximately 10 g/L depression) but restoration to values
      that were present before turpentine injection was increasingly delayed with
      increasing protein deficiency. The magnitude of the acute phase response (peak
      alpha 2-macroglobulin concentration) was found to be directly related to growth
      rate (r = 0.70, P less than 0.001). We concluded that protein deficiency can
      alter the pattern and magnitude of the acute phase responses in circulating
      protein concentrations to an extent that is dependent on the severity of protein
      deficiency.

PMID- 1375287
TI  - Porcine colostrum and milk stimulate visceral organ and skeletal muscle protein
      synthesis in neonatal piglets.
AB  - Our objective was to determine the relative contributions of protein synthesis
      and protein absorption in the rapid accretion of gastrointestinal protein in
      suckling piglets during the early neonatal period. We measured the rates of
      tissue protein synthesis using a flooding dose of L-[4-3H]phenylalanine in
      various visceral and peripheral tissues of neonatal piglets fed water, mature
      milk or colostrum for 6 h. The jejunal and ileal protein synthesis rates in
      piglets fed either colostrum or milk were three- to fourfold higher than in
      piglets fed water. The increased jejunal and ileal protein synthesis could not,
      however, account for the differences in protein mass between the colostrum-fed
      and water-fed groups. The relative abundance of IgG, a major porcine colostral
      protein, in jejunal tissue was markedly higher in piglets fed colostrum than in
      piglets fed either milk or water. The fractional protein synthesis rates in
      liver, kidney, spleen and skeletal muscle and the absolute protein synthesis
      rates in liver and spleen were also greater in piglets fed colostrum than in
      those fed milk or water. Increased endogenous protein synthesis made only a minor
      contribution to the increased intestinal protein accretion in neonatal piglets
      fed colostrum. A much larger proportion of this increase seemed to be a result of
      absorption and retention of ingested immunoglobulins.

PMID- 1375289
TI  - Rubeotic glaucoma and retinopathy of prematurity: a case report.

PMID- 1375290
TI  - B-cell epitope mapping of the entire SIVagm envelope glycoprotein including fine
      mapping of immunogenic regions.
AB  - To allow the precise definition of the anti-lentiviral immune response in the
      natural host and to facilitate the development of an alternative animal model for
      vaccine development, we are identifying the immunogenic domains of SIVagm
      proteins. First, a total of 173 synthetic 15-mer peptides with an overlap of 10
      amino acids were produced spanning the entire envelope glycoprotein of the
      molecular clone SIVagm3. These peptides were used as antigen in enzyme-linked
      immunosorbent assays for identifying regions recognized by antibodies from
      naturally infected African green monkeys and monkeys infected with a molecular
      clone. Regions corresponding to the HIV-1 V3, the transmembrane protein (TMP)
      "Gnann peptide", and the C-terminal area of the outer envelope protein were shown
      to be immunodominant. These regions were re-synthesized as 15-mer peptides with
      an overlap of 14 amino acids and used to precisely map the epitopes recognized.
      Sera from 93 captive and 61 wild animals were tested by SIVagm-specific Western
      blot (WB) and for ELISA reactivity against the immunodominant TMP peptide. One
      hundred percent (76/76) of the WB-positive captive animals and 98% (41/42) wild
      WB-positive animals also reacted against the peptide. In contrast, only 62% of
      the WB-positive sera reacted with the "V3" epitope and 46% with the gp130 C
      terminal epitope.

PMID- 1375291
TI  - CD20 expression is increased on B lymphocytes from HIV-infected individuals.
AB  - In studies presented here, we show that expression of the pan B cell marker CD20
      is markedly increased on B lymphocytes from HIV-infected individuals and that
      this increase tends to be greater in individuals with more advanced disease. By
      using multiparameter FACS analyses to quantitate surface density of CD20 and
      intracellular glutathione (GSH) levels simultaneously, we further show that the
      distribution of intracellular glutathione (GSH) levels in B cells of HIV-infected
      individuals is more heterogeneous than in uninfected controls. Finally, we show
      that the intracellular GSH levels correlate with CD20 expression on a per-cell
      basis in all infected individuals. These findings suggest that CD20 expression,
      which can be precisely measured, may prove to be a useful surrogate marker for
      monitoring HIV infection.

PMID- 1375292
TI  - Urticaria: new molecular insights and treatments. The Parkes Weber Lecture 1991.
AB  - Chronic urticaria remains one of the major unsolved clinical problems in
      dermatology. My group has employed an integrated experimental approach in order
      to shed light on the pathophysiology and treatment of this group of disorders.
      Using delayed pressure urticaria as a model, evidence has emerged of the role of
      eosinophil major basic protein (MBP) and of interleukin-6 (IL-6) as important
      molecular mediators, possibly explaining the poor response to H1 antihistamines.
      Our recent work in chronic idiopathic urticaria has led to identification of a
      circulating greater than 100 kD factor which causes wealing following intradermal
      injection and which releases histamine from normal leukocytes in vitro. Further
      characterisation confirmed that this skin and histamine releasing reactivity is
      due mainly to an IgG anti-IgE autoantibody. That this autoantibody is
      functionally significant is supported not only by its ability to release
      histamine and cause local wealing, but also by the results of removal by
      plasmapheresis which we have shown to cause clinical improvement in seven out of
      eight patients with severe unremitting chronic urticaria. It is concluded that
      chronic 'idiopathic' urticaria is an autoimmune disease due, in most patients, to
      a functionally significant IgG anti-IgE autoantibody. Immunotherapy offers the
      best long-term prospects of relief in severe unremitting cases.

PMID- 1375293
TI  - Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 2. Tricyclic
      pyridobenzoxazepinones and dibenzoxazepinones.
AB  - Dibenz[b,f][1,4]oxazepin-11(10H)-ones (III), pyrido[2,3-b][1,4]benzoxazepin-6(5H)
      ones (IV), and pyrido[2,3-b]- [1,5]benzoxazepin-5(6H)-ones (V) were found to
      inhibit human immunodeficiency virus type 1 reverse transcriptase with IC50
      values as low as 19 nM. A-ring substitution has a profound effect on activity,
      with appropriate substituents at the positions ortho and para to the lactam
      nitrogen providing dramatically enhanced potency. Substitution in the C-ring is
      generally neutral or detrimental to activity. Although a C-ring amino substituent
      at the position meta to the lactam carbonyl is generally beneficial to activity,
      it has essentially no effect when the A-ring is optimally substituted. Like the
      dipyridodiazepinone nevirapine, compounds III-V are specific for HIV-1 RT,
      exhibiting no inhibitory activity against HIV-2 RT or other virial reverse
      transcriptase enzymes.

PMID- 1375294
TI  - Modulation of transcription in rat liver nuclei in vitro by a diol epoxide of
      benzo[a]pyrene.
AB  - Treatment of isolated rat liver nuclei with 7 beta, 8 alpha-dihydroxy-9 alpha, 10
      alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene, the ultimate carcinogenic
      metabolite of benzo[a]pyrene, resulted in inhibition of transcription as measured
      by radioactive precursor incorporation into RNA. The mechanism of inhibition as
      analyzed by use of different types of inhibitors suggested that the carcinogen
      acted on both the major components of transcription machinery, that is, the
      template chromatin and the enzyme RNA polymerases. This action correlates well
      with the observations made after administration of benzo[a]pyrene to rats.

PMID- 1375295
TI  - Renal excretion of perfluorooctanoic acid in male rats: inhibitory effect of
      testosterone.
AB  - There is a marked sex difference in the whole-body elimination of
      perfluorooctanoic acid (PFOA) in rats, with females excreting the perfluorinated
      acid much more rapidly (half life [t1/2] less than 1 day) than males (t1/2 = 15
      days). Our objective was to determine if androgens or estrogens are involved in
      causing this sex difference in PFOA elimination. Castration of males greatly
      increased the elimination of [1-14C]PFOA (9.4 mumol/kg, i.p.) in urine,
      demonstrating that a factor produced by the testis was responsible for the slow
      elimination of PFOA in male rats. Castration plus 17 beta-estradiol had no
      further effect on PFOA elimination whereas castration plus testosterone
      replacement at the physiologic level reduced PFOA elimination to the same level
      as rats with intact testes. Thus, in male rats, testosterone exerts an inhibitory
      effect on renal excretion of PFOA. In female rats, neither ovariectomy nor
      ovariectomy plus testosterone affected the PFOA urinary elimination,
      demonstrating that the inhibitory effect of testosterone on PFOA renal excretion
      is a male-specific response. Probenecid decreased the high rate of PFOA renal
      excretion in castrated males but had no effect on male rats with intact testes.
      We conclude that testosterone is a key determinant of the sex difference in PFOA
      elimination in rats.

PMID- 1375296
TI  - Fine structure of the dorsal lingual epithelium of the little tern, Sterna
      albifrons Pallas (Aves, Lari).
AB  - The dorsal surface of the tongue of the little tern, Sterna albifrons, has a
      distinctive anterior region for five-sixths of its length and a terminal
      posterior region. The anterior region observed by scanning electron microscopy is
      distinguished along its forward half by a median line from which median papillae
      protrude. The hind half of the anterior region has a median sulcus without
      papillae. The deciduous epithelium on both sides of the median line and sulcus
      bears scattered epithelial protrusions. The posterior lingual region has neither
      median papillae nor deciduous epithelium. So-called giant conical papillae are
      located in a transverse row between anterior and posterior regions. Delicate
      microridges adorn the surfaces of all outer epithelial cells in both regions.
      Examination of the dorsal lingual epithelium by light and electron microscopy
      provides histologic and cytologic criteria for distinguishing anterior and
      posterior regions. Basal cells are nearly alike throughout the dorsal epithelium.
      Intermediate layer cells of the anterior region contain numerous tonofibrils in
      electron-dense bundles composed of 10 nm tonofilaments. The outer layer is
      composed of electron-dense, well-keratinized cells, and electron-lucent
      epithelial protrusions are present on the exposed surface of the outermost cells.
      Median papillae are composed of typical keratinized cells, which are nearly
      filled with keratin filaments. Intermediate layer cells in the posterior region
      of the tongue are nearly filled with unbundled tonofilaments. There is only a
      very thin outer keratinized layer in this region.

PMID- 1375297
TI  - Teratogenic and macromolecular synthesis inhibitory effects of trimethylamine on
      mouse embryos in culture.
AB  - Trimethylamine (TMA) is an aliphatic amine, and its blood levels can increase
      after ingestion of certain foods, such as fish, and during disease states, such
      as chronic renal failure. We recently reported that TMA can inhibit fetal
      development in vivo and in vitro in mice. The present studies were done to find
      out if the inhibitory effects of TMA on embryonic development are caused by a
      decrease in macromolecular synthesis, using mouse embryo cultures as the
      experimental model. At a submaximally toxic concentration (0.75mM), TMA inhibited
      the growth of embryos to approximately 70% of control and caused neural-tube
      defects in 73% of embryos. By 42 h of culture, DNA, RNA, and protein content of
      TMA-treated embryos were approximately 50% of the control values. Embryotoxic
      effects of TMA were not caused by changes in pH and osmolarity of the culture
      media. The inhibitory effects of TMA on embryonic growth were time dependent and
      apparent at 2-4 h of culture. The inhibition of growth was accompanied by a
      decrease in the incorporation of tritium-labeled thymidine, uridine, and leucine
      into DNA, RNA, and proteins, respectively. Thiols (L- and D-cysteine,
      glutathione) and the antioxidant L-ascorbic acid did not cause significant
      antagonism of embryotoxic effects of TMA. It is concluded that TMA exerts
      teratogenic effects on mouse embryos in culture and inhibits their growth by
      reducing macromolecular synthesis; these effects may not involve glutathione
      depletion or generation of free radicals.

PMID- 1375298
TI  - Partially hepatectomized rats: a model for the study of the effect of toxins on
      the plasma protein profiles of nascent hepatocytes.
AB  - A useful framework is proposed for unifying the synthesis of plasma proteins and
      their degradation by, or release from, liver cells of intact and partially
      hepatectomized rats, in which synthesis and release of acute-phase plasma
      proteins occur in synchrony with the internalization and catabolism of plasma and
      extracellular proteins. The catabolism of proteins and other hepato-intracellular
      glycoproteins during sepsis or trauma is essential to provide constituent amino
      acids and carbohydrates for the synthesis of acute-phase plasma proteins.
      Increases in the plasma levels of acute-phase response proteins in sham-operated
      rats reached a maximum between 1 and 2 d after mock surgery, and had returned
      virtually to control levels within 6 d. By contrast, acute-phase proteins in the
      plasma of partially hepatectomized rats were decreased by 10-20% of their initial
      values after 24 h. A maximum acute-phase response on d 7 after the operation was
      characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein,
      hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below
      control levels, for example, by 11, 25, and 38% for albumin, transferrin, and
      prealbumin, respectively. This delayed response suggests that the nascent liver
      cells had inherited the capacity of the parent cells to respond to inflammatory
      signal and had synthesized acute-phase plasma proteins. Accordingly, a time frame
      for the application of toxin to nascent hepatocytes is suggested. An increased
      activity (300 +/- 50%) for both bound and free neuraminidase in remnant liver
      tissue 19 h post partial hepatectomy suggested that hepatic regenerating
      factor(s) were produced in liver tissue via the hepatic bound and/or free
      neuraminidase-mediated desialylation of humoral substrates. By contrast,
      circulating levels of lysosomal enzymes alpha-fucosidase and beta-N-acetyl-D
      glucosaminidase were increased marginally after 24 h but had returned nearly to
      control levels after 7 d, suggesting that lysosomal acid hydrolases do not play a
      major role in regenerative DNA synthesis, mitosis, or in the synthesis of acute
      phase plasma proteins.

PMID- 1375299
TI  - [Histopathological characteristics of rheumatoid arthritis--as a clue to
      elucidate its pathogenesis].
AB  - A correct histopathological diagnosis of Rheumatoid Arthritis (RA) is quite
      important for the decision of early phase treatment to cure it fundamentally.
      But, generally speaking, usual hospital pathologist is not so much experienced
      about RA. The purpose of this article is originally to let such pathologist
      familiar in RA pathology, but for the RA specialist to offer any clue to
      elucidate the still-unknown etio-pathogenesis of RA or to cure RA fundamentally.
      The "Tetralogy of RA Arthritis for pathologist" must be as follows: (1) Enormous
      proliferation of well-permeable granulation-tissue-type neo-vascularization, some
      of which became high column-endothelial and the center of primary as well as
      secondary follicle-like lymphoid cell cluster. (2) Lymphoid cluster in RA
      synovium is also pathological in function. It consisted of preferentially CD4T
      and B cells to produce IgG rheumatoid factor endlessly. (3) Synovial lining A and
      B cells proliferate as far as five layers of each, but later, the sublining D (M)
      and D (F) cells proliferate more and more and finally replace the lining cells. D
      (M) cells express macrophage marker and full of lysosome, on the contrary, D (F)
      cells express mesenchymal marker and contains much metalloproteinase. Both
      express strong Class II antigens but neither has complement activation inhibitor
      DAF. (4) Proliferation of these D cells with full of mesenchymal tissue
      destroying and inflammation accelerating activity must be playing a major role in
      the joint destruction of RA, some in shape of pannus and more in shape of
      granulation tissue in and around the bone.

PMID- 1375300
TI  - [Effects of FK506 on aminonucleoside-induced nephrotic rats].
AB  - We examined the effect of immunosuppressive agent, FK506 (Fujisawa, Co.), on
      puromycin aminonucleoside (PAN)-induced nephrosis. Single i.p. injection of PAN
      in a dose of 100 mg/kg was introduced into Munich-Wistar rats weighing about 200
      g. Those rats were divided into four groups. PAN-induced nephrosis rats in group
      1 (PAN-FK0.1, n = 5), group 2 (PAN-FK0.3, n = 5), group 3 (PAN-FK1.0, n = 5) were
      treated with i.m. injection of FK506 for 10 days in a dose of 0.1 mg/kg, 0.3
      mg/kg, 1.0 mg/kg, respectively, and rats in group 4 were treated with FK-placebo
      (PAN-PL, n = 5). The rats in group 5 with Saline+placebo were served as a control
      (NS-PL, n = 5). Among 5 groups, urinary protein, anionic sites (AS) in GBM, and
      subsets of peripheral lymphocytes through FACS were compared. After 9 days of PAN
      injection, the rats in PAN-FK0.1 (160.0 +/- 38.4), PAN-FK0.3 (118.0 +/- 34.4) &
      PAN-FK1.0 (89.2 +/- 40.0) given FK-506 had significantly less proteinuria in a
      PAN dose dependent manner, compared to those in NS-PL (349 +/- 86.8 mg/day). The
      numbers of AS/1000 mmGBM were more attenuated in FK506-treated PAN rats (PAN
      FK1.0; 16.2 +/- 3.9) than those in PAN-PL (11.7 +/- 4.4). In related to subset of
      lymphocytes, increased W3/25 in PAN-PL was regressed in PAN-FK0.1, PAN-FK0.3 &
      PAN-1.0 after 10 days of PAN-injection. W3/25/OX-8 was significantly higher in
      PAN-PL (3.6) than those in NS-PL (2.4), but not between PAN-1.0 & NS-PL. These
      data indicate that the mechanism for therapeutic effect of FK506 on PAN-induced
      nephrosis includes a revision of abnormal cellular immunity, which attenuates the
      decrease of AS structure and as a result decrease proteinuria.

PMID- 1375301
TI  - Flow cytometric detection of rare normal human marrow cells with immunophenotypes
      characteristic of acute lymphoblastic leukemia cells.
AB  - Rare subpopulations of normal marrow B lymphoid cells expressing immunophenotypes
      typically found in B-lineage acute lymphoblastic leukaemias (ALL) were sought by
      multiparameter flow cytometry. First, CD34+ marrow leukocytes were isolated by
      immune adherence using immunomagnetic microspheres, and analyzed for coexpression
      of the following pairs of membrane antigens: CD34 CD22; CD34 CD20; and CD10 CD22.
      Terminal deoxynucleotidyl transferase expression was not assessed. All three
      antigen combinations were found on small percentages of the CD34-enriched cell
      population. Second, unseparated normal low density marrow leukocytes were
      examined by 'gating' on cells with the right-angle light scatter of lymphoid
      cells, plus either CD34+ or CD10+ immunofluorescence. This independent approach
      confirmed that rare subsets of normal cells coexpress 'immature' and 'mature'
      differentiation antigens. In addition, remission marrow cells were examined from
      two children who had completed therapy for ALL two and four months earlier. Both
      specimens had a more than threefold increase in CD34+ cells over normal marrow,
      and cells coexpressing immature and mature cell surface antigens were easily
      detected. These findings demonstrate that immunophenotypes characteristic of B
      lineage ALL, previously labeled 'asynchronous' with respect to the developmental
      sequence of the majority of normal B lymphoid cells, exist at low frequency in
      normal human bone marrow.

PMID- 1375302
TI  - Expression of surface adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3) in adult
      acute leukemia: relationship with initial characteristics and prognosis.
AB  - Adhesion molecules CD58 and CD54 are involved in cell-cell interactions that are
      potentially important in the biology of acute leukemia (AL). Expression of these
      molecules was studied in 79 cases of adult AL including 50 cases of acute non
      lymphoid leukemia (ANLL) and 29 cases of acute lymphoid leukemia (ALL) using an
      indirect immunofluorescence technique. CD58 was expressed in 45 +/- 26% of ANLL
      cells and 43 +/- 32% of ALL cells, and its expression did not correlate with any
      other marker. In ALL, the expression of CD58 was inversely correlated with the
      presence of a clinical tumoral syndrome (p = 0.0009), leucocytosis (p = 0.005),
      and the percent of peripheral blast cells (p = 0.001). The major finding in this
      study was the association between CD58 expression and prognosis. In ANLL, higher
      expression of CD58 was independently associated with higher CR rate (p = 0.04),
      longer overall survival (p = 0.02), and longer disease-free survival (p = 0.007).
      In ALL, higher expression of CD58 was associated with longer survival (p = 0.05).
      CD54 was expressed only on 17 +/- 16% of ANLL cells and 11 +/- 11% of ALL cells;
      its expression on ANLL was positively correlated with that of CD11 (p = 0.03),
      CD15 (p = 0.001) and CD34 (p = 0.01). CD54 expression did not correlate with
      clinical and hematologic characteristics. We conclude that the expression of
      adhesion molecule CD58, but not CD54, in AL is related to initial characteristics
      and evolution of the disease.

PMID- 1375303
TI  - CD5+ B cells from bovine leukemia virus infected cows are activated cycling cells
      responsive to interleukin 2.
AB  - Most of the B cells from bovine leukemia virus (BLV) infected cows in persistent
      lymphocytosis (PL) were known to express the CD5 T-cell marker but it was not
      known whether this peculiar membrane phenotype relates to an activation state. It
      was demonstrated that these B cells were also flagged by two other membrane
      markers normally borne by cells belonging to the myeloid lineage (namely CD11b
      and CD11c). Moreover, cell cycle analysis illustrated that a significant
      percentage of these B cells (greater than 15%) left their resting (G0/G1) status
      and progressed through the cell cycle. In addition, T-cell-depleted peripheral
      blood mononuclear cells from animals in PL were shown to proliferate in response
      to a IL-2-containing supernatant (MLA 144). These results indicate that the CD5+
      B cells from BLV-infected cows in PL are activated cells.

PMID- 1375304
TI  - Recombinant human TNF-alpha stimulates the secretion of granulocyte colony
      stimulating factor in vivo.
AB  - Tumor necrosis factor (TNF) is a macrophage-derived cytokine that causes
      hemorrhagic necrosis of several human tumors in vitro. It has a wide range of
      biologic effects including stimulation of secretion of both granulocyte colony
      stimulating factor (G-CSF) and granulocyte/macrophage colony-stimulating factor
      (GM-CSF) by normal adult lung fibroblasts in culture. No in vivo data are
      available on the effect of exogenously administered TNF on cytokine production.
      In the studies reported here, we show that G-CSF accumulates in the serum in vivo
      in response to recombinant TNF (rTNF) administration. At the peak of the response
      circulating levels of 2-6 ng/ml of biologically active G-CSF are detectable.
      Surprisingly, circulating levels of GM-CSF, interleukin-3 as well as a number of
      other cytokines were not detectable within the limits of the assays. The results
      indicate that the levels of GM-CSF or interleukin-3 are minimally 100-fold lower
      than the peak levels of G-CSF. These data illustrate the complex interplay that
      cytokines have in vivo. Understanding these interactions in humans is crucial to
      the correct use of this new class of agents in the clinic.

PMID- 1375305
TI  - Sensitivity and specificity of five different mycoplasma detection assays.
AB  - The sensitivity and specificity of five different mycoplasma detection tests were
      evaluated in comparison with the classical microbiological culture assay on agar
      plates as the reference method: direct fluorochrome DNA staining (direct DAPI),
      DNA staining of an indicator cell line (indirect DAPI), RNA hybridization with a
      cDNA specific for ribosomal mycoplasmal RNA, an enzyme-linked immunosorbent assay
      (ELISA) with mycoplasma-specific antibodies, and a biochemical cytotoxicity assay
      (6-MPDR). A large panel of continuous cell lines (20 adherent and 233 suspension
      cell lines, most of the latter were human leukemia-lymphoma cell lines) were
      analyzed for infection with mycoplasma. The results of the comparative analysis
      for sensitivity and specificity of the various tests were as follows: 100% and
      100% for the indirect DAPI, 100% and 98% for the RNA hybridization assay, 87% and
      94% for the direct DAPI, 72% and 100% for the ELISA, 75% and 90% for the
      biochemical 6-MPDR assay. Each of these approaches has both advantages and
      disadvantages with regard to cost, time, reliability, specificity, and
      sensitivity. The best compromise for routine mycoplasma testing is a combination
      of several techniques (e.g. direct culture on agar, RNA hybridization, and direct
      or indirect DAPI).

PMID- 1375306
TI  - Effect of fluoxetine on serotonin and dopamine concentration in microdialysis
      fluid from rat striatum.
AB  - Fluoxetine injected i.p. into rats at a dose of 10 mg/kg rapidly increased
      serotonin concentration in microdialysis fluid from the striatum by at least 4
      fold, an increase that was maintained throughout the 3 hr observation period.
      Dopamine concentration in the microdialysis fluid did not change. The
      concentration of the two dopamine metabolites, 3,4-dihydroxyphenylacetic acid and
      homovanillic acid, was not changed in the microdialysis fluid, whereas the
      concentration of the serotonin metabolite, 5-hydroxyindoleacetic acid, was
      significantly decreased after fluoxetine injection. The increased extracellular
      concentration of serotonin no doubt resulted from inhibition of the serotonin
      uptake carrier by fluoxetine, and the lack of change in dopamine is evidence for
      the specificity of action of this uptake inhibitor.

PMID- 1375307
TI  - Osmotic complications of low-molecular-weight dextran therapy in free flap
      surgery.
AB  - Low-molecular-weight dextran is utilized by many microsurgeons after free tissue
      transfer for its beneficial effects on the microcirculation. While it is
      generally felt to have a low rate of complications, severe complications
      secondary to dextran's osmotic effects may occur. We report here on two cases in
      which therapy with low-molecular-weight dextran was strongly implicated as a
      causative factor in major complications. These cases and their background are
      reviewed. Guidelines for the safe administration of this agent in patients post
      free-tissue transfer are discussed.

PMID- 1375308
TI  - Histochemical discrimination of fibers in regenerating rat infraorbital nerve.
AB  - In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and
      cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes
      are CA positive and CE negative, whereas motor processes are CA negative and CE
      positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw
      extensive CA staining of nearly 100% of the myelinated axons. Although CE
      reactivity in myelinated axons was extremely rare, we did observe CE staining of
      unmyelinated autonomic fibers. Four weeks after transection of infraorbital
      nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3
      distinct morphological zones. A fraction of the viable axons retained CA activity
      to within 2 mm of the distal extent of the stump, and the stain is capable of
      resolving growth sprouts being regenerated from these fibers. Staining of
      unmyelinated autonomic fibers in serial sections shows that CE activity was not
      retained as far distally as is the CA sensory staining.

PMID- 1375309
TI  - The influence of ribosome-binding-site elements on translational efficiency in
      Bacillus subtilis and Escherichia coli in vivo.
AB  - A method is described to determine simultaneously the effect of any changes in
      the ribosome-binding site (RBS) of mRNA on translational efficiency in Bacillus
      subtilis and Escherichia coli in vivo. The approach was used to analyse
      systematically the influence of spacing between the Shine-Dalgarno sequence and
      the initiation codon, the three different initiation codons, and RBS secondary
      structure on translational yields in the two organisms. Both B. subtilis and E.
      coli exhibited similar spacing optima of 7-9 nucleotides. However, B. subtilis
      translated messages with spacings shorter than optimal much less efficiently than
      E. coli. In both organisms, AUG was the preferred initiation codon by two- to
      threefold. In E. coli GUG was slightly better than UUG while in B. subtilis UUG
      was better than GUG. The degree of emphasis placed on initiation codon type, as
      measured by translational yield, was dependent on the strength of the Shine
      Dalgarno interaction in both organisms. B. subtilis was also much less able to
      tolerate secondary structure in the RBS than E. coli. While significant
      differences were found between the two organisms in the effect of specific RBS
      elements on translation, other mRNA components in addition to those elements
      tested appear to be responsible, in part, for translational species specificity.
      The approach described provides a rapid and systematic means of elucidating such
      additional determinants.

PMID- 1375310
TI  - Translation initiation in Escherichia coli: sequences within the ribosome-binding
      site.
AB  - The translational roles of the Shine-Dalgarno sequence, the initiation codon, the
      space between them, and the second codon have been studied. The Shine-Dalgarno
      sequence UAAGGAGG initiated translation roughly four times more efficiently than
      did the shorter AAGGA sequence. Each Shine-Dalgarno sequence required a minimum
      distance to the initiation codon in order to drive translation; spacing, however,
      could be rather long. Initiation at AUG was more efficient than at GUG or UUG at
      each spacing examined; initiation at GUG was only slightly better than UUG.
      Translation was also affected by residues 3' to the initiation codon. The second
      codon can influence the rate of initiation, with the magnitude depending on the
      initiation codon. The data are consistent with a simple kinetic model in which a
      variety of rate constants contribute to the process of translation initiation.

PMID- 1375311
TI  - The binding of Cellulomonas fimi endoglucanase C (CenC) to cellulose and Sephadex
      is mediated by the N-terminal repeats.
AB  - Endoglucanase C (CenC) from Cellulomonas fimi binds to cellulose and to Sephadex.
      The enzyme has two contiguous 150-amino-acid repeats (N1 and N2) at its N
      terminus and two unrelated contiguous 100-amino-acid repeats (C1 and C2) at its C
      terminus. Polypeptides corresponding to N1, N1N2, C1, and C1C2 were produced by
      expression of appropriate cenC gene fragments in Escherichia coli. N1N2, but not
      N1 alone, binds to Sephadex; both polypeptides bind to Avicel, (a heterogeneous
      cellulose preparation containing both crystalline and non-crystalline
      components). Neither C1 nor C1C2 binds to Avicel or Sephadex. N1N2 and N1 bind to
      regenerated ('amorphous') cellulose but not to bacterial crystalline cellulose;
      the cellulose-binding domain of C. fimi exoglucanase Cex binds to both of these
      forms of cellulose. Amino acid sequence comparison reveals that N1 and N2 are
      distantly related to the cellulose-binding domains of Cex and C. fimi
      endoglucanases A and B.

PMID- 1375312
TI  - Effect of galanin on growth hormone-releasing hormone-stimulated growth hormone
      secretion in adult patients with nonendocrine diseases on long-term daily
      glucocorticoid treatment.
AB  - Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an
      enhancement of endogenous somatostatin tone. The aim of our study was to evaluate
      the effect of galanin, a neuropeptide that stimulates GH secretion, on GH
      releasing hormone (GHRH)-induced GH secretion in adult patients with nonendocrine
      diseases who were under daily immunosuppressive glucocorticoid therapy. Six
      normal subjects (four men, two women) and seven steroid-treated subjects (three
      men, four women) were studied. GHRH-induced GH secretion was evaluated during a
      40-minute intravenous (i.v.) infusion of saline or porcine galanin (12.5
      micrograms/min). During saline infusion, steroid-treated patients showed a
      blunted GH response to GHRH (GH peak, 8.1 +/- 2.8 micrograms/L), as compared with
      normal subjects (GH peak, 23.8 +/- 3.9 micrograms/L). During galanin infusion,
      the GH response to GHRH was significantly enhanced (GH peak, 46.6 +/- 9.4
      micrograms/L, P less than .05), as compared with saline infusion in normal
      subjects. In contrast, galanin infusion did not enhance the GH response to GHRH
      (GH peak, 16.6 +/- 6.5 micrograms/L), as compared with saline infusion in steroid
      treated patients. The area under the GH-response curves was also significantly (P
      less than .05) lower in steroid-treated subjects, as compared with normal
      subjects. Thus, galanin failed to normalize or enhance the GH response to GHRH in
      patients treated long-term with glucocorticoids. It can be hypothesized that
      galanin does not elicit GH secretion by decreasing hypothalamic somatostatin
      tone.

PMID- 1375313
TI  - Glyphosate selected amplification of the 5-enolpyruvylshikimate-3-phosphate
      synthase gene in cultured carrot cells.
AB  - CAR and C1, two carrot (Daucus carota L.) suspension cultures of different
      genotypes, were subjected to stepwise selection for tolerance to the herbicide
      glyphosate [(N-phosphonomethyl)glycine]. The specific activity of the target
      enzyme, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), as well as the mRNA
      level and copy number of the structural gene increased with each glyphosate
      selection step. Therefore, the tolerance to glyphosate is due to stepwise
      amplification of the EPSPS genes. During the amplification process, DNA
      rearrangement did not occur within the EPSPS gene of the CAR cell line but did
      occur during the selection step from 28 to 35 mM glyphosate for the C1 cell line,
      as determined by Southern hybridization of selected cell DNA following EcoRI
      restriction endonuclease digestion. Two cell lines derived from a previously
      selected glyphosate-tolerant cell line (PR), which also had undergone EPSPS gene
      amplification but have been maintained in glyphosate-free medium for 2 and 5
      years, have lost 36 and 100% of the increased EPSPS activity, respectively.
      Southern blot analysis of these lines confirms that the amplified DNA is
      relatively stable in the absence of selection. These studies demonstrate that
      stepwise selection for glyphosate resistance reproducibly produces stepwise
      amplification of the EPSPS genes. The relative stability of this amplification
      indicates that the amplified genes are not extrachromosomal.

PMID- 1375314
TI  - Regulation and interaction of multiple protein factors with the proximal promoter
      regions of a rice high pI alpha-amylase gene.
AB  - The alpha-amylase gene is known to be regulated by the plant hormone gibberellin
      (GA) in cereal aleurone cells. The accumulation of the mRNA corresponding to a
      rice high pI alpha-amylase gene, OSamy-c, was stimulated 20-fold by exogenous GA3
      in half-seeds lacking embryos. Regulatory regions in the promoter of this high pI
      sub-family were analyzed. The OSamy-c 5' flanking sequence, spanning positions 
      231 to +29, was fused upstream of the beta-glucuronidase (GUS) gene coding
      region. The delivery of this plasmid into rice aleurone cells by the biolistic
      method resulted in a GA-stimulated synthesis of GUS. Gel retardation assays were
      performed to study protein-DNA interactions between putative regulatory sequences
      of OSamy-c and partially purified rice seed extracts. We identified multiple seed
      specific protein factors that bind to proximal regions of the OSamy-c promoter
      between positions -231 and -162. Five different proteins were distinguished based
      on competitive binding studies. Three protein binding regions were located by
      footprinting analyses, one of which is located in the conserved sequence also
      found upstream of other GA-inducible genes. Two protein factors in rice aleurone
      cells that interact with the putative regulatory sequence do not require GA
      induction.

PMID- 1375315
TI  - Multiple states of rat brain (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid receptors as revealed by quantitative autoradiography.
AB  - The binding of (RS)-alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      ([3H]AMPA), a selective ligand for non-N-methyl-D-aspartate excitatory amino acid
      receptors, was investigated in rat brain using an autoradiographic receptor
      binding technique. [3H]AMPA binding sites were widely distributed throughout the
      rat central nervous system, and the rank order of potency of displacers of
      [3H]AMPA binding was quisqualate greater than AMPA greater than 6,7
      dinitroquinoxaline-2,3-dione = 6-cyano-7-nitroquinoxaline-2,3-dione greater than
      beta-N-oxalylamino-L-alanine greater than glutamate greater than kainate.
      Potassium thiocyanate (0-100 mM) exerted a 4-fold stimulation of [3H]AMPA
      binding, without changing the relative regional distribution of [3H]AMPA binding
      densities among rat brain regions. Scatchard analysis of equilibrium saturation
      binding revealed high affinity and low affinity components of [3H]AMPA binding,
      even in the absence of potassium thiocyanate. Addition of potassium thiocyanate
      increased the number of high affinity [3H]AMPA binding sites without a change in
      affinity. In addition, the number of low affinity [3H]AMPA binding sites was
      unchanged in the presence of potassium thiocyanate, but the affinity of low
      affinity [3H]AMPA binding was greatly increased. [3H]AMPA thus binds specifically
      to two affinity conformations of postsynaptic binding sites that appear to be
      interconverted with potassium thiocyanate. The pharmacologic profile of these
      sites is consistent with that of the ion channel-linked ("ionotropic")
      quisqualate/AMPA class of excitatory amino acid receptor in the rat central
      nervous system.

PMID- 1375316
TI  - Stimulation of adenylate cyclase by amylin in CHO-K1 cells.
AB  - The CHO-K1 cell line responds to the peptide amylin by a rapid elevation of cAMP.
      The related peptide calcitonin gene-related peptide (CGRP) is 100 times less
      potent at stimulating adenylate cyclase than is amylin. The actions of amylin at
      this receptor are concentration dependent and not antagonized by the CGRP
      antagonist CGRP-(8-37). Although these cells have receptors for calcitonin,
      amylin is unable to take part in any high affinity interaction with these
      receptors, as assessed by radioligand binding. The CHO-K1 cell line has receptors
      for amylin that are distinct from those for calcitonin and CGRP.

PMID- 1375317
TI  - Kynurenic acid analogues with improved affinity and selectivity for the glycine
      site on the N-methyl-D-aspartate receptor from rat brain.
AB  - The glycine site on the N-methyl-D-aspartate (NMDA) subtype of receptors for the
      excitatory neurotransmitter glutamate is a potential target for the development
      of neuroprotective drugs. We report here two chemical series of glycine site
      antagonists derived from kynurenic acid (KYNA), with greatly improved potency and
      selectivity. Disubstitution with chlorine or bromine in the 5- and 7-positions of
      KYNA increased affinity for [3H]glycine binding sites in rat cortex/hippocampus
      P2 membranes, with a parallel increase of potency for antagonism of NMDA-evoked
      responses in the rat cortical wedge preparation. The optimal compound was 5-I,7
      Cl-KYNA, with an IC50 for [3H]glycine binding of 29 nM and an apparent Kb in the
      cortical wedge preparation of 0.41 microM. Reduction of the right-hand ring of
      5,7-diCl-KYNA reduced affinity by 10-fold, but this was restored by substitution
      in the 4-position with the trans-phenylamide and further improved in the trans
      benzylamide. The optimal compound was the transphenylurea (L-689,560), with an
      IC50 of 7.4 nM and an apparent Kb of 0.13 microM. Both series of compounds
      displayed a high degree of selectivity for the glycine site, having IC50 values
      of greater than 10 microM versus radioligand binding to the glutamate recognition
      sites of NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and
      kainate receptors and the strychnine-sensitive glycine receptor. Selectivity
      versus AMPA receptor-mediated responses was also apparent in the rat cortical
      wedge and in patch-clamp recordings of cortical neurons in culture. Experiments
      using [3H]dizocilpine (MK-801) binding indicated that 5,7-diBr-KYNA, 5,7-diCl
      KYNA, 5-I,7-Cl-KYNA, and L-689,560 all behaved as full antagonists and were
      competitive with glycine. Patch-clamp recordings of cortical neurons in culture
      also indicated that NMDA-induced currents were antagonized by competition for the
      glycine site, and gave no evidence for partial agonist activity. pKi values for
      5,7-diBr-KYNA and L-689,560 in these experiments were 7.2 and 7.98, respectively,
      similar to the affinities of these compounds in the glycine binding assay. The
      high affinity and selectivity of these new derivatives make them useful tools to
      investigate the function of the glycine site on the NMDA receptor.

PMID- 1375318
TI  - Characterization of the binding of [3H]L-689,560, an antagonist for the glycine
      site on the N-methyl-D-aspartate receptor, to rat brain membranes.
AB  - The binding characteristics of [3H]L-689,560 [(+/-)-4-(trans)-2-carboxy-5,7
      dichloro-4-phenylaminocarbonylamino -1,2,3,4- tetrahydroquinoline], a selective
      antagonist for the glycine site on the N-methyl-D-aspartate receptor, have been
      evaluated using rat cortex/hippocampus P2 membranes. Specific [3H]L-689,560
      binding was saturable, having a Kd of 2.97 nM and a Bmax of 4.15 pmol/mg of
      protein. The Bmax value was not significantly different from that obtained for
      [3H]glycine in the same membrane preparation, and L-689,560 and glycine were
      found to be mutually competitive. The specific binding of [3H]L-689,560 (1 nM)
      represented 96 +/- 0.02% (four experiments) of total binding. Association
      experiments at 4 degrees revealed that [3H]L-689,560 reached equilibrium in 120
      min, with a t1/2 of 40 min. The dissociation of [3H]L-689,560 was slow at 4
      degrees (t1/2 = 118 min), allowing the use of filtration to separate free from
      bound radioactivity. Both association and dissociation curves were best fitted by
      a double-exponential function, suggesting the presence of two components.
      Comparison of IC50 values obtained using [3H]glycine and [3H]L-689,560 binding
      for 21 glycine site ligands (including agonists, partial agonists, and
      antagonists, with affinities spanning 5 orders of magnitude) showed a 1:1
      correlation, with a correlation coefficient of 0.97. This suggests that efficacy
      does not have a large influence on the affinity of glycine site ligands when an
      agonist or antagonist radioligand is used. Ligands for other amino acid
      recognition sites did not directly inhibit [3H]L-689,560 binding. [3H]L-689,560
      is an improved radioligand for the glycine site that will facilitate further
      investigations of its properties.

PMID- 1375319
TI  - Nicotinic acetylcholine currents in cultured postnatal rat hippocampal neurons.
AB  - Nicotinic acetylcholine (ACh) currents were studied in cultured postnatal rat
      hippocampal neurons, using whole-cell voltage-clamp techniques. In most cells,
      ACh produces one of two types of response. One class of ACh currents exhibits
      rapid and profound desensitization and is sensitive to inhibition by alpha
      bungarotoxin (alpha BTXN). The second class activates slowly and exhibits no
      desensitization during prolonged agonist applications. This slow current is
      insensitive to alpha BTXN. Both the fast and slow responses exhibit inwardly
      rectifying current-voltage relationships and pass little current at positive
      membrane potentials. Both currents can be recorded in the presence of 1 microM
      atropine but are blocked by 0.1-1.0 mM d-tubocurarine and 0.1-1.0 mM
      mecamylamine. These observations suggest heterogeneity of nicotinic ACh receptors
      in rat hippocampal neurons and provide support for functional alpha BTXN
      sensitive nicotinic receptors in this region.

PMID- 1375320
TI  - Common features in the interaction of tetrahydroimidazo[4,5,1
      jk][1,4]benzodiazepin-2(1H)-one and -thione and 1-[(2-hydroxyethoxy)methyl]-6
      (phenylthio)thymine derivatives with the human immunodeficiency virus type 1
      reverse transcriptase.
AB  - Recently, several classes of compounds have been shown to be potent, selective,
      and specific inhibitors of human immunodeficiency virus type 1 replication in
      vitro. These include the tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one
      and -thione (TIBO) and the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine
      (HEPT) derivatives. Both the TIBO and HEPT derivatives specifically inhibit human
      immunodeficiency virus type 1 reverse transcriptase (RT). From a comparative
      study of the characteristics of RT inhibition by TIBO and HEPT, and from the
      competition between TIBO and HEPT for RT inhibition, we infer that both classes
      of compounds, although structurally unrelated, are targeted at the same site of
      the enzyme. Detailed functional and kinetic analyses indicate that this target
      site is functionally and possibly also spatially related to the substrate binding
      site.

PMID- 1375321
TI  - GTPase-activating protein and phosphatidylinositol 3-kinase bind to distinct
      regions of the platelet-derived growth factor receptor beta subunit.
AB  - In response to binding of platelet-derived growth factor (PDGF), the PDGF
      receptor (PDGFR) beta subunit is phosphorylated on tyrosine residues and
      associates with numerous signal transduction enzymes, including the GTPase
      activating protein of ras (GAP) and phosphatidylinositol 3-kinase (PI3K).
      Previous studies have shown that association of PI3K requires phosphorylation of
      tyrosine 751 (Y751) in the kinase insert and that this region of receptor forms
      at least a portion of the binding site for PI3K. In this study, the in vitro
      binding of GAP to the PDGFR was investigated. Like PI3K, GAP associates only with
      receptors that have been permitted to autophosphorylate, and GAP itself does not
      require tyrosine phosphate in order to stably associate with the phosphorylated
      PDGFR. To define which tyrosine residues are required for GAP binding, a panel of
      PDGFR phosphorylation site mutants was tested. Mutation of Y771 reduced the
      amount of GAP that associates to an undetectable level. In contrast, the F771
      (phenylalanine at 771) mutant bound wild-type levels of PI3K, whereas the F740
      and F751 mutants bound 3 and 23%, respectively, of the wild-type levels of PI3K
      but wild-type levels of GAP. The F740/F751 double mutant associated with wild
      type levels of GAP, but no detectable PI3K activity, while the F740/F751/F771
      triple mutant could not bind either GAP or PI3K. The in vitro and in vivo
      associations of GAP and PI3K activity to these PDGFR mutants were
      indistinguishable. The distinct tyrosine residue requirements suggest that GAP
      and PI3K bind different regions of the PDGFR. This possibility was also supported
      by the observation that the antibody to the PDGFR kinase insert Y751 region that
      blocks association of PI3K had only a minor effect on the in vitro binding of
      GAP. In addition, highly purified PI3K and GAP associated in the absence of other
      cellular proteins and neither cooperated nor competed with each other's binding
      to the PDGFR. Taken together, these studies indicate that GAP and PI3K bind
      directly to the PDGFR and have discrete binding sites that include portions of
      the kinase insert domain.

PMID- 1375322
TI  - Specific cleavage of pre-edited mRNAs in trypanosome mitochondrial extracts.
AB  - RNA editing in Trypanosoma brucei is a posttranscriptional processing event that
      results in the addition and deletion of uridine residues within several
      mitochondrial mRNAs. We have examined reactions involving pre-edited precursor
      RNAs in vitro. In this study, we report specific cleavage of pre-edited
      cytochrome b (CYb), cytochrome oxidase subunit II (COII), and cytochrome oxidase
      subunit III (COIII) mRNAs when incubated with T. brucei mitochondrial extracts.
      The pre-edited CYb RNA was cleaved near the 3'-most uridine addition sites,
      within the region where editing would be expected to commence. Pre-edited COII
      mRNA was similarly cleaved adjacent to its small editing domain, while pre-edited
      COIII RNA was cleaved at multiple sites in the region where uridine addition and
      deletion occurs in vivo. In contrast, edited versions of CYb, COII, and COIII
      RNAs were not cleaved within the editing domains. Such differential cleavage of
      the edited and pre-edited forms of these mRNAs suggests either a direct
      involvement in RNA editing or involvement in another aspect of mitochondrial gene
      expression requiring cleavage of pre-edited RNAs.

PMID- 1375323
TI  - Specific isoprenoid modification is required for function of normal, but not
      oncogenic, Ras protein.
AB  - While the Ras C-terminal CAAX sequence signals modification by a 15-carbon
      farnesyl isoprenoid, the majority of isoprenylated proteins in mammalian cells
      are modified instead by a 20-carbon geranylgeranyl moiety. To determine the
      structural and functional basis for modification of proteins by a specific
      isoprenoid group, we have generated chimeric Ras proteins containing C-terminal
      CAAX sequences (CVLL and CAIL) from geranylgeranyl-modified proteins and a
      chimeric Krev-1 protein containing the H-Ras C-terminal CAAX sequence (CVLS). Our
      results demonstrate that both oncogenic Ras transforming activity and Krev-1
      antagonism of Ras transforming activity can be promoted by either farnesyl or
      geranylgeranyl modification. Similarly, geranylgeranyl-modified normal Ras
      [Ras(WT)CVLL], when overexpressed, exhibited the same level of transforming
      activity as the authentic farnesyl-modified normal Ras protein. Therefore,
      farnesyl and geranylgeranyl moieties are functionally interchangeable for these
      biological activities. In contrast, expression of moderate levels of
      geranylgeranyl-modified normal Ras inhibited the growth of untransformed NIH 3T3
      cells. This growth inhibition was overcome by coexpression of the mutant protein
      with oncogenic Ras or Raf, but not with oncogenic Src or normal Ras. The similar
      growth-inhibiting activities of Ras(WT)CVLL and the previously described Ras(17N)
      dominant inhibitory mutant suggest that geranylgeranyl-modified normal Ras may
      exert its growth-inhibiting action by perturbing endogenous Ras function. These
      results suggest that normal Ras function may specifically require protein
      modification by a farnesyl, but not a geranylgeranyl, isoprenoid.

PMID- 1375324
TI  - The promoter of the CD19 gene is a target for the B-cell-specific transcription
      factor BSAP.
AB  - The CD19 protein is expressed on the surface of all B-lymphoid cells with the
      exception of terminally differentiated plasma cells and has been implicated as a
      signal-transducing receptor in the control of proliferation and differentiation.
      Here we demonstrate complete correlation between the expression pattern of the
      CD19 gene and the B-cell-specific transcription factor BSAP in a large panel of B
      lymphoid cell lines. The human CD19 gene has been cloned, and several BSAP
      binding sites have been mapped by in vitro protein-DNA binding studies. In
      particular, a high-affinity BSAP-binding site instead of a TATA sequence is
      located in the -30 promoter region upstream of a cluster of heterogeneous
      transcription start sites. Moreover, this site is occupied by BSAP in vivo in a
      CD19-expressing B-cell line but not in plasma or HeLa cells. This high-affinity
      site has been conserved in the promoters of both human and mouse CD19 genes and
      was furthermore shown to confer B-cell specificity to a beta-globin reporter gene
      in transient transfection experiments. In addition, BSAP was found to be the only
      abundant DNA-binding activity of B-cell nuclear extracts that interacts with the
      CD19 promoter. Together, this evidence strongly implicates BSAP in the regulation
      of the CD19 gene.

PMID- 1375326
TI  - Structural requirements for enhancement of T-cell responsiveness by the
      lymphocyte-specific tyrosine protein kinase p56lck.
AB  - To understand the mechanism(s) by which p56lck participates in T-cell receptor
      (TCR) signalling, we have examined the effects of mutations in known regulatory
      domains of p56lck on the ability of F505 p56lck to enhance the responsiveness of
      an antigen-specific murine T-cell hybridoma. A mutation of the amino-terminal
      site of myristylation (glycine 2), which prevents stable association of p56lck
      with the plasma membrane, completely abolished the ability of F505 p56lck to
      enhance TCR-induced tyrosine protein phosphorylation. Alteration of the major
      site of in vitro autophosphorylation, tyrosine 394, to phenylalanine diminished
      the enhancement of TCR-induced tyrosine protein phosphorylation by F505 p56lck.
      Such a finding is consistent with the previous demonstration that this site is
      required for full activation of p56lck by mutation of tyrosine 505. Strikingly,
      deletion of the noncatalytic Src homology domain 2, but not of the Src homology
      domain 3, markedly reduced the improvement of TCR-induced tyrosine protein
      phosphorylation by F505 Lck. Additional studies revealed that all the mutations
      tested, including deletion of the Src homology 3 region, abrogated the
      enhancement of antigen-triggered interleukin-2 production by F505 p56lck, thus
      implying more stringent requirements for augmentation of antigen responsiveness
      by F505 Lck. Finally, it was also observed that expression of F505 p56lck greatly
      increased TCR-induced tyrosine phosphorylation of phospholipase C-gamma 1,
      raising the possibility that phospholipase C-gamma 1 may be a substrate for
      p56lck in T lymphocytes. Our results indicate that p56lck regulates T-cell
      antigen receptor signalling through a complex process requiring multiple distinct
      structural domains of the protein.

PMID- 1375325
TI  - Multiple cDNAs encoding the esk kinase predict transmembrane and intracellular
      enzyme isoforms.
AB  - A novel protein kinase, the Esk kinase, has been isolated from an embryonal
      carcinoma (EC) cell line by using an expression cloning strategy. Sequence
      analysis of two independent cDNA clones (2.97 and 2.85 kb) suggested the presence
      of two Esk isoforms in EC cells. The esk-1 cDNA sequence predicted an 857-amino
      acid protein kinase with a putative membrane-spanning domain, while the esk-2
      cDNA predicted an 831-amino-acid kinase which lacked this domain. In adult mouse
      cells, esk mRNA levels were highest in tissues possessing a high proliferation
      rate or a sizeable stem cell compartment, suggesting that the Esk kinase may play
      some role in the control of cell proliferation or differentiation. As anticipated
      from the screening procedure, bacterial expression of the Esk kinase reacted with
      antiphosphotyrosine antibodies on immunoblots. Furthermore, in in vitro kinase
      assays, the Esk kinase was shown to phosphorylate both itself and the exogenous
      substrate myelin basic protein on serine, threonine, and tyrosine residues,
      confirming that the Esk kinase is a novel member of the serine/threonine/tyrosine
      family of protein kinases.

PMID- 1375327
TI  - Psoralen damage-induced plasmid recombination in Saccharomyces cerevisiae:
      dependence on RAD1 and RAD52.
AB  - Photoreaction with psoralen, a DNA-crosslinking reagent, induces mitotic
      recombination in the yeast Saccharomyces cerevisiae. Psoralen damage-induced
      recombination was studied with non-replicating plasmids, which transform yeast
      cells by undergoing recombination events with chromosomal DNA. When plasmid DNA
      was photoreacted with psoralen in vitro and transformed into yeast cells,
      transformation was stimulated by psoralen modification in a dose-dependent
      manner. The stimulation by psoralen damage requires RAD52 gene function and is
      partially dependent on RAD1. Analysis of transformants indicates that plasmid
      integration occurs at the homologous chromosomal loci. Multiple tandem
      integrations are common in repair-proficient cells, with more than 20 copies of
      integrated plasmid seen in some transformants. Multiple integration depends on
      RAD1 function; only 9% of rad1 transformants, compared to 80% of RAD
      transformants, contained multiple plasmid copies, while 52% of the rad1
      transformants were produced by gene conversion.

PMID- 1375329
TI  - Quantitative detection of DNA damage in cells after exposure to ionizing
      radiation by means of an improved immunochemical assay.
AB  - A simple, sensitive and fast immunochemical method has been developed to quantify
      the amount of DNA damage in cells of human blood after in vitro exposure to
      ionizing radiation. The technique is based on the enhancement of the radiation
      induced single-strandedness, which occurs in DNA regions flanking strand breaks,
      by a controlled further unwinding of the DNA in an alkaline solution.
      Subsequently, the DNA is attached to the wall of polystryene cups by passive
      adsorption. DNA damage is then quantified by determining the extent of single
      strandedness with a monoclonal antibody, D1B, directed against single-stranded
      DNA. D1B binding is assayed with a 'second' antibody, labelled with either an
      enzyme or europium. The latter gives slightly more reproducible results. No
      radioactive labelling of DNA is required and the assay takes only 3.5 h after the
      collection of blood. Damage can be detected after doses as low as 0.5 Gy. The
      potential broader application of the method is discussed.

PMID- 1375328
TI  - Nuclease modification in Chinese hamster cells hypersensitive to DNA cross
      linking agents--a model for Fanconi anemia.
AB  - Fanconi anemia is a human inherited disease that is characterized by cellular
      hypersensitivity to DNA cross-linking agents. A number of potential experimental
      models for that disorder have been developed by selecting mutants that are
      hypersensitive to bifunctional mutagens. The six mutants of that class in
      Drosophila, all of which map to the mus308 locus, express an alteration in a
      mitochondrial nuclease. A recent extension of that observation to cell lines from
      complementation group A of Fanconi anemia has established a new cellular
      phenotype for that disorder. In the current study an analogous enzyme has been
      analyzed in eight recently isolated Chinese hamster cell lines that are
      hypersensitive to cross-linking agents. Among these lines. V-H4 and V-B7 are
      shown to exhibit an enzyme modification analogous to that observed in the mutant
      Drosophila and human cells. These results validate the nuclease assay as an
      indicator of the Fanconi defect and further establish the V-H4 cell line as a
      valuable cellular model for analysis of the Fanconi A defect.

PMID- 1375330
TI  - HeLa cell single-stranded DNA-binding protein increases the accuracy of DNA
      synthesis by DNA polymerase alpha in vitro.
AB  - To determine whether cellular replication factors can influence the fidelity of
      DNA replication, the effect of HeLa cell single-stranded DNA-binding protein
      (SSB) on the accuracy of DNA replication by HeLa cell DNA polymerase alpha has
      been examined. An in vitro gap-filling assay, in which the single-stranded gap
      contains the supF target gene, was used to measure mutagenesis. Addition of SSB
      to the in vitro DNA synthesis reaction increased the accuracy of DNA polymerase
      alpha by 2- to 8-fold. Analysis of the products of DNA synthesis indicated that
      SSB reduces pausing by the polymerase at specific sites in the single-stranded
      supF template. Sequence analysis of the types of errors resulting from synthesis
      in the absence or presence of SSB reveals that, while the errors are primarily
      base substitutions under both conditions, SSB reduces the number of errors found
      at 3 hotspots in the supF gene. Thus, a cellular replication factor (SSB) can
      influence the fidelity of a mammalian DNA polymerase in vitro, suggesting that
      the high accuracy of cellular DNA replication may be determined in part by the
      interaction between replication factors, DNA polymerase and the DNA template in
      the replication complex.

PMID- 1375331
TI  - Determinants of cisplatin sensitivity in non-malignant non-drug-selected human T
      cell lines.
AB  - We have studied molecular mechanisms of cisplatin sensitivity and resistance in 3
      non-malignant, non-drug-selected human T lymphocyte cell lines. HuT 78, H9, and
      MOLT-4 cells were assessed for sensitivity to cisplatin, DNA damage levels
      following defined drug exposures, drug accumulation, and DNA repair efficiency as
      measured by adduct removal from cellular DNA and by host-cell reactivation of
      cisplatin-modified plasmid DNA. Based on 3-day continuous drug exposures, the
      IC50 values for the cell lines were: HuT 78, 0.83 microM; H9, 0.45 microM; and
      MOLT-4, 0.33 microM. These cells retained this order with respect to DNA repair
      capability, whether measured by platinum-DNA adduct removal from cellular DNA or
      by host-cell reactivation assays. DNA repair values measured by these two assays
      were directly related to one another with a linear correlation coefficient of
      0.993. At sublethal cisplatin doses the more resistant cells showed the highest
      levels of drug uptake. When drug uptake levels were 'corrected' for drug-induced
      cell kill, there were equal levels of DNA repair efficiency for a given level of
      drug uptake. Absolute levels of cisplatin-DNA adduct repair increased with
      increasing drug dose. However, at supralethal doses of drug, efficient DNA repair
      could be overcome in all 3 cell lines with percentage-adduct-removal dropping
      from a 60-80% range to a less than 30% range. We conclude that in non-malignant
      non-drug-selected human T cells, DNA repair appears to be the primary determinant
      of cisplatin sensitivity/resistance and that enhanced DNA repair may be a
      biologic compensatory mechanism for cells that cannot prevent cellular uptake of
      DNA-damaging agents.

PMID- 1375332
TI  - Transcription-dependent and independent DNA excision repair pathways in human
      cells.
AB  - alpha-Amanitin, an inhibitor of RNA polymerase II, has little effect on either UV
      induced incision or repair synthesis in cultured normal human fibroblasts but
      almost completely inhibits both processes in xeroderma pigmentosum group C
      fibroblasts. Cycloheximide, at a concentration which inhibits protein synthesis
      by 75-80%, has no effect on incision or repair synthesis in either cell type,
      which argues that the effects of alpha-amanitin on repair occur at the level of
      transcription. Cot analysis demonstrates that UV-induced repair synthesis occurs
      at similar levels in highly repetitive, middle repetitive and single copy
      sequence in both normal and xeroderma group C cells. We conclude that normal
      cells must have at least two excision repair pathways for repair of UV-induced
      damage, one dependent on transcription and the other independent.

PMID- 1375333
TI  - Differences in DNA damage induced by mutagenic and nonmutagenic 4-aminoazobenzene
      derivatives in Escherichia coli.
AB  - DNA lesions produced in Escherichia coli AB2500 (uvrA) exposed to the carcinogen
      N-hydroxy-3-methoxy-4-aminoazobenzene (N-OH-3-MeO-AAB) or the noncarcinogen N
      hydroxy-2-methoxy-4-aminoazobenzene (N-OH-2-MeO-AAB) were investigated by
      alkaline sucrose gradient sedimentation and 32P-postlabeling analysis. Alkali
      labile sites appeared to be formed equally in cells treated with both
      aminoazobenzene derivatives. 32P-Postlabeling analysis revealed that the 3-MeO
      AAB-DNA adduct level was 25-fold higher than that for 2-MeO-AAB-DNA adducts. In
      addition to major adducts, 4 minor spots were detected in N-OH-3-MeO-AAB-treated
      cells, while only one major adduct was found in N-OH-2-MeO-AAB-treated cells. The
      mutagenicities and cytotoxicities were also determined with E. coli with
      different repair capacities; we found that repair of 3-MeO-AAB damages is
      strongly dependent on the UVR repair system. Moreover, N-OH-3-MeO-AAB, but not N
      OH-2-MeO-AAB, could induce recA and umuC gene expression, which was higher in
      uvrA strains than in the wild type.

PMID- 1375334
TI  - Investigation of the mutagenic activity in Salmonella typhimurium of the
      furochromone khellin, proposed as a therapeutic agent for skin diseases.
AB  - The photomutagenicity of the furochromone khellin was tested in Ames Salmonella
      strains using 8-methoxypsoralen (8-MOP) and 4,5', 8-trimethylpsoralen (TMP) as
      positive controls. When khellin was assayed with strain TA1537, mutation
      induction was not detectable; in the same strain, an equitoxic dose (52-56% level
      of survival) of TMP (used at a concentration 12-fold lower than khellin and with
      a UVA dose 83-fold lower than that used with khellin) yielded an increase in
      revertants/plate 3-fold above the spontaneous background. In strain TA102,
      khellin plus UVA treatment yielded a 2-fold increase in revertants/plate above
      the spontaneous background (79% survival). 8-MOP, however, used at a
      concentration 8-fold lower than khellin with a UVA dose 13-fold lower than
      khellin, yielded an increase in revertants/plate about 14-fold above background
      (66% survival) in the same strain. These data show that khellin has a weak
      photomutagenic potential and, along with the previously reported low
      photogenotoxic potential in eukaryotic cell systems, support the notion that
      khellin may be safer than bifunctional psoralens for clinical use.

PMID- 1375335
TI  - Cytotoxicity and genotoxicity testing of sodium fluoride on Chinese hamster V79
      cells and human EUE cells.
AB  - The cytotoxic effects of sodium fluoride (NaF) on hamster V79 cells and human EUE
      cells were studied by measuring the cloning efficiency and DNA, RNA and protein
      synthesis in cells cultured in the presence of NaF. Potential mutagenicity of NaF
      was followed on the basis of induced 6-thioguanine-resistant mutants in treated
      Chinese hamster V79 cells. The results showed that the addition of 10-150
      micrograms of NaF per ml of culture medium induced 10-75% cytotoxic effect on
      hamster V79 cells but had no toxic effect on human EUE cells. NaF was cytotoxic
      to human EUE cells at considerably higher concentrations (200-600 micrograms/ml).
      Growth of both cell types with 100 and 200 micrograms of NaF per ml caused
      inhibition of 14C-thymidine, 14C-uridine and 14C-L-leucine incorporation. This
      means that NaF inhibits macromolecular synthesis whereby damaging effects were
      less drastic in human EUE cells. The results of detailed mutagenicity testing on
      hamster V79 cells showed that NaF did not show any mutagenic effect after long
      term (24-h) incubation of hamster cells in the presence of 10-400 micrograms of
      NaF per ml of culture medium.

PMID- 1375336
TI  - Sister-chromatid exchanges in operating room personnel.
AB  - Sister-chromatid exchange (SCE) analysis was carried out in 67 operating room
      personnel (anaesthetists M.D.; anaesthesia nurses and anaesthesia unit
      technicians) exposed to waste anaesthetic gases such as halothane, nitrous oxide
      and isoflurane and in 50 healthy unexposed controls. The SCE frequencies were
      increased significantly in operating room personnel as compared to controls. A
      significant increase in SCEs was found in non-smoking operating room personnel as
      compared to non-smoking controls. This study supports the existence of an
      association between occupational exposure to mutagens and an increase in SCEs in
      lymphocytes.

PMID- 1375337
TI  - Protective effect of two sunscreens against lethal and genotoxic effects of UVB
      in V79 Chinese hamster cells and Saccharomyces cerevisiae strains XV185-14C and
      D5.
AB  - Effects of p-aminobenzoic acid (PABA) and of 4-[(2-oxo-3-bornylidene)methyl]
      phenyl trimethylammonium methylsulfate (OMM), two components used in sunscreen
      formulations, on the mutagenicity of UVB irradiation are compared in three
      genetic assay systems. A haploid strain of Saccharomyces cerevisiae XV185-14C was
      used to measure reverse mutations at three loci. The diploid strain D5 of
      Saccharomyces cerevisiae was used to screen for reciprocal mitotic recombination.
      The induction of forward mutations was measured in Chinese hamster V79 cells. Our
      results indicate that UVB irradiation induced HGPRT- mutants in V79 cells,
      reverse mutations in Saccharomyces cerevisiae strain XV185-14C, and mitotic
      crossing over and other genetic alterations in Saccharomyces cerevisiae strain
      D5. V79 Chinese hamster lung cells were the most sensitive to UVB irradiation,
      followed by Saccharomyces cerevisiae haploid strain XV185-14C and the diploid
      strain D5. PABA and OMM were both capable of protecting all three types of cells
      from UVB irradiation regarding both lethality and induction of various types of
      genetic alterations. At higher concentrations (above 10(-5) M), OMM was more
      effective in its photoprotective effect toward UVB irradiation than PABA.

PMID- 1375338
TI  - Biomonitoring of genotoxic exposure among stainless steel welders.
AB  - A biosurvey in the Danish metal industry measured the genotoxic exposure from
      stainless steel welding. The study comprised measurements of chromosomal
      aberrations (CA), sister-chromatid exchanges (SCE), unscheduled DNA synthesis
      (UDS) in peripheral lymphocytes and serum immunoglobulin G. Environmental
      monitoring of welding fumes and selected metal oxides, biomonitoring of chromium
      and nickel in serum and urine and mutagenic activity in urine, and evaluation of
      semen quality were also done. Manual metal arc (MMA) welding and tungsten inert
      gas (TIG) welding were the dominant welding processes. A higher frequency of
      chromosomal aberrations, classified as translocations, double minutes, exchanges
      and rings, was observed in stainless steel welders than in non-welders. SCE was
      lower in welders working with both MMA and TIG welding than in reference persons.
      N-Acetoxy-N-acetylaminofluorene (NA-AAF)-induced UDS was lower in 23 never
      smoking welders than in 19 unexposed never-smokers. Smoking was a confounding
      factor resulting in significantly higher CA, SCE, NA-AAF binding to DNA and
      mutagenic activity in urine. Age was also a confounder: CA, SCE, NA-AAF binding
      to DNA and UDS increased significantly with age. No significant correlation
      between SCE and CA or between CA and UDS was found. UDS decreased significantly
      with increasing lymphocyte count and a higher lymphocyte count was seen in MMA
      welders than in reference persons and in smokers than in non-smokers. Differences
      in the composition among lymphocytes in exposed persons compared with non-exposed
      are suggested. MMA welding gave the highest exposure to chromium, an increased
      number of chromosomal aberrations and a decrease in SCE when compared with TIG
      welding. Consequently improvements in the occupational practice of stainless
      steel welding with MMA is recommended.

PMID- 1375339
TI  - Frequencies of chromosomal aberrations in pesticide sprayers working in plastic
      green houses.
AB  - The frequency of chromosome aberrations was studied in peripheral blood
      lymphocytes of 29 workers occupationally exposed to a mixture of pesticides and
      in 14 age- and sex-matched healthy controls. There was a significant increase in
      chromosome aberrations in sprayers when compared to unexposed persons (2.39%
      compared to 0.54%). No positive correlation between the frequency of chromosome
      aberrations and the duration of exposure was observed. No significant difference
      between smokers and non-smokers was found.

PMID- 1375340
TI  - Comparison of mutation frequencies obtained using transgenes and specific-locus
      mutation systems in male mouse germ cells.

PMID- 1375341
TI  - Sister-chromatid exchanges induced by vinyl esters and respective carboxylic
      acids in cultured human lymphocytes.
AB  - Vinyl acetate--an efficient inducer of sister-chromatid exchanges (SCEs)--is
      known to be hydrolyzed in mammalian cells into acetic acid and acetaldehyde, the
      latter being the likely metabolite responsible for the SCE induction. As similar
      hydrolysis to acetaldehyde and to a carboxylic acid is also expected for other
      vinyl esters, five such compounds--vinyl formate, vinyl chloroformate, vinyl
      propionate, vinyl crotonate and vinyl-2-ethylhexanoate--and five carboxylic acids
      -formic acid, acetic acid, propionic acid, crotonic acid and 2-ethylhexanoic acid
      -were tested for their ability to induce SCEs in cultured (72 h) human
      lymphocytes with a 48-h treatment, starting at 24 h after culture initiation.
      Vinyl formate, vinyl propionate and vinyl crotonate induced a clear dose
      dependent increase in the number of SCEs/cell at concentrations of 0.125-0.5 mM
      and vinyl chloroformate at 0.063-1 mM, i.e., at roughly the same concentration
      range as vinyl acetate and acetaldehyde. Vinyl-2-ethylhexanoate required slightly
      higher concentrations (0.25-4 mM) for SCE induction. All of the carboxylic acids
      tested also elevated SCEs, but only slightly. Formic acid and crotonic acid
      produced some SCE increase at a concentration of 10 mM, acetic acid at 5 and 10
      mM and propionic acid at 2.5 mM. 2-Ethylhexanoic acid induced SCEs at a lower
      concentration range (0.63-2.5 mM) than the other acids. The positive
      concentrations of the first three carboxylic acids lowered the pH of the culture
      medium immediately after the treatment by 0.5-1.0 pH unit (lowest observed pH
      6.53). The pH differences from the control cultures became smaller in
      measurements done 24 h and 48 h after the beginning of treatment. Propionic acid
      and 2-ethylhexanoic acid affected medium pH only slightly (maximum drop 0.2 pH
      units) at the concentrations that induced SCEs. The results lend support to the
      idea that the efficient SCE induction observed with the vinyl esters results from
      the formation of acetaldehyde, with carboxylic acids--with the possible exception
      of 2-ethylhexanoic acid--playing no significant role. The slight SCE induction
      obtained with the carboxylic acids cannot be explained by lowered pH alone.

PMID- 1375342
TI  - Enhanced mutagenicity of anisidine isomers in bacterial strains containing
      elevated N-acetyltransferase activity.
AB  - In previous studies on the mutagenicity of anisidine isomers, the ortho isomer
      was considered to be mutagenic towards standard Ames tester strains, while the
      para isomer gave equivocal results. In the present study we show that both para-
      and ortho-anisidine isomers are mutagenic in a Salmonella typhimurium tester
      strain containing elevated levels of N-acetyltransferase (YG1029). p-Anisidine
      gave a positive mutagenic response using either hamster S9 or ram seminal vesicle
      microsomes (RSVM) as an activating system, while o-anisidine gave a positive
      response only with the hamster S9 fraction. The mutagenic response from p
      anisidine was greater than with o-anisidine in each case. In tests with p
      anisidine and RSVM, the addition of arachidonic acid was not necessary to observe
      a mutagenic response. Catalase produced a dose-dependent decrease in the
      mutagenic response with p-anisidine and RSVM; this indicates that endogenous
      hydrogen peroxide from the bacteria acts as a substrate for the peroxidase
      activity of RSVM prostaglandin H synthase. These results demonstrate that both
      anisidine isomers are mutagenic and that N-acetyltransferase enzymes play an
      important role in their metabolism to mutagenic species.

PMID- 1375343
TI  - Analysis of mutagenic activity and ability to induce replication of polyoma DNA
      sequences by different model metabolites of the carcinogenic tobacco-specific
      nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
AB  - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) requires metabolic activation to express its carcinogenic activity. This
      activation leads to the formation of methylating and pyridyloxobutylating agents.
      To determine the possible biological effects mediated by each of these metabolic
      pathways we have studied the activities of model compounds that are metabolized
      to either a methylating or pyridyloxobutylating species. Each model compound was
      evaluated for its mutagenic activity in both prokaryotic and eukaryotic cell
      systems. The model compounds were also tested for their ability to induce
      asynchronous replication of viral DNA sequences. We demonstrate here that both
      the methylating model compound acetoxymethylmethylnitrosamine (AMMN) and the
      pyridyloxobutylating model compound 4-(acetoxymethyl)-1-(3-pyridyl)-1-butanone
      (NNKOAc) were mutagenic in strains TA98, TA100, and TA1535 but not TA102. While
      NNKOAc appeared to be 10 times more potent than AMMN in Salmonella, AMMN was
      found to be a more potent mutagen in mammalian G12 cells. Both chemicals could
      induce asynchronous replication of polyoma DNA sequences in rat fibroblast cells
      carrying an integrated copy of the polyoma virus with AMMN appearing to be more
      active. Measurement of DNA adduct levels suggest that the damage produced by
      NNKOAc was at least as active as that produced by AMMN when viewed on a per
      adduct basis. The possible implications of the biological activities exhibited by
      methylating and pyridyloxobutylating model compounds to NNK induced
      carcinogenesis are discussed.

PMID- 1375345
TI  - Muddled carbon tax.

PMID- 1375344
TI  - Brief report: treatment of chronic inflammatory bowel disease in glycogen storage
      disease type Ib with colony-stimulating factors.

PMID- 1375346
TI  - Evolutionary chemistry. Life in a test tube.

PMID- 1375348
TI  - [The endoscopic diagnosis of reflux esophagitis: the value of color endoscopy].

PMID- 1375347
TI  - Irreversible association of peptides with class II MHC molecules in living cells.
AB  - Functional, morphological and biochemical evidence indicates that class II major
      histocompatibility complex (MHC) molecules associate with processed peptides
      during biosynthesis. Peptide/MHC complexes in living cells have been reported to
      be less stable than similar complexes generated in vitro, which has led to the
      suggestion that there may be a peptide exchange mechanism operating in vivo.
      Although this could increase the capacity for binding incoming antigens, it would
      reduce the efficacy of processed antigenic peptides by exchanging these for self
      peptides. Here we measure the half-life of peptide/class II complexes in human
      antigen-presenting cells and find that it is very similar to the half-life of
      class II molecules themselves, indicating that peptides are bound irreversibly
      under physiological conditions. Thus class II MHC retains long-term 'memory' of
      past encounters with antigen to maximize the opportunity for T cell/antigen
      presenting cell interaction.

PMID- 1375349
TI  - [Laser therapy in the palliative treatment of esophageal neoplasms].

PMID- 1375350
TI  - Caudal ventrolateral medullary projections to the nucleus of the solitary tract
      in the cat.
AB  - The projections of neurons, in and around the A1 noradrenergic cell group of the
      caudal ventrolateral medulla (VLM), to nucleus of the solitary tract (NTS) were
      studied in the cat using the anterograde transport of Phaseolus vulgaris
      leucoagglutinin (PHA-L). PHA-L was micro-iontophoresed into the region of the A1
      noradrenergic cell group and after a 7-17 day survival period animals were
      sacrificed and brainstem sections were processed for PHA-L or tyrosine
      hydroxylase (TH) immunoreactivity. PHA-L injections within the region of the A1
      cell group resulted in labelled fibers with their presumptive terminal boutons
      primarily in the ipsilateral commissural and medial subnuclei of NTS. A light
      projection to the ipsilateral parvocellular lateral and ventrolateral subnuclei
      of the NTS complex was also observed. These data demonstrate that neurons in the
      region of the A1 noradrenergic cell group project to regions of NTS that receive
      cardiovascular afferent inputs and suggest that VLM may influence the activity of
      neurons in NTS involved in the reflex regulation of the circulation.

PMID- 1375351
TI  - Serotonin-, substance P- and tyrosine hydroxylase-like immunoreactive neurons
      projecting from the midbrain periaqueductal gray to the nucleus tractus solitarii
      in the rat.
AB  - Serotonin-, substance P- and tyrosine hydroxylase-like immunoreactive neurons in
      the midbrain periaqueductal gray (PAG) were observed to send their axons to the
      nucleus tractus solitarii in the rat by the retrograde horseradish peroxidase
      tracing method combined with the immunocytochemical technique. These neurons were
      most frequently observed in the ventrolateral subnucleus and ventral portion of
      the medial subnucleus of the PAG at the entire rostrocaudal levels.

PMID- 1375352
TI  - The cGMP-gated channel of rod outer segments is not localized in bipolar cells of
      the mammalian retina.
AB  - It has recently been suggested (Nature, 346 (1990) 269-271) that ON-bipolar cells
      express the same biochemical cascade and guanosine 3',5'-cyclic monophosphate
      (cGMP)-gated cation channel as rod outer segments. An antibody directed against
      the cGMP-gated channel of bovine rod outer segments was applied to cryostat
      sections of rat and cat retinae. No immunocytochemical labelling was found in
      bipolar cells. Therefore, if those cells express a cGMP-gated channel, it must be
      immunologically different to the 63 kDa protein constituting the cGMP-gated
      channel of the outer segment.

PMID- 1375353
TI  - High and low affinity membrane binding sites for fibroblast growth factors in the
      developing chick brain.
AB  - Acidic and basic fibroblast growth factors (aFGF and bFGF), two mitogenic,
      neurotrophic and angiogenic molecules, are present in the embryonic chick brain
      but their function remains unclear. In order to approach the biological activity
      of FGFs during brain development, we have looked for their receptors and studied
      their regulation through chick brain development. Competitive binding studies
      realized on brain membranes indicated the presence of two classes of FGF binding
      sites: high affinity binding sites (dissociation constant, Kd = 100 pM) and low
      affinity binding sites (Kd = 20 nM). Cross-competition experiments show that
      these two classes of binding sites both interact with aFGF and bFGF. The number
      of sites in these two classes of binding sites changes during embryogenesis. On
      the one hand, the membrane capacity of high affinity sites decreases from E7 (1
      +/- 0.2 pmol/mg of protein) to E15 (0.5 +/- 0.2 pmol/mg of protein); on the other
      hand, the membrane capacity of low affinity sites increases from E15 (25 +/- 4
      pmol/mg of protein) to P1 (75 +/- 20 pmol/mg of protein). Cross-linking
      experiments revealed the presence of two putative receptor forms of molecular
      masses of about 130 and 95 kDa. These results suggest that the biological
      activity of aFGF and bFGF during brain embryogenesis could be regulated by the
      expression of high and low affinity binding sites for these growth factors.

PMID- 1375355
TI  - Automatic implantable cardioverter therapy: lessons from the 1980s, expectations
      for the 1990s.

PMID- 1375354
TI  - Apolipoprotein B immunoreactivity in senile plaque and vascular amyloids and
      neurofibrillary tangles in the brains of patients with Alzheimer's disease.
AB  - Based upon our previous finding of the association of apolipoprotein E (apoE)
      immunoreactivity with cerebral amyloids and neurofibrillary tangles (NFTs), we
      examined immunohistochemically whether this is also the case for apolipoprotein B
      (apoB). Polyclonal antibody to apoB immunosustained senile plaque amyloid,
      vascular amyloid, subpial amyloid deposits and intracellular NFTs in formalin
      fixed, paraffin-embedded brain sections from patients with Alzheimer disease.
      Hydrated autoclave pretreatment of the sections enhanced the staining of plaque
      amyloid. The results may suggest a role of apoB in amyloid and NFT formation.

PMID- 1375356
TI  - Automatic implantable cardioverter defibrillator therapy: lessons from the 1980s,
      expectations for the 1990s. Proceedings of an international symposium. Brussels,
      October 17-19, 1991.

PMID- 1375357
TI  - Historical milestones of implanted defibrillation.

PMID- 1375358
TI  - The automatic implantable cardioverter defibrillator: review of clinical results,
      1980-1990.

PMID- 1375360
TI  - The role of the ICD in patients with dilated and hypertrophic cardiomyopathy.

PMID- 1375359
TI  - Implantable cardioverter defibrillator therapy: indications and decision making
      in patients with coronary artery disease.

PMID- 1375361
TI  - Idiopathic ventricular tachycardia and fibrillation: incidence, prognosis, and
      therapy.

PMID- 1375362
TI  - Implantable cardioverter defibrillators: surgical considerations.

PMID- 1375363
TI  - Assessment of the defibrillation threshold and appropriate sensing during
      cardioverter defibrillator implantation.

PMID- 1375365
TI  - Effects of antiarrhythmic drugs on defibrillation threshold in patients with the
      implantable cardioverter defibrillator.

PMID- 1375364
TI  - The implantable cardioverter defibrillator and concomitant coronary artery bypass
      grafting: special considerations.

PMID- 1375366
TI  - Factors associated with implantation-related complications.

PMID- 1375367
TI  - Infections involving implanted cardioverter defibrillator devices.
AB  - Infection is one of the most serious complications in patients with an implanted
      cardioverter defibrillator. The diagnosis is facilitated by computed tomographic
      and radionuclide imaging. Infection may be caused by intraoperative contamination
      or hematogenous seeding. In view of the serious consequences, the emphasis should
      be on prevention of these events. Perioperative antibiotic prophylaxis is common
      practice but the utility of prophylactic antibiotic remote from surgery is
      questionable. Strict adherence to asepsis and a meticulous surgical technique are
      essential. Identification of risk factors in the individual patient allows a
      patient-tailored treatment policy that may add to infection prevention. If
      implant infection does occur, complete removal of the system is most successful.

PMID- 1375368
TI  - The automatic implantable cardioverter defibrillator: limitations of the newest
      devices.

PMID- 1375369
TI  - Results and realistic expectations with transvenous lead systems.

PMID- 1375370
TI  - Antiarrhythmic drug therapy as an adjunct or alternative to an implantable
      cardioverter defibrillator.

PMID- 1375371
TI  - Role of ventricular tachycardia surgery and catheter ablation as complements or
      alternatives to the implantable cardioverter defibrillator in the 1990s.
AB  - Although the implantable cardioverter defibrillator is used increasingly, other
      nonpharmacological approaches have their indications and merits. Furthermore, as
      the natural history of ventricular tachyarrhythmias or their underlying
      structural cardiac abnormality, i.e., coronary artery disease, dilated
      cardiomyopathy, arrhythmogenic right ventricular disease, etc. change, the mode
      of therapy may be modified accordingly. Because of the disappointing results of
      the CAST study in previously asymptomatic patients after myocardial infarction
      and the evidence that failure of one or two antiarrhythmic drugs tested by
      programmed ventricular stimulation in patients with documented sustained
      ventricular tachycardia or fibrillation predicts further drug failure, there will
      be a significant increase in the use of implantable cardioverters defibrillators
      in the 1990s. However, care should be taken to avoid inappropriate use of these
      devices.

PMID- 1375372
TI  - Cost-effectiveness considerations: the Dutch prospective study of the automatic
      implantable cardioverter defibrillator as first-choice therapy.

PMID- 1375373
TI  - Prospective antiarrhythmic studies assessing prophylactic pharmacological and
      device therapy in high risk coronary patients.

PMID- 1375375
TI  - The automatic implantable cardioverter defibrillator (AICD) as a bridge to heart
      transplantation.

PMID- 1375374
TI  - Prospective studies assessing prophylactic therapy in high risk patients: the
      German Dilated CardioMyopathy Study (GDCMS)--study design.

PMID- 1375376
TI  - Principles of radiation therapy in the treatment of bone metastases.
AB  - The radiation oncologist is an important member of the multidisciplinary team
      involved in the management of patients with metastatic bone disease. Radiation
      therapy provides local tumor control of the metastatic deposit and effective pain
      relief in the majority of patients. If there is a risk of fracture, prophylactic
      fixation is done before radiation therapy.

PMID- 1375377
TI  - Postnatal placental confirmation of trisomy 2 and trisomy 16 detected at
      chorionic villus sampling: a possible association with intrauterine growth
      retardation and elevated maternal serum alpha-fetoprotein.
AB  - Detection of trisomy 2 and trisomy 16 mosaicism through chorionic villus sampling
      (CVS) is not an infrequent finding. We describe here two cases, one of non-mosaic
      trisomy 2 and the other of high level mosaicism for trisomy 16. Amniocentesis in
      both cases demonstrated non-mosaic 46,XY karyotypes. Each pregnancy continued to
      delivery of liveborn, normal-appearing boys; both pregnancies were complicated by
      severe intrauterine growth retardation (IUGR). Postnatal studies of placental
      biopsies in both cases confirmed the original CVS findings, whereas cord blood
      karyotypes were normal in both boys. Both children have demonstrated adequate
      catch-up growth.

PMID- 1375379
TI  - CA-125 as a maternal serum marker for Down's syndrome in the first and second
      trimesters.
AB  - CA-125, alpha-fetoprotein (AFP), and human chorionic gonadotropin (HCG) were
      determined in maternal serum in the first trimester from 14 women with a Down's
      syndrome fetus and 61 women with a healthy fetus. In the second trimester, 15 and
      60 serum samples were determined from women with a Down's syndrome and a healthy
      fetus respectively. In both trimesters, maternal serum CA-125 was found to be
      elevated in Down's syndrome pregnancies compared with controls. Using
      discrimination functions, our preliminary results indicate that CA-125 is a
      better marker than AFP and HCG respectively for a Down's syndrome fetus in the
      first trimester and improves the detection rate in the second trimester.

PMID- 1375378
TI  - The psychological effects of false-positive results in prenatal screening for
      fetal abnormality: a prospective study.
AB  - The purpose of the study was to describe the impact of false-positive results
      from initial maternal serum alpha-fetoprotein (MS-AFP) screening. The analyses
      compared two groups of women, those receiving a negative result (n = 346) and
      those receiving an initial positive result (n = 26), over four time points--prior
      to testing, immediately after testing, later in pregnancy, and in the post-partum
      period. Receiving an abnormal result was associated with high levels of anxiety
      which were reflected in increased worry about the baby's health and a more
      negative attitude towards the pregnancy and the baby. Women who had an initial
      abnormal result were offered a variety of further tests. Those women who went on
      to have amniocentesis were less worried about their baby's health in the third
      trimester and also less anxious post-partum than those who did not have
      amniocentesis. In view of the increasing number of screening tests available, it
      is necessary to establish whether and how these levels of distress can best be
      reduced.

PMID- 1375380
TI  - Trypanosoma cruzi: enhanced alpha-macroglobulin levels correlate with the
      resistance of BALB/cj mice to acute infection.
AB  - Trypanosoma cruzi proteinases are very likely involved in host-cell invasion.
      Physiological plasma-proteinase inhibitors from the macroglobulin (MG) family,
      among them alpha-2-macroglobulin (A2M), are found in tissues and in the plasma of
      mammals. By complexing to all classes of proteinases, MGs inhibit their action on
      high-molecular-weight substrates. In vitro studies have shown that A2M impairs T.
      cruzi proteases and, consequently, the parasite's ability to invade host cells
      and enhances the phagocytic and microbicidal actions of resident macrophages
      against T. cruzi. To test the hypothesis of a putative "protective" effect for
      MG, we quantified it in BALB/cj mice during the course of an experimental T.
      cruzi infection, comparing a posteriori the levels in mice that died with those
      in animals that survived, which were considered as being susceptible and
      resistant to the infection, respectively. The results showed that surviving mice
      showed an increase in plasma concentrations of MG during the first few weeks
      after the infection, whereas the levels in mice that died during the acute phase
      did not differ significantly from those in non-infected mice. These findings and
      the previous in vitro data indicate a role for physiological proteinase
      inhibitors, particularly alpha-macroglobulins, in resistance to T. cruzi
      infection, whereby a balance between parasite proteases and host protease
      inhibitors may be crucial. MG may thus participate in the complex network of
      reactions involved in the early acute phase of the disease and contribute by
      conferring to the host an ability to survive the infection.

PMID- 1375381
TI  - Proteoglycans in micromass cultures of embryonic mouse limb mesenchymal cells:
      preliminary studies for the "cells" spaceflight experiment.

PMID- 1375383
TI  - Dose-related involvement of CCK in bombesin-induced pancreatic growth.
AB  - We examined the role of CCK in bombesin-induced pancreatic growth in rats using
      the CCK receptor antagonist L-364,718. Rats (155 +/- 1 g, 8-10 per group)
      received subcutaneous injections every 8 h for 5 days with bombesin (0.6, 1.7 and
      5 nmol/kg) or bombesin in combination with L-364,718 (1 mg/kg). After 5 days the
      pancreas was removed and pancreatic weight, protein content, DNA, amylase and
      chymotrypsin contents were determined. Bombesin produced a significant increase
      (48-475%) of pancreatic weight, tissue contents of protein, DNA, amylase and
      chymotrypsinogen (F = 82, P less than 0.001). When a large dose of bombesin (5
      nmol/kg) was combined with L-364,718 a significant inhibition (up to 70%) of all
      tissue parameters was observed (P less than 0.001). L-364,718 did not affect the
      growth response to a small dose of bombesin (0.6 nmol/kg). Plasma CCK levels 15
      min after a single injection of bombesin (0.6, 1.7 and 5 nmol/kg) were
      significantly increased in response to the 5 nmol/kg dose (2.0 +/- 0.7 to 3.4 +/-
      0.8 pM, F = 6.9, P less than 0.01). No increases of CCK plasma levels were found
      in response to the 0.6 and 1.7 nmol/kg doses of bombesin, corresponding to the
      lack of effects of L-364,718 on growth parameters at these doses. Measuring the
      time-course of CCK plasma levels after a single injection of 5 nmol/kg bombesin
      revealed an increase from basal values of 1.4 +/- 0.3 pM to maximal levels of 3.5
      +/- 0.5 pM after 15 min (F = 7.1, P less than 0.001). Values returned to basal
      after 60 min. These results suggest that low doses of bombesin act directly at
      the acinar cell or through release of non-CCK growth factors whereas high doses
      of bombesin act in part through CCK release.

PMID- 1375382
TI  - Extrinsic control of the release of galanin and VIP from intrinsic nerves of
      isolated, perfused, porcine ileum.
AB  - By immunohistochemistry galanin-like immunoreactivity and vasoactive intestinal
      polypeptide (VIP)-like immunoreactivity were found in nerve cell bodies mostly in
      the submucous plexus and in nerve fibres in the mucosa, submucosa and muscularis
      including the myenteric plexus of the porcine ileum and were found to co-exist in
      most of these structures. Using isolated, perfused porcine ileum we studied the
      release of galanin and VIP in response to electrical stimulation of the mixed
      periarterial nerves or to intraarterial infusions of different neuroactive
      agents. Nerve stimulation (4-10 Hz) inhibited the basal release of galanin and
      VIP from the ileum (to 69 +/- 6 and 62 +/- 6% of basal release). After infusion
      of the alpha-adrenergic blocker, phentolamine, (10(-6) M) electrical stimulation
      increased the release of both galanin and VIP (to 140 +/- 12 and 133 +/- 13% of
      basal output). This increase was abolished by atropine (10(-6) M) and by
      hexamethonium (3.10(-5) M). Infusion of norepinephrine (10(-6) M) inhibited,
      whereas acetylcholine (10(-6) M) stimulated the release of both peptides. The
      effect of the latter was abolished by atropine. The inhibitory effect of nerve
      stimulation was not influenced by atropine. Our results suggest that the galanin-
      and VIP-producing intrinsic neurons receive inhibitory signals by noradrenergic
      nerve fibers and stimulatory signals mediated by cholinergic nerves, possibly via
      a cholinergic interneuron.

PMID- 1375384
TI  - [Sarcoidosis and Whipple's disease: an association or a relationship?].
AB  - Whipple's disease is a rare, systemic disorder characterized by arthritis,
      serositis, diarrhea, malabsorption, lymphadenopathies, weight loss, fever,
      cutaneous hyperpigmentation and central and peripheral nervous system disorders.
      There are approximately 60 published cases with pulmonary involvement, in general
      pleuritis, hilar adenopathies and interstitial affectation. In some occasions,
      sarcoidosis has been diagnosed prior to WD, postulating either a causal
      association between both entities, or a relationship between them, existing in WD
      and initial phase which mimics sarcoidosis. We present a patient diagnosed of
      sarcoidosis who during the evolution of the disease developed gastrointestinal
      symptoms compatible with WD.

PMID- 1375385
TI  - [Indications for surgical treatment of epilepsy].
AB  - The evaluation of drug-resistant epileptics in view of causal surgical epilepsy
      therapy aims at accurate identification of the 'epileptogenic area'. Definition
      of the 'epileptogenic area', which is not synonymous or coexistent with the
      'lesional area', as a positively defined area of seizure onset is obtained
      through the recording and analysis of spontaneous habitual seizures with
      electrodes placed in or close to the presumed epileptogenic brain areas.
      Interictal epileptiform field potentials are important too. Long-term
      intracranial recording techniques include direct intracerebral stereotactic depth
      recording (stereo-electroencephalography, SEEG) and epicortical recordings with
      the use of foramen ovale as well as subdural strip and grid electrodes. The use
      of SEEG requires rigorous criteria, and the anatomy and vessels of the individual
      brain must be known in terms of a stereotactic reference system. Multi-contact
      flexible hollow-core electrodes are stereotactically implanted into strategically
      important targets, according to the evaluation strategy for a given patient. For
      presurgical assessment of potential candidates for selective amygdalo
      hippocampectomy we have developed a less invasive extracerebral recording
      technique. It consists of bilateral insertion of solid four-contact electrodes
      via the foramen ovale, with positioning of the tips of the electrodes at the end
      of the ambient cistern. This technique permits stable and excellent recording
      from the mediobasal limbic structures of both temporal lobes. Personal experience
      with long-term extra-operative intracranial recording and stimulation now
      includes 131 patients evaluated with SEEG and 109 patients evaluated with foramen
      ovale electrodes.

PMID- 1375386
TI  - Combined therapy of thoracic esophageal cancer.
AB  - High rates of esophageal cancer in advanced stages and poor short- and long-term
      results with surgical treatment have led to the use of combined treatment
      regimens. There is, however, no unanimity as to the most effective preoperative
      therapy or the most effective therapeutic tactics. In combined therapy we are in
      favor of strict compliance with the sequence of abdominal exploration,
      radiotherapy, and finally surgery. A differentiated approach according to the
      resectability of the lesion should be maintained. With regard to metastatic
      spread, nodes located in the paracardiac area and lesser omentum must be regarded
      as regional for the thoracic esophagus. Thirty percent of patients with
      metastases to these nodes survive more than 5 years after combined therapy. Based
      on our extensive experience in combined therapy plus an analysis of the
      literature we have formulated the features that will indicate palliative surgery.
      Differentiation between types of operations serves to determine more accurately
      the prognosis and the planning of further therapeutic tactics. With palliative
      surgery adjuvant treatment must always be given.

PMID- 1375387
TI  - Molecular evidence for the expression of Schwann cell markers in human
      neuroblastoma.
AB  - Human neuroblastoma (NB) cell lines have been suggested to represent a model of
      neural crest differentiation. The expression of several Schwann-cell-associated
      antigens was examined by flow cytometry and Northern blot analysis. Variable
      reactivity of the human NB cell lines was found in both the level and pattern of
      reactivity. Retinoic acid treatment of cell line SMS-KAN resulted in a neuron
      like morphological differentiation and a decrease in several of the glial markers
      under study. Similarly, Northern blot analysis illustrated myelin-associated
      glycoprotein expression, and decreased expression of this message with retinoic
      acid treatment was consistent with the neuron-like morphological changes.
      Overall, human NB in vitro was found to be multipotential, but we have shown that
      it is capable of expressing several Schwann cell markers which are modulated
      during induced differentiation.

PMID- 1375388
TI  - Lipoprotein(a) and acute-phase proteins in acute myocardial infarction.
AB  - Lipoprotein(a) (Lp(a)) and the acute-phase proteins, orosomucoid, haptoglobin and
      alpha 1-antitrypsin, were studied in 32 patients with acute myocardial
      infarction. Samples were taken at admission and, after fasting overnight, on the
      following 6 days. In a subgroup of 21 patients total serum cholesterol, high
      density lipoprotein (HDL) cholesterol and triglycerides were also estimated. In a
      linear regression model a significant relation between the relative values of
      Lp(a) and the time in days was obtained (p = 0.001). Compared with the acute
      phase proteins, however, Lp(a) showed a weak increase and the individual
      responses were very variable. There were no correlations between the individual
      changes in Lp(a) and the changes in the acute-phase proteins, but Lp(a) changes
      correlated significantly with the changes in total cholesterol and low-density
      lipoprotein (LDL) cholesterol. It is suggested that the Lp(a) reaction in
      myocardial infarction is linked to the reaction of the lipoproteins. There may
      also be several clinical conditions, including different medications, which
      influence the Lp(a) level.

PMID- 1375389
TI  - Stress-induced gastric ulceration: its aetiology and clinical implications.

PMID- 1375390
TI  - Seroconversion to hepatitis C virus antibodies in patients with acute
      posttransfusion non-A, non-B hepatitis in Sweden with a second generation test.
AB  - 28 patients with posttransfusion non-A, non-B (NANB) hepatitis in Stockholm,
      Sweden, were studied for seroconversion to hepatitis C virus antibodies (anti
      HCV) and time lag to seroconversion by first and second generation tests. 15/28
      patients (54%) seroconverted to anti-HCV with a first generation anti-HCV ELISA
      using C100-3 from the nonstructural (NS) region 4 of the HCV genome and 23 (82%)
      with a second generation anti-HCV ELISA including also antigens from the core and
      NS3 regions of the HCV genome. The mean time from onset of hepatitis to
      seroconversion was 6.1 weeks (0-18 weeks) with the first generation test and 2.3
      weeks (0-7 weeks) with the second generation test. Development of chronic
      hepatitis was noticed in 14/23 (61%) patients who seroconverted to anti-HCV with
      the second generation ELISA and in none of 5 patients with posttransfusion NANB
      hepatitis who did not seroconvert. The inclusion of antigens from the core and
      NS3 regions of the HCV genome has increased the sensitivity of the second
      generation anti-HCV ELISA as compared to the first generation ELISA and also
      shortened the time lag to seroconversion in patients with posttransfusion
      hepatitis C. Patients with posttransfusion NANB hepatitis seroconverting seem
      more prone to develop chronic disease than patients not seroconverting.

PMID- 1375391
TI  - [Percutaneous transhepatic inserted self-expanding metal endoprosthesis in the
      palliative treatment of malignant obstructive jaundice].
AB  - Prospective studies comparing biliary-enteric bypass with implantation of
      endoprostheses in palliation of malignant obstructive jaundice showed no
      significant difference. A new self-expandable metal endoprosthesis was introduced
      to ameliorate the results in terms of early complication and occlusion rate.
      Between December 1988 and April 1991 we treated 35 patients (32 with malignant
      obstructive jaundice) by 50 self-expandable endoprostheses. The implantation was
      successful in 96% of patients. The early complication rate was 37% and the 30-day
      mortality 14%. In 89% of the patients relief of jaundice after 3 months was
      found. Recurrent jaundice and cholangitis occurred in 39%, whereas reoperation
      was necessary in 25%. 16 of 26 patients (61%) with malignant obstructive jaundice
      where alive after an average of 7.5 months. We found no advantage of the self
      expandable endoprostheses compared with conventional plastic stents. Implantation
      of a self-expandable metal endoprosthesis may be an alternative to surgical
      bypass in selected cases. It would be interesting to evaluate the endoscopic
      route of insertion and to compare the results with palliative surgery in
      randomized studies.

PMID- 1375392
TI  - Cystic fibrosis: molecular biology and therapeutic implications.
AB  - Cystic fibrosis is the most common potentially lethal autosomal recessive disease
      of Caucasians, affecting 1 in 2500 newborns. Since the recent identification of
      the gene that is defective in patients with cystic fibrosis, a wealth of
      information about gene structure, the mutational basis of disease, and the
      function of the protein product has been derived. The product of the gene is a
      chloride channel that is regulated by adenosine 3',5'-monophosphate (cyclic AMP)
      dependent protein kinase phosphorylation and that requires binding of adenosine
      triphosphate (ATP) for channel opening. Several new approaches to drug therapy
      for cystic fibrosis are now emerging, and the possibility of successful gene
      therapy by transfer of the normal gene to airway epithelial cells is being
      vigorously pursued.

PMID- 1375393
TI  - Molecular genetics of epidermolysis bullosa.
AB  - Blisters following minor trauma characterize epidermolysis bullosa, a group of
      hereditary diseases of the skin. In the simplex type, epidermal basal cells are
      fragile, and mutations of genes encoding keratin intermediate filament proteins
      underlie that fragility. In the dystrophic types, the causative mutation appears
      to be in the gene encoding type VII collagen, which is the major component of
      anchoring fibrils. These recent findings afford solid evidence that at least one
      function of the cytoskeletal intermediate filament network is the provision of
      mechanical stability and that anchoring fibrils indeed do anchor the epidermis to
      the underlying dermis.

PMID- 1375394
TI  - Initiation of deregulated growth of multipotent progenitor cells by bcr-abl in
      vitro.
AB  - Expression of the bcr-abl oncogene in multipotent progenitor cells (MPPCs) is
      implicated as a key event in the development of chronic myelogenous leukemia.
      Bone marrow enriched for MPPCs was infected with a retrovirus that carried bcr
      abl. The mixed-lineage colonies that resulted were responsive to growth factors
      and could differentiate. These cells later became growth factor-independent but,
      when injected into severe combined immunodeficient mice, were not leukemogenic.
      Thus, the presence of bcr-abl alone does not cause growth factor independence,
      although it initiates a stepwise process. This system may prove useful in the
      study of other oncogenes that cause leukemia.

PMID- 1375395
TI  - Primary structure and functional expression of the beta 1 subunit of the rat
      brain sodium channel.
AB  - Voltage-sensitive sodium channels are responsible for the initiation and
      propagation of the action potential and therefore are important for neuronal
      excitability. Complementary DNA clones encoding the beta 1 subunit of the rat
      brain sodium channel were isolated by a combination of polymerase chain reaction
      and library screening techniques. The deduced primary structure indicates that
      the beta 1 subunit is a 22,851-dalton protein that contains a single putative
      transmembrane domain and four potential extracellular N-linked glycosylation
      sites, consistent with biochemical data. Northern blot analysis reveals a 1,400
      nucleotide messenger RNA in rat brain, heart, skeletal muscle, and spinal cord.
      Coexpression of beta 1 subunits with alpha subunits increases the size of the
      peak sodium current, accelerates its inactivation, and shifts the voltage
      dependence of inactivation to more negative membrane potentials. These results
      indicate that the beta 1 subunit is crucial in the assembly, expression, and
      functional modulation of the heterotrimeric complex of the rat brain sodium
      channel.

PMID- 1375396
TI  - Tyrosine phosphorylation of the vav proto-oncogene product in activated B cells.
AB  - Activation of B lymphocytes by engagement of their immunoglobulin M antigen
      receptors results in phosphorylation of a number of proteins on tyrosine
      residues. One such protein is p95vav, the product of the vav proto-oncogene.
      Tyrosine phosphorylation of p95vav occurred within seconds of immunoglobulin M
      cross-linking and was independent of other events induced during stimulation of B
      cells, such as protein kinase C activation, guanosine triphosphate-binding
      protein signaling, and calcium mobilization. Moreover, engagement of antigen
      receptors induced the rapid (approximately 5 seconds) and transient
      (approximately 60 seconds) association of p95vav with a 70-kilodalton tyrosine
      phosphorylated protein, Vap-1, an interaction mediated by the Src homology 2
      domain of p95vav. These results suggest that the vav proto-oncogene participates
      in the signaling processes that mediate the antigen-induced activation of B
      lymphocytes.

PMID- 1375398
TI  - Role of CD8+ T cells in murine experimental allergic encephalomyelitis.
AB  - The course of experimental allergic encephalomyelitis (EAE), an animal model for
      multiple sclerosis, is affected by immunoregulatory T lymphocytes. When animals
      are immunized with encephalitogenic peptide of myelin basic protein and recover
      from the first episode of EAE, they become resistant to a second induction of
      this disease. Animals depleted of CD8+ T cells by antibody-mediated clearance
      were used to examine the role of CD8+ T cells in EAE. These cells were found to
      be major participants in the resistance to a second induction of EAE but were not
      essential for spontaneous recovery from the first episode of the disease.

PMID- 1375397
TI  - A mutant of TTX-resistant cardiac sodium channels with TTX-sensitive properties.
AB  - The cardiac sodium channel alpha subunit (RHI) is less sensitive to tetrodotoxin
      (TTX) and saxitoxin (STX) and more sensitive to cadmium than brain and skeletal
      muscle (microliter) isoforms. An RHI mutant, with Tyr substituted for Cys at
      position 374 (as in microliter) confers three properties of TTX-sensitive
      channels: (i) greater sensitivity to TTX (730-fold); (ii) lower sensitivity to
      cadmium (28-fold); and (iii) altered additional block by toxin upon repetitive
      stimulation. Thus, the primary determinant of high-affinity TTX-STX binding is a
      critical aromatic residue at position 374, and the interaction may take place
      possibly through an ionized hydrogen bond. This finding requires revision of the
      sodium channel pore structure that has been previously suggested by homology with
      the potassium channel.

PMID- 1375399
TI  - Radiopharmaceuticals for palliation of metastatic osseous lesions: biologic and
      physical background.
AB  - The intimate admixing of bone matrix and bone marrow is a central point in
      devising therapy of metastatic lesions. Since specific modalities are not yet
      available for destroying the malignant cells, treatment is usually palliative.
      The use of stable gallium (Ga-nitrate) and of a diphosphonate
      (aminohydroxypropylidine diphosphonate disodium) as osteoclast inhibitors is
      discussed. The marrow, as well as the matrix, can be affected by external
      radiation. This is also true with bone-seeking radiopharmaceuticals. There is no
      ideal radiopharmaceutical available for treating metastases in bone, but the
      characteristics of several presently available (or proposed) are discussed, and
      possible use of tumor radiation sensitizers or bone marrow protectors is
      mentioned. Difficulties are also encountered in calculating accurate dosimetry.
      Clinical experience is needed to determine a reasonable optimal dose with any
      particular radiopharmaceutical for relief of pain with low bone marrow toxicity.

PMID- 1375400
TI  - Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous
      metastases.
AB  - Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new
      radiopharmaceutical that localizes in skeletal metastases in patients with
      advanced cancer. A single intravenous administration of approximately 34 mCi
      (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable
      patients (77%) following the initial injection, and in 7 of 14 evaluable patients
      (50%) following a second treatment. Patients responding to treatment experienced
      an average decrease in pain of about 60%, with one in five treatments resulting
      in a complete resolution of pain. The only adverse clinical reaction was the
      occurrence after about 10% of the administered doses of a mild, transient
      increase in pain within a few days following injection. Statistically significant
      but clinically unimportant decreases in total white blood cell counts and total
      platelet counts were observed within the first 8 weeks following the injection;
      no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for
      the palliation of painful skeletal metastases.

PMID- 1375401
TI  - Dose-related inhibition of brain and plasma cholinesterase in neonatal and adult
      rats following sublethal organophosphate exposures.
AB  - Developing mammals are markedly more sensitive to acute toxicity from exposure to
      a variety of organophosphorus (OP) pesticides. The present study examined dose
      related inhibition of both brain and plasma cholinesterase activity in neonatal
      and adult rats exposed to sublethal doses of one of three common OP pesticides,
      methyl parathion, parathion and chlorpyrifos. Effective dose 50 (i.e., ED50 or
      dose which would inhibit 50% of the cholinesterase activity) values were
      determined and then correlated with an indicator of acute toxicity, the maximal
      tolerated dose (MTD). It was found that ED50 estimates for both brain and plasma
      cholinesterase correlated highly (r = 0.932-0.992) with previously derived MTD
      values. In no case was there a significant difference between in vivo brain and
      plasma cholinesterase inhibition across doses in neonatal rats was high (r =
      0.962-0.975) but lower in adults (r = 0.700-0.943). The results suggest that in
      vivo inhibitory potency of the three OPs towards either brain or plasma ChE
      activity is highly correlated with sensitivity to acute toxicity in both neonatal
      and adult rats. Additionally, under defined experimental conditions, plasma ChE
      inhibition may be a useful quantitative index for the degree of brain
      cholinesterase inhibition following OP exposures.

PMID- 1375402
TI  - In vitro protein synthesis is affected by the herbicide 2,4-dichlorophenoxyacetic
      acid in Azospirillum brasilense.
AB  - The effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on growth and protein, DNA
      and RNA synthesis of Azospirillum brasilense Cd were studied. At a concentration
      of 1 mM, 2,4-D inhibited cell growth, an effect that was reversed either by
      transferring bacteria to a control (2,4-D-free) medium or to a 2,4-D-treated
      medium supplemented with polyamines. The herbicide also affected in vitro protein
      synthesis, either when Azospirillum brasilense Cd's own cellular mRNA or an
      artificial mRNA was used. This effect was also reversed by the addition of
      polyamines to the 2,4-D-treated medium. Similar results were observed when DNA
      synthesis was studied in synchronous cultures. Taking into account the effects of
      this herbicide on animal cells (V.A. Rivarola and H.F. Balegno, Toxicology, 68
      (1991) 109) we postulate that the mechanism of action of 2,4-D is similar on both
      procaryotic and eucaryotic cells, probably acting through the polyamine
      metabolism.

PMID- 1375403
TI  - Isolated invasive candidal prostatitis.
AB  - Fungal prostatitis is an uncommon entity. Herein we report a case of isolated
      candidal prostatitis in an elderly patient who presented with acute urinary
      retention and was clinically diagnosed as having benign hypertrophy of the
      prostate. Histology of the resected prostate demonstrated invasive prostatic
      involvement by Candida albicans. There was no evidence of systemic involvement by
      Candida. The relevant literature and treatment of isolated Candidal prostatitis
      have been highlighted.

PMID- 1375404
TI  - [Studies of perilymph protein fractions in patients with otosclerosis].
AB  - Studies of the blood serum in 20 patients and perilymph in 10 patients with
      otosclerosis showed stability in concentration of total protein as compared with
      similar control data obtained from cadavers. In this case proteinograms of the
      blood serum and perilymph of patients with otosclerosis exhibit a statistically
      significant decrease in albumin and an increase in globulin fractions mainly at
      the expense of beta- and gamma-globulins with respect to the control. The data
      obtained evidence the presence of immunological disorders in patients with
      otosclerosis.

PMID- 1375405
TI  - Modulation of T-cell reactivity to synthetic peptide analogues of foot-and-mouth
      disease virus in sheep by amino acid substitutions.
AB  - The ability of synthetic peptide analogues of foot-and-mouth disease virus VP1
      capsid protein to induce T-cell proliferation in vitro following immunization of
      sheep with the uncoupled peptides was assessed. Elevated T-cell responses were
      obtained to a 21-residue peptide containing VP1 residues 141-158, and a 40
      residue peptide containing residues 200-213 and 141-158 linked via a diproline
      serine spacer. In contrast, no significant T-cell response was obtained with a 19
      residue peptide containing residues 200-213 alone. In an attempt to engineer T
      cell reactivity to this peptide, a sequence motif found in many peptides
      recognized by human or mouse T-cells was introduced by amino acid substitution.
      Substitution of a glycine or an aspartic acid for an alanine at position 207 in
      the 19-residue peptide resulted in the introduction of two such motifs running
      consecutively. Immunization of sheep with these peptides resulted in significant
      T-cell proliferative responses and elevated antibody responses. Analysis of
      further sequence variants showed that T-cell responsiveness was maintained with
      peptides containing single amino acid changes within these motifs, provided
      position 207 was glycine. The results thus suggest that increased T-cell
      reactivity, might be engineered via sequence manipulation of the 200-213
      component of the 40-residue synthetic peptide. Such an additional T-cell epitope
      in the 40-residue peptide could potentially result in superior neutralizing
      antibody responses directed against the major epitope in residues 141-160 of VP1.

PMID- 1375406
TI  - Borna disease virus-specific antigens. II. The soluble antigen is a protein
      complex.
AB  - Borna disease virus-specific soluble antigen from persistently infected rat
      brains was purified to homogeneity using preparative sodium dodecyl sulphate
      polyacrylamide gel electrophoresis. The soluble antigen is a complex of three
      proteins with apparent molecular weights of 35 kDa, 38 kDa and 24 kDa. The 35/38
      kDa antigen double band was separated into its two components. The 24 kDa protein
      has no common epitopes with the 35/38 kDa protein.

PMID- 1375408
TI  - Dietary methodology workshop for the third National Health and Nutrition
      Examination Survey. March 1986.

PMID- 1375407
TI  - Computer prediction of antigenic and topogenic domains in HSV-1 and HSV-2
      glycoprotein B (gB).
AB  - The envelope glycoprotein B (gB) coded for by the herpes simplex virus type 1
      (HSV-1) UL27 gene is similar to the amino acid (aa) sequence of the gB coded by a
      homologous gene in HSV-2 DNA. The putative antigenic domains in HSV-1 and HSV-2
      gB glycoproteins were analyzed on a comparative basis by suitable computer
      programs, which allowed the prediction of putative antigenic and topogenic
      domains. The computer-derived domains were compared to experimentally reported
      antigenic domains in HSV-1 gB glycoprotein. The computer-predicted antigenic
      domains in the HSV-1 gB glycoprotein matched well with the reported
      experimentally derived antigenic domains. The aa sequence of antigenic domain 1
      was noted to resemble the amino acid sequence in ApoE that is involved in the
      attachment of this protein to LDL receptors. The clusters of hydrophobic aa
      domains are conserved in the two viral glycoproteins and are signals for transfer
      of the viral proteins through the cellular membrane.

PMID- 1375409
TI  - Measuring dietary patterns in surveys.
AB  - This paper reviews the strengths, weaknesses, and limits to interpretation of
      dietary intake methods used in national nutrition surveys, including per capita
      consumption of food and nutrients and the 24-hour recall. These dietary
      assessment methods make up but one of five categories of nutritional assessment
      techniques. The other four are body measurements, hematological and biochemical
      tests, medical examination for the presence of clinical signs of deficiency or
      toxicity, and medical history. No one method alone is sufficient for assessing
      the nutritional status of individuals or groups. In the hypothesis-generating
      phases of research on diet and cardiovascular diseases and diet and cancer,
      correlations of per capita availability of food and nutrients with mortality from
      these diseases in several countries proved useful. However, the approach is
      limited to the extent that similar data are available from several other
      countries and that the association observed is true and not spurious. The 24-hour
      recall method has proved to provide accurate and reproducible estimates of the
      mean intakes of population groups, but multiple-day information is necessary for
      characterizing an individual's usual nutrient intake. Food frequency
      questionnaires are useful when one is interested in food rather than nutrient
      consumption of individuals or groups. The 24-hour recall, food diary, and food
      frequency methods can be used to develop a descriptive epidemiology of food
      intake within U.S. population groups with specified fitness and activity
      characteristics or to monitor the prevalence of dietary risk factors within the
      population. They are limited to the extent that food composition data are
      available. When selecting a dietary assessment method to be used in a nutrition
      survey, three points must be kept in mind: Practicality in terms of respondent
      burden and analysis resources, reliability, and validity.

PMID- 1375410
TI  - Dietary assessment issues related to cancer for NHANES III.

PMID- 1375411
TI  - Statistical issues related to the design of dietary survey methodology for NHANES
      III.

PMID- 1375413
TI  - Dietary methodology issues related to energy balance measurement for NHANES III.

PMID- 1375412
TI  - Dietary methods in cardiovascular disease critique.
AB  - It is planned that a wide variety of questions related to nutrient intake and
      cardiovascular disease will be addressed in NHANES III. Given the scope of these
      questions and the number of different types of designs that may be utilized-
      cross-sectional, cohort, and case control--several different dietary
      methodologies will probably be needed within NHANES III. Assessment and ranking
      of current intake is a primary objective to the overall NHANES III design. The 24
      hour recall will provide this assessment and maintain comparability with the
      previous extensive NHANES. In many instances, however, information on usual
      intake or past intake will be necessary to better elucidate a nutrient-disease
      relationship, either because of temporal exposure concerns or because of the
      variability of the nutrient intake. A food history or quantitative frequency
      method for the specific nutrient(s) would best address these needs. Information
      on specific foods or other diet constituents (such as fish, dairy foods, alcohol,
      or water intake) in addition to nutrient levels will be of interest not only for
      cardiovascular disease but, with some food items, for cancer and osteoporosis as
      well. A history or quantitative frequency method would be appropriate for this
      purpose. The question of serial and multiple measures needs to be addressed. For
      adequate classification of individuals, several nonconsecutive measures would be
      most appropriate. The actual number of measures would be determined by the
      estimate of the most acceptable reduction in variance that could be achieved with
      multiple measures, balanced by the feasibility and cost of such measures. The use
      of multiple measures would necessitate the use of alternative interview
      techniques, most likely by telephone. It is clear that, if this type of
      methodology is adopted, further validation and extensive pretesting would need to
      be conducted. A subsample approach could also be utilized. Automated coding of
      dietary data and computer-prompted immediate data entry interview techniques may
      facilitate the use of these dietary data collection methods. Whichever methods
      are utilized, standardization of the coding procedures and additions to the
      nutrient data base, particularly for sodium, are essential. Finally, there is
      considerable interest in evaluating any deleterious effects of dietary
      modification on health and mortality outcome. For example, there is concern that
      a fat-modified diet may increase cancer mortality in some or that a low-sodium
      diet may be unpalatable and lead to a lowered dietary intake and potential
      nutrient deficiencies. It would be useful in this regard for NHANES III to be
      able to ascertain if altered dietary levels were due to self-selected dietary
      practices, to prescription of a therapeutic diet, or to a disease state or
      illness that lowered overall food intake.

PMID- 1375414
TI  - Critique of studies of the relationship between diet and osteoporosis.

PMID- 1375415
TI  - Dietary methodologies for food and nutrition monitoring.

PMID- 1375416
TI  - Working group consensus statements.

PMID- 1375417
TI  - Dietary methodology considerations for NHANES III.

PMID- 1375418
TI  - Process and rationale for selecting dietary methods for NHANES III.

PMID- 1375419
TI  - Breast reconstruction following mastectomy with pedicled and free TRAM flaps.
AB  - The authors present a group of nine patients after mastectomy. Breast
      reconstruction was performed by transposition (3) or by free transplantation (6)
      of a TRAM flap. Based on a review of literary reports, and on their own
      experience, the authors consider this procedure to be a reliable and effective
      method of breast reconstruction.

PMID- 1375420
TI  - Experimental substantiation of allogenic tendon tissue transplantation.
AB  - Substantiation of transplantation of tendon allografts treated with a new
      solution showing both sterilizing and preservatory effects was provided in
      experiments on 84 dogs. The solution prepared on the basis of 0.1% formaldehyde
      with the addition of dimethyl sulphoxide, monomycin and prednisolone (FDMP) shows
      a high antimicrobial activity, preserves the structure of the tendons and their
      elasticity. In their duration, the processes of reconstruction of allografts
      preserved in FDMP are very similar to autotransplants. Clinical application of
      preserved tendons on repairing defects in 418 patients proved the method to be
      highly effective.

PMID- 1375421
TI  - The antecubito-radial flap for the repair of forearm defect.
AB  - The antecubito-radial flap based on the inferior cubital artery via radial artery
      had been transposed to the forearm defect. Through the flow of this flap is
      normal at cubital and that of radial vessels retrograde, good results have been
      obtained. Advantage of this flap was discussed in relation to the radial forearm
      and the antecubital flap.

PMID- 1375422
TI  - Functional and aesthetic results of treatment of thermal injury.
AB  - The authors report the results of treatment and a one year follow-up study of
      1000 burned patients (1982-1986). Of 482 patients with superficial and deep
      dermal burns 246 patients had been operated (135 of 168 patients with deep
      burns). Impairment of function has been observed in 52 and complete disability in
      7 cases. The authors suggest planned collecting of data on the remaining
      complications following thermal injury.

PMID- 1375423
TI  - Controversy concerning the deadline for surgical interventions of a nose in
      children.
AB  - The authors try to explain when the surgeons can operate the nose of a child
      patient. Sixty years ago the limit borderline age was established. This
      borderline was 16 years for girls and 18 years for boys. Some plastic surgeons
      published the results of corrective operations in children between the age 5-16
      years, because of breaking of the nasal bones, past diseases and inborn facial
      defects. No disturbances have been found of cartilages and bones of nose and the
      jaw area.

PMID- 1375424
TI  - Repair of a vaginal defect with a musculocutaneous flap.
AB  - The authors present a case report dealing with a successful treatment of an
      infected chronic defect of vaginal region. The surgical treatment consisted in
      the use of a transposition of a pedicled gracilis musculocutaneous flap. The
      described procedure could prove useful at departments where transpositions of
      free flaps are not performed routinely.

PMID- 1375425
TI  - Reconstruction of the penis in transsexual patients.
AB  - In the article, the authors offer a review of the modalities available for
      phalloplasty in transsexual patients. The classic methods for multi-stage
      transplantation of tubulized flaps in the lumbar and inguinal regions, in mid
      thigh as well as current methods for one-stage reconstruction are discussed. The
      paper contains the case report of a transsexual patient undergoing one-stage
      reconstruction of the penis using m. rectus abdominis with the inferior pedicle,
      urethral reconstruction by a skin graft from simultaneous mastectomy with a free
      forearm flap covering the muscle. The paper examines the pros and cons of each
      method for reconstruction.

PMID- 1375426
TI  - Meatoplasty with reconstruction of the foreskin. A procedure for anterior
      hypospadias.
AB  - There is a growing awareness of normal outlook of the male genitalia. Described
      technique of meatoplasty with reconstruction of the foreskin is a relatively
      simple but safe method with satisfactory results, both functional and cosmetic,
      in cases of glandular, coronal and anterior penile hypospadias, applicable in the
      absence of fibrous chordee.

PMID- 1375427
TI  - Mast cells in oral erythema multiforme.
AB  - We compared the number of mast cells in erythema multiforme lesions, in
      clinically healthy mucosa between the EM attacks and in healthy mucosa from
      healthy volunteers. The mast cell count in patients with erythema multiforme was
      numerically higher than in healthy controls, but the differences were not
      statistically significant. In erythema multiforme lesions the mast cell count was
      low in the intensely inflamed superficial lamina propria, but high in normal
      appearing mucosa between the attacks suggesting local mast cell degranulation in
      the most intensely inflamed areas.

PMID- 1375428
TI  - [Renal cholesteatoma: keratin accumulation tumor].
AB  - Presentation of 6 cases of renal cholesteatoma in 4 male and 2 female patients
      ranging between 30 and 67 years of age. The most consistent clinical data was a
      history of relapsing nephritic colic of long-evolution. The average time to
      diagnose was 19 years. In 50% cases an association to malignant neoplastic
      pathology was found. The clinical diagnosis was based on the urography and the
      histopathological examination of the material passed with the urine. Renal
      exeresis was performed in 5 cases. One was treated in a conservative fashion.
      Also the etiology causes, diagnostic procedure and other therapeutic
      possibilities were reviewed.

PMID- 1375429
TI  - [Relationship between prolactin and nodular hyperplasia and carcinoma of the
      prostate].

PMID- 1375430
TI  - Topical nasal decongestants.

PMID- 1375431
TI  - Cutaneous T-cell lymphoma presenting with diffuse lymphomatous infiltration of
      the peripheral nerves: response to combination chemotherapy.
AB  - A patient with nonepidermotropic cutaneous T-cell lymphoma presented with severe
      diffuse peripheral neuropathy that was the result of lymphomatous infiltration of
      the peripheral nervous system. There was no other evidence of systemic disease.
      The diagnosis was delayed because of the unusual presentation. A peripheral nerve
      biopsy was instrumental in establishing the etiology of the neuropathy. The
      patient achieved complete clinical remission with combination chemotherapy.

PMID- 1375432
TI  - cAMP-activated Cl channels in CFTR-transfected cystic fibrosis pancreatic
      epithelial cells.
AB  - Retrovirus-mediated transfection of cDNA for the cystic fibrosis (CF) gene into
      the CF pancreatic cell line, CFPAC-1, confers adenosine 3',5'-cyclic
      monophosphate (cAMP)-dependent regulation of Cl conductance. We used patch-clamp
      techniques to identify the single-channel basis of this conductance pathway and
      to study its properties. Forskolin or cAMP activated Cl channels with a
      conductance of 9 +/- 1 pS in 26 of 62 cell-attached patches of cystic fibrosis
      transmembrane conductance regulator (CFTR)-transfected CFPAC-1 cells. The current
      voltage (I-V) relation showed slight outward rectification (chord conductance of
      10 +/- 2 pS at +80 mV vs. 7 +/- 1 pS at -80mV) with high Cl concentrations (170
      mM) in the pipette solution. Channel kinetics were voltage sensitive, with longer
      openings at positive clamp voltages. Channel properties were unaffected by the
      substitution of N-methyl-D-glucamine for pipette Na or by the addition of
      disulfonic stilbenes (100 microM DNDS or DIDS) to the pipette. The channels
      usually inactivated within seconds of patch excision, but in three of nine
      patches, activity could be maintained by addition of the catalytic subunit of
      protein kinase A and ATP. With equal Cl concentrations on both membrane surfaces,
      the single-channel I-V relation was linear, suggesting that the outward
      rectification of the cell-attached channel is due to a pipette-to-cell Cl
      gradient. Anion substitution on the extracellular side of the membrane indicates
      a halide permselectivity of Br approximately Cl greater than I.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1375433
TI  - Immunocytochemical and functional characterization of Na+ conductance in adult
      alveolar pneumocytes.
AB  - The purpose of this study was to document the existence, assess the spatial
      localization, and characterize some of the transport properties of proteins
      antigenically related to epithelial Na+ channels in freshly isolated rabbit and
      rat alveolar type II (ATII) cells. ATII cells, isolated by elastase digestion of
      lung tissue and purified by density-gradient centrifugation, were incubated with
      polyclonal antibodies raised against Na+ channel protein purified from beef
      kidney papilla (NaAb), followed by a secondary antibody (goat antirabbit
      immunoglobulin G conjugated to fluorescein isothiocyanate). Rat ATII cells
      exhibited specific staining with NaAb at the level of the plasma membrane, which,
      in most cells, colocalized with that of the lectin Maclura pomiferra agglutinin,
      an apical surface marker. In Western blots, NaAb specifically recognized a 135 +/
      10-kDa protein in rat ATII membrane vesicles. When patch clamped in the whole
      cell mode using symmetrical solutions (150 mM Na+ glutamate), ATII cells
      exhibited outwardly rectified Na+ currents that were diminished by amiloride (10
      100 microM) instilled into the bath solution. Ion substitution studies showed
      that the conductive pathways were three times more permeable to Na+ than K+.
      Amiloride, benzamil, and 5-(N-ethyl-N-isopropyl)-2',4'-amiloride were equally
      effective in diminishing 22Na+ flux into rabbit and rat ATII cells (45%
      inhibition at 100 microM, with IC50 of approximately 1 microM for all
      inhibitors). Tetraethylammonium chloride (10 mM) or BaCl2 (2 mM), well-known K+
      channel blockers, had no effect on 22Na+ uptake. These results indicate that ATII
      cells express an amiloride-sensitive Na+ conductance, probably a channel, with a
      lower affinity for amiloride and its structural analogues than the well
      established amiloride-sensitive Na+ channels found in bovine renal papila and
      cultured amphibian A6 kidney cells.

PMID- 1375434
TI  - Characterization of a delayed rectifier potassium current in chicken growth plate
      chondrocytes.
AB  - With the use of the whole cell arrangement of the patch-clamp technique, an
      outward-directed time-dependent potassium current was identified in cultured
      chicken growth plate chondrocytes. This delayed rectifier potassium current (IK)
      activated with a sigmoidal time course during voltage steps to potentials
      positive to -40 mV. The half-maximal voltage required for current activation was
      determined to be -8 mV. The reversal potential (Erev) for IK, measured using
      deactivating tail currents, was -72 mV in the presence of 140 mM internal and 5
      mM external [K+] solutions. Changes in external [K+] caused Erev to shift in a
      manner expected for a potassium-selective channel. In addition, increasing
      external [K+] from 5 to 50 mM caused the slope conductance of the tail currents
      to increase twofold. The chondrocyte IK was inhibited by the potassium-channel
      blocker 4-aminopyridine (4-AP) at concentrations of 0.5-4 mM and by the scorpion
      venom toxin charybdotoxin (CTX; 10 nM) but was unaffected by 10 mM
      tetraethylammonium (TEA). Addition of 20 microM ZnCl2 reduced IK in a voltage
      dependent manner with the greatest inhibition found to occur at potentials near
      the threshold for current activation. Reduction of IK by ZnCl2 was accompanied by
      a slowing in the kinetics of IK activation. On the basis of the gating and
      pharmacological properties of this current, it is suggested that the chondrocyte
      channel belongs to a superfamily of K+ channels found in bone and immune system
      cells. The chondrocyte K+ channel may contribute to the unusually high [K+] found
      in the extracellular fluid of growth plate cartilage.

PMID- 1375435
TI  - Pyruvate carboxylase in genetic obesity.
AB  - Immunoblotting and protein microsequencing were used to identify several
      adipocyte proteins expressed in an obesity-related fashion in the Zucker rat. One
      of these was a 116-kDa particulate protein (p116). The p116 levels in adipocytes
      from 5- to 7-wk-old obese Zucker rats were two- to fivefold higher on a per
      milligram of protein basis than levels in lean animals and decreased after the
      induction of streptozotocin-induced diabetes mellitus. This suggests the change
      may be related to the actions of insulin. Hepatic levels of p116 did not change.
      The p116 was purified to homogeneity from obese Zucker rat adipocytes, and
      polyclonal antisera were prepared against the purified protein in rabbits.
      Microanalysis of electroblotted p116 proteolytic fragments suggested that p116
      was pyruvate carboxylase (PC). Other evidence that p116 was PC included the
      following: 1) p116 contained biotin, 2) p116 in particulate subcellular fractions
      was soluble after freeze-lysis, 3) antibodies to p116 reacted with purified
      hepatic PC, 4) p116 and purified hepatic PC had identical pI and relative
      molecular weight values, and 5) similar changes were detected in adipocyte p116
      and PC enzyme activity during obesity and after the induction of streptozotocin
      induced diabetes mellitus. Increased adipose tissue PC probably contributes to
      the increased lipogenic capacity of young obese Zucker rat adipocytes.

PMID- 1375436
TI  - Effect of prolactin on 2-deoxyglucose uptake in mouse mammary gland explants.
AB  - These studies were carried out to explore the possible effect of prolactin (PRL)
      on glucose uptake into culture mammary gland explants derived from 12- to 14-day
      pregnant mice. PRL was found to stimulate an increased rate of uptake of a
      nonmetabolized glucose analogue, 2-[3H]deoxyglucose, into cultured mammary
      tissues. The onset of this response was 16 h after the addition of PRL, and the
      response persisted for at least 24 h. A similar temporal response was observed
      when the PRL stimulation of [14C]glucose oxidation to 14CO2 was determined. The
      lowest PRL concentration that elicited a stimulation of 2-deoxyglucose uptake was
      20 ng/ml, and a maximum response occurred with PRL at a concentration of 250
      ng/ml. Ongoing protein synthesis appears to be essential for PRL to express its
      effect on 2-deoxyglucose transport since cyclohexamide, puromycin, and
      actinomycin D abolished the PRL response. It is also apparent that the PRL
      stimulation of 2-deoxyglucose involves activation of a specific carrier-mediated
      uptake transport system, since the rate of uptake of L-glucose into mouse mammary
      gland explants was unaffected by PRL.

PMID- 1375437
TI  - Liver releases galanin during sympathetic nerve stimulation.
AB  - To determine whether the gut or liver releases galanin during sympathetic neural
      activation, we performed bilateral thoracic splanchnic nerve stimulation (BTSNS)
      in halothane-anesthetized dogs. Using experimentally determined galanin
      extraction rates of 60% for gut and no extraction by liver, calculations
      demonstrated a minor increase in gut spillover during BTSNS (delta = +4.8 +/- 1.8
      pmol/min), whereas liver spillover of galanin-like immunoreactivity (GLIR)
      increased markedly (delta = +27.9 +/- 9.5 pmol/min). To confirm the finding of
      liver galanin release, GLIR was measured in femoral artery, portal vein, and
      hepatic vein during hepatic nerve stimulation (HNS). GLIR spillover from gut was
      not increased by HNS (delta = +1.9 +/- 6.3 pmol/min). In contrast, liver GLIR
      spillover was greatly increased during HNS (delta = +53.3 +/- 16.4 pmol/min).
      Extracts of canine liver contained 2.7 +/- 0.4 pmol GLIR/g tissue. We conclude
      that, despite the known significant galanin content of the gut, little galanin is
      released from this organ during sympathetic activation. In contrast, the liver,
      heretofore not described to contain galanin, contains and releases significant
      amounts of the peptide during sympathetic activation.

PMID- 1375438
TI  - Calcium and potassium currents in canine gastric smooth muscle cells.
AB  - Membrane ionic currents were recorded in single smooth muscle cells dissociated
      from circular muscle of dog stomach (corpus region). When studied under voltage
      clamp with K+ in the patch electrode, depolarization to potentials more positive
      than -40 mV, from a holding potential of -70 or -80 mV, evoked transient inward
      current followed by outward current. Evidence that the outward current was due to
      K+ came from analysis of deactivation tail currents, which reversed direction
      close to the K+ equilibrium potential. In addition, the outward current was
      reduced by tetraethylammonium (TEA, 1-5 mM) applied to the external surface of
      cells. The Ca(2+)-channel blocker Cd2+ blocked the inward current and also
      reduced outward current, suggesting Ca(2+)-activated K+ current contributed to
      the outward current. The voltage-activated inward current was studied in
      isolation with Cs+ and TEA in the recording electrode to block K+ current. In
      standard bathing solution containing 2.5 mM Ca2+, the inward current activated
      between -50 and -40 mV, with peak inward current at +10 mV. The depolarization
      activated inward current was blocked by nifedipine and enhanced by BAY K 8644,
      providing evidence that it was Ca2+ current. The Ca2+ current showed transient
      and sustained components, both of which showed similar voltage activation and
      inactivation ranges. The half-inactivation potential was approximately -37 mV.
      These results provide evidence that smooth muscle cells from the canine gastric
      corpus possess K+ and Ca2+ channels. Based on the voltage dependence of
      activation and inactivation and sensitivity to dihydropyridines, L-type Ca2+
      channels predominate in canine gastric corpus smooth muscle.

PMID- 1375439
TI  - Regulation of hepatic glycogenolysis and vasoconstriction during antigen-induced
      anaphylaxis.
AB  - Effects of sensitizing antigen (ovalbumin) on various physiological and hepatic
      parameters were investigated in sensitized rats and isolated perfused livers
      derived from sensitized rats. Administration of ovalbumin (500 micrograms) to the
      portal venous circulation of sensitized but not nonsensitized rats resulted in a
      rapid and sustained decrease in systemic arterial pressure, characteristic of
      antigen-induced anaphylaxis, and pronounced increases in hepatic portal pressure
      and blood glucose concentration. These antigen-mediated alterations were similar
      to those observed in response to platelet-activating factor (PAF) (0.1
      micrograms/kg) administration to rats and were inhibited significantly by
      specific PAF receptor antagonist WEB 2086 (250 micrograms/kg). Infusion of
      ovalbumin (3.8 micrograms/ml) into isolated perfused livers derived from
      sensitized rats resulted in significant increases in hepatic glucose output and
      portal pressure and decreases in oxygen consumption, as observed in response to
      PAF (0.28 nM) infusion into perfused livers. These hepatic responses to ovalbumin
      were antigen specific and were not observed in nonsensitized rat perfused livers.
      Hemodynamic and glycogenolytic responses to ovalbumin in perfused livers were
      inhibited significantly but less effectively than similar responses to PAF by
      infusion of WEB 2086 (500 nM) into livers. Coinfusion of indomethacin (2.8
      microM) and nordihydroguariatic acid (1 microM) with WEB 2086 (500 nM) into
      perfused livers inhibited further hemodynamic but not glycogenolytic responses to
      ovalbumin. Infusion of nitric oxide (34 microM) into sensitized rat perfused
      livers prevented the hemodynamic and glycogenolytic responses to both ovalbumin
      and PAF. These observations provide evidence that hepatic glycogenolysis and
      vasoconstriction are stimulated during antigen-induced anaphylaxis and suggest
      that these responses are mediated in part by PAF.

PMID- 1375440
TI  - Bovine tracheal serous cell secretion: role of cAMP and cAMP-dependent protein
      kinase.
AB  - The role of adenosine 3',5'-cyclic monophosphate (cAMP) and protein
      phosphorylation during beta-adrenergic receptor stimulation of bovine tracheal
      gland serous cells was investigated in vitro. Isoproterenol, a beta-adrenergic
      agonist, increased the secretion of 35S-labeled molecules. Intracellular cAMP
      levels were increased within 1 min after stimulation of bovine tracheal gland
      serous cells with isoproterenol. The dose-response relationship for isoproterenol
      stimulated generation of cAMP correlated with the dose-response relationship for
      isoproterenol-stimulated secretion of 35S-labeled molecules. The
      phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine potentiated both
      isoproterenol-evoked secretion of 35S-labeled molecules and the production of
      intracellular cAMP, and the beta-adrenergic receptor antagonist propranolol
      completely blocked both effects. The secretory response of the cells to
      isoproterenol could be mimicked by the cAMP analogues 8-bromoadenosine 3',5'
      cyclic monophosphate and dibutyryl adenosine 3',5'-cyclic monophosphate. Activity
      of cAMP-dependent kinase was measured in soluble and particulate cell extracts.
      cAMP effected the state of phosphorylation of proteins associated with the
      soluble but not the particulate fraction. These studies are consistent with the
      hypothesis that beta-adrenergic stimulation of secretion from bovine tracheal
      gland serous cells occurs via a cAMP-mediated pathway and that one of the
      molecular events in this pathway is cAMP-dependent protein phosphorylation.

PMID- 1375441
TI  - Evidence for a kynurenate-insensitive glutamate receptor in nucleus tractus
      solitarii.
AB  - Previous studies have shown that pharmacological blockade of ionotropic
      excitatory amino acid (EAA) receptors in the nucleus tractus solitarii (NTS) with
      kynurenate (Kyn) abolishes baroreceptor reflexes but fails to affect
      cardiovascular responses evoked by microinjections of L-glutamate (Glu) into the
      NTS. These observations have raised doubts as to whether Glu is a
      neurotransmitter of baroreceptor information in the NTS because the
      pharmacological actions of exogenously administered Glu are not identical to
      those of the neurotransmitter released in the NTS coincident with baroreceptor
      activation. One possible explanation for these results is that exogenously
      administered Glu might act at receptors that are not blocked by Kyn and are not
      accessible to synaptically released Glu in the NTS baroreflex pathway. The
      purpose of this study was to determine if Kyn-insensitive Glu receptors are
      present in the NTS. One candidate for this Kyn-insensitive receptor is the
      metabotropic EAA receptor that is selectively activated by trans-DL-1-amino-1,3
      cyclopentane-dicarboxylic acid (ACPD). Microinjections of ACPD into the NTS of
      anesthetized rats produced dose-related depressor responses that were not reduced
      by Kyn or by pretreatment with the putative ACPD receptor antagonist L-2-amino-3
      phosphonopropionate (L-AP-3). Similarly, depressor responses produced by Glu also
      were not affected by Kyn or by L-AP-3. These data demonstrate the presence of a
      Kyn-insensitive Glu receptor in the NTS. Moreover, they suggest that the failure
      of Kyn to reduce cardiovascular responses evoked by Glu injections into the NTS
      can be explained by an action of Glu at Kyn-insensitive ACPD receptors.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1375442
TI  - Kinetics of endotoxin-induced acute-phase protein gene expression and its
      modulation by TNF-alpha monoclonal antibody.
AB  - The kinetics of cytokine release and acute-phase protein gene expression in liver
      were investigated in rats receiving a single intraperitoneal bolus dose of
      Escherichia coli lipopolysaccharide (LPS). Transient elevation of plasma tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were detected. Hepatic
      messenger RNAs for two acute-phase proteins, alpha 1-acid glycoprotein and alpha
      2-macroglobulin, were measured by Northern blotting and were found to increase to
      a maximum at 24 h, returning to normal by 72 h; plasma concentrations showed a
      slower but more sustained rise. For albumin, hepatic mRNA was reduced, being
      minimum at 24 h with a similar but more prolonged fall in plasma concentration.
      Pretreatment of rats with TNF-alpha monoclonal antibody 4 h before LPS
      ameliorated weight loss and anorexia, partially suppressed the rise in IL-6 and
      reduced the increase in hepatic mRNA and plasma concentrations of alpha 1-acid
      glycoprotein and alpha 2-macroglobulin. For albumin, however, such pretreatment
      had no effect on the fall in either hepatic mRNA or plasma concentration. Thus we
      have defined an in vivo role of TNF-alpha in the control of endotoxin-induced
      acute-phase protein generation.

PMID- 1375443
TI  - Alpha 2-adrenergic regulation of galanin and norepinephrine release from canine
      pancreas.
AB  - We found previously that electrical stimulation of the mixed autonomic pancreatic
      nerves (MPNS) is anesthesized dogs elicits marked and rapid increases of
      pancreatic output of both norepinephrine (NE) and galanin, and on that basis
      hypothesized a role for galanin as a sympathetic cotransmitter in the endocrine
      pancreas. In the present study, direct evidence was sought for the co-release of
      galanin and NE from canine pancreas by determining whether pancreatic galanin
      output is subject to modulation by presynaptic alpha 2-adrenergic mechanisms as
      has been established for NE. During MPNS (8 Hz, 1 ms, 10 mA, 10 min) in
      anesthesized dogs, both pancreatic NE and galanin outflow were increased with
      similar temporal patterns during consecutive stimulations. Blockade of
      presynaptic alpha 2-adrenoceptors with yohimbine increased and stimulation of
      presynaptic alpha 2-adrenoceptors with clonidine reduced NE and galanin outflow.
      Over all experiments, pancreatic spillover of galanin was highly correlated with
      that of NE. It is concluded that presynaptic alpha 2-adrenergic mechanisms
      modulate not only NE but also pancreatic galanin release, suggesting that galanin
      is co-released with NE from noradrenergic nerves in the endocrine pancreas.

PMID- 1375444
TI  - Development of myelination in the human fetal and infant cerebrum: a myelin basic
      protein immunohistochemical study.
AB  - The early development of myelination was studied by means of myelin basic protein
      (MBP) and luxol fast blue (LFB) stainings of large sections of the cerebral
      hemispheres. Myelination first occurs in the globus pallidus, pallidothalamic
      fibers of the posterior internal capsule and the thalamus at 25 weeks, which may
      be related to the cellular maturation in the globus pallidus and thalamus. Then
      myelination is observed in the striatum, and precentral and postcentral gyri at
      35 weeks, and the anterior internal capsule and optic radiation at 37 weeks.
      Immunoreactivity with MBP is observed earlier and more strongly in the early
      myelination period than that with LFB. Thus, MBP may play an important role in
      myelination and its delay. The macroscopic positivity as to MBP as well as LFB
      staining may be related to the development of high signal intensity observed in a
      T1-weighted magnetic resonance imaging, which was observed 1 to 3 months after
      the first microscopic appearance of myelin.

PMID- 1375445
TI  - A mild juvenile variant of type IV glycogenosis.
AB  - The mild juvenile form of type IV glycogenosis, confirmed by a profound
      deficiency of the brancher enzyme in tissue specimens is reported from three
      Turkish male siblings who, foremost, suffered from chronic progressive myopathy.
      Muscle fibers contained polyglucosan inclusions of typical fine structure i.e. a
      mixture of granular and filamentous glycogen. They reacted strongly for
      myophosphorylase, but were resistant to diastase. These inclusions were
      ubiquitinated and reacted with antibody KM-279 which previously has been shown to
      bind to Lafora bodies, corpora amylacea and polyglucosan material in hepatic and
      cardiac cells of type IV glycogenosis as well as polyglucosan body myopathy
      without brancher enzyme deficiency. Our findings confirm that although rate, a
      mild form of type IV glycogenosis is marked by polyglucosan inclusion not only in
      myofibers, but also in smooth muscle and sweat gland epithelial cells. This
      further implies that when polyglucosan inclusions are observed within myofibers
      it is mandatory to examine the muscle tissue for brancher enzyme activity since
      the brancher enzyme activities in circulating erythrocytes and leucocytes were
      normal in all three affected siblings and their parents. Therefore, it can be
      concluded that the patients reported on here represent a variant form of type IV
      glycogenosis, in which the defect is limited to muscle tissue. This further
      indicates that there are several different types of type IV glycogenosis with
      variable clinical manifestations.

PMID- 1375446
TI  - Urinary 5-hydroxytryptophol: a possible marker of recent alcohol consumption.
AB  - Urinary 5-hydroxytryptophol (5-HTOL) is currently being evaluated as a marker of
      recent alcohol consumption. To compensate for urinary dilution, the molar ratio
      between 5-HTOL and 5-hydroxyindole-3-acetic acid (5-HIAA) is used. The 5-HTOL/5
      HIAA ratio showed a satisfactory degree of individual stability when it was
      followed in a group of teetotallers for 1 month. The mean value of 5-HTOL/5-HIAA
      in a group of 69 persons abstaining from alcohol was 7.6 (pmoles 5-HTOL/nmoles 5
      HIAA). Ninety-seven percent had values ranging from 4 to 17, with no value
      exceeding 20. A group of healthy volunteers were tested 12 hr after alcohol
      consumption and showed a dose-dependent and statistically significant elevation
      in the 5-HTOL/5-HIAA ratio. Four regular alcohol consumers who were followed
      during a period of 3 months of drinking had elevated values of the 5-HTOL/5-HIAA
      ratio in 60% of their urine samples. The present study indicates that urinary 5
      HTOL/5-HIAA is a sensitive and reliable marker of recent alcohol consumption. We
      propose that a 5-HTOL/5-HIAA ratio greater than 20 (pmoles/nmoles) can be used to
      indicate recent alcohol consumption. This limit gives a low frequency of false
      positives; the statistical probability of having a value greater than 20 during
      abstinence from alcohol was calculated to be less than 0.001.

PMID- 1375447
TI  - Effects of ethanol on DNA, RNA, and protein synthesis in rat astrocyte cultures.
AB  - Brain growth retardation is a major feature of the fetal alcohol syndrome (FAS).
      Insulin and insulin-like growth factors (IGF-I and IGF-II) exert significant
      growth-promoting effects on the central nervous system (CNS). The present study
      examined the effects of ethanol and its interactions with growth factors on the
      incorporation of labeled precursors into DNA, RNA, and protein in primary
      astrocyte cultures prepared from term fetal rats. Cultures were exposed to
      ethanol for 18hr in serum-free medium before measuring nucleoside or amino acid
      incorporation into acid-precipitable cell constituents. Under basal conditions,
      ethanol induced dose-dependent changes in the rates of incorporation of tritiated
      thymidine, uridine, and valine. The fraction of the total thymidine uptake that
      was incorporated into DNA was reduced in the presence of 100 and 200 mM ethanol.
      Effects on uridine and valine incorporation paralleled cell uptake. Insulin (10(
      6) M) and IGF-I (10(-9) M) increased (p less than 0.01) incorporation of
      radiolabeled thymidine, uridine, and valine. Analysis of variance indicated
      highly significant interactions between ethanol and the effects of growth factors
      on incorporation of both nucleosides and valine. Interference with the action of
      neurotrophic factors may be a significant factor in fetal brain growth
      retardation associated with maternal ethanol ingestion.

PMID- 1375448
TI  - Effects of multiple doses of isoprinosine on Echinococcus multilocularis
      metacestodes.
AB  - Isoprinosine was given at daily doses of 0.5, 1, 2, and 4 g kg-1 of body weight
      to jirds that were infected for 3 months with Echinococcus multilocularis
      metacestodes. The effects of the different drug doses on metacestodes were
      studied by transmission electron microscopy and biochemical methods. At lower
      doses, increases in uric acid and adenosine deaminase activity were noted. At 4 g
      kg-1 of body weight, marked ultrastructural damage with metabolic perturbations
      was observed.

PMID- 1375449
TI  - Correlation between regulation of mecA transcription and expression of
      methicillin resistance in staphylococci.
AB  - Total RNA was used to study the effect of penicillinase plasmid pI524 and of
      mecR, the regulatory region located on the methicillin resistance determinant
      (mec), on the expression of mecA, the gene coding for the low-affinity penicillin
      binding protein PBP2', in methicillin-resistant staphylococci. In the present
      report, we show that the regulation of methicillin resistance occurs primarily at
      the level of mecA transcription and that in the presence of intact plasmid pI524
      or mecR, the gene undergoes negative control. The relative amount of mecA mRNA
      present during exponential growth in uninduced cultures matches the type of mecA
      regulation and decreases in the following order: constitutive greater than pI524
      greater than mecR-dependent mecA expression. Induction of mecA by methicillin is
      faster in pI524- than in mecR-controlled strains. The overall mRNA half-life is
      similar for all strains analyzed. Our results indicate that methicillin
      resistance under mecR control in certain staphylococcal strains could escape
      detection by the standard disk diffusion test and broth microdilution test
      because of the very slow derepression of the mecA gene. This finding is of
      importance for the clinical detection of this type of methicillin resistance.

PMID- 1375450
TI  - Molecular cloning, functional expression and tissue distribution of the cDNA
      encoding frog skeletal muscle calsequestrin.
AB  - We have cloned, sequenced and expressed the cDNA encoding frog skeletal muscle
      calsequestrin. The processed frog calsequestrin is 398 residues long, with an Mr
      of 45941 (unglycosylated form), and exhibits 77% sequence similarity with its
      rabbit counterpart. Consensus sequences for glycosylation and phosphorylation of
      the protein were conserved. Compared with rabbit calsequestrin, the mature
      amphibian protein has peculiar structural properties, which include (i) a higher
      content of negatively charged residues (142 versus 109), and (ii) a striking
      repeat sequence at the C-terminal region of 44 aspartic acid residues.
      Furthermore, this is the first report on the expression of calsequestrin cDNA in
      COS-1 cells; the expressed protein exhibited an Mr and antigenic properties which
      were indistinguishable from those of the native protein. In addition, it was
      capable of binding 45Ca in a ligand overlay. Northern blot analysis of frog
      skeletal muscle, liver, heart and brain RNA showed that the protein is mainly
      expressed in skeletal muscle. The high density of negative charges at the C
      terminus might constitute high-capacity low-affinity Ca(2+)-binding sites, which
      may account for the higher Ca(2+)-binding capacity of frog calsequestrin compared
      with other members of the calsequestrin family (56 mol/mol versus 40-44 mol/mol
      of protein).

PMID- 1375451
TI  - Effects of guanidinium hydrochloride on the structure and immunological
      properties of Bordetella pertussis fimbriae.
AB  - Denaturation of Bordetella pertussis fimbrial preparations by guanidinium
      hydrochloride (GdnHCl) has been characterized using static light scattering,
      c.d., fluorescence and antibody recognition. The susceptibility of Fim2 + 3 (a
      mixed preparation of two fimbrial types) to GdnHCl was found to be highly
      dependent on pH; as the pH was increased from pH 7.2 to 10.5, the concentration
      of GdnHCl required to induce 50% denaturation was decreased. At pH 10.5, Fim2 + 3
      was denatured by GdnHCl in a three-step pathway comprising: (1) formation of a
      pre-denaturational intermediate at less than 1.0 M-GdnHCl; (2) dissociation of
      the fimbrial polymer into subunits between 2 M- and 3.2 M-GdnHCl; and (3) subunit
      unfolding between 2.8 M- and 3.6 M-GdnHCl. A similar pathway was also found for
      the denaturation of the individual fimbrial types, Fim2 and Fim3, except that
      unfolding of either subunit commenced at a lower GdnHCl concentration (2.2 M)
      than that found for the mixture of fimbriae, Fim2 + 3. The second step in the
      denaturation pathway, dissociation into subunits, was partially reversible, but
      the renaturation and reassociation of fully unfolded subunits to form fimbriae
      like structures was not achieved. These findings demonstrate that the GdnHCl
      denaturation of complex polymeric proteins is unlikely to follow a reversible two
      state denaturation pathway, and support the involvement of a chaperone-like
      protein in the folding and assembly of the fimbriae in vivo. Measurement of the
      ability of anti-fimbrial monoclonal antibodies to recognize intermediates in the
      denaturation pathway enabled the identification of two types of epitope which
      were dependent on different aspects of fimbrial tertiary/quaternary structure.

PMID- 1375452
TI  - Cyclic AMP does not inhibit collagen-induced platelet signal transduction.
AB  - The adhesion of platelets to collagen and their activation is the primary event
      in haemostasis. Following adhesion, platelet aggregation mediated by ADP,
      thromboxane A2 and thrombin leads to the formation of a platelet plug. It is
      known that platelet activation by each of these agonists involves an increase in
      the cytosolic free Ca2+ concentration, and this has been thought to be controlled
      by cyclic AMP. However, we report here that while signal transduction induced by
      ADP plus a thromboxane mimetic (U46619), or by thrombin, is inhibited by
      stimulators of adenylate cyclase such as a prostaglandin I2 (PGI2) analogue
      (Iloprost), PGD2 and forskolin, elevation of cyclic AMP does not inhibit either
      platelet adhesion to collagen or the associated Ca2+ mobilization, phosphatidic
      acid formation or 5-hydroxytryptamine secretion. Furthermore, collagen did not
      lower elevated levels of cyclic AMP in platelets measured in the presence of both
      a thromboxane antagonist and an ADP-removing system. The present results are
      discussed in the context of previous findings.

PMID- 1375454
TI  - Receptor-mediated regulation of IsK, a very slowly activating, voltage-dependent
      K+ channel in Xenopus oocytes.
AB  - Expression of IsK in Xenopus oocytes has been obtained in 2 ways: (i) by
      injection of cardiac polyA+ RNA from neonatal mouse heart; (ii) by injection of a
      cRNA synthesized in vitro. It was observed that polyA+ RNA not only directs the
      expression of the IsK channel but also contains purinergic P2 and endothelin
      receptors. Stimulation of these receptors, that produce intracellular Ca2+
      increase together with diacylglycerol production activating protein kinase C,
      increases IsK activity. The same type of results and the same conclusions were
      obtained by co-injecting cRNA's corresponding to the 5-HT2 receptor and the IsK
      channel into oocytes. This stimulatory effect was shown to be due to Ca2+ via a
      calmodulin-dependent kinase process. Conversely, activation of protein kinase C
      pathway alone by phorbol esters leads to inhibition of IsK activity.

PMID- 1375453
TI  - Amylase release from streptolysin O-permeabilized pancreatic acinar cells.
      Effects of Ca2+, guanosine 5'-[gamma-thio]triphosphate, cyclic AMP, tetanus toxin
      and botulinum A toxin.
AB  - The molecular requirements for amylase release and the intracellular effects of
      botulinum A toxin and tetanus toxin on amylase release were investigated using
      rat pancreatic acinar cells permeabilized with streptolysin O. Micromolar
      concentrations of free Ca2+ evoked amylase release from these cells. Maximal
      release was observed in the presence of 30 microM free Ca2+. Ca(2+)-stimulated,
      but not basal, amylase release was enhanced by guanosine 5'-[gamma
      thio]triphosphate (GTP[S]) (3-4 fold) or cyclic AMP (1.5-2 fold). Neither the two
      chain forms of botulinum A toxin and tetanus toxin, under reducing conditions,
      nor the light chains of tetanus toxin, inhibited amylase release triggered by
      Ca2+, or combinations of Ca2+ + GTP[S] or Ca2+ + cAMP. The lack of inhibition was
      not due to inactivation of botulinum A toxin or tetanus toxin by pancreatic
      acinar cell proteolytic enzymes, as toxins previously incubated with
      permeabilized pancreatic acinar cells inhibited Ca(2+)-stimulated
      [3H]noradrenaline release from streptolysin O-permeabilized adrenal chromaffin
      cells. These data imply that clostridial neurotoxins inhibit a Ca(2+)-dependent
      mechanism which promotes exocytosis in neural and endocrine cells, but not in
      exocrine cells.

PMID- 1375455
TI  - Endocytosis is regulated by protein kinase A, but not protein kinase C in a
      secretory epithelial cell line.
AB  - Endocytosis in the chloride secreting epithelial cell line T84 was monitored by
      uptake of the fluid-phase markers FITC-dextran and horseradish peroxidase (HRP).
      Uptake of marker was inhibited by incubation of cells at 4 degrees C, consistent
      with an endocytic uptake. Although activation of the cAMP-dependent second
      messenger pathway has been shown to stimulate exocytosis in this cell line, it
      caused a 63% reduction in endocytosis as measured by uptake of fluid-phase
      markers. In contrast, the presence of the protein kinase C activator phorbol
      myristate acetate (PMA) caused no significant reduction in the level of
      endocytosis compared to control, nor did it reverse the inhibitory effect of PKA
      activation. The data thus suggest that endocytosis in T84 cells is regulated
      through activation of protein kinase A, but not through activation of protein
      kinase C.

PMID- 1375456
TI  - Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot
      analysis.
AB  - A cDNA clone for the mouse thromboxane A2 receptor was isolated from mouse lung
      cDNA library. The cDNA has a 1,023 base pair open reading frame which encodes a
      protein of 341 amino acid residues. STA2 and U-46619 induced inward current in
      Xenopus laevis oocytes injected with the transcript of the clone. Specific
      binding of [3H]S-145 was found in membranes of COS-1 cells transfected with the
      cDNA (Kd = 3.3 nM) and was displaced with unlabeled prostaglandins and
      thromboxane analogues in the order of S-145 greater than STA2 greater than U
      46619 greater than PGD2 greater than PGF2 alpha = PGE2. Northern blot analysis
      demonstrated that thromboxane A2 receptor mRNA is expressed abundantly in thymus,
      spleen and lung.

PMID- 1375457
TI  - cDNA cloning of a neural visinin-like Ca(2+)-binding protein.
AB  - A 21,000-dalton Ca(2+)-binding protein (Walsh, M.P., Valentine, K.A., Ngai, P.K.,
      Carruthers, C.A., and Hollengerg, M.D. (1984) Biochem. J. 224, 117-127) was
      purified from the rat brain and through the use of oligonucleotide probe based on
      partial amino acid sequence, cDNA clones were obtained from rat brain cDNA
      library. The complete amino acid sequence deduced from the cDNA contains 191
      residues and has a calculated molecular mass of 22,142 daltons. There are three
      potential Ca(2+)-binding sites like the EF hands in the sequence. It displays
      striking sequence homology with visinin and recoverin, retina-specific Ca(2+)
      binding proteins. Northern blot analysis revealed that the protein is highly and
      specifically expressed in the brain.

PMID- 1375458
TI  - A 30 kDa functional size for the erythrocyte water channel determined in situ by
      radiation inactivation.
AB  - The functional unit size of the water channel in rabbit erythrocytes was assessed
      using target size analysis following radiation inactivation. Using Radiochromic
      nylon dosimetry, accurate values of accumulated dose yielded an absolute target
      analysis, leading to direct determination of molecular size. The erythrocyte
      water channel functional size was shown to be 30 kDa, and is identical to the
      size found in rat renal proximal tubule brush border membranes (1), suggesting
      close homology of these two water channels. The result suggests that the 28 kDa
      channel-like intrinsic protein (CHIP28) recently isolated from human erythrocytes
      and proximal tubule (2), which is believed to form water channels of oligomeric
      construction may have a functional water channel activity in monomeric form.

PMID- 1375459
TI  - Effect of NADPH oxidase inhibition on endothelial cell ELAM-1 mRNA expression.
AB  - Neutrophil adherence to endothelium is partially mediated by the expression of
      endothelial leukocyte adhesion molecule-1 (ELAM-1) on endothelial cells activated
      by agents such as lipopolysaccharide (LPS) and phorbol myristate acetate (PMA).
      To elucidate molecular mechanisms involved in the induction of ELAM-1 on
      endothelial cells, we investigated the effect of the NADPH oxidase inhibitor,
      apocynin (4-hydroxy-3-methoxyacetophenone), on ELAM-1 mRNA expression in human
      umbilical vein endothelial cells (HUVEC) by Northern blot analysis. Apocynin
      downregulated both LPS- and PMA-induced ELAM-1 mRNA expression in a dose
      dependent manner. Our results suggest NADPH oxidase might play a key role in ELAM
      1 mRNA expression in HUVEC.

PMID- 1375460
TI  - Induction of nitric oxide synthase is a necessary precondition for expression of
      tumor necrosis factor-independent tumoricidal activity by activated macrophages.
AB  - Various bacteria and bacterial products induce in pure, lymphocyte-free bone
      marrow-derived mononuclear phagocytes (BMMo) the generation of tumor necrosis
      factor, nitric oxide (NO) synthase, NO and nitrite (NO2-), the flow of L-arginine
      to citrulline, and tumoricidal activity. The flow of L-arginine to citrulline and
      formation of NO/NO2- on the one hand and expression of tumoricidal activity were
      not always closely related; however, these parameters were suppressed in a dose
      dependent manner by the flavoprotein inhibitor, diphenyleneiodonium (DPI) and the
      L-arginine analogue, NG-monomethyl-L-arginine (NMMA). The findings support the
      concept of a central role of the NO synthase pathway in the generation of tumor
      necrosis factor-independent tumoricidal activity by activated macrophages but the
      exact conditions which enable the transfer of the lytic principle from the
      effector to the target cell remain to be elucidated.

PMID- 1375461
TI  - A soluble form of prion protein in human cerebrospinal fluid: implications for
      prion-related encephalopathies.
AB  - The cellular prion protein (PrPc) is a 33-35 kDa sialoglycoprotein anchored to
      the external surface of neural and non-neural cells by a glycosyl
      phosphatidylinositol moiety. In addition, a secretory form of PrPc has been found
      in cell-free translation systems and in cell cultures. On this basis, we
      investigated human cerebrospinal fluid for the presence of soluble PrP and
      identified a protein whose molecular weight, antigenic determinants, N-terminal
      amino acid sequence and sensitivity to protease digestion corresponded to those
      of PrPc. In prion-related encephalopathies of humans and animals, the secretory
      form of PrPc might be converted into the abnormal isoform PrPSc and play a role
      in the dissemination of the disease process and amyloid formation.

PMID- 1375462
TI  - Endothelin receptors in human parathyroid gland.
AB  - We studied whether specific receptors for endothelins (ETs) exist in human
      parathyroid tissues and whether ETs may have any effect on secretion of PTH from
      parathyroid cells. Binding studies using [125I]ET-1 to the parathyroid membranes
      obtained from patients with hyperparathyroidism (2 adenomas, 2 hyperplasias)
      revealed that ET-1 competitively inhibited the binding of [125I]ET-1 to the
      membranes (the apparent Kd: 62 +/- 18 pM), whereas ET-3 showed biphasic and less
      steep inhibition curve than ET-1 in all tissue membranes examined. Northern blot
      analysis of poly(A)+ RNA from the parathyroid adenoma clearly demonstrated gene
      expression of both ETA and ETB receptors as well as preproET-1. ET-1 inhibited
      basal PTH secretion from dispersed adenoma cells more potently than ET-3. The
      present study clearly demonstrates the presence of both ETA and ETB receptor
      subtypes in human parathyroid tissues through which ETs may modulate PTH
      secretion in an autocrine and/or paracrine manner.

PMID- 1375463
TI  - Evolutionary conservation of the 14-3-3 protein.
AB  - The novel family of 14-3-3 proteins may be involved in the regulation of neuronal
      activity. During our search for proteins coordinately expressed with the
      prohormone proopiomelanocortin in the melanotrope cells of the Xenopus
      intermediate pituitary gland, we cloned and sequenced a pituitary cDNA encoding a
      Xenopus 14-3-3 protein. Alignment of the Xenopus protein with known mammalian,
      Drosophila and plant 14-3-3 polypeptide and with a mammalian protein kinase C
      inhibitor protein revealed that the neuron-specific 14-3-3-related proteins are
      highly conserved (60-88%) throughout eukaryotic evolution.

PMID- 1375465
TI  - Increased interleukin 1 receptor, type I, at messenger RNA and protein level in
      skin fibroblasts from patients with systemic sclerosis.
AB  - Summary. To elucidate the mechanisms of the fibrosis in systemic sclerosis (SSc)
      through the action of a cytokine, interleukin 1 (IL-1), we studied the specific
      biologic and biochemical features of interleukin 1 receptor (IL-1R) as expressed
      on the surfaces of fibroblast cells in cultures from 3 SSc patients and 3 normal
      donors. 125I-IL-1 beta binding assays revealed a high density of IL-1R on the
      cell surfaces of SSc fibroblasts as compared to those of normal subjects. We also
      found an enhanced expression of IL-1R messenger RNA (mRNA) in SSc fibroblasts,
      using Northern blot or slot blot analysis. These findings indicate that the
      expression of IL-1R on SSc fibroblasts were spontaneously induced at the
      transcriptional level. It is suggested that SSc fibroblasts are more sensitive to
      IL-1, and that the signal transduction of IL-1 through IL-1R may be eventually
      involved in the fibrosis of SSc.

PMID- 1375464
TI  - Structure of human prostatic acid phosphatase gene.
AB  - Two cDNA clones containing the complete protein-coding sequence of 1,188
      nucleotides as well as the 5' and 3' non-coding regions of human prostatic acid
      phosphatase (PAP) were isolated and sequenced. The size of PAP mRNAs from benign
      prostate hyperplasia and cancerous prostate was estimated to be 3.2Kb, indicating
      that the 3' downstream polyadenylation signal was used. Several genomic clones
      containing parts of the human PAP gene were isolated and the nucleotide sequence
      of ten exons and their flanking regions was determined. The protein-coding
      sequence of the human PAP gene was interrupted by nine introns. The positions of
      all nine introns present in the human PAP gene were homologous to those of the
      first nine introns in the human lysosomal acid phosphatase (LAP) gene. However,
      the last (11th) exon of the LAP gene encoding the COOH-terminal domain, which
      includes a transmembrane segment, was found to be absent in human PAP gene.
      Southern blot analysis of ten mammalian genomic DNAs gave multiple EcoRI
      fragments. The data of human genomic DNAs were consistent with the total length
      of the PAP gene of at least 50 kilobases.

PMID- 1375466
TI  - Nucleotide sequence of cDNA for Acacia confusa trypsin inhibitor and implication
      of post-translation processing.
AB  - Synthetic oligonucleotides corresponding to all possible sequences of N-terminal
      and C-terminal region of Acacia confusa trypsin inhibitor were used to generate
      ACTI-related sequences using the polymerase chain reaction on the cDNAs encoding
      ACTI of the seeds of legume, A. confusa. The deduced amino acid sequence agreed
      with that determined by the peptide analysis except an extra amino acid residue,
      serine, was found at the junction of A and B chain, which was removed by post
      translation processing with specific protease(s). The substrate specificity of
      the protease(s) was found to cleave at the C-terminal sites of asparagine and
      serine, which was also shown to be the same case for another plant protein,
      abrin, isolated from legume, Abrus precatorius.

PMID- 1375467
TI  - [Platelet group polymorphism in Provence. Comparison with the frequencies of
      platelet-specific allo-antigens observed in other populations].
AB  - Systems HPA-1 (Pla); HPA-3 (Bak) HPA-5 (Br) are involved in neonatal alloimmune
      thrombocytopenia and post-transfusion purpura. The frequencies of platelet
      specific antigens in these three systems have been studied among one hundred one
      unrelated blood donors from Provence (South of France) for three generations.
      Typing was performed by the MAIPA test (monoclonal antibody-specific
      immobilization platelet antigen). The phenotypes frequencies found were: HPA-1a
      (PlA1): 97%; HPA-3a (Baka): 88.1%. These frequencies are quite similar to those
      reported in Europe and North America, but are different compared to Oriental and
      South American populations. Our Provence population has the highest frequency of
      HPA-5b (Bra) yet reported: 23.8%. These results define the polymorphism of
      platelet-specific antigens in the Provence population. Similar studies, among
      other populations, would provide new data for geographical haematology, which has
      so far been based on erythrocyte, leucocyte and serum polymorphisms. The
      variations between populations in these platelet-specific polymorphisms would be
      so many useful descriptive elements for the epidemiological study of associated
      diseases.

PMID- 1375468
TI  - RNA metabolism, DNA damage and cellular resistance to X-rays: investigations in
      chick embryo and rat cells.
AB  - Three hours after X-irradiation in vivo with 8 Gy the in vitro incorporation of
      [3H]uridine into total RNA of liver(L)- and brain(B)-cells of the chick embryo
      was reduced to 77% and 90%, respectively; the mRNA fraction was strongest
      inhibited. Under the same conditions, protein synthesis of L-cells declined to
      62%, while protein synthesis of B-cells was not influenced. RNA and protein
      metabolism was not altered following X-irradiation in vitro (1.75-56 Gy).
      Compared to thymic- and splenic cells of the rat, chicken embryo cells exhibited
      higher constitutive poly(adenosine diphosphate-ribose)polymerase activity and
      lower X-irradiation-induced DNA damage. Whereas the slight inhibition of RNA and
      protein synthesis by X-irradiation in ovo may be an abscopal and/or secondary
      phenomenon reflecting DNA and/or cellular damage, the present investigations
      comprising various cell types argue for an efficient DNA repair in chicken embryo
      cells caused, at least partly, by a high constitutive activity of DNA repair
      proteins.

PMID- 1375469
TI  - The blood group antigens (BGA)-related glycoepitopes. A key structural
      determinant in immunogenesis and cancer pathogenesis.
AB  - This overview has been focused on the functional and pathophysiological aspects
      of blood group antigens (BGA)-related glycodeterminants. It has been postulated
      that in a broad range of histogenetically different tissues and organs BGA
      related glycoepitopes are expressed on the cell surface at definite stages of
      cell differentiation during embryogenesis, organogenesis, tissue repair,
      regeneration, remodeling and maturation when 'sorting-out' behaviour of one
      homotypic cell population from heterotypic assemblage of cells occurs. In this
      event the BGA-related glycoepitopes, if being expressed on the cell surface, play
      a role of key structural determinants in cell-cell recognition, association and
      aggregation. This mechanisms has been discussed in relation to immunogenesis
      regarding of antigen presentation, self-non-self discrimination, positive and
      negative selection during thymic education. It is postulated that the appearance
      of the BGA-related glycoepitopes on the cell membrane is a consequence of the
      association of MHC and peptides, with subsequent elimination of cells carring
      high density of BGA-related glycoepitopes on their surface. In cancer it has been
      considered as a key mechanism of phenotypic divergence of tumor cells,
      immunoselection, tumor progression and metastasis.

PMID- 1375470
TI  - Molecular screening of partners of cystic fibrosis heterozygotes.
AB  - We have screened 100 partners of known or suspected CF heterozygotes for ten CF
      mutations which account for 88% of the CF mutations seen by us on CF chromosomes.
      We have identified six CF heterozygotes amongst the 100 low-risk people screened.
      As two of the six people at high-risk of being CF carriers were subsequently
      shown not to be CF carriers this gave rise to four couples with a one in four
      risk of CF in a pregnancy and so far to two PND's. The risk of CF in the
      remaining 94 couples was reduced to less than one in 800. We have concentrated on
      the screening of partners for the commoner CF mutations rather than haplotyping
      them for the CF linked markers XV-2c/TaqI and KM19/PstI which are in linkage
      disequilibrium with CF. For individuals shown not to carry these ten mutations, a
      five fold difference in risk of being a CF carrier remains between those who have
      the XV-2c/KM19 genotypes associated with the highest risk(BB), as compared to
      those with the lowest risk(CC). Nevertheless we feel that effort is better
      expended in mutation screening rather than haplotyping.

PMID- 1375471
TI  - Specialization, tolerance, memory, competition, latency, and strife among T
      cells.
AB  - Over the last four decades much insight has been gained into the working of T
      cells. This survey offers an interpretation of regulatory T-cell function in
      terms of epitope linkage and the need to free B cells of responsibility for self
      tolerance. These functions dictate specialized forms of antigen presentation, by
      separate populations of dendritic cells. Tolerance induction among T cells occurs
      at a threshold of antigen concentration which is close to that required for
      positive stimulation, as would be expected for the efficient working of the
      immune system. Certain self-proteins, especially those located on cell surfaces,
      also induce tolerance among B cells, thus reducing the danger of activating
      latent epitopes. Memory among T cells is attributed to two components, one of
      hyperreactivity of activated cells, and the other of clonal expansion. Examples
      of competition and buffering between T-cell activities are given. A brief
      discussion of autoimmune disease focusses on the importance of disease remission,
      protective HLA genes, and immunoinhibitory genes in animal models. The mechanism
      underlying all three may be a balance between competing subsets of T cells.

PMID- 1375472
TI  - Immunological aspects of demyelinating diseases.
AB  - Primary demyelination in the central nervous system results from damage to the
      myelin sheath or oligodendroglia and can be produced by a variety of mechanisms,
      including metabolic disturbances, toxicities, infection, and autoimmunity. The
      major human demyelinating disease affecting the central nervous system is
      multiple sclerosis (MS). Although the etiology of MS is not known, existing data
      indicate that both genetic and environmental factors contribute to pathogenesis.
      Experimental allergic encephalomyelitis (EAE) is induced by immunization of
      genetically susceptible animals with myelin proteins. This is mediated by
      autoimmune T cells. Characterization of MHC restriction, fine specificity of
      antigen recognition, and T cell receptor (TCR) usage by encephalitogenic T cells
      has resulted in highly specific immunotherapies. Both HLA and TCR genes have been
      linked to susceptibility for MS which is widely believed to be mediated by T
      cells that recognize an as yet unidentified autoantigen. Because of the advances
      in the understanding and treatment of EAE, recent research in MS has been focused
      on the characterization of cellular immune responses against myelin components.
      The results of these studies are reviewed and the potential implications of these
      findings for the pathogenesis and future therapy of MS are examined.

PMID- 1375473
TI  - Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal
      transduction.
AB  - CsA, FK-506, and rapamycin are microbial products with potent immunosuppressive
      properties that result primarily from a selective inhibition of T lymphocyte
      activation. Although chemically unrelated, CsA and FK-506 affect a similar subset
      of calcium-associated signaling events involved in the regulation of lymphokine
      gene expression, activation-driven T-cell death and exocytosis. Rapamycin has
      structural similarity with FK-506 but suppresses T-cell activation at a different
      level, mainly through inhibition of proliferation induced by growth-promoting
      lymphokines. CsA interacts with an abundant 17 kDa protein, termed cyclophilin,
      that possesses peptidyl-prolyl cis-trans isomerase (PPIase) activity. Additional,
      minor cyclophilin-like molecules have been identified. Both FK-506 and rapamycin
      interact with FKBP, a 12 kDa protein, which, although unrelated to cyclophilin,
      is also abundant and ubiquitous, has a similar enzymatic activity, and is a
      member of a larger family of FKBPs. All three immunosuppressants inhibit the
      PPIase activity of their respective binding proteins. However,
      nonimmunosuppressive analogs of CsA and FK-506 are also inhibitory, indicating
      that inhibition of PPIase activity is not directly implicated in
      immunosuppression. Moreover, only a small fraction of the cellular pool of the
      major forms of cyclophilin or FKBP needs to be occupied by the drugs in order to
      achieve maximal immunosuppression. These observations suggest that complexes
      formed between the drugs and their major binding proteins may affect the function
      of other, unidentified, molecules or, alternatively, that minor binding proteins
      may play a role in the drugs' action. Further characterization of the biochemical
      processes altered by CsA, FK-506, and rapamycin should yield important insights
      into the signal transduction pathways involved in T-cell activation and should
      help in the development of novel immunosuppressive agents.

PMID- 1375474
TI  - Lymphocyte development from stem cells.
AB  - Highly enriched pluripotent and multipotent hematopoietic stem cells (HSCs) are
      isolated from bone marrow and fetal liver as Thy-1loLin-Sca-1+ cells. Pluripotent
      HSCs express c-kit receptor on their surface, but the generation and
      proliferation of early fetal HSCs take place in the absence of steel factor. T
      precursor cells migrate into the fetal thymus by chemotactic mechanism. CD4lo
      precursors represent a newly defined phase of T-cell development in the thymus
      between the bone marrow-derived stem cells and the CD4-8- intrathymic precursors.
      Only fetal, but not adult, HSCs have the capacity to differentiate into V gamma
      3+ and V gamma 4+ T cells under the fetal thymic microenvironment, and HSC
      themselves may lose some of their developmental potential during ontogeny. It is
      postulated that HSCs are the locus of a complicated but precise developmental
      clock that may determine both the time-dependent closure of some gene loci (e.g.
      V gamma 3 and V gamma 4 T cell receptor, and embryonic and fetal globin) and the
      activation of others (e.g. the N nucleotide insertion machinery).

PMID- 1375475
TI  - Production of cystic fibrosis transmembrane conductance regulator in the milk of
      transgenic mice.
AB  - Here we describe the production of cystic fibrosis transmembrane conductance
      regulator (CFTR), the product of the gene associated with cystic fibrosis, in the
      milk of transgenic mice. Mammary specific expression was achieved by placing the
      CFTR cDNA under the control of the goat beta-casein gene promoter. By
      fractionation, CFTR was shown to be associated with the membranes that envelop
      milk fat globules as they are discharged from the apical surface of the mammary
      epithelia. Since milk fat globules may comprise up to 10% of whole milk, this
      represents a novel, inexpensive and efficient approach to produce CFTR and
      possibly other membrane-associated proteins. The availability of large quantities
      of CFTR could have important implications for the development of new therapies
      for cystic fibrosis.

PMID- 1375476
TI  - Nucleotides and ion channel regulation.

PMID- 1375477
TI  - The effect of recombinant stem cell factor (SCF) on purified CD34-positive human
      umbilical cord blood progenitor cells.
AB  - We describe the effect of soluble c-kit ligand (stem cell factor, SCF) on highly
      purified CD34-positive hemopoietic progenitors from human umbilical cord blood.
      Progenitor cells were purified from cord blood mononuclear cells by immune
      rosetting with lineage specific antibodies and subsequent sorting of the rosette
      negative population for CD34(BI3C5)-positive cells. This procedure enriched
      greater than 100-fold for colony forming cells (CFC). Using optimal
      concentrations of colony-stimulating factors (CSF) without added SCF
      approximately 2.5% of cells formed colonies. SCF also had CSF activity on this
      population, up to 0.5% of cells forming small colonies in response to SCF alone.
      In contrast, the addition of SCF to optimal concentrations of the other growth
      factors produced a greater than 10-fold increase in colony number. However, the
      most notable effect was an approximately 100-fold increase in the number of cells
      in each colony. Equally striking was the very high proportion (50-80%) of mixed
      colonies (CFU-MIX). These findings suggest the progenitor cell pool in cord blood
      is skewed towards very early cells. However, when day 14 colonies formed in
      response to SCF and other factors were assessed for their re-cloning potential
      they did not contain significant numbers of CFC, implying that SCF did not
      support the self-renewal of these CD34 positive cord blood progenitor cells.
      These findings support a role for SCF as an enhancing factor for hemopoietic
      progenitor cells but it does not promote self-renewal in these populations.

PMID- 1375478
TI  - Purification from transformed mouse fibroblast of a cell growth inhibitor which
      is an IGF-binding protein.
AB  - From medium conditioned by 3T3 cells, we had previously purified an inhibitory
      factor of Mr 45 kDa which we termed IDF45 (inhibitory diffusible factor). The
      protein was able to 100% inhibit stimulation induced in CEF by 1% calf serum and
      to reversibly prevent cell growth. We then demonstrated that IDF45 was an IGF
      binding protein. Our results suggested that IDF45 was a bifunctional molecule
      able to bind IGF and to inhibit DNA synthesis stimulated by this hormone, but
      also to inhibit stimulation of DNA synthesis induced by another growth factor in
      serum. Indeed, its N terminal amino acid sequence has great homology with that of
      IGFBP-3 and IDF45 is now proposed to be named IGFBP-3 (mouse IGF binding
      protein). Present results show that Ha-ras transfected 3T3 cells (EJ cells), like
      3T3 cells, secrete a mIGFBP-3 molecule. In addition, transfected cells secrete a
      doublet of an IGF-binding protein (IGFBP-28) of Mr 28 kDa which is not secreted
      by untransformed 3T3 cells. IGFBP-28 has been purified and characterized in this
      work. Various results suggest that IGFBP-28 is not a degradation product of
      mIGFBP-3. Its N terminal amino acid sequence was different from that of mIGFBP-3.
      IGFBP-28 inhibited DNA synthesis stimulated by IGF-I, but much more IGFBP-28
      protein than mIGFBP-3 was required to prevent this stimulation. In agreement with
      this result, IGFBP-28 has low affinity for IGF-I. In contrast, IGFBP-28 has high
      affinity for IGF-II. Like mIGFBP-3, IGFBP-28 was able to inhibit the stimulation
      induced by serum in CEF and to reversibly prevent growth, though with a specific
      activity lower than that of mIGFBP-3. It has also the capacity to inhibit
      stimulation of DNA synthesis induced by high molecular weight serum proteins
      depleted in IGF-I and II. In conclusion we have shown that transformation of 3T3
      cells with Ha-ras induced the synthesis of a new IGF binding protein in medium
      conditioned by normal 3T3 cells. Our results suggest that IGFBP-28 like mIGFBP-3
      is a bifunctional protein able to inhibit stimulation induced by IGF and by serum
      proteins different from IGFs.

PMID- 1375480
TI  - [Non-verbal auditory agnosia with EEG abnormalities and epilepsy; an unusual case
      of Landau-Kleffner syndrome].
AB  - A case of unusual Landau-Kleffner syndrome was reported. She was an 8 year-old
      girl and showed non-verbal agnosia, diffuse EEG abnormalities and convulsions.
      Her responses to both verbal and non-verbal sounds remained inconsistent and
      unstable. When a continuous spike-wave complexes on EEG was detected, she paid no
      attention to any sound in spite of her fair consciousness. Auditory brainstem
      response and magnetic resonance imaging of her brain were normal. Auditory
      agnosia was correlated well with EEG abnormalities, and valproic acid and
      clonazepam were effective for EEG improvement. After the EEG improvement,
      clinical responses to sounds recovered well; firstly she could pay attention to
      sounds and then she could distinguish between verbal and non-verbal sounds.
      Finally, she could speak a few words after the learning letters.

PMID- 1375479
TI  - Inhibition by methylprednisolone acetate suggests an indirect mechanism for TGF-B
      induced angiogenesis.
AB  - Angiogenesis induced by transforming growth factor beta (TGFB) implanted in the
      rabbit cornea is accompanied by an influx of inflammatory cells. To determine if
      the inflammatory cells are the mediators of the neovascularization, they were
      depleted by local administration of methylprednisolone acetate (MPA).
      Subconjunctival injections of 16 mg of MPA immediately following implantation of
      50 ng of TGFB in the cornea prevented the inflammation and subsequent formation
      of capillaries. If the injections of MPA were delayed by 48 hr and the
      inflammatory cells were allowed to enter the cornea, angiogenesis occurred,
      demonstrating that MPA had no adverse effects on the ability of endothelial cells
      to form capillaries. These results confirm the hypothesis that TGFB induces
      angiogenesis indirectly by recruiting inflammatory cells capable of stimulating
      direct angiogenesis.

PMID- 1375481
TI  - Definition of immunogenic determinants of the human papillomavirus type 16
      nucleoprotein E7.
AB  - Specific T lymphocyte lines and T cell clones were established from peripheral
      blood mononuclear cells of asymptomatic seropositive individuals employing
      synthetic peptides which correspond to the sequence of the human papillomavirus
      (HPV) type 16 transforming protein E7. Specificity analysis of T cells as
      determined by means of [3H] thymidine incorporation after stimulation with
      individual peptides revealed three immunogenic determinants of E7 that are
      recognised in association with at least two different HLA haplotypes. One N
      terminal region (aminoacids 5-18) was recognised by one T cell line. T cell
      clones and the corresponding T cell line established from another donor responded
      to a different N-terminal (17-38) and to a C-terminal region (69-86). The N
      terminal sequence 5-18 and the C-terminal determinant contain a periodicity of
      hydrophilic and hydrophobic residues that have been found in many T cell
      epitopes. Phenotypic characterisation of T cell clones by indirect
      immunofluorescence revealed that the T cell clones expressed the CD4 surface
      glycoprotein suggesting that the specific E7 determinants were recognised in
      association with major histocompatibility complex (MHC) class II molecules. With
      regard to functional properties, at least three T cell clones exhibited specific
      cytotoxic activity towards autologous B lymphocytes transformed by Epstein-Barr
      virus in the presence of the relevant HPV16 E7 peptides. The implications of
      these results regarding the development of vaccination strategies and host-virus
      interaction are discussed.

PMID- 1375482
TI  - Aneuploid subpopulations in tumour-invaded lymph nodes from breast cancer
      patients.
AB  - Fresh, paired primary tumours and lymph node metastases from breast cancer
      patients were compared by DNA flow cytometry. Although 65% of primary tumours
      were aneuploid, the detection of aneuploid peaks in corresponding nodal
      metastases was rare (only 6 cases out of 25) in single-parameter DNA analysis.
      Detection of aneuploid subpopulations in lymph nodes was greatly improved in dual
      parameter DNA analysis using an anticytokeratin (CK) antibody which allowed
      ploidy determination on CK+ epithelial cells alone. Examination of 12 lymph nodes
      for CK+ cells revealed the presence of both diploid and aneuploid tumour cells in
      tumour invaded nodes. In patients with multiploid primary tumours, a
      subpopulation of the primary aneuploid cells was dominant in the nodal
      metastases. This suggests that aneuploidy is an integral property of metastatic
      cells and that within a primary tumour a subpopulation may have a higher
      metastatic potential.

PMID- 1375483
TI  - Cytotoxicity of 5-aza-2'-deoxycytidine in a mammalian cell system.
AB  - After the addition of 5-aza-2'-deoxycytidine, a potent inhibitor of DNA
      methylation and S-phase-specific cytotoxic agent, metaphase chromosomes of
      Chinese hamster ovary (CHO) cells exhibited a highly decondensed and extended
      morphology (numerous "fragile sites") at the first mitotic division. However,
      when a lethal dose of this drug was added in early G1 phase to cells synchronised
      by mitotic selection, the majority subsequently divided at the same time as an
      untreated control cell population with few division abnormalities and with few of
      the more usual types of chromosome aberrations such as gaps, breaks and
      exchanges. The drug-treated cells also entered and completed the second S-phase
      without significant delay and it was only at the second mitosis after addition of
      5-azadeoxycytidine that cells showed delays in entering mitosis and significant
      increases in abnormal divisions concomitant with a modest increase in chromosome
      aberrations. If cells in a tumour behave similarly, the tumour mass would be
      expected to double before any reduction in tumour burden could be expected to
      occur.

PMID- 1375484
TI  - Expression of pp60c-src in human small cell and non-small cell lung carcinomas.
AB  - c-src protein was found in 60% of lung carcinomas (20 of 33 cases or primary
      tumours) by immunoblotting with a monoclonal antibody (Mab 327) and
      immunohistochemistry with serum from rabbits bearing tumours induced by Rous
      sarcoma virus. src protein expression was assessed in 4 small cell lung
      carcinomas and in an atypical carcinoid of neuroendocrine origin. However, pp60c
      src was also found in non-small cell lung carcinomas: in 60-80% of
      adenocarcinomas and bronchiolo-alveolar cancers and in 50% of squamous cell
      carcinomas. In the squamous cell carcinomas, src protein was expressed more
      frequently in poorly differentiated than in well and moderately differentiated
      carcinomas. Expression of pp60c-src was not found in epithelial cells of
      histologically unchanged lung tissues. These results show that pp60c-src may be
      activated in human lung carcinomas of different histopathological types.

PMID- 1375485
TI  - The capacity of peripheral blood stem cells mobilised with chemotherapy plus G
      CSF to repopulate irradiated marrow stroma in vitro is similar to that of bone
      marrow.
AB  - After treatment of patients with intermediate or high grade non-Hodgkin lymphoma
      with chemotherapy plus G-CSF the numbers of haemopoietic progenitor cells in the
      circulation increased to a mean of 226-fold for mixed CFC (Mix-CFC), 278-fold for
      GM-CFC and 29-fold for erythroid burst forming unit (BFU-E). The mean increase
      was modest (7-12-fold) for patients treated with chemotherapy alone. Peripheral
      blood mononuclear cells harvested at the time of the peak in the numbers of
      progenitors, or 2-4 days before the peak, seeded onto irradiated marrow stroma in
      vitro, repopulated the stroma and generated active haemopoiesis at least as
      effectively as bone marrow cells on a cell per cell basis. This is in contrast to
      the poor repopulating capacity of pretreatment blood. The results indicate that
      not only the progenitor cells, but also the repopulating stem cells migrated into
      the blood after chemotherapy plus G-CSF in sufficient numbers to allow harvesting
      and successful grafting without the possible complication of late haemopoietic
      failure.

PMID- 1375486
TI  - Serum lactate dehydrogenase isoenzyme 1 and tumour volume are indicators of
      response to treatment and predictors of prognosis in metastatic testicular germ
      cell tumours.
AB  - 44 patients with metastatic testicular germ cell tumours treated with cisplatin
      based chemotherapy were evaluated for prognostic implications of clinical
      characteristics. 22 obtained complete remission by the initial chemotherapy, and
      30 are disease-free. S-LDH-1 had an overall predictive value regarding the
      response of 80%, S-LDH of 64%, S-AFP of 62%, and S-hCG of 62%. In multivariate
      analysis regarding response, only tumour volume classified according to the Royal
      Marsden system (P = 0.0036) and S-LDH-1 (P = 0.0069) yielded information.
      Regarding survival, S-LDH-1 (P = 0.0141) and an estimate of total tumour mass (P
      = 0.0171) had most impact with additional information from S-hCG only (P =
      0.0536). We conclude that S-LDH-1 may be used as a tumour marker in addition to S
      hCG and S-AFP in patients with metastatic testicular germ cell tumour.

PMID- 1375487
TI  - Treatment of metastatic testicular tumours with bleomycin, etoposide, cisplatin
      and vincristine.

PMID- 1375488
TI  - The use of palliative radiotherapy in the management of breast cancer.

PMID- 1375489
TI  - [Tendinitis of the palmaris longus muscle. Apropos of 24 cases].
AB  - Twenty-four cases of flexor carpi radialis tendinitis were diagnosed between 1985
      and 1989 by SOS Main Strasbourg. This condition typically occurs in women (75%)
      with a mean age of 47 years with no particular occupational activity who present
      with spontaneous and induced pain along the distal part of the tendon.
      Examination may reveal disturbances of cutaneous sensation in the territory of
      the palmar cutaneous branch of the median nerve and associated signs: cysts
      (10/24 cases), scapho-trapezium osteoarthrosis (3 documented cases). Medical
      treatment provided good results in 7 out of 9 patients reviewed after a mean
      follow-up of 15 months. In the event of failure, surgical treatment with opening
      of the compartment, provided 4 good results in 6 patients reviewed after a mean
      follow-up of 2 years 4 months.

PMID- 1375490
TI  - [The value of pollicization in the reconstruction of thumb injuries in adults.
      Observations apropos of 15 cases].
AB  - Pollicisation remains a good solution to restore the function of the adult thumb
      after injury. This technique requires a good knowledge of plastic hand surgery to
      perform an emergency or secondary reconstruction, sparing the functional
      integrity and enhancing the value of the stumps. The authors report their own
      experience of 15 cases treated between 1985-1990.

PMID- 1375491
TI  - [The Sauve-Kapandji operation. Analysis and results of 69 cases].
AB  - The authors present the results of 69 cases operated between 1983 and 1989. The
      indications were dominated by two aetiologies: degenerative lesions of the
      inferior radio-ulnar joint in rheumatoid arthritis: 58% of cases, and traumatic
      sequelae, predominantly secondary to fractures of the distal radius: 34% of
      cases. The authors stress the effects of distant lesions: skeletal lesions of the
      two bones of the forearm or the superior radio-ulnar joint. A third group of
      rarer indications consisted of painful dislocations of the inferior radio-ulnar
      joint in Madelung's disease (indication only applied to adults). There were two
      types of complications: complications due to excessively long or intra-articular
      screws, which were treated by removal of the screws and, more severe,
      ossifications of the zone of diaphyseal resection (5 cases) which interfered with
      the functional result in terms of mobility. Three cases required extensive
      diaphyseal resection. The results are analysed for each aetiological group in
      terms of pain, mobility prehensile strength after more than one year of follow
      up. Good results were obtained in 80% of cases of post-traumatic lesions (16
      cases). The insufficient results were related to associated lesions of the elbow
      or the 2 bones of the forearm. A good result was obtained in 3 out of 4 cases of
      Madelung's disease and one case, operated elsewhere and revised by
      pseudoarthrodesis, obtained a moderate result. Lastly, in rheumatoid arthritis,
      the results in terms of pain, mobility and prehensile strength were good, apart
      from 2 failures due to progression of rheumatoid disease (cases unsuitable for
      this treatment). Radiographic analysis according to Youm and Mac Murtry's
      criteria showed minimal regression in the carpoulnar translation index (pre-op:
      0.28; post-op: 0.22). Overall, the Sauve-Kapandji operation provided good quality
      clinical results when the indications and technique were rigorously applied.

PMID- 1375492
TI  - [Description of a vascularized bone graft taken from the head of the 2nd
      metacarpal bone].
AB  - The authors describe a new vascularised bone graft from the distal part of the
      second metacarpal. They report an anatomic study on 20 cadavers which
      demonstrates the existence of two dorsal first web arteries (superficial and
      deep). The existence of free anastomosis between the two arteries is
      demonstrated. The vascularisation of the bone graft relies upon the deep first
      web artery which lies against the lateral aspect of the bone. The operative
      procedure is described and the authors stress the necessity to transfer the
      vascularized bone graft with a large soft tissue pedicle.

PMID- 1375493
TI  - [The carpal bump].
AB  - Fiolle reported the first description of a "carpal boss". The "hump" is
      cosmetically disturbing and sometimes painful. It has to be distinguished from a
      ganglion. A lateral X-Ray with 30 degrees of supination reveals a spur or a
      styloid bone (12.5%). In a series of 44 patients, treated over a period of 7
      years, 21 needed operation for pain or a complication of previous surgery. The
      technique described by Cuono and Watson was successfully used without recurrence
      of deformity but in 2 cases some pain remained during strenuous efforts.

PMID- 1375494
TI  - [Chronic ulnar nerve compression syndrome at the elbow. Apropos of 74 cases].
AB  - Seventy-four patients were operated at Bichat hospital for chronic ulnar nerve
      entrapment at the elbow between 1982 and 1988. For 62 of them, the etiology of
      the compression was idiopathic and these cases were treated by neurolysis only
      or, if the nerve was unstable, by neurolysis associated with medial
      epicondylectomy. For 12 of them, the etiology of the compression was post
      traumatic and these cases were treated by anterior subcutaneous transposition of
      the nerve using a fat sling. The average follow-up is 28 months and the results
      take into account the clinical preoperative grading according Mac Gowan's
      classification: grade I subjective symptoms combined with hypoesthesia in ulnar
      fingers grade II: weakness and wasting of the interossei combined with subjective
      symptoms, grade III: marked weakness and wasting of the interossei, adductor
      pollicis, and hypothenar muscles combined with anesthesia in ulnar fingers. The
      62 idiopathic compressions treated by neurolysis only or, if the nerve was
      unstable, by neurolysis associated with medial epicondylectomy showed 51 very
      good and good results. The 12 post-traumatic compressions treated by anterior
      subcutaneous transposition of the nerve using a fat sling showed 9 very good and
      good results. The authors stress the importance of their approach which takes
      account of the clinical preoperative grading and the etiology of the compression
      in order to apply correct surgical treatment.

PMID- 1375495
TI  - [Lipofibroma of the median nerve. Apropos of a case].
AB  - Lipofibroma is a rare, benign nerve tumour corresponding to diffuse fibroadipose
      infiltration of the nerve, dissociating the fasciculi without invading them. The
      authors report a case of lipofibroma of the median nerve in a 32 year old man
      presenting with a soft swelling of the palmar surface of the thumb. Treatment
      consisted of intraneurodissection of the tumour arising exclusively from the
      medial collateral nerve of the thumb. With a follow-up of two years, there has
      been no recurrence of the tumour, but the patient has persistent decreased
      sensation of the ulnar half of the thumb pulp. The features of the lipofibroma
      and the therapeutic options are discussed in the light of the data reported in
      the literature.

PMID- 1375496
TI  - [Metastatic tumors of the soft tissues of the hand. Apropos of a case. Review of
      the literature].
AB  - Soft tissue metastases of the hands are rare tumours, representing 0.1% of all
      metastases. The authors report a personal case and review the literature
      concerning another 21 cases. The primary tumour is generally a lung or breast
      cancer. These metastases appear to be more frequent in men than in women. Their
      rarity can be explained by the absence of routine investigation of such sites.
      The development of such metastases always indicates a poor prognosis.

PMID- 1375497
TI  - [Severe and inveterate internal scapho-trapezial ligament sprain. Apropos of an
      unusual case].
AB  - The authors report the first case in the literature of a chronic injury of the
      medial scaphotrapezial ligament. The main clinical feature was elective pain over
      the lateral margin of the carpal tunnel which was increased with effort. The pain
      was disabling and complete remission is obtained after surgical repair of the
      ligament.

PMID- 1375498
TI  - [Treatment of old inveterate buttonhole lesions of the extensors by arthroplastic
      resection with implants].

PMID- 1375499
TI  - [Our personal suture technic of the flexor tendons of the fingers with immediate
      mobilization].

PMID- 1375500
TI  - [Radio-carpal amputation and prosthesis].
AB  - Radio-carpal amputation was rejected for a long time because of the difficulties
      of fitting both myoelectrical and mechanical prostheses, only allowing a purely
      aesthetic prosthesis. As a result of miniaturization of control systems and the
      progress in computers, we believe that this now constitutes the best site for
      amputation whenever it is possible. Preservation of the antero-posterior bony
      contours of the radius allows the use of short sockets attached by a system of
      clips. In this way, flexion-extension of the elbow is left free and the movements
      of pronation and supination can be used. Liberation of the proximal joints
      facilitates integration of the prosthetic hand.

PMID- 1375502
TI  - [French Society of Hand Surgery. List of members].

PMID- 1375503
TI  - [Belgian Society of Hand Surgery (Belgian Hand Group). List of members 1991].

PMID- 1375501
TI  - [Sensory retraining of the hand using gnosis rings].
AB  - Sensory reeducation is very important. Many methods are used but it is difficult
      to assess their efficiency. Besides the routine methods we are using the gnostic
      rings which have on their periphery 5 symbols: a letter = A, a number = 3, a
      geometrical figure = a circle, a rough surface and a smooth convex surface. The
      symbols of the rings are in 3 different sizes (1.5 - 1 and 0.5 cm). The gnostic
      rings have 3 advantages: 1) they allow a precise evaluation in percentage. 2)
      they require an important brain effort, 3) they may be kept in the pocket and
      used several times during the day.

PMID- 1375504
TI  - [Swiss Society of Hand Surgery. List of members 1992].

PMID- 1375505
TI  - Quantitative and qualitative differences in IL-2 and IL-4 expression in primary
      and secondary T cell stimulation.
AB  - Lymphocytes were concanavalin A (Con A) primed and the signal was withdrawn 4-48
      h post-stimulation by alpha-methyl-D-mannopyranoside (alpha MM) treatment. Upon
      restimulation IL-2 and IL-4 RNA expression was found to be greatly enhanced. Re
      expression of lymphokine RNA was dependent on signals delivered by Con A, anti
      CD3 antibodies or phorbolester plus ionomycin, and could not be achieved by
      either IL-2, phorbolester or ionomycin alone. Increased IL-2 re-expression was
      only possible when alpha MM was added early after primary stimulation, while the
      ability for enhanced IL-4 RNA re-expression persisted. IL-2 and IL-4 RNA re
      expression was characterized by increases in steady state precursor RNA levels
      and thus, presumably, increased rates of transcription. However, the high
      accumulation of IL-2 RNA observed upon restimulation was also due to greatly
      increased RNA stability (greater than 4 h versus 30 min after primary
      stimulation). Thus, secondary expression of IL-4 RNA is persistent and mostly due
      to quantitative changes in transcription, whereas enhanced re-expression of IL-2
      RNA also results from altered post-transcriptional regulation. This phenotype,
      however, is only short lived.

PMID- 1375506
TI  - Different effects of pemphigus antibody and plasmin on the distribution of
      keratin intermediate filaments and desmoplakins between cultured oral and
      epidermal keratinocytes.
AB  - In order to clarify the molecular mechanism of blister formation in oral mucosa
      in pemphigus vulgaris (PV) comparing with that in epidermis, we analyzed the
      effects of PV serum on the distribution of keratin intermediate filaments (KIFs)
      and desmoplakins in oral as well as epidermal cultured keratinocytes by
      immunofluorescence microscopy using anti-keratin and anti-desmoplakin I/II
      monoclonal antibodies. After incubation with PV serum for 96 h at 37 degrees C,
      clusters of anti-keratin positive dots were formed around the nucleus in some of
      the keratinocytes from normal gingiva and soft palate but not in keratinocytes
      from tongue and skin, and desmoplakins also changed their distribution from
      linear arrangement at cell-cell contacts to clusters of dots around the nucleus
      in gingiva but not in epidermal keratinocytes. The dotted structures similar to
      those induced by pemphigus serum were formed also by incubation with human
      plasmin in gingival keratinocytes. However, no dot-formation of keratins was
      induced in these cells after incubation with trypsin. Furthermore, in epidermal
      keratinocytes, no keratin-dot formation was observed even after incubation with
      plasmin or trypsin. These results suggest that the dotted structures of KIFs
      caused by PV serum and plasmin might be a feature characteristic for the response
      of oral keratinocytes to PV serum and that there are some distinct differences in
      susceptibility to, and mode of, bulla formation between oral epithelium and
      epidermis.

PMID- 1375507
TI  - Prostacyclin analogues inhibit tissue factor expression in the human monocytic
      cell line THP-1 via a cyclic AMP-dependent mechanism.
AB  - Increased expression of tissue factor procoagulant by peripheral blood monocytes
      has been implicated in a number of thrombotic disorders. The present studies were
      undertaken to determine whether stable analogues of prostacyclin, a potent
      endothelium-derived platelet inhibitor and vasodilator, could inhibit tissue
      factor expression by human monocytic cells. Exposure of monocytic tumor THP-1
      cells to 100 ng/ml endotoxin, 2 units/ml interleukin-1 beta, or 5 ng/ml tumor
      necrosis factor-alpha for 4 hours led to increased tissue factor procoagulant
      activity. Preincubation for 30 minutes with iloprost, ciprostene, and carbacyclin
      led to a dose-dependent inhibition of tissue factor expression induced by all
      three challenging agents. Iloprost was the most potent: 50% inhibition occurred
      at 5 nM, a concentration close to the reported dissociation constant for iloprost
      binding to the platelet prostacyclin receptor. An orally active analogue,
      cicaprost, was equally effective against endotoxin-induced tissue factor
      expression. Carbacyclin and ciprostene were 100 times less potent. Iloprost
      prevented the endotoxin-induced expression of tissue factor antigen on the
      surface of THP-1 cells, as determined by flow cytometry. Iloprost (500 pM-50 nM)
      increased intracellular levels of cyclic AMP. This effect was potentiated by
      isobutylmethylxanthine, an inhibitor of phosphodiesterase. The inhibitory effects
      of iloprost on tissue factor expression were also potentiated by
      isobutylmethylxanthine and mimicked by forskolin and dibutyryl cyclic AMP but not
      dibutyryl cyclic GMP. These results suggest that prostacyclin may play a role in
      downregulating tissue factor expression in monocytes, at least in part via
      elevation of intracellular levels of cyclic AMP.

PMID- 1375508
TI  - Antifibrinolytic activities of alpha-N-acetyl-L-lysine methyl ester, epsilon
      aminocaproic acid, and tranexamic acid. Importance of kringle interactions and
      active site inhibition.
AB  - alpha-N-acetyl-L-lysine methyl ester (NALME) is a lysine analogue that reportedly
      binds to low-affinity lysine binding sites in plasmin(ogen) and
      miniplasmin(ogen). In the studies presented here, we show that NALME has
      antifibrinolytic activity; however, unlike the therapeutic agents epsilon-amino-n
      caproic acid (epsilon ACA) and tranexamic acid (TEA), the activity of NALME is
      based on inhibition of the plasmin active site. NALME (0.1-10 mM) significantly
      inhibited the amidase activity of plasmin, miniplasmin, and streptokinase-plasmin
      complex without affecting alpha-thrombin or tissue plasminogen activator. epsilon
      ACA and TEA (0.1-10 mM) did not affect the amidase activity of plasmin or
      miniplasmin. A kinetic analysis showed that NALME is a competitive inhibitor of D
      Val-L-Lys-p-nitroanilide HCl (S-2251) hydrolysis by plasmin; NALME binding to
      plasmin completely prevented S-2251 binding. The Kl for the plasmin-NALME
      interaction was 0.4 mM. epsilon ACA and TEA inhibited fibrin monomer digestion by
      plasmin and miniplasmin without binding to the active site of either enzyme. This
      result suggests that epsilon ACA and TEA function as antifibrinolytics by
      disrupting the noncovalent association of fibrin monomer with a domain common to
      both plasmin and miniplasmin (probably kringle 5). NALME inhibited fibrin monomer
      digestion principally by decreasing amidase activity. NALME was the only lysine
      analogue that prevented fragment X formation; TEA and epsilon ACA primarily
      inhibited the formation of fragments Y and D. When plasmin was incubated
      simultaneously with alpha 2-antiplasmin and alpha 2-macroglobulin, epsilon ACA
      increased the fraction of plasmin reacting with alpha 2-macroglobulin; NALME had
      no effect on the plasmin distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375510
TI  - Comparison of N-glycosides of fetuins from different species and human alpha 2-HS
      glycoprotein.
AB  - Complex type N-glycosides of commercial bovine fetuin preparations from pooled
      fetal calf serum have been shown to contain comparable amounts of Gal4,4,4TRI
      (see structure A below) and Gal4,4,3TRI (structure B) as major asialo-structures.
      To investigate whether there is a clear genetic specificity for synthesis of
      these oligosaccharides, N-glycosides from two preparations of bovine fetuin, each
      from a single calf, were examined. Both of these structures were present in each
      calf, and there was only a subtle quantitative difference in the ratio of these
      two structures between the calves. Thus, a specific galactosyltransferase,
      presumably required for the biosynthesis of the Gal4,4,3TRI structure, may exist
      in both of these individual calves. Comparison of fetuin N-glycosides was also
      extended to sheep, pig, and human alpha 2-HS-glycoprotein, the human counterpart
      of bovine fetuin, using high-pH anion-exchange chromatography of the reducing
      oligosaccharides as well as HPLC of their pyridinylamino derivatives. The N
      glycosides of ovine fetuin also have both Gal4,4,4TRI and Gal4,4,3TRI structures
      in a ratio similar to that of bovine fetuin. However, the major N-glycoside of
      porcine fetuin is of a fucosyl biantennary complex type structure (structure C
      below) and human alpha 2-HS-glycoprotein has an N-glycoside which is almost
      exclusively a nonfucosylated biantennary structure (structure D). This species
      specific presence of N-glycosides of fetuins and comparison with N-glycosides of
      other glycoproteins suggest that the polypeptide sequence of a glycoprotein may
      affect its N-glycan structure by regulating the activity of specific
      glycosyltransferases. [formula: see text]

PMID- 1375509
TI  - Pentraxin family of proteins interact specifically with phosphorylcholine and/or
      phosphorylethanolamine.
AB  - Pentraxins are a family of serum proteins characterized by five identical
      subunits that are noncovalently linked. The two major types of pentraxins are C
      reactive protein (CRP) and serum amyloid P component (SAP). CRP proteins are
      identified by their calcium-dependent interaction with phosphorylcholine. This
      study showed that SAP also bound to phosphorylated compounds but had a high
      specificity for phosphorylethanolamine. Thus, human CRP and SAP show high
      specificity that is complementary for the related compounds, phosphorylcholine
      and phosphorylethanolamine, respectively. This relationship suggests a
      complementary and/or related function for the pentraxins. Pentraxins from other
      species were also examined. Mouse SAP showed binding interactions and specificity
      similar to human SAP. Female protein (FP) from hamster and rat CRP showed a
      hybrid specificity and bound to both phosphorylethanolamine and
      phosphorylcholine. All of the proteins that bound phosphorylethanolamine also
      associated with human C4b-binding protein (C4BP). With the exception of human and
      rat CRP, all the proteins also bound to vesicles containing acidic phospholipids.
      All of these binding interactions were calcium-dependent and mutually exclusive,
      suggesting that they involved the same site on the protein. These findings
      suggest possible ways to examine the function of the pentraxins.

PMID- 1375512
TI  - The increased K+ leak of malaria-infected erythrocytes is not via a Ca(2+)
      activated K+ channel.
AB  - Charybdotoxin and nitrendipine both inhibited K+(86Rb+) influx via the Ca(2+)
      activated channel of uninfected erythrocytes but had no effect on K+(86Rb+)
      transport in malaria-infected cells. Activation of the channel in uninfected
      cells in which the cytoplasmic [Na+]/[K+] ratio was adjusted to be comparable
      with that of late-stage malaria-infected erythrocytes resulted in a large
      (nitrendipine-sensitive) increase in K+(86Rb+) influx. These results suggest that
      the endogenous Ca(2+)-activated K+ channel remains inactive in human red cells
      infected with late-stage parasites. The identity of the pathway which mediates
      the increased K(+)-leak in infected erythrocytes remains to be established.

PMID- 1375511
TI  - Discordant regulation of human type I collagen genes by prostaglandin E2.
AB  - We examined the expression of type I collagen genes in prostaglandin E2 (PGE2)
      treated human lung fibroblast cultures. Addition of PGE2 to fibroblast cultures
      inhibited alpha 1(I) mRNA levels by approx. 25% after 6 h and 60% after 24 h.
      Further studies showed that dibutyryl cAMP did not inhibit alpha 1(I) mRNA levels
      and that cycloheximide blocked the inhibitory effect of PGE2. In contrast, PGE2
      treatment with or without cycloheximide did not affect alpha 2(I) mRNA levels.
      Moreover, in vitro translation of RNA derived from untreated and PGE2-treated
      cells yielded similar amounts of alpha 2(I) collagen peptides. Taken together,
      these results suggest that PGE2 induces a protein which inhibits alpha 1(I)
      transcription through distinct regulatory elements not under the control of cAMP
      and provide further evidence that the type I collagen genes can be discordantly
      regulated.

PMID- 1375513
TI  - Invasion and metastasis.
AB  - Tumor metastasis remains a major cause of death for cancer patients. From a
      clinical perspective, treatment of metastatic disease remains difficult. The
      initial tumor cell invasive and locomotive events have been completed in many
      patients by the time of cancer diagnosis and surgery. This observation focuses
      attention on the last steps in the metastatic cascade for therapeutic
      development, ie, angiogenesis and colonization at the metastatic site. Emerging
      themes in metastasis research, including the molecular characterization of
      protease production and angiogenesis, the interrelationship of growth and
      metastasis, and the genetic control of the metastatic process are discussed.

PMID- 1375514
TI  - Expression of a glyceraldehyde 3-phosphate dehydrogenase gene specific to mouse
      spermatogenic cells.
AB  - A cDNA clone encoding a putative glyceraldehyde 3-phosphate dehydrogenase (GAPD
      S) protein specific to spermatogenic cells was isolated from a mouse
      spermatogenic cell expression library. The Gapd-s cDNA contained 1451 bp of
      transcribed sequence, including an ATG initiation codon and a poly(A) addition
      signal. The location of the Gapd-s initiation codon differed from that of other
      Gapd sequences, resulting in a germ cell GAPD-S protein predicted to contain 105
      additional residues at the amino terminus. While GAPD is constitutively expressed
      in somatic tissues, Northern blot analysis demonstrated that a Gapd-s probe
      hybridized to a 1.5-kb transcript present only in the testis. The Gapd-s mRNA was
      first detected during postnatal development in the testes of 20-day-old mice,
      suggesting that gene expression begins shortly after the appearance of haploid
      round spermatids. Northern analysis of RNA from isolated mouse pachytene
      spermatocytes and spermatids confirmed that Gapd-s expression is confined to post
      meiotic germ cells. GAPD has been previously proposed to be the key enzyme
      regulating glycolysis in isolated round spermatids. We hypothesize that the GAPD
      S enzyme plays an important role in regulating the switch between different
      pathways for energy production during spermiogenesis and in the spermatozoon.

PMID- 1375515
TI  - Prostaglandin synthesis regulation in human amnion tissue: involvement of protein
      kinase C and dependence on ribonucleic acid and protein synthesis.
AB  - The role of protein kinase C (PKC) in the control of prostaglandin production by
      the human amnion was studied. Amnion membranes delivered spontaneously at term
      were minced and treated with phorbol esters, protein kinase inhibitors,
      cycloheximide, and actinomycin D; prostaglandin E2 (PGE2) output then was
      determined. Untreated tissue produced 3.97 +/- 1.13 ng PGE2/micrograms DNA/14 h
      (mean +/- SEM, n = 19). Phorbol dibutyrate and 12-O-tetradecanoylphorbol-13
      acetate (TPA) stimulated PGE2 output up to 20-fold in a concentration-dependent
      manner with potencies corresponding to their efficacy as PKC activators. Four
      beta-phorbol and 4-methoxy-TPA, which do not stimulate PKC, did not affect PGE2
      output. Stimulation by TPA was blocked by staurosporine (IC50 = 57 nM) and H7;
      however, these PKC inhibitors did not decrease basal prostaglandin production.
      Cycloheximide inhibited basal and TPA-promoted PGE2 production and amino acid
      incorporation. Actinomycin D abolished TPA stimulation without decreasing
      unstimulated prostaglandin synthesis. These results show that amnion PGE2
      production after labor is not maintained by PKC action, but PKC activation in
      this tissue causes a protein synthesis-dependent and RNA synthesis-dependent
      increase of PGE2 output. However, basal PGE2 production is dependent upon protein
      synthesis which, presumably, utilizes pre-existing mRNAs.

PMID- 1375517
TI  - Native epitopes of human IgA.
AB  - We have studied the epitopes of the human IgA molecule by using 27 monoclonal
      antibodies in two simple gel diffusion methods. By testing pairs of monoclonal
      antibodies for coprecipitation of an IgA myeloma protein, we have clearly
      identified sterically independent epitopes on the molecule. By testing the non
      coprecipitating monoclonal antibodies with soluble IgA-monoclonal antibody immune
      complexes, we have identified the overlapping epitopes. Eleven proto-epitopes
      were mapped on the IgA molecule. Since we have not used solid-phase methods, we
      have presumably identified native epitopes of the IgA molecule.

PMID- 1375516
TI  - Fluid transport in a cultured cell model of kidney epithelial cyst enlargement.
AB  - Madin-Darby canine kidney (MDCK) cells, when seeded into collagen gel, from
      polarized, spherical, epithelial cysts, which grow by a process involving fluid
      secretion and cell proliferation. These cysts are a useful model for
      understanding the dynamics of cyst enlargement in renal cystic disease. The
      hypothesis that MDCK cyst fluid secretion depends upon chloride secretion was
      tested, and a cell model for this process is presented here. Lumen and epithelial
      cell volumes were measured by video microscopy in acute experiments. Fluid
      absorption (-0.073 +/- 0.007 microliters.h-1.cm-2; N = 8) was observed when cysts
      were superfused with unsupplemented Dublecco's modified Eagle's medium at 36 to
      37 degrees C. Fluid secretion (0.221 +/- 0.0016 microliters.h-1.cm-2; N = 25) was
      seen when 1 mM dibutyryl cAMP plus 0.1 mM 3-isobutyl-1-methylxanthine were added
      to the superfusate. cAMP-induced fluid secretion was significantly inhibited by
      basolateral 1 mM ouabain, 0.1 mM furosemide, or 1 mM amiloride. It was not
      significantly affected by 1 mM chlorothiazide, 0.01 mM bumetanide, or 0.1 mM
      acetazolamide in the presence of normal bicarbonate/CO2. In the nominal absence
      of bicarbonate/CO2 fluid secretion was 18% of control. Vasopressin-induced fluid
      secretion was significantly inhibited by pretreatment of cysts with 0.1 mM 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Cyst cell shrinkage in
      isosmotic chloride-free Ringer's solution (chloride replaced by gluconate) was
      inhibited by 0.1 mM basolateral DIDS. The results suggest that chloride
      bicarbonate exchange in the basolateral membrane of MDCK cyst epithelial cells
      plays a critical role in cyst fluid secretion.

PMID- 1375518
TI  - Antigen-independent pathways of T-cell activation are functional in human
      immature thymocytes.
AB  - The signal requirements for proliferation of CD1+CD3- immature thymocytes have
      been studied in order to define whether this immature cell population could
      function despite the lack of the CD3/T-cell receptor complex. We found that
      CD1+CD3- cells proliferate upon stimulation with anti-CD28 monoclonal antibody as
      well as with a pair of anti-CD2 monoclonal antibodies in the presence of low
      doses (0.5 ng/ml) of phorbol-13-myristate-12-acetate and/or recombinant
      interleukin-2. A minor fraction of CD3+ cells (15%-20%) was also present in the
      proliferating cell population originating from CD1+CD3- thymocytes stimulated
      with phorbol-13-myristate-12-acetate and recombinant interleukin-2, either in the
      presence or in the absence of specific monoclonal antibodies. We further observed
      that the anti-CD3 monoclonal antibody did not induce the proliferation of CD1+CD3
      cells, as expected, and efficiently triggered unfractionated or CD1+CD3+
      thymocytes only if exogenous recombinant interleukin-2 was provided.
      Unexpectedly, we noted that highly purified (greater than 99%), CD1+CD3- immature
      thymocytes could mobilize calcium via CD3, besides CD2 and CD28 surface
      molecules, suggesting that a minor undetectable fraction (less than 1%) of CD3+
      cells was still present in the purified CD3- population. Nevertheless, the
      preferential expansion of CD3-CD8+ cells (about one-third of proliferating cells)
      after triggering via CD28, and to a lesser extent via CD2, support the notion
      that the alternative pathways of T-cell activation are actually functional in
      CD1+CD3- immature thymocytes.

PMID- 1375519
TI  - A combined pseudoreplica-immunochemical technique for research and diagnostic
      virology.
AB  - Pseudoreplica and immunochemical techniques were combined in a single protocol
      for identification of virus in research and clinical specimens. Stock
      preparations of vesicular stomatitis virus (VSV), cytomegalovirus (CMV), and
      herpes simplex virus (HSV) were used to develop the technique. Traditional
      pseudoreplicas of viral stock solutions were prepared but not negatively stained.
      The virus was then immunolabeled in two stages. Virus-specific polyclonal
      antisera were used in the first stage; colloidal gold conjugated antibodies were
      used as indicator antibody in the second stage. After immunolabeling, the grids
      were negatively stained. As a demonstration of the clinical usefulness of this
      approach, it was employed to antenatally identify human parvovirus B19 particles
      in ascites from a 22 week gestational fetus with nonimmune hydrops fetalis. The
      combined pseudoreplica-immunochemical approach offers several advantages over
      both the pseudoreplica and immunochemical methods when used in isolation.
      Advantages include relative purification of samples, concentration of virus,
      morphological preservation, and enhanced diagnostic specificity.

PMID- 1375521
TI  - Doxycycline as a sclerosing agent.

PMID- 1375520
TI  - Section staining for electron microscopy using tannic acid as a mordant: a simple
      method for visualization of glycogen and collagen.
AB  - The possibility that tannic acid and other classical mordants can be used in the
      electron microscopical section staining technique has been tested. A mordant can
      be defined as a chemical that combines with both a certain specific tissue
      component and the staining substance and thereby permits a staining reaction that
      otherwise will not be obtained. The following features were found to characterize
      section staining of tannic acid mordanted sections. Tannic acid apparently blocks
      those sites that normally would be contrasted by uranyl acetate or some other
      staining compounds. Ribosomes remain unstained. Glycogen particles, on the other
      hand, were stained, whereas they are not in non-mordanted sections. In fact,
      glycogen was the only cytoplasmic component to be contrasted by the uranyl
      acetate, and collagen the only extracellular component. Several different section
      staining solutions gave the same staining patterns of examined cells and tissues.
      Specificity of the reaction thus seems to depend on the mordant rather than on
      the heavy atom section stain. Some other tested mordants, which have also been
      used in the light microscopical technique, did not give any useful new
      information.

PMID- 1375522
TI  - Mechanisms contributing to ozone-induced bronchial hyperreactivity in guinea
      pigs.
AB  - The effect of ozone (3 ppm, 15-120 min) on bronchial reactivity in the guinea-pig
      was studied. Ozone induced marked (6-250-fold) bronchial hyperreactivity (BHR) to
      a range of inhaled, but not intravenous bronchoconstrictors. The degree of BHR
      was related to the duration of prior ozone exposure. The glutathione redox status
      was shifted to a more oxidized state in lung after 120 min ozone treatment,
      although no changes were found in the energy status of lung tissue, as judged by
      the concentrations of adenosine phosphates. Ascorbic acid pretreatment prevented
      BHR induced by 30 min ozone exposure. Neutral endopeptidase inhibitors elicited
      BHR to both substance P and histamine, but did not further enhance
      bronchoconstriction to substance P after ozone exposure for 120 min. Neither
      mepyramine, fentanyl, indomethacin nor a 5-lipoxygenase inhibitor (BW B70C),
      given prior to ozone exposure prevented the induction of BHR to histamine.
      Atropine or bilateral vagotomy reduced BHR after a 120-min, but not 30-min
      exposure to ozone. We conclude that in the guinea-pig, ozone induces non
      specific, route-dependent BHR by oxidative injury, reducing airway NEP activity
      and enhancing the cholinergic and peptidergic component to bronchoconstriction.
      Neither cyclooxygenase nor 5-lipoxygenase products appear to play a role in ozone
      induced BHR in this animal model.

PMID- 1375523
TI  - Respiratory failure without pulmonary edema following injection of a glutamate
      agonist into the ventral medullary raphe of the rat.
AB  - Injection of ibotenic acid (IA), a glutamate agonist, into the ventral medullary
      raphe (VMR; especially the nucleus raphe magnus) of the rat produced respiratory
      failure and death following a predictable course of events. The response to the
      IA injection was characterized initially by increased respiratory frequency and
      was followed by pulmonary arterial hypertension, systemic arterial hypoxemia,
      acidosis, and hypothermia. Within 90 min apnea occurred as a terminal event in
      all animals. Gravimetric, bronchoalveolar lavage protein, and histological
      analyses revealed no evidence of pulmonary edema. Intracerebral (VMR)
      pretreatment with PPP, a sigma receptor agonist, or scopolamine, a muscarinic
      cholinergic antagonist, prevented pulmonary failure and death even though
      postmortem histological analysis showed VMR cell loss and gliosis consequent to
      the cytotoxic IA injection. Based on the results of the study, it is suggested
      that the VMR has a role in regulation of pulmonary blood flow. Preliminary
      pharmacological studies suggested that a disruption of glutamatergic and
      cholinergic mechanisms mediates the lethal pulmonary phenomenon.

PMID- 1375524
TI  - Paraoxon block of chloride conductance in cell R2 of Aplysia californica.
AB  - In the presence of paraoxon, the amplitudes of chloride currents activated by
      acetylcholine (ACh) or gamma-aminobutyric acid (GABA) were reduced in cell R2 of
      Aplysia californica. IC50 values were 12 and 9.7 microM for ACh and GABA
      responses, respectively. Paraoxon did not affect resting membrane potential,
      input resistance, or chloride reversal potential. Both the slopes and maxima of
      ACh and GABA concentration-response curves were reduced by paraoxon, suggesting
      that paraoxon antagonism of these responses is not competitive. The antagonism of
      ACh and GABA responses by paraoxon was not related to inhibition of
      acetylcholinesterase.

PMID- 1375525
TI  - Induction of expression of genes encoding transcription factors in the rat brain
      elicited by behavioral training.
AB  - c-fos and zif/268 are regulatory genes encoding transcription factors able to
      influence gene expression directly. It has been shown repeatedly that expression
      of transcription factors correlates with different forms of cell activation,
      probably being functionally involved in the coupling of extracellular signals
      with long-term cellular responses. This study describes that c-fos and zif/268
      mRNA accumulation, as measured by northern blot analysis, occurs in the rat
      hippocampus as well as the visual cortex following behavioral training of two-way
      active avoidance response.

PMID- 1375526
TI  - Extendable words in nucleotide sequences.
AB  - Previous statistical analyses revealed several peculiarities of nucleotide
      sequences that preclude their description by existing models and thus allow one
      to distinguish DNA and RNA sequences from random A,T,G,C-texts. This is a
      consequence of the unusual distribution of certain words in nucleotide sequences:
      while the distribution of (most) words is consistent with Markov models of small
      orders, the distribution of certain words cannot be described by any previous
      model (anomalies in distribution of homonucleotide/homopurine/homopyrimidine
      runs, complementary and mirror palindromes, and non-stationary words). In this
      work we introduce a probabilistic approach that is partly motivated by analogy
      with linguistics. We also describe another important feature of DNA/RNA
      sequences: anomalies in distribution of words of poor nucleotide composition. We
      show that some classes of these words are the major obstacle for the simple
      Markov description of nucleotide sequences.

PMID- 1375527
TI  - Brief chemotherapy, involved field radiation therapy, and central nervous system
      prophylaxis for paranasal sinus lymphoma.
AB  - Lymphoma of the paranasal sinus is a rare tumor characterized by bulky local
      disease, early systemic dissemination, and a propensity for central nervous
      system (CNS) spread. Treatment with radiation alone generally has been
      disappointing. Based on previous encouraging reports of initial brief
      chemotherapy followed by involved field radiation therapy (IFRT) for localized
      large cell lymphoma, four consecutive patients with paranasal sinus lymphoma were
      treated with 6 weeks of chemotherapy followed by IFRT and CNS prophylaxis. All
      patients had bulky localized disease and diffuse large cell lymphoma. Complete
      response was seen in all patients, and none have had a relapse (minimum follow
      up, 25 months; range, 25 to 32 months). Chemotherapy and radiation therapy were
      well tolerated. One patient developed an osteogenic sarcoma in the radiation
      field 32 months after completion of therapy. Administration of early frequent
      chemotherapy followed by IFRT and CNS prophylaxis appears to be an effective
      treatment strategy for patients with localized large cell lymphoma of the
      paranasal sinuses.

PMID- 1375528
TI  - Detection of a novel marker in the bronchial secretions of patients with non
      small cell lung cancer using the 4B5 monoclonal antibody.
AB  - A murine monoclonal antibody designated 4B5 was raised against the high molecular
      weight fraction of pooled sputum from patients with non-small cell lung cancer
      (NSCLC). Immunohistochemical staining indicated that 4B5 binds to histologically
      normal bronchial epithelium distant from tumor in 72% (39 of 54) of patients with
      NSCLC, but it binds to the primary cancer in only 13% (7 of 54) of the same
      patients. The antibody reacted less intensely with the bronchial epithelium in
      16.6% (3 of 18) of autopsied patients without significant lung disease. The
      antigen recognized by 4B5 is a high molecular weight glycoprotein of more than
      400 kilodaltons, judged by gel filtration and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and western blot analysis. Antigenic activity
      persisted after heating and resisted treatment with neuraminidase, but it was
      destroyed using protease and periodate. Multiple epitopes were present on each
      molecule recognized by 4B5. The determinants recognized by this antibody deserve
      additional study as possible markers of premalignant change in patients with
      NSCLC.

PMID- 1375529
TI  - X-linked gene MIC5 codes for the L1 adhesion molecule recognized by monoclonal
      antibody R1.
AB  - Monoclonal antibody (MoAb) R1 was generated by use of human-mouse hybrids
      containing only the long arm of chromosome X as the human component. It
      recognizes plasma membrane glycoproteins of 145 and 200 kd as well as a soluble
      protein of 195 kd. In this study, using a biochemical approach, we identified
      these glycoproteins as the human L1 adhesion molecule.

PMID- 1375530
TI  - Heterozygote detection through bleomycin-induced G2 chromatid breakage in
      dyskeratosis congenita families.
AB  - We determined the mean number of chromatid breaks per cell (b/c) in the bleomycin
      treated lymphocytes of 10 patients with dyskeratosis congenita (DC) and 26 of
      their relatives to ascertain whether bleomycin sensitivity would distinguish DC
      heterozygotes from normal individuals. We observed a significantly higher mean
      number of chromatid b/c in DC patients and obligate heterozygotes (patients
      versus controls, p less than 0.0001; heterozygotes versus controls, p = 0.0076,
      Mann-Whitney rank-sum test). Unequivocal heterozygote detection was not possible
      owing to overlap of the b/c values of patients, heterozygotes, and controls, but
      our findings provided strong evidence of a link between autosomal recessive as
      well as X-linked recessive DC mutations and bleomycin sensitivity in homozygous,
      hemizygous, and heterozygous individuals.

PMID- 1375531
TI  - Translocation (2;9)(p12;p23) in a case of acute leukemia with t(4;11)(q21;q23).
      Lack of rearrangement of the kappa and interferon gene loci.
AB  - A case is reported of an adult male patient with acute leukemia characterized by
      the presence of the novel cytogenetic abnormality, t(2;9)(p12;p23), in addition
      to a t(4;11)(q21;q23). The immunophenotype of the blast cell population was
      consistent with immature early pre-B cell acute lymphoblastic leukemia (ALL)
      (TdT+,HLA-DR+,CD19+,CD24 +/-,CD10-) expressing myelo-monocytic antigens
      (CDw65,CD15). The genotype showed a clonal rearrangement of the immunoglobulin
      heavy chain locus. Because the immunoglobulin kappa (kappa) light chain gene is
      located on chromosome 2 at band p12 and interferon alpha (alpha) and beta (beta)
      map to chromosome 9p21-p22, rearrangements of these loci as a result of the
      t(2;9) were studied. There was no evidence for rearrangement of the region
      covering about 40 kilobases around the kappa locus when hybridized to C(kappa),
      the 3' kappa enhancer or the kappa deleting element. Only germline size
      restriction fragments were also found for the interferon alpha and beta genes.
      The patient's clinical features were typical for ALL associated with the t(4;11),
      including a high white blood cell count at presentation, hepatosplenomegaly, and
      a poor outcome. The potential significance of 2p and 9p abnormalities in addition
      to t(4;11) is discussed.

PMID- 1375532
TI  - Modulation of trenimon-induced cytotoxicity by DT-diaphorase in isolated rat
      hepatocytes under aerobic versus hypoxic conditions.
AB  - Trenimon belongs to a class of aziridinylbenzoquinone anticancer drugs that cross
      the blood-brain barrier. In this study we have investigated the molecular
      mechanisms for trenimon-induced toxicity in aerobic versus hypoxic conditions
      with the use of freshly isolated rat hepatocytes. The following evidence suggests
      the mechanisms for trenimon detoxification involves reduction by DT-diaphorase,
      while the cytotoxic mechanism involves macromolecular alkylation under hypoxic
      conditions as well as oxidative stress under aerobic conditions. (a) Hepatocyte
      cytotoxicity induced by trenimon (250 microM) under aerobic conditions ensued
      following an initial induction of cyanide-resistant respiration and partial
      oxidation of glutathione to oxidized glutathione. Trenimon reduction to the
      hydroquinone by the hepatocytes was rapid. Inhibition of hepatocyte DT-diaphorase
      by dicumarol increased trenimon-induced cytotoxicity by approximately 10-fold,
      and markedly inhibited hydroquinone formation. Furthermore, both cyanide
      resistant respiration and oxidized glutathione formation were markedly increased,
      resulting in depletion of oxygen in the media. Trenimon reduction to the
      hydroquinone then occurred. This suggests that DT-diaphorase in normal
      hepatocytes prevents the formation of the semiquinone that causes cytotoxic
      protein alkylation and oxidative stress. (b) Hepatocyte cytotoxicity induced by
      trenimon (350 microM) under hypoxic conditions ensued following glutathione
      depletion without oxidized glutathione formation. Inactivation of hepatocyte DT
      diaphorase by dicumarol under hypoxic conditions increased trenimon-induced
      cytotoxicity by approximately 3.5-fold and increased semiquinone radical levels 2
      fold without affecting its reduction rate. This suggests that the cytotoxic
      mechanism involves protein alkylation by semiquinone radicals formed by
      reductases catalyzing a one-electron reduction of trenimon.

PMID- 1375534
TI  - Efficacy of an anti-CD7-ricin A chain immunoconjugate in a novel murine model of
      human T-cell leukemia.
AB  - In vivo efficacy testing of monoclonal antibody-based drugs specific for human
      leukemias is hampered by the paucity of suitable animal models, due in part to
      the inability of many anti-human monoclonal antibodies to cross-react with
      antigens expressed in animal tissues or cells. Moreover, human leukemic cells
      have proven difficult to establish in immunosuppressed mice except as solid
      tumors. We report here the establishment of a murine model for human leukemia
      displaying features of human disease, such as growth of malignant cells and
      localization of such cells to lymphoid compartments, and the effective depletion
      of leukemic cells from these mice by an immunoconjugate. Human T-leukemia cells
      (CEM) injected into cyclophosphamide-pretreated NIH-III mice engrafted in all
      mice (n = 41), with CEM cells detected in the bone marrow, spleen, and blood 4
      weeks after injection. There was no evidence of solid tumors. Treatment of CEM
      engrafted mice with 4A2-RTA30, an immunoconjugate of an anti-CD7 monoclonal
      antibody and ricin A chain (RTA30), resulted in a 100- to 200-fold overall
      depletion of CEM cells from the spleen and the bone marrow (P less than 0.02).
      This depletion was specific and toxin-dependent, as a control immunoconjugate had
      no demonstrable effect (P greater than 0.5). Depletion of CEM cells was also
      observed after treatment with unconjugated anti-CD7 mAb, but this effect was not
      significantly different from controls (P greater than 0.1). Therefore,
      significant depletion of CEM cells required the presence of the ricin A chain
      moiety. Further investigations revealed that CEM cells recovered from NIH-III
      mice expressed less CD7 antigen, but remained sensitive to subsequent in vitro
      exposure to 4A2-RTA30. In conclusion, we have established a model for studying
      the efficacy of immunoconjugates and have successfully depleted human T-leukemic
      cells from lymphoid tissues in immunodeficient mice by treatment with an anti-CD7
      RTA30 immunoconjugate.

PMID- 1375533
TI  - Endogenous receptor-bound urokinase mediates tissue invasion of the human lung
      carcinoma cell lines A549 and Calu-1.
AB  - Macrophage colony-stimulating factor (CSF-1) increases the tissue invasive
      potential of the CSF-1 receptor-bearing lung carcinoma cell lines A549 and Calu-1
      by increasing the number of endogenously bound urokinase-type plasminogen
      activators (u-PA)s on these cells. CSF-1, at concentrations which optimize
      invasion of A549 and Calu-1 cells into human amnion membranes (250 ng/ml),
      maximally augments the number of u-PA receptors occupied by endogenously produced
      urokinase. Preincubation of A549 and Calu-1 cells with the anti-u-PA monoclonal
      antibody MPW5UK (25 micrograms/ml) or with a 20- to 40-fold stoichiometric excess
      of fluid phase type 2 plasminogen activator inhibitor abrogates invasiveness,
      indicating that functionally active cell surface u-PA is essential for tissue
      invasion. In contrast, fluid phase type 1 plasminogen activator inhibitor (PAI-1,
      5-15 units/ml) does not inhibit invasiveness unless preincubated with the amnion
      membranes. Inhibition of invasion by PAI-1 is abolished by presaturating the
      amnion membranes with antiitronectin monoclonal antibody (10 micrograms/ml) which
      prevents binding of PAI-1 to tissue-associated vitronectin. Binding of PAI-1 to
      tissue vitronectin is therefore a prerequisite for its inhibitory action. Thus,
      endogenously receptor-bound u-PA is the primary protease mediating CSF-1-induced
      tissue invasiveness of the lung carcinoma cell lines A549 and Calu-1.

PMID- 1375535
TI  - Development of an in vitro model to study carcinogen-induced neoplastic
      progression of initiated mouse epidermal cells.
AB  - Initiation and promotion in mouse skin carcinogenesis produce multiple benign
      tumors, squamous papillomas, but only a few squamous cell carcinomas. The
      spontaneous conversion from the benign to the malignant phenotype occurs over
      many months and in stages, but induced malignant conversion can be accomplished
      more rapidly by exposure of papilloma-bearing mice to mutagens or by transfection
      of papilloma cell lines with specific oncogenes. The analysis of genetic targets
      responsible for carcinogen-induced neoplastic progression would be facilitated by
      the development of in vitro models where the process is rapid, focal, and
      quantitative. To this end, primary newborn mouse keratinocytes were initiated in
      vitro by the introduction of the v-rasHa oncogene via a defective retrovirus.
      Recipient cells produce squamous papillomas and have a high proliferation rate in
      culture medium with 0.05 mM Ca2+, but fail to grow in medium with 0.5 mM Ca2+
      which is permissive for growth of malignant keratinocytes. When v-rasHa
      keratinocytes were exposed to mutagens in vitro, proliferative foci emerged after
      culture in 0.5 mM Ca2+ for 4 weeks. These foci stained intensely red with
      rhodamine stain, could be easily quantitated, and readily incorporated
      bromodeoxyuridine. Dose-response studies with several mutagens indicated that the
      number of foci increased with concentration to the point where excessive
      cytotoxicity developed. Mutagens varied in potency for producing foci in the
      following order: cis-diamminedichloroplatinum greater than or equal to
      benzo(a)pyrene diolexpoxide I greater than N-methyl-N'-nitro-N-nitrosoguanidine
      greater than or equal to 4-nitroquinoline-N-oxide greater than N-acetoxy-acetyl-
      aminofluorene. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate was
      inactive in the assay. A subset of cell lines derived from foci produced
      malignant tumors in vivo, while others were not tumorigenic. Analysis of DNA from
      cell lines and tumors revealed that most tumorigenic cell lines maintained the v
      rasHa genome, whereas the viral sequences were deleted in nontumorigenic cell
      lines. Immunohistochemical analysis indicated that proliferative foci and
      quiescent v-rasHa keratinocytes expressed keratin 8, a marker of v-rasHa
      expression in cultured keratinocytes. Cells in foci, but not v-rasHa control
      cells, expressed keratin 13, a marker which is strongly associated with the
      malignant progression of skin tumors in vivo. This in vitro assay provides a
      quantitative model to study chemically induced focal neoplastic progression at
      the cellular level and to identify agents which may be selective for enhancing
      malignant conversion.

PMID- 1375536
TI  - Potential autocrine role of insulin-like growth factor II during suramin-induced
      differentiation of HT29-D4 human colonic adenocarcinoma cell line.
AB  - Suramin, a drug that binds to several types of growth factors, has been
      previously shown to induce the enterocyte-like differentiation of HT29-D4 human
      colonic adenocarcinoma cells, suggesting that growth factors are involved in such
      a process. Undifferentiated HT29-D4 cells release insulin-like growth factor II
      (IGF-II) into the culture medium that is totally complexed to heterogeneous IGF
      binding proteins (IGFBP) expressing high affinities for this growth factor (Kda =
      0.02 nM and Kdb = 1.4 nM). These complexes do not allow IGF-II to bind to HT29-D4
      cell surface type I IGF receptors, as evidenced by using 125I-IGF-II-IGFBP
      complexes. However, the addition of 40-100 micrograms/ml suramin, i.e.,
      concentrations identical to the ones that are able to induce HT29-D4 cell
      differentiation, induces the release of IGF-II from IGF-II-IGFBP complexes,
      thereby allowing IGF-II to bind to the cell surface receptors. At such
      concentrations, suramin is indeed unable to alter IGF-II binding to HT29-D4
      cells, a capacity that is observed only for concentrations higher than 200
      micrograms/ml. Thus, suramin might have the unusual capacity to allow the
      establishment of an IGF-II autocrine loop involved in HT29-D4 cell
      differentiation. Consistent with this hypothesis is the fact that exogenously
      applied IGF-I (2.5 micrograms/ml) or agonist monoclonal antibody alpha IR-3 (2.5
      micrograms/ml), which can bypass IGFBP present in the culture medium, induces
      part of HT29-D4 cell differentiation that is characterized by an important
      carcinoembryonic antigen release and the induction of numerous intercellular
      cysts with microvilli.

PMID- 1375537
TI  - Cinnarizine-induced parkinsonism in primates.
AB  - We describe the production of an experimental model of parkinsonism induced by
      cinnarizine (CNZ) in three healthy sylvanna monkeys. The drug produced a severe
      but reversible parkinsonism in all animals. After discontinuation of CNZ, all
      animals recovered but the oldest one was akinetic for 6 weeks. CNZ produced a
      persistent reduction in HVA and 5-HIAA levels in the CSF. Our data suggest a
      predominant presynaptic effect on DA and 5-HT neurons; and could account for the
      longstanding parkinsonism induced by calcium antagonist in some patients as well
      as the depression observed in these subjects.

PMID- 1375538
TI  - Plasma beta-endorphin levels and natural-killer cells in two cases of congenital
      indifference to pain.
AB  - We have investigated plasma beta-endorphin (beta-E), ACTH, and cortisol in two
      cases of congenital indifference to pain (CIP), a rare syndrome characterized by
      unresponsiveness to painful stimuli. As the two patients had frequent skin
      infections, we also studied lymphocyte response to mitogens in the absence or
      presence of beta-E. In addition, we explored a series of lymphocyte membrane
      antigens related to different aspects of the immune response, such as CD3+, CD4+,
      CD8+, B, NK Leu 7, Leu 9, and Leu 19, anti-interleukin-2 receptor (anti-TAC).
      Plasma beta-E levels in the two patients were significantly higher than in
      controls, whereas plasma ACTH and cortisol levels were normal. Lymphocyte
      response to the mitogen phytohemagglutinin was normal. The expression of Leu 7,
      Leu 9, and Leu 19, three antigens related to natural killer cells, was decreased
      by about 50%. The results indicate that in the two cases of CIP studied, high
      plasma beta-E levels are associated with a reduction in the expression of natural
      killer cells. This suggests that the two phenomena are specifically related to
      each other. These data represent further evidence of the possible
      pathophysiological relevance of the neuroendocrine-immune feedback.

PMID- 1375540
TI  - [Effect of 764-3 on bleomycin activation of alveolar macrophages].
AB  - The effect of pretreatment with 764-3, a huo xue hua yu medicine, on bleomycin A6
      activation of alveolar macrophages of rats was observed. Results showed that
      bleomycin A6 could activate alveolar macrophages directly and that 764-3 could
      inhibit the activating effect of bleomycin A6. When alveolar macrophages are
      activated, they release not only PMN chemotactic factor, but also many
      destructive lysosomal enzymes, superoxide anions, etc, possibly resulting in
      serious injury to the lungs.

PMID- 1375539
TI  - Tracing the roots of ion channels.
AB  - Two sets of recent findings draw our attention to questions concerning the origin
      of ion channels. First, there is sequence similarity among five classes of
      channels: voltage-gated channels, a putative Ca(2+)-activated K+ channel, cyclic
      nucleotide-gated cation channels, a putative Ca2+ channel for phosphoinositide
      mediated Ca2+ entry, and a plant K+ channel/transporter. Like voltage-gated K+
      channels, the most recently identified members of the superfamily share the basic
      design of one set of six potential membrane-spanning segments plus the H5
      sequence; as such, they may resemble more closely the ancestral channel, which is
      likely to predate the separation of the animal and plant kingdoms. Second,
      several members of the ABC superfamily function as ion channels, even though they
      were previously known as transporters or enzymes. Did some ancestral enzymes
      subsequently acquire channel/transporter function? Or could it be the other way
      around? Aside from evolutionary considerations, enzymes and ion channels can no
      longer be treated as separate and nonoverlapping groups of proteins. When one
      molecule exhibits both functions, there are interesting mechanistic questions:
      How might the enzyme activity such as ATP hydrolysis be coupled to
      activation/regulation of the intrinsic channel activity? How might interactions
      between the permeant ions and the channel pore in turn regulate the enzymatic
      function of the same molecule? It seems possible that the latter is an extension
      of the observed coupling between permeant ions and the gating machinery of an ion
      channel (Swenson and Armstrong, 1981). Finally, the potential cross-regulation
      between channel activity and enzyme activity within the same molecule offers many
      intriguing possibilities for the integration of different cellular functions.

PMID- 1375541
TI  - [Effect of 764-3 on histamine content in the lungs during inflammation and on the
      proliferation of lung fibroblasts].
AB  - The changes of histamine content in inflamed lungs induced by bleomycin, lung
      fibroblast proliferation enhanced by histamine and the effect of 764-3 on these
      parameters were investigated. Results showed that: 1) after intratracheal
      instillation of bleomycin for 7 and 21 days, the lung histamine content increased
      significantly, and 764-3 inhibited this increase of histamine content; 2)
      histamine enhanced the proliferation of lung fibroblasts in a dose- and time
      dependent manner, and 764-3 inhibited the proliferation of lung fibroblasts in
      both normal and histamine-enhanced conditions. Results suggested that both
      inhibitory actions (direct inhibition of fibroblast proliferation and indirect
      action stemming from a reduction in the histamine content increase) might be
      involved in the antifibrotic mechanism of 764-3.

PMID- 1375542
TI  - 3-Methylglutaconic aciduria in two adults.

PMID- 1375543
TI  - Interstrain cross-reactive idiotypes on monoclonal antibodies to an
      encephalitogenic myelin basic protein peptide.
AB  - In order to assess the role of idiotype (Id) and the anti-Id network in murine
      experimental autoimmune encephalomyelitis (EAE), Id-bearing monoclonal antibodies
      (mAb) to human myelin basic protein (MBP) peptide acetyl 1-9, as well as mAb anti
      Id, were developed in EAE-susceptible PL/J mice (H-2u). These mice recognize MBP
      residues acetyl 1-9 as an encephalitogenic determinant. Reactivities of PL/J Id
      bearing mAbs to MBP and to MBP peptides were identical to those of mAbs generated
      against the same MBP peptide in EAE-resistant BALB/c mice (H-2d), even though
      isotypes of the mAbs differed. By using an inhibitory ELISA and immunoblotting,
      it was demonstrated that one PL/J mAb anti-Id recognized a public or framework
      Id, whereas another PL/J mAb-anti Id was directed to a private Id more restricted
      to the paratopic site. Two Id-bearing PL/J mAbs shared a cross-reactive Id (IdX)
      on the light chain, and an interstrain IdX was present on both the heavy and
      light chains of mAbs raised in PL/J and BALB/c mice to the same MBP peptide. The
      PL/J mAb anti-Id was capable of cross-regulating the production of Id-bearing
      mAbs by hybridomas across murine strains. These findings suggest that a
      restrictive family of germ-line genes encode for these Id-bearing antibodies to
      MBP peptide, irrespective of whether the MBP peptide is encephalitogenic in the
      murine strain immunized. Manipulation of the Id network may provide a means for
      modifying autoimmune demyelinating diseases of the central nervous system.

PMID- 1375544
TI  - The role of neuropeptides in asthma.

PMID- 1375545
TI  - Hair follicle differentiation: expression, structure and evolutionary
      conservation of the hair type II keratin intermediate filament gene family.
AB  - During hair follicle development several cell streams are programmed to
      differentiate from the cell population of the follicle bulb. In the hair cells, a
      number of keratin gene families are transcriptionally activated. We describe the
      characterization of the type II keratin intermediate filament (IF) gene family
      which is expressed early in follicle differentiation. In sheep wool, four type II
      IF proteins are expressed. One gene has been completely sequenced and the
      expression of three of the genes examined in detail. The sequenced gene encodes a
      55 x 10(3) Mr protein of the type II keratin IF protein family, designated KII-9
      in the new nomenclature we have adopted and described in the Introduction. The
      gene has a similar exon/intron structure to the epidermal type II keratin IF
      genes. In situ hybridization experiments show that the genes are expressed in the
      hair cortical cells but not in the cells of the outer root sheath, inner root
      sheath or medulla. During hair keratinocyte differentiation the type II IF genes
      are sequentially activated and coexpressed in the same cells. Expression is first
      detected in cells in the middle of the follicle bulb located near the dermal
      papilla and, subsequently, two of the genes are transcriptionally activated in
      the differentiating keratinocytes as they migrate upwards, in the upper part of
      the bulb. A fourth type II IF gene is activated later. The genes with the same
      expression pattern are also closely related in sequence and a number of conserved
      elements are present in the promoters of those genes, including a novel element
      which is also found in the promoter of a coexpressed type I IF gene and three
      other hair keratin genes.

PMID- 1375546
TI  - Multimodality imaging and intracranial EEG display for stereotactic surgery
      planning in epilepsy.
AB  - We describe a computer program for stereotactic surgery planning based on
      multimodality imaging and the display of intracranial EEG data in relation to
      anatomical data. The program is primarily designed to be used by surgeons to
      assist them in localizing brain structures and plan the safe and accurate
      insertion of surgical tools and depth electrodes. The mathematics underlying
      these concepts are briefly described. Estimates of the accuracy of the procedures
      are calculated and made available to the user. An extension of the program was
      developed to integrate intracranial EEG data with conventional images in order to
      help the neurologist and neurosurgeon in visualizing the EEG data in relation to
      the anatomy. It can be used to visualize the measured EEG voltages, or processed
      signals such as the application of the tetrahedral field calculation, which
      provides an extension of conventional bipolar EEG to 3 dimensions.

PMID- 1375547
TI  - Sequential EEG mapping may differentiate "epileptic" from "non-epileptic"
      rolandic spikes.
AB  - Sequential topographic mapping was performed to differentiate "epileptic" from
      "non-epileptic" rolandic spikes. Twenty-four children without any indication of
      organic brain lesion were divided into a group with epilepsy and a group without
      epilepsy. The group with epilepsy was subdivided into "classical BECT" (benign
      focal epilepsy of childhood with centro-temporal spikes) and "non-classical
      BECT." Sequential mapping of the rolandic spikes revealed two different
      topographic patterns: a pattern of stationary potential fields and a pattern of
      non-stationary potential fields. The topographic pattern of stationary potential
      fields was morphologically represented by a single spike-and-wave complex whereas
      that of non-stationary potential fields was morphologically represented by a
      "double" spike-and-wave complex. Among the non-stationary topographic patterns
      represented by a "double" spike, one specific sequence of changes of potential
      fields was found. This sequence started with a dipolar field, with the negative
      pole in the frontal region and the positive pole in the centro-temporal region,
      morphologically represented by the small first spike of the "double" spike-and
      wave complex. This dipolar field, changes to a unipolar or dipolar field, with a
      negative potential field in the centro-temporal region and, sometimes, a
      simultaneous positive potential field in the frontal region, morphologically
      represented by the prominent rolandic spike. This characteristic pattern was
      found to be significantly related to classical BECT.

PMID- 1375548
TI  - Regional coherence and the transfer of ictal activity during seizure onset in the
      medial temporal lobe.
AB  - Epileptiform activity requires that large aggregates of neurons act
      synchronously. The process of neuronal synchronization during seizure onset was
      studied in the human medial temporal lobe by measuring the coherence of EEG
      activity. Records were obtained from 10 consecutive patients with hippocampal
      depth electrodes being evaluated for possible resective surgery. Coherence and
      phase spectra were calculated from all possible pairs of contacts in the medial
      temporal lobe of seizure onset using the method of Gotman applied to successive
      6.4 sec epochs. Signals derived from adjacent contacts within definable brain
      regions were coherent during both the preictal and ictal period. Transitions in
      the level of coherence were measured between contacts presumed to span the
      boundaries of these regions. Time delays were measured early in the development
      of the seizure discharge but were not sustained. These time delays spanned the
      borders of regions of differing coherence, especially in the posterior
      hippocampus, and were interpreted to represent a transient increase in the
      functional linkage between structural elements. We conclude that the process of
      neuronal entrainment during seizure onset involves a transient interaction
      between brain regions but the maintenance of this interaction is not required for
      sustained seizure activity.

PMID- 1375549
TI  - Automatic EEG interpretation: a new computer-assisted system for the automatic
      integrative interpretation of awake background EEG.
AB  - A new computer-assisted system for automatic interpretation of the awake
      electroencephalogram (EEG) was developed. First, all the items necessary for EEG
      interpretation were determined in accordance with the procedure that a qualified
      electroencephalographer (EEGer) goes through for the visual inspection of the
      background EEG activity, and then each item was defined quantitatively. For the
      automatic interpretation, specific EEG parameters were determined for each item
      so that they could fit the graded judgement of the item by the qualified EEGer as
      closely as possible. These specific EEG parameters were actually calculated from
      periodograms obtained from the time series of EEG records of 14 patients with
      various neurological diseases. The automatic EEG interpretation system thus
      established was applied to the EEG data of these 14 subjects and to 3 additional
      EEGs, and the results were compared with those obtained through the visual
      interpretation by the EEGer. This automatic EEG interpretation was found to be in
      good agreement with the visual interpretation by the EEGer in most EEG records.
      In contrast with the previous automatic analyses of EEG which were focussed on
      certain aspects of EEG such as the dominant rhythm, the present system is unique
      in its capability of providing an integrative interpretation of the spontaneous
      awake EEG by taking into account all its features except for paroxysmal
      abnormalities.

PMID- 1375550
TI  - Influence of lateral gaze on electroencephalographic spectral power.
AB  - The effects of maintaining lateral gaze (as opposed to looking straight ahead) on
      electroencephalographic spectral power were tested in 12 right handed male
      subjects during eye opening (EO) and eye closure (EC). Our working hypothesis,
      based on Kinsbourne's paradigm, was that maintaining right lateral gaze activates
      the left hemisphere while maintaining left lateral gaze activates the right
      hemisphere, this activation resulting in a reduction in the spectral power over
      the hemisphere in question. Results showed that the variations in spectral power
      involved mainly the alpha frequency band. In the EC condition, the results were
      consistent with our working hypothesis: right lateral gaze produced a marked
      reduction in left hemispheric spectral power. In the EO condition, alpha power
      was constantly higher in the right hemisphere whether lateral gaze was maintained
      to the right or to the left. This can possibly be due to an attentional effect.
      Results are discussed with regard of the type of alpha rhythm and of the
      activation of cortical oculomotor centres. They shed light on the controversy
      concerning the existence of specific EEG correlates of cognitive activity, which
      preferentially involve each of the cerebral hemispheres.

PMID- 1375551
TI  - Electroencephalographic studies in workers exposed to solvents or pesticides.
AB  - The qEEG was studied in groups of young and old workers exposed to solvents
      (house and industrial painters) and in a group of workers exposed to pesticides.
      Three methods were used: a quantified visual scoring system, the neurometrics
      method and a multivariate analysis of mean frequencies. Using the visual
      assessment as well as the neurometrics method, the older painters showed more
      abnormalities than the younger painters and the pesticide exposed workers. The
      "profile" of abnormalities differed in all 3 groups. Changes of the mean spectral
      frequencies were mainly found in the subjects exposed to pesticides. In this
      study we concluded that the neurometrics method can be useful in
      neurotoxicological studies. With this technique minor changes in electrocortical
      function can be detected in seemingly normal workers. However, frequency
      parameters should be added to the power measures which are usually studied.

PMID- 1375552
TI  - Effect of the cholinesterase inhibiting substance galanthamine on human EEG and
      visual evoked potentials.
AB  - The action of galanthamine (GAL), a cholinesterase inhibiting substance, on
      resting EEG and on flash visual evoked potentials (VEPs) was tested in 9 healthy
      subjects. Alpha power was increased significantly in 4 of 8 subjects after the
      infusion of 10 mg, which provided a median inhibition of 47% of
      acetylcholinesterase in erythrocytes. Mean alpha frequency and peak alpha
      frequency decreased significantly in 5 of the 8 subjects by 0.22-0.98 Hz. Alpha
      power increase and alpha frequency decrease were not accompanied by changes in
      theta power. The amplitudes of the late components of the flash VEP were
      increased in 8 of 9 subjects receiving doses of 10-35 mg of GAL, while the early
      components remained unaffected. Increase of late VEP components was significantly
      correlated with the strength of cholinesterase inhibition. The synchronizing
      effect of GAL in these healthy volunteers obviously contrasts with the known
      desynchronizing effect of physostigmine in animal experiments.

PMID- 1375553
TI  - Low contrast stimuli enhance PERG sensitivity to the visual dysfunction in
      Parkinson's disease.
AB  - The pattern electroretinogram (PERG) was recorded at different contrast levels
      (96%, 71%, 47%) in 10 Parkinson's disease patients before and during dopaminergic
      monotherapy. The data were compared to a control group of 8 normal subjects
      recorded with the same procedure. PERG P50 latency progressively increased as
      contrast was decreased both in normal subjects and patients; however, this trend
      was much more pronounced in PD patients without therapy; consequently in this
      group the difference between P50 latency obtained with 96% and 47% contrast was
      statistically significant (P = 0.01, analysis of variance corrected by post-hoc
      Tukey test). By contrast this was not seen in the control group. Statistical
      analysis (Bonferroni's t test) showed at the 47% contrast level a significant P50
      latency increase (P less than 0.01) in PD patients without therapy if compared
      with the control group. Dopaminergic monotherapy induced a P50 latency recovery
      in PD patients. We conclude that low contrast stimuli enhance PERG sensitivity to
      the visual dysfunction of PD patients. Moreover, the effects observed after
      therapy confirm that abnormal contrast response functions in PD patients are
      linked to dopaminergic deficiency.

PMID- 1375554
TI  - Varying expressions of alerting mechanisms in wakefulness and across sleep
      states.
AB  - Alerting stimuli, such as intense tones, presented to cats in wakefulness (W)
      elicit the orienting response (OR) and/or the acoustic startle reflex (ASR) in
      conjunction with elicited ponto-geniculo-occipital waves (PGOE) from the lateral
      geniculate body (LGB) and elicited waves from the thalamic central lateral
      nucleus (CLE). Alerting stimuli presented during rapid eye movement sleep (REM)
      and non-rapid eye movement sleep (NREM) also elicit PGOE. We presented tones in
      W, REM and NREM to determine whether CLE could be obtained in sleep and to
      examine the patterns of responsiveness of PGOE and CLE across behavioral states.
      Also, we recorded ASR and OR and compared the response patterns of behavioral and
      central correlates of alerting. The subjects were 7 cats; all exhibited
      spontaneously occurring waves in LGB and CL. All cats exhibited PGOE and 5 cats
      exhibited CLE in W, REM and NREM. PGOE and CLE showed less evidence of
      habituation than did ASR and OR. The pattern of responsiveness of CLE across
      behavioral states was different from that found for PGOE, and spontaneous CL
      waves were much rarer than the LGB waves. ASR was elicited in 5 cats during W
      trials, and in 3 cats during REM trials. OR habituated rapidly in W and did not
      occur in REM and NREM. The data indicate that central mechanisms of alerting
      function in sleep states as well as in W and suggest that CLE and PGOE reflect
      activity in mechanisms underlying cortical desynchronization and visual processes
      which may act in concert during alerting.

PMID- 1375555
TI  - Frontal DC potentials in auditory selective attention.
AB  - Selective dichotic listening during periods of 35 sec was associated with
      negative shifts of the cortical DC potential. Amplitudes of negative DC
      potentials had maxima in frontal, in particular, in anterior frontal records. The
      temporal pattern of negative DC potentials was different between the fronto
      lateral records of the two hemispheres: in records from the right side, DC
      potentials declined during the 35 sec observation period, whereas they remained
      sustained in those of the left side. Different instructions ("attend left ear,"
      "attend right," "attend both") and different levels of pitch separation between
      deviants and standards had no effects on frontal negative DC potential shifts,
      which are discussed in terms of higher order control of selective dichotic
      listening.

PMID- 1375556
TI  - Relation of a negative ERP component to response inhibition in a Go/No-go task.
AB  - Previous studies have suggested that a negative component (N2) of the event
      related potential (ERP), whose peak latency is 200-300 msec after stimulus onset,
      may vary in amplitude depending on the neuronal activity required for response
      inhibition. To confirm this, ERPs were recorded in a Go/No-go paradigm in which
      subjects of one group (HI, n = 10) were asked to respond to Go stimuli with key
      pressing within a shorter period (less than 300 msec) than those of the other
      group (LI, n = 10) whose upper limit of the reaction time was relatively longer
      (less than 500 msec). All subjects had to withhold the Go response to the No-go
      stimuli without making overt muscle activities. The N2 component was recorded
      superposed on the initial descending limb of the P300 and other slow deflections,
      which were attenuated with a digital filter to measure the amplitude of N2. The
      N2 amplitude was significantly larger to the No-go stimulus than to the Go
      stimulus in both groups, but the N2 to the No-go stimulus was significantly
      larger in the HI group than in the LI group. These differences in N2 amplitude
      between conditions or groups were thought to be independent of other ERP
      components such as P300 and CNV. These results suggest that at least to some
      extent N2, which increased in amplitude when a greater effort was required to
      withhold the Go response, reflects the activity of a response inhibition system
      of the brain.

PMID- 1375557
TI  - Comparison of different staining methods for polyvinylidene difluoride membranes.
AB  - Several new staining methods for polyvinylidene difluoride membranes, including
      mercurochrome, silver and dimethylaminoazobenzene isothiocyanate staining were
      compared with Coomassie Brilliant Blue and gold staining. Of these, Coomassie was
      most versatile and completely compatible with ensuing microsequencing,
      immunostaining or other visualization methods, while gold and silver staining
      were more sensitive. Mercurochrome allows selective detection of sulfhydryl
      containing proteins while dimethylaminoazobenzene isothiocyanate staining may
      allow quantitation of sequenceable protein.

PMID- 1375558
TI  - Clinical, cytogenetic and immunological aspects in 4 cases resembling ataxia
      telangiectasia.
AB  - Four cases resembling ataxia telangiectasia, all characterized by the absence of
      telangiectasias, are presented. Two are sisters while the other 2 are sporadic
      cases. The 2 sisters, aged 14 and 12 years, present a progressive neurological
      disease similar to that characterizing the Louis-Bar syndrome. The clinical
      picture in 1 of the sporadic cases, a girl aged 13 years, differs from the
      typical ataxia telangiectasia in having bilateral pyramidal signs in the lower
      limbs. The last case, a girl aged 8 years, presents an atypical clinical pattern
      characterized by a severe mental retardation, quite modest cerebellar signs and
      absence of involuntary movements. The results of the immunological and
      cytogenetic investigations are presented and discussed.

PMID- 1375559
TI  - Partially reversible parkinsonism in Whipple's disease with antibiotherapy.
AB  - Progressive parkinsonism developed in a 68-year-old man who had Whipple's
      disease. Extrapyramidal disturbances improved dramatically after introduction of
      antibiotherapy (trimethoprim-sulfamethoxazole).

PMID- 1375560
TI  - Schistosoma mansoni: peritoneal plasmacytogenesis and polypoid transformation of
      mesenteric milky spots in infected mice.
AB  - We have studied inflammatory reactions in the mesenteric tissue of mice infected
      with Schistosoma mansoni. Perivascular tissue contained diffuse infiltrates of
      macrophages, eosinophilic granulocytes and lymphocytes. Angiogenesis in the
      perivascular adipose tissue was associated with superficial plasmacytogenic foci.
      Polypoid structures were occasionally formed adjacent to inflammatory foci in the
      adipose tissue, organized around loops of capillaries, with terminal formation of
      a glomerular capillary network embedded in connective tissue, covered by
      plasmacytes. We conclude that these structures are specialized milky spots
      dedicated to active plasmacytogenesis and antibody secretion into the peritoneal
      cavity of schistosome-infected mice.

PMID- 1375561
TI  - A protective monoclonal antibody with dual specificity for Plasmodium falciparum
      and Plasmodium berghei circumsporozoite proteins.
AB  - An IgM monoclonal antibody (Mab 36) which reacts with the circumsporozoite (CS)
      proteins of both P. falciparum and P. berghei was isolated from Plasmodium
      falciparum sporozoite-immunized mice. In assays of biological activity, Mab 36
      induces the CS precipitation reaction with live sporozoites and blocks the
      invasion of hepatoma cells by sporozoites in vitro at concentrations much lower
      than those observed for previously reported CS protein-specific monoclonal
      antibodies. Mab 36 also provided complete protection against P. berghei
      sporozoite challenge in mice at low doses. Linear epitope mapping revealed that
      the epitope specificities recognized by Mab 36 are completely encompassed by
      other monoclonals previously shown to be associated in vivo with protection
      against P. falciparum or P. berghei sporozoite infection. These results suggest
      that the ability to make high-affinity IgM antibody to specific CS protein repeat
      epitopes may be important for eliciting protection against malarial infection.

PMID- 1375562
TI  - Aprotinin: the ideal anti-coagulant?
AB  - The serine proteinase inhibitor, aprotinin, significantly reduces transfusion
      requirements during open heart surgery. Whether this benefit is associated with
      an increased tendency to thrombosis has not been studied. We investigated the
      effect of aprotinin in an experimental arterial thrombosis model. In 17 male
      Sprague-Dawley rats, the infrarenal aorta was replaced with 1.0-mm diameter PTFE
      grafts of varying lengths. The time to graft occlusion, recorded by palpation,
      Doppler ultrasound and a distal bleeding test, was 20.2 +/- 1.8 min, 35.8 +/- 6.1
      min and 43.7 +/- 6.6 min for grafts of 10, 7.5 and 5.0 mm respectively (r = 
      0.98, p less than 0.05). Following PTFE graft placement 24 Sprague-Dawley rats
      were given saline (n = 6), aprotinin (n = 6), heparin (n = 6), and heparin +
      aprotinin (n = 6). The time to occlusion was significantly prolonged in the
      aprotinin group (71.7 +/- 20.4 min vs. 20.2 +/- 1.8 min, p less than 0.05). The
      time to thrombosis for heparin + aprotinin and heparin alone was also
      significantly prolonged (p less than 0.05). Prothrombin times (PT) were 21.9 +/-
      3.0 s for control, 29.4 +/- 6.2 s for aprotinin, 40.7 +/- 2.5 s for heparin and
      39.9 +/- 14.5 s for heparin + aprotinin (p less than 0.05 vs. control for all
      values). Bleeding time was not prolonged with aprotinin (3.0 +/- 0.9 min vs. 2.9
      +/- 0.7 min). The bleeding time was 18.9 +/- 4.1 min for heparin + aprotinin and
      22.5 +/- 2.3 min for heparin alone (p less than 0.05 vs. control for both
      values).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375563
TI  - Characterization of the RNA processing enzyme RNase III from wild type and
      overexpressing Escherichia coli cells in processing natural RNA substrates.
AB  - 1. A precursor to small stable RNA, 10Sa RNA, accumulates in large amounts in a
      temperature sensitive RNase E mutant at non-permissive temperatures, and somewhat
      in an rnc (RNase III-) mutant, but not in an RNase P- mutant (rnp) or wild type
      E. coli cells. 2. Since p10Sa RNA was not processed by purified RNase E and III
      in customary assay conditions, we purified p10Sa RNA processing activity about
      700-fold from wild type E. coli cells. 3. Processing of p10Sa RNA by this enzyme
      shows an absolute requirement for a divalent cation with a strong preference for
      Mn2+ over Mg2+. Other divalent cations could not replace Mn2+. 4. Monovalent
      cations (NH+4, Na+, K+) at a concentration of 20 mM stimulated the processing of
      p10Sa RNA and a temperature of 37 degrees C and pH range of 6.8-8.2 were found to
      be optimal. 5. The enzyme retained half of its p10Sa RNA processing activity
      after 30 min incubation at 50 degrees C. 6. Further characterization of this
      activity indicated that it is RNase III. 7. To further confirm that the p10Sa RNA
      processing activity is RNase III, we overexpressed the RNase III gene in an E.
      coli cells that lacks RNase III activity (rnc mutant) and RNase III was purified
      using one affinity column, agarose.poly(I).poly(C). 8. This RNase III preparation
      processed p10Sa RNA in a similar way as observed using the p10Sa RNA processing
      activity purified from wild type E. coli cells, confirming that the first step of
      p10Sa RNA processing is carried out by RNase III.

PMID- 1375564
TI  - Methotrexate local injection for unruptured tubal pregnancy: an alternative to
      laparotomy?
AB  - Fifty-nine women with early unruptured tubal pregnancy were treated by a single
      local injection of methotrexate at laparoscopy. All 59 patients underwent the
      procedure without any adverse reaction, 47 (80%) of them needing no laparotomy.
      Twelve patients required a laparotomy for reasons such as rising beta-hCG levels
      and abdominal pain with or without rising levels of beta-hCG. Only one patient
      ruptured the tube. None of the women needed a blood transfusion. We found tubal
      patency in 19 out of 21 patients at follow up hysterosalpingography. Eleven
      pregnancies were subsequently reported, one of them tubal. The appearance of the
      injected tube was absolutely normal in three patients, one at cesarean section
      and two at repeated laparoscopy. No peritubal adhesions were observed. We suggest
      that this new technique is a safe and effective alternative to laparotomy in a
      patient with an early unruptured tubal pregnancy.

PMID- 1375565
TI  - Development of cycles for lyophilization.
AB  - In order to find the freeze-drying cycle for the effective drying of a given
      biological entity or a material of biologic origin by sublimation of ice in
      vacuo, numerous time-consuming, trial and error preliminary studies have been
      required. Following a series of studies using different shelf temperatures, -30
      degrees, -10 degrees, 0 degrees, +10 degrees and +20 degrees C, and elapsed times
      of 1,500, 2,000, 2,700, 4,000 and 5,500 minutes, plug characteristics and
      contents of residual moistures of freeze-dried 3 ml samples of 2% serum albumin
      were determined. Using the statistical method of least squares, geometric curves
      were fitted to the plot of times versus residual moistures for the several shelf
      temperatures. The equations for the fitted curves were used to construct a table
      showing the contents of residual moistures at 300 minute intervals. This table
      was used for developing successful drying cycles for several concentrations of
      serum albumin, dilute solutions of interferon, and serum containing HLA
      antibodies.

PMID- 1375566
TI  - Minor neurological dysfunction from birth to 12 years. I: Increase during late
      school-age.
AB  - To study the hypothesis that the frequency of minor neurological dysfunction
      (MND) stabilizes around the age of nine years, two groups of the Groningen
      Perinatal Project (GPP) were re-examined at 12 years. The study group (N = 174)
      was selected on the basis of the presence of MND at nine years; the control group
      comprised 172 neurologically normal children. The hypothesis was rejected:
      extrapolation of the findings to the total GPP population showed that the over
      all rate of MND increased. Control children who developed MND were mainly boys
      who had been neurologically abnormal at birth or were born preterm and/or had
      experienced an adversity in combination with asphyxia. Interval complications
      between nine and 12 years were related to the emergence of MND.

PMID- 1375567
TI  - Minor neurological dysfunction from birth to 12 years. II: Puberty is related to
      decreased dysfunction.
AB  - To determine whether puberty is related to decreased minor neurological
      dysfunction (MND), 174 children from the Groningen Perinatal Project who had had
      MND at nine years were re-examined at 12 years. No signs of MND could be
      demonstrated in 39 of the children, 33 of whom showed at least three signs of
      puberty. The presence of minor physical anomalies was associated with persisting
      MND. The authors hypothesise that puberty is related to a decrease in MND, and
      discuss the role of hormonal changes in relation to the decrease in minor signs.
      Re-examination at 14 years will be necessary to confirm this hypothesis, since 68
      per cent of the children had not yet reached puberty. Children with MND reached
      puberty no later than those without.

PMID- 1375568
TI  - Phosphorylation of ligand-gated ion channels: a possible mode of synaptic
      plasticity.
AB  - Most neurotransmitter receptors examined to date have been shown either to be
      regulated by protein phosphorylation or to contain consensus sequences for
      phosphorylation by protein kinases. Neurotransmitter receptors that mediate rapid
      synaptic transmission in the nervous system are the ligand-gated ion channels and
      include the nicotinic acetylcholine receptors of muscle and nerve and the
      excitatory and inhibitory amino acid receptors: the glutamate, GABAA, and glycine
      receptors. These receptors are multimeric proteins composed of homologous
      subunits which each span the membrane several times and contain a large
      intracellular loop that is a mosaic of consensus sites for protein
      phosphorylation. Recent evidence has suggested that extracellular signals
      released from the presynaptic neuron, such as neurotransmitters and neuropeptides
      as well as an extracellular matrix protein, regulate the phosphorylation of
      ligand-gated ion channels. The functional effects of phosphorylation are varied
      and include the regulation of receptor desensitization rate, subunit assembly,
      and receptor aggregation at the synapse. These results suggest that
      phosphorylation of neurotransmitter receptors represents a major mechanism in the
      regulation of their function and may play an important role in synaptic
      plasticity.

PMID- 1375569
TI  - Connections: heart disease, cellular electrophysiology, and ion channels.
AB  - Our purpose in this article is to examine the hypothesis that both myocardial
      disease and ischemia can alter the electrophysiologic function of the ion
      channels responsible for the cellular electrical activity of the heart. Changes
      in the intracellular and extracellular milieus occur during ischemia and can
      alter the electrophysiology of several species of ionic channels and the cellular
      electrophysiologic activity of cardiac myocytes. Included are 1) changes in
      extracellular [K+] and pH and in intracellular [Na+], [Ca2+], and pH; 2)
      accumulation of noxious metabolic products such as lysophosphatidylcholine; and
      3) depletion of intracellular ATP. Finally, ischemia or disease (e.g.,
      hypertrophy) can alter the electrophysiology of at least two types of K+
      channels, the A-like channels underlying the transient outward current and the
      inward rectifier, by mechanisms that apparently do not involve alteration of
      either the intra- or extracellular milieus. Findings suggest that the expression
      of cardiac A-like channel function can be altered by hypertrophy and that at
      least one intrinsic conductance property of the inward rectifier can be altered
      by ischemia. We speculate that the control of expression, function, and
      regulation of cardiac ion channels can be affected at the molecular level by
      heart disease and myocardial ischemia.

PMID- 1375570
TI  - Secretagogue-evoked time-course changes on pancreatic juice secretion in the
      anaesthetized rat.
AB  - 1. In the present time-course study, we have examined the interactions between
      the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and the synthetic
      gut hormones, cholecystokinin-octapeptide (CCK-8) and secretin on pancreatic
      juice secretion in anaesthetized rat. 2. Administration of either TPA (10(-8) mol
      kg-1 hr-1), secretin (100 pmol kg-1 hr-1) or CCK-8 (150 pmol kg-1 hr-1) in the
      anaesthetized rat resulted in marked time-course increases in pancreatic juice
      flow, amylase secretion and total protein output compared to saline controls. The
      effect of secretin on juice flow was more pronounced and sustained compared to
      the smaller responses obtained with either CCK-8 or TPA. Similarly, CCK-8 evoked
      increases in protein output and amylase secretion compared to the responses
      obtained with either secretin or TPA. 3. Simultaneous infusion of TPA with either
      CCK-8 or secretin resulted in a marked reduction in pancreatic juice flow, total
      protein output and amylase secretion compared to the responses obtained with
      either CCK-8 or secretin alone. 4. Administration of polymyxin B (10(-8) mol kg-1
      hr-1), a protein kinase C inhibitor with either TPA and CCK-8 or TPA and secretin
      caused a partial reduction of the inhibitory effect of TPA on CCK-8 and secretin
      evoked secretory responses. 5. The present study further implicates the
      involvement of protein kinase C in the modulation of CCK-8 and secretin-induced
      pancreatic juice secretion in the anaesthetized rat.

PMID- 1375571
TI  - Effective portal insulin delivery with enzyme-protected capsules in
      pancreatectomized pigs.
AB  - 1. Plasma concentrations of insulin, C-peptide, glucagon and glucose were
      measured in surgically pancreatectomized pigs given insulin into the colon
      directly and in enteric peptidase-resistant (methacrylic acid copolymer
      encapsulated) form. 2. Following introduction of insulin-containing capsules,
      plasma insulin concentration rose from 2.7 +/- 0.1 microU/ml to 110.9 +/- 51.9
      microU/ml in the portal vein, and from 2.6 +/- 0.1 microU/ml to 26.9 +/- 7.3
      microU/ml in the systemic circulation. Corresponding portal and systemic values
      after direct (non-encapsulated) insulin instillation were 28.2 +/- 15.9 microU/ml
      to 44.8 +/- 13.0 microU/ml and 7.5 +/- 2.6 microU/ml to 15.2 +/- 2.5 microU/ml
      respectively. Insulin concentrations peaked at 75 min in the group as a whole and
      between 60-90 min in individual animals. Absorption was most pronounced in pigs
      given aprotinin (a trypsin inhibitor) with insulin. 3. Plasma portal vein glucose
      concentrations fell from 76.2 +/- 8.9 mg/dl to 31.1 +/- 3.2 mg/dl 150 min after
      encapsulated insulin administration. Corresponding systemic glucose levels were
      84.5 +/- 11.0 mg/dl and 37.0 +/- 1.4 mg/dl. 4. Colonic administration of insulin
      in methacrylic acid coated capsules results in peak portal and systemic insulin
      levels 60-90 min after administration. Co-administration of aprotinin enhances
      the fraction of insulin absorbed.

PMID- 1375572
TI  - Effects of some calcium antagonists upon the activity of common antiepileptic
      compounds on sound-induced seizures in DBA/2 mice.
AB  - 1. Flunarizine (2.65 mumol/kg, i.p.) and nimodipine (5.25 mumol/kg, i.p.)
      potentiated the anticonvulsant properties of phenytoin, phenobarbital and
      valproate against audiogenic seizures in DBA/2 mice. 2. Diltiazem (5.25 mumol/kg,
      i.p.) was able to potentiate the antiseizure activity of phenytoin but was not
      effective against the anticonvulsant action of phenobarbital and valproate. 3.
      Verapamil (5.25 mumol/kg, i.p.) was unable to potentiate the anticonvulsant
      properties of all antiepileptic drugs studied. 4. Bay K 8644 (1,4-dihydro-2,6
      dimethyl-3-nitro-4-(2-trifluorophenyl)-pyridine- 5-carboxylic acid), a calcium
      agonist at a dose of 2.65 mumol/kg, i.p., induced a reduction of anticonvulsant
      potency of phenytoin, phenobarbital and valproate. 5. None of the calcium
      antagonists used significantly increased the plasma levels of antiepileptic
      compounds or significantly affected the body temperature changes induced by
      anticonvulsant drugs. 6. It may be concluded that some calcium antagonists
      enhance the anticonvulsant properties of some antiepileptic drugs against
      audiogenic seizures. A pharmacokinetic interaction does not seem responsible for
      these effects.

PMID- 1375573
TI  - Molecular analysis of the zeste-white interaction reveals a promoter-proximal
      element essential for distant enhancer-promoter communication.
AB  - We have analyzed the eye and testis enhancers located 1 kb upstream of the
      transcription start site of the white gene. Both enhancers confer the
      corresponding tissue-specific expression on a heterologous promoter as well as on
      the white promoter. The eye determinant consists of multiple elements, each able
      to stimulate eye-specific expression. It also contains five binding sites for the
      zeste protein while the immediately adjacent testis element contains none. Site
      directed mutation of these zeste binding sites abolishes the zeste-white
      interaction but does not significantly affect the eye enhancer activity,
      indicating that they are not important for the eye enhancer activity per se.
      Other zeste binding sites just upstream of the promoter are not necessary for the
      zeste-white interaction. We conclude that the overlap of the eye enhancer with
      the zeste binding sites is responsible for the zeste-white interaction and
      explains why this interaction affects eye but not testis expression. Sequence
      deletion or substitution experiments suggested that the white promoter is
      internal to the transcription start site; the zeste protein is not required for
      distant enhancer action but a 95-bp promoter-proximal sequence is essential for
      distant enhancer-promoter interaction. This element may serve as an anchor to
      stabilize formation of a loop that brings the enhancer to the vicinity of the
      promoter.

PMID- 1375574
TI  - Pathophysiology and management of phantom limb pain.
AB  - Phantom pain phenomenon is a poorly understood but relatively common sequela of
      limb amputation that may result in significant psychological and physical
      morbidity. In this review, proposed pathoneurophysiological mechanisms for the
      development of phantom pain are reviewed as well as psychological mechanisms that
      may be involved. The authors recommend an integrated approach to management of
      chronic phantom pain that takes into consideration the multiple factors that may
      contribute to its etiology.

PMID- 1375575
TI  - Immunobiochemical assay for determination of nuclear steroid receptors.
AB  - Knowledge of receptor status is important for therapeutic strategies in hormone
      dependent tumors. Therefore, methods specifically predicting biological response
      to endocrine therapy are essential. We investigated the receptor modulation of
      two breast tumors and one endometrial tumor in the nude mice model after
      injection of 20 micrograms 17 beta-estradiol. To differentiate the unoccupied and
      the occupied receptor sites, we used the enzyme immunoassay (EIA) for estrogen
      receptors (ER) under low- and high-salt conditions. With low-salt extraction we
      found a sharp decrease of the ER-EIA values within the first hour after estradiol
      treatment. This decrease continued for 24 hr until recovery to pretreatment
      levels occurred. In contrast, the ligand-receptor complexes tightly bound to
      acceptor sites on the DNA increased more than three times within 1 hr. These high
      levels could be measured for almost 12 hr, and then pretreatment levels were
      reestablished. The PgR-EIA values under low-salt conditions increased 10-fold
      within 12 hr, indicating an intact receptor mechanism. We conclude that this
      immunobiochemical method is a useful tool in determining receptor sites: those
      both unbound and those tightly bound to nuclear acceptors.

PMID- 1375576
TI  - Malignant ovarian germ cell tumors: the experience at the Hospital de la Santa
      Creu i Sant Pau.
AB  - From 1979 to 1990, 33 patients with pathologically confirmed malignant ovarian
      germ cell tumors (MOGCT) were referred after initial surgical procedure at the
      Department of Oncology, Hospital de la Santa Creu i Sant Pau. The median age was
      22 years (range, 10 to 39). Stage distribution was as follows: stage I, 12
      patients; stage II, 6 patients; stage III, 11 patients; stage IV, 3 patients; and
      unstaged, 1 patient. The histologic diagnoses were 10 dysgerminomas, 4 endodermal
      sinus tumors, 11 immature teratomas, and 8 mixed germ cell tumors. Twenty-eight
      out of the thirty-three patients received postoperative chemotherapy with POMB
      ACE-PAV or other platinum-containing regimens. One patient with stage IV disease
      failed to respond to chemotherapy and she died. Sixteen out of the twenty-eight
      treated patients had second-look laparotomy, which showed mature teratoma in six
      and persistent malignant teratoma in one patient. This last patient had complete
      remission with second regimen. No patient has developed recurrence. With a median
      follow-up of 66 months (range, 10 to 133), 32 patients (97%) are alive without
      evidence of disease. These data confirm that platinum-containing regimens have
      dramatically improved the prognosis for patients with MOGCT. This paper discusses
      primary chemotherapy and the role of the second-look in these patients.

PMID- 1375577
TI  - [Expression and function of glycine-gated Cl- channels].
AB  - Glycine is a major inhibitory neurotransmitter in the spinal cord and brain stem.
      Glycine acts by increasing the Cl- permeability through activation of a specific
      receptor/ion channel complex consisting of a pentameric subunit assembly.
      Molecular cloning has disclosed the nature of receptor subunits alpha and beta.
      While the role of the beta subunit is still unclear, the alpha subunit functions
      in both ligand (agonist/antagonist) binding and ion channel formation. It has
      been demonstrated that there are two isoforms of the alpha subunit, alpha 1 and
      alpha 2. The mRNAs encoding these subunit isomers are transcribed from different
      genes, in spite of their structural similarity. The alpha 1 mRNA is abundant in
      adult spinal cord, whereas the alpha 2 mRNA is mainly expressed in developing
      spinal cord as well as various regions of brain tissue. The single channel
      properties were examined in outside-out patches excised from Xenopus oocyte
      membrane expressing alpha 1 or alpha 2 homomeric receptors. The mean open time of
      alpha 2 channels was 70-times longer than that of alpha 1 channels. The subunit
      switching from alpha 2 to alpha 1, and resulting shortening of channel kinetics,
      may ensure a rapid motor control in adult animals.

PMID- 1375579
TI  - Immunolocalization, quantitation and cellular heterogeneity of apolipoprotein B
      in rat hepatocytes.
AB  - Hepatocyte autofluorescence represents a major problem in immunofluorescence
      studies with fluorescein conjugates because of significant spectral overlap. We
      describe a method for immunostaining hepatocytes with R-phycoerythrin (a
      fluorochrome with minimal overlap with autofluorescence) with paraformaldehyde
      fixation and Triton X-100 permeabilization for better antibody penetration. This
      method produced both perinuclear (presumed Golgi apparatus) and dispersed,
      reticular staining (presumed endoplasmic reticulum) in rat hepatocytes in culture
      stained with a monoclonal antibody to rat apolipoprotein B. Treatment with
      brefeldin A resulted in loss of apolipoprotein B perinuclear staining and
      increased reticular immunofluorescence consistent with known properties of
      brefeldin A (inhibition of protein transport within the secretory pathway by
      dissolution of Golgi bodies). This suggests that apolipoprotein B epitopes are
      present in both Golgi bodies and endoplasmic reticulum. To demonstrate the
      utility of the technique for quantitative studies, static cell cytofluorometry of
      brefeldin A-treated cells was performed, demonstrating increases in specific
      immunofluorescence of apolipoprotein B corresponding closely to results estimated
      by monoclonal antibody radioimmunoassays of cellular homogenates. The technique
      was then used with flow cytometry of single-cell suspensions of control rat
      hepatocytes derived from immunostained primary cultures to reveal cell-to-cell
      heterogeneity of apolipoprotein B epitope expression manifested as apolipoprotein
      B-negative and positive populations. Results for brefeldin A-treated cells
      revealed even clearer delineation of heterogeneity as indicated by frank
      bimodality of the populations, along with not only higher mean apolipoprotein B
      levels but also a significantly higher proportion of apolipoprotein B-positive
      cells than in the control.

PMID- 1375578
TI  - Inhibition of superoxide and nitric oxide release and protection from
      reoxygenation injury by Ebselen in rat Kupffer cells.
AB  - Luminol chemiluminescence in phorbolester-activated cultured rat liver Kupffer
      cells was strongly inhibited by the selenoorganic compound ebselen (IC50 = 2
      mumol/L). Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]one) also diminished
      reduction of ferricytochrome c (IC50 = 10 mumol/L), indicating a suppression of
      superoxide anion formation. Likewise, in lipopolysaccharide-pretreated Kupffer
      cells, ebselen proved to be a potent inhibitor of the conversion of oxyhemoglobin
      to methemoglobin (IC50 = 3 mumol/L) as a measure of nitric oxide formation. The
      sulfur-containing analog (2-phenyl-1,2-benzisothiazol-3[2H]one) and the ebselen
      derivative, methylselenobenzanilide, were inactive. These results indicate that
      ebselen is a potent inhibitor of NADPH oxidase in Kupffer cells, as has been
      reported for other macrophages and granulocytes. In addition, they suggest a
      novel characteristic of ebselen, namely very effective inhibition of nitric oxide
      synthase of macrophages. In line with its inhibitory effects on the release of
      reactive oxygen species by macrophages, complemented by its antioxidant
      properties, ebselen was potent in the prevention of reoxygenation injury of
      Kupffer cells (IC50 approximately 5 mumol/L).

PMID- 1375580
TI  - Effects of partial hepatectomy on hepatic insulinlike growth factor binding
      protein-1 expression.
AB  - Insulinlike growth factor binding proteins modulate the action of the insulinlike
      growth factors in various bioassays and may regulate the bioavailability of the
      insulinlike growth factors in vivo. Because the insulinlike growth factors may
      influence hepatic regeneration, we have examined the effect of partial
      hepatectomy on serum insulinlike growth factor binding proteins and on the
      abundance of insulinlike growth factor binding protein-1 messenger RNA in the
      liver. All rats were fasted before and after partial hepatectomy or sham
      operation to avoid the confounding effects of difference in food intake. Using a
      conventional protocol, 70% of the liver was removed, and groups of four or five
      rats were killed at different intervals after partial hepatectomy. Sham-operated
      rats served as controls. Pooled sera from each group of rats were analyzed by
      ligand blotting with 125I-insulinlike growth factor-I. Liver RNA from individual
      rats was analyzed by slot-blot and Northern-blot hybridization. A small decrease
      in the 39- to 42-kD insulinlike growth factor binding protein was apparent in
      sera from both the sham-operated and partial hepatectomized rats. In contrast, a
      dramatic increase (fivefold) in the 29-kD serum insulinlike growth factor binding
      protein (insulinlike growth factor binding protein-1) was apparent only in the
      partial hepatectomized rats. Hepatic insulinlike growth factor binding protein-1
      messenger RNA abundance was significantly increased (1.99 +/- 0.18-fold; p less
      than 0.05) at 1 hr, reached a peak of 2.32 +/- 0.22-fold (p less than 0.01) at 3
      hr after partial hepatectomy and returned to basal levels over the subsequent 6
      to 12 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375581
TI  - Cytokeratin polypeptide in gastrointestinal adenocarcinomas displaying squamous
      differentiation.
AB  - In the present study we investigated the cytokeratin (CK) polypeptide expression
      in gastric and colonic adenocarcinomas. A battery of monoclonal anti-cytokeratin
      specific antibodies and anti-vimentin were used. While the majority of cases
      displayed simple epithelial characteristics, in three of 17 cases of gastric
      adenocarcinomas and in one of 20 cases of colonic adenocarcinomas, CK
      polypeptides 13 (54 kd) and 16 (48 kd) were occasionally detected. These CK
      polypeptides, characteristic of squamous nonkeratinizing epithelia, were found in
      cases in which no evidence of squamous differentiation could be demonstrated by
      histologic examination. We believe that the presence of these unique CK
      polypeptides points to the squamous differentiation potential of the tumor cells.

PMID- 1375582
TI  - Determinant analysis and interaction studies on monoclonal antibodies to bovine
      IgG1 and IgG2.
AB  - Two mouse monoclonal antibodies SKb1 and SKb6 were prepared by fusion of myeloma
      cells with spleen cells of female Balb/c mouse immunized with a mixture of bovine
      IgG1 and IgG2. In radioimmunoassay, SKb1 bound specifically to IgG2 but SKb6
      reacted with both IgG1 and IgG2 molecules. In the competition experiments, heavy
      chain isolated from bovine IgG could inhibit the binding of 125I-IgG1 and 125I
      IgG2 to SKb6, while it failed to inhibit the binding of 125I-IgG2 to SKb1. The
      epitope reacting with SKb1 was found to be present not only on bovine IgG2 but
      also on goat IgG and was not present on IgG molecules isolated from the serum of
      rabbit, rat, sheep, horse, human and monkey. Similarly, the epitope reacting to
      SKb6 was found to be present on bovine IgG1 and IgG2 and also on IgG molecules
      isolated from goat and sheep serum but was absent in the IgG molecules isolated
      from the serum of rabbit, rat, horse, human and monkey. The association constants
      of the interactions of SKb1 with 125I-IgG2 and of SKb6 with 125I-IgG1 and 125I
      IgG2, determined by Scatchard analysis, Steward-Petty plot and Sips plot, were
      found to be in the order of 10(8)-10(10) L/M. The association constants were
      determined at varying temperatures to obtain the thermodynamic parameters. The
      enthalpy (delta H0) and entropy (delta S0) values for the above antigen-antibody
      interactions were in the range of 9.15-15.96 kcal/mole and 36.96-41.15 eu/mole
      respectively. The heterogeneity indices for similar interactions determined by
      Sips equation were consistent with the expected values for binding of monoclonal
      antibodies with homogeneous protein determinants.

PMID- 1375583
TI  - Parasite-specific T-cell responses of trypanotolerant and trypanosusceptible
      cattle during infection with Trypanosoma congolense.
AB  - During primary tsetse-transmitted challenge of Boran (Bos indicus) cattle with
      Trypanosoma congolense ILNat 3.1, a transient parasite antigen-specific T-cell
      proliferative response was observed in peripheral blood mononuclear cells and
      splenic mononuclear cells stimulated in vitro. A response was also observed with
      cells of N'Dama (Bos taurus) cattle, but in this case higher stimulation indices
      were observed and the response was maintained until the termination of the
      experiment at 40 days post-infection (p.i.). The highest parasite antigen
      specific proliferative responses were observed at 20 days post-infection. At this
      time N'Dama cattle not only responded to the antigens derived from the infecting
      clone (ILNat 3.1), but also to antigens from a clone of a different serodeme
      (ILNaR 2), whereas Boran cattle only recognized antigens from the infecting clone
      of parasites. To determine the molecular mass of the antigenic trypanosome
      proteins, whole trypanosome lysates made from T. congolense ILNat 3.1 were
      fractionated by SDS-PAGE and transferred onto nitrocellulose membranes. The major
      protein bands were isolated and used directly in T-cell proliferation assays. In
      this instance, no differences in the antigen recognition profiles of Boran and
      N'Dama cattle were observed. The variable surface glycoprotein did not induce T
      cell proliferation in infected cattle despite the presence of serum antibodies to
      this variable antigenic type.

PMID- 1375585
TI  - Asymmetric non-precipitating antibodies in commercial hyperimmune gamma-globulin
      for therapeutic use.
AB  - The presence of asymmetric (non-precipitating or co-precipitating) antibodies has
      been studied in three commercial preparations of antitetanus gamma-globulin. It
      was found that 27% of the specific antibodies are of asymmetric type, a value two
      to three times higher than that found in normal IgG. In toxicity tests in mice
      with tetanus toxin, the asymmetric antibodies were 2.7 times less effective than
      the symmetric ones. It is concluded that the protection capacity of the tetanus
      gamma-globulin preparations is dependent on the ratio of symmetric to asymmetric
      antibodies. The high content of asymmetric antibodies is probably due to the fact
      that immunization is performed with the antigen in a particulate form.

PMID- 1375584
TI  - Immunization of guinea-pigs and cattle against adult Rhipicephalus appendiculatus
      ticks using semipurified nymphal homogenates and adult gut homogenate.
AB  - Guinea-pigs inoculated with crude homogenate of unfed nymphs of the tick
      Rhipicephalus appendiculatus and with three semipurified fractions of the
      homogenate obtained by gel permeation chromatography, acquired a significant
      degree of immunity to infestation with adults of this tick. Fraction 2 induced
      the highest reduction (66%) in mean weight of engorged females followed by crude
      homogenate and fractions 1 and 3. Calves immunized with crude homogenates of
      unfed nymphs, fraction 2 of nymphal homogenate, and gut homogenate of unfed
      females also acquired immunity against adults of R. appendiculatus. The mean
      weight of engorged females fed on calves inoculated with nymphal fraction 2 was
      the lowest of all five groups of calves on which females fed. The reduction in
      weight (38%) was not significantly different from that observed for females fed
      on calves inoculated with crude nymphal homogenate (31%) or females from third
      infestation of adult ticks. No differences in the weight and hatchability of egg
      batches produced by engorged females collected from the five groups of calves
      were observed. Analysis of sera collected from the five groups of calves showed
      that the concentration of albumin, alpha-1, alpha-2 and beta-globulins fluctuated
      and no significant differences between the treated groups were observed. The
      levels of gamma-globulin increased in treated groups including the group
      inoculated with adjuvant only, but unlike previous reports no increase in gamma
      globulin or a correlation between the level of gamma-globulin and the degree of
      resistance acquired were observed in calves exposed to repeated tick
      infestations. However, the increase in the concentration of gamma-globulin in
      calves inoculated with fraction 2 or crude nymphal homogenate was higher than
      that observed in the other groups.

PMID- 1375586
TI  - Calcitonin gene-related peptide in noradrenergic transmission in rat
      hypothalamus.
AB  - In the present study, we examined the regulatory mechanisms of calcitonin gene
      related peptide on norepinephrine release in rat hypothalamus. Calcitonin gene
      related peptide inhibited the stimulation-evoked norepinephrine release from
      hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner, although
      the peptide did not affect basal release of norepinephrine. The blockade of the
      alpha 2-adrenergic receptors by RX 781094 failed to modulate the inhibitory
      effects of calcitonin gene-related peptide on norepinephrine release.
      Pretreatment of slices with islet activating protein, a toxin that interferes
      with the coupling of the inhibitory receptors to adenylate cyclase, did not
      affect the suppression of norepinephrine release by calcitonin gene-related
      peptide. However, Bay K 8644, a dihydropyridine-sensitive calcium channel
      agonist, significantly reversed the inhibitory effects of calcitonin gene-related
      peptide on norepinephrine release. These results show that calcitonin gene
      related peptide might inhibit norepinephrine release in rat hypothalamus,
      partially mediated by interactions with dihydropyridine-sensitive Ca2+ channels
      but not by interactions with presynaptic alpha 2-adrenergic receptors and
      inhibitory guanosine triphosphate binding proteins. Furthermore, the finding
      suggests the possible involvement of calcitonin gene-related peptide in the
      regulation of sympathetic nervous activity in the central nervous system.

PMID- 1375587
TI  - Ganglionic blockade with tetraethylammonium in conscious rats.
AB  - The sympathetic ganglionic blocking agent tetraethylammonium has been used as a
      clearance marker for the measurement of renal plasma flow, but the sympathetic
      ganglionic blocking dose in rats is unknown. In light of differential reflex
      activation of sympathetic nerve activity to heart and kidney, we compared the
      effect of tetraethylammonium on renal nerve activity, mean arterial pressure, and
      heart rate. Conscious rats were infused with either vehicle (isotonic saline) or
      tetraethylammonium (n = 7 in both groups). Tetraethylammonium was infused
      cumulatively (35 minutes per dose) in the following doses: 10(-5), 10(-4), 10(
      3), 10(-2), and 10(-1) g/kg body wt per hour. Doses for 15% reduction were 10(-1)
      for mean arterial pressure, 0.55 x 10(-1) for heart rate, and 0.055 x 10(-1) g/kg
      body wt per hour for renal nerve activity. Renal nerve activity was abolished at
      10(-1) g/kg body wt per hour; mean arterial pressure and heart rate were
      unchanged at doses lower than 10(-1) g/kg body wt per hour. The lethal dose was 1
      g/kg body wt per hour. No changes were observed in vehicle-treated animals.
      Tetraethylammonium at 10(-1) g/kg body wt per hour resulted in an attenuated
      increase in renal nerve activity during acetylcholine-induced reduction in mean
      arterial pressure, reflecting arterial baroreceptor inhibition. We conclude that
      renal nerve activity is 10- and 18-fold more sensitive to sympathetic ganglionic
      blockade than heart rate and mean arterial pressure, respectively. When
      tetraethylammonium is used as a clearance marker for measurement of renal plasma
      flow in rats, it should be administered in doses less than 10(-2) g/kg body wt
      per hour.

PMID- 1375588
TI  - Expression and different polarity of aminopeptidase N in normal human colonic
      mucosa and colonic tumors.
AB  - Expression and cellular localization of brush-border enzymes (aminopeptidase N,
      dipeptidylpeptidase IV, lactase, maltase) in normal human colon, colonic polyps
      and malignant intestinal tumors were investigated with a panel of monoclonal
      antibodies reacting with either native or denatured proteins. The enzymes were
      detected on cryostat sections by indirect immunofluorescence staining, or
      affinity-purified and analyzed by gel electrophoresis and immunoblotting.
      Dipeptidylpeptidase IV, lactase and maltase were absent from all samples
      examined, while aminopeptidase N (APN) was detected at the basal membrane of the
      epithelial cells in most specimens of colon obtained from individuals free of
      intestinal tumors. In contrast, APN was frequently localized at the luminal
      membrane of the surface epithelium in large-intestinal mucosa distal to tumors,
      adenomas and hyperplastic polyps, and from members of hereditary colon cancer
      syndrome families. APN was also expressed in colonic tumors, where it was present
      in an apical cell membrane location in 3/23 adenomas and 14/35 adenocarcinomas
      examined. No correlation was found between tumor-cell invasiveness (classified by
      "Dukes" stage) and expression or cellular location of aminopeptidase N.
      Histologically, all positive tumors were moderately or well differentiated. These
      results suggest that aminopeptidase N is normally expressed in adult human colon,
      but epithelial cells in the large and small intestine differ in their ways of
      sorting this enzyme intracellularly and eventually inserting it into different
      aspects of their surface membrane, a process which may be altered at an early
      stage of carcinogenesis.

PMID- 1375589
TI  - Increased expression of alpha IIb beta 3 integrin in subpopulations of murine
      melanoma cells with high lung-colonizing ability.
AB  - Four subpopulations of B16 amelanotic melanoma cells, possessing different
      abilities to induce platelet aggregation (TCIPA) and to form lung colonies, were
      isolated by centrifugal elutriation. The expression of alpha IIb beta 3, alpha v
      beta 3 and alpha 5 beta 1 integrins was examined in the 4 subpopulations in order
      to determine the relationship between integrin receptor expression and tumor-cell
      metastatic potential. The mRNA of alpha IIb, alpha 5, beta 1 and beta 3 was
      detectable in the 4 subpopulations by Northern blotting. A gradual increase in
      mRNAs and cell-surface immunoreactivity of the alpha IIb beta 3 receptor, but not
      in their gene copies, was observed from the low to the high metastatic
      subpopulations. The ability of tumor cells to adhere to fibronectin and
      subendothelial matrix (SEM) increased in parallel. In the high metastatic cells,
      the alpha IIb beta 3 receptors, but not the alpha 5 beta 1 receptors, were
      localized to focal adhesion plaques. Incubation of the high metastatic cells with
      alpha IIb beta 3-specific antibodies reduced their matrix adhesion, TCIPA and
      lung-colonizing abilities. In contrast, in the low met- astatic cells, SEM
      adhesion and lung-colony formation were not affected by anti-alpha IIb beta 3
      antibody treatment. Incubation of either the low or the high metastatic
      subpopulation with an alpha 5 beta 1-specific antibody had no effect in vitro and
      showed a slight inhibition of lung colonization in vivo. Our results suggest that
      several phenotypic characteristics of the enhanced metastatic potential of B16a
      subpopulations may be mediated by increased expression of alpha IIb beta 3
      receptors and that expression of these receptors may be regulated at the
      transcriptional level.

PMID- 1375590
TI  - Delayed motor function and results of vestibular function tests in children with
      inner ear anomalies.
AB  - The relation between the results of vestibular function tests and gross motor
      development was examined in 4 children with inner ear anomalies. CT scans
      demonstrated the absence of lateral semicircular canals in both ears in all 4
      cases. None responded to caloric stimulation using 40 ml of icewater. In
      contrast, the damped rotation test elicited per-rotatory nystagmus in all cases.
      Per-rotatory nystagmus was provoked in only two cases by the Barany rotation
      test. Development of gross motor function, especially independent walking, was
      more delayed in the two children in whom the Barany rotation test failed to
      elicit per-rotatory nystagmus.

PMID- 1375591
TI  - On the mechanism of lipoxygenase-like action of bleomycin-iron complexes.
AB  - The mechanism of lipid peroxidation catalyzed by bleomycin (BLM)-iron (Fe)
      complexes has been studied in vitro using sodium linoleate as a substrate. BLM
      Fe(II)-O2 and BLM-Fe(III) complexes catalyze lipid peroxidation concomitantly
      with singlet oxygen evolution. The results from spin trapping methods and gas
      chromatography-mass spectroscopy (GCMS) analyses suggest that the initial step of
      lipid peroxidation catalyzed by BLM-Fe complexes is similar to that of soybean
      lipoxygenase, viz., hydrogen abstration. However, another mechanism might be
      concerned in the case of BLM-Fe(II)-O2 complex. BLM-Fe complexes are also capable
      of enhancing singlet oxygen evolution from the hydrogen peroxide (H2O2)
      hypochlorite (OCl-) system.

PMID- 1375592
TI  - New polyenic antibiotics active against gram-positive and gram-negative bacteria.
      VI. Non-lactonic polyene antibiotic, enacyloxin IIa, inhibits binding of
      aminoacyl-tRNA to A site of ribosomes.

PMID- 1375593
TI  - Microbial transformation of immunosuppressive compounds. II. Specific
      desmethylation of 13-methoxy group of FK 506 and FR 900520 by an unidentified
      Actinomycete ATCC 53828 [corrected].

PMID- 1375594
TI  - Detection of antibiotic-induced platelet dysfunction in whole blood using flow
      cytometry.
AB  - Using flow cytometry and activation-dependent monoclonal antibodies, we have
      developed a technique based on forward angle-light scatter (FALS) and
      immunofluorescence that simultaneously detects human platelet activation,
      secretion, and aggregation in whole blood. To detect the effects of cefotetan and
      latamoxef, both of which contain an N-MTT side chain, and of free N-MTT and
      cefoxitin, which does not contain the N-MTT side chain, on platelet activation
      and secretion, platelets were stained by the indirect method using a murine
      produced platelet specific activation-dependent monoclonal antibody, S12, and a
      goat anti-mouse IgG fluorescein-conjugated antibody. S12 binds to a 140kd alpha
      granule membrane protein (GMP-140) that is expressed during secretion. Single
      parameter, 256 channel, log integrated green fluorescence histograms were
      generated, and negative and positive fluorescent populations were defined.
      Latamoxef and cefotetan reduced the number of platelets expressing S12 by more
      than 43%. In contrast, cefoxitin reduced the number of platelets expressing S12
      by only 13.5%. The inhibition of GMP-140 expression per platelet was calculated
      by converting the log data to linear fluorescence intensity. Latamoxef and
      cefotetan inhibited expression of GMP-140 by 88% and 87% respectively. Free N-MTT
      inhibited its expression by 68%. In contrast cefoxitin reduced GMP-140 expression
      per platelet by only 45%.

PMID- 1375595
TI  - Temocillin and cystic fibrosis: outcome of intravenous administration in patients
      infected with Pseudomonas cepacia.
AB  - Twelve courses of intravenous temocillin were given in combination with an
      intravenous aminoglycoside to five patients with cystic fibrosis (CF) for
      pulmonary exacerbations associated with Pseudomonas cepacia. All patients were
      infected concurrently with Pseudomonas aeruginosa in addition to P. cepacia.
      Improvement occurred after six of seven courses given to three patients in which
      temocillin was used as first-line therapy and following three of five courses
      given to two patients after failure of other antipseudomonal agents. All ten pre
      treatment isolates of P. cepacia were resistant to aminoglycosides and eight were
      sensitive to temocillin. Clinical improvement was seen on both occasions in which
      the pre-treatment isolates were resistant to temocillin.

PMID- 1375596
TI  - Effect of neuropeptides released from sensory nerves on blood flow in the rat
      airway microcirculation.
AB  - Stimulation of sensory nerves in the airway mucosa causes local release of the
      neuropeptides substance P and calcitonin gene-related peptide (CGRP). In this
      study we used a modification of the reference-sample microsphere technique to
      measure changes in regional blood flow and cardiac output distribution produced
      in the rat by substance P, CGRP, and capsaicin (a drug that releases endogenous
      neuropeptides from sensory nerves). Three sets of microspheres labeled with
      different radionuclides were injected into the left ventricle of anesthetized
      F344 rats before, immediately after, and 5 min after left ventricular injections
      of capsaicin, substance P, or CGRP. The reference blood sample was withdrawn from
      the abdominal aorta and was simultaneously replaced with 0.9% NaCl at 37 degrees
      C. We found that stimulation of sensory nerves with a low dose of capsaicin
      causes a large and selective increase in microvascular blood flow in the
      extrapulmonary airways. The effect of capsaicin is mimicked by systemic injection
      of substance P but not by CGRP, suggesting that substance P is the main agent of
      neurogenic vasodilation in rat airways.

PMID- 1375598
TI  - Galanin decreases circulating growth hormone levels in acromegaly.
AB  - Galanin is able to elicit GH secretion in normal man. In acromegaly, circulating
      GH levels are elevated, and GH secretory dynamics are usually abnormal. The aim
      of our study was to investigate the effects of galanin on GH secretion in
      acromegalic subjects. Six acromegalic patients (four males and two females) and
      seven healthy adult subjects (five males and two females) underwent in randomized
      order: 1) iv infusion of 100 mL saline from 0-45 min, and 2) iv infusion of
      synthetic porcine galanin (0.5 mg in 100 mL saline) from 0-45 min. In normal
      subjects, peak GH levels after porcine galanin administration (8.2 +/- 1.9
      micrograms/L) were significantly higher than after saline infusion (1.3 +/- 0.1
      micrograms/L; P less than 0.05). In acromegalic patients, GH values fell from
      baseline (32.5 +/- 12 micrograms/L) to a mean nadir of 24.5 +/- 12.7 micrograms/L
      after galanin infusion. The mean change in GH values from baseline after galanin
      treatment in these subjects significantly differed from that observed after
      saline infusion from 15-90 min. Serum PRL levels were not significantly affected
      by galanin in either normal or acromegalic patients. Our results give the first
      evidence that the same dose of galanin, acting as a GH secretagogue in normal
      man, is, on the contrary, able to significantly inhibit GH in acromegalic
      patients. The cause of this paradoxical GH fall after galanin treatment in
      acromegaly remains to be explained. It can be hypothesized that galanin may
      interact at the pituitary level with its own receptors expressed by GH-secreting
      adenomatous cells.

PMID- 1375597
TI  - Hyperserotoninemia and antiserotonin antibodies in autism and other disorders.
AB  - This study examined the linkage between elevated blood serotonin in autism and
      the presence of circulating autoantibodies against the serotonin 5HT1A receptor.
      Information was also obtained on the diagnostic and receptor specificity of these
      autoantibodies. Blood serotonin was measured as was inhibition of serotonin
      binding to human cortical membranes by antibody-rich fractions of blood from
      controls and from patients with childhood autism, schizophrenia, obsessive
      compulsive disorder, Tourette's, and multiple sclerosis. The results showed
      elevated blood serotonin was not closely related to inhibition of serotonin
      binding by antibody-rich blood fractions. Inhibition of binding was highest for
      patients with multiple sclerosis and was not specific to the 5HT1A receptor as
      currently defined. Although inhibition was not specific to autism, the data were
      insufficient to establish if people with autism differed from normal controls on
      this measure.

PMID- 1375599
TI  - Imbalanced follicle-stimulating hormone beta-subunit hormone biosynthesis in
      human pituitary adenomas.
AB  - Clinically nonfunctioning pituitary adenomas represent approximately 25% of all
      pituitary tumors. Recent studies using a number of in vitro techniques show that
      the majority of such tumors produce gonadotropins. Hypersecretion of uncombined
      gonadotropin subunits by these tumors has also been identified raising the
      possibility that gonadotropin biosynthetic alterations may occur in neoplastic
      pituitary tissue. To determine whether underlying intracellular biosynthetic
      alterations lead to imbalanced secretion of the gonadotropin subunits by such
      tumors, we investigated 1) steady state gonadotropin-subunit messenger
      ribonucleic acid (mRNA) levels in tumor tissue from 49 patients with clinically
      nonfunctioning adenomas, 2) secretion of gonadotropins in dispersed pituitary
      tumor cultures, and 3) serum concentrations of gonadotropins and free subunits.
      Northern blots of RNA extracted from surgically obtained pituitary tumor tissue
      were hybridized with complementary DNA probes for FSH beta, LH beta, and alpha
      subunit, and quantitative analysis was done to compare alpha- and beta-subunit
      biosynthesis in individual tumors. Of these tumors, 47 contained sufficient RNA
      for Northern analysis and 77% of these tumors contained one or more of the
      gonadotropin-subunit mRNAs. Steady state alpha-subunit mRNA was detected in 57%
      of tumors, FSH beta mRNA in 49%, and LH beta in 1 (2%). We found FSH beta mRNA in
      excess of alpha-subunit mRNA in one-third of tumors, including 9 tumors where
      alpha-subunit mRNA was undetectable. In cultured cells, FSH beta was secreted in
      excess of alpha-subunit in 41% of tumors. For those tumors in which both mRNA and
      culture data were available, FSH beta mRNA and secreted subunit levels were in
      excess of alpha-subunit in 64% of tumors. We conclude that clinically
      nonfunctioning pituitary adenomas frequently synthesize excess FSH beta subunit
      relative to alpha-subunit. This finding is in contrast to previous data in normal
      pituitary or placental tissue where alpha-subunit is present in excess of beta
      subunits at both the mRNA and protein levels. The free-beta-subunit
      hypersecretion identified in pituitary adenomas may be due to biosynthetic
      abnormalities intrinsic to neoplastic gonadotrophs.

PMID- 1375601
TI  - Human decidua and in vitro decidualized endometrial stromal cells at term contain
      immunoreactive corticotropin-releasing factor (CRF) and CRF messenger ribonucleic
      acid.
AB  - CRF, a hypothalamic neurohormone, has been shown to be present in several tissues
      outside the brain. During pregnancy, both fetal (placental trophoblast, chorion,
      and amnion) and maternal (decidua) intrauterine tissues contain immunoreactive
      CRF. A paracrine/autocrine role of CRF as a regulator of hormonogenesis in human
      placenta and decidua has been suggested. The expression of CRF mRNA in human
      decidua was demonstrated in the present study by Northern blot analysis and was
      found to be higher in specimens collected at term than in those collected during
      the first and second trimesters of gestation. Furthermore, the presence of CRF
      was detected immunocytochemically in cultured decidual cells isolated from term
      decidua as well as in endometrial stromal cells decidualized in vitro by
      treatment with a mixture of medroxyprogesterone acetate, estradiol, and relaxin.
      These results indicate that human decidua is an intrauterine extrahypothalamic
      source of CRF in the maternal compartment and offer new tools to explore the in
      vitro decidualization processes and the regulation of CRF release from decidual
      cells.

PMID- 1375600
TI  - Insulin regulation of insulin-like growth factor binding protein-1 in obese and
      nonobese humans.
AB  - Insulin is the principal regulator of hepatic insulin-like growth factor binding
      protein-1 (IGFBP-1) production, mediating the rapid decrease in plasma IGFBP-1 in
      response to nutritional intake. In this study, we defined IGFBP-1 regulation by
      insulin in upper and lower body obesity, conditions associated with insulin
      resistance and chronic hyperinsulinemia. Overnight postabsorptive IGFBP-1 levels
      in obese and nonobese women showed an inverse, nonlinear relationship with plasma
      insulin concentrations. Maximum suppression of IGFBP-1 was seen at 70-90 pmol/L
      plasma insulin. Both groups of obese women had mean fasting plasma insulin
      concentrations above this threshold level and, consequently, markedly suppressed
      IGFBP-1 levels. To assess the dynamics of insulin regulated IGFBP-1, 10 obese and
      8 nonobese women were studied during sequential saline infusion (0-90 min),
      hyperinsulinemia (insulin infusion; 90-210 min) and hypoinsulinemia (somatostatin
      + GH infusion; 210-330 min). Insulin infusion rapidly decreased plasma IGFBP-1
      levels in nonobese subjects (60% decrease in 2 h), but had little or no further
      suppressive effect in obese subjects. Complete insulin withdrawal resulted in a
      significant rise in plasma IGFBP-1 concentrations in all subjects, but the
      response was blunted in obese compared to nonobese groups. In contrast to plasma
      IGFBP-1, IGF-I concentrations did not vary during hyper- and hypoinsulinemic
      infusion periods and were not significantly different between groups. Basal GH
      levels were significantly higher in nonobese when compared to obese women, but
      did not change with infusions. In conclusion, low IGFBP-1 levels in obesity are
      related to elevated insulin levels which are, in turn, related to body fat
      distribution and insulin resistance. The chronically depressed levels of IGFBP-1
      may promote IGF bioactivity as well as its feedback regulation of GH secretion,
      thus contributing to the metabolic and mitogenic consequences of obesity. In
      addition, our findings imply that hepatic insulin sensitivity in terms of IGFBP-1
      production is preserved despite peripheral insulin resistance in obesity.

PMID- 1375602
TI  - Neuronal excitability: voltage-dependent currents and synaptic transmission.
AB  - Neuronal membrane excitability and the synaptic connections among neurons produce
      behavior and cognition. The intracellular compartment of neurons is negatively
      charged relative to the extracellular space, and this charge, as well as current
      flow, is produced by ions. From the perspective of charged ions, the lipid
      bilayer of the neuronal membrane acts as a capacitor, and transmembrane
      glycoprotein pores or channels act as resistors. The open and closed states of
      ionic channels determine the membrane potential. At equilibrium, the lowest
      resistance or greatest permeability is for potassium, and the resting membrane
      potential is close to the equilibrium potential for potassium. When a channel is
      opened, permeable ions diffuse down their electrochemical gradients and the
      membrane potential is changed. Channels are gated (opened or closed) by voltage,
      neurotransmitters, and second messengers. The neuron integrates synaptic
      potentials produced by transmitter-gated channel activity and either generates a
      subthreshold potential, or a suprathreshold depolarization that generates an
      action potential or a burst of action potentials. Action potential generation is
      mediated by a large, brief sodium influx that is followed by activation of a
      voltage-dependent potassium eflux. The pattern of action potential firing is
      dependent on the interaction of a repertoire of voltage-dependent ion
      conductances. The action potential is the main signaling mechanism to activate
      synaptic transmission at axon terminals. Synaptic transmission is graded
      depending on the amount of calcium entering the presynaptic terminal. The number
      of action potentials, or the shape of the action potential, will determine the
      amount of calcium entering the terminal and the efficacy of synaptic
      transmission. Presynaptic ion channels may also be controlled by
      neurotransmitters or modulators and affect synaptic transmission by altering the
      amount of calcium influx.

PMID- 1375603
TI  - The neurophysiology of glial cells.
AB  - Although glial cells occupy about half of the brain's total volume, they have
      been less well studied than neurons and have been the subject of endless
      speculation regarding their role in the brain's work. An enormous amount of new
      information about glial cells has become available in recent years and has led to
      the realization that these cells interact importantly with neurons in the context
      of all of the brain's main functions. In most instances, the details of these
      complex interactions are still being worked out. We review some of the basic
      physiological properties of glial cells that are important in understanding many
      of their determined or proposed functions.

PMID- 1375604
TI  - The nigral projection to predorsal bundle cells in the superior colliculus of the
      rat.
AB  - Predorsal bundle cells give rise to the major efferent pathway from the superior
      colliculus to the premotor centers of the brainstem and spinal cord responsible
      for initiating orienting movements. The activity of predorsal bundle cells is
      profoundly influenced by an inhibitory pathway from substantia nigra pars
      reticulata that uses gamma aminobutyric acid (GABA) as a neurotransmitter. The
      present study examines the morphological basis for this influence of substantia
      nigra on predorsal bundle cells in the rat. In the first experiments, the laminar
      distributions of the nigrotectal tract terminals and the predorsal bundle cells
      were compared. The predorsal bundle cells were labeled by the retrograde axonal
      transport of horseradish peroxidase from either the decussation of the predorsal
      bundle or the cervical spinal cord, while the terminations of the pathway from
      substantia nigra pars reticulata were labeled by anterograde axonal transport
      from the substantia nigra. Either horseradish peroxidase, wheat germ agglutinin
      conjugated to horseradish peroxidase, or Phaseolus vulgaris leucoagglutinin were
      used as anterograde tracers. The results showed that the distributions of both
      the predorsal bundle cells and the nigrotectal terminals are restricted almost
      entirely to the intermediate grey layer and that they overlap extensively.
      Predorsal bundle cells varied in size. Within the areas of maximum overlap, the
      majority, regardless of size, was closely apposed by nigrotectal terminals. In a
      second series of experiments, the synaptic contacts between nigrotectal terminals
      and the tectospinal component of the predorsal bundle were examined in tissue in
      which both the terminals and the tectospinal cells were labeled for electron
      microscopy. In the final experiments, the distribution and fine structure of the
      nigrotectal terminals were compared to those of terminals that had been labeled
      immunocytochemically with an antibody to glutamic acid decarboxylase, the
      synthesizing enzyme for GABA. The results showed that nigrotectal terminals
      contain large numbers of mitochondria and pleomorphic vesicles, and form synaptic
      contacts with the somas and proximal dendrites of tectospinal cells. These
      synapses have modest postsynaptic densities. In both their distribution and fine
      structure, these terminations resemble the glutamic acid decarboxylase
      immunoreactive terminals that contact tectospinal cells. Taken together, these
      results support the view that the nigrotectal tract is an important source of
      GABAergic input to most, if not all, predorsal bundle cells.

PMID- 1375605
TI  - The somatosensory thalamus of monkeys: cortical connections and a redefinition of
      nuclei in marmosets.
AB  - Thalamic connections of three subdivisions of somatosensory cortex in marmosets
      were determined by placing wheatgerm agglutinin conjugated with horseradish
      peroxidase and fluorescent dyes as tracers into electrophysiologically identified
      sites in S-I (area 3b), S-II, and the parietal ventral area, PV. The relation of
      the resulting patterns of transported label to the cytoarchitecture and
      cytochrome oxidase architecture of the thalamus lead to three major conclusions.
      1) The region traditionally described as the ventroposterior nucleus (VP) is a
      composite of VP proper and parts of the ventroposterior inferior nucleus (VPi).
      Much of the VP region consists of groups of densely stained, closely packed
      neurons that project to S-I. VPi includes a ventral oval of pale, less densely
      packed neurons and finger-like protrusions that extend into VP proper and
      separate clusters of VP neurons related to different body parts. Neurons in both
      parts of VPi project to S-II rather than S-I. Connection patterns indicate that
      the proper and the embedded parts of VPi combine to form a body representation
      paralleling that in VP. 2) VPi also provides the major thalamic input into PV. 3)
      In architecture, location, and cortical connections, the region traditionally
      described as the anterior pulvinar (AP) of monkeys resembles the medial posterior
      nucleus, Pom, of other mammals and we propose that all or most of AP is
      homologous to Pom. AP caps VP dorsomedially, has neurons that are moderately
      dense in Nissl staining, and reacts moderately in CO preparations. AP neurons
      project to S-I, S-II, and PV in somatotopic patterns.

PMID- 1375606
TI  - Direct W-like geniculate projections to the cytochrome oxidase (CO) blobs in
      primate visual cortex: axon morphology.
AB  - The primate lateral geniculate nucleus (LGN) is composed of large, medium, and
      small cells located, respectively, in magnocellular (M), parvocellular (P), and
      specialized layers (intercalated and S-layers in simians, koniocellular (K)
      layers in prosimians). Several studies have examined the physiology and
      connections of M and P LGN cells and have concluded that they provide separate
      contributions to visual perception via separate pathways. Less is known about the
      structure and contributions of the small LGN cells. This study examined the
      distribution and structure of K LGN cell axons in the cortex of the prosimian,
      Galago crassicaudatus. Wheat germ agglutinin conjugated to horseradish
      peroxidase, or Phaseonlus vulgaris leucoaglutinin, was injected into the LGN K
      layers to demonstrate the overall axon projection pattern and the details of
      individual axons, respectively. Location of axons within striate cortex was
      specified relative to boundaries determined by Nissl or cytochrome oxidase (CO)
      stains on the same or adjacent sections. Our results show that K LGN axons end as
      single complex arbors within one CO blob zone in layer III; they never terminate
      in interblob zones. These axons also emit a collateral in layer I that arborizes
      more broadly and spans both CO blob and interblob zones. These data, together
      with data on K cell physiology and intralaminar cortical connections, suggest
      that the LGN small cell pathway could modulate the activity of the other two
      pathways in striate cortex and contribute directly to visual perception.

PMID- 1375607
TI  - Lateral geniculate projections to the superficial layers of visual cortex in the
      tree shrew.
AB  - Our recent studies of tree shrew striate cortex have focused on the organization
      of lateral geniculate projections to layer IV and the projections from IV to
      layer III. Although these pathways play an important role in determining the
      response properties of layer III neurons, there are additional pathways from the
      lateral geniculate nucleus (LGN) that terminate directly in layer III. Previous
      studies provided evidence that these projections originate from layers 6 and 3 of
      the LGN and terminate in different subdivisions of layer III. In this study we
      used injections of biocytin to examine the projections of layers 6 and 3 to the
      cortex in more detail. Consistent with earlier work, we found that LGN layer 6
      projects heavily to lower IIIc, while LGN layer 3 terminates densely in layer
      IIIb and sparsely throughout layers IIIa-I. In addition, we found that neurons in
      layers 6 and 3 have collateral projections: neurons in LGN layer 6 project to the
      bottom of layer IVb and sparsely to I-IIIb; neurons in LGN layer 3 project
      sparsely to layers V and VI and to the middle of IV. These patterns of
      projections are significant in the light of our studies of the connections from
      cortical layer IV to layer III. LGN projections to the superficial layers are
      organized into parallel pathways that exert selective influence over different
      populations of neurons in layers I-III and on the layer IV neurons that supply
      them.

PMID- 1375608
TI  - Fetuin: an acute phase protein in cattle.
AB  - Fetuin is a plasma protein present in high concentrations during fetal
      development in animals of the order Artiodactyla. Its role is not known. The
      human homologue of fetuin--alpha 2HS glycoprotein--has been shown to be a
      negative acute phase protein in adult plasma. In the present study, the
      concentration of fetuin was measured in the serum of healthy cattle (Bovis bovis)
      and in animals with various injuries and inflammatory disorders. The levels were
      decreased by 30% in pregnancy but increased up to 10-fold in some trauma cases. A
      significant negative correlation between the concentrations of fetuin and albumin
      has also been found. Thus, fetuin appears to be a positive acute phase protein in
      cattle.

PMID- 1375609
TI  - Release of substance P-like immunoreactive material from the stomach of the
      rainbow trout.
AB  - The release of substance P-like immunoreactive material (SPLI) from the
      vascularly perfused stomach of the rainbow trout, Oncorhynchus mykiss, was
      studied. In most cases, SPLI was detected in the collected vascular perfusate
      during experimental resting conditions. Distensions of the stomach, accomplished
      by a water-filled intragastric balloon, produced an initial rapid relaxation of
      the stomach, followed by a slow further relaxation and a stimulation of
      contractile activity. The amount of SPLI in the vascular perfusate was
      significantly elevated during the distension period. Tetrodotoxin had no effect
      on the response to distension or on the release of SPLI during distension,
      indicating release from tetrodotoxin-insensitive neurons or endocrine cells. The
      results suggest that a substance P-like peptide may be involved in the
      contractile response and/or in the maintenance of muscular tone during gastric
      distensions in the rainbow trout. Infusion of capsaicin had no effect on the
      release of SPLI. However, capsaicin caused an increase in vascular flow, an
      effect that could be repeated on a second infusion of capsaicin, indicating that
      the action may not be specific to sensory neurons.

PMID- 1375610
TI  - The effect of human anaphylatoxins and neutrophils on histamine release from
      isolated human skin mast cells.
AB  - The concept of mast cell heterogeneity has been studied extensively. Recently
      developed techniques to enzymatically disperse skin mast cells from human skin
      have shown that skin mast cells are somehow different from those of other organs
      such as lung and intestine. In this report, we have isolated and partially
      purified human skin mast cells from human neonatal foreskins by collagenase and
      hyaluronidase digestion. These mast cells are morphologically intact by
      histological, immunohistochemical and electron microscopic criteria. These human
      skin mast cells secrete histamine significantly (max. net histamine release, 20
      30%) in a dose-related, temperature- and time-dependent fashion following
      stimulation with purified human C5a and C3a (over the ranges of 5 x 10(-8) M to
      10(-7) M and 3 x 10(-7) M to 6 x 10(-6) M, respectively). On the other hand,
      interactions between human skin mast cells and other leukocytes have long been
      suspected of playing a very important role in cutaneous inflammation. Recently, a
      human neutrophil-derived histamine-releasing activity termed HRA-N was partially
      purified. HRA-N has been shown to cause human and rat basophil leukemia cells to
      degranulate. This study was also undertaken to assess the ability of HRA-N to
      directly induce histamine release from isolated human skin mast cells. HRA-N
      causes dose- and time-dependent histamine release as do human anaphylatoxins.
      These results suggest that HRA-N may lead to a better comprehension of allergic
      and inflammatory reactions and their modulation in the skin.

PMID- 1375611
TI  - Distributions of interstitial cells of Cajal in stomach and colon of cat, dog,
      ferret, opossum, rat, guinea pig and rabbit.
AB  - Electrical slow waves vary in prominence from one location to another in stomach
      and colon. If interstitial cells of Cajal are involved in generation of the slow
      waves, they might be more abundant in regions where slow waves are prominent than
      in regions where slow waves are small or absent. We calculated the density of
      distribution of interstitial cells of Cajal in colon and stomach of cat, dog,
      ferret, guinea pig, opossum, rabbit, and rat, using the zinc iodide-osmic acid
      reaction for light microscopy. The cells in the stomach were concentrated in the
      myenteric plexus and in the circular muscle layer. Along the greater curvature,
      cells were relatively sparse in the fundus, more frequent in the corpus and
      densest in the antrum. Along the lesser curvature, they were denser distally than
      proximally in all species except guinea pig. In the colon most cells lay with an
      axonal network at the circular muscle-submucosal interface. The axons were sparse
      in the cecum but uniformly conspicuous from the ileocolonic junction to the
      internal and sphincter. The density of the interstitial cells of Cajal in cat,
      dog, opossum, and rabbit rose from a relatively low level in the cecum to a
      maximum in the mid-colon, declining toward the rectum. In guinea pig, rat, and
      ferret, the levels throughout the most proximal colon were high. Since gastric
      slow waves are absent from the fundus, diminutive in the body, and prominent in
      the antrum, the density of interstitial cells of Cajal in the stomach roughly
      parallels the prominence of slow waves. Colonic slow waves are most prominent in
      the right colon and mid-colon, and so the density distribution of interstitial
      cells of Cajal in the colon also roughly parallels the prominence of slow waves.

PMID- 1375612
TI  - Hepatitis C virus antibodies in patients on hemodialysis.

PMID- 1375613
TI  - A cluster of severe postoperative bleeding following open heart surgery.
AB  - OBJECTIVE: To investigate a cluster of postoperative bleeding following open
      heart surgery. DESIGN: A cohort and case/control study. SETTING: Palo Alto
      Veterans Administration Medical Center, Palo Alto, California. PARTICIPANTS: Six
      (21.4%) of 28 patients undergoing open heart surgery who developed severe,
      nonsurgical, postoperative bleeding from July 1 through August 30, 1988 (outbreak
      period). All case-patients had chest tube drainage of greater than or equal to
      1000 ml within 4 hours of surgery but did not have identifiable bleeding
      vessel(s) on exploration. RESULTS: Upon comparison of the pre-outbreak (January
      1986 through June 1988) and the outbreak period, a significant increase was found
      in the incidence of postoperative nonsurgical bleeding (5/440 versus 6/28, p =
      .0006), but not of postoperative surgical bleeding (8/440 versus 0/28, p = 1.0).
      Of all patients undergoing open heart surgery during the outbreak period, case
      patients were found to be older (67.8 versus 60.6, p = .02) and to have received
      a larger volume of hetastarch (HES), a synthetic colloidal plasma-volume expander
      (mean = 19.4 ml/kg versus 14.1 ml/kg, p = .02). CONCLUSIONS: We conclude that the
      use of large volumes of HES during surgery in the elderly open heart surgery
      patient may increase the risk for severe, nonsurgical postoperative bleeding,
      probably caused by alterations of the coagulation system. As the incidence of
      open heart surgery increases among the elderly, surgeons and anesthesiologists
      should be alert to possible adverse reactions from exposures not associated with
      adverse reactions in younger patients.

PMID- 1375615
TI  - An improved method for the purification of basophilic granulocytes from human
      blood.
AB  - Studies on human basophils are hampered by the low number of basophils in
      peripheral blood. Here we describe the purification of human basophilic
      granulocytes with immunomagnetic beads to improve an already established method
      of purification. A 70% pure basophil suspension was incubated with monoclonal
      antibodies (CD2, CD14, CD16 and CD19) recognizing the contaminating cells. After
      incubation with magnetic beads coated with goat anti-mouse IgG, the bead-cell
      rosettes were removed by a magnet. In this way, the basophil purity increased to
      94%. The loss of basophils during the bead procedure was about 20%. The amount of
      histamine per basophil and the spontaneous release of histamine during subsequent
      incubation of the cells was not altered by the purification procedure. The
      kinetics and the dose response of histamine release after the addition of anti
      IgE or FMLP was also unchanged. Binding of CD63 was not altered, indicating that
      the purification procedure did not result in activation of the basophils. This
      improved method for the purification of human basophils should permit the
      measurement of non-basophil-specific parameters, such as changes in intracellular
      free Ca2+, without the problem of interference from contaminating cells.

PMID- 1375614
TI  - Induction and identification of mast cells from long-term culture of mouse spleen
      cells without conditioned medium.
AB  - A simple method is described for the preparation of large numbers of mast cells
      from mouse spleen cells in vitro. Mouse spleen cells were cultured with RPMI 1640
      medium supplemented with 10% FCS and 2-ME. Half of the total volume of the medium
      was changed every 4-5 days. Mast cell numbers increased with the culture time and
      reached a peak between 16 and 20 days. Using this method, 2 x 10(6) mast cells
      could be induced from 1 x 10(7) nucleated normal spleen cells. T cells and
      supernatant derived from ConA-stimulated T cells were unnecessary for mast cell
      induction. Phenotype analysis by FACS showed that Thy1,2, L3T4, Ly-2, Ig, B220,
      Asialo GM1, and WGA receptors were all negative but functional IgE receptors were
      positive. The granules in the cells could be stained by alcian blue but not by
      safranin. There was 1.632 +/- 0.024 micrograms stored histamine in 1 x 10(6) of
      the cells. Histamine was released from the cells in an antigen-induced and IgE
      mediated process. Compound 48/80 and A23187 induced degranulation of the cells,
      and the mast cells were able to respond to ConA.

PMID- 1375616
TI  - Urticaria.

PMID- 1375617
TI  - Immunosuppressive macrolides of the type FK 506: a novel class of topical agents
      for treatment of skin diseases?
AB  - The immunosuppressive macrolide antibiotics FK 506 and rapamycin were tested for
      topical activity in experimental allergic contact dermatitis of farm pigs. This
      species was used because pig skin, in comparison to rodent skin, resembles human
      skin more closely. For comparison, cyclosporine A (CyA), which is orally but not
      topically active in patients with skin disease, dexamethasone, and clobetasol
      propionate were used. Treatment was performed twice, 30 min and 6 h after
      elicitation of challenge reaction. Topical application of 0.4 to 0.04% FK 506
      caused a pronounced inhibition of inflammatory skin reactions of hypersensitivity
      to dinitrofluorobenzene. The treatment response was similar to the activity of
      0.13% clobetasole. Dexamethasone (1.2%) was less active than clobetasol. In
      contrast, rapamycin and CyA were inactive at concentrations of 1.2 and 10%,
      respectively. Because the pig data on corticosteroids and cyclosporine A are in
      agreement with clinical findings, these studies indicate that immunosuppressive
      macrolides of the type FK 506 may be useful drugs for the topical treatment of
      human skin diseases that respond to local corticosteroids and oral treatment with
      cyclosporine A.

PMID- 1375618
TI  - Differential expression of laminin isoforms and beta 4 integrin epitopes in the
      basement membrane zone of normal human skin and basal cell carcinomas.
AB  - The basement membrane zone biology of normal human skin and basal cell carcinomas
      was explored by indirect immunofluorescence with monoclonal antibodies
      recognizing five subunit polypeptides of three different laminin isoforms as well
      as the beta 4 integrin epitopes. The laminin antibodies were specific for A, B1,
      and B2 chains of classic laminin, for the M chain of merosin, or for the S chain
      in S-laminin. Immunostaining of normal human skin revealed a strong signal with
      antibodies for A, B1, and B2 chain epitopes. A weak immunosignal was detected
      with an anti-M chain antibody, whereas the S-chain epitopes were undetectable,
      even following pretreatment of sections with hyaluronidase. Thus, the laminin at
      the epidermal-dermal junction of normal human skin is primarily of the classic
      type, with some merosin molecules being present. The staining of six nodular
      basal cell carcinomas revealed the presence of A, B1, and B2 chain epitopes in a
      linear pattern, but, in contrast to normal skin, the antibody recognizing M-chain
      epitopes yielded a strong immunosignal, and S-chain epitopes could also be
      readily detected. Staining for beta 4 integrins, potential receptors for laminin,
      revealed a strong staining reaction in normal skin as well as in the superficial
      portions of the basal cell carcinoma. However, the immunofluorescence pattern in
      the deeper portions of the lesions was scattered and interrupted. Thus, altered
      composition of the basement membrane of nodular basal cell carcinomas with
      respect to laminin isoforms and their interactions with putative cell-surface
      receptors, the beta 4 integrins, may change the containment of the tumor islands,
      contributing to the local aggressive behavior of basal cell carcinomas.

PMID- 1375619
TI  - Induction of 72-kD heat shock protein and cytoskeleton damage by cytotoxic
      prostaglandin delta 12-PGJ2 in transformed human epidermal cells in culture.
AB  - Cyclopentenone prostaglandins (PG) such as delta 12-PGJ2 and PGA are potent
      inhibitors of growth in a variety of cultured cells, including human epidermal
      cells. To clarify the mechanism of PG cytotoxicity in human epidermal cells, we
      examined the effects of delta 12-PGJ2 on the induction of a heat shock protein
      (HSP), and on the organization of cytoskeletons in the HSC-I-transformed human
      epidermal cell line. Immunoblot analysis using a monoclonal antibody specific for
      the 72-kD heat shock protein (HSP72) revealed that a 12-h incubation with 5
      micrograms/ml of delta 12-PGJ2 induced HSP72 formation in HSC-I cells. HSP72 was
      also induced by heat shock treatment at 43 degrees C for 90 min. The quantity of
      HSP72 produced was markedly decreased by co-treatment with 1 microgram/ml of
      cycloheximide in delta 12-PGJ2-treated cells, and similarly reduced in HSC-I
      cells following heat treatment. Immunofluorescence using a monoclonal antibody to
      HSP72 demonstrated that HSP72 was localized mainly in the cytoplasm of HSC-I
      cells. Following treatment with 5 micrograms/ml of delta 12-PGJ2, however, HSP72
      was found in the nucleolus as well as in the cytoplasm. The accumulation of HSP
      in the nucleolus was similarly prominent in HSC-I cells after treatment at 43
      degrees C for 90 min. Addition of delta 12-PGJ2 to confluent HSC-1 cells resulted
      in the disappearance of actin filaments and the disarrangement of keratin
      filaments, as visualized with fluorescent-labeled phallacidine or
      immunofluorescence. These results suggest that the cytotoxicity of cyclopentenone
      PG is related to the induction of HSP72, and to cytoskeleton damage in
      transformed human epidermal cells in culture.

PMID- 1375620
TI  - Delayed onset of epidermal differentiation in psoriasis.
AB  - In normal epidermis, as previously reported, the first signs of differentiation
      occur within the basal layer in a subpopulation of keratinocytes that start to
      express K1 and K10 "supra-basal" keratin transcripts (20-30% of the basal cells)
      and proteins (5-10% of the basal cells). We found that in psoriatic lesions, the
      basal layer was devoid of cells expressing these early differentiation markers.
      This was already the case at the periphery of the lesions, where epidermis,
      although slightly acanthotic, still completes the keratinization process. In the
      center of the lesions, not only the basal layer, but also several rows of
      suprabasal cells, were negative for keratin K10 transcripts or protein. Moreover,
      the upper nucleated layers of involved epidermis were also devoid of K10 keratin
      transcripts or proteins. In normal epidermis, as previously reported, transcripts
      for the "basal" K5 keratin were mainly restricted to the basal layer, whereas the
      protein persisted in a few suprabasal layers. We found that in psoriatic
      epidermis, K5 keratin transcripts persisted in several suprabasal layers up to
      the level where K10 keratin transcripts appeared. These data, although not
      contradictory with previous reports showing a reduction of K1-K10 keratins and
      other differentiation markers in psoriasis, demonstrate that these quantitative
      changes are in fact the result of major qualitative differences in the
      distribution of these markers in psoriatic versus normal skin. Our results
      indicating that the onset of differentiation is delayed in psoriasis show that,
      contrary to conclusions accepted so far, not only the suprabasal compartment, but
      also the basal one, is abnormal in psoriatic epidermis.

PMID- 1375621
TI  - [Neurotransmitters and the pain transmission system].

PMID- 1375622
TI  - Antigenic analysis of Clostridium chauvoei flagella with protective and non
      protective monoclonal antibodies.
AB  - Five monoclonal antibodies (mAbs) directed against the flagellin of Clostridium
      chauvoei were used to analyse the structural and antigenic characteristics on the
      bacterial flagellar surface. Immune electron microscopy showed that three
      protective mAbs recognized the surfaced-exposed epitopes on the flagellar
      filament of this bacteria. In contrast, two non-protective mAbs recognized
      internal epitopes of the flagellar filament. These findings have been confirmed
      by ELISA using mAbs absorbed with whole cells of C. chauvoei possessing flagella.
      Competitive binding assays showed that protective mAbs indicated reciprocal
      competition, while each of the non-protective mAbs had topographically distinct
      epitopes. Moreover, immunoblotting analysis with cyanogen-bromide-cleaved
      flagellin showed that protective mAbs may preferentially recognize conformational
      epitopes, whilst one of the non-protective mAbs may recognize a linear and
      conformation-independent epitope in the flagellin of C. chauvoei.

PMID- 1375624
TI  - Aminoglycoside and aminocyclitol antibiotics: hygromycin B is an atypical
      bactericidal compound that exerts effects on cells of Escherichia coli
      characteristics for bacteriostatic aminocyclitols.
AB  - The effects of aminoglycoside and aminocyclitol antibiotics on intact cells of
      Escherichia coli were compared. The aminoglycosides streptomycin, gentamicin,
      kanamycin and neomycin had similar, but not identical, effects. They all caused
      misreading during protein synthesis, permeabilization of the cell membrane,
      inhibition of the initiation of DNA replication, and loss of cell viability.
      Cells treated with these antibiotics continued to synthesize two proteins
      (apparent molecular masses 72 and 60 kDa) that were not made by cells treated
      with the aminocyclitol hygromycin B, which did not cause misreading. Cells
      treated with the aminoglycosides regained their membrane tightness after residual
      protein synthesis in these cells had been inhibited by chloramphenicol,
      suggesting that under these conditions the mistranslated membrane proteins were
      rapidly degraded. The bacteriostatic aminocyclitols spectinomycin and kasugamycin
      did not cause membrane permeabilization, suggesting that these compounds do not
      cause misreading. Hygromycin B resembled these aminocyclitols in that it
      inhibited protein synthesis without causing misreading, membrane permeabilization
      or inhibition of initiation of DNA synthesis. However, hygromycin B also
      decreased cell viability. In minimal medium this lethal effect began late in
      comparison to the process of inhibition of protein synthesis. It is concluded
      that hygromycin B is an atypical bactericidal antibiotic that strongly resembles
      the bacteriostatic aminocyclitols spectinomycin and kasugamycin in its action.

PMID- 1375623
TI  - The bactericidal action of streptomycin: membrane permeabilization caused by the
      insertion of mistranslated proteins into the cytoplasmic membrane of Escherichia
      coli and subsequent caging of the antibiotic inside the cells due to degradation
      of these proteins.
AB  - The mechanism by which the aminoglycoside antibiotic streptomycin permeabilizes
      the cytoplasmic membrane of Escherichia coli cells was reinvestigated. For this
      purpose, the extent of streptomycin-induced K+ loss from cells growing at low
      external K+ concentrations was taken as a measure of membrane permeabilization.
      Experiments with different K(+)-uptake mutants showed that the antibiotic
      specifically increased the passive permeability of the cell membrane to K+ and
      other ions. These permeability changes were small and the membrane potential of
      the treated cells remained high. The membrane permeabilization was not due to a
      direct interaction of the antibiotic with the cell membrane, since cells that
      carry an rpsL mutation and synthesize proteins in a streptomycin-insensitive way
      did not lose K+ after the addition of the antibiotic. Due to misreading and
      premature termination of translation the cells synthesized aberrant proteins
      under the conditions where membrane permeabilization occurred. Two conditions are
      described under which the cells both degraded these mistranslated proteins
      rapidly and reaccumulated K+, lending support to the hypothesis that membrane
      permeabilization is due to the presence of the mistranslated proteins in the cell
      membrane. Evidence is presented that the irreversibility of (dihydro)streptomycin
      uptake by cells washed free from the antibiotic might also be due to rapid
      degradation of the mistranslated proteins, leading to 'caging' of the antibiotic
      inside the cells.

PMID- 1375625
TI  - Isolation and characterization of temperature-sensitive mutants of Streptomyces
      coelicolor A3(2) blocked in macromolecular synthesis.
AB  - A collection of temperature-sensitive mutants of Streptomyces coelicolor A3(2)
      was isolated. The majority of the mutants showed an osmotically remedial
      phenotype. Mutants defective in macromolecular synthesis were identified and
      characterized further. Four mutants were found in which DNA replication was
      defective, but which continued to synthesize RNA and protein at the restrictive
      temperature (39 degrees C). The kinetics of cessation of DNA synthesis allowed a
      tentative identification of slow (initiation) and fast (elongation) stop dna
      mutants. The inhibition of DNA replication in the four mutants was found to be
      reversible on returning to the permissive temperature (30 degrees C), but only
      after a delay of about 2 h. Three other mutants were identified which showed not
      only cessation of DNA replication at the restrictive temperature, but also
      defects in other macromolecular synthesis events.

PMID- 1375626
TI  - Anti-aids agents, 6. Salaspermic acid, an anti-HIV principle from Tripterygium
      wilfordii, and the structure-activity correlation with its related compounds.
AB  - Salaspermic acid [1], an inhibitor of HIV reverse transcriptase and HIV
      replication in H9 lymphocyte cells, was isolated from the roots of Tripterygium
      wilfordii for the first time. The structure of 1 derived from spectral data was
      established unequivocally by an X-ray analysis of crystals of the monohydrate. A
      structure-activity correlation of 1 with ten related compounds indicated that the
      acetal linkage in ring A and the carboxyl group in ring E of 1 may be required
      for the anti-HIV activity.

PMID- 1375627
TI  - Evidence of hyaluronic acid and hyaluronic acid binding sites on human corneal
      endothelium.
AB  - A highly specific hyaluronic acid (HA) recognizing protein (HABR) was used to
      study whether the human corneal endothelium is covered by HA and to quantify the
      amount. Tritiated high molecular weight HA was used to determine the capacity of
      the human endothelium to bind exogenous HA. Human corneas were obtained from
      keratoconus patients having corneal transplantation and from postmortem eyes. The
      corneas were immersed in a 4% formaldehyde solution containing 1% cetylpyridine
      chloride for histochemistry, frozen for biochemistry, or used for 3H-HA (Mr 3 x
      10(6) binding. For the biochemical determinations, 125I-labeled HABR was used.
      Tritiated HA was used for the binding experiment. A specific layer of HA covering
      the endothelial cells of the corneal buttons was demonstrated. The biochemical
      analysis also revealed the presence of HA. Finally, the human endothelial cells
      had specific hyaluronic acid binding sites.

PMID- 1375628
TI  - Acetylcholine and kinin augmentation of Cl- secretion stimulated by prostaglandin
      in a canine renal epithelial cell line.
AB  - 1. The actions of kinins and of acetylcholine upon transepithelial ion transport
      in a renal-derived cultured epithelium (Madin-Darby canine kidney cells, MDCK)
      have been investigated. 2. In voltage-clamped epithelial layers mounted in Ussing
      chambers and with prior stimulation of inward short-circuit current (SCC) by 5 or
      10 microM-prostaglandin E1 (PGE1), both bradykinin (1 microM) and acetylcholine
      (0.1 mM) stimulate an additional, but transient, inward SCC. In the absence of
      PGE1 minimal effects of both bradykinin and acetylcholine upon SCC are observed.
      The SCC response to bradykinin and acetylcholine are attenuated with prior
      stimulation by 10 microM-adrenaline. 3. Measurements of bradykinin and
      acetylcholine-stimulated inward SCC with cation and anion replacement of the
      bathing media and the use of the Cl channel blocker 5-nitro-2(3
      phenylpropylamino)-benzoic acid (NPPB) together with bumetanide to inhibit Na(+)
      K(+)-Cl- 'co-transport', are consistent with the bradykinin- and acetylcholine
      stimulated SCC being the result of basal to apical Cl- secretion. 4. Bradykinin
      (1 microM) is capable of stimulation of inward SCC from both epithelial surfaces,
      whilst acetylcholine is only effective from the basolateral surface. Kallidin
      (lys-bradykinin) was similar in effect to bradykinin from both epithelial
      surfaces whereas bradykinin (1-8) was ineffective, suggesting that B2 bradykinin
      receptors mediate the effect of bradykinin upon SCC. Dose-response relationships
      show that the response to kallidin and bradykinin was of higher sensitivity for
      additions to the apical cell aspects. 5. The data are discussed in relation to a
      model for epithelial Cl- secretion, and to the mechanism of natriuresis observed
      with kinins and acetylcholine in vivo.

PMID- 1375629
TI  - The ATP-induced inward current in mouse lacrimal acinar cells is potentiated by
      isoprenaline and GTP.
AB  - 1. ATP activates calcium (Ca2+) influx in mouse lacrimal acinar cells in the
      absence of phosphoinositide hydrolysis. Extracellular ATP (1 mM) activates
      receptor-operated cation channels, promoting entry of Na+ and Ca2+ (inward
      current). This Ca2+ influx in turn activates K+ channels resulting in a delayed,
      outward, current component. The present study uses patch-clamp current recording
      techniques to investigate the role of beta-adrenoceptor mechanisms, intracellular
      cyclic AMP and GTP in the regulation of the ATP-induced inward currents. 2. The
      beta-adrenoceptor agonist, isoprenaline (1 microM), does not increase the resting
      membrane currents but markedly enhances the ATP-induced inward and outward
      currents. This effect of isoprenaline is blocked by the beta-adrenoceptor
      antagonist propranolol. 3. Internal application of cyclic AMP mimics the
      potentiating effect of isoprenaline. 100 microM-cyclic AMP increases the ATP
      induced inward and outward currents to about 200% as compared to control
      responses. 4. Pre-treatment of the cells with the phosphodiesterase inhibitor 3
      isobutyl-1-methylxanthine (IBMX; 1 mM), also results in a marked potentiation of
      the ATP-induced inward currents to 170% as compared to control responses. 5. The
      ATP-induced inward current responses are not blocked by either the removal of
      extracellular Ca2+ or by chelation of intracellular Ca2+ (by inclusion of 10 mM
      EGTA in the recording pipette). Both protocols did however block the potentiating
      effect of internal cyclic AMP on the ATP-induced inward current responses. 6.
      Intracellular ATP (10 mM) reduces the amplitude of the inward currents evoked by
      external ATP application by about 60% and the currents were no longer potentiated
      by internal cyclic AMP. 7. Intracellular GTP or GTP-gamma-S (100 microM in the
      pipette solution) potentiates the current responses to ATP, increasing both the
      amplitude and duration of the inward currents. 8. In excised inside-out patches,
      with ATP in the recording pipette (i.e. external ATP), the catalytic subunit of
      the cyclic AMP-dependent protein kinase activated the cation channels. The effect
      of the catalytic subunit was readily reversible and abolished by an inhibitor of
      the protein kinase. 9. External ATP activates Ca2+ influx in lacrimal acinar
      cells by a mechanism that is distinct from that activated by phosphoinositide
      coupled receptors. The effect is mediated by direct activation of cation channels
      in the cell surface membrane which allow for significant entry of Ca2+.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1375630
TI  - Substance P inhibits activation of calcium-dependent potassium conductances in
      guinea-pig myenteric neurones.
AB  - 1. Intracellular recordings were made from myenteric AH neurones of the guinea
      pig ileum in vitro. Some experiments were done with a single-electrode voltage
      clamp to measure membrane currents. 2. Substance P (SP) applied by superfusion
      (10 nM-300 nM), pressure ejection (100 nM-10 microM, 760 mmHg, for 10-20 ms) or
      ionophoresis (1 mM, 100 nA, for 0.2 s) caused a membrane depolarization and an
      inward current, associated with a decrease in potassium conductance. 3. The SP
      induced depolarization was abolished within 15 min by superfusion with calcium
      free/high-magnesium (10 mM) solution or solutions containing cobalt, manganese or
      nickel at 1-3 mM. The response persisted even after 40-60 min of superfusion with
      calcium-free/normal-magnesium (1.2 mM) solution. In all these solutions, synaptic
      potentials were abolished within 5 min. 4. SP inhibited a slowly developing
      outward current and an outward tail current during and after a long depolarizing
      command pulse (2-10 s), and an outward after-current following single or multiple
      brief depolarizing command pulses (10-50 ms). These outward currents were
      suppressed in calcium-free/high-magnesium solution. 5. SP depressed both a
      calcium-dependent slow after-hyperpolarization following the action potential and
      an outward after-current preceded by a brief depolarizing command. Both the SP
      induced depolarization and the SP-induced inward current were augmented when the
      peptide was pressure-ejected during the recovery phase of the slow after
      hyperpolarization and during that of the slow outward after-current, but both of
      them were inhibited or almost abolished when SP was applied immediately after
      spike initiation or a brief depolarizing command. 6. The SP-induced response was
      depressed by barium (1-2 mM). The SP response was not inhibited by
      tetraethylammonium at low concentrations (5-10 mM), but was depressed at high
      concentration (20 mM). 7. Superfusion (1-10 nM) or pressure application of a
      calcium ionophore, A23187, inhibited or even reversed the SP depolarization and
      the SP-induced inward current. 8. These results indicate that SP inhibits
      activation of a calcium-dependent potassium conductance which contributes to both
      the slow after-hyperpolarization and the resting membrane potential. SP may
      affect the process by which calcium activates this potassium conductance.

PMID- 1375631
TI  - Neuronal nicotinic acetylcholine receptor currents in phaeochromocytoma (PC12)
      cells: dual mechanisms of rectification.
AB  - 1. Neuronal nicotinic acetylcholine receptor (nAChR) currents in PC12 cells were
      studied using single-channel and whole-cell gigaohm seal voltage-clamp
      techniques. Nicotinic AChR agonists were applied using external pipettes. 2. The
      single-channel conductance of neuronal nAChRs in outside-out patches under Mg(2+)
      free ionic conditions was 48 pS. In the absence of internal Mg2+ single-channel
      currents (outside-out patches) did not rectify. 3. Whole-cell nAChR currents
      recorded with normal internal solution (lacking Mg2+ chelators as described
      below) were strongly inwardly rectifying. Current vs. voltage relations showed a
      sharp inflexion near 0 mV, and outward current was never observed. 4. Extensive
      dialysis with internal solution containing EDTA and Na2-ATP, chelators of
      intracellular Mg2+ (Mgi2+), relieved rectification of instantaneous nAChR
      currents during voltage jumps from negative potentials. The instantaneous I-V
      relation became linear with voltage, in agreement with the expectation from
      single-channel measurements made under similar ionic conditions. 5. Agonist
      induced currents recorded under Mgi(2+)-free conditions relaxed towards zero
      current during depolarizing voltage steps. Rectification of ACh-induced currents
      at the steady state could be described by a Boltzmann relation, with one-half of
      channels available at +3.4 mV and an effective gating charge of -0.97. Channel
      availability was approximately 95% at the resting potential. Opening and closing
      relaxations under Mgi(2+)-free conditions could be fitted by single exponential
      functions whose time constants were weakly voltage dependent. 6. A model of
      rectification was constructed incorporating two voltage-dependent processes:
      block by Mgi2+ and intrinsic channel gating. The I-V relations predicted by this
      model for both normal and Mgi(2+)-free conditions were in good agreement with the
      experimental data. We suggest that rectification of nAChR currents in these cells
      is due to concurrent activity of these two voltage-dependent processes. The
      relative contributions of these two mechanisms are frequency dependent, with
      block by Mgi2+ dominant for fast events and intrinsic channel gating more
      important at the steady state.

PMID- 1375632
TI  - A novel modulatory binding site for zinc on the GABAA receptor complex in
      cultured rat neurones.
AB  - 1. The properties of gamma-aminobutyric acidA (GABAA) receptor-ion channel
      complexes and the interaction with the transition metal zinc, were studied on rat
      sympathetic and cerebellar neurones in dissociated culture using patch clamp
      recording techniques. 2. The antagonism of GABA-induced membrane currents by zinc
      on sympathetic neurones was subject to developmental influence. Using embryonic
      sympathetic neurones acutely cultured for 24-72 h, GABA responses were more
      depressed by zinc when compared to responses evoked on adult neurones cultured
      for the same period. For neurones developing in vivo, the percentage inhibition
      of GABA responses produced by zinc in embryonic neurones was estimated to decline
      by 50% after 48.2 days following birth. 3. Embryonic sympathetic neurones
      maintained in culture for prolonged periods (40-50 days in vitro, DIV) became
      less sensitive to zinc when compared to neurones cultured for shorter periods (10
      20 DIV). The decrease in the zinc inhibition for neurones maintained in vitro
      proceeded at an apparent rate of 0.55% per day. 4. Activation of the GABA
      receptor by muscimol (0.2-2 microM) was also antagonized by zinc (50-100 microM).
      5. Lowering the pH of the perfusing Krebs solution did not affect the inhibition
      of GABA responses by zinc on sympathetic neurones. 6. Modulation of the GABAA
      receptor by some benzodiazepines, a barbiturate, a steroid based on pregnanolone,
      or antagonists bicuculline and picrotoxinin, did not interfere with the
      antagonism exerted by zinc on sympathetic neurones. A novel binding site for zinc
      on the GABAA receptor is proposed. 7. Analysis of the GABA-activated current
      noise on sympathetic neurones revealed two kinetic components to the power
      spectra requiring a double Lorentzian fit. The time constant describing the fast
      component (tau 2, 2.1 ms) was unaffected by zinc, whereas the slow component time
      constant (tau 1, 21.7 ms) was slightly reduced to 17.1 ms. 8. The apparent single
      channel conductance for GABA-activated ion channels was determined from the power
      spectra (gamma s = 22.7 pS) and also from the relationship between the mean GABA
      induced inward current and the variance of the current (gamma v = 24 pS). Zinc
      (25-100 microM) did not affect the single-channel conductance. 9. Single GABA
      activated ion channels were recorded from outside-out patches taken from the soma
      of large cerebellar neurones. Single GABA channels were capable of activation to
      multiple current amplitudes which were assessed into the following conductance
      levels: 8, 18, 23, 29 and 34 pS.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375635
TI  - Effects of sympathetic activity and galanin on cardiac vagal action in
      anaesthetized cats.
AB  - 1. Stimulation of the right cardiac sympathetic nerve for 3 or 5 min at 16 Hz in
      the presence of effective beta-adrenoceptor blockade evoked prolonged attenuation
      of subsequent cardiac vagal action in anaesthetized cats. Concurrent sympathetic
      and vagal stimulation, both at 16 Hz for the same period of time as sympathetic
      stimulation alone, reduced or abolished the inhibition of vagal action which
      followed when sympathetic stimulation was given alone. 2. A series of three
      successive intravenous injections of galanin all caused attenuation of vagally
      induced slowing of the heart, but the effect of each injection was less than that
      of the previous one. A fourth injection of galanin given after a 45 or 60 min
      rest period showed return of sensitivity. 3. Sympathetic stimulation at 16 Hz for
      5 min was less efficient in causing attenuation of vagal slowing when applied
      following the administration of exogenous galanin. This is consistent with
      galanin being the mediator of vagal attenuation following sympathetic
      stimulation.

PMID- 1375634
TI  - Dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels in a
      mammalian neuroblastoma-glioma cell line.
AB  - 1. Pharmacological and kinetic properties of high-voltage-activated (HVA) Ca2+
      channel currents were studied using the whole-cell and perforated patch-clamp
      methods in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15,
      differentiated by dibutyryl cyclic AMP or by prostaglandin E1 and theophylline.
      2. The HVA currents were separated into two components by use of two organic Ca2+
      channel antagonists, omega-conotoxin GVIA (omega CgTX) and a dihydropyridine
      (DHP) compound, nifedipine. One current component, IDHP, was blocked by
      nifedipine (Kd = 8.2 nM) and was resistant to omega CgTX. Conversely, the other
      component, I omega CgTX, was irreversibly blocked by omega CgTX and was resistant
      to DHPs. Thus, IDHP could be studied in isolation by a short application of omega
      CgTX, while I omega CgTX could be studied in the presence of nifedipine. 3. The
      voltage for half-activation of IDHP was smaller than that of I omega CgTX by 13
      mV. IDHP was activated at potentials that were subthreshold for voltage-dependent
      K+ currents of the cell, whereas I omega CgTX was not. 4. Time courses of
      activation and deactivation of IDHP were faster than those of I omega CgTX. 5.
      Voltage-dependent inactivation was small for both IDHP and I omega CgTX at any
      potential. 6. Ca(2+)-dependent inactivation of IDHP was faster and more prominent
      than that of I omega CgTX. The time course of the Ca(2+)-dependent inactivation
      of IDHP, but not I omega CgTX, was slowed as the membrane potential was made more
      positive between -20 and 30 mV, although amplitude of the current was increased.
      7. Alkaline earth metal ions carried the two components of IHVA in the same
      order: Ba2+ greater than Sr2+ greater than Ca2+. 8. Metal ions blocked the two
      components of IHVA in the same order of potency: Gd3+ greater than La3+ greater
      than Cd2+ greater than Cu2+ greater than Mn2+ greater than Ni2+. 9. An alkylating
      agent, N-ethylmaleimide (NEM, 0.1 mM), selectively augmented IDHP by 30%. 10.
      During the course of cellular differentiation induced by dibutyryl cyclic AMP,
      IDHP appeared earlier than I omega CgTX. 11. These results indicate that two
      classes of Ca2+ channels contribute to the HVA currents of this cell line. The
      DHP-sensitive channel is more apt to generate Ca2+ spikes and Ca2+ plateau
      potentials than the omega CgTX-sensitive channel.

PMID- 1375637
TI  - Cyclic GMP-activated channels of salamander retinal rods: spatial distribution
      and variation of responsiveness.
AB  - 1. Patch-clamp methods were used to investigate the areal density and spatial
      location of cyclic GMP-activated channels in the surface membrane of salamander
      rod outer segments. 2. The density of active channels (i.e. channels able to
      respond to cyclic GMP) in patches excised from outer segments was determined from
      the number of active channels, N, and the membrane area, A. N was estimated from
      the current induced by a saturating concentration of cyclic GMP, while A was
      estimated from the electrical capacitance of the patch. 3. In patches excised
      from forty-one isolated outer segments prepared in the light the active channel
      density varied over a remarkable range: 0.34-629 microns-2, with a mean of 166
      microns-2. Density was not correlated with patch area in this or any of the
      conditions studied. 4. The spatial distribution of open channels on the outer
      segment of a transducing rod was measured by recording the local dark current at
      various positions with a loose-patch electrode. The apparent density of open
      channels varied by only about +/- 50% around the circumference of the outer
      segment and up and down its length. This indicates that the wide range of
      densities in excised patches did not result from sampling a non-uniform spatial
      distribution of channels. 5. Patches excised from sixteen dark-adapted whole
      cells with healthy appearances and saturating light responses of normal size had
      active channel densities of 1.1-200 microns-2, with a mean of 60 microns-2.
      Patches from twenty light-adapted whole cells had similar densities. Many
      densities from the whole cells were much lower than expected. This, and the wide
      variation in densities, suggests that obtaining a patch often lowered the density
      of active channels. The number of channels in a patch was quite stable from 1 s
      to 30 min after excision, ruling out progressive denaturation or adsorption of
      channels to the glass as a cause for this effect. 6. The mean active channel
      density in patches excised from whole cells was lower with calcium present in the
      external solution than with calcium absent (80 vs. 152 microns-2, n = 36 and 30
      respectively). 7. We conclude that copies of the channel protein were present at
      a density of at least 650 microns-2 in the surface membrane of the outer segment
      and that the distribution of channels was fairly uniform on a 1 micron
      scale.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375633
TI  - Stimulus-secretion coupling: cytoplasmic calcium signals and the control of ion
      channels in exocrine acinar cells.

PMID- 1375636
TI  - 5-HT3 receptor channels in dissociated rat superior cervical ganglion neurons.
AB  - 1. Whole-cell and single-channel voltage-clamp techniques were used to record the
      5-HT3 receptor-mediated currents in neurons freshly dissociated from rat superior
      cervical ganglia. 2. Whole-cell currents elicited by brief pressure ejection of 5
      HT (10 microM) reversed at -4.5 mV when extracellular and intracellular solutions
      mainly contained NaCl and CsCl. The peak current-voltage relation showed modest
      inward rectification that was fully developed within less than 2 ms of the
      applied voltage step. 3. With prolonged application of 5-HT (10 microM) using a
      fast perfusion system, the response desensitized in two phases with fast and slow
      time constants of 0.57 and 6.0 s at -74 mV. The time constants showed little
      voltage dependence; however, the relative amplitude of the two components was
      significantly dependent on voltage. The time course of desensitization was not
      affected by agents that increase the levels of intracellular cyclic AMP. 4. The
      relative permeability of the channel was determined from reversal potential
      changes. The channel passed small cations non-selectively, with permeability
      ratios (PX/PNa) of 0.93 and 1.24 for Cs+ and K+. The organic cations Tris and
      glucosamine were measurably permeant with permeability ratios of 0.19 and 0.06.
      Ca2+ was fairly permeant with a relative permeability of 0.55 in 20 mM solution
      and of 0.16 when the concentration of CaCl2 was increased to 115 mM. No
      permeability was detected for Cl-. 5. Fluctuation analysis of the whole-cell
      current revealed an apparent single-channel current of approximately 0.18 pA at 
      74 mV. 6. 5-HT-activated single-channel currents were recorded in excised outside
      out patches. When 5-HT (10 microM) was delivered by pressure ejection, channel
      openings appeared rapidly with a delay of 28 ms. The unitary current was about
      approximately 0.80 pA at -74 mV. The channel activity induced by bath perfusion
      of 5-HT (0.8 microM) was significantly reduced by 100 nM of the 5-HT3 receptor
      specific antagonists 3-tropanyl-3,5-dichlorobenzoate (MDL 72222) or 3-tropanyl
      indole-3-carboxylate (ICS 205-930). 7. The single-channel current-voltage
      relation was non-linear, with moderate inward rectification similar to that of
      the whole-cell current. The chord conductance of the channel decreased with
      membrane depolarization from 14.6 pS at -104 mV to only 9.9 pS at -54 mV. Open
      time distributions consisted of two components with mean time constants of 0.45
      and 2.8 ms at -104 mV. Burst-length distributions were also made up of two
      components with time constants of 0.45 and 4.6 ms.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1375638
TI  - Arachidonic acid and prostaglandin E2 activate small-conductance Cl- channels in
      the basolateral membrane of rabbit parietal cells.
AB  - 1. Cl- channels in the basolateral membrane of non-stimulated parietal cells in
      isolated rabbit gastric glands were studied by patch-clamp and noise analysis
      techniques. 2. Voltage-independent whole-cell currents were recorded from
      parietal cells equilibrated with Cl(-)-containing solutions. Upon reducing the Cl
      concentration of the basolateral bathing solution, the current-voltage curve was
      rapidly shifted to the right. The reversal potential changed according to changes
      in the equilibrium potential for Cl-. 3. A Cl- channel blocker, 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB) inhibited whole-cell Cl- currents. The half
      maximal inhibitory concentration of NPPB was 300 microM, and the inhibition was
      reversible (at less than or equal to 200 microM). Another Cl- channel blocker, 4
      acetamido-4'-isothiocyanatostilbene-2,2'-dilsulphonic acid or diphenylamine-2
      carboxylate was much less effective. 4. The power spectra of whole-cell Cl-
      current fluctuations contained one Lorentzian component. The single Cl- channel
      conductance was estimated to be 0.35 pS by the variance noise analysis, which is
      in agreement with the value obtained by a method of power spectrum analysis (0.29
      pS). 5. The addition of arachidonic acid (10 microM) to the basolateral medium
      markedly increased the whole-cell Cl- current. The combined application of a
      cyclo-oxygenase inhibitor, indomethacin (50 microM), and a lipoxygenase
      inhibitor, esculetin (100 microM), increased the Cl- current, whereas the
      administration of a phospholipase A2 inhibitor, mepacrine (100 microM),
      significantly decreased the whole-cell Cl- current. 6. A sizeable increase in the
      whole-cell Cl- current was also induced by a metabolite of arachidonic acid,
      prostaglandin E2 (10 microM), but not by leukotriene B4 (5 microM) or D4 (10
      microM). 7. The present study has shown that small-conductance Cl- channels are
      present in the basolateral membrane of rabbit parietal cells, and that the
      channel was functionally regulated by arachidonic acid and prostaglandin E2.

PMID- 1375639
TI  - Effects of alcohols on responses evoked by inositol trisphosphate in Xenopus
      oocytes.
AB  - 1. The effects of ethanol and other alcohols on inositol 1,4,5-trisphosphate
      (InsP3) signalling were studied in Xenopus oocytes by the use of flash photolysis
      of caged InsP3. Calcium liberation induced by InsP3 was monitored by voltage
      clamp recording of Ca(2+)-activated membrane currents, and by fluorescence of the
      Ca2+ indicator Fluo-3. 2. Membrane current and fluorescence Ca2+ signals evoked
      by light flashes giving small responses were initially potentiated by bath
      application of ethanol (80-400 mM). However, the responses subsequently declined
      while ethanol was present and were strongly reduced or suppressed when it was
      removed. 3. These effects did not arise artifactually from changes in photolysis
      of caged InsP3, as similar results were seen with responses evoked by
      intracellular injections of InsP3. Also, the effects on the membrane current did
      not arise primarily through actions on the Ca(2+)-dependent Cl- channels, since
      currents evoked by intracellular injections of Ca2+ were little changed by
      ethanol. 4. Ethanol reduced the threshold level of InsP3 required to cause Ca2+
      liberation. Thus, potentiation was most prominent with small responses evoked by
      brief light flashes, whereas the predominant effect on larger responses was
      inhibitory. 5. The facilitatory and inhibitory actions of ethanol persisted after
      removing extracellular Ca2+. 6. Intracellular injections of ethanol produced an
      initial inhibition of InsP3 responses, followed, in some oocytes, by a
      potentiation. 7. Methanol had little effect on InsP3 responses, whereas butanol
      and other long-chain alcohols produced strong inhibition, but little or no
      potentiation. 8. We conclude that extracellular application of ethanol produces a
      rapid potentiation of InsP3-mediated Ca2+ liberation, and a more slowly
      developing inhibition. The potentiation may arise through stimulation of InsP3
      formation at the plasma membrane, whereas the inhibition occurs more deeply in
      the cell. Both actions were evident at relatively low concentrations (a few tens
      of millimoles per litre), and might thus be important in the behavioural effects
      of ethanol intoxication.

PMID- 1375640
TI  - Characterization of large-conductance chloride channels in rabbit colonic smooth
      muscle.
AB  - 1. A large-conductance Cl- channel was characterized in cell-free membrane
      patches from the rabbit longitudinal colonic smooth muscle using the patch clamp
      technique. In addition, the regulation of these channels by neurokinin-1 (NK-1)
      receptor agonists and G proteins was studied. 2. No spontaneous channel activity
      was observed in cell-attached patches at the cell resting potential, or in
      excised patches at pipette potentials (Vp) between -20 and 20 mV. In excised
      patches, channel activity could be induced in thirty-six out of ninety-six
      patches by holding the patch at Vp values more negative than -60 mV or more
      positive than 60 mV. Once induced, the channel showed a bell-shaped voltage
      activation curve in high symmetric [Cl-], with maximal open probability between
      20 and -5 mV. Varying cytosolic calcium concentration ([Ca2+]) between 5 x 10(-8)
      M and 1.0 mM had no effect on the voltage activation of the channel. 3. In inside
      out and outside-out patches, when pipette and bath solutions contained equal [Cl
      ] (130 mM), the anion channel showed a linear current-voltage (I-V) relationship
      between -60 and 60 mV with a slope conductance of 309 +/- 20 pS (n = 13).
      Reversal potential measurements indicated that the channel was selective for Cl-
      over Na+ and K+ (PCl/PNa = 6:1). 4. Channel openings from the closed state to the
      full open state as well as transitions through smaller conductance states were
      observed. The smallest detectable substate had a conductance of 15.6 pS. Based on
      the similarities in selectivity and linearity of the I-V curve of the smaller
      conductances with the full open state, and kinetic analysis of channel activity,
      it is concluded that the large conductance channel is composed of multiple
      substates which can either open and close independently, or simultaneously via a
      main gate. 5. The stilbene derivative diiso-thiocyanato-stilbene-disulphonic acid
      (DIDS) and the diphenylamine-2-carboxylate analogue 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB) caused a dose-dependent, reversible flicker
      block of the small conductance and significantly reduced the macroscopic current
      flow through the channel. 6. In quiescent outside-out patches, when the pipette
      contained a 140 mM-CsCl solution with 10(-6) M-CaCl2, 1.2 mM-MgCl2 and 1 mM-GTP,
      and the bath contained Ringer solution, addition of the NK-1 receptor antagonists
      substance P methylester resulted in activation of the full conductance state and
      of smaller substates.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375642
TI  - Flow cytometer analysis of oral premalignant lesions: a pilot study and review.
AB  - In a retrospective study, we examined 34 premalignant lesions of the oral cavity
      by flow cytometer analysis on formalin-fixed, paraffin-embedded tissue submitted
      to the University of Tennessee, Memphis, Oral Pathology Laboratory. Three
      categories of oral epithelial dysplasia were represented (eight mild, seven
      moderate, nine severe), as well as five epithelial hyperplasias without dysplasia
      and five fibrous nodules as controls. The DNA index and total proliferative index
      of each case were calculated. The objective of the study was to determine the
      amount of epithelial dysplasia necessary in oral lesions before DNA aneuploidy or
      high proliferative index is detectable and thus determine if flow cytometric
      analysis can be a diagnostic adjunct for oral premalignant lesions. The results
      showed that some cases in both the control and dysplastic categories exhibited a
      high total proliferative index (control = 1, no dysplasia = 1, mild dysplasia =
      3, moderate dysplasia = 2, severe dysplasia = 2), whereas only the dysplastic
      lesions had an abnormal DNA index [8 of 24 (33%)]. The results indicate that flow
      cytometric analysis may have some limited potential as a diagnostic adjunct in
      oral premalignant lesions.

PMID- 1375643
TI  - Preservation of keratin expression in oral mucosa using a novel transport medium.
AB  - Cellular expression of keratins (intermediate filaments) can be demonstrated by
      immunocytochemistry using unfixed tissue. However, for practical reasons,
      provision of fresh tissue to the laboratory is often difficult. Recently a fresh
      tissue transport medium (Patent applied for) has been developed which allows
      keratin immunocytochemistry to be performed up to 4 days after biopsy. In this
      study oral mucosal biopsies from 10 patients were hemisected, half placed in the
      new transport medium at 4 degrees C and the other half immediately frozen in
      liquid nitrogen. After 4 days frozen sections of both halves of the biopsies were
      stained by immunocytochemistry using various antikeratin antibodies. The
      morphology and staining characteristics of the two halves of the biopsies were
      then assessed. No significant difference could be found in either morphology or
      preservation of keratin expression in specimens stored in transport medium, as
      compared to those in liquid nitrogen. This new transport medium may offer
      considerable advantage for the provision of a histologic and immunocytochemical
      diagnostic service.

PMID- 1375641
TI  - Two types of steady-state desensitization of N-methyl-D-aspartate receptor in
      isolated hippocampal neurones of rat.
AB  - 1. Whole-cell voltage-clamp recordings were made from rat isolated hippocampal
      neurones. Aspartate (Asp) and/or glycine (Gly) were applied by a method in which
      the external solution could be changed within 30 ms and thereafter held constant.
      2. Asp and Gly applied together at maximal concentrations (5 mM and 10 microM,
      respectively) evoked an inward current due to activation of N-methyl-D-aspartate
      (NMDA) receptors. The current peaked and then declined to a steady state during
      the application. The time constant of desensitization (tau) was about 1 s when
      the agonists were applied soon after the onset of whole-cell recording. The
      desensitization became more rapid (tau = 0.3 s) and more complete during the
      first 15 min of recording, and thereafter remained stable; the amplitude of the
      peak response did not change throughout. In solutions containing 10 microM-Gly,
      Asp had an apparent Kd of 51 microM at the peak of response and 20 microM
      measured at the steady state. The steady-state current was 14% of the peak
      current. 3. Asp was applied after a conditioning exposure of the cell of Gly
      (from 1 to 50 microM), together with the same Gly concentration. The maximum
      current evoked by the application of Asp was increased while increasing Gly in
      the conditioning solution, with no change in the apparent Kd for Asp at the peak
      of Asp-activated response. 4. Various concentrations of Asp (plus 10 microM-Gly)
      were applied after a conditioning exposure to Asp (which alone was without
      effect). The maximum current induced by Asp applications was only 28% of that
      observed without conditioning Asp application, but the apparent Kd was unchanged
      (about 57 microM). 5. Test solution containing maximal concentrations of Asp and
      Gly was applied after conditioning exposure to both Asp (varying concentrations)
      and Gly (10 microM). Complete desensitization was caused by 200 microM-Asp. The
      apparent Kd for Asp to induce desensitization (8.7 microM) was less than the Kd
      as an agonist (51 microM). 6. Test solution containing maximal concentrations of
      Asp and Gly was applied after conditioning exposure to both Gly (varying
      concentrations) and Asp (5 mM). Complete desensitization was caused by 1 microM
      Gly. The apparent Kd for Gly to induce desensitization (120 nM) was less than the
      Kd as a co-agonist (about 1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375644
TI  - Cytokeratins as epithelial differentiation markers in premalignant and malignant
      oral lesions.
AB  - The keratin expression pattern in oral stratified epithelium is related to the
      cellular differentiation level. The normal pattern shows the keratin pair K5 and
      K14 in the stratum basale whereas K1 and K10, or K4 and K13, are the two pairs
      associated with differentiating suprabasal cells. Monoclonal and polyclonal
      antibodies to individual keratins (K10, K13 and K14) were used in a two-color
      immunofluorescence staining method to study their coexpression in single cells.
      Altered keratin expression in premalignant and malignant lesions indicated
      abnormal differentiation. Monospecific keratin antibodies were suggested to be
      useful for evaluation of epithelial differentiation changes in oral dysplasias
      and oral squamous cell carcinomas.

PMID- 1375645
TI  - Two forms of decidualization-associated protein and their physicochemical
      relationship with acute-phase alphamacrofetoprotein in rats.
AB  - After isolation and purification, rat acute-phase protein, alphamacrofetoprotein
      and the uterine decidual protein, decidualization-associated protein were
      compared. They are similar in molecular weight and amino acid composition, and
      behave similarly during native polyacrylamide gel electrophoresis and are
      crossreactive with polyclonal antisera. They differ in pI values: with a mean pI
      of 4.83 for alphamacrofetoprotein, 5.16 for the major form of decidualization
      associated protein and 4.97 for the remainder. Alphamacrofetoprotein and
      decidualization-associated protein differ in carbohydrate content and subunit
      structure, but show similar susceptibility to trypsin digestion. Evidence is
      provided that both the decidual species form complexes with proteases and that
      these are present in the extracted decidual proteins. The distribution of the
      forms of decidualization-associated protein in the tissues during pregnancy and
      parturition is described and discussed.

PMID- 1375646
TI  - Percutaneous, ultrasound-directed ablation of ectopic pregnancy with
      methotrexate. A report of three cases.
AB  - The early diagnosis of unruptured ectopic pregnancy has been facilitated by the
      availability of high-resolution ultrasound and sensitive quantitative assays for
      beta-human chorionic gonadotropin. Nonsurgical treatment of selected patients has
      been advocated. Three patients with fairly advanced unruptured ectopic
      pregnancies were treated with ablation with methotrexate using an ultrasound
      directed, percutaneous technique. That approach appears to be reasonable and safe
      in selected patients, though the subsequent reproductive performance is unknown.

PMID- 1375647
TI  - Immunoregulatory effects of Borrelia burgdorferi on T-B cell interactions.
AB  - Late stages of Lyme borreliosis are characterized by a disproportionate
      inflammatory response presumably elicited by only minute amounts of persisting
      antigen. To explore the possibility that amplification mechanisms of the immune
      response shape disease manifestations, we studied immunoregulatory properties of
      Borrelia burgdorferi antigens and analyzed whether they influence B cell-T cell
      cooperation. B. burgdorferi was found to induce peripheral resting B cells to
      function as effective antigen presenting cells for B. burgdorferi sonicate (Bb)
      and unrelated third party antigens. Morphologically and phenotypically, pulsed B
      cells represented small resting B cells and did not acquire activation markers.
      These data suggest that distinct antigen-presenting cells are involved in B.
      burgdorferi induced immune responses. B lymphocytes may play a crucial role in
      amplifying T cell responses, especially by recruiting antigen specific and
      nonspecific T cells to regions where minute amounts of spirochetal antigens are
      present.

PMID- 1375648
TI  - Effect of topical capsaicin in the therapy of painful osteoarthritis of the
      hands.
AB  - Topical capsaicin 0.075% was evaluated for the treatment of the painful joints of
      rheumatoid arthritis (RA) and osteoarthritis (OA) in a 4 week double blind,
      placebo controlled randomized trial. Twenty-one patients were selected, all of
      whom had either RA (n = 7) or OA (n = 14) with painful involvement of the hands.
      Assessments of pain (visual analog scale), functional capacity, morning
      stiffness, grip strength, joint swelling and tenderness (dolorimeter) were
      performed before randomization. Treatment was applied to each painful hand joint
      4 times daily with reassessment at 1, 2 and 4 weeks after entry. One subject did
      not complete the study. Capsaicin reduced tenderness (p less than 0.02) and pain
      (p less than 0.02) associated with OA, but not RA as compared with placebo. A
      local burning sensation was the only adverse effect noted. These findings suggest
      that topical capsaicin is a safe and potentially useful drug for the treatment of
      painful OA of the hands.

PMID- 1375649
TI  - Evaluation and management of pain in children with juvenile rheumatoid arthritis.
AB  - The systematic evaluation and management of chronic and recurrent pain in
      children with juvenile rheumatoid arthritis (JRA) is only in the beginning stages
      of empirical development. While recent advances have been made in the assessment
      of pain secondary to JRA, very little clinical research has been targeted toward
      pain management. Development of reliable and valid pediatric pain measures is the
      first step in advocating controlled clinical trials with pain as an essential
      outcome variable.

PMID- 1375650
TI  - Properties of single- and double-barreled Cl channels of shark rectal gland in
      planar bilayers.
AB  - Chloride channels from the apical plasma membrane fraction of rectal gland of
      Squalus acanthias were characterized by incorporation into planar bilayers in the
      presence of cAMP-PK/ATP. In a total of 80 bilayer preparations, 21 Cl-selective
      channels were observed as single channels and 13 as pairs. This was a
      significantly greater number of double Cl channels than expected from a binomial
      distribution. The double Cl channels were divided into two groups based on
      kinetic and voltage-dependent behavior. One group had properties identical to the
      single channels (gb1) while the other was consistent with a double-barreled
      channel (gb2) with coordinated activity between proto-channels. The single
      channel slope conductances of gb1 and gb2 from -60 to +20 mV with a 250/70 mM KCl
      gradient were 41 and 75 pS, respectively. With symmetrical 250 mM KCl, the I-V
      relation of gb1 showed outward rectification with 47.8 +/- 6.6 pS at cis negative
      potentials and 68.9 +/- 6.1 pS at cis positive potentials. gb1 was open from 70
      to 95% at all electrochemical potentials from -80 to +40 mV. gb2 was steeply
      voltage dependent between -80 and -20 mV. Both gb1 and gb2 were insensitive to Ca
      (from 100 nm to 1 microM), blocked by 0.1 mM DIDS and highly selective for
      chloride. These data suggest that double-barreled Cl channels are related to the
      family of small, outwardly rectifying Cl channels of epithelial membranes.

PMID- 1375651
TI  - Phosphorylation modulates the voltage dependence of channels reconstituted from
      the major intrinsic protein of lens fiber membranes.
AB  - Major intrinsic polypeptide (MIP), a 28-kDa protein isolated from lens fiber cell
      membranes, forms large, nonselective channels when reconstituted into lipid
      bilayers. MIP channels are regulated by voltage, such that these channels close
      when the potential across the membrane is greater than 30 mV. We have
      investigated the modulation of the voltage-dependent closure of MIP channels by
      phosphorylation. In this report, we describe the isolation of two isomers of MIP
      from lens fiber cell membranes. These isomers differ by a single phosphate at a
      protein kinase A phosphorylation site. The phosphorylated isomer produces
      channels that close in response to applied voltages when reconstituted into
      bilayers. The nonphosphorylated isomer produces voltage-independent channels.
      Direct phosphorylation with protein kinase A converts voltage-independent
      channels to voltage-dependent channels in situ. Analyses of macroscopic and
      single-channel currents suggest that phosphorylation increases the voltage
      dependent closure of MIP channels by increasing closed channel lifetimes and the
      rate of channel closure following the application of voltage.

PMID- 1375652
TI  - Ion channel enzyme in an oscillating electric field.
AB  - To explain the electrical activation of several membrane ATPases, an
      electroconformational coupling (ECC) model has previously been proposed. The
      model explained many features of experimental data but failed to reproduce a
      window of the field intensity for the stimulated activity. It is shown here that
      if the affinities of the ion for the two conformational states of the transporter
      (one with binding site on the left side and the other on the right side of the
      membrane) are dependent on the electric field, the field-dependent transport can
      exhibit the observed window. The transporter may be described as a channel enzyme
      which opens to one side of the membrane at a time. It retains the energy
      transducing ability of the earlier ECC models. Analysis of the channel enzyme in
      terms of the Michaelis-Menten kinetics has been done. The model reproduced the
      amplitude window for the electric field-induced cation pumping by (Na,K)-ATPase.

PMID- 1375653
TI  - Influence of codon context on UGA suppression and readthrough.
AB  - We studied the influence of the codon context on UGA suppression by a suppressor
      tRNA and on UGA readthrough by a normal tRNA in Escherichia coli. This was done
      by a series of constructs where only the immediate context of the TGA codon was
      varied by only one nucleotide at a time. For both UGA suppression and UGA
      readthrough the codon context had a similar influence according to the following
      rules. (1) The nature of the nucleotide immediately adjacent to the 3' side of
      the UGA is an important determinant; at that position the level of UGA
      translation is influenced by the nucleotides in the order A greater than G
      greater than C greater than U. (2) At extremely high or low levels of UGA
      translation this influence of the adjacent 3' nucleotide is not seen. (3) In all
      cases, the nature of both the nucleotide immediately adjacent to the 5' side of
      the codon and that following the base adjacent to the 3' side of the codon have
      little effect, if any, on UGA translation. The varying influence of the codon
      context effect on UGA translation is discussed in relation to its role in gene
      expression.

PMID- 1375654
TI  - Temperature dependence of the kinetics of the urea-induced dissociation of human
      plasma alpha 2-macroglobulin into half-molecules. A minimum rate at 15 degrees C
      indicates hydrophobic interaction between the subunits.
AB  - The kinetics of the urea-induced dissociation of human plasma alpha 2
      macroglobulin to half-molecules has been studied as a function of temperature by
      using small-angle scattering of X-rays and neutrons. The most striking result of
      the present investigation is that there is a minimum in reaction rate at about 15
      degrees C, and that the rate increases when the temperature is lowered, or
      raised, from that value. By analyzing the first-order rate constants in terms of
      transition-state theory it was found that the dissociation is associated with a
      large and positive change in heat capacity between the activated complex and
      native alpha 2-macroglobulin (delta CP is in the range 5 to 6 kJ mol-1 K-1). In
      analogy with pure thermodynamic investigations, where a large change in heat
      capacity normally is interpreted as a melting of hydrophobic interaction, we
      therefore propose that hydrophobic interaction is involved in the so-called non
      covalent interactions between the subunits of alpha 2-macroglobulin. As a result
      of the present investigation, it also follows that the free energy of activation
      delta G has a maximum at about 32 degrees C, whereas the enthalpy of activation
      delta H and the entropy of activation delta S are zero at about 15 degrees C and
      32 degrees C, respectively. These temperatures are slightly dependent upon the
      concentration of urea and upon whether the reaction is run in a 1H or a 2H
      medium. Furthermore, from the kinetic point of view, at low temperature the
      reaction can be characterized as enthalpy driven, whereas at high temperature, it
      can be characterized as entropy driven.

PMID- 1375655
TI  - Overproduction of nitric oxide in cytokine-mediated and septic shock.

PMID- 1375656
TI  - Increased circulating nitrogen oxides after human tumor immunotherapy:
      correlation with toxic hemodynamic changes.
AB  - BACKGROUND: Toxicity to interleukin-2 (IL-2) tumor immunotherapy is manifested
      principally by the vascular leak syndrome, hypotension, and a hyperdynamic
      response with low systemic vascular resistance. Nitric oxide (.N = O), a recently
      discovered biological mediator of vascular smooth muscle relaxation, is produced
      in increased amounts by numerous cell types exposed to a number of inflammatory
      cytokines. PURPOSE: Our purpose was to determine if there is an increased
      production of .N = O in patients receiving IL-2 tumor immunotherapy, and, if so,
      whether increases in .N = O production correlate with hemodynamic instability.
      METHODS: Twelve patients undergoing immunotherapy trials with IL-2 and anti-CD3
      monoclonal antibody-activated lymphocytes (T-AK cells) were studied. Plasma
      levels of nitrate (NO3-), the stable end metabolic product of .N = O synthesis,
      were measured before and at the end of IL-2 treatment cycles. RESULTS: We
      observed a ninefold increase in plasma levels of NO3- in patients after 7 days of
      treatment (P less than .0001). A significant decrease in both systolic and
      diastolic blood pressures was observed in all patients (P less than .001).
      CONCLUSIONS: We propose that mediated induction of .N = O synthase enzyme leads
      to progressive increases in .N = O production which, in turn, produces clinically
      significant hypotension. IMPLICATIONS: Since .N = O synthesis can be
      competitively inhibited by L-arginine analogues, a possible pharmacologic
      modulation of .N = O production could potentially contribute to better management
      of toxic side effects seen in IL-2 cancer therapies.

PMID- 1375657
TI  - Favorable long-term survival following induction chemotherapy with cisplatin,
      fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally
      advanced head and neck cancer.
AB  - BACKGROUND: The majority of patients with head and neck cancer die of
      locoregional recurrence of disease following surgery and/or radiotherapy.
      PURPOSE: Our purpose was to administer induction chemotherapy, perform surgery,
      and administer concomitant chemoradiotherapy in rapid sequence and to evaluate
      their impact on locoregional and distant tumor control. METHODS: Sixty-four
      patients with previously untreated, locoregionally advanced head and neck cancer
      received two cycles of cisplatin, bleomycin, and methotrexate (PBM) (33 patients)
      or cisplatin, fluorouracil (5-FU), and leucovorin (PFL) (31 patients). PFL was
      given to patients who were unable to receive bleomycin. Local therapy consisted
      of surgery and/or concomitant chemoradiotherapy with 5-FU, hydroxyurea,
      leucovorin, and radiotherapy (FHX-L), all administered every other week. RESULTS:
      Complete and overall induction response rates were 21% and 79%, respectively, for
      PBM and 29% and 81%, respectively, for PFL. At completion of local therapy, 81%
      of the patients were disease-free. With a median follow-up of 35 months, the
      median survival and time to progression are 22 and 17 months, respectively, for
      PBM and have not been reached for PFL. Locoregional recurrence of disease is 30%
      for PBM and 26% for PFL. Distant disease progression is 24% for PBM and only 3%
      for PFL. CONCLUSIONS: The sequencing of induction chemotherapy and concomitant
      chemoradiotherapy is feasible and results in a high local control rate and in an
      encouraging survival rate with PFL. The high distant failure (i.e., outside the
      head and neck area) rate of PBM suggests insufficient systemic activity for that
      regimen. IMPLICATIONS: Concomitant FHX-L chemoradiotherapy may improve regional
      control rates of advanced head and neck cancer. Effective systemic therapy may be
      needed to control systemic micrometastases. PFL, but not PBM, appears to be
      suitable to accomplish that goal.

PMID- 1375659
TI  - The safety, efficacy and compliance of terazosin therapy for benign prostatic
      hyperplasia.
AB  - The primary objective of the present interim analysis of an open label study
      initiated in December 1988 is to provide further insight into the long-term
      safety, efficacy and compliance of terazosin, a long-acting selective alpha 1
      blocker, for the treatment of symptomatic benign prostatic hyperplasia (BPH). A
      total of 45 normotensive patients with symptomatic BPH was enrolled into this
      study. The dose of terazosin was titrated to 5 mg. during a 1-month period
      provided adverse reactions and orthostatic hypotension were not observed. The
      subjects were maintained on 5 mg. terazosin throughout the 24-month followup. The
      peak and mean urinary flow rates, obstructive and irritative Boyarsky symptom
      scores, and systolic and diastolic blood pressures were evaluated at 2, 6, 12, 18
      and 24 months after initiation of therapy. Of the 45 subjects 21 (47%) exhibited
      a durable clinical response with no significant adverse events during the 24
      month followup. The obstructive and irritative symptom scores decreased by 63%
      and 35%, respectively, after 2 months of terazosin therapy. These improvements in
      obstructive and irritative symptom scores were maintained throughout the 2-year
      followup. The peak and mean urinary flow rates improved by 42% and 48%,
      respectively, after 2 months of terazosin therapy. The changes in mean urinary
      flow rate increased, whereas the changes in peak urinary flow rate decreased
      during followup. Of the patients 6 (13%) were withdrawn from the study due to an
      adverse event. Our study demonstrates the safety, efficacy and compliance of
      terazosin therapy for BPH during a 2-year followup.

PMID- 1375658
TI  - Influence of aminoglycoside antibiotics, streptomycin and kanamycin on histamine
      secretion in mast cells.
AB  - Effects of kanamycin and streptomycin on histamine release from rat mast cells
      were examined in response of the cells to concanavalin A(Con A) plus
      phosphatidylserine (PS), phytohemagglutinin (PHA) plus PS or a mixture of low
      molecular-weight polymers of P-methoxy-N-methylphenethylamine (compound 48/80).
      In the response to each of the above stimuli, kanamycin (20 mM) or streptomycin
      (20 mM) caused a decrease in the histamine release elicited in the presence of
      extracellular Ca2+ (1 mM), although streptomycin showed the much higher
      inhibitory potency than kanamycin. Similarly, streptomycin was much more
      effective in suppressing compound 48/80-triggered histamine release in the
      absence of external Ca2+. Histamine release in the absence of external Ca2+ in
      the response to the lectin plus PS diminished with increasing concentration of
      kanamycin, and in this respect streptomycin was much less effective. In the
      response to the lectin plus PS, external Ca2+ possessed potency to antagonize
      kanamycin (10 mM)- or streptomycin (10 mM)-caused inhibition of the histamine
      release, although more markedly the kanamycin-caused one. Streptomycin and
      kanamycin inhibit histamine release from mast cells challenged with IgE-directed
      secretagogue or compound 48/80, and the responsible mechanisms seem to implicate
      the Ca(2+)-antagonistic action on the stimulus-provoked influx of Ca2+ and
      impairment of the cellular events linked to exocytosis.

PMID- 1375660
TI  - Transurethral hyperthermia for benign prostatic hyperplasia patients with
      retention.
AB  - From 1989 to 1990, 32 poor surgical risk patients with urinary retention were
      treated with transurethral microwave hyperthermia at the department of urology,
      University of Leuven in Belgium. Mean patient age was 73 years (range 58 to 90
      years) and mean duration of retention was 4 weeks (range 3 to 12 weeks). Followup
      ranged from 13 to 82 weeks, with a mean of 31 weeks. Bilobar or trilobar
      hyperplasia was diagnosed in 25 patients (78%), while 7 (22%) had median lobe or
      median bar hypertrophy. The mean prostatic volume was 52 cc (range 25 to 150 cc).
      Transurethral microwave hyperthermia was given with a helical antenna at 915 MHz.
      once or twice per week. The mean number of transurethral microwave hyperthermia
      sessions was 8.9 (range 5 to 10). Each session consisted of a 60-minute treatment
      at a mean maximum temperature of 45.4C (range 43.7 to 47.2C), average temperature
      43.9C (range 42.7 to 45.5C) and minimum temperature 42.0C (range 40.2 to 43.0C).
      The temperature was continuously monitored, including thermal mapping in all
      patients. Of the 25 patients who presented with bilobar or trilobar hyperplasia
      18 (72%) were catheter-free for the duration of followup. Of the 7 median lobe or
      median bar patients 1 (14%) showed sufficient improvement to warrant catheter
      removal. This patient, however, had recurrent retention 4 months after
      transurethral microwave hyperthermia. In patients with bilobar and trilobar
      hyperplasia a strong correlation was observed among maximum temperature (p =
      0.0006), average temperature (p = 0.0033) and treatment response. As expected, no
      such correlation existed between minimum temperature and response to treatment (p
      = 0.56). Our study has again demonstrated therapeutic activity in patients with
      benign prostatic hyperplasia treated with transurethral microwave hyperthermia. A
      new finding was a strong correlation between temperature and response.

PMID- 1375661
TI  - Prostatic and periprostatic interstitial temperature measurements in patients
      treated with transrectal thermal therapy (local intracavitary microwave
      hyperthermia).
AB  - One of the questions raised regarding the use of transrectal thermal therapy in
      the treatment of benign prostatic hyperplasia (BPH) is whether there is a uniform
      and safe temperature distribution within the prostate. Our study represents the
      first attempt in humans to map the interstitial thermal distribution in the
      prostate during transrectal thermal therapy. With the patient under local
      anesthesia and under ultrasound guidance, a transperineal 3-point thermocouple
      was placed into various areas of the prostate in 15 patients. Prostatic-urethral
      thermocouple distance ranged from 1 to 3 cm. A urethral catheter containing a 5
      point linear array thermocouple was placed and the balloon was inflated so that
      the proximal point was at the bladder neck and the remaining points were at 1 cm.
      intervals along the prostatic urethra. Power (25 watts) was delivered via the
      Primus (Technomatix) transrectal microwave applicator with simultaneous cooling
      of the rectal mucosa (between 12 and 14C). Treatment was delivered for 60 minutes
      and temperatures were recorded. In the prostatic substance a maximal temperature
      of 45C was observed during the heat-up phase and this decreased as the vasoactive
      response occurred. Temperature along the prostatic urethra varied between 40 and
      43C and never exceeded 44C. A similar distribution of temperature was registered
      in the thermocouple points in the prostatic substance. The anticipated thermal
      dose of 41.5 +/- 1C for 60 minutes was achieved in the prostatic substance as
      measured by the sensors in the prostatic urethra and interstitial sensors. The
      results suggest that transrectal thermal therapy delivers a uniform and safe
      distribution of heat in the prostatic substance and urethra. Clinical trials are
      currently underway to ascertain the efficacy of transrectal thermal therapy in
      the management of BPH.

PMID- 1375662
TI  - Mortality, morbidity and complications following transurethral resection of the
      prostate for benign prostatic hypertrophy.
AB  - A total of 388 men undergoing transurethral resection of the prostate for benign
      prostatic hypertrophy during 1988 entered a prospective cohort study designed to
      examine the outcome of surgery during postoperative year 1. Self-administered
      questionnaires were completed preoperatively, and at 3, 6 and 12 months
      postoperatively. The surgeons completed 1 questionnaire shortly after surgery and
      another questionnaire 3, 6 or 12 months later. The mortality rate during the 12
      months of followup was 2.8% (11 deaths). The surgeons reported perioperative
      complications in 14% of the patients and immediate postoperative complications,
      excluding urinary tract infections, in 17%. During the first 3 months
      postoperatively 38% of the patients reported incontinence and 25% had a urinary
      tract infection. Between 6 and 12 months postoperatively only 12% of the patients
      were troubled by either condition. The postoperative prevalence of impotence
      (24%) did not alter during followup and was similar to that reported
      preoperatively (22%). Of the patients 74% reported feeling better and 78%
      experienced a decrease in the overall level of symptoms postoperatively. The
      improvement in symptom levels was greatest in those with the most severe
      preoperative symptoms, and obstructive symptoms were alleviated slightly more
      than irritative symptoms.

PMID- 1375664
TI  - Re: A comparison of transurethral and transrectal microwave hyperthermia in poor
      surgical risk benign prostatic hyperplasia patients.

PMID- 1375663
TI  - Pediatric renal transplantation under FK-506 immunosuppression.
AB  - Renal transplantation (11 cadaveric and 1 living-related donor) was performed in
      12 pediatric recipients (mean age 10.8 years) under FK-506 immunosuppression in
      combination with prednisone therapy. At a mean followup of 6.1 months, patient
      and graft survival rates were 100% and 92%, respectively. The only graft loss was
      due to the recurrent hemolytic uremic syndrome 4 days after transplantation. In
      the functioning grafts the mean serum creatinine is 1.59 +/- 1.27 mg./dl. and the
      mean blood urea nitrogen is 36.3 +/- 24.6 mg./dl. Three patients take no
      prednisone, 5 are receiving 0.15 to 0.25 mg./kg. per day and 3 are taking 0.35 to
      0.5 mg./kg. per day. There was a total of 8 rejection episodes in 5 patients. All
      rejection episodes were successfully reversed. Complications of transplantation
      included an episode of seizures in 1 patient, cytomegalovirus infection in 1 and
      steroid-induced diabetes mellitus in 1. Since pediatric transplant recipients are
      a group in whom the reduction or elimination of steroids is highly desirable, FK
      506 immunosuppression may be particularly suited for use in this population.

PMID- 1375665
TI  - Evaluation of plasmatic leucocyte elastase levels in coronary artery disease.
AB  - Leucocyte elastase may be involved in the structural modification observed in the
      atherosclerotic process. Therefore, we tested the usefulness of leucocyte
      elastase plasma level determination as a marker for atherosclerosis. Plasma
      levels of elastase were determined by ELISA in 100 consecutive patients (mean age
      56 +/- 9.8 years) admitted to hospital for coronary angiographic investigation of
      chest pain. Eighty-seven patients had evidence of atherosclerosis, and 13
      patients had normal coronary vessels. No significant difference in leucocyte
      elastase was found between the 2 groups, nor was there any relationship between
      elastase levels and the severity of atherosclerosis. However, relationships
      between plasma leucocyte elastase levels and various lipid fractions (Apo AI,
      LDL) and daily tobacco consumption were found. Leucocyte elastase may thus play a
      role not only by direct modification of the vessel wall, but also indirectly via
      risk factors such as dyslipoproteinemia and leucocyte toxicity.

PMID- 1375666
TI  - [Leukocyte adhesion molecules and their abnormality].
AB  - A brief commentary on leukocyte adhesion molecules, including integrin family,
      immunoglobulin superfamily and selectin or LEC-CAM family is made. A recent
      concept on the molecular mechanisms of the leukocyte adhesion to cell surface is
      also described. An immunodeficiency disease called "leukocyte adhesion deficiency
      (LAD)" that is defective in expression of leukocyte adhesion molecules of
      integrin family, LFA-1, Mac-1 and p150, 95, is discussed with special reference
      to its clinical features, laboratory findings, neutrophil functions, lymphocyte
      functions and molecular defects. Some abnormal expression of a Fc-gamma receptor
      in neutrophils and new data concerning the molecular defects found in Japanese
      patients are also included.

PMID- 1375667
TI  - [In vivo effects on human neutrophils by administration of rhG-CSF and clinical
      significance].
AB  - To evaluate the clinical effect by administration of recombinant human
      granulocyte-stimulating factor (rhG-CSF) post chemotherapy in non-Hodgkin
      malignant lymphoma (NHL), 17 patients with NHL were subjected to this study.
      Administration of rhG-CSF ameliorated the decrease in absolute neutrophil counts
      after the cytotoxic chemotherapies and activated neutrophil functions in active
      oxygen product and expressions of adhesion proteins. To consistent with these
      results, rhG-CSF administrations post cytotoxic chemotherapy were effective for
      reducing infection complications associated with neutropenia. Furthermore,
      administration of rhG-CSF increased peripheral hematopoietic progenitor cells,
      thus suggesting promising therapeutic potential for autografting. Recently, it
      has been reported that blood neutrophils may synthesize mRNA and proteins
      important in inflammation including various cytokines such as IL-1, IL-6, TNF
      alpha and IFN-alpha, but, administration of rhG-CSF showed no obvious effect on
      the level of either IL-1, IL-6, TNF-alpha or IFN-alpha in sera, and furthermore,
      the in vitro stimulation by rhG-CSF induced no significant production of these
      cytokines and expressions of TNF-alpha and IFN-alpha mRNAs. Finally, we studied
      on anti-tumor effect of administration of rhG-CSF in CDF1 mice inoculated with
      syngeneic lymphoma cells. rhG-CSF infusion suppressed the liver metastasis and
      prolonged the overall survival, thus suggesting the hypothesis that use of rhG
      CSF in some patients with NHL might control the disease through stimulating both
      production and functional activation of neutrophils.

PMID- 1375668
TI  - [Progress in hematological malignancy of aged--therapy of malignant lymphoma in
      aged].

PMID- 1375669
TI  - [The use of a metallic stent in 32 patients with benign prostatic hypertrophy.
      Preliminary results and 3 months of follow-up].
AB  - A prospective noncontrolled study of the safety and potential efficacy of the
      metallic stent was performed on 32 patients with benign prostatic hypertrophy.
      Mean age was 76.6 years (range, 56-98 years), and mean prostatic volume was 24.2
      cm3. The patients were selected on the basis of a quantitative symptom score
      (QSS), uroflowmetry measurements, and residual urine volume (RU). Nineteen
      patients had urinary retention and remaining 13 patients had moderate symptoms
      and signs of prostatism. Placing the stent was successfully done in 31 patients
      (97%). It took 15 minutes to place the stent using transabdominal and/or
      endorectal sonography. After 3 months, 27 patients (87%) showed improved QSS. In
      patients with dysuria, maximum flow rate (MFR) and RU before treatment were 6.9
      +/- 1.7 ml/sec and 112.3 +/- 61.8 ml, respectively. After treatment, they
      improved to 12.3 +/- 2.7 ml/sec and 12.7 +/- 6.7 ml, respectively. On the other
      hand, all patients who had urinary retention were able to urinate just after
      treatment, and MFR and RU were 12.9 +/- 3.6 ml/sec and 24.4 +/- 43.3 ml,
      respectively. Evaluation on the basis of improvement in MFR and reduction in RU
      showed that the stent was effective in 71% of total patients (22 out of 31
      patients), 94% of the patients with urinary retention (17 out of 18 patients).
      The overall clinical efficacy of this stent was 68% (21 patients). There were no
      major complications such as urge incontinence and urinary tract infection during
      follow-up. Although proximal migration of the stent was observed in 6 patients,
      the stent could be taken out and replaced in 4 patients. From the above results,
      we conclude that the metallic stent is useful for the treatment of prostatism and
      urinary retention.

PMID- 1375670
TI  - [In-vivo enhancement of neutrophil function by administration of recombinant
      human granulocyte colony-stimulating factor (rhG-CSF) in cyclophosphamide (CPA)
      treated mice].
AB  - The in-vivo effects of recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) on the number and function (phagocytosis and superoxide production) of
      peripheral neutrophils were studied in time sequence in cyclophosphamide (CPA)
      treated mice. The neutrophil function was evaluated by the phagocytosis of
      fluorescent particles, analyzing the number of fluorescence-positive cells and
      the fluorescence intensity of each neutrophil by flow cytometry and also by the
      superoxide production, measuring chemiluminescence of the leukocyte suspension by
      a photometer. In CPA-treated (100 mg/kg) mice, the neutrophil function including
      both the phagocytosis and the superoxide production declined significantly (p
      less than 0.01) as the peripheral neutrophil count (PNC) decreased, reached the
      nadir on the same day as PNC and returned to the normal level 8 days after first
      CPA treated day (day 0). When rhG-CSF (100 micrograms/kg) was administered
      subcutaneously daily for 5 consecutive days initiating at day 1, a decrease in
      PNC and a decline in the neutrophil function were prevented and a significant (p
      less than 0.05-p less than 0.01) increase of PNC was observed after day 4. In
      addition, the function of increased neutrophils was significantly (p less than
      0.05-p less than 0.01) enhanced after day 4 and even at day 3, when an increase
      in PNC was not observed yet. The study shows that rhG-CSF appears to enhance
      neutrophil function by a direct effect on mature neutrophils, which have been
      impaired by CPA at the phase of progenitor cells in the bone marrow and
      subsequently have appeared in the peripheral blood and that rhG-CSF is effective
      on the impaired host defense mechanism in CPA-treated mice, improving not only
      drug-induced neutropenia but also the deteriorated function of neutrophils.

PMID- 1375671
TI  - [The distribution and localization of alpha 1-adrenoceptor agonist on the bladder
      and urethra of female rats].
AB  - The distribution of selective alpha 1-adrenoceptor agonist 1-(2',5'
      dimethoxyphenyl)-2-glycinamidoethanol hydrochloride, midodrine, and its active
      metabolite 1-(2',5'-dimethoxyphenyl)-2-aminoethanol, DMAE, was evaluated on
      bladder and urethra of 8-weeks and 52-weeks old female rats. Prior to the
      intravenous injection of 14C-labeled midodrine and DMAE, bilateral ureters were
      ligated to prevent drug uptake from the urinary tract. In 8-weeks rats, 14C
      midodrine activity was significantly (p less than 0.01) higher in the bladder
      than in the femoral muscle, which served as a control for drug distribution.
      Similarly, higher uptake of 14C-DMAE was observed in the bladder than in the
      femoral muscle (p less than 0.01) and the urethra (p less than 0.05). In 52-weeks
      rats, there was no significant difference of midodrine uptake among these
      tissues. However, significantly higher uptake of 14C-DMAE was observed in the
      urethra than in the femoral muscle (p less than 0.05). Compared with midodrine,
      the concentration of DMAE was significantly increased in the bladder of 8-weeks
      rat and in the urethra of 52-weeks rats (respectively, p less than 0.05). In
      autoradiogram, the grains corresponding to midodrine and DMAE were diffusely
      distributed on the smooth muscles of bladder (mainly bladder neck and trigone)
      and urethra. The grains were also recognized on the vessels and perivascular
      areas of these tissues. These findings support that midodrine and DMAE could be
      effective for stress incontinence, because these drugs are known to bind
      specifically to alpha 1-adrenoceptor.

PMID- 1375672
TI  - Isolation and characterization of cDNA from renal tubular epithelium encoding
      murine Rantes.
AB  - We have been interested in identifying proinflammatory molecules which might play
      a role in attracting monocytes and T cells to the kidney. Some of the new
      intercrines are potential candidates. In this report we have isolated cDNA
      encoding murine Rantes (MuRantes) from renal tubular epithelium (MCT cells).
      MuRantes is a 91 amino acid member of the -C-C- or intercrine beta subgroup of
      the Scy superfamily. The amino acid sequence for mature MuRantes was deduced from
      its coding cDNA and was found to be 90% homologous to its mature human
      counterpart (HuRantes). MCT epithelium expresses a single mRNA transcript for
      MuRantes of approximately 1100 bp. The MuRantes protein could be detected in cell
      lysates of MCT epithelium by western blotting and in the cytoplasm of MCT cells
      by immunofluorescence using a polyclonal antibody generated against HuRantes
      fusion protein. A search protocol using MuRantes-specific primers and cDNA
      amplification revealed that mRNAs for MuRantes are expressed additionally in
      syngeneic mesangial cells (MMC cells), whole kidney, liver, and spleen, as well
      as in nephritogenic antigen-specific CD4+ helper and CD8+ effector T cells. cDNA
      amplification studies also demonstrated a significant elevation in mRNA
      transcripts encoding MuRantes in response to the stimulation of MCT epithelium
      with TNF alpha and IL-1 alpha in culture, but not with TGF beta, gamma IFN, or IL
      6. Our findings indicate that proximal tubular epithelium is an authentic source
      of MuRantes, and that transcripts encoding MuRantes are responsive to the
      modulating influence of paracrine factors having a known role in the development
      of parenchymal injury.

PMID- 1375673
TI  - Cardioplegic arrest of the myocardium with calcium blocking agents.
AB  - This study was designed to compare the effects of the calcium slow channel
      blocking agents verapamil (0.15 mg/kg), diltiazem (0.15 mg/kg), and nifedipine
      (50 micrograms/kg) on the myocardium after global ischemia and reperfusion in the
      in situ canine model. Animals were subjected to 120-min normothermic global
      ischemia, followed by 45-min reperfusion. Cardioplegic arrest of the myocardium
      was achieved by administering one of the three calcium antagonists in a multidose
      fashion. Superior preservation (p less than 0.01) of left ventricular (LV)
      systolic function was achieved in group I (verapamil cardioplegia). dP/dt, at an
      intraventricular balloon volume of 25 cc, was 83% of control after reperfusion in
      group I. Group II (diltiazem) and group III (nifedipine) achieved only 55 and 63%
      of their preischemic dP/dt values. LV chamber stiffness was increased in hearts
      protected with nifedipine. The exponential constant m was increased from 0.04 +/-
      0.01 to 0.08 +/- 0.01. Coronary blood flow after reperfusion increased from 120
      to 184 cc/100 gr/min in group I (p less than 0.01). The hyperemic response in
      group III was negligible. The O2 consumption of the reperfused myocardium was not
      significantly altered in any of the treatment groups. Lactate metabolism during
      ischemia and after reperfusion was similar in all groups. ATP values were
      markedly reduced in all groups (p less than 0.05). Immediately after ischemia,
      ATP was 50, 28, and 44% of control in group I, II, and III, respectively. The
      excellent preservation of systolic function and a physiologic hyperemic response
      by verapamil could not be correlated with improved preservation of high-energy
      compounds or with significant changes in myocardial O2 consumption.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1375674
TI  - Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake
      function in idiopathic dilated cardiomyopathy.
AB  - Desensitization of myocardial beta-adrenergic receptors may result both from an
      impairment of the norepinephrine (NE) neuronal uptake function and from an
      increase in circulating NE concentrations. The respective role of these two
      mechanisms of desensitization was examined in 18 patients with congestive heart
      failure related to an idiopathic dilated cardiomyopathy. The neuronal NE uptake
      system was evaluated by [123I]metaiodobenzylguanidine (MIBG) scintigraphy. The
      desensitization level of beta-adrenoceptors was assessed as the net increase in
      peak positive left ventricular (LV) dP/dt during intracoronary dobutamine
      infusion. Arterial NE concentrations were determined at baseline. To obtain
      control values, we performed MIBG scintigraphy and determined baseline NE
      concentration in 12 normal subjects. Cardiac MIBG uptake was significantly
      decreased in patients as compared with controls. This decrease was related to the
      severity of the disease based on hemodynamic indexes. The inotropic response to
      intracoronary dobutamine infusion of heart failure patients correlated with both
      increased baseline NE concentration and diminished cardiac MIBG uptake (r = 
      0.63, p less than 0.01 and r = 0.73, p less than 0.001, respectively). These
      findings indicate that the desensitization process is related both to impaired
      neuronal NE uptake function and increased circulating NE concentrations.
      Moreover, a subset of 11 patients with moderate heart failure was identified who
      had diminished cardiac MIBG uptake but normal circulating NE concentrations. This
      suggests that impairment of the NE uptake function is an early mechanism of
      desensitization in idiopathic cardiomyopathy. Cardiac MIBG imaging may be a
      noninvasive means to assess severity of heart failure patients and may also be
      used to evaluate therapy effects on myocardial alterations of the adrenergic
      pathway.

PMID- 1375675
TI  - Prolonged inhibition of local angiotensin-converting enzyme after single or
      repeated treatment with quinapril in spontaneously hypertensive rats.
AB  - Plasma and tissue angiotensin-converting enzyme (ACE) activities were measured in
      spontaneously hypertensive rats (SHR) after single or repeated oral (p.o.)
      treatment with a hypotensive dose (1 mg/kg) of quinapril and compared with those
      after administration of enalapril (1 mg/kg). The degree of ACE inhibition in
      response to quinapril varied in tissues; marked inhibition was observed in aorta,
      lung, and plasma by single treatment with quinapril, and inhibition in plasma and
      aorta caused by quinapril was more potent than that caused by enalapril. The
      prolonged ACE inhibition was observed in the aorta, a target organ, by repeated
      treatment with quinapril for 2 weeks. These results indicate that quinapril has a
      good pharmacokinetic profile, namely rapid absorption and easy penetration to the
      target organ. In addition, quinapril produced greater inhibition of cardiac ACE
      than did enalapril after either p.o. or intravenous (i.v.) administration,
      suggesting the beneficial effects of quinapril in treatment of congestive heart
      failure (CHF).

PMID- 1375676
TI  - Spasmolytic action of nicorandil in canine conductive coronary arteries in vivo
      is not modified by glibenclamide.
AB  - The spasmolytic effects of nicorandil, cromakalim, and nitroglycerin on coronary
      arteries were investigated by angiographic technique in anesthetized dogs. With
      intracoronary arterial (i.a.) U 46619, a thromboxane A2 mimetic, the diameter of
      coronary arteries decreased in a sustained manner by 36.1 +/- 1.6% from control
      levels (coronary spasm). With a successive i.a. injection of nicorandil (300
      micrograms), cromakalim (30 micrograms), or nitroglycerin (3 micrograms), the
      diameter recovered control levels (102.9 +/- 3.9, 96.8 +/- 5.6, and 100.1 +/-
      4.3%, respectively). In dogs treated intravenously (i.v.) with glibenclamide, a
      pharmacologic antagonist of K-channel openers, the spasmolytic effect of
      cromakalim was significantly reduced, whereas the activity of nicorandil or
      nitroglycerin remained unaffected. We also investigated a possible modification
      by glibenclamide of the increase in coronary blood flow (CBF) induced by i.a.
      nicorandil and cromakalim in anesthetized dogs. The dose-dependent blood flow
      responses to cromakalim and nicorandil were significantly attenuated by
      glibenclamide, whereas the response to nitroglycerin remained unaffected. These
      results suggest that the spasmolytic effect of nicorandil on canine conductive
      coronary vessels is not mediated by K-channel opening but by a nitroglycerin-like
      action and that the dilatation of resistive coronary vessels induced by
      nicorandil may be largely due to its action as a K-channel opener.

PMID- 1375677
TI  - Protective effects of G 619, a dual thromboxane synthase inhibitor and
      thromboxane A2 receptor antagonist, in splanchnic artery occlusion shock.
AB  - Splanchnic artery occlusion (SAO) shock was induced in anesthetized rats by
      clamping the celiac trunk and the superior mesenteric artery for 45 min. The
      arteries were then released and survival rate, mean survival time, mean arterial
      blood pressure (MAP), plasma levels of thromboxane B2 (TxB2) and 6-keto-PGF1
      alpha, and the phagocytotic activity of peritoneal macrophages were evaluated.
      Shocked animals died within 89 +/- 10 min, while all sham-shocked rats survived
      greater than 3 h. SAO shock produced relevant changes in MAP, significantly
      increased plasma levels of TxB2 and 6-keto-PFG1 alpha, and decreased peritoneal
      macrophage phagocytotic activity. The administration of G 619, a dual thromboxane
      synthase inhibitor/thromboxane A2 receptor antagonist (50 mg/kg, 15 min before
      SAO shock) significantly increased survival time (190 +/- 13 min) and survival
      rate, reduced plasma levels of TxB2, and partially restored the impairment in
      peritoneal macrophage phagocytosis. Finally, the administration of G 619 had
      beneficial effects on changes in MAP-induced bay SAO shock. These data further
      confirm the involvement of TxA2 in SAO shock and suggest that G 619 may have
      positive effects in low-flow states.

PMID- 1375678
TI  - Syst-Eur--a multicenter trial on the treatment of isolated systolic hypertension
      in the elderly: first interim report.
AB  - Syst-Eur is a multicenter placebo-controlled outcome trial designed by the
      European Working Party on High Blood Pressure in the Elderly to investigate the
      effect of antihypertensive treatment on the incidence of stroke in elderly
      patients with isolated systolic hypertension (ISH). Eligible patients must be at
      least 60 years old and have a systolic blood pressure averaging 160-219 mm Hg
      with a diastolic blood pressure less than 95 mm Hg. The present paper is an
      interim report on the first 316 patients randomized into this trial. The placebo
      (n = 170) and active treatment (n = 146) groups were similar at randomization
      with respect to age (73 +/- 8 years; mean +/- SD), sitting blood pressure (178 +/
      12 mm Hg systolic; 85 +/- 7 mm Hg diastolic), percentage of men (34%), and
      percentage of patients with cardiovascular complications (29%). After
      randomization blood pressure fell more (p less than 0.001) in patients on active
      treatment than in those in the placebo group (19 +/- 20 mm Hg systolic; 6 +/- 10
      mm Hg diastolic vs. 7 +/- 19 and 1 +/- 10 mm Hg for sitting blood pressure). This
      first interim report on the Syst-Eur trial demonstrates that a multinational
      trial in elderly patients with ISH is feasible and that a significant blood
      pressure difference between the two treatment groups can be achieved and
      maintained. New centers are being recruited in order to randomize a total of
      3,000 patients.

PMID- 1375680
TI  - Electrophysiologic effects of sotalol on the immature mammalian heart.
AB  - Sotalol is a beta-blocker with class III antiarrhythmic properties that has
      recently been used in children for the treatment of supraventricular and
      ventricular arrhythmias. However, little is known about its electrophysiologic
      effects on the immature heart. Using intracardiac electrocardiographic recordings
      and stimulation techniques, 15 canine neonates (8-15 days) and 15 adult mongrel
      dogs were studied with cumulative doses of sotalol (0.5, 1, 2, and 4 mg/kg plus
      an additional dose of 8 mg/kg for neonates). Heart rate decreased significantly
      in the two groups, but more in adult dogs (-43% in adult dogs versus -25% in
      neonates, p less than 0.05). There was no significant change for QRS duration and
      His-Purkinje system conduction time interval. QT and atrioventricular nodal
      conduction time intervals increased in adult dogs and neonates. Sinus node
      recovery time increased significantly in the two groups, but more in adult dogs.
      Refractory periods of the atrioventricular (AV) node increased significantly in
      neonates. Atrial flutter was no longer inducible in 12 of 15 neonates after the 2
      mg/kg dose. Atrial effective refractory period increased significantly more in
      neonates (96%, p less than 0.001) than in adult dogs (58%, p less than 0.001).
      Ventricular effective refractory periods increased significantly both in neonates
      (46%) and adult dogs (50%), in a similar way. In conclusion, sotalol has greater
      electrophysiologic effects on the immature heart at the atrial level when
      compared to the adult, and similar effects on the refractory period of AV node
      and ventricle.

PMID- 1375679
TI  - Effects of oral isradipine on left ventricular function at rest and during
      exercise in patients with stable chronic angina: a double-blind, placebo
      controlled crossover study.
AB  - We evaluated the effects of a single oral dose of 5 mg of isradipine compared to
      placebo in a randomized, double-blind, crossover study using gated radionuclide
      angiography at rest and during exercise in 20 patients with stable chronic
      angina. Isradipine improved both anginal symptomatology and ST-segment depression
      during exercise, with a concomitant favorable effect on the isotopic parameters
      exploring systolic and diastolic left ventricular function. There was a marked
      increase of the ejection fraction during exercise with isradipine compared to
      placebo (61 +/- 14% vs. 55 +/- 15%, respectively, p less than 0.001) as well as a
      significant improvement in the peak ejection rate and the peak filling rate at
      rest [2.56 +/- 0.62 vs. 2.16 +/- 0.54 end diastolic volume (EDV) per second and
      2.14 +/- 0.59 vs. 1.87 +/- 0.37 EDV/s, respectively] and during exercise (3.49 +/
      0.97 vs. 3.10 +/- 1.07 EDV/s and 4.05 +/- 1.34 vs. 3.65 +/- 1.25 EDV/s,
      respectively). We conclude that isradipine has a beneficial effect on the
      clinical and electrocardiographic signs of exercise-induced ischemia, leading to
      a significant improvement of the systolic and diastolic parameters of left
      ventricular function. Therefore, isradipine is potentially a useful treatment for
      patients with exertional angina and hypertension, alone or associated with beta
      blocker medication.

PMID- 1375681
TI  - Voltage-dependent modification of Vmax recovery from use-dependent block by
      pirmenol in guinea pig papillary muscles: comparison with other class I drugs.
AB  - Voltage-dependent modification of Vmax (the maximum upstroke velocity of the
      action potential) recovery from use-dependent block (UDB) by pirmenol was
      examined and compared with those observed with other Class I drugs using standard
      microelectrode techniques. A partial depolarization of the resting membrane by
      increasing extracellular potassium concentration ([K+]o) from 4 to 8 mM
      potentiated UDB at 2 Hz stimulation by any of the following drugs: pirmenol (10
      microM), disopyramide (20 microM), pentisomide (50 microM), quinidine (20
      microM), mexiletine (30 microM), and flecainide (5 microM). The recovery time
      constants from UDB of quinidine and mexiletine were prolonged and that of
      flecainide was unchanged in 8 mM [K+]o. However, the recovery time constant from
      UDB of pirmenol was shortened in high K+ solution, as observed with disopyramide
      and pentisomide. Thus, disopyramide and its analogues, including pirmenol, show a
      voltage dependency of recovery process, which is different from those of other
      class Ia, Ib, and Ic drugs. The main unblocking pathway of disopyramide and its
      analogues from sodium channels during diastolic interval may be different from
      that of other Class I drugs.

PMID- 1375682
TI  - Effect of antihypertensive treatment with nitrendipine on left ventricular mass
      and diastolic filling in patients with mild to moderate hypertension.
AB  - Nitrendipine is a dihydropyridine calcium antagonist that may be active when
      administered once daily. The aim of the study was to assess the effect of
      antihypertensive treatment with nitrendipine (20-40 mg) on left ventricular mass
      and diastolic function. Forty patients with mild to moderate hypertension
      (diastolic pressure greater than or equal to 90 and less than or equal to 114 mm
      Hg) were enrolled; a complete echo Doppler examination was performed at baseline,
      and 8 and 12 months after treatment in order to measure left ventricular mass and
      diastolic and systolic function. Only 28 patients completed the study follow-up.
      At month 8 nitrendipine had already successfully reduced blood pressure (mean 122
      +/- 9  to 92 +/- 10 mm Hg) without modifying heart rate, and left ventricular
      mass index (150 +/- 48 to 123 +/- 34 g/m2), with a further reduction at month 12.
      Isovolumic relaxation time was reduced at month 8 from 138 +/- 28 to 111 +/- 17
      ms, but the diastolic pattern was completely modified only after 1 year, with a
      normalization of deceleration time (from 220 +/- 35 to 188 +/- 12). Systolic
      function did not change. Our results indicate that nitrendipine is a powerful
      antihypertensive agent that reduces left ventricular mass, but requires a longer
      period of time to improve diastolic filling pattern.

PMID- 1375683
TI  - Effects of the ACE inhibitor, perindoprilat, and of angiotensin II on the
      transient inward current of guinea pig ventricular myocytes.
AB  - Hypothetically, certain ischemic and reperfusion arrhythmias may result from the
      activity of the calcium-dependent transient inward current. The effects of the
      angiotensin converting enzyme inhibitor, perindoprilat, on the transient inward
      current of guinea pig ventricular myocytes were studied. The transient inward
      current was evoked by superfusing the cell with a modified Tyrode's solution (5.4
      mM CaCl2 and 0.54 mM KCl). Repetitive voltage clamp steps from a holding
      potential of -55 to +20 mV (1,000 ms, 0.1 Hz) were applied while dialyzing the
      cell internally. When administered simultaneously with the change over to the low
      K+ high Ca2+ solution, perindoprilat (1 microM) decreased the transient inward
      current from -9.55 +/- 0.31 to -3.24 +/- 0.24 microA/cm2 (p less than 0.05). A
      similar decrease was observed when perindoprilat was administered after first
      inducing the transient inward current. Perindoprilat also protected from the
      effects of norepinephrine (0.01 and 0.1 microM), which increased the amplitude of
      the transient inward current from -9.76 +/- 0.17 and -9.99 +/- 0.32 microA/cm2 at
      the end of the 15-min control period to -11.13 +/- 0.67 and -12.67 +/- 0.49
      microA/cm2, respectively (p less than 0.05). The effects of perindoprilat were
      independent of angiotensin II, which in this preparation decreased the transient
      inward current. Based on our results, we conclude that perindoprilat decreases
      the transient inward current and prevents the action of norepinephrine on the
      transient inward current. The direct effect of the angiotensin converting enzyme
      inhibitor observed on the transient inward current might explain why angiotensin
      converting enzyme inhibitors reduce calcium-dependent ouabain-induced or
      reperfusion arrhythmias.

PMID- 1375684
TI  - Modulation of inotropic therapy by venodilation in acute heart failure: a
      randomised comparison of four inotropic agents, alone and combined with
      isosorbide dinitrate.
AB  - The effects of four inotropic agents with differing ancillary properties [a
      cardiac glycoside (digoxin), a combined alpha- and beta-adrenergic agonist
      (dobutamine), a beta-adrenergic agonist (prenalterol), and a phosphodiesterase
      inhibitor (amrinone)] alone and with subsequent addition of isosorbide dinitrate
      were compared in 48 consecutive acute myocardial infarction patients with
      radiographic and haemodynamic (pulmonary artery occluded pressure greater than 18
      mm Hg) left ventricular failure. All agents with the exception of dobutamine
      reduced the elevated left heart filling pressure; only digoxin and dobutamine
      augmented the cardiac stroke volume index. All drugs except digoxin reduced the
      SVRI; an arteriolar constrictor response was evident 60 min after digoxin and a
      tachycardia resulted after combined alpha- and beta- and beta-adrenergic
      stimulations (dobutamine and prenalterol, respectively). The addition of
      isosorbide dinitrate reversed the inotrope-induced elevations of systemic
      arterial pressure and resulted in additional reductions in left heart filling
      pressure. These data suggest that, in the absence of substantial venodilator
      properties in an inotropic compound, reduction in elevated left heart filling
      pressure is not achieved with inotropic therapy alone in acute left ventricular
      failure and combining a venodilator may be haemodynamically advantageous.

PMID- 1375686
TI  - Effect of dietary sunflower seed oil on the severity of reperfusion-induced
      arrhythmias in anesthetized rats.
AB  - Myocardial ischemia followed by reperfusion was produced in artificially
      respirated, open-chest rats. Coronary artery ligation for 6 min rarely evoked
      arrhythmias; however, reperfusion after this period rapidly produced severe
      dysrhythmias in all control animals. Reperfusion after 12 min of ischemia
      produced less frequent dysrhythmias than after coronary occlusion for 6 min.
      Feeding of a linoleic acid-rich diet, applying 12% sunflower seed oil in rat food
      pellet for 4 weeks, decreased the incidence of reperfusion-induced ventricular
      fibrillation both after 6 min (2/15 vs. 7/11) and 12 min (0/11 vs. 2/8) of
      myocardial ischemia and the incidence of other arrhythmias was also decreased.
      The number of animals developing no arrhythmias during reperfusion was increased
      (8/15 after 6 min of ischemia, 4/11 after 12 min of ischemia vs. 0/11 and 0/8 in
      controls, respectively). Our results indicate that increased dietary consumption
      of linoleic acid decreased the occurrence of life-threatening arrhythmias both
      during the acute phase of myocardial ischemia and during reperfusion in
      anesthetized rats.

PMID- 1375685
TI  - Coronary reperfusion rates in acute myocardial infarction patients after
      thrombolytic treatment with anistreplase: correlation with the delay from onset
      of symptoms to treatment: a review of 424 case records of patients admitted to
      coronary reperfusion studies with anistreplase.
AB  - The individual data for 424 acute myocardial infarction patients from 15
      reperfusion studies conducted with anistreplase were reviewed to assess the
      correlation between the delay onset of symptoms to treatment and reperfusion of
      the coronary artery. The patients had a mean age of 56 years and 85.4% were male.
      All patients had a baseline angiogram showing an occluded coronary artery.
      Anistreplase was given in doses ranging from 3.75 to 35 IU (60% of patients
      received 30 IU). The mean delay between onset of symptoms to treatment was 3 h 29
      min and reperfusion was observed in a total of 61.1% of patients. There was a
      highly significant correlation between reperfusion and the delay from onset of
      symptoms to treatment (p less than 0.001). A multivariate logistic regression was
      performed adjusting for age, sex, location of infarct, dose, and concomitant
      treatment. The only remaining statistically significant prediction factor for
      reperfusion was the delay between onset of symptoms to treatment (p less than
      0.001). In conclusion, the ability of anistreplase to cause the lysis of coronary
      thrombi appears to be increasingly important as the delay from onset of symptoms
      to treatment is decreased. This may contribute to the lower mortality rate
      observed with early fibrinolytic treatment.

PMID- 1375687
TI  - Effects of sinoaortic denervation on the reflex actions of digoxin and a polar
      aminocardenolide.
AB  - To determine the role of carotid sinus and aortic arch baroreceptors in the
      reflex cardiac sympathetic nerve activity (SNA) responses to administration of
      ASI-222, a polar aminocardenolide, and to digoxin, a neutral cardenolide, we used
      anesthetized dogs from which these reflex receptor areas had been removed. The
      SNA was measured in postganglionic fibers from the stellate ganglion. After we
      made baseline measurements, we infused either ASI-222 or digoxin intravenously
      (i.v.) at dose rates that produce cardiac arrhythmias in approximately 100 min
      (0.7 and 1.2 micrograms/kg/min), respectively. Our data indicate that with
      sinoaortic baroreceptors removed, progressive infusion of digoxin increases
      cardiac SNA. In contrast, cardiac SNA decreases progressively during continuous
      infusion of ASI-222. In saline-treated dogs, SNA was not significantly altered.
      In another series of experiments, we examined the effects of these drugs and
      saline on cardiac vagal afferent nerve activity (VANA). ASI-222 (50 micrograms/kg
      i.v. in 10 min) caused a progressive increase in cardiac VANA in a 60-min
      observation period. Neither digoxin, at less than or equal to 120 micrograms/kg
      i.v. in 100 min, nor saline altered VANA. Digoxin appears to reduce SNA by
      interacting with the carotid sinus and aortic arch baroreceptors, which are
      myelinated. It does not affect VANA acutely. In contrast, ASI-222 appears to
      decrease cardiac SNA by interacting with other reflex receptor areas--the
      unmyelinated cardiopulmonary afferent nerve endings, particularly cardiac
      mechanoreceptors.

PMID- 1375688
TI  - Proarrhythmic effects of procainamide and tocainide in a canine infarction model.
AB  - A canine model of myocardial infarction (MI) was used to study the type and
      frequency of ventricular antiarrhythmic and proarrhythmic effects due to
      procainamide and tocainide and the risk factors associated with development of
      proarrhythmia. An anterior MI was created by a 2-h occlusion of the left anterior
      descending artery (LAD) with complete reperfusion. Programmed ventricular
      stimulation was performed on two occasions after MI, on days 4-6 and on days 8
      10, before drug and during antiarrhythmic drug infusion at three dose levels. The
      antiarrhythmic drugs were given in a randomized cross-over design. Only
      procainamide caused a dose-dependent increase in QRS, JTc, and right ventricular
      effective refractory period (ERP). Neither procainamide nor tocainide made
      sustained ventricular tachycardia (VT) noninducible, but procainamide slowed the
      tachycardia rate. Both drugs successfully made ventricular fibrillation (VF)
      noninducible: procainamide in 78% of trials and tocainide in 50% of trials.
      Proarrhythmia (development of inducible VT during drug when not present before
      drug or inability to terminate VT during drug administration) developed in 29% of
      dogs that received procainamide and 25% of dogs that received tocainide. There
      was no apparent correlation of QRS, JTc, and right ventricular ERP after drugs
      and proarrhythmia due to procainamide or tocainide. There was no significant
      difference in the size of MI between dogs with one or more proarrhythmic response
      to either drug and dogs that had no proarrhythmia. In this model, procainamide
      and tocainide had no antiarrhythmic efficacy for VT, but had moderate
      proarrhythmia potential that was unpredictable.

PMID- 1375689
TI  - Cardiovascular effects of a novel calcium entry blocking and selective beta 1
      adrenoceptor blocking agent, YM-16151-4, in anesthetized and conscious dogs.
AB  - Cardiovascular effects of YM-16151-4, a combined calcium entry blocking and beta
      1-adrenoceptor blocking agent, were evaluated in dogs. In anesthetized dogs, YM
      16151-4 (0.01-1 mg/kg intravenously, i.v.) dose-dependently increased coronary
      blood flow (CBF) and decreased mean blood pressure (MBP), total peripheral
      resistance (TPR), dP/dtmax, double product, and left ventricular (LV) work
      without increasing heart rate (HR) and cardiac output (CO). YM-16151-4 increased
      vertebral blood flow as well as CBF, but had no effect on carotid, mesenteric,
      renal, and femoral blood flow. Coronary vasodilating activity of YM-16151-4 was
      also observed after intracoronary artery injection (i.a.). In anesthetized and
      vagotomized dogs, YM-16151-4 dose-dependently inhibited isoproterenol (0.2
      micrograms/kg i.v.)-induced tachycardia and decrease in diastolic BP (DBP), with
      ED50 values of 0.039 and 0.52 mg/kg i.v., respectively. In conscious dogs, YM
      16151-4 (0.1-1 mg/kg i.v.) produced a dose-dependent hypotensive effect with no
      effect on HR or PQ-interval. The hypotensive effect of YM-16151-4 (0.3 and 1
      mg/kg i.v.) reached its maximum approximately 1-2 h after each dosing and lasted
      6-8 h. These results suggest that YM-16151-4 actually behaves as a hybrid
      compound, combining calcium entry blocking and beta 1-adrenoceptor blocking
      activities, and that this compound could be a novel long-acting antianginal and
      antihypertensive agent.

PMID- 1375690
TI  - Failure of AICA riboside to limit infarct size during acute myocardial infarction
      in rabbits.
AB  - This study examined whether the adenosine potentiator, 5-aminoimidazole-4
      carboxamide riboside (AICAr), could limit tissue necrosis during acute myocardial
      infarction in rabbit hearts with minimal coronary collateral flow. Forty-four
      rabbits underwent 45 min of ischemia with or without coronary reperfusion for 180
      min. Five groups were studied. Saline or AICAr (20 mg/kg, i.v.) was administered
      as a bolus either 10 min before coronary occlusion or 10 min before the onset of
      coronary reperfusion. The anatomic risk zone size was assessed by radiolabeled
      microsphere autoradiography and the area of tissue necrosis was defined using the
      tetrazolium staining method. Coronary collateral flow in the central ischemic
      zone was assessed using the radiolabeled microsphere technique. No differences
      were observed for tissue necrosis (normalized to risk zone size) for saline- and
      AICAr-treated rabbits (66.2 +/- 10.9% vs. 70.8 +/- 19.9%, p = NS) subjected to 45
      min of coronary occlusion without reperfusion. Similarly, tissue necrosis in
      rabbit hearts with 45 min of coronary occlusion followed by 180 min of
      reperfusion was not significantly reduced when AICAr was administered either 10
      min before ischemia or 10 min before reperfusion (79.8 +/- 17.5 and 76.4 +/-
      8.1%, respectively) compared to saline-treated controls (68.1 +/- 22.7%).
      Coronary collateral flow in these hearts was almost nonexistent. The risk zone
      size and cardiac hemodynamics were similar between the treatment groups. These
      results demonstrate that AICAr was unable to limit myocyte necrosis when
      administered either before ischemia or before coronary reperfusion in this
      experimental preparation of acute myocardial infarction.

PMID- 1375691
TI  - Active and passive effects of antihypertensive drugs on large artery diameter and
      elasticity in human essential hypertension.
AB  - The effects of antihypertensive drugs on the large arteries consist of two parts:
      the passive effect due to the change in pressure and the active effect, the drug
      action per se. This study proposes a method of dissociating the passive effect
      from the active effect. The diameter of the arterial artery was determined by the
      pulsed Doppler method and the pulse wave velocity of the brachioradial artery by
      mecanography. Arterial compliance was calculated by the Bramwell-Hill formula.
      Active and passive effects were determined by a logarithmic pressure-diameter
      model. This model was supported by in situ direct measurements of blood pressure
      and diameter in a segment of the femoral artery in dogs. Six drugs, cadralazine,
      ketanserin, medroxalol, nitrendipine, captopril, and isosorbide dinitrate,
      administered orally, were tested in 70 essential hypertensive patients. For all
      drugs, the pressure reduction induced a passive decrease in arterial diameter (p
      less than 0.02 to p less than 0.01). Cadralazine actively decreased arterial
      diameter (p less than 0.01), ketanserin had no active effect on diameter, and
      medroxalol, nitrendipine, captopril, and isosorbide dinitrate actively increased
      arterial diameter (p less than 0.05, p less than 0.01, p less than 0.01, and p
      less than 0.01, respectively). For all drugs, the pressure reduction also induced
      a passive increase in arterial compliance (p less than 0.05 to p less than 0.01).
      However, only nitrendipine, captopril, and isosorbide dinitrate actively
      increased arterial compliance (p less than 0.01, p less than 0.05, and p less
      than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375692
TI  - Sex and age as factors influencing the vascular reactivity in Watanabe heritable
      hyperlipidaemic (WHHL) rabbits: a pharmacological and morphological study of the
      hepatic artery.
AB  - The responses to vasoactive agents and the fine structure of hepatic arterial
      ring segments from male and female Watanabe heritable hyperlipidaemic (WHHL)
      rabbits (4, 6, and 12 months) were compared with those of age- and sex-matched
      New Zealand White (NZW) rabbits. In males only, KCl-induced contractions were
      reduced in WHHL rabbits compared with NZW rabbits. In male and female WHHL
      rabbits, maximum noradrenaline-induced contractions and sensitivity to
      noradrenaline were greater than those of male and female NZW rabbits. In female
      WHHL and NZW rabbits only, maximum noradrenaline-induced contractions and the
      EC50 values were reduced at 6 months. Endothelium-dependent relaxation: In
      females only, maximum relaxant responses and the sensitivity of WHHL rabbits to
      acetylcholine increased with age, while there was a decrease in NZW rabbits.
      Similarly, relaxation to substance P increased with age in WHHL rabbits and
      decreased in NZW rabbits, but this occurred in both male and female animals. In
      addition, substance P-induced relaxation in female WHHL rabbits was greater than
      in male WHHL rabbits. Endothelium-independent relaxation: In both male and female
      WHHL rabbits, calcitonin gene-related peptide-induced and vasoactive intestinal
      polypeptide-induced relaxation did not change with age. However, there was an age
      related decrease in the response of NZW rabbits to these peptides. Electron
      microscopic evaluation of hepatic arteries from WHHL rabbits showed occasional
      ruptures in the internal elastic lamina at 4 months. At 6 months, widespread
      intimal thickening associated with smooth muscle cell migration was apparent, but
      this became less obvious at 12 months. No obvious differences in structure
      between male and female hepatic arteries were observed. It is suggested that a
      "compensatory vasodilatation" develops in atherosclerosis, initially at the level
      of the endothelium, and then with the progression of the disease extends to
      changes in the smooth muscle. This may occur in order to offset the thickening of
      the arterial wall. Sexual dimorphism in vascular reactivity has been
      demonstrated.

PMID- 1375693
TI  - Effects of milrinone on systemic capacitance vessels in relation to venous return
      and right ventricular pump function.
AB  - To investigate the effect of milrinone (MIL) on systemic capacitance vessels, we
      measured the mean circulatory filling pressure (MCP) in anesthetized open chest
      dogs. We measured hemodynamic parameters (a) at baseline blood volume (BV), (b)
      immediately after bloodletting (5 ml/kg), and (c) immediately after dextran
      injection (5 ml/kg). These measurements were taken in a control group (n = 8) and
      in a MIL group (n = 8), where MIL (100 + 2.5 micrograms/kg/min) was administered
      i.v. The extra volume (EV) was obtained by extrapolating the straight line that
      was fit to the MCP-BV plot. MIL significantly decreased the EV, from 22.8 +/- 1.0
      to 19.1 +/- 0.4 ml/kg, indicating that MIL dilates the systemic capacitance
      vessels. MIL shifted the right ventricular output curve to the left and upward
      and shifted the venous return curve to the left and rotated it clockwise. Thus,
      venous return was increased by decreasing the resistance to venous return and by
      improving right ventricular pump function. Next we evaluated the effects of MIL
      (100 micrograms/kg) on systemic capacitance and resistance vessels from changes
      seen in the MCP and the total peripheral resistance (TPR), respectively. In the
      untreated dogs, MIL decreased TPR significantly without affecting MCP. In dogs
      pretreated with total spinal anesthesia or phenoxybenzamine, MIL significantly
      decreased both MCP and TPR. This suggests that the intrinsic venodilator action
      of MIL is modified by the baroreflex in untreated animals. MIL decreased the MCP
      and TPR elevated previously by norepinephrine. One would, therefore, predict that
      MIL would dilate the systemic capacitance vessels in patients with congestive
      heart failure.

PMID- 1375694
TI  - CD5+ B lymphocytes correspond to generalist lymphocytes predicted by a
      computational model of affinity maturation.

PMID- 1375695
TI  - Acute lymphoblastic leukemia with the (4;11) translocation: combined cytogenetic,
      immunological and molecular genetic analyses.
AB  - Five cases of acute leukemia (AL) with the t(4;11) translocation were
      investigated for the immunoglobulin heavy chain, kappa, lambda, TCR beta and TCR
      gamma gene rearrangements. All patients presented with high-risk features and had
      survival times of less than two years. Two cases were classified by immunological
      phenotyping as acute null-AL(L), one case as pre B-cell ALL (CD10+) and two cases
      expressed both immature B-cell markers CD19 and CD24 and myelomonocytic markers
      CD15 and CD14, suggesting mixed lineage leukemia. In two cases more than two
      rearranged fragments for the immunoglobulin heavy chain gene could be detected by
      Southern blot analysis. In the other cases at least one allele of the
      immunoglobulin heavy chain gene was rearranged. Germline configuration of the T
      cell receptor genes and lack of light chain gene rearrangement suggest that an
      early B-precursor cell is involved in the transformational events in these cases
      of ALL. Our own and published data indicate that acute leukemia with t(4;11)
      translocation might be more frequently associated with more than two rearranged
      fragments for the immunoglobulin heavy chain genes and run a very aggressive
      course.

PMID- 1375697
TI  - Cytokine induction of leucocyte adhesion molecule-1 (LAM- 1) expression on
      chronic lymphocytic leukaemia cells.
AB  - Leucocyte adhesion molecule 1 (LAM-1) participates in the binding of human
      leucocytes to high endothelial venules in peripheral lymph nodes. Other adhesion
      receptors which are involved include CD44 and the integrin family, CD11/CD18. In
      this study, B-cell chronic lymphocytic leukemia (B-CLL) cells were examined for
      the expression of these adhesion molecules, and for the way in which cytokines
      are able to modulate the levels of these receptors. B-CLL cells express
      significant but variable levels of LAM-1 and high levels of CD44. In contrast,
      these cells exhibit very low or absent amounts of surface CD11a, CD11b, or CD11c.
      Most CLL cells expressed no detectable levels of intercellular adhesion molecule
      1 but some cases show levels of up to 30%. Following 24 h incubation with
      interferon alpha (500 U/ml), surface LAM-1 expression on peripheral blood E
      negative cells from CLL patients rose to 330 +/- 127% of levels on control cells
      incubated with medium alone (n = 13, p less than 0.0005). Interleukin 4 (1 ng/ml)
      and interferon gamma (100 U/ml) also increased surface LAM-1 levels on these
      cells to 218 +/- 119% (n = 8, p less than 0.001) and 245 +/- 116% (n = 5, p less
      than 0.001) of control levels respectively. Induction of LAM-1 expression
      occurred over 48 h (greater than 50% of the increase was seen in the first 24 h)
      in a dose-dependent manner and required protein synthesis. The induction of LAM-1
      expression on the malignant cells may, by altering the homing behaviour of these
      cells, relate to the reduction in peripheral leukaemic cells seen following
      treatment with interferon alpha in CLL.

PMID- 1375696
TI  - Surface markers in adult acute myeloblastic leukemia: correlation of CD19+, CD34+
      and CD14+/DR--phenotypes with shorter survival. Groupe d'Etude Immunologique des
      Leucemies (GEIL).
AB  - The immunophenotype of blast cells was investigated in a multicentric study of
      154 adult acute myeloblastic leukemias (AMLs). A panel of 27 monoclonal
      antibodies (MoAbs) was tested in indirect immunofluorescence. Expression of CD14
      (UCHM1), CD19 (SB4), CD36 (OKM5), and HLA-DR were associated with higher mean
      leucocyte counts. CD14 expression correlated with low hemoglobin level and the
      absence of CD33 (MY9) with low platelet counts. Extramedullary disease was
      associated with CD16 (Leu11b) and HLA-DR antigen positivity. The study of
      relationships between surface markers and FAB criteria confirmed the predominant
      expression of CD14 in the M5 sub-group (p less than 0.000001) and the association
      of CD19 and CD36 with monocytic M4/M5 subgroups (respectively p less than 0.00002
      and p less than 0.000001). All patients received an induction therapy including
      an anthracycline and cytarabine. The median follow-up was 13 months. The
      achievement of complete remission (CR) was inversely correlated with CD34 (B13C5)
      and CD19 expression: CR was obtained in 31 of 59 (53%) CD34-positive AML versus
      64 of 75 (85%) CD34-negative cases (p less than 0.0001) and 11 of 24 (46%) CD19
      positive versus 95 of 122 (78%) CD19-negative cases (p less than 0.01). In
      univariate analysis, a longer survival was associated with CD33 expression and
      the combined phenotypes CD36+/CD19- and CD16+/CD14-. Conversely, the
      CD18(IOT18)+/CDw65(VIM2)- phenotype was related to shorter survival. The
      expression of CD19, of CD34, and of the combined phenotype CD14+/DR--correlated
      with shorter survival as demonstrated both in univariate and multivariate
      analysis (p less than 0.03 in each case in multivariate analysis).

PMID- 1375698
TI  - Characterization of murine hemopoietic-supportive (MS-1 and MS-5) and non
      supportive (MS-K) cell lines.
AB  - Characteristics of hemopoietic-supportive (MS-1 and MS-5) and non-supportive (MS
      K) cell lines were compared. Supportive cells adhered to hemopoietic stem cells
      and produced granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas
      non-supportive cells did not adhere to hemopoietic cells and only produced
      macrophage colony-stimulating factor. Both cell lines produced substantial levels
      of IL-6 and steel factor (SLF) which is reportedly a stem-cell factor. Northern
      blot analysis revealed that SLF but neither c-kit nor interleukin 3 (IL-3) mRNA
      was detectable in these cell lines, although IL-3-like activity was found in the
      supernatant of MS-5 cell culture. These observations suggest that the hemopoietic
      supportive function of stromal cells may reside in adherence of stem cells, and
      production of GM-CSF probably in combination with SLF. SLF may be transferred
      from stromal cells directly to stem cells through adhesion of stem cells to
      supportive stromal cells.

PMID- 1375699
TI  - Effects of cryopreservation on the adherent layer of human long-term bone marrow
      cultures: study of cell phenotypes.
AB  - This report describes the effects of cryopreservation on the adherent layer of
      human long-term bone marrow cultures (HLTBMC). Stromal cells are believed to be
      the most important cells of medullar microenvironment to regulate hematopoiesis.
      To study effects of cryopreservation, we compared the cell phenotypes of adherent
      layers of fresh and frozen-thawed bone marrows. To characterize stromal cells we
      used monoclonal antibodies reacting with components of these cells (CGA-7 alpha
      SM and gamma SM actin isoforms; HHF-35, all muscle actin isoforms; BMS-1, stromal
      cell lysosomes). The other components studied were: fibronectin (BMS-2 monoclonal
      antibody) and hematopoietic cells (monoclonal antibodies against CD45, CD33, and
      CD14). Results show a decrease of cells positive for CGA-7, HHF-35, and BMS-1, in
      adherent layer of HLTBMC of frozen-thawed bone marrows. Expression of BMS-2 is
      unchanged, and CD45 and CD14-positive cells proportionately increased. These
      results are consistent with an impairment of stromal cell proliferation in frozen
      thawed marrows, without impairment of most stromal cell functions. The difference
      between stromal cell and hematopoietic cell kinetics seems to be an additional
      fact suggesting a different origin for both cell populations.

PMID- 1375700
TI  - In vitro responsiveness to interleukins and theophylline of CD16+, CD56- natural
      killer cells in a patient with chronic granular lymphocyte disorder.
AB  - We report here the case of a 55-year-old patient with chronic granular lymphocyte
      disorder associated with moderate neutropenia. The majority of peripheral blood
      lymphocytes displayed a CD3-, CD8-, CD16+, CD56(NKH1)- phenotype. The patient's
      cells showed high spontaneous cytotoxic activity against K562 targets and
      developed the ability to kill the natural killer (NK)-resistant target Daudi
      following activation with interleukin 2 (IL-2). Simultaneously, IL-2 induced
      proliferation of these cells, albeit to a low level. The effects of IL-2 are
      likely to be mediated through the IL-2R beta chain (p70) which is expressed on
      these cells in the absence of the IL-2R alpha chain (p55, Tac). IL-4 was
      demonstrated to be inhibitory of both the cytotoxic and proliferative effects of
      IL-2. Thus, despite an unusual CD56- phenotype, the expanded lymphocyte
      population in this patient display functional and phenotypic properties of
      normal, non-activated NK cells. These cells probably represent the counterpart of
      a minor NK cell subpopulation, present in normal individuals at a low frequency,
      and which has never been fully characterized functionally. In addition, we show
      that the cytolytic activity of this NK cell population can be blocked in vitro in
      the presence of a cAMP analog or of theophylline, possibly providing new means of
      investigating the role of NK cell cytotoxicity on the pathogenesis of associated
      symptoms in such patients.

PMID- 1375701
TI  - PCR amplification of large genomic fragments from human and simian
      immunodeficiency virus infected cell lines.
AB  - Polymerase chain reaction (PCR) has been used to amplify the large fragments from
      viral genomic DNA of SIV from wild caught, asymptomatic Erythrocebus monkeys from
      Western Africa (Senegal) and also from HIV-2 infected cell lines. By using
      consensus primer sequences from highly conserved stretches of gag, pol and env
      genes, two halves of the viral genome of HIV-2 and SIV (isolated from west
      African Erythrocebus monkeys) have amplified by PCR. One half spans 5200 bp from
      within the U3 region of the 5' long terminal repeat (LTR) into pol gene and an
      overlapping fragment spans 3700 bp from the pol gene into U5 region of 3' LTR.
      Also fragments ranging from 1-2.3 kb from gag pol and env genes have been
      successfully amplified. Our data demonstrate that primers used to amplify large
      segments from viral DNA yield better results if they are derived from a consensus
      sequence of a highly conserved stretch of the viral genome.

PMID- 1375702
TI  - Differentiation of human prostate cancer from benign hypertrophy by in vitro 1H
      NMR.
AB  - In vitro 1H NMR spectra were acquired for perchloric acid extracts of tissue
      samples of human prostate. Seven patients were diagnosed with prostate cancer, 13
      with benign prostatic hypertrophy, and 3 with both conditions. Statistically
      significant differences between the cancer and benign groups were seen for the
      metabolite peak area ratios of citrate, creatine, and phosphorylcholine to
      alanine, and citrate to glutamate. There was no correlation of Gleason grade with
      any of the ratios measured for the cancer samples. Spectra from different
      sections of large tumors often yielded substantially different area ratios,
      confirming the heterogeneous nature of these prostate tumors.

PMID- 1375703
TI  - Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran
      magnetite particles.
AB  - Human lymphocytes were labeled with biotinylated anti-lymphocyte-directed
      monoclonal antibodies, to which streptavidin and subsequently biotinylated
      dextran-magnetite particles were coupled. This labeling resulted in a strong and
      selective negative contrast enhancement of lymphocyte suspensions at 2.0 T,
      caused predominantly by the specific increase of R2 with a small but significant
      specific increase of R1. The R1 was found to decrease with increasing field
      strength. The immunolabeling procedure described here may be used for the
      selective signal depletion of target cells in MR imaging.

PMID- 1375704
TI  - Analysis of tick-borne encephalitis virus antigens by monoclonal antibodies.
AB  - Monoclonal antibodies (MAbs) against Central European tick-borne encephalitic
      virus, strain Hypr, were used for determination and characterization of viral
      antigens of infected PS cells. The MAbs reacted in immunoblotting with flavivirus
      glycoprotein E (56 kD), and nonstructural protein NS3 (70 kD). According to
      enzyme immunoassay with infected cells, NS3 antigen is expressed in the
      plasmalemma.

PMID- 1375705
TI  - Pathogenesis of Graves' ophthalmopathy.

PMID- 1375706
TI  - Pancreatic carcinoma.

PMID- 1375707
TI  - Genetic screening for cystic fibrosis.
AB  - More than 98% of mutations causing cystic fibrosis can be detected in a Celtic
      population in Brittany, France. What, though, are the prospects for screening of
      entire populations for carriers?

PMID- 1375708
TI  - Function of maternal cytokeratin in Xenopus development.
AB  - Intermediate filaments are ubiquitous in eukaryotic cells, but their functions
      are poorly understood. The Xenopus oocyte contains both messenger RNA and protein
      products of cytokeratin and vimentin genes in non-overlapping arrays. The
      cytokeratin filaments contain dimers of the type I (acidic) subunit XLK3a(19),
      and the type II (basic) subunit XCK1(8), polymerized to form a cortical network.
      These are homologues of the human simple epithelial keratins 19 and 8,
      respectively. After the first few cell cycles following fertilization these
      filaments become restricted to the superficial cells of the blastula. We have
      depleted the oocyte's store of the type II cytokeratin mRNA by injecting
      antisense oligodeoxynucleotides (oligos) and studied the effect on embryonic
      development. As zygotic transcription does not commence until the late blastula
      stage, there are at least 9 hours in which to see the effect of loss of function
      of this mRNA. We report here that the cytokeratin filaments become depleted in
      the cortical cells of the embryo. As a result, there is a loss of the 'compacted'
      epithelial surface of the blastula, an inability to close a wounded surface and
      defective gastrulation.

PMID- 1375709
TI  - Characterization of tachykinin-induced ventral root depolarization in the
      neonatal rat isolated spinal cord.
AB  - Depolarization responses to tachykinin receptor agonists were recorded
      extracellularly from lumbar ventral roots of spinal cord isolated from neonatal
      rats (one to eight days post partum). All spinal cords were hemisected in the
      sagittal plane. In addition, in some hemisected cords, the dorsal horns were
      removed by means of a further cut, perpendicular to the first. In both hemisected
      and quadrisected spinal cords, reproducible depolarization responses were induced
      by low concentrations of the neurokinin-1-selective agonist substance P
      methylester (10 nM-1 microM) or of the neurokinin-3-selective agonist senktide (3
      300 nM). On both types of preparation, responses to substance P methylester (1
      microM) or senktide (300 nM) were of comparable size. The amplitude of the
      response to senktide (300 nM) was reduced by at least 88% in spinal cord
      preparations exposed to tetrodotoxin (0.5 microM) or to physiological medium
      containing magnesium chloride (20 mM). In contrast, under either of these
      conditions, concentration-response curves to substance P methylester were shifted
      rightward by 2.8-8.5-fold, with little effect on the maximum response. Responses
      to senktide were blocked selectively by the N-methyl-D-aspartate antagonist 3-[(+
      )-2-carboxypiperazine-4-yl]propyl-1-phosphonic acid (100 microM); the antagonist
      had little effect on substance P methylester-induced depolarization (mean
      concentration ratio 2.0). These results suggest that in the neonatal rat spinal
      cord, application of exogenous tachykinin agonists can induce ventral root
      depolarization by activation of neurokinin-1 and/or neurokinin-3 receptors. The
      response to stimulation of neurokinin-1 receptors has a major component likely to
      be due to a direct action at motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375710
TI  - Bilateral irradiation of head and neck induces an enhanced expression of
      substance P in the parasympathetic innervation of the submandibular gland.
AB  - Substance P and calcitonin gene-related peptide (CGRP) are present in nerve
      fibers innervating the submandibular gland. Radiotherapy of tumors in the head
      and neck region usually embraces the salivary glands in the irradiated field and
      consequently a dramatic decrease in salivary function is seen. In this study, the
      submandibular glands and ganglia of rats subjected to fractionated irradiation
      were examined by use of immunohistochemical techniques for demonstration of
      substance P and CGRP. Irradiation was given on five consecutive days (daily doses
      of 6-9 Gray) with unilateral or bilateral irradiation techniques. Specimens of
      control and experimental animals were processed in parallel. A marked increase in
      the expression of substance P in the ganglionic cells--presumably parasympathetic
      -and in the number of fibers showing substance P-like immunoreactivity in
      association with acini and small ducts was seen in response to bilateral
      irradiation. (Surprisingly, unilateral irradiation of the parotid area had no
      effect on peptide distribution in the irradiated gland and ganglion). No changes
      in the pattern of CGRP immunoreactivity occurred. In the trigeminal ganglion,
      which supplies the submandibular gland with the majority of the sensory substance
      P- and CGRP-containing nerve fibers, no changes in the expression of substance P
      or CGRP immunoreactivity were seen. The results suggest that bilateral
      irradiation leads to an increase in the synthesis of substance P-like substance
      in the parasympathetic ganglionic cells supplying the submandibular gland with
      secretory nerves, and can thus be an additional factor in explaining the altered
      secretory capacity of salivary glands.

PMID- 1375711
TI  - The OM series of terminal field-specific monoclonal antibodies demonstrate
      reinnervation of the adult rat dentate gyrus by embryonic entorhinal transplants.
AB  - Monoclonal antibodies OM-1 to OM-4 and IM-1 [Woodhams et al. (1991) Neuroscience
      46, 57-69] have complementary immunostaining patterns in the molecular
      (dendritic) layer of the adult rat dentate gyrus, with OM-1 to OM-4 selectively
      recognizing the outer (distal) two-thirds (i.e. the entorhinal afferent zone),
      and IM-1 the inner (proximal) one-third (i.e. the hippocampal
      commissural/associational zone). Immunoblotting suggests that OM-1 recognizes a
      single glycoprotein antigen of mol. wt around 93,000, and OM-2, OM-3, and OM-4
      all recognize a second glycoprotein antigen of mol. wt around 36,000. At four
      weeks after removal of the ipsilateral entorhinal cortex the background OM
      immunostaining of the entorhinal afferent zone is abolished and replaced by a
      network of densely stained granules, which we interpret as degenerating
      entorhinal afferent axons. At the same time, the proximal, IM immunoreactive zone
      expands by about 10 microns in width (while the distal deafferented zone shrinks
      by about 80 microns). Attempts were made to restore the OM immunoreactivity of
      the distal zone by grafting either small pieces or cell suspensions of embryonic
      day 18 entorhinal cortex directly into the dentate molecular layer of
      entorhinally deafferented adult hosts. About half (14/26) of the animals with
      successfully positioned grafts showed restoration of OM-2 to OM-4 immunostaining
      throughout the entire width of the outer two-thirds (entorhinal afferent zone) of
      the dentate molecular layer. Strikingly, however, in adjacent serial sections the
      restoration of OM-1 immunoreactivity was restricted to the "middle" molecular
      layer, i.e. the most proximal part of the distal (entorhinal) two-thirds of the
      dentate molecular layer. In no case did the OM-1 immunoreactivity extend to the
      outer margin of the molecular layer. This did not appear to be associated with
      incompleteness of the removal of the host entorhinal projection, since it
      occurred in grafted cases where the hippocampus had been completely isolated from
      the entorhinal area. The simplest explanation of the observed pattern of OM loss
      and restitution is that the epitopes are located on the entorhinodentate axons,
      but it is not clear whether the antigens recognized by OM-1 and OM-2 to OM-4 are
      expressed in different parts of the same group of axons, or in different subsets
      of entorhinodentate axons. Nor is it clear why the pattern of OM-1 is only
      restored to the "middle" molecular layer, while that of OM-2 to OM-4 is restored
      to the entire outer two-thirds.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375713
TI  - Long-term results of trabeculectomy with collagen sponge implant containing low
      dose antimetabolite.
AB  - Eighteen eyes of 15 patients with uncontrolled glaucoma (neovascular,
      intracapsular aphakia, uveitic, previous filtration failure) at high risk for
      failure of standard filtration underwent trabeculectomy with implantation of a
      purified collagen sponge containing 100 micrograms of antimetabolite (5
      fluorouracil or bleomycin). Follow-up ranged from 3 months to 5 years. At the end
      of follow-up, 14 eyes (78%) had intraocular pressure below 21 mmHg and functional
      filtration blebs. No corneal toxicity was encountered at any time. Two patients
      (both successes) had partial or complete erosion of the collagen sponge. Although
      the differences were not statistically significant, patients receiving bleomycin
      had better success rates (8 of 9 versus 6 of 9) and lower intraocular pressure
      levels (11.88 mmHg versus 14.63 mmHg) than those receiving 5-fluorouracil. The
      collagen sponge implant demonstrates the clear advantages of drug delivery
      devices for the administration of antimetabolites after filtration surgery.

PMID- 1375712
TI  - Hepatitis C virus infection in chronic haemodialysis patients, a
      clinicopathologic study.
AB  - Fifty-two patients on regular haemodialysis at our institution were evaluated for
      the presence of HCV infection. Evaluation included detailed history, clinical
      examination, and monthly screening for anti-HCV antibody, liver enzymes (ALT,
      AST), serum iron and ferritin. Also, three-monthly screening for other viral
      markers, HBV (HBsAg, HBsAb, HBcAb), CMV (IgG and IgM), EBV, and HIV. Anti-HCV
      antibody was found in 21 patients (40.4%). There was a significant (P less than
      0.05) relationship between presence of anti-HCV antibody and proportion of
      patients who received blood transfusion. During a 12-month follow-up, four
      (11.4%) patients seroconverted to be Anti-HCV positive while one case (4.8%)
      seroconverted to be anti-HCV negative. The frequency of elevation of liver
      enzymes was significantly higher in Anti-HCV positive cases (14/18) than in
      negative cases (11/28, P = 0.01). Evaluation of liver biopsies of 13 patients
      showed chronic persistent hepatitis in six and chronic active hepatitis in seven
      cases. We concluded that hepatitis C is a common problem among chronic
      haemodialysis patients at our institution; HCV infection is documented in 70% of
      all clinically diagnosed NANB hepatitis. Presence of anti-HCV antibodies cannot
      differentiate between active and past infection and cases with early HCV
      infection can be missed when relying on the mere detection of anti-HCV
      antibodies.

PMID- 1375714
TI  - Role of magnetic resonance imaging in the evaluation of the hydroxyapatite
      orbital implant.
AB  - The role of magnetic resonance imaging (MRI) in the assessment of fibrovascular
      ingrowth in the integrated hydroxyapatite orbital implant is evaluated. Fifteen
      patients who underwent enucleation and placement of a hydroxyapatite orbital
      implant were evaluated for degree of implant vascularity with gadolinium-DPTA
      enhanced MRI with surface coil before drilling the implant. On T1-weighted
      images, the hydroxyapatite sphere appeared with intermediate signal. After
      gadolinium-DPTA administration, all patients showed an enhancement in the implant
      consistent with the presence of fibrovascular ingrowth. The enhancement was most
      notable in the peripheral portions of the sphere and was seen as early as 5
      months after implantation. Comparison of gadolinium-DPTA-enhanced MRI with
      contrast-enhanced computed tomography, ultrasonography, and color Doppler imaging
      suggests that these latter techniques are not as helpful in the detection of the
      fibrovascular tissue in the orbital implant. Bone scan, a technique used by many
      surgeons, demonstrates fibrovascular ingrowth, but it is limited by its one
      dimensional low-resolution image. Because of its three-dimensional capability and
      its highest resolution, contrast-enhanced MRI with surface coil appears to be the
      best imaging method for evaluating the hydroxyapatite orbital implant and its
      fibrovascular ingrowth.

PMID- 1375715
TI  - Identification of the testis c-mos promoter: specific activity in a seminiferous
      tubule-derived extract and binding of a testis-specific nuclear factor.
AB  - The c-mos proto-oncogene is predominantly expressed in male and female germ cells
      and is involved in the regulation of meiosis. To investigate the mechanism of
      testis-specific regulation of c-mos transcription, I set out to identify the rat
      testis c-mos promoter. This was achieved by characterization of the rat testis c
      mos transcription start site by primer extension and sequence analysis of cDNAs
      obtained by polymerase chain reaction amplification of 5' ends of c-mos RNA. The
      rat testis c-mos transcription start site is located 0.56 kb upstream of the
      coding region. A fragment containing the rat testis c-mos promoter directs
      transcription in a nuclear extract derived from rat seminiferous tubules, but not
      in a liver nuclear extract. DNAase I footprint analysis and gel-retardation
      assays showed binding of a novel testis-specific nuclear factor to the rat testis
      c-mos promoter at a site homologous to the testis-specific cis-acting element
      identified in the promoter of the RT7 gene, which is specifically expressed in
      haploid male germ cells.

PMID- 1375716
TI  - Analysis of phosphotyrosine-containing proteins present in v-src-infected myeloid
      progenitor cells.
AB  - We examined the phosphotyrosine-containing proteins in v-src-infected myeloid
      cells. Proteins with relative molecular weights (M(r)) of 180,000, 175,000,
      135,000, 125,000, 120,000, 90,000, 75,000, and 60,000 were present in v-src
      infected but not in uninfected 32D cl3 cells. Stimulation of 32D cl3 cells with
      interleukin 3 (IL-3) resulted in the tyrosine phosphorylation of a protein of
      150,000 (M(r)), which was not phosphorylated in v-src-infected 32D cl3 cells. A
      panel of monoclonal antibodies directed against phosphotyrosine-containing
      proteins in v-src-transformed chicken embryo fibroblasts (3C4, 2A7, 2B12 and
      4F11, directed against p210, p125, p120 and p85 respectively) was used to
      characterize these substrates. We did not observe tyrosine phosphorylation of
      proteins recognized by these four monoclonal antibodies in either IL-3-stimulated
      or v-src-infected 32D cl3 cells. However, we did detect tyrosine phosphorylation
      of proteins recognized by these monoclonal antibodies in v-src-transformed NIH3T3
      cells. Tyrosine phosphorylation of GTPase-activating protein (GAP) and the GAP
      associated proteins p62 and p190 was observed in v-src-infected 32D cl3 cells.
      Stimulation of 32D cl3 cells with IL-3 does not induce phosphorylation of GAP or
      the GAP-associated proteins p62 or p190. These results suggest that substrates
      for v-src vary between different cell types.

PMID- 1375717
TI  - Angiogenic activity of the K-fgf/hst oncogene in neural transplants.
AB  - Using retrovirus-mediated gene transfer into neural transplants, we have
      expressed the human K-fgf/hst oncogene in the central nervous system. Single-cell
      suspensions of fetal rat brains were removed at embryonic days 13 and 14, exposed
      to a retroviral vector encoding the K-fgf oncogene and stereotaxically implanted
      into the caudate putamen of syngenic adult Fisher rats. Recipient animals were
      sacrificed at intervals of 6-16 months without evidence of neurological
      impairment. Mock-infected grafts showed the characteristic histopathological
      appearance of organotypically differentiated neural transplants. In contrast,
      grafts exposed to the K-fgf gene exhibited abundant capillary proliferation and
      capillary angiomas. By in situ hybridization analysis and immunohistochemistry,
      expression of K-fgf was detected in neural cells adjacent to vascular
      proliferations. Neurons and glia with abundant K-fgf transcripts were
      morphologically unaffected. In order to examine the transforming potential of the
      K-fgf gene in the nervous system, we combined retrovirus-mediated transfer of the
      K-fgf oncogene with a single transplacental exposure of the donor animals to the
      neurotropic carcinogen N-ethyl-N-nitrosourea (NEU). However, this combination of
      transforming agents did not result in tumor formation in the grafts. These
      results provide evidence for a powerful angiogenic effect of K-fgf on the
      developing brain in vivo.

PMID- 1375719
TI  - Occurrence of distinct PML-RAR-alpha fusion gene isoforms in patients with acute
      promyelocytic leukemia detected by reverse transcriptase/polymerase chain
      reaction.
AB  - A specific 'nested' reverse transcriptase/polymerase chain reaction (RT/PCR)
      procedure was used to characterize the expression patterns of PML-RAR-alpha
      chimeric mRNAs in 32 patients with acute promyelocytic leukemia (APL). The
      sensitivity of the technique was such that the fusion gene transcript could be
      detected from as little as 2.5 pg of total leukemic cell RNA against a background
      of 1 microgram of cellular RNA lacking the PML-RAR-alpha fusion gene
      transcript(s). In 19 cases the PML-RAR-alpha isoform referred to here as long was
      identified. A short isoform, which in comparison with the long form lacks three
      PML exons, was detected in 11 other cases. A third PML-RAR-alpha mRNA isoform, in
      which the most 3' PML exon present in the long-type isoform was truncated in its
      sequences lying immediately upstream of RAR-alpha B region, was found and
      characterized in a single patient. In one APL patient with a variant
      translocation t(11;17), the PCR product corresponding to PML-RAR-alpha chimeric
      mRNAs could not be amplified despite the presence of RAR-alpha gene
      rearrangement. Genomic and PCR analysis showed that the different PML-RAR-alpha
      isoforms found in APL patients arise as a result of distinct translocation
      breakpoints. In each case the exons encoding the B-F regions of RAR-alpha are
      expressed and are spliced downstream from variable PML gene exons. The 'nested'
      RT/PCR analysis of the PML-RAR-alpha fusion gene proved to be a rapid and
      sensitive tool for the diagnosis of the APL and for monitoring the residual APL
      chimeric mRNA expression during complete remission.

PMID- 1375718
TI  - Cloning and characterization of a thermolabile v-src gene for use in reversible
      transformation of mammalian cells.
AB  - The use of temperature-sensitive (ts) src mutants for studies of cell
      transformation and differentiation has been limited by the availability of cloned
      ts-src genes that are inactivated at temperatures compatible with growth of
      mammalian cells. In this report, we describe the cloning and characterization of
      the tsLA90src gene, which displays tight thermal sensitivity at 39.5 degrees C.
      Nucleotide sequence comparison of tsLA90 and wild-type src genes from the Schmidt
      Ruppin subgroup A and D strains of Rous sarcoma virus (RSV) revealed four amino
      acid differences in tsLA90src. Substitution of one of these residues (Lys-280)
      from tsLA90src with its wild-type homolog (Glu-280) caused a reversion to a wild
      type src phenotype. The cloned tsLA90 gene, designated tsUP1, was introduced into
      avian and mammalian retroviral vectors. Chicken embryo fibroblasts and
      immortalized mouse 3T3 cells infected with these viral vectors displayed a
      temperature-dependent transformed phenotype as assessed by cell morphology,
      secretion of plasminogen activator, transcriptional activation of the primary
      response genes, Egr-1 and TIS 10, and stimulation of tyrosine phosphorylation. In
      addition, chicken myoblasts (infected with RSVtsUP1) showed a temperature
      dependent differentiation into myotubes. Thus, this cloned src gene should be
      ideally suited for inducing reversible transformation and differentiation of
      mammalian cells in culture.

PMID- 1375721
TI  - Cancer pain relief by continuous administration of epidural morphine in a
      hospital setting and at home.
AB  - Fifteen patients with severe pain due to malignancy were treated by continuous
      epidural morphine infusions. A disposable external pump was used. Patients were
      treated in a hospital setting or at home for a total of 906 days. Pain intensity
      was estimated by VAS. The pumps functioned well. Bacterial growth was found in
      0.6% of the balloon reservoirs used, while the epidural filters were free from
      growth. There were no clinical infections. It appears that this delivery system
      is safe, practical and suitable for use in the home environment.

PMID- 1375722
TI  - Organic hallucinosis in patients receiving high doses of opiates for cancer pain.
AB  - We report 4 patients who developed organic hallucinosis while receiving opiate
      analgesics for cancer pain. In all patients, the symptoms rapidly responded to
      haloperidol and change in the type of opiate. The hallucinations were exclusively
      visual. Cognitive status, determined by the Mini-mental State Questionnaire
      (MMSQ), was normal in all patients. Organic hallucinosis occasionally occurs in
      patients receiving opiates and can be a major source of distress for patients and
      their families.

PMID- 1375720
TI  - Functional homology between N-myc and c-myc in murine plasmacytomagenesis:
      plasmacytoma development in N-myc transgenic mice.
AB  - Mouse plasmacytomas induced by pristane oil alone, or in combination with Abelson
      murine leukemia virus (A-MuLV), regularly carry one of three alternative
      chromosomal translocations that juxtapose c-myc to immunoglobulin heavy- or light
      chain loci. E mu-c-myc transgenic mice develop translocation-free plasmacytomas
      after induction by pristane oil and/or A-MuLV [Sugiyama, H., Silva, S., Wang, Y.,
      Weber, G., Babonits, M., Rosen, A., Wiener, F. & Klein, G. (1990). Int. J.
      Cancer, 46, 845-852]. In order to test whether another member of the myc family,
      N-myc, could play a similar role as c-myc, we treated E mu-N-myc transgenic mice
      with pristane and helper-free A-MuLV. Of 20 mice that received a single pristane
      injection followed by A-MuLV, 17 developed plasmacytomas with a mean latency
      period of 54 +/- 20 days. In a corresponding group that only received a single
      pristane injection, five out of six transgenic mice developed plasmacytomas with
      a mean latency period of 142 +/- 32 days. However, after three monthly injections
      of pristane, all 15 transgenic mice developed plasmacytomas with a mean latency
      period of 128 +/- 20 days. All plasmacytomas expressed the N-myc transgene, while
      none of them expressed either c-myc or endogenous N-myc. None of the tumors
      carried the usual plasmacytoma-associated translocations.

PMID- 1375723
TI  - Relationship between autotomy behaviour and spinal cord monoaminergic levels in
      rats.
AB  - In the rat, unilateral neurectomy of the sciatic and saphenous nerves causes
      autotomy, a self-mutilation behaviour, against the denervated limb that is
      variable in both its onset and severity. To study some of the possible
      neurochemical sources of this variability, spinal cord levels of norepinephrine
      (NE), dopamine (DA), serotonin (5-HT0 and 5-hydroxyindoleacetic acid (5-HIAA)
      were analysed ipsi- and contralateral to the lesioned side by high performance
      liquid chromatography at C5-T1 and L1-S1. According to the early or late onset
      and to the slight or intense autotomy behaviour, the animals were assigned to
      four different groups: early autotomy, early no autotomy, late autotomy, and late
      no autotomy. Two sham-operated groups were sacrificed at an early or late stage
      in the postoperative period. The spinal cord NE content remained unchanged
      throughout the different experimental situations. The more conspicuous changes
      observed were: (1) a generalized increase in spinal 5-HT metabolism in all
      deafferented groups; (2) a significant and selective increase in lumbosacral 5-HT
      and 5-HIAA levels of the rats that did not self-lesion for 8 weeks after
      deafferentation and (3) a significant fall (30-45%) in DA levels at denervated
      spinal segments of the rats that actively self-attacked late in the postoperative
      period. The data suggests that spinal cord serotonergic and dopaminergic
      influences play an important role in determining the susceptibility to autotomy
      (and perhaps chronic pain) after peripheral deafferentation.

PMID- 1375724
TI  - Do opioids evoke the release of serotonin in the spinal cord? An in vivo
      microdialysis study of the regulation of extracellular serotonin in the rat.
AB  - This study investigated the regulation of serotonin (5-HT) and its major
      metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the dorsal spinal cord of
      awake, freely moving rats, using microdialysis coupled to HPLC with
      electrochemical detection and tested the hypothesis that opioids exert their
      analgesic effect in part through the increased release of 5-HT in the dorsal
      horn. A dialysis tube was placed transversely at the L4 segment of the dorsal
      spinal cord and the basal concentration of 5-HT in the dialysate was
      characterized by infusion of a variety of substances through the dialysis probe:
      tetrodotoxin (TTX), KCl, imipramine, fluoxetine and amphetamine (AMPH). To
      evaluate the contribution of opioids, we also studied the effects of either
      systemic or intracerebroventricular (i.c.v.) injection of morphine or DAMGO.
      Extracellular concentrations of 5-HT and 5-HIAA were partially and reversibly
      reduced by TTX. In the presence of KCl, imipramine, fluoxetine or AMPH, 5-HT
      levels significantly increased. Under these conditions, extracellular 5-HIAA
      levels usually decreased. By contrast, the effects of opioids on 5-HT
      concentrations were highly variable. Low doses of morphine administered
      systemically increased 5-HT concentrations in only 3 of 6 rats. This was
      paralleled by a decrease in 5-HIAA. Higher doses of morphine, alone or in the
      presence of fluoxetine, did not change 5-HT concentrations.
      Intracerebroventricular injection of morphine or DAMGO increased the
      extracellular concentrations of 5-HT in only about one third of the animals.
      After intracerebroventricular opioid injection, extracellular concentrations of 5
      HIAA either decreased by about 20% or did not change.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1375725
TI  - Epidural opiates and local anaesthetics for the management of cancer pain.

PMID- 1375726
TI  - Comments on Marchand et al., PAIN, 45 (1991) 249-257.

PMID- 1375727
TI  - Effect of exposure to sauna heat on neuropathic and rheumatoid pain.
AB  - Exposure to sauna heat during sauna bathing raises the skin temperature of the
      bather near the hot pain perception threshold and enhances sympathetic activity.
      Self-reports provided by regular bathers of changes in intensity of their ongoing
      pain might, therefore, add novel information on the effect of intense heat on
      various pain conditions. We interviewed consecutive patients attending our pain
      clinic over a period of 1 year about their pain-related responses to sauna
      bathing and controlled the results by quantitated somatosensory tests. There were
      61 patients with chronic neuropathic pain of peripheral origin, 13 patients with
      central pain and 59 patients with rheumatoid pain. Allodynia and hyperalgesia to
      heat were relatively infrequent in all groups (10%, 15% and 8%, respectively).
      Three out of 17 patients with postinjury nerve pain reported similar
      exacerbation. By contrast, mechanical allodynia was present in 48% of patients
      with peripheral neuropathic pain and in 54% of patients with central pain. The
      results speak against an important role for C-afferent or sympathetic
      postganglionic fibres in most subclasses of neuropathic pain. Animal models of
      neuropathic pain should be critically viewed against this finding.

PMID- 1375728
TI  - Individual variability in the response to different opioids: report of five
      cases.
AB  - Although it is widely appreciated that patients can demonstrate highly variable
      responses to different opioid drugs, there have been few detailed descriptions of
      this phenomenon. To illustrate this variability, we present 5 patients, 4 with
      cancer pain and 1 with non-malignant pain, who underwent dose titration with more
      than 1 opioid and developed markedly different responses to each. In every case,
      dose escalation led to successful treatment with 1 opioid and to intolerable side
      effects without adequate relief with others. The existence of this individual
      variability in the response to different opioids has important implications for
      both clinical practice and current understanding of opioid pharmacology in man.
      It contradicts the view that any opioid is inherently more efficacious than any
      other, suggests that patients who fail to obtain adequate pain relief at
      maximally tolerated doses of 1 opioid may benefit from an alternative drug, and
      underscores the potential importance of genetic factors as a determinant of
      opioid response.

PMID- 1375729
TI  - Tumor necrosis factor-alpha in human milk.
AB  - We previously demonstrated that certain biologic activities in human milk were
      partially blocked by antibodies directed against human tumor necrosis factor
      alpha (TNF-alpha). In this study, immunochemical methods were used to verify the
      presence of TNF-alpha in human milk obtained during the first few days of
      lactation. Gel filtration revealed the presence of TNF-alpha by RIA in molecular
      weight fractions between 80 and 195 kD. TNF-alpha could not be detected
      consistently by conventional Western blotting or cytotoxic assays. Although
      immunoreactive bands were detected by a Western blot-125I protein A technique in
      TNF-alpha-positive fractions from gel filtration, those bands proved to be
      nonspecific. TNF-alpha in milk was reliably quantified by the competitive RIA.
      Those studies revealed that the concentrations of TNF-alpha in milk were 620 +/-
      183 pg/mL. Although RNA to TNF-alpha was detected in milk leukocytes by Northern
      blotting, little TNF-alpha was found in those cells before or after stimulation
      with N-formyl-l-methionyl-l-leucyl-l-phenylalanine or 4 beta-phorbol-12 beta
      myristate-13 alpha-acetate. The origin of this cytokine in human milk remains
      unclear. Nevertheless, this study suggests that TNF-alpha is present in early
      human milk in sufficient quantities to exert possible biologic effects upon the
      mammary gland of the mother or the immune system of the infant.

PMID- 1375730
TI  - Increased red cell aggregation does not reduce uteroplacental blood flow in the
      awake, hemoconcentrated, late-pregnant guinea pig.
AB  - The effect of increased red blood cell aggregation on uteroplacental blood flow
      was studied in 11 awake, late-pregnant guinea pigs. The aggregation of the red
      cells was increased by administering high molecular weight dextran (HMWD) to the
      previously hemoconcentrated animal. The purpose of the hemoconcentration before
      HMWD was 1) to use a preeclampsia model in which the hemorheology may be impaired
      because of the combined effect of polycythemia, an increased red cell
      aggregation, and an increased plasma viscosity and 2) to potentiate the
      aggregation-increasing effect of HMWD. Relative to the pre-HMWD condition,
      arterial blood pressure and systemic vascular resistance increased by 10 and 26%,
      respectively. The cardiac output fraction shunted across the systemic circulation
      and the arterial hematocrit decreased by 30 and 4%, respectively. Neither cardiac
      output nor the weighted organ flows, including those to the placentas, changed in
      response to the rise in red cell aggregation. We conclude that an imposed
      increase in red cell aggregation has no appreciable effect on uteroplacental
      blood flow in the awake and healthy late-pregnant guinea pig. These data do not
      exclude the possibility that increased red blood cell aggregation potentiates the
      negative effects on uteroplacental blood flow, e.g. in pregnancy-induced
      hypertension or preeclampsia, where the placenta is not only marginally perfused
      but also frequently damaged histologically.

PMID- 1375731
TI  - Enhancing the cognitive outcomes of low birth weight, premature infants: for whom
      is the intervention most effective?
AB  - The Infant Health and Development Program is a national collaborative study to
      test the efficacy of combining early child development and family support
      services with pediatric follow-up to reduce the incidence of health and
      developmental problems among low birth weight, preterm infants in eight medical
      school sites. Its efficacy in enhancing intellectual outcomes at age 3 in more
      and less environmentally vulnerable, low birth weight, preterm children, as
      defined by maternal education (high school completion or less vs some college)
      and race (black vs white/other), is explored. Children whose mothers had a high
      school education or less benefited from the intervention. This was true for both
      the black and white samples. Children whose mothers had attended college did not
      exhibit significant enhancement in IQ scores at 3 years. Birth weight affected
      the response to treatment for one of the four subgroups: Among white mothers with
      some college, the lighter (less than 2000 g) low birth weight, preterm children
      were less influenced by the intervention than were the corresponding heavier
      children. Implications for targeting certain subgroups of low birth weight,
      preterm children for services are considered.

PMID- 1375732
TI  - Accuracy of the Denver-II in developmental screening.
AB  - One of the oldest and best known developmental screening tests was recently
      restandardized and revised as the Denver-II. Because it was published without
      evidence of its accuracy, the present study was undertaken with 104 children
      between 3 and 72 months of age attending one of five day-care centers. To
      determine the presence of developmental problems, children were administered
      individual measures of intelligence, speech-language, achievement, and adaptive
      behavior. A second psychological examiner, blind to the outcome of the diagnostic
      battery, administered the Denver-II. Developmental problems including language
      impairments, learning disabilities, mild mental retardation, and/or functional
      developmental delay were found in 17% of the children. The Denver-II identified
      correctly 83% and thus had high rates of sensitivity. However, more than half the
      children with normal development also received abnormal, questionable, or
      untestable Denver-II scores. Thus the test had limited specificity (43%) and a
      high overreferral rate. The alternative scoring method, categorizing
      questionable/untestable scores as normal, caused sensitivity to drop to 56%
      although specificity rose to 80%. Since neither scoring method produced
      acceptable levels of accuracy, an effort was made to locate the sources of
      accuracy and inaccuracy within the test. Only items in the language domain were
      modestly helpful in discriminating children with and without difficulties. The
      findings suggest that the authors of the Denver-II need to engage in further
      development of the instrument including revising scoring criteria and item
      placement in relation to children's ages. In the interim, test users should
      employ screening tests which are more accurate such as the Minnesota Inventories
      or the Battelle Developmental Inventory Screening Test.

PMID- 1375733
TI  - Developmental screening: (still) expecting the impossible?

PMID- 1375734
TI  - Poisoning by pickup truck.

PMID- 1375735
TI  - The T-loop region of animal mitochondrial tRNA(Ser)(AGY) is a main recognition
      site for homologous seryl-tRNA synthetase.
AB  - Recognition sites of bovine mitochondrial serine tRNA specific for condons AGY
      [tRNA(Ser) (AGY)] by the cognate mitochondrial seryl-tRNA synthetase were studied
      using a range of tRNA(Ser)(AGY) variants which were obtained by the in vitro
      transcription of synthetic tRNA genes with T7 RNA polymerase. Base replacements
      in the anticodon and discriminator sites did not affect serine acceptance.
      However, deletion and/or replacement in the T-loop region completely deprived the
      variants of their charging activities. Point mutation experiments in this region
      also showed that the adenosine residue in the middle of the T-loop (position 58),
      which is involved in tertiary interaction between the T-loop and the truncated D
      arm [de Bruijn and Klug, 1983] played a significant role in the recognition
      process by the synthetase.

PMID- 1375737
TI  - Mutational evidence for competition between the P1 and the P10 helices of a
      mitochondrial group I intron.
AB  - A guanosine to cytosine transversion at position 2 of the fifth intron of the
      mitochondrial gene COB blocks the ligation step of splicing. This mutation
      prevents the formation of a base pair within the P1 helix of this group I intron-
      the RNA duplex formed between the 3' end of the upstream exon and the internal
      guide sequence. The mutation also reduces the rate of the first step of splicing
      (guanosine addition at the 5' splice junction) while stimulating hydrolysis at
      the 3' intron-exon boundary. Consequently, the ligation of exons is blocked
      because the 3' exon is removed prior to cleavage at the 5' splice junction. The
      lesion can be suppressed by second-site mutations that preserve the potential for
      base-pairing at this position. Because the P1 duplex and the P10 duplex (between
      the guide sequence and the 3' exon) overlap at the affected pairings represent
      alternative structures that do not, indeed cannot, form simultaneously.

PMID- 1375738
TI  - Nucleotide sequences of ten mitochondrial tRNA genes in yeast Hansenula wingei.

PMID- 1375736
TI  - In vitro study of E.coli tRNA(Arg) and tRNA(Lys) identity elements.
AB  - Various tRNA transcripts were constructed to study the identity elements of
      E.coli tRNA(Arg) and tRNA(Lys). Exchange of the anticodon of the major tRNA(Arg)
      from ACG to either CCG or CCU did not result in a significant loss of arginine
      acceptor activity, whereas not only that to UUU but also that to ACA or ACC
      decreased the activity. Base substitutions and deletion at A20 also impaired the
      arginine charging activity by over 50-fold. Arginine charging activity was
      introduced by either substitution of the anticodon from UAC to ACG in tRNA(Val)
      or from UUU to UCU in tRNA(Lys). Only a single base substitution at the third
      position of tRNA(Trp) anticodon (CCA) from A to G also gave rise to arginine
      charging activity, which was elevated to a comparable level to that of the
      tRNA(Arg) transcript by an additional A20 insertion. Base substitutions of the
      major tRNA(Arg) at the discriminator position into pyrimidines led to a decrease
      by factors of three to four. These data show that the third letter of the
      anticodon G36 or U36 besides the second letter C35 and the A20 in the variable
      pocket is responsible for the arginine acceptor identity, to which the
      discriminator base A73 or G73 contributes in an auxiliary fashion. In contrast to
      the arginine system, the transcript with the wild-type tRNA(Lys) sequence showed
      only 140-fold lower lysine charging activity than the native tRNA(Lys),
      suggesting the involvement of base modifications in recognition. Replacement of
      the anticodon UUU with not only UCU and UAC but also UUA and UUC seriously
      affected the lysine acceptor activity, and those with GUU and UUG also decreased
      by factors of 17 and 5, respectively. Introduction of UUU into the anticodons
      conferred lysine charging activity upon both tRNA(Val) and tRNA(Arg).
      Substitution of the discriminator base A73 by any of the other bases decreased
      the lysine acceptor activity by a factor of ten. These results indicate the
      involvements of all the three bases of the anticodon and A at the discriminator
      position in lysine specific aminoacylation.

PMID- 1375739
TI  - An efficient method for isolation of RNA and DNA from plants containing
      polyphenolics.

PMID- 1375740
TI  - Flow cytometry: an overview.
AB  - Flow cytometry is a method of rapidly analyzing large numbers of cells as they
      flow in a liquid medium through a laser source. Flow cytometry provides valuable
      information regarding DNA content, RNA content, and the percentage of cells in
      the S phase of the cell cycle. This information can be used to predict the
      aggressiveness of many tumors, which has direct prognostic and diagnostic
      implications. Flow cytometry assists healthcare professionals in planning and
      implementing effective, appropriate, and timely interventions. Because flow
      cytometry is becoming more prevalent, nurses must be aware of its actual and
      potential applications. The data obtained from flow cytometry provide important
      information that can assist nurses in anticipating a particular regimen for
      specific tumors and in projecting the patient's clinical course. With this
      information, nurses can modify and individualize care plans. When used in
      conjunction with a patient's clinical presentation and other laboratory findings,
      flow cytometry has a direct impact on both treatment decisions and nursing
      interventions.

PMID- 1375741
TI  - Cardiac myxoma with a cytokeratin-immunoreactive glandular component.
AB  - This study documents the expression of cytokeratin intermediate filaments (IFs)
      in a surgically excised glandular atrial myxoma. The glandular structures showed
      also positivity for carcinoembryonic antigen. Typical isolated or cordlike myxoma
      cells contained vimentin IFs. Positivity for von Willebrand factor was detected
      in cells lining deep invaginations of surface papillae and vascular channels.
      Bundles of smooth muscle cells and myofibroblasts scattered throughout the myxoid
      matrix synthesized the isoform of alpha-actin specific for smooth muscle.

PMID- 1375742
TI  - A monoclonal antibody that recognizes a formalin-resistant epitope on the p 24
      core protein of HIV-1.
AB  - A murine monoclonal antibody (called H-11) that binds to the p 24 core protein of
      HIV-1 was characterized by radioimmuno-precipitation, immunofluorescence, western
      blot assays, immunocytochemistry and immunohistochemistry. This antibody was
      found to be especially suited for demonstrating the presence of HIV-1 in formalin
      fixed, paraffin-embedded tissues.

PMID- 1375743
TI  - Correlated responses in lines of chickens divergently selected for fifty-six-day
      body weight. 2. Organ growth, deoxyribonucleic acid, ribonucleic acid, and
      protein content.
AB  - Growth of organs relative to body weight and cellular protein, RNA, DNA, and cell
      unit size of breast muscle, liver, and small intestinal tissue were measured in
      females from four lines of chickens. Two lines had undergone 32 generations of
      divergent selection for 56-day body weight, and the other two lines were derived
      by sampling the first two lines at Generation 28 and relaxing selection for the
      next five generations. The diet used in the present experiment was the same diet
      under which selection was practiced (20% crude protein and 2,685 kcal of ME/kg).
      Comparisons at common chronological ages and a common body weight revealed that
      supply organ weights, especially that of the small intestine, were associated
      with subsequent growth of demand organs. Although the upper gastrointestinal
      tract was also important in this respect, it was more susceptible to influences
      such as feed intake. Selection for juvenile body weight resulted in correlated
      changes in cell size of breast muscle but not liver and small intestine. Muscle
      increased posthatch as cells underwent hypertrophy but liver and small intestine
      grew chiefly by hyperplasia.

PMID- 1375744
TI  - Correlated responses in lines of chickens divergently selected for fifty-six-day
      body weight. 3. Digestive enzymes.
AB  - Levels of amylase, trypsin, chymotrypsin, and lipase in the pancreas and small
      intestinal chyme were measured in females from four lines of chickens. Two of the
      lines had undergone 32 generations of divergent selection for 56-day body weight,
      and in the other two lines selection for high or low weight had been relaxed for
      5 generations. The diet used in the present experiment was that under which
      selection had been practiced (20% crude protein and 2,685 kcal of ME/kg).
      Comparisons between divergently selected lines at common ages revealed higher
      enzyme levels for high- than low-weight lines. When comparisons were made at a
      common body weight (80 +/- 5 g) there were no differences between lines. These
      results suggested that correlated responses in feed intake were mediating the
      regulation of digestive enzyme levels in the pancreas and in intestinal chyme of
      growth-selected lines of chickens. Chicks from high-weight lines had elevated
      enzyme levels after a mild feed restriction compared with those provided ad
      libitum access to feed. It was hypothesized that hyperphagia associated with the
      high-weight lines in combination with a mild feed restriction and the associated
      meal feeding stimulated synthesis and secretion of digestive enzymes.

PMID- 1375746
TI  - [Interaction of ovomucoid from duck egg proteins with aldehydes-dextrans].
AB  - The interaction of ovomucoid proteinase inhibitor prepared from duck egg white
      with a dextran of a molecular weight of 70,000 preliminary treated with potassium
      periodate. Irrespective of the number of the sites of the ovomucoid binding to
      aldehyde-dextran the anti-chymotryptic activity is equal to that of the native
      inhibitor, while the antitryptic activity decreases proportionally to the number
      of ovomucoid amino groups involved in the reaction with dextran. When a few
      ovomucoid molecules are immobilized on the polysaccharide macromolecule the
      perturbing effect of the protein-protein interactions is minimal, as the rigid
      polymeric chain prevents from the formation of associates of proteins immobilized
      on this backbone.

PMID- 1375745
TI  - Plasma cells expressing immunoglobulins M and A but not immunoglobulin G develop
      an intimate relationship with central canal epithelium in the harderian gland of
      the chicken.
AB  - In the Harderian gland of the chicken, the epithelial and plasma cell
      relationships were studied by light and electron microscopy and
      immunohistochemical methods. In the wall of the central canal a dark epithelial
      cell was identified that had long branching cell processes. An anticytokeratin
      monoclonal antibody demonstrated that the dark cells provided an extremely large
      contact area for the plasma cells. Although IgM-, IgG-, and IgA-producing plasma
      cells were present in the Harderian gland, only IgM- and IgA-positive cells were
      capable of a distinct relationship with dark epithelial cells. The surface of the
      primary branches contained scattered IgA deposits whereas the epithelial cells of
      the secondary branches possessed IgA along the lateral cell membrane but not on
      the surface. Anti-IgA and anti-cytokeratin antibodies produced a similar staining
      pattern in the acini and secondary branches. Taken together, these observations
      suggest that IgA secretion is a function of secondary branches and that
      intracellular transport is influenced by the cytoskeletal system.

PMID- 1375747
TI  - Generation and possible significance of trypsinogen activation peptides in
      experimental acute pancreatitis in the rat.
AB  - Trypsinogen activation peptides (TAP) were quantified by radioimmunoassay in
      blood, urine, and peritoneal exudate of rats with experimental pancreatitis.
      Forty-four animals were studied, comprising a control group and four different
      induction techniques (cerulein, cerulein plus either 2- or 10-min intraductal
      glycodeoxycholic acid [GDOC] infusion, and cerulein plus intraductal GDOC with
      enterokinase [EK]). Significantly higher TAP concentrations were found at 6 h (or
      at death) in plasma and ascites of all pancreatitis groups compared with
      controls. TAP quantitation in hourly urine samples demonstrated significantly
      higher concentrations from the third hour onward in the most severe groups and
      from the fourth hour onward in the cerulein-treated rats. All nonsurviving rats
      had a plasma TAP of greater than 2.5 nM/L, whereas only 1 of 34 surviving animals
      had such a concentration (p less than 0.001). A significant stepwise increase in
      total TAP in ascites was found when comparing the cerulein group, the two GDOC
      groups, and the EK group (p less than 0.001). Chromatography of samples with a
      high TAP content demonstrated comigration with synthetic TAP. We conclude that
      free TAP are present in blood, urine, and peritoneal exudate of rats with
      experimental pancreatitis of different pathogenesis and that the amount of TAP
      may be indicative of the severity of the disease process.

PMID- 1375748
TI  - Endocrine and exocrine function of pancreatic fragments autotransplanted into
      hepatic parenchyma.
AB  - We studied the use of hepatic parenchyma as a recipient site for pancreatic
      fragment transplantation. Endocrine and exocrine pancreatic functions were
      evaluated following pancreatic autotransplantation in 26 mongrel dogs that had
      undergone total pancreatectomy. The endocrine function of the pancreatic tissue
      transplanted to hepatic parenchyma was significantly inferior to that of normal
      controls. Cholecystic bile amylase concentrations were markedly elevated in six
      dogs that had been implanted with pancreatic fragments in their hepatic
      parenchyma and had survived more than 2 months. Also, choledochal bile amylase
      concentrations increased significantly following pancreozymin-secretion (PS)
      injection. In contrast, cholecystic bile amylase concentrations in normal dogs
      were low and choledochal bile amylase concentrations did not respond to a PS
      load. Histological examination of pancreatic autografts in hepatic parenchyma
      revealed marked proliferation of exocrine tissue with abundant zymogen granules
      and reconstruction of pancreatic lobules with a few islets.

PMID- 1375749
TI  - Formation of pseudoislets from human pancreatic cultures.
AB  - We have successfully developed a technique for culturing human islet cells
      obtained from the cadaveric pancreata of children. Within 24-48 h of in vitro
      culture, collagenase-digested human pancreatic tissue formed epithelioid
      monolayers. Scattered within these monolayers were insulin-positive cells, as
      detected by immunocytochemical and dithizone staining. Treatment of the beta cell
      containing epithelioid-cell monolayers with EDTA resulted in the formation of
      spherical cellular clusters, i.e., pseudoislets. These pseudoislets differed from
      isolated islets of Langerhans in that they showed a more peripheral distribution
      of insulin-positive cells. Our studies have demonstrated that insulin-positive
      cells can be detected in monolayers obtained from human pancreata 3-4 weeks after
      culture. When exposed to varying concentrations of glucose, these cells secreted
      insulin. The development of this in vitro technique for culturing human
      pancreatic islet tissue could provide a model for systematically studying in
      vitro islet function.

PMID- 1375750
TI  - A preliminary 3-D model of the tertiary fold of the polymerase domain of HIV-1
      reverse transcriptase.
AB  - Development of a 3-D model of the reverse transcriptase from type 1 human
      immunodeficiency virus (HIV-1 RT), a key enzyme in the pathogenesis of the virus,
      presents a significant challenge. Three-dimensional structural information is not
      available for any close homolog, the only 3-D structural data being that of the
      Klenow fragment (KF) of Escherichia coli DNA polymerase I, for which coordinates
      of only the alpha-carbons are available. A recently published study of the
      sequences of a large number of polymerases led to the identification of three
      common sequence patterns, nominally motif A, motif B and motif C, and to the
      hypothesis that the various DNA and RNA polymerases including E. coli DNA
      polymerase I and HIV-1 RT share a common structural motif around their respective
      polymerase active sites. The preliminary results of recent structural studies on
      two other polymerases also support this hypothesis. Based on the assumption of
      structural homology in the active site regions of their polymerase domains, the
      HIV-1 RT and KF sequences were aligned using pattern-based secondary structure
      predictions as a guide and motifs A, B and C as 'anchor points'. However, as
      suggested by the results of chemical modification experiments, it was assumed
      that the order of the motifs in KF, viz. A, B and C, differed from that of the
      related motifs A, C and B' in HIV-1 RT, a rearrangement that could have been
      brought about by an exon shuffling type of mechanism.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1375751
TI  - Heat capacity changes and hydrophobic interactions in the binding of FK506 and
      rapamycin to the FK506 binding protein.
AB  - Differential interactions among nonpolar moieties at protein/ligand interfaces,
      and of these nonpolar groups with water, collectively termed hydrophobic
      interactions, are widely believed to make important energetic contributions to
      the stability of protein/ligand complexes. Quantitative estimates of hydrophobic
      interactions, and an evaluation of their structural basis, are essential for
      obtaining structure-based predictions of the free energies of binding for the
      purpose of drug design. Two largely nonpolar, immunosuppressive agents, FK506 and
      rapamycin, each bind with high affinity to a common hydrophobic pocket on a small
      peptidylproline cis-trans isomerase known as FK506 binding protein (FKBP-12) and
      inhibit its activity. In an effort to elucidate the structural features of these
      ligands responsible for the observed energetics, we have undertaken an
      investigation of the thermodynamics of binding of FK506 and rapamycin to FKBP-12.
      Enthalpies of binding have been determined by high-precision titration
      calorimetry over a range of temperature, allowing estimates of heat capacity
      changes. By analyzing the distribution of changes in solvent-accessible surface
      area upon binding of FK506 to FKBP-12 from crystallographic data, it is found
      that 99% of the net surface buried upon binding involves nonpolar groups. This
      leads to a heat capacity change of FK506 binding, normalized to the amount of
      nonpolar surface, of -0.40 +/- 0.02 cal.K-1.mol-1.A-2 (1 cal = 4.18 J), a value
      similar to that obtained for the aqueous dissolution of hydrophobic substances.
      Our observations are discussed in view of the general nature of hydrophobic
      interaction processes.

PMID- 1375752
TI  - Purified unitary kainate/alpha-amino-3-hydroxy-5-methylisooxazole-propionate
      (AMPA) and kainate/AMPA/N-methyl-D-aspartate receptors with interchangeable
      subunits.
AB  - We have purified and characterized two vertebrate excitatory amino acid
      ionotropic receptors from the Xenopus central nervous system. Each is a unitary
      receptor (i.e., having more than one class of excitatory amino acid agonist
      specificity within one protein oligomer). The first is a unitary non-N-methyl-D
      aspartate (non-NMDA) receptor and the second is a unitary NMDA/non-NMDA receptor.
      The specific agonist-activated channel activity and pharmacology of each type
      were recognized by patch-clamping lipid bilayers in which the isolated protein
      was reconstituted. In the second case, the NMDA and the non-NMDA sites could not
      be physically separated and exhibited functional interaction. Parallel evidence
      for this was obtained when poly(A) RNA from Xenopus brain was translated in
      oocytes: a noncompetitive inhibition of the response to L-kainate is produced by
      NMDA to a maximum depression of 30% at 1 mM NMDA. Each isolated oligomer contains
      42-kDa subunits of the non-NMDA ligand binding type, but the second type has an
      additional NMDA-receptor-specific 100-kDa subunit. Thus, a subunit-exchange
      hypothesis can account for the known multiplicity of excitatory amino acid
      receptor types.

PMID- 1375753
TI  - Translocation of spectrin and protein kinase C to a cytoplasmic aggregate upon
      lymphocyte activation.
AB  - We have previously reported that mammalian tissue lymphocytes exhibit significant
      heterogeneity with respect to the subcellular distribution of spectrin and that
      this phenomenon may result from a dynamic behavior of spectrin in response to
      activation signals. Here, we further characterize the involvement of spectrin in
      lymphocyte activation by examining its relationship with protein kinase C (PKC).
      PKC isoenzymes are a family of cytosolic kinases that translocate from the
      soluble to particulate fraction upon cell stimulation. It is reported here that
      activation of lymph node T cells through the antigen-specific receptor, or direct
      activation of PKC by phorbol esters, results in a striking increase in cells
      expressing a cytoplasmic aggregate of spectrin. Additionally, a concurrent
      increase in cells expressing aggregates of the beta II isozyme of PKC is
      observed. Immunofluorescence staining revealed that spectrin and PKC beta II are
      colocalized in untreated lymphocytes and that these two proteins are coincidently
      translocated to the same focal aggregate within the cytoplasm following
      stimulation. This redistribution of spectrin and PKC beta is blocked by
      pretreatment with calphostin C, a specific inhibitor of PKC. Solubility studies
      showed that there is an increase of both proteins in the detergent-insoluble
      fraction of lymphocytes upon activation, and immunoprecipitation studies
      indicated that the soluble form of these molecules may be associated directly or
      indirectly as part of a complex of proteins. These data indicate that the
      positioning of the spectrin-based cytoskeleton is sensitive to activation signals
      and may play a role in the function or positioning of PKC beta II.

PMID- 1375754
TI  - Two types of anion channel currents in guard cells with distinct voltage
      regulation.
AB  - Transpirational water loss by plants is reduced by closing of stomatal pores in
      the leaf epidermis. Anion channels in the plasma membrane of guard cells may
      provide a key molecular mechanism for control of stomatal closing in leaves.
      However, central questions regarding the regulation, diversity, and function of
      anion channels in guard cells and other higher plant cells remain unanswered. We
      show here that two highly distinct types of depolarization-activated anion
      currents operate in the plasma membrane of Vicia faba guard cells. One described
      type of anion channel was activated rapidly within 50 ms by depolarization,
      inactivated during prolonged stimulation, and deactivated rapidly at
      hyperpolarized potentials (R-type anion current). The other depolarization
      activated anion current showed extremely slow voltage-dependent activation and
      deactivation (S-type anion current) and lacked inactivation. The distinct voltage
      and time dependencies of R-type and S-type anion channels suggest that they may
      play a role during depolarization-associated signal transduction in higher plant
      cells and that these anion channels may contribute to different processes in the
      regulation of stomatal movements. In particular, the slow and sustained nature of
      S-type anion channel activation revealed here leads us to hypothesize that S-type
      anion channels may provide a central molecular mechanism for control of stomatal
      closing, which is accompanied by long-term anion efflux and depolarization.

PMID- 1375755
TI  - Higher order interactions in 23s rRNA.
AB  - An alignment of 75 phylogenetically diverse large subunit ribosomal RNA sequences
      was created and searched for secondary and tertiary structure elements by
      computer. The search revealed four unknown secondary structural pairings, two
      internal loop closings, and five short-range tertiary interactions--two of which
      were pairings of an unusual type. One brings a loop together with two other loops
      previously known to be paired, and one involves a nucleotide within a presumed
      tetraloop. The latter interaction constrains the RNA structure near the ribosomal
      E-site, where two base pairs previously suggested to be in parallel orientation
      are now proven. No clear phylogenetic evidence for direct base pairing between
      the large and small subunit rRNA was found.

PMID- 1375756
TI  - Interleukin 6: insights to its function in skin by overexpression in transgenic
      mice.
AB  - Interleukin 6 (IL-6) is a cytokine that mediates a wide range of inflammatory and
      immune responses. Its expression is elevated in inflammatory or immunodeficient
      diseases, including psoriasis, rheumatoid arthritis, and AIDS. To explore the
      role of IL-6 in skin, we utilized a human keratin 14 (K14) promoter to express IL
      6 in the basal cells of stratified squamous epithelia of transgenic mice. Mice
      expressing the K14-IL-6 transgene were smaller than normal and exhibited retarded
      hair growth. Surprisingly, IL-6 expression did not lead to enhanced epidermal
      proliferation, but it did result in a thicker stratum corneum, with an otherwise
      seemingly normal program of differentiation. IL-6 expression did not lead to
      leukocytic infiltration, making it unlikely that it has direct proinflammatory
      activity in skin. Based on this study, one role of IL-6 relevant to host defense
      may be to enhance the stratum corneum, thereby providing increased protection
      from injurious stimuli or infection. If IL-6 plays additional roles in the skin,
      it is likely to act synergistically with factors that IL-6 alone cannot induce.

PMID- 1375757
TI  - Spinal neurons exhibiting a specific nociceptive response receive abundant
      substance P-containing synaptic contacts.
AB  - Substance P has been implicated in nociceptive transmission in the spinal cord.
      However, evidence for a direct correlation between a specific nociceptive
      response in spinal dorsal horn neurons and substance P input is lacking. In this
      study, we combine intracellular recording from dorsal horn neurons in vivo,
      characterization of their nociceptive responses, intracellular labeling by
      injection of horseradish peroxidase, and immunocytochemical demonstration of
      substance P at the electron microscopic level. The results reveal that dorsal
      horn neurons that respond to noxious cutaneous stimulation with a slow, prolonged
      excitatory postsynaptic potential receive a preferentially high number of
      substance P fibers compared with nonnociceptive neurons, which scarcely receive
      any substance P input. Therefore, this study provides direct evidence of a
      structural-functional link for a substance P-mediated nociceptive response.

PMID- 1375759
TI  - Urinary indoleamines in Tourette syndrome patients with obsessive-compulsive
      characteristics.
AB  - Tourette syndrome patients with high levels of obsessive-compulsive symptoms were
      compared with patients without these symptoms on urinary measures of serotonin
      and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA). Both groups were
      compared with normal controls, and it was hypothesized that patients with
      obsessive-compulsive symptoms would have lower levels of serotonin. Both groups
      of Tourette syndrome patients had lower levels than controls, but there was no
      difference between them. Obsessive symptoms were related to higher levels of
      5HIAA and to a higher turnover of serotonin.

PMID- 1375761
TI  - Crystallographic studies of a transmembrane ion channel, gramicidin A.

PMID- 1375760
TI  - Feasibility of interactive videodisc technology to teach minority youth about
      preventing HIV infection.
AB  - Hispanic and African American adolescents are more likely than white Anglo youth
      to harbor misconceptions about acquired immunodeficiency syndrome (AIDS) and are
      also more likely to engage in intravenous drug use and sexual intercourse. This
      paper describes the development of an AIDS prevention curriculum that uses an
      interactive videodisc program to teach skills for interventions. Focus group and
      expert panel studies yielded suggests for intervention vignettes and scenes
      relevant to Hispanic and African American adolescents. The authors then developed
      and produced a sample curriculum, specifically designed for Hispanic youth.
      Content was designed to build knowledge, attitudes, and skills in handling
      situations where young persons are at risk for human immunodeficiency virus (HIV)
      infection. The feasibility of the finished pilot product was tested with
      adolescents and with professionals who serve ethnic and racial minority youth.
      Adults and Hispanic adolescent viewers rated the videodisc as enjoyable,
      interesting, and likely to achieve positive effects with the intended target
      population. Findings suggest that the interactive videodisc is a useful way to
      interest and help Hispanic adolescents learn ways of reducing their risk of
      contracting and spreading HIV infection through lifestyle practices. This
      developmental research in the use of interactive videodisc also provides a basis
      for further investigation.

PMID- 1375758
TI  - Characterization of immortal cystic fibrosis tracheobronchial gland epithelial
      cells.
AB  - Tracheobronchial glands were isolated and cultured from a patient with cystic
      fibrosis (CF). Cultured epithelial cells were transformed with pSVori-. All
      transformed cell lines express cytokeratin filaments and at early passages
      express the junctional complex molecule cell CAM 120/80, indicating their
      epithelial origin. Several gland cell lines express antigens that localize to
      secretory cells in vivo. Cl- transport measured by 36Cl efflux shows that CF
      gland epithelial cells, like CF surface airway and nasal polyp epithelial cells,
      are unable to respond to increases in intracellular cAMP. However, they do
      produce an increase in intracellular cAMP after treatment with isoproterenol or
      forskolin. One CF gland cell line shows increased intracellular calcium in
      response to a number of agents and increased Cl- efflux comparable to that
      observed in a non-CF airway surface epithelial cell line after addition of
      calcium ionophore. All cell lines express CF transmembrane conductance regulator
      mRNA, as measured by PCR amplification of first-strand cDNA. The CF
      tracheobronchial gland cell lines described here are compound heterozygotes,
      having a single copy of the delta F508 mutation.

PMID- 1375762
TI  - [Increase in the pulmonary toxicity of bleomycin caused by the FiO2].

PMID- 1375764
TI  - Desensitization to vasopressin action in the rat kidney medulla: studies on
      isolated nephron segments.
AB  - Because of the prominent role of the renal medulla in the elaboration of
      concentrated urine and the possible differential regulation of the various
      nephron segments, desensitization to vasopressin (AVP) was studied on freshly
      isolated rat medullary thick ascending limbs (MTALs) and outer medullary
      collecting ducts (MCDs). Desensitization was induced through intramuscular
      injections of 1-deamino-8-D-arginine-vasopressin (dDAVP, 2 micrograms/day for 3
      days), the last of which was performed 1 h before kidney removal. The cellular
      response to AVP was studied by measuring cAMP accumulation in micro-dissected
      nephron segments. In the MTAL, we observed a marked (around 80%) and selective
      desensitization to AVP, the response to either glucagon or human calcitonin
      remaining unaltered. In the MCD, significant desensitization was observed in the
      presence of 1 nM AVP in the assay medium, and was no longer significant when the
      AVP concentration was increased to supramaximal levels (10-1,000 nM). These
      experiments thus reveal a clear dissociation between MTAL and MCD with regards to
      dDAVP-induced desensitization and extend previous observations made on target
      segments in the renal cortex.

PMID- 1375763
TI  - Cisplatinum-induced lesion of proximal tubule acidification in the rat.
AB  - Rats were given a 4- to 6-mg/kg body weight intraperitoneal injection of the
      antitumor drug, Cisplatin, 5-7 days prior to experiments to study tubule
      acidification by clearance and stationary microperfusion techniques. Cisplatin
      reduced the glomerular filtration rate markedly and caused a moderate degree of
      metabolic acidosis, but urine acidification (pH) was well maintained. Proximal
      tubule stationary pH and bicarbonate concentrations, as measured by pH
      microelectrodes, were significantly increased. The defect of proximal H+
      secretion is reflected by increased acidification half-times (from 4.44 to 10.2
      s) and reduced bicarbonate reabsorption to 37% of control values. H-ion back
      flux, measured during tubule and capillary perfusions with Ringer's bicarbonate-
      and CO2-free phosphate solutions, was reduced to 68% of control values. The
      apparent H-ion permeability was lowered from 0.79 to 0.54 cm/s. These results
      indicate that proximal acidification is reduced by impairment of H+ transport and
      not by increased transepithelial H+ shunting. Blunted acidification is compatible
      with a reduction in the number of Na/H exchangers in the proximal brush border
      and/or a decrease in the apical sodium gradient, the driving force for proximal H
      ion secretion. Cortical distal tubule acidification, measured by double-barreled
      ion-exchange resin/PD microelectrodes, was not significantly affected by
      Cisplatin. This accounts for the observation that, in spite of the impaired
      proximal acidification, urine pH is kept within the normal range.

PMID- 1375765
TI  - Effect of prostaglandin synthesis inhibition on the tubuloglomerular feedback
      control in the rat kidney.
AB  - It is known that intact prostaglandin synthesis is of some importance for
      tubuloglomerular feedback (TGF). In this study the effects of cyclooxygenase
      inhibition by oral fenflumizole, an imidazole derivative, on TGF in rats after
      acute elevation of ureteral pressure were investigated by comparison with the TGF
      mechanism in untreated rats. The effects of fenflumizole on the TGF mechanism
      were also compared with those of indomethacin injection. To characterize the TGF
      mechanism proximal tubular stop-flow pressure (Psf) was measured during perfusion
      of the loop of Henle with an artificial perfusion solution with a composition
      resembling that of the proximal fluid. The perfusion rate was varied from 0 to 40
      nl.min-1, in steps of 2.5-5 nl.min-1, permitting measurement of the maximal
      pressure response delta Psf, to increased tubular perfusion, and the perfusion
      rate which elicited a half-maximal drop in Psf, designated the turning point
      (TP). Both cyclooxygenase inhibitors caused a significant increase in TP from a
      control value of 21 to approximately 27 nl.min-1. TP remained at this level in
      fenflumizole-treated rats, even after elevation of ureteral pressure, a situation
      in which TGF is normally not detectable. From these and earlier investigations we
      conclude that the prostaglandin system is of importance for a normally operating
      TGF control mechanism, both under normal conditions and, especially, in
      conditions in which resetting of TGF is observed.

PMID- 1375766
TI  - Atrial natriuretic factor infusion following acute renal ischemia in anesthetized
      dogs.
AB  - Atrial natriuretic factor (ANF) has been shown to be effective in reversing renal
      functional impairments following renal ischemia. We studied the effects of a
      nonhypotensive intravenous ANF infusion (100 ng/min x kgBW, 60 min) after 90 min
      unilateral renal arterial occlusion in anesthetized dogs with an intact
      contralateral kidney. ANF plasma levels remained unchanged in controls (group 1)
      and increased in ANF-infused animals (group 2) from 22 +/- 3 to 552 +/- 124
      pg/ml. Blood pressure increased in both groups during renal ischemia, but
      returned to control values in group 2 when ANF infusion was started. Plasma
      vasopressin did not change in group 1, but increased in group 2 (0.77 +/- 0.29
      vs. 1.10 +/- 0.49 pg/ml) after terminating ANF infusion. The postischemic fall in
      creatinine clearance (CCr), filtration fraction (FF) and renal blood flow (RBF)
      was prevented by infusion of ANF (CCr: group 1, 0.16 +/- 0.05 vs. group 2, 1.01
      +/- 0.25 ml/min x kgBW; FF: group 1, 4.0 +/- 1.6 vs group 2, 14.1 +/- 4.1%; RBF:
      group 1, 6.0 +/- 1.2 vs. group 2, 9.2 +/- 1.6 ml/min x kgBW); however, the
      effects were limited to the time of infusion and the postischemic increase in
      urinary excretion of the proximal tubular enzyme N-acetyl-beta-D-glucosaminidase
      (NAG; group 1, 317.7 +/- 163.6 vs. group 2, 672.4 +/- 245.7 microU/min x kgBW)
      was not improved by ANF. Our data suggest that infusion of ANF transiently
      reverses postischemic renal impairment. However, the failure to demonstrate a
      sustained postischemic improvement of renal functional parameters and to
      ameliorate massive NAG excretion casts doubt on the benefit of ANF infusion in
      preventing cellular damage.

PMID- 1375767
TI  - Long-term renal handling of sodium and calcium in spontaneously hypertensive
      rats.
AB  - The renal handling of sodium and calcium in spontaneously hypertensive rats (SHR)
      was investigated over an extended period (10-75 weeks of age) and compared with
      age-matched normotensive Wistar-Kyoto controls. The animals were fed a standard
      rat chow except during screening periods when liquid diet that matched the pellet
      chow was substituted. Sodium balance, urinary excretion of sodium and calcium,
      fractional excretion of sodium (FENa), and renal cortical dopamine receptors (DA1
      and DA2) were measured at 10, 30, 60 and 75 weeks of age. The results showed no
      difference between the two strains except for FENa, which was significantly
      higher in the SHR at 75 weeks coincident with decreased glomerular filtration
      rate. We conclude that a defect in renal handling of sodium and/or calcium is not
      a major factor in the maintenance of hypertension in the SHR.

PMID- 1375768
TI  - Permeability of the macula densa basement membrane area to high molecular weight
      molecules.
AB  - To investigate the permeability properties of the basement membrane beneath
      macula densa cells and between extraglomerular mesangial cells, thick ascending
      limbs with attached glomeruli were dissected from rabbit kidney and incubated in
      a Ringers solution containing either horseradish peroxidase (HRP) (1 mg/ml;
      molecular weight approximately 40,000) or native or cationic ferritin (both at 5
      mg/ml molecular weight approximately 450,000) for 5 and 20 min at room
      temperature. Tubules were processed for electron microscopy. At both time points,
      HRP reaction product fully permeated the matrix material between extraglomerular
      mesangial cells, the basement membrane underneath the macula densa, and also was
      occasionally located in intercellular spaces and intracellular vesicles within
      macula densa cells. Similar results were obtained with native and cationic
      ferritin. In separate experiments, thick ascending limbs with attached glomeruli
      were perfused for 20 min at room temperature with a Ringer solution containing
      HRP (1 mg/ml). HRP was found in tubulovesicular bodies within the apical
      cytoplasm of macula densa cells again indicating that these cells exhibit
      endocytotic activity. However, HRP did not gain access to intercellular spaces
      indicating that the apical junctional complex was impermeable to HRP. These
      results demonstrate that the macula densa basement membrane and matrix material
      between extraglomerular mesangial cells is permeable to high molecular weight
      molecules and suggest unhindered diffusion of water and solutes within this area.

PMID- 1375770
TI  - [Immunotherapy of recurrent spontaneous miscarriages (idiopathic abortive
      disease): preliminary results].
AB  - Recurrent spontaneous abortion (greater than or equal to 3 spontaneous
      miscarriages) represents an entity defined by negative criteria (absence of
      anatomical, hormonal, autoimmune and chromosomal abnormalities). The immune
      hypothesis is corroborated by the successes (greater than or equal to 80 %) of
      specific (paternal leucocytes) or non-specific (intravenous gammaglobulins)
      immunotherapeutic trials. Studies on the mechanisms of action of those two
      methods will afford information on the pathogenesis of this condition.

PMID- 1375771
TI  - [Role of the nurse caring for a patient who was operated for varicose veins under
      local anesthesia].

PMID- 1375769
TI  - Mechanism of acetazolamide-induced rise in renal vascular resistance assessed in
      the dog whole kidney.
AB  - The reduction in renal blood flow (RBF) and glomerular filtration rate (GFR)
      observed after the administration of the carbonic anhydrase inhibitors
      acetazolamide and benzolamide had been explained as due to activation of the
      tubuloglomerular feedback mechanism. If correct, pharmacologic blockade of this
      pathway should prevent the development of renal vasoconstriction with the
      carbonic anhydrase inhibitors. Thus, the current study evaluates in the dog whole
      kidney the effect of acetazolamide (20 mg/kg body weight) in the presence or
      absence of furosemide (5 mg/kg body weight), a drug which blocks the
      tubuloglomerular feedback. Acetazolamide resulted in a large increase in urinary
      bicarbonate excretion accompanied by a significant reduction in GFR (16%) and RBF
      (18%). By contrast with the effects of acetazolamide, furosemide did not alter
      GFR and increased RBF. In addition, the loop diuretic induced a large chloruresis
      without changes in urinary bicarbonate excretion. The infusion of acetazolamide
      in furosemide-treated dogs resulted in a significant increment in renal
      bicarbonate excretion and in a significant reduction in the levels of both GFR
      (28%) and RBF (13%). Therefore, furosemide pretreatment did not block the effects
      of acetazolamide on renal hemodynamic parameters. Consequently, the acetazolamide
      induced reduction in both GFR and RBF cannot be accounted for by changes in
      chloride levels in the juxtaglomerular region due to enhanced salt transport in
      the macula densa/distal nephron. The increased renal vascular resistance observed
      with acetazolamide might occur by either a direct effect of this agent on the
      renal circulation or as a result of changes in intrarenal pressure secondary to
      the inhibition of proximal fluid reabsorption.

PMID- 1375773
TI  - Doing an effective poster presentation.

PMID- 1375772
TI  - [Prostate carcinoma--a current review].
AB  - Carcinoma of the prostate is the most commonly diagnosed cancer in men. The
      natural history and the biological aggressiveness are primarily determined by
      tumor volume. At the time of diagnosis, only one third of all tumors are
      pathologically confined to the prostate and eligible for curative therapy. Early
      detection by the general practitioner with prostate-specific antigen and digital
      rectal examination should be the primary goal. Currently, diagnosis is best
      established by transrectal ultrasound-guided biopsies. For the treatment of
      localized prostate cancer, men who undergo radical retropubic prostatectomy have
      been shown to have superior long-term results when compared to those who have
      received radiation therapy. With an improved understanding of the prostatic
      anatomy and nerve-sparing surgical techniques, morbidity from impotence and
      incontinence are minimal. In advanced carcinoma, 70 to 80% of men initially
      respond well to androgen withdrawal. Unfortunately, androgen-independent cells
      will continue to multiply, leading to tumor progression and death. Until
      effective chemotherapeutic agents are developed, we can only achieve palliation
      in advanced disease.

PMID- 1375775
TI  - [In memory of Gunter Baumgartner (1 September 1924-11 August 1991)].

PMID- 1375774
TI  - Flow cytometric analysis of reticulocytes using an RNA-binding fluorochrome.
AB  - The reticulocyte count is an important parameter in the diagnosis of anaemia. The
      commonly used microscopic counting technique is, however, laborious and hampered
      by poor precision and low sensitivity. An alternative method has recently been
      developed, which is based on flow cytometric identification and quantification of
      reticulocytes after staining with an RNA-binding fluorochrome, thiazol orange.
      The two methods were compared both in a sample of healthy individuals and in
      patient specimens. The correlation between the methods was good, but the flow
      cytometric analysis consistently gave values approximately 1.5 times higher
      (reticulocytes in per cent of erythrocytes) than the microscopic technique. The
      coefficient of variation was significantly lower for the flow cytometric
      technique. Reference values for the reticulocyte count were determined and the
      effects of storage of specimens were evaluated. It is concluded that flow
      cytometric analysis of reticulocytes is more sensitive and has a better precision
      that the standard microscopic procedure.

PMID- 1375776
TI  - [Obsessive behavior and thoughts in patients with myasthenia gravis].
AB  - 230 patients with myasthenia gravis were investigated by a german questionnaire,
      the HAMBURGER-ZWANGS-INVENTAR, in order to quantify their obsessive and
      compulsive behaviour. Compared to normals, myasthenic patients show higher scores
      on the compulsion-subscales of the inventory. The most significant differences
      appeared on the orderliness-subscale. On the other hand ratings of obsessive
      behaviour are significantly lower than in the normal population. Especially
      (auto)aggressive ruminations do hardly occur in myasthenia, which is a remarkable
      fact in this autoaggressive immunological disease. Compulsive behaviour cannot be
      interpretated as clinical compulsive disorder, caused by myasthenia.
      Questionnaire replies rather indicate one aspect of the way of coping with the
      disease and its treatment.

PMID- 1375778
TI  - [Swiss Society for Clinical Neurophysiology. 12th annual meeting, Agno/Lugano, 2
      4 May 1991].

PMID- 1375777
TI  - [Etiology, follow-up and therapy of seizure clusters in temporal lobe epilepsy
      and catamenial epileptic seizures].
AB  - The phenomenon of seizure clustering is still poorly understood. We therefore
      investigated 192 patients with temporal lobe epilepsies among whom 60 showed
      clustering of seizures. The percentage of women was significantly higher in the
      cluster than in the non-cluster group, the history of epilepsy lasted longer and
      the excess of complex partial seizures over tonic clonic seizures was more
      prominent in the cluster group. In 46 out of the 60 patients the clustering did
      not occur initially but developed in the course of the disease. In a particular
      subgroup the development initiated with isolated tonic clonic seizures, in a
      later phase complex partial seizures appeared and finally only complex partial
      seizures remained. This type of history was found significantly more frequent in
      the cluster than in the non-cluster group (27% versus 7%). It is conjectured that
      endogenous, as well as exogenous factors, both of them not completely revealed,
      cause the occurrence of clusters; anticonvulsant drug therapy might even enlarge
      this trend. Patients with seizure clustering tend to be pharmacoresistant.
      Chronic therapy with antiepileptic drugs besides intermittent therapy with
      benzodiazepines may help. A particular type of seizure clustering is observed in
      catamenial epilepsies where seizures appear in the perimenstrual and/or
      periovulatory phase of the menstrual hormonal cycle of females. This type of
      seizure incidence is obviously influenced by hormonal rhythms. Ten patients
      suffering from catamenial epileptic seizures were therefore treated with a
      synthetic analogue of GnRH in order to suppress the menstrual hormonal rhythm. As
      a result 3 patients became seizure free and in 5 patients seizure frequency
      decreased.

PMID- 1375779
TI  - [Graduate education for psychiatry and psychotherapy specialty FMH: retrospective
      evaluation by the psychiatrist. 1].
AB  - Psychiatrists who recently finished their postgraduate training filled in a
      questionnaire about their training experiences. Two thirds considered the
      training as generally insufficient although many gave high ratings when asked
      about the quality of their clinical experiences and the acquisition of skills. It
      appears that the main areas for possible improvement of the training should
      concern knowledge and practical experiences with disorders which are typical for
      psychiatric out-patients.

PMID- 1375780
TI  - [Graduate education in psychiatry and psychotherapy specialty FMH: retrospective
      evaluation by psychiatrists. 2].
AB  - A questionnaire filled in by psychiatrists shortly after the end of their
      postgraduate training showed that the majority invested a considerable amount of
      time and money for a psychotherapy training on private initiative. Three quarters
      had a training analysis. About 70% felt that their private training efforts had
      been more important than the official psychotherapy training in the institutions.
      Psychiatrists working in institutions tended towards a more positive rating of
      the official postgraduate training.

PMID- 1375781
TI  - [Environmental dependence in brain lesions: imitative behavior, prehension and
      utilization].
AB  - This paper reviews the literature on clinical signs such as imitation behavior,
      grasp reaction, manipulation of tools, utilization behavior, environmental
      dependency, hyperlexia, hypergraphia and echolalia. Some aspects of this
      semiology are of special interest because they refer to essential notions such as
      free-will and autonomy.

PMID- 1375782
TI  - [Comparison of urography and ultrasonography findings in patients prior to
      prostatectomy].
AB  - In order to evaluate the assess of ultrasonographic examinations in patients
      before prostatectomy the authors correlated preoperative findings obtained by
      urography with ultrasonographic findings. Urography of the upper urinary pathways
      revealed 12 (18.8%) pathological findings, ultrasonographic examination 26
      findings (40.6%) in a group of 64 patients. While in 14 patients a pathological
      finding on ultrasonography was not revealed by urography, only in one patient
      with a positive urographic finding ultrasonography was negative. Ultrasonographic
      examination proved to be more valuable in assessing the post-miction residue, as
      compared with urography. Moreover, ultrasonography is useful for assessing the
      volume of tissue of benign prostatic hyperplasia. Correlation of the calculated
      volume of prostatic tissue by means of ultrasonography with the weight of removed
      tissue revealed a close linear correlation. Ultrasonographic examination of
      patients before prostatectomy replaced urography which proved to be unnecessary
      diagnostic procedure.

PMID- 1375783
TI  - [Neuropeptides in pathogenesis of arthritis].

PMID- 1375784
TI  - Unusual prevalence of the rare serovar Da of Chlamydia trachomatis in Greece
      detected by monoclonal antibodies.
AB  - Twenty-seven monoclonal antibodies (mAb), eight with subclass-specificities and
      nineteen reacting with one or two C. trachomatis serovars, were developed and
      used to immunotype twenty-six clinical isolates from Greek patients with
      chlamydial infections. Twelve samples, first classified as serovar D, were
      identified as the recently established serovar Da on the basis of their negative
      reaction with mAb JG9, an mAb previously shown to distinguish between D and Da,
      and a new mAb 114D9 with similar specificity. The 12 Da strains represent the
      highest prevalence of the rare serovar Da that has been reported worldwide.
      Further characterization of mAbs JG9 and 114D9 revealed a unique cross-reactivity
      of the D-specific JG9 with the mouse biovar MoPn. Epitope mapping studies on
      overlapping synthetic peptides of the fourth variable domain of the MOMP of
      serovar D and Da localized the epitopes of JG9 and 114D9 and a D/Da specific mAb
      113D5 within this domain. The results were consistent with the specificity of
      these mAbs observed with whole microorganisms and indicated their usefulness as
      epidemiologic markers.

PMID- 1375785
TI  - Transhiatal bilateral splanchnicotomy for pain control in pancreatic cancer:
      basic anatomy, surgical technique, and immediate results in fifty-one cases.
AB  - The greater splanchnic nerves are largely responsible for innervation of the
      supramesenteric viscera; their section is known to be efficient to relieve
      pancreatic pain. Transhiatal splanchnicotomy (THS) is easily performed through a
      midline laparotomy. The nerve trunks are readily identified in the submediastinal
      space, far from the pancreatic cancer motivating splanchnicotomy, and can be
      sectioned safely and completely. After carrying out an anatomic study to
      determine the level of origin and mode of constitution of the greater splanchnic
      nerve trunk and its relations to the posterior and lower mediastinum, 51 patients
      underwent THS for intractable pain caused by unresectable pancreatic
      adenocarcinoma. THS alone was performed in 22 cases. THS was performed in
      association with biliary tract diversion or gastroenteroanastomosis in the other
      cases. All tumors were considered unresectable during surgery, and no patient was
      operated on with the sole purpose of performing THS. Two deaths (3.9%) were
      unrelated to THS. Specific morbidity was 6% (one pneumothorax, one chylothorax,
      and one splenic injury). Immediate postoperative functional results were good in
      86.3% of patients treated by THS alone (group 1) and in 80.7% of patients treated
      by THS and bypass (group II). Functional results decreased to 72.7% in group I
      and 62.1% in group II, 3 months after surgery. In conclusion, THS appears to be
      an efficient technique for relief of pancreatic neoplastic pain and need not be
      combined or confused with medical percutaneous methods of neurolysis.

PMID- 1375786
TI  - Repair of posterolateral ventral herniation caused by diabetic truncal
      neuropathy.
AB  - Abdominal pain caused by diabetic radiculopathy is uncommon, and abdominal hernia
      as a complication is rare. We report a case of abdominal wall herniation caused
      by diabetic truncal radiculopathy requiring surgical repair. Clinical and
      diagnostic features of this entity are reviewed.

PMID- 1375787
TI  - Biological properties of a crude venom extract from the greater weever fish
      Trachinus draco.
AB  - Crude venom of the greater weever fish, Trachinus draco was analyzed to assess
      its toxicity, stability and biological properties. The best yield of venom was
      obtained by extraction in physiological saline of the whole venom apparatus of
      the fish which were shock-frozen and stored at -70 degrees C. This extract had a
      mouse i.v. minimum lethal dose of 1.8 micrograms protein per gram mouse and a
      total of 61,000 minimum lethal doses were obtained from venom apparatus of one
      fish. The lethal activity was unstable at room temperature especially at lower
      protein concentrations. Stability was achieved either by storing the extract at 
      70 degrees C or by precipitation with ammonium sulfate at 50% saturation.
      Toxicity of the crude venom was abolished by trypsin treatment. The crude venom
      did not possess any proteolytic or histamine-releasing activities. The venom
      caused an outflow of tetraphenylphosphonium from preloaded rat brain particles in
      a concentration-dependent manner. Like toxicity, this effect was also abolished
      by trypsin treatment or by keeping the venom at higher temperatures. The crude
      venom also possessed hemolytic activity with an EC50 for rabbit erythrocytes of
      75 ng/ml venom protein. The hemolytic activity was also sensitive to heat and
      proteolytic treatment. Rabbit erythrocytes were most sensitive to venom followed
      by rat erythrocytes. Mouse and cattle erythrocytes were only slightly sensitive,
      whereas human, chicken and guinea pig erythrocytes were totally resistant.

PMID- 1375789
TI  - Temporal relation of calcium-calmodulin binding and neuronal damage after global
      ischemia in rats.
AB  - BACKGROUND AND PURPOSE: This study explores the temporal relation of the severity
      of ischemia and calcium-calmodulin binding in vulnerable and resistant brain
      regions in a commonly used model of global ischemia. METHODS: Immunohistochemical
      assay of free calmodulin unbound to calcium and light microscopic histological
      damage were measured in rats after 5, 10, or 20 minutes of global ischemia.
      RESULTS: After 24 hours of reperfusion, decreased calmodulin staining,
      representing increased calcium influx and calcium-calmodulin binding, correlated
      with increasing durations of ischemia across all brain regions. Based on a 4
      point scale (4, extensive stain; 0, no staining), calmodulin staining after 5
      minutes versus 10 minutes of ischemia was 3.2 versus 1.9, respectively (p less
      than 0.05) and after 10 minutes versus 20 minutes of ischemia was 1.9 versus 1.0,
      respectively (p less than 0.01). The CA1 region displayed the greatest
      sensitivity to ischemia. Similar but less dramatic results were seen after 2
      hours of reperfusion. After 72 hours of reperfusion, histological damage closely
      correlated with calcium-calmodulin binding after variable durations of ischemia.
      A threshold of 10 minutes of ischemia was required to cause calcium-calmodulin
      binding and irreversible neuronal damage. Surviving neuronal populations showed
      recovery of calmodulin staining 7 days after ischemia, representing a return of
      free calmodulin and normal calcium homeostasis. CONCLUSIONS: These correlations
      between calcium-calmodulin binding, histological damage, and duration of ischemia
      support the causal role of calcium influx in global ischemic injury and suggest
      the need for very rapid intervention after ischemia if calcium-mediated damage is
      to be prevented.

PMID- 1375788
TI  - Intrinsic lethality of chloride-channel-directed insecticides and convulsants in
      mammals.
AB  - The intrinsic lethality of a series of chloride-channel-directed convulsants and
      insecticides was determined by intracerebral injection into mice. The toxicities
      of the cyclodiene insecticides and picrotoxinin were potentiated by intracerebral
      injection, when compared to their reported intraperitoneal LD50s. In contrast,
      the toxicities of lindane, abamectin, and the bicyclic convulsants TBPS and a
      TBOB analog were approximately the same by either route of administration. These
      results suggest that the brain is the primary target site for the cyclodienes and
      picrotoxinin, while the peripheral nervous system may be relatively more
      important in the toxic action of lindane, abamectin, and bicyclic convulsants
      such as TBPS. With the exception of picrotoxinin these compounds showed, overall,
      a good correlation between acute intracerebral toxicity and potency for
      inhibiting GABA-dependent chloride uptake. The evidence that multiple chloride
      channel subtypes serve as targets for these compounds and the potential impact
      this had on the results of these studies are discussed.

PMID- 1375790
TI  - Fresco-Alberts-Doty model.

PMID- 1375791
TI  - The varieties of ribonuclease P.
AB  - Ribonuclease P is a ribozyme involved in tRNA processing that is present in all
      cells and organelles that synthesize tRNA. Most of our understanding of
      ribonuclease P derives from studies of the bacterial enzyme. This enzyme has been
      characterized biochemically and a secondary structure for the RNA subunit has
      been proposed. Isolation and characterization of ribonuclease P from diverse
      Archaea and Eukarya are now modifying and adding to our model of this unusual
      enzyme. The latter instances of RNase P differ from the bacterial version, but
      similarities are emerging.

PMID- 1375792
TI  - Antigenic relationships of foot-and-mouth disease virus serotype Asia-1 isolates
      demonstrated by monoclonal antibodies.
AB  - A panel (26) of monoclonal antibodies (MAbs) was elicited against three distinct
      isolates of foot-and-mouth disease virus (FMDV) serotype Asia-1. Each MAb was
      characterized according to the location of its epitope: Class I, restricted to
      the intact virion (140S); Class II, restricted to 140S and the virion protein
      subunit (12Sps); Class III, available on 140S, 12Sps and virus protein 1; Class
      IV, restricted to 12Sps. In addition, the MAbs were further categorized by
      isotype, neutralization of viral infectivity, capacity to bind in
      radioimmunoassay and precipitation in the Ouchterlony reaction. Neutralization of
      FMDV infectivity by a MAb of the IgA isotype is reported for the first time. A
      minimum of seven distinct neutralization epitopes were described on FMDV Asia-1.
      Some of the neutralizing MAbs bound FMDVs in addition to those that they
      neutralized. The MAbs defined epitopes common to FMDV serotypes Asia-1, A, O1 and
      C but neutralizing capacity was restricted to serotype Asia-1. Class IV MAbs
      defined epitopes highly conserved throughout the FMDV serotypes. Identification
      of FMDV neutralization epitopes makes possible the direct selection of optimal
      FMDV strains for vaccine fabrication. In addition, these data are crucial to the
      design of future synthetic vaccines.

PMID- 1375793
TI  - Proliferating cell nuclear antigen in malignant and pre-malignant lesions of
      epithelial origin in the oral cavity and the skin: an immunohistochemical study.
AB  - Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the
      late G1 and S phase of the cell cycle and immunohistochemical detection of the
      protein represents a useful marker for the proliferating fraction of cells in
      tissue specimens. A series of malignant and pre-malignant lesions of the oral
      cavity and skin were evaluated by the streptavidin biotin immunoperoxidase method
      for detection of this protein. Monoclonal anti-PCNA antibody (PC 10) labelled
      proliferating cells in all cases with varying intensity of nuclear staining. In
      squamous cell carcinoma (n = 48), PCNA positivity correlated with the
      differentiation and atypia of the tumour cells; however, in poorly differentiated
      tumours, the relationship between PCNA expression and proliferation was lost.
      Basal cell carcinoma showed an increased growth fraction in tiny epithelial nests
      (mean 43.8, SD 6.0, n = 20) than in neoplastic basal cells (mean 30.1, SD 6.9, n
      = 8). The growth fractions were significantly higher in the pre-malignant lesions
      (leukoplakia, mean 22.3, SD 7.7, n = 14; Bowen's disease, mean 45.2, SD 11.7, n =
      12; senile keratosis, mean 41.2, SD 7.0, n = 12) than in the normal mucosa (mean
      9.8, SD 4.9, n = 10), suggesting that cellular growth fractions correlate with
      the degree of dysplasia in pre-malignant lesions.

PMID- 1375794
TI  - Expression of c-erbB-2 protein and epidermal growth factor receptor in normal
      tissues of the female genital tract and in the placenta.
AB  - The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor
      receptor that has molecular homology with the epidermal growth factor receptor
      (EGFR). To investigate the relationship between the expression of c-erbB-2
      protein and EGFR in the tissues of the human female genital tract and in the
      placenta, we examined the immunohistochemical reactivity of monoclonal antibodies
      against both of these proteins. In the mullerian-derived genital tract,
      epithelial cells of the fallopian tube, endometrium, and endocervix showed
      reactivity for c-erbB-2 protein, whereas reactivity for EGFR was distributed
      mainly in the stromal cells throughout the menstrual cycle and during pregnancy.
      In addition, the staining intensity for EGFR in the endometrial stroma increased
      with its decidualization. In the exocervical squamous epithelium, basal cells
      were c-erbB-2 protein-negative and EGFR-positive, but the more differentiated
      squamous cells of the intermediate layer were c-erbB-2 protein-positive and EGFR
      negative. In the placental tissues, cytotrophoblasts and syncytiotrophoblasts of
      the chorionic villi were c-erbB-2 protein-negative and EGFR-positive. In
      contrast, intermediate trophoblasts in the extravillous space were c-erbB-2
      protein-positive and EGFR-negative. Thus, there is an inverse relationship
      between the expression of c-erbB-2 protein and EGFR in the tissues of the female
      genital tract and in the placenta. This suggests that there may be a regulatory
      mechanism(s) for the expression of both proteins that is associated with the
      differentiation and/or function of cells in the female genital tract and the
      placenta.

PMID- 1375795
TI  - Light and electron microscopic immunolocalization of endothelial leucocyte
      adhesion molecule-1 in inflammatory bowel disease. Morphological evidence of
      active synthesis and secretion into vascular lumen.
AB  - Endothelial leucocyte adhesion molecule-1 (ELAM-1) is a rapidly inducible
      adhesion molecule for neutrophils in vascular endothelial cells. We investigated
      its immunohistochemical localization in 17 cases of inflammatory bowel disease.
      ELAM-1 was preferentially expressed in venules in actively inflamed mucosa and
      granulation tissue. Most capillaries were negative for ELAM-1. In areas with mild
      inflammation its expression diminished markedly and in normal mucosa of the colon
      and small intestine its expression was sparse. Electron microscopically, venules
      in active inflammation had swollen endothelial cells with well-developed rough
      endoplasmic reticulum. Immunoelectron microscopy revealed ELAM-1 localization
      along the luminal plasma membrane and in rough endoplasmic reticulum and round
      granules, findings suggestive of active production in endothelial cells.
      Furthermore, exocytosis of immunoreactive substance into the lumen was confirmed.
      Our study suggests that venules in actively inflamed area play an important role
      in eliciting and/or maintaining acute inflammatory processes by active permeation
      of neutrophils from the blood stream into the tissue, and that ELAM-1 may be a
      secretory protein as well as a transmembrane receptor protein.

PMID- 1375796
TI  - The distribution and possible function of gamma interferon-immunoreactive cells
      in normal endometrium and myometrium.
AB  - T-lymphocytes are present in normal endometrium, where they may have a role in
      the control of glandular maturation. T-cell activity could be related to the
      local secretion of cytokines such as gamma interferon, which has an anti
      proliferative effect on endometrial epithelial cells in vitro. We have examined
      gamma interferon immunoreactivity and T-cell distribution in 24 normal pre
      menopausal uteri. Endometrial appearances were representative of all stages of
      the menstrual cycle. Most cells in the lymphoid aggregates in the stratum basalis
      were stained by T-cell and gamma interferon antisera. T-lymphocytes were also
      scattered in glandular epithelium and throughout the stroma of basal and
      functional layers; immunoreactivity for gamma interferon was less consistent in
      these cells. There was no alteration in the intensity or distribution of gamma
      interferon staining in different phases of the menstrual cycle. Endometrial
      granulocytes (K-cells) present mainly in the late secretory endometria were not
      reactive with the gamma interferon antiserum. In addition to endometrial
      staining, T-cells were distributed in all areas of the myometrium in most uteri,
      and many myometrial lymphocytes were gamma interferon positive. These results
      support a role for gamma interferon in endometrial physiology, possibly as an
      inhibitor of epithelial proliferation.

PMID- 1375797
TI  - Basement membrane proteins in salivary gland tumours. Distribution of type IV
      collagen and laminin.
AB  - Immunohistochemical localization of type IV collagen and laminin in normal
      salivary glands and in salivary gland tumours of various types was studied using
      rabbit antisera. In normal salivary glands, type IV collagen and laminin were co
      localized in basement membranes surrounding acini, ducts, fat cells and
      peripheral nerves. In salivary gland tumours, three main patterns of co
      expression of these basement membrane proteins were distinguished. Linear
      basement membrane-like staining was detected in duct-cell-derived benign salivary
      gland tumours and in acinic cell carcinomas. In invasive lesions, however, these
      basement membrane proteins were distributed in an irregular, interrupted manner,
      and in many cases they were completely absent. Both benign and malignant salivary
      gland tumours which have a prominent myoepithelial cell component display a
      particular deposition of basement membrane molecules adjacent to the modified
      myoepithelial cells, and at the margins of extracellular matrix deposits within
      these tumours.

PMID- 1375799
TI  - [Acute pancreatitis--a "Free radical disease". Decreasing mortality by sodium
      selenite (Na2SeO3) therapy].

PMID- 1375798
TI  - Nucleolar organizer regions of megakaryocytes in chronic myeloproliferative
      disorders.
AB  - To study megakaryocyte activation, the argyrophilic staining method of nucleolar
      organizer regions (AgNOR) has been applied to decalcified bone marrow biopsies of
      16 individuals with no haematopoietic disorders and 59 patients with chronic
      myeloproliferative disease. Of the 59 patients, 18 had chronic myeloid leukaemia
      (CML), 21 chronic megakaryocytic granulocytic myelosis (CMGM), 13 polycythaemia
      vera (PV) and 7 essential thrombocythaemia (ET). The AgNOR number of
      megakaryocytes in CML was significantly lower, and in CMGM, PV and ET
      significantly higher than in healthy individuals. The high number and the
      clusters of fine-grained AgNORs of megakaryocytes in CMGM, PV and ET are
      suggestive of active, proliferating cells. The AgNOR number of megakaryocytes and
      the platelet counts of the patients did not show a convincing correlation. In
      CMGM, PV and ET the pyknotic, heterochromatinized megakaryocytes with narrow rims
      of cytoplasm called bare (nude) nuclei, possessed few, large AgNOR granules. The
      AgNOR staining of bare nuclei and the roughly identical number of granules found
      in CMGM, PV and ET indicate a common, active mechanism of apoptosis.

PMID- 1375800
TI  - Progesterone and promegestone stimulate human bone cell proliferation and insulin
      like growth factor-2 production.
AB  - Recent clinical studies suggest that progesterone may be involved in the
      regulation of bone turnover and could promote bone formation. This study was
      undertaken to evaluate whether progesterone and promegestone (a 19 nor-PG
      derivative) may have a direct effect on human bone cells and, if so, whether
      growth factor production could be involved in promoting this effect. The
      osteosarcoma cell line TE85 and untransformed normal human osteoblastic cells
      derived from iliac crest were used as in vitro model systems. Progesterone and
      promegestone were found to significantly increase [3H]thymidine incorporation in
      TE85 cells in a dose-dependent manner at concentrations ranging from 10(-12) to
      10(-8) mol/l after four days of cultivation (p less than 0.01, ANOVA). Consistent
      with this response in the TE85 cells, progesterone and promegestone increased
      cell number in human osteoblastic cells after six days of treatment (p less than
      0.05, ANOVA). To determine whether this effect on cell proliferation was mediated
      by the insulin-like growth factor (IGF) regulatory system, the levels of IGF-1,
      IGF-2 and IGF binding protein (IGFBP) were measured in the conditioned media of
      both TE85 and human osteoblast cells. While no significant changes in IGF-1
      levels were found in the conditioned media of progesterone and promegestone
      treated cultures, progesterone and promegestone at the concentration of 5 nmol/l
      significantly increased IGF-2 levels 2.4 and 1.5-fold respectively, at 48 h in
      the conditioned medium of TE85 cells as compared to control. Similarly, a 4.1 and
      1.9-fold increase in IGF-2 levels was found upon treatment with progesterone and
      promegestone in human osteoblastic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375801
TI  - Risperidone versus haloperidol in the treatment of chronic schizophrenic
      inpatients: a multicentre double-blind comparative study.
AB  - Forty-four chronic schizophrenic inpatients participated in this multicentre 12
      week parallel-group double-blind trial. After a run-in period of 2 weeks and a
      single-blind placebo wash-out of 1 week, they were randomly assigned to treatment
      with either the serotonin2 and dopamine-D2 antagonist risperidone or haloperidol.
      Two patients were excluded from the efficacy analysis. Five patients dropped out
      in the haloperidol group and 1 in the risperidone group. At the end of the trial,
      the mean daily dose was 12 mg for risperidone and 10 mg for haloperidol. The
      risperidone group showed greater improvement on the Positive and Negative
      Syndrome Scale for Schizophrenia, the Schedule for Affective Disorders and
      Schizophrenia-change version, and the Nurses' Observation Scale for Inpatient
      Evaluation. The improvement of negative symptoms was more pronounced in the
      risperidone group until week 8 of double-blind treatment. The consumption of
      antiparkinsonian medication was 10 times lower with risperidone. Both drugs were
      well tolerated and the laboratory, endocrinological and cardiovascular safety
      parameters were comparable. This study suggests that risperidone is comparable to
      haloperidol as an antipsychotic, but that it has a safer EPS profile.

PMID- 1375802
TI  - Ventricular enlargement, clinical correlates and treatment outcome in chronic
      schizophrenic inpatients.
AB  - The ventricle-brain ratio (VBR) of 42 chronic schizophrenic patients was compared
      with that of 42 age-matched medical controls. For the schizophrenics, the
      relationship of various clinical parameters to the VBR was assessed, and the
      outcome of 12 weeks of double-blind treatment with either risperidone or
      haloperidol. The results confirm that schizophrenic patients have slightly
      enlarged lateral ventricles compared with medical controls. Only for
      schizophrenics, an effect of age, but not of duration of illness, was noticed.
      This study does not support the validity of a clinical subdivision of chronic
      schizophrenic patients on the basis of the VBR. Neither negative, positive nor
      general psychopathological symptoms, as measured by the Positive and Negative
      Syndrome Scale for Schizophrenia (PANSS), were related to the VBR, nor were
      abnormal involuntary movements or extrapyramidal symptoms. No association between
      season of birth or a family history of major mental disorder and VBR could be
      demonstrated. Treatment response was predicted by the total PANSS score and the
      PANSS general psychopathology subscale score at baseline. There was a trend for
      patients with higher VBR to have a more or haloperidol). or haloperidol).

PMID- 1375803
TI  - Nonlissencephalic cortical dysplasias: correlation of imaging findings with
      clinical deficits.
AB  - PURPOSE: To establish correlations between MR patterns and clinical outcome in
      patients with nonlissencephalic cortical dysplasias. PATIENTS AND METHODS: MR and
      clinical data from 36 patients with cerebral cortical gyral anomalies (other than
      classical type I or type II lissencephaly) were retrospectively reviewed. RESULT:
      The five patients with diffuse cortical dysplasia, including two with congenital
      infections, had microcephaly and severe development delay from a very early age.
      Infantile spasms occurred in three of the five. Focal areas of cortical dysplasia
      were most common in the frontal lobes, but were seen in all areas of the brain.
      The most common MR appearances were 1) a thickened, irregularly bumpy cortex with
      shallow, wide sulci, and 2) a deep infolding of thickened cortex. The twelve
      patients with bilateral focal dysplasia had a high incidence of bilateral motor
      dysfunction (67%), delayed speech (67%), and generalized developmental delay
      (92%). When the dysplasia was unilateral, contralateral spastic hemiplegia or
      monoplegia was present in 14 of 19 patients (74%), but dysphasia was uncommon,
      even in patients with dysplasia in the frontal lobe of the dominant hemisphere.
      CONCLUSION: Surgical resection of focal areas of cortical dysplasia in patients
      with medically refractory seizures is becoming more common, and the
      neuroradiologist will play an increasingly important role in the initial
      diagnosis and delineation of these anomalies.

PMID- 1375805
TI  - Assessment of different methods to detect increased autochthonous production of
      immunoglobulin G and oligoclonal immunoglobulins in multiple sclerosis.
AB  - The formulae for immunoglobulin G (IgG) synthesis rate, IgG(loc), IgG index, and
      IgG extended index in determining increased autochthonous production (intra-blood
      brain barrier synthesis) of IgG was assessed in 50 chronic progressive multiple
      sclerosis patients. The results of all four formulae clearly show elevated intra
      blood-brain barrier IgG synthesis in 35 patients, 94% of whom had oligoclonal
      immunoglobulins detected by the method of isoelectric focusing with
      immunofixation and silver staining (IEF-IS). The results from the four formulae
      are all normal in seven patients (none have oligoclonal immunoglobulins by IEF
      IS) and are discordant in eight patients (five have oligoclonal immunoglobulins
      by IEF-IS). Whenever intra-blood-brain barrier synthesis of IgG is suspected, IEF
      IS should be used to assay for oligoclonal immunoglobulins because this method is
      more sensitive than agarose electrophoresis with either Coomassie blue dye or
      silver stain (94% vs. 74% vs. 54%).

PMID- 1375804
TI  - Relationship between histopathologic typing and morphonuclear assessments of 238
      thyroid lesions. Digital cell image analysis performed on Feulgen-stained nuclei
      from formalin-fixed, paraffin-embedded materials.
AB  - A digital cell image processor was used to compute 15 parameters on Feulgen
      stained thyroid nuclei from 238 archival, i.e., formalin-fixed, paraffin-embedded
      thyroid lesions. The morphonuclear parameters were related to morphometric
      (nuclear area), densitometric (nuclear DNA content), and textural (chromatin
      pattern characteristics) features. With respect to development of a malignant
      condition, their variations were compared with the World Health Organization's
      International Histological Classification of thyroid tumors. The relationship
      between morphonuclear parameter assessments and tumor size and the presence or
      absence of metastasis at the time of diagnosis was also investigated: no
      relationship with respect to cytomorphonuclear assessments was found. Nuclear
      area and nuclear DNA content discriminated between simple multinodular goiters
      and multinodular goiters with adenomatous hyperplasia. In the same way, the mean
      parameter values describing the chromatin pattern of multinodular goiters were
      significantly distinct from those describing the chromatin pattern of adenomas
      and carcinomas. Furthermore, chromatin pattern descriptions made it possible to
      discriminate between cell nuclei from papillary carcinomas and follicular
      carcinomas, and further between follicular carcinomas and follicular adenomas. A
      marked variation was observed within individual cases of multinodular goiters,
      adenomas, and carcinomas, a feature suggesting that morphonuclear assessment is
      of limited value for the diagnosis of individual clinical cases. In contrast,
      these results show that morphometric, densitometric, and textural nuclear
      assessments are useful aids for thyroid tumor typing, adding interesting results
      with respect to thyroid tumor progression. Indeed, the primary findings
      demonstrate that nodules with adenomatous hyperplasia from multinodular goiter
      lesions and microvesicular adenomas more closely resemble follicular carcinomas
      than do simple multinodular goiters and normomacrovesicular adenomas. Such data
      might reflect a biologic progression from benign to malignant follicular thyroid
      lesions.

PMID- 1375806
TI  - Sexual abuse of children. The detection of semen on skin.
AB  - OBJECTIVE: The detection of semen on the skin of children who present within 72
      hours of an episode of sexual assault is critical to medical, forensic, and legal
      personnel. The Wood's Lamp, a UV light that causes semen to fluoresce, and four
      forensic laboratory techniques were compared to determine their sensitivity and
      decline in sensitivity over time. DESIGN: A descriptive study. PARTICIPANTS:
      Eleven adult female volunteers. MEASUREMENTS/MAIN RESULTS: Semen was placed on
      the skin of the volunteers. Samples of the dried semen were assessed during a 28
      hour period with the Wood's Lamp, microscopy, the acid phosphatase assay, and two
      assays for the prostatic protein p30 (counterimmunoelectrophoresis and enzyme
      linked immunosorbent assay). The intensity of the Wood's Lamp fluorescence of
      semen diminished dramatically by 28 hours; in contrast, the fluorescence of urine
      persisted up to 80 hours. Over time, the p30-enzyme-linked immunosorbent assay
      technique was more sensitive than microscopy, the acid phosphatase assay, and p30
      counterimmunoelectrophoresis in detecting semen on skin. CONCLUSIONS: The Wood's
      Lamp is not a sensitive screening tool and should be used with caution. To
      improve the detection of sexual abuse in children, we recommend that the p30
      enzyme-linked immunosorbent assay be used because of its potential as a more
      sensitive assay than those in current clinical use.

PMID- 1375808
TI  - Risk factors for surgery for prostatic hypertrophy.
AB  - The purpose of this case-control study was to evaluate potential risk factors for
      prostatic hypertrophy. The cases were 910 residents of Rhode Island who had a
      partial or total prostatectomy that was not related to cancer in the years 1985
      1987. The controls were 2,003 members of the source population who were selected
      from a list of holders of Rhode Island driver's licenses or a roster of older
      Americans compiled by the Health Care Financing Administration. Cases and
      controls were interviewed by telephone. The risk of prostatic hypertrophy was
      elevated in Jewish men compared with Protestants and Catholics and in blacks
      compared with whites. Risk was reduced in ever-married compared with never
      married men, in men who had left school at age 16 years or more compared with
      those who had left earlier, and in relatively tall or relatively heavy men.
      Coffee drinking and cigarette smoking were inversely but only weakly related to
      prostatic hypertrophy. There was a relatively strong, although irregular, inverse
      relation of beer drinking to prostatic hypertrophy. The associations of spirits
      and wine consumption with prostatic hypertrophy were weak.

PMID- 1375807
TI  - Home visitation for pregnant women and parents of young children.
AB  - Many of the most pervasive, intractable, and costly problems faced by high-risk
      women and young children in our society today are a consequence of adverse
      maternal health-related behaviors (such as cigarette smoking, drinking, and drug
      use during pregnancy), dysfunctional infant care giving, and stressful
      environmental conditions that interfere with individual and family functioning.
      These problems include low birth weight, child abuse and neglect, childhood
      injuries, unintended and closely spaced pregnancy, and reduced economic self
      sufficiency on the part of parents. Evidence is accumulating that these problems
      can be reduced with comprehensive programs of prenatal and infancy home
      visitation by nurses. While we are witnessing a renaissance of interest in home
      visitation as a means of addressing these problems, the recommendations of
      various health and human service advisory groups about the structure of proposed
      home-visitation initiatives are uncoordinated and frequently inconsistent with
      the empirical evidence. Home visitation is a promising strategy, but only when
      the program meets certain standards. The more successful programs contain the
      following: (1) a focus on families at greater need for the service, (2) the use
      of nurses who begin during pregnancy and follow the family at least through the
      second year of the child's life, (3) the promotion of positive health-related
      behaviors and qualities of infant care giving, and (4) provisions to reduce
      family stress by improving the social and physical environments in which families
      live.

PMID- 1375809
TI  - Alpha-fetoprotein levels in normal adults.
AB  - Alpha-fetoprotein (AFP) is a fetal specific glycoprotein normally produced
      primarily by the fetal liver. Normally, AFP levels decline rapidly after birth,
      reaching undetectable levels (less than 10 ng/ml) within several months after
      birth. The authors have developed a more sensitive radioimmunoassay, which has
      allowed them to study low levels of AFP in normal adults and to determine factors
      which may affect its normal level. Two hundred and seventy normal Houston blood
      donors were screened for the absence of hepatitis B and normal ALT levels. The
      mean AFP level was 3.04 ng/ml +/- 1.9 SD. There was a statistically significant
      higher level in men compared to women (p less than .004). Regression analysis
      demonstrated a statistically significant increase of AFP levels with age both in
      men (p less than .05) and in women (p less than .01). These data delineate the
      normal level of serum AFP in normal adults in the United States. With the normal
      level now defined, it becomes possible to compare levels in different populations
      including those exposed to hepatotoxins or hepatocarcinogens in the environment.

PMID- 1375810
TI  - The California Maternal Serum alpha-Fetoprotein Screening Program: the role of
      ultrasonography in the detection of spina bifida.
AB  - Between January 1988 and June 1990, 161 cases of open spina bifida were
      identified by the California Maternal Serum alpha-Fetoprotein Screening Program.
      Eight percent of these cases were not diagnosed by an initial ultrasonographic
      evaluation. Three defects were not recognized until birth. Ultrasonography is
      inadequate to identify all cases of open spina bifida.

PMID- 1375811
TI  - Maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and
      unconjugated estriol levels in midtrimester trisomy 18 pregnancies.
AB  - OBJECTIVE: The purpose was to evaluate the levels of maternal serum human
      chorionic gonadotropin, alpha-fetoprotein, and unconjugated estriol in trisomy 18
      pregnancies compared with normal singleton pregnancies. STUDY DESIGN: Sera from
      14 trisomy 18 pregnancies (13 retrospectively and one prospectively ascertained)
      were analyzed for human chorionic gonadotropin, alpha-fetoprotein, and
      unconjugated estriol. RESULTS: The alpha-fetoprotein levels in the 10 trisomy 18
      pregnancies without open neural tube or ventral wall defect had a median of 0.65
      multiple of the median, although two had alpha-fetoprotein levels above 2.5
      multiples of the median. The human chorionic gonadotropin levels had a median of
      0.32 multiple of the median and the unconjugated estriol levels had a median of
      0.56 multiple of the median. Although most women with trisomy 18 pregnancies had
      serum human chorionic gonadotropin levels that were less than 1.0 multiple of the
      median, three had markedly elevated human chorionic gonadotropin levels (greater
      than 5.0 multiples of the median). CONCLUSION: Our data are partially consistent
      with those previously published but suggest the possibility of a bimodal
      distribution of alpha-fetoprotein and human chorionic gonadotropin levels in
      trisomy 18-affected pregnancies, unrelated to a neural tube or abdominal wall
      defect. The efficiency of screening for trisomy 18 prospectively, using the three
      serum markers, requires further evaluation.

PMID- 1375813
TI  - Use of external memory aids with a head-injured patient.

PMID- 1375812
TI  - Chorionic villus sampling for fetal Rh typing: clinical implications.
AB  - OBJECTIVE: The prenatal Rh typing of red blood cells obtained by chorionic villus
      sampling was performed with an immune rosette technique. STUDY DESIGN: Ten Rh
      negative pregnant women undergoing chorionic villus sampling at 9 to 11 weeks'
      gestation were studied at a large referral hospital. RESULTS: Accurate Rh
      phenotyping may be done on red blood cells obtained from chorionic villi weighing
      2 to 8 mg. The preparations were shown to be greater than 90% fetal in origin as
      demonstrated by radial immunodiffusion quantitation of fetal hemoglobin
      containing cells. Of the 10 fetuses typed in the first trimester nine of the
      pregnancies were carried to term. In all cases typing of red blood cells
      confirmed the antenatal fetal red cell typing. CONCLUSIONS: This study shows that
      antenatal Rh phenotyping may be performed as early as 9 to 11 weeks' gestation.
      This technique may be used in the management of pregnancies complicated by Rh
      incompatibility.

PMID- 1375814
TI  - Surgery for disseminated abdominal sarcoma.
AB  - Seventy-two consecutive patients with disseminated soft tissue sarcoma in the
      abdomen were prospectively placed in a program of debulking surgery. The tumor
      was completely resectable in 64% of the patients. Following the first
      exploration, the median survival was 23 months for those with resection of
      metastases and 9 months for those without resection (p less than or equal to
      0.01); the former group had a survival rate of 28% at 3 years, 18% at 4 years,
      and 4% at 5 years (44%, 37%, and 10%, respectively, for low-grade sarcomas, i.e.,
      grade I or II sarcomas), whereas in the latter group, none survived for 3 years.
      In the group with resection, patients with grade III tumors had a median survival
      longer by 6 months, and those with low-grade tumors by 28 months (p less than or
      equal to 0.001), over the respective median survival of patients with
      unresectable tumors. Metastasectomy appeared to prolong survival in all patients
      and significantly so in patients with low-grade tumors and those with long
      disease-free intervals.

PMID- 1375815
TI  - Detection of proteins and phenol in DNA samples with second-derivative absorption
      spectroscopy.
AB  - We have employed near-uv second-derivative spectra of DNA, N-acetyl-L
      tryptophanamide, N-acetyl-L-tyrosinamide, N-acetyl-L-phenylalanine ethyl ester,
      and phenol in a matrix least-squares multicomponent analysis algorithm to detect
      the presence of tryptophan, tyrosine, phenylalanine, and/or phenol in DNA
      preparations. With this method, each of these compounds can be detected in a DNA
      sample (absorbance, 0.1) at absorbance levels of less than 0.002. In practice,
      the presence of proteins can be detected at absorbance levels of less than 0.003.
      Using second-derivative spectra of proteins, contents of mixtures of proteins and
      DNA can be determined with less than 1% error. Mixtures of DNA and RNA can also
      be quantitatively analyzed with an error of approximately 2%. This technique can
      be easily implemented with computer-controlled spectrophotometers equipped with
      standard spectral analysis software. With prerecorded standard spectra, the time
      of analysis does not exceed a few seconds.

PMID- 1375816
TI  - Will the calcium channel agonist BAY K8644 inhibit halothane-induced impairment
      of calcium current?
AB  - The inhaled anesthetics impair transsarcolemmal calcium entry (ICa) in myocardial
      cells, although the mechanism of this interaction is not known. This inhibition
      of calcium entry has been implicated in the myocardial depression of the volatile
      anesthetics. To further characterize this interaction and to evaluate whether a
      calcium channel agonist could attenuate or prevent the inhibition of calcium
      entry, the effect of the calcium channel agonist BAY K8644 on the impairment of
      ICa by halothane was evaluated in single guinea pig ventricular myocytes. Calcium
      currents were evoked by means of the whole-cell voltage-clamp technique. Baseline
      peak ICa was higher in the cells exposed to 5 microM BAY K8644 (311 vs 206
      pA/cm2, P less than 0.04). On exposure to 1% halothane, peak ICa was impaired to
      an identical degree whether or not cells were exposed to BAY K8644 (78% and 79%
      of baseline value). This is consistent with the suggestion that the effects of
      these agents on ICa are nonspecific. However, the increase in ICa suggests that
      appropriate calcium channel agonists might serve to ameliorate the myocardial
      depressant effects of halothane.

PMID- 1375817
TI  - Calcium channels are involved in the hypnotic-anesthetic action of
      dexmedetomidine in rats.
AB  - Our study examined whether calcium channels are involved in the anesthetic action
      of dexmedetomidine (100-300 micrograms/kg), a highly selective alpha 2
      adrenoceptor agonist. To investigate this, we studied the effects of verapamil
      (1.25 or 2.5 mg/kg), a calcium channel blocker, and BAY K8644 (0.5 or 1 mg/kg), a
      calcium channel agonist, on the hypnotic-anesthetic effect of dexmedetomidine in
      rats. Loss of the righting reflex was used to determine the presence of
      anesthesia, and its length in minutes was referred to as the duration of
      hypnosis. Verapamil significantly enhanced the duration of the hypnotic
      anesthetic action of dexmedetomidine (P less than 0.05). In contrast, BAY K8644
      caused a significantly increased onset of hypnosis (P less than 0.001) and
      attenuated the anesthetic property of dexmedetomidine. These results suggest that
      the hypnotic-anesthetic action of dexmedetomidine is influenced by the
      activation/gating of calcium channels.

PMID- 1375818
TI  - Patterns of expression of feline cytokeratins in healthy epithelia and mammary
      carcinoma cells.
AB  - Expression of keratins (cytokeratins, CK) in healthy feline epithelia and 2
      established feline mammary carcinoma cell lines was examined
      immunohistochemically and by use of immunoblotting analysis. A panel of specific
      anti-CK monoclonal antibodies (MAb) identifying epitopes unique to individual
      keratins or shared by 2 (or 3) CK polypeptides was used. Besides already
      available anti-human CK MAb, this panel of MAb consisted of 9 newly generated
      anti-human CK MAb and 1 newly generated anti-feline CK MAb. Immunohistochemical
      analysis on normal epithelia revealed that most of the anti-human CK MAb and the
      anti-feline CK MAb reacted with both feline and human epithelia, with a
      comparable tissue distribution pattern. However, slight differences in CK tissue
      distribution pattern between human beings and cats were detected by one MAb.
      Immunoblotting analysis revealed that all anti-human CK MAb that were
      immunohistochemically reactive with feline tissues detected analogous CK in cats,
      indicating the presence of a number of common epitopes on human and feline CK.
      Two continuous cell lines derived from 2 distinct feline mammary adenocarcinomas,
      K248C and K266, were analyzed with respect to their CK phenotype. Although no
      difference in CK expression between the 2 cell lines was detected in vitro, a
      difference in CK phenotype was detected on subcutaneous transplantation of the 2
      cell lines into nude mice. Although the K248C-induced adenocarcinomas maintained
      the same CK phenotype as observed in vitro, the CK pattern of the K266
      heterotransplants, growing as adenosquamous carcinomas, changed with squamous
      differentiation. Our findings confirm the high degree of homology between
      mammalian CK, and on the basis of those findings, we suggest that CK proteins
      provide a set of markers valuable for the characterization of normal and
      neoplastic feline tissues and for studies of squamous metaplasia.

PMID- 1375819
TI  - Airway eosinophils and lymphocytes in asthma. Birds of a feather?

PMID- 1375820
TI  - Effect of topical corticosteroids on the recovery of histamine releasing factors
      in nasal washings of patients with allergic rhinitis. A double-blind, randomized,
      placebo-controlled study.
AB  - Nasal washings (NW) have been used by many investigators as a readily available
      biologic fluid for studying the mechanism of allergic reactions. These fluids
      have been analyzed for the presence of various mediators, including cytokines.
      Recently, histamine releasing factors (HRF) have been detected in the NW. The
      objective of this study was to investigate the effect of treatment with topical
      corticosteroids on the recovery of these cytokines from the NW obtained from
      patients with allergic rhinitis. A group of 30 patients with ragweed pollen
      allergy were given either beclomethasone dipropionate (BDP) or placebo for 1 wk
      in a double-blind randomized manner. NW were performed twice before the start of
      the treatment period and were repeated twice at the end of the study. HRF
      activity was measured in the NW. Patients maintained a daily symptom score. The
      activity of HRF decreased significantly (mean +/- SD, pre = 37.2 +/- 21.3% versus
      post = 23.8 +/- 20.1%; p less than 0.01) in the BDP group, as did the mean
      symptom score (5.1 +/- 1.4 versus 1.5 +/- 1.5, p less than 0.01) at the end of
      the treatment period. In contrast, there was no significant change in HRF
      recovery (32.8 +/- 25.6% versus 33.8 +/- 25.3%; p less than 0.05) or symptom
      score (4.8 +/- 1.8 versus 5.4 +/- 1.9; p greater than 0.05) in the placebo group.
      There was a significant correlation between the net changes in symptom scores and
      the net differences in HRF activity. We speculate that the reduction in HRF in
      the nasal mucosa may contribute to the clinical efficacy of topical
      corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375821
TI  - Endoscopic laser therapy for obstructing and/or bleeding colorectal carcinoma.
AB  - The primary role of the neodymium yttrium aluminum garnet (Nd:YAG) laser has been
      to relieve obstruction and to control hemorrhage associated with malignant
      neoplasms throughout the gastrointestinal tract. In an initial series (IS), the
      authors demonstrated the efficacy of the Nd:YAG laser as initial preresectional
      therapy (PR) in 11 patients with obstructing and resectable left colonic or
      rectal tumors obviating initial operative diversion and allowing for primary
      resection and anastomosis. In addition, the authors have illustrated the benefit
      of the Nd:YAG laser in relieving obstruction and arresting bleeding in those
      patients with either widely metastatic or nonresectable (NR) locoregional
      disease. Their cumulative experience from 1985 to the present includes 53
      patients (PR: 29 and NR: 24). In the PR group, 25 lesions were above the
      peritoneal reflection and 4 below. Twenty-five patients underwent low anterior
      resection and four abdominoperineal resection. In the NR group, 17 patients were
      treated for imminent obstruction and 7 for bleeding. Ten lesions were above and
      14 below the peritoneal reflection. There was one laser-related complication in
      the series (1.8%). There was no significant morbidity or mortality in the PR
      group. The reduction in length of stay (LOS) and total hospital costs (THC), when
      compared to the IS has continued to be significant. Laser therapy for those
      patients in the NR groups is a safe and acceptable alternative to permanent
      colostomy with its accompanying morbidity and mortality.

PMID- 1375822
TI  - Cholinesterases in the amyloid angiopathy of Alzheimer's disease.
AB  - Vessels affected by amyloid angiopathy in patients with Alzheimer's disease also
      displayed intense acetylcholinesterase and butyrylcholinesterase activity when
      examined by light and electron microscopy. The enzymatic properties of the vessel
      bound cholinesterases were identical to those of the cholinesterases associated
      with senile plaques and neurofibrillary tangles. This cholinesterase activity is
      of unknown origin but represents one of the very few features common to all the
      major pathological markers of Alzheimer's disease.

PMID- 1375823
TI  - Push-through intubation: effective palliation in 409 patients with cancer of the
      esophagus and cardia.
AB  - Between 1980 and 1989, 355 patients with cancer of the esophagus and 54 with
      cancer of the cardia underwent push-through intubation because of advanced tumor
      stage or medical contraindications to tumor resection. In 36 other patients
      (8.1%), the attempt at transtumoral intubation failed. The hospital mortality
      rate after intubation was 3.4%. The following complications were observed:
      hemorrhage in 2.0% of the patients, esophageal perforation in 4.9%, tube
      dislodgment in 12.7%, and tube obstruction in 4.4%. Early resumption of semisolid
      oral feeding was possible in 80% of the discharged patients. The actuarial 1-year
      survival rate was 7.7% and the median survival, 3.9 months. In conclusion, push
      through intubation represents a valid therapeutic choice, which is indicated
      mainly for patients with a long, infiltrating, and circumferential stricture of
      the thoracic esophagus or cardia that is inoperable and for patients with an
      esophagorespiratory or esophagomediastinal fistula.

PMID- 1375824
TI  - Cryopreserved allograft repair of aortic hypoplasia and interrupted aortic arch.
AB  - Mortality for interruption of the aortic arch approaches 100% within the first
      year of life if untreated. Prostaglandin E1 can stabilize the patient's condition
      in anticipation of surgical palliation, but total repair is required for long
      term survival. Successful complete repair of type B interrupted aortic arch,
      hypoplasia of the left ventricular outflow tract, and ventricular septal defect
      was possible using a cryopreserved allograft in a child who previously had
      undergone unusual palliation.

PMID- 1375825
TI  - [New data on the leukocyte functional morphology in pyo-septic processes].
AB  - It is established by electron microscopical radioautography that sepsis results
      in the lowering of neutrophils bacterial capacity while their absorptive capacity
      is retained. Living bacteria may be released from neutrophils undergoing
      degradation into the environment. The same is observed when phagocytized but
      still living bacteria are located in phagosomes which are fused with one another
      and with neutrophil plasma membrane; after the destruction of the latter bacteria
      are released into the extracellular space. This is a negative issue for the host
      of the incomplete phagocytosis. Neutrophils participate more actively in the
      lysis of the necrotic tissues and wound cleaning than in the bacteria
      phagocytosis.

PMID- 1375826
TI  - Clinicopathologic correlation of occult choroidal neovascularization in age
      related macular degeneration.
AB  - We report the clinicopathologic features of an eye with occult choroidal
      neovascularization associated with age-related macular degeneration.
      Ophthalmoscopic findings at presentation included subretinal fluid and lipid. We
      noted angiographic staining of irregularly elevated areas of retinal pigment
      epithelium. In the late phase of the angiogram, fluorescein leakage at the level
      of the outer retina was observed that did not correspond to well-demarcated areas
      of hyperfluorescence in earlier phases. The patient was randomized to treatment
      in a pilot trial comparing the effects of grid laser treatment with the effects
      of no treatment for occult choroidal neovascularization. Three weeks after
      treatment, some of the subretinal fluid had cleared and vision improved. The
      patient died 6 weeks after laser treatment. Histopathologic study disclosed a
      subretinal pigment epithelial fibrovascular membrane. Neovascularization
      originated from the choroid.

PMID- 1375827
TI  - Transmission electron microscopic study of a subretinal choroidal neovascular
      membrane due to age-related macular degeneration.
AB  - From a patient with age-related macular degeneration we studied ultrastructurally
      a disciform scar that was removed from an eye with a vitreous hemorrhage. In
      cross section, the scar was divided by a retinal pigment epithelial (RPE) cell
      layer. The choroidal side consisted of fibrovascular tissue with active
      neovascular buds and inflammatory cells, including macrophages attached to the
      RPE basement membrane. Apart from the RPE, no components of Bruch's membrane
      could be identified. The retinal side contained organizing hemorrhage and a
      collagenous matrix with fibroblastlike cells probably of RPE and choroidal
      origin. The anatomy and the clinical findings at surgery suggest that such scars
      lie on (rather than within) the inner collagenous layer of Bruch's membrane and
      contain two components divided by the original RPE layer. The choroidal side is
      fibrovascular, including active neovascularization, and the retinal side is
      fibrous and formed by metaplastic RPE cells and choroidal fibrovascular ingrowth.

PMID- 1375828
TI  - Observing development through evolutionary eyes: a practical approach.
AB  - An argument is made that only through a detailed comparison of mutational
      mechanisms underlying the evolution of the genetic systems governing development,
      can the 'logic' of individual development be fully comprehended. To do this, it
      is essential to choose two or more genes (or their products) that interact in the
      establishment of a given function, and to compare the molecular basis of that
      interaction in closely related species. The rationale to this approach arises
      from observations of molecular co-evolution between interacting partners involved
      with given functions which have led to species specificity in the manner in which
      such functions are effected. Molecular coevolution reveals that divergence in
      sequence can be tolerated whilst biological functions are maintained, not because
      it is neutral and dispensable but because successful, compensatory changes can
      evolve in eukaryotic genomes that are in continuous states of flux.

PMID- 1375829
TI  - Binding of [3H]SCH23390 to a non-dopaminergic site in bovine kidney.
AB  - Binding of the D1 dopamine receptor antagonist [3H]SCH23390 to bovine renal
      cortical membranes has been studied. Specific binding of [3H]SCH23390 was
      saturable and reversible and stereoisomers of SCH23390 competed
      stereoselectively. In contrast, competition with the isomers of butaclamol was
      not stereoselective and dopamine failed to compete for the [3H]SCH23390 binding
      site. The site is therefore not a D1 dopamine receptor. Competition studies with
      a very wide range of compounds failed to define the nature of the [3H]SCH23390
      binding sites in renal cortex whereas in parallel studies the characteristics of
      [3H]SCH23390 binding in caudate nucleus were entirely consistent with those of D1
      dopamine receptors. The nature of [3H]SCH23390 binding in preparations of tubular
      and glomerular membranes was found to be virtually identical to those of crude
      renal cortical membranes indicating lack of compartmentation of these sites.
      Autoradiographic studies of [3H]SCH23390 binding in bovine kidney showed
      significantly higher levels of binding sites in renal cortex compared with renal
      medulla and this was confirmed by direct ligand binding studies.

PMID- 1375830
TI  - [Nursing care of the patient with an artificial pacemaker].
AB  - The construction of high technology electronic artificial cardiac pacemaker and
      its application by the medical science has changed the way and the prognosis of
      the diseases of the cardiac conducting system. Nursing presence is essential in
      care of the patient with a cardiac pacemaker. In the operating theatre the nurse
      creates the most ideal environment and assists at the application of the
      artificial pacemaker; in the ward she observes with watchful glance for
      prevention of complications providing individual and holistic nursing care, and
      helps the patient and his family with rehabilitation and adaptation to his new
      way of life. In addition, the nurse teaches the patient how to observe the
      function of his pacemaker, and emphasizes the importance of keeping the doctor's
      orders and regularly visiting the outpatients cardiac pacemakers control
      department to check his pacemaker.

PMID- 1375832
TI  - Fludarabine phosphate (Fludara).

PMID- 1375831
TI  - Cell-cell contact mechanisms.
AB  - Exciting new findings link characteristic properties of the inflammatory process
      previously not linked functionally. For example, it is now clear that oxygen
      radicals and leukocyte adhesion are intimately related in a carefully transduced
      and orchestrated series of events that culminates in release of granule contents,
      but not before the leukocyte has safely transversed the vessel wall. In addition
      to defining separate heterocellular contacts and homocellular aggregation we must
      now consider equilibrium events that allow associations among cell-cell
      partnerships involving different cell types.

PMID- 1375833
TI  - [Progressive aphasia: current status].

PMID- 1375834
TI  - [Stroke. Aphasia--like a lost card file. Interview by Siv Barstad].

PMID- 1375835
TI  - Coping with infertility: a new nursing perspective.
AB  - Infertility is a major life stressor, and reproductive failure is difficult to
      accept. Many couples become trapped in a cycle of repeated medical treatment,
      repeating painful patterns without developing insight or growth, feeling
      powerless to achieve their goal or move on. The causes of inappropriate coping
      behaviors are not well understood, and there is little direction for the nurse
      clinician's efforts to assist the couple with decision making. The use of
      superstition and ritual (magical thinking or magical ideation) by couples with
      infertility is discussed, and its role as a potential barrier to resolution is
      evaluated. A clinical tool for assessing the extent of magical ideation is
      described and its potential clinical utility explored. Women who have experienced
      a previous pregnancy may be more likely than nulliparas to substitute magical
      thinking for coping behaviors that might bring them closer to resolution.
      Problems with current research in this area are discussed, and directions for
      developing clinical nursing interventions are suggested.

PMID- 1375836
TI  - Intraocular gas effects on corneal endothelial permeability.
AB  - We examined the effects of intraocular gases on the permeability of the rabbit
      corneal endothelium to inulin and dextran. Volumes of air (0.16 ml), sulfur
      hexafluoride (SF6) (0.08 ml), and octafluoropentane (C3F8) (0.04 ml) were infused
      into the anterior chamber at constant intraocular pressure so that all volumes
      were equal after expansion. The inulin/dextran permeability was statistically
      decreased by infusion with Ringer, while air caused an 8.4% increase in dextran
      permeability but no effect on inulin flux. These small effects were of no
      biological significance. SF6 caused a 16% and 13% increase in inulin and dextran
      permeability, respectively, while C3F8 caused an 18% increase in both inulin and
      dextran permeability. Longevity of gas in the anterior chamber appears important
      in delineating the deleterious effects. The gases per se do not appear toxic but
      rather disrupt normal physiologic function through physical process.

PMID- 1375837
TI  - Alterations in lens permeability during galactose cataract development in rat.
AB  - Lens permeability has been shown to be compromised during galactose-induced
      cataract development in rats. Recent studies have demonstrated permeability and
      diffusion pathways as well as endocytotic activity in normal lenses of different
      species using tracers of different molecular weights. We investigated the
      permeability and diffusion of tracers in normal rat lenses and in lenses during
      cataract development using three different molecular weight tracers, lanthanum
      nitrate (LN, MW 430), ruthenium red (RR, MW 858.5) and horseradish peroxidase
      (HRP, MW 40.000) for this study. Sprague Dawley rats weighing 50gms were fed
      Purina Rat Chow with or without galactose. Our results, based on transmission
      electron microscopy, show that all tracers penetrated through the capsule and the
      basal portion of the intercellular spaces. While the diffusion of RR was
      restricted to the epithelial cell layer, LN and HRP were observed in
      intercellular spaces in cortical fiber cells. In the HRP "washout" studies, HRP
      could be readily removed from the intercellular spaces in the basal region in the
      epithelial cell layer. This and other observations suggest the presence of a
      barrier (tight-junction) in the apical region. Our studies also suggest an influx
      of tracers in the lens, specifically LN and HRP, through the equatorial region.
      The permeability of the tracers increased and endocytotic vesicles with tracers
      were often found associated with the lateral and basal membranes of epithelial
      cells in the galactose-fed rats at the precataractous and mature cataractous
      stages. This study provides further support for the presence of a tight-junction
      between epithelial cells and indicates the movement of tracers through the
      equatorial region. Moreover, it confirms previous observations that indicated
      alterations in lens permeability during galactose cataractogenesis.

PMID- 1375838
TI  - Carcinosarcoma of the breast. Immunohistochemical and ultrastructural studies.
AB  - A case of a carcinosarcoma in the breast of a 51-year-old woman is described. The
      tumor consisted of two diversely differentiated components with cells possessing
      epithelial and mesenchymal characteristics. Plenty of cytokeratin and CEA were
      immunohistochemically recordable from the carcinomatous component. Some
      neoplastic cells also stained positively for actin, S-100 protein and smooth
      muscle antigen. The sarcomatous component was positive only for vimentin.
      Electron microscopic analysis revealed presence of the following cell types:
      epithelial cells, myoepithelial cells and polymorphous mesenchymal cells.

PMID- 1375839
TI  - Effects of diets containing casein and rapeseed on enzyme secretion from the
      exocrine pancreas in the pig.
AB  - The effect of dietary protein on enzyme activity of pancreatic juice was studied
      in ten growing, castrated, Large White male pigs. Animals, fitted with permanent
      cannulas in the pancreatic duct and in the duodenum, were divided into two groups
      receiving either casein or rapeseed concentrate as a protein source. After a 15 d
      adaptation period to the experimental diet, the volume of pancreatic secretion
      was significantly higher, whereas the protein concentration was lower in the
      casein group compared with the rapeseed group. No statistical difference was
      observed in the daily protein output between groups. Total secreted activities of
      carboxypeptidase A (EC 3.4.17.1), and elastase (EC 3.4.21.36) were higher in the
      casein group during the nocturnal period, whereas total activities of trypsin (EC
      3.4.21.4), chymotrypsin (EC 3.4.21.1), carboxypeptidase B (EC 3.4.17.2) and
      amylase (EC 3.2.1.1) in pancreatic secretions during the post-prandial periods
      were increased by the ingestion of the rapeseed diet. It is concluded that the
      pancreatic enzyme secretion is sensitive to the nature of the protein ingested.

PMID- 1375840
TI  - A PML/retinoic acid receptor alpha fusion transcript is constantly detected by
      RNA-based polymerase chain reaction in acute promyelocytic leukemia.
AB  - The t(15;17) translocation is specifically observed in patients with
      promyelocytic leukemia (AML3). The chromosomal rearrangement juxtaposes the
      retinoic acid receptor alpha (RAR alpha) and PML genes, resulting in PML/RAR
      alpha fusion transcripts. Our previous studies have shown that a polymerase chain
      reaction (PCR) amplification product could be obtained from the cDNA of the NB4
      promyelocytic cell line from which the chimaeric PML/RAR alpha was cloned. We
      report here that in all 14 AML3 patients tested, reverse transcriptase-PCR (RT
      PCR) allows the detection of three specific fusion products. In eight patients,
      one amplification product was detected corresponding to the previously described
      abnormal fusion. Five patients displayed a different amplified fragment
      corresponding to a different fusion point. One other patient always showed a
      third different-sized product. The different types of fusion transcripts
      amplified were correlated to the size of the abnormal RAR alpha transcripts
      detected in these patients by Northern analysis, but did not prove determinant
      for either the phenotypic features or the retinoic acid responsiveness in AML3
      cells in this group of patients. The consistent identification by RT-PCR of the
      fusion of the PML and RAR alpha genes in AML3 patients suggest that this method
      will provide a useful tool for the diagnosis and detection of minimal residual
      disease in these patients.

PMID- 1375841
TI  - Effective immunochemotherapy of CALLA+C mu+ human pre-B acute lymphoblastic
      leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19)
      pokeweed antiviral protein immunotoxin plus cyclophosphamide.
AB  - A highly aggressive human CALLA+C mu+ pre-B acute lymphoblastic leukemia (ALL)
      cell line (NALM-6-UM1) causes disseminated and invariably fatal leukemia in CB.17
      mice with severe combined immunodeficiency (SCID). We used this SCID mouse model
      of human pre-B ALL to evaluate and compare, in a total of 434 SCID mice, the
      antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP)
      immunotoxin and cyclophosphamide (CPA) as individual reagents and as combined
      immunochemotherapeutic regimens. B43-PAP plus CPA was superior to either the
      immunotoxin or drug alone, and combined immunochemotherapy markedly improved the
      event-free survival (EFS) of SCID mice challenged with NALM-6-UM1 pre-B ALL
      cells. Notably, 90% to 100% of SCID mice challenged with 1 x 10(6) leukemia cells
      and then treated with B43-PAP plus CPA combined immunochemotherapy regimens
      became long-term survivors, a result not achieved with B43-PAP alone or CPA
      alone. The advantage was particularly evident in mice inoculated with 5 x 10(6)
      leukemia cells. While neither 15 micrograms B43-PAP (median survival, 58 days)
      nor 1 mg CPA (median survival, 49 days) resulted in long-term EFS of SCID mice
      challenged with 5 x 10(6) NALM-6-UM1 pre-B ALL cells, the probability of EFS at 6
      months was 50% +/- 16% for SCID mice treated with 15 micrograms B43-PAP plus 1 mg
      CPA (median survival, greater than 180 days) (P less than .0001). The probability
      of long-term EFS was only 14% +/- 7% for mice treated with 30 micrograms B43-PAP
      and 0% +/- 0% for mice treated with 1 mg CPA, but 40% +/- 16% for mice treated
      with 30 micrograms B43-PAP plus 1 mg CPA (P less than .0001). Similarly, the
      probability of EFS at 6 months was 40% +/- 16% for mice treated with 2 mg CPA
      alone, 70% +/- 15% for mice treated with 2 mg CPA plus 15 micrograms B43-PAP, and
      70% +/- 15% for mice treated with 2 mg CPA plus 30 micrograms B43-PAP. Ten SCID
      mice in the B43-PAP plus CPA combined immunochemotherapy arms surviving long term
      after the inoculation of 5 x 10(6) NALM-6-UM1 pre-B ALL cells were electively
      killed at 174 to 181 days to assess their leukemia burden. We found no evidence
      of leukemia in any of the bone marrow specimens by two-color immunofluorescence
      and multiparameter flow cytometry.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375843
TI  - Biologic significance of constitutive and subliminal growth factor production by
      bone marrow stroma.
AB  - The "stromal" or adherent cells of long-term murine Dexter explant bone marrow
      cultures provide the best in vitro model of the bone marrow microenvironment.
      Colony-stimulating factor-1 (CSF-1) is produced constitutively by these cells and
      is easily detected, but most investigators have not found constitutive production
      of the other hemolymphopoietic cytokines. We have previously reported the
      detection of granulocyte-macrophage-CSF (GM-CSF) in murine stromal cultures and
      its induction by the lectin Pokeweed mitogen. The present studies analyzing
      stromal cytokine messenger RNA (mRNA) production by standard Northern blot
      analysis show constitutive production of mRNAs for CSF-1, GM-CSF, granulocyte-CSF
      (G-CSF), c-kit ligand (KL), and interleukin-6 (IL-6), but not IL-3, IL-4, or IL-5
      by 3-week irradiated or nonirradiated murine Dexter stromal cells. Exposure of
      stromal cells to Pokeweed mitogen or IL-1 16 hours before RNA harvest induces the
      messages for GM-CSF, G-CSF, KL, and IL-6, but not IL-3, IL-4, IL-5, or CSF-1.
      Polymerase chain reaction amplification of cDNA made with reverse transcriptase
      from stromal RNA using two separate sets of IL-3-specific primers shows the
      presence of IL-3 message in irradiated stromal cells, which is only detectable
      with this more sensitive technique. The factor-dependent cell lines FDC-P1 and
      32D are supported by the stromal cells without the addition of exogenous growth
      factors, demonstrating a cytokine activity in these cultures that is inhibited by
      the addition of anti-IL-3 or anti-GM-CSF antibodies. These data indicate that
      murine Dexter stromal cells constitutively produce CSF-1, GM-CSF, G-CSF, IL-6,
      KL, and IL-3. This growth factor production could explain the support of
      granulocyte, macrophage, and megakaryocyte production and stem cell maintenance
      in Dexter-type long-term murine bone marrow cultures.

PMID- 1375842
TI  - Further phenotypic characterization and isolation of human hematopoietic
      progenitor cells using a monoclonal antibody to the c-kit receptor.
AB  - A mouse antihuman monoclonal IgG2a antibody, termed stem cell receptor-1 (SR-1),
      specific for a determinant of the c-kit ligand receptor (KR), was used as an
      immunologic probe to analyze KR expression by human bone marrow hematopoietic
      progenitor cells. Monoclonal antibodies to CD34 and HLA-DR were used in a
      multicolor staining protocol in conjunction with SR-1 to further define the
      phenotypes of various classes of hematopoietic progenitor cells. Expression of KR
      (SR-1+) on hematopoietic progenitor cells identified subpopulations of cells
      expressing CD34 (CD34+). While one-half of the CD34- and HLA-DR-expressing cells
      (CD34+ HLA-DR+) expressed the KR (SR-1+), one-third of the CD34+ cells that
      lacked HLA-DR expression (CD34+ HLA-DR-) were SR-1+. The CD34+ HLA-DR+ SR-1+ cell
      population contained the vast majority of the more differentiated progenitor
      cells, including the colony-forming unit (CFU) granulocyte-macrophage; burst
      forming unit-erythrocyte; CFU-granulocyte, erythrocyte, macrophage,
      megakaryocyte; and the CFU-megakaryocyte. The overall progenitor cell cloning
      efficiency of this subpopulation was greater than 31%. By contrast, the CD34+ HLA
      DR- SR-1+ cell population contained fewer of these more differentiated progenitor
      cells but exclusively contained the more primitive progenitor cells, the BFU
      megakaryocyte, high proliferative potential-colony-forming cell, and long-term
      bone marrow culture-initiating cell. The overall progenitor cell cloning
      efficiency of this subpopulation was greater than 7%. Both the CD34+ HLA-DR- and
      CD34+ HLA-DR+ cell subpopulations lacking KR expression contained few assayable
      hematopoietic progenitor cells. Long-term bone marrow cultures initiated with
      CD34+ HLA-DR- SR-1+ but not CD34+ HLA-DR- SR-1- cells, which were repeatedly
      supplemented with c-kit ligand (KL) and interleukin-3, generated assayable
      progenitor cells of at least 2 lineages for 10 weeks. These experiments
      demonstrate the expression of the KR throughout the hierarchy of human
      hematopoietic progenitor cell development. We conclude from our data that the KL
      and KR play a pivotal role in cytokine regulation of both the primitive and more
      differentiated human hematopoietic progenitor cells.

PMID- 1375844
TI  - Enhanced hematopoietic growth factor production in an experimental
      myeloproliferative syndrome.
AB  - The murine myeloproliferative syndrome induced by the myeloproliferative sarcoma
      virus (MPSV) has numerous similarities to human primary myelofibrosis. We have
      shown that medium conditioned by spleen cells of MPSV-infected mice has the
      capacity to support the growth of primitive blast cell colonies. The detection of
      this activity associated with MPSV infection stimulated us to characterize the
      hematopoietins responsible for this activity. Northern blot analysis showed a
      large increase, or induction, of interleukin-6 (IL-6), granulocyte-macrophage
      colony-stimulating factor (GM-CSF), macrophage-CSF (CSF-1), and granulocyte-CSF
      (G-CSF) transcripts in the hematopoietic organs of MPSV-infected mice; however,
      no IL-3 transcript could be detected in either MPSV-infected or normal mice.
      Significant levels of IL-1 alpha, IL-6, G-CSF, and CSF-1 bioactivities were found
      in the serum of MPSV-infected mice, but not in controls. Additionally, analysis
      of medium conditioned by spleen cells of MPSV-infected mice showed the presence
      of tumor necrosis factor alpha bioactivity. The increased production of cytokines
      that are able to stimulate pluripotent hematopoietic stem cells corroborates the
      hypothesis of a possible involvement of hematopoietic growth factors in the
      development of some myeloproliferative disorders.

PMID- 1375846
TI  - Suppressive effect of granulocyte-macrophage colony-stimulating factor on the
      generation of natural killer cells in vitro.
AB  - We investigated the effects of recombinant human granulocyte-macrophage colony
      stimulating factor (rhGM-CSF) and recombinant human granulocyte-CSF (rhG-CSF) on
      the generation of natural killer (NK) cells in vitro. NK cells were cultured from
      selected human bone marrow cells obtained after the elimination of mature T and
      NK cells. rhGM-CSF significantly suppressed the generation of CD56+ cells and NK
      activity (P less than .01) in a dose-dependent manner. The generation of large
      granular lymphocytes (LGL) was also suppressed in the presence of rhGM-CSF (P
      less than .01). In contrast, rhG-CSF had no effect on LGL (P greater than .05).
      Both rhGM-CSF and rhG-CSF had no influence on the CD56+ cell count in the
      peripheral blood. These results suggest that rhGM-CSF suppresses the in vitro
      generation of NK cells.

PMID- 1375845
TI  - Stem cell factor stimulates the in vitro growth of bone marrow cells from
      aplastic anemia patients.
AB  - Aplastic anemia (AA) is a rare human bone marrow disorder of unknown etiology
      manifested by a strongly impaired growth of hematopoietic precursors. In this
      study, we examined the ability of recombinant human stem cell factor (SCF) to
      stimulate proliferation in vitro of bone marrow cells from 15 AA patients. All
      patients had been previously treated with antilymphocyte globulin (ALG). SCF, in
      combination with erythropoietin (Epo), interleukin-3 (IL-3), granulocyte
      macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating
      factor (G-CSF), increased the number of hematopoietic colonies formed in a
      semisolid medium by AA marrows. Maximal colony numbers reached 30% of the numbers
      observed with normal bone marrow cells. Proliferation of AA cells cultured in a
      liquid medium containing SCF together with Epo, IL-3, GM-CSF, and G-CSF
      approached 70% of the control level, as measured by 3H-thymidine incorporation.
      The effect of the combination of SCF with the other growth factors was more than
      10 times stronger than that of the growth factors alone. The most marked effect
      of SCF was on the generation of erythroid colonies by precursor cells. The
      results demonstrate synergism between CSF and other hematopoietic growth factors,
      resulting in the most efficient stimulation of the in vitro growth of AA bone
      marrow cells described to date. Use of SCF, either alone or in combination with
      other factors, may be of potential value in treatment of AA.

PMID- 1375847
TI  - CD16- CD56+ natural killer cells after bone marrow transplantation.
AB  - Natural killer (NK) cells are phenotypically defined as lymphocytes expressing
      the antigens CD56 and mostly CD16 (Fc gamma RIII), but lacking CD3. A small CD3-
      CD16- CD56+ NK cell subset has been described in normal individuals representing
      less than 2% of peripheral blood lymphocytes. We analyzed here 70 patients for
      their reconstitution of the immune system during follow-up after autologous or
      allogeneic bone marrow transplantation. In 35% of these patients, two different
      NK cell subsets, namely CD56+dim and CD56+bright cells, were observed. The mean
      duration of these two subsets after transplant was 4 months. Sixty-five percent
      of the patients exhibited an increased number of NK cells, but only the typical
      CD16+ CD56+dim population. The CD56+bright subpopulation represented a particular
      CD3- CD16- NK subset, with posttransplant frequencies up to 70% of all NK cells
      and 40% of peripheral blood lymphocytes, respectively. In contrast to normal
      CD56+dim NK cells, CD56+bright cells coexpressed the activation antigens p75 beta
      chain of interleukin-2 receptor (IL-2R), CD2R, and CD26, but were negative for
      CD16. NK and antibody-dependent cellular cytotoxicity activity of CD56+bright
      cells was low compared with CD56+dim NK cells. But using IL-2 and interferon
      gamma, their cytotoxicity could be enhanced even more than in CD56+dim
      lymphocytes. These different subsets may reflect distinct activation or
      differentiation steps of NK cells during reconstitution of the immune system.
      Their differential response to IL-2 may be of functional importance for
      posttransplant cytokine therapy.

PMID- 1375849
TI  - Expression of the APO-1 antigen in Burkitt lymphoma cell lines correlates with a
      shift towards a lymphoblastoid phenotype.
AB  - APO-1 is a cell surface molecule that induces apoptosis when ligated with the
      monoclonal antibody anti-APO-1. Expression of APO-1 and response to anti-APO-1
      was investigated in a number of Epstein-Barr virus (EBV)-positive and -negative
      Burkitt lymphoma (BL) cell lines, in EBV-immortalized lymphoblastoid cell lines,
      and in cells from fresh BL biopsies. APO-1 was not expressed in EBV-negative cell
      lines and in EBV-positive BL cell lines with a phenotype corresponding to BL
      tumor biopsy cells (CD10+, CD21-, CD23-, CD30-, CD39-, CDw70-, CD77+).
      Accordingly, fresh BL cells obtained from three BL biopsies were APO-1 negative.
      EBV-positive BL cell lines that had acquired a lymphoblastoid phenotype (CD10-,
      CD21+, CD23+, CD30+, CD39+, CDw70+, CD77-) upon prolonged in vitro cultivation,
      as well as normal B-lymphoblastoid cell lines, expressed a high density of APO-1.
      APO-1 may, therefore, be regarded as a B-cell activation marker. APO-1 expression
      is not the only prerequisite for anti-APO-1-induced apoptosis because 6 of 7 APO
      1-expressing EBV-positive BL cell lines were not sensitive to anti-APO-1, whereas
      all lymphoblastoid cell lines were killed by anti-APO-1. The sensitivity of
      lymphoblastoid cell lines to anti-APO-1-mediated apoptosis may open a new
      therapeutic approach for the treatment of EBV-induced lymphoproliferative lesions
      in immunocompromised individuals, because these are composed of cells with a
      lymphoblastoid phenotype.

PMID- 1375848
TI  - Clinical and prognostic significance of monoclonal small cells in the peripheral
      blood and bone marrow of various B-cell lymphomas.
AB  - Discordant lymphomas, in particular nodal large-cell lymphomas with marrow small
      cell lymphoma, were discovered recently, and the prognosis of patients with such
      disease has been discussed. The small cells were reported to be small lymphocytic
      or small cleaved lymphoma cells. We have detected, by kappa-lambda imaging (KLI)
      with delta-curves, using a flow cytometer, small lymphoma cells in the peripheral
      blood (PB) and bone marrow (BM) of 41 untreated patients with various B-cell
      lymphomas expressing surface Ig (sIg+BCL), and evaluated their clinical and
      prognostic significance. Small cells were found in approximately 90% (37 of 41)
      of sIg+BCL patients when either PB or BM was analyzed and, overall, the presence
      of small cells correlated well with the disease activity. However, in some
      patients, a few cells remained in the PB (16%) or BM (27%) even when they were in
      remission, whereas in others, the cells were presented in the PB or BM several
      months before relapse. These results suggest that the detection of small cells in
      PB or BM by KLI may be helpful for screening and monitoring patients with
      sIg+BCL. When the patients were subdivided into three groups (normal, low, and
      high amplitude), according to the abnormal grade criteria of the delta-curves,
      which were based on the results of both PB-KLI and BM-KLI, the survival of the
      high-amplitude group tended to be shorter than that of the normal group (P =
      .068), which was particularly marked when the follow-up period exceeded 2 years.
      Moreover, as the group grading worsened (normal less than low less than high),
      the complete response rates deteriorated (100%, 71%, and 60%, respectively) and
      the respective relapse rates after complete remission increased (17%, 40%, and
      67%). Thus, the determination of the proportion of small lymphoma cells in PB and
      BM by KLI may be useful for predicting the prognoses of patients with sIg+BCL.

PMID- 1375850
TI  - Deletion of the zinc-binding motif of CD13/aminopeptidase N molecules results in
      loss of epitopes that mediate binding of inhibitory antibodies.
AB  - The myeloid cell-surface glycoprotein CD13/aminopeptidase N (APN; EC 3.4.11.2)
      contains a pentapeptide (HExxH) in its extracellular domain that is
      characteristic of many zinc-dependent metalloproteinases. This region contains
      residues important for zinc binding and constitutes part of the catalytic domain
      of several metalloproteases. We deleted an internal fragment of 117 base pairs
      (bp) from the human CD13/APN cDNA, resulting in an in-frame deletion that
      included the sequences coding for this pentapeptide motif. The mutant cDNA was
      subcloned into a retroviral expression vector, and polypeptides encoded by the
      altered cDNA were expressed in transfected murine NIH-3T3 fibroblasts. The mutant
      CD13/APN molecules lacked enzymatic activity, and their intracellular processing
      to the cell surface was retarded by comparison with normal CD13/APN polypeptides.
      The mutant molecules also lacked epitopes required for binding of four of 19 CD13
      specific monoclonal antibodies (MoAbs) tested in flow cytometric assays. Each of
      the four MoAbs also inhibited the enzymatic activity of wild-type APN molecules,
      suggesting that these antibodies may inhibit aminopeptidase activity by
      interfering with the enzyme's zinc-coordinating properties. Cells engineered to
      express mutant CD13/APN polypeptides at the cell surface provide a tool for
      defining the physiologic role of this enzyme on normal and malignant myeloid
      cells and marrow stromal cells.

PMID- 1375851
TI  - Developmental hierarchy during early human B-cell ontogeny after autologous bone
      marrow transplantation using autografts depleted of CD19+ B-cell precursors by an
      anti-CD19 pan-B-cell immunotoxin containing pokeweed antiviral protein.
AB  - Sequential immunophenotypes of bone marrow (BM) and peripheral blood (PBL)
      lymphoid cells from 15 B-lineage acute lymphoblastic leukemia (ALL) patients who
      underwent autologous bone marrow transplantation (BMT) during complete remission
      were determined by dual-color immunofluorescence and multiparameter flow
      cytometry. Autografts were depleted of CD19+ B-cell precursors by an
      immunochemopurging protocol that combines B43-PAP, a potent anti-CD19
      immunotoxin, and the cyclophosphamide congener 4-hydroperoxycyclophosphamide (4
      HC). A marked interpatient variation was observed in the appearance and expansion
      of B-cell precursors repopulating the posttransplant marrow. The expression of
      CD10 and CD19 antigens during early B-cell ontogeny post-BMT preceded the
      expression of CD20, CD21, CD22, CD40, and sIgM. The surface antigen profiles of
      the emerging B-cell precursors were similar to those of fetal liver or fetal bone
      marrow B-cell precursors. Our comparisons of BM and PBL samples from patients in
      the early post-BMT period demonstrated that (1) PBL initially contains fewer B
      lineage cells than does BM, and (2) circulating B-lineage lymphoid cells have a
      more mature immunophenotype than do BM B-lineage lymphoid cells. Comparison of
      the surface antigen profiles of day 30 versus day 100 or year 1 BM or PBL
      lymphoid cells showed an increase in the percentages of CD10+CD22-
      undifferentiated lymphocyte precursors, as well as CD19+sIgM- B-cell precursors
      (pre-pre-B), consistent with a time-dependent expansion of these B-cell precursor
      populations post-BMT. Importantly, the percentages of CD10+CD22+ and CD19+sIgM+ B
      cell precursor (pre-B) populations also increased between 30 days and 1 year post
      BMT, confirming the ability of emerging immature B-cell precursors to
      differentiate along the B-precursor pathway. The acquisition and expression of B
      lineage differentiation antigens at different stages of the post-BMT B-cell
      ontogeny support the notion that the expression of these antigens is
      developmentally programmed. Similar to patients in previous autologous BMT
      studies, recipients of B-cell precursor-depleted autografts had normal or nearly
      normal serum immunoglobulin levels, suggesting that the maturing B-cell/plasma
      cell populations can produce and secrete immunoglobulins. The development of a
      functional CD19+ B-lineage lymphoid compartment in recipients of autografts which
      were depleted of CD19+ B-cell precursors corroborates the previously postulated
      existence of CD19- B-lineage lymphoid progenitor cells.

PMID- 1375852
TI  - In vivo sensitization of human lung carcinoma to bleomycin by the cysteine
      proteinase inhibitor E-64.
AB  - We recently demonstrated that the cysteine proteinase inhibitor, E-64, sensitizes
      human Burkitt's lymphoma (Daudi) to the antitumor action of bleomycin (BLM) by
      blocking its metabolism. We now report that E-64 sensitizes the BLM resistant
      human lung carcinoma A-549 by a mechanism unrelated to the inhibition of BLM
      metabolism. Treatment of A-549 tumor-bearing nude mice with either BLM (10 mg/kg)
      or E-64 (40 mg/kg) every other day for 10 days did not inhibit tumor growth.
      However, a 30 min pretreatment with E-64 prior to BLM caused complete and
      sustained inhibition of tumor growth. In contrast to our results with Burkitt's
      lymphoma, E-64 did not inhibit BLM metabolism but rather enhanced the tumor
      accumulation of BLM; within 10 min of BLM administration, tumors from E-64
      pretreated mice showed a 6-fold higher accumulation of BLM A2 compared to non
      pretreated xenografts. Furthermore, the level of tumor-associated BLM A2 remained
      2-fold higher in E-64 pretreated mice 20 and 30 min after BLM administration. In
      E-64 pretreated mice, the plasma level of BLM was increased by 2-fold. These
      results demonstrate that the cysteine proteinase inhibitor, E-64, sensitized
      human lung carcinoma A-549 to BLM and, contrary to the expected mechanism, this
      effect of E-64 was not related to the inhibition of BLM metabolism.

PMID- 1375853
TI  - Angiogenesis and basic fibroblast growth factor.

PMID- 1375854
TI  - The effects of vesamicol on trains of endplate currents and on focally recorded
      nerve terminal currents at mammalian neuromuscular junctions.
AB  - 1. The effects of vesamicol, an inhibitor of vesicular acetylcholine (ACh)
      storage, were studied on trains of endplate currents (e.p.cs) in the cut rat
      hemidiaphragm nerve-muscle preparation and on trains of focally recorded nerve
      terminal current waveforms in the mouse triangularis sterni nerve-muscle
      preparation. 2. In the rat, 0.1 and 1 microM (-)-vesamicol produced an
      enhancement of the rundown of e.p.c. amplitudes during trains of high frequency
      (50 Hz) nerve stimulation. However, 1 microM (+)-vesamicol had no effect on the
      rundown of e.p.c. amplitudes. 3. In the mouse, high concentrations of (-)
      vesamicol (10-100 microM) produced a concentration- and stimulation-dependent
      decrease in the amplitude of the second negative-going deflection of focally
      recorded nerve terminal current waveforms. 4. At 1 mM, (-)-vesamicol produced a
      stimulation-independent decrease in the amplitude of the first negative-going
      deflection of the nerve terminal current waveforms, an increase in signal delay
      and evidence of nerve conduction failure. These all indicate a local anaesthetic
      like block of nodal Na(+)-channels. 5. In contrast to its effects on trains of
      e.p.cs, the effects of vesamicol on the nerve terminal current waveforms were not
      stereoselective, the (+)-isomer being equipotent with the (-)-isomer. 6. Low
      concentrations of the Na(+)-channel blocking toxin, tetrodotoxin (15-60 nM),
      produced similar changes in the focally recorded nerve terminal current waveforms
      to those seen with vesamicol. 7. It is concluded that the stereoselective rundown
      of e.p.c. amplitudes produced by (-)-vesamicol is due to an effect, either direct
      or indirect, on ACh mobilization within motor nerve terminals. Furthermore, in
      mammalian species, the inhibitory effects of vesamicol on nodal Na+-channels
      which are seen at high concentrations do not contribute to the principal
      neuromuscular effects of the compound.

PMID- 1375855
TI  - X-irradiation attenuates relaxant responses in the rabbit ear artery.
AB  - 1. The relaxant actions of acetylcholine, substance P and calcitonin gene-related
      peptide, and the levels of neuropeptide Y and calcitonin gene-related peptide
      were assessed in the rabbit central ear artery 1, 4 and 6 weeks after a single
      dose of 45 Gy X-irradiation, a dose similar to that used clinically in
      intraoperative radiotherapy. 2. Relaxant responses induced by acetylcholine and
      substance P (both endothelium-dependent) and calcitonin gene-related peptide
      (endothelium-independent) were reduced, and endogenous neuropeptide Y and
      calcitonin gene-related peptide levels were unaffected after X-irradiation. 3.
      The mechanism(s) by which a single dose of 45 Gy X-irradiation may selectively
      damage relaxant, but not direct, contractile responses of the smooth muscle (as
      we have shown previously) of the rabbit central ear artery are discussed.

PMID- 1375857
TI  - The selective NK3 receptor agonist senktide excites a subpopulation of dopamine
      sensitive neurones in the rat substantia nigra pars compacta in vitro.
AB  - Intra- and extracellular recordings were made from substantia nigra zona compacta
      neurones from an in vitro rat brain slice preparation. A subpopulation of
      dopamine-sensitive neurones were encountered which were potently excited by bath
      application of the NK3 receptor agonist, senktide. On these senktide-sensitive
      neurones, NK1 and NK2 receptor agonists were inactive. The excitatory action of
      senktide supports a role for tachykinins as putative neurotransmitters in the
      basal ganglia.

PMID- 1375856
TI  - Involvement of capsaicin-sensitive neurones in the haemodynamic effects of
      exogenous vasoactive peptides: studies in conscious, adult Long Evans rats
      treated neonatally with capsaicin.
AB  - 1. The regional haemodynamic effects of i.v. bolus injections of bradykinin (0.05
      or 0.5 nmol), cholecystokinin (0.175 or 1.75 nmol), substance P (0.01 or 0.1
      nmol) and calcitonin gene-related peptide (0.05 or 0.5 nmol) were assessed in
      conscious, adult Long Evans rats that had been treated neonatally with either
      capsaicin (50 mg kg-1, s.c.) or vehicle. 2. In vehicle-treated rats, both doses
      of bradykinin were without effect on blood pressure, but caused tachycardia and
      hindquarters vasodilatation. Moreover, after the higher dose there were
      dilatations in the renal and superior mesenteric vascular beds. In capsaicin
      treated rats the hindquarters vasodilator effects elicited by both doses of
      bradykinin were significantly reduced, while the tachycardia and responses in the
      renal and superior mesenteric vascular beds were unchanged. 3. In vehicle-treated
      rats, cholecystokinin caused dose-dependent increases in blood pressure
      accompanied by renal, superior mesenteric and hindquarters vasoconstriction
      followed, after the higher dose, by a hindquarters vasodilatation. The lower dose
      produced a tachycardia, while there was a bradycardia followed by a tachycardia
      after the higher dose. In capsaicin-treated rats, the pressor response, as well
      as the renal vasoconstrictor effects of cholecystokinin, were greater than in
      vehicle-treated rats, while the heart rate, superior mesenteric or hindquarters
      responses were not different. 4. In vehicle-treated rats, substance P produced a
      dose-dependent depressor response and tachycardia accompanied by dilatations in
      the renal and hindquarters vascular beds and constriction in the superior
      mesenteric vascular bed. In capsaicin-treated rats, the responses to the lower
      dose of substance P were not different from those in vehicle-treated rats, while
      the depressor response to the higher dose of substance P was slightly less than
      in vehicle-treated rats and the renal vasodilatation was absent.5. In vehicle
      treated rats, calcitonin gene-related peptide caused dose-dependent hypotensive
      and tachycardic effects associated with dilatations in renal and hindquarters
      vascular beds and a constriction in the superior mesenteric vascular bed. After
      the higher dose, the renal vasodilatation was followed by a modest
      vasoconstriction. In capsaicin-treated rats, the depressor responses to both
      doses of calcitonin generelated peptide were slightly more prolonged than in
      vehicle-treated animals, whereas the heart rate and renal and mesenteric vascular
      conductance changes were not significantly different. However, there was a more
      sustained hindquarters vasodilator response to the higher dose of calcitonin gene
      related peptide in the capsaicin-treated rats.6. The results suggest that
      peripheral, capsaicin-sensitive neurones are involved in the cardiovascular
      responses to exogenous bradykinin and cholecystokinin in conscious rats. It does
      not appear that the extent of involvement of these neurones is underestimated on
      account of development of marked supersensitivity to the peptides they normally
      release, since responses to such peptides (e.g. substance P and calcitonin gene
      related peptide) are relatively normal in capsaicin-treated rats.

PMID- 1375858
TI  - Role of muscarinic receptor subtypes in central antinociception.
AB  - 1. The ability to modify the pain threshold by the two M1-muscarinic agonists:
      McN-A-343 and AF-102B and by the specific M2-agonist arecaidine was examined in
      mice and rats by using three different noxious stimuli: chemical (writhing test),
      thermic (hot-plate test) and mechanical (paw pressure test). 2. In the mouse hot
      plate test McN-A-343 (20-50 micrograms per mouse i.c.v.) and AF-102B (1-10 mg kg
      1 i.p.) produced significant antinociception which was prevented by atropine (1
      microgram per mouse i.c.v.) and by the two selective M1 antagonists: pirenzepine
      (0.01 micrograms per mouse i.c.v.) and dicyclomine (0.08 micrograms per mouse
      i.c.v. or 10 mg kg-1 i.p.) but not by the specific M2-antagonist AFDX-116 (0.1
      micrograms per mouse i.c.v.), naloxone (1 mg kg-1 i.p.) or by the acetylcholine
      (ACh) depletor hemicholinium-3 (HC-3) (1 micrograms per mouse i.c.v.). McN-A-343
      and AF-102B were able to increase the pain threshold also in the mouse acetic
      acid writhing test and in rat paw pressure test. These antinociceptive effects
      were completely prevented by dicyclomine (0.08 micrograms per mouse i.c.v. or 10
      mg kg-1 i.p.) but not by AFDX-116 (0.1 microgram per mouse or rat i.c.v.). 3. In
      contrast with the M1-agonists, the M2-agonist arecaidine (0.1-2 micrograms per
      mouse or rat i.c.v.) did not induce antinociception in all three analgesic tests.
      However, arecaidine, at the same i.c.v. doses, was able to reduce the pain
      threshold in the hot-plate and paw pressure tests.4. The site of muscarinic
      control of the pain threshold is localized in the CNS since drugs which do not
      cross the blood-brain barrier such as McN-A-343, pirenzepine and arecaidine
      exerted their effects only if injected i.c.v.5. On the basis of the above
      findings and existing literature we suggest that the postsynaptic muscarinic
      receptors involved in antinociception belong to the M1 subtype. Nevertheless,
      presynaptic autoreceptors (M2 subtype) may play a role in pain regulation since
      they are involved in modulation of endogenous ACh release.

PMID- 1375859
TI  - Effects of acromelic acid A on the binding of [3H]-kainic acid and [3H]-AMPA to
      rat brain synaptic plasma membranes.
AB  - 1. The ability of acromelic acid A to inhibit [3H]-kainic acid and [3H]-(RS)
      alpha-amino-3-hydroxy-5-methyloxazole-4-propionic acid ([3H]-AMPA) binding to rat
      brain synaptic plasma membranes was investigated by equilibrium radioligand
      binding assay. 2. Kinetic analysis of [3H]-kainic acid binding demonstrated the
      existence of two kainate binding sites in this tissue preparation and yielded
      equilibrium dissociation constants for [3H]-kainic acid of KD = 0.4 nM and KD =
      20.8 nM. 3. Kainic acid and domoic acid both appeared to displace [3H]-kainic
      acid from a single binding site with equilibrium binding constants of KD = 19.4
      nM and Ki = 14.5 nM respectively. Acromelic acid A exhibited a biphasic
      inhibition of [3H]-kainic acid binding to synaptic membranes with binding
      affinities of Ki = 15.1 nM and Ki = 1.49 microM. 4. In the absence of chaotropic
      ions, the order of potency of inhibition of [3H]-AMPA binding was acromelic acid
      A (Ki = 26 nM) greater than AMPA (KD = 184 nM) greater than domoic acid (Ki = 499
      nM). 5. The inclusion of 100 mM thiocynanate ion in the [3H]-AMPA binding assay
      resulted in a change in the order of potency to: AMPA (KD = 160 nM) greater than
      acromelic acid A (Ki = 289 nM) greater than domoic acid (Ki = 9.02 microM). 6.
      These results show that acromelic acid A distinguishes two kainate binding sites
      in rat brain synaptic plasma membranes and in addition, that in the absence of
      chaotropic ions, acromelic acid A is the most potent displacer of [3H]-AMPA
      binding yet described.

PMID- 1375861
TI  - Effects of self- and cross-reinnervation on the numbers of motoneurons
      regenerating to forearm muscles in young and adult rats.
AB  - The present study was carried out to compare the ability of motoneurons to
      regenerate to functionally appropriate and inappropriate muscles, following
      axotomy at different stages of postnatal development. Five-, 10-, 21-day-old and
      adult rats of both sexes were used. In one group, the right median and radial
      nerves were cut and reunited. In a second group, the cut nerves were cross
      reunited and, in a third group the nerves were merely exposed. Following survival
      periods of up to one year, the extent of motoneuron regeneration through the
      repaired nerves was determined by injecting the retrogradely transported tracers
      horseradish peroxidase (HRP) and Fast Blue into the flexor and extensor muscles
      of the right forearm. The results were expressed in terms of the difference
      between the number of labelled motoneurons on the experimental side of the spinal
      cord and the number on the control side, the latter having been labelled by
      injection of HRP and Fast Blue into the muscles of the left forearm. Comparisons
      were then made between the groups with respect to the age at which axotomy
      occurred, and the target of regeneration. The results showed that when axotomy
      was performed in 5- and 10-day-old rats, significantly fewer motoneurons were
      labelled, irrespective of whether or not the target was functionally appropriate,
      than when axotomy was performed in adulthood. The difference was most likely due
      to a lower survival rate of motoneurons following axotomy in neonates. No
      difference was found, however, between the numbers of labelled median and radial
      nerve motoneurons following self- versus cross-reinnervation in any age group.
      This suggests that, in both adult and neonatal rats, motoneurons which survive
      axotomy are able to regenerate equally well to functionally appropriate or
      inappropriate muscles.

PMID- 1375860
TI  - Projection neurons of the basolateral amygdala: a correlative Golgi and
      retrograde tract tracing study.
AB  - This study analyzed the projection neurons of the anterior subdivision of the rat
      basolateral amygdaloid nucleus (BLa) by correlating the morphology of Golgi
      stained neurons with the morphology of neurons that were retrogradely labeled by
      injections into the main terminal fields of BLa. In each animal multiple
      injections of horseradish peroxidase (HRP) and wheat germ agglutinin-conjugated
      HRP were made into the prefrontal cortex and rostral striatum. These injections
      labeled approximately 85% of BLa neurons. The great majority of labeled neurons
      were the same shape and relative size as the pyramidal (class I) neurons
      described in previous Golgi studies. The unlabeled neurons appeared to correspond
      to the nonpyramidal (class II and class III) neurons described in Golgi studies.
      Thus this investigation provides experimental evidence that the pyramidal neurons
      are the main projection neurons of BL, whereas most of the nonpyramidal cells are
      local circuit neurons.

PMID- 1375863
TI  - Intensification of labelings of the immunogold silver staining method by gold
      toning.
AB  - We evaluated the applicability of the gold toning procedure to the immunogold
      silver staining method using monoclonal antibody against dopamine. Immunolabeling
      was examined in the rat substantia nigra at light and electron microscopic
      levels. Vibratome sections of fixed midbrains were incubated with anti-dopamine
      antiserum and then with 5 nm colloidal gold bound to goat anti-mouse
      immunoglobulin. Silver staining of these sections produced a light brown
      immunolabeling. After the sections were processed by gold toning, the labeling
      became intense black. At a light microscopic level, these high contrast signals
      were retained after the sections were osmicated and embedded in Epon. At an
      electron microscopic level, signal-to-noise ratio was high, and the positive
      staining could easily be verified at a low-power magnification. The technique
      described here, the gold-toned immunogold silver staining method, provides high
      contrast signals and is much more sensitive than immunogold silver staining
      alone. This method, therefore, has great potential for use in immunohistochemical
      analysis of the central nervous system.

PMID- 1375862
TI  - Brain dopamine D-2 receptor mechanisms in spontaneously hypertensive rats.
AB  - Brain dopaminergic function was studied in spontaneously hypertensive rats (SHR)
      with the selective dopamine D-2 antagonist sulpiride. Sulpiride dose-dependently
      inhibited locomotor activity of normotensive Wistar-Kyoto rats (WKY). SHR showed
      an increase in locomotor activity in response to low doses of sulpiride, whereas
      no effect was observed of higher doses. In a two-bottle salt-preference test, WKY
      showed increased preference for an 0.9% saline solution after treatment with
      sulpiride, whereas total fluid intake remained the same. In SHR, sulpiride
      influenced neither salt-preference nor total fluid intake. SHR and WKY with a
      unilateral lesion of the median forebrain bundle showed similar turning behaviour
      in response to treatment with amphetamine. Pretreatment with 100 mg/kg sulpiride
      virtually abolished amphetamine-induced turning in WKY, but had little effect in
      SHR. Sulpiride dose-dependently increased serum prolactin concentrations in WKY
      and SHR. However, the increase was significantly greater in SHR. Dopamine D-2
      receptor binding was measured with in vitro autoradiography, using [125I]
      sulpiride as the ligand. Binding density was similar in the caudate nucleus and
      substantia nigra of SHR and WKY brain. Concentrations of the dopamine metabolites
      DOPAC and HVA, but not of dopamine itself, were significantly increased in
      frontal cortex, striatum and hypothalamus after treatment with 100 mg/kg
      sulpiride. There were no significant differences between SHR and WKY in the
      increase in the DOPAC/DA and HVA/DA ratio. These data show that SHR show
      differential changes in their response to central dopamine D-2 blockade when
      compared to WKY. Thus, in some tests (locomotor activity after high doses, salt
      preference, turning behaviour), SHR respond less to sulpiride.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1375864
TI  - Species differences in the immunophenotype of osteoclasts and mononuclear
      phagocytes.
AB  - Human osteoclasts, in contrast to mononuclear phagocytes, are known to express a
      well-defined restricted range of myeloid antigens. To determine whether these
      antigenic differences are present in other species, we examined the
      immunophenotype of chicken and rabbit osteoclasts, macrophages, macrophage
      polykaryons, and monocytes and compared them with similarly derived and cultured
      human cells. Human, rabbit, and avian osteoclasts reacted with monoclonal
      antibodies against human beta 1 integrins (CD29, CD49b, CD49d), beta 3 integrins
      (CD51, CD61), as well as human macrophage-associated antigen CD68. Avian
      osteoclasts also reacted for CD11a/18 and CD14 which are not present on human
      osteoclasts. Avian and mammalian monocytes, macrophages, and macrophage
      polykaryons expressed all the above antigens. Both avian and human macrophage
      polykaryons produced by culture of peritoneal macrophages reacted with anti-CD51
      antibodies indicating that expression of the vitronectin receptor alone does not
      distinguish between these cells in vitro.

PMID- 1375866
TI  - Metabolism and nucleic acid binding of N-hydroxy-4-acetylaminobiphenyl and N
      acetoxy-4-acetylaminobiphenyl by cultured human uroepithelial cells.
AB  - Metabolic activation of N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy
      4-acetylaminobiphenyl (N-OAc-AABP), the proximate carcinogenic metabolites of the
      human bladder carcinogen 4-aminobiphenyl (ABP), was examined in human
      uroepithelial cells (HUC). Bioconversion was studied by incubating HUC cultures
      with [3H]N-OAc-AABP or [3H]N-OH-AABP. Three organo-soluble metabolites, N-OH
      AABP, 4-acetylaminobiphenyl (AABP), and ABP were identified in ethyl acetate
      extracts from cultures exposed to N-OAc-AABP. Similarly, AABP and ABP were
      characterized as the major metabolites from cultures treated with N-OH-AABP.
      Incubation of N-OAc-AABP with HUC microsomes in vitro yielded primarily the O
      deacetylation product N-OH-AABP. The HUC microsomes also catalyzed the N
      deacetylation of N-OAc-[14C]AABP, N-OH-[14C]AABP, and [3H]AABP. The O- and N
      deacetylase activities for N-OAc-AABP were 55.9 and 38.2 nmol/mg/min,
      respectively. These O- and N-deacetylase activities were both blocked by
      paraoxon. Incubation of [3H]N-OAc-AABP or [3H]N-OH-AABP with HUC microsomes and
      tRNA or DNA showed that 23.0 and 8.0 nmol of N-OAc-AABP and 74.5 and 25.2 pmol of
      N-OH-AABP were bound per mg protein/mg RNA or DNA, respectively. In comparison,
      the acetyl CoA-dependent HUC cytosol-mediated bindings of [3H]N-OH-ABP to RNA and
      DNA were 801 and 447 pmol/mg nucleic acid/mg protein. The HUC microsome-mediated
      bindings of N-OAc-AABP and N-OH-AABP to nucleic acids were inhibited by paraoxon,
      whereas the cytosol-mediated binding of N-OH-ABP was insensitive to paraoxon
      inhibition. Chromatography of the DNA hydrolysate obtained from the in vitro
      incubation of [3H]N-OAc-AABP or [3H]N-OH-AABP with HUC microsomes showed N
      (deoxyguanosine-8-yl)-4-aminobiphenyl as the major adduct, based on comparison
      with authentic synthetic standard. These results show that human uroepithelia
      contain microsomal acetyl transferases that are capable of converting the
      proximate metabolites N-OAc-AABP and N-OH-AABP of the human bladder carcinogen
      ABP, to reactive electrophiles that bind to DNA. The occurrence of these acetyl
      transferases in the target organ of the human bladder carcinogen ABP suggests
      that metabolic activation of some proximate metabolites of ABP could occur
      directly in HUC and could play a pivotal role in susceptibility to aryl
      amine/acetamide induced human bladder cancers.

PMID- 1375867
TI  - Estimation of prostatic growth using serial prostate-specific antigen
      measurements in men with and without prostate disease.
AB  - Prostate growth curves were estimated from serial prostate-specific antigen (PSA)
      measurements on frozen sera in three groups of men: (a) 16 men with no prostatic
      disease by urological history and examination; (b) 20 men with a histological
      diagnosis of benign prostatic hyperplasia (BPH) who had undergone simple
      prostatectomy; and (c) 18 men with a histological diagnosis of prostate cancer.
      The median number of repeated PSA measurements over an 8- to 26-yr period prior
      to histological diagnosis or exclusion of prostate disease was eight and 11 for
      noncancer and cancer subjects, respectively. Predicted rates of change in PSA
      (PSA velocity) were linear and curvilinear for control and BPH subjects,
      respectively. Subjects with cancer demonstrated both a linear and an exponential
      phase of PSA velocity. Based on time to double PSA, we estimated the epithelial
      doubling time for men without prostate disease to range from 54 +/- 13 yr at age
      40 to 84 +/- 13 yr at age 70. For men with BPH, doubling times ranged from 2 +/-
      13 yr at age 40 to 17 +/- 5 yr at age 85. Subjects with local/regional and
      advanced/metastatic cancer had similar PSA doubling times of 2.4 +/- 0.6 yr and
      1.8 +/- 0.2 yr, respectively. These data are consistent with what is known about
      prostatic growth with age in men without prostate disease and BPH, and the
      kinetics of prostate cancer growth. Estimates of prostatic growth rate from
      changes in PSA may be useful clinically in management of men with prostate
      disease.

PMID- 1375868
TI  - Growth inhibition by cholera toxin of human lung carcinoma cell lines:
      correlation with GM1 ganglioside expression.
AB  - The effect of cholera toxin (CT) on the growth of 12 small cell lung carcinoma
      (SCLC) and 15 non-small cell lung carcinoma (NSCLC) cell lines is presented. CT
      inhibited the growth of nine SCLC cell lines (concentration for 50% inhibition of
      growth, 27-700 ng/ml), all of which had abundant expression of GM1 ganglioside,
      the surface receptor for CT. CT-resistant SCLC all had greatly decreased GM1
      expression. In contrast, CT inhibited the growth of only four of 15 NSCLC cell
      lines. Seven of the 11 CT-resistant NSCLC had levels of GM1 comparable to CT
      sensitive NSCLC or SCLC. In a limited panel of cell lines, cyclic AMP (cAMP)
      agonists including forskolin, 8Br[cAMP], and dibutyryl[cAMP] did not consistently
      reproduce CT-mediated inhibition of cell growth, nor did these compounds overcome
      resistance of cells to the growth inhibitory effects of CT. Expression of the RI
      and RII regulatory subunits of cAMP-dependent protein kinase was similar in CT
      resistant and CT-sensitive SCLC or NSCLC cell lines. In the presence of
      isobutylmethylxanthine, intracellular cAMP levels induced by CT in a CT
      resistant, GM1(+) NSCLC cell line were comparable to those achieved in a CT
      sensitive NSCLC cell line. We conclude that inhibition of lung carcinoma cell
      growth by CT in all cases requires expression of GM1, and in the case of SCLC
      cell lines the presence of GM1 is sufficient. In NSCLC cell lines, expression of
      GM1 is not sufficient for growth inhibition by CT. These findings imply
      refractoriness to growth inhibition by cAMP in GM1(+), CT-resistant NSCLC cell
      lines and the possibility of non-cAMP-related mechanisms for growth inhibition in
      CT-sensitive cell lines.

PMID- 1375865
TI  - In vitro formation of mineralized nodules by periodontal ligament cells from the
      rat.
AB  - The purposes of this study were to determine whether periodontal ligament (PDL)
      cells are capable of producing mineralized nodules in vitro and to analyze
      ultrastructural features of the nodules. Rat PDL cells were obtained from
      coagulum in the socket at 2 days after tooth extraction and cultured at
      confluence in standard medium containing Dulbecco's Modified Eagle's Medium
      supplemented with 10% FBS and antibiotics. To test mineralized nodule formation,
      cells were further cultured for an additional 3 weeks in the standard medium
      containing (1) ascorbic acid (50 micrograms/ml) and sodium beta-glycerophosphate
      (10 mM), (2) ascorbic acid, sodium beta-glycerophosphate, and dexamethasone (5
      microM), or (3) ascorbic acid alone. Cells were then fixed in 2.5%
      glutaraldehyde, postfixed in 1% OsO4, and prepared for light and electron
      microscopy. Three-dimensional nodules containing mineralized matrices were formed
      only when the cells were cultured in the presence of ascorbic acid and
      dexamethasone. They were composed of multilayered fibroblasts (up to 13 layers),
      and highly organized collagen fibrils with 64 nm cross-banding patterns between
      the cell layers. The fibroblasts in the nodules exhibited an elongated shape with
      a high degree of cytoplasmic polarity throughout the nodule, and have the
      morphological features of PDL fibroblasts as seen in vivo. Mineral deposition
      with needle-like crystals was initiated on collagen fibrils located in
      intercellular spaces of the upper cell layers and became increasingly heavier
      towards the bottom half of the nodules. X-ray microanalysis and electron
      diffraction analysis confirmed that mineral deposition contained calcium and
      phosphate in the form of immature hydroxyapatite.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1375870
TI  - Recombinant human stem cell factor stimulates growth of a human glioblastoma cell
      line expressing c-kit protooncogene.
AB  - The growth of a panel of eight different human glioblastoma cell lines was
      examined in a human tumor cloning assay in agar, a tritiated thymidine uptake
      assay, and by counting cell numbers, in cultures performed in the absence or
      presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem
      cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and
      reproducibly affected by recombinant human SCF. However, growth of the CRL 1620
      cell line could be stimulated up to 5-fold by the cytokine. In contrast to the
      other cell lines investigated, CRL 1620 expressed the c-kit protooncogene
      assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of
      CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data
      suggest that SCF can be operative in growth modulation of malignant cells outside
      the hematopoietic system, and this finding should be further studied for its
      possible clinical implications.

PMID- 1375869
TI  - Dissociation of sensitivities to tumor promotion and progression in outbred and
      inbred SENCAR mice.
AB  - The sensitivity of outbred SENCAR mice and inbred SENCAR (SSIN) mice to
      multistage carcinogenesis was studied. Tumors were induced using either 7,12
      dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine as initiators
      and 12-O-tetradecanoylphorbol-13-acetate or benzoyl peroxide as promoting agents.
      Although the number of papillomas per mouse was higher in SSIN than in outbred
      SENCAR mice, the number of carcinomas observed in the SSIN strain was
      significantly lower regardless of the initiator or promoter used. It was also
      observed that the expression of markers of premalignant progression (i.e.,
      dysplasia, expression of keratin K13, and loss of keratin K1 expression) was
      markedly suppressed in SSIN papillomas. After 50 wk of promotion with 12-O
      tetradecanoylphorbol-13-acetate, the pattern of expression of K13 and K1 in SSIN
      mice was comparable to the pattern observed in outbred SENCAR mice after 10 to 20
      wk of promotion with 12-O-tetradecanoylphorbol-13-acetate. It was also observed
      that 67% of the tumors induced in SSIN mice by initiation with 7,12
      dimethylbenz[a]anthracene exhibited a mutation in codon 61 of the Ha-ras-1 gene.
      This latter finding suggests that the differences observed in tumor progression
      between the inbred strain and the outbred stock are not related to a genetic
      alteration in the Ha-ras-1 gene but rather to an independent event that we have
      postulated to involve a putative suppressor gene. The data reported here suggest
      that the putative gene(s) that confers susceptibility to tumor promotion was
      segregated from the gene(s) involved in tumor progression during selection and
      inbreeding of the SENCAR mouse stock.

PMID- 1375871
TI  - Rat macrophage activation after treatment with the bleomycin group of antitumour
      antibiotics in vivo.
AB  - We have previously reported that bleomycin and its derivative peplomycin enhance
      the release of cytokines by rat spleen cells during mitogen-stimulated cell
      culture in vitro, but liblomycin, another derivative of bleomycin, decreases
      cytokine release to below untreated control levels. Cytokine release correlated
      well with the inhibition of subcutaneous tumour growth after treatment with
      equivalent doses of the three analogues. In contrast, ascites tumour growth is
      completely inhibited by liblomycin and appears to be at least partly macrophage
      mediated because the antitumour effect can be significantly inhibited by
      carageenan. This study shows that bleomycin and its analogues activate rat
      peritoneal macrophages and increase interleukin-6 release, O2- production, cell
      spreading, phagocytosis and random migration of macrophages, but only bleomycin
      enhances peritoneal macrophage invasion into a monolayer of rat lung endothelial
      cells in vitro. This study also shows that although liblomycin decreases spleen
      cell cytokine production and is less effective than bleomycin against
      subcutaneous tumour, as we have previously reported, the antitumour drug
      activates peritoneal macrophages and, compared to bleomycin, has a remarkable
      therapeutic effect on rat ascites tumour.

PMID- 1375874
TI  - Mercurochrome interference with the Abbott TDx.

PMID- 1375872
TI  - Influence of antibody protein dose on therapeutic efficacy of radioiodinated
      antibodies in nude mice bearing GW-39 human tumor.
AB  - The biodistributions of three 131I-labeled murine monoclonal antibodies, NP-4 and
      Immu-14 anti(carcinoembryonic antigen), and Mu-9 anti-(colon-specific antigen p),
      were determined at antibody protein doses varying from 1 microgram to 1000
      micrograms in nude mice with small (0.1-0.4 g) GW-39 human colonic cancer
      xenografts. For each antibody, the percentage of the injected dose per gram of
      tumor and tumor/nontumor ratios were constant over a wide protein dose range.
      However, at high protein doses (above 100 micrograms for NP-4 and Immu-14) the
      percentage of the injected dose per gram of tumor and tumor/nontumor ratios
      decreased. Assuming that the uptake of a control anti-(alpha-fetoprotein)
      antibody represents the amount of antibody that accumulates in the tumor
      nonspecifically (i.e., antigen-independently), it could be shown that for each
      antibody the amount of antibody protein that accumulates in the tumor
      specifically, increases linearly with the protein dose, reaching a plateau level
      at the highest doses tested. The growth inhibition of GW-39 tumor transplants in
      nude mice treated with 131I-labeled antibody at either low or high antibody
      protein dose was compared. These experiments indicated that, in this experimental
      model, enhanced antibody protein dose may decrease the therapeutic efficacy of
      radioiodinated antibodies. It is suggested that heterogeneous distribution at low
      protein dose, with intense localization around the blood vessels, may enhance the
      tumoricidal effect of radioantibodies.

PMID- 1375875
TI  - Age-related changes of neuron-specific enolase, S-100 protein, and myelin basic
      protein concentrations in cerebrospinal fluid.
AB  - Studies on cerebrospinal fluid (CSF) concentrations of neuron-specific enolase
      (NSE), S-100 protein, and myelin basic protein (MBP) in patients with
      neurological lesions indicate a quantitative relation between the degree of cell
      damage in the central nervous system (CNS) and the concentration of these CNS
      specific proteins in CSF. Thus NSE, S-100, and MBP could be of use as markers for
      destructive processes in the CNS. We collected 937 specimens of CSF from children
      and adults (from newborns to age 91 years) who were undergoing a diagnostic
      lumbar puncture for several clinical indications. Of these, 79 samples from
      subjects ranging in age from 0.7 to 66 years could be used retrospectively to
      construct a reference interval according to our criteria. In these 79 samples no
      sex dependency existed. The relative increase of NSE, S-100, and MBP with age was
      similar (1% per year), suggesting a common underlying mechanism. These results
      emphasize the necessity of using age-matched reference values when the CNS
      specific proteins are to be evaluated in neurological diseases. We also present
      three case histories to discuss the possible clinical relevance of the
      measurement of NSE, S-100, and MBP in children and adults.

PMID- 1375873
TI  - Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid
      cancer by a local immunotherapy.
AB  - To elucidate the mechanism of action for intratumoral injection of
      immunopotentiators, infiltrating mononuclear cells and tumor necrosis factor
      (TNF) were assayed by immunostaining tissue samples of differentiated thyroid
      cancer resected with or without presurgical local application of OK-432, a
      streptococcal preparation. Frozen sections of resected specimens were stained
      with monoclonal antibodies using either a conventional or a modified
      immunoperoxidase method. The tumors injected with OK-432 showed increased T
      lymphocyte infiltration and HLA-DR expression on cancer cells as compared to the
      non-injected controls. Among these T cells, the CD4+ subset was more numerous
      than the CD8+ population. In four out of the seven cases constituting the
      injected group, numerous TNF-positive cells were seen in clusters or lines as
      well as scattered, while none of the seven cases in the control group was
      associated with a considerable amount of these cells. In their morphology and
      distribution pattern, these TNF-positive cells appeared to be of macrophage
      lineage. Thus local injection of OK-432 in thyroid cancer was shown to recruit T
      lymphocytes of predominantly the CD4+ subset and to induce in situ production of
      TNF, a known potent tumoricidal cytokine. The present data warrant further
      studies in this direction besides wider clinical intratumoral application of the
      reagent.

PMID- 1375877
TI  - Immunoassays for quantifying choriogonadotropin compared for assay performance
      and clinical application.
AB  - We examined calibration and accuracy, precision, sensitivity, specificity, and
      "hook" effects for recently revised automated choriogonadotropin (hCG)
      immunoassay systems (Baxter-Dade Stratus II, Abbott IMx intact hCG and total beta
      hCG) and compared them with a widely used immunoradiometric assay (Hybritech). We
      estimated hCG in pregnant women, women with trophoblastic disease, nonpregnant
      young and menopausal women, normal men, and men with testicular tumors. We found
      clinically unimportant differences in calibration (all calibrated to the 3rd
      International Standard). Detection of hCG by all four assays was limited by their
      responses in serum from nonpregnant women and men. Precision within-run was best
      for the automated instruments, but all four assays had similar between-run
      precision. The Hybritech, Stratus, and IMx intact assays are specific for intact
      hCG. The IMx total beta assay quantifies both free beta subunit and beta subunit
      present in intact hCG. There is a clinically important hook effect in the
      Hybritech assay but not the Stratus or IMx assays (to 1.2 x 10(6) int. units/L).
      Results for pregnant women were similar by all four assays. We measured "hCG" to
      8 int. units/L in menopausal women, which weakly correlated with concentrations
      of lutropin and follitropin and was, in part, explained by crossreactivity. There
      was no sample-probe carryover in either instrument. We found the IMx diluting
      module as well as results at the extremes of the IMx calibration curves (less
      than 10, 800-1200 int. units/L) unreliable but encountered no such problems with
      the Stratus system. Both automated systems involve batch analyzers with limited
      throughput but provide hCG concentration estimates much more quickly than the
      Hybritech assay can.

PMID- 1375876
TI  - Two-site monoclonal antibody-based immunoradiometric assay for measuring prostate
      secretory protein in serum.
AB  - We developed a double-determinant immunoradiometric assay for measuring serum
      prostate secretory protein (PSP), using monoclonal antibodies (MAb) against two
      different epitopes: MAb PSP-19 was the capture antibody and MAb PSP-6 was the
      tracer antibody. Assay sensitivity was 0.1 microgram/L. Analytical recovery of
      PSP was 93.5-104.6%, whereas the intra- and interassay mean CVs were 4.2% and
      6.9%, respectively. In 92 normal men, ages greater than 50 years, the mean PSP
      concentration was 5.7 micrograms/L, with 10 (10.9%) men having concentrations
      greater than 10 micrograms/L. In contrast, 20 of 49 (40.8%) patients with benign
      prostate hyperplasia (BPH; mean PSP concentration 9.4 micrograms/L) and 46 of 100
      (46%) patients with prostate cancer (mean PSP concentration 22.2 micrograms/L)
      had PSP concentrations greater than 10 micrograms/L. Mean serum PSP
      concentrations of the BPH (P less than 0.05) and prostate cancer (P less than
      0.01) groups were significantly different from those of age-matched normal men.
      In a small group of patients, serial PSP concentrations correlated with the
      clinical course during therapy. Thus, PSP may be a useful marker for evaluating
      patients with prostate cancer.

PMID- 1375878
TI  - [The epaulette flap: replantation of osteomyocutaneous forearm segments in
      interscapulo-thoracic amputation].
AB  - Despite sophisticated artificial limb devices available today, forequarter
      amputation following trauma or tumor resection will lead to severe impairment of
      function. To close the posttraumatic or oncologically required extended defects
      and to improve prosthetic supplementation coverage of the thoracic wall should be
      performed by sparing the whole forearm as an osteomyocutaneous flap. In cases of
      concomitant serial rib resection radius and ulna will serve as stabilizators of
      the thoracic wall, thus avoiding a flail chest. Indications, technical details
      and clinical outcome of three salvage replantations after interscapulo-thoracic
      ablation will be discussed.

PMID- 1375879
TI  - A short latency cortical component of the foveal VEP is revealed by hemifield
      stimulation.
AB  - Transient evoked potentials were recorded simultaneously over 5 electrodes placed
      in a horizontal row across the occiput. A range of spatial frequencies were
      presented as either full-field or hemifield stimuli. Subjects were 11 normal
      observers and 5 patients with lesions causing a homonymous hemianopic field
      defect. The shortest latency peak response was at approximately 70 msec, a
      negative potential (N70). For all spatial frequencies, full-field stimuli evoked
      a lower amplitude N70 at the midline than the sum of N70 amplitudes to two
      hemifield stimuli, suggesting partial cancellation. The latency and amplitude of
      N70 increased as spatial frequency increased. N70 and P100 differed in respect to
      their response to spatial frequency and field size, further suggesting that they
      may not be subsets of a unitary response. For hemifield stimulation, N70 had an
      ipsilateral maximum and attenuated or completely reversed in polarity across the
      midline. Consistent with the data of normals using hemifield stimuli, in 5
      patients a full-field stimulus elicited an N70 lateralized contralaterally to the
      homonymous hemianopia, i.e., the ipsilateral N70 was absent. The absolute
      amplitude difference between the left and right electrodes was significant for
      hemifield stimulation in normals and full-field stimulation in the patients, but
      not for full-field stimulation in normals. Our results imply that the evaluation
      of N70 hemispheric distribution is useful for the evaluation of paramacular
      visual field defects.

PMID- 1375880
TI  - A VEP study of the visual pathway function in compressive lesions of the optic
      chiasm. Full-field versus half-field stimulation.
AB  - Changes of the pattern reversal visual evoked potentials (VEPs) to half- and full
      field stimulation in 50 patients with compressive lesions of the optic chiasm are
      presented. Temporal half-field stimulation yielded abnormal responses in 85% of
      the eyes, showing non-recordable P100 in 50% of eyes, while in 35% the P100 was
      significantly attenuated or delayed. With nasal half-field the percentage of all
      detectable abnormalities was lower (36% of the eyes). Full-field stimulation
      revealed VEP abnormalities in 74% of eyes and therefore proved less sensitive
      than the half-field stimulation. This study adds new evidence that half-field
      stimulation can be an important adjunct for assessing the function of the optic
      chiasm.

PMID- 1375881
TI  - Subcortical contributions to the surface-recorded flash-VEP in the awake macaque.
AB  - Epidural mapping of flash-VEP in awake monkeys revealed a reliable, short latency
      negativity, N25 (onset: 18-22 msec; peak: 23-27 msec; duration: 15-20 msec), with
      a broad frontal surface distribution (frontolateral maximum). N25 was dissociable
      from the electroretinogram (ERG), from cortical VEP and from the high frequency
      oscillations (wavelets) coextensive with the ERG and with cortical VEP. Depth
      recordings traced N25 from its surface maximum down to the lateral geniculate
      nucleus (LGN). Concomitant VEP, current source density (CSD) and multiunit
      activity (MUA) profiles obtained with multicontact electrodes showed that the
      peak and later portion of N25 arise primarily from current sinks (associated with
      MUA increases) that reflect transmembrane current flow attending depolarization
      of cells in lamina 6, the uppermost lamina, but may also receive contributions
      from the more ventral LGN laminae. The initial portion of N25 arises from similar
      processes near the lamina 3/2 border. Wavelets, in contrast, are prominent in
      VEP, CSD and MUA within LGN, but attenuate rapidly above LGN. LGN laminar and
      cellular morphology predict volume conduction of N25 over a wide arc lateral and
      anterior to LGN and roughly horizontal isopotential planes medial and posterior
      to LGN. Recordings on the brain surface, within LGN, and in the regions
      surrounding LGN are consistent with these predictions. Possible contributions
      from other structures and how these results fit with data obtained in humans are
      considered.

PMID- 1375882
TI  - Amplitude abnormalities in the scalp far-field N18 of SSEPs to median nerve
      stimulation in patients with midbrain-pontine lesion.
AB  - Various amplitude ratios were measured in 20 normal controls and 36 patients with
      midbrain-pontine, thalamic or putaminal lesions in order to evaluate the
      amplitude abnormalities in scalp far-field N18 following median nerve
      stimulation. A study of normal controls showed that the distributions of P9/N18,
      P14/N18 and N18/P14 + N18 resembled a gaussian distribution and could be used as
      criteria for determining the decrease in N18 amplitude in each patient. There was
      a decrease in N18 amplitude, or the absence of N18, in patients with midbrain
      pontine lesions, but not in those with thalamic or putaminal lesions. Nine
      amplitude ratios (P11/P9, P14/P9, N18/P9, P9/P11, P9/P14, P9/N18, N18/P14,
      P14/N18 and N18/P14 + N18) were compared statistically for normal controls and 3
      groups of patients based on non-parametric, Wilcoxon's non-pairs and signed-rank
      tests. A decrease in N18 amplitude in midbrain-pontine lesion was shown by
      significant changes in N18/P9, P9/N18, N18/P14, P14/N18 and N18/P14 + N18, no
      amplitude decreases in P11 and P14 being found from the amplitude ratios of
      P11/P9, P9/P11, P14/P9 and P9/P14. No significant changes were seen in any of the
      9 amplitude ratios when the normal controls and patients with thalamic and
      putaminal lesions were compared. The amplitude ratios of N18 can be used to
      detect a decrease in N18 amplitude in patients with midbrain-pontine lesions. The
      data obtained support the hypothesis that N18 originates in the midbrain-pontine
      region and that neither the thalamus nor thalamocortical radiation make major
      contributions to the formation of the N18 peak.

PMID- 1375883
TI  - The N30 component of somatosensory evoked potentials in patients with dystonia.
AB  - We recorded short-latency median nerve somatosensory evoked potentials (SEPs) in
      10 patients with dystonia (6 with focal dystonia, 3 with generalized dystonia,
      and 1 with segmental dystonia) and compared them with those of 10 normal
      controls. The EEG was recorded from 29 sites on the scalp with linked earlobe
      electrodes for reference. Latencies and amplitudes of P15, postcentral N20 and
      P45, and frontal N30 were evaluated. The latencies of all potentials were the
      same in patients and controls. The amplitudes of P15, N20 and P45 were also the
      same in both groups, but the N30 amplitude of the patients was larger than of the
      controls. The amplitude of N30 did not vary from the affected side to the
      unaffected side. Previous work has shown decreased N30 amplitude in patients with
      Parkinson's disease. Changes in N30 amplitude may be indicative of abnormal
      excitatory effects on cortex resulting from disorders of the basal ganglia.

PMID- 1375884
TI  - Current source density mapping of somatosensory evoked responses following median
      and tibial nerve stimulation.
AB  - Potential recording of brain activities always encounters the problem resulting
      from the activation of reference electrodes. Current source density (CSD)
      computation does not take reference sites into account and consequently may
      better localize the generator sources. In the past, several attempts have been
      made to record CSDs of the somatosensory evoked responses (SERs) following median
      nerve stimulation. In order to compare the generating mechanisms of SERs
      following median nerve and tibial nerve stimulation, the scalp CSD distributions
      of the median nerve SER and the tibial nerve SER were compared in 5 normal
      subjects. In the median nerve SER, far-field potentials such as P14 and N16 were
      abolished in the CSD records. N20, P25 and N35 showed almost identical CSD
      distributions, albeit P25 had a reversed polarity. By contrast, the tibial nerve
      SER showed similar distributions for P40 and P60 CSDs, but N50 had a different
      distribution from the others. In the potential records, P40 and P60 were
      distributed predominantly ipsilateral to the stimulus (paradoxical
      lateralization), whereas the P40 and P60 CSDs formed a dipole localized over the
      contralateral foot somatosensory area. N50 disclosed the same tendency, although
      it had a slightly different CSD pattern from that of P40 and P60. These findings
      suggest that the median nerve and tibial nerve SER components are not necessarily
      comparable and that under certain circumstances CSDs are better indicators of
      local electrical events than the corresponding potentials.

PMID- 1375885
TI  - Steady-state vibration evoked potentials: descriptions of technique and
      characterization of responses.
AB  - Steady-state scalp evoked potentials were recorded in response to amplitude
      modulated vibration applied to the fingers and palmar surface of one hand. Evoked
      response dependence on the frequency of amplitude modulation in the 2-40 Hz range
      was studied in a group of normal young adult volunteers. Response amplitude was
      greatest at low amplitude modulation frequencies. The greatest signal to EEG
      noise ratios were found at modulation frequencies near 26 Hz. At modulation
      frequencies near 26 Hz the steady-state response latency was found to be 58 +/-
      14 msec. Inverse dipole modeling localized the steady-state evoked response
      generators in or near somatosensory cortex with the dipole moment orientation
      being predominantly in the anterior-posterior direction.

PMID- 1375886
TI  - Potentials evoked in human and monkey medial temporal lobe during auditory and
      visual oddball paradigms.
AB  - Event-related potentials (ERPs) were recorded from epileptic patients with
      electrodes chronically implanted in the medial temporal lobe (MTL) and other
      intracranial locations, and from monkeys with epidural, transcortical, and MTL
      electrodes. For both humans and monkeys, the eliciting events consisted of trains
      of auditory or visual stimuli in which a random 10-20% deviated in pitch or
      pattern from the remaining stimuli. The distribution of ERPs elicited by the rare
      (oddball) stimuli in both species was similar, consisting of a P3 recorded from
      the scalp or cortical surface and a slightly later, but temporally overlapping,
      focal negativity in the hippocampus and nearby MTL structures. The similarity
      between the patterns of ERPs in humans and monkeys establishes the feasibility of
      studying the electrogenesis of P3-like activity with detailed intracranial
      recordings in an animal model. The data also establish that the MTL ERPs in human
      patients represent a normal neurophysiological process unrelated to epilepsy.

PMID- 1375887
TI  - The effect of different high-pass filter settings on peak latencies in the event
      related potentials of schizophrenics, patients with Parkinson's disease and
      controls.
AB  - Eighteen schizophrenic patients, 16 patients with idiopathic Parkinson's disease,
      and the same numbers of age, sex and education matched controls were examined
      with oddball experiments for the generation of P3. Individual averages were high
      pass filtered at different cut-off frequencies with single-pole digital filters
      with equivalent analogue Butterworth filter profiles. The purpose of this
      procedure was to simulate analogue high-pass filters used in clinical studies
      from different centres and to examine their potential effect on group
      differences. Increasing high-pass filters resulted in a phase lead for all peaks
      examined (N1, P2, N2, P3). The only group differences were found for P3, which
      showed a greater phase lead in controls than in the patient groups, usually
      resulting in a more pronounced group difference. Similar wave forms and filter
      properties could be modelled by synthetic wave forms consisting of sine waves of
      different frequencies.

PMID- 1375888
TI  - Mental movement simulation affects the N30 frontal component of the somatosensory
      evoked potential.
AB  - It is known that somatosensory evoked potentials can be influenced by several
      centripetal and centrifugal factors which modify their amplitude. The present
      study shows for the first time that the frontal waves N30 and to a lesser extent
      N23 are specifically attenuated during mental movement simulation (MMS) activity.
      This gating phenomenon, tested on 16 normal subjects, occurred when repeated fast
      finger movements on the stimulated side are mentally simulated. In contrast, no
      significant modification appeared when the subject performed the MMS activity
      with the hand contralateral to that receiving electrical stimuli or when the
      subject performed a mental operation unrelated to the MMS. The MMS was shown by
      Roland et al. (1980) to increase the regional blood flow exclusively in the
      supplementary motor area (SMA). Our experimental data therefore indicate that the
      SMA could play an important role in the generation of the frontal N30.

PMID- 1375889
TI  - Brain-stem auditory evoked potentials in adults with Down's syndrome.
AB  - Brain-stem auditory evoked potentials (BAEPs) were examined in 37 adult patients
      with Down's syndrome and in 37 age-matched normal subjects. All absolute and
      interpeak latencies except for the interpeak latency IV-V were shorter in
      patients than in normal subjects. The amplitude of wave V and the amplitude ratio
      V/I were smaller in patients than in normal subjects. Short latencies in patients
      were considered to be due to the smaller size of the brain-stem or to faster
      conduction velocity. The prolonged interpeak latency IV-V and the smaller wave V
      may indicate physiological dysfunctions between the upper pons and the lower
      midbrain.

PMID- 1375890
TI  - Middle latency auditory evoked potentials improve the detection of abnormalities
      along auditory pathways in multiple sclerosis patients.
AB  - Brain-stem and middle latency auditory evoked potentials (BAEPs and MLAEPs) have
      been studied in 34 multiple sclerosis (MS) patients. We were able to detect a
      central nervous system auditory pathway involvement in 17 (50%) of the patients:
      38% by BAEPs alone (I-V inter-peak latency) and 47% by MLAEPs alone (Na and Pa
      peak latency). Five patients had abnormal MLAEPs with normal BAEPs whereas the
      opposite was detectable in only 1 patient. In addition, most MLAEP parameters in
      the MS group statistically differed from those obtained in the control group.
      Therefore, our results demonstrated that the auditory pathway impairment could
      frequently be located at a rostral level along the auditory radiation. In
      conclusion, even if only Na and Pa components were considered, MLAEPs succeeded
      in improving the sensitivity of the auditory evoked potential examination without
      increasing the false positive rate.

PMID- 1375891
TI  - The possible role of gliotoxin in health and disease.
AB  - Demonstration of the unique therapeutic properties of penicillin initiated an
      extensive investigation of other mould metabolites in the hope of finding other
      useful chemotherapeutic agents. While many hundreds of active substances were
      studied very few indeed satisfied the criteria necessary for clinical use. Among
      those whose toxicity ruled them out was gliotoxin. Recently, however a chance
      observation, in quite a different context, suggests that gliotoxin may prove
      valuable in human tissue transplantation.

PMID- 1375892
TI  - Sensory mechanisms on the molecular level.
AB  - As sensory perception is the channel by which we learn about the nature of the
      world around us it has been the subject of philosophical inquiry since classical
      antiquity. With the emergence of science in its modern sense in the 17th century,
      experimental investigation began to be possible but it was only with the
      relatively recent advent of molecular biology that sensory perception can be
      studied at its basic level.

PMID- 1375893
TI  - Creation of an autocrine model of insulin-like growth factor-I action in
      transfected FRTL-5 cells.
AB  - Although there is much evidence that insulin-like growth factor-I (IGF-I) is
      delivered to its target tissues via the circulation from distal sites of
      synthesis, many other observations suggest that it is synthesized in or near its
      target tissues and acts by autocrine and/or paracrine modalities. Studies of the
      mechanisms of such local actions, however, have been problematic, because in vivo
      studies of a single tissue are technically difficult and confounded by many
      variables, whereas in vitro studies of autocrine/paracrine actions have been
      limited by low levels of IGF-I expression and/or lack of dramatic or clearly
      defined responses to IGF-I. We, therefore, set about to create IGF-I expression
      in FRTL-5 cells, a diploid nontransformed line of rat thyroid follicular cells
      that have been extensively studied as a model of TSH action. The modest increase
      in thymidine incorporation stimulated by TSH in wild type FRTL-5 cells is
      markedly increased in the presence of exogenous IGF-I. By transfecting these
      cells with a chimeric IGF-IA gene, driven either by the mouse metallothionein-1
      or IGF-II 5' genomic regulatory regions, we were able to generate stable cell
      lines that synthesize and secrete mature IGF-I. This was demonstrated by RIA, by
      Northern analysis, and by polyacrylamide gel electrophoresis characterization of
      the radiolabeled intracellular and extracellular products that reacted with an
      IGF-I antibody. The mitogenic responses to TSH in IGF-I-expressing transfected
      FRTL-5 cells were indistinguishable from those stimulated by TSH and IGF-I in
      wild type or control-transfected cells (FRTL-5 cells stably transfected with a
      similar transgene that does not encode IGF-I). Basal DNA synthesis was higher and
      the peak of thymidine incorporation was earlier in IGF-I-expressing transfected
      FRTL-5 cells than in wild type or control cells (18-24 h vs. 30-36 h). The
      concentrations of TSH that maximally stimulate the incorporation of thymidine
      were not altered by IGF-I expression, and transfected cells did not appear to be
      transformed, as judged by their inability to form colonies in soft agar. TSH
      stimulated DNA synthesis was blocked in IGF-I-expressing FRTL-5 cell by a
      monoclonal antibody to IGF (Sm 1.2). Thus, secretion of IGF-I appears to be
      required for the autocrine effects observed. These IGF-I-expressing FRTL-5 cell
      lines provide a model in vitro system to study the intracellular processing of
      IGF-I and the mechanisms by which IGF-I acts in an autocrine manner.

PMID- 1375894
TI  - Effects of rat alpha-fetoprotein administration on estradiol free fraction, the
      onset of puberty, and neural and uterine nuclear estrogen receptors.
AB  - The cause of the onset of puberty in the rat or any other mammalian species is
      unknown. According to one theory, puberty is initiated through switching of the
      brain "gonadostat." It is hypothesized here that puberty in the rat is the
      consequence of the appearance of free, and therefore physiologically active,
      estrogen in the circulation. To test this, the unbound fraction of estradiol in
      serum of immature female rats was measured in relation to the nuclear receptor
      occupancy of estradiol in the hypothalamus, preoptic area, and uterus at various
      times after birth. In addition, an attempt was made to alter the free fraction of
      estradiol by injection of the estradiol-binding protein alpha-fetoprotein (AFP)
      into immature female rats. The free fraction of estradiol was low (less than 1%),
      but began rising at about 20 days of age, and a significant increase in nuclear
      bound estradiol was observed in 23-day-old rats (P less than 0.001). By day 30,
      unbound levels attained adult values (3.99 +/- 0.15%). At this time, nuclear
      bound estradiol in all tissues examined fell (P less than 0.01), but by day 40,
      these were greatly increased in rats in estrus (P less than 0.001), being trebled
      in the preoptic areas and doubled in the hypothalamus. Injection of AFP into
      immature female rats extended the period of low free estradiol (1.22 +/- 0.08%),
      while in albumin-injected rats, the free fraction was 4.44 +/- 0.1%. Injection of
      AFP resulted in levels of nuclear-bound estradiol that were less than half those
      measured in nuclei from AFP-injected animals (P less than 0.001), and AFP delayed
      puberty. The affinity of the reaction between estradiol and nuclear receptors in
      brains of immature and mature rats was not significantly different; the Kd fell
      within the range of 0.05-0.08 nM. It is suggested that in the rat, puberty is the
      result of the appearance in the circulation of physiologically active estradiol
      after day 20.

PMID- 1375895
TI  - Potentiation of insulin-like growth factor (IGF) action by IGF-binding protein-3:
      studies of underlying mechanism.
AB  - In this study we investigated the mechanism(s) by which insulin-like growth
      factor-binding protein-3 (IGFBP-3) potentiates IGF-I action in cultured bovine
      fibroblasts. Preincubation of cells with glycosylated or nonglycosylated
      recombinant human IGFBP-3 enhanced responsiveness to IGF-I in a time-dependent
      manner. A preincubation period of at least 24 h with IGFBP-3 was required to see
      a significant effect. Pretreatment with IGFBP-3 for 72 h resulted in a 2- to 4
      fold augmentation of IGF-I-stimulated [3H]aminoisobutyric acid uptake; IGFBP-3
      had no effect on basal [3H]aminoisobutyric acid uptake. During the preincubation
      period, exogenous IGFBP-3 associated with the fibroblast surface and exhibited
      time-dependent processing to lower mol wt forms that retained the ability to bind
      radiolabeled IGF-I. Initial surface adherence (preincubation time of 24 h or
      less) was readily reversible. However, IGFBP-3, once processed, appeared to be
      closely associated with the cell. After 72 h of exposure to bovine fibroblasts,
      cell-associated IGFBP-3 had a 10-fold lower affinity for IGF-I compared to intact
      IGFBP-3 in solution. In addition, incubation of bovine fibroblasts with IGFBP-3
      had modifying effects on type I IGF receptor-mediated signalling because 1) the
      bioeffectiveness of [Gln3,Ala4,Tyr15,Leu16]IGF-I and insulin, IGF-I receptor
      activators with little or no affinity for IGFBP-3, was potentiated by
      preincubation with IGFBP-3; and 2) fibroblast responsiveness to IGF-I analogs
      with different affinities for the type I IGF receptor was enhanced in direct
      relation to the ability of the peptide to bind to the receptor. There was no
      evidence for an increase in receptor number or affinity as a result of IGFBP-3
      treatment. These data suggest that IGFBP-3 potentiation of IGF-I action in bovine
      fibroblasts may involve changes in IGFBP-3 and type I IGF receptor
      responsiveness. Thus, cell-associated IGFBP-3 may provide a mechanism for optimal
      presentation of IGF-I to its receptor as well as a means to heighten receptor
      reactivity to IGF-I and related peptides.

PMID- 1375896
TI  - Progesterone inhibits the estrogen-induced expression of c-fos messenger
      ribonucleic acid in the uterus.
AB  - Estradiol produces a large increase in the uterine level of c-fos mRNA, which is
      maximum in 3 h. The administration of progesterone antagonizes this estrogen
      induced increase in protooncogene transcript levels in both the rat and mouse.
      The inhibitory effect of progesterone is observed within 1 h after hormone
      treatment and persists for 9-18 h. In the rat, this effect can be observed at a
      dose of 0.25 mg progesterone and is maximum at a dose of 2.5 mg. A similar
      inhibition of fos mRNA levels after estrogen administration is produced by the
      glucocorticoid dexamethasone, but not by androgens or mineralocorticoids.
      Progesterone does not block the induction of c-jun or c-myc mRNA by estradiol.
      Uterine levels of c-fos mRNA observed after treatment with the phorbol ester
      phorbol 12-myristate 13-acetate are not decreased by a 3-h pretreatment with
      progesterone. Under the conditions of our experiments, progesterone does not
      decrease occupied levels of nuclear estrogen receptors in the uterus after
      estradiol administration. These findings are consistent with a mechanism in which
      progesterone inhibits transcriptional activation by the estrogen receptor at the
      level of the c-fos gene.

PMID- 1375897
TI  - Anatomical relationships in the patterns of insulin-like growth factor (IGF)-I,
      IGF binding protein-1, and IGF-I receptor gene expression in the rat kidney.
AB  - The rat kidney is both a target of circulating insulin-like growth factor-I (IGF
      I) and a site of local IGF-I production. In order to identify which renal
      structures produce IGF-I and the functionally related IGF binding protein 1
      (IGFBP-1), and which structures are potential sites of circulating or endogenous
      renal IGF action, we have employed in situ hybridization to localize IGF-I, IGFBP
      1, and IGF-I receptor messenger RNAs (mRNAs) in the rat kidney. The effects of
      hypophysectomy (Hx) and GH replacement on renal IGF-I, IGFBP-1, and IGF-I
      receptor gene expression have also been evaluated. IGF-I and IGFBP-1 mRNAs are
      both localized in the epithelial cells of medullary thick ascending limbs (TALs)
      of Henle's loops in the normal rat kidney. IGF-I receptor mRNA is also abundant
      in TALs, but, in addition, is distributed throughout the distal nephron and
      collecting duct, and in the glomerulus, with lowest levels found in proximal
      tubules. Hx and GH treatment had complex effects on patterns of renal IGF-I and
      IGFBP-1 gene expression. In general, Hx resulted in decreased IGF-I and increased
      IGFBP-1 mRNA levels, and GH treatment produced the opposite effects, while IGF-I
      receptor mRNA levels were not significantly effected by either treatment.
      However, the most dramatic effect produced by the interruption of the pituitary
      renal axis was the demonstration of reciprocal changes in IGF-I vs. IGFBP-1 gene
      expression in individual kidneys and even in individual nephrons, suggesting a
      local interaction between IGF-I and IGFBP-1 in the regulation of their respective
      mRNA levels. Functional implications issuing from these anatomical relationships
      in renal patterns of IGF-I, IGFBP-1, and IGF-I receptor gene expression are that
      IGF-I, if secreted into the tubular lumen, possibly carried or modulated by IGFBP
      1, may act on luminal TAL and downstream receptor sites. The specific
      physiological role of IGF-I produced in TALs is open to speculation. Glomerular
      IGF-I receptor sites, based on their localization upstream and distant from local
      sources of IGF-I production, are predicted to be targets for circulating IGFs.

PMID- 1375898
TI  - Differential regulation by growth hormone (GH) of insulin-like growth factor I
      and GH receptor/binding protein gene expression in rat liver.
AB  - We have reported that female hypophysectomized (hypox) rats replaced with T4 and
      cortisone and treated for 7 days with GH injections (4 x 12.5 micrograms/day) had
      significantly greater growth and increase in serum insulin-like growth factor-I
      (IGF-I) than did hypox rats continuously infused with GH (50 and 250
      micrograms/day), whereas GH binding to liver membranes was increased only by
      infusion. We now report the effects of hypophysectomy, T4 and cortisone
      replacement, and the aforementioned continuous vs. intermittent GH treatment on
      liver IGF-I and GH receptor (GHR)/binding protein (GHBP) gene expression in
      female rats. Concentrations of IGF-I peptide were measured in acid-extracted sera
      and liver tissues. Total GH binding to liver membranes was determined in MgCl2
      treated homogenates and serum GH binding activity was assessed by gel filtration
      of serum incubated with 125I-bovine GH. The abundance of messenger RNA (mRNA)
      transcripts encoding IGF-I, the GHR, and the GHBP was quantified by Northern
      hybridization analysis of liver poly(A)+ RNA. Hypophysectomy in female animals
      decreased serum IGF-I and liver IGF-I mRNA concentrations by 95% and 87%,
      respectively, serum GHBP activity, and total liver GH binding by 50% (P less than
      0.001 compared with intact controls), and liver GHR and GHBP mRNA abundance by 30
      35% (P less than 0.05 vs. controls). These changes were not reversed by T4 and
      cortisone treatment. Repeated injections of GH produced a 13-fold increase in
      liver IGF-I peptide and a 5-fold increase in liver IGF-I mRNA concentrations (vs.
      saline-treated hypox rats), whereas continuous GH infusions induced only 7-fold
      and 2-fold increases in IGF-I peptide and mRNA, respectively. Serum GHBP activity
      was not changed in the GH-injected animals, but rose 2- to 3-fold in the GH
      infused rats, an increase similar to that reported for their liver GH binding
      sites. No major change in liver concentrations of GHR and GHBP mRNAs was seen
      after repeated GH injections. Differential regulation of the two GHR/GHBP gene
      products was observed after continuous infusion of GH, with a net 60-70% increase
      in liver GHBP mRNA abundance contrasting with no apparent change in the GHR mRNA
      transcript. These results indicate that pulsatile GH administration is more
      effective than continuous GH infusion in stimulating liver IGF-I gene expression,
      and this effect is not mediated by an increase in GHR mRNA or protein.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1375899
TI  - Steroids and tissue-specific modulation of galanin gene expression in the male
      rat reproductive system.
AB  - Galanin is a neuropeptide widely distributed throughout the vertebrate neural and
      endocrine system. Galanin can influence pituitary hormone secretion, intestinal
      motility, and other biological activities. The precise physiological role of
      galanin is unknown. We studied the control of galanin gene expression in
      peripheral organs in the male rat using Northern blot and in situ hybridization
      techniques. In the adrenals and prostate, galanin mRNA was undetectable in the
      controls and did not change after the administration of dexamethasone (0.0001
      10.0 mg/kg, ip) and diethylstilbestrol (0.1 mg/kg, ip). In the testis, thymus,
      seminal vesicles, medial basal hypothalamus, and colon, galanin message was
      detectable, but was not influenced by steroids. On the other hand, dexamethasone
      (0.5-10.0 mg/kg) was very effective in enhancing galanin expression in the vas
      deferens and epididymis (4- to 7-fold in the vas deferens), with a peak 6-9 h
      after the treatment. Diethylstilbestrol (0.1 mg/kg) stimulated galanin mRNA
      transcription only in the vas deferens (2- to 3-fold), with a peak 1-3 h after
      the treatment. Dihydrotestosterone treatment (0.2-0.4 mg/kg) was ineffective in
      all tissues examined. In the vas deferens and seminal vesicles, galanin mRNA has
      been localized at a cellular level by in situ hybridization. In these tissues
      only fibroblast-like cells contained the message. These data demonstrate that
      galanin is expressed in the male rat reproductive system and that steroid
      hormones participate in the control of galanin gene expression in a tissue- and
      hormone-specific fashion.

PMID- 1375900
TI  - Steroidal regulation of hypothalamic neuropeptide Y release and gene expression.
AB  - Neuropeptide Y (NPY) readily stimulates the release of hypothalamic LHRH and
      pituitary LH release in intact and gonadal steroid-primed gonadectomized rats. We
      have now tested the hypothesis that the release and synthesis of hypothalamic NPY
      may be regulated by gonadal steroids. To measure the effects of gonadal hormones
      on NPY release, a permanent push-pull cannula was implanted in the anterior
      pituitary (AP) of sham castrated (controls) or castrated (CAST) male rats, and 1
      week later, the AP was perfused with artificial cerebrospinal fluid over a 3-4 h
      period. NPY concentrations in the perfusates collected at 10-min intervals were
      measured by RIAs. The NPY release pattern in the AP was episodic in both intact
      and CAST rats, and the frequency of NPY episodes was similar in two groups.
      However, the amount of NPY detected in the AP of CAST rats was significantly less
      than that of intact rats because the mean rate of release and the amplitude of
      NPY episodes in the perfusates of CAST rats were significantly reduced. This
      observation of attenuated hypothalamic NPY output in vivo and previous evidence
      of decreased hypothalamic NPY contents after CAST implied that the synthesis of
      hypothalamic NPY may be regulated by testicular secretions. Therefore, the
      effects of testosterone (T)-replacement on preproNPY messenger RNA (mRNA) in the
      medial basal hypothalamus (MBH) was evaluated. Rats were CAST and received either
      empty or T-filled Silastic capsules sc. Two weeks later, the level of perproNPY
      mRNA in the MBH was determined by solution hybridization/ribonuclease protection
      assay using a complementary RNA probe complementary to the rat NPY precursor
      mRNA. We observed that the levels of preproNPY mRNA were 2-fold higher in the MBH
      of T-replaced CAST as compared to control CAST rats. These findings are
      consistent with the hypothesis that gonadal steroids enhance the neurosecretory
      activity of hypothalamic NPYergic neurons, and for the first time reveal a
      coupling between the level of gene expression and the secretion of a neuropeptide
      involved in the regulation of hypothalamic LHRH and pituitary LH release.

PMID- 1375901
TI  - Protein phosphatase inhibitors and bone resorption: inhibition by okadaic acid
      and biphasic actions of calyculin-A.
AB  - PTH receptors on osteoblasts and calcitonin receptors on osteoclasts are coupled
      to adenylate cyclase. Despite similar transduction mechanisms, these hormones
      have opposing physiological actions. We investigated the consequences of
      persistent protein phosphorylation on bone resorption in neonatal mouse calvariae
      using okadaic acid (OA) and calyculin-A, two inhibitors of protein phosphatase-1
      and -2A. These two inhibitors caused different responses in bone at picomolar and
      low nanomolar concentrations. OA inhibited, in a dose-dependent manner, bone
      resorption stimulated by PTH, 1,25-Dihydroxyvitamin D3, phorbol ester, and
      prostaglandin E2 (PGE2). OA did not inhibit the generation of the second
      messengers cAMP or PGs and did not have nonspecific toxic effects, as measured by
      protein and RNA synthesis. Thus, OA appeared to mimic the global inhibitory
      action of calcitonin on bone resorption. Unlike OA, calyculin-A elicited a
      biphasic dose response. At concentrations of 3.3 nM and greater, calyculin-A
      inhibited, in a dose-dependent manner, stimulated bone resorption. However,
      calyculin-A alone, at 0.625 and 2.5 nM, stimulated bone resorption via a PG
      independent pathway. In calvariae, OA and calyculin-A increased phosphorylation
      of a 58- to 60-kilodalton protein. A protein of similar molecular mass was
      hyperphosphorylated in OA-treated ROS 17/2.8 osteoblast-like cells. We conclude
      that in addition to hormonal regulation of protein kinase activity, protein
      dephosphorylation plays a functionally important role in the modulation of bone
      resorption.

PMID- 1375902
TI  - Induction of avidin messenger ribonucleic acid in the chick oviduct by
      progesterone and other steroids.
AB  - Avidin gene expression was analyzed using an avidin immunoassay and RNA
      hybridization analysis. To ascertain whether the induction of the avidin gene by
      progesterone remains specific also during secondary restimulation with
      diethylstilbestrol, chicks were given different steroid hormones or hormone
      combinations. Progesterone-specific induction of avidin protein and messenger RNA
      (mRNA) was 15- to 30-fold over the control even after secondary restimulation
      with diethylstilbestrol. A functional difference between the progesterone
      response element and glucocorticoid response element was suggested, since
      dexamethasone alone did not induce avidin in vivo. In spite of progesterone
      specificity, a combination of progesterone with other steroids nevertheless
      generated a synergistic increase in the amount of avidin mRNA. This may indicate
      that binding of progesterone receptor to the progesterone response element may be
      important to alter the functional activity of other hormone response elements
      present on the avidin gene. The time response curve of the avidin mRNA induction
      by progesterone was also determined. Avidin mRNA was detectable 8 h after
      progesterone induction, and its amount was maximal after 16-24 h. This would
      indicate that the avidin gene belongs in the so-called late responder genes,
      which also include chicken ovalbumin, ovomucoid, and lysozyme genes.

PMID- 1375903
TI  - Expression of transforming growth factor-beta isoforms (beta 2 and beta 3) in the
      mouse uterus: analysis of the periimplantation period and effects of ovarian
      steroids.
AB  - Expression of beta-type transforming growth factor genes (TGF beta 2 and TGF beta
      3) in the mouse uterus during the periimplantation period and in response to an
      acute exposure to 17 beta-estradiol (E2) and progesterone (P4) was studied using
      Northern blot hybridization and/or immunocytochemistry. Polyclonal antipeptide
      antibodies specific for TGF beta 2 or TGF beta 3 were employed for
      immunocytochemistry. In the preimplantation uterus [days (D) 1-4 of pregnancy;
      day 1 = vaginal plug], immunostaining for TGF beta 2 was observed in luminal and
      glandular epithelia as well as in myometrium and vascular smooth muscle. In the
      postimplantation period (D5-D8), TGF beta 2 immunostaining was also detected in
      decidual cells. In contrast, TGF beta 3 immunostaining was restricted to the
      myometrium and vascular smooth muscle throughout the periimplantation period (D1
      D8). Antisense TGF beta 2 and TGF beta 3 RNA probes were employed for Northern
      blotting. Northern blot hybridization revealed four TGF beta 2 transcripts
      (approximately 6.0, 5.0, 4.0, and 3.5 kilobases) in total uterine poly(A)+ RNA on
      D1-D6 and in poly(A)+ RNA from the deciduum and myometrium collected on D7 and D8
      of pregnancy. These TGF beta 2 transcripts were also detected in isolated samples
      of deciduomata or myometrium obtained from D8 pseudopregnant mice in which the
      decidual cell reaction was induced experimentally on D4. The levels of these
      transcripts remained relatively constant during the periimplantation period.
      Northern blot analysis detected a 3.8-kilobase TGF beta 3 transcript in total
      uterine poly(A)+ RNA on D1-D6. This transcript was detected in myometrial RNA
      samples on D7 and D8 of pregnancy or D8 of pseudopregnancy, but was not detected
      in RNA from the deciduum on D7 and D8 or in that from deciduomata on D8. The
      effects of ovarian steroids on TGF beta 2 and TGF beta 3 mRNAs were examined in
      uteri of adult ovariectomized mice. Uterine TGF beta 2 or TGF beta 3 mRNA
      persisted in ovariectomized mice. However, an injection of E2 induced a rapid (6
      h), but transient, induction (approximately 3- to 4-fold) of TGF beta 2 mRNA. An
      injection of P4 had no effect on TGF beta 2 mRNA levels, and coinjection of P4
      with E2 did not antagonize the E2-stimulated transient accumulation of TGF beta 2
      mRNA. In comparison, neither an injection of E2 nor one of P4 exerted significant
      effects on TGF beta 3 mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375904
TI  - Regulation of avian calbindin-D28K gene expression in primary chick kidney cells:
      importance of posttranscriptional mechanisms and calcium ion concentration.
AB  - Vitamin D-dependent calcium-binding protein (calbindin-D28K), is regulated by
      1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and several other factors in a tissue
      specific manner, but the controlling mechanisms are still poorly understood. In
      this study we examined the relative contributions of transcriptional and
      posttranscriptional mechanisms in the 1,25-(OH)2D3 control of calbindin-D28K mRNA
      expression in primary chick kidney cells and investigated the effect of
      extracellular Ca2+ on calbindin-D28K gene expression in the presence and absence
      of hormone. 1,25-(OH)2D3 treatment (10(-8) M) of cells grown in serum-free medium
      resulted in a marked 20- to 30-fold increase in calbindin-D28K mRNA peaking at 12
      18 h, which then rapidly declined to basal levels by 24 h. The abrupt decline in
      mRNA appeared to be associated with a reduction in size of the calbindin-D28K
      transcripts. Nuclear run-off assays showed only a slight (1.5-fold) increase in
      calbindin-D28K gene transcription 2 h after 1,25-(OH)2D3, whereas parallel assays
      clearly demonstrated a marked (7-fold) induction in the rate of metallothionein
      gene transcription 2 h after treatment of chick kidney cells with 10 microM zinc.
      The induction of calbindin-D mRNA by 1,25-(OH)2D3 required ongoing protein
      synthesis, since it was blocked by cycloheximide. Calbindin-D28K mRNA was stable
      for 12 h in the presence of actinomycin-D in both vitamin D-deficient and 1,25
      (OH)2D3-treated cells. Both basal and 1,25-(OH)2D3-induced calbindin-D28K mRNA
      were modulated by the extracellular Ca2+, with maximum expression occurring at 1
      2 mM. We conclude that 1,25-(OH)2D3 induces kidney calbindin-D28K mRNA by
      producing a small increase in its transcriptional rate, which is accompanied by
      pronounced posttranscriptional effects(s). The striking modulation of calbindin
      D28K expression by extracellular Ca2+ is consistent with a putative role for this
      protein in the regulation of this ion in the kidney cell.

PMID- 1375905
TI  - Production of mitogenic factor(s) by ovine corpora lutea throughout the estrous
      cycle.
AB  - To evaluate secretion of mitogenic factors by ovine corpora lutea (CL) at several
      stages of development, luteal explants from days 5 (n = 12 ewes), 10 (n = 6
      ewes), and 15 (n = 6 ewes) of the estrous cycle were incubated in serum-free
      medium for 24 h. Luteal-conditioned media (LCM) were evaluated for their ability
      to stimulate proliferation of endothelial, BALB/3T3, and ovarian granulosa cells.
      After mitogenic activity of LCM from individual animals was evaluated, pools of
      LCM from each day of the estrous cycle were subjected to anion-exchange, cation
      exchange, and heparin-affinity chromatography to characterize mitogenic activity.
      Pools of LCM also were utilized for ultrafiltration, heat-treatment, trypsin
      treatment, and immunoneutralization studies. Results demonstrated that ovine CL
      secrete mitogenic activity that stimulates (P less than 0.01) proliferation of
      endothelial (135.7 +/- 5.3% of control) and granulosa cells (188.9 +/- 2.9%) but
      not 3T3 (103.2 +/- 2.5%) cells. Differences between stages of luteal development
      were not observed. The mitogenic activity bound to diethylaminoethyl-Sephacel and
      heparin-agarose, but not to carboxymethyl-Sepharose, indicating that ovine luteal
      mitogenic factor(s) is anionic and may belong to the heparin-binding growth
      factor (HBGF) family. In addition, the mitogenic activity was heat-labile,
      trypsin-sensitive, and appeared to have a M(r) greater than 100,000. Mitogenic
      activity for endothelial cells was partially neutralized with a specific antibody
      against HBGF-1 and was completely abolished with a specific antibody against HBGF
      2. Moreover, HBGF-1 and HBGF-2 were immunolocalized in histological sections of
      CL from days 5 (n = 5 ewes), 10 (n = 5 ewes), and 15 (n = 5 ewes) after estrus.
      These findings are the first report of a major mitogenic factor(s) produced by
      cyclic ovine CL and indicate this factor is an HBGF-2-like molecule.

PMID- 1375906
TI  - Retinoic acid regulates insulin-like growth factor II expression in a
      neuroblastoma cell line.
AB  - Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides that
      play an important role in normal growth and development. IGF-II has been shown to
      stimulate the growth of neuroblastoma tumors in an autocrine and paracrine
      fashion. Critical in determining the role of IGF-II in tumorigenesis is the
      necessity to delineate factors affecting the transcription of IGF-II in normal
      and tumor tissues. To date such factors are poorly characterized. In this study
      we find that retinoic acid (RA), a naturally occurring morphogen, that has been
      shown to be indispensable in the development of the chick limb bud, stimulates an
      increase in IGF-II messenger RNA (mRNA) in the Lan-1-15N neuroblastoma cell line.
      This increase in IGF-II is coincident with RA mediated inhibition of DNA
      synthesis. An increase in the steady state levels of IGF-II mRNA is detectable
      within 2 h of RA treatment and maximal by 24 h. In RA-treated Lan-1-15N cells,
      IGF-II mRNA levels are regulated at the level of new gene transcription and
      result in an increase in IGF-II protein in the culture supernatant. These studies
      suggest one mechanism affecting the production of IGF-II in vivo may be mediated
      by RA and detail a model system by which transcriptional regulation of IGF-II
      mRNA can be analyzed.

PMID- 1375907
TI  - Follistatin steady state messenger ribonucleic acid levels in confluent cultures
      of a rat renal mesangial cell line are regulated by multiple factors.
AB  - The regulation of steady state levels of follistatin (FS) messenger RNA (mRNA)
      was examined in a rat renal mesangial cell line in tissue culture. A specific 32P
      radiolabeled antisense probe was used which corresponds to the 3' end of exon 5
      together with the 5' end of exon 6 of the rat FS gene, and which distinguishes
      between the two different forms of FS mRNA. In addition, a specific 35S
      radiolabeled probe for the ubiquitous protein cyclophilin was developed and used
      as an internal standard. Total RNA was harvested from confluent cell cultures to
      yield four independent samples per treatment/time point, and equal amounts of RNA
      from every sample in a given experiment were subjected to S1-nuclease analysis
      for the estimation of specific mRNA levels. Treatment of the cultured cells with
      epidermal growth factor (10 nM) caused an 8- to 9-fold increase in the FS mRNA
      level after 4 h, but no consistent change was observed after treatment with basic
      fibroblast growth factor (0.28 or 0.56 nM), somatostatin (3.7-73 nM), angiotensin
      II (0.1-2500 nM), or FS itself (0.29 nM) for between 4 and 48 h. Neither activin
      (0.5 or 1.2 nM) nor inhibin (0.64 nM) changed the FS mRNA level in the mesangial
      cell line during a 24-h treatment. FS mRNA levels in the cells also were not
      affected by a 48-h treatment with the steroids dihydrotestosterone (1-1000 nM),
      estradiol (1 and 100 nM), and the antiprogesterone RU 486 (1000 nM), whereas 100
      nM RU 28362 (a synthetic glucocorticoid) caused a 5- to 6-fold increase and 1000
      nM progesterone increased the FS mRNA level up to 3.5-fold above control.
      Retinoic acid, a vitamin A derivative, significantly increased the FS steady
      state mRNA level at 3 nM, and at 1000 nM stimulated FS mRNA up to 5-fold within 4
      h, whereas incubation of the cells with 30 microM prostaglandin E2 for 4 h caused
      a 10-fold increase. The FS mRNA level increased 3- and 4-fold within 4 h during
      incubation of the cells with 100 nM phorbol 12-myristate, 13-acetate, and 25
      microM forskolin, respectively, whereas the calcium ionophore A23187 (1-100
      microM) caused no change within this timespan. None of the tested hormones had an
      obvious effect on the ratio of the two different forms of FS mRNA (FS 344:FS
      317).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375909
TI  - Enhanced histamine release from lung mast cells of guinea pigs exposed to
      sulfuric acid aerosols.
AB  - To clarify the relationship between air pollution and mast cell response, the
      effects of sulfuric acid aerosols on histamine release from lung mast cells of
      guinea pigs were investigated. Guinea pigs were exposed to 0.3, 1.0 and 3.2 mg/m3
      sulfuric acid (H2SO4) aerosols or 4 ppm nitrogen dioxide (NO2) for 2 and 4 weeks.
      After the exposure, lung mast cell suspensions were isolated by collagenase
      treatment and antigen- or A23187-induced histamine release was measured. Antigen
      induced histamine release from mast cells was significantly enhanced by the
      exposure to 1.0 and 3.2 mg/m3 H2SO4 for 2 weeks, but exposure to H2SO4 for 4
      weeks did not show the enhancement of antigen-induced histamine release. A23187
      induced histamine release was significantly enhanced by the exposure to 1.0 mg/m3
      H2SO4 or 4 ppm NO2 for 2 weeks, but suppression of histamine release from lung
      mast cells stimulated with A23187 was observed by the exposure to 3.2 mg/m3 H2SO4
      for 4 weeks. The exposure to 0.3 mg/m3 H2SO4 showed no changes in antigen- and
      A23187-induced histamine release. The combination of 1.0 mg/m3 H2SO4 with 4 ppm
      NO2 for 2 weeks resulted in no changes in antigen- and A23187-induced histamine
      release. These results suggested that functional properties of lung mast cells
      may be altered by a low concentration of H2SO4 aerosol exposure.

PMID- 1375908
TI  - Purified human alpha fetoprotein inhibits growth factor-stimulated estradiol
      production by porcine granulosa cells in monolayer culture.
AB  - Purified alpha fetoprotein (AFP) synergizes with transforming growth factor alpha
      (TGF alpha) and insulin-like growth factor I (IGF-I) to enhance proliferation of
      porcine granulosa cells (pGC) in primary culture, suggesting a role for AFP in
      the modulation of growth factor-mediated cell growth. TGF alpha stimulates basal
      estrogen production by pGC and is in fact more potent than FSH in these cells. In
      this study, we investigated the effects of AFP on growth factor-stimulated
      estradiol (E2) production by pGC. Basal production of E2 was not altered by the
      addition of AFP. AFP dose-dependently inhibited TGF alpha-stimulated E2
      production with statistically significant inhibition observed with 2.5
      micrograms/ml. We have previously shown that the mitogenic effects of AFP are
      maximized with TGF alpha+IGF-I. E2 production was even more sensitive to AFP
      inhibition when the two growth factors were combined. Human serum albumin (HSA;
      10 micrograms/ml) was without effect. AFP did not interfere with the E2 RIA,
      affect the uptake of or display specific in vitro binding of the androgen
      substrate. Furthermore, human AFP and HSA did not exhibit specific in vitro
      binding of E2, in contrast to purified rat AFP (positive control). These data
      indicate that physiological concentrations of purified AFP significantly and dose
      dependently inhibit growth factor-stimulated E2 production by pGC in culture.
      Since AFP is known to increase TGF alpha+IGF-I mediated cell growth, these data
      suggest that AFP may be inhibiting the differentiated function (steroidogenesis)
      of pGC while enhancing the proliferation of these cells.

PMID- 1375910
TI  - Small RNA helices as substrates for aminoacylation and their relationship to
      charging of transfer RNAs.
AB  - RNA microhelices that reconstruct the acceptor stems of transfer RNAs can be
      aminoacylated. The anticodon-independent aminoacylation is sequence-specific and
      suggests a relationship between amino acids and nucleotide sequences which is
      different from that of the classical genetic code. The specific aminoacylation of
      RNA microhelices also suggests a highly differentiated adaptation of the
      structures of aminoacyl-tRNA synthetases to sequences in the acceptor stems of
      transfer RNAs.

PMID- 1375911
TI  - Effects of angiotensins on cellular hypertrophy and c-fos expression in cultured
      arterial smooth muscle cells.
AB  - An increase in cell size and protein content was observed when quiescent arterial
      smooth muscle cells in culture were incubated with either angiotensin II or III.
      These effects were inhibited by the specific angiotensin type-1 receptor
      antagonist losartan (DuP753) but not by CGP42112A. In parallel, a transient and
      dose-dependent induction of c-fos was demonstrated not only with angiotensins II
      and III but also with angiotensin I. Both angiotensins II and III exerted their
      maximal effect at 1 microM, while angiotensin I needed a tenfold-higher
      concentration to exert an identical effect. As for hypertrophy, losartan also
      inhibits angiotensin-induced c-fos expression, suggesting that this gene may be
      involved into the hypertrophic process. Angiotensin-I-mediated c-fos induction is
      partially inhibited by the angiotensin-converting enzyme inhibitors captopril and
      trandolaprilate; given that an angiotensin-converting enzyme activity was
      detected in these smooth muscle cell cultures, these results suggest that
      angiotensin-I-induced c-fos expression is mediated in part via angiotensin-I
      conversion to angiotensin II, but also by other unidentified pathway(s).
      Angiotensin I could essentially induce smooth muscle cell hypertrophy by indirect
      mechanisms, while angiotensins II and III act directly on smooth muscle cells.

PMID- 1375912
TI  - Attenuation in the rph-pyrE operon of Escherichia coli and processing of the
      dicistronic mRNA.
AB  - We have substituted on a plasmid the native promoter of the Escherichia coli rph
      pyrE operon with an inducible transcription-initiation signal. The plasmid was
      used to study the mRNA chains derived from the operon at different intracellular
      concentrations of UTP and as a function of time following induction of
      transcription. The results showed that dicistronic rph-pyrE mRNA was formed when
      the UTP pool was low, and that a monocistronic rph mRNa was the major
      transcription product in high-UTP pools, thus supporting an UTP-controlled
      attenuation mechanism for regulation of pyrE gene expression. However, the
      dicistronic rph-pyrE transcript was rapidly processed into two monocistronic mRNA
      units, and a cleavage site was mapped near the attenuator in the intercistronic
      region, close to the site where transcription was terminated in high-UTP pools.
      Furthermore, the major 3' end of the pyrE mRNA was mapped near a palindromic
      structure of similarity to the family of repetitive extragenic palindromic
      sequences, 35 nucleotide residues after stop codon of the pryE gene.

PMID- 1375913
TI  - Determination of the nucleotide sequences in mouse U14 small nuclear RNA and 18S
      ribosomal RNA responsible for in vitro intermolecular base-pairing.
AB  - U14 small nuclear RNA (snRNA) is an evolutionarily conserved RNA species that
      plays a role in rRNA processing. The conserved ability of fungal, amphibian and
      mammalian U14 snRNAs to hybridize with both homologous and heterologous
      eukaryotic 18S rRNAs indicates a potential role for this intermolecular RNA/RNA
      interaction in U14 snRNA function. To understand better the possible role of this
      intermolecular base-pairing in rRNA processing, we have defined those nucleotide
      sequences in mouse U14 snRNA and 18S rRNA responsible for the observed in vitro
      hybridization. We have constructed, using synthetic DNA oligonucleotides, a U14
      snRNA gene which has been positioned behind a T7 RNA polymerase promoter site and
      then inserted into a plasmid. The presence of natural or engineered restriction
      endonuclease sites within this construct has permitted the in vitro transcription
      of full-length mouse U14 snRNA transcripts (an 87-nucleotide mouse U14 snRNA
      minus 5' or 3' leader sequences) or 3' terminally truncated U14 snRNA fragments.
      Hybridization of full-length or truncated fragments of U14 snRNA to mouse 18S
      rRNA demonstrated the utilization of a previously proposed 18S rRNA complementary
      sequence located near the 3' end of mouse U14 snRNA (nucleotides 65-78) for
      intermolecular hybridization. Conversely, RNase-T1-generated fragments of 18S
      rRNA capable of hybrid-selection by U14 snRNA have been isolated and sequenced. A
      nested set of hybrid-selected 18S rRNA fragments define a mouse 18S rRNA sequence
      (nucleotides 459-472) which exhibits perfect complementarity to the defined U14
      snRNA sequence 65-78. Primer-extension/chain-termination mapping of mouse U14
      snRNA.18S-rRNA hybrids has confirmed the formation of the proposed hybrid
      structure. A second set of observed complementary sequences in mouse U14 snRNA
      (nucleotides 25-38) and mouse 18S rRNA (nucleotides 82-95) are not used for the
      in vitro hybridization of these two RNAs. Presumably the involvement of this
      second 18S-rRNA-complementary sequence in the secondary/tertiary folding of mouse
      U14 snRNA prevents its base-pairing with 18S rRNA. However, the strong
      evolutionary conservation of both U14-snRNA.18S-rRNA hybrid structures and their
      juxtapositioning within the folded secondary structure of 18S rRNAs argues for a
      biological role for each in U14 snRNA function.

PMID- 1375914
TI  - Murine endothelial leukocyte-adhesion molecule 1 is a close structural and
      functional homologue of the human protein.
AB  - Human endothelial leukocyte-adhesion molecule 1 (ELAM-1), a cell-surface
      glycoprotein expressed solely on cytokine-activated endothelial cells, mediates
      the adhesion of blood neutrophils, memory T-cells and some monocytes. ELAM-1,
      also known as E-selectin or leukocyte endothelial-cell-adhesion molecule 2, is a
      member of the lectin/epidermal-growth-factor/complement-regulatory-protein-like
      cell-adhesion molecule family, which includes structurally related molecules
      referred to as selectins. They are all involved in cell/cell adhesion, playing
      roles in leukocyte trafficking which are currently only partially defined. We
      report here the isolation and characterization of the murine equivalent of human
      ELAM-1. Murine ELAM-1 is encoded by a single-copy gene, spanning about 13 kb,
      which is structurally organized into 14 exons and 13 introns; very similar to
      that of its human counterpart. The exon/intron architecture exactly parallels the
      domain structure of the encoded protein. A murine ELAM-1-specific cDNA was cloned
      from heart tissue of an interleukin-1-(IL-1)-treated mouse. Its nucleotide
      sequence shows an overall similarity of 70% to human ELAM-1 cDNA. Transiently
      expressed in Cos cells, the encoded protein promotes the adhesion between
      recombinant cells and both human polymorphic nuclear cells, as well as HL60 cells
      expressing S-Lewis-x sugar moiety. Northern blot studies revealed by far the
      highest expression of the murine ELAM-1 gene in heart tissue and only low
      expression in lung tissue of IL-1-treated mice. Within the promoter, most of the
      recently identified regulatory elements are conserved. An exception is the
      nuclear factor (NF) kappa B box sequence, which, in the murine ELAM-1 promoter,
      does not correspond to the consensus NF kappa B sequence (Lenardo and Baltimore,
      1989). Band-shift analyses show no binding to NF kappa B-like proteins. However,
      fusion of the murine ELAM-1 promoter to a chloramphenicol acetyltransferase
      reporter confers cytokine-inducible transcription, although at a lower level,
      when compared to the human ELAM-1 promoter. Our results demonstrate the existence
      of a murine homologue of the human gene and demonstrate for adhesion functional
      equivalence between the homologous proteins from the two species. In addition, we
      provide the first evidence of the utility of the murine model in addressing
      biological questions about the role which ELAM-1 plays in inflammation.

PMID- 1375915
TI  - The closely related homomeric and heterodimeric mannose-binding lectins from
      garlic are encoded by one-domain and two-domain lectin genes, respectively.
AB  - Lectin cDNA clones for two different lectins from garlic (Allium sativum L.)
      bulbs, ASAI and ASAII (ASA, Allium sativum agglutinin), were isolated and
      characterized. The first lectin, ASAI, is a heterodimer composed of two different
      subunits of 11.5 kDa and 12.5 kDa. It is translated from an mRNA of 1400
      nucleotides encoding a polypeptide of 306 amino acids with two very similar
      domains. N-terminal sequencing of the two polypeptides of the mature lectin
      confirmed that both subunits are derived from the same precursor and that each
      corresponds to one of the two domains in the sequence. In contrast to ASAI, the
      second garlic lectin, ASAII, is a homodimer of two identical 12-kDa subunits. It
      is translated from an mRNA of approximately 800 nucleotides encoding a
      polypeptide of 154 amino acids. Interestingly, the coding region of the ASAII
      cDNA clones is almost identical to that of the second domain of the ASAI cDNA
      clones.

PMID- 1375916
TI  - Formation of heterodimers of human-immunodeficiency-virus-type-1 reverse
      transcriptase by recombination of separately purified subunits.
AB  - Human-immunodeficiency-virus-type-1 reverse transcriptase exists in virions as a
      heterodimer of a M(r) 66,000 subunit and its C-terminally truncated form of M(r)
      51,000, but, when expressed as a recombinant M(r) 66,000 protein, a mixture of
      heterodimers and homodimers results which co-purify by most conventional
      techniques. We describe a method of hydrophobic chromatography which gives
      baseline separation of these two forms of the protein. This method has been
      applied to purify heterodimers formed by recombination of separately expressed
      and purified M(r) 66,000 and 51,000 subunits, resulting in significantly more
      homogeneous heterodimer preparations. The recombined heterodimer showed similar
      kinetic properties and RNase H activity to the standard heterodimer and a
      specific activity significantly higher than the original homodimer of the M(r)
      66,000 protein. Heterodimers having greater asymmetry have also been prepared by
      recombining Mr 66,000 subunits containing single-point or deletion mutations,
      with wild-type M(r) 51,000 subunits, and the resulting heterodimers analysed.

PMID- 1375917
TI  - Monoclonal antibodies against Pseudomonas aeruginosa elastase: a neutralizing
      antibody which recognizes a conformational epitope related to an active site of
      elastase.
AB  - We have established seven murine hybridoma cell lines which produce monoclonal
      antibodies (mAbs) against Pseudomonas aeruginosa elastase. The seven mAbs
      recognized at least six different epitopes on the elastase molecule. All mAbs
      inhibited both enzymatic activities of elastase and protease, in which elastin
      fluorescein and hide powder azure were used as substrates, respectively. One of
      them, mAb E-4D3, strongly neutralized enzymatic activities of peptidase in which
      furylacryloyl-glycyl-leucinamide was used as a substrate, as well as of elastase
      and protease. In contrast, the other six mAbs did not neutralize peptidase
      activity at all. The Ki value for furylacryloyl-glycl-leucinamide of E-4D3, as
      well as its Fab fragment, was comparable to those for metalloprotease inhibitors
      such as phosphoramidon and Zincov inhibitor. The binding of mAb E-4D3 was
      inhibited by phosphoramidon and Zincov inhibitor, but not by metal chelators such
      as EDTA and o-phenanthroline. A line of evidence suggests that mAb E-4D3 directly
      interacts with active site and highly neutralizes enzymatic activity of P.
      aeruginosa elastase. Data of Western blotting and ELISA suggest that mAb E-4D3 is
      likely to recognize an elastase molecule in a conformation-dependent manner as an
      epitope. In contrast, the neutralizing activity of the other mAbs against
      elastase and protease seems to be caused by a low accessibility of an enzyme to
      insoluble and high-molecular-mass substrates through the binding and steric
      hindrance of the mAbs to an enzyme.

PMID- 1375918
TI  - Fusion-inhibiting monoclonal antibodies and their relevant antigens in relation
      to sexual process of Dictyostelium discoideum.
AB  - Sexual cell fusion occurs between NC4 and HM1, the heterothallic strains in
      Dictyostelium discoideum. Cells of these strains are fusion incompetent when
      cultured on agar plates in the light and become fusion competent upon cultivation
      in a liquid medium in darkness. Two cell-surface components, gp70 and gp138, have
      been identified and characterized as being relevant to sexual cell fusion. Both
      are glycoproteins, and the former is detected only in fusion-competent HM1 cells,
      while the latter is detected both in fusion-competent HM1 and fusion-competent
      NC4 cells. We therefore suspect gp 70 to be responsible for cell recognition and
      gp138, for membrane fusion. Therefore, NC4 cells are expected to possess specific
      surface molecule(s) that can be recognized by HM1 cells. In the present study, we
      raised monoclonal antibodies (mAbs) against membrane fractions of NC4 cells and
      selected fusion-inhibiting mAbs to identify novel molecules related to sexual
      cell fusion in D. discoideum. Out of the five mAbs we obtained three, DE1, GG6,
      and HH9, were characterized. DE1 recognized antigens that specifically existed in
      fusion-competent NC4 cells but not in fusion-incompetent NC4 or HM1 cells. GG6
      recognized cell-surface proteins with approximate molecular weights of 125 and 32
      kDa in both fusion-competent NC4 and fusion-competent HM1 cells. In addition GG6
      also recognised other proteins commonly present in fusion-incompetent cells. The
      125 kDa protein appeared to be the same as gp138. The epitope recognized by HH9
      was sodium dodecyl sulfate (SDS)-sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1375919
TI  - Hormonal regulation of adult type keratin gene expression in larval epidermal
      cells of the frog Xenopus laevis.
AB  - Triiodothyronin (T3) is known to induce amphibian metamorphosis but other
      hormones such as glucocorticoids accelerate T3 action. The increase in plasma
      concentration of both T3 and glucocorticoids during metamorphic climax is
      correlated with the transformation of the epidermis from larval type
      (uncornified) to adult type (cornified). Previously we have shown that T3 induced
      adult-type 63 Kd keratin gene expression and cornification of the larval
      epidermis. In this study, we have examined the effects of T3 and hydrocortisone
      (HC) on the conversion of larval to adult epidermal cells in vitro. When larval
      epidermal cells were treated with both T3 and HC, they had a synergistic effect
      on adult-type keratin synthesis (both 63 Kd and 49 Kd keratins) and epidermal
      cornification. The synergistic effect between T3 and HC required a pretreatment
      with T3 for 3 days. During this time, addition of HC to cultures containing T3
      did not change the amount of 63 Kd keratin mRNA. Thus, HC did not reduce the lag
      time for epidermal cells to respond to T3. After 4 days of hormone treatment, T3
      increased the amount of 63 Kd keratin mRNA 9-fold while T3 and HC induced it 18
      fold. When cultures were pretreated with T3 for 3 days, a 1 day treatment with HC
      was sufficient to obtain the synergistic effect. Thus the induction of 63 Kd
      keratin gene expression by T3 required a much longer lag (3 days) than the lag
      required for the synergistic action of T3 and HC (less than 1 day).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1375920
TI  - Methylene chloride--an inhalation study to investigate pathological and
      biochemical events occurring in the lungs of mice over an exposure period of 90
      days.
AB  - Male B6C3F1 mice were exposed to 4000 ppm methylene chloride (MC) for 6 hr/day, 5
      days/week for up to 13 weeks. Groups of mice were killed at intervals from Day 2
      to Week 13. Whole lungs were examined morphologically, immunocytochemically, and
      biochemically. Biochemical and morphological examination was also performed on
      isolated Clara cells. The major initial morphological effect seen in lungs was
      acute Clara cell damage after one exposure to MC. However, this damage appeared
      to resolve after five consecutive daily exposures to MC. After a 2-day interval
      the Clara cell lesion reappeared on subsequent reexposure to MC. However, the
      severity of the lesion decreased over the duration of the study. The appearance
      and disappearance of the lesion in the Clara cell correlated well with the
      activity of cytochrome P450 monooxygenase in the Clara cell as assessed
      immunocytochemically (cytochromes P450IIB 1 and 2) in the whole lung and
      biochemically in the freshly isolated Clara cell (determined by ethoxycoumarin O
      dealkylation and aldrin epoxidation). When there was a marked decrease in
      cytochrome P450 monooxygenase activity the lesion was not present. This suggested
      that with time the lung (Clara cell) has developed tolerance to MC possibly due
      to the inactivation of a cytochrome P450 isozyme. The glutathione S-transferase
      metabolism of MC by the lung cytosol remained virtually unaltered throughout the
      study. Events accompanying the discussed changes include (1) a significant
      increase in nonprotein sulfhydryl in the lungs of all exposed animals, (2)
      altered plating characteristics of the isolated Clara cells from exposed lungs
      after 24 hr in culture, and (3) an increase in the number of bronchiolar cells in
      the S-phase after the first exposure to MC. The study also demonstrates the
      advantages of target cell isolation and study over whole lung biochemical
      investigation alone.

PMID- 1375921
TI  - Application of molecular encapsulation for toxicology studies: comparative
      toxicity of p-Chloro-alpha, alpha, alpha-trifluorotoluene in alpha-cyclodextrin
      vehicle versus corn oil vehicle in male and female Fischer 344 rats and B6C3F1
      mice.
AB  - The application of alpha-cyclodextrin (alpha-CD) as an alternative vehicle for
      water insoluble and volatile chemicals was investigated in toxicity studies of p
      chloro-alpha, alpha, alpha-trifluorotoluene (CTFT). Groups of F344 rats and
      B6C3F1 mice of each sex were administered CTFT (97% pure) by gavage in either
      corn oil or alpha-CD aqueous formulations daily for 14 consecutive days. The dose
      levels used were 10 (mice only), 50, 400, and 1000 mg/kg for corn oil vehicle and
      10, 50, and 400 mg/kg (maximum achievable dose at gavage volume of 5 ml/kg) for
      alpha-CD vehicle. With both vehicles CTFT and alpha 2u-globulin were found to
      accumulate in the male rat kidney after 14 days of exposure and a dose-related
      toxic nephropathy was observed at dose of 50 mg/kg or higher. The hepatocellular
      hypertrophy and cytoplasmic vacuolation of the adrenal cortex which appeared in
      dosed male and female rats were also found to be independent of vehicle. Clinical
      pathology findings suggested a mild anemia and cholestasis in rats. With both
      vehicles no tissue bioaccumulation of CTFT was found in male or female mice.
      Vehicle-independent hepatocellular hypertrophy and cholestasis were also observed
      in mice at doses of 400 and 1000 mg/kg. In conclusion, the alpha-CD vehicle does
      not affect the toxic responses of CTFT in both sexes of both species. The results
      of the studies suggest that alpha-CD may be an appropriate alternative vehicle
      for toxicity studies.

PMID- 1375922
TI  - [Treatment of tubal pregnancy with prostaglandins].

PMID- 1375923
TI  - Localization of the cytoadhesin integrins in the human cornea. An
      immunohistochemical study using monoclonal antibodies.
AB  - Cell-matrix interactions play a fundamental role in normal and pathological
      conditions. They can be mediated by the cytoadhesin subgroup of the integrin
      superfamily of adhesion molecules. Its members include the vitronectin receptor
      (VNR) and the platelet glycoprotein IIb/IIIa (GP IIb/IIIa). Both receptors are
      composed of an alpha-chain (alpha v and alpha IIb, respectively) coupled to a
      beta 3-chain. Using in situ immunohistochemistry and monoclonal antibodies, the
      authors studied the distribution of GP IIIa (common beta 3-chain), GP IIb/IIIa
      (alpha IIb-chain) and VNR (alpha v-chain) in normal and pathological corneal
      tissues. In the normal cornea, the limbal vascular endothelium was weakly alpha v
      positive. Occasionally, faint and granular staining was seen in the epithelium.
      In the pathological samples, an upregulated expression of the alpha v-chain was
      noticed on the corneal epithelium as well as on fibroblasts and corneal
      endothelium. The alpha IIb and beta 3-chains were consistently absent. These data
      suggest that expression of the VNR-alpha v-chain in the human cornea is modulated
      by soluble factors released during inflammation and wound healing. Dissociation
      of expression of the alpha v and beta 3-chains suggests usage of an alternative
      beta-chain by the VNR-alpha v-chain.

PMID- 1375924
TI  - Expansion, selection and mutation of antigen-specific B cells in germinal
      centers.

PMID- 1375925
TI  - Pulmonary function status of shopkeepers of Ahmedabad exposed to autoexhaust
      pollutants.
AB  - The study deals with evaluation of pulmonary function status (VC, FEV1% and FEF25
      75%) in Ahmedabad shopkeepers stationed near different traffic junctions and
      relating them with the levels of oxides of nitrogen (NOx) near these junctions
      categorised as Heavy, Medium and Low polluted area junctions. The pulmonary
      function test (PFT) values of heavy polluted and medium polluted area shopkeepers
      is compared with low polluted area shopkeepers. The influence of smoking habits
      and duration of exposure over PFT values was seen. The prevalence of airway
      obstruction in shopkeepers was compared with USA population. The results
      indicated significant impairment in FEV1% and FEF25-75% value in high polluted
      area shopkeepers where NOx level is much higher than TLV value. In medium
      polluted area, where NOx level is slightly higher than TLV value, shopkeepers
      demonstrated significant impairment in FEF25-75%. Smoking is found to have an
      additive effect. A linear increase in the prevalence of pulmonary impairment with
      increasing duration of exposure was evidenced. Shopkeepers exhibited higher
      prevalence of impairment in both smokers and non-smokers than USA population
      attributing it to the effect of autoexhaust pollutants. This study also denoted
      that FEF25-75% is an early indicator of obstruction in smaller airways which is
      the primary site of deposition of inhaled pollutants.

PMID- 1375926
TI  - Effects of the new 5-lipoxygenase inhibitor E6080 on leukotriene release in
      vitro.
AB  - Fundamental studies were conducted to examine the release of histamine and
      leukotriene (LT) C4 from lung fragments of guinea pigs and the effects of E6080
      on the release of LTB4 and LTC4 from lung fragments or inflammatory cells. The
      release of histamine and LTs showed large interindividual variations and a marked
      dependence on experimental conditions. Addition of 10 mM L-cysteine significantly
      increased LTC4 release compared with that in its absence (about 1.7 times, in
      terms of mean value). E6080 inhibited antigen-stimulated LTB4 and LTC4 release
      from passively sensitized human (IC50: LTB4 0.08 microM, LTC4 0.2 microM) and
      guinea-pig lung fragments (IC50: LTC4 1.1 microM). The LTB4 and LTC4 releases
      from healthy human polymorphonuclear leukocytes (calcium ionophore A23187) and
      from allergic patients' leukocytes (basophils, antigen) were inhibited by E6080
      with IC50 values of below 1.0 microM. Furthermore, the LTC4 release from rat
      alveolar macrophages (silica particles) was inhibited by E6080 with an IC50 of
      0.2 microM. The potent inhibition by E6080 might be a result of the inhibition of
      5-lipoxygenase, since 5-lipoxygenase in rat basophilic leukemia cell was
      inhibited by E6080 with an IC50 of 0.2 microM. The results confirm the potent
      inhibitory effects of E6080 on the release of LTs.

PMID- 1375927
TI  - Hemopoietic growth factors regulate the survival of human basophils in vitro.
AB  - Human basophils were purified from normal peripheral blood, using density
      gradient followed by negative panning selection. We tested the effects of
      hemopoietic growth factors on the survival of these basophils in vitro. In the
      absence of exogenous factors, basophils (purity greater than 90%) decreased in
      number rapidly. At day 7 only 11% of the cells remained alive in cultures; less
      than 1% of cells survived at day 14. Interleukin (IL)-3 maintained numbers of
      viable cells; cell viability was 67% at day 7 and 45% at day 14. Granulocyte
      macrophage (GM)-colony-stimulating factor (CSF) exhibited slight effect on the
      survival; 33% of cells remained at day 7. Other growth factors including
      granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no significant effect on
      the survival of basophils at all. Morphological and functional characterization
      of cells maintained by IL-3 revealed that they belonged to the basophil lineage.
      These observations indicate that normal basophils possess functional receptors
      for IL-3 and GM-CSF and that both factors modulate immediate- and delayed-type
      hypersensitivity reactions by prolonging the life span of basophils.

PMID- 1375928
TI  - Characterization of four in vitro established canine mammary carcinoma and one
      atypical benign mixed tumor cell lines.
AB  - Five spontaneous canine mammary tumors were cultured in vitro and cell lines were
      established. The tumors included three frozen carcinomas, fine-needle aspirate
      from one fresh carcinoma, and one fresh atypical benign mixed tumor. The cell
      lines have so far been cultured for about 2 yr and passaged between 45 and 200
      times. The cell lines expressed different types of intermediate filaments,
      including a heterogenous pattern. In some cases no intermediate filaments were
      expressed. Ultrastructure studies showed epithelial cells and cells intermediate
      between epithelial and myoepithelial types. Retrovirus associated A-particles
      were found in two carcinomas. The mixed mammary tumor cell line formed ductlike
      structures in collagen substrate. The cell lines grew when inoculated s.c. into
      male nude mice. Two carcinomas caused lymph node metastases in two mice and
      another carcinoma single lung metastases in one tested mouse. DNA hypodiploidy,
      studied by flow cytometry, in one of the primary carcinoma was retained in vitro,
      and this cell line showed polyploidy during later passages. The other cell lines
      had a more unstable DNA profile, although a tendency for polyploidy was found.
      These findings were also illustrated in chromosome studies.

PMID- 1375929
TI  - Biochemical and antigenic properties of the Campylobacter flagellar hook protein.
AB  - The flagellar filament-hook complex was removed from Campylobacter cells by
      shearing and was purified by differential solubilization and ultracentrifugation
      at pH 11 followed by cesium chloride buoyant density ultracentrifugation.
      Flagellar filaments were then dissociated in 0.2 M glycine-HCl (pH 2.2), and
      purified hooks were collected by ultracentrifugation. The hooks (105 by 24 nm)
      each displayed a conical protrusion at the proximal end, a concave cavity at the
      distal end, and helically arranged subunits. The apparent subunit molecular
      weight of the hook protein of seven of the eight Campylobacter strains studied
      was 92,500, while that of the other was 94,000. N-terminal amino acid analysis of
      the hook protein of two strains of Campylobacter coli and one strain of
      Campylobacter jejuni demonstrated that the first 15 residues were identical.
      Amino acid composition analysis showed that the Campylobacter hook protein
      contained 35.7% hydrophobic and 9.5% basic residues. Isoelectric focusing
      determined that the hook protein was acidic, with a pI of 4.9. Comparisons with
      the Salmonella and Caulobacter hook protein compositions and N-terminal amino
      acid sequences indicated that the Campylobacter protein was related, but more
      distantly than these two proteins were to each other. Immunochemical analysis
      with four different antisera and a panel of eight strains showed that
      serospecific epitopes were immunodominant. The Campylobacter hook proteins
      carried both cross-reactive and specific non-surface-exposed epitopes, as well as
      serospecific epitopes which were exposed on the surface of the assembled hook.
      One class of these surface-exposed hook epitopes was shared with serospecific
      flagellin epitopes and may involve posttranslational modification, while the
      second class of epitopes was hook specific and not shared with flagellin.

PMID- 1375931
TI  - Angiogenesis.

PMID- 1375930
TI  - Antigenic sites on porin of Haemophilus influenzae type b: mapping with synthetic
      peptides and evaluation of structure predictions.
AB  - The major surface-located protein in the outer membrane of Haemophilus influenzae
      type b (Hib) is porin, molecular mass, 38 kDa, 341 amino acids. To define
      precisely the molecular reactivities of nine mouse monoclonal antibodies (MAbs)
      against Hib porin, overlapping hexapeptides corresponding to the entire sequence
      of porin were synthesized. The epitopes recognized by the MAbs were mapped by
      enzyme-linked immunosorbent assay to stretches of 6 to 11 amino acids. Antigenic
      sites between amino acids 112 and 126, 148 and 153, 162 and 172, and 318 and 325
      were identified. The antigenic sites between amino acids 162 and 172 and between
      amino acids 318 and 325 were determined by flow cytometry to be on the bacterial
      cell surface. Four MAbs, POR.2, POR.3, POR.4, and POR.5, that react with amino
      acids 162 to 172 were able to discriminate among porins from the three major
      outer membrane protein subtypes of Hib, i.e., 1H, 2L, and 6U. A model for the
      topological organization of Hib porin was created by calculating the
      hydrophobicity, amphiphilicity, and turn propensity in its amino acid sequence.
      Determination of the molecular reactivities of the anti-Hib porin MAbs provided
      substantive evidence for the orientation of selected regions of porin in the
      outer membrane of Hib.

PMID- 1375932
TI  - Molecular cloning of a 25-kDa high affinity rapamycin binding protein, FKBP25.
AB  - Two FK506 binding proteins of molecular mass 12 kDa (FKBP12) and 13 kDa (FKBP13)
      have been identified as common cellular receptors of the immunosuppressants FK506
      and rapamycin. Here we report the molecular cloning and overexpression of a 25
      kDa rapamycin and FK506 binding protein (termed FKBP25) with peptidylprolyl cis
      trans-isomerase (PPIase) activity. The amino acid sequence, predicted from the
      FKBP25 cDNA, shares identity with FKBP12 (44%) and FKBP13 (47%) in the C-terminal
      97 amino acids. Unlike either FKBP12 or FKBP13, the nucleotide sequence of FKBP25
      contains a number of putative nuclear localization sequences. The PPIase activity
      of recombinant FKBP25 was comparable with that of FKBP12. The PPIase activity of
      FKBP25 was far more sensitive to inhibition by rapamycin (IC50 = 50 nM) than
      FK506 (IC50 = 400 nM). PPIase activity of 100 nM FKBP25 was almost completely
      inhibited by 150 nM rapamycin while only 90% inhibition was achieved by 4 microM
      FK506. These data demonstrate that FKBP25 has a higher affinity for rapamycin
      than for FK506 and suggest that this cellular receptor may be an important target
      molecule for immunosuppression by rapamycin.

PMID- 1375933
TI  - Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent
      protein kinase, protein kinase C, and calcium/calmodulin protein kinase;
      identification of flavin and calmodulin binding sites.
AB  - Nitric oxide (NO) is an important molecular messenger accounting for endothelial
      derived relaxing activity in blood vessels, mediating cytotoxic actions of
      macrophages, and functioning as a neurotransmitter in the brain and periphery. NO
      synthase (NOS) from brain has been purified to homogeneity and molecularly
      cloned. We now report that NOS is stoichiometrically phosphorylated by cAMP
      dependent protein kinase, protein kinase C, and calcium/calmodulin-dependent
      protein kinase, with each kinase phosphorylating a different serine site on NOS.
      Activation of PKC in transfected cells reduces NOS enzyme activity by
      approximately 77% in intact cells and by 50% in protein homogenates from these
      cells. Utilizing fluorescence spectroscopy we find that purified monomer NOS
      contains 1 molar equivalent of both FMN and FAD. This stoichiometry is supported
      by enzymatic digestion of the flavins with phosphodiesterase, and titration of
      the FMN with a specific FMN binding protein. We demonstrate that purified NOS is
      labeled by a photoaffinity derivative of calmodulin. These recognition sites on
      NOS provide multiple means for regulation of NO levels and "cross-talk" between
      second messenger systems.

PMID- 1375934
TI  - EPR detection of heme and nonheme iron-containing protein nitrosylation by nitric
      oxide during rejection of rat heart allograft.
AB  - The paramagnetic molecule nitric oxide (NO), produced from L-arginine by a
      specific enzyme (NO synthase), has been shown to be involved in a surprising
      variety of mammalian cellular responses, including the regulation of T cell
      immunity to alloantigens in vitro. In cytotoxic activated macrophages, NO
      production results in a characteristic pattern of alteration of iron-containing
      enzyme function that is mimicked by exposure to NO. Electron paramagnetic
      resonance (EPR) studies have shown the formation of iron-nitrosyl species during
      macrophage activation and also during sepsis, indicating that alteration of iron
      containing protein function may be the result of the well-documented tendency of
      NO to bind to metal ions. We have recently shown that the NO synthesis induced
      during alloantigenic activation of rat splenocytes inhibits lymphocyte
      proliferation and cytotoxic T-lymphocyte generation. This report demonstrates
      that iron-nitrosyl EPR signals similar to those observed in macrophages and
      during sepsis are present in the blood and in the grafted tissue of rats during
      the rejection of allogeneic (but not syngeneic) heart grafts. These signals are
      found in the blood and at the site of allograft rejection, but are not found in
      other tissues (such as spleen and lung), and are obliterated by administration of
      the immunosuppressant FK506. These results directly demonstrate the formation of
      iron-nitrosyl complexes during vascularized allograft rejection and suggest that
      consequent destruction of iron-containing protein function plays an important
      role in the rejection response.

PMID- 1375935
TI  - The gene for stinging nettle lectin (Urtica dioica agglutinin) encodes both a
      lectin and a chitinase.
AB  - Chitin-binding proteins are present in a wide range of plant species, including
      both monocots and dicots, even though these plants contain no chitin. To
      investigate the relationship between in vitro antifungal and insecticidal
      activities of chitin-binding proteins and their unknown endogenous functions, the
      stinging nettle lectin (Urtica dioica agglutinin, UDA) cDNA was cloned using a
      synthetic gene as the probe. The nettle lectin cDNA clone contained an open
      reading frame encoding 374 amino acids. Analysis of the deduced amino acid
      sequence revealed a 21-amino acid putative signal sequence and the 86 amino acids
      encoding the two chitin-binding domains of nettle lectin. These domains were
      fused to a 19-amino acid "spacer" domain and a 244-amino acid carboxyl extension
      with partial identity to a chitinase catalytic domain. The authenticity of the
      cDNA clone was confirmed by deduced amino acid sequence identity with sequence
      data obtained from tryptic digests, RNA gel blot, and polymerase chain reaction
      analyses. RNA gel blot analysis also showed the nettle lectin message was present
      primarily in rhizomes and inflorescence (with immature seeds) but not in leaves
      or stems. Chitinase enzymatic activity was found when the chitinase-like domain
      alone or the chitinase-like domain with the chitin-binding domains were expressed
      in Escherichia coli. This is the first example of a chitin-binding protein with
      both a duplication of the 43-amino acid chitin-binding domain and a fusion of the
      chitin-binding domains to a structurally unrelated domain, the chitinase domain.

PMID- 1375936
TI  - P-selectin and E-selectin. Distinct but overlapping leukocyte ligand
      specificities.
AB  - P-selectin on platelets and endothelial cells and E-selectin on endothelial cells
      are leukocyte receptors that recognize lineage-specific carbohydrates on
      neutrophils and monocytes. The proposed ligands for these receptors contain the
      Le(x) core and sialic acid. Since other investigators have shown that both E
      selectin and P-selectin bind to sialylated Le(x), we evaluated whether E-selectin
      and P-selectin recognize the same counter-receptor on leukocytes. The interaction
      of HL60 cells with Chinese hamster ovary (CHO) cells expressing P-selectin or E
      selectin was studied. To determine whether a protein component is required in
      addition to sialyl Le(x) for either P-selectin or E-selectin recognition, HL60
      cells or neutrophils were digested with proteases, including chymotrypsin,
      elastase, proteinase Glu-C, ficin, papain, or thermolysin. Cells treated with
      these proteases bound E-selectin but not P-selectin. Fucosidase or neuraminidase
      treatment of HL60 cells markedly decreased binding to both E-selectin- and P
      selectin-expressing CHO cells. Growth of HL60 cells in tunicamycin inhibited the
      ability of these cells to support P-selectin-mediated binding and, to a lesser
      extent, E-selectin-mediated binding. Purified P-selectin inhibited CHO:P-selectin
      binding to HL60 cells, but incompletely inhibited CHO:E-selectin binding to HL60
      cells. However, purified soluble E-selectin inhibited CHO:P-selectin and CHO:E
      selectin binding to HL60 cells equivalently and completely. COS cells, unable to
      bind to E-selectin or P-selectin, bound E-selectin but not P-selectin upon
      transfection with alpha-1,3-fucosyltransferase or alpha-1,3/1,4
      fucosyltransferase. Similarly, LEC 11 cells expressing sialyl Le(x) bound E
      selectin- but not P-selectin-expressing CHO cells. Sambucus nigra lectin,
      specific for the sialyl-2,6 beta Gal/GalNAc linkage, inhibited P-selectin but not
      E-selectin binding to HL60 cells. Although sialic acid and Le(x) are components
      of the P-selectin ligand and the E-selectin ligand, these results indicate that
      the ligands are related, having overlapping specificities, but are structurally
      distinct. A protein component containing sialyl Le(x) in proximity to sialyl-2,6
      beta Gal structures on the P-selectin ligand may contribute to its specificity
      for P-selectin.

PMID- 1375937
TI  - CCK-JMV-180, an analog of cholecystokinin, releases intracellular calcium from an
      inositol trisphosphate-independent pool in rat pancreatic acini.
AB  - In pancreatic acinar cells cholecystokinin and its analogs, caerulein and CCK-JMV
      180, stimulate an increase in intracellular free [Ca2+] by releasing Ca2+ from
      non-mitochondrial intracellular pools. It is generally believed that the
      caerulein-induced release of Ca2+ is mediated by phospholipase C-catalyzed
      production of 1,4,5-inositol triphosphate (IP3). In this study we have
      investigated the source and mechanism of Ca2+ release induced by CCK-JMV-180
      using streptolysin O-permeabilized pancreatic acinar cells. Caerulein-stimulated
      release of Ca2+ was completely blocked by either neomycin, an inhibitor of
      phospholipase C, or by heparin, an IP3 receptor antagonist. These observations
      are compatible with the conclusion that caerulein releases Ca2+ from an IP3
      sensitive pool. In contrast to caerulein, however, CCK-JMV-180-stimulated release
      of Ca2+ was not blocked by either neomycin or by heparin, indicating that CCK-JMV
      180 releases Ca2+ by mechanisms which do not involve the generation or action of
      IP3. CCK-JMV-180 stimulated the release of Ca2+ even after the IP3-sensitive pool
      had been completely emptied by prior exposure to a supramaximally stimulating
      concentration of IP3 (40 microM). Prestimulation of permeabilized acini with 20
      mM caffeine did not abolish the CCK-JMV-180-induced Ca2+ release. These results
      indicate that CCK-JMV-180 stimulates release of Ca2+ from a hitherto
      uncharacterized intracellular storage pool which is insensitive to either IP3 or
      caffeine.

PMID- 1375938
TI  - The dephosphorylation of insulin and epidermal growth factor receptors. Role of
      endosome-associated phosphotyrosine phosphatase(s).
AB  - The autophosphorylation, from [gamma-32P]ATP, of insulin and epidermal growth
      factor receptors in rat liver endosomes peaked at 2-5 min and declined
      thereafter. When autophosphorylation from either [gamma-32P]ATP or unlabeled ATP
      was stopped after 5 min by adding excess EDTA +/- ATP, the phosphotyrosine (PY)
      content of each receptor decreased at 37 degrees C with a t 1/2 of 1.6 min. This
      was equally so whether the PY content of 32P-labeled receptors was analyzed by
      autoradiography of KOH-treated gels or by Western blotting with PY antibodies of
      immunoprecipitated receptors. The dephosphorylation reaction was strictly
      dependent on the presence of sulfhydryl, was unaffected by the addition of rat
      liver cytosol, and was temperature-dependent. The phosphotyrosine phosphatase(s)
      (PTPase(s)) appeared to be tightly anchored to the endosomal membrane, since the
      dephosphorylation reaction was unaffected by sodium carbonate and 0.6 M KCl
      treatments. However, treatment with Triton X-100 abolished dephosphorylation,
      implying an intimate association between the PTPase(s) and its substrate in an
      intact membrane environment. The powerful insulinomimetic agent pervanadate was
      the most potent inhibitor (50% inhibition at 1 microM). Increasing the dose of
      injected ligand augmented the rate of insulin and decreased that of EGF receptor
      dephosphorylation, respectively. Immunoblotting with specific antibodies failed
      to identify PTPase 1B or T-cell PTPase in ENs, whereas positive signals were seen
      in plasma membrane. These studies indicate that the phosphorylation state of
      receptor tyrosine kinases is dynamically regulated, with dephosphorylation, by
      closely associated PTPase(s), playing an important role.

PMID- 1375940
TI  - Ca2+/calmodulin-dependent cytochrome c reductase activity of brain nitric oxide
      synthase.
AB  - Nitric oxide acts as a widespread signal molecule and represents the endogenous
      activator of soluble guanylyl cyclase. In endothelial cells and brain tissue, NO
      is enzymatically formed from L-arginine by Ca2+/calmodulin-regulated NO synthases
      which require NADPH, tetrahydrobiopterin, and molecular oxygen as cofactors. Here
      we show that purified brain NO synthase binds to cytochrome c-agarose and
      exhibits superoxide dismutase-insensitive cytochrome c reductase activity with a
      Vmax of 10.2 mumol x mg-1 x min-1 and a Km of 34.1 microM. Cytochrome c reduction
      was largely dependent on Ca2+/calmodulin and cochromatographed with L-citrulline
      formation during gel filtration. When reconstituted with cytochrome P450, NO
      synthase induced a moderate Ca(2+)-independent hydroxylation of N-ethylmorphine.
      NO synthase also reduced the artificial electron acceptors nitro blue tetrazolium
      and 2,6-dichlorophenolindophenol. Cytochrome c, 2,6-dichlorophenolindophenol, and
      nitro blue tetrazolium inhibited NO synthase activity determined as formation of
      L-citrulline from 0.1 mM L-arginine in a concentration-dependent manner with half
      maximal effects at 166, 41, and 7.3 microM, respectively. These results suggest
      that NO synthase may participate in cellular electron transfer processes and that
      a variety of electron-acceptors may interfere with NO formation due to the broad
      substrate specificity of the reductase domain of NO synthase.

PMID- 1375939
TI  - Inactivation of human fibroblast growth factor-1 (FGF-1) activity by interaction
      with copper ions involves FGF-1 dimer formation induced by copper-catalyzed
      oxidation.
AB  - Although the angiogenic proteins acidic fibroblast growth factor (FGF-1) and
      basic fibroblast growth factor (FGF-2) both interact with the transition metal
      copper, itself a putative modulator of angiogenesis, a role for copper in FGF
      function has not been established. Using nonreducing sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, we detect the complete conversion of
      recombinant forms of human FGF-1 monomer protein to FGF-1 homodimers after
      exposure to copper ions. In contrast, not all forms of bovine FGF-1 isolated from
      bovine brain or a recombinant preparation of human FGF-2 completely formed
      homodimers after exposure to copper ions under similar conditions. Since the
      copper-induced FGF-1 homodimers reverted to the monomer form in the presence of
      dithiothreitol, specific alkylation of cysteine residues by pyridylethylation
      prevented FGF-1 homodimer formation, and preformed FGF-1 homodimers could not be
      dissociated by the metal chelator EDTA, FGF-1 dimer formation appeared to result
      from the formation of intermolecular disulfide bonds by copper-induced oxidation
      of sulfhydryl residues. FGF-1 homodimers bound with similar apparent affinity as
      FGF-1 monomers to immobilized copper ions, both eluting at 60 mM imidazole. Both
      human FGF-1 monomer and dimer forms had a 6-fold higher apparent affinity for
      immobilized copper ions, as compared with human FGF-2, which eluted in the
      monomer form at 10 mM imidazole. Further, in contrast to FGF-1 monomers, which
      dissociate from immobilized heparin in 1.0 M NaCl, preformed FGF-1 homodimers had
      reduced apparent affinity for immobilized heparin and eluted at 0.4 M NaCl. In
      contrast, the apparent affinity of human FGF-2 for immobilized heparin was
      unaffected after exposure to copper ions. Heparin appeared to modulate the
      formation of copper-induced intermolecular disulfide bonds for FGF-1 but not FGF
      2, since co-incubation of heparin and copper with FGF-1 monomers resulted in
      dimers and other oligomeric complexes. FGF-1 copper-induced homodimers failed to
      induce mitogenesis in [3H]thymidine incorporation assays, an effect which could
      be reversed by treatment with dithiothreitol, whereas FGF-2-induced mitogenic
      activity was relatively unaffected by pretreatment with copper. The differences
      between human FGF-1 and FGF-2 in protein-copper interactions may be due to
      differing free thiol content and arrangement between the two proteins. A
      recombinant human FGF-1 mutant containing the two cysteines conserved throughout
      the FGF family of proteins but lacking a cysteine residue (Cys 131) present in
      wild-type human FGF-1 but not human FGF-2 readily formed copper-induced
      dimers.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1375941
TI  - Isolation and characterization of alpha 2-macroglobulin-protease complexes from
      purified mouse mammary tumor virus and culture supernatants from virus-infected
      cell lines.
AB  - Cleavage of oligopeptide substrates mimicking the maturation sites in the Gag
      polyproteins of the mouse mammary tumor virus was assayed using lysed virus.
      Cleavage at the expected P1-P1' positions was detected in four of seven synthetic
      peptides. However, studies with specific inhibitors of retroviral proteases
      showed that only two of them could be unequivocally attributed to the viral
      enzyme. In an attempt to characterize other proteolytic activities that copurify
      with the virus, we isolated a multicatalytic high molecular mass protease (700
      kDa) that copurifies with the virus. This protein has been identified as an alpha
      2-macroglobulin-protein complex according to its biochemical properties and
      ultrastructure. The proteases forming these complexes are mainly serine proteases
      and can be inhibited by phenylmethylsulfonyl fluoride. However, other compounds
      such as chymostatin and elastatinal are more effective inhibitors. The relative
      efficacy of each compound depends on the substrate, since the complexes described
      herein appear to be multicatalytic. Elastatinal is a very good inhibitor of the
      cleavages found at Ala-Ala bonds in peptides representing the capsid/nucleocapsid
      site, while chymostatin inhibits certain cleavages at the carboxyl terminus of
      bonds involving leucine and valine in three of the substrates used. Therefore,
      the alpha 2-macroglobulin present in the cell culture medium is able to bind
      proteases, forming high molecular weight complexes, which are active against
      peptide substrates, copurify with the virus and are responsible for the nonviral
      proteolytic activities found in the purified virus. Elastase appears to be the
      main proteolytic activity which can be detected in the alpha 2-macroglobulin
      protease complexes associated with the virus.

PMID- 1375942
TI  - The sequence of the flavoprotein subunit of bovine heart succinate dehydrogenase.
AB  - The cDNA sequence of the flavoprotein subunit of bovine heart succinate
      dehydrogenase is reported. This is the first complete eukaryotic sequence of the
      flavoprotein subunit to be characterized, and it encodes a 665-amino acid protein
      that consists of a presequence and a 621-residue mature protein. The deduced
      bovine sequence shows homology to the corresponding peptides of prokaryotic
      succinate dehydrogenase and the related fumarate reductases; in particular, there
      is good overall homology (48%) to the flavoprotein subunit of Escherichia coli
      succinate dehydrogenase. The conserved sequences comprising the active site and
      those involved in FAD binding are also found in the bovine protein. The active
      site of the bovine polypeptide contains a cysteine that confers sensitivity of
      the enzyme to sulfhydryl reagents; this cysteine is only present in some
      sequences and thus provides a discriminatory biochemical marker. A putative
      flavoprotein subunit of human placental succinate dehydrogenase (partial
      sequence) that lacks this critical cysteine (Malcovati, M., Marchetti, T.,
      Zanelli, T., and Tenchini, M. L. (1991) in Flavins and Flavoproteins 1990 (Curti,
      B., Ronchi, S., and Zanetti, G., eds) pp. 727-730, Walter de Gruyter & Co.,
      Berlin) has only 16% homology to the bovine heart flavoprotein subunit. However,
      we show that the enzyme from human placenta is as sensitive to N-ethylmaleimide
      as that from bovine tissues. In addition, a transcript in human placenta and
      muscle hybridizes to the bovine heart flavoprotein cDNA and is the same size as
      that in bovine tissues.

PMID- 1375943
TI  - Cauliflower mosaic virus reverse transcriptase. Activation by proteolytic
      processing and functional alteration by terminal deletion.
AB  - We have previously expressed the cauliflower mosaic virus (CaMV) reverse
      transcriptase (RTase) gene, the ORFV gene, in yeast in an active form (RTase-Y).
      An activity gel analysis revealed that the molecular size of RTase-Y as well as
      an RTase associated with the CaMV particles (RTase-V) is 60 kDa. This size is
      about 18 kDa smaller than that of the inactive form previously expressed in
      Escherichia coli (RTase-E) (78 kDa), which corresponds to the coding capacity
      estimated for the ORFV gene. To investigate the possible involvement of
      proteolytic processing in the de novo synthesis of CaMV RTase, we constructed a
      series of deletions from either terminus or both termini of the ORFV coding
      sequence and expressed them in E. coli. Among the various truncated RTases, those
      (denoted delta N) that lack N-terminal peptide fragments 143-185 amino acids long
      were active on the synthetic RNA template-primer, poly(rC)-oligo(dG). Those
      RTases (denoted delta C) lacking C-terminal peptide fragments 50-102 amino acids
      long and those lacking both termini (denoted delta NC) were also active on this
      template. However, only the delta N RTases showed enzyme properties
      indistinguishable from the RTase-Y in that they transcribed natural RNA into DNA
      and required either Mg2+ or Mn2+ for their activity. The length of the deletion
      corresponded approximately to the difference of the molecular weights between
      RTase-Y and RTase-E. These results suggest that CaMV RTase is translated in an
      inactive precursor form and then converted to an active form by proteolytic
      processing during de novo synthesis. We have also demonstrated that C-terminal
      deletions cause a loss of activity on a natural RNA template accompanied by an
      alteration in metal ion requirement. The inability to incorporate dTTP accounts
      for the loss of activity on the natural RNA template. However, the affinities for
      dTTP and the corresponding template, poly(rA)-oligo(dT), were found to be
      unaltered.

PMID- 1375944
TI  - Elucidation of structural requirements on plasminogen activator inhibitor 1 for
      binding to heparin.
AB  - Plasminogen activator inhibitor 1 (PAI-1), a member of the serpin superfamily of
      proteins, has been demonstrated previously to interact functionally with the
      glycosaminoglycan heparin (Ehrlich, H.J., Keijer, J., Preissner, K. T., Klein
      Gebbink, R., and Pannekoek, H. (1991) Biochemistry 30, 1021-1028). Heparin
      specifically enhances the rate of association between PAI-1 and thrombin about 2
      orders of magnitude, whereas no effect is detected with other serine proteases
      (e.g. factor Xa). For the heparin-dependent serpins antithrombin III and heparin
      cofactor II, basic amino acid residues in and around the helix D subdomain were
      proposed to be involved in the binding of glycosaminoglycans. Here we employed
      site-directed mutagenesis of full-length PAI-1 cDNA to identify the amino acid
      residues that mediate heparin binding. To that end, 15 single-point mutants of
      PAI-1, each having individual arginyl, lysyl, or histidyl residues replaced by a
      neutral (alanyl) residue ("ala-scan"), and one double mutant were constructed,
      expressed in Escherichia coli, and purified to apparent homogeneity. The purified
      biologically active proteins were subjected to the following analyses: (i)
      heparin-dependent inhibition of thrombin; (ii) heparin-dependent formation of
      sodium dodecyl sulfate-stable complexes with thrombin; and (iii) binding to and
      elution from heparin-Sepharose. Based on the data presented, we propose that the
      amino acid residues Lys65, Lys69, Arg76, Lys80, and Lys88 constitute major
      determinants for heparin binding of PAI-1. These residues are located in and
      around the helix D domain and are conserved in the other heparin-dependent
      thrombin inhibitors, antithrombin III and heparin cofactor II.

PMID- 1375945
TI  - Reconstitution of interactions between the Src tyrosine kinases and Ras GTPase
      activating protein using a baculovirus expression system.
AB  - Ras GTPase-activating protein (GAP) has been implicated in mitogenic signal
      transduction downstream of oncogenic and receptor tyrosine kinases. Previous
      studies have suggested that GAP is phosphorylated by oncogenic viral Src (v-Src)
      and that GAP is associated with a complex containing normal cellular Src (c-Src)
      in vertebrate fibroblasts. To investigate molecular interactions between the Src
      kinases and GAP, we developed an in vitro system for reconstituting Src-GAP
      complexes. For this purpose, we constructed recombinant baculovirus vectors that
      direct expression of Rous sarcoma virus v-Src, chicken c-Src, and bovine GAP in
      infected Sf9 insect cells. In vitro reconstitution experiments using baculovirus
      expressed proteins demonstrate that both v-Src and c-Src associate in complexes
      with GAP. In addition, in vitro and in vivo phosphorylation analyses indicate
      that GAP serves as a substrate for both the v-Src and c-Src tyrosine kinases. To
      determine which structural features of GAP are involved in interactions with the
      Src kinases, we constructed recombinant baculoviruses that encode deletion
      mutants of bovine GAP. Deletion of the GAP amino-terminal portion containing Src
      homology 2 regions, which are highly conserved structural motifs postulated to
      mediate interactions among proteins, diminishes GAP phosphorylation and
      association with Src. This reconstitution system should facilitate further
      studies of molecular interactions between the Src kinases and GAP.

PMID- 1375946
TI  - The association of insulin-elicited phosphotyrosine proteins with src homology 2
      domains.
AB  - The interactions of the phosphotyrosine (Tyr(P))-containing proteins in basal and
      insulin-stimulated 3T3-L1 adipocytes with src homology 2 (SH2) domains from
      phosphatidylinositol 3-kinase (PI3K), ras GTPase-activating protein (GAP), and
      phospholipase C gamma have been examined. The Tyr(P) forms of the insulin
      receptor and its 160-kDa substrate protein (pp160) associated with fusion
      proteins containing either or both the SH2 domains of PI3K, but not with fusion
      proteins containing the two SH2 domains of GAP or phospholipase C gamma. These
      results demonstrate a specificity for the association of the Tyr(P) form of the
      insulin receptor and pp160 with SH2 domains that parallels the reported effects
      of insulin on PI3K, GAP, and phospholipase C gamma in vivo. Immunoprecipitates of
      pp160 from the cytosol of insulin-treated, but not basal, 3T3-L1 adipocytes
      contained PI3K activity. Moreover, the Tyr(P) form of pp160 with associated PI3K
      activity migrated at 10 S on a sucrose velocity gradient, whereas the Tyr(P) form
      without associated activity migrated at 6 S. These findings indicate that the
      Tyr(P) form of pp160 associates directly with PI3K in vivo.

PMID- 1375947
TI  - Benign prostatic hyperplasia: intervene or wait?

PMID- 1375948
TI  - HIV-1 sensitivity to zidovudine: a consensus culture technique validated by
      genotypic analysis of the reverse transcriptase.
AB  - In order to select and standardize a reliable assay for the analysis of
      sensitivity of HIV isolates to AZT, we have compared two culture methods. The
      first assay (Cell-Associated Isolate Sensitivity Assay: CAISA) quantified AZT
      resistant HIV isolates by end-point dilution cultures of peripheral blood
      mononuclear cells (PBMCs) in the presence of various concentrations of AZT. In
      the second assay (Cell-Free Isolate Sensitivity Assay: CFISA), following a
      conventional isolation of HIV, dilutions of infected cell-free supernatants were
      cultivated with fresh normal donor PBMCs in the presence of increasing
      concentrations of AZT. Samples from 64 untreated and AZT-treated patients were
      studied by CAISA (41), CFISA (43) or both assays (20). The CFISA, which allows
      the determination of titration parameters with respect to various kinetics
      patterns of viral replication was selected, and some of the CFISA phenotypically
      characterized isolates were further studied by nucleotide sequence analysis of
      the reverse transcriptase gene. CFISA showed that isolates from untreated
      patients were susceptible to AZT while the frequency of resistance increased with
      the duration of therapy. Genotypic analysis of CFISA-resistant isolates exhibited
      mutations at crucial positions, particularly at residue 215. We consider CFISA as
      a consensus culture technique for longitudinal studies of isolates from patients
      receiving AZT or other analogs of nucleosides.

PMID- 1375949
TI  - Use of Romanowsky type (Diff-3) stain for detecting Helicobacter pylori in smears
      and tissue sections.
AB  - A Romanowsky type (Diff-3) stain was used for identifying Helicobacter pylori in
      gastric biopsy specimens from 50 patients with ulcer and non-ulcer dyspepsia. Air
      dried smears were prepared from fresh biopsy tissue and histological sections
      were prepared from paraffin wax processed tissue. The Diff-3 technique is
      accomplished in five steps and takes about 30 seconds. Results using the Diff-3
      stain correlated 100% with those using the Giemsa stain. The Diff-3 stain is
      reliable, simple, rapid, easy and clean, and smears prepared from fresh biopsy
      tissue can be examined and an immediate report given. The method is recommended
      for the identification of H pylori in smears prepared from fresh tissue as well
      as in sections prepared from processed tissue.

PMID- 1375950
TI  - Fibrous mastocytoma in a patient with generalized cutaneous mastocytosis.
AB  - A 57-year-old woman with cutaneous mastocytosis of 23 years duration developed a
      hyperpigmented abdominal plaque composed of confluent indurated papules that
      enlarged for a period of 1 year to 12 x 8 cm. Biopsy showed dermal infiltration
      by closely packed spindle-shaped mast cells, fibroblasts, collagen, and scattered
      lymphocytes, predominantly T-suppressor cells. Electron microscopy showed close
      contact between mast cells, fibroblasts, and lymphocytes. Piecemeal mast cell
      degranulation and extrusion of mast cell granules was seen, with rare mast cell
      granules in fibroblasts, and collagen fibers in peripheral and perinuclear
      endoplasmic reticulum of mast cells. the term Fibrous mastocytoma is suggested
      for this tumor-like dermal fibrosis, possibly induced by lymphokines.

PMID- 1375951
TI  - Fibroepithelioma-like changes associated with anogenital epidermotropic mucinous
      carcinoma. Fibroepitheliomatous Paget phenomenon.
AB  - We describe two patients with crusted perineal plaques that were biopsied and
      diagnosed as Paget's disease. Resection specimens of each contained a dermal
      mucinous carcinoma with extensive epidermotropism and coexistent epidermal
      basaloid proliferations closely resembling fibroepithelioma (Pinkus). The
      presence of the Paget phenomenon was supported by histochemical,
      immunohistochemical, and ultrastructural evidence. No other primary neoplasms
      were found in either patient. Followup at 2 1/2 and 3 1/2 years, respectively,
      has been negative. We conclude that either the fibroepitheliomatous changes may
      be induced by or may represent a collison (unlikely) with the epidermotropic
      mucinous carcinoma. It is proposed that the concept fibroepitheliomatous Paget
      phenomenon be used to stand for the histologic changes common to our cases as
      well as those previously reported.

PMID- 1375952
TI  - Cutaneous lymphadenoma with focal mucinosis.
AB  - Cutaneous lymphadenoma of the eyebrow occurred in a 72-year-old man. The nodular
      tumor was well circumscribed but non encapsulated and invaded the reticular
      dermis and superficial hypodermis without any connection with the epidermis.
      Tumor cells had a basal-like appearance and were arranged in small lobules and
      islands with peripheral palisading and areas of central keratinization. They were
      often dissociated by an extracellular mucinous material. The stroma was
      fibroblastic and contained a marked lymphoid infiltrate that surrounded and
      penetrated the neoplastic lobules. Occasional germ-like hair follicle structures
      were noted. The immunohistochemical pattern was similar to that of hair
      follicles, and the leucocytic component was predominantly composed of T
      lymphocytes and Langerhans cells, which were specially numerous within the
      neoplastic lobules. We believe that the tumor, in the present case, has
      morphologic features consistent with epithelial and stromal attributes observed
      in hair follicles.

PMID- 1375953
TI  - Neurotropic malignant melanoma occurring in a stable burn scar.
AB  - Malignant melanoma occurring in burn scars is extremely rare. Nine cases are
      reported in the literature. We report a case of a small malignant melanoma
      arising in a stable thermal burn scar after a long latent period of 58 years. The
      case was unique in that it was of the de novo neurotropic variant. Fascicles of
      amelanotic, S100 protein-positive atypical spindle cells with neuroid appearance
      infiltrated deeply in the scarred dermis and perineural spaces. The pigmentation
      of the lesion was due to solar lentigo instead of atypical melanocytic
      proliferation in the overlying epidermis.

PMID- 1375954
TI  - Tricholemmal carcinoma: a study of seven cases.
AB  - Seven cases of tricholemmal carcinoma (TLC), a rarely recognized cutaneous
      adnexal neoplasm of external hair sheath origin, are described. Most occurred on
      sun-exposed skin; five involved the head and neck, one the right leg, and one the
      right thigh. TLC had a generally short history and all were treated by local
      excision. The lesions had an exophytic (3 cases) or polypoid (4 cases) gross
      appearance. Histologically, TLC exhibited a sharply circumscribed, lobular
      epithelial proliferation in continuity with the epidermis. A cytologic hallmark
      of these tumors was the presence of large cells with PAS-reactive, diastase
      sensitive, clear or pale eosinophilic cytoplasm. High mitotic rate was a constant
      feature. Four tumors were infiltrative, with pushing borders, whereas three were
      intraepithelial. One case showed acantholysis. Immunocytochemistry revealed
      positivity for prekeratin and negativity for CEA and EMA, supporting the
      trichogenic origin of these tumors. Ultrastructural examination gave clear
      indication of epithelial origin for the cells but did not verify hair follicular
      differentiation. Despite locally aggressive growth, the clinical course of TLC
      appeared indolent. Moreover, there are no cases with metastases reported in the
      literature.

PMID- 1375955
TI  - Antiallergic effect of epinastine (WAL 801 CL) on immediate hypersensitivity
      reactions: (I). Elucidation of the mechanism for histamine release inhibition.
AB  - Epinastine caused an inhibition of histamine release from rat peritoneal mast
      cells induced by both antigen-antibody reaction and compound 48/80. Epinastine
      was similarly effective in inhibiting compound 48/80-induced histamine release
      not only from isolated rat peritoneal mast cells but also from rat mesenterial
      pieces. Also, histamine release from lung pieces obtained from actively
      sensitized guinea pigs after exposure to antigen challenge was markedly inhibited
      by epinastine. The drug was effective in inhibiting not only Ca2+ uptake into
      lung mast cells in actively sensitized guinea pigs but also Ca2+ release from the
      intracellular Ca store of rat peritoneal mast cells exposed to both compound
      48/80 and substance P. No significant changes were observed in phosphodiesterase
      activity in rat peritoneal mast cells treated with epinastine, while adenylate
      cyclase activity was augmented by epinastine. Epinastine has no inhibitory effect
      on histamine release induced by Ca2+ or IP3 from permeabilized mast cells.
      However, the drug significantly and dose-dependently suppressed calmodulin
      activity suggesting that histamine release inhibition due to epinastine may be
      partly attributable to Ca(2+)-calmodulin dependent process(es). The drug caused
      no visible changes in thermodynamic behavior of lipids, either in order parameter
      or in differential scanning calorimetry, indicating that the drug has no
      influence on membrane fluidity.

PMID- 1375956
TI  - Immunomodulatory activity of a novel nucleoside, 7-thia-8-oxoguanosine. II.
      Characterization of induced effector cells and the mechanism of induction.
AB  - In a preceding paper we characterized the in vivo and in vitro induction of
      cytotoxic effector cells elicited by a novel synthetic immuno-stimulator 7-thia-8
      oxoguanosine (7T8OG)2. In the present study we further characterized the cells
      responsible for the induced cytotoxicity and the mechanisms together with the
      lymphokines mediating the immunological response to 7T8OG. Removal of macrophages
      from 7T8OG activated spleen cell suspensions by various methods resulted in a
      significant increase in cytotoxicity to YAC-1 targets. 7T8OG induced effectors
      did not exert cytotoxic effect on macrophage sensitive P815 target cells. In vivo
      activated effectors when incubated with anti-asialo-GM1 antibody plus complement
      lost completely their ability to lyse YAC-1 targets. Together, these findings
      indicate that the 7T8OG induced effector cells are not macrophage like. Spleen
      cells from nude mice were readily activated by 7T8OG. The induced effectors were
      resistant to complement mediated lysis using anti-L3T4, anti-Lyt1 or anti-Lyt2
      antibodies. Pretreatment of spleen cells with macrophage depleting agents both,
      in vitro and in vivo and subsequent activation of cells by 7T8OG resulted in
      effectors with reduced cytotoxicity. When injected in vivo, 7T8OG induced strong
      IFN production which paralelled the kinetics of NK cell activation. Furthermore,
      antibodies to alpha & beta-IFN but not to gamma-IFN diminished the induction of
      the cytotoxic activity. Although these findings suggest that activation of NK
      cells by 7T8OG is most likely to be mediated by alpha & beta-IFN involvement of
      other cytokines can not be ruled out.

PMID- 1375957
TI  - Immunomodulatory effects of gamma-HCH (Lindane) in mice.
AB  - Mice were fed for 24 weeks with three different subtoxic dosages of gamma-HCH
      (0.012, 0.12 and 1.2 mg/kg) mixed in powdered feed. The immunological profile was
      assessed at an interval of one month during the entire exposure period. Both the
      cell mediated and humoral components of immunity showed a biphasic response
      characterized initially by stimulation followed by suppression in a dose
      dependent manner. However, gamma-HCH did not affect the functional properties of
      peritoneal macrophages. Histological changes in lymphoid organs were in
      accordance with the biphasic immunomodulatory effects of gamma-HCH.

PMID- 1375959
TI  - Isotype determination of anti-Trypanosoma cruzi antibody in murine Chagas'
      disease.
AB  - Isotypic analysis of anti-parasite humoral responses of C57B1/6 and C3H (He) mice
      surviving acute Trypanosoma cruzi infection showed that both mouse strains
      demonstrate IgG1, IgG2a, IgG2b, and IgM enzyme-linked immunosorbent assay titers
      from days 21 to 300 of infection. Using the western blot technique to determine
      the antigen specificity of the isotypic responses, 100-day infected C3H mice
      showed strong IgG1, IgG2a, and IgG2b responses to many antigens, whereas C57B1/6
      mice showed weak responses to fewer antigens. Isotype western blots showed that
      reactivity to the T. cruzi antigen of 75-77 kDa is present in the humoral
      response of day 21-infected mice that will survive and missing in those that will
      not survive. In general, surviving immunized C3H mice respond with IgG1, IgG2a,
      and IgG2b reactions to the 75-77-kDa and other antigens, whereas resistant B6
      mice concentrate their anti-T. cruzi response in the IgG2b isotype to the 75-77
      kDa antigen. Perhaps induction of ineffective antibody responses to nonprotective
      antigens is beneficial to the parasite and detrimental to the host.

PMID- 1375960
TI  - The biochemical defect in cystic fibrosis.

PMID- 1375961
TI  - The gene defect in cystic fibrosis and clinical applications of the knowledge.

PMID- 1375958
TI  - Role of GTP-binding proteins in the regulation of mammalian cardiac chloride
      conductance.
AB  - Beta-Adrenoceptor agonists activate a time- and voltage-independent Cl-
      conductance in mammalian cardiac myocytes. To characterize the cellular signaling
      pathways underlying its regulation, wide-tipped pipettes fitted with a pipette
      perfusion device were used to record whole-cell current and to introduce
      nucleotides to the interior of guinea pig ventricular myocytes. Replacement of
      pipette GTP with GDP beta S prevented activation of the Cl- conductance by Iso,
      suggesting a requirement for G protein turnover. With GTP in the pipette, the
      effect of Iso could be abolished by the beta-adrenoceptor antagonist propranolol,
      and mimicked by histamine or forskolin. These actions of Iso and forskolin are
      mediated exclusively via cAMP-dependent protein kinase (PKA), because (a) maximal
      activation of the Cl- conductance by forskolin or pipette cAMP occluded the
      effect of Iso, and (b) switching to pipette solution containing a synthetic
      peptide inhibitor (PKI) of PKA completely abolished the Cl- conductance activated
      by Iso and prevented the action of forskolin, but had no further effect. These
      results argue against basal activation of the Cl- conductance, and make it
      extremely unlikely that the stimulatory G protein, Gs, has any direct,
      phosphorylation-independent influence. The muscarinic receptor agonists
      acetylcholine (ACh) and carbachol diminished, in a reversible manner, Cl-
      conductance activated by Iso or forskolin, but not that elicited by cAMP. The
      muscarinic inhibition was abolished by replacing pipette GTP with GDP beta S, or
      by preincubating cells with pertussis toxin (PTX), and was therefore mediated by
      an inhibitory G protein, presumably Gi, influencing adenylyl cyclase activity.
      Nonhydrolyzable GTP analogues (GTP gamma S or GppNHp) applied via the pipette did
      not themselves activate Cl- conductance, but rendered Cl- current activation by
      brief exposures to Iso or histamine, but not to forskolin, irreversible. The Cl-
      conductance persistently activated by Iso was insensitive to propranolol or ACh,
      but could still be abolished by pipette application of PKI. The data indicate
      that stimulation of beta-adrenergic or histaminergic receptors in the presence of
      nonhydrolyzable GTP analogues causes persistent activation of Gs and uncouples it
      from the receptors. We conclude that autonomic regulation of cardiac Cl-
      conductance reflects accurately the underlying modulation of adenylyl cyclase
      activity and, hence, that this system is a suitable mammalian model for in situ
      studies of the interactions between adenylyl cyclase, Gs, Gi, and forskolin.

PMID- 1375962
TI  - New thymidine triphosphate analogue inhibitors of human immunodeficiency virus-1
      reverse transcriptase.
AB  - Several novel imidotriphosphate analogues of thymidine have been synthesized and
      have been shown to be effective inhibitors of human immunodeficiency virus-1
      reverse transcriptase (HIV-1 RT). When the alpha,beta-bridging oxygens of
      thymidine triphosphate (TTP) and 3'-azido-3'-deoxythymidine 5'-triphosphate
      (AZTTP) were replaced by a nitrogen, the resulting analogues were no longer
      substrates but instead became competitive inhibitors of HIV-1 RT. The most potent
      of the alpha,beta-imidotriphosphate derivatives tested was thymidine 5'
      [alpha,beta-imido]triphosphate (TMPNPP, 1a). This analogue has a Ki value of 2.4
      microM, inhibiting HIV-1 RT 400-fold more potently than it inhibits DNA
      polymerase I large fragment (Klenow). 3'-Azido-3'-deoxythymidine 5'-[alpha,beta
      imido]triphosphate (AZTMPNPP, 1b) gave a Ki value about 10-fold greater than that
      for TMPNPP, indicating that a 3'-azido substituent decreases the affinity of
      AZTTP to HIV-1 RT relative to the normal 3'-OH substituent. Dideoxythymidine 5'
      [alpha,beta-imido]triphosphate (ddTMPNPP, 1c) was intermediate in potency, giving
      a Ki value of 15 microM. In contrast, substitution at the beta,gamma-bridging
      oxygen by nitrogen did not block the enzymatic cleavage of the adjacent
      alpha,beta-phosphate linkage, and 3'-azidothymidine 5'-[beta,gamma
      imido]triphosphate (AZTMPPNP, 1e), the 5'-[beta,gamma-imido]triphosphate analogue
      of AZTTP, is therefore both a substrate for and a potent inhibitor of HIV-1 RT
      with an observed Ki value of 87 nM. Further nitrogen substitution of the bridging
      oxygens in the phosphate chain decreases the inhibitory potency by approximately
      10-fold, as in the case of thymidine 5'-[alpha,beta:beta,gamma
      diimido]triphosphate (TMPNPNP, 1d).

PMID- 1375963
TI  - Synthesis and biological evaluation of N alpha-(5-deaza-5,6,7,8
      tetrahydropteroyl)-L-ornithine.
AB  - A novel folic acid analogue, N alpha-(5-deaza-5,6,7,8-tetrahydropteroyl)-L
      ornithine, 3, was prepared via a multistep synthetic sequence. The key steps
      involved the conversion of 5-deazapteroic acid to its N10-formyl derivative
      followed by catalytic hydrogenation of the pyridine ring and subsequent heating
      in dilute sodium hydroxide to afford the new 5-deaza-5,6,7,8-tetrahydropteroic
      acid. After trifluoroacetylation, this compound was coupled to N delta-(tert
      butyl-oxycarbonyl)-L-ornithine using conventional peptide bond forming
      conditions. Deprotection first in base and then in acid gave the title compound.
      Compound 3 was an effective inhibitor of hog liver folylpolyglutamate synthetase
      (Kis, estimated = 64 nM), and was shown to retard the formation of polyglutamates
      of a structurally related folic acid analogue in HCT-8 cells in vitro.

PMID- 1375964
TI  - Development of potent and selective CCK-A receptor agonists from Boc-CCK-4:
      tetrapeptides containing Lys(N epsilon)-amide residues.
AB  - A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp
      Lys(N epsilon-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or
      aliphatic group, are potent and selective CCK-A receptor agonists. These amide
      bearing compounds complement the previously described urea-based tetrapeptides
      (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842); structure-activity studies
      revealed parallel as well as divergent trends between these two series. A
      significant correlation was observed between pancreatic binding affinity and the
      resonance constant R of the phenyl substituent in one particular series of
      derivatives. Sulfation of phenolic amides appended onto the epsilon-amino group
      of the lysine did not affect affinity for the CCK-A receptor in contrast to the
      500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting
      that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural
      elements that impart high affinity for the CCK-A receptor, are interacting
      differently with the receptor. The amide-bearing tetrapeptides are full agonists
      relative to CCK-8 in stimulating pancreatic amylase release while being partial
      agonists in eliciting phosphoinositide (PI) hydrolysis. Both effects were blocked
      by selective CCK-A receptor antagonists.

PMID- 1375965
TI  - Studies on neurokinin antagonists. 1. The design of novel tripeptides possessing
      the glutaminyl-D-tryptophylphenylalanine sequence as substance P antagonists.
AB  - To discover a novel and low molecular weight substance P (SP) antagonist we
      postulated that the essential binding domain of peptide ligands was only a small
      portion in the whole structure. On the basis of this assumption, we selected the
      known octapeptide SP antagonist D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Phe-NH2 (1)
      as a lead and synthesized its fragment tripeptides which were evaluated for their
      activity to block 3H-SP binding on guinea pig lung membranes. The protected
      tripeptide N alpha-[N alpha-[N alpha-(tert-butyloxycarbonyl)-L-glutaminyl]-N1
      formyl-D-tryptophyl]- L-phenylalanine benzyl ester [Boc-Gln-D-Trp(CHO)-Phe-OBzl
      (4a)], corresponding to the Gln-D-Trp-Phe part of 1, exhibited 7-fold potent
      inhibitory activity in comparison with 1. Studies on structure-activity
      relationships revealed that the D-tryptophan, L-phenylalanine, and benzyl ester
      were quite important to maintain the high binding affinity. It was also indicated
      that 4a antagonized the SP-induced contraction of isolated guinea pig trachea
      strips (IC50 = 4.7 x 10(-6) M).

PMID- 1375967
TI  - The immunosuppressive effect of FK 506 on canine lung transplantation.
AB  - The immunosuppressive potency of FK 506 was studied after left lung
      transplantation in adult mongrel dogs in comparison with cyclosporine. Fiberoptic
      bronchoscopy, bronchial mucosal blood flow measurement with laser Doppler
      velocimetry, and chest x-ray and pathologic examinations were performed. Group A
      had no immunosuppression (n = 5); group B received FK 506 (0.10 mg/kg/day
      intramuscularly (n = 5); group C received cyclosporine (20 mg/kg/day orally) (n =
      5). In group A four dogs died of rejection on the seventh to the twenty-first
      postoperative days. Another one was killed on the fourteenth postoperative day
      because bronchial dehiscence occurred at the anastomosis. In group B one died of
      alveolar rejection on the seventh postoperative day. The remaining four survived
      28 days and were put to death. In group C all five dogs survived 28 days and were
      put to death. In group A bronchial stenosis or dehiscence at the anastomosis was
      found in every one during the early postoperative period. In group B stenosis did
      not develop in any of the dogs, including the one that died on the seventh
      postoperative day. In group C slight stenosis was seen in one dog, severe
      narrowing in another, and good healing in the remaining three. The transplanted
      lungs were almost normal histologically in four animals of group B, and one
      showed alveolar phase rejection. In all animals of group A severe rejection was
      observed, and in group C two of five animals showed vascular phase rejection, two
      latent phase, and one fibrosis. Histologic examination of the bronchial
      anastomosis in group B showed almost normal bronchial epithelium and slight
      submucosal infiltration of mononuclear cells. In group A there was desquamation
      of epithelium and mild to moderate mononuclear cell infiltration. In group C
      hyperplasia of the epithelium was observed in two animals, an abscess at the site
      of anastomosis in one, and mild to moderate mononuclear cell infiltration in all
      five. With use of laser Doppler velocimetry, bronchial blood flow in group B was
      found to be the same as in group C. Laser Doppler velocimetry values reached
      preoperative levels by the twenty-eighth postoperative day in both groups.
      Although diarrhea developed in two dogs of group B, no other significant side
      effect of FK 506 was seen.

PMID- 1375966
TI  - High-dose heparin suppresses platelet alpha granule secretion.
AB  - Platelet degranulation has been implicated in the pathophysiology of acute
      arterial thrombosis, intimal hyperplasia, and atherogenesis. Most previous
      studies that examined the effect of heparin on platelet function have used
      platelet aggregometry. These studies have resulted in contradictory data and, by
      the nature of the assay, reveal no information with regard to platelet
      degranulation. In contrast, flow cytometry allows accurate quantification of the
      extent of platelet degranulation by measurement of the platelet surface binding
      of a GMP-140 specific monoclonal antibody (S12). GMP-140 is only expressed on the
      platelet surface after platelet alpha granule release. In the present study
      increasing concentrations of heparin were added to whole blood anticoagulated
      with sodium citrate. Platelets were activated with a panel of agonists, and the
      extent of platelet degranulation was quantified by whole blood flow cytometry.
      Heparin concentrations as high as 100 units/ml were found to suppress platelet
      alpha granule release induced by either a thromboxane A2 analog (U46619) or a
      combination of adenosine diphosphate and epinephrine. Heparin suppressed alpha
      granule release induced by thrombin both in whole blood and in washed platelets.
      The addition of heparin after platelet activation had no effect on S12 binding.
      In summary, heparin in high concentrations is a potent inhibitor of platelet
      degranulation, an action that is unrelated to its effect on the coagulation
      cascade. Although the heparin concentrations used in this study exceed those used
      clinically by a factor of 10 or more, future studies of heparin fractions may
      allow the separation of the anticoagulant and antiplatelet properties of the
      molecule and allow the administration of an agent that selectively suppresses
      platelet degranulation without the humoral anticoagulant effect.

PMID- 1375968
TI  - Pseudomonas cepacia--more than a harmless commensal?

PMID- 1375969
TI  - G-CSF and peripheral blood progenitor cells.

PMID- 1375970
TI  - G-CSF and peripheral blood progenitor cells.

PMID- 1375971
TI  - G-CSF and peripheral blood progenitor cells.

PMID- 1375972
TI  - Ondansetron in carcinoid syndrome.

PMID- 1375973
TI  - Role of nitric oxide in the oxidant stress during ischemia/reperfusion injury of
      the liver.
AB  - The potential role of nitric oxide (NO) and its reaction product with superoxide,
      peroxynitrite, was investigated in a model of hepatic ischemia-reperfusion injury
      in male Fischer rats in vivo. Pretreatment with the NO synthase inhibitor nitro-L
      arginine (10 mg/kg) did neither affect the post-ischemic oxidant stress and liver
      injury during the initial reperfusion phase nor the subsequent infiltration of
      neutrophils into the liver and the later, neutrophil-induced injury phase.
      Furthermore, no evidence was found for a postischemic increase of the urinary
      excretion of nitrite, a stable oxidation metabolite of NO. In contrast, the
      administration of Salmonella enteritidis endotoxin (1 mg/kg) induced a
      significant diuresis in Fischer rats and an 800-fold enhancement of the urinary
      nitrite excretion. Nitro-L-arginine pretreatment inhibited the endotoxin-induced
      nitrite formation by 97%. Hepatic cGMP levels, as index of NO formation in the
      liver, were only increased significantly after endotoxin administration but not
      after ischemia and reperfusion. Our results provide no evidence for any enhanced
      generation of NO or peroxynitrite either systemically or locally during
      reperfusion and therefore it is unlikely that any of these metabolites are
      involved in the oxidant stress and liver injury during reperfusion after hepatic
      ischemia.

PMID- 1375975
TI  - Granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor (1).

PMID- 1375974
TI  - Antinociceptive effects of intrathecal taurine and calcium in the mouse.
AB  - Taurine (Tau), calcium (Ca+2) and opiates each produce antinociception when
      injected i.t. in mice. This study was initiated to determine whether there is a
      common mechanism underlying their antinociceptive effects. Using the abdominal
      stretch assay, the antinociceptive effects of both Tau (12 nmol) and Ca+2 (72
      nmol) were antagonized by i.t. TAG (4.4 nmol), a Tau antagonist, but not by i.p.
      injection of the opiate antagonist naloxone (5 mg/kg). The antinociceptive
      effects of Tau and Ca+2 correlated with their ability to inhibit the intensity of
      caudally-directed biting and scratching behaviors produced by i.t. NMDA or kainic
      acid. The inhibitory effects of both Tau and Ca+2 on the biting and scratching
      behaviors behaviors induced by substance P or excitatory amino acids were
      reversed by TAG, suggesting a common mediation by Tau. These data indicate that
      the antinociceptive effects of both Tau and Ca+2 appear to be mediated, at least
      in part, by Tau but not by the release of endogenous opioid compounds. In
      addition, inhibition of chemical irritant-induced nociception may be produced by
      a simple blockade of excitatory amino acid activity.

PMID- 1375976
TI  - [Use of lectins for the study of carbohydrate determinants of cholinoreceptors of
      various subtypes in mollusk neurons].
AB  - Chemical nature of carbohydrate components in identified neurons of mollusc Helix
      pomatia influencing acetylcholine responses was investigated using different
      lectins (Con A, RCA, WGA and LPA). Differences between Con A-evoked changes in
      acetylcholine-induced chloride and sodium-potassium currents as well as
      differences in the time and temperature dependences of these changes showed
      various mechanisms of action of carbohydrate component with mannose residues on
      the function of acetylcholine receptors. The analysis of the time and temperature
      dependences of depressing effects of WGA and RCA on acetylcholine-induced
      currents permits supposing endocytosis of lectin-receptor complexes with N-acetyl
      D-glucosamine residues.

PMID- 1375977
TI  - Comparison of late and early stage surgery for ruptured intracranial aneurysms.
AB  - Surgical indications and timing in serious cases (Hunt and Hess grades 4 and 5)
      of intracranial aneurysms were investigated. The outcomes in early surgery were
      compared to the clinical courses of cases intended for late surgery. The survival
      rate of early surgery patients was 64.4%, better than the total of improved
      (28.3%) and survived (6.5%) patients for late surgery. There were 28.8% good
      outcomes in the early surgery group, compared to 2.2% in those treated late. Both
      of these figures are statistically significant. We consider that early surgery is
      indicated for serious cases, but not for grade 5 patients with hematoma.

PMID- 1375978
TI  - Microprolactinoma invading the cavernous sinus--report of three cases.
AB  - Three cases of microprolactinoma with cavernous sinus invasion on magnetic
      resonance imaging are reported. High-resolution computed tomographic scans did
      not demonstrate the cavernous sinus involvement. Magnetic resonance imaging is
      indispensable to detect cavernous sinus invasion before treatment
      (transsphenoidal surgery or bromocriptine treatment) of a microprolactinoma.

PMID- 1375979
TI  - Repeated intracerebral hemorrhage associated with impaired platelet aggregation-
      report of two cases.
AB  - The authors report two cases of hypertensive intracerebral hemorrhage (ICH)
      repeated at the same site within 1 or 2 days causing death in a 53-year-old male
      and a 48-year-old female. In both cases, platelet aggregation was significantly
      impaired. Acquired platelet dysfunction may be important in the expansion of
      hemorrhage in patients with repeated hypertensive ICH. In such cases
      administration of normal platelets may be required to prevent devastating
      hemorrhage.

PMID- 1375980
TI  - Ruptured anterior communicating artery aneurysm causing bilateral abducens nerve
      paralyses--case report.
AB  - A rare case of bilateral abducens nerve paralyses after rupture of an anterior
      communicating artery (AcoA) aneurysm occurred in a 56-year-old female after
      sudden onset of severe headache. Bilateral abducens nerve paralyses were present
      without additional neuro-ophthalmological signs. Computed tomography revealed
      subarachnoid hemorrhage (SAH). Angiography showed an AcoA aneurysm (15 mm in
      diameter, directed antero-inferiorly) that was successfully clipped.
      Postoperatively, the bilateral abducens nerve paralyses gradually recovered and
      disappeared 3 months after onset. Bilateral abducens nerve paralyses may occur
      after SAH due to ruptured AcoA aneurysm, and neurosurgeons should be alert to
      this possibility.

PMID- 1375981
TI  - Surgical treatment of extracranial distal internal carotid artery dissecting
      aneurysm--case report.
AB  - A 53-year-old male presented with a dissecting aneurysm of the extracranial
      distal internal carotid artery (ICA) treated by aneurysm removal with
      interposition of a saphenous vein graft. The surgical approach involved
      sectioning of Riolan's nosegay.

PMID- 1375982
TI  - Delayed postcontrast CT and MR imaging of chondroid chordoma--case report.
AB  - A rare case of intracranial primary chondroid chordoma is reported with special
      reference to neuroradiological findings. A precontrast computed tomographic (CT)
      scan revealed an isodense mass with multiple flecks in the right cerebellopontine
      region. A postcontrast CT scan showed slight ring enhancement. A delayed
      postcontrast CT scan demonstrated marked homogeneous enhancement extending from
      the middle cranial fossa to the cerebellopontine region on the right. Magnetic
      resonance (MR) imaging demonstrated a well-defined lesion as a high-intensity
      mass on T2-weighted image and a low-intensity mass on T1-weighted image. A MR
      image 5 minutes after gadolinium-diethylenetriaminepenta-acetic acid
      administration showed heterogeneous enhancement. A MR image 30 minutes after the
      contrast administration showed more marked, homogeneous enhancement. Such delayed
      postcontrast CT and MR imaging are useful in the differentiation of chondroid
      chordoma from classical chordoma.

PMID- 1375983
TI  - Radiation-induced osteosarcoma of the calvaria--case report.
AB  - The authors report a case of radiation-induced calvarial osteosarcoma. A 58-year
      old female received subtotal removal of the pituitary adenoma and 5000 rads
      postoperative irradiation. Seven years later, an osteoblastic osteosarcoma
      occurred in the frontotemporal region. She received total tumor removal and
      chemotherapy. However, computed tomography subsequently revealed multiple small
      lesions at the margin of the bone flap. A chest x-ray film demonstrated lung
      metastasis. Local recurrence and lung metastasis require careful attention in
      radiation-induced osteosarcoma patients.

PMID- 1375984
TI  - Subfascial temporalis dissection preserving the facial nerve in pterional
      craniotomy--technical note.
AB  - The subfascial temporalis dissection and reconstruction of the temporalis muscle
      for pterional craniotomy are described. These procedures preserve the
      frontotemporal branch of the facial nerve and increase exposure along the
      sphenoid ridge. A good cosmetic appearance and good temporalis muscle function
      are achieved postoperatively.

PMID- 1375985
TI  - Modified head fixation system for intraoperative CT scanning--technical note.
AB  - A head fixation system using four carbon fiber head pins and modified pin
      supporting devices is described. The fixation system was developed for
      intraoperative computed tomographic scanning and provides artifact-free images
      during open-field neurosurgery.

PMID- 1375986
TI  - Grading and scoring system for neurological function in degenerative cervical
      spine disease--Neurosurgical Cervical Spine Scale.

PMID- 1375987
TI  - STA-MCA bypass surgery for internal carotid artery occlusion--comparative follow
      up study.
AB  - Sixty-three patients with internal carotid artery occlusion manifesting as
      transient ischemic attack or minor stroke received superficial temporal artery
      middle cerebral artery bypass surgery and medical treatment (n = 27) or medical
      treatment only (n = 36). Long-term follow-up showed that there was no significant
      difference in the outcomes. However, positron emission tomography studies
      suggested that patients with misery perfusion in the chronic stage benefited from
      extracranial-intracranial bypass surgery.

PMID- 1375988
TI  - Ruthenium red affects the contractile apparatus but not sarcoplasmic reticulum
      Ca2+ release of skinned papillary muscle.
AB  - Ruthenium red has been shown to have a positive inotropic effect on isolated
      perfused hearts. The cellular mechanism of this action is not clear. Ruthenium
      red is able to block the Ca2+ release channel in isolated sarcoplasmic reticulum
      (SR) vesicle and reconstituted channel preparations. However, the effect of
      ruthenium red on SR Ca2+ release has not been studied in skinned cardiac muscle
      preparations. In the present study we investigated the actions of ruthenium red
      on both the characteristics of force generation by the contractile apparatus and
      Ca2+ release from the SR in chemically skinned rat papillary muscle. Ruthenium
      red (2 and 10 microM) significantly increased the Ca2+ sensitivity of the
      contractile apparatus (decreasing Ca2+ required for the half-maximal response
      from 1.56 +/- 0.04 microM to 1.46 +/- 0.05 microM) but had no effect on the
      maximal Ca(2+)-activated force in triton X-100 treated fibers. This result may
      suggest one explanation for the positive inotropic effect of ruthenium red on the
      heart. On the other hand, ruthenium red had no significant effect on either
      caffeine-induced Ca2+ release or Ca(2+)-induced Ca2+ release from the SR in
      saponin-skinned muscle fibers. Lack of a blocking effect on SR Ca2+ release by
      ruthenium red in skinned fibers suggests that the SR Ca2+ channels in intact
      preparations have characteristics that are different from those of either
      vesicular or reconstituted channel preparations.

PMID- 1375989
TI  - Activation of nonselective cation channels in the basolateral membrane of rat
      distal colon crypt cells by prostaglandin E2.
AB  - Ion channels in the basolateral membrane of colonic crypts were investigated with
      the patch-clamp technique during stimulation of secretion. Intact crypts were
      isolated from rat distal colon and the cell potential was recorded by addition of
      nystatin to the pipette solution. The cell resting potential in the base of the
      crypt was -74 +/- 1 mV (n = 90). Addition of 100 microM carbachol to the bath
      resulted in a transient hyperpolarization by 9 mV, which was probably due to the
      opening of basolateral K+ channels. In contrast, application of prostaglandin E2
      (PGE2, 1 nM-1 microM) caused a dose-dependent depolarization in the base of the
      crypt. With 1 microM PGE2 cells depolarized from -74 +/- 1 to -27 +/- 2 mV (n =
      26). Cell potential recordings in the midcrypt showed only a slight and transient
      depolarization after application of PGE2, whereas cells close to the surface of
      the crypt had no response. In the base of the crypt the PGE2-induced
      depolarization could be completely inhibited by addition of 50 microM flufenamic
      acid, a known blocker of nonselective cation channels. After substitution of all
      monovalent cations by N-methyl-D-glucamine in the bath, PGE2 had no significant
      effect on the cell potential. Cell-attached experiments with no nystatin in the
      patch pipette revealed the activation of ion channels in the basolateral membrane
      after application of PGE2. After excision of the membrane patch, these channels
      could be identified as nonselective cation channels. Experiments involving
      substitution of the bath solution showed that the channel is impermeable for Cl-
      and scarcely permeable for Ca2+ ions. The permeability sequence for monovalent
      cations, as calculated from reversal potentials, is NH4+ greater than Na+ = K+
      greater than Rb+ = Li+ much greater than TRIS+ = NMDG+. Single channels are
      completely inhibited by flufenamic acid (50 microM), mefenamic acid (200 microM),
      as well as by 3',5-dichlorodiphenylamine-2-carboxylate. In conclusion, PGE2
      activates nonselective cation channels in the basolateral membrane of cells in
      the base of colonic crypts. It is suggested that this mechanism initiates the
      secretion of K+ ions. Na+ influx through the nonselective cation channel will
      stimulate the Na+/K+ pump and active uptake of K+ at the basolateral side. K+ can
      leave the cell at the luminal side through K(+)-selective channels.

PMID- 1375990
TI  - Effects of activators and inhibitors of protein kinase A on increases in quantal
      size at the frog neuromuscular junction.
AB  - Adrenaline, permeable cyclic adenosine monophosphate (cAMP) derivatives and
      insulin are known to elicit an increase in quantal size at the frog neuromuscular
      junction, primarily by increasing the amount of acetylcholine (ACh) per quantum.
      The quantal size increases produced by adrenaline or cAMP were antagonized by the
      protein kinase inhibitor H8 N-[2-(methylamino)ethyl]-5-isoquinolonesulfonamide.
      The increase in quantal size produced by insulin was not prevented by H8. Quantal
      size is also increased by pretreatment in hypertonic solution; this increase was
      also antagonized by H8. The H8 did not alter the increase in miniature endplate
      potential (MEPP) frequency produced by the hypertonic solution. A permeable cGMP
      derivative had no effect on quantal size. The diastereomer (Sp)-cAMPS (cyclic
      3',5'-phosphothoate) activates protein kinase A(PKA). It elicited an increase in
      quantal size. The (Rp)-cAMPS isomer is known to inhibit PKA; it had no effect on
      quantal size. The increase in quantal size produced by hypertonic solution was
      antagonized by (Rp)-cAMPS but not by (Sp)-cAMPS. Brief exposure to a hypertonic
      solution containing a phosphodiesterase inhibitor followed by incubation in the
      inhibitor leads to an increase in quantal size. We conclude that one pathway for
      signaling for an increase in quantal size involves activation of PKA and that
      hypertonic pretreatment acts via this pathway.

PMID- 1375991
TI  - Mechanism of acetylcholine action on pacemaker current (i(f)) in canine Purkinje
      fibers.
AB  - We have recently reported in canine Purkinje fibers that acetylcholine (ACh) can
      reverse the positive voltage shift of the pacemaker current (i(f)) induced by
      beta-adrenergic stimulation while having no direct action of its own. We have now
      investigated this effect of ACh on the cyclic adenosine monophosphate (cAMP)
      cascade in more detail. We find that addition of a membrane permeable analogue of
      cAMP (8-chlorophenylthio cAMP), 0.5-1 mM, increased the amplitude of i(f). This
      action was not reversed by 1 microM ACh, implying that ACh acts at a step prior
      to cAMP action. We then looked at the steps controlling intracellular
      concentration of cAMP. Inhibiting the phosphodiesterase with 100 microM isobutyl
      1-methylxanthine (IBMX) increased i(f). This action, however, was reversed by
      ACh. Finally we investigated whether the action of forskolin, a direct activator
      of adenylyl cyclase, could be reversed by ACh. Forskolin (10-20 microM) increased
      i(f), and ACh at 1 microM partially reversed this action of forskolin. These
      results suggest that, in canine Purkinje fibers, ACh reverses the positive action
      of beta-adrenergic agents on i(f) via a decrease in cAMP production.

PMID- 1375992
TI  - DNA synthesis blocking lesions induced by singlet oxygen are targeted to
      deoxyguanosines.
AB  - In vitro DNA synthesis on single stranded templates damaged by singlet oxygen was
      investigated in the supF tRNA gene sequence, using several DNA polymerases.
      Singlet oxygen was generated by the thermal decomposition of the water soluble
      with the endoperoxide of disodium 3,3'-(1,4-naphthylidene) dipropionate (NDPO2).
      The data demonstrated that damage at deoxyguanosine residues interrupts DNA
      polymerization. Modified T7 phage and Thermus aquaticus DNA polymerases were
      found to synthesize DNA fragments which terminated opposite deoxyguanosine, while
      T4 phage DNA polymerase and avian myeloblast virus reverse transcriptase were
      blocked one nucleotide 3' to deoxyguanosine positions on the template. DNA
      polymerase I (Klenow fragment) from Escherichia coli was inhibited at both
      positions, before and at the putative damaged sites. The blocking lesions,
      induced by 5 mM NDPO2, were estimated to be approximately 1.5 per 260
      nucleotides, corresponding to 2% of deoxyguanosines. The distribution of lesions
      in the supF gene did not reveal any specific sequence context which showed
      distinct susceptibility to the attack of singlet oxygen.

PMID- 1375994
TI  - The PIR-International Protein Sequence Database.

PMID- 1375993
TI  - Human HeLa cell enzymes that remove phosphoglycolate 3'-end groups from DNA.
AB  - We have purified three chromatographically distinct human enzyme activities from
      HeLa cells, that are capable of converting bleomycin-treated DNA into a substrate
      for E. coli DNA polymerase I. The bleomycin-treated DNA substrate used in this
      study has been characterized via a 32P-postlabeling assay and shown to contain
      strand breaks with 3'-phosphoglycolate termini as greater than 95% of the
      detectable dose-dependent lesions. The purified HeLa cell enzymes were shown to
      be capable of removing 3'-phosphoglycolates from this substrate. Also 3'
      phosphoglycolate removal and nucleotide incorporation were enzyme dependent. In
      addition, all three Hela cell enzymes have been determined to possess Class II AP
      endonuclease activity. The enzymes lack 3'----5' exonuclease activity and are,
      therefore, dissimilar to exonuclease III--an E. coli enzyme that can remove 3'
      phosphoglycolate.

PMID- 1375995
TI  - Compilation of small ribosomal subunit RNA sequences.

PMID- 1375998
TI  - Symbolic association between individuals and objects by a chimpanzee as an
      initiation of ownership.
AB  - A chimpanzee, named Ai, received feeding training with two other apes. Ai was
      always fed with the green bowl; the other two apes were fed with different
      colored bowls. After this training, Ai could make symbolic associations between
      objects and individuals by using an artificial visual language, based only on her
      observation of bowls used in feeding without specific training.

PMID- 1375999
TI  - [The effect of chronic gamma irradiation in an exponentially decreasing dose rate
      on the nucleic acid content in the hematopoietic organs and blood of rats].
AB  - The effect of continuous gamma irradiation at exponentially decreased dose rates
      (from 562 mGy/h to 13 mGy/h with a total cumulative dose of 14.355 Gy delivered
      over a period of 10 days) on the nucleic acid content of rat hemopoietic tissues
      and blood was followed up. The radiation model used simulated a decrease in the
      radioactivity of a fission mixture in the contaminated environment resulting from
      a nuclear device accident. We have found that the dynamics of the changes seems
      to be similar to that observed after acute exposure, and the hemopoiesis recovery
      starts just at the time of irradiation. In evaluating the damage and recovery
      extent after accidental irradiation, we consider it expedient to complement the
      biological dosimetry with the indices studied work including the determination of
      DNA and RNA concentrations in blood of irradiated human beings.

PMID- 1375997
TI  - Compilation of small RNA sequences.
AB  - This is an update containing small RNA sequences published during 1991.
      Approximately two hundred small RNA sequences are available in this and earlier
      compilations. The hard copy print out of this set will be available directly from
      us (inquiries should be addressed to R. Reddy). These files are also available on
      GenBank computer. Sequences from various sources covered in earlier compilations
      (see Reddy, R. Nucl. Acids Res. 16:r71; Reddy, R. and Gupta, S. Nucl Acids Res.
      1990 Supplement, 18:2231 and 1991 Supplement, 19:2073) are not included in this
      update but are listed below.

PMID- 1375996
TI  - A compilation of large subunit (23S- and 23S-like) ribosomal RNA structures.

PMID- 1376000
TI  - [Prognostic factors for postoperative mortality in cancer of the esophagus.
      Analysis of 46 cases].
AB  - Forty six patients with esophageal cancer underwent surgery between January 1986
      and January 1990. In 14 patients (30.4%) distant metastases were recognized
      before surgery, whereas in 29 cases (63%) regional neoplastic lymph node
      infiltration was observed during surgery. Complications during and after surgery
      occurred in 32 (69.6%) patients and in 30 cases (65.2%) respectively. During the
      first 30 days after surgery 12 patients died. This represents a postoperative
      mortality of 26.1%. Among a total number of 51 variables analyzed in this study,
      11 influenced the postoperative mortality: duration of intubation, previous
      history of toxic syndrome, presence of distant metastases before surgery,
      presence of neoplastic node involvement during surgery, tumor size greater than 4
      cm, localization of the tumor at the middle third of the esophagus, respiratory
      insufficiency, cardiac failure, septic shock, and suture failure during the
      postoperative phase. However, multivariate analysis revealed that only three of
      these variables had an independent prognostic value on postoperative mortality:
      tumor size, presence of distant metastases, and development of respiratory
      insufficiency during the postoperative period.

PMID- 1376002
TI  - The neuraminidases of Trypanosoma cruzi and Acanthamoeba castellanii are
      immunologically related.
AB  - We have recently reported the presence of neuraminidase (NA) activity in
      Acanthamoeba castellanii. We now show that the NAs of T. cruzi and A. castellanii
      share cross-reactive determinants using TCN-2, a monoclonal antibody (mAb)
      against the T. cruzi NA and a mouse polyclonal Ab (anti-TR) raised against a
      tandemly repeated dodecapeptide which contains the epitope recognized by TCN-2
      (Prioli et al., submitted). This cross-reactivity was demonstrated by the
      reaction of TCN-2 and anti-TR with A. castellanii parasites using
      immunofluorescence, immunoblotting and ELISA. Inhibition and immunoprecipitation
      of enzyme activity confirmed that the A. castellanii antigen recognized by TCN-2
      was the NA. Immunoprecipitation of [35S] labeled trophozoite lysates showed the
      A. castellanii NA to have a molecular weight of 115 kDa. In addition, immunoblot
      analysis of subcellular fractions obtained by ultracentrifugation showed the A.
      castellanii NA to be associated with the parasite membrane but not with the
      cytosol or cytoskeleton fractions. These results suggest that the TCN-2 epitope,
      contained within a dodecamer tandem repeat unit, is present in T. cruzi and A.
      castellanii NAs.

PMID- 1376001
TI  - [Benzodiazepines in anesthesiology. Mechanism of action and pharmacology (I)].

PMID- 1376004
TI  - [Effects of substance P on the activities of oviductal isthmic smooth muscle in
      rabbits].
AB  - The effect of substance P (SP) on the activities of oviductal isthmic smooth
      muscle in rabbits was studied. Rabbits were divided into estrous, diestrous and
      ovariectomized groups. The results were as follows: (1) SP suppressed the
      activity of the oviductal isthmic smooth muscle in diestrous rabbit (P less than
      0.05). (2) SP did not suppress the activities of the oviductal isthmic smooth
      muscles in estrous and ovariectomized rabbits (P greater than 0.05).

PMID- 1376003
TI  - Association of a 59-kilodalton immunophilin with the glucocorticoid receptor
      complex.
AB  - Immunophilins, a family of proteins that exhibit rotamase (peptidyl-prolyl cis
      trans isomerase) activity in vitro, are expressed in many organisms and most
      tissues. Although some immunophilins can mediate the immunosuppressive actions of
      FK506, rapamycin, and cyclosporin A, the physiological role of the unligated
      proteins is not known. A 59-kilodalton member of the FK506- and rapamycin-binding
      class was found to associate in the absence of these drugs with two heat shock
      proteins (hsp90 and hsp70) and the glucocorticoid receptor (GR). Together, these
      proteins make up the inactive GR, thus biochemically linking two families of
      proteins proposed to be involved in protein folding and assembly as well as two
      potent immunosuppressive modalities.

PMID- 1376005
TI  - [There is no psychiatric care without a caring situation].

PMID- 1376006
TI  - [Guanethidine blockade for palliative treatment in reflex dystrophy].
AB  - Guanethidine blockade was employed in 22 patients with causalgia, hyperpathia and
      reflex dystrophy in an upper limb. Guanethidine was administered by means of
      regional intravenous technique in which 20 mg guanethidine was mixed with 400 IU
      of heparin and 70 mg lignocaine. Avascularity was present for 20 minutes. The
      number of blockades was determined in advance. In 68% of the patients, beneficial
      results occurred as they were relieved of pain or improved considerably.
      Employment of lignocaine in the injection solution made the blockade less
      painful.

PMID- 1376007
TI  - Carcinosarcoma of the prostate.
AB  - A very rare case of carcinosarcoma of the prostate is reported. The patient was a
      77-year-old man in whom both primary and metastatic tumors presented the
      pathology of carcinosarcoma of the prostate. The carcinosarcoma was resistant to
      anti-androgen therapy, and the patient showed low level of serum prostatic acid
      phosphatase and was free from bony metastases despite multiple metastases to the
      lung, liver, pancreas, para-aortic lymph nodes, spleen and penis. The sarcomatous
      component consisted of chondrosarcoma and fibrosarcoma, both of which were
      positive for vimentin. The carcinomatous component was positive for both keratin
      and prostatic acid phosphatase.

PMID- 1376009
TI  - Glycolipid expression in prostatic tissue and analysis of the antigen recognized
      by antiprostatic monoclonal antibody APG1.
AB  - The expression patterns of glycolipid from prostatic hyperplasia, prostatic
      cancer and normal prostate tissue were observed. A further analysis of antigen
      recognized by mouse monoclonal antibody APG1, which was gained by immunizing
      glycolipids extracted from human prostate cancer, was also performed. In cancer
      tissue, both of the lactosyl and globoside series glycolipids were found to be
      generally reduced, although in the ganglioside series, GM3 and GD3 were not
      reduced and only the glycolipids with longer chains than GD2 were found to be
      reduced. These results indicated that the inhibition of sugar chain elongation,
      but not sialylation, was the main synthetic change occurring with carcinogenesis
      of the human prostate. APG1 reacted with only two bands near GM2 and GD2 of the
      ganglioside fraction on a thin-layer chromatography plate, but it did not react
      with any of the known gangliosides of the ganglioside series including GM2 and
      GD2. Histochemically, APG1 showed intense reaction only in frozen tissue sections
      of human prostate, and the reactivity decreased with the increasing grade of
      cancer. Therefore, this antigen was considered to be a prostate-specific and
      differentiated antigen reacting with nonganglioseries gangliosides.

PMID- 1376008
TI  - Behavior of epithelial differentiation antigens (carcinoembryonic antigen,
      epithelial membrane antigen, keratin and cytokeratin) in transitional cell
      carcinomas of the bladder.
AB  - Results of an immunohistochemical study in normal urothelium and transitional
      cell carcinomas of the bladder are presented. Paraffin-embedded material was
      confronted with immunoantisera against carcinoembryonic antigen (CEA), keratin
      (K), cytokeratin (CK) and epithelial membrane antigen (EMA). Immunohistochemical
      findings confirm the changes in reactivity of dysplastic urothelium and carcinoma
      in situ for CEA, CK and EMA, in comparison with normal urothelium. Statistically
      significant differences were also found, depending upon tumor stage, in staining
      of transitional cell carcinomas for K and CK. Expression of CK correlated with
      the tumor differentiation grade: normal urothelium and well-differentiated
      carcinomas showed a specific pattern of immunostaining for the basal cells, this
      pattern being lost in poorly differentiated carcinomas.

PMID- 1376010
TI  - Calcification in human osteoblasts cultured in medium conditioned by the
      prostatic cancer cell line PC-3 and prostatic acid phosphatase.
AB  - A medium that had been conditioned by PC-3 cells stimulated the calcification of
      a human osteoblastic cell line, Tak-10, in a nonmitogenic culture. The
      calcification of the osteoblasts was stimulated maximally at a 25% concentration
      of the conditioned medium. Calcification activity was markedly enhanced by the
      addition of both prostatic acid phosphatase (PAP) and its substrate, alpha
      glycerophosphate, to the medium; however, PAP added alone did not enhance this
      activity. These results suggest that human prostatic carcinoma cells produce a
      factor that stimulates the calcification of the human osteoblasts. Results have
      also suggested that PAP is a requisite for osteogenesis provided that its
      substrates are abundant in the medium.

PMID- 1376011
TI  - Benign prostatic hyperplasia and erectile dysfunction: a review.

PMID- 1376012
TI  - Synthetic recombinant vaccine expressing influenza haemagglutinin epitope in
      Salmonella flagellin leads to partial protection in mice.
AB  - The influenza virus haemagglutinin epitope 91-108, which is a conserved amino
      acid sequence in all type A H3 strains, was expressed in Salmonella flagellin, to
      evaluate its potential as a vaccine. For that purpose, a synthetic
      oligonucleotide comprising 54 bases coding for the corresponding sequence was
      inserted into the plasmid pLS408 and transformed into Escherichia coli JM101.
      Colonies containing the recombinant plasmid were used to transform Salmonella
      typhimurium LB5000 and were then transduced to a flagellin negative 'live
      vaccine' aroA mutant of Salmonella dublin. Rabbits immunized either with the live
      recombinant S. dublin or with the flagellin isolated from it, showed significant
      levels of IgG response against the synthetic peptide 91-108 as well as against
      the intact A/Texas/77 influenza virus. Mice immunized with the same preparations
      developed influenza-specific IgG antibodies in the blood and secreted IgA
      antibodies in their lungs. Furthermore, these mice showed about 50% protection
      against challenge infection with the virus. The most successful results were
      achieved by intranasal immunization with the isolated recombinant flagellin, when
      employed without the aid of adjuvant.

PMID- 1376013
TI  - Vascular remodeling after laser photocoagulation: concurrent regeneration and
      atrophy.
AB  - Laser photocoagulation is associated with paradoxical results: it causes
      obliteration of vessels, but leads also to the formation of new ones. In an
      attempt to better understand this dual vascular response we conducted an
      ultrastructure study of the choroidal vascular repair following krypton laser
      injury in rats. Three processes were observed: recanalization,
      neovascularization, and atrophy of both recanalized and newly formed capillaries.
      Post-lasering repair of the choroidal vasculature can therefore be described as a
      remodeling process, characterized by both regeneration and involution. The latter
      appears to be a secondary process of atrophy, contributing to permanent vascular
      obliteration. These mechanisms might explain why, in spite of initial vascular
      regeneration, laser photocoagulation treatment has a beneficial effect on
      choroidal subretinal neovascularization.

PMID- 1376014
TI  - [Effects of trihexyphenidyl on slow action potentials in guinea pig papillary
      muscles].
AB  - Effects of trihexyphenidyl (THP) were examined on the slow action potentials
      (SAP) induced by isoproterenol (Iso), histamine (His), Bay k 8644 or tetrodotoxin
      (TTX), in guinea pig papillary muscles. THP 10, 50, and 100 mumol.L-1 depressed
      the maximal upstroke velocity (Vmax) and the action potential amplitude (APA) of
      SAP. These effects were reversed partially by the elevation of the concentration
      of calcium from 2.0 to 5.6 mmol.L-1. The results suggest that THP can inhibit
      calcium inflow in myocardium.

PMID- 1376015
TI  - Prediction of N-acetylprocainamide disposition kinetics in rat by combination of
      gamma variate and physiological pharmacokinetic model.
AB  - Clearances and tissue/blood drug concentration ratios of N-acetylprocainamide
      (NAPA) in rats were determined. The clearances of NAPA in rat blood, liver, and
      kidney were 13.1, 4.88, and 8.24 ml.kg-1.min-1, respectively. Disposition
      kinetics of NAPA in rats was predicted with combination of gamma variate and
      physiological pharmacokinetic model. Equation for estimating the concentration of
      NAPA in rat blood following iv NAPA 40 mg.kg-1 was C = 55.06t(-0.220) exp(
      0.00713t). Using r2 value as a criterion, we found a good agreement between
      predicted and observed concentrations in blood, lung, small intestine, heart,
      brain, and skin.

PMID- 1376016
TI  - Genetic determination of exocrine pancreatic function in cystic fibrosis.
AB  - We showed elsewhere that the pancreatic function status of cystic fibrosis (CF)
      patients could be correlated to mutations in the CF transmembrane conductance
      regulator (CFTR) gene. Although the majority of CF mutations--including the most
      common, delta F508--strongly correlated with pancreatic insufficiency (PI),
      approximately 10% of the mutant alleles may confer pancreatic sufficiency (PS).
      To extend this observation, genomic DNA of 538 CF patients with well-documented
      pancreatic function status were analyzed for a series of known mutations in their
      CFTR genes. Only 20 of the 25 mutations tested were found in this population.
      They accounted for 84% of the CF chromosomes, with delta F508 being the most
      frequent (71%), and the other mutations accounted for less than 5% each. A total
      of 30 different, complete genotypes could be determined in 394 (73%) of the
      patients. The data showed that each genotype was associated only with PI or only
      with PS, but not with both. This result is thus consistent with the hypothesis
      that PI and PS in CF are predisposed by the genotype at the CFTR locus; the PS
      phenotype occurs in patients who have one or two mild CFTR mutations, such as
      R117H, R334W, R347P, A455E, and P574H, whereas the PI phenotype occurs in
      patients with two severe alleles, such as delta F508, delta I507, Q493X, G542X,
      R553X, W1282X, 621 + 1G----T, 1717-1G----A, 556delA, 3659delC, I148T, G480C,
      V520F, G551D, and R560T.

PMID- 1376017
TI  - Analysis of four diverse population groups indicates that a subset of cystic
      fibrosis mutations occur in common among Caucasians.
AB  - To determine the nature and frequency of non-delta F508 cystic fibrosis (CF)
      mutations among diverse populations, we have sequenced exons 9-12 and 19-23 of
      the CF transmembrane conductance regulator (CFTR) gene from 128 CF chromosomes
      (39 U.S. Caucasian, 27 African-American, 42 Northern Irish, and 20 Israeli
      chromosomes). These regions were chosen because they encode the two putative ATP
      binding folds of CFTR, domains which appear to have functional significance. In
      addition, CFTR exons 1 and 2 were analyzed in the American patients. Mutations
      were found on 49 of the 128 CF chromosomes. Nineteen different mutations were
      observed; six were novel, while the remaining 13 had been reported previously by
      our group or by other investigators. Six of nine different mutations found in
      African-American patients were unique to that population. However, the vast
      majority of the mutations found in U.S. Caucasians (eight of nine), Northern
      Irish (four of five), and Israelis (three of three) also occurred in other
      Caucasian groups. The preponderance of previously reported mutations in these
      three groups suggested that a subset of the non-delta F508 mutations occur in
      common among Caucasians. A survey of mutation frequencies in other Caucasian
      groups confirmed this observation. Unfortunately, this subset accounts for less
      than half of non-delta F508 CF mutations in most groups. These data suggest that
      screening for delta F508 and this select group of mutations will efficiently and
      economically maximize the number of CF mutations identified in Caucasian groups.
      However, it will be difficult to detect more than 90% of mutant CFTR alleles
      except in ethnically and geographically discrete populations where CF is the
      result of founder effect.

PMID- 1376018
TI  - A molecular defect in human protoporphyria.
AB  - Protoporphyria is generally an autosomal dominant disease that is characterized
      clinically by photosensitivity and hepatobiliary disease and that is
      characterized biochemically by elevated protoporphyrin levels. The enzymatic
      activity of ferrochelatase, which catalyzes the last step in the heme
      biosynthetic pathway, is deficient in all tissues of patients with
      protoporphyria. In this study, sequencing of ferrochelatase cDNAs from a patient
      with protoporphyria revealed a single point mutation in the cDNAs resulting in
      the conversion of a Phe(TTC) to a Ser(TCC) in the carboxy-terminal end of the
      protein, F417S. Further, the human ferrochelatase gene was mapped to chromosome
      18q21.3 by chromosomal in situ suppression hybridization. Finally, expression of
      recombinant ferrochelatase in Escherichia coli demonstrated a marked deficiency
      in activity of the mutant ferrochelatase protein and of mouse-human mutant
      ferrochelatase chimeric proteins. Therefore, a point mutation in the coding
      region of the ferrochelatase gene is the genetic defect in some patients with
      protoporphyria.

PMID- 1376019
TI  - Subretinal fibrosis after laser photocoagulation for diabetic macular edema.
AB  - Seven eyes had subretinal fibrosis after grid laser photocoagulation for diabetic
      macular edema. The fibrosis caused persistent loss in visual acuity, and in six
      of the seven eyes, was not associated with detectable laser-induced Bruch's
      membrane rupture or subretinal hemorrhage. Choroidal neovascularization was
      detected in only one patient, who was notably younger (27 years) than the median
      age of 70 years in this series. The median preoperative visual acuity was 20/80
      (range, 20/40 to 20/400); the median postoperative visual acuity was 20/400
      (range, 20/80 to counting fingers). The subretinal fibrosis was detected at a
      median of three months (range, 14 days to 4 1/2 months) after laser therapy. In
      one of five bilaterally treated patients (20%), subretinal fibrosis developed in
      both eyes. Subretinal fibrosis may be caused by undetected choroidal
      neovascularization or by excessive proliferation after stimulation of an aged
      retinal pigment epithelium. Subretinal fibrosis may be a potential cause of loss
      in visual acuity after laser treatment for diabetic macular edema.

PMID- 1376021
TI  - Multilocular renal cyst. Immunohistochemical and lectin-binding study.
AB  - Multilocular renal cyst is an uncommon lesion of uncertain pathogenesis seen in
      children and adults. We report the immunohistochemical and lectin-binding
      profiles of three MRC occurring in adults. All cases had strong and uniform
      cytoplasmic staining of lining epithelial cells for keratin and binding sites for
      arachis hypogaea lectin, similar to that seen for the distal convoluted tubules
      or collecting ducts in normal kidney. However, we found variable expression of
      other distal nephron markers, including epithelial membrane antigen and Ber-EP4.
      Furthermore, lining cells in some lesions coexpressed proximal nephron markers
      such as alpha-1-antitrypsin and lysozyme, as well as binding sites for lotus
      tetragonolobus lectin. Immunostaining for type IV (basement membrane) collagen
      demonstrated a continuous subepithelial basement membrane zone and basal laminae
      surrounding desmin-positive stromal cells. Areas of active collagen synthesis and
      stromal procollagen deposition were visualized within the interlocular septae
      using a monoclonal antibody to type I procollagen. Significant proliferative
      activity was not detected in the lining epithelium or stroma using the anti
      proliferating cell nuclear antigen. In conclusion, MRC show aberrant tubular
      epithelial glycoprotein and glycoconjugate expression, low proliferative
      activity, and associated activation of interlocular stromal cells.

PMID- 1376020
TI  - Macrophage markers in diagnostic neuropathology.
AB  - It can be difficult to differentiate the cells of infiltrating gliomas from
      macrophages associated with demyelinating lesions or cerebral infarcts,
      especially in tissue with freezing artifact or tissue that is technically
      suboptimal. We therefore sought to identify a reliable immunohistochemical marker
      for central nervous system macrophages that could be used on routinely processed
      tissue. The reactions of commercially available markers [Ham-56, Mac 387, CD68,
      CR3/43, DR alpha, lysozyme, CD16, and Ricinus communis agglutinin-1 (RCA-1)] were
      studied in normal cerebellum, subacute infarcts, viral encephalitis with
      microglial nodules, radiation necrosis, Alzheimer's disease, medulloblastoma, T
      cell lymphoma, oligodendroglioma, gliomatosis cerebri, and microgliomatosis
      cerebri. We also performed a more extensive investigation of Ham-56 with largely
      surgical material. We concluded that (a) RCA-1 is a sensitive marker for
      microglia, either resting or responding to injury, but staining must be
      interpreted carefully because endothelial cells and reactive astrocytes
      frequently stain as well. This marker was useful in highlighting focal
      inflammation in HIV encephalitis. (b) CD68 is a specific marker for resting
      microglia. A case of microgliomatosis cerebri was intensely stained. (c) Ham-56
      is a sensitive, specific (with the exception of endothelial cells), and reliable
      marker of central nervous system macrophages in routinely processed autopsy and
      surgical material. It is especially useful in distinguishing the macrophages in
      demyelinating disease and cerebral infarcts from neoplastic glial cells.

PMID- 1376022
TI  - Argyrophilia and granin (chromogranin/secretogranin) expression in female breast
      carcinomas. Their relationship to survival and other disease parameters.
AB  - Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a
      series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and
      1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of
      these argyrophilic tumors showed the presence, either throughout the whole tumor
      mass (pure form) or in some areas (mixed form), of distinctive though not
      pathognomonic cellular features. Immunocytochemistry revealed the presence of
      chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of
      these argyrophilic carcinomas and of neuron-specific enolase (NSE)
      immunoreactivity in all of them. The three neuroendocrine markers were also
      immunolocalized at the ultrastructural level in the dense-core granules (granins)
      and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the
      chromogranin A and B and NSE immunoreactivities and documented the presence of
      secretogranin II. We also studied the relation of the histologic, histochemical,
      and immunocytochemical features to prognosis. There was no significant
      correlation between argyrophilia and such clinical parameters as age, menopausal
      status, tumor size, and overall survival; however, the pure form of argyrophilic
      tumors had a significant association with less frequent lymph node involvement
      and a low histologic grade.

PMID- 1376023
TI  - Epithelioid hemangioendothelioma of the brain.
AB  - Epithelioid hemangioendothelioma is a recently described vascular neoplasm
      characterized by epithelioid tumor cells and borderline biologic behavior. Its
      four principal sites of occurrence are the soft tissue, liver, lung, and bone. We
      report a case of primary cerebral epithelioid hemangioendothelioma in a 4-month
      old male infant. The tumor consisted of loose aggregates of epithelioid cells
      with a focal cordlike or bridging-branching pattern, supported in a fibromyxoid
      stroma. The tumor cells displayed frequent intracytoplasmic vacuoles.
      Immunohistochemically, the tumor cells showed positive staining for Ulex
      europaeus agglutinin, vimentin, and cytokeratin. The tumor pursued an indolent
      clinical course. The patient was alive 28 months after initial presentation, but
      he was left with a severe neurological deficit because of the location and growth
      of the tumor.

PMID- 1376024
TI  - Designing legible slides for national meetings.

PMID- 1376025
TI  - CD5 B Cells in Development and Disease. Proceedings of a conference. June 3-6,
      1991, Palm Beach Gardens, Florida.

PMID- 1376026
TI  - Layered evolution in the immune system. A model for the ontogeny and development
      of multiple lymphocyte lineages.

PMID- 1376027
TI  - The fetal omentum in mice and humans. A site enriched for precursors of CD5 B
      cells early in development.
AB  - From these studies the fetal omentum appears to be an important site of B-cell
      generation in humans and a source of CD5 B cells in mice. We have analyzed the
      fetal omentum in other species and have found that B-cell development as
      determined by the presence of cytoplasmic IgM+ pre-B cells is also detected in
      the fetal rabbit omentum. We do not know if there is bias towards the production
      of CD5 B cells in this species; however, these preliminary results demonstrate
      that this site may be conserved throughout evolution in mammals as a site of B
      cell generation. Because the fetal liver is also a source of precursors that can
      reconstitute this B-cell subset, what is the relationship between omentum and
      liver during the development of Ly-1 B cells? The most obvious relationship
      between these two sites is that cells simply migrate from one location to the
      other; that is, precursor cells may migrate from the fetal liver into the fetal
      omentum and in this milieu give rise to exclusively Ly-1+ B cells or the sister
      population. Alternatively, precursors of Ly-1 B cells may arise in the omentum
      and migrate to the liver. This is demonstrated graphically in the diagram (Fig.
      6a) of a transverse section through an 8-week human fetus. In this paper,
      however, we suggest a model for the development of Ly-1+ B cells from the omentum
      and liver in which Ly-1 B cells arise from distinct precursors located in situ in
      the mesodermally derived omentum and mesothelial-derived liver capsule. The
      omentum primordia forms as the back to back fusion of the mesodermally derived
      lining of the peritoneal cavity, and this lining surrounds the developing gut
      when the liver begins to develop as an outgrowth of the intestinal primordia at
      approximately 3.5 weeks gestation; the outer covering or capsule of the liver is
      derived from the same tissue of origin as the omentum. Figure 6B is a diagram of
      a section through the same plane as Figure 6A but the body wall has been omitted.
      We propose that the Ly-1+ B cells arise in situ in the omentum and lining of the
      liver as indicated in Figure 6B. That Ly-1+ B cells arise from distinct
      precursors has been suggested by others, but ours is the first evidence for a
      developmental site that apparently contains B-cell progenitors for this B-cell
      subset.

PMID- 1376028
TI  - Loss of CD23 is a consequence of B-cell activation. Implications for the analysis
      of B-cell lineages.
AB  - When splenic CD5- B cells are stimulated with antiimmunoglobulin they become CD5+
      and have a prolonged in vitro life. Further treatment with IL-6 induces a loss of
      surface CD23 and IgD; that is, they resemble freshly isolated peritoneal CD5+
      cells. These data suggest that the CD5 phenotype is induced after sIg-mediated B
      cell activation. Additional support for this view arises from the observation
      that the loss of CD23 and IgD can be induced by another activation inducer, LPS,
      although in this case CD5 is not expressed. Thus, activation by anti-Ig plus IL-6
      or by LPS induces CD23 loss. Consistent with the hypothesis that the loss of CD23
      is a consequence of activation, we now report that the surface expression of CD23
      varies inversely with the amount of total cellular RNA. We also find both CD23
      positive and negative B cells among freshly isolated splenic CD5- B cells. In
      young mice a proportion of small splenic CD5+ B cells are CD23+, providing
      additional evidence that CD23 is present on all B cells prior to activation. A
      comparison of the features of CD5+ B cells and the antibody responses to thymus
      dependent and thymus-independent antigens leads us to hypothesize that the CD5
      phenotype arises as a consequence of thymus-independent type 2 (TI-2)
      stimulation. The relationship of CD5 expression to B-cell lineage (fetal vs.
      adult bone marrow) is discussed.

PMID- 1376029
TI  - Isotype switching in CD5 B cells.

PMID- 1376031
TI  - Antigen presentation after macrophage lineage switch of CD5 pre-B cells.

PMID- 1376030
TI  - IFN-tau induces CD5+ lymphoma B-cell line 29M10 to differentiate to IgG1-bearing
      cells and to secrete IgG1 isotype.

PMID- 1376032
TI  - CD5 B cells in the rat?

PMID- 1376033
TI  - Detection of CD5 B cells in Peyer's patches of mice.

PMID- 1376034
TI  - Adoptive transfer of murine B-cell lineages.

PMID- 1376035
TI  - Ly-1 B-lineage cells downregulate the number and proliferation of B-cell
      precursors.

PMID- 1376036
TI  - Reconstitution of xid mice with donor cells enriched for CD5+ B cells restores
      contrasuppression.

PMID- 1376037
TI  - CD5-like phorbol-ester responsiveness in conventional B cells activated through
      surface immunoglobulin.

PMID- 1376038
TI  - Xid mice lack regulatory immunoglobulin, which contributes to the enhancement of
      SRBC responses.

PMID- 1376039
TI  - IL-10 production by CD5 B cells.

PMID- 1376040
TI  - Cytokines mediating the proliferation and differentiation of B-1 lymphocytes and
      their role in ontogeny and phylogeny.

PMID- 1376041
TI  - Lymphokine production by B cells from normal and HIV-infected individuals.
AB  - Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are both
      secreted by in vivo-activated normal B cells and by in vivo-activated B cells
      from patients with polyclonal B-cell activation, including individuals infected
      with the human immunodeficiency virus (HIV). Furthermore, IL-6 and TNF-alpha are
      involved in autocrine and paracrine regulation of human B-cell differentiation.
      Following in vitro stimulation of normal B cells with Staphylococcus aureus Cowan
      strain I and IL-2, there is a rapid but brief increase in supernatant levels of
      TNF-alpha. There is also an initial increase followed by a subsequent and more
      sustained increase in IL-6 production. The secondary rise in IL-6 production is
      dependent upon the prior production of TNF-alpha. There is no significant
      difference in IL-6 and TNF-alpha secretion by CD5 positive versus CD5 negative
      tonsillar B cells. Ig production by normal in vitro-activated B cells and freshly
      isolated B cells from patients with hypergammaglobulinemia is largely dependent
      upon TNF-alpha and IL-6 production. As another measure of B-cell TNF-alpha and IL
      6 production, freshly isolated B cells from HIV-infected individuals induce virus
      production by chronically HIV-infected cells in which HIV production is known to
      be triggered by a variety of cytokines. By contrast, freshly isolated B cells
      from normal controls fail to increase HIV production unless they are stimulated
      in vitro. Thus, the spontaneous production of IL-6 and TNF-alpha by B cells from
      individuals infected with HIV may contribute to viral expression as well as to
      the hypergammaglobulinemia often associated with HIV infection.

PMID- 1376042
TI  - Signaling to a CD5+ B-cell clone through surface Ig and MHC class II molecules.
AB  - Cells of the CD5+ mouse B-cell clone CH12.LX are induced to become antibody
      secreting cells by costimulatory signals delivered by binding of their surface Ig
      and MHC class II molecules. Class II-mediated signals can be delivered by the
      binding of either T cells or class II-specific monoclonal antibodies. Divalent,
      but not monovalent antigen-binding fragments of mAbs are effective in signalling,
      and cross-linking intact anti-class II mAbs with isotype-specific Ab enhance
      class II-mediated signaling. Class II-mediated signaling is accompanied by a rise
      in cAMP and is blocked by an adenyl cyclase inhibitor. The cAMP analogue
      dibutyryl cAMP, can partially but not completely substitute for the class II
      mediated signal. The costimulatory Ig-mediated signal can be delivered by binding
      of either antigen or antiidiotype Ab, but anti-IgM Abs are much less effective.
      Antibodies specific for Ig constant regions are much more effective, however, if
      they engage both the mIgM and mIgD molecules; anti-kappa Abs or a combination of
      anti-IgM and anti-IgD Abs were more effective in signaling.

PMID- 1376043
TI  - Cytokine receptors on Ly-1 B cells. IL-5 and its receptor system.

PMID- 1376044
TI  - CD5 expression is modulated as the B cell moves through the cell cycle.

PMID- 1376045
TI  - Coexpression of CD5 and IL-5 receptor on peritoneal B cells.

PMID- 1376046
TI  - Multiple IL-10 antibody treatment blocks the development of Ly-1 lineage B cells.

PMID- 1376047
TI  - Gene expression of two putative signaling molecules in murine CLL-like CD5+B
      cells.

PMID- 1376048
TI  - Synergy between TGF-beta and anti-IgM in growth inhibition of CD5+ B-cell
      lymphomas.

PMID- 1376049
TI  - VH12 rearrangements in adult peritoneal B cells.
AB  - About half of the phosphatidylcholine (PtC)-binding peritoneal B cells of B10.H
      2aH-4bp/Wts mice express the VH12 gene. In these cells the D-region gene segments
      are restricted in length and sequence and are always rearranged to JH1,
      suggesting that PtC-specific B cells are clonally selected. To assess the extent
      to which this VH gene is used by peritoneal B cells to encode antibodies of other
      specificities, we have analyzed the length and sequence of D-region gene segments
      of VH12-D-JH1 rearrangements in peritoneal B cells independent of antigen
      specificity by PCR. We find that all 34 randomly chosen VH12-D-JH1 rearrangements
      analyzed are productive and have D regions that are restricted identically to
      those of PtC-specific B cells. These data suggest that essentially the entire
      repertoire of VH12-D-JH1 rearrangements are used by B cells that bind PtC,
      further illustrating the degree to which this repertoire is shaped by antigen
      selection.

PMID- 1376050
TI  - Perinatally derived antiidiotypic antibodies from the antipolyfructosan immune
      response. Molecular analysis of idiotype regulation.

PMID- 1376051
TI  - Somatic mutations in the VH genes of high-affinity antibodies to self and foreign
      antigens produced by human CD5+ and CD5- B lymphocytes.

PMID- 1376052
TI  - T cell-dependent antibody production by Ly-1 B cells.
AB  - Through the use of a SCID transfer system, we have demonstrated that under
      certain conditions, the production of Ig by Ly-1 B cells can be modulated by T
      cells. This modulation can take the form of enhanced isotype production or
      isotype-switch induction and to some extent appears to be dependent on the
      activation state of the T cells. Furthermore we have shown that Ly-1 B cells can
      mount an idiotypically restricted T cell-dependent immune response to the antigen
      PC-KLH. This result suggests that the previous failure to observe T cell
      dependent responses by Ly-1 B cells has been due to these B cells being "blind"
      to the antigens used and is not due to some inherent property of these B cells.
      When one considers the previous reports of the substantial contribution of Ly-1 B
      cells to the natural serum immunoglobulin levels and the ability of T cells to
      affect Ig production by Ly-1 B cells documented in this report, it is clear that
      the interaction of T cells with the Ly-1 B-cell population is important in
      determining the "natural" serum Ig repertoire of the mouse.

PMID- 1376053
TI  - Characteristics and development of the murine B-1b (Ly-1 B sister) cell
      population.
AB  - In this paper we have outlined the evidence for two distinct branches of the B-1
      cell lineage. The data show that phenotypically B-1a and B-1b cells are
      essentially identical, distinguished only by the presence or absence of the CD5
      antigen. Functionally no differences between the two populations have yet been
      identified. Both produce anti-PtC antibodies, a specificity not observed in
      conventional B cells. Both produced high levels of IgM as measured in adoptive
      transfer experiments. Developmentally, B-1a and B-1b cells are indistinguishable
      with respect to generation from progenitors present in fetal liver and omentum,
      feedback regulation of new B-1a and B-1b cells from bone marrow, self
      replenishment from Ig+ cells following adoptive transfer, and the generation of
      clonal populations. The major difference in the two populations is seen in the
      development of B-1a and B-1b cells from B220- progenitors in the adult bone
      marrow. Although B220- B-1a progenitors are rare in adult (greater than 6 weeks)
      bone marrow, the progenitors for B-1b cells persist well into adulthood. Our
      understanding of B-1b cell ontogeny is at a stage similar to that of B-1a cells
      five years ago. We have evidence from transfer experiments that strongly suggests
      the existence of two distinct progenitors for B-1a and B-1b, but we have yet to
      physically separate these progenitors as Solvansen et al. have done for B-1 and
      conventional B cells. Furthermore we must determine whether the B-1b cells that
      develop from fetal liver and bone marrow are functionally and developmentally
      equivalent to those that develop from adult bone marrow. As with B-1a cells, the
      role of B-1b cells in the immune system is unclear. Although we have not yet
      discerned functional differences between B-1a and B-1b, given the recent
      identification of CD72 (Lyb-2) as the ligand for CD5, it is tempting to speculate
      that B-1a cells are more involved in B-B cell interactions such as idiotype-anti
      idiotype regulation of the early B-cell repertoire and that B-1b cells are more
      involved in B-T cell interactions. Whatever their function, it is clear that in
      trying to understand the role of the B-1 lineage it is important to consider both
      the B-1a and B-1b lineages.

PMID- 1376054
TI  - Selection of autoantibody specificities in the Ly-1 B subset.

PMID- 1376055
TI  - Analysis of immunoglobulin from hybridomas obtained by fusing spontaneously
      arising CD5+ B-cell clones.

PMID- 1376057
TI  - Autoantibody-mediated regulation of tumor growth.

PMID- 1376056
TI  - Immunoglobulin V gene expression in CD5 B-cell malignancies.
AB  - Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphomas (SLL)
      generally are malignancies of CD5 B cells. Immunophenotypic and clinicopathologic
      data, however, are required to distinguish subtypes that apparently have a
      different cytogenesis than that of conventional CLL or SLL. In addition to
      expressing CD5, neoplastic cells of the latter are also distinctive in that they
      frequently coexpress surface immunoglobulin (Ig), bearing one or more cross
      reactive idiotypes (CRIs) (e.g. 17.109, G6,) that commonly are found on
      monoclonal IgM autoantibodies. The frequent occurrence of such CRIs reflects both
      the biased rearrangement and subsequent selected expression of Ig V genes with
      little or no somatic mutation. IgM/L CLL, for example, frequently (8/33) harbor
      abortive Ig rearrangements involving Humkv325, the VK gene encoding the 17.109
      CRI. Also, the VH1 gene(s) encoding the G6 CRI accounts for over 10% of all VH
      genes and over 60% of all the VH1 genes used in randomly selected common CLL/SLL.
      Furthermore, comparison with the Ig expressed by nonmalignant G6 CRI+ B cells
      reveals an apparent restriction in the CDR3 of IgH expressed by G6 CRI+ CLL.
      Coupled with the observed potential bias in antibody light chain and heavy chain
      pairing in B-CLL, these data suggest that the autoantibodies expressed in this
      disease are selected based on antigen-binding activity. Collectively, our studies
      indicate that nonstochastic Ig V gene rearrangement and subsequent selection may
      influence the Ig repertoire expressed in this common B-cell malignancy.

PMID- 1376058
TI  - Large-cell "mixed-phenotype" lymphoma in AIDS. Identification of a CD5-expressing
      subset of B-cell non-Hodgkin's lymphoma.
AB  - We have characterized cells from an AIDS-associated non-Hodgkin's lymphoma (NHL).
      We found a malignant CD5+ B cell (approximately three-fourths of cells), with the
      balance of cells comprised of T cells having an activated phenotype. The lymphoma
      was unusual, in that all cells bear "T-lineage" markers, CD3 and CD5, and "B
      lineage" markers, CD19 and CD20. Thus, conventional immunohistologic techniques
      were insufficient to type this mixture of cells; single-cell analysis was
      required. These "mixed-phenotype" lymphomas may occur frequently in AIDS
      associated NHL. Our results show striking similarity to those obtained in the
      analysis of certain murine CD5+ B-cell lymphomas, suggesting that the study of
      lymphomagenesis in the mouse may aid in the understanding of AIDS-associated NHL.

PMID- 1376059
TI  - Coelomic and bone marrow-derived B cells. Developmental constraints versus
      antigen-specific selection.

PMID- 1376060
TI  - Location and function of B-cell lineages.

PMID- 1376061
TI  - The T/B cell antigen, CD5, and the B-cell surface protein, CD72, form a pair of
      interacting receptors.

PMID- 1376063
TI  - CD5 positive and negative B-CLL. Evidence supporting phenotypic heterogeneity in
      B-chronic lymphocytic leukemia (B-CLL).

PMID- 1376062
TI  - Glutathione and immunophenotypes of T and B lymphocytes in HIV-infected
      individuals.

PMID- 1376064
TI  - Biased usage of variable and constant-region Ig genes by IgG+, CD5+ human
      leukemic B cells.

PMID- 1376065
TI  - CD20 and CD5 expression in B-chronic lymphocytic leukemia.
AB  - In order to quantitate a previously noted decrease in CD20 fluorescence intensity
      (FI) on B-CLL lymphocytes, binding capacities [BC x 10(3) +/- 1SD = number of
      antibodies bound per cell] were calculated. The mean (N = 5) BC x 10(3) +/- 1SD
      of CD20 reagents for normal B-PBL and B-CLL lymphocytes confirmed this
      observation. B-PBL and B-CLL were 56 +/- 11 and 61 +/- 14, and 19 +/- 15 and 18
      +/- 16, respectively, for Leu 16 and B1. Although adequate compensation standards
      for the determination of CD5 and CD20 coexpression are not available,
      qualitatively, the density of CD5 on both normal B-PBL and B-CLL is less compared
      to the expression of CD5 by normal T cells. CD5 expression on B-CLL seems to be
      linked to the lower levels of CD20, whereas CD5 expression may appear to be
      absent on CLL lymphocytes expressing normal levels of CD20. Levels of CD20 in B
      CLL suggest involvement of one or two genes (alleles) whose decreased expression
      may be linked to CD5 expression.

PMID- 1376066
TI  - Association of bone marrow growth pattern, coexpression of CD14, and B-cell CD5
      antigen density in 45 B-chronic lymphocytic leukemia (B-CLL) patients.

PMID- 1376067
TI  - Abnormalities in immunoregulatory CD5+ B cells precede the diagnosis of multiple
      myeloma.

PMID- 1376068
TI  - Immunoregulatory capability of murine CLL-like CD5+ B cells.
AB  - NZB mice spontaneously develop clones of hyperdiploid CD5+B cells, which are much
      like the malignant cells of CLL. We have found that these clonal CD5+B cells are
      immunoregulatory. The development of these cells is accompanied by the loss of
      detectable normal percentages of IgM+ B220(6B2)+ B cells secondary to hyperplasia
      of splenic non-B cells, which are positively regulated by the hyperdiploid B-cell
      clone.

PMID- 1376070
TI  - Surface and molecular expression of complement-receptor type 2 of neoplastic CD5+
      B cells in chronic lymphocytic leukemia.

PMID- 1376069
TI  - The IgA receptors of T560, a murine IL-4-secreting, CD5-, IgG2A kappa+, BrMRBC
      binding B lymphoma.

PMID- 1376072
TI  - Genetic regulation of CD5+ B cells in autoimmune disease and in chronic
      lymphocytic leukemia.
AB  - CD5+ B cells have attracted much attention, because of their involvement in both
      autoimmunity and B cell-type chronic lymphocytic leukemia (B-CLL). B-CLL is a
      type of leukemia most often occurring among close relatives and is partly
      associated with the major histocompatibility complex (MHC), a finding relevant to
      autoimmune disease. We established MHC (H-2)-congenic NZB x NZW (NZB/W) F1 mice
      (H-2d/z, H-2z/z, and H-2d/d), in that only H-2d/z heterozygotes developed severe
      SLE, associated with IgG anti-DNA antibodies, as the animals aged. Such age
      associated changes occurred in parallel with the decrease in the splenic, but not
      peritoneal, CD5+ B cells. By contrast, H-2z/z homozygotes did not develop SLE
      but, in turn, a marked clonal proliferation of CD5+ B cells resembling B-CLL did
      occur. H-2d/d homozygotes also did not develop the typical SLE, and a moderate
      CD5+ B frequency persisted. Despite the finding that all the three H-2-congenic
      NZB/W F1 strains produced IgM anti-DNA antibodies, only the H-2d/z heterozygotes
      produced IgG antibodies. Whereas the surface phenotype of major IgM producers was
      CD5+ sIgM+, that of IgG producers was CD5-sIgM-. Genetic and cellular analyses
      supported our thesis that in the heterozygotes IgM to IgG isotype switching
      probably emerges in CD5+ B cells and that this event is associated with the loss
      of CD5 molecules. Because of the lack of genetic elements required for
      differentiation, only signals for proliferation would be functioning in CD5+ B
      cells in the H-2z/z homozygotes. These observations infer that certain different,
      but related, MHC haplotypes may predispose either to B-CLL or to autoimmune
      disease in close relatives.

PMID- 1376071
TI  - Characterization of expanded populations of peritoneal CD5 B cells specific for
      phosphatidyl choline in old B10.H-2aH-4bp/Wts mice.

PMID- 1376073
TI  - Specificity and idiotope expression of IgM produced by CD5+ and CD5- cord blood B
      cell clones.
AB  - Epstein-Barr virus (EBV)-immortalized monoclonal B-cell lines were established
      from CD5+ and CD5- cord-blood B cells. IgM from many of both CD5+ and CD5- clones
      reacted with IgG-Fc, ssDNA, and a variety of other autoantigens. More CD5+ B
      cells that used light chains of the kappa isotype reacted with IgG-Fc and ssDNA
      than kappa-bearing CD5- B cells. Because many of the clones reacted with IgG-Fc,
      they were analyzed for the expression of cross-reactive idiotypes (CRI)
      associated with rheumatoid factor and cold agglutinin paraproteins using murine
      antibodies (mAb) recognizing V kappa and VH subgroup-associated determinants.
      Expression of the V kappa IIIb sub-subgroup-associated idiotope recognized by
      17.109 mAb was expressed at significantly higher frequency (32%; p less than
      0.05) and IgM antibodies derived from the CD5+ compared with the CD5- clones
      (5%). Both CD5+ and CD5- clones expressed the RF paraprotein-associated idiotope
      recognized by G8 mAb to the same extent. Similar results were obtained using
      binding to SpA as a marker of VH III family usage. Furthermore, no differences in
      frequency of expression of RF paraprotein-associated idiotopes recognized by B6
      and/or D12, and characteristic of some antibodies using VH III family genes, were
      found between the CD5+ and CD5- populations. Although a higher than expected
      frequency of VH IV-gene expression was demonstrated (around 30%) in both CD5+ and
      CD5- cells, there were differences in expression of CRI recognized by mAb Lc1 and
      R2.1A2 with specificities for two VH IV subfamilies. While some CD5+ and CD5-
      clones were identified in which their IgM reacted with mAb Lc1, only CD5+ clones
      were recognized by another mAb R2.1A2. Analysis of the relationships between
      antigen specificities and V kappa- and VH-family gene usage indicated that auto-
      or polyreactivity was not associated with V kappa III nor any particular VH
      family. The higher frequency of the V kappa IIIb sub-subgroup-associated idiotope
      recognized by 17-109 in the CD5+ clones and the association of CD5+ B cells with
      the VH IV subfamily recognized by mAb R2.1A2 and 9G4 may suggest that CD5+ B
      cells in cord blood are expanded as a result of recruitment within the fetal
      environment.

PMID- 1376074
TI  - CD5+B in rheumatoid arthritis.

PMID- 1376076
TI  - CD5 B cells. Potential role in the (auto)immune responses to Trypanosoma cruzi
      infection.

PMID- 1376075
TI  - CD5 B cells in autoimmunity.

PMID- 1376077
TI  - CD5+ B lymphocytes and T-cell subsets in a case of juvenile rheumatoid arthritis.
AB  - Recent research has demonstrated that CD5+ B lymphocytes have an important role
      in autoimmune and rheumatic diseases. In a case of juvenile rheumatoid arthritis
      (JRA), we observed the behavior of these cells and other subpopulations of T
      lymphocytes of peripheral blood before and after therapy with thymopentin (TP5).
      All the lymphocyte subpopulations returned to normal range, except the CD5+ B
      cells, where the percentage remained abnormally high (60%). These data suggest
      that CD5+ B cells can be a useful monitoring index and confirm their important
      role in the pathogenesis of juvenile rheumatoid arthritis.

PMID- 1376078
TI  - Do CD5+ B cells secrete antiasialoGM1 antibodies in motor neuron disease?

PMID- 1376079
TI  - CD5+ B cells in normal newborns and infants, and in those with HIV and
      intrauterine infections.

PMID- 1376080
TI  - CD5+ B cells as precursors of CD5- IgG anti-DNA antibody-producing B cells in
      autoimmune-prone NZB/W F1 mice.

PMID- 1376081
TI  - Intraperitoneal injection of CD4+ T cells induces CD5 B cells. Implications for a
      regulatory role of CD5 B cells in experimental autoimmune encephalomyelitis.

PMID- 1376082
TI  - Cytokines in NZB CD5+ B clones.

PMID- 1376083
TI  - Increased immunosuppressive CD5+ B cells in IgA-deficient blood donors.

PMID- 1376084
TI  - CD5+ B cells in myasthenia gravis. Clinical correlations.

PMID- 1376085
TI  - The role of CD5+ B cells in the production of autoantibodies in murine systemic
      lupus erythematosus.

PMID- 1376086
TI  - Analysis of the human CD5- CD45RAlow B-cell subset.

PMID- 1376087
TI  - The relationship between CD5+ and CD5- B cells, immunoglobulin-secreting cells
      (IgSC), and CD4 T cells in human immunodeficiency virus (HIV) infection.

PMID- 1376088
TI  - Comparative evaluation of CD5 B cells in patients with rheumatoid arthritis and
      essential mixed cryoimmunoglobulinemia using FACS analyzer and FACSCAN flow
      cytometer.
AB  - In this study, using both a FACSCAN flow cytometer and the FACS analyzer, and two
      color fluorescence, CD5 B cells have been enumerated in the peripheral blood (PB)
      of normal controls (NC) and patients with rheumatoid arthritis (RA) or essential
      mixed cryoimmunoglobulinemia (EMC). Using a FACSCAN flow cytometer, no
      significant difference was observed between the percentage of CD5 B cells in the
      NC (21.24% +/- 3.71) and RA (24.83% +/- 3.85), or EMC (21.03% +/- 6.38). Using
      the FACS analyzer, however, there was significant difference between the NC
      (9.14% +/- 3.82) and EMC (2.84% +/- 2.58) (p less than 0.05), but no significant
      difference between the NC and RA (7.17% +/- 2.55). Further analysis of 10,000 B
      cells selected by live gating showed that there were three populations of B
      cells, with the majority of B cells unstained, a small number of cells brightly
      stained for CD5 in the NC (3.78% +/- 1.09) or RA (2.80% +/- 0.96), and about
      6.45% to 9.43% with intermediate staining in patients with RA and the NC,
      respectively. In addition, serum low molecular weight IgM (LMW IgM) from patients
      with RA was detected by an enhanced chemiluminescence detection system combined
      with a modified immunoblot technique. A significant linear correlation was
      observed between the percentage of CD5 B cells and the height of LMW IgM peak (r
      = 0.69, p less than 0.05).

PMID- 1376089
TI  - Murine peritoneal Ly-1 B cells do not turn over rapidly.

PMID- 1376090
TI  - Preparative isolation of murine CD5 B cells by panning and magnetic beads.

PMID- 1376091
TI  - Identification and cloning of rabbit CD5.

PMID- 1376092
TI  - Molecular cloning of the rat CD5 gene.

PMID- 1376093
TI  - B-cell subsets defined by the Fc epsilon R.
AB  - The data summarized herein demonstrate the utility of the low-affinity Fc epsilon
      R in delineating murine B-cell subsets. In the peritoneal cavity, the Fc epsilon
      R appears to be a reliable marker in distinguishing between conventional (Fc
      epsilon R+) and Ly-1/sister (Fc epsilon R-) B cells. In the spleens of normal
      animals, flow cytometric and histologic studies established that a distinct
      population of Fc epsilon R- B cells is also present and comprises the marginal
      zones. Thus in the spleen, the Fc epsilon R may be the first murine marker to
      allow for selective purification and analysis of marginal zone B cells. Although
      it is unlikely that splenic Fc epsilon R- B cells are directly related to
      peritoneal Fc epsilon R- Ly-1/sister B cells, further studies will be required to
      address this question. Analysis of autoimmune mice revealed that the splenic Fc
      epsilon R- subset is greatly expanded in these animals and indicates that the Fc
      epsilon R may be a sensitive indicator of abnormalities within the B-cell
      compartment. Additional studies compared the functional capacity of Fc epsilon R+
      and Fc epsilon R- B cells and tested the ability of these populations to isotype
      switch and respond to polyclonal stimuli. The results showed that Fc epsilon R+
      and Fc epsilon R- B cells from both the peritoneum and spleen can switch to
      produce IgG, and all but the peritoneal Fc epsilon R- B cells can switch to the
      IgE class. This latter result is certainly interesting and demonstrates an
      important functional difference between peritoneal and splenic Fc epsilon R- B
      cells. Finally, experiments with B-cell mitogens showed further differences
      between the Fc epsilon R+ and Fc epsilon R- subsets. Whereas Fc epsilon R- B
      cells appeared to be more sensitive to LPS stimulation, Fc epsilon R+ B cells
      were clearly more responsive to an anti-IgM signal. Taken together, the results
      show that the Fc epsilon R is likely to be useful in separating B cells with
      different phenotypic, histologic, and functional characteristics.

PMID- 1376094
TI  - Generation of Ly-1 B cells from developmentally distinct precursors. Enrichment
      by stromal-cell culture or cell sorting.

PMID- 1376095
TI  - The hair cell's mechanoelectrical transducer channel.

PMID- 1376096
TI  - The efferent control of the organs of balance and equilibrium in the toadfish,
      Opsanus tau.
AB  - All vertebrates are endowed with a vestibular efferent system (EVS) consisting of
      somata within the central nervous system with long axons exiting the brain to
      innervate the labyrinth. Behaviorally relevant stimuli related to feeding and/or
      aggressive behaviors and conditions leading to enhanced attentional states or
      alerting activate the EVS. Increased EVS activity modifies the resting rate and
      response dynamics to motion of vestibular afferents. This modification is
      nonuniform across the fiber spectrum of the semicircular canals, for example,
      affecting the more-sensitive, low-spontaneous-activity cells more profoundly than
      their less-sensitive counterparts. The cellular bases for EVS effects are
      excitatory axoaxonic synapses upon primary afferents and axosomatic inhibitory
      synapses upon hair cells.

PMID- 1376097
TI  - Sensory coding in the saccule. Patch clamp study of ionic conductances in
      isolated cells.

PMID- 1376098
TI  - Cholinergic innervation of the cerebellum of the rat by secondary vestibular
      afferents.
AB  - The cholinergic innervation of the cerebellar cortex of the rat was studied by
      immunohistochemical localization of choline acetyltransferase, radiochemical
      measurement of ChAT activity, and double labeling of ChAT-positive neurons with
      HRP injected into the cerebellum. ChAT immunohistochemistry revealed large mossy
      fiber rosettes as well as finely beaded terminals with different morphological
      characterization, laminar distribution within the cerebellar cortex, and regional
      differences within the cerebellum. Large "grapelike" ChAT-positive mossy fiber
      rosettes that were distributed primarily in the granule cell layer were
      concentrated, but not exclusively located, in three separate regions of the
      cerebellum: (1) the uvula-nodulus (lobules 9 and 10); (2) the flocculus, and (3)
      the anterior lobe vermis (lobules 1 and 2). Regional differences in ChAT-positive
      afferent terminations in the cerebellar cortex demonstrated by
      immunohistochemistry were confirmed by regional biochemical measurements of ChAT
      activity. Using ChAT immunohistochemistry in combination with HRP injections into
      the uvula-nodulus, we have studied the origin of the cholinergic projection. The
      caudal medial vestibular nucleus and to a lesser extent the nucleus prepositus
      hypglossus contain ChAT-positive neurons that were double labeled following HRP
      injections into the uvula-nodulus. We conclude that (1) there is a prominent
      cholinergic mossy fiber pathway to the vestibulocerebellum, (2) this pathway
      originates primarily in the caudal third of the medial vestibular nucleus, and
      (3) this cholinergic pathway likely mediates secondary vestibular information
      related to postural adjustment.

PMID- 1376099
TI  - Ionic currents of mammalian vestibular hair cells.

PMID- 1376100
TI  - Some excitatory transmitters in the central vestibular pathways in the gerbil.

PMID- 1376101
TI  - Two-dimensional eye movement and vestibular responses in primate brain stem.

PMID- 1376102
TI  - Tacrolimus (FK 506)--a new therapeutic agent for severe recalcitrant psoriasis.
AB  - BACKGROUND: Psoriasis, a disease of unknown etiology, is in some patients severe,
      extremely debilitating, and unresponsive to conventional therapies, including UV
      B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral
      retinoids, and methotrexate. We report the results from our study of seven
      patients with refractory psoriasis who were treated with the new
      immunosuppressive drug, tacrolimus (FK 506). OBSERVATIONS: All seven patients
      showed a dramatic resolution of psoriasis that remained in remission as long as
      they received full-dose therapy. Serial skin biopsy specimens demonstrated a
      rapid disappearance of the inflammatory infiltrate and a slower resolution of the
      epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of
      observation. Side effects, including nephrotoxicity and hypertension, were
      controlled by appropriate modification of drug dosage. CONCLUSIONS: Tacrolimus, a
      new immunosuppressive agent, is effective in treating patients with severe
      recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but
      it may be related to its ability to modulate immune function. Further studies
      will establish criteria for patient selection and drug dosage, to maximize
      efficacy of this agent in psoriasis, while minimizing its toxicity.

PMID- 1376103
TI  - Frequency of bullous pemphigoid-like antibodies as detected by western immunoblot
      analysis in pruritic dermatoses.
AB  - BACKGROUND AND DESIGN: Ninety-seven patients suffering from a pruritic dermatosis
      were screened for the detection of bullous pemphigoid (BP) antibodies (ab) using
      the Western immunoblot (WB) analysis technique. RESULTS: Twenty-four patients
      (25%) reacted at least twice with the BP antigen on WB analysis at a 1/10
      dilution: seven had typical BP, four had papular BP, 10 had pruritus and prurigo
      of unknown origin, two had eczema, and one had lichen planus. This corresponds to
      13% of BP-type ab in patients who did not fulfill criteria for BP. Therefore, we
      did the following: (1) tested a control group of 24 subjects; (2) assessed the
      reproducibility of the WB method by retesting the same serum samples on different
      epidermal extracts; and (3) estimated the BP ab titer. None of the 24 control
      subjects had detectable BP ab, and reproducible results were obtained in all
      groups when serum samples were retested at the 1/10 dilution. Although 86% (6/7)
      of patients with BP had BP ab titers of 1/100 or greater, only 60% (6/10) of the
      group with pruritus and prurigo and 33% (1/3) of the group with eczema reached
      such titers. CONCLUSION: These results indicate that due to its sensitivity, the
      WB method can detect low titers of BP ab in patients with pruritic dermatoses who
      did not fulfill criteria for BP, and therefore we question the specificity of
      this method.

PMID- 1376104
TI  - A 2-year prospective follow-up study of children and adolescents with disruptive
      behavior disorders. Prediction by cerebrospinal fluid 5-hydroxyindoleacetic acid,
      homovanillic acid, and autonomic measures?
AB  - A 2-year prospective follow-up study of 100% (N = 29) of a sample of children and
      adolescents with disruptive behavior disorders found that the baseline lumbar
      cerebrospinal fluid monoamine metabolite concentration and autonomic nervous
      system activity predicted some subsequent outcomes. The 5-hydroxyindoleacetic
      acid concentration significantly predicted severity of physical aggression during
      follow-up. The skin conductance level significantly predicted
      institutionalization. Correlations were in predicted directions with lower
      cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and autonomic
      activity correlated with poor outcome. Moreover, in multivariate analyses, which
      included nonlaboratory measures as predictors, cerebrospinal fluid and autonomic
      measures still contributed significantly to the prediction. However, hypothesized
      predictions of cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations for
      suicide attempts and of low autonomic nervous system activity for arrests were
      not supported thus far. Patients are still at risk; consequently, these results
      must be considered preliminary. Nonetheless, the results suggest that further
      investigation of relationships between biological factors and outcome of children
      with disruptive behavior disorders is warranted.

PMID- 1376105
TI  - Cerebrospinal fluid monoamine and adrenal correlates of aggression in free
      ranging rhesus monkeys.
AB  - Clinical and preclinical studies involving several different mammalian species
      and research paradigms suggest a negative correlation between aggression and
      central serotonin activity. To test the generalizability of laboratory findings
      in rhesus monkeys that show a negative correlation between cerebrospinal fluid 5
      hydroxyindoleacetic acid concentrations and aggression, we obtained cisternal
      cerebrospinal fluid and blood plasma samples from monkeys living in naturalistic
      conditions. During a semiannual trapping, 28 juvenile and adolescent male rhesus
      monkeys were chosen from a population of 4200 provisioned, free-ranging rhesus
      monkeys living on Morgan Island, a sea island located off the coast of South
      Carolina. Based on direct observations of participation or avoidance of
      aggressive behavior and examinations of apparent fight wounds, 18 monkeys were
      selected for cerebrospinal fluid taps and blood samples. The remaining 10 monkeys
      were selected at random. Descriptions of aggressive behavior and the number of
      old scars and recent wounds were carefully transcribed, and a photograph showing
      wounds and scars was obtained for each animal. Using the transcriptions and
      photographs, researchers experienced in rhesus monkey behavior, but blind to the
      subjects' monoamine and hormone concentrations, were asked to rank the monkeys
      from the most to the least aggressive. The results showed a significant negative
      correlation between high rankings for aggression and cerebrospinal fluid 5
      hydroxyindoleacetic acid concentrations. There was evidence that aggression was
      associated with stress, in that cerebrospinal fluid, norepinephrine, and plasma
      corticotropin and cortisol concentrations were positively correlated with high
      rankings of aggression.

PMID- 1376106
TI  - Relationship between central and peripheral serotonin indexes in depressed and
      suicidal psychiatric inpatients.
AB  - Serious suicidal behavior, affective disorders, and a variety of other
      psychopathologic behaviors and syndromes have been found to correlate with
      measures of the serotonin system. Clinical studies have employed a range of
      serotonin indexes, including the cerebrospinal fluid level of 5
      hydroxyindoleacetic acid, the prolactin response to serotonin agonists, such as
      fenfluramine hydrochloride, and platelet serotonin-related proteins or serotonin
      content. Many of these indexes are correlated with suicidal behavior, but the
      interrelationship of these biologic measures has been uncertain. We studied the
      relationship of a series of serotonin indexes in patients in whom these measures
      were correlated with suicidal behavior. A positive correlation was found between
      cerebrospinal fluid 5-hydroxyindoleacetic acid and the maximal prolactin response
      to fenfluramine but not with platelet serotonin2 receptor indexes. The
      fenfluramine-stimulated maximal prolactin response correlated with platelet
      serotonin2 receptor number, particularly in older patients. We conclude that
      cerebrospinal fluid 5-hydroxyindoleacetic acid measurements cannot be replaced
      but can be complemented by less invasive procedures, such as a fenfluramine
      challenge test or platelet serotonin2 measures, in the study of the relationship
      of the serotonin system to psychiatric disorders.

PMID- 1376107
TI  - Marked reduction in indexes of dopamine metabolism among patients with depression
      who attempt suicide.
AB  - Cerebrospinal fluid studies have reported that low concentrations of the dopamine
      metabolite homovanillic acid are associated with suicidal behavior in depression.
      Although only a small proportion of homovanillic acid in the urine derives from
      the brain, we decided to examine 24-hour urinary outputs of homovanillic acid in
      relation to suicidal behavior in depression. Patients with depression who had
      attempted suicide had significantly smaller urinary outputs of homovanillic acid,
      dihydroxyphenylacetic acid, and total body output of dopamine (sum dopamine) than
      did patients with depression who had not attempted suicide. Patients with
      depression who reattempted suicide during 5-year follow-up had significantly
      smaller urinary outputs of homovanillic acid and sum dopamine than did patients
      who did not reattempt suicide, patients who never attempted suicide, and normal
      control subjects, and had significantly smaller outputs of dihydroxyphenylacetic
      acid than patients who never attempted suicide or control subjects. These data
      suggest that urinary outputs of homovanillic acid may be peripheral correlates of
      suicidality in depression. These data add to data on the low levels of
      homovanillic acid in cerebrospinal fluid in suggesting that diminished
      dopaminergic neurotransmission may play a part in suicidal behavior in
      depression.

PMID- 1376108
TI  - Structural and computational investigations of the conformation of antigenic
      peptide fragments of human polymorphic epithelial mucin.
AB  - Human polymorphic epithelial mucins (PEM) are complex glycoproteins that are
      associated with breast and ovarian carcinomas. The PEM core protein consists of
      variable numbers of a tandem repeat sequence which contains a short antigenic
      hydrophilic region (Pro1-Asp-Thr-Arg-Pro-Ala-Pro7). High-field n.m.r. studies
      undertaken on antigenic 20- and 11-amino acid fragments of the PEM core protein
      in dimethyl sulphoxide have identified a type-I beta-turn to be present in the
      region Pro1-Asp-Thr-Arg4. This region includes and overlaps the identified type-I
      (Asp2-Thr-Arg4) and type-II (Arg4-Pro-Ala6) epitopes of anti-PEM monoclonal
      antibodies. The studies indicate that the beta-turn is stabilized by the presence
      of a salt-bridge interaction between Asp-2 and Arg-4. In order to probe the
      conformations accessible to the PEM peptides a computational study was undertaken
      independently on the peptide Pro-Asp-Thr-Arg-Pro using a modified Metropolis
      Monte Carlo algorithm. This study identified the n.m.r.-observed salt-bridge type
      I beta-turn as the major low-energy conformer. These results suggest that this
      structural motif may be involved in the immune recognition of PEM.

PMID- 1376110
TI  - Human platelet glycoprotein IIIb binds to thrombospondin fragments bearing the C
      terminal region, and/or the type I repeats (CSVTCG motif), but not to the N
      terminal heparin-binding region.
AB  - Major blood membrane platelet glycoprotein IIIb (GPIIIb), also termed GPIV or
      CD365, has been identified as a receptor for thrombospondin (TSP), collagen and
      Plasmodium falciparum-infected erythrocytes. The aim of the present study was to
      identify region(s) of TSP involved in binding of GPIIIb. Proteolytic fragments of
      TSP (M(r) 140 kDa, 120-18 kDa and 27 kDa on SDS/PAGE under reducing conditions)
      were purified by f.p.l.c. and identified by N-terminal gas-phase sequencing,
      e.l.i.s.a. and Western blots using monoclonal antibodies directed against defined
      domains of TSP. The 140 kDa and 120-18 kDa fragments (C-terminal region), but not
      the 27 kDa fragment (N-terminal region), were shown to bind to GPIIIb by using
      e.l.i.s.a. and affinity-chromatography systems. TSP binding to a GPIIIb-affinity
      column was Ca(2+)-dependent and reduced by 45% in the presence of EDTA. Moreover,
      TSP was only partially eluted with EDTA from a Ca(2+)-equilibrated GPIIIb column.
      A fragment of 68 kDa, obtained by further digestion of the 140 kDa fragment,
      bound to the GPIIIb-Sepharose affinity column. This fragment, or stalk-like
      region, bears the TSP type I repeats that show sequence similarity to regions on
      properdin, Plasmodium falciparum proteins and antistasin. Peptides (CSVTCG or
      SVTCGGGV) representing these repeats bound isolated GPIIIb in a Ca(2+)
      independent way, but did not completely inhibit the GPIIIb and TSP interaction.
      These studies indicate that GPIIIb binds to the TSP via the C-terminal region
      and/or the CSVTCG motif, but not to the N-terminal region. Interaction between
      GPIIIb and the TSP C-terminal region or the CSVTCG motif is respectively Ca(2+)
      dependent and -independent.

PMID- 1376109
TI  - Isolation and characterization of a membrane protein from rat erythrocytes which
      inhibits lysis by the membrane attack complex of rat complement.
AB  - The membrane attack complex (MAC) of complement in humans is regulated by several
      membrane-bound proteins; however, no such proteins have so far been described in
      other species. Here we report the isolation and characterization of a rat
      erythrocyte membrane glycoprotein of molecular mass 21 kDa which inserts into
      cell membranes and is a potent inhibitor of the rat MAC. This protein, here
      called rat inhibitory protein (RIP), was first partially purified by column
      chromatography from a butanol extract of rat erythrocyte membranes. Monoclonal
      antibodies (Mabs) were raised against RIP and used for its affinity purification.
      Affinity-purified RIP was shown to inhibit in a dose-dependent manner the cobra
      venom factor (CVF)-mediated 'reactive' lysis of guinea pig erythrocytes by rat
      complement. Conversely, the anti-RIP MAbs 6D1 and TH9 were shown to markedly
      enhance the CVF-mediated lysis of rat erythrocytes by rat complement. RIP acted
      late in the assembly of the MAC (at or after the C5b-8 stage) and was releasable
      from the membranes of rat erythrocytes by phosphatidylinositol-specific
      phospholipase C. These features, together with its size, deglycosylation pattern
      and N-terminal amino acid sequence, lead us to conclude that RIP is the rat
      homologue of the human MAC-inhibitory protein CD59 antigen.

PMID- 1376111
TI  - Molecular biology of the 2-haloacid halidohydrolase IVa from Pseudomonas cepacia
      MBA4.
AB  - The structural gene (hdl IVa) for the Pseudomonas cepacia MBA4 2-haloacid
      halidohydrolase IVa (Hdl IVa) was isolated on a 1.6 kb fragment of Ps. cepacia
      MBA4 chromosomal DNA. The recombinant halidohydrolase was expressed in
      Escherichia coli and Pseudomonas putida and the structural gene was subcloned on
      to the tac expression vector pBTac1. High-level expression from the tac promoter
      was seen to be temperature-dependent, a consequence of the nucleotide sequence
      adjacent to the fragment encoding the halidohydrolase. The nucleotide sequence of
      the fragment encoding the Hdl IVa was determined and analysed. Three ATG codons
      were identified in one of the open reading frames and the one corresponding to
      the start of the hdl IVa structural gene was determined by comparison of the
      predicted amino acid sequences with the experimentally determined N-terminal
      sequences of halidohydrolase IVa. The hdl IVa gene encoded a 231-amino acid
      residue protein of M(r) 25,900. The sequence and predicted structural data are
      discussed and comparison is made with sequence data for other halidohydrolases.

PMID- 1376112
TI  - The antigenicity of the carbohydrate moiety of an insect glycoprotein, honey-bee
      (Apis mellifera) venom phospholipase A2. The role of alpha 1,3-fucosylation of
      the asparagine-bound N-acetylglucosamine.
AB  - A rabbit polyclonal antiserum raised against honey-bee (Apis mellifera) venom
      phospholipase A2 (PLA2) contains antibodies that react exclusively with its
      glycosylated variants and cross-react with plant glycoproteins. The interaction
      of anti-(horseradish peroxidase) antiserum with PLA2 suggests the existence of a
      carbohydrate determinant common to both glycoproteins. E.l.i.s.a. binding and
      inhibition experiments, employing glycoproteins and glycopeptides of plant and
      animal origin with known N-glycan structures, in combination with chemical and
      enzymic deglycosylation, identified alpha 1,3-fucosylation of the asparagine
      bound N-acetylglucosamine as the antigenic determinant. This fucose residue is
      present in the N-glycan of PLA2 and is frequently found in plant glycoproteins,
      whereas mammalian glycoproteins lack this modification.

PMID- 1376113
TI  - Ca2+ transport by digitonin-permeabilized Leishmania donovani. Effects of Ca2+,
      pentamidine and WR-6026 on mitochondrial membrane potential in situ.
AB  - The use of low concentrations of digitonin allowed the quantitative determination
      of the mitochondrial membrane potential of Leishmania donovani promastigotes in
      situ using safranine O. L. donovani mitochondria were able to build up and retain
      a membrane potential of a value comparable with that of mammalian mitochondria.
      The response of promastigotes mitochondrial membrane potential to phosphate,
      carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), valinomycin and Ca2+
      indicates that these mitochondria behave similarly to vertebrate mitochondria
      with regard to the properties of their electrochemical proton gradient. When L.
      donovani promastigotes were permeabilized with digitonin in a reaction medium
      containing MgATP, succinate and 3.5 microM free Ca2+, they lowered the medium
      Ca2+ concentration to the submicromolar level (0.05-0.1 microM). The presence of
      1 microM-FCCP decreased by about 75% the initial rate of Ca2+ sequestration by
      these permeabilized cells. This FCCP-insensitive Ca2+ uptake, probably by the
      endoplasmic reticulum, was completely inhibited by 500 microM-vanadate. On the
      other hand, when vanadate instead of FCCP was present, the initial rate of Ca2+
      accumulation was decreased by about 25% and the Ca2+ set point was increased to
      0.7 microM. The succinate-dependence and FCCP-and Ruthenium Red-sensitivity of
      the Ca2+ uptake detected in the presence of vanadate indicate that this uptake is
      probably by the mitochondria. This interpretation was further supported by the
      Ruthenium Red-sensitive decrease in the mitochondrial membrane potential caused
      by Ca2+ addition. The anti-leishmanial cationic drugs pentamidine and WR-6026
      also induced a rapid collapse of the mitochondrial inner membrane potential of L.
      donovani promastigotes.

PMID- 1376114
TI  - Thrombospondin receptor expression in human neutrophils coincides with the
      release of a subpopulation of specific granules.
AB  - The extracellular matrix (ECM) protein thrombospondin (TSP) binds specifically to
      polymorphonuclear leucocyte (PMN) surface receptors and promotes cell adhesion
      and motility. TSP receptor expression increases 30-fold after activation with the
      synthetic chemotactic peptide, N-formylmethionyl-leucylphenylalanine (FMLP) or
      the Ca2+ ionophore A23187, in combination with cytochalasin B. The expression of
      TSP receptors was correlated with the exocytosis of both specific and azurophil
      granules. Newly expressed TSP receptors are not derived from easily mobilized
      specific granules since agents that trigger some specific granule release
      [phorbol myristate acetate (PMA), FMLP or ionophore A23187 alone] do not increase
      TSP receptor expression. In this study we used the anion-channel blocker, 4,4'-di
      isothiocyanatostilbene-2,2'-disulphonic acid (DIDS) to investigate the source of
      these newly expressed receptors. When PMNs were exposed to cytochalasin B and
      FMLP or to cytochalasin B and ionophore A23187 in the presence of 30-100 microM
      DIDS, TSP receptor expression increased coincidently with vitamin B12-binding
      protein release from specific granules. Under these same conditions, the release
      of the azurophil granule component, myeloperoxidase, was significantly inhibited.
      Using agonists that cause release of specific granules, or both specific granules
      and azurophil granules, we determined that DIDS blocked the release of PMA
      mobilized specific granules and cytochalasin B plus FMLP- or cytochalasin B plus
      ionophore A23187-mobilized myeloperoxidase-containing azurophil granules but not
      specific granules mobilized by cytochalasin B plus FMLP or cytochalasin B plus
      ionophore A23187. These results suggested that PMNs contain at least two
      subpopulations of specific granules: one that is easily mobilized, lacks TSP
      receptors and is inhibitable by DIDS, and one that is difficult to mobilize,
      contains a large pool of TSP receptors and the release of which is enhanced in
      the presence of DIDS.

PMID- 1376116
TI  - Cell cycle progression is associated with distinct patterns of phosphorylation of
      Op18.
AB  - Op18 is a highly conserved major cytosolic phosphoprotein which has been
      implicated in signal transduction in a wide variety of cell types. Freshly
      isolated peripheral blood lymphocytes (PBL) constitutively express low levels of
      mostly unphosphorylated Op18. Following mitogenic stimulation of PBL, Op18
      synthesis is induced at a time when cells are entering S-phase. In this study we
      have characterized Op18 phosphorylation during progression of freshly isolated
      PBL through the cell cycle. Transition from G0 to G1 following activation with
      OKT3 was associated with an increase in a phosphorylated form designated Op18c.
      Progression of cells through G1 into S resulted in an increase in phosphorylated
      Op18 forms, designated Op18a and Op18b, which paralleled new Op18 synthesis.
      Transition of cells into G2 + M resulted in the appearance of the more acidic
      phosphorylated forms Op18d and Op18e. Calphostin C, a specific inhibitor of
      protein kinase C, dramatically decreased all forms of phosphorylated Op18 in OKT3
      treated Jurkat cells. Our results suggest that Op18 phosphorylation is mediated
      in part by PKC activation as well as by other kinases yielding different
      phosphorylated forms at specific stages of the cell cycle.

PMID- 1376117
TI  - Isolation of a human cDNA encoding a 25 kDa FK-506 and rapamycin binding protein.
AB  - Recently, the nearly complete peptide sequence of a 25 kDa rapamycin and FK-506
      binding protein that had been isolated from calf thymus, brain, and spleen was
      reported (1). Based upon the amino acid sequence of this bovine protein, bFKBP25,
      we have isolated from a JURKAT cDNA library the cDNA encoding the human homolog,
      hFKBP25. Translation of the open reading frame contained within this cDNA clone
      yields a sequence that, in its C-terminal half, is 41% identical to the major
      human FK-506 binding protein, hFKBP12, and 43% identical to hFKBP13. The N
      terminal half of hFKBP25 is unrelated to any known protein.

PMID- 1376115
TI  - Formation of salivary-mucosal pellicle: the role of transglutaminase.
AB  - The present investigation was carried out to identify salivary components of
      mucosal pellicles in vivo and explore further the mechanism of interaction
      between salivary molecules and buccal epithelial cells. By using specific
      antisera and immunoprotein blotting, high-(MG1) and low-(MG2) molecular-mass
      salivary mucins, amylase, salivary cystatins and proline-rich proteins were
      detected within mucosal pellicle in vivo. In addition, the data indicated that
      the mucins and proline-rich proteins could be cleaved into lower-molecular-mass
      products, whereas the proline-rich proteins could also be cross-linked into
      higher-molecular-mass complexes. The role of buccal epithelial cell
      transglutaminase in these interactions was further studied by utilizing purified
      iodinated amylase, neutral cystatin SN and acidic proline-rich proteins 1 and 3
      (APRP1 and 3). After incubation with buccal epithelial cells in vitro 125I
      labelled APRPs appeared to undergo a greater degree of cross-linking than 125I
      labelled cystatin SN, as determined by SDS/PAGE/autoradiography. Amylase did not
      appear to be cross-linked at all. Recovery of 125I-labelled APRPs and 125I
      labelled cystatin SN with epithelial cell envelopes after repeated extraction
      suggested that both molecules were cross-linked to envelope proteins, but that
      125I-labelled APRPs were cross-linked to a greater degree than 125I-labelled
      cystatin SN. Cross-linking in buccal epithelial cell preparations was inhibited
      by an excess of methylamine hydrochloride, a transglutaminase substrate. In a
      further assessment of amylase, cystatin and APRPs as transglutaminase substrates,
      only APRP3 and a partially purified preparation of APRPs acted as an amine
      acceptor for the cross-linking of [14C]methylamine by purified transglutaminase,
      as determined by SDS/PAGE/fluorography. This reaction was completely inhibited by
      excess EDTA. The combined data from this study suggest that during mucosal
      pellicle formation multiple components of saliva adsorb to buccal epithelial cell
      surfaces, and that, within this group, selected components are enzymically cross
      linked by an epithelial transglutaminase and/or proteolytically cleaved into
      smaller fragments.

PMID- 1376118
TI  - HIV-1 and HIV-2 reverse transcriptases: a comparative study of sensitivity to
      inhibition by selected natural products.
AB  - One hundred and fifty six pure natural products, which had previously been tested
      against HIV-1 reverse transcriptase, were evaluated for HIV-2 reverse
      transcriptase inhibitory activity. Compounds that lacked effect in the HIV-1
      reverse transcriptase system were found also to be inactive against HIV-2 reverse
      transcriptase. However, compounds belonging to the benzophenanthridine and
      protoberberine classes of alkaloids, certain flavonoids, the iridoid,
      fulvoplumierin, and the ansamycin antibiotic, daunomycin, exhibited similar
      potencies in both enzyme systems. In contrast, HIV-2 reverse transcriptase was
      observed to be four-fold more sensitive toward the inhibitory effects of the
      ipecac alkaloids, O-methylpsychotrine sulfate heptahydrate and psychotrine
      dihydrogen oxalate. Such differences in susceptibilities to inhibitors may
      indicate subtle dissimilarities in enzyme structure and function.

PMID- 1376120
TI  - Further characterization of reversal of signs of induced cotton effects of
      dicumarol derivatives-alpha 1-acid glycoprotein systems by protriptyline.
AB  - The interaction of dicumarol derivatives and protriptyline with respect to the
      binding to alpha 1-acid glycoprotein (AGP) has been investigated by circular
      dichroism (CD), equilibrium dialysis and ultrafiltration. Investigation of the
      induced CD spectra of dicumarol derivatives bound to AGP indicated that the
      conformations of these compounds were different when bound to AGP. Though all the
      dicumarol derivatives, protriptyline and AGP formed a ternary complex,
      interaction modes were different, depending upon the substituent groups at
      position 3 of the dicumarol molecule. On the basis of the protriptyline effect on
      the CD spectra of all dicumarol derivatives bound to AGP, the compounds were
      classified in the following way: (1) Dicumarol, ethylidenebis 4-hydroxycoumarin
      and propylidenebis 4-hydroxycoumarin caused reversal of the sign of ellipticity.
      This interaction was explained by cooperative binding. (2) Butylidenebis 4
      hydroxycoumarin and pentylidenebis 4-hydroxycoumarin generated new band and
      disappeared ellipticity of the original Cotton effect. This interaction was also
      explained by the cooperative binding mode. (3) Ethylbiscoumacetate which
      generated the CD band similar to that of dicumarol in the absence of
      protriptyline, reversed the sign of the CD spectrum only at 325 nm. The
      interaction was anticooperative in nature. (4) Benzylidenebis 4-hydroxycoumarin
      represented type four which had no change in the CD spectrum by the addition of
      protriptyline. This interaction was explained by the two-state model accompanying
      the conformational change of AGP. These results suggested that all compounds,
      except for benzylidenebis 4-hydroxycoumarin, induced negative Cotton effects at
      325 nm by taking the same asymmetrical perturbation by the addition of
      protriptyline and the interaction was carried out according to model 2. An
      attempt to study the interaction mechanism of two or more drugs with regard to
      the binding to protein using these models is thought to help in understanding
      drug-protein interactions.

PMID- 1376119
TI  - High cell density-dependent resistance and P-glycoprotein-mediated multidrug
      resistance in mitoxantrone-selected Chinese hamster cells.
AB  - Mitoxantrone (MIT) resistance has been studied in a colony selected from the CHO
      AA8 parental line in one step under a low degree of selective pressure (9 nM).
      The cells of the clonal isolate AA8/MIT C1(0) were sensitive to 9 nM MIT at low
      cell density but able to grow at high density. Parental AA8 cells were not able
      to grow under the latter condition. Decreased MIT accumulation (-20%) was
      observed at this step (step 0) in the absence of overexpression of mdr RNA coding
      for the drug efflux pump P-glycoprotein. Furthermore, AA8/MIT C1(0) did not
      exhibit cross resistance to vincristine, Adriamycin and etoposide at low cell
      density. During subsequent controlled growth for 2 months at high cell density in
      the presence of 9 nM drug, an additional selection occurred leading to a 4-fold
      MIT-resistant subline AA8/MIT C1(+). This subline was characterized at this step
      (step I) and after an additional 4 months of culture in the presence of 9 nM MIT
      (step II). Analysis of mdr gene expression and gene copy number showed an
      increase in mdr RNA and a pattern of mdr gene amplification which changed between
      step I and II. AA8/MIT C1(+)II exhibited a classical multidrug resistance
      phenotype with decreased accumulation of [14C]MIT and cross-resistance to
      vincristine, Adriamycin and etoposide. The ability to form the cleavable complex
      in the presence of etoposide in DNA topoisomerase II-containing nuclear extracts
      was identical in AA8/MIT C1(+)II and AA8 cell lines. These results demonstrate a
      new sequence of events in MIT resistance: low level of drug resistance at high
      cell density followed by mdr gene amplification.

PMID- 1376121
TI  - CD7- T cells in rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is characterized by decreased expression of
      CD7 in the peripheral blood and in the synovium. The present study was designed
      to identify the basis for and functional consequences of this decreased
      expression. METHODS: Peripheral blood lymphocytes from normal controls and from
      patients with RA or systemic lupus erythematosus (SLE), and T cell lines derived
      from rheumatoid synovium, were evaluated using 3-color fluorescence-activated
      cell sorter analysis. RESULTS: Normal subjects and most SLE patients expressed
      homogeneous, bright CD7 on CD4+, CD45RA+ cells, whereas RA patients demonstrated
      a significantly increased proportion of CD7- cells. T cell lines derived from
      rheumatoid synovium demonstrated a striking deficiency of CD7 on CD4+, CD45RA-
      cells. CD4+, CD45RA+ cells from RA patients changed phenotype after in vitro
      activation to CD45RA negativity, with up-regulation of CD7. CD7-, CD4+, CD45RA-
      cells were assessed for their ability to induce pokeweed mitogen-driven IgM and
      IgM-rheumatoid factor synthesis, and they were found to be potent helper/inducer
      cells. An increased population of CD7-, CD4+ cells in peripheral blood was found
      to predict a low response to recall antigens. CONCLUSION: The low expression of
      CD7 in RA may explain some of the immune abnormalities which may contribute to
      the pathogenesis of this disease.

PMID- 1376122
TI  - Phenotypic and functional similarities between 5-azacytidine-treated T cells and
      a T cell subset in patients with active systemic lupus erythematosus.
AB  - OBJECTIVE: Antigen-specific CD4+ T cells treated with DNA methylation inhibitors
      become autoreactive, suggesting a novel mechanism for autoimmunity. To test
      whether this mechanism might be involved in systemic lupus erythematosus (SLE),
      phenotypic markers for the autoreactive cells were sought. METHODS: Cloned normal
      T cells were treated with the DNA methylation inhibitor 5-azacytidine (5-azaC)
      and studied for altered gene expression. T cells from patients with active SLE
      were then studied for a similar change in gene expression, and cells expressing
      the marker were tested for autoreactivity. RESULTS: 5-azaC-treated normal T cells
      had increased CD11a (leukocyte function-associated antigen 1 alpha) expression
      relative to other membrane molecules. A T cell subset with similar CD11a
      expression was found in patients with active SLE. This subset contained cells
      that spontaneously lysed autologous macrophages, with a specificity similar to
      that of 5-azaC-treated cells.

PMID- 1376123
TI  - Restricted epitope recognition by precipitin-negative anti-La/SS-B-positive sera.
AB  - OBJECTIVE: To determine whether anti-La/SS-B-positive sera that are precipitin
      negative show a distinct B cell epitope pattern. METHODS: Serum reactivity was
      tested with recombinant La/SS-B fusion proteins. RESULTS: Among the 18 precipitin
      negative anti-La/SS-B-positive sera, reactivity was confined to the full-length
      recombinant protein (La33.3) in 8 (44%); 5 of 18 (28%) reacted only with La33.3
      and with the first 107 N-terminal amino acids (LaA), and 4 (22%) reacted with
      La33.3, LaA, and the middle region of the La molecule (LaC; amino acids 111-242).
      One serum reacted with La33.3 and LaC. None of the 18 precipitin-negative sera
      was positive on a carboxy-terminal fragment (LaL2/3; amino acids 346-408). In
      contrast, all 26 precipitin-positive anti-La/SS-B-positive sera reacted with
      La33.3, LaA, and LaC, and 92% reacted with LaL2/3. Rheumatoid factor and serum
      IgG levels were significantly lower in the precipitin-negative group, providing
      further evidence of a distinct serologic subset. CONCLUSION: The restricted
      epitope recognition by these sera may explain the lack of precipitin formation
      and may represent an early autoantibody response to La/SS-B.

PMID- 1376124
TI  - Lymphokine-activated killer cell and natural killer cell activities in patients
      with systemic sclerosis.
AB  - OBJECTIVE: To determine the ability of T lymphocytes and natural killer (NK)
      cells from patients with systemic sclerosis (SSc) to respond to cytokines and to
      generate immune effector cells. METHODS: The numbers and percentages of
      peripheral blood T and NK cells were examined by 2-color flow cytometry, and NK
      and lymphokine-activated killer (LAK) cell function were measured in 4-hour 51Cr
      release assays, in 34 patients with SSc. The patients were categorized into 3
      subgroups: 10 had diffuse cutaneous disease of less than or equal to 3 years
      disease duration, 11 had diffuse cutaneous SSc of greater than 3 years duration,
      and 13 had limited cutaneous disease. RESULTS: Baseline and activated NK and T
      cell numbers and NK activity were normal in SSc patients. However, mean LAK
      activity was significantly depressed in all SSc subgroups. CONCLUSION: Decreased
      LAK cell function, despite normal numbers of circulating T and NK cells,
      indicates that SSc patients have poor ability to produce effector cells in
      response to interleukin-2.

PMID- 1376125
TI  - [Characterization of the anti-cytokeratin monoclonal antibody KL1 by
      bidimensional electrophoresis followed by immunodetection].

PMID- 1376127
TI  - Reduced-size liver transplantation for infants and children.
AB  - Pediatric liver transplantation, although successful, was limited by the lack of
      available size-matched organs. Up to 25% to 50% of children died on the waiting
      list. RLT was initiated and developed to help alleviate donor shortage. Over
      time, RLT has proven to be an acceptable option for children requiring hepatic
      transplantation. In experienced centers survival rates are comparable to OLT, and
      long-term organ function is equally good. Future application of this technique
      may also provide more innovative approaches to pediatric liver transplantation.

PMID- 1376126
TI  - Effect of saffron on cell colony formation and cellular nucleic acid and protein
      synthesis.
AB  - A concentrated extract of saffron was prepared from the flowers of Crocus
      sativis. The effect of this extract on the ability of HeLa cells to form
      colonies, and on cellular DNA, RNA and protein synthesis was examined. Incubation
      of cells with extract for 3 h resulted in significant inhibition of colony
      formation and cellular nucleic acid synthesis with 50% inhibition at
      concentrations of approximately 100-150 micrograms/ml. In contrast there was no
      inhibition of cellular protein synthesis at concentrations of extract as high as
      400 micrograms/ml.

PMID- 1376128
TI  - Rapid differentiation of Pseudomonas pseudomallei from Pseudomonas cepacia.
AB  - The Minitek disc system was utilized for the differentiation of Pseudomonas
      pseudomallei, the causative agent of melioidosis, from Ps. cepacia. The system
      was simple to use, inexpensive, and furnished rapid, clear-cut test results after
      4 h. This procedure is suitable for differentiating soil bacteria presumptively
      identified as Ps. pseudomallei, Ps. cepacia or flavobacteria, and for the rapid
      confirmation of the presumptive identification of either Ps. pseudomallei or Ps.
      cepacia obtained by commercial identification-kit systems in the clinical
      laboratory.

PMID- 1376129
TI  - Modification of cell proliferation with inhibitors.
AB  - Recent developments on mechanisms that control cell multiplication, using
      molecular biology, are renewing interest in inhibitors and activators. A great
      deal of information has been gained in the past through the use of chemicals that
      modify passage through the cell cycle. The kinds of inhibitors, their sites of
      action that disrupt functions essential for proliferation, their usefulness in
      synchronizing cultures and, importantly, their therapeutic value, have been the
      subject of many investigations.

PMID- 1376131
TI  - Immunochemical characterization of Citrobacter strain PCM 1487 O-specific
      polysaccharide- and core oligosaccharide-protein conjugates.
AB  - O-specific-polysaccharide and core oligosaccharide were isolated from Citrobacter
      strain PCM 1487 lipopolysaccharide and purified. The polysaccharide was
      selectively devoid of 4-deoxy-D-arabinohexose residues. Covalent conjugates of
      the modified O-specific polysaccharide and of the core oligosaccharide with
      tetanus toxoid were prepared. Immunochemical characterization of these conjugates
      proved that they are strong immunogens. Using monospecific rabbit antisera raised
      against the conjugates, the antigenic relationships between lipopolysaccharides
      of various strains of Citrobacter, Shigella sonnei, and Shigella flexneri were
      studied by quantitative microprecipitin and quantitative microprecipitin
      inhibition and immunoblotting tests.

PMID- 1376130
TI  - Selectins and other mammalian sialic acid-binding lectins.
AB  - Several recently discovered mammalian cell adhesion proteins recognize and bind
      to sialic acid-containing ligands. Reports concerning the molecular specificities
      of these interactions have been intriguing but somewhat confusing, partly because
      of pitfalls in methodology or interpretation. Nevertheless, these protein
      carbohydrate recognition phenomena are important in the normal biology of blood
      cells and in the pathophysiology of many diseases.

PMID- 1376132
TI  - [Measurement of the distance among CK-4, Hox 3.1 and Hox 3.3 genes on mouse
      chromosome 15 by pulse field gel electrophoresis].
AB  - Pulse field gel electrophoresis (PFGE) and Southern hybridization analysis were
      used to measure the maximum distance between the mouse type II cytokeratin-4 gene
      and the homeobox-containing gene Hox 3.3 to be 130kb, and that between Hox 3.3
      and Hox 3.1 genes to be 50kb. Ck-4, Hox 3.1 and Hox 3.3 genes are mapped on mouse
      chromosome 15, and the order of loci is CK-4-Hox 3.3-Hox 3.1. A restriction map
      of Mlul, Notl, SacIl, Sal1 and Sfil restriction enzymes on a DNA fragment of
      1,100 kb in length on which those three genes located was constructed.

PMID- 1376133
TI  - Effectiveness of two palliative support teams.
AB  - The palliative care of 227 consecutive patients by two support teams was measured
      according to 17 key indicators in the Support Team Assessment Schedule (STAS), an
      instrument previously developed and validated for use in these settings. Mean
      time in care was 71 days (range 1-547); 56 per cent of patients died at home, 26
      per cent in hospital, 18 per cent in a hospice. Totalled ratings (sum of 15
      items, excluding two items owing to missed ratings) improved in 83 per cent of
      cases, remained unchanged in 3 per cent and deteriorated in 13 per cent. The main
      problems which the STAS identified at referral were family anxiety, symptom
      control, patient anxiety and communication between patient and family. Fifteen of
      the 17 items showed significant improvements (Wilcoxon Z ranged from -3.18 to 
      8.20, p less than 0.00005) between referral ratings and ratings for the last week
      of the patient's life; family anxiety and spiritual needs did not. Patient
      anxiety and symptom control, although improved, also remained relatively severe
      at death. These results demonstrate the value of measuring key indicators and
      indicate areas where improvement in palliative care is needed.

PMID- 1376134
TI  - Monoclonal antibodies to the C4 region of human immunodeficiency virus type 1
      gp120: use in topological analysis of a CD4 binding site.
AB  - We have raised antisera and monoclonal antibodies (MAbs) to the C4 region of HIV
      1 gp120, using an antigen chimaera of poliovirus as immunogen. These MAbs and
      sera, together with MAbs to the same region raised by other methods, fall into
      three groups defined by their abilities to bind to recombinant gp120 and/or the
      immunogenic peptide. In some cases, the amino acids recognized by the MAbs have
      been identified by pep-scan and by solution phase peptide inhibition of binding
      to recombinant gp120. Our results indicate that the amino acids WQEVGKAMYA are
      exposed on the surface of recombinant gp120. Antibodies to these amino acids on
      recombinant gp120 compete for soluble CD4 binding in vitro, but only weakly
      neutralize HIV.

PMID- 1376137
TI  - Cholera situation in the Americas. Update.

PMID- 1376135
TI  - Synergistic neutralization of HIV-1 by human monoclonal antibodies against the V3
      loop and the CD4-binding site of gp120.
AB  - Two distinct regions or epitope clusters of human immunodeficiency virus type 1
      (HIV-1) gp120 have been shown to elicit neutralizing antibodies: the V3 loop and
      the CD4-binding site. We have isolated neutralizing human monoclonal antibodies
      (HuMAbs) against conserved epitopes in both of these regions. In this study, we
      demonstrate that an equimolar mixture of two of these HuMAbs, one directed
      against the V3 loop and the other against the CD4-binding site, neutralizes HIV-1
      at much lower concentrations than does either of the individual HuMAbs.
      Mathematical analysis of this effect suggests cooperative neutralization of HIV-1
      by the two HuMAbs and demonstrates a high level of synergy, with combination
      indices (CIs) of 0.07 and 0.16 for 90% neutralization of the MN and SF-2 strains,
      respectively. The dose reduction indices (DRIs) for each of the two HuMAbs at 99%
      neutralization range approximately from 10 to 150. A possible mechanism for this
      synergism is suggested by binding studies with recombinant gp160 of the MN
      strain; these show enhanced binding of the anti-CD4 binding site HuMAb in the
      presence of the anti-V3 loop HuMAb. These results demonstrate the advantage of
      including both V3 loop and CD4-binding site epitopes in a vaccine against HIV-1
      and indicate that combinations of HuMAbs against these two sites may be
      particularly effective in passive immunotherapy against the virus.

PMID- 1376136
TI  - HIV-1 env, nef, and gag-specific T-cell immunity in mice: conserved epitopes in
      nef p27 and gag p25 proteins.
AB  - Cellular immunogenicity of env gp160, nef p27, and gag p55 proteins of human
      immunodeficiency virus type 1 (HIV-1) was studied in mice immunized with vaccinia
      virus recombinants. Proliferative responses of spleen cells were comparable
      against env gp160, nef p27, and gag p25 recombinant proteins. No specific
      activity was observed against gag p18 protein. Env, nef, and gag-specific T-cell
      lines were generated by repeated stimulation of immune spleen cells with
      recombinant HIV-1 proteins. They were CD4 positive, proliferative, and also
      cytotoxic against HIV-transfected target cells. Specificity of the T-cell
      response against nef and gag protein was analyzed with synthetic peptides.
      Peptides nef 15, nef 16, and gag AM-30 were, respectively, reactive in nef- and
      gag-specific proliferative and cytolytic assays. The three peptides described
      have a relatively conserved amino acid sequence among HIV isolates and appear
      broadly immunoreactive among species.

PMID- 1376138
TI  - Dengue and dengue haemorrhagic fever in the Americas: an overview of the problem.

PMID- 1376139
TI  - Increased risk for lung cancer and for cancer of the gastrointestinal tract among
      Geneva professional drivers.
AB  - A historical prospective cohort study of 6630 drivers from the Canton of Geneva
      was carried out to evaluate mortality and incidence of cancer in this occupation.
      The study population was all men (of all vocations) who held in 1949 a special
      licence for driving lorries, taxis, buses, or coaches and all new licence holders
      in the period 1949-61. Men born before 1900 and those with only an ordinary
      driving licence were excluded. According to the occupation registered on their
      licence, the 6630 drivers were distributed into three groups: (1) professional
      drivers (n = 1726), (2) non-professional drivers "more exposed" to exhaust gas
      and fumes (this group included occupations such as vehicle mechanic, policeman,
      road sweeper; n = 712), and (3) non-professional drivers "less exposed," composed
      of all other occupations (n = 4192). The cohort was followed up from 1949 to
      December 1986 and the trace of 197 men (3%) was lost. Compared with the general
      population of the Canton of Geneva, professional drivers experienced significant
      excess risks, taking into account 15 years of latency, for all causes of death
      (standardised mortality ratio (SMR) 115, 90% confidence interval (90% CI) 107
      123) and for all malignant neoplasms (SMR 125, 90% CI 112-140; standardised
      incidence ratio (SIR) 128, 90% CI 115-142). Cause specific analysis showed
      significant excesses for lung cancer (SMR 150, 90% CI 123-181; SIR 161, 90% CI
      129-198), oesophageal cancer (SMR 183, 90% CI 108-291), stomach cancer (SMR 179,
      90% CI 117-263; SIR233, 90% CI 156-336), rectal cancer (SMR 258, 90% CIU 162-392;
      SIR 200, 90% CI 127-300), and cirrhosis of the liver (SMR 145, 90% CI 104-198).
      Risk of lung cancer increased significantly with time from first exposure. Among
      non-professional drivers no significant excess risk was found except for lung
      cancer mortality among the "less exposed" group (SMR 121, 90% CI 103-140), and
      for incidence of lung cancer among the "more exposed" group (SIR 161, 90% CI 111
      227). The possible casual relation between exposure to engine exhaust emissions
      and the increased risk for lung cancer and for cancer of the gastrointestinal
      tract found among professional drivers is discussed.

PMID- 1376140
TI  - Molecular cloning of a differentiation-related mRNA in the adipogenic cell line
      1246.
AB  - The 1246 cell line is a C3H mouse teratoma-derived adipogenic cell line that can
      proliferate and differentiate in defined medium. We have constructed a
      recombinant phage library containing complementary DNAs (cDNAs) prepared from
      mRNA of differentiated 1246 cells. This library was screened using a differential
      hybridization technique. We have isolated five different cDNA clones
      corresponding to mRNAs that are induced during adipogenesis of 1246 cells and one
      cDNA clone corresponding to mRNA that is decreased during adipogenesis. Among the
      mRNAs expressed during adipose differentiation, some are not expressed in
      undifferentiated cells, whereas some are expressed at very low levels under these
      conditions. Moreover, the level of induction during differentiation and the
      temporal expression of the mRNAs corresponding to these cDNAs varied. Our results
      indicate that one of the cDNA clones isolated, called 154, which selects a 2.2
      kilobase mRNA, was induced 100-fold at a very early time during the onset of the
      differentiation program in 1246 cells and also in adipocyte precursors in primary
      culture. Direct sequencing of 154 cDNA insert revealed no homology with sequences
      in GenBank and PIR protein databases. The expression of 154 mRNA was stimulated
      by accelerators of differentiation such as dexamethasone and
      isobutylmethylxanthine and inhibited by tumor necrosis factor alpha, transforming
      growth factor beta, and epidermal growth factor, which are known inhibitors of
      1246 cell differentiation. In addition, 154 mRNA level in adipocytes was down
      regulated by tumor necrosis factor alpha, but not by transforming growth factor
      beta or epidermal growth factor. These results suggest that the increase in 154
      mRNA expression is related to the onset of adipose differentiation. Further
      analysis of this clone should allow characterization of a novel protein induced
      early during the process of differentiation.

PMID- 1376141
TI  - The int-2 gene product acts as a growth factor and substitutes for basic
      fibroblast growth factor in promoting the differentiation of a normal mouse
      mammary epithelial cell line.
AB  - We have investigated the effect of basic fibroblast growth factor (bFGF) and the
      related int-2 gene on the growth, transformation, and differentiation of HC11
      mouse mammary epithelial cells. We show that in HC11 cells infected with int-2
      retroviral expression vectors, the int-2 protein can function as a bFGF-like
      growth factor in stimulating: (a) HC11 cell proliferation in monolayer, (b)
      anchorage-independent growth in soft agar, and (c) soft agar growth of the bFGF
      responsive SW13 tumor cell line. These effects are observed irrespective of
      whether the int-2 protein is expressed in its wild-type form or is linked to a
      signal peptide. A candidate bFGF receptor, which is the product of the flg gene
      and which may recognize the int-2 protein, is expressed at high levels in HC11
      cells. Following epidermal growth factor or bFGF priming and subsequent treatment
      with lactogenic hormones, all of the int-2 infected and the parental HC11 cells
      synthesize similar levels of beta-casein. However, the autocrine expression of
      int-2 in HC11 cells abrogates their requirement for either exogenous epidermal
      growth factor or bFGF priming. These data suggest that, in HC11 cells, the growth
      factor activity of the int-2 gene is indistinguishable from that of bFGF and does
      not interfere with the mammary cell differentiation program associated with
      lactogenesis.

PMID- 1376142
TI  - Changes of epidermal cell morphology and keratin expression induced by inhibitors
      of protein kinase C.
AB  - Several lines of evidence show protein kinase C as being involved in various
      regulatory processes in keratinocyte biology, e.g. proliferation and
      differentiation. In the present study, we investigated the effects of three
      different inhibitors of protein kinase C, staurosporine, CP 46'665-1, and
      tiflucarbine, on cell morphology and keratin expression in a non-tumorigenic
      human keratinocyte cell line (HaCaT cells). Staurosporine, being the most potent
      inhibitor of protein kinase C activity in vitro, and CP 46'665-1 induced
      morphological transformation to a fibroblast-like cell shape. In contrast, no
      changes in cell morphology were observed after exposure to tiflucarbine. The
      investigation of keratin expression in HaCaT cells grown in the presence of the
      different compounds revealed the following changes: After 72 h of cultivation,
      keratins 8 and 18 were still expressed in treated cells, whereas expression of
      keratin 13 was decreased as compared to control cells. Immunoblotting to detect
      vimentin demonstrated its absence in treated and control cells. Since
      tiflucarbine is known as a dual protein kinase C/calmodulin inhibitor whereas
      staurosporine and CP 46'665-1 do not antagonize calmodulin function, it might be
      possible that not only protein kinase C but also calmodulin is involved in the
      process leading to the morphological changes.

PMID- 1376143
TI  - Perfluorocarbon liquid effects on corneal endothelial permeability.
AB  - We investigated the effects of perfluoro-n-octane liquid on the rabbit corneal
      endothelial permeability to inulin and dextran. Permeability measurements were
      made either after 10 minute in vitro exposure of the endothelium to 50
      microliters of the test liquid or after one week exposure in vivo following
      injection of 50 microliters of the test fluid into the anterior chamber.
      Retention of the perfluorocarbon on the in vitro cornea and in the anterior
      chamber during the appropriate exposure time was visually verified. The corneal
      endothelial permeability was unchanged after either short or sub-chronic
      treatment with perfluoro-n-octane indicating an absence of toxicity for this
      substance should it reach the cornea either intraoperatively or postoperatively.

PMID- 1376144
TI  - An unusual coloured compound in digests of senile nuclear cataract lens proteins.
AB  - An unusual pink compound has been isolated from the proteolytic digests of senile
      nuclear cataract proteins by adsorption onto Sephadex G-10. The tiny amounts
      obtained precluded definitive structural elucidation, however TLC comparisons
      show that it resembles triphenodioxazine-1,8-dicarboxylic acid, a pink
      heterocyclic chemical formed by oxidative condensation of 3-hydroxyanthranilic
      acid.

PMID- 1376145
TI  - Helical epitope of the group B meningococcal alpha(2-8)-linked sialic acid
      polysaccharide.
AB  - The immunological properties of the group B meningococcal alpha(2-8)-linked
      sialic acid polysaccharide have been rationalized in terms of a model where the
      random coil nature of the polymer can be described by the presence of local
      helices. The conformational versatility of the alpha NeuAc(2-8)alpha NeuAc
      linkage has been explored by NMR studies at 600 MHz in conjunction with potential
      energy calculations for colominic acid, an alpha(2-8)NeuAc polymer, and the
      trisaccharide alpha NeuAc(2-8)alpha NeuAc(2-8)beta NeuAc. Potential energy
      calculations were used to estimate the energetically favorable conformers and to
      describe the wide range of helices which the polymer can adopt. No unique
      conformer was found to satisfy all NMR constraints, and only ensemble averaged
      nuclear Overhauser enhancements could correctly simulate the experimental data.
      Conformational differences between the polymer and the trisaccharide could be
      best explained in terms of slight changes in the relative distribution of
      conformers in solution. Similar helical parameters for the alpha(2-8)NeuAc
      polymer and poly(A) were proposed as the basis for their cross-reactivity to a
      monoclonal antibody IgMNOV. The unusual length dependency for binding of
      oligosaccharide to group B specific antibodies was postulated to arise from the
      recognition of a high-order local helix with an extended conformation which was
      not highly populated in solution.

PMID- 1376146
TI  - Activation of the collagen-binding of endogenous serum vitronectin by heating,
      urea and glycosaminoglycans.
AB  - The present study describes that the collagen-binding activity of vitronectin in
      human serum increases by treatment with heparin, heating and urea. Vitronectin
      purified from human serum was bound to native collagen, whereas endogenous
      vitronectin in the serum was not. We have examined the conditions to change the
      collagen-binding activity of endogenous vitronectin. Endogenous vitronectin in
      human serum became considerably bound to collagen when the serum was boiled in 4
      8 M urea for 5 min and mixed with heparin (0.5-5 micrograms/ml). Each treatment
      of heating, urea or heparin alone, and any combination of the two factors,
      inefficiently activated the binding. Dextran sulfate could substitute for
      heparin, but dermatan sulfate, keratan sulfate, chondroitin sulfate A and C,
      heparan sulfate and hyaluronan could not. Possible explanations for the
      activation of endogenous vitronectin are discussed.

PMID- 1376147
TI  - Molecular cloning and characterization of mouse mast cell chymases.
AB  - Mouse mast cell chymases are granule-associated serine proteinases with
      chymotrypsin-like substrate specificities. cDNAs for two new chymases were
      isolated from a cDNA library constructed using mRNA from ABFTL-6 mouse mast cells
      by screening with a rat mast cell proteinase cDNA. The deduced amino acid
      sequence of mouse chymase 1 consists of a 226 amino acid catalytic portion and a
      21 amino acid preprosequence. Chymase 1 is unusual in that an Asn occurs in the
      substrate binding pocket, a feature that has not been observed in any other
      serine proteinase. Also, chymase 1 is expected to have a large positive charge
      (+13) at physiological pH. A partial cDNA for chymase 2 encodes 177 residues of
      the carboxy terminal portion of a second proteinase distinct from chymase 1.
      Chymase 2 cDNA contains a highly conserved intron/exon junction, a high positive
      charge (+17) and a novel, second potential N-glycosylation site. Transcripts for
      both chymases are found in ABFTL-6 mast cells, but only chymase 2 mRNA is in
      mouse connective tissue mast cells. These data suggest that these chymases have
      distinct enzymatic properties and tissue-specific patterns of gene expression.

PMID- 1376148
TI  - Sequential and combined G-banding for identifying breakpoints in sister chromatid
      exchanges.
AB  - A simple new method is described for obtaining sequential and a combination of
      differential sister chromatid staining and G-banding in the same metaphase. Using
      this method the sister chromatid exchanges and chromosome lesion breakpoints can
      be precisely localized in particular bands of individual chromosomes.

PMID- 1376149
TI  - Quality assurance and standardization in immunohistochemistry. A proposal for the
      annual meeting of the Biological Stain Commission, June, 1991.
AB  - Quality assurance, quality control, proficiency testing, reagent documentation
      and validation are standard parts of everyday practice in clinical laboratories
      throughout the United States. Immunohistochemical stains employ reagents and
      principles in common with immunoenzyme methods utilized in the clinical
      laboratory. However, immunohistochemistry has not routinely been subjected to
      similar standardization and quality assurance procedures that manufacturers and
      pathologists alike have applied to essentially the same techniques in the
      clinical laboratory environment. The current proposal was invited by the
      Biological Stain Commission with the charge of incorporating the findings of
      previous workshops on quality control in immunohistochemistry into a practical
      design for implementation. The status of quality assurance, quality control and
      standardization in immunohistochemistry is reviewed and a phased strategy for
      implementation is proposed.

PMID- 1376150
TI  - A two step stain for normal and leukemic monocytes using two different dyes
      applied in sequence.
AB  - A staining procedure for monocytes in specimens of blood and bone marrow was
      developed. The technique was a two step procedure in which unfixed cells were
      exposed first to a methanolic solution of C.I. basic blue 54. Next, an aqueous
      alkaline buffered solution of C.I. basic blue 141 was added to the first staining
      solution. After staining for 10 min in the solution with two stains, slides or
      coverslips were washed for 5 sec in pH 5.6 phosphate buffer and drained dry. The
      cytoplasm of monocytes stained intensely deep purple and frequently nuclei were
      stained red. Similar staining was not found in other types of normal or abnormal
      blood and bone marrow cells.

PMID- 1376151
TI  - Simultaneous measurement of DAPI-sulforhodamine 101 stained nuclear DNA and
      protein in higher plants by flow cytometry.
AB  - A 2-step staining procedure is presented for simultaneous measurement of nuclear
      DNA and protein content in higher plants by flow cytometry. To release nuclei,
      plant tissues were chopped and stirred in the presence of the DNA specific
      fluorochrome 4',6-diamidino-2-phenylindole (DAPI) and the nonionic detergent
      Triton X-100. Plant protoplasts were stirred in the DAPI dye solution with the
      detergent. After a short incubation period a second dye solution containing DAPI
      and the protein fluorochrome sulforhodamine 101 (SR 101) without detergent was
      added. Following another incubation, and after filtration through nylon gauze,
      the highly fluorescent nuclei were analyzed with an impulse cytophotometer.
      Accurate bivariate DNA-protein histograms were obtained with CV-values of about
      2% or less for the 2C-peak of the univariate DNA parameter. The method presented
      here can be used for basic and applied cytogenetic studies of higher plants, for
      characterization of subcompartments of the cell cycle phases, or for examination
      of heterogeneity in plant tissues.

PMID- 1376152
TI  - Unknown G0/G1 cell subpopulation revealed by hydrochloric acid/acridine orange
      staining.
AB  - An unknown cell subpopulation was observed in mouse and rat thymus, spleen and
      bone marrow cells, as well as in human peripheral blood mononuclear cells
      (resting and stimulated by PHA) using equilibrium HCl/acridine orange staining.
      This subpopulation includes cells with decreased green and unchanged red
      fluorescence. The staining does not affect cells in S- and G2/M-phases. The
      mechanism and biological meaning of the effect await further investigation.

PMID- 1376153
TI  - A modified Hortega-Globus stain is superior to Bielschowsky and Bodian stains for
      demonstrating neuritic plaques.
AB  - The quantitative assessment of the age-dependent number of neuritic plaques is
      essential for the diagnosis of Alzheimer type dementia. This study reports the
      superiority of a modified Hortega-Globus stain compared to Bielschowsky and
      Bodian stains applied to samples obtained from ten brains of patients with a
      clinical history of progressive dementia. In two of ten cases only the modified
      Hortega-Globus stain allowed confirmation of the diagnosis of senile dementia of
      the Alzheimer type (SDAT). The counts of neuritic plaques in sections stained by
      other methods were not sufficient to establish the histological diagnosis of
      SDAT. These results indicate that the choice of the most sensitive staining
      method is critical for the correct histopathologic diagnosis of the Alzheimer
      type dementia.

PMID- 1376154
TI  - Block-surface staining for differentiation of starch and cell walls in wheat
      endosperm.
AB  - A staining technique for differentiating starch granules and cell walls was
      developed for computer-assisted studies of starch granule distribution in cells
      of wheat (Triticum aestivum L.) caryopses. Blocks of embedded caryopses were
      sectioned, exposing the endosperm tissue, and stained with iodine potassium
      iodide (IKI) and Calcofluor White. Excessive tissue hydration during staining was
      avoided by using stains prepared in 80% ethanol and using short staining times.
      The IKI quenched background fluorescence which facilitated the use of higher
      concentrations of Calcofluor White. Cell wall definition was improved with the
      IKI-Calcofluor staining combination compared to Calcofluor alone. The high
      contrast between darkly stained starch granules and fluorescent cell walls
      permitted computer assisted analysis of data from selected hard and soft wheat
      varieties. The ratio of starch granule area to cell area was similar for both
      wheat classes. The starch granule sizes ranged from 2.1 microns 3 to 22,000
      microns 3 with approximately 90% of the granules measuring less than 752 microns
      3 (ca. 11 microns in diameter). Hard wheat samples had a greater number of small
      starch granules and a lower mean starch granule area compared to the soft wheat
      varieties tested. The starch size distribution curve was bimodal for both the
      hard and soft wheat varieties. Three-dimensional starch size distribution was
      measured for four cells near the central cheek region of a single caryopsis. The
      percentage of small granules was higher at the ends than at the mid-section of
      the cells.

PMID- 1376155
TI  - Pre-analytical and biological variability of prostatic acid phosphatase and
      prostate-specific antigen in serum from patients with prostatic pathology.
AB  - We determined the pre-analytical and biological variation of prostatic acid
      phosphatase and prostate-specific antigen in the same patient samples. Prostatic
      acid phosphatase and prostate-specific antigen were both stable when stored for
      at least 3 weeks with acidification (acetate buffer) or without acidification,
      except for prostate-specific antigen in samples stored unacidified at 4 degrees
      C. A significant elevation of prostate-specific antigen was noted in four
      patients with benign prostatic hyperplasia between 1/2 and 6 hours after
      prostatic massage. No significant effect was shown of changes in the glomerular
      filtration rate on prostate-specific antigen concentration, in spite of its low
      molecular mass. The estimate of within-subject biological variation showed a
      coefficient of variation of 33.8% for prostatic acid phosphatase and 14% for
      prostate-specific antigen. Desirable analytical imprecisions based on these
      findings were about 17% for prostatic acid phosphatase and 7% for prostate
      specific antigen, these goals being achieved in practice for marker values higher
      than or equal to the upper reference limit.

PMID- 1376156
TI  - Infections and pseudoinfections due to povidone-iodine solution contaminated with
      Pseudomonas cepacia.
AB  - In 1989 we investigated the first instance of Pseudomonas cepacia infections due
      to intrinsic contamination of a povidone-iodine product. Six patients in a Texas
      pediatric facility had P. cepacia infection or pseudoinfection (three,
      peritonitis; one, pseudoperitonitis; and two, pseudobacteremia). Epidemiological
      studies showed one risk factor for infection of peritoneal fluid with P. cepacia:
      performance of peritoneal dialysis in the dialysis unit with use of one lot of
      povidone-iodine later found to be intrinsically contaminated (4/5 vs. 0/16, P =
      .001). Blood cultures yielded P. cepacia after nurses wiped the tops of blood
      culture bottles with the povidone-iodine solution before inoculation. P. cepacia
      was cultured from three povidone-iodine containers used at the hospital and from
      four containers of the same lot obtained from other health-care facilities in
      Texas and California. Isolates from patients and the povidone-iodine had similar
      antibiograms, identical plasmid profiles, and identical DNA banding patterns on
      the basis of results of ribonucleotide typing. This investigation demonstrates
      that intrinsic contamination of povidone-iodine solution with P. cepacia can
      result in infections in addition to colonization and/or pseudoinfection.

PMID- 1376157
TI  - Influence of ion occupancy and membrane deformation on gramicidin A channel
      stability in lipid membranes.
AB  - The average lifetime of gramicidin A channels in monoolein/decane bilayer
      membranes was measured. The results support the hypothesis of channel
      stabilization by ion occupancy. The effects of electric field and salt
      concentration are consistent with the expected effects on both occupancy and
      membrane compression. The lifetime in asymmetric solutions with divalent cation
      blockers on one side of the membrane shows a voltage dependence such that the
      lifetime decreases for positive voltages applied from the blocking side and
      increases for negative voltages. This result strongly supports the occupancy
      hypothesis. The lifetime increases with permeant ion concentration, and at the
      one molar level it also increases with voltage. The voltage dependence of
      lifetime for a low concentration of permeant ion depends on the total salt level.
      The results for these conditions are consistent with the assumption that membrane
      compression also influences the lifetime, even for the "soft" solvent-containing
      membrane considered here. It is proposed that the channel nearest neighbor lipids
      need not be fixed in a plane at the channel end. Using a liquid crystal model it
      may then be shown that surface tension is the major component of the membrane
      deformation free energy, which may explain the significant effects of the
      membrane compression on the lifetime.

PMID- 1376158
TI  - Dynamic ion-ion and water-ion interactions in ion channels.
AB  - The dynamic interactions among ions and water molecules in ion channels are
      treated based on an assumption that ions at binding sites can be knocked off by
      both transient entering ions and local water molecules. The theory, when applied
      to a single-site model K+ channel, provides solutions for super- and
      subsaturations, flux-ratio exponent (n') greater than 1, osmotic streaming
      current, activity-dependent reversal potentials, and anomalous mole-fraction
      behavior. The analysis predicts that: (a) the saturation may but, in general,
      does not follow the Michaelis-Menten relation; (b) streaming current results from
      imbalanced water-ion knock-off interactions; (c) n' greater than 1 even for
      single-site channels, but it is unlikely to exceed 1.4 unless the pore is
      occupied by one or more ion(s); (d) in the calculation involving two permeant ion
      species with similar radii, the heavier ions show higher affinity; the ion-ion
      knock-off dissociation from the site is more effective when two interacting ions
      are identical. Therefore, the "multi-ion behaviors" found in most ion channels
      are the consequences of dynamic ion-ion and water-ion interactions. The presence
      of these interactions does not require two or more binding sites in channels.

PMID- 1376159
TI  - Constant fields and constant gradients in open ionic channels.
AB  - Ions enter cells through pores in proteins that are holes in dielectrics. The
      energy of interaction between ion and charge induced on the dielectric is many
      kT, and so the dielectric properties of channel and pore are important. We
      describe ionic movement by (three-dimensional) Nemst-Planck equations (including
      flux and net charge). Potential is described by Poisson's equation in the pore
      and Laplace's equation in the channel wall, allowing induced but not permanent
      charge. Asymptotic expansions are constructed exploiting the long narrow shape of
      the pore and the relatively high dielectric constant of the pore's contents. The
      resulting one-dimensional equations can be integrated numerically; they can be
      analyzed when channels are short or long (compared with the Debye length).
      Traditional constant field equations are derived if the induced charge is small,
      e.g., if the channel is short or if the total concentration gradient is zero. A
      constant gradient of concentration is derived if the channel is long. Plots
      directly comparable to experiments are given of current vs voltage, reversal
      potential vs. concentration, and slope conductance vs. concentration. This
      dielectric theory can easily be tested: its parameters can be determined by
      traditional constant field measurements. The dielectric theory then predicts
      current-voltage relations quite different from constant field, usually more
      linear, when gradients of total concentration are imposed. Numerical analysis
      shows that the interaction of ion and channel can be described by a mean
      potential if, but only if, the induced charge is negligible, that is to say, the
      electric field is spatially constant.

PMID- 1376160
TI  - The cystic fibrosis transmembrane conductance regulator chloride channel. Iodide
      block and permeation.

PMID- 1376161
TI  - Sizing of an ion pore by access resistance measurements.

PMID- 1376162
TI  - The role of Pro/Hyp-kinks in determining the transmembrane helix length and
      gating mechanism of a [Leu]zervamicin channel.

PMID- 1376163
TI  - Large scale rearrangement of protein domains is associated with voltage gating of
      the VDAC channel.
AB  - The VDAC channel of the mitochondrial outer membrane is voltage-gated like the
      larger, more complex voltage-gated channels of the plasma membrane. However, VDAC
      is a low molecular weight (30 kDa), abundant protein, which is readily purified
      and reconstituted, making it an ideal system for analyzing the molecular basis
      for ion selectivity and voltage-gating. We have probed the VDAC channel by
      subjecting the cloned yeast (S. cerevisiae) VDAC gene to site-directed
      mutagenesis and introducing the resulting mutant channels into planar bilayers to
      detect the effects of specific sequence changes on channel properties. This
      approach has allowed us to formulate and test a model of the open state structure
      of the VDAC channel. Now we have applied the same approach to analyzing the
      structure of the channel's low-conducting "closed state" (essentially closed to
      important metabolites). We have identified protein domains forming the wall of
      the closed conformation and domains that seem to be removed from the wall of the
      pore during channel closure. The latter can explain the reduction in pore
      diameter and volume and the dramatically altered channel selectivity resulting
      from the channel closure. This process would make a natural coupling between
      motion of the sensor and channel gating.

PMID- 1376164
TI  - Formation of non-beta 6.3-helical gramicidin channels between sequence
      substituted gramicidin analogues.
AB  - Using the linear gramicidins as an example, we have previously shown how the
      statistical properties of heterodimeric (hybrid) channels (formed between the
      parent [Val1]gramicidin A (gA) and a sequence-altered analogue) can be used to
      assess whether the analogue forms channels that are structurally equivalent to
      the parent channels (Durkin, J. T., R. E. Koeppe II, and O. S. Andersen. 1990. J.
      Mol. Biol. 211:221-234). Generally, the gramicidins are tolerant of amino acid
      sequence alterations. We report here an exception. The optically reversed
      analogue, gramicidin M- (gM-) (Heitz, F., G. Spach, and Y. Trudelle. 1982.
      Biophys. J. 40:87-89), forms channels that are the mirror-image of [Val1]gA
      channels; gM- should thus form no hybrid channels with analogues having the same
      helix sense as [Val1]gA. Surprisingly, however, gM- forms hybrid channels with
      the shortened analogues des-Val1-[Ala2]gA and des-Val1-gC, but these channels
      differ fundamentally from the parent channels: (a) the appearance rate of these
      heterodimers is only approximately 1/10 of that predicted from the random
      assortment of monomers into conducting dimers, indicating the existence of an
      energy barrier to their formation (e.g., monomer refolding into a new channel
      forming conformation); and (b), once formed, the hybrid channels are stabilized
      approximately 1,000-fold relative to the parent channels. The increased stability
      suggests a structure that is joined by many hydrogen bonds, such as one of the
      double-stranded helical dimers shown to be adopted by gramicidins in organic
      solvents (Veatch, W. R., E. T. Fossel, and E. R. Blout. 1974. Biochemistry.
      13:5249-5256).

PMID- 1376165
TI  - Mutational analysis of gap junction formation.
AB  - The paired oocyte cell-cell channel assay was used to investigate the mechanisms
      involved in the process of formation of gap junction channels. Single oocytes,
      injected with connexin-specific mRNAs, accumulate a pool of precursors from which
      cell-cell channels can form rapidly upon pairing. Several lines of evidence,
      including immunohistochemistry and surface labeling, indicate that part of this
      precursor pool is located in the cell membrane, probably in the form of closed
      hemichannels. The homophilic binding of hemichannels to each other can be
      mimicked by synthetic peptides representing the extracellular loop sequences of
      connexin32. The peptides specifically suppress channel formation. A crucial role
      is established for the six cysteines in the extracellular domains that are
      conserved in all vertebrate gap junction proteins. Change of any of these
      cysteines into serines results in absolute loss of function of the mutant
      connexin. The effects of thiol-specific reagents on channel formation suggest
      that docking and/or opening of channels involves disulfide exchange. Several of
      the variable amino acids in the extracellular loop sequences were found to
      determine specificity of connexin-connexin interactions.

PMID- 1376166
TI  - Molecular analysis of voltage dependence of heterotypic gap junctions formed by
      connexins 26 and 32.
AB  - Heterotypic gap junctions formed by pairing Xenopus oocytes expressing
      hemichannels formed of Cx32 with those expressing hemichannels formed of Cx26
      displayed novel transjunctional voltage (Vj) dependence not predicted by the
      behavior of these connexins in homotypic configurations. Rectification of initial
      and steady-state currents was observed. Relative positivity and negativity on the
      Cx26 side of the junction resulted in increased and decreased initial conductance
      (gj0), respectively. Only relative positivity on the Cx26 decreased steady-state
      conductance (gj infinity). This behavior suggested that interactions between
      hemichannels influences gap junction gating. The role of the first extracellular
      loop (E1) in these interactions was examined by pairing Cx32 and Cx26 with a
      chimeric connexin in which Cx32 E1 was replaced with Cx26 E1 (Cx32*26E1). Both
      junctions rectified with gj0/Vj relations that were less steep than that observed
      for Cx32/Cx26. Decreases in gj infinity occurred for either polarity Vj in the
      Cx32/Cx32*26E1 junction. Mutation of two amino acids in Cx26 E1 increased the
      steepness of both the gj0/Vj and gj infinity/Vj relations. These data demonstrate
      that fast rectification can arise from mismatched E1 domains and that E1 may
      contribute to the voltage sensing mechanisms underlying both fast and slow Vj
      dependent processes.

PMID- 1376167
TI  - Threonine in the selectivity filter of the acetylcholine receptor channel.
AB  - The acetylcholine receptor (AChR) is a cation selective channel whose biophysical
      properties as well as its molecular composition are fairly well characterized.
      Previous studies on the rat muscle alpha-subunit indicate that a threonine
      residue located near the cytoplasmic side of the M2 segment is a determinant of
      ion flow. We have studied the role of this threonine in ionic selectivity by
      measuring conductance sequences for monovalent alkali cations and bionic reversal
      potentials of the wild type (alpha beta gamma delta channel) and two mutant
      channels in which this threonine was replaced by either valine (alpha T264V) or
      glycine (alpha T264G). For the wild type channel we found the selectivity
      sequence Rb greater than Cs greater than K greater than Na. The alpha T264V
      mutant channel had the sequence Rb greater than K greater than Cs greater than
      Na. The alpha T264G mutant channel on the other hand had the same selectivity
      sequence as the wild type, but larger permeability ratios Px/PNa for the larger
      cations. Conductance concentration curves indicate that the effect of both
      mutations is to change both the maximum conductance as well as the apparent
      binding constant of the ions to the channel. A difference in Mg2+ sensitivity
      between wild-type and mutant channels, which is a consequence of the differences
      in ion binding, was also found. The present results suggest that alpha T264 form
      part of the selectivity filter of the AChR channel were large ions are selected
      according to their dehydrated size.

PMID- 1376168
TI  - Amino acid substitutions and ion channel function. Model-dependent conclusions.

PMID- 1376169
TI  - A dipolar amino acid substitution induces voltage-dependent transitions between
      two stable conductance states in gramicidin channels.

PMID- 1376170
TI  - Gating currents from a delayed rectifier K+ channel with altered pore structure
      and function.

PMID- 1376171
TI  - Locating a residue in the diphtheria toxin channel.
AB  - We are studying structure-function relationships in the Diphtheria Toxin (DT)
      channel using a combination of site-directed mutagenesis and electrophysiology in
      artificial lipid bilayers. We made site-directed mutations of charged residues in
      the toxin's channel-forming B fragment, and after expressing the mutant proteins
      in Escherichia coli, we analyzed the single channels they formed in lipid
      bilayers. Changing aspartate 352, which is located in a short hydrophilic loop
      separating two hydrophobic stretches, to asparagine or lysine dramatically
      reduces the single-channel conductance of the pore at pH 5.3 cis, 7.2 trans
      (5.3/7.2). Lowering the pH on both sides of the membrane essentially eliminates
      the difference between wild-type and D352N; this finding is consistent with the
      idea that an aspartate with a (protonated) neutral side-chain and the always
      neutral asparagine have similar electrostatic influences on permeant ions. Using
      a high concentration of permeant buffer to clamp the pH of the cis compartment
      and the pore, and varying the pH on the trans side, we have located D352 at or
      near the trans compartment. We further find that D352N channels, in contrast to
      wild-type, display conductances independent of trans pH. This observation allows
      us to determine the titration curve of aspartate 352 in the wild-type toxin,
      establishing its pKa at approximately 5.5.

PMID- 1376173
TI  - A point mutation in a Shaker K+ channel changes its charybdotoxin binding site
      from low to high affinity.

PMID- 1376172
TI  - Gating of gap junction channels as revealed in cells stably transfected with wild
      type and mutant connexin cDNAs.

PMID- 1376174
TI  - Phosphorylation shifts unitary conductance and modifies voltage dependent
      kinetics of human connexin43 gap junction channels.

PMID- 1376175
TI  - The extracellular domain of substance P (NK1) receptor comprises part of the
      ligand binding site.

PMID- 1376176
TI  - Mapping hydrophobic residues of the interaction surface of charybdotoxin.

PMID- 1376178
TI  - Regulation of cultured human mesangial cell growth by ionized macromolecules.
AB  - We evaluated the importance of the net charge of polyionic macromolecules in the
      regulation of cultured human mesangial cell growth. Structurally unrelated
      polyanionic compounds, i.e., heparin, suramin, poly-L-aspartic acid, and poly-L
      glutamic acid, strongly inhibited 10% fetal bovine serum-stimulated cell
      proliferation. On the other hand, two polycations, protamin sulfate and poly-L
      lysine, were equally effective in inhibiting cell growth. The antiproliferative
      activity of each compound was neutralized by molecules with opposite net charge.
      These data indicate that both anionic and cationic macromolecules exert an
      antimitogenic effect on cultured human mesangial cells. This inhibitory effect is
      dependent upon charge density rather than on the net electric charge of each
      compound.

PMID- 1376177
TI  - The effect of polyimmune gammaglobulin for prophylaxis against reactivation
      cytomegalovirus infection in kidney and kidney/pancreas transplant recipients.
AB  - Cytomegalovirus (CMV) remains the most important infection in the renal
      transplant recipient. Few data are available that provide guidance for approaches
      that seek to reduce the reactivation of latent disease after transplantation. To
      test the efficacy of polyimmune gammaglobulin in kidney and kidney/pancreas
      transplantation, consenting recipients with serologic evidence of previous CMV
      disease were randomized to receive i.v. polyimmune gammaglobulin (500 mg/kg)
      within 3 days of transplant with 250 mg/kg at weeks 1, 2, 4, and 6 or no
      prophylaxis. Both groups received identical induction and rejection
      immunosuppressive therapy. Polyimmune gammaglobulin prophylaxis reduced CMV
      reactivation infections. The incidence of reactivation infections was half in
      patients receiving Nashville/rabbit antithymocyte serum (N/R-ATS) compared with
      those receiving monoclonal anti-CD-3 therapy. Patients receiving polyimmune
      gammaglobulin along with N/R-ATS had an incidence of infection of only 10%.
      Reactivation infections were twice as common in patients who had primary
      nonfunction and nearly three times as common in patients with acute rejection.
      Both risk factors were associated with longer anti-T-cell therapy. Polyimmune
      gammaglobulin prophylaxis should be considered in transplant patients with
      previous CMV exposure who will be receiving prolonged anti-T-cell therapy because
      of acute rejection or primary nonfunction.

PMID- 1376179
TI  - Ovarian and hepatic metastases of gastric carcinoma associated with high serum
      levels of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and
      carcinoembryonic antigen (CEA): a case report.
AB  - A 45-year-old woman who underwent gastrectomy for gastric carcinoma which had
      metastasized to the liver and ovaries, showed high serum levels of hCG, AFP and
      CEA. To locate the source, an immunohistochemical technique was utilized. HCG
      producing cells were detected in poorly differentiated adenocarcinoma of a
      primary tumor and an ovarian metastatic site, and AFP-producing cells in poorly
      differentiated adenocarcinoma forming a medullary pattern of primary site and
      metastatic foci. CEA-producing cells were found diffused in primary tumor and
      metastatic foci. From the viewpoint of oncodevelopmental gene expression (Cancer
      Res 36:3423, 1976), it is interesting that the serum levels of these three tumor
      markers (hCG, AFP, CEA) were elevated simultaneously.

PMID- 1376180
TI  - Granulocyte colony-stimulating factor-producing large cell undifferentiated
      carcinoma of the lung.
AB  - We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung
      cancer. A 38-year-old Japanese woman had a large cell undifferentiated carcinoma
      of the left lung with severe granulocytosis without any evidence of infection. A
      specimen was taken from a metastatic cervical lymph node and a tumor cell line
      was established. The culture supernatant of the line as well as patient's serum
      exhibited a high level of G-CSF by sandwich enzyme immunoassay.
      Immunohistochemical analysis demonstrated that tumor cells from transplanted nude
      mice were stained granularly in the cytoplasma by anti-human G-CSF monoclonal
      antibody, 4A6.

PMID- 1376181
TI  - Carnitine deficiency: a possible cause of gastrointestinal dysmotility.
AB  - An infant with delayed development and peripheral myopathy, nourished on a soy
      based liquid diet deficient in carnitine, had gastrointestinal dysmotility
      manifested by postprandial vomiting, oral drooling, delayed gastric emptying and
      infrequent bowel movements. Oesophageal manometry showed a reduced lower
      oesophageal sphincter pressure for age with abnormal distal motility. Serum
      carnitine concentration was 9.9 mumol l-1. After dietary supplementation of
      carnitine the gastrointestinal symptoms resolved, oesophageal manometry returned
      to normal, and serum carnitine increased to 37.2 mumol l-1. Dietary carnitine
      deficiency in infancy may be a cause of smooth muscle dysmotility of the
      gastrointestinal tract.

PMID- 1376182
TI  - Mild course of cystic fibrosis associated with heterozygosity for infrequent
      mutations in the first nucleotide-binding fold of CFTR.
AB  - The mild clinical course of a patient with cystic fibrosis is presented who
      inherited the two mutations Gly551----Asp and Arg553----Stop in the cystic
      fibrosis transmembrane conductance regulator gene. The missense mutation Arg553--
      -Stop discovered in American Blacks is also present on cystic fibrosis
      chromosomes of Caucasian ancestry.

PMID- 1376183
TI  - Cardiac rhythm in healthy elderly subjects.
AB  - To study the normal cardiac rhythm in elderly subjects we performed 24-h Holter
      monitoring on 94 subjects aged over 70 years. We had previously discarded those
      with cardiac disease by using history, physical examination, electrocardiography
      (ECG), chest X-radiography and Doppler echocardiography. The maximum, average and
      minimum heart rates were 113, 79 and 62, respectively, during the day, and 90, 64
      and 53 during the night. Supraventricular and ventricular arrhythmias were
      frequent (91% and 89.4%, respectively). Some 50% of the subjects had complex
      ventricular arrhythmias. Two subjects presented with sinus pauses of more than 2
      s, and 4 had Wenckebach second-degree atrioventricular (AV) block. During a
      follow-up averaging 20.8 months, there were no deaths or symptoms of an
      arrhythmic origin.

PMID- 1376184
TI  - [Prevalence of hepatitis C virus in poly-transfused patients with hematologic and
      oncologic diseases].
AB  - Patients with hematological and oncological diseases often require intensive,
      supportive hematotherapy due to the underlying disease or chemo-/radiotherapy. As
      a consequence, they had an increased transfusion-associated risk of hepatitis C
      virus infections (non-A, non-B-posttransfusion hepatitis) until 1989-1990, when
      specific and sensitive HCV antibody tests became available. This is confirmed by
      our study of 'first' and 'second' generation (1.0 and 2.0) anti-HCV EIAs against
      structural and non-structural (NS) antigen-determinants. Ten of 101 patients
      (10.9%) were anti-HCV positive in 2.0 tests. HCV antibodies were detected more
      often by 2.0 EIAs and the new HCV-immunoblot (4-RIBA), than by 1.0 EIAs. In this
      respect, the patients' serological HCV profile differs from that of healthy blood
      donors, which display a prevalence of NS-antibodies.

PMID- 1376185
TI  - Comparison of hematopoietic and immune recovery after autologous bone marrow or
      blood stem cell transplants.
AB  - We studied hematopoietic and immune recovery in 40 subjects receiving autologous
      bone marrow (ABMT) or blood stem cell transplants (ABSCT). Supportive care,
      transplant-related morbidity, duration of hospitalization and cost were also
      considered. ABSCT was associated with more rapid recovery of all hematopoietic
      lineages than was ABMT. However, kinetics of immune recovery were similar between
      the groups. In the ABSCT group, there was a correlation between numbers of blood
      progenitor cells infused and the rate of hematopoietic recovery. The accelerated
      hematopoietic recovery following ABSCT correlated with less morbidity, fewer
      transfusions, briefer hospitalization and lower cost than ABMT.

PMID- 1376186
TI  - Sideroblastic anemia following autotransplantation for Hodgkin's disease using
      rHu-G-CSF.

PMID- 1376187
TI  - [RP 67580, a potent and selective substance P non-peptide antagonist].
AB  - The pharmacological properties of 7,7-Diphenyl-2 [1-imino-2 (2-methoxy-phenyl)
      ethyl] perhydroisoindol-4-one (3 aR, 7 aR) or RP67580 are described. This
      compound, derived from a novel chemical family, is a potent and selective
      substance P (SP) antagonist, in vitro and in vivo. In vitro, it inhibited in a
      competitive manner (IC50 = 10 nM) 3H-SP binding in rat brain (NK1 receptors). It
      did not interact with the two other tachykinin receptor sites (NK2 and NK3) nor
      the other receptor sites tested. Moreover, RP67580 competitively antagonized the
      contractile activity of SP on guinea-pig ileum (pA2 = 7.16); in contrast, it was
      inactive in rabbit pulmonary artery and in rat portal vein tissues which contain
      NK2 and NK3 receptors, respectively. In vivo, in the rat, RP67580 inhibited the
      plasmatic extravasation induced by administration of SP (ED50 = 0.04 mg/kg i.v.)
      as well as that induced by antidromic stimulation of a peripheral sensory nerve
      (ED50 = 0.15 mg/kg i.v.). In mice and rats, RP67580, like morphine, potently
      blocked the nociceptive effects of phenylbenzoquinone and formalin; its
      antinociceptive effect does not involve opiate receptors since it was not
      reversed by naloxone. These results indicate that RP67580 is a particularly
      valuable tool for investigating the physiological and pathological role of SP.

PMID- 1376188
TI  - Acute exposure to human interferon-alpha affects ion currents in human natural
      killer cells.
AB  - Interferon-alpha (IFN-alpha) is a particularly potent stimulator of human natural
      killer (NK) cell activity. The initial trigger for IFN action is not known, but
      there is indirect evidence from a number of cell types that changes in ion
      channel activity are among the earliest responses. Previous evidence includes
      changes in Ca2+ fluxes and intracellular activity, membrane potential changes,
      and effects of ion-channel blockers. Killing by human NK cells is dependent on
      external Ca2+ and on K+ channel activity. In the present study we have confirmed
      this dependence and the augmentation by human IFN-alpha. Then we directly studied
      the effects of IFN-alpha on ion currents in human NK cells using the patch-clamp
      electrophysiological techniques. We find that IFN-alpha can increase the
      predominant K+ current near the resting potential but suppresses it at higher
      voltages. Within 1 min after acute IFN-alpha treatment a new current is induced.
      This small current appears to be through nonselective cation channels that allow
      monovalent and divalent cations, including Ca2+ to permeate. This current
      presents a possible early triggering mechanism whereby acute exposure to IFN
      alpha augments NK cytotoxicity.

PMID- 1376189
TI  - American Cancer Society/ American Urological Association International Workshop
      on Prostatic Cancer and Hyperplasia. Sea Island, Georgia, October 26-29, 1991.

PMID- 1376190
TI  - Predicted prostate specific antigen results using transrectal ultrasound gland
      volume. Differentiation of benign prostatic hyperplasia and prostate cancer.
AB  - METHODS: The diagnostic performance of transrectal ultrasound (TRUS) gland volume
      and prostate specific antigen (PSA) results were evaluated in 204 men
      consecutively scheduled to undergo transurethral prostatic resection (TUR).
      RESULTS: Nonpalpable prostate cancer was detected by TRUS alone in 18% (29 of
      161) and by TUR alone in 9% (14/161), for an overall cancer incidence of 27%. A
      predicted PSA value (TRUS gland volume x 0.20 ng/ml/g = polyclonal PSA) was used
      for comparison with serum PSA for each patient. TRUS positive predictive value
      improved from 52% to 86% when serum PSA exceeded the predicted value. The
      specificity and positive predictive value of PSA at 2.5 ng/ml were 23% and 37%,
      respectively, which increased to 88% and 72%, respectively, when serum PSA
      exceeded the predicted value. CONCLUSIONS: Predicted PSA values produce decision
      levels near the 95th percentile for each patient and assist individual biopsy
      decisions better than grouped gland volume ranges. Wider application of TRUS and
      PSA in any clinical setting or early detection program is now possible.

PMID- 1376191
TI  - Clinical diagnosis of prostate cancer.
AB  - BACKGROUND: The clinical diagnosis of localized prostate carcinoma in the
      asymptomatic male has been based on a careful digital rectal examination (DRE).
      METHODS: The DRE, prostate specific antigen (PSA), transrectal ultrasonography
      (TRUS), prostate needle biopsy (PNB), and other modalities are examined for their
      role in prostate cancer diagnosis. RESULTS: Up to 20% of localized prostatic
      cancer is still diagnosed "retrospectively" on transurethral resection (TURP) for
      clinically benign disease and prostatism. The role of fine-needle aspiration
      (FNA), flow cytometric study (FCM), and magnetic resonance imaging (MRI) in the
      diagnosis of prostate cancer is limited. CONCLUSIONS: Those men older than 50
      years of age who have lower tract symptoms, either obstructive or irritative, or
      who have abnormal serum levels of PSA, regardless of DRE findings, are advised to
      undergo TRUS with ultrasound-guided PNB.

PMID- 1376192
TI  - Tumor markers in prostate cancer.
AB  - Prostatic specific antigen (PSA) is a tissue specific marker that is now the most
      widely used biochemical test for the assessment and follow-up of prostate cancer.
      The levels of PSA rise with tumor stage, but there is considerable overlap of
      their distribution between stages. PSA measurement now forms a part of the workup
      of a suspected carcinoma of the prostate, with a level of more than 4 ng/ml being
      an indication for further investigation. The sensitivity of PSA makes it an
      essential test for the postoperative assessment of radical prostatectomy and
      curative radiation therapy. The rates of change of PSA levels in locally advanced
      and metastatic disease treated by hormone manipulation can provide prognostic
      information. Low levels of PSA (less than 10 ng/ml) 6 months after treatment are
      a sign that the response will be prolonged. However, the sensitivity of PSA often
      results in a rising level preceding clinical evidence of progression by several
      months and is not necessarily an indication to change treatment. Alkaline
      phosphatase and prostatic acid phosphatase provide a less sensitive test for the
      bone response to skeletal metastases and tumor activity in advanced disease,
      respectively.

PMID- 1376193
TI  - Prostate specific antigen predominantly forms a complex with alpha 1
      antichymotrypsin in blood. Implications for procedures to measure prostate
      specific antigen in serum.
AB  - BACKGROUND: Prostate specific antigen (PSA) is a zymogen of a 33-kilodalton (kD)
      serine proteinase with extensive similarity to glandular kallikreins. The
      mechanism responsible for converting the zymogen into active proteinase has not
      been defined, but active PSA may be irreversibly inactivated in vitro by two of
      the major proteinase inhibitors in blood: alpha 1-antichymotrypsin and alpha 2
      macroglobulin. METHODS: Procedures have been designed to characterize the
      different molecular forms of PSA in serum. One assay detects PSA epitopes
      available on both PSA binding to serine proteinase inhibitors and PSA not binding
      to a proteinase inhibitor. A second assay only detects PSA in complex with alpha
      1-antichymotrypsin. A third assay mainly detects PSA not binding to a proteinase
      inhibitor. RESULTS: In serum samples, an 80-kD to 90-kD species of PSA in complex
      with alpha 1-antichymotrypsin is the predominant molecular form and a minor
      molecular form of serum PSA was an approximately 30-kD fraction not binding to a
      proteinase inhibitor. CONCLUSIONS: The benefits of detecting different molecular
      forms of serum PSA should be investigated regarding possibilities to facilitate
      differential diagnosis of carcinoma of the prostate (CAP) and benign prostatic
      hyperplasia (BPH).

PMID- 1376194
TI  - Pathology of carcinoma of the prostate.
AB  - In this presentation the authors review the pathology of prostatic carcinoma
      (PCa), and discuss criteria for pathologic diagnosis, premalignant lesions,
      lesions that simulate PCa, immunopathology, special types of PCa, effects of
      therapy on the prostate, and recent efforts to improve diagnostic and prognostic
      capabilities. The possible role of study of nucleolar organizing regions is
      reported. A new method for demonstration of chromosome in formalin-fixed,
      paraffin-embedded tissue is presented. The need for research in all aspects of
      pathology is emphasized.

PMID- 1376195
TI  - Critical assessment of prostate cancer staging.
AB  - Staging of prostatic adenocarcinoma is a systematic classification of the extent
      of disease based on clinical and pathologic criteria. This classification
      determines treatment and reflects ultimate expected clinical outcome. The
      technologic changes in diagnostic modalities need to be incorporated into the
      staging classification and a better assessment of biologic hazard of each
      individual tumor needs to be developed to further refine current treatment of
      prostate cancer.

PMID- 1376196
TI  - Benign prostatic hyperplasia. The scope of the problem.
AB  - BACKGROUND: The prevalence and incidence of clinical problems secondary to and
      associated with benign prostatic hyperplasia (BPH) are of increasing concern as
      the population ages. METHODS: Selected published reports using anatomical and
      clinical criteria to identify BPH and its clinical sequelae were reviewed.
      RESULTS: The following observations seem to reflect the current state of
      knowledge: (1) BPH develops with increasing frequency as men age; (2) BPH causes
      significant pathologic changes in the urinary tract of some patients and symptoms
      in others; and (3) other identifiable or cryptic etiologic factors may be the
      predominant cause of identical voiding dysfunction in patients with BPH.
      CONCLUSION: Essential information about factors initiating and promoting
      development of BPH, the exact mechanisms by which BPH alters voiding mechanisms,
      and definitive diagnostic criteria to establish the role of BPH in clinical
      changes are lacking. Progress in these problem areas is essential to guide
      appropriate clinical management.

PMID- 1376197
TI  - Indications for treatment of benign prostatic hyperplasia. The American
      Urological Association Study.
AB  - BACKGROUND: In 1990, a pilot study was begun that evaluated benign prostatic
      hyperplasia (BPH) at five clinical institutions. Data management and coordination
      of this study was performed at the Medical Practices Evaluation Center at
      Massachusetts General Hospital. Because of decreased patient enrollment, one
      institution was dropped. This was a randomized, prospective, clinical study that
      provided an initial overview of the trial and a rationale for the project.
      METHODS: Patients with clinically significant signs and symptoms of BPH were
      enrolled in this study. A symptom index consisting of seven items was used to
      document patient complaints of prostatic enlargement. Prostate size was
      determined using ultrasonography. Uroflowmetry (peak flow and mean flow) and
      residual urine volumes were documented. Abdominal ultrasonography was performed
      to rule out the presence of a dilated upper urinary tract. Cystoscopy was
      completed to determine the extent of prostatic and bladder neck obstruction.
      Trabeculations or cellules in the bladder, if present, were also documented.
      Conclusions. Preliminary results were obtained. The operative and nonoperative
      options depending on prostate size are shown in the figures of this article. The
      use of an interactive video disc has been beneficial in explaining the risks and
      benefits of each treatment option applicable to the patient in this randomized,
      controlled study.

PMID- 1376198
TI  - The clinical assessment of benign prostatic hyperplasia.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common pathologic
      condition to afflict the aging male and the second most common cause of surgical
      intervention in men older than 60 years of age. Unfortunately, many men currently
      undergo prostatectomy without rigorous evaluation of their condition in terms of
      either transition zone hyperplasia or the extent to which this is causing bladder
      outflow obstruction. METHODS: In this review, the importance of symptoms and
      symptom scoring systems associated with bladder outflow obstruction due to BPH
      were considered as well as the use of prostate specific antigen (PBS),
      uroflowometry, and abdominal and transrectal ultrasound studies in addition to
      magnetic resonance imaging (MRI). CONCLUSION: Patients undergoing surgical or non
      surgical treatment for BPH should be studied by means of a formal symptom score,
      as well as repeated uroflowometry and abdominal ultrasound. PSA determination
      should also be made and those patients with values above 4 mg/ml should undergo
      transrectal ultrasound study and biopsy. Patients with values greater than 10
      mg/ml should be considered for systematic biopsy whatever this reveals. MRI, with
      or without the new endorectal coil, is a promising tool for evaluation of the
      prostate, but more in a research than routine clinical context.

PMID- 1376199
TI  - The association of benign prostatic hyperplasia and cancer of the prostate.
AB  - There are a number of similarities between benign prostatic hyperplasia (BPH) and
      cancer. Both display a parallel increase in prevalence with patient age according
      to autopsy studies (86.2% and 43.6%, respectively, by the ninth decade), although
      cancer lags by 15-20 years. Both require androgens for growth and development,
      and both respond to antiandrogen treatment regimens. Most cancers arise in
      prostates with concomitant BPH (83.3%), and cancer is found incidentally in a
      significant number of transurethral prostatectomy (TURP) specimens (10%). The
      clinical incidence of cancer arising in patients with surgically treated BPH is
      approximately 3%. BPH may be related to a subset of prostate cancer which arises
      in the transition zone, perhaps in association with atypical adenomatous
      hyperplasia (AAH). It is important to exclude cancer in patients presenting with
      symptoms of bladder outlet obstruction presumably due to BPH. For such patients,
      we recommend digital rectal examination (DRE) and, at least in high-risk
      patients, serum prostate specific antigen (PSA) determination. Transrectal
      ultrasound (TRUS) should be employed in patients with elevated PSA levels to
      determine the volume of the prostate, the relative contribution of BPH to volume,
      and the PSA density (ratio of PSA level to volume). Biopsy should be obtained
      from any area suspicious for cancer. Early detection and treatment of cancer when
      it is localized offers the greatest chance for cure.

PMID- 1376200
TI  - Management of relapsing disease in prostate cancer.
AB  - Almost all patients with prostatic cancer will eventually escape the control of
      the first-line endocrine therapy and relapse. This escape is attributed to
      selecting and/or cloning preexisting or de novo appearing hormone-independent or
      resistant cell lines and occurs in most patients after a median time of 12 to 18
      months. Currently, there are no generally accepted rules for second-line
      management, either endocrine or by other means. It seems reasonable to consider
      length of survival as the only objective response criterion and not to rely on
      other response criteria. Available second-line therapeutic modalities in relapsed
      prostatic cancer are alternative endocrine manipulations, chemotherapy, combined
      endocrine and cytotoxic therapy, new drugs, radiation therapy, and general
      antitumoral and supportive care. Second-line therapy in relapsed disease makes
      sense if life can be prolonged while relieving symptoms and maintaining or
      improving the quality of survival. The capacity to prolong survival is limited.
      As a result, second-line therapy should aim more at improving the quality rather
      than the length of survival while considering the specific expectations and
      wishes of the patient.

PMID- 1376201
TI  - Surgical treatment of prostatic hyperplasia.
AB  - BACKGROUND: For more than seven decades prostates have been enucleated
      surgically, and for almost six decades they have been resected endoscopically.
      Results have been impressive and increasingly better, and the procedure has been
      reasonably safe. Variations to these two approaches have abounded and have made
      it safer, quicker, and easier, but never cheaper. METHODS: Currently, an
      abundance of alternatives have surfaced and for a variety of reasons. All
      alternatives share several shortcomings: results are not predictable, there is no
      tissue, and serendipitous prostate cancer could be missed. In addition, it may be
      categorically said that rarely does any of the alternatives achieve the
      effectiveness of prostatectomy that is appropriately indicated and properly
      performed. RESULTS: Urologists should participate in an objective assessment of
      the comparative merits and deficiencies of the variations of and alternatives to
      prostatectomy. Assessment of outcomes, safety, efficacy, and cost, as well as the
      development of guidelines, should continue. CONCLUSIONS: With our counsel and the
      government's reimbursement, the public will decide which alternatives are safe
      and reasonably effective and should survive.

PMID- 1376203
TI  - Nonsurgical, nonpharmacologic treatment of benign prostatic hyperplasia.
AB  - New treatment modalities are becoming available for benign prostatic hyperplasia.
      Permanent or temporary stenting of the prostatic urethra, balloon dilatation of
      the prostate, and hyperthermia and thermotherapy are in the forefront. None of
      the methods has found a definite place in the spectrum of indications.
      Prospective trials are needed to ascertain the safety, efficacy, and durability
      of results.

PMID- 1376202
TI  - Nonsurgical treatment of prostatic hyperplasia.
AB  - BACKGROUND: Epidemiologic studies in castrates strongly support the key role of
      the testis in the pathogenesis of benign prostatic hyperplasia (BPH). Since the
      testis secretes both androgen and estrogen, both of these hormones have been
      implicated in BPH. Many data support the important role of dihydrotestosterone
      (DHT) in BPH. It is now possible to quantify prostate size and function with
      reliable new techniques and to utilize androgen withdrawal studies to test the
      validity of the DHT theory. METHODS: A variety of androgen-blocking drugs have
      been demonstrated to decrease prostate size by approximately 30% by either
      blocking secretion of circulating testosterone and adrenal androgen, inhibiting 5
      alpha-reductase to prevent DHT formation, or blocking DHT binding to androgen
      receptors. RESULTS: Accompanying these changes in size have been significant
      improvement in clinical symptoms of prostatism in approximately 50% of patients
      when double-blind, large multicenter studies were conducted with one of these
      drugs. Although these results suggest a very important role for androgen,
      particularly dihydrotestosterone, in the pathogenesis of BPH, other abnormalities
      besides those of androgen metabolism may coexist since significant numbers of
      patients do not show a total reversal of disease. There is strong indirect
      evidence for a possible role for estrogen in the pathogenesis of BPH and studies
      are under way to test the effects of estrogen withdrawal on prostate size and
      symptoms. Similarly, dynamic aspects of prostatic obstruction, which are under
      alpha adrenergic regulation, may also be a component of this disease and amenable
      to therapy with alpha-adrenergic blockers. CONCLUSIONS: Therefore it would seem
      that BPH may be multifactorial and require combined therapy. Androgen would
      certainly appear to be necessary, but perhaps not sufficient, for the
      pathogenesis of this disorder.

PMID- 1376204
TI  - An American Urological Association prospective, randomized clinical trial in the
      treatment of benign prostatic hyperplasia.

PMID- 1376205
TI  - Detection and screening for prostate cancer.

PMID- 1376207
TI  - Report of the Committee on Staging and Pathology.

PMID- 1376206
TI  - Diagnosis and markers in prostate cancer.

PMID- 1376208
TI  - Relapsing disease.

PMID- 1376209
TI  - Scope of the problem. Indications for treatment and assessment of benign
      prostatic hyperplasia and its relationship to cancer.

PMID- 1376210
TI  - Surgical treatment for benign prostatic hyperplasia.

PMID- 1376211
TI  - Alternatives to surgery for benign prostatic hyperplasia.

PMID- 1376212
TI  - Human immunodeficiency virus type-1 (HIV-1) infection of endothelial cells in
      vitro: a virological, ultrastructural and immuno-cytochemical approach.
AB  - In an attempt to better understand the role of endothelial cells during HIV-1
      infection, we report a virological and ultrastructural study on isolated
      endothelial cells from human adipose tissue, infected by HIV-1 in vitro.
      Supernatants from cultures showed the presence of p24 antigen and reverse
      transcriptase activity starting two days after HIV inoculation. A significant
      decrease of viral rescue was observed in cycloheximide treated cells confirming a
      de novo synthesis of viral products. SEM analysis individualized several surface
      slender projections and interdispersed virus-like particles in the infected
      cells. Furthermore, transmission electron microscopy (TEM) results showed
      cellular aspects of HIV phagocytosis and virus budding, suggesting that
      endothelial cells may represent a CD4 negative cell target of HIV-1 infection.

PMID- 1376213
TI  - Nonsurgical restoration of pulsatile arterial flow.
AB  - Percutaneous transluminal angioplasty is an established method of
      revascularization in a variety of arterial stenotic conditions. When applied to
      specific morphologic and clinical indications, it can be very effective. It
      appears to be the procedure of choice for focal stenotic lesions of the iliac and
      femoropopliteal system. Its role in infrapopliteal atherosclerotic disease is
      less certain, but more optimistic, with recent reports. New methods for
      preventing restenosis and abrupt closure are currently being developed, and they
      appear to be promising as adjunctive therapy with mechanical catheter-directed
      intervention. The future of these adjunctive agents will likely improve the
      outcome and reduce the immediate failure rates of angioplasty. Other modalities,
      including thermal laser angioplasty and atherectomy, also appear to have a
      promising future. These methods, coupled with better endoluminal guidance, such
      as ultrasound, will help guide the interventional procedure more precisely and
      hopefully broaden the application and improve the outcome.

PMID- 1376214
TI  - The alpha-subunit of glycoprotein hormones exists in the prolactin secretory
      granules of the bullfrog (Rana catesbeiana) pituitary gland.
AB  - Our recent finding that the number of immunoreactive alpha-subunit cells was
      invariably greater than the total number of immunoreactive gonadotropin (GTH) and
      thyrotropin (TSH) cells in the bullfrog (Rana catesbeiana) pituitary gland raises
      the possibility that the alpha-subunit also exists in pituitary cells other than
      GTH and TSH cells. The present study demonstrates that there are a considerable
      number of immunoreactive prolactin (PRL) cells that are also stained with
      antibody against the alpha-subunit when adjacent sections are
      immunocytochemically examined. Neither immunoreactive growth hormone nor
      adrenocorticotropin cells are stained with the antibody against the alpha
      subunit. The specificity of the antibody against the alpha-subunit and of that
      against PRL was demonstrated by preabsorption test, non-competitive binding test,
      and immunoblot analysis. Double-immunolabeling with gold particles of different
      sizes for the alpha-subunit and PRL revealed that most of the immunolabeled PRL
      secretory granules are also labeled with the alpha-subunit antibody. The gold
      particles indicating the presence of the alpha-subunit were mostly found in the
      peripheral zone of the secretory granules.

PMID- 1376215
TI  - Immunohistochemical localization of keratin in bull, goat, and sheep anterior
      pituitary glands.
AB  - Immunohistochemical localization of keratin, an intermediate filament protein,
      was studied in bull, goat, and sheep anterior pituitary glands, i.e., in animals
      of the order Artiodactyla. Strong immunoreactivity was detected in the cells of
      the marginal layer of bull and goat, as well as in cysts or large follicles in
      the anterior lobe of all 3 species. In addition, a number of stellate-shape cells
      were immunoreactive for keratin and were distributed throughout the anterior
      lobe. The localization of keratin-positive cells in light-microscopic
      preparations correlated precisely with the localization of folliculo-stellate
      cells in adjacent ultrathin sections. In ultrastructural studies, many slender
      and elliptical membranous components which were different from smooth endoplasmic
      reticulum were observed in the cytoplasm of the some keratin-positive cells. Some
      of the folliculo-stellate cells in the 3 species were also immunoreactive for the
      alpha subunit of S-100 protein, which exists in some epithelial cells. On the
      other hand, immunolocalization of glial fibrillary acidic protein, a glial cell
      marker, could not be demonstrated in the anterior pituitary glands of the 3
      species studied. These results suggest that keratin-positive folliculo-stellate
      cells express epithelial-like characteristics.

PMID- 1376217
TI  - Bleomycin lung: the effect of different chemotherapeutic regimens.
AB  - A review of hard-copy computed tomography (CT) images of patients who had
      undergone chemotherapy for testicular teratoma revealed that the incidence of
      lung toxicity appeared to be lower in those who had received bleomycin by slow
      infusion [EBCi (3) regimen, etoposide/bleomycin/cisplatin] rather than by
      intravenous bolus [PVB regimen, cisplatin/vinblastine/bleomycin; BEP (5) regimen,
      bleomycin/etoposide/cisplatin]. This difference reached statistical significance
      only for PVB vs EBCi (3) (t = 2.63, P less than 0.01). Nevertheless, in view of
      continuing reports of mortality resulting from bleomycin-induced pulmonary
      fibrosis in patients receiving the drug by i.v. bolus, further exploration of
      these results is clearly justified.

PMID- 1376218
TI  - Production of thyroid tumours in mice by demethylating agents.
AB  - Previous studies on thyroid tumorigenesis in rodents have explored the role of
      oncogene mutation in tumour development. However, many mutagens are also known to
      decrease DNA methylation, another factor known to be important in the regulation
      of gene expression. We report the results of a small study to examine whether the
      demethylating agents 5-azacytidine and 5-aza-2-deoxycytidine could promote
      radiation- or goitrogen-induced tumorigenesis in the mouse, and whether they
      could potentiate the effect of a combined radiation and goitrogen regime. Three
      single doses of either 5-azacytidine or 5-aza-2-deoxycytidine increased the
      frequency of lesions in the goitrogen-treated animals; one of these lesions was a
      metastasising carcinoma. Thyroid carcinomas are very rare in mice in the absence
      of mutagen treatment, and metastasis is particularly unusual. There was no
      significant difference, at the dosages used, between the number of tumours
      induced by demethylating agents and those induced by a mutagen (radiation) in
      goitrogen-treated animals. Unlike goitrogens, demethylating agents did not
      promote radiation-induced tumorigenesis, and they did not produce any significant
      potentiation of the conventional regime of radiation and goitrogen at the dosages
      used. This study suggests that the role of non-genotoxic factors, such as agents
      affecting patterns of DNA methylation, warrants consideration in thyroid
      tumorigenesis.

PMID- 1376216
TI  - Expression of vimentin by rabbit corneal epithelial cells during wound repair.
AB  - Intermediate filaments of epithelial cells generally consist of specific
      combinations of keratins. However, cultured epithelial cells from certain tissues
      and some epithelial tumors have been shown also to express vimentin. In the
      present study, the expression of vimentin by epithelial cells in healing corneal
      wounds (partial thickness penetrating wounds) and in tissue culture was analyzed.
      Both immunohistochemical and immunotransblot analyses indicated that although
      vimentin was not detected in the normal rabbit corneal epithelium in vivo,
      cultured rabbit corneal epithelial cells co-express keratins and vimentin. At 1
      day post-wounding, vimentin was not detectable in the epithelial cells that had
      covered the denuded stroma. However, at 2 days postwounding, the epithelium at
      the base of the epithelial plug immunoreacted with both anti-vimentin and
      antikeratin monoclonal antibodies. Immunotransblot analyses of the extracts of
      the epithelial plugs confirmed the presence of vimentin (Mr = 58k). The 58k band
      was not detected in the extract of normal rabbit corneal epithelium. At day/5,
      vimentin was no longer detectable in the epithelium. This study demonstrated that
      corneal epithelial cells transiently co-express vimentin and keratins in vivo
      during wound healing and in tissue culture. The time-course of the transient
      expression of vimentin suggests that the vimentin expression in the epithelial
      cells during healing is not linked to cell proliferation or to the centripetal
      migration of the epithelium during early stages (first 24 h) of healing, but may
      be linked to cell-matrix interactions or the migration of basal cells in the
      upward direction at the following stage of healing.

PMID- 1376219
TI  - A monoclonal antibody distinguishes anterior horn cells of human embryonic spinal
      cord during a transient period of development.
AB  - Monoclonal antibodies were prepared by using the anterior horn region of human
      embryonic spinal cord as immunogen. To increase the specificity of the immune
      response towards the anterior horn cells, mice were first injected with antigens
      from the posterior horn and then immunosuppressed with cyclophosphamide;
      subsequently antigens from the anterior horn were injected. One of the monoclonal
      antibodies recognizes a small population of anterior horn cells of human
      embryonic spinal cord during a transient period of development (9-10th embryonic
      week); these cells are probably motoneurons according to their location in the
      spinal cord, their positive staining for acetylcholinesterase and their large
      nuclei. The staining pattern has a special axial distribution as it is limited to
      the cervical and thoracic regions of the spinal cord. The antibody is species
      specific and shows a high degree of tissue specificity. Since this antibody
      distinguishes a small group of anterior horn cells in the spinal cord during a
      specific developmental stage, it opens stimulating perspectives for further
      investigation on the nature of the antigen and its putative role during the
      development of the human embryonic spinal cord.

PMID- 1376220
TI  - Immunocytochemical expression of the endothelial barrier antigen (EBA) during
      brain angiogenesis.
AB  - The antibody to the endothelial barrier antigen (anti-EBA) is localized to the
      luminal plasma membrane of endothelia that have a blood-brain barrier (BBB) but
      not to other vessels, for instance those in the circumventricular organs, which
      lack barrier function. We have examined EBA expression in the rat in certain
      tissues and in brain microvessels in models of brain angiogenesis such as
      development, wound healing and neural transplantation. All brain microvessels
      including pial ones stained for anti-EBA whereas those of the dura, median
      eminence and choroid plexus did not. Vessels of the iris which are characterized
      by tight junctions and barrier function expressed EBA strongly. Embryonic day 18
      brain did not stain at all for anti-EBA although vessels were readily localized
      with anti-laminin. Following stab wounds to mature brain, directly injured and
      adjacent microvessels lacked EBA expression for a period of approximately 2 weeks
      which is a similar time frame of BBB breakdown. Following this period, EBA
      expression gradually returned to a normal pattern by 3-4 weeks. Likewise, in
      intraparenchymal transplants of fetal neocortex EBA expression was not observed
      for 2 weeks and while at later times transplant vessels expressed EBA whereas
      some interface vessels associated with inflammatory cells did not. Permeable
      choroid plexus vessels vascularizing intraventricular transplants did not stain
      for anti-EBA at any time period and neither did vessels in adrenal medulla
      transplants. The present study shows that while EBA expression is a postnatal
      event unlike the development of a barrier to serum protein, its expression may be
      lost or delayed in injured vessels or ones associated with inflammatory cells or
      reactive astrocytes.

PMID- 1376221
TI  - Regulated splicing of the amyloid precursor protein gene during postnatal
      development of the rat basal forebrain.
AB  - The expression of the amyloid precursor protein (APP) gene has been examined in
      the basal forebrain of rats from birth to adulthood. Levels of total APP mRNA are
      highest at birth and at postnatal day 15 (P15). The most abundant transcript in
      rat brain is APP-695, whose expression has previously been found to be largely
      restricted to the central nervous system. Comparison of the developmental
      profiles of APP-695 mRNA with that of Kunitz-protease inhibitor (KPI)-containing
      APP mRNA shows that the greatest difference in expression occurs at P15, when APP
      695 message levels are over 6-fold higher than KPI-containing APP mRNA (APP-751,
      APP-770). This is the largest difference in the APP-695/KPI-APP ratio observed
      during postnatal development and coincides with the period of maximal
      neurotrophic responsiveness in the basal forebrain. These results suggest that
      the APP gene is alternatively spliced during postnatal development and that
      regulated expression of APP-695 may be influenced by neurotrophic factors in
      vivo.

PMID- 1376223
TI  - No correlation between reticulocyte count and erythroblast count.

PMID- 1376222
TI  - Immunohistochemical localization of basal lamina components in the developing rat
      epiphyseal cartilage canals.
AB  - The purpose of this study was to investigate the relationship between the
      appearance of basal lamina components (Type IV collagen and laminin) and the
      development of cartilage canals. In the distal femoral epiphyses from developing
      rats, the distribution of basal lamina components in the cartilage canal was
      examined immunohistochemically. The formation of cartilage canals from the
      perichondrium was first observed on the fifth day after birth. By Day 8, a few
      cartilage canals penetrated the epiphyseal cartilage and considerably increased
      in size and length. By light microscopic immunohistochemistry, reticular
      structures stained with anti-Type IV collagen and antilaminin antibodies were
      observed in the cartilage canals. In the early development of cartilage canals,
      however, immunostaining by anti-Type IV collagen antibodies was weaker than that
      by antilaminin antibodies. In eight-day-old rats, the laminin-positive reticular
      structures were more densely colored and more widely distributed in the canal
      than the Type IV collagen-positive ones. Type IV collagen was found around the
      endothelial cells of the developing capillaries by electron microscopic
      immunohistochemistry. Laminin was observed in the cytoplasm of the mesenchymal
      fibroblastic cells and their pericellular matrix as well as in the capillary
      basal lamina. These immunohistochemical electron microscopic observations can
      explain the differences that are observed in Type IV collagen and laminin
      immunostaining patterns as cartilage canals develop. Laminin synthesized by the
      mesenchymal fibroblastic cells may promote the migration and the outgrowth of
      endothelial cells in the formation of cartilage canals.

PMID- 1376224
TI  - Retroviral reverse transcriptases: error frequencies and mutagenesis.

PMID- 1376225
TI  - Tracing the origin of retroviruses.
AB  - Reverse transcriptase sequences, which are fundamental to retrovirus existence,
      are widely distributed in the living world. Phylogenies based on their sequences
      set vertebrate retroviruses apart as relatively modern creations. Their nearest
      evolutionary relatives are a large group of transposable elements that have all
      the standard retrovirus equipment except spliced envelope proteins. The
      distribution of these elements suggests a long-standing presence predating the
      radiation of plants, fungi, and animals. There is another large group of
      elements, LINEs, that also contain recognizable reverse transcriptase sequences
      and which likely diverged even earlier, as evidenced by their presence in
      trypanosomes and other protists. They lack tRNA priming sites--which they could
      have lost--but they do exhibit characteristic eukaryotic polyadenylation. These
      elements are problematic in that the sequences are so degenerate in most
      instances that it is not possible to identify the accessory enzymes or structural
      proteins with any confidence, leaving major gaps in our reconstruction of events.
      Even with these gaps, however, the historical beginnings of retroviruses can be
      traced back to events coincident with the prokaryotic invasion of primitive
      eukaryotes.

PMID- 1376226
TI  - Fat embolism syndrome and pulmonary microvascular cytology.
AB  - Pulmonary microvascular cytology consists of analysis of capillary blood sampled
      while a Swan-Ganz catheter is in the wedge position. This technique has proved to
      be useful in the diagnosis of lymphangitic spread of carcinoma in the lungs and
      there are case reports of their use in amniotic fluid embolism. Its usefulness in
      diagnosing fat embolism syndrome has been shown only rarely. We report a new case
      in which pulmonary microvascular cytologic study allowed a definite diagnosis of
      fat embolism syndrome. We suggest obtaining routinely samples of capillary blood
      when a pulmonary catheter is in place and fat embolism is suspected on a clinical
      basis.

PMID- 1376228
TI  - The representation of extendedness in children's drawings of sticks and discs.
AB  - Piaget has suggested that the reason why children find it difficult to draw
      foreshortened views is because they lack any conscious awareness of their own
      viewpoint. Instead, it is proposed that most of these difficulties derive from
      the constraints of drawing as a representational system: for example, although a
      round region shows a true view of a foreshortened stick, it is unsatisfactory as
      a representation. To test between these alternative proposals, 4-, 7-, and 12
      year-olds were asked to draw sticks and discs in foreshortened and
      nonforeshortened positions. As predicted, fewer 7- and 12-year-olds used a round
      region to represent a foreshortened stick, compared with children of the same age
      who used a long region to represent a foreshortened disc. In addition, the 12
      year-olds used a different and more effective denotation system compared with the
      7-year-olds.

PMID- 1376227
TI  - Obstructing endobronchial bands complicating radiation therapy for lung
      carcinoma.
AB  - A 57-year-old man with small cell lung carcinoma developed benign, obstructing
      endobronchial bands five months after external beam radiation therapy. We believe
      that this represents an unusual delayed complication of radiation therapy for
      airway tumors. An excellent clinical response was obtained after laser ablation
      of the lesion.

PMID- 1376229
TI  - [Protection from the effect of cadmium chloride of human cells, pretreated with
      vitamins, interferon and preliminary low-dose gamma irradiation].

PMID- 1376230
TI  - Effects of short-term inhalation exposure to 1-nitropropane and 2-nitropropane on
      rat liver enzymes.
AB  - Male Sprague-Dawley rats were exposed to vapors of 1-nitropropane (1-NP) and 2
      nitropropane (2-NP) at air concentrations of 100 ppm for 7 hours per day on four
      consecutive days. Livers were analyzed for enzymatic activities after 1-, 2-, and
      4-day inhalation periods. Liver microsomal cytochrome P450 was depressed by 2-NP
      and elevated following exposure to 1-NP. Levels of cytochrome b5 were slightly
      increased in rats exposed to 1-NP and remained unchanged after inhalation of 2
      NP. Total glutathione (GSH), GSH S-transferase, and UDP-glucuronosyltransferase
      activities were enhanced by 2-NP. 1-NP induced GSH peroxidase while 2-NP did not.
      Glutathione reductase was not altered after exposure to either isomer. No changes
      in the microsomal malondialdehyde content as a measure of lipid peroxidation and
      in the levels of serum aspartate transferase and serum glutamic oxaloacetic
      transaminase were observed during a 4-day exposure period in either of the
      exposed groups compared to control animals.

PMID- 1376231
TI  - Influence of solubility in lipid on bioconcentration of hydrophobic compounds.
AB  - Superhydrophobic compounds (log K(ow) greater than 6) do not bioconcentrate as
      much as predicted from the extrapolation of linear relationships between the
      logarithms of the bioconcentration factor (KB) and the octan-1-ol/water partition
      coefficient (K(ow)) developed for compounds with log K(ow) from 2 to 6.
      Statistical analysis of the literature data on solubility in lipid for 79
      hydrophobic compounds demonstrated a decrease in lipid solubility with increasing
      K(ow) values for superhydrophobic compounds. A similar, but more significant,
      relationship was obtained for the chlorinated hydrocarbons which closely
      corresponded with effectively the same relationship derived from fish
      bioconcentration data. As a result it is suggested that an important factor
      contributing to the lower than expected bioconcentration exhibited by
      superhydrophobic compounds is their relatively low solubility in lipid not
      reflected by the K(ow) value. It is suggested that lipid/water partition
      coefficients would provide more accurate descriptors of the bioconcentration
      process.

PMID- 1376232
TI  - Amelioration by BAL (2,3-dimercapto-1-propanol) and DMPS (sodium 2,3-dimercapto-1
      propanesulfonic acid) of arsenite developmental toxicity in mice.
AB  - Inorganic arsenic is embryotoxic and teratogenic in chicks, golden hamsters,
      mice, and rats. Certain dithiol chelators have been reported to protect against
      arsenite-induced lethality and to decrease arsenic body burden. The present study
      evaluated the influence of BAL (2,3-dimercapto-1-propanol) and DMPS (sodium 2,3
      dimercapto-1-propanesulfonic acid), a water-soluble analogue of BAL, on arsenic
      induced embryotoxic and teratogenic effects in the mouse. A series of four BAL or
      DMPS injections was administered sc to pregnant mice immediately after a single
      ip injection of 12 mg/kg of sodium arsenite given on Day 9 of gestation and at
      24, 48, and 72 hr thereafter. Controls received sc corn oil with or without
      arsenite. Amelioration by BAL and DMPS of arsenite developmental toxicity was
      assessed at 15, 30, and 60 mg/kg/day, and 75, 150, and 300 mg/kg/day,
      respectively. BAL given following arsenite was not able to ameliorate the
      developmentally toxic effects of arsenite seen in mice, whereas treatment with
      DMPS at 150 and 300 mg/kg showed significant protective effects against arsenite
      embryotoxicity and teratogenicity. DMPS administration at 300 mg/kg also
      protected the dams against arsenite-induced maternal toxicity.

PMID- 1376233
TI  - Copper-induced hepatic ultrastructural alterations in the snake-headed fish,
      Channa punctatus.
AB  - Ultrastructural alterations in the liver of the snake-headed fish (Channa
      punctatus) following short-term exposure to 0.05 and 0.1 mg/liter of Cu were
      investigated by means of transmission electron microscopy. The changes consisted
      of extensive proliferation of the smooth endoplasmic reticulum and dilation of
      the rough endoplasmic reticulum, suggesting an active detoxification attempt by
      the liver. Mitochondrial degenerative changes such as loss of normal material
      density, cristae, or outer or inner membranes with mitochondrial swelling were
      also observed after Cu intoxication. An increase in the numbers of lysosomes and
      electron dense bodies was examined. Granular chromatin and electron dense
      accumulation were observed in the nucleus at 0.05 mg/liter of Cu after 4 days of
      exposure. Cytoplasmic debris in the hepatocyte cells became a frequent finding
      after 7 days of 0.05 mg/liter Cu treatment. More prominent alterations in
      hepatocytes were recorded at 0.1 mg/liter of Cu after 4 and 7 days of exposure. A
      highly dilated endoplasmic reticulum and shortened and reduced mitochondria were
      the prominent features of acute Cu toxicity. Nuclei of the necrotic cells showed
      marked clumping of chromatin with the aggregation of interchromatin material at
      the center of the nucleus. In some hepatocytes, bilobed nuclei with dilated
      nuclear membranes were also observed. The nucleoplasm of many cells showed
      continuity with the cytoplasm due to loss of nuclear inner and outer membranes. A
      comparison of liver pathology with that of other fish species and mammals has
      been attempted. The relationship of these cellular changes with the possible mode
      of action of Cu at cellular and subcellular levels is discussed.

PMID- 1376234
TI  - Short- and long-term effects of copper on the rosy barb (Puntius conchonius
      Ham.).
AB  - The rosy barb (Puntius conchonius) was exposed to copper (Cu) for short (48 hr)
      and long (8 weeks) terms and effects on enzyme activities and biochemical
      variables in the blood and tissues were examined. In vivo exposure to 571
      micrograms CuSO4/liter (96-hr median tolerance limit (TLm)) for 48 hr stimulated
      to varying degrees acid phosphatase (AcP), alkaline phosphatase (AlP) (except in
      the liver), and acetylcholinesterase activities in selected tissues. The alanine
      aminotransferase and lactic dehydrogenase (LDH) (except in the heart) activities
      were inhibited to varying degrees in vivo. In vitro, the presence of 10(-6) M Cu
      suppressed enzyme activities in the tissues examined, with a few exceptions such
      as AcP in ovaries and gut, AlP in liver, gills, gut, and testes, and LDH in
      liver. Hyperglycemia, hyperlactemia, hyperproteinemia, elevated blood free fatty
      acid (FFA) levels, and hypocholesterolemia were manifested in the fish exposed to
      190 micrograms CuSO4/liter (1/3 96-hr TLm). Effects on the tissues included
      glycogenolysis (liver and skeletal muscles), glycogenesis (brain and heart), a
      marked rise in hepatic proteins, accumulation of FFAs in liver and skeletal
      muscles, and reduction in hepatic and gonadal cholesterol contents. After 8
      weeks, a trend toward recovery was noted in the biochemical variables (except
      blood and hepatic protein levels).

PMID- 1376235
TI  - Copper tolerance and copper accumulation of herbaceous plants colonizing inactive
      California copper mines.
AB  - Herbaceous plant species colonizing four copper mine waste sites in northern
      California were investigated for copper tolerance and copper accumulation. Copper
      tolerance was found in plant species colonizing soils with high concentrations of
      soil copper. Seven of the eight plant species tested were found at more than one
      copper mine. The mines are geographically isolated, which makes dispersal of
      seeds from one mine to another unlikely. Tolerance has probably evolved
      independently at each site. The nontolerant field control population of Vulpia
      microstachya displays significantly higher tolerance to copper at all copper
      concentration levels tested than the nontolerant Vulpia myrous population, and
      the degree of copper tolerance attained by V. microstachya at the two copper
      mines was much greater than that found in V. myrous. It suggests that even in
      these two closely related species, the innate tolerance in their nontolerant
      populations may reflect their potential for evolution of copper tolerance and
      their ability to initially colonize copper mine waste sites. The shoot tissue of
      the copper mine plants of Arenaria douglasii, Bromous mollis, and V. microstachya
      accumulated less copper than those plants of the same species from the field
      control sites when the two were grown in identical conditions in nutrient
      solution containing copper. The root tissue of these mine plants contain more
      copper than the roots of the nonmine plants. This result suggests that exclusion
      of copper from the shoots, in part by immobilization in the roots, may be a
      feature of copper tolerance. No difference in the tissue copper concentration was
      detected between tolerant and nontolerant plants of Lotus purshianus, Lupinus
      bicolor, and Trifolium pratense even though the root tissue had more copper than
      the leaves. It suggests that copper tolerance in these legume species is not due
      to a mechanism of differential capacity for copper accumulation in the roots.
      Different mechanisms of copper tolerance may have evolved among the plant species
      colonizing the northern California copper mine waste sites.

PMID- 1376236
TI  - Germination of seeds from an irradiated forest: implications for waste disposal.
AB  - Jack pine (Pinus banksiana Lamb.) retain their seeds from year to year, so that
      in an irradiated forest, each tree receives a specific dose rate but has seeds
      that have accumulated a range of total doses. The Field Irradiator-Gamma facility
      in Pinawa, Manitoba, contains jack pine that have been irradiated longer and at
      lower dose rates than previously reported. Seed germination and germination rate
      were examined on seeds irradiated on the parent tree for up to 5 years.
      Germination rate was most sensitive and showed deleterious effects at 1.1 mGy hr
      1. This is not much lower than results reported by others in shorter-term
      studies. Effects were related to dose rate rather than total dose. Hormesis,
      indicated by statistically significant increased germination rate, was evident at
      0.6 mGy hr-1. To put these results into context, the concentrations of selected
      radionuclides that, through internal contamination, would deliver 1.1 mGy hr-1 to
      plants were estimated. For 99Tc and 129I, these concentrations are far above the
      chemical toxicity thresholds for plants. Clearly, as assessments of waste
      repositories begin to consider effects on organisms other than humans, such as
      plants, chemical toxicity will be an important feature.

PMID- 1376238
TI  - Sediment pore water toxicity identification in the lower Fox River and Green Bay,
      Wisconsin, using the Microtox assay.
AB  - Microtox assays with two different methods of osmotic adjustment were used to
      assess the toxicity of pore waters from 13 sediment samples collected from the
      Fox River watershed in Wisconsin. No toxicity was observed in Microtox assays
      osmotically adjusted with NaCl; however, 15-min EC50 values for assays
      osmotically adjusted with sucrose ranged from 52 to 63% pore water. Un-ionized
      ammonia accounted for a large part of the observed toxicity, but, based on a
      toxic units approach, did not account for all observed toxicity. Metals (Cu, Zn)
      and an unidentified compound(s) may potentially contribute to the observed
      effects in Microtox assays osmotically adjusted with sucrose. The use of
      alternative osmotic adjustment techniques in the Microtox assay is one
      potentially useful tool for elucidating several classes of compounds responsible
      for effects observed in toxicity assays.

PMID- 1376237
TI  - Relative potency estimates of acceptable residues and reentry intervals after
      nerve agent release.
AB  - In the event of an unplanned release of a chemical warfare agent during any stage
      of the Chemical Stockpile Disposal Program, the potential exists for off-post
      contamination of drinking water, forage crops, grains, garden produce, and
      livestock. The more persistent agents, such as the organophosphate nerve agent
      VX, pose the greatest human health concern for reentry. A relative potency
      approach comparing the toxicity of VX to organophosphate insecticide analogues is
      developed and used to estimate allowable residues for VX in agricultural products
      and reentry intervals for public access to contaminated areas. Analysis of
      mammalian LD50 data by all exposure routes indicates that VX is 10(3) to 10(4)
      times more toxic than most commercially available organophosphate insecticides.
      Thus, allowable residues of VX could be considered at concentration levels 10(3)
      to 10(4) lower than those established for certain insecticides by the U.S. EPA.
      Evaluation of reentry intervals developed for these organophosphate analogues
      indicate that, if environmental monitoring cannot reliably demonstrate acceptable
      levels of VX, restricted access to suspect or contaminated areas may be on the
      order of weeks to months following agent release. Planning for relocation, mass
      care centers, and quarantine should take this time period into account.

PMID- 1376239
TI  - Microtox EC50 values for drinking water by-products produced by ozonolysis.
AB  - The aim was to determine the Microtox EC50 values of some aliphatic aldehydes and
      carboxylic acids of normal chain length with 1-14 carbon atoms since these
      compounds have been detected as ozonolysis by-products in drinking water. The
      aqueous EC50 values decreased with increasing chain length except for
      formaldehyde and for the C1-C7 acids. At chain lengths above C7, where methanolic
      saline solutions were utilized to promote solubility, the aldehydes were more
      toxic than their corresponding carboxylic acids. Below a chain length of C7, the
      reverse situation applied. More precise and sensitive EC50 values were observed
      at 15 and 25 min than at 5 min. Both C14 aldehyde and acid as well as palmitoleic
      acid showed luminescence in methanolic saline solutions. The C14 compounds are
      known natural substrates for bacterial luciferase, and the present findings
      confirm this for Photobacterium phosphoreum. The concentrations of the aldehyde
      and/or carboxylic acid ozonolysis by-products reported in drinking water could
      not be detected by the Microtox test. This is the first report of Microtox EC50
      values for these carboxylic acids and for aldehydes of chain lengths greater than
      C4.

PMID- 1376240
TI  - Effects of the herbicides hexazinone and triclopyr ester on aquatic insects.
AB  - Experiments were conducted to measure acute lethal response of aquatic insects to
      hexazinone (Velpar L) and triclopyr ester (Garlon 4) in flow-through laboratory
      bioassays, and to determine lethal and behavioral effects of these herbicides on
      insects in outdoor stream channels. No significant mortality (chi 2 P greater
      than 0.05) occurred in 13 test species exposed to hexazinone in laboratory flow
      through bioassays (1-hr exposure, 48-hr observation) at the maximum test
      concentration of 80 mg/liter. The survival of insects exposed to 80 mg/liter
      hexazinone in outdoor stream channels was likewise unaffected. Significant drift
      (chi 2 P less than 0.001) of Isonychia sp. occurred during a hexazinone treatment
      of the stream channels, but only at the maximum concentration of 80 mg/liter, and
      survival of the displaced Isonychia sp. was not affected. In flow-through
      bioassays with triclopyr ester, 10 of 12 test species showed no significant
      mortality at concentrations greater than 80 mg/liter. Survival of Isogenoides sp.
      and Dolophilodes distinctus was significantly affected at less than 80 mg/liter.
      Lethal concentrations were estimated by probit analysis of concentration-response
      data (1-hr exposure, 48-hr observation) for Simulium sp. (LC50 = 303 mg/liter),
      Isogenoides sp. (LC50 = 61.7 mg/liter), and D. distinctus (LC50 = 0.6 mg/liter).
      Triclopyr ester applications to the stream channels resulted in significant drift
      and mortality of D. distinctus at 3.2 mg/liter (no effects at 0.32 mg/liter),
      Isogenoides sp. at 32 mg/liter, and Hydropsyche sp. and Epeorus vitrea at 320
      mg/liter. The risk to aquatic insects of these herbicides used in forest
      vegetation management is discussed.

PMID- 1376241
TI  - Nobel Lecture. Elementary steps in synaptic transmission revealed by currents
      through single ion channels.

PMID- 1376242
TI  - Point mutations affecting antagonist affinity and agonist dependent gating of
      GABAA receptor channels.
AB  - Two variant amino acid sequences, which differ in a single amino acid residue,
      have been reported for the alpha 1-subunit of the rat brain GABAA receptor. We
      separately co-expressed these two variants in Xenopus oocytes, in combination
      with beta 2 and gamma 2. This experiment showed that substitution of alpha 1
      Phe64 by Leu strongly decreases the apparent affinity for GABA dependent channel
      gating from 6 microM to 1260 microM. Starting from this observation, we used in
      vitro mutagenesis to obtain information relevant for the localization of the
      agonist/antagonist binding site in the GABAA receptor. Homologous mutation in
      alpha 5 had similar consequences for alpha 5 beta 2 gamma 2. Homologous mutation
      in beta 2 and gamma 2 resulted in intermediate and small shifts in EC50,
      respectively. The apparent affinities of the competitive antagonists bicuculline
      methiodide and SR95531, the latter sharing close structural similarity with the
      agonist GABA, were decreased 60- to 200-fold by these mutations in alpha
      subunits. Interestingly, these affinities remained nearly unaffected upon
      introduction of the homologous mutations in beta 2 and gamma 2, or upon mutation
      of the neighbouring amino acid in alpha 1, Phe65 to Leu. These results suggest
      close functional and structural association of alpha-subunits with the
      agonist/antagonist binding site, and involvement of N-terminal portions of the
      extracellular domains of all subunits in the gating of the channel.

PMID- 1376243
TI  - Agonist pharmacology of neonatal and adult glycine receptor alpha subunits:
      identification of amino acid residues involved in taurine activation.
AB  - The inhibitory glycine receptor (GlyR) is a pentameric chloride channel protein
      which mediates postsynaptic inhibition in the mammalian central nervous system.
      In spinal cord, different GlyR isoforms originate from the sequential expression
      of developmentally regulated variants of the ligand binding alpha subunit. Here,
      neonatal alpha 2 and adult alpha 1 subunits are shown to generate GlyRs with
      distinct agonist activation profiles upon heterologous expression in Xenopus
      oocytes. Whereas alpha 1 receptors are efficiently gated by beta-alanine and
      taurine, alpha 2 GlyRs show only a low relative response to these agonists, which
      also display a reduced sensitivity to inhibition by the glycinergic antagonist
      strychnine. Construction of an alpha 2/alpha 1 subunit chimera and site-directed
      mutagenesis of the extracellular region of the alpha 1 sequence identified amino
      acid positions 111 and 212 as important determinants of taurine activation. Our
      results indicate the existence of distinct subsites for agonists on alpha 1 and
      alpha 2 GlyRs and suggest that the ligand binding pocket of these receptor
      proteins is formed from discontinuous domains of their extracellular region.

PMID- 1376244
TI  - Stable and functional expression of the calcium channel alpha 1 subunit from
      smooth muscle in somatic cell lines.
AB  - Voltage-activated calcium channels are membrane spanning proteins that allow the
      controlled entry of Ca2+ into the cytoplasm of cells. The principal channel
      forming subunit of an L-type calcium channel is the alpha 1 subunit. Transfection
      of Chinese hamster ovary (CHO) cells with complementary DNA encoding the calcium
      channel alpha 1 subunit from smooth muscle led to the expression of functional
      calcium channels which bind calcium channel blockers and show the voltage
      dependent activation and slow inactivation and unitary current conductance
      characteristic of calcium channels in smooth muscle. The currents mediated by
      these channels are sensitive towards dihydropyridine-type blockers and agonists
      indicating that the calcium channel blocker receptor sites were present in
      functional form. The smooth muscle alpha 1 subunit cDNA alone is sufficient for
      stable expression of functional calcium channels with the expected kinetic and
      pharmacological properties in mammalian somatic cells.

PMID- 1376245
TI  - Mitogen activated protein (MAP) kinase transforms tau protein into an Alzheimer
      like state.
AB  - The microtubule-associated protein tau is a major component of the paired helical
      filaments (PHFs) observed in Alzheimer's disease brains. The pathological tau is
      distinguished from normal tau by its state of phosphorylation, higher apparent
      M(r) and reaction with certain antibodies. However, the protein kinase(s) have
      not been characterized so far. Here we describe a protein kinase from brain which
      specifically induces the Alzheimer-like state in tau protein. The 42 kDa protein
      belongs to the family of mitogen activated protein kinases (MAPKs) and is
      activated by tyrosine phosphorylation. It is capable of phosphorylating Ser-Pro
      and Thr-Pro motifs in tau protein (approximately 14-16 P1 per tau molecule). By
      contrast, other proline directed Ser/Thr kinases such as p34(cdc2) combined with
      cyclin A or B have only minor effects on tau phosphorylation. We propose that MAP
      kinase is abnormally active in Alzheimer brain tissue, or that the corresponding
      phosphatases are abnormally passive, due to a breakdown of the normal regulatory
      mechanisms.

PMID- 1376247
TI  - The acidic transcriptional activator GAL-VP16 acts on preformed template
      committed complexes.
AB  - The action of the chimeric acidic transcriptional activator GAL-VP16 has been
      investigated by performing a series of kinetic experiments using the detergent
      Sarkosyl as well as monoclonal antibodies which specifically inhibit GAL-VP16 DNA
      binding and transcriptional activation. GAL-VP16 binds to recognition site
      rapidly, remains bound after transcriptional initiation and is required to
      maintain stimulated levels of reinitiation. GAL-VP16 action, which appears to
      result in an increase in the number of preinitiation complexes formed, occurs
      after the formation of template-committed complexes composed of promoter-bound
      TFIIA (STF) and a partially purified TFIID fraction conferring GAL-VP16
      responsiveness on a reconstituted basal transcription system. This TFIID fraction
      cannot be replaced by TFIIB or cloned TFIID. Our results suggest that GAL-VP16
      activates step(s) in preinitiation complex assembly occurring after TFIID has
      bound.

PMID- 1376246
TI  - Cloning by functional complementation of a mouse cDNA encoding a homologue of
      CDC25, a Saccharomyces cerevisiae RAS activator.
AB  - In the yeast Saccharomyces cerevisiae genetic and biochemical evidence indicates
      that the product of the CDC25 gene activates the RAS/adenylyl cyclase/protein
      kinase A pathway by acting as a guanine nucleotide protein. Here we report the
      isolation of a mouse brain cDNA homologous to CDC25. The mouse cDNA, called
      CDC25Mm, complements specifically point mutations and deletion/disruptions of the
      CDC25 gene. In addition, it restores the cAMP levels and CDC25-dependent glucose
      induced cAMP signalling in a yeast strain bearing a disruption of the CDC25 gene.
      The CDC25Mm-encoded protein is 34% identical with the catalytic carboxy terminal
      part of the CDC25 protein and shares significant homology with other proteins
      belonging to the same family. The protein encoded by CDC25Mm, prepared as a
      glutathione S-transferase fusion in Escherichia coli cells, activates adenylyl
      cyclase in yeast membranes in a RAS2-dependent manner. Northern blot analysis of
      mouse brain poly(A)+ RNA reveals two major transcripts of approximately 1700 and
      5200 nucleotides. Transcripts were found also in mouse heart and at a lower level
      in liver and spleen.

PMID- 1376248
TI  - Empty spiracles, a gap gene containing a homeobox involved in Drosophila head
      development.
AB  - The empty spiracles (ems) gene of Drosophila melanogaster is necessary for proper
      head formation and the development of the posterior spiracles. We have isolated a
      homeobox-containing gene, W13, by cross-homology using the Drosophila muscle
      segment homeobox gene (msh) as a probe. The W13 gene maps at 88A, where the ems
      locus has been previously localized genetically. The sequence alterations found
      in the W13 coding region from two mutant ems alleles show that W13 is the ems
      gene. A 2.4 kb RNA corresponding to the ems transcript is expressed from cellular
      blastoderm throughout all embryonic and larval stages. In situ hybridization to
      whole mount embryos reveals two domains of expression. During the cellular
      blastoderm stage ems is expressed in the developing head in a single anterior
      band. This is correlated with its possible function as an anterior gap gene that
      is expressed in the preantennal, antennal and intercalary segments and is
      required for the development of the antennal sense organ, the optic lobe and
      parts of the head skeleton. The early expression of the ems gene is controlled by
      the anterior morphogen bicoid (bcd). Using a gene fusion we identified a cis
      acting element which is a target for the bcd gene product. Later during
      embryogenesis ems is expressed in lateral regions of each segment, where the
      tracheal pits form and lateral neuroblasts originate, as well as in the posterior
      spiracles. This late expression partially correlates with defects seen in the
      tracheal tree of ems embryos. In addition to a homeodomain, the N-terminal
      portion of the predicted protein sequence is very proline-rich, whereas the C
      terminus has an acidic profile consistent with the role of the ems gene product
      as a transcription factor.

PMID- 1376249
TI  - The Caenorhabditis elegans sex determining gene fem-3 is regulated post
      transcriptionally.
AB  - The fem-3 gene of Caenorhabditis elegans is required for male development. Both
      maternal and zygotic fem-3 activities are required for spermatogenesis in the XX
      hermaphrodite germline and for male development in somatic and germline tissues
      XO (male) animals. Here we show that fem-3 RNA is contributed to embryos as a
      maternal product and that this RNA is degraded early in embryonic development.
      The poly(A) tail of embryonic fem-3 RNA is substantially longer than that of
      adult hermaphrodites which indicates that poly(A) tail lengthening probably
      occurs at or soon after fertilization. During subsequent development, fem-3
      poly(A) tails shorten. The amount of fem-3 RNA in XX and XO embryos is
      equivalent, suggesting sex-specific regulation of maternal fem-3 activity occurs
      post-transcriptionally. The sequence of fem-3 predicts an open reading frame that
      could encode a soluble protein; putative fem-3 null mutants truncate this open
      reading frame. We discuss the implications of these results for the regulation
      and function of fem-3.

PMID- 1376251
TI  - Cytomegalovirus-enhanced induction of chromosome aberrations in human peripheral
      blood lymphocytes treated with potent genotoxic agents.
AB  - Human cytomegalovirus (HCMV) has been shown to increase the frequency of
      chromosome aberrations, primarily chromatid-type, in human peripheral blood
      lymphocytes (PBLs). Because HCMV persists in most humans, pathologically
      activates cells, and may perturb the cell cycle, we investigated the possibility
      that HCMV-infected cells have a modified sensitivity to chromosome damage induced
      by genotoxic chemicals. Uninfected PBLs exposed to bleomycin (3 to 100
      micrograms/ml) demonstrated a linear increase in the frequency of chromosome
      aberrations. HCMV infection of PBLs at an intensity that did not cause detectable
      damage followed by exposure to the same concentrations of bleomycin resulted in a
      significant enhancement (p less than 0.01) in the frequency of chromosome
      aberrations relative to the effect of bleomycin alone. A more than additive
      enhancement of the frequency of chromosome aberrations was also noted in HCMV
      infected PBLs exposed to 4-hydroxyaminoquinoline-1-oxide (4-HAQO; 0.1 to 0.3
      micrograms/ml) relative to uninfected cells treated with 4-HAQO alone. No
      increase in the percentage of aberrant cells or the frequency of chromosome
      aberrations was observed in HCMV-infected cells treated with 4-nitroquinoline-1
      oxide (4-NQO) relative to similarly treated uninfected PBLs. These results
      suggest that HCMV can potentiate the induction of chromosome aberrations in human
      PBLs caused by potent DNA damaging agents.

PMID- 1376250
TI  - Plant and mammalian sorting signals for protein retention in the endoplasmic
      reticulum contain a conserved epitope.
AB  - We studied protein sorting signals which are responsible for the retention of
      reticuloplasmins in the lumen of the plant endoplasmic reticulum (ER). A non
      specific passenger protein, previously shown to be secreted by default, was used
      as a carrier for such signals. Tagging with C-terminal tetrapeptide sequences of
      mammalian (KDEL) and yeast (HDEL) reticuloplasmins led to effective accumulation
      of the protein chimeras in the lumen of the plant ER. Some single amino acid
      substitutions within the tetrapeptide tag (-SDEL, -KDDL, -KDEI and -KDEV) can
      cause a complete loss of its function as a retention signal, demonstrating the
      high specificity of the retention machinery. However, other modifications confer
      efficient (-RDEL) or partial (-KEEL) retention. It is also shown that the
      efficiency of protein retention is not significantly impaired by an increased
      ligand concentration in plants. The efficiently retained chimeras (-KDEL, -HDEL
      and -RDEL) were shown to be recognized by a monoclonal antibody directed against
      the C-terminus of the mammalian reticuloplasmin protein disulfide isomerase
      (PDI). The recognized epitope is also present in several putative
      reticuloplasmins in microsomal fractions of plant and mammalian cells, suggesting
      that the antibodies recognize an important structural determinant of the
      retention signal. In addition, data are discussed which support the view that
      upstream sequences beyond the C-terminal tetrapeptide can influence or may be
      part of the structure of reticuloplasmin retention signals.

PMID- 1376252
TI  - Bed-side infection screening of ICU patients using gram stained smears.
AB  - Bronchial, abdominal or pleural aspirates (n = 364) collected from 165 ICU
      patients were both cultivated and evaluated microscopically using Gram stained
      smears, and the results were compared: 331 aspirates (91%) were classified
      correctly. Fungi were confirmed in all cases (21/21, sensitivity and specificity
      100%). Gram-negative findings (n = 66) had a specificity of 97% (2/66
      reclassified as Gram positive by culture): 21/85 Gram-negative cultures were
      overlooked by the Gram method (sensitivity 75%). Of 106 Gram-positive results,
      culture was negative in 10/106 and 7/106 were diagnosed as Gram-negative
      (specificity 84%). Sensitivity was 98% (only 2/91 not detected by the Gram
      technique). In 171 cases, no organisms were seen; specificity was 92% (Gram
      negative bacteria cultivated in 14/171). Sensitivity was 94% (10/167 misdiagnosed
      as Gram-positive). Gram diagnoses were available 63 +/- 14 h prior to the culture
      test results. Treatment decisions based upon the Gram results were correct in 90%
      (326/364). It is concluded that Gram stained smears are a valuable tool for bed
      side infection screening in ICU patients.

PMID- 1376253
TI  - Standards in monitoring acute experimental pancreatitis.
AB  - Animal models are helpful and irreplaceable tools in studying etiological factors
      and the pathogenesis of acute pancreatitis. For the comparability of the results,
      standards in monitoring of acute experimental pancreatitis are necessary. In this
      article an overview about different models of acute experimental pancreatitis and
      their severity are given. We also describe obligatory and facultative standard
      parameters in monitoring of acute experimental pancreatitis.

PMID- 1376254
TI  - Functional characterization of non-human primate erythrocyte immune adherence
      receptors: implications for the uptake of immune complexes by the cells of the
      mononuclear phagocytic system.
AB  - Erythrocytes from primates express an immune adherence (IA) receptor that binds
      complement-opsonized immune complexes (IC) both in vivo and in vitro. We have
      analyzed the immunochemical and functional properties of the IA receptor from
      erythrocytes from species that have been used for in vivo IC clearance studies
      and have compared these properties to the human IA receptor (which is called
      complement receptor type 1, CR1). Erythrocytes from all species (chimpanzee,
      baboon, rhesus and cynomolgus monkey) bind antibody/double-stranded DNA IC when
      opsonized with autologous complement. However, IC which are bound to chimpanzee
      erythrocytes are not released upon addition of chimpanzee serum (which contains
      factor I activity), while IC bound to baboon erythrocytes and human erythrocytes
      are released upon addition of autologous serum. Anti-human CR1 monoclonal
      antibodies (mAb) E11 and HB8592 bind to erythrocytes from all species examined
      and the number of mAb epitopes per erythrocyte correlated with the number of IC
      that could bind to the erythrocyte under saturating conditions. However, a number
      of interesting differences between the species are observed with other mAb. The
      anti-CR1 mAb 1B4 and 3D9, which block recognition of ligand by CR1, did not bind
      to chimpanzee erythrocytes and bound partially to rhesus and cynomolgus monkey
      erythrocytes. In addition, the ability of autologous serum to induce release of
      erythrocyte-bound IC correlates with the presence of these epitopes. These
      findings, taken in context with previous clearance studies, suggest that serum
      mediated release may not be required for the rapid transfer of the IC from the
      erythrocyte to the mononuclear phagocytic system.

PMID- 1376255
TI  - Non-additive effects of multiple amino acid substitutions on antigen-antibody
      recognition.
AB  - Synthetic peptides have been used to mimic the main antigenic site of foot-and
      mouth disease virus (FMDV) of serotype C and of several variant isolates. This
      region includes multiple continuous B cell epitopes. The effect of single amino
      acid replacements, individually or in combination, on antigen specificity has
      been evaluated using monoclonal antibodies. Quantitative enzyme immunodot assays
      have shown that both additive and non-additive effects of multiple replacements
      occur in continuous B cell epitopes, with regard to antibody recognition.
      Antigenically critical single replacements may be compensated by other, non
      critical replacements. Thus, the role of a single amino acid on antibody
      recognition depends on the sequence context in the antigenic domain. The non
      additive effects of multiple replacements may modulate the extent of antigenic
      diversification of highly variable RNA viruses, and keep viruses confined within
      antigenic groups by precluding linear antigenic divergence.

PMID- 1376257
TI  - Synthetic peptide libraries in the determination of T cell epitopes and peptide
      binding specificity of class I molecules.
AB  - Major histocompatibility complex (MHC) class I molecules combine with short
      peptides of defined length and sequence. Here we describe an approach that may be
      used in the analysis of peptide preference of different allelic MHC class I
      molecules, and in the determination of T cell epitopes. We produced synthetic
      "peptide libraries" of limited complexity by standard peptide chemistry. Using
      these peptide mixtures we show that H-2 Kb molecules can accommodate both 8- and
      9-residue peptides, whereas Db molecules are unable to combine with peptides
      shorter than 9 amino acids present in these libraries. When these peptide
      mixtures are used to provide "fingerprints" of Db molecules and mutants thereof,
      both loss and gain of the ability to combine with certain peptides is observed.
      For the Kbm1 mutant a strong influence of amino acid substitutions in class I
      molecules on the peptides selected is observed. In these synthetic peptide
      mixtures, the presence of a specific T cell epitope, known to be represented
      once, can be detected. This approach may be extended to the identification of new
      T cell epitopes from larger peptide libraries.

PMID- 1376256
TI  - Interleukin-1 induces protein tyrosine phosphorylation in T cells.
AB  - Interleukin (IL)-1 alpha activates multiple signal transmission pathways in the T
      helper type 2 cell line, D10A, and these pathways are linked to two separate IL-1
      receptors (IL-1R). In the present report we show that IL-1 induces the activation
      of tyrosine kinase in these cells, leading to tyrosine phosphorylation of a
      subset of proteins of 38, 75, 97 and 115 kDa. This type of phosphorylation is
      prevented by a monoclonal antibody directed against the 80-kDa IL-1R and by
      tyrphostins which are specific inhibitors of tyrosine kinases. In addition, this
      inhibitor blocks IL-1-and IL-2-induced proliferation in D10A cells as well as the
      c-myc and c-myb proto-oncogene mRNA expression in response to IL-1.
      Interestingly, the inhibitor of cAMP-dependent kinase, H-8, only blocks IL-1
      induced c-myb, but not c-myc mRNA expression. Altogether, our results demonstrate
      that the activation of a tyrosine kinase(s) is an early and major event that
      happens after IL-1/IL-1R interaction, leading to an increase in intracellular
      cAMP which results in c-myb and IL-5 mRNA expression. Independent of cAMP, by
      tyrosine phosphorylation of specific substrates IL-1 also induces c-myc and IL-6
      mRNA expression and cellular proliferation.

PMID- 1376258
TI  - Membrane molecules which trigger the production of interleukin-1 and tumor
      necrosis factor-alpha by lipopolysaccharide-stimulated human monocytes.
AB  - We have investigated the role of the membrane molecules CD11/CD18 and CD14 which
      may mediate the binding of lipopolysaccharide (LPS) to human monocytes, in the
      induction of the production and release of interleukin (IL)-1 and tumor necrosis
      factor-alpha (TNF-alpha) by LPS-stimulated cells. Blockade of CD11a, CD11b and
      CD18 with saturating concentrations of specific mAb did not inhibit the release
      of cytokines from LPS-stimulated monocytes. In contrast, inhibition of the
      release of IL-1 beta and TNF-alpha occurred in monocytes cultures that had been
      pretreated with either of two monoclonal antibodies (mAb) recognizing different
      epitopes on the CD14 molecule. The binding of LPS to CD14 has been previously
      shown to require serum factors. In the present study, we found that serum had an
      enhancing effect on the release of IL-1 and TNF-alpha from LPS-stimulated
      cultures of normal human monocytes. The inhibitory effect of anti-CD14 mAb was,
      however, observed in cultures performed in the presence or in the absence of
      serum, suggesting that triggering of IL-1/TNF-alpha release by CD14 is
      independent of LPS-binding proteins or other serum proteins. IL-1 beta and TNF
      alpha were also released from LPS-stimulated cultures of monocytes from patients
      with paroxysmal nocturnal hemoglobinuria lacking expression of CD14. Thus, CD14
      but not CD11/CD18 can trigger serum-dependent and independent cytokine release
      from endotoxin-stimulated normal human monocytes; CD14 is not, however, the only
      LPS receptor that is involved in the secretory response of endotoxin-stimulated
      cells.

PMID- 1376259
TI  - Both LFA-1-positive and -deficient T cell clones require the CD2/LFA-3
      interaction for specific cytolytic activation.
AB  - We investigated the capacity of T lymphocytes from a leukocyte adhesion-deficient
      (LAD) patient to respond to alloantigen. Leukocytes of this patient completely
      lacked LFA-1 surface expression due to the absence of mRNA coding for the LFA-1
      beta chain. Despite the absence of LFA-1, T lymphocytes obtained from this
      patient, cultured with allogeneic stimulator cells (lymphoblastoid B cells JY),
      were capable of lysing JY cells. Furthermore, two T cell clones (one CD4+ and one
      CD8+), generated from this lymphocyte culture, specifically lysed the allogeneic
      lymphoblastoid JY cells. The cytolytic capacity of LFA-1-negative T lymphocytes
      and T cell clones was comparable to that of control LFA-1-positive T cells with
      allospecificity against JY. Detailed analysis of the CD4 positive and LFA-1
      negative T cell clone demonstrated that it specifically recognized HLA-DQ.
      Antibody inhibition studies showed that the CTL/target cell interaction was
      mediated through the CD2/LFA-3 adhesion pathway. LFA-1 expressed by the target
      cells did not participate in the CTL/target cell conjugate formation and
      contributed only minimally to the cytotoxic activity. Moreover, when allogeneic
      LFA-1-deficient B cells, bearing the appropriate HLA-DQ alloantigen, were used as
      target cells, significant levels of specific cytotoxicity were measured, further
      excluding a role for LFA-1 in this interaction. The adhesion molecules, VLA-4,
      CD44 and L-selectin (LECAM1) were not involved. These results demonstrate that
      LFA-1-negative T lymphocytes can exert allospecific cytotoxicity and that
      CTL/target cell contact is mediated through the CD2/LFA-3 route. This observation
      may explain in part why in LAD patients viral infections, cleared largely by T
      cells, are less frequently observed than bacterial infections, in which
      phagocytic cells play a major role.

PMID- 1376260
TI  - Molecular cloning and expression of the murine RANTES cytokine: structural and
      functional conservation between mouse and man.
AB  - The infiltration and activation of monocytes is a hallmark of chronic
      inflammation, including that associated with a variety of disease states such as
      rheumatoid arthritis, atherosclerosis, and various autoimmune conditions.
      Recently, a family of small molecular mass proteins has been described which
      appear to have inflammatory properties, including chemoattractant effects on
      monocytes. We report here on the molecular cloning, characterization, and
      functional expression of mu RANTES, a new murine member of this family. mu RANTES
      expressed in a mammalian expression system is an approximately 8-kDa protein
      exhibiting immune cross-reactivity with a rabbit polyclonal antiserum generated
      against human RANTES. Boyden chamber chemotaxis experiments reveal some lack of
      species specificity in monocyte chemoattractant potential, as recombinant mu
      RANTES attracts human monocytes in a dose-dependent fashion in vitro. mu RANTES
      and its human homolog share approximately 85% amino acid identity, a higher level
      of conservation than that seen with any other species homologs in this cytokine
      family, and second only to transforming growth factor-beta among reported immune
      cytokines.

PMID- 1376261
TI  - Staphylococcal enterotoxin B as a potent suppressant of T lymphocytes: trace
      levels suppress T lymphocyte proliferative responses.
AB  - Staphylococcal enterotoxins have long been known to be powerful stimulators of T
      lymphocytes in mouse and man. In a previous study we showed that high
      concentrations of staphylococcal enterotoxin serotype B (SEB) failed to stimulate
      strong proliferative responses by Lewis rat T lymphocytes. Moreover,
      concentrations of SEB (10-50 micrograms/ml) that stimulated optimal mouse T
      lymphocyte proliferative responses suppressed a mitogen- or antigen-induced rat T
      lymphocytes proliferative responses. The present study shows that SEB at low
      concentrations (as low as 10(-3)-10(-4) micrograms/ml) and often also trace
      levels (about 10(-6)-10(-7) micrograms/ml) suppresses both rat and mouse T
      lymphocytes proliferative responses to mitogen or antigen. Furthermore, under
      different circumstances, SEB may have conflicting effects on the same T cells.
      While high concentrations (1-50 micrograms/ml) of SEB stimulate certain mouse T
      cell clones, low concentrations or trace levels have a potent suppressive effect
      on the same clones. The results indicate that the in vitro conflicting effects of
      SEB on the same T cells are concentration dependent and may reflect its in vivo
      effects on SEB-reactive T lymphocytes. The suppression of the mitogen- or antigen
      induced stimulation of T cell clones by SEB was direct and did not require the
      agency of suppressor cells. Furthermore, the suppression by low amounts of SEB
      was not major histocompatibility complex restricted and affected a large
      proportion of both rat and mouse T lymphocyte subpopulation, regardless of their
      antigenic specificity. The concomitant suppressogenic and stimulatory
      characteristics of SEB support the conclusion that, under different conditions,
      SEB can be considered a "super-suppressogen" as well as a "super-antigen".
      Overall, the results suggest that SEB, and possibly other bacterial toxins, could
      be useful in immunomodulation of specific T cell responses.

PMID- 1376262
TI  - HLA-DR peptide-induced alloreactive T cell lines reveal an HLA-DR sequence that
      can be both "dominant" and "cryptic": evidence for allele-specific processing.
AB  - Previously, we reported on a T cell line, ThoU6, which we obtained through
      stimulation of DPw3+ cells with a synthetic "DR3 peptide" with a sequence
      identical to the third hypervariable region of the DRB1*0301 chain. This T cell
      line recognizes both the synthetic peptide presented by DPw3 as well as DR3+
      DPw3+ stimulator cells. This implies that the synthetic DR3 peptide has a natural
      counterpart in DR3-positive cells. Here we describe the recognition pattern of
      another T cell line that was sensitized with the same synthetic DR3 peptide. This
      T cell line, BieU6, shows both HLA-DRw13/Dw18 (self)-restricted recognition of
      the synthetic DR3 peptide and allorecognition towards DR13/Dw19, a molecule which
      is highly homologous to Dw18, in the absence of synthetic peptide. These results
      suggest that the epitope formed by the Dw18 molecule plus the synthetic DR3
      peptide and recognized by T cell line BieU6 mimics the Dw19 molecule. The
      potential role for a Dw19-specific peptide is discussed. The inability of T cell
      line BieU6 to recognize Dw18+ DR3+ cells indicates that, in this case, the
      synthetic DR3 peptide is "cryptic", i.e. does not have a natural counterpart that
      is effectively presented to T cells. Mapping of the shortest peptides recognized
      by T cell lines ThoU6 and BieU6 indicate that these sequences are fully
      overlapping. We, therefore, suggest that the antigen-presenting molecules, HLA
      DPw3 and HLA-Dw18, differ in their accessibility for self peptides derived from
      the third hypervariable region of DR molecules. These observations may be
      explained by allele-specific processing.

PMID- 1376263
TI  - T cell responses to human recombinant acetylcholine receptor-alpha subunit in
      myasthenia gravis and controls.
AB  - Antibodies against the nicotinic acetylcholine receptor (AChR) of the
      neuromuscular junction are detectable in most patients with myasthenia gravis
      (MG) and assumed to participate in the destruction of the AChR, thereby, causing
      the characteristics signs and symptoms of the disease. The extent and importance
      of T cell responses to AChR and its subunits in MG are still unsettled. We have
      now examined T cell reactivities using human recombinant AChR-alpha subunit as
      antigen. Upon recognition of appropriate antigen in an MHC-class II-restricted
      fashion, memory T cells secrete interferon-gamma (IFN-gamma). Adopting this
      principle in an immunospot assay we found that 73% of MG patients had recombinant
      human AChR-alpha subunit-reactive T cells at a median value of 1 per 56,000 blood
      mononuclear cells, while only 27% of the MG patients responded to the alpha
      subunit in a conventional lymphocyte proliferation assay. This compares with even
      lower numbers of AChR-reactive T cells and 14% positivity in the proliferation
      assay among control subjects. The T cell responses to the control antigens
      purified protein derivative and myelin basic protein did not differ between MG
      and controls, underlining the specificity of an augmented T cell reactivity to
      AChR-alpha subunit in MG. Alpha Subunit-specific T cell lines and clones
      propagated from patients with MG and healthy controls yielded a high proportion
      of alpha subunit-reactive T cells in the IFN-gamma immunospot assay. Their
      appearance was inhibited by the addition of monoclonal anti-MHC class II
      antibodies, demonstrating that an MHC-restricted T cell response was measured.
      Our data underline that the AChR-alpha subunit is a major T cell autoantigen in
      MG.

PMID- 1376264
TI  - Complement regulatory proteins at the feto-maternal interface during human
      placental development: distribution of CD59 by comparison with membrane cofactor
      protein (CD46) and decay accelerating factor (CD55).
AB  - The complement (C) regulatory proteins decay-accelerating factor (DAF, CD55) and
      membrane cofactor protein (MCP, CD46), which control C3 convertases, together
      with CD59, an inhibitor of the membrane attack complex (MAC), were found to be
      present in the developing human placenta from at least 6 weeks of gestation until
      term. Immunostaining revealed differences in the distribution of these proteins
      on the fetally derived trophoblast epithelium, especially in early placentae
      which contain trophoblast populations of diverse proliferative potential and
      differentiation status. Expression of all three proteins occurred on the
      terminally differentiated syncytiotrophoblast epithelium covering chorionic villi
      and which is in direct contact with maternal blood. CD59 was also expressed on
      the underlying villous cytotrophoblast cells and on their extra-villous
      derivatives. These two populations showed differential expression of the C3
      convertase regulators. Villous cytotrophoblast cells expressed MCP but were
      largely devoid of DAF. Proliferation of this population to generate extra-villous
      cytotrophoblast cell columns was associated with both an increase in DAF
      expression and a decrease in MCP expression. Throughout placental development,
      expression of DAF appeared to be lower than that of MCP and CD59 as assessed by
      solid-phase binding assays on isolated trophoblast membranes. Early placentae
      were also found to contain both DAF+ and DAF- chorionic villi. Conversely,
      expression of CD59 appeared comparatively high and transcripts for CD59 were
      found to be much more abundant than those for DAF in purified trophoblast cells.
      C regulatory proteins appear to play an important role throughout gestation in
      protecting the fetally derived human conceptus from maternal C. The differential
      expression patterns of the proteins on trophoblast may reflect differences in
      requirement for specific functional activities at different locations within the
      placenta.

PMID- 1376265
TI  - Thymic hyperplasia in transgenic mice caused by immortal epithelial cells
      expressing c-kit ligand.
AB  - To dissect mechanisms that co-ordinate specific events in thymopoiesis we have
      characterized alterations in thymic structure and function caused by expression
      of a transgene. This gene encodes SV40Tag and is specifically expressed in a
      subset of thymic epithelial (TE) cells around birth. As a result the number of
      immortal TE cells increases, thymic mass increases (up to 3 g), and thymopoiesis
      is expanded. The latter is reflected by a approximately 100-fold increase of the
      major thymocyte subsets and increased peripheral T cell counts. Grossly
      hyperplastic thymi retain many but not all morphological features of a normal
      thymus. Also in grafts, SV40Tag+ TE cells steer expansion (up to 8 g) and
      organize a tissue with mainly cortex-like features that includes mainly SV40Tag+
      TE cells, thymocytes, and macrophages. To investigate expression of specialized
      gene functions in the immortal TE cells, a cell line was derived. The Epi-A1 cell
      line expresses the genes for major histocompatibility complex class I and II, Thy
      1, interleukin (IL)-6, IL-7, macrophage-colony-stimulating factor, and
      transforming growth factor-beta 3. Most importantly, Epi-A1 cells also express
      the IL-4 receptor and the c-kit ligand (KL), a factor that, in concert with
      commitment factors, channels progenitors into hemopoietic lineages. The
      expression of low constitutive levels of KL mRNA does not require IL-4, but KL
      mRNA levels are increased dramatically in response to IL-4. Since constitutive
      expression of KL mRNA in vivo is restricted to a small subset of TE cells in the
      thymus, our findings reveal a novel specific interaction between thymocytes and a
      specialized subset of TE cells.

PMID- 1376267
TI  - Preferred size of peptides that bind to H-2 Kb is sequence dependent.
AB  - The identification of naturally processed viral peptides reveals that major
      histocompatibility complex (MHC) class I epitopes are composed of nine or eight
      amino acid residues. Peptides eluted from H-2 Kb MHC class I molecules have been
      suggested, as a class, to be eight amino acid residues long. To assay for peptide
      class I interactions, a stabilization assay described for surface labeled "empty"
      class I molecules was employed, but on biosynthetically labeled class I
      molecules. The Sendai virus nucleoprotein-derived octapeptide APGNYPAL does not
      bind and stabilize Kb molecules, whereas other octameric Kb-restricted peptides
      and the nonameric peptide FAPGNYPAL interact stably. We attribute the failure of
      Sendai octamer binding to the presence of proline in position two: replacement of
      proline renders the resulting octamers as efficient as FAPGNYPAL for binding and
      stabilization of H-2 Kb. Substitution of glycine in position three of APGNYPAL
      slightly improves its Kb stabilizing capacity. Iodination of the tyrosine residue
      significantly alters the binding properties of the nonamer peptide. We conclude
      that the length of epitopes as selected by the class I Kb molecule is influenced
      by their sequence and suggest that proper positioning of the NH2 terminus of
      peptides is essential for class I stabilizing properties. The ability to
      stabilize newly synthesized "empty" class I molecules with peptide argues against
      an involvement of beta 2 microglobulin exchange in the experiments described
      here.

PMID- 1376266
TI  - Specific epitope-induced conversion of CD8+ memory cells into effector cytotoxic
      T lymphocytes in vitro: presentation of peptide antigen by CD8+ T cells.
AB  - The requirements for the conversion of CD8+ memory T cells into effector class I
      major histocompatibility complex (MHC) Kd-restricted cytotoxic T (Tc) cells in
      vitro have been studied. Purified CD8+ splenocytes from influenza A/WSN-primed
      BALB/c (H-2d) mice stimulated with a synthetic nucleoprotein peptide 147-158 R156
      (NPP) alone generated Tc cells specific for influenza virus-infected target
      cells. No additional requirements for accessory cells or their lymphokine
      products were necessary indicating that peptide antigen (Ag) in association with
      Kd was presented on CD8+ T cells. The evidence for presentation of NPP by CD8+ T
      cells was supported by the use of CD8+ memory T cells from semiallogeneic bone
      marrow radiation chimeras of P1----F1 type (H-2b----[H-2d x H-2b]F1). Memory CD8+
      splenocytes from A/WSN-immune chimeras did not develop into secondary effector Tc
      cells as a result of a 4-day culture with NPP alone, however, were able to do so
      if NPP was presented by Kd-bearing Ag-presenting cells. In addition, these
      results exclude the possibility of direct recognition of free NPP molecules by
      the specific T cell receptor of CD8+ memory T cells. CD8+ memory splenocytes (H
      2b) from chimeras were also able to develop into functionally active Tc cells as
      a result of presentation of Db-restricted synthetic peptide (NP 366-374) with a
      sequence derived from influenza virus nucleoprotein with high affinity for Db MHC
      class I molecules. Blockade of endogenously produced interleukin 2 (IL-2)
      activity by anti-IL-2 or anti-IL-2 receptor monoclonal antibody in the culture of
      CD8+ memory T cells during a 4-day NPP stimulation completely abolished Tc cell
      generation, indicating that the utilization of this lymphokine is absolutely
      required for the secondary Tc cell development. These findings demonstrate that
      CD8+ memory T cells per se are able to recognize the restimulating epitope as a
      result of its presentation by CD8+ T cells and develop into cytolytically active
      and highly specific Tc cells with no requirements for other cellular helper
      components or their lymphokine products.

PMID- 1376269
TI  - Lipopolysaccharide induces up-regulation of CD14 molecule on monocytes in human
      whole blood.
AB  - We examined by flow cytometry the expression of lipopolysaccharide (LPS) receptor
      CD14 molecule on monocytes after addition of LPS to human whole blood. Within 30
      min LPS induced an increase in monocyte CD14 expression, peaking between 1 and 3
      h and followed by a slow decrease. Maximal increase in anti-CD14 monoclonal
      antibody binding sites was estimated as twofold the basal value. This effect,
      already observed with very low concentrations of LPS (10 pg/ml), was dose
      dependent. Protein synthesis was not involved in the CD14 hyperexpression since
      it was not influenced by co-incubation with cycloheximide. Finally, LPS-induced
      up-regulation of monocyte CD14 was associated with an increased binding of
      fluoresceinated LPS. We conclude that LPS in whole blood up-regulates the
      expression of its own CD14 receptor on monocytes, a phenomenon that could be
      relevant to the pathogenesis of gram-negative sepsis.

PMID- 1376268
TI  - Fc gamma RIII activation is different in CD16+ cytotoxic T lymphocytes and
      natural killer cells.
AB  - The transmembrane protein CD16 (Fc gamma RIII) is detected on activated
      macrophages, natural killer (NK) cells and a small subset of T lymphocytes. From
      CD3-CD56+ CD16+bright NK cells and CD3+ CD56+ CD16+dim non-major
      histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) clones
      were generated reflecting the stable, but different, CD16 expression of the
      respective peripheral blood subpopulations. To compare the role of CD16 on NK
      cells and non-MHC-restricted CTL, Fc gamma RIII activation and its mechanisms
      were investigated using monoclonal antibodies (mAb). Cross-linking of CD16
      induced Ca2+ influx in CD16+bright NK clones. In contrast, there was no Ca2+
      mobilization after CD16 activation in CD16+dim CTL, which revealed a good
      response to cross-linking of CD3 antigen. Pretreatment with CD16 mAb alone or
      cross-linked CD16 mAb did not block the CD3 response of CD16+dim CTL. Again, CD16
      cross-linking induced more interferon-gamma transcription in NK cell clones than
      in non-MHC-restricted CTL clones. Also a higher tumor necrosis factor-alpha
      production of NK clones after CD16 cross-linking compared to CD16+dim CTL could
      be observed. These data suggest that after CD16 activation CD16+dim CTL and
      CD16+bright NK cells use different second messengers. In addition, signal
      transduction via CD3 and CD16 appears to function independently in CD16+dim non
      MHC-restricted CTL.

PMID- 1376270
TI  - Role of nitric oxide in adrenal medullary vasodilation during catecholamine
      secretion.

PMID- 1376271
TI  - Effect of endothelium on the actions of sympathetic and sensory nerves in the
      perfused rat mesentery.
AB  - We and others have previously demonstrated that pretreatment with capsaicin
      produces an augmentation of vasoconstrictor responses to transmural nerve
      stimulation. In the present study, removal of endothelium by saponin or
      inhibition of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester
      produced an augmentation of vasoconstrictor responses to transmural nerve
      stimulation, responses which were further potentiated after treatment with
      capsaicin to desensitize sensory nerves. Capsaicin treatment decreased
      vasodilator responses to acetylcholine, but only at low acetylcholine
      concentrations. Potentiation by capsaicin of vasoconstrictor responses to
      transmural nerve stimulation was not affected by indomethacin. In the presence of
      guanethidine and methoxamine, transmural nerve stimulation caused vasodilator
      responses in the perfused rat mesentery. These responses were unaffected by
      removal of endothelium, as were vasodilator responses to exogenous calcitonin
      gene-related peptide (CGRP). In contrast, substance P did not produce any
      relaxation in the methoxamine-contracted mesentery. This study suggests that
      facilitation of vasoconstrictor responses to transmural nerve stimulation after
      capsaicin treatment primarily reflects inhibition of sensory nerve effects
      resulting in an increase of sympathetic vasoconstrictor actions. The present
      results also suggest that vasodilator responses to sensory nerve activation or
      exogenous CGRP are endothelium-independent and that substance P does not
      significantly contribute to modulation of vascular tone in the rat mesentery.

PMID- 1376273
TI  - Veratridine evokes release of calcitonin gene-related peptide from capsaicin
      sensitive nerves of rat urinary bladder.
AB  - The effect of superfusion with veratridine on the release of calcitonin gene
      related peptide-like immunoreactivity (CGRP-LI) was studied in slices of rat
      urinary bladder. Exposure to veratridine (1-200 microM) produced a concentration
      related release of CGRP-LI. Veratridine (50 microM)-evoked CGRP-LI release was
      abolished in slices pre-exposed to capsaicin (10 microM for 40 min) or superfused
      in a Ca(2+)-free medium containing 1 mM EDTA. After exposure to veratridine (50
      microM for 40 min), capsaicin (10 microM) was still able to release CGRP-LI. CGRP
      LI release evoked by veratridine (50 microM) was inhibited by about 60% by
      tetrodotoxin (0.3 microM), attenuated (30%) by nifedipine (1 microM), and not
      affected by omega-conotoxin (0.1 microM). The capsaicin antagonist ruthenium red
      (10 microM) did not affect veratridine (50 microM)-evoked CGRP-LI release. The
      present results indicate that depolarization by veratridine induces CGRP-LI
      release from capsaicin-sensitive nerve fibres, an effect that is entirely
      dependent on extracellular Ca2+. The Ca2+ influx that promotes CGRP-LI release is
      mediated mostly by nifedipine-, omega-conotoxin- and ruthenium red-insensitive
      channels.

PMID- 1376274
TI  - Nitric oxide participation in renal hemodynamic effect of angiotensin converting
      enzyme inhibitor lisinopril.
AB  - Nitric oxide (NO) contribution to the renal hemodynamic effect of lisinopril was
      assessed in anesthetized rabbits. NG-Nitro-L-arginine (NArg), slightly decreased
      renal blood flow following vehicle. Also, NArg reversed partially the increase in
      renal blood flow caused by DuP 753, and almost completely reversed the effect of
      lisinopril. The results suggest that NO plays an important role in the renal
      hemodynamic effect of lisinopril, more so than its contribution to the effect of
      DuP 753.

PMID- 1376272
TI  - The novel high-affinity antagonist, galantide, blocks the galanin-mediated
      inhibition of glucose-induced insulin secretion.
AB  - This study describes the synthesis and effects of the first antagonist to the
      widely distributed neuropeptide, galanin, which inhibits the secretion of
      insulin. The first galanin antagonist is a 20-amino acid-long chimeric peptide of
      the composition galanin-(1-12)-Pro-substance P-(5-11) amide: Gly-Trp-Thr-Leu-Asn
      Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-Gln-Gln-Phe-Phe-Gly- Leu-Met amide. The peptide
      dose dependently (IC50 = 1.0 nM) antagonizes the galanin-mediated inhibition of
      the glucose-induced insulin secretion from mouse pancreatic islets. The
      antagonist was also found to displace 125I-monoiodo-[Tyr26]galanin from membranes
      of the insulin producing Rin m 5F cells with an IC50 value of less than 0.1 nM.
      The antagonist is named galantide.

PMID- 1376275
TI  - Increase of nitric oxide production by L-arginine potentiates i.c.v. administered
      beta-endorphin-induced antinociception in the mouse.
AB  - Pretreatment (i.c.v.) of mice with L-arginine but not D-arginine potentiated beta
      endorphin-induced (i.c.v. administered) inhibition of the tail-flick response.
      The potentiation was attenuated by N omega-nitro-L-arginine methyl ester, a
      selective inhibitor of nitric oxide synthase. This observation suggests that
      increased production of nitric oxide from L-arginine mediates the potentiation of
      beta-endorphin-induced antinociception.

PMID- 1376276
TI  - Monoclonal antibody 473 selectively stains a population of GABAergic neurons
      containing the calcium-binding protein parvalbumin in the rat cerebral cortex.
AB  - Monoclonal antibody (MAb) 473 is shown to outline selectively a subpopulation of
      GABAergic neurons containing a specific calcium-binding protein parvalbumin (PV)
      in the adult rat parietal cortex, using preembedding immunocytochemistry at the
      light microscopic level. About 90% of MAb 473 stained cells in the rat parietal
      cortex were PV immunoreactive. Thus we compared MAb 473 staining with that of
      three chemical probes, previously shown to stain selectively a subpopulation of
      PV-containing GABAergic neurons in this brain region, namely, a lectin, Vicia
      villosa agglutinin (VVA), with a specific affinity for terminal N-acetyl
      galactosamine, MAb 3B3 which is specific for chondroitin sulfate proteoglycan and
      MAb HNK-1 which is specific for some types of carbohydrate epitope containing a
      sulfated derivative of glucuronic acid. About 85% of MAb 473 immunoreactive cells
      were shown to be stained with VVA. Furthermore about 90% of MAb 473
      immunoreactive cells were also stained with MAb 3B3. Thus MAb 473 positive cells
      were almost included into VVA and/or MAb 3B3 positive cells. On the other hand
      only about 34% of MAb 473 positive cells were HNK-1 positive, whereas about 44%
      of HNK-1 positive cells were MAb 473 positive. Thus these two MAbs defined
      different, though partially overlapping, subsets of PV-containing GABAergic
      neurons in the rat parietal cortex.

PMID- 1376277
TI  - Evidence for excitatory amino acid neurotransmitters in the geniculo-cortical
      pathway and local projections within rat primary visual cortex.
AB  - To examine the organization of axon collaterals of neurons that selectively take
      up and transport excitatory amino acids, we have used retrograde tracing with D
      [3H]Aspartate after injections into different layers of rat primary visual
      cortex. The results show cells in the lateral geniculate nucleus retrogradely
      labeled from the cortex. Additional topographically precise input to the thalamic
      recipient layer 4 originates from neurons in the visual cortex lying in layers
      2/3, 5 and 6. These inputs are reciprocated by point-to-point projections from
      layer 4. Layer 2/3 cells project to layers 5 and 6 in columnar fashion. Putative
      excitatory input to layer 2/3 originates from a vertical column of cells in layer
      5 and the middle of layer 6. In addition layer 2/3 receives input via horizontal
      collaterals of topographically distant upper layer neurons, from more widespread
      projections in lower layer 6, and from very widespread projections of cells at
      the layer 5/6 border. Cells in the depth of layer 5 also distribute collaterals
      within layers 5 and 6. Our findings provide anatomical evidence that the geniculo
      cortical pathway in the mammalian visual system may use excitatory amino acid
      transmitters. In addition, the results support the notion that most long range
      connections that link distant points of the topographic map are excitatory.

PMID- 1376279
TI  - The bilateral bulbar projections of the primary olfactory neurons in the frog.
AB  - Whether or not the frog olfactory neuroreceptor cells project bilaterally to the
      olfactory bulb is still a debated question. We therefore decided to ascertain
      whether bilateral projections of the primary olfactory input exist and if so to
      investigate their extent. Reproducible extracellular bilateral bulbar potentials
      were recorded in the frog following electrical stimulation of dorsal or ventral
      olfactory nerve bundles. The general features of the contralateral evoked
      responses were very similar to those of the ipsilateral response. The
      contralateral response disappeared after transection of the rostral part of the
      olfactory interbulbar adhesion but not following transection of the habenular or
      anterior commissures. Horseradish peroxidase labelling showed that the fiber
      terminations of the olfactory nerve bundle was not restricted to the ipsilateral
      olfactory bulb but included the medial aspects of the contralateral bulb. The
      intertelencephalic sections increased the magnitude of the ipsilateral evoked
      responses. Olfactory bulb isopotential maps revealed a rough topographical
      correspondence between the olfactory neuroepithelium and bulb along the medio
      lateral axis as well as along the dorso-ventral axis. In addition, a projection
      of the medial and central part of the olfactory sac to the medial part of the
      contralateral olfactory bulb through the interbulbar adhesion was confirmed.
      These findings suggest first, that the fibers from the neuro-receptors located in
      either the ventral or the dorsal olfactory mucosae project to both olfactory
      bulbs, and second, that the left and right bulbs exert a constant inhibition on
      each other via the habenular commissure.

PMID- 1376278
TI  - Substance P-, vasoactive intestinal polypeptide-, and cholecystokinin-like
      immunoreactive fiber projections from the superior colliculus to the dorsal
      lateral geniculate nucleus in the rat.
AB  - Substance P (SP)-, vasoactive intestinal polypeptide (VIP)-, and cholecystokinin
      (CCK)-like immunoreactive (LI) neurons were found in the superior colliculus (SC)
      of the rat, and examined to ascertain whether they sent projection fibers to the
      dorsal lateral geniculate nucleus (LGNd). Immunocytochemical staining with
      antisera against SP, VIP, and CCK showed that many immunoreactive neuronal cell
      bodies were located in the superficial layers of the SC, especially in the
      stratum griseum superficiale. The pattern of distribution of these immunoreactive
      neuronal cell bodies in the SC was similar to that of neuronal cell bodies which
      were retrogradely labeled with WGA-HRP (wheat germ agglutinin-horseradish
      peroxidase conjugate) injected ipsilaterally into the LGNd. On the other hand, SP
      , VIP- and CCK-LI axons were seen most densely in the lateral part of the LGNd,
      especially in the small-celled LGNd zone adjacent to the optic tract, where
      anterograde labeling was also observed after injection of WGA-HRP ipsilaterally
      into the superficial layers of the SC. When a lesion was produced by kainic acid
      injection into the superficial layers of the SC, axons showing SP-, VIP-, or CCK
      LI in the LGNd ipsilateral to the lesion were markedly depleted. The results
      indicate that SC-LGNd projection neurons contain SP, VIP, and/or CCK in the rat.

PMID- 1376280
TI  - Rapid effects of insulin on cyclic GMP location in an intact protozoan.
AB  - We studied rapid changes in location of cyclic GMP in Tetrahymena pyriformis.
      Insulin caused cGMP localization in cilia and near the plasma membrane (0.5-1
      min). Later (1-5 min) cGMP localization was diffuse in cytoplasm with perinuclear
      accentuation. Inactive insulin analogs did not elicit these changes.

PMID- 1376281
TI  - Increased assembly of cytoskeletal proteins associated with the transformation of
      human liver cells into fibroblast-like cells.
AB  - A topoisomerase II inhibitor, novobiocin, and a deacetylase inhibitor, butyrate,
      synergistically transformed human liver cells into fibroblast-like cells. This
      morphological change was associated with an increased production of procollagen
      type III peptide and a simultaneous assembly of actin, tubulin, vimentin and
      cytokeratin. Novobiocin and butyrate had no marked effect on the phosphorylation
      state of cytokeratin proteins, but synergistically enhanced [3H]acetate uptake.
      From these results, it can be speculated that protein acetylation plays an
      important role in inducing the assembly of cytoskeletal proteins and the
      morphological transformation of human liver cells.

PMID- 1376282
TI  - Mechanical agitation of very dilute antiserum against IgE has no effect on
      basophil staining properties.
AB  - A previously reported effect of mechanically agitated dilutions of antiserum
      raised against IgE was investigated using the loss of metachromatic staining
      properties of human basophil leukocytes as a model. A series of 24 blind
      experiments was performed in which we determined the number of toluidine blue
      stainable basophils after incubating with vortexed or non-vortexed dilutions of
      anti-IgE. Tenfold serial dilutions were used, in the range 10(21) to 10(30) (6.6
      x 10(-26) to 6.6 x 10(-35) M anti-IgE). We found no evidence for a different
      effect of strongly agitated dilutions, compared to dilutions made with minimal
      physical agitation. In fact, in our hands no effect of extreme dilutions was
      shown at all. We conclude that the effect of extreme dilutions of anti-IgE,
      reported by Davenas et al., needs further clarification and that in this process
      the reproducibility of results between experimenters should be carefully
      determined.

PMID- 1376283
TI  - Nucleotide sequence of a cDNA clone encoding a major allergenic protein in rice
      seeds. Homology of the deduced amino acid sequence with members of alpha
      amylase/trypsin inhibitor family.
AB  - A cDNA clone of rice major allergenic protein (RAP) was isolated from a cDNA
      library of maturing rice seeds. The cDNA had an open reading frame (486
      nucleotides) which coded a 162 amino acid residue polypeptide comprising a 27
      residue signal peptide and a 135-residue mature protein of M(r) 14,764. The
      deduced amino acid sequence of RAP showed a considerable similarity to barley
      trypsin inhibitor [1983, J. Biol. Chem. 258, 7998-8003] and wheat alpha-amylase
      inhibitor [1981, Phytochemistry 20, 1781-1784].

PMID- 1376284
TI  - Cyclic variation of major histocompatibility complex class II antigen expression
      in the human fallopian tube epithelium.
AB  - OBJECTIVE: To systematically investigate the expression of major
      histocompatibility complex (MHC) class II antigens (human leukocyte antigens, HLA
      DR, -DP, and -DQ) on columnar epithelium in the fallopian tube during the
      menstrual cycle. STUDY DESIGN: Biopsies were collected from the fallopian tube
      during laparotomy sterilization and immunoperoxidase staining was performed.
      SETTINGS: Departments of Gynecology and Obstetrics and Clinical Immunology and
      Transfusion Medicine, Uppsala University, Uppsala, Sweden. PATIENTS: Twenty
      healthy fertile women undergoing sterilization at different times of the
      menstrual cycle. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The staining of the
      columnar epithelium was judged on a 4-graded scale according to the distribution
      of class II antigens. RESULTS: A widespread preovulatory HLA-DR expression was
      observed almost completely lining the columnar epithelial cells including the
      luminal surface, whereas postovulatory the HLA-DR expression was withdrawn from
      the surface. The HLA-DP and -DQ antigens varied in a similar way, although not as
      pronounced. CONCLUSIONS: The MHC class II antigen variation in the fallopian tube
      epithelium seen in this study may indicate a hormonal regulation that could
      reflect variable need for local immunocompetence during the menstrual cycle: a
      preovulatory need for immunoreactivity against invading microbes and
      postovulatory an optimal survival of the foreign preimplantation embryo.

PMID- 1376285
TI  - Insulin-like growth factor I receptors in human corpora lutea.
AB  - OBJECTIVE: To determine the presence and binding characteristics of insulin-like
      growth factor (IGF) receptors in corpora lutea (CL) of spontaneous and clomiphene
      citrate (CC)-induced cycles and to identify any relationship between IGF
      receptors and cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17 alpha
      OHP) levels. DESIGN: Women undergoing bilateral tubal ligation were divided into
      two groups. One group received no medication (controls) and the other took 50 mg
      of CC. Midluteal phase CL were recovered at tubal ligation for hormone and
      receptor analysis. SETTING: Patients were recruited from a university hospital
      setting. PATIENTS: Eleven fertile women 26 to 37 years of age requesting
      bilateral tubal ligation were studied. INTERVENTIONS: Four women were given 50
      mg/d of CC from days 5 through 9 of study cycle. Seven women did not take any
      medication. Minilaparotomy bilateral tubal ligation and luteectomy were performed
      7 to 9 days after midcycle urinary (LH) surge. MAIN OUTCOME MEASURES: Insulin
      like growth factor receptor concentrations and binding characteristics and
      cytosol P and 17 alpha-OHP levels in individual CL. RESULTS: Optimal binding for
      125I-IGF-I with membrane fractions of homogenized CL was obtained with incubation
      at 4 degrees C for 16 hours. Specific binding (mean +/- SEM) was significantly
      higher in CC-treated (53.6% +/- 4.8%) than in control cycles (25.9% +/- 5.5%, P
      less than 0.001). Receptor concentrations were also significantly higher in CL
      from CC-induced (145.6 +/- 21.8 pmol/mg protein) than from control cycles (74.8
      +/- 15.2 pmol/mg protein, P less than 0.02). Insulin-like growth factor receptor
      levels correlated with neither serum nor cytosol P and 17 alpha-OHP in CL from
      either cycles. CONCLUSION: Specific IGF-I receptors are present in human CL of
      the menstrual cycle with higher concentrations present in CC-induced cycles. Thus
      IGF may express its action on luteal function through its receptors in CL.

PMID- 1376286
TI  - Testicular mast cell heterogeneity in idiopathic male infertility.
AB  - OBJECTIVE: To determine if the mast cell subclass changes in diseased testes.
      DESIGN: Retrospective. SETTING: University hospital urology clinic and anatomy
      laboratory. PATIENTS, PARTICIPANTS: Fourteen normal men and 50 patients with
      idiopathic male infertility. INTERVENTIONS: Histochemical techniques to identify
      proteoglycans of mast cells were applied to the obtained testicular biopsy
      specimens. MAIN OUTCOME MEASURES: The numbers of the heparin containing mast cell
      and the chondroitin sulfate containing mast cell were measured with light
      microscopy. RESULTS: The total number of mast cells and the ratio of chondoroitin
      sulfate containing mast cells were significantly increased in the testes from
      patients with idiopathic male infertility. CONCLUSION: These results suggest that
      mast cells may play a certain role in the etiology of idiopathic male
      infertility.

PMID- 1376287
TI  - The Steel factor.
AB  - Steel factor (SLF) is a recently identified growth factor which is the gene
      product of the murine Steel locus and a ligand for the c-kit tyrosine kinase
      receptor, the product of the dominant white spotting locus (W). Defects at these
      genetic loci result in aberrant melanocyte, germ cell, and hematopoietic
      development. Both the receptor (c-kit) and the ligand (SLF) have been shown to
      undergo tissue-specific mRNA splicing to produce distinct isoforms which have
      unique biological functions. As predicted by the phenotype of these mutations,
      SLF influences the growth and differentiation of melanocytes, primordial germ
      cells, and a broad spectrum of cell types in the hematopoietic progenitor and
      stem cell hierarchy. SLF has also been shown to have effects on hematopoietic
      lineages not predicted by defects seen in the Steel mouse.

PMID- 1376288
TI  - A chondroitin sulfate proteoglycan that is developmentally regulated in the
      cerebellar mossy fiber system.
AB  - It is known that the mammalian brain contains many kinds of proteoglycans, but
      almost all of them remain to be characterized. In this study, we prepared a
      monoclonal antibody against a phosphate-buffered saline-soluble brain
      proteoglycan (MAb 6B4). MAb 6B4 recognized a 600- to 1000-kDa chondroitin sulfate
      proteoglycan with a 250-kDa core protein (6B4 proteoglycan). The core protein of
      6B4 proteoglycan carried the HNK-1 epitope. Immunohistochemical analysis of the
      adult rat brain indicated that this proteoglycan was expressed on the cell
      surfaces of a subset of neurons. In the hindbrain, 6B4 proteoglycan was highly
      expressed on the cerebellar Purkinje cells and Golgi cells, and at particular
      nuclei including the pontine nuclei and lateral reticular nucleus. Almost all of
      these nuclei were connected to the cerebellum through the mossy fiber system. A
      developmental study indicated that the expression of this proteoglycan changed
      dramatically during the formation of the cerebellar mossy fiber system. The mossy
      fibers from the pontine nuclei expressed 6B4 proteoglycan transiently from
      Embryonic Day 20 (E20) to Postnatal Day 30 (P30), during which time the axonal
      outgrowth and glomerular synapse formation occurred. The Purkinje cells,
      glomeruli, and Golgi cells began to be stained with MAb 6B4 from P10, P16, and
      P20, respectively. These expression stages correspond with the onset of their
      synapse formation. These results suggest that 6B4 proteoglycan is closely
      involved in the development of the cerebellar mossy fiber system.

PMID- 1376289
TI  - Insulin-like growth factor I and II and insulin-like growth factor binding
      protein-2 RNAs are expressed in adjacent tissues within rat embryonic and fetal
      limbs.
AB  - Since the rapid proliferation of cells in a directed manner is a necessary
      component of limb formation, the distribution of locally produced mitogenic
      molecules within the developing limb is of considerable interest. We have used in
      situ hybridization to localize transcripts for both insulin-like growth factor
      binding protein-2 (IGFBP-2) and its ligands, the insulin-like growth factors I
      and II (IGF-I and IGF-II), within limb buds of rat embryos 10-16 days after
      conception (equivalent to stages 1-12 of mouse limb morphogenesis, Wanek et al,
      1989. J. Exp. Zool. 249, 41-49). The mRNA for IGFBP-2 is very abundant in an
      anterior-posterior strip of ectoderm along the distal edge of the limb bud (the
      progenitor of the apical ectodermal ridge or AER) from as early as limb stage 1
      (Embryonic Day 10) and is much less abundant in the rest of the limb ectoderm. A
      high level of IGFBP-2 expression continues to characterize the AER following its
      definitive appearance (stage 3) and throughout its existence (until stage 7).
      This is a period of rapid outgrowth during which the rate of mesodermal cell
      division is highest in cells nearest to the AER. The AER is known to have
      mitogenic activity in vitro and to direct limb outgrowth in vivo, but, until
      recently, few putative molecular correlates of these activities have been
      detected. The transcripts for IGF-I and IGF-II are also present at high abundance
      in developing limbs, especially in mesodermally derived cells. IGF-I mRNA is
      abundant in presumptive limb mesoderm from the beginning of limb outgrowth (just
      before stage 1), but is very low or undetectable in much of the rest of the
      embryo, while IGF-II mRNA becomes very abundant in limb mesoderm at stage 2. The
      distribution in limbs of both IGF-I and IGF-II mRNA changes dramatically during
      outgrowth and differentiation, so that their expression characterizes
      complementary populations of cells by stage 11. Taken together, these data
      suggest that IGFs and the IGF binding proteins, which may modulate IGF action,
      contribute to limb outgrowth and patterning.

PMID- 1376290
TI  - Enzymic activity of salivary amylase when bound to the surface of oral
      streptococci.
AB  - The enzymatic activity of salivary amylase bound to the surface of several
      species of oral streptococci was determined by the production of acid from starch
      and by the degradation of maltotetraose to glucose in a coupled,
      spectrophotometric assay. Most strains able to bind amylase exhibited functional
      enzyme on their surface and produced acid from the products of amylolytic
      degradation. These strains were unable to utilise starch in the absence of
      salivary amylase. Two strains failed to produce acid from starch, despite the
      presence of functional salivary amylase, because they could not utilise maltose.
      Strains that could not bind salivary amylase failed to produce acid from starch.
      In no case was all the bound salivary amylase active, and two strains of
      Streptococcus mitis which bound amylase did not exhibit any enzyme activity on
      their cell surface. The ability to bind amylase may confer a survival advantage
      on oral bacteria which inhabit hosts that consume diets containing starch.

PMID- 1376291
TI  - Organic anxiety disorder with symptoms of akathisia in a patient treated with the
      immunosuppressant FK506.

PMID- 1376293
TI  - Novel vectors for expression of cDNA encoding epitope-tagged proteins in
      mammalian cells.
AB  - Two composite constructs, pNHA and pCHA, are described. These plasmids are
      designed for the expression of cDNA in mammalian cells to produce proteins which
      are tagged with the hemagglutinin epitope sequence, YPYDVPDYA (HA1). The
      insertion of cDNA into the multiple cloning sites of these vectors has the
      advantage of 'tagging' the produced protein at either the N terminus or C
      terminus. To demonstrate the utility of these vectors, pNHA, containing a full
      length cDNA (pNHRP33), was expressed in HeLa cells to produce a HA1-tagged
      peptide. The resulting peptide was purified from the whole-cell extracts by
      immunoprecipitation with an antibody to the tag (mAb12CA5). The mRNA was
      transcribed from a T7 promoter of the pNHRP33 construct, translated in a rabbit
      reticulocyte assay, and the protein product was purified using mAb12CA5 for the
      HA1 epitope. Among other possibilities, these vectors can be used to: (1) study
      protein-protein interactions in a mammalian transcription unit, (2) co-purify
      associated transcription factors, and (3) purify produced proteins when
      antibodies are not available.

PMID- 1376292
TI  - The murine gene encoding the highly conserved Sm B protein contains a
      nonfunctional alternative 3' splice site.
AB  - The cDNA and partial genomic nucleotide (nt) sequences were derived for the mouse
      Sm B polypeptide and compared to the cDNA and genomic sequences encoding human Sm
      B. The deduced amino acid (aa) sequences from the mouse and human genes are
      identical with the exception of a single conserved aa substitution, accounting
      for the ability of anti-Sm antibodies to recognize the Sm polypeptides from a
      broad range of species. The genomic sequence of mouse B gene is similar to the
      human B genomic locus that extends from exon 6 to exon 7. These loci include
      conservation of both 3' alternative splice sites and putative branch points
      required to process B and B' mRNAs in human cells. However, the nt sequence
      downstream from the putative distal 3' splice junction and single nt flanking the
      3' splice site consensus sequence, differ between mouse and human B. This results
      in a murine mRNA with a different predicted secondary structure around the distal
      3' splice site when compared to humans. Thus, secondary structural constraints in
      the mRNA or changes in the exon sequence might prevent recognition of this
      alternative splice site to form B' mRNA in murine tissues.

PMID- 1376295
TI  - [Hepatitis C virus endangers the transplanted liver].

PMID- 1376294
TI  - Ovarian germ cell malignancies: the Yale University experience.

PMID- 1376296
TI  - [Sympathetic reflex dystrophy. Effectiveness of physical therapy treatment of
      Sudeck's syndrome].
AB  - To investigate the impairment of patients with reflex sympathetic dystrophy
      syndrome (RSDS) and to establish the effectiveness of two physiotherapeutic
      regimens in the treatment of this entity, 54 RSDS patients were examined
      clinically, radiologically and scintigraphically an average of 112 days after the
      triggering event. The patients were assigned to either of two treatment groups in
      accordance with the results of preliminary scintigraphic examinations. After
      physiotherapy comprising exercises and cryotherapy either with or without
      galvanic stimulation, a significant therapeutic effect on clinical and
      scintigraphic parameters was found in both treatment groups. Scanning, in
      combination with clinical diagnostic measures proved a valuable tool in the
      diagnostic evaluation, selection of treatment and follow-up in patients with
      RSDS.

PMID- 1376297
TI  - Deletion delta F508 and haplotype analysis of CFTR gene region in Slovak CF
      patients.
AB  - Analysis of a sample of 50 unrelated cystic fibrosis (CF) patients and 46 nuclear
      families from Slovakia (Czechoslovakia) by the polymerase chain reaction and
      Southern hybridization revealed that the proportion of the delta F508 mutation
      was 58% in this population, and that the frequency of the B (i.e., KM19/XV2c [1
      2]) haplotype was increased in both delta F508 and non-delta F508 CF chromosomes
      (98% and 46%, respectively). These results support the view that the trans
      European gradient of the delta F508 frequency is of a geographical rather than of
      an ethnic origin, and that in Slavonic populations, there exists an as yet
      unidentified but frequent CF mutation other than delta F508, associated with the
      B haplotype.

PMID- 1376298
TI  - A novel sickle cell mutation of yet another origin in Africa: the Cameroon type.
AB  - The sickle cell mutation (beta s) arose as at least three independent events in
      Africa and once in Asia, being termed the Senegal, Benin, Bantu and Indian types
      respectively. An investigation in Cameroon was carried out to determine whether
      the atypical sickle genes observed in the neighboring countries are the result of
      recombination or the presence of a sickle cell mutation of a different genetic
      origin. It was conducted on 40 homozygous SS patients followed at the Blood
      Transfusion Center in the capital city of Yaounde. On 80 beta s chromosomes, 13
      exhibited a novel polymorphic pattern that was observed three times in the
      homozygous state. This chromosome contains an A gamma T gene. The restriction
      fragment length polymorphism haplotype is different from all the other beta s
      chromosomes in both the 5' and 3' regions, but has previously been reported in
      sporadic cases. The (AT)8(T)5 sequence in the -500 region of the beta gene is
      specific and different from that of the Senegal, Benin, Bantu or Indian beta s
      genes. All the carriers of this specific chromosome belong to the Eton ethnic
      group and originate from the Sanaga river valley. This observation strongly
      argues for yet another independent origin of the sickle cell mutation in Africa,
      here referred to as the "Cameroon type". The Benin haplotype and a Benin/Bantu
      recombinant haplotype have been observed in the other studied populations:
      Ewondo, Bamileke, Bassa, Yambassa and Boulou.

PMID- 1376299
TI  - Immunorecognition of different ganglioside epitopes on human normal and melanoma
      tissues.
AB  - There is increasing evidence that cell-surface gangliosides play a role in tumor
      growth, progression and metastases. In order to determine the frequency of
      ganglioside GD3 in patients with metastatic malignant melanoma for further
      therapeutic trials, GD3 ganglioside expression was determined in 119 tissue
      samples. Of these melanomas, 93% (111/119) were R-24-positive, which indicates
      the value of this diagnostic marker for melanoma. To study the structural
      epitopes of gangliosides, 10 ganglioside antibodies with defined specificities
      and affinities were tested on over 100 fresh-frozen tissue specimens of human
      normal and melanoma tissues. All the antibodies tested recognize the ganglioside
      GD3, but vary in their cross-reactivity with other gangliosides. According to
      their epitope specificity, they can be divided into 5 groups. For example, the
      antibodies Z-21 and A-4 react like the previously established MAb R-24 with
      gangliosides GD3 and GQlb, and one MAb (Q-4) detects all gangliosides containing
      2 connected sialic acids (GD3, GD2, GDlb, GTlb, GQlb). Specificity on TLC does
      not always correlate with specificity to melanoma tissues and vice-versa. For
      example, MAb A-4, which recognizes only GD3 and GQlb on TLC, shows no specific
      reactivity on tissues. Furthermore, antibodies with the same ganglioside
      specificity do not have the same staining pattern on human tissues. For example,
      MAb Z-21, which is directed against the same gangliosides as MAb R-24 on TLC,
      does not cross-react with as many neuroectodermal tissues as MAb R-24. Because of
      their distinct properties, some of these antibodies may be even more useful for
      immunodiagnosis and immunotherapy of malignant melanoma than MAb R-24.

PMID- 1376300
TI  - Studies of clonal cell lines developed from primary breast cancers indicate that
      the ability to undergo morphogenesis in vitro is lost early in malignancy.
AB  - In an attempt to obtain cell lines from the different components found in primary
      breast cancers, we used a low-calcium medium to culture epithelial cells of mixed
      phenotype and a recombinant T antigen containing retrovirus to immortalize cells
      found in these cultures. In each case, the histology of the sample used for
      culture was examined in detail and the best growth was obtained from samples
      associated with a substantial in situ or benign component and from lobular rather
      than ductal carcinomas. Clonal cell lines were developed from each of 4 tumours:
      1 infiltrating ductal (tumour number 2), 2 infiltrating lobular (tumours 3 and 5)
      and 1 mucoid (tumour 6). To try to identify the phenotype and origin of the cell
      lines, immunohistochemical markers, histological analysis of tissue sections and
      behavioural markers were used. All the cell lines expressed mainly luminal
      epithelial cell markers, but the basal epithelial keratin, keratin 14, was also
      expressed homogeneously or heterogeneously. Growth in agar was seen with some but
      not all cell lines derived from only 1 tumour (tumour 5) and tumour development
      in nude mice was observed (with low efficiency) with cell lines from only 1
      tumour (tumour 6). The data suggest that the cell lines obtained from the
      infiltrating ductal carcinoma (tumour 2) developed from cells cultured from the
      associated benign component, while the cell lines from tumours 3, 5 and 6 may
      each have developed from a cell in an early stage of malignancy. When tested for
      their ability to undergo morphogenesis on extracellular matrix components, cell
      lines from tumour 2 made well-developed ductal-alveolar-like structures, while
      those from the other tumours did not.

PMID- 1376301
TI  - Dipyridamole enhances an anti-proliferative effect of interferon in various types
      of human tumor cells.
AB  - The anti-proliferative activity of human interferon (HuIFN) was enhanced by
      dipyridamole, 2,6-bis-(diethanolamino)-4,8-dipiperidinopyrimido-[5,4-d]-py
      rimidine, when tested against various human tumor cell lines, including KT
      (breast carcinoma), PLC/PRF/5 (hepatoma), MGC-I, U251-SP and T98 (glioma), HAC-2
      and SHIN-3 (ovarian carcinoma), and MM-ICB (melanoma). The enhancement occurred
      irrespective of the kind of HuIFN used (alpha, beta or gamma) and the original
      degree of susceptibility of the cells to HuIFN. Even low doses down to 0.01
      microM of dipyridamole that had no intrinsic anti-proliferative activity could
      enhance the effect of HuIFN. The enhancement of HuIFN effects seems not to be
      caused by induction of HuIFN production, because neither anti-viral activity nor
      HuIFN antigens were detected in culture medium in cells treated with
      dipyridamole. Mopidamole, a derivative of dipyridamole lacking one piperidine
      residue, produced little enhancement of the effects of HuIFN. Among ovarian
      cancer cell lines tested, the enhancement of the activity of HuIFN by
      dipyridamole for HAC-2 and SHIN-3 cells was equivalent to or greater than that
      for 3 chemotherapy agents (adriamycin, vincristine, and a camptothecin
      derivative). However, neither HOC-21 ovarian cancer cells nor HEC-1 endometrial
      adenocarcinoma cells were susceptible to any combinations. When MGC-1, U251-SP,
      and HAC-2 cells were injected into nude mice, the growth of tumors was more
      markedly inhibited by the subcutaneous administration of HuIFN in combination
      with oral administration of dipyridamole than by the HuIFN alone. Thus, this
      combination therapy seems to be worth trying for human cancer, although the
      enhancement of the effects of HuIFN by dipyridamole varied among the cell lines
      examined.

PMID- 1376302
TI  - Inhibition of tumor-induced angiogenesis by the administration of recombinant
      interferon-gamma followed by a synthetic lipid-A subunit analogue (GLA-60).
AB  - The effect of the administration of recombinant interferon-gamma (rIFN-gamma) and
      a synthetic lipid A subunit analog (GLA-60) on angiogenesis induced by B16-BL6
      melanoma was examined in syngeneic C57BL/6 mice. Intravenous administration of
      rIFN-gamma followed by GLA-60 (referred to as rIFN-gamma/GLA-60) induced
      endogenous production of tumor necrosis factor (TNF). This treatment on day 3
      after tumor inoculation caused a marked decrease in the number of vessels
      oriented towards the tumor mass (angiogenic response) and tumor size over a
      period of 9 days. In contrast, neither rIFN-gamma nor GLA-60 alone, nor GLA
      60/rIFN-gamma (reverse sequence of administration), which is unable to induce the
      production of TNF in the serum, had any effect. Sera induced by the treatment
      with rIFN-gamma/GLA-60, and recombinant TNF, inhibited the in vitro growth of
      lung endothelial cells which is considered to be one of the essential events in
      tumor neovascularization. Multiple i.v. treatments with rIFN-gamma/GLA-60 on days
      5, 8 and 11 after s.c. implantation of tumor significantly inhibited primary
      tumor growth by the amputation time (day 20) and lung metastasis of B16-BL6 cells
      on day 34, while other treatment modalities had no such effect. Our results
      indicate that inhibition of lung-tumor metastasis by rIFN-gamma/GLA-60 treatment
      may be partly due to the inhibition of tumor-associated angiogenesis.

PMID- 1376303
TI  - The effect of retinoic acid on chemosensitivity of PA-1 human teratocarcinoma
      cells and its modulation by an activated N-ras oncogene.
AB  - Combination of chemotherapeutic drugs with agents that induce cell
      differentiation is a possible means of improving cancer chemotherapy. To explore
      this approach we used 4 cell lines established from the human teratocarcinoma
      derived cell line PA-1; 2 retinoic acid (RA)-sensitive lines compared to 2 RA
      resistant lines transformed by an activated N-ras oncogene. Equal numbers of
      colony-forming cells were exposed for 72 hr to 10(-6)M RA and subsequently to a
      range of concentrations of cisplatinum, etoposide or bleomycin. Enhanced
      cytotoxicity of cisplatin and etoposide (3- to 5-fold) was observed in the N-ras
      transformed cell lines compared to the non-transformed lines. Treatment with RA
      caused an increase in the cytotoxicity of all 3 drugs to the 2 RA-sensitive cell
      lines. In contrast, a reduction of cytotoxicity was observed in the 2 N-ras
      transformed lines. Our results indicate that sensitivity to cytotoxic agents can
      be increased by RA in RA-sensitive cells, but the opposite effect is seen in N
      ras transformed, RA-resistant cells. Therefore, a general rationale for
      combination therapy with RA and cytotoxic drugs cannot be inferred.

PMID- 1376304
TI  - Polymeric microballoons as ultrasound contrast agents. Physical and ultrasonic
      properties compared with sonicated albumin.
AB  - Air-filled polymeric microballoons were prepared with number-mean diameters of
      approximately 3 microns, volume-mean diameters of approximately 5 microns, and
      narrow particle-size distributions (standard deviation [SD] = 1.2 microns in
      number and SD = 2.0 microns in volume). More than 99% of the particles were below
      8 microns. These particles were found to be highly echogenic for ultrasound,
      showing backscatter coefficients at 7.5 MHz, similar to the ones obtained with
      sonicated albumin microspheres. However, at 2.25 MHz, microballoons were less
      echogenic than albumin microspheres. These results are consistent with ultrasound
      attenuation measurements, which showed a maximum at 8 to 9 MHz for the
      microballoons compared with a reported value of 3.5 to 4.5 MHz for albumin
      microbubbles. Polymeric microballoons were found to be stable in plasma or under
      applied pressure as evidenced by unchanged particle concentration and
      echogenicity. Albumin microspheres were particularly unstable to applied pressure
      (150 mm Hg) and showed a rapid decrease in both particle counts and echogenicity.

PMID- 1376305
TI  - Human hematopoietic growth factors.

PMID- 1376306
TI  - Induction chemotherapy in head and neck cancer: results of a phase III trial.
AB  - Between December 1982 and October 1986, 131 patients with stage II-III-IV
      squamous cell carcinoma of the oropharynx or oral cavity were randomized to
      induction chemotherapy, consisting of bleomycin (10 mg/m2/day in continuous
      infusion from day 1 to day 5), methotrexate (120 mg/m2 on day 2) followed by
      folinic acid, 5-fluorouracil (5 FU) (600 mg/m2 on day 2), and cisplatin (120
      mg/m2 on day 4) every 4 weeks for a total of three cycles followed by definitive
      locoregional treatment versus locoregional treatment alone. The modalities of
      definitive treatment (radiotherapy +/- surgery) were chosen prior to
      randomization. A total of 116 patients were evaluable. Of 55 patients in the
      chemotherapy arm, four (7%) had a complete response (CR) and 23 (42%) a partial
      response (PR) following the induction regimen. At the completion of locoregional
      treatment, 76% (42 of 55) of patients in the experimental group were in CR
      compared to 89% (54 of 61) in the control group. There was no difference in
      survival, cause-specific survival, and pattern of relapse between both groups.
      The median survival was 22 months in the chemotherapy group and 29 months in the
      control group. Responders to chemotherapy did not fare better than nonresponders.
      Chemotherapy-related toxicities were few and most of them related to cisplatin
      which was reduced to 100 mg/m2 for 35 patients. There were no treatment-related
      deaths and, in the experimental arm of the trial, no increased morbidity from
      locoregional treatment. This induction regimen does not offer any advantages over
      standard treatment.

PMID- 1376307
TI  - Basal and FSH-stimulated steady state levels of SGP-2, alpha 2-macroglobulin, and
      testibumin in culture media of rat seminiferous tubules at defined stages of the
      epithelial cycle.
AB  - Production of several proteins by rat Sertoli cells is dependent on the stage of
      the cycle of the seminiferous epithelium. The authors have determined steady
      state levels and follicle-stimulating hormone responsiveness of three Sertoli
      cell products in culture media of rat seminiferous tubule segments at different
      stages of the epithelial cycle: SGP-2 (sulfated glycoprotein-2), alpha 2
      macroglobulin, and testibumin. Basal SGP-2 levels were twofold higher in stages
      VII through VIII compared with stages XIII to I to VI (P less than 0.05). Highest
      basal alpha 2-macroglobulin levels were found in stages II through VIII; this was
      about 35% greater than in stages XIII through I of the cycle (P less than 0.05).
      Basal testibumin levels were twofold higher in stages II through VI compared with
      stages IX through XII of the cycle. Follicle-stimulating hormone had no effect on
      SGP-2, but by contrast it (50 mg/L) increased the level of alpha 2-macroglobulin
      significantly (P less than 0.05) in stages XIII through I. Follicle-stimulating
      hormone treatment (10 mg/L) elevated testibumin levels at each stage-pool by
      about 40% (P less than 0.05). The current results using staged tubular segments
      in vitro demonstrate cyclic basal steady-state levels of the three proteins along
      the seminiferous tubules and follicle-stimulating hormone regulation of alpha 2
      macroglobulin and testibumin.

PMID- 1376308
TI  - Epithelial modulation of allergen and drug effects in guinea pig airways.
AB  - The effect of egg albumin (EA) challenge on tracheal tube preparations from
      sensitized guinea pigs was studied with regard to EA permeability, histamine
      release and penetrability, and the contractile response of the preparation. We
      used a plethysmographic method that allowed simultaneous measurement of changes
      in smooth muscle tension and collection of samples for determination of
      mediators. Our results clearly show that epithelial damage potentiates the
      contractile response to histamine, potassium ions, and acetylcholine. Epithelial
      damage did not alter the maximal contractile response in preparations challenged
      with high antigen concentrations (EA, 1 mg/ml), but histamine release measured in
      the perfusate increased substantially. The permeability of the preparations to EA
      was greater when the epithelium was damaged. No increase in the permeability in
      response to the EA challenge was observed. The present study has demonstrated
      that guinea pig airway epithelium constitutes a barrier for both antigen and
      drugs. We also present a method for recording contractile responses from intact
      whole tracheal preparations, in which the epithelium can still act as a barrier,
      as is the case in vivo.

PMID- 1376309
TI  - Induction of atrial natriuretic factor and myosin light chain-2 gene expression
      in cultured ventricular myocytes by electrical stimulation of contraction.
AB  - While hormonal stimuli and mechanical stretch can induced cardiac-specific gene
      expression and in some cases cellular hypertrophy, the relationship between
      myocyte contraction frequency, gene expression, and myocyte growth has not been
      well characterized. In this study a new model system was developed in which
      cultures of neonatal rat ventricular myocytes were subjected to long term pacing
      of contractions with pulsatile electrical stimulation. Myocytes submitted to
      electrical stimulation for 3 days displayed dramatic increases in cellular size
      and myofibrillar organization, and a 5-10-fold increase in the expression of the
      cardiac genes atrial natriuretic factor and myosin light chain-2. Atrial
      natriuretic factor expression induced by electrical stimulation of contractions
      was inhibited by nifedipine or W7, indicating a dependence on calcium influx and
      calmodulin activity. Phosphoinositide hydrolysis and cAMP formation were not
      affected by electrical stimulation suggesting that gene induction occurred
      independently of the activation of protein kinases C or A above basal levels.
      These findings show that the cellular events associated with contraction, such as
      changes in cytoplasmic free calcium levels and/or cellular stretch, may serve as
      important determinants of myocyte growth and cardiac gene expression.

PMID- 1376310
TI  - A peptide corresponding to GPIIb alpha 300-312, a presumptive fibrinogen gamma
      chain binding site on the platelet integrin GPIIb/IIIa, inhibits the adhesion of
      platelets to at least four adhesive ligands.
AB  - The platelet fibrinogen (Fg) receptor (GPIIb/IIIa) is an integrin which plays a
      critical role in hemostasis by recognizing at least the four adhesive ligands:
      Fg, fibronectin (Fn), vitronectin (Vn), and von Willebrand factor (vWf). We
      reported that residues 309-312 of GPIIb alpha appear to comprise at least part of
      a Fg binding site on the Fg receptor (Gartner, T. K., and Taylor, D. B. (1990)
      Thromb. Res. 60, 291-309). Here we report that the peptide GPIIb alpha 300-312
      (G13) inhibits platelet aggregation and binds Fg and Vn. Significantly, this
      peptide inhibits the adhesion of stimulated platelets to Fg, Fn, Vn, and vWf, but
      not the adhesion of resting platelets to Fn. Thus, GPIIb 300-312 may constitute a
      specific but common recognition site on GPIIb/IIIa for both LGGAKQAGDV- and RGD
      containing ligands.

PMID- 1376311
TI  - Kinetics of inhibition of endogenous human immunodeficiency virus type 1 reverse
      transcription by 2',3'-dideoxynucleoside 5'-triphosphate, tetrahydroimidazo
      [4,5,1-jk][1,4]-benzodiazepin-2(1H)-thion e, and 1-[(2-hydroxyethoxy)methyl]-6
      (phenylthio)thymine derivatives.
AB  - Recently, tetrahydroimidazo-[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and -thione
      (TIBO) and 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) compounds
      have been shown to be potent, selective, and specific inhibitors of human
      immunodeficiency virus type 1 (HIV-1) replication in vitro. They interact with
      the reverse transcriptase of HIV-1 in a way different from that of previously
      studied reverse transcriptase (RT) inhibitors. We established an endogenous RT
      assay, starting from intact HIV-1 virions. This assay mimics the reverse
      transcription process in the HIV-infected cell more closely than RT assays with
      artificial templates. We investigated the inhibition of endogenous HIV-1 reverse
      transcription by the TIBO derivative (+)-(S)-4,5,6,7-tetrahydro-5-methyl-6-(3
      methyl-2-butenyl)imidazo [4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (R-82150) in
      comparison with the HEPT derivative 5-ethyl-1-ethoxymethyl-6-(phenylthio)uracil
      (E-EPU) and 2',3'-dideoxyguanosine 5'-triphosphate. The kinetics and
      characteristics of RT inhibition by TIBO in the endogenous RT assay were similar
      to those found previously for the exogenous RT assay (following addition of
      exogenous template/primer); thus, RT inhibition by TIBO was specific for HIV-1
      and the extent of RT inhibition was dependent on which of the four substrates
      (dATP, dTTP, dGTP, and dCTP) was present in limited concentrations. Of the three
      enzymatic activities, RNA-dependent DNA polymerization was preferentially
      inhibited, and inhibition was not competitive with respect to the natural
      substrates. HIV-1 RT behaved as an allosteric enzyme, which means that positive
      cooperativity for binding of the substrate was observed. TIBO behaved as an
      allosteric inhibitor by causing a concentration-dependent decrease in this
      cooperativity.

PMID- 1376312
TI  - Desensitization of the human V2 vasopressin receptor. Homologous effects in the
      absence of heterologous desensitization.
AB  - Three main pathways have been implicated in desensitization of receptors that
      stimulate adenylylcyclase (AC): cAMP-mediated phosphorylation; cAMP-independent
      phosphorylation, and receptor internalization. Cell lines derived from the murine
      Ltk- cell were found useful in exploring the contribution of cAMP-dependent
      phosphorylation in V2 vasopressin receptor desensitization. The HTB-2 cell
      expresses the human V2 vasopressin receptor, introduced by transfection of human
      genomic DNA, and the prostaglandin E1 (PGE1) receptor, endogenous to the Ltk-
      cell. The A7 cell expresses the hamster beta 2-adrenoceptor, which undergoes the
      above-mentioned desensitization processes. Treatment of HTB-2 cells with arginine
      vasopressin (AVP) had no effect on AC responsiveness to PGE1, but promoted
      desensitization of the AVP response. This was seen as a 5-6-fold right shift in
      the dose-response curves for AVP action (cAMP accumulation in intact cells and AC
      stimulation in homogenates and isolated membranes) and in a decrease in the
      maximum effect of AVP on these parameters. AVP treatment caused a decrease in
      cell surface receptors to approximately 75% of control without changes in KD, as
      determined by Scatchard analysis. When cAMP was increased by treatment with 10
      microM PGE1 and isobutylmethylxanthine, desensitization of the PGE1 receptor was
      observed but not of the AVP receptor. In A7 cells the same treatment caused, as
      expected, a 3-fold right shift in the dose-response curve for AC stimulation by
      isoproterenol, indicating that L cells can mediate heterologous desensitization.
      These data demonstrate that the V2 vasopressin and the PGE1 receptors undergo
      homologous desensitization in the absence of cAMP-mediated phosphorylation and
      that this component is not required for vasopressin receptor internalization.

PMID- 1376313
TI  - High affinity inhibition of Ca(2+)-dependent K+ channels by cytochrome P-450
      inhibitors.
AB  - The Ca(2+)-dependent K+ channel of human red cells was inhibited with high
      affinity by several imidazole antimycotics which are potent inhibitors of
      cytochrome P-450. IC50 values were (in microM): clotrimazole, 0.05; tioconazole,
      0.3; miconazole, 1.5; econazole, 1.8. Inhibition of the channel was also found
      with other drugs with known cytochrome P-450 inhibitory effect. However, no
      inhibition was obtained with carbon monoxide (CO). This suggests that, given the
      high selectivity of the above inhibitors for the heme moiety, a different but
      closely related to cytochrome P-450 kind of hemoprotein may be involved in the
      regulation of the red cell Ca(2+)-dependent K+ channel. Clotrimazole also
      inhibited two other charybdotoxin-sensitive Ca(2+)-dependent K+ channels, those
      of rat thymocytes (IC50 = 0.1-0.2 microM) and of Ehrlich ascites tumor cells
      (IC50 = 0.5 microM). Imidazole antimycotics inhibit also receptor-operated Ca2+
      channels (Montero, M., Alvarez, J. and Garcia-Sancho, J. (1991) Biochem. J. 277,
      73-79). This suggests that both Ca2+ and Ca(2+)-dependent K+ channels might have
      a similar regulatory mechanism involving a cytochrome.

PMID- 1376314
TI  - Kinetics of inhibition of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase by the novel HIV-1-specific nucleoside analogue [2',5'-bis-O-(tert
      butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro-5 "- (4"-amino-1",2"-oxathiole
      2",2"-dioxide)thymine (TSAO-T).
AB  - [2',5'-Bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3'-spiro- 5"-(4"
      amino-1",2"-oxathiole-2", 2"-dioxide)thymine (TSAO-T) is a representative of a
      novel class of nucleoside analogues that are endowed with a potent and specific
      activity against human immunodeficiency virus (HIV) type 1 and are targeted at
      the HIV-1 reverse transcriptase (RT). Inhibition of HIV-1 RT by TSAO-T was
      reversible and noncompetitive with respect to dGTP as the substrate and
      poly(C).oligo(dG) as the template/primer. In contrast with the nonnucleoside
      derivatives tetrahydroimidazo-[4,5,1-jk][1,4]- benzodiazepin-2(1H)-thione (TIBO)
      (R-82150), nevirapine (BI-RG-587) and the HEPT derivative I-HEPU-SdM, TSAO-T was
      not inhibitory to HIV-1 RT in the presence of other homopolymeric
      template/primers. It did not interfere with the DNA-dependent DNA polymerase
      function of HIV-1 RT, HIV-2 RT, herpes simplex virus type 1 DNA polymerase, or
      Taq polymerase. However, TSAO-T proved inhibitory to the HIV-1 RT reaction primed
      by Escherichia coli 16S/23S rRNA, irrespective of the nature of the radiolabeled
      2'-deoxynucleotide 5'-triphosphate (dNTP) used. TSAO-T does not act as a DNA
      chain terminator. It interacts with HIV-1 RT at a nonsubstrate (dNTP)-binding
      site.

PMID- 1376315
TI  - Identification of the forms of insulin-like growth factor-binding proteins
      produced by human fibroblasts and the mechanisms that regulate their secretion.
AB  - Human fibroblasts secrete insulin-like growth factor-binding proteins (IGFBPs)
      that can modify insulin-like growth factor (IGF) I action. We have determined the
      molecular identities of three forms of IGFBPs that are secreted by human
      fibroblasts in vitro. Ligand blot analysis of fibroblast conditioned media
      revealed that the M(r) 43,000 and 39,000 forms were the most abundant, but that
      M(r) 31,000 and 24,000 forms were also present. An antiserum that was specific
      for IGFBP-5 reacted with the M(r) 31,000 form, and an IGFBP-4-specific antiserum
      recognized only the M(r) 24,000 form. The M(r) 39,000 and 43,000 forms were
      detected by IGFBP-3 antiserum. Further proof that fibroblasts synthesized these
      forms of IGFBPs was obtained by Northern blotting. A cDNA probe for IGFBP-3
      hybridized with a 2.4-kilobase (kb) transcript, whereas a cDNA probe for IGFBP-5
      recognized a single 6.0-kb transcript, and an IGFBP-4 cDNA probe recognized 2.2-
      and 2.0-kb transcripts. IGF-I and -II caused a minimal (less than 43%) increase
      in IGFBP-5 mRNA abundance and had no effect on IGFBP-4 mRNA abundance. IGF-I and 
      II (100 ng/ml) stimulated 6-8-fold increases in IGFBP-5 levels, whereas IGFBP-4
      was inhibited. Insulin failed to elicit any change in IGFBP-5, suggesting that
      binding of the IGFs to IGFBPs was required to detect the increase. Immunoblotting
      for IGFBP-5 revealed an M(r) 23,000 (non-IGF-I-binding) fragment. To determine if
      the IGFs were influencing proteolytic degradation of IGFBP-5, pure IGFBP-5 was
      added to fibroblast cultures and incubated for 4 h at 37 degrees C. The amount of
      fragment formation was attenuated by the presence of IGF-I and -II, but not
      insulin, suggesting that this is a mechanism by which the IGFs act to modulate
      IGFBP-5 concentration. In contrast to the IGFs, forskolin, which increased IGFBP
      4 and -5 mRNA abundance and secretion, had no effect on fragment formation. The
      results show that human fibroblasts synthesize and secrete IGFBP-3, -4, and -5
      and that changes in intracellular cAMP regulate synthesis, whereas the IGFs
      regulate IGFBP-4 and -5 levels by post-transcriptional mechanisms.

PMID- 1376317
TI  - Mapping of binding sites for heparin, plasminogen activator inhibitor-1, and
      plasminogen to vitronectin's heparin-binding region reveals a novel vitronectin
      dependent feedback mechanism for the control of plasmin formation.
AB  - Vitronectin (VN) has been implicated as a major matrix-associated regulator
      component of plasminogen activation by serving as a potent stabilizing cofactor
      of plasminogen activator inhibitor-1 (PAI-1). The direct binding of heparin,
      plasminogen as well as PAI-1 in its latent and active form to immobilized VN was
      studied in the absence or presence of competitors. Monoclonal antibodies against
      the carboxyl-terminal portion of VN inhibited both PAI-1 and plasminogen binding,
      whereas heparin, heparan sulfate with a high degree of sulfation, or dextran
      sulfate interfered with PAI-1 binding (KD = 20 nM) only. Utilizing synthetic
      peptides encompassing overlapping sequences of the heparin-binding domain of VN,
      adjacent heparin and PAI-1-binding sites were localized within the sequence 348
      370 of VN. Although a number of other serine protease inhibitors which do not
      form binary complexes with VN contain a reactive-site Ser at their P1'-position,
      a reactive-site P1' mutant of PAI-1 (Met----Ser) showed comparable if not
      increased binding to VN. Binding of Lys-plasminogen and active-site-blocked
      plasmin was at least 10-fold higher in affinity (KD = 85-100 nM) compared to Glu
      plasminogen (KD approximately 1 microM) and could be inhibited by lysine analogs
      but not by glycosaminoglycans or PAI-1, indicating that heteropolar plasmin(ogen)
      binding of VN occurs to an adjacent segment upstream to the heparin and PAI-1
      binding sites. This contention was further supported in binding studies with
      plasmin-modified VN which lost both heparin and PAI-1 binding but exhibited 2-3
      fold higher capacity to bind plasminogen. The essential plasmin(ogen)-binding
      site was mapped by ligand blot analysis to the carboxyl-terminal portion of
      proteolytically trimmed VN (M(r) = 61,000). Moreover, treatment of the
      extracellular matrix of human umbilical vein endothelial cells with plasmin
      resulted in partial degradation of matrix-associated VN and concomitant release
      of PAI-1, but increased the ability of the matrix by about 2-fold to bind
      plasminogen. These results are indicative of differential interactions of VN with
      components of the plasminogen activation system, whereby plasmin itself may
      provoke the switch of VN from an anti-fibrinolytic into a pro-fibrinolytic
      cofactor. This process reflects a novel role for the adhesive protein and its
      degradation product(s) in the possible feedback regulation of localized plasmin
      formation at extracellular sites.

PMID- 1376316
TI  - Immunoglobulin-mediated phagocytosis by human monocytes requires protein kinase C
      activation. Evidence for protein kinase C translocation to phagosomes.
AB  - This study has investigated the role of protein kinase C (PKC) activation in IgG
      mediated phagocytosis by human monocytes. Incubation of monocytes with IgG
      opsonized targets increased membrane-associated PKC approximately 2-fold. Kinetic
      studies showed that the translocation of PKC to membrane occurred before
      significant ingestion took place. The pharmacologic PKC inhibitor H7 inhibited
      IgG-dependent ingestion with ID50 of 20 microM, while the structurally related
      isoquinoline sulfonamide HA1004 had no effect at this concentration.
      Staurosporine and calphostin C, PKC inhibitors which have different mechanisms of
      actions than H7, also inhibited ingestion. Depletion of PKC by prolonged
      incubation with phorbol esters also inhibited phagocytosis, and dose-response
      curves showed a strong correlation between the extent of PKC depletion and the
      extent of inhibition of ingestion. Finally, phagosomes were isolated by sucrose
      density centrifugation of cells disrupted 5 min after the initiation of
      phagocytosis. Measurement of PKC activity and immunoreactivity in the phagosomes
      showed that PKC was concentrated in the phagosome membrane approximately 5-fold
      compared to the uninvolved plasma membrane. Together, these data suggest that PKC
      activation is an early, essential step in the efficient ingestion of IgG
      opsonized targets by monocytes.

PMID- 1376318
TI  - The alpha-operon equivalent genome region in the extreme halophilic
      archaebacterium Haloarcula (Halobacterium) marismortui.
AB  - The genome region of the extreme halophilic archaebacterium Haloarcula
      marismortui equivalent to the alpha-operon of Escherichia coli has been
      characterized. In H. marismortui, the alpha-operon was found to be located
      immediately upstream from the S9 gene cluster. The gene order in the
      halobacterial alpha-operon, given according to the gene products, is tRNA(Ser),
      HmaS13, HmaS4, HmaS11, and HmaRp alpha. Compared to the corresponding operon from
      E. coli, the halobacterial gene organization differs in (i) the presence of a
      gene for tRNA(Ser) (GCU), (ii) the reversed order of the genes for the ribosomal
      proteins HmaS11 and HmaS4, and (iii) the absence of the gene coding for the
      ribosomal protein L17. The primary structure of HmaRp alpha shows high similarity
      to a subunit of eukaryotic RNA polymerase II (YeaRpB3, HsaRpB33), whereas the
      similarity to the eubacterial alpha-subunit of RNA polymerase is only weak.

PMID- 1376319
TI  - Gene and pseudogene of the mouse cation-dependent mannose 6-phosphate receptor.
      Genomic organization, expression, and chromosomal localization.
AB  - The cation-dependent mannose 6-phosphate receptor (CD-MPR) is one of the two
      transmembrane proteins involved in transport of lysosomal enzymes. We have cloned
      the mouse CD-MPR gene and also a very unusual processed-type CD-MPR pseudogene.
      They are both present at one copy per haploid genome and map to chromosomes 6 and
      3, respectively. Comparison of the complete 10-kilobase (kb) sequence of the
      functional gene with the cDNA indicates that it contains seven exons. Exon 1
      encodes the 5'-untranslated region of the mRNA, the others (exons 2-7) encode the
      luminal, transmembrane, and cytoplasmic domains of the CD-MPR. Exon 7 also
      contains a 1.2-kb-long 3'-untranslated region of the mRNA. A unique transcription
      initiation site was determined by primer extension of mouse liver mRNA. The
      promoter elements in the 5' upstream region of this site resemble those contained
      in genes constitutively transcribed. However, Northern blot analysis demonstrates
      that the CD-MPR is variably expressed in adult mouse tissues and during mouse
      development. The pseudogene, which is flanked by direct repeats, is almost
      colinear with the cDNA indicating that it presumably arose by reverse
      transcription of an mRNA. However, the pseudogene differs from the cDNA. It
      contains at its 5' end, an additional 340-nucleotide (nt) sequence homologous to
      the promoter region of the functional gene. This sequence exhibits some promoter
      activity in vitro. Furthermore, a 24-nt insertion interrupts the region
      homologous to the 5'-noncoding region of the cDNA. In the functional gene, this
      24-nt sequence occurs between exon 1 and 2, where it is flanked by typical
      consensus sequences of exon/intron boundaries. Therefore, it may represent an
      additional exon of the functional gene. These two features of the pseudogene
      suggest that expression of the CD-MPR gene may be regulated by use of different
      promoters and/or alternative splicing.

PMID- 1376320
TI  - Replacement of negative by positive charges in the presumed membrane-inserted
      part of diphtheria toxin B fragment. Effect on membrane translocation and on
      formation of cation channels.
AB  - Diphtheria toxin B fragment is capable of forming cation-selective channels in
      the plasma membrane. Such channels may be involved in the translocation of the
      toxin A fragment to the cytosol. Seven negatively charged amino acids in the B
      fragment were replaced one by one by lysines, followed by studies of cytotoxicity
      and channel-forming ability of the different mutants. The mutant D392K showed a
      strong reduction in binding to cell surface receptors. Of the six mutants that
      showed wild-type binding affinity, the two mutants D295K and D318K were very
      inefficient in forming channels. These two mutants had the lowest ability to
      mediate A fragment translocation. The mutant E362K was able both to induce cation
      channel formation and to mediate A fragment translocation at a higher pH value
      than the wild-type B fragment. The results support the notion that formation of
      cation channels is of importance for the translocation of the A fragment across
      the plasma membrane, and they indicate that the pH requirement for translocation
      of the A fragment to the cytosol is partly determined by the B fragment.

PMID- 1376321
TI  - Analysis of the importance of arginine 102 in neutral endopeptidase
      (enkephalinase) catalysis.
AB  - Neutral endopeptidase 24.11 contains an active site arginine believed to function
      in substrate binding. This arginine is thought to form an ionic interaction with
      the COOH-terminal carboxylate of NEP substrates. The functionality of arginine
      102 has been investigated by using site-directed mutagenesis to produce mutants
      in which this residue was converted to a lysine, glycine, glutamine, or
      glutamate. All of the mutants exhibited essentially full activity as determined
      with a synthetic peptide amide, glutaryl-Ala-Ala-Phe-4-methoxy-2-naphthylamide.
      In contrast, activity was detected only with the wild-type enzyme and the lysine
      mutant using a synthetic substrate containing a free COOH-terminal carboxylate,
      dansyl-Gly-Trp-Gly. Inhibition studies with the physiologically active peptide
      substrates substance P, endothelin, and angiotensin I, as well as substance P
      free acid, [D-Ala2,Leu5]enkephalin, and [D-Ala2,Leu5]enkephalinamide indicated a
      lack of importance of arginine 102 in substrate binding. With [D
      Ala2,Met5]enkephalin and the chemotactic peptide, N-formyl-Met-Leu-Phe, a
      significant decrease in affinity is observed with the arginine 102 mutants. These
      results suggest that the contribution of arginine 102 to substrate binding is
      dependent upon the strength of other subsite interactions. Examination of
      dipeptides as inhibitors indicates that the nature and orientation of the P'2
      residue is important in determining the strength of the interaction of arginine
      102 with its substrates.

PMID- 1376322
TI  - Influence of subunit-specific antibodies on the activity of the F0 complex of the
      ATP synthase of Escherichia coli. I. Effects of subunit b-specific polyclonal
      antibodies.
AB  - Incubation of F1-stripped everted membrane vesicles with antibodies against
      subunit b of the ATP synthase from Escherichia coli resulted in an inhibition of
      the binding of F1 to F0, whereas the proton translocation remained unaffected.
      Incubation of unstripped everted membrane vesicles with anti-b antibodies
      resulted in a partial loss of F1, and the remaining membrane-bound ATP
      hydrolyzing activity is uncoupled from proton translocation. Similar results were
      obtained when F(ab')2 or Fab fragments were used. The immunoblot analysis of
      truncated b' subunits different in length showed that the antigenic determinants
      are located in the carboxyl-terminal half of the polypeptide chain.

PMID- 1376323
TI  - Influence of subunit-specific antibodies on the activity of the F0 complex of the
      ATP synthase of Escherichia coli. II. Effects of subunit c-specific polyclonal
      antibodies.
AB  - After incubation of F1-stripped everted membrane vesicles with antibodies against
      subunit c of the ATP synthase of Escherichia coli the proton translocation
      through the open F0 channel was blocked. Rebinding of F1 to those vesicles is
      affected by the antibody concentration used. In general, the use of F(ab')2 or
      Fab fragments prepared from anti-c antibodies gave similar results. However,
      using Fab fragments a higher amount of antigenic binding sites was necessary to
      block the F0 complex completely, whereas extremely low amounts of Fab fragments
      were necessary to inhibit the binding of F1. This can be explained by an
      antigenic determinant of subunit c, which is only accessible to the smaller Fab
      fragments with a molecular mass of approximately 50,000. Incubation of F1
      containing everted membranes with anti-c antibodies showed that the binding of
      the antibodies resulted in a displacement of F1, while simultaneously the proton
      translocation through F0 has been blocked. Such a displacement can only be
      observed after incubation with IgG molecules or F(ab')2 fragments. Fab fragments
      were not able to displace the F1 part, indicating that the ability of antibodies
      and F(ab')2 fragments to produce cross-links is responsible for the loss of F1
      from the membranes.

PMID- 1376324
TI  - Identification of a factor in fetal bovine serum that stabilizes the cumulus
      extracellular matrix. A role for a member of the inter-alpha-trypsin inhibitor
      family.
AB  - Fetal bovine serum (FBS) has been widely used in the culture of cumulus-oocyte
      complexes, since it is believed that FBS stabilizes the expanding cumulus
      extracellular matrix. In this study, we have identified a factor in FBS that is
      responsible for this effect. FBS was first fractionated by stepwise precipitation
      with ammonium sulfate followed by high performance liquid chromatography (HPLC)
      on a gel filtration column. Active fractions, as determined by their ability to
      stabilize the cumulus extracellular matrix in a bioassay system, were further
      purified by HPLC on DEAE ion-exchange and gel filtration columns. The purified
      factor was exhibited as a single band on sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis with an apparent Mr 150,000 and a single peak on a C-8
      reverse-phase HPLC. The sequence of the first 14 NH2-terminal amino acids was
      determined by Edman degradation, revealing significant sequence identity of the
      bovine serum factor with the light chain shared by members of the inter-alpha
      trypsin inhibitor family. Western blot analysis using anti-human I alpha I IgG
      shows that the antibody reacts positively with the purified factor, and
      immunodepletion of FBS with anti-I alpha I antibody agarose eliminated its
      ability to stabilize the extracellular matrix. This factor is found in mouse
      follicular fluid collected 6 h following human chorionic gonadotropin injection
      to stimulate ovulation, but not in unstimulated mice. Anti-I alpha I-positive
      epitopes were also localized within the cumulus extracellular matrix of mouse
      preovulatory follicles in immunocytochemical preparations using anti-human I
      alpha I IgG, supporting the possibility that this molecule or molecules may
      diffuse into follicular fluid after an ovulatory stimulus to act as structural
      linkers that ensure normal cumulus expansion, through stabilization of the
      cumulus extracellular matrix thus supporting the process of ovulation.

PMID- 1376325
TI  - Albumin-binding surfaces for implantable devices.
AB  - Surfaces of implantable and blood contact-devices accumulate adsorbed and
      denatured proteins. This anomalous layer of proteins may help trigger unwanted
      events such as activation of coagulation systems and, perhaps, chronic
      inflammation. Because, in many experimental systems, the purposeful coating of
      surfaces with albumin will biologically "passivate" materials, we have attempted
      to develop polymers which, when exposed to blood or body fluids, will
      spontaneously, selectively, and reversibly adsorb host albumin. We report here a
      novel derivatization technique for increasing the albumin affinity of implantable
      polyetherurethane (PU). The technique is based on the incorporation of high
      molecular-weight dextran to which the albumin-binding dye Cibacron Blue is
      covalently attached. Somewhat surprisingly, the amounts of human albumin adsorbed
      by Blue Dextran-modified and unmodified PU are quite similar. There are, however,
      important differences. First, the binding of albumin to derivatized PU is
      specific and not readily blocked by proteins in albumin-depleted human serum.
      Second, the majority of albumin associated with derivatized PU appears to be
      reversibly bound. Third, the binding of albumin to derivatized PU evidently is
      mediated primarily through ligand-specific binding of the protein to the albumin
      binding dextran-dye conjugate. We conclude that it is possible to produce
      implantable polymers having surfaces which display albumin-binding dyes that
      selectively and reversibly bind albumin. Materials with this property, when
      implanted or exposed to blood, should form an infinitely renewable coating of
      albumin derived from physiologic fluids. This surface modification strategy may
      spawn a new generation of implantable materials with improved biologic
      compatibility.

PMID- 1376326
TI  - Situational variation in problem behavior at home and school in attention deficit
      disorder with hyperactivity: a factor analytic study.
AB  - The present investigation assesses situational variation in problem behaviors of
      children with Attention Deficit Disorder with Hyperactivity. Principal-component
      factors (VARIMAX rotation) were computed for the Home/School Situations
      Questionnaires (HSQ/SSQ). For the HSQ, four factors emerged, accounting for 61%
      of variance. For the SSQ, three factors emerged, accounting for 68% of variance.
      Factors were similar to those previously derived with non-referred children. To
      assess discriminative power, factors were compared (t-tests) to previous data.
      All factors significantly discriminated ADD/H from non-referred children. These
      data suggest the factors add to the utility of the HSQ/SSQ in assessing ADD/H.

PMID- 1376327
TI  - Listening preferences in regard to speech in four children with developmental
      disabilities.
AB  - In a previous experimental study of children's listening responses in regard to
      speech sounds, autistic children showed preferential patterns which were in sharp
      contrast to a group of mentally-handicapped and normally-developing children. The
      present study reports the data obtained for four children whose clinical
      diagnosis (1) became available only some time after the study was carried out,
      and/or (2) differed from previously recorded clinical impressions. The results
      obtained support previous findings according to which a lack of attraction to
      speech sounds appears to be a feature of young autistic children's overall
      disregard to people. The present technique is discussed as a viable method to
      examine experimentally young autistic children's social unresponsiveness.

PMID- 1376328
TI  - Induction of active and adoptive relapsing experimental autoimmune
      encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein.
AB  - Proteolipid protein (PLP) is a major component of the central nervous system
      (CNS) myelin membrane and has been shown to induce acute experimental autoimmune
      encephalomyelitis (EAE) in genetically susceptible animals. Here we describe
      conditions by which a relapsing-remitting form of EAE can be reliably induced in
      SJL/J mice either actively immunized with the major encephalitogenic PLP peptide,
      PLP13-151(S), or following adoptive transfer of PLP139-151(S)-specific T cells.
      The disease follows a reliable relapsing-remitting course with acute clinical
      signs first appearing 6-20 days after priming or transfer and relapses first
      appearing at 30-45 days. The initial onset of disease correlates with delayed
      type hypersensitivity (DTH) reactivity specific for PLP139-151(S), in the
      apparent absence of T cell reactivity to the major myelin basic protein (MBP)
      peptide. Histologically, both the active and adoptive forms of the disease are
      characterized by extensive mononuclear cell infiltration and severe demyelination
      of the CNS. These results suggest that T cell responses specific for PLP139
      151(S) are sufficient to induce clinical and histological R-EAE in SJL/J mice.
      This model should prove useful for examination of the cellular and molecular
      events involved in clinical relapses and perhaps in determining the role of PLP
      specific T cell responses in multiple sclerosis (MS).

PMID- 1376329
TI  - Human piebald trait resulting from a dominant negative mutant allele of the c-kit
      membrane receptor gene.
AB  - Human piebald trait is an autosomal dominant defect in melanocyte development
      characterized by patches of hypopigmented skin and hair. Although the molecular
      basis of piebaldism has been unclear, a phenotypically similar "dominant
      spotting" of mice is caused by mutations in the murine c-kit protooncogene. In
      this regard, one piebald case with a point mutation and another with a deletion
      of c-kit have been reported, although a polymorphism or the involvement of a
      closely linked gene could not be excluded. To confirm the hypothesis that
      piebaldism results from mutations in the human gene, c-kit exons were amplified
      by polymerase chain reaction from the DNA of 10 affected subjects and screened
      for nucleotide changes by single-stranded conformation polymorphism analysis. In
      one subject with a variant single-stranded conformation polymorphism pattern for
      the first exon encoding the kinase domain, DNA sequencing demonstrated a missense
      mutation (Glu583----Lys). This mutation is identical to the mouse W37 mutation
      which abolishes autophosphorylation of the protein product and causes more
      extensive depigmentation than "null" mutations. In accord with this "dominant
      negative" effect, the identical mutation in this human kindred is associated with
      unusually extensive depigmentation. Thus, the finding of a piebald subject with a
      mutation that impairs receptor activity strongly implicates the c-kit gene in the
      molecular pathogenesis of this human developmental defect.

PMID- 1376330
TI  - Distinction of human immunodeficiency virus type 1 neutralization and infection
      enhancement by human monoclonal antibodies to glycoprotein 120.
AB  - There is increasing evidence that sera from HIV-1-infected individuals contain
      antibodies that enhance infection by HIV-1 in vitro. Previous work has
      demonstrated that complement receptors on T lymphoid cells and Fc receptors for
      IgG (Fc gamma R) on monocytic cells are required for enhanced infection by
      antibody-complexed HIV-1. Characterization of such infection-enhancing antibodies
      is essential because immunogenic epitopes which induce enhancing antibodies
      should be excluded from HIV-1 vaccines. This study was conducted to identify
      enhancing antibodies involved in Fc R-mediated enhancement of HIV-1 infection
      employing IgG human monoclonal antibodies (HMAbs) reactive against gp120 of HIV
      1, which were produced by B cell lines derived from an HIV-1-infected individual.
      A potent neutralizing HMAb N70-1.5e did not enhance infection by HIV-1 (IIIB and
      MN strains), whereas HMAb N70-2.3a mediated enhancement of HIV-1 infection, but
      had little neutralizing activity. A competition radio immunoassay demonstrated
      that the two antibodies bind to distinct epitopes. These results indicated that
      enhancing and neutralizing antibodies can be induced by different epitopes on
      gp120, suggesting the potential for development of safe vaccines against HIV-1 by
      exclusion of immunogenic epitopes for enhancing antibodies. We made attempts to
      identify the epitope on gp120 that is recognized by the enhancing antibody N70
      2.3a by using recombinant HIV-1 proteins and found that the antibody binds to a
      conformational site of nonvariable sequences in the carboxyl half (aa 272-509) of
      gp120.

PMID- 1376331
TI  - Involvement of integrin alpha V gene expression in human melanoma tumorigenicity.
AB  - Human melanoma originates in the skin and can lead to wide-spread metastatic
      disease. Analysis of melanoma biopsy material has shown that the vitronectin
      receptor, integrin alpha v beta 3, is a specific marker of the most malignant
      cells, i.e., vertically invasive primary lesions or distant metastases (Albelda,
      S. M., S. A. Mette, D. E. Elder, R. Stewart, L. Damjanovich, M. Herlyn, and C. A.
      Buck. 1990. Cancer Res. 50:6757-6764), suggesting a role for this adhesion
      receptor in the malignant growth of human melanoma tumors. A cell model was
      established to analyze the role of alpha v integrins on the tumorigenicity of
      human melanoma. From M21 human melanoma cells, stable variants were selected that
      lack alpha v gene expression and thus fail to express integrin alpha v beta 3
      (M21-L cells). These cells not only lost the ability to attach to vitronectin but
      showed a dramatic reduction in tumorigenicity when transplanted into athymic nude
      mice, compared with M21 cells, even though both cell types showed identical beta
      1 integrin expression and growth properties in vitro. M21-L cells were stably
      transfected with a cDNA-encoding alpha v. This resulted in the functional
      expression of integrin alpha v beta 3 on these cells and completely restored
      their tumorigenicity. Thus, integrin alpha v gene expression and the resulting
      adhesive phenotype are directly involved in the proliferation of human melanoma
      in vivo.

PMID- 1376332
TI  - Unique region of the minor capsid protein of human parvovirus B19 is exposed on
      the virion surface.
AB  - Capsids of the B19 parvovirus are composed of major (VP2; 58 kD) and minor (VP1;
      83 kD) structural proteins. These proteins are identical except for a unique 226
      amino acid region at the amino terminus of VP1. Previous immunization studies
      with recombinant empty capsids have demonstrated that the presence of VP1 was
      required to elicit virus-neutralizing antibody activity. However, to date,
      neutralizing epitopes have been identified only on VP2. Crystallographic studies
      of a related parvovirus (canine parvovirus) suggested the unique amino-terminal
      portion of VP1 assumed an internal position within the viral capsid. To determine
      the position of VP1 in both empty capsids and virions, we expressed a fusion
      protein containing the unique region of VP1. Antisera raised to this protein
      recognized recombinant empty capsids containing VP1 and VP2, but not those
      containing VP2 alone, in an enzyme-linked immunosorbent assay. The antisera
      immunoprecipitated both recombinant empty capsids and human plasma-derived
      virions, and agglutinated the latter as shown by immune electron microscopy. The
      sera contained potent neutralizing activity for virus infectivity in vitro. These
      data indicate that a portion of the amino terminus of VP1 is located on the
      virion surface, and that this region contains intrinsic neutralizing
      determinants. The external location of the VP1-specific tail may provide a site
      for engineered heterologous epitope presentation in novel recombinant vaccines.

PMID- 1376333
TI  - The ability of gingival crevicular fluid acute phase proteins to distinguish
      healthy, gingivitis and periodontitis sites.
AB  - 3 acute phase proteins, from the local gingival inflammatory response, were
      examined for their ability to distinguish healthy, gingivitis and periodontitis
      sites. Indirect competitive immunoassays were developed for the quantification of
      alpha 2-macroglobulin (alpha 2-M) and transferrin (TF), and for alpha 1
      antitrypsin (alpha 1-AT), a double antibody sandwich assay was produced. Healthy
      (25), gingivitis (31) and periodontitis (28) sites were sampled with filter paper
      strips (2 x 13 mm) and the volume assessed with the Periotron 6000. The samples
      were eluted in phosphate-buffered saline and analyzed for alpha 2-M, alpha 1-AT
      and TF. The results were expressed as absolute amounts per sample (ng/30 s) and
      on a concentration basis (ng/microliter of GCF). Higher GCF absolute amounts of
      alpha 2-M, alpha 1-AT and TF were consistently obtained from diseased (gingivitis
      and periodontitis) sites than healthy sites (p less than 0.005). Absolute amounts
      of GCF alpha 2-M, alpha 1-AT and TF were increased in periodontitis sites over
      gingivitis sites, although these differences were not statistically significant
      (p greater than 0.1). When the results were expressed on a concentration basis,
      alpha 2-M levels from diseased sites were significantly higher than healthy sites
      (p less than 0.01). In addition, GCF TF concentration was increased in
      periodontitis compared to healthy sites (p = 0.03).

PMID- 1376334
TI  - Parvalbumin-containing nonpyramidal neurons in intracortical transplants of rat
      hippocampal and neocortical tissue: a light and electron microscopic
      immunocytochemical study.
AB  - Previous immunocytochemical studies have shown that GABAergic nonpyramidal
      neurons of the rat hippocampus survive in intracerebral transplants. However,
      information is still lacking about the dendritic organization and the input
      synapses of these cells as well as their capacity to express the calcium-binding
      protein parvalbumin (PARV) under transplant conditions. In the present study, a
      monoclonal antibody against PARV was used to examine the dendritic morphology and
      the synaptic organization of parvalbumin-containing GABAergic neurons in
      hippocampal and dentate transplants. In addition, parvalbumin-containing
      nonpyramidal neurons were studied in neocortical transplants to compare the
      differentiation of grafted allocortical and neocortical nonpyramidal neurons.
      Tissue blocks of hippocampus and fascia dentata and of the parietal neocortex
      were taken from late embryonic rats (E 21 and E 16, respectively) and were
      transplanted into a cavity in the somatosensory cortex of young adult rats. After
      3.5 or 7 months survival, the recipient brains were fixed by perfusion and
      immunostained for PARV. As in the hippocampal formation in situ, PARV-containing
      neurons in the hippocampal transplants were observed within and in the vicinity
      of the pyramidal and granule cell layer. In neocortical transplants, PARV
      immunoreactive cells were distributed in all parts of the transplant with
      dendrites extending in various directions. In both hippocampal and neocortical
      transplants, immunoreactive dendrites were smooth and displayed the
      characteristic regular varicosities known from in situ studies of these cells.
      Numerous unlabeled terminals as well as a few immunoreactive boutons established
      synapses on the immunoreactive dendrites. PARV-positive terminals formed the
      typical pericellular baskets around the immunonegative cell bodies of pyramidal
      neurons and granule cells in the transplants. They established symmetric synapses
      with cell bodies and proximal dendrites. Synapses on axon initial segments were
      absent or rare. Our results demonstrate that allocortical as well as neocortical
      nonpyramidal neurons transplanted to the neocortex of adult recipients survive
      transplantation, express the calcium-binding protein parvalbumin, and develop a
      cell-specific morphology.

PMID- 1376336
TI  - Problems with paradigms in a caring profession.
AB  - The terms 'paradigms' and 'paradigm shifts' entered everyday language following
      the publication in 1962 of Kuhn's book The Structure of Scientific Revolutions.
      Kuhn's original usage of these terms in relation to 'normal' science has since
      been inappropriately applied to other areas of formal knowledge. Their use in
      relation to nursing is conceptually flawed, and is an unnecessary distraction
      from the more modest, but nevertheless rigorous, approaches to the elucidation
      and generation of knowledge for practice which are required.

PMID- 1376335
TI  - Intrinsic and commissural connections of the rat inferior colliculus.
AB  - This study analyzes the distribution of the intrinsic and commissural fiber
      plexuses originating in the central nucleus of the inferior colliculus in the
      rat. The anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) was
      injected iontophoretically at different places along the tonotopic axis of the
      central nucleus and visualized immunohistochemically. In coronal sections the
      terminal fields of axons originating at each injection site are seen to create
      four well-defined bands across the rostrocaudal extent of the inferior
      colliculus, two in the ipsilateral and two in the contralateral side. The
      "ipsilateral main band" extends dorsomedially and ventrolaterally from the
      injection site, in register with the known isofrequency contours of the central
      nucleus, spanning this nucleus and extending into the dorsal cortex of the
      inferior colliculus. The "ipsilateral external band" is located in the external
      cortex, where it is oriented dorsoventrally, slightly oblique to the pial
      surface. In caudal sections, the ventral portion of these two bands appear to
      join. The two bands in the contralateral inferior colliculus occupy a symmetric
      position to those of the ipsilateral side, forming a mirror-like image. The
      position of the four bands changes as the position of the injection site is
      varied along the frequency gradient axis of the central nucleus. After
      ventromedial (high frequency area) injections, the main band is ventral and
      medial, and the external band ventral and lateral. After more dorsolateral (lower
      frequency) injections, the main band is more dorsal and lateral, whereas the
      external band is more dorsal but more medial. Thus, the change in the position of
      the external band is separate and opposite to that of the main band. We suggest
      that the main bands represent isofrequency contours. Since the projection from
      the central nucleus to the external cortex of the inferior colliculus also
      appears to be tonotopic, we also propose a tonotopic organization for the
      external cortex. The main bands overlap the terminal field of the lemniscal
      fibers in the central nucleus; thus, it is concluded that the intracollicular
      fibers contribute to the formation of the known fibrodendritic laminae of the
      central nucleus. A possible role in preservation of frequency information and
      integration of other different acoustic parameters is proposed for the main
      bands. The external bands could participate in polysensory integration, and the
      commissural connections could be involved in hitherto unknown stages of binaural
      processing of sound. Based on our results, several modifications are proposed for
      delineating the subdivisions of the inferior colliculus.

PMID- 1376337
TI  - In the eye of the beholder: pretesting the effectiveness of health education
      materials.
AB  - Health educators at the University of Massachusetts evaluated five posters to
      determine whether students comprehended, identified with, and were motivated by
      the messages, which dealt with aspects of safer sex, alcohol use, and stress
      management. Pretesting, they suggest, provides an opportunity for remedying
      design flaws before distributing materials, improving effectiveness, and saving
      money by assuring that the target audience receives the intended message. Six
      suggestions for improving effectiveness and acceptability of printed health
      education materials are offered.

PMID- 1376338
TI  - Sulfated glycans directly interact with mouse Thy-1 and negatively regulate Thy-1
      mediated adhesion of thymocytes to thymic epithelial cells.
AB  - Thy-1 is a major brain cell surface glycoprotein of adult mammal species also
      expressed in rodent thymus. Despite extensive studies, the function(s) of this
      molecule has remained so far ill defined. We have recently shown that Thy-1 was
      involved in the adhesion of mouse thymocytes to thymic epithelium through a
      specific interaction with a heterophilic ligand(s) expressed on the epithelial
      cell surface. In the present study, we aimed at evaluating the interaction of
      sulfated glycans with mouse Thy-1, as well as its consequence on Thy-1-mediated
      thymic lympho-epithelial cell interaction. It was shown that 125I-labeled Thy-1
      directly bound to immobilized heparin. Sulfated glycans such as pentosan sulfate,
      dextran sulfate, and fucoidan were found to strongly inhibit the binding of Thy-1
      to heparin. In contrast, chondroitin sulfate, keratan sulfate, and heparan
      sulfate were not inhibitory. Sulfated glycans (e.g., pentosan sulfate, assayed at
      a concentration of 50 micrograms/ml) completely blocked the Thy-1-dependent
      adhesion of T cells to a mouse thymic epithelial cell monolayer. To explore the
      mechanism of this inhibition, we compared the ability of T cell to adhere to
      mouse thymic epithelial cell monolayer or to sulfated glycans. Our results
      suggest that sulfated glycans bind to a Thy-1 site distinct from that with which
      this molecule interacts with its heterophilic ligand. Moreover, sulfate glycans
      could modulate the binding of rat mAb directed at spatially distinct Thy-1
      epitopes. The present results identified a potential mechanism regulating Thy-1
      mediated lympho-epithelial cell adhesion.

PMID- 1376339
TI  - HIV induces IL-6 production by human B lymphocytes. Role of IL-4.
AB  - In vitro, normal B cells can produce TNF-alpha and IL-6 when activated with a
      first signal, and cytokines and B lymphocytes from some HIV-infected individuals
      spontaneously secrete TNF-alpha and IL-6, although the direct involvement of HIV
      has not been fully explored. In this study, we examined the effects of HIV
      (purified virus and a recombinant envelope protein) and various IL on TNF-alpha
      and IL-6 in vitro production by highly purified normal B cells. HIV alone did not
      induce IL-6 or TNF-alpha production by B cells from healthy subjects. HIV induced
      IL-6 production (500 to 1500 pg) in the presence of IL-4, with a slight
      production of TNF-alpha. IL-6 production occurred independently of the presence
      or absence of TNF-alpha in contrast with Staphylococcus aureus cowan + IL-2
      activated B cells. Other IL, particularly IL-2, were unable to induce IL-6
      secretion by HIV-activated B cells. In vivo-activated B cells from HIV-infected
      patients spontaneously produce moderate quantities of IL-6 and TNF-alpha. This
      secretion was markedly increased by HIV, suggesting that IL-6-secreting B cells
      contain anti-HIV antibody-producing B cells. However, contrary to normal B cells,
      IL-6 production by B cells from HIV-infected patients was not further enhanced by
      IL-4. Then HIV itself is able to induce an autocrine production of IL-6 upon
      interaction with IL-4, which can contribute to the hypergammaglobulinemia and to
      the global B cell dysfunction observed in HIV-infected patients.

PMID- 1376340
TI  - Prevention and therapy of experimental autoimmune neuritis by an antibody against
      T cell receptors-alpha/beta.
AB  - The mAb R73 directed to the TCR-alpha/beta of rat lymphocytes was tested for its
      therapeutic potential during the effector phase of experimental autoimmune
      neuritis (EAN) in Lewis rats. EAN can be actively induced by immunization with
      bovine peripheral nerve myelin, bovine P2 protein, or a peptide containing its
      neuritogenic epitope and serves as a model of the human Guilain-Barre syndrome.
      Adoptive transfer of activated P2-specific T lymphocytes also produces the
      monophasic disease (AT-EAN) characterized by inflammation and demyelination of
      peripheral nerves and highlights the central role of T lymphocytes in the
      pathogenesis of EAN. A single administration of the mAb R73 immediately after
      injection of activated P2-specific T line cells completely prevented the
      development of clinical and electrophysiologic signs of EAN in most animals and
      greatly alleviated the disease in the others. In further experiments mAb R73 was
      applied after the appearance of first clinical signs of EAN actively induced by
      immunization with a neuritogenic peptide or bovine peripheral nerve myelin. In
      both cases the anti-TCR-alpha/beta mAb reversed clinical signs of EAN and
      prevented the development of peripheral nerve dysfunction. In vivo and in vitro
      data suggest that impairment of Ag recognition and T cell function by occupancy
      of the TCR and R73-induced TCR-modulation rather than depletion of TCR-alpha/beta
      bearing lymphocytes is the decisive mechanism underlying suppression of EAN that
      is apparent already within 48 h of the first R73 injection.

PMID- 1376341
TI  - Experimental allergic encephalomyelitis mediated by cloned T cells specific for a
      synthetic peptide of myelin proteolipid protein. Fine specificity and T cell
      receptor V beta usage.
AB  - Proteolipid protein (PLP) is the major protein of central nervous system myelin.
      SJL (H-2s) mice immunized with a synthetic peptide corresponding to PLP residues
      139-151 develop acute EAE. In this study, 6 IAs-restricted, CD4+, TCR alpha beta
      bearing T cell clones were derived from SJL/J mice after immunization with this
      synthetic peptide. The clones responded in in vitro proliferative assays to the
      whole PLP molecule and to PLP peptide 139-151, but not to irrelevant Ag. They
      also responded to truncated and overlapping forms of the peptide but five
      distinct reactivity patterns were observed using these peptides. A panel of anti
      TCR V beta mAb and TCR V beta-specific cDNA probes were used to determine the TCR
      V beta usage of the clones. Five clones were found to use four different V beta
      (V beta 2, V beta 6, V beta 10, or V beta 17a), whereas the V beta on the sixth
      clone could not be identified. Five of the clones induced EAE of varying severity
      upon adoptive transfer into naive syngeneic mice or mice pretreated with
      irradiation and pertussis and one clone was nonencephalitogenic. The Ag-specific
      proliferative response of all but the nonencephalitogenic clone could be blocked
      by an anti-CD4 mAb. Thus, the clones showed differences in their fine specifity,
      TCR V beta usage, sensitivity to antibody blocking, and encephalitogenic potency.
      These data demonstrate that the T cell response to the encephalitogenic PLP
      peptide 139-151 is heterogeneous.

PMID- 1376342
TI  - Differences in activation of normal and glycosylphosphatidylinositol-negative
      lymphocytes derived from patients with paroxysmal nocturnal hemoglobinuria.
AB  - In these studies, the role of glycosylphosphatidylinositol (GPI)-anchored surface
      molecules during T cell activation was investigated in fresh T cells and T cell
      lines obtained from patients with paroxysmal nocturnal hemoglobinuria. For
      control, GPI-expressing T cells of the same patients were used. Unstimulated GPI-
      T cells exhibited significantly reduced surface expression of the activation Ag
      CD45R0, compared with GPI+ T cells. In addition, in measurements of
      proliferation, IFN-gamma production, and induction of second messengers such as
      cytoplasmic Ca2+, CD48- lymphocytes showed a similar response to TCR-specific
      stimulation, compared with CD48+ lymphocytes. In contrast, stimulation with the
      lectin PHA produced a decreased response of CD48- lymphocytes in these functions.
      In addition, stimulation with cross-linked CD59 mAb increased the proliferation
      of GPI-molecule expressing CD48+ T cell lines only. From these data, it can be
      concluded that GPI-anchored surface molecules play an important role in T
      lymphocyte activation.

PMID- 1376343
TI  - A monoclonal anti-idiotype specific for human polyclonal IgM rheumatoid factor.
AB  - One of the hallmarks of rheumatoid arthritis (RA) is the production of high
      titers of rheumatoid factor (RF) antibody directed against the Fc portion of IgG.
      Anti-Id that recognize the majority of monoclonal RF from patients with B cell
      dyscrasias are reactive with only 1 to 2% of these polyclonal RF from RA
      patients. We describe a new monoclonal anti-Id, 4C9, that recognizes a L chain
      determinant on polyclonal IgM RF from patients with RA but does not recognize a
      panel of monoclonal RF from patients with B cell malignancies. 4C9 reactivity is
      found in the serum of 34/43 RF-positive RA patients and in 12/12 RF-positive
      synovial fluids, but in only 1/14 RF-negative sera from RA patients and 1/22 sera
      containing monoclonal IgM RF. 4C9 reactivity is highly enriched in purified IgM
      RF from nine RA patients and represents a variable percentage of total IgM RF up
      to a maximum of 23%. Furthermore, 4C9 reactivity is enriched in the synovial
      fluid of three of five RA patients compared with serum, suggesting that 4C9
      reactive IgM RF are synthesized within the joint. IgG RF from RA synovial fluids
      are not 4C9 reactive, indicating either that different genes are used to encode
      IgM and IgG RF in RA patients, or that IgG RF have somatically mutated away from
      idiotypic reactivity.

PMID- 1376344
TI  - Membrane IgM-mediated signaling of human B cells. Effect of increased ligand
      binding site valency on the affinity and concentration requirements for inducing
      diverse stages of activation.
AB  - The potential for ligand-initiated signal transduction through B cell membrane
      IgM is assessed in terms of ligand concentration, binding site valency, and
      binding site affinity for membrane Ig. Estimates of the physicochemical
      requirements for achieving G0* enhancement of class II MHC expression, G1 entry,
      and S phase entry in human B cells were made by comparing the stimulatory effects
      of three affinity-diverse anti-Cmu2 mAb when in bivalent (unconjugated) form, or
      as mAb-dextran conjugates with low binding site valency (oligovalent ligands) or
      high binding site valency (multivalent ligands). An increase in binding site
      number (and concomitant molecular mass) caused a profound reduction in both the
      minimal concentration and affinity requisites for B cell activation. The
      enhancing effect of increased binding site valency was most evident for the
      signaling of those most distal stages in B cell activation, i.e., G1 and S phase,
      which were difficult to induce with bivalent ligands. The results suggest that
      highly multimeric TI-2 Ag may be good immunogens because they are able to elicit
      a full activation response not only from infrequent high affinity B cells, but
      also from a substantial proportion of the many lower affinity Ag-specific B cells
      in virgin B cell populations. Interestingly, the activation of B cells by ligands
      with binding sites of high intrinsic affinity (Ka = 5 x 10(8) M-1) was less
      influenced by increases in binding site valency than was B cell activation by
      ligands with intermediate binding site affinity (Ka = 2 x 10(7) M-1). This
      suggests that the minimal epitope valency requirement for T cell-independent B
      cell activation by mIg cross-linking Ag may be dependent on the intrinsic
      affinity with which membrane Ig molecules on a given B cell interact with the
      redundantly expressed epitopes.

PMID- 1376345
TI  - Anti-human IgG causes basophil histamine release by acting on IgG-IgE complexes
      bound to IgE receptors.
AB  - We have reexamined the ability of anti-human IgG antibodies to induce histamine
      release from human basophils. A panel of purified murine mAbs with International
      Union of Immunological Societies-documented specificity for each of the four
      subclasses of human IgG was used. Of the 24 allergic subjects studied, the
      basophils of 75% (18/24) released greater than 10% histamine to one or more anti
      IgG1-4 mAb, whereas none of the 13 nonatopic donor's basophils released histamine
      after stimulation with optimal amounts of anti-IgG mAb. The basophils of 85%
      (11/13) of the nonatopic donors did respond to anti-IgE challenge, as did 92%
      (22/24) of the atopic donor cells. Histamine release was induced most frequently
      by anti-IgG3, and 10/18 anti-IgG responder cells released histamine with mAb
      specific for two or more different subclass specificities. The rank order for
      induction of histamine release was anti-IgG3 greater than anti-IgG2 greater than
      IgG1 greater than anti-IgG4. As in our previous study using polyclonal anti-IgG,
      100- to 300-micrograms/ml quantities of the anti-IgG mAb were required for
      maximal histamine release, about 1000-fold higher than those for comparable
      release with anti-human IgE. Specificity studies using both immunoassays and
      inhibition studies with IgE myeloma protein indicated that anti-IgG induced
      histamine release was not caused by cross-reactivity with IgE. Ig receptors were
      opened by lactic acid treatment so that the cells could be passively sensitized.
      Neither IgE myeloma nor IgG myeloma (up to 15 mg/ml) proteins could restore the
      response to anti-IgG mAb. However, sera from individuals with leukocytes that
      released histamine upon challenge with anti-IgG mAb could passively sensitize
      acid-treated leukocytes from both anti-IgG responder and nonresponder donors for
      an anti-IgG response. The only anti-IgG mAb that induced release from these
      passively sensitized cells were those to which the serum donor was responsive.
      Sera from non-IgG responders could not restore an anti-IgG response. These data
      led to the hypothesis that the IgG specific mAb were binding to IgG-IgE complexes
      that were attached to the basophil through IgE bound to the IgE receptor. This
      was shown to be correct because passive sensitization to anti-IgG could be
      blocked by previous exposure of the basophils to IgE. We conclude that anti-IgG
      induced release occurs as a result of binding to IgG anti-IgE antibodies and
      cross-linking of the IgE receptors on basophils.

PMID- 1376346
TI  - A universal T cell epitope-containing peptide from hepatitis B surface antigen
      can enhance antibody specific for HIV gp120.
AB  - Peptide-based vaccines that directly target T cell or B cell epitopes may have
      significant advantages over conventional vaccines. Further, synthetic chimeric
      peptides that combine strong T cell epitopes with poorly immunogenic, but
      immunodominant, B cell epitopes or strain-conserved B cell epitopes may be useful
      in eliciting antibody to such important regions. Here we characterize a human T
      cell epitope analyzed in 54 individuals immunized with a hepatitis B virus
      surface Ag vaccine. Primary cultures from a total of 59 immunized donors were
      assessed for their ability to respond to hepatitis B virus surface Ag and
      peptides, and five were non-responders (8.5%). T cell lines were established from
      the remaining 54 responders. Of the responders, it was found that the peptide
      representing amino acids 19 through 33 (19-33) elicited significant proliferation
      in lines derived from 50 donors. This "universal" T cell epitope, which was
      recognized in donors of many different HLA-DR and -DQ haplotypes, was then used
      to construct a chimeric peptide containing 19-33 and the third V region loop
      structure (V3 loop) of HIV-1 envelope gp 120, in an attempt to augment the immune
      response to the V3 loop peptide. The V3 loop is the region to which significant
      neutralizing antibody is directed. Thus, a strong immune response to a synthetic
      peptide that contains the strain-conserved V3 loop region could have significant
      therapeutic implications. The V3 loop/19-33 peptide was then used to prime mice,
      to determine whether V3 loop-specific antibody could be induced. The peptide
      elicited potent 19-33-specific proliferation in T cells isolated from draining
      lymph nodes, and in six of six mice anti-V3 loop antibody was elicited. Further,
      V3 loop/19-33-primed animals made significant levels of antibody that bound
      rgp120. These data suggest that, when a major T cell epitope is synthesized in
      tandem with the V3 loop, a significant immune response against the loop can be
      elicited. Thus, given the finding that neutralizing antibody may play a role in
      the control and/or prevention of HIV infection, an HIV vaccine composed of a T
      cell epitope-containing peptide may prove effective. In addition, this type of
      approach can be generalized to the design of peptide-based vaccines.

PMID- 1376347
TI  - Human recognition of T cell epitopes on the Plasmodium vivax circumsporozoite
      protein.
AB  - In order to identify T cell epitopes recognized by human in the Plasmodium vivax
      circumsporozoite protein, 28 overlapping synthetic peptides spanning the entire
      circumsporozoite protein were tested for their ability to stimulate proliferation
      of PBMC from 22 adults living in a malaria-endemic area of the Colombian Pacific
      Coast and from four individuals who never had a history of malaria infection. In
      addition, BALB/c mice were immunized with pools of peptides, and their lymph node
      cells were stimulated in vitro with individual peptides. Four epitopes were
      recognized by human lymphocytes but not all of them by mice. One of the epitopes
      was located inside the central repetitive B cell immunodominant domain. Several
      of the variants of the repeats were recognized by about one-third of the studied
      individuals. Another T cell epitope was located in the amino terminus and the
      other two in the carboxyl region. Peptides were recognized by both immune and
      nonimmune donors. Some of them were frequently recognized suggesting a lack of
      genetic restriction, whereas some others were recognized by only a few
      individuals but induced strong proliferation. These epitopes may be of potential
      value for a malaria subunit vaccine.

PMID- 1376348
TI  - A synthetic peptide spontaneously self-assembles to reconstruct a group-specific,
      conformational determinant of hepatitis B surface antigen.
AB  - A cysteine-rich peptide of sequence 124 to 147 of the major protein of hepatitis
      B surface Ag (HBsAg) was synthesized. On cleavage and subsequent work-up it was
      found that all of the cysteine sulfhydryl groups had spontaneously formed
      disulfide bonds to yield a heterogenous mixture of multiple forms with molecular
      masses ranging from 8 to 35 kDa (peptide OS[124-147]). In a direct ELISA peptide
      OS[124-147] showed a high degree of cross-reactivity with polyclonal anti-HBsAg
      antiserum whereas the HBsAg-related antigenicity of its disulfide-reduced analogs
      was insignificant. Peptide OS[124-147] was also recognized by all 15 of the anti
      HBsAg-positive human sera tested. Further studies revealed that peptide OS[124
      147] represents the conformational, disulfide-dependent "a" determinant of HBsAg
      and elicits antibodies that cross-react with a variety of HBsAg subtypes. Anti
      peptide antibodies bound to the corresponding native epitope with an apparent
      affinity higher than that of homologous antisera. Finally, polyclonal anti-OS[124
      147] antibodies could also immunoprecipitate purified Dane particles in solution.
      Together these studies indicate that peptide OS[124-147] represents an excellent
      candidate component of a peptide-based vaccine for hepatitis B.

PMID- 1376349
TI  - Unique palindromic sequences in synthetic oligonucleotides are required to induce
      IFN [correction of INF] and augment IFN-mediated [correction of INF] natural
      killer activity.
AB  - Thirty-mer single-stranded oligonucleotides, with a sequence chosen from the
      known cDNA encoding the 64-kDa protein named Ag A or the MPB-70 protein of
      Mycobacterium bovis BCG and the human cellular proteins such as complement
      component 1 inhibitor and Ig rearranged lambda-chain, were used to dissect the
      capability to induce IFN and to augment NK cell activity of mouse spleen cells by
      coincubation in vitro. Three with the hexamer palindromic sequence as GACGTC were
      active, whereas two kinds of oligonucleotides with no palindrome were inactive.
      The oligonucleotides containing at least one of the different palindromic
      sequences showed no activity. When a portion of the sequence of the inactive
      oligonucleotides was substituted with either palindromic sequence of GACGTC,
      AGCGCT, or AACGTT, the oligonucleotide acquired the ability to augment NK
      activity. In contrast, the oligonucleotides substituted with another palindromic
      sequence such as ACCGGT was without effect. Furthermore, exchange of two
      neighboring mononucleotides within, but not outside, the active palindromic
      sequence destroyed the ability of the oligonucleotides to augment NK cell
      activity. Stimulation of spleen cells with the substituted oligonucleotide, A4a
      AAC, induced production of significant amounts of IFN-alpha/beta and small
      amounts of IFN-gamma. Augmentation of NK activity of the cells by the
      oligonucleotide was ascribed to IFN-alpha/beta production. These results strongly
      suggest that the presence of the unique palindromic sequences, such as GACGTC,
      AGCGCT, and AACGTT, but not ACCGGT, is essential for the immunostimulatory
      activity of oligonucleotides.

PMID- 1376350
TI  - Surface markers, heavy chain sequences and B cell lineages.
AB  - A unifying theory of B cell development and lineage commitment is presented.
      There are two firmly established B lineages: cells which normally arise only from
      fetal sources and lack N insertions in their rearranged heavy chains; and N
      containing cells which arise from adult bone marrow precursors (and perhaps from
      late fetal sources). Commitment to the expression of CD5 and the capacity for
      long-life (or self-renewal) are induced as a consequence of sIg cross-linking,
      typically by a repeating epitope, thymus independent type two antigen.
      Alternatively, activation resulting from cognate interaction with a helper T cell
      does not induce CD5 but results in lower expression of J11d. In this case
      activation occurs in the absence of sIg cross-linking. It is further proposed
      that differences in the Ig repertoire make it highly likely that fetal/neonatal,
      but not adult derived B cells will be induced to express CD5. The model offers a
      plausible explanation for the correlation of CD5 expression and natural
      autoantibody production by neonatal B cells. Possible sources of pathogenic
      autoantibody are discussed in the context of this model.

PMID- 1376351
TI  - Development and function of the early B cell repertoire.
AB  - The early B cell repertoire is characterized by extensive interconnectivity,
      autoreactivity and multispecificity. Our preliminary sequence analysis of some of
      the idiotype specific antibodies is beginning to provide molecular clues to
      explain the observed multireactivity and the expression of shared idiotypic
      determinants on immunoglobulins of early B cells. The VH gene rearrangements
      analyzed are typical of the early pre-B cell and CD5 B cell repertoire. Some of
      these include shared or identical CDR3 regions resulting from the use of germline
      VH, D and JH gene segments in the absence of N region addition. As previously
      described, the most D proximal VH genes are also used most frequently.
      Collectively these genetic restrictions, together with the lack of somatic
      mutation, suggest that the characteristic self reactivity of the early B cell
      repertoire is related to the expression of germline gene segments and limited use
      of diversification mechanisms. It has also been possible for the first time to
      isolate hybridomas secreting functional IgM molecules which use the most D
      proximal VH gene, VH81X. These antibodies and another example from the VH7183
      family have a broad multireactivity pattern possibly because of the presence of
      an unusually high number of charged amino acid groups present in the VH region.
      These findings are preliminary and more extensive studies are needed to establish
      if these groups are responsible for the highly cross-reactive nature of these
      antibodies. Nevertheless, these unusual characteristics signify a unique role for
      antibodies expressing this VH gene during B cell development. It is also clear
      that the observed anti-lymphocyte reactivity, another feature of the newborn
      repertoire, is the result of the prevalence of B cells using similar if not
      identical VHDJH genes and DJH joins. The development of these B cells appears to
      occur consistently in early ontogeny and, again, are not found in conventional
      splenic B cells obtained from the normal adult. Understanding the functional
      significance of the early appearance of these antibodies may help to clarify and
      understand their role during development as well as in autoimmunity. We propose
      that the unique self reactive nature of the early repertoire provides a pattern
      within which self-assertiveness develops and results in the establishment of the
      adult repertoire. In doing so, dominant clones are established which may or may
      not be within, but whose selection and differentiation is directed by the CD5 B
      cell subset.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1376352
TI  - Mycobacterial infection primes T cells and macrophages for enhanced recruitment
      of neutrophils.
AB  - C57BL/6 mice intraperitoneally infected with Mycobacterium bovis BCG (substrain
      Pasteur) recruited significantly higher numbers of neutrophils after an
      intraperitoneal inoculation of either BCG protein antigen or of endotoxin than
      uninfected control mice. Antigen-induced neutrophil recruitment was mediated by T
      cells of both CD4+ and CD8+ phenotype and was also observed in the C5-deficient
      DBA/2 mouse strain. The adoptive transfer of immune serum did not prime mice for
      enhanced antigen-mediated recruitment of neutrophils. The endotoxin-mediated
      recruitment of neutrophils was also enhanced in infected as compared to
      uninfected DBA/2 mice. Finally, endotoxin-pulsed purified macrophages from
      infected C57BL/6 mice recruited higher numbers of neutrophils than endotoxin
      pulsed macrophages from normal mice in an adoptive transfer to peritoneal
      cavities of naive recipient mice. These data show that during mycobacterial
      infection, T cells and macrophages are primed for recruitment of neutrophils
      after being triggered in specific or nonspecific ways. This may represent a means
      to cope with secondary infections by allowing for extensive neutrophil
      infiltration readily upon microbial challenge.

PMID- 1376353
TI  - Detection and analysis of the 80-kd lipopolysaccharide receptor in macrophages
      derived from Lpsn and Lpsd mice.
AB  - An 80-kd lipopolysaccharide (LPS)-binding protein with specificity for the lipid
      A region has been identified on lymphocyte and macrophage membranes. In an
      attempt to gain insight into the hyporesponsiveness of C3H/HeJ (Lpsd) mice to
      LPS, an affinity-purified rabbit polyclonal IgG with specificity for this
      receptor was used to compare the expression and distribution of the 80-kd LPS
      receptor on thioglycollate-elicited peritoneal macrophages derived from normal
      (Lpsn) and (Lpsd) mice. By enzyme-linked immunosorbent assay, immunofluorescence
      microscopy, and flow cytometry, macrophages from Lpsn and Lpsd mice showed
      comparable expression of the 80-kd LPS receptor, although only a subpopulation of
      macrophages from both strains express it. Macrophages from both strains showed
      indistinguishable surface distribution of the 80-kd LPS receptor, as determined
      by confocal microscopy and analysis using an anchored cell analysis station.
      Treatment of macrophages with interferons, protein-rich LPS, or glucocorticoids,
      agents known to modulate a variety of macrophage cell surface markers and
      receptors, failed to alter expression of the 80-kd receptor. These findings
      support the hypothesis that the hyporesponsiveness of the Lpsd mouse strains to
      LPS is not due to an absence of receptors but rather is distal to binding of LPS
      and most likely attributable to a failure of these macrophages to transduce the
      signal derived at the cell surface to the interior of the cell.

PMID- 1376355
TI  - F4/80 monoclonal antibody.

PMID- 1376354
TI  - Characterization and use of monoclonal and polyclonal antibodies against the
      mouse interferon-gamma receptor.
AB  - To facilitate investigation of its physical and functional properties, 11
      monoclonal antibodies (mAbs) and a goat polyclonal IgG specific for the mouse
      interferon- (IFN-gamma) receptor were characterized and their potential uses
      studied. Eight of the mAbs interacted with epitopes on the extracellular domain
      of the receptor, two interacted with epitopes on the intracellular domain, and
      one interacted with an epitope that could not be localized definitively to either
      region. Of the 11 mAbs, the majority (8) were IgGs, 2 were IgMs, and 1 was an
      IgA. Relative avidities of the seven that could be determined ranged from 333 to
      0.002 microM-1. Both the polyclonal goat IgG and mAb GR-20 (the latter specific
      for an epitope in the binding site for IFN-gamma) blocked binding of the ligand
      and, as expected, prevented induction by IFN-gamma of priming of macrophages for
      tumor cell killing. None of the other mAbs had an effect despite the fact that GR
      22 partially (greater than 50%) blocked binding of IFN-gamma. Neither the
      polyclonal IgG nor any of the mAbs had an agonist effect. The relative usefulness
      of the antibodies for immunoprecipitation, immunoblotting, immunoassay, and cell
      staining with and without prior fixation is described. The results of
      immunocytochemical staining directly confirmed that the majority of
      immunologically reactive receptor protein expressed by cells is intracellular. To
      facilitate use by other investigators, the hybridomas that produce these mAbs
      will be offered to the American Type Culture Collection.

PMID- 1376356
TI  - [Immunohistological investigation of epithelial components of adenolymphoma of
      the parotid gland].
AB  - In order to develop a more objective method of evaluating the origin of
      adenolymphoma, we immunohistochemically investigated the expression of
      cytokeratins, vimentin, S-100 protein, and alpha-smooth-muscle actin using the
      avidin-biotin-peroxidase (ABC) method in ethanol-fixed paraffin-embedded
      specimens from 8 adenolymphomas. Several kinds of monoclonal antibodies which
      react monospecifically with each subclass of cytokeratins were used. Results were
      compared with specimens of 8 normal parotid glands by radical neck dissection in
      patients with other diseases who had not undergone radiotherapy. In the
      adenolymphoma specimens, basal cells were strongly positive for CK-6, but
      reactivity of columnar cells was apparently reduced. In contrast, columnar cells
      were strongly positive for CK-7, but reactivity of basal cells was reduced. In
      normal parotid gland specimens, CK-7 was also detected in all columnar cells in
      the ductal system, although some duct cells around the columnar cells, which
      showed strong CK-6 expression, showed poor CK-7 expression. alpha-smooth-muscle
      actin was present in myoepithelial cells in normal parotid gland specimens, but
      not in basal cells of adenolymphoma or of the normal ductal system, which were CK
      6-positive. As these characteristic findings were consistently observed in all
      specimens, the demonstration of CK-6, CK-7, and alpha-smooth-muscle actin may be
      useful in the recognition and classification of columnar and basal cells. CK-8
      was present in both columnar and basal cells of adenolymphoma and of the normal
      duct, but in the normal parotid gland, acinus cells were also strongly positive
      for CK-8.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376357
TI  - Substance P produces sodium and bicarbonate secretion in porcine jejunal mucosa
      through an action on enteric neurons.
AB  - The neuropeptide substance P (SP) produces transient elevations in short-circuit
      current (Isc), a measure of active ion transport, across sheets of small
      intestinal mucosae from several animal species, but the ionic basis of this
      action remains unknown. The aim of this study was to test the hypothesis that SP
      promotes electrogenic anion secretion in the porcine proximal jejunum, an
      intestinal segment analogous to the human upper small intestine. Sheets of
      jejunal mucosa with attached submucosa responded to serosal (S), but not luminal
      (L) addition of 0.1 microM SP with a transient increase in Isc that was reduced
      in tissues pretreated with the Na(+)-K(+)-Cl- cotransport inhibitor bumetanide
      (10 microM) or bathed in media lacking Cl- or HCO3- ions. SP produced biphasic
      effects on transepithelial Na+ and Cl- fluxes; it initially stimulated a L
      directed Na+ secretory flux during a 5-min period in which peptide-induced Isc
      elevations were maximum. The return of the Isc to base-line levels was temporally
      associated with an increase in L-directed Cl- transport. Both effects of SP were
      absent in tissues either pretreated with the neuronal conduction blocker
      tetrodotoxin (0.1 microM) or bathed in HCO3(-)-deficient media. Bumetanide
      abolished the Na+ secretory actions of SP, but did not affect peptide-induced Cl-
      secretion. pH-Stat titration experiments revealed that mucosal sheets alkalinized
      the L bathing medium at a rate twice that of the S medium. SP simultaneously
      increased and suppressed L and S alkalinization, respectively; this effect
      presumably represents HCO3- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376358
TI  - Neurokinin receptors and mucosal ion transport in porcine jejunum.
AB  - Neurokinin (NK) peptides such as substance P (SP) may modulate epithelial ion
      transport in the small intestine. The present study was undertaken to examine the
      pharmacological mechanisms by which SP and its endogenous homologs NKA and NKB
      affect active electrolyte transport in the mucosa of porcine jejunum. Neurokinins
      and NK agonist analogs increased short circuit current, a measure of active ion
      transport, across sheets of jejunal mucosa-submucosa with the order of potency:
      SP greater than [beta-Ala8]NKA4-10 greater than or equal to [Sar9,Met(O2)11]SP
      greater than NKA = Arg-NKB greater than NKB after their addition to the serosal
      aspect of tissues (SP EC50 = 11 nM). Epithelial responses to SP or NKA underwent
      rapid autotachyphylaxis and unidirectional cross-tachyphylaxis after repeated
      peptide administration. The neuronal conduction blocker tetrodotoxin
      significantly reduced NK efficacy. SP activity was significantly reduced in
      tissues pretreated with the muscarinic cholinoceptor blocker atropine or the
      eicosanoid synthesis inhibitor eicosa-5,8,11,14-tetraynoic acid. NK peptides
      increased contractility in longitudinally oriented strips of jejunal smooth
      muscle with an order of potency: [Sar9,Met(O2)11]SP greater than SP greater than
      Arg-NKB = [beta-Ala8]NKA4-10 greater than or equal to NKB = NKA (SP EC50 = 11
      nM). SP-induced contractions were reduced by 70 to 80% in tissues pretreated with
      atropine or the neuronal Ca++ channel blocker, omega-conotoxin. [125I]Bolton
      Hunter-substance P (BHSP) bound specifically to a single population of sites in
      slide-mounted sections of mucosa-submucosa and smooth muscle with Kd = 0.3 and
      0.1 nM and Bmax = 18 and 31 fmol/mg protein, respectively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1376359
TI  - Dual effects of endothelins -1, -2 and -3 on guinea pig field-stimulated ileum:
      possible mediation by two receptors coupled to pertussis toxin-insensitive
      mechanisms.
AB  - This study compared the effects of endothelin-1 (ET-1), ET-2 and ET-3 on the
      guinea pig field-stimulated ileum. All ETs (0.3-30 nM) caused graded inhibitions
      of nerve-mediated responses followed by sustained contractions. The rank order of
      potencies for the twitch depressor effect (IC50S) was ET-3 = ET-1 greater than ET
      2, with ET-3 causing greater maximal inhibition than ET-1 or ET-2. The rank order
      of potencies for contraction (EC50S) was ET-1 = ET-2 greater than ET-3, with ET-1
      causing greater maximal contraction than ET-2 or ET-3. Twitch inhibition by ET-1
      (3 nM) was unaffected by indomethacin (5.6 microM), cromakalim (10 microM),
      glibenclamide (3 microM) or nicardipine (0.1 microM). ET-1-induced contraction
      was unaltered by tetrodotoxin (0.3 microM), atropine (0.3 microM) or
      glibenclamide, but was reduced by indomethacin. Cromakalim and nicardipine
      virtually abolished ET-1-induced contraction. ET-1 (up to 30 nM) did not
      potentiate submaximal contractions induced by acetylcholine, histamine,
      bradykinin or substance P. ET-3 relaxed ileal segments precontracted with either
      acetylcholine (0.3 microM) or histamine (1 microM). Pretreatment of guinea pigs
      with pertussis toxin (50 micrograms/kg i.p., 6 days beforehand) did not influence
      either effects of ET-1 on the field-stimulated ileum. Our data suggest that the
      dual effects of ETs on the guinea pig isolated ileum are mediated by distinct
      receptors and possibly involve different mechanisms of action. The transient
      inhibition of responses to field stimulation seems unrelated to activation of ATP
      sensitive potassium channels and is rather insensitive to L-type Ca++ channel
      blockade.

PMID- 1376360
TI  - Angiotensin II amplifies arterial contractile response to norepinephrine without
      increasing Ca++ influx: role of protein kinase C.
AB  - We investigated whether the enhanced contractile response to norepinephrine
      caused by a subthreshold concentration of angiotensin II was associated with an
      increased 45Ca++ influx or net uptake. Rabbit facial artery segments were mounted
      isometrically to measure the 45Ca++ influx and net uptake in response to
      norepinephrine. The contractile response to norepinephrine (3 microM) in the
      presence of angiotensin II (0.1 nM) was 149.5 +/- 7.4% of control. This response
      amplification was not associated with changes in norepinephrine-induced 45Ca++
      influx or net uptake. Angiotensin II also potentiated the contractile response to
      caffeine obtained in a Ca(++)-free buffer containing ethylene glycol bis(beta
      aminoethyl ether)N,N'-tetraacetic acid (2 mM) to 148.0 +/- 4.8% of control. In
      both cases, the amplification was prevented by pretreatment with either
      staurosporine (10 nM) or calphostin C (100 nM), two inhibitors of protein kinase
      C. We conclude that angiotensin II potentiation of norepinephrine-induced
      vascular tone occurs in the absence of changes in stimulated Ca++ entry. This
      potentiation may be due to an increase in intracellular sensitivity to Ca++,
      possibly mediated by protein kinase C.

PMID- 1376361
TI  - Rapamycin and FK506 differentially inhibit mast cell cytokine production and
      cytokine-induced proliferation and act as reciprocal antagonists.
AB  - We have previously demonstrated that cyclosporine (CSA) and FK506 are able to
      selectively inhibit cytokine production by murine mast cell lines at
      concentrations comparable to those observed with thymus-derived lymphocytes (T
      cells). The selectivity of these effects were demonstrated by the failure of CSA
      and FK506 to inhibit cytokine-induced mast cell proliferation at equivalent or
      higher concentrations. In this report, we examined the ability of rapamycin (RAP)
      to inhibit cytokine production and cytokine-induced proliferation by a factor
      dependent murine mast cell line and compared its activity to that of the
      structurally related macrolide FK506. The mast cell clone, MC/9, was stimulated
      to produce cytokines with phorbol myristate acetate plus the calcium ionophore
      A23187, or to proliferate in response to exogenous cytokines such as interleukin
      3 and interleukin-4, produced by the helper T cell clone D10.G4. RAP did not
      inhibit cytokine production by MC/9, even at concentrations greater than 1000 nM.
      FK506 and CSA inhibited cytokine production with IC50 of 0.8 and 16.2 nM,
      respectively. In contrast to its lack of effect on cytokine production, RAP
      potently inhibited cytokine-induced proliferation of MC/9 cells with an IC50 of
      1.9 nM. Because RAP and FK506 are structurally related and yet have divergent
      biological effects, we examined the ability of RAP to antagonize inhibitory
      effects of FK506 on mast cell cytokine production and the ability of FK506 to
      antagonize inhibitory effects of RAP on cytokine-induced mast cell proliferation.
      The addition of RAP in molar excess reversed inhibition of mast cell cytokine
      production mediated by FK506, but not that of CSA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1376362
TI  - Acute effects of buprenorphine, hydromorphone and naloxone in methadone
      maintained volunteers.
AB  - Buprenorphine is an opioid agonist-antagonist being evaluated for treatment of
      opioid dependence. This study characterized the effects of buprenorphine in
      comparison to naloxone, hydromorphone and saline, in methadone-dependent
      volunteers. In a residential laboratory, 6 volunteer male opioid abusers
      maintained on 30 mg of methadone daily underwent pharmacological challenges 2 to
      3 times per week. Pharmacological challenges consisted of a double-blind i.m.
      injection of: buprenorphine (dose range 0.5-8.0 mg), hydromorphone (5 and 10 mg),
      naloxone (0.1 and 0.2 mg) or saline. Injections were given 20 hr after the last
      dose of methadone. Measures included physiologic indices, and self-report and
      observer ratings of drug effects. Naloxone and hydromorphone produced
      characteristic antagonist-like and agonist-like effects, respectively, on
      subjective, observer and physiologic indices. None of the doses of buprenorphine
      were consistently or systematically identified as an opioid agonist or antagonist
      on any of the measures. Thus buprenorphine produced minimal effects in methadone
      dependent patients. The lack of agonist effects suggests buprenorphine has a low
      abuse potential in methadone-dependent patients. The lack of antagonist effects
      suggests buprenorphine can be administered safely to subjects dependent on a low
      dose of methadone. This lack of effect of buprenorphine distinguishes it from
      other mixed agonist antagonists previously tested, which produced antagonist
      effects in this procedure.

PMID- 1376363
TI  - Toluidine blue and Lugol's iodine application in the assessment of oral malignant
      disease and lesions at risk of malignancy.
AB  - The purpose of the study was to determine if toluidine blue application and
      counter staining with Logul's iodine would aid in diagnosis of oral dysplastic or
      malignant lesions. The sensitivity, specificity, and predictive values were
      studied. Routine use of these tissue stains was found to be sensitive and
      specific. The use of stains provided better demarcation of oral squamous cell
      carcinoma and dysplastic changes and assisted in site selection for diagnostic
      biopsy. The use of toluidine blue and Lugol's iodine can assist in assessment of
      patients at risk of developing malignant disease and those with lesions that are
      clinically suspect of dysplasia or malignancy.

PMID- 1376364
TI  - Mutant conformation of p53. Precise epitope mapping using a filamentous phage
      epitope library.
AB  - Many naturally occurring point mutations in the p53 gene lead to a proportion of
      the encoded protein molecules adopting a distinct, "mutant" conformation
      characterized by exposure of a normally cryptic epitope recognized by the
      monoclonal antibody PAb240. Here the PAb240 epitope is defined using a
      filamentous phage epitope library. The hexapeptides displayed by the PAb240
      binding phage isolated from the library were all highly related and allowed both
      direct localization of the epitope and prediction of a specific interaction
      between PAb240 and Xenopus TFIIIA. This study demonstrates for the first time the
      power of phage epitope libraries in the precise definition of previously unmapped
      epitopes. Identification of the PAb240 epitope precisely defines a region of the
      p53 molecule structurally altered by the mutation-induced conformational shift.

PMID- 1376365
TI  - Posttranslational side chain modification of a viral epitope results in
      diminished recognition by specific T cells.
AB  - A stretch of 16 amino acid residues within the nominal phosphoprotein of rabies
      virus was shown to carry an immunodominant epitope for class I- and class II
      restricted T cells. The nominal phosphoprotein of rabies virus is thought to be
      heterogeneously phosphorylated at multiple serine and threonine residues. The
      synthetic peptide that expressed the T-cell epitope contained a single serine
      residue corresponding to position 196 of the protein. Phosphorylation of this
      serine within the synthetic peptide caused a significant decrease of the
      antigenic potency of the peptide. A similar effect was seen if the serine was
      replaced by an alanine or if the peptide was glycosylated at its acidic residues.
      These data suggest that T-cell-mediated recognition of antigen presented by major
      histocompatibility complex class I- or II-positive cells is impaired not only by
      point mutations but also by posttranslational side chain modifications of
      residues within viral epitopes.

PMID- 1376366
TI  - Induction of cytotoxic T cells to a cross-reactive epitope in the hepatitis C
      virus nonstructural RNA polymerase-like protein.
AB  - Cytotoxic T lymphocytes (CTL) have been found to mediate protection in vivo
      against certain virus infections. CTL also may play an important role in control
      of infection by hepatitis C virus (HCV), but no CTL epitopes have yet been
      defined in any HCV protein. The nonstructural protein with homology to RNA
      polymerase should be a relatively conserved target protein for CTL. To
      investigate the epitope specificity of CTL specific for this protein, we used 28
      peptides from this sequence to study murine CTL. Mice were immunized with a
      recombinant vaccinia virus expressing the HCV nonstructural region corresponding
      to the flavivirus NS5 gene (RNA polymerase), and the primed spleen cells were
      restimulated in vitro with peptides. CTL from H-2d mice responded to a single 16
      residue synthetic peptide (HCV 2422 to 2437). This relatively conserved epitope
      was presented by H-2d class I major histocompatibility complex (MHC) molecules to
      conventional CD4- CD8+ CTL but was not recognized by CTL restricted by H-2b.
      Moreover, exon shuffle experiments using several transfectants expressing
      recombinant Dd/Ld and Kd demonstrated that this peptide is seen in association
      with alpha 1 and alpha 2 domains of the Dd class I MHC molecule. This peptide
      differs from the homologous segments of this nonstructural region from three
      other HCV isolates by one residue each. Variant peptides with single amino acid
      substitutions were made to test the effect of each residue on the ability to
      sensitize targets. Neither substitution affected recognition. Therefore, these
      conservative mutations affected peptide interaction neither with the Dd class I
      MHC molecule nor with the T-cell receptor. Because these CTL cross-react with all
      four sequenced isolates of HCV in the United States and Japan, if human CTL
      display similar cross-reactivity, this peptide may be valuable for studies of HCV
      diagnosis and vaccine development. Our study provides the first evidence that
      CD8+ CTL can recognize an epitope from the HCV sequence in association with a
      class I MHC molecule.

PMID- 1376368
TI  - Identification of envelope protein epitopes that are important in the attenuation
      process of wild-type yellow fever virus.
AB  - Monoclonal antibodies (MAbs) have been prepared against vaccine and wild-type
      strains of yellow fever (YF) virus, and envelope protein epitopes specific for
      vaccine (MAbs H5 and H6) and wild-type (MAbs S17, S18, S24, and S56) strains of
      YF virus have been identified. Wild-type YF virus FVV, Dakar 1279, and B4.1 were
      each given six passages in HeLa cells. FVV and B4.1 were attenuated for newborn
      mice following passage in HeLa cells, whereas Dakar 1279 was not. Examination of
      the envelope proteins of the viruses with 87 MAbs showed that attenuated viruses
      gained only the vaccine epitope recognized by MAb H5 and lost wild-type epitopes
      recognized by MAbs S17, S18, and S24 whereas the nonattenuated Dakar 1279 HeLa p6
      virus did not gain the vaccine epitope, retained the wild-type epitopes, and
      showed no other physical epitope alterations. MAb neutralization-resistant (MAbr)
      escape variants generated by using wild-type-specific MAbs S18 and S24 were found
      to lose the epitopes recognized by MAbs S18 and S24 and to acquire the epitope
      recognized by vaccine-specific MAb H5. In addition, the MAbr variants became
      attenuated for mice. Thus, the data presented in this paper indicate that
      acquisition of vaccine epitopes and loss of wild-type epitopes on the envelope
      protein are directly involved in the attenuation process of YF virus and suggest
      that the envelope protein is one of the genes encoding determinants of YF virus
      pathogenicity.

PMID- 1376367
TI  - Mechanisms of antibody-mediated protection against lymphocytic choriomeningitis
      virus infection: mother-to-baby transfer of humoral protection.
AB  - The role of antiviral antibodies in resistance to lymphocytic choriomeningitis
      virus (LCMV) infection was explored. Immune serum and monoclonal antibodies
      prevented fatal T-cell-mediated immunopathology following acute LCMV infections.
      In addition, 10- and 14-day-old mice that received maternally derived anti-LCMV
      antibodies through nursing were protected from an otherwise lethal LCMV
      challenge. Detailed investigation of the mechanism(s) by which these antiviral
      antibodies provided was carried out by using anti-LCMV monoclonal antibodies.
      Protection correlated directly with the ability of the antibodies to reduce viral
      titers in the tissues of conventional (K. E. Wright and M. J. Buchmeier, J.
      Virol. 65:3001-3006, 1991) and nude mice. However, this reduction was not simply
      a reflection of virus neutralizing activity, since not all antibodies which
      neutralized in vitro were protective. A correlation was also found between
      immunoglobulin isotype and protection: all of the protective antibodies were
      immunoglobulin G2a (IgG2a), while IgG1 antibodies mapping to the same epitopes
      were not. Protection appeared to be associated with events controlled by the Fc
      region. Functional F(ab')2 fragments which retained in vitro neutralizing
      activity were not protective in vivo. Furthermore, this Fc-associated function
      was not related to complement-mediated cell lysis, since C5-deficient mouse
      strains were also protected. These results suggest a role for antibody in
      protection from arenavirus infections and indicate that a distinct immunoglobulin
      subclass, IgG2a, may be essential for this protection.

PMID- 1376369
TI  - When retroviral reverse transcriptases reach the end of their RNA templates.
AB  - Luo and Taylor (J. Virol. 64:4321-4328, 1990) have previously shown that when,
      during RNA-directed DNA synthesis, a retroviral reverse transcriptase comes to a
      halt at the end of an RNA template, the associated RNase H produces a specific
      oligonucleotide that contains the 5' end of that template; in those studies the
      length of the oligonucleotide was predominantly 17 nucleotides. We have now
      investigated variables that might affect the formation and length of such a
      terminal oligonucleotide. We found small but significant variations in the length
      could be caused by the choice of reaction conditions and also the sources of
      reverse transcriptase and RNA template. Nevertheless, the general finding in all
      these situations was that RNase H acted at or about 14 to 18 nucleotides from the
      5' end, thereby supporting the interpretation that in the reverse transcriptase,
      the cleavage site for the RNase H is held at around this distance behind the DNA
      polymerase activity. In other words, it appears that for the intact protein, the
      RNase H and reverse transcriptase activities may work in a coupled or coordinate
      manner. We also found that more than 80% of the residual 5' oligonucleotides
      remained base paired to the RNA-directed DNA product. Furthermore, under certain
      conditions, these short RNAs could act as efficient primers for an associated DNA
      directed DNA synthesis in the reverse direction.

PMID- 1376371
TI  - Molecular basis of antigenic structures of poliovirus: implications for their
      evolution during morphogenesis.
AB  - Neutralizing monoclonal antibodies against poliovirus type 1 were obtained after
      conventional immunization or combined in vivo-in vitro immunization. Antibody
      binding sites were determined by sequence analysis of neutralization-resistant
      mutants. Site 3 variants had several amino acid substitutions in previously
      unidentified positions for neutralization resistance. Evidence for a linkage of
      subsites 3a and 3b is presented. Some site 3b antibodies as defined previously
      precipitated 14S subunits, although with reduced titers.

PMID- 1376372
TI  - [Electron-microscopic observations on rat lungs after long term inhalation of
      diesel emissions--non-neoplastic lesions].
AB  - Non-neoplastic lesions in the respiratory organs of rats (F344) were investigated
      after exposure to heavy and light duty diesel emissions for 30 months.
      Pathological examinations of the lungs after every 6 months of exposure were
      performed by light and electron microscopy. Anthracosis caused by the inhaled
      diesel soot was the main morphological change observed in the lung. Foci of
      alveoli filled with alveolar macrophages engorged with diesel particles were
      scattered in the lung parenchyma. Marked changes observed in these areas
      consisted of intake of diesel particles by type 1 epithelium, hypertrophy and
      glandular proliferation of type 2 epithelium with many extended microvilli and
      increased number and size of lamellar inclusion bodies, focal increase of
      collagen fibers in the interstitium, and infiltration of particle-laden
      macrophages, neutrophils, mast cells and plasma cells into the interstitium of
      alveolar septa. Within the alveolar lumina there was marked accumulation of
      particle-laden macrophages or neutrophils and their debris, as well as laminated
      or scrolled materials discharged from the type 2 epithelium. The most marked
      changes observed in the airways were focal shortening of cilia and protrusions of
      non-ciliated cells, which were attributable mainly to the effects of gaseous
      components in the diesel exhaust. These morphological changes appeared in all the
      groups exposed to particle concentrations greater than 1 mg/m3 after 6 months'
      exposure, and were more marked with increase in particle concentration and with
      time.

PMID- 1376370
TI  - Constitutive expression of an ISGF2/IRF1 transgene leads to interferon
      independent activation of interferon-inducible genes and resistance to virus
      infection.
AB  - Interferon (IFN)-stimulated gene factor 2 (ISGF2) plays a role in transcription
      of the beta IFN (IFN-beta) gene and IFN-stimulated genes (ISGs) and may function
      as a central mediator of cytokine responses. Constitutive ISGF2 transgene
      expression resulted in substantial resistance to three RNA virus families. This
      phenotype was not a consequence of IFN production and may have arisen directly
      through ISG expression. ISGF2 acted generally as a positive transcription factor
      through binding sites from several genes, in the context of transient
      cotransfection. Constitutive transcription of the endogenous IFN-beta gene, and
      several genes that are normally induced by either IFN-alpha or IFN-gamma, or only
      by IFN-alpha, was elevated in cells that constitutively express an ISGF2
      transgene. However, constitutive and virus-induced levels of IFN-beta mRNA were
      unaffected in such cell lines.

PMID- 1376373
TI  - [The sequential changes of serum acute phase reactants in response to
      antituberculous chemotherapy].
AB  - In order to evaluate the clinical effectiveness of response to antituberculous
      chemotherapy, we measured the serum levels such of acute phase reactants as C
      reactive protein (CRP), alpha-1-acid glycoprotein (alpha 1-AG), haptoglobin,
      alpha-1-antitrypsin (alpha 1-AT) and sialic acid in 24 patients with pulmonary
      tuberculosis. Furthermore the relationship between these parameters and other
      biochemical indicators, such as serum immunoglobulins (IgG, IgA and IgM) and
      blood erythrocyte sedimentation rate (ESR) were observed. In the case studies of
      the eighteen prognostically cured patients, the serum levels of alpha 1-AG,
      haptoglobin, alpha 1-AT and sialic acid were significantly higher than those of
      healthy controls (P less than 0.01), and were significantly decreased to normal
      levels within three to five weeks after negative results for tubercule bacilli
      were obtained in the sputum cultures, while CRP, immunoglobulin and ESR showed a
      tendency to be lower than the healthy controls. In conclusion, alpha 1-AG,
      haptoglobin, alpha 1-AT and sialic acid are considered to be the sensitive
      biochemical indicators capable of being used to predict and monitor the clinical
      response to antituberculous chemotherapy.

PMID- 1376374
TI  - Comparison of immune response potentiation and in vivo inflammatory effects of
      Freund's and RIBI adjuvants in mice.
AB  - Freund's adjuvant and the RIBI adjuvant system were compared for their immune
      potentiating and toxic effects. Each adjuvant was administered with
      benzo(a)pyrene (BaP), a nonimmunogenic hapten, conjugated to a bovine gamma
      globulin (BGG) carrier protein to 10 mice intraperitoneally. Complete Freund's
      adjuvant was used at initial immunization, while incomplete Freund's was used for
      booster immunizations. Five mice were given the immunogen conjugate (BaP-BGG) in
      saline as a control. Antibody titers were determined by ELISA to both hapten and
      carrier after each of the two booster immunizations. Titers to BaP were 2- and 27
      fold higher for RIBI than for Freund's after each of two booster immunizations.
      Titers to bGG were 119 and 12-fold higher for RIBI compared with Freund's. Titers
      to both immunogens were markedly less when administered in saline. Body weights
      were monitored in all three groups for the duration of the study. No differences
      were observed among the three groups. Mice from each group were euthanized at
      regular intervals to assess pathology. Splenic weight:body weight ratios were
      determined at the time of necropsy, and no differences were noted among the three
      groups. Granulomatous inflammatory lesions were most severe in the Freund's
      immunized mice, less severe in those immunized with RIBI, and least with saline.
      Results indicate that the RIBI system was more effective in potentiating an
      immune response and elicited less tissue reaction than did Freund's adjuvant with
      this particular immunogen.

PMID- 1376375
TI  - Normal human synovial fluid and articular cartilage contain similar intact
      proteoglycans.
AB  - This work, directed to characterization of proteoglycans present in normal human
      synovial fluid by Western blotting techniques, revealed an intimate relationship
      of these proteoglycans to those of articular cartilage. Analyses were performed
      on samples subjected to digestion with chondroitinase ABC, in the presence or
      absence of keratanase, yielding products containing core proteins with
      glycosaminoglycan side chain stubs. The proteoglycan core proteins contained
      epitopes reactive with monoclonal antibodies that distinguish between chondroitin
      sulfate-4 and chondroitin sulfate-6. Additionally, these products reacted with
      monoclonal antibody to keratan sulfate when keratanase was omitted from the
      digestion. The analysis of synovial fluid revealed that the proteoglycan core
      proteins expressed predominantly the chondroitin sulfate-6 epitope, with
      expression of the chondroitin sulfate-4 epitope demonstrable only in prepubertal
      individuals. There was coexpression of both chondroitin sulfate epitopes in all
      proteoglycan core proteins of prepubertal individuals. Coexpression of
      chondroitin sulfate and keratan sulfate epitopes occurred in all proteoglycan
      core proteins. Proteoglycan core proteins had M(r) similar to those obtained from
      articular cartilage. Hence, in individuals free of joint disease, most
      proteoglycans seem to be transferred from articular cartilage to the synovial
      fluid without major alteration in the apparent size of the proteoglycan core
      protein. Only a minor set of proteoglycan core proteins had no direct articular
      cartilage equivalent. As this set also contained keratan sulfate, it is likely to
      be of articular cartilage origin, but probably modified by proteolysis.

PMID- 1376376
TI  - Recombinant alpha-2b-interferon may restore natural-killer activity in patients
      with B-chronic lymphocytic leukemia.
AB  - In nine patients with CLL treated with chlorambucil followed by alpha-2b
      interferon (alpha 2b-IFN), T, B and natural killer (NK) cells and NK activity
      were studied before entering the study, after chlorambucil treatment, and after
      administration of alpha 2b-IFN. When considered as a whole, basal NK activity was
      lower in CLL patients than in controls (21.0% +/- 10.9 versus 40.2% +/- 17.4, p
      less than 0.001); however, when considered individually, four out of nine
      patients had normal NK activity at diagnosis. Chlorambucil did not increase
      global NK activity (21.7% +/- 7.1), whereas alpha 2b-IFN did so (44.3% +/- 19.1).
      After alpha 2b-IFN only one of seven patients studied had low NK activity.
      Previously increased absolute counts of CD2+, CD4+, CD8+, CD16+, CD57+
      lymphocytes were reversed with chlorambucil treatment to normal levels, while
      after this therapy CD11b+ and CD19+ cells decreased without reaching normal
      values. During alpha 2b-IFN therapy, an increase up to normal levels in the
      percentage of CD16+ (2.7% +/- 3.4 versus 7.7% +/- 6.5, p = 0.04) and CD57+ (3.0%
      +/- 3.0 versus 8.1% +/- 6.2, p = 0.020) lymphocytes was observed whereas the
      absolute number of CD19+ B-cells further decreased (5.2 x 10(9)/l +/- 2.5 vs 3.8
      x 10(9)/l +/- 2.3), albeit not significantly.

PMID- 1376377
TI  - Maintenance of Philadelphia-chromosome-positive progenitors in long-term marrow
      cultures from patients with advanced chronic myeloid leukemia.
AB  - We investigated the marrows of 19 patients with advanced Philadelphia chromosome
      positive (Ph+) chronic myeloid leukemia (CML) in long-term marrow culture (LTMC)
      to determine the frequency of loss of clonogenic leukemic cells in vitro. Sixteen
      patients were in first chronic phase at a median of 24 months from diagnosis and
      had received prior therapy with busulphan and/or hydroxyurea. The effect of
      interferon therapy on loss of Ph+ clonogenic cells in LTMC was also investigated.
      Of 16 patients who had not previously received interferon, complete loss of Ph+
      progenitors was documented by 4-5 weeks in the LTMCs from two (12.5%). Ph+
      progenitors persisted at 4-5 weeks in the LTMC derived from 12 patients. Marrows
      from nine patients treated with interferon were also established in LTMC.
      Cultures from four patients did not yield colonies with detectable metaphases at
      3-5 weeks, while Ph+ clones were present in the cultures initiated with marrows
      from five patients. Mean hematopoietic colony yields from the adherent layer at 2
      4 weeks, and from the supernatant layer at 1-3 weeks, of cultures derived from
      interferon-treated patients were significantly lower than in LTMCs of patients
      not treated with interferon (p less than 0.05). The results indicate that in
      previously treated patients with late chronic phase CML there is a low frequency
      of conversion of Ph-negative hematopoiesis in long-term culture. Interferon
      therapy is associated with impaired progenitor yields in LTMC and does not
      improve selective loss of Ph+ progenitors.

PMID- 1376378
TI  - Role of autocrine and paracrine production of granulocyte-macrophage colony
      stimulating factor and interleukin-1 beta in the autonomous growth of acute
      myeloblastic leukaemia cells--studies using purified CD34-positive cells.
AB  - The blast cells from some patients with acute myeloblastic leukemia (AML)
      proliferate autonomously in vitro. We have previously identified four groups of
      AML blasts based upon their growth characteristics in vitro, in particular the
      degree of autonomous growth. We have now measured the production of granulocyte
      macrophage colony-stimulating factor (GM-CSF) and interleukin-1 beta (IL-1 beta)
      by AML cells with different growth characteristics, using two sensitive enzyme
      linked immunosorbent assays. Our results show a correlation between the capacity
      of AML blasts to produce GM-CSF and IL-1 beta and the ability to grow
      autonomously in vitro. Blasts from cells with no autonomous growth (n = 5)
      secreted low or undetectable amounts of GM-CSF and IL-1 beta. Blasts with totally
      autonomous growth (n = 10) secreted the highest levels of GM-CSF (mean 2469
      pg/10(3) cells) and IL-1 beta (mean 3156 pg/10(6) cells). Whereas blasts with
      partially autonomous growth (n = 9) secreted intermediate levels of GM-CSF (mean
      270 pg/10(6) cells) and IL-1 beta (mean 931 pg/10(6) cells). In order to
      determine whether GM-CSF production was autocrine or the consequence of paracrine
      secretion by differentiated leukemic cells, we studied the degree of autonomous
      growth and production of GM-CSF by CD34-positive blasts from eight patients whose
      unfractionated cells produced GM-CSF. We found that CD34-positive blasts from six
      of these cases grew autonomously to a degree comparable to that of the
      unfractionated cells, and that CD34-positive blasts produced GM-CSF either
      autonomously or in response to recombinant IL-1 beta. Our data suggests that in
      the majority of cases, CD34-positive blasts are capable of autonomous growth and
      autocrine GM-CSF production, however this is variably regulated by the paracrine
      production of IL-1 beta by CD34-negative cells.

PMID- 1376379
TI  - Effect of human interleukin 3 on the susceptibility of fresh leukemia cells to
      interleukin-2-induced lymphokine activated killing activity.
AB  - Pretreatment of acute myeloblastic leukemia cells with the hemopoietic growth
      factor interleukin 3 (IL3) increased their susceptibility to lymphokine activated
      killing (LAK) but did not affect their constitutive resistance to native natural
      killer activity. In addition, IL3 treatment did not alter the LAK cell-mediated
      killing of CD34+ hemopoietic progenitors present in normal bone marrow. Increased
      3H-thymidine uptake was generally observed after IL3 treatment. However, failure
      to proliferate in response to IL3, observed in some cases, did not prevent
      changes in LAK susceptibility. Enhanced lysis of IL3-treated leukemic cells was
      accompanied by a moderate increase of the effector-target binding. Increased LAK
      susceptibility was already observed at 18 h, while optimal cytolysis and
      expression of the cell adhesion molecule (CAM) LFA-3 (CD58) by IL3-treated AML
      cells were concomitantly observed at later culture times. In contrast, the CAM
      ICAM-1 (CD54) was not modulated by IL3, nor were significant changes in the
      expression of either CAMs observed in normal hemopoietic cells. Blocking
      experiments with the anti-CD58 monoclonal antibody demonstrated a variable
      neutralizing effect on the IL3-induced increase of LAK activity, depending on the
      leukemia cell studied. The effect described here, together with the known role of
      IL3 in normal hemopoiesis makes it a factor of potential therapeutic value for
      the treatment of leukemic patients.

PMID- 1376380
TI  - Non-Hodgkin's lymphoma associated with human immunodeficiency virus: treatment
      with LNH 84 regimen in a selected group of patients.

PMID- 1376381
TI  - Propagation and characterization of novel canine lentivirus isolated from a dog.
AB  - We have recently isolated a novel canine lentivirus (canine immunodeficiency
      virus, [CIV]) from a leukemic dog. The virus was isolated from buffy coat cells
      obtained from the leukemic dog co-cultivated with indicator cells. The virus
      particles encode a reverse transcriptase with a preference for magnesium, have a
      density of 1.16 g/ml in sucrose, and induce syncytia in permissive cell lines
      such as Himalayan tahr ovary and canine fetal thymus. CIV replicates to high
      titer and highly purified virus can readily be prepared. The ultrastructure and
      morphogenesis of CIV is strikingly similar to that displayed by other
      lentiviruses, while immunoblot analysis failed to demonstrate close immunological
      relatedness to any other lentivirus or oncovirus. These findings suggest that
      this canine virus, representing the first isolation of a canine retrovirus,
      belongs to the lentivirus subfamily but is not closely related to other known
      members.

PMID- 1376382
TI  - Differential age-change in the numbers of CD4+CD45RA+ and CD4+CD29+ T cell
      subsets in human peripheral blood.
AB  - Peripheral blood mononuclear cells were obtained from people ranging in age from
      newborn to 102 years old and analyzed by dual color flow cytometer in terms of
      number and percentage of various subsets of T cells, B cells and natural killer
      cells (CD3, 4, 5, 8, 11b, 19, 20, 21, 25, 29, 45RA and 56). Numbers of T cells
      (CD3+ or CD5+ cells) significantly declined at the 3rd decade as compared with
      those of younger people, stayed at a relatively constant level between the 3rd
      and the 7th decade and gradually declined thereafter. In T cell subsets, both CD4
      and CD8 positive positive cells decreased with age, but a decrease was more
      pronounced in the latter, showing an age-related increase of CD4/CD8 ratio. The
      most interesting finding was a contrasting age-change in two subsets of CD4+ T
      cells; i.e. a subset of suppressor inducer T cells (CD4+CD45RA+ naive cells)
      decreased with age, while a subset of helper inducer T cells (CD4+CD29+ memory
      cells) increased with age. CD20+ B cells also decreased with age in a manner
      similar to that observed in T cells. Natural killer cells (CD56) showed an
      increase in numbers with age. The relationship between these changes in various
      subsets of peripheral blood leukocytes and the age-related decline in immune
      functions has been discussed.

PMID- 1376383
TI  - [The specific prostatic antigen: an element of diagnostic conflict?].

PMID- 1376384
TI  - B-cell subsets and platelet counts in HIV-1 seropositive subjects.
AB  - A subset of B lymphocytes positive for the CD5 antigen have been implicated in
      several autoimmune disorders. To investigate their role in human immunodeficiency
      virus type 1 (HIV-1) infection, we studied peripheral-blood B and T lymphocytes
      from HIV-1-positive patients with (n = 13) and without (n = 18) thrombocytopenia,
      8 patients with classic autoimmune thrombocytopenia, and 16 healthy controls. The
      proportion of CD5-positive B cells was significantly higher in the HIV-1-positive
      thrombocytopenic patients than in the healthy controls, as a result of both
      higher numbers of CD5-positive B cells and lower numbers of CD5-negative B cells.
      Platelet count was positively correlated with CD5-negative B-cell count (r = 0.6,
      p less than 0.001) and negatively correlated with proportion of B cells that were
      CD5 positive (r = -0.5, p less than 0.01) among the HIV-1-positive patients. The
      high concentrations of IgM-containing immune complexes in HIV-1-positive patients
      with autoimmune disorders may be due to changes in the CD5-positive B-cell
      subset.

PMID- 1376385
TI  - Fontan procedure.

PMID- 1376386
TI  - Biology of tumour metastasis.

PMID- 1376387
TI  - Free beta-hCG as first-trimester marker for fetal trisomy.

PMID- 1376388
TI  - Ear canal cholesteatoma.
AB  - Although cholesteatomas are more commonly found in the middle ear and the
      mastoid, the disease can occur in the external ear canal. All cases of ear canal
      cholesteatoma treated by the author were reviewed. There were nine ears in seven
      patients, who had an average age of 62 years. The lesions ranged in size from a
      few millimeters to extensive mastoid destruction. Smaller lesions can be managed
      by frequent cleaning as an office procedure. Larger lesions require surgery,
      either canaloplasty or mastoidectomy. The otolaryngologist should suspect this
      disease in the elderly. Microscopic examination of the ear with meticulous
      cleaning of all wax, especially in elderly patients, is most useful in detecting
      early disease. Frequent applications of mineral oil to the canal should be used
      in the management of the disease and to prevent recurrence.

PMID- 1376389
TI  - [Hodgkin's disease in French Polynesia. 7 cases observed at the Territorial
      Hospital Center from 1985 to 1990].
AB  - Seven Polynesians suffered from Hodgkin's disease were admitted in the
      territorial Hospital Center in 6 years. They came from different Polynesian
      archipelagos. Three of them are 30 years old and 3 are 40 years old. Diagnosis is
      based on an histological test, but has to be confirmed by a center specialized in
      lymphomae investigations since a scanner has been installed at the Territorial
      Hospital Center of Papeete (March 1987) results are satisfactory: echography and
      abdominal scanner lymphography and thoracic scanner osteoma medullare biopsy and
      liver biopsy puncture. Six patients presented a diffuse lesion (III B or IV) and
      one an intermediary phase (II B2). Treatment started by chemotherapy MOPP and
      ABVD alternatively. Four patients out of seven did not continue their treatment
      up to the end; one patient aged 34, after six treatments by MOPP and a recovering
      treatment by MIME got an autograft of bone marrow in Paris in October 1989, and
      he is actually in a good shape. Most of the patients are out of control.
      Application of complex therapeutic protocols during several months and inducing
      side effects, demands a large agreement of both patients and relatives. That is
      very rarely got nowadays.

PMID- 1376391
TI  - Effects of interferon alpha on murine cytomegalovirus replication.
AB  - The present study examined the protective effect of IFN-alpha against mouse
      cytomegalovirus (MCMV) infection in embryo fibroblasts (MEF) of genetically
      resistant (C3H/HeJ) and susceptible (C57BL/6) mouse strains. At a M.O.I. of 1 IFN
      alpha was protective in C3H/HeJ-MEF but not in C57BL/6-MEF. Dot-blot analysis
      during MCMV replication in C3H/HeJ-MEF showed that IFN-alpha pretreatment reduced
      the steady state level of immediate early and late mRNAs but partially reduced
      early gene expression.

PMID- 1376392
TI  - Purification and characterization of heterologous component IIs of botulinum C2
      toxin.
AB  - Botulinum C2 toxin (C2T) elaborated by certain strains of Clostridium botulinum
      types C and D is composed of separate and dissimilar two proteins, components I
      and II. Previous studies have shown that these two components of C2T produced by
      type C and D strains were immunologically heterologous and that C2T-producers
      were classified into three groups depending on the difference in molecular
      characteristics of the components I and II. In the present study, the
      heterologous component IIs of C2T were purified from three representative strains
      of the groups and the molecular characteristics of the components were compared.
      Immunological analyses by agar gel double immunodiffusion test showed that the
      component IIs purified from the three strains have the specific epitope(s) in
      addition to the common one(s). The biological activity of C2Ts reconstituted with
      component I purified from a fixed strain and component II each from the three
      strains differed depending on the source of the component II. These results
      indicate that the component II of C2T produced by C. botulinum types C and D
      differs in molecular structure, which reflects on the difference in the
      biological activity of the toxin. The present study suggests that the
      pathophysiological activity of C2T, which possibly causes a necrotic enteritis,
      is dependent on the C2T-producing bacteria infected.

PMID- 1376390
TI  - Conjugative transfer functions of broad-host-range plasmid RK2 are coregulated
      with vegetative replication.
AB  - The kilB locus (which is unclonable in the absence of korB) of broad-host-range
      plasmid RK2 (60 kb) lies between the trfA operon (co-ordinates 16.4 to 18.2 kb),
      which encodes a protein essential for vegetative replication, and the Tra2 block
      of conjugative transfer genes (co-ordinates 20.0 to 27.0 kb). Promoter probe
      studies indicated that kilB is transcribed clockwise from a region containing
      closely spaced divergent promoters, one of which is the trfA promoter. The
      repression of both promoters by korB suggested that kilB may also play a role in
      stable maintenance of RK2. We have sequenced the region containing kilB and
      analysed it by deletion and insertion mutagenesis. Loss of the KilB+ phenotype
      does not result in decreased stability of mini RK2 plasmids. However insertion in
      ORFI (kilBI) of the region analysed results in a Tra- phenotype in plasmids which
      are otherwise competent for transfer, demonstrating that this locus is essential
      for transfer and is probably the first gene of the Tra2 region. From the kilBI
      DNA sequence KilBI is predicted to be 34995 Da, in line with M(r) = 36,000
      observed by sodium dodecyl sulphate/polyacrylamide gel electrophoresis, and
      contains a type I ATP-binding motif. The purified product was used to raise
      antibody which allowed the level of KilBI produced from RK2 to be estimated at
      approximately 2000 molecules per bacterium. Protein sequence comparisons showed
      the highest homology score with VirB11, which is essential for the transfer of
      the Agrobacterium tumefaciens Ti plasmid DNA from bacteria to plant cells. The
      sequence similarity of both KilBI and VirB11 to a family of protein export
      functions suggested that KilBI may be involved in assembly of the surface
      associated Tra functions. The data presented in this paper provide the first
      demonstration of coregulation of genes required for vegetative replication and
      conjugative transfer on a bacterial plasmid.

PMID- 1376393
TI  - Molecular analysis of virus-producing and non-producing clones derived from a
      defective SSPE virus Yamagata-1 strain.
AB  - Two virus clones were isolated from a defective SSPE virus, the Yamagata-1
      strain, and designated as the YA and YF clones. The YA clone-infected cells
      produced neither cell-free virus nor cell-associated virus, whereas the YF clone
      infected cells produced both cell-associated and cell-free virus. No difference
      of epitopes on structural proteins was observed between these two clones. Both
      clones had hemadsorption activity. Quantitation of structural protein by Western
      dot blots showed relatively a lower amount of M protein in the YA-infected cells
      than that in the YF-infected cells. The ratio, P plus M dicistronic/M
      monocistronic mRNA, in the YA-infected cells was about twice that in the YF
      infected cells. Sequence analysis of cDNA corresponding to P plus M dicistronic
      mRNA revealed that the deduced M protein of the YF virus was smaller than that of
      the YA virus by five amino acids from the carboxy terminal. These results suggest
      that abundant production of P plus M dicistronic mRNA is responsible for the
      reduced amount of M protein in the non-productive YA clone.

PMID- 1376394
TI  - Generation of helper T cells that recognize a cross-reactive idiotype through a
      network mechanism.
AB  - T cells that recognize the cross-reactive idiotype expressed on the heavy (H)
      chain of M104E (IgM, lambda 1) were induced in BALB/c mice by immunization with
      Dextran B-1355. T cells derived from mice immunized with 1 mg of Dextran B-1355
      showed a marked proliferative response against M104E, whereas T cells from mice
      immunized with Ficoll or lesser amounts of Dextran B-1355 did not. BCL1Id, which
      had an immunoglobulin isotype identical to M104E, did not induce proliferation of
      the T cells. These T cells also proliferated against J558 (IgA, lambda 1) which
      shared the cross-reactive idiotype of the anti-alpha (1----3) glucosidic linkage
      antibody with M104E on the H chain. The T cells proliferated more efficiently
      against F(ab')2-104E, Fab-104E and H104E, the H chain of M104E, than against
      intact M104E. The T cell proliferative response against the idiotype on M104E or
      even H104E required macrophages as antigen-presenting cells (APC) and the
      response was inhibited when APC were treated with NH4Cl or chloroquine,
      inhibitors of antigen processing. Moreover, anti-CD4 antibody or anti-Ia antibody
      inhibited the proliferative response. These results indicated that anti-idiotypic
      T cells of the helper type, which recognized a cross-reactive idiotype associated
      with Ia molecules in processed form, could be induced physiologically through a
      network mechanism.

PMID- 1376395
TI  - Lateral flagella of vibrios: serological classification and genetical similarity.
AB  - Lateral (L-) flagella-having vibrios were classified into 13 H-serogroups
      (flagellar antigen serogroups) by means of H-agglutination test. Vibrio
      parahaemolyticus was classified into 3 serogroups, HL1 to 3. V. alginolyticus and
      V. harveyi were classified into 5 and 3 serogroups, respectively, but 2 of those
      were serogroups common to the both species. V. fluvialis and V. furnissii
      constituted a same serogroup, HL8. Cross-reactivity between each serogroup was
      not observed in H-agglutination test, although some cross-reactivity was observed
      in gel diffusion test. Furthermore, similarity of DNA sequence of L-flagellar
      structure gene was demonstrated by dot blot hybridization test with a DNA probe
      of HL2 L-flagellar gene fragment. These results suggest conservation of DNA
      sequence of the L-flagellar gene of vibrios.

PMID- 1376396
TI  - Interferons: costly but effective.

PMID- 1376398
TI  - Interferon treatment for chronic viral hepatitis in Australia: is it worth it?

PMID- 1376397
TI  - The clinical application of the interferons: a review. NSW Therapeutic Assessment
      Group.
AB  - OBJECTIVES: To review the clinical information on the use of alpha, beta and
      gamma interferons and to classify the use of alpha interferons in Australia
      according to approved indications, indications for which there is good supporting
      evidence and indications where therapy is under investigation; and to estimate
      the cost of therapy with alpha interferons in New South Wales in 1991. DATA
      SOURCES: Data were obtained from computerised literature searches. DATA
      EXTRACTION: A position paper was drafted on behalf of the NSW Therapeutic
      Assessment Group (NSWTAG). This was circulated to clinicians identified as having
      a particular interest in the use of the interferons in major NSW teaching
      hospitals, for comment and amendment where necessary. CONCLUSIONS: Two forms of
      alpha interferon, interferon alfa-2b and interferon alfa-2a have been approved
      for use in Australia, interferon alfa-2b for use in the management of hairy cell
      leukaemia and condylomata acuminata and interferon alfa-2a for use in the
      management of hairy cell leukaemia and human immunodeficiency virus (HIV) related
      Kaposi's sarcoma. Applications have been lodged for the use of interferon alfa-2b
      in HIV related Kaposi's sarcoma, cutaneous basal cell carcinoma and hepatitis B
      and C and for the use of interferon alfa-2a in the management of hepatitis B,
      cutaneous T-cell lymphoma and metastatic renal cancer. Interferon alfa-n1 is not
      available in Australia except for use in a clinical trial in patients who are HIV
      seropositive. The use of the alpha interferons is currently under investigation
      in a wide variety of other diseases, with the likelihood that other indications
      will soon be established. However, the alpha interferons are generally not
      regarded as first line agents. Beta and gamma interferons have been studied less
      intensively than the alpha interferons, but it is likely that selected
      applications for their use will also be defined with the passage of time.

PMID- 1376399
TI  - A role for dextran in pseudomyxoma peritonei?

PMID- 1376400
TI  - Laser prostatectomy.

PMID- 1376401
TI  - Isolation and characterization of cDNA clones encoding cdc2 homologues from Oryza
      sativa: a functional homologue and cognate variants.
AB  - Using probes obtained by PCR amplification, we have isolated two cognate rice
      cDNAs (cdc2Os-1 and cdc2Os-2) encoding structural homologues of the cdc2+/CDC28
      (cdc2) protein kinase from a cDNA library prepared from cultured rice cells.
      Comparison of the deduced amino acid sequences of cdc2Os-1 and cdc2Os-2 showed
      that they are 83% identical. They are 62% identical to CDC28 of Saccharomyces
      cerevisiae and much more similar to the yeast and mammalian p34cdc2 kinases than
      to rice R2, a cdc2-related kinase isolated previously by screening the same rice
      cDNA library with a different oligonucleotide probe. Southern blot analysis
      indicated that the three rice clones (cdc2Os-1, cdc2Os-2 and R2) are derived from
      distinct genes and are each found in a single copy per rice haploid genome. RNA
      blot analysis revealed that these genes are expressed in proliferating rice cells
      and in young rice seedlings. cdc2Os-1 could complement a temperature-sensitive
      yeast mutant of cdc28. However, despite the similarity in structure, both cdc2Os
      2 and R2 were unable to complement the same mutant. Thus, the present results
      demonstrate the presence of structurally related, but functionally distinct
      cognates of the cdc2 cell cycle kinase in rice.

PMID- 1376402
TI  - Isolation and characterization of a cDNA from Cuphea lanceolata encoding a beta
      ketoacyl-ACP reductase.
AB  - A cDNA encoding beta-ketoacyl-ACP reductase (EC 1.1.1.100), an integral part of
      the fatty acid synthase type II, was cloned from Cuphea lanceolata. This cDNA of
      1276 bp codes for a polypeptide of 320 amino acids with 63 N-terminal residues
      presumably representing a transit peptide and 257 residues corresponding to the
      mature protein of 27 kDa. The encoded protein shows strong homology with the
      amino-terminal sequence and two tryptic peptides from avocado mesocarp beta
      ketoacyl-ACP reductase, and its total amino acid composition is highly similar to
      those of the beta-ketoacyl-ACP reductases of avocado and spinach. Amino acid
      sequence homologies to polyketide synthase, beta-ketoreductases and short-chain
      alcohol dehydrogenases are discussed. An engineered fusion protein lacking most
      of the transit peptide, which was produced in Escherichia coli, was isolated and
      proved to possess beta-ketoacyl-ACP reductase activity. Hybridization studies
      revealed that in C. lanceolata beta-ketoacyl-ACP reductase is encoded by a small
      family of at least two genes and that members of this family are expressed in
      roots, leaves, flowers and seeds.

PMID- 1376403
TI  - Amplification of substoichiometric recombinant mitochondrial DNA sequences in a
      nuclear, male sterile mutant regenerated from protoplast culture in Nicotiana
      sylvestris.
AB  - A Nicotiana sylvestris plant regenerated from protoplast culture was found to be
      mutated in both the mitochondrial (mt) and nuclear genomes. The novel mt DNA
      organization, called U, is due to the amplification of recombinant
      substoichiometric DNA sequences that preexist in the parent line. The
      recombination event involves two 404 bp repeats, which hybridize to a 2.1 kb
      transcript. Although the sequence of both repeats was not altered by the
      recombination, an additional transcript of 2.5 kb was detected in U mitochondria.
      In addition to this mitochondrial reorganization, the protoclone carried a
      recessive nuclear mutation conferring male sterility (ms4). A possible role of
      ms4 in the appearance of the U mt DNA organization was investigated by
      introducing this gene into normal N. sylvestris cytoplasm. No mt DNA change could
      be found in homozygous ms4/ms4 plants of the F2 generation.

PMID- 1376404
TI  - Retrotransposon families in rice.
AB  - Three families of retrotransposons of rice (Tos1, Tos2, and Tos3) were isolated
      by using a method based on the sequence conservation of the primer binding site
      for reverse transcription. This method should be generally applicable for cloning
      retrotransposon of other plants. One retrotransposon, Tos3-1, was studied in
      detail. Tos3-1 is 5.2 kb long, has structures common to retrotransposons, such as
      long terminal repeats (LTR), a primer binding site complementary to the initiator
      tRNA, a polypurine tract, and generates target sequence duplications flanking the
      inserted element. Southern blotting analysis showed that sequences homologous to
      Tos1, 2 and 3 are found in wild rice species as well as in cultivated rice
      species, but not in maize and tobacco. The copy number and genomic location of
      the families vary in different strains of one species of wild rice, suggesting
      that these elements may still be active. Retrotransposons were also screened for
      by amplification of the reverse transcriptase coding region using the polymerase
      chain reaction (PCR). At least two types of copia-like elements (Tos4 and Tos5)
      were found. The total copy number of retrotransposons in the rice genome was
      estimated to be about 1000. These results suggest that, as in Drosophila,
      retrotransposons are the major transposon class in rice.

PMID- 1376405
TI  - Structural and functional analysis of the Bz2 locus of Zea mays: characterization
      of overlapping transcripts.
AB  - Analysis of the transcription pattern of the Bz2 locus revealed that overlapping
      transcripts are derived from opposite DNA strands. The most abundant transcript
      (sense transcript) has an open reading frame coding for a protein of 241 amino
      acids, whilst in the antisense orientation no open reading frame has been
      detected; the antisense transcripts are detected only in those tissues that show
      high levels of sense transcript. Particle gun experiments indicate that the sense
      transcript is sufficient to provide the Bz2 function. The promoter driving the
      sense transcript contains the elements usually found in front of eukaryotic
      genes. In addition an element with similarity to the C1 and R binding sites
      identified in the Bz1 promoter is found. Further upstream in the promoter region
      a transposon-like insertion has been identified. This element has features
      similar to members of the Ac/Ds transposable element family. The putative Bz2
      protein shows similarity to various other plant proteins and to an Escherichia
      coli protein. All related proteins have in common the fact that they are involved
      in stress responses.

PMID- 1376406
TI  - The non-dosage compensated LSP1-alpha gene of Drosophila melanogaster lies
      immediately downstream of the dosage compensated L12 gene.
AB  - The X-linked gene LSP1-alpha of Drosophila melanogaster, expressed in the third
      larval instar, does not exhibit dosage compensation at its normal locus but does
      compensate when it is relocated to ectopic sites on the X chromosome. A
      transcription unit designated L12, which is active in the second larval instar
      and capable of encoding a putative protein of 28.5 kDa, lies immediately
      downstream from LSP1-alpha. We have determined that L12 is dosage compensated by
      measuring the steady-state level of its transcript in male and female larvae. The
      difference in response of these two adjacent genes should be taken into
      consideration when models of the mechanism of dosage compensation are formulated.

PMID- 1376407
TI  - Petunia plants escape from negative selection against a transgene by silencing
      the foreign DNA via methylation.
AB  - Transgenic Petunia hybrida clones harbouring the T-DNA gene 2 of Agrobacterium
      tumefaciens were used to test a strategy for the trapping of plant transposable
      elements. In the Petunia line used, floral variegation is due to the presence of
      the non-autonomous transposable element dTph1 at the An1 locus. The gene 2
      product converts the auxin precursor indole-3-acetamide and its analogue 1
      naphthalene acetamide into the active auxins indole-3-acetic acid and 1
      naphthalene acetic acid. Plant cells that express gene 2 can use a low
      concentration of the precursors as auxins and become sensitive to the toxicity of
      high concentrations of these compounds. By selecting protoplast-derived
      microcalli or seedlings able to grow on medium with high precursor
      concentrations, variant plants were obtained in which gene 2 was no longer
      expressed. Southern analysis, using gene 2-specific probes, revealed that in one
      variant the T-DNA was deleted. For 30 other variants no alteration in gene 2
      structure was observed, indicating that transposable element insertion was not
      responsible for the inactivation of gene 2. Analysis with restriction enzymes
      allowing discrimination between methylated or non-methylated DNA sequences showed
      that the inactivated gene 2 sequences were methylated. Addition of the in vivo
      methylation inhibitor 5-azacytidine to the medium led to reactivation of gene 2
      expression in some of the variants. These observations demonstrated that
      reversible DNA methylation was the main cause of silencing of gene 2 in this
      system.

PMID- 1376409
TI  - Deoxyribonuclease-hypersensitive sites in the glycoprotein hormone alpha-subunit
      gene from trophoblastic and nontrophoblastic human tumor cell lines: correlation
      with expression and effect of chemical inducers.
AB  - Human CG is composed of two subunits, alpha and beta. In addition to its eutopic
      synthesis in normal and malignant trophoblasts, the hormone is produced
      ectopically by a variety of tumor cell lines of nonplacental origin. Regulation
      of the alpha CG gene in trophoblasts appears to differ from that in
      nontrophoblasts. To determine whether these differences are reflected in the
      chromatin structure at the alpha CG locus, DNase I-hypersensitive sites within
      this domain were mapped in human tumor cell lines that differentially express the
      gene. Two hypersensitive sites were detected in DNA from cell lines that produce
      the alpha-subunit. The latter includes trophoblastic (JAr and JEG-3
      choriocarcinoma) and nontrophoblastic (HeLa cervical carcinoma and ChaGo
      bronchogenic carcinoma) tumor cell lines. The most prominent site (HS 1) was
      located approximately 100 base pairs upstream from the transcription start site.
      In trophoblasts, accessibility of HS 1 increased substantially upon induction of
      the gene by cAMP, likely reflecting alterations in DNA-protein interactions at
      the cAMP response element and/or tissue-specific enhancer. In nontrophoblasts,
      where alpha-subunit synthesis is enhanced by sodium butyrate but not by cAMP,
      neither butyrate nor cAMP altered the accessibility of HS 1. The HS 2 is
      comprised of multiple sites with weak to moderate DNase sensitivity located
      downstream at +1600 to +4000 in cell lines that produce alpha-subunit. Cell lines
      that do not express the alpha CG gene possess a distinct hypersensitive site (HS
      3) within the first intron at about +600; these include 3A-Sub-E (SV40
      transformed placenta), CBT (glioblastoma multiforme), and CaSki (cervical
      carcinoma). Cleavage by DNase at HS 1 and HS 2 is not evident in nuclei from cell
      lines that do not produce alpha-subunit. These results suggest that HS 1 and HS 3
      are characteristic of active and inactive states of the alpha CG gene,
      respectively, and that the accessibility of HS 1 generally correlates with the
      level of expression.

PMID- 1376408
TI  - Self-splicing of a mitochondrial group I intron from the cytochrome b gene of the
      ascomycete Podospora anserina.
AB  - We have shown that the second intron of the Podospora mitochondrial gene coding
      for cytochrome b (Cytb 12) splices autocatalytically, using in vitro transcripts
      generated from the T7 promoter. The reaction takes place at 37 degrees C in the
      presence of 50 mM TRIS-HCl pH 7.5, 60 mM MgCl2 and 1 mM GTP but shows a low
      efficiency even at high KCl concentrations of up to 1.2 M. Under these
      conditions, intron bI2 follows the conventional pathway of group I splicing, and
      all characteristic products, with regard to both transesterification and
      hydrolysis, could be identified. Moreover, the intron is capable of undergoing
      cyclization, thereby releasing the noncoded G and one additional nucleotide (U)
      from the 5' end. The 5' cleavage site is preceded by the same two nucleotides,
      indicating a base-pairing at the same site of the internal guide sequence (IGS)
      for both splicing and cyclization ("one-binding-site model"). In addition,
      products resulting from site-specific hydrolysis 138 nucleotides downstream of
      the 5' splice site were detected. Unusually, the shortened intron is also able to
      form a circular RNA and an alternative sequence that aligns the cyclization site
      to the catalytic core of the intron must be assumed.

PMID- 1376410
TI  - Transcriptional regulation of prostate kallikrein-like genes by androgen.
AB  - Using gene-specific synthetic oligonucleotides the expression and regulation of
      kallikrein-like genes in the human prostatic cancer cell line LNCaP were studied.
      Prostate-specific antigen (PSA) and human glandular kallikrein (hGK-1) together
      constitute a subfamily of serine proteases exclusively produced in the human
      prostate. RNA analysis revealed that both genes are expressed in LNCaP cells with
      PSA basal levels being 2-fold higher than hGK-1 levels. Both mRNAs are induced
      over a period of 24 h in the presence of 3.3 nM of the synthetic androgen
      mibolerone. Stimulation of PSA RNA is about 5-fold, whereas hGK-1 stimulation is
      less pronounced. Nuclear run-on analysis revealed that androgen induction of
      kallikrein-like genes in LNCaP cells is a rapid event (less than 3 h) occurring
      at the level of transcription initiation. Treatment of cells with cycloheximide
      demonstrates that, while PSA/hGK-1 basal transcription strictly depends on
      continuous protein synthesis, transcriptional induction by androgen does not.
      This suggests the direct involvement of the androgen receptor in the induction
      process independent of additional labile protein factors necessary for kallikrein
      basal transcription. A binding motif is present in the PSA and hGK-1 promoters,
      closely resembling the consensus sequence for steroid-responsive elements. The
      androgen antagonist cyproterone acetate was also able to stimulate transcription
      of kallikrein-like genes in LNCaP cells. In contrast, androgen-dependent
      transcriptional suppression of the protooncogene c-myc was strongly counteracted
      by cyproterone acetate. Thus, antiandrogens act differentially on androgen
      regulated prostate-specific (PSA, hGK-1) and growth-related (c-myc) gene
      expression in LNCaP cells.

PMID- 1376411
TI  - Structure of the human insulin-like growth factor binding protein-2 gene.
AB  - Insulin-like growth factors (IGFs) are polypeptide hormones with structural
      homology to proinsulin. IGFs circulate in blood bound to specific IGF binding
      proteins (IGFBPs). cDNA sequences of six members of a family of human and rat
      IGFBPs have been published. Here we present a partial characterization of the
      human IGFBP-2 gene. This single copy gene is located on chromosome 2 and spans a
      total of more than 32 kilobases (kb) of genomic sequence. It is organized in four
      exons with sizes of more than 568, 220, 141, and 496 nucleotides. The intron
      between exon one and exon two contributes 27 kb to the size of the IGFBP-2 gene.
      The second and the third introns comprise 1.1 kb and 1.95 kb, respectively. When
      the structure of the IGFBP-2 gene is compared to that of the IGFBP-1 and IGFBP-3
      genes, the exon boundaries are found to be conserved in these three genes. A
      single transcriptional start site was localized to 113 +/- 2 nucleotides 5' of
      the ATG start codon of IGFBP-2 translation. Furthermore, the region between
      nucleotides -635 and -2 upstream of the ATG was demonstrated to exhibit promoter
      activity in human Jurkat K16 cells. This region is devoid of TATA or CAAT
      consensus sequence motifs and has a high content of dC and dG nucleotides. In
      this respect the putative IGFBP-2 promoter region resembles the promoters which
      are often associated with housekeeping genes.

PMID- 1376412
TI  - Clonal analysis of murine B cell response to the human immunodeficiency virus
      type 1 (HIV1)-gag p17 and p25 antigens.
AB  - The antigenicity of HIV-gag p17 and p25 proteins was analyzed using a panel of 52
      monoclonal antibodies (mAb) derived from 17 independent fusion experiment
      protocols performed in 12 different laboratories. These mAb were tested for their
      capacity to bind peptides corresponding to sequences of HIV1-BRU-gag p17 and p25.
      Thirty-five overlapping peptides (P1 to P35) totally covering the p17 and p25
      proteins were used. This study allowed us to identify four immunodominant regions
      inducing B cell response, two on p17 corresponding to P2 and P13 (amino acids 11
      25 and 121-132, respectively) and two on p25 corresponding to P21 and P28-P29-P30
      (a.a. 201-218 and 285-320 respectively). According to secondary structure
      predictions, peptides P2 and P21 contained hydrophilic alpha helix folded regions
      whereas P13 sequence presented a beta turn propensity. These regions and the P28
      30 region were also predicted to be easily accessible to mAb. Several other p25
      derived peptides: P15 (a.a. 142-156), P16 (a.a. 148-162), P19 (a.a. 176-192), P22
      (a.a. 219-233) and P23 (a.a. 233-253) were recognized by mAb. No p17-derived
      peptide other than P2, P13 and P12 (a.a. 111-123) was found to react with mAb.
      Cross-blocking studies between mAb, suggested the existence of more than four
      distinct epitopic areas on p17 and eight on p25.

PMID- 1376413
TI  - Specific histamine release capacity of peptides selected from the modelized Der p
      I protein, a major allergen of Dermatophagoides pteronyssinus.
AB  - Dust mite allergens are considered as a major cause of allergic disease and as a
      risk factor for asthma. Der p I, a 222 amino-acid residue globular glycoprotein,
      is one of the major allergens from Dermatophagoides pteronyssinus (Dpt) mites. In
      this study, we have used predictive conventional algorithms (i.e. hydrophilicity,
      mobility, accessibility) and a three-dimensional model of Der p I derived from
      comparison to actinidin and papain to select continuous amino acid sequences as
      potential B cell epitopes. Four peptides, 52-71, 117-133, 176-187, 188-199 were
      synthesized. Their antigenic reactivity was investigated, mainly by measuring
      their capacity to induce in vitro histamine release. Results indicated that only
      Dpt-sensitive patients react specifically to Der p I-derived peptides and more
      frequently to 52-71 and 117-133. For each peptide, the intensity of response was
      dependent on the patient tested and on the peptide concn. The capacity of
      peptides to induce histamine release was demonstrated to be correlated with the
      serum level of anti-Der p I IgE (r = 0.86; p less than 10(-2)). Taken together
      these data emphasize, in Dpt-sensitive patients, the heterogeneity of the
      specific response to synthetic Der p I-derived peptides and underline the
      possible variety of epitopes belonging to the allergen Der p I.

PMID- 1376414
TI  - Repeated helical epitopes of defined amino acid sequence in human type III
      collagen identified by monoclonal antibodies.
AB  - Two monoclonal antibodies, designated 1F8 (IgG1) and 5B10 (IgG1), have been
      produced in mice against native human type III collagen. These antibodies were
      highly type and species specific, recognizing the triple helical domain of type
      III as tested by ELISA. Immunofluorescence studies using each of these antibodies
      resulted in a fibrous staining pattern in human skin dermis. Immunogold electron
      microscopy resulted in a periodic distribution of gold particulates along banded
      collagen fibrils. Assuming that the total contour length of pepsin digested type
      III collagen is 300 nm, measurements of antibody-antigen complexes visualized by
      rotary shadowing revealed that each antibody bound at the same two sites: one
      approximately at the middle of the helix (153 nm from the N-terminus), the other
      at a site one-quarter the triple helical length from the N-terminus (75 nm). That
      the one-quarter binding site was closest to the N-terminus was determined by
      antibody incubation following tadpole collagenase treatment, which results in a
      larger, N-terminus containing fragment (binding antibody) and a smaller C
      terminus containing fragment (not binding antibody). Located at each antibody
      binding epitope is a sequence of 10 amino acids: Gly-Ala-Hyp-Gly-Leu-Arg-Gly-Gly
      Ala-Gly. Renatured cyanogen bromide-cleaved(CB)-peptides, CB4 and CB8, containing
      these repeated sequences reacted with each antibody, whereas other renatured type
      III CB-peptides were unreactive as determined by Western blotting analysis and
      ELISA. This was further confirmed by inhibition tests using a 10 residue
      synthetic peptide of identical sequence, which yielded 20-30% inhibition of
      antibody binding to native type III collagen at 4 degrees C. However, no
      inhibition was noted at higher temperature. These results indicate that both
      monoclonal antibodies recognize a specific helical conformation of 10 or slightly
      fewer residues in the three identical polypeptide chains comprising type III
      collagen.

PMID- 1376416
TI  - Assessment of antimutagenicity and anticarcinogenicity--end-points and systems.

PMID- 1376415
TI  - Analysis of peptidic epitopes recognized by the three monoclonal antibodies
      specific for the same region of glycophorin A but showing different properties.
AB  - Analysis of epitopes for the three monoclonal antibodies (GPA105, GPA33, OSK4-1)
      against glycophorin A (GPA) was performed with the use of proteolytic fragments
      of GPA, the synthetic nonapeptide with the sequence of amino acid residues 35-43
      of GPA, and a series of peptides synthesized on plastic pins. The antibodies were
      specific for a short peptide sequence RAHE (a.a. 39-42 of GPA, MAbs GPA105 and
      OSK4-1) or RAHEV (a.a. 39-43 of GPA, MAb GPA33). Despite recognizing the same
      fragment of GPA, the three antibodies showed differences in fine specificity and
      in response to antigen desialylation. Reactions with single replacement analogs
      of the RAHEV sequence showed that immunodominant (unreplaceable) residues for the
      MAbs GPA33 and OSK4-1 were His and Glu, respectively, whereas no such residue was
      found for the MAb GPA105. Desialylation of the antigen gave strong enhancement of
      reactivity with the MAb GPA33, moderate--with the MAb GPA105, and weak or no
      enhancement of reaction with the MAb OSK4-1. The results showed that monoclonal
      antibodies directed against the same fragment of the polypeptide chain of densely
      glycosylated antigen may recognize different subsites which are masked at
      different degree by sialic acid residues.

PMID- 1376417
TI  - Assessment of antimutagenicity and anticarcinogenicity.

PMID- 1376418
TI  - Antimutagenicity profiles of some natural substances.
AB  - Selected antimutagenicity listings and profiles have been prepared from the
      literature on the antimutagenicity of retinoids and the carotenoid beta-carotene.
      The antimutagenicity profiles show: (1) a single antimutagen (e.g., retinol)
      tested in combination with various mutagens or (2) antimutagens tested against a
      single mutagen (e.g., aflatoxin B1). Data are presented in the profiles showing a
      dose range for a given antimutagen and a single dose for the corresponding
      mutagen; inhibition as well as enhancement of mutagenic activity is indicated.
      Information was found in the literature on the testing of selected combinations
      of 16 retinoids and carotenoids vs. 33 mutagens. Of 528 possible antimutagen
      mutagen combinations, only 82 (16%) have been evaluated. The most completely
      evaluated retinoids are retinol (28 mutagens), retinoic acid and retinol acetate
      (7 mutagens each), and retinal and retinol palmitate (6 mutagens each). beta
      Carotene is the most frequently tested carotenoid (15 mutagens). Of the remaining
      retinoids and carotenoids, 8 were evaluated in combination with a single mutagen
      and the other 2 were tested against only 2 or 3 mutagens. Most of the data on
      antimutagenicity in vitro are available for S. typhimurium strains TA98 and
      TA100. Substantial data also are available for sister-chromatid exchanges in
      vitro and chromosome aberrations in vitro and in vivo. This report emphasizes the
      metabolic as well as the antimutagenic effects of retinoids in vitro and in vivo.

PMID- 1376419
TI  - The analysis of the joint effect of substances on reversion systems and the
      assessment of antimutagenicity.
AB  - The statistical methods for the analysis of mutagenicity and carcinogenicity
      underwent considerable theoretical-practical development following the need for
      assessing the mutagenic and carcinogenic potential of substances.
      Antimutagenicity is investigated through the analysis of respondents in dose
      response assays, when two different molecules are administered separately and as
      a mixture to a respondent system. When the number of respondent units is high,
      and doses are orthogonal, it is possible to apply simple models such as analysis
      of variance. This is not always possible or common, and alternative approaches
      have been developed, based on multiple regression and on tables of proportions.
      In this work, some of the most frequently used methods for the assessment of
      joint responses are reviewed, particularly those based on multiple regression,
      such as the method of Shaeffer et al. and the method of Hass et al. In order to
      illustrate these methods, joint responses of perylene and cyclopentapyrene, of N
      acetylcysteine and dinitropyrene, and of N-acetylcysteine and extracts from
      diesel exhausts were analyzed. An antagonistic effect of perylene on the action
      of CPP was detected by the algorithm of Shaeffer et al. The effect is not
      multiplicative, i.e., it is not proportional to the product of doses. The
      antimutagenic effect of N-acetylcysteine on dinitropyrene is multiplicative, as
      detected by the method of Hass et al. The latter reveals that the inhibition by N
      acetylcysteine on the mutagenic effect of extracts from diesel exhausts is also
      multiplicative.

PMID- 1376420
TI  - Modulation of the mutagenic response in prokaryotes.
AB  - Short-term tests investigating genetic end-points in prokaryotes have been
      extensively used worldwide not only for risk assessment purposes but also for
      evaluating the modulation of the mutagenic response. In spite of some intrinsic
      limitations, such as the lack of cell compartmentalization or the need for an
      exogenous metabolic system working extracellularly, experimental systems in
      bacteria can provide useful preliminary indications and some information on the
      mechanisms involved. In the large majority of studies the putative modulator is
      mixed with a known mutagen and then assayed in target bacteria, with suitable
      controls. However, under natural conditions exposure of target cells to
      modulators may either precede, co-exist with, or follow exposure to mutagens.
      Therefore, a variety of methodological variations, involving pre-treatment, co
      treatment, or post-treatment of bacteria with the putative modulator, have been
      designed. Application of these procedures showed that the effects of modulators
      can be completely upset, from inhibition to enhancement, or vice versa, by
      changing the experimental conditions. Use of methodological variations may
      provide more complete information on the spectrum of possible effects in bacteria
      as well as a better insight into modulation mechanisms. Several examples
      illustrating the flexibility of the Salmonella test in this field of research are
      available. On the other hand, the widespread use of these relatively simple
      techniques, yet requiring skillfulness and experience, may lead to some misuse or
      oversimplifications. A rather common inadequacy is to use excessive amounts of
      test mutagens, or to express the results in terms of revertants/survivors, rather
      than revertants/plate. In fact, in the Salmonella test the number of revertants
      is rather unrelated to the initial number of plated bacteria, provided a normal
      background lawn of bacterial growth is formed. Thus, a 50% killing of bacteria
      will not appreciably influence the number of revertants/plate, but expressed as
      revertants/survivors the effect will look twice as large.

PMID- 1376422
TI  - Antimutagenicity in cultured mammalian cells.

PMID- 1376421
TI  - Antimutagenicity in yeast.
AB  - In recent years there has been increasing interest in antimutagenesis, and
      studies have been done using both prokaryotic and eukaryotic systems. In
      eukaryotic systems the first studies were performed with different strains of
      Schizosaccharomyces pombe. In particular, caffeine and L-methionine were
      investigated. Different strains of Saccharomyces cerevisiae were employed in
      studies of a wide variety of compounds, including acridine, saccharin, salts,
      tumor promoters and co-carcinogens. Strain D7 was widely employed and
      antimutagenic activity of spermine, chlorophyllin, cobaltous chloride and
      fermented milk is reported.

PMID- 1376423
TI  - Anticlastogenicity in cultured mammalian cells.
AB  - Basic and applied research on anticlastogenicity has not only revealed valuable
      evidence on the mechanisms governing the induction of chromosomal aberrations by
      environmental mutagens, but also contributed effective ideas on a practical
      employment of this knowledge for the protection of individuals at risk.
      Considering the basic role played by chromosomal anomalies in oncogenesis,
      additional weight must be attributed to studies on anticlastogenicity. The
      employment of human cells in this kind of study dates back to 1969/70, while
      classical mammalian cell systems were used only later on. Various modes of
      application of both clastogens and anticlastogens (AC) were examined, but
      simultaneous addition to the cultures of both reagents was the most favored way.
      A wide spectrum of cytogenetic endpoints can be studied, but differences can be
      demonstrated with regard to efficacy of inhibitors on different types of
      cytogenetic changes, e.g., open breaks vs. rearrangements, but also vs. SCEs.
      Depending on their mode of influence on this spectrum, ACs can be arranged in
      various categories which are of practical importance, for instance, with regard
      to their oncogenic potential. A wide variety of factors was shown to influence AC
      action, e.g., time and mode of application of the test substances, physiologic
      and metabolic features of the cell types studied, type and mechanism of the
      clastogen used, etc. The addition of S9 mix can drastically change the patterns
      of efficacy of the ACs. The combined application of two or more ACs, as far as
      investigated, apparently neither potentiates nor even merely adds their effects.

PMID- 1376424
TI  - Modulation of genotoxicity in Drosophila.
AB  - The extensive knowledge of the genetics of Drosophila melanogaster and the long
      experimental experience with this organism have made it of unique usefulness in
      mutation research and genetic toxicology. The development of somatic mutation and
      recombination tests (SMART) has provided sensitive, rapid and cheap assays for
      investigations of mutagenic and recombinogenic properties of chemicals. The
      present paper deals with the SMART wing spot assay, developed by Graf et al.
      (1984). The use of two genetic markers, multiple wing hair (mwh) and flare (flr)
      in the third chromosome, makes it possible to discern localized recombinogenic
      effects on the two intervals--the major, euchromatic, part of the chromosome, and
      the mostly heterochromatic centromere region. The distribution of induced mitotic
      recombination varied between test chemicals. Ethylene oxide caused a specific
      increase of twin spots, indicating a localized induction of somatic recombination
      in the centromere region. The wing spot assay has turned out to be suitable for
      combined treatment with chemicals in order to study antimutagenic and other
      modulating effects by mutagenic and recombinogenic chemicals. Examples of the use
      of this assay for such a purpose are presented in this paper. The inhibitor of
      poly ADP-ribosylation, 3-aminobenzamide (3AB), caused a pronounced increase of
      wing spots, induced by alkylating agents. The data indicate that this interaction
      between alkylating agents and 3AB is solely due to an effect on somatic
      recombination but not on point mutations. The inhibitor of topoisomerases,
      novobiocin, which presumably acts on the chromatin configuration, had different
      modulating effects on spots induced by methyl methanesulfonate (MMS) and
      ethylnitrosourea (ENU). Novobiocin essentially acted as an antirecombinogenic
      agent in cotreatment experiments with MMS and as antimutagenic agent with ENU.
      Attempts to interfere with mutagenic and recombinogenic effects of the radical
      generating agents bleomycin, menadione and paraquat, by agents acting on the
      defence mechanisms against oxygen radicals, were essentially unsuccessful.

PMID- 1376425
TI  - Antimutagenicity of secondary metabolites from higher plants.
AB  - Higher plants contain both mutagens and antimutagens and are susceptible to
      mutagenesis but screening programs for detection of antimutagenesis rarely employ
      higher plant systems. Short-term bacterial and mammalian tissue culture systems
      are the norm. Using modified screening tests for detecting antimutagenic agents,
      higher plants have been shown to contain a variety of structurally novel
      antimutagenic agents. Systematic bioassay-directed methodology resulted in the
      isolation in pure form and biological and chemical characterization of the
      responsible individual active components from various plants. The methodology in
      use is illustrated by the isolation of cinnamic acid, cinnamyl cinnamate and
      cinnamyl ricinoleate as the active constituents of the classic medicinal plant
      product, Styrax asiatica. The methods which may be used to reveal structure
      activity relationships and to explore putative molecular modes of action are
      illustrated with excerpts from the same study.

PMID- 1376426
TI  - Anticarcinogenesis in fish.
AB  - Rainbow trout respond to a range of natural and synthetic dietary tumor
      modulators. Observed modulations of final tumor incidence include inhibition,
      promotion and cocarcinogenesis, depending on modulator, carcinogen, target organ,
      and relative order of carcinogen and modulator exposure. Despite several obvious
      limitations (e.g. lung, colon, mammary gland, bladder are not available as target
      organs), the trout model possesses several important features that have made it
      valuable for tumor modulation studies. (1) The comparative advantage. Since
      rodents are not perfect human surrogates, studies with alternative vertebrates
      such as trout have provided important comparative mechanism information for
      confident extrapolation of animal studies to humans. For example, beta
      naphthoflavone appears to inhibit aflatoxin B1 hepatocarcinogenicity by species
      independent mechanisms that readily extrapolate to humans. By contrast other
      modulators, including butylated hydroxyanisole, inhibit aflatoxin B1
      hepatocarcinogenesis in rats by an enabling mechanism shown to be absent in
      trout, namely the induction of an aflatoxin B1-specific glutathione S-transferase
      isozyme. Interestingly, evidence is presently lacking that this determinant
      mechanism would be operative in humans. (2) The sensitivity advantage. Trout
      sensitivity and small body size at exposure have permitted tumor studies with
      carcinogens and HPLC-purified anticarcinogen intermediates too scarce to study in
      rodents. (3) The low cost advantage. The very low cost of trout tumor studies has
      enabled statistically challenging issues in molecular dosimetry, dose-response,
      and risk-benefit analysis to be addressed using as many as 9600 animals per tumor
      study at modest budget. In particular, these designs provide modulator-mediated
      alterations in precisely determined carcinogen TD50 values, rather than changes
      in simple tumor incidence, to quantify more rigorously modulator potencies for
      tumor inhibition or promotion as a function of dietary concentrations.

PMID- 1376427
TI  - Screening for chemopreventive (anticarcinogenic) compounds in rodents.
AB  - The Chemoprevention Branch is testing dozens of candidate chemopreventive
      compounds in the following rodent model carcinogenesis systems: mouse skin
      papillomas, DMBA/TPA induced, rat mammary adenocarcinoma, DMBA and MNU induced,
      hamster tracheal squamous cell carcinoma, MNU induced, and lung adenocarcinoma,
      DEN induced, rat and mouse colon adenocarcinoma, AOM and MAM acetate induced,
      respectively, and mouse bladder carcinoma, hydroxy BBN induced. Significant
      chemopreventive (i.e., anticancer) effects have been produced with 4-hydroxy
      phenylretinamide, difluoromethylornithine, piroxicam, oltipraz (a dithiolthione),
      calcium glucarate, N-acetylcysteine, beta-carotene, ibuprofen,
      dehydroepiandrosterone (DHEA) and a 16-fluoro DHEA analog, 8354, tamoxifen,
      glycyrrhetinic acid, molybdate, selenite, curcumin, and fumaric acid.

PMID- 1376428
TI  - Antimutagenic effects in humans.
AB  - The application of antimutagenicity studies to human somatic mutation is
      discussed, with emphasis on the potential for future studies. Five assay-gene
      combinations are now available for measuring human somatic mutation in
      lymphocytes and erythrocytes. Results with these combinations have defined the
      human background levels, and show clear responses of mutant frequency to a
      variety of mutagens. The testing of antimutagenic effects on background
      frequencies is feasible, but has not yet been done. The major uncertainty in such
      studies is the unknown age of mutant cells in the background, since only the
      newly forming mutants are potentially susceptible to most antimutagenic
      treatments. Intervention studies in the face of active mutagenicity and the use
      of other genotoxicity endpoints, such as chromosome aberrations, micronuclei and
      DNA adducts, are considered briefly.

PMID- 1376429
TI  - The use of the micronucleus test on exfoliated cells to identify anti-clastogenic
      action in humans: a biological marker for the efficacy of chemopreventive agents.
AB  - Laboratory and epidemiological studies support the hypothesis that cancer
      incidence in human populations can be reduced by supplementing high-risk
      individuals with chemopreventive agents. Many candidate agents have been
      identified, too many to be assayed in long-term clinical trials. As an alternate
      approach, intermediate markers are currently being evaluated as short-term
      screens for the activity of chemopreventive agents in humans. These markers
      quantify cellular and molecular changes of biological significance to the process
      of carcinogenesis. One such marker is the micronucleus test on exfoliated cells.
      This assay has been used to quantify chromosomal breakage occurring in the human
      oral cavity, esophagus, cervix, lung, nasal cavity and urinary bladder.
      Intervention trials on high-risk populations have shown that supplementation with
      chemopreventive agents can modulate this breakage. This article will review the
      evidence in support of the use of this assay as a biological marker for the
      efficacy of a chemopreventive regime. Basic problem areas in the design and
      conduct of this assay in humans will also be discussed, as will the future
      potential of the assay.

PMID- 1376430
TI  - Urinary biomarkers and the rate of DNA damage in carcinogenesis and
      anticarcinogenesis.
AB  - Endogenous oxidative processes are shown to generate hydrogen peroxide and .OH
      radicals, which react in vivo to form a variety of products. Thymidine glycol
      (Tg) and 8-hydroxydeoxyguanosine (8-dRG-OH) are such products. They result from
      the excision repair of DNA and are excreted in urine. Both products can be used
      as biomarkers in the dosimetry of oxidative damage to DNA. Since oxidative
      processes and accumulation of their effects contribute to carcinogenesis, the
      proposed rate-of-damage hypothesis provides a rationale for using these
      biomarkers in early diagnostics and in the assessment of carcinogenic and
      anticarcinogenic properties of diets, foods, and food components, as well as
      certain exogenous toxicants and agents. Approaches for measurement of urinary
      biomarkers of DNA damage are reviewed.

PMID- 1376431
TI  - Chemoprevention clinical trials.
AB  - As part of a program to develop drugs which will delay or prevent cancer in
      humans, the Chemoprevention Branch, National Cancer Institute, National
      Institutes of Health, is sponsoring 12 Phase I and 22 Phase II and III clinical
      trials. Three agent classes are significantly advanced in the trials. These are
      the retinoids, including 13-cis-retinoic acid, retinol, and 4
      hydroxyphenylretinamide (nine studies), beta-carotene (seven studies), and
      calcium compounds (three studies). In addition, six promising new compounds are
      in Phase I or Phase II trials. These are: piroxicam, ibuprofen, oltipraz (a
      dithiolthione), difluoromethylornithine, glycyrrhetinic acid, and N
      acetylcysteine. Key concepts related to the development of cancer chemopreventive
      agents are (1) the need for long-term administration, (2) the need for oral route
      of administration, (3) the matching of toxic side effects to degree of cancer
      risk.

PMID- 1376432
TI  - Workshop on DNA repair.
AB  - A workshop on DNA repair with emphasis on eukaryotic systems was held, under the
      auspices of the EC Concerted Action on DNA Repair and Cancer, at Noordwijkerhout
      (The Netherlands) 14-19 April 1991. The local organization of the meeting was
      done under the auspices of the Medical Genetic Centre South-West, The Netherlands
      (MGC), c/o Department of Radiation Genetics and Chemical Mutagenesis, University
      of Leiden (The Netherlands). Local organizers were: D. Bootsma (chairman), W.
      Ferro, J.H.J. Hoeijmakers, A.R. Lehmann, P.H.M. Lohman, L. Mullenders, and A.A.
      van Zeeland (secretarial assistance: Mrs. C. Escher-van Heerden and Mrs. R.
      Bontre). Over 190 scientists participated, and the format of the meeting followed
      that of the 1987 workshop on the 'Molecular Aspects of DNA Repair' (Friedberg et
      al., 1987). Plenary review talks in the mornings were followed, in the afternoon,
      by poster viewing in three or four parallel sessions. Groups of 15-20 posters
      were discussed in detail, and later on, in plenary sessions, chairpersons of the
      poster discussions reviewed the afternoons' posters. The principal themes of the
      meeting were the isolation and characterisation of repair genes and proteins,
      repair in specific sequences, consequences of defective DNA repair, and new
      methods for detecting DNA damage and repair. Remarkable progress has been made
      recently in all of these areas, and many exciting new results were presented. It
      is impossible to summarize all contributions to this (intensive) one-week
      meeting. Therefore, and for the sake of coherence, presentations that did not fit
      easily into any of the general themes of the meetings have not been included.

PMID- 1376433
TI  - Differences in nucleotide and base DNA excision repair observed during mitogenic
      stimulation of bovine lymphocytes.
AB  - The bromodeoxyuridine density-shift technique was used to examine nucleotide and
      base DNA excision repair in quiescent and lectin stimulated bovine lymphocytes
      damaged with either ultraviolet light or dimethyl sulfate (DMS). Compared to a
      number of human cell lines, quiescent lymphocytes were less proficient in the
      repair of both types of damage. Repair replication was enhanced upon mitogenic
      stimulation, but both the amount and time course of the increase in repair
      depended upon the damaging agent used. A 2-3-fold increase in UV light induced
      repair replication occurred early during stimulation and subsided only gradually
      as stimulation proceeded. However, the profile of DMS induced repair increased 7
      fold and then decreased, in parallel with measurements of lectin-stimulated DNA
      replication. Estimates of average repair patch sizes showed that quiescent
      lymphocytes produced smaller patches of 7 nucleotides in response to DMS damage
      while UV light irradiation resulted in repair patches of 20 nucleotides. During
      stimulation, patch sizes appeared to increase to maximum values of 45 and 33
      nucleotides in response to UV light and DMS, respectively, one day prior to the
      peak of DNA replication. These increases in patch size were followed by a gradual
      decrease towards unstimulated levels. However, the appearance of a DNA species of
      intermediate density in the gradient profiles made the interpretation of repair
      patch sizes in stimulated cells difficult. These results are discussed as
      evidence not only for differences in the mechanisms of nucleotide and base
      excision repair but also for changes in repair as the cell progresses through the
      cell cycle.

PMID- 1376434
TI  - UV endonuclease-mediated enhancement of UV survival in Micrococcus luteus:
      evidence revealed by deficiency in the Uvr homolog.
AB  - Unlike its phage T4 counterpart (also known as endonuclease V), Micrococcus
      luteus UV endonuclease (pyrimidine dimer DNA glycosylase/apurinic-apyrimidinic
      endonuclease) has suffered from lack of genetic evidence to implicate it in the
      promotion of UV survival of the cell, i.e., mutants with its deficiency are no
      more UV-sensitive than the wild type. On the assumption that the contribution of
      UV endonuclease is obscured by the presence of a homolog of Escherichia coli
      UvrABC endonuclease, which has recently been identified in this bacterium,
      survival studies were carried out in its absence. With 254-nm UV irradiation,
      which generates not only pyrimidine dimers but also 6-4 photoproducts as lethal
      lesions, a double mutant defective in both UV endonuclease and the Uvr homolog
      was shown to be more sensitive than a single mutant defective only in the latter,
      with a dose reduction factor of approximately 2 at the survival level of 37%.
      Furthermore, molecular photosensitization, which produces only pyrimidine dimers,
      revealed an even greater difference in sensitivity, the dose reduction factor
      being about 3.4. These results indicate that the contribution to cell survival of
      UV endonuclease, an enzyme specific for pyrimidine dimers, is manifest if the
      backup by the Uvr homolog is absent.

PMID- 1376435
TI  - Biochemical heterogeneity in xeroderma pigmentosum complementation group E.
AB  - Cells from two patients with xeroderma pigmentosum complementation group E (XP-E)
      have been shown to lack an activity which binds specifically to UV-irradiated DNA
      (Chu and Chang, 1988). We investigated the occurrence of this binding activity in
      cell strains from nine additional, unrelated XP-E patients and found that all but
      one of these strains contained normal levels of the binding protein. Furthermore,
      the binding activity from these XP-E strains was indistinguishable from that of
      normal controls in thermal stability, behavior on ion-exchange chromatography,
      and electrophoretic mobility of protein-DNA complexes, indicating that there were
      no gross structural alterations in the protein. The association of XP-E with a
      deficiency in DNA-damage binding protein in cells from 3 of 12 XP-E patients
      (compared to 0 of 20 non-XP-E controls) is statistically significant (p less than
      0.05), but there is no obvious correlation between the biochemical defect and the
      clinical or cellular characteristics of individual patients. Implications of
      these findings for the role of the binding protein in XP-E are discussed.

PMID- 1376436
TI  - Defective DNA endonuclease activities in Fanconi's anemia cells, complementation
      groups A and B.
AB  - Cells from patients with the inherited disorder, Fanconi's anemia (FA), were
      analyzed for endonucleases which recognize DNA interstrand cross-links and
      monoadducts produced by psoralen plus UVA irradiation. Two chromatin-associated
      DNA endonuclease activities, defective in their ability to incise DNA-containing
      adducts produced by psoralen plus UVA light, have been identified and isolated in
      nuclei of FA cells. In FA complementation group A (FA-A) cells, one endonuclease
      activity, pI 4.6, which recognizes psoralen intercalation and interstrand cross
      links, has 25% of the activity of the normal human endonuclease, pI 4.6, on 8
      methoxypsoralen (8-MOP) plus UVA-damaged DNA. In FA complementation group B (FA
      B) cells, a second endonuclease activity, pI 7.6, which recognizes psoralen
      monoadducts, has 50% and 55% of the activity, respectively, of the corresponding
      normal endonuclease on 8-MOP or angelicin plus UVA-damaged DNA. Kinetic analysis
      reveals that both the FA-A endonuclease activity, pI 4.6, and the FA-B
      endonuclease activity, pI 7.6, have decreased affinity for psoralen plus UVA
      damaged DNA. Both the normal and FA endonucleases showed approximately a 2.5-fold
      increase in activity on psoralen plus UVA-damaged reconstituted nucleosomal DNA
      compared to damaged non-nucleosomal DNA, indicating that interaction of these FA
      endonucleases with nucleosomal DNA is not impaired. These deficiencies in two
      nuclear DNA endonuclease activities from FA-A and FA-B cells correlate with
      decreased levels of unscheduled DNA synthesis (UDS), in response to 8-MOP or
      angelicin plus UVA irradiation, in these cells in culture.

PMID- 1376437
TI  - (6-4) photoproducts and not cyclobutane pyrimidine dimers are the main UV-induced
      mutagenic lesions in Chinese hamster cells.
AB  - A partial revertant (RH1-26) of the UV-sensitive Chinese hamster V79 cell mutant
      V-H1 (complementation group 2) was isolated and characterized. It was used to
      analyze the mutagenic potency of the 2 major UV-induced lesions, cyclobutane
      pyrimidine dimers and (6-4) photoproducts. Both V-H1 and RH1-26 did not repair
      pyrimidine dimers measured in the genome overall as well as in the active hprt
      gene. Repair of (6-4) photoproducts from the genome overall was slower in V-H1
      than in wild-type V79 cells, but was restored to normal in RH1-26. Although V-H1
      cells have a 7-fold enhanced mutagenicity, RH1-26 cells, despite the absence of
      pyrimidine dimer repair, have a slightly lower level of UV-induced mutagenesis
      than observed in wild-type V79 cells. The molecular nature of hprt mutations and
      the DNA-strand specificity were similar in V79 and RH1-26 cells but different
      from that of V-H1 cells. Since in RH1-26 as well as in V79 cells most hprt
      mutations were induced by lesions in the non-transcribed DNA strand, in contrast
      to the transcribed DNA strand in V-H1, the observed mutation-strand bias suggests
      that normally (6-4) photoproducts are preferentially repaired in the transcribed
      DNA strand. The dramatic influence of the impaired (6-4) photoproduct repair in V
      H1 on UV-induced mutability and the molecular nature of hprt mutations indicate
      that the (6-4) photoproduct is the main UV-induced mutagenic lesion.

PMID- 1376438
TI  - Identification of cellular factors that recognize UV-damaged DNA in Drosophila
      melanogaster.
AB  - Using a gel electrophoresis DNA band-shift assay, we have identified 2 DNA
      binding protein complexes in wild-type Drosophila embryonic cells which have high
      affinity for UV-irradiated, double-stranded DNA. Screening of Drosophila mutants
      deficient in DNA repair led to the identification of 5 mutants which lacked
      either one of the 2 protein complexes. Four excision repair-deficient mutants
      (mus-201, phr, mus-308 and mus-205) lacked one protein complex (Factor 2). The
      other protein complex (Factor 1) was not detectable in the post-replication
      repair-deficient mutant mus-104. These findings might suggest the possible
      involvement of these gene products in lesion recognition and repair of UV-induced
      photoproducts in DNA.

PMID- 1376439
TI  - Genetic toxicology of propylene oxide and trichloropropylene oxide--a review.
AB  - Aliphatic epoxides are a group of compounds extensively used in industry and as
      laboratory reagents, and can be produced as metabolic intermediates. An important
      aliphatic epoxide is propylene oxide, extensively used in the production of
      propylene glycol and polyols used in the manufacture of polyurethane polymers.
      The widespread human exposure to propylene oxide is of great health concern. In
      this review an attempt has been made to evaluate and update the genotoxic effects
      of propylene oxide and trichloropropylene oxide based on the available
      literature.

PMID- 1376440
TI  - Statistical methods for short-term tests in genetic toxicology: the first fifteen
      years.
AB  - Short-term tests (STTs) for detecting and assessing genotoxic or mutagenic
      effects have catalyzed the development of biostatistical methods for more than
      one decade. Most notably, the Ames Salmonella/microsome assay created statistical
      methodology with a range of applications going beyond genotoxicity. Early
      approaches with parametric statistical methods appeared to be insufficient and
      have been replaced by non-parametric ones requiring less restrictive
      distributional assumptions. There have also been successful attempts to use
      biomathematical models for establishing dose-response relationships.
      Overdispersion has been recognized as a major problem for the evaluation of
      mutagenic count data and methods to cope with it have became available. A theory
      of generalized linear modelling is emerging to combine dose-response modeling
      with much less restrictive distributional assumptions, while allowing the
      inclusion of concomitant factors arising from the experimental conditions. The
      methodological survey below reviews the present state of this development and is
      intended to promote further research into biostatistical issues and methods of
      analysis. Appropriate methods for the design and analysis of STTs are discussed.
      The progress for the Ames assay was only partially transmitted to the analysis of
      the large number of other short-term assays. Several such assays are reviewed
      with respect to their present state of statistical evaluation.

PMID- 1376441
TI  - DNA adduct formation by 12 chemicals with populations potentially suitable for
      molecular epidemiological studies.
AB  - DNA adduct formation, route of absorption, metabolism and chemistry of 12
      hazardous chemicals are reviewed. Methods for adduct detection are also reviewed
      and approaches to sensitivity and specificity are identified. The selection of
      these 12 chemicals from the Environmental Protection Agency list of genotoxic
      chemicals was based on the availability of information and on the availability of
      populations potentially suitable for molecular epidemiological study. The 12
      chemicals include ethylene oxide, styrene, vinyl chloride, epichlorohydrin,
      propylene oxide, 4,4'-methylenebis-2-chloroaniline, benzidine, benzidine dyes
      (Direct Blue 6, Direct Black 38 and Direct Brown 95), acrylonitrile and benzyl
      chloride. While some of these chemicals (styrene and benzyl chloride, possibly
      Direct Blue 6) give rise to unique DNA adducts, others do not. Potentially
      confounding factors include mixed exposures in the work place, as well the
      formation of common DNA adducts. Additional research needs are identified.

PMID- 1376442
TI  - Granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor (2).

PMID- 1376443
TI  - [Lead poisoning in children].

PMID- 1376444
TI  - CD5+ B lymphocytes and other lymphocyte subsets in primary Sjogren's syndrome.
AB  - CD5+ B cells and other lymphocyte subsets were analyzed by flow cytometry in
      patients with primary Sjogren's syndrome (pSS), in healthy subjects (HS) and in
      patients with various control diseases. When compared with HS, patients with pSS
      were found to have similar levels of CD5+ B cells and decreased levels of CD8+ T
      cells (P = 0.0003). When compared with patients with various other diseases,
      however, the number of CD5+ B cells in pSS was more than twice as high (P =
      0.0002), whereas no difference was found between numbers of CD8+ T cells. When
      the number of CD5+ B cells was expressed as a percentage of total B cells, the
      results obtained were similar to those with absolute numbers. Determination of
      lymphocyte subsets may be used as a diagnostic aid for Sjogren's syndrome in
      selected patients with suspected immunological diseases of unknown type.

PMID- 1376446
TI  - Two brothers with a variant of hereditary sensory neuropathy.
AB  - We report two brothers with the clinical symptoms and neuropathological findings
      of hereditary sensory and autonomic neuropathy (HSAN) type IV but with normal
      sweating function and absence of recurrent fever. We propose that our patients
      may have a lower degree of expression of the genetic defect underlying HSAN type
      IV or that they represent a separate genetic entity.

PMID- 1376445
TI  - Monoamine metabolites, iron induced seizures, and the anticonvulsant effect of
      tannins.
AB  - Intracortical injections of iron ions have been shown to induce recurrent
      seizures and epileptic discharges in the EEG. (-)-Epigallocatechin (EGC) and (-)
      epigallocatechin-3-O-gallate (EGCG), isolated from green tea leaves, have been
      reported to prevent or diminish the occurrence of epileptic discharges induced by
      iron ions, and to inhibit catechol-O-methyltransferase. Iron ions significantly
      increased DOPAC and HVA levels in the intrastriatal perfusate 140 and 180
      minutes, respectively, after injection. EGC and EGCG inhibited the increases
      induced by iron ions. Furthermore, EGCG decreased the HVA level in the perfusate
      200 minutes after injection whether or not iron ions were injected. Iron ions had
      no effect on the 5-HIAA level, and EGC and EGCG raised it. These results suggest
      that formation of an epileptic focus induced by iron ions might be accompanied by
      activation of dopaminergic neurons, and that EGC and EGCG inhibit that
      hyperactivity.

PMID- 1376447
TI  - Acquisition of signs from American sign language in hearing individuals following
      left hemisphere damage and aphasia.
AB  - Three severely aphasic hearing patients with no prior knowledge of sign language
      were able to acquire competency in aspects of American Sign Language (ASL)
      lexicon and finger spelling, in contrast to a near complete inability to speak
      the English counterparts of these visuo-gestural signs. Two patients with damage
      in left postero-lateral temporal and inferior parietal cortices mastered
      production and comprehension of single signs and short meaningful sign sequences,
      but the one patient with damage to virtually all left temporal cortices was less
      accurate in single sign processing and was unable to produce sequences of signs
      at all. These findings suggest that conceptual knowledge is represented
      independently of the auditory-vocal records for the corresponding lexical
      entries, and that left anterior temporal cortices outside of traditional
      "language areas" are part of the neural network which supports the linkage
      between conceptual knowledge and linguistic signs, especially as they are used in
      the sequenced activations required for production or comprehension of meaningful
      sentences.

PMID- 1376448
TI  - Overproduction of voltage-dependent Na+ channels in the developing brain of
      genetically seizure-susceptible E1 mice.
AB  - We used E1 mice, a ddY mouse-derived, autosomal mutant strain and a model of
      hereditary sensory-precipitated epilepsy, to test the hypothesis that epileptic
      susceptibility may be associated with the activity of voltage-dependent ion
      channels. We examined the saxitoxin binding capacity of the receptor site 1 of
      the Na+ channel alpha-subunit, the expression activity of the Na+ channel mRNA,
      the veratridine-induced 22Na+ influx in the brain synaptosomes, and the regional
      distribution of Na+ channels in the brain. Compared with control ddY mice, in E1
      mice which have not experienced seizures, the number of Na+ channels in the brain
      synaptosomes increased by approximately 20% starting at the fourth postnatal week
      through the adult stage as determined by [3H]saxitoxin binding assay. Northern
      blot hybridization analysis showed excess expression of Na+ channel mRNA (by 30
      40%) coincidentally with Na+ channel increases. Regional analysis using the
      saxitoxin binding assay demonstrated approximately 1.3-fold denser distribution
      of Na+ channels in the cortex and cerebellum but not the hippocampus and midbrain
      including thalamus of E1 mice compared to ddY mice. Scatchard plot analysis for
      saxitoxin binding in the cortex of E1 mouse brains revealed higher maximum
      binding capacity (Bmax) values (ddY, 4.43 +/- 0.28 pmol/mg protein; E1, 5.43 +/-
      0.25 pmol/mg protein) without a change in Kd (ddY, 1.05 +/- 0.03 nM; E1, 1.03 +/-
      0.01 nM). Lastly, veratridine-evoked 22Na+ influx, sensitive to tetrodotoxin, was
      increased approximately 45% in the cortical synaptosomes in six-week-old E1
      mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376449
TI  - Neurons of origin of zinc-containing pathways and the distribution of zinc
      containing boutons in the hippocampal region of the rat.
AB  - Recent methods allow the study of neurons that contain zinc in synaptic vesicles
      of their boutons (Timm-stainable boutons) by the intravital precipitation (local
      or throughout the CNS) of the vesicular zinc with selenium compounds and its
      subsequent retrograde transport to the parent neurons, where the precipitate can
      be silver enhanced. The present study is a description of the distribution of
      zinc-containing neurons, their possible connections and their terminal fields
      within the hippocampal region of the rat. Problems inherent to the methods are
      addressed. Finally, based on the results and a review of literature, the possible
      function of zinc in the hippocampal region is considered. Neurons which contain
      silver-enhanced precipitates were observed in layers II, V and VI of the lateral
      entorhinal area and in layers V and VI of the medial entorhinal area. In the
      parasubiculum, labeled cells were seen in layer II/III of the parasubiculum a and
      in layer V. Labeled cells in the presubiculum were concentrated in layers III and
      V, in the hippocampal pyramidal cell layer and the dentate granule cell layer,
      but neurons containing precipitates were largely absent from the subiculum. Zinc
      containing axonal boutons defined subpopulations within principal hippocampal
      neuron populations. Within layer II of the lateral entorhinal cortex and the
      pyramidal cell layer for regio inferior deeply situated neurons were labeled,
      whereas superficially placed pyramidal cells were labeled in regio superior. The
      neuropil staining described in the present study corresponded to that found in
      earlier studies. However, glial and vascular staining or unspecific background
      were largely absent, and the neuropil staining could unequivocally be identified
      light microscopically. Methodological problems are most prominently reflected in
      unstained mossy fibers in some animals. Based on series from animals treated with
      decreasing doses of sodium selenite and increased survival times, this problem
      can be related to small amounts of circulating reactive selenium and a
      competition of zinc compartments (vesicles) for the selenium. Staining will fail
      where the competition prevents individual compartments from reaching a threshold
      amount of zinc precipitate for silver amplification. A guide to evaluate
      histological material is provided. The distribution of zinc-containing boutons
      and their cells of origin indicate that zinc-containing and zinc-negative
      projections are not organized as parallel pathways. The mossy fibers provide an
      example of a pure zinc-containing pathway. Projections from regio superior to the
      dorsal presubiculum are likely to be zinc-negative while projections from the
      same area to the subiculum are zinc-containing.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1376450
TI  - Intracellular responses of olfactory bulb granule cells to stimulating the
      horizontal diagonal band nucleus.
AB  - The effects of centrifugal afferents on membrane potentials of identified granule
      cell layer using evoked field potential profiles, and trans-synaptic activation
      via antidromic stimulation of output cell axon collaterals. Intracellular
      recordings maintained for 4-30 min showed complex spontaneous spike discharges
      and allowed characterization of the cell's input resistance, and on some
      occasions its morphology following intracellular injection of Lucifer Yellow.
      Stimulation in the nucleus of the horizontal limb of the diagonal band, but not
      surrounding regions, produced hyperpolarizing responses in 13 of 27 cells in the
      granule cell layer; four of these were morphologically identified as granule
      cells of two types, in five the responses had reversal potentials more negative
      than the resting potential, and six were identified as granule cells by
      monosynaptic activation from output axon collaterals. A different set of three
      cells in the granule cell layer responded with depolarization. The results are
      consistent with the inhibition of tonic activity of granule cells by the nucleus
      of the horizontal limb of the diagonal band, leading to disinhibition of mitral
      and tufted cells via dendrodendritic synapses of granule cells on mitral/tufted
      cell secondary dendrites.

PMID- 1376451
TI  - Intravenous injection of Evans Blue labels magnocellular neuroendocrine cells of
      the rat supraoptic nucleus in situ and after dissociation.
AB  - Previous work has demonstrated that intravenous injection of neuronal tracers,
      e.g. horseradish peroxidase or Fast Blue, can retrogradely label neurons in brain
      areas that project outside the blood-brain barrier, e.g. magnocellular
      neuroendocrine neurons of the hypothalamus. Here we have shown that 24 h after
      intravenous injection of the fluorescent retrograde tracer Evans Blue, the same
      population of magnocellular neuroendocrine neurons is labeled in the
      paraventricular, supraoptic and accessory magnocellular nuclei. Parvicellular
      neuroendocrine cells in the paraventricular nuclei are also labeled. Most Evans
      Blue-labeled magnocellular neuroendocrine cells in the supraoptic nucleus could
      be stained immunocytochemically for neurophysins, suggesting that these neurons
      continue to produce their peptide hormones after taking up the fluorescent dye.
      Ultrastructural observation of supraoptic cells retrogradely labeled with Evans
      Blue shows that 95% of the neurons appeared healthy. There was no ultrastructural
      evidence of degeneration, hyperstimulation, or interruption of the axoplasmic
      flow. Labeling the neuroendocrine cells with Evans Blue did not alter the size of
      magnocellular cells, the animal's fluid balance or ingestive behavior. Following
      enzymatic/mechanical dissociation of the supraoptic nucleus from animals that had
      been injected with Evans Blue 24 h previously, phase-bright neurons that often
      contained fluorescent material were observed, thus identifying these neurons as
      neuroendocrine. Recording from identified neuroendocrine cells showed that these
      neurons generated spontaneous or current-evoked overshooting action potentials
      with an afterhyperpolarization and had negative resting membrane potentials.
      Action potential broadening, a feature of magnocellular neurons, was observed
      during bursts of action potentials elicited by depolarizing current injection.
      Taken together, this work would suggest that Evans Blue is non-toxic at the doses
      used and that it provides a method to identify single neuroendocrine cells in
      primary cell cultures made from adult hypothalamus for voltage-clamp recordings.

PMID- 1376452
TI  - Identification of spinal electromotoneurons in the ray Raja clavata (Rajidae).
AB  - Retrograde transport of horseradish peroxidase injected ipsilaterally in several
      parts of the electric organ and light microscopy were employed to study
      motoneurons and electromotoneurons of the spinal cord in the weakly electric ray
      Raja clavata (Rajidae). The horseradish peroxidase-labelled electromotoneurons
      form a chain of cells located ventrolaterally in the gray matter of the spinal
      cord segments adjacent to the electric organ. The diameters of cells in the
      electromotor nucleus vary from 70 to 110 microns. When comparing other
      motoneurons of the spinal cord with electromotoneurons, the latter reveal no
      segmentation, whereas motoneurons yield accumulations which are close to
      metametric ones and are essentially smaller in size (averaging 33 microns in
      diameter).

PMID- 1376453
TI  - Serotonin-, substance P- and glutamate/aspartate-like immunoreactivities in
      medullo-spinal pathways of rat and primate.
AB  - Serotonergic neurons of the medulla oblongata have been proposed to play a role
      in the control of sensory, motor and autonomic cells in the spinal cord. Many of
      these raphe neurons have been shown to contain the undecapeptide substance P as
      well as the tripeptide thyrotropin-releasing hormone, but evidence for the
      presence of an excitatory amino acid in these pathways has not yet been
      documented. In colchicine-treated rats, we have used a combination of retrograde
      tracing and tri-color immunohistofluorescence techniques to study co-localization
      of serotonin- and substance P- with glutamate- or aspartate-like
      immunoreactivities in medullary neurons and the possible spinal projections of
      these cells. In addition, the distributions of serotonin-, substance P- and
      glutamate-immunoreactive terminal fields in the dorsal, ventral and lateral horns
      of the spinal cord were examined with tri-color immunofluorescence in the rat and
      the primate Macaca fasciculata. In colchicine-treated rats, glutamate- and
      aspartate-like immunoreactivity was found in practically all serotonin- and
      substance P-immunoreactive neurons of the B1, B2 and B3 cell groups. Some of
      these neurons also contained wheat-germ agglutinin conjugated to inactivated
      horseradish peroxidase and colloidal gold particles retrogradely transported from
      the spinal cord. In the spinal cords of non-colchicine-treated monkeys and rats,
      striking co-localization of serotonin, substance P- and glutamate-like
      immunoreactivities was seen in large boutons, surrounding the dendrites and cell
      bodies of large alpha motor neurons in the ventral horn. These observations
      suggest the existence of spinally projecting serotonin/substance P neurons
      containing excitatory amino acids such as glutamate or aspartate.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1376454
TI  - Recovery from unilateral 6-hydroxydopamine lesion of substantia nigra promoted by
      the neurotachykinin substance P 1-11.
AB  - Previous work has indicated that the neurotachykinin substance P may have
      nootropic and neurotrophic effects in vivo and in vitro raising the possibility
      that this neuropeptide may promote functional recovery from brain damage. This
      hypothesis was tested using the unilateral 6-hydroxydopamine lesion of the
      nigrostriatal dopamine system, as there is close anatomical and functional
      interaction between dopamine and substance P in this system. Rats were
      unilaterally injected with 6-hydroxydopamine into the substantia nigra, and,
      starting with the day after the lesion, were treated daily with peripheral
      injections of substance P (50 micrograms/kg, i.p.). The analysis of open-field
      behavior showed that, compared with vehicle-treated control lesions, substance P
      prevented the lesion-induced ipsiversive asymmetry in turning behavior and
      accelerated recovery from the ipsilateral asymmetry in thigmotactic scanning. The
      facilitatory effects of substance P were dependent on the degree of the lesion,
      as they were observed in animals with subtotal neostriatal dopamine depletions
      but not in those with near-total depletions. These results are discussed,
      firstly, with regard to the possible mechanisms of substance P on dopaminergic
      and non-dopaminergic systems, and secondly, with respect to their possible
      relevance in the study of neurodegenerative diseases.

PMID- 1376456
TI  - In situ hybridization: mRNA levels of secretogranin II, neuropeptides and
      carboxypeptidase H in brains of salt-loaded and Brattleboro rats.
AB  - In situ hybridization was used to study the mRNA levels for vasopressin, galanin,
      secretogranin II and carboxypeptidase H in salt-loaded and Brattleboro rats.
      These animals represent an in vivo model for the chronic stimulation of the
      hypothalamo-neurohypophyseal neurons. As shown by immunelectron microscopy
      secretogranin II is co-stored with vasopressin in these neurons. In salt-loaded
      rats the levels of mRNA for vasopressin, galanin and secretogranin II are
      increased in the paraventricular and supraoptic nuclei. Analogous changes were
      observed for Brattleboro rats with the exception of the vasopressin message which
      was decreased in these animals. The secretogranin II message was also increased
      in neurons which do not contain the vasopressin mRNA, i.e. in magnocellular
      neurons of the lateral hypothalamus and in the subfornical organ.
      Carboxypeptidase H message was also found in the paraventricular and supraoptic
      nuclei and in the subfornical organ; however, in both models the changes in mRNA
      in these nuclei were much lower than those observed for the secretory peptides or
      non-existent. We conclude that chronic stimulation of vasopressin neurons leads
      to a concomitant up-regulation of the biosynthesis of neuropeptides and
      secretogranin II. We suggest that the secretogranin II message might be a useful
      general marker for identifying chronically stimulated neurons.

PMID- 1376455
TI  - Distribution of neuronal cannabinoid receptor in the adult rat brain: a
      comparative receptor binding radioautography and in situ hybridization
      histochemistry.
AB  - The neuronal distribution of cannabinoid receptor in the adult rat brain is
      reported, combining receptor binding radioautography using the synthetic
      psychoactive cannabinoid ligand CP55,940 with in situ hybridization
      histochemistry using oligonucleotide probes complementary to rat cannabinoid
      receptor cDNA. In the cerebral cortex, especially in the frontal and cingulate
      cortex, dense binding was found in layers I and VI together with slight mRNA
      levels in a majority of both pyramidal and non-pyramidal-shaped neurons and of
      high mRNA levels in a moderate number of non-pyramidal-shaped neurons especially
      in layers II-III and V-VI. In the hippocampal dentate gyrus, very dense staining
      was found in the molecular layer together with high mRNA levels in a moderate
      number of hilar neurons close to the granular layer. In Ammon's horn, especially
      in the CA3 sector, very dense binding was found in the dendritic layers together
      with slight mRNA levels in the majority of the pyramidal cells and high mRNA
      levels in a moderate number of interneurons. In the basal ganglia, binding was
      very dense in the lateral putamen, substantia nigra pars reticulata, globus
      pallidus and entopeduncular nucleus, moderate in the medial putamen and caudate;
      and slight in the accumbens, together with slight to moderate mRNA levels in the
      striatal medium-sized neurons. Together with slight binding, slight to moderate
      mRNA levels were found in the majority of the neurons in the subthalamic nucleus.
      No binding and mRNA were found in the substantia nigra pars compacta and ventral
      tegmental area. Slight to moderate binding was found together with slight to
      moderate mRNA levels in the majority of neurons in the anterior olfactory
      nucleus; septum, especially medial septum and diagonal band of Broca; amygdala,
      especially basolateral amygdala; lateral habenula; ventromedial hypothalamic
      nucleus; lateral interpeduncular nucleus; central gray, dorsal cochlear nucleus;
      parabrachial nucleus; dorsal pontine tegmentum; pontine nuclei; commissural part
      of the nucleus tractus solitarius; inferior olive and dorsal horn of the spinal
      cord. In the cerebellum, very dense binding was found in the molecular layer
      together with slight mRNA levels in the majority of the granule cells and
      moderate mRNA levels in the basket and stellate cells. In conclusion, this study
      provides, for the first time, indirect assessment of the neurons containing
      cannabinoid receptor in the entire adult rat brain and will serve as a basis for
      future direct morphological confirmation using receptor immunohistochemistry and
      for functional studies.

PMID- 1376457
TI  - Corticotropin-releasing factor innervation of the locus coeruleus region:
      distribution of fibers and sources of input.
AB  - Electrophysiologic studies support the hypothesis that corticotropin-releasing
      factor, the neurohormone that initiates adrenocorticotropin release during
      stress, also serves as a neurotransmitter in the pontine noradrenergic nucleus,
      the locus coeruleus. To elucidate the circuitry underlying proposed corticotropin
      releasing factor neurotransmission in the locus coeruleus, the present study
      utilized immunohistochemical techniques to characterize corticotropin-releasing
      factor innervation of rat locus coeruleus and pericoerulear regions.
      Corticotropin-releasing factor-like immunoreactive fibers were identified in the
      locus coeruleus of colchicine- and non-colchicine-treated rats. However,
      corticotropin-releasing factor innervation of pericoerulear regions rostral and
      lateral to the locus coeruleus was more dense than that of the locus coeruleus
      proper. Double-labeling studies utilizing antisera directed against corticotropin
      releasing factor and tyrosine hydroxylase indicated that corticotropin-releasing
      factor-like immunoreactive fibers overlap with tyrosine hydroxylase-like
      immunoreactive processes of locus coeruleus neurons, particularly in rostral
      medial and lateral regions. A group of corticotropin-releasing factor-like
      immunoreactive neurons was localized just lateral to the locus coeruleus and
      numerous corticotropin-releasing factor-like immunoreactive neurons were
      visualized just ventral to the rostral pole of the locus coeruleus in a region
      corresponding to Barrington's nucleus. None of these corticotropin-releasing
      factor-like immunoreactive neurons were tyrosine hydroxylase-positive. To
      determine the source of corticotropin-releasing factor-like immunoreactive fibers
      in the locus coeruleus, injections of the retrograde tracer [wheat germ
      agglutinin conjugated to inactivated (apo) horseradish peroxidase coupled to gold
      particles] were made into the locus coeruleus and sections were processed for
      corticotropin-releasing factor-like immunoreactivity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1376458
TI  - Ultrastructural localization of hyaluronan in myelin sheaths of the rat central
      and rat and human peripheral nervous systems using hyaluronan-binding protein
      gold and link protein-gold.
AB  - Neural tissue of central (rat spinal cord) and peripheral origin (rat sciatic
      nerve, nerve fascicles of rat skin and iris and of human conjunctiva) was
      processed by osmium tetroxide/microwave fixation and embedded in epoxy resin.
      Hyaluronan-binding proteins and link proteins coupled to 15-20-nm gold particles
      were used as markers in a one-step post-embedding procedure for identifying
      hyaluronan (hyaluronic acid) at the ultrastructural level. All myelin sheaths in
      both rat and human material were found to be intensely labelled. The specificity
      of the hyaluronan-binding probes was demonstrated by the total loss of labelling
      following treatment of sections with hyaluronidase or by preincubating either the
      probes with hyaluronan oligosaccharides or the sections with unlabelled
      hyaluronan-binding protein. The identified hyaluronan appears to be located
      extracellularly, but is precise role here remains to be elucidated.

PMID- 1376459
TI  - Effect of vitamin E on acetylcholine-induced current in molluscan neurons: role
      of cytoplasmic free calcium and arachidonic acid.
AB  - Role of cytoplasmic concentration of free Ca2+ ([Ca]in) and arachidonic acid in
      potentiating the effect of vitamin E (DL-alpha-tocopherol) on acetylcholine
      receptor activity in Helix pomatia neurons was studied using a two-microelectrode
      intracellular recording, voltage clamp and fluorescent calcium probe fura-2
      technique. Elevation of [Ca]in by intracellular injection from a microelectrode
      or by depolarizing pulses and application of 0.1 microM-0.1 mM vitamin E enhanced
      the acetylcholine-induced chloride current both in LP11 and RBc4 neurons.
      Application of 10 microM arachidonic acid to the same neurons decreased this
      current. The use of fluorescent probe showed that vitamin E did not essentially
      change [Ca]in, but an increase of [Ca]in intensified both the enhancing effect of
      vitamin E and the depressing effect of arachidonic acid. The enhancing effect of
      calcium influx was considerably decreased after vitamin E application. The
      antioxidant action of vitamin E was probably not involved in the mechanism of its
      enhancing effect on acetylcholine-induced current, since synthetic antioxidant,
      ionol, depressed acetylcholine responses. A spectrum analysis has shown the
      interaction between vitamin E and arachidonic acid in solution. This interaction
      may be considered as the molecular mechanism responsible for the prevention by
      vitamin E of steady arachidonic acid production from membrane phospholipids and
      its down-regulatory effect on acetylcholine receptor activity. Our results
      support this suggestion, since an inhibitor of phospholipase A2, 4-bromophenacyl
      bromide, mimicked the enhancing effect of vitamin E.

PMID- 1376460
TI  - Health problems among Army children.
AB  - Of 782 Army families with children that were surveyed, over 10% reported one or
      more member with health problems or handicapping conditions requiring special
      ongoing treatment. However, less than half of these were enrolled in the
      Exceptional Family Member Program. Families with illnesses/handicaps that were
      enrolled in the program reported on the average more health problems than
      families with illnesses that were not enrolled.

PMID- 1376461
TI  - [Surgical treatment of gallbladder cancer].

PMID- 1376462
TI  - [Surgical technique and tactics and in the treatment of Crohn disease].

PMID- 1376464
TI  - A think-tank on nutrition in the primary prevention of low birthweight, cerebral
      palsy and related handicaps.

PMID- 1376465
TI  - A Golgi study on the olfactory bulb in the red stingray, Dasyatis akajei.
AB  - The intrinsic organization of the olfactory bulb (OB) was studied in the red
      stingray using the rapid Golgi method. The OB is horse shoe-shaped, surrounding
      the equator region of the nasal capsule. As seen in the sagittal sections, the OB
      is round with the long olfactory peduncle extending from the dorsocaudal region
      and the olfactory fibers in a thick bundle entering from the rostroventral
      aspect. Although not so distinct, the following areas are distinguished. A
      rostroventral ovoid area adjacent to the entrance of the olfactory fibers
      consists exclusively of the olfactory fibers running in various directions.
      Dorsocaudal to the olfactory fiber area is a wide crescent region containing thin
      bundles of olfactory fibers, olfactory glomeruli, mitral cells and a few
      disseminated granule cells. A narrow crescent area made up of scattered granule
      cells is located dorsocaudally to the above wide crescent area. The outermost
      region consists of a fiber layer encapsulating the dorsal to caudal aspect of the
      OB. Thus, while the major constituents of the vertebrate OB are recognized, the
      lamination is very obscure.

PMID- 1376463
TI  - [The neuroendocrine system of the liver].

PMID- 1376466
TI  - Dendritic arbolization of large pyramidal neurons in the motor cortex of normal
      and reeler mutant mouse.
AB  - Reeler, an autosomal recessive mutation in mice, is characterized by abnormal
      positioning of the neurons in the cerebral cortex. We performed a descriptive
      analysis on the arborization of dendritic processes of large pyramidal neurons in
      the motor cortex (hindlimb area) of normal and reeler mice, as seen in the Golgi
      preparations. In the normal mouse, somata of large pyramidal neurons were located
      in the layer V, and their apical dendrites ascend vertically to the pial
      surfaces. Their basal dendrites proceed horizontally or inferiorly. In the reeler
      mouse, typical large pyramidal neurons with a normal (upright) apical dendrite
      and a variety of atypical large pyramidal neurons with a disoriented apical
      dendrite were radially scattered within the motor cortex. Typical large pyramidal
      neurons occupied the lower half of the motor cortex, whereas atypical large
      pyramidal neurons were predominantly observed in the upper half of the motor
      cortex. Atypical large pyramidal neurons were further divided into inverted,
      tumbled, V-shaped, bipolar and superficial polymorphic cells, as previously
      reported (Terashima et al., J. Comp. Neurol. 218:314-326, 1983). Superficial
      polymorphic cells localized in the layer of polymorphic cells and the layer of
      the large pyramidal cells were characterized by the extremely poor dendritic
      arborizations and the smooth surface of the dendrites, which suggests development
      of dendrites of these neurons was deranged by the reeler genetic locus.

PMID- 1376468
TI  - Effect of hypoxemia on fetal hemoglobin synthesis during late gestation.
AB  - This study was carried out to investigate the effect of fetal hypoxemia, as a
      result of acute intermittent maternal hypoxia, on the switchover from fetal to
      adult type Hb as well as Hb oxygen affinity and 2,3-diphosphoglycerate levels in
      the near-term fetus. These experiments were carried out using 10 fetal lambs with
      gestational ages ranging from 132 to 140 d. After the installation of appropriate
      fetal catheters, five of the ewes were exposed to an air mixture containing 10%
      O2 for 90 min/d for 4 consecutive d. Blood samples were withdrawn before the
      beginning of the hypoxic experiments and between the 5th and 6th d after the
      first episode of hypoxia. These samples were for the determination of 2,3
      diphosphoglycerate concentration, arterial O2 pressure at which Hb is 50%
      saturated, and Hb type synthesis. Blood gases were monitored during each hypoxic
      episode. During the hypoxia, fetal arterial O2 pressure decreased from 2.43 +/-
      0.36 kPa (18.2 +/- 2.7 mm Hg) to 1.57 +/- 0.17 kPa (11.8 +/- 1.3 mm Hg). These
      values returned to their initial levels after cessation of the maternal hypoxia.
      Five control animals of the same gestational age were also followed. During the
      interval of the study, a decrease of fetal Hb synthesis was noted (71.7 +/- 12.1
      to 57.4 +/- 10.2%, p less than 0.001) in the control group. However, the level of
      fetal Hb synthesis did not significantly change in the hypoxic group (85.1 +/-
      11.1 versus 80.6 +/- 18.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376467
TI  - Analyses of salivary components in leukemia patients receiving chemotherapy.
AB  - We analyzed several salivary components in stimulated whole saliva from patients
      with acute leukemia who were undergoing chemotherapy. Saliva samples were
      collected at the time of diagnosis and longitudinally during the treatment
      period. Data analyses showed that patients with leukemia had significantly higher
      peroxidase and amylase activity and elevated concentrations of total protein at
      the time of diagnosis. After induction chemotherapy these parameters returned to
      normal values and remained constant during the observation period. At the time of
      diagnosis no significant differences in thiocyanate (SCN-) concentrations were
      found in saliva samples from control subjects and patients with leukemia.
      Treatment with cytotoxic agents resulted in granulocytopenia and a concomitant
      decrease in the SCN- concentration in saliva. The function of the salivary
      peroxidase system is impaired by the decrease in SCN- concentration, which may be
      a contributing factor to some of the oral complications that occur in patients
      undergoing chemotherapy.

PMID- 1376469
TI  - Nursing care of patients with esophageal cancer.
AB  - Esophageal cancer is an uncommon but aggressive disease with the potential for
      early metastasis. The majority of patients will present with metastatic disease,
      and treatment is usually palliative. This affects the physical and psychosocial
      needs of the patient and family. The nurse plays a crucial role in the care of
      these individuals and, therefore, needs a current and in-depth understanding of
      the disease, its treatment, and its nursing management.

PMID- 1376470
TI  - Using humorous signs for bleeding precautions.

PMID- 1376471
TI  - Relative incidence and mortality of congenital heart defects diagnosed by
      angiohemodynamic methods: a 17-year study.
AB  - Over a 17-year period (January 1971 to January 1988), 2322 children, aged 0-14
      years, were diagnosed as having congenital heart disease (CHD) by cardiac
      catheterization and angiography. Excluding those with highly complex or
      undiagnosed defects, there were 2156 children with CHD, 72.4% of whom were
      treated surgically, with a total surgical mortality rate of 24.1%. After a mean
      follow-up of 9 years the overall mortality of the cohort was 29.9%, 29.1%
      occurring in the first month of life, 39.6% between 1 month and 1 year, and 31.2%
      between 1 and 14 years. The incidence, mortality, and age at death of each
      cardiac defect are presented and compared with the results of other studies. The
      overall mortality for congenital heart defects in eastern Spain remains elevated,
      whereas there has been a significant decrease in neonatal mortality and a trend
      towards a lower mortality in the last years of the study.

PMID- 1376472
TI  - Balloon atrial septostomy under transesophageal echocardiographic guidance.
AB  - Balloon atrial septostomy is an established method of palliation for several
      forms of congenital heart disease. Previously performed under fluoroscopic x-ray
      control, recent reports have demonstrated the utility of transthoracic
      echocardiographic monitoring. We report the first application of uniplane
      transesophageal echocardiography (TEE) (6.7-mm probe) as an alternative imaging
      modality for control of balloon atrial septostomy on neonates in the intensive
      care unit.

PMID- 1376473
TI  - Dyskeratosis congenita associated with elevated fetal hemoglobin, X-linked ocular
      albinism, and juvenile-onset diabetes mellitus.
AB  - An 11-year-old boy had dyskeratosis congenita, elevated fetal hemoglobin level, X
      linked ocular albinism, and juvenile-onset diabetes mellitus. A review of the
      international literature revealed that elevated fetal hemoglobin has been noted
      in 15 reported cases of dyskeratosis congenita. It is a previously unrecognized,
      commonly associated finding in dyskeratosis congenita that may provide insight
      into the location and function of the gene for dyskeratosis congenita.

PMID- 1376474
TI  - Eruptive vellus hair cysts: case report and review of the literature.
AB  - A 6-year-old Caucasian girl had dozens of asymptomatic, flesh-colored, 2- to 5-mm
      eruptive vellus hair cysts. These papules on the buttocks, thighs, and groin
      increased in number for three months. Histologic examination revealed poorly
      defined, keratin-filled cysts in the upper middermis, containing numerous
      transversely or obliquely cut portions of vellus hair. The histopathologic
      differential diagnosis with other epithelial cysts containing hair shafts is
      debated, and new clinical differential diagnoses are proposed. Review of the
      literature suggests that eruptive vellus hair cyst is not a rare disorder, but
      its frequency is probably underestimated due to paucity of symptoms.
      Nevertheless, the clinical relevance of some of the differential diagnoses should
      convince clinicians to obtain histologic confirmation.

PMID- 1376475
TI  - [Perivascular hyalin substance and calcinosis of the gingiva after cyclosporin A
      therapy--a new finding].

PMID- 1376476
TI  - [Use of octreotide in the treatment of digestive endocrine tumors. A French
      multicenter study].
AB  - Morbidity and mortality in endocrine gastro-enteropancreatic (GEP) tumours are
      mainly related to the clinical consequences of tumoral peptide hypersecretion.
      Surgical resection at an early stage is the only curative treatment. However,
      most tumours are detected only when the hypersecretory state reflects the
      presence of metastases; surgery and chemotherapy then give only palliative
      results counterbalanced by serious side-effects. Somatostatin inhibits most
      endocrine secretions of the GEP tract and thus can alleviate invalidating
      symptoms. Its use is limited by its short half-life (2 min), the necessity of
      i.v. infusion and the possibility of a rebound phenomenon. Octreotide, a
      synthetic somatostatin analogue with a long duration of action, is administered
      subcutaneously and allows ambulatory treatment. In our series of 78 patients we
      observed about 80 percent of excellent or good clinical results, enabling the
      patients to resume normal life. Only minor and transient side-effects were noted.
      The overall tolerance of the drug was considered excellent or good. Prolonged
      administration of octreotide is a safe and effective symptomatic treatment in
      patients without any restriction of anti-tumoral procedures. Furthermore, it
      prevents the severe carcinoid crises that occur during surgery or embolization in
      patients with carcinoid syndromes.

PMID- 1376477
TI  - Kinetic study of the helix to coil dark reaction of poly(spiropyran-L-glutamate).
AB  - An investigation of kinetics of the helix to coil dark reaction of light adapted
      poly(spiropyran-L-glutamic acid) (PSLG) dissolved in hexafluoroisopropanol was
      performed. The reaction was associated with the spiropyran (SP) to merocyanine
      (MC) ring opening. The ring opening reaction monitored with UV/VIS spectroscopy
      showed first order kinetics. Chromophore and polypeptide backbone circular
      dichroism data fit to an expression consistent with a single intermediate series
      mechanism. By FTIR, we monitored the polypeptide alpha-helix amide I, the MC
      chromophore--C = C--stretch and the protonated unmodified carboxylate C = O
      stretch bands. During the first step of the series mechanism, changes in the
      hydrogen bonding of the unmodified carboxylate groups occurred, suggesting
      breakup of polypeptide aggregates. The second step of the proposed series
      mechanism was dominated by the helix to coil transition and the ring opening of
      SP to MC. The CD spectrum of MC in the dark adapted PSLG was red shifted and had
      a narrower bandwidth than the UV/VIS spectrum. The kinetic and spectroscopic data
      suggested that a fraction (population I) of the MC chromophores experienced
      optical activity induced by the chiral polypeptide environment, while the
      remainder of the MC chromophores (population II) were solvated and enantiomeric.

PMID- 1376479
TI  - [RNA editing in higher plants].

PMID- 1376478
TI  - Role of sodium cromoglycate on analgesia, locomotor activity and opiate
      withdrawal in mice.
AB  - The role of sodium cromoglycate (CRO) on analgesia, locomotor activity and
      morphine withdrawal in mice was studied in morphine-dependent and drug-naive
      mice. CRO (0.5, 1, 5, 10, 30, 50 and 100 mg/kg, SC) induces analgesia (hot
      plate), an effect blocked by previous administration of the opiate antagonist
      naloxone (1 mg/kg). Furthermore, CRO (30 mg/kg) potentiates morphine analgesia.
      In morphine-tolerant mice, moderate doses of CRO (0.5, 1, 5, 10 and 30 mg/kg) do
      not induce analgesia, which suggested the development of cross tolerance between
      CRO and morphine, whereas coadministration of CRO and morphine in morphine
      tolerant animals restored the sensitivity to morphine. Administration of CRO (10
      and 30 mg/kg) induces an increase in spontaneous locomotor activity, and previous
      administration of naloxone (1 mg/kg) blocks this effect, whereas CRO (10 mg/kg)
      blocks morphine (10 mg/kg) and amphetamine (3 mg/kg)-induced hyperactivity. CRO
      (10, 50 and 100 mg/kg) induces a significant and dose-dependent reduction in the
      number of jumps ("jumping up") during naloxone (1 mg/kg)-induced withdrawal in
      morphine-dependent mice. Finally, CRO (100 mg/kg) reduces the "wet dog shake"
      phenomenom during naloxone-induced withdrawal in morphine-dependent mice. These
      results suggest a possible stabilizing effect of CRO on the membranes of neurones
      that mediate analgesia, locomotor activity and opiate abstinence. Changes and
      inhibition of DA, NA and 5-HT release may also explain these effects.

PMID- 1376480
TI  - [The US-guided positioning of intraprostatic metal spirals. Preliminary
      experience].
AB  - The authors report their preliminary experience with the insertion of
      intraprostatic spirals in the treatment of chronic urinary retention due to
      prostatic hypertrophy in 8 inoperable patients. The value is stressed of
      transrectal US guidance during spiral insertion together with the advantages of
      US over other positioning techniques (i.e., better visualization of prostatic
      urethra and urethral sphincter, real time visualization of spiral progression and
      correct positioning). All patients were successfully treated without
      complications; spiral positioning was easier in the patients with a Foley's
      catheter (22 CH). US-guided positioning of intraprostatic spirals appears an easy
      and safe treatment of chronic urinary retention in inoperable patients.

PMID- 1376481
TI  - In vivo and in vitro interaction of trichloroethylene with macromolecules from
      various organs of rat and mouse.
AB  - Trichloroethylene was covalently bound in vivo to DNA, RNA and proteins of rat
      and mouse organs 22 hr after ip injection. The covalent binding index values of
      rat and mouse liver DNA classify trichloroethylene as a weak initiator. Labeling
      of RNA and proteins from various organs of both species was higher than that of
      DNA. In vitro, trichloroethylene was bioactivated by microsomal fractions
      dependent on cytochrome P450, mainly from liver of both species, to
      intermediate(s) capable of binding to exogenous DNA. No particular species
      specific difference was evident except for mouse lung microsomes which were more
      efficient than rat lung microsomes. GSH-transferases capable of bioactivating
      P450-dependent were present in mouse lung microsomes and in liver microsomes of
      both species. These data, along those previously reported, provide sufficient
      evidence for a weak ability of TCY to interact covalently with DNA.

PMID- 1376482
TI  - Analysis of premature ventricular counts in long term ECG following myocardial
      infarction.
AB  - Frequent and recurrent ventricular premature beats (VPB's) are considered to be
      associated with a higher risk of sudden cardiac death, particularly for survivors
      of myocardial infarction (MI). The distribution of VPB's has a large probability
      mass at zero, and a very heavy right hand tail. In this research, we fitted a
      model to VPB for patients for which VPB was present. The model was fitted on the
      basis of a relatively large data set on MI survivors in Israel. The model was
      fitted by a method which is based on the generalized linear model. This method,
      which was introduced by Zeger and Liang, is designed for longitudinal data and
      uses the quasi-likelihood concept. No specific assumptions are required on the
      shape of the distribution of the dependent variable. The results indicate that
      the model fits the data quite well but underestimates the very extreme high
      values. This research demonstrates the applicability of generalized linear models
      for longitudinal non-Gaussian data. Such data often arise in medical studies. The
      study also points out the distributional properties of VPB counts. In particular,
      it shows their associations with simple clinical and epidemiological variables,
      and with certain time periods during the day.

PMID- 1376483
TI  - [Acute liver failure: current hepatological-surgical therapy strategies].
AB  - Patients with acute liver failure, characterized by deep jaundice, hepatic
      encephalopathy within eight weeks from the start of symptoms, are subjected to
      intensive care treatment. New drugs (Interferons, Prostaglandins) have been
      applied to these patients, with variable results. Mortality of fulminant hepatic
      failure is high in patients who don't respond to intensive therapy. These
      patients are characterized by progressive hepatic encephalopathy, decrease of
      clotting factors, especially of factor 5 and constantly increased serum
      bilirubin. Results of a multivariate analysis disclosed a poor prognosis in the
      individual patient more then 40 years old or under 11 years, with a prothrombin
      time below 10% of control, serum bilirubin over 300 mmol/l and with a late onset
      of hepatic encephalopathy after long standing jaundice.

PMID- 1376484
TI  - [Diagnosis and therapy of hepatorenal syndrome].
AB  - Hepatorenal syndrome (HRS) is defined as severe vasoconstriction of renal
      cortical vessels with critical impairment of glomerular filtration rate,
      initiated by deteriorating liver function. In addition, systemic vasodilation,
      predominantly of splanchnic vessels is present. Although the urinary status is
      basically normal, during the course of HRS kidneys are loosing their ability to
      concentrate and at an urinary production rate of less than 100 ml/day the urinary
      osmolarity and Na(+)-concentration drops significantly. Because HRS can not be
      improved by conventional medical treatment regimens, its prophylaxis is of major
      importance. Besides improvement of liver function and avoidance of drastic volume
      depletion (bleeding, paracentesis, high dose diuretic therapy) and sepsis, the
      therapeutic goal is to reverse systemic vasodilation and to achieve a concomitant
      relaxation of renal arteries. Expansion of plasma volume and application of renal
      vessel dilating prostaglandins is one strategy. Alternatively, therapy with
      ornipressin was shown to be successful, which improves renal perfusion and
      normalizes the hyperdynamic state of systemic circulation.

PMID- 1376485
TI  - [Early diagnosis of hepatocellular carcinoma].
AB  - In every patient, in particular males of all ages presenting with chronically
      progressive diseases or cirrhosis of the liver, ultrasonography and an AFP test
      should be performed at intervals of six months. If hepatocellular carcinoma of
      the liver (HCC) is suspected (i.e. by increase of AFP or a positive result in
      ultrasonography), diagnosis should be confirmed by further investigations such as
      fine-needle biopsy guided by sonography, angiography and CT-scan. Adequate
      therapeutical measures such as resection of the tumor, chemotherapy, injection of
      alcohol or liver transplantation can thus be initiated in time. Besides efforts
      for early diagnosis of carcinoma of the liver, preventive measures (vaccination
      for hepatitis B, restrictive use of blood transfusion, reduction of alcoholism,
      thorough therapy of hemochromatosis, etc.) may contribute to the reduction of
      chronic diseases of the liver and of associated HCC.

PMID- 1376486
TI  - [Degenerative aphasia or progressive primary aphasia and related syndromes].

PMID- 1376487
TI  - Real time analysis of antibody-antigen reaction kinetics.
AB  - Surface plasmon resonance, i.e. detection of changes in refractive index on a
      surface, was used in a biosensor to evaluate the dissociation/association rate
      and affinity constants of human monoclonal IgG and IgM antibodies and Fab
      fragments. The results showed that an observed difference in affinity constants
      between intact and fragmented IgG anti-tetanus antibody was related to
      approximately 10-fold differences in dissociation rate constants, since the
      association rate constants were in the same range, i.e. 2-3 x 10(5) (M-1 s-1).
      Affinity constants, as determined by conventional solid phase enzyme immunoassay,
      were substantially higher than the constants produced by the biosensor. Human
      monoclonal IgM anti-Tn alpha antibodies showed, furthermore, one order of
      magnitude higher association rate constants, as compared with the IgG antibodies,
      but since the dissociation rate constants were more than ten times higher, the
      resulting affinity constants of the anti-carbohydrate IgM antibodies were still
      somewhat lower than those of the IgG antibodies.

PMID- 1376488
TI  - Spontaneous IgM autoantibody production in vitro by B lymphocytes of normal human
      neonates.
AB  - Human neonate B lymphocytes display unique phenotypic and functional
      characteristics: in addition to CD1c antigens, CD5+ and CD5- subsets both express
      activation markers such as CD23 and Bac-1. They proliferate strongly in the
      presence of various lymphokines (rIL-2, rIL-4, low molecular weight BCGF), but
      differentiate poorly in the presence of the same lymphokines, pokeweed mitogen
      and Epstein-Barr virus. It has also been reported that human neonate B
      lymphocytes produce polyreactive autoantibodies after in vitro activation by
      Staphylococcus aureus Cowan I and transformation by Epstein-Barr virus. We now
      show that, in the absence of in vitro stimulation, human neonate B lymphocytes
      produce polyreactive antibodies of the IgM isotype against several autoantigens.
      The B lymphocytes involved expressed membrane IgD, IgM, CD23 and CD11b molecules;
      CD5 expression was variable. This phenotype was consistently found on a minority
      of B lymphocytes and is similar to that of polyreactive autoantibody-producing B
      cells in mice. We also found that autoantibody production in vitro could occur in
      the absence of any T helper effect. The function of these autoantibodies is not
      clearly established, but their occurrence in a large proportion of human neonates
      strongly suggests that they play an important role in the development of the
      immune system.

PMID- 1376490
TI  - Resistance to collagen-induced arthritis in Biozzi mice is not associated with a
      defect in autoantibodies to accessible epitopes on cartilage collagen.
AB  - In order to understand why most strains of Biozzi mice are unexpectedly either
      arthritis-resistant, or susceptible, we investigate the autoantibody reactivity
      against matrix-embedded collagen molecules. We show a close correlation between
      these tissular and the free collagen antibodies, irrespective of arthritis
      susceptibility. These results are against an antibody response restricted to
      hidden non-pathogenic epitopes in the resistant mice.

PMID- 1376489
TI  - Expression and regulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in
      human intestinal epithelial cell lines.
AB  - T cells and other leucocytes regularly occur within and subjacent to the gut
      epithelium. Recent data suggest that intestinal epithelial cells may exert
      accessory immunological functions. Although interactions between leucocytes and
      accessory cells usually require expression of adhesion molecules, intestinal
      epithelium has generally been considered negative for intercellular adhesion
      molecule-1 (ICAM-1) by immunohistochemical techniques. We therefore studied the
      expression of ICAM-1 and lymphocyte function-associated antigen-3 (LFA-3) by two
      colonic epithelial cell lines and found that both adhesion molecules were
      constitutively present at low levels. ICAM-1 protein expression could be enhanced
      within 4 h by cytokines, particularly after co-incubation with interferon-gamma
      (IFN) and tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), or IL-6.
      IFN also resulted in accumulation of ICAM-1 mRNA. Conversely, the LFA-3
      expression was virtually unaffected by cytokine stimulation. These data imply
      that intestinal epithelial cells under certain conditions may bear adhesion
      molecules required for cooperation with juxtaposed leucocytes in situ, and that
      the expression of some of these molecules is modulated by cytokines from
      activated mucosal leucocytes.

PMID- 1376491
TI  - Cells of cerebrospinal fluid of multiple sclerosis patients secrete antibodies to
      myelin basic protein in vitro.
AB  - To characterize the role of B lymphocytes in the pathogenesis of Multiple
      Sclerosis (MS), we have isolated mononuclear cells from cerebrospinal fluid (CSF)
      and stimulated them with a polyclonal B-cell mitogen (pokeweed mitogen). This
      study has been done with MS patients selected for the occurrence of an acute
      attack in the course of the disease and with patients hospitalized for other
      neurological diseases. Five of the 11 MS patients had B lymphocytes producing in
      vitro antibodies (Abs) directed against purified human myelin basic protein
      (hMBP), as revealed by Western blot analysis. None of the 20 patients with other
      neurological diseases showed such a reactivity. The produced Abs recognized only
      1 or 2 hMBP peptides without dominance for a certain peptide. This result
      emphasizes the presence of B cells producing Abs against MBP in CSF of MS
      patients and shows the interest of studying mononuclear cells of CSF as a good
      marker of the pathogenesis.

PMID- 1376492
TI  - Dissimilar biosynthesis of interleukin-6 by different areas of synovial membrane
      of patients with rheumatoid arthritis and osteoarthritis.
AB  - In this study the IL-6 production was studied by synovial cells isolated from
      patients with either rheumatoid arthritis (RA) or osteoarthritis (OA). The
      kinetics of spontaneous IL-6 production differs in both groups. Furthermore, the
      induction of IL-6 by bacterial lipopolysaccharide (LPS) in synovial cell cultures
      of RA is much more rapid than in those of OA patients. On the other hand, more
      PGE2 was detected in culture supernatants from synovial adherent cells of OA than
      in those of RA patients. We also compared the IL-6 production and the amount of
      IL-6 mRNA in fragments derived from the areas of synovial tissue showing
      macroscopic signs of intensive inflammation (area A), with those from relatively
      intact (area B) synovial sites. In synovial fragments, but not in isolated
      adherent cells at area A the in vitro IL-6 production starts earlier in RA than
      in OA. In the area A, significantly more CD14+, CD43+ and HLA-DR+ cells were
      detected than in the other compartment less involved in local inflammatory
      events.

PMID- 1376493
TI  - Soluble interleukin-2 receptors in children with juvenile chronic arthritis.
AB  - Concentrations of interleukin-2 receptors were studied in sera of 81 patients
      with pauciarticular-, polyarticular-, and systemic-onset juvenile chronic
      arthritis using a double antibody "sandwich" enzyme-linked immunosorbent
      technique. Serum concentrations were significantly increased in all subgroups
      when compared with the healthy controls. Higher concentrations were found in
      systemic onset disease than in pauci- or polyarticular onset disease. Serum
      levels were found to be increased in both inactive and active disease, showing
      maximal values in patients with systemic features. A correlation to C-reactive
      protein, alpha 1-acid glycoprotein, and erythrocyte sedimentation was observed.
      Increased sIL-2R values suggest disease activity despite the absence of clinical
      symptoms.

PMID- 1376494
TI  - [Therapy of arrhythmias in clinical practice].
AB  - The primary care physician should be cautious and restrictive in the treatment of
      cardiac arrhythmias and adhere to the well established modalities only. For
      supraventricular arrhythmias digitalis, verapamil, quinidine and betablocking
      agents are the drugs of choice. In atrial fibrillation oral anticoagulants and in
      some cases aspirin seem to be beneficial for the prevention of stroke in selected
      subgroups of patients. Criteria for their use are outlined in Tables 1 and 2.
      Ventricular arrhythmias in healthy persons generally should not be treated. In
      patients with coronary artery disease and severely compromised left ventricular
      function amiodarone is very effective for the treatment of complex ventricular
      arrhythmias. If other antiarrhythmics are to be used, the advice of a
      cardiologist is strongly recommended, as proarrhythmic effects are particularly
      common in severe cardiac conditions. Severely symptomatic patients with recurrent
      ventricular tachycardia and syncope should be offered invasive evaluation in
      order to determine effective medical or surgical treatment.

PMID- 1376495
TI  - Finding RNA makes proteins gives 'RNA world' a big boost.

PMID- 1376496
TI  - New horizons for RNA catalysis.

PMID- 1376497
TI  - Therapeutic landscapes: medical issues in light of the new cultural geography.
AB  - Employing an expanded meaning of the concept of landscape taken from the 'new'
      cultural geography, this paper explores why certain places or situations are
      perceived to be therapeutic. Themes from both traditional and recent work in
      cultural geography are illustrated with examples from the literature of the
      social science of health care. The themes include man-environment relationships;
      humanist concepts such as sense of place and symbolic landscapes; structuralist
      concepts such as hegemony and territoriality; and blends of humanist concerns,
      structuralist concerns, and time geography. The intention of this broad overview
      is to bring some particularly useful concepts developed in cultural geography to
      the attention of social scientists interested in matters of health and to
      stimulate research along new lines.

PMID- 1376498
TI  - Child developmental delay and socio-economic disadvantage in Australia: a
      longitudinal study.
AB  - Socio-economic inequalities in adult and child health in Australia have been an
      issue of national concern. While a large body of data has discussed adult health,
      there have been relatively few Australian reports of socio-economic inequalities
      in child health. This occurs in a context where there have been increases in the
      proportion of Australian children living in poverty and where there has been an
      increased interest in child developmental delay as an indicator of child health
      status. This paper reports the result of a longitudinal study of pregnancy
      outcomes and one indicator of child health, namely child developmental delay.
      Three indicators of socio-economic status (chronic socio-economic disadvantage,
      mother's education, family income) were used to predict child developmental
      delays observed some 5 1/2 years after the study commenced. Mothers who had the
      lowest socio-economic status (using any of the indicators) had substantially
      higher rates of children manifesting developmental delays.

PMID- 1376499
TI  - 'Culture' in culture-bound syndromes: the case of anorexia nervosa.
AB  - Anorexia nervosa is presently considered a Western culture-bound syndrome. A
      cultural focus on dieting and ideals of thinness for women are assumed to be
      implicated in the disorder. While research indicates that the majority of non
      anorectic women in the United States are preoccupied with body weight and
      dieting, it is not clear what 'thinness' means to anorectics themselves or that
      norms about dieting are always involved in subjective experiences of anorexia.
      Meaning-centered studies of anorectics--especially those in non-clinical settings
      -are needed to clarify the cultural contexts of the disorder. Case studies of two
      anorectic women from Minneapolis-Saint Paul, Minnesota, show that for some
      anorectics self-starvation is encoded in religious idioms and symbols about the
      body, food, and self. A review of the literature illustrates a long-standing
      relation between self-starvation and religious ideals in Western culture and
      points to an association between contemporary anorexia nervosa and asceticism.
      The case studies presented here demonstrate that this asceticism may be
      subjectively expressed through religious concepts about the body and food and
      suggest that future research formally investigate the religious practices and
      beliefs of anorectics seen clinically. The author explores the implications of
      these findings for definitions of 'normality' and 'abnormality,' key issues in
      ethnopsychiatry. These findings also suggest that future cross-cultural research
      might examine asceticism about the body and food in religions other than Judeo
      Christian, cultural groups with rituals of fasting and vomiting, and the presence
      of fundamentalist churches and missionaries in those non-Western cultures for
      which there are recent reports of eating disorders. Anorexia nervosa's
      designation as a syndrome limited to Western cultures or to those cultures
      influenced by them may reflect unexamined assumptions on the part of researchers
      that dieting and secular ideals of slimness are primarily involved in the
      disorder.

PMID- 1376500
TI  - Human platelets deficient in dense granules contain normal amounts of pp60c-src.
AB  - We have determined that pp60c-src, a protein tyrosine kinase abundant in normal
      platelets, is present at comparable levels in platelets that are deficient in
      dense granules (Hermansky-Pudlak syndrome). Relative quantitation of pp60c-src
      was performed by immunoblot analysis after protein separation by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. Our data suggest that human platelet
      dense granules, unlike chromaffin cell secretory granules, are not the major
      intracellular site of localization of pp60c-src.

PMID- 1376501
TI  - The effect of FK506 treatment on pancreaticoduodenal allotransplantation in the
      primate.
AB  - The effect of FK506 monotherapy on pancreaticoduodenal allotransplantation was
      studied in a primate model. The recipients were made diabetic by total
      pancreatectomy, thus glycemic control depended on the graft. In control animals
      hyperglycemia occurred after 14 +/- 3 days and the animals died after 36 +/- 15
      days. For FK506-treated animals, the time until development of hyperglycemia was
      60 +/- 12 days (P less than 0.05). The animals were then sacrificed by day 90 (P
      less than 0.05). All three control animals lost their graft function because of
      severe rejection, as verified by postmortem examination. Only one of the five
      treated animals showed evidence of a moderate-to-severe rejection at 90 days, one
      animal having a mild rejection as judged by the histological findings. The drug
      was clinically well tolerated in all except one animal that became apathetic and
      refused to eat. Hyperglycemia and an elevated serum creatinine level, which were
      probably related to the FK506 treatment, occurred in one animal each. Both of
      these side-effects were reversed by reducing the dose. Thus the use of FK506
      permits successful single pancreatic transplantation in primates.

PMID- 1376502
TI  - Prediction by postrevascularization biopsies of cadaveric kidney allografts of
      rejection, graft loss, and preservation nephropathy.
AB  - This prospective study of postrevascularization biopsies was undertaken to
      determine if pathological changes might be correlated with subsequent allograft
      rejection and loss. Such a relationship, if identified, could be used to predict
      graft outcome, thus permitting earlier intervention for individuals at an
      increased risk for rejection or graft loss. Fifty-seven biopsies were obtained,
      and the number of polymorphonuclear leukocytes marginating in the glomerular
      loops and peritubular capillaries was documented along with risk factors
      associated with the recipients' immunological status and with risk factors
      associated with ischemic preservation injury. The presence of seven PMN
      leukocytes in the peritubular capillaries is related to the subsequent occurrence
      of cellular rejection and accurately predicted in 82% of the patients studied
      whether or not rejection would occur. Mean glomerular PMN leukocyte count was
      related to cold ischemia time and subsequent graft loss, while an elevated mean
      glomerular PMN leukocyte count in conjunction with an elevated peritubular PMN
      leukocyte count was always associated with hyperacute rejection. Focal glomerular
      thrombosis (less than 50%) and tubular cast formation are manifestations of
      preservation nephropathy and had no effect on graft outcome. These findings
      suggest that the peritubular capillaries are a more sensitive target for immune
      changes and that minor donor/recipient disparities can be detected in the
      peritubular capillaries while preexisting sensitization to the donor is reflected
      by concurrent changes in the glomerular and peritubular capillaries.

PMID- 1376506
TI  - The effect of osmolality and glucose concentration on the purity of human islet
      isolates.

PMID- 1376505
TI  - The splenic artery as the inflow in arterial revascularization of the liver graft
      in clinical liver transplantation.

PMID- 1376504
TI  - Evidence that changes in expression of major histocompatibility complex antigens
      may underlie the immunosuppressive effect of heat-treated cells in vivo and in
      vitro.
AB  - The prior transfusion of heat-treated (60 degrees C for 1 hr) allogeneic spleen
      cells is known to bring about specific prolongation of the survival of subsequent
      donor strain heart allografts. In this communication we show that some
      polymorphic and monomorphic class 1 determinants on spleen cells are heat
      denatured so that they no longer provoke antibody formation in naive allogeneic
      hosts. By contrast, the heated cells remain able to provoke the formation of anti
      class 2 antibodies. When measured in a binding assay, the levels of anti-class 2
      antibodies are similar irrespective of whether the immunizing inoculum consists
      of normal or heated cells. In a cytotoxic assay, the antibodies produced
      following exposure to normal cells are cytotoxic; this activity is substantially
      reduced when the cellular immunizing inoculum is heated. Cells heated to 60
      degrees C for 1 hr are unable to stimulate in a mixed lymphocyte reaction, but
      reactivity can be partially restored by the addition of exogenous IL-2 to the
      culture. From previous evidence it seems unlikely that suppressor cells play a
      major role in the immunosuppression effected by cells heated to 60 degrees C. The
      results presented in this communication suggest a possible role for anticlass 2
      antibodies and also imply the defective production of a costimulatory signal that
      normally follows the presentation of allogeneic MHC antigens.

PMID- 1376503
TI  - A prospective, randomized, blind comparison of three biopsy techniques in the
      management of patients after renal transplantation.
AB  - Although conventional histology (CH) of needle core biopsies has been accepted as
      the gold standard for diagnosis of renal allograft rejection, this assumption has
      never been tested. Fine-needle aspiration cytology (FNAC) and monoclonal antibody
      (panleukocyte) staining of needle core biopsies (MABS) have been suggested to be
      superior to CH. A total of 50 patients received a cadaveric renal transplant
      followed by immunosuppression with triple therapy. Biopsies were taken routinely
      at days 7,14,21,28, and 90, with additional biopsies taken between these times if
      rejection was suspected (total biopsy sessions = 219). Specimens were taken for
      CH, FNAC, and MABS at each biopsy session, but only the result of one technique
      (previously randomly allocated) was communicated back to the clinical team, using
      a standardized grading system. Subsequently the presence or absence of rejection
      was determined by retrospective analysis of the clinical and biochemical course
      by 4 clinicians, without reference to the biopsy result. Graft survival was not
      significantly different in the three groups. The sensitivities for CH, FNAC, and
      MABS were 75%, 59%, and 77%, respectively, while the specificities were 87%, 96%,
      and 80%, respectively. Inadequate samples for analysis occurred frequently with
      the MABS technique--and, to a lesser extent, with CH--and both techniques tended
      to overdiagnose rejection. FNAC most often gave an answer but did miss clinically
      important rejection episodes. Needle-core biopsy processed for CH remains the
      most reliable biopsy technique for the diagnosis of rejection of renal
      allografts. FNAC is a useful technique for monitoring grafts with stable function
      or nonfunction. MABS does provide information equivalent to CH, but, in this
      study, had a high incidence of inadequate samples.

PMID- 1376507
TI  - Automated purification of canine islets.

PMID- 1376508
TI  - In situ intraductal collagenase injection for preparation of islets of Langerhans
      in the pig.

PMID- 1376509
TI  - FK 506--an effective immunosuppressant in achieving long-term functional islet
      allograft survival in diabetic rats.

PMID- 1376510
TI  - Induction of donor-specific unresponsiveness in rat islet allografts by FK 506.

PMID- 1376511
TI  - A study on the timing of immunologic priming in autoimmune insulitis in NOD mice.

PMID- 1376512
TI  - Effect of FK 506 on human pancreatic islets following renal subcapsular
      transplantation in diabetic nude mice.

PMID- 1376513
TI  - Successful combination therapy with FK 506 and 15-deoxyspergualin in pancreatic
      islet xenografting.

PMID- 1376514
TI  - Successful transplantation of newborn rat intestine as a free graft.

PMID- 1376515
TI  - Cytoimmunologic monitoring of small bowel allograft recipients.

PMID- 1376516
TI  - Effect of FK 506 on graft survival in rat small intestinal allografts.

PMID- 1376517
TI  - Effect of FK 506 on bowel transplantation in rats.

PMID- 1376518
TI  - Intravenous, oral pharmacokinetics, and oral dosing of FK 506 in small bowel
      transplant patients.

PMID- 1376519
TI  - Suppression of the histologic changes of GVHD by FK 506 in rat small bowel
      transplantation.

PMID- 1376520
TI  - Effect of short-term immunosuppressive therapy with FK 506 or CyA on the donor in
      small intestine allotransplantation in rats.

PMID- 1376521
TI  - Effect of FK 506 on orthotopic small bowel transplantation in rats.

PMID- 1376522
TI  - Changes in cell surface markers in human small bowel transplantation with FK 506.

PMID- 1376523
TI  - Management of intestinal transplantation in humans.

PMID- 1376524
TI  - Critical analysis of rejection markers sIL-2R, urinary amylase, and lipase in
      whole-organ pancreas transplantation with exocrine bladder drainage.

PMID- 1376525
TI  - 72-hour preservation of the canine pancreas: successful replacement of
      hydroxyethylstarch by dextran-40 in UW solution.

PMID- 1376526
TI  - Characterization of early graft damage after pancreatic transplantation.

PMID- 1376527
TI  - A method for the evaluation of pancreas graft preservation in dogs by histologic
      surface analysis.

PMID- 1376528
TI  - Ulcer perforation in the grafted duodenal segment following pancreatic
      transplantation--a case report.

PMID- 1376529
TI  - Pancreatic exocrine "burnout" following pancreas transplantation.

PMID- 1376530
TI  - Stimulation of exocrine secretions of pancreatic allograft after
      duodenocystostomy.

PMID- 1376531
TI  - Basic study on immunologic effects of cyclosporine and FK 506 for application to
      pancreatic transplantation.

PMID- 1376532
TI  - The effect of short-term FK 506 therapy on pancreas transplantation using the
      cuff technique in rats.

PMID- 1376533
TI  - Influence of rejection episodes on the relationship between exocrine and
      endocrine function in bladder-drained pancreas transplants.

PMID- 1376534
TI  - Is urinary amylase a reliable index for monitoring whole pancreas endocrine graft
      function?

PMID- 1376535
TI  - Use of atropine for treatment of lindane poisoning in two chickens.

PMID- 1376536
TI  - HIV-1 genomic RNA diversification following sexual and parenteral virus
      transmission.
AB  - Human immunodeficiency virus type 1 (HIV-1) genomic RNA variation was studied in
      seven presumed donor-recipient pairs directly following sexual (6/7) or
      parenteral (1/7) transmission. The first RNA-positive serum sample of each
      recipient and the serum sample of the virus transmitter, identified by
      epidemiological history and taken within a time bracket of three months of the
      recipient seroconversion, were analyzed by polymerase chain reaction
      amplification followed by sequencing of eight cDNA clones of 276 bp, including
      the V3 coding region. The sequence populations of the recipients were without
      exception homogeneous, while the sequence populations of the transmitters showed
      varying degrees of heterogeneity. Nucleotide distance between consensus sequences
      of unrelated individuals from the Amsterdam population (interpatient variation)
      averaged 11% (range 7-15%). The largest distance between two clonal sequences of
      one individual (intrapatient variation) was also 11%. Consensus sequences of five
      recipients differed by only 0-1% from the consensus sequence of the presumed
      transmitter, including two pairs of which the transmission was either proven or
      highly probable. This contrasted with a difference of 10-12% in two pairs,
      casting doubt on the epidemiological relatedness. Antibody reactivity to a panel
      of V3 peptides with varying degrees of similarity to the V3 sequences obtained
      did not augment the discriminatory power of sequence analysis. Results of the
      sequential sequencing of samples of one transmitter suggest that this was due to
      an anamnestic antibody response of the transmitter to early variants. From the
      loss of sequence heterogeneity following transmission and the consensus sequence
      similarities observed within five transmitter-recipient pairs, we conclude that
      HIV-1 transmission results in the selection of a limited number of genomes
      carrying on the infection in the new host, but does not generally lead to a shift
      in the sequence population as defined by the consensus sequence.

PMID- 1376537
TI  - Structural determination of gangliosides that bind to influenza A, B, and C
      viruses by an improved binding assay: strain-specific receptor epitopes in sialo
      sugar chains.
AB  - An improved binding assay for detection of ganglioside receptors for influenza A,
      B, and C viruses was developed. In this system, the virions bound to gangliosides
      that were developed on a silica gel thin-layer plate were detected by mouse
      monoclonal antibody against viral hemagglutinin and peroxidase-conjugated anti
      mouse immunoglobin. No hydrolysis of the gangliosides by viral receptor
      destroying enzyme was detected in the present condition. The reactivity of the
      viruses to gangliosides depended on the amount of developed gangliosides (10
      pmols-10 nmols), the molecular species of sialic acid, and their sugar sequences.
      Human influenza A (PR/8/34), B (Lee/40), and C (Ann Arbor/1/50) viruses bound
      different receptor epitopes of sialo-sugar chains of gangliosides. The A/PR/8
      virus bound most effectively to Neu5Ac-containing lacto-series gangliosides
      carrying type I and type II sugar chains, followed by ganglio-series and
      hematoside-series gangliosides. The A/PR/8 virus weakly bound to Neu5Ac alpha
      2,6lactotetraosylceramide [IV6(Neu5Ac)Lc4Cer] and Neu5Ac alpha 2,6paragloboside
      [IV6(Neu5Ac)nLc4Cer] carrying Neu5Ac alpha 2,6Gal sequence, although their Neu5Ac
      alpha 2,3Gal derivatives were the most potent gangliosides tested. B/Lee/40 bound
      restrictively to IV6(Neu5Ac)Lc4Cer and IV6(Neu5Ac)nLc4Cer, which carry Neu5Ac
      alpha 2,6Gal sequence, and type I and type II lacto-series sugar chain,
      respectively. C/Ann Arbor/1/50 reacted only with 9-O-Ac-Neu5Ac-carrying sugar
      chains in all the gangliosides tested. This method also allowed the microanalysis
      of receptor gangliosides of unknown samples. ESK cells, sensitive to the
      influenza A viruses infection, expressed several kinds of receptor active
      gangliosides, while those from ESK-R cells, resistant to the virus infection,
      were undetectable.

PMID- 1376538
TI  - Mouse hepatitis virus nucleocapsid protein-specific cytotoxic T lymphocytes are
      Ld restricted and specific for the carboxy terminus.
AB  - Infection of mice with the JHM strain of mouse hepatitis virus (MHV) results in
      an acute encephalomyelitis associated with primary demyelination of the central
      nervous system. Efforts at understanding the components of the immune response in
      the development of chronic MHV-induced demyelination have implicated the antibody
      response and both the CD4+ and CD8+ T cell responses. In this report, we
      demonstrate that Balb/c (H-2d) mice immunized with the JHM (JHMV) strain of MHV
      develop a CD8+ cytotoxic T lymphocyte (CTL) response. One population of these
      virus-specific CTL recognize the nucleocapsid (N) protein. Recombinant vaccinia
      viruses expressing either the entire N protein or carboxy-terminal deletions were
      used to determine the number and location of the epitope(s) recognized. The CTLs
      were found to recognize a peptide contained within the carboxy-terminal 149 amino
      acids of the N protein. Analysis of infected cell lines expressing transfected
      major histocompatibility genes demonstrated that the anti-N protein CTLs were
      restricted exclusively to the Ld molecule. These data provide the first
      definition of a MHV-specific CTL response directed to a viral protein and suggest
      that the anti-N protein CTL response is one potential mechanism used by the host
      to clear JHMV from the central nervous system.

PMID- 1376539
TI  - Flow cytometric analysis of African swine fever virus-induced plasma membrane
      proteins and their humoral immune response in infected pigs.
AB  - African swine fever (ASF) virus-induced plasma membrane proteins may contribute
      to the protective immune response against the disease since they can be involved
      in the antibody-mediated lysis of infected cells. In this study we describe the
      regulation of ASF virus-induced plasma membrane protein expression and its
      antibody induction in pigs after viral infection by flow cytometric analysis.
      More than 80% of infected cells contained viral antigens on the surface membranes
      at 6 hr postinfection (hpi), and the relative amount of viral antigen expression
      was increased at 12 and 20 hpi. The kinetics of individual viral protein
      expression on cell surfaces was studied by a collection of monospecific
      antibodies directed against the six viral plasma membrane proteins p12, p15, p16,
      p23.5, p30, and p35. Most of these proteins were expressed at 6 hpi, with the
      exception of p35, which was first detected at 12 hpi. The percentage of cells
      expressing each antigen at different hpi was also determined. The immune response
      against virus-induced plasma membrane proteins in pigs infected with an
      attenuated ASF virus strain was studied. Antibodies against viral epitopes
      exposed on plasma membranes reached a plateau at 20 days postinfection (dpi). The
      relative amount of antibodies induced during infection with these specificities
      was not directly related to the antibody titer of the sera. Sera obtained at 20
      and 40 dpi contained antibodies against most of the viral plasma membrane
      proteins and were most efficient in recognition of viral antigens exposed on the
      surface of infected cells at early times.

PMID- 1376540
TI  - Sulfated polymers inhibit the interaction of human cytomegalovirus with cell
      surface heparan sulfate.
AB  - Several sulfated polysaccharides (dextran sulfate, pentosan polysulfate, heparin)
      and copolymers of acrylic acid with vinylalcohol sulfate have proved to be potent
      inhibitors of human cytomegalovirus (CMV) infectivity in vitro. Sulfated alpha
      cyclodextrins are only weak inhibitors of CMV. A close correlation was found
      between the 50% inhibitory concentrations of the sulfated polymers for CMV
      cytopathogenicity, virus-cell binding, and expression of immediate early antigens
      (IEA) in human embryonic lung (HEL) cells. CMV particles bound specifically to
      heparin-Sepharose. Sulfated polymers specifically eluted the virus particles from
      this matrix. Enzymatic digestion of cell surface heparan sulfate, but not of
      chondroitin sulfate, prevented the cells from being infected with CMV. Moreover,
      radiolabeled CMV bound efficiently to, and were infective for wild-type Chinese
      hamster ovary (CHO) cells, whereas virus binding to, and infection of, mutant CHO
      cell lines that were deficient in either all glycosaminoglycans or heparan
      sulfate only was significantly impaired. The mechanism of action of the sulfated
      polymers can be attributed to an inhibitory effect on the binding of CMV
      particles to the host cells. Presumably, the sulfated polymers interact with the
      viral envelope site(s) involved in the attachment of the CMV virions to cell
      surface heparan sulfate.

PMID- 1376541
TI  - Increased synthesis of polycistronic mRNA associated with increased
      polyadenylation by vesicular stomatitis virus.
AB  - Electron microscopy suggested that the mRNA produced in vitro by tsG16(I), a
      temperature-sensitive mutant of vesicular stomatitis virus, contained an
      increased proportion of polycistronic mRNAs. Using hybrid selection, we found
      that the poly(A)+ mRNA synthesized in vitro by tsG16(I) contained approximately
      two to three times more polycistronic mRNA than did poly(A)+ mRNA synthesized in
      vitro by the parental wild-type (wt) virus. The increase in polycistronic mRNA
      occurred at all intergenic junctions examined. In vitro, tsG16(I) has an
      increased polyadenylation phenotype and a temperature-sensitive transcriptase
      activity that appear to be due to different mutations. Partial revertants of
      tsG16(I), which have lost the aberrant polyadenylation phenotype but retain the
      in vitro thermosensitive transcriptase, produced wt amounts of polycistronic
      mRNA. This suggested that the increased production of polycistronic mRNA by
      tsG16(I) may be associated with the increased polyadenylation phenotype of this
      mutant. These data further support the hypothesis that an increase in size of
      poly(A) tracts is associated with increased production of polycistronic mRNA.

PMID- 1376542
TI  - Location of neutralizing epitopes on the hemagglutinin-esterase protein of
      influenza C virus.
AB  - Neutralization-resistant variants of influenza C/Ann Arbor/1/50 virus were
      selected with monoclonal antibodies against four different antigenic sites on the
      hemagglutinin-esterase (HE) glycoprotein, and their HE genes were sequenced to
      identify amino acid residues important for the integrity of each site. Twelve
      different amino acid substitutions in a total of 18 antigenic variants were all
      located on the HE1 subunit. Although variants for antigenic site A-2 had a change
      at position 367, all substitutions in the variants for sites A-1, A-3, and A-4
      occurred in the central region of the HE1 spanning amino acid positions 178 to
      283. Furthermore, it was found that many of the substitutions in the variants
      selected with antibodies to sites A-1 and A-3 were clustered within or near one
      of the three variable regions revealed previously by comparing amino acid
      sequences of the HEs among various influenza C isolates (Buonagurio, D. A.,
      Nakada, S., Fitch, W. M., and Palese, P., Virology 146, 221-232, 1985). The
      antigenic variants were also examined for their ability to agglutinate chicken
      and human erythrocytes in order to obtain information concerning the receptor
      binding site on the HE molecule. The results suggested that the amino acid
      changes at residues 178, 186, 187, 190, 206, 212, and 226 decreased the
      hemagglutinating activity whereas those at residues 245, 266, and 283 produced an
      opposite effect.

PMID- 1376543
TI  - National Ambulatory Medical Care Survey: 1989 summary.
AB  - Based on data collected from a national sample of office-based physicians,
      statistics are presented on the provision and utilization of ambulatory medical
      care services in physicians' offices during 1989. Ambulatory medical care
      services are described in terms of patient characteristics, physician practice
      characteristics, and visit characteristics. A summary of trends in office-based
      ambulatory medical care from 1975-89 is included.

PMID- 1376544
TI  - [The value of palliative colorectal surgery].

PMID- 1376546
TI  - [What therapeutic benefits are there in the early diagnosis of metastases in
      patients with breast carcinoma?].
AB  - Early detection and curative treatment of metastasis of breast cancer is seldom.
      Local surgery and radiation could be helpful. The survival time was sometimes not
      a psychological advantage for the patients with early detection of metastasis.

PMID- 1376545
TI  - [Locoregional chemotherapy in the treatment of liver metastasis of breast
      carcinoma].
AB  - Locoregional chemotherapy enables specific treatment of organ metastases by using
      a dosage of medication that is maximally effective but only has minimal side
      effects on other organs. Since 1983, we have applied this procedure in patients
      whose liver represented the only target-organ of metastases. Between 1983 and
      1990, locoregional chemotherapy was performed in 59 women suffering from liver
      metastases of breast cancer. The average age of our patients was 52 years. 4
      patients were treated for solitary metastases that could not be resected, in 5
      patients the infiltration of hepatic parenchyma with metastases accounted to 25%,
      in 32 patients hepatic infiltration ranged between 25% and 75% and in 18 patients
      it surpassed 75%. In 39% of our patients, a partial remission occurred. The mean
      period of survival after beginning of treatment was 149 days, whereas the longest
      survival time lasted 1009 days. We conclude that the locoregional chemotherapy,
      destined for treatment of liver-metastases of breast cancer, with a mean survival
      time of only five months could insufficiently satisfy our expectations.
      Therefore, a decision to administer such palliative therapy should be made on an
      individual basis. In our opinion, one indication represents solitary metastases
      that are not resectable, a further indication is pain due to expansion of the
      liver capsule because of diffuse metastases.

PMID- 1376547
TI  - Contribution of cell culture to the study of the physiology of the stria
      vascularis and Reissner's membrane.
AB  - Cell culture is a well-established tool in cell biology which may overcome the
      limitations of the experimental methods currently used to investigate the
      physiology of labyrinthine fluids. Using explant and dissociated cell culture
      technique, sheets of oriented cells derived from the stria vascularis and
      Reissner's membrane may be obtained, which allows new experimental approaches
      such as the patch-clamp technique. Other experimental approaches are considered
      which might improve our understanding of inner ear physiology.

PMID- 1376548
TI  - [Proceedings of the international symposium on ion channels and calcium
      antagonists (ISICCA). 1991 September 26-28 Shanghai Medical University, Shanghai,
      China. Abstracts].

PMID- 1376549
TI  - Inhibition of nitric oxide synthase causes excitation of the circular muscle in
      rat distal colon.

PMID- 1376550
TI  - Alterations of spinal dorsal horn substance P following electroacupuncture
      analgesia--a study of the formalin test with immunohistochemistry and
      densitometry.
AB  - Substance P (SP), released from thin afferent terminals, is believed to be a
      neurotransmitter for pain transmission in the spinal dorsal horn. It has been
      demonstrated that in addition to analgesia, morphine increases the accumulation
      of SP possibly due to the inhibition of its release. The present work
      investigated the level of spinal SP like immunoreactivity (SPLI) following
      electroacupuncture analgesia in rats using immunohistochemistry and image
      analysis. Experiment results revealed that formalin injected into the hind paw
      elicited marked pain response and accumulation of SP in the spinal dorsal horn.
      Electroacupuncture of Tsu-San-Li could depress the pain response, however
      increasing further the SP accumulation. It is thus suggested that pain
      stimulation itself may activate the endogenous opioid mechanism to inhibit SP
      release and acupuncture is able to enhance the process. This may be one mechanism
      of acupuncture analgesia.

PMID- 1376551
TI  - Topics in clinical pharmacology: filgrastim, a myeloid colony stimulating factor.
AB  - Filgrastim (granulocyte colony stimulating factor) recently became commercially
      available for the treatment of chemotherapy-induced neutropenia. Studies have
      shown that filgrastim induces a dose-dependent granulocytosis in humans, thereby
      shortening the period of neutropenia in patients treated conventionally with
      submarrow ablative doses of chemotherapy, as well as with marrow ablative therapy
      given in the bone marrow transplant setting. By reducing the incidence and
      severity of infections and mucositis in patients treated with chemotherapy, it
      has a significant economic impact since it shortens the duration of antibiotic
      administration and hospitalization. Adverse reactions reported are limited to
      mild to moderate bone pain. Several other potential applications are being
      investigated for filgrastim, including treatment of patients with myelodysplastic
      syndrome and congenital neutropenia.

PMID- 1376552
TI  - Monosomy 18q12.1----21.1: a recognizable aneuploidy syndrome? Report of a patient
      and review of the literature.
AB  - This report of a patient with an interstitial deletion 18q and review of
      previously described cases suggest a clinically recognizable syndrome. The
      phenotype appears to result from a microdeletion of part of 18q12.2 or q12.3, or
      a deletion of parts of both bands.

PMID- 1376553
TI  - New variant in exon 3 of the proteolipid protein (PLP) gene in a family with
      Pelizaeus-Merzbacher disease.
AB  - A C--greater than G transversion has been found in exon 3 of the PLP gene of
      affected males and their mother in a single sibship with Pelizaeus-merzbacher
      disease (PMD). The transversion should not result in an amino acid change in the
      protein but it does result in the loss of a HaeIII restriction endonuclease
      cleavage site. It is concordant with the disease in this family. One-hundred-ten
      unrelated X chromosomes are negative for this mutation. No other sequence defect
      was found in the PLP exons of the affected males. The cause of disease in this
      family remains unknown, but the association between this rare mutation and PMD is
      intriguing. The mutation can serve as a marker for following segregation of the
      PLP gene.

PMID- 1376554
TI  - Immunolocalization of a glycosylphosphatidylinositol-specific phospholipase D in
      mast cells found in normal tissue and neurofibromatosis lesions.
AB  - A large number of eukaryotic proteins have been shown to be anchored to the cell
      membrane by glycosylphosphatidylinositol (GPI). This glycolipid anchor can serve
      as a substrate for anchor-specific phospholipases that convert the GPI-anchored
      membrane proteins into soluble forms. Soluble forms of many GPI anchored proteins
      have been identified in vivo in connective tissue, plasma, and urine. The authors
      have discovered that mammalian plasma contains a GPI-specific phospholipase D
      (GPI-PLD). Because it recognizes a portion of the conserved glycan core
      structure, all GPI-anchored proteins are potential substrates. The authors report
      the development of a murine monoclonal antibody specific for one form of the
      human GPI-PLD and the immunohistochemical localization of this enzyme to mast
      cells.

PMID- 1376555
TI  - Post-transplant recurrent hepatitis B viral liver disease. Viral-burden,
      steatoviral, and fibroviral hepatitis B.
AB  - Recurrence of hepatitis is a well-documented complication of hepatitis B liver
      disease, post-transplantation. It is well established also that the earliest
      hepatocellular change is the appearance of hepatitis B viral (HBV) markers and
      that the disease is rapidly progressive. In this article on 17 liver transplants
      in 16 HBV positive patients with long-term follow-ups (100-1234 days), the
      distinctive pathologic features of this disease are emphasized: the extreme viral
      load, the steatosis, and/or fibrosis. An attempt to quantitate the magnitude of
      the viral burden was made and the result was a staggering figure. In one patient,
      an estimated 10(18) HBV core particles were present in the liver. One of two
      patterns of progression were noted. In four patients in addition to the massive
      nuclear hepatitis B core antigen (HBcAg) and cytoplasmic hepatitis B surface
      antigen (HBsAg) positivity, superimposed hepatitic changes led to diffuse hepatic
      fibrosis (fibroviral hepatitis B); and in another six patients, extraordinary
      hepatocellular viral marker positivity and steatosis were the hallmarks
      (steatoviral hepatitis B). Steatosis is not usually considered a feature of HBV
      liver pathology. These results suggest that more than one type of posttransfusion
      recurrent hepatitis B liver disease exists pathologically.

PMID- 1376556
TI  - Follicular lymphomas of the gastrointestinal tract. Pathologic features in 31
      cases and bcl-2 oncogenic protein expression.
AB  - The gastrointestinal tract is the most common site for extranodal lymphomas, but
      follicular lymphomas involving the gut are rare. To study their pathologic
      features and bcl-2 expression, 31 follicular lymphomas of the GI tract were
      reviewed and unstained paraffin sections from 24 of the cases were
      immunohistochemically stained using a monoclonal antibody for the peptide product
      of the proto-oncogene bcl-2. The most common site of lymphoma involvement was the
      small intestine, especially the terminal ileum. Gastric lymphomas tended to
      present clinically with symptomatic ulcers and small intestinal lesions presented
      with obstruction. Five cases involving the terminal ileum or colon had a gross
      appearance of multitudinous mucosal polyps and were considered to represent
      examples of "multiple lymphomatous polyposis." Enhanced expression of the bcl-2
      oncogenic protein was detectable in lymphoma cells in 75% of cases and at lower
      levels in normal lymphoid cells in most cases. Small cleaved or mixed cell
      lymphomas were more likely to show enhanced expression than were large cell
      cases. Reactive germinal centers showed no bcl-2 staining. It is concluded that
      follicular GI lymphomas are associated with distinctive pathological features. In
      their tendency to express bcl-2, these neoplasms resemble their lymph node-based
      counterparts. Immunohistochemical staining for enhanced bcl-2 expression is of
      potential diagnostic utility in distinguishing between follicular lymphoma and
      follicular lymphoid hyperplasia in the gastrointestinal tract. The relevance of
      the results to lymphoma of mucosa-associated lymphoid tissue (MALT) is discussed.

PMID- 1376557
TI  - Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1,
      and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix
      formation and cessation of repair.
AB  - Recombinant platelet-derived growth factor (BB homodimer, rPDGF-BB), transforming
      growth factor beta 1 (rTGF-beta 1), and basic fibroblast growth factor (rbFGF)
      can accelerate healing of soft tissues. However, little information is available
      characterizing the components of wound matrix induced by these growth factors and
      the molecular mechanisms underlying accelerated repair and wound maturation. In
      this study, the composition, quantity, and rate of extracellular matrix
      deposition within growth factor-treated lapine ear excisional wounds were
      analyzed at different stages of healing using specific histochemical and
      immunohistochemical stains, coupled with image analysis techniques. Single
      application of optimal concentrations of each growth factor accelerated normal
      healing by 30% (P less than 0.0003); rPDGF-BB markedly augmented early
      glycosaminoglycan (GAG) and fibronectin deposition, but induced significantly
      greater levels of collagen later in the repair process, compared with untreated
      wounds rTGF-beta 1 treatment led to rapidly enhanced collagen synthesis and
      maturation, without increased GAG deposition. In contrast, rbFGF treatment
      induced a predominantly angiogenic response in wounds, with a marked increase in
      endothelia and neovessels (P less than 0.0001), and increased wound
      collagenolytic activity (P less than 0.03). rbFGF-treated wounds did not evolve
      into collagen-containing scars and continued to accumulate only provisional
      matrix well past wound closure. These results provide new evidence that growth
      factors influence wound repair via different mechanisms: 1) rPDGF-BB accelerates
      deposition of provisional wound matrix; 2) rTGF-beta 1 accelerates deposition and
      maturation of collagen; and 3) rbFGF induces a profound monocellular angiogenic
      response which may lead to a marked delay in wound maturation, and the possible
      loss of the normal signal(s) required to stop repair. These results suggest that
      specific growth factors may selectively regulate components of the repair
      response by differing mechanisms, offering the potential for targeted therapeutic
      intervention.

PMID- 1376558
TI  - Phagocytosis and deposition of vascular beta-amyloid in rat brains injected with
      Alzheimer beta-amyloid.
AB  - The presence of extracellular deposits of beta-amyloid protein in the brain is a
      hallmark of Alzheimer's disease (AD). In an effort to determine the effect of
      amyloid in an animal model, the authors injected amyloid cores isolated from AD
      brains into the cortex and hippocampus of rats. Lipofuscin, a major contaminant
      of the plaque core preparation, was injected on the contralateral side and used
      as a control to induce an analogous phagocytic cell response. Rats were
      sacrificed 2 days, 7 days, and 1 month after injection and amyloid located by
      four histochemical techniques. Amyloid and lipofuscin move from the site of
      injection into otherwise undamaged neuropil, persist for at least 1 month and are
      both associated with increases in glial fibrillary acidic protein and microglia
      (OX-42) staining. By 1 week, many of the amyloid cores are ingested by
      phagocytes. Some of the beta-amyloid-containing phagocytes migrate to the vessels
      and to the ventricles, and by 1 month, a significant amount of the amyloid is
      directly associated with the vessels. This suggests that phagocytic cells can
      internalize exogenous amyloid and attempt to clear it from the central nervous
      system (CNS). Therefore, the observed distribution of amyloid is not necessarily
      the initial site of deposition.

PMID- 1376559
TI  - The sequential development of abnormal prion protein accumulation in mice with
      Creutzfeldt-Jakob disease.
AB  - The distribution and sequential development of prion protein (PrP) accumulation
      in the central nervous system (CNS) and non-neuronal organs of mice infected with
      Creutzfeldt-Jakob disease (CJD) were investigated immunohistochemically using a
      new pretreatment method that greatly enhanced the immunoreactivity of PrP. Prion
      protein accumulation in the CNS was first detected at 30 days after inoculation
      and then developed near the inoculation site or periventricular area, and later
      spread to the whole cerebrum and then to the pons. Its staining took some
      characteristic forms. Among non-neuronal organs, PrP accumulated in the
      follicular dendritic cells (FDCs) in spleen, lymph node, Peyer's patch, and
      thymus. FDCs staining appeared in spleen, lymph node, and Peyer's patch at 21 or
      30 days after inoculation, and in thymus at 90 days. Germinal centers developed
      in the thymus of some CJD-infected mice. No PrP staining was detected in any
      examined organs of age-matched control mice.

PMID- 1376560
TI  - Simian virus 40-induced disease in rhesus monkeys with simian acquired
      immunodeficiency syndrome.
AB  - Simian virus 40 (SV40) disease was diagnosed in four rhesus monkeys that died
      with SIV-induced acquired immunodeficiency syndrome (AIDS). One juvenile monkey
      seroconverted for SV40 6 months after inoculation with SIV and developed severe
      bilateral tubulointerstitial nephritis. In contrast, progressive multifocal
      leukoencephalopathy (PML) occurred in two adult monkeys that were seropositive
      for SV40 before SIV inoculation, as well as a third adult that was naturally
      infected with SIV and seropositive for SV40 5 years before death. Large
      intranuclear inclusions containing abundant polyomavirus particles were limited
      to either renal tubular epithelial cells or oligodendrocytes. In situ DNA
      hybridization for SV40 large T antigen further demonstrated that SV40 nucleic
      acid was localized to either kidney or brain tissue. By immunohistochemical
      analysis, areas of central nervous system inflammation and demyelination were
      shown to contain CD68+ macrophages (gitter cells), aggregates of CD8+ T
      lymphocytes, and numerous gemistocytic astrocytes that labeled for glial
      fibrillary acidic protein. These observations indicate that rhesus monkeys with
      SIV-induced AIDS are predisposed to polyomaviral disease, in which SV40 nucleic
      acid is observed in renal tissue in primary infections and brain tissue after
      viral reactivation. Furthermore, this organ-specific replication suggests that
      tissue-tropic strains of SV40 may develop in immunodeficient monkeys.

PMID- 1376561
TI  - Mutated c-Ha-ras oncogene alters cytokeratin expression in the human breast
      epithelial cell line MCF-10A.
AB  - MCF-10A, a spontaneously immortalized human breast epithelial cell line, has been
      transformed by transfection with the mutated c-Ha-ras oncogene obtained from T24
      carcinoma cells. The pattern of cytokeratin expression was studied in MCF-10A
      cells in comparison with plasmid transfected or MCF-10Aneo cells, normal ras
      proto oncogene transfected or MCF-10AneoN cells, and transformed or MCF-10AneoT
      cells. Cytokeratin expression was studied by western immunoblot of total cellular
      proteins separated by two-dimensional gel electrophoresis. Blots with cytokeratin
      specific AE1 and AE3 antibodies showed identical molecular weight species of
      cytokeratins in MCF-10A, MCF-10Aneo, MCF-10AneoN, and MCF-10AneoT cells; however,
      in MCF-10AneoT cells, the intensity of immunostaining and the number of
      immunoreactive phosphorylated polypeptides keratins 7, 8, 15, and 16 was
      decreased. It was concluded that c-Ha-ras oncogene-induced transformation alters
      quantitatively the cytokeratin pattern of human breast epithelial cells and that
      these changes could explain some of the morphologic alterations observed in c-Ha
      ras transformed cells.

PMID- 1376562
TI  - Cell death in cranial neural crest development.
AB  - The rhombencephalic neural crest, crucial to the patterning and development of
      many craniofacial structures, migrates laterally from the dorsal hindbrain, but
      not as a continuous sheet. We have used a vital dye to demonstrate a
      discontinuous pattern of cell death in the dorsal midline of the avian
      rhombencephalon associated with the migration of the neural crest. Whilst cell
      death commences in the dorsal midline of the presumptive mesencephalon at stage
      8, two distinct domains of cell death are apparent in the rhombencephalon by
      stage 11. The rostral domain lies over primary rhombomere RhA1 and rhombomere
      rh3, while the caudal domain occurs on the neural midline between the otic
      vesicles, in the region of rh5. Using a marker for the neural crest, we show that
      the rostral and caudal domains of cell death correlate with the absence of neural
      crest migration from rh3 and rh5. Thus segment-specific cell death in the dorsal
      region of particular rhombomeres may account for their subsequent failure to
      contribute to the cranial neural crest.

PMID- 1376563
TI  - Differentiation of bursal secretory-dendritic cells studied with anti-vimentin
      monoclonal antibody.
AB  - Embryonic and posthatched differentiation of bursal secretory dendritic cells,
      which express vimentin intermediate filaments, were studied with anti-vimentin
      (clone 3B4) and anti-cytokeratin (clone Lu5) monoclonal antibodies. Anti
      cytokeratin staining revealed that medullary reticular epithelial cells formed a
      continuous network at every age, whereas the vimentin positive cells were single
      and showed dendritic appearance. On the basis of location, number, shape,
      polarized appearance, and Ia staining, the vimentin-positive cells and secretory
      dendritic cells appeared to be the same cell. Secretory dendritic cell precursors
      entered the bursal epithelium between 11 and 13 days of embryogenesis. The first
      vimentin positive cell appeared in the bud of 14-day embryos. Bud formation
      preceded the appearance of vimentin-positive cells. These observations suggested
      that the secretory dendritic cell precursor did not express vimentin when it
      entered the epithelium. Between 15 days of embryogenesis and 2 weeks of posthatch
      development, the changes in vimentin staining pattern revealed a cytological
      differentiation of the vimentin-positive cell. During rapid bursal growth, the
      number of secretory dendritic cells (vimentin-positive cells) increased about 18
      times possibly by proliferation of vimentin-negative precursors in the epithelial
      arches of the corticomedullary border.

PMID- 1376565
TI  - [The palliative surgery of esophageal cancer].

PMID- 1376564
TI  - Histochemical study of the heart of the axolotl (Ambystoma mexicanum).
AB  - We have investigated the presence of cells containing monoamines, substance P,
      and neuron-specific enolase (NSE) in the heart and in the pericardial wall of a
      urodele amphibian, the axolotl. Fibers containing substance P-like
      immunoreactivity were present in the heart but not in the pericardial wall. Also
      present in the heart were small branched cells, which stained metachromatically
      with toluidine blue. Similar cells were found in the peritoneum and were
      tentatively identified as mast cells. NSE-immunoreactive fibers were found both
      in the heart and in the pericardial wall. Small intensely fluorescent (SIF) cells
      of the pericardial wall contained a high concentration of norepinephrine but no
      other monoamines, substance P, or NSE. Comparison with data available for the
      mudpuppy, Necturus maculosus, a closely related amphibian species, suggests that
      the innervation of the heart in the axolotl is substantially different.

PMID- 1376566
TI  - [Adenocarcinoma of Barrett's epithelium].

PMID- 1376567
TI  - The effect of substance P on neutrophil function in normal and asthmatic
      subjects.

PMID- 1376568
TI  - In vitro effects of substance P and somatostatin on lymphoproliferation in
      rainbow trout (Salmo gairdneri).
AB  - Lymphocytes from peripheral blood of rainbow trout are put in the presence of
      increasing concentrations of substance P (SP) and somatostatin (SOM). We have
      shown that SP stimulates and SOM inhibits lymphoproliferation and that the
      effects are dose dependent. These results suggest that SP and SOM receptors may
      exist on fish peripheral blood lymphocytes. When cells are stimulated by PHA or
      LPS, the presence of SP enhances the response to PHA whereas it only modifies the
      response to LPS to a slight extent. The presence of SOM inhibits PHA- or LPS
      induced stimulation. The inhibition of the proliferation is higher in the case of
      LPS-stimulated cells. These results suggest that there is an unequal distribution
      of neuropeptide receptors among the various lymphocyte subpopulations.

PMID- 1376569
TI  - Ion channel activity and transmembrane signaling in lymphocytes.
AB  - Transmembrane signalling refers to the process of transfer of information from
      the extracellular world into the intracellular space. The information is
      transduced through several possible pathways. The significance of cell surface
      dynamics, ion channel activity and drug effects are discussed in the signal
      transmission, with special reference to Na+ channels and the Ca2+ sensitive
      potassium channels.

PMID- 1376570
TI  - The apparent lack of cell cycle dependency for substance P binding to murine
      lymphocytes.

PMID- 1376571
TI  - Beta-endorphin 1-17 modulates high affinity IL-2 receptor expression on human T
      cells.

PMID- 1376572
TI  - Anti-myelin basic protein autoantibodies in rats stressed by overcrowding.

PMID- 1376573
TI  - Expression of the natural killer (NK) cell-associated antigen CD56(Leu-19), which
      is identical to the 140-kDa isoform of N-CAM, in neural and skeletal muscle cells
      and tumors derived therefrom.

PMID- 1376574
TI  - Distribution of Leu-19(CD56) natural killer lymphocyte antigen in cultured cells
      from the human embryonic central nervous system.

PMID- 1376575
TI  - Hydrocortisone modulates cytokeratin and extracellular matrix expression by the
      thymic microenvironment.

PMID- 1376576
TI  - [Wegener's granulomatosis with prostatic involvement].

PMID- 1376577
TI  - Management of accidental kerosene ingestion.
AB  - Accidental kerosene ingestion is still a common problem in Libya. It causes
      considerable morbidity and occasionally mortality. The role and choice of
      antibacterial agents in its management remain unsettled. Pulmonary damage has
      been reported as resulting from aspiration. In aspiration pneumonia, anaerobic
      organisms may be important pathogens and metronidazole may have a place in
      therapy. The present randomized trial in 100 children with accidental kerosene
      ingestion assesses the role of ampicillin, carbenicillin and metronidazole in its
      management. The results are not conclusive but chemoprophylaxis appears to
      decrease morbidity. Of the various regimens used, the ampicillin/metronidazole
      combination was found to be slightly better than the others. Further study is
      recommended.

PMID- 1376578
TI  - Maternal and environmental factors associated with infections and undernutrition
      in young Australian aboriginal children.
AB  - Forty-eight Aboriginal infants in remote communities in north-west Australia were
      studied monthly from birth to 2 years. Birthweight and growth were positively
      associated with maternal health during pregnancy, regular antenatal supervision
      and lack of drinking alcohol or smoking tobacco as well as with personal and
      family hygiene. Impaired growth was associated with families which had more
      expensive consumer goods such as televisions, air conditioners, video cassette
      recorders and cassette tape players. Most children had impaired growth or frank
      failure to thrive which was associated with high rates of infections,
      particularly of the respiratory and gastro-intestinal tracts, and high rates of
      hospitalization.

PMID- 1376579
TI  - Intussusception in children under 2 years of age in the State of Qatar : analysis
      of 67 cases.
AB  - Intussusception is one of the leading causes of bowel obstruction in early
      infancy and childhood. From 1984-1989, 67 patients under 2 years of age with
      intussusception were diagnosed and treated in our institution. There were 48 boys
      and 19 girls ranging in age from 2 months to 2 years with a mean of 7.4 months.
      Presenting symptoms and signs included abdominal pain (96%), vomiting (93%),
      rectal bleeding (60%) and a palpable mass (67%). Symptoms and signs were present
      for less than 24 hours in about 80% of cases. Most of the intussusceptions were
      of the ileocolic type (75%). The overall success rate of hydrostatic barium enema
      reduction was 49%. The highest rate of reduction by enema was among patients
      between 9 and 16 months of age (83%). The success rate of barium enema reduction
      was negligible after 24 hours of cardinal symptoms. Five children underwent
      surgical exploration without contrast studies because of delayed presentation and
      signs of an acute abdomen. A pathological lead point was found in only four
      cases, the commonest being Meckel's diverticulum. The average length of
      hospitalization was 2.57 days after barium enema reduction and 7.55 days after
      surgical reduction. There were no deaths. There was no case of perforation during
      enema reduction. Three children had recurrence within 3 months of initial
      presentation. The best outcome is associated with early diagnosis and barium
      enema reduction, or selected surgical intervention when indicated.

PMID- 1376580
TI  - Irrational speech occurring in the course of anti-tuberculous therapy--possibly
      caused by isoniazid.
AB  - Two girls, both aged 11 years, one with pulmonary tuberculosis and the other with
      abdominal tuberculosis, were admitted to the Wesley Guild Hospital, Ilesha,
      Nigeria during the months of June and October, respectively, in 1989. During the
      course of treatment with combination chemotherapy, both developed irrational
      speech which responded to temporary withdrawal of isoniazid from the combination.
      Subsequent progress was uneventful.

PMID- 1376581
TI  - Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations
      in children with kwashiorkor in the acute stage and during refeeding.
AB  - Plasma zinc, copper, selenium, ferritin and whole blood manganese concentrations
      were measured in 22 children with kwashiorkor on admission to hospital and on
      days 5, 10 and 30 of refeeding. Twenty similarly aged, healthy, well nourished
      children served as controls. The mean (SEM) zinc, copper and selenium
      concentrations of 7.5 (0.93), 10.8 (0.64) and 0.29 (0.02) mumol/l, respectively,
      in the children with kwashiorkor on admission were all significantly lower than
      the values of 13.7 (0.66), 25.6 (1.72) and 0.72 (0.04) mumol/l in the controls.
      In contrast, the erythrocyte manganese level of 1.67 (0.09) micrograms/gHb and
      the median ferritin concentration of 293 micrograms/dl were significantly higher
      than in the controls. After 30 days there was full clinical recovery with
      significant weight gain and a return of the plasma albumin, caeruloplasmin,
      copper and ferritin to normal. However, manganese remained elevated and zinc and
      selenium concentrations remained significantly low. Our results suggest that
      nutritional rehabilitation of children with kwashiorkor is incomplete by 30 days
      and cannot be judged purely by a return of the plasma proteins to normal.
      Addition of selected trace elements to the diet may hasten full recovery.

PMID- 1376582
TI  - The prevention of Indian childhood cirrhosis.
AB  - Previous studies have led to the hypothesis that the gross hepatic copper storage
      characteristic of Indian childhood cirrhosis (ICC) is due to the early
      introduction of animal milk feeds which have been contaminated with copper from
      brass household utensils. Amongst the families of 100 cases of ICC, the incidence
      of ICC in children born after dietary advice had been given (1/86) was
      significantly lower than in older siblings (12/125). This study attempted to
      document the incidence of ICC and the usage of brass before and after an
      intervention programme in Pune District advising against this pattern of infant
      feeding. The study encountered numerous difficulties in data gathering, but
      documented a fall in ICC prevalence resulting in its virtual disappearance in
      Pune District. This contrasted with an unchanged incidence in Chandigarh.
      Although a fall in brass usage was seen in Pune District, this was actually a
      spontaneous sociological change rather than a result of health education.

PMID- 1376583
TI  - Poisoning from henna dye and para-phenylenediamine mixtures in children in
      Khartoum.
AB  - Poisoning by a mixture of henna dye and para-phenylenediamine dyes led to the
      hospitalization of 31 Sudanese children between 1984 and 1989. There was a
      characteristic clinical presentation. All children presented with an acute and
      severe angioneurotic oedema and 15 of the cases required emergency tracheostomy
      for respiratory obstruction. Acute renal failure occurred in five children who
      recovered after peritoneal dialysis. Mortality was high, all 13 deaths occurring
      within 24 hours of presentation. Hypotensive shock gave a poor prognosis. It is
      possible that similar cases may be occurring unrecognized where henna is
      traditionally used. A programme of public education and restriction of para
      phenylenediamine is urgently required in The Sudan and other affected nations.
      Ingestion was accidental in 12 children, deliberate in 10 and homicidal in three
      cases. Cutaneous absorption was likely in the remaining six.

PMID- 1376584
TI  - The use of herbal remedies in Jamaica.
AB  - A survey of paediatric inpatients at the Tropical Metabolism Research Unit in the
      University Hospital, Kingston, Jamaica demonstrates that 71% had been treated
      with herbal remedies before their presentation to the medical services. The risks
      of the high prevalence of such medication in children are outlined, and two
      remedies in particular are highlighted because of their potential toxicity.

PMID- 1376585
TI  - Hepatotoxicity of high dose salicylate therapy in acute rheumatic fever.
AB  - Liver function tests, including serum alanine aminotransferase (ALT) activity,
      serum bilirubin, alkaline phosphatase, serum proteins, blood ammonia levels and
      intravenous glucose utilization, were monitored in 50 children with acute
      rheumatic fever receiving anti-rheumatic doses of aspirin. There was a
      significant increase in blood ammonia levels and serum ALT after aspirin therapy.
      A significant fall in glucose utilization coefficient was also recorded. Serum
      alkaline phosphatase, bilirubin and total proteins did not change significantly.
      Twenty-two of the 50 children recorded a rise in serum ALT; in 12, the rise was
      five- to tenfold. These 12 children developed adverse symptoms to aspirin. Also,
      all had a marked rise in blood ammonia levels. The children improved clinically
      and biochemically on withdrawal of aspirin. There was no constant relationship
      between hepatocellular function and serum salicylate levels.

PMID- 1376586
TI  - Limited impact of a targeted food supplementation programme in Bangladeshi urban
      slum children.
AB  - An energy-dense supplementary food, together with nutrition education, was given
      to a group of moderately malnourished children aged 6-12 months in a poor slum
      community of urban Bangladesh. An age- and sex-matched control group received
      only nutrition education. Both groups were followed monthly with respect to
      weight gain and morbidity. The purpose of the study was to assess the
      differential impact of a targeted supplementary feeding programme with nutrition
      education and a nutrition education programme alone on monthly weight gain during
      6 months. During the 1st 3 months of the intervention, the monthly weight gain of
      the supplemented children was 205 g vs 159 g in the control children (p less than
      0.05). In the following 3 months, differences in weight gain were no more
      significant. Several possible explanations for this transient impact are
      discussed. It is suggested that nutrition education in the control group may have
      been responsible for the limited difference between the two groups, but seasonal
      and epidemiological factors may also have played a part.

PMID- 1376587
TI  - Efficacy of a therapeutic feeding centre evaluated during hospitalization and a
      follow-up period, Tahoua, Niger, 1987-1988.
AB  - Between 1 February 1987 and 31 May 1988 an evaluation of a nutritional
      rehabilitation centre in Tahoua, Niger was conducted. Among the 381 children
      admitted to the centre, 61 (16%) had kwashiorkor and 347 (91.3%) were aged
      between 6 and 29 months. Recovery and death rates were 46.2% and 14.4%,
      respectively. The median duration of stay until recovery was 21 days. Sixty-two
      per cent of deaths occurred during the 1st week of hospitalization. Three risk
      factors for death were identified by the study: patients with kwashiorkor with a
      weight/height (W/H) less than -3 SD, those with marasmus with a W/H less than -5
      SD, and those dehydrated with marasmus. Among children included in the follow-up
      study after leaving the centre, the risk of dying during the follow-up period
      among children who absconded was 7.1 times higher than the risk observed among
      children who recovered. Among the children who recovered, no relapse was observed
      3-18 months after they left the centre. This investigation indicates the
      importance of intensive therapeutic feeding centres in areas with a high
      prevalence of malnutrition.

PMID- 1376588
TI  - Physical activity and anthropometric and functional characteristics of mildly
      malnourished Senegalese children.
AB  - This study examines the effects of chronic malnutrition on the functional
      capacities and physical activity patterns of a group of 100 healthy Senegalese
      children between the ages of 10 and 13 years. Anthropometric measurements, a sub
      maximal step test, spirometric tests and testing of four motor skills (foot
      races, jumping, throwing, gripping) were conducted and their physical activity
      was monitored by recording of heart rate every minute for 6 hours. The weights of
      two-thirds of these children fell below -1 SD from the WHO/NCHS* norm for their
      ages, their test results were inferior to those of Western children, and the
      level of their physical activity appeared also to be low. When these children are
      divided on the basis of weight deficits for age into well nourished and
      malnourished groups, malnourished children register poorer functional
      performances than well nourished children, but no difference exists with respect
      to the intensity of physical activity. These results highlight the negative
      effect of malnutrition on children's physical performance. The consequences are
      disturbing as the subsistence in the Sahelian Region depends on substantial
      physical labour.

PMID- 1376590
TI  - Concentration of zinc, copper and metallocalorie ratio in bottle-milks prepared
      by poor urban families.
AB  - The concentration of zinc and copper and metallocalorie ratios were measured in
      samples of bottle-milks fed to infants from a poor urban settlement in Brasilia,
      Brazil. The bottle-milks fed to infants under 1 year of age from a sample of 40
      families were analysed for zinc and copper. Zinc and copper concentrations ranged
      from 0.7 to 11.5 mg/l (mean 3.37) and from 0.09 to 1.47 mg/l (mean 0.43),
      respectively. The mean metallocalorie ratio was 1.26 mg/MJ (5.29 mg/1000 kcal)
      for zinc and 0.17 mg/MJ (0.73 mg/1000 kcal) for copper. Based on minimum
      recommendations for formulae, 55% of the bottle-milks had both zinc and copper
      concentrations below 3.2 and 0.4 mg/l, respectively. However, owing to added
      sugar and high caloric concentrations in the milk preparations, metal:calorie
      ratios were below the minimum recommendations in 72.5 and 62.5% of cases for zinc
      and copper, respectively. The variation in zinc and copper concentrations in the
      milks prepared by mothers/infant caretakers under unsupervized home conditions is
      wide. Owing to the low availability of zinc in cow's milk preparations, it is of
      concern that more than half the bottle preparations had zinc and copper
      concentrations/ratios below the minimum recommendations.

PMID- 1376589
TI  - Vitamin A status of young Gambian children: biochemical evaluation and
      conjunctival impression cytology.
AB  - A pilot study was conducted to examine the vitamin A status of Gambian pre-school
      children by conventional biochemical means and to evaluate the use of
      conjunctival impression cytology (CIC) in the detection of subclinical vitamin A
      deficiency. Children were examined on three occasions to coincide with periods of
      low and high carotene intakes. Plasma retinol and beta-carotene showed highly
      significant seasonal changes that reflected the seasonal fluctuations in dietary
      vitamin A. A high prevalence of low plasma retinol levels suggested that vitamin
      A deficiency may be a public health problem in this community. Underlying
      infection and vitamin A instability may have contributed to the low plasma
      retinol levels and given an overestimate of the prevalence of vitamin A
      deficiency. Seasonal changes in conjunctival impression cytology were not
      significant. Abnormal CIC results showed no clear association with plasma beta
      carotene or retinol.

PMID- 1376591
TI  - Evaluation of urinary tract infection in malnourished black children.
AB  - Urinary tract infection (UTI) is a well recognized complication in malnourished
      children. The need to investigate these patients for underlying renal pathology
      has not been clearly defined. Seventy-five children with malnutrition were
      evaluated for UTI by culture of urine obtained suprapubically prior to antibiotic
      therapy. All patients with UTI were investigated with renal ultrasonography,
      intravenous pyelography (IVP) and voiding cystourethrography (VCU). Haemoglobin,
      white cell count, serum urea, creatinine and electrolytes were determined in all
      the children. The mean age of the children was 15.5 months (range 3-60 months).
      UTI was diagnosed in 26 (34.7%), of whom 21 (81%) were boys. The overall
      prevalence of UTI in those with kwashiorkor/marasmic kwashiorkor was 42%.
      Escherichia coli was the organism most commonly cultured (84.6%). Renal
      sonography, IVP and VCU were normal in all infected cases and vesicoureteric
      reflux was not detected in any. This study confirms the high prevalence of UTI in
      malnourished children. As no anatomical abnormalities were demonstrated in the
      patients with UTI, imaging of the renal tract other than real sonography does not
      appear to be indicated in the malnourished child in a first episode of UTI with
      normal renal function.

PMID- 1376592
TI  - A study on delayed hypersensitivity to rotavirus in infancy and childhood.
AB  - The T-cell responsiveness to rotavirus antigen and phytohaemagglutinin (PHA)
      together with T-cell total and subsets quantitation was carried out in 50 non
      diarrhoeal and six rotavirus diarrhoeal subjects. All individuals in the non
      diarrhoeal group responded well to PHA and had normal values for T-cell subsets.
      The number of positive responders to the rotavirus antigen increased gradually
      from 0% in the newborns to 92% in older children. The increasing risk of exposure
      to rotavirus infection is thought to be a chief cause of this age-related
      variation. All the rotavirus diarrhoeal patients responded well to the rotavirus
      antigen, indicating a potent test system. The T-cell responses to PHA and the T
      cell subsets were significantly low. This could be due to temporary T-cell
      suppression that may accompany viral infection. Our results are discussed in the
      context of previous studies.

PMID- 1376593
TI  - The prognosis of medical coma in Ibadan: results of multivariate analysis.
AB  - During a recent prospective investigation of 116 children with medical coma in
      Ibadan, 52 (45%) survived intact, 23 (20%) developed residual neurological
      deficits and the remaining 41 (35%) died. This series is concerned with the use
      of multivariate analysis in predicting outcome of medical coma in an individual
      patient, based mostly on clinical information (27 variables) obtained within 12
      hours of admission. Stepwise logistic regression analysis revealed that only 17
      of the 27 variables have independent significance in predicting outcome. When
      discriminant analysis was performed on these 17 variables so as to obtain a
      classification function of outcome (survived intact, survived with deficits and
      dead), 92% of the cases were correctly classified. Eight children were, however,
      seriously misclassified. These were four intact survivors and four dead cases who
      were classified as dead and survived without neurological sequelae, respectively.
      These results suggest that multivariate analysis of clinical and laboratory
      information obtained in the comatose state can provide predictive information.

PMID- 1376594
TI  - Subacute sclerosing panencephalitis in Riyadh, Saudi Arabia.
AB  - The clinical features and outcome of disease in 14 cases of subacute sclerosing
      panencephalitis (SSPE) diagnosed at the King Khalid University Hospital, Riyadh
      during an 8-year period are similar to those described elsewhere. Therapy was
      associated with arrest of deterioration for 2.5 years in one patient, and with
      survival after diagnosis for 2-7 years in four others. Many of the cases had
      initial misdiagnoses because of the frequently bizarre modes of presentation. It
      is thought that many more cases of SSPE occur in Saudi Arabia and also in many
      other tropical countries than are currently recognized. The establishment of
      national SSPE registries is advocated to improve early identification and
      management of cases.

PMID- 1376596
TI  - A study of core domains, and the core domain-domain interaction of cytochrome c
      fragment complex.
AB  - To gain insight into the folding mechanism of the cytochrome c complex, we
      prepared a complete set of homologous and hybrid two-fragment ferric complexes of
      four different types and related complexes from horse, tuna, yeast iso-l, and
      Candida cytochromes c. The complexes were characterized for structural
      properties. Apparent equilibrium constants of the complexes were determined to
      calculate delta G0 for binding. The results have allowed us to assign four core
      domains of the complex. A core domain is a structural region containing a
      hydrophobic core and the surrounding shell which folds and unfolds as a unit.
      Core domain 1 folds by itself and consists essentially of the right channel
      structure, found by R. E. Dickerson and colleagues, and a part of the heme. Core
      domains 2, 3, and 4, respectively, are assigned based on the cores located on the
      left (the Fe-S bond) and right sides and at the bottom of heme. Evidence of the
      core domain-domain interaction to stabilize the Fe-S bond, combined with the
      kinetic studies by G. R. Parr and H. Taniuchi, has led to a model of two
      alternative folding orders of the core domains for the horse type I complex:
      domain 1----3----2----4 or 1----2----3----4. Furthermore, delta G0 variation
      between the complexes has shown non-additive behavior, indicating the existence
      of a residue-residue interaction between the heme- and apofragments in the
      complex. Evidence suggests that this interaction in most cases occurs within or
      through the core groups of the ordered interface between the heme- and the apo
      fragments formed by folding of core domains 1, 2, and 3. Evidence also suggests
      that such core group interaction manifests itself in the interaction to stabilize
      the Fe-S bond and may be manifested in the core domain-domain interaction.

PMID- 1376595
TI  - Antiretroviral therapy: reverse transcriptase inhibition.

PMID- 1376597
TI  - The pyruvate dehydrogenase complex from the parasitic nematode Ascaris suum:
      novel subunit composition and domain structure of the dihydrolipoyl
      transacetylase component.
AB  - The pyruvate dehydrogenase complex (PDC) from muscle of the adult parasitic
      nematode Ascaris suum plays a unique role in its anaerobic mitochondrial
      metabolism. Resolution of the intact complex in high salt dissociates the
      pyruvate dehydrogenase subunit but leaves the dihydrolipoyl dehydrogenase subunit
      (E3) and two other proteins with apparent M(r)s of 45 and 43 kDa bound to the
      dihydrolipoyl transacetylase (E2) core. These proteins are not observable on
      Coomassie brilliant blue-stained gels of other eukaryotic PDCs, but the 45-kDa
      protein is similar in apparent M(r), pI, and sensitivity to trypsin to the Kb
      subunit of the bovine kidney PDH alpha kinase. Acetylation of the ascarid PDC
      with [2-14C]pyruvate under conditions designed to maximize the incorporation of
      label into protein yielded only a single radiolabeled subunit, E2. These results
      confirm earlier reports that the ascarid PDC lacks protein X, an integral
      component recently identified in other eukaryotic PDCs. About 1.6 to 1.8 mol of
      14C was incorporated/mole of E2, suggesting that the ascarid E2 contained two
      lipoly-bearing domains. Domain mapping of the 14C-acetylated ascarid E2 by
      limited tryptic digestion identified two lipoyl-bearing fragments with apparent
      M(r)s of 50 and 34 kDa and two core fragments with apparent M(r)s of 46 and 30
      kDa. The ascarid E2 domain structure appears to be similar to that of other E2s.
      However, it appears that the subunit-binding domain (E2B) of the ascarid E2 may
      be significantly larger or be flanked by larger than normal interdomain regions.
      An enlarged E2B domain may be necessary to accommodate the additional binding of
      E3 to the E2 subunit in the ascarid complex, in the absence of protein X.

PMID- 1376598
TI  - The differential diagnosis of primary peritoneal papillary tumors.
AB  - Primary tumors of the peritoneum are rare. Histological differentiation between
      papillary mesotheliomas, primary ovarian tumors, borderline tumors of the ovary
      with peritoneal deposits and primary peritoneal carcinoma may be difficult. The
      expression of vimentin, keratin, pankeratin, CEA, CA125, CA19-9, S100, B72.3 and
      BerEP4 was therefore investigated in twelve women with primary malignant
      peritoneal tumors, twelve women with pleural mesothelioma, eight women with
      serous ovarian carcinoma and four men with peritoneal mesothelioma. The marker
      pattern we used was no help in differentiating between metastatic ovarian
      carcinoma and primary peritoneal carcinomatosis. A combination of the markers
      S100, B72.3 and BerEP4 helped the distinction between mesotheliomas and the other
      malignancies. If two or all three markers are detectable, primary peritoneal
      carcinomatosis or metastatic ovarian carcinoma is the possible diagnosis. If none
      of the three markers are found, a diagnosis of mesothelioma is highly probable.

PMID- 1376599
TI  - Antigenic variation of the bovine ephemeral fever virus glycoprotein.
AB  - Glycoprotein-specific monoclonal antibodies (MAbs) were used to select escape
      mutants of bovine ephemeral fever (BEF) virus to determine the escape frequency
      for different epitopes and to construct an epitope map. At least six antigenic
      sites were detected by this method and escape frequencies between 10(-2) and 10(
      8) were recorded. One new non-conformational site was defined by a MAb, 5A5,
      which neutralized Berrimah and Kimberley viruses as well as three BEF virus
      strains. Batch to batch variation was detected in the BB7721 strain of BEF virus
      when tested for MAb neutralization. Eighteen strains of BEF virus, isolated from
      blood and insects from a variety of locations in Australia over a period of 33
      years, were examined using MAbs and at least one epitope could not be detected in
      strains isolated since 1975. Implications for vaccine development are discussed.

PMID- 1376600
TI  - [Refinement of the spatial structure of the gramicidin A ion channel].
AB  - The spatial structure of the gramicidin A (GA) transmembrane ion-channel was
      refined on the base of cross-peak volumes measured in NOESY spectra (mixing time
      tau m = 100 and 200 ms). The refinement methods included the comparison of
      experimental cross-peak volumes with those calculated for low-energy GA
      conformations, dynamic averaging of the low-energy conformation set and
      restrained energy minimization. Accuracy of the spatial structure determination
      was estimated by the penalty function Fr defined as a root mean square deviation
      of interproton distances corresponding to the calculated and experimental cross
      peak volumes. As the initial conformation we used the right-handed pi 6,3 LD pi
      6,3 LD helix established on the base of NMR data regardless of the cross-peak
      volumes. The conformation is in a good agreement with NOE cross-peak volumes (Fr
      0.2 to 0.5 A depending on NOESY spectrum). For a number of NOEs formed by the
      side chain protons, distances errors were found as much as 0.5-2.0 A. Restrained
      energy minimization procedure had little further success. However some of these
      errors were eliminated by the change in torsional angle chi 2 of D-Leu12 and
      dynamic averaging of the Val7 side chain conformations. Apparently, majority of
      deviations of the calculated and experimental cross-peak volumes are due to the
      intramolecular mobility of GA and cannot be eliminated within the framework of
      rigid globule model. In summary the spatial structure of GA ion-channel can be
      thought as a set of low-energy conformations, differing by the side chain torsion
      angles chi 1 Val7 and chi 2 D-Leu4 and D-Leu10 and the orientation of the C
      terminal ethanolamine group. Root mean square differences between the atomic
      coordinates of conformations are in the range of 0.3-0.8 A.

PMID- 1376601
TI  - The influence of signs prompting motorists to yield before marked crosswalks on
      motor vehicle-pedestrian conflicts at crosswalks with flashing amber.
AB  - The purpose of this experiment was to evaluate the effects of signs reading "STOP
      HERE FOR PEDESTRIANS" alone and in conjunction with advance stop lines on
      pedestrian safety at multilane crosswalks with pedestrian-activated amber
      flashing lights. Motorist and pedestrian behaviors measured throughout this
      experiment included the occurrence of various types of motor vehicle-pedestrian
      conflicts; the distance that motorists stopped before the crosswalk when yielding
      to pedestrians; and the percentage of motorists yielding to pedestrians. The
      introduction of the sign alone 50 feet (15.15 m) before the crosswalk increased
      the distance before the crosswalk that motorists yielded to pedestrians and
      reduced the percentage of motor vehicle-pedestrian conflicts whether the flashing
      light was activated or not. The addition of the advance stop line was associated
      with further improvements in both measures.

PMID- 1376602
TI  - Insulin-like growth factor I and erythropoiesis.
AB  - The bone marrow, the primary site of hematopoiesis, is a self-renewing system
      consisting of a unique micro-environment that promotes the differentiation and
      proliferation of the various hematopoietic cell lines. While many critical
      factors necessary for red cell production have been identified, the regulation of
      erythropoiesis has not been completely elucidated. In addition to multi-lineage
      growth factors (e.g. interleukin 3 or 4) and lineage-specific hematopoietic
      growth factors (e.g. erythropoietin), several lines of evidence suggest a key
      role for insulin-like growth factor I (IGF-I). First, growth hormone stimulates
      erythropoiesis and IGF-I is known to mediate many of growth hormone's actions
      (somatomedin hypothesis). Second, factors in bovine serum and in serum from an
      anephric human with erythropoietic activity distinct from erythropoietin have
      been identified as IGFs. Third, IGF receptors are found on both erythrocyte
      precursors as well as mature erythrocytes. Fourth, in vitro IGF-I stimulates
      erythropoiesis in bone marrow cultures. Fifth, IGF-I administration to neonatal
      or hypophysectomized animals results in increased erythropoiesis in vivo. Recent
      studies indicate that IGF-I at physiologic concentrations stimulates
      erythropoiesis and that growth hormone's action is indirect, occurring via IGF-I.
      The physiologic source of IGF-I for the bone marrow may be delivery from the
      serum (an endocrine mechanism) or synthesis within the bone marrow by stromal or
      other cells (a paracrine mechanism). Our recent studies have shown that mouse
      bone marrow stromal cells secrete both IGF-I and IGF binding proteins (IGFBPs).
      The role of IGFBPs in erythropoiesis is not known, but they might modulate the
      local concentration of IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376603
TI  - Variable gene usage, physiology and development of Ly-1+ (CD5+) B cells.
AB  - Two related features of Ly-1+ B cells (CD5+ B cells in man) are their biased
      specificities and variable gene usage, and their relationship to the bulk of Ly-1
      ('conventional') B cells. An emerging model views Ly-1+ B cells as a memory
      population in the adult animal, whose generation is largely limited to fetal and
      neonatal development. Selection based on germline-encoded self-reactivity then
      shapes the adult repertoire.

PMID- 1376604
TI  - Biochemical analysis of MHC and non-MHC lymphocyte membrane antigens.
AB  - Basic biochemical techniques have been skillfully used to characterize MHC-bound
      peptides and to examine the changes that occur in MHC molecules and lymphocyte
      membrane receptor complexes upon ligand binding. The fine tuning of these
      experimental approaches was possible because of the availability of a variety of
      biochemical and biological reagents.

PMID- 1376605
TI  - Polymerase chain reaction for detection of cytokine gene expression.
AB  - A powerful method to amplify reverse-transcribed RNA, the polymerase chain
      reaction can be used to measure cytokine gene transcription in a small number of
      cells, or in cases where there is low mRNA copy number. This technique may be
      used to obtain qualitative or quantitative determinations of cytokine gene
      expression. In this review we discuss the various strategies recently described
      for the evaluation of cytokine expression using the polymerase chain reaction.

PMID- 1376606
TI  - Organization of galanin-like immunoreactive neuronal systems in weakly electric
      fish (Apteronotus leptorhynchus).
AB  - Immunohistochemical procedures were used to investigate the distribution of
      galanin-like immunoreactive neuronal somata, fiber pathways and apparent
      termination fields in the gymnotiform brain. Immunoreactive somata were observed
      only in the hypothalamus and were confined to preoptic, lateral and caudal
      hypothalamic regions. Within these areas, positive cells tended to be most
      concentrated in juxtaventricular nuclei. Dense immunoreactive fiber systems
      originating from hypothalamic regions were seen to project in separate or
      coalescing fiber bundles to the basal telencephalan, thalamus/tuberal
      diencephalon, midbrain and brainstem. The density of positive axons and boutons
      was quite variable, but regions which displayed the most massive network of axons
      included structures within the hypothalamus itself (anterior periventricular
      preoptic nucleus, caudal and lateral hypothalamus), ventral telencephalon
      (superior and ventral subdivisions), thalamic/tuberal areas (central posterior
      nucleus and tuberal neuropil within the ventral territory of the prepacemaker
      nucleus) and brainstem nuclei (dorsal reticular nucleus and the medial
      paralemniscal nucleus). Within these areas axons appeared more randomly
      distributed and varicose than along fiber tracs, and in counterstained sections
      were occasionally seen in apposition to unstained neuronal cell bodies and
      dendrites. In addition, a system of fibers was seen in the neurointermediate lobe
      of the pituitary. It is concluded that galanin-like immunoreactive neurons in the
      gymnotiform brain have a more restricted distribution than those in mammals, and
      that the major fiber systems emanating from the hypothalamus resemble the diverse
      projections of the tuberomammillary nucleus of higher vertebrates. The anatomy of
      galanin-like immunoreactive systems in the apteronotid brain suggests a role in
      neuroendocrine regulation and an involvement with anatomical areas controlling
      aggressive and courtship behaviour.

PMID- 1376607
TI  - Afferent connections of the rat substantia nigra pars lateralis with special
      reference to peptide-containing neurons of the amygdalo-nigral pathway.
AB  - The afferent connections of the rat substantia nigra pars lateralis have been
      studied using the retrograde axonal transport of fluorescent latex microspheres.
      The most numerous groups of retrogradely labelled nerve cell bodies were observed
      bilaterally in the parabrachial complex and several hypothalamic nuclei, whereas
      the parietal neocortex, the fundus striati, the central nucleus of the amygdala
      and the bed nucleus of the stria terminalis were labelled on the injected side
      only. The neuronal projections from the central amygdaloid nucleus to the
      substantia nigra pars lateralis and lateral part of the rostral pars compacta
      have additionally been confirmed by anterograde tracing using wheat-germ
      agglutinin coupled to horseradish peroxidase. The presence of some peptides in
      this pathway was studied by combining the use of the same retrograde tracer with
      immunofluorescence after intra-amygdaloid injections of colchicine. With this
      method, we have demonstrated that Met-enkephalin, dynorphin and neurotensin are
      probably utilized as neurotransmitters or co-transmitters in the neurons of the
      amygdalo-nigral pathway.

PMID- 1376608
TI  - Carnosine, nerve growth factor receptor and tyrosine hydroxylase expression
      during the ontogeny of the rat olfactory system.
AB  - The localizations of carnosine, nerve growth factor (NGF) receptor and tyrosine
      hydroxylase (TH) were studied in the embryonic and postnatal rat olfactory bulb
      and epithelium by means of single- and double-immunostaining methods. Tyrosine
      hydroxylase ontogeny was also evaluated at the mRNA level by in situ
      hybridization. All these molecules were expressed in the olfactory bulb but with
      different developmental patterns and cellular localization: carnosine
      immunoreactivity is seen from embryonic day 17 in primary olfactory neurons
      scattered in the nasal cavity and in fibres projecting from them to the olfactory
      bulb. Nerve growth factor-receptor immunoreactivity associated with small glial
      like cells is visible in some glomeruli starting from the second day of postnatal
      life. At postnatal day 10 NGF-receptor immunoreactivity is extended to all
      glomeruli. Periglomerular neurons expressing TH mRNA and protein are present
      prenatally and their number sharply increases during the early postnatal
      development. Double-staining methods show that TH and NGF-receptor
      immunoreactivity do not overlap in cell bodies and processes. In addition, NGF
      receptor immunoreactivity is not colocalized with carnosine. These findings
      definitely exclude NGF-receptor expression in periglomerular and primary
      olfactory neurons, suggesting that at least part of NGF-receptor expression in
      the olfactory bulb is associated with glial cells. In addition, they provide the
      first immunohistochemical data on carnosine ontogeny and confirm at the mRNA
      level previous studies on the ontogeny of TH protein.

PMID- 1376609
TI  - Multienzyme membranes for biosensors.
AB  - Artificial multienzyme complexes were prepared in which enzymes were covalently
      bound to polysaccharide structures activated with urea and formaldehyde. Double
      enzyme complexes of glucose oxidase and catalase, a glucose oxidase and
      invertase, were prepared by immobilization on to cellulose fabric. Also, catalase
      was covalently bound to soluble dextran. The resulting multienzyme systems were
      highly active and stable, making them suitable for use in measuring the
      concentrations of glucose and saccharose in solutions. The measurements were
      performed using an amperometric oxygen electrode and multienzyme membranes
      containing glucose oxidase and catalase for the first substrate, as well as
      glucose oxidase bound to cheese-cloth and a 'liquid' membrane of dextran-bound
      catalase. To determine the concentration of saccharose, a multienzyme membrane
      with bound glucose oxidase and invertase was used in combination with a 'liquid'
      dextran-catalase. The enzyme electrodes exhibited a measuring range of 0.1-5 mol
      dm-3 and a response time of 2-3 min. The electrodes may be used for measuring
      saccharose and glucose concentrations both in fermentation broths and food
      products.

PMID- 1376610
TI  - Palliative care: with one voice.

PMID- 1376611
TI  - Palliative care: a Yorkshire approach.
AB  - Palliative care services have traditionally tended to concentrate on the needs of
      patients with cancer. The philosophy of Yorkshire Health is to extend those
      services to all people with life-threatening diseases. The progress in service
      provision which has taken place in the region is described, but work still needs
      to be done in training professionals to provide the appropriate level of skilled
      care to patients in hospitals, hospices and community.

PMID- 1376612
TI  - Localization of endoderm-specific mRNAs in differentiating F9 embryoid bodies.
AB  - Primitive endoderm in the peri-implantation mouse embryo differentiates into two
      separate lineages, visceral and parietal endoderm (VE and PE). F9 teratocarcinoma
      cells, when grown in suspension in the presence of retinoic acid (RA),
      differentiate into embryoid bodies (EBs) which can be used as a model system to
      study the spatially appropriate induction of VE- and PE-specific gene expression.
      We have used a whole mount in situ hybridization technique to follow the
      localization of VE-specific AFP and PE-specific tPA mRNAs during EB
      differentiation. We show that the putative endoderm-specific markers are
      localized to the endoderm in mature EBs, and that AFP mRNA is localized to the
      apical edge of the VE in RA EBs. Surprisingly, prior to localization of endoderm
      specific markers at the periphery of EBs, these genes are expressed at low to
      moderate levels in all cells of the EB. Our data suggest that the establishment
      of endoderm in EBs is position dependent and not the result of sorting out of
      predetermined, randomly distributed cells. Our observations also suggest a two
      step process for establishing endoderm-specific gene expression, involving up
      regulation of transcripts throughout the EB prior to the restriction of their
      expression to the outer differentiating cell layer.

PMID- 1376613
TI  - Testicular and adrenocortical function in healthy men and in men with benign
      prostatic hyperplasia.
AB  - The influence of aging upon serum concentrations of testicular steroids, sex
      hormone binding globulin (SHBG) and pituitary hormones and on adrenal steroid
      levels and adrenal steroid response to ACTH was studied in 81 healthy men aged 20
      87 years. These endocrine variables were also compared in 43 patients with benign
      prostatic hyperplasia (BPH), aged 58-89 years and in a subgroup of 41 men, aged
      58-87 years, from the above mentioned reference population. The normal endocrine
      aging was characterized by a rise in SHBG levels, decreasing levels of testicular
      steroids and non-SHBG-bound testosterone (NST) and increasing gonadotropin levels
      and decreasing concentrations of total estrone. Adrenal androgen levels decreased
      in the presence of unchanged levels of cortisol and the adrenal steroid response
      to ACTH changed by decreasing increments in dehydroepiandrosterone (DHA) and
      increasing increments in 17 alpha-hydroxyprogesterone (17OHP). With the exception
      of the alterations in SHBG and adrenal androgens, all these changes were finished
      before the seventh decade of life. BPH patients had elevated levels of
      testosterone and NST in the presence of normal SHBG and gonadotropin levels,
      elevated levels of DHA and DHA sulfate (DHAS) in the presence of normal cortisol
      levels, a "younger" pattern of adrenal steroid response to ACTH as judged from
      the increments in DHA and 17OHP, elevated ratios between estrone and 4-androstene
      3,17-dione suggesting an increased peripheral aromatization and subnormal
      prolactin levels. BPH patients may be considered as "endocrinologically younger"
      than healthy subjects. DHA and especially its proximate metabolite 5-androstene-3
      beta, 17 beta-diol exert powerful estrogenic effects on the receptor level. Thus
      the elevated levels of DHA and DHAS in the BPH patients may create an
      hyperestrogenic condition in addition to the slight hyperandrogenicity caused by
      the elevated NST levels. Both endocrine aberrations may play a role in the
      etiology of BPH, in accordance with the dual sex steroid sensitivity of the
      periurethral glands.

PMID- 1376614
TI  - Regulation of progesterone secretion in human syncytiotrophoblast in culture by
      human chorionic gonadotropin.
AB  - In the present investigation we sought to define the specific sites in the
      pathway of placental progesterone biosynthesis that underlie the action of human
      chorionic gonadotropin (hCG). When the cells were challenged with dibutryl cAMP
      (dbcAMP), forskolin or isobutylmethylxanthine, they produced significantly higher
      amounts of progesterone which in the presence of the hCG antibody was reduced to
      the level of the control set of cells. Trophoblast cells cultured in serum free
      medium with 25-hydroxycholesterol (25-OHC) produced increased amounts of
      progesterone. In the presence of hCG antibody at a concentration which
      neutralized the secreted hCG, the steroid production was completely blocked, even
      when the 25-OHC was added to the medium. Also, direct quantitation of the
      cytochrome P450 SCC enzyme in the absence of hCG indicated a significant
      decrease. The exogenous addition of low density lipoproteins (LDL) increased the
      progesterone secretion by the trophoblast cells in culture. Neutralization of hCG
      by the antibodies, however, drastically reduced the LDL induced progesterone
      secretion, which was restored by the addition of dbcAMP to the medium. Based on
      these findings, we suggest a stimulatory effect of hCG on normal trophoblast
      cells at the level of LDL utilization and cytochrome P450 SCC enzyme. Since
      dbcAMP could mimic these actions of hCG, the data suggest a possible
      autocrine/paracrine role of hCG on the trophoblast cells. An additive effect of
      hCG and cAMP on progesterone secretion observed in our studies, indicate that
      apart from hCG, adenylate cyclase activity may also be regulated by other
      factors.

PMID- 1376615
TI  - Quantitative virological measures of antiretroviral therapy.

PMID- 1376616
TI  - Sanctuary site relapse in chemotherapy-treated testicular cancer.
AB  - The testis and central nervous system (CNS) may act as sanctuary sites for
      testicular germ cell tumours, as cytotoxic drugs penetrate these areas less well
      than systemic sites. We describe three patients who relapsed in the testis (one
      patient) or CNS (two patients) after receiving chemotherapy for responsive
      systemic disease. All three were asymptomatic at relapse, which was first
      manifest by rising tumour marker levels. These sanctuary site relapses were
      managed locally with surgery +/- radiotherapy. Two patients were rendered disease
      free; one died of progression of his local disease only. Sanctuary site tumour
      should be considered when relapse occurs in the setting of otherwise
      chemosensitive disease; local therapy may be curative.

PMID- 1376617
TI  - A preoperative single course of high-dose cisplatin and bleomycin with
      glutathione protection in bulky stage IB/II carcinoma of the cervix.
AB  - One course of preoperative chemotherapy including high-dose cisplatin (40 mg/m2
      daily for 5 consecutive days) with glutathione protection and bleomycin (15 mg on
      days 2, 8 and 9) was administered to 27 patients with bulky operable cervical
      carcinoma (stage IB/II) in a pilot study. In all patients the tumor diameter was
      greater than 4 cm. Surgery (radical hysterectomy with pelvic and para-aortic
      lymphadenectomy) was planned within one month of chemotherapy. In 27 evaluable
      patients, nausea/vomiting was the most pronounced side effect. Significant (but
      transient) increases in serum transaminases were detected in 19 patients.
      Electrolyte imbalance (hypokalemia) was detected in 6 patients (one with
      hypocalcemia). These reversible effects were not associated with other signs of
      renal toxicity. Objective clinical responses were observed in 21 patients, 18 of
      them partial and 3 complete responders (pathologically confirmed in 2). Radical
      hysterectomy with pelvic and para-aortic lymphadenectomy was performed with no
      particular complications. The shrinking of bulky tumor made the operation easier,
      especially in parametrial resections. High-dose cisplatin chemotherapy prior to
      surgery is feasible with acceptable toxicity. The encouraging results of this
      study warrant further investigations to define the role of neoadjuvant therapy.

PMID- 1376618
TI  - Treatment of high-risk, nonseminomatous testicular cancer with cisplatin,
      ifosfamide and bleomycin: long-term results.
AB  - Thirty-four patients with stage IIC (unresectable, retroperitoneal tumor mass
      (RTM) greater than 5 cm), stage IVC (minimal lung metastases less than 10 cm3 and
      RTM greater than 5 cm) and IVD (lung metastases greater than 10 cm3 and RTM
      greater than 5 cm), who had not received previous chemotherapy, were treated with
      cisplatin (40 mg/m2, on days 2-4), ifosfamide (5 g/m2, on days 1 and 5) and
      bleomycin (30 mg, on days 1, 8, 15) (PIB), every 21 days. Twenty of the 34
      patients (59%) achieved a complete remission (CR). Furthermore, five patients
      (15%) showed no evidence of disease (NED) after surgical removal of residual
      tumor masses (NED rate of 74%). A tumor marker-negative partial remission (PR)
      occurred in 3/34 patients (9%), and a tumor marker-positive PR in another 3/34
      patients (9%). Three patients did not respond to this regimen. At a median follow
      up period of 38 months (range, 15-47 months), 26/34 patients (76%) were alive, 21
      (62%) of them without evidence of disease and three with a stable tumor marker
      negative remission. Major toxicity consisted of myelosuppression, neurotoxicity
      and nephrotoxicity. Chemotherapy-related mortality occurred in two patients (one
      septicemia and one bleomycin-induced lung fibrosis). In conclusion, PIB is an
      effective induction regimen in patients with high-risk NSTC. However, controlled
      clinical trials are necessary to prove the superiority of dose intensification
      schedules.

PMID- 1376619
TI  - Single agent activity of carboplatin in patients with previously untreated non
      seminomatous germ cell tumours.
AB  - The response to a single course of carboplatin has been investigated in 12
      patients with previously untreated non-seminomatous testicular germ cell tumours.
      Patients received one course of carboplatin at a dose calculated to achieve a
      target area under the free carboplatin plasma concentration versus time curve
      (AUC) of 7 mg/ml x mins using the formula: dose (mgs) = target AUC x (GFR + 25).
      Response to carboplatin was assessed after a single course and treatment was then
      continued on the POMB/ACE schedule. Ten of 12 patients had either a greater than
      50% decrease in serum HCG and/or AFP levels or a greater than 50% decrease in
      tumour volume after a single course of carboplatin. No patient had evidence of
      disease progression after carboplatin. This study demonstrates that single agent
      carboplatin is highly active in patients with non-seminomatous testicular germ
      cell tumours and thus provides evidence to justify its inclusion in chemotherapy
      combinations.

PMID- 1376620
TI  - Increased thermal stability of proteins in the presence of naturally occurring
      osmolytes.
AB  - Organisms and cellular systems which have adapted to stresses such as high
      temperature, desiccation, and urea-concentrating environments have responded by
      concentrating particular organic solutes known as osmolytes. These osmolytes are
      believed to confer protection to enzyme and other macromolecular systems against
      such denaturing stresses. Differential scanning calorimetric (DSC) experiments
      were performed on ribonuclease A and hen egg white lysozyme in the presence of
      varying concentrations of the osmolytes glycine, sarcosine, N,N-dimethylglycine,
      and betaine. Solutions containing up to several molar concentrations of these
      solutes were found to result in considerable increases in the thermal unfolding
      transition temperature (Tm) for these proteins. DSC scans of ribonuclease A in
      the presence of up to 8.2 M sarcosine resulted in reversible two-state unfolding
      transitions with Tm increases of up to 22 degrees C and unfolding enthalpy
      changes which were independent of Tm. On the basis of the thermodynamic
      parameters observed, 8.2 M sarcosine results in a stabilization free energy
      increase of 7.2 kcal/mol for ribonuclease A at 65 degrees C. This translates into
      more than a 45,000-fold increase in stability of the native form of ribonuclease
      A over that in the absence of sarcosine at this temperature. Catalytic activity
      measurements in the presence of 4 M sarcosine give kcat and Km values that are
      largely unchanged from those in the absence of sarcosine. DSC of lysozyme
      unfolding in the presence of these osmolytes also results in Tm increases of up
      to 23 degrees C; however, significant irreversibly occurs with this
      protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376621
TI  - Gramicidin channels that have no tryptophan residues.
AB  - In order to understand how aromatic residues modulate the function of membrane
      spanning proteins, we examined the role of the four tryptophans in gramicidin A
      (gA) in determining the average duration and permeability characteristics of
      membrane-spanning gramicidin channels; the tryptophan residues were replaced by
      tyrosine (gramicidin T, gT), tyrosine O-benzyl ether [gramicidin T(Bzl),
      gT(Bzl)], naphthylalanine (gramicidin N, gN), and phenylalanine (gramicidin M
      enantiomer, gM-). These analogues form channels with durations and conductances
      that differ some 10- and 16-fold, respectively. The single-channel conductance
      was invariably decreased by the Trp----Yyy replacement, and the relative
      conductance alterations were similar in phosphatidylcholine (DPhPC) and
      monoglyceride (GMO) bilayers. The duration variations exhibited a more complex
      pattern, which was quite different in the two membrane environments: in DPhPC
      bilayers, gN channels have an average duration that is approximately 2-fold
      longer than that of gA channels; in GMO bilayers, the average duration of gN
      channels is about one-tenth that of gA channels. The sequence-dependent
      alterations in channel function do not result from alterations in the channels'
      peptide backbone structure, because heterodimers can form between the different
      analogues and gramicidine A, and there is no energetic cost associated with
      heterodimer formation [cf. Durkin, J. T., Koeppe, R. E., II, & Andersen, O. S.
      (1990) J. Mol. Biol. 211, 221]. The alterations in permeability properties are
      consistent with the notion that Trp residues alter the energy profile for ion
      permeation through long-range electrostatic interactions.

PMID- 1376622
TI  - Moderate oxidation of hypertriglyceridemic low-density lipoprotein causes
      apolipoprotein B epitope change and enhances its uptake by macrophages.
AB  - We prepared monoclonal antibody (MabB4) that selectively binds to acetylated low
      density lipoprotein (LDL). Native hypertriglyceridemic LDL (HT-LDL) obtained from
      IIb and native normotriglyceridemic LDL (NT-LDL) from type IIa scarcely bound
      with MabB4. When these LDL were oxidized moderately by incubation with copper
      ions, the binding of MabB4 to HT-LDL was enhanced compared to that of NT-LDL,
      although the contents of the hydroperoxide they produced were the same. The
      incorporation of moderately oxidized HT-LDL into macrophages was enhanced
      compared to that of NT-LDL, and the rate of incorporation parallel the binding of
      LDL for MabB4. These results suggested that moderate oxidation of HT-LDL
      expressed some apolipoprotein B epitope on the surface of acetylated LDL to a
      much greater degree than NT-LDL, and that this expressed epitope might work as a
      ligand of moderately oxidized HT-LDL for the recognition by macrophages.

PMID- 1376623
TI  - Proliferative responses of a bovine leukemia virus-infected lymphoblastoid B-cell
      line by its culture supernatant and cytokines.
AB  - The growth-promoting activity in the culture supernatant of bovine lymphoblastoid
      B-cell lines (BL2M3 and BL312) were examined. BL2M3 cells proliferated well in
      response to conditioned medium (CM) obtained from BL2M3 and BL312 cell cultures.
      These BL2M3 and BL312 CM were used as sources of BL2M3 cell growth-promoting
      factor (BL2M3-GPF). BL2M3-GPF was sensitive to acid (pH 2) and alkali (pH 10) and
      was heat-labile. Proliferative responses of BL2M3 cells were not induced by human
      recombinant (r)IL 1, rIL 2, rIL 6, granulocyte-colony stimulating factor (rG-CSF)
      or tumor necrosis factor (rTNF)-alpha. Human low molecular weight B cell-growth
      factor (LMW-BCGF) was, however, capable of augmenting the proliferation of BL2M3
      cells. BL2M3 cells formed clusters in response to LMW-BCGF, whereas they showed
      single and discete appearance in the presence of BL2M3-GPF. These results
      suggested that bovine lymphoblastoid B-cell lines might release and respond to
      the growth-promoting factor for in vitro proliferation of its own cell line,
      BL2M3.

PMID- 1376624
TI  - Changes in intracellular and cell surface localization of Le(x) epitope during
      germ cell differentiation in fetal mice.
AB  - Changes in the intracellular and cell surface localization of Lewis x (Le(x))
      determinants in germ cells during fetal development in mice were examined by
      light and electron microscopy. Light microscopically, in undifferentiated gonads
      on day 12 post coitum (p.c.), the anti-Le(x) monoclonal antibody (MAb) was
      specifically bound to the plasma membranes and to the cytoplasmic granule-like
      structures of germ cells. In the testes on day 13 p.c., most of the germ cells
      were enclosed within the testicular cords and showed an MAb-positive reaction
      which was restricted mainly to the cytoplasmic granule-like structures. The
      reaction on the plasma membranes almost disappeared. On the other hand, the
      ectopic germ cells still showed a positive reaction on their plasma membranes. In
      the ovaries on day 13 p.c., the germ cells also exhibited positive reactions both
      on the plasma membranes and on the granule-like structures. Immunoelectron
      microscopic observations agreed well with these light microscopic observations in
      such a way that both the plasma membranes and the "small dense bodies" (SDB) were
      positive in undifferentiated gonads on day 12 p.c. In the germ cells organized
      into the testicular cords, the reaction to anti-Le(x) MAb became restricted to
      the SDB. These results may indicate that such intracellular changes in Le(x)
      determinants during germ cell differentiation are associated with the enclosure
      of germ cells within the testicular cords.

PMID- 1376625
TI  - Molecular cloning and immunological analysis of immunodominant piroplasm surface
      proteins of Theileria sergenti and T. buffeli.
AB  - cDNA libraries of Theileria sergenti and T. buffeli piroplasms were constructed
      in lambda gt11 and screened with rabbit anti-piroplasm sera. A major antigen of
      T. sergenti (33 kDa) and that of T. buffeli (34 kDa) was identified from the
      recombinant phages by using recombinant antigen-selected monospecific antibodies.
      The reactivities of the cloned proteins with rabbit antisera, infected calf sera
      and mouse monoclonal antibody suggested that the 33 and 34 kDa proteins expressed
      species-common and species-specific epitopes. The DNA probes from these
      recombinant clones showed species-specific hybridizations in Southern blotting
      with genomic DNA from piroplasms. These results indicate that the Japanese T.
      sergenti can be distinguishable from the Australian T. buffeli with regard to a
      polymorphism of the major immunodominant proteins of piroplasm.

PMID- 1376626
TI  - Serological heterogeneity of Actinobacillus (Haemophilus) pleuropneumoniae
      serotype 5 strains.

PMID- 1376627
TI  - Plasminogen activators in the human endometrium, cellular origin and hormonal
      regulation.
AB  - Endometrial tissue explants in culture were found to release urokinase-type
      plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). In
      order to identify their cellular origin and possible hormonal regulation,
      enriched cultures of glandular epithelial cells and stromal cells were prepared
      from fresh endometrium, and the cultures treated with hormones. Both epithelial
      and stromal cell cultures were found to secrete u-PA and t-PA. Treatment of
      epithelial cell cultures with oestradiol, progesterone and DH-testosterone had no
      effect on the secretion of t-PA or u-PA. In stromal cell cultures, on the other
      hand, the secretion of u-PA was significantly reduced after treatment with
      progesterone, whereas oestradiol and DH-testosterone had no effect. This
      reduction of u-PA antigen in the tissue culture medium did not result from a
      reduction of the relative level of u-PA mRNA in the cells, suggesting that the
      synthesis of u-PA was not reduced. Alternatively, an increased clearance of u-PA
      by the cells from the medium may explain the reduction. This in vitro observation
      probably reflects the in vivo reduction of u-PA in endometrial secretion during
      the secretory phase.

PMID- 1376628
TI  - The interferons and their use in condyloma acuminata.
AB  - There are three naturally occurring interferons: alfa, beta, and gamma. Alfa,
      derived from lymphoblastic tissue, is approved by the Food and Drug
      Administration for the treatment of condyloma acuminata (genital or venereal
      warts). Genital warts are caused by human papillomaviruses, of which more than 50
      subtypes have been described. Traditional therapies have centered on destruction
      of the lesions by either cytotoxic or physical modalities. Intralesional
      interferon exerts its antiviral effects on infected cells without causing damage
      to the surrounding tissue. In general, success rates with intralesional
      interferon alfa are comparable to traditional modalities. There is also evidence
      that interferon alfa might be particularly useful in the treatment of lesions
      that have failed to respond to other modalities.

PMID- 1376629
TI  - Meniscus-like synovial fold in the atlantoaxial (C1-C2) joint.
AB  - Some of the synovial joints in the human body have a fibrocartilaginous disc
      interposed between the joint surfaces to absorb or evenly distribute loads.
      Examples of fibrocartilagenous discs include the intervertebral disc, knee joint
      meniscus, and triangular fibrocartilages in the distal radioulnar joint and the
      acromioclavicular joints. The joint capsule and the surrounding tissue from nine
      cervical spines (18 C1-C2 joints) were dissected and prepared for gross
      examination and histology. We found meniscus-like synovial folds in 13 of the 18
      atlantoaxial joints. These folds were located at the anteromedial and
      posteromedial aspect of the joint. Each synovial fold was of semilunar shape,
      with a thickened outer edge and thin inner edge giving a wedge-shape cross
      section. In one case, the synovial fold was grossly similar in appearance to a
      knee joint meniscus, and on histological examination there was evidence of
      cartilagenous metaplasia in part of the fold. The findings are compared with the
      limited data reported in the literature.

PMID- 1376630
TI  - Clinical value of measuring the interferon-induced enzyme 2'-5'-oligoadenylate
      synthetase in children.
AB  - 2'-5'-oligoadenylate synthetase, an interferon-induced enzyme and a sensitive
      indicator of the presence of interferon, was measured in peripheral blood
      mononuclear cells in children with inflammatory disorders of known and unknown
      origin in order to assess the value of such a test in patient management.
      Differences in median 2'-5'-oligoadenylate synthetase values in groups of
      children with viral or bacterial diseases or healthy children were observed.
      Considerable overlap of the 2'-5'-oligoadenylate synthetase range in the three
      groups was observed. All children with acute viral infections had increased
      levels early in their disease and a low value clearly argued against an acute
      viral infection. However, as more than one-third of children with bacterial
      diseases displayed elevated 2'-5'-oligoadenylate synthetase concentrations,
      distinction between a viral and bacterial cause of disease by measuring this
      enzyme was difficult. Estimation of 2'-5'-oligoadenylate synthetase
      concentrations in patients with inflammatory diseases of unknown origin,
      including juvenile rheumatoid arthritis, systemic lupus erythematosus, idiopathic
      uveitis and glomerulonephritis did not contribute to establishing a diagnosis or
      measuring disease activity.

PMID- 1376631
TI  - [Esophageal cancer: which palliation is the best?].

PMID- 1376632
TI  - [Endoscopic therapy of bronchial stenoses].

PMID- 1376634
TI  - Microglia isolated from rat brain secrete a urokinase-type plasminogen activator.
AB  - In a previous study, we found particular proteases which degrade myelin basic
      protein (MBP) in a conditioned medium of cultured rat brain microglia. The MBP
      degrading activity in microglial-conditioned medium (Mic-CM) increased markedly
      in the presence of plasminogen. By Sephadex G-150 column chromatography,
      plasminogen-dependent MBP degrading activity was eluted at the position of about
      47 kDa and 28 kDa. Furthermore slight plasminogen-dependent protease activity in
      the presence of fibrin (tissue plasminogen activator activity) was detected at a
      molecular weight of about 68 kDa. The two molecular forms (47 kDa and 28 kDa) of
      plasminogen-dependent protease were demonstrated by casein-zymography, and it was
      suggested that they were urokinase type-plasminogen activators (uPA). This
      suggestion was confirmed by immunoblotting using anti-uPA antiserum. The unique
      28 kDa type was considered to be produced from the 47 kDa form by limited
      proteolysis. Secretion of PA from microglia was demonstrated by cell zymography.
      In contrast, significant secretion of plasminogen activator inhibitor could not
      be detected in the Mic-CM. In addition, lipopolysaccharide significantly
      decreased the secretion of PA from microglia, while interleukin-1 and basic
      fibroblast growth factor enhanced the secretion.

PMID- 1376633
TI  - Further studies on platelet-mediated neurotoxicity.
AB  - The mechanism of ischemic neuronal injury is not fully resolved. The present view
      is that vascular occlusion per se does not fully account for the extent of
      neurological dysfunction. We hypothesized that platelet secretory products might
      contribute to ischemic neuronal injury in the central nervous system (CNS)
      (Joseph et al., Stroke, 20 (1989) 38-44 and 1316-1319). Our preliminary studies
      using organotypic rat spinal cord cultures exposed to human platelet and its
      secretory products, revealed that platelet product(s) had neurotoxicity. Further
      studies, using the same methods, were conducted here, with the addition of
      several refinements such as use of gel-filtered platelets (as opposed to washed
      platelets), adding additional relevant controls including platelet membranes, red
      blood cells and washed rat platelets. The results confirmed our initial finding
      that an agent(s) in platelet secretion is neurotoxic. Subsequently, we identified
      serotonin (5HT), a major platelet product, as having toxic effects on neurons.
      This toxicity of 5HT appeared to be blocked by ketanserin, a 5HT2 receptor
      antagonist. Judging by the concentrations of 5HT that demonstrated neurotoxicity
      in these in vitro studies, it appears that products secreted from activated
      platelets could have pathological significance in vivo.

PMID- 1376635
TI  - A 35 kDa Fos-related antigen is co-localized with substance P and dynorphin in
      striatal neurons.
AB  - The rat striatum after dopamine denervation followed by repeated apomorphine
      treatment was examined for the co-expression of c-fos and Fos-related antigens
      with dynorphin, substance P and [Met5]enkephalin using Western blot and
      immunohistochemical techniques. Administration of apomorphine, a dopamine
      agonist, elevated the level of 35 kDa Fos-related antigen which co-localized with
      dynorphin and substance P, but not enkephalin, in striatal neurons.

PMID- 1376637
TI  - Of mice and men: genetic skin diseases of keratin.

PMID- 1376636
TI  - Ultrastructural localization of nitric oxide synthase immunoreactivity in guinea
      pig enteric neurons.
AB  - Electron microscopic immunocytochemistry was used to localize immunoreactivity
      for nitric oxide synthase (NOS) in whole-mount preparations of myenteric plexus
      and circular muscle from guinea-pig ileum. NOS immunoreactivity was patchily
      distributed in myenteric neurons and was not specifically associated with any
      subcellular organelle or with the plasma membrane. This localization leaves
      unanswered the question of how nitric oxide is stored and released. NOS
      immunoreactive fibres in the circular muscle were found closer than 100 nm to
      muscle cells. NOS immunoreactive nerve fibres made synaptic contacts with NOS
      immunoreactive and non-immunoreactive enteric neurons. These results indicate
      that nitric oxide may regulate the activity of both myenteric neurons and smooth
      muscle.

PMID- 1376638
TI  - An endothelial ligand for L-selectin is a novel mucin-like molecule.
AB  - The adhesive interaction between circulating lymphocytes and the high endothelial
      venules (HEV) of lymph nodes (LN) is mediated by lymphocyte L-selectin, a member
      of the selectin family of cell adhesion proteins. Previous work has identified a
      sulfated 50 kd glycoprotein (Sgp50) as an HEV ligand for L-selectin. We now
      report the purification of this glycoprotein and the utilization of the derived N
      terminal amino acid sequence to clone a cDNA. The predicted sequence reveals a
      novel, mucin-like molecule containing two serine/threonine-rich domains. The mRNA
      encoding this glycoprotein is preferentially expressed in LN. Antibodies against
      predicted peptides immunoprecipitate Sgp50 and stain the apical surface of LN
      HEV. These results thus define a tissue-specific mucin-like endothelial
      glycoprotein that appears to function as a scaffold that presents carbohydrates
      to the L-selectin lectin domain.

PMID- 1376639
TI  - An antigenic determinant on human centromere protein B (CENP-B) available for
      production of human-specific anticentromere antibodies in mouse.
AB  - Centromere protein B (CENP-B) is one of the centromere DNA binding proteins
      constituting centromere heterochromatin throughout the cell cycles. Some
      components of mammalian centromeres including CENP-B are target antigens for
      autoimmune disease patients, often those with scleroderma. Recent isolations of
      CENP-B genes from human and mouse suggested that CENP-B was highly conserved
      among mammals. From the previous analysis of the reactivity of patient
      anticentromere sera, two autoepitopes have been located on the DNA binding domain
      at the amino-terminal region. The amino acid sequences for both the epitopes are
      perfectly conserved in the two species, human and mouse. In this study, to
      identify a human-specific antigenic determinant, the remaining two epitopes were
      further located in separate carboxyl-terminal regions of human CENP-B. Although
      the amino acid sequence of one epitope is identical to that of the corresponding
      region in mouse CENP-B, the other has a less homologous sequence. To confirm that
      the latter epitope was available for production of human-specific anticentromere
      antibodies, mice were immunized with the recombinant human CENP-B product. One
      serum that exclusively stained human centromere structure, but not that of other
      mammals, was identified in the immunofluorescence microscopic observation. The
      epitope analysis showed that the less conserved one was recognized by this serum.
      These results suggested that the corresponding region defines the antigenic
      determinants for the species specificity.

PMID- 1376640
TI  - Isolation and characterization of nuclei from rice embryos.
AB  - A method has been developed to isolate pure preparations of nuclei in high yield
      from commercially available viable rice embryos (germ), employing extraction with
      buffer solution containing glycerol (without detergent) and polyamine, followed
      by centrifugation on a 30% Percoll cushion. The intactness of the isolated nuclei
      was confirmed by light microscopy as well as electron microscopy. The protein
      profiles of both whole nuclei and nuclear extracts obtained by SDS-PAGE,
      organellar marker enzyme activities, DNA and RNA analyses, and in vitro RNA
      synthesis, all indicate that the highly purified nuclei are isolated from rice
      embryos.

PMID- 1376641
TI  - Inhibitory effects of bis(2-aminohexyl)disulfide and its analogues on
      polymorphonuclear leukocyte functions in vitro.
AB  - Water soluble analogues of the anti-inflammatory compound, bis(2
      aminopropyl)disulfide dihydrochloride (compd. I) with a butyl (II), phenyl (III),
      benzyl (IV) or pyrrolidinyl group (V) instead of the methyl group were
      synthesized, and their effects on the functions of cells related to inflammation
      were studied in vitro. Compounds II, III and IV showed much higher inhibitory
      activity than compd. I on formyl Met-Leu-Phe (FMLP)-induced O2(-)-generation of
      polymorphonuclear leukocytes (PMNs) and platelet aggregation. Compound II showed
      the strongest activity among the compounds (IC50 values: 2.6 microM). The
      inhibition of O2(-)-generation of PMNs by compd. II was the most effective when
      FMLP was used as a stimulant rather than when phorbol myristate acetate, A-23187
      and opsonized zymosan were used. However, compd. II was not an O2(-)-scavenger.
      Compounds II, III and IV significantly inhibited a series of activation processes
      in PMNs, chemotaxis, phagocytosis and lysosomal enzyme release at doses ranging
      from 10 to 100 microM. Under these doses, compds II, III and IV did not affect
      the histamine release from mast cells or the hemolysis of erythrocytes. These
      results strongly suggest that the anti-inflammatory action caused by compd. II
      and its analogues was at least partly due to inhibition of several functions of
      PMNs and platelets.

PMID- 1376642
TI  - Characterization of a mouse hepatocyte growth-stimulating factor in serum of mice
      treated with carbon tetrachloride.
AB  - The physicochemical and biological properties of a mouse hepatocyte growth
      stimulating factor (mHGSF), whose amount in mouse serum increased markedly 24 h
      after carbon tetrachloride administration (E. Gohda et al., Life Sci. 46, 1801
      (1990)), were examined. This factor was a heat-labile protein with a molecular
      weight of 75000. Its activity was sensitive to disulfide reduction. Maximal
      stimulation of deoxyribonucleic acid synthesis in cultured rat hepatocytes by
      this factor was greater than that by acidic fibroblast growth factor (acidic FGF)
      or mouse epidermal growth factor (EGF) and was comparable to maximal stimulation
      by human hepatocyte growth factor (hHGF), a heterodimer with a molecular weight
      of about 85000. The effect of mHGSF was additive to the maximal effects of acidic
      FGF and EGF and was synergistic with the maximal effect of insulin, but was
      neither additive nor synergistic with the maximal effect of hHGF. The mHGSF
      activity was not inhibited by a neutralizing anti-hHGF antiserum, which
      recognizes nonreduced hHGF but not reduced heavy and light chains of hHGF. mHGSF
      did not show any cross-reactivity to anti-hHGF monoclonal and/or polyclonal
      antibodies as measured by an enzyme-linked immunosorbent assay for hHGF. These
      results suggest that mHGSF is a hHGF-like factor with some structural difference
      from hHGF.

PMID- 1376643
TI  - Comparison of flanking regions of the 5S ribosomal ribonucleic acid genes in
      Leptospira biflexa and Leptospira interrogans.
AB  - One of the genes encoding the 5S ribosomal ribonucleic acid (rRNA) for the
      Leptospira biflexa strain Patoc I was isolated and sequenced. The physical maps
      of the 5S rRNA genes in Leptospira were constructed. The strains of Leptospira
      biflexa had two genes on their chromosome; these two 5S rRNA genes were located
      several kb apart and sequences flanking these genes were divergent. In contrast
      to saprophytic leptospires, maps in parasitic leptospires that had only one gene
      for 5S rRNA on their genome were highly conserved and the physical maps of the
      genes in almost all strains were similar.

PMID- 1376644
TI  - Permeability of rat atrial endocardium, epicardium, and myocardium to large
      molecules. Stretch-dependent effects.
AB  - Atrial distension, which stimulates atrial natriuretic peptide secretion by
      atrial myocytes, also stretches nonmuscle cells. In a noncontracting in vitro
      preparation of combined right and left atria we demonstrated by electron
      microscopy that, at 37 degrees C, transition from zero pressure to a
      physiological distending pressure of 5.1 mm Hg rapidly rendered atrial
      endocardial endothelium permeable to the macromolecular probes horseradish
      peroxidase (HRP; M(r), approximately 40,000) and wheat germ agglutinin-HRP (M(r),
      approximately 70,000); each probe was introduced at the atrial cavitary
      endocardial surface. Stretch-dependent permeabilization was also demonstrable in
      spontaneously contracting atria, was reversed by removing the distending
      pressure, and was unaffected by varying external Ca2+ concentration from 0.2 to
      1.4 mM or by experimental perturbations that markedly decrease ANP secretory
      rates. Although transendocardial HRP and wheat germ agglutinin-HRP passage
      required stretch, native ferritin (M(r), = 500,000) could traverse unstretched
      endocardium. Probes were detected in noncoated endocardial vesicles and
      intercellular junctions between endocardial cells, but the relative contributions
      of vesicular transcytosis and paracellular diffusion could not be determined.
      Although HRP entered plasmalemmal caveolae of myocytes in stretched atria,
      myocytes did not internalize HRP by fluid-phase endocytosis. Distending pressure
      also caused apparent flow reversal in thebesian blood vessels, with retrograde
      transfer of HRP across the endocardium into the myocardium. HRP and ferritin
      presented at the external surface of the epicardium (visceral pericardium) were
      endocytosed by mesothelial cells, entered junctions between mesothelial cells,
      and readily crossed the epicardium of both stretched and unstretched
      preparations.

PMID- 1376646
TI  - Developmental expression of the 3-fucosyl-N-acetyl-lactosamine/CD15 epitope by an
      olfactory receptor cell subpopulation and in the olfactory bulb of the rat.
AB  - In the olfactory epithelium a subpopulation of receptor cells were CD15 (3
      fucosyl-N-acetyl-lactosamine)-positive at their somata and their processes.
      Cytomorphology and location implied their mature character. The labeled neurons
      were associated with olfactory cilia and showed a unique distribution within the
      olfactory epithelium and a remarkable numerical change during postnatal ontogeny.
      The axons of the marked olfactory receptor cells possibly play a role in guiding
      other axons to their appropriate targets in the olfactory bulb. In the olfactory
      bulb immunoreactivity was predominantly found in the glomerular and in the
      external plexiform layer and showed an age-related shift from the superficial to
      the deep layers.

PMID- 1376645
TI  - Tangential neuronal migration in the avian tectum: cell type identification and
      mapping of regional differences with quail/chick homotopic transplants.
AB  - This paper is a sequel to a previous report, using quail/chick chimeras with
      partial tectal transplants, in which a tangential invasion of host (chick) tectal
      territories by cells originating in the quail graft was demonstrated. The cells
      displaying this secondary tangential migration appeared restricted to two strata
      (stratum griseum centrale (SGC) and stratum griseum et fibrosum superficiale
      (SGFS)). Here we describe the morphology of the tangentially displaced neurons,
      as well as their overall distribution in the host tectal lobe, by means of an
      antibody that specifically recognizes quail cells, staining them in a Golgi-like
      manner. Neurons that migrated into the SGC are identified as multipolar
      projection neurons, typical of this stratum. The majority of cells that migrated
      into the SGFS correspond to horizontal neurons, as was also corroborated by
      observations in Golgi-impregnated material. These horizontal cells are
      concentrated in laminae b, d and f, where their processes form well delimited
      axonal plexuses. In confirmation of previous results, SGC neurons have a limited
      range of migration, whereas SGFS cells translocate across much longer distances.
      In reconstructions of appropriate cases, a remarkable polarity was noted.
      Significant invasion of chick tectum by quail cells mostly occurred in the
      rostral half of the host tectum. The long-range migration of superficial
      horizontal cells frequently reached, but did not cross, the rostral tectal
      boundary. Conversely, tangential migration in the caudal half of the host tectum
      was scarce and coincided with a typical arrangement of quail-derived radial
      columns interdigited with chick-derived columns. These findings are discussed in
      relation to existing data on immature neuronal populations, molecular marker
      distribution and polarity of the avian optic tectum.

PMID- 1376647
TI  - Characteristics of the interactions between acid glycosaminoglycans and proteins
      in normal human plasma as revealed by the behaviour of the protein-polysaccharide
      complexes in ultrafiltration and chromatographic procedures.
AB  - Acid glycosaminoglycans were isolated from normal human plasma: (a) following
      fractionation of plasma (with protease inhibitors) on Sephadex G-200; (b) by
      ultrafiltration through membranes with retention of molecules above 50 kDa, with
      and without previous addition of NaCl, Triton X-100, urea, or guanidine HCl; (c)
      by filtering on Ecteola-cellulose either untreated plasma or after treatment with
      NaCl, urea, Triton X-100, papain or NaOH. More than 95% of plasma
      glycosaminoglycans interact with plasma proteins to give complexes that exhibit
      reproducible behaviour on Sephadex G-200 and are retained by ultrafiltration
      membranes, which the 12-20 kDa polysaccharide chains do filter. High charge
      plasma glycosaminoglycans show ionic interactions with proteins, while low charge
      glycosaminoglycan interactions are resistant to Ecteola charged groups, to 0.5%
      Triton and 4 M urea, while not to 4 M guanidine HC1. Some glycosaminoglycan
      protein complexes appear resistant to proteolysis, suggesting that they may
      originate from lymphocytes. The simple method utilized for plasma GAG measurement
      may represent an useful tool in clinical practice.

PMID- 1376648
TI  - Determination of fetal hemoglobin by cation exchange liquid chromatography.
AB  - A sensitive liquid chromatographic method for the analysis of the major component
      of fetal hemoglobin (HbF0) in blood using high-resolution strong cation exchange
      column is described. The imprecision of the method was assessed in 20 repeated
      assays of blood samples containing 0.67%, 0.97%, 2.2% and 3.3% of HbF0. Within
      assay CVs were 5.0%, 2.8%, 1.8% and 1.5% and between-assay CVs 5.8%, 3.7%, 1.9%
      and 2.7%, respectively. The HbF0 concentration was stable in EDTA blood for at
      least 20 days at +8 degrees C and 3 days at +22 degrees C. Blood HbF0 levels
      (mean +/- S.D.) were 0.41 +/- 0.20% for 21 healthy males, and 0.48 +/- 0.19% for
      22 healthy non-pregnant females. The method is simple and reproducible, and
      allows the sensitive determination of blood HbF0.

PMID- 1376650
TI  - Reference intervals for alpha 1-microglobulin in urine.

PMID- 1376649
TI  - Serum alpha 1-antitrypsin in patients with hepatocellular carcinoma.
AB  - To evaluate the diagnostic value of alpha 1-antitrypsin (alpha-AT) as a tumor
      marker for hepatocellular carcinoma (HCC), we studied the serum levels of alpha
      AT by rocket immunoelectrophoresis and alpha-fetoprotein (alpha-FP) by
      radioimmunoassay in 46 proven HCC patients, 43 cirrhosis patients and 200 healthy
      blood donors. The mean alpha-AT level of the 46 patients with HCC (4.8 +/- 2.7
      mg/ml) was significantly higher than that of 200 healthy control subjects (1.7 +/
      0.7 mg/ml) (P less than 0.0001). The sensitivity of alpha-AT in 24 patients with
      high level of alpha-FP (greater than 400 ng/ml) and 22 patients with low level of
      alpha-FP (less than 400 ng/ml) were 96% and 64%, respectively. There was no
      substantial correlation between alpha-FP and alpha-AT in the two groups (alpha-FP
      greater than 400 ng/ml, alpha-FP less than 400 ng/ml) (r = 0.078, 0.064). The
      sensitivity for HCC using alpha-FP level alone (greater than 400 ng/ml) was only
      52%, and the sensitivity using alpha-AT level alone (greater than 3.2 mg/ml) was
      76% of the 46 patients. Combining both tests, sensitivity was improved only to
      80%.

PMID- 1376651
TI  - Epitope-specific induction of mesangial lesions with proteinuria by a MoAb
      against mesangial cell surface antigen.
AB  - A MoAb 1-22-3 (IgG3) was produced in mice immunized with rat glomeruli. A
      blotting study indicated the antigen molecule recognized by this MoAb has a
      molecular weight of about 25 kD, which is the same as that of the Thy 1.1
      molecule. This MoAb is capable of inducing the morphological changes similar to
      those induced by anti-thymocyte serum or the anti-Thy 1.1 MoAb, ER4 and massive
      proteinuria in rats by a single i.v. injection. Proteinuria started immediately
      after MoAb 1-22-3 injection and peaked on day 5. Reaction products were detected
      by immunoelectron microscopy in vitro on the limited mesangial cell surface
      facing endothelial cells and in vivo in partially lysed mesangial cells 30 min
      after injection. Unlike the proteinuria-inducing MoAb ER4, reactivity of MoAb 1
      22-3 was detected neither on endothelial cells, epithelial cells, nor along the
      glomerular basement membrane in vivo and in vitro. There is a difference in
      reactivity toward guinea-pig and rabbit materials between MoAb 1-22-3 and the
      commercial anti-Thy 1.1 MoAb (OX7). The antigenic determinant of MoAb 1-22-3 is
      concluded to be a new epitope and only the binding of MoAb 1-22-3 to this epitope
      proved to lead to an abnormal increase of glomerular capillary wall permeability.

PMID- 1376653
TI  - The expression and role in T cell adhesion of LFA-3 and ICAM-2 on human thyroid
      cells.
AB  - Thyroid follicular cells from patients with Graves' disease and Hashimoto's
      thyroiditis express intercellular adhesion molecule-1 (ICAM-1) and this is in
      part responsible for T cell adherence in vitro. To assess the potential role of
      other adhesion molecules in autoimmune thyroiditis, we investigated the
      expression and function of lymphocyte function-associated antigen-3 (LFA-3) and
      ICAM-2 on thyroid cells. Under basal culture conditions, a mean of 22.7% of
      Graves' thyroid cells (n = 8) expressed LFA-3 and this was enhanced by a mixture
      of T cell-derived cytokines and by IL-1, but not by TSH. LFA-3 was also
      demonstrated on Graves' (n = 4) and Hashimoto (n = 2) thyroid cells by
      immunohistochemical staining ex vivo. A small number of thyroid cells (mean 5.5%,
      n = 5) expressed ICAM-2 by flow cytometry but this was not altered by cytokines,
      and ICAM-2 could only be demonstrated on endothelial cells by immunohistochemical
      staining. It seems likely that contamination of primary thyroid cultures by such
      cells accounted for the small number of ICAM-2+ cells found using flow cytometry.
      Almost all of the cultured cells expressing LFA-3 or ICAM-2 also expressed ICAM
      1, as assessed by dual staining. Blocking LFA-1, LFA-3, and ICAM-1 with
      monoclonal antibodies inhibited the adherence of T cells to thyroid follicular
      cells in assays of cell clustering; antibodies against ICAM-2 had no effect.
      These results show that two important adhesion receptor ligands, ICAM-1 and LFA
      3, are expressed by thyroid cells in autoimmune thyroiditis and that these are
      likely to have functional importance in allowing T cells to bind to thyroid cell
      targets. This may play an important role in the initiation and maintenance of
      Graves' disease and Hashimoto's thyroiditis.

PMID- 1376652
TI  - VLA family in rheumatoid arthritis: evidence for in vivo regulated adhesion of
      synovial fluid T cells to fibronectin through VLA-5 integrin.
AB  - Adhesion of T cells to extracellular matrix (ECM) proteins through VLA integrin
      receptors is crucial for lymphocyte trafficking, tissue localization and
      inflammatory function. We have investigated the expression of different VLA
      integrins (VLA-1-5) on peripheral blood (PB) and synovial fluid (SF) T
      lymphocytes from patients with rheumatoid arthritis (RA). Their expression on
      different cell types from synovial membrane (SM) is also reported. The role of
      VLA-4 fibronectin (FN) receptors in the interaction of activated SF T cells from
      RA patients with a 38-kD fragment of FN has been previously demonstrated. Here we
      have focused functional studies on VLA-5 as an alternative FN receptor for RA T
      cells. A significant higher proportion of SF T cells were able to bind to an 80
      kD fragment of FN, containing the Arg-Gly-Asp (RGD) cell binding site, compared
      with PB T cells. This attachment was almost completely inhibited by anti-VLA-5
      MoAbs as well as by RGD peptides. This enhanced capability by SF T cells appears
      to be independent of the level of the surface expression of the receptor and
      correlates better with their activation state as determined by the expression of
      the activation molecule AIM (CD69). The evidence for the expression of VLA
      heterodimers on both SF and SM cells from RA patients suggests the possible
      implication of ECM proteins in mediating and perpetuating inflammation in vivo.

PMID- 1376654
TI  - Immune changes in HIV-1 infection: significant correlations and differences in
      serum markers and lymphoid phenotypic antigens.
AB  - Human immunodeficiency virus type 1(HIV-1) induces extensive immune cell
      alterations which can be detected by changes both in serum levels of soluble
      immune activation products and in several lymphoid phenotypic markers. The
      current studies were conducted in 70 HIV-1 seropositive subjects to determine
      whether changes among four important serum immune activation markers (neopterin,
      beta-2 microglobulin, soluble CD8, and soluble IL-2 receptor) and seven lymphoid
      phenotypic markers (CD38, HLA-DR, CD57, CD11b, CD45RA, leu8, and CD71) reflect
      similar or disparate aspects of immune pathology. On the basis of correlation
      coefficient calculation, four groups of related markers (Fig. 1) were identified:
      Group A, sIL-2R was related to group B where serum neopterin, beta 2M, sCD8
      levels, and lymphocyte CD38 antigen expression correlated closely. Loss of CD45RA
      or Leu 8 antigens in group C correlated with group B and D markers increase. HLA
      D in group D was a more distantly related immune activation marker. Phenotypic
      markers CD57, CD11b, and CD71 did not correlate with the immune activation
      processes reflected by the serum and phenotypic marker groups A-D. Correlations
      between serum and certain lymphoid phenotypic markers were generally stronger
      later in HIV-1 infection when CD4 levels were less than 500/mm3. This study
      provides information for selecting markers for investigating immune changes in
      HIV-1 infection and immune-related diseases. Many serum and lymphoid phenotypic
      markers reflect related aspects of immune dysregulation. However, some markers
      can indicate different aspects of disease.

PMID- 1376656
TI  - [Risks and follow-up of choledocho-jejunostomy for nonresectable cancers of the
      head of the pancreas. A prospective study].
AB  - In 44 patients with palliative operative procedures due to non-resectable
      pancreatic cancer the preoperative risk factors and the intra- and postoperative
      course as well as the long-term results were prospectively investigated.
      Postoperatively 2 patients developed severe complications and 3 patients died.
      The median survival time was 5 months. The results of this investigation show,
      that the biliodigestive anastomosis offers a good palliation in patients with non
      resectable pancreatic cancer. Indication for non-operative palliative procedure
      are patients in poor general condition with a life expectance of less than 4
      months.

PMID- 1376655
TI  - [Analysis of prognosis-associated factors in pancreatic head and peri-ampullary
      cancer].
AB  - Between 1982-1990 we treated 461 patients with adenocarcinoma of the pancreas or
      the periampullary region. 125 (68 ductal pancreatic and 57 periampullary
      carcinomas) of these patients (27.1%) underwent resection. Hospital lethality was
      3.6% (n = 4). Distribution of pT stages (UICC 1987) and frequency of complete
      resection (R0 vs. R1/R2) were significantly different between the periampullary
      and pancreatic tumors. This appeared to be due to the high frequency of pT1/2
      periampullary tumors (49.2%) as compared to the prognostically equivalent pT1
      tumors of the pancreas (1.9%). The absence of lymph node metastases significantly
      improved survival of periampullary tumors. This was not observed in tumors of the
      head of the pancreas. This data indicate that the poor prognosis of ductal
      pancreatic compared to periampullary cancer is primarily caused by their advanced
      stage at the time of diagnosis. In addition current resection techniques only
      inadequately respect the complex lymphatic drainage of the head of the pancreas.

PMID- 1376657
TI  - [Cryotherapy in rectal cancer. A palliative local tumor treatment].
AB  - Cryotherapy was applied to 182 rectal cancer patients in the Department of
      General Surgery, University of Ulm, between 4/1982 and 4/1991. Recipients of this
      tumor freezing therapy were patients whose general condition was bad, patients
      with an advanced inoperable carcinoma, patients with tumor recurrence and
      patients refusing operation. Rectal carcinomas, mostly in an advanced stage, were
      usually freezed several times. Only 4 patients with general inoperability reached
      the survival time margin of 5 years. In 18 patients local tumor destruction was
      possible by application of cryotherapy. In 80% of cases disagreeable tumor
      symptoms like tenesma, mucous discharge and oozing hemorrhages could be reduced
      or completely removed. Perianal pain and intense tumor bleeding could be relieved
      temporarily or definitely in only 50% of patients. An artificial anus could be
      avoided in 80% of cases by local tumor destruction/reduction or arrest of tumor
      growth. The mean survival time of patients with tumor recidivation was 11 months
      after onset of the recurrence. Tumor progression, incontinence and iatrogenic
      rectal perforation made an artificial anus necessary in 14 patients.

PMID- 1376658
TI  - Supportive role of image analysis and DNA ploidy pattern in the diagnosis of
      thyroid tumors.
AB  - To evaluate the supportive role of image cytometry and DNA ploidy pattern in the
      diagnosis of thyroid tumors, a preliminary study was performed on fine needle
      aspirates of 30 cases. Of these, 10 cases each were of colloid goiter, follicular
      neoplasm, and papillary carcinoma. The nuclear area and DNA value of 50 cells in
      each case were measured. The mean nuclear area in colloid goiter (69.50 + 12.62
      sq.microns) was significantly lower than the mean nuclear area in a follicular
      neoplasm (88.71 + 15.51 sq.microns) (P less than 0.05). Similar differences
      between the mean nuclear area in colloid goiter and papillary carcinoma (124.0 +
      12.27 sq microns) was also highly significant (P less than 0.001). The results
      obtained by image cytometry were compared with estimated DNA ploidy pattern of
      follicular cells from the same cases. All colloid goiter had mean nuclear area
      below 100 sq.microns with diploid DNA value. However, papillary carcinoma showed
      aneuploid DNA pattern in eight cases (80.0%), but mean nuclear area was above 100
      sq.microns. A diagnostically useful finding obtained in two of the 10 cases of
      follicular neoplasm was the association of aneuploid DNA pattern with mean
      nuclear area of the follicular cells above 100 sq.microns indicating a high
      probability of carcinoma and thus demanding an urgent open biopsy. These cases
      were readily distinguished from other cases of the same category showing diploid
      DNA pattern and mean nuclear area of follicular cells below 100 sq.microns.

PMID- 1376659
TI  - Identification of Acanthamoeba in bronchoalveolar lavage specimens.
AB  - Acanthamoeba species infect humans occasionally and act as opportunistic
      pathogens in immunocompromised individuals. This study demonstrates the
      application of cytocentrifugation as an aid to identification of Acanthamoebae.
      In addition, certain staining procedures clearly optimized visualization of
      characteristic amoebic features. This was demonstrated by adding amoebae from
      laboratory cultures to bronchoalveolar lavage specimens. In preparations stained
      by the Papanicolaou, trichrome, or hematoxylin-eosin (H&E) procedures, the
      discrete deeper staining nucleolus was the most distinctive feature. The
      vacuolated cytoplasm also aided in the identification of amoebae. These features
      were less apparent and often distorted following staining of Acanthamoeba species
      with the Hema III and Giemsa procedures.

PMID- 1376660
TI  - Assessment of a computer program to detect epileptiform spikes.
AB  - This study compares an automated spike detection program to a group of 6
      electroencephalographers. Since group members varied in experience, an expertise
      factor was devised to weight their scoring. EEGers underscored epileptiform
      events on 6 records in a manner analogous to the computer's storage of EEG
      segments. A summation of expertise factors was determined for every event. This
      sum was normalized and interpreted as a probability the event would be called a
      spike by a given EEGer. The performance of each scorer and of the computer at
      different amplitude thresholds was analyzed based on this probability. Higher
      rated scorers identified more subtle events. Lowering the threshold of the
      computer program produced a comparable increase in sensitivity. The increase in
      total events detected by the computer was linear over the range studied. While
      the proportion of false positive detections increased with lowering threshold,
      our readers have not found a moderate number of these distracting. We conclude
      that the computer system, while not as specific as an EEGer, can be as sensitive
      and can be a reliable screening editor for large amounts of monitoring data. On
      balance it is more effective than an EEGer for this limited purpose.

PMID- 1376661
TI  - State dependent spike detection: validation.
AB  - We present a formal validation of the method of state dependent spike detection;
      its principle and initial results were given in Gotman and Wang (1991). The
      method utilizes different procedures for elimination of non-epileptic transients
      according to state (active or quiet wakefulness, sleep stages); it also varies
      detection sensitivity according to state. Twenty new 100 min recordings were
      obtained from 20 unselected patients, covering active wakefulness, quiet
      wakefulness and various sleep stages. Results indicated that, while the total
      number of detections was reduced by 15%, true detections increased by 39% and
      false detections decreased by 60%. This significant improvement is due to the
      fact that wave morphology is now considered within its spatial context and
      particularly within a wide temporal context.

PMID- 1376662
TI  - EEG changes in patients during the introduction of carbamazepine.
AB  - This study evaluates the EEG changes during the standardized introduction of
      carbamazepine in 16 previously untreated neurological patients and their
      relationship to serum levels of carbamazepine and carbamazepine-10,11-epoxide.
      Therapy was started with a dosage of 400 mg carbamazepine b.i.d. and remained
      unchanged during the whole study period of 35 days. Frequency analysis of serial
      EEG records was performed by Fast Fourier Transformation. In comparison to the
      pretreatment period (1) the mean values of the total power and relative powers of
      the theta and delta bands increased and (2) the mean values of the relative power
      of the alpha band and the center frequency decreased. These changes were already
      established 3 days after the beginning of the treatment and remained constant
      during the observation period. There were marked interindividual differences. (3)
      There was no statistically significant correlation between serum levels of
      carbamazepine or carbamazepine-10,11-epoxide and the EEG parameters. Our results
      demonstrate that the degree of EEG change primarily reflects individual
      susceptibility to carbamazepine and its metabolite during the early stage of
      carbamazepine exposure and is not dose related.

PMID- 1376663
TI  - Quantitative analysis of the EEG during tonic REM sleep--methodology.
AB  - Frequency and amplitude characteristics of the clinical (waking)
      electroencephalogram (EEG) can be diagnostically useful in neuronal degenerative
      disorders such as Alzheimer's or other cortical dementias. However,
      interpretation of the clinical EEG may be limited by many factors, including
      movement and muscle artifacts and uncontrolled variations along the alert/drowsy
      continuum. Moreover, the clinical EEG involves subjective judgement by experts
      whose opinions often differ. In an effort to address these problems, we have
      developed a computer-automated technology that examines the digitized, all-night
      sleep EEG for frequency and amplitude characteristics of potential diagnostic
      relevance to Alzheimer's dementia. Robust time series analysis techniques and a
      modified power spectral analysis (Z-spectra) are used to suppress artifactual
      information and to automatically select samples of tonic REM sleep EEG. The
      spectra (amplitude vs. frequency relationship) of this specific EEG state is then
      assessed for diagnostically relevant information.

PMID- 1376664
TI  - EEG markers of early Alzheimer's disease in computer selected tonic REM sleep.
AB  - All night sleep/wake EEGs were examined for diagnostic features sensitive to
      early Alzheimer's disease (AD) using computer automated techniques. Thirty-nine
      mild AD patients and 43 normal controls underwent 9 h of EEG recording in the
      sleep laboratory. All-night EEGs were screened for ideal, low artifact tonic REM
      sleep using autoregressive and power spectral techniques. The frequency spectra
      during tonic REM sleep revealed a significant shift towards slower wave forms in
      AD vs. control subjects. Beta (greater than 12 Hz) was reduced and theta and
      delta (2-8 Hz) increased in AD compared to control groups. This frequency shift
      was demonstrated by several analytic techniques, including binned spectral
      energies and unique zones in the frequency spectra. Discriminant analyses using
      optimal binned EEG variables correctly classified 74% of AD and 98% of control
      subjects, and unique zone scores correctly classified 92% of AD and 95% of
      control subjects, indicating that these sleep EEG changes are apparently
      predictive of AD status.

PMID- 1376665
TI  - Background EEG reactivity in auditory event-related potentials.
AB  - Mental activity has influences on auditory event-related potentials (AERP) as
      well as on some EEG rhythms, notably the alpha rhythm. In this study, background
      reactivity (BR) of the EEG was investigated in the context of AERPs. Single
      responses of 14 healthy subjects were analysed in 3 reaction time AERP
      experiments of increasing difficulty: the first involved one type of tone
      delivered at random intervals, the second offered two types of tone (an "oddball"
      design), and the third offered 3 types of tone. Averages were formed and
      subtracted from the separate responses to reduce their contribution to the EEG.
      The 1526 msec EEG epoch was divided in 9 overlapping periods, and averaged power
      spectra were calculated for these periods. Changes in area of the delta, theta,
      alpha and beta bands in the course of the epoch were calculated. Background alpha
      and beta activity decreased following infrequent but not following frequent
      tones. The decrease was larger for more difficult tasks and reached a maximum in
      the period in which the AERP P3 and N3 peaks fell. Delta and theta powers showed
      increases rather than decreases; these could be attributed to the contribution of
      AERP activity to total EEG power. No clear relationships were found between the
      amount of background reactivity and peak latencies or reaction times. The
      occurrence of background reactivity, not apparent in an average, shows that the
      averaged AERP reveals only part of the EEG changes related to mental activity.
      Background reactivity proved to be more sensitive to task difficulty than P300
      latency. The results are discussed in the context of the additive model of evoked
      potentials.

PMID- 1376666
TI  - Delayed P3 event-related potentials (ERPs) in thalamic hemorrhage.
AB  - Delayed P3 ERPs were recorded with an acoustic oddball paradigm in 5 patients
      affected by unilateral thalamic hemorrhage. P3 latencies in these 5 patients were
      above the normal mean latency of age-matched controls +2/+3 S.D.s. The P3 delay
      was persistent in serial follow-ups at 6 months from stroke. Normal P3 latencies
      were instead recorded in 4 patients with paramedian hemorrhage not involving or
      only partially involving the thalamus.

PMID- 1376667
TI  - Event-related synchronization (ERS): an electrophysiological correlate of
      cortical areas at rest.
AB  - Oscillations in the alpha and beta bands can display either an event-related
      blocking response or an event-related amplitude enhancement. The former is named
      event-related desynchronization (ERD) and the latter event-related
      synchronization (ERS). Examples of ERS are localized alpha enhancements in the
      awake state as well as sigma spindles in sleep and alpha or beta bursts in the
      comatose state. It was found that alpha band activity can be enhanced over the
      visual region during a motor task, or during a visual task over the sensorimotor
      region. This means ERD and ERS can be observed at nearly the same time; both form
      a spatiotemporal pattern, in which the localization of ERD characterizes cortical
      areas involved in task-relevant processing, and ERS marks cortical areas at rest
      or in an idling state.

PMID- 1376668
TI  - Correlations between verbal memory performance and electrocorticographically
      determined suppression of electrical brain activity in intracarotid amobarbital
      tests.
AB  - As a part of presurgical evaluation, bilateral intracarotid amobarbital
      procedures (IAPs) were performed in 42 patients (84 tests) with long-standing,
      medically intractable complex-partial seizures. During the IAPs,
      electrocorticographic (ECoG) recording was carried out via bilaterally implanted
      subdural electrodes. Five distinct patterns of suppression of electrical brain
      activity were observed: (1) an isoelectric line; (2) a burst-suppression pattern;
      (3) polyphasic waves; (4) high-voltage beta; and (5) low-voltage beta activity.
      Further, two types of specific reactions of the epileptic focus were detectable:
      (1) spike-burst-suppression patterns (SBS; 11 left; 7 right; 6 in both IAPs) and
      amobarbital-induced spikes (7 left; 4 right). ECoG suppression patterns as well
      as SBS and spike induction showed great variability in duration and overall
      occurrence. To determine the influence of these amobarbital-induced ECoG changes
      on results of IAP memory testing, performance in a verbal learning task was
      analyzed according to the ECoG patterns predominant during encoding. In left
      IAPs, it was found that SBS at the beginning of or during encoding had a
      significant negative effect on verbal memory. In right IAPs, verbal memory
      performance improved significantly with the decline of ECoG suppression. Hence,
      verbal memory performance in IAPs is significantly affected by specific ECoG
      suppression patterns and activation of the epileptic focus.

PMID- 1376669
TI  - Rapid stream stimulation and the recognition potential.
AB  - The "recognition potential" is an electrical response of the brain that occurs
      for recognizable, but not for non-recognizable, images. When a recognizable image
      evokes it, the more rostral of a pair of vertically oriented occipital electrodes
      reaches an initial positive peak at about 200-250 msec. Several properties
      distinguish this component of the evoked response from event-related potentials
      such as N2 or P3. A new method of stimulation was devised that evoked the
      recognition potential for recognizable images, but virtually no response of any
      kind for non-recognizable images. This was accomplished by presenting images at
      high rates. Chinese ideographs evoked it for subjects whose native language was
      Chinese, but not for subjects unfamiliar with that language. This showed that the
      recognition potential was not caused by differences in the physical attributes of
      the images per se. Instead, recognizability, as defined by a subject's individual
      learning experience, was the important factor.

PMID- 1376670
TI  - Electrophysiological findings in a case of severe intrathecal baclofen overdose.
AB  - Multimodality evoked potentials were examined in a case of serious accidental
      intrathecal baclofen overdose in a patient who suffered from severe spasticity
      due to a traumatic brain lesion. Electrophysiological findings during, before and
      after the intoxication were compared. Transcranial electrical stimulation up to
      750 V did not evoke any responses in thenar muscles on the first day of
      intoxication. An improvement to normal values was observed within 3 days,
      paralleled by an amelioration of the patient's clinical condition. Cervical
      electrical stimulation was largely unaffected by baclofen. Median nerve
      somatosensory and brain-stem acoustic evoked potentials revealed few or no
      differences during intoxication compared to pre- and post-intoxication responses.

PMID- 1376671
TI  - Demonstration of mismatch negativity in the monkey.
AB  - In humans, deviant auditory stimuli elicit an event-related potential (ERP)
      component, termed "mismatch negativity" (MMN), that reflects the operation of a
      cortical detector of infrequent stimulus change. Epidural auditory ERPs were
      recorded from 3 cynomolgous monkeys in response to soft and loud clicks.
      "Oddball" loud or soft stimuli elicited a long-duration frontocentral negativity,
      peaking at approximately 85 msec, that was superimposed upon cortically generated
      obligatory ERP components. These data suggest that monkeys might serve as a
      heuristically valuable system in which to study the neurochemical and
      neuroanatomical substrates of early context-dependent ERP generation.

PMID- 1376672
TI  - Turn and phase counts of individual motor unit potentials: correlation and
      reliability.
AB  - Different turn algorithms are used for quantitative motor unit potential (MUP)
      analysis. To compare their retest reliability, 420 myopathic and neuropathic MUPs
      were recorded twice and the turn count of the first registration was correlated
      with that of the second. Reliability was best for the algorithm according to
      Willison as compared to the conventionally used algorithms based on amplitude
      criteria for 2 or 3 successive relative extrema. As demonstrated by discriminant
      analysis, an amplitude limit of 25 microV yielded more useful turn counts than a
      limit of 50 microV if myopathic MUPs had to be discriminated from normal MUPs.
      For this discrimination the turn count was superior to the phase count which did
      not further improve the discriminant model. This was different for the
      discrimination between normal and neuropathic MUPs. In this case, both parameters
      measured partly independent features of the MUP and had to be considered
      together.

PMID- 1376673
TI  - The influence of muscle length on muscle fibre conduction velocity and
      development of muscle fatigue.
AB  - The influence of muscle (vastus lateralis) length on the muscle fibre conduction
      velocity (MFCV) and on muscle fatigue was studied in 8 healthy volunteers. In
      experiment 1, the electromyographic (EMG) responses were evoked by electrical
      stimulation of the motor point and recorded by a surface electrode array aligned
      along the muscle fibre direction. The MFCV (determined by cross-correlation) was
      measured at knee flexions of 5 degrees (full extension), 45 degrees, 90 degrees
      and 120 degrees with 3 different extension torques. The MFCV declined with
      increasing muscle length and increased with increasing background torque at knee
      flexions from 5 degrees to 90 degrees. From 90 degrees to 120 degrees knee
      flexion of MFCV tended to increase. In experiment 2, the EMG activity at a static
      fatiguing contraction (80% MVC) was measured at 45 degrees and 90 degrees knee
      flexion. The EMG was measured until the subject gave up contracting the muscle
      (endurance). The largest increase in the RMS amplitude and the fastest decreases
      in the mean power frequency (MPF) and MFCV were found at 90 degrees flexion. The
      MVC at 45 degrees knee flexion was 35% lower than at 90 degrees and the time
      until endurance was approximately twice as long for the 45 degrees contraction.
      The results indicate that muscle length is an important parameter for the
      propagation velocity of action potentials and for the development of static
      muscle fatigue.

PMID- 1376674
TI  - Nerve conduction in the hands of vibration exposed workers.
AB  - Symptoms of peripheral neuropathy in the hands are common among workers using
      vibrating tools. The mechanism for this and its relation to carpal tunnel
      syndrome (CTS) was studied in workers exposed to vibration at their workplace
      (17), along with a control group of healthy construction workers with heavy
      manual work but without vibration exposure (10). Patients with uni- or bilateral
      CTS (11) and a group of healthy volunteers without manual work (9) were included
      for comparison. Median nerve conduction velocities were measured both over the
      carpal tunnel and in a more distal segment. Vibration exposed workers had similar
      conduction velocities to unexposed construction workers. The subgroup of
      vibration exposed patients with symptoms from the hands had normal conduction in
      the ulnar nerve but demonstrated a decrease in median nerve conduction comparable
      (but less pronounced) with the CTS group. On a group basis these results
      indicated that the median nerve is most vulnerable for hand-arm vibrations.
      However, the conduction defects were not pronounced enough to diagnose CTS in
      most individual cases.

PMID- 1376676
TI  - Activation of the neck muscles from the ipsi- or contralateral hemisphere during
      voluntary head movements in humans. A reaction-time study.
AB  - Reaction times (RTs) of EMG onset of agonist right and left sternocleidomastoid
      (SCM) and splenius (SPL) muscles in response to acoustic (AC) or unilateral
      somatosensory (SS) stimulation were measured in normal subjects, during head
      rotation (to the right or to the left) and flexion. No significant difference was
      present in the AC-RT of SCM muscles of the two sides between rotations or
      flexion. The same was true for the SPL. Under the tactile condition, in which the
      stimulus was delivered to one index finger, the RTs of both agonist muscles were
      shorter during head rotation toward the stimulus than away from it: the SCM
      contralateral to the stimulated finger was faster than the ipsilateral SCM, while
      the reverse was true for the SPL. During flexion, the SS-RTs of the SCM of both
      sides were similar, and similar in turn to the SCM-RT during rotation away from
      the stimulus. When the stimulus was delivered to the shoulder, the RT difference
      between the agonist SCMs disappeared. The delay in the activation of the SCM
      ipsilateral to the stimulated finger is compatible with the interhemispheric
      transmission time in the absence of callosal connection between the hand areas of
      the primary somatosensory cortex. The data favour the hypothesis that SCM
      activation during voluntary head rotation is controlled by the ipsilateral
      hemisphere.

PMID- 1376675
TI  - Contralateral influences on triceps surae motoneuron excitability.
AB  - In an effort to more fully investigate spinal reflex pathways in humans, we
      measured the isometric force-time curve of the tibial nerve H-reflex in 12
      college age subjects. We also conditioned the reflex with a contralateral H
      reflex stimulus or a contralateral tendon-tap, to ascertain the effects of
      crossed spinal segmental inputs on alpha motoneuron excitability. The
      conditioning stimulus preceded the test reflex by 10, 25, 40, 55, 70, 85, 100,
      115, 130 or 145 msec. The results demonstrate that a conditioning tibial nerve H
      reflex produced marked facilitation onto the contralateral triceps surae
      motoneurons, predominantly at longer-latency intervals. Conversely, a
      conditioning Achilles tendon-tap produced long-latency inhibition to the triceps
      surae. These results demonstrate that differential motoneuron excitability
      changes can be produced by electrical and mechanical conditioning stimuli.
      Moreover, these excitability changes may be long lasting and only appear after a
      relatively long latency. Several neurophysiological mechanisms are proposed to
      contribute to these changes.

PMID- 1376677
TI  - Antagonist muscle inhibition before rapid voluntary movements of the human wrist.
AB  - When a fast voluntary movement is performed from a background condition of
      sustained antagonist muscle activation, there is often a decrease in antagonist
      muscle activity before the onset of the first agonist muscle burst (AG1) that
      continues until the onset of the antagonist muscle burst (ANT). We studied how
      controlling the peak velocity, movement size, and the magnitude of antagonist
      muscle loading affected antagonist muscle inhibition (AntI). AntI was more
      pronounced during movements with lower velocity and greater size, and when
      performed in the direction of heavier background loads, but its variation could
      not be related to any single kinematic or kinetic variable in all circumstances.
      When AntI was larger, ANT was smaller, suggesting that AntI does not play a role
      similar to the premotor silence of the agonist seen before AG1 when the movement
      is made from a background of sustained agonist contraction. When AntI was larger,
      the size of AG1 was also smaller, showing that, according to the motor task,
      different levels of reciprocal inhibition and coactivation occur at the onset of
      the movement. Both AG1 and AntI produce force in the direction of the desired
      movement, and the central nervous system selects an appropriate balance between
      the two, using AntI when possible.

PMID- 1376678
TI  - Motor responses evoked by magnetic brain stimulation in Huntington's disease.
AB  - In 34 patients with manifest Huntington's disease (HD), and in 21 first-degree
      offspring without clinical signs or symptoms, the sizes, central motor latencies
      (CMLs) and variation in latencies of EMG responses (MEPs) following transcranial
      magnetic brain stimulation were studied in muscles of the upper and lower
      extremities. In subgroups of patients and their offspring median and tibial nerve
      somatosensory evoked potentials (SEPs) and electrically elicited long-loop
      reflexes (LLRs) in hand muscles were also investigated. Increased MEP thresholds
      were observed in 10% of the HD offspring, while CML, latency variability and MEP
      amplitudes always lay within normal range. In contrast, SEPs were abnormal in
      33%. In HD patients MEPs were found to be abnormal in up to 72% of patients when
      all available response parameters were taken into consideration. MEP
      abnormalities correlated with the duration of motor symptoms and the severity of
      choreic motor activity. When both MEPs and SEPs were evaluated, abnormalities
      could be detected in 91% of all HD patients. We suggest that abnormal MEPs might
      reflect an altered excitability of the cortico-spinal system as a consequence of
      basal ganglia dysfunction, rather than a structural damage of the investigated
      descending pathways. To localize the pathological mechanism responsible for
      altered LLRs, a "loop analysis" was performed by recording LLRs, MEPs and SEPs in
      the same patients. Alterations of LLRs correlated best with abnormal SEPs and
      might therefore be explained by reduced somatosensory input to the motor cortex.

PMID- 1376679
TI  - Electrical stimulation of motor cortex in experimental cortical ischaemia:
      pyramidal responses at C5 and the surface EMG.
AB  - In 7 baboons maintained under propofol anaesthesia, pyramidal tract responses
      were related to the corresponding peripheral EMG evoked by electrical stimulation
      of the motor cortex under conditions of focal cortical ischaemia. Pyramidal
      responses were recorded epidurally at the C5 level and the EMG was recorded from
      the contralateral hand or foot muscle using subdermal needle electrodes. Cortical
      ischaemia was produced by transorbital occlusion of the common anterior cerebral
      artery, and regional cortical blood flow was measured by the hydrogen clearance
      method. In the normally perfused brain, the later I waves of the C5 response
      required a lower stimulus strength to elicit them than the earlier I1 wave. It
      was more difficult to record the EMG from the hand than from the foot following
      stimulation of the corresponding cortex even though the C5 responses were always
      obtained in both cases. With moderate ischaemia, the later I waves were
      selectively abolished, leaving the D and I1 waves. EMG amplitude was
      significantly correlated with cortical blood flow (r = 0.88, P less than 0.005),
      and the threshold of cortical flow for the EMG was 10-13 ml/100 g/min. Our
      results indicate that changes in amplitude of the late I waves and particularly
      of the EMG are sensitive indicators of cortical ischaemia.

PMID- 1376680
TI  - Magnetic brain stimulation and brain size: relevance to animal studies.
AB  - Magnetic brain stimulation (MBS) is widely used for the investigation of brain
      function in man, but there have been only a few reports of its safety in animals.
      These results were predominantly benign, but the effectiveness of stimulation in
      animals is unclear. Because the stimulators produced obvious motor effects in
      humans, or had a comparable peak magnetic field strength, they were assumed to
      produce comparable electric field intensities and neuronal effects in animal
      brains. We tested this assumption using 3 stimulus coils of different sizes and
      design, plus 6 saline-filled spheres that spanned a range of volume from 0.5 to
      1800 ml. The induced electric field diminished monotonically with decreasing
      radius, by factors of 4.7-6.2 at the extremes of size. Comparable results were
      found using a mathematical model. These results suggest that the efficiency of
      magnetic stimulation is drastically reduced in smaller brains, and that threshold
      and safety studies in some animal models may not be valid.

PMID- 1376681
TI  - The effects of maturation on spontaneous eye movements in the macaque monkey.
AB  - The spontaneous eye movements of infant and adult monkeys were studied both in
      the dark and in the laboratory light by a magnetic search-coil technique and
      analysed comparatively. The spatio-temporal organization of the infant monkey's
      eye movements is predominantly vertical; by contrast it is predominantly
      horizontal in adults. Moreover, the infant monkey's eye movements have smaller
      amplitudes and slower velocities than adult's in both visual conditions. The
      linear relationships between amplitude and maximum velocity suggest that rapid
      eye movements of the infant monkey are saccades but with a lower rate of velocity
      increase than the adult's. We conclude that the eye movements in the infant and
      in the adult monkeys differ in many aspects and that maturation acts on both the
      static and dynamic characteristics of ocular motility.

PMID- 1376682
TI  - Abnormal sympathetic skin responses in thalamic lesions.
AB  - Sympathetic skin responses (SSRs) were abolished in 4 patients affected with
      fatal familial thalamic degeneration involving the anterior (A) and dorsomedial
      (DM) thalamic nuclei, without lesions of the peripheral vegetative system.
      Abnormalities of SSR were not due to peripheral nerve lesions. It is concluded
      that SSR integrity also depends upon thalamic formations ("visceral" thalamus)
      and their frontal cortical connections.

PMID- 1376683
TI  - Western ligand blot assay for human growth hormone-dependent insulin-like growth
      factor binding protein (IGFBP-3): the serum levels in patients with classical
      growth hormone deficiency.
AB  - The insulin-like growth factors I and II (IGFs), important growth factors both in
      vivo and in vitro, are known to have at least six binding proteins (IGFBP-1-6).
      In human serum, IGFBP-3 is a major binding protein and is considered to be GH-IGF
      I-dependent. We have established a Western Ligand Blot (WLB) assay for IGFBP-3.
      The method is a densitometric analysis of IGFBP-3 bands on a film of WLB. The
      IGFBP-3 levels of patients with classical growth hormone deficiency (GHD, 5
      isolated and 10 multiple hormone deficiencies with appropriate therapy) were
      studied. Before puberty there is no overlap between control (n = 31) and the
      patients with GHD (n = 10). However, IGFBP-3 levels of two of five pubertal
      patients with GHD were within the normal range (n = 16). We think that
      measurement of serum IGFBP-3 is a useful diagnostic marker for GHD, especially
      before puberty.

PMID- 1376684
TI  - Thyroid function before and after induced abortion in normal pregnant women.
AB  - We assessed thyroid function before and after induced abortion in 25 normal
      pregnant women. Serum TSH was significantly increased (P less than 0.02), and
      serum hCG-beta was significantly reduced (P less than 0.001) 1 week after induced
      abortion, compared with the levels before induced abortion. There was a
      significant negative correlation between hCG-beta and TSH, and a positive one
      between hCG-beta and FT4 before induced abortion (P less than 0.02). No
      difference was observed in thyroid hormones before and 1 week after induced
      abortion. The results suggest that hCG stimulates the thyroid gland, gaining an
      advantage over TSH, in normal pregnant women.

PMID- 1376685
TI  - Radioimmunoassay for calcitonin gene-related peptide and its measurement in sera
      of patients with thyroid disease.
AB  - To investigate serum levels of calcitonin gene-related peptide (CGRP), we
      developed a sensitive radioimmunoassay (RIA). RIA for CGRP in serum can present
      some problems: the serum may degradate the tracer during incubation and suppress
      the antigen-antibody reaction. We avoided these problems by using aprotinin and
      CGRP-free serum instead of a buffer for the standard curve. We detected serum
      CGRP in all 39 healthy subjects when CGRP-free serum was not used for the
      standard curve, but 34 of these subjects had serum CGRP levels below the
      detection limit (less than 80 pmol/l) when CGRP-free serum was used for the
      standard curve. We defined the normal range for serum CGRP as below 100.8 pmol/l,
      which was the maximum level found in the healthy subjects. We studied serum
      levels of this peptide in patients with thyroid diseases, because the thyroid may
      be one origin of circulating CGRP. Four of 10 patients with medullary thyroid
      carcinoma had elevated serum levels of CGRP. Seven of 24 patients with subacute
      thyroiditis had elevated serum levels of CGRP, but at least one year after
      clinical recovery, CGRP was undetectable in all. Seven of the 37 patients with
      hypothyroidism had elevated serum levels of CGRP. None of the patients with
      hyperthyroidism, adenomatous goiter, thyroid adenoma, or thyroid carcinoma had
      elevated serum CGRP levels. It is necessary to use a standard curve obtained by
      the addition of aprotinin and CGRP-free serum to the assay standards to measure
      serum CGRP levels. Some patients with subacute thyroiditis, hypothyroidism, or
      medullary thyroid carcinoma had elevated serum CGRP levels.

PMID- 1376687
TI  - Substance-P-related and neurokinin-A-related peptides from the brain of the cod
      and trout.
AB  - An extract of the brain of the rainbow trout, Oncorhynchus mykiss contained high
      concentrations of both neurokinin A-like immunoreactivity (corresponding to 90
      pmol mammalian neurokinin A/g wet tissue) and substance-P-like immunoreactivity
      (corresponding to 50 pmol mammalian substance P/g wet tissue) measured by
      radioimmunoassay using antisera directed against the C-terminal regions of the
      mammalian peptides. In contrast, an extract of the Atlantic cod. Gadus morhua
      contained only neurokinin-A-like immunoreactivity (151 pmol/g). This apparent
      paradox was resolved by determination of the primary structures of the fish
      tachykinins. Trout substance P (Lys-Pro-Arg-Pro-His-Gln-Phe-Phe-Gly-Leu-MetNH2)
      has the same amino acid sequence in its C-terminal region as that in the
      corresponding region of mammalian substance P. Cod substance P (Lys-Pro-Arg-Pro
      Gln-Gln-Phe-Ile-Gly-Leu-MetNH2), however, contains a substitution at position 8
      (Phe----Ile) that abolishes reactivity with the antiserum to substance P but
      permits reactivity with the antiserum to neurokinin A. The amino acid sequence of
      cod and trout neurokinin A is the same (His-Lys-Ile-Asn-Ser-Phe-Val-Gly-Leu
      MetNH2) and shows two substitutions (Thr3----Ile and Asp4----Asn) compared with
      mammalian neurokinin A. The data indicate that nervous tissue of teleost fish
      contain tachykinins that are analogous to the peptides found in mammalian
      tissues.

PMID- 1376686
TI  - Production and characteristics of human tissue plasminogen-activator antibodies
      with region-oriented synthetic peptides.
AB  - We selected six peptide sequences as belonging to potential epitopes of tissue
      plasminogen activator (tPA) using, as the main criterion for their choice, the
      location of the peptide sequences on the surface of the protein molecule. The six
      peptides (corresponding to amino acids 4-8, 11-16, 96-101, 272-277, 371-376 and
      514-519) were synthesized, coupled to carrier proteins and injected into rabbits.
      All of these peptides elicited antibodies and 15-75% binding of the corresponding
      iodinated peptide was obtained with a 1:100 dilution of antiserum. Only two anti
      (peptide) sera [anti-(tPA96-101) and anti-(tPA272-277)] reacted with intact tPA
      and its heavy chain in Western immunoblotting analysis. These two peptides
      sequences and fragment tPA11-16 appear to be involved in the structure of native
      antigenic epitopes of tPA, since they were recognized and antibodies present in
      antisera raised against native tPA. There was no interaction between anti-(tPA4
      8) and anti-(tPA371-376) sera with intact one-chain or two-chain tPA. In the case
      of anti-(tPA4-8) cleavage of one-chain tPA to two-chain tPA and reduction of
      disulfide bonds exposed this epitope.

PMID- 1376688
TI  - Localization of the cross-linking sites of RGD and KQAGDV peptides to the
      isolated fibrinogen receptor, the human platelet integrin glycoprotein IIb/IIIa.
      Influence of peptide length.
AB  - The non-covalent and Ca(2+)-dependent heterodimer GPIIb/IIIa, formed by platelet
      glycoproteins IIb (GPIIb) and IIIa (GPIIIa), also known as the integrin alpha IIb
      beta 3, is the inducible receptor for fibrinogen and other adhesive proteins on
      the surface of activated platelets. A fraction of the isolated GPIIb/IIIa in
      solution binds RGD or KQAGDV inhibitory peptides and, upon peptide removal,
      apparently acquires the capacity to bind fibrinogen ('activated' GPIIb/IIIa) [Du,
      X., Plow, E. F., Frelinger, A. L., III, O'Toole, T. E., Loftus, J. C. & Ginsberg,
      M. H. (1991) Cell 65, 409-416]. Photoaffinity labelling was used here to study
      the ligand binding site(s) of GPIIb/IIIa in solution, for which the peptides
      CKRKRKRKRRGDV (alpha 1), CGRGDF (alpha 2), CYHHLGGAKQAGDV (gamma 1) and CGAKQAGDV
      (gamma 2) were synthesized with a photoactivable cross-linker group and a
      fluorescent reporter group attached to the N-terminal cysteine residue. Contrary
      to the situation in activated platelets, both GPIIb and GPIIIa were equally
      labelled by the four peptides and the cross-linking sites were localized by
      protein chemical analyses of the fluorescently labelled tryptic peptides of both
      subunits. Thus, the localization of the cross-linking sites in GPIIb varies
      considerably with the peptide length and is very different from that localization
      observed in activated platelets: alpha 2 and gamma 2 were found cross-linked to
      the N-terminal of both the heavy (GPIIbH 42-73) and the light (GPIIbL2 30-75)
      chains of GPIIb; while the longer peptides alpha 1 and gamma 1 were cross-linked
      to the C-terminal of GPIIbH within the 696-724 and 752-768 peptide stretches,
      respectively. On the other hand, the cross-linking sites of the four inhibitory
      peptides in GPIIIa were found mainly within the proteolysis susceptible region,
      between the N-terminal (GPIIIa 1-52) and the core (GPIIb 423-622) highly
      disulphide-bonded domains, observing that the longer the peptide the closer the
      cross-linking site is to the N-terminal of GPIIIa: alpha 1 at GPIIIa 63-87 and
      303-350; gamma 1 at GPIIIa 9-37; alpha 2 at GPIIIa 151-191; and gamma 2 at GPIIIa
      303-350. These results led us to the following conclusions. (a) The GPIIIa 100
      400 region contributes to the ligand-binding domain in GPIIb/IIIa both in
      solution and in activated platelets.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1376689
TI  - Purification to homogeneity and characterization of a redoxyendonuclease from
      calf thymus.
AB  - A redoxyendonuclease from calf thymus was purified to apparent homogeneity. The
      redoxyendonuclease recognized and induced cleavage of DNA damaged by ultraviolet
      light. The enzyme preparation produced a single band of a relative molecular mass
      of approximately 34 kDa upon SDS/PAGE. The apurinic/apyrimidinic endonuclease and
      the DNA glycosylase activities remained associated in the apparently homogeneous
      preparation of the enzyme. The redoxyendonuclease activity displayed a broad pH
      optimum between pH 5.0-8.5 and exhibited no requirement for divalent cations. By
      application of FPLC columns Mono-S, Mono-Q and Mono-P, the isoelectric point (pI)
      of the enzyme was found to be approximately 8.0. Using the DNA sequencing
      procedure of Maxam and Gilbert [Maxam, A. M. & Gilbert, W. (1980) Methods
      Enzymol. 65, 499-560] the purified enzyme was found to incise ultraviolet-light
      irradiated DNA at pyrimidine sites as observed previously with a more crude form
      of the enzyme. While the most frequently cleavaged sites for the crude
      preparation were at cytosine residues, the apparently homogeneous enzyme
      preparation frequently induced cleavage sites at both cytosine and guanine
      residues. Predominant incision induced by the apparently homogeneous preparation
      was observed at guanine residues when a particular DNA sequence was used as
      substrate. Furthermore, the 16 N-terminal amino acid residues of the purified
      enzyme were identified. The sequence did not show any significant similarity to
      other known proteins.

PMID- 1376691
TI  - Comparative study between the use of a treatment with hyperthermia through the
      rectal approach versus the urethral approach for benign prostatic hyperplasia.
AB  - 200 patients suffering from benign prostatic hyperplasia were treated with
      hyperthermia: 100 cases through the rectal approach and 100 through the urethral
      approach. Subjective symptoms were assessed as well as nycturia and objective
      data, urinary flow and postmicturition residue before treatment and 6 months
      after treatment. In the group of 100 patients treated rectally, the subjective
      symptoms and nycturia improved in 76; urine flow improved in 63, postmicturition
      residue decreased in 32 and the vesical catheter could be removed in 5 out of 8
      patients. With the urethral approach, 77 patients out of 100 presented an
      improvement in their symptoms, nycturia improved in 53; urine flow improved in
      28; the urine residue was decreased in 40 and the vesical catheter could be
      removed in 10 out of 16 patients who required it previously. Although slightly
      better results seem to be achieved with the use of rectal hyperthermia, as
      concerns nycturia and micturition flow, we prefer the urethral approach for its
      higher degree of convenience, easier handling, shorter time of treatment and
      reasonable effectiveness.

PMID- 1376690
TI  - Differential tissue-specific expression and induction of cytochrome P450IVA1 and
      acyl-CoA oxidase.
AB  - We have examined the tissue-specific expression and inducibility of acyl-CoA
      oxidase and cytochrome P450IVA1 (P450IVA1) RNA in rats. Groups of three rats were
      dosed daily by gavage with methylclofenapate at 25 mg/kg in 5 ml/kg corn oil for
      nine weeks, or were administered a vehicle control. P450IVA1 and acyl-CoA oxidase
      RNA were detected using an RNase protection assay. Similar levels of acyl-CoA
      oxidase RNA were present in control liver and kidney, but the level of this RNA
      in lung, muscle and testis was 6-11%, and in pancreas was 0.13%, of that in
      liver. Treatment of rats with methylclofenapate led to an 11-fold induction of
      acyl-CoA oxidase RNA in liver and also produced a significant induction of this
      RNA in kidney, lung, muscle and testis of 1.7-fold, 1.3-fold, 2-fold and 1.7
      fold, respectively. Acyl-CoA oxidase RNA was not induced in pancreas. P450IVA1
      RNA was present in control liver and also in kidney of control rats at 28% of the
      level in liver. In contrast to acyl-CoA oxidase RNA, P450IVA1 RNA was not
      detected in lung, pancreas or testis. Methylclofenapate treatment of rats led to
      an 18-fold induction of P450IVA1 RNA in liver, and a sevenfold induction in
      kidney. Induction of P450IVA1 was not detected in any of the other tissues
      examined. Quantification of the relative amounts of acyl-CoA oxidase and P450IVA1
      RNA in control liver revealed that acyl-CoA oxidase RNA was present in a 17.5
      fold molar excess over P450IVA1 RNA. Western blotting with an anti-P450IVA IgG
      revealed two bands of similar apparent molecular mass in liver and kidney
      microsomes, but not in microsomes from the testis of control rats.
      Methylclofenapate treatment of rats caused an increase in the intensity of these
      bands in microsomes from liver, but no induction was obvious in kidney.
      Immunocytochemical staining for both the microsomal P450IVA and peroxisomal acyl
      CoA oxidase proteins was restricted to the proximal convoluted tubule in the
      kidney cortex, with staining being most intense in the S3 region.

PMID- 1376692
TI  - Value of biochemical markers in the management of disseminated prostatic cancer.
AB  - The biochemical markers alkaline phosphatase (Alk P), prostatic acid phosphatase
      (PAP) and prostate-specific antigen (PSA) were measured 3-monthly in 61 patients
      with disseminated prostatic cancer who were treated with LHRH analogues. The
      decrease in Alk P and PSA during the first 6 months of treatment was
      significantly related to a better survival. In this follow-up study, only PSA was
      useful for monitoring prostatic cancer during hormonal treatment. Before it was
      visible on a bone scan, PSA gave an indication of tumor progression. PSA might
      permit omission of routine bone scanning. Consensus must be obtained about the
      cost-saving use of biochemical markers in the treatment of disseminated prostatic
      cancer. With the number of treatment options increasing, objective measures are
      of utmost importance. Biochemical markers can be used for prognosis and
      monitoring of the treatment of patients with disseminated prostatic cancer.

PMID- 1376693
TI  - Advantage of systematic random ultrasound-guided biopsies, measurement of serum
      prostate-specific antigen level and determination of prostate volume in the early
      diagnosis of prostate cancer.
AB  - Two hundred and sixteen patients, presenting with a suspicious digital
      examination (stage T3 excluded) or a level of prostate-specific antigen (PSA)
      greater than or equal to 2.5 ng/ml, assessed by radioimmunoassay, underwent a
      transrectal ultrasound examination. Prostate volume was systematically calculated
      and correlated to PSA level. Biopsies were performed: (1) on suspicious
      peripheral hypoechoic areas; ultrasound-guided biopsies; (2) systematically on
      the 2 prostate lobes, whatever the result of transrectal ultrasound
      imaging:random systematic ultrasound-guided biopsies. In the 186 patients who had
      never undergone prostate surgery, ultrasound-guided biopsies showed 42 prostate
      cancers and random systematic ultrasound-guided biopsies showed 75; 14 of the 76
      patients with normal digital rectal examination and transrectal ultrasound
      imaging had a prostate cancer. In the 30 patients who had previously undergone
      surgery for benign prostatic hypertrophy, random systematic ultrasound-guided
      biopsies showed 18 prostate cancers, 13% more than ultrasound-guided biopsies;
      75% of patients with a serum PSA greater than 5 ng/ml had a prostate cancer. A
      very significant correlation was found between PSA level and prostatic volume (p
      less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376694
TI  - Effect of neutral endopeptidase inhibitor on airway function and bronchial
      responsiveness in asthmatic subjects.
AB  - We determined the effect of an inhibitor of neutral endopeptidase, acetorphan, on
      the skin responses to substance P and on the bronchostrictor effects of sodium
      metabisulphite aerosol in asthmatic subjects. One hour following ingestion of
      acetorphan (200 mg) or placebo tablets, cutaneous responses to substance P were
      performed in four subjects. In seven subjects, bronchial challenge with
      increasing concentrations of sodium metabisulphite solutions was performed and
      the concentration required to cause a 20% fall in baseline FEV1 determined
      (PC20). On the acetorphan day, there was a significant increase in the wheal and
      flare responses to substance P and to the diluent (0.9% NaCl) alone. However,
      there was no significant effect of acetorphan on the PC20 metabisulphite. We
      conclude that metabisulphite airway challenge in vivo may not invoke the release
      of endogenous neuropeptides. However, the degree of inhibition of neuropeptide
      breakdown by the oral dose of acetorphan used may not have been optimal.

PMID- 1376695
TI  - The A2 isoform of rat Na+,K(+)-adenosine triphosphatase is active and exhibits
      high ouabain affinity when expressed in transfected fibroblasts.
AB  - The alpha isoforms of the Na+,K(+)-ATPase (Na+ pump) are expressed with
      developmental and tissue heterogeneity in rodents and possess different
      sensitivity to inhibition by ouabain. We directly characterized the ouabain
      sensitivity of the rat A2 (alpha 2) isoform by transfecting NIH 3T3 cells with
      rat A2. The treated cells exhibit high affinity (40 nM) ouabain binding with a
      density of 2 pmol/mg protein. 86Rb+ flux studies confirm that A2 is functional in
      this system and that A2 is inhibited by submicromolar concentrations of ouabain.
      These findings are consistent with measurements of ouabain affinity in tissues
      which express the A2 isoform.

PMID- 1376696
TI  - Differential regulation of insulin-like growth factor binding protein (IGFBP)-2
      mRNA in liver and bone cells by insulin and retinoic acid in vitro.
AB  - Isolated cells produce insulin-like growth factors (IGFs) and their binding
      proteins (IGFBPs). Two distinct cell types were studied with regard to IGFBP-2
      expression: (i) rat hepatocytes, which produce IGF I at a high rate and thus
      regulate its plasma concentration; and (ii) rat osteoblasts, which are targets of
      IGF I action. IGFBP-2 expression is low in hepatocytes prepared from normal adult
      rats and high in calvaria cells from newborn rats. Retinoic acid stimulates IGFBP
      2 production by liver cells. Insulin suppresses both basal and retinoic acid
      induced IGFBP-2 mRNA expression in hepatocytes and has no such effect on
      osteoblasts. Retinoic acid and insulin regulate IGFBP-2 expression in a tissue
      specific manner.

PMID- 1376697
TI  - Bleomycin-detectable iron in the plasma of premature and full-term neonates.
AB  - The bleomycin assay measures non-transferrin-bound iron, able to catalyze free
      radical reactions, in human plasma. No bleomycin-detectable iron is present in
      plasma from healthy adults. However, plasma from 3/15 premature babies was
      positive in this assay. Plasma from 52 apparently-healthy term babies was
      analyzed and 11 were positive in the bleomycin assay. Hence not only some
      premature but also some full-term apparently-healthy babies may be at risk of
      severe oxidative damage.

PMID- 1376698
TI  - Do antigenic peptides have a unique sense of direction inside the MHC binding
      groove? A molecular modelling study.
AB  - In the models suggested recently for antigenic peptides binding in the alpha 1,
      alpha 2 groove of MHC class I molecules, the orientation of the peptide has been
      shown uniquely as: the N----C vector of the peptide being parallel to the N----C
      vector of the alpha 1 helix of MHC. Here, we demonstrate that the reverse
      orientation of the peptide is equally probable. This hypothesis is supported by
      molecular modelling calculations and computer graphic analyses on a murine class
      I MHC molecule H-2Kd and its complexes with a restricted peptide RYLENGKETLQ.
      Analysis of the complementary interactions between the peptide residues and the
      amino acid side chains lining the MHC groove shows that the binding orientation
      of the peptide may be allele-specific and could depend on the sequence and
      structure of the antigenic epitope.

PMID- 1376699
TI  - DNA fingerprints of Bombyx mori L. Testing of genotypic variability of
      parthenogenetic strains.
AB  - A comparative analysis of the total cellular DNA in certain parthenogenetic
      specimens of the silkworm (Bombyx mori), produced from the females of the
      parthenogenetic strains by two types of parthenogenesis, has been performed
      through the application of the DNA fingerprinting method based on M13 phage DNA
      as a hybridization probe. It has been shown that parental specimens and their
      genetically identical off-springs produced through ameiotic parthenogenesis have
      identical patterns of hybridization with the hypervariable DNA fragments. The off
      springs produced through the meiotic type of parthenogenesis have individual
      specific patterns of hybridization, revealing a high level of polymorphism of
      individual genotypes. The results obtained testify to the effectiveness and
      reliability of this promising method for identification of genotypic variability,
      marking and genomic characterization of parthenogenetic clones in the silkworm.

PMID- 1376700
TI  - Zinc causes tyrosine phosphorylation of hippocampal p60c-src.
AB  - Zinc cations at concentrations of 0.2 mM and greater catalyzed specific
      phosphorylation, by ATP, of two membrane-associated proteins from rat
      hippocampus. These proteins, corresponding to molecular weights of 60 and 49 kDa,
      were phosphorylated primarily at tyrosine residues. The 60-kDa protein was
      identified as p60c-src by immunoprecipitation using two different p60src-specific
      monoclonal antibodies. The 49-kDa protein co-immunoprecipitated with p60c-src.
      Cyanogen bromide cleavage of p60c-src and the 49-kDa protein phosphorylated in
      the presence of Zn2+ gave different patterns of phosphopeptides. It is suggested
      that tyrosine phosphorylation of p60c-src and the p60c-src-associated 49-kDa
      protein may be a way of zinc participation in hippocampal neurotransmission.

PMID- 1376701
TI  - Cryosurgery for locally recurrent rectal cancer.
AB  - Locally recurrent rectal cancer is, in most cases, unresectable and incurable.
      Palliative treatment is warranted in many cases because of the presence of severe
      distressing symptoms. In recurrent disease, intraluminal cryotherapy is an option
      for palliation. Twenty patients with local recurrence after anterior resection
      were treated palliatively with cryosurgery for their local symptoms. Six patients
      had previously had a colostomy before they were referred for palliative
      treatment. Thirteen patients had more than one symptom. Distant metastases were
      present in ten cases. The beneficial effect of cryosurgery was evident after two
      to three sessions. In nine patients cryotherapy achieved complete relief of local
      symptoms. In these patients the symptom free interval varied from 1 to 24 months
      (median 11 months); five patients died of disease without local symptoms. Three
      of these nine patients underwent a bowel diversion at a later stage because of
      complete stenosis. The number of treatment sessions in this group of patients
      varied from three to 14. The palliative index varied from 37 to 100% (mean 78%).
      In nine patients cryotherapy of the local recurrence gave no relief at all. Our
      results show that in almost half of the patients cryosurgery can palliate local
      complaints resulting from recurrent tumor growth after anterior resection.

PMID- 1376702
TI  - Anti-CD3 immunotoxin prevents low-dose STZ/interferon-induced autoimmune diabetes
      in mouse.
AB  - Autoimmune diabetes was induced with an established model in which 3 daily
      injections of 95 mg/kg body wt/day streptozocin (STZ) and 2 x 10(4) U interferon
      gamma (IFN-gamma) were administered to C57BL/6 mice. Diabetes onset was
      accompanied by precipitous increases in serum glucose levels and validated by
      immunoperoxidase studies showing diminished islets in pancreatic tissue sections.
      Administration of two to three doses of a monoclonal antibody (MoAb) or an
      immunotoxin (IT) directed against the CD3 epsilon-chain before STZ/IFN-gamma
      treatment prevented increases in serum glucose and protected islets from damage.
      IT was made by crosslinking anti-CD3 to a low oligosaccharide-containing fraction
      of purified ricin toxin A chain (RTA; a catalytic inhibitor of protein synthesis)
      with a stabilized derivative of 2-iminothiolane. Protection was complete, long
      lived, and selective because two different control ITs did not prevent diabetes
      onset. A second pan T-cell-reactive IT was synthesized by linking the MoAb anti
      Ly1 to the same RTA toxin. Anti-Ly1 reacts with the murine homologue of human
      CD5. Anti-Ly1 RTA also protected against diabetes onset in a dose-dependent
      manner requiring higher doses and a longer schedule than anti-CD3 or anti-CD3
      RTA. These studies demonstrate for the first time the importance of CD3+ and CD5+
      cells in diabetes onset in the low-dose STZ/IFN-gamma model and show that anti
      CD3, anti-CD3 RTA, or anti-CD5 RTA may be useful in vivo for the treatment of
      diabetes or perhaps other T-cell-mediated autoimmune diseases. These data may
      have important therapeutic implications for early autoimmune diabetes in humans.

PMID- 1376703
TI  - Focal induction of IGF binding proteins in proximal tubules of diabetic rat
      kidney.
AB  - Diabetes-associated kidney enlargement is associated with increased kidney
      insulinlike growth factor I (IGF-I) binding. IGF-I binds to the type I IGF
      receptor, which mediates most of its actions, and to specific binding proteins
      (IGFBPs), which modulate its actions. To explore the nature and extent of IGF-I
      binding in the kidney, in vitro autoradiography was used to map the distribution
      of IGF binding in control and diabetic rat kidney. Specificity studies were
      performed with increasing concentrations of unlabeled IGF-I, IGF-II, des(1-3)IGF
      I (an IGF-I derivative that binds to receptors normally but with decreased
      affinity to binding proteins), and insulin. In control rats, diffuse binding was
      found throughout the kidney with increased density in the papilla. Binding
      specificity in the cortex and outer medulla was typical of the type I IGF
      receptor (IGF-I = des[1-3]IGF-I greater than IGF-II much greater than insulin).
      Binding in the outer medulla of diabetic kidney was typical of the type I IGF
      receptor. A marked focal increase in proximal tubular binding occurred in 13 of
      22 postpubertal diabetic rats. Binding specificity of the proximal tubular
      binding was consistent with the predominance of an IGF binding protein (IGF-I =
      IGF-II greater than des[1-3]IGF-I with minimal displacement by insulin). Northern
      blot analysis revealed increased IGFBP-1 and IGFBP-3 mRNA in cortical tissue from
      diabetic rats displaying increased proximal tubular binding but not from diabetic
      rats not displaying this phenomenon. As cell surface association of IGFBPs is
      linked to potentiation of IGF activity, a possible mechanism for potentiation of
      local IGF-I action may be provided.

PMID- 1376704
TI  - Aminoguanidine, a novel inhibitor of nitric oxide formation, prevents diabetic
      vascular dysfunction.
AB  - Increased blood flow and vascular leakage of proteins preferentially affect
      tissues that are sites of diabetic complications in humans and animals. These
      vascular changes in diabetic rats are largely prevented by aminoguanidine.
      Glucose-induced vascular changes in nondiabetic rats are also prevented by
      aminoguanidine and by NG-monomethyl-L-arginine (NMMA), an established inhibitor
      of nitric oxide (NO.) formation from L-arginine. Aminoguanidine and NMMA are
      equipotent inhibitors of interleukin-1 beta-induced 1) nitrite formation (an
      oxidation product of NO.) and cGMP accumulation by the rat beta-cell insulinoma
      cell line RINm5F, and 2) inhibition of glucose-stimulated insulin secretion and
      formation of iron-nitrosyl complexes by islets of Langerhans. In contrast, NMMA
      is approximately 40 times more potent than aminoquanidine in elevating blood
      pressure in nondiabetic rats. These results demonstrate that aminoguanidine
      inhibits NO. production and suggest a role for NO. in the pathogenesis of
      diabetic vascular complications.

PMID- 1376705
TI  - Pancreatitis following bile duct sphincter of Oddi manometry: utility of the
      aspirating catheter.
AB  - The aspirating sphincter of Oddi manometry (SOM) catheter was shown to reduce the
      frequency of post-procedure pancreatitis from 31% to 4% following a pancreatic
      duct evaluation. This study was designed to prospectively evaluate the utility of
      the aspirating manometry catheter in reducing the frequency of pancreatic enzyme
      elevation and clinical pancreatitis following isolated bile duct manometry.
      Thirty-eight patients were randomly assigned to undergo bile duct SOM with the
      standard perfusion (infused group) catheter or the aspirating catheter (aspirated
      group). Overall, the frequency of both amylase and lipase level elevation at
      least two times the upper limits of normal was 30% at 2 hours, 25% at 6 hours,
      and 18% at 18 hours after the procedure and was similar for the aspirated and
      infused groups. No episodes of clinical pancreatitis occurred in either group.
      The SOM catheter was perfused with full-strength contrast in 12 consecutive
      patients undergoing a bile duct evaluation. Only one patient had any contrast
      material identified in the pancreatic duct. The results of this study support the
      theory that increased pancreatic duct hydrostatic pressure is the major cause for
      post-SOM pancreatitis and suggests that SOM evaluation of the bile duct alone
      appears to be safe.

PMID- 1376706
TI  - Palliation by laser photoablation: a multidisciplinary quality assessment.
AB  - To evaluate the quality of life and degree of palliation by laser photoablation
      for gastrointestinal cancer, a questionnaire was sent to general practitioners
      (GPs) and referring specialists. The response was 85%. General practitioners
      considered palliation by laser to be effective in 74% compared with 50% for
      referring specialists (p less than 0.001). Specialists felt themselves unable to
      answer in 17% compared with no GPs (p less than 0.001). The differences in
      assessment between specialists and GPs were most pronounced in colorectal
      cancers. There was a striking consensus of opinion about the rate of failed
      palliation among endoscopist, referring specialist, and GP. On the other hand,
      the rating of success by specialists and GPs was significantly lower than the
      endoscopist's evaluation. The endoscopist and GP were more at variance than the
      endoscopist and specialist. Above all, the GPs seemed to outweigh the burden
      against the benefits of treatment. Disagreement of the specialists and the GPs
      with the endoscopist about the outcome appeared to be related to unrealistic
      expectations, to a shift in presenting symptoms or to complications,
      misinterpreted as being laser-induced but mainly due to progression of disease.

PMID- 1376707
TI  - An overtube for upper gastrointestinal endoscopic laser therapy.

PMID- 1376708
TI  - [Palliative laser therapy in gynecologic oncology].
AB  - Local recurrences of carcinomas of the breast and genitals are a severe psychic
      and physical strain on the patients. Continuous confrontation with an often
      visible and generally painful tumour manifestation is an indication for
      palliative treatment, if other oncological therapies can no longer be employed.
      In these cases, the possibility of laser use represents a new therapeutic
      approach. In a pilot study at the University of Heidelberg, Department of
      Obstetrics and Gynaecology, a palliative laser therapy was performed on 45
      patients with locally recurrent carcinomas of the breast (n = 29) and genitals (n
      = 16). Carbon dioxide and Nd:YAG lasers were utilized for tumour resection,
      vaporisation and coagulation. This new concept, the combined application of both
      wavelengths has been proved to be most efficient.

PMID- 1376709
TI  - Effects of tetrahydro-9-aminoacridine on the electrocorticogram of rats with a
      unilateral lesion of the nucleus basalis magnocellularis.
AB  - The effects of tetrahydro-9-aminoacridine (THA) were studied on the
      electrocortical activity of control rats and of rats with a unilateral lesion of
      the nucleus basalis magnocellularis (NBM) produced by alpha-amino-3-hydroxy-4
      isoxozole propionic acid (AMPA). This lesion almost completely deprived the
      lesioned hemisphere of its cholinergic innervation. In control rats, THA (10
      mg/kg i.p.) increased the amplitude of the slow components of the
      electrocorticogram (less than 9 Hz). These effects were antagonised by atropine
      (5 mg/kg i.p.). Lesion of the NBM alone decreased the amplitude of frequencies in
      the 12-16 Hz frequency band but did not significantly affect the slower
      frequencies. THA (10 mg/kg) restored the amplitude of the 12-16 Hz activity to
      the level seen in control rats before THA but did not affect activity in the
      other frequency bands. The results suggest that THA requires some residual
      cholinergic innervation in order to exert its effect.

PMID- 1376710
TI  - Homologous and heterologous adenylate cyclase system desensitization in glial
      cells.
AB  - In the present research the desensitization of adenylate cyclase system induced
      by isoproterenol (IPR), a beta-adrenergic agonist, in primary glial cell cultures
      and the effects of an exposure to 3-isobutyl-1-methylxanthine (IBMX) on the
      response to a subsequent stimulation with IPR have been investigated. A
      pretreatment with the phosphodiesterase inhibitor IBMX induced refractoriness to
      a subsequent IPR challenge suggesting a possible involvement of cAMP in
      heterologous desensitization. Moreover the present results show that IPR
      desensitized cells in confluent cultures retained a normal response to cholera
      toxin, while IBMX treated cells exhibited a reduced response to the toxin. So IPR
      induces a rather specific desensitization while IBMX induced refractoriness seems
      to be non specific.

PMID- 1376711
TI  - [Effect of tranilast, an anti-allergic drug, on the human keloid tissues].
AB  - We studied the inhibitory effects of tranilast, an anti-allergic drug, on the
      human keloid tissues implanted into the dorsal skin of athymic nude mice and on
      the growth of keloid fibroblast in vitro. In the keloid tissue-implanted model,
      tranilast (50-200 mg/kg, p.o.) decreased the weight of the keloid tissue as
      triamcinolone (25 mg/kg, p.o.) did. Tranilast (200 mg/kg, p.o.) reduced the
      hydroxyproline content of implanted tissues. Tranilast (3-300 microM) also
      inhibited the collagen synthesis by keloid fibroblast in vitro. Only a high
      concentration of tranilast (300 microM) suppressed the glycosaminoglycan
      synthesis and cell proliferation of keloid fibroblasts. Moreover, tranilast
      scarcely affected the fibronectin production. Triamcinolone (10 microM) also
      inhibited glycosaminoglycan synthesis and cell proliferation. These results
      suggest that the inhibitory effect of tranilast on the keloid tissues is related
      to its inhibition of the collagen synthesis of fibroblasts. Tranilast would be
      useful as a therapeutic drug for the treatment of keloids.

PMID- 1376712
TI  - [Effect of tranilast, an anti-allergic drug, on carrageenin-induced granulation
      and capillary permeability in rats].
AB  - We studied the effect of tranilast on the growth of carrageenin-induced
      granulation and the increase in capillary permeability induced by inflammatory
      agents in rats. In the carrageenin-induced granulation model, tranilast (50 or
      100-200 mg/kg, p.o.) decreased significantly and dose-dependently the weight and
      the hydroxyproline content of the granulation tissue. Tranilast, however, showed
      no effect on the healing day of locally wounded dorsal skin of rats.
      Triamcinolone (10 mg/kg, p.o.) also showed an inhibitory effect on the
      carrageenin-induced granulation model. Tranilast (50-400 mg/kg, p.o.) dose
      dependently inhibited the enhancement of capillary permeability induced by the Ca
      ionophore A23187, bradykinin and xanthine oxidase. Moreover, tranilast (30 and
      300 microM) suppressed superoxide production induced by FMLP in human
      neutrophils, but did not act as a superoxide scavenger. Considering that
      hypertrophic scar and keloid are conditions characterized by abnormal cell
      proliferation and excessive collagen accumulation accompanied with itch and pain,
      these results suggest that tranilast is useful as a therapeutic drug for
      hypertrophic scars and keloids.

PMID- 1376713
TI  - Comparative effect of truncal vagotomy and pirenzepine on postprandial secretory
      response of exocrine pancreas in dogs.
AB  - The comparative effect of truncal vagotomy and associated pyloroplasty and orally
      administrated pirenzepine (75 mg, 1 h before food intake) on the exocrine
      pancreatic secretory response to food was studied in conscious dogs. Both
      pirenzepine administration and truncal vagotomy totally abolished the pancreatic
      hydromineral and organic secretory response to food intake while postprandial pH
      of intraduodenal content remained above 6. From the results of our study we
      conclude that the vago nerve must not be altered in order to assure a pancreatic
      response to food intake and that pirenzepine is as strong as truncal vagotomy in
      maintaining pH in postprandial intraduodenal content over 6.

PMID- 1376714
TI  - Sclerosing adenosis of the prostate. Report of three cases with
      electronmicroscopy and immunohistochemical study.
AB  - Three cases of rare variant of prostatic adenosis with the features of sclerosing
      adenosis, an uncommon lesion sometimes confused with prostatic carcinoma, are
      reported. The lesions consisted of a small, single nodule in prostates otherwise
      showing typical adenomatous and fibromuscular hyperplasia. The lesions were
      composed of crowded small glands, small solid nests and individual cells embedded
      in a cellular stroma. Immunohistochemistry showed that the glands were lined by
      basal cells positive for the high-weight keratins (EAB-903 and AE-3), a finding
      which confirms the benign nature of the lesion. S-100 protein and smooth muscle
      actin were also positive in the same basal cells suggesting myoepithelial
      differentiation, a character not found in basal cells outside this lesion. This
      finding was confirmed at ultrastructural level by the finding of numerous thin
      filaments in the cytoplasm of basal cells. It is important to recognize this
      lesion in order to avoid confusion with well-differentiated prostatic carcinoma.

PMID- 1376715
TI  - A single human monoclonal antibody that confers total protection from tetanus.
AB  - Protective human monoclonal antibodies (HuMAbs) are superior to hyperimmune sera
      and murine monoclonal antibodies as far as human immunotherapy is concerned. In
      this report, we describe the successful generation of triomas secreting HuMAbs to
      tetanus toxin (tt). Lymphoblastoid cell lines secreting anti-tt antibodies were
      stabilized by back-fusion with a mouse x human heterohybrid myeloma partner, SBC
      H20. One of the antibodies so produced, confers total protection of mice from
      tetanus, unlike a few recent reports where only partial protection (delay in the
      onset of tetanus) was achieved with single HuMAbs. Experiments to localize the
      neutralizing epitope(s) of the toxin using the protective monoclonal antibodies
      revealed that the antibody recognizes a conformational determinant that is
      destroyed on SDS-treatment. Preliminary studies show that Fab preparations of the
      protective antibody are capable of neutralizing tetanus toxin, suggesting that it
      might be possible to clone and express the Fab in a stable vector for large scale
      production.

PMID- 1376716
TI  - Identification of an epitope recognized by the monoclonal antibody PEP80 in the C
      terminal cytoplasmic fragment of glycophorin A.
AB  - The monoclonal antibody PEP80 (IgG1) was raised by immunization of BALB/c mice
      with asialo-agalacto-glycophorin from human erythrocytes. The antibody is
      specific for glycophorin A (GPA) and reacts strongly with the GPA-derived tryptic
      peptide which is the C-terminal cytoplasmic portion of GPA, containing amino acid
      residues 102-131. Using the smaller chymotryptic fragments of this peptide and a
      set of solid phase-synthesized peptides allowed to establish that the MAb PEP80
      is directed against an epitope comprising amino acid residues 112-121 of GPA. The
      peptides terminated with 120th or 119th amino acid residue were slightly less
      active, and the minimal structure which still gave a weak reaction with the
      antibody was the sequence of amino acid residues 112-118. The MAb PEP80 did not
      bind to live human erythroleukemic K562 cells, but showed a strong binding to the
      cells permeabilized with methanol.

PMID- 1376717
TI  - High level expression in E. coli of an alternate reading frame of pS2 mRNA that
      encodes a mimotope of human breast epithelial mucin tandem repeat.
AB  - The high molecular weight mucin found in human milk fat globule and on the
      surface of mammary and other epithelial cells contains a 20 amino acid tandem
      repeat sequence that is highly immunogenic. We have immunoscreened lambda gt11
      cDNA expression libraries from MCF7 cells and lactating breast tissue with 5 anti
      mucin monoclonal antibodies. We isolated a group of cDNA clones that had the
      repeat sequence (HB11-2, HB11-6, HB11-10) and a group that had little or no
      homology with the repeat sequence (NP4, NP5, HB11-4). A fusion protein produced
      by NP4 bound preferentially BrE2, while HB11-4 bound only BrE2 and BrE3, NP5
      produced a fusion protein that bound only Mc5 and not the other MAbs. Sequencing
      of the NP5 cDNA revealed it to be distinct from the mucin sequence and instead to
      have 97% identity with the estrogen induced transcript, pS2. An alternate reading
      frame was translated by the lambda gt11 fusion gene yielding a 44 amino acid
      protein having no homology with pS2 protein. Only a short region of homology (5
      amino acids) with the breast mucin tandem repeat was found which was shown to be
      a mimotope for the Mc5 epitope on the breast mucin. High level expression of the
      NP5 cDNA was achieved by subcloning it into pEX2. The NP5 fusion protein has been
      useful for developing an assay for the presence of mucin derived antigen in
      patient serum.

PMID- 1376718
TI  - Production and characterization of two new mouse monoclonal antibodies reactive
      with denatured mouse class II beta chains.
AB  - We report on the production and characterization of two murine peptide specific
      anti-major histocompatibility complex class II chain specific monoclonal
      antibodies. Two new mouse monoclonal antibodies reactive with two synthetic
      peptides corresponding to Abb amino acids (146-157) and Abs amino acids (146-157)
      were produced. KL295 is the mouse anti-Abb monoclonal antibody, which reacts with
      denatured beta chains of H-2b, H-2d, H-2p, and H-2q, but fail to react with
      spleen cell lysates from H-2f, H-2j, H-2k and H-2s mice. The mouse anti Abs
      monoclonal antibody, KL304 in contrast reacts with the denatured Class II beta
      chains of H-2f, H-2j, H-2k and H-2s mice, but fails to bind H-2b, H-2d, H-2p or H
      2q beta chain, suggesting residues 153-155 of this molecule to be critical for
      the epitope. Both KL295 and KL304 bind B10.WB (H-2j) which suggests a unique
      epitope in this strain of mice. Neither KL295 or KL304 react with native mouse
      class II cell surface molecules.

PMID- 1376719
TI  - Monoclonal antibodies against bacterial glucosamine 6-phosphate synthase:
      production and use for structural studies.
AB  - Fifteen mouse x rat hybridoma cell lines producing rat monoclonal antibodies
      (MAbs) directed to Escherichia coli Glucosamine 6-P Synthase (GlmS) were
      established and characterized. Most of them (13/15) are IgG2a while 2 were typed
      as IgG1. Their Kaff ranged from 1.5 x 10(6) to 9.6 x 10(8) M-1 as determined by
      Beatty et al. (1). The epitopes recognized by these MAbs were assigned to one of
      the two catalytical domains of the enzyme (CT1 and CT2) as demonstrated both by
      ELISA and Western-blotting using purified GlmS proteolytic fragments. The binding
      of the MAbs on either the native or denatured forms of GlmS, CT1 and CT2 was
      further analyzed by competitive immunoassay and most of the MAbs were found to
      bind preferentially to the denatured proteins. The study of the antigenic
      topography of GlmS by competitive radioimmunoassay demonstrated the existence of
      at least 10 independent epitopes on GlmS, divided into three groups. The first
      one (3/15) includes MAbs whose binding was not inhibited by any of the other
      MAbs. The second group (9/15) is comprised of MAbs that exhibit reciprocal
      binding inhibitory activity while the third group includes MAbs (3/15) presenting
      asymmetric inhibitory activity. Finally, since most of the isolated antibodies
      (10/15) bind to the 27 kDa amino-terminal glutamine binding domain (CT2), the
      capacity of these MAb to interfere with the associated glutaminase activity was
      analyzed.

PMID- 1376720
TI  - Characterization of the colorectal antigen IOR-C2.
AB  - A colorectal antigen (IOR-C2) was characterized by a monoclonal antibody produced
      against the colon cancer cell line SW1116. By immunohistochemical staining the
      antigen was abundant and strongly expressed in epithelium of normal colon whereas
      colorectal carcinomas showed a more variable and heterogenous reactivity to the
      antibody (IOR-C2). Radioimmunoprecipitates of SW1116 cell homogenates showed a
      160-200 kD band in SDS gels. Physicochemical characterization indicate that at
      least two IOR-C2 reactive sites are present on the antigen tested and that it is
      mainly an 0-linked glycoprotein carbohydrate chain which can also be N-linked to
      the protein. The expression of IOR-C2 mimics that of the colon associated antigen
      (CAA) and NCC-CO-450 antigen but is distinct from these with regard to its
      expression in carcinomas as well as its physicochemical characteristics.

PMID- 1376721
TI  - Pattern-reversal electroretinographic acuity in untreated eyes with subfoveal
      neovascular membranes.
AB  - To define further the natural history of visual loss in eyes with age-related
      macular degeneration (ARMD) complicated by a subfoveal neovascular membrane,
      pattern-reversal electroretinograms (ERGs) were obtained from patients randomized
      to no treatment at the Dallas center of the Macular Photocoagulation Study (Texas
      Retina Associates). Study eyes (n = 20) were tested during the initial visit and
      at 3-, 6-, and 12-month follow-up visits. Responses were obtained to phase
      alternating checkerboards of varying check size. Extrapolation of the best-fit
      regression line relating the logarithm of the check size to amplitude was used to
      determine "retinal" acuity (log MAR). The pattern-reversal ERG acuity rating (100
      - [50 x log MAR]) was derived for each visit. Pattern-reversal ERG acuity ratings
      for all patients across visits were correlated significantly with visual acuity
      ratings derived from the Bailey-Lovie chart (r = 0.61, P less than 0.001) and
      inversely related to neovascular membrane area (r = -0.55, P less than 0.001).
      During 1 yr of follow-up, pattern-reversal acuity ratings dropped from 53 to 12,
      corresponding to an average decrease of approximately 0.2 octaves/month. These
      results suggest that the pattern-reversal ERG, which samples the resolving power
      of the central 20 degrees, is a sensitive index of visual loss in age-related
      macular degeneration.

PMID- 1376722
TI  - Phase II trial of fazarabine in advanced colorectal carcinoma.
AB  - A total of 15 patients with measurable advanced colorectal adenocarcinoma were
      prospectively treated with fazarabine (Ara-AC), reconstituted in dimethyl
      sulfoxide, and administered at a starting dose of 48 mg/m2/day as a continuous
      intravenous infusion for three days. The dose was repeated every 21 days and dose
      escalations or reductions were made on the basis of toxicities encountered in the
      preceding course. No patient achieved either a complete or partial response.
      Major toxicities encountered were granulocytopenia, thrombocytopenia, nausea,
      vomiting, anemia, and headache. All toxicities were reversible upon
      discontinuation of the drug and no life-threatening toxicities occurred. These
      data indicate that further clinical trials in colorectal carcinoma with this
      agent and schedule of administration are not warranted.

PMID- 1376723
TI  - Phase II trial of fazarabine (ARA-AC, arabinosyl-5-azacytosine) in metastatic
      breast cancer.
AB  - Fourteen consecutive female patients with metastatic breast cancer received a
      total of 31 courses of fazarabine at a dose of 2 mg/m2/hour x 72 hours (48
      mg/m2/day x 3) as a continuous infusion. There were no responses seen, although
      one patient achieved stability of her disease for five courses. Because of
      encouraging in vitro results and the primarily hematologic dose-limiting
      toxicity, further study in combination with colony stimulating growth factors
      might be of interest.

PMID- 1376724
TI  - Magnetic resonance imaging of abscesses using lipid-coated iron oxide particles.
AB  - RATIONALE AND OBJECTIVES: The authors investigated whether iron oxide particles
      can be used as a magnetic resonance imaging (MRI) contrast agent to image
      abscesses in a two-stage experimental design. METHODS: Human buffy coat was
      incubated with iron oxide particles of different sizes and coatings. Smears of
      the incubation mixture were made on a glass slide and stained for iron. The
      percentage of iron oxide uptake was determined by counting 100 neutrophils and
      monocytes and scoring the number of cells that contain iron. Subcutaneous
      abscesses were created in the flanks of 18 Sprague-Dawley rats by injecting them
      with 0.1 mL of turpentine. Iron oxide was given intravenously, and the animals
      were imaged by MRI (1.5 T) 12 to 24 hours later. Different iron oxide coatings
      and doses were compared. RESULTS: The four different types of coating (constant
      fragment [Fc] of IgG, bovine serum albumin [BSA], lipid [Ferrosome], and dextran)
      had an uptake of 72% +/- 5.3%, 61% +/- 6.2%, 30.5% +/- 6.8%, and 5% +/- 2.5%,
      respectively. Comparison of two particle sizes (mean, 90 versus 35 nm) showed the
      large particles to have higher uptake (61% +/- 6.2%) compared with the small
      particles (6% +/- 1.8%) (P less than .001). Post-contrast imaging of the rats
      showed a hypointense ring around the abscess only in the animals injected with
      the lipid-coated agent. The effect was discernible within 12 hours after contrast
      injection and at a dose of 25 mumols iron/kg. Histologic sections showed
      phagocytic cells with iron granules in the periphery of the abscess. No
      hypointense ring on MRI or iron granules on histologic sections was seen around
      the abscess of the control animals or those injected with BSA-iron oxide or Fc
      iron oxide. CONCLUSIONS: Lipid-coated iron oxide particles can be used to image
      abscesses by virtue of their phagocytosis into surrounding inflammatory cells.
      Positive uptake of these particles by human phagocytes in vitro suggests that
      similar results may be applicable in humans.

PMID- 1376725
TI  - Detection and quantitation in rat tissues of the superparamagnetic magnetic
      resonance contrast agent dextran magnetite as demonstrated by electron spin
      resonance spectroscopy.
AB  - RATIONALE AND OBJECTIVES: The compound studies in this article is a
      superparamagnetic macromolecular complex of magnetite cores coated with
      hydrophilic dextran, which is under active investigation as a contrast agent for
      magnetic resonance imaging (MRI) in liver and spleen. The biodistribution of
      paramagnetic compounds is problematic and is usually studied by histochemical
      reactions or by radiolabeling the compound under study. The purpose of this
      article is to show how electron spin resonance (ESR) spectroscopy detects dextran
      magnetite (DM) particles in tissues. METHODS: DM injected intravenously in the
      experimental animal was detected in some reticulo-endothelial organs by ESR. The
      spectroscopic study was validated using electron microscopy and electron-probe
      microanalysis. RESULTS: DM exhibits an ESR spectrum; ESR delineated the
      distribution of DM distribution in liver, spleen, bone marrow, and blood as a
      function of time. The blood clearance was biphasic, dependent on the size of
      particles. CONCLUSIONS: ESR spectroscopy is a highly sensitive and reproducible
      method of studying DM distribution.

PMID- 1376726
TI  - DNA double labelling with IdUrd and CldUrd for spatial and temporal analysis of
      cell proliferation and DNA replication.
AB  - A procedure was developed that very effectively distinguishes between IdUrd and
      CldUrd incorporated in the DNA of cell nuclei and chromosomes. For double
      staining we used the rat anti-BrdUrd monoclonal antibody from Sera-lab that binds
      specifically to CldUrd and BrdUrd but not to IdUrd, in combination with the mouse
      anti-BrdUrd monoclonal antibody from Becton Dickinson. This antibody binds to all
      three halogenated deoxyuridines, but when the nuclei are washed in TRIS buffer
      with a high salt concentration the antibodies linked to CldUrd-labelled DNA are
      removed. When analysing the effect of the deoxyuridines on the cell cycle we
      found that the growth kinetics of Chinese hamster cells were not changed by
      adding IdUrd or CldUrd for 30 min at a concentration of 10 microM, whereas
      adequate double labelling required only 2 min pulses. The effectiveness of the
      technique was demonstrated in two model experiments. The first test concerned the
      assessment of cell recruitment in the central areas of slow-growing clones, after
      addition of fresh medium. The second experiment focussed on the spatial
      resolution of the method. Double-labelled metaphase chromosomes showed
      interspersed green and red replication bands with a spacing corresponding with
      medium resolution Giemsa banding patterns.

PMID- 1376727
TI  - Distribution of taurine in the rat cerebellum and insect brain: application of a
      new antiserum against carbodiimide-conjugated taurine.
AB  - The production, specificity and application of an antiserum against taurine
      conjugated to succinylated ovalbumin by means of 1-ethyl-3(3-dimethylaminopropyl)
      carbodiimide is reported. The antiserum was produced in rabbits. The carbodiimide
      was used also as a tissue fixative. The development of the antibody titre was
      followed by dot-blot tests on nitrocellulose filters using different amino acid
      conjugates and with immunohistochemical reaction in the rat and insect brain.
      Blocking controls were also used. Taurine antiserum, sufficiently specific and
      sensitive, developed after the fourth booster injection, after which the
      antiserum was characterized. In the insect brain, intense taurine-like
      immunoreactivity was observed in the photoreceptors, in the Kenyon cells and the
      neuropile of the mushroom bodies, in the lower part of the central body and in
      the antennal lobes. In the rat carebellum, intense taurine-like immunoreactivity
      was seen in the Purkinje cells. Immunoreaction was seen also in small cells most
      probably corresponding to the basket cells. The use of the carbodiimide in the
      production of antisera against taurine provides a parallel method for comparison
      of the distribution of taurine-like immunoreactivity obtained with antisera made
      against conjugates prepared with aldehydes.

PMID- 1376728
TI  - The distribution of calcium in undecalcified bone as revealed by an improved pyro
      antimonate method.
AB  - The localization of pyro-antimonate-precipitable Ca2+ in the undecalcified femur
      and calvaria of neonatal rats was examined. The fixation of bones with pyro
      antimonate-glutaraldehyde followed by pyro-antimonate-osmium (two-step method)
      resulted in better preservation of tissue and more precise localization of
      precipitates than did the direct immersion of specimens in pyro-antimonate-osmium
      solution (one-step method). The precipitate was frequently observed within the
      endoplasmic reticulum of obsteoblasts. Most vacuoles in osteoclasts contained
      precipitate. By contrast, the mitochondria in these cells were associated with
      small amounts of precipitate. There was no evidence of precipitate in the Golgi
      apparatus. The presence of calcium in the precipitate was verified by EGTA
      treatment and X-ray microanalysis. This study demonstrated that (1) the two-step
      pyro-antimonate method is a useful and reliable procedure for visualizing Ca2+,
      and (2) cellular Ca2- can be successfully localized in undecalcified bone by this
      method.

PMID- 1376729
TI  - Study of prostatic disease in dogs: 177 cases (1981-1986).
AB  - Historical and physical signs associated with prostatic disease diagnosed in dogs
      over a 5.5-year period were defined. One hundred seventy-seven male dogs were
      determined to have prostatic abnormality. Of the 177 dogs, 87 were determined to
      have specific prostatic disease. The most common prostatic disease identified in
      this study was bacterial prostatitis, followed by prostatic cyst, prostatic
      adenocarcinoma, and benign hyperplasia. The most common prostatic disease
      identified in neutered dogs was prostatic adenocarcinoma. Mean age at onset of
      prostatic disease was 8.9 years; statistically significant difference was not
      observed between age at onset of the various types of prostatic disease
      identified. Doberman Pinscher was the most common breed with prostate disease.
      Twenty-nine percent of dogs with a specifically identifiable prostatic disease
      had signs of systemic illness, 41% had signs of lower urinary tract disease, 28%
      had signs of gastrointestinal tract abnormalities, and 13% had signs of locomotor
      difficulty.

PMID- 1376730
TI  - Role of serum vitronectin and fibronectin in adhesion of fibroblasts following
      seeding onto tissue culture polystyrene.
AB  - The suitability of polymeric biomaterials as surfaces for the attachment and
      growth of cells has often been investigated in tissue culture. In this study the
      contribution that adsorption of serum fibronectin (Fn) or vitronectin (Vn) make
      to the attachment and spreading of fibroblast cells during the first 90 min
      following seeding was determined for two modified tissue culture polystyrenes, as
      model biomaterial surfaces. The amount of serum Vn and Fn which adsorbed onto
      tissue culture grade polystyrene (TCP) from different serum concentrations over
      the range of 0.1-30% (v/v) were determined and compared to attachment of cells of
      the BHK-21 and HT1080 fibroblast lines. There was no simple correlation between
      the amount of Fn or the amount of Vn adsorbed and cell attachment and spreading.
      The requirement for Fn or Vn for attachment and spreading of BHK-21 or HT1080
      cells onto modified polystyrene (either TCP or to Primaria) during the first 90
      min of cell culture was directly tested by selective removal of Fn or Vn from the
      serum prior to addition to the culture medium. Attachment and spreading of BHK-21
      or HT1080 cells onto TCP or Primaria surfaces were reduced in a concentration
      dependent manner when the cells were seeded in medium containing 2% (v/v) or
      higher concentrations of Vn-depleted serum. BHK-21 cells or HT1080 cells seeded
      in medium containing Fn-depleted serum (which contained Vn) attached and spread
      onto TCP or Primaria. Both BHK-21 cells and HT1080 cells failed to attach to TCP
      or Primaria when seeded in medium containing serum depleted of both Vn and Fn.
      The requirement for serum Vn or Fn for fibroblast attachment to TCP was also
      tested using cells of a human dermal fibroblast strain. The attachment of the
      dermal fibroblasts to TCP during the first 90 min of culture was not decreased by
      depletion of Vn from the 15% (v/v) serum, but there was a reduction in the
      proportion of the attached cells which had spread. Selective depletion of serum
      Fn did not have any effect on either cell attachment or spreading. Our results
      show that for fibroblast cells, particularly with cell lines such as BHK-21 or
      HT1080 but also with cell strains, the first binding of cells onto tissue culture
      polystyrene when plated in medium containing serum is a result of adsorption onto
      the surface of serum Vn. The adsorption of serum Vn onto the surface overcomes
      the effect of serum components which tend to decrease cell attachment.

PMID- 1376733
TI  - Expression of fibronectin and integrins in cultured periodontal ligament
      epithelial cells.
AB  - The process of attachment of epithelial cells obtained from the porcine
      periodontal ligament (cell rests of Malassez) to different extracellular matrix
      proteins and their expression of fibronectin and integrin receptors were studied
      by means of immunocytochemistry, in situ hybridization, and time-lapse
      cinemicrography techniques. The cell lines of periodontal ligament epithelial
      cells (PLE cells) attached to and spread rapidly on fibronectin, vitronectin, and
      type I collagen. One of the cell lines also attached to laminin, while the other
      cell line showed poor attachment to both laminin and Matrigel, a basement
      membrane material. By use of the in situ hybridization technique, some PLE cells
      were found to express the fibronectin gene strongly. Immunocytochemical staining
      localized fibronectin in extracellular fibrils and intracellular granules.
      Fibronectin was also found in the tracks left behind by the cells migrating on
      the substratum. Arg-gly-asp-ser peptide inhibited the attachment of the PLE cells
      to fibronectin, laminin, type I collagen, and vitronectin by 47%, 43%, 83%, and
      94%, respectively, suggesting that the cell-matrix interactions were partly
      mediated by receptors related to the integrin family. Antibodies against the beta
      1-integrin subunit stained the cell bodies and the plasma membrane projections of
      spreading cells. After 24 h or longer in culture, beta 1-integrins were localized
      to the regions of cell-cell contact. Cinemicrography of the arg-gly-asp-ser
      peptide-treated cells demonstrated that the spreading and migration of isolated
      cells were prevented by the peptide. The peptide did not appear to dissociate the
      cell-cell contacts or interfere with migration of spread-cell colonies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1376732
TI  - Molecular cloning of a novel hyaluronan receptor that mediates tumor cell
      motility.
AB  - A cDNA encoding a unique hyaluronan receptor has been molecularly cloned from a
      lambda GT11 3T3 cDNA expression library. Immunoblot analyses of cell lysates,
      using antibodies to peptides encoded in the cDNA, specifically react with a 58-kD
      protein. This protein is regulated by the mutant H-ras gene in cells containing a
      metallothionein promoter H-ras hybrid gene. Further, antibodies to peptide
      sequences encoded in the cDNA block the increase in locomotion resulting from
      induction of the mutant H-ras gene in this cell line. In a transblot assay, the
      bacterially expressed protein binds to biotinylated hyaluronan. Antibodies to
      peptides encoded in the cDNA react in immunoblot assays with the 58- and 52-kD
      proteins of a novel hyaluronan receptor complex previously implicated in cell
      locomotion. Furthermore, antibodies specific to the 58- and 52-kD proteins, which
      block ras-induced locomotion, also cross-react with the expressed, encoded
      protein. The gene product described here appears to be a new type of hyaluronan
      receptor that is involved in cell locomotion. It is named RHAMM, an acronym for
      receptor for hyaluronan-mediated motility.

PMID- 1376731
TI  - Identification of amino acid sequences in the integrin beta 1 cytoplasmic domain
      implicated in cytoskeletal association.
AB  - Wild-type and mutant chicken integrin beta 1 subunit (beta 1c) cDNAs were
      expressed in NIH 3T3 cells and assayed for localization in focal adhesions of
      cells plated on fibronectin substrates. Focal adhesion localization in stable
      transfected cells was assayed by indirect immunofluorescent staining with chicken
      specific anti-beta 1c antibodies. Mutant beta 1c integrins containing internal
      deletions of 13 amino acids adjacent to the membrane, delta 759-771, and 20
      centrally located amino acids, delta 771-790, localized in focal adhesions
      demonstrating that sequences required for direction to focal adhesion structures
      were not limited to one region of the cytoplasmic domain. Point mutations
      revealed three clusters of amino acids which contribute to localization in focal
      adhesions. These three clusters or signals are: cyto-1 (764-774), cyto-2 (785
      788), and cyto-3 (797-800). The 11-residue cyto-1 signal is only found on
      integrin beta subunit sequences, except beta 4. Four residues within this region,
      D764, F768, F771, and E774, could not be altered without reducing focal adhesion
      staining intensities, and likely form a signal that occupies one side of an alpha
      helix. Mutations involving two cyto-1 residues, K770 and F771, also appeared to
      affect heterodimer affinity and specificity. Cyto-2 (785-788,), NPIY, is an NPXY
      signal that forms a tight turn motif. Cyto-2 provides a structural conformation,
      which when perturbed by proline removal or addition, inhibits integrin
      localization in focal adhesions. Cyto-3 (797-800), NPKY, resembles cyto-2,
      however, the nonconserved proline residue can be replaced without alteration of
      the localization phenotype. Cyto-3, therefore, constitutes a unique integrin
      signal, NXXY. Both serine and tyrosine residues at positions 790 and 788,
      respectively, which have been implicated in integrin phosphorylation/regulation,
      were conservatively replaced without detectable effect on focal adhesion
      localization. However, acidic replacements for these amino acids reduced focal
      adhesion staining intensities, suggesting that phosphorylation at these sites may
      negatively regulate integrin function.

PMID- 1376734
TI  - Human neutrophil-derived histamine-releasing activity (HRA-N) causes the release
      of serotonin but not arachidonic acid metabolites from rat basophilic leukemia
      cells.
AB  - The effects of neutrophil-derived histamine-releasing activity (HRA-N) on
      arachidonic acid (AA) metabolism is unknown. Human basophils exposed to HRA-N
      released 25% of total histamine but no leukotriene C4 (LTC4). To confirm this
      phenomenon, rat basophilic leukemia (RBL) cells were exposed to HRA-N as well as
      anti-IgE, or calcium ionophore A23187. RBL cells incubated with A23187 released
      44% of available serotonin and 59 and 124 pmol/10(6) cells of prostaglandin D2
      (PGD2) and LTC4, respectively. Anti-IgE stimulation resulted in 34% serotonin
      release and the generation of 34 pmol PGD2 per 10(6) cells and 72 pmol LTC4 per
      10(6) cells. In contrast, HRA-N (2 U/ml) induced 20% serotonin release, 4 pmol
      PGD2 per 10(6) cells, and 0.6 pmol LTC4 per 10(6) cells. Neither increasing the
      dose nor the incubation time of HRA-N enhanced the generation of AA metabolite.
      Additionally, the spectrum of AA metabolites generated by RBL cells in response
      to those agents was examined by reverse-phase high-performance liquid
      chromatography. RBL cells stimulated with A23187 released PGD2, LTB4, and its
      isomers, LTC4, and 5-hydroxyeicosatetraenoic acid. In contrast, HRA-N stimulation
      resulted in only minimal PGD2 generation and no other discernable AA metabolites.
      Thus, HRA-N causes selective release of serotonin without inducing AA
      metabolites. These data suggest that HRA-N activates mast cells through a unique
      pathway.

PMID- 1376735
TI  - Chronic idiopathic urticaria: profiles of skin mast cell histamine release during
      active disease and remission.
AB  - Chronic idiopathic urticaria (CIU) is characterized by the increased
      releasability of histamine by mast cells in normal-appearing skin. In active CIU,
      this abnormality is consistently present. To determine if this finding subsides
      when the disease goes into remission phase, we analyzed the histamine secretion
      in patients with CIU in remission (CIUR) compared with that of patients with CIU
      and in normal control (NC) subjects, with the skin-chamber technique. The
      profiles of histamine release in sites challenged with compound 48/80 were
      significantly different in the groups with CIU and CIUR. Furthermore, patients
      with CIUR did not differ from NC subjects in terms of histamine releasability
      under compound 48/80 stimulation (p greater than 0.1). These data suggest that
      the state of excessive skin mast cell sensitivity is a reversible and transient
      phenomenon in CIU disease.

PMID- 1376737
TI  - Re-innervation of submucosal arterioles by myenteric neurones following extrinsic
      denervation.
AB  - We used a combination of selective lesions, immunohistochemistry and video
      monitoring of arteriolar diameter to determine the source of the changes in
      vasodilator innervation to guinea pig ileal submucosal arterioles which occur
      following removal of their extrinsic sympathetic and sensory nerve fibre input. A
      non-cholinergic neurogenic vasodilation appeared in arterioles in which extrinsic
      denervation was performed 50-90 days previously. The non-cholinergic innervation
      did not result from regrowth of extrinsic fibres because the neurogenic response
      was not altered by combining long-term denervation with capsaicin treatment or re
      denervation 7 days prior to examination. However, non-cholinergic neurogenic
      vasodilations were not observed in arterioles which had been subjected to long
      term denervation combined with a myectomy 7 days prior to examination.
      Immunohistochemical co-localization of SP and CGRP in these vessels confirmed
      previous findings that a prominent SP perivascular nerve plexus appeared after
      long-term denervation. Perivascular SP-containing fibres that appeared after long
      term denervation were unaffected by capsaicin or re-denervation but were absent
      from preparations in which long-term denervation and myectomy were performed.
      These results demonstrate that myenteric neurones are the source of the non
      cholinergic innervation which appears after extrinsic denervation and support our
      previous conclusion that SP is the neurotransmitter responsible for this non
      cholinergic vasodilation in submucosal arterioles of the small intestine.

PMID- 1376736
TI  - Measurement of histamine-releasing factor activity in individual nasal washings:
      relationship with atopy, basophil response, and membrane-bound IgE.
AB  - We collected individual pools of nasal washings (NWs) from 15 allergic and 15
      nonallergic subjects to determine histamine-releasing factor (HRF) activity and
      to ascertain the relationship of these cytokines with atopic status, basophil
      releasability, and cell membrane-bound IgE. NWs were concentrated, dialyzed, and
      assayed with basophils from a single donor. Samples from 12 of 15 allergic
      subjects and from all the nonallergic subjects revealed greater than or equal to
      15% histamine release (HR), 33.5% +/- 21.3% (mean +/- SD) and 38.6% +/- 19.6%,
      respectively (p greater than 0.05). When we assayed the same samples with
      autologous basophils, the allergic group demonstrated higher HR than the
      nonallergic group (31.9% +/- 19.7% versus 4.8% +/- 4.3%; p less than 0.001). A
      standard lot of mononuclear cell-derived HRFs was also screened with basophils
      from both groups. Means for HR from basophils of allergic and nonallergic
      subjects were 51.9% +/- 16.7% versus 26.3% +/- 8.2%, respectively (p less than
      0.001). Pretreatment of basophils with lactic acid led to abrogation of
      sensitivity to HRF. Acid-stripped cells incubated with sera from patients with
      asthma regained their capacity to release histamine. We found that HRF activity
      can be detected in NWs of most donors, and there is no difference among allergic
      and nonallergic subjects. Our results suggest that the capacity of these
      cytokines to induce HR depends on several factors: atopic status, basophil
      releasability, and membrane-bound IgE.

PMID- 1376738
TI  - Urinary enzymes excretion in pancreatic diseases. Clinical role and
      pathophysiological considerations.
AB  - The amylase-creatinine clearance ratio was first proposed as a useful tool in the
      diagnosis of acute pancreatitis, and later it was claimed that trypsin creatinine
      clearance ratio was a sensitive and accurate test of pancreatic cancer. More
      recent observations have undermined the role of both clearances in the diagnosis
      of acute pancreatitis, and their utility in patients with chronic pancreatic
      diseases has largely been ignored. Three orders of factors, (a) the
      physicochemical characteristics of the protein, (b) the glomerular filtration
      rate variations, and (c) renal tubular damage, may have a role in determining the
      changes in the plasma-urine transfer of enzymes such as amylase and trypsin.
      Amylase urinary output is related both to variations in amylase serum levels
      (since this enzyme probably is not intensively reabsorbed by the tubule) and to
      the presence of renal tubular damage. Trypsin plasma-urine transfer changes
      depend greatly on the presence of tubular alterations. Elastase 1 and
      phospholipase A2 urinary outputs can also be predicted on the basis of the
      presence of tubular damage. Renal tubular alteration in pancreatic diseases may
      depend on the damaging effect of toxic substances (proteolytic enzymes, for
      example) released by the inflamed pancreas; the role of liver damage and of
      extrahepatic jaundice, which are frequent findings in chronic pancreatic
      diseases, should also be considered. However, toxic compounds such as ethanol,
      which can alter the pancreas and possibly the kidney, could also have a key role
      in the genesis of urinary findings in pancreatic diseases.

PMID- 1376739
TI  - The intraoperative localization of the obscure bleeding site using fluorescein.
AB  - Despite visceral angiography and radiolabeled gastrointestinal scintigraphy, the
      localization of gastrointestinal bleeding can still be a challenge. Even
      preoperative localization with visceral angiography is no guarantee of successful
      intraoperative localization or subsequent pathological confirmation. We report a
      case of obscure gastrointestinal bleeding of small bowel origin, which was
      localized intraoperatively by fluorescein injected via a superselectively placed
      catheter.

PMID- 1376740
TI  - Ashman's phenomenon--a source of nonsustained wide-complex tachycardia: case
      report and discussion.
AB  - The refractory period of the right bundle branch is increased when the R-R
      interval between the prior two conducted impulses is long. Thus, an impulse that
      arrives soon after the second of two impulses separated by a long R-R interval
      may be aberrantly conducted with a right bundle branch block morphology on
      electrocardiogram. This aberrant conduction is termed "Ashman's phenomenon" and
      is often responsible for isolated wide QRS complexes in the presence of
      underlying atrial fibrillation. This process may also produce runs of wide QRS
      complexes that must be distinguished from nonsustained ventricular tachycardia. A
      case of such multibeat Ashman's phenomena is presented, and the characteristics
      used to identify this phenomenon are discussed. A brief review of several recent
      studies on the differentiation of sustained ventricular tachycardia from
      supraventricular tachycardia with aberrancy in the setting of a regular
      underlying rhythm is given as well.

PMID- 1376741
TI  - Techniques to optimize post-embedding single and double staining for amino acid
      neurotransmitters.
AB  - We report a number of technical refinements for single and double staining with
      post-embedding electron microscopy for glutamate, aspartate, and gamma
      aminobutyric acid. Best results were obtained with 2.5% glutaraldehyde in the
      fixative and by minimizing the duration of plastic polymerization and the
      interval between cutting and reacting. Quantitative documentation of the ability
      of exogenous glutamate, aspartate, and gamma-aminobutyric acid to block their
      immune staining is provided. Increased intensity of staining with the glutamate
      and aspartate antisera resulted from preincubation of glutamate antiserum with
      aspartate and aspartate antiserum with glutamate. To perform double staining with
      antisera raised in the same species, it was necessary to block antigenicity of
      the first antiserum; best results were obtained with hot paraformaldehyde fumes.
      By using a detergent instead of etching, these methods permitted the simultaneous
      visualization of tracers to identify neuroanatomic pathways.

PMID- 1376742
TI  - Direct flow cytometric quantification of alkaline phosphatase activity in rat
      bone marrow stromal cells.
AB  - Cell preparations in cytochemistry are conventionally analyzed with transmitted
      light after fixation and reaction with agents such as azo-coupling dyes. With
      cell suspensions stained with fluorescent cytochemical dyes, cells can also be
      analyzed and sorted by flow cytometry. We have exploited the intense red
      fluorescence of Fast Red Violet LB generated in cytochemical reactions to perform
      flow cytometric analyses of alkaline phosphatase (AP) expression in rat bone
      marrow stromal cells. By modifying staining protocols of single-cell suspensions,
      we demonstrate that in comparison to staining with Fast Red TR, the method is
      specific, can distinguish among various levels of enzyme expression within the
      whole population, and permits enzyme kinetic studies of heterogeneous cell
      populations. The method was applied to study the effect of the glucocorticoid
      dexamethasone (Dx) on cell proliferation and AP expression. In low AP-expressing
      cells, Dx treatment at 10(-8) M increased the [3H]-thymidine labeling index from
      3.85% to 5.24% (p less than 0.01). In contrast, high AP-expressing cells were
      unlabeled by [3H]-thymidine. The staining and analytical methods reported here
      facilitate the detection, isolation, and quantification of subpopulations of bone
      marrow stromal cells that express alkaline phosphatase activity. These
      experiments demonstrate the value of flow cytometry as an adjunct to conventional
      cytochemical methods.

PMID- 1376743
TI  - Preservation of cartilage matrix proteoglycans using cationic dyes chemically
      related to ruthenium hexaammine trichloride.
AB  - We tested various cationic dyes chemically related to ruthenium hexaammine
      trichloride (RHT) [i.e., the RHT-cyclohexanedione complex (RHT-CC), pentaamine
      ruthenium N-dimethylphenylenediimine trichloride (PRT), tris-(bipyridyl)ruthenium
      (II) chloride (TRC), tris (bipyridyl) iron (II) chloride (TIC), and cobalt
      hexaammine trichloride (CHT)] for their effectiveness in precipitating cartilage
      matrix proteoglycans in situ. Dyes were introduced into media at the onset of
      processing and were present throughout both aldehyde fixation and osmium
      tetroxide post-fixation. Contrary to expectation, most of the dye-proteoglycan
      complexes generated and stable under aldehyde fixation conditions were found to
      be unstable during post-fixation despite the continuing presence of the dye. A
      similar phenomenon was also found for the cationic dyes commonly used for
      precipitation of proteoglycans in cartilage tissue sections (such as Acridine
      Orange, Alcian Blue, Azure A, Methylene Blue, and Ruthenium Red). Only two dyes,
      i.e., RHT and the newly tested RHT-CC, formed proteoglycan precipitates
      sufficiently stable to resist disruption and extraction during osmium tetroxide
      post-fixation. The latter may be particularly useful in semiquantitative analyses
      of proteoglycan content in unstained tissue sections owing to its intense brown
      black color. For applications in which the osmium tetroxide post-fixation step
      may be omitted, TRC and PRT may also be valuable for semiquantitative
      histochemistry by virtue of their stable fluorescence and intense violet color
      signals, respectively.

PMID- 1376744
TI  - Regulation of rat pulmonary artery endothelial cell transforming growth factor
      beta production by IL-1 beta and tumor necrosis factor-alpha.
AB  - Recent studies suggest that transforming growth factor-beta (TGF-beta) production
      is up-regulated at sites of tissue injury, inflammation and repair, or fibrosis.
      Endothelial cells represent a potentially important in vivo source of TGF-beta;
      however, the identity of endogenous modulators of TGF-beta production by these
      cells remains unclear. To address this issue, the effects of the cytokines, IL-1
      beta, and TNF-alpha on TGF-beta production by rat pulmonary artery endothelial
      cells were examined. Conditioned media from cells treated with 0 to 20 ng/ml IL-1
      beta and/or TNF-alpha were assayed for TGF-beta activity using a mink lung
      epithelial cell line. The results show that rat pulmonary artery endothelial
      cells secreted undetectable amounts of active TGF-beta in the absence of
      cytokines. However, upon acidification of the conditioned media before assay, a
      time-dependent increase in TGF-beta activity was noted in media from both
      untreated and cytokine-treated cells. However, both IL-1 beta and TNF-alpha
      treatment caused the secretion of significantly greater amounts of TGF-beta
      activity than control cells, in a dose-dependent manner, with maximal response
      obtained at cytokine doses of greater than 10 ng/ml. At equivalent doses of
      cytokine tested, the magnitude of the response was significantly greater with IL
      1 beta. These responses were paralleled by increases in steady state mRNA levels
      for TGF-beta 1. Addition of both cytokines resulted in a synergistic response.
      Synergism with IL-1 beta was also noted with the fibrogenic agent bleomycin.
      Kinetic studies indicated that a minimum of 4 h of treatment with either IL-1
      beta or TNF-alpha was required for detection of significant increases in either
      secreted TGF-beta activity or steady state TGF-beta 1 mRNA levels. Thus,
      endothelial cells could play a role in various TGF-beta-dependent processes in
      vivo, in situations wherein IL-1 beta and/or TNF-alpha may be present at
      comparable concentrations.

PMID- 1376745
TI  - Granulocyte colony-stimulating factor (G-CSF) gene transduction in murine
      adenocarcinoma drives neutrophil-mediated tumor inhibition in vivo. Neutrophils
      discriminate between G-CSF-producing and G-CSF-nonproducing tumor cells.
AB  - We have previously demonstrated that the murine colon adenocarcinoma C-26 cell
      line transduced with the human gene for the granulocyte CSF (G-CSF) loses
      tumorigenic activity through a mechanism that involved massive targeting of
      neutrophils at the site of tumor injection. The suppression of tumorigenicity by
      G-CSF was limited to the G-CSF-producing cells and was not transferred to
      nonproducing C-26 cells in a mixed tumor transplantation assay. We present direct
      evidence that neutrophils are involved in this phenomenon. We firstly examined,
      by electron microscopy (EM), the morphology of tumor infiltrates obtained 2, 5,
      and 10 days after s.c. injection of a mixture of G-CSF-producing and 
      nonproducing C-26 cells into syngeneic BALB/c mice. The EM analysis showed at 5,
      but not at 2 or 10 days, the presence of neutrophils in intimate contact with
      tumor cells. We then investigated whether neutrophils discriminate between G-CSF
      producing and -nonproducing C-26 cells. To this aim, C-26 cells were transduced,
      via retroviral vector, with the Escherichia coli LacZ gene and mixed tumor
      transplantation assays were performed by injecting a mixture of G-CSF-producing
      beta-gal- and G-CSF-nonproducing beta-gal+ C-26 cells at different ratios.
      Histologic and EM analysis of the tumors growing at the site of injection were
      carried out. Five days after injection, treatment with x-gal revealed, at the
      histochemical level, the presence of neutrophils around G-CSF producing beta-gal-
      cells; cell-cell contacts and fusion of cell membranes were detected by EM only
      between neutrophils and G-CSF-producing cells. In vitro experiments, performed in
      Boyden chambers, confirmed that the G-CSF produced by C-26 cells was a
      chemoattractant for neutrophils. In addition, a colorimetric, cytostatic assay
      revealed that neutrophils were able to inhibit the growth of G-CSF-producing but
      not of G-CSF-nonproducing C-26 cells. Thus the tumor take after injection of G
      CSF-producing C-26 cells seems to be controlled in situ through two major
      mechanisms namely neutrophil chemotaxis and neutrophil-mediated tumor inhibition.
      The results indicate that neutrophils can discriminate between G-CSF-producing
      and -nonproducing tumor cells and that neutrophils infiltrate the tumor mixture
      as long as G-CSF-producing cells are present.

PMID- 1376746
TI  - A novel IgA receptor expressed on a murine B cell lymphoma.
AB  - The specificity and properties of a novel IgA receptor expressed on the surface
      of a tissue culture-adapted B cell lymphoma, T560, that originated in murine gut
      associated lymphoid tissue, have been explored. Like the IgA receptors of murine
      T and splenic B cells studied by others, the T560 IgA receptor is trypsin
      sensitive and neuraminidase resistant and is up-regulated on T560 cells by
      exposing them overnight to high concentrations of polymeric IgA. Unlike them, the
      T560 IgA receptor is inhibited by low concentrations of IgM and high
      concentrations of IgG2a and IgG2b, binds at pH 4.0 but not at pH 8.0, is down
      regulated by activation of protein kinase C and is sensitive to
      phosphatidylinositol-specific phospholipase C, indicating that it is glycosyl
      phosphatidylinositol-linked to the cell membrane. It is not a cell-bound form of
      galactosyl transferase, does not appear to bind to Ig through carbohydrate
      residues and does not react specifically with antibody to secretory component. It
      may be a completely new, cross-reactive receptor, perhaps related in some way to
      the polymeric Ig receptor or to the receptor for IgA expressed on the apical
      surface of Peyer's patch M cells, which is known to cross-react with IgG.
      Alternatively, it may be homologous to the highly IgA-specific Fc alpha R of T
      cells but, perhaps because of its glycosyl phosphatidylinositol linker, may have
      an ability to move and interact with other Ig receptors on the cell surface such
      that Ig bound to them are cross-inhibitory.

PMID- 1376747
TI  - Mechanisms of lipopolysaccharide-induced neutrophil retention. Relative
      contributions of adhesive and cellular mechanical properties.
AB  - Intravascular LPS rapidly induces neutrophil sequestration in pulmonary
      capillaries by mechanisms that, although currently unknown, must take into
      account the size difference between the neutrophil and capillary diameter. To
      determine whether LPS alters neutrophil stiffness, and hence the ability of
      neutrophils to traverse capillaries, neutrophil passage through pulmonary
      capillaries was modeled by passage through filters with 6.5-microns pores. LPS
      increased retention in the pores in a concentration-dependent fashion that
      required the presence of heat-inactivated platelet-poor plasma, and was evident
      as early as 10 min after stimulation. The effect of LPS on the structural
      properties of the neutrophil was then studied. LPS induced f-actin reorganization
      in neutrophils in the presence of plasma. Disruption of actin organization and
      assembly with cytochalasin D completely inhibited early LPS-induced retention and
      attenuated retention at later timepoints, indicating that LPS-stimulated
      retention depends on filament organization. LPS-induced actin assembly and
      retention were abrogated by an antibody directed against CD14, a putative LPS
      receptor. CD18-dependent adherence of neutrophils contributed significantly to
      retention only at later timepoints with no significant contribution to retention
      at 20 min as determined by inhibition of adherence with the mAb 60.3.
      Morphometric assessment of neutrophil accumulation in the lungs of rabbits given
      1 microgram LPS showed a marked increase in apparent neutrophil number, which was
      unaltered by antibodies to CD18, suggesting that mechanisms other than adhesion
      may account for accumulation in vivo. Direct measurements showed that neutrophil
      stiffness increased with exposure to LPS in a fashion similar to LPS-induced
      retention and actin organization. Pretreatment of neutrophils with cytochalasin D
      attenuated the increased stiffness. These data suggest that reorganization of
      filamentous-actin induced by LPS leads to cell stiffening and retention in
      capillary-sized pores. Although the organization of f-actin continues to be
      important in retention at later time points, adherence of cells also contributes
      significantly to cell retention. The changes in mechanical properties of the
      neutrophil may be important in the sequestration of neutrophils in pulmonary
      capillaries noted in endotoxemia.

PMID- 1376748
TI  - Antigen receptor-mediated protein tyrosine kinase activity is regulated by a
      pertussis toxin-sensitive G protein.
AB  - Ligation of the Ag receptor on B cells is associated with a rapid increase in
      phosphorylation on tyrosine residues of multiple substrates. One of the
      substrates is the phosphoinositide-specific phospholipase C-gamma 1. Because
      activation of phospholipase C-gamma 1 seems to be dependent on tyrosine
      phosphorylation, it is assumed that the two signaling pathways,
      phosphatidylinositol turnover and tyrosine phosphorylation, might be linked.
      However, since the Ag receptor does not possess a kinase domain, it remains
      unclear how these signaling pathways are regulated by the Ag receptor. Previous
      studies have proposed the existence of a receptor-coupled G protein that
      regulates inositol phosphate production in B cells. We confirm that
      phosphoinositide turnover is regulated by a pertussis toxin (PT)-sensitive G
      protein, most probably by controlling phosphorylation of phospholipase C-gamma 1.
      We show that treatment of permeabilized B cells with a nonhydrolyzable GTP
      analogue guanosine 5'-[3-thio]triphosphate induced an increase in tyrosine
      phosphorylation of multiple substrates that are identical to the proteins
      phosphorylated after anti-IgM stimulation. Furthermore, binding of the inactive
      form of G proteins with guanosine 5'-[2-thio]-triphosphate blocked anti-IgM
      induced tyrosine phosphorylation in permeabilized B cells. The results indicate
      that an Ag receptor-coupled G protein controls protein tyrosine kinase activity.
      We show that this G protein is sensitive to PT because tyrosine phosphorylation
      mediated by the Ag receptor was inhibited by this toxin in a concentration
      dependent manner. Similar concentrations of PT also blocked tyrosine
      phosphorylation on phospholipase C-gamma 1 and generation of inositol phosphates.
      Preincubation of intact B cells with PT resulted in inhibition of c-fos mRNA
      expression and DNA synthesis in anti-IgM stimulated B cells, indicating that post
      transcriptional events are also controlled by the Ag-receptor coupled G protein.
      We conclude that Ag receptor-associated protein tyrosine kinase activity is
      regulated by a G protein. This PT-sensitive G protein also regulates
      phosphorylation and activation of phospholipase C-gamma 1 as well as later events
      in B cell activation such as c-fos mRNA expression and proliferation.

PMID- 1376749
TI  - Independent regulation of c-myc, B-myb, and c-myb gene expression by inducers and
      inhibitors of proliferation in human B lymphocytes.
AB  - Although a detailed picture is emerging about the nature of the second messengers
      involved in B cell activation and proliferation, little is yet known about the
      intracellular events taking place further downstream. The c-myb proto-oncogene,
      the structurally related B-myb gene, and c-myc probably code for transcription
      factors, have been demonstrated to be necessary for the proliferation of
      hemopoietic cells, and their expression is indeed induced after mitogenic
      stimulation of T and B lymphocytes. They are therefore likely to be key elements
      in the regulation of gene expression during proliferation. We have set out to
      study the regulation of the expression of these two myb genes and of that of c
      myc in relation to entry into the different phases of the cell cycle during
      mitogenic stimulation of resting human B lymphocytes. Resting tonsillar B cells
      stimulated with the anti-CD20 antibody 1F5 alone are induced to enter the G1 but
      not the S phase of the cell cycle, whereas co-stimulation with the anti-CD40
      antibody G28.5 further drives them to enter the S phase and proliferate. The
      G28.5 antibody alone has been reported to partially activate and increase the
      alertness of resting B cells without inducing them to enter G1. In this report we
      show that increasing the strength of the activating signal leads to progressive
      induction of the proliferation-related genes studied. Thus the G28.5 antibody
      alone induces c-myc mRNA only in resting B cells, 1F5 induces both c-myc and B
      myb, and the full mitogenic signal given by both antibodies together is
      accompanied by increased expression of all three--c-myc, B-myb, and c-myb genes.
      In addition, using a semi-quantitative polymerase chain reaction method, we show
      that different inhibitors of B cell proliferation, namely, cyclosporin A, an anti
      CD19 antibody (HD37), and transforming growth factor beta 1 (TGF-beta 1), inhibit
      differentially the induction of these same genes after mitogenic stimulation of B
      cells. Whereas cyclosporin A inhibits induction of all three genes, TGF-beta 1
      specifically blocks B-myb induction and CD19 has little effect on either of the
      genes tested. We conclude that c-myb, B-myb, and c-myc are regulated
      independently from one another, that induction of c-myc and B-myb together is not
      sufficient to trigger B cell proliferation, and we suggest that expression of all
      three is a prerequisite for proliferation to occur.

PMID- 1376750
TI  - Immunogenetics of collagen-induced arthritis in rats. Both MHC and non-MHC gene
      products determine the epitope specificity of immune response to bovine and chick
      type II collagens.
AB  - Seven inbred, RT1-congenic rat strains were immunized with native bovine (BII),
      porcine (PII), or chick (CII) type II collagen and observed for onset, incidence,
      and severity of arthritis. Clinical results were compared with IgG reactive with
      native rat type II collagen (RII) and the purified, renatured cyanogen-bromide
      peptides of BII, CII, or RII. Immunodominant responses to CB11, CB9,7, and CB12
      of RII were identified. Secondary responses to CB8 and CB10 also occurred.
      Reproducible patterns of peptide reactivity were defined in each strain and
      reflected both RT1 and non-RT1 genotypes plus the species of immunizing collagen.
      BN non-RT1 gene products moderated clinical arthritis but increased the levels of
      reactivity to CB11 in three strains carrying RT1l,n,av1 haplotypes. WF (RT1u)
      rats were susceptible to collagen-induced arthritis (CIA) and developed very high
      levels of autoantibodies with dominant responses to rat CB11 after CII injections
      and to rat CB11 and CB9,7 after BII injections. DA (RT1av1) rats developed the
      most severe arthritis but had only moderate (total) levels of anti-RII IgG: a
      broad response to CB11, CB10, and CB9,7 after CII injections but predominantly to
      CB12 and CB9,7 after BII injections. Three RT1n strains--DA.1N(BN), WF.1N(MAXX),
      and BN--were resistant to BII-induced CIA but developed mild arthritis after
      immunization with CII. After BII: BN IgG reacted with CB9-7, CB11, and CB12;
      DA.1N and WF.1N IgG reacted with CB9,7 and CB12. After CII: BN IgG reacted
      broadly with CB11, CB9-7, CB12, and CB8; WF.1N IgG reacted to CB9-7, CB11, CB8,
      and CB12; DA.1N IgG reacted with CB8, CB11, and CB9-7. Thus, selective induction
      of CIA in BN, WF.1N, and DA.1N rats by CII correlated with serum IgG reactivity
      to rat CB11, but overall strain results identified no single cyanogen-bromide
      peptide as expressing the sole "arthritogenic" epitope in CIA.

PMID- 1376751
TI  - Comparison of the T cell receptors on insulin-specific hybridomas from insulin
      transgenic and nontransgenic mice. Loss of a subpopulation of self-reactive
      clones.
AB  - Transgenic mice expressing the human insulin gene do not produce insulin-specific
      antibody after injection of human insulin. Nevertheless, they have some
      peripheral T cells that proliferate to human insulin in vitro. To investigate the
      nature of these T cells, human insulin-specific T cell hybridomas were produced
      from transgenic and nontransgenic mice. Transgenic hybridomas required more
      insulin to achieve maximum responses and they produced lower levels of
      lymphokines than nontransgenic hybridomas. The majority of nontransgenic
      hybridomas recognized only human and pork insulin whereas transgenic hybridomas
      recognized beef, sheep, and/or horse insulin in addition to human and pork
      insulin. The TCR expressed by transgenic and nontransgenic hybridomas were
      determined by Northern analysis. Both types of hybridomas used several different
      V alpha and V beta gene families and no favored association between V alpha and V
      beta gene usage was detected in either type. V beta 1 was used by 7 of 16
      nontransgenic hybridomas but only by 1 of 16 transgenic hybridomas. V beta 6
      receptors were predominantly expressed by the transgenic hybridomas and all V
      beta 6-bearing hybridomas recognized beef as well as human insulin. The
      differences in Ag reactivity and TCR gene usage suggest that V beta 1-bearing
      human insulin-reactive T cells were clonally deleted or inactivated in the
      transgenic animal. Other clones, representing a minor subpopulation in
      nontransgenic mice, were recovered from transgenic mice.

PMID- 1376753
TI  - Expression of transforming growth factor type beta on human epidermal dendritic
      cells.
AB  - Our study demonstrates that epidermal Langerhans cells (LC) of healthy human skin
      produce Transforming growth factor-beta (TGF-beta). This multipotent mediator
      might keep the immunocompetent LC in an "immature" stage, in which they are able
      to capture and process antigen. Development to potent antigen-presenting cells
      would become possible after migration from the epidermal network to the draining
      lymph node to stimulate (auto-)reactive T-cell clones.

PMID- 1376752
TI  - Signals delivered via MHC class II molecules synergize with signals delivered via
      TCR/CD3 to cause proliferation and cytokine gene expression in T cells.
AB  - We examined the role of MHC class II molecules in transducing signals to
      activated human T cells. Cross-linking of MHC class II molecules synergized with
      submitogenic amounts of anti-CD3 mAb in causing proliferation and secretion of
      the cytokines IL-2, IL-3, IFN-gamma, and TNF-alpha by MHC class II-alloreactive T
      cell lines. Signaling via MHC class II molecules in T cells resulted in
      activation of tyrosine kinases, in generation of inositol phosphates, and in Ca2+
      mobilization that was abrogated by the tyrosine kinase inhibitor herbimycin A.
      Thus, like signaling via TCR/CD3, signaling via MHC class II molecules involved
      tyrosine kinase-dependent activation of phospholipase C, resulting in
      phosphoinositol turnover and Ca2+ flux. However the signaling pathways coupled to
      MHC class II molecules and to TCR/CD3 differed, because engagement of the
      transmembrane phosphatase CD45 inhibited Ca2+ fluxes triggered via TCR/CD3 but
      not Ca2+ fluxes triggered via MHC class II molecules.

PMID- 1376754
TI  - Selective involvement of keratins K1 and K10 in the cytoskeletal abnormality of
      epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma).
AB  - Aggregation of tonofilaments within epidermal keratinocytes is a characteristic
      histologic feature of epidermolytic hyperkeratosis including the generalized form
      known as bullous congenital ichthyosiform erythroderma. The histologic
      distribution and the keratin composition of the altered tonofilaments were
      investigated to determine whether the aggregation was specific to any particular
      keratin(s). Skin samples from seven patients and one mid-trimester fetus with
      generalized epidermolytic hyperkeratosis, and from one patient with a localized
      or "nevoid" form of epidermolytic hyperkeratosis, were analyzed by using various
      microscopical and immunocytochemical methods. A conjunctival sample and cultured
      epidermal keratinocytes from one patient with generalized epidermolytic
      hyperkeratosis were also examined by electron microscopy and immunocytochemistry.
      Ultrastructurally, tonofilament aggregates were distributed within the suprabasal
      stratified epithelial cell layers of the epidermis, of the infundibular part of
      outer root sheaths, and of the sebaceous ducts and sweat ducts, selectively
      following the known distribution pattern of keratins K1 and K10. The abnormal
      tonofilaments were not found in any other cutaneous epithelia, in conjunctival
      epithelium, or in cultured keratinocytes, where K1 and K10 are absent or only
      minimally expressed. Immunoelectron microscopy showed that among the keratins
      detected in suprabasal epidermolytic hyperkeratosis epidermis
      (K1/K5/K10/K14/K16), the aggregated tonofilaments predominantly expressed K1 and
      K10 rather than other keratins. These results suggest that the keratin filament
      abnormality in epidermolytic hyperkeratosis principally involves K1 and K10 and
      raise the question whether epidermolytic hyperkeratosis might be primarily a
      disorder of one or both of these keratins.

PMID- 1376755
TI  - Simple assays of retinoid activity as potential screens for compounds that may be
      useful in treatment of psoriasis.
AB  - Human epidermal cell cultures were used to study the effects of retinoids on
      keratinocyte differentiation. Keratin profiles were studied by quantitative gel
      electrophoresis of culture extracts, whereas the extent of envelope formation was
      assessed in an enzyme-linked immunosorbent assay (ELISA) using an antibody that
      specifically recognizes keratinocyte envelopes. Exposure of cultures to a variety
      of different retinoids produced both dose-dependent decreases in keratin 16 with
      consequent increases in the keratin 14: keratin 16 ratio, and a decrease in
      envelope formation. The order of activity in both assays was similar: arotinoid
      ethyl ester (Ro 13-6298) greater than or equal to arotinoid acid (Ro 13-7410)
      much greater than all trans retinoic acid (Ro 1-5488) greater than acitretin (Ro
      10-1670) greater than or equal to etretinate (Ro 10-9359), the only difference
      being that acitretin was slightly more active than etretinate in the keratin
      assay whereas these retinoids were equi-active in the envelope assay. Analysis of
      the lesional keratins of psoriasis patients showed that etretinate caused a
      reduction in keratin 16 and an increase in the keratin 14:keratin 16 ratio,
      although the magnitude of these changes and their correlation with clinical
      improvement was variable. As the in vitro assays reported here are simple and
      quick, they allow rapid screening of compounds for retinoid-like activity.

PMID- 1376756
TI  - Specificity of antibodies and tuberculin response after occupational exposure to
      tuberculosis.
AB  - Specific antibody levels and delayed-type hypersensitivity skin responses to
      antigens of Mycobacterium tuberculosis in 39 hospital staff who were heavily
      exposed to tuberculosis (TB) were compared with those in 36 factory employees
      from Indonesia. Antibody levels to the TB68 epitope of the 14-kDa antigen were
      significantly greater, while titers to the TB23 (19-kDa) and TB72 (38-kDa)
      epitopes and lipoarabinomannan (LAM) were lower in exposed than in nonexposed
      subjects (all P less than .02). The intensity of tuberculin responses correlated
      positively with anti-LAM and negatively with anti-19-kDa antibody levels.
      Possible reasons for the selective humoral response of chronically exposed
      healthy subjects to the 14-kDa antigen, but not to other antigens immunogenic in
      patients with tuberculosis, are discussed.

PMID- 1376757
TI  - Identification of Toxoplasma gondii bradyzoite-specific monoclonal antibodies.

PMID- 1376758
TI  - Analysis of the Lewisx epitope in human pancreas and pancreatic adenocarcinomas.
AB  - The Lewisx epitope (Gal beta 1-4[Fuc alpha 1-3]GlcNAc-R) can be detected in most
      ductal pancreatic carcinomas. However, few data pertain to its expression in
      normal exocrine pancreas and its biochemistry. We compared the expression of the
      Lewisx epitope in normal pancreas with its expression in pancreatic
      adenocarcinomas and tumor cell lines and to further characterize the nature of
      the antigens bearing this epitope with immunochemical methods. On frozen tissue
      sections of normal pancreas, the Lewisx epitope was detected focally in acinar
      cell granules; sialosyl-Lewisx was detected in centroacinar cells and the
      cytoplasm of intralobular ducts. Sixteen of 19 pancreatic carcinomas expressed
      the Lewisx antigen on tissue sections; however, there was no correlation with
      prognostic parameters, such as tumor grade or stage. Eighteen of 19 tumor
      specimens were positive for sialosyl-Lewisx. Analysis of pancreatic carcinoma
      cell lines (CAPAN-1, CAPAN-2, and DAN-G) revealed intracytoplasmic expression of
      sialosyl-Lewisx epitopes in these cells, and cell surface reactivity was detected
      on flow cytometry for sialosyl-Lewisx. Lectin-affinity chromatography of
      cytoplasmac preparations showed that Lewisx-positive antigens of normal human
      pancreas bind to SBA and UEA-I lectins but have little or no affinity to WGA, GS
      I, or DBA lectins, indicating the presence of Fuc and Gal oligosaccharide
      residues. It was concluded that the Lewisx and sialosyl-Lewisx antigens are
      nonpolymorphic carbohydrate determinants that are present in secretory granules
      of acinar cells, ductules, and pancreatic secretions. This makes the Lewisx
      antigen suitable for the analysis of the secretory process in the exocrine
      pancreas and the study of secretory differentiation antigens in ductal pancreatic
      carcinoma.

PMID- 1376760
TI  - [A case of embryonal carcinoma of the ovary occurred in a 50 year-old woman].

PMID- 1376759
TI  - [Combination chemotherapy with 254-S, ifosfamide and peplomycin for advanced or
      recurrent cervical cancer].
AB  - From favorable results with 254-S, a new cisplatin analogue, single
      administration, we have conducted a clinical study to investigate the efficacy of
      combination of 254-S, ifosfamide and peplomycin, each of which has a different
      dose limiting factor. A total of 45 patients, including 22 patients with stage
      III and IV cervical cancer and 23 cases with recurrent cervical cancer, were
      treated with at least two courses of 254-S (100mg/m2, iv. Day 1), ifosfamide
      (1,500mg/body, iv. Day 1-5) and peplomycin (5mg/body, im. Day 1-6), and tumor
      response was evaluated clinically and by CT scanning. The response rate obtained
      in patients with advanced disease was 81.8% (PR = 17, CR = 1) and that in cases
      with recurrence was 60.9% (PR = 12, CR = 2). Myelosuppression was the dose
      limiting factor. In the 121 courses, grade 3 and 4 of leucopenia and
      thrombocytopenia were observed with an incidence of 44% and 32%, respectively and
      DIC occurred in 3 cases with poor PS though they recovered after reducing the 254
      S dose to 80 mg/m2. The other toxicities were mild except for alopecia.
      Anaphylaxia was observed in a case at the second administration though the
      patient recovered in 15 minutes. There was no death. As to prognosis, a
      significant prolongation of survival period was observed in recurrent cases and 4
      cases are alive (NED) after one and a half year. In the advanced cases, until now
      3 cases of stage IV have died from the disease. We have concluded that this
      regimen is effective as a neoadjuvant chemotherapy for advanced cervical cancer
      and useful for the treatment of recurrent cervical cancer.

PMID- 1376761
TI  - [A study of antenatal screening of congenital anomalies by maternal serum alpha
      fetoprotein].

PMID- 1376763
TI  - [Clinical study of neuropathies].

PMID- 1376762
TI  - [A case of limb body wall complex by prenatally diagnosed maternal serum alpha
      fetoprotein screening].

PMID- 1376764
TI  - [Progress in diagnosis and therapy of hepatitis C].

PMID- 1376765
TI  - Light-activated ion channels in solitary photoreceptors of the scallop Pecten
      irradians.
AB  - Retinas from the scallop Pecten irradians were enzymatically dispersed, yielding
      a large number of isolated photoreceptors suitable for tight-seal recording.
      Whole-cell voltage clamp measurements demonstrated that the phototransducing
      machinery remained intact: quantum bumps could be elicited by dim illumination,
      while brighter flashes produced larger, smooth photocurrents. Single-channel
      currents specifically activated by light were recorded in cell-attached patches,
      and were almost exclusively confined to the rhabdomeric region. Their density is
      sufficiently high to account for the macroscopic photoresponse. Channel
      activation is graded with stimulus intensity in a range comparable to that of the
      whole-cell response, and can be recorded with illumination sufficiently dim to
      evoke only quantum bumps. Light-dependent channel openings are very brief, on
      average 1 ms or less at 20-22 degrees C, apparently not because of blockage by
      extracellular divalent cations. The mean open time does not change substantially
      with stimulus intensity. In particular, since dwell times are in the millisecond
      range even with the dimmest lights, the channel closing rate does not appear to
      be the rate-limiting step for the decay kinetics of discrete waves. The latency
      of the first opening after light onset is inversely related to light intensity,
      and the envelope of channel activity resembles the time course of the whole-cell
      photocurrent. Unitary currents are inward at resting potential, and have a
      reversal voltage similar to that of the macroscopic light response. Voltage
      modulates the activity of light-sensitive channels by increasing the opening rate
      and also by lengthening the mean open times as the patch is depolarized. The
      unitary conductance of the predominant class of events is approximately 48 pS,
      but at least one additional category of smaller-amplitude openings was observed.
      The relative incidence of large and small events does not appear to be related in
      a simple way to the state of adaptation of the cell.

PMID- 1376767
TI  - Influenza virus infection elicits class II major histocompatibility complex
      restricted T cells specific for an epitope identified in the NS1 non-structural
      protein.
AB  - A T cell epitope of the influenza virus NS1 molecule was identified and shown to
      be a determinant used in class II major histocompatibility complex-restricted T
      cell responses to infectious virus. An I-Ed-restricted BALB/c mouse T hybridoma
      clone recognizing influenza virus A/Puerto Rico/8/34 (PR8; subtype H1N1) but not
      A/Udorn/72 (subtype H3N2) secreted lymphokines in response to purified
      recombinant NS1 or fusion proteins containing amino acids 1 to 81 or 1 to 42 of
      NS1. As expected for recognition of a non-virion protein, the clone failed to
      respond to u.v.-inactivated virus. The antigenic determinant was localized by
      synthetic peptides to amino acids 13 to 32 of NS1, explaining the lack of
      recognition of A/Udorn/72 virus which has an alanine to valine substitution at
      position 23 within the determinant. A single intranasal dose of infectious PR8
      virus was found to elicit T cells that responded to peptide NS1 13-32, suggesting
      that this determinant is a significant target of T cells in normal infections. To
      stimulate helper T cell responses similar to those achieved with infectious
      virus, influenza virus vaccines may therefore have to include NS1 in addition to
      virion components.

PMID- 1376766
TI  - Diverse K+ channels in primary human T lymphocytes.
AB  - We used patch clamp techniques to identify and characterize a variety of K+
      channels in primary human peripheral T lymphocytes. The most common channel
      observed in cell-attached configuration was voltage gated and inactivating. In
      ensemble averages, the kinetics of its activation and inactivation were similar
      to those of the whole-cell, voltage-gated K+ current described previously
      (Cahalan, M. D., K. G. Chandy, T. E. DeCoursey, and S. Gupta. 1985. J. Physiol.
      [Lond.]. 358:197-237; Deutsch, C., D. Krause, and S. C. Lee. 1986. J. Physiol.
      [Lond.]. 372:405-423), suggesting that this channel underlies the major portion
      of the outward current in lymphocytes. A small fraction of the time, this or
      another very similar channel was observed to inactivate significantly more
      slowly. Another channel type observed in cell-attached recording was seen less
      frequently and was transient in its appearance. This channel has a unitary
      conductance of approximately 10 pS, similar to the voltage-gated channel, but its
      voltage-independent gating, lack of inactivation, and different kinetic
      parameters showed it to be distinct. In whole-cell recording there is often a
      significant plateau current during sustained depolarization. Experiments using
      whole-cell and excised outside-out configurations indicate that at least part of
      this residual current is carried by K+ and, as opposed to the predominant voltage
      gated current, is charybdotoxin insensitive. These findings are consistent with
      evidence that implicates charybdotoxin-sensitive and -insensitive components in T
      lymphocyte proliferation and volume regulation.

PMID- 1376769
TI  - Antipeptide antisera define neutralizing epitopes on the adenovirus hexon.
AB  - The adenovirus (Ad) hexon contains both group-and type-specific antigenic
      determinants. To identify the latter, peptides were synthesized corresponding to
      residues 281 to 292 from loop 1 and 441 to 455 from loop 2 of the Ad2 hexon.
      These sequences display type-specific variation and have been shown by X-ray
      crystallography to be present on the surface of the virion. Antisera raised
      against the peptides bound both peptide and the native hexon in ELISA, and
      blocked virus infectivity, as determined by immunofluorescence or neutralization
      assays. The loop 1 peptide was shown to inhibit binding of the corresponding
      antiserum to the native hexon in ELISA and to abolish its neutralizing activity.
      Neither the loop 1- nor loop 2-specific antiserum neutralized the infectivity of
      Ad4 or Ad40. Neutralization did not appear to result from aggregation of virus
      particles and thus their inability to attach to the cell, because virions treated
      with immune serum were internalized to the same extent as those treated with
      preimmune serum. Examination of the immune response elicited by Ad2 infection
      revealed that antibodies directed against the L1 and L2 epitopes were also
      present in human serum. Thus, the variable regions exposed on the surface of the
      Ad2 hexon represent type-specific neutralizing antigenic determinants.

PMID- 1376770
TI  - Diversity of the antibody responses produced in ponies and mice against the
      equine influenza A virus H7 haemagglutinin.
AB  - A large panel of mouse monoclonal antibodies was produced and tested against
      field isolates of the equine H7N7 influenza A virus subtype. Only a limited
      degree of H7 haemagglutinin variation was detected. At least four antigenic sites
      were identified by selecting variant viruses in eggs. The limited variation in
      the field did not correlate with the frequency of variant viruses detected in
      eggs; this frequency was similar to those reported for other influenza viruses.
      We sought to determine whether the limited amount of variation could be
      correlated with an epitope-restricted antibody response in vaccinated horses. To
      this end, limiting dilution cultures were established with peripheral blood
      leukocytes from vaccinated ponies and the antibodies released into culture
      supernatants were assayed for binding to variant H7 viruses in ELISA. Three
      neutralizable antigenic sites mapped by mouse antibodies were also recognized by
      antibodies in pony limiting dilution culture supernatants, indicating that the
      equine antibody response against the influenza virus H7 haemagglutinin is
      diverse, and should be effective in selecting variant viruses.

PMID- 1376768
TI  - Distribution of epitopes within the amino acid sequence of the Epstein-Barr virus
      major envelope glycoprotein, gp340, recognized by hyperimmune rabbit sera.
AB  - Epstein-Barr virus (EBV) is a major human pathogen for which the development of
      an effective vaccine remains an important goal. Rabbits were immunized with one
      of a set of 10 fusion proteins representing protein fragments from the EBV
      receptor-binding ligand and candidate subunit vaccine gp340. Sera from recipients
      of fragments from the amino-terminal half of the polypeptide chain bound gp340 in
      Western blot assays and ELISA but were not virus-neutralizing. The fine epitope
      specificity of these sera, and of EBV-neutralizing rabbit sera raised against
      whole EBV and gp340-containing immune-stimulating complexes, were assessed in a
      peptide ELISA. All but two of these sera bound peptides located between positions
      236 and 327 in the 907 amino acids of the gp340 polypeptide chain. Among these it
      was possible to identify regions containing candidate virus-neutralizing B cell
      epitopes. The use of a gp340 fusion protein affinity column to isolate antibodies
      from EBV-neutralizing rabbit sera specific for this region suggests the presence
      of both continuous and discontinuous B cell epitopes with potential roles in EBV
      neutralization.

PMID- 1376771
TI  - Complete replication of a satellite RNA in vitro by a purified RNA-dependent RNA
      polymerase.
AB  - The 334 nucleotide R satellite RNA was used as a template for purified RNA
      dependent RNA polymerase (RdRp) from cucumber mosaic virus-infected tobacco
      plants. The products of the reaction were dsRNA and positive-strand RNA of the
      same size as the R satellite RNA. Similar products were obtained when T7 RNA
      polymerase positive-strand transcripts of a cDNA clone of the satellite RNA,
      designed to have the same 5' and 3' ends as the satellite RNA, were used as
      templates. The formation of the positive strands demonstrates complete
      replication of the satellite RNA. A positive-strand transcript with 65 and 255
      additional nucleotides at the 5' and 3' ends of the satellite RNA respectively
      was also utilized as a template by the RdRp, but only dsRNA was formed. However,
      no products could be detected when the RdRp was programmed with transcripts
      corresponding to the negative-strand satellite RNA, either with no additional
      terminal nucleotides or with 24 and 310 additional nucleotides at the 5' and 3'
      ends respectively.

PMID- 1376772
TI  - Characterization of inner ear sensory hair cells after rapid-freezing and freeze
      substitution.
AB  - In order to determine the ultrastructural organization of normal cells and to
      understand better the anatomical substrates for outer hair cell motility,
      cryofixation was performed on the sensory epithelium of the inner ear of guinea
      pigs prior to substitution of frozen water with organic solvents containing
      chemical fixatives. In this way cells would not be altered by the direct
      application of the chemicals commonly used for preservation, which are also known
      to cause fixation-induced shape changes in outer hair cells. Following rapid
      freezing and freeze-substitution, preservation of cells within the isolated
      sensory epithelium containing the organ of Corti was similar to that seen in
      conventionally fixed cells. However, in rapidly frozen and freeze-substituted
      outer hair cells the cytoplasm and the cellular membranes differed from those
      seen in conventionally fixed preparations. The cytoplasmic matrix was densely
      packed with filaments and stained homogeneously, suggesting better preservation
      of the cytoskeleton and less extraction of the soluble ground substance. Cell
      membranes were smooth, indicating that fixation-induced shape changes and
      shrinkage had been avoided. The subsurface cisternal system of intracellular
      membranes lining the lateral wall of the outer hair cells was composed of
      continuous, tightly packed, parallel rows of membranous lamellae. Thus rapid
      freezing and freeze-substitution are important techniques by which structural
      alterations correlated with outer hair cell motility can be separated from
      fixation-induced cell shape changes.

PMID- 1376773
TI  - Phase I study of taxol and granulocyte colony-stimulating factor in patients with
      refractory ovarian cancer.
AB  - PURPOSE: To increase the taxol dose beyond the current standard dose intensity of
      175 mg/m2 per 21 days in patients with refractory ovarian cancer. PATIENTS AND
      METHODS: Fifteen patients who had platinum-refractory or recurrent advanced-stage
      ovarian cancer were treated with taxol in a phase I trial and were given
      granulocyte-colony stimulating factor (G-CSF). Taxol was administered at doses of
      170, 200, 250, and 300 mg/m2 every 3 weeks. G-CSF was given as a daily
      subcutaneous injection that started 24 hours after the completion of the taxol
      infusion. RESULTS: Four patients required either taxol dose reduction or delay.
      The dose-limiting toxicity (DLT) was peripheral neuropathy, and it occurred at
      300 mg/m2. This toxicity was manifested clinically as a stocking-and-glove
      sensory disturbance that primarily affected proprioception, and was associated
      with objective changes on nerve conduction studies in affected individuals.
      Mucositis was rarely observed. Substantial myelosuppression was observed, but was
      not dose-limiting. Five of 14 assessable patients experienced an objective
      response to therapy, with another five individuals who experienced a 30% to 45%
      reduction in tumor mass. CONCLUSION: Taxol can be safely administered in doses up
      to 250 mg/m2 with G-CSF support, which may make it possible to study taxol dose
      intensification.

PMID- 1376774
TI  - Neurofilament proteins and the mesolimbic dopamine system: common regulation by
      chronic morphine and chronic cocaine in the rat ventral tegmental area.
AB  - The ventral tegmental area (VTA) and its dopaminergic projections appear to
      mediate some of the rewarding properties of opiates, cocaine, and other drugs of
      abuse. In a previous study, we demonstrated that chronic morphine and cocaine
      exert common actions on tyrosine hydroxylase, the rate-limiting enzyme in
      catecholamine biosynthesis, in this dopaminergic brain reward region (Beitner
      Johnson and Nestler, 1991). In the present study, we investigated the effects of
      chronic morphine and cocaine on other phosphoproteins in the VTA by back
      phosphorylation and two-dimensional electrophoretic analysis. It was found that a
      number of phosphoproteins, in addition to tyrosine hydroxylase, were regulated
      similarly by the two drug treatments in this brain region. Several of these
      morphine- and cocaine-regulated phosphoproteins were identified as neurofilament
      (NF) proteins. Chronic, but not acute, administration of either morphine or
      cocaine was found to decrease levels of the three NF proteins, NF-200 (NF-H), NF
      160 (NF-M), and NF-68 (NF-L), by between 15% and 50% in the VTA by back
      phosphorylation, immunolabeling, and Coomassie blue staining. Such regulation of
      NF proteins was selective, in that no detectable changes were observed in the
      levels of eight other major cytoskeletal or cytoskeletal-associated proteins
      analyzed. Furthermore, NF levels were not altered by chronic treatment with
      either imipramine or haloperidol, two psychotropic drugs without reinforcing
      properties, or by chronic stress. Morphine and cocaine regulation of NFs showed
      regional specificity, as NF levels were not altered in the substantia nigra, or
      other parts of the brain or spinal cord, by these drug treatments. NFs are
      thought to function as determinants of neuronal morphology and to be associated
      with axonal transport. Thus, decreased NF levels in the VTA in response to
      chronic morphine and chronic cocaine could lead to drug-induced alterations in
      the structural and functional properties of this brain region, which may
      represent, in turn, part of a common biochemical basis of morphine and cocaine
      addiction and craving.

PMID- 1376775
TI  - SAG: a Schwann cell membrane glycoprotein.
AB  - We report on characterization of a 170,000 Da glycoprotein found exclusively in
      the PNS. We refer to this protein as the Schwann cell membrane glycoprotein
      (SAG). SAG contains the HNK-1 carbohydrate, which is considered by some to be a
      marker of adhesion molecules. Its N-terminal sequence is not similar to
      previously known polypeptide sequences. SAG is found exclusively in the PNS, is
      present in rat sciatic nerve prior to myelination, and is in both myelinating and
      nonmyelinating Schwann cells. Tumors of Schwann cell lineage express SAG where
      axons are present (neurofibromas) but do not in the absence of axons
      (schwannomas). Schwannoma cells in culture do not express SAG even when exposed
      to forskolin, an activator of adenylate cyclase. However, schwannoma cells grown
      in the presence of a neuronal cell line (PC12) express SAG.

PMID- 1376776
TI  - Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5
      tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver
      regeneration and function of hepatic mitochondria in partially hepatectomized
      rats.
AB  - Effects of 1-[(2-Thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5
      tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363), a hepatoprotective
      compound, on liver regeneration, liver nucleic acid levels, mitochondrial
      respiration activity and hepatic energy metabolism after partial hepatectomy
      (OPE) in rats were studied. The liver regeneration rate was significantly
      increased in rats administered 100 mg/kg of KF-14363 for 6 d as compared with the
      control group administered vehicle. The serum glucose level in rats administered
      100 mg/kg of KF-14363 measured 3 h after OPE (OPE 3 h) was significantly higher
      than that in rats administered vehicle (group A) and the serum insulin level in
      the KF-14363 group was more than double that of group A. KF-14363 also
      significantly increased liver nucleic acid levels in OPE rats. In mitochondrial
      function experiments, KF-14363 (100 mg/kg) was orally administered 2 h after OPE.
      Three hours after OPE (1 h after KF-14363 administration), state 3 respiration
      was significantly higher in the OPE 3 h + KF-14363 group than in the OPE 3 h +
      water group. The adenosine diphosphate/oxygen (ADP/O) ratio was also
      significantly higher in the OPE 22 h (22 h after OPE) + KF-14363 group than in
      the OPE 22 h + water group. On hepatic energy metabolism, KF-14363 increased
      adenosine diphosphate and triphosphate levels. Total adenine nucleotide level in
      the OPE 3 h + KF-14363 group was significantly higher than that in the OPE 3 h +
      water group. Adenylate energy charge (AEC) was slightly decreased in the OPE 3 h
      + water group and significantly decreased in the OPE 22 h + water group than in
      the corresponding sham group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376777
TI  - Interaction mode of dicumarol and its derivatives with human serum albumin, alpha
      1-acid glycoprotein and asialo alpha 1-acid glycoprotein.
AB  - The interaction of dicumarol and its seven other derivatives with human serum
      albumin (HSA), alpha 1-acid glycoprotein (AGP) and desialylatedAGP (asialoAGP)
      has been investigated by circular dichroism (CD) and fluorescence. The binding
      parameters of dicumarol and its derivatives obtained from fluorescence almost
      agreed with those obtained from CD. The binding data indicated that the total
      binding affinities (nK) to HSA were higher than the binding affinities to AGP and
      asialoAGP. Hydrophobic interaction was the driving force for the binding to all
      the three proteins and nK values in the binding process were found to be
      increased with the increase of hydrophobicity of the compound. This was evidenced
      by the attempts taken to correlate binding affinities with partition
      coefficients. Both electrostatic and van der Waals interactions were not found to
      play any significant role in the binding of these compounds to any of these three
      proteins. However, in case of the AGP and asialoAGP binding, apart from the
      hydrophobic interaction, some other forces may be involved as evidenced from the
      experimental data. Binding was exothermic, entropy driven and spontaneous. The
      change of enthalpy (delta H degree) was compensated for by the change in entropy
      (delta S degree). Relative contribution of hydrophobic interactions in the
      binding of these compounds to HSA was higher than to AGP or asialoAGP. Sialic
      acid was not found to impart any significant role in the binding of these
      compounds to AGP.

PMID- 1376778
TI  - Inhibition of interleukin-1-alpha-induced nitric oxide synthase in vascular
      smooth muscle and full reversal of interleukin-1-alpha-induced hypotension by N
      omega-amino-L-arginine.
AB  - BACKGROUND: Interleukin-1-alpha (IL-1) is a cytokine with potentially therapeutic
      immunoproliferative and tumoricidal activities. Preliminary clinical studies
      suggest that use of IL-1 may be restricted by dose-limiting hypotension. PURPOSE:
      The purpose of this study was to investigate the role of nitric oxide (NO.) as a
      possible mediator of this hypotension. METHODS: Cytokine-treated rat aortic
      smooth muscle cells were assayed for nitrite production, a stable breakdown
      product of nitric oxide. Nitric oxide synthase from smooth muscle cells was
      partially characterized in cytosol preparations using a novel Fe(2+)-myoglobin
      method to test for nitric oxide production. To determine the role of NO. on the
      immunorestorative and antineoplastic activity of IL-1, N omega-amino-L-arginine
      (NAA) or N omega-monomethyl-L-arginine (NMA), inhibitors of nitric oxide
      synthase, were added to either cultures of IL-1-dependent T cells or A375
      melanoma cells exposed to IL-1. To investigate the effects of NAA in vivo,
      pentobarbital anesthetized dogs, which were made hypotensive by administration of
      IL-1, received a single intravenous bolus dose of NAA. The effects of NAA were
      then reversed by the administration of L-arginine. RESULTS: Our results show that
      cultured IL-1-activated rat aortic smooth muscle cells synthesize nitric oxide, a
      potent vasodilator. Induction of nitric oxide synthase is augmented by interferon
      gamma and blocked by IL-1 receptor antagonist and by inhibitors of RNA or protein
      synthesis. Nitric oxide synthesis by IL-1-activated smooth muscle cells is
      inhibited by NAA, NMA, and N omega-nitro-L-arginine (NNA) with ED50 (i.e.,
      effective dose for 50% inhibition) values of 20, 60, and 1000 microM,
      respectively; this rank order of inhibition is characteristic of an agonist
      unregulated, inducible isoform of nitric oxide synthase. In smooth muscle cells,
      inhibition of NO. synthesis by NAA is reversed by excess L-arginine. Consistent
      with the induction of unregulated NO. synthesis in vascular smooth muscle in
      vivo, administration of IL-1 (50 micrograms/kg) to dogs caused a 33.5% decrease
      in systemic vascular resistance and a 28% decrease in blood pressure within 3
      hours. Subsequent administration of NAA (20 mg/kg) rapidly and completely
      reversed the hypotension and increased systemic vascular resistance; these
      effects of NAA were reversed by L-arginine. Neither the immunoproliferative nor
      the tumoricidal activity of IL-1 was diminished by NAA. CONCLUSIONS: Our results
      indicate that (a) vascular smooth muscle is a likely source as well as a target
      of IL-1-induced NO. synthesis, causing vasodilatation and hypotension, (b) nitric
      oxide synthase inhibitors can fully reverse this hypotension, and (c) the
      therapeutically useful properties of IL-1 are not diminished by nitric oxide
      synthase inhibitors. IMPLICATIONS: Administration of inhibitors of nitric oxide
      synthase can reverse the pathological cardiovascular effects of IL-1 at
      concentrations that do not interfere with the potentially useful
      immunoproliferative or tumoricidal effects of this cytokine. In the context of
      the current clinical trials of IL-1, this finding would represent a very
      significant advantage.

PMID- 1376779
TI  - Leucovorin enhances cytotoxicity of trimetrexate/fluorouracil, but not
      methotrexate/fluorouracil, in CCRF-CEM cells.
AB  - BACKGROUND: Increased response rates in studies of patients with colon cancer
      have indicated that the cytotoxic effects of fluorouracil (5-FU) are potentiated
      by leucovorin (LV) and by methotrexate (MTX). However, preliminary studies using
      a sequential combination of MTX, LV, and 5-FU showed no additional potentiation.
      PURPOSE: We hypothesized that the lack of additional cell kill with this
      combination could be due to competition of LV with MTX for cellular uptake and
      reduced folate polyglutamylation. We have tested this possibility by comparing
      the cytotoxicity of drug combinations containing MTX with that of drug
      combinations containing trimetrexate (TMTX), an antifolate that does not compete
      with LV for uptake or polyglutamylation. METHODS: Human lymphocytic leukemia CCRF
      CEM cells were exposed to MTX or TMTX for 24 hours and to 5-FU during the last 4
      hours of antifolate exposure. LV was administered 30 minutes before 5-FU.
      RESULTS: After 20 hours of exposure to TMTX or MTX, intracellular levels of
      phosphoribosyl pyrophosphate were elevated to a similar degree, and these levels
      did not decrease after a 30-minute exposure to LV. No additional cell kill was
      observed when LV was added to the MTX/5-FU combination, but cytotoxicity was
      enhanced when LV was added to the TMTX/5-FU combination. CONCLUSIONS: This study
      supports the hypothesis that the lack of additional cell kill when high-dose LV
      is added to the MTX/5-FU combination may be due to competition of MTX with LV for
      cellular uptake and/or competition of MTX or its polyglutamates with
      polyglutamylation of reduced folates. Inasmuch as TMTX does not compete with LV
      and reduced folates for uptake and polyglutamylation, the synergy obtained with
      the combination of TMTX plus 5-FU and high-dose LV further supports this
      hypothesis.

PMID- 1376780
TI  - [Intestinal diseases and pathogenic Escherichia coli in early childhood-
      diagnostic methods and their value].
AB  - In the 50th and 60th enteropathogenic Escherichia coli (EPEC) played an important
      role for epidemic diarrhoe in children hospitals and kindergarten. The diagnose
      based on the 0-antigen determination and integration in EPEC-correlated 0-antigen
      groups. We could demonstrate, that 0-antigen identic Escherichia coli strains
      isolated in a short period and a small district are extremely different in
      plasmid profiles. A clonal coherence was not found. 0-antigens are marker of
      Escherichia coli virulence and today EPEC-infections are only sporadic in middle
      Europe. That's why 0-antigen determination is of questionable importance for the
      differentiation of enteropathogenicity. On the other side the role and frequency
      of further intestinal pathogenic Escherichia coli in early childhood is still
      unknown.

PMID- 1376781
TI  - Stuttering and speech naturalness: audio and audiovisual judgments.
AB  - Unsophisticated raters, using 9-point interval scales, judged speech naturalness
      and stuttering severity of recorded stutterer and nonstutterer speech samples.
      Raters judged separately the audio-only and audiovisual presentations of each
      sample. For speech naturalness judgments of stutterer samples, raters invariably
      judged the audiovisual presentation more unnatural than the audio presentation of
      the same sample; but for the nonstutterer samples, there was no difference
      between audio and audiovisual naturalness ratings. Stuttering severity ratings
      did not differ significantly between audio and audiovisual presentations of the
      same samples. Rater reliability, interrater agreement, and intrarater agreement
      for speech naturalness judgments were assessed.

PMID- 1376782
TI  - Effects of intravenous epinine administration on left ventricular systolic
      performance, coronary hemodynamics, and circulating catecholamines in patients
      with heart failure.
AB  - Twenty-six patients with mild to moderate heart failure were studied to determine
      the effects of epinine infusion (at a rate producing plasma levels similar to
      those measured after oral administration of 100 mg of the prodrug ibopamine) on
      left ventricular (LV) function (14 patients), and coronary flow and circulating
      catecholamines (12 patients). The only significant hemodynamic change at an
      infusion rate of 0.5 microgram/kg/min was a 9% (p less than 0.05) decrease in
      systemic vascular resistance (SVR). At an infusion rate of 1 microgram/kg/min
      (mean free epinine plasma levels 14.3 +/- 3.7 ng/ml), heart rate (HR), dP/dtmax
      (1,405 +/- 255 to 1,490 +/- 320 mm Hg, NS), (dP/dt)/DP40, and the relaxation rate
      remained unchanged, but the ejection fraction (EF) increased from 32 to 38% (p
      less than 0.001), cardiac output (CO) increased, and SVR decreased by 22% (p less
      than 0.05). In a separate group of 12 patients, epinine infusion at rates of 0.5
      1 microgram/kg/min produced no significant changes in coronary blood flow or
      myocardial oxygen uptake. At these infusion rates, arterial norepinephrine (NE)
      and dopamine (DA) levels decreased slightly and arterial and coronary sinus
      epinephrine increased. In conclusion, epinine, at concentrations similar to those
      achieved during therapeutic use of ibopamine, had negligible effect on myocardial
      contractility and relaxation rate in heart failure patients. Cardiac pump
      function was improved by a decrease in SVR rather than by inotropic stimulation.
      The data also suggest that these low concentrations of epinine may modulate the
      sympathetic nervous system, but further studies are needed to determine whether
      this effect could have clinical significance.

PMID- 1376784
TI  - Comparison of the effect of renin inhibition and angiotensin-converting enzyme
      inhibition in ovine heart failure.
AB  - The acute hemodynamic and hormonal effects of incremental doses of a specific
      ovine renin inhibitor (RI: EMD 52 297) and captopril were compared in an ovine
      model of heart failure. Both RI and captopril inhibited the renin-angiotensin II
      (ANG II) system, although the decrease in plasma aldosterone (ALDO) was
      significant only during captopril infusion. Both agents exhibited strong
      vasodilator properties with similar decreases in mean arterial pressure (MAP,
      maximum decrease: RI = -20.5 +/- 2.2 mm Hg, p less than 0.001; captopril = -19.8
      +/- 1.7 mm Hg, p less than 0.001) and left atrial pressure (LAP, maximum,
      decrease: RI = -6.8 +/- 1.5 mm Hg, p less than 0.01; captopril = -6.9 +/- 0.4 mm
      Hg, p less than 0.01) along with a slight increase in cardiac output (CO, maximum
      increase: RI = 0.54 +/- 0.11 L/min; captopril = 0.79 +/- 0.26 L/min). The slope
      of the response between MAP and LAP was similar in all animals, indicating that
      the agents have a similar effect on cardiac preload and afterload. The similar
      hemodynamic actions of RI and captopril in this model of congestive heart failure
      suggest that beneficial effects are due to inhibition of ANG II. Thus, orally
      active renin inhibitors may offer a useful therapeutic alternative when side
      effects preclude use of angiotensin-converting enzyme (ACE) inhibitors.

PMID- 1376783
TI  - Renal hemodynamic effects of nonhypotensive doses of angiotensin-converting
      enzyme inhibitors in hypertension and heart failure rats.
AB  - Both circulating and local renin-angiotensin systems (RAS) may contribute to
      cardiovascular homeostasis under normal and pathophysiologic conditions. They may
      also play a role in the effects of angiotensin-converting enzyme (ACE)
      inhibitors. In the present study, we compared systemic and regional hemodynamic
      effects of nonhypotensive doses of captopril and enalaprilate in normal rats,
      spontaneously hypertensive rats (SHR), and rats with heart failure due to
      myocardial infarction (MI). Enalaprilate (0.1 mg/kg) or captopril (3 mg/kg) was
      injected intravenously (i.v.) in conscious rats equipped with miniature Doppler
      flow probes on renal and mesenteric artery and abdominal aorta or an
      electromagnetic flow probe on the ascending aorta to measure cardiac output (CO).
      This resulted in a shift of the angiotensin-I (ANG I) dose-pressor curve (ED50 of
      ANG I after saline 0.21 +/- 0.33 micrograms, enalaprilate 1.45 +/- 0.26
      micrograms, captopril 2.38 +/- 0.73 micrograms; mean +/- SEM; n = 6-12). In the
      systemic hemodynamic groups, no significant changes in mean arterial pressure
      (MAP), CO, or total peripheral resistance (TPR) were observed. In the regional
      hemodynamic groups, enalaprilate caused a slight (-8 +/- 1 mm Hg) reduction in
      MAP in normal rats. Resistance in the hindquarters was not affected by ACE
      inhibitors, whereas only enalaprilate reduced mesenteric resistance in MI rats.
      In contrast, renal resistance was reduced and renal blood flow (RBF) increased
      after captopril in normal and MI rats and after enalaprilate in MI rats. Effects
      were greatest in MI rats (RBF: saline -0.05 +/- 1.9%, enalaprilate 10.3 +/- 2.4%,
      captopril 10.1 +/- 2.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376785
TI  - Regional hemodynamic effects and clearance of endothelin-1 in humans: renal and
      peripheral tissues may contribute to the overall disposal of the peptide.
AB  - We investigated the regional balance of endothelin-1 across the renal and leg
      vascular bed as well as the hemodynamic effects of exogenously administered
      endothelin-1 in six healthy men. Net regional endothelin-1 balance was calculated
      from the respective arteriovenous differences in plasma concentrations and the
      corresponding plasma flow, the latter being determined by para-aminohippurate or
      indocyanine-green dye using appropriate catheter techniques. During constant
      intravenous (i.v.) infusion of endothelin-1 (0.4 pmol/kg/min), a slight increase
      in diastolic blood pressure (p less than 0.05) and a decrease in heart rate (p
      less than 0.01) were observed. In contrast, no significant changes in leg
      hemodynamics were noted. Renal plasma flow decreased by approximately 30%, and
      renal vascular resistance increased by 50% as compared with the control (placebo)
      period (p less than 0.01). Renin plasma concentrations did not change
      substantially during endothelin-1 infusion. During the control (placebo) period,
      arterial endothelin-1 plasma concentrations averaged 2.1 +/- 1.0 pM. An
      equilibrated peptide balance across the leg and a slight renal uptake of
      endothelin-1 was observed. After endothelin-1 infusion, arterial plasma
      concentrations of the peptide increased to 4.9 +/- 1.3 pM (p less than 0.01), and
      a net overall renal and limb uptake of endothelin-1 accounted for approximately 9
      and 6% of the infused endothelin-1 amount, respectively. Results showed that at
      systemic endothelin-1 plasma concentrations, comparable to those which occur in a
      variety of pathologic conditions such as hypertension or cardiogenic shock,
      besides pulmonary clearance, renal and limb uptake of the peptide may also
      contribute to the short half-life (t1/2) of endothelin-1 in humans.

PMID- 1376786
TI  - Cicletanine improves myocardial function deteriorated by ischemia/reperfusion in
      isolated working rat hearts.
AB  - The effect of cicletanine, a novel furopyridine antihypertensive drug was
      compared with that of nitrendipine, a dihydropyridine slow calcium channel
      blocker, on cardiac function and reperfusion-induced ventricular arrhythmias in
      isolated working rat hearts subjected to 10-min ischemia induced by ligation of
      the left main coronary artery followed by 10-min reperfusion. Before ischemia,
      cicletanine and nitrendipine, perfused at concentrations of 3 x 10(-5), 6 x 10(
      5), 10(-4), and 2 x 10(-4) or 10(-8) M, respectively, did not influence heart
      rate (HR), LV developed pressure (LVDP), its first derivative (LVdP/dtmax), and
      LV end-diastolic pressure (LVEDP), whereas aortic flow (AF) was decreased by 2 x
      10(-4) M cicletanine only. Coronary flow (CF) remained unchanged by various
      cicletanine concentrations but was slightly increased by nitrendipine. In the
      concentration range of 3 x 10(-5)-10(-4) M, cicletanine improved AF either in
      ischemia or during reperfusion, whereas 2 x 10(-4) M had no such effect.
      Nitrendipine slightly attenuated ischemia/reperfusion-induced decrease in AF.
      Cicletanine and nitrendipine enhanced LVDP during ischemia. Ischemia-induced
      deterioration of LVdP/dtmax was reduced by cicletanine, during reperfusion, but
      this parameter was reduced by nitrendipine and the highest cicletanine
      concentration. Cicletanine decreased LVEDP significantly during ischemia and
      reperfusion, but nitrendipine had no such effect. All cicletanine concentrations
      reduced the incidence of irreversible ventricular fibrillation (VF) during
      reperfusion, an effect roughly concentration dependent in the range of 3 x 10(-5)
      10(-4) M, whereas nitrendipine had no influence on arrhythmias.

PMID- 1376787
TI  - Residual platelet function under acetylsalicylic acid and the risk of restenosis
      after coronary angioplasty.
AB  - Restenosis after percutaneous transluminal coronary angioplasty (PTCA) was shown
      not to be preventable by antiplatelet therapy; residual platelet function under
      treatment with platelet inhibitors could be one cause of this. Therefore, in a
      prospective investigation, residual platelet function was assessed in 98 patients
      treated with acetylsalicylic acid (ASA) on three occasions during the first 3
      months after successful PTCA. Control cardiac catheterization was obtained in 75
      of these patients (77%) with 82 dilated stenoses 173 +/- 117 days after PTCA.
      Restenosis, defined as diameter stenosis greater than or equal to 50% at control
      angiography, occurred in 41% of the dilated vessels, and 43% of patients
      experienced restenosis in at least one vessel. The in vitro platelet aggregatory
      response to either ADP (0.5, 1, and 10 microM) or collagen (1 and 5 mg/L) as
      aggregating agents did not differ between patients with and without restenosis.
      In addition, neither the collagen-stimulated in vitro synthesis of thromboxane
      nor the basal or prostaglandin E1-stimulated concentrations of cyclic AMP in
      platelet-rich plasma (PRP) was different in the two groups. There was no
      significant correlation between any of the parameters of platelet function
      assessed and the change in coronary luminal diameter observed between immediately
      after PTCA and control coronary angiography. The mean dose of ASA ingested during
      follow-up was also not a determinant of the occurrence of restenosis. Thus,
      residual platelet function under treatment with ASA as measured in vitro in this
      study, did not influence the occurrence of restenosis after successful PTCA.

PMID- 1376788
TI  - Effects of intracoronary administration of endothelin in anesthetized dogs:
      comparison with Bay k 8644 and U 46619.
AB  - The effects of synthetic endothelin on the coronary circulation were studied in
      pentobarbital-anesthetized dogs and compared with those of Bay k 8644, a
      dihydropyridine calcium channel agonist, and U 46619, a thromboxane analogue.
      Intracoronary bolus administration of endothelin reduced coronary blood flow and
      increased coronary arterial resistance. Similarly, intracoronary bolus
      administration of equipotent doses of Bay k 8644 or U 46619 significantly reduced
      coronary blood flow and increased coronary arterial resistance. The coronary
      vasoconstrictor effects of endothelin were long-lasting as compared with the
      transient actions of Bay k 8644 and U 46619. Intracoronary bolus injection of
      endothelin also reduced left ventricular (LV) dP/dt arterial pressure (MAP), and
      cardiac output (CO). In contrast, Bay k 8644 increased LVdP/dt but did not alter
      CO or MAP. Intracoronary bolus injection of U 46619 did not affect MAP, CO, or
      LVdP/dt. In a separate group of animals, intracoronary infusion of nitrendipine
      significantly increased coronary blood flow and reduced coronary arterial
      resistance. Other cardiovascular parameters measured were not significantly
      altered. In the presence of nitrendipine, the effects of intracoronary
      administration of endothelin and U 46619 on coronary blood flow, coronary
      arterial resistance, and LVdP/dt were only partially antagonized. On the other
      hand, the effects of Bay k 8644 were completely prevented in the presence of
      nitrendipine. These studies show that at doses which reduce coronary blood flow
      to the same extent, only endothelin produces myocardial depression in
      anesthetized dogs. The cardiovascular actions of endothelin were only partially
      antagonized by nitrendipine, suggesting that mechanisms other than calcium influx
      through voltage-operated channels are involved.

PMID- 1376789
TI  - Isoproterenol increases defibrillation energy requirements in dogs.
AB  - The effect of intravenous isoproterenol on the energy requirements for successful
      defibrillation (DF) was examined in anesthetized dogs following cholinergic
      blockade with atropine (n = 5) and following treatment with d- and d,l-sotalol (n
      = 16). Defibrillation shocks were administered through left and right ventricular
      epicardial patch electrodes and the energy requirements for DF were studied using
      two different methods. Multiple shocks of varying energies were delivered and the
      energies required for 50% success (E50) and 80% success (E80) in DF were
      estimated using logistic regression. Atropine (0.04 mg/kg) increased E50 by 32 +/
      30% (p = 0.046) and E80 by 39 +/- 38% (p = ns). Subsequent administration of
      isoproterenol (10 micrograms/ml), increasing the heart rate by 52 +/- 35% (p =
      0.025), resulted in a further 108 +/- 21% (p = 0.015) and 88 +/- 55% (p = 0.02)
      rise in E50 and E80 values, respectively. In a second set of experiments, d- (n =
      9) and d,l-sotalol (n = 7) (4 mg/kg bolus followed by 0.025 mg/kg/min maintenance
      infusion) were administered and baseline curves relating delivered energy to %
      success in DF were calculated. Isoproterenol (10 +/- 4 micrograms/min) was given
      to increase the heart rate by 54 +/- 32% (p less than 0.025), and resulted in
      decreases in % success at each of two energy levels, falling in the midrange of
      the dose-response curve. Following d,l-sotalol, % successful shocks fell from 60
      +/- 15 to 42 +/- 28% (p less than 0.05); following d-sotalol, the % success fell
      from 66 +/- 13 to 38 +/- 36% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376790
TI  - Salicylate reduces ventricular dysfunction and arrhythmias during reperfusion in
      isolated rat hearts.
AB  - Recent studies have shown the ability of salicylic acid (SA) to trap hydroxyl
      radicals (OH.) generated during reperfusion in ischemic myocardium. Since OH. is
      implicated in the pathogenesis of reperfusion injury, we examined the effect of
      SA on reperfusion-induced arrhythmias and postischemic ventricular dysfunction.
      Isolated rat hearts perfused by the Langendorff technique were preperfused with
      Krebs-Henseleit buffer containing SA for 10 min. Hearts were then made ischemic
      for 30 min, followed by 30 min of reperfusion. In a separate group, SA was
      administered only at the onset of reperfusion. The left ventricular contractile
      functions, left ventricular developed pressure (LVDP) and its first derivative
      (LV dP/dt), coronary flow (CF), and creatine kinase (CK) release were determined
      before and after ischemia. Epicardial electrocardiogram (ECG) was also recorded
      to analyze the incidence of ventricular tachycardia (VT) and ventricular
      fibrillation (VF). SA improved LVDP, LV dp/dt, and CF recovery and reduced CK
      release compared to the control group. The incidence of VT and VF during
      reperfusion was also significantly reduced by SA. Analysis of tissue
      thiobarbituric acid-reactive products indicates that SA decreased oxidative
      stress during reperfusion. In conclusion, these results suggest that SA reduces
      myocardial reperfusion injury and attenuates ventricular arrhythmias by trapping
      OH. radicals upon reperfusion in isolated rat hearts.

PMID- 1376791
TI  - Class III antiarrhythmic action and inotropy: effects of dofetilide in acute
      ischemic heart failure in dogs.
AB  - We studied the hemodynamic and metabolic effects of the novel class III
      antiarrhythmic agent dofetilide (UK-68,798) in acute ischemic heart failure. In
      pentobarbital-anesthetized dogs, heart failure was induced by microembolization
      of the area supplied by the main left coronary artery until a stable left
      ventricular (LV) end-diastolic pressure of 27 +/- 2 mm Hg was achieved.
      Embolization depressed LV systolic pressure, LV dP/dtmax, LV dP/dtmin, and
      cardiac output. None of these parameters were changed following i.v. infusion of
      dofetilide 5, 10, or 25 micrograms/kg, during spontaneous and paced cycle length
      of 300 ms (n = 9). Heart rate decreased by 12 +/- 8, 19 +/- 7, and 21 +/- 7
      beats/min (p less than 0.05), while QT time increased by 23 +/- 7, 33 +/- 9, and
      40 +/- 10 ms (p less than 0.05) after 5, 10, and 25 micrograms/kg, respectively.
      Ventricular effective refractory period increased from 128 +/- 10 to 153 +/- 11
      ms after 25 micrograms/kg (n = 4). Arterial concentration and net myocardial
      uptake of glucose, lactate, and free fatty acids were not significantly
      influenced by dofetilide. In conclusion, dofetilide, at doses that prolonged
      repolarization, was devoid of cardiodepressive effects in acute ischemic heart
      failure.

PMID- 1376792
TI  - Spare receptors for beta-adrenoceptor-mediated positive inotropic effects of
      catecholamines in the human heart.
AB  - We studied whether the human heart has spare receptors for beta-adrenoceptor
      mediated positive inotropic effects. Thus, we assessed in right atria and left
      papillary muscles of patients with different degrees of heart failure under
      identical experimental conditions affinity (pKI values from (-)
      [125I]iodocyanopindolol binding) and potency (pD2 values from contractile
      responses) for isoprenaline, adrenaline, and noradrenaline in comparison with rat
      heart. Plots of beta-adrenoceptor occupancy versus responses constructed from
      these data revealed that rat left atria and papillary muscles had a large
      receptor reserve for all three beta-adrenoceptor agonists: 50% of maximal
      response was produced with only 1-3% of beta-adrenoceptor occupancy. In human
      heart, however, receptor reserve was considerably lower: 50% of maximal response
      required 8-10% (in right atria) and 20-25% (in left papillary muscles) occupation
      of beta-adrenoceptors. Receptor reserve declined further with an increasing
      degree of heart failure (and decreasing beta-adrenoceptor number): in end-stage
      heart failure (New York Heart Association class IV) both in right atria and left
      papillary muscles a 1:1 ratio between beta-adrenoceptor occupancy and responses
      was observed. These data show that the human heart has only a small receptor
      reserve for beta-adrenoceptor agonists. This may explain why a decrease in beta
      adrenoceptor number leads to a decrease in beta-adrenoceptor function early in
      the development of heart failure.

PMID- 1376794
TI  - Effect of lovastatin on suppression and regression of atherosclerosis in lipid
      fed rabbits.
AB  - The present study was designed to evaluate the effects of lovastatin on
      suppression and regression of atherosclerosis in the lipid-fed rabbit. Fifty
      seven New Zealand rabbits in six groups were fed a 0.3% cholesterol diet for 10
      weeks. In the progression phase of the study, group C10 served as a control and
      received 1 ml of DMSO daily by gavage. Two other groups, L10 and H10, received
      low (L)-dose (10 mg/day) or high (H)-dose (20 mg/day) lovastatin dissolved in 1
      ml of DMSO for 10 weeks. In the regression phase of the study, three groups of
      rabbits received the high lipid diet for 10 weeks and were then shifted to a
      normal diet for the second 10 weeks. During the second 10 weeks, the control
      group C20 received 1 ml of DMSO daily, and groups L20 and H20 received 10 and 20
      mg/day of lovastatin by gavage, respectively. In the progression phase of the
      study, lovastatin significantly attenuated the percent of aortic lesions in
      groups L10 (8 +/- 7%) and H10 (9 +/- 14%) vs. the control group C10 (31 +/- 17%;
      p less than 0.01). There was a similar reduction in pulmonary lesions in groups
      L10 (10 +/- 6%) and H10 (4 +/- 5%) compared to the control group C10 (30 +/- 16%;
      p less than 0.01). There was also a reduction in plaque thickness in both the
      aorta and pulmonary artery, and hence an even greater reduction in estimated
      plaque volume. In the regression phase of the study, lovastatin also
      significantly reduced the percent of aortic lesions (groups L20 and H20 vs. C20:
      27 +/- 18 and 22 +/- 7% vs. 40 +/- 17%; p less than 0.05) and pulmonary lesions
      (21 +/- 10 and 17 +/- 6% vs. 26 +/- 9%; p greater than 0.05 and p less than 0.05,
      respectively); the average maximum plaque thickness of aorta (0.24 and 0.26 mm
      vs. 0.49 mm; p less than 0.01); and the standardized plaque volume per unit area
      of aorta (4.5 and 3.4 vs. 12.1 mm-%; p less than 0.05 and p less than 0.01,
      respectively). However, there was no significant difference in the percent of
      aortic lesions between groups L20 and H20 and group C10 (27 +/- 18 and 22 +/- 7
      vs. 31 +/- 17%; p greater than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1376793
TI  - Aortic baroreceptors exert a tonically active restraining influence on centrally
      mediated depressor responses.
AB  - This study tested the hypothesis that aortic baroreceptors exert a central
      restraining influence on centrally mediated depressor responses and that this
      mechanism is tonically active and is independent of their modulation of basal
      arterial pressure. The effects of short-term (48-72 h) aortic baroreceptor
      deafferentation (ABD) on the acute hemodynamic (peripherally mediated pressor and
      centrally mediated depressor) effects of clonidine were investigated in conscious
      and anesthetized normotensive rats. ABD caused an immediate increase in basal
      arterial pressure and heart rate and a significant attenuation of the
      baroreceptor reflex control of heart rate. Since only arterial pressure subsided
      to control levels by 48-72 h, the data suggest that central reorganizational
      changes were potent enough to overcome the tonically active restraining influence
      of aortic baroreceptors on basal arterial pressure but not heart rate. Clonidine
      produced a similar pressor effect in conscious ABD and sham rats but its
      depressor effect was significantly greater in ABD rats whose baroreceptor reflex
      control of heart rate was significantly attenuated. Intracisternal (i.c.)
      administration of 0.1 microgram of clonidine, a dose that had no effect when
      administered i.v., produced a near-maximal depressor effect in conscious ABD rats
      vs. no effect in sham rats (-16.7 +/- 4.1 vs. -0.3 +/- 2 mm Hg; p less than
      0.001). The depressor effect of clonidine was also enhanced in chloralose
      anesthetized rats and coincided with an anesthesia-induced attenuation of the
      baroreceptor reflex control of heart rate. It is concluded that aortic
      baroreceptors exert a potent restraining influence on the centrally mediated
      depressor effect of clonidine. Since ABD had no significant effect on the
      depressor response to nitroprusside, but enhanced the depressor response to
      ganglion blockade by hexamethonium, the data suggest that a higher peripheral
      sympathetic neural activity existed in ABD rats. The reorganizational changes
      that occurred within 48-72 h after ABD were potent enough to overcome the
      tonically active restraining influence of aortic baroreceptors on basal arterial
      pressure but not on the centrally mediated depressor responses. Thus, the
      buffering influence of aortic baroreceptors and their central projections on
      centrally mediated depressor responses seems to be tonically involved in blood
      pressure control.

PMID- 1376796
TI  - The sinus node inhibitor UL-FS 49 lacks significant inotropic effect.
AB  - UL-FS 49 is a sinus node inhibitor that has been reported to reduce heart rate
      and may be useful in improving myocardial oxygen supply vs. demand. However,
      previous studies performed in a variety of preparations have produced mixed
      results regarding the independent inotropic effect of UL-FS 49. To determine
      whether UL-FS 49 has an inotropic effect, we measured both steady-state
      hemodynamic responses and transient hemodynamic responses to random preload and
      afterload changes, both with and without UL-FS 49. We found that under steady
      state conditions, the effect of UL-FS 49 is so small that it would be of doubtful
      physiologic significance: a 3% increase in stroke volume (p = 0.007) and 7%
      increase in peak positive dP/dt (p = 0.051), in the presence of no statistically
      significant differences in end-diastolic pressure, end-diastolic volume, peak
      systolic pressure, end-systolic pressure, or heart rate. The more powerful
      multiple linear regression modeling of hemodynamic transient sequences resulting
      from random preload and afterload changes showed that UL-FS 49 is without a
      statistically significant direct effect on left ventricular function. We conclude
      that UL-FS 49 has no physiologically important direct effect on left ventricular
      pump function.

PMID- 1376795
TI  - Effects of ibutilide on spontaneous and induced ventricular arrhythmias in 24
      hour canine myocardial infarction: a comparative study with sotalol and
      encainide.
AB  - The electrophysiologic and antiarrhythmic effects of ibutilide, sotalol, and
      encainide were compared in dogs 24 h after myocardial infarction. Ibutilide (0.03
      to 0.3 mg/kg i.v.) prevented the induction of ventricular arrhythmias in 100% of
      the dogs that had demonstrated inducible ventricular arrhythmias prior to
      treatment. This antiarrhythmic action was associated with significant increases
      in ventricular refractoriness and monophasic action potential duration. Sotalol
      (1.0 to 10.0 mg/kg i.v.) increased the ventricular refractory period and
      monophasic action potential duration and prevented the induction of ventricular
      arrhythmias in 75% of the dogs that demonstrated inducible ventricular
      tachyarrhythmias at baseline. Although 10 mg/kg of sotalol was required to
      prevent the initiation of ventricular tachycardia, this dose produced marked
      cardiovascular depression and hypotension in 50% of the dogs tested. Neither
      ibutilide nor sotalol significantly decreased the incidence of spontaneous
      ventricular arrhythmias. The class IC agent encainide (0.3 to 3.0 mg/kg i.v.) was
      successful in preventing the induction of ventricular arrhythmias in only 20% of
      the dogs tested. However, in contrast to ibutilide and sotalol, encainide
      significantly reduced spontaneous arrhythmias. Atrial and ventricular
      refractoriness were significantly increased only after the highest dose of
      encainide tested (3.0 mg/kg). Over the dose ranges studied, the relative efficacy
      for prevention of pacing-induced ventricular arrhythmias was ibutilide greater
      than sotalol much greater than encainide. For suppression of spontaneous
      ventricular arrhythmias, the relative efficacy was encainide much greater than
      ibutilide = sotalol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376797
TI  - Effect of isradipine on cardiopulmonary baroreflex function, regional blood flow,
      and vascular responsiveness in hypertensive patients.
AB  - Calcium channel antagonists, when used to treat hypertension, may modulate
      baroreflex function and vascular responsiveness to endogenous vasoconstrictors.
      We studied regional blood flow, cardiopulmonary baroreflex function, and pressor
      responses in nine hypertensive patients (mean age of 44 +/- 7 years), eight males
      and one female, treated with isradipine (ISR), a dihydropyridine calcium channel
      antagonist, in a placebo-controlled, crossover trial. Each patient underwent
      determination of blood pressure and forearm, splanchnic, and renal blood flows
      (by strain gauge plethysmography and indocyanine green and p-aminohippurate
      clearances, respectively) at baseline and during cardiopulmonary unloading by
      lower body negative pressure (LBNP) at -10 and -20 mm Hg. ISR decreased the mean
      arterial pressure from 105 +/- 2 to 93 +/- 2 mm Hg (p less than 0.01). ISR did
      not change supine forearm or splanchnic vascular resistances, but renal vascular
      resistance fell 30% during treatment (from 0.12 +/- 0.02 to 0.09 +/- 0.01 mm Hg
      min/ml, p less than 0.05). Cardiopulmonary baroreceptor unloading by LBNP
      elicited comparable effects on forearm, splanchnic, and renal vascular resistance
      before and during ISR treatment. Baroreceptor unloading during placebo did not
      change plasma NE or PRA; during ISR, LBNP elicited a progressive rise in these
      hormones. The pressor response to NE was potentiated during ISR treatment (p less
      than 0.05); in contrast, the pressor response to angiotensin II infusion was
      blunted by calcium blockade (p less than 0.05). The present study, therefore,
      demonstrates that calcium channel blockade with ISR preserves, and may even
      augment, cardiopulmonary baroreflex function. These physiologic responses may
      contribute to the relatively low incidence of symptomatic orthostatic hypotension
      observed during chronic treatment with this agent.

PMID- 1376798
TI  - Renal structure and function in rats after suprapharmacologic doses of quinapril,
      an angiotensin-converting enzyme inhibitor.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have adverse effects on renal
      function in some hypertensive patients, and some of them produce renal tubular
      lesions in animals at high doses. To assess the effect of quinapril on renal
      function and structure, a 4-week time-course study was conducted in male Wistar
      rats with daily oral gavage doses of 0, 10, 100, or 400 mg/kg. Glomerular
      filtration rate (GFR) estimated as creatinine clearance and fractional
      electrolyte excretion values were derived from urinalysis and blood chemistry
      data obtained at days 1, 7, 14, and 28. Renal sections were collected on these
      days for histopathologic evaluation, and cortical slices were obtained to assess
      organic ion transport in vitro. Expected pharmacologic effects of an ACE
      inhibitor were observed at all doses and included increased urine output,
      increased water consumption, decreased serum aldosterone (65 or 25% of control at
      10 or 400 mg/kg, respectively, on day 28), increased plasma renin activity (PRA,
      up to two- to threefold higher than controls at day 28), and hypertrophy of the
      juxtaglomerular apparatus. Despite these expected class effects, quinapril
      administration to male rats for 28 days produced no functional alterations or
      renal tubular lesions suggestive of renal toxicity at doses up to 400-fold higher
      than the effective antihypertensive dose in rats.

PMID- 1376799
TI  - Electrophysiologic effects of ambasilide (LU 47110), a novel class III
      antiarrhythmic agent, on the properties of isolated rabbit and canine cardiac
      muscle.
AB  - Electrophysiologic effects of ambasilide in canine isolated cardiac muscle driven
      at 1 Hz and in rabbit sinoatrial (SA) node preparations were determined by
      standard microelectrode technique. Ambasilide (10(-7)-10(-5) M) produced
      concentration-dependent increases in action potential duration measured at -80 mV
      (APD-80) repolarization time in canine ventricular muscle and in Purkinje fibers.
      APD measured at -20 mV (APD-20) was also increased in ventricular muscle, but it
      shortened with 10(-5) M in Purkinje fibers; at this concentration, there was a
      negligible change in the amplitude and the maximum upstroke velocity (Vmax) of
      action potentials and in the resting membrane potential. With the stimulation
      frequency between 30/min and 120/min, ambasilide (10(-5) M) produced a parallel
      increase in APD-80 as well as in APD-20 of ventricular muscle. In Purkinje
      fibers, the prolonging effect of ambasilide on APD-80 was more pronounced at
      lower stimulation frequency, whereas APD-20 shortened at all stimulation
      frequencies. Ambasilide at 10(-5) M also produced a prolongation of the effective
      refractory period (ERP) in Purkinje fibers. The drug produced no significant
      change in the frequency-dependent relationship between ERP and APD-80. A small
      but significant frequency-dependent inhibition of Vmax was noted in both
      ventricular muscle and Purkinje fibers. When the stimulus cycle length was
      reduced from 1,000 to 300 ms, Vmax in ventricular muscle decreased by 8.4 +/-
      3.4% in control solution but by 22.6 +/- 5.6% after 10(-5) M ambasilide (n = 8, p
      less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376800
TI  - Cardiac effects of vecuronium and its interaction with autonomic nervous system
      in isolated perfused canine hearts.
AB  - The chronotropic and inotropic effects of vecuronium bromide and its interaction
      with the autonomic nervous system were investigated in the isolated, cross
      circulated right atrial and left ventricular preparations of the dog. Vecuronium,
      injected into the external jugular vein of the support dog, induced dose
      dependent decreases in heart rate and arterial blood pressure, and increased
      atrial contractile force with no change in sinus rate in isolated atrial
      preparations. Vecuronium (1-3,000 micrograms), injected into the sinus node
      artery of the isolated atrium, induced dose-dependent increases in atrial
      contractile force with small increases in sinus rate. Vecuronium also increased
      the ventricular contractile force in a dose-dependent manner. The positive
      inotropic effect was attenuated in part by propranolol, but not by either
      tetrodotoxin or imipramine. Vecuronium inhibited in a dose-related manner the
      negative chronotropic and inotropic responses to parasympathetic nerve
      stimulation and carbachol (CCh) and the negative followed by positive cardiac
      responses to nicotine, but did not attenuate the positive responses to
      sympathetic nerve stimulation. The ID50s for the responses to parasympathetic
      stimulation, CCh, and nicotine were not significantly different. Vecuronium
      enhanced the positive chronotropic and inotropic responses to sympathetic nerve
      stimulation, tyramine, norepinephrine, and isoproterenol. These results indicate
      that (a) vecuronium causes the positive inotropic responses mediated by
      nonadrenergic mechanisms and beta-adrenoceptors, (b) vecuronium blocks ganglionic
      and presynaptic nicotinic and postsynaptic muscarinic receptor-mediated responses
      similarly, and (c) vecuronium enhances beta-adrenoceptor-mediated responses in
      the dog heart.

PMID- 1376801
TI  - A CNS serotonergic mechanism in acute central hypovolemia in conscious rabbits?
AB  - We tested whether a brainstem serotonergic mechanism influences the hemodynamic
      response to acute central hypovolemia. An inferior vena caval cuff was gradually
      inflated so that mean cardiac index (MCI) fell at a constant rate (approximately
      8%/min). Under control conditions, mean systemic vascular conductance index
      (MSVCI) fell progressively until MCI had fallen by approximately 50%
      (compensatory phase), at which point MSVCI rose abruptly and arterial pressure
      fell to approximately 40 mm Hg (decompensatory phase). Intravenous methysergide
      delayed the decompensatory phase and at a critical dose (300-3,000 nmol)
      abolished it. Methysergide had similar effects when injected into the fourth
      ventricle, pontomedullary cistern, or lateral ventricle in doses that were 7-10%
      of the critical i.v. dose, but had no effect when injected into the spinal
      subarachnoid space. LY53857 was equipotent to methysergide. None of these
      treatments attenuated the vasoconstriction of the first, compensatory, phase.
      Partial depletion of neuronal serotonin (after p-chlorophenylalanine or 5,7
      dihydroxytryptamine treatment) had no effect on either phase. We conclude that a
      serotonergic mechanism, probably located in the brainstem, may be involved in the
      decompensatory phase of acute central hypovolemia.

PMID- 1376802
TI  - Effects of verapamil and Bay K 8644 on defibrillation energy requirements in
      dogs.
AB  - Antiarrhythmic drugs are often required in patients with implantable cardioverter
      defibrillator devices. Prior evidence suggests that drugs modulate defibrillation
      energy requirements by altering ion channel activity. To evaluate the effects of
      calcium ion channel activity on internal defibrillation energy requirements, the
      calcium antagonist verapamil and Bay K 8644, a calcium channel activator, were
      investigated in 30 open-chest, pentobarbital-anesthetized dogs. Defibrillation
      energies were applied across two epicardial patch electrodes. The likelihood of
      successful defibrillation was determined at various shock energy levels, and the
      50 and 90% effective energy doses were calculated using nonlinear regression. In
      saline control experiments (n = 10), the stability of the preparation throughout
      the 6-h duration of the experiments could be demonstrated. Verapamil
      administration (n = 10) infused to a mean plasma concentration of 69 ng/ml
      increased the 50 and 90% effective defibrillation energies by 41 and 43% (p less
      than 0.05), respectively, and to a mean plasma verapamil concentration of 170
      ng/ml by 95 and 75% (p less than 0.01), respectively. The mean cycle length
      during ventricular fibrillation decreased with verapamil and was inversely
      related to the change in defibrillation energy requirement. Administration of Bay
      K 8644 (n = 10) produced a slight increase in the 50% effective defibrillation
      energy (25%; p less than 0.05) and 90% effective defibrillation energy (17%;
      n.s.). The electrophysiologic effects of verapamil were neither prevented nor
      reversed by Bay K 8644. In conclusion, intravenous verapamil administration
      caused an increase in defibrillation energy requirements, but the mechanism by
      which verapamil exerted this effect remains unclear. These experimental data
      suggest that verapamil should be used in patients with automatic implantable
      cardioverter-defibrillator devices only after individual testing.

PMID- 1376803
TI  - Effects of NZ-105, a new calcium antagonist, on renal function in anesthetized
      spontaneously hypertensive rats.
AB  - The effects of a new dihydropyridine derivative, NZ-105, on renal function were
      investigated in anesthetized spontaneously hypertensive rats. Intravenous
      injection of NZ-105 (0.01 and 0.03 mg/kg of body weight) significantly increased
      the urine flow rate (UV) and renal absolute excretion of sodium and chloride.
      Potassium excretion also increased significantly, but it was relatively slight in
      comparison with sodium or chloride excretion. There was a decrease in mean blood
      pressure (-14.5 +/- 2.3 and -22.3 +/- 3.4 mm Hg, 20 min after the administration
      of 0.01 and 0.03 mg/kg of body weight, respectively). The glomerular filtration
      rate (GFR) was not changed; however, the renal plasma flow (RPF) was
      significantly increased. The tubular site of action of NZ-105 was investigated by
      the lithium clearance technique. Intravenous injection of NZ-105 inhibited sodium
      reabsorption beyond the proximal tubules about four to five times more
      effectively than at the proximal tubules. In conclusion, intravenous
      administration of NZ-105 in anesthetized spontaneously hypertensive rats caused
      diuretic and natriuretic action. The possible site of diuretic action may be
      mainly at the nephron segments beyond the proximal tubules.

PMID- 1376804
TI  - Expression of renal alpha 1-adrenergic receptor subtypes in established
      hypertension.
AB  - Radioligand binding studies were undertaken in renal membranes of normotensive
      and hypertensive rats in order to test the hypothesis that there are alterations
      in renal alpha 1-adrenergic subtypes of genetic hypertensive animals. The highly
      selective competitive compound, (+)-niguldipine, was used to distinguish high
      affinity (alpha 1a) from low-affinity (alpha 1b) sites, after initial studies
      demonstrated that this compound had greater selectivity than 5-methylurapidil in
      distinguishing alpha 1a and alpha 1b sites in rat renal membranes. In contrast to
      the significant difference in the blood pressure of the spontaneously
      hypertensive rats (delta BP = 74 mm Hg), there was no difference in the renal
      alpha 1-adrenergic receptor density. Membranes from the whole kidneys of
      spontaneously hypertensive rats (SHRs) possessed 31% alpha 1a and 69% alpha 1b
      sites with -log(Ki) values of 10.0 +/- 0.3 and 7.1 +/- 0.1, respectively, for (+)
      niguldipine. However, these values were not different from those obtained from
      renal membranes of the normotensive Wistar-Kyoto (WKY) rats. These results
      indicate that in spite of the elevated blood pressure during the established
      phase of hypertension, the number, the affinity, and the ratio of the alpha 1a
      and alpha 1b appear not to be responsible for the manifestation of hypertension
      during this phase.

PMID- 1376805
TI  - Differential effects of enalapril and hydralazine on short-term variability of
      blood pressure and heart rate in rats.
AB  - Using a spectral procedure, we studied the acute and chronic effects of enalapril
      and hydralazine on the variability of blood pressure (BP) and heart rate (HR) in
      conscious Wistar rats. In the acute protocol, rats received two injections 25 min
      apart (saline followed by enalaprilic acid or hydralazine hydrochloride). In the
      chronic protocol, animals received oral enalapril maleate, hydralazine
      hydrochloride, or distilled water. A 5-min recording session was initiated on day
      12. Acute enalapril and hydralazine amplified the low-frequency (LF) component of
      the systolic BP (SBP) spectrum. Chronic enalapril reduced the variability of BP,
      as indicated by the lower variance in SBP distribution. Chronic enalapril
      preferentially reduced the amplitude of the 400-mHz oscillations of SBP. Acute
      administration of enalapril or hydralazine resulted in BP variability profiles,
      suggesting a reflexly mediated vascular sympathetic activation. In contrast,
      chronic angiotensin-converting enzyme (ACE) blockade with enalapril caused a
      significant decrease in the LF oscillations of BP. This could reflect a reduced
      sympathetic outflow to vascular smooth muscles.

PMID- 1376806
TI  - Comparison of the safety and efficacy of bisoprolol versus atenolol in stable
      exercise-induced angina pectoris: a Multicenter International Randomized Study of
      Angina Pectoris (MIRSA).
AB  - Bisoprolol 10 mg and atenolol 100 mg once daily were compared regarding efficacy
      and safety in stable effort angina in a 12-week, multicenter, double-blind,
      randomized, parallel-group study. Efficacy was evaluated with angina pectoris
      diaries and bicycle exercise tests. Spontaneously mentioned complaints and side
      effects were recorded at each visit. In 11 centers, 147 patients completed the
      study; 76 received bisoprolol 10 mg, and 71 received atenolol 100 mg. After 12
      weeks, weekly anginal attack rate was reduced significantly (p less than 0.05)
      with bisoprolol (5 +/- 0.5 to 2 +/- 0.6) and with atenolol (4 +/- 0.4 to 1 +/-
      0.2). Peak exercise capacity (in W x min) increased significantly (p less than
      0.05) with bisoprolol (772 +/- 47 to 878 +/- 52) and with atenolol (891 +/- 46 to
      986 +/- 53). Rate pressure product (RPP) at peak exercise (in beats/min x mm Hg)
      decreased significantly (p less than 0.05) with both bisoprolol (25,003 +/- 692
      to 20,116 +/- 637) and atenolol (26,544 +/- 557 to 21,603 +/- 576) (all values
      are mean +/- SE). The differences between the groups were not statistically
      significant. There were no significant differences regarding nature and incidence
      of adverse events between the groups. Thus, bisoprolol 10 mg once daily and
      atenolol 100 mg once daily are equipotent in their effects on stable effort
      angina. Both regimens were comparable with respect to incidence and nature of
      side effects.

PMID- 1376807
TI  - Interaction of atrial natriuretic peptide with DA1 receptors in preconstricted
      isolated perfused rat lungs.
AB  - Using an in situ isolated salt-perfused rat lung preparation, we investigated the
      pulmonary vascular response to atrial natriuretic peptide (ANP). ANP was infused
      in graded doses ranging from 0.01 to 100.0 micrograms/kg during prostaglandin F2
      alpha-induced pulmonary vasoconstriction. These experiments were repeated after
      selective dopamine1 (DA1) receptor blockade with SCH 23390 and after
      catecholamine depletion by reserpine. ANP at doses of 0.01, 0.1, 1.0, 10.0, or
      100.0 micrograms/kg was injected into the pulmonary artery (n = 5-7/dose). In the
      unblocked group ANP infusion resulted in a dose-dependent decrease in the mean
      pulmonary arterial pressure (PAP) with a maximum effect at 10 micrograms/kg
      (delta PAP = -3.4 +/- 0.2 mm Hg). In the DA1 blockade groups the ANP dose
      response curve was shifted to the right, in a parallel fashion. After
      catecholamine depletion with reserpine, the ANP dose-response curve was identical
      to that of the unblocked groups. With the parallel, rightward shift of the ANP
      dose-response curves by SCH 23390 and no attenuation of ANP effect after
      catecholamine depletion, it appears that ANP vasoactive properties in the
      pulmonary vasculature involve an interaction with the vascular DA1 receptors.
      This observation differs from the ANP-dopaminergic interactions seen in the
      kidney in which ANP action depends on endogenous dopamine transmission.

PMID- 1376809
TI  - Effect of E-4031, a class III antiarrhythmic agent, on experimental infarct size
      in a canine model of myocardial ischemia-reperfusion injury.
AB  - Class III antiarrhythmic agents such as E-4031 have demonstrated efficacy in
      preventing and/or terminating malignant ventricular arrhythmias in experimental
      models. It has recently been suggested that Class III agents might possess
      additional antiischemic properties that may translate into a reduction in the
      frequency or severity of arrhythmia. The potential for the Class III
      antiarrhythmic agent E-4031 to limit the extent of developing myocardial
      infarction was assessed in a barbiturate-anesthetized canine model of ischemic
      reperfusion injury. Untreated control (n = 13) and E-4031-treated animals (n = 8,
      300 micrograms/kg, i.v., immediately preceding myocardial ischemia) were
      subjected to a 90-min period of left circumflex coronary artery occlusion
      followed by a 5-h period of reperfusion. The predominant hemodynamic effect
      displayed by E-4031 was a reduction in heart rate throughout the period of
      coronary artery occlusion and early reperfusion. Areas at risk of infarction,
      expressed as percentages of left ventricle, were equivalent in the control and E
      4031 treatment groups (38.5 +/- 1.0 and 34.6 +/- 1.9%, respectively).
      Posterolateral myocardial infarct sizes, expressed either as percentages of risk
      area or of total left ventricle, were reduced slightly but not significantly in
      the E-4031 treatment group compared to the control group (35.2 +/- 5.6 and 45.4
      +/- 3.0% of risk area, respectively; 12.7 +/- 2.4 and 17.6 +/- 1.4% of left
      ventricle, respectively). Regional myocardial blood flows in nonischemic and
      central ischemic zones of myocardium did not differ significantly between the
      control and E-4031 treatment groups before and during the period of coronary
      artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376808
TI  - The effects of cocaine on cardiac electrophysiology in conscious, unsedated dogs.
AB  - This study was performed to determine the cardiac electrophysiological effects of
      cocaine and specifically to determine the time course of these actions. Eighteen
      chronically instrumented conscious dogs were tested with i.v. cocaine at doses of
      1 or 4 mg/kg. The following statistically significant changes were observed 1 min
      following the 4 mg/kg dose of cocaine: heart rate increased from 135 +/- 8 to 186
      +/- 9 beats/min, QRS duration increased from 60 +/- 5 to 74 +/- 5 ms, corrected
      QT interval increased from 298 +/- 7 to 339 +/- 8 ms, intraatrial conduction time
      increased from 27 +/- 2 to 31 +/- 3 ms, atrioventricular conduction time
      increased from 125 +/- 5 to 140 +/- 8 ms, and the atrial effective refractory
      period (ERP) increased from 101 +/- 6 to 130 +/- 9 ms. All of these parameters
      had returned to baseline by 10 min after cocaine administration. Corrected sinus
      node recovery time and the ventricular ERPs were not significantly affected by
      either cocaine dose. The only significant change produced by the 1 mg/kg cocaine
      dose was prolongation of the atrial ERP. These results suggest that cocaine
      causes very transient electrophysiological changes that undoubtedly represent the
      integrated effects of the adrenergic and local anesthetic actions of this drug.

PMID- 1376810
TI  - The inhibition of long-chain fatty acyl-CoA synthetase by enoximone in rat heart
      mitochondria.
AB  - The mechanism by which enoximone, a reported phosphodiesterase inhibitor,
      inhibits the oxidation of long-chain fatty acids was studied in isolated rat
      heart mitochondria using a series of 14C-labeled substrates. Enoximone decreased
      palmitate oxidation in a time- and concentration-dependent manner. Fifty percent
      inhibition of palmitate oxidation was achieved with 250 microM of enoximone. In
      contrast to its effect on palmitate, enoximone (250 microM) increased octanoate
      oxidation by 30%, whereas pyruvate oxidation was unaffected by enoximone. At that
      dose there was no effect on the oxidation of palmitoyl-CoA and palmitoyl
      carnitine. The degree of palmitate oxidation inhibited by enoximone was parallel
      to the inhibition of acyl-CoA synthetase in both rat heart mitochondria and
      microsomes. These results suggest that enoximone is a reversible inhibitor of
      long-chain fatty acyl-CoA synthetase. Moreover, the reaction, which is catalyzed
      by this enzyme, is a rate-limiting step in the pathway of fatty acid oxidation in
      rat heart mitochondria.

PMID- 1376811
TI  - Effects of endothelin-1 on antidiuresis and norepinephrine overflow induced by
      stimulation of renal nerves in anesthetized dogs.
AB  - The effects of endothelin-1 (ET-1) on renal function and norepinephrine (NE)
      overflow induced by renal nerve stimulation (RNS) were examined in anesthetized
      dogs, and comparisons were made with effects of Bay K 8644, a calcium channel
      agonist. RNS at a low frequency (0.5-2.0 Hz) produced significant decreases in
      urine flow and urinary excretion of sodium and increased NE secretion rates
      without influencing renal hemodynamics. RNS, at a high frequency of 2.5-5.0 Hz
      which diminishes renal hemodynamics, affected urine formation and NE secretion
      rate more potently than did low-frequency RNS. Intrarenal arterial infusion of ET
      1 (1.0 ng/kg/min) decreased the baseline level of renal blood flow by 25% and
      that of urinary excretion of sodium by 54-69% but did not alter basal levels of
      NE secretion rate. During ET-1 infusion, low-frequency RNS-induced antidiuresis
      was observed to an extent similar to that seen without ET-1 infusion, whereas
      increase in NE secretion rate elicited by RNS was significantly inhibited by ET-1
      infusion (45-65% of the values without ET-1 infusion). In addition, in the case
      of high-frequency RNS, ET-1 did not affect antidiuretic responses but did inhibit
      the increase in NE secretion rate by approximately 55%. In contrast, alterations
      in renal excretory responses and NE secretion rate elicited by RNS were not
      influenced by Bay K 8644 infusion (1.0 micrograms/kg/min), a dose that decreased
      renal blood flow to the same degree as did 1.0 ng/kg/min of ET-1.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1376813
TI  - Comparative effects of diltiazem, nifedipine, and verapamil on large and small
      coronary artery constriction induced by intracoronary acetylcholine in pigs.
AB  - The in vivo protective effects of diltiazem, nifedipine, and verapamil on large
      and small coronary artery constriction induced by intracoronary injection of
      acetylcholine were compared by coronary arteriography in pigs. The percent
      narrowing of the epicardial major right coronary artery was used as an indicator
      of large coronary artery constriction, and the time required for contrast medium
      to reach the posterior descending coronary artery from the ostium of the right
      coronary artery was used as an indicator of small coronary artery constriction.
      Doses of 12.5, 25, 50, 100, and 200 micrograms of acetylcholine were administered
      into the right coronary artery under left ventricular pacing to keep the systemic
      hemodynamics constant. Marked prolongation of the flow time of contrast medium to
      greater than or equal to 8.1 s (control of less than or equal to 1.8 s) with mild
      narrowing of the epicardial major right coronary artery (less than or equal to
      35%) was observed at doses of 12.5-50 micrograms of acetylcholine and was
      accompanied by myocardial ischemia. Over 50% narrowing of the epicardial major
      coronary artery plus markedly slow flow of contrast medium were induced in 12 of
      the 15 pigs by 100-200 micrograms of acetylcholine. Narrowing of the epicardial
      major coronary artery and the delay time of contrast medium flow induced by
      acetylcholine were both significantly reduced to 12-33% (control: 36-81%) and to
      4.3-16.8 s (control: 16.2-37.7 s) after intracoronary injection of 100 micrograms
      of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376812
TI  - Antihypertensive effect of lisinopril assessed by 24-hour ambulatory monitoring:
      a double-blind, placebo-controlled, cross-over study.
AB  - The antihypertensive effect of the angiotensin-converting enzyme (ACE) inhibitor
      lisinopril administered in a single dose of 20 mg was evaluated by ambulatory
      blood pressure monitoring (ABPM) in a double-blind, placebo-controlled, cross
      over study. Twenty-four patients (21 men and 3 women, mean age 52 +/- 6 years)
      with mild to moderate hypertension were included in the study and randomly
      assigned to two consecutive treatments with lisinopril 20 mg and placebo, each
      administered for 4 weeks. On the last day of each treatment, BP was assessed by
      noninvasive 24-h ABPM. BP was significantly lower after lisinopril than after
      placebo in a 24-h period (mean 24-h systolic BP (SBP) with lisinopril 120 +/- 7
      mm Hg and with placebo 135 +/- 9 mm Hg; mean day SBP with lisinopril 125 +/- 3 mm
      Hg and with placebo 142 +/- 5 mm Hg; mean night SBP with lisinopril 112 +/- 4 mm
      Hg and with placebo 124 +/- 6 mm Hg; mean 24-h diastolic BP (DBP) with lisinopril
      76 +/- 6 mm Hg, and with placebo 87 +/- 8 mm Hg; mean day DBP with lisinopril 80
      +/- 3 mm Hg and with placebo 93 +/- 4 mm Hg; mean night DBP with lisinopril 69 +/
      2 mm Hg and with placebo 79 +/- 5 mm Hg, p less than 0.001). Mean 24-h, mean
      day, and mean night heart rate (HR) did not differ significantly between placebo
      and lisinopril treatments. Repeated-measures analysis of variance (ANOVA) showed
      a significant influence on SBP (p less than 0.001) and DBP (p less than 0.001)
      throughout the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376814
TI  - Chronic arterial vasodilation, central hemodynamics, and cardiac hypertrophy in
      spontaneously hypertensive rats.
AB  - To determine the possible contribution of cardiac volume overload in the failure
      of arterial vasodilators to induce regression of left ventricular hypertrophy
      (LVH), we evaluated in spontaneously hypertensive rats (SHRs) the changes in
      central hemodynamics caused by treatment with hydralazine or minoxidil. Cardiac
      output measured by the thermodilution technique and filling pressures were
      measured in conscious, freely moving rats. Increases in cardiac output were
      observed after 1 day of treatment, and persisted during chronic treatment;
      ganglionic blockade did not affect this increase. However, the LV end-diastolic
      pressure and right atrial pressure of SHRs were not increased by hydralazine or
      minoxidil. Minoxidil increased the LV weight, and decreased the LV wall thickness
      to LV internal radius ratio, whereas hydralazine did not change these parameters.
      We conclude that in SHRs changes in filling pressures do not represent the
      primary stimulus for the persistence or progression of cardiac hypertrophy during
      chronic arterial vasodilation.

PMID- 1376815
TI  - Effects of nisoldipine upon vasoconstrictor responses and binding of endothelin-1
      in ischemic and reperfused rat hearts.
AB  - Changes in the vascular response of isolated, perfused rat hearts to endothelin-1
      (ET-1) and binding of [125I]ET-1 to cardiac membranes were examined following
      ischemia (30 min, zero flow) and reperfusion (15 min). Infusion of ET-1 (0, 2.5,
      5, 7.5, and 10 x 10(-10) M) increased the control heart perfusion pressure (61,
      73, 88, 102, and 117 mm Hg, respectively). Ischemic and reperfused hearts were
      more sensitive to ET-1 infusion (p less than 0.05 at all concentrations).
      Nisoldipine (NIS, 1 nM) prevented the rise in sensitivity to ET-1 following
      ischemia and reperfusion. Two binding sites for [125I]ET-1 were identified in
      cardiac membranes. High-affinity (Kd = 0.04 nM, Bmax = 0.46 pmol/mg of protein)
      and low-affinity (Kd = 13.8 nM, Bmax = 5.4 pmol/mg of protein) sites were
      unchanged by ischemia and reperfusion, and NIS did not change binding constants
      in control or ischemic and reperfused hearts. Increased ET-1 sensitivity after
      ischemia may be due to other factors. Endothelium-dependent vasodilation and
      endothelium-independent vasodilation were significantly reduced following 30 min
      of ischemia. Inhibition of dilator responses may account for increased ET-1
      responses following transient ischemia.

PMID- 1376816
TI  - Differential hemodynamic responses to selective inhibitors of cyclic nucleotide
      phosphodiesterases in conscious rats.
AB  - Selective inhibition of either the low Km cyclic AMP (cAMP) or low Km cyclic GMP
      (cGMP) phosphodiesterase (PDE) promotes vasorelaxation and, consequently,
      produces depressor effects. To evaluate the systemic and regional hemodynamic
      effects of selective inhibitors of these PDE isozymes, CI-930 (0.1-10 mg/kg), an
      inhibitor of low Km cAMP PDE, or zaprinast (3-30 mg/kg), an inhibitor of low Km
      cGMP PDE, was given i.v. to conscious, normotensive rats. The rats were
      chronically instrumented with vascular catheters and either an ultrasonic transit
      time flow probe around the ascending aorta or miniaturized pulsed Doppler flow
      probes around the superior mesenteric and left renal arteries and the abdominal
      aorta. CI-930 and zaprinast, at cumulative doses of 3 and 30 mg/kg, respectively,
      produced comparable reductions in mean arterial pressure (-22 +/- 3 and -19 +/- 4
      mm Hg, respectively) and total peripheral resistance (-0.41 +/- 0.07 and -0.42 +/
      0.06 mm Hg/ml/min, respectively) but affected other hemodynamic variables
      differently. CI-930 at 3 mg/kg increased the heart rate (HR), maximal aortic flow
      acceleration (dF/dt), and peak aortic flow and decreased the stroke volume (SV).
      Cardiac output (CO) was not affected by CI-930. Zaprinast at 30 mg/kg increased
      the CO, dF/dt, and peak aortic blood flow. The HR and SV were unaffected by
      zaprinast. Although both CI-930 and zaprinast increased the dF/dt and peak aortic
      flow, these parameters were affected more by CI-930 than by zaprinast. CI-930
      decreased hindquarter, mesenteric, and renal vascular resistances in a dose
      dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376817
TI  - Central cardiovascular effects of rilmenidine and neuropeptide Y in the conscious
      spontaneously hypertensive rat: haemodynamic and biochemical evidence for a
      negative interaction.
AB  - The possible cardiovascular and biochemical interactions between the imidazoline
      ligand rilmenidine, a novel antihypertensive agent, and neuropeptide Y (NPY) were
      examined in spontaneously hypertensive rats (SHR). Rilmenidine (25-225
      micrograms/kg) and NPY (1.7-15 micrograms/kg) both produced a significant, dose
      dependent reduction in blood pressure (BP) after intracisternal (i.c.)
      administration in conscious SHR. When submaximal doses of rilmenidine (25
      micrograms/kg) and NPY (1.7 micrograms/kg) were coadministered i.c., the
      resultant hypotension and bradycardia was less than either individual response
      and significantly less than the sum of their individual responses, suggesting the
      existence of an inhibitory interaction between these agents. To determine whether
      this interaction was evident at the second-messenger level, the effect of these
      agents on cyclic AMP levels was investigated in slices from the medulla oblongata
      of SHR. NPY (10(-6) and 10(-7) M) significantly inhibited forskolin-stimulated
      cyclic AMP production. Rilmenidine (10(-8)-10(-5) M) itself had no significant
      effect on forskolin-stimulated cyclic AMP levels in this system, but rilmenidine
      (10(-6) M) attenuated the inhibitory effect of NPY (10(-6) M) on cyclic AMP
      production. Thus, an inhibitory interaction between rilmenidine and NPY was
      observed at the hemodynamic and second-messenger level in the SHR.

PMID- 1376818
TI  - Comparative in vitro study of a series of organic nitroesters: unique biphasic
      concentration-effect curves for glyceryl trinitrate in isolated bovine arterial
      smooth muscle and lack of stereoselectivity for some glyceryl trinitrate
      analogues.
AB  - Four different organic nitroesters, constituting a homologous series based on
      unbranched polyalcohols, were compared with regard to in vitro relaxation of
      isolated bovine mesenteric arteries contracted with 2.5 microM phenylephrine. The
      organic nitroesters included ethylene glycol dinitrate (EGDN), dinitratopropane
      (DPN), glyceryl trinitrate (GTN), and tetranitratobutane. Glyceryl trinitrate
      exhibited a biphasic concentration-effect relationship, with pD2 values of 11.5
      +/- 0.5 and 7.2 +/- 0.2 for the high-pD2 and low-pD2 component of the relaxation
      curve, respectively. The high-pD2 and low-pD2 component contributed 28 and 72% of
      the maximal response, respectively. EGDN, DPN, and tetranitratobutane induced
      monophasic concentration-effect curves with pD2 values of 7.4 +/- 0.1, 7.8 +/-
      0.2, and 6.9 +/- 0.6, respectively. Stereoisomeric forms of DPN and
      tetranitratobutane showed no difference with regard to relaxing potency in bovine
      mesenteric artery. GTN has a partly unique mechanism for vascular smooth muscle
      relaxation that distinguishes this compound from other related organic
      nitroesters.

PMID- 1376819
TI  - N-ethylmaleimide diminishes alpha 2-adrenoceptor-mediated effects on
      norepinephrine release in rat tail arteries.
AB  - Isolated tail arteries from Wistar rats, prelabeled with [3H]norepinephrine (NE)
      were subjected to electrical field stimulation (24 pulses at 0.4 Hz and 200 mA).
      Both NE release and vasoconstriction were measured in parallel. The selective
      alpha 2-adrenoceptor agonist B-HT 933 diminished the evoked NE release in a
      concentration-dependent manner. This effect of B-HT 933 was counteracted by the
      selective alpha 2-adrenoceptor antagonist rauwolscine, which given alone enhanced
      evoked transmitter release, indicating the presence of autoinhibition. N
      Ethylmaleimide (NEM) (3 microM), which also in itself increased transmitter
      release, virtually abolished facilitation of release by 0.1 microM rauwolscine
      and diminished its inhibition by 10 microM B-HT 933. The diminution of the
      inhibitory effect of B-HT 933 was even more pronounced when the current strength
      was decreased from 200 mA to 90 mA to compensate for the NEM-induced increase in
      transmitter release. Treatment of the arteries with NEM did not affect the
      perfusion pressure. In contrast, however, the B-HT 933-induced increase in basal
      perfusion pressure was significantly diminished by NEM. Although 10 microM B-HT
      933 given alone did not affect stimulation-evoked vasoconstriction, it caused a
      significant increase in arteries treated with NEM. In conclusion, the observed
      NEM-sensitivity of the presynaptic and vascular alpha 2-adrenoceptor mechanisms
      is compatible with the idea that both pre- and postsynaptic alpha 2-adrenoceptors
      couple to Pertussis toxin (PTX)-sensitive G proteins.

PMID- 1376820
TI  - Effect of the phosphodiesterase inhibitor UK 61260 on human myocardial inotropy
      and diastolic relaxation.
AB  - The phosphodiesterase inhibitor UK 61260 exhibits positive inotropic activity in
      animal studies and is under clinical investigation for treatment of congestive
      heart failure (CHF). We examined the lusitropic and inotropic responses to UK
      61260 in electrically driven (1 Hz, 37 degrees C) human auricular trabeculae
      (AUT, aortocoronary bypass operation, nonfailing hearts, n = 13) and in papillary
      muscle strips (PAP) from moderately (New York Heart Association, NYHA II-III,
      mitral valve replacement, n = 6) and terminally (NYHA IV, heart transplantation,
      n = 7) failing human hearts. For comparison, we studied the effects of UK 61260
      after prestimulation with forskolin (FOR 0.03 microM) and isoprenaline (ISO 0.03
      microM), as well as the effects of milrinone (MIL 1-1,000 microM), ISO (0.01-10
      microM), ouabain (OUA, 0.1 microM), and Ca2+ (1.8-15 mM) in failing human
      myocardium alone. UK 61260 increased force of contraction (FOC), peak rate of
      tension increase (+T) and decay (-T) significantly (p less than 0.01) in AUT but
      not in PAP of NYHA II-III and NYHA IV. Only after prestimulation (FOR and ISO),
      was UK 61260 effective in stimulating FOC in NYHA II-III and NYHA IV. UK 61260
      increased (p less than 0.01) +T and -T, resulting in a shortening of twitch time.
      As judged from the EC50 values, UK 61260 increased FOC more potently than MIL.
      The effectiveness of OUA and Ca2+ in increasing developed tension in human
      failing myocardium was significantly higher as compared with UK 61260. We
      conclude that during stimulation of the cardiac beta-adrenoceptor-adenylate
      cyclase system, UK 61260 increases myocardial systolic and diastolic function in
      failing human myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376821
TI  - Facilitatory role of the renin-angiotensin system in controlling adrenal
      catecholamine release in hemorrhaged dogs.
AB  - Effects of the renin-angiotension system (RAS) on adrenal catecholamine release
      in response to hemorrhagic hypotension and splanchnic nerve stimulation (SNS)
      were studied in pentobarbital-anesthetized dogs. In hemorrhage experiments, mean
      blood pressure (MBP) was maintained at 50 mm Hg for 60 min by bleeding the
      arterial blood into a pressurized bottle. In the renal intact group (control),
      epinephrine (EPI) and norepinephrine (NE) output from the adrenal gland increased
      markedly during hemorrhagic hypotension: from 45 +/- 13 and 4.7 +/- 0.9 to 1,167
      +/- 202 and 169 +/- 30 ng/min at 60 min after onset of hemorrhage, respectively.
      The increases in catecholamine output during hemorrhagic hypotension in the renal
      intact group pretreated with captopril (1 mg/kg intravenously, i.v.) and in the
      renal-ligated group were significantly smaller than those in the control group.
      The increases in catecholamine output in the renal-ligated group infused with
      angiotensin II (AngII 10 ng/kg/min i.v.) were comparable to those in the control
      group. In SNS experiments, AngII infusion (10 ng/kg/min i.v.) enhanced increases
      in catecholamine output induced by 3 Hz SNS significantly. Captopril (1 mg/kg
      i.v.) did not affect the SNS-induced increases in catecholamine output. These
      results suggest that the renal RAS facilitates reflex release of adrenal
      catecholamines during hemorrhagic hypotension, at least in part, by acting
      directly on the release process of catecholamines from dog adrenal gland.

PMID- 1376822
TI  - Evidence for a role of nitric oxide in hypovolemic hemorrhagic shock.
AB  - Hypovolemic hemorrhagic shock was induced in rats by intermittently withdrawing
      blood from an iliac catheter for 20 min until mean arterial blood pressure (MAP)
      decreased to 30 mm Hg. Survival rate, survival time, plasma myocardial depressant
      factor (MDF) activity, MAP, and microscopic gastric alterations were then
      evaluated. NG-nitro-L-arginine methyl-ester (L-NAME), a selective inhibitor of
      nitric oxide (NO) production from L-arginine, was injected intravenously (i.v.)
      after the bleeding was discontinued. Untreated hemorrhagic shocked rats died in
      27 +/- 3.3 min, had enhanced plasma activity of MDF, and exhibited hemorrhagic
      infiltrates in gastric fundus mucosa. L-NAME (5 and 10 mg/kg) significantly
      increased survival rate and time, blunted the increase in plasma MDF activity,
      and protected against the gastric lesions induced by hemorrhagic hypovolemic
      shock. All these protective effects were reversed by a bolus of L-arginine (30
      mg/kg/i.v.), given 2 min after administration of L-NAME. Our findings suggest
      that NO production plays an important role in the pathophysiology of hemorrhagic
      shock.

PMID- 1376823
TI  - Inhibition of granulocyte cAMP-phosphodiesterase by rolipram in vivo is not
      sufficient to protect the canine myocardium from reperfusion injury.
AB  - The purpose of this study was to determine whether the selective type IV cAMP
      phosphodiesterase inhibitor rolipram could reduce the reperfusion injury that
      occurs during myocardial infarction in the anesthetized dog. This question was
      tested in pentobarbital-anesthetized dogs subject to 90 min of regional
      myocardial ischemia and 5 h of reperfusion. Dogs were treated with 1 mg/kg of
      rolipram (i.v., 15 min before reperfusion) followed by a 1 mg/kg/h infusion over
      the duration of the 5 h of reperfusion. Rolipram was tested in vitro for efficacy
      in inhibition of isolated human neutrophil superoxide generation. Rolipram
      produced significant inhibition of superoxide production over the concentration
      range of 0.1-100 microM rolipram when neutrophils were stimulated with a 10(-7) M
      concentration of the chemotactic peptide f-Met-Leu-Phe. Rolipram significantly
      inhibited superoxide generation from human and canine granulocytes in whole blood
      stimulated by zymosan. Therapeutic concentrations of rolipram in the blood of
      dogs were achieved during the course of the experiments with a plasma
      concentration of 0.761 +/- 0.095 micrograms/ml (2.76 +/- 0.34 microM) at the time
      of reperfusion, and 0.574 +/- 0.098 micrograms/ml (2.08 +/- 0.36 microM) at the
      end of the reperfusion period. The relative severity of myocardial ischemia
      between the two treatment groups was similar as assessed with radiolabeled
      microsphere measurement of myocardial blood flow. Transmural myocardial blood
      flows were not significantly different between the two groups after coronary
      occlusion (control, 0.05 +/- 0.01 ml/min/g, n = 6, vs. rolipram, 0.18 +/- 0.07
      ml/min/g, n = 6; p = 0.48).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376825
TI  - Antihypertensive treatment: prevention of cardiovascular disease and prevention
      of events. Satellite symposium to the 5th European Meeting on Hypertension.
      Milan, Italy, June 7-10, 1991.

PMID- 1376824
TI  - Alpha-adrenergic and serotonergic receptors and forearm venous compliance in
      normal human subjects.
AB  - The effect of alpha-adrenergic and serotonergic receptor agonists and antagonists
      on forearm venous capacitance and vascular resistance was studied in normal
      subjects. Venous volumes were significantly decreased by phenylephrine, an alpha
      1-adrenoceptor agonist, and norepinephrine, which stimulates both alpha 1- and
      alpha 2-adrenoceptors, but not by the alpha 2-adrenoceptor agonist clonidine.
      Vascular resistance was increased significantly by all three agonists. Both the
      alpha 2-adrenoceptor antagonist yohimbine and the alpha 1-adrenoceptor antagonist
      prazosin attenuated the venoconstrictor and vasoconstrictor response to
      norepinephrine, indicating that both adrenoceptors are present. 5
      Hydroxytryptamine significantly decreased venous volumes, while vascular
      resistance was not affected. Ketanserin, a 5-HT2 and alpha 1-adrenoceptor
      antagonist, attenuated the venous volume responses to 5-hydroxytryptamine and
      phenylephrine. It is concluded that there are alpha 1- and alpha 2-adrenoceptors
      and 5-HT2 receptors in the forearm venous system. However, vasoactive doses of
      clonidine are not venoconstricting. Forearm veins are sensitive to doses of 5
      hydroxytryptamine, which do not change vascular resistance compared to alpha
      adrenoceptor agonists, which affect both.

PMID- 1376826
TI  - Has antihypertensive treatment prevented vascular disease or vascular events?
AB  - Our current knowledge of the effects of antihypertensive therapy is based on a
      large number of therapeutic trials based on mortal and morbid cardiovascular
      events. Although these events are indeed "hard" data, extrapolations from the
      results of trials based on events cannot be applied to possible effects on the
      underlying cardiovascular disease, particularly coronary artery disease, as the
      mechanisms responsible for the precipitation of events are often different from
      the mechanisms leading to disease. Once a distinction between prevention of
      disease and prevention of events is made, then both must be considered to be
      different, but essential, goals of antihypertensive therapy. The prevention of
      events is a short-term goal for patients who already have disease, and can be
      easily appreciated by traditional event-based trials; the prevention of disease,
      however, is a long-term goal that can be appreciated clinically only after years
      of treatment, but can be assessed within a shorter time frame by measuring plaque
      development, as in new types of randomized trials. Studies of the potential
      actions of antihypertensive drugs on the mechanisms precipitating events,
      particularly thrombotic factors, may further supplement our current knowledge in
      our search for the most appropriate treatment of the hypertensive patient.

PMID- 1376827
TI  - Vascular mechanisms in hypertensive cerebrovascular disease.
AB  - Hypertension causes vascular changes of essentially three types: structurally
      adaptative changes, degenerative alterations unrelated to atherosclerosis, and
      atherosclerosis. Structural changes result in an increased peripheral resistance,
      even in the relaxed vascular bed, and a reduced collateral capacity, thus
      predisposing to ischemia distal to an arterial stenosis/occlusion and to
      "watershed" infarcts in connection with a drop in blood pressure. Degenerative
      changes in the small intracerebral arteries can lead to plasma extravasation and
      focal brain edema, lacunar infarcts, and intracerebral hemorrhages. Hypertension
      also predisposes to saccular aneurysms and subarachnoid hemorrhages. Finally,
      atherosclerotic changes including stenoses or occlusions of predominantly
      extracranial and pial arteries give rise to transitory ischemic attacks and brain
      infarcts by artery-to-artery embolism or distal hemodynamic perfusion
      insufficiency.

PMID- 1376828
TI  - MIDAS: hypertension and atherosclerosis. A trial of the effects of
      antihypertensive drug treatment on atherosclerosis. MIDAS Research Group.
AB  - Although clinical trials of the efficacy of antihypertensive treatment have
      demonstrated impressive reductions in the incidence of stroke, the reduction in
      coronary artery disease mortality has been less impressive. It may be that the
      antihypertensive drugs used in these trials induced metabolic disturbances, or
      produced inadequate regression of left ventricular hypertrophy, thus blunting the
      reduction in risk of coronary artery disease expected with blood pressure
      lowering. Isradipine, a dihydropyridine calcium antagonist known to be an
      effective antihypertensive agent, has also displayed pronounced antiatherogenic
      effects in animals. Thus, a reasonable hypothesis could be that isradipine not
      only reduces the level of blood pressure, but also may have a positive effect on
      the evolution of atherosclerotic plaque in coronary and carotid arteries, thereby
      leading to prevention of clinical sequelae of atherosclerosis. On this basis, a 3
      year clinical trial is being carried out in the United States--the Multicenter
      Isradipine/Diuretic Atherosclerosis Study (MIDAS)--to establish the efficacy of
      isradipine in inhibiting atherogenesis and retarding the progression of
      atherosclerosis in carotid arteries of hypertensive patients. The primary end
      point of the study is intima-media thickness and the extent of atherosclerotic
      plaque in the carotid arteries, as measured by B-mode ultrasonography.

PMID- 1376830
TI  - Platelet activation by low-density lipoprotein and serotonin: effects of calcium
      antagonists.
AB  - Epidemiological studies indicate that there are biological interrelationships
      between blood pressure and blood lipids that may influence the mechanisms whereby
      hypertension is associated with an increased risk of coronary artery disease.
      Serotonin (5-HT) and thromboxane A2, which are released from aggregating
      platelets, mediate platelet-induced vasoconstriction, which itself significantly
      contributes to coronary artery constriction in vivo. Platelet aggregatory
      response to serotonin is modulated by disparate effects of lipoprotein fractions.
      This corresponds to the recognized differences in degree of atherogenicity of low
      (LDL) and high-density lipoprotein (HDL). Amplification of serotonin-induced
      platelet aggregation by LDL and its inhibition by HDL support the hypothesis that
      5-HT-mediated effects represent a mechanism clinically relevant to both chronic
      progression of atherosclerosis (particularly at sites of vascular injury and
      atherosclerotic plaques) and acute thrombotic events. Calcium antagonists differ
      in their platelet-inhibition potency, including their effects on platelet
      response to 5-HT and LDL. Verapamil and isradipine inhibit platelet aggregation
      induced by 5-HT at therapeutic concentrations. Isradipine also inhibits the
      amplifying effect of LDL on 5-HT-induced aggregation. These platelet effects of
      calcium antagonists appear to be neither group- nor class-specific but, rather,
      drug-specific.

PMID- 1376829
TI  - Enhanced risk of thromboembolic disease in hypertension from platelet
      hyperfunction and decreased fibrinolytic activity: has antihypertensive therapy
      any influence?
AB  - Enhanced platelet function and a decrease in fibrinolytic activity have been
      reported in patients with mild hypertension after treatment with various
      nonselective beta-blockers. Until now, such changes have not been reported during
      treatment with beta 1-selective drugs or with agents that have intrinsic
      sympathomimetic activity. The impact of angiotensin-converting enzyme inhibitors
      and diuretics on platelet function and fibrinolytic activity has not been fully
      elucidated. Calcium antagonists of various types, however, are known to decrease
      platelet release in vivo whereas their effects on platelet aggregation and
      fibrinolytic activity are less clear. The new dihydropyridine calcium antagonist
      isradipine, when tested in a group of patients with mild hypertension, resulted
      in a decrease in platelet aggregation, a shortened euglobulin clot-lysis time,
      and a dramatic increase in t-PA (tissue-plasminogen activator) activity after 14
      days of treatment. These changes remained stable throughout the 1-year study
      period. The fact that antihypertensive therapy does not always result in the
      hoped-for prolongation of life, despite satisfactory blood pressure reduction,
      may be in part due to an unfavorable impact on various components of the blood
      clotting system.

PMID- 1376831
TI  - Antiatherosclerotic actions of isradipine.
AB  - Isradipine, a calcium antagonist of the dihydropyridine type, shows
      antiatherosclerotic actions that interfere with all three main mechanisms of
      atherosclerosis. These actions are mediated by the release of prostaglandin I2
      and endothelium-derived relaxing factor, and the subsequent elevation of
      intracellular adenosine-3',5'-cyclic phosphate and 3',5'-guanosine monophosphate,
      respectively. These mechanisms have been proven in vitro and in animal models.
      Preliminary data in humans suggest that these mechanisms have clinical relevance
      in the long-term treatment of patients as well.

PMID- 1376832
TI  - Effects of the calcium antagonist isradipine on 24-hour ambulatory blood
      pressure, platelet aggregation, and neutrophil oxygen free radicals in
      hypertension.
AB  - The effects of isradipine on ambulatory blood pressure, platelet aggregation, and
      oxygen free radicals were assessed in 30 patients with hypertension in a non
      comparative 16-week study. After 4 weeks of placebo run-in, patients received
      isradipine at 2.5 mg twice daily for 12 weeks. The average supine
      systolic/diastolic blood pressure (155 +/- 17/101 +/- 11 mm Hg) was significantly
      reduced at the end of treatment (144 +/- 13/95 +/- 9 mm Hg; p less than 0.01).
      The heart rate was not significantly altered. Isradipine had no adverse effects
      on red or white blood cells or on plasma viscosity. The thromboxane B2 level and
      epinephrine-induced platelet aggregation were significantly (p less than 0.05)
      reduced. High-density lipoprotein cholesterol was significantly (p less than
      0.01) increased after vs. before treatment; total cholesterol was significantly
      (p less than 0.05) increased at midstudy, but this was not significant at the end
      of the study. Other biochemical parameters were unchanged. Studies of neutrophil
      oxygen free radicals by serum opsonized zymosan and phorbol myristate acetate
      were not affected by isradipine. In conclusion, isradipine is an effective
      antihypertensive agent that also has beneficial effects on platelet aggregation
      and lipids while having no effects on neutrophil oxygen free radicals or most of
      the biochemical variables tested, making it an ideal agent for hypertension.

PMID- 1376833
TI  - Tolerability of isradipine in the treatment of mild-to-moderate hypertension in
      general practice: a large-scale surveillance study.
AB  - The tolerability of isradipine was evaluated in an open trial of patients with
      mild-to-moderate essential hypertension as treated in general practice. The
      primary objective was to identify all adverse reactions, especially those that
      were newly occurring (greater than or equal to 6 reports), with a frequency
      greater than 1/1,000. Over 1,100 general practitioners and 5,526 patients
      participated in this trial. After a 2-week washout period, and a 3-week placebo
      run-in, patients with diastolic blood pressure (DBP) greater than or equal to 95
      mm Hg were initially given isradipine at 1.25 mg twice daily. After 4 weeks,
      doses were doubled if DBP was greater than 90 mm Hg. If, after a further 4 weeks
      with doubled dosages, the DBP was still greater than 90 mm Hg, a second
      (nonspecified free-choice) antihypertensive agent was added to the treatment.
      Adverse events were recorded by open questioning. The incidence of adverse events
      was found to be similar to that with placebo; adverse events were generally mild
      or moderate in intensity and disappeared over time. No newly occurring adverse
      events were found. In conclusion, isradipine is safe and well tolerated at
      effective antihypertensive doses in patients with mild-to-moderate hypertension
      as treated in general practice.

PMID- 1376834
TI  - Long-term (2-year) isradipine data in the treatment of mild-to-moderate
      hypertension.
AB  - At the end of a short-term (3-month) study of antihypertensive treatment of mild
      to-moderate hypertension, 141 of the 200 study patients continued into a 2-year
      follow-up of isradipine as monotherapy or in combination with other
      antihypertensive agents. Although all 141 patients completed the first year, only
      102 completed the study. Twenty-four patients dropped out: 2 with flushing; 1
      each with arrhythmia, edema, angina, and headache; 12 who were noncompliant; 2
      with disease unrelated to the study drug; and 4 for reasons unknown. Before the
      follow-up, 70% of the 141 patients were taking isradipine; after 2 years, 63%
      were still taking isradipine as monotherapy. During the follow-up study, the
      blood pressure remained stable (142.9/86.8 mm Hg after 3 months, and 142.9/86.2
      mm Hg after 2 years), whereas the normalization rate was only slightly changed
      (73 vs. 75.2%). The incidence of reported adverse events decreased with time. At
      the end of the short-term study, 44.7% of patients had reported one or more
      adverse events; after 2 years of treatment, only 14.4% reported adverse events.
      Two patients had ECG signs of left ventricular hypertrophy: one showed no
      relevant changes while the other presented clear signs of regression. No
      clinically relevant laboratory abnormalities were noted during the study. In
      conclusion, isradipine is effective, well tolerated and safe in the long-term
      treatment of mild-to-moderate hypertension.

PMID- 1376835
TI  - Isradipine in the treatment of mild-to-moderate hypertension in Portugal.
AB  - A short-term trial of isradipine was conducted to assess its effectiveness and
      tolerability in the treatment of mild-to-moderate hypertension. The study was
      carried out by general practitioners and involved 2,702 patients, aged 18-70
      years, who had diastolic blood pressures (DBP) of 95-114 mm Hg. Patients
      completed a pretreatment phase of up to 4 weeks for antihypertensive drug washout
      and placebo run-in, before entering a 12-week active-treatment phase with 1.25 mg
      of isradipine twice daily, which was increased after 4 weeks to 2.5 mg twice
      daily, depending on the blood pressure response. At the end of 12 weeks, the mean
      systolic blood pressure (SBP) and DBP were 148.1 and 86.7 mm Hg compared with
      169.0 and 103.0 mm Hg after placebo, respectively. The majority of patients
      (89.6%) had a DBP reduction greater than 10 mm Hg, and 86.2% had normalized DBP
      (less than or equal to 90 mm Hg) at the end of treatment. Adverse events were
      reported by 2.8% of patients, and 90% of patients and general practitioners
      reported satisfaction with the treatment. Thus, our results indicate that
      isradipine is effective and well tolerated, and may deserve a place as first-line
      treatment in mild-to-moderate hypertension.

PMID- 1376836
TI  - Clinical efficacy and tolerability of isradipine in the treatment of mild-to
      moderate hypertension in young and elderly patients.
AB  - The clinical efficacy and tolerability of isradipine was evaluated in 63 patients
      with mild-to-moderate hypertension [supine systolic blood pressure (SBP) greater
      than or equal to 160 mm Hg and diastolic blood pressure (DBP) greater than or
      equal to 95 mm Hg]. Patients were divided into two groups according to age: group
      A (n = 41), aged 37-69 years (mean age of 54 +/- 7 years); group B (n = 22), aged
      70-80 years (mean age of 72.8 +/- 2.4 years). After a 3-week washout period,
      group A received 2.5 mg of isradipine twice daily for 6 weeks. Group B received
      1.25 mg of isradipine initially, increasing to 2.5 mg twice daily according to
      treatment response and tolerability. At the end of treatment (week 6), there were
      statistically significant decreases (p less than 0.01) in supine SBP and DBP in
      both groups compared with baseline values: the mean SBP in groups A and B
      decreased from 160.0 +/- 14.7 to 133.6 +/- 10.0 mm Hg and from 161.6 +/- 17.8 to
      134.8 +/- 10.9 mm Hg, respectively; the mean DBP in groups A and B decreased from
      101.3 +/- 3.0 to 83.6 +/- 5.5 mm Hg and from 101.3 +/- 8.4 to 84.2 +/- 3.6 mm Hg,
      respectively. Clinical and laboratory parameters did not change significantly
      during treatment. Side effects (headache, flushing, palpitations, and edema) were
      mild/moderate and disappeared after the first 2 weeks of treatment. In
      conclusion, 2.5 mg of isradipine twice daily is effective and well tolerated in
      the treatment of mild-to-moderate hypertension regardless of patient age.

PMID- 1376837
TI  - Metabolic, hematological, and cardiac effects of long-term isradipine treatment
      in mild-to-moderate essential hypertension.
AB  - Twenty-four patients with mild-to-moderate hypertension (19 women, 5 men; mean
      age of 49 +/- 9.1 years) completed a 2-week washout phase followed by 1 week of
      single-blind placebo. Patients were then given isradipine at 2.5 mg twice daily,
      which was increased to up to 7.5 mg twice daily according to the blood pressure
      response, over a 12-month period. Thirteen patients completed the trial. The
      supine and sitting blood pressure decreased to normal levels within 6 weeks of
      starting active treatment. Heart rate remained unchanged. Plasma cholesterol and
      triglycerides did not change significantly. Plasma high-density lipoprotein (HDL)
      cholesterol increased significantly (p less than 0.05) and a decrease (NS) was
      observed in low-density lipoprotein (LDL) cholesterol and in the LDL/HDL
      cholesterol ratio. Very-low-density lipoprotein (VLDL) cholesterol did not
      change, nor did other biochemical laboratory tests, or electrocardiographic and
      echocardiographic parameters. The most notable side effects were headache (n =
      1), flushing (n = 1), palpitations (n = 3), and pretibial edema (n = 1). In
      conclusion, our results indicate that isradipine is safe and effective in the
      long-term treatment of mild-to-moderate hypertension. It also appears to have
      beneficial effects on lipid metabolism.

PMID- 1376838
TI  - Role of calcium and endothelium in hypertension, cardiovascular disease, and
      subsequent vascular events.
AB  - The response of isolated blood vessels to vasoactive agonists is modulated by
      endothelial cells. Nitric oxide is probably the major endothelium-derived
      relaxing factor (EDRF), although an unidentified hyperpolarizing factor and
      prostacyclin are secreted. Previous studies indicate that the release of EDRF
      must require an increase in cytoplasmic calcium in the endothelial cells. In
      perfused arteries, calcium-channel activators also trigger the release of EDRF;
      thus, the endothelial cell membrane must contain voltage-operated calcium
      channels. However, the increase in cytoplasmic calcium stimulating EDRF release
      is not due to activation of these channels. Endothelial cells also release
      constricting factors (EDCF), most likely superoxide anions, endoperoxides, and
      endothelin. Endothelium-dependent contractions can be evoked by anoxia. These
      contractions, as well as the endothelium-dependent increases in tension evoked by
      stretch in cerebral arteries, are inhibited by calcium antagonists. This
      inhibitory effect is at the level of vascular smooth muscle, not the endothelium.
      Thus, calcium antagonists do not prevent the release of either EDRF or EDCF.
      Indeed, by facilitating the inhibition exerted by the former and preventing the
      activation of vascular smooth muscle by the latter, they favor dilation.

PMID- 1376839
TI  - Clinical equivalence of once-daily administration of a modified-release
      formulation of isradipine and twice-daily administration of the standard
      formulation. Multicentre Study Group.
AB  - In a double-blind, parallel-group comparative study, once-daily administration of
      a modified-release formulation of isradipine (Im, n = 189) was compared with
      twice-daily administration of the standard formulation (Is, n = 191). Following a
      3- to 5-week placebo period, patients with a sitting diastolic blood pressure
      (sDBP) of greater than or equal to 100 mm Hg but less than or equal to 120 mm Hg
      were randomized to receive either Im at 5 mg once daily or Is at 2.5 mg twice
      daily for 6 weeks. A double-dummy technique was used to maintain blindness and no
      dosage titration was made. Blood pressure was always recorded in the morning
      before drug administration (12 h after the previous administration of Is or 24 h
      after the previous administration of Im). The mean sDBP was reduced significantly
      (p less than 0.001) and equally in both groups, and the normalization rate (sDBP
      less than or equal to 90 mm Hg) was 54% with Im and 55% with Is. Adverse events
      were slightly less frequent overall in the patients receiving Im than Is (23 vs.
      28%, respectively) as was the incidence of typical dihydropyridine side effects
      such as flushing and headache. The results show that once-daily administration of
      5 mg of Im is as effective and better tolerated than 2.5 mg twice daily of Is
      while providing adequate blood pressure control at the end of the 24-h dosing
      interval.

PMID- 1376840
TI  - Postexercise reflex control of forearm vascular resistance during calcium
      antagonism with slow-release oral isradipine.
AB  - In untreated hypertensive patients, blood pressure is decreased during the hours
      that follow a single bout of exercise, but the mechanisms involved are as yet
      unknown. As antihypertensive chemotherapy may interfere with cardiovascular
      regulation, we investigated the effects of calcium antagonism with isradipine
      (slow-release oral formulation, SRO) on postexercise blood pressure and on the
      reflex control of forearm vascular resistance in patients with mild-to-moderate
      hypertension. The results show that isradipine SRO exerted an additional blood
      pressure-lowering effect after exercise that was associated with a further
      decrease in forearm vascular resistance. The reflex changes in forearm vascular
      resistance were potentiated after exercise, but were not further affected by
      isradipine SRO. Therefore, isradipine SRO does not interfere with the
      cardiovascular mechanisms that act to decrease blood pressure after exercise in
      patients who have hypertension.

PMID- 1376841
TI  - Pharmacological modulation of stress-induced cardiovascular hyperreactivity in
      essential hypertension.
AB  - The effects of the calcium antagonist isradipine and the beta-blocker metoprolol,
      which are based on different antihypertensive therapeutic principles, were
      evaluated in 52 men with mild-to-moderate hypertension in a 6-week, double-blind,
      randomized study. Mental stress-testing was performed before and after active
      treatment. With isradipine (n = 26), the stress-induced responses of cardiac
      output and total peripheral resistance were not significantly changed, but the
      blood pressure (BP) response, specifically the diastolic response, was decreased.
      With metoprolol (n = 26), there was a decreased response of cardiac output and an
      increased response of total peripheral resistance, and the BP response was even
      greater than it had been before treatment. Thus, these results indicate that beta
      blockade is effective in reducing cardiac responsiveness but, because of vascular
      counterregulatory mechanisms, BP responsiveness is not decreased. In contrast,
      calcium antagonism preserves the physiological hemodynamic profile while reducing
      BP responsiveness to stress.

PMID- 1376842
TI  - Does isradipine exert a special early-morning blood pressure-lowering effect?
AB  - The blood pressure-lowering effect of isradipine at 1.25-2.5 mg twice daily
      (taken at 0700 and 1900 h) was assessed in a double-blind study involving 28 men
      with mild-to-moderate hypertension. After a 4-week placebo period, patients were
      randomized to receive either isradipine (group I) or placebo (group II) for 8
      weeks. At the end of the placebo and active-treatment periods, patients were
      evaluated by 24-h ambulatory blood pressure monitoring. Data were analyzed
      according to two time periods: daytime, 1000-2300 h; nighttime and early morning,
      2300-1000 h. Intersubject analyses were performed comparing values at the end of
      placebo with those at the end of active treatment. Intrasubject two-way analysis
      of variance showed that the time of day or night had no influence on blood
      pressure changes. Comparison of systolic (SBP) and diastolic (DBP) blood
      pressures with isradipine indicated that there were significantly greater average
      decreases in SBP at 0600-0800 h than at 1800-2000 h (p = 0.038), and at 0800-1100
      h than at 2000-2300 h (p = 0.045). This was also true for the average decreases
      in DBP (p = 0.006). In conclusion, isradipine exerts blood pressure control
      throughout 24 h with a pronounced action during the early morning (0600-0800 h)
      period.

PMID- 1376843
TI  - Isradipine in the treatment of hypertensive crisis in ambulatory patients.
AB  - In order to investigate the efficacy of isradipine in the treatment of
      hypertensive crisis, we treated three groups of patients who had diastolic blood
      pressure (DBP) greater than 120 mm Hg, and who were without signs of acute target
      organ damage. Isradipine was given sublingually in doses of 1.25 mg (group 1; n =
      10), 2.5 mg (group 2; n = 10), and 5 mg (group 3; n = 7). Mean arterial pressure
      (MAP) was reduced in all patients [from 153.4 +/- 4.3 to 124.0 +/- 2.3 mm Hg at
      60 min, and to 118.0 +/- 2.1 mm Hg at 2 h after administration (p less than
      0.001)]. The heart rate (HR) did not change significantly (from 82.4 +/- 3.7 to
      84.0 +/- 6 beats/min; NS). No significant differences were noted in the overall
      responses of the three groups; however, blood pressure reduction was more rapid
      in the group receiving 5 mg compared with the other two dosages. These results
      show that isradipine given sublingually is effective in reducing the elevated
      blood pressure of a hypertensive crisis and is not accompanied by limiting side
      effects. Isradipine's onset of action is early (approximately 30 min after
      dosing) and reaches its maximum blood pressure response within 2 h of
      administration. No dose-dependent reductions in blood pressure were observed with
      the dosage range employed in this study.

PMID- 1376844
TI  - Regression of cardiac hypertrophy in hypertensive patients by long-term treatment
      with isradipine.
AB  - The aim of this study was to assess the effects of long-term (9-month) treatment
      with isradipine, alone or combined with bopindolol, on blood pressure, left
      ventricular hypertrophy (LVH), and diastolic function. Thirty-five hypertensive
      patients with LVH and supine diastolic blood pressures (DBPs) greater than or
      equal to 100 and less than or equal to 120 mm Hg received increasing doses of
      isradipine (1.25, 2.5, and 5 mg twice daily); if blood pressure was not
      controlled, bopindolol (0.5-2 mg once daily) was added to the treatment. Clinical
      and laboratory investigations were carried out after placebo for baseline values,
      and after 5 and 9 months of isradipine treatment alone (n = 11) or combined with
      bopindolol (n = 24). At the end of the study, blood pressure was significantly
      decreased while heart rate did not change with isradipine alone, but decreased
      significantly after the addition of bopindolol. Although the DBP was normalized
      (less than or equal to 90 mm Hg) in 28 patients (80%), complete reversal of the
      left ventricular mass index (LVMI) was seen in only 7 patients (20%). The ratio
      of early to atrial filling did not change, but the deceleration time was
      significantly decreased after 9 months. No laboratory abnormalities or important
      side effects were observed. Although isradipine alone or combined with bopindolol
      was effective in controlling blood pressure and significantly reduced the LVMI
      after 5 months, improvement in diastolic function was seen only after 9 months of
      active treatment.

PMID- 1376846
TI  - Effects of isradipine on hypertension and renal hemodynamics.
AB  - The safety and efficacy of isradipine as well as its long-term effects on renal
      hemodynamics were evaluated in a study of 17 patients with mild-to-moderate
      essential hypertension and normal or slightly impaired renal function. After a 4
      week placebo period, isradipine was administered according to a schedule of
      increasing dosages ranging from 1.25 to 5 mg twice daily. During treatment and at
      the latest follow-up (at 6 months), isradipine was found to lower blood pressure
      (diastolic and systolic) significantly. There were no significant side effects or
      changes in blood chemistry during treatment. Plasma renin activity and serum
      aldosterone were slightly raised whereas the glomerular filtration rate, renal
      plasma flow, and filtration fraction were significantly raised at the latest
      follow-up compared with the pretreatment levels.

PMID- 1376845
TI  - Hemodynamic effects of isradipine and nifedipine in chronic sustained
      hypertension.
AB  - As isradipine is known to be less cardiodepressant than nifedipine, myocardial
      wall stress--an important determinant of cardiac oxygen demand--may also be more
      favorably influenced by isradipine. Therefore, the acute effects of an
      intravenous (i.v.) infusion of isradipine (0.4 mg) vs. nifedipine (2.0 mg) on
      cardiac hemodynamics and systolic wall stress were investigated in a crossover
      study of 12 hypertensive patients. Vasodilation-induced reflex activation was
      limited by pretreatment with i.v. propranolol at 0.1 mg/kg of body weight. The
      hemodynamic parameters measured were statistically comparable at baseline and
      after propranolol with both calcium antagonists, as was blood pressure reduction.
      However, the end-systolic volume decreased with isradipine, but not with
      nifedipine [before: 69 +/- 7.0 ml (mean +/- SEM); after: 61 +/- 6.1 ml; 2p less
      than 0.01 vs. before: 62 +/- 6.1 ml; after: 64 +/- 7.0 ml; NS, (difference
      between changes in response to treatments: 2p less than 0.05)]. The ejection
      fraction increased only with isradipine vs. nifedipine [before: 48 +/- 2.3%;
      after: 54 +/- 2.3%; 2p less than 0.001 vs. before: 52 +/- 2.0%; after: 52 +/-
      2.3%; NS (difference between changes in response to treatments: 2p less than
      0.05)]. Systolic wall stress decreased significantly more with isradipine than
      with nifedipine [before: 2,767 +/- 231; after: 2,153 +/- 162 relative units; 2p
      less than 0.001 vs. before: 2,636 +/- 212; after: 2,310 +/- 199 relative units;
      2p less than 0.05 (difference between changes in response to treatments: 2p less
      than 0.05)]. These results suggest that isradipine, given acutely, unloads the
      heart more than does nifedipine.

PMID- 1376847
TI  - Effects of long-term administration of isradipine on renal hemodynamics and
      sodium metabolism.
AB  - The objective of this double-blind, placebo-controlled study was to evaluate the
      effects of isradipine on renal hemodynamics and function. Ten patients with mild
      to-moderate hypertension were given isradipine at 2.5 mg twice daily for 3 months
      after 4 weeks of placebo washout. Renal studies were performed 2 h after the
      morning administration of treatment. The results of these evaluations indicate
      that isradipine as monotherapy significantly reduced the mean arterial pressure,
      while the effective renal plasma flow was increased (+16%) and glomerular
      filtration rate remained virtually unchanged (-8.7 ml/min). The filtration
      fraction and renal vascular resistance decreased significantly. There was a
      significant decrease in the absolute rate of proximal sodium reabsorption, and a
      significant increase in the distal reabsorption. Clearance of sodium remained
      unchanged. In conclusion, monotherapy with low-dose isradipine was not only
      effective in controlling blood pressure, but also decreased the renal vascular
      resistance while avoiding glomerular hyperfiltration, and exerted a protective
      effect on renal hemodynamics. Natriuresis also remained stable despite the blood
      pressure reduction.

PMID- 1376849
TI  - Cardiovascular diseases, blood rheology, and dihydropyridine calcium antagonists.
AB  - Over the last 10 years, accumulating evidence has confirmed the ability of
      dihydropyridine calcium antagonists to improve red blood cell deformability. In
      this review of the literature, particular attention is paid to results obtained
      with isradipine, a second-generation derivative of the 1,4-dihydropyridine
      family. Isradipine appears to be more selective in various pharmacological
      properties, well tolerated, easy to administer, and effective in controlling
      blood pressure and reducing the frequency of ischemic events. While manifesting
      these desirable attributes, isradipine retains an unimpaired ability to improve
      red blood cell deformability. It is suggested that the therapeutic efficacy of
      dihydropyridine calcium antagonists is attributable, at least in part, to their
      ability to affect blood rheology by improving red blood cell deformability.

PMID- 1376848
TI  - Long-term antihypertensive and renal effects of isradipine in hypertensive
      patients with normal and reduced renal function.
AB  - The long-term hemodynamic and antihypertensive effects of isradipine were
      investigated in 11 patients who had normal renal function and 9 who had reduced
      renal function. The dose regimen was 1.25-5 mg twice daily, depending on blood
      pressure response. After 24 weeks of active treatment, systolic/diastolic blood
      pressure decreased from 172/106 to 155/94 mm Hg (p less than 0.05) in the
      patients with normal renal function, and from 176/105 to 169/93 mm Hg (p less
      than 0.01) in those with impaired renal function. Contrary to the results of
      short-term treatment, no changes in inulin and p-aminohippuric acid (PAH)
      clearances were observed in either study group. There were no significant changes
      in plasma renin, aldosterone, glucose, or lipids, nor were these changes in
      protein excretion in either group; however, sodium excretion increased
      significantly in both groups. On the basis of our results, we conclude that
      isradipine has a place in the treatment of hypertensive patients with mild renal
      insufficiency.

PMID- 1376850
TI  - Effect of isradipine on responses to standardized physical stress tests in
      hypertension of pregnancy.
AB  - Fourteen women with hypertension of pregnancy and who were in their last
      trimester were subjected to three standardized physical stress tests before and
      after 1-2 weeks of treatment with 5 mg of isradipine twice daily. Their blood
      pressure and heart rate responses to the isometric handgrip exercise, the cold
      pressor test, and the orthostatic tilt test were recorded. Treatment with
      isradipine reduced systolic and diastolic blood pressures significantly at rest.
      However, although the diastolic blood pressure was reduced during the stress
      tests, the decrease was significant only during cold pressor testing.

PMID- 1376851
TI  - Donor dendritic cells after liver and heart allotransplantation under short-term
      immunosuppression.

PMID- 1376852
TI  - Haemolytic uraemic syndrome during FK506 therapy.

PMID- 1376853
TI  - Use of teaching methods within the lecture format.
AB  - A survey was carried out at Dorset House School of Occupational Therapy, Oxford,
      into the perceived effectiveness of different teaching methods used within the
      lecture format in the Human Biology Courses for Year 1 and Year 2. Results showed
      that the traditional, didactic lecture was perceived by the students as the least
      effective method used, yet by involving the students actively within the lecture
      time the format was enhanced and was regarded as a more effective
      teaching/learning tool. Experimental tasks and learning packages used within the
      lecture format were also perceived by the students as effective. Some trends were
      noted relating to the age of students and the different perceptions of
      effectiveness of teaching methods. The implication of these results on the
      planning and financing of courses is discussed.

PMID- 1376854
TI  - The use of the liquid crystal display (LCD) panel as a teaching aid in medical
      lectures.
AB  - The liquid crystal display (LCD) panel is designed to project on-screen
      information of a microcomputer onto a larger screen with the aid of a standard
      overhead projector, so that large audiences may view on-screen information
      without having to crowd around the TV monitor. As little has been written about
      its use as a visual aid in medical teaching, the present report documents its use
      in a series of pathology lectures delivered, over a 2-year period, to two classes
      of about 150 medical students each. Some advantages of the LCD panel over the
      35mm slide include the flexibility of last-minute text changes and less lead time
      needed for text preparation. It eliminates the problems of messy last-minute
      changes in, and improves legibility of, handwritten overhead projector
      transparencies. The disadvantages of using an LCD panel include the relatively
      bulky equipment which may pose transport problems, image clarity that is inferior
      to the 35mm slide, and equipment costs.

PMID- 1376855
TI  - Simultaneously occurring alopecia areata and Hodgkin's lymphoma: complete
      remission of both diseases with MOPP/ABV chemotherapy.
AB  - A 43-year-old man presented with simultaneously occurring alopecia areata and
      stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's
      disease were present for 6 months, and rapidly developing patchy hair loss of the
      scalp was present for 2 weeks prior to presentation. The patient was treated with
      eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of
      Hodgkin's-disease. Four months after the completion of chemotherapy, the patient
      had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may
      be an autoimmune disease and may respond to chemotherapy.

PMID- 1376857
TI  - Cell biology. Devious devices of Salmonella.

PMID- 1376856
TI  - CNQX binding to non-NMDA glutamate receptors in canine cerebro-cortical crude
      synaptosomal membranes: pharmacological characterization and comparison of
      binding parameters in dogs with congenital portosystemic encephalopathy and
      control dogs.
AB  - The pharmacological profile and binding characteristics of the non-NMDA
      antagonist of glutamate receptors [3H]6-cyano-7-nitro-quinoxaline-2,3-dione
      (CNQX), were investigated in triton-washed crude synaptosomal membranes prepared
      from canine cerebral cortex. [3H]CNQX binding was inhibited by various glutamate
      agonists and antagonists, the rank order of potency being CNQX greater than alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) = quisqualate = kainate
      greater than glutamate. Two binding sites for [3H]CNQX were apparent when non
      specific binding (NSB) was defined with unlabelled CNQX. In contrast, when NSB
      was defined with saturating concentrations of unlabelled AMPA and kainate, only
      one binding site was identified which corresponded to the high affinity site
      identified when CNQX was used to define NSB. No physiologically relevant
      differences were found in binding parameters for [3H]CNQX membranes from dogs
      with congenital portosystemic encephalopathy (PSE) when compared with control
      dogs. The affinity constant (Ki) of AMPA displacement of [3H]CNQX binding was not
      significantly different in PSE dogs compared with control dogs. These results
      suggest that the antagonist site on cortical non-NMDA receptors is not perturbed
      in dogs with congenital PSE.

PMID- 1376859
TI  - Cranial metastasis of hepatocellular carcinoma associated with chronic epidural
      hematoma--case report.
AB  - A case of cranial metastasis of hepatocellular carcinoma associated with epidural
      hematoma in a 58-year-old male is presented. The epidural hematoma demonstrated
      an unusual chronic clinical course and computed tomographic appearance.
      Associated bleeding from either the diploic marrow or emissary veins might be a
      cause of the slowly expanding hematoma, and the outward displacement of the
      artificial bone-flap implanted previously may also have contributed to the
      chronic course.

PMID- 1376858
TI  - [Therapeutic potentials of cytokines and growth factors in severe infections].

PMID- 1376860
TI  - Radiation-induced bilateral cystic frontal lobe necroses demonstrating a fluid
      blood level--case report.
AB  - A 41-year-old male developed radiation-induced bilateral cystic frontal lobe
      necroses after irradiation for an olfactory neuroblastoma. Computed tomography
      (CT) and magnetic resonance (MR) imaging revealed the lesions, one containing a
      fluid-blood level on CT scans and niveau formation on MR images. It was proved to
      be a coagulated hematoma within the cyst at surgery. Such a fluid-blood level in
      a radiation-induced cyst has never been reported, although hemorrhage frequently
      accompanies delayed radiation necrosis. Positron emission tomography with
      multiple tracers may be useful in differentiating cerebral radiation necrosis
      from tumor recurrence, because of absence of abnormal tracer accumulation.

PMID- 1376861
TI  - Experimental investigation of a new liquid embolization method: enhancing effect
      of 25% ethanol on conjugated estrogen.
AB  - A new liquid embolization material applicable to intracranial lesions was
      evaluated by selective renal artery embolization in mongrel dogs. Absolute and
      diluted ethanol, estrogen, and estrogen in 25% ethanol (ethanol-estrogen) were
      injected. The embolization and side effects were investigated angiographically
      and histologically. Ethanol-estrogen caused similar embolization to absolute
      ethanol, but no direct damage to perivascular tissue, and is considered a
      promising embolization agent in intravascular surgery.

PMID- 1376862
TI  - Peritumoral brain edema associated with meningioma--histological study of the
      tumor margin and surrounding brain.
AB  - Thirty-nine cases of intracranial meningiomas were analyzed to identify factors
      causing brain edema. Edema was significantly correlated with tumor size and the
      destruction of the leptomeninges and cortex. Meningotheliomatous meningioma
      tended to have more peritumoral edema. There was no correlation between the
      presence of edema and location of the tumor or histological features including
      lymphocytic infiltration and the presence of glial fibrillary acidic protein
      positive cells in the tumor tissue. Larger tumors destroy the leptomeninges and
      cerebral cortex, allowing direct transmission of humoral edema-promoting factor
      or edema fluid into the white matter, resulting in vasogenic edema.

PMID- 1376863
TI  - Postoperative neurosurgical infection and antibiotic prophylaxis.
AB  - The most suitable antibiotics for chemoprophylaxis in neurosurgery and risk
      factors for postoperative neurosurgical infection were investigated by
      retrospective analysis of 807 neurosurgical procedures in 566 patients between
      1980 and 1989. Prophylactic antibiotics were administered intravenously for 6 or
      7 postoperative days in all instances. The 807 operations were classified
      according to the antibiotics used into: 1) penicillin, 2) cephem-I, 3) cephem-II,
      4) cephem-III, and 5) others. Postoperative neurosurgical infections occurred in
      27 of 807 operations (3.3%), or 27 of 566 patients (4.8%). Hypertension and
      surgery performed in summer carried a significantly higher risk of infection.
      Diabetes mellitus, steroid administration, prolonged surgery, re-exploration, and
      surgery for hemorrhagic cerebrovascular diseases were associated with increased
      risk, but were not statistically significant. Infection rates by type of
      chemoprophylaxis were: 3.6% in the penicillin group, 3.7% in the cephem-I group,
      1.7% in the cephem-II group, 5.7% in the cephem-III group, and 2.8% in the others
      group. This result indicates that the best choice for prophylactic antibiotic
      therapy may be a second-generation cephem.

PMID- 1376864
TI  - Acute subdural hematoma in young patient with moyamoya disease--case report.
AB  - A 17-year-old boy with known moyamoya disease developed an acute subdural
      hematoma after a mild head trauma. He had been confined to a wheelchair with
      contracture in the upper and lower extremities due to juvenile rheumatoid
      arthritis since age 1 year. He had undergone encephalo-duro-arterio-synangiosis
      (EDAS) on the right and encephalo-myo-synangiosis (EMS) on the left at 13 years
      of age. He was admitted with headache, nausea, and vomiting after a fall from his
      wheelchair at age 17. Computed tomography on admission showed a large acute
      subdural hematoma in the right fronto-temporal region but no bleeding at the EDAS
      or EMS sites. Cerebral angiography 12 weeks after the head trauma revealed a
      remarkable reduction in the spontaneous transdural external-internal carotid
      anastomoses in the right frontal region. The acute subdural hematoma was probably
      caused by rupture of the spontaneous transdural anastomoses.

PMID- 1376865
TI  - Spontaneous disappearance of arteriovenous fistula between the vertebral artery
      and deep cervical vein--case report.
AB  - A 58-year-old female was readmitted with pulsatile tinnitus in the right ear 8
      months after subtemporo-occipital transtentorial clipping of a peripheral
      superior cerebellar artery aneurysm. On examination, she was normal except for
      pulsatile bruit over the right mastoid region. Angiography showed a fistulous
      communication between the muscular branches of the right vertebral artery and the
      deep cervical vein. The incision of the aneurysm surgery was supratentorial, so
      the only possible cause of the upper cervical arteriovenous (AV) fistula was fine
      gold acupuncture needles implanted for bronchial asthma 18 years before. The AV
      fistula disappeared spontaneously after 1 month, possibly because of thrombosis
      of the affected veins.

PMID- 1376866
TI  - Bilateral symmetrical cerebral arteriovenous malformations in the basal ganglia-
      case report.
AB  - A 21-year-old male presented with visual disturbance followed by severe headache.
      Computed tomography showed right thalamic hemorrhage entering the right lateral
      ventricle. Cerebral angiography revealed bilateral symmetrical arteriovenous
      malformations (AVMs) fed by the lenticulostriate, anterior choroidal, and lateral
      posterior choroidal arteries and draining into the vein of Galen. Partial removal
      of the right AVM induced bleeding on the left side, probably due to postoperative
      hemodynamic changes. Bilateral symmetrical cerebral AVMs are extremely rare, but
      provide serious problems for surgical intervention in the deep cerebrum.

PMID- 1376867
TI  - Intracavernous cavernous hemangioma: dynamic CT findings and effectiveness of
      irradiation--case report.
AB  - An intracavernous cavernous hemangioma occurred in a 34-year-old female
      presenting with amenorrhea and hyperprolactinemia. Computed tomography (CT)
      showed a homogeneously enhanced mass in the right cavernous sinus. The time
      density curve detected by dynamic CT showed significant delayed flow in the
      lesion. The mass was significantly reduced in size by local irradiation (50 Gy).
      Dynamic CT may be useful in differentiating cavernous hemangioma, and radiation
      therapy should be considered for preferred treatment to surgical intervention.

PMID- 1376868
TI  - Sacral nerve root cysts manifesting as localized unilateral perineal pain--case
      report.
AB  - A 62-year-old female presented with multiple sacral nerve root cysts manifesting
      as localized unilateral perineal pain. Myelography just after contrast material
      injection revealed multiple cysts at the sacral level. However, perioperative dye
      injection showed hardly any flow in the reverse direction. Only the S3 nerve was
      constricted by hyperplasia of the dura mater, and adhered to the cyst wall. Other
      nerves were not constricted, nor adhered to cyst walls. The S3 nerve constriction
      and tight adhesion was the cause of the pain. The one-way flow of spinal fluid
      from the spinal subarachnoid space to the cysts is probably closely correlated
      with cyst formation.

PMID- 1376869
TI  - Distribution of HSP72 induction and neuronal death following limbic seizures.
AB  - A small area of deep prepiriform cortex is uniquely susceptible to convulsant and
      anticonvulsant drugs in the rat. We have studied the pattern of expression of the
      non-constitutive stress protein (HSP72) following seizures induced by unilateral
      microinjection of bicuculline into this area. HSP was seen first in ipsilateral
      dorsal medial thalamus, amygdala and associated piriform cortex, and with more
      sustained seizures was seen bilaterally in these structures as well as in other
      projection sites. Neuronal cell death, as assessed by acid-fuchsin staining,
      occurred in the same brain regions. Frank necrosis was found in the ipsilateral
      piriform cortex with prolonged seizures. Behaviorally, the seizures induced are
      characteristic of involvement of the limbic system and, therefore, may be a model
      of human complex partial seizures.

PMID- 1376870
TI  - Induction by nerve growth factor (NGF) of NGF receptor-like immunoreactivity in
      the preoptic area and hypothalamus of neonatal rats.
AB  - Nerve growth factor (NGF) was injected in the brain of neonatal rats. In eleven
      of thirty-one rats that received 1 microgram of mouse NGF (2.5S form) on
      postnatal day 3, NGF receptor-like immunoreactivity was found in the preoptic
      area (POA) and hypothalamus until 12 days after birth. However, no
      immunoreactivity was seen in the region of rats in the same group examined on day
      20 or 45 and of uninjected control rats on days 1-45. These results indicate that
      NGF induces the transient appearance of the receptor for NGF in the POA and
      hypothalamus of neonatal rats.

PMID- 1376871
TI  - Chronic treatment with D600 enhances development of sodium channels in cultured
      chick skeletal muscle cells.
AB  - We have studied the long-term effects of D600, a blocker of L-type voltage
      dependent Ca channels (VDCC), on the development of voltage-dependent Na channels
      (VDNC) that are sensitive to tetrodotoxin (TTX), by electrophysiological
      measurements of the maximum rate of rise of the TTX-sensitive Na spike in
      cultured chick skeletal muscle cells. Chronic treatment with D600 (2-20 microM)
      caused a dose-dependent increase in the density of VDNC. The density of VDNC was
      increased by 150-250% when D600 was added to the cultures at 20 microM from the
      second day of culture onward. Co-treatment with an inhibitor of the transcription
      of RNA from DNA, alpha-amanitin, or with cycloheximide, an inhibitor of protein
      synthesis, prevented the up-regulation by D600. Nifedipine, a different type of
      blocker of L-type VDCC, was also effective in increasing the density of VDNC, and
      BAY K 8644, an agonist of L-type VDCC, had the opposite effect. It is suggested
      that the effect of D600 was mediated via a mechanism specific for L-type VDCC
      that involves regulation of cytosolic levels of Ca2+ and protein synthesis de
      novo.

PMID- 1376872
TI  - Adenosine receptor link in an adrenal opioid-induced antinociception in the rat
      tail-flick test.
AB  - Intrathecal administration of substance P at the lower thoracic spinal level has
      an antinociceptive effect on reaction time in the tail-flick test; this response
      is blocked by naloxone i.v. but not by i.v. administration of opiate antagonists
      which do not cross the blood-brain barrier. As morphine-induced analgesia is
      blocked by adenosine antagonists, to determine whether this substance P-induced,
      opioid-mediated antinociception also includes a purine link, the adenosine
      receptor antagonist, caffeine, was given systemically 10 min prior to substance P
      administration. In control rats pretreated with saline, substance P (6.5 nmol)
      produced an increase in reaction time to about 160% of preadministration values
      at one min after intrathecal injection. The effect could also be observed at 6
      min after this injection. Pretreatment with 16 or with 32 mg/kg of caffeine i.p.
      blocked the response to substance P, and produced a hyperalgesia similar to that
      reported in studies at the lumbo-sacral spinal level. These results indicate that
      the adrenal opioid-induced antinociception observed upon intrathecal
      administration of substance P at the lower thoracic level occurs via an adenosine
      link. This is the first demonstration of a purine link in the expression of
      antinociceptive effects of an endogenously released opioid.

PMID- 1376873
TI  - Pyramidal neurons are immunoreactive for calbindin D28k in the CA1 subfield of
      the human hippocampus.
AB  - The calcium binding protein calbindin D28k (CaBP) is localized in the granule
      cells of the dentate gyrus, in pyramidal neurons of the CA1 and CA2 subfields of
      the Ammon's horn as well as in distinct groups of local circuit neurons in both
      parts of the human hippocampal formation. Immunostaining was performed on human
      brain perfused 2 h after death. The localization of CaBP in the human was found
      to be similar to that in the monkey hippocampus suggesting that there is no
      species difference in the cellular localization of CaBP among different primates.

PMID- 1376874
TI  - Stimulation of locomotor activity by intra-accumbens AMPA is not inhibited by
      neonatal 6-hydroxydopamine-induced lesions.
AB  - The involvement of dopamine in the hypermotility responses to amphetamine s.c. or
      AMPA injected into the nucleus accumbens was evaluated in adult rats depleted of
      dopamine as neonates with 6-hydroxydopamine. The hypermotility response to
      amphetamine was markedly inhibited in the lesioned animals, while that to AMPA
      was enhanced. In addition, the hypermotility produced by AMPA in these rats was
      not inhibited by sulpiride+SCH-23390; however, it was inhibited completely by
      alpha-methyl-p-tyrosine. These results suggest that the hypermotility produced by
      AMPA requires endogenous dopamine, but is mediated by a different mechanism than
      that produced by amphetamine.

PMID- 1376875
TI  - Demonstration of a direct projection from the retina to the hypothalamic
      supraoptic nucleus of the hamster.
AB  - Hamsters were injected in the left eye with unconjugated cholera toxin subunit B
      (CHB) and the tracer was localized using immunohistochemistry. A large number of
      immunoreactive fibers was found in the suprachiasmatic nuclei and the
      contralateral lateral hypothalamic area. Labeled fibers coursed around the
      supraoptic nucleus and nerve terminals accumulated in a zone dorsally and
      laterally to the nucleus. Single fibers from this plexus penetrated into the
      supraoptic nucleus, where few fibers arborized into delicate immunoreactive
      profiles possessing varicosities. Labeled fibers were identified only in the
      dorsal and lateral parts of the nucleus, and mostly at the caudal level of the
      optic chiasm. These results show a direct retinal innervation of the
      magnocellular neurons of the supraoptic nucleus, and indicate a direct photic
      influence on the hypothalamo-neurohypophysial system.

PMID- 1376877
TI  - Effects of McN-A-343 on insect neurosecretory cells: evidence for muscarinic-like
      receptor subtypes.
AB  - The muscarinic agonist McN-A-343 has been used to characterize the muscarinic
      receptors on somata of adult cockroach dorsal unpaired median (DUM) neurones
      maintained in short-term culture. Pressure application of McN-A-343 onto isolated
      DUM neurones induced a dose- and voltage-dependent biphasic response composed of
      a fast initial hyperpolarization followed by a slow depolarizing phase, recorded
      with the patch-clamp technique in the whole-cell recording configuration. The
      fast hyperpolarization reversed at an extrapolated potential value of -91.04 mV
      and was fully antagonized by the M2 muscarinic antagonist methoctramine. The slow
      depolarizing component reversed at an extrapolated value of -28.33 mV and was
      inhibited by the M1 muscarinic antagonist pirenzepine. These results demonstrate
      both a specific effect for McN-A-343 on DUM neurones and the existence of two
      functionally distinct muscarinic-like receptor subtypes governing this McN-A-343
      induced biphasic response.

PMID- 1376876
TI  - Differential effect of immunosympathectomy on the expression of rat enteric
      neurotransmitters.
AB  - The effect of immunosympathectomy on the pattern of distribution of catecholamine
      and peptide-containing nerve fibres and neurones in the myenteric and submucous
      plexuses of rat ileum was investigated. There was an increase in vasoactive
      intestinal polypeptide (VIP)-, galanin (GAL)- and substance P-like
      immunoreactivity in the myenteric plexus of ileum from rats treated with nerve
      growth factor (NGF) antiserum compared with controls. A similar increase in
      immunoreactivity was observed in VIP-, GAL- and neuropeptide Y (NPY)-containing
      submucous neurones and nerve fibres. In contrast, the immunosympathectomy had no
      effect on the pattern of distribution of catecholamine-, calcitonin gene-related
      peptide (CGRP)- and NPY-containing nerve fibres in the myenteric plexus or on
      substance P- and CGRP-containing neurones and nerve fibres of the submucous
      plexus. The findings of the present study suggest that NGF may differentially
      regulate the expression of enteric neuropeptides at a postnatal stage of
      development.

PMID- 1376878
TI  - ATP activates junctional and extrajunctional acetylcholine receptor channels in
      isolated adult rat muscle fibres.
AB  - Single-channel recordings in the cell-attached configuration were made on freshly
      dissociated and cultured rat muscle fibers. We demonstrate that ATP (50-100
      microM) elicits single channel currents in freshly isolated fibres. These ATP
      activated channels have a slope conductance similar to that determined for ACh
      activated channels but exhibit a shorter open time. We also show that ATP
      activates extrajunctional AChR-channels in the membrane of long-term cultured
      muscle fibres. Here the ATP activated channel has a slope conductance and open
      time characteristics similar to those of the ACh-activated channel.

PMID- 1376879
TI  - A comparative HRP study of the neuronal supply to the inferior and superior nasal
      meatus in the cat.
AB  - Neurons supplying the nasal mucosa in the cat were retrogradely labelled with
      horseradish peroxidase. Sensory trigeminal neurons to the inferior and superior
      nasal meati are somatotopically organized, according to the ophthalmic or
      maxillary origin of the afferents studied. Whatever their relative location, the
      cell bodies from nasal afferents were, on average, smaller than the overall cell
      population in the ganglion, in keeping with the high proportion of nasal
      receptors innervated by thin fibers. Postganglionic neurons from parasympathetic
      origin could be labelled in the sphenopalatine ganglion. These neurons probably
      supply mucosal secretory glands. They are in the same size range as the bulk of
      neurons in the same ganglia.

PMID- 1376880
TI  - Presence of gastrin-releasing peptide in neurons of the geniculate ganglion in
      rat and man.
AB  - Gastrin-releasing peptide (GRP) was demonstrated by immunohistochemistry and high
      performance liquid chromatography to be present in the great majority of neurons
      in the geniculate ganglion of rat and man. This was in contrast to findings in
      the sphenopalatine ganglion of rat, where only little GRP was found, and in the
      otic, trigeminal, glossopharyngeal-vagal and internal carotid ganglia, where no
      GRP-containing cells could be demonstrated. The peptide was not detected by
      immunohistochemistry in nerve fibers within structures innervated from the
      ganglion (tongue, soft palate, retroauricular skin and facial musculature). The
      retrograde axonal tracer True blue accumulated in these neurons of rat after
      application not only in the tongue and soft palate but also in the retroauricular
      skin.

PMID- 1376881
TI  - Hippocampal and neocortical ubiquitin-immunoreactive inclusions in amyotrophic
      lateral sclerosis with dementia.
AB  - Amyotrophic lateral sclerosis (ALS) patients with dementia were found to have
      ubiquitin-immunoreactive (IR) inclusions in the dentate granule cells of the
      hippocampus. These inclusions were also present in some patients with minor
      cognitive changes but otherwise typical ALS. Ubiquitin-IR inclusions were also
      found in neurons of superficial layers of the frontal and temporal cortex and in
      the entorhinal cortex in patients with ALS and dementia. These ubiquitin-IR
      inclusions were non-argyrophilic, and were not labelled by antibodies which
      identify Alzheimer's neurofibrillary tangles and Pick bodies, nor were they
      typical of cortical Lewy bodies. Our findings indicate that ubiquitin-IR
      inclusions in small neurons of the hippocampus, entorhinal area and neocortex are
      a characteristic feature of degeneration of non-motor cortex in ALS, and are
      particularly associated with cognitive impairment and dementia of frontal lobe
      type.

PMID- 1376882
TI  - Comparison of the inhibitory roles of neuropeptide Y and galanin on cardiac vagal
      action in the dog.
AB  - Prolonged attenuation of cardiac vagal action occurs following cardiac
      sympathetic nerve stimulation or intravenous neuropeptide Y (NPY) injections in
      anaesthetised dogs. Equimolar intravenous injections of galanin (GAL) had no
      effect on cardiac vagal action in this species. Immunohistochemical analysis of
      dog stellate ganglia and cardiac muscle showed that most nerve cell bodies
      showing tyrosine hydroxylase immunoreactivity (TH-IR) also showed
      immunoreactivity to both NPY and GAL. The results are consistent with the
      proposal that NPY released from cardiac sympathetic nerves is responsible for the
      prolonged inhibition of cardiac vagal action known to be caused by such
      stimulation. A role for GAL, shown here to exist in cardiac sympathetic nerves in
      the dog, has yet to be determined.

PMID- 1376883
TI  - Fastigiofugal fibers encoding horizontal and vertical components of saccades as
      determined by microstimulation in monkeys.
AB  - To identify the routes by which oculomotor vermis signals control eye movements
      (saccadic signals), saccades evoked by microstimulation were studied in the
      region of the uncinate fasciculus (UF) and juxtarestiform body (JB) in the
      macaque monkey. Anatomical pathways of axons from the fastigial oculomotor region
      (FOR) were studied by anterograde transport of wheatgerm agglutinin conjugated
      horseradish peroxidase (WGA-HRP). The routes were identified by comparing maps of
      low threshold for evoking saccades with the anatomical map of anterogradely
      labeled axons arising from the FOR. Microstimulation of a region of the UF and JB
      demonstrated that saccadic signals are carried exclusively by decussated FOR
      axons which leave the cerebellum via the contralateral UF. The fibers in the JB
      do not carry saccadic signals. The horizontal component of saccadic signals is
      conveyed by fibers in the descending limb of the UF, while the vertical component
      is conveyed by a smaller group of fibers which separate from the UF and enter the
      midbrain with the contralateral superior cerebellar peduncle.

PMID- 1376884
TI  - Initial uncoordinated expression of three types of voltage-gated currents in
      cultured Xenopus myocytes.
AB  - The expression of three types of voltage-gated ionic currents, namely the Na+
      inward current, K+ outward rectifier current and K+ inward rectifier current, was
      examined in cultured developing Xenopus myocytes. In the population of myocytes,
      the Na+ inward current and K+ outward rectifier current appeared at around 32 h
      after fertilization (stage 27) and gradually increased during the period of
      observation, up to more than 44 h after fertilization (stage 33/34). The
      developmental time course of these two types of currents was similar. However,
      during the transition period individual myocytes did not necessarily express
      these two types of currents in a coordinated fashion. Some myocytes had a large
      Na+ inward current and small K+ outward rectifier current or vice versa. The K+
      inward rectifier current was observed in some cells earlier than stage 27 and
      also gradually increased during the observation period. The initial expression of
      this current was not correlated with the K+ outward rectifier current or with the
      Na+ inward current.

PMID- 1376885
TI  - K+ channel involvement in induction of synaptic enhancement by mast cell
      degranulating (MCD) peptide.
AB  - A bee venom, mast cell degranulating peptide (MCD), which induces long-term
      potentiation (LTP) of synaptic transmission in hippocampal slices, was found to
      possess multiple functions. They include (1) binding and thereby inhibiting a
      voltage-dependent K(+)-channel in brain membranes, (2) incorporation in a lipid
      bilayer to form voltage-dependent and cation-selective channels by itself, and
      (3) activation of a pertussis toxin (Ptx)-sensitive GTP-binding proteins. In this
      study, we prepared several derivatives and analogues of MCD and investigated
      which function is more closely related to the induction of LTP. Another bee
      venom, apamin, formed ion channels in a lipid bilayer which were
      indistinguishable from those formed by MCD. D-MCD, an optical isomer of MCD,
      activated a Ptx-sensitive GTP-binding protein. However, these peptides did not
      induce LTP in the hippocampal slices. A snake venom, dendrotoxin-I (DTX-I), bound
      to the same K(+)-channels as MCD and did induce LTP. These results suggest that
      the most potent aspect of MCD involved in LTP inducibility is its interaction
      with the voltage-dependent K(+)-channel.

PMID- 1376886
TI  - Clinical and cytologic aspects of ocular late-phase reaction in the guinea pig.
AB  - Conjunctival tissue of 12 guinea pigs (6 experimental animals, 6 controls) was
      sensitized with IgG1 (PCA titer 1:2,000) antisera to dinitrophenol carrier and
      challenged topically with hapten. Periorbital swelling, conjunctival edema and
      conjunctival redness were evaluated clinically at 0.5 h and hourly for 12 h, and
      again at 24 and 48 h. Tears were collected at each time point for cytology.
      Results showed an early-phase reaction (EPR) peaking at 0.5 h and a late-phase
      reaction (LPR) peaking at 5-7 h. Periorbital swelling was minimal 4 h after
      appearance of the EPR. Conjunctival edema and redness increased in both the early
      and late phases, but without two distinct peaks. However, individual animals in
      both groups did show biphasic reactions. Tear cytology showed an abnormal
      increase in neutrophils and eosinophils in the later time periods and was a
      significant way to detect ocular anaphylaxis. In conclusion, if the presence of
      two significant peaks of clinical inflammation after one antigen challenge is
      taken as the narrowest definition of a late phase in anaphylaxis, our results
      show an ocular LPR occurring in our animal model.

PMID- 1376887
TI  - Clonazepam treatment of myoclonic contractions associated with high-dose opioids:
      case report.
AB  - A 30-year-old man with chronic abdominal pain was treated with high doses of
      hydromorphone intravenously and developed severe and frequent myoclonic
      contractions. Several medications including lorazepam failed to control the
      contractions; however, clonazepam in normal doses reduced the myoclonus
      dramatically.

PMID- 1376888
TI  - Effects of intrathecal antibodies to substance P, calcitonin gene-related peptide
      and galanin on repeated cold stress-induced hyperalgesia: comparison with
      carrageenan-induced hyperalgesia.
AB  - Rats exposed to a cold environment (4 degrees C) for 30 min every 1 h during the
      day and at night show a gradual decrease in the nociceptive threshold for
      pressure stimulation. Such hyperalgesia, referred to as repeated cold stress
      (RCS)-induced hyperalgesia, is stable for at least 4 h and maintained for 3 days
      only by exposing to cold overnight; thus, no adaptation to RCS is apparent.
      Hyperalgesia gradually returns over 4 days after cold exposure ceases. To
      determine whether three neuropeptides, substance P (SP), calcitonin gene-related
      peptide (CGRP) and galanin (GAL), which are present in the superficial dorsal
      horn including primary afferent terminals, would be responsible for RCS-induced
      hyperalgesia, we examined the effects of intrathecal injections of their
      antibodies (used as inhibitors of neuropeptide-mediated synaptic transmission) on
      the nociceptive threshold of RCS rats, and compared this with the antibody effect
      on carrageenan-induced hyperalgesia. An intrathecal injection of anti-SP antibody
      significantly inhibited the hyperalgesia of RCS rats as well as carrageenan
      induced hyperalgesia, and slightly increased the nociceptive threshold of non-RCS
      rats. Anti-CGRP antibody produced an improvement in the hyperalgesia of RCS rats
      as well as carrageenan-induced hyperalgesia without having an effect on the
      nociceptive threshold of non-RCS rats. Although anti-GAL antibody significantly
      inhibited carrageenan-induced hyperalgesia, it did not affect the nociceptive
      threshold of RCS and non-RCS rats. The present results suggest that enhancement
      of synaptic transmission mediated by SP and CGRP, but not GAL, in the spinal
      dorsal horn is, at least in part, involved in RCS-induced hyperalgesia.

PMID- 1376889
TI  - [The keratinocyte].
AB  - This review summarizes recent data on the keratinocyte, the major cell type in
      the epidermis. A two-state model is proposed: in the "resting" state, the
      keratinocyte is committed to a program of terminal differentiation focusing on
      production of an efficient barrier, the stratum corneum, and of the epidermal
      basement membrane; the activated state, first discovered in cell culture studies,
      occurs in vivo during epidermal wound healing and inflammatory skin diseases.

PMID- 1376890
TI  - [Biophysical characterization of the stratum corneum. Relationship between
      structure and properties].
AB  - Studies carried out over the last ten years have determined the structure and
      chemical composition of the stratum corneum and their significance for biologic
      function; the stratum corneum (SC) is composed of flat layers linked to each
      other by desmosome plates. Intercellular spaces are composed mainly of double
      lipid layers which are responsible for the main part of the barrier function of
      the SC. This barrier between the body and the environment must be effective
      despite the deformations and various insults (chemical, physicochemical) to which
      the SC is subjected. The SC fulfills its barrier function through remarkable
      physical properties of which most originate in an ability to bind water molecules
      to protein sites whose presence depends on the humidity of the environment in
      which the SC was produced. Lastly, the SC exhibits some enzyme activities and
      consequently can no longer be considered as an inert membrane.

PMID- 1376891
TI  - 2-5A synthetase expression in mice infected with Trypanosoma cruzi.
AB  - This study describes the production and action of interferon in mice infected
      with Colombian and Y strain T. cruzi. The production of interferon was monitored
      by an in vitro assay of plasma and extract of spleen, lung and heart for
      interferon activity. The action of interferon in mice was assessed by measuring
      an interferon-mediated enzyme activity, 2-5A synthetase. Infected mice (strain
      Balb/c) were sacrificed at different time intervals, and the level of this enzyme
      was measured in extracts of spleen, lung and heart. Colombian strain infection
      induced higher levels of interferon than Y strain under the same conditions;
      consequently, a greater increase in 2-5A synthetase induction was observed in the
      former of the two strains. These results suggest that interferon produced by T.
      cruzi infected mice is active, since a variety of organs respond to its presence
      by producing elevated levels of 2-5A synthetase.

PMID- 1376892
TI  - [Interactions between peptides and major histocompatibility complex molecules].
AB  - T-cell receptors recognize foreign proteins as peptide fragments associated with
      major histocompatibility complex (MHC) molecules. Properties of antigenic
      peptides, methods for detecting peptide-MHC molecule combinations, and the
      characteristics of the interaction are reviewed. Possible explanations for graft
      rejection and autoimmune disease are suggested in the light of these data.

PMID- 1376893
TI  - Shock strength for the implantable defibrillator: can you have too much of a good
      thing?

PMID- 1376894
TI  - Tachycardia sensing failure of an implantable cardioverter defibrillator in a
      patient with hypertrophic cardiomyopathy.
AB  - A 17-year-old white male was found to have nonobstructive hypertrophic
      cardiomyopathy after suffering three severe syncopal episodes. He experienced an
      episode of sustained polymorphic ventricular tachycardia during exercise
      tolerance testing that required cardioversion. Electrophysiological studies were
      able to reproduce sustained polymorphic ventricular tachycardia that was
      unresponsive to standard pharmacotherapy. An automatic implantable defibrillator
      was placed. However, during implantation with the rate sensing electrodes on the
      left ventricle, it was found that the extremely polymorphic nature of the
      tachycardia caused such rapid fluctuations in the sensed R wave signal that the
      device could not properly detect the tachycardia. This was felt to be due to the
      automatic gain control circuit of the Ventak 1550. The problem was solved by
      moving the rate sensing electrodes to the lateral right ventricle. This case
      suggests that the unique arrhythmic substrate of hypertrophic cardiomyopathy may
      present sensing difficulties during automatic implantable defibrillator
      insertion.

PMID- 1376895
TI  - Bedside termination of sustained ventricular tachycardia by transesophageal
      atrial pacing.
AB  - Transesophageal atrial pacing was used to terminate hemodynamically stable
      sustained monomorphic ventricular tachycardia in two patients. The procedure was
      performed at the bedside, no anesthesia was required, there were no
      complications, and one of the patients went home after the procedure was
      performed. This method should be considered prior to using direct current
      cardioversion in patients with hemodynamically stable sustained monomorphic
      ventricular tachycardia.

PMID- 1376896
TI  - Intraoperative identification of a radiofrequency lesion allowing validation of
      catheter mapping of ventricular tachycardia with a computerized balloon mapping
      system.
AB  - Radiofrequency current was utilized to mark the anatomic location of earliest
      endocardial activation during catheter mapping of ventricular tachycardia.
      Intraoperative identification of the radiofrequency lesion allowed validation
      that the site of earliest endocardial activation determined by a catheter mapping
      study was the same as assessed by a computerized balloon mapping system.
      Radiofrequency current may be a useful method of marking areas of endocardium
      thought to be potential sites for ablative surgery as well as allowing
      correlation between different mapping techniques.

PMID- 1376897
TI  - Ventricular fibrillation produced by stimulation of external transthoracic
      electrodes--an experimental study.
AB  - The threshold for ventricular fibrillation was determined in 12 pentobarbital
      anesthetized dogs using transthoracic electrodes located at the optimal axillary
      electroventilation sites. Electroventilation is the name used to designate
      inspiration produced by stimuli applied to body surface electrodes. The optimal
      stimulation site for electroventilation was first determined using hand-held
      electrodes. Then electrodes, 4.1 cm in diameter, were sutured bilaterally to the
      optimal anterior axillary stimulation site. The threshold current for producing
      ventricular fibrillation was determined using single pulses ranging from 0.1-10
      msec in duration delivered during the vulnerable period of the cardiac cycle.
      Fibrillation was produced in all dogs with the 10- and 5-msec pulse durations, in
      11 dogs with 0.3-msec, in 6 dogs with 0.2-msec, and in 1 dog with 0.1-msec pulse
      duration. In all dogs, the current required to produce ventricular fibrillation
      increased greatly as the pulse duration was decreased. The current required for
      fibrillation was much in excess of that required to produce one tidal volume.
      With the longer duration pulses, the ratio was about 80. With the 8 microseconds
      duration pulses used for electroventilation the estimated ratio is about 800.

PMID- 1376898
TI  - Slowing of ventricular tachycardia as a possible endpoint for serial drug testing
      at electrophysiological study.
AB  - Certain patients who cannot be rendered noninducible by serial drug testing
      during electrophysiology study demonstrate significant slowing of their
      ventricular tachycardia rate with selected agents. We evaluated the
      characteristics and outcome of 19 such patients to assess whether this slowing
      could be considered an acceptable endpoint for treatment. This group consisted of
      14 males and 5 females (mean age 63 +/- 9) with a mean ejection fraction of 28 +/
      13% and inducible sustained ventricular tachycardia. Sixteen patients had known
      coronary artery disease and 13 had prior myocardial infarction. The other three
      patients had idiopathic cardiomyopathy. Serial drug testing during an
      electrophysiology protocol that used up to three extrastimuli at two or three
      cycle lengths at two right ventricular sites was used to select a medication
      regimen that provided optimal ventricular tachycardia slowing without limiting
      side effects. Five patients were treated with amiodarone, three with Ic agents
      (all with ejection fraction greater than 30%), and the remainder with Ia and Ib
      agents alone or in combination. Mean initial ventricular tachycardia rate was 219
      +/- 26 beats/min with posttreatment ventricular tachycardia rate 137 +/- 17 (mean
      initial cycle length 278 +/- 35 msec, posttreatment 443 +/- 53 msec). Two groups
      were identified, those who had recurrent (although well-tolerated) ventricular
      tachycardia (group I, n = 8, mean time to recurrence = 15 months), and those who
      did not (group II, n = 11, mean follow-up 22 months). Overall sudden death rate
      was 5%, while total mortality was 11% (all mortality in group I).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1376899
TI  - Clinical evaluation of the safety of repetitive intraoperative defibrillation
      threshold testing.
AB  - One goal of the initial implantation procedure for a cardioverter defibrillator
      is determination of the configuration and patch location with the lowest
      defibrillation threshold (DFT). To determine the safety of multiple
      defibrillation tests, an analysis of the intraoperative defibrillation threshold
      tests (DFTT) in our patients was performed. In 84 patients, the mean number of
      DFT trials was 5.27; the mean number of joules received was 275.0. The maximum
      number of shocks in one implant procedure was 50 for a total of 4,895 joules
      without complications. Four patients received 30 or more DFT shocks without
      complication. There were two complications related directly to the DFTT: one
      patient with severe noninflammatory cardiomyopathy developed electromechanical
      dissociation and was subsequently resuscitated and survived; the second patient
      with severe triple vessel coronary artery disease suffered an intraoperative
      myocardial infarction during testing and eventually died 22 days postoperatively.
      All patients received an ICD unit; six patients had DFTs of greater than 20
      joules. Based on our experience, we followed the clinical status (heart rate,
      blood pressure, ECG changes, fluid status, total anesthesia time) during the DFTT
      to determine the extent and duration of our testing protocol. Multiple shocks due
      to repositioning of the leads in a stable patient should not prohibit extensive
      testing as adverse consequences do not appear to be cumulative.

PMID- 1376900
TI  - Relationship between beat-to-beat changes in hemodynamic state and action
      potential duration of the left ventricle during rapid ventricular pacing in man.
AB  - A relationship between beat-to-beat changes in hemodynamic state and action
      potential duration (APD) of the left ventricle was studied by pacing the right
      ventricle with a constant cycle length (400 msec) for 3 minutes and recording
      simultaneously the intraarterial pressure and left ventricular monophasic action
      potential in 16 patients (mean age 51 +/- 8 years) undergoing routine cardiac
      catheterization. The APD measured at the point of 90% repolarization (APD-90)
      shortened gradually from a baseline value of 305 +/- 25 msec to a minimum of 246
      +/- 25 msec (P less than 0.001) by 160 +/- 10 seconds after the onset of pacing.
      After reaching the minimum duration, the APD and blood pressure were measured
      from 30 consecutive beats. The magnitude of beat-to-beat variation in the APD was
      directly correlated to variation in the mean arterial blood pressure (r = 0.65, P
      less than 0.01). Beat-to-beat changes in hemodynamic and electrical state were
      related in that an increase of at least 10 mmHg in the blood pressure of one beat
      was associated with an increase in the APD of the concomitant beat by at least 5
      msec. In six patients with ventriculoatrial dissociation during the rapid
      ventricular pacing, the sequential ventriculoatrial pacing decreased the beat-to
      beat variation of APD from 2.8% +/- 1.4% to 0.8% +/- 0.7% (P less than 0.01) and
      variation of blood pressure from 6.4% +/- 3.2% to 1.4% +/- 0.9% (P less than
      0.01). The observed association between beat-to-beat changes in hemodynamic state
      and APD of the left ventricle demonstrates that an immediate force-interval
      relationship exists in the human left ventricle.

PMID- 1376901
TI  - Adaptive rate pacing controlled by the right ventricular preejection interval:
      clinical experience with a physiological pacing system.
AB  - In the Precept pacing system, the right ventricular intracardiac impedance
      waveform is used to evaluate either of two indicators of metabolic demand
      relative right ventricular stroke volume and preejection interval (PEI). PEI is
      known to reliably parallel contractility changes, which is reflective of physical
      and emotional stress. The stability and dynamic behavior of PEI were tested in
      ten patients with a Precept pacing system under various forms of exercise and
      during postural changes. Although significant patient-to-patient variability of
      the sensor values was observed, reflecting individual physiological differences,
      the chronic stability of PEI was excellent in the total device experience of 147
      months. In all patients, PEI shortened significantly during bicycle ergometry
      from a mean value of 137.7 +/- 17.8 (range 96-162) to a mean value of 103.0 +/-
      21.6 (range 92-109) (P less than 0.05). Low level bicycle exercise of short
      duration resulted in a prompt decrease in PEI and increase in pacing rate in all
      patients. There were no uniform postural responses overall, although some posture
      related rate changes were observed in two patients. We conclude that the first
      generation of a PEI based pacing system holds promise for adaptive rate pacing.

PMID- 1376902
TI  - The value of transesophageal atrial pacing in predicting the efficacy of
      antiarrhythmic drugs in patients with paroxysmal narrow QRS complex tachycardia.
AB  - Transesophageal atrial pacing (TAP) is used in the diagnosis and treatment of
      paroxysmal narrow QRS complex tachycardia (NQT). The aim of this study was to
      assess the value of this technique in predicting the efficacy of antiarrhythmic
      therapy. The study group consisted of 30 consecutive patients with spontaneous
      NQT whose clinical tachycardia was inducible by TAP. Baseline TAP was performed
      off all antiarrhythmic medication and repeated during oral antiarrhythmic drug
      therapy. The pacing protocol consisted of three stages: a single extrastimulus
      introduced at progressively shorter coupling intervals during sinus rhythm,
      pacing at incremental rates to the point of second-degree AV block, and bursts of
      rapid pacing. On repeat stimulation while on oral antiarrhythmic therapy (37
      pacing studies) NQT was still inducible in 12 cases. During the follow-up period
      ten patients developed a recurrence of NQT:nine cases out of 12 (75%), in whom
      NQT was inducible while on antiarrhythmic therapy, and one case out of 25 (4%),
      in whom NQT was not inducible (P less than 0.001). The sensitivity of TAP in
      predicting the outcome of the patients with NQT was 90%, and the specificity 89%.
      The negative predictive value of TAP (prediction of no recurrence of NQT) was
      96%, and the positive predictive value (prediction of recurrence of NQT) was 75%.
      We conclude that TAP is a simple and accurate method for predicting the efficacy
      of antiarrhythmic treatment in patients with NQT.

PMID- 1376903
TI  - A double-blind study of submaximal exercise tolerance and variation in paced rate
      in atrial synchronous compared to activity sensor modulated ventricular pacing.
AB  - To assess the variation in paced rate during everyday activity and the importance
      of atrioventricular synchronization (AV synchrony) for submaximal exercise
      tolerance, atrial synchronous (DDD) and activity rate modulated ventricular
      (VVI,R) pacing were compared in 17 patients with high degree AV block. The
      patients were randomly assigned to either mode and evaluated by treadmill
      exercise to moderate exertion and by 24-hour Holter monitoring after 2 months in
      the DDD and VVI,R modes, respectively. At the end of the study, the patients were
      programmed to the pacing mode corresponding to the preferred study period. During
      the treadmill test, the mean exercise time to submaximal exertion (Borg 5/10),
      exertion ratings and respiratory rate did not differ between pacing modes despite
      a significantly lower ventricular rate in the VVI,R mode. The atrial rate during
      VVI,R pacing was significantly higher than the ventricular rate, but did not
      differ from the ventricular rate during DDD pacing. There was a diurnal variation
      in paced rate in both pacing modes. Paced ventricular rate was, however, higher
      and variation in paced rate greater in DDD compared to VVI,R pacing. Nine
      patients preferred the DDD mode, three patients preferred the VVI,R mode, while
      five subjects did not express any preference. The results from this study
      indicate that the variation in paced rate during activity sensor-driven VVI,R
      pacing does not match that during DDD pacing neither during everyday activities
      nor during submaximal treadmill exercise. Nevertheless, no differences in
      exercise time, Borg ratings, and respiratory rate during submaximal exercise were
      found. Thus, for most patients with high degree AV block, DDD and VVI,R pacing
      seem equally satisfactory for submaximal exercise.

PMID- 1376904
TI  - TU alternans, long QTU, and torsade de pointes: clinical and experimental
      observations.
AB  - T or U wave alternans in association with long QTU and torsade de pointes (TdP)
      is uncommon and its mechanism(s) is unknown. We studied three patients with TU
      alternans, long QTU, and TdP: patient 1 was a newborn with congenital long QTU;
      patient 2 had marked hypokalemia and hypomagnesemia; and patient 3 was receiving
      procainamide. In the three patients, TU alternans was tachycardia dependent and
      preceded the onset of TdP. In the patient on procainamide, TU alternans and TdP
      occurred at long cardiac cycles. In this patient, endocardial monophasic action
      potential (MAP) recordings showed that TU alternans was associated with
      alternation of the duration of the plateau. A deflection consistent with early
      afterdepolarization (EAD) arose at a constant time interval from phase 0 but
      alternated from high and low levels of phase 3. The first ectopic beat of TdP
      arose on the descending limb of the EAD. TU alternans was investigated by MAP
      recordings in six normal dogs, following the administration of anthopleurin-A (AP
      A), a drug shown to delay sodium inactivation and to induce bradycardia dependent
      long QTU, EADs, and TdP. In two dogs TU alternans was associated with 2:1
      recordings of EAD and nearly constant plateau duration. In three dogs, TU
      alternans was associated with EAD that occurred in consecutive beats at constant
      time intervals from phase 0, but alternated from high and low phase 3 because of
      alternation of the duration of the plateau. In one dog, alternation of EAD and
      plateau duration occurred. In 36 separate episodes of TdP that were analyzed in
      the six dogs, 32 were bradycardia dependent but four developed on abrupt
      shortening of the cardiac cycle associated with alternation of action potential
      duration. Our results suggest: (1) TU alternans may be due to 2:1 propagation of
      an EAD or to alternation of the recovery kinetics of a repolarization current;
      (2) The constant occurrence of EAD in relation to phase 0 in spite of alternation
      of plateau duration suggests an ionic mechanism synchronized to depolarization;
      (3) Tachycardia dependent TdP in clinical and experimental examples of long QTU
      seems to be characteristically associated with TU alternans. Dispersion of
      repolarization may underlie the increased ventricular electrical instability in
      these cases.

PMID- 1376905
TI  - Defibrillation threshold: clinical utility and therapeutic implications.

PMID- 1376906
TI  - Effect of successful coronary angioplasty on the signal-averaged
      electrocardiogram.
AB  - The effect of successful coronary artery angioplasty on the signal-averaged
      electrocardiogram (SAECG) was examined in 50 patients (41 men, 9 women, aged 55
      +/- 8 years) with stable (26 patients) or unstable angina (24 patients) and good
      overall left ventricular function (ejection fraction = 55% +/- 8%). The SAECG was
      recorded before and within 24-48 hours after the angioplasty and was filtered at
      40-250 Hz, with 250 beats averaged. The noise level averaged 0.57 +/- 0.15 microV
      before and 0.56 +/- 0.17 microV after the procedure. There was no overall
      significant difference between pre- and postangioplasty SAECGs. Subgroup analysis
      showed that 14 patients had a significant increase of the root mean square
      voltage of the last 40 msec of the filtered QRS that was independent of noise
      level changes, previous myocardial infarction, stable or unstable angina status,
      positive or negative baseline SAECG, or vessel being dilated. Eleven patients
      (22%) had late potentials at baseline, of whom four (36%) lost them after
      angioplasty, while one patient developed them after the procedure, all due to
      root mean square voltage changes. Thus, successful angioplasty exerted no
      significant overall effect on the SAECG, suggesting that the substrate of late
      potentials was not grossly altered by the procedure in our patients. However,
      there appear to be some patients, constituting approximately one third of this
      study population, who derive a favorable influence on the SAECG from angioplasty,
      a subgroup that needs to be further defined in future studies.

PMID- 1376907
TI  - Syncope--brain or heart? A case report.
AB  - A 44-year-old man suffered from recurrent episodes of unconsciousness, without
      any other concomitant manifestations. After routine workup, EEG and CT had proven
      nondiagnostic, prolonged Holter monitoring revealed a single episode of asystole,
      lasting 7.6 seconds. A pacemaker was inserted but did not abolish his episodic
      syncope. Subsequently, long-term EEG recording revealed epileptiform activity
      with independent foci in both temporal lobes. Antiepileptic treatment relieved
      the patient of his symptoms. This case illustrates the intimate relationship
      between the heart and the brain that sometimes lies behind syncope.

PMID- 1376908
TI  - The next step in cardiac pacing: the view from 1958.
AB  - At a 1-day conference sponsored by the Rockefeller Institute in September 1958,
      physicians and engineers held a confused debate over future directions for the
      young field of cardiac pacing. Many of the existing impediments to long-term
      pacing for chronic illness received little attention; the participants focused
      instead on whether atrial synchrony would be a requirement for long-term pacing.
      The Rockefeller conference illustrates the observation that cardiac pacing has
      undergone several major redefinitions. This process is rarely a smooth one but
      involves uncertainty, intense debate, and explicit choice.

PMID- 1376909
TI  - Anti-desmin vs. anti-actin for quantifying the area density of prostate smooth
      muscle.
AB  - Anti-desmin and anti-actin are commercially available antibodies that bind to
      smooth muscle. The present study was designed to compare the staining properties
      of anti-desmin and anti-actin in the human prostate in order to determine the
      optimal antibody for quantifying the smooth muscle content of the human prostate.
      Nineteen male subjects with symptomatic BPH underwent needle biopsy of the
      prostate. Double-immunoenzymatic staining was performed with peroxidase-anti
      peroxidase (PAP) and alkaline phosphatase-anti-alkaline phosphatase (APAAP)
      techniques. Rabbit anti-desmin:mouse anti-human prostatic acid phosphatase and
      mouse anti-actin:rabbit anti-human prostatic acid phosphatase were utilized.
      Computer assisted color image analysis was performed using the Bioquant image
      analysis system. The percent area density of stroma and epithelium was
      independent of the antibodies used. The percent area density of smooth muscle in
      the anti-actin stained tissue sections was twofold greater than the anti-desmin
      stained tissue sections. A direct relationship was observed for the area density
      of smooth muscle (r = 0.71; P = 0.0006) and the area density of connective tissue
      (r = 0.82; P less than 0.001) determined from anti-desmin and anti-actin stained
      tissue sections. Anti-actin represents the optimal antibody for quantifying the
      area density of prostate smooth muscle. The reproducibility of the
      immunoenzymatic staining technique is inferred from the direct relationship
      observed for area density of epithelium between the different staining
      techniques.

PMID- 1376911
TI  - Immunohistochemistry and biochemistry in detection of androgen, progesterone, and
      estrogen receptors in benign and malignant human prostatic tissue.
AB  - The relative distribution of androgen (AR), progesterone (PR), and estrogen
      receptors (ER) was localized and estimated in human prostate tissue by
      immunohistochemistry in five normal tissue samples, in eight benign hyperplastic
      (BPH) samples, in nine primary cancers, and in seven prostate cancer metastases.
      Moreover, three prostatic cancer cell lines (LNCaP, DU 145, and PC 3) were
      analyzed. A comparison between the results obtained by radioligand binding assays
      and immunohistochemistry was performed for the AR and PR. Using
      immunohistochemistry, the AR was exclusively detected in the nuclei of both
      benign and malignant prostatic epithelial cells. The highest proportion of AR
      positive cells was found in BPH and in prostate cancer metastases as compared
      with normal prostatic tissue. In a majority of the cases, the PR was only present
      in the nuclei of stromal cells. Benign hyperplastic prostates contained higher
      proportions of PR-positive cells as compared with primary carcinoma. PR was
      sparse in epithelial cells. ER-positive stromal cell nuclei were only detected in
      carcinomatous prostates. A few ER-positive epithelial cell nuclei were found in
      one sample each of a BPH and normal prostate. All cells from the androgen
      dependent, LNCaP, cell line and a majority of the cells from the androgen
      independent, DU 145, cell line were AR-positive. In contrast, the cells from the
      androgen-independent, PC 3, cell line were all AR-negative. All three cell lines
      were PR- and ER-negative. The radioligand binding technique detected the AR in
      extracts from both the cytosol and the nucleus. Again BPH contained higher
      amounts of AR as compared with normal prostatic tissue. The LNCaP cells contained
      high amounts of cytosolic AR while cells from the DU 145 and PC 3 cell lines
      lacked detectable AR as estimated by biochemical techniques. There seemed to be a
      discrepancy between biochemically measured and immunohistochemically estimated
      receptor content.

PMID- 1376912
TI  - Prognostic significance of antigenic heterogeneity, Gleason grade, and ploidy of
      lymph node metastases in patients with prostate cancer.
AB  - We retrospectively evaluated 51 prostate cancer patients found to have pelvic
      lymph node metastases at the time of pelvic lymphadenectomy and 125I
      implantation. All of them were followed until death or for a minimum of 70
      months. Rabbit polyclonal anti-PSA, anti-PAP, anti-PSP-94, and mouse TURP-27
      monoclonal antibodies were used in immunohistochemical evaluation of the
      metastatic lesions. In addition, Gleason grade and ploidy were assessed and
      correlated. No tumor with a Gleason grade of less than 7 could be found in the
      metastatic lymph nodes. Time to progression (P = .003), disease-specific survival
      (P = .009), and overall survival (P = .003) were significantly shorter in
      patients whose tumors had a primary Gleason pattern of 5 (grade 9 or 10). In the
      PSA study, patients whose tumors were reactive in more than 75% of cancer cells
      experienced significantly longer survival than those with less than 75% of cancer
      cells expressing PSA (P = .0006 log rank test). The means of overall survival +/-
      SEM were 71.5 +/- 5.0 and 34.9 +/- 5.4 months, respectively. Similar correlations
      were found with disease-specific survival and time to progression. Patterns of
      PAP expression and TURP-27 reactivity were not prognostically useful, whereas PSP
      94 expression may add some additional information. These data suggest that
      evaluation of tissue PSA heterogeneity in lymph node metastases may offer
      additional prognostic information on prostate cancer patients. Better prediction
      of individual prognosis may be possible with the combined use of Gleason grade,
      flow cytometry, and PSA expression.

PMID- 1376910
TI  - Inhibition of growth of PC-82 human prostate cancer line xenografts in nude mice
      by bombesin antagonist RC-3095 or combination of agonist [D-Trp6]-luteinizing
      hormone-releasing hormone and somatostatin analog RC-160.
AB  - The effects of treatment with a bombesin receptor antagonist [D-Tpi6, Leu13 psi
      (CH2NH) Leu14]BN(6-14)(RC-3095) and the combination of an agonist of luteinizing
      hormone-releasing hormone [D-Trp6]-LH-RH and somatostatin analog D-Phe-Cys-Tyr-D
      Trp-Lys-Val- Cys-Trp-NH2 (RC-160) were studied in nude mice bearing xenografts of
      the hormone-dependent human prostate tumor PC-82. During the 5 weeks of
      treatment, tumor growth was decreased in all treated groups compared with
      controls. Bombesin antagonist RC-3095 and the combination of [D-Trp6]-LH-RH and
      RC-160 caused a greater inhibition of tumor growth than [D-Trp6]-LH-RH or RC-160
      alone as based on measurement of tumor volume and percentage change in tumor
      volume. The largest decrease in tumor weight was also seen in the groups treated
      with the bombesin antagonist and with the combination of RC-160 and [D-Trp6]-LH
      RH. Serum prostatic-specific antigen levels were greatly decreased, and insulin
      like growth factor I (IGF-I) as well as growth hormone levels were reduced in all
      treated groups. Specific binding sites for [D-Trp6]-LH-RH, epidermal growth
      factor (EGF), IGF-I, and somatostatin (SS-14) were found in the tumor membranes.
      Receptors for EGF were significantly down-regulated by treatment with the
      bombesin antagonist or RC-160. Combination of LH-RH agonists with somatostatin
      analog RC-160 might be considered for improvement of hormonal therapy for
      prostate cancer. The finding that bombesin antagonist RC-3095 inhibits the growth
      of PC-82 prostate cancer suggests the merit of further studies to evaluate the
      possible usefulness of antagonists of bombesin in the management of prostatic
      carcinoma.

PMID- 1376913
TI  - Inhibitory effect of dicumarol on the excitability of the sarcolemma of skeletal
      muscle.
AB  - Dicumarol (7.5 x 10(-6) M -7.5 x 10(-5) M) inhibited the twitches and the
      simultaneously recorded electromyogram of the indirectly stimulated rat diaphragm
      preparation. The directly stimulated curarized preparation was inhibited in a
      similar way. Accordingly, the excitability of the sarcolemma was inhibited by
      dicumarol. The inhibitory effect was irreversible upon washing. Intracellular
      microelectrode recordings disclosed that the inhibitory effect was accompanied by
      a depolarization, and the inhibition was potentiated in high K+ (9.5 mM)
      solution. In addition, the ability of the preparations to produce a
      depolarization contracture with KCl (100 mM) was inhibited by dicumarol.
      Therefore, a part of the inhibitory effect might be caused by the depolarization.
      On the other hand, subthreshold direct stimulation disclosed that the inhibitory
      effect might be due to an increase of the threshold. However, a lack of
      synergistic interaction with lidocaine (0.2 mM) showed that this effect of
      dicumarol was probably not a membrane stabilizing or local anaesthetic effect.

PMID- 1376914
TI  - Lindane induced rat liver lipid peroxidation without depressed Cu-Zn superoxide
      dismutase activities.

PMID- 1376916
TI  - Parathyroid hormone-related protein in the rat urinary bladder: a smooth muscle
      relaxant produced locally in response to mechanical stretch.
AB  - Parathyroid hormone-related protein (PTHrP) gene expression in the pregnant rat
      uterus has been shown to be dependent on occupancy of the uterus by the fetus. To
      further test the hypothesis that the synthesis of PTHrP in smooth muscle tissue
      is regulated by mechanical stretch, we conducted experiments using the rat
      urinary bladder as a model of an expansible hollow organ. The results indicate
      that PTHrP mRNA levels do change in response to the stretch of the bladder wall.
      Under normal conditions PTHrP mRNA levels in the bladder correlated with the
      urine volume-namely, the extent of bladder distension. When bladders were
      maintained empty in vivo, PTHrP mRNA levels decreased gradually. Conversely, when
      bladders were distended by the accumulation of urine, levels of PTHrP mRNA
      increased dramatically with time. When distension was limited to one-half of the
      bladder, the increase in PTHrP mRNA was observed only in the distended portion.
      Histochemical studies performed on distended bladder tissue indicated the
      presence of PTHrP immunoreactivity in smooth muscle cells. Isolated organ bath
      studies were used to examine the possible physiological role of PTHrP in smooth
      muscle tonicity. In vitro responsiveness of bladder muscle strips to exogenous
      PTHrP was dependent on the in vivo condition of the bladder. In muscle strips
      obtained from bladders kept empty in vivo, PTHrP-(1-34)-NH2 relaxed carbachol
      induced contraction in a dose-dependent manner but failed to relax the
      contraction in muscle strips from distended bladders that had high endogenous
      PTHrP expression. These results and the previous findings in the rat uterus
      suggest a physiological role of PTHrP in bladder smooth muscle function.

PMID- 1376915
TI  - Reversible alterations in myocardial gene expression in a young man with dilated
      cardiomyopathy and hypothyroidism.
AB  - Thyroid hormone effects on myocardial gene expression have been well defined in
      animal models, but their relationship to the pathogenesis of cardiac dysfunction
      in hypothyroid humans has been uncertain. We evaluated a profoundly hypothyroid
      young man with dilated cardiomyopathy. Before and during 9 months of thyroxine
      therapy, serial assessment of myocardial performance documented substantial
      improvements in the left ventricular ejection fraction (16-37%), left ventricular
      end-diastolic diameter (7.8-5.9 cm), and cardiac index (1.4-2.7 liters.min-1.m
      2). Steady-state levels of mRNAs encoding selected cardiac proteins were measured
      in biopsy samples obtained before and after thyroxine replacement. In comparison
      with myocardium from nonfailing control hearts, this patient's pretreatment alpha
      myosin heavy-chain mRNA level was substantially lower, the atrial natriuretic
      factor mRNA level was markedly elevated, and the phospholamban mRNA level was
      decreased. All of these derangements were reversed 9 months after restoration of
      euthyroidism. These observations in an unusual patient with profound myxedema and
      cardiac dilatation permit correlation between the reversible changes in
      myocardial function and steady-state mRNA levels in a cardiomyopathy. They
      suggest that alterations in gene expression in the dilated myopathic heart may be
      correctable when a treatable cause is identified.

PMID- 1376917
TI  - Purification of a distinctive form of endotoxin-induced nitric oxide synthase
      from rat liver.
AB  - An endotoxin-induced form of nitric oxide synthase (EC 1.14.23) was purified to
      homogeneity from rat liver by sequential anion-exchange chromatography and
      affinity chromatography using 2',5'-ADP-Sepharose. The enzyme has a subunit
      molecular mass of 135 kDa as determined by SDS/PAGE, a maximum specific activity
      of 462 nmol of citrulline formed from arginine per min per mg, and a Km for
      arginine of 11 microM. The enzyme was strongly stimulated by the addition of
      calmodulin with an EC50 of 2 nM, but removal of free calcium from the assay
      medium only reduced activity by 15%. Calmodulin inhibitors significantly reduced
      the enzyme activity. Tetrahydrobiopterin, FAD, and FMN were all required for full
      enzyme activity. This form of endotoxin-induced nitric oxide synthase from liver
      differs from the inducible enzyme found in macrophages and is unusual in that it
      is stimulated by calmodulin with little dependence on the calcium ion
      concentration.

PMID- 1376918
TI  - Phosphorylation-dependent epitopes of neurofilament antibodies on tau protein and
      relationship with Alzheimer tau.
AB  - We have studied the phosphorylation of tau protein from Alzheimer paired helical
      filaments, of tau from normal human brain, and of recombinant tau isoforms. As a
      tool we used monoclonal antibodies against neurofilament protein [Sternberger,
      N., Sternberger, L. & Ulrich, J. (1985) Proc. Natl. Acad. Sci. USA 82, 4274-4276]
      that crossreact with tau in a phosphorylation-dependent manner. This allowed us
      to deduce the state of phosphorylation in normal and pathological tau, as well as
      antibody epitopes. The epitope of antibody SMI33 is at the first Lys-Ser-Pro
      sequence motif (residues 234-236) and requires an unphosphorylated Ser-235.
      Antibody SMI31 binds between Ser-396 (in the second Lys-Ser-Pro motif) and Ser
      404, both of which must be phosphorylated. SMI34 has a conformational epitope
      that depends on the interaction between regions on either side of the microtubule
      binding region; it also requires phosphorylation. The phosphorylatable serines
      detected by the SMI antibodies are part of Ser-Pro motifs and can be
      phosphorylated by a protein kinase activity that can be used to induce a paired
      helical filament-like state in human brain tau in vitro. The phosphates are
      incorporated in several stages that can be identified by antibody reactivity and
      gel shift. This suggests a role for the phosphorylation sites in Alzheimer
      disease, as well as the involvement of a Ser-Pro-directed protein kinase.

PMID- 1376919
TI  - A family of concanavalin A-binding peptides from a hexapeptide epitope library.
AB  - The lectin concanavalin A (Con A) binds methyl alpha-D-mannopyranoside (Me alpha
      Man) as well as alpha-D-mannosyl groups at the nonreducing terminus of
      oligosaccharides. Ligand peptides that mimic the binding of Me alpha Man to Con A
      were identified from screening an epitope library composed of filamentous phage
      displaying random hexapeptides. A consensus sequence was identified among
      affinity-purified phage; Con A binds phage bearing this sequence and is inhibited
      from doing so by Me alpha Man. When tested for binding against a panel of
      lectins, phage bearing this sequence bind only weakly to a closely related D
      mannose-binding lectin, indicating that binding to Con A is highly selective. A
      synthetic peptide bearing the consensus sequence blocks the precipitation of Con
      A by dextran with an inhibition strength equivalent to that of methyl alpha-D
      glucopyranoside. These results demonstrate that the specificity of Con A is not
      limited to carbohydrates and that highly selective sugar-mimics for lectins of
      plant, animal, or bacterial origin may be identified from epitope libraries.

PMID- 1376921
TI  - Random PCR mutagenesis screening of secreted proteins by direct expression in
      mammalian cells.
AB  - We have developed a general method for screening randomly mutagenized expression
      libraries in mammalian cells by using fluorescence-activated cell sorting (FACS).
      The cDNA sequence of a secreted protein is randomly mutagenized by PCR under
      conditions of reduced Taq polymerase fidelity. The mutated DNA is inserted into
      an expression vector encoding the membrane glycophospholipid anchor sequence of
      decay-accelerating factor (DAF) fused to the C terminus of the secreted protein.
      This results in expression of the protein on the cell surface in transiently
      transfected mammalian cells, which can then be screened by FACS. This method was
      used to isolate mutants in the kringle 1 (K1) domain of tissue plasminogen
      activator (t-PA) that would no longer be recognized by a specific monoclonal
      antibody (mAb387) that inhibits binding of t-PA to its clearance receptor. DNA
      sequence analysis of the mutants and localization of the mutated residues on a
      three-dimensional model of the K1 domain identified three key discontinuous amino
      acid residues that are essential for mAb387 binding. Mutants with changes in any
      of these three residues were found to have reduced binding to the t-PA receptor
      on human hepatoma HepG2 cells but to retain full clot lysis activity.

PMID- 1376920
TI  - Brief visual experience induces immediate early gene expression in the cat visual
      cortex.
AB  - Brief visual experience causes rapid physiological changes in the visual cortex
      during early postnatal development. A possible mediator of these effects is the
      immediate early genes whose protein products are involved in the rapid response
      of neurons to transsynaptic stimulation. Here we report evidence that the levels
      of immediate early gene mRNAs in the visual cortex can be altered by manipulating
      the visual environment. Specifically, we find that brief (1 h) visual experience
      in dark-reared cats causes dramatic transient inductions of egr1, c-fos, and junB
      mRNAs in the visual cortex but not in the frontal cortex. Levels of c-jun and c
      myc mRNAs are unaffected. These results suggest that select combinatorial
      interactions of immediate early gene proteins are an important step in the
      cascade of events through which visually elicited activity controls visual
      cortical development.

PMID- 1376922
TI  - Immunoelectron microscopic localization of the ubiquitin-activating enzyme E1 in
      HepG2 cells.
AB  - As the first enzyme in the ubiquitin system the ubiquitin-activating enzyme E1
      plays a pivotal role in all pathways of protein ubiquitination. In an effort to
      learn more about the cell biology of this pathway, we have purified the 110-kDa
      enzyme to homogeneity and generated a panel of distinct monoclonal antibodies to
      it. Using quantitative electron microscopic immunolocalization with these anti-E1
      monoclonal antibodies, we find that E1 is abundant both within the cytoplasm and
      nucleus. Within the cytoplasm, E1 was found throughout the cytoplasmic volume as
      well as enriched along the cytoplasmic face of the rough endoplasmic reticulum
      and associated with the dense material along the desmosomal junctions. E1 was
      also found associated with the cytoplasmic surface of endosomal/lysosomal
      vacuoles. Interestingly, E1 was also found within the mitochondria. The lumen of
      rough endoplasmic reticulum, Golgi complex, endosomes, and lysosomes were
      negative. The specific localization of E1 to distinct subcellular organelles
      suggests that E1 may play multiple physiological roles within the cell.

PMID- 1376923
TI  - A1 adenosine-receptor antagonists activate chloride efflux from cystic fibrosis
      cells.
AB  - A1 adenosine-receptor-antagonist drugs such as 8-cyclopentyl-1,3-dipropylxanthine
      (CPX) and xanthine amine congener (XAC) are found to activate the efflux of 36Cl-
      from CFPAC cells. These cells are a pancreatic adenocarcinoma cell line derived
      from a cystic fibrosis (CF) patient homozygous for the common mutation, deletion
      of Phe-508. The active concentrations for these compounds are in the low
      nanomolar range, consistent with action on A1 adenosine receptors. In addition,
      drug action can be blocked by exogenous agonists such as 2-chloroadenosine and
      also can be antagonized by removal of endogenous agonists by treatment with
      adenosine deaminase. Cells lacking the CF genotype and phenotype, such as HT-29
      and T84 colon carcinoma cell lines, appear to be resistant to activation of
      chloride efflux by either drug. CFPAC cells transfected with the CF transmembrane
      regulator gene, CFTR, are also resistant to activation by CPX. We conclude that,
      since these antagonists are of relatively low toxicity and appear to act somewhat
      selectively, they might be considered as promising therapeutic candidates for CF.

PMID- 1376925
TI  - Expression cloning of a cDNA from rabbit kidney cortex that induces a single
      transport system for cystine and dibasic and neutral amino acids.
AB  - We have isolated a cDNA clone by screening a rabbit kidney cortex cDNA library
      for expression of sodium-independent transport of L-arginine and L-alanine in
      Xenopus laevis oocytes. Expressed uptake relates to a single component of sodium
      independent transport for dibasic and neutral amino acids. This transport
      activity resembles the functionally defined system b0,+ and carries cystine and
      dibasic amino acids with high affinity. The rBAT (b0,+ amino acid transporter
      related) mRNA is found mainly in kidney and intestinal mucosa. It encodes a
      predicted 77.8-kDa protein with only one putative transmembrane domain and seven
      potential N-glycosylation sites. This protein could either be a constitutive
      element or a specific activator of system b0,+.

PMID- 1376924
TI  - Cloning of a rat kidney cDNA that stimulates dibasic and neutral amino acid
      transport and has sequence similarity to glucosidases.
AB  - The transport of amino acids across cell membranes is believed to be mediated by
      integral membrane proteins with distinct substrate specificities. Using
      expression cloning in Xenopus oocytes and assaying for the uptake of 14C-labeled
      cystine, we isolated a 2.3-kilobase cDNA (D2) from a rat kidney library. D2 is
      expressed specifically in kidney and intestine and induces the transport of both
      neutral and cationic amino acids. The deduced amino acid sequence predicts a 78
      kDa protein with a single transmembrane domain, a structure not typical of the
      known membrane transport proteins, which generally have multiple membrane
      spanning regions. The putative extracellular region is highly similar to the 4F2
      heavy-chain cell surface antigen and to a family of alpha-glucosidases, which
      raises the possibility that D2 encodes a transport activator or regulatory
      subunit.

PMID- 1376926
TI  - Stimulation of system y(+)-like amino acid transport by the heavy chain of human
      4F2 surface antigen in Xenopus laevis oocytes.
AB  - A kidney cortex cDNA clone (rBAT) has recently been isolated, which upon in vitro
      transcription and capping complementary RNA (cRNA) and injection into Xenopus
      laevis oocytes induces a system b0,(+)-like amino acid transport activity. This
      cDNA encodes a type II membrane glycoprotein that shows significant homology to
      another type II membrane glycoprotein, the heavy chain of the human and mouse 4F2
      surface antigen (4F2hc). Here we demonstrate that injection of human 4F2hc cRNA
      into oocytes results in the activation of a cation-preferring amino acid
      transport system that appears to be identical to the y(+)-like transport already
      present in the oocyte. This is based on the following results: (i) Injection of
      in vitro transcripts from 4F2hc cDNA (4F2hc cRNA) into oocytes stimulates up to
      10-fold the sodium-independent uptake of L-arginine and up to 4.1-fold the sodium
      dependent uptake of L-leucine. In contrast, 4F2hc cRNA does not increase the
      basal sodium-independent uptake of L-leucine. (ii) Basal and 4F2hc cRNA
      stimulated sodium-independent uptake of L-arginine is completely inhibited by L
      leucine in the presence of sodium. Similarly, the basal and 4F2hc cRNA-stimulated
      sodium-dependent uptake of L-leucine is entirely inhibited by L-arginine. (iii)
      The stimulation of sodium-independent uptake of L-arginine and the stimulation of
      sodium-dependent uptake of L-leucine induced by injection of 4F2hc cRNA are both
      completely inhibited by dibasic L amino acids and to a lesser extent by D
      ornithine. (iv) Both basal and 4F2hc cRNA-stimulated sodium-independent uptake of
      L-arginine show two additional characteristics of the system y+ transport
      activity: inhibition of L-arginine uptake by L-homoserine only in the presence of
      sodium and an increase in the inhibition exerted by L-histidine as the
      extracellular pH decreased. Our results allow us to propose that an additional
      family of type II membrane glycoproteins (composed by rBAT and 4F2hc) is involved
      in amino acid transport, either as specific activators or as components of amino
      acid transport systems.

PMID- 1376927
TI  - Sequence and molecular characterization of human monocyte/neutrophil elastase
      inhibitor.
AB  - cDNA encoding human monocyte/neutrophil elastase inhibitor (EI), a M(r)
      approximately 42,000 protein with serpin-like functional properties, has been
      sequenced. The 1316-base-pair sequence was obtained from overlapping clones and
      amplified DNA from libraries of monocyte-like and neutrophil-like cells.
      Hybridization with EI cDNA identified three EI mRNA species of 1.5, 1.9, and 2.6
      kilobases in U937 monocyte-like cells and no hybridizing mRNA in lymphoblastoid
      cells lacking detectable EI. The cDNA open reading frame encodes a 379-amino acid
      protein, of which 167 residues were confirmed by tryptic peptides. Although EI
      may function extracellularly as well as intracellularly, its deduced sequence
      lacks a typical cleavable N-terminal signal sequence. Sequence analysis
      established that EI is a member of the serpin superfamily. EI has greatest
      homology (50.1% identity of amino acids) with plasminogen activator inhibitor 2,
      also a monocyte protein, and ovalbumin and gene Y, which were previously grouped
      as an ancient branch of the serpin superfamily. The extent of EI identity with
      the functionally related serpin alpha 1 antitrypsin is only 30.1%. Sequence
      alignment indicates that the reactive center P1 residue is Cys-344, consistent
      with abrogation of elastase inhibitory activity by iodoacetamide and making EI a
      naturally occurring Cys-serpin. The cleavable bond, Cys-Met, suggests an
      oxidation-sensitive molecule capable of inhibiting more than one serine protease.
      Oxidation sensitivity would limit the place of action of EI to the immediate
      vicinity of carrier cells. The molecular structure will help clarify the likely
      role of EI in regulating protease action and preventing tissue damage by
      phagocytic cells.

PMID- 1376928
TI  - Predominant expression and activation-induced tyrosine phosphorylation of
      phospholipase C-gamma 2 in B lymphocytes.
AB  - The triggering of T- or B-cell antigen-specific receptors is accompanied by rapid
      tyrosine phosphorylation of distinct cellular substrates, one of which is the
      gamma 1 isoform of inositol phospholipid-specific phospholipase C (PLC-gamma 1).
      This phosphorylation event, mediated by a putative protein tyrosine kinase
      coupled to the antigen receptor, probably stimulates the enzymatic activity of
      PLC-gamma 1, thereby promoting inositol phospholipid hydrolysis and other
      downstream signal transduction events. Recently, another ubiquitously expressed
      PLC isoform, PLC-gamma 2 (which shares 50.2% amino acid homology with PLC-gamma
      1), has been identified. PLC-gamma 2-specific antibodies were used to evaluate
      the distribution and potential signaling role of this isoform in lymphocytes.
      Here, we report that, in contrast to T lymphocytes that express predominantly PLC
      gamma 1, the major isoform expressed in murine and human resting B cells is PLC
      gamma 2. Among B-cell tumor lines, all five murine B-lymphoma lines tested and
      one of six human B-lymphoblastoid cell lines also expressed predominantly PLC
      gamma 2. However, three other human lines preferentially expressed PLC-gamma 1,
      and two others displayed similar levels of the two PLC-gamma isoforms.
      Furthermore, the triggering of B-cell surface immunoglobulin by anti-receptor
      antibodies was accompanied by a rapid tyrosine phosphorylation of PLC-gamma 2,
      which peaked after 5 min of stimulation. Conversely, and in agreement with recent
      reports, triggering of the T-cell antigen receptor complex led to the predominant
      phosphorylation of PLC-gamma 1 on tyrosine. These findings identify PLC-gamma 2
      as a substrate for a B-cell putative protein tyrosine kinase coupled to the
      antigen receptor and suggest that its tyrosine phosphorylation constitutes a
      critical and early event in B-cell activation and, furthermore, that PLC-gamma 1
      and PLC-gamma 2 may participate in similar but distinct signal transduction
      pathways in lymphocytes.

PMID- 1376930
TI  - Effect of the calcium channel blockers cinnarizine and flunarizine on gastric
      histamine content in rats with experimentally-induced ulcers.

PMID- 1376931
TI  - Presenting a routine screening test in antenatal care: practice observed.
AB  - People's knowledge of screening tests for which they are eligible and which they
      may have undergone is frequently low. The aim of the current study is to
      determine the extent to which this is due to how a test is offered and explained.
      Routine consultations (n = 102) between midwives, obstetricians and pregnant
      women were tape-recorded to determine how a routine screening test for fetal
      abnormalities (maternal serum alpha-fetoprotein) is presented. The test was
      presented in the vast majority of consultations. Overall, little information was
      provided about the test, the conditions screened for, and the meaning of either a
      positive or a negative result. Screening was presented in such a way as to
      encourage women to undergo the test. The way in which routine prenatal screening
      is presented is unlikely to maximise informed decisions about whether to
      participate in this screening programme. Factors likely to be influencing test
      presentation include knowledge, attitudes and skills of staff, as well as the
      attitudes of pregnant women. The results of this study highlight a need to train
      the heath professionals implementing screening programmes in how to inform people
      fully about low probability but serious events without alarming them unduly, or
      reassuring them falsely.

PMID- 1376929
TI  - Expression cloning of the murine and human interleukin 9 receptor cDNAs.
AB  - Interleukin 9 (IL-9) is a T-cell-derived lymphokine that induces the
      proliferation of various lymphoid and hemopoietic cells. A cDNA clone encoding
      the murine IL-9 receptor was isolated by expression cloning in COS cells and
      screening with 125I-labeled IL-9. Transient expression of this cDNA produced high
      affinity binding sites for IL-9. The predicted 52-kDa protein contains a putative
      signal peptide and a typical transmembrane domain. A cDNA for the human homologue
      was isolated by cross-hybridization. Transfection of this cDNA in a murine T-cell
      clone conferred responsiveness to human IL-9. Sequence analysis revealed that the
      IL-9 receptor belongs to the recently described hematopoietin receptor super
      family and is expressed in membrane-bound and soluble forms.

PMID- 1376932
TI  - Percutaneous drainage of 335 consecutive abscesses: results of primary drainage
      with 1-year follow-up.
AB  - Retrospective review of percutaneous abscess drainage (PAD) of 335 abscesses in
      323 consecutive patients was undertaken. Particular attention was directed to
      body location, associated organ system, communications and fistulae, and to the
      underlying immunologic status of the patient. One-year follow-up was available in
      all patients. Overall, the cure rate was 62.4% (209 of 335 abscesses), with a
      failure rate of 8.95% (30 of 335 abscesses). There were 14.2% (46 of 323
      patients) deaths in the follow-up period, of which 4.6% (15 of 323 patients) were
      believed attributable to sepsis or septic complications. The overall complication
      rate was 9.8% (33 of 335 abscesses), most of which were minor in nature. For the
      patient exhibiting immunocompromise, representing 53.1% (172 of 323 patients) of
      the patient population, the cure rate was 53.4% (95 of 178 abscesses), which was
      significantly lower than the cure rate of 72.6% (114 of 157 abscesses) for the
      immunocompetent patient population (n = 151) (P less than .001). The recurrence
      rate was 2.1% (seven of 335 abscesses), with all recurrences within 3 months of
      initial drainage. PAD is effective and permanent treatment for both
      immunocompromised and immunocompetent patients.

PMID- 1376933
TI  - Localized prostate cancer: use of serial prostate-specific antigen measurements
      during radiation therapy.
AB  - The serum half-life of prostate-specific antigen (PSA) after radical
      prostatectomy is about 3 days; to the authors' knowledge, the PSA half-life
      during radiation therapy (RT) has not been investigated with weekly serial
      measurements. To determine the rate of decline and the half-life of PSA, serial
      measurements were obtained during 6-8 weeks of external-beam RT for localized
      prostate cancer. PSA values were determined immediately before and approximately
      24 hours after the first dose of RT; thereafter, weekly measurements were made.
      There was a downward trend in PSA levels in 19 patients, with a median half-life
      of 58.5 days; the mean decline was 1.6% per day. However, in four patients, PSA
      levels either rose and fell to pre-RT values or increased steadily. The effect of
      digital rectal examination (DRE) on PSA levels was also analyzed. When the dates
      of DRE and subsequent PSA levels were inspected, no increase in PSA levels
      subsequent to DRE was found, although three of the four patients in whom PSA
      levels did not decrease underwent multiple DREs. The authors found a
      statistically significant (P = .023) transient elevation in the mean PSA values
      after the first fraction of RT (2 Gy) was administered; the mechanism and
      importance of which are not known.

PMID- 1376934
TI  - Relative abundance of human placental phospholipase A2 messenger RNA in late
      pregnancy.
AB  - The aim of this study was to determine messenger RNA (mRNA) levels for a specific
      phospholipase A2 (PLA2) in human placenta during late gestation prior to the
      onset of labour. The relative abundance of human placental mRNA for a
      nonpancreatic Group II PLA2 was determined using cDNA clone specific for this
      PLA2. Twenty seven placentae were collected from women undergoing elective (i.e.
      before the onset of labour) Caesarean section between 37 and 41 completed weeks
      gestation. The relative amount of human placental PLA2 mRNA did not change
      significantly over this period of late pregnancy (p greater than 0.8).
      Previously, we have demonstrated that placental PLA2 messenger RNA levels are
      increased in association with spontaneous onset labour at term in the human. The
      data obtained in this current study are consistent with the conclusion that the
      regulation of this human placental PLA2 gene is tightly controlled around the
      time of parturition and that its expression is increased acutely in association
      with labour.

PMID- 1376935
TI  - Serum prostate-specific antigen in monitoring the response of carcinoma of the
      prostate to radiation therapy.
AB  - In order to assess the value of serum prostate-specific antigen (PSA) levels in
      the monitoring of patients with localized prostatic carcinoma undergoing radical
      radiation therapy, 146 previously untreated patients were entered into this
      study. Sixty to 70 Gy were administered to the prostate over 8 to 9 weeks. Serum
      PSA levels were measured prior to radiotherapy, every 3 months during the first
      year and every 6 months thereafter. Median follow-up was 28 months. Pretreatment
      PSA values exceeded 10 ng/ml in 62% (91/146). Initial PSA values were correlated
      with tumor size and Gleason score. Six months after completion of radiation
      therapy, PSA levels decreased as compared to initial value in 88.3% of the
      patients. It had fallen to 10 ng/ml or less in 54 (59%) out of the 91 patients
      with initial abnormal PSA levels. Patients whose initial PSA exceeded 50 ng/ml
      attained levels of 10 ng/ml or less in only 19% of the cases (6/32). Only 3 of
      the 55 patients (5.5%) with both initial and 6-month PSA values less than or
      equal to 10 ng/ml developed metastasis. Out of the 91 patients with initial PSA
      values over 10 ng/ml, 54 (59.6%) had a 6-month PSA level of 10 ng/ml or less, and
      only 4/54 (7.4%) relapsed. By contrast, 13 of the 37 patients (35.1%) with a 6
      month PSA value persistently above 10 ng/ml relapsed. The 3-year relapse-free
      survival is 85.1% for patients with a 6-month PSA level less than or equal to 10
      ng/ml, and 50.2% for patients with persistently elevated PSA values.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1376936
TI  - [Stress and nursing. Comparison of the levels of burnout between surgical
      departments and intensive care units].
AB  - Burnout is a state of workers of helping professions that results from a
      situation of work stress and is characterised by emotional exhaustion,
      depersonalization and low personal accomplishment. Burnout levels were measured
      in three nursing staffs: two of them working in intensive care units and one in a
      surgical department. The results show significant statistical differences between
      the two staffs of intensive care units. Such differences seem to be connected
      with the psychological climate evaluated in the units.

PMID- 1376937
TI  - [Role of interferon in the treatment of renal cancer in adults].
AB  - Alpha interferon is effective in the treatment of metastatic renal cell cancer.
      To obtain a maximal efficacy, alpha interferon should be used at a dose of 10
      MU/m2, or 18 MU total dose, given daily or three times a week. At such doses
      interferon produces flu-like symptoms and severe asthenia and thus should be
      proposed only to patients who have a good performance status. The response rate
      is low, in the order of 15-20%, and the median remission duration is short (6-10
      months). However a few patients experience very durable remissions, sometimes for
      more than 5 years. The response rate may possibly be improved to 20% to 35% by
      combining interferon alpha with antineoplastic agents or to other cytokines,
      namely interleukin 2. Finally because of its supposed mechanisms of action-direct
      tumor growth inhibition and enhancement of the host's immune defenses--interferon
      may be of benefit in the adjuvant setting.

PMID- 1376938
TI  - Molecular determinants of growth, angiogenesis, and metastases in breast cancer.

PMID- 1376939
TI  - [The manifestations of seropositivity].

PMID- 1376940
TI  - Prolonged excretion by heifers of an inappropriately used intramammary
      antibiotic.

PMID- 1376941
TI  - Incidence of atypical bronchioloalveolar cell hyperplasia of the lung: relation
      to histological subtypes of lung cancer.
AB  - The incidence of atypical bronchioloalveolar cell hyperplasia (ABH) of the lung
      was investigated to evaluate the possibility of this lesion being a precancerous
      stage in the histogenesis of adneocarcinoma. Lobectomy and pneumonectomy
      specimens of 165 primary and 45 metastatic tumour cases were step-sectioned
      horizontally and examined histologically. An average of 51 blocks were taken in
      each case. Sixty-seven ABHs up to 10 mm in diameter were detected, only 2 lesions
      being associated with scar tissue. Age was one factor apparently related to ABH
      development, although not the major one. There was no correlation between smoking
      index and ABH occurrence. In males, the incidence was highest in association with
      adenocarcinoma (25.5% of cases, 0.8% of sections), followed by large cell
      carcinoma (25.0% of cases), squamous cell carcinoma (10.5% of cases) and
      metastatic tumours from other sites (4.8% of cases). In females, ABH was also
      more common together with adenocarcinoma (8.3% of cases) than with metastatic
      tumours (4.0% of cases). The differences in male incidences by case and by
      section between the adenocarcinoma and metastatic tumour categories were
      statistically significant (P less than 0.05, P less than 0.01 respectively)
      indicating that ABH may be a precancerous lesion capable of transformation of
      adenocarcinoma.

PMID- 1376942
TI  - The distribution of factor XIIIa-positive cells in the human fetus and placenta.
AB  - Immunohistochemical staining for factor XIIIa, a transglutaminase, revealed a
      variety of positively stained cells in human fetal tissues. Factor XIIIa-positive
      cells were most numerous in the dermis and connective tissues. Numerous large,
      stellate cells in placental villi, decidua, and chorionic membranes also
      expressed factor XIIIa at 7-9 weeks gestational age, before the onset of fetal
      hematopoiesis. There was heterogeneity in the staining for factor XIIIa in the
      early and late fetal tissues, in both rounded and in dendritic cells. In
      preparations of consecutive sections and in double-labelling experiments, some
      cells expressed both factor XIIIa and certain monocyte markers and were
      identified in close association with blood vessels and lymphoid organs in the
      late fetus and in the placental villi at the end of gestation. Other rounded and
      dendritic cells expressed factor XIIIa but not monocyte markers, and were found
      in adult and fetal connective tissues at all gestational ages. These results
      suggest that there are two factor XIIIa-positive cell populations. One population
      is present at all developmental stages, does not express monocyte markers, and
      probably differentiates in situ from primitive mesenchyme. The other population
      appears mainly after the onset of fetal hematopoiesis, coexpresses some monocyte
      markers, is HLA-DR positive and may be capable of antigen presentation.

PMID- 1376943
TI  - Electron microscopic study of paired helical filaments and cerebral amyloid using
      a novel en bloc silver staining method.
AB  - A one step en bloc silver staining method which was originally established to
      study nucleolar organizer regions has been applied for the demonstration of both
      paired helical filaments (PHF) and extracellular cerebral amyloids in semi-thin
      sections and at the electron microscopic level. The three forms of PHF can be
      visualized: (1) neurofibrillary tangles are shown in all stages from first
      appearance in form of intracellular patches of PHF to severely degenerated shadow
      like "ghost" tangles; (2) neuropil threads are distinctly stained in great
      numbers; and (3) PHF are easily detected as neuritic components in amyloid
      plaques. All forms of fibrillar extracellular amyloid structures, i.e. "diffuse",
      "classical" and "burnt out" plaques, are well demonstrated; congophilic
      angiopathy reveals amyloid preferentially in arteries and arterioles of the
      leptomeninges and cortex ranging from small circumscribed patches to large
      circumferential amounts with occasional plaque-like condensations or broad loose
      accumulations of amyloid; perivascular cuffs and laminar subpial deposits of
      amyloid are stained as well. At the electron microscopic level all lesions are
      clearly visible in non uranyl/lead-stained specimens, characterized by varying
      numbers of silver grains on a pale background. The detailed demonstration of
      structures in archival material, which had been stored in paraffin and re
      embedded for electron microscopy, is due to the demonstration of argyrophilic
      structures by the protective colloidal developer of gelatin and formic acid and
      to the proteolytic resistance of insoluble PHF and extracellular amyloids in
      plaques and congophilic angiopathy.

PMID- 1376944
TI  - Paraffin section immunohistochemistry in the diagnosis of Hodgkin's disease and
      anaplastic large cell (CD30+) lymphomas.
AB  - Morphological and immunohistological studies were carried out on a series of 137
      lymphomas including CD30+ anaplastic large cell (ALC) lymphomas (48 cases) and
      non-lymphocyte predominant Hodgkin's disease (HD) (89 cases), with the aim of
      assessing in situ expression of a combination of antibodies including anti
      CD30/BerH2, epithelial membrane antigen (EMA), CD15 and CD45, in addition to
      other monoclonal antibodies suitable for paraffin tissues. A greater proportion
      of cases of ALC lymphomas than of HD exhibited positivity for CD45 (91.7% vs
      17.6%), EMA (56.2% vs 4.5%), CD43 (53.6% vs 13.1%) and CD45RO (39.5% vs 3.5%),
      whereas Reed-Sternberg (RS) cells in HD most frequently expressed CD15 (93.2% vs
      20.8%) antigen. Moreover, in 35 of 48 (72.9%) ALC lymphomas tumour cells
      expressed the CD30+, CD45+, CD15-, EMA- or + phenotypic profile, while in the
      same percentage (62/85) of HD cases RS cells were found to express the CD30+,
      CD45-, CD15+, EMA- profile. This study suggests that the differential expression
      of CD45, EMA, and CD15 may be used in the separation of ALC lymphomas and HD.
      However, co-expression of CD30, CD45 and CD15 antigens by RS cells in HD (14/85
      cases, 16.5% in this series) and by tumour cells in ALC lymphomas (9/48 cases,
      18.7% in this series) may be encountered in a non-negligible fraction of cases.

PMID- 1376945
TI  - Estimates from two survey designs: national hospital discharge survey.
AB  - The methodology for the National Hospital Discharge Survey (NHDS) has been
      revised in several ways. These revisions, which were implemented for the 1988
      NHDS, included adoption of a different hospital sampling frame, changes in the
      sampling design (in particular the implementation of a three-stage design),
      increased use of data purchased from abstracting service organizations, and
      adjustments to the estimation procedures used to derive the national estimates.
      To investigate the effects of these revisions on the estimates of hospital use
      from the NHDS, data were collected from January through March of 1988 using both
      the old and the new survey methods. This study compared estimates based on the
      old and the new survey methods for a variety of hospital and patient
      characteristics. Although few estimates were identical across survey
      methodologies, most of the variations could be attributed to sampling error.
      Estimates from two different samples of the same population would be expected to
      vary by chance even if precisely the same methods were used to collect and
      process the data. Because probability samples were used for the old and new
      survey methodologies, sampling error could be measured. Approximate relative
      standard errors were calculated for the estimates using the old and new survey
      methods. Taking these errors into account, less than 10 percent of the estimates
      were found to differ across survey methodologies at the 0.05 level of
      significance. Because a large number of comparisons were made, 5 percent of the
      estimates could have been found to be significantly different by chance alone.
      When there were statistically significant differences in nonmedical data, the new
      methods appeared to produce more accurate estimates than the old methods did.
      Race was more likely to be reported using the new methods. "New" estimates for
      hospitals in the West Region and government-owned hospitals were more similar
      than the corresponding "old" estimates to data from the census of hospitals
      conducted by the American Hospital Association. The numerous significant
      differences in estimates for bed size categories between the two survey
      methodologies reflected the change in the universe and definition of beds for the
      new survey. Few statistically significant differences were found in the medical
      data using the old and the new survey methods. Two main differences, in estimates
      for cataract and alcohol dependence syndrome, may have resulted from problems
      with the new survey. A measurement error, reporting outpatients to the NHDS, is
      one possible explanation of the higher estimates for diagnosis of cataract using
      the new survey methods.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1376946
TI  - National hospital discharge survey.
AB  - This report presents statistics on the utilization of non-Federal short-stay
      hospitals based on data collected through the National Hospital Discharge Survey
      from a national sample of the hospital records of discharged inpatients.
      Estimates are provided by the demographic characteristics of patients discharged,
      geographic region of hospitals, conditions diagnosed, and surgical and
      nonsurgical procedures performed. Measurements of hospital use include frequency,
      rate and percent of discharges and days of care, and average length of stay.

PMID- 1376947
TI  - Influence of the cryoprotective agents glycerol and hydroxyethyl starch on red
      blood cell ATP and 2,3-diphosphoglyceric acid levels.
AB  - Because hydroxyethyl starch (HAES) is used for volume replacement therapy and as
      a cryoprotectant for frozen red blood cells (RBCs), this compound, in contrast to
      glycerol, does not require labor-intensive removal from thawed cells prior to
      transfusion. We here report the effect of both glycerol and HAES on the RBC
      organic phosphates ATP and 2,3-diphosphoglyceric acid (2,3-DPG). The CPD-A1
      stabilized RBCs of 20 healthy donors (3 females, 17 males) were separately frozen
      in either 40% glycerol or 6% HAES, of molecular weight 200,000. ATP and 2,3-DPG
      concentrations were determined in CPD-A1 RBCs before addition of cryoprotectant
      and in cryopreserved thawed RBCs after 24 h storage at -80 degrees C (glycerol)
      and -196 degrees C (HAES). It appears that HAES, but not glycerol, significantly
      reduces ATP concentrations whereas both lead to a reduction of 2,3-DPG
      concentrations; this reduction was more pronounced with glycerol than with HAES.
      Experiments with the blood of 6 donors demonstrated that HAES affects
      autohemolysis by 16%, in contrast to glycerol, after which cryoprotectant
      autohemolysis was affected by 3.1% only. RBC recoveries were comparable using
      glycerol or HAES as cryoprotectants. A distinct pattern of reduction of 2,3-DPG
      levels by glycerol and less by HAES, and of ATP levels by HAES but not by
      glycerol, emerges. Our findings may be of importance if HAES is to be introduced
      as a convenient cryoprotectant.

PMID- 1376948
TI  - Evaluation of four different methods for platelet freezing. In vitro and in vivo
      studies.
AB  - This report describes our experience with various techniques for the freezing of
      platelet-rich plasma, removed from the final product after leukapheresis
      procedures performed on 14 hematological patients. A total of 194 platelet units
      were frozen for subsequent autologous transfusion, by the following four methods:
      (1) 6% dimethyl sulfoxide (DMSO); (2) a combination of 5% DMSO/6% hydroxyethyl
      starch; (3) 3% glycerol; (4) 5% glycerol/4% glucose. Each technique was evaluated
      by measuring the percentage of platelet recovery, malondialdehyde (MDA)
      production, and lactate dehydrogenase release. To investigate the safety and
      therapeutic effectiveness of the previously frozen platelets, in vivo comparison
      of four platelet freezing methods was made in 8 thrombocytopenic patients, using
      corrected platelet increment (CCI), determined at 24 h. Our in vitro results
      indicate that the cryopreservation with 6% DMSO, without controlled cooling rate,
      provides significantly (p less than 0.05) greater platelet recovery (75%) as
      compared to other systems. The decrease of MDA production and the increase in
      plasma lactate measured after the thawing process was less in the DMSO-frozen
      units than in the other platelet units. When platelets, cryopreserved by this
      method, were subsequently transfused into patients, a significantly better CCI
      (greater than 5,000/microliters) was obtained. In our series, 6 patients were
      entirely supported with frozen autologous platelets. It appears from this study
      that a better understanding of the physical and biochemical events occurring
      during the freezing process will improve platelet cryopreservation, allowing a
      more systematic use of frozen platelets in the support of thrombocytopenic
      patients.

PMID- 1376949
TI  - [Tubal rupture after prostaglandin instillation despite decreasing beta-HCG
      values].
AB  - Over the past years laparoscopic surgery has become widely accepted in the
      treatment of tubal pregnancy and instillation of prostaglandin is well
      established. However, the failure rate is around 20%. This report describes a
      case of tubal pregnancy treated according to this procedure where the therapy
      initially seemed to be successful. Instillation of prostaglandin F2 alpha was
      followed by decreasing beta-HCG values, which continued to decrease after
      discharge. Thus, rupture of the operated tube on day 17 after surgery was
      completely unexpected.

PMID- 1376951
TI  - Protection from herpes simplex virus type 2 is associated with T cells involved
      in delayed type hypersensitivity that recognize glycosylation-related epitopes on
      glycoprotein D.
AB  - Immunization of mice with a vaccinia recombinant (VP176) that expresses a fully
      glycosylated herpes simplex virus (HSV) glycoprotein D (gD) induces long-term
      (greater than or equal to 50 days) HSV-specific lymphoproliferation and delayed
      type hypersensitivity (DTH) responses, the ability to eliminate a high challenge
      dose of HSV-2 from the epidermis and protection from fatal disease due to HSV
      replication in the nervous system. Adoptive transfer studies indicate that
      protection is mediated by the DTH functions of L3T4+ cells and requires the
      contribution of a non-specific irradiation-sensitive cell. Long-term protection
      (defined as that seen at greater than or equal to 50 days after immunization)
      from fatal HSV-2 challenge, virus clearance from the epidermis, and HSV-specific
      T-cell responses are not induced by a partially glycosylated gD expressed by a
      vaccinia recombinant (VP254) in which gD is controlled by a late vaccinia virus
      promoter. However, mice immunized with VP254 are protected from HSV-2 challenge
      early (day 10) after immunization. The VP254-induced protection is HSV-specific,
      but it is not mediated by L3T4+ and Lyt2+ cells. The findings are discussed
      within the context of future developments of anti-HSV vaccines.

PMID- 1376952
TI  - A hospice for Calgary: should the government fund it?

PMID- 1376950
TI  - [Diagnosis of chronic pancreatitis. Studies of duodenal juice after stimulation
      with the secretin-ceruletide test. Decision limits and evaluation of various
      parameters].
AB  - 187 patients were checked up over 4 years by the secretin-ceruletide test.
      Independently of the test results they were assigned to various disease groups on
      the basis of clinical assessment. 131 subjects were divided in a pilot
      investigation into: subjects with a healthy pancreas (n = 55); subjects with
      chronic pancreatitis (n = 50); subjects whose pancreatic condition could not be
      classified clearly (n = 26). 8 parameters were compared by univariate and
      multivariate statistical procedures in order to confirm or rule out the presence
      of chronic pancreatitis. The discriminatory power of the following parameters in
      duodenal fluid proved to be sufficiently high, with less than 15% frequency of
      misclassification: chymotrypsin (activity) and/or; lipase (activity) and/or;
      amylase (activity); viscosity. Under routine conditions measurement of the
      activity of two of these enzymes is sufficient. Their contribution to
      discrimination proved to be approximately equal. The diagnostic sensitivity and
      specificity of the parameters bicarbonate, lipase (concentration), trypsin
      (activity) and volume of duodenal fluid are lower. The classification rules
      derived from the above pilot group were confirmed by a diagnostic study under
      routine condition in a test group of 38 patients. Limitation to examining only
      volume and a maximum of 3 parameters which proved best in distinguishing between
      patients with chronic pancreatitis and healthy subjects, together with the
      omission of the first-hour samples after a secretin bolus, considerably reduced
      laboratory workload without altering the discriminatory power of the secretin
      ceruletide test.

PMID- 1376953
TI  - Heterotopic pancreas of the stomach. Histogenesis and immunohistochemistry.
AB  - Ordinary histological investigation has suggested that heterotopic pancreas of
      the stomach may have two types of histogenesis; one is development from
      immigrated fetal pancreas tissue, and the other is development from primitive
      gastric mucosal epithelium following penetration into the submucosa with
      subsequent erroneous differentiation into pancreas tissue. It is suspected that
      type-I lesions include the majority of cases caused by immigration from fetal
      pancreas, and that some type-II cases arise through erroneous differentiation of
      primitive gastric mucosal epithelium. With regard to immunohistochemical
      findings, cells positive for pancreatic polypeptide and amylase were much more
      numerous in the acini of type-I cases compared with type-II cases. Positive cells
      were found not infrequently in the acini of type-II cases after staining for
      pancreatic polypeptide, insulin, glucagon, somatostatin, serotonin, and gastrin.
      On the other hand, a small number of cells in islets were not infrequently
      positive for alpha 1-antitrypsin, alpha 1-antichymotrypsin, and amylase. It is
      considered that in the heterotopic pancreas, ductal cells have the potential to
      differentiate into acinar cells and islet cells, as is the cases in the
      orthotopic pancreas.

PMID- 1376954
TI  - Establishment of a human hepatoblastoma model in athymic nude mice. Producibility
      of fatty acid-binding protein, alpha-fetoprotein, and alpha 1-acid glycoprotein.
AB  - An athymic nude mouse model of human hepatoblastoma, designated HBL-2, was
      established. HBL-2 produced alpha-fetoprotein (AFP) and the serum level in tumor
      bearing mouse was roughly proportional to the tumor weight. Reactivity of AFP to
      Concanavalin A and Lens culinaris lectins indicated that it contained
      predominantly fucosylated, non-bisecting N-acetylglucosamine as a sugar moiety.
      Alpha 1-acid glycoprotein (AAG) was also found in both HBL-2 tumor extract and
      sera of tumor-bearing mice. The serum level, however, was not proportional to
      either the tumor weight or the value of the tumor extract. In addition, fatty
      acid-binding protein (FABP) was detected in approximately 40% of tumor cells and
      in tumor extract with polyclonal antibody against liver FABP. Thus, HBL-2 is an
      unique model of human hepatoblastoma, in that it produces FABP in addition to AAG
      and AFP.

PMID- 1376955
TI  - Some observations on the localization of hyaluronic acid in adult, newborn and
      embryonal rat brain.
AB  - Hyaluronic acid was localized in acetone-fixed cryostat sections of brain and
      spinal cord obtained from adult, newborn and embryonal rat. The sections were
      incubated with glial hyaluronate-binding protein (GHAP) of human origin and the
      protein was visualized by indirect immunofluorescence with monoclonal antibodies
      raised to human GHAP and not staining rat brain by immunofluorescence. GHAP is a
      brain extracellular matrix (ECM) glycoprotein, approximately 60,000 molecular
      weight, which is structurally related to the HA-binding region of cartilage ECM
      proteins. The distribution of hyaluronate in adult brain white matter and
      cerebellar cortex was similar to that previously reported for GHAP. In both
      cases, the reaction product formed a mesh surrounding myelinated axons and
      granule cells. Hyaluronate was also found in parts of the brain that did not
      contain GHAP. A finely reticulated mesh was observed in the neuropil between cell
      bodies in cerebral cortex and basal ganglia. Scattered cortical neurons were
      surrounded by a rim of reactive material. Perineural staining was the rule rather
      than the exception in spinal cord anterior horn motoneurons, inferior olivary
      nucleus, large bulbar reticular neurons and dentate nucleus of cerebellum. The
      only part of the brain which appeared relatively free of hyaluronate was the
      molecular layer of the cerebellum. In newborn and embryonal rat, the densely
      packed cell bodies in cerebral gray matter, periventricular germinal layer and
      external granular layer of cerebellum were surrounded by hyaluronate. Small
      droplets of hyaluronate were observed in between the cylindrical epithelial cells
      lining the neural tube in 11 day embryos. Non-myelinated fiber tracts and the
      molecular layer of the developing cerebellum were relatively unstained. No
      hyaluronate was detected in the ependyma lining the cerebral ventricles and the
      central canal of the spinal cord.

PMID- 1376956
TI  - The structural and neurochemical development of the fetal guinea pig retina and
      optic nerve in experimental growth retardation.
AB  - In this study we have examined structural and neurochemical aspects of retinal
      and optic nerve development in experimentally growth-retarded fetal guinea pigs
      following maternal unilateral artery ligation. Eye weight (n = 4) and total
      retinal area (n = 6) at 62 days gestation (term approximately 66 days) were both
      relatively spared when expressed as a percentage of body weight but in absolute
      terms were significantly reduced by 18% (P less than 0.001) and 13% (P less than
      0.05) respectively when compared with age-matched controls. The numerical density
      of neurons in the ganglion cell layer was significantly higher at both 52 days (n
      = 4) and 62 days (n = 4) in growth-retarded fetuses compared with controls.
      However, there was no difference between the groups in the total number of
      neurons in this retinal layer at either age, since retinal areas are reduced in
      growth retardation. The area of neuronal somata in the ganglion and inner nuclear
      layers was significantly reduced in growth-retarded fetuses compared with
      controls. There was a concomitant reduction in the width of the cellular layers
      in the retina and also in the plexiform (synaptic) and photoreceptor layers. The
      growth of the outer segments of the photoreceptor layer was particularly affected
      in peripheral retina. The higher packing density of cells and the reduced growth
      of the plexiform layers suggests a reduction in the growth of the neuropile in
      growth-retarded fetuses compared with controls. The radial bundling of ganglion
      cell axons coursing across the retina to enter the optic nerve head was poorly
      defined in growth retardation. In addition myelination was delayed in the optic
      nerve with the numerical density of myelinated axons being significantly reduced
      (P less than 0.005) in growth-retarded fetuses compared with controls. There was
      a significant reduction (P less than 0.01) in the number of amacrine cells in the
      inner plexiform layer expressing Substance P-like immunoreactivity in growth
      retarded fetuses compared with controls. Glutamate-like immunoreactivity was most
      intense in the five laminae of the inner plexiform layer and in the outer
      plexiform layer and less pronounced in photoreceptors, ganglion cells and their
      axons. There was no qualitative difference in glutamate immunoreactivity between
      control and growth-retarded fetuses in any of these structures. Thus we have
      shown that intrauterine growth retardation has specific effects on the
      development of the fetal guinea pig retina, reducing the growth of several types
      of neurons and their processes and affecting the expression of the neuropeptide
      substance-P in amacrine cells.

PMID- 1376957
TI  - Identification of a functional mononuclear precursor of the osteoclast in chicken
      medullary bone marrow cultures.
AB  - Mononuclear cells were isolated from the peritrabecular bone marrow from the
      medullary bone of laying hens maintained on a calcium-deficient diet for 1 week.
      These cells were cultured for up to 7 days on devitalized bovine bone slices
      after removing the nonadherent fraction. The mononuclear precursors of the
      osteoclast that are present in such cultures adhere to bone matrix. These cells
      are TRAP+, express the vitronectin receptor at high levels, and also express high
      levels of sodium pumps and of carbonic anhydrase, enzymes that are
      characteristically enriched in the mature osteoclast. Finally, the most mature
      mononuclear precursors were found to be capable of resorbing the extracellular
      bone matrix before forming multinucleated osteoclasts.

PMID- 1376959
TI  - The role of histamine on the control of thyrotropin secretion in rats.
AB  - The presence of histamine (HA) in the hypothalamus, especially in its median
      eminence, as well as results of previous studies from this laboratory, suggest a
      participation of this amine in the regulation of TSH (thyroid stimulating
      hormone, thyrotropin) secretion. In the present investigation, rats were treated
      with a single injection of cimetidine (CIM - 100 mg/kg ip), an H2-HA receptor
      antagonist. In vitro release of TSH in response to hypothalamic extracts from
      control animals, was approximately 20% smaller when evoked from pituitaries
      obtained from CIM-treated, rather than control animals. The addition of
      hypothalamic extracts from CIM-treated rats to incubates of pituitaries from
      either control or CIM treated rats did not significantly change basal TSH
      secretion, suggesting that TRH (thyrotropin releasing hormone) content was
      decreased by the anti-histamine treatment. These results point towards a
      facilitatory role of HA on TSH secretion both at the hypothalamic level where it
      may interfere with TRH synthesis, as well as at the pituitary level where it may
      modify TSH response to TRH.

PMID- 1376960
TI  - Microorganisms and mediator release: new aspects in airway diseases.

PMID- 1376958
TI  - Dietary restriction of calcium, phosphorus, and vitamin D elicits differential
      regulation of the mRNAs for avian intestinal calbindin-D28k and the 1,25
      dihydroxyvitamin D3 receptor.
AB  - We investigated the regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-induced
      calbindin-D28k (CaBP) and of the vitamin D receptor (VDR) by evaluating CaBP
      protein, CaBP mRNA, and VDR mRNA under conditions of altered intake of vitamin D,
      calcium, or phosphorus. Chickens were maintained for 10 days on one of four
      diets: vitamin D-deficient, normal (1.0% Ca and 1.1% P), low calcium (0.1% Ca and
      1.2% P), and low phosphorus (1.1% Ca and 0.3% P). CaBP was undetectable in D
      deficient duodena and was elevated above normal values by low-calcium (3.1-fold)
      and low-phosphorus (2.3-fold) intake. Contradictory to published data, we
      observed a correlation between CaBP protein and mRNA levels in that the CaBP mRNA
      was absent in D-deficient intestine and augmented threefold and twofold in low
      calcium and low-phosphate duodena, respectively. In contrast, VDR mRNA
      concentrations were identical in vitamin D-deficient and normal duodena, implying
      that intestinal VDR is not dependent upon 1,25-(OH)2D3 for basal expression.
      Chickens fed a low-phosphorus diet displayed a twofold increase in VDR mRNA, but
      those fed a low-calcium diet exhibited a dramatic decrease in VDR mRNA. These
      data show that CaBP mRNA and protein levels are modulated in a tightly coupled
      fashion, and they are consistent with previous conclusions that augmented
      circulating 1,25-(OH)2D3 stimulates CaBP expression when dietary calcium or
      phosphorus is limiting. However, a more complex regulation of VDR expression
      occurs in that low-phosphorus restriction enhances VDR mRNA levels, possibly via
      increased circulating 1,25-(OH)2D3. Conversely, reduced dietary calcium
      diminishes VDR mRNA despite increased circulating 1,25-(OH)2D3, indicating that
      another factor, such as parathyroid hormone, is a predominant downregulator of
      VDR.

PMID- 1376961
TI  - Agents that inhibit histamine release: a review.

PMID- 1376962
TI  - [The evaluation of the effects of bunazosin hydrochloride in the treatment of
      prostatic hyperplasia].
AB  - Thirty-five patients with prostatic hyperplasia were entered into a randomized
      controlled study using bunazosin hydrochloride(alpha 1-adrenergic blocker).
      Eighteen patients were allocated to be treated with an initial dose of 1.5 mg/day
      (group 1) and 17 patients received an initial dose of 3.0 mg/day (group 2).
      Subjective symptoms and parameters of urodynamic studies were evaluated after 4
      weeks and 12 weeks. There were 5 withdrawals or exclusions within 4 weeks and 6
      within 12 weeks. Therefore, 15 patients in group 1 and 15 patients in group 2
      were eligible for evaluation at 4 weeks, 12 patients in group 1 and 11 patients
      in group 2 were eligible for evaluation at 12 weeks. The rates of the improvement
      in subjective symptoms such as retarded urination, protracted urination, weakened
      urinary stream, abdominal straining on voiding, and sense of residual urine were
      40%, 25% in group 1 and 46.7%, 36.4% in group 2, at 4 weeks and at 12 weeks,
      respectively. The rate of improvement in objective parameters of the urodynamic
      study such as voiding volume, residual volume, maximum flow rate and average flow
      rate were 26.7%, 16.7% in group 1 and 26.7%, 20.0% in group 2, at 4 weeks and at
      12 weeks, respectively. Thus, these improvements were not correlated with the
      dosage of drug. Adverse effects such as diarrhea, mild headache, palpitation and
      gastric disturbance were observed in 2 patients in group 1, and 3 patients in
      group 2. In the 24 patients treated with the drug over 12 weeks, there were no
      specific adverse effects due to prolonged administration. These findings showed
      that bunazosin hydrochloride is beneficial for the treatment of prostatic
      hyperplasia, and could be safety administered for a prolonged period of time up
      to 12 weeks.

PMID- 1376963
TI  - Genetic epidemiology of beta-thalassemia in Sicily: do sequences 5' to the G
      gamma gene and 5' to the beta gene interact to enhance HbF expression in beta
      thalassemia?
AB  - The present epidemiological study of the molecular characteristics of beta
      thalassemia in Sicily was prompted by the disparate phenotypic expression (in
      clinical status and absolute HbF level) observed in two beta-thalassemic
      homozygotes who were also homozygous for the beta-like globin gene cluster
      haplotype III. We suspected that polymorphisms within haplotype III could be the
      cause for the discrepancy. Based on the association of particular conformations
      of the (AT)xT(y) motif (-540 5' to the beta gene) with milder forms of
      thalassemia and sickle cell anemia, 38 homozygous beta-thalassemia patients were
      studied to define their haplotypes, the -158 site 5' to the G gamma gene (linked
      to haplotype III) and the structure of the (AT)xT(y) motif. We found that the
      patient who was phenotypically mild and homozygous for beta-thalassemia,
      haplotype III, and the -158 C----T mutation was homozygous for the rare (AT)9T5
      motif. In contrast, the patient homozygous for beta-thalassemia, haplotype III,
      and the -158 mutation, but exhibiting a severe clinical course, was homozygous
      for the (AT)7T7 configuration. Others have suggested that (AT)9T5 is a negative
      regulatory protein binding sequence, and it is a silent carrier state for beta
      thalassemia. The usual configuration (AT)7T7, has considerably less affinity for
      regulatory protein binding, and it is the most common configuration in Sicilian
      beta-thalassemics (67 of the 78 chromosomes studied). Within the 38 patients
      studied, seven were informative because they had various combinations of the
      (AT)9T5 and (AT)7T7 motif, and the -158 C----T mutation. The results in these
      patients suggest that only the co-presence of the (AT)9T5 configuration and a C--
      -T change at -158 5' to the G gamma gene is associated with high HbF expression
      and a mild clinical phenotype. We postulate that these two regions of the beta
      like globin gene cluster interact, when endowed with the proper sequences, to
      enhance the expression of HbF secondary to anemia.

PMID- 1376964
TI  - Acute undifferentiated leukemia (AUL): a case report and a proposed system of
      classification.
AB  - This report describes a case of HLADR+, CD34- acute undifferentiated leukemia
      (AUL) diagnosed in an 18-year-old male. A definition of AUL and a system for its
      classification are proposed on the basis of the current state of knowledge about
      phenotypic features of AUL cells and their clonal counterparts that exist during
      early stages of normal hematopoiesis.

PMID- 1376966
TI  - Molecular diagnostics for myelin proteolipid protein gene mutations in Pelizaeus
      Merzbacher disease.
AB  - Pelizaeus-Merzbacher disease (PMD) is a clinically heterogeneous, slowly
      progressive leukodystrophy. The recent detection of mutations in the myelin
      proteolipid protein (PLP) gene in several PMD patients offers the opportunity
      both to design DNA-based tests that would be useful in diagnosing a proportion of
      PMD cases and, in particular, to evaluate the diagnostic utility of single-strand
      conformation polymorphism (SSCP) analysis for this disease. A combination of SSCP
      analysis and direct sequencing of PCR-amplified DNA was used to screen for PLP
      mutations in 24 patients affected with leukodystrophies of unknown etiology. Two
      heretofore undescribed mutations in the PLP gene were identified, Asp202His in
      exon 4 and Gly73Arg in exon 3. The ease and efficiency of SSCP analysis in
      detecting new mutations support the utilization of this technique in screening
      for PLP mutations in patients with unexplained leukodystrophies.

PMID- 1376965
TI  - Substitution of arginine for glycine 325 in the collagen alpha 5 (IV) chain
      associated with X-linked Alport syndrome: characterization of the mutation by
      direct sequencing of PCR-amplified lymphoblast cDNA fragments.
AB  - A large kindred with adult-type X-linked Alport syndrome was studied with regard
      to a defect in the recently described COL4A5 collagen gene. Southern blot
      analysis with COL4A5 cDNA probes showed loss of a MspI restriction site. Direct
      sequencing of cDNA amplified from lymphoblast mRNA demonstrated a single-base
      substitution converting a glycine codon to arginine at position 325 in the alpha
      5 chain of type IV collagen. The triple-helical collagenous domain of alpha
      5(IV), characterized by a Gly-X-Y repeat sequence, is interrupted 22 times by
      noncollagenous sequences. The mutation creates an additional interruption in the
      Gly-X-Y repeat motif, between interruptions 4 and 5. It is interesting that such
      glycine substitutions inside the COL1A1 or COL1A2 genes have been associated with
      many cases of osteogenesis imperfecta. This gly325-to-arg substitution presumably
      alters the triple-helix formation, and, in turn, modifies the ultrastructural and
      functional characteristics of the type IV collagen network inside the glomerular
      basement membrane.

PMID- 1376967
TI  - Ventricular extrasystoles with syncopal episodes, perodactyly, and Robin in
      sequence in three generations: a new inherited MCA syndrome?
AB  - We observed the combination of the Robin sequence with perodactyly (hypoplasia
      and/or agenesis of the distal phalanx of the toes) and cardiac arrhythmia
      (ventricular extrasystoles occurring as bigemini or multifocal tachycardia with
      syncopal episodes) in 6 relatives in 3 generations. This familial association has
      not been reported before and probably represents a previously unrecognized
      heritable malformation syndrome.

PMID- 1376968
TI  - Protease inhibitors as a model for NCL disease, with special emphasis on the
      infantile and adult forms.
AB  - An animal model of NCL disease has been developed with the use of protease
      inhibitors. Young rats received a continuous infusion of various specific
      protease inhibitors or of physiological saline into the lateral ventricle of the
      brain using osmotic mini-pumps. Treatment lasted for 2 weeks, at which time
      animals were sacrificed and the brains were removed and processed for light or
      electron microscopic analysis. The thiol protease inhibitors leupeptin and E64C,
      but not saline or the serine protease inhibitor aprotinin, caused a massive
      accumulation of ceroid-lipofuscin (CL) in brain cells that bore a strong
      morphological resemblance to the CL in the infantile and adult forms of NCL
      disease, and bore similarity to the CL of the late infantile and juvenile forms.
      Leupeptin also caused the death of cerebellar Purkinje cells, as is seen in the
      infantile and adult forms of NCL. Further evidence is presented in support of the
      hypothesis (Ivy et al.: Science 226:985-987, 1984) that decreased or defective
      lysosomal thiol proteases or their substrates may underly the pathogenesis of at
      least the infantile and adult forms of NCL disease. Administration of protease
      inhibitors to the brains of young rats provides an important model for studying
      the cellular mechanisms of ceroid-lipofuscino-genesis.

PMID- 1376969
TI  - Altered protein patterns in brains of children with neuronal ceroid
      lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses (NCL) are a group of inherited
      neurodegenerative diseases characterized by massive intralysosomal accumulation
      of storage materials. We have studied the protein patterns in 5 NCL, 5 control,
      and one Alzheimer disease brains. When protein patterns in NCL and control brain
      gray matter homogenates were examined by SDS-PAGE, NCL brains showed an absence
      or greatly reduced amounts of the Mr 160-180 kDa component and reduced amounts of
      the Mr 29-36 kDa component. Concomitantly, an increase in several components with
      Mrs of 45-50 kDa was noted. The 180 kDa polypeptide appears to be a glycoprotein
      because it was bound to the lectins concanavalin A and Ulex europaeus. Recently,
      the abnormal processing of amyloid protein precursor (APP) and its potential role
      in NCL have been suggested. Possible defects in tissue proteases and protease
      inhibitors may be considered responsible for the presence of these amyloid beta
      protein precursor fragments. To examine this possibility we are using polyclonal
      antibodies to the C terminal 672-695 (APP) and monoclonal antibodies to inter
      alpha-trypsin inhibitor. Polypeptides with molecular weights of approximately 35
      38 kDa were detected in the NCL brain, but not in controls in both cases. These
      findings suggest abnormal protein processing in NCL brain tissue, disturbances in
      protein and glycoconjugate metabolism, impaired lysosomal function (i.e.,
      metabolic enzyme and/or proteases/proteinase inhibitor abnormalities), and the
      involvement of improperly processed APP.

PMID- 1376970
TI  - Regional variability of colonocyte growth and differentiation in the rat.
AB  - The location of stem cells and the direction of colonocyte migration in the
      normal rat colonic crypt were investigated using a serial bromodeoxyuridine
      (BrdU) and [3H]thymidine labeling protocol. The results demonstrate that in the
      distal colon the stem cells are located in the crypt base and that cells migrate
      up toward the luminal surface. In the proximal colon, however, the stem cells are
      located in the midcrypt, and the colonocytes migrate in two directions, up toward
      the luminal surface and down toward the crypt base.

PMID- 1376971
TI  - Temporary cerebral ischemia. Effects of pentastarch or albumin on reperfusion
      injury.
AB  - Recent investigations have proposed that, after temporary ischemia, pentastarch
      may reduce microvascular permeability and reperfusion injury. However, this
      hypothesis has not been tested in the brain. Accordingly, after 180 min of
      temporary middle cerebral artery occlusion, the effect of pentastarch or albumin
      on blood-brain barrier permeability and cerebral injury was investigated in
      isoflurane-anesthetized rats. One of the following was maintained for the final
      60 min of occlusion and throughout reperfusion: control-hematocrit was not
      manipulated; pentastarch-hematocrit was decreased to approximately 30% with
      pentastarch; or albumin-hematocrit was decreased (approximately 30%) with
      albumin. Part A (n = 21): 30 min of reperfusion was allowed, and blood-brain
      barrier permeability was determined with the indicator dye Evans Blue. Part B (n
      = 14): in different animals, 120 min of reperfusion was allowed, and cerebral
      injury (2,3,5-triphenyltetrazolium chloride stain) and edema (specific gravity)
      were assessed. Part C (n = 4): in different animals, the blood-brain barrier was
      evaluated by electron microscopy. Evans Blue (micrograms per gram brain tissue,
      mean +/- SD) was greater in the control (20.8 +/- 9.0) and albumin (15.5 +/- 7.3)
      groups versus the pentastarch (4.7 +/- 2.7) group (P less than 0.05). Brain
      injury (percent of hemisphere ipsilateral to occlusion) was less and specific
      gravity greater in the pentastarch (33 +/- 8 and 1.040 +/- 0.003 respectively)
      versus the albumin group (45 +/- 6 and 1.035 +/- 0.003). This study supports the
      hypothesis that during temporary cerebral ischemia, pentastarch decreases brain
      injury and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1376972
TI  - Allergy to cefazolin: study of in vivo cross reactivity with other betalactams.
AB  - We present two cases of hypersensitivity to cefazolin (one anaphylaxis). The skin
      prick tests with cefazolin at therapeutic concentration were positive. For the in
      vitro study we used conjugates of cefazolin with human serum albumin, obtaining a
      positive result in the histamine release test in both patients. In one case, we
      demonstrated anticefazolin-specific IgE antibodies by RAST. The controls did not
      react to any of these tests. Finally, we carried out skin tests and challenge
      tests with other betalactam antibiotics, including benzylpenicillin, amoxicillin,
      aztreonam, cefuroxime and cefotaxime, showing in both patients good tolerance to
      all these drugs.

PMID- 1376973
TI  - Wilderness injuries and illnesses.
AB  - STUDY OBJECTIVE: To determine injury and illness patterns and occurrence rates
      during wilderness recreation. DESIGN: Prospective injury and illness surveillance
      study. SETTING: Wilderness areas throughout the Western hemisphere. TYPE OF
      PARTICIPANTS: All students and instructors on National Outdoor Leadership School
      courses over a five-year period. MAIN RESULTS: A single fatality occurred,
      resulting in a death rate of 0.28 per 100,000 person-days of exposure. Injuries
      occurred at a rate of 2.3 per 1,000 person-days of exposure. Sprains and strains
      and soft tissue injuries accounted for 80% of the injuries. The illness rate was
      1.5 per 1,000 person-days of exposure. Sixty percent of illnesses were due to
      nonspecific viral illnesses or diarrhea; hygiene appeared to have a significant
      impact on the incidence of these illnesses. Thirty-nine percent of the injuries
      and illnesses required evacuation (1.5 per 1,000 person-days of exposure).
      CONCLUSION: The injury and illness patterns indicate that wilderness medical
      efforts should concentrate on wilderness hygiene and management of
      musculoskeletal injuries and soft tissue wounds. The data also indicate that
      wilderness activities can be conducted relatively safely, but the decision to
      participate should be individualized, with an understanding of risks versus
      benefits.

PMID- 1376974
TI  - Palliative care protocol.

PMID- 1376975
TI  - Expression of intermediate filament proteins in the adult human vestibular
      labyrinth.
AB  - The immunohistochemical detection of intermediate filament proteins, cytoskeletal
      constituents that allow the characterization of tissues, was investigated in
      frozen sections of the chemically fixed, nondecalcified, adult human vestibular
      labyrinth. Cytokeratins (CKs) were detected in all epithelia (including the
      sensory epithelia), although substantial differences in the degree of staining
      between individual cells occurred. The expression of CKs 7, 8, 18, and 19 as
      detected with our subunit-specific monoclonal antibodies in the vestibular
      epithelia is typical of "simple" epithelia and is identical to the CK subtypes
      found in the human cochlea. Although immunostaining for CK 7 was very weak and
      was limited to certain vestibular wall cells, the other CKs demonstrated a
      pronounced and rather uniform distribution throughout the different epithelia.
      All epithelia (including the sensory epithelia) displayed expression of vimentin,
      thus demonstrating co-expression with CKs. Vimentin was also present in the
      subepithelial connective tissue fibroblasts and mesothelial lining of the
      vestibular labyrinth. Neurofilament proteins were detected in all neuronal
      structures. The intense staining for CKs in the maculae and cristae implies that
      these sensory organs are rigid structures, a finding that may possibly be of
      importance in the mechanoelectrical transduction process for the sense of
      equilibrium.

PMID- 1376976
TI  - Primary salivary gland amyloidosis causing sicca syndrome.
AB  - Sicca syndrome (SS), consisting of xerostomia and xerophthalmia, may be caused by
      various disease processes. We present a unique case of SS secondary to primary
      amyloidosis. Amyloidosis is a rare but definite cause of SS and should be
      included in the differential diagnosis of any patient who presents with sicca
      symptoms. A literature review comparing amyloidotic patients with SS and patients
      with amyloidosis only demonstrates that both of these groups of patients present
      similarly with regard to symptoms. However, the majority of patients with SS
      present with sicca symptoms initially in addition to symptoms of amyloidosis.
      These SS patients also present with proteinuria and negative serology test
      results. Therefore, patients presenting with sicca symptoms, proteinuria, and
      negative serologic findings should be suspect for amyloidosis. The importance of
      distinguishing the diagnosis of Sjogren's syndrome from SS in these patients
      cannot be overemphasized. There is a significantly higher incidence of developing
      a lymphoma in Sjogren's syndrome patients. This has important implications for
      the head and neck surgeon treating these patients.

PMID- 1376977
TI  - Epithelial-myoepithelial carcinoma of salivary glands.
AB  - Epithelial-myoepithelial carcinomas comprise approximately 1% of all salivary
      gland neoplasms. They are preponderantly tumors of the parotid glands with a
      relatively low mortality but a decided locoregional aggressiveness.
      Histopathologically, the carcinomas are characterized by a dual cell population
      of epithelial (ductal) cells and myoepithelial cells. These cells vary in their
      dominance and phenotypic expression.

PMID- 1376978
TI  - [Prevention of deep venous thrombosis and postoperative pulmonary embolisms
      (general, gynecological and orthopedic surgery)].

PMID- 1376979
TI  - Glomerular and tubular proteinuria in type 1 (insulin-dependent) diabetic
      patients with and without retinopathy.
AB  - We compared the urinary excretion of albumin, transferrin, N-acetyl-beta-D
      glucosaminidase and alpha-1-microglobulin in 78 Type 1 (insulin-dependent)
      diabetic patients: 39 with retinopathy and 39 without. The two groups were
      matched for age, sex and duration of diabetes. The patients with retinopathy had
      increased excretion (median and range) of albumin [1.7(0.3-399.1) versus 1.0(0.3
      116.6) mg/mmol creatinine, P less than 0.05], transferrin [114.2 (4.1-37126.2)
      versus 33.4 (1.0-4176.7) micrograms/mmol creatinine, P less than 0.01] and N
      acetyl-beta-D-glucosaminidase [23.8 (1.1-119.1) versus 15.0 (0.1-65.1)
      mumol/h/mmol creatinine, P less than 0.05] but not alpha-1-microglobulin.
      Transferrin excretion correlated with albumin excretion. The prevalence of
      increased transferrin excretion (transferrinuria) was greater than that of
      microalbuminuria in patients both with and without retinopathy (P less than 0.01
      in both cases). Urinary transferrin seems likely to be predominantly of
      glomerular origin and merits prospective longitudinal evaluation as a potential
      index of the microangiopathic process.

PMID- 1376980
TI  - Alleviation of non-islet cell tumour hypoglycaemia by growth hormone therapy is
      associated with changes in IGF binding protein-3.
AB  - The hypoglycaemia caused by non-islet cell tumours is often associated with an
      increase in plasma insulin-like activity. In many cases there is a relative if
      not always absolute increase in plasma insulin-like growth factor II (IGF-II).
      Growth hormone (GH) secretion is almost invariably depressed as is the plasma
      insulin response to oral glucose. Despite the high concentration of IGFs (i.e.
      IGF-I and IGF-II) normally found in the plasma of healthy people their potential
      hypoglycaemic effect is not manifest due to the tightness with which they are
      bound to specific binding proteins (IGFBPs). Plasma levels of the major binding
      protein (IGFBP-3), which is GH-dependent, were depressed in three patients with
      tumour induced hypoglycaemia. Treatment with biosynthetic GH restored IGFBP-3 to
      levels which were approximately equimolar to total plasma IGF concentrations,
      alleviated the hypoglycaemia and restored the plasma insulin responses to oral
      glucose. We suggest that after GH treatment IGF-II is sequestered by stimulated
      IGFBP-3 in association with a pre-existing acid-labile subunit to form high
      molecular weight complexes which prevent IGF-II gaining access to tissues
      receptors through which it exerts its hypoglycaemic effects.

PMID- 1376981
TI  - Early detection of Down's syndrome using free beta human choriogonadotropin.

PMID- 1376983
TI  - [Turner's syndrome is not what it was in the past].

PMID- 1376982
TI  - Molecular and microscopic identification of sulfate-reducing bacteria in
      multispecies biofilms.
AB  - The population architecture of sulfidogenic biofilms established in anaerobic
      fixed-bed bioreactors was characterized by selective polymerase chain reaction
      amplification and fluorescence microscopy. A region of the 16S rRNA common to
      resident sulfate-reducing bacteria was selectively amplified by the polymerase
      chain reaction. Sequences of amplification products, with reference to a
      collection of 16S rRNA sequences representing most characterized sulfate-reducing
      bacteria, were used to design both general and specific hybridization probes.
      Fluorescent versions of these probes were used in combination with fluorescence
      microscopy to visualize specific sulfate-reducing bacterial populations within
      developing and established biofilms.

PMID- 1376984
TI  - Cytotoxic effects of hexavalent chromium in cultured murine macrophages.
AB  - The in vitro effect of hexavalent chromium (CrVI) on mouse peritoneal macrophages
      was investigated. Our results demonstrate the existence of a threshold
      concentration of 2.5 microM of CrVI above which chromium affects the viability of
      macrophages in a concentration dependent manner. Morphological changes were seen
      with increasing concentrations of chromium. Evidence is presented that protein
      production (virus-induced interferon) in murine peritoneal macrophages was
      impaired by hexavalent chromium at low concentrations, while random migration and
      phagocytic activity were only affected at high concentrations of CrVI.

PMID- 1376985
TI  - Effects of streptozotocin diabetes on amylase release and cAMP accumulation in
      rat parotid acinar cells.
AB  - Rat parotid responses to sympathetic nerve stimulation in vivo are impaired 2-4
      weeks after the induction of streptozotocin diabetes. In this study, the effects
      of experimental diabetes of similar duration and severity on noradrenaline
      stimulated amylase release and cAMP accumulation were examined in vitro. Amylase
      levels were significantly lower in acinar cells isolated from diabetic animals
      than in controls, and cellular amylase increased after treatment of the diabetic
      animals with either thyroxine (T4) or insulin. Diabetes and T4 had no apparent
      affect on amylase release measured as a percentage of the total. In contrast,
      giving insulin resulted in a significant reduction in maximal secretion (20.4 +/-
      2.4% compared with 43.6 +/- 7.6%). Similar results were observed when amylase
      release was stimulated with forskolin. Basal cAMP levels were unaffected by
      diabetes or T4 (7.8 +/- 2.3 pmol/mg protein), but stimulated cAMP levels were
      significantly greater in diabetic acinar cells than in controls. Insulin reversed
      the effects of diabetes on cAMP accumulation, whereas T4 had no effect. Thus,
      diabetes (2-4 weeks) and insulin in vivo appear to have paradoxical effects on
      parotid amylase release and cAMP accumulation in vitro. Further, the effects of
      diabetes appear to be unrelated to thyroid status.

PMID- 1376987
TI  - Histological evaluation of the effect of transseptal fibre resection on the rate
      of physiological migration of rat molar teeth.
AB  - Twenty-seven female Sprague-Dawley rats were given lead acetate as a vital stain,
      and rates of alveolar bone formation, representative of drift, were measured
      histologically. Teeth around which the transseptal fibre system had been
      destroyed drifted less quickly on both functioning (p less than 0.01) and non
      functioning (p less than 0.001) sides than those with intact transseptal fibres.
      Both horizontal and vertical components of physiological drift were equally
      affected by destruction of the transseptal fibre system. It was felt that the
      transseptal fibres probably exerted their primary effect on the tooth, with bone
      remodelling around the drifting tooth being affected secondarily.

PMID- 1376986
TI  - Amylase mRNA synthesis and ageing in rat parotid glands following isoproterenol
      stimulated secretion.
AB  - In the parotid, as well as in other exocrine glands, secretory protein synthesis
      declines with age. However, whether this decline in the steady-state rate of
      protein synthesis reflects the reduced digestive activity of the animal or actual
      cellular alterations that affect synthesis is unknown. Here the ability to
      synthesize amylase and its mRNA during the period of enhanced protein synthesis
      following secretion induced by isoproterenol was compared in acinar cells of 2
      and 24-month-old rats. In unstimulated glands, rates of synthesis of total
      protein and amylase, as well as amounts of amylase mRNA, were significantly less
      in the older rats than in their younger counterparts. After stimulation with
      isoproterenol, which induced the secretion of about 50% of stored proteins, rates
      of synthesis of total protein, as well as amylase, were increased by about 2.5 x
      the unstimulated rates in both age groups. However, the amount of amylase mRNA
      did not increase in parallel with the increase in the rate of amylase protein
      synthesis in both young and old rats. The molecular size of the mRNA was the same
      in stimulated and unstimulated glands of both age groups. Thus, it appears that
      parotid acinar cells from old rats can be stimulated to synthesize secretory
      proteins at an increased rate. It remains to be determined what causes the
      reduced rate of protein synthesis in unstimulated glands in old rats.

PMID- 1376988
TI  - bFGF enhances the development of the collateral circulation after acute arterial
      occlusion.
AB  - An adequate collateral circulation is crucial to tissue survival subsequent to
      proximal major arterial occlusion. The precise mechanism of collateral blood
      vessel development and the biochemical mediators involved in this process are
      unknown. To evaluate the influence of a number of agents on the development of
      the collateral circulation, we developed a rat model of severe hind limb
      ischaemia. The recovery of blood flow after acute arterial occlusion was
      increased by exogenous basic fibroblast growth factor and heparin, and decreased
      by protamine. Erucamide (cis-13-docosenamide), an angiogenic lipid, had no effect
      on collateral blood flow. These results indicate that basic fibroblast growth
      factor and heparin are potential therapeutic agents in the treatment of
      peripheral vascular disease.

PMID- 1376990
TI  - Characterization of a rat variant alpha-fetoprotein.
AB  - The rat adult liver and hepatocyte lines express an 1.7-kb variant alpha
      fetoprotein (AFP) mRNA which differs from the 2.2-kb fetal AFP transcript in
      sequence in the 5' region. Here we report the characterization of a variant AFP
      cDNA, ARFP9, which is 1349 bp in length and encodes a 325 amino acid polypeptide.
      Nucleotides 225 to the 3' end (1125 bp) in ARFP9 corresponds exactly to
      nucleotide 873 to the 3' end of the fetal AFP mRNA. However, the first 224-bp of
      ARFP9, which is located in the 7th intron (designated the V exon) of the rat AFP
      gene, is not present in the 2.2-kb fetal AFP transcript. The size of the V exon
      is about 266-bp. In vitro expression experiments showed that the variant AFP is
      an unglycosylated intracellular protein of 37 kDa. Methyl-isobutyl-xanthine (MIX)
      stimulated expression of the fetal AFP mRNA but inhibited expression of the
      variant AFP mRNA, suggesting that in the rat, the two AFP transcripts are
      developmentally and differentially regulated.

PMID- 1376989
TI  - Ca(2+)-dependent and Ca(2+)-independent mechanisms modulate whole-cell cationic
      currents in human neutrophils.
AB  - We used whole-cell, voltage-clamp methodology to study the activation and
      inhibition of cationic currents in neutrophil. Cationic channels involved were
      impermeable to N-methyl-D-glucamine and to choline, but permeable to Na+, K+,
      Cs+, tris(hydroxymethyl)amino-ethane, and tetraethylammonium. N-formyl-L
      methionyl-L-leucyl-L-phenylalanine, the Ca(2+)-ionophore A23187, and phorbol
      myristate acetate activated the cationic current. Activated currents showed
      voltage dependence and outward rectification. The Ca(2+)-chelator 1,2 bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetate markedly inhibited A23187-induced
      currents, but only partially decreased phorbol ester- or chemoattractant-induced
      currents. Dibutyryl cAMP diminished only the chemoattractant-induced currents.
      The adenosine analogs 5'N-ethylcarboxamidoadenosine and N6-cyclohexyladenosine
      blocked the currents induced by all agents. Thus, we conclude that activation and
      inhibition of cationic channels in human neutrophils involve both Ca(2+)
      dependent and Ca(2+)-independent mechanisms.

PMID- 1376991
TI  - Kinins mediate kallikrein-induced endothelium-dependent relaxations in isolated
      canine coronary arteries.
AB  - ACE inhibitors elicit the release of endothelium-derived relaxing factors in
      perfused isolated canine arteries (Mombouli and Vanhoutte, J. Cardiovasc.
      Pharmacol. 1991, 18: 926-927); this action is antagonized by bradykinin-receptor
      antagonists suggesting that it is mediated by local kinin generation. The effects
      of exogenous tissular kallikrein (porcine) were examined in vitro in the isolated
      canine coronary artery. Isometric tension was measured in blood vessel rings
      (with and without endothelium) contracted with prostaglandin F2 alpha. The
      kallikrein elicited relaxations in rings with, but not in those without,
      endothelium. This response was augmented by the angiotensin converting enzyme
      inhibitor perindoprilat, and it was antagonized by the selective B2-kinin
      receptor antagonist HOE 140 and aprotinin, an inhibitor of tissular kallikrein.
      These data suggest that in the canine coronary artery, kallikrein causes
      relaxations that may be mediated by kinins generated from endogenous kininogens
      present in the vascular wall.

PMID- 1376992
TI  - Alternative splicing products of the tenascin gene distinguish rat liver fat
      storing cells from arterial smooth muscle cells and skin fibroblasts.
AB  - Fat storing-(Ito-)cells (FSC) transform into a myofibroblast-like cell type
      during liver fibrogenesis. A similar development can be observed in cell culture.
      At the moment, a definite marker to differentiate transformed FSC from smooth
      muscle cells (SMC) is not available. We recently found that FSC, SMC and skin
      fibroblasts (SF) synthesize tenascin, a novel matrix protein. As it is reported
      that various tissues express different tenascin forms by the mechanism of
      alternative pre-mRNA splicing, we analyzed the tenascin transcripts in these cell
      types. Total RNA extracted from cultured FSC, SMC and SF, analyzed by Northern
      blot hybridization, showed a 7.2 kb transcript in FSC, a 8.7 kb mRNA in SMC,
      whereas SF produced both messages. As the splicing pattern of FSC in primary
      culture did not change after passaging, this differential expression of tenascin
      mRNA might provide a tool to identify myofibroblast-like cells derived from FSC.
      The important fibrogenic mediator transforming growth factor-beta (TGF-beta)
      increased tenascin gene expression in each cell type. In SMC, TGF-beta
      additionally induced the production of the 7.2 kb transcript. Determination of
      tenascin transcripts will allow to examine the purity of FSC cultures and
      facilitate a better identification of the cells involved in liver fibrosis.

PMID- 1376993
TI  - A calcium-dependent cation channel in mast cell granule membranes reconstituted
      into a lipid bilayer.
AB  - Secretory granules isolated from rat peritoneal mast cells were reconstituted
      into a lipid planar bilayer and membrane current was measured. A novel calcium-
      and voltage-dependent cation channel with single-channel conductances of 80 pS
      for fully open and 60 pS for sub-conducting states was detected. This channel
      opened only when potential of the cis compartment, which corresponds to the
      cytoplasmic side in the cell, was positive with respect to the trans compartment
      and only when Ca concentration of the cis compartment was higher than 10(-7) M.
      The open channel probability further increased, depending on the concentration of
      Ca. The physiological role of this channel remains to be determined.

PMID- 1376994
TI  - Human autoantibody binding to multiple conformations of DNA.
AB  - Systemic lupus erythematosus and rheumatoid arthritis in humans are characterized
      by circulating and tissue fixed autoantibodies reactive with self antigens
      including nucleic acids and other nuclear components. Native calf thymus DNA (B
      form), DNA.RNA hybrid (A-form), and left handed DNA (Z-form) were reactive with
      autoantibodies derived from SLE sera. Inhibition studies suggest that antibodies
      are recognizing multiple conformations presented by altogether different polymers
      and A- or Z-DNA might be the immunogenic stimulus for the production of
      antibodies cross reactive with native DNA.

PMID- 1376995
TI  - Induction of propranolol metabolism by the azo dye sudan III in rats.
AB  - Effects of the azo dye sudan III, an inducer of cytochrome P450 isozymes
      belonging to the CYP1A subfamily, on propranolol (PL) in vitro and in vivo
      metabolism were investigated in rats. The kinetic parameters of the activity for
      each metabolic pathway were determined in liver microsomes from control and sudan
      III-treated rats. Sudan III pretreatment increased extensively PL 4-hydroxylase,
      5-hydroxylase and N-desisopropylase activities at high but not at low PL
      concentrations. On the other hand, kinetic parameters of 7-hydroxylase activity
      were not affected by sudan III pretreatment. Sudan III pretreatment decreased
      blood concentrations of PL after intraportal infusion of PL at high doses (12.5
      and 20 mg/kg), but not at a low dose (5 mg/kg). These observations were
      consistent with data obtained from the in intro studies showing that sudan III
      pretreatment induced low-affinity but not high-affinity cytochrome P450 isozymes
      involved in PL metabolism in rat liver microsomes.

PMID- 1376996
TI  - Differential wound activation of members of the phenylalanine ammonia-lyase and 4
      coumarate:CoA ligase gene families in various organs of parsley plants.
AB  - We analyzed the developmental regulation and the activation by wounding of
      several stress-related genes in various parsley organs. The genes encode
      phenylalanine ammonia-lyase (PAL) and 4-coumarate:CoA ligase (4CL), two enzymes
      of general phenylpropanoid metabolism; a flavonoid specific enzyme, chalcone
      synthase (CHS); a furanocoumarin specific enzyme, bergaptol O-methyltransferase
      (BMT); and a pathogenesis-related protein (PR 1). All genes or gene families
      exhibited high levels of expression in roots and during certain stages of leaf
      development. PAL, 4CL and CHS were preferentially expressed in young leaves, BMT
      and PR 1 in old leaves. An appreciable increase in CHS mRNA levels was observed
      in wounded leaves. By contrast, root wounding led to a decrease in the existing
      CHS mRNA levels. A biphasic response (a decrease followed by an increase) to
      wounding was seen for BMT and PR 1 mRNAs in roots and for BMT mRNA in attached
      leaves. Using gene-specific oligonucleotide probes to measure the expression
      rates of three of the four PAL genes and of the two 4CL genes separately we
      observed a differential behavior of the individual family members under many of
      the conditions tested. While PAL-3 was preferentially activated in wounded leaves
      and 4CL-1 in wounded roots, PAL-2 and 4CL-2 were primarily responsible for the
      high constitutive expression levels in roots and flowering stems respectively.
      Despite the differential expression of their individual members, the PAL and 4CL
      gene families displayed very similar changes in the overall patterns of
      expression, reflecting their closely related functions in phenylpropanoid
      metabolism.

PMID- 1376997
TI  - Clinical value of the assessment of gynaecological tumour angiogenesis by
      transvaginal colour Doppler.
AB  - Angiogenesis occurs in the body in only a few physiological conditions, but it
      regularly precedes carcinogenesis. Neovascularisation is a term well known to the
      pathologist, but with the advent of colour Doppler it is now of interest to those
      using ultrasonography. Since morphological criteria alone are insufficient to
      characterise space occupying lesions, visualisation of newly formed vessels and
      consequently, their blood flow characteristics, seems to provide a clearer
      distinction in vivo between benign and malignant gynaecological tumours. Very low
      resistance indices in newly formed vessels, as a predictor of malignancy, have
      already been established. The most recent area of investigation covering the
      differences between centrally and peripherally placed vessels offers additional
      criteria for diagnosing gynecological malignancy.

PMID- 1376998
TI  - Northern and Southern blot analysis of human RNA and DNA in autopsy material.
AB  - Fresh biopsy material for molecular biological investigations is not obtainable
      from all relevant normal human tissues. We studied the feasibility of using RNA
      and DNA from autopsies for Northern and Southern blot analysis. Tissue samples
      from seven organs were obtained from 10 autopsies performed 21-118 h postmortem.
      Extracted RNA and DNA were examined by Northern and Southern blot analysis using
      oligo-labelled human DNA probes recognizing gene transcripts of 2-5 kb. The
      results indicated that, in general, Northern blot analysis was feasible with the
      applied probes when the tissue was obtained less than two days postmortem.
      Histological examination showing slight or no autolysis and the presence of
      ribosomal bands after gel electrophoresis were both indicative parameters of RNA
      preservation. DNA was appropriate for Southern blotting when the tissue was
      obtained less than three to five days postmortem, depending on the organ from
      which the DNA was extracted.

PMID- 1376999
TI  - Effect of nitric oxide production on the redox modulatory site of the NMDA
      receptor-channel complex.
AB  - Nitric oxide (NO) is an important messenger both systemically and in the CNS. In
      digital Ca2+ imaging and patch-clamp experiments, clinically available nitroso
      compounds that generate NO are shown to inhibit responses mediated by the NMDA
      subtype of the glutamate receptor on rat cortical neurons in vitro. A mechanism
      of action for this effect was investigated by using the specific NO-generating
      agent S-nitrosocysteine. We propose that free sulfhydryl groups on the NMDA
      receptor-channel complex react to form one or more S-nitrosothiols in the
      presence of NO. If vicinal thiol groups react in this manner, they can form a
      disulfide bond(s), which is thought to constitute the redox modulatory site of
      the receptor, resulting in a relatively persistent blockade of NMDA responses.
      These reactions with NO can afford protection from NMDA receptor-mediated
      neurotoxicity. Our results demonstrate a new pathway for NO regulation of
      physiological function that is not via cGMP, but instead involves reactions with
      membrane-bound thiol groups on the NMDA receptor-channel complex.

PMID- 1377000
TI  - Signal flow in visual transduction.

PMID- 1377001
TI  - Lymphoblastoid cell adhesion mediated by a dimeric and polymeric endogenous beta
      galactoside-binding lectin (galaptin).
AB  - Glutaraldehyde-polymerized human splenic galaptin, a beta-galactoside-binding
      lectin, was demonstrated to have enhanced hemagglutinating and asialofetuin
      binding activity relative to native dimeric galaptin when these lectins were
      present in solution. The polymerized lectin consisted primarily of 2-, 4- and 12
      membered species after reductive alkylation. Both forms of galaptin bound, at 4
      degrees C, to saturable B lymphoblastoid cell surface receptors. Estimates
      obtained by Scatchard analyses, with the binding data expressed in terms of 14.5
      kDa subunit molarity, were 5 x 10(7) binding sites/cell with affinity constant Ka
      = 2.2 x 10(5) M for dimeric galaptin and 17 x 10(7) binding sites/cell with Ka =
      3.4 x 10(5) M-1 for polymeric galaptin. Both forms of galaptin adsorbed to
      polystyrene with high efficiency; however, only plastic-adsorbed polymeric
      galaptin mediated adhesion of lymphoblastoid cells. Cell adhesion was inhibited
      by lactose. Plastic-adsorbed polymeric galaptin bound asialofetuin more
      efficiently than dimeric galaptin. Asialofetuin binding was inhibited 65% and 30
      50% by lactose for plastic-adsorbed polymeric and dimeric galaptin, respectively.
      Native fetuin bound to the adsorbed dimeric galaptin in a lactose-insensitive
      manner. These data indicate that cell surface receptor-galaptin interaction is
      carbohydrate specific whereas polystyrene-adsorbed galaptin may demonstrate
      protein-protein interactions with soluble ligands.

PMID- 1377002
TI  - TP53 tumor suppressor gene: a model for investigating human mutagenesis.
AB  - More than 350 independent point mutations of the TP53 gene, found in a wide
      variety of human cancers, were compiled and analysed. From this study, we confirm
      the presence of four hot-spot regions which colocalize with some highly conserved
      domains of the protein. We also define a new hot-spot region which is observed
      predominantly in lung tumors. Analysis of the mutational events suggests the
      direct involvement of environmental carcinogens in lung tumors and
      hepatocarcinomas, and spontaneous mutagenesis generating essentially CpG
      transitions in most of the remaining ones. Furthermore, we demonstrate in this
      work that the TP53 gene is an informative model with which to study the molecular
      mechanisms of mutagenesis in the human genome.

PMID- 1377003
TI  - Cytogenetic analysis of renal angiomyolipoma.
AB  - Chromosome analysis of a benign, unilateral, renal angiomyolipoma revealed the
      karyotype 44,XX,-8, -12, -14, -21, +der (8q14q), + der(12)(12pter----12q14
      15::12q24----12q14-15::+ ++21q21----21qter). This indicates that structural
      changes of 12q13-15, which are so frequently observed in the common malignant and
      benign lipogenic tumors, may also occur in the rarer variants of these neoplasms.

PMID- 1377004
TI  - Trisomy 7 in short-term cultures of colorectal adenocarcinomas.

PMID- 1377005
TI  - Cytogenetic analysis of 57 primary prostatic adenocarcinomas.
AB  - Cytogenetic analysis after short-term culture in vitro of primary tumor samples
      was attempted in 82 patients with prostatic cancer. Tumor material was obtained
      by radical prostatectomy or transurethral resection. Successful cytogenetic
      studies were performed on 57 tumors of which five were well, 30 moderately, and
      22 poorly differentiated adenocarcinomas. Only normal karyotypes were found in 24
      tumors. Structural nonclonal aberrations were detected in 18 and clonal
      karyotypic abnormalities in 15 tumors. The most common clonal numerical
      aberration was loss of the Y chromosome; a missing Y was found in six tumors, in
      three of these as the sole anomaly. Clonal structural chromosomal rearrangements,
      usually accompanied by numerical changes, were detected in 12 tumors. The
      rearrangements involved 18 of the 22 autosomes and the X chromosome. Chromosomes
      1, 7, and 10 were most frequently affected. Deletions, duplications, inversions,
      insertions, and balanced as well as unbalanced translocations were represented.
      The breakpoints in chromosome 1 were scattered along both the short and long arms
      with no obvious clustering, whereas those in chromosomes 7 and 10 were clustered
      at bands 7q22 (two deletions and two duplications in four different tumors) and
      10q24 (two translocations, one deletion, and one inversion in four tumors). One
      additional tumor displayed a derivative chromosome 10 with a breakpoint in 10q23,
      and one had monosomy 10. Altogether, these abnormalities resulted in loss of
      10q24----qter in five tumors. Monosomy 8 and rearrangements of the short arm of
      chromosome 8 leading to loss of 8p21----pter were seen in four tumors. Double
      minute chromosomes were found in two tumors.

PMID- 1377006
TI  - Cytogenetic abnormalities in renal oncocytic neoplasms.
AB  - We have performed cytogenetic studies on five renal oncocytic neoplasms (three
      grade 2 tumors and two grade 1 tumors) identified histologically by light
      microscopy. One grade 1 tumor failed to produce mitotic cells. The other four
      tumors exhibited both normal and abnormal cell lines. Numerical abnormalities
      were found in both the single grade 1 and two of the grade 2 tumors whereas
      structural abnormalities were limited to grade 2 tumors. Aneuploidy of chromosome
      12 was observed in both grade 1 and 2 tumors. Grade 2 tumors showed more
      extensive numerical change than the grade 1 tumors. Abnormalities of chromosome 3
      characteristic of renal cell carcinoma were not found in any tumor in this
      series. A combination of C-banding and HaeIII endonuclease banding was used to
      identify an ambiguous marker. In our four cases and in the cases previously
      reported, loss of a sex chromosome, abnormalities of chromosomes 1 and 22, and
      trisomy 12 are findings most often observed in renal oncocytoma.

PMID- 1377008
TI  - Karyotype and T-cell receptor expression in T-lineage acute lymphoblastic
      leukemia.
AB  - The relationship between karyotype and expression of the T-cell receptor (TCR)
      proteins was examined in 19 patients with T-lineage acute lymphoblastic leukemia
      (T-ALL). All patients expressed CD3 molecules in the cytoplasm or on the cell
      membrane. Patients were classified according to TCR expression thus: no TCR
      expression (TCR-), six cases; cytoplasmic expression of TCR beta chain (cTCRB)
      only, six cases; membrane expression of TCR alpha and beta chains (mTCRAB), five
      cases; membrane expression of TCR gamma and delta (mTCRGD), two cases. A
      chromosomally abnormal clone was detected in 15 cases. The most common site of
      chromosomal change was at 14q11 (seven cases), the chromosomal band to which TCRA
      and TCRD have been mapped; as a deletion (two cases); or as a translocation with
      reciprocal breakpoints in bands containing the TCRG (7p15); TCRB (7q35); or
      putative oncogenes HOXII (10q24), RBTN2 (11p13) or MYC (8q24) genes. Breakpoints
      were also seen in 6q (three cases), 9p (two cases), or 11q23 (two cases). The
      following observations were made: All four chromosomally normal cases lacked TCR
      expression (TCR-). Breakpoints at 14q11 were found in one of six TCR- cases, four
      of six cTCRB cases, and two of five mTCRAB cases. Abnormalities of 6q and of 9p
      were seen only in cases with full TCR expression (mTCRAB or mTCRGD).

PMID- 1377007
TI  - A complex genetic rearrangement in a t(10;14)(q24;q11) associated with T-cell
      acute lymphoblastic leukemia.
AB  - The t(10;14)(q24;q11) is observed in the leukemia cells of 5-10% of cases of T
      cell acute lymphoblastic leukemia (T-ALL). Recently, molecular analyses of a
      number of these translocations revealed simple reciprocal translocations between
      the T-cell receptor delta chain gene (TCRD) and a region of 10q24. We have
      characterized, at the molecular level, a t(10;14)(q24;q11) in a patient with T
      ALL. The translocation in this case, in contrast to the previous cases, is part
      of a complex genetic rearrangement. In addition to a reciprocal translocation
      between the D delta 3 gene segment of TCRD and a region of 10q24, a local
      inversion occurred within TCRD, involving the D delta 2 and V delta 2 gene
      segments. As a consequence, the entire joining and constant regions and most of
      the diversity regions of TCRD are located on the derivative 14 chromosome,
      whereas the joining and constant regions of TCRA are positioned on the derivative
      10 chromosome. The chromosome 10 breakpoint in our patient, as in other t(10;14),
      clusters within a 9 kb breakpoint region. The occurrence of seven breakpoints
      within a localized region of chromosome 10 implies the existence of a nearby gene
      whose activation may have conferred a selective advantage on the leukemia cells.
      Moreover, as in the previous cases, the translocation in the present study
      exhibits recombination signal sequences or signal-like sequences adjacent to the
      breakpoint junction. The presence of such motifs suggests the involvement of the
      recombinase enzyme system in the generation of this genetic alteration.

PMID- 1377009
TI  - Karyotype instability and altered differentiation of rat sarcoma cells after
      retroviral infection.
AB  - The karyotypic and phenotypic stability of cultured rat fibrosarcoma cells was
      challenged by infection with Moloney murine sarcoma virus (MoMuSV). After
      transformation, the spindle-like morphology of the parental HH-16 cl.2/1 cells
      had altered to a rounded phenotype, which was maintained in tumors produced by
      inoculating transformed cells into congenic animals. In contrast to the parental
      cells, transformed cells lacked cables of cytokeratins 14-16 and 19 and showed
      reduction of the mesenchymal marker protein vimentin. Additionally, the
      morphologically altered cell clones tf-1 to tf-3 had lost growth arrest in the
      presence of dexamethasone. The DNA of the transformed cells contained between
      four and six randomly integrated proviral copies. Karyotypic alterations were
      manifested by reduction of morphologically intact chromosomes in the MoMuSV
      transformed cells together with increase of structural aberrations. Three
      additional markers were identified in the virus-transformed cell clones.
      Karyotypic instability induced by MoMuSV infection appeared closely related to
      reduction of the cellular differentiation status, although only cells of clone tf
      1 had increased metastatic potential.

PMID- 1377010
TI  - Chromosome aberrations in 35 primary ovarian carcinomas.
AB  - Cytogenetic analysis was performed on short-term cultures of primary ovarian
      carcinomas from 62 patients. Cytogenetic analysis was successful in 59 cases.
      Clonal chromosome aberrations were detected in 35 tumors. Only numerical changes
      or a single structural change were found in five carcinomas: trisomy 12 was the
      sole anomaly in two tumors, one tumor had the karyotype 50,XX, + 5, + 7, + 12, +
      14, a fourth tumor had a balanced t(1;5), and the fifth tumor had an unbalanced
      t(8;15). The fact that four of these five carcinomas were well differentiated
      suggests that simple karyotypic changes are generally characteristic of these
      less aggressive ovarian tumors. The majority of the cytogenetically abnormal
      tumors (n = 30) had complex karyotypes, with both numerical and structural
      aberrations and often hypodiploid or near-triploid stemlines. The numerical
      imbalances (comparison with the nearest euploid number) were mostly losses, in
      order of decreasing frequency -17, -22, -13, -8, -X, and -14. The structural
      aberrations were mostly deletions and unbalanced translocations. Recurrent loss
      of genetic material affected chromosome arms 1p, 3p, 6q, and 11p. The breakpoints
      of the clonal structural abnormalities clustered to several chromosome bands and
      segments: 19p13, 11p13-15, 1q21-23, 1p36, 19q13, 3p12-13, and 6q21-23. The most
      consistent change (16 tumors) was a 19p + marker, and in 12 of the tumors the 19p
      + markers looked alike.

PMID- 1377011
TI  - Specific metaphase and interphase detection of the breakpoint region in 8q24 of
      Burkitt lymphoma cells by triple-color fluorescence in situ hybridization.
AB  - Triple fluorescence in situ hybridization with a plasmid DNA library from sorted
      human chromosomes 8 in combination with bacteriophage clones flanking the
      breakpoint in 8q24 of the Burkitt lymphoma cell line J1 was used for the specific
      delineation of this breakpoint in individual tumor cells. With this approach,
      tumor-specific breakpoints in translocation chromosomes can be detected at all
      stages of the cell cycle with high specificity.

PMID- 1377012
TI  - Clonal aberrations of chromosomes X, Y, 7 and 10 in normal kidney tissue of
      patients with renal cell tumors.
AB  - By means of G-banding techniques, chromosome aberrations were studied in short
      term cultures of normal renal parenchymal cells from 45 patients with renal cell
      carcinoma. Clonal chromosomal aberrations were detected in 29 patients; loss of
      the Y chromosome as well as trisomy X, 5, 7, 9, 10, 12, and 18 was found.
      Chromosomes 7 and 10 were involved preferentially. Results of fluorescence in
      situ hybridization with chromosome 7- and 10-specific DNA probes on non-cultured
      normal kidney cells suggested that the aberrations developed in vivo.

PMID- 1377013
TI  - Trisomy 2 as the sole chromosomal abnormality in a hepatoblastoma.
AB  - Short-term cultures of a fine-needle aspirate from a hepatoblastoma were analyzed
      cytogenetically. Trisomy 2 was found as the sole abnormality, yielding the
      karyotype 47,XY, + 2/46,XY. Because trisomy for all or part of chromosome 2 has
      been described, although together with other aberrations, in seven of the 11
      hepatoblastomas hitherto reported, the finding of + 2 as the only anomaly in the
      present case strongly indicates that additional chromosome 2 material is of
      pathogenetic significance in this tumor type.

PMID- 1377014
TI  - Interstitial loss of the same region of 5q in multiple adenomas and a carcinoma
      derived from an adenomatous polyposis coli (APC) patient.
AB  - Accumulation of genetic alterations in oncogenes and tumor suppressor genes
      causes the transformation of a normal cell into a malignant cell. Recently,
      Fearon and Vogelstein (Cell 61:759-767, 1990) reported on a model for the genetic
      pathway in development of colorectal neoplasia. To investigate genetic
      alterations in colorectal carcinomas, we examined allelic losses on some
      chromosomes in adenomas and carcinomas derived from patients with adenomatous
      polyposis coli (APC). We found evidence for an interstitial deletion of 5q. Loss
      of heterozygosity (LOH) of 5q around the APC locus was observed in both adenoma
      and carcinoma in one case. The fact that the same region of chromosome 5 was lost
      in five adenomas and one carcinoma derived from the same patient suggests that a
      somatic interstitial deletion may be caused not by random mechanisms but by a
      specific mechanism.

PMID- 1377015
TI  - The NM23 gene maps to human chromosome band 17q22 and shows a restriction
      fragment length polymorphism with BglII.
AB  - The NM23-Hl gene is a putative tumor suppressor gene that may be important in the
      metastasic process. Recent genetic and immunological data indicate that the NM23
      Hl gene encodes a protein with nucleoside diphosphate (NDP) kinase activity. The
      mapping of NM23-Hl by panels of rodent-human somatic cell hybrids and in situ
      hybridization showed that the gene is located in human chromosome band 17q22. A
      two-allele polymorphism with BglII was demonstrated.

PMID- 1377016
TI  - Ring chromosomes in a retroperitoneal lipoma of childhood.
AB  - We report here the presence of ring chromosomes in a retroperitoneal lipoma from
      a 12-year-old male. Ring chromosomes are strongly associated with the
      pathological subtype "atypical lipoma" in adults. In contrast, however, the
      tumour described here possesses no atypical features.

PMID- 1377017
TI  - Ph-positive chronic myeloid leukemia with loss of the segment distal to M-bcr.
AB  - We describe a patient with chronic myeloid leukemia (CML) and a 22q- but no 9q+
      chromosome. Southern blot analysis showed a BCR rearrangement. The patient soon
      developed profound and superficial thrombophlebitis in arms and legs and died
      from pulmonary embolisation 15 days after diagnosis. Five CML cases with a
      deletion of 22q but no known translocation of 22q11----qter have been described
      earlier. The present patient is the first such case, however, in whom a BCR
      rearrangement has been demonstrated.

PMID- 1377019
TI  - Chromosome aberrations in an alpha-fetoprotein-producing hepatoblastoma.
AB  - The cytogenetic findings of an alpha-fetoprotein (AFP)-producing hepatoblastoma
      in a 14-month-old girl are reported. Ten of 36 tumor cells were chromosomally
      abnormal, yielding the composite karyotype 47,XX,2q +,
      t(3;5)(p25;q31),dup(4)(q12q26), +20. Three of the chromosomal abnormalities (2q+,
      break at 4q12, +20) have been reported previously and might be of pathogenetic
      significance.

PMID- 1377018
TI  - Localization of the fibroblast growth factor receptor-4 gene to chromosome region
      5q33-qter.
AB  - Our polymerase chain reaction cloning of novel tyrosine kinases expressed in the
      K562 chronic myeloid leukemia cells has revealed a novel fibroblast growth factor
      receptor, FGFR4. We have here mapped the FGFR4 gene by analysis of somatic cell
      hybrids and in situ hybridization to the 5q33-qter chromosomal region. This
      finding is of interest in that the FGFR4 gene is expressed in several leukemia
      cell lines and the 5q33-qter region is involved in nonrandom chromosomal
      translocations in acute myelogenous leukemias and Ki-I lymphomas.

PMID- 1377021
TI  - On the mechanism of a mammalian neuronal type nicotinic acetylcholine receptor
      investigated by a rapid chemical kinetic technique. Detection and
      characterization of a short-lived, previously unobserved, main receptor form in
      PC12 cells.
AB  - The mammalian nicotinic acetylcholine receptor in PC12 cells has many properties
      characteristic of the neuronal receptors involved in key chemical reactions that
      are responsible for signal transmission between cells of the nervous system. This
      report describes initial investigations of the mechanism of this receptor using a
      rapid chemical kinetic technique with a time resolution of 20 ms, which
      represents a 250-fold improvement over the best time resolution (5 s) employed in
      previous studies. Carbamoylcholine, a stable analogue of the neurotransmitter
      acetylcholine, was the activating ligand used, and the concentration of open
      transmembrane receptor-channels in PC12 cells was measured by recording whole
      cell currents at pH 7.4, 21-23 degrees C, and a transmembrane voltage of -60 mV.
      Two receptor forms that account for 80% and 20% of the receptor-controlled
      current were detected; the main receptor form, accounting for 80% of the whole
      cell current, desensitized completely before the first measurements had been made
      in previous studies. Only the main receptor form has been investigated so far
      using the new method. The constants of a mechanism that accounts for the
      concentration of the open transmembrane receptor-channel over a 100-fold range of
      carbamoylcholine concentration were evaluated: the dissociation constant of the
      site controlling channel opening (K1 = 2.0 mM), the channel-opening equilibrium
      constant (phi -1 = 5.0), and the dissociation constant of an inhibitory site to
      which carbamoylcholine binds (KR = 6.5 mM). These evaluated constants allow one
      to calculate Po, the conditional probability that at a given concentration of
      carbamoylcholine the receptor-channel is open. Po was also determined in the
      presence of 2 mM carbamoylcholine by an independent method, the single-channel
      current-recording technique, and the agreement between the Po values obtained in
      two independent ways is within experimental error. This result indicates that the
      time resolution of the chemical kinetic technique employed was sufficient to
      evaluate the constants pertaining to the active state of the receptor, which
      forms a transmembrane channel, before its conversion to desensitized receptor
      forms with different properties. Previous kinetic measurements with a time
      resolution of 5 s showed that many compounds, such as anesthetic-like molecules,
      nerve growth factor, and substance P, modify the function of the neuronal
      receptor in PC12 cells or react specifically with the neuronal but not with the
      muscle receptor, for example, some toxins.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1377020
TI  - Recognition of G-U mismatches by tris(4,7-diphenyl-1,10
      phenanthroline)rhodium(III).
AB  - The coordination complex tris(4,7-diphenyl-1,10-phenanthroline)rhodium(III)
      [Rh(DIP)3(3+)], which promotes RNA cleavage upon photoactivation, has been shown
      to target specifically guanine-uracil (G-U) mismatches in double-helical regions
      of folded RNAs. Photoactivated cleavage by Rh(DIP)3(3+) has been examined on a
      series of RNAs that contain G-U mismatches, yeast tRNA(Phe) and yeast tRNA(Asp),
      as well as on 5S rRNAs from Xenopus oocytes and Escherichia coli. In addition, a
      "microhelix" was synthesized, which consists of seven base pairs of the acceptor
      stem of yeast tRNA(Phe) connected by a six-nucleotide loop and contains a
      mismatch involving residues G4 and U69. A U4.G69 variant of this sequence was
      also constructed, and cleavage by Rh(DIP)3(3+) was examined. In each of these
      cases, specific cleavage is observed at the residue which lies to the 3'-side of
      the wobble-paired U; some cleavage by the rhodium complex is also evident in
      several structured RNA loops. The remarkable site selectivity for G-U mismatches
      within double-helical regions is attributed to shape-selective binding by the
      rhodium complex. This binding furthermore depends upon the orientation of the G-U
      mismatch, which produces different stacking interactions between the G-U base
      pair with the Watson-Crick base pair following it on the 5'-side of U compared to
      the Watson-Crick pair preceding it on the 3'-side of U. Rh(DIP)3(3+) therefore
      serves as a unique probe of G-U mismatches and may be useful both as a model and
      in probing RNA-protein interactions as well as in identifying G-U mismatches
      within double-helical regions of folded RNAs.

PMID- 1377022
TI  - On the mechanism of the gamma-aminobutyric acid receptor in the mammalian (mouse)
      cerebral cortex. Chemical kinetic investigations with a 10-ms time resolution
      adapted to measurements of neuronal receptor function in single cells.
AB  - The gamma-aminobutyric acidA (GABA) receptor belongs to a superfamily of proteins
      involved in chemical reactions that regulate signal transmission between cells of
      the nervous system and is the target of some of the agents most frequently used
      in medicine to control disorders of the central nervous system. In contrast to
      the nicotinic acetylcholine receptor, which initiates signal transmission and is
      the best characterized member of the superfamily, the GABA receptor forms anion
      specific transmembrane channels and inhibits signal transmission. The chemical
      kinetic experiments described here, in which fast chemical reaction techniques
      were used, indicate that both receptor proteins may operate by the same
      mechanism. Also described is the use of a chemical kinetic technique with a 10-ms
      time resolution that we have developed for making measurements with single cells
      isolated from specific areas of the nervous system, in this case the cerebral
      cortex of embryonic mice. A flow device was used to equilibrate receptors on the
      cell surface with GABA, and the concentration of open transmembrane channels in
      the cells was then measured by recording the whole-cell currents at pH 7.2, 21-23
      degrees C, and a transmembrane voltage of -70 mV. Two different receptor forms, A
      alpha and A beta, were detected in cerebral cortical cells. Although the ratio of
      A alpha to A beta varied from cell to cell, on average 35% and 65% of the
      receptor-controlled current was associated with receptor forms A alpha and A
      beta, respectively. At saturating concentrations of GABA, the rate coefficients
      of desensitization, alpha and beta, associated with these two forms have maximal
      values of 4.4 and 0.7 s-1, respectively. The constants of a mechanism that
      accounts for the open transmembrane channels of both receptor forms were
      evaluated over a 50-fold range of GABA concentration. The dissociation constant
      of the site controlling channel opening was 40 microM for A alpha and 320 microM
      for A beta. The channel-opening equilibrium constant, phi-1, was 3.5 for A alpha
      and 20 for A beta. The evaluated constants allow one to calculate Po, the
      conditional probability that at a given concentration of GABA the receptor
      channel is open. Po could also be determined in the presence of 100 microM GABA
      by an independent method in which different assumptions are made in the
      interpretation of the experimental results, the single-channel current-recording
      technique. The value of Po obtained (0.56) was in good agreement with the Po
      value (0.61) calculated for receptor form A alpha from chemical kinetic
      measurements at 100 microM GABA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1377023
TI  - Synthesis and photochemistry of photolabile N-glycine derivatives and effects of
      one on the glycine receptor.
AB  - Three photolabile precursors of glycine containing a photosensitive 2-nitrobenzyl
      moiety attached to the amino group have been synthesized. When exposed to
      ultraviolet radiation between 308 and 350 nm, the compounds photolyze to release
      glycine, an important inhibitory neurotransmitter in the central nervous system.
      The identification of glycine as a photolysis product was determined by two
      different methods: separation of the photolyzed sample by thin-layer
      chromatography followed by a reaction with ninhydrin, and recognition of
      derivatized glycine using the Waters pico-tag method in conjunction with high
      performance liquid chromatography. The photolysis of these compounds at 22
      degrees C has been investigated, and the rate of decay of a transient
      intermediate in the reaction, which is assumed to reflect product release, has
      been measured. For N-(alpha-carboxy-2-nitrobenzyl)glycine this decay rate was
      found to be 940 s-1 at pH 6.8 and 600 s-1 at pH 7.5. Additionally, this compound
      was found to exhibit biological activity upon photolysis; cultured mouse spinal
      cord cells containing neuronal glycine receptors were used to detect the glycine
      liberation. The approach adopted here is useful in demonstrating the utility of
      photolabile precursors of neurotransmitters that have the protecting group linked
      to the neurotransmitter through the amino group. The rapid photolysis of such
      compounds to release free neurotransmitter is valuable in gaining access to
      chemical kinetic studies of neurotransmitter receptors. Previously, such studies
      have been limited because the available methods for neurotransmitter delivery did
      not give a sufficiently high time resolution.

PMID- 1377024
TI  - Disulfide bond-coupled folding of bovine pancreatic trypsin inhibitor derivatives
      missing one or two disulfide bonds.
AB  - The disulfide bond-coupled folding and unfolding mechanism (at pH 8.7, 25 degrees
      C in the presence of oxidized and reduced dithiothreitol) was determined for a
      bovine pancreatic trypsin inhibitor mutant in which cysteines 30 and 51 were
      replaced with alanines so that only two disulfides, between cysteines 14 and 38
      and cysteines 5 and 55, remain. Similar studies were made on a chemically
      modified derivative of the mutant retaining only the 5-55 disulfide. The
      preferred unfolding mechanism for the Ala30/Ala51 mutant begins with reduction of
      the 14-38 disulfide. An intramolecular rearrangement via thiol-disulfide
      exchange, involving the 5-55 disulfide and cysteines 14 and/or 38, then occurs.
      At least five of six possible one-disulfide bond species accumulate during
      unfolding. Finally, the disulfide of one or more of the one-disulfide bond
      intermediates (excluding that with the 5-55 disulfide) is reduced giving unfolded
      protein. The folding mechanism seems to be the reverse of the unfolding
      mechanism; the observed folding and unfolding reactions are consistent with a
      single kinetic scheme. The rate constant for the rate-limiting intramolecular
      folding step--rearrangements of other one-disulfide bond species to the 5-55
      disulfide intermediate--seems to depend primarily on the number of amino acids
      separating cysteines 5 and 55 in the unfolded chain. The energetics and kinetics
      of the mutant's folding mechanism are compared to those of wild-type protein
      [Creighton, T. E., & Goldenberg, D. P. (1984) J. Mol. Biol. 179, 497] and a
      mutant missing the 14-38 disulfide [Goldenberg, D. P. (1988) Biochemistry 27,
      2481]. The most striking effects are destabilization of the native structure and
      a large increase in the rate of unfolding.

PMID- 1377026
TI  - Calcium-dependent interaction of chlorpromazine with the chloroplast 8-kilodalton
      CF0 protein and calcium gating of H+ fluxes between thylakoid membrane domains
      and the lumen.
AB  - Earlier work suggested that Ca2+ ions in the chloroplast thylakoid lumen interact
      with thylakoid membrane proteins to produce a proton flux gating structure which
      functions to regulate the expression of the energy-coupling H+ gradient between
      localized and delocalized modes [Chiang, G., & Dilley, R. A. (1987) Biochemistry
      26, 4911-4916]. In this work, one of the phenothiazine Ca2+ antagonists,
      chlorpromazine, was used as a photoaffinity probe to test for Ca(2+)-dependent
      binding of the probe to thylakoid proteins. [3H]Chlorpromazine photoaffinity
      labels thylakoid polypeptides of Mr 8K and 6K, with generally much less label
      occurring in other proteins (some experiments showed labeled proteins at Mr 13K
      15K). More label was incorporated in circumstances where it is expected that Ca2+
      occupies the putative H+ flux gating site, compared to when the gating site is
      not occupied by calcium. The photoaffinity labeling of the 8-kDa protein was also
      influenced by the energization level of the thylakoids (less labeling under H+
      uptake energization). The 8-kDa protein was identified by partial amino acid
      sequence data as subunit III of the thylakoid CF0 H+ channel complex. The partial
      amino acid sequence of the 6-kDa protein (19 residues were determined with some
      uncertainties) was compared to data in the GCG sequence analysis data base, and
      no clear identity to a known sequence was revealed. Neither the exact site of
      putative Ca2+ binding to the CF0 proteolipid nor the site of covalent attachment
      of the chlorpromazine to the CF0 component has been identified. Evidence for
      gating of energy-linked H+ fluxes by the hypothesized Ca(2+)-CF0 gating site came
      from the correlation between Ca(2+)-dependent binding of chlorpromazine to the
      CF0 8-kDa protein with inhibition of light-driven H+ uptake into the lumen but no
      inhibition of H+ uptake into sequestered membrane domains. When conditions
      favored a delocalized delta mu H+ coupling mode, less chlorpromazine was bound to
      the CF0 structure, and much larger amounts of H+ ions were accumulated in the
      lumen. The data support the hypothesis that Ca2+ ions act in concert with the 8
      kDa CF0 protein (and perhaps another protein, the 6-kDa polypeptide?) in a gating
      mechanism for regulating the expression of the energy-coupling H+ gradient
      between localized or delocalized coupling modes.

PMID- 1377025
TI  - Purification of the vesamicol receptor.
AB  - The vesamicol receptor (VR) present in cholinergic synaptic vesicles isolated
      from the electric organ of Torpedo was solubilized in cholate detergent and
      stabilized with glycerol and a phospholipid mixture. The receptor was purified in
      7% yield by hydroxylapatite, wheat germ lectin affinity, DEAE anion-exchange, and
      size exclusion chromatographies based on a [3H]vesamicol binding assay. A final
      specific binding of 4400 pmol/mg of protein was obtained. The cholate-solubilized
      VR complex exhibited variable aggregation states with particle molecular masses
      of 210-3500 kDa in different experiments. The purified VR exhibited very
      heterogeneous electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis with very diffuse protein staining at about 240 kDa. No
      "classical" polypeptide or glycopeptide band was detected. One form of the SV1
      epitope, which is characteristic of cholinergic synaptic vesicle proteoglycan,
      copurified precisely with the VR. The SV2 epitope, which is found in most
      neuronal and endocrine secretory vesicles, also closely purified with the VR.
      Substantially purified VR retained both enantioselectivity for (-)-vesamicol and
      a linked AcCh-binding site. This confirms the allosteric model for the VR in the
      AcCh transporter. The physicochemical properties of the VR and copurification of
      it with the SV1 epitope strongly suggest that the VR is associated with
      cholinergic vesicle proteoglycan. A second proteoglycan that is not associated
      with the VR but which carries the SV1 and SV2 epitopes also was observed.

PMID- 1377027
TI  - Fluorescence-detected assembly of the signal recognition particle: binding of the
      two SRP protein heterodimers to SRP RNA is noncooperative.
AB  - Protein-RNA and protein-protein interactions involved in the assembly of the
      signal recognition particle (SRP) were examined using fluorescence spectroscopy.
      Fluorescein was covalently attached to the 3'-terminal ribose of SRP RNA
      following periodate oxidation, and the resulting SRP RNA-Fl was reconstituted
      into a fluorescent SRP species that was functional in promoting translocation of
      secretory proteins across the membrane of the endoplasmic reticulum. Each of the
      two protein heterodimers purified from SRP elicited a substantial change in
      fluorescein emission upon association with the modified RNA. The binding of
      SRP9/14 to singly-labeled SRP RNA-Fl increased fluorescein emission intensity by
      41% at pH 7.5 and decreased its anisotropy from 0.18 to 0.16. The binding of
      SRP68/72 increased the fluorescein anisotropy from 0.18 to 0.23 but did not alter
      the emission intensity of SRP RNA-Fl. These fluorescence changes did not result
      from a direct interaction between the dye and protein because the fluorescein
      remained accessible to both iodide ions and fluorescein-specific antibodies in
      the complexes. The spectral changes were elicited by specific SRP RNA-protein
      interactions, since (i) the SRP9/14- and SRP68/72-dependent changes were unique,
      (ii) an excess of unlabeled SRP RNA, but not of tRNA, blocked the fluorescence
      changes, and (iii) no emission changes were observed when SRP RNA-Fl was titrated
      with other RNA-binding proteins. Each heterodimer bound tightly to the RNA, since
      the Kd values determined spectroscopically and at equilibrium for the SRP9/14 and
      the SRP68/72 complexes with SRP RNA-Fl were less than 0.1 and 7 +/- 3 nM,
      respectively. The binding affinity of SRP68/72 for SRP RNA-Fl was unaffected by
      the presence of SRP9/14, and hence the binding of the heterodimers to SRP RNA is
      noncooperative in the absence of SRP54 and SRP19. The SRP protein heterodimers
      therefore associate randomly and independently with SRP RNA to form domains in
      the particle that are distinct both structurally and functionally. Any
      cooperativity in SRP assembly would have to be mediated by SRP54 and/or SRP19.

PMID- 1377028
TI  - Ruthenium red affects the intrinsic fluorescence of the calcium-ATPase of
      skeletal sarcoplasmic reticulum.
AB  - We have studied the effect of Ruthenium red on the sarcoplasmic reticulum Ca(2+)
      ATPase. Ruthenium red does not modify the Ca2+ pumping activity of the enzyme,
      despite its interaction with cationic binding sites on sarcoplasmic reticulum
      vesicles. Two pools of binding sites were distinguished. One pool (10 nmol/mg) is
      dependent upon the presence of micromolar Ca2+ and may therefore represent the
      high-affinity Ca2+ transport sites of the Ca(2+)-ATPase. However, Ruthenium red
      only slightly competes with Ca2+ on these sites. The other pool (15-17 nmol/mg)
      is characterized as low-affinity cation binding sites of sarcoplasmic reticulum,
      distinct from the Mg2+ site involved in the ATP binding to the Ca(2+)-ATPase. The
      interaction of Ruthenium red with these low-affinity cation binding sites, which
      may be located either on the Ca(2+)-ATPase or on surrounding lipids, decreases
      tryptophan fluorescence level of the protein. As much as 25% of the tryptophan
      fluorescence of the Ca(2+)-ATPase is quenched by Ruthenium red (with a
      dissociation constant of 100 nM), tryptophan residues located near the bilayer
      being preferentially affected.

PMID- 1377029
TI  - Complete determination of disulfide bonds localized within the short consensus
      repeat units of decay accelerating factor (CD55 antigen).
AB  - Decay accelerating factor (DAF) has 4 SCR (short consensus repeat) units. Each
      SCR unit consists of approx. 60 amino acids characterized by having four
      conserved cysteine residues and several other highly conserved residues which
      include proline, tryptophan, tyrosine/phenylalanine and glycine. To determine the
      disulfide-bonding pattern, we used the urine form of DAF. After thermolysin and
      trypsin digestion, we isolated seven disulfide-linked peptides by HPLC
      purification. Because all of the cysteine residues are disulfide-bonded, DAF
      should contain eight disulfide bonds. After subtilisin and trypsin digestion, we
      isolated the eighth disulfide-bonded peptides by HPLC purification. From sequence
      analyses of these peptides, we could identify all disulfide bonds in the 4 SCR
      units of DAF as being between the first and the third and between the second and
      the fourth half-cystines within each SCR unit.

PMID- 1377030
TI  - In vivo potentiation of ricin toxicity by monensin delivered through liposomes.
AB  - Monensin, a carboxylic ionophore, which is known to raise intravesicular pH, was
      intercalated in liposomes and its effect on the toxicity of ricin in mice was
      studied. The toxicity of ricin in vivo was found to be significantly enhanced by
      the administration of monensin intercalated in liposomes (liposomal monensin).
      The observed enhancement of the toxicity of ricin by monensin was highly dose
      dependent and was maximal when ricin was injected within 60 min of monensin
      injection. The survival time was found to be reduced in the range of 8-20 h,
      depending on the dose of ricin used, by liposomal monensin. Stability of
      liposomes containing monensin as inferred from the release of entrapped calcein
      or FITC-dextran under both in vivo and in vitro conditions was comparable to that
      observed for liposomes without monensin. Liposomal monensin remains in
      circulation for 2 h and was cleared from the blood stream after 4 h. In contrast,
      15 min was required for the clearance of monensin when administered in free form.
      Studies on the distribution of liposomal monensin and 125I-ricin in various
      tissues have revealed that monensin is mainly localized in the liver and spleen
      which are also the major sites for ricin accumulation. Our observation on the
      substantial enhancement of ricin toxicity in vivo by liposomal monensin strongly
      supports the potential usefulness of the latter as a potentiating agent in the
      enhancement of the toxicity of immunotoxin or hormonotoxin for selective
      elimination of cancer cells.

PMID- 1377031
TI  - Nucleotide sequence of rat vascular cell adhesion molecule-1 cDNA.
AB  - Vascular cell adhesion molecule 1 (VCAM-1) is an inducible transmembrane protein
      which is expressed by vascular endothelium following cytokine activation. VCAM-1
      mediated the adhesion of certain blood leukocytes and tumor cells via the
      interaction with its counter-receptor, the integrin VLA4. When initially cloned
      from interleukin-1 (IL-1) stimulated human umbilical vein endothelial cells, VCAM
      1 was reported to contain six immunoglobulin-like domains. However, subsequent
      cDNA clones and structural analysis of the human gene evealed an alternatively
      spliced seventh immunoglobulin domain. This seven domain form appears to be the
      predominant transcript in IL-1 activated endothelium. In this report, the cloning
      and nucleotide sequence of rat VCAM-1 is described.

PMID- 1377032
TI  - Regulation of chloride transport in cultured normal and cystic fibrosis
      keratinocytes.
AB  - Cultured normal (N) cystic fibrosis (CF) keratinocytes were evaluated for their
      Cl(-)-transport properties by patch-clamp-, Ussing chamber- and isotopic efflux
      measurements. Special attention was paid to a 32 pS outwardly rectifying Cl-
      channel which has been reported to be activated upon activation of cAMP-dependent
      pathways in N, but not in CF cells. This depolarization-induced Cl- channel was
      found with a similar incidence in N and CF apical keratinocyte membranes.
      However, activation of this channel in excised patches by protein kinase (PK)-A
      or PK-C was not successful in either N or CF keratinocytes. Forskolin was not
      able to activate Cl- channels in N and CF cell-attached patches. The Ca(2+)
      ionophore A23187 activated in cell-attached patches a linear 17 pS Cl- channel in
      both N and CF cells. This channel inactivated upon excision. No relationship
      between the cell-attached 17 pS and the excised 32 pS channel could be
      demonstrated. Returning to the measurement of Cl- transport at the macroscopic
      level, we found that a drastic rise in intracellular cAMP induced by forskolin
      did in N as well as CF cells not result in a change in the short-circuit current
      (Isc) or the fractional efflux rates of 36Cl- and 125I-. In contrast, addition of
      A23187 resulted in an increase of the Isc and in the isotopic anion efflux rates
      in N and CF cells. We conclude that Cl(-)-transport in cultured human
      keratinocytes can be activated by Ca2+, but not by cAMP-dependent pathways.

PMID- 1377034
TI  - Surface-reactive biomaterials in osteoblast cultures: an ultrastructural study.
AB  - The tissue/biomaterial interface reactions of three biomaterials selected as
      candidates for hard tissue replacement were studied at the electron microscopical
      level after incubation with enzymatically isolated rat bone cells. An electron
      dense layer was routinely observed between hydroxyapatite, coral, cytodex polymer
      and the neighbouring cells. This layer was visible before bone formation
      occurred, and was collagen free. The ultrastructural features revealed a needle
      shaped filamentous layer continuous with coral material, whereas hydroxyapatite
      or cytodex/tissue interface was granular in appearance. These different
      structures may indicate reactive surfaces, depending on the composition of the
      substrate.

PMID- 1377033
TI  - Neonatal B lymphocyte subpopulations and method of delivery.
AB  - We studied four groups of healthy term newborn infants: (1) 11 infants born by
      vaginal delivery; (2) 11 infants born by elective cesarean section; (3) 10
      infants born by emergency cesarean section with labor, and (4) 10 infants born by
      complicated vaginal delivery. Total and differential leukocyte counts, cortisol
      blood level, and B lymphocyte subpopulations (SmIg, sIgD, sIgM, CD19, CD20, CD21,
      CD23) were evaluated in cord blood samples from the four infant groups.
      Furthermore, the Pentothal blood level was measured in infants born by elective
      cesarean section and in their mothers at delivery. Higher total and differential
      leukocyte counts and cortisol blood levels were observed in group 1 and 4 infants
      as compared with group 2 and 3 infants. A significant correlation was observed
      between cortisol blood level and leukocyte counts. The percentages of positivity
      to cell surface markers of B lymphocyte subpopulations were significantly higher
      in infants born by elective cesarean section. A negative significant correlation
      of thiopentone with sIgM and CD21 was observed. These data indicate a significant
      influence of method of delivery and of thiopentone on B lymphocyte
      subpopulations.

PMID- 1377036
TI  - High-dose aprotinin in cardiac surgery: three years' experience in 1,784
      patients.
AB  - The effect of the proteinase-inhibitor aprotinin on blood loss and homologous
      blood requirement in cardiac surgery was investigated. In a prospective study,
      902 adult patients were treated with high-dose aprotinin (total greater than 5 x
      10(6) kallikrein inactivator units [KIU]; group A), while 882 patients without
      aprotinin administration served as the controls (group C). Both groups were
      operated on between January 1987 and October 1989, and included patients with
      primary coronary artery bypass grafting (n = 525 group C, n = 560 group A), valve
      replacement (n = 292 group C, n = 264 group A), or combined procedures (n = 65
      group C, n = 78 group A), as well as cardiac reoperations (n = 91 group C, n =
      110 group A). The average blood loss 36 hours postoperatively in the aprotinin
      group was 679 +/- 419 mL, compared with 1,038 +/- 671 mL in the control group (P
      less than 0.05). Total homologous blood requirement was also significantly less
      in group A (942 +/- 1,630 mL) compared with group C (1,999 +/- 2,283 mL) (P less
      than 0.05), a reduction of 53%. Serum creatinine concentrations did not show
      intergroup differences on the first postoperative day (group A, 1.2 +/- 0.7;
      group C, 1.3 +/- 0.5 mg/dL) or on discharge from the intensive care unit (ICU).
      Thus, impairment of renal function as a consequence of aprotinin treatment was
      not observed. Three patients developed signs of mild circulatory depression after
      injection of aprotinin, which responded promptly to vasopressor therapy.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377035
TI  - Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose
      aprotinin versus autologous fresh whole blood transfusion.
AB  - Ninety patients undergoing cardiac surgery were randomly divided into three
      groups of 30 patients to compare the effects on bleeding and transfusion
      requirements of either intraoperative infusion of high-dose aprotinin (GpI) or
      reinfusion of autologous fresh whole blood (GpII) versus a control group (GpIII).
      Standardized anesthetic, perfusion, and surgical techniques were used. Platelet
      counts, hemoglobin concentration, hematocrit, fibrinogen, and Ivy-Nelson bleeding
      times determined at fixed times perioperatively did not differ among the three
      groups. The total loss from the chest drains was significantly reduced in GpI
      (328 +/- 28 mL; mean +/- SEM) as compared with the loss in GpII and GpIII (775 +/
      75 mL and 834 +/- 68 mL, respectively). There was a threefold difference in the
      total hemoglobin loss (GpI, 14.2 +/- 1.7 g; GpII, 50.1 +/- 5.0 g; GpIII, 45.0 +/-
      5.2 g). GpI patients also received less banked blood: 250 +/- 53 mL versus 507 +/
      95 mL in GpII and 557 +/- 75 mL in GpIII. No GpI patient required transfusion of
      platelets or fresh frozen plasma. Fresh whole autologous blood transfusions had
      no significant hemostatic effect and failed to reduce the homologous blood
      requirement. Conversely, high-dose aprotinin reduced blood loss and transfusion
      requirements.

PMID- 1377037
TI  - Epidural anesthesia in patients with palliated cyanotic congenital heart disease.

PMID- 1377038
TI  - FK 506 associated disorders in liver transplantation.
AB  - Immunosuppressive regimens are usually required for patients receiving organ
      transplants. The development of a post-transplant lymphoproliferative disorder is
      an infrequent complication of such therapy. FK 506 is a new immunosuppressant
      agent that has recently been used in patients receiving organ transplantation.
      This report describes a 20 month old Saudi child who developed post-transplant
      lymphoproliferative disorder while receiving FK 506 following liver
      transplantation. Such a complication has been recognized with cyclosporine but
      has not been well addressed as yet with FK 506. The child also developed
      progressive renal complications. There was also a difficulty in interpreting the
      results for IgM antibodies to different viruses. The overall features of
      progressive renal toxicity and those of lymphadenopathy, hepatosplenomegaly,
      fever, neutropenia and thrombocytopenia reversed following discontinuation of FK
      506 therapy. It is concluded that all the above complications, though reversible,
      may well be linked to the new immunosuppressant agent FK 506.

PMID- 1377039
TI  - Differential lectin reactivities of alpha-fetoprotein in hepatocellular
      carcinoma: diagnostic value when serum alpha-fetoprotein levels are slightly
      raised.
AB  - The specificity and sensitivity of alpha-fetoprotein (AFP) binding to
      Concanavalin-A (Con-A) and Lens culinaris agglutinin (LCA) in 26 South African
      blacks with advanced symptomatic hepatocellular carcinoma (HCC) but only slightly
      raised serum AFP concentrations (20-500 ng/mL) was compared with that in patients
      with similar serum AFP levels from diseases that might be mistaken clinically for
      HCC (seven 'benign' liver disease [BLD] patients and six with metastatic liver
      disease [MLD] from gastrointestinal tumours). Con-A-Sepharose-4B affinity
      chromatography did not differentiate between the different groups: fucosylation
      rations for the HCC patients were 0.81 +/- 0.60, compared with 0.63 +/- 0.27 and
      0.54 +/- 0.32 in patients with BLD and MLD, respectively. Electrophoresis of AFP
      serum and fraction in the presence or absence of Con-A and LCA showed an increase
      in the AFP C2 band. Rank correlation analysis of the AFP L2 and L3 bands combined
      could distinguish between patients with HCC and other hepatic diseases (P less
      than 0.05).

PMID- 1377040
TI  - pH transients due to monosynaptic activation of GABAA receptors in rat
      hippocampal slices.
AB  - Extracellular pH transients were evoked in rat hippocampal brain slices by
      activation of a monosynaptic inhibitory pathway following pharmacological
      blockade of glutaminergic transmission. Repetitive stimulation in stratum
      radiatum near the recording site in stratum pyramidale evoked an immediate
      alkaline shift which was potentiated by pentobarbital and blocked by picrotoxin
      but not by 2-hydroxy-saclofen. Benzolamide, a poorly permeant inhibitor of
      carbonic anhydrase (CA), and prontosil-dextran 5000, a macromolecular CA
      inhibitor, abolished the alkaline transients evoked by stimulation and by
      exogenous GABA. Thus an extracellular CA is involved in regulating interstitial
      pH in brain, and the stimulation-induced alkaline transients are caused by net
      influx of CO2 into CA1 neurons in response to efflux of bicarbonate across
      postsynaptic GABAA receptor channels.

PMID- 1377041
TI  - Enkephalin-immunoreactive nociceptive neurons in the cat spinal cord.
AB  - In this combined electrophysiological-ultrastructural study in the cat spinal
      cord, we detected enkephalin-like immunoreactivity using internally radio
      labelled monoclonal antibodies in functionally characterized neurons which had
      been filled intracellularly with horseradish peroxidase. Of the 4 neurons
      included in this study, two were positive for enkephalin immunoreactivity; one
      was a nociceptive specific neuron in lamina I, the other a wide dynamic range
      neuron in lamina V. The other two cells were devoid of immunoreactivity for
      enkephalin; one was a wide dynamic range neuron and the other was a non
      nociceptive neuron. These results thus provide a morphological substrate within
      the spinal dorsal horn for the release of an endogenous opioid following
      administration of substance P or noxious cutaneous stimulation.

PMID- 1377042
TI  - Is the nucleus corticalis of teleosts a new cholinergic central nervous system
      for vertebrates?
AB  - Acetylcholinesterase histochemistry suggests that the pretectal nucleus
      corticalis of teleost fish may be cholinergic. Because immunohistochemical
      analysis with antibodies against choline acetyltransferase provides a more
      reliable means of recognizing cholinergic central nervous structures, we
      investigated transverse brain sections of the African cichlid fish, Hemichromis
      lifalili and Hemichromis guttatus, with standard immunohistochemical techniques
      and found the nucleus corticalis to contain choline acetyltransferase. This
      supports the hypothesis that teleosts (unlike all other known vertebrates) have a
      cholinergic second-order sensory (i.e. visual) circuit.

PMID- 1377043
TI  - Computer simulation of the pacemaker oscillations of thalamocortical cells.
AB  - Computer simulations of the spontaneous pacemaker oscillations observed in
      thalamocortical (TC) cells were performed using a biophysical model that included
      the low voltage activated, Ca2+ current, IT, and the mixed Na+/K+, inward
      rectifying current, Ih. The simulations accurately reproduced the waveform and
      voltage-dependence of the pacemaker oscillations, hence the transition from tonic
      firing to burst firing which is a peculiar feature of the electrical activity of
      TC cells both in vivo and in vitro. The results provide further support to the
      suggestion that IT and Ih are essential for the presence of the pacemaker
      oscillations, and indicate that our model is a useful tool for the study of
      spontaneous, low-frequency oscillatory activities in TC cells.

PMID- 1377044
TI  - [Immunoenzyme analysis of antigen-specific determination of HBsAG-containing
      circulating immune complexes (CIC HBsAG/IgM and CIC HBsAG/IgG) in blood serum of
      patients with HBV-infection].
AB  - A complex enzyme immunoassay (ELISA) has been designed for antigen-specific
      determination of HBsAg-containing circulating immune complexes (CIC HBsAg/IgM and
      CIC HBsAg/IgG) in human blood sera in parallel with registration of free HBsAg
      and specific antibodies to viruses of hepatitis A, B and D. It is shown that
      effective formation of HBsAg-containing CIC serologically is registered
      predominantly as a mutually incompatible marker with detection of free HBsAg (in
      70-85% of the cases). CIC HBsAg/IgM and CIC HBsAg/IgG may be registered both in
      parallel and as mutually exclusive markers. Effective formation of HBsAg
      containing CIC in the presence of anti-HBsAg occurs in case of a mild course of
      viral hepatitis of epidemic and sporadic type, while in severe forms of VH-free
      HBsAg is predominantly detected thus pointing either to ineffective formation of
      HBsAg-containing CIC or to their continuous registration with demonstration of
      the effect of delay of witching of anti-HBsM over to anti-HBsG (or CIC HBsAg/IgM
      to CIC HBsAg/IgG). It was also found that in case of epidemic VH in Tajik SSR
      (1987) serologically marked as VH both A and B convalescent phase was
      characterized by parallel disappearance (or lowering of the titer levels) of
      HBsAg-containing CIC and class M antibodies to both hepatitis A (anti-HAV M) and
      B (anti-HBcM, anti-HBsM) along with the containing parallel registration of
      relevant G-antibodies (anti-HAV G/anti-HBcG). This observation requires further
      studies both in terms of close association of viruses of hepatitides A and B and
      with regards to possible antigenic mimicry.

PMID- 1377045
TI  - [Interactions of interferon with other immunomodulators in the regulation of
      human natural killer cell activity].
AB  - The cytotoxic activity of natural killer (NK) cells isolated from peripheral
      blood of 20 healthy donors and 34 patients with multiple sclerosis (MS) against
      labelled with H3-uridine target cells K-562 before and after their 1 hr treatment
      with reaferon (RF), T-activin (TA), myelopid (MP), opioid preparation dalargin
      (DL) as well as with combinations of TA, MP and DL with RF was studied in 14 hrs
      cytotoxic test. It has been shown that combination of RF with TA, MP and DL
      changed the regulatory action of these peptides on NK cell activity in healthy
      donors in vitro. The same combination of the preparations in patients with MS
      caused another changes in regulation of NK activity by them because NK cells in
      MS patients had had initially changed sensitivity to action of these regulatory
      polypeptides.

PMID- 1377047
TI  - P-selectin mediates Ca(2+)-dependent adhesion of activated platelets to many
      different types of leukocytes: detection by flow cytometry.
AB  - Previous studies have shown that thrombin-activated platelets interact through
      the P-selectin with neutrophils and monocytes. To identify other types of
      leukocytes capable of such an interaction, eosinophils, basophils, and
      lymphocytes were isolated from whole blood. Binding of these cells to activated
      platelets was examined in a double immunofluorescence assay and the results show
      that activated platelets not only bind to neutrophils and monocytes, but also to
      eosinophils, basophils, and subpopulations of T lymphocytes. Using monoclonal
      antibodies (MoAbs) specific for subsets of T cells, we could further demonstrate
      that the T cells which bind activated platelets are natural killer (NK) cells and
      an undefined subpopulation of CD4+ and CD8+ cells. All these interactions were
      dependent on divalent cations and were completely inhibited by an MoAb against P
      selectin. Thus, P-selectin mediates the binding of activated platelets to many
      different types of leukocytes. Studies with leukocytes treated with proteases or
      neuraminidase have shown that the structures recognized by P-selectin are
      glycoproteins carrying sialic acid residues. Because the loss of binding of
      activated platelets to neuraminidase-treated neutrophils was almost complete, but
      only partial to treated eosinophils, basophils, and monocytes, the latter cell
      types may have different P-selectin ligands in addition to those present on
      neutrophils. We found that two previously identified ligands for P-selectin, the
      oligosaccharides Le(x) and sialyl-Le(x), had little or no inhibitory effect on
      adhesion of activated platelets to leukocytes and that binding was not inhibited
      by MoAbs against these oligosaccharides. In addition, there was no correlation
      between the expression of Le(x) on several cell types and their capacity to bind
      activated platelets. In contrast, the expression of sialyl-Le(x) on cells was
      almost perfectly correlated with their ability to bind activated platelets. Thus,
      while Le(x) cannot be a major ligand for P-selectin, a possible role for sialyl
      Le(x) in P-selectin-mediated adhesion processes cannot be dismissed. Finally,
      activated platelets were found to bind normally to monocytes and neutrophils of
      patients with paroxysmal nocturnal hemoglobulinuria (PNH) and to neutrophils from
      which phosphatidyl inositol (PI)-linked proteins had been removed by
      glycosylphosphatidyl inositol-specific phospholipase C (GPI-PLC) digestion. This
      suggests that at least part of the P-selectin ligands on these cells are not GPI
      anchored.

PMID- 1377046
TI  - Support of human cord blood progenitor cells on human stromal cell lines
      transformed by SV40 large T antigen under the influence of an inducible
      (metallothionein) promoter.
AB  - We describe the development of a human bone marrow (BM) culture system which
      allows study of the interaction of stromal cell lines (SCL) and highly purified
      hematopoietic progenitor cells. Normal BM stromal cells were electroporated with
      a plasmid containing the simian virus 40 (SV40) large T antigen (SV40 T Ag) under
      the control of a synthetic metallothionein promoter (MT4); this construct is
      designated MT4 SV40 T Ag. SCL in which the rate of proliferation could be
      controlled by altering the zinc (Zn) concentration were characterized,
      demonstrating that the SCL were heterogeneous with respect to G-CSF and GM-CSF
      production. Suppression of SCL proliferation on removal of Zn made it possible to
      use these lines in coculture with purified CD34+ progenitor cells from umbilical
      cord blood. The ability to control proliferation of SCL has allowed us to
      maintain the survival and expansion of colony-forming cells in culture for up to
      2 months. These lines have enabled us to test for stromal cell characteristics at
      a clonal level and provided us with a tool to analyze the events leading to
      lineage commitment and hematopoietic differentiation, as demonstrated by
      suppression of hematopoiesis by an antibody directed against the c-kit molecule.

PMID- 1377049
TI  - Infection of hematopoietic progenitor cells by human cytomegalovirus.
AB  - The susceptibility of hematopoietic progenitor cells to infection by human
      cytomegalovirus (HCMV) was investigated using several strains of HCMV, including
      the recombinant strain RC256. RC256 is derived from the laboratory strain Towne
      and contains the Escherichia coli LacZ gene coding for beta-galactosidase (beta
      gal) regulated by an early HCMV promoter. Expression of LacZ allowed the
      detection of HCMV in individual hematopoietic cells. Clonogeneic bone marrow (BM)
      progenitors, including CD34+ cells, could be infected with HCMV and would then
      form normal hematopoietic colonies. By polymerase chain reaction (PCR)
      amplification of DNA, HCMV could be detected in both erythroid and myeloid
      colonies. LacZ activity was observed predominantly in cells of myelomonocytic
      lineage. When cells derived from HCMV-infected progenitors were cocultivated with
      permissive human fibroblasts, infectious virus expressing LacZ was recovered.
      Although no characteristic HCMV cytopathology was observed in BM colonies, high
      virus to cell ratios resulted in a moderate inhibition of colony formation. Since
      infected hematopoietic progenitors can harbor HCMV for weeks and through several
      differentiation steps in culture, we postulate that in vivo these cells may serve
      as a reservoir of latent virus and contribute to HCMV dissemination.

PMID- 1377048
TI  - Platelet dense granule membranes contain both granulophysin and P-selectin (GMP
      140).
AB  - We recently reported the characterization of a platelet granule membrane protein
      of molecular weight (mol wt) 40,000 called granulophysin (Gerrard et al: Blood
      77:101, 1991), identified by a monoclonal antibody (MoAb D545) raised to purified
      dense granule membranes. Using immunoelectron-microscopic techniques on frozen
      thin sections, this protein was localized in resting and thrombin-stimulated
      platelets. In resting platelets, labeled with antigranulophysin antibodies and
      immunogold probes, label was localized to the membranes of one or two clear
      granules per platelet thin section. D545 also labeled dense granules in
      permeabilized whole platelets and isolated dense granule preparations examined by
      whole-mount techniques. Expression of granulophysin on the platelet surface
      paralleled dense granule secretion as measured by 14C-serotonin release under
      conditions in which lysosomal granule release, as measured by beta-glucuronidase
      secretion, was less than 5%. After thrombin stimulation, both the surface
      connected canalicular system and the plasma membrane were labeled, demonstrating
      redistribution of granulophysin associated with degranulation. Double labeling
      experiments with D545 and antibodies to the alpha-granule membrane protein, P
      selectin, demonstrated labeling of both P-selectin and granulophysin on dense
      granule membranes. Distribution of both proteins on the plasma membrane after
      platelet stimulation was similar. The results demonstrate that granulophysin is
      localized to the dense granules of platelets and is redistributed to the plasma
      membrane after platelet activation.

PMID- 1377050
TI  - BrdU-Hoechst-ethidium bromide (EB) quenching technique for studying kinetics of
      hematopoiesis.

PMID- 1377051
TI  - Response assessment in chronic lymphocytic leukemia after fludarabine plus
      prednisone: clinical, pathologic, immunophenotypic, and molecular analysis.
AB  - The goals of this study were to evaluate the response to treatment in chronic
      lymphocytic leukemia (CLL) according to clinical, pathologic, immunophenotypic,
      and molecular features, as well as to address the clinical significance of each
      finding. One hundred fifty-nine CLL patients with either advanced Rai stage III
      or IV (81 patients) or progressive Rai stage 0 to II (78 patients) were treated
      with fludarabine (30 mg/m2/d intravenously every day for 5 days) plus prednisone
      (30 mg/m2/d orally daily for 5 days). Thirty-six patients were previously
      untreated. The response rates were 12% complete response (CR), 30% nodular
      complete response (nCR), and 18% partial response (PR). In all patients who
      achieved a complete response (both CR and nCR) less than 30% of nucleated cells
      were lymphocytes on marrow aspirate differential analysis; however, nCR patients
      had residual nodular and/or interstitial lymphocyte involvement on marrow biopsy
      examination. There was no evidence of leukemic infiltration on marrow biopsy
      examination in CR patients. With a median follow-up of 35 months, comparison of
      time to progression in the CR and nCR groups at 2 years showed a projected 87%
      versus 55% progression-free survival (P less than .03). Residual disease
      assessment by flow cytometry using simultaneous dual-color staining on blood and
      marrow lymphocytes was also performed on each patient. Residual disease was
      determined by the expression of CD5 on B lymphocytes and the monoclonality of
      surface light-chain expression. After six courses of fludarabine plus prednisone,
      no residual disease was detected by flow cytometry in 89% of the CRs, 51% of the
      nCRs, and 19% of the PRs. Clinical residual disease in PR patients with no
      residual disease detectable by flow cytometry was limited to lymph-adenopathy.
      Time to progression at 2 years was longer in CR and nCR patients having no
      residual disease detected by flow cytometry (84% v 39% 2-year progression-free
      survival, P less than .001). Posttreatment lg gene rearrangement analysis using
      JH, J kappa, and C lambda probes demonstrated no rearranged bands and a return to
      the germline configuration in five of seven CRs and two of eight nCRs studied.
      The molecular studies were concordant with the dual-parameter immunophenotype
      results and none of the patients who reverted to a germline DNA pattern after
      treatment have experienced relapse. The absence of detectable minimal residual
      disease by bone marrow biopsy, dual-color flow cytometry, and lg gene
      rearrangement analysis is achieveable in CLL with fludarabine and is predictive
      of the response duration.

PMID- 1377052
TI  - Does stem cell exhaustion result from combining hematopoietic growth factors with
      chemotherapy? If so, how do we prevent it?

PMID- 1377053
TI  - Erythropoietin rapidly induces tyrosine phosphorylation in the human
      erythropoietin-dependent cell line, UT-7.
AB  - UT-7 is a human megakaryoblastic cell line capable of growing in interleukin-3,
      granulocyte-macrophage colony-stimulating factor, or erythropoietin (Epo) (Cancer
      Res 51:341, 1991). We used this cell line and a selected Epo-dependent subcell
      line (UT-7/Epo) to study the early signal transduction events induced by Epo.
      When UT-7 cells were exposed to Epo, tyrosine phosphorylation of several proteins
      (with molecular weight equivalent to that of p85, p110, and p145) was observed.
      Protein phosphorylation occurred in both a dose- and time-dependent manner. p85
      showed a marked increase in phosphotyrosine content within 30 seconds; maximal
      phosphorylation was observed at 1 minute. Subsequently, tyrosine phosphorylation
      of p110 and p145 was observed, beginning at 1 minute and reaching plateau at 5
      minutes. The degree of phosphorylation of these three proteins gradually
      decreased thereafter. In addition, in UT-7/Epo cells, Epo induced tyrosine
      phosphorylation of other proteins that were not observed in Epo-induced UT-7
      cells. The concentration of Epo required to induce tyrosine phosphorylation was
      in the same range of concentration required to stimulate cell growth. Epo was
      also able to activate p21ras as measured by exchange of guanosine diphosphate for
      guanosine triphosphate. These data show that tyrosine phosphorylation and P21ras
      activation are early signals in the Epo-induced mitogenic pathway.

PMID- 1377055
TI  - Hematopoietic stem cell depletion by restorative growth factor regimens during
      repeated high-dose cyclophosphamide therapy.
AB  - We studied the effects of six cycles of repeated cyclophosphamide (CTX) therapy
      followed by restorative therapy with either granulocyte-macrophage colony
      stimulating factor (GM-CSF) or G-CSF on the hematopoietic stem cell compartment.
      Stem cell function was assessed by serially transferring bone marrow cells from
      CTX-CSF-treated mice into lethally irradiated recipient mice. Bone marrow cells
      from mice that initially received either G-CSF or GM-CSF after CTX therapy more
      rapidly lost the ability to repopulate the recipient lymphoid organs, showed a
      dramatic loss of hematopoietic progenitors, a more rapid loss of CFU-S capacity,
      and a 40% to 50% reduction in marrow repopulating ability (MRA). Interleukin-1
      (IL-1) appeared to have little effect on the CTX-treated mice when used alone.
      However, when administered before the CTX-CSF regimen, IL-1 prevented the stem
      cell depletion as determined by CFU-C, CFU-S, and MRA through the serial
      transplantation procedures. These results support the hypothesis that repeated
      treatments with myelosuppressive drugs followed by stimulation with the CSFs may
      induce damage to the host stem cell compartment, and further suggest that
      pretreatment with IL-1 before CTX therapy may prevent this stem cell damage.

PMID- 1377054
TI  - Blasts from patients with acute myelogenous leukemia express functional receptors
      for stem cell factor.
AB  - Stem cell factor (SCF) acts in concert with lineage-specific growth factors to
      stimulate the growth of hematopoietic colonies. To determine if neoplastic human
      hematopoietic cells would also respond to SCF, we cultured marrow mononuclear
      cells from 20 patients with newly diagnosed acute myelogenous leukemia (AML) and
      two normal donors with SCF, interleukin 3 (IL-3), granulocyte-macrophage colony
      stimulating factor (GM-CSF), or combinations of growth factors in semisolid
      medium, and assessed colony growth. SCF receptors (c-kit receptors) were
      quantitated by equilibrium binding studies with 125I-SCF, and binding parameters
      were estimated using the ligand program. The cellular distribution of c-kit
      receptors was determined by autoradiography. Our results show that SCF alone or
      in combination with IL-3 or GM-CSF increased both the number and size of colonies
      in 10 of the patients. Receptors for SCF were identified on the blasts from all
      20 AML patients. The number of receptors ranged from 600 to 29,000 per cell. In
      the majority of patients, both high- and low-affinity binding sites were
      identified. Neither the number of receptors per cell nor the finding of one or
      two classes of receptors correlated with growth response to SCF. Autoradiographic
      analysis of 125I-SCF binding to normal marrow mononuclear cells revealed grains
      associated with blasts and megakaryocytes. Grain counts on blasts from 10 AML
      patients and on normal marrow blasts suggested that high-affinity c-kit receptor
      expression on AML blasts is lower than or similar to that of normal blasts. These
      results identify c-kit receptors on human AML blasts, and indicate that SCF acts
      synergistically with IL-3 or GM-CSF to stimulate colony growth from the marrow
      cells of a portion of patients with AML.

PMID- 1377056
TI  - Functional reconstitution of the human interleukin-3 receptor.
AB  - The high-affinity receptors for human interleukin-3 (IL-3), GM-CSF, and IL-5 are
      composed of alpha and beta subunits. The alpha subunits are primary ligand
      binding proteins specific for each ligand, whereas the three human receptors
      share a common beta subunit (beta c). In contrast to humans mice have two closely
      related genes, AIC2A and AIC2B, which are homologous to human beta c. The AIC2A
      gene encodes a low-affinity murine IL-3 binding protein, and the AIC2B protein is
      the beta subunit shared between murine GM-CSF receptors (mGMR) and IL-5 receptors
      (mIL-5R). To examine the function of these receptor components, we established
      various stable transfectants of murine IL-2-dependent CTLL-2 cells. CTLL-2
      transfectants expressing both the alpha and beta subunits of the human IL-3
      receptor (hIL-3R) proliferated in response to physiologic concentrations of hIL
      3. Coexpression of hIL-3R alpha with AIC2B but not with AIC2A in CTLL-2 cells
      conferred a growth response to hIL-3. Although CTLL-2 transfectants expressing
      hIL-3R alpha alone did not proliferate in the presence of hIL-3, hIL-3-responsive
      sublines were repeatedly isolated. These sublines expressed endogenous AIC2B but
      not AIC2A. These results indicate that human beta c is essential for hIL-3
      signaling and that AIC2B is a murine equivalent of human beta c. We also showed
      that hIL-3 and hGM-CSF induced tyrosine phosphorylation of several proteins in
      CTLL transfectants, similar to those observed in human factor-dependent TF-1
      cells stimulated with hIL-3 and hGM-CSF.

PMID- 1377057
TI  - Effect of stem cell factor with and without granulocyte colony-stimulating factor
      on neonatal hematopoiesis: in vivo induction of newborn myelopoiesis and
      reduction of mortality during experimental group B streptococcal sepsis.
AB  - Neonatal hematopoiesis and host defense are developmentally immature and under
      states of increased demand predispose the newborn to peripheral cytopenias and
      depletion of bone marrow storage pool reserves. We have previously demonstrated
      that recombinant human granulocyte colony-stimulating factor (rhG-CSF) can
      significantly modulate neonatal rat granulopoiesis and act synergistically with
      antibiotic therapy to reduce the mortality rate during experimental group B
      streptococcal sepsis. Stem cell factor (SCF) has been shown to stimulate early
      hematopoietic progenitor cells and, in the presence of lineage-specific CSFs,
      enhance committed progenitor cell proliferation. In the present study we examined
      the in vivo neonatal hematologic effects of recombinant rat (rr) SCF (14 days),
      simultaneous rrSCF + rhG-CSF (14 days), and sequential combination of rrSCF (7
      days) + rhG-CSF (7 days). Sprague-Dawley newborn rats (less than or equal to 24
      hours) were injected intraperitoneal (IP) x 14 days with the above combinations.
      rrSCF (0 to 200 micrograms/kg/d) had a negligible effect on the peripheral
      platelet count and absolute neutrophil count (ANC) but the diminution in the
      hematocrit during the first 10 days of treatment was less pronounced (P = .0001).
      However, the simultaneous use of rrSCF + rhG-CSF synergistically increased the
      circulating day 6 to 13 ANC (P = .001). Similarly, sequential rrSCF + rhG-SCF
      also had a synergistic significant effect during the second week of therapy on
      the circulating ANC (P = .01). The bone marrow neutrophil storage and
      proliferative pools were also significantly increased in newborn rats treated
      with rrSCF + rhG-CSF versus rhG-CSF (P = .02). The bone marrow and liver/spleen
      CFU-GM pool was unchanged; however, the CFU-GM proliferative rates were
      significantly increased in the rrSCF + rhG-CSF group (P = .04). rrSCF also
      induced a significant increase in the bone marrow and liver/spleen mast cell pool
      (P = .002). Lastly, rrSCF x 14 days +/- rhG-CSF significantly reduced the
      mortality rate at 48 and 120 hours after experimental group B streptococcus
      sepsis (P = .03 and .05, respectively). These data suggest that combination SCF +
      G-CSF therapy compared with G-CSF alone significantly increases the neonatal rat
      peripheral neutrophil count, bone marrow myeloid pools and proliferative rates,
      and induces a reduction in the mortality rate during experimental bacterial
      sepsis. SCF therapy may have future potential applications in the modulation of
      human neonatal hematopoiesis and host defense.

PMID- 1377059
TI  - Intermediate filaments in Sertoli cells.
AB  - Using immunohistochemical techniques both at light and electron microscopic
      levels, the arrangement and distribution of intermediate filaments in Sertoli
      cells of normal testis (in rat and human), during pre- and postnatal development
      (in rabbit, rat, and mouse) and under experimental and pathological conditions
      (human, rat), have been studied and related to the pertinent literature.
      Intermediate filaments are centered around the nucleus, where they apparently
      terminate in the nuclear envelope providing a perinuclear stable core area. From
      this area they radiate to the plasma membranes; apically often a close
      association with microtubules is seen. Basally, direct contacts of the filaments
      with focal adhesions occur, while the relationship to the different junctions of
      Sertoli cells is only incompletely elucidated. In the rat (not in human) a group
      of filaments is closely associated with the ectoplasmic specializations
      surrounding the head of elongating spermatids. Both in rat and human, changes in
      cell shape during the spermatogenic cycle are associated with a redistribution of
      intermediate filaments. As inferred from in vitro studies reported in the
      literature, these changes are at least partly hormone-dependent (vimentin
      phosphorylation subsequent to FSH stimulation) and influenced by local factors
      (basal lamina, germ cells). Intermediate filaments, therefore, are suggested to
      be involved in the hormone-dependent mechanical integration of exogenous and
      endogenous cell shaping forces. They permit a cycle-dependent compartmentation of
      the Sertoli cell into a perinuclear stable zone and a peripheral trafficking zone
      with fluctuating shape. The latter is important with respect to the germ cell
      supporting surface of the cell which seems to limit the spermatogenetic potential
      of the male gonad.

PMID- 1377058
TI  - No effect of growth hormone treatment on axonal transport of slow component a in
      diabetic and nondiabetic rats.
AB  - A decreased axonal transport of slow component a (SCa), i.e., neurofilaments, is
      an early event in experimental diabetes as well as hypothyroidism, and common to
      these metabolic derangements are decreased levels of serum insulin-like growth
      factor I (IGF-I). To evaluate the possible connection between these facts, we
      investigated the effect of growth hormone (GH), which stimulates IGF-I
      production, on axonal transport of SCa in diabetic and nondiabetic rats. Serum
      concentrations of IGF-I fell from about 1500 micrograms/L in controls to about
      600 micrograms/L in diabetics. GH treatment (100 mu/rat twice daily) normalized
      IGF-I for the first week of diabetes, after which the level decreased to the
      level of the untreated diabetics. The SCa transport velocity was found to be
      decreased in the diabetic nerves as previously reported [0.91 +/- 0.07 = mm/day,
      n = 9; (mean +/- SD) versus 1.01 +/- 0.09 mm/day, n = 8, in controls, 2 p less
      than 0.05). No changes were seen for the GH-treated groups (1.03 +/- 0.06 mm/day,
      (n = 11) in GH-treated controls). The lack of effect of GH treatment can be due
      to blockage of IGF-I synthesis or the decreased level of thyroid hormone,
      triiodothyronine (T3), in the diabetic rats.

PMID- 1377060
TI  - Comparison of alcian blue and ruthenium red effects on preservation of outer
      envelope ultrastructure in methanotrophic bacteria.
AB  - Alcian blue (AB) and ruthenium red (RR) effects on ultrastructural preservation
      of the bacterial cell envelope of methanotrophs are compared. A previous
      successful method with RR that enhanced preservation of outer envelope layers in
      two representative methanotroph species is applied to other genera and species of
      methanotropic bacteria. Alcian blue is substituted for RR in this en bloc
      protocol. The effect of AB on preservation of these layers is assessed at the
      ultrastructural level and compared to RR for all species examined. Further,
      comparison with freeze etch and a fixation in the absence of either RR or AB is
      made. Both RR and AB are found to aid preservation and help visualize additional
      components of the cell envelope which are lost or minimized in a standard
      fixation not employing these cationic reagents. For some species, images obtained
      are similar between RR and AB procedures and agree with images seen by freeze
      etch. For other species, AB preserves extended filamentous material that is
      partially condensed even with the use of RR. Thus, use of AB improves the
      preservation of outer envelope structure in these organisms equally or more
      effectively than use of RR.

PMID- 1377061
TI  - Successful treatment of primary gastric non-Hodgkin's lymphoma with chemotherapy
      and radiotherapy.
AB  - A case of primary gastric lymphoma is reported. The lymphoma was of the diffusely
      infiltrating type extending from the supraangular region to the prepyloric region
      of the stomach. The patient refused gastrectomy, therefore combined treatment
      with BACOP chemotherapy and radiotherapy was carried out. Complete remission was
      achieved without any major complications. The patient has remained free from
      relapse for over 20 months.

PMID- 1377062
TI  - Close linkage of retinoic acid receptor genes with homeobox- and keratin-encoding
      genes on paralogous segments of mouse chromosomes 11 and 15.
AB  - Retinoic acid is essential for normal development and growth of structures such
      as head and limbs, and it can act as morphogen or teratogen. Retinoic acid
      induces expression of genes such as the homeobox genes and keratin type I and
      type II genes. Retinoic acid receptors are nuclear transcription factors that
      play a key role in retinoid physiology. As part of the characterization of
      retinoic acid receptor gene family, linkage of genes encoding the three receptors
      was determined by using interspecific backcross and recombinant inbred strain
      analysis of restriction fragment variants. Retinoic acid receptor alpha is
      located on mouse Chromosome (Chr) 11 near the homeobox-2 complex and the keratin
      type I gene complex, whereas retinoic acid receptor gamma is on mouse Chr 15 near
      the homeobox-3 complex and the keratin type II complex. Close genetic proximity
      of these functionally related genes may be significant. We confirmed assignment
      of retinoic acid receptor beta to the centromeric portion of Chr 14. These
      linkage assignments provide further evidence for duplicated segments in the mouse
      genome.

PMID- 1377063
TI  - Induced reciprocal translocation in transgenic mice near sites of transgene
      integration.
AB  - Transgenic mice (JCP0 #18), heterozygous for an insertion of approximately 50
      copies of the rat peripheral myelin (P0) protein cDNA, displayed a pattern of
      reduced litter size that suggested a chromosome rearrangement. Chromosome banding
      studies of fetal cells disclosed the presence of an apparently balanced
      translocation between a Chromosome (Chr) 1 and 14 with breakpoints at bands 1H3
      and 14C3. In situ hybridization of biotin-labeled P0 rat cDNA probe to chromosome
      spreads and detection of specific signal with fluorescein isothiocyanate
      conjugated avidin revealed a strong signal on the 1(14) translocation chromosome
      at the site of the breakpoint. A weaker signal was present near the breakpoint on
      the 14(1) derivative chromosome. These results suggest an etiologic relationship
      between the insertion of the transgene and the origin of the translocation. To
      further elucidate possible mechanisms, we first mapped the endogenous P0 gene
      (gene symbol Mpp). As previously reported (You et al., Genomics 9: 751, 1991), we
      found that Mpp is located on Chr 1 in the region of the translocation breakpoint
      in JCP0 mice. Subsequently, we have carried out pulsed-field gel and standard
      Southern analyses with P0 gene probes, but found no evidence for a direct
      involvement of the endogenous P0 gene in the process that generated the balanced
      reciprocal translocation. Thus, we favor the hypothesis that, during repair of
      DNA strand breakage--possibly induced by the microinjection procedure--the
      transgene copies were ligated to broken ends of Chrs 1 and 14. According to
      convention, this translocation is designated T(1;14)1Po. Homozygotes are
      phenotypically normal and breed well; they will be useful for genetic and
      physical mapping of Chrs 1 and 14.

PMID- 1377064
TI  - Species- and tissue-specific transcription of complex, highly repeated satellite
      like Bsp elements in the fox genome.
AB  - We have studied the transcription of highly repeated satellite-like Bsp elements
      containing the potential promoter boxes for RNA polymerase III in the genomes of
      adult silver and arctic foxes. The Bsp repeat transcripts were abundant enough to
      be detected by Northern blot and semiquantitative dot blot hybridizations, and
      the majority were found in the nuclear RNA fraction from arctic fox kidneys. Weak
      hybridization signals were revealed with the cytoplasmic RNA preparation from
      silver fox kidneys and with the nuclear RNA fraction from arctic fox liver, and
      their intensity was intermediate with the total RNA from arctic fox brain. Taken
      together, the data suggest possible genomic interspersion of some Bsp repeats in
      these two representatives of Canidae. The observed species-and tissue-specificity
      of the transcription of Bsp repeats suggests that they may potentially accomplish
      regulatory functions in the fox genomes.

PMID- 1377065
TI  - Protective activity of inhaled frusemide against immunological respiratory
      changes and mediator release in guinea-pigs.
AB  - The antianaphylactic activity of inhaled frusemide was studied in ovalbumin
      sensitized guinea-pigs. The exposure of the animals to frusemide aerosol (1%
      solution for 20 min) attenuated the respiratory response to ovalbumin challenge
      (aerosol 1% solution) and was associated with a significant reduction of blood
      histamine (70%; P less than 0.01) and thromboxane-B2 (35%; P less than 0.01)
      compared to control animals. Similar results were obtained in isolated lungs
      perfused via the trachea excised from ovalbumin-sensitized guinea-pigs exposed to
      frusemide aerosol (1% solution for 20 min). In this series of experiments
      frusemide significantly prevented the increase in tracheal perfusion pressure
      (45%; P less than 0.01) and the concomitant release into the pulmonary effluent
      of both histamine (75%; P less than 0.01) and thromboxane-B2 (39%; P less than
      0.01). In another series of experiments, frusemide (1 x 10(-4) M) significantly
      reduced the immune release of histamine from mast cells of ovalbumin-sensitized
      rats. The inhibitory activity of frusemide was in the same range of potency (66%;
      P less than 0.01) as that of disodium cromoglycate (1 x 10(-4) M). These data
      taken together indicate that frusemide when given by inhalation prevents
      histamine release secondary to antigen-antibody reaction.

PMID- 1377066
TI  - Influence of nitrovasodilators on bovine pulmonary histamine release.
AB  - The organic nitrates and related nitrovasodilators are relaxants of vascular and
      airway smooth muscle. Very little information is currently available regarding
      the influence of nitrates and related nitrovasodilators on pulmonary autacoid
      release. This study examined the influence of glyceryl trinitrate, isosorbide
      dinitrate and sodium nitroprusside on histamine release from bovine lung mince.
      Spontaneous histamine release from bovine lung mince was not altered by 0.1 nM to
      1 microM glyceryl trinitrate, isosorbide dinitrate or sodium nitroprusside.
      Glyceryl trinitrate, isosorbide dinitrate and sodium nitroprusside produced a
      concentration-dependent decrease in A23187 (10 microM) stimulated histamine
      release. Glyceryl trinitrate also inhibited histamine liberation following the
      addition of compound 48/80. Further studies indicated that the inhibitory action
      of glyceryl trinitrate was reversed by coincubation with the guanylate cyclase
      inhibitor, methylene blue (10 microM). These findings indicate that glyceryl
      trinitrate, sodium nitroprusside and isosorbide dinitrate inhibit non
      immunologically stimulated pulmonary histamine release and suggest that
      alterations in guanylate cyclase activity may influence pulmonary histamine
      release.

PMID- 1377068
TI  - Effects of lindane on growth of cellular slime mold Dictyostelium discoideum.

PMID- 1377067
TI  - Pesticides in marine sediments associated with golf course runoff.

PMID- 1377069
TI  - DNA binding and mutagenicity of lindane and its metabolites.

PMID- 1377070
TI  - [Osteocalcin in diffuse toxic goiter].
AB  - Bone metabolism was investigated in toxic goiter. The authors obtained evidence
      on high levels of osteocalcin which marks bone formation. The time of the thyroid
      function recovery during thyrostatic therapy and indices of phosphorus-calcium
      metabolism disagree indicating delayed normalization of the bone tissue
      metabolism. There is a correlation between the thyroid function, osteocalcin and
      oxyproline that indirectly confirms the action of thyroid hormones on the bone
      matrix; between osteocalcin levels and other indices of bone metabolism (serum
      alkaline phosphatase activity and oxyproline excretion).

PMID- 1377071
TI  - Mechanism of matrix vesicle calcification: characterization of ion channels and
      the nucleational core of growth plate vesicles.

PMID- 1377072
TI  - Suicide and vehicle exhaust emissions.

PMID- 1377073
TI  - In search of the unknown primary.

PMID- 1377074
TI  - Effect of aprotinin on neutrophil function after major vascular surgery.
AB  - High-dose aprotinin reduces blood loss and blood transfusion requirements during
      liver transplantation and cardiac and vascular surgery. The mechanism of the
      haemostatic effect of aprotinin is unclear. A general effect on the anti
      inflammatory response may be involved. Because leucocyte activation is part of
      this process, white cell function was measured in patients undergoing aortic
      surgery who received high-dose aprotinin therapy (n = 10) and was compared with
      the results from controls who did not (n = 10). The test group received an
      intravenous bolus (2 x 10(6) kallikrein inhibitor units) of aprotinin after
      induction of anaesthesia followed by continuous infusion (0.5 x 10(6) kallikrein
      inhibitor units/h) until the end of the operation. Blood samples were obtained
      before operation, immediately after surgery, and 1 and 7 days after operation.
      Aprotinin maintained significantly better postoperative white cell function as
      measured by bipolar shape formation (P less than 0.001), unstimulated nitroblue
      tetrazolium (NBT) reduction (P less than 0.001) and chemotaxis (P less than
      0.001). Endotoxin-stimulated NBT reduction was similar in both groups, indicating
      that neutrophils from treated individuals retained the capacity to respond to
      oxidative stimuli. Aortic surgery activates neutrophils in vivo, as reflected by
      impaired chemotaxis and increased superoxide production. Aprotinin protects the
      cells against this potentially deleterious effect without affecting their ability
      to respond when provoked. Whether this affects leucocyte interaction with
      coagulation pathways and contributes to the reduction in blood loss remains to be
      determined.

PMID- 1377075
TI  - Pantomime, praxis, and aphasia.
AB  - The production and comprehension of pantomimed movements by asphasic subjects
      were studied with respect to their relationship to the aphasic deficit on one
      hand and apraxia on the other. At issue was whether impaired use of pantomime is
      a manifestation of reduced symbolic capacity or purely a manifestation of an
      apraxic impairment of purposeful movement or both. Tests of pantomime included a
      Pantomime Recognition Test, a nonverbal Transitive Pantomime Production Test, and
      an Intransitive Pantomime Production Test (to oral command). Imitation of
      Nonmeaningful Movements served as a measure of apraxia, uncontaminated by
      symbolic or linguistic factors. Imitation of Meaningful Movements taken from the
      pantomime tasks was also tested. Independent measures of auditory comprehension,
      picture naming, and reading comprehension were used as indices of language
      impairment. Intellectual function was measured by the Performance scale of the
      WAIS. Thirty aphasic subjects were examined. Twenty healthy age-matched normals
      served to establish scoring standards for the pantomime tests. Multiple
      regression analysis revealed significant, independent contributions from both
      auditory comprehension and imitation of Nonmeaningful Movements to all of the
      tests of pantomime production and pantomime recognition. All measures of
      pantomime production and pantomime recognition were strongly intercorrelated.
      While the three language measures were strongly correlated with each other,
      auditory comprehension was the only one of them that was significantly and
      consistently related to the pantomime tests. None was related to the imitation of
      nonmeaningful movement. The results are taken as indicating (1) that pantomime
      production and imitation share common factors with both praxis and auditory
      comprehension; (2) apraxia entails impairment of both production and
      interpretation of purposeful movements. Possible theoretical accounts for these
      results are offered.

PMID- 1377076
TI  - Relation of linguistic communication abilities of Alzheimer's patients to stage
      of disease.
AB  - A battery of linguistic communication (L-C) tasks was administered to 152
      Alzheimer's disease patients in different stages of the disease and 60 normal
      elders. Subject performance data are used to construct a profile of L-C deficits
      by disease stage, as determined by ratings on the Global Deterioration Scale.
      Specification also is made of the L-C tasks on which mild Alzheimer's patients
      perform like normal elders, the relative difficulty of various L-C processes, the
      disease stage in which the greatest change occurs in L-C functions, and the
      degree of variation in L-C for individuals at a particular level of dementia
      severity.

PMID- 1377077
TI  - Organization of cutaneous primary afferent fibers projecting to the dorsal horn
      in the rat: WGA-HRP versus B-HRP.
AB  - Primary afferent projections from cutaneous afferents in the forelimb and
      hindlimb digits to the dorsal horn (DH) were examined using 4 tracers: (1) 25%
      free horseradish peroxidase (HRP), (2) 2.5% wheat-germ agglutinin conjugated to
      horseradish peroxidase (WGA-HRP), (3) a mixture of 25% free HRP and 2.5% WGA-HRP
      (WGA-HRP/HRP) or (4) 0.1% HRP conjugated to cholera toxin (B-HRP). The tracer was
      injected intracutaneously into the digits. Three to 4 days later, the rats were
      perfused transcardially, transverse sections (60-microns thick) were cut and the
      HRP was reacted using the tetramethyl benzidine (TMB) method. The location of the
      label was reconstructed by camera lucida drawings. In rats which received an
      injection of HRP alone, no label was detected in the DH. Rats injected with WGA
      HRP had projection patterns similar to those injected with WGA-HRP/HRP. Patterns
      of labelling with WGA-HRP differed markedly from those with B-HRP. WGA-HRP
      labelled cutaneous afferents projecting to Rexed's laminae I-III, with the
      densest label in lamina II; in contrast, B-HRP labelled cutaneous afferents
      projecting to laminae II-V, with the densest label in laminae III-IV. These
      results indicate that, for cutaneous primary afferents projecting to the DH, WGA
      HRP and B-HRP labelled different subpopulations of fibers, with the B-HRP
      labelled subpopulation biased toward afferents of larger diameter.
      Rostrocaudally, the extent of the densest fiber projections, whether labelled by
      WGA-HRP or by B-HRP, was essentially the same, but the extent of the less densely
      labelled projections was much greater with B-HRP than with WGA-HRP. Comparisons
      of the projection maps from each of the five digits, using either WGA-HRP or B
      HRP, indicated that, as seen in transverse sections through the DH, there was
      extensive overlapping among the labelled cutaneous afferent fibers from adjacent,
      or even non-adjacent digits.

PMID- 1377079
TI  - A second auditory area in the non-cortical telencephalon of a reptile.
AB  - Injections of horseradish peroxidase (HRP) into a caudocentral portion of the non
      cortical telencephalon of Caiman known as the dorsolateral area (dorsal
      ventricular ridge) resulted in retrogradely labeled neurons throughout the entire
      extent of the ipsilateral nucleus reuniens. HRP-positive cells were most numerous
      in nucleus reuniens pars diffusa with only sparse labeling of neurons in nucleus
      reuniens pars centralis. The results of the present experiment, when compared
      with those of a prior study that determined the telencephalic connections of
      nucleus reuniens pars centralis, suggested that these two forebrain areas are
      separate. Staining with succinate dehydrogenase and acetylcholinesterase revealed
      that nucleus reuniens pars centralis and pars diffusa and their respective
      telencephalic projection areas can be differentiated on the basis of
      histochemical features. These findings in Caiman suggest that certain thalamic
      and telencephalic auditory areas in birds and crocodilians are most likely the
      result of common ancestry rather than examples of parallel evolution.

PMID- 1377078
TI  - Cooperative regulation of nerve growth factor synthesis and secretion in
      fibroblasts and astrocytes by fibroblast growth factor and other cytokines.
AB  - Acidic fibroblast growth factor (aFGF) enhances nerve growth factor (NGF)
      synthesis by astrocytes obtained from various brain regions. NGF secretion by
      fibrous-shaped astrocytes transformed by dibutyryl-cAMP (db-cAMP) pretreatment
      was less than that by untreated astrocytes. However, aFGF also enhanced NGF
      secretion by fibrous-shaped astrocytes. The effects of various kinds of
      intracellular signaling modulators on NGF synthesis were examined. None of the
      following second messenger effectors had an effect on NGF synthesis: protein
      kinase C (PKC) agonist (phorbol myristate acetate (PMA)) or antagonist
      (sphingosine (SP)). LiCl, and ionomycin (Iono). Further, increases of
      intracellular cAMP by forskolin (FK) or db-cAMP have no significant effect on NGF
      synthesis in astrocytes under a standard culture condition. However, NGF
      synthesis by astrocytes in the presence of aFGF was significantly enhanced by db
      cAMP, but not by FK or sodium butyrate. These results indicate that an excessive
      amount of cAMP enhances the effect of aFGF on NGF synthesis in astrocytes. NGF
      synthesis in astrocytes was not affected by treatment with anti-aFGF or anti-bFGF
      neutralizing antibodies, indicating that FGFs are not involved in the autocrine
      regulation of NGF synthesis in astrocytes. Transforming growth factor-beta 1 (TGF
      beta 1), which inhibits some effects of FGFs, increased NGF synthesis in concert
      with aFGF. Furthermore, the highest NGF synthesis was observed when astrocytes
      were stimulated by all of the following cytokines: aFGF, interleukin-1 beta (IL-1
      beta), tumor necrosis factor-alpha (TNF-alpha) and TGF-beta 1. The mechanism
      regulating NGF synthesis in fibroblasts obtained from prenatal rat skin was also
      investigated. Acidic FGF, basic FGF (bFGF), epidermal growth factor (EGF),
      platelet-derived growth factor (PDGF), transforming growth factor-alpha (TGF
      alpha), TGF-beta 1, IL-1 beta, and TNF-alpha were found to be regulators of NGF
      synthesis in skin fibroblasts. Among these cytokines, aFGF is the most potent
      regulator of NGF synthesis in fibroblasts. NGF synthesis by skin fibroblasts,
      either in the presence or absence of aFGF, was not modified by any of the
      following: FK, PMA, SP, LiCl, and Iono. However, db-cAMP significantly enhanced
      NGF synthesis in both conditions. Sodium butyrate enhanced NGF synthesis in the
      presence of aFGF, but not in the absence of aFGF. These results suggest that an
      excessive amount of cAMP and butyrate moiety regulate NGF synthesis in skin
      fibroblasts in different ways.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1377080
TI  - Effects of intravenous infusion of substance P on arginine vasopressin and
      oxytocin secretion in normal men.
AB  - In order to establish possible stimulatory effects of increasing plasma
      concentrations of substance P (SP) on the arginine vasopressin (AVP) and/or
      oxytocin (OT) secretion, successively increasing doses of SP(0.5, 1 and 1.5
      pmol/kg-1/min-1; each dose for 20 min) were infused in 7 normal men. Plasma AVP
      and OT levels were measured before infusion and every 20 min, just before
      increasing the infusion dose of SP. During tests, SP infusion did not produce
      untoward side effects or changes in blood osmolality and/or pressure. Plasma OT
      levels did not change during SP infusion. Plasma AVP concentrations were not
      modified by the infusion of the lowest dose of SP, whereas they were
      significantly increased in a dose response fashion when higher amounts of SP were
      given. These findings demonstrate for the first time in humans that the systemic
      administration of SP exerts stimulatory effects on AVP, but not on OT secretion.

PMID- 1377082
TI  - Immunocytochemical localization of endopeptidase 24.15 in rat brain.
AB  - Endopeptidase 24.15 (EC 3.4.24.15; EP 24.15), a zinc-metalloendopeptidase highly
      active in rat testes, brain and pituitary, converts some prodynorphin- and
      proenkephalin-derived oligopeptides into the corresponding enkephalins and
      degrades a variety of bioactive peptides including bradykinin, neurotensin, and
      both angiotensin I and II. The immunocytochemical localization of the enzyme was
      studied in rat brain using a polyclonal antibody raised in rabbits against a
      homogeneous preparation of the enzyme isolated from rat testes. The distribution
      of EP 24.15 immunoreactivity in the brain was widespread, being present in both
      neurons and glial cells. Surprisingly, however, staining was predominantly
      nuclear, and not cytoplasmic as expected based on the biochemical demonstration
      that EP 24.15 activity is predominantly associated with the soluble protein
      fraction of brain homogenates. Cytoplasmic staining was detected in large neurons
      but was less intense than the nuclear staining. The highest density of EP 24.15
      staining was detected in nuclei of cerebellar Purkinje cells and in hippocampal
      dentate gyrus cells. High levels of immunoreactivity were also noted in brain
      areas which contain peptides known to be substrates of the enzyme in vitro. This
      localization supports a role for EP 24.15 in neuropeptide metabolism, but also
      suggests an as yet undefined role in nuclear function.

PMID- 1377081
TI  - A prominent epitope on GABAA receptors is recognized by two different monoclonal
      antibodies.
AB  - The monoclonal antibody 62-3G1 raised against the GABAA/benzodiazepine receptor
      complex was tested for its subunit selectivity using recombinantly expressed
      GABAA receptor subunits. The antibody bound selectively to beta 2 and beta 3 but
      not beta 1 nor any other GABAA receptor subunit. Using enzyme-linked
      immunosorbent assay, the epitope on beta 2 and beta 3 subunits was determined to
      be residues 1-3. MAb bd 17, which displays identical subunit selectivity as mAb
      62-3G1, was seen to bind to the same epitope. These results resolve the subunit
      selectivity of mAbs 62-3G1 and bd 17 and reveal the identity and localization of
      a prominent immunogenic epitope on the GABAA/benzodiazepine receptor.

PMID- 1377083
TI  - GABA-like immunoreactive neurons in the retina of Bufo marinus: evidence for the
      presence of GABA-containing ganglion cells.
AB  - gamma-Aminobutyric acid (GABA)-like immunoreactive (IR) neurons in the retina of
      the cane toad Bufo marinus were revealed using immunohistochemistry on retinal
      wholemount preparation and sectioned material. GABA-IR neurons included
      horizontal, bipolar and amacrine cells in the inner nuclear layer and small to
      medium sized cells in the ganglion cell layer. A few IR axons were seen in the
      optic fiber layer of the retina. Following the injection of the carbocyanine dye,
      DiI into the optic tectum ganglion cells were retrogradely filled. A small
      population of DiI-filled ganglion cells (2.8%) was found to be GABA-IR. GABA-IR
      neurons in the ganglion cell layer without DiI label were considered to be
      displaced amacrine cells of which 45.3% were GABA positive. It is proposed that
      GABA-containing ganglion cells may form an inhibitory projection to visual
      centers of the anuran brain.

PMID- 1377084
TI  - Expression of granulocyte colony stimulating factor and granulocyte-macrophage
      colony stimulating factor genes in human astrocytoma cell lines and in glioma
      specimens.
AB  - Expression of granulocyte (G) and granulocyte-macrophage (GM) colony stimulating
      factor (CSF) genes in human cells of astroglial lineage was studied. Primers for
      CSFs were used to analyze RNA transcripts in 5 cultured human astrocytoma cell
      lines and 8 fresh brain specimens by polymerase chain reaction. Constitutive
      expression of mRNA transcripts of GM-CSF could be detected in all astrocytoma and
      one neuroblastoma cell lines, and two out of 5 unstimulated astrocytomas, U87MG
      and U138 MG, expressed G-CSF genes. After stimulation with interleukin (IL)-1
      beta + tumor necrosis factor (TNF)-alpha, all cell lines expressed G-CSF. In
      addition to the cultured cells, we examined gene expression within human
      malignant astrocytoma, peritumoral brain and autopsied normal brains. The results
      show that some of the tumor and its surrounding reactive lesions express G- and
      GM-CSF genes but normal brains do not. The concentration of G- and GM-CSF in
      supernatants of cultured cells was assessed at the protein level by ELISA. A low
      level of GM-CSF activity was constitutively present in all astrocytomas. G-CSF
      was detected in unstimulated U87MG and U138MG and other cell lines could
      synthesize G-CSF after the stimulation of IL-1 beta and TNF-alpha at the level of
      mRNA. Furthermore, the concentration of CSFs increased markedly upon stimulation
      with IL-1 beta and/or TNF-alpha in both a time- and dose-dependent fashion. From
      these results, it is suspected that astroglial cell-derived CSFs may participate
      in local immune reactions accompanying infection, degeneration and malignancies
      in the brain.

PMID- 1377085
TI  - Glutamic acid-insensitive [3H]kainic acid binding in goldfish brain.
AB  - Kainic acid is supposed to be a specific agonist for a subclass of excitatory
      glutamate receptors in the vertebrate CNS. An investigation of (2 nM) [3H]kainic
      acid binding sites in goldfish brain, using quantitative autoradiography, has
      revealed evidence for two types of kainic acid receptors which differ in
      sensitivity to glutamic acid. L-Glutamic acid (0.1-1 mM) displaced over 95% of
      specific [3H]kainic acid binding elsewhere in the brain but only 10-50% in the
      cerebellum and cerebellar crest. These structures apparently contain [3H]kainic
      acid binding sites that are extremely insensitive to glutamic acid. The glutamic
      acid-insensitive [3H]kainic acid binding was not displaced by quisqualic acid,
      kynurenic acid, alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA), or
      N-methyl-D-aspartatic acid, but was completely displaced by the kainic acid
      analogue domoic acid. The data indicate that two types of high affinity binding
      sites for [3H]kainic acid exist in the goldfish brain: glutamic acid-sensitive
      and glutamic acid-insensitive. High affinity [3H]kainic acid binding may
      therefore not always represent binding to subsets of glutamic acid receptors.

PMID- 1377086
TI  - Mechanisms of action of ibogaine and harmaline congeners based on radioligand
      binding studies.
AB  - Assays using radioligands were used to assess the actions of ibogaine and
      harmaline on various receptor types. Ibogaine congeners showed affinity for
      opiate receptors whereas harmaline and harmine did not. The Ki for coronaridine
      was 2.0 microM at mu-opiate receptors. The Kis for coronaridine and tabernanthine
      at the delta-opiate receptors were 8.1 and 3.1 microM, respectively. Ibogaine,
      ibogamine, coronaridine and tabernanthine had Ki values of 2.08, 2.6, 4.3 and
      0.15 microM, respectively, for kappa-opiate receptors. Long-lasting, dose
      dependent behavioral effects of ibogaine have been reported. The possibility that
      these effects were due to irreversible binding properties of ibogaine at kappa
      receptors was considered; however, radioligand wash experiments showed a rapid
      recovery of radioligand binding after one wash. A voltage-dependent sodium
      channel radioligand demonstrated Ki values in the microM range for all drugs
      tested. Using radioligand binding assays and/or 36Cl- uptake studies, no
      interaction of ibogaine or harmaline with the GABA receptor-ionophore was found.
      The kappa-activity of ibogaine (or an active metabolite) may be responsible for
      its putative anti-addictive properties whereas the tremorigenic properties of
      ibogaine and harmaline may be due to their effects on sodium channels.

PMID- 1377087
TI  - Recovery from lateralized neocortical damage: dissociation between amphetamine
      induced asymmetry in behavior and striatal dopamine neurotransmission in vivo.
AB  - It has been hypothesized that neocortical damage is accompanied by secondary
      changes in other brain areas (the shock or diaschisis of von Monakow), which
      contributes to initial non-specific behavioral depression. The relation between
      behavioral changes and dopamine (DA), serotonin (5-HT), and their metabolites,
      measured with intracerebral microdialysis in freely moving rats and by tissue
      assay postmortem, was examined during postsurgical recovery from unilateral
      hemidecortications. Rats were tested for rotational asymmetry and extracellular
      concentration of DA was measured both during rest and after amphetamine (1.5
      mg/kg). It was found that: (1) during the first few postsurgical days the
      hemidecorticate rats rotated ipsilateral to their lesions after amphetamine but
      thereafter on tests given up to 121 days postsurgery concentration of DA or its
      metabolites at any time after surgery; (3) the 5-HT metabolite 5
      hydroxyindoleacetic acid (5-HIAA) was elevated acutely for a few days following
      surgery; (4) during the first 3 postoperative days, both baseline extracellular
      3,4-dihydroxyphenylacetic acid (DOPAC) and amphetamine-induced DA release were
      significantly elevated bilaterally. These findings demonstrate that the acute
      behavioral asymmetry in rotation produced by hemidecortication is not related to
      unilateral changes in striatal DA activity and its metabolites. Thus, the
      behavioral asymmetries might be related to other striatal changes (i.e. 5-HIAA)
      or other damage, such as to the corticospinal projections of the lesioned
      hemisphere. Nevertheless, unilateral lesions did produce acute bilateral
      increases in DA levels, which may be a correlate of generalized neural shock
      produced by the lesion.

PMID- 1377088
TI  - In vivo microdialysis reveals a diminished amphetamine-induced DA response
      corresponding to behavioral sensitization produced by repeated amphetamine
      pretreatment.
AB  - In vivo microdialysis procedures were used to assess the effects of repeated
      amphetamine administration on behavior and regional brain DA dynamics in freely
      moving rats. Pretreatment with amphetamine (2.5 or 3.0 mg/kg) for 4-6 days did
      not alter baseline DA or its metabolites in caudate or accumbens 48 h or 6 days
      after the last injection. However, whereas this dosage regimen revealed a
      profound behavioral sensitization in response to challenge with amphetamine (2.5
      mg/kg), including a more rapid onset and intensification of stereotypy, the DA
      response was significantly diminished in both brain regions. In addition, the
      ratio of caudate to accumbens DA, either before or after amphetamine challenge,
      was not altered by the pretreatment regimen. These results are consistent with
      our previous suggestion that there is a dissociation between the DA and
      behavioral responses to amphetamine, and therefore that other neurotransmitter
      systems and/or mechanisms significantly contribute to the amphetamine response
      profile. Furthermore, DA effects may represent only one, albeit critical, aspect
      in a time-dependent sequence of changes underlying stimulant sensitization.

PMID- 1377089
TI  - Ethanol inhibition of N-methyl-D-aspartate-activated ion current in rat
      hippocampal neurons is not competitive with glycine.
AB  - The interaction of ethanol with glycine at the N-methyl-D-aspartate (NMDA)
      activated ion channel was investigated in voltage-clamped rat cultured
      hippocampal neurons. As shown previously, glycine increased, and ethanol
      inhibited, the NMDA-activated current in these cells. Concentration-response data
      for glycine (0.1-100 microM) indicate that the inhibition of NMDA-activated
      current by ethanol does not involve a competitive interaction with glycine. Thus,
      ethanol appears to inhibit NMDA-activated current at a locus different from the
      glycine modulatory site.

PMID- 1377090
TI  - Ultrastructural double-labeling demonstrates synaptic contacts between
      dopaminergic terminals and substance P-containing striatal neurons in pigeons.
AB  - Immunohistochemical studies in rats have demonstrated dopaminergic input onto
      medium spiny neurons of the striatum. Medium spiny neurons, however, are known to
      consist of two major neuropeptide-specific types, those containing substance P
      (SP) and those containing enkephalin. Although both of these types have been
      shown to receive dopaminergic input onto their perikarya and proximal dendrites,
      the extent to which both types also receive direct dopaminergic input onto distal
      dendritic shafts or onto dendritic spines is uncertain. In the present study, we
      used EM immunohistochemical double-label techniques to examine the synaptic
      organization of dopaminergic input onto SP+ striatal neurons. We examined the
      striatum of pigeons, in whom SP+ striatal neurons, including their dendritic
      shafts and spines, can be readily labeled. Antibodies against tyrosine
      hydroxylase (TH) were used to identify dopaminergic terminals, which were labeled
      using silver-intensified immunogold. The SP+ neurons were labeled
      immunohistochemically using diaminobenzidine. We found that dopaminergic
      terminals make appositions and form symmetric synapses with the perikarya,
      dendritic shafts and dendritic spines of SP+ neurons. Thus, nigral dopaminergic
      neurons provide a monosynaptic input onto SP+ striatal neurons in a manner
      similar to that described for dopaminergic input onto striatal medium spiny
      neurons in general.

PMID- 1377091
TI  - Inhibition of proliferative responses of lymphocytes to food antigens by an anti
      allergic drug, N(3',4'-dimethoxycinnamoyl) anthranilic acid (Tranilast) in
      children with atopic dermatitis.
AB  - Experimental studies have shown that N(3',4'-dimethoxycinnamoyl) anthranilic acid
      (Tranilast) inhibits reaginic antibody-mediated hypersensitivity reactions, and
      it has been demonstrated to be an effective drug for patients with bronchial
      asthma. On the other hand, from the nature of the cellular infiltrate seen in
      eczematous lesions, it appears that some form of cell-mediated immunity may be
      involved in addition to IgE-mediated immunity in the pathogenesis of atopic
      dermatitis (AD). Moreover, we have previously reported that the proliferative
      responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) or
      bovine serum albumin (BSA) in children with AD who are sensitive to hen's egg or
      cow's milk were significantly higher than those of healthy children and hen's egg
      or cow's milk sensitive children with immediate symptoms. In this study, we have
      showed that the proliferative responses of PBMCs to OA were dose-dependently
      inhibited by Tranilast on patients with AD. The responding cells to OA were
      shown, through separation experiments, to be T cells, and the proliferative
      responses of T cells to OA were also dose-dependently inhibited by Tranilast.
      Moreover, the inhibition was thought to occur at the initial stage of the
      proliferative reactions. These results suggest that Tranilast can be clinically
      applied to patients with AD.

PMID- 1377092
TI  - Crossreacting IgE antibodies to Pityrosporum ovale and Candida albicans in atopic
      children.
AB  - Sera from 13 patients with positive Pityrosporum ovale skin prick test were
      analysed with IgE immunoblotting. Both P. ovale and Candida albicans antigens
      were used to reveal possible crossreactivity of these yeasts. Of the 13 sera,
      eight sera showed IgE binding to P. ovale and six sera to C. albicans.
      Simultaneous IgE-binding to both C. albicans and P. ovale was observed in five of
      these sera. The most common IgE-binding band pairs were, a 23 kD band of P. ovale
      and a 27 kD band of C. albicans, as one pair, and a 26 kD band and a 13 kD band,
      respectively, as another pair. In addition to these protein bands, simultaneous
      reactivity was observed to C. albicans mannan, a polysaccharide, and to a diffuse
      high molecular weight component of P. ovale, possibly also a polysaccharide. The
      five sera with simultaneous IgE-binding were analysed with RAST-inhibition, which
      revealed presence of crossreacting IgE-antibodies to P. ovale and C. albicans in
      two of these sera. Crossreacting epitopes were suggested to be located in the
      mannan polysaccharide of C. albicans and high molecular weight diffuse stain of
      P. ovale, based on the immunoblotting and RAST-inhibition patterns of the studied
      sera. Crossreacting sera were pooled and used as an IgE probe in CRIE and Tandem
      CRIE. These experiments revealed a fused precipitin line indicating presence of a
      common structure of P. ovale and C. albicans. This suggested crossreactivity may
      imply an interesting phenomenon in atopics who are sensitized by C. albicans
      growth in the gastrointestinal tract and get exposed by P. ovale growing on the
      skin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377093
TI  - Characterization of a monoclonal antibody (P40) against the 68 kD major allergen
      of Penicillium notatum.
AB  - A monoclonal antibody (MoAb P40) against the 68 kD major allergen of Penicillium
      notatum (P. notatum) was obtained by immunizing the mouse with a crude extract of
      P. notatum. Analysed by two-dimensional gel electrophoresis and immunoblotting,
      P40 reacted with two different isoforms of the 68 kD component of P. notatum with
      pIs of 5.4 and 5.5. In addition to P. notatum, P40 showed positive ELISA activity
      to Aspergillus fumigatus (A. fumigatus) but not to components of six other fungi
      including Alternaria porri, Cladosporium cladosporoides, Aureobasidium pullulans,
      Fusarium solani, Rhizopus arrhizus and Candida albicans. Analysed by ELISA, MoAb
      P40 also showed positive activity to two (P. frequentans and P. roseopurpureum)
      of the 10 other Penicillium species and two (A. terreus and A. flavus) of the
      four other Aspergillus species tested. SDS-PAGE and immunoblotting studies
      demonstrated P40 positive reactivity to components with MW of about 67 kD in all
      these Penicillium and Aspergillus species with positive ELISA activity to P40.
      Furthermore, immunoblotting activity of MoAb P40 to the 67 kD component of A.
      niger was also observed. The epitope of the 68 kD allergen of P. notatum
      recognized by MoAb P40 was resistant to treatment of periodate oxidation with
      concentration of NaIO4 up to 20 mM. This MoAb may thus be useful in the
      characterization and purification of the 68 kD allergen from crude extracts, and
      in the molecular cloning of allergen genes.

PMID- 1377094
TI  - Transposon Tn5-259 mutagenesis of Pseudomonas cepacia to isolate mutants
      deficient in antifungal activity.
AB  - Transposon Tn5-259 was inserted into the chromosome of Pseudomonas cepacia by
      mating with an Escherichia coli strain harboring a self-mobilizable, temperature
      sensitive plasmid, pME12. Data from Southern blots and auxotroph analyses
      indicated that a single copy of the transposon was inserted in several places
      into the chromosome of P. cepacia. Among 1500 Tn5-259 transconjugants, only one
      mutant was found to be defective in the production of an antifungal compound,
      pyrrolnitrin. In addition, this mutant lost its ability to antagonize fungal
      phytopathogens. Using flanking DNA of the mutated gene as a probe, we have
      isolated four overlapping cosmid clones from a genomic library of P. cepacia.
      However, we were unable to complement the mutant because of difficulty in
      mobilizing the cosmids from E. coli to P. cepacia.

PMID- 1377095
TI  - Child psychiatry and early intervention: III. The developmental disorders.
AB  - This paper is the third in a series of four using the concepts introduced in the
      paper Child Psychiatry and Early Intervention: I. The Aggregate Burden of
      Suffering. This paper reviews the developmental disorders of childhood to set
      priorities for early intervention programs. This review discusses the prevalence,
      course, risk, early indicators, associated impairments, and responses to
      intervention. The specific developmental disorders, especially learning
      disabilities, have a significant impact on community resources. Since the
      developmental disorders are easily recognized among preschool children, early
      intervention is feasible. However, successful interventions have yet to be
      demonstrated. Priority should be given to the development of effective
      interventions. There is a great need for research studies on the effects and
      effectiveness of early intervention with these individuals.

PMID- 1377096
TI  - Amiloride but not bumetanide protects against the cytotoxic effects of
      estramustine and bleomycin in cultured fibroblasts.
AB  - The effects of the clinically used diuretics amiloride (an inhibitor of Na+/H+
      exchange) and bumetanide (an inhibitor of Na+, K+, Cl- co-transport) were tested
      on the cytotoxicity of estramustine and bleomycin in cultured fibroblasts. Both
      estramustine (50 micrograms/ml) and bleomycin (10 micrograms/ml) reduced the
      number of surviving clones. Amiloride (100 microM) but not bumetanide (100
      microM) partly protected against the cytotoxic effect of both estramustine and
      bleomycin. The protective effect of the combination of amiloride and bumetanide
      was not stronger than the effect of amiloride alone. Amiloride or bumetanide
      alone did not affect the clonal survival. It is suggested that the protective
      effect of amiloride is not mediated by an effect of the molecular mechanism of
      cytotoxicity but may rather be due to changes in cellular metabolism and/or drug
      handling.

PMID- 1377097
TI  - Treatment of the carcinoid syndrome with somatostatin, salmon calcitonin, or
      octreotide.
AB  - Three patients with the carcinoid syndrome received intravenous somatostatin (3.5
      micrograms/min) for one day; intravenous salmon calcitonin (8 IU/hr) for one day;
      subcutaneous salmon calcitonin (100 IU three times daily) for ten days; and
      subcutaneous octreotide (150 micrograms three times daily) for ten days.
      Octreotide (SMS-201.995) is a stable analogue of somatostatin. There was a five
      day washout period between each treatment. During each of these treatments,
      reductions in the numbers of daily flushes and bowel movements, stool weight, and
      urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were observed. Relief of
      cramping abdominal pains was also reported. Patients 1 and 3 chose to continue
      receiving the subcutaneous calcitonin and patient 2 chose the octreotide. Patient
      1 (aged 67 years) reported relief of symptoms for five months until she developed
      an intestinal obstruction as a result of tumor infiltration. Patient 3 (aged 67
      years) has received the calcitonin for about 16 months with relief of symptoms
      and reduced urinary 5-HIAA levels. Patient 2 (aged 57 years) has continued
      octreotide treatment for one year and reports relief of symptoms.

PMID- 1377098
TI  - A nuclear mutation affects the synthesis of the chloroplast psbA gene production
      Chlamydomonas reinhardtii.
AB  - The effect of the nuclear mutation F34 on the synthesis of chloroplast-encoded
      photosystem II (PSII) polypeptides has been controversial. While we had concluded
      that the synthesis of the psbC gene product (P6) was specifically deficient in
      this mutant, another laboratory has found that the synthesis of the psbA gene
      product, the herbicide-binding protein D1, was primarily affected. These
      conflicting results were re-analyzed through genetic and biochemical
      characterization of the different strains used by the two laboratories in
      question. While the strain used in our laboratory carries the single F34 mutation
      responsible for the deficiency of P6, the other strain contains three nuclear
      mutations: the original F34 mutation, a suppressor mutation of F34 and a second
      PSII mutation, F35. Mutation F35 does not affect P6 synthesis but is responsible
      for the deficiency in the synthesis of the herbicide-binding protein D1.
      Furthermore, since both F34 and F35 mutant strains accumulate wild-type levels of
      psbC and psbA transcripts, we show that these nuclear mutations affect nuclear
      genes whose products are involved in the expression of psbC or psbA at a post
      transcriptional level.

PMID- 1377100
TI  - Chemical modification of fumagillin. II. 6-Amino-6-deoxyfumagillol and its
      derivatives.
AB  - 6-Amino-6-deoxyfumagillol (5) was synthesized by reductive amination of 6-oxo-6
      deoxyfumagillol (4), which was obtained by oxidation of fumagillol (2). The
      reduction proceeded stereoselectively by the equatorial attack of hydride and 5
      was found to have the same stereochemistry as that of 2. Several derivatives of 5
      were prepared and most of them showed anti-angiogenic activity comparable to that
      of fumagillol derivatives.

PMID- 1377099
TI  - The higher plant nad5 mitochondrial gene: a conserved discontinuous transcription
      pattern.
AB  - The single copy nad5 gene has been identified in the mitochondrial genomes of
      cauliflower, chicory, potato, fennel, and common bean. In these five dicot
      species the same organization as in Oenothera, Arabidopsis, wheat, and maize has
      been found for the gene: it consists of five exons organized into three
      independent groups. The first group comprises exons I and II, separated by a
      highly conserved group II intron, while the second group consists of exon III
      only. In the third group exons IV and V are separated by a group II intron of
      variable, species-specific, length. Transcription analysis of the nad5 gene in
      chicory and in cauliflower shows that the five exons are assembled as a mature
      mRNA through intermolecular interactions and multiple splicing events. Comparison
      of transcription in the gene with that of wheat and maize suggests that a common
      mechanism exists in higher plants for nad5 transcript processing.

PMID- 1377101
TI  - Suppressive effect of polyoxometalates on the cytopathogenicity of human
      immunodeficiency virus type 1 (HIV-1) in vitro and their inhibitory activity
      against HIV-1 reverse transcriptase.
AB  - One isopolyoxometalate and 42 heteropolyoxometalates consisting of 3 compounds
      with the trivacant Keggin structure, 2 with the lacunary Keggin structure, 30
      with the Keggin structure, one with the Wells-Dawson structure and 6 with
      miscellaneous structures were tested for their suppressive effect on the
      cytopathogenicity of human immunodeficiency virus type 1 (HIV-1) in vitro and
      inhibitory activity against HIV-1 reverse transcriptase. In contrast to the
      leading interpretations which attribute the suppressive effect of
      polyoxometalates on the cytopathogenicity of HIV-1 to the inhibition of HIV-1
      reverse transcriptase by these compounds, there was no distinct correlation
      observed between these two functions of polyoxometalates.

PMID- 1377103
TI  - Reduction of endotoxin-induced vascular permeability by monoclonal antibodies
      against lipopolysaccharide determinants.
AB  - Endotoxin, a bacterial lipopolysaccharide implicated in the pathogenesis of
      septic shock, markedly alters vascular permeability following intravenous
      injection in rabbits. We investigated the ability of murine monoclonal antibodies
      to confer protection against endotoxin-induced increases in a rabbit model of
      ocular vascular permeability. Four monoclonal antibodies of differing
      specificities as well as polymyxin B were compared for their effects on endotoxin
      from either Escherichia coli or Pseudomonas aeruginosa. Preincubation of
      endotoxin with antibodies directed against Pseudomonas O side chain or core
      glycolipid resulted in marked attenuation of vascular permeability due to
      Pseudomonas endotoxin, but not E. coli endotoxin. Antilipid A antibodies were not
      significantly effective in neutralizing either endotoxin with in vitro
      preincubation. Low avidity of the antilipid A antibody, low density of lipid A
      binding sites, or inaccessibility of the lipid A may have prevented more marked
      interactions. When administered intravenously prior to endotoxin challenge, none
      of the antibodies demonstrated the ability to provide specific protection to
      subsequent endotoxin in this model. They did provide partial nonspecific
      protection against endotoxins regardless of epitope specificity. When
      administered prophylactically, polymyxin B, an antibiotic that binds to lipid A,
      was highly effective in neutralizing the toxic effects of endotoxin. Since
      antibodies to lipid A reduce mortality in septic shock, the failure to
      demonstrate efficacy in this study may be due to the marked sensitivity of the
      rabbit eye to endotoxin. Alternatively, beneficial effects from antiendotoxin
      antibodies in septic shock may be unrelated to the inhibition of vascular
      permeability. Some protection from antiendotoxin antibodies may be due to
      enhancement of nonspecific mechanisms.

PMID- 1377102
TI  - Synergistic antiproliferative effect of interferons and azidothymidine on HL60
      cells.
AB  - Proliferation of human leukemia cells, HL60, was synergistically inhibited by a
      combination of human interferons and azidothymidine in vitro. Combination of
      interferon-gamma (3000 U/ml) and azidothymidine (30 microM) inhibited cell growth
      by 76%, whereas interferon-gamma alone suppressed growth by 23% and
      azidothymidine alone by 33%. Interferon-alpha-2a and interferon-beta also exerted
      synergistic effects with azidothymidine, but the potentiation was weaker than
      that by the combination of interferon-gamma and aziodthymidine.

PMID- 1377104
TI  - Development of aging-associated monoclonal gammapathies with antibody activity to
      the antigen used for immunization of young mice.
AB  - The influence of immunization with dinitrophenylated human serum albumin (DNP
      HSA) at a young age on the development of age-related monoclonal gammapathies
      (MG) was investigated in a longitudinal study in intact and neonatally
      thymectomized (NTx) C57BL/KaLwRij and CBA/BrARij mice. Three-month-old mice were
      immunized four times in monthly intervals with DNP-HSA. Control mice received
      saline and adjuvant only. Mice immunized with DNP-HSA responded with
      heterogeneous antibodies, occasionally with some clonal dominance. The antibody
      levels further declined and were hardly detectable when the mice were 21 months
      old. Eighteen of 87 experimental mice developed homogeneous antibody components
      (H-Ab) to DNP-HSA with aging. Their frequencies per individual groups were 5, 22,
      24, and 29% for intact CBA, NTx-CBA, NTx-C57BL, and intact C57BL mice,
      respectively. Some H-Ab had the same mobility and similar spectrotypes as
      dominant clonal products at the peak of the response. However, the majority of H
      Ab appearing at old age were "new" H-Ab. While most of H-Ab in the CBA mice were
      transient and of a low concentration, the majority of H-Ab in the C57BL mice had
      all characteristics of a benign monoclonal gammapathy. The results indicate that
      memory cells of the B cell clones involved in the original specific response may
      in a susceptible strain become targets for events leading to the development of
      benign monoclonal gammapathy.

PMID- 1377105
TI  - Shift of private and not of cross-reactive anti-DNA idiotypes in systemic lupus
      erythematosus.
AB  - The shift of private idiotype (Id) and cross-reactive Id (CRI) on anti-DNA
      antibodies in a lupus patient KE was investigated during a 7-year period. Anti
      private Id and anti-CRI activities were separated by affinity chromatography from
      rabbit (R)-anti-Ids raised against KE anti-DNA antibodies during active (1/84)
      and inactive (4/90) stages of the disease. Anti-CRI isolated from the 84 R-anti
      Id appeared to recognize binding site-related Ids that are shared with KE non
      anti-DNA antibodies, unrelated lupus patients' sera, and certain normal sera. Id
      expression on serial serum samples of KE using these fractionated R-anti-Ids as
      probes showed that the 1/84 private Id expression declined while the 4/90 private
      Id expression gradually increased. Expression of the CRI showed a relatively
      stable pattern. These results suggest that anti-DNA populations detected by anti
      private Id can shift, while populations expressing CRI may stay stable.

PMID- 1377106
TI  - [A case of acute idiopathic pandysautonomia--a histochemical study of sural nerve
      by acetylcholinesterase staining].
AB  - A 30-year-old man had an acute onset of orthostatic lightheadedness, sweating
      disturbance, paroxysmal cough and loss of potency. These symptoms reached the
      peak in two weeks, and then remitted very slowly. He was admitted to our hospital
      for further evaluation when he was 39 years old. Neurological examinations
      revealed right Horner's syndrome, dry skin and impotence, but neither motor nor
      sensory system was impaired. No abnormalities were found on routine examinations
      of the blood and cerebrospinal fluid, motor and sensory nerve velocities,
      computed tomography and electroencephalography. On sural nerve biopsy, the
      density of unmyelinated fibers was mildly decreased (13,857/mm2), whereas that of
      myelinated fibers was normal (7,220/mm2). Autonomic function tests disclosed
      orthostatic hypotension (-31 mmHg) on tilting, reduced levels of serum
      noradrenaline and vanillyl mandelic acid, supersensitive responses to
      noradrenaline infusion and adrenaline eye-dripping, severe sweating impairment
      and complete absence of sympathetic skin response. On the other hand, Aschner's
      test, Czermak's test and coefficient variation of R-R intervals were all normal.
      These results suggested that the chief lesion was located in the postganglionic
      fiber of sympathetic efferent pathway. We (Hayashi et al, 1990) quantified
      acetylcholinesterase (AchE)-positive fibers in the specimens of sural nerve
      biopsy, and reported that the density of AchE-positive fibers was correlated to
      the function of sympathetic postganglionic fibers. The density of AchE-positive
      fibers in the present case of acute idiopathic pandysautonomia (AIPD) was
      severely decreased to 225/mm2 by optical microscopy (control: 5,703 +/-
      1,289/mm2), and to 2,996/mm2 by electron microscopy (control: 14,112 +/-
      3,987/mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377107
TI  - Biochemical parameters as a measure of food availability and growth in immature
      rainbow trout (Oncorhynchus mykiss).
AB  - 1. Rainbow trout held in brackish water (15 parts per thousand) were starved or
      fed different amounts of food. 2. A significant correlation was found between the
      growth rates of the different animals and the feed rates. 3. The RNA:DNA ratio in
      the white epaxial muscle is lowest in starved fish and increases in proportion to
      the feed rate and individual specific growth rate. The correlations are
      significant at the P less than 0.01 level. 4. Liver metabolism varies according
      to food availability. 5. The protein synthesis capacity of the liver (RNA:DNA
      ratio) and liver somatic index increase as the feeding rate increases. It also
      correlates significantly with the specific growth rates of the different animals.
      6. The intermediary metabolism of the central metabolic organ, the liver, varies
      in the same way. 7. The activities of the NADPH producing liver enzymes glucose-6
      phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH),
      isocitrate dehydrogenase (IDH) and malic enzyme (ME) increase as the feed rate
      (and therefore the specific growth rate) increases. 8. G6PDH and IDH activity in
      the kidney is influenced to a much lower degree by food intake. 9. Summarizing,
      it can be stated that biochemical parameters can be used to describe
      comprehensively the metabolic status and growth of rainbow trout.

PMID- 1377108
TI  - Adaptive significance of amylase polymorphism in Drosophila--VI. Properties of
      two amylase variants and the effect of food components on amylase activity in
      Drosophila subobscura.
AB  - 1. Properties of amylase from two D. subobscura strains homozygous for two
      different amylase variants (AmyS and AmyF) were determined. 2. Amylase of both
      strain adults showed a pH optimum of 7.8. 3. The AmyF enzyme showed a higher
      thermostability. 4. They differed in both maximum activity and Michaelis constant
      (Vmax of 6.25 and 3.45, Km of 0.7% and 0.42% starch for AmyS and AmyF,
      respectively). 5. The effect of different feeding conditions in amylase activity
      in the above Drosophila strains was also studied. Amylase activity was always
      detected but to a different level depending on diet composition.

PMID- 1377109
TI  - The c-src tyrosine kinase (CSK) gene, a potential antioncogene, localizes to
      human chromosome region 15q23----q25.
AB  - We have previously reported the cloning of a novel cytoplasmic tyrosine kinase,
      CSK. This tyrosine kinase has been shown to downregulate the tyrosine kinase
      activity of the c-src oncoprotein through tyrosine phosphorylation of the c-src
      carboxyl terminus. Cell transformation by src oncoproteins is caused by several
      oncogenic mechanisms, which interfere with this phosphorylation. The CSK gene
      could therefore potentially function as an antioncogene. We have here mapped the
      CSK gene to 15q23----q25 by in situ hybridization.

PMID- 1377110
TI  - Fat and pancreatic secretion. Studies on the humoral regulation in man.

PMID- 1377111
TI  - Drug therapy in the 1990s. What can we expect for cystic fibrosis?

PMID- 1377112
TI  - Cyclosporin for Crohn's disease?

PMID- 1377113
TI  - Pharmacological agents affecting emesis. A review (Part II).
AB  - Part I of this article reviewed the pathophysiology of emesis, and its
      pharmacological treatment. Drug-induced vomiting was also discussed. In the
      second part of the review, other common causes of vomiting are considered. The
      basis of the use of antiemetics in morning sickness and migraine is still
      obscure; for the latter, serotonin 5-HT1 receptor agonists, 5-HT3 receptor
      antagonists and dopamine D2 receptor antagonists are effective. For motion
      sickness, control can be achieved with various antagonists of muscarinic or
      histamine H1-receptors. Centrally active adrenoceptor agonists in combination
      with a muscarinic antagonist or H1-receptor antagonist may offer better control
      of motion sickness and its associated symptoms than either antagonist alone;
      based on clinical studies, postoperative vomiting after opiate administration
      appears to be controlled by blocking dopamine D2, histamine H1- or muscarinic
      receptors. Radiation therapy appears to be similar to cytotoxic therapy in that
      the mediators produced or released by radiation activate both peripheral and
      central sites involved in the vomiting reflex. Blockade of dopamine D2 and 5-HT3
      receptors may be effective.

PMID- 1377114
TI  - Recent advances in pharmacological management of hypertension in diabetic
      patients with nephropathy. Effects of antihypertensive drugs on kidney function
      and insulin sensitivity.
AB  - Hypertension is often seen in Type 1 and Type 2 diabetic patients, particularly
      in those with nephropathy, and the progression of diabetic nephropathy is closely
      related to blood pressure elevation. Thus, the effects of antihypertensive drugs
      on kidney function and insulin sensitivity in diabetic patients are of great
      clinical importance. Successful antihypertensive treatment has been shown to slow
      the progression of diabetic nephropathy. Several results from short term studies
      have suggested that angiotensin converting enzyme (ACE) inhibitors may be
      advantageous over other conventional antihypertensive agents in reducing
      albuminuria in both hypertensive and normotensive diabetics with microalbuminuria
      or persistent proteinuria. However, the decline in glomerular filtration rate
      during ACE inhibitor treatment is comparable to that during effective treatment
      with conventional antihypertensive drugs in hypertensive Type 1 diabetic patients
      with overt nephropathy. Whether ACE inhibitors possess a specific effect in
      preventing the development of diabetic nephropathy remains to be seen in properly
      designed long term studies. Although calcium antagonists may preserve kidney
      function or possess a renoprotective effect in hypertensive Type 2 diabetics with
      nephropathy, firm evidence supporting this contention seems to be lacking and
      also requires long term evaluation. Increasing attention is being directed toward
      the effect of antihypertensive drugs on insulin sensitivity in diabetic patients:
      ACE inhibitors and alpha 1-adrenoceptor blocking agents have been shown to
      improve this sensitivity. Despite the widespread involvement of calcium in
      hormone secretion and action, calcium antagonists appear to have little effects
      on the glucoregulatory and calcium-regulatory hormones within the drug dosages
      used in clinical practice. Several clinical variables, such as the presence or
      absence of hypertension, overt nephropathy and microalbuminuria, or a combination
      of variables should be accounted for when evaluating critically the cumulative
      data on the effects of antihypertensive drugs on kidney function and albuminuria
      in the variety of diabetic patient groups. Understanding the pharmacokinetic and
      pharmacodynamic characteristics of antihypertensive drugs will be of clinical
      importance in diabetic patients with advanced nephropathy (glomerular filtration
      rate of less than 30 ml/min) and/or other complications, such as impaired gastric
      motility or gastroparesis, and will thereby lead to a more rational management of
      hypertension in those patients.

PMID- 1377115
TI  - Guidelines for the treatment of vitiligo.
AB  - At present, there is no universally effective drug for vitiligo therapy; there
      are, however, various therapeutic modalities that may be beneficial. Therapeutic
      regimens used to treat vitiligo include psoralens and ultraviolet A light (PUVA),
      topical corticosteroids, fluorouracil locally applied with skin abrasion, a
      variety of surgical techniques to transplant autologous melanocytes from
      pigmented skin to nonpigmenting areas, a new photochemotherapeutic regimen using
      oral khellin with UVA phototherapy, and a recently proposed treatment with oral
      phenylalanine in combination with UVA exposure. PUVA and topical corticosteroids
      are the 2 most frequently used modalities. The use of effective sunscreens with a
      high sun protection factor (SPF) is of help in preventing the vitiliginous areas
      from burning and normal skin from becoming tanned. Cosmetic camouflage is also
      useful to disguise the white areas of skin. Finally, depigmentation should be
      considered in patients with greater than 50% cutaneous involvement who fail to
      respond or are unwilling to undergo treatment. The selection of patients for
      therapy should take into consideration the patient's motivation, the
      psychological impact of the disease and the clinical presentation of vitiligo,
      and should weigh the risks and benefits of prolonged therapy.

PMID- 1377116
TI  - Cancer-associated anorexia and cachexia. Implications for drug therapy.
AB  - Anorexia and cachexia are major problems in patients with cancer. Such measures
      as anti-cancer therapy, dietary counselling or hyperalimentation are not very
      successful in reversing this phenomenon in the vast majority of cancer patients.
      Thus, several drugs have been evaluated as agents to ameliorate cancer-associated
      anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to
      cause slight appetite stimulation in patients. A randomised clinical trial,
      however, was unable to demonstrate any weight gain from this agent.
      Corticosteroids are frequently used in clinical practice for appetite stimulation
      in patients with advanced malignancies. Supporting this practice, 4 randomised
      clinical trials showed that corticosteroid medications can stimulate the
      appetites of advanced cancer patients. However, these studies were not able to
      show any substantial nonfluid weight gain in treated patients. Megestrol acetate
      is a progestational agent which appears to be a relatively potent appetite
      stimulant. Randomised studies in advanced cancer patients have shown both
      substantial appetite stimulation and improvement in the nonfluid bodyweights of
      patients receiving this drug. Preliminary evidence also suggests that this drug
      has antiemetic properties. Several clinical studies are currently ongoing to
      determine the effect of various doses of megestrol acetate in patients with
      cancer. Efforts are also ongoing to evaluate both anabolic steroids and hydrazine
      sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The
      preliminary nature of these investigations, however, precludes recommendations
      for the use of either of these latter 2 drugs in routine clinical practice.

PMID- 1377118
TI  - Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). A review
      of its pharmacological properties and prospective role in the management of
      myelosuppression.
AB  - Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a
      polypeptide hormone produced through recombinant DNA technologies in glycosylated
      (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli
      expression system) form. It is a multilineage haematopoietin which stimulates
      proliferation and differentiation of bone marrow myeloid progenitors and
      increases peripheral white blood cell counts when administered systemically.
      Treatment is generally well tolerated, although mild to moderate flu-like
      symptoms are common and rGM-CSF-induced fever and fluid retention may be
      problematic in occasional patients. rGM-CSF accelerates recovery of peripheral
      neutrophil counts after bone marrow transplantation, and results of a placebo
      controlled randomised trial correlate this with reduced infectious episodes and
      shortened length of hospitalisation in patients with lymphoid malignancies. A
      substantial number of patients with graft failure after bone marrow
      transplantation also respond to rGM-CSF. The duration of myelosuppression
      secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which
      has permitted investigation of antineoplastic dose-intensity escalation. In some
      haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia
      secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically
      useful increases in peripheral blood granulocyte counts, although the effect is
      generally not sustained after drug withdrawal. The potential for rGM-CSF to
      stimulate proliferation of the abnormal clone in myelodysplasia and in acute
      myelogenous leukaemia following induction therapy is of concern. Available data
      suggest, however, that with appropriate monitoring and exclusion of high-risk
      patients this serious potential risk can be avoided, and that myelopoiesis is
      enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating
      factors are a new therapeutic modality; hence many aspects of their use remain to
      be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has
      major potential in the management of myelosuppression secondary to cytoreductive
      therapy with or without bone marrow transplantation, and in amelioration of
      disturbed myelopoiesis. It represents an important application of biotechnology
      to a difficult area of therapeutics.

PMID- 1377117
TI  - The use of sedative agents in critically ill patients.
AB  - The main aim of sedation in the critically ill patient is to provide relief from
      anxiety and pain. The current, ideal level of sedation should leave a patient who
      is lightly asleep but easily roused. No single regimen is suitable for all
      patients. The level of sedation should be monitored, and the choice of agent, the
      dose and the route of administration adjusted appropriately. Midazolam is often
      used to provide sleep and anxiolysis. Alternatives include propofol and
      isoflurane. Propofol is easily titrated to achieve the desired level of sedation,
      and its effects rapidly end when the infusion is stopped. Isoflurane also appears
      promising, but special equipment is needed for its administration. Morphine is
      the standard analgesic agent. The principal metabolites, morphine-6-glucuronide,
      is also a potent opioid agonist and may accumulate in renal failure. Of the newer
      analgesic agents, alfentanil is an ideal agent for infusion, and may be the agent
      of choice in renal failure. Neuromuscular blocking agents are indicated only in
      specific circumstances, and used only once it is known patients are asleep and
      pain free. The actions of these agents are unpredictable in the critically ill
      patient. Alterations in drug effect and elimination may occur, especially in the
      patient with hepatic and renal failure. This may also apply to active metabolites
      of the parent drug. When planning sedation regimens, specific patient needs and
      staffing levels must be remembered. Attention to the environment is also
      important. Midazolam and morphine given by intermittent bolus or by infusion are
      the mainstay of most regimens. Propofol is ideal for short periods of care on the
      ICU, and during weaning when longer acting agents are being eliminated.

PMID- 1377119
TI  - Moclobemide. A review of its pharmacological properties and therapeutic use in
      depressive illness.
AB  - Moclobemide is a reversible and selective inhibitor of the enzyme monoamine
      oxidase (MAO) subtype A with a broad spectrum of antidepressant activity.
      Controlled clinical studies suggest that the short term clinical efficacy of
      moclobemide is significantly superior to that of placebo, and comparable to that
      of the tricyclic antidepressants clomipramine, amitriptyline, imipramine and
      desipramine, the irreversible MAO inhibitor tranylcypromine and the second
      generation antidepressants maprotiline, mianserin and fluvoxamine in the
      treatment of major depressive illness. Moclobemide appears to be equally
      effective in endogenous and nonendogenous depression, producing marked
      amelioration of clinical features of psychomotor retardation and depressed mood.
      Moclobemide is well tolerated, being largely devoid of the anticholinergic
      adverse effects, symptomatic postural hypotension and weight gain variously
      associated with the tricyclic antidepressants and irreversible MAO inhibitors,
      and appears considerably safer on overdosage than the tricyclic and second
      generation antidepressants. Moreover, moclobemide offers the advantage over the
      older, irreversible MAO inhibitors of causing only minimal potentiation of the
      pressor response to dietary tyramine (the so-called 'cheese effect').
      Consequently, the risk of potentially fatal hypertensive crisis, a major
      deterrent to the wider acceptance of these earlier compounds, is substantially
      reduced with moclobemide, and the need for dietary precautions is minimised. With
      its efficacy against endogenous and nonendogenous depression, relatively rapid
      onset of antidepressant activity, and absence of carry-over effects on treatment
      withdrawal, moclobemide is likely to make an important contribution to the
      treatment of major depressive illness. Its favourable tolerability profile,
      safety on overdosage and beneficial effect on age-related cognitive impairment
      may be of particular value in the elderly and those with concurrent physical
      illness.

PMID- 1377120
TI  - Acitretin. A review of its pharmacology and therapeutic use.
AB  - Acitretin (etretin), a second generation monoaromatic retinoid for use in the
      treatment of severe psoriasis and other dermatoses, is the major active
      metabolite of etretinate and possesses a similar therapeutic index; i.e. a
      similar ratio of clinical efficacy to adverse effects. When used alone at a
      maintenance dosage of 30 to 50mg daily, acitretin is effective in the treatment
      of psoriasis, causing a reduction in the severity of scaling, erythema and
      induration. Efficacy appears to be further enhanced by combination with psoralen
      ultraviolet A photochemotherapy (PUVA) or ultraviolet B irradiation (UVB). These
      combinations reduce the time to lesion clearance and reduce the total radiation
      dose, improving overall safety. Comparative studies have confirmed the
      equivalence of acitretin and etrtinate with regard to efficacy and toxicity.
      Adverse reactions are dose-related and generally typical of hypervitaminosis A.
      Alopecia and mucocutaneous symptoms such as cheilitis and drying of the mucous
      membranes are particularly prevalent. Hypertriglyceridaemia and elevation of
      cholesterol levels also occur. Examination of the pharmacokinetic profile of
      acitretin reveals its main advantage over etretinate. Acitretin is less
      lipophilic than etretinate, and its lack of sequestration into 'deep' fatty
      storage sites is reflected in a comparatively short terminal elimination half
      life of 50 to 60 hours, compared with 120 days for etretinate. Due to its
      teratogenic potential, acitretin is strictly contraindicated in women of
      childbearing potential unless effective contraceptive measures are employed.
      Etretinate has been identified in plasma samples of some patients treated with
      acitretin. Thus, acetretin has an established place in the treatment of
      keratinising disorders, although its use in women of child-bearing potential must
      be accompanied by effective contraceptive measures, with a further 2-year
      contraceptive period after therapy completion.

PMID- 1377121
TI  - Prostaglandin E1 inhibits collagenase gene expression in rabbit synoviocytes and
      human fibroblasts.
AB  - Cartilage breakdown, as seen in inflammatory and degenerative joint diseases, can
      be mediated by proteolytic enzymes, such as the metalloproteinase collagenase,
      the only enzyme able to digest collagen at neutral pH. In vitro collagenase gene
      expression can be stimulated by the phorbol ester tumor promoter 12-O
      tetradecanoyl-phorbol-13-acetate. We have investigated the effect of
      prostaglandin E1 (PGE1) on 12-O-tetradecanoyl-phorbol-13-acetate-stimulated
      collagenase mRNA levels in the rabbit synoviocyte cell line HIG-82. PGE1, but not
      PGE2 or PGF2 alpha, was able to selectively reduce collagenase mRNA levels in a
      dose-dependent fashion. PGE1 markedly increased intracellular levels of cAMP,
      while PGE2 and PGF2 alpha had little or no effect on cAMP production in the HIG
      82 synoviocytes. Agents known to increase intracellular cAMP levels, such as the
      adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl
      1-methylxanthine (IBMX), mimicked the effect of PGE1, on collagenase mRNA levels.
      PGE1, forskolin, and IBMX also decreased collagenase mRNA levels in human skin
      fibroblasts, demonstrating that this observation was not unique to the HIG-82
      cell line. Transient transfection experiments carried out in HIG-82 cells using a
      1.2-kilobase portion of the 5'-flanking region of the human collagenase gene
      linked to the reporter gene luciferase demonstrated that PGE1, forskolin, and
      IBMX exert their inhibitory effect on the promoter region of the collagenase
      gene.

PMID- 1377122
TI  - Not all insulin-like growth factor-binding proteins (IGFBPs) are detectable by
      western ligand blotting: case studies of PC12 pheochromocytoma and rat anterior
      pituitary IGFBPs and proteolyzed IGFBP-3.
AB  - We studied the limitations of the Western ligand blot (WLB) for detecting insulin
      like growth factor-binding proteins (IGFBPs). PC12 rat pheochromocytoma cells and
      rat anterior pituitary cells (AP) secrete IGFBPs that cannot be detected by WLB.
      We used affinity labeling, WLB, dot blotting, competitive binding, ion exchange
      chromatography, and deglycosylation to characterize these IGFBPs. These IGFBPs
      were compared with pregnancy protease-derived IGFBP-3 fragments that also bind
      insulin-like growth factors (IGFs), but are not detectable by WLB. We showed that
      PC12 IGFBP is cationic, not glycosylated, with 25,500 mol wt reduced (18,500
      unreduced), with high affinity for IGF-II and low affinity for IGF-I. It cannot
      be detected by WLB and is not a proteolytic derivative of other IGFBPs or IGF-II
      receptors. Its binding activity is not destroyed by sodium dodecyl sulfate (SDS)
      and heating. It binds to nitrocellulose and IGF-II after dot blotting, but not to
      IGF-II during WLB. AP also secrete an IGFBP(s) that was not detectable by WLB. AP
      IGFBPs, unlike those of PC12, have a higher mol wt, and at least one component is
      glycosylated. The failure of WLB to detect these proteins remains unexplained.
      Pregnancy protease-derived IGFBP-3 fragments also bind IGFs and are not
      detectable by WLB. However, they do electrotransfer to nitrocellulose. The
      failure of WLB to detect these fragments is probably due to proteolysis rendering
      the binding site susceptible to irreversible denaturation (under conditions of
      WLB) during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These data
      suggest that WLB, while valuable, may have significant limitations in specific
      cases. Other techniques must complement WLB for detection of IGFBPs in
      conditioned media and other biological specimens.

PMID- 1377123
TI  - Mitogenic effect of a factor from rat somatomammotrophs on mammary epithelial
      cells.
AB  - We have previously established a somatomammotroph cell line (rPC0) derived from
      normal rat pituitary that secretes GH and PRL. In this study we report that
      conditioned medium from rPC0 cells (CM-rPC0) exhibited a stimulatory effect on
      the growth of rat mammary epithelial cells in culture. Fractionation of CM-rPC0
      revealed that the growth-promoting activity of CM-rPC0 was associated with a
      fraction eluting from a diethylaminoethyl-Sephacel column at 0.5 M NaCl. The
      growth-promoting activity of this fraction was abolished by trypsin and was
      resistant to dithiothreitol treatment. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis showed that the predominant components of the 0.5-M NaCl fraction
      were proteins migrating at the 14-18K region of the gel. The 0.5-M NaCl fraction
      did not contain immunodetectable GH or PRL. Further fractionation of CM-rPC0 on a
      heparin-agarose column showed that the growth-promoting activity eluted at 0.9 M
      NaCl. The two predominant proteins in this fraction had apparent mol wt of 14.5K
      and 18.2K. Based on the structural and biological properties, several known
      hormones and growth factors were excluded from consideration as potential
      candidates responsible for the growth-promoting effect of the 14-18K proteins. It
      is postulated that this group of 14-18K proteins contains a new factor(s) that
      affects the growth of mammary epithelial cells.

PMID- 1377124
TI  - Expression of a lactogen-dependent insulin-like growth factor-binding protein in
      cultured mouse mammary epithelial cells.
AB  - The ability of normal mouse mammary epithelial cells (MECs) to express insulin
      like growth factor-binding proteins (IGFBPs) was examined. MECs were isolated
      from day 11 pregnant mice and cultured on floating collagen gels in serum-free
      basal medium. After 24 h, the medium was replaced with fresh medium with/or
      without mouse PRL (mPRL), mouse placental lactogen-I (mPL-I), mPL-II, mouse GH
      (mGH), IGF-I, and IGF-II, either alone or in combinations. The MECs were cultured
      for an additional 5 days before collection of conditioned medium (CM). The
      relative amount of IGFBPs present in the CM was determined by Western ligand
      blotting, and alpha-lactalbumin content was determined with a specific RIA. The
      CM of the MECs contained two IGFBPs, with approximate mol wt of 29K and 40-45K.
      The 40-45K IGFBP appears to be the mouse equivalent of IGFBP-3, but the identity
      of the 29K IGFBP is not presently known. The 29K IGFBP was not N-glycosylated and
      did not cross-react with antiserum to rodent IGFBP-2 or human IGFBP-1. Basal
      IGFBP expression was very low, but the addition of mPL-I, or mPL-II stimulated a
      marked increase in the amount of 29K IGFBP that was released into the CM and a
      lesser increase in the release of IGFBP-3. This increase in the release of 29K
      IGFBP was dose dependent, with increases found at concentrations as low as 1
      ng/ml lactogen. mGH also stimulated the release of 29K IGFBP, but was less potent
      than any of the three lactogens. Treatment of MECs with either IGF-I or IGF-II
      increased the amount of both the 29K IGFBP and IGFBP-3 in the CM, with relative
      potencies similar to those of the lactogenic hormones. However, when either IGF-I
      or IGF-II was added together with one of the lactogenic hormones, the release of
      29K IGFBP was increased in an additive manner. While the IGFs acted additively
      with the lactogenic hormones on the expression of 29K IGFBP, they did not
      stimulate alpha-lactalbumin production by the MECs or act to enhance the effects
      of the lactogenic hormones in stimulating alpha-lactalbumin production. This
      study demonstrates that IGFBPs are expressed in normal mouse MECs, and the
      release of these IGFBPs into the CM is hormonally regulated by both lactogenic
      hormones and IGFs.

PMID- 1377125
TI  - Insulin-like growth factor binding protein (IGFBP)4 accounts for the connective
      tissue distribution of endothelial cell IGFBPs perfused through the isolated
      heart.
AB  - Insulin-like growth factor binding protein 4 (IGFBP4) was purified to homogeneity
      from conditioned media of bovine pulmonary artery endothelial cells and shown to
      have the N-terminal amino acid sequence DEAIHCPPCS, a sequence unique to IGFBP4.
      The IGFBP4 was separated into predominantly glycosylated and nonglycosylated
      fractions, with each fraction separately perfused through isolated, beating rat
      hearts. Both forms of IGFBP4 crossed the capillary boundary of the heart and
      distributed primarily in subendothelial connective tissue components with a
      connective tissue/cardiac muscle distribution ratio of 20:1 for the glycosylated
      fraction and 27:1 for the nonglycosylated fraction. Perfused IGFBP1, 2, 3, and
      IGF-I also crossed the capillary boundary but in contrast to IGFBP4,
      preferentially localized in cardiac muscle with a connective tissue/muscle ratio
      of approximately 1:3. We conclude that the connective tissue distribution
      previously reported for IGFBPs in conditioned media of pulmonary artery
      endothelial cells is due to IGFBP4.

PMID- 1377127
TI  - The role of the oligosaccharide chains of thyrotropin alpha- and beta-subunits in
      hormone action.
AB  - TSH, a dimeric glycoprotein hormone, has two N-linked complex-type
      oligosaccharide chains on the alpha-subunit and one on the beta-subunit. The
      oligosaccharide chains of TSH are important for the expression of hormonal
      activity, but the contribution of those on each of the subunits to the activity
      is not clear. In the current study we have determined the relative importance of
      the oligosaccharide chains of TSH subunits using a recently reported method of
      enzymatic deglycosylation. The alpha- and beta-subunits of bovine TSH were
      deglycosylated with endoglycosidase-F and recombined to obtain differentially
      deglycosylated TSH. The derivatives showed no differences in their receptor
      binding activities. The in vitro bioactivity of these derivatives was assessed by
      measuring adenylyl cyclase activity in bovine thyroid membranes and stimulation
      of cAMP production and growth in FRTL-5 cells. In the adenylyl cyclase assay,
      deglycosylation of the alpha-subunit alone had a more profound effect on the
      activity [maximal stimulatory activity (Vmax), 13% that of alpha.beta) than when
      the beta-subunit alone was deglycosylated (Vmax, 50% that of alpha.beta). In the
      FRTL-5 assays, removal of carbohydrate from TSH alpha, but not the beta-subunit,
      caused a 2- to 3-fold increase in the concentration required for half-maximal
      stimulation, with minimal change in the apparent Vmax. The adenylyl cyclase assay
      in bovine membranes was more sensitive to carbohydrate removal than the assays of
      rat FRTL-5 cells, in which the derivatives with lower activity were able to
      stimulate cAMP and growth to near-maximal levels, albeit at 3-fold higher
      concentrations. These results indicate that the carbohydrate chains in both
      subunits of TSH, particularly those in the alpha-subunit, are important in
      hormone action. In contrast to previous reports, our study shows that the beta
      subunit plays a role in signal transduction.

PMID- 1377126
TI  - Angiotensin II receptor-mediated calcium influx in bovine adrenal glomerulosa
      cells.
AB  - The cytoplasmic calcium ([Ca2+]i) response to angiotensin II (AII) in bovine
      adrenal glomerulosa cells is characterized by an initial transient peak due to
      intracellular Ca2+ mobilization, followed by a sustained plateau phase that is
      dependent on Ca2+ entry from the extracellular fluid. In Fura-2 loaded cells, the
      calcium channel antagonists, nifedipine (1 microM) and verapamil (20 microM),
      only partially reduced the cytosolic calcium profile induced by AII. The
      dihydropyridine agonist, Bay K 8644, caused a moderate increase in [Ca2+]i when
      added in concentrations of 50-100 nM, but did not enhance the AII-induced rise in
      [Ca2+]i. These results indicate that most of the AII-stimulated Ca2+ influx is
      through channels that are insensitive to dihydropyridines and verapamil. In
      contrast, the inorganic Ca2+ channel blocker, LaCl3 (10 microM), inhibited the
      AII-induced plateau phase by more than 50%. The AII-induced Ca2+ signal was not
      affected by treatment with pertussis toxin (100-300 ng/ml for 12 h). The prior
      addition of specific AII-antagonists (DuP 753, a nonpeptide antagonist, and three
      peptide analogs, [Sar1,Thr8]AII, [Sar1,Ala8]AII, and [Sar1,Ile8]AII) completely
      inhibited the AII-induced Ca2+ signal. However, addition of up to 25,000 molar
      excess of these antagonists at intervals from 10 sec to 5 min after AII caused
      progressively less attenuation of the sustained Ca2+ signal. After 5 min,
      addition of antagonists did not inhibit the agonist-induced Ca2+ response for up
      to 20 min. The progressive loss of ability of the antagonists to inhibit the
      sustained elevation of [Ca2+]i could reflect prolonged activation of the receptor
      or of a subsequent process that maintains Ca2+ influx despite receptor blockade.
      It is possible that sequestration and/or endocytosis of the AII-receptor complex
      is accompanied by continued generation of intracellular signals that contribute
      to the maintenance of the [Ca2+]i response.

PMID- 1377128
TI  - Effect of epithelium removal and of enkephalin inhibition on the
      bronchoconstrictor response to three endothelins of the human isolated bronchus.
AB  - The three endothelins ET-1, ET-2 and ET-3 induced a potent contractile response
      in the human isolated bronchus with an intact epithelium, which proceeded on two
      different stages. The first stage was observed at low concentrations (high
      potency) (10(-12) to 10(-9) M) but corresponded to a low intrinsic activity (Emax
      maximal effect induced by ACh 10(-3) M), the second stage appeared at higher
      concentrations and corresponded to higher intrinsic activity. The rank order of
      potency for the two stages of contractile activity was ET-1 greater than ET-2 =
      ET-3. Removal of the epithelium significantly enhanced the two stages of the
      contractile responses to the three endothelins and abolished the differences in
      potency efficacy that were observed between ET-1, ET-2 and ET-3 when the
      epithelium was present. Phosphoramidon (10(-5) M), an enkephalinase inhibitor,
      was as potent as epithelium removal in enhancing the contractile responses to
      these agonists at low concentrations (first stage of contraction, 10(-16) to 10(
      9) M). However, with high concentrations of endothelins (greater than 10(-9) M,
      second stage of contraction), phosphoramidon was less potent than epithelium
      removal in enhancing the contractile responses. In epithelium-denuded strips,
      preincubation with phosphoramidon did not further increase the maximal
      contractions induced by/or the potencies of ET-1, ET-2 or ET-3. After epithelium
      removal, responses to low doses of endothelins were attenuated by nicardipine
      (10(-6) M) whereas responses to high doses of the endothelins were not affected,
      as was also observed when the epithelium was present. (ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377129
TI  - Tachykinin-induced dyspnea in conscious guinea pigs.
AB  - Aerosol administration of neurokinin A (NKA) or substance P (SP) to conscious
      guinea pigs produced labored abdominal breathing (dyspnea). Time to onset of
      dyspnea was inversely related to tachykinin concentration. Aerosol administration
      of the neutral endopeptidase inhibitor thiorphan significantly potentiated
      tachykinin-induced dyspnea without affecting responses to leukotriene D4 (LTD4),
      carbachol, histamine, platelet activating factor or serotonin (5-HT), indicating
      selectivity for tachykinins rather than a nonspecific effect on agonist
      reactivity. The rank order of potency for producing dyspnea was LTD4 greater than
      or equal to NKA (with thiorphan) much greater than SP (with thiorphan) greater
      than 5-HT = carbachol greater than histamine greater than platelet-activating
      factor. Pretreatment with propranolol, phentolamine, methysergide, pyrilamine or
      the peptide leukotriene antagonist, ICI 198,165, did not alter dyspnea induced by
      NKA or SP. The dose-response curves for NKA and SP were shifted to small degrees
      (less than 3-fold) to the right by atropine and to the left by indomethacin.
      Also, pretreatment with capsaicin did not affect responses to NKA or SP,
      indicating that they do not cause dyspnea by activating capsaicin sensitive C
      fibers. These results suggest primarily direct effects of NKA and SP. This model
      may be useful for in vivo evaluation of tachykinin antagonists.

PMID- 1377130
TI  - Effect of 3-isobutyl-1-methylxanthine and zaprinast on non-adrenergic non
      cholinergic relaxation in the rat gastric fundus.
AB  - Vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) have been proposed
      as inhibitory non-adrenergic non-cholinergic (NANC) neurotransmitters in the rat
      gastric fundus. The smooth muscle relaxant actions of VIP and NO are medaited by
      cAMP and cGMP, respectively; therefore the effect of inhibitors of
      phosphodiesterases responsible for cyclic nucleotide breakdown on relaxation
      induced by VIP, NO and electrical field stimulation was investigated. The non
      specific phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), the
      cGMP-specific phosphodiesterase inhibitor, zaprinast, the adenylate cyclase
      activator, forskolin, and the cyclic nucleotide analog, 8-bromo cGMP, produced
      concentration-dependent relaxation of rat gastric fundus strips precontracted by
      PGF2 alpha. IBMX potentiated isoprenaline-induced relaxation but not relaxation
      induced by sodium nitroprusside, VIP, NO or electrical field stimulation.
      Zaprinast potentiated the relaxation induced by sodium nitroprusside, while
      having no influence on relaxation due to any other stimulus. The combination of
      both phosphodiesterase inhibitors did not significantly affect the electrically
      induced relaxation. It is concluded that both cAMP and cGMP mediate relaxation in
      the rat gastric fundus. Further research is needed to investigate the role of the
      cyclic nucleotides during NANC relaxation of this tissue.

PMID- 1377131
TI  - Phorbol esters induce transient changes in the accessibility of the carboxy
      terminal domain of nuclear lamin A.
AB  - Treatment of human epithelial cells in culture with phorbol esters (TPA) gives
      rise to a transient and reversible loss of accessibility to antibodies of the
      nonhelical carboxy-terminal domain of nuclear lamin A that distinguishes it from
      lamin C. No change in the accessibility of epitopes present in the common domain
      of lamins A and C was observed. Loss of accessibility of lamin A was not due to
      proteolytic degradation nor to modification of the isoelectric point of lamin A
      and did not depend upon protein kinase C activation nor protein synthesis.
      Perturbation of desmosome organization by growth in low calcium blocked the
      effect of TPA on lamin A. Prolonged exposure to nocodazole, one of the effects of
      which is a perinuclear collapse of intermediate filaments, also blocked the
      effect of TPA on lamin A. These results suggest that the initial target of TPA
      may be at the level of cell-cell contacts and that the perturbation induced by
      TPA may be propagated via the structural link formed by intermediate filaments
      between the cell surface and the nucleus, giving rise to a change in conformation
      of the carboxy-terminal domain of lamin A or to an interaction of this domain
      with another nuclear component. These results form the basis for the hypothesis
      that the interphase nuclear lamina may play an active role in the process of
      mechanochemical signal transduction.

PMID- 1377132
TI  - Alpha IIb beta 3 integrin expression and function in subpopulations of murine
      tumors.
AB  - Subpopulations of B16 amelanotic melanoma (B16a) cells, isolated by centrifugal
      elutriation from enzymatically dispersed solid tumors, demonstrated different
      abilities to form lung colonies when injected intravenously. In contrast, no
      differences in experimental metastasis were observed among subpopulations
      obtained from Lewis lung (3LL) tumors. Lung colonization by B16a and 3LL
      subpopulations correlated positively with observed differences (B16a) or lack of
      differences (3LL) in tumor cell ability to induce aggregation of homologous
      platelets, to adhere to subendothelial matrix or fibronectin, and with the
      percentage of cells in the G2/M phase of the cell cycle. Both B16a and 3LL cells
      express alpha IIb beta 3 integrin receptors; however, differences in the receptor
      expression level were found only among B16a subpopulations. Comparison of the
      amount of alpha IIb beta 3 receptor expressed on cell surface with tumor cell
      ability to induce platelet aggregation (TCIPA) and to adhere to fibronectin or
      subendothelial matrix revealed a positive correlation. Pretreatment of tumor
      cells with alpha IIb beta 3-specific antibodies inhibited tumor cell matrix
      adhesion, TCIPA, and lung colony formation. We propose that alpha IIb beta 3
      integrin receptor expression, tumor cell matrix adhesion, and tumor cell-induced
      platelet aggregation can be important parameters to indicate the metastatic
      potential of some tumor cells and that the alpha IIb beta 3 is a multifunctional
      receptor involved in both tumor cell-matrix and tumor cell-platelet interactions.
      Further, the correlation among cell cycle phase, metastatic ability, and receptor
      expression suggests that metastatic propensity may be transiently expressed
      and/or increased in some tumor cell subpopulations.

PMID- 1377133
TI  - Immunocytochemical analysis reveals differences between the subcellular
      localization of normal and delta Phe508 recombinant cystic fibrosis transmembrane
      conductance regulator.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene coding for the cystic
      fibrosis transmembrane conductance regulator (CFTR). The most common mutation
      responsible for CF is the deletion of amino acid residue Phe508, with an average
      allelic frequency of 70%. We have isolated an anti-CFTR monoclonal antibody which
      specifically recognizes recombinant normal and delta Phe508-CFTR produced by a
      vaccinia virus expression system. Immunocytochemical analysis of L cells
      expressing either normal or delta Phe508-CFTR showed a marked difference in
      subcellular distribution. Normal CFTR had a distinct localization in the
      perinuclear area and was also associated with the plasma membrane. delta Phe508
      CFTR essentially lacked the membrane-associated distribution and was present
      throughout the cytoplasm. This heterologous expression system thus provides a
      model system for studying the subcellular localization of different mutant forms
      of CFTR.

PMID- 1377134
TI  - Increased expression of cytokeratin and ferritin-H genes in tumorigenic clones of
      the SW 613-S human colon carcinoma cell line.
AB  - Subclones of the SW 613-S human colon carcinoma cell line differ by their ability
      to induce tumors in nude mice and by their level of amplification of the c-myc
      gene. Clones with a high level of amplification are tumorigenic in nude mice
      whereas those with a low level are not. Genes overexpressed in the tumorigenic
      clones as compared to the nontumorigenic ones were searched by differential
      screening of a cDNA library. Two cDNA clones corresponding to cytokeratin K18 and
      ferritin-H chain were isolated. The steady state level of the corresponding mRNAs
      is higher in cells of all tumorigenic clones. The level of cytokeratin K8 mRNA,
      the specific partner of cytokeratin K18 in intermediate filaments of epithelial
      cells, is also elevated in these cells. For all three genes, this is mainly due
      to an increase in the transcription rate, as shown by a nuclear run-on assay.
      Immunoblotting experiments showed that cytokeratins K8, K18, and K19 are more
      abundant in cells of tumorigenic clones. The mRNA of the other subunit of apo
      ferritin (ferritin-L chain) is expressed at the same level in both types of
      clones. The mRNAs of cytokeratins K18 and K8 and of ferritin-H chain are also
      overexpressed in cells of nontumorigenic clones which have acquired a tumorigenic
      phenotype after transfection of c-myc gene copies.

PMID- 1377135
TI  - The Ca2+ release channel in junctional sarcoplasmic reticulum: gating and
      blockade by cations.
AB  - 1. By using a sarcoplasmic reticulum preparation containing feet structures and
      the 45Ca2+/filtration technique, the opening and closing response of the Ca(2+)
      channel was studied. 2. Extravesicular Sr2+ can activate the channel even though
      this cation is less efficient than Ca2+ in stimulating the Ca2+ release. Higher
      Sr2+ concentrations display inhibitory action. 3. By studying the closing
      response high- and low-affinity cations can be distinguished, according to the
      concentration range required to exert their effect. 4. The synergistic behavior
      observed by combining high- and low-affinity blocking cations suggest that they
      interact through the same binding site. 5. The high-and low-affinity cations are
      noncompetitive blockers of the activating Ca2+ suggesting the existence of an
      inhibitory site which is different to the activating site.

PMID- 1377136
TI  - Nutrition and somatomedin XXIX. Molecular regulation of IGFBP-1 in hepatocyte
      primary culture.
AB  - The insulinlike growth factors (IGFs) circulate in association with insulinlike
      growth factor binding proteins (IGFBPs) that modulate IGF action, but mechanisms
      of IGFBP regulation are poorly understood. We investigated the regulation of
      IGFBPs in primary cultures of rat hepatocytes, measuring the appearance of export
      proteins by ligand blotting after separation via SDS/PAGE, and evaluating mRNA
      with cDNA probes. Northern blotting studies revealed that IGFBP-1 was expressed
      at high levels in cultured hepatocytes, in which sustained release of both
      insulinlike growth factor I and albumin marks preservation of differentiated
      status. In contrast, transcripts of IGFBP-3 and IGFBP-2 were not detected.
      Release of IGFBP-1 was unaffected by exposure to glucose (20-500 mg/dl) or to
      provision of amino acids (0.25-6.25 times normal rat arterial plasma levels).
      Hormonal studies revealed little effect of glucagon, inhibition by insulin,
      stimulation by dexamethasone, and blunting of dexamethasone effects by added
      insulin. Adding dexamethasone provided progressive stimulation: 5-, 11-, and 26
      fold at 10(-9), 10(-8), and 10(-7) M, all P less than 0.01; increases in IGFBP-1
      protein (ligand blot) and IGFBP-1 mRNA (Northern blot) were highly correlated (r
      = 0.62, P less than 0.001). In contrast, adding insulin resulted in progressive
      suppression of both IGFBP-1 protein and IGFBP-1 mRNA, 43% at 10(-10) M, 74% at
      10(-9) M, and 83% (maximal) at 10(-8) M; ED50 of approximately 10(-10) M is
      within the physiological range of insulin concentrations.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1377138
TI  - Non-verbal communication skills of surgically treated children with infantile
      spasms.
AB  - The authors present preliminary findings on the effects of surgery on the
      development of early non-verbal social communication skills in eight children
      with intractable infantile spasms. After a mean follow-up of 15.2 months, there
      was no statistically significant change in the post-surgical non-verbal
      communication behavior of these children beyond the expected developmental
      change. Implications of these findings for the developmental impairment
      associated with infantile spasms are discussed.

PMID- 1377137
TI  - Experimental diabetic neuropathy. Effect of ganglioside treatment on axonal
      transport of cytoskeletal proteins.
AB  - Abnormalities in axonal transport of proteins are thought to play an important
      role in the pathogenesis of diabetic neuropathy. Gangliosides exert a positive
      action on numerous alterations in biochemistry and physiology of diabetic nerves.
      This study was undertaken to assess the effects of exogenous gangliosides on the
      axonal transport of structural proteins such as actin and tubulin in the sensory
      fibers of short-term (9-wk) and long-term (6-mo) diabetic rats. Adult Sprague
      Dawley rats were made diabetic with a single injection of 70 mg/kg streptozocin
      i.p. Subgroups were injected daily with either highly purified ganglioside
      mixture (10 mg/kg i.p.) or saline for 1 mo, beginning either 2 or 17 wk after
      streptozocin injection. Age-matched rats were used as controls. Axonal transport
      was studied by the pulse-labeling technique. Three weeks after labeling, sciatic
      nerves were dissected out and processed for sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and fluorography. In diabetic rats of both experimental
      designs, the transport rate of tubulin and actin was decreased by approximately
      30% compared with control rats. Ganglioside treatment counteracted such
      alterations in both 9-wk and 6-mo diabetic rats. These data suggest a
      pharmacological effect that could be correlated with molecular interactions
      between integral membrane glycolipids and cytoskeletal elements.

PMID- 1377139
TI  - Transient increase in renal insulin-like growth factor binding proteins during
      initial kidney hypertrophy in experimental diabetes in rats.
AB  - The insulin-like growth factors, insulin-like growth factor I and insulin-like
      growth factor II are bound to six distinct classes of insulin-like growth factor
      binding proteins (IGFBPs) in the circulation and in extracellular fluids.
      Diabetic renal hypertrophy is preceded by a transient increase in kidney insulin
      like growth factor I suggestive of a renotropic function for insulin-like growth
      factor I. In order to examine a possible involvement of IGFBPs in initial
      diabetic kidney growth and in kidney insulin-like growth factor I accumulation,
      we studied rat kidney IGFBPs by ligand blotting during the first 4 days after
      induction of diabetes. Six distinct bands were identified in kidney and liver
      tissue with apparent molecular weight values of 38-47 (doublet), 34, 30, 24 and
      20 kDa. The 38-47 kDa doublet band probably corresponds to the insulin-like
      growth factor binding subunit of IGFBP-3, the 24 kDa band to IGFBP-4 and the 30
      kDa band to IGFBP-1 and/or IGFBP-2, as these IGFBPs in rats have similar
      molecular weight. In untreated diabetic rats a transient increase in the kidney
      30 kDa band was demonstrable 24 h after induction of diabetes with a maximal rise
      (two-fold) after 48 h, followed by a decrease to baseline values after 4 days. In
      untreated diabetic rats the 38-47 kDa doublet band also increased (two-fold) in
      kidney during the first 2 days after induction of diabetes, followed by a
      subsequent decrease. Insulin-treatment prevented both the increase in the 30 kDa
      and in the 38-47 kDa bands.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377140
TI  - ATP-dependent bacterial transporters and cystic fibrosis: analogy between
      channels and transporters.
AB  - The traffic ATPases superfamily includes known transporters, both prokaryotic and
      eukaryotic, including the medically important proteins, P-glycoprotein, and the
      cystic fibrosis gene product (CFTR), which is known to be a Cl- channel. The
      structure and mechanism of action of the best-studied members of the superfamily,
      the periplasmic permeases, are described and related to that of CFTR and
      eukaryotic traffic ATPases in general. The contention is put forward that the
      distinction between the architecture and mechanisms of action of channels and
      transporters is blurred.

PMID- 1377141
TI  - Long-term culture of normal human colonic epithelial cells in vitro.
AB  - Studies of normal cellular function as well as the understanding of cellular
      mechanisms of carcinogenesis and other diseases of the large intestine have been
      limited, particularly due to the lack of long-term culture of normal human large
      intestinal epithelial cells (NHLIEC). Using the epithelia from surgically
      resected human colon, we have dissociated a sufficient number of viable NHLIEC
      and maintained them in in vitro culture for up to 5 months. Normal-appearing
      human large intestinal mucosal fragments (1 mm2) were treated with 0.01 mg/ml
      trypsin, 0.2 mg/ml collagenase + 0.1 mM EGTA or 0.1 mg/ml trypsin + 0.1 mM EGTA
      in a Stomacher laboratory blender to isolate the cells. Compared with other
      methods, the use of the Stomacher blender combined with low concentrations of
      proteolytic enzymes yielded greater numbers of cells per gram of tissue, with up
      to 84% viable cells. Primary and serially passaged NHLIEC were cultured in CMRL
      1066, MEM with 5% serum, and serum-free KGM. These media were all supplemented
      with insulin, hydrocortisone, epithelial growth factor, and bovine pituitary
      extract. CMRL-1066 was found to be the best medium for NHLIEC. Contaminating
      fibroblasts were selectively removed by briefly allowing the cells to adhere to
      the culture vessel and adding 25 U/ml collagenase to the culture media at the
      first subculture treatment. The epithelial nature and secretory function of the
      established cells were confirmed by morphological criteria (light microscopy,
      phase contrast microscopy and electron microscopy), immunoreactivity to
      cytokeratin, and positive mucin cytochemistry. We propose that using this
      methodology for the culture and maintenance of NHLIEC for an extended period of
      time would serve as a valuable model for a variety of investigations.

PMID- 1377142
TI  - Fine specificity of the human T-cell response to the hepatitis B virus preS1
      antigen.
AB  - The T-cell response to hepatitis B virus envelope antigens was studied in 11
      hepatitis B vaccine recipients; 7 were selected to analyze the fine specificity
      of the T-cell response to the preS1 antigen. Four distinct T-cell epitopes were
      identified by peripheral blood lymphomononuclear cell stimulation with a panel of
      short synthetic peptides covering the preS1 sequence. The immunodominance of the
      preS1 epitopes included within peptides 21-30 and 29-48 was shown by their
      capacity to restimulate an HLA class II restricted proliferative response of T
      cells primed with the whole preS1 antigen. Conversely, peptide-specific T cells
      selected by peripheral blood lymphomononuclear cell stimulation with peptides 21
      30 and 29-48 were able to recognize the native preS1 molecule, confirming that
      these epitopes are actually generated by the intracellular processing of preS1.
      Finally, amino acid residues essential for T-cell activation by peptide 21-30
      were identified using 10 analogues of the stimulatory peptide containing single
      alanine substitutions. These results may be relevant to the design of efficient
      synthetic vaccines against hepatitis B virus infection.

PMID- 1377143
TI  - Recurrent and acquired hepatitis C viral infection in liver transplant
      recipients.
AB  - To examine the postliver transplant recurrence of hepatitis C virus (HCV)
      infection in patients with pretransplant infection, as well as its acquisition in
      patients without prior infection, we used the polymerase chain reaction to
      amplify HCV RNA in serum and/or liver samples of 89 patients with alcoholic and
      cryptogenic cirrhosis undergoing liver transplantation. Results were correlated
      with histologic findings from posttransplant liver biopsies. Ninety-five percent
      of patients with pretransplant infection had posttransplant viremia. In contrast,
      35% of patients without pretransplant infection acquired the virus (P less than
      0.0001). Pretransplant HCV infection predisposed patients to hepatitis in the new
      graft. HCV RNA was present in serum of 96% of patients with posttransplant
      hepatitis. Fifty-six percent of patients with posttransplant HCV infection had no
      evidence of liver damage at least 1 year posttransplant. However, of those
      patients with histologic hepatitis, chronic active hepatitis was common. It is
      concluded that although HCV infection recurs posttransplant in almost all
      infected patients, acquisition of the HCV infection with transplant is common.
      Pretransplant HCV infection is an independent risk factor for the development of
      posttransplant hepatitis. HCV infection accounts for the majority of
      posttransplant hepatitis not due to cytomegalovirus, and although many patients
      with posttransplant viremia have little evidence of histologic hepatitis,
      significant hepatic damage may occur.

PMID- 1377144
TI  - Genomic variation of hepatitis C virus: clues to clinical variation?

PMID- 1377145
TI  - The lipase/amylase ratio: sensitive but not specific.

PMID- 1377146
TI  - Lipase/amylase ratio in pancreatitis: an etiologic index?

PMID- 1377147
TI  - Palliation of obstructing gastric cancer with steel mesh, self-expanding
      endoprostheses.

PMID- 1377148
TI  - Treatment of malignant esophageal obstruction with silicone-coated metallic self
      expanding stents.
AB  - Six patients with high-grade malignant esophageal obstruction were treated with
      silicone-coated metallic self-expanding esophageal stents (Z stents). Endoscopic
      placement of stents was well tolerated. All patients achieved excellent
      palliation, defined by a decrease of at least two dysphagia grades, which was
      sustained. Complications occurred during follow-up in four patients and included
      stent migration, silicone disruption with tumor ingrowth, food impaction, and
      perforation (discovered at autopsy) at the distal stent site. Three of the four
      complications were promptly treated by endoscopic or radiologic intervention.
      Recent modification in stent design and placement technique will hopefully reduce
      complications. The self-expanding stent has several theoretical advantages over
      the rigid plastic stent and Nd:YAG laser for palliation of obstructing esophageal
      malignancy.

PMID- 1377149
TI  - Self-expanding metal stents for esophageal and gastric cancer: a new opening.

PMID- 1377150
TI  - [Continuous ambulatory intravenous morphine infusion for pain therapy in advanced
      ovarian cancer].
AB  - We report on a female outpatient with cancer of the ovary, who received
      continuous intravenous morphine infusion for terminal pain control. The patient
      was treated over a period of 48 days with a morphine dosage ranging from 10 to 60
      mg/h, which kept her free of pain. With treatment, she was alert, communicative
      with her relatives and moved freely. At a later stage, we complemented the
      treatment with Diazepam and Haloperidol. No side-effects were observed over the
      whole period of morphine infusion.

PMID- 1377151
TI  - Streptomycin biosynthesis and its regulation in Streptomycetes.
AB  - New insights into the gene orders, structures, evolution, and functions of
      streptomycin (Sm) biosynthetic genes (str) were gained via hybridization studies,
      determination of nucleotide sequences, and measurement of expression in the str
      gene clusters of Streptomyces griseus and S. glaucescens. Both str clusters
      showed considerable divergence in macro and micro structure. Genes putatively
      involved in pathways leading to the (dihydro-)streptose and N-methyl-L
      glucosamine moieties of Sm were identified. Additional regulatory elements, such
      as gene strS and conserved TTA codons in the N-terminal sections of reading
      frames, are reported. Evidences for the involvement of physiological state,
      signal transduction, and activators in the control of Sm production are
      presented.

PMID- 1377153
TI  - Differences in the mode of the extension of gastric cancer classified by
      histological type: new histological classification of gastric carcinoma.
AB  - By combining two of the morphological characteristics of gastric cancer, the
      degree of differentiation of the glandular tubules and the amount of mucus in the
      cytoplasm, the histological type of the gastric carcinoma was categorised into
      four groups. Group I: tubular differentiation--well; mucus in cytoplasm--poor;
      group II: tubular differentiation--well; mucus in cytoplasm--rich; group III:
      tubular differentiation--poor; mucus in cytoplasm--poor; group IV: tubular
      differentiation--poor; mucus in cytoplasm--rich. A study of the relation between
      the types of primary lesion and the mode of extension and recurrence of gastric
      carcinoma in 200 autopsy cases was then undertaken. In group I, the frequency and
      extent of haematogenous metastasis such as in the liver was high, while in group
      IV, that of lymph node metastasis, direct invasion into surrounding organ, and
      peritoneal dissemination were higher. In group III, which showed the intermediate
      mode of extension in nature to those of group I and IV, although the frequency
      and severity of the bone marrow metastasis was the highest. There were
      significant differences in the modes of development and the extent of
      infiltration in all groups.

PMID- 1377152
TI  - Effect of Helicobacter pylori infection on colloidal bismuth subcitrate
      concentration in gastric mucus.
AB  - Necropsy gastric mucus infected with Helicobacter pylori has a reduced capacity
      to concentrate colloidal bismuth subcitrate when compared with non-infected
      mucus. Mucus mounted in a modified in vitro diffusion chamber was bathed with
      colloidal bismuth subcitrate solutions at different concentrations and pH levels.
      Bismuth was measured by atomic absorption spectrophotometry to assess intramucus
      colloidal bismuth subcitrate concentrations. Bismuth concentrations in non
      infected mucus were higher than in Helicobacter pylori infected mucus at all
      experimental colloidal bismuth subcitrate concentrations and pH levels.
      Regardless of the infection status, the intramucus concentration of colloidal
      bismuth subcitrate was dependent upon the concentration of the bathing solution
      and independent of the pH and the mucus thickness. Colloidal bismuth subcitrate
      solubility in saline solution varied with pH, and was least soluble in the pH
      range 1.1 to 3.25 and more soluble above and below this pH range. This study
      suggests that Helicobacter pylori infection is associated with physicochemical
      changes in the gastric mucus with a reduction in its capacity to concentrate
      colloidal bismuth subcitrate. Such a reduction may compromise the attainment of
      optimum colloidal bismuth subcitrate concentrations necessary for its
      bactericidal activity.

PMID- 1377154
TI  - Effective peritoneal therapy of acute pancreatitis in the rat with glutaryl
      trialanin-ethylamide: a novel inhibitor of pancreatic elastase.
AB  - The six hour peritoneal lavage with glutaryl-trialanin-ethylamide, a low
      molecular competitive inhibitor of pancreatic elastase (IC50-8 mumol/l),
      effectively suppresses the evolution of taurocholate induced acute pancreatitis
      in the rat. The lavage alone is followed by a marked decrease of fat necrosis and
      amylase and lipase activity in serum. The area of pancreatic haemorrhage was
      significantly reduced only after the lavage solution was supplemented with Glt
      Ala3-NHEt. The effect was not enhanced by a bolus injection of the inhibitor
      before starting the lavage. The combination of Glt-Ala3-NHEt with aprotinin or
      nafamstate mesilate produced only marginal greater benefit. The effect of Glt
      Ala3-NHEt on pancreatic haemorrhage is time and dose related even with delayed
      onset of the lavage. Animals treated with peritoneal lavage without Get-Ala3-NHEt
      lived longer than controls (p less than 0.05), but by 60 hours the survival rate
      of both groups was almost the same (76 v 74%). All animals lavaged with Glt-Ala3
      NHEt survived 120 hours and the difference in the survival rate between this and
      both remaining groups was significant (100% v 76% v 74% - p less than 0.05). The
      results were considered favourable and preliminary clinical trials of Glt-Ala3
      NHEt in subjects with acute pancreatitis justified.

PMID- 1377155
TI  - Dual sequential non-cross-resistant chemotherapy for advanced stage squamous cell
      carcinoma of the cervix.
AB  - Forty-three patients with recurrent and metastatic squamous cell carcinoma of the
      cervix received a program of sequential combination chemotherapy incorporating
      induction with cisplatin, vinblastine, and bleomycin (PVB) and subsequent
      consolidation with 5-fluorouracil, doxorubicin, cyclophosphamide, and vincristine
      (FACV). The overall response rate was 62% and 10 patients (23%) achieved complete
      remission. Response status was improved in 11 patients at the completion of FACV
      after initial PVB therapy, including 9 complete remissions. The median survival
      for all patients in the study was 38 weeks and 50 weeks for the responding
      patients. Myelosuppression was the principal toxicity encountered and 10 episodes
      of neutropenic sepsis occurred, including one septic death. However, the only
      cumulative toxicity was peripheral neuropathy, although this was only moderate to
      severe in 2 patients. These results are encouraging, but will require
      confirmation in randomized comparison to cisplatin, presently accepted as
      standard single-agent therapy.

PMID- 1377157
TI  - [Problem topics in gynecologic oncology].

PMID- 1377156
TI  - [Surgical treatment of stability problems and pain in osseous metastases of
      gynecologic tumors].

PMID- 1377158
TI  - [Treatment possibilities in malignant pleural and peritoneal effusions and
      pseudomyxoma peritonei].

PMID- 1377159
TI  - [Bleeding genital cancer].

PMID- 1377160
TI  - Conservative treatment of ectopic pregnancy and its effect on corpus luteum
      activity.
AB  - Corpus luteum activity was monitored in 15 women undergoing nonsurgical
      management of ectopic pregnancy with local methotrexate injection followed by
      alternating oral methotrexate and citrovorum factor (group A, n = 8) or local
      methotrexate injection alone (group B, n = 7). All patients initially
      demonstrated a viable corpus luteum (plasma progesterone ranged from 1.4 to 19
      ng/ml). The treatment was successful in 14, with the exception of one whose tube
      ruptured 11 days after local administration of methotrexate, despite a continuous
      decrease in beta human chorionic gonadotropin, 17 beta-estradiol and plasma
      progesterone levels. There seems to be no correlation between the success of the
      treatment and the behavior of beta human chorionic gonadotropin, 17 beta
      estradiol and plasma progesterone. Three patients from group A and two from group
      B displayed an initial rise in beta human chorionic gonadotropin following the
      initiation of the therapy, but the corpus luteum response differed. In group B
      patients, 17 beta-estradiol and plasma progesterone levels increased in parallel
      with beta human chorionic gonadotropin. Group A patients displayed a continuous
      decrease in 17 beta-estradiol and plasma progesterone levels despite the
      elevation of beta human chorionic gonadotropin, suggesting a possible effect of
      the systemic methotrexate on corpus luteum activity.

PMID- 1377161
TI  - Epitope specific antibody response against human type II collagen induced by anti
      idiotypic antibody.
AB  - A species specific epitope on human type II collagen (CII) recognized with mAb, 2
      60, was found to be localized on a cyanogen bromide-cleaved peptide (CB10) of
      human CII. To characterize the antibody response to the 2-60 epitope, we raised
      rabbit anti-idiotypic (Id) antibody against 2-60. The rabbit anti-2-60 Id
      antibody reacted not only with 2-60 mAb but also with 2-56 and 3-11 mAbs which
      were reactive with the epitopes related to the 2-60 epitope on CB10. The anti-Id
      antibody inhibited the binding of these three mAbs to human CII. Thus, rabbit
      anti-2-60 Id antibody recognized the cross-reactive idiotype expressed on 2-60, 2
      56 and 3-11. The anti-2-60 Id antibody inhibited about thirty percent of the
      binding of polyclonal anti-human CII antibody derived from DBA/1J mice, thereby
      suggesting that the 2-60 idiotype might be expressed on a major fraction of the
      anti-human CII antibody. Immunization with the rabbit anti-2-60 Id antibody
      elicited antibody response to the 2-60 epitope, in DBA/1J (H-2q, Ighc), BALB/c (H
      2d, Igha) and DBA/2 (H-2d, Ighc) mice. On the other hand, an epitope-specific
      antibody response induced by rabbit anti-Id antibody to 1-5 mAb reactive with a
      putative arthritogenic epitope on human CII was shown to be influenced by a
      single dominant gene, possibly the Igh gene. Our findings suggest that antibody
      responses against two distinct epitopes on human CII are probably regulated by
      different mechanisms.

PMID- 1377162
TI  - Microvessel quantitation and prognosis in invasive breast carcinoma.
AB  - The prognostic significance of microvessel quantitation in invasive breast
      carcinoma was analyzed in a study group that comprised 88 patients with axillary
      node-negative carcinoma and 32 patients with axillary node-positive carcinoma who
      had a minimum follow-up period of 9 years. Microvessels were identified by
      immunohistochemistry using antibodies to endothelial markers, including factor
      VIII-related antigen and blood group isoantigens (ABH). Factor VIII-related
      antigen staining provided more consistent results for microvessel quantitation
      than did staining for ABH isoantigens. The three most vascular areas within a
      tumor were selected, and the microvessels within a x200 microscopic field of each
      area were counted by two investigators simultaneously. Node-positive carcinomas
      demonstrated significantly higher microvessel counts than did node-negative
      carcinomas (mean +/- SD, 99 +/- 42 and 73 +/- 22, respectively; P less than
      .001). In node-negative carcinomas, tumors from patients who experienced distant
      recurrence had higher microvessel counts than did tumors from patients who were
      disease-free (84 +/- 19 and 70 +/- 22; P = .01). Similarly, in patients with node
      positive carcinoma, microvessel counts were considerably higher in tumors from
      patients who experienced distant recurrence than in patients who did not,
      although the difference did not reach statistical significance (113 +/- 44 and 93
      +/- 34, respectively). Among patients with node-negative carcinoma, those with a
      microvessel count of less than 84 had a recurrence rate of 20% compared with 57%
      in patients with counts greater than 84 (P = .003). Microvessel counts were
      independent of histologic parameters, ploidy status, and S-phase fraction but
      correlated with peritumoral vascular invasion. Both microvessel counts and
      vascular invasion were independent prognostic parameters by multivariate
      analysis. High vessel counts may represent increased tumor angiogenesis and are
      correlated with tumor aggressiveness. Microvessel quantitation may be an
      additional prognostic factor that, when used in conjunction with more established
      parameters, can help in appropriate patient management.

PMID- 1377163
TI  - CD56 (NKH1)-positive hematolymphoid malignancies: an aggressive neoplasm
      featuring frequent cutaneous/mucosal involvement, cytoplasmic azurophilic
      granules, and angiocentricity.
AB  - CD56 (NKH1) expression is a rare phenomenon in malignant lymphomas, mostly
      confined to those occurring in the nasal or nasopharyngeal region. In this study
      we provide a detailed clinicopathologic analysis of nine patients with CD56
      positive hematolymphoid malignancies occurring in sites other than the upper
      aerodigestive tract. The disease occurred predominantly in young and middle-aged
      men (mean age, 40 years) who often presented with swinging fever, skin rash,
      and/or hepatosplenomegaly, usually in the absence of peripheral lymphadenopathy.
      There was frequent involvement of the skin and mucosal sites, such as the
      salivary gland, lungs, and small intestine. The disease pursued a highly
      aggressive course, with most patients dying within weeks despite cytotoxic
      therapy. Although the cytologic appearances and immunophenotypic profile varied
      from case to case, the group of tumors could be unified by two morphologic
      features, namely, the presence of azurophilic granules in the cytoplasm of the
      neoplastic cells and the frequent occurrence of angiocentric and angiodestructive
      infiltrates. Since CD56 reactivity appears to confer a poor prognosis in
      hematolymphoid malignancies, we recommended inclusion of CD56 antibody in the
      routine panel for immunophenotypic analysis.

PMID- 1377164
TI  - Alpha-fetoprotein-producing acinar cell carcinoma of the pancreas.
AB  - A pancreatic carcinoma and liver metastases associated with marked elevation of
      the serum alpha-fetoprotein (AFP) level were resected from a 57-year-old man. On
      microscopic examination, the tumor cells showed a predominantly acinar
      arrangement, with tubular and trabecular structures; in some foci it had features
      of a medullary pattern. Alpha-fetoprotein, lipase, trypsin, chymotrypsin, and
      alpha 1-antitrypsin were strongly demonstrated in tumor tissue by
      immunohistochemical techniques. A biochemical analysis of AFP on affinity
      sepharose columns revealed that the AFP derived from the tumor tissues was
      similar to that of hepatocellular carcinoma. Ultrastructural study showed that
      most of the tumor cells had abundant rough endoplastic reticulum and numerous
      zymogen granules. No squamoid corpuscles, neuroendocrine granules, bile
      production, or bile canaliculi were recognized. These findings suggest that this
      unique tumor originated from acinar cells.

PMID- 1377165
TI  - Expression and chromosome localization of the murine cystic fibrosis
      transmembrane conductance regulator.
AB  - A 13.5-kb genomic fragment of the mouse cystic fibrosis transmembrane conductance
      regulator (CFTR) gene was isolated from a C57BL/6J liver DNA library, using a
      human CFTR exon 10 probe. This region of the human gene includes the most common
      cystic fibrosis mutation (deletion of the Phe508 residue) in the first nucleotide
      binding domain of CFTR. Sequence analysis demonstrated 87% identity between the
      predicted mouse and the normal human CFTR exon 10 sequences, including
      conservation of the Phe508 residue. Northern analysis revealed that the mouse
      gene is expressed in intestine, lung, stomach, kidney, and salivary gland. In
      contrast to human CFTR, murine CFTR transcripts were not detectable by Northern
      analysis in the liver or pancreas. More sensitive PCR analysis, however, revealed
      that the mouse CFTR gene is weakly expressed in other tissues, including liver
      and pancreas. During development, mouse CFTR transcripts were observed as early
      as Embryonic Day 13. Southern analysis of mouse x Chinese hamster somatic cell
      hybrid DNAs mapped the mouse CFTR locus (Cftr) to Chromosome 6 (Chr 6).
      Subsequent typing of the progeny of an interspecies backcross revealed that Cftr
      is closely linked to the proto-oncogene c-met locus (Met) in the centromeric
      region of mouse Chr 6, consistent with the observation that there is a conserved
      chromosomal segment on human chromosome 7 and mouse Chr 6.

PMID- 1377166
TI  - Regional assignment of the human keratin 5 (KRT5) gene to chromosome 12q near
      D12S14 by PCR analysis of somatic cell hybrids and multicolor in situ
      hybridization.
AB  - Keratin 5 is the major type II keratin of the basal cells of epidermis and of
      other stratified epithelia. With its type I partner, keratin 14, it constitutes a
      major fraction of the cytoskeleton of the basal cells. Because the inheritance of
      epidermolysis bullosa simplex, a disease of epidermal basal cell fragility, was
      mapped in one family to chromosome 12q close to D12S14, we undertook to localize
      the gene for keratin 5. Polymerase chain reaction analysis of somatic cell
      hybrids mapped the keratin 5 gene to chromosome 12, and multicolor fluorescence
      in situ hybridization localized it to 12q very near D12S14. This sublocalization
      exemplifies the utility of in situ physical localization in assessing the
      candidacy of genes thought to underlie inherited disorders.

PMID- 1377167
TI  - The interferon- and virus-inducible IFI-56K and IFI-54K genes are located on
      human chromosome 10 at bands q23-q24.
AB  - IFI-56K and IFI-54K are two human genes that are strongly induced by interferon
      and viruses. These genes are closely related at the protein, RNA, and promoter
      levels. By means of the somatic cell hybrid technique, the two genes have been
      previously located on chromosome 10. Using in situ hybridization, we show here
      that both IFI-54K and IFI-56K genes map to 10q23-q24. This result does not
      confirm the previous localization of the IFI-56K gene at the junction of the
      10q25 and 10q26 bands.

PMID- 1377168
TI  - Assignment of the gene coding for the alpha 2-macroglobulin receptor to mouse
      chromosome 15 and to human chromosome 12q13-q14 by isotopic and nonisotopic in
      situ hybridization.
AB  - The assignment of the gene encoding the alpha 2-macroglobulin receptor (A2MR),
      which was first described as the low-density lipoprotein receptor-related
      protein, was confirmed by nonisotopic and isotopic in situ hybridizations on
      normal human metaphases to the region 12q13-q14. The same human cDNA, which has
      95% sequence identity with the mouse A2mr, was hybridized to metaphases
      containing the Robertsonian translocation Rb(6;15)1Ald. The mouse A2mr gene was
      assigned to chromosome 15 in the region B2-D1. This locus and other loci on mouse
      chromosome 15 have been shown to be homologous with loci on human chromosome 12q.

PMID- 1377169
TI  - [A new, highly synergistic drug combination for the treatment of infections with
      multiresistant mycobacteria, especially the mycobacterium avium complex].
AB  - Rationally designed combinations of rifampicin/thiacetazone plus isoniazid and/or
      ethambutol are highly effective in the treatment of patients (including HIV-pos.)
      infected with multiply resistant mycobacteria of the M. avium complex (MAC).
      Clinical results are very promising. The high efficacy of these combinations is
      due to the synergistic potentiation of single drug activities. As soon as
      rifabutin is marketed it should replace rifampicin in the combination treatment
      of patients with highly rifampicin-resistant MAC bacteria.

PMID- 1377170
TI  - Interleukin-4 down-regulates the IL2Rp70-75 expressed on human natural killer
      cells.

PMID- 1377171
TI  - Direct demonstration of binding of aggregated mouse IgG1 to the 40-kDa Fc
      receptor for IgG (Fc gamma RII) in both high and low responders.
AB  - Several directly fluorochrome-conjugated murine monoclonal antibodies (mAb) of
      the IgG1 subclass and directed against B or T cell antigens were found to bind to
      monocytes via the 40-kDa Fc receptor for IgG (Fc gamma RII). As expected from the
      established polymorphism of Fc gamma RII, strong staining was observed in about
      75% of individuals. In the remaining 25% staining was clearly weaker, but could
      be definitely demonstrated with a mAb against the B cell-specific CD19
      differentiation antigen. Specificity of binding to Fc gamma RII was confirmed by
      the ability to block the binding of the CD19 mAb by pre-incubation with
      aggregated IgG1 or with mAb against Fc gamma RII. The extent of T cell
      proliferation induced with a CD3 mAb of the IgG1 isotype (a-Leu 4), which is
      dependent on the interaction of monocyte Fc gamma RII with the Fc portion of the
      CD3 mAb, exactly correlated with the amount of binding to Fc gamma RII in all
      individuals. Proliferation was dose-dependent for both high and low responders;
      cells of low responders did not proliferate at concentrations below 16 ng/ml of
      mAb, whereas there was a small but unequivocal proliferation at higher
      concentrations. These results confirm that monocytes from previously
      characterized "non-responders" are able to bind aggregated murine IgG1 via Fc
      gamma RII. They also demonstrate that directly labeled mAb can cause extensive
      nonspecific staining which may not be excluded by the use of control antibodies
      of the same isotype.

PMID- 1377172
TI  - A new approach to the cloning of genes encoding T-cell epitopes.
AB  - The molecular structure of antigens recognized exclusively by T cells, such as
      minor histocompatibility antigens and some antigens that provoke autoimmune
      responses, has proved difficult to determine. Recently, several antigens induced
      on tumor cells by mutagen treatment have been cloned by transfection of genomic
      DNA libraries into P1.HTR cells, screening for antigen expression using T-cell
      clones, and subsequent recovery of the integrated DNA by cosmid rescue. We have
      modified this technique and have stably transfected P1.HTR cell lines with
      polyoma T antigen, which allows episomal replication of the shuttle vector,
      pCDM8. Using pCDM8-CAT constructs, we have determined the frequency of
      transfection and plasmid copies taken up per cell under optimal transfection
      conditions. Using a pCDM8 construct which expresses the tumor-specific antigen,
      P91A (pCDM8-tum-), that is recognized by a T-cell clone, we have found that cells
      transfected with this antigen can be recognized by the T-cell clone when they are
      present at only 1%-3% of a mixed population. Progeny of a single cell transfected
      with pCDM8-tum-: pCDM8-CAT at proportions of 1:10, 1:25, and 1:50 are recognized
      by the T-cell clone. Furthermore, Hirt extracted plasmid DNA from transfectants
      expressing the tum- antigen can be amplified in bacteria, transfected back into
      P1.HTR recipients, and recognized by the T-cell clone. This approach should
      enable reasonably rapid screening of cDNA libraries for even relatively low
      abundance messages encoding, for example, minor histocompatibility and
      alloantigens, and allow their subsequent cloning.

PMID- 1377173
TI  - Genomic organization and chromosomal location of the human gene encoding the B
      lymphocyte activation antigen B7.
AB  - The human B lymphocyte activation antigen B7 provides regulatory signals for T
      lymphocytes as a consequence of binding to its ligands CD28 and CTLA-4. The cDNA
      for B7 has previously been isolated and predicted to encode a type I membrane
      protein. The predicted polypeptide has a secretory signal peptide followed by two
      contiguous Ig-like domains, a hydrophobic transmembrane region and a short
      cytoplasmic tail. Here we report the exon-intron genomic organization of human B7
      and the chromosomal location. The gene has six exons that span approximately 32
      kilobases of DNA. Exon 1 is not translated and the second exon contains the
      initiation ATG codon and encodes a predicted signal peptide. This gene structure
      is characteristic for several eukaryotic genes with tissue-specific expression.
      The third and fourth exons correspond to two Ig-like domains whereas the fifth
      and sixth exons encode respectively the trans-membrane portion and the
      cytoplasmic tail. This close relationship between exons and functional domains is
      a characteristic feature of genes of the Ig superfamily. Cell surface expression
      of the B7 gene product has previously been mapped to human chromosome 12 by
      antibody reactivity with the B7-specific monoclonal antibody BB-1. We here
      demonstrate that the B7 gene is located to the q21-qter region of chromosome 3 by
      DNA blot analysis of human x rodent somatic cell hybrids.

PMID- 1377174
TI  - Cytologic diagnosis of tuberculous lymphadenitis in children by fine needle
      aspiration.
AB  - One hundred consecutively diagnosed cases of tuberculous lymphadenitis in
      children have been analysed retrospectively. All cases were stained by May
      Grunwald Giemsa for cytomorphology and Ziehl Neelsen stain for acidfast bacilli
      (AFB). In 52 cases the material was sufficient and AFB cultures were possible. A
      diagnosis of tuberculosis was made when smears showed epithelioid cell granulomas
      or AFB on either smears or culture. M. tuberculosis and atypical mucobacteria
      were cultured in 26 and 3 cases respectively. In 6 cases the diagnosis of
      tuberculosis would have been missed but for culture studies, the cytologic smears
      were necrotic and stains for AFB negative.

PMID- 1377175
TI  - The miracles of nature is the development of a baby into an adult.

PMID- 1377176
TI  - Play therapy with young children.
AB  - This article sets out to describe and evaluate the use of Play-Therapy with young
      handicapped children. The children, mostly of pre-school age, have been seen at
      the Wolfson Centre in London, over the last five years. The work is on-going. The
      developmental programme adapted and followed, was designed at the Centre in the
      1970s, by Cooper, Moodley & Reynell. It was used to teach children with specific
      language delays. It has proved ideal to use with children with a variety of
      problems in their learning, also those with developmental delay. The
      teaching/play sessions have taken place in the children's homes and in the
      Wolfson Centre. Parental involvement has been important for success of the
      programme. Other professionals beside the teacher have been involved at the
      Centre, for monitoring the children's progress. The results shown in the annual
      reviews, or when the child attends for formal assessment, are encouraging. They
      point to the conclusion that this form of therapy can not only help the child at
      home, but also helps when he/she starts school.

PMID- 1377177
TI  - Early identification of neuro-developmental disorders.

PMID- 1377178
TI  - Development in severely visually handicapped children and visual therapy
      remediation.
AB  - The motor and cognitive development of a visually handicapped child is delayed
      due to various constraints placed on learning by the handicap. The child requires
      a functional visual assessment, and assessment of mental & motor development.
      Based on these findings a total remediation programme needs to be worked out.
      This is individualised, integrated & includes stimulation of residual vision,
      optional use of residual vision and special measures to promote general
      development.

PMID- 1377179
TI  - Amelioration of clinical severity through raised fetal hemoglobin in sickle cell
      anaemia.
AB  - In the present study, the levels of fetal hemoglobin (HbF) in sickle cell anemia
      patients were compared with sickle cell trait, beta thalassemia major and
      control. The mean HbF levels in beta thalassemia major and sickle cell anemia
      were 51.62 and 19.63% respectively. However, when the amount of HbF was expressed
      in terms of gram hemoglobin per deciliter whole blood, the mean values were 2.88
      and 1.81 respectively between the two groups, suggesting that the genetic
      mechanism controlling the different threshold levels of increased HbF in these
      disorders could probably be similar. The elevated. HbF level in sickle cell
      anemia along with moderate hematologic profile observed in the present study is
      suggested to provide amelioration of the clinical severity unlike in beta
      thalassemia major where despite raised HbF levels, the severe clinical
      implications are attributed to marked imbalance in the globin chain synthesis.

PMID- 1377180
TI  - Mapping of a visceral leishmaniasis-specific immunodominant B-cell epitope of
      Leishmania donovani Hsp70.
AB  - We have shown that a member of the 70-kDa heat shock protein (Hsp70) family is a
      major target of the humoral immune response during Leishmania donovani infection.
      A recombinant fusion protein was recognized by sera from 92% (35 of 38) of
      patients with visceral leishmaniasis, including representatives from each of the
      major regions where it is endemic. Serological analysis of recombinant Hsp70,
      expressed by a series of deletion constructs, identified the carboxy-terminal
      region as the immunodominant site. This region, which is the most evolutionarily
      divergent part of the molecule, was recognized by all sera from patients with
      visceral leishmaniasis which exhibited an anti-Hsp70 response. Purified
      recombinant L. donovani Hsp70 was not recognized by sera from patients with
      cutaneous leishmaniasis, Chagas' disease, leprosy, malaria, or schistosomiasis.
      To determine the regions involved in antibody recognition, a series of
      overlapping peptides were synthesized on polyethylene pins by the Pepscan method,
      and a hexamer, EADDRA, was identified by the visceral leishmaniasis serum samples
      as an immunodominant B-cell epitope.

PMID- 1377181
TI  - Immunological characterization of the lipooligosaccharide B band of Bordetella
      pertussis.
AB  - Two structurally and immunologically different components of Bordetella pertussis
      endotoxin can be visualized by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and silver staining: a major A band and a faster-migrating minor
      B band. Certain mutant strains of B. pertussis express only the B band, while the
      wild-type strains produce both lipooligosaccharides (LOS). Two monoclonal
      antibodies (MAbs) directed against the minor LOS B band were generated, allowing
      the study of this surface molecule on different strains of Bordetella. These two
      MAbs, designated BL-8 and BL-9, reacted strongly with phenol-water-purified LOS
      obtained from a B. pertussis LOS B mutant strain. Sodium periodate treatment of
      the purified LOS prevented binding of the MAbs, indicating the carbohydrate
      nature of the epitope(s). Western immunoblotting experiments revealed that the
      epitope(s) recognized by these MAbs is conserved on all B. pertussis and
      Bordetella bronchiseptica Vir- (avirulent) variant strains tested but is not
      present on Bordetella parapertussis and B. bronchiseptica Vir+ (virulent) wild
      type strains. Further studies showed that although present in the
      lipopolysaccharide B band expressed by Vir- strains, the epitope(s) recognized by
      the MAbs is not accessible on the surface of intact B. bronchiseptica cells. For
      B. pertussis, the density and accessibility of this epitope(s) are dependent on
      the virulence-associated or LOS phenotype expressed by the strain. Our data
      demonstrate that the expression and accessibility of the epitope(s) are
      significantly greater on the LOS B variant strains and LOS AB Vir- strains
      compared with fresh B. pertussis clinical isolates. For these latter strains,
      which are Vir+, this epitope(s) was barely detectable on the surface of intact
      bacteria, despite Western blot analyses that revealed specific reactions between
      the MAbs and the LOS B band. The two LOS B-specific MAbs had no bacteriolytic
      activity against a LOS AB wild-type strain, while the control MAb BL-2, which is
      specific for the B. pertussis LOS A band, significantly reduced the number of
      living bacteria in the same assay. Moderate lytic activity against a mutant
      strain expressing only the LOS B band was observed for MAb BL-8 but not for MAb
      BL-9 or BL-2. These data demonstrate that the type, amount, and surface exposure
      of the LOS are related to the phenotype expressed by a specific B. pertussis
      strain. In addition, the LOS B MAbs also reveal the antigenic conservation of
      carbohydrate epitopes among B. pertussis and B. bronchiseptica strains.

PMID- 1377182
TI  - Epitope mapping of hemagglutinating adhesion HA-Ag2 of Bacteroides
      (Porphyromonas) gingivalis.
AB  - Thirteen monoclonal antibodies (MAbs) directed against hemagglutinating adhesion
      HA-Ag2 of Bacteroides (Porphyromonas) gingivalis were produced by immunizing mice
      with the relevant immunoprecipitate from crossed immunoelectrophoresis (CIE).
      Crossed immuno-affinoelectrophoresis and hemagglutination experiments confirmed
      that our MAbs recognized a molecule able to bind erythrocytes and involved in the
      hemagglutination process. In immunoelectron microscopy, these MAbs labelled
      amorphous material as novel cell-bound appendages distinct from fimbriae. CIE
      experiments allowed differentiation of the MAbs according to reactivity with
      immunoprecipitates Ag2, Ag8a, and Ag8c, which define HA-Ag2. The epitopes
      recognized by nine MAbs were mapped on three main antigenic domains (I, II, and
      III) by competition experiments and further grouped according to chemical
      composition and distribution on CIE immunoprecipitate. Domain I, defined by two
      MAbs, comprises an epitope with protein and carbohydrate determinants and
      distributed on Ag2 only. Epitopes of domain IIA, defined by four MAbs, are
      distributed on Ag8a, Ag8c, and Ag2 and are essentially composed of protein
      determinants but also have carbohydrate determinants that enhance the binding of
      the MAbs but are not essential. Epitopes of domain IIB, defined by two MAbs, and
      of domain III, defined by a single MAb, have a composition similar to that of
      domain IIA epitopes but are distributed on Ag8a and Ag8c only. A competition
      enzyme-linked immunosorbent assay with serum from normal subjects and patients
      with periodontitis suggested that domain I is more immunogenic than domain II.

PMID- 1377183
TI  - Expression of Streptococcus mutans gtf genes in Streptococcus milleri.
AB  - The Streptococcus mutans glucosyltransferase (GTF) genes gtfB and gtfC were
      ligated into Escherichia coli-streptococcus shuttle plasmids and introduced into
      Streptococcus milleri. gtfB transformant KSB8 formed an S. mutans-like rough
      colony on mitis salivarius agar and expressed an extracellular GTF-I, of 158 kDa,
      and two cell-bound GTF-Is, of 158 and 135 kDa. gtfC transformant KSC43 formed a
      semirough colony on mitis salivarius agar and expressed primarily an
      extracellular GTF-SI, of 146 kDa, and two cell-bound GTF-SIs, of 146 and 152 kDa.
      The extracellular GTFs from KSB8 and KSC43 were purified and characterized. The
      two types of GTF also reacted specifically with monoclonal antibodies directed
      against each enzyme. Both enzymes synthesized significant amounts of
      oligosaccharides, consisting primarily of alpha-1,6-glucosidic linkages, as well
      as water-insoluble glucans, containing alpha-1,3-glucosidic linkages. Insoluble
      glucan-synthesizing activities of both enzymes were stimulated (three- to
      sixfold) by the addition of dextran T10 and were inhibited in the presence of 1.5
      M ammonium sulfate. The Km(s) for sucrose and the optimal pHs were also similar
      for both enzymes. However, when the transformants were grown in Todd-Hewitt broth
      supplemented with sucrose, KSC43 cells, expressing GTF-SI activity, adhered to
      glass surfaces in vitro, while KSB8 cells, expressing GTF-I activity, did not.
      These results are discussed relative to the potential role of the gtfB and gftC
      genes in S. mutans cariogenicity.

PMID- 1377186
TI  - Potentiation by novobiocin of the cytotoxic activity of etoposide (VP-16) and
      teniposide (VM-26).
AB  - The coumermycin antibiotic novobiocin, which interacts with the nuclear enzyme
      topoisomerase II, produced supra-additive toxicity to WEHI-3B D+ leukemia cells
      at clinically achievable concentrations, when combined with teniposide (VM-26) or
      etoposide (VP-16). Simultaneous exposure of cells to both agents was required for
      maximum efficacy of the combination. Novobiocin also produced supra-additive
      toxicity to A549 human lung carcinoma cells when combined with VM-26 or VP-16. At
      concentrations above the peak plasma levels achievable in patients, novobiocin
      lost its potentiating activity. Exposure of WEHI-3B D+ cells to novobiocin did
      not modify the cytotoxicity produced by the topoisomerase II inhibitor m-AMSA,
      whereas, in contrast, novobiocin antagonized the cytotoxicity of m-AMSA in A549
      cells. Although it has been suggested that inhibitors of the syntheses of DNA and
      RNA interfere with the cytotoxic activity of the epipodophyllotoxins, maximum
      potentiation of the cytotoxicities of VP-16 and VM-26 occurred at novobiocin
      concentrations that decreased the rates of synthesis of both DNA and RNA in WEHI
      3B D+ cells by about 50%. The number of DNA-topoisomerase-II covalent complexes
      stabilized by VM-26 in WEHI-3B D+ cells was greatly increased when cells were
      exposed simultaneously to VM-26 and novobiocin for 1 hr, but not when cells were
      treated with m-AMSA and novobiocin for the same period of time. Novobiocin did
      not affect the amount of covalent complexes produced by VM-26 in isolated nuclei,
      suggesting that the potentiating activity of novobiocin was not due to its direct
      interaction with the nuclear topoisomerase II enzyme. Our findings suggest that
      therapeutic levels of novobiocin may be capable of enhancing the clinical
      activities of VP-16 and VM-26.

PMID- 1377187
TI  - Insulin-like growth-factor-binding protein gene expression and protein production
      by human tumour cell lines.
AB  - The secretion of insulin-like growth-factor-binding proteins (IGFBPs) and
      expression of the genes encoding IGFBP-1, IGFBP-2 and IGFBP-3 have been studied
      in a panel of cell lines derived from breast carcinomas, Wilms' tumour,
      neuroblastoma, retinoblastoma, colon carcinoma, liver adenocarcinoma, Burkitt's
      lymphoma and a non-small-cell lung carcinoma. All cell lines, with the exception
      of the Burkitt's lymphoma cell line, secreted IGFBPs, as detected by affinity
      labelling. A 34-kDa BP was present in the conditioned media of all IGFBP
      secreting cell lines, whereas BPs ranging from 18 kDa to 53 kDa were variably
      secreted. All IGFBP-secreting cell lines expressed the IGFBP-2 gene as determined
      by Northern blot analysis. The Wilms' tumour, the neuroblastoma and the
      retinoblastoma cell line expressed the IGFBP-2 gene only. All other cell lines,
      with the exception of the Burkitt's lymphoma, expressed the IGFBP-2 gene and, in
      addition, either the IGFBP-1 gene and/or the IGFBP-3 gene. IGFBP-1 gene
      expression could be detected by reverse transcriptase polymerase chain reaction
      only. IGFBP-3 gene expression was detected by Northern blot analysis, but
      transcripts were less abundant than IGFBP-2 mRNAs. These findings indicate that
      the expression of multiple BP genes and the secretion of BPs may be a common
      property of tumour cells.

PMID- 1377184
TI  - Inhibition of adhesion of S-fimbriated Escherichia coli to buccal epithelial
      cells by human milk fat globule membrane components: a novel aspect of the
      protective function of mucins in the nonimmunoglobulin fraction.
AB  - We investigated the presence of factors in human milk that inhibit invasion of
      pathogenic bacteria. The effect of human milk fat globule membrane (HMFGM)
      components on adhesion of cloned S-fimbriated Escherichia coli to human buccal
      epithelial cells was analyzed. S fimbriae are a common feature of E. coli strains
      causing sepsis and meningitis in newborns and are bound to epithelia via sialyl
      (alpha-2-3)galactoside structures. Human milk fat globules (HMFG) could be
      agglutinated by the above-mentioned bacteria. Agglutination could be inhibited by
      fetuin, human glycophorin, and alpha 1-acid glycoprotein. In addition,
      pretreatment of HMFG with Vibrio cholerae neuraminidase markedly reduced
      bacterium-induced agglutinations, indicating the involvement of neuraminic acid
      containing glycoproteins. In contrast, lipid droplets of infant formula or
      artificial lipid emulsions (Intralipid) could not be agglutinated. HMFG were
      present in stools of breast-fed neonates as shown by indirect immunofluorescence
      staining with a monoclonal antibody directed against carbohydrate residues
      present on HMFGM. These HMFG could be agglutinated by bacteria. HMFG inhibited E.
      coli adhesion to buccal epithelial cells. To further characterize relevant E.
      coli binding structures, HMFGM components were separated by gel chromatography.
      The mucin fraction showed the most pronounced inhibitory effect on adhesion of S
      fimbriated E. coli to human buccal epithelial cells. Our data suggest that HMFG
      inhibit bacterial adhesion in the entire intestine and thereby may provide
      protection against bacterial infection.

PMID- 1377188
TI  - Capillary occlusion and secondary angiogenesis: case report.
AB  - The first follow-up control 5 days later (14.1.1990) showed a fresh capillary
      occlusion with massive red blood cell diapedesis. The arteriolar limb of the
      capillary is filled with erythrocytes up to the occlusion. Since capillary
      occlusion probably allowed some plasma flow at first, blood cells distal to the
      occlusion were washed away. After 53 days (8.3.1990) extravasal cells could no
      longer be made out. At the upper margin of the image a newly formed capillary
      loop can be seen. The channel of the old capillary seemed to have disappeared.
      Seventy-three days after occlusion, on 28th of March, the tip of the capillary,
      already demonstrated on 8th of March, had further grown distally. The capillary
      had crossed the neighbouring diagonal capillary. Twelve days later (9.4.1990) a
      remarkable growth connected with formation of a collateral was observed. The new
      capillary grew in direction of the former capillary channel. On 22nd of April the
      new capillary had almost got back to its old form. The collateral vessel formed
      on 9th of April had also grown and could be well distinguished. The different
      branches were immediately well perfused (mean erythrocyte velocity is v = 0.74
      mm/s). The capillary were growing at different speeds. The new capillary had
      visibly grown by 220 microns over a period of 47 days which corresponds to an
      average growth of 4.7 microns a day. The capillary was growing fastest between
      the 9th and 22nd of April. A minimum of growth of 2 microns was observed within
      the first 11 days of the observation period.

PMID- 1377185
TI  - Effects of staphylococcal enterotoxin B on rodent mast cells.
AB  - Staphylococcal enterotoxin B (SEB) was tested in rodent mast cell cultures for
      the release of serotonin. Both rat RBL-2H3 mast cells and murine peritoneal cells
      released serotonin after SEB stimulation in culture. Release of serotonin in RBL
      2H3 cells depended on the concentration of SEB; an appreciable release was seen
      at 50 micrograms/ml. The release of serotonin was not due to cell death.
      Serotonin release could be enhanced by bradykinin but not by vasoactive
      intestinal peptide, substance P, lipopolysaccharide from Salmonella typhimurium,
      the calcium ionophore A23187, acetylcholine, adenosine, 5-hydroxyeicosatetraenoic
      acid, indomethacin, or phorbol myristate acetate. SEB bound directly to the
      membrane of RBL-2H3 mast cells, and the SEB-binding site, the presumptive
      receptor, appeared to be a protein. The SEB receptor could not be capped under
      membrane-capping conditions, and serotonin release could not be enhanced by
      attempts to cross-link the receptor. These results suggest that mast cells may be
      an important cell type involved in SEB toxicosis and that release of serotonin
      may be enhanced by activation of the kinin-kallikrein system.

PMID- 1377189
TI  - Macromolecular transport across endothelial monolayers.
AB  - We studied the macromolecular size-selective transport characteristics of
      polycarbonate (PC) filters with defined pore radius (rp; 15,000 to 400 A) as well
      as 2,000 A rp PC filter-bovine pulmonary artery endothelial cell (EC) monolayer
      sandwich under zero hydrostatic pressure conditions using fluorescein
      isothiocyanate-hydroxyethyl starch (FITC-HES, 16 A less than ae less than 100 A),
      and 2-methoxy-2,4-diphenyl-3(2H) furanone-bovine serum albumin (MDPF-BSA, ae =
      35.5 A). We surprised to find substantial convective solute transport (solute
      drag) across the filter-endothelial sandwich. This effect was increased by large
      rp (15,000 A) filters and prevented by 400 A rp filters. Positive hydrostatic
      pressure across 2,000 A rp filters increased convective solute transport and
      negative pressure prevented this effect. High, medium and low permeability
      monolayers on 2,000 A filters progressively attenuated the solute drag effect
      seen across these filters without cells. The decline in monolayer permeability
      was associated with an increased filter area covered by cells; approximately 50
      and 95% as well as greater than 99%, respectively. Although significant
      restricted diffusion was seen across low permeability monolayers, this pattern
      was distinct from that measured in single frog capillaries. Restricted diffusion
      by low permeability monolayers under conditions that produce solute drag document
      the significant barrier effects of high confluence endothelial monolayers, in
      vitro. These data show that solute transport across endothelial monolayers is due
      to diffusion+convective solute drag. The degree of the solute drag effect across
      the filter-endothelial sandwich is a direct function of monolayer confluence.

PMID- 1377190
TI  - [Nevus spongiosus et albus mucosae].
AB  - An 8-year-old girl with a non-familial case of white sponge nevus (WSN) is
      presented. The differential diagnosis is discussed with reference to anamnestic,
      clinical and histopathological data. In keratin expression, WSN resembles the
      epithelia of the hard palate and the tongue.

PMID- 1377191
TI  - [Immunohistologic characterization of skin metastases in a patient with
      simultaneous cancers of the rectum and cervix].
AB  - A patient with skin metastases several years after surgical treatment of
      carcinoma of the cervix and the rectum is presented. Comparative histology and
      immunohistochemical analysis with anti-cytokeratin antibodies implicated the
      carcinoma of the cervix as the source of the skin infiltrates. Based on this
      patient's case record, the use of anti-cytokeratin antibodies for identification
      and subtyping of epithelial or carcinoma cells is discussed with special
      reference to cytokeratin 7.

PMID- 1377192
TI  - Effect of osteopathic medical management on neurologic development in children.
AB  - For 3 years, children between 18 months and 12 years of age with and without
      recognized neurologic deficits were studied at the Osteopathic Center for
      Children. Their response to 6 to 12 osteopathic manipulative treatments directed
      to all areas of impaired inherent physiologic motion was estimated from changes
      in three sensory and three motor areas of performance. Houle's Profile of
      Development was used to compare neurologic with chronologic age and rate of
      development, and scores were age-adjusted. Results in children after treatment
      were compared with those following a waiting period without treatment. Neurologic
      performance significantly improved after treatment in children with diagnosed
      neurologic problems and to a lesser degree in children with medical or structural
      diagnoses. The advances in neurologic development continued over a several
      months' interval. The results support the use of osteopathic manipulative
      treatment as part of pediatric healthcare based on osteopathic medical philosophy
      and principles.

PMID- 1377193
TI  - DNA ligands as radiomodifiers: studies with minor-groove binding
      bibenzimidazoles.
AB  - An iodinated bibenzimidazole, iodoHoechst 33258, was previously reported to
      markedly sensitize DNA and cells to UV-A, exemplifying the potential of iodinated
      DNA ligands as radiosensitizers, a rational extension of sensitization by
      halogenated pyrimidines. However, unlike the latter sensitizers, iodoHoechst
      33258 is not a sensitizer of ionizing radiation, presumably due to the innate
      radioprotective properties of the uniodinated ligand. Experiments with purified
      DNA show that both Hoechst 33258 and Hoechst 33342 decrease the yield the
      radiation-induced DNA strand breakage. The ligands bind at discrete sites in the
      minor groove of DNA, and analysis on DNA sequencing gels show pronounced
      protection at the ligand binding sites, as well as more generalized protection.
      The extent of protection of strand breakage on plasmid DNA and the fact that it
      persists in the presence of 0.5 M NaCl (which prevents low affinity ionic binding
      between the high affinity sites) suggests that the protective effects of bound
      ligand are not confined to the high affinity binding sites in the minor groove.
      The mechanisms of this generalized protection is unknown, but there is some
      evidence indicating that the H-atom donation from the ligand may account for the
      site-specific protection. The extent of protection is much diminished, but still
      evident, in the presence of 100 mM mannitol, a known hydroxyl radical scavenger,
      indicating that some of the protective effects might relate to DNA damage
      mediated by direct action. Further evaluation of the mechanisms of protection
      should enable development of both more active radioprotectors and, by elimination
      of the radioprotective features from halogenated DNA ligands, more effective
      radiosensitizers.

PMID- 1377194
TI  - Treatment of myelodysplastic syndromes with hematopoietic growth factors.
AB  - Clinical trials with hematopoietic growth factors (granulocyte-macrophage colony
      stimulating factor [GM-CSF], granulocyte colony-stimulating factor [G-CSF],
      interleukin-3, or erythropoietin) have been performed on patients with
      myelodysplastic syndromes. Absolute neutrophil counts can be readily raised to
      within the normal range by treatment with GM-CSF or G-CSF. Increases in platelets
      and hemoglobin have been reported after treatment with interleukin-3 and
      erythropoietin, respectively. Cytogenetic and molecular genetic analyses have
      demonstrated that both normal and malignant precursor cells are stimulated by
      cytokine therapy.

PMID- 1377195
TI  - Differentiation therapy.
AB  - A variety of compounds are able to induce myeloid leukemia cells to differentiate
      into morphologically and functionally mature cells. Vitamin D derivatives,
      retinoids, interferons, and polar-planar compounds are agents that demonstrate
      such activity in vitro and have been employed as therapy for the myelodysplastic
      syndromes.

PMID- 1377196
TI  - Thin-layer electrophoresis of hydroxyethyl starches on a modified silica gel
      support.
AB  - The recent developed thin-layer electrophoresis on modified silanized silica gel
      was applied to the separation of hydroxyethyl starches (HES) and glycogen and of
      HES with different degrees of substitution. This method permits a rapid
      qualitative and semi-quantitative determination of HES in animal tissues such as
      liver, lung, heart and kidney after their disintegration with alkali and
      precipitation with ethanol.

PMID- 1377197
TI  - Bayley's infant behavior record ratings of infants with recurrent apnea:
      behavioral profile and correlates with apnea, age, and developmental status.
AB  - The goal of this study was to provide a behavioral profile of apneic infants and
      to examine relationships between behavioral ratings, apnea frequency, age, and
      concurrent developmental status. Two samples of previously apneic infants were
      included in this exploratory analysis using the Infant Behavior Record (IBR) as a
      measure of temperament. Frequency of IBR suspect ratings was more than twice
      those reported for the Bayley standardization sample for tension, object
      orientation, attention, and reactivity. Apnea frequency, age, and developmental
      status were significantly related to a number of IBR ratings with relationships
      remaining significant for apnea and decreased responsiveness to persons and
      sensory interest after controlling for age and developmental status in the
      combined samples. These findings are consistent with a behavioral profile
      described as a lethargic temperament but may reflect early physiologic
      instability rather than inherent behavioral style.

PMID- 1377198
TI  - Comparing the effects of neonatal intensive care unit intervention on premature
      infants at different weights.
AB  - This study investigated the efficacy of an intervention program in the neonatal
      intensive care unit (NICU) on the development of premature infants from low
      socioeconomic status (SES) backgrounds. Sixty premature infants born at a county
      hospital over an 8-month period and their mothers were the focus of this study.
      The infants were assigned to either a control group or an experimental group. The
      experimental group received teaching and reinforcement about their babies'
      behavior from a child development specialist when they visited the NICU. Of the
      initial 60 infants, 49 completed the study at 8 months, but because data from
      only the first born of twin pairs were used, 41 infants were included in the
      final analysis. Infants were divided into two weight groups: one below and one
      above 1500 g. There was a significant effect of the intervention on the infants'
      mental and motor scores at 4 and 8 months. Significant differences on the total
      Home Observation for Measurement of the Environment (HOME) were noted between the
      groups. There were some significant differences between intervention and control
      groups on the interaction of the mother with the infant at 4 months but not in
      the play situation at 8 months. The lighter premature infants had a greater boost
      from the intervention than did the heavier premature infants. The intervention
      had no effect on the mother's perception of her infant's temperament or on her
      confidence skills. In line with other research findings, the infants who weighed
      less than 1500 g seemed to have benefited most from the intervention, and the
      effect of the intervention was most notable at 4 months.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1377199
TI  - The relationship between environmental risk and developmental outcome.

PMID- 1377200
TI  - Parvalbumin and calbindin immunocytochemistry reveal functionally distinct cell
      groups and vibrissa-related patterns in the trigeminal brainstem complex of the
      adult rat.
AB  - Immunocytochemistry for calbindin (CA) and parvalbumin (PA) was combined with
      retrograde tracing from the thalamus, superior colliculus (SC), and cerebellum to
      define the ascending projections of neurons in the rat's trigeminal (V) brainstem
      complex that express immunoreactivity for these calcium binding proteins. Many PA
      immunoreactive neurons were observed in trigeminal nucleus principalis (PrV).
      Many of these cells projected to thalamus and a few sent axons to SC. In ventral
      PrV, PA-immunoreactive neurons were arranged in a vibrissa-related pattern. A
      very small number of large CA-immunoreactive neurons were observed in dorsomedial
      PrV. None of these cells were labeled by our tracer deposits. Small neurons in V
      subnucleus oralis (SpO) were also immunoreactive for PA, but none were
      retrogradely labeled. A small percentage of the large neurons in SpO were CA
      immunoreactive; many of these were retrogradely labeled by tracer injections in
      the thalamus and/or SC. In V subnucleus interpolaris (SpI), many small to medium
      sized cells were PA-positive and they were arrayed in a vibrissae-like pattern.
      None of these neurons were retrogradely labeled from any of the above-listed
      targets, but many were retrogradely labeled by tracer injections into ipsilateral
      PrV. SpI also contained many large CA-immunoreactive cells. Many of these
      projected to the thalamus and/or SC and some were also retrogradely labeled by
      tracer injections into ipsilateral PrV. In V subnucleus caudalis (SpC), very dark
      PA-immunoreactive neurons were located in the inner part of lamina II and less
      often in laminae I. Lightly labeled cells were located in the magnocellular
      laminae and formed vibrissa-related aggregates. None of these neurons were
      retrogradely labeled by our tracer injections. CA-immunoreactive cells were
      located throughout the depth of lamina II in SpC and smaller numbers were also
      visible in lamina I and layers III-V. A small percentage of the CA-positive cells
      in lamina I and in the magnocellular layers were retrogradely labeled from the
      thalamus. These data indicate that PA and CA antisera identify two cell
      populations in whisker-related regions of the V brainstem complex and that PA
      cells are somatotopically patterned in PrV, SpI, and SpC. These markers also
      distinguish two cell groups in superficial laminae of the medullary dorsal horn.

PMID- 1377201
TI  - Changes of chemoarchitectural organization of the rat spinal cord following
      ventral and dorsal root transection.
AB  - Time-related changes in the distribution of chemical messengers in the rat spinal
      cord following the transection of dorsal and ventral roots were observed by using
      immunohistochemistry for the following antigens: microtubule-associated protein 2
      (MAP2), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (Gal),
      Met-enkephalin (Enk), neuropeptide Y (NPY), and serotonin (5-HT). To investigate
      dendrocytoarchitectonic organizational changes, morphometric analyses were
      performed on both the gray and the white matter of tissue samples stained with
      MAP2 antiserum. A significant reduction in the area of gray matter on the
      lesioned side was seen from 1 to 24 weeks postoperation, and progressive changes
      in the shape of the gray matter were also observed. CGRP-immunoreactive fibers
      were reduced in number in the posterior horn after root transection, except in
      the lateral part of lamina I. In contrast, CGRP immunoreactivity in the anterior
      horn cells of the ipsilateral side was increased early after transection, but
      later it progressively decreased. Root transection also caused significant
      reduction in the number of SP-immunoreactive fibers in the posterior horn, but no
      changes were seen in the anterior horn. Gal immunoreactivity was also affected by
      root transection, and it changed in a similar way to CGRP immunoreactivity. 5-HT
      immunoreactive fibers were increased in the posterior horn after transection, and
      later decreased. In the anterior horn, there were no changes in the intensity or
      distribution pattern of 5-HT-immunoreactive nerve fibers following root
      transection. Enk and NPY immunoreactivity in the anterior and posterior horns was
      not affected by root transection up to 24 weeks postoperative. These results show
      that spinal root transection caused significant changes in the chemoarchitectural
      organization of nerve fibers containing certain types of chemical messengers,
      such as CGRP, SP, Gal, and 5-HT, in addition to altering dendritic geometry in
      the spinal cord.

PMID- 1377202
TI  - Immunoreactivity to GABAA receptor in the outer plexiform layer of the cat
      retina.
AB  - The distribution of GABAA receptor in the outer plexiform layer of cat retina was
      studied by immunocytochemistry with monoclonal antibodies. Staining was observed
      at the base of the cone pedicle, extracellularly, in association with the "triad"
      synaptic complex. Some bipolar dendrites and the basal processes that
      interconnect the cone pedicles were also stained. Rod spherules and horizontal
      cells were negative. The findings support the idea that the cone horizontal cells
      are GABAergic.

PMID- 1377203
TI  - The tectorecipient zone in the inferior olivary nucleus in the rat.
AB  - Tecto-olivary and olivocerebellar projections in the rat were investigated in
      order to identify the tectorecipient zone in the inferior olivary nucleus and to
      determine whether inferior olivary neurons projecting to the cerebellar tecto
      olivo-recipient zones (lobule VII, crus II, lobulus simplex, and paramedian
      lobule) originate in the different regions within the tectorecipient zone. An
      electrophysiological method and an axonal transport technique of wheat-germ
      agglutinin-conjugated horseradish peroxidase were used. The tectorecipient zone
      was identified in the caudomedial region of the medial accessory olive. Neurons
      projecting to lobule VII originated in the caudomedial region of the
      tectorecipient zone, but those to crus II, lobulus simplex, and paramedian lobule
      originated in its rostrolateral region. These observations suggest that there are
      two independent tecto-olivo-cerebellar systems: 1) superior colliculus--the
      medial region of the tectorecipient zone--lobule VII--the caudomedial region of
      the fastigial nucleus; and 2) superior colliculus--the rostralateral region of
      the tectorecipient region--crus II, lobulus simplex, and paramedian lobule--the
      dorsolateral protuberance of the fastigial nucleus.

PMID- 1377204
TI  - Two types of motoneurons supplying dorsal fin muscles in lamprey and their
      activity during fictive locomotion.
AB  - The location and dendritic morphology of motoneurons supplying the dorsal fin
      muscles were studied in the lamprey spinal cord (Ichthyomyzon unicuspis).
      Motoneurons were retrogradely labelled after injection of HRP into the fin
      muscles or after its application on the cut ends of the ventral roots. HRP
      labelled cells were subsequently reconstructed, in the horizontal and/or
      transverse planes. Fin motoneurons were also injected intracellularly with
      Lucifer Yellow and their detailed three-dimensional structure was analysed by
      confocal laser-scanning microscopy. Unlike myotomal motoneurons, which are
      closely spaced in the lateral cell column, fin motoneurons were distributed along
      the spinal cord separately or in pairs. They could be distinguished from
      motoneurons supplying trunk muscles by having a limited number of dendrites in
      the lateral part of the spinal cord. In addition, some fin motoneurons extend
      their dendrites into the dorsal column. The motor cells innervating fin muscles
      were divided into two types based on their dendritic morphology. Type I have a
      widespread dendritic tree in the rostrocaudal direction and, with few exceptions,
      completely restricted to the ipsilateral side. A proportion (25%) of these cells
      have dendrites extending into the dorsal column. Type II fin motoneurons extended
      their dendrites both ipsi- and contra-laterally. The contra-lateral dendrites
      pass below and above the central canal. The dendrites send off branches into the
      dorsal columns on both the ipsi- and the contra-lateral sides. Electron
      microscopic analysis showed that both type I and type II fin motoneurons receive
      numerous synaptic contacts from dorsal column axons. During fictive locomotion
      both types of motoneurons are active in antiphase in relation to myotomal
      motoneurons and to the main locomotor burst.

PMID- 1377205
TI  - Callosal and superior temporal sulcus contributions to receptive field properties
      in the macaque monkey's nucleus of the optic tract and dorsal terminal nucleus of
      the accessory optic tract.
AB  - To assess the functional contribution of the cortical input to the receptive
      field properties of nucleus of the optic tract (NOT) and dorsal terminal nucleus
      (DTN) neurons, a first set of experiments evaluated the response properties of
      NOT-DTN cells in monkeys with split corpus callosum. With respect to visual
      latency, direction specificity, directional tuning width, velocity tuning, ocular
      dominance, and binocular interaction, they were indistinguishable from NOT-DTN
      neurons in normal monkeys. However, a clear difference was found regarding the
      extent of the receptive fields. Whereas, in normal monkeys, NOT-DTN receptive
      fields include the contralateral hemifield and the fovea as well as substantial
      parts of the ipsilateral visual field, receptive fields in callosum-split monkeys
      stop abruptly at, or close to, the vertical 0-meridian and do not extend into the
      ipsilateral visual field. In addition, the location of the highest sensitivity
      within the receptive fields in callosum-split monkeys is shifted away from the
      vertical 0-meridian in comparison to normal animals. In a second set of
      experiments, we antidromically identified cortical neurons within the superior
      temporal sulcus that project to the NOT-DTN. These neurons were found in area MT
      mostly near the border of MTp or MSTl. All of them are direction selective for
      ipsiversive stimulus movement, and their receptive fields extend substantially
      into the ipsilateral visual hemifield. Neurons with other preferred directions
      did not project to the NOT-DTN. These results contribute to the explanation of
      the ipsiversive directional deficits in slow eye movements after cortical
      lesions, as well as the asymmetries in optokinetic nystagmus with hemifield
      stimulation after transection of the corpus callosum. The more general
      implication of the results is that a particular function of a cortical area can
      only be understood by knowing its subcortical connections.

PMID- 1377206
TI  - Anatomy and fine structure of neurons in the deutocerebral projection pathway of
      the crayfish olfactory system.
AB  - Golgi impregnation and neurobiotin injection were used to examine details of the
      neural pathways in the olfactory system of the freshwater crayfish, Procambarus
      clarkii. Deutocerebral projection neurons (globuli cells) were directly injected
      with neurobiotin. These neurons have dendritic arborizations in the ipsilateral
      olfactory and accessory lobes, and they project axons to the lateral
      protocerebrum, where they terminate in microglomeruli of the hemi-ellipsoid body.
      The axons of the deutocerebral projection neurons are readily impregnated by
      Golgi procedures, and they terminate as an expanded membranous knot about 5
      microns in diameter. Electron microscopy on Golgi-stained terminals has revealed
      that each knot makes several hundred synapses with small spine-like or shaft-like
      processes of postsynaptic neurons. Injection of neurobiotin into local
      interneurons of the hemi-ellipsoid body and subsequent examination of stained
      preparations with the electron microscope reveals that these cells are a major
      postsynaptic target of the deutocerebral projection neurons. Furthermore, the
      local interneurons make extensive efferent synaptic connections with unidentified
      neurons in the terminal medulla.

PMID- 1377207
TI  - Eccrine syringofibroadenomatosis: a clinical and histologic study and review of
      the literature.
AB  - A 56-year-old man had an 11-year history of a psoriasiform eruption of the palms,
      soles, and shins. An examination revealed well-demarcated patches and plaques of
      erythematous, fissured, and hyperkeratotic skin with focal erosions. There was no
      clinical evidence of ectodermal dysplasia. On histologic examination these
      lesions proved to be eccrine hamartomas that consisted of anastomosing cords and
      strands of cuboidal epithelial cells with well-formed ducts and a fibrovascular
      mucinous stroma. Eccrine ductal origin was indicated by histopathologic,
      histochemical, immunopathologic, and electron microscopic evaluation. These
      multiple palmoplantar eccrine hamartomas, unassociated with ectodermal dysplasia,
      represent a sporadic hamartomatous condition that is best designated as "eccrine
      syringofibroadenomatosis."

PMID- 1377208
TI  - Multiple linear cylindromas.
AB  - We report a case of multiple cylindromas with a linear arrangement on the lower
      right extremity. The patient had more than 100 tumors, but the scalp was spared.
      Some tumors showed overlapping features with eccrine spiradenoma. We believe this
      is the first report of multiple linear cylindromas.

PMID- 1377209
TI  - Generalized papular xanthomatosis in mycosis fungoides.
AB  - Xanthomas can occur in association with underlying lymphoproliferative disease,
      or they can result from lipid deposition in damaged or altered skin. We report a
      case of generalized papular xanthomas that developed in a patient with Sezary
      syndrome. The xanthomas were composed of foamy histiocytes that were shown by
      immunoperoxidase staining to be of the monocyte/macrophage lineage. Electron
      microscopic studies revealed lipid vacuoles, lysosomes, and myelin figures but no
      Birbeck granules, features that are consistent with a non-X histiocytosis.
      Generalized papular xanthomatosis has not been previously described in a patient
      with cutaneous T-cell lymphoma.

PMID- 1377211
TI  - The effect of short-term fasting and a single meal on protein synthesis and
      oxygen consumption in cod, Gadus morhua.
AB  - Rates of protein synthesis and oxygen consumption (MO2) in cod were compared in
      both fasted and refed animals. During a 14-day fast both protein synthesis and
      respiration rates fell to stable values after 6 days. When a meal of whole
      sandeel at 6% body weight was fed to fish fasted for 6 days, protein synthesis
      and MO2 increased to a maximum at between 12 and 18 h after feeding. Peak MO2 was
      about twice the pre-feeding values, while whole animal protein synthesis
      increased four-fold. There were differences between tissues in the timing of
      maximum protein synthesis; the liver and stomach responded faster than the
      remainder of the body. Maximum protein synthesis rates in the liver and stomach
      occurred at 6 h after feeding, at which time their calculated contribution to
      total MO2 was 11%. Similar calculations suggested that the integrated increment
      in whole animal protein synthesis contributed between 23% and 44% of the post
      prandial increase in MO2. It was concluded that protein synthesis is an important
      contributor to increased MO2 after feeding in cod.

PMID- 1377210
TI  - Correlations of unique clinical, immunotypic, and histologic findings in
      cutaneous gamma/delta T-cell lymphoma.
AB  - Cutaneous T-cell lymphoma is a malignancy of T cells that express a clone
      specific heterodimer T-cell receptor for antigen. The second recognized case of
      an epidermotropic malignancy of T-cells expressing gamma/delta T-cell receptor
      expressing cells is reported. The immunophenotype of the malignant T-cells was
      CD3+, CD2+, CD7+, gamma/delta T-cell receptor+, CD4-, CD8-, and alpha/beta T-cell
      receptor-. The clinical features were remarkable for extreme epidermotropism with
      a scant dermal lymphomatous infiltrate. Profound keratinocyte necrosis occurred
      in areas of malignant skin infiltrates. Despite cutaneous lesions covering more
      than 50% of the skin surface of the patient, no adenopathy or splenomegaly was
      detected. The intense epidermotropism of this patient's gamma/delta T-cell
      receptor-expressing cells and the putative cytolytic properties of CD4- CD8-
      gamma/delta contributed to the destruction of epidermis. Remission was induced
      with a combination of electron beam and extracorporeal photochemotherapy.

PMID- 1377212
TI  - The effects of decentralization on substance P-immunoreactivity in the anterior
      major pelvic ganglion of the male guinea pig.
AB  - The anterior major pelvic ganglion (AMPG) of the male guinea pig possesses a
      substance P (SP)-immunoreactive peri-neuronal plexus. Selective nerve
      transections involving the principal inputs of the AMPG, the hypogastric and
      pelvic nerves, indicate that the SP-immunoreactive peri-neuronal plexus is
      derived from multiple sources: an extrinsic source involving both the hypogastric
      and pelvic nerves, and another source (possibly the projections of small
      intensely fluorescent cells). SP-immunoreactivity (IR) is not normally present in
      the neuronal perikarya of the AMPG. Evidence is presented that suggests the
      absence of SP-IR is due to an active suppression of SP-synthesis. This seems to
      be achieved by a trans-synaptic mechanism involving the hypogastric nerve which,
      after transection, leads to the appearance of neuronal perikarya exhibiting SP-IR
      (less than 1% of the total neuronal population of the AMPG). Up to 65% of the
      neuronal perikarya of the AMPG have the ability to synthesize SP, as demonstrated
      by SP-IR after 24 h in vitro. A more potent factor in the down-regulation of SP
      synthesis seems to be exerted by the pelvic genito-urinary organs, especially the
      prostate.

PMID- 1377213
TI  - Modern histochemical methods using enzymes as markers.
AB  - In the 25 years since the idea that histochemically detectable enzymes could
      serve as a marker of ligands, the world of histochemistry has undergone a
      dramatic change. Today slides of immunostained tissue sections may be filed
      together with hematoxylin- and eosin-stained slides and may be examined at one's
      leisure. Antigens are now localized at the ultrastructural level as well as at
      the light microscopic level permitting one to wonder about the intricacies and
      beauties of living creatures. Genes which mandate our body since the day of
      conception to the day of death can now easily be probed with enzyme markers. Even
      with all these success stories, some dreams which I had hoped to accomplish with
      the method are not yet realized. Unlike the chemical and physical properties of
      inert objects, living organisms are provided with a fixed genetic program. By
      recognizing the point in the program which is being executed, one can deduce the
      potential FUTURE activities of the cells and tissues. I hypothesize that this is
      not an impossible task since (1) histochemistry and immunohistochemistry already
      provide us information on the PAST activities of cells and tissues, (2) in situ
      hybridization describes PRESENT gene activities, and (3) newer methods allow for
      the determination of potential gene function. Thus it is possible to peek at the
      future.

PMID- 1377214
TI  - New immunoenzyme-cytochemical stainings for the in situ detection of epitope
      specificity and isotype of antibody forming B cells in experimental and natural
      (auto) immune responses in animals and man.

PMID- 1377215
TI  - Molecular anatomy of an autoantigen: T and B epitopes on the nicotinic
      acetylcholine receptor in myasthenia gravis.

PMID- 1377216
TI  - Neutralization of the anticoagulant effects of glycosaminoglycans by serum
      amyloid P component: comparison with other plasma and platelet proteins.
AB  - Serum amyloid P protein (SAP) is a heparin-binding protein that is found in blood
      and connective tissues including some types of vascular basement membrane. In
      this article we present evidence that SAP is capable of blocking the
      anticoagulant effects of glycosaminoglycans. SAP neutralized the catalytic effect
      of heparin on the thrombin-antithrombin III reaction more effectively than
      vitronectin, histidine-rich glycoprotein, fibronectin, and high-molecular-weight
      kininogen and almost as effectively as platelet factor 4. SAP also blocked the
      effects of heparin and dermatan sulfate on the inhibition of thrombin by heparin
      cofactor II. We found evidence for the formation of a high-affinity 1:1 complex
      between SAP and heparin and for inhibition of binding of both thrombin and
      antithrombin III to heparin-Sepharose by SAP. We conclude that SAP may account
      for much of the heparin-neutralizing capacity of plasma under some conditions and
      that basement-membrane-bound SAP may modulate extravascular coagulation by
      blocking the anticoagulant effects of basement membrane glycosaminoglycans.

PMID- 1377217
TI  - Coordinated appearance of beta 1 integrins and fibronectin during corneal wound
      healing.
AB  - Fibronectin, which appears at wound sites, serves as a temporary matrix for the
      epithelial migration involved in healing. Cellular responses to fibronectin have
      not yet been elucidated. We visualized beta 1 integrins, fibronectin, laminin,
      and collagen type IV by immunofluorescence techniques at various intervals after
      single, nonpenetrating incision in the corneas of rats to investigate the
      chronologic changes in the localization of these proteins during corneal
      epithelial wound healing. In unwounded corneas beta 1 integrins were found on
      basal cells of the corneal epithelium and fibronectin was found in the corneal
      subepithelial region, at Descemet's membrane, and in streaks between collagen
      fibers of the stroma. Both laminin and collagen type IV were found in the
      subepithelial region and Descemet's membrane. Immediately after the incision,
      fibronectin was visible on the surface of the V-shaped defect of the stroma;
      epithelial cell expressed beta 1 integrins began to migrate over the defect and
      to fill it. When healing was almost completed, beta 1 integrin staining of
      epithelial cells diminished, except for in basal cells. Staining of fibronectin
      diminished at the interface between the new epithelium and the stroma. Laminin
      and collagen type IV were not seen between the migrating epithelial cells and the
      underlying stroma until epithelial cells completely covered the defect.
      Appearance and disappearance of beta 1 integrins and fibronectin are thus well
      coordinated during corneal epithelial wound healing process, suggesting an active
      involvement of beta 1 integrins and fibronectin.

PMID- 1377218
TI  - Short amino acid sequences derived from C1q receptor (C1q-R) show homology with
      the alpha chains of fibronectin and vitronectin receptors and collagen type IV.
AB  - The human C1q receptor (C1q-R) is a 65-70-kd, highly acidic, hydrophobic
      glycoprotein that is expressed on a wide variety of cell surfaces. Although the
      C1q-R itself appears to bind preferentially to C1q, the region of the ligand to
      which C1q-R binds is the primary binding site for several other molecules,
      including fibronectin, laminin, and C1q inhibitor (chondroitin 4-sulfate
      proteoglycan) as well as the complement C1r2C1s2 tetramer. In order to further
      characterize the C1q-R molecule with regard to its structure and function, highly
      purified C1q-R was obtained from Raji cells using DEAE-Sephacel and C1q-Sepharose
      CL-4B chromatography. Studies performed with 125I-labeled C1q-R demonstrated that
      whereas the C1q-R molecule binds poorly to a variety of human collagens including
      types II, III, and V, markedly enhanced binding is observed with type IV collagen
      and moderately enhanced binding with type I collagen. Amino acid composition
      studies show that the C1q-R molecule contains approximately 44% hydrophobic and
      12.6% hydrophilic residues with a ratio of negatively charged to positively
      charged residues of about 2:1. Treatment of 125I-labeled C1q-R with
      endoglycosidase F lowers the apparent molecular size from 70 to 58 kd, whereas
      endoglycosidase H lowered the size to 64 kd. Treatment with neuraminidase, on the
      other hand, shifted the size of C1q-R to 60 kd. These results suggest the
      presence of several highly sialylated complex-type or high mannose-type N-linked
      oligosaccharide side chains. Because purified C1q-R has a blocked amino terminus,
      amino acid sequences representing internal fragments of the molecule were
      generated by electroblotting and in situ enzymatic digestion. When these short
      sequences were searched against the National Biomedical Research Foundation
      computer data base, a seven-amino-acid sequence, VSWQGQI, showed significant
      homology (100% and 80% in a five-amino-acid overlap, respectively) with the alpha
      chains of the human fibronectin (alpha 5 beta 1) and vitronectin (alpha v beta 3)
      receptors, and to a lesser degree with epidermal growth factor receptor and T
      cell receptor. A second sequence, ISEDNIR, showed homology with mouse collagen
      type IV (86% in a six-amino-acid overlap), calmodulin (60% in a seven-amino-acid
      overlap), and a Leishmania major surface antigen, gp63. These observations seem
      to predict that C1q-R has pockets of conserved sequences that are similar to
      those not only present in its ligand(s) but also in other cell surface receptors
      that may, in part, fulfill similar functions.

PMID- 1377219
TI  - [Aggregation of erythrocyte suspensions of diabetic patients in dextran 70
      solutions].
AB  - Our previous studies have shown an erythrocyte hyperaggregation during diabetes.
      This hyperaggregation phenomenon seems usually be promoted by quantitative plasma
      protein's changes mainly fibrinogen. The aim of the present work is to appreciate
      the possible effect of only diabetic red cells on aggregation induced by dextran
      70 (Dx 70). Aggregation measurements were performed with Sefam aggregometer.
      Patients were insulin-dependent (IDD) and non insulin-dependent diabetics (NIDD),
      divided in two groups of 11 well controlled diabetics (HbA1C 6.8 +/- 0.5%) (7 IDD
      and 4 NIDD) and 11 poorly controlled diabetics (HbA1C 10.8 +/- 2.7%) (7 IDD and 4
      NIDD). They were compared with a control group consisting of 22 healthy subjects.
      Results can be summarized as follows: red cell aggregation induced by Dx 70 was
      not significantly different between the well controlled diabetics and controls.
      Similar results were obtained for the poorly controlled diabetics. By contrast,
      when studying red cell aggregation in autologous plasma (H = 40%), aggregation
      was found to be significantly more important in both diabetic groups than that of
      the controls. Thus, results emphasize the importance of suspending medium in
      erythrocyte hyper-aggregation phenomenon during diabetes. Cellular factors do not
      seem to interfere on aggregation phenomenon for diabetics included in this study.

PMID- 1377220
TI  - Enhanced neutrophil respiratory burst as a biological marker for manipulation
      forces: duration of the effect and association with substance P and tumor
      necrosis factor.

PMID- 1377221
TI  - Immunoreactive beta-core-like material in normal postmenopausal urine: human
      chorionic gonadotrophin or LH origin? Evidence for the existence of LH core.
AB  - Material with the immunochemical properties of the beta-core of human chorionic
      gonadotrophin (hCG) can be found in the urine of normal postmenopausal women.
      However, we have been unable to detect intact hCG (using an assay which is
      specific for the alpha-beta heterodimer of intact hCG) in serum of such subjects.
      The levels of serum LH and urinary beta-core were compared in matched samples
      from 28 women (serum LH: median 27 U/l, range 4-70 U/l, urinary beta-core: median
      0.27 microgram/l, range less than 0.05-0.645 microgram/l). Urine (4 litres) from
      three postmenopausal women was concentrated, dialysed and subjected to gel
      exclusion chromatography on Sephadex G-100. Fractions were analysed by specific
      assays for LH, intact hCG, total beta-hCG (free beta-subunit and intact hCG),
      free alpha-subunit and beta-core. Material eluting at the expected position of
      the beta-core fragment of hCG was detected in all three samples by the beta-core,
      beta-hCG and LH assays, despite the fact that the LH antibody does not recognize
      the authentic beta-core of pregnancy. Electrophoresis and Western blotting of the
      concentrated urines revealed that material of the same molecular size as beta
      core was recognized by the antibody to LH but not by a monoclonal antibody raised
      to free beta-hCG which also recognizes the beta-core molecule of hCG. We conclude
      that the predominant core-like material identified in postmenopausal urine is
      probably derived from the beta-subunit of LH.

PMID- 1377222
TI  - Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant
      vaccinia: implications for vaccine development.
AB  - There is considerable interest in designing an effective vaccine to the
      ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic
      T lymphocytes (CTLs) in eliminating virus-infected cells is well established.
      Limited studies using a small number of immune donors have defined target
      epitopes within the latent antigens of EBV. The present study provides an
      extensive analysis of the distribution of class I-restricted CTL epitopes within
      EBV-encoded proteins. Using recombinant vaccinia encoding individual EBV latent
      antigens (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, LP, and LMP 1),
      we have successfully localized target epitopes recognized by CTL clones from a
      panel of 14 EBV-immune donors. Of the 20 CTL epitopes localized, five were
      defined at the peptide level. Although CTL clones specific for nine epitopes
      recognized both type 1 and type 2 transformants, a significant number of epitopes
      (7/16 epitopes for which EBV type specificity was determined) were detected only
      on type 1 EBV transformants. Vaccinia recombinants encoding EBNA 3A and EBNA 3C
      were recognized more frequently than any other vaccinia recombinants used in this
      study, while no CTL epitopes were localized in EBNA 1. Surprisingly, epitope
      specificity for a large number of EBV-specific CTL clones could not be localized,
      although vaccinia recombinants used in this study encoded most of the latent
      antigens of EBV. These results suggest that any EBV vaccine based on CTL epitopes
      designed to provide widespread protection will need to include not only latent
      antigen sequences but also other regions of the genome. The apparent inability of
      human CTLs to recognize EBNA 1 as a target antigen, often the only latent antigen
      expressed in Burkitt's lymphoma and nasopharyngeal carcinoma, suggests that EBV
      specific CTL control of these tumors will not be feasible unless the down
      regulation of latent antigens can be reversed.

PMID- 1377223
TI  - Cloning and expression of Trypanosoma cruzi ribosomal protein P0 and epitope
      analysis of anti-P0 autoantibodies in Chagas' disease patients.
AB  - Chagas' disease, caused by the intracellular protozoan parasite Trypanosoma
      cruzi, is a major cause of heart failure in endemic areas. Antigenic mimicry by
      T. cruzi antigens sharing epitopes with host macromolecules has been implicated
      in the pathogenesis which is thought to have a significant autoimmune component.
      We report herein on the cloning and characterization of a full-length cDNA from a
      T. cruzi expression library encoding a protein, TcP0, that is homologous to the
      human 38-kD ribosomal phosphoprotein HuP0. The T. cruzi P0 protein shows a
      clustering of residues that are evolutionarily conserved in higher eukaryotes.
      This includes an alanine- and glycine-rich region adjacent to a highly charged
      COOH terminus. This "hallmark" domain is the basis of the crossreactivity of the
      highly immunogenic eukaryotic P protein family. We found that T. cruzi-infected
      individuals have antibodies reacting with host (self) P proteins, as well as with
      recombinant TcP0. Deletion of the six carboxy-terminal amino acids abolished the
      reactivity of the T. cruzi infection sera with TcP0. This is similar to the
      specificity of anti-P autoantibodies described for a subset of patients with
      systemic lupus erythematosus (SLE) (Elkon, K., E. Bonfa, R. Llovet, W. Danho, H.
      Weissbach, and N. Brot. 1988. Proc. Natl. Acad. Sci. USA. 85:5186). These results
      suggest that T. cruzi P proteins may contribute to the development of
      autoreactive antibodies in Chagas' disease, and that the underlying mechanisms of
      anti-P autoantibody may be similar in Chagas' and SLE patients. This study
      represents the first definitive report of the cloning of a full-length T. cruzi
      antigen that mimics a characterized host homologue in structure, function, and
      shared antigenicity.

PMID- 1377225
TI  - Stimulation of the nitric oxide synthase pathway in human hepatocytes by
      cytokines and endotoxin.
AB  - Nitric oxide (NO) is a short-lived biologic mediator that is shown to be induced
      in various cell types and to cause many metabolic changes in target cells.
      Inhibition of tumor cell growth and antimicrobial activity has been attributed to
      the stimulation of the inducible type of the NO synthase (NOS). However, there is
      limited evidence for the existence of such inducible NOS in a human cell type. We
      show here the induction of NO biosynthesis in freshly isolated human hepatocytes
      (HC) after stimulation with interleukin 1, tumor necrosis factor (TNF), IFN
      gamma, and endotoxin. Increased levels of nitrite (NO2-) and nitrate (NO3-) in
      culture supernatants were associated with NADPH-dependent NOS activity in the
      cell lysates. The production of NO2- and NO3- was inhibited by NG-monomethyl L
      arginine and was associated with an increase in cyclic guanylate monophosphate
      release. The data presented here provide evidence for the existence of typical
      inducible NO biosynthesis in a human cell type.

PMID- 1377224
TI  - CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta
      1 integrin-mediated adhesion.
AB  - The CD31 (platelet endothelial cell adhesion molecule-1 [PECAM-1]/endothelial
      cell adhesion molecule [endoCAM]) molecule expressed on leukocytes, platelets,
      and endothelial cells is postulated to mediate adhesion to endothelial cells and
      thereby function in immunity, inflammation, and wound healing. We report the
      following novel features of CD31 which suggests a role for it in adhesion
      amplification of unique T cell subsets: (a) engagement of CD31 induces the
      adhesive function of beta 1 and beta 2 integrins; (b) adhesion induction by CD31
      immunoglobulin G (IgG) monoclonal antibodies (mAbs) is sensitive, requiring only
      bivalent mAb; (c) CD31 mAb induces adhesion rapidly, but it is transient; (d)
      unique subsets of CD4+ and CD8+ T cells express CD31, including all naive
      (CD45RA+) CD8 T cells; and (e) CD31 induction is selective, inducing adhesive
      function of beta 1 integrins, particularly very late antigen-4, more efficiently
      than the beta 2 integrin lymphocyte function-associated antigen-1. Conversely,
      CD3 is more effective in inducing beta 2-mediated adhesion. Taken together, these
      findings indicate that unique T cell subsets express CD31, and CD31 has the
      capacity to induce integrin-mediated adhesion of T cells in a sensitive and
      selective fashion. We propose that, in collaboration with other
      receptors/ligands, CD31 functions in an "adhesion cascade" by amplifying integrin
      mediated adhesion of CD31+ T cells to other cells, particularly endothelial
      cells.

PMID- 1377226
TI  - In a small multideterminant peptide, each determinant is recognized by a
      different V beta gene segment.
AB  - Given the vast potential for diversification of the T cell receptor (TCR)
      repertoire and the fact that V(a) beta mice exist in the wild, it would have been
      predicted that in spite of the absence of 10 TCR V beta gene segments, V(a) beta
      mice would still have been able to produce an antigen-specific T cell response to
      all determinants. We have recently shown that Vb beta mice, with a wild-type TCR
      V beta repertoire, respond to peptide 110-121 of sperm whale myoglobin, with a
      majority of T cells expressing TCR V beta 8.2 and restricted to a hybrid I-A(d)/I
      E(d) major histocompatibility complex molecule, and a smaller number of T cells
      expressing TCR V beta 8.1 and restricted to the I-A(d) molecule. However, V(a)
      beta mice, lacking members of the TCR V beta 8 gene family, responded only with I
      A(d)-restricted T cells. Thus, it appeared that the I-A(d)-restricted response
      was less constrained, or more plastic. We now show that the two separate panels
      of I-A(d)-restricted T cell hybrids derived from V(a) beta or Vb beta mice in
      fact recognize distinct determinants within the same peptide 110-121. The
      determinant recognized by V(a) beta T cells is NH2 terminal (core: 110-118) with
      an absolute requirement for the residue Ala-110 for a successful interaction with
      TCRs. On the other hand, Vb beta T cells recognize the COOH-terminal region
      (core: 112-118) on the same peptide with an absolute requirement for COOH
      terminal residue 118. In the dominance hierarchy displayed by the three distinct
      determinants of peptide 110-121, V(a) beta mice cannot recognize the two most
      dominant: the hybrid I-A(d)/I-E(d)-restricted determinant and the COOH-terminal,
      I-A(d)-restricted determinant. They instead respond with T cells specific for a
      third, distinctly NH2-terminal determinant. Our results show a strict association
      between recognition of a particular specificity and TCR V beta usage. This
      evidence suggests that even when a small peptide induces a heterogenous group of
      TCR V beta S, this need not be considered evidence for plasticity. Rather, at the
      level of individual determinants within the peptide, the results can point in the
      opposite direction, towards serious constraints in recognition at the level of V
      beta expression.

PMID- 1377227
TI  - Identification of T cell epitopes occurring in a meningococcal class 1 outer
      membrane protein using overlapping peptides assembled with simultaneous multiple
      peptide synthesis.
AB  - The meningococcal class 1 outer membrane protein (OMP) plays an important role in
      the development of protective immunity against meningococcal infection, and is
      therefore considered to be a promising candidate antigen (Ag) for a meningococcal
      vaccine. The induction of an effective antibody response entirely depends upon T
      helper cells. To identify T cell epitopes of the OMP, we prepared 45 overlapping
      synthetic peptides representing the entire sequence of the class 1 protein of
      reference strain H44/76. Fully automated simultaneous multiple peptide synthesis
      (SMPS) was used to assemble the 45 twenty mer which overlapped by 12 amino acid
      residues on a 12 mumol scale. The peptides were tested for recognition by
      peripheral blood mononuclear cells (PBMC) obtained from 34 volunteers.
      Surprisingly, all synthetic peptides induced proliferative responses of PBMC
      isolated from one or more human histocompatibility leukocyte antigen (HLA)-typed
      immune adults. With PBMC from seven nonimmune donors, no proliferative response
      was observed. Immunodominant regions were found, recognized by PBMC from many
      volunteers, irrespective of their HLA type. Most of the immunodominant T cell
      epitopes are located outside the variable regions and, thus, will be conserved
      among different meningococcal (and gonococcal) strains. Furthermore, the
      overlapping peptides could be used to identify the epitopes recognized by OMP
      specific T cell clones with known HLA restriction. It is interesting that the
      epitopes defined with the clones occur in highly conserved areas, shared by all
      neisserial porin proteins. In summary, this analysis of the T cell response to
      the meningococcal class 1 OMP constitutes a complete study of reactivity to a
      foreign protein, and illustrates some important features of Ag recognition by T
      cells. Our data demonstrate unexpected diversity in the T cell recognition of the
      OMP, and imply that the T cell repertoire against foreign Ag may be greater than
      previously assumed. This observation is supported by recent data on the
      interaction of peptide and major histocompatibility complex (MHC) class II, the
      latter being much less selective than MHC class I. Finally, a comparative
      analysis pointed out the limitations of algorithms predicting T cell
      determinants, and the importance of the empirical methodology provided by SMPS.

PMID- 1377228
TI  - Activated endothelium binds lymphocytes through a novel binding site in the
      alternately spliced domain of vascular cell adhesion molecule-1.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) is induced on endothelial cells by
      inflammatory cytokines, and binds mononuclear leukocytes through the integrin
      very late antigen-4 (VLA-4) (alpha 4 beta 1). This adhesion pathway has been
      implicated in a diverse group of physiological and pathological processes,
      including B cell development, leukocyte activation and recruitment to sites of
      inflammation, atherosclerosis, and tumor cell metastasis. The major form of VCAM
      1 (VCAM-7D) has seven extracellular immunoglobulin (Ig)-like domains, of which
      the three NH2-terminal domains (domains 1-3) are similar in amino acid sequence
      to domains 4-6. By functional analysis of VCAM-7D relative to VCAM-6D (a minor 6
      domain form of VCAM-1 in which domain 4 is deleted because of alternative
      splicing), and chimeric constructs between VCAM-1 and its structural relative
      intercellular adhesion molecule-1 (ICAM-1), we show that either the first or the
      homologous fourth domain of VCAM-1 is required for VLA-4-dependent adhesion.
      Either of these binding sites can function in the absence of the other. When both
      are present, cell binding activity is increased relative to monovalent forms of
      the molecule. The homologous binding regions appear to have originated by
      internal duplication of a portion of a monovalent ancestral gene, before the
      mammalian radiation. Thus VCAM-1 exemplifies evolution of a functionally bivalent
      cell-cell adhesion molecule by intergenic duplication. We have also produced a
      new class of anti-VCAM-1 monoclonal antibodies that block domain 4-dependent
      adhesion, and demonstrate that both binding sites participate in the adhesion
      function of VCAM-1 on endothelial cells in vitro. Therefore both sites must be
      blocked in clinical, animal, or in vitro studies depending on the use of anti
      VCAM-1 antibodies to inactivate the VCAM-1/VLA-4 adhesion pathway.

PMID- 1377229
TI  - Development of an antiserum to the midportion of substance P: applications for
      biochemical and anatomical studies of substance P-related peptide species in CNS
      tissues.
AB  - This report describes the generation and biochemical characterization of a high
      affinity antiserum that recognizes an epitope contained in the midportion
      sequence of substance P, i.e., substance P4-10. Designated A47, this reagent
      bound a variety of related peptide species containing the substance P4-10
      sequence with apparent equipotency. A double radioimmunoassay procedure was
      developed that utilized A47, in combination with a traditional high-affinity COOH
      terminally directed anti-substance P serum, to provide quantification of mature
      and immature forms of substance P in CNS tissues. Across most rat CNS areas,
      levels of substance P-like immunoreactivity were consistently 15% higher when
      monitored by analyses using A47 versus anti-substance P serum. In the dorsal root
      ganglia, an apparent enhancement in levels of substance P-like immunoreactivity
      of approximately 40%, when quantified by analyses using A47 versus anti-substance
      P serum, was observed; this most likely reflected the presence of an active
      biosynthetic pool of intermediate processing forms of substance P in this tissue.
      Coordinated HPLC/radioimmunoassay analyses of extracted dorsal root ganglia
      tissues demonstrated multiple peaks of immunoreactivity corresponding to mature
      substance P and to several of its precursor forms found in the normal
      biosynthetic pathway. Of the total recovered HPLC-fractionated
      immunoreactivities, that corresponding to the putative immediate precursor to
      substance P, i.e., substance P-glycine, was the predominant peak. In an
      additional series of HPLC/radioimmunoassay analyses, selective decreases in
      immunoreactive peaks corresponding to precursor forms of substance P were
      observed in dorsal root ganglia tissues from rats treated with the neurotoxic
      agent capsaicin. These results indicated decreased turnover of substance P as a
      consequence of drug treatment. Finally, initial immunohistochemical analyses
      employing affinity-purified A47 produced an unusual pattern of labeling
      characterized by well defined punctate terminal elements within the superficial
      aspects of the dorsal horn of the spinal cord.

PMID- 1377230
TI  - Growth factor (M-CSF) and antigenic properties of macrophages in meningioma.
AB  - In meningiomas, transformed meningeal cells can share morphological aspects (in
      hemangiopericytic meningioma) and antigenic properties (i.e.: HLA-DR antigens
      expression) with elements of the monocyte/macrophage lineage. In this report, we
      describe a case of a highly vascular meningioma where numerous tumor cells,
      studied with immunohistochemical methods, present phenotypic properties of
      macrophages. Moreover, the cerebrospinal fluid (CF) analysis disclosed, using a
      biological assay, a high level of a growth factor for monocytic elements, the
      Macrophages Colony Stimulating Factor (M-CSF). Our findings may confirm that
      transitional aspects between different mesenchymal cells could be present in
      meningiomas.

PMID- 1377232
TI  - Olfactory receptor neurons from antennae of developing male Manduca sexta respond
      to components of the species-specific sex pheromone in vitro.
AB  - Male-specific olfactory receptor neurons, dissociated from developing antennae of
      the moth Manduca sexta and grown in long-term primary cell culture, can respond
      to at least one component of the female moth's sex-pheromone blend with the
      opening of a nonspecific cation channel. This response does not require the
      coapplication of pheromone-binding protein.

PMID- 1377231
TI  - Spatiotemporal increases in epidermal growth factor receptors following
      peripheral nerve injury.
AB  - Non-neuronal cells of peripheral nerve respond to axonal injury with a series of
      cellular changes that facilitate neuronal regeneration. To characterize the
      potential role of the epidermal growth factor (EGF) family of proteins in this
      response, we monitored the expression of EGF receptor mRNA and protein in the
      injured rat sciatic nerve. EGF receptor mRNA is synthesized in both primary
      cultured fibroblasts and Schwann cells, and Schwann cells express EGF receptor
      like immunoreactivity. In situ hybridization and immunocytochemistry revealed
      that EGF receptor mRNA and protein are expressed in Schwann cells and fibroblasts
      of the sciatic nerve in vivo, and that receptor levels increase following nerve
      injury. Thirty-six hours postlesion, EGF receptors were expressed in gradients
      along the nerve both proximal and distal to the lesion, with the highest levels
      localized adjacent to the transection site. By 72 hr, receptor levels were
      maintained in a gradient in the proximal segment, but were uniformly increased
      throughout the portions of the distal segment that were analyzed. These changes
      were similar to those observed for low-affinity NGF receptor mRNA and protein,
      with transection causing increased expression in both Schwann cells and
      fibroblasts. Northern blots confirmed that primary cultured fibroblasts express
      low-affinity NGF receptor mRNA. To determine whether spatiotemporal gradients
      were a general characteristic of the nerve injury response, we monitored
      expression of the mRNA encoding the major myelin protein P0. Levels of P0 mRNA
      decreased initially in cells immediately adjacent to the transection site and, by
      72 hr, were uniformly decreased throughout the distal segment. These data suggest
      that members of the EGF family of proteins may play a role in the peripheral
      nerve response to injury, and demonstrate a generalized gradient of cellular
      responses that commence at the transection site and progress distally in the
      nerve in the absence of intact axons.

PMID- 1377233
TI  - NGF induces the expression of the VGF gene through a cAMP response element.
AB  - NGF is a peptide growth factor that plays a key role in the differentiation and
      survival of neurons in both the PNS and CNS. NGF acts through both transcription
      dependent and transcription-independent mechanisms to regulate the
      differentiation of PC12 cells. To better understand the regulation of gene
      expression by NGF, we have defined a cis-acting sequence that is immediately
      upstream of the transcription start site of the VGF (a2/NGF33.1) gene that is
      required for induction by NGF. Within this sequence is a consensus cAMP response
      element (CRE) embedded in a 14 base pair palindrome. Mutations in this CRE
      eliminate induction of the VGF gene both by NGF and by agents that act via cAMP.
      Although this sequence confers transcriptional induction by both NGF and cAMP, it
      is not sufficient to allow induction by epidermal growth factor, acidic or basic
      fibroblast growth factor, or phorbol 12-myristate 13-acetate (PMA). Thus, this
      sequence defines an element that is selectively activated by NGF and cAMP.
      Promoter fragments from the VGF gene that include the core CRE efficiently bind
      the inducible transcription factor CREB, while fragments bearing mutations that
      eliminate NGF and cAMP inducibility fail to do so. Sequence comparisons and
      hybridization studies indicate that there are at least two alternatively spliced
      forms of VGF mRNA, and the accumulation of both of these forms is similarly
      regulated by NGF and cAMP.

PMID- 1377234
TI  - Tumor necrosis factor modulates Ca2+ currents in cultured sympathetic neurons.
AB  - The effect of recombinant human tumor necrosis factor-alpha (rhTNF) on calcium
      currents of cultured neurons from neonatal rat superior cervical ganglia (SCG)
      was studied using whole-cell patch-clamp technique. We found that rhTNF-treated
      SCG neurons exhibited increased calcium current density without significant
      alteration in the steady-state parameters of activation and availability. The
      fraction of the current sensitive to dihydropyridines and omega-conotoxin also
      remained unchanged. Recovery from slow inactivation of the current, but not
      recovery from fast inactivation, was prolonged in rhTNF-treated cells when
      compared to that of control cells. We conclude that immune peptides such as rhTNF
      can alter cellular functions of sympathetic neurons via modulating ionic
      conductances. However, these changes observed in calcium currents of SCG neurons
      cannot account for the effect of rhTNF on norepinephrine secretion observed in a
      previous study. It is proposed that rhTNF exerts an additional effect at a later
      event in the exocytotic process.

PMID- 1377235
TI  - The lack of effect of basic and acidic fibroblast growth factors on the naturally
      occurring death of neurons in the chick embryo.
AB  - In vivo treatment of developing chick embryos with acidic and basic fibroblast
      growth factors (aFGF and bFGF) failed to affect the differentiation and survival
      of several populations of developing neurons in the CNS and PNS. All of the
      neuronal populations examined are known to undergo naturally occurring cell
      death, and they include spinal and cranial motoneurons, dorsal root ganglia,
      sympathetic ganglia, nodose ganglia, ciliary ganglia, and sympathetic
      preganglionic neurons in the PNS, as well as the accessory oculomotor nucleus,
      the isthmo-optic nucleus, and the brainstem auditory nuclei laminaris and
      magnocellularis in the CNS. Despite the lack of effect of bFGF on neuronal
      survival and differentiation, in vivo treatment increased the serum levels of
      bFGF and stimulated the proliferation of non-neuronal cells in the spinal cord.
      Therefore, although the administration of exogenous FGF to the developing chick
      embryo in vivo clearly has some biological activity in the CNS, it was
      nonetheless ineffective in promoting neuronal survival or differentiation. These
      data do not support the idea that FGF is a physiologically relevant neurotrophic
      agent in the developing avian nervous system.

PMID- 1377236
TI  - Intrinsic lattice connections of macaque monkey visual cortical area V4.
AB  - We made focal iontophoretic as well as larger pressure injections (n = 30; 19
      used for most analyses) of the tracer biocytin in visual area V4 of six macaque
      monkeys. The resulting transported label enabled mapping of intrinsic inter- and
      intralaminar connections within the region. We found that pyramidal neurons of
      layers 2 and 3 make extensive lateral projections within area V4, with oval or
      circular patches of terminals in layers 1-3. Any small patch of tissue
      (approximately 250 microns wide) injected in the superficial layers appeared to
      connect reciprocally to patches scattered up to 3 mm around the injection. The
      patches of terminal label measure 250-450 microns across, spaced roughly 600
      microns (range, 450-1300 microns) center to center, and where most densely packed
      they occupy 33% of the cortical area with approximately 3-4 patches/mm2. Small
      injections in layers 4 and 6 did not produce contributions to these patchlike
      lattice connections, while injections in layer 5 gave very weak rising
      contributions to the superficial layer patch system. Large pressure injections of
      biocytin gave wider spread and more densely labeled patches, but their size and
      spacing appeared much the same as with small injections. The V4 pattern of label
      was compared to the patterns seen in areas V1 and V2 after similar-sized
      injections of biocytin; patches in V1 and V2 were slightly smaller (roughly 250
      300 microns across) and more closely spaced (425-450 microns center to center),
      consistent with earlier measures in these areas using HRP. The peak areal
      occupancy of patches was approximately the same, 27-33% in each region. We
      interpret these findings as indicating a functional repeat distance of 450-600
      microns in area V4 (fixed tissue measures) with a patchy, discontinuous layout.
      Given the dimensions of the V4 intrinsic connectional system demonstrated here,
      it seems unlikely that it relates directly to the topography of specific afferent
      terminations or efferent neuron groups, which appear from other studies to have a
      larger scale of repeat (2-3 mm). However, patches in V4 tend to aggregate,
      forming clusters extended in the mediolateral direction, suggesting a possible
      relation to coarser connection zones.

PMID- 1377237
TI  - A signal sequence mediates the retrograde transport of proteins from the axon
      periphery to the cell body and then into the nucleus.
AB  - The presynaptic terminal and axon of neurons can undergo structural changes in
      response to environmental signals. Since these changes require protein synthesis
      in the cell body, the needs of the periphery must somehow be communicated to the
      cell soma. To look for such a mechanism, we used artificial protein constructs
      with properties expected of a signal that is transported from the axon to the
      nucleus. One construct consisted of the nuclear import signal peptide (sp) of the
      SV40 large T antigen, coupled to human serum albumin (HSA) and rhodamine (r).
      When injected into the axoplasm of Aplysia californica neurons in vitro, the rHSA
      sp was transported in the retrograde direction through the axon to the cell body
      and then into the nucleus. Little, if any, moved in the anterograde direction
      toward growth cones. The retrograde movement of injected rHSA-sp was rapid
      (greater than 25 mm/d) and depended upon intact microtubules. The sp portion of
      rHSA-sp provided access to both the retrograde transport system and the nuclear
      import apparatus. Thus, rHSA was not transported at all, but accumulated in
      organelles near the injection site. Also, rHSA-sp containing an sp with a Lys to
      Thr substitution, which is known to reduce nuclear import markedly, was
      transported only poorly. To look for endogenous molecules that use this system,
      we affinity-purified a rabbit polyclonal antibody to the signal sequence. The
      antibody recognized an 83 kDa polypeptide on Western blots of Aplysia nervous
      tissue. These data indicate that Aplysia neurons contain the machinery to convey
      macromolecules from the axon periphery to the nucleus.

PMID- 1377238
TI  - Developmental changes in calcium conductances contribute to the physiological
      maturation of cerebellar Purkinje neurons in culture.
AB  - The relationship between calcium conductances and developmental changes in the
      active and passive membrane properties of cerebellar Purkinje neurons from rats
      was studied in a culture model system by using current-clamp and voltage-clamp
      techniques. These cultures, at 6-21 d of age, represented the main period of
      morphological and physiological development of the Purkinje neuron. In the
      current-clamp studies, input resistance decreased and the current-voltage curve
      became more S-shaped as the neurons matured in culture. Spike-generating
      properties also changed. Immature Purkinje neurons without dendritic structure
      produced repetitive, fast TTX-sensitive simple spikes when stimulated
      electrically. The simple spike frequency increased with maturation. In older
      neurons (greater than or equal to 12 d in vitro) with well-developed dendritic
      structure, a burst event, the complex spike, preceded the repetitive simple spike
      firing. Magnesium (10 mM) and cadmium (50-100 microM), calcium channel blockers,
      antagonized the repetitive simple spike firing in both young and old neurons. The
      complex spike of the older neurons was also antagonized by magnesium (10 mM) but
      was resistant to cadmium (50-100 microM), suggesting that a pharmacologically
      distinct calcium conductance mediated this spike event. Whole-cell voltage-clamp
      recordings showed that the older Purkinje neurons expressed two calcium currents,
      a low-threshold rapidly inactivating calcium current resistant to cadmium (50-100
      microM) and a high-threshold slowly inactivating calcium current antagonized by
      cadmium (50-100 microM). In young Purkinje neurons without dendritic structure (6
      9 d in vitro), only the high-threshold calcium current was evident. The amplitude
      of this current increased approximately 50% during development. These results
      indicate that the developmental expression of calcium conductances plays a
      prominent role in the physiological maturation of the cultured Purkinje neurons,
      which closely simulate the physiologic cells they model. The high-threshold
      calcium conductance is expressed early in development and contributes to
      repetitive simple spike firing of both the young and old neurons. The low
      threshold calcium conductance appears later in development, coincident with
      dendritic expression, and plays a major role in the generation of the complex
      spike.

PMID- 1377239
TI  - Immunological analysis of proteoglycan structural changes in the early stage of
      experimental osteoarthritic canine cartilage lesions.
AB  - Specific modifications of the proteoglycan (PG) structure of osteoarthritic (OA)
      dog cartilage in relation to endogenous metalloprotease activity were examined
      using murine anti-proteoglycan monoclonal antibodies (MoAbs). OA lesions were
      induced over a period of 8 weeks in crossbred dogs (Pond-Nuki model). The
      articular cartilage was removed and homogenized in a Tris buffer, pH 7.5, and
      then divided into four groups: direct PG extraction, no addition, presence of 1
      mM p-aminophenyl mercuric acetate (APMA), and presence of 1 mM APMA and 10 mM o
      phenanthroline, incubated for 42 h at 37 degrees C followed by PG extraction.
      MoAbs reactive with PG protein and carbohydrate epitopes included 1C6, 3B3, 5D4,
      D1B2, and m4D6. The results showed marked alterations induced by APMA activation
      of the endogenous metalloproteases. PG changes were apparent at at least three
      sites: one was either in the hyaluronic acid-binding region or between the
      hyaluronic-binding region and the G2 globular domain, another was between the
      keratan-sulfate-rich domain and the chondroitin sulfate-attachment domain, and a
      third was in the chondroitin sulfate-attachment domain. Constitutive
      metalloprotease activity resulted in less marked PG alterations with preservation
      of functional PG aggregation to hyaluronan.

PMID- 1377240
TI  - Immunohistochemical localization of beta 1-integrins in anterior cruciate and
      medial collateral ligaments of human and rabbit.
AB  - The integrins are a family of adhesion-mediating cell surface receptors that play
      critical roles in cell-extracellular matrix interactions and have been shown to
      be important in the healing response in several tissues. We have studied integrin
      expression in normal human and rabbit anterior cruciate (ACL) and medial
      collateral (MCL) ligaments of the knee as a preamble to studies of beta 1
      integrin expression in healing ligaments. Histologic sections of human and rabbit
      ACL and MCL were probed for integrin expression utilizing integrin-specific
      monoclonal antibodies (mAbs) followed by immunoperoxidase detection. Staining of
      human specimens with mAbs revealed the presence of beta 1-, alpha 1-, and alpha 5
      integrin chains on the tissue fibroblasts of both ACL and MCL, while staining of
      rabbit specimens with rabbit integrin-reactive monoclonals revealed the presence
      of beta 1- and alpha 5-integrin on these ligaments. Equivalent amounts of the
      integrins studied were present on normal ACL and MCL. We conclude that the rabbit
      is an appropriate model for analyzing the expression and functional role of
      integrins in ligament wound healing.

PMID- 1377242
TI  - Oesophageal replacement in paediatric patients.
AB  - Over a 5-year period from January 1986 to December 1990, 24 children aged between
      16 months and 12 years with undilatable oesophageal stricture had oesophageal
      replacement with isoperistaltic colonic conduit. All the strictures followed
      accidental corrosive burns. The procedure was well tolerated; all the patients
      were able to swallow within 3 weeks of surgery. Major postoperative complications
      were threatening pneumothorax (two cases), gastric outlet obstruction due to
      Ascaris lumbricoides (two cases) and cervical fistula (eight cases) which closed
      spontaneously in each case. There were no operative or postoperative deaths.
      Twenty-two patients have been followed up for 2-59 months. Children tolerate
      oesophageal replacement well. The short-term and medium-term results are good,
      but anxiety over the fate of the retained native oesophagus is noted.

PMID- 1377241
TI  - Epitope mapping of HIV-1 reverse transcriptase with monoclonal antibodies that
      inhibit polymerase and RNase H activities.
AB  - Lysates from E. coli expressing HIV-1 reverse transcriptase (RT) as a TrpE fusion
      protein were used for immunization of BALB/c mice. Twenty hybridomas producing
      monoclonal antibodies (MAbs) recognizing the RT part of the TrpE-RT fusion
      protein by Western blot analysis were isolated. Of these, 18 were reactive in
      immunofluorescence assays when tested on HIV-infected cells. Twelve MAbs were
      reactive with both the p66 and p51 fragments of RT, while 6 of the MAbs were
      reactive only with the p66 band, indicating specificity for the C-terminal (RNase
      H) region of RT. Mapping of the monoclonal antibody binding sites was performed
      using deletion and insertion mutants of recombinant RT. The antibodies bound to
      five distinct regions within amino acid sequences 190-560 of RT. In order to map
      functionally important regions of the RT molecule, the MAbs were tested for their
      ability to interfere with the polymerase and RNase H activities of the
      polypeptide. MAbs binding to two different epitopes in the polymerase domain were
      found to inhibit the polymerase activity. Of these, three MAbs also inhibited the
      RNase H activity. Two MAbs binding to the same epitope in the RNase H region
      inhibited RNase H activity and further mediated an effect on the polymerase
      activity.

PMID- 1377243
TI  - Variation among trainee surgeons in interpreting diagnostic peritoneal lavage
      fluid in blunt abdominal trauma.
AB  - Diagnostic peritoneal lavage is useful in selected patients who have sustained
      blunt abdominal trauma. The way in which 50 trainee surgeons (37 registrars and
      13 senior registrars) perform and interpret diagnostic peritoneal lavage was
      investigated in this study by a simple questionnaire followed by assessment of
      simulated lavage fluid. This exposed misconceptions about interpretation of
      diagnostic peritoneal lavage fluid and a reliance upon visual assessment.
      Assessment of the simulated lavage fluid revealed a wide range of thresholds for
      a positive result (2460-48,700 red blood cells/mm3), although 49 surgeons (98%)
      had lower thresholds than that generally recommended. Senior registrars had
      significantly higher thresholds than registrars, implying a learning curve
      involving unnecessary laparotomies. In order to avoid this situation and to
      detect injuries that might otherwise be missed, trainee surgeons are recommended
      to perform cell count analysis routinely on diagnostic peritoneal lavage fluid.

PMID- 1377244
TI  - Diverticular disease of the colon in black Africa.
AB  - Diverticular disease of the colon, previously believed to be rare among Africans,
      is now an emerging disease entity in many areas of the African tropics. Fifteen
      patients, the majority of whom were overweight (73%), under 50 years of age (73%)
      and who have remained on the bulky diet traditional to much of Africa, are
      reported. The findings suggest that factors previously uncommon in the area may
      now be operating to cause the disease in the population, and the highly processed
      food products of the supermarkets may be an important contributor to the
      development of this new disease entity.

PMID- 1377245
TI  - Antibiotic prophylaxis in acute non-perforated appendicitis in children: single
      dose of metronidazole and gentamicin.
AB  - In a 3-year study, 103 children with acute non-perforated appendicitis who
      underwent appendicectomy were randomized for either a single preoperative dose of
      gentamicin and metronidazole or three doses of gentamicin and metronidazole given
      before and after the operation. The overall wound infection rate was 1.9%. There
      was no significant difference between wound infection rates of the single-dose
      group (2.1%) and the three-dose group (1.8%). The mean(s.d.) hospital stays of
      the single-dose and three-dose groups were similar: 6.6(2.2) days and 6.4(2.7)
      days. This study shows that a single preoperative dose of gentamicin and
      metronidazole is as effective as three doses of gentamicin and metronidazole in
      the control of post-appendicectomy wound sepsis.

PMID- 1377247
TI  - Surgery in collective protection against chemical warfare.
AB  - In the 3 months from October 1990 to January 1991, 110 operations were performed
      at 33 Field Hospital, Royal Army Medical Corps at Al Jubayl, Saudi Arabia in
      collective protection against chemical warfare. The evolution of improvements in
      this environment is presented in the context of the first operative series
      undertaken.

PMID- 1377246
TI  - Computed tomography for oesophageal carcinoma: its value to the surgeon.
AB  - Between January 1988 and June 1991, 75 patients with carcinoma of the oesophagus
      or gastro-oesophageal junction were evaluated by computed tomography (CT). Fifty
      of these patients underwent operation, allowing 48 cases to have a detailed
      surgical and pathological verification of CT features. For thoracic oesophageal
      tumours the accuracy of CT was 59% for fat plane status, 86% for aortic contact,
      81% for tracheobronchial tree compression and 66% for direct local invasion. CT
      was 69% accurate for identifying lymph nodes, of which only 38% contained
      metastatic deposits. For gastro-oesophageal junction tumours, CT was 74% accurate
      for fat plane status and 90% accurate for direct local invasion. Accuracy for
      detecting lymph node involvement was 63%, metastatic tumour being present in 91%
      of these nodes. By pathological staging, only 15% of all resections could be
      considered potentially curative. The value of CT was found to be in predicting a
      palliative or curative resection, and in warning the surgeon about possible
      infiltration of specific mediastinal or abdominal structures that would be
      encountered during operative dissection.

PMID- 1377248
TI  - Disc battery ingestion: a review and a management plan.

PMID- 1377249
TI  - Case of bilateral superior gluteal artery aneurysm.

PMID- 1377250
TI  - Implantable venous access catheters: what the patients say.

PMID- 1377251
TI  - Trauma care in the UK--the debate must continue.

PMID- 1377252
TI  - Estimating trauma centre workload.
AB  - To estimate the volume of major trauma seen in the UK in the light of the recent
      report from the Royal College of Surgeons of England, all publications relating
      to UK trauma practice published since the report were analysed. Major trauma
      represents one in every 1000 accident and emergency department attendances on
      average. Although this is less than in the USA, the severity of injury is at
      least equivalent to North American practice.

PMID- 1377253
TI  - New technique for assessing muscle damage after trauma.
AB  - We report a new technique which is a useful objective method for assessing the
      extent and severity of traumatic muscle damage using scintigraphic imaging.
      Radionuclide indium-111 antimyosin was used in 13 patients with trauma. The
      increased uptake was confined to the injured muscles and the intensity was
      related to the severity of damage.

PMID- 1377254
TI  - Modified 'K'-wire pliers.

PMID- 1377255
TI  - Amputation for gangrene of the limbs following severe meningococcal infection.

PMID- 1377256
TI  - Colorectal anastomotic integrity after anterior resection: is there a role for
      intraoperative testing?

PMID- 1377257
TI  - Postlaminectomy arteriovenous fistula formation: a continuing problem.

PMID- 1377258
TI  - Removal of Moore's pins.

PMID- 1377259
TI  - Capitellocondylar total elbow replacement for rheumatoid arthritis.

PMID- 1377260
TI  - Familial breast cancer.

PMID- 1377261
TI  - Comparison of postpyloromyotomy feeding regimens in infantile hypertrophic
      pyloric stenosis.

PMID- 1377262
TI  - Gangrene of the foot following peripheral phlebography.

PMID- 1377263
TI  - Squamous cell carcinoma of the renal pelvis associated with urinary diversion and
      humoral hypercalcaemic malignancy syndrome.

PMID- 1377264
TI  - Factors affecting limb salvage and mortality in patients undergoing femoral
      embolectomy.

PMID- 1377265
TI  - Surgical decompression of the carpal tunnel using infiltrative anaesthesia:
      description of technique.

PMID- 1377266
TI  - Barrett's oesophagus.

PMID- 1377267
TI  - Relationships between surgical ability ratings and spatial abilities and
      personality.
AB  - Twenty-two trainee surgeons were tested on high level tests of intelligence, a
      detailed battery of paper-and-pencil and computerized spatial ability tests, and
      personality tests. They were also rated for operating ability, clinical decision
      making ability, and for overall performance by consultant surgeons who knew them
      well. Ability ratings were high, indicating very little dissatisfaction with the
      performance of trainee surgeons. There were no significant correlations between
      surgical ability ratings and intelligence test scores. The only significant
      correlation between spatial ability and ability ratings was with one subtest, and
      was in the opposite direction to that expected. Trends in the data suggested that
      those trainees rated as superior tended to be more introverted and conscientious,
      and tended to have better stereoscopic depth perception. The discussion questions
      the necessity for aptitude testing in surgery and points out some statistical
      pitfalls in the area. It is concluded that little advance may be made with the
      application of aptitude testing in the selection of surgeons until there are more
      objective criteria of surgical ability in different surgical specialties.

PMID- 1377268
TI  - Aetiological role of otolaryngological disease in paediatric intracranial
      abscess.
AB  - Recent reports suggest that congenital heart disease has supplanted
      otolaryngological disease as the major aetiological factor in the development of
      paediatric intracranial abscess. A survey of intracranial abscess identified from
      the records of the Information and Statistics Division of the Scottish Health
      Service Common Services Agency and the departmental records of the regional
      neurosurgical units in Scotland for the period 1981-1985 was undertaken to test
      this hypothesis. A total of 22 cases in individuals under the age of 16 years
      confirmed at surgery or autopsy were classified aetiologically on the basis of
      localization, clinical and investigative findings. Three were cardiogenic, four
      otogenic and three rhinosinugenic in origin; the others were due to miscellaneous
      causes. The mean(s.d.) age was 9(4.5) years. The overall mortality rate was 18%.
      Otolaryngological disease is the major aetiological factor in paediatric
      intracranial abscess in the UK.

PMID- 1377269
TI  - Cryotherapy for retinopathy of prematurity in a regional neonatal intensive care
      unit.
AB  - Ninety-six low birth-weight premature infants at risk of retinopathy of
      prematurity (ROP) were screened over a 25-month period, yielding 30 eyes of 15
      infants with 'treatable' disease. The response and complications of cryotherapy
      were prospectively evaluated in these infants over a 3-24-month period. Six eyes
      of three infants progressed to cicatricial disease despite treatment. One infant
      developed angle closure glaucoma but neither eye showed cicatricial disease. In
      24 eyes of 12 infants regression of active ROP was observed after treatment. The
      local and systemic complications associated with cryotherapy are discussed.

PMID- 1377270
TI  - Parotid gland tumours: a 15-year experience.
AB  - Between 1973 and 1988, 302 patients underwent surgical operations for parotid
      gland swelling. Primary operations were performed in 293 cases, while secondary
      operations for recurrent tumour were performed in nine cases. A total of 244
      patients (80.8%) were found histologically to have either a benign parotid tumour
      or a tumour-like lesion, while 58 patients (19.2%) were diagnosed as having
      malignant tumours. Two hundred and eighty-nine patients underwent superficial and
      total conservative parotidectomy and in 13 cases a radical parotidectomy was
      performed. The median follow-up was 5 years (range 1-15 years). Permanent facial
      nerve palsy, tumour recurrence, Frey's syndrome and parotid fistula were recorded
      as 0.7, 0.7, 2.1 and 0.4%, respectively. Thus, with full understanding of the
      surgical anatomy of the parotid gland and correct tumour identification,
      preservation of the facial nerve and serious postoperative complications can be
      minimized following superficial and/or total conservative parotidectomy.

PMID- 1377271
TI  - PDS II (polydioxanone) is the monofilament suture of choice for subcuticular
      wound closure following breast biopsy.
AB  - In a randomized study of 120 patients having a local anesthetic breast biopsy,
      wounds closed with subcuticular PDS II were cosmetically superior to those closed
      by Prolene.

PMID- 1377272
TI  - Paraoesophageal hiatal hernias: when to operate.
AB  - Between 1979 and 1988, 29 cases of paraoesophageal hernia presented to one
      surgeon (F.D.S.). There were 23 women and six men and the mean(s.e.m.) age was
      66.3(4.1) years. All were symptomatic and 13 hernias (45%) were complicated by
      gastric volvulus, haemorrhage or perforation. Ten (34%) had evidence of gastro
      oesophageal reflux, suggesting a sliding component in these cases. Operation,
      mostly transthoracic, consisted of hernial reduction, crural repair and, if
      indicated, an antireflux procedure. There were three deaths. Two occurred as a
      result of spontaneous, intrathoracic perforation of the hernia. The third
      followed dilatation of a benign stricture 2 months after surgery. The only major
      complication was a pulmonary embolus with full recovery. The mean(s.e.m.) follow
      up time was 47.6(7.8) months and there were no recurrences. This series confirms
      that symptomatic paraoesophageal hernias warrant early repair because of the
      frequency and severity of associated complications. Although debate continues as
      to whether this policy should be extended to asymptomatic paraoesophageal
      hernias, we suggest that this should be so.

PMID- 1377273
TI  - Case-control study of patient satisfaction with day-case and inpatient inguinal
      hernia repair.
AB  - A case-control study has been carried out to assess patient satisfaction with day
      case or inpatient inguinal hernia repair using matched pairs of patients
      undergoing the same technique of inguinal hernia repair under general
      anaesthesia. Patients completed a single-page questionnaire 3-6 months after
      surgery. Although there was no objective difference in recovery, nearly half of
      the patients felt that they were discharged too early and the majority would
      prefer inpatient treatment. Day-case patients required significantly more medical
      attention after discharge and most of the reported wound complications were not
      known to the hospital. It is concluded that the introduction of day-case surgery
      in a district general hospital is not without problems and requires changes in
      working practices and resource availability with careful monitoring of outcome
      during its implementation.

PMID- 1377274
TI  - Abnormalities of T lymphocyte subsets in Behcet's disease demonstrated with anti
      CD45RA and anti-CD29 monoclonal antibodies.
AB  - We assessed T cell subpopulations using 2-color flow cytometry with phycoerythrin
      conjugated anti-CD45RA and anti-CD29 and fluorescein conjugated anti-CD4 and anti
      CD8 monoclonal antibodies, on peripheral blood lymphocytes from 19 patients with
      Behcet's disease (BD) and 18 healthy control subjects. The percentage of CD4+
      cells was significantly lower in patients with BD (34 +/- 2%) than in control
      subjects (46 +/- 3%) (p less than 0.001). Among CD4+ cells, the percentage of
      suppressor-inducer (CD4+CD45RA+) cells was significantly lower in patients with
      BD (31 +/- 4%) than in control subjects (45 +/- 2%) (p less than 0.01), while the
      percentages of helper-inducer (CD4+CD29+) cells were similar in patients and
      controls. The percentage of CD8+ cells was significantly higher in patients with
      BD (36 +/- 2%) than in control subjects (26 +/- 2%) (p less than 0.001) involving
      both CD45RA+ and CD29+ subpopulations. Within CD4+ cells, the percentage of
      suppressor-inducer (CD4+CD45RA+) cells was significantly decreased in patients
      with active BD (26 +/- 3%) compared with control subjects (45 +/- 2%) (p less
      than 0.001), whereas in patients with inactive BD the difference was
      statistically insignificant. Our results suggest that the defective suppressive
      function in patients with active BD may be related to the decreased suppressor
      inducer subpopulation (CD4+CD45RA+).

PMID- 1377275
TI  - HLA associations with rheumatoid arthritis: a piece of the puzzle.
AB  - HLA molecules play a central role in the immune response by presenting processed
      antigenic peptides to T cells. In the case of rheumatoid arthritis (RA), a
      specific sequence present within the peptide binding cleft of HLA class II
      molecules has been implicated in genetic susceptibility to this disease. Several
      mechanisms could account for this finding. One possibility, designated
      determinant selection, rests on the possibility that HLA molecules associated
      with RA may bind a distinct set of foreign or self antigens that can trigger a T
      cell response in the joint. Alternatively, HLA molecules may predispose to RA by
      shaping the T cell repertoire during thymic differentiation in neonatal and early
      adult life. These 2 mechanisms are not mutually exclusive, and it must be
      remembered that several other susceptibility genes as well as environmental
      factors remain to be identified before a comprehensive understanding of RA is
      achieved.

PMID- 1377277
TI  - The 14th C. L. Oakley Lecture. Candida albicans HSP 90: link between protective
      and auto immunity.
AB  - Heat shock proteins (HSP) are thought to play a role in the aetiology of
      autoimmune diseases, but are also common targets for the immune response to many
      infections. Patients recovering from systemic candidosis produce antibodies to
      Candida albicans HSP 90, both to species-specific epitopes and, more commonly, to
      epitopes shared with human HSP 90. One such autoreactive antibody was protective
      in a mouse model of systemic candidosis.

PMID- 1377276
TI  - Cystic fibrosis mutations delta F508 and G542X in Jewish patients.
AB  - We have screened our CF patients for mutations in exons 10 and 11 of the CFTR
      gene. Two mutations, delta F508 and G542X, have been found in 66 Jewish CF
      patients. The average frequency of the delta F508 mutation in the Jewish
      population is 33.8%. The G542X mutation accounts for 13% of the Ashkenazi CF
      mutations and has been found in three out of seven chromosomes of Jewish patients
      from Turkey (probably descended from Ashkenazi immigrants). The G542X mutation
      was not found in any of the other non-Ashkenazi patients. All the G542X bearing
      chromosomes have the same haplotype. Based on these observations it is concluded
      that the G542X mutation was introduced into the Jewish people after the split
      into Ashkenazi and non-Ashkenazi.

PMID- 1377278
TI  - Analysis of the chicken fast myosin heavy chain family. Localization of isoform
      specific antibody epitopes and regions of divergence.
AB  - cDNAs encoding the rod region of four different fast myosin heavy chains (MYCHs)
      in the chicken were identified, using anti-MYCH monoclonal antibodies, in two
      expression libraries prepared from 19-day embryonic and adult chicken muscle.
      These clones were used to determine the amino acid sequences that encompass the
      epitopes of five anti-MYHC monoclonal antibodies. Additionally, the amino acid
      sequences were compared to each other and to a full length embryonic MYHC.
      Although there is extensive homology in the chicken fast myosin rods, sequences
      within the hinge, within the central portion of the light meromyosin fragment,
      and at the carboxy terminus exhibit the largest number of amino acid
      substitutions. We propose that divergence within these subdomains may contribute
      to isoform-specific properties associated with skeletal myosin rods.

PMID- 1377281
TI  - Substance P immunoreactivity of rat brain stem neurons in primary culture.
AB  - Substance P (SP)-ergic neurons from 16/17 day-embryonic rat brain stem in primary
      culture were identified by immunocytochemistry using biotinylated avidin and
      phosphatase alkaline methods with affinity-purified anti-SP antibodies. An
      average of 84% of neurons contained SP from day 9 to day 21 after plating. These
      in vitro data show that SP-containing neurons develop in our culture conditions.
      SP may act as a maturation factor as well as a neurotransmitter.

PMID- 1377279
TI  - Promoter sequence containing (CT)n.(GA)n repeats is critical for the formation of
      the DNase I hypersensitive sites in the Drosophila hsp26 gene.
AB  - We have analyzed P-element-transformed lines carrying hsp26/lacZ transgenes with
      various deletions and substitutions within the Drosophila melanogaster hsp26
      promoter region in order to identify the sequences required for the formation of
      the DNase I hypersensitive sites (DH sites). DH sites are generally found
      associated with promoters and enhancer elements of active and inducible
      eukaryotic genes, and are thought to be nucleosome-free regions of DNA that
      interact with regulatory proteins and the transcriptional machinery. There are
      two major DH sites located within the promoter region of the hsp26 gene, centered
      at -50 and at -350 (relative to the hsp26 transcription start site). The
      sequences from -135 to -85, which contain (CT)n.(GA)n repeats, contribute
      significantly to the formation of the DH sites in the hsp26 promoter region.
      Deletion or substitution of this (CT)n region drastically reduces the
      accessibility of the DNA at these sites to DNase I. This reduction in
      accessibility was quantified by measuring the susceptibility of the DNA within
      nuclei to cleavage at a restriction site within the DH site. In addition to the
      (CT)n region and the promoter at -85 to +11 (region P), one of two other regions
      must be present for effective creation of the DH sites: sequences between -351
      and -135 (region A), or sequences between +11 and +632 (region D). Disruption of
      the wild-type chromatin structure, as assayed by the loss of accessibility to the
      DH sites, is correlated with a decrease in inducible transcriptional activity,
      even when the TATA box and heat shock regulatory elements are present in their
      normal positions.

PMID- 1377280
TI  - Structure, expression, and function of Ng-CAM, a member of the immunoglobulin
      superfamily involved in neuron-neuron and neuron-glia adhesion.
AB  - The neuron-glia cell adhesion molecule (Ng-CAM) mediates neuron-neuron adhesion
      by a homophilic mechanism and neuron-astrocyte adhesion by a heterophilic
      mechanism. The protein is expressed on neurons and Schwann cells but not on
      astrocytes. It is most prevalent during development on cell bodies of migrating
      neurons and on axons during formation of nerves. Ng-CAM expression is greatly
      increased following nerve injury. Anti-Ng-CAM antibodies inhibited migration of
      granule cells along Bergmann glia in cerebellar explants and fasciculation of
      neurites in outgrowths from explants of dorsal root ganglia. The combined results
      indicate that Ng-CAM on neurons binds to Ng-CAM on adjacent neurons and to as yet
      unidentified ligands on astrocytes. Ng-CAM is synthesized in chicken neurons from
      a 6 kb mRNA as Mr approximately 200,000 forms which are cleaved to yield two
      components of Mr 135,000 and 80,000. It is glycosylated and can be
      phosphorylated. Amino acid sequence analysis indicates that it contains six
      immunoglobulin domains, five fibronectin type III repeats, a transmembrane domain
      and a cytoplasmic region. Structural analyses indicate that Ng-CAM is most
      closely related to the mammalian glycoprotein L1 but significant differences
      between them strongly suggest that they are not equivalent molecules. The recent
      identification of another structurally related molecule in the chicken called Nr
      CAM underscores the notion that these molecules are members of a subfamily of
      neural cell adhesion molecules within the immunoglobulin superfamily that have
      related or complementary functions in the nervous system.

PMID- 1377282
TI  - Preparation of a protein-free total brain white matter lipid fraction:
      characterization of liposomes.
AB  - A method of preparing a total lipid extract (TLE), free of protein, by extracting
      brain white matter with tetrahydrofuran is presented. The optimal conditions of
      extraction were found to be 50 ml of THF per gram of lyophilized tissue, though
      fresh tissue can also be used if larger volumes of solvent are employed. The
      method allowed, in a short time and in a single step, a yield of TLE of 50% on a
      dry weight basis. Its analytical characterization revealed a qualitative and
      quantitative composition very similar to the lipid composition of CNS myelin,
      including all the phospholipid and galactolipid species, cholesterol and
      gangliosides, but it contained only traces (0.1%) of protein. TLE has been used
      to prepare liposomes, either multilamellar (MLVs) or unilamellar (LUVs, SUVs),
      characterized by freeze-fracture electron microscopy. A multilayered,
      heterogeneous population of liposomes is observed in the MLVs preparation. When
      these samples were submitted to a freezing and thawing procedure the resulting
      liposomes were single-walled, and their intravesicular volume was increased. They
      were quite impermeable to the monovalent cation 86Rb+ and, by contrast, rather
      permeable to 45Ca+ +. Their complex lipid composition, together with their
      permeability properties and their response to ionophores, make them very useful
      to study protein-lipid interactions occurring within the myelin membrane as well
      as the functional properties of myelin proteins in reconstitution experiments.

PMID- 1377283
TI  - Expression of the neu oncogene under the transcriptional control of the myelin
      basic protein gene in transgenic mice: generation of transformed glial cells.
AB  - We have taken a transgenic approach in an effort to specifically transform
      oligodendrocytes, the myelinating glial cells of the central nervous system
      (CNS). Transgenic mice were generated with a DNA construct that contained the
      activated neu oncogene under the transcriptional control of the myelin basic
      protein (MBP) gene. The MBP/c-neu transgenic animals have experienced a low
      incidence of brain tumors that express molecular markers specific to
      oligodendrocytes, providing a mouse model to study the formation and progression
      of oligodendrocyte tumors. A tumor from a transgenic animal has been dispersed in
      culture, and transformed cells that express properties of oligodendrocytes and
      astrocytes have been maintained. The degree to which these cells express
      phenotypic characteristic of oligodendrocytes or astrocytes is influenced by
      culture conditions. These transformed cells should serve as a valuable resource
      with which to study various molecular and biochemical aspects of the myelination
      process, as well as the lineage interrelationship of CNS glial cells.

PMID- 1377284
TI  - Effect of dexamethasone on the nerve growth factor-induced increase in the NILE
      glycoprotein in PC12 cells.
AB  - The long-known and well-documented increase in the NILE glycoprotein produced by
      nerve growth factor in PC12 cells is prevented by simultaneous treatment with
      dexamethasone. The absence of this surface marker on the fully differentiated
      cells has been demonstrated by both glucosamine incorporation and
      immunohistofluorescence.

PMID- 1377285
TI  - Cellular immune crossreactivity between myelin basic protein and synapsin in rats
      with experimental allergic encephalomyelitis.
AB  - We previously demonstrated that antibodies against myelin basic protein (MBP)
      obtained from animals with experimental allergic encephalomyelitis (EAE), induced
      with MBP and purified by affinity chromatography, have the property to recognize
      a neuronal protein, synapsin Ia and Ib. To investigate whether this
      crossreactivity also occurs at the cellular level, we purified spleen and lymph
      node mononuclear cells from rats sensitized with MBP or synapsin using
      polystyrene plates coated with the respective antigen. We observed that animals
      injected with MBP have T lymphocytes that bind both antigens. Using the same
      system, each purified cell population was confronted again to the studied
      antigens. The anti-MBP cells recognized once more epitopes of MBP and about 40%
      of them also recognized synapsin. On the other hand, cells that first were
      attached to synapsin, in the second exposure to antigens bound to MBP and
      synapsin in similar amounts. Double immunofluorescent labeling of the mononuclear
      cells isolated from animals injected with bovine myelin or MBP showed that the
      same lymphocyte was able to recognize MBP as well as synapsin. In both
      experimental systems the quantitative results were similar indicating that in
      bovine myelin- or MBP-sensitized animals practically all the cells that recognize
      synapsin are anti-MBP cells, and of the total cells raised against MBP, around
      40% of them show this crossreactivity. On the contrary, animals injected with
      synapsin have cells that bind to this protein but not to MBP indicating that the
      described crossreactivity, as observed at humoral level, is only in one
      way.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377286
TI  - Effects of hypertonic saline dextran resuscitation on oxygen delivery, oxygen
      consumption, and lipid peroxidation after burn injury.
AB  - We compared the effects of lactated Ringer's (LR) and hypertonic saline dextran
      (HSD) on postburn cardiovascular function, O2 consumption, lipid peroxidation,
      and bacterial translocation. Miniature pigs with 40% total body surface area
      (TBSA), third-degree burns received, 30 minutes postburn, either Parkland
      resuscitation (LR group, n = 8) or HSD, 10 mL/kg/30 minutes, followed by LR, 4
      mL/kg/%burn over the next 23 hours (HSD group, n = 8). The HSD prevented the
      early decrease in cardiac index (CI); the early increase in the resistance of the
      systemic, mesenteric, celiac, and renal vascular beds; and the decrease in
      mesenteric O2 consumption seen after burns when LR alone is used for
      resuscitation. The HSD also moderated the systemic and mesenteric lipid
      peroxidation. Bacterial translocation was less in the HSD group (3 of 8 animals)
      compared with the LR group (5 of 8 animals), but was not statistically different.
      Hypertonic saline dextran may be beneficial in improving the postburn
      microcirculation and attenuating postburn oxidant-induced lipid peroxidation in
      the systemic tissues and the gut.

PMID- 1377287
TI  - Improved indication and followup in transurethral resection of the prostate using
      the computer program CLIM: a prospective study.
AB  - Analysis of preoperative and postoperative detrusor pressure-flow measurements
      with the aid of the IBM compatible software package CLIM in 29 patients who
      underwent transurethral prostatic resection indicated that CLIM supplies reliable
      obstruction parameters that are recommended for preoperative assessment and
      postoperative followup, and that approximately a third of the patients who
      present with prostatism are nonobstructed, suggesting that the indication for
      transurethral resection of the prostate is over assessed.

PMID- 1377288
TI  - Prevention of acrolein-induced bladder injury by pentosanpolysulfate.
AB  - The active metabolite of cyclophosphamide, acrolein, which is capable of damaging
      the transitional epithelium of the bladder, was evaluated in both in vivo and in
      vitro models to determine if its damaging effect could be reduced by the presence
      of a sulfated polysaccharide pentosampolysulfate. It was discovered that in all
      models pentosanpolysulfate was capable of reducing transitional cell injury due
      to acrolein.

PMID- 1377289
TI  - False positive prostate specific antigen values in the sera of women with renal
      cell carcinoma.
AB  - The assessment of serum prostate specific antigen (PSA) with a polyclonal
      radioimmunoassay in 22 women with renal cell carcinoma resulted in measurable
      values in 6 patients, with the values ranging from 0.5 to 27.0 ng./ml. Tumor
      stage was T3 in all of these patients and the morphological features showed an
      eosinophilic subtype according to the German nomenclature. Additional
      measurements with a monoclonal radioimmunoassay in 3 of these 6 patients were
      negative as were all subsequent measurements postoperatively, although performed
      with the polyclonal radioimmunoassay. Immunohistochemical staining was negative
      for PSA. However, positivity for alpha-1-antichymotrypsin was detected, which was
      reported to occur in complexes with PSA and other proteases. Cross reaction
      between the polyclonal antibodies of the radioimmunoassay and 1 of these
      complexes is concluded. As far as clinical considerations are concerned, such
      cross reaction must be considered just as likely in male patients. Thus, it is
      recommended that therapeutic considerations in patients who underwent radical
      prostatectomy, for example, should not be exclusively based on PSA measurement
      performed with a polyclonal assay.

PMID- 1377290
TI  - The effect of digital rectal examination on the serum prostate specific antigen
      concentration: results of a randomized study.
AB  - To determine the effect of digital rectal examination on the serum prostate
      specific antigen (PSA) concentration a prospective, randomized, controlled trial
      involving 143 patients was conducted. Of the patients 86 (60%) had benign
      prostatic hyperplasia (BPH), 47 (33%) had prostate cancer and 10 (7%) had chronic
      prostatitis. The study group consisted of 71 men, all of whom had a serum PSA
      determination followed by a digital rectal examination and then a second serum
      PSA determination. The control cohort consisted of 72 men, all of whom had 2
      serum PSA determinations without an intervening digital rectal examination. The
      median change in the serum PSA level for the study group was 0.4 ng./ml. compared
      to -0.1 ng./ml. for the control cohort (p less than 0.0001). For 76% of the study
      patients the second serum PSA level was greater than the initial value; only 32%
      of the control patients exhibited a higher second serum PSA level than the
      initial level (p less than 0.0001). However, only 4 patients with an initial PSA
      value in the reference range (0.0 to 4.0 ng./ml.) had a post-digital rectal
      examination value greater than 4.0 ng./ml. and only 1 patient whose presenting
      serum value was less than 10.0 ng./ml. had a serum PSA level greater than this
      cutoff point after digital rectal examination. This minimal change in serum PSA
      after digital rectal examination was independent of the diagnosis (BPH, cancer or
      chronic prostatitis), initial serum PSA concentration and examiner. Thus,
      although digital rectal examination had a statistically significant effect on the
      serum PSA concentration, the clinical significance of a 0.4 ng./ml. median
      increase appears inconsequential. Based on these findings, physicians should be
      confident that the serum PSA concentration in the immediate post-digital rectal
      examination period is accurate and does not compromise clinical use of the tumor
      marker.

PMID- 1377291
TI  - [Anti-platelet antibody and platelet function].
AB  - The effect of anti-platelet antibodies, including murine monoclonal antibodies,
      autoantibodies and alloantibodies, on platelet function was analyzed. The target
      antigen of these antiplatelet antibodies, investigated in the present study, was
      a glycoprotein IIb/IIIa, which is a receptor of fibrinogen and plays an important
      role in platelet aggregation. Some of these antibodies inhibited agonist-induced
      platelet aggregation. The target antigen of one murine monoclonal antibodies,
      designated OP-G2, was a glycoprotein IIb/IIIa and interestingly, this antibody
      induced platelet aggregation, which required divalent cation and fibrinogen. We
      compared the epitope of these antibodies by inhibition assay and found the
      epitope of these antibodies to be very close. The binding of OP-G2 to the
      platelets required Ca2+. These data suggest that OP-G2 recognizes an epitope at
      or in very close proximity to the fibrinogen binding site of GPIIb/IIIa, as
      compared with other antibodies.

PMID- 1377292
TI  - [Regulation of nitric oxide synthase].
AB  - Nitric oxide (NO) synthase is known to be widely distributed in various cells. We
      characterized this enzyme using partially purified enzyme fractions from rat
      neutrophils, macrophages, and cerebellum. The cerebellar fraction required Ca(2+)
      calmodulin, while that from macrophages required neither calmodulin nor Ca2+. The
      neutrophil fraction required Ca2+. The enzyme was inhibited by analogues of the
      substrate, L-arginine. N omega-nitro-L-arginine (NNA) was 20 times more potent
      than L-NG-monomethyl-arginine (NMA) in blocking the cerebellar enzyme. In
      contrast, NNA and NMA were about equipotent against neutrophil and macrophage
      enzymes. These data suggest that the enzyme is regulated by 3 different
      mechanisms in these cells, with differences between the cerebellar and neutrophil
      or macrophage enzyme in the catalytic binding site.

PMID- 1377293
TI  - [Detection of circulating activated platelets by anti-GMP-140 monoclonal
      antibodies].
AB  - The clinical significance and detection methods for circulating activated
      platelets are reviewed. It has been recently demonstrated that three kinds of
      platelet granules, dense granule, alpha-granule and lysosome, have specific
      membrane proteins; granulophysin, GMP-140 (PADGEM) and CD63 antigen,
      respectively, and that these specific granule-membrane proteins become exposed on
      the surface of the activated platelets. It is believed that detection of
      circulating activated platelets, using monoclonal antibodies specific to these
      granule-membrane, may be reliable and diagnostic value in thrombotic and
      prethrombotic diseases. Preliminary clinical studies using 2T60, a newly
      developed anti-GMP-140 monoclonal antibody, was presented.

PMID- 1377294
TI  - [Polytopical ectopic rhythms].

PMID- 1377295
TI  - Protective effects of calcium antagonists in human renal transplantation.
AB  - To test the hypothesis that calcium antagonists decrease the incidence and
      severity of delayed graft function, we conducted three separate, prospective,
      randomized trials. In these trials, we investigated the effects of diltiazem and
      those of the prostacyclin analogue iloprost. In the first study, 22 control
      patients and 20 diltiazem patients received grafts perfused with either vehicle
      or diltiazem 20 mg/liter in the Euro-Collins solution. Subsequently, the
      diltiazem subjects were given the drug as a bolus of 0.28 mg/kg, followed by a
      continuous infusion of 0.002 mg/min/kg for the following two days. Thereafter,
      diltiazem 60 mg was given to the treated subjects orally for up to four years. In
      the second study, 11 control subjects and 10 diltiazem subjects received the same
      postoperative regimen, but all grafts were harvested without addition of
      diltiazem to the perfusion solution. In the third protocol, four groups were
      studied as follows: 19 control subjects who received no specific treatment, 16
      subjects who received diltiazem, 16 subjects who were given iloprost, and 14
      subjects who received both iloprost and diltiazem. The donor kidney of treated
      patients was perfused with either diltiazem, iloprost, or both drugs. Primary
      graft function occurred more commonly in the groups receiving diltiazem. Further,
      in the first study the number of hemodialyses per patient was reduced in those
      patients with delayed graft function. Fewer rejection episodes occurred in
      patients receiving diltiazem. Plasma levels of soluble interleukin-2 receptors
      decreased significantly during diltiazem treatment. Moreover, renal biopsies
      showed less severe signs of Cyclosporin A (CsA) nephrotoxicity in diltiazem
      treated patients compared to controls, even though these patients also exhibited
      higher CsA trough levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377296
TI  - [Loss of ganglion cells in the retina secondary to vincristine therapy].
AB  - We report the case of a 25-year-old black female from Zaire with AIDS diagnosed 2
      years earlier. Nine months before her death, she was treated for a disseminated
      Kaposi sarcoma with vincristin, adryamycin and bleomycin. At that time, visual
      acuity was normal and ophthalmologic examination was unremarkable except for the
      presence of bilateral Drusen and a cotton wool spot OS. Three months after the
      onset of chemotherapy, the patient complained of progressive visual field
      constriction, which progressed to blindness within a 4 month period. Five months
      after the onset of the tri-therapy a bilateral CMV retinitis developed, which was
      successfully treated by intravitreous injections of ganciclovir. This therapy was
      stopped as soon as blindness was established, with subsequent massive bilateral
      recurrence of the CMV retinitis. Histologic examination showed complete atrophy
      of the retinal ganglion cells and areas of CMV retinitis. The optic nerve was
      demyelinated and exhibited astrocytic gliosis. Immunohistochemistry confirmed the
      presence of CMV in infected retina and revealed the absence in the optic nerve of
      the class III beta-tubulin isotype and of the 200 kd neurofilament subunit. In
      contrast, oculomotor nerves appeared intact. The presence of HIV in the eye and
      in the optic nerve was excluded using PCR technique. The retinal ganglion cell
      loss and optic nerve atrophy appeared to be purely degenerative in nature, since
      there was no evidence of vascular occlusion, inflammation or retrobulbar
      compressive process. We therefore conclude that blindness was caused by
      vincristine therapy. The patient actually received 22 mg of vincristin
      intravenously in 11 courses over 7 months, although discontinuation was
      recommended by us after 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377297
TI  - Atherosclerosis, cell motility, calcium, and calcium-channel blockers.
AB  - Three key players in the humoral-cellular interactions that occur during the
      early development of atherosclerosis are presented as they activate platelets and
      vascular smooth muscle cells but eventually can be corrected by calcium-channel
      blockers. Platelet-activating factors via phospholipase C and phosphoinositides
      increase cytosolic calcium and phosphorylate contractile proteins, thereby
      inducing a change--aggregation and the secretory response of platelets. Low
      density lipoprotein (LDL) has a similar hormone-like action and activates the
      signal transfer cascade that eventually leads to platelet aggregation as well as
      vascular smooth muscle cell proliferation. These effects can be greatly reduced
      by high-density lipoproteins. Platelet-derived growth factor stimulates the
      transcription of the LDL-receptor gene as well as the HMG-CoA reductase gene. The
      latter is inhibited by calcium-channel antagonists while the former is further
      enhanced. Thus, calcium-channel antagonists interfere with the stimulus-response
      coupling not only via slow calcium-channel influx inhibition but also by an
      additional membrane action and interference with gene activation.

PMID- 1377298
TI  - Calcium, calcium antagonism, and structural changes in hypertension. Satellite
      symposium to the 5th ESH meeting. Milan, June 7, 1991.

PMID- 1377299
TI  - Calcium, calcium antagonism, atherosclerosis, and ischemia.
AB  - Calcium is a ubiquitous cation involved in a wide variety of physiological
      processes. Normally, cytosolic calcium is maintained within narrow limits but
      under certain conditions the levels rise--either because of excess calcium entry,
      internal release, or failure of the extrusion mechanisms. Such conditions include
      hypertension and myocardial ischemia. Calcium ions are also involved in the
      formation of atherosclerotic lesions. Hypertension, ischemic heart disease, and
      atherosclerosis are all amenable to calcium antagonist therapy. The efficacy of
      this class of drugs in the management of such a wide spectrum of disorders is in
      accord with the central role played by calcium in the etiology of these
      disorders. To some extent, however, the disorders are interrelated, with
      hypertension being a major risk factors for ischemic heart disease and
      atherosclerosis.

PMID- 1377300
TI  - The development and regression of vascular hypertrophy.
AB  - Genetic hypertension [essential hypertension (EH) in humans and spontaneous
      hypertension in rats (SHRs)] is associated with an altered vascular structure,
      expressed in resistance vessels (small arteries) as an increased media:lumen
      ratio. The vascular smooth muscle cells appear normal and there is no cellular
      hypertrophy. The amount of smooth muscle may be increased in SHR resistance
      vessels (i.e., there is evidence for hyperplasia). Present evidence in EH
      indicates that there is no increase in vascular smooth muscle mass, suggesting
      that the altered structure is due to "remodeling," a rearrangement of a normal
      amount of normal material. With antihypertensive therapy, reduction in mean blood
      pressure does not necessarily normalize vascular structure, and there are few
      grounds for supposing that one drug is better than another in this respect.
      Preliminary evidence suggests that normalization of the pulse pressure may be
      more important than normalizing mean blood pressure, if vascular structure is to
      be corrected. Although vascular structure may not per se be an important
      determinant of blood pressure, reduction in blood pressure without correcting
      vascular structure is undesirable. Thus, improvement of the means for correcting
      vascular structure may be an important way of improving prognosis with
      antihypertensive treatment.

PMID- 1377301
TI  - Effects of nifedipine-GITS on left ventricular mass and left ventricular filling.
AB  - Sixteen patients with initial diastolic blood pressure greater than or equal to
      120 mm Hg were treated for 1 year with extended-release nifedipine [nifedipine
      GITS (gastrointestinal therapeutic system)]. Serial changes in left ventricular
      mass index and associated alterations in left ventricular systolic function, left
      ventricular filling, plasma renin activity, atrial natriuretic peptide, and
      catecholamines were evaluated. Blood pressure was significantly reduced from 200
      +/- 8/122 +/- 3 mm Hg (mean +/- SEM) to 144 +/- 5/89 +/- 2 mm Hg (p less than
      0.0001) at 1 year. Eleven patients (69%) required only nifedipine-GITS for blood
      pressure control and 5 (31%) required the addition of chlorthalidone. After 6
      months, the left ventricular mass index was significantly reduced by 19% from 121
      +/- 8 to 96 +/- 7 g/m2 and this reduction was sustained at 1 year. Septal and
      posterior wall thicknesses were reduced from 13.4 +/- 0.1 to 11.2 +/- 0.04 mm and
      from 12.8 +/- 0.1 to 10.0 +/- 0.03 mm (p less than 0.001), respectively.
      Prevalence of left ventricular hypertrophy decreased from 63 to 25%. Left
      ventricular fractional shortening increased from 34 to 42% (p less than 0.05) and
      the relationship between fractional shortening and end-systolic stress did not
      change. Over the year of sustained blood pressure reduction, the peak velocity of
      early filling increased from 58 to 63 cm/s (p = 0.07), the peak velocity of late
      filling did not change, and the ratio of late to early peak velocity of left
      ventricular filling significantly decreased (p less than 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377302
TI  - Nitrendipine in the therapeutic management of elderly hypertensive patients:
      results of a multicenter trial. Andalousian Hypertension Group.
AB  - Two hundred forty-seven [142 women (57.49%)] elderly patients with essential
      hypertension (diastolic blood pressure between 95 and 114 mm Hg) and an average
      age of 67.4 +/- 6 years were included in an open multicenter ambulatory trial.
      One hundred thirty-seven had some kind of associated disease. After a 15-day
      washout period, the patients began nitrendipine therapy (10 mg o.d.). After 1
      month, the dose was increased to 20 mg o.d. in patients with diastolic blood
      pressure (DPB) greater than or equal to 95 mm Hg, and thereafter 5 and 10 mg o.d.
      of bisoprolol was added to the maximal dose of nitrendipine (20 mg o.d.) in the
      case of patients with DBP greater than or equal to 95 mm Hg at the end of the
      second and third months, respectively. At the end of the 6-month follow-up
      period, the systolic and diastolic pressures had dropped -35 and -21 mm Hg,
      respectively, without any change in heart rate or Quetelet index. In 210 patients
      (84.9%), blood pressure control was achieved: 26 (10.5%) with 10 mg of
      nitrendipine, 149 (60.3%) with 20 mg of nitrendipine, and 35 (14.1%) by adding
      bisoprolol. The lipid profile, glucose, potassium, uric acid, or creatinine did
      not change negatively. Sixty-six (26.72%) patients reported clinical side
      effects, although these were mild; only 15 (6.07%) patients were excluded because
      of side effects. Nitrendipine has been shown to have a high therapeutic efficacy
      and biochemical tolerance for first-line treatment of elderly patients with mild
      to-moderate essential hypertension with or without associated diseases.

PMID- 1377303
TI  - Antihypertensive and metabolic effects of nitrendipine in non-insulin-dependent
      diabetes mellitus with hypertension.
AB  - Fifteen non-insulin-dependent diabetes mellitus hypertensive patients received
      nitrendipine (20-40 mg) for 24 weeks. Mean systolic and diastolic blood pressure
      decreased significantly from 177/102 mm Hg before treatment to 153/86 mm Hg (p
      less than 0.001) after treatment. Meanwhile, the heart rate, body weight, indices
      of glycemic control (glucose, glycosylated hemoglobin, fructosamine, and serum C
      peptide levels), and serum lipid fractions did not change. It is concluded that
      nitrendipine does not impair glucose and lipid metabolism in diabetic patients
      while exerting its antihypertensive effect.

PMID- 1377304
TI  - Oxidized low-density lipoproteins in atherogenesis: possible mechanisms of
      action.
AB  - The increased atherogenic potential of oxidized low-density lipoprotein (ox-LDL)
      is well documented. In the present study, we investigated possible mechanisms of
      action of the difference to native LDL. In vitro oxidation of LDL was determined
      by measurement of thiobarbituric acid-reacting substances and absorption at 234
      nm. Copper (5 mumol/L) induced significant (p less than 0.01) oxidation in vitro.
      Furthermore, LDL isolated from atherosclerotic patients was slightly but
      significantly (p less than 0.05) more oxidized than LDL from normal controls
      (2.81 +/- 0.08 vs. 3.21 +/- 0.16 nmol of TBARS/mg of LDL protein). Ox-LDL caused
      significantly (p less than 0.01) more pronounced contractions of rat aortic rings
      in vitro compared to nonoxidized LDL expressed as a percentage of maximal
      contractions induced by 40 mmol/L of KCl (29.0 +/- 5.4% vs. 61.1 +/- 7.2%).
      Lysolecithin, which is a principal component of ox-LDL formed during oxidation,
      induced a dose-dependent increase in intracellular free calcium in vascular
      smooth muscle cells cultured from rat aorta. Doses from 2-25 micrograms/ml were
      tested and caused a maximum increase of more than 500% (25 micrograms/ml). In
      conclusion, this study provides further evidence for a higher biological activity
      of ox-LDL. Lysolecithin might be one of the active components formed during
      oxidation of LDL.

PMID- 1377305
TI  - Use of a microprocessor-equipped tablet box in monitoring compliance with
      antihypertensive treatment.
AB  - Compliance with antihypertensive therapy is usually monitored by questionnaire,
      tablet counts, or estimation of drug levels in blood or in urine. The aim of this
      study was to examine patient compliance by means of an "electronic monitor."
      After 2 weeks of run-in on placebo, 34 moderately hypertensive patients were
      included in an open, randomized, crossover trial examining the efficacy and
      tolerance of nitrendipine, 20 mg as a single daily dose (morning or evening) for
      1 month. We analyzed the results in 26 patients. Patients were supplied with
      tablet boxes equipped with a microprocessor (MENS) that registered the timing and
      duration of opening of the box over both the placebo and nitrendipine periods.
      Compliance (%) was calculated as the ratio of the number of days that the pill
      box was opened to the number of days between visits. The compliance was analyzed
      for each treatment group, namely placebo and nitrendipine morning and evening,
      over 1 month. Compliance (mean + SD) was 96.5 +/- 7.4% on placebo and 94.4 +/-
      10.7% in the morning and 90.6 +/- 15.4% in the evening. Nitrendipine was taken in
      the morning at 0700 h +/- 2 h and in the evening at 1859 h +/- 2 h 12 min. The
      frequency of 24 h +/- 1 h intervals between medication was 83.5% on placebo. This
      frequency was 72.6% for morning dosage and 71.8% for evening dosage on
      nitrendipine. There were no differences in compliance between the morning and
      evening groups when analyzed according to age and sex. There was a negative
      correlation with time (r = -0.57, p less than 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377307
TI  - Effects of slow-release verapamil and nitrendipine on office and 24-hour
      ambulatory blood pressure in hypertensive patients.
AB  - The aim of the present study was to compare the effects of slow-release verapamil
      (V), 240 mg and nitrendipine (N), 20 mg, administered once daily, on office (OBP)
      and 24-h ambulatory blood pressure (ABP) in patients with mild-to-moderate
      hypertension. Twenty patients were entered into this open, randomized, two-group
      (V, N) parallel study. The study groups had similar age and sex distribution. The
      OBP (V, 155/103 +/- 19/8 mm Hg; N, 141/98 +/- 13/4 mm Hg), heart rate (HR) (V, 74
      +/- 7 beats/min; N, 77 +/- 10 beats/min), daytime systolic ABP (V, 149 +/- 14 mm
      Hg; N, 147 +/- 13 mm Hg), and nighttime ABP of the two groups were not
      statistically different after a 2-week washout period. The daytime diastolic ABP
      (V, 99 +/- 6 mm Hg; N, 93 +/- 6 mm Hg) was slightly lower (p less than 0.05) in
      group N. Both the OBP (V, 136/90 +/- 19/9 mm Hg; N, 135/85 +/- 10/4 mm Hg) and
      daytime ABP (V, 132/85 +/- 14/4 mm Hg; N, 136/87 +/- 13/8 mm Hg) dropped in the
      two groups after 8 weeks of treatment. Nonparametric analysis did not show
      statistical differences between the groups in OBP and ABP percentage drop. There
      was no significant change in nighttime ABP, HR (V, 73 +/- 10 beats/min; N, 74 +/-
      12 beats/min), ECG, and laboratory exams. We conclude that both verapamil SR and
      nitrendipine are effective in reducing blood pressure in hypertensive patients
      without altering the HR.

PMID- 1377306
TI  - Acute and chronic nitrendipine administration in essential hypertension: a
      chronobiologic study.
AB  - To evaluate the chronobiologic pattern of the hypotensive effect of nitrendipine,
      10 patients with mild-to-moderate arterial hypertension were studied. They
      received a randomized single dose (20 mg) of nitrendipine and placebo, and 20 mg
      of nitrendipine daily for 2 months. Systolic and diastolic blood pressure (SBP
      and DBP, respectively) and heart rate (HR) were measured for 24 h using an
      automatic noninvasive device. The data were analyzed by single and mean cosinor
      methods and by ANOVA and Student's paired t test. Chronic administration of
      nitrendipine resulted in a more effective lowering of the SBP and DBP mesor,
      compared with placebo and acute administration, preserving the circadian rhythms.
      The preservation of the HR circadian rhythm agrees with the lack of interference
      of the drug with neurohormonal mechanisms.

PMID- 1377308
TI  - Metabolic and antihypertensive effects of nifedipine in hypertensive patients.
AB  - We studied the effects of nifedipine on blood pressure and on clinical and
      analytical parameters in hypertensive patients. Seven male and eight female
      subjects (mean age of 46.27 +/- 5.38 years, range of 41-56 years) with essential
      arterial hypertension were given nifedipine (20 mg b.i.d.) for 3 months. Before
      and after treatment, history, blood pressure, and biochemical values were
      recorded [blood: Na, K, Ca, creatinine, uric acid, triglycerides, cholesterol,
      HDL cholesterol, antidiuretic hormone (ADH), and aldosterone; urine: Na, K, Ca,
      creatinine, ADH, aldosterone, and percentage fraction of Na, K, and Ca excreted].
      After 3 months of treatment, we found (a) significant decreases in systolic (147
      +/- 18 vs. 166 +/- 16 mm Hg, p less than 0.001) and diastolic blood pressure (90
      +/- 8 vs. 107 +/- 8 mm Hg, p less than 0.0007), triglycerides (107 +/- 47 vs. 120
      +/- 49 mg/dl, p less than 0.0007), and cholesterol (236 +/- 4 vs. 257 +/- 44
      mg/dl, p less than 0.00075) in blood, and in K excretion (50 +/- 19 vs. 46 +/- 19
      mEq/g of creatinine, p less than 0.0007) and excreted fraction of K (49 +/- 6%
      vs. 8 +/- 5%, p less than 0.0012) in urine; (b) significant increases in HDL
      cholesterol (65 +/- 13 vs. 58 +/- 13 mg/dl, p less than 0.001) in blood, and in
      Na (115 +/- 73 vs. 109 +/- 69 mEq/g of creatinine, p less than 0.0007) in urine;
      and (c) no significant change in the remaining biochemical parameters, or in
      heart rate. Secondary effects included flushing (34%), headache (20%), ankle
      swelling (17%), dizziness (13%), palpitations (4%), and pruritus (4%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377309
TI  - Action of metoprolol, enalapril, diltiazem, verapamil, and nifedipine on cell
      growth of vascular smooth muscle cells.
AB  - The influence of nifedipine, verapamil, diltiazem, metoprolol, and enalapril on
      the basal and angiotensin II (Ang II)-induced elevation of [3H]thymidine
      incorporation into vascular smooth muscle cell (VSMC) DNA was examined. Our
      results from four independent experiments, each performed in triplicate, are
      summarized by calculating the half-maximal inhibitory concentration (IC50) of the
      drugs. Nifedipine, verapamil, and diltiazem had IC50 values of 2.3 +/- 0.7 x 10(
      6), 3.5 +/- 0.3 x 10(-6), and 6.6 +/- 2.8 x 10(-6) M, respectively. Metoprolol
      had an IC50 value of 49 +/- 16 x 10(-6) M, whereas enalapril was completely
      ineffective. All drugs used had no influence on the basal cell [3H]thymidine
      incorporation. This in vitro study allows one to conclude that the calcium-entry
      blockers can inhibit the Ang II-induced cell growth and thus may have beneficial
      effects on the development and regression of vascular growth, which is associated
      with the pathogenesis of cardiovascular diseases.

PMID- 1377310
TI  - Calcium antagonists and vascular smooth muscle cells in atherogenesis.
AB  - Vascular smooth muscle cells (SMCs) play a key role in the development of
      atherosclerotic lesions. Vascular smooth muscle, however, does not represent a
      homogeneous tissue. Using myosin as a marker of the differentiation processes in
      development and in vascular disease, we have been able to demonstrate the
      existence of distinct SMC populations in rabbit aorta. In our studies, a specific
      SMC population of the aortic media showing an "immature" type of myosin isoform
      expression accounted for the majority of SMCs present in the atherosclerotic
      plaque. Nifedipine, a dihydropyridine-derived calcium antagonist, was able to
      decrease the size of this particular SMC population and to prevent the
      development of atherosclerotic lesions in hypercholesterolemic rabbits. Here we
      report about a similar effect obtained by treating hypercholesterolemic rabbits
      with nitrendipine, another dihydropyridine-derived calcium antagonist. This
      article also summarizes the main experimental and clinical studies conducted on
      the antiatherogenic effect of calcium antagonists and focuses on the mechanisms
      underlying this effect, particularly at the vascular SMC level.

PMID- 1377311
TI  - Prospective randomized clinical trial comparing brachytherapy and laser
      photoablation for palliation of esophageal cancer.
AB  - Twenty-three consecutive patients with advanced esophageal cancer were randomized
      to receive either endoluminal irradiation or laser photoablation treatment.
      Initial improvement in dysphagia scores was observed in 83% (brachytherapy) and
      91% (laser). This improvement in dysphagia was maintained at 2 months in 75%
      (brachytherapy) and 81% (laser). Performance scores improved in 33%
      (brachytherapy) and 36% (laser). Both treatments were well tolerated, required a
      minimum of inpatient treatment time, and allowed patients to die without terminal
      admission to district referral centers. Retreatments were three times as common
      with laser therapy, but the frequency of treatment failures was equal. Minor
      complications, especially transient early dysphagia, was more common in the
      brachytherapy group, although the only major complication (perforation) occurred
      in the laser group. No procedure-related deaths occurred in either group.

PMID- 1377313
TI  - Current approach to hypoplastic left heart syndrome. Palliation, transplantation,
      or both?
AB  - Over the past 3 years, 35 newborn infants have been referred for surgical
      management of hypoplastic left heart syndrome. Surgical palliation (first-stage
      Norwood) or cardiac transplantation was offered. Twenty-four families (68%) chose
      palliation and 11 families (32%) chose cardiac transplantation. Of the 11 infants
      listed for cardiac transplantation, five underwent transplantation. Because of a
      lack of donors after an average wait of 25 days (19 to 31), the remaining six
      infants underwent palliation, with no perioperative deaths. Of the 30 infants
      undergoing palliation, including crossovers, 20 (67%) survived the first
      operative stage. Among the last 19 infants undergoing palliation in 1990, the
      early survival was 84%. Risk factors determined for poor outcome were year of
      operation (p less than 0.001) and circulatory arrest time greater than 50 minutes
      (p less than 0.001). Among the 13 infants undergoing palliation with a
      circulatory arrest time of less than 50 minutes, there were 12 survivors (92%);
      among 12 having a circulatory arrest time of more than 50 minutes, there were
      four survivors (33%). At intermediate follow-up, six infants have undergone
      second-stage procedures (Glenn), with five survivors. There were eight late
      deaths, four caused by respiratory infections and four caused by cardiac
      problems, including a thrombosed shunt in one infant. Three of five infants are
      alive and doing well after cardiac transplantation. Size of aorta, tricuspid
      regurgitation, and ventricular wall thickness did not prove to be risk factors.
      Given the existing data, we believe these infants should be managed selectively
      on the basis of donor availability and family wishes.

PMID- 1377312
TI  - The effect of basic fibroblast growth factor and omentopexy on revascularization
      and epithelial regeneration of heterotopic rat tracheal isografts.
AB  - Donor airway ischemia is a significant problem after clinical lung
      transplantation despite the use of omentopexy for accelerated local bronchial
      revascularization. Several growth factors have been shown to induce angiogenesis
      in vitro and in vivo. In the present study the quantitative effects on tracheal
      revascularization and epithelial regeneration of omentopexy and continuous local
      administration of basic fibroblast growth factor were investigated in a
      heterotopic rat tracheal isograft model. Tracheas were harvested from donor rats
      and heterotopically implanted into the omentum of syngeneic recipient rats.
      Animals were randomly assigned to study groups differing only in treatment of the
      tracheal segments: omental wrap for 2, 7, or 14 days; omental wrap plus
      continuous local administration of basic fibroblast growth factor for 7 or 14
      days; or omental wrap plus local application of saline for 7 or 14 days. Two, 7,
      or 14 days after the animals were put to death, the vascularity of the tracheal
      segments and attached omentum and the tracheal epithelial morphology were
      assessed in a blinded fashion with use of light microscopy and morphometric image
      analysis. Vascularity in tracheal segments treated with basic fibroblast growth
      factor was significantly (p less than 0.05) greater than in control tracheas
      after 7 and 14 days. Epithelial regeneration was also improved in the basic
      fibroblast growth factor-treated groups at days 7 and 14 (p less than 0.05). We
      conclude that continuous local administration of basic fibroblast growth factor
      enhances early revascularization of tracheal segments induced by omentopexy and
      accelerates epithelial regeneration in a heterotopic rat tracheal isograft model.

PMID- 1377314
TI  - Anticoagulation policy during use of aprotinin in cardiopulmonary bypass.

PMID- 1377315
TI  - Guidelines for monitoring heparin by the activated clotting time when aprotinin
      is used during cardiopulmonary bypass.

PMID- 1377316
TI  - Equivalent eighteen-hour lung preservation with low-potassium dextran or Euro
      Collins solution after prostaglandin E1 infusion.
AB  - Improved techniques of pulmonary preservation would help alleviate the critical
      shortage of donor organs in lung transplantation and would improve early graft
      function. A previous study demonstrated that cold pulmonary artery flush with low
      potassium dextran solution was superior to Euro-Collins solution in preservation
      of canine lung allografts stored for 12 hours when no pulmonary vasodilator was
      used before donor lung flush. The present study was designed to determine whether
      donor pretreatment with prostaglandin E1 would affect the superiority of low
      potassium dextran as a preservation solution. Prostaglandin E1 was infused (50
      micrograms/min) in 12 donor dogs until potent vasodilation was demonstrated. Low
      pressure pulmonary artery flush (50 ml/kg) with either Euro-Collins or low
      potassium dextran solution (n = 6 for each group) was performed at 4 degrees C in
      a randomized, blinded fashion. Heart-lung blocks were extracted and stored at 4
      degrees C for 18 hours before left lung allografting. Inflatable cuffs were
      placed around each pulmonary artery, allowing independent study of the native and
      transplanted lungs. All 12 recipient dogs survived the 3-day assessment period.
      Lungs flushed and stored in Euro-Collins or low-potassium dextran solution
      provided equivalent gas exchange function on day 0 (arterial oxygen tension: Euro
      Collins 289 +/- 105 mm Hg versus low-potassium dextran 265 +/- 111 mm Hg; mean +/
      standard error of the mean) and on day 3 (Euro-Collins 516 +/- 45 mm Hg versus
      low-potassium dextran 354 +/- 77 mm Hg; p = 0.10). Mean pulmonary artery
      pressures in the transplanted lung were not significantly different in the Euro
      Collins and low-potassium dextran groups on day 0 (21.4 +/- 2 mm Hg versus 33.7
      +/- 5 mm Hg, respectively; p = 0.09) or on day 3 (20.2 +/- 2.7 mm Hg versus 24.2
      +/- 5.1 mm Hg, respectively; p = 0.50). We conclude that there was no advantage
      of low-potassium dextran over Euro-Collins as a flush solution in this 18-hour
      canine single lung allograft model in which prostaglandin E1 was administered
      before pulmonary artery flush.

PMID- 1377318
TI  - Modulators of nitric oxide synthesis.

PMID- 1377317
TI  - Allergic rhinitis.
AB  - Allergic rhinitis is a common disease with characteristic symptoms affecting the
      eyes, ears, and face as well as the nose. A detailed history is the foundation of
      a correct diagnosis. Laboratory tests may be needed to supplement this in
      atypical presentations. A combination of pharmacotherapy, immunotherapy, and
      environmental control may be required to control and prevent symptoms.

PMID- 1377319
TI  - Dye-enhanced laser welding for skin closure.
AB  - The use of a laser to weld tissue in combination with a topical photosensitizing
      dye permits selective delivery of energy to the target tissue. A combination of
      indocyanine green (IG), absorption peak 780 nm, and the near-infrared (IR)
      alexandrite laser was studied with albino guinea pig skin. IG was shown to bind
      to the outer 25 microns of guinea pig dermis and appeared to be bound to
      collagen. The optical transmittance of full-thickness guinea pig skin in the near
      IR was 40% indicating that the alexandrite laser should provide adequate tissue
      penetration. Laser "welding" of skin in vivo was achieved at various
      concentrations of IG from 0.03 to 3 mg/cc using the alexandrite at 780 nm, 250
      microseconds pulse duration, 8 Hz, and a 4-mm spot size. A spectrum of welds was
      obtained from 1- to 20-W/cm2 average irradiance. Weak welds occurred with no
      thermal damage obtained at lower irradiances: stronger welds with thermal damage
      confined to the weld site occurred at higher irradiances. At still higher
      irradiances, local vaporization occurred with failure to "weld." Thus, there was
      an optimal range of irradiances for "welding," which varied inversely with dye
      concentration. Histology confirmed the thermal damage results that were evident
      clinically. IG dye-enhanced laser welding is possible in skin and with further
      optimization may have practical application.

PMID- 1377320
TI  - Comparative study of laser and scalpel nerve transections.
AB  - This investigation was designed to compare standard scalpel transections of the
      tibial branch of the rat sciatic nerve with those performed using either a
      milliwatt carbon dioxide (CO2) or a potassium titanyl phosphate (KTP/532) laser.
      Four transection groups consisted of nerves sectioned with (1) scalpel (control),
      (2) milliwatt CO2 laser, (3) KTP/532 with microscope attachment, and (4) KTP/532
      laser with 400-microns bare fiber. Each laser was used with the same parameters:
      10 watts, 0.4-mm spot size, and continuous-wave mode. Horseradish peroxidase
      (HRP) was applied to the proximal stump for 30 min, and the animals were
      sacrificed 24 h later. Horseradish peroxidase (HRP)-labeled motoneuron cell
      bodies in the lumbar spinal cord were then counted. The average numbers of
      labeled neurons in each group were as follows: group I (n = 14) 518, group II (n
      = 8) 424, group III (n = 8) 351, and group IV (n = 8) 283. The standard
      deviations were quite large, however. When all laser transections were pooled and
      compared with paired scalpel transections, we found a significant difference,
      both by the paired t-test (P = 0.016) and by the Wilcoxon matched-paired test (P
      = 0.02). We conclude that laser transection significantly diminishes the number
      of neurons labeled by the retrograde transport of HRP.

PMID- 1377321
TI  - Relationship between serotonergic measures in periphery and the brain of mouse.
AB  - Circadian rhythm and the relationship between the concentration of serotonin
      (5HT) and related substances (5-hydroxyindoleacetic acid; 5HIAA and tryptophan;
      Trp) in mouse brain, stomach and blood have been studied. All factors underwent
      circadian changes in the brain and blood. 5HT and 5HIAA levels in the stomach
      showed no circadian fluctuation. The concentrations of 5HT in the brain and blood
      did not correlate. Significant correlations were found between other serotonergic
      parameters analyzed in brain, stomach and blood. A significant negative
      correlation was observed between brain 5HIAA and blood 5HIAA. The concentration
      of tryptophan in the brain was correlated with the plasma total tryptophan level.
      There was fairly significant correlation (p less than 0.06) between brain
      serotonin and plasma tryptophan levels. The brain serotonin and tryptophan levels
      were strongly correlated (R = 0.410, p less than 0.03). Significant negative
      correlation was found between serotonin in the blood and serotonin in the stomach
      as well as between its level in the brain and in the stomach. The significance of
      these findings and their relationship to the use of peripheral serotonergic
      system as a model of neurons are discussed.

PMID- 1377323
TI  - Axonal injury in closed head injury by assault: a quantitative study.
AB  - Due to the controversy in the literature regarding the time course of axonal
      balloon formation in human material, we wished to determine if it was possible to
      diagnose axonal injury before the development of axonal balloonings. The
      hypothesis was that the presence of axonal swellings or axonal enlargements
      associated with a glial reaction could be used as a diagnostic aid in human
      axonal injury before 12 hours. The brains of eight individuals that survived for
      less than 48 hours following head injury, and also had evidence of axonal injury
      using the criteria of Vanezis et al. (1987), were systematically studied by
      looking at axonal swellings, axonal balloonings, reactive astrocytes, maximum
      diameter of axonal enlargements and density of axonal enlargements. Controls were
      eight selected cases without neurological disease. The variables studied were
      assessed in 25 fields from ten different areas of the brain, using silver stains
      and immunoperoxidase for glial fibrillary acidic protein (GFAP). Logarithms of
      one plus the count of each variable were taken from the raw data and these were
      analysed using percentile distribution and the median, the t-test, Mann-Whitney U
      test and the Wilcoxon signed rank test. We conclude that quantitation of axonal
      damage allows the detection of mild degrees of axonal injury that could be
      overlooked on routine examination, and that the criteria of axonal enlargements,
      rather than axonal balloonings, are indications of axonal damage, cannot be
      endorsed with the evidence provided.

PMID- 1377322
TI  - Differential effects of galanin and neuropeptide Y on extracellular
      norepinephrine levels in the paraventricular hypothalamic nucleus of the rat: a
      microdialysis study.
AB  - Evidence suggests that the peptides galanin (GAL) and neuropeptide Y (NPY)
      interact with the amine norepinephrine (NE) in the hypothalamic paraventricular
      nucleus (PVN) to stimulate feeding behavior. To directly investigate the nature
      of these interactions, extracellular levels of PVN NE were monitored in freely
      moving rats using the microdialysis/HPLC technique. Following PVN administration
      of GAL (0.3 nmol), NPY (78 pmol) or Ringer's solution, local NE levels were
      measured at 20-min intervals for 2 hrs postinjection, under two feeding
      conditions, namely, in the presence or absence of food. The results demonstrate
      different effects of these peptides on endogenous NE levels. Following GAL
      administration, PVN NE levels were enhanced by 80 to 90%, up to 40 min
      postinjection, independent of food availability. In contrast, following NPY
      injection, NE levels were significantly reduced 20 min postinjection with food
      absent, and when food was available, NE levels tended to be enhanced. These
      results, consistent with pharmacological and biochemical studies, reveal
      different patterns of peptide-amine interactions in the PVN.

PMID- 1377324
TI  - [Pancreatic exocrine and endocrine functions stimulated with secretin and
      thyrotropin-releasing hormone in patients with hyperparathyroidism].
AB  - This study was designed to investigate pancreatic exocrine and endocrine
      secretion stimulated with secretin and thyrotropin-releasing hormone (TRH) in
      hyperparathyroidism. Pancreatic exocrine secretion during 30 min stimulated by
      constant secretin infusion of 1U/kg/hour was significantly increased in patients
      with secondary hyperparathyroidism compared with controls and patients with
      primary hyperparathyroidism. Intravenous administration of TRH at a dose of 20
      micrograms/kg/hour, superimposed on secretin, produced a significant decrease of
      pancreatic exocrine secretion in both primary and secondary hyperparathyroidism
      but not in control. Serum insulin, glucagon and secretin levels were
      significantly higher in the subjects of both primary and secondary
      hyperparathyroidism than those of controls. Serum glucagon and secretin levels
      were significantly higher in secondary hyperparathyroidism than primary
      hyperparathyroidism. The pancreatic endocrine secretion was not influenced by TRH
      administration. Pancreatic exocrine secretion was not changed by
      parathyroidectomy in patients with primary hyperparathyroidism. As for endocrine
      secretion, however, only serum secretin level decreased to the level before
      parathyroidectomy. In this study, it was speculated that the increase of
      pancreatic secretion in secondary hyperparathyroidism may be due to
      hypersecretinemia, and the decrease of exocrine secretion by TRH in primary and
      secondary hyperparathyroidism may be resulted from the direct effect of TRH on
      the pancreatic acinar cells.

PMID- 1377325
TI  - Regulation by phorbol ester and protein kinase C inhibitors, and by a protein
      phosphatase inhibitor (okadaic acid), of P-glycoprotein phosphorylation and
      relationship to drug accumulation in multidrug-resistant human KB cells.
AB  - Covalent modification by phosphorylation is a characteristic of the P
      glycoproteins expressed in multidrug-resistant cells. This report describes
      analysis of P-glycoprotein phosphorylation in multidrug-resistant human KB-V1
      cells and a study of the relationship of phosphorylation and drug accumulation.
      In isolated membranes, phosphorylation of P-glycoprotein by purified protein
      kinase C (PKC) was rapid, and time-dependent dephosphorylation was inhibited by
      okadaic acid, an inhibitor of type 1 and type 2A protein phosphatases. In 32P
      labeled intact KB-V1 cells, P-glycoprotein phosphorylation was stimulated by both
      12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of PKC, and okadaic
      acid. Two-dimensional thin layer tryptic phosphopeptide maps indicated that the
      sites of phosphorylation were similar in control, TPA-treated, and okadaic acid
      treated cells and that they corresponded to those phosphorylated by PKC in vitro.
      The protein kinase inhibitor staurosporine, and the PKC-selective inhibitors
      calphostin C and the alkyl-lysophospholipid 1-O-octadecyl-2-O-methyl-rac-glycero
      3-phosphocholine, inhibited P-glycoprotein phosphorylation in vitro and in intact
      cells. Drug accumulation assays demonstrated that in KB-V1 cells TPA caused a
      decrease, whereas staurosporine and calphostin C caused an increase, in
      accumulation of [3H]vinblastine. These compounds did not significantly alter
      [3H]vinblastine levels in drug-sensitive KB-3 cells. These results suggest that
      PKC is chiefly responsible for P-glycoprotein phosphorylation in KB-V1 cells,
      that membrane-associated protein phosphatases 1 and 2A are active in
      dephosphorylation of P-glycoprotein, and that phosphorylation of P-glycoprotein
      may be an important mechanism for modulation of drug-pumping activity.

PMID- 1377326
TI  - Determination of the amino acid residues in substance P conferring selectivity
      and specificity for the rat neurokinin receptors.
AB  - We have measured the affinity of various analogs and fragments of the tachykinin
      substance P for the cloned rat NK1, NK2, and NK3 receptors heterologously
      expressed in Chinese hamster ovary cells. The hydrophobic carboxyl-terminal
      pentapeptide sequence substance P-(7-11) binds with similar affinity (2-20
      microM) to all three receptors. Our data suggest that addition of one to three
      amino-terminal residues to this sequence results in the optimization of its
      interaction within the binding pocket of the NK1 receptor. The addition of Pro
      Gln-Gln to the carboxyl-terminal pentapeptide sequence increases affinity for the
      NK1 receptor, either by providing additional binding interactions or by modifying
      the conformation of the carboxyl-terminal sequence. This latter hypothesis is
      supported by the observation that physalaemin and phyllomedusin, which also
      contain a proline residue in the position analogous to the proline residue 4 of
      substance P, are also selective for NK1 receptors. Tachykinins that lack this
      proline have no higher affinity for NK1 than [pGlu] substance P-(6-11).
      Conversely, addition of Pro-Gln-Gln to the carboxyl-terminal pentapeptide
      sequence is unfavorable for NK2 and NK3 receptor binding. Preliminary data
      suggest that tachykinins with high affinity (Kd less than 500 nM) for NK2
      receptors contain an aspartate residue in the position analogous to residue 5 of
      substance P, suggesting that an ionic interaction with the receptor may
      contribute binding energy. Further experiments will be required to determine the
      structural determinants of the NK1, NK2, and NK3 receptors responsible for these
      binding properties.

PMID- 1377328
TI  - Induction of NADPH-dependent diaphorase and nitric oxide synthase activity in
      aortic smooth muscle and cultured macrophages.
AB  - Lipopolysaccharide (LPS), either alone or in combination with cytokines, induces
      nitric oxide (NO) synthase activity in cells that normally release little or no
      NO. In arterial smooth muscle cells and various macrophage cell lines, NO
      synthase activity is induced after several hours of incubation with LPS. In
      brain, NADPH-dependent diaphorase activity has been associated with constitutive
      NO synthase. Here we show that incubation of rat aorta or cultured macrophages
      with LPS causes a time-dependent induction of NO synthase. The NO synthase
      activity in both rat aorta and macrophages was calcium independent and inhibited
      by NG-monomethyl-L-arginine and NG-nitro-L-arginine. We also found that LPS
      caused a time-dependent induction in NADPH-dependent diaphorase activity in both
      rat aorta and cultured macrophages. The diaphorase activity was mainly NADPH
      dependent and NADH independent. NO synthase activity and NADPH-diaphorase
      activity in crude cytosol from LPS-treated macrophages were found to co-purify,
      using 2',5'-ADP-Sepharose followed by Superose-6 gel permeation chromatography.

PMID- 1377327
TI  - Effects of hexachlorocyclohexanes on gamma-aminobutyric acid receptors expressed
      in Xenopus oocytes by RNA from mammalian brain and retina.
AB  - Poly(A)+ RNA from rat cerebral cortex expresses gamma-aminobutyric acid (GABA)
      activated membrane current responses in Xenopus oocytes, mediated by GABAA
      receptors (IG-Actx). In contrast, RNA from bovine retina expresses GABA responses
      composed of two pharmacologically distinct Cl- currents, one mediated by GABAA
      receptors (IG-Aret) and the other by atypical GABA receptors that are resistant
      to bicuculline and are not activated by baclofen (IG-BR). The pharmacology of the
      bicuculline/baclofen-insensitive GABA receptors was further investigated by
      comparing actions of hexachlorocyclohexane (HCH) enantiomers on GABA-activated
      membrane currents expressed in oocytes by brain and retina RNA. gamma-HCH
      (lindane) was a potent inhibitor of IG-Actx, with suppression of currents
      detectable at concentrations as low as 50 nM. The IC50 for gamma-HCH, calculated
      from inhibitory effects on maximum IG-Actx (current elicited by 3 mM GABA), was
      7.3 +/- 3 microM. Inhibitory effects of gamma-HCH on IG-Aret were qualitatively
      similar to those described for IG-Actx. In contrast, alpha-HCH and delta-HCH
      induced clear positive modulation of IG-Actx elicited by low (e.g., 10 microM)
      concentrations of GABA. Thresholds for the modulatory effects of alpha-HCH and
      delta-HCH were between 100 and 300 nM, with maximum levels of potentiation (5-7
      fold) between 20-50 microM. Potentiation of IG-Actx by alpha- and delta-HCH was
      reversible and largely insensitive to the benzodiazepine antagonist flumazenil (1
      microM). Assays on maximum IG-Actx indicated that alpha-HCH (10-100 microM)
      caused only marginal reductions in response (less than or equal to 15%), whereas
      delta-HCH had stronger inhibitory effects (IC50, 20-30 microM). At concentrations
      between 0.1 and 50 microM, beta-HCH induced only 10-25% facilitation of IG-Actx
      elicited by 10 microM GABA and had no clear effects on maximum responses. IG-BR
      was also potently inhibited by gamma-HCH. Thresholds for detecting reductions in
      current were approximately 20 nM, and the IC50 calculated from effects on maximum
      responses was 5.8 +/- 2 microM. However, neither alpha-HCH nor delta-HCH (1-100
      microM) induced any potentiation of IG-BR. alpha-HCH had some weak inhibitory
      effects that were largely surmountable, whereas delta-HCH and beta-HCH were
      essentially inactive. These experiments raise the possibility that alpha- and
      delta-HCH constitute a novel class of GABAA receptor modulators, which might
      prove to be useful for investigating the mechanisms underlying regulation of
      GABAA receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1377329
TI  - Gene expression during newt limb regeneration.

PMID- 1377330
TI  - Mutation induction and DNA adduct formation in Chinese hamster ovary cells
      treated with 6-nitrochrysene, 6-aminochrysene and their metabolites.
AB  - 6-Nitrochrysene, 6-aminochrysene and several of their metabolites were assayed
      for mutagenic activity at the hypoxanthine-guanine phosphoribosyl transferase
      (hprt) locus in DNA-repair-proficient Chinese hamster ovary (CHO-K1) cells and
      excision-repair-deficient CHO-UV5 cells. Mutagen-DNA adducts were analyzed by 32P
      postlabeling in cells treated under the conditions of the mutagenicity assay and
      compared with the adduct patterns produced from the in vitro reaction of
      metabolites of 6-nitrochrysene and 6-aminochrysene with calf-thymus DNA. The
      mutagenic activities of the test compounds in the presence of a liver homogenate
      (S9) fraction from Aroclor 1254-pretreated rats, expressed as the number of
      mutants per 10(6) cells per nmole test compound per ml, in CHO-K1 and CHO-UV5
      cells, respectively, were as follows: 6-nitrochrysene, 0.3 and 4; 6
      aminochrysene, 35 and 117; 6-nitrochrysene-1,2-dihydrodiol, 1 and 6; 6
      aminochrysene-1,2-dihydrodiol, 488 and 644; chrysene (run as a positive control),
      12 and 28. 6-Nitrosochrysene was a direct-acting mutagen, yielding 127 and 618
      mutants per 10(6) cells per nmole per ml in CHO-K1 and CHO-UV5 cells,
      respectively. Mutagen-DNA adduct analysis indicated that cells treated with 6
      aminochrysene in the presence of S9 or 6-nitrosochrysene in the absence of S9
      contained an adduct pattern identical to that derived from the in vitro reaction
      of N-hydroxy-6-aminochrysene with calf-thymus DNA. Cells treated with 6
      aminochrysene-1,2-dihydrodiol plus S9 contained a single mutagen-DNA adduct that
      was distinct from those derived from N-hydroxy-6-aminochrysene. Based on
      comparison with previous studies, this adduct is presumed to be derived from 1,2
      dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-aminochrysene. Cells treated with 6
      nitrochrysene plus S9 and 6-nitrochrysene-1,2-dihydrodiol plus S9 contained a
      single major chromatographically identical adduct that was apparently derived
      from N-hydroxy-6-aminochrysene-1,2-dihydrodiol. The results indicate that 6
      nitrochrysene, 6-aminochrysene and their metabolites are mutagenic in CHO cells,
      but that the major activation pathway for 6-nitrochrysene and 6-nitrochrysene-1,2
      dihydrodiol in this system differs from previously described pathways.

PMID- 1377332
TI  - Cytogenetic analysis of chromosomal aberrations of peripheral lymphocytes in
      workers occupationally exposed to nickel.
AB  - The authors carried out a cytogenetic examination of chromosomal aberrations of
      peripheral lymphocytes (100 cells evaluated in each sample) with simultaneous
      monitoring of the level of exposure by means of determination of nickel in the
      urine, serum and hair. The series included 21 workers occupationally exposed to
      nickel at two workshops producing NiO (6 persons) and NiSO4 (15 persons) in a
      chemical plant. At the same time a comparable control group, i.e., 19 workers of
      the same chemical plant but without any direct occupational nickel exposure
      (clerks, service men, etc.), were examined in the same way. In the exposed group
      chromosomal aberrations of peripheral lymphocytes were detected with an average
      value of 6.41 +/- 1.9% (range 2-14%); in the group producing NiO it was, on the
      average, 9.5 +/- 3.2% (range 7-14%) whereas in the NiSO4 production workers it
      was only 5.2 +/- 1.9% (range 2-10%). There was a dependence of chromosomal
      aberrations of peripheral lymphocytes on the exposure time and on the nickel
      content of the biological material. Significantly increased values (in contrast
      to the normal value of chromosomal aberrations of peripheral lymphocytes, up to
      2%) were detected in the control group as well (average value of 4.05 +/- 2.27%,
      range 1-10%). The authors explain this fact by the nickel-polluted environment of
      the whole observed chemical plant.

PMID- 1377331
TI  - Cytogenetic effects of pesticides. IV. Cytogenetic effects of the insecticides
      Gardona and Dursban.
AB  - The cytogenetic effects of the insecticides Gardona and Dursban were
      investigated. The toxicity and ability of both insecticides to induce chromosome
      aberrations and sister-chromatid exchange in vitro was tested in a primary
      culture of mouse spleen cells, in order to assess the potential mutagenicity of
      both insecticides. The concentrations 10(-7)-10(-3) M were used for testing the
      toxic effects of the insecticides. Both Gardona and Dursban were toxic to spleen
      cell cultures and the percentage of viable cells decreased as the concentration
      of the insecticide was increased. It reached 76.8% and 77.8% of control after
      treatment with the highest concentration tested (10(-3) M) of Gardona and Dursban
      respectively. Gardona at 0.25, 0.50, 1.0 and 2.0 micrograms/ml, and Dursban at
      0.50, 1.0, 2.0 and 4.0 micrograms/ml were tested for the induction of chromosome
      aberrations and sister-chromatid exchanges. All of the tested concentrations of
      both insecticides induced a high percentage of metaphases with chromosomal
      aberrations in cultured mouse spleen cells after 4-h treatment. The frequency of
      SCEs/cell increased with increasing concentration of the insecticides. It reached
      11.92 +/- 0.14/cell and 13.40 +/- 0.20/cell after treatment with Gardona (2
      micrograms/ml) and Dursban (4 micrograms/ml), respectively, compared with 8.2 +/-
      0.19/cell and 7.6 +/- 0.15/cell in the solvent control. The presented results
      indicate that both Gardona and Dursban in the tested concentrations are mutagenic
      in mouse spleen cell cultures.

PMID- 1377333
TI  - Normal chromosomal aberration frequencies in peripheral lymphocytes of healthy
      human volunteers exposed to a maximum daily dose of paracetamol in a double blind
      trial.
AB  - Paracetamol (acetaminophen) has been examined for mutagenic potential in numerous
      studies: gene mutation tests consistently gave negative results while in vitro
      chromosomal aberration tests showed equally consistently positive effects. In
      vivo studies for chromosome breaking activity gave clearly negative, equivocal or
      weakly positive results. In particular two reports have indicated that human
      volunteers taking a maximum daily dose of paracetamol (3 x 1000 mg over 8 h)
      exhibited significantly elevated frequencies of chromatid breaks in their
      peripheral lymphocytes 24 h later. In the one study evaluating the time course,
      levels returned to normal between 3 and 7 days later. We performed a carefully
      controlled double-blind study in which volunteers were pre-screened for normal
      liver function, they all were non-smoking and their diet and environmental
      exposures were controlled during the study. Cell-cycle kinetics were monitored
      and paralleled and a placebo group was included. Although a larger number of
      cells than in the other studies was analysed we were unable to reproduce their
      findings. No significant increases in structural chromosome aberrations (CA) were
      found either when the paracetamol group (male, female or both) post-dosing values
      were compared with pre-dosing values, or when treated groups at any sampling time
      were compared with the placebo groups. There was not even any evidence that
      individuals responded to the clastogenic potential of paracetamol or that a group
      response may have been masked by non-responders. In conjunction with the recently
      published results of the NTP bioassay, showing no carcinogenic activity in mice
      and no carcinogenic activity in rats except an increase of mononuclear cell
      leukaemia in female rats which is of doubtful relevance, the study presented here
      argues that paracetamol does not pose an unacceptable (if any)
      genotoxic/carcinogenic risk to man.

PMID- 1377334
TI  - Cytogenetic studies of workers from the rubber industry.
AB  - Lymphocytes from 21 vulcanizers from a tire factory were analyzed for the
      presence of chromosome aberrations (CAs), sister-chromatid exchanges (SCEs) and
      for proliferation indices (PIs). An increase in the frequencies of CAs and SCEs
      and a decrease in PIs were observed. Cytogenetic parameters were correlated with
      age, smoking habits, and duration of occupational exposure. From the present
      study it can be concluded that cigarette smoking enhances the genotoxic effects
      of mixtures of chemicals to which workers in the rubber industry are exposed.

PMID- 1377335
TI  - Baseline and phosphoramide mustard-induced sister-chromatid exchanges in
      pharmacists handling anti-cancer drugs.
AB  - Determinations of baseline and mutagen-induced sister-chromatid exchanges (SCE)
      have been used as indicators of previous mutagen exposure in several human
      populations. Mutagen-induced SCE is based on the premise that a genetic outcome
      may depend not only on a present exposure, but also on a cell's "memory" of
      previous exposure. The genotoxicity of some anti-cancer drugs including
      cyclophosphamide (CP) has been studied by determining baseline and mutagen
      induced SCE in peripheral blood lymphocytes in treated cancer patients. This
      study examined the in vivo genotoxic effects of occupational exposure to anti
      cancer drug handling by relating baseline and phosphoramide mustard (PM) -induced
      SCE levels with duration of anti-cancer drug handling as a surrogate for anti
      cancer drug exposure dose. The mean baseline SCE for the population was 5.19 +/-
      0.17 and was not correlated with duration of drug handling. However, a strong
      correlation was demonstrated between inducible SCE values and life-time duration
      of drug handling with r = 0.63 (p less than 0.0001 for low-dose PM challenge (0.1
      mg/ml PM) and r = 0.67 (p less than 0.0001) for high-dose PM challenge (0.25
      mg/ml PM). A similar relationship was seen for PM-induced SCE and duration of
      anti-cancer drug handling for the workers' present job with correlations obtained
      being r = 0.63 (p less than 0.0001) for low-dose PM and r = 0.59 (p less than
      0.0001) for high dose PM. The short-lived nature of the baseline SCE lesion is
      discussed as a limitation in population surveillance studies, as it reflects
      primarily recent mutagen exposure and persists only for days to weeks after
      exposure. The induced SCE measure is postulated to provide an integrating
      dosimeter of remote previous exposure, improving upon the current limitation of
      the baseline SCE measure and allowing the "unmasking" of previous exposure in a
      provocative framework.

PMID- 1377336
TI  - Induction of micronuclei in V79 Chinese hamster cells by tetrachlorohydroquinone,
      a metabolite of pentachlorophenol.
AB  - Tetrachlorohydroquinone, a metabolite of the fungicide pentachlorophenol, induced
      significant dose-related increases in micronuclei in V79 Chinese hamster cells
      without exogenous metabolic activation. The lowest observed effective dose was 10
      microM, where the relative survival was about 62%. At the highest dose tested, 20
      microM, the relative survival was about 8% and the frequency of cells with
      micronuclei was about 6 times the solvent control frequency. The induction of
      micronuclei by tetrachlorohydroquinone was significantly inhibited by the
      hydroxyl radical scavenger dimethyl sulfoxide at 5% (v/v).

PMID- 1377337
TI  - Chinese medicinal herbs modulate mutagenesis, DNA binding and metabolism of
      aflatoxin B1.
AB  - Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in
      traditional Chinese medicine for treating liver, lung and rectal tumors while
      Astragalus membranaceus (AM) and Ligustrum lucidum (LL) are often used as an
      adjunct in cancer therapy. In this study, we determined the effects of aqueous
      extracts of these four herbs on aflatoxin B1 (AFB1)-induced mutagenesis using
      Salmonella typhimurium TA100 as the bacterial tester strain and rat liver 9000 x
      g supernatant as the activation system. The effects of these herbs on [3H]AFB1
      binding to calf-thymus DNA were assessed. Organosoluble and water-soluble
      metabolites of AFB1 were extracted and analyzed by high-performance liquid
      chromatography (HPLC). Mutagenesis assays revealed that all of these herbs
      produced a concentration-dependent inhibition of histidine-independent revertant
      (His+) colonies induced by AFB1. At a concentration of 1.5 mg/plate, SB and OD in
      combination exhibited an additive effect. The trend of inhibition of these four
      herbs on AFB1-induced mutagenesis was: SB greater than LL greater than AM. LL, OD
      and SB significantly inhibited AFB1 binding to DNA, reduced AFB1-DNA adduct
      formation, and also significantly decreased the formation of organosoluble
      metabolites of AFB1. Our data suggest that these Chinese medicinal herbs possess
      cancer chemopreventive properties.

PMID- 1377338
TI  - Induction of micronuclei in BALB/c-3T3 cells by selected chemicals and complex
      mixtures.
AB  - The genotoxicity of benzo[a]pyrene, cyclophosphamide, 2-aminoanthracene, 2
      nitrofluorene, nitrosated coal-dust extracts, and cigarette-smoke condensate were
      tested with the micronucleus assay using an established mammalian cell line. The
      results showed that all chemicals and complex mixtures studied induced
      micronuclei in BALB/c-3T3 cells. These results indicate that BALB/c-3T3 cells are
      capable of activating certain promutagens and procarcinogens. It seems,
      therefore, that in addition to cell transformation, the micronucleus assay in
      BALB/c-3T3 cells without an exogenous activation system may be useful for in
      vitro studies to detect genotoxic chemicals and complex mixtures.

PMID- 1377339
TI  - Comments on the paper 'The non-genotoxicity to rodents of the potent bladder
      carcinogens o-anisidine and p-cresidine'.

PMID- 1377340
TI  - Micronucleated cells in nasal mucosa of formaldehyde-exposed workers.
AB  - The frequency of micronuclei (MN) and cytology of respiratory nasal mucosa cells
      were evaluated in 15 non-smokers exposed to formaldehyde in a plywood factory.
      Each subject was paired with a control matched for age and sex. Mean levels of
      exposure to formaldehyde ranged from about 0.1 mg/m3 in the sawmill and shearing
      press departments to 0.39 mg/m3 in the warehouse area. There was a contemporary
      exposure to low levels of wood dust (inspirable mass ranged from 0.23 mg/m3 in
      the warehouse to 0.73 mg/m3 during sawing operations). Nasal respiratory cell
      samples were collected by an otorhinolaryngologist near the inner turbinate using
      a brush for endocervical cytology. After staining (Feulgen plus Fast Green and
      Papanicolaou's method for MN analysis and cytology, respectively), about 6000
      cells were screened for micronuclei and scored in parallel for cytology according
      to a histopathological scale. A higher frequency of micronucleated cells was
      observed in the exposed group than in the controls (0.90 +/- 0.47 vs. 0.25 +/-
      0.22, Mann-Whitney U test: p less than 0.01). Cytological examination indicated
      chronic phlogosis in the nasal respiratory mucosa of plywood factory workers,
      with a high frequency of squamous metaplasia cells (mean score 2.3 +/- 0.5 vs.
      1.6 +/- 0.5 in the control group, Mann-Whitney U test: p less than 0.01).

PMID- 1377341
TI  - Evaluation of genotoxicity of tert.-butylhydroquinone in an hepatocyte-mediated
      assay with V79 Chinese hamster lung cells and in strain D7 of Saccharomyces
      cerevisiae.
AB  - tert.-Butylhydroquinone (TBHQ) has been reported to be genotoxic in some short
      term assays but non-genotoxic in others. We have examined cytotoxicity and
      genotoxicity of TBHQ, a principal metabolite of the phenolic antioxidant 2(3)
      tert.-butyl-4-hydroxyanisole (BHA), in an hepatocyte-mediated assay with V79
      Chinese hamster lung cells including both sister-chromatid exchange (SCE) and
      thioguanine-resistance (TGR) endpoints. The ability of BHA and of TBHQ to elicit
      a genotoxic response in Saccharomyces cerevisiae strain D7 was also investigated.
      In V79 cytotoxicity tests, TBHQ without hepatocytes produced a 50% reduction in
      colony formation at 4.2 micrograms/ml and was lethal to 100% of the cells at
      concentrations above 5 micrograms/ml. At partially cytotoxic dose levels, (0.17
      3.4 micrograms/ml of medium), TBHQ sometimes increased significantly the
      frequency of SCE. TBHQ also produced sporadic statistically significant increases
      in the mutation frequency at the HGPRTase (TGR) gene locus when tested alone or
      with activation by rat or hamster hepatocytes. Mitotic gene conversion and
      reverse mutation were not induced in strain D7 of Saccharomyces cerevisiae by
      exposure to BHA or to TBHQ for 4 h at concentrations as high as 200 micrograms/ml
      for BHA or 500 micrograms/ml for TBHQ, either alone or with activation by rat
      liver S9. Incubation of the yeast cells with BHA or TBHQ for 24 h in growth
      medium without activation also did not induce genotoxic activity. The slight and
      sporadic response to TBHQ in the V79 test system may indicate weak genotoxicity
      which is sensitive to slight differences in test conditions. The classification
      and test strategies adopted for compounds such as TBHQ could have important
      implications for regulatory decisions and for the validation of short-term tests.

PMID- 1377342
TI  - Evaluation of the genotoxic effects of a folk medicine, Petiveria alliacea
      (Anamu).
AB  - Crude extract from a plant known as Petiveria alliacea (Anamu) is used
      extensively as folk medicine in developing countries like Colombia, South
      America. Although the plant is known to contain toxic ingredients potential
      adverse health effects from its use have not been adequately evaluated. We
      investigated its genotoxic activities by conducting a sister chromatid exchange
      (SCE) assay using cells in vitro and in vivo. Lymphocytes from humans were
      treated at 24 h after initiation of culture for 6 h with alcohol extract from the
      folk medicine. Concentrations of 0, 10, 100, 250, 275, 500, 750, and 1000
      micrograms/ml of the extract were used. Significant dose-dependent increase of
      SCE (3.7-7.4 SCE per cell) were observed (analysis of variances, p less than
      0.01). Delay in cell proliferation but not inhibition of mitosis was also
      observed. In another experiment, mice were exposed once orally to 1x, 200x, 300x
      and 400x the human daily consumption dose of Anamu. The induction of sister
      chromatid exchanges in bone marrow cells were investigated. We observed a
      significant dose dependent increase of SCE compared with the saline control (2.15
      4.53; p less than 0.01) and compared with the solvent control (3.04-4.53; p less
      than 0.01). Our data suggest, therefore, that the folk medicine contains
      mutagenic and potentially carcinogenic agents although the medicine is not a
      potent mutagen. Individuals who consume large amounts of this drug may be at risk
      for development of health problems. Further studies with cells from exposed
      individuals and from experimental animals should be conducted to provide a better
      evaluation of health risk from the use of this drug.

PMID- 1377343
TI  - Cytogenetic studies of mice exposed to styrene by inhalation.
AB  - The data for the in vivo genotoxicity of styrene (STY) are equivocal. To evaluate
      the clastogenicity and sister-chromatid exchange (SCE)-inducing potential of STY
      in vivo under carefully controlled conditions, B6C3F1 female mice were exposed by
      inhalation for 6 h/day for 14 consecutive days to either 0, 125, 250 or 500 ppm
      STY. One day after the final exposure, peripheral blood, spleen, and lungs were
      removed and cells were cultured for the analysis of micronucleus (MN) induction
      using the cytochalasin B-block method, chromosome breakage, and SCE induction.
      Peripheral blood smears were also made for scoring MN in erythrocytes. There was
      a significant concentration-related elevation of SCE frequency in lymphocytes
      from the spleen and the peripheral blood as well as in cells from the lung.
      However, no statistically significant concentration-related increases were found
      in the frequency of chromosome aberrations in the cultured splenocytes or lung
      cells, and no significant increases in MN frequencies were observed in
      binucleated splenocytes or normochromatic erythrocytes in peripheral blood
      smears.

PMID- 1377344
TI  - Genotoxicity of 'gudakhu', a tobacco preparation. I. In mice in vivo.
AB  - 'Gudakhu' is a paste-like tobacco preparation used widely in Orissa and
      neighbouring states of India. During use it is rubbed over the teeth and gum with
      a finger tip. Besides tobacco, it contains molasses, lime, red soil and water.
      The genotoxic potential of acetone extract of gudakhu was evaluated in mice in
      vivo using the chromosome aberration assay, micronucleus test and SCE analysis
      following single as well as long-term repeated treatment. The animals received an
      aqueous suspension of the extract via the oral route. Gudakhu extract induced
      significantly high frequencies, compared to controls, of chromosome aberrations,
      micronuclei (MN) and SCEs. Single treatment with different doses clearly revealed
      a distinct dose-dependent increase of the effects in all the assays. Analysis of
      MN in regenerated hepatocytes also indicated a significant positive correlation
      between time-course of chronic treatment and frequencies of micronucleated cells.
      But incidences of chromosome aberrations, MN and SCEs in bone marrow cells
      following repeated treatment for different periods did not differ greatly from
      each other; and these repeated treatment data, particularly in the MNT in bone
      marrow cells and the SCE assay, also did not differ markedly from the respective
      single treatment data for the same dose. This was probably due to the
      proliferative nature of the bone marrow cells.

PMID- 1377345
TI  - Mutagenicity of quinolines in Salmonella typhimurium TA100. A QSAR study based on
      hydrophobicity and molecular orbital determinants.
AB  - The mutagenicity of 33 quinolines in the Salmonella test using TA98 and TA100
      cells has been reported. Significant activity was found only with TA100 cells.
      Quantitative structure-activity relationships (QSAR) could be formulated using
      molecular orbital parameters or Hammett constants and hydrophobic parameters for
      those compounds with substituents in the 6, 7 and 8 positions. The QSAR points to
      the 2-position on the quinoline ring as being the site for activation by S9
      oxidation.

PMID- 1377346
TI  - On the induction of umu gene expression in Salmonella typhimurium strain
      TA1535/pSK1002 by some nitrofurans.
AB  - Several nitrofurans were found to induce umu gene expression in Salmonella
      typhimurium TA1535/pSK1002 as defined on the basis of at least a 2-fold increase
      of beta-galactosidase activity over the background level. beta-Galactosidase
      activity increased with increasing concentrations of the chemical, attained a
      maximum at a concentration which was different for different nitrofurans used,
      and then gradually decreased with a further increase of the nitrofuran
      concentration. The umu gene expression test revealed that the genotoxic activity
      was highest for furazolidone and lowest for 5-nitro-2-furaldehyde.

PMID- 1377347
TI  - Mutagenic activity of dichloroethylamino derivatives of nitronaphthofuran and
      some nitrobenzofurans in the Salmonella/microsome assay.
AB  - The mutagenic activity of five dichloroethylamino 2-nitrobenzofuran derivatives
      and one dichloroethylamino 2-nitronaphthofuran derivative was analysed in the
      Salmonella/microsome assay. We investigated the influence of the position of the
      dichloroethylamino and/or the methoxy groups on the mutagenic activity of these
      nitro arenofurans in S. typhimurium strain TA100 and its variant TA100NR,
      deficient in nitroreductase. Without metabolic activation 7-[bis(2
      chloroethyl)amino]-2-nitronaphtho[2,1-b]furan (1), 4-[bis(2-chloroethyl)amino]-7
      methoxy-2-nitrobenzofuran (2), 7-[bis(2-chloroethyl)amino]-4-methoxy-2
      nitrobenzofuran (5) and 6-[bis(2-chloroethyl)amino]-2-nitrobenzofuran (6) are
      mutagenic in TA100, while 4-[bis(2-chloroethyl)amino]-5-methoxy-2-nitrobenzofuran
      (4) is weakly mutagenic and 5-[bis(2-chloroethyl)-amino]-2-nitrobenzofuran (3)
      toxic. In the NR deficient strain compounds 1, 3 and 6 are strong mutagens and 4
      is weakly positive. The two isomers 2 and 5 are negative in that strain. The
      naphthofuran derivative 1 is highly mutagenic in the absence of S9 mix in both
      strains considered, but less than R7000 (7). A decrease in the electronic
      polarity of compound 1 versus compound 7 according to the hypothesis developed by
      Royer et al. is a possible explanation. After exogenous metabolic activation by
      S9 mix all the compounds tested are highly mutagenic in both Salmonella strains.
      The position of the dichloroethylamino group and/or the presence of a methoxyl on
      the alpha-nitroarenofuran derivatives seem to modify the activity of bacterial as
      well as exogenous nitroreductases or other activating enzymes.

PMID- 1377348
TI  - Chromosome aberrations reduced in whole-body irradiated mice by pretreatment with
      cyanide.
AB  - Male mice exposed to single, whole-body 60Co irradiation, were injected
      intraperitoneally with a non-toxic dose of KCN, 2 min or 20 min prior to
      irradiation. Bone-marrow cells were examined for chromatid breaks and chromosome
      aberrations (CA) at different times post-irradiation. The 2 min but not the 20
      min treated mice had a marked reduction in chromatid breaks and chromosome
      aberrations. A study was made of mice exposed to 3.0 Gy (1.8 Gy/min), treated
      with KCN 2 min prior to irradiation and examined 5 min to 30 d post-irradiation.
      After 5 min there were no significant changes in frequency of CA. Subsequently,
      the incidence of CA in the KCN-treated group was reduced compared to the
      irradiated controls. By the 30th day, however, CA frequencies had returned to
      control levels in all groups. No effect of KCN treatment was observed in the
      white or red blood cells. The cytogenetic results were posited to be a function
      of the relative inhibition and recovery times of cyanide affected cytochrome
      oxidase, DNA synthesis, and ATP.

PMID- 1377349
TI  - Insect sex chromosomes, XI. 3H-TdR induces random aberrations in the X
      chromosome(s) of Gryllotalpa fossor (Orthoptera).
AB  - The pattern of titrated thymidine (3H-TdR), a direct precursor of DNA, induced
      aberrations on the X chromosome of Gryllotalpa fossor was examined. 3H-TdR
      produced aberrations randomly distributed over the entire length of the X
      chromosome; breaks were observed in both the eu- and the heterochromatic arms of
      the X chromosome in both the sexes. Since the eu- and the heterochromatic arms
      cannot be distinguished cytologically in this insect, the presence of aberrations
      on both arms of the same X chromosome in the male and damage to both X
      chromosomes in the female indicate that both euchromatic and heterochromatic
      regions (facultative or constitutive) are equally liable to aberrations induced
      by H-TdR. This is in contrast to the non-random induction of aberrations by 3H
      UdR, which causes chromosome damage due to the proximity of the labeled RNA to
      the DNA template during transcription.

PMID- 1377350
TI  - Inhibition of mutagenesis by p-aminobenzoic acid as a nitrite scavenger.
AB  - Nitrite treatment enhances the direct-acting mutagenicity of various foodstuffs
      (e.g., chicken, bloater, the soybean flour 'kinako', and Ban-Ban-Chi sauce) on
      Salmonella typhimurium TA100. p-Aminobenzoic acid (PABA) and glutathione (GSH)
      reduced this mutagenicity; on the other hand, thioproline (TPRO) increased it.
      PABA seemed more effective than TPRO in scavenging nitrite ion. In analysis of
      the reactions of PABA and sodium nitrite under acidic conditions (pH 3.0), p
      hydroxybenzoic acid (PHBA) was identified as a major reaction product. The
      reaction seems to involve two steps, diazotization and diazonium substitution.
      PHBA was not mutagenic to four strains (TA97, TA98, TA100 and TA102) of S.
      typhimurium with or without S9 mix.

PMID- 1377351
TI  - Ethylene dibromide: negative results with the mouse dominant lethal assay and the
      electrophoretic specific-locus test.
AB  - Ethylene dibromide (1,2-dibromoethane; EDB) was tested for the induction of
      dominant lethal and electrophoretically-detectable specific-locus mutations in
      the germ cells of DBA/2J male mice. Males were treated with a single
      intraperitoneal injection of 100 mg/kg EDB and mated to two C57BL/6J females. In
      the dominant lethal assay, matings were carried out to measure the effect of EDB
      on meiotic and postmeiotic stages; germ cells representing spermatogonial stem
      cells were analyzed in the electrophoretic specific-locus test. Neither of these
      germ cell tests produced any evidence that EDB is a germ cell mutagen. It appears
      from these data and those reported in the literature that EDB, a genotoxic
      carcinogen that affects male fertility in some mammalian species, is not
      mutagenic in the germ cells of the male mouse.

PMID- 1377352
TI  - Cytotoxicity of tin on human peripheral lymphocytes in vitro.
AB  - The comparative effects of inorganic and organic tin compounds on chromosomes
      were assessed in human peripheral blood lymphocytes of healthy donors 20-40 years
      of age. The endpoints observed were chromosomal abnormalities, sister-chromatid
      exchanges (SCEs) and cell cycle kinetics. The maximum concentrations which
      reduced the replicative index by about 50%, of stannic chloride and trimethyltin
      chloride were 40 micrograms and 2 micrograms per culture respectively. The tested
      doses were 20 micrograms and 10 micrograms of stannic chloride and 1 microgram
      and 0.5 microgram of trimethyltin chloride. Both doses of stannic chloride
      induced a much higher frequency of chromosomal abnormalities (P less than 0.05-P
      less than 0.001) and a greater reduction of cell cycle kinetics than the
      corresponding relative doses of trimethyltin chloride. The frequencies of
      SCEs/cell induced by the latter were, however, slightly higher than those induced
      by the former.

PMID- 1377353
TI  - Low temperature between conditioning and challenge treatment prevents the
      'adaptive response' of Vicia faba root tip meristem cells.
AB  - When the temperature during intertreatment time (2 h) between conditioning and
      challenge treatment of Vicia faba root tip meristems with either
      triethylenemelamine or maleic hydrazide was reduced from 24 degrees C to 12
      degrees C no adaptive response occurred any more. The yield of metaphases with
      chromatid aberrations under these circumstances was similar to that observed
      after challenge treatment alone, i.e., no reduction occurred. This indicates that
      the metabolic state of the cells is of critical importance for the presence or
      absence of adaptive responses.

PMID- 1377354
TI  - Increased mutagenicity of some nitroimidazoles by non-mutagenic nitrotoluene on
      Klebsiella pneumoniae (fluctuation test).
AB  - In the fluctuation test the mutation frequency of Klebsiella pneumoniae by the 5
      nitroimidazoles panidazole and dimetridazole was increased by adding the non
      mutagenic substances 4-nitrotoluene or toluene-4-sulfonamide. This effect was not
      found with 1-methyl-5-nitroimidazole, metronidazole, ronidazole, nimorazole and 1
      methyl-2-hydroxymethyl-5-nitroimidazole. It is suggested that the molecules of
      panidazole or dimetridazole form some association, which is destroyed by 4
      nitrotoluene or toluene-4-sulfonamide, thus increasing the concentration of
      mutagenic particles.

PMID- 1377355
TI  - Simultaneous analysis of chromosome damage and aneuploidy in cytokinesis-blocked
      V79 Chinese hamster lung cells using an antikinetochore antibody.
AB  - A modified antikinetochore antibody technique was established in the V79 Chinese
      hamster lung cells to simultaneously analyze chromosome damage and aneuploidy
      induced by various agents. The method involved sequential treatment of slides
      with crest serum, fluoresceinated goat-antihuman and swine-antigoat antibodies,
      and propidium iodide. In this method, cytoplasm (green), nuclei or micronuclei
      (red), and kinetochores (yellow), are identified using the same filter setting
      under blue excitation (440-490 nm) with a barrier filter at 520 nm. Using this
      method, three agents, vinblastine (VB), X-rays, and methyl methanesulfonate (MMS)
      were tested for micronucleus/aneuploidy induction. An aneugen, VB and a
      clastogen, X-rays, induced predominantly kinetochore positive (K+) and negative
      (K-) micronucleated binucleate (MNBN) cells, respectively, in a dose-dependent
      fashion. An alkylating agent, MMS, produced both K+ and K- MNBN cells. These
      results are comparable with the results reported in the literature on these
      compounds using various methods and thus demonstrate the usefulness of this assay
      in distinguishing clastogenicity from aneugenicity.

PMID- 1377356
TI  - Solvent extraction efficiencies of mutagenic components from diesel particles.
AB  - In order to determine the efficiency of organic solvent extractions of fresh
      diesel-engine exhaust particles a series of Soxhlet extractions were set up using
      single and sequential extractions of fresh diesel particles with solvents of
      increasing polarities. Single extractions were carried out with methylene
      chloride, methanol, acetone and acetonitrile. A single filter was sequentially
      extracted with methylene chloride followed by methanol, acetone and acetonitrile.
      Methylene chloride extracted the most mutagenicity relative to the other three
      solvents. In addition, methylene chloride extracted 97% of the total extracted
      mutagenicity from a sequential series of extractions. Therefore, we conclude that
      of the solvents tested methylene chloride extracts the highest proportion of
      mutagens from fresh diesel exhaust and little mutagenicity is lost using
      methylene chloride as the only extraction solvent.

PMID- 1377357
TI  - Glycyrrhiza glabra extract as an effector of interception in Escherichia coli
      K12+.
AB  - Glycyrrhiza glabra polar lipid extract contains a number of flavonoids and
      related chemical compounds. Studies on the effectiveness of Glycyrrhiza glabra
      polar lipid extract in intercepting reactive molecules generated from the
      illumination of the photosensitizers rose bengal and phenosafranin indicate that
      it is effective in preventing cytotoxicity against E. coli K12+ in a dose-related
      fashion using illuminated rose bengal. Since only a modest scavenging of singlet
      oxygen generated from phenosafranin is observed, the effects of the extracts are
      less related to singlet oxygen-mediated oxidation of substrate (type II
      reactions) than non-singlet oxygen-mediated oxidation of substrate (type I
      reactions). Elevated levels of glutathione observed in exponentially growing
      cells of E. coli K12 were also observed.

PMID- 1377358
TI  - Genotoxicity of N-acryloyl-N'-phenylpiperazine, a redox activator for acrylic
      resin polymerization.
AB  - N-Acryloyl-N'-phenylpiperazine is a promoter of redox reactions synthesized
      recently, and proposed as an activator for the polymerization of acrylic resins
      for biomedical use. The chemical was analyzed for different genotoxicity
      endpoints, to obtain both information on its possible mutagenic/carcinogenic
      potential and a model analysis of a tertiary arylamine, which belongs to a class
      of chemicals commonly used as polymerization accelerators in the biomaterial
      field. The genotoxicity endpoints considered were: gene mutation in the
      Salmonella test; structural and numerical chromosome alterations in Chinese
      hamster V79 cells, evaluated by the micronucleus test together with an
      immunofluorescent staining specific for kinetochore proteins; in vitro and in
      vivo DNA damage, evaluated in V79 cells and in mouse liver by the alkaline DNA
      elution technique. On the whole, the results indicate that N-acryloyl-N'
      phenylpiperazine is to be regarded not so much as a DNA-damaging agent, but as a
      genomic mutagen. Indeed, it was not mutagenic in Salmonella (though its toxicity
      did not allow testing concentrations over 70 micrograms/plate), and it was weakly
      positive in inducing chromosomal fragmentation in vitro (one positive, not dose
      related, result out of five different doses tested) and in vivo DNA damage
      (increases in DNA elution rate never doubling control values). The chemical was,
      however, clearly positive (with dose-dependent effects up to about 25 times the
      control value) in causing numerical chromosome alterations, at the maximal non
      toxic doses.

PMID- 1377359
TI  - Effect of the antiarrhythmic agent moricizine on survival after myocardial
      infarction.
AB  - BACKGROUND: The Cardiac Arrhythmia Suppression Trial (CAST) tested the hypothesis
      that the suppression of asymptomatic or mildly symptomatic ventricular premature
      depolarizations in survivors of myocardial infarction would decrease the number
      of deaths from ventricular arrhythmias and improve overall survival. The second
      CAST study (CAST-II) tested this hypothesis with a comparison of moricizine and
      placebo. METHODS: CAST-II was divided into two blinded, randomized phases: an
      early, 14-day exposure phase that evaluated the risk of starting treatment with
      moricizine after myocardial infarction (1325 patients), and a long-term phase
      that evaluated the effect of moricizine on survival after myocardial infarction
      in patients whose ventricular premature depolarizations were either adequately
      suppressed by moricizine (1155 patients) or only partially suppressed (219
      patients). RESULTS: CAST-II was stopped early because the first 14-day period of
      treatment with moricizine after a myocardial infarction was associated with
      excess mortality (17 of 665 patients died or had cardiac arrests), as compared
      with no treatment or placebo (3 of 660 patients died or had cardiac arrests); and
      estimates of conditional power indicated that it was highly unlikely (less than 8
      percent chance) that a survival benefit from moricizine could be observed if the
      trial were completed. At the completion of the long-term phase, there were 49
      deaths or cardiac arrests due to arrhythmias in patients assigned to moricizine,
      and 42 in patients assigned to placebo (adjusted P = 0.40). CONCLUSIONS: As with
      the antiarrhythmic agents used in CAST-I (flecainide and encainide), the use of
      moricizine in CAST-II to suppress asymptomatic or mildly symptomatic ventricular
      premature depolarizations to try to reduce mortality after myocardial infarction
      is not only ineffective but also harmful.

PMID- 1377360
TI  - Developmental regulation of NMDA receptor-mediated synaptic currents at a central
      synapse.
AB  - The central nervous system has extraordinary plasticity in early life. This is
      thought to involve N-methyl-D-aspartate (NMDA) receptors which, along with the
      non-NMDA receptors, mediate fast excitatory synaptic transmission. Although NMDA
      receptors may be transiently enhanced early in life, it has not been possible to
      demonstrate directly a functional change in the NMDA receptor-mediated synaptic
      response because of the voltage-dependence of the NMDA conductance and the
      overlapping inhibitory synaptic conductances. Here I report that the duration of
      evoked NMDA-receptor-mediated excitatory postsynaptic currents (e.p.s.cs) in the
      superior colliculus is several times longer at early developmental stages
      compared to that measured in older animals. In contrast, the amplitude of NMDA
      receptor-mediated miniature e.p.s.cs does not change during development. The
      kinetic response of excised membrane patches to a brief activation of NMDA
      receptors is similar to that of the NMDA e.p.s.c, which suggests that the time
      course of the NMDA e.p.s.c. in the superior colliculus reflects slow NMDA channel
      properties as in the hippocampus. Therefore, these data indicate that the
      molecular properties of NMDA receptors are developmentally regulated and thus may
      be controlling the ability of synapses to change in early life.

PMID- 1377361
TI  - FK-506- and CsA-sensitive activation of the interleukin-2 promoter by
      calcineurin.
AB  - Antigen recognition by the T-cell receptor (TCR) initiates events including
      lymphokine gene transcription, particularly interleukin-2, that lead to T-cell
      activation. The immunosuppressive drugs, cyclosporin A (CsA) and FK-506, prevent
      T-cell proliferation by inhibiting a Ca(2+)-dependent event required for
      induction of interleukin-2 transcription. Complexes of FK-506 or CsA and their
      respective intracellular binding proteins inhibit the calmodulin-dependent
      protein phosphatase, calcineurin, in vitro. The pharmacological relevance of this
      observation to immunosuppression or drug toxicity is undetermined. Calcineurin,
      although present in lymphocytes, has not been implicated in TCR-mediated
      activation of lymphokine genes or in transcriptional regulation in general. Here
      we report that transfection of a calcineurin catalytic subunit increases the 50%
      inhibitory concentration (IC50) of the immunosuppressants FK-506 and CsA, and
      that a mutant subunit acts in synergy with phorbol ester alone to activate the
      interleukin-2 promoter in a drug-sensitive manner. These results implicate
      calcineurin as a component of the TCR signal transduction pathway by
      demonstrating its role in the drug-sensitive activation of the interleukin-2
      promoter.

PMID- 1377362
TI  - Identification of calcineurin as a key signalling enzyme in T-lymphocyte
      activation.
AB  - The immunosuppressive drugs cyclosporin A (CsA) and FK506 both interfere with a
      Ca(2+)-sensitive T-cell signal transduction pathway, thereby preventing the
      activation of specific transcription factors (such as NF-AT and NF-IL2A) involved
      in lymphokine gene expression. CsA and FK506 seem to act by interaction with
      their cognate intracellular receptors, cyclophilin and FKBP, respectively (see
      ref. 11 for review). The Ca2+/calmodulin-regulated phosphatase calcineurin is a
      major target of drug-isomerase complexes in vitro. We have therefore tested the
      hypothesis that this interaction is responsible for the in vivo effects of
      CsA/FK506. We report here that overexpression of calcineurin in Jurkat cells
      renders them more resistant to the effects of CsA and FK506 and augments both
      NFAT- and NFIL2A-dependent transcription. These results identify calcineurin as a
      key enzyme in the T-cell signal transduction cascade and provide biological
      evidence to support the notion that the interaction of drug-isomerase complexes
      with calcineurin underlies the molecular basis of CsA/FK506-mediated
      immunosuppression.

PMID- 1377363
TI  - New human gene encoding a positive modulator of HIV Tat-mediated transactivation.
AB  - The human immunodeficiency virus-1 (HIV-1) protein Tat is a potent activator of
      virus gene expression. Tat functions through a sequence known as TAR, located
      immediately downstream of the transcription start site in the long terminal
      repeat. Several observations suggest that cellular factors cooperate with Tat in
      the overall transactivating process. We have isolated a human complementary DNA
      from the new gene MSS1, which may encode such a cellular factor, by
      transcomplementation of a yeast sgv1- mutant. The MSS1 protein shares 42%
      sequence identity with the human TBP-1 protein, which binds Tat in vitro and
      suppresses Tat-mediated transactivation in vivo (ref. 6). We report here that the
      levels of HIV activation by Tat correlate with endogenous levels of MSS1
      messenger RNA. Furthermore, we provide evidence that expression of MSS1 enhances
      the Tat-mediated transactivation. Our results suggest that MSS1 has a key role in
      activation of HIV genes regulated by Tat.

PMID- 1377364
TI  - Emerging cytokine family.

PMID- 1377365
TI  - Molecular diversity of the NMDA receptor channel.
AB  - Two novel subunits of the mouse NMDA receptor channel, the epsilon 2 and epsilon
      3 subunits, have been identified by cloning and expression of complementary DNAs.
      The heteromeric epsilon 1/zeta 1, epsilon 2/zeta 1 and epsilon 3/zeta 1 NMDA
      receptor channels exhibit distinct functional properties in affinities for
      agonists and sensitivities to competitive antagonists and Mg2+ block. In contrast
      to the wide distribution of the epsilon 1 and zeta 1 subunit messenger RNAs in
      the brain, the epsilon 2 subunit mRNA is expressed only in the forebrain and the
      epsilon 3 subunit mRNA is found predominantly in the cerebellum. The epsilon
      1/zeta 1 and epsilon 2/zeta 1 channels expressed in Xenopus oocytes, but not the
      epsilon 3/zeta 1 channel, are activated by treatment with 12-O
      tetradecanoylphorbol 13-acetate. These findings suggest that the molecular
      diversity of the epsilon subunit family underlies the functional heterogeneity of
      the NMDA receptor channel.

PMID- 1377366
TI  - Influenza virus. Amantadine blocks the channel.

PMID- 1377367
TI  - RNA substrate binding site in the catalytic core of the Tetrahymena ribozyme.
AB  - In catalysis by group I introns, the helix (P1) containing the RNA cleavage site
      must be positioned next to the guanosine binding site. We have identified a
      conserved adenine in the catalytic core that contributes to the stability of this
      arrangement and propose that it accepts a hydrogen bond from a specific 2'-OH in
      P1. Such base-backbone tertiary interactions may be generally important to the
      organization of RNA tertiary structure.

PMID- 1377368
TI  - Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen.
AB  - Immunization with myelin basic protein (MBP) induces experimental allergic
      encephalomyelitis (EAE), a prototype of CD4+ T-cell mediated autoimmune disease.
      In rodents, MBP-reactive T-cell clones are specific for a single, dominant
      determinant on MBP and use a highly restricted number of T-cell receptor genes.
      Accordingly, EAE has been prevented by various receptor-specific treatments,
      suggesting similar strategies may be useful for therapy of human autoimmune
      disease. Here we report that in (SJL x B10.PL)F1 mice, immune dominance of a
      single determinant, MBP:Ac1-11, is confined to the inductive phase of EAE. In
      mice with chronic EAE, several additional determinants of MBP in peptides 35-47,
      81-100 and 121-140 recall proliferative responses. Most importantly, reactivity
      to the latter determinants was also detected after induction of EAE with MBP
      peptide Ac1-11 alone; this demonstrates priming by endogenous MBP determinants.
      Thus, determinants of MBP that are cryptic after primary immunization can become
      immunogenic in the course of EAE. Diversification of the autoreactive T-cell
      repertoire due to 'determinant spreading' has major implications for the
      pathogenesis of, and the therapeutic approach to, T-cell driven autoimmune
      disease.

PMID- 1377369
TI  - Protein images obtained by STM, AFM and TEM.
AB  - Scanning tunnelling microscopy and atomic force microscopy, one scanning the
      tunnelling current and the other the repulsive atomic force between same and
      probe, can give high-quality surface topographies of proteins, which have been
      difficult to obtain by more conventional methods such as transmission electron
      microscopy.

PMID- 1377371
TI  - Doctor was thinking of the wrong drug.

PMID- 1377370
TI  - The treatment of intracranial malignant gliomas using orally administered
      tamoxifen therapy: preliminary results in a series of "failed" patients.
AB  - In vitro studies have shown that the nonsteroidal antiestrogen tamoxifen can
      suppress deoxyribonucleic acid synthesis and cell proliferation in cultured human
      gliomas. This growth suppression is independent of its antiestrogenic properties.
      Tamoxifen may act through the inhibition of the enzyme protein kinase C, which
      transduces mitogenic signals from the cell surface to the nucleus. Based on these
      preclinical studies, we initiated a clinical trial of orally administered
      tamoxifen, 20 mg twice daily, to patients with recurrent, progressive malignant
      gliomas who were not candidates for other "failed" protocols, such as
      brachytherapy. No limits were placed on age, Karnofsky Performance Score (KPS),
      or expected survival. Thirty-two patients were entered in the study, 29 with a
      glioblastoma multiforme and 3 with an anaplastic astrocytoma. The mean age of the
      group was 48 years, and the mean KPS was 65. Median survival of the entire cohort
      from the onset of tamoxifen therapy was 17 weeks; the median survival of those
      patients with an initial KPS of 70 or more was 21 weeks. Seven patients survived
      for more than 6 months with no change in their baseline computed tomographic
      scans or KPS on tamoxifen, including 2 patients with computed tomographic
      evidence of regression during the course of therapy. There were no significant
      patient-reported side effects of the treatment. Three patients had thromboembolic
      complications during tamoxifen administration. We conclude that tamoxifen can be
      administered safely to these patients and may show some efficacy against glial
      neoplasms.

PMID- 1377372
TI  - Treatment of human immunodeficiency virus associated with oral aphthous ulcers
      with inhaled steroids.

PMID- 1377373
TI  - Keloids of the external ear.
AB  - Keloid formation is a rare complication of normal scar tissue development, also
      to the surgeon who performs surgery on the external ear. We are presenting 4
      cases of keloid formation which occurred after ear piercing in 2 cases and after
      otoplasty in another 2 cases. The treatment of keloid formation caused
      difficulties and is not unequivocal. Therefore we wish to present our experiences
      as we have seen no cases of keloid formation after otoplasty described in the
      literature.

PMID- 1377374
TI  - Fractionation and antigenic characterization of organelles of Eimeria tenella
      sporozoites.
AB  - Sporozoites of Eimeria tenella were disrupted by sonication and subcellular
      fractions were separated by sucrose gradient ultracentrifugation. Fractions from
      gradients were characterized by electron microscopical appearance and their
      polypeptide and antigenic profiles determined by PAGE and Western blotting with
      antisera to sporozoites and 1st- and 2nd-generation merozoites. Fractions
      containing micronemes, rhoptries or membranes showed markedly different
      polypeptide content and antigenic reactivity. Microneme epitopes were strongly
      conserved between sporozoites and 2nd-generation merozoites whereas the majority
      of rhoptry epitopes and many membrane epitopes were sporozoite specific. The only
      polypeptide of sporozoites which was strongly recognized by antisera raised to
      1st generation merozoites was a microneme antigen of molecular weight
      approximately 100 kDa.

PMID- 1377375
TI  - Effects of three anthelmintics on the tegument of Hymenolepis fraterna (Cestoda).
AB  - The in vivo effects of the anthelmintics taenifugin, VUFB 14170 and VUFB 15269 on
      the tegument of Hymenolepis fraterna have been examined by SEM, TEM and
      cytochemistry. The drugs were given to H. fraterna-infected mice on the 14th day
      post-infection in a single oral dose of 150, 200 and 200 mg/kg, respectively. By
      72 h post-treatment, the drug-induced pathomorphological changes in the tegument
      indicated that all three drugs had a significant effect. Changes were most
      pronounced on the brush border and in the intercellular material. On the apical
      surface, there was blebbing as well as accumulation of membrane fragments over
      the microthrix tips and erosion of the brush border. The intercellular material
      was changed in structure, showing increased electron density in some areas and
      oedema of the intercellular spaces in other areas. There were also fractures of
      the tegument of variable depth, sometimes reaching to the parenchyma. These
      results suggest altered tegumental integrity and, occasionally, complete
      disruption of the selective permeability barrier created by the normal tegument.
      This suggestion is further supported by the penetration of ruthenium red into
      some tegumental areas and its distribution into the intercellular spaces, down to
      the parenchyma. The intrategumental lysosomes also appeared to be significantly
      activated. There was evidence of autophagy in both distal cytoplasm and
      tegumental cells. Mature and gravid proglottides were more susceptible to drug
      damage than those in the anterior strobila and neck.

PMID- 1377378
TI  - Cross-bridge stiffness in Ca(2+)-activated skinned single muscle fibres.
AB  - Tension transients, in response to small and rapid length changes (completed
      within 40 microseconds), were obtained from skinned single frog muscle fibres
      incubated in activating solutions with varying concentrations of Ca2+. The first
      2 ms of these transients were described by a linear model in which the fibre is
      regarded as a rod composed of infinitesimally small, identical segments
      containing a mass, one undamped elastic element and in the case of relaxed fibres
      two damped elastic elements in series, or in the case of activated fibres three
      such elastic elements in series. The stiffness of activated fibres, expressed in
      elastic constants or apparent elastic constants, increased with increasing
      concentrations of Ca2+. All the damped elastic constants that were necessary to
      describe the tension responses of activated fibres were proportional to isometric
      tension. However, the undamped elastic constant did not increase linearly with
      increasing isometric tension. Equatorial X-ray diffraction patterns were obtained
      from single frog muscle fibres under similar conditions as under which the
      tension transients were obtained. The filament spacing (d10) of Ca(2+)-activated
      single frog muscle fibres decreased with increasing isometric force, whereas the
      intensity ratio (I11/I10) increased linearly with increasing isometric force.
      From experiments in which dextran (MW 200,000 Da) was added, it followed that
      such a change in filament spacing would modify passive stiffness. The d10 value
      of relaxed fibres decreased and stiffness increased with increasing
      concentrations of the polymer dextran, whereas I11/I10 remained constant. The
      relation of stiffness and filament spacing with concentration of dextran was used
      to eliminate the effect of decreased filament spacing on stiffness of activated
      fibres. After correction for changes in filament spacing the undamped complicance
      C1, normalized to tension, was not constant, but increased with increasing
      isometric tension. If we assume that isometric tension is proportional to the
      number of force generating cross-bridges, this means that only part of the
      undamped compliance of activated fibres is located in the cross-bridges.

PMID- 1377376
TI  - A small-conductance charybdotoxin-sensitive, apamin-resistant Ca(2+)-activated K+
      channel in aortic smooth muscle cells (A7r5 line and primary culture).
AB  - A small conductance K+ channel was identified in smooth muscle cells of the rat
      aortic cell line A7r5 and also in rat aortic smooth muscle cells in primary
      culture, using conventional single-channel recording techniques. The single
      channel conductance shows no rectification, either in the range -70 to +40 mV
      under asymmetrical conditions (9.1 pS), or in the range -100 to +50 mV in
      symmetrical 150 mM K+ (37 pS). Channel activity is reversibly inhibited by
      extracellular application of charybdotoxin, with a concentration of 8 nM
      producing half-maximal inhibition. It is unaffected by apamin or scyllatoxin.
      Channel activity depends on the presence of free Ca2+ on the cytosolic face of
      the membrane, with an activation zone between 0.1 and 1 microM. This small
      conductance, charybdotoxin-sensitive, Ca(2+)-regulated K+ channel is activated by
      vasoconstrictors such as vasopressin and endothelin.

PMID- 1377377
TI  - Paradoxical decrease in cytosolic calcium with increasing depolarization by
      potassium in guinea-pig mesotubarium smooth muscle.
AB  - The free intracellular Ca2+ concentration ([Ca2+]i) was measured simultaneously
      with isometric force in strips of guinea-pig mesotubarium using the Fura-2
      technique. [Ca2+]i and force were maximal at a relatively low (30 mM)
      concentration of extracellular K+ ([K+]o), and declined at 90 and 140 mM K+.
      Plateau values of both [Ca2+]i and force were higher in the presence of 5.10(-6)
      M ryanodine, indicating that the sarcoplasmic reticulum (SR) contributes to the
      decline with depolarization. Force and [Ca2+]i at 90 mM K+ were both lower then
      the high-K+ solution was applied after a period in 30 mM K+ than after a period
      in normal solution (5.9 mM K+), consistent with inactivation of Ca2+ channels
      during prolonged depolarization. Addition of carbachol to the depolarized muscle
      caused a maintained increase in force without maintained increase in [Ca2+]i. We
      conclude that the decrease in force at increased [K+]o (the "calcium-potassium
      paradox") is due to a membrane-potential-mediated decrease in [Ca2+]i and, to a
      lesser extent, to desensitization of the contractile-regulatory apparatus to
      Ca2+.

PMID- 1377379
TI  - Determinants for binding of a 40 kDa protein to the leaders of yeast
      mitochondrial mRNAs.
AB  - An abundant yeast mitochondrial 40 kDa protein (p40) binds with high specificity
      to the 5'-untranslated region of cytochrome c oxidase subunit II (COX2) mRNA.
      Using mobility shift and competition assays, we show here that purified p40
      complexes with the leaders of all eight mitochondrial mRNAs of Saccharomyces
      cerevisiae. The location of the protein binding site on the different leaders is
      not conserved with respect to the AUG start codon. In vitro RNA footprint and
      deletion experiments have been used to define the p40-binding site on the leaders
      of COX1 and ATP9 mRNAs. Nucleotides at, and near, a single stranded region are
      protected or exposed for DEPC modification by binding of p40 to these leaders.
      Removal of this region from the COX1 messenger shows that it is essential for the
      protein-RNA interaction. While no obvious sequence similarity can be detected
      between the single stranded regions in different leaders, a nearby helical
      segment is conserved. A consensus model for p40-RNA interactions is presented and
      the possible biological function of p40 is discussed.

PMID- 1377380
TI  - Extensive phosphorothioate substitution yields highly active and nuclease
      resistant hairpin ribozymes.
AB  - The catalytic function of the hairpin ribozyme has been investigated by
      modification-interference analysis of both ribozyme and substrate, using
      ribonucleoside phosphorothioates. Thiophosphate substitutions in two ribozyme
      domains were examined by using a novel and highly efficient two-piece ribozyme
      assembled from two independently synthesized oligoribonucleotides. The catalytic
      proficiency of the two-piece construct (KM = 48 nM, kcat = 2.3 min-1) is nearly
      identical to that of the one-piece ribozyme. The two-piece ribozyme is
      essentially unaffected by substitution with thiophosphates 5' to all guanosines,
      cytidines, and uridines. In contrast, incorporation of multiple adenosine
      phosphorothioates in the 5' domain of the ribozyme decreases ribozyme activity by
      a factor of 25. Modification-interference experiments using ribozymes partially
      substituted with adenosine phosphorothioate suggest that thiophosphates 5' to A7,
      A9 and A10 interfere with cleavage to a greater extent than substitutions at
      other sites within the molecule, but the effect is modest. Within the substrate,
      phosphorothioate substitution does not directly interfere with cleavage, rather,
      increasing thiophosphate content decreases the stability of the ribozyme
      substrate complex. We describe the construction of a hairpin ribozyme containing
      dinucleotide extensions at its 5' and 3' ends. Full substitution of this molecule
      with G and C phosphorothioates results in a ribozyme with greatly enhanced
      stability against cellular ribonucleases without significant loss of catalytic
      efficiency.

PMID- 1377381
TI  - Competition of aminoacyl-tRNA synthetases for tRNA ensures the accuracy of
      aminoacylation.
AB  - The accuracy of protein biosynthesis rests on the high fidelity with which
      aminoacyl-tRNA synthetases discriminate between tRNAs. Correct aminoacylation
      depends not only on identity elements (nucleotides in certain positions) in tRNA
      (1), but also on competition between different synthetases for a given tRNA (2).
      Here we describe in vivo and in vitro experiments which demonstrate how
      variations in the levels of synthetases and tRNA affect the accuracy of
      aminoacylation. We show in vivo that concurrent overexpression of Escherichia
      coli tyrosyl-tRNA synthetase abolishes misacylation of supF tRNA(Tyr) with
      glutamine in vivo by overproduced glutaminyl-tRNA synthetase. In an in vitro
      competition assay, we have confirmed that the overproduction mischarging
      phenomenon observed in vivo is due to competition between the synthetases at the
      level of aminoacylation. Likewise, we have been able to examine the role
      competition plays in the identity of a non-suppressor tRNA of ambiguous identity,
      tRNA(Glu). Finally, with this assay, we show that the identity of a tRNA and the
      accuracy with which it is recognized depend on the relative affinities of the
      synthetases for the tRNA. The in vitro competition assay represents a general
      method of obtaining qualitative information on tRNA identity in a competitive
      environment (usually only found in vivo) during a defined step in protein
      biosynthesis, aminoacylation. In addition, we show that the discriminator base
      (position 73) and the first base of the anticodon are important for recognition
      by E. coli tyrosyl-tRNA synthetase.

PMID- 1377382
TI  - A plant virus satellite RNA exhibits a significant sequence complementarity to a
      chloroplast tRNA.

PMID- 1377383
TI  - Nucleotide sequence of a satellite RNA of a strain of cucumber mosaic virus
      associated with a tomato fruit necrosis.

PMID- 1377384
TI  - Can early bacterial complications of aspiration with respiratory failure be
      predicted?
AB  - We studied the early infectious complications of all children admitted for
      intensive care over a six-year period who were at high risk of having severe
      aspiration of gastric or pharyngeal secretions. Patients were only analyzed if
      they required mechanical ventilation for acute respiratory failure, had a blood
      culture obtained in the first 48 hours, and survived at least 24 hours.
      Infections were identified by positive blood cultures. Possible infections were
      defined as fever (over 38.5 degrees C), abnormal leukocyte count (greater than
      10,000 or less than 5000), and a potential pathogen in tracheal secretions.
      Patients' diagnoses included near-drowning (13), aspirated foreign body (5),
      observed aspiration of gastric contents in a hospitalized patient (2), and
      hydrocarbon aspiration (1). Of 21 high-risk patients, five (23.8%) had infections
      and two (9.5%) had possible infections in the first 48 hours. In contrast, no
      late infections were seen. Infected patients tended to be older (P less than
      0.05). No diagnostic features in the first two days of hospitalization reliably
      identified those who would develop early infections (P greater than 0.05). Since
      early life-threatening infection is common and cannot be reliably predicted by
      clinical signs, we recommend aggressive bacteriologic surveillance and the
      administration of IV antibiotics on admission to all patients in respiratory
      failure requiring mechanical ventilation after presumed aspiration of gastric or
      pharyngeal secretions.

PMID- 1377385
TI  - Inducing tricuspid regurgitation as palliation.
AB  - We describe a technique for palliative decompression of the hypertensive right
      ventricle seen in pulmonary atresia with intact ventricular septum (PAIVS),
      utilizing a bioptome catheter for partial tricuspid avulsion.

PMID- 1377386
TI  - Prostate cancer. Finding and managing it.
AB  - Despite development of new technology for the diagnosis and treatment of prostate
      cancer, the age-adjusted mortality rate for the disease has not declined for
      nearly half a century. Physicians now have the ability to diagnose very small
      tumors in asymptomatic patients, but it remains to be determined which subset of
      patients would benefit most from early identification and treatment. Studies that
      are currently under way hopefully will clarify what screening protocols, if any,
      actually reduce the mortality and morbidity that are associated with prostate
      cancer and its treatment. Until such evidence becomes available, screening
      measures for the general population are unwarranted, with the possible exception
      of digital rectal examination performed as part of other healthcare services.
      Prostate-specific antigen (PSA) determination may have a place in screening
      patients whose family history puts them at increased risk. In patients with
      symptoms or findings suggestive of prostate cancer, diagnosis and staging can be
      accomplished more accurately and easily than ever before with a combination of
      PSA determination, transrectal ultrasound, ultrasound-guided tissue sampling
      using a biopsy gun, and the judicious use of imaging techniques such as bone
      scans, magnetic resonance imaging, and computed tomography. New treatment methods
      are being studied, and the options available, especially for management of
      disease progression, are expected to increase. Monitoring of treated patients has
      been greatly facilitated by determination of PSA levels, which are predictive of
      both long- and short-term prognosis. Although much work remains to be done, we
      may finally be on the verge of making real progress in control of prostate
      cancer.

PMID- 1377387
TI  - Testicular cancer. Role of primary care physicians in screening and education.
AB  - Cure rates for testicular cancer have improved dramatically over the years, but
      early diagnosis is still essential. Primary care physicians have a responsibility
      to include testicular examination as part of cancer screening and to educate
      young male patients about the frequency of testicular cancer in their age-group
      and on how to perform self-examination. A high index of suspicion and careful
      bimanual palpation are crucial in evaluation of complaints referable to the
      scrotum. Prompt urologic consultation must be obtained if a tumor is suspected.

PMID- 1377388
TI  - Improved performance in a prenatal screening programme for Down's syndrome
      incorporating serum-free hCG subunit analyses.
AB  - A prenatal screening programme for Down's syndrome potentially detecting 76 per
      cent of affected pregnancies in the South Australian general population at an
      amniocentesis rate of 3.9 per cent was designed following analysis of mid
      trimester serum samples from 57 women who carried an affected fetus. This equates
      to one affected pregnancy being detected for 41 chromosomal analyses performed.
      For the experimental series, 75.4 per cent of affected pregnancies were detected,
      while 4.1 per cent of control specimens produced estimated risk odds consistent
      with further action. A maternal risk odds of birth of a Down's syndrome fetus of
      1:420 was taken as the decision value, which is the prevalence of Down's syndrome
      births to 35-year-old mothers in South Australia. This screening performance was
      achieved by investigating combinations of serum analytes not previously reported
      and by refining the calculation of maternal risk odds to include selective
      weighting of indicator analytes. Combination of the measurements of free alpha
      subunits and beta-subunits of chorionic gonadotrophin, alpha-fetoprotein,
      unconjugated oestriol, and placental lactogen was found to be most effective in
      indicating Down's syndrome fetuses. In all combinations of analytes tested,
      replacing the measurements of free alpha-subunits and free beta-subunits of
      chorionic gonadotrophin with the measurement of intact chorionic gonadotropin
      produced a less effective screen.

PMID- 1377389
TI  - Maternal serum alpha-fetoprotein levels and fetal outcome in early second
      trimester oligohydramnios.
AB  - Early second-trimester oligohydramnios was associated with normal maternal serum
      alpha-fetoprotein (MSAFP) levels in nine out of 26 cases (35 per cent).
      Congenital malformations of the fetal urinary tract resulting in fetal anuria
      were present in nine cases; in seven of them, normal MSAFP levels were measured.
      In contrast, normal MSAFP levels were established in only 2 out of the 17 cases
      without fetal malformations. These data suggest that fetal urine is the major
      source of elevated AFP in the maternal compartment in early second-trimester
      oligohydramnios. This is further supported by the lack of any relationship
      between concentrations of MSAFP non-reactive with Concanavalin A, originating
      mainly from the yolk sac-derived amniotic fluid AFP pool, and the presence of
      fetal diuresis. Three out of 26 women had experienced early second-trimester
      oligohydramnios in a previous pregnancy, suggesting the existence of a recurrence
      risk for this condition.

PMID- 1377390
TI  - High levels of maternal serum alpha-fetoprotein and human chorionic
      gonadotrophins leading to the diagnosis of combined neural tube defect and
      partial mole.
AB  - A case of combined partial mole and neural tube defect is presented. The
      detection of high levels of both maternal serum (MS) alpha-fetoprotein (AFP) and
      human chorionic gonadotrophin (hCG) during the second trimester led to the
      ultrasonic demonstration of anencephaly, omphalocele, and partial mole. This is
      the first report of combined elevation of MSAFP and MShCG.

PMID- 1377391
TI  - Maternal serum alpha-fetoprotein in the first trimester cannot predict neural
      tube defects.

PMID- 1377392
TI  - Soluble T lymphocyte antigen-specific molecules.

PMID- 1377394
TI  - Pericranial healing and the temporalis myo-osseous flap in the rabbit model.
AB  - The purpose of this animal study was to determine the rate of revascularization
      of a temporalis myo-osseous (TMO) flap after pericranial elevation. In 24
      rabbits, the right pericranium was raised in entirety through a bicoronal flap at
      the first operation. The pericranium was then reapproximated in situ. The
      pericranium was allowed to heal for 1 to 28 days before the second operation. At
      the second operation, through the same bicoronal flap, right and left temporalis
      myo-osseous flaps were raised. The left temporalis myo-osseous flap served as a
      control. Revascularization and viability of the temporalis myo-osseous flaps were
      studied by using technetium bone scans, india ink injection studies, and
      histologic study. Results demonstrated that 4 days following pericranial
      elevation, the temporalis myo-osseous flap is viable and revascularized by the
      pericranium. Immediate bone scanning and india ink injection showed patent
      pericranial circulation to the osseous portion of the temporalis myo-osseous flap
      at 4 days. Histologic study confirmed the viability of the temporalis myo-osseous
      flap. In conclusion, after pericranial elevation, pericranial healing and
      revascularization were complete at 4 days. This allowed a viable temporalis myo
      osseous flap to be raised successfully at this time.

PMID- 1377393
TI  - Interleukin 4 induces the maturation of idiotype-specific regulatory B cell
      populations.
AB  - CD5+ B cells have been shown to be disproportionately associated with autoimmune
      diseases and transformation. In many cases, their apparent ability to bypass self
      tolerance is manifested by the production of autoantibodies. These observations,
      plus the hypothesis that CD5+ B cells represent a distinct B cell lineage,
      encourage studies into the conditions and factors that influence their
      development. In the present study, we employed a well-established assay for
      murine CD5+ B cell function, i.e., their ability to augment the responses of IgHb
      linked idiotypic determinants on anti-(4-hydroxy-3-nitrophenyl) acetyl (NP)
      antibody (Nbb) idiotype-bearing CD5- B cells to a T-independent antigen, together
      with multiple methods of cell surface phenotyping, to evaluate the potential for
      interleukin (IL) 4 to effect maturation of CD5+ B cells, CD5+, IgM+, Thy-1-, and
      NPb idiotype-specific cells panned on antibody-coated petri dishes or sorted by
      flow cytometry from spleen were capable of augmenting NPb idiotypic responses of
      NP-KLH-primed responder cells to NP-Ficoll. Splenic B cell populations depleted
      of CD5+ B cells failed to affect idiotype expression even after 2 days in
      culture, a time when a small percentage of CD5+ B cells appeared to be
      regenerated. However, idiotype-specific regulatory activity could be restored in
      CD5- splenic B cell populations by culture for 2 days with recombinant IL-4.
      Cells responsible for idiotype-specific regulatory activity after culture with IL
      4 were in fact CD5+, IgM+, and Thy-1.2- B cells, demonstrating that IL-4 can
      drive the functional, if not the phenotypic, maturation of splenic B cells
      associated with the CD5+ B cell lineage. The results illustrate one possible
      mechanism by which T cells could control the maturation of cells belonging to the
      CD5+ B cell lineage.

PMID- 1377395
TI  - Stereoselective behavioral effects of Lu 19-005 in monkeys: relation to binding
      at cocaine recognition sites.
AB  - The effects of the monoamine uptake inhibitor Lu 19-005 ((+/-)-trans-3-(3,4
      dichlorophenyl)-N-methyl-1-indanamine) and its (+) and (-) enantiomers, Lu 20-042
      and Lu 20-043, were compared with those of cocaine and the selective dopamine
      uptake inhibitor GBR 12909 (1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3
      phenylpropyl)piperazine) in behavioral and radioligand binding experiments.
      Behavioral experiments were conducted in groups of squirrel monkeys trained under
      fixed-interval schedules of reinforcement in which responding was maintained
      either by presentation of food or by termination of a visual stimulus associated
      with mild electric shock. Radioligand binding studies were conducted using
      [3H]CFT and [3H]GBR 12935 to label elements of the dopamine uptake system in
      caudate-putamen membranes of cynomolgus monkeys. All drugs produced dose-related
      increases in response rate under the fixed-interval schedules. Lu 19-005, Lu 20
      042, and Lu 20-043 had relatively slow onsets (approximately 2 h) and relatively
      long durations of action, with effects persisting for two or more days following
      administration. Stereoselectivity was evident in the behavioral effects of the
      enantiomers of Lu 19-005, with Lu 20-042 being approximately 14 times more potent
      than Lu 20-043. In radioligand binding experiments, Lu 19-005 and its enantiomers
      were potent inhibitors of specifically bound [3H]CFT and [3H]GBR 12935. As in
      behavioral experiments, Lu 20-042 was more potent than Lu 20-043. The degree of
      stereoselectivity, however, varied with the temperature of the assay
      medium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377396
TI  - Impaired acquisition of temporal differentiation performance following lesions of
      the ascending 5-hydroxytryptaminergic pathways.
AB  - Nineteen rats received injections of 5,7-dihydroxytryptamine into the dorsal and
      median raphe nuclei; 16 rats received sham injections. The rats underwent 50
      daily training sessions under an interresponse-time-greater-than-15-seconds (IRT
      greater than 15 s) schedule of sucrose reinforcement. The lesioned group showed
      impaired acquisition of temporal differentiation, in that their response rates
      remained significantly higher and their obtained reinforcement frequencies
      significantly lower than those of the control (sham-lesioned) group. Comparison
      of the IRT frequency distributions obtained from the two groups during the last 5
      days of training showed that the lesioned group produced a significantly higher
      proportion of very short IRTs (less than 3 s) than the control group; when these
      short IRTs were disregarded, the lesioned group displayed a significantly lower
      mean IRT and a significantly higher coefficient of variation than the control
      group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in
      the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus
      were markedly reduced in the lesioned group, but the levels of noradrenaline and
      dopamine were not significantly affected by the lesion. The results suggest that
      destruction of the ascending 5HTergic pathways may reduce animals' capacity to
      inhibit positively reinforced operant behaviour, and may impair temporal
      discrimination.

PMID- 1377397
TI  - The clinical effectiveness of self-injection and external vacuum devices in the
      treatment of erectile dysfunction: a six-month comparison.

PMID- 1377398
TI  - The indispensable CD2-CD3 molecules: a key to T-cell differentiation and
      functional activation.

PMID- 1377399
TI  - Human umbilical vein endothelial cells synthesize S-protein (vitronectin) in
      vitro.
AB  - S-protein, also named vitronectin, is a multifunctional glycoprotein with
      molecular weight (MW) of about 75 kDa and a serum concentration of 0.14-0.60
      mg/ml. It is synthesized mainly in the liver, but synthesis has also been found
      in monocytes/macrophages. We used human umbilical vein endothelial cells (EC)
      which were incubated with agarose beads, an activator of the alternative
      complement pathway. By radioimmunoassay (RIA) based on monoclonal and polyclonal
      S-protein antibodies, we detected S-protein on harvested agarose beads. The time
      dependent increase in the amount of S-protein was significantly reduced by the
      presence of cycloheximide (10 micrograms/ml) in the cell cultures. We also found
      a strong binding of S-protein antibodies to agarose beads preincubated in native
      serum, which was strongly reduced (70-80%) by inactivation of the alternative
      complement pathway (50 degrees C, 20 min). Our results show that EC synthesize S
      protein in vitro.

PMID- 1377400
TI  - Reactivity and self-association in vivo of a human monoclonal IgG rheumatoid
      factor.
AB  - In order to study the pathogenic potential of IgG rheumatoid factor (IgG-RF) we
      generated a human monoclonal IgG4-RF-producing cell line, OR-1, by Epstein-Barr
      virus transformation of B cells derived from a healthy donor. Characterization of
      OR-1 RF specificity demonstrated that this RF binds only to IgG and not to dsDNA
      or seven different proteins tested. Although both OR-1 RF and C1q bind to the Fc
      part of IgG, no influence could be observed of OR-1 RF on the complement-fixing
      potential of heat-aggregated IgG, suggesting that OR-1 RF does not interfere with
      C1q binding to IgG. This was confirmed by blocking studies which showed that
      binding of OR-1 RF to IgG could be prevented by Staphylococcal protein A (SpA),
      but not by C1q. Comparison of OR-1 RF with SpA regarding their ability to bind to
      IgG derived from different species and human IgG subclasses demonstrated that OR
      1 RF and SpA have an identical IgG specificity. The possibility that a structural
      homology exists between SpA and OR-1 RF was ruled out, however, by using affinity
      purified chicken anti-SpA antibodies, which were not able to bind to OR-1 RF. The
      potential of self-recognition of OR-1 RF in vivo was examined by injecting OR-1
      cells in SCID mice. Two months after injection IgG-RF was present in the
      circulation in monomeric, dimeric and polymeric forms whereas circulating IgG
      without RF activity, derived from an injected control cell line, was present in
      the monomeric form only. In vitro studies indicated that IgG-RF is secreted in
      monomeric form and that polymerization is a concentration-dependent phenomenon.
      The fact that IgG-RF is able to form immune complexes in vivo indicates that IgG
      RF has a pathogenic potential by itself and therefore IgG-RF may play a role in
      the pathogenesis of RA.

PMID- 1377401
TI  - [Assessment of the nephrotoxicity of amikacin in patients with cystic fibrosis].
AB  - Cystic fibrosis patients are at risk for nephrotoxic effects of aminoglycosides.
      Fifteen cystic fibrosis patients were admitted to hospital with 18 acute
      exacerbations of pulmonary symptoms associated with the isolation of Pseudomonas
      aeruginosa from sputum. They were treated intravenously with amikacin and
      ceftazidime for 14 days. Urinary excretion of N-acetyl-beta-D-glucosaminidase and
      alpha 1-microglobulin, two markers of tubular damage, and of albumin, a marker of
      glomerular permeability, was studied before and during treatment. Urinary
      activity of N-acetyl-beta-D-glucosaminidase and excretion of alpha 1
      microglobulin was normal before amikacin treatment in approximately two thirds of
      patients and pathologically increased at the end of the study in 95%. Urinary
      albumin excretion was always normal before amikacin treatment and failed to
      increase consistently during treatment. The pattern of urinary protein excretion
      observed in the study before and during treatment with amikacin indicates a
      selective tubular toxicity.

PMID- 1377402
TI  - Another piece of the HIV puzzle falls into place.

PMID- 1377403
TI  - Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed
      with an inhibitor.
AB  - A 3.5 angstrom resolution electron density map of the HIV-1 reverse transcriptase
      heterodimer complexed with nevirapine, a drug with potential for treatment of
      AIDS, reveals an asymmetric dimer. The polymerase (pol) domain of the 66
      kilodalton subunit has a large cleft analogous to that of the Klenow fragment of
      Escherichia coli DNA polymerase I. However, the 51-kilodalton subunit of
      identical sequence has no such cleft because the four subdomains of the pol
      domain occupy completely different relative positions. Two of the four pol
      subdomains appear to be structurally related to subdomains of the Klenow
      fragment, including one containing the catalytic site. The subdomain that appears
      likely to bind the template strand at the pol active site has a different
      structure in the two polymerases. Duplex A-form RNA-DNA hybrid can be model-built
      into the cleft that runs between the ribonuclease H and pol active sites.
      Nevirapine is almost completely buried in a pocket near but not overlapping with
      the pol active site. Residues whose mutation results in drug resistance have been
      approximately located.

PMID- 1377405
TI  - Isolation of primitive hematopoietic stem cells.

PMID- 1377404
TI  - Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand
      CD59.
AB  - The interaction of the T cell glycoprotein CD2 with one ligand, CD58, contributes
      to T cell function. We have identified CD59, a glycoprotein with complement
      inhibitory function, as a second physiological ligand for CD2. Antibodies to CD59
      inhibit CD2-dependent T cell activation in murine T cell hybridomas expressing
      human CD2. In an in vitro binding assay with purified CD58 and CD59, CD2+ cells
      bind not only immobilized CD58 but also CD59. With two complementary approaches,
      it was demonstrated that the binding sites on CD2 for CD58 and CD59 are
      overlapping but nonidentical. These observations suggest that direct interactions
      between CD2 and both CD58 and CD59 contribute to T cell activation and adhesion.

PMID- 1377406
TI  - Stem cell selection for autologous bone marrow transplantation.

PMID- 1377407
TI  - [Conjugate vaccines against bacterial infections: typhoid fever].
AB  - Capsular polysaccharides have been studied as possible vaccines against
      infectious diseases. However, they are capable to induce only short-run
      protection because of their T-independent properties and they would not be
      protective against infection in high-risk populations. The alternative to face
      this problem is to develop methods to join covalently the polysaccharide and
      proteins to both increase the immunogenicity of and to confer the property of T
      dependence to this antigen. In order to obtain a conjugate vaccine against
      typhoid fever, in our laboratory we have tried to synthesize a conjugate
      immunogen between the Vi antigen and porins from Salmonella typhi.

PMID- 1377408
TI  - [Development of oral vaccines based on recombinant proteins derived from cholera
      toxin].
AB  - In this paper a new approach to create antigens through genetic engineering is
      discussed. In this particular case the subunits of V. cholerae toxin are used as
      heterologous epitope carries. In this paper the manipulation of A and B subunits
      is described. This manipulation allows both the insertion of epitopes to the B
      subunit and the use of subunit A in the construction of recombinant antigens
      similar to the ones derived from subunit B.

PMID- 1377409
TI  - Primary yolk sac tumor of the cerebellar vermis: case report.
AB  - A rare case of yolk sac tumor in the cerebellar vermis is reported. A 2-year-old
      boy developed headaches, vomiting, and an unsteady gait. Later a tumor was
      demonstrated in the medial part of the cerebellum by gadolinium-enhanced magnetic
      resonance imaging (MRI). The tumor was totally removed, and the surgery was
      followed by chemotherapy. Soon after surgery the elevated alphafetoprotein (AFP)
      levels in the serum and cerebrospinal fluid were observed to decrease to normal
      levels. Three months later enhanced MRI showed a lesion in the vermis without any
      elevation of AFP, and the lesion turned out to be a granuloma. Six months after
      the second surgery a tumor recurred that could not be totally removed. Cranial
      radiotherapy was given together with chemotherapy, which resulted in a decrease
      of AFP to the normal range. The patient is doing well without any elevation in
      AFP at 1 year 6 months after onset. Related problems in the diagnosis and
      treatment of yolk sac tumors are discussed.

PMID- 1377410
TI  - [Outpatient--safe patients].

PMID- 1377411
TI  - Valproic acid-induced spina bifida: a mouse model.
AB  - Prenatal exposure to the antiepileptic drug valproic acid (VPA) has been
      associated with the formation of spina bifida aperta, meningocele, and
      meningomyelocele in the human. Until now, a direct relationship between VPA
      application and spina bifida has not been experimentally demonstrated. VPA was
      known only to induce exencephaly in mice, a defect of the anterior neural tube.
      Maximal sensitivity toward production of this defect was on day 8 of gestation
      (plug day = day 0). The closure of the posterior neuropore occurs later in the
      development of mice than the closure of the anterior neuropore. To investigate
      whether there is a direct relationship between VPA application during pregnancy
      and induction of spina bifida in mice, we administered various doses of the drug
      on day 9 of gestation, at three time intervals (at 0, 6, and 12 hr). This
      administration of VPA produced spina bifida aperta and spina bifida occulta in
      mice. High doses of VPA (3 x 450 and 3 x 500 mg/kg) induced a low rate of spina
      bifida aperta in the lumbosacral region. High incidences of spina bifida occulta,
      a less serious form of spina bifida, were induced with lower doses. This
      malformation was demonstrated in double-stained fetal skeletons by measurements
      of the distance between the cartilaginous ends of each vertebral arch. The
      occurrence of this defect and its localization was dose-dependent. The lumbar
      region was affected by all doses investigated (3 x 300, 3 x 350, 3 x 400, 3 x
      450, and 3 x 500 mg/kg). The sacral/coccygeal region was affected additionally,
      but with higher doses (3 x 400, 3 x 450, and 3 x 500 mg/kg). A comparison of the
      results obtained with day 16 and 17 control fetuses showed that the pattern of
      gaps present in the lumbar and sacral region of the spinal cord in treated groups
      was drug-specific and not related to a developmental delay. Our results indicate
      that multiple administrations of VPA on day 9 of gestation in mice result in a
      low incidence of spina bifida aperta and a high incidence of spina bifida
      occulta, and provides a relevant model for the study of human spina bifida
      defects.

PMID- 1377412
TI  - Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative
      assessment of plasmin-alpha 2-antiplasmin complex with a novel monoclonal
      antibody based radioimmunoassay.
AB  - Infusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in
      plasma plasminogen activator activity. Whether this increase results in the
      generation of plasmin in vivo has never been established. A novel sensitive
      radioimmunoassay (RIA) for the measurement of the complex between plasmin and its
      main inhibitor alpha 2-antiplasmin (PAP complex) was developed using monoclonal
      antibodies preferentially reacting with complexed and inactivated alpha 2
      antiplasmin and monoclonal antibodies against plasmin. The assay was validated in
      healthy volunteers and in patients with an activated fibrinolytic system.
      Infusion of DDAVP in a randomized placebo controlled crossover study resulted in
      all volunteers in a 6.6-fold increase in PAP complex, which was maximal between
      15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP
      complex decreased with an apparent half-life of disappearance of about 120 min.
      Infusion of DDAVP did not induce generation of thrombin, as measured by plasma
      levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.
      We conclude that the increase in plasminogen activator activity upon the infusion
      of DDAVP results in the in vivo generation of plasmin, in the absence of
      coagulation activation. Studying the DDAVP induced increase in PAP complex of
      patients with thromboembolic disease and a defective plasminogen activator
      response upon DDAVP may provide more insight into the role of the fibrinolytic
      system in the pathogenesis of thrombosis.

PMID- 1377413
TI  - Neutralization of the antiheparin activity of platelet factor 4 by a monoclonal
      antibody.
AB  - We have produced a panel of monoclonal antibodies (mAbs) against rabbit platelet
      factor 4 (PF4). Two of these mAbs have been characterized in this study. In
      particular the antibody called 10B2, which also recognizes the human molecule, is
      able to block PF4's ability to neutralize heparin in a modified Heparin-Factor Xa
      chromogenic assay. The inhibition appears to be more than 95% at 1:1 mAb/PF4
      molar ratio both for purified rabbit and human PF4. Similar results were obtained
      using supernatants from stimulated human platelets (90% of inhibition at 1:1
      mAb/PF4 molar ratio) or using Fab fragments from 10B2. Studies to determine the
      antigenic determinant against which 10B2 is directed, show that this is an
      assembled epitope which involves disulfide bonds of the PF4.

PMID- 1377414
TI  - Fine mapping of monoclonal antibody epitopes on human von Willebrand factor using
      a recombinant peptide library.
AB  - A recombinant human von Willebrand factor (vWF) cDNA fragment library was
      constructed in lambda gt11 for the localization of anti-vWF monoclonal antibody
      epitopes. Twelve of 21 monoclonal antibodies screened identified epitopes
      expressed in lambda gt11 as beta-galactosidase fusion proteins. By sequence
      analysis, these antigenic determinants were localized to segments ranging from 17
      to 105 amino acids in length. Four epitopes apparently shared by more than one
      antibody were identified, suggesting the presence of immuno-dominant epitopes
      within vWF. Monoclonal antibody C3, which blocks factor VIII (FVIII) binding to
      vWF, bound to the same epitope previously identified by a second monoclonal
      antibody which also blocks this function, suggesting that this region may be at
      or near the vWF/FVIII binding domain. Three antibodies recognize the same region
      within the vWF A2 repeat. Mutations near this region appear to be responsible for
      Type IIA von Willebrand's disease. The co-localization of these antibodies
      suggests that this domain might be exposed on the surface of vWF, consistent with
      its apparent increased sensitivity to plasma proteases.

PMID- 1377415
TI  - Aprotinin does not inhibit the release of PGI2 or vWF from cultured human
      endothelial cells.
AB  - The release of prostacyclin (PGI2) and von Willebrand factor (vWF) from human
      umbilical vein endothelial cells (HUVEC) was examined to determine if aprotinin
      had any effects on these endothelial cell reactions. These end-points were chosen
      to indicate if this serine protease inhibitor caused alterations in the control
      of haemostatic function by endothelium, in the light of the improvement in
      haemostasis seen in patients given aprotinin therapy at the time of open heart
      surgery. Stimuli used to promote secretion of prostacyclin and vWF were human
      alpha-thrombin, histamine, protamine sulphate, poly-L-lysine and phorbol
      myristate acetate. Aprotinin (30 microMs) had no significant effect on the basal
      or stimulated release of PGI2 or vWF from HUVEC.

PMID- 1377416
TI  - Characterization of human tissue-type plasminogen activator with monoclonal
      antibodies: mapping of epitopes and binding sites for fibrin and lysine.
AB  - The study defines interactions between human tissue-type plasminogen activator (t
      PA) and 21 mouse monoclonal antibodies (mAb). Characterization includes epitope
      distribution, reactivity of different forms of t-PA with antibodies, and
      modification of t-PA function by antibody binding. Eighteen antibodies are
      directed against t-PA A-chain. These antibodies recognize four distinct epitopes
      (A, B, C, D) and one partially overlapping epitope (D'). The remaining three
      antibodies are directed against two different epitopes (E, F) on catalytically
      active t-PA B-chain. A-chain reactive antibodies do not bind to the reduced form
      of t-PA, while B-chain reactive antibodies bind to reduced and deglycosylated t
      PA forms. The latter antibodies associate more tightly with sc t-PA than with tc
      t-PA and have a higher affinity for t-PA-PAI 1 complex as compared to free t-PA.
      The analysis of functional effects of antibodies reveals that antibodies directed
      against all above defined epitopes inhibit interactions between t-PA and fibrin:
      a) binding of t-PA to fibrin, b) fibrinolytic activity of t-PA, and c) fibrin
      activation of sc t-PA amidolytic activity. The observations support the
      assumption that several sites of t-PA are involved in fibrin binding and that
      fibrin-bound t-PA is closely surrounded by the fibrin mesh. Many antibodies
      quench also binding of t-PA to lysine-Sepharose. Experiments with free, non-fixed
      lysine confirm strong competition between lysine and mAb 16 and 18, directed
      against epitope A, and mAb 29, binding to epitope F.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377417
TI  - An enzyme-linked immunosorbent assay for urokinase-type plasminogen activator (u
      PA) and mutants and chimeras containing the serine protease domain of u-PA.
AB  - An enzyme-linked immunosorbent assay (ELISA) for quantitation of natural and
      recombinant plasminogen activators containing the serine protease domain (B
      chain) of urokinase-type plasminogen activator (u-PA) was developed, based on two
      murine monoclonal antibodies, MA-4D1E8 and MA-2L3, raised against u-PA and
      reacting with non-overlapping epitopes in the B-chain. MA-4D1E8 was coated on
      microtiter plates and bound antigen was quantitated with MA-2L3 conjugated with
      horseradish peroxidase. The intra-assay, inter-assay and inter-dilution
      coefficients of variation of the assay were 6%, 15% and 9%, respectively. Using
      recombinant single-chain u-PA (rscu-PA) as a standard, the u-PA-related antigen
      level in normal human plasma was 1.4 +/- 0.6 ng/ml (mean +/- SD, n = 27). The
      ELISA recognized the following compounds with comparable sensitivity: intact scu
      PA (amino acids, AA, 1 to 411), scu-PA-32k (AA 144 to 411), a truncated (thrombin
      derived) scu-PA comprising AA 157 to 411, and chimeric t-PA/u-PA molecules
      including t-PA(AA1-263)/scu-PA(AA144-411), t-PA(AA1-274)/scu-PA(AA138-411) and t
      PA(AA87-274)/scu-PA(AA138-411). Conversion of single-chain to two-chain forms of
      u-PA or inhibition of active two-chain forms with plasminogen activator inhibitor
      1 or with the active site serine inhibitor phenyl-methyl-sulfonyl fluoride, did
      not alter the reactivity in the assay. In contrast, inactivation with alpha 2
      antiplasmin or with the active site histidine inhibitor Glu-Gly-Arg-CH2Cl
      resulted in a 3- to 5-fold reduction of the reactivity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377418
TI  - Alteration of adenine nucleotide metabolism in coronary smooth muscle cells by
      activated platelets.
AB  - Cultured porcine coronary smooth muscle cells were preloaded with [3H]adenine and
      the inside and outside radioactive metabolites of the cells were analyzed
      following exposure to activated platelets. Incubation of the cells with human
      platelets activated by collagen enhanced intracellular conversion of ATP to ADP
      and caused dose- and time-dependent increase in radioisotopic release, mainly
      adenosine. Isolation of cyclic AMP revealed decreased cyclic AMP levels in the
      treated cells, both intra- and extracellularly. Of the substances released by the
      activated platelets, thromboxane A2 and serotonin enhanced radioisotopic release.
      The modulation of adenine metabolism by the activated platelets was preceded by
      increase in accumulation of inositol phosphates in the cells and was prevented by
      Iloprost (1 microM), a prostacyclin analog, cilostamide (10 microM), a cyclic AMP
      specific phosphodiesterase inhibitor, or dibutyryl cyclic AMP (1 mM). Nifedipine
      showed only minor preventive effect. The agents which elevate cyclic AMP
      accumulation also attenuated phosphoinositide hydrolysis, whereas nifedipine had
      no effect. These results suggest that activated platelets may stimulate adenine
      metabolism in coronary smooth muscle cells, presumably due to activation of
      phosphoinositide turnover resulting in increased intracellular calcium. Enhanced
      adenosine release from the cells exposed to activated platelets may be a
      compensatory mechanism to prevent further platelet aggregation and contraction of
      coronary smooth muscle.

PMID- 1377419
TI  - Effect on primary haemostasis of prophylactic regimens of low molecular weight
      heparin, unfractionated heparin, dextran and their combinations. An animal
      experimental study.
AB  - The aim of the study was to determine whether an impairment of the haemostasis
      could be observed experimentally when thromboprophylactic substances, which act
      differently on the haemostatic mechanism, were given single or in combination in
      prophylactic doses. In 36 rabbits we measured the primary haemostatic plug
      formation time (PHT), rebleedings and total haemostatic plug formation time (THT)
      after transection of venules and arterioles using an intravital microscope. We
      combined unfractionated heparin (UH) and low molecular weight heparin (LMWH) in
      low dose with either dextran 70 or polygeline (placebo volume expander) in a
      randomized double-dummy set up. In the placebo group (NaCl and polygeline) the
      median PHT was 55 and 101 seconds for arterioles and venules respectively, which
      are well-comparable to earlier results from our group. Most prolonged PHT and THT
      for arterioles were seen for dextran+NaCl, actually less prolongation was seen
      for UH+dextran. We did not observe any differences, except for a prolongation of
      THT for venules in rabbits given dextran+NaCl (p less than 0.05). Thus, in
      thromboprophylactic doses used, there does not seem to be an impaired or additive
      effect between heparins and dextran 70 in primary haemostasis in rabbits.

PMID- 1377420
TI  - Somatotopy in the human supplementary motor area.

PMID- 1377422
TI  - Quantal analyses of quantal analysis.

PMID- 1377421
TI  - An essential 'set' of K+ channels conserved in flies, mice and humans.
AB  - The molecular genetic approach to studying K+ channels has revealed that at least
      four subfamilies of voltage-gated K+ channels originally discovered in Drosophila
      are conserved in mice and humans. This conservation of the K+ channel subfamilies
      Shaker, Shal, Shab, and Shaw suggests that not only the broad outlines of
      membrane electrical properties but also many molecular details as well evolved in
      the parent species ancestral to both invertebrate and vertebrate life. Shaker,
      Shal, Shab, and Shaw K+ channels have similar structures, but appear to be
      independent channel systems: when co-expressed in Xenopus oocytes, all four
      function independently. These four K+ channel subfamilies may be part of an
      essential 'set' of excitable channels required by most nervous systems. The task
      now remaining is to understand the functions of each member of the set.

PMID- 1377423
TI  - Target influences on the development of leech neurons.
AB  - A pair of Retzius neurons is found in each segmental midbody ganglion of the CNS
      of the leech Hirudo medicinalis. Although all Retzius neurons appear to have the
      same cell lineage and are indistinguishable from one another through the initial
      phases of axonogenesis, later in development two pairs of Retzius neurons--those
      in the segments containing the male and female reproductive ducts--acquire
      distinctive morphological and physiological characteristics. Experimental
      manipulations of the reproductive ducts in early embryos have indicated that the
      outgrowing Retzius axons receive a signal from these peripheral targets that
      triggers major changes in their developmental program. Such 'end-organ
      specification' has been shown to contribute to the differentiation of neurons in
      other nervous systems as well, and the mechanisms underlying such control can be
      investigated in great detail in the relatively simple, segmented nervous system
      of the leech.

PMID- 1377424
TI  - Control of eye-head coordination during orienting gaze shifts.
AB  - Combined eye and head displacements are routinely used to orient the visual axis
      rapidly (gaze). Humans can use a wide variety of head movement strategies.
      However, in the cat, comparatively limited eye motility forces a more routine and
      stereotyped use of head motion. Nevertheless, the same general principles of gaze
      control may be applicable to humans, rhesus monkeys and cats. The gaze control
      system can be modeled using a feedback system in which an internally created,
      instantaneous, gaze motor error signal--equivalent to the distance between the
      target and the gaze position at that time--is used to drive both eye and head
      motor circuits. The visual axis is moved until this error equals zero. Recent
      studies suggest that the superior colliculus of the cat provides brainstem eye
      and head motor circuits with the gaze motor error signal; such studies have led
      to speculation that information on ongoing gaze motion is fed back to the
      superior colliculus. It is still uncertain whether comparable collicular and
      brainstem neuronal mechanisms control gaze in the monkey.

PMID- 1377425
TI  - Getting the message from the gene to the synapse: sorting and intracellular
      transport of RNA in neurons.
AB  - A key question in cellular neurobiology is how neurons target molecules to
      cellular microdomains at a distance from the nucleus. Of special importance are
      the thousands of postsynaptic sites that form the basis for synaptic
      communication. Recent evidence suggests that an important aspect of molecular
      trafficking involves differential sorting, selective intracellular transport, and
      docking of particular mRNA molecules and associated protein synthetic machinery
      at postsynaptic sites. This offers the potential for local regulation of the
      production of key proteins in response to conditions at individual synapses. This
      article reviews what is known about the mechanisms of mRNA trafficking in neurons
      and in other cells ranging from oocytes to oligodendrocytes, and considers the
      possible role that mRNA trafficking and the resulting local synthesis of
      particular proteins may play in cellular function.

PMID- 1377426
TI  - Neural substrates of opiate withdrawal.
AB  - Drug withdrawal is an integral part of most types of dependence and, to a large
      extent, opiate withdrawal has been considered the prototypic, classic measure of
      opiate dependence. The opiate withdrawal syndrome is characterized by multiple
      behavioral and physiological signs such as behavioral activation, ptosis,
      diarrhea, 'wet dog' shakes and motivational dysfunction, which may be represented
      in the CNS at multiple sites. It seems that the activating effects associated
      with the opiate withdrawal syndrome may be mediated by the nucleus locus
      coeruleus. Other signs such as wet dog shakes may involve sites in the
      hypothalamus important for temperature regulation. Certain other signs such as
      diarrhea and lacrimation may be dependent on peripheral opiate receptors. The
      motivational aspects of opiate withdrawal as demonstrated by the aversive
      stimulus effects or negative reinforcing effects (e.g. disrupted lever-pressing
      for food and place aversions) may involve those elements of the nucleus accumbens
      that are known to be important for the acute reinforcing effects of opiates in
      nondependent rats. Evidence exists at the cellular and molecular level for both
      'within-system' and 'between-system' adaptations to dependence. Elucidation of
      the neural networks, cellular mechanisms and molecular elements involved in
      opiate withdrawal may provide not only a model for our understanding of the
      adaptive processes associated with drug dependence but also of those associated
      with other chronic insults to CNS function.

PMID- 1377427
TI  - [Mental diseases are not popular].

PMID- 1377429
TI  - [Epidemiology and natural course of benign prostatic hyperplasia].
AB  - Benign prostatic hyperplasia (BPH) is a frequent condition in men over 50 years
      of age. At autopsy the histological characteristics of BPH are seen in 80% of all
      men older than 80 years. Although BPH is so frequent, its precise etiology is
      still unknown. Each of the various sources from which epidemiological data on BPH
      can be obtained has its own specific problems in terms of potential errors and
      biases, which have to be taken into account in interpretation of the data from
      these sources. There are clear differences in the incidence of BPH in various
      races. In negroids BPH is more frequent than in Caucasians, while in Asiatic
      races BPH is less frequent. However, in Asiatics BPH occurs more frequently in
      men who have immigrated into western countries. Age and hormonal status are well
      known to be involved in the development of BPH. Other factors, such as marital
      status, socioeconomic class, smoking, diet, diabetes, hypertension, and liver cir
      rhosis have been implicated, but their relation with the risk of developing BPH
      has never been proven. The natural history of BPH is characterized by an age
      dependent increase in histological changes and an increase in prostate size. The
      histological changes compatible with BPH are found in men below the age of 30
      with an incidence of less than 10%. During the 6th decade, 42% of prostatic
      specimens have histological signs of BPH and during the 8th decade of life more
      than 80% of prostatic specimens. The histological changes of BPH precede
      prostatic enlargement by roughly 1 decade. There is an initial spurt of prostate
      growth during the period of maturation and puberty.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377430
TI  - [Clinical manifestations and indications for therapy of benign prostatic
      hyperplasia].
AB  - The high incidence of benign prostatic hyperplasia (BPH), together with the wide
      variability in its clinical manifestations and in the natural course of disease,
      requires a careful evaluation of the patient. Technical progress and continuing
      development of established methods mean that a wide range of diagnostic
      procedures is available and an "objective" correlate of infravesical obstruction
      can be obtained. In addition to these objective criteria, the patient's
      subjective perception of the impact of the symptoms on his quality of life also
      affects the decision as to whether therapeutic intervention should be attempted
      and the degree of success that can be attained, as is becoming increasingly
      evident. The diagnostic methods available for the routine assessment of patients
      with BPH is reviewed, and their relative value as a basis for deciding on
      therapeutic intervention is analysed.

PMID- 1377428
TI  - Immunohistochemical detection of acidic fibroblast growth factor in bladder
      transitional cell carcinoma.
AB  - Acidic fibroblast growth factor (aFGF) is a regulatory peptide which, on account
      of its structural homologies with the products of oncogenes, is involved in cell
      proliferation, differentiation, and motility. We previously reported the presence
      of aFGF in the urine of patients with transitional cell carcinoma (TCC). aFGF can
      also induce the motility of a rat-derived bladder carcinoma cell line (NBTII).
      This immunohistochemical study used polyclonal rabbit antibodies against acidic
      and basic FGF and peroxidase detection. Native NBTII nude mice xenografts and
      aFGF transfected NBTII (NFS14) nude mice xenografts were used as tissue controls
      for antibody specificity. The samples included 4 normal urothelia and 12 TCC. In
      addition, cytospins of 4 different tumoral cell lines of human bladder and normal
      bladder cells were stained. The results showed strong immunostaining in all
      tumoral urothelium samples using anti-aFGF and a very low amount of staining or
      none at all in healthy tissues. A primary analysis suggested that the strongest
      reaction was obtained in high-grade tumors (3 + vs + for lower-grade tumors).
      Using bFGF antibody, strong immunohistochemical staining was detected on basal
      membranes and stromal vessels and none in urothelium. These data confirm aFGF
      expression in the epithelial cell compartment of bladder cancer and the likely
      involvement of this regulatory peptide in the biology of TCC.

PMID- 1377431
TI  - [Value of functional examination techniques for the assessment of the clinical
      aspects of benign prostatic hyperplasia].
AB  - The urodynamic relevance of benign prostatic hyperplasia (BPH) is determined by
      evaluation of the symptoms of prostatism, the degree of infravesical obstruction
      and the size of adenoma. The combination of all three findings, but also the
      presence of at least of two of these findings suggest a diagnosis of clinical
      BPH. Standard diagnostic procedures consist in elicitation of the history,
      evaluation of symptoms, physical examination, urinalysis and laboratory
      examination of serum creatinine; with evaluation of residual urine and
      uroflowmetry in addition, surgical therapy can be expected to be successful in
      93%. Urinary flow rates exceeding 15 ml/s and/or discrepancies between symptoms
      and findings need further assessment by synchronous pressure-flow studies for
      differential diagnosis between unobstructed flow and high-flow outflow
      obstruction. Complete videourodynamic investigation is indicated both in patients
      with combined BPH and urinary incontinence without residual urine and in patients
      with BPH and suspected or known neurological disorder. Surgical treatment of BPH
      involves the risk of postoperative incontinence in patients with detrusor
      hyperreflexia combined with a functional or morphological lesion of the external
      urinary sphincter.

PMID- 1377433
TI  - [Benign prostatic hyperplasia and growth factors: mechanisms and hypotheses].
AB  - The aetiology and pathogenesis of benign prostate hyperplasia (BPH) are still
      unresolved questions, although a number of hypotheses have been developed, most
      of which have still not been confirmed by experimentation. BPH has been regarded
      as a kind of adenoma, as a stromal disease, as the result of either hormonal
      imbalance (altered oestrogen/testosterone ratio) or testosterone or
      dihydrotestosterone stimulation, and finally as the result of oestrogen
      stimulation, perinatally or involutionally. More recently, scientific interest
      has focused on the presence and possible function of growth factors and their
      receptors in the human prostate and their autocrine or paracrine stimulatory
      effects in BPH development. Hypotheses on their hormonal regulation as well as
      their interplay during epithelial-stromal interaction have been developed. The
      intact human prostate produces epithelial (EGF) and basic fibroblast (bFGF)
      growth factors. Normally, they do not appear to have autocrine or paracrine
      effects. In androgen deficiency, however, as shown experimentally in castrated
      rats, the stromal cells express increased amounts of TGF beta, of TGF beta
      receptor, and of bFGF. Platelet-derived growth factor (PDGF), but not the
      corresponding receptor, has been shown in prostate. The growth factor receptor
      associated tyrosine protein kinase is present in the human prostate in two
      different forms, but its functional significance in BPH development has not yet
      been elucidated. A more significant role may be attributed to the recently
      described growth factors in cultured human stromal cells, which exert
      multifarious mitogenic and non-mitogenic effects on prostatic epithelium as well
      as neuronal and non-neuronal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377432
TI  - [Evaluation of new technical alternative procedures for therapy of symptomatic
      benign prostatic hyperplasia].
AB  - Transurethral resection of the prostate is still the gold standard in the
      treatment of symptomatic benign prostatic hyperplasia. It has proved possible to
      reduce the mortality of this treatment almost to zero, while the morbidity has
      remained unchanged at 18% for decades. Therefore, understandably, procedures are
      being looked for that will be similarly effective but have lower morbidity.
      Current developments in this field are transurethral implants (spiral,
      intraurethral catheter, Wall-Stent), the balloon dilatation, transurethral
      incision (TUIP), laser therapy (TULIP, ITK), ultrasound-induced aspiration of
      tissue and heat treatment (hyperthermia, thermotherapy). Chances and risks
      inherent in these different technical procedures and the amount of investment
      they involve are reviewed. Potential for the future can at best be attributed to
      the Wall-Stent, TUIP, the application of laser and the thermotherapy.

PMID- 1377434
TI  - Nondetectable prostate-specific antigen in moderately differentiated
      adenocarcinoma of prostate.
AB  - Prostate-specific antigen (PSA) is a glycoprotein derived from prostatic ductal
      and acinar epithelial cells. The main clinical use of PSA is as a marker of
      prostate tumor progression/recurrence. We present a case of a sixty-nine-year-old
      patient with recurrent endometrioid carcinoma of the prostate (status post
      radical prostatectomy, hormonal therapy, and external beam radiation therapy)
      with normal serum PSA.

PMID- 1377435
TI  - Prostate-specific antigen and digital rectal examination in long-term follow-up
      of stage A1 prostatic carcinoma.
AB  - Twenty-six individuals with Stage A1 carcinoma of the prostate (less than or
      equal to 5%, Gleason score less than or equal to 4) diagnosed from 1969 to 1980
      were evaluated with digital rectal examination (DRE) and prostate-specific
      antigen (PSA). This unique cohort, sixty-one to eight-two years of age (median 72
      years), had a mean interval from diagnosis of thirteen years (median 12.5 years).
      Abnormal findings on DRE were found in 6 individuals, whereas only one elevated
      PSA was detected. Ninety-six percent of the PSA levels were less than 3.0 ng/mL
      and nearly 60 percent of the group had 1.0 ng/mL or less. These levels compare
      favorably with healthy control subjects under forty years of age and with the
      limited data available for PSA in healthy men over seventy years of age (87% and
      26%, respectively). While biopsy showed persistent or recurrent carcinoma in 2 of
      5 individuals, further evaluation disclosed only localized disease. Though the
      PSA provided little additional information to DRE in the individual patient, it
      appears from an overview of this group that a low level of PSA in Stage A1
      prostatic carcinoma may be associated with long-term survival.

PMID- 1377436
TI  - Enhanced chemiluminescent enzyme immunoassay for the detection of trichinellosis
      antibodies in pigs.
AB  - A modified enhanced chemiluminescent enzyme assay (ECIA) was developed for mass
      screening of pigs for trichinellosis antibodies in abattoirs. Using Bionectics
      beads as solid support, the assay time could be reduced to 45 min. Optimal
      conditions for washing, blocking, incubation, concentration of serum, antigens
      and conjugates as well as timing of film exposure were determined. The
      sensitivity and specificity of the assay were found to be comparable to those of
      the triple antibody-IgG ELISA. The assay was tested in an abattoir and its
      efficacy was found to be satisfactory. However, the major disadvantage of the
      assay is the high cost of magnetic beads.

PMID- 1377437
TI  - An improved passive hemagglutination test for the serological diagnosis of bovine
      fascioliasis using the specific antigen f2.
AB  - Optimum conditions for coupling the specific antigen f2 of Fasciola hepatica to
      sheep red cells and for the preparation of control cells coated with an unrelated
      protein are described. With a careful selection of donor sheep for erythrocytes,
      the problem of anti-species antibodies in bovine sera has been overcome and
      results may be obtained within 1 h as only one step is required in the assay
      system. Incorporation of a concentration of 25 mM CaCl2 in the diluent achieved
      increased stability of the agglutinates and enabled a more precise estimation of
      the end-point to be made. Analyses performed on bovine sera obtained at slaughter
      provided results in good agreement with the presence of flukes or fascioliasis
      lesions in livers at routine slaughter inspection. The developed assay is
      simpler, faster, more sensitive (P less than 0.01) and has a cut-off between
      populations of negative sera more easy to define than a recently marketed enzyme
      linked immunosorbent assay.

PMID- 1377438
TI  - In vitro properties and experimental pathogenic effect of three strains of feline
      immunodeficiency viruses (FIV) isolated from cats with terminal disease.
AB  - Three strains of virus isolated from peripheral blood mononuclear cells (PBMC) of
      sick cats were identified as feline immunodeficiency virus (FIV) on the basis of
      in vitro cytopathic effect, T-lymphotropism, ultrastructural morphology and
      magnesium-dependent reverse-transcriptase activity. The pathogenic properties of
      two isolates were studied in 13 experimentally infected cats. The primary phase
      of infection was characterised by a range of haematological (neutropenia,
      lymphopenia, presence of atypical lymphocytes) and clinical alterations (fever,
      various signs lasting several weeks, generalised lymphadenopathy persisting for
      several months) and specific seroconversion. A correlation between the inoculated
      dose of virus and the intensity and duration of clinical signs was observed. The
      primary phase was followed in the 10 surviving cats by a stage of asymptomatic
      seropositivity of undetermined duration but which has persisted for over 35
      months for the earliest infections. Viruses reisolated several weeks or months
      after experimental infection retained the same in vitro properties as the initial
      isolates.

PMID- 1377439
TI  - Metabolism by rat liver cytosol of illudin S, a toxic substance of Lampteromyces
      japonicus. II. Characterization of illudin S-metabolizing enzyme.
AB  - 1. Enzyme systems responsible for formation of cyclopropane ring-cleavage
      metabolites (M1 and M2) of illudin S in rat liver were characterized. 2. The
      enzymes were localized in the cytosol fraction and utilized NADPH alone as
      electron donor; they were not affected by oxygen and had low pH optima. 3.
      Formation of metabolites M1 and M2 was inhibited completely by dicumarol (10(-4)
      M), an inhibitor of DT-diaphorase. 4. Menadione (10(-4) M) and quercetin (10(-4)
      M) both inhibited formation of M1 and M2 by 35% and 15%, respectively, but
      quinacrine, barbital, pyrazole and p-chloromercuribenzoic acid had no significant
      effect. 5. Results show that the enzyme systems may differ from DT-diaphorase,
      aldehyde oxidase, xanthine oxidase, ketone reductase, aldose reductase, aldehyde
      reductase and alcohol dehydrogenase, known cytosolic enzymes responsible for
      xenobiotic metabolism.

PMID- 1377440
TI  - [N-glycosylation of proteins in rheumatic diseases].

PMID- 1377441
TI  - Stimulation of the summit of the right ventricular aspect of the ventricular
      septum during orthodromic atrioventricular reentrant tachycardia.
AB  - Application of ventricular premature complexes (VPCs) from the right ventricular
      (RV) apex during orthodromic atrioventricular (AV) reentrant tachycardia has
      limitations both in the ability to shorten the succeeding atrial cycle length and
      in helping to identify accessory pathway location. Stimulation from the summit of
      the RV aspect of the septum during AV reentrant tachycardia was investigated as a
      new technique to improve the diagnostic utility of applying VPCs during AV
      reentrant tachycardia. VPCs were induced during AV reentrant tachycardia at 10 ms
      decrements in patients with left free wall (n = 15), posteroseptal (n = 5), and
      right free wall (n = 3) accessory pathways from the RV apex and then from the
      summit of the RV septum. When the His was refractory, shortening of the atrial
      cycle length was noted in 13% of patients with left free wall pathways, in 60% of
      patients with posteroseptal pathways, and in 100% of patients with right free
      wall pathways with VPCs from the RV apex, and in 47, 100 and 100%, respectively,
      with VPCs from the summit of the septum. When all VPCs were considered, there was
      a significant shortening of the atrial cycle length in 67% of patients with left
      free wall pathways when stimulated from the RV apex, which increased to 93% with
      summit stimulation. An extrastimulus applied on or after the His effected a
      significant shortening of the atrial cycle length in no patients with left free
      wall pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377443
TI  - Ca(2+)-activated nonselective cation channel in apical membrane of vestibular
      dark cells.
AB  - Patch-clamp recordings were made on cell-attached and excised apical membrane
      from dark cells of the semicircular canal of the gerbil. These cells are thought
      to secrete K+ and absorb Na+ from the luminal fluid (endolymph). Single-channel
      events were identified as being equally conductive (27.6 +/- 0.4 pS; n = 48) for
      K+, Na+, Rb+, Li+, and Cs+ and 1.4 times more permeable to NH4+ but not permeable
      to Cl-, Ca2+, Ba2+, nor to N-methyl-D-glucamine. The channels displayed linear
      current-voltage relations that passed nearly through the origin (intercept: -2.6
      +/- 0.5 mV; n = 48) when conductive monovalent cations were present on both sides
      of the membrane in equal concentrations. Channel activity required the presence
      of Ca2+ at the cytosolic face; there was no activity at less than or equal to 10(
      7) M Ca2+ and full activity at greater than or equal to 10(-5) M Ca2+. Cell
      attached recordings had a mean reversal voltage of -36.4 +/- 7.9 mV (n = 7),
      which was interpreted to reflect the intracellular potential of dark cells under
      the present conditions. We have identified a nonselective cation channel in the
      apical membrane of vestibular dark cells that might participate in K+ secretion
      or Na+ absorption under stimulated conditions, but the density appears to be
      insufficient to fully account for the transepithelial K+ flux.

PMID- 1377442
TI  - Hepatitis C testing. Comparison of Ortho's EIA and RIBA II tests in 1,182
      patients undergoing primary liver transplantation.
AB  - Plasma samples from 1,182 patients undergoing primary liver transplantation were
      tested for anti-hepatitis C (HCV) virus by two methods: Ortho HCV ELISA Test
      System (EIA) and Chiron RIBA HCV Test System (RIBA II). The EIA results, 0 or +,
      were recorded first, followed by RIBA results, N = negative, P = positive, or I =
      indeterminate. Concordant results--0N, + P, + I--were found in 1,076 (91%), and
      discordant results were found in 106 (9%). The EIA optical density did not relate
      to concordant or discordant results. Band patterns were described by stating the
      band position (1, 2, 3, or 4) and inserting a dash (-) if no band was visualized.
      Most + P samples fell into two patterns: 47% showed all four bands, pattern 1234,
      and 15% showed the two-band pattern, 34. When the EIA was negative, 0P, the
      opposite was seen: 8% showed the 1234 pattern and 81% showed the 34 pattern.
      There were 226 samples that formed bands (+ P, 149; 0P, 31; + I, 15; 0I, 31). The
      frequency of bands was as follows: 4, 32%; 3, 31%; 2, 19%; and 1, 18%. Band 2 and
      the EIA test detected antibodies to the same c100-3 fragment and showed 74%
      concordance. No explanation is apparent for the lower concordance rate here than
      that between the EIA test and bands 3 = 96% or 4 = 88%. The EIA and RIBA II
      tests, together with positive liver function tests and abnormal tissue pathologic
      findings, provide a basis for the diagnosis of HCV.

PMID- 1377444
TI  - InsP3 and Ins(1,3,4,5)P4 act in synergy to stimulate influx of extracellular Ca2+
      in Xenopus oocytes.
AB  - To investigate the role of D-myo-inositol 1,3,4,5-tetrakisphosphate
      [Ins(1,3,4,5)P4] in the regulation of Ca2+ influx, we injected inositol
      phosphates into Xenopus oocytes and measured Ca(2+)-gated Cl- current to assay
      intracellular free Ca2+ concentration ([Ca2+]i). To assess Ca2+ influx, we
      removed extracellular Ca2+ or added the inorganic Ca2+ channel blocker Mn2+ to
      the extracellular bath and measured the resulting change in Cl- current.
      Ins(1,3,4,5)P4 did not cause Ca2+ influx when injected alone or when preceded by
      an injection of Ca2+. In contrast, Ins(1,3,4,5)P4 stimulated Ca2+ influx when
      injected after the poorly metabolized inositol trisphosphate (InsP3) analogues D
      myo-inositol 1,4,5-trisphosphorothioate [Ins(1,4,5)P3S3] or D-myo-inositol 2,4,5
      trisphosphate [Ins(2,4,5)P3]. These results indicate that Ins(1,3,4,5)P4 is not
      sufficient to stimulate Ca2+ influx but acts in synergy with InsP3s to cause Ca2+
      influx. We also studied the effect of Ca2+ influx on the immediate metabolism of
      D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] in single oocytes. Ca2+ influx
      shunted the metabolism of Ins(1,4,5)P3 toward the formation of Ins(1,3,4,5)P4 and
      away from D-myo-inositol 1,4-bisphosphate [Ins(1,4)P2]. These results suggest
      that there is a positive feedback regulatory mechanism in which Ca2+ influx
      stimulates Ins(1,3,4,5)P4 production and Ins(1,3,4,5)P4 stimulates further Ca2+
      influx.

PMID- 1377445
TI  - Blockers of platelet-derived growth factor-activated nonselective cation channel
      inhibit cell proliferation.
AB  - In serum-deprived G(o)-arrested cells, the addition of serum or growth factors
      initiates a cascade of events that culminates in DNA synthesis and mitosis.
      Recently, we showed that in mouse L-M(TK-) fibroblasts a 28-pS nonselective
      cation channel (NS channel) becomes quiescent at G(o) arrest and rapidly active
      within seconds of platelet-derived growth factor (PDGF) or serum addition,
      placing this response very early in the postreceptor signaling cascade. However,
      lack of specific channel blockers hindered determination of whether channel
      activation was necessary for mitogenesis. Derivatives of N-phenylanthranilic acid
      (DCA) have been reported to block a pancreatic nonselective channel. Therefore,
      using single-channel analysis, we examined the effect of these agents on the L
      M(TK-) NS channel. Flufenamic acid and mefenamic acid rapidly produced reversible
      channel block with an inhibitory constant (Ki) approximately 10 microM.
      Furthermore, the component of the macroscopic K+ efflux shown to be mediated by
      the NS channel was blocked with a similar Ki value. DCA effects on cell
      proliferation were tested by measuring cloning efficiency and growth rate. Both
      were inhibited over the range of concentration that affected channel activity,
      and a 50% inhibitory dose of 50-100 microM was determined. This observation
      further substantiates the hypothesis that NS channel activation forms a necessary
      component in the transduction of the mitogenic signal from the PDGF receptor.

PMID- 1377446
TI  - Gs and Gi protein subunits during cell differentiation in intestinal crypt-villus
      axis: regulation at the mRNA level.
AB  - The expression of subunits of the guanine nucleotide regulatory protein that
      mediates hormonal stimulation of adenylyl cyclase (Gs) and of the guanine
      nucleotide regulatory protein that mediates hormonal inhibition of adenylyl
      cyclase (Gi) was studied during cell migration and differentiation in the rat
      small intestine crypt-villus axis. Proliferative crypt cells were separated from
      nonproliferative mature villus cells and the following data were obtained: 1)
      alpha s subunits were more abundant in crypt cells than in villus cells as
      evidenced by cholera toxin-catalyzed [32P]NAD ribosylation and Western blotting
      of this relative molecular weight (M(r)) 42,000 protein; 2) alpha i2- and alpha
      i3-subunits (M(r) 40,000 and M(r) 41,000, respectively) were preferentially
      expressed in villus cells as evidenced by pertussis toxin-catalyzed [32P]NAD
      ribosylation and Western blotting (alpha i1-subunit was not detectable in
      intestinal epithelium by using these techniques); 3) Western blotting showed a
      higher expression of the common beta- (M(r) 36,000) subunit of G proteins in
      villus cells than in crypt cells; and 4) Northern blot analysis using an alpha s
      subunit oligonucleotide probe showed a 1.9-kb mRNA that was more abundant in
      crypt cells than in villus cells. In contrast, alpha i2- and alpha i3-mRNA
      species (2.3 and 3.5 kb, respectively), analyzed by using specific cDNA probes,
      were much more abundant in villus cells than in crypt cells. Finally, two beta
      subunit mRNA species of 3.3 and 1.8 kb were detectable in intestinal epithelial
      cells and were more abundant in villus cells than in crypt cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377447
TI  - Sepsis-induced changes in protein synthesis: differential effects on fast- and
      slow-twitch muscles.
AB  - Sepsis is associated with severe muscle wasting. Mechanisms responsible for
      sepsis-induced alterations in muscle protein metabolism were investigated in vivo
      and compared with changes induced by nonseptic inflammation. The rate of protein
      synthesis in mixed hindlimb muscles was not altered in inflammation but was
      inhibited 50% in sepsis. This inhibition did not result from a decreased RNA
      content. Instead, the translational efficiency was significantly reduced by 50%
      in skeletal muscle of septic animals compared with control. The effect of sepsis
      to lower the rate of protein synthesis was further examined using individual
      muscles containing different fiber types. Both the protein concentration and
      protein synthetic rate in fast-twitch muscles were reduced by sepsis, whereas
      neither of these parameters was affected in slow-twitch muscles or heart. The
      decreased translational efficiency did not result from a change in the rate of
      peptide-chain elongation. Instead, the sepsis-induced inhibition of protein
      synthesis resulted from a restraint in peptide-chain initiation because sepsis
      caused a 1.6-fold increase in free ribosomal subunits. Overall, sepsis, but not
      inflammation, caused an inhibition of protein synthesis primarily in muscles
      composed of fast-twitch fibers. The mechanism involved in the reduced rates of
      protein synthesis in muscles resulted from an inhibition of peptide-chain
      initiation, with no change in peptide-chain elongation.

PMID- 1377448
TI  - Regulation of alpha 1-beta 3-NA(+)-K(+)-ATPase isozyme during meiotic maturation
      of Xenopus laevis oocytes.
AB  - During progesterone-induced maturation of Xenopus oocytes, the transport and
      ouabain binding capacity of Na(+)-K(+)-ATPase at the plasma membrane is
      completely downregulated. To elucidate the mechanism and the physiological
      significance of this process, we have followed the fate of oocyte alpha-beta 3
      Na(+)-K(+)-ATPase complexes during meiotic maturation and early embryonic
      development. An immunocytochemical follow-up of the catalytic alpha-subunit,
      ouabain binding studies, cell surface iodination, and oocyte cell fractionation
      combined with immunochemical subunit detection provides evidence that following
      progesterone treatment Na(+)-K(+)-ATPase molecules are retrieved from the oocyte
      plasma membrane. The enzyme complexes are recovered in an active form in an
      intracellular compartment in both in vitro and in vivo matured eggs. Exogenous
      Xenopus alpha 1- and beta 1-complexes expressed in the oocyte from injected cRNAs
      are regulated by progesterone similar to endogenous Na(+)-K(+)-ATPase complexes.
      Finally, active Na(+)-K+ pumps internalized during oocyte maturation appear to be
      redistributed to plasma membrane fractions during blastula formation in Xenopus
      embryos. In conclusion, our data suggest that endocytosis of alpha 1- and beta 3
      complexes during meiotic maturation of Xenopus oocytes is responsible for
      downregulation of Na(+)-K(+)-ATPase activity and results in an intracellular pool
      of functional enzymes, which might be reexpressed during early development in
      response to physiological needs.

PMID- 1377449
TI  - Effect of osmotic swelling on K+ conductance in jejunal crypt epithelial cells.
AB  - To further elucidate differences in ion transport properties between jejunal
      crypt and villus cells, we compared the responses of purified cell suspensions to
      hypotonic stress using electronic cell sizing to evaluate volume changes and 86Rb
      and 36Cl efflux. After hypotonic swelling, villus enterocytes undergo a
      regulatory volume decrease (RVD) due to the loss of K+ and Cl- through volume
      activated conductances. After 0.6x isotonic challenge in Na(+)-free medium, crypt
      cells exhibited only partial RVD, with t1/2 congruent to 15 min. The addition of
      a cation ionophore, gramicidin (0.25 microM), to hypotonically swollen crypt
      cells caused an accelerated RVD, which was complete with t1/2 congruent to 5 min.
      Crypt epithelial cells showed no volume-activated 86Rb efflux, but villus
      enterocytes had an increased rate of 86Rb efflux after hypotonic dilution (P less
      than 0.001). Gramicidin added to hypotonically diluted crypt cells greatly
      increased the rate of 86Rb efflux compared with controls. Both villus (30 s; P
      less than 0.005) and crypt (2 min; P less than 0.001) cells exhibited volume
      activated 36Cl efflux in absence of gramicidin. Cl- channel blockers anthracene-9
      carboxylate (9-AC, 300 microM) and indanyloxyacetic acid (IAA-94, 100 microM)
      prevented crypt RVD (P less than 0.001) in the presence of gramicidin. Ouabain (P
      less than 0.001) or K(+)-free Na(+)-containing medium, but not Ba2+ (5 mM) or
      quinine (100 microM), prevented crypt partial RVD. We conclude that crypt cells
      lack volume-activated K+ conductance. The RVD exhibited by crypt cells, although
      partial, was due to Cl- loss through a volume-activated Cl- conductance and Na+
      loss via Na(+)-K(+)-ATPase.

PMID- 1377450
TI  - Anion channels in rat liver canalicular plasma membranes reconstituted into
      planar lipid bilayers.
AB  - Previous studies from this laboratory have demonstrated a Cl(-)-HCO3- exchanger
      and have provided evidence for a Cl- conductance in rat liver canalicular plasma
      membrane vesicles. To further investigate the apical Cl- conductance, we
      performed single-channel analysis after incorporation of canalicular liver plasma
      membrane vesicles into planar lipid bilayers. This was necessary, because the
      canalicular membrane is not accessible for the patch-clamp technique. Two types
      of anion channels could be identified (30- and 90-pS conductance) corresponding
      to the class of small and intermediate channels, respectively. The kinetics of
      the small channel were found to be voltage dependent with a maximum for the open
      probability at -20 mV. In contrast, intermediate channel kinetics were voltage
      independent. The anion channels described above could allow electrogenic Cl-
      efflux, to compensate Cl- influx via the electroneutral Cl(-)-HCO3- exchanger.
      Further studies will be required to prove their functional importance in bile
      formation.

PMID- 1377451
TI  - Dietary regulation of pancreatic amylase in transgenic mice mediated by a 126
      base pair DNA fragment.
AB  - Expression of the mouse pancreatic amylase gene Amy-2.2 is increased
      approximately 10-fold in response to increasing the carbohydrate content of the
      diet from 9.6 to 74%. The DNA sequence mediating this response has been localized
      to the 5' flanking region of the amylase gene by analysis of hybrid constructs in
      transgenic mice. The results define a 127-base pair dietary response unit that
      includes two previously described regulatory elements, an insulin-responsive
      element and a pancreatic enhancer. Fragments containing these two elements alone
      fail to respond to diet, demonstrating a requirement for additional regulatory
      sequences. Another mouse amylase gene Amy-2.1 is only minimally responsive to
      insulin and to diet. The data are consistent with the hypothesis that the insulin
      response element is necessary but not sufficient for regulation of amylase by
      dietary carbohydrate.

PMID- 1377452
TI  - Growth and developmental regulation of wnt-2 (irp) gene in mesenchymal cells of
      fetal lung.
AB  - The wnt gene family encodes a group of proteins implicated as intercellular
      signaling molecules in vertebrate development. Because many wnt genes are also
      expressed in the lung, we have examined whether the wnt family member wnt-2 (irp)
      plays a role in lung development. We have cloned rat wnt-2 and found that this
      cDNA detects multiple mRNAs expressed at high levels in fetal rat lung. Much
      lower levels were found in adult rat lung and other tissues, including,
      surprisingly, the mammary gland. The wnt-2 mRNA was also detected in human fetal
      lung fibroblast cell lines, where the mRNA levels were dramatically regulated by
      growth state as well as growth factor stimulation. In situ hybridization showed
      that, in fetal rat lung, wnt-2 mRNA expression is restricted to the mesenchyme;
      levels in the developing epithelium were indistinguishable from background. Based
      on the known properties of other wnt proteins, our data lead us to propose that
      wnt-2 may play a role in lung development by mediating intercellular
      interaction(s) between mesenchyme and epithelium.

PMID- 1377453
TI  - Monocrotaline pyrrole alters DNA, RNA and protein synthesis in pulmonary artery
      endothelial cells.
AB  - Administration of monocrotaline pyrrole (MCTP) to animals results in pulmonary
      vascular injury. Pulmonary vascular endothelium is a likely target for this
      pneumotoxicant. Cultured porcine pulmonary artery endothelial cells (PECs)
      treated with MCTP remain viable but are unable to divide and exhibit an altered
      morphology. Such responses raise a question about the extent to which affected
      cells carry out normal functions such as RNA and protein synthesis. Accordingly,
      the cellular activity of MCTP-treated PECs was examined in this study. PECs were
      treated with a single administration of MCTP or vehicle, and determinations of
      cell number, protein, and DNA content were made at times up to 7 days
      posttreatment. DNA, RNA, and protein synthesis were quantified by incorporation
      of [3H]thymidine, [3H]uridine, and [3H]leucine, respectively. Increases in cell
      number that occurred with time in the control cells were reduced in MCTP-treated
      cells. At 7 days posttreatment, both protein and DNA content increased above
      control levels. Synthesis of DNA, RNA, and protein continued in all treatment
      groups throughout the posttreatment period, but cells treated with high
      concentrations of MCTP showed less synthetic activity than controls during the
      initial 48 h posttreatment. By 7 days, MCTP-treated cells were producing
      significantly more DNA, RNA, and protein. These results indicate that cells
      treated with MCTP continue to synthesize DNA, resulting in an increased DNA
      content. In addition, treated cells continue to synthesize RNA and translate RNA
      into protein. Thus, cellular activity is maintained but altered substantially by
      MCTP exposure.

PMID- 1377454
TI  - Cloning and sequence analysis of rat cystic fibrosis transmembrane conductance
      regulator.
AB  - A complementary DNA (cDNA) encoding the rat cystic fibrosis transmembrane
      conductance regulator (CFTR) has been isolated and the tissue distribution of the
      rat CFTR mRNA has been determined. Northern blot analysis revealed that the
      highest levels of the 6.3 kilobase (kb) CFTR mRNA were expressed in the colon,
      with expression also noted in uterus, lung, stomach, and small intestine. A 7.5
      kb mRNA was expressed in skeletal muscle, and in testes both the 7.5-kb mRNA and
      a 6.0-kb mRNA were expressed. Five cDNAs were isolated from a rat colon library,
      the longest corresponding to codons 684 through the poly A tail. Three other
      clones, corresponding to codons 213 through 245, 372 through 574, and 656 through
      886 were also isolated. Polymerase chain reaction amplification of cDNA prepared
      from rat colon mRNA was utilized to clone the remainder of the cDNA. The
      predicted amino acid sequence of the rat CFTR is 79% identical to the human CFTR,
      with 73% identity noted in the R domain, and 81 and 83% identities noted in
      nucleotide binding folds 1 and 2, respectively. Thirty-two of the 38 potential
      phosphorylation sites identified in the human CFTR were also present in the rat
      CFTR.

PMID- 1377456
TI  - Enzymatically amplified time-resolved fluorescence immunoassay with terbium
      chelates.
AB  - We report an ultrasensitive, enzymatically amplified, time-resolved fluorescence
      immunoassay with a terbium chelate as the detectable moiety. In this immunoassay,
      the primary label is the enzyme alkaline phosphatase (ALP). ALP cleaves phosphate
      out of a fluorogenic substrate, 5-fluorosalicyl phosphate, to produce 5
      fluorosalicylic acid (FSA). 5-Fluorosalicylic acid can then form a highly
      fluorescent ternary complex of the form FSA-Tb(3+)-EDTA, which can be quantified
      by measuring the Tb3+ fluorescence in a time-resolved mode. In this assay,
      exceptional sensitivity is achieved because of the enzymatic amplification
      introduced by ALP and the quantification by laser-induced microsecond time
      resolved fluorometry. Time-resolved fluorometry is applicable because of the long
      fluorescence lifetime of the Tb3+ complexes. It is shown that in a model AFP
      assay 10(6) or 1.5 x 10(5) molecules can be detected (final assay volume, 100
      microL) by using monoclonal or polyclonal detection antibodies, respectively. The
      assay demonstrates excellent precision (approximately 4%), and it seems to be
      highly suited for automated, sensitive, and rapid immunoassays.

PMID- 1377455
TI  - [Histamine release during induction of combination anesthesia using nalbuphine or
      fentanyl. Modulation of the reaction by premedication with
      promethazine/pethidine].
AB  - In a controlled clinical trial in patients admitted for general surgery (mainly
      abdominal and thyroid), histamine release following nalbuphine 1 mg/kg i.v.
      versus fentanyl 5 micrograms/kg i.v. was studied in the course of an otherwise
      routine induction with promethazine/pethidine as premedication 30 min before the
      opioids and alcuronium-flunitrazepam-thiopental 5 min later. Succinylcholine was
      given before intubation and further analgesia was obtained by repeated
      administration of either nalbuphine or fentanyl. Plasma histamine levels were
      measured by a specific fluorometric assay, heart rate and blood pressure were
      measured for assessing hemodynamics, and clinical signs of anaphylactoid
      reactions such as skin eruptions and arrhythmias were registered. RESULTS.
      Nalbuphine and fentanyl both released histamine with an incidence of more than
      40%. In addition, nalbuphine potentiated the histamine release evoked by the
      sequential administration of alcuronium-flunitrazepam-thiopental in one complex
      of application. The incidence of histamine release in the nalbuphine group was
      6/13 = 46%, in the fentanyl group only 1/11 = 9% (chi2 test, P less than 0.05).
      Furthermore, this study showed high histamine levels after succinylcholine and
      intubation in a relation to time of administration that suggested histamine
      release as a stress response to intubation. Finally, the incidence of histamine
      release after a second injection of the opioids was still 30%. A direct
      correlation between plasma histamine levels, hemodynamic changes, and skin
      reactions could not be shown. A detailed causality analysis with histamine
      release as a contributory determinant showed histamine release less detrimental
      to hemodynamic stability than the opposite, which had been expected. However, the
      promethazine administered 30 min before induction of anaesthesia had strong H1-
      and H2-receptor antagonistic activity and was given with optimum timing for H1-
      and H2-prophylaxis. CONCLUSION. The study demonstrated that histamine release
      during anaesthesia and surgery depends strongly on the time sequence of drugs and
      measures used. Histamine release is not predictable from studies in human
      volunteers alone; studies in patients have to be added. Histamine release is not
      always detrimental. H3-receptor-mediated effects after H1- and H2-prophylaxis may
      help patients to counteract the effects of a series of vasoactive drugs given
      during induction of anaesthesia.

PMID- 1377457
TI  - Influence of hydroxyethyl starch on coagulation in patients during the
      perioperative period.
AB  - The perioperative use of hydroxyethyl starch (HES) has been implicated as a
      possible cause of intracranial bleeding. The purpose of this study was to compare
      the influence on blood coagulation of the isovolemic replacement of 1-L blood
      loss with either 6% HES (molecular weight [MW] average: 450,000) or 5% human
      albumin during neurosurgery or lower abdominal surgery. Twenty patients scheduled
      for brain tumor surgery and 20 patients undergoing transabdominal hysterectomy
      were studied. The activated partial thromboplastin time, prothrombin time,
      fibrinogen concentration, factor VIII coagulant, von Willebrand factor antigen,
      platelet count, and the activated clotting time were compared after induction of
      anesthesia, after administration of 500 and 1000 mL of colloid solution, and 24
      and 48 h postoperatively. All measured coagulation variables remained within
      physiologic range. Changes in coagulation indices were identical in neurosurgical
      and hysterectomy patients, except for a larger increase in fibrinogen
      concentration 24 and 48 h after hysterectomy. The acute phase reaction of factor
      VIII coagulant and von Willebrand factor, which plays a role in postoperative
      hypercoagulability, was attenuated by the use of HES. We conclude that isovolemic
      replacement of 1-L blood loss with either 6% HES (MW average: 450,000) or 5%
      human albumin does not interfere with normal hemostasis during and after
      neurosurgery or lower abdominal surgery.

PMID- 1377458
TI  - Halothane relaxes preconstricted small and medium isolated porcine coronary
      artery segments more than isoflurane.
AB  - To compare the putative vasodilatory effects of isoflurane versus halothane on
      porcine coronary arteries, we studied the capacity of isoflurane and halothane to
      relax K(+)-constricted (30 mM) small (0.5-1.0 mm outside diameter [OD]) and
      medium (1.0-1.5 mm OD) porcine coronary arteries with use of in vitro tension
      recording. We also examined the effect of the dihydropyridine calcium channel
      agonist BAY K8644 on previously constricted epicardial porcine coronary artery
      segments in the presence of halothane or isoflurane. Our purpose was to determine
      (a) whether anesthetic effect on coronary arteries varied with arterial diameter,
      and (b) whether halothane and isoflurane inhibited BAY K8644-induced contraction
      of coronary vessels. Small and medium porcine coronary artery segments were
      constricted with K+ (30 mM) and the resulting contraction was allowed to
      stabilize. This was followed by exposure to 0.5%, 1.0%, 2.0%, and 3.0% isoflurane
      or halothane and the resultant tension was again measured. Potassium-induced
      contractions were significantly relaxed by halothane in small coronary artery
      segments at 0.5%, 1.0%, 2.0%, and 3.0% and in medium coronary artery segments at
      1.0%, 2.0%, and 3.0%. Potassium-induced contractions were significantly reduced
      by isoflurane only at 3.0% in both small and medium coronary artery segments.
      Halothane caused significantly more relaxation of both small and medium porcine
      coronary arteries previously constricted with K+ (30 mM) than did isoflurane.
      There were no significant differences in coronary artery response to isoflurane
      or halothane with respect to coronary artery diameter. These experiments indicate
      that in porcine coronary arteries greater than 0.5 mm OD, studied in vitro after
      K(+)-induced contraction, isoflurane was not a potent coronary
      vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377459
TI  - Treatment of gastric lymphoma.
AB  - A review of 52 patients with gastric lymphoma at the Texas A&M University College
      of Medicine Affiliated Scott and White Memorial Hospital (Temple, TX). was
      performed to determine the influence of different treatment modalities. Thirty
      one patients had a potentially curative resection, while 21 underwent a
      palliative procedure or biopsy alone. Overall 5-year survival was 73.4 per cent
      after curative resection and 38.3 per cent for lesser operative procedures (P
      less than .005). Adjuvant radiation was given to 14 patients after curative
      resection with a 5-year survival rate of 71.5 per cent compared to 82.4 per cent
      in the 17 patients treated by curative resection alone (nonsignificant). Patients
      who underwent palliative surgery or biopsy who received postoperative radiation
      therapy had a 38.0 per cent 5-year survival rate compared to a 0.0 per cent 5
      year survival rate in patients who received no therapy (P = .18). The authors
      conclude that curative resection is the treatment of choice for gastric lymphoma,
      but radiation therapy may offer some benefit when complete resection is not
      feasible.

PMID- 1377460
TI  - Tracheo-esophageal fistula complicating carcinoma of the esophagus.
AB  - In a 35-year review of 557 patients with esophageal carcinoma, 26 tracheal
      esophageal fistulas were encountered. Seventeen arose among patients with
      advanced disease or poor performance status and these patients were given comfort
      measures only. Treatment was attempted in 9 patients, 4 of whom died peri
      operatively. The remaining 5 avoided early pulmonary deaths. In principle,
      esophageal exclusion and bypass should provide the best palliation in patients
      whose performance status permits it, but extensive surgical procedures are futile
      in patients with established pulmonary sepsis. For most patients, not candidates
      for exclusion procedures, endoprostheses are more appropriate.

PMID- 1377461
TI  - Effect of interleukin-3 on responsiveness to granulocyte-colony-stimulating
      factor in severe aplastic anemia.

PMID- 1377462
TI  - [Staging evaluation and surveillance in tumors of the testicle].
AB  - In 1992, the staging and follow-up of testicular germ cell tumours is based on a
      combination of computed tomography and tumour markers. Due to the development of
      medical imaging over the last decade, abdominal and thoracic CT has now replaced
      the combination of lymphography and pulmonary tomographies. Testicular
      ultrasonography is valuable for the diagnosis and contributes to staging and
      follow-up. The chest x-ray is still performed and MRI has very exceptional
      indications. Tumour markers, essentially alpha-foetoprotein and the free beta
      fraction of human chorionic gonadotrophin, are useful in more than 80% of NSGCTs
      and about 15% of seminomas (beta-HCG alone). A very high initial level often
      indicates a poor prognosis. Monitoring of markers is essential after exclusive
      orchidectomy and to assess the efficacy of chemotherapy.

PMID- 1377463
TI  - Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid
      arthritis.
AB  - Antibodies to the stratum corneum of rat oesophagus (antikeratin antibodies) were
      assayed by indirect immunofluorescence in a prospective study of patients with
      early rheumatoid arthritis (RA). At the beginning of the study, antikeratin
      antibodies of IgG class were detected in serum samples from 27/71 (38%) patients
      compared with 1/20 (5%) control patients with reactive arthritis, and 1/38 (3%)
      healthy blood donors. At the end of the two year follow up, 27/67 (40%) patients
      with RA were positive for antikeratin antibodies. The patients with RA who were
      initially positive for antikeratin antibodies had a more active disease course
      than the patients negative for antikeratin antibodies as measured by clinical,
      laboratory, and radiological variables. The prevalence of positivity for
      antikeratin antibodies fluctuated during the follow up, the variation paralleling
      the disease activity. The occurrence of HLA-DR4 was similar in patients with RA
      who were positive and negative for antikeratin antibodies. Antikeratin antibodies
      were also found in seronegative patients with RA, confirming that antikeratin
      antibodies do not have rheumatoid factor activity. These results show that
      antikeratin antibodies are detectable at the time of the initial diagnosis of RA
      and that the positivity for antikeratin antibodies may have prognostic
      significance in early RA.

PMID- 1377464
TI  - Neurotensin augments intestinal regeneration after small bowel resection in rats.
AB  - Massive small bowel resection (SBR) is characterized by increased proliferation
      of residual gut mucosa and pancreas. Neurotensin (NT), a gut tridecapeptide,
      stimulates growth of normal gut mucosa and pancreas. This study examined whether
      NT affected growth of the small intestine and the pancreas after either distal or
      proximal SBR. Male Fischer 344 rats were divided into four groups. Group 1
      underwent ileal transection with reanastomosis (SHAM) and group 2 underwent 70%
      distal SBR. Group 3 underwent SHAM operation (jejunal transection), and group 4
      underwent 70% proximal SBR. After operation, each group was further subdivided to
      receive either saline (control) or NT (300 micrograms/kg) subcutaneously in
      gelatin every 8 hours for 7 days. At death, the pancreas and proximal jejunum
      (from groups 1 and 2) or distal ileum (from groups 3 and 4) were removed,
      weighed, and analyzed for DNA, RNA, and protein content. Both proximal and distal
      SBR significantly increased mucosal growth in the remnant intestine; a more
      pronounced effect was noted with proximal SBR. Administration of NT significantly
      augmented the adaptive changes in both groups of rats by mechanisms involving
      increases in both cell size (hypertrophy) and cell number (hyperplasia).
      Pancreatic growth was stimulated by distal (but not proximal) SBR; NT did not
      augment this response. The authors conclude that NT augments intestinal growth
      after SBR by mechanisms involving an increase in overall mucosal cellularity.
      Administration of NT may be therapeutically useful to enhance mucosal
      regeneration during the early period of adaptive hyperplasia after SBR.

PMID- 1377466
TI  - Extracellular collagenous spherules in salivary gland tumors. Immunohistochemical
      analysis of laminin and various types of collagen.
AB  - Collagenous spherulosis is a benign breast lesion involving lobular acini and
      ductules and containing eosinophilic spherules measuring up to 100 microns in
      diameter. We present an immunohistochemical analysis of similar collagen-rich
      spherules that are also found in salivary gland tumors. These collagenous
      spherules contain varying amounts of acidic mucins, elastin, basement membrane
      proteins including type IV collagen and laminin, and considerable amounts of
      interstitial collagen types I and III. Types II and VI collagen were not detected
      in collagenous spherules of salivary gland tumors. The cells surrounding these
      collagenous spherules expressed muscle actin, S100 protein, vimentin, and
      cytokeratins 8, 18, and 19, indicating that these cells have myoepithelial
      characteristics.

PMID- 1377465
TI  - [Meningiomas: immunohistochemical analysis of 26 cases].
AB  - We have analyzed, with immunohistochemical staining techniques 26 meningiomas of
      CNS. Vimentin intermediate filaments was present in all cases in the cytoplasm of
      tumoral cells. Single epithelium cytokeratin was positive in only 19% cases, same
      that was obtained with S-100 protein. Whereas 69% of cases expressed epithelial
      membrane antigen. No case was stained positively with Actin, Desmin and GFAP. The
      results obtained for others authors are analyzed.

PMID- 1377467
TI  - Developments in the control of testicular function.
AB  - Clinicians and clinical investigators have developed improved means for
      controlling testicular function in men. New and refined approaches for
      stimulation and inhibition of the hypothalamic-pituitary-testicular axis are now
      available. This chapter reviewed the most successful ways to inhibit the
      reproductive axis in men and its current application to the treatment of
      precocious puberty, metastatic prostate cancer, benign prostate hyperplasia and
      as prospective male contraceptives. Safe, effective and reversible medical
      approaches to male contraception are now approaching reality. Azoospermia and
      severe oligozoo/azoospermia can now be accomplished in the majority of men with
      combined GnRH antagonists and replacement doses of testosterone. Androgens and
      androgen-progestogen concentrations will induce azoospermia in over 90% of Asian
      men and azoospermia or severe oligospermia in Caucasian ethnic groups. Field
      trials are ongoing to determine whether testosterone administration will be more
      effective than condoms as contraceptives. True precocious puberty can now be
      managed more effectively than in the past by suppression of gonadotropin
      secretion with GnRH analogues. Precocious puberty due to other causes can be
      treated more effectively with inhibitors of steroidogenesis and blockers of
      androgen action. Metastatic prostate cancer, previously treatable with either
      castration or oestrogens, is now amenable to suppression of androgen secretion.
      GnRH analogues are given either alone or combined with blockers of androgen
      action. While significant palliative effects are observed with endocrine ablative
      therapy in most men with Stage C or D prostate cancer, modest increases in
      duration of survival may be seen. Benign prostate hyperplasia was previously
      approachable only with surgical intervention. Recent data have suggested that
      medical treatment with 5 alpha-reductase inhibitors and/or selective alpha
      adrenergic blockers may offer non-surgical alternatives in some patients. More
      data are needed to determine the role of medical management of this common
      disorder.

PMID- 1377468
TI  - Apparent specificity of bovine seminal ribonucleases can depend on the conditions
      used for the isolation of substrate.
AB  - RNAase SPL, a ribonuclease isolated earlier from bovine seminal plasma, was shown
      to possess the ability to produce large acid-insoluble fragments of Mg(2+)
      containing RNA in a limit digest. The factor which could be responsible for this
      apparent specificity has been identified as polyvinyl sulphate; it has been shown
      that polyvinyl sulphate inhibits RNAase SPL at much lower concentrations than
      required for RNAase A. The earlier results are now reinterpreted based on this
      effect of polyvinyl sulphate, thus providing a plausible explanation for RNAase
      SPL's apparent specificity. RNAase SPL has been shown to be a mixture of two
      ribonucleases, RNAase SPL I and RNAase SPL II. RNAase SPL I is like RNAase A in
      its activity while RNAase SPL II, the major ribonuclease in seminal plasma,
      appears to be identical to RNAase BS1.

PMID- 1377469
TI  - Mammalian fetuin-binding proteins sarcolectin, aprotinin and calcyclin display
      differences in their apparent carbohydrate specificity.
AB  - The interferon antagonist sarcolectin, the protease inhibitor aprotinin and
      calcyclin whose expression is regulated by growth stimulation in quiescent
      fibroblasts display sialic acid-dependent binding to fetuin, visualized by solid
      phase assays using biotinylated fetuin. The potential functional importance of
      this property prompted its comparative characterization with an array of neutral
      or negatively charged sugars, sulfated polysaccharides and sialoglycoproteins as
      inhibitors of binding of biotinylated fetuin to the immobilized proteins. The
      results revealed that this activity of sarcolectin and calcyclin is nearly
      unaffected by charge-free carbohydrates in contrast to aprotinin, calcyclin
      exhibits a notable affinity for Neu5Gc and together with aprotinin for
      phosphorylated sugars, and that sarcolectin's binding is affected to the highest
      extent by sulfated sugars relative to aprotinin and calcyclin.

PMID- 1377471
TI  - Conformational variations of the cis-syn cyclobutane-type photodimer in DNA and
      RNA.
AB  - The recent NMR study of a cis-syn photodimer B-DNA 10mer-duplex (Taylor et al.,
      Biochemistry 29, 8858 (1990)) showed the cyclobutane (CB) ring with a puckered
      twist in a right-handed sense (CB+). This is opposite to that of the crystal
      structure of cis-syn d-TpT(cyano-ethyl)(d-T[p]T-CE) which has a left-handed
      puckered-twist (CB-)(Hruska et al., Biopolymers 25, 1399 (1986)). 2D-NOESY
      experiments were performed on cis-syn d-T[p]T and cis-syn U[p]U at 25 and 35
      degrees C, respectively, to investigate the puckering mode of the cyclobutane
      ring of isolated cis-syn photodimers of the DNA and RNA types. The DNA
      photodimers showed interconversion of the puckered-twist of the cyclobutane ring
      between CB- and CB+ and interconversion of the glycosidic angle between syn and
      anti in both nucleoside residues. Interestingly, in the RNA photodimer only the
      CB- puckering mode with syn conformation of the glycosidic angle of the U[p]- was
      observed. These different dynamical behaviors of the photodimer in DNA and RNA
      might portend differential conformational effects on their corresponding normal
      nucleic acid regions. In addition these results indicate differences in the
      cyclobutane ring conformation of the cis-syn d-T[p]T, not only in solution and
      crystalline states, but also when the dimer is isolated and in duplex forms.

PMID- 1377470
TI  - Characterization of "modified-self"-induced specific antibody hyporesponsiveness
      to herpes simplex virus.
AB  - Pretreatment of mice iv with syngeneic spleen cells modified with soluble HSV
      envelope antigens induced an anti-HSV antibody hyporesponsiveness following
      challenge with infectious virus. The epitope density on the HSV-modified spleen
      cells was quantitated using a photon-counting spectrofluorimeter so that observed
      immunological results could be correlated with the HSV antigen dose on the
      splenocytes. The degree of anti-HSV antibody hyporesponsiveness was found to be
      related to the epitope density on the HSV-modified spleen cells, but not the
      number of modified cells used in the pretreatment over the 16-fold range tested.
      Anti-HSV antibody hyporesponsiveness was induced if 7, but not 3, days had
      elapsed between pretreatment and challenge. This antibody hyporesponsiveness
      could be adoptively transferred with T cells. Only mice that had induced an anti
      HSV antibody hyporesponsiveness following pretreatment with HSV-modified
      splenocytes were able to survive an LD50 challenge with infectious virus.

PMID- 1377472
TI  - Analysis of an RNA pseudoknot structure by CD spectroscopy.
AB  - The RNA PK5 (GCGAUUUCUGACCGCUUUUUUGUCAG) forms a pseudoknotted structure at low
      temperatures and a hairpin containing an A.C opposition at higher temperatures
      (J. Mol. Biol. 214, 455-470 (1990)). CD and absorption spectra of PK5 were
      measured at several temperatures. A basis set of spectra were fit to the spectra
      of PK5 using a method that can provide estimates of the numbers of A.U, G.C, and
      G.U base pairs as well as the number of each of 11 nearest-neighbor base pairs in
      an RNA (Biopolymers 31, 373-384 (1991)). The fits were close, indicating that PK5
      retained the A conformation in the pseudoknot structure and that the fitting
      technique is not hindered by pseudoknots or A.C oppositions. The results from the
      analysis were consistent with the pseudoknotted structure at low temperatures and
      with the hairpin structure at higher temperatures. We concluded that the method
      of spectral analysis should be useful for determining the secondary structures of
      other RNAs containing pseudoknots and A.C oppositions.

PMID- 1377473
TI  - Decreased expression of the membrane inhibitor of complement-mediated cytolysis
      CD59 on T-lymphocytes of HIV-infected patients.
AB  - OBJECTIVE: To study the expression of the membrane inhibitor of complement
      mediated cytolysis, CD59, on peripheral blood mononuclear cells (PBMC) from HIV
      infected individuals. METHODS: CD59 membrane expression was investigated by
      double immunofluorescent staining on purified PBMC from HIV-infected patients and
      seronegative controls. RESULTS: CD59 expression was decreased on peripheral blood
      T-lymphocytes from HIV-infected patients. Decreased expression of CD59 antigen
      did not correlate with clinical stage of disease. Low CD59 expression on T
      lymphocytes was mediated by several mechanisms, including: (1) decrease in number
      of CD4+ cells which normally express high amounts of the antigen; (2) relative
      increase in CD8+ cells, more specifically in CD8+ CD57+ cells expressing a low
      density of the antigen; (3) loss of or decreased CD59 expression on a
      subpopulation of CD3+ belonging either to the CD4+ or to the CD8+ subset.
      Decreased CD59 expression was consistently observed on CD8+ lymphocytes. CD59
      expression was normal on patient red blood cells, monocytes and B-lymphocytes.
      CONCLUSIONS: HIV infection is associated with a T-cell-specific defect in CD59
      membrane expression. Decreased CD59 expression may result in increased
      susceptibility of T-lymphocytes from HIV-infected patients to complement-mediated
      lysis.

PMID- 1377474
TI  - Cytolytic T-cell activity against mycobacterial antigens in HIV.
AB  - OBJECTIVES: The declining incidence of tuberculosis (TB) in developed countries
      has recently been reversed with the advent of HIV disease. This study proposes to
      document in vitro T-cell responses to mycobacterial antigens in HIV-infected
      individuals. DESIGN: T-cell-mediated immunity is recognized as one of the
      mechanisms of defence against TB. The cellular immunodeficiency and the
      importance of TB in the context of HIV disease has prompted use of in vitro
      assays of lymphocyte proliferation and cytolytic activity. METHODS: Peripheral
      blood mononuclear cells isolated from 29 HIV-infected patients (four with recent
      TB) and 11 healthy volunteers were stimulated with purified protein derivative
      (PPD). The responding blasts were presented to autologous antigen-primed
      macrophages to measure specific cytolytic T-lymphocyte (CTL) activity in vitro.
      RESULTS: T-cell proliferative responses were significantly lower in late stages
      of HIV disease. The degree of specific CTL activity was higher in healthy
      individuals than in Centers for Disease Control (CDC) stage II-III (P = 0.037),
      and CDC stage IV patients (P = 0.029). CONCLUSIONS: The clinical presentation of
      TB tends to be typical in early stages of HIV disease and atypical in late
      stages. The manifestations reflect the degree of immunodepression. This study
      documents the declining proliferative and cytolytic T-cell-mediated responses in
      HIV patients with progression of immunodeficiency.

PMID- 1377475
TI  - Ganciclovir with recombinant methionyl human granulocyte colony-stimulating
      factor for treatment of cytomegalovirus disease in AIDS patients.

PMID- 1377476
TI  - Single-step purification on DEAE-sephacel of recombinant polypeptides produced in
      Escherichia coli.
AB  - We describe a method for the purification of recombinant proteins based upon the
      selective interaction of the choline-binding domain of the pneumococcal murein
      hydrolase and tertiary amines. Proteins of interest, fused to the binding domain
      by a peptide linker, containing the cleaving sequence recognized by blood
      coagulation factor Xa, can either be assayed for biological activities in vitro
      and in vivo or have the binding moiety removed to yield a totally unmodified
      form, suitable for clinical and functional studies. The method can also be
      applied to the production of low molecular mass peptides. The principle of the
      technique is illustrated with acidic fibroblast growth factor and with a
      neuropeptide-like fragment of ten amino acids contained within its sequence.

PMID- 1377477
TI  - Analysis of NGF receptor gene products: generation of artifactual splice variants
      by PCR.

PMID- 1377478
TI  - Simple, inexpensive preparation of T1/T2 ribonuclease suitable for use in RNase
      protection experiments.

PMID- 1377479
TI  - Determination of coexisting nuclear transcription rates and cytoplasmic mRNA
      levels for gonadotropin subunit genes in rat anterior pituitary.
AB  - Nuclear run-on transcription assays allow the study of those factors that
      regulate the expression of a given gene. Because previously published protocols
      may have been presented in abbreviated form or not developed for nuclei derived
      from specific tissues, we have established a comprehensive protocol for those who
      wish to measure transcription of the gonadotropin subunit genes (alpha, LH-beta,
      FSH-beta) in the anterior pituitary of the rat. The protocol also allows the
      determination of simultaneously existing cytoplasmic subunit mRNA levels within
      the same cells. An especially critical step in nuclear run-on transcription
      assays is the isolation of newly formed labeled mRNA transcripts from the DNA
      template. In previously published protocols such isolation has been accomplished
      through rather tedious, multistep methods. To simplify this isolation process, we
      have evaluated the use of the commercially available product RNAzol. Nascent mRNA
      transcripts are attached to chromatin and the DNA template; proteinase K and
      DNase I are typically utilized to disrupt this attachment, thereby facilitating
      subsequent extraction. We have found that strict adherence to proteinase K and
      DNase I digestion prior to RNA extraction with RNAzol, followed by two
      ethanol/NH4OAc precipitations, will enable one to successfully isolate nascent
      mRNA transcripts free of unincorporated nucleotides. In summary, we present a
      comprehensive protocol for determining transcription rates and cytoplasmic mRNA
      levels for the gonadotropin subunit genes in the anterior pituitary of the rat.
      RNAzol was found to simplify the extraction of newly formed transcripts and
      should prove applicable with transcription assays utilizing nuclei from a variety
      of tissue.

PMID- 1377480
TI  - [The palliative treatment of pancreatic cancer: percutaneous drainage versus
      surgical diversion].
AB  - In a retrospective study, the outcome of 56 patients with unresectable carcinoma
      of the exocrine pancreas undergoing two palliative operations (bypass surgery vs
      percutaneous transhepatic biliary drainage with endoprosthesis) for the
      management of biliary obstruction was evaluated. Morbidity and mortality were
      similar in the two groups. Postop hospital stay was 8 days for the intubated, and
      15 days for operated patients (p less than 0.01). Although the symptom-free
      period was similar in both groups, intubated patients had a shorter period of
      poor-quality life.

PMID- 1377481
TI  - [Spontaneous rupture of the spleen in a patient hypercoagulated with dicumarol].

PMID- 1377482
TI  - The effect of sodium butyrate on the growth characteristics of human cervix
      tumour cells.
AB  - Sodium butyrate has been shown to affect cell proliferation, and, at
      concentrations above approximately 0.5 mM, to cause cell death in some tumour
      cell lines. When combined with cytotoxic drugs increase in chemosensitivity has
      been observed. We are presently carrying out a study of the combined effects of
      sodium butyrate and cytotoxic drugs on cultured cervix tumour cells. To provide a
      baseline for this study we have carried out a systematic investigation of the
      effects of sodium butyrate alone on the growth characteristics of cervix tumour
      cells cultured as multicell spheroids. This has shown that concentrations of n
      butyrate of 0.005 mM to 0.50 mM decrease cell proliferation without inducing cell
      death, the effect increasing with increasing concentration. Butyrate
      concentrations greater than 0.50 mM cause cell death after a period of 5 to 15
      days exposure, dependent on concentration. Concentrations of 0.010 mM and above
      cause fragmentation of, and increased cell shedding from, multicell spheroids,
      suggesting an effect on the cell surface. Concentrations of butyrate greater than
      0.10 mM cause a considerable increase in the synthesis of cytokeratin, as shown
      by reaction with cytokeratin antibody. Correlated with this is a marked increase
      in cell size, concentrations of butyrate of 2.0 or 3.0 mM leading to an
      approximate doubling of cell diameter, followed by cell disintegration. The
      effects of butyrate less than 0.25 mM are readily reversible. At concentrations
      greater than 0.25 mM the effects are reversible up to a limit of about 7 to 20
      days depending on concentration, even when cytokeratin synthesis has been
      induced.

PMID- 1377484
TI  - A Medical Research Council (MRC) randomised trial of palliative radiotherapy with
      two fractions or a single fraction in patients with inoperable non-small-cell
      lung cancer (NSCLC) and poor performance status. Medical Research Council Lung
      Cancer Working Party.
AB  - Two policies of palliative thoracic radiotherapy for NSCLC have been compared in
      a randomised multicentre controlled trial aimed at simplifying the palliative
      treatment of patients with poor performance status. A total of 235 patients were
      entered. They had inoperable, microscopically confirmed disease, too advanced for
      'curative' radiotherapy. Their main symptoms were related to the primary
      intrathoracic tumour even if metastases were present, and they had a poor
      performance status. Patients were allocated at random to regimens of either 17 Gy
      given in two fractions of 8.5 Gy 1 week apart (F2 regimen, 117 patients), or a
      single fraction of 10 Gy (F1 regimen, 118 patients). Two patients (one in each
      group) were excluded from all analyses because they were found to have had
      previously treated malignant disease and had been admitted in error. On
      admission, 95% of the 233 eligible patients had cough, 47% haemoptysis, 59% chest
      pain, 64% anorexia, and 16% dysphagia. As assessed by the clinicians, these
      symptoms were palliated in high proportions of patients, ranging in the F2 group
      from 48% for cough to 75% for haemoptysis, and in the F1 group from 55% for
      anorexia to 72% for haemoptysis and chest pain. For all five symptoms the median
      duration of palliation was 50% or more of survival. All these results were
      similar in the two treatment groups. In contrast, on daily assessment by the
      patients using a diary card, those treated with the F2 regimen experienced
      substantially more dysphagia, which was recorded in 56% of the patients compared
      with 23% in the F1 group (difference 33%: 95% confidence interval 17-48%). The
      median survival from randomisation was 100 days in the F2 group and 122 days in
      the F1 group. The F1 regimen, as it requires only a single attendance for
      treatment, is recommended as a palliative regimen for patients with inoperable
      NSCLC and a poor performance status.

PMID- 1377483
TI  - Selective enhancement of the tumour necrotic activity of TNF alpha with
      monoclonal antibody.
AB  - The binding and biological activity of human TNF alpha on endothelial and tumour
      cells has been studied in the presence of monoclonal antibodies (MAbs). In
      particular, one monoclonal antibody to TNF alpha (MAb 32) has been identified
      which failed to inhibit binding and cytotoxicity of TNF alpha on WEHI-164 tumour
      cells but which was a potent inhibitor of TNF alpha-induced endothelial cell
      procoagulant activity on bovine aortic endothelial cells. The ability of MAb 32
      to inhibit selectively the actions of TNF alpha on endothelial cells but not on
      tumour cells suggests a mechanism for enhancement of the anti-tumour action of
      TNF alpha in vivo when in complex with this antibody. Treatment of tumour bearing
      mice (WEHI-164 and Meth A fibrosarcoma) with TNF alpha-MAb 32 complex resulted in
      a 5- to 10-fold enhancement in the potency of the cytokine in comparison to free
      TNF alpha. Complexes between this cytokine and other MAbs generally resulted in
      either no effect or inhibition of TNF alpha activity in vivo and in vitro.
      Neither intact MAb 32 nor FAb' fragments of MAb 32 showed any tumour regressive
      activity in the absence of TNF alpha. The FAb' fragments were equipotent to the
      bivalent form of the antibody in enhancing TNF alpha activity. These data provide
      evidence that it is possible to segregate the individual biological activities of
      TNF alpha with concomitant enhancement of the tumour regressive activity of the
      cytokine in vivo.

PMID- 1377485
TI  - Advanced breast cancer and its prevention by screening.
AB  - In discussions on breast cancer screening, much attention has been focussed on
      the possible morbidity generated by screening. Favourable effects like the
      prevention of advanced disease seem underestimated, probably because
      quantification is that difficult. To analyse the amount of care and treatment
      given to women with advanced breast cancer, we report on patients followed from
      first recurrence until death using patient files and national sources. A random
      sample of 60 female cases from computerised registries of two cancer centres and
      a sample of 20 cases from a non-computerised hospital registry was taken. A total
      of 68 patient files were sufficiently documented. A woman with advanced breast
      cancer is estimated to have a 39% loss in utility compared to a healthy woman
      (range 27-45%). Hormonal treatment is the main modality during 14 and
      chemotherapy during 4 months. Total medical cost from diagnosis of advanced
      disease until death amounts to 17,100 US dollars, or 21,000 when including
      extramural cost. The effect of breast cancer screening by preventing the
      occurrence of advanced disease is quantified. The resulting gain in quality of
      life contributes 70% of the total gain in quality of life. In the long run,
      almost half of the annual cost of screening will be offset by savings in the cost
      for advanced disease. Only the changes in palliative surgery and/or radiotherapy
      will be small in contrast to primary treatment changes. Besides the mortality
      reduction, screening is justified by the improvements in quality of life and cost
      savings for women prevented from reaching advanced disease.

PMID- 1377486
TI  - Monoclonal antipeptide antibodies to the glucocorticoid receptor.
AB  - The generation of monoclonal antibodies to synthetic peptides of the
      glucocorticoid receptor is described. Two antibodies to sequences from the DNA
      binding region are IgMs. Two other antibodies to sequences in the steroid binding
      region and the C-terminus belong to the IgG class. The specificity of the IgG
      binding to the receptor in an ELISA assay is demonstrated by competition with the
      relevant peptides. Both IgGs are able to recognize the receptor in Western blots,
      but do not form stable complexes in sucrose gradients. Steroid binding to the
      receptor is not influenced by preincubation with antibodies. This indicates that
      denaturation or distortion of the receptor is necessary for the accessibility of
      these antibodies to their epitopes. Both antibodies can be used to stain the
      glucocorticoid receptor in neoplastic cells of patients suffering from chronic
      lymphatic leukemia.

PMID- 1377487
TI  - Management of stage II Hodgkin's disease: 15 years experience at St.
      Bartholomew's Hospital.
AB  - One hundred seventy-seven consecutive patients with newly diagnosed stage II
      Hodgkin's disease (HD) (supradragmatic 157; infra diaphragmatic 20) were treated
      at St. Bartholomew's Hospital on the basis of pathologic stage (PS) in 84 (IIA
      69; IIB 15) and clinical stage (CS) in 93 (IIA 33, IIB 60) between January 1968
      and December 1984. The median follow up is 13 years. Overall, complete remission
      (CR) was achieved in 143 patients (75%) of whom 53 have had a recurrence. One
      hundred twenty-seven patients remain alive, the cumulative predicted survival at
      15 yrs being 70%. Mantle radiotherapy was prescribed to 88 patients with
      supradiaphragmatic HD, of whom 75 entered CR and 9 achieved good partial
      remission (GPR) (95%). The duration of remission correlated strongly with ESR
      (greater than 50 mm/h) and mediastinal thoracic ratio (less than 33% vs. greater
      than 33%) in a multivariate analysis (p = 0.05 and 0.02, respectively). 46/88
      patients remain in continuous first remission, the median duration of remission
      having not reached at 15 years. Combined modality therapy or chemotherapy alone
      was prescribed to 69 patients with supradiaphragmatic HD, CR being achieved in 51
      patients and GPR in 8 at the completion of all therapy. 48/59 patients continue
      in first remission. The duration of remission of patients receiving combined
      modality therapy or CT alone was significantly longer (p = 0.002) than that of
      patients receiving RT alone, in spite of the fact that the former group comprised
      predominantly of patients with unfavourable features.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377488
TI  - 5-Aza-2'-deoxycytidine (NSC 127716) in non-seminomatous testicular cancer. Phase
      II from the EORTC Early Clinical Trials Cooperative Group and Genito-Urinary
      Group.

PMID- 1377489
TI  - Kinetic immunodominance: functionally competing antibodies against exposed and
      cryptic epitopes of Escherichia coli beta-galactosidase are produced in time
      sequence.
AB  - The murine antibody response to Escherichia coli beta-galactosidase (GZ) was
      analyzed in vivo and in vitro by focusing on two families of antibodies that
      exert distinct conformational/functional activity on the antigen. Activating
      antibodies--defined by their capacity to increase the enzymatic activity of
      defective GZ produced by mutant strains of E. coli--are detected early after
      secondary challenge. Inhibiting antibodies, which interfere with antibody
      mediated enzyme activation, appear later and cause the abrupt fall of activating
      titer, a scenario suggesting either idiotype/anti-idiotype interaction or
      opposite pulsions exerted on the antigen molecule. Supporting the latter
      mechanism, the confrontation of mAbs of the two families produced classical
      competitive inhibition curves when the readout was enzyme activation, although
      they recognize two different epitopes of the same molecule: the activating mAb a
      quaternary conformation-dependent site of wild-type GZ, the inhibiting mAb a
      sequential determinant exposed only in denatured or in defective enzyme. The
      different timing of generation of these antibodies during the response may depend
      on a processing step necessary for unfolding of native antigen and consequent
      display of certain cryptic epitopes before they can trigger specific B cells. A
      picture emerges where the response to the various epitopes of a complex antigen
      is sequentially connected and where the uptake by antigen-presenting cells of
      antigen complexed with antibodies specific for the exposed epitopes may favor
      revelation of the cryptic ones.

PMID- 1377490
TI  - Transfection of HLA-DR-expressing DAP.3 cells with a cDNA clone encoding the
      glycosyl phosphatidylinositol-linked form of lymphocyte function associated
      antigen-3: biochemical features and functional consequences.
AB  - Structural and functional aspects of the accessory molecule lymphocyte function
      associated antigen (LFA)-3 (CD58) have been examined following the transfection
      of DAP.3 and P815 cells with a cDNA clone encoding the glycosyl
      phosphatidylinositol (GPI)-linked form of human LFA-3. Despite earlier
      observations that DAP.3 cells are deficient in GPI anchoring LFA-3 was expressed
      efficiently on DAP.3, as well as on P815 cells. Immunoprecipitation of LFA-3 from
      35S-labelled cells revealed that the molecule expressed on the DAP.3 cells had a
      molecular weight intermediate between the transmembrane and GPI-linked forms
      expressed by human B cells. This suggests that the DAP.3 cells have a default
      pathway whereby the RNA transcript which encodes the GPI-linked form of the
      molecule can also encode an integral membrane protein. Functionally, expression
      of LFA-3 by DAP.3 which had previously been transfected with the genes encoding
      HLA-DR1 led to a marked augmentation of the proliferative response of five out of
      eight anti-DR1 human T cell clones. This effect was not reproduced when DR1 and
      LFA-3 were expressed by separate populations of DAP.3 cells, suggesting that the
      ligands for CD2 and for the T cell's receptor must be expressed on the same cell
      membrane. Expression of human LFA-3 also led to a substantial increase in the
      proliferative response of human peripheral blood T cells to a DR alloantigen.
      Separation of T cells into CD45RO+ and CD45RO- populations revealed that the
      augmentation was more marked for the memory than the virgin population. The
      mechanisms responsible for these differences are discussed.

PMID- 1377491
TI  - Binding of substance P to monolayers and vesicles made of phosphatidylcholine
      and/or phosphatidylserine.
AB  - Analyses of interactions between substance P (SP) and phospholipids were
      performed by combined surface pressure and surface potential measurements in
      monolayers and by 13C-NMR experiments on liposomes. This study was carried out
      using synthetic SP molecules: [1-13C-Gly9]SP and [1-13C-Gly2]SP. Injection of SP
      into the aqueous subphase led to an expansion of phosphatidylcholine (PtdCho) or
      phosphatidylserine (PtdSer) monolayer surface area. An apparent association
      constant of SP for PtdSer was estimated to be around 10(6)-10(-7) M-1. The
      surface potential delta V/n varied linearly with the molecular area whereas the
      variation of surface pressure was biphasic, suggesting that at least two binding
      states contributed to the monolayer expansion. These two states Si (SP is
      inserted into the bilayer) and Ss (SP is stuck on the surface) were observed on
      vesicular membranes by 13C-NMR. The kinetic of interconversion between these two
      states can be estimated by NMR, the Ss state being the stablest one. No
      perpendicular insertion of SP into these vesicular preparations seemed to occur,
      as previously postulated. However, SP might form aggregates in contact with these
      model systems, leading to a loss of permeability of the lipid vesicles.

PMID- 1377492
TI  - Ion channel formation by duramycin.
AB  - The formation of ion channels by the nonadecapeptide antibiotic duramycin was
      examined using black lipid membranes and using the patch-clamp technique. In
      black lipid membranes made from glyceryl monooleate or a
      phosphatidylcholine/phosphatidylethanolamine mixture, duramycin induced complex
      fluctuations in membrane conductance, some step-like and some which were
      incapable of being resolved into discrete conductance states. Both conductance
      and largest step size increased with time. A similar time-dependent increase in
      conductance was seen in patch-clamp experiments with HCA-7 Colony 29 human
      colonic epithelial cell. The channels displayed weak anion selectivity and the
      smaller channels formed in patches from epithelial cells showed weak inward
      rectification. Channel formation by duramycin was achieved at lower
      concentrations when the black lipid membrane was made with phospholipid rather
      than with glyceryl monooleate. Lower concentrations were effective in generating
      conductances in epithelial cells than in bilayers. It is concluded that duramycin
      forms ion channels in both artificial and biological membranes. Accumulation of
      duramycin and coalescence of initially small channels into larger ones is
      considered to be responsible for the recorded behaviour and to final disruption
      of membranes.

PMID- 1377493
TI  - Inhibition of gramicidin channel activity by local anesthetics.
AB  - Ondrias et al. ((1986) Stud. Biophys. 115, 17-22) found that dibucaine,
      butacaine, and tetracaine reduce the conductance of membranes containing multiple
      (greater than 10(6)) gramicidin channels. Similar experiments with local
      anesthetics (LA's) added to the bath while gently stirring showed that the
      inhibition developed slowly over a time course of 5-10 min. We developed a many
      (10-20) channel membrane technique which demonstrated that when LA's were added
      to the bath and the membrane was repeatedly broken and reformed, the channel
      occurrence frequency declined promptly. In standard single-channel membrane
      experiments at lower gramicidin densities, the mean single channel conductance
      and lifetime distributions with LA's present in the bath did not differ from the
      controls. The predominant channel conductance amplitude was lower by 9.1% than
      those of controls, but channel amplitude distributions were also modified so that
      the net reduction in overall population channel conductance was only about 2.0%.
      Channel currents showed no evidence of flicker blocks. The lifetime histograms of
      control and LA-exposed channel populations were both satisfactorily fit by a
      single-exponential function with the same mean. Thus, inhibition is due primarily
      to a reduction in the frequency of occurrence of conducting channels, implying a
      reduced concentration of active monomers in the membrane.

PMID- 1377494
TI  - Studies of the influence of different cross-linking reagents on the immune
      response against a B-epitope.
AB  - We have previously shown that the carrier polytuftsin obtained by
      polycondensation of tuftsin, a naturally occurring macrophage activator,
      increases significantly the antibody response against a linked B-epitope. In the
      present work, we have studied the influence of different cross-linking reagents
      on the quality of the conjugation and on the immune response, at both B-cell and
      T-cell levels. We observed that the cross-linking method used for coupling the B
      epitope to the carrier influences the immune response. A hypothesis is put
      forward to explain the differences observed.

PMID- 1377495
TI  - Improved microscopic detection of bacteriuria.
AB  - A simple method is described which permits the microscopic detection of bacteria
      in sediments of urine and other fluids, including bacteria that have eluded
      detection by conventional means. The method introduces increased centrifugal
      force and stepwise chemical fixation and then conventional staining. It is rapid,
      economical, and suitable for use in a physician's office. Use of this method
      immediately reveals those bacteria reported as "significant" by the conventional
      laboratory culture. More importantly, living or dead, which are missed by the
      conventional culture and by the conventional Gram staining procedure. These
      bacteria usually can be grown in special media and they appear to be related to
      systemic disease as evidenced by the clinical response to appropriate
      antibiotics.

PMID- 1377496
TI  - Permanent stained preparations of synovial fluid for detection of calcium
      compounds using alizarin red S.
AB  - Permanent preparations of air dried synovial fluids were prepared by staining
      calcium compounds with alizarin red S stain; each slide was coverslipped with
      Permount. Variables studied were: (a) concentration of the solution of alizarin
      red S, (b) pH of staining solution, (c) time of incubation in staining solution
      and aqueous and ethanolic content of staining solution. The staining effect of
      each solution was tested on calcium pyrophosphate dihydrate, calcium oxalate,
      apatite and monosodium urate (MSU). Of all the solutions, best results were
      obtained with 0.25% alizarin red S in 50% ethanol at pH 7.0 for 30 min. With this
      solution, the calcium-containing compounds were well stained. MSU did not stain
      and still preserved negative birefringence on polarization. Fixation of smears
      with ethanol served a double purpose: It fixed the slides without dissolving or
      removing MSU or the calcium compounds, yet it did dissolve five corticosteroids
      commonly used for intra-articular injection which may interfere with
      interpretation of compensated polarized light microscopy of synovial fluids.

PMID- 1377497
TI  - Basic blue 54: a new colorant for monocytes.
AB  - C.I. basic blue 54, a sulfur containing azo textile dye, stained the nucleus and
      cytoplasm of normal and leukemic monocytes bright red-violet. Essential for the
      staining reaction was a brief final rinse in a pH 3.6 acetic acid-sodium acetate
      buffer. Coloration of the type found in monocytes was not observed in other types
      of mature and immature leukocytes.

PMID- 1377498
TI  - A simple staining procedure for detecting the true acrosome reaction in buffalo
      (Bubalus bubalis) spermatozoa.
AB  - A simple dual staining procedure for detecting the true acrosome reaction in
      dried smears of buffalo spermatozoa is described. Trypan blue is used first to
      differentiate live from dead spermatozoa and the dried smears which have been
      prepared are stained with Giemsa for acrosome evaluation. Four categories of
      spermatozoa were recognized: A) live, intact acrosome (acrosome pink, postnuclear
      cap clear); B) dead, intact acrosome (acrosome pink, postnuclear cap blue); C)
      live, detached acrosome (acrosome clear, postnuclear cap clear); and D) dead,
      detached acrosome (acrosome clear, postnuclear cap blue). The procedure is
      simple, rapid and convenient for assessing true acrosome reaction in buffalo
      spermatozoa. Simultaneous assessment of sperm viability and its acrosomal status
      in dried smears makes this procedure attractive because the true acrosome
      reaction can be studied thoroughly at a later state after the incubation period.

PMID- 1377499
TI  - Microwave enhanced staining for plant virus inclusions.
AB  - Plant virus inclusion bodies can be stained specifically with established
      staining methods for light microscopy. The procedure can be augmented by a short
      microwave treatment to provide better staining intensity and reduced staining
      time. The method is useful for preliminary sampling prior to collection for
      electron microscopy and for plant pathologists, plant breeders, and
      diagnosticians as a rapid means of plant virus characterization.

PMID- 1377500
TI  - A technique for embedding undecalcified bone samples for detecting alpha-emitters
      using vacuum impregnation with Spurr's resin.
AB  - A method has been developed by which large samples of mineralized bone,
      containing an alpha-emitter, can be embedded in Spurr's resin in a fraction of
      the time required by conventional methods. Bone samples were freeze-dried or
      fixed and dried prior to impregnation with Spurr's resin under vacuum. Sections
      were cut for the preparation of either alpha-track or fission-track
      autoradiographs using the solid state detector CR-39. This method is applicable
      to samples containing a mobile form of a radionuclide that may be translocated
      during the processes of fixation and dehydration of the specimen.

PMID- 1377501
TI  - New uses for calcium chloride solution as a mounting medium.
AB  - Fresh cross sections of stems (Psilotum nudum, Coleus blumei, and Pelargonium
      peltatum) and roots (Setcreasea purpurea) 120 microns thick were fixed in FPA50
      (formalin: propionic acid: 50% ethanol, 5:5:90, v/v) for 24 hr and stored in 70%
      ethanol. The sections were transferred to water and then to 1% phloroglucin in
      20% calcium chloride solution plus either hydrochloric, nitric, or lactic acid in
      the following ratios of phloroglucin-CaCl2 solution:acid: 25:4, 20:2, or 15:5.
      The sections were mounted on slides either in one of the three mixtures or in
      fresh 20% calcium chloride solution. A rapid reaction of the acid-phloroglucin
      with lignin produced a deep red color in tracheary elements and an orange-red
      color in sclerenchyma. Fixed and stored leaf pieces from Nymphaea odorata were
      autoclaved in lactic acid, washed in two changes of 95% ethanol, transferred to
      water, and treated with the three acid-phloroglucin-calcium chloride mixtures.
      The abundant astrosclereids stained an orange-red color similar to that of
      sclerenchyma in the sections. In addition, a new method is reported for
      specifically staining lignified tissues. When sections or leaf pieces are stained
      in aqueous 0.05% toluidine blue O, then placed in 20% calcium chloride solution,
      all tissues destain except those with lignified or partially lignified cell
      walls. Thus, toluidine blue O applied as described becomes a reliable specific
      test for lignin comparable to the acid-phloroglucin test.

PMID- 1377502
TI  - Viability and acrosome staining of bull, boar and rabbit spermatozoa.
AB  - A practical and reliable staining procedure was developed to distinguish the
      viability and acrosomal status of bull, boar and rabbit spermatozoa. The first
      stain with trypan blue or Congo red is rapid and avoids artifacts. This stain is
      precipitated by neutral red during the 2 min required for fixation. The
      precipitate gives a high contrast black color, resistant to the subsequent
      rinsing and persists during the time required for staining the acrosome with
      Giemsa. Ten classes of spermatozoa are distinguished (live or dead with intact
      acrosomes, loose acrosomes, damaged acrosomes, no acrosome, or with no acrosome
      and no postacrosomal ring). The intact acrosomes are purple, the loose acrosomes
      are dark lavender and the damaged acrosomes are pale lavender. The anterior part
      of the head of live spermatozoa with no acrosome is white or light pink and the
      same area of dead spermatozoa is white or pale gray. The postacrosomal ring is
      red. The postacrosomal area of the head of live spermatozoa is white or light
      pink and the same part of dead spermatozoa is black, dark violet or gray. The
      procedure did not give satisfactory results for stallion spermatozoa.

PMID- 1377503
TI  - Quantitative determination of murine dermal elastic fibers by color image
      analysis: comparison of three staining methods.
AB  - We compared three different staining methods to determine if the dermal elastic
      fiber content of the HRS/Skh-1 hairless mouse could be accurately measured by
      color image analysis. Comparisons were made among Kligman's modification of
      Luna's mast cell stain for elastin, Unna's orcein stain with or without potassium
      permanganate preoxidation, and Gomori's aldehyde fuchsin stain with potassium
      permanganate preoxidation. The color image analysis system could be used to
      identify and quantify murine dermal elastin fibers in sections stained by all
      three methods. Gomori's aldehyde fuchsin stain with preoxidation demonstrated
      twice the content of dermal elastic fibers demonstrated by either Kligman's
      modification of Luna's mast cell stain or Unna's orcein stain with or without
      preoxidation. Gomori's aldehyde fuchsin method with preoxidation should be
      considered the stain of choice for evaluating murine dermal elastic fiber
      content.

PMID- 1377504
TI  - Visualization of histamine binding to nuclei.
AB  - The binding of histamine to cultured microvascular endothelial cells and glycol
      methacrylate embedded ovarian tissue sections has been localized using
      fluorescein-albumin-histamine conjugate. Histamine conjugate was bound to the
      plasma membranes and nuclei of luteal, endothelial, and ovarian stromal cells. An
      apparent increase in the binding of histamine to nuclei was observed in the
      presence of cimetidine but the plasma membrane staining was still evident. Unlike
      cimetidine, pyrilamine completely inhibited the binding of histamine to the
      plasma membrane. Instead, in the presence of pyrilamine, histamine bound
      exclusively to the nuclei of endothelial, germinal epithelial, granulosa, and
      stromal cells. However, the nuclei of terminally differentiated luteal cells and
      oocytes were not labeled. The functional significance of these nuclear histamine
      binding sites remains to be determined.

PMID- 1377505
TI  - Improved intracellular morphology of Pneumocystis carinii from rat lung by
      postfixation with a mixture of potassium ferrocyanide and osmium tetroxide.
AB  - Pneumocystis carinii infected rat lungs were postfixed with a mixture of OsO4 and
      K4Fe(CN)6. A marked improvement in staining of cell membranes, endoplasmic
      reticulum, nuclear membranes and glycogen was observed. These improvements were
      seen in both the trophic and cystic forms of the organisms. The addition of
      K4Fe(CN)6 did not improve the staining of cell walls, microtubules or ribosomes.
      Trophozoites were seen attached to both type 1 and type 2 pneumocytes by
      filopodia and/or intercalation of the cell body of P. carinii with the host lung
      cells. It is expected that the improvement in ultrastructural detail will allow
      better understanding of the ultrastructure of P. carinii and provide insights
      into the modes of action of various antimicrobial compounds on this organism.

PMID- 1377506
TI  - A plastic embedding technique for analyzing fluorescent dextran-amine labelled
      neuronal profiles.
AB  - A plastic embedding technique employing fluorescently labelled dextran-amines is
      described. After application of tracer to cut nerves and appropriate transport
      time, animals were fixed in paraformaldehyde. Subsequently their brains were
      dissected, heads and brains were dehydrated, embedded in methacrylate and
      sectioned serially on a rotary microtome. Plastic sections allow high resolution
      of single neuron profiles and complete serial reconstruction of undistorted
      sections, including embryos with large amounts of yolk. In conjunction with whole
      mount analysis and double labelling, this technique can accurately reveal the
      spatial relationships of nerve components throughout development.

PMID- 1377507
TI  - Identification of basic nuclear proteins by their boronate complex.
AB  - A new histochemical reaction for the identification of histone type basic
      proteins has been developed. Carbonyldiimidazol is used to activate the basic
      proteins of TCA-extracted nuclei, their m-aminophenylboronic acid complex is
      prepared, and the DNA-free, histone-containing nuclei are stained with toluidine
      blue at pH 5.5.

PMID- 1377509
TI  - Effects of prostanoids on the rat's myometrium in vitro during pregnancy.
AB  - The objectives of this study were to determine the effects of pregnancy in the
      rat on the contractile response of the myometrium in vitro to a number of
      prostanoids. Longitudinally and circularly oriented strips were studied
      separately. Responses to PG (prostaglandin)F2 alpha, PDG2, the PGI2-mimetic
      iloprost, and the thromboxane (Tx) A2-mimetic U-46619 were investigated on Days
      10, 15, 18, 20, 21, and 22 of pregnancy. Responses were prostanoid-dependent, and
      differences between longitudinal and circular strips were small. PGF2 alpha and
      PGD2 produced similar patterns, with a high potency but low maximal response on
      Day 10; thereafter potency fell to a minimum value on Day 18 and then gradually
      increased until Day 22, when it was still lower than at Day 10. In contrast, for
      PGE2 there were no changes in potency over the period of study (longitudinal
      muscle) or a slight increase between Days 15 and 21 (circular muscle). Both
      iloprost and U-46619 maintained a low potency throughout pregnancy. We conclude
      that the pregnant rat's myometrium is probably not a target for PGI2 or TxA2 and
      that the difference patterns of responses to PGE2 and PGF2 alpha during pregnancy
      support the hypotheses that these prostanoids act at different sites within the
      myometrium.

PMID- 1377508
TI  - Embedding and fixation techniques for immunohistochemical staining with anti-DNA
      polymerase alpha and Ki-67 monoclonal antibodies to analyze the proliferative
      potential of tumors.
AB  - Anti-DNA polymerase alpha and Ki-67 are monoclonal antibodies that recognize
      nuclear antigens expressed in proliferating cells. In this study, we evaluated
      various methods of embedding and fixing brain tumor specimens to optimize
      staining with these antibodies. In fresh frozen sections, postfixation with 4%
      paraformaldehyde, 100% methanol, 95% ethanol and 10% buffered formalin were
      tested; also tested were prefixation with 4% paraformaldehyde followed by
      freezing and fixation with 100% methanol, 95% ethanol, or 10% buffered formalin
      followed by embedding in paraffin. For both antibodies, postfixation of fresh
      frozen sections with 4% paraformaldehyde at 4 C gave the most intense staining
      and lowest background activity while preserving histological features. This
      technique can be used in routine clinical practice to predict the growth
      potential of tumors.

PMID- 1377510
TI  - Voltage-gated calcium channels in rat Sertoli cells.
AB  - We have studied Ca2+ voltage-gated channels of immature rat Sertoli cells by
      measuring intracellular Ca2+ concentration and its variation following
      administration of various agents in fura-2-loaded, confluent monolayers in
      culture. Our findings indicate that the basal Ca2+ intracellular level is about
      100 nM, a value that falls within the range found in most eukaryotic cells. The
      intracellular Ca2+ level is rapidly increased by fetal bovine serum through
      release of intracellularly stored Ca2+ and opening of membrane cation channels.
      Substantial Ca2+ influx in rat Sertoli cells seems to be mediated by voltage
      gated cation channels, which are sensitive to nifedipine, nicardipine, and omega
      conotoxin. To investigate whether FSH, which controls several morphological and
      biochemical events of prepubertal Sertoli cells, modified Ca2+ influx in this
      cell type, we analyzed the cell response to acute FSH administration. The results
      show that, although not influencing the basal concentration of Ca2+, FSH
      decreases intracellular calcium influx induced by membrane depolarization.
      Similar data were also obtained by adding dibutyryl cAMP to the external medium
      and by increasing endogenous cAMP.

PMID- 1377511
TI  - Steady-state amounts of alpha- and luteinizing hormone (LH) beta-subunit
      messenger ribonucleic acids are uncoupled from pulsatility of LH secretion during
      sexual maturation of the heifer.
AB  - Our primary objective for this study was to determine whether steady-state
      amounts of alpha- and LH beta-subunit mRNAs in the anterior pituitary are altered
      during sexual maturation in the bovine female. A secondary objective was to
      determine whether 17 beta-estradiol (E2) alters amounts of LH subunit mRNAs
      before onset of puberty. Heifers (7 mo old) were assigned to one of three
      treatments: 1) ovariectomized (OVX, n = 16); 2) OVX and administered E2 (OVXE, n
      = 16); or 3) ovary-intact (INTACT, n = 20). Pituitaries were collected at an
      estimated 120 days before onset of puberty (prepuberty) or 25 days before onset
      of puberty (peripuberty). Six INTACT heifers were used to determine time of
      puberty during the experimental period, and their pituitaries were collected 40 h
      after administration of prostaglandin F2 alpha (postpubertal INTACT group).
      Relative amounts of mRNAs for LH subunits in each pituitary were determined by
      Northern analysis and scanning densitometry. Amounts of alpha- and LH beta
      subunit mRNAs were lower in pituitaries of INTACT heifers and OVXE heifers,
      regardless of stage of sexual maturation, than in those of OVX heifers. Amounts
      of alpha-subunit mRNA were similar in OVXE and INTACT heifers regardless of stage
      of sexual maturation. Amounts of LH beta-subunit mRNA did not change during
      sexual maturation in heifers in the INTACT group. Concentrations of E2 were
      higher and LH beta-subunit mRNA were lower in heifers from the prepubertal OVXE
      group than in heifers in all other treatment groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377512
TI  - Anti-RNA polymerase I antibodies in the sera of MRL lupus mice at the initial
      stages of disease are directed primarily against phosphorylation-dependent
      epitopes.
AB  - Anti-RNA polymerase I (RPI) antibodies in the sera of MRL/Mp-lpr/lpr and MRL/Mp(
      )+/+ mice, which develop an autoimmune disease similar to human systemic lupus
      erythematosus, were screened for reactivity with purified RPI or RPI which had
      been dephosphorylated. In every case (n = 10), dephosphorylation of RPI resulted
      in a significant decrease (33-95%) in antibody binding. The anti-RPI antibodies
      in the sera of the same mice approximately 6 weeks later also reacted better with
      untreated as compared to dephosphorylated RPI but, in every case, the decrease in
      antibody (0-30%) caused by dephosphorylation was substantially diminished. That
      the proportion of anti-RPI antibodies in the sera of MRL mice decreased with
      progression of lupus-like disease was confirmed by closely monitoring the
      antibodies over the course of disease. Anti-RPI antibodies produced at the
      earliest stages appeared to be directed almost exclusively against
      phosphorylation-dependent determinants since dephosphorylation of RPI essentially
      abolished antibody binding. Subsequently, the percentage of the total anti-RPI
      antibodies in the sera of these mice directed towards phosphorylation-independent
      epitopes increased linearly with time. The importance of phosphorylation
      dependent epitopes on RPI for the development of the anti-RPI autoimmune response
      was supported by the observation that treatment of mice with alkaline phosphatase
      partially attenuated anti-RPI antibody production.

PMID- 1377513
TI  - Anti-insulin antibody structure and conformation. I. Molecular modeling and
      mechanics of an insulin antibody.
AB  - A knowledge-based three-dimensional model of an anti-insulin antibody, 125, was
      constructed using the structures of conserved residues found in other known
      crystallographic immunoglobulins. Molecular modeling and mechanics were done with
      the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT
      workstation. A minimal model was made by scaffolding using crystallography
      coordinates of the antibody HyHEL-5, because it had the highest amino acid
      sequence homology with 125 (84% light chain, 65% heavy chain). The three
      hypervariable loop turns that are longer in 125 than in HyHEL-5 (L1, L3, and H3)
      were modeled separately and incorporated into the HyHEL-5 structure; then other
      amino acid substitutions were made and torsions optimized. The 125 model
      maintains all the structural attributes of an antibody and the structures
      conserved in known antibodies. Although there are many polar amino acids
      (especially serines) in this site, the overall van der Waals surface shape is
      determined by positions of aromatic side chains. Based on this model, it is
      suggested that hydrogen bonding may be key in the interaction between the human
      insulin A chain loop antigenic epitope and 125.

PMID- 1377514
TI  - The interactions of neuropeptides with membrane model systems: a case study.
AB  - The interactions between the positively charged neuropeptides substance P (SP),
      bradykinin (BK), and zwitterionic Met-enkephalin (ME) neuropeptides, and
      negatively charged SDS and zwitterionic lysophosphatidylcholine (LPC) membrane
      model systems, have been investigated using one- and two-dimensional nmr
      experiments. Proton longitudinal relaxation studies were used to characterize
      these interactions as intrinsic or extrinsic. An extrinsic interaction are
      similar to those observed for extrinsic membrane proteins. An intrinsic
      interaction are similar to those observed for intrinsic membrane proteins, and
      would require that the hydrophobic residues penetrate or insert into the
      hydrophobic core of the membrane. The interactions between both SP and BK and
      SDS, based on nmr results, may be characterized as intrinsic, and the interaction
      between ME and SDS may be characterized as extrinsic. Two-dimensional nuclear
      Overhauser enhancement spectroscopy experiments proved the insertion of the
      phenylalanine residues on both SP and BK into the hydrophobic core of SDS
      micelles. The interaction between SP and BK with LPC based on nmr results are
      characterized as extrinsic, with the interaction between ME and SDS characterized
      as weakly intrinsic.

PMID- 1377515
TI  - Interleukin 4 amplifies monocyte chemotactic protein and interleukin 6 production
      by endothelial cells.
AB  - Upon exposure to interleukin 4 (IL-4), human umbilical vein endothelial cells
      (EC) produced low amounts of IL-6 and expressed low levels of IL-6 transcripts.
      While being a weak stimulus for IL-6 production, IL-4 amplified the release and
      mRNA expression of this cytokine in response to optimal concentrations of IL-1.
      IL-4 also induced low levels of monocyte chemotactic protein but amplified the
      expression of this chemoattractant in response to inflammatory signals. Thus IL
      4, by amplifying at the level of the vascular endothelium the expression of
      vascular cell adhesion molecule 1 selectively, as well as that of
      chemoattractants and IL-6, may favour the selective recruitment and activation of
      lymphoid and monocytic elements crucial for subacute/chronic inflammation and
      immune reactions.

PMID- 1377516
TI  - Inhibitory effect of recombinant intracellular interleukin 1 receptor antagonist
      on endothelial cell activation.
AB  - This investigation was designed to elucidate whether an intracellular version of
      interleukin 1 receptor antagonist (icIL-1ra) interferes with the action of IL-1
      at the level of vascular cells. Recombinant icIL-1ra inhibited the IL-1-induced
      production of IL-6, IL-8 and monocyte chemotactic protein by human endothelial
      cells (HEC). Moreover, icIL-1ra inhibited induction of adhesion molecules by IL
      1. Endotoxin lipopolysaccharide (LPS), an IL-1 inducer, stimulated a spectrum of
      functions in EC similar to that activated by IL-1, but icIL-1ra did not interfere
      with the LPS activation of EC. This observation suggests that induction of
      extracellular IL-1 is not an important intermediate event in the response of EC
      to LPS. Unlike LPS-stimulated monocytes, EC exposed to different inducers did not
      express appreciable levels of IL-1ra mRNA transcripts as assessed by northern
      blot analysis. IL-1ra produced by mononuclear phagocytes, represents a negative
      regulator circuit of the action of IL-1 on EC and could be important in the
      control of vascular participation in inflammation and immunity.

PMID- 1377517
TI  - Immune surveillance against Epstein-Barr virus.
AB  - Following primary infection, EBV retains a life-long latent association with B
      lymphocytes and a permissive association with stratified epithelium in the
      oropharynx. This review presents a model for the host-virus relationships in
      healthy virus carriers, a relationship which, if perturbed, may result in EBV
      associated disease. Cytotoxic T cells that recognise virally-determined epitopes
      on infected cells are the major effector arm and control the persistant
      infection. A strategy for developing a vaccine to EBV is discussed.

PMID- 1377518
TI  - [Metallic mesh endoprosthesis and intraluminal high dose rate 192Ir brachytherapy
      in the palliative treatment of malignant bile duct obstruction. Initial results].
AB  - Since December 1989, 9 patients with inoperable malignant biliary tract
      obstruction were treated palliatively by a combined modality treatment consisting
      of placement of a permanent biliary endoprosthesis followed by intraluminal high
      dose-rate 192Ir brachytherapy. A dose of 10 Gy was delivered in a
      hyperfractionated schedule at the point of reference in a distance of 7.5 mm of
      centre of the source. External small field radiotherapy (50.4 Gy, 1.8 Gy per day,
      5 fractions per week) was also given in six cases (M/O, Karnofsky greater than
      60%). In 9/9 cases an unrestrained bile flow and an interruption of pruritus was
      achieved, in 78% (7/9) of cases the duration of palliation was as long as the
      survival time (median survival time 7.5 months).

PMID- 1377519
TI  - Deployment of extracellular matrix proteins in sea urchin embryogenesis.
AB  - The apical extracellular matrix of the sea urchin embryo, known as the hyaline
      layer (HL), is a multi-laminate organelle composed of at least 10 polypeptides.
      Although integrated into one ECM, HL proteins exhibit individual temporal and
      spatial dynamics throughout development. These molecules are stockpiled in the
      oocyte during vitellogenesis in at least four distinct vesicle populations. They
      are released onto the cell surface at fertilization in a specific order, and
      interact differentially with embryonic cells as development proceeds. Many
      experiments have suggested that the HL is vital for embryogenesis, but relatively
      little is known about the functions and interactions of its constituent
      molecules. The purpose of the present review has been to gather information on
      the basic characteristics of the known HL proteins together with data on their
      expression in the embryo, and where possible, their biological activities.
      Compiled, these observations may provide some insight into the workings of a
      uniquely embryonic organelle.

PMID- 1377520
TI  - Characterization of insulin-like growth factor receptors in the insulin
      responsive R3230AC mammary adenocarcinoma.
AB  - To ascertain whether insulin-like growth factors (IGF-1 and IGF-2) affect the
      estrogen- and insulin-responsive R3230AC mammary carcinoma, studies of IGF-1 and
      IGF-2 receptors were conducted on primary-culture tumor cells and on membranes
      purified from whole tumors. By saturation binding analysis, cells in culture
      displayed one class of IGF-1 binding sites with an affinity constant, Kd, of 5.5
      +/- 0.7 x 10(-9) M, whereas in membrane preparations, high and low affinity IGF-1
      binding sites, with Kd's of 5 +/- 1.7 x 10(-9) M and 1 +/- 0.4 x 10(-7) M,
      respectively, were detected. Specificity of binding was demonstrated by 85%
      displacement of 125I-IGF-1 with 1,000-fold excess unlabeled IGF-1 and 50%
      displacement with 6.5 x 10(-9) M IGF-1 or 3 microM insulin. Binding sites for IGF
      2 were also demonstrable in cultured cells, having a Kd of 7 +/- 0.8 x 10(-10) M,
      and 50% displacement was obtained with 1.5 x 10(-9) M IGF-2 or 1.5 x 10(-8) M IGF
      1. Cross-linking experiments on cultured cells confirmed the presence of IGF-1
      and IGF-2 receptors. In purified tumor membranes, IGF binding proteins (M(r)
      28,000-32,000) were also detected; their labeling was not displaced by 10(-5) M
      insulin. In vitro, the tumor cells secrete one or more IGF binding proteins into
      the medium. Despite the fact that these cells expressed specific IGF receptors,
      their growth was apparently independent of these growth factors, since neither
      IGF-1 nor IGF-2 was mitogenic for R3230AC cells in vitro. Nevertheless, IGF-1
      caused concentration-related significant increases in the plating efficiency of
      these cells. Further studies are necessary to determine the functional role of
      these growth factors, their receptors, and their binding proteins in the biology
      of this rodent mammary tumor.

PMID- 1377522
TI  - Angiogenesis: key principles, science, technology, medicine.

PMID- 1377521
TI  - Angiogenesis--historical perspective.

PMID- 1377524
TI  - Endothelial cell migration and chemotaxis in angiogenesis.
AB  - Our goal has been to provide a quantitative analysis of the random motility and
      chemotaxis of microvessel endothelial cells (MEC) in order to understand the role
      of these functions in the development of new capillaries. A major difference of
      our work from previous investigations has been our use of mathematical analysis
      to interpret experimental results, and to relate in vitro migration measurements
      to in vivo angiogenesis observations. In this paper we present some of our
      methods and their rationale, with recent results from both experiment and
      mathematical models.

PMID- 1377523
TI  - Angiogenesis and heparin mimics.

PMID- 1377525
TI  - Microenvironment and angiogenic response.

PMID- 1377526
TI  - Modulation of angiogenesis in vitro.

PMID- 1377527
TI  - Proteolytic balance and capillary morphogenesis in vitro.

PMID- 1377528
TI  - Angiogenesis--the interdisciplinary challenge.

PMID- 1377529
TI  - Metalloproteinase inhibition as a mechanism for the inhibition of angiogenesis.

PMID- 1377530
TI  - Differential expression of integrin cell-substratum adhesion receptors on
      endothelium.
AB  - The interactions of the endothelial cells with their underlying extracellular
      matrix is of fundamental importance to angiogenesis. Therefore, the distribution
      of integrin cell-substratum adhesion receptors on cultured and in situ
      endothelial cells was determined. Cultured endothelium from large and small
      vessels and large vessel endothelial cells in situ expressed integrins that bound
      to both basement membrane and inflammatory matrix components. In contrast, in
      situ microvessels primarily expressed basement membrane binding integrins.
      Alterations in the expression of the integrins on microvessel endothelial cells
      may be important for microvascular remodeling during wound healing and/or
      angiogenesis.

PMID- 1377531
TI  - Angiogenesis--cytokines as part of a network.

PMID- 1377532
TI  - Binding sites for basic fibroblast growth factor on solid tumors are associated
      with the vasculature.

PMID- 1377533
TI  - Studies on basic fibroblast growth factor (FGF-beta) gene expression in the rat
      and pig ovary using in situ hybridization and quantitative reverse transcriptase-
      polymerase chain reaction techniques.
AB  - In order to gain further understanding of the physiology of basic fibroblast
      growth factor (FGF-beta) in the mammalian reproductive tract, the expression of
      FGF-beta mRNA in the rat and porcine ovary has been examined by in situ
      hybridization and quantitative reverse transcriptase-polymerase chain reaction
      techniques during different stages of the estrus cycle. The results confirm that
      an increase in FGF-beta mRNA levels occurs over the course of the estrus cycle.
      No FGF-beta gene expression was detected during diestrus, the non-hormonal phase
      of the cycle, or at the early proestrus stage of the cycle. During late proestrus
      and estrus, FGF-beta mRNA was predominantly localized to granulosa cells of the
      dominant follicles, and to a lesser extent, to secondary antral follicles not
      committed to ovulation. These cells also expressed FGF-beta mRNA during this
      phase of follicular development, albeit in low abundance. During metestrus, after
      ovulation, in the newly formed corpora lutea FGF-beta mRNA levels were maximal,
      however on entering the next cycle commencing at diestrus, no FGF-beta mRNA was
      observed in the degenerating corpora lutea. These results indicate that
      expression of the FGF-beta gene is differentially regulated during the estrus
      cycle. The biological significance of this expression and the potential role of
      FGF-beta in local intra-ovarian regulation of the repetitive cycles of follicular
      differentiation, proliferation and maturation associated with ovarian
      revascularization are discussed.

PMID- 1377534
TI  - Angiogenesis--biomedical technology.
AB  - All of these studies show that angiogenesis research can benefit from new
      biomedical technology tools currently being developed, as well as contribute by
      providing new technologies that can be used in other areas of medicine. It is
      hoped that the chapters in this book in this area will provide the reader with an
      up-to-date appreciation of some of the exciting research that is currently being
      pursued.

PMID- 1377535
TI  - Angiogenin and endothelial cells.

PMID- 1377536
TI  - Cultured endothelial cell mobilization induced by partially purified human
      uterine angiogenic factor.

PMID- 1377537
TI  - Two cloned cerebral endothelial cell phenotypes: an in vitro model for
      angiogenesis?
AB  - Expression of smooth muscle alpha-actin and migratory behaviour of cloned
      cerebral endothelial cells (cEC) which exhibited two distinct phenotypes (type I,
      type II) were studied. Removal of mitogenic factors (alpha ECGF, ECGS) and
      heparin from the culture medium resulted in a smooth muscle-like appearance (type
      II) of the cells, expression of smooth muscle alpha-actin protein and smooth
      muscle actin mRNA and in an increased migratory activity. In contrast, addition
      of growth factors and heparin led to a cobblestone-like phenotype (type I) which
      lacked the expression of smooth muscle alpha-actin but expressed other proteins
      as determined by 2-D-gel electrophoresis.

PMID- 1377538
TI  - Bone endothelial cells: a tool for analyzing cell to cell interactions in the
      skeletal tissue.

PMID- 1377540
TI  - Angiogenesis--time to review progress.

PMID- 1377539
TI  - Expression of angiogenic growth factors in the collateralized swine myocardium.

PMID- 1377541
TI  - Tumor cell spheroids induce a mitogenic response in endothelial cells.
AB  - Conditioned media from spheroids of human colorectal tumor cell lines HT29,
      SW620, SW480 and CaCo-2 were tested for their mitogenic activity on human
      umbilical vein endothelial (HUVE) and bovine capillary endothelial (BCE) cells.
      All spheroid-conditioned media were capable of increasing the labeling indices in
      both endothelial cell populations, with the mitogenic activity decreasing in the
      following order: SW620, HT29/SW480 and CaCo-2. The endothelial cell mitogenic
      activity of the spheroids was not dependent on the presence of necrosis nor on
      their in vivo cytokinetic characteristics. We conclude that tumor spheroids
      release mitogenic activity for endothelial cells, but this stimulation depends on
      the age of the tumor spheroid as well as on the type of tumor used.

PMID- 1377542
TI  - A monoclonal antibody (E-9) binds preferentially to the vasculatures of human
      tumors, embryonic and regenerating tissues.

PMID- 1377543
TI  - Induction and altered distribution of tenascin in the basal lamina of colorectal
      adenomas and carcinomas.

PMID- 1377544
TI  - On the quantitative rat mesenteric-window angiogenesis assay.
AB  - The rodent mesenteric-window angiogenesis assay permits the quantitative
      assessment of angiogenesis in adult, normally-vascularized mammalian tissue in
      the intact animal. Using appropriate optical magnifications, even very small,
      newly-formed vessels are recorded. The ultimate value of the model will, of
      course, depend on how pertinent it is to the features which govern angiogenesis
      in the tissues that are involved in clinically-relevant, angiogenesis-related
      diseases.

PMID- 1377545
TI  - Wound healing in aged animals--effects of locally applied transforming growth
      factor beta 2 in different model systems.
AB  - Local application of a growth factor which could stimulate cell turnover,
      extracellular matrix synthesis and blood vessel formation in the skin should
      improve and accelerate wound healing processes which are often impaired in old
      age. We demonstrate the effects of TGF-beta 2 in promoting wound repair in old
      animals where normal healing responses are shown to be naturally slower. The
      potential use of TGF-beta s for the treatment of wound injuries, including
      chronic non-healing ulcers in the elderly, is discussed.

PMID- 1377546
TI  - Angiogenesis--a new fascinating enigma for surgeons?!

PMID- 1377548
TI  - Angiogenic activity of PAF and inhibition of blood flow by Bothrops Jararaca
      venom in a mouse sponge model.

PMID- 1377547
TI  - Intradermal angiogenesis in nude mice induced by human tumor cells or b-FGF.

PMID- 1377549
TI  - Further studies on angiogenesis in a rat sponge model.

PMID- 1377550
TI  - A multichannel wounding device for the study of vascular repair in vitro.

PMID- 1377551
TI  - Assessment of angiogenic potential--the use of AIDS-KS cell supernatants as an in
      vitro model.

PMID- 1377552
TI  - Delivery systems for angiogenesis stimulators and inhibitors.
AB  - The development of biocompatible, controlled release systems for macromolecules
      has provided the opportunity to deliver angiogenesis stimulators and inhibitors.
      These systems have also facilitated the purification and characterization of a
      number of these substances. In this paper, we discuss controlled release delivery
      systems which release angiogenesis factors through either porous polymer
      matrices, degradable polymeric delivery systems or modulated polymer release
      systems.

PMID- 1377554
TI  - Angiogenic vessels as a potential for targeted therapy in human liver metastases.

PMID- 1377553
TI  - Angiopolarity of cell carriers: directional angiogenesis in resorbable liver cell
      transplantation devices.
AB  - The purpose of this study was to obtain directional angiogenesis of small blood
      vessels and capillaries to an implant made from a resorbable polymer for
      hepatocyte transplantation. It was intended to mimic the native acinar structure
      of the liver in order to facilitate replication of the cells and organ growth.
      The implant device structure was designed for injection to minimize surgical
      trauma. Hollow microspheres with an open porous wall structure and one large
      central opening were made from poly(d,l-lactic-co-glycolic acid) (85:15
      lactic:glycolic). This polymeric scaffold was seeded with hepatocytes and
      implanted into the abdominal wall muscle of syngeneic Fisher rats. Specimens
      explanted up to 56 days p.o. showed hepatocyte survival and the development of a
      directional blood supply. This phenomenon is coined "angiopolarity". The study
      should help in addressing the issue as to whether avascular cell implants with
      post-transplantation organ growth should be attempted. Processing options in
      applying heat to the polymer solution allow manufacturing of larger microspheres
      with different diameters of central openings. This would allow the use of the
      scaffold for other cell transplantations than hepatocytes.

PMID- 1377555
TI  - Deuterium nuclear magnetic resonance imaging of the developmental pattern of
      tumour blood flow.

PMID- 1377556
TI  - The perfluorocarbon emulsion PFOB: potential indicator of change in blood volume
      using fluorine-19 NMR spectroscopy.

PMID- 1377557
TI  - Clinical investigations on blood perfusion in human malignancies of the pelvis
      and abdomen: significance for tumor therapy.
AB  - Blood flow of deep pelvic and abdominal tumors was investigated with the thermal
      clearance method, dynamic CT and dynamic MRI. There are good correlations between
      the measurement values obtained by these methods. A low flow was observed in
      rectal cancer and soft tissue sarcoma in contrast to pancreatic cancer and
      hypernephroma. The temperature increase induced by regional hyperthermia was
      dependent on the individual tumor blood flow. Dynamic CT can be used
      pretherapeutically and predict the quality of a heat treatment, which is
      important with regard to concepts consisting in radiotherapy or chemotherapy plus
      hyperthermia.

PMID- 1377558
TI  - Induction of angiogenesis by growth factors: relevance to pancreatic islet
      transplantation.
AB  - Biodegradable pellets releasing 20 ng/day of endothelial cell growth factor alpha
      (alpha ECGF) or a- or b-fibroblast growth factor (FGF) and 90 micrograms/day of
      heparin were implanted beneath the renal capsule in rats and dogs and the
      muscularis/serosal border of the pyloric stomach in dogs to test for angiogenesis
      in a potential pancreatic islet transplant site. These factors were also tested
      in vitro to determine whether the capillary bed of the isolated islet could be
      preserved. alpha ECGF was superior to a- or bFGF in promoting endothelial cell
      growth and capillary formation in isolated islets. Both a- or bFGF and alpha ECGF
      induced the development of a dense capillary bed in the dog stomach, whereas in
      the kidney site alpha ECGF was more effective in the rat than was a- or bFGF.
      Priming the isolated islet as well as the transplant site prior to islet
      transplantation resulted in islet blood flow being established within 3 days in
      contrast to 7-14 days in controls.

PMID- 1377559
TI  - Capillary growth in the heart.
AB  - Experiments were performed to test the hypothesis that increased stretch and/or
      tension of myocytes in the absence of changes in blood flow could induce
      capillary growth in the heart. Chronic treatment with either dobutamine (rabbits)
      or alinidine (rats) which increased force of contraction and/or stroke volume
      respectively without increases in coronary blood flow led to enlargement of the
      anatomical size of the capillary bed, with no change in cardiac weight, thus
      supporting the role of external mechanical factors in angiogenesis.

PMID- 1377561
TI  - Angiogenesis--retrospect and outlook.

PMID- 1377560
TI  - Angiogenic role of lactic acid in the mechanism of neovascularization.

PMID- 1377562
TI  - Combined morphological approaches in the study of network formation in tumor
      angiogenesis.

PMID- 1377564
TI  - Impact of basic fibroblast growth factor (bFGF) on wound healing in chronically
      ischemic tissue.

PMID- 1377563
TI  - Hyperoxia (145 mmHg pO2) and tissue normoxia (20-40 mmHg pO2) modulate human
      vascular cell functions.

PMID- 1377565
TI  - Endothelial cell proliferation is induced by radiation in cultured explants of
      human urothelium and oesophageal mucosa.
AB  - Normal oesophageal mucosa obtained during upper abdominal surgery or urothelium
      obtained from kidney transplants was placed in explant culture and exposed to
      60Co gamma radiation after 48 h. Cultures were maintained for two to six weeks
      after exposure and were monitored at various intervals for the development of
      features associated with malignant transformation. Endpoints examined included
      proliferation rate, frequency of proliferating cells, cell type distribution and
      degree of differentiation of the different cell types. The results indicate that
      following exposure to gamma rays (2.5-10 Gy) an increased overall growth rate of
      the surviving cells can be observed 2-4 weeks later. Analysis of the results
      using autoradiography confirms that a higher level of cell proliferation occurs
      in treated cultures than in the control untreated cultures. When the distribution
      of different cell types in the culture is examined, the increase in growth can be
      seen to be due to greatly increased numbers of endothelial cells. These
      proliferated over the surface of the epithelial cells and are more strongly
      positive for endothelial cells markers than endothelial cells occurring in
      control cultures. The degree of differentiation of endothelial cells into
      capillary like structures is also more apparent in carcinogen treated cultures.
      Foci expressing both epithelial and endothelial markers also occur. The results
      suggest that exposure of tissue fragments to radiation stimulates the growth and
      development of endothelial cells in resulting cell cultures. The effect may be
      due to a direct action of the treatment on the endothelial cells but it is more
      likely that it results from a secondary effect mediated by traumatic response of
      damaged epithelial cells.

PMID- 1377566
TI  - Angiogenesis during tumor progression in human malignant melanoma.

PMID- 1377567
TI  - A protein RNase inhibitor (RNasin) expresses anti-angiogenic properties in mice.

PMID- 1377568
TI  - Studies on tumor induced angiogenesis.
AB  - Methods were developed to test angiogenic response to human tumor implants and
      various biologic agents in the cornea of rabbits and non-human primates (Macaca
      arctoides). Crude PDGF preparations were found to have significant angiogenic
      effect. Purified, recombinant PDGF preparations were also effective inhibitors
      (e.g. pentoxifylline (Px) (which also were found to release PgI2 and t-PA)
      inhibited human tumor implant induced angiogenesis and reduced spontaneous
      metastases in 3 transplantable murine tumors (Furth-Columbia Wilms' tumor in
      Furth-Wistar rats, C-1300 neuroblastoma in A/J mice and HM-Kim mammary carcinoma
      in Wistar rats) but not in the NIH adenocarcinoma in Balb/c mice. Sodium
      diethyldithiocarbamate (DDTC), a metal complexing agent with special affinity to
      copper and anti-thyroid as well as, immune stimulating activity was shown to be
      anti-angiogenic and to potentiate the effect of Px. The anti-fibrinolytic agents
      epsilon amino caproic acid (EACA) and tranaxamic acid (t-AMCHA) were anti
      angiogenic. DDTC and Px were synergistic from this point of view.

PMID- 1377569
TI  - The mode of action of anti-angiogenic steroid and heparin.

PMID- 1377570
TI  - Angiostatic activity of anticancer agents in the chick embryo chorioallantoic
      membrane (CHE-CAM) assay.
AB  - Most anticancer agents are screened for antiproliferative and differentiation
      inducing activity on tumor cells, but not for differential effects on vascular
      endothelium. Clinically active cytotoxic or cytostatic agents and selected
      analogs were tested in a closed, ethically accepted and inexpensive in vivo
      fertilized egg system [CHE-CAM]. The results revealed characteristic effects on
      vessel numbers between day 7 and 11 and on embryo weight at day 12. Hitherto
      unknown angiostatic activities were discovered with antitumor antibiotics, plant
      alkaloids, antimetabolites and other classes of compounds. The information
      provided by the CHE-CAM assay could represent a valuable complementation to the
      existing drug-screening systems for solid tumors and suggests a selective
      angiostatic role of some antitumor agents currently used in combination
      treatments.

PMID- 1377571
TI  - In vitro activity of novel sulphonic derivatives of distamycin A.
AB  - The successful growth of tumors is dependent on the process of vascularization
      elicited by the tumor itself. As confirmed by many authors, there is a
      correlation between the presence of factors that stimulate tumor growth and
      angiogenesis. One of the approaches we have explored to control angiogenesis has
      been to synthesize compounds able to complex growth factors. A number of
      sulphonated derivatives of distamycin A were found active in inhibiting the
      binding of bFGF and PDGF beta on Swiss 3T3 cells with ID50 values ranging between
      142-587 microM for bFGF and 28-79 microM for PDGF beta. The effect of these new
      derivatives in inhibiting angiogenesis was initially explored in the
      chorioallantoic membrane assay. It was observed that the selected compounds were
      active in this model system at the concentration of 350 nm/pellet. These new
      molecules present low or no cytotoxic activity on M5076 murine reticulosarcoma
      cells, the ID50 values being higher than 60 microM after 72 h continuous exposure
      in vitro.

PMID- 1377573
TI  - Antiangiogenesis strategies in cancer therapy with special reference to Krestin.

PMID- 1377574
TI  - Angiogenesis in MEDLINE and beyond.

PMID- 1377572
TI  - In vivo activity of novel sulphonic derivatives of distamycin A.
AB  - Solid tumor growth can be modulated through inhibition of vascularization
      elicited by angiogenic factors. With the objective to complex these factors, new
      derivatives of distamycin A were synthesized and evaluated in vitro [1] and in
      vivo for their ability, after i.v. administration, to inhibit bFGF-induced
      vascularization and the growth of M5076 murine reticulosarcoma implanted i.m. The
      tested compounds were able to block angiogenesis with inhibition values ranging
      between 70-100%. Moreover, they were found to be capable of inducing tumor
      inhibition with values ranging between 40% and 95% at non-toxic doses.

PMID- 1377575
TI  - Maturation of newly-formed subretinal vessels.
AB  - The maturation process of newly-formed subretinal vessels was studied
      ultrastructurally. Primitive new vessels have thick endothelial cells with
      cytoplasm that contains many ribosomes and rough endoplasmic reticulum. Some
      immature endothelial cells show budding, and many of the intercellular junctions
      have small gaps. As the newly-formed vessels mature, the endothelial cells become
      attenuated and fenestrated, and their junctions become tight. Mature subretinal
      new vessels closely resemble those of the normal choriocapillaris.

PMID- 1377577
TI  - Vascular supply in embryonic neural transplants.

PMID- 1377576
TI  - Embryonic development of the CNS microvasculature in the mouse: new insights into
      the structural mechanisms of early angiogenesis.
AB  - Vascularization and expression of blood-brain barrier (bbb) associated
      morphological characteristics were studied by ultrastructural analysis during the
      embryonic development of the mouse CNS. At day 9 (E9) capillaries were only found
      in the perineural mesenchymal tissue exhibiting fenestrations and loosely
      attached pericytes. At E10 endothelial cells (EC) together with pericytes and
      other mesenchymal cells invaded the intraneural domain. The immigrating EC showed
      numerous protrusions and lost their fenestrations as soon as the new intraneural
      capillaries were formed. Intraneural EC showed prominent nuclei, many pinocytotic
      vesicles and junctional complexes which appeared tight in some places. These
      results indicate that from the first day of intraneural vascularization onwards,
      the morphological properties of the bbb are present in the early embryonic mouse
      cerebral cortex.

PMID- 1377578
TI  - Microvascular network architecture in a mammary carcinoma.

PMID- 1377579
TI  - Tumor angiogenesis: evidence of new blood channels from plasma infiltrations.
AB  - Stroma formation in Ehrlich carcinoma, studied with histochemical and TEM
      techniques, is similar to wound healing. In this tumour mast cells, macrophages,
      adipocytes, platelets and fibrin seem to co-operate locally with malignant cells
      in regulating stroma formation. The gaps opened in the tumor parenchyma by plasma
      outpouring from local blood vessels seem to offer easy routes for endothelial
      cell migration towards ill-nourished areas, and may explain the irregular aspect
      of tumor microvascularity.

PMID- 1377580
TI  - Hemopoietic stem cell processing: comparison of progenitor cell recovery using
      the Cobe 2991 cell washer and the Haemonetics V50 apheresis system.
AB  - Using 24 bone marrow (BM) harvests intended for cryopreservation and
      transplantation, we compared the use of the Cobe 2991 cell washer (2991) and the
      Haemonetics V50 apheresis system (HV50) for automated BM processing. Our in vitro
      data indicate that while the mononuclear cell (MNC) concentration of the HV50
      product was significantly greater than that of the 2991, the overall MNC recovery
      of the two products was equivalent. In addition, although the concentration of
      CFU-GM and BFU-E in the products was equivalent, recovery of these progenitors in
      the 2991 product was significantly greater than those of the HV50 product. There
      was no significant difference in either the final product concentration or the
      overall recovery of cells bearing the primitive myeloid antigens, CD33 or CD34,
      between the two methods. The HV50 product volume, the red cell and the
      granulocyte mass were significantly lower than those of the 2991. We conclude
      that the advantages gained through the use of each machine should be evaluated
      within the context of the specific intention for the graft. Future advances in
      the identification and understanding of the primitive stem cell will aid in
      attempts to evaluate the methods used to isolate these cells.

PMID- 1377581
TI  - Psychiatric assessment of chronic pain.

PMID- 1377582
TI  - Serotonin, eating disorders, and HIV infection.

PMID- 1377583
TI  - A morphometric analysis of trimethyltin-induced change in rat brain using the
      Timm technique.
AB  - Rats were given a single gavage of trimethyltin chloride (TMT) providing a dose
      of 0, 4.3, or 6.7 mg/kg of alkyltin. Gross changes in brain structures were
      quantified and analyzed statistically. Behavioral and functional measures were
      taken to verify efficacy of TMT dose. The high dose produced transient weight
      loss and seizures. In the fourth week after gavage, the high dose produced
      hyperactivity in the residential maze and activity wheel. High and low TMT doses
      decreased auditory startle responsiveness. Estrus cycle was normal in all groups.
      Brains were sectioned and stained with the Timm stain which delimited subregions
      of hippocampus and connected structures and also revealed mossy fibers. Linear
      and areal measures were made at three positions along the septotemporal axis of
      Ammon's horn. The low dose produced reductions in size in a few isolated subareas
      of the brain. The high dose produced, at the three planes studied, extensive (15
      40%) loss of tissue in Ammon's horn and structures to which Ammon's horn is
      interconnected--subiculum, entorhinal cortex, dentate gyrus, hilus, CA3, and CA1
      region. Neocortex and caudate-putamen were unaffected. These findings suggest
      that a single TMT gavage may disrupt brain structures important to linking
      neocortex with subcortex via structures in the hippocampal region.

PMID- 1377584
TI  - Substance P synaptic interactions with GABAergic and dopaminergic neurons in rat
      substantia nigra: an ultrastructural double-labeling immunocytochemical study.
AB  - The distribution of substance P (SP), tyrosine hydroxylase (TH), and glutamic
      acid decarboxylase (GAD) immunoreactivity in the substantia nigra of the rat was
      studied by means of an ultrastructural double-labeling immunocytochemical method.
      Direct synaptic contact between SP-immunoreactive terminals and GAD-positive
      nigral neurons was more often observed in the pars lateralis than the pars
      reticularis and was rarely observed in the pars compacta. Substance P-positive
      terminals also formed synapses with cell bodies and dendrites of TH-positive,
      dopaminergic neurons in the pars compacta and pars reticulata. Multiple SP
      immunoreactive terminals were often observed with symmetrical and, less
      frequently, asymmetrical synapses on individual TH-containing dendrites. Evidence
      of SP-containing terminals contacting both GABAergic and dopaminergic neurons in
      the substantia nigra suggests a direct excitatory action upon nigral projection
      neurons.

PMID- 1377585
TI  - Neuropeptides in the torus semicircularis of the carp (Cyprinus carpio).
AB  - The distribution of fibers and cell bodies containing neurotensin, neurokinin A,
      galanin, or somatostatin-28(1-12) immunoreactivity in the torus semicircularis of
      the carp was studied using an indirect immunoperoxidase technique. In this
      mesencephalic region, a high-density of galanin-immunoreactive fibers was found,
      whereas neurokinin A or somatostatin-28(1-12)-immunoreactive processes were
      observed at a moderate density and neurotensin-immunoreactive fibers at a low
      density. Cell bodies containing somatostatin-28(1-12) immunoreactivity were
      observed in both central and lateral nuclei. The torus semicircularis was not
      immunoreactive for dynorphin A. The presence of these neuropeptides in the carp
      torus semicircularis suggests that such neuroactive substances may be involved in
      auditory and visual mechanisms, as well as in the control of inputs arising from
      the lateral line system.

PMID- 1377586
TI  - Efferent projections of the nucleus raphe magnus.
AB  - This study was performed to identify supraspinal efferents of the nucleus raphe
      magnus (NRM) in the rat using the anterograde tracer phaseolus vulgaris
      leucoagglutinin (PHA-L). NRM-derived PHA-L-ir fibers, with putative terminals,
      were identified in regions including the lateral hypothalamus, parafascicular
      nucleus, ventral lateral periaqueductal gray (PAG), locus coeruleus, parabrachial
      nucleus, A7, A5, and nucleus tractus solitarius. Projections to the PAG
      demonstrate reciprocity in PAG-NRM connectivity that may modulate the PAG-NRM
      spinal cord pathway. The NRM may contribute to supraspinal modulation of
      nociception by efferents identified in the PAG, as well as locus coeruleus, A7,
      and A5, which have been shown to project to the spinal cord dorsal horn. Our
      results provide neuroanatomical support for NRM involvement in supraspinal
      mechanism(s) for modulation of nociception.

PMID- 1377587
TI  - In vivo measurement of hypothalamic serotonin release by intracerebral
      microdialysis: significant enhancement by immobilization stress in rats.
AB  - Intracerebral microdialysis was used to measure extracellular serotonin and its
      metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hypothalamus of
      unanesthetized rats. Increase in the concentration of K+ in the perfusing Ringer
      solution (70 mM) produced a sharp increase in serotonin release, which was
      significantly attenuated by omitting Ca2+ from the perfusion medium.
      Intraperitoneal injection of 5-hydroxytryptophan, a precursor of serotonin, or
      local perfusion of pargyline, a monoamine oxidase inhibitor, elevated the
      hypothalamic serotonin. Releasers or uptake inhibitors of serotonin, such as
      fenfluramine, cocaine, mazindol, or imipramine, when added to the perfusion
      medium, significantly increased serotonin level, whereas 5-HIAA was unaffected by
      these substances. Immobilization-stress caused an immediate increase in both the
      extracellular serotonin and 5-HIAA in the hypothalamus, suggesting that the
      hypothalamic serotonergic system is activated during immobilization stress. The
      present study indicates that the brain microdialysis is useful for analysis of
      local changes in serotonin concentration which directly reflect neuronal
      transmission.

PMID- 1377588
TI  - The superior cervical ganglion: origin of sympathetic fibers in the facial and
      hypoglossal nerves in the cat.
AB  - Location of superior cervical ganglion (SCG) neurons, sending axons into the
      facial and hypoglossal nerves, was investigated in the cat by means of retrograde
      axonal transport of horseradish peroxidase (HRP). After wheat germ agglutinin
      conjugated HRP (WGA-HRP) was injected into these nerves, many retrogradely
      labeled neurons were found widely in the ipsilateral SCG, particularly around the
      caudal half of the SCG. These neurons were round or oval in shape and 70-80% of
      these were medium in size. In fluorescent experiments, fast blue (FB) was used in
      combination with diamidino yellow (DY). After injections of FB into the facial
      nerve and DY into the hypoglossal nerve, a few FB-DY double-labeled neurons
      occurred in the SCG ipsilaterally.

PMID- 1377589
TI  - Progressive accumulation of large aggregates of calcium-containing
      polysaccharides and basophilic debris within specific thalamic nuclei after
      lithium/pilocarpine-induced seizures.
AB  - Between 30 and 50 days after the induction of seizures by a single injection of
      lithium and pilocarpine, large aggregates of Nissl-staining material appeared;
      they occupied up to 35% of the thalamic volume. Both histochemical and atomic
      absorption analyses indicated elevated concentrations of Ca++ (and possibly Mg++)
      within this substance that was also composed of polysaccharides and nucleic
      acids. Significant interactions between time since seizure induction and form of
      the material indicated a progressive accretion of this material from diffusely
      scattered micrometer granules to large crystalline forms. We suggest this
      material is composed of endoplasmic reticular debris that is bound by bivalent
      cations; because the severity of damage exceeds local phagocytic capacity, the
      material aggregates and then crystallizes. Possible relation to thalamic
      calcification in neonatal ischemic brains is considered.

PMID- 1377590
TI  - [Prospective study on the diagnosis of hepatocellular carcinoma by using alpha
      fetoprotein reactive to lentil lectin].
AB  - Levels of alpha-fetoprotein reactive to lentil lectin (AFP-R-L) were monitored in
      27 patients with 20-400 micrograms AFP/L and negative imaging. These cases
      finally were proven to be affected by hepatocellular carcinoma. AFP-R-L above 25%
      was used to define the positive result for hepatocellular carcinoma. The
      positivity of AFP-R-L was 63%. At the same time, AFP-R-L was detected in 71 cases
      of chronic liver diseases. All but one had negative AFP-R-L values. The results
      suggested that AFP-R-L could make a dissection 3-28 months earlier than positive
      imaging. An accuracy of predicting hepatoma with positive AFP-R-L was 94%. So the
      diagnosis of hepatoma with negative imaging could be early made by measurement of
      AFP-R-L.

PMID- 1377591
TI  - Angiogenesis in atherosclerosis.
AB  - This article reviews studies on the structure, complications and pathogenesis of
      angiogenesis in atherosclerotic plaques. Although important, this topic has not
      been studied extensively; the authors present a review of the important
      information available in the literature. Since angiogenesis has profound clinical
      complications, the focus is on data which provided information to understand the
      nature of the vascular structures involved and the sequence of events which led
      to the initiation and growth of these small vessels in the plaque. This review
      indicates that it is most likely that the capillaries that first form arise from
      the vasa vasorum. Since the cell biology literature suggests that angiogenesis is
      regulated by angiogenic factors which stimulate vascular cell migration and
      proliferation, the known role of several growth factors and inhibitors is
      reviewed. It is likely that a complex interaction in the atherosclerotic vessel
      wall results in angiogenesis, and that further study with purified growth factors
      and other substances is needed to clarify the pathogenesis of this important
      biological process.

PMID- 1377592
TI  - Intracellular kinetics of the activator calcium of rat heart after ischemic
      arrest and cardioplegia: quantitative comparison of right and left ventricles.
AB  - The effects of plain ischemia (34 degrees C) and the protective role of
      hypothermia (20 degrees C) alone or in combination with cardioplegia (St Thomas'
      Hospital [STH] or glucose-potassium-nifedipine [GPN]) on the intracellular
      kinetics of the activator calcium of cardiac muscle were quantified and compared
      from the interval-force behaviour (mechanical restitution) of right and left
      ventricles of the perfused rat heart. Plain ischemia caused a major depression in
      the restitution of force of contraction of both ventricles, deranged the mixed
      linear-exponential functions by significantly increasing the time constants of
      the fitted mechanical restitution curves (MRC) and altered the control right/left
      ventricle interval-force relationship. The right ventricle was found to be more
      susceptible to ischemic damage than the left ventricle, and its inotropic reserve
      was virtually abolished by 1 h of plain ischemia. Hypothermic preservation during
      ischemia improved the mechanical restitution, salvaged the inotropic reserve and
      optimized right/left ventricle interval-force relationship, but the time
      constants of the fitted MRCs were still prolonged. However, both the cardioplegic
      formulations were equally effective in normalizing the time constants of the
      fitted curves. In general, right ventricle functions were better preserved by STH
      cardioplegia and left ventricle functions were better preserved by GPN
      cardioplegia. Cardioplegic interventions did not further improve the ventricular
      inotropic reserve compared with hypothermic preservation. Additional beneficial
      effects of cardioplegic formulations were directed towards stabilizing the linear
      exponential functions and hence restitution of force of contraction.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377593
TI  - A prospective assessment of quality of life after endoscopic intubation and laser
      therapy for malignant dysphagia.
AB  - BACKGROUND: This study evaluated the effect of endoscopic treatment for malignant
      dysphagia on quality of life (QL) as part of a prospective comparison of Nd:YAG
      laser therapy and intubation. METHODS: Two QL instruments were used: the Quality
      of Life Index (QLI) and a Linear Analogue Self-Assessment (LASA). Only 23 of 43
      patients receiving laser therapy and 15 of 30 having endoscopic intubation agreed
      to partake in QL assessment; serial measurements until death were obtained in 13
      and 9 patients, respectively. RESULTS: Dysphagia grade (DG) as measured on a 5
      point scale, correlated significantly with LASA (n = 92; r = -0.51; P less than
      0.0001) and QLI (n = 92; r = -0.43; P less than 0.0001) scores. In addition,
      there was a strong correlation between LASA and QLI scores (r = 0.678; P less
      than 0.0001). All patients followed up serially until death derived significant
      palliation of their dysphagia with laser treatment and intubation. Such therapy
      resulted in a significant initial improvement in QL, with the mean best LASA and
      QLI scores after treatment being higher than the corresponding mean pretreatment
      scores (P less than 0.004). However, this improvement proved transient; QL
      worsened significantly as a patient's general condition deteriorated during the
      final stages of the illness. The mean last post-treatment LASA and QLI scores in
      both groups (recorded within 5 weeks of death) were less than the corresponding
      mean pretreatment scores (P less than 0.004). CONCLUSIONS: Endoscopic palliation
      of malignant dysphagia results in a significant initial improvement in QL.
      Subsequently, QL worsens appreciably as a patient's general condition
      deteriorates during the terminal phase of disease.

PMID- 1377594
TI  - Periodic acid thiosemicarbazide gelatin methenamine silver (PATSC-GMS) staining
      for transmission electron microscopy.
AB  - A new electron microscopic method is described in which superior staining of
      basement membranes, collagen fibers and glycogen particles in various tissues was
      achieved. This method uses a gelatin methenamine silver solution applied to the
      ultrathin sections on nickel grids after oxidation in a periodic acid. The
      staining results were excellent and tissue components were evenly stained with no
      background silver grains. This method proved to be consistent, reproducible and
      reliable.

PMID- 1377595
TI  - Inhibition of murine tumor growth by an interferon-inducing imidazoquinolinamine.
AB  - The low-molecular-weight imidazoquinolinamine derivative, 1-(2-methylpropyl)-1H
      imidazo[4,5-c]quinolin-4-amine (imiquimod, previously described as R-837),
      induced alpha-interferon (IFN-alpha) in mice. IFN induction was identified at
      oral doses as low as 3 mg/kg. The 10% lethal dose for daily treatment with
      imiquimod was 200 mg/kg. Oral treatment with 30 mg/kg imiquimod once every three
      days significantly inhibited MC-26 colon carcinoma. Delay of treatment from day 1
      to day 5, when tumors were easily palpable, did not reduce benefits. Ten daily
      treatments were slightly more effective than five. However, delivery of the same
      total dose of imiquimod either once every day for 20 days, once every 4 days,
      once every 7 days, or once every 10 days inhibited tumor growth to the same
      level. The antitumor effects of imiquimod were significantly abrogated by an
      antiserum to murine IFN-alpha, suggesting that the antitumor effect was to a
      substantial extent mediated by IFN induction. Imiquimod also significantly
      reduced the number of lung colonies in mice inoculated i.v. with MC-26 tumor
      cells. Combination of treatment with imiquimod and cyclophosphamide was
      significantly (P less than 0.01) better than treatment with either drug alone.
      Combination treatment with cyclophosphamide led to cures in some of the mice
      inoculated either s.c. or i.v. with MC-26 cells. Treatment with imiquimod also
      inhibited the growth of RIF-1 sarcoma and Lewis lung carcinoma but was
      ineffective for P388 leukemia. Imiquimod is an oral IFN-alpha inducer with
      antitumor effectiveness for transplantable murine tumors.

PMID- 1377596
TI  - Expression of human hsp70 in rat fibroblasts enhances cell survival and
      facilitates recovery from translational and transcriptional inhibition following
      heat shock.
AB  - We report here our studies on the inhibitional effect of 45 degrees C heat shock
      on transcriptional and translational activity and their subsequent recovery at 37
      degrees C in Rat-1 cells, thermotolerant Rat-1 cells (TT Rat-1), and Rat-1 cells
      transfected with human hsp70 gene (HR24, M21). Specifically, we ask whether
      overexpression of hsp70 protects cells from heat-induced inhibition in RNA and
      protein synthesis, and/or facilitates cells' ability to recover from
      translational or transcriptional inhibition after heat shock treatment. Our data
      demonstrate that the constitutive expression of human hsp70, by itself, confers
      thermal resistance as expressed in enhanced survival and translational tolerance,
      but not transcriptional tolerance. In addition, the expression of human hsp70 in
      Rat-1 cells facilitates cells' ability to recover from heat-induced inhibition in
      protein and RNA synthesis. After healing at 45 degrees C for 25 min, the time
      required for RNA and protein synthesis to recover is considerably shorter in
      HR24, M21, and TT Rat-1 cells than that in control Rat-1 cells. These results
      provide strong evidence for a direct link between the expression of a functional
      form of mammalian hsp70, and cells' translational tolerance, as well as their
      ability to recover from translational and transcriptional inhibition after heat
      shock.

PMID- 1377597
TI  - Differentiation of HT-29 human colonic adenocarcinoma cells correlates with
      increased expression of mitochondrial RNA: effects of trehalose on cell growth
      and maturation.
AB  - The HT-29 human adenocarcinoma cell line has been used extensively in the study
      of colonic cell differentiation and colon cancer. We report here that
      substitution of glucose with trehalose (alpha-D-glucopyranosyl-alpha-D
      glucopyranoside) depresses growth and promotes mucin-producing, goblet-like
      maturation of HT-29. An initial characterization of this process was made by
      analyzing several cDNA clones whose RNA templates were differentially expressed
      at elevated levels in cells grown in trehalose-containing medium. Seven of the 9
      clones examined corresponded to 6 mitochondrial genes whose expression levels,
      relative to those from glucose-grown cells, ranged from approximately 3-fold for
      16S rRNA to 8-23-fold for NADH dehydrogenase subunit 4. On the other hand, levels
      of mitochondrial DNA copy, measured by using NADH dehydrogenase subunit 4 cDNA as
      probe, were shown to be unaffected by trehalose treatment. Elevation of cellular
      NADH dehydrogenase subunit 4 RNA in HT-29 cultures grown in medium containing
      different components (sodium butyrate, galactose, no-sugar, glucose, cellobiose)
      generally correlated with depressed growth levels and specifically with increased
      numbers of mucin-producing cells present. Like butyrate, the sugar, trehalose, is
      an effective inducer of HT-29 differentiation, and may prove useful as a dietary
      therapeutic, and as a probe for elucidating mitochondrial involvement in colonic
      cell differentiation and transformation.

PMID- 1377598
TI  - Specificity and immunobiological properties of monoclonal antibody IMH2,
      established after immunization with Le(b)/Le(a) glycosphingolipid, a novel
      extended type 1 chain antigen.
AB  - Extended lacto-series type 1 chain antigens lacking type 2 chain core have
      recently been shown to comprise a new type of tumor-associated carbohydrate
      antigen. Examples are Le(a)/Le(a) (IV3Gal beta 1----3[Fuc alpha 1----4]Glc
      NAcLc4Cer) and Le(b)/Le(a) (IV3Fuc alpha 1----2Gal beta 1----3[Fuc alpha 1---
      4]Glc-NAcLc4Cer) (M. R. Stroud, et al., J. Biol. Chem., 266: 8439-8446, 1991;
      Eur. J. Biochem., 203: 577-586, 1992). We have now established an IgG3 mouse
      monoclonal antibody (IMH2) after immunization of mice with Le(b)/Le(a) antigen;
      however, monoclonal antibody (MAb) IMH2 reacted not only with the immunogen used
      but also with Le(y)/Le(x) and to a lesser degree with short-chain Le(y) or Le(b)
      with hexasaccharide ceramide (i.e., IV2FucIII3FucnLc4Cer or IV2FucIII4FucLc4Cer).
      It showed a high incidence of staining and strong reactivity with carcinomas of
      colon, rectum, liver, pancreas, and endometrium, but no reactivity with normal
      colonic mucosa at various loci, and minimal reactivity with normal liver,
      pancreas, or uterine endometrium. On the other hand, it reacted with normal
      gastric mucosa, cecal mucosa, urothelium, adrenal glands, and thymus. Its
      expression in colorectal tumors and normal cecal tissue was independent of
      secretor status, whereas that in normal urothelium was dependent on secretor
      status. MAb IMH2 displayed strong lymphocyte-activated or complement-dependent
      killing of human colonic cancer Colo205 cells in vitro, and inhibition of Colo205
      growth in vivo; this inhibition was comparable to that by MAb NCC-ST-421, which
      is directed to Le(a)/Le(a) epitope (M. Watanabe, et al., Cancer Res., 51:2199,
      1991). These results indicate that a new extended type 1 chain structure,
      Le(b)/Le(a), is a useful tumor marker associated with carcinomas of colon,
      rectum, pancreas, liver, and endometrium and that MAb IMH2 has potential
      diagnostic or therapeutic applicability for these carcinomas.

PMID- 1377599
TI  - 1-beta-D-arabinofuranosylcytosine-diphosphate-choline is formed by the reversal
      of cholinephosphotransferase and not via cytidylyltransferase.
AB  - In an effort to identify the pathway leading to the formation of 1-beta-D
      arabinofuranosylcytosine-diphosphate (ara-CDP)-choline from 1-beta-D
      arabinofuranosylcytosine (ara-C) treatment of cultured cells, as well as of cells
      obtained from leukemia patients, we probed the enzymatic steps involved in the
      CDP-choline pathway for phosphatidylcholine biosynthesis. Ara-C-triphosphate was
      not a substrate for CTP:phosphocholine cytidylyltransferase activity under the
      conditions employed, whereas CTP and dCTP were utilized to form CDP-choline and
      dCDP-choline, respectively. When presented together, ara-C-triphosphate and CTP
      inhibited the enzymatic conversion of CTP to CDP-choline in the presence of
      phosphocholine, with a Ki of 6 mM. Since CTP:phosphocholine cytidylyltransferase
      did not appear to be responsible for the increased levels of ara-CDP-choline, we
      next studied the other enzyme in the pathway for phosphatidylcholine synthesis
      that could form ara-CDP-choline, CDP-choline:1,2-diacylglycerol
      cholinephosphotransferase. CDP-choline:1,2-diacylglycerol
      cholinephosphotransferase activity present in microsomes isolated from L5178Y
      murine leukemia cells exhibited a reversal of its normal catalytic activity,
      using CMP and 1-beta-D-arabinofuranosylcytosine-monophosphate (ara-CMP) along
      with phosphatidylcholine to produce either CDP-choline or ara-CDP-choline, plus
      diradylglycerol. The Vmax and Km values for CMP were 0.78 +/- 0.04 nmol/min/mg
      and 340 +/- 20 microM, respectively, whereas the Vmax and Km for ara-CMP were
      0.22 +/- 0.06 nmol/min/mg and 1410 +/- 540 microM, respectively. A Ki value of 3
      mM was obtained for ara-CMP under the cell-free assay conditions used. These
      results indicate that ara-CDP-choline most likely arises from a reversal of the
      CDP-choline:1,2-diacylglycerol cholinephosphotransferase utilizing ara-CMP,
      rather than from the catalysis of ara-C-triphosphate plus phosphocholine to ara
      CDP-choline by CTP:phosphocholine cytidylyltransferase. It is speculated that
      this mechanism may explain, in part, the rapid cellular lysis observed with high
      dose ara-C therapy.

PMID- 1377600
TI  - Free human chorionic gonadotropin beta subunit in gonadal and nongonadal
      neoplasms.
AB  - The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free
      alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor
      markers for nongonadal malignancies is controversial. In the present report,
      different monoclonal based immunoradiometric assays specific for hCG and its free
      hCG alpha and hCG beta subunits have been used to reevaluate the presence of
      these molecules in the serum of patients with a wide variety of tumors. Serum
      samples from patients with newly diagnosed, persistent, or recurrent malignancies
      of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors
      (n = 309), and nonmalignant disease controls (n = 86) were studied using four
      highly specific and sensitive monoclonal based immunoradiometric assays to hCG
      and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found
      to be common in cancer patients, normal subjects, and disease controls. However,
      serum levels greater than 1000 pg/ml were highly diagnostic of gonadal tumors and
      specifically identified nonseminomatous testicular tumors. Significant serum
      elevations of free hCG alpha subunit (as high as 3000 pg/ml) were found in
      approximately 96% of cancer patients, normal individuals, and disease controls.
      In contrast, free hCG beta subunit levels (greater than or equal to 100 pg/ml)
      were detected in 70 and 50% of patients with nonseminomatous and seminomatous
      testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and
      30% of cervical carcinomas. All normal subjects and disease controls had free hCG
      beta levels less than 100 pg/ml. Thus, the detection of the free hCG beta subunit
      in serum of nonpregnant subjects was highly diagnostic of malignancy in general
      and specifically defines a subgroup of aggressive nongonadal malignancies.

PMID- 1377601
TI  - Intrinsic resistance to methotrexate in human soft tissue sarcoma cell lines.
AB  - A human fibrosarcoma cell line, HT-1080, and four new cell lines (HS-16, HS-28,
      HS-30, and HS-42) were established from untreated patients with mesenchymal
      chondrosarcoma, peripheral nerve sheath sarcoma, malignant hemangiopericytoma,
      and mixed mesodermal tumor, respectively, and were used for analysis of
      mechanisms of intrinsic resistance to methotrexate. All four new cell lines were
      resistant to methotrexate as determined by inhibition of thymidylate synthase in
      whole cells and by growth inhibition, as compared with HT-1080, a methotrexate
      sensitive cell line. Methotrexate uptake, level of dihydrofolate reductase, and
      inhibition of this enzyme by methotrexate in the four cell lines were comparable
      to HT-1080 cells. However, levels of long chain polyglutamates (glu3-5) of
      methotrexate achieved after a 24-h incubation with this drug were much lower in
      the four new cell lines as compared to the HT-1080 cell line (5- to 20-fold
      lower). The low levels of methotrexate polyglutamates formed is likely the major
      cause of intrinsic methotrexate resistance in these new sarcoma cell lines.

PMID- 1377602
TI  - HLA class II antigen expression in human papillomavirus-associated cervical
      cancer.
AB  - The observation that tumor cells of some neoplasms display major
      histocompatibility complex (MHC) class II molecules may be of functional
      significance, influencing the progression of malignancy by allowing the cancer
      cells to present antigen to the immune system. In the normal cervix, class II
      molecules are expressed by columnar but not squamous epithelium. The pattern of
      MHC class II expression in cervical carcinomas has been documented using
      immunohistochemical methods. Of 53 cervical squamous carcinomas examined for MHC
      class II expression, only 17% maintained a negative phenotype characteristic of
      the epithelium from which they were derived, while the remaining tumors exhibited
      either uniform (45%) or heterogeneous (38%) expression. Tumor areas which were
      class II positive also express class II associated invariant chain and the
      adhesion molecules lymphocyte function antigen 3 and intercellular adhesion
      molecule 1. The DR, DP, and DQ class II MHC subloci are differentially expressed,
      suggesting independent regulation. There is a trend for tumors with the uniform
      class II phenotype to predominantly express DR antigen, whereas tumors of the
      heterogeneous class II phenotype express with equal frequency either DR or DP
      antigens dominantly. There is no apparent influence of class II status on
      lymphocyte infiltration of the tumors. The presence of human papillomavirus 16
      DNA in the cervical carcinoma specimens was analyzed by Southern blotting of
      restriction enzyme digested DNA and no correlation between the presence of human
      papilloma virus and MHC class II expression was found.

PMID- 1377603
TI  - Distribution patterns and coexistence of neurohormonal peptides (ANP, BNP, NPY,
      SP, CGRP, enkephalins) in chromaffin cells and nerve fibers of the anuran adrenal
      organ.
AB  - Immunohistochemical techniques were used to study the adrenal organs of the
      anuran species Rana esculenta, Caldula pulchra and Bufo marinus with respect to
      the distribution and coexistence of atrial natriuretic peptide (ANP), brain
      natriuretic peptide (BNP), substance P (SP), calcitonin gene-related peptide
      (CGRP), neuropeptide Y (NPY), Leu-enkephalin (Leu-ENK). Met-enkephalin-Arg-Phe
      (MEAP) and dynorphin A 1-17 (DYN). Antisera against enzymes involved in
      catecholamine synthesis, i.e., dopamine-beta-hydroxylase (DBH) and tyrosine
      hydroxylase (TH), were used for the identification of chromaffin cells. ANP
      immunoreactive (-IR) cells occurred in high densities (30%-70% of the total cell
      population) in all species investigated. In C. pulchra and B. marinus, BNP-IR
      cells constituted a population of non-DBH-IR and non-TH-IR cells that were
      different from the ANP-IR cells. A large proportion of the adrenal cells (10%
      55%) were immunoreactive to Leu-ENK, and a minority (2%-5%) showed MEAP
      immunoreactivity. DYN-immunoreactivity was not observed. The anurans studied
      exhibited small numbers of SP-IR, CGRP-IR and NPY-IR cells. Immunoreactivities
      for ANP + Leu-ENK and Leu-ENK + MEAP were shown to coexist. In C. pulchra and B.
      marinus, immunoreactions for ANP + NPY, ANP+SP and SP + CGRP were also
      colocalized. Except for DYN, all neurohormonal peptides also occurred in intra
      adrenal nerve fibers. SP-IR fibers also displayed CGRP-immunoreactivity and some
      Leu-ENK-IR fibers contained MEAP-immunoreactivity. In C. pulchra, NPY-IR fibers
      were found that also showed ANP-immunoreactivity.

PMID- 1377604
TI  - Immunohistochemical localization of serotonin, leu-enkephalin, tyrosine
      hydroxylase, and substance P within the visceral sensory area of cartilaginous
      fish.
AB  - We examined the distribution of immunoreactivity to serotonin (5-HT), leu
      enkephalin (LENK), tyrosine-hydroxylase (TH), and substance P (SP) within the
      primary visceral sensory region of cartilaginous fish. Two genera of sharks,
      Squalus and Heterodontus, a skate, Raja, a ray, Myliobatis, and a holocephalian,
      Hydrolagus, were used. Cranial nerves, VII, IX, and X enter the visceral sensory
      complex from the lateral aspect and divide it into lobes. Based on sagittally cut
      sections, there are four lobes in Hydrolagus and five in Squalus, corresponding
      to the number of gill arches. The neurochemicals are differentially distributed
      within each lobe. LENK+ and 5-HT+ fibers are located in all regions within the
      visceral sensory complex. SP+ fibers are extremely dense in a dorsolateral
      subdivision and do not extend as far ventrally as 5-HT+ and LENK+ fibers. The
      lobes lack 5-HT+ cells, but contain a few LENK+ and SP+ cells. Many TH+ cells are
      distributed in dorsomedial portions of the complex, but there are few TH+ fibers.
      Thus, the visceral sensory area of cartilaginous fish contains several divisions
      that can be distinguished by their neurochemical content.

PMID- 1377605
TI  - Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis.
AB  - Mammalian myogenesis is biphasic: primary myoblasts fuse to form primary
      myotubes, then secondary myoblasts align along the primary myotubes and form
      secondary myotubes, which comprise most of adult muscle. We provide evidence that
      an integrin (VLA-4) and its counter receptor (VCAM-1) have a role in secondary
      myogenesis. Both receptors are synthesized by cultured muscle cells: VLA-4 is
      induced as myotubes form, whereas VCAM-1 is present on myoblasts and myotubes. In
      vivo, both molecules are expressed at sites of secondary myogenesis, VLA-4 on
      primary and secondary myotubes, and VCAM-1 on secondary myoblasts and on regions
      of secondary myotubes apposed to primary myotubes. These patterns suggest that
      VLA-4-VCAM-1 interactions influence alignment of secondary myoblasts along
      primary myotubes and/or the fusion of secondary myoblasts. In support of the
      latter possibility, antibodies to VLA-4 or VCAM-1 inhibit myotube formation in
      culture.

PMID- 1377607
TI  - [Comparison of ultrastructural and immunohistochemical studies on renal cell
      carcinoma and human embryo kidney].
AB  - 26 cases of renal cell carcinoma (RCC) were studied by both light microscopy and
      electron microscopy, accompanied with 9 cases of human embryo kidney as control.
      20 cases of RCC in different degree of cell differentiation, 4 cases of human
      embryo kidney and 1 case of adult human kidney were studied with
      immunohistochemical methods. The results indicated that the histostructures and
      antigen expression of RCC were rather complicated and the ultrastructures and
      antigen expression changes of RCC seemed very similar to those of the developing
      embryonic kidneys. This indicated, that RCC might have originated from
      nephroblastoma cells.

PMID- 1377606
TI  - Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling
      by the 70 kd S6 protein kinases.
AB  - The macrolide rapamycin blocks cell cycle progression in yeast and various animal
      cells by an unknown mechanism. We demonstrate that rapamycin blocks the
      phosphorylation and activation of the 70 kd S6 protein kinases (pp70S6K) in a
      variety of animal cells. The structurally related drug FK506 had no effect on
      pp70S6K activation but at high concentrations reversed the rapamycin-induced
      block, confirming the requirement for the rapamycin and FK506 receptor, FKBP.
      Rapamycin also interfered with signaling by these S6 kinases, blocking serum
      stimulated S6 phosphorylation and delaying entry of Swiss 3T3 cells into S phase.
      Neither rapamycin nor FK506 blocked activation of a distinct family of S6 kinases
      (RSKs) or the MAP kinases. These studies identify a rapamycin-sensitive signaling
      pathway, argue for a ubiquitous role for FKBPs in signal transduction, indicate
      that FK506-FKBP-calcineurin complexes do not interfere with pp70S6K signaling,
      and show that in fibroblasts pp70S6K, not RSK, is the physiological S6 kinase.

PMID- 1377608
TI  - [The changes of substance P contents in central nervous system of renal
      hypertensive rats].
AB  - The changes of substance P-like immunoreactivity (SPLI) were determined in the
      central nervous system of renal hypertensive rats (produced by application of a
      constricting clip on the left renal artery), as compared with those of sham
      operated controls. The results showed that the substance SP (SP) contents in the
      rostral ventrolateral medulla (RVM) and intermediolateral cell column (IML) of
      the thoracic spinal cord in renal hypertensive rats (RHR) were significantly
      higher than those in the control group. On the other hand, there was no
      significant difference of SP content in the hypothalamus (HP) between RHR and
      control groups. Intrathecal injection of SP antagonist lowered the mean blood
      pressure in both RHR and control groups. This data suggests that the excess SP
      contents in RVM and IML may be closely related to the pathogenesis of
      hypertension.

PMID- 1377609
TI  - [Effect of hypoxia on vasodilation induced by substance P (SP) and calcitonin
      gene-related peptide (CGRP)].
AB  - In this paper, isolated rabbit arteries (renal artery, RA; femoral artery, FA;
      basilar artery, BA) were used to study the effect of hypoxia on vasodilation
      induced by substance P (SP) and calcitonin gene-related peptide (CGRP). The
      results showed that hypoxia caused a marked decrease of the arteries, response to
      SP (10(-7) mol/L) and CGRP (2.8 x 10(-9) mol/L). Repeated hypoxia even resulted
      in a complete disappearance of response. On the second hypoxia, CGRP (2.8 x 10(
      9) mol/L) induced vasodilation on BA was vanished. On the third hypoxia,
      vasodilation induced by CGRP (2.8 x 10(-9) mol/L) on FA and that induced by SP (2
      x 10(-7) mol/L) on BA were vanished, and CGRP (2.8 x 10(-9) mol/L) induced a
      lesser extent of vasodilation on RA. At the fourth time, SP (10(-7) mol/L) 
      induced vasodilation of FA disappeared, and that on RA was small. At the fifth
      time, the effect of SP (10(-7) mol/L) on RA was nearly vanished. It is concluded
      that the effect of hypoxia on CGRP-induced vasodilation is stronger than that on
      SP-induced vasodilation, and the effect is most pronounced on the BA.

PMID- 1377610
TI  - [Effects of substance P in rat spinal cord on the humoral immune response to
      SRBC].
AB  - The effects of substance P (SP) in rat spinal cord on the humoral immune response
      to sheep red blood cells (SRBC) were investigated by the hemolytic plaque-forming
      cell (PFC) technique. Radioimmunoassay was used for assessing SP content.
      Catecholamines contents were measured by high performance liquid chromatography
      (HPLC) with electrochemical-detection. The results suggest that SP in the spinal
      dorsal horn, but not in the lateral horn, could inhibit the thymus-dependent
      humoral immune response to SRBC, and this inhibitory effect might be related to
      the influence of dorsal horn SP on thymic activity. Increased SP content in the
      spinal dorsal horn at the peak of a humoral immune response might suppress the
      immune response and play a negative feedback role, preventing excessive immune
      response.

PMID- 1377612
TI  - Expression of the angiotensinogen gene and localization of its protein in the
      human heart.
AB  - BACKGROUND: There have been no reports on the presence of the tissue renin
      angiotensin system in the human heart, although the presence of angiotensinogen
      has been described in the animal heart. METHODS AND RESULTS: To determine whether
      angiotensinogen is synthesized in the human heart, we examined angiotensinogen
      messenger RNA (mRNA) synthesis in autopsy hearts by using ribonuclease protection
      assay. As a result, angiotensinogen mRNA was detected in the atrial muscle,
      muscles of the conduction system, and the left ventricular wall. In the left
      ventricular wall, mRNA expression was more prominent in the subendocardial
      muscles than in the midcardial or epicardial muscles. Using a monoclonal antibody
      to human angiotensinogen in immunoblotting experiments, we detected two closely
      spaced bands at approximately 70 kd in the heart, which was quite consistent with
      the human angiotensinogen molecule. Immunohistochemical studies with this
      monoclonal antibody demonstrated intense immunoreactivity in the atrial muscles,
      the muscles of the conduction system, and those of the subendocardial layers.
      CONCLUSIONS: We conclude that angiotensinogen was synthesized in the human heart.
      It was evident that the localization of angiotensinogen was not ubiquitous in the
      cardiac muscles, showing its predilection for the atrial muscles, muscles of the
      conduction system, and subendocardial layer of the left ventricle.

PMID- 1377611
TI  - [Protective effect of 764-3 on experimental inflammation].
AB  - The antiinflammatory effect of 764-3 was investigated in rat models of lung
      inflammation and pleurisy induced by bleomycin intratracheal instillation and
      carrageenan intrapleural cavity injection respectively. 4 mg/100 g BW.d 764-3
      hypodermal injection significantly inhibited the lung inflammatory changes in
      bleomycin treated rats. Compared with the experimental group, lung index,
      histamine content in lung tissue and in bronchoalveolar lavage fluid (BALF),
      number of PMN in BALF and BALF beta-glucuronidase activity significantly deceased
      in the therapeutic rats. 8 mg/100 g BW 764-3 intramuscular injection
      significantly inhibited the volume, number of PMN, protein content and beta
      glucuronidase activity increase in carrageenan-induced pleural exudate fluid. The
      antiinflammatory effect of 8 mg/100 g BW 764-3 was equal to that of 3 mg/100 g BW
      hydrocortisone. 4 mg/100 g BW 764-3 injection significantly inhibited the
      increases in PMN numbers and beta-glucuronidase activity in pleural exudate
      fluid. 2 mg/100 g BW 764-3 injection significantly inhibited the PMN increase in
      pleural exudate fluid only. 1 mg/100 g BW 764-3 injection showed no
      antiinflammatory effect. When 764-3 was administered orally, the antiinflammatory
      effect was unsatisfactory. 5 mg/100 mg BW 764-3 significantly inhibited the
      volume, number of PMN, protein content and beta-glucuronidase activity of
      carrageenan-induced pleural exudate fluid. 2.5 mg/100 g BW 764-3 significantly
      inhibited the volume and protein content increases in pleural exudate fluid. But
      3.5 mg/100 g BW 764-3 showed no antiinflammatory effect. The authors indicate
      that the antiinflammatory effect of orally administered 764-3 was not stable.

PMID- 1377613
TI  - Cardiac risk of speed traps.
AB  - Twenty-two patients with stable cardiac disease drove into a radar trap while
      having an ambulatory electrocardiogram. All patients reported cardiac symptoms,
      heart rate increases, and appearance of repetitive ventricular arrhythmias.
      Myocardial ischemia was observed in some patients. Being caught while car
      speeding under the stresses of daily life may induce potentially dangerous
      cardiac effects. The data confirm the effects of stress and adrenergic tone on
      ventricular arrhythmias.

PMID- 1377615
TI  - Alkaline phosphatase in the lactating bovine mammary gland and the milk fat
      globule membrane. Release by phosphatidylinositol-specific phospholipase C.
AB  - 1. Alkaline phosphatase is covalently bound to bovine mammary microsomal
      membranes and milk fat globule membranes through linkage to phosphatidylinositol
      as demonstrated by the release of alkaline phosphatase following treatment with
      phosphatidylinositol-specific phospholipase C. 2. The release of alkaline
      phosphatase from the pellet to the supernatant was demonstrated by enzyme assays
      and electrophoresis. 3. Electrophoresis of the solubilized enzymes showed that
      the alkaline phosphatase of the microsomal membranes contained several isozymes,
      while only one band with alkaline phosphatase activity was seen in the fat
      globule membrane. 4. Levamisole and homoarginine were potent inhibitors of the
      alkaline phosphatase activities in both membrane preparations and in bovine liver
      alkaline phosphatase, but not in calf intestinal alkaline phosphatase.

PMID- 1377616
TI  - Determination of the molecular weights of ribonuclease isozymes in a cell-free
      crude extract of Dictyostelium discoideum, by activity-staining of gels after SDS
      PAGE.
AB  - 1. In a previous report we described three isozymes of intracellular ribonuclease
      in Dictyostelium discoideum, which were found in vegetative cells. Here we report
      that the molecular weights of the three isozymes from vegetative cells. 2. They
      are 14.3 kDa, 60 kDa and 80 kDa, as determined by activity-staining of gels after
      SDS-PAGE. 3. For renaturation of ribonucleolytic activity from D. discoideum
      cells after SDS-PAGE, fibrinogen-containing gels were used and gels were washed
      in aqueous isopropanol to remove detergent. Results of studies by this method
      suggest that each of these isozymes is composed of only a single polypeptide. 4.
      The effect of the buffer system on this technique is discussed.

PMID- 1377614
TI  - Substrate adhesiveness and experimental metastatic potential of rat ascites
      hepatoma AH7974-derived variant sublines.
AB  - Cells of an adherent subline (74AD, adhesion greater than 95%) and a floating
      subline (74FL, adhesion less than 1%) of rat ascites hepatoma AH7974 produced
      substrates containing fibronectin (FN), laminin (LN) and type IV collagen (CL
      IV), with 74AD cells producing higher levels of each component. 74AD cells
      possessed high adhesion affinities to LN and CL-IV substrates. By contrast, 74FL
      cells hardly adhered to these purified attachment proteins. The difference in
      adhesion between the two lines in vitro tended to increase on incubation of the
      cells in medium containing fetal bovine serum. However, 74FL and 74AD cells
      adhered avidly to the extracellular matrix (ECM) of vascular endothelial cells.
      Although the cell-ECM adhesion apparently was not inhibited by pretreatment of
      the ECM with anti-FN, anti-LN and anti-CL-IV antibodies, the 74FL cell-ECM
      adhesion was inhibited considerably by pretreatment of the ECM with a mixture of
      these antibodies, especially with a combination of anti-FN and anti-LN
      antibodies. The lung-colonizing potential of 74FL cells was greater than that of
      74AD cells, but the liver-colonizing potential of 74FL cells was less than that
      of 74AD cells. These results suggest that rat ascites hepatoma cells with
      extremely reduced substrate adhesiveness retain an adhesion mechanism that binds
      to FN and LN in the ECM of vascular endothelial cells. This mechanism may be a
      minimum essential unit of tumor cell-ECM adhesion in lung colonization, but the
      unit is insufficient for liver colonization of these cells.

PMID- 1377617
TI  - A comparative study of covalently-bound fatty acids in keratinized tissues.
AB  - 1. Covalently-bound fatty acids were characterized in keratinous tissues obtained
      from a wide range of animals. 2. 18-Methyleicosanoic acid was a major component
      in all the mammalian fur samples examined except monotreme fur. In monotreme fur
      26-carbon fatty acids predominated. 3. Fatty acids from feather keratin and
      reptile skin had different profiles to the alpha-keratins of mammalian fur. 4.
      The major forms of covalently-bound fatty acids are very similar in species that
      diverged up to 125 million years ago.

PMID- 1377618
TI  - The effect of exogenous insulin-like growth factor-I (IGF-I) on the reproductive
      performance of female rats, and on serum concentrations of endogenous IGF-I and
      IGF-I binding proteins.
AB  - The effect of exogenous IGF-I on the reproductive performance of female rats was
      examined by infusing either recombinant human IGF-I (400 micrograms/d; n = 19) or
      vehicle (n = 18) over a four-day period (the time of one reproductive cycle)
      beginning on the day following estrus. The females were exposed to male rats one
      day after the infusions had commenced, and were euthanized 15 d later. There was
      no treatment effect on serum progesterone levels at this time or on the number of
      fetuses. Furthermore, the number of corpora lutea were not different between the
      IGF-I and vehicle infused groups (15.8 vs. 14.8; P = 0.09). Total serum IGF-I
      concentrations, as determined with a polyclonal antiserum based RIA, were
      increased approximately three-fold in samples obtained 20 hr after commencing the
      IGF-I infusion. These samples were also analyzed for IGF-I with a monoclonal
      antibody based RIA previously shown to detect human, but not rat, IGF-I. By
      subtraction, the concentration of endogenous rat IGF-I was found to be
      approximately 60% higher in IGF-I-infused rats than in control rats. This
      increase was likely due to a reduced clearance rate of IGF-I from the
      circulation, caused by a marked induction of 42-46 kDa and 30-34 kDa IGF-I
      binding proteins observed in these samples with a ligand blot technique. The
      binding protein induction indicates that the infused IGF-I was bioactive. This
      induction may have attenuated the effects of IGF-I on ovarian function.

PMID- 1377619
TI  - [Balloon dilatation for prostatic obstruction].
AB  - Balloon catheter dilatation of the prostate (BCDP) was performed in 25 patients
      with prostatic hypertrophy. All patients suffered from dysuria or urinary
      retention. Follow-up for 8-14 months showed that 20 patients had satisfactory
      results. The balloon catheter of 25 mm x 50 mm was inflated at 4-6 atm for 10-15
      minutes. BCDP was modified for the use in the local hospitals.

PMID- 1377621
TI  - [Determination of antigen-dependent activity of human lung cancer transfer factor
      by H3-leucine leucine leukocyte adherence inhibition assay].
AB  - This report is to demonstrate the antigen-dependent activity of human lung cancer
      transfer factor (Sp-TF). Sp-TFM was prepared from spleen of mice immunized with
      the human lung cancer cell line A549. [3H]-leu leukocyte adherence inhibition
      assay ([3H]-leu-LAI) was modified to identify activity of Sp-TFM. Leukocytes
      obtained from non-immunized mice were divided into eight groups as follows: 1.
      Control without TF or antigen; 2. Sp-TFM and antigen of cell line A549 (A549 Ag);
      3. Sp-TFM alone; 4. Sp-TFM and ascitic tumor cell H22 antigen of mice (H22Ag); 5.
      Sp-TFM and antigen of human gastric cancer cell (HGCCAg); 6. Sp-TFM and antigen
      of human normal lung tissue (NLTAg); 7. Nor special TF of mice (N-TFM) and
      A549Ag; 8. A549Ag alone. When normal leukocytes were incubated with Sp-TFM and
      A549 antigen, the leukocytes adherence inhibition index (LAII) was significantly
      higher than those of the other groups. The different LAII of Sp-TFM to A549Ag and
      other experimental groups were highly significant (P less than 0.001). The
      results demonstrated that Sp-TFM could transfer specific cell mediated immunity
      to non-immune leukocytes. The TF prepared from spleen of goat immunized with
      antigen from lung cancer of patients (Sp-TFG) showed antigen specific activity as
      well as Sp-TFM.

PMID- 1377622
TI  - [Agyrophilic nucleolar organizer region counts as related to bromodeoxyuridine
      incorporation scores in ovarian clear cell carcinoma cells].
AB  - The value of agyrophilic nucleolar organizer region (AgNOR) stain as potential
      technique for the estimation of cell kinetics was assessed in this study. The
      daily AgNOR counts and the scores of the proliferation-associated marker
      bromodeoxyuridine (BrdU) in a human ovarian carcinoma cell line-OCC1 for 10 days
      after subculture were determined. The correlation between AgNOR counts and BrdU
      incorporation scores was highly significant (r = 0.86, P less than 0.01).
      Therefore AgNOR counts offer a potential tool to provide cytokinetic information.

PMID- 1377620
TI  - Weight loss induced by gastric implant in rats. Effects of capsaicin sensory
      denervation.
AB  - To study the efficacy and mechanism of action of the intragastric bubble, 1- to 5
      ml silicone bubbles were surgically implanted into the stomachs of 10- to 12-week
      old female rats. To test the hypothesis that the satiety effects of the implant
      are mediated by visceral sensory nerves, a subgroup was treated as neonates with
      the sensory neurotoxin capsaicin, 50 mg/kg subcutaneously. In control animals,
      the implants caused a transient decrease in body weight, compared to sham
      implanted animals, most evident at three days and abolished by 18 days after
      operation. In contrast, capsaicin-treated animals did not lose weight in response
      to gastric implantation. Substance P was decreased in the vagus nerves of
      capsaicin-treated animals, confirming sensory denervation. At autopsy, all
      gastric implanted rats had enlarged stomachs. We conclude that intact sensory
      innervation is essential for weight loss in response to the gastric bubble.

PMID- 1377623
TI  - Evidence for a highly selective RNA transport system and its role in establishing
      the dorsoventral axis of the Drosophila egg.
AB  - The specification of cell fates along the dorsoventral axis of the Drosophila
      embryo is dependent on the asymmetric distribution of proteins within the egg and
      within the egg's outer membranes. Such asymmetries arise during oogenesis and are
      dependent on multiple cell-cell interactions between the developing oocyte and
      its neighboring somatic follicle cells. The earliest known such interaction
      involves the generation of a signal in the oocyte and its reception in the
      follicle cells lying on the dorsal surface of the oocyte at approximately stage
      10 of oogenesis. Several independent lines of investigation indicate that the
      fs(1)K10 (K10) gene negatively regulates the synthesis of the signal in the
      oocyte nucleus. Here we present data that indicate that the accumulation of K10
      protein in the oocyte nucleus is a multistep process involving: (1) the synthesis
      of K10 RNA in nurse cells, (2) the rapid transport of K10 RNA from nurse cells
      into the oocyte, (3) the localization of K10 RNA to the anterior margin of the
      oocyte, and (4) K10 protein synthesis and localization. K10 RNA is transported
      into the oocyte continuously beginning at approximately stage 2. This indicates a
      high degree of selectivity in transport, since most RNAs synthesized in stage 2
      and older nurse cells are stored there until stage 11, when nurse cells donate
      their entire cytoplasm to the oocyte. The sequences responsible for the early
      (pre-stage 11) and selective transport of K10 RNA into the oocyte map to the 3'
      transcribed non-translated region of the gene. None of the other identified genes
      involved in dorsoventral axis formation are required for K10 RNA
      transport.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377624
TI  - Retinal fate and ganglion cell differentiation are potentiated by acidic FGF in
      an in vitro assay of early retinal development.
AB  - One of the earliest events in vertebrate eye development is the establishment of
      the pigmented epithelium and neural retina. These fundamentally different tissues
      derive from the invaginated optic vesicle, or optic cup. Even after achieving a
      fairly advanced state of differentiation, the pigmented epithelium exhibits the
      same potential as the optic cup in that it can "transdifferentiate" into neural
      retina. C. M. Park and M. J. Hollenberg (Dev. Biol. 134, 201-205, 1989)
      discovered that administration of basic fibroblast growth factor, coupled with
      retinal removal, could trigger this transformation in vivo. We have developed a
      quantitative in vitro assay to study the role(s) of the fibroblast growth factor
      (FGF) family in this phenomenon and more generally in early retinal development.
      We found that several aspects of the process, including inhibition of pigmented
      epithelium differentiation, proliferation, and conversion to a retinal fate, were
      not strictly correlated. Both acidic and basic FGFs were found to potentiate all
      aspects of the process, with acidic FGF being 4 to 20 times more potent than
      basic FGF for inhibition of pigmentation and induction of retinal antigens.
      Depending upon its concentration, acidic FGF induced from 40% to 80% of the cells
      in the explants to produce antigens normally expressed by retinal ganglion cells,
      the first cell type to be generated in retinal development. Expression of such a
      ganglion cell marker could be directly stimulated in non-dividing cells as well
      as in dividing cells, indicating that conversion from the pigmented epithelial to
      retinal fate did not require cell division. These data suggest that acidic FGF,
      or a related molecule, may function in establishment of retinal fate from the
      optic cup. This effect may be directly or indirectly mediated by induction of
      retinal ganglion cell fate among multipotent progenitor cells.

PMID- 1377625
TI  - Effects of W (c-kit) gene mutation on gametogenesis in male mice: agametic
      tubular segments in Wf/Wf testes.
AB  - Mutations of the W (c-kit) gene, which encodes a transmembrane tyrosine kinase
      receptor, affect the development and differentiation of many types of stem cell.
      Most homozygous W mutant mice are sterile, due to a lack of germ cells arising
      during embryonic development, but one of the notable exceptions is Wf/Wf mice,
      which are fully fertile in both sexes. In order to elucidate the effects of the
      Wf mutation on spermatogenesis, postnatal spermatogenesis in Wf/Wf mice was
      histologically examined. The number of gonocytes at birth was significantly
      reduced and small portions of agametic seminiferous tubule segments were observed
      in mutant mice. It is suggested that this is due to a deficiency of primordial
      germ cells (PGC). Other than the agametic tubules, there was no evidence of
      reduced spermatogenesis after birth. These results indicate that the function of
      the W (c-kit) gene is more necessary for the development of PGC than for
      postnatal germ cells.

PMID- 1377626
TI  - The role of second look laparotomy and tumor markers in the follow-up of
      endodermal sinus tumor of the ovary. A case report and review of the literature.
AB  - Endodermal sinus tumor (EST) of the ovary is extremely rare and little
      information exists about therapy and the role of second-look laparotomy in the
      management of this entity. A case of EST of the ovary in a 21 year old woman is
      reported. She received conservative surgery and six courses of combination
      therapy consisting of Vincristine, Actinomycin D and Cyclophosphamide before
      second-look laparotomy. Due to progression of the disease second-line
      polychemotherapy with Vinblastine, Bleomycin and Cisplatin was administered. This
      new regimen reduced the alpha-fetoprotein to normal levels although the patient
      was not free of disease on second-look laparotomy. Precise guidelines for the
      management of this disease, especially in advanced stages, are still lacking.

PMID- 1377627
TI  - Possible mechanism of ruthenium red antagonism of capsaicin-induced action in the
      isolated guinea pig ileum.
AB  - Ruthenium red (3-5 microM) antagonism of the inhibitory effect of capsaicin (1
      microM) on the contractile response to mesenteric nerve stimulation in the
      presence of hexamethonium (50 microM) and guanethidine (2 microM) was reversed
      significantly by sialic acid (2 mM) or neuraminidase (0.1 U/ml). These results
      suggested that ruthenium red at low concentrations inhibits the capsaicin-induced
      desensitization of activated Ca2+ influx into sensory nerves at least in part by
      binding to sialic acid residues.

PMID- 1377628
TI  - Affinity profiles of pizotifen, ketotifen and other tricyclic antimuscarinics at
      muscarinic receptor subtypes M1, M2 and M3.
AB  - The affinity of pizotifen, ketotifen and other tricyclic antimuscarinic drugs for
      different muscarinic receptor subtypes was investigated in vitro in functional
      experiments with field-stimulated vas deferens of the rabbit (M1 and M2
      receptors) and with ileum and trachea of the guinea-pig (M3 receptors). All
      compounds were competitive antagonists in the three tissues. Like the close
      analogue cyproheptadine (pA2 = 7.99-8.08), pizotifen (pA2 = 7.23-7.81) and
      ketotifen (pA2 = 6.34-6.99) were devoid of selectivity for the receptor subtypes
      studied. Thiazinamium, although exhibiting high affinity for muscarinic receptors
      (pA2 = 7.83-8.51), was found to be non-selective. In contrast, the novel
      pirenzepine analogue nuvenzepine was selective for M1 receptors (pA2 = 6.63
      7.74). The lack of selectivity of cyproheptadine, pizotifen and ketotifen is
      reflected in the chemical structures of these drugs. All three antagonists are
      composed of a very similar tricyclic ring system linked to a 1-methyl-4
      piperidylene ring. The finding that thiazinamium, pizotifen and cyproheptadine
      were potent muscarinic antagonists and possessed non-selective affinity
      characteristics may have therapeutic implications.

PMID- 1377629
TI  - Modulation of hypothalamic norepinephrine release by atrial natriuretic peptide:
      involvement of cyclic GMP.
AB  - The ability of atrial natriuretic peptide (ANP) to modulate K+-stimulated release
      of [3H]norepinephrine ([3H]NE) from rat hypothalamic slices was investigated. ANP
      (1-28) significantly decreased K+-stimulated [3H]NE release in a concentration
      dependent manner (maximal inhibition = 22% of control with 100 nM, ED50 = 70 pM).
      Pretreatment with pertussis toxin did not alter the response to ANP. 8Br-cGMP (10
      microM), a cGMP analog, significantly decreased [3H]NE release and when combined
      with 10 nM ANP-(1-28), an additive effect was observed. Additionally, 3-isobutyl
      1-methylxanthine (IBMX) (200 microM), a phosphodiesterase inhibitor, combined
      with ANP-(1-28) 10 nM, significantly decreased [3H]NE release. These results
      indicate that ANP-(1-28) modulated release of [3H]NE from rat hypothalamic slices
      and the effect is most likely mediated by elevation of intraneuronal cGMP.

PMID- 1377630
TI  - Effect of interleukin-1 receptor antagonist on antigen-induced pulmonary
      responses in guinea pigs.
AB  - The ability of the human interleukin-1 receptor antagonist, IL-1ra, to inhibit
      aerosolized antigen-induced airway hyperreactivity to i.v. substance P and
      bronchoalveolar lavage inflammatory cell accumulation, under in vivo conditions,
      was assessed in guinea pigs. Pretreatment with IL-1ra (30 mg/kg i.p.,
      administered 30 min prior to antigen challenge) inhibited increases in
      bronchoalveolar lavage fluid neutrophil accumulation at 1 h following aerosolized
      antigen (0.1% ovalbumin for 30 min) exposure. IL-1ra (30 mg/kg i.p., administered
      30 min pre-antigen and 3 h post-antigen) also significantly attenuated antigen
      induced increases in bronchoalveolar lavage fluid leukocytes at 6 h following
      antigen. However, IL-1ra (30 mg/kg i.p., administered 30 min pre-antigen as well
      as 6 and 12 h post-antigen) did not affect antigen-induced bronchoalveolar lavage
      fluid leukocyte accumulation at 24 h following antigen. A limited, but
      significant (P less than 0.05), reduction in antigen-induced airway
      hyperreactivity to 10 micrograms/kg, but not lower doses, of i.v. substance P
      (measured as peak increases in lung resistance in cm H2O/ml per s) at 6 h
      following antigen was noted in the presence of IL-1ra (30 mg/kg i.p.). In
      conclusion, IL-1ra inhibited antigen-induced airway hyperreactivity to i.v.
      substance P and bronchoalveolar lavage fluid inflammatory leukocyte influx in the
      guinea pig, in a time-dependent manner, suggesting that cytokines, such as IL-1,
      may contribute to the pathophysiology surrounding this pulmonary anaphylaxis
      model.

PMID- 1377631
TI  - Effect of gepirone on increases in tryptophan hydroxylase in response to sound
      stress.
AB  - Pretreatment (15 min) of male rats with gepirone given parenterally (10 mg/kg
      i.p.) or intracranially into the dorsal raphe nucleus (14 or 21 micrograms)
      blocks the rapidly reversible increase in brain tryptophan hydroxylase activity
      and 5-hydroxyindolamine acetic acid tissue levels seen in vitro after 1-h acute
      sound stress. Chronic gepirone treatment over 28 days (40 mg/day s.c.) prevents
      the stable enzyme activity increase induced by repeated sessions of sound stress,
      and the rapidly reversible increase always observed following sound stress. The
      gepirone metabolite, 1-(2-pyrimidinyl)-1-piperazine, is inactive in each of these
      experiments. Transient blood pressure elevations occur with each sound
      presentation, but no persistent hypertension is observed with repeated sound
      stress exposures. Gepirone may block the sound stress-induced biochemical
      increases by its inhibition of serotonergic neuronal firing in the dorsal raphe
      nucleus that is mediated by its agonist action at the somatodendritic (5-HT1A)
      autoreceptors.

PMID- 1377632
TI  - Substance P depresses bioelectrical responses evoked in the nucleus tractus
      solitarii: interaction with gamma-aminobutyric acid-ergic neurons.
AB  - The effects of intracerebroventricular (i.c.v.) administration of substance P
      (SP) and gamma-aminobutyric acid (GABA) on responses evoked in the nucleus
      tractus solitarii (NTS) by electrical stimulation of the ipsilateral sinusal
      nerve were studied in alpha-chloralose-anesthetized rats. Both SP (0.01-10
      micrograms) and GABA (100 micrograms) significantly depressed the presumably C
      fiber mediated, late negative wave of the response. The effects were almost
      completely prevented by bicuculline (10 micrograms i.c.v.). It is concluded that
      i.c.v. administered SP induces dose-dependent depression of baro- and/or
      chemosensory transmission in the NTS, via a mechanism involving interactions with
      GABAergic neurons of the NTS.

PMID- 1377633
TI  - Nitric oxide synthase inhibitors cause sustained, but reversible, hypertension
      and hindquarters vasoconstriction in Brattleboro rats.
AB  - Homozygous male Brattleboro rats were given a solution of NG-monomethyl-L
      arginine (L-NMMA; 1 mg ml-1) to drink for a period of 7 days. There was a
      persistent elevation of mean arterial blood pressure, accompanied by a
      significant hindquarters vasoconstriction. Within 9 h of withdrawal of L-NMMA all
      variables were not different from pre-L-NMMA values. Brattleboro rats (n = 3)
      which had been drinking NG-nitro-L-arginine methyl ester (L-NAME) solution (0.05
      mg ml-1) for 5-6 months showed an increased blood pressure which reversed to
      normal within 48 h after withdrawing the L-NAME. Thus, inhibition of nitric oxide
      synthesis leads to long-lasting, but reversible, hypertension.

PMID- 1377634
TI  - Stability of septohippocampal neurons following excitotoxic lesions of the rat
      hippocampus.
AB  - The present study examined the effects of removing hippocampal nerve growth
      factor (NGF)-producing neurons upon cholinergic and noncholinergic
      septohippocampal projecting neurons. To deplete septal/diagonal band neurons of
      their intrinsic source of NGF, rats received unilateral intrahippocampal
      injections of ibotenic acid and were sacrificed 2-24 weeks later. Choline
      acetyltransferase and parvalbumin immunohistochemistry failed to reveal changes
      in the number of cholinergic or gamma-aminobutyric acid-containing neurons,
      respectively, within the septal/diagonal band region ipsilateral to the
      hippocampal lesion at any time point examined. Additionally, immunocytochemical
      localization of nonphosphorylated and phosphorylated neurofilament proteins did
      not reveal abnormal staining characteristics within the septal/diagonal band
      complex, suggesting that this lesion does not alter cytoskeletal features of
      neurons which project to the hippocampus. Selected rats received unilateral
      hippocampal lesions and 3 months later were injected with fluorogold into the
      remaining hippocampal remnant and with wheat germ agglutinin conjugated to horse
      radish peroxidase into the intact contralateral hippocampus. Both retrograde
      tracers were predominantly transported to their respective ipsilateral septum and
      vertical limb of the diagonal band. This indicates that following the lesion,
      septal/diagonal band neurons still project ipsilaterally and sprouting to the NGF
      rich contralateral side does not occur. RNA blot analysis revealed a decrease in
      NGF mRNA expression within the lesioned hippocampus with a maximum reduction of
      approximately 70%. In contrast, no change in NGF mRNA expression was observed
      within the ipsilateral septum relative to the contralateral side. The present
      study demonstrates that removal of hippocampal target neurons does not alter the
      number, morphology, or projections of both cholinergic and noncholinergic
      septal/diagonal band neurons.

PMID- 1377635
TI  - Sabeluzole, a memory-enhancing molecule, increases fast axonal transport in
      neuronal cell cultures.
AB  - Morphological rearrangements, such as synapse number changes, have been observed
      in the adult mammalian brain after various experimental paradigms of learning and
      behavioral experience. The role of axonal transport in the physical translocation
      of material during this form of brain plasticity has not been fully appreciated.
      We show here by quantitative video microscopy that sabeluzole (R58735), a new
      memory-enhancing drug in humans, effectively increases fast axonal transport in
      rat neuronal cell cultures. Long-term incubation (24 hr) with sabeluzole in the
      concentration range between 0.1 and 1 microM increases both velocity and jump
      length of saltatory movements maximally by 20-30% in embryonic hippocampal
      neurons. Acute treatment only increases the velocity by 15-20%. Furthermore, the
      inhibition of axonal transport by 0.1 mM vanadate in N4 neuroblastoma cells is
      reversed by 1 microM sabeluzole. Observations on the kinesin-induced microtubule
      mobility in a reconstituted system show a 10% enhancement by sabeluzole at an
      optimal concentration of 2 microM, but no increase in kinesin ATPase activity. To
      our knowledge, this is the first pharmacological compound shown to increase fast
      axonal transport. The mechanism of fast axonal transport enhancement is discussed
      as a rationale for new therapeutic treatment in neuropathology.

PMID- 1377636
TI  - Electrical field effects on crushed nerve regeneration.
AB  - The delivery of an electrical field to a transected nerve has been shown to
      enhance the regeneration. This study examined the effects of such fields on the
      regeneration of crushed rat sciatic nerve during the first postoperative month.
      The treated (T) nerve group received a battery implant delivering 10 microA with
      the cathode at the distal stump. The recovery was compared to an untreated (UT)
      group and unoperated controls (C). The loss of locomotion behavior and partial
      recovery (SFI) was identical for the T and UT groups. The index of motor recovery
      (twitch tension) was also similar (T/C = 48%, UT/C = 53%), but a "window" of
      enhancement occurred 2-4 days earlier in the T group. Qualitative histology at 28
      days suggested a more healthy and normal-appearing nerve in the T group.
      Morphometric analysis indicated that the nerve area, fiber density, and fiber
      number in the T group were more similar to those in the control group than to
      those in the UT group. There were no group differences in the number of HRP
      labeled motoneurons, but the enlarged endoneurial space was significantly reduced
      in the T group compared to the UT group. In conclusion, electrical fields
      appeared to have a small effect on some aspects of nerve regeneration following
      crush injury.

PMID- 1377637
TI  - The extracellular matrix of rat spinal cord: a comparative study on the
      localization of hyaluronic acid, glial hyaluronate-binding protein, and
      chondroitin sulfate proteoglycan.
AB  - The localization of hyaluronic acid (HA), glial hyaluronate-binding protein
      (GHAP), and chondroitin sulfate (CS) proteoglycan was compared in cryostat
      sections of rat spinal cord. HA, GHAP, and CS proteoglycan were similarly
      distributed in white matter where they surrounded myelinated axons. In gray
      matter, large motoneurons were surrounded by a rim of reaction product in
      sections stained for HA and CS proteoglycan. GHAP immunoreactivity as well as HA
      had disappeared in hyaluronidase-digested sections, while CS proteoglycan
      immunoreactivity was not abolished under these conditions.

PMID- 1377638
TI  - Conservation analysis and structure prediction of the SH2 family of
      phosphotyrosine binding domains.
AB  - Src homology 2 (SH2) regions are short (approximately 100 amino acids), non
      catalytic domains conserved among a wide variety of proteins involved in
      cytoplasmic signaling induced by growth factors. It is thought that SH2 domains
      play an important role in the intracellular response to growth factor stimulation
      by binding to phosphotyrosine containing proteins. In this paper we apply the
      techniques of multiple sequence alignment, secondary structure prediction and
      conservation analysis to 67 SH2 domain amino acid sequences. This combined
      approach predicts seven core secondary structure regions with the pattern beta
      alpha-beta-beta-beta-beta-alpha, identifies those residues most likely to be
      buried in the hydrophobic core of the native SH2 domain, and highlights patterns
      of conservation indicative of secondary structural elements. Residues likely to
      be involved in phosphotyrosine binding are shown and orientations of the
      predicted secondary structures suggested which could enable such residues to
      cooperate in phosphate binding. We propose a consensus pattern that encapsulates
      the principal conserved features of the SH2 domains. Comparison of the proposed
      SH2 domain of akt to this pattern shows only 12/40 matches, suggesting that this
      domain may not exhibit SH2-like properties.

PMID- 1377639
TI  - D-glyceraldehyde-3-phosphate dehydrogenase purified from rabbit muscle contains
      phosphotyrosine.
AB  - Homogeneous preparations of D-glyceraldehyde-3-phosphate dehydrogenase purified
      from rabbit muscle were found to contain 0.2-0.7 moles of covalently bound
      phosphate per mole of the enzyme. With the use of anti-phosphotyrosine
      antibodies, evidence was obtained that the enzyme is phosphorylated at tyrosine
      residues.

PMID- 1377640
TI  - Membrane-bound apolipoprotein B is exposed at the cytosolic surface of liver
      microsomes.
AB  - We have used a competitive enzyme-linked immunoassay with a panel of monoclonal
      antibodies to probe the topography of the membrane-bound form of apolipoprotein B
      (apo B) in rabbit microsomes. All epitopes investigated were found to be
      expressed at the cytosolic side of the microsomal membrane under conditions in
      which the vesicles remained sealed. These results indicate that the membrane
      associated form of apolipoprotein B is either at the cytosolic side of the
      endoplasmic reticulum membrane or integrated into the membrane. From this site
      apo B may be translocated to the lumen for assembly into VLDL or may be degraded.

PMID- 1377641
TI  - Extracellular 2-chloroadenosine and ATP stimulate volume-sensitive Cl- current
      and calcium mobilization in human tracheal 9HTEo- cells.
AB  - The perforated-patch whole-cell technique was used to record membrane currents in
      epithelial cells (9HTEo-) obtained from the human tracheal epithelium.
      Extracellular application of 2-chloroadenosine and ATP (0.01-100 microM) caused
      activation of Cl- currents similar to those regulated by cell volume in airway
      and intestinal cells. This response was inhibited by increasing extracellular
      osmolality, by omission of extracellular Ca2+, or by the addition of the A2
      adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX).
      Fluorimetric measurements with fura-2 reveal that 2-chloroadenosine and ATP
      elicited both a Ca2+ influx through the plasma membrane and a release from
      intracellular stores.

PMID- 1377642
TI  - Membrane-derived oligosaccharides (MDO's) promote closing of an E. coli porin
      channel.
AB  - The outer membrane of Escherichia coli is a diffusion barrier for macromolecules,
      but allows the passage of small hydrophilic solutes through non-specific
      channels, the porins. Some electrophysiological studies find reconstituted porins
      in a mostly open state, while those done with the patch-clamp technique performed
      on live cells suggest that the vast majority of the native channels are closed.
      We present here current measurements through porins from reconstituted outer
      membrane, which demonstrate that bacterial metabolites, the MDO's, which bathe
      the periplasmic side of the outer membrane, induce the channels to close. These
      findings illustrate that the degree of openness of porins can be regulated by
      compounds naturally found in bacteria.

PMID- 1377643
TI  - Multiple Ca2+ signaling pathways converge on CaM kinase in PC12 cells.
AB  - The role of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase)
      in mediating various Ca2+ signaling pathways was examined in PC12 cells.
      Conversion of the kinase to a Ca(2+)-independent form was used to monitor which
      neurotransmitters activate the enzyme in situ. CaM kinase responds to Ca2+ influx
      elicited by ligand-gated Ca2+ channels for ATP and acetylcholine. It also
      responds to Ca2+ mobilization of IP3-sensitive stores elicited by phospholipase C
      linked receptors for ATP and acetylcholine as well as by caffeine. CaM kinase
      mediates the actions of many neurotransmitters and Ca2+ signaling pathways.

PMID- 1377645
TI  - Specific increase of a mitochondrial RNA transcript in chronic ethanol-fed rats.
AB  - An in vitro transcription system utilizing isolated mitochondria has been used to
      study the effect of chronic ethanol consumption on liver mitochondrial DNA
      transcription. The results obtained showed an overall increase of RNA synthesis
      and a dramatic accumulation of a discrete polyadenylated RNA species. This effect
      is a consequence of the chronic ethanol consumption since these changes do not
      occur when isolated control mitochondria are incubated in the presence of
      ethanol.

PMID- 1377644
TI  - Effects of antiarrhythmic drugs on phospholipid metabolism in Jurkat T cells. The
      potassium channel blocker, clofilium, specifically increases phosphatidylserine
      synthesis.
AB  - Five antiarrhythmic drugs (bretylium, clofilium, propranolol, N
      acetylprocainamide and amiodarone) were tested for their ability to modify
      phospholipid metabolism in Jurkat T lymphocytes. The five drugs, decreased in a
      dose-dependent mode the biosynthesis of both phosphatidylcholine and
      phosphatidylethanolamine, this effect was essentially due to impairment of either
      choline or ethanolamine uptake by the cells. The efficiency of the drugs to
      inhibit phosphatidylcholine and phosphatidylethanolamine synthesis was in the
      order: clofilium greater than amiodarone much greater than propranolol =
      bretylium much greater than N-acetylprocainamide. The IC50 varied from 3-5 microM
      for clofilium to greater than 200 microM for N-acetylprocainamide. In contrast,
      only clofilium, a voltage-gated K(+)-channel blocker, was able to increase
      phosphatidylserine synthesis with an EC50 = 50 microM. The effect of clofilium on
      phosphatidylserine synthesis thus mimics the effect of three other K(+)-channel
      blockers, quinine, 4-aminopyridine and tetraethylammonium, suggesting close
      relationships between phosphatidylserine synthesis and K+ channel activity.

PMID- 1377647
TI  - Characterization of carbohydrates in the alpha 2-macroglobulin receptor.
AB  - Carbohydrates were characterized in the human placental alpha 2-macroglobulin
      receptor and its associated protein. Carbohydrates, largely N-linked, contributed
      to about 18% of the size of the receptor alpha-chain and to about 25% of the beta
      chain. The 40 kDa receptor-associated protein also contained carbohydrate. The
      alpha- and beta-chains contained a wide variety of carbohydrates as judged by
      binding of lectins. Monosaccharide-competing inhibition of alpha 2M-methylamine
      binding by WGA suggested a functional significance of sugars in binding of
      ligands to the alpha-chain.

PMID- 1377646
TI  - A possible role for cysteine residues in the fidelity of DNA synthesis exhibited
      by the reverse transcriptases of human immunodeficiency viruses type 1 and type
      2.
AB  - HIV reverse transcriptases (RTs) have few cysteine residues relative to other RTs
      and retain their DNA polymerization functions following chemical modification by
      thiol-specific reagents. The functional role of the cysteines in the fidelity of
      the DNA-dependent DNA synthesis of HIV RTs has been addressed by chemical
      modification of the wild-type enzymes in combination with the analysis of an
      enzymatically active mutant HIV-1 RT in which all cysteines were modified to
      serines. We have observed an increase in 3'-terminal mispair extension efficiency
      exhibited by chemically modified HIV-1 and HIV-2 RTs. The possible involvement of
      cysteine residues was further substantiated using the cysteine-free mutant HIV-1
      RT that displays an increased efficiency of mispair extension. These results
      provide evidence for a possible role of cysteine residues in the fidelity of DNA
      synthesis catalyzed by HIV RTs.

PMID- 1377648
TI  - Stereospecific assignments and chi 1 rotamers for FKBP when bound to ascomycin
      from 3JH alpha,H beta and 3HN,H beta coupling constants.
AB  - 3JH alpha,H beta and 3JN,H beta coupling constants were measured for isotopically
      labeled FKBP when bound to the immunosuppressant, ascomycin, using a 1H-coupled
      3D HCCH-TOCSY and 15N-coupled 3D HSQC-TOCSY experiment, respectively. From an
      analysis of these two sets of coupling constants, stereospecific beta-proton
      assignments and chi 1 rotamers for FKBP have been obtained. All of the chi 1
      rotamers were consistent with the chi 1 angles measured in the X-ray crystal
      structure of the FKBP/FK506 complex, suggesting that the structures of the two
      complexes are similar.

PMID- 1377649
TI  - Stimulation of human nitric oxide synthase by tetrahydrobiopterin and selective
      binding of the cofactor.
AB  - To check the stimulatory potency of the tetrahydro forms of the two major
      pteridines occurring in human tissues, neopterin and biopterin, NO synthase was
      purified 6000-fold from human cerebellum. Tetrahydrobiopterin stimulated the
      activity up to 4.5-fold in a concentration dependent manner with a maximum above
      1 microM, whereas tetrahydroneopterin was completely inactive in concentrations
      up to 100 microM. Tetrahydrobiopterin, but not neopterin derivatives, were
      copurified with the NO synthase activity. Our results demonstrate that human
      cerebellum contains a tetrahydrobiopterin dependent NO synthase activity.

PMID- 1377650
TI  - Functional studies on Calliphora vomitoria haemocyte subpopulations defined by
      lectin staining and density centrifugation.
AB  - Haemocyte subpopulations of Calliphora vomitoria have been categorized by their
      surface staining properties using fluorescently labelled lectins, and their
      mobilities in Percoll density gradients. These methods of identification were
      exploited to determine the roles of these cell types in cellular defence
      reactions. Soybean agglutinin clearly defined the cell subpopulation involved in
      phagocytosis, while purified thrombocytoid fragments proved to be the main
      haemocyte population involved in encapsulation and nodule formation.

PMID- 1377651
TI  - Purification and characterization of a galactose-specific agglutinin from the
      haemolymph of the larval stages of the insect Calliphora vomitoria.
AB  - A lectin was isolated from the haemolymph of the blowfly larva Calliphora
      vomitoria. It agglutinated a variety of mammalian erythrocytes with varying
      specificities and was strongly inhibited by D-galactose and fetuin. The activity
      was also sensitive to chelators of metal ions, heating above 50 degrees C and
      proteolytic digestion. SDS-PAGE identified a glycoprotein with an Mr of 32,000
      under reducing and nonreducing conditions which resolved to a band at pH 5.4
      using isoelectric focusing. Using FPLC gel filtration the activity was isolated
      in a fraction with an Mr of 130,000. It is suggested that the native form of the
      molecule is a noncovalently associated tetramer.

PMID- 1377652
TI  - Interactions of the lepidotrichial matrix components during tail fin regeneration
      in teleosts.
AB  - Teleost fin rays are able to regenerate, when they are cut, restoring the whole
      structure in a few weeks. Following the formation and growth of an apical
      blastema, deposition of lepidotrichial matrix occurs. We have histo and
      immunochemically analyzed the maturation process of the lepidotrichial
      hemisegment, pointing out the interactions between their components and likewise
      the temporal and spatial distribution of some extracellular matrix components
      during regeneration. Lepidotrichial matrix is rich in sulfated glycosaminoglycans
      (GAGs), most of which are forming proteoglycans. Collagen is abundant and it
      strongly interacts with GAGs, as the tissue differentiates. The use of specific
      digestions with papain and collagenase suggests that some mannose rich
      glycoproteins may be also implicated in lepidotrichial maturation before
      mineralization. In each hemisegment a central band (CB) can be observed. In spite
      of the histochemical similarities between the CB and the subepidermical basement
      membrane, neither collagen IV nor laminin are present. This CB could be the
      result of a transient transdifferentiation of the outer lepidotrichial
      synthesizing cells.

PMID- 1377653
TI  - Monoclonal antibodies raised against pre-migratory neural crest reveal population
      heterogeneity during crest development.
AB  - In order to address the problem of when heterogeneity arises within premigratory
      and early migratory neural crest cell populations, mouse monoclonal antibodies
      were raised against quail premigratory neural crest. Due to the limited
      availability of immunogen an intrasplenic route for immunization was used. Three
      monoclonal antibodies (referred to as LH2D4, LH5D3 and LH6C2) were subsequently
      isolated which recognized subpopulations in 24 h cultures of both quail and chick
      mesencephalic and trunk neural crest in immunocytochemical studies. Subsequent
      investigations using a range of six antibodies, including LH2D4, LH5D3 and LH6C2,
      showed that population heterogeneity (which was not cell cycle related) could be
      detected as early as 15 h following mesencephalic crest explantation, a stage at
      which all the neural crest cells were morphologically identical. However,
      premigratory neural crest from the same axial level of origin was homogeneous, as
      judged by immunoreactivity patterns with these antibodies. Significant
      differences were found in the proportion of immunoreactive cells between
      populations of mesencephalic and trunk neural crest cultures. Double
      immunofluorescence studies revealed the existence of at least four separate cell
      populations within individual crest cultures, each identified by their unique
      antibody reactivity pattern, thus providing some insight into the underlying
      complexity of subpopulation composition within the neural crest.
      Immunocytochemical studies on quail embryos from stages 7-22 showed that the
      epitopes detected by LH2D4, LH5D3 and LH6C2 were not necessarily confined to the
      neural crest or to cells of crest derivation. All three epitopes displayed a
      spatiotemporal regulation in their expression during early avian ontogeny. Since
      the differential epitope expression described in this investigation was
      detectable as early as 15 h after premigratory neural crest explantation, took
      place in vitro in the absence of any other cell type and changed progressively
      with time, we conclude that a certain degree of population heterogeneity can be
      generated very early in neural crest ontogeny and independently of the tissue
      interactions that normally ensue in vivo.

PMID- 1377654
TI  - Cultured aortic smooth muscle cells from newborn and adult rats show distinct
      cytoskeletal features.
AB  - It is well known that arterial smooth muscle cells (SMC) of adult rats, cultured
      in a medium containing fetal calf serum (FCS), replicate actively and lose the
      expression of differentiation markers, such as desmin, smooth muscle (SM) myosin
      and alpha-SM actin. We report here that compared to freshly isolated cells,
      primary cultures of SMC from newborn animals show no change in the number of
      alpha-SM actin containing cells and a less important decrease in the number of
      desmin and SM myosin containing cells than that seen in primary cultures of SMC
      from adult animals; moreover, contrary to what is seen in SMC cultured from adult
      animals, they show an increase of alpha-SM actin mRNA level, alpha-SM actin
      synthesis and expression per cell. These features are partially maintained at the
      5th passage, when the cytoskeletal equipment of adult SMC has further evolved
      toward dedifferentiation. Cloned newborn rat SMC continue to express alpha-SM
      actin, desmin and SM myosin at the 5th passage. Thus, newborn SMC maintain, at
      least in part, the potential to express differentiated features in culture.
      Heparin has been proposed to control proliferation and differentiation of
      arterial SMC. When cultured in the presence of heparin, newborn SMC show an
      increase of alpha-SM actin synthesis and content but no modification of the
      proportion of alpha-SM actin total (measured by Northern blots) and functional
      (measured by in vitro translation in a reticulocyte lysate) mRNAs compared to
      control cells cultured for the same time in FCS containing medium. This suggests
      that heparin action is exerted at a translational or post-translational level.
      Cultured newborn rat aortic SMC furnish an in vitro model for the study of
      several aspects of SMC differentiation and possibly of mechanisms leading to the
      establishment and prevention of atheromatous plaques.

PMID- 1377655
TI  - Characterization and cell type distribution of a novel, major transcript of the
      Duchenne muscular dystrophy gene.
AB  - Previously we identified a novel 6.5 kb mRNA transcribed from the Duchenne
      muscular dystrophy (DMD) gene. This mRNA differs in coding content and tissue
      distribution from the known muscle type and brain type 14 kb DMD mRNAs which code
      for dystrophin. The novel transcript shares with dystrophin most of the sequence
      coding for the cysteine-rich and C-terminal domains. Here we used cDNA cloning to
      identify the divergence point between the common region and the sequence unique
      to the novel mRNA at the 5' end of the sequence encoding the cysteine-rich domain
      of dystrophin. This unique sequence containing the translation initiation site is
      located in a new exon in the intron between exons 62 and 63 of the dystrophin
      gene. Using probes containing RNA sequences specific to the novel mRNA, we
      investigated the expression of this mRNA in various tissues and cell types. The
      study reveals that this mRNA is the main DMD gene product detectable in a variety
      of nonmuscle tissues including brain cells. The amount of this mRNA in some
      tissues is comparable to the amount of dystrophin mRNA in the muscle. The
      expression of the 6.5 kb mRNA is down-regulated during differentiation of
      myogenic cells; it is present in small amounts in proliferating myoblasts but is
      undetected in differentiated muscle cultures depleted of mononucleated cells.

PMID- 1377656
TI  - Characterization of sciellin, a precursor to the cornified envelope of human
      keratinocytes.
AB  - The cornified envelope, located beneath the plasma membrane of terminally
      differentiated keratinocytes, is formed as protein precursors are cross-linked by
      a membrane associated transglutaminase. This report characterizes a new precursor
      to the cornified envelope. A monoclonal antibody derived from mice immunized with
      cornified envelopes of human cultured keratinocytes stained the periphery of more
      differentiated cells in epidermis and other stratified squamous epithelia
      including hair and nails. The epitope was widely conserved among mammals as
      determined by immunohistochemical and Western analysis. Immunoelectron microscopy
      localized the epitope to the cell periphery in the upper stratum spinosum and
      granulosum of epidermis. In the hair follicle, the epitope was present in the
      internal root sheath and in the infundibulum, the innermost aspect of the
      external root sheath. The antibody recognized a protein of relative mobility
      (M(r)) 82,000, pI 7.8. The protein was a transglutaminase substrate as shown by a
      dansylcadaverine incorporation assay. Purified cornified envelopes absorbed the
      reactivity of the antibody to the partially purified protein and cleavage of
      envelopes by cyanogen bromide resulted in release of immunoreactive fragments.
      The protein was soluble only in denaturing buffers such as 8 M urea or 2% sodium
      dodecyl-sulfate (SDS). Partial solubility could be achieved in 50 mM TRIS pH 8.3
      plus 0.3 M NaCl (high salt buffer); the presence of a reducing agent did not
      affect solubility. Extraction of cultured keratinocytes in 8 M urea and
      subsequent dialysis against 50 mM TRIS pH 8.3 buffer resulted in precipitation of
      the protein with the keratin filaments. Dialysis against high salt buffer
      prevented precipitation of the protein. The unique solubility properties of this
      protein suggest that it aggregates with itself and/or with keratin filaments. The
      possible role of the protein in cornified envelope assembly is discussed. We have
      named this protein Sciellin (from the old english "sciell" for shell).

PMID- 1377657
TI  - Prognostic factors in patients with hepatocellular carcinoma receiving systemic
      chemotherapy.
AB  - A total of 71 consecutive patients with unresectable hepatocellular carcinoma
      were analyzed retrospectively to determine the significant prognostic factors.
      All the patients received systemic chemotherapy in a phase 2 study from 1980 to
      1990, with no other anticancer treatment. Median survival time and 1-yr and 2-yr
      survival rates were 5.6 mo, 23% and 5%, respectively. By the univariate analysis,
      a performance status of 0-1 and tumor size less than 50% of the liver cross
      sectional area were shown to be the factors most significantly favoring a better
      prognosis. By the multivariate analysis using the Cox proportional hazards model,
      a performance status of 0-1 (p less than 0.001), absence of tumor thrombus in the
      main portal trunk (p = 0.003) and age less than 60 yr (p = 0.036) were
      independent favorable prognostic factors. A prognostic index was calculated from
      these three factors according to the following equation: 1.8109 x (0 =
      performance status of 0-1 and 1 = performance status of 2-3) + 0.9322 x (0 =
      tumor thrombus absent in the main portal trunk and 1 = present) + 0.6996 x (0 =
      age less than 60 yr and 1 = age greater than or equal to 60 yr). This index was
      used to classify the patients into three groups with a good, intermediate and
      poor prognosis. The median survival times for these three groups were 9.8, 3.8
      and 1.9 mo, respectively (p less than 0.01). The results of this study may be
      useful in the design and analysis of future clinical trials of systemic therapy
      for hepatocellular carcinoma.

PMID- 1377658
TI  - Defective methionine metabolism in cirrhosis: relation to severity of liver
      disease.
AB  - A block in the transsulfuration pathway has previously been suggested in
      cirrhosis on the basis of increased fasting methionine concentrations, decreased
      methionine elimination and low levels of methionine end products. To date,
      methionine elimination has never been studied under controlled steady-state
      conditions, and the relation of the severity of liver disease to impaired
      methionine metabolism has not been clarified. We measured methionine plasma
      clearance in 6 control subjects and in 12 patients with cirrhosis during steady
      state conditions obtained by a primed, continuous methionine infusion. In the
      presence of high-normal fasting methionine concentrations (range = 14 to 69
      mumol.L-1 in controls and 26 to 151 mumol.L-1 in cirrhotic patients), methionine
      plasma clearance was reduced in cirrhotic patients (2.25 +/- S.D. 0.43 ml.sec-1
      vs. 2.86 +/- S.D. 0.43 ml.sec-1 in controls; p less than 0.05), whereas
      methionine half-life was increased (282 +/- 90 min vs. 187 +/- 25 min in
      controls; p less than 0.05). Fasting methionine significantly correlated with
      methionine clearance. The infused methionine was not degraded to urea to any
      significant extent in cirrhotic patients, whereas a threefold increase in urinary
      urea nitrogen excretion rate was observed in controls. Similarly, taurine
      concentrations significantly increased both in plasma and in the urine in
      controls but not in cirrhotic patients. In cirrhotic patients methionine plasma
      clearance significantly correlated with galactose elimination capacity (r =
      0.818) and with the Child-Pugh score (rs = -0.795). The study supports a major
      role of impaired liver cell function in the reduced metabolism of methionine and
      decreased formation of methionine end products that occur in cirrhosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377659
TI  - Frequency of delta F508 and haplotype association in Austrian cystic fibrosis
      families.
AB  - The frequency of the major mutation in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene was analyzed for 113 Austrian cystic fibrosis
      (CF) patients. An overall frequency of 55% for delta F508 was found with values
      of 72% and 13% for patients with pancreatic insufficiency (CF-PI) and those with
      pancreatic sufficiency (CF-PS), respectively. Furthermore, the distribution of
      the alleles of the closely linked DNA markers XV2c/KM19/MP6d-9 in our families is
      described.

PMID- 1377660
TI  - Frequency of delta F508 mutation and haplotype analysis in Austrian cystic
      fibrosis families.

PMID- 1377661
TI  - Internalization of CD4 molecules in human T-cells demonstrated by immuno-electron
      microscopy.
AB  - Internalization of CD4 molecules on human CD4-enriched T-cells was demonstrated
      by immunocytochemical electron microscopy. CD4+ T-cell subclones were obtained
      from normal human peripheral blood, followed by one-way MLC screening and co
      culturing with IL-2. Fixed and non-fixed T-cell samples were indirectly
      immunolabeled with mouse anti-human CD4 monoclonal antibody and goat anti-mouse
      IgG conjugated with peroxidase. Unfixed T-cells were immunolabeled at 4 degrees C
      and then re-incubated for 5-45 min at 37 degrees C. The selected CD4+ T-cell
      subclones showed strong CD4 binding on the cell surface after IL-2 incubation.
      However, fresh T-cells, monocytes, bone marrow cells and CD8+ T-cells all stained
      negative for CD4. The distribution of CD4 molecules on the fixed cell surface
      showed a homogeneous pattern. Capping and internalization of CD4-antibody
      peroxidase complexes from the cell surfaces were observed follow a pathway of
      receptor-mediated endocytosis in unfixed T cells. Endocytotic vesicles, vacuoles
      of diverse sizes and shapes near the cell membrane or deep in the cell center
      were found to contain CD4 molecules. Negatively stained Golgi saccules were
      observed up to 45 min after re-incubation. These results suggest that increased
      CD4 molecules can be induced on the surface of normal human T-cells in vitro.
      Internalization and accumulation of CD4 molecules occurred in CD4-enriched T
      cells with IL-2 pretreatment.

PMID- 1377662
TI  - Histochemical changes in the rabbit cornea and plasmin activity in the tear fluid
      during contact lens wear. Favourable influence of protease inhibitors (aprotinin,
      PC5, elastatinal).
AB  - Plasmin activity in the tear fluid of the rabbit eye was examined during the
      wearing of soft contact lenses (SCL) and compared with the occurrence of corneal
      disturbances assessed in cryostat sections. Plasmin activity was determined with
      a semiquantitative method using dry punches of filter paper previously soaked in
      0.1 M Tris-HCl buffer solution containing mmol/l D-Val-Leu-Lys-FCA
      (trifluoromethylaminocoumarine), pH 7.2. Punches were applied to the corneal
      surface for 5 s (tear collection) and incubated in wet chamber. The time of
      appearance of the bright yellow fluorescence in UV light was recorded and taken
      as a measure of plasmin activity. For calibration punches soaked in solutions
      containing plasmin in various concentrations, and processed in the same manner
      were used. Changes in the cornea were examined histochemically using methods of
      choice for acid glycosidases, proteases, dehydrogenases, and Na(+)-K(+)-ATPase.
      SCL with high and low water content were worn in rabbits in 1, 2, 4, 7, 14, 21
      and 28 days. Decreased activity of Na(+)-K(+)-ATPase, GGT, and SDH in the corneal
      endothelium and epithelium were not accompanied by detectable plasmin activity in
      the tear fluid. Pronounced damage of the corneal epithelium (increased activities
      of acid glycosidases, acid proteases, LDH, markedly decreased activity of SDH)
      was accompanied by low concentration of plasmin (0.4-1.0 micrograms/ml) in the
      tear fluid. Middle activity of plasmin (1.0-2.0 micrograms/ml) was detectable
      when PMNs were present in the corneal stroma. High plasmin activity (2.0-3.0
      micrograms/ml) correlated with corneal ulceration and vascularization.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377663
TI  - Effects of monomeric acrylic embedding media on the antigenicity of two epitopes
      of the MIC2-encoded Ewing's sarcoma cell membrane antigen.
AB  - Comparative electron microscopic studies of pre- and postembedding immunolabeling
      experiments have shown that the antigenicity of some epitopes is lost during
      acrylic resin embedding of the respective tissues. In the present investigation
      we have tested the sensitivities of two embedding-labile epitopes (HBA-71 and HBA
      45) of the Ewing's sarcoma-associated MIC2-encoded E2 antigen to the effects of
      the different treatment steps, which are necessary for the preparation of
      ultrathin sections. The extent of antigenic retention was quantitated using flow
      cytometry and enzyme-linked immunosorbent assays (ELISA) of tumor cell lines,
      thymocytes and cell membrane extracts. Fixation, dehydration and high temperature
      treatment of MIC2-positive cells showed only minor effects on the reactivity with
      the HBA-71 and HBA-45 antibodies. However, exposure of the cells to the monomeric
      acrylic resins LR White (LRW), LR Gold (LRG) and Lowicryl K4M at 4 degrees C for
      2-18 h resulted in a significant reduction of the HBA-71 and HBA-45 reactivities.
      In contrast, the antigenicity of both epitopes was maintained during treatment
      with the apolar Lowicryl HM20 embedding medium under these non-polymerizing
      conditions. The resins have no direct effect on the HBA-71/HBA-45 antigen, since
      it could be extracted in intact form from membranes of native, but not of fixed,
      tumour cells using LRW for membrane solubilization. These data indicate that the
      HBA-71/HBA-45 antigen remains in the cell membrane and is indirectly influenced
      by the extraction/modification of adjacent membrane constituents. The adverse
      effects of the polymerization process, in the case of embedding at low
      temperature in Lowicryl HM20, destroyed MIC2-antigenicity.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1377664
TI  - Co-localization of nitric oxide synthase immunoreactivity and NADPH diaphorase
      staining in neurons of the guinea-pig intestine.
AB  - Neuronal nitric oxide synthase (NOS), an enzyme capable of synthesizing nitric
      oxide, appears to be identical to neuronal NADPH diaphorase. The correlation was
      examined between NOS immunoreactivity and NADPH diaphorase staining in neurons of
      the ileum and colon of the guinea-pig. There was a one-to-one correlation between
      NOS immunoreactivity and NADPH diaphorase staining in all neurons examined; even
      the relative staining intensities obtained were similar with each technique. To
      determine whether pharmacological methods could be employed to demonstrate that
      NADPH diaphorase staining was due to the presence of NOS, tissue was pre-treated
      with NG-nitro-L-arginine, a NOS inhibitor, or L-arginine, a natural substrate of
      NOS. In these experiments on unfixed tissue, it was necessary to use dimethyl
      thiazolyl tetrazolium instead of nitroblue tetrazolium as the substrate for the
      NADPH diaphorase histochemical reaction. Neither treatment caused a significant
      decrease in the level of NADPH diaphorase staining, implying that arginine and
      NADPH interact at different sites on the enzyme.

PMID- 1377665
TI  - Brain microdialysis study of the effects of hazardous chemicals on the central
      nervous system. 1. Changes in monoamine metabolites induced by cerebral methyl
      bromide administration measured by two-probe microdialysis (TPMD) method.
AB  - The two-probe microdialysis (TPMD) method, in which two probes were applied
      simultaneously to the rat head, was developed to directly investigate the effects
      of chemicals on the brain. The first and the second probes were implanted into
      the right striatum and the left ventricle, respectively. Chemicals were dissolved
      in the perfusion fluid and given into the brain by diffusion through the
      ventricle probe. Monoamine metabolites were recovered through the striatum probe
      to investigate changes in neurotransmitter substances. Both intraperitoneal and
      intraventricular administration of haloperidol (a dopamine receptor blocker)
      increased 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA,
      dopamine metabolites) concentrations in the striatum. On the other hand,
      apomorphine (a dopamine receptor stimulant), which was given both
      intraperitoneally and intraventricularly, decreased striatal DOPAC and HVA
      concentrations. 5-Hydroxyindoleacetic acid (5HIAA, a serotonin metabolite)
      concentration was not affected by these drugs. Regarding changes in monoamine
      neurotransmitters, systemic and intraventricular administration produced similar
      effects. These findings indicate that the drugs were effectively incorporated
      into the brain by the TPMD method and the drug effect was observed in the
      opposite brain hemisphere. In the same procedure as used in the administration of
      haloperidol and apomorphine, methyl bromide was given into the rat brain. DOPAC
      and HVA in the striatum were increased by methyl bromide given by the TPMD
      method. These changes were the same as observed in the homogenate of rat brain
      exposed to methyl bromide. 5HIAA was reduced by intraventricular administration
      by the TPMD method, and this change in 5HIAA was not observed in the exposure
      experiments. We could detect the direct effects of methyl bromide on the brain by
      the TPMD method.

PMID- 1377666
TI  - Localization and characterization of serologic epitopes on HLA-A2.
AB  - A panel of cells expressing 68 different mutant HLA-A2 genes was generated by
      site-directed mutagenesis and DNA-mediated gene transfer in order to define the
      regions of class I MHC molecules that contribute to the epitopes recognized by
      mAb. Each of the variant HLA-A2 molecules differed from HLA-A2.1 by a single
      amino acid substitution. The substitutions were located in both the alpha-helices
      and beta-strands of the alpha 1 and alpha 2 domains, and included residues that
      are highly polymorphic and that are conserved. All but five of the variant HLA-A2
      molecules were expressed at levels that ranged from approximately 25%-100% the
      levels found for HLA-A2.1. The remaining five variants had no detectable
      expression and all involved substitutions at highly conserved residues. Eleven
      mAbs with specificities that ranged from highly HLA-A2 specific to monomorphic
      were analyzed for their ability to bind the variant HLA-A2 molecules. The results
      demonstrate that the binding of five of 11 mAbs could be mapped to the alpha 1
      and alpha 2 domains. MA2.1 was the only antibody mapped to the alpha 1 domain.
      CR11-351 and A2,A28M1 recognized an overlapping epitope at the amino terminal end
      of the alpha 2-helix, and PA2.1 and BB7.2 recognized an overlapping epitope that
      includes the carboxy terminus of the alpha 2-helix and a turn on one of the
      underlying beta-strands. These results demonstrate that positions located on the
      surface of the molecule, but not within the peptide-binding cleft of the
      molecule, are important in serological specificities.

PMID- 1377667
TI  - Diverse locations of amino acids in HLA-DR beta chains involved in polymorphic
      antibody binding epitopes on DR(alpha, beta 1*0101), DR(alpha, beta 1*1101), and
      DR(alpha,beta 3*0202) molecules.
AB  - In a previous study, we used transfectants expressing hybrid HLA-DR(beta
      1*0403)/DR(beta 1*0701) chains to map sequences involved in polymorphic antibody
      binding epitopes on DR(alpha, beta 1*0403) or DR(alpha, beta 1*0701) molecules.
      Amino acids 1-40 of the beta 1 domain were found to make the major contributions
      to most of the antibody binding epitopes studied. To begin to localize sequences
      that contribute to polymorphic antibody epitopes on DR(alpha,beta 1*0101),
      DR(alpha,beta 1*1101) and DR(alpha,beta 3*0202) molecules, we used indirect
      immunofluorescence and flow cytometry to assess the binding of mAb to
      transfectants expressing hybrid DR(beta 1*0101)/DR(beta 1*1101) or DR(beta
      1*1101)/DR(beta 3*0202) chains that divide the DR beta chain into three segments:
      amino acids 1-40, 41-97, and the beta 2 domain. The results indicate that amino
      acids 41-97 of the beta 1 domain on DR(beta 1*0101), DR(beta 1*1101), or DR(beta
      3*0202) are critical in most of the epitopes, including those recognized by human
      antibodies MP4 and MP12, and mouse mAb GS88.2, I-LR1, 21r5, and 7.3.19.1, whereas
      amino acids 1-40 of DR(beta 1*1101) are critical in the epitope recognized by the
      MCS-7 mAb, and both segments 1-40 and 41-97 of DR(beta 1*1101) are important in
      the epitopes recognized by the I-LR2 and UL-52 mAbs. Based on these data and
      comparison of DR beta allelic protein sequences, the residues that may play
      critical roles in these antibody binding epitopes are predicted.

PMID- 1377668
TI  - Epitopes predominantly retained on the carcinoembryonic antigen molecules in
      plasma of patients with malignant tumors but not on those in plasma of normal
      individuals.
AB  - We have previously reported that a group of monoclonal antibodies (MAbs) to
      carcinoembryonic antigen (CEA), designated Group F MAbs, are able to discriminate
      CEA in tumor tissues from normal fecal antigen-2, a soluble form CEA-counterpart
      in normal adult feces, and that the protein epitopes recognized by them are
      present on the domain A3-B3 of the CEA molecule. In this study, we further
      investigated the molecular localization of the epitopes recognized by the Group F
      MAbs using three new recombinant CEA proteins with restricted domain structures
      expressed in Chinese hamster ovary cells, and found that the epitopes for the
      Group F MAbs are present on domain B3 close to the anchoring device of the CEA
      molecule. The epitopes for the Group F MAbs were retained on the CEA molecules in
      the plasma of patients with malignant tumors and on the CEA molecules
      spontaneously released into the culture media from established tumor cell lines.
      However, a large part of the CEA molecules in the plasma of normal individuals
      were found to lack the epitopes for the Group F MAbs. These results provide a
      basis for the improved cancer diagnosis by using our CEA assay system utilizing a
      Group F MAb, and indicate the potential clinical utility of the Group F MAbs.

PMID- 1377670
TI  - Anti-helix-loop-helix domain antibodies: discovery of autoantibodies that inhibit
      DNA binding activity of human centromere protein B (CENP-B).
AB  - Centromere protein B (CENP-B) is one of the centromere DNA binding proteins
      constituting centromeric heterochromatin of human chromosomes. This protein was
      originally identified as the target antigen in autoimmune disease patients (often
      with scleroderma). In this study, we cloned a human CENP-B cDNA which was longer
      than the previously isolated one and expressed functional recombinant CENP-B in
      Escherichia coli. The DNA binding domain was finely located within the N-terminal
      134-amino-acid residues covering a predicted helix-loop-helix (HLH) structure, by
      using a set of recombinant products with stepwise deletions from the C-terminus.
      From the analysis of their reactivity to anti-centromere sera from autoimmune
      disease patients, four epitopes were mapped on CENP-B antigen. In addition to two
      epitopes at the C-terminus, two were found on the HLH region at the N-terminus.
      In the analysis of the interaction between the antigen and autoantibodies, we
      found that the DNA binding activity of CENP-B was distorted by the attack of the
      anti-HLH domain antibodies in in vitro binding reactions. Our results suggest
      that the direct inhibition of the DNA binding activity by the autoantibodies
      might be involved in patients' autoimmune reactions in vivo.

PMID- 1377671
TI  - Identification and characterization of the cis-elements regulating the rat AMOG
      (adhesion molecule on glia)/Na,K-ATPase beta 2 subunit gene.
AB  - We have identified a positive regulatory cis-acting element of the adhesion
      molecule on glia (AMOG)/Na,K-ATPase beta 2 subunit gene as GAGGCGGGG at position 
      87 to -79 by transient transfection assay using B103 cells (rat neuroblastoma
      cell line). The newly identified AMOG regulatory element (AMRE) enhanced the
      promoter activity in a mutually compensating manner with the Sp1 element at
      position -147 to -142. AMRE acts as a positive regulatory element not only in
      B103 cells but also in 3Y1 (rat embryo cell line) cells to roughly the same
      extent and in MDCK (canine kidney cell line) cells to a lesser extent. AMRE also
      enhances other gene promoters, such as myelin basic protein (MBP) and herpes
      simplex virus (HSV) thymidine kinase (TK) gene promoters. The element is not a
      typical enhancer element because when it is introduced downstream of the HSV TK
      promoter, it has no enhancing activity.

PMID- 1377669
TI  - The inhibitory effect of the combination of antineoplaston A-10 injection with a
      small dose of cis-diamminedichloroplatinum on cell and tumor growth of human
      hepatocellular carcinoma.
AB  - The inhibitory effects of a combination of Antineoplaston A-10 Injection with a
      small dose of cis-diamminedichloroplatinum (CDDP) on cell and tumor growth was
      tested in vitro and in vivo settings. A human hepatocellular carcinoma cell line
      (KIM-1) was used for the cell growth and transplanted tumor growth studies. In
      the cell growth study, one-hour exposure of KIM-1 cells to CDDP in the medium at
      concentrations of 0.5, 1.0, and 2.0 micrograms/ml inhibited cell growth dose
      dependently. Continuous exposure of cultured cells to Antineoplaston A-10
      Injection at concentrations of 4, 6, and 8 mg/ml also inhibited tumor growth dose
      dependently. The combination of 0.5 microgram/ml CDDP and 6 mg/ml A-10 Injection
      inhibited cell growth more than did each agent individually. Electron microscopic
      study showed well-maintained organelle structures in Antineoplaston A-10
      Injection-treated cells compared to CDDP-treated cells. alpha-Fetoprotein (AFP)
      production by 10(4) cells in 48 h increased in the A-10 Injection-treated and A
      10 Injection+CDDP-treated groups as the concentration of these agents increased.
      In the tumor growth study, daily administration of Antineoplaston A-10 Injection
      75 mg with once a week administration of 20 micrograms of CDDP for 5 weeks
      inhibited transplanted tumor growth in athymic mice after 33 days of treatment,
      while administration of 75 mg of A-10 Injection or 20 or 60 micrograms of CDDP
      alone showed no significant inhibition of tumor growth.

PMID- 1377672
TI  - Characterization of recombinant human insulin-like growth factor binding proteins
      4, 5, and 6 produced in yeast.
AB  - The insulin-like growth factor binding protein (IGFBP) family comprises six
      structurally distinct, but highly homologous proteins. They have been identified
      in serum and other biological fluids, tissue extracts, and cell culture media. We
      have recently cloned cDNAs encoding human IGFBP-4, -5, and -6 and have now
      expressed these BPs in yeast as ubiquitin (Ub)-IGFBP fusion proteins. Western
      ligand blotting with 125I-IGF II under nonreducing conditions of recombinant
      human (rh) IGFBP-containing yeast lysates revealed specific binding bands for
      IGFBP-4, -5, and -6 at apparent molecular masses of 24-26, 30-32, and 24-26 kDa,
      respectively, indicating processing of the fusion proteins. High-performance
      liquid chromatography-purified rhIGFBPs had virually the same amino acid
      composition, amino acid number, and NH2-terminal sequences as the native BPs.
      Except for the affinity of rhIGFBP-6 for IGF I (Ka = 8.5 x 10(8) M-1), the
      affinity constants of the three IGFBPs for IGF I and II lie between 1.7 and 3.3 x
      10(10) M-1, i.e. 25-100 times higher than the IGF I and II affinities of the type
      I IGF receptor. When present in excess, rhIGFBP-4, -5, and -6 inhibited IGF I-
      and II-stimulated DNA and glycogen synthesis in human osteoblastic cells, but
      rhIGFBP-6 had only a weak inhibitory effect on IGF I in agreement with its
      relatively lower IGF I affinity constant. The results of this study show that the
      primary effect of the three rhIGFBPs is the attenuation of IGF activity and
      suggest that IGFBPs contribute to the control of IGF-mediated cell growth and
      metabolism.

PMID- 1377673
TI  - Characterization of prostaglandin (PG)-binding sites expressed on human
      basophils. Evidence for a prostaglandin E1, I2, and a D2 receptor.
AB  - Recent data suggest that prostaglandins (PGs) are involved in the regulation of
      basophil activation. The aim of this study was to characterize the basophil PG
      binding sites by means of radioreceptor assays using 3H-labeled PGs. Scatchard
      analysis for pure (greater than 95%) chronic myeloid leukemia (CML) basophils
      revealed two classes of PGE1-binding sites differing in their affinity for the
      natural ligand (Bmax1 = 217 +/- 65 fmol/10(8) cells; Kd1 = 0.5 +/- 0.2 nM; Bmax2
      = 2462 +/- 381 fmol/10(8) cells; Kd2 = 47 +/- 20 nM; IC50 = PGE1 less than PGI2
      less than PGD2 less than PGE2 less than PGF2 alpha) as well as two classes of
      PGI2 (iloprost)-binding sites (Bmax1 = 324 +/- 145 fmol/10(8) cells; Kd1 = 0.5 +/
      0.3 nM; Bmax2 = 2541 +/- 381; Kd2 = 27 +/- 6 nM; IC50 = PGI2 less than PGE1 less
      than PGD2 less than PGE2 less than PGF2 alpha. In addition, CML basophils
      exhibited a single class of PGD2-binding sites (Bmax = 378 +/- 98 fmol/10(8)
      cells; Kd = 13 +/- 4 nM; IC50: PGD2 less than PGI2 less than PGE1 less than PGE2
      less than PGF2 alpha). In contrast, we were unable to detect specific saturable
      PGE2-binding sites. Primary and immortalized (KU812) CML basophils revealed an
      identical pattern of PG receptor expression. Basophils (KU812) expressed
      significantly (p less than 0.001) lower number of PGE1 (PGI2)-binding sites
      (Bmax1: 9% (20%) of control; Bmax2: 36% (50%) of control) when cultured with
      recombinant interleukin 3 (rhIL-3), a basophil-activating cytokine, whereas rhIL
      2 had no effect on PG receptor expression. Functional significance of binding of
      PGs to basophils was provided by the demonstration of a dose-dependent increase
      in cellular cAMP upon agonist activation, with PGE1 (ED50 = 1.7 +/- 1.1 nM) and
      PGI2 (ED50 = 2.8 +/- 2.3 nM) being the most potent compounds. These findings
      suggest that human basophils express specific receptors for PGE1, PGI2 as well as
      for PGD2.

PMID- 1377674
TI  - Phosphorylation of the cystic fibrosis transmembrane conductance regulator.
AB  - Regulation of epithelial chloride flux, which is defective in patients with
      cystic fibrosis, may be mediated by phosphorylation of the cystic fibrosis
      transmembrane conductance regulator (CFTR) by cyclic AMP-dependent protein kinase
      (PKA) or protein kinase C (PKC). Part of the R-domain of CFTR (termed CF-2) was
      expressed in and purified from Escherichia coli. CF-2 was phosphorylated on seryl
      residues by PKA, PKC, cyclic GMP-dependent protein kinase (PKG), and
      calcium/calmodulin-dependent protein kinase I (CaM kinase I). Direct amino acid
      sequencing and peptide mapping of CF-2 revealed that serines 660, 700, 737, and
      813 as well as serine 768, serine 795, or both were phosphorylated by PKA and
      PKG, and serines 686 and 790 were phosphorylated by PKC. CFTR was phosphorylated
      in vitro by PKA, PKC, or PKG on the same sites that were phosphorylated in CF-2.
      Kinetic analysis of phosphorylation of CF-2 and of synthetic peptides confirmed
      that these sites were excellent substrates for PKA, PKC, or PKG. CFTR was
      immunoprecipitated from T84 cells labeled with 32Pi. Its phosphorylation was
      stimulated in response to agents that activated either PKA or PKC. Peptide
      mapping confirmed that CFTR was phosphorylated at several sites identified in
      vitro. Thus, regulation of CFTR is likely to occur through direct phosphorylation
      of the R-domain by protein kinases stimulated by different second messenger
      pathways.

PMID- 1377675
TI  - Reversible binding of platelet-derived growth factor-AA, -AB, and -BB isoforms to
      a similar site on the "slow" and "fast" conformations of alpha 2-macroglobulin.
AB  - The mechanism by which the platelet-derived growth factor (PDGF)-binding protein,
      alpha 2-macroglobulin (alpha 2M), modulates PDGF bioactivity is unknown, but
      could involve reversible PDGF-alpha 2M binding. Herein we report that greater
      than 70% of 125I-PDGF-BB or -AB complexed to alpha 2M was dissociated by SDS
      denaturation followed by SDS-polyacrylamide gel electrophoresis, i.e. most of the
      binding was noncovalent. Reduction of the PDGF.alpha 2M complex following
      denaturation dissociated the cytokine from alpha 2M by greater than 90%,
      suggesting covalent disulfide bond formation. Approximately 50% of the growth
      factor was dissociated by lowering the pH from 7.5 to 4.0. 125I-PDGF-BB bound
      alpha 2M in a time-dependent manner (t1/2 = approximately 1 h), reaching
      equilibrium after 4 h. The 125I-PDGF.BB/alpha 2M complex dissociated more slowly
      (t1/2 = approximately 2.5 h). "Slow" and "fast" alpha 2M bound nearly equal
      amounts of PDGF-AB or -BB. Trypsin treatment converted PDGF-BB/alpha 2M complex
      to the fast conformation but did not release bound 125I-PDGF-BB. All PDGF
      isoforms (AA, -AB, and -BB) competed for binding with 125I-PDGF-BB binding to
      slow alpha 2M and fast alpha 2M-methylamine by 65-80%. Other cytokines that bind
      alpha 2M (transforming growth factor-beta 1 and -beta 2, tumor necrosis factor
      alpha, basic fibroblast growth factor, interleukin -1 beta, and -6) did not
      compete for 125I-PDGF-BB binding slow alpha 2M, but transforming growth factor
      beta 1 and basic fibroblast growth factor inhibited 125I-PDGF-BB binding alpha 2M
      methylamine by 30-50%. The reversible nature of the PDGF.alpha 2M complex could
      allow for targeted PDGF release near mesenchymal cells which possess PDGF
      receptors.

PMID- 1377676
TI  - A panel of monoclonal antibodies for the type I insulin-like growth factor
      receptor. Epitope mapping, effects on ligand binding, and biological activity.
AB  - We obtained 20 mouse monoclonal antibodies specific for human type I insulin-like
      growth factor (IGF) receptors, using transfected cells expressing high levels of
      receptors (IGF-1R/3T3 cells) as immunogen. The antibodies immunoprecipitated
      receptor.125I-IGF-I complexes and biosynthetically labeled receptors from IGF
      1R/3T3 cells but did not react with human insulin receptors or rat type I IGF
      receptors. Several antibodies stimulated DNA synthesis in IGF-1R/3T3 cells, but
      the maximum stimulation was only 25% of that produced by IGF-I. The antibodies
      fell into seven groups recognizing distinct epitopes and with different effects
      on receptor function. All the antibodies reacted with the extracellular portion
      of the receptor, and epitopes were localized to specific domains by investigating
      their reaction with a series of chimeric IGF/insulin receptor constructs. Binding
      of IGF-I was inhibited up to 90% by antibody 24-60 reacting in the region 184
      283, and by antibody 24-57 reacting in the region 440-586. IGF-I binding was
      stimulated up to 2.5-fold by antibodies 4-52 and 16-13 reacting in the region 62
      184, and by antibody 26-3 reacting downstream of 283. The latter two groups of
      antibodies also dramatically stimulated insulin binding to intact IGF-1R/3T3
      cells (by up to 50-fold), and potentiated insulin stimulation of DNA synthesis.
      Scatchard analysis indicated that in the presence of these antibodies, the
      affinity of the type I IGF receptor for insulin was comparable with that of the
      insulin receptor. These data indicate that regions both within and outside the
      cysteine-rich domain of the receptor alpha-subunit are important in determining
      the affinity and specificity of ligand binding. These antibodies promise to be
      valuable tools in resolving issues of IGF-I receptor heterogeneity and in
      studying the structure and function of classical type I receptors and insulin/IGF
      receptor hybrids.

PMID- 1377678
TI  - Peptidolytic monoclonal antibody elicited by a neuropeptide.
AB  - We report evidence that a monoclonal antibody raised by immunization with a
      vasoactive intestinal peptide (VIP)-carrier protein conjugate selectively
      hydrolyzes VIP and a fluorescence quenched decapeptide (FQ14-22D), representing
      the region of VIP most susceptible to autoantibody-mediated cleavage (residues 14
      22). A high affinity of the antibody for VIP and a lower affinity for FQ14-22D
      were revealed by kinetic studies and further substantiated by potent inhibition
      of FQ14-22D cleaving activity by full-length VIP. Sequencing of FQ14-22D
      hydrolysis products indicated selective cleavage at one peptide bond. These
      observations suggest that antibodies induced against naturally occurring
      polypeptide antigens can express peptidolytic activity targeted for specific
      sequences in the recognition epitope.

PMID- 1377677
TI  - Branched-chain alpha-ketoacid dehydrogenase kinase. Molecular cloning,
      expression, and sequence similarity with histidine protein kinases.
AB  - A cDNA for branched-chain alpha-ketoacid dehydrogenase kinase was cloned from a
      rat heart cDNA library. The cDNA had an open reading frame encoding a protein of
      382 amino acid residues with a calculated molecular weight of 43,280. The clone
      codes for the branched-chain alpha-ketoacid dehydrogenase kinase based on the
      following: 1) the deduced amino acid sequence contained the partial sequence of
      the kinase determined by direct sequencing; 2) expression of the cDNA in
      Escherichia coli resulted in synthesis of a 43,000-Da protein that was recognized
      specifically by kinase antibodies; and 3) enzyme activity that phosphorylated and
      inactivated the branched-chain alpha-ketoacid dehydrogenase complex was found in
      extracts of E. coli expressing the protein. Northern blot analysis indicated the
      mRNA for the branched-chain alpha-ketoacid dehydrogenase kinase was more abundant
      in rat heart than in rat liver, as expected from the relative amounts of kinase
      activity expressed in these tissues. The deduced sequence of the kinase aligned
      with a high degree of similarity within subdomains characteristic of procaryotic
      histidine protein kinases. This first mitochondrial protein kinase to be cloned
      appears more closely related in sequence to procaryotic histidine protein kinases
      than to eucaryotic serine/threonine protein kinases.

PMID- 1377679
TI  - Differential effects of W mutations on p145c-kit tyrosine kinase activity and
      substrate interaction.
AB  - The c-kit gene, mapped to the dominant white spotting (W) locus of the mouse
      (Chabot, B., Stephenson, D. A., Chapman, V. M., Besmer, P., and Bernstein, A.
      (1988) Nature 335, 88-89; Geissler, E. N., Ryan, M. A., and Housman, D. E. (1988)
      Cell 55, 185-192), encodes a receptor tyrosine kinase, p145c-kit. Germline
      mutations at the W locus lead to loss of function alterations in p145c-kit, and
      result in mice with developmental defects of varying severity in the melanocytic,
      hematopoietic stem cell, and primordial germ cell lineages. To investigate in
      more detail the effect of W mutations on p145c-kit signaling, three mutations,
      W42, Wv, and W41, that confer severe, intermediate, and mild phenotypic
      characteristics, respectively, were introduced into the human p145c-kit tyrosine
      kinase domain. These mutations attenuated the intrinsic tyrosine kinase activity
      of the receptor to different degrees. In addition, they had differential effects
      on the interaction of the p145c-kit substrates, phospholipase C gamma, GTPase
      activating protein, and the receptor-binding subunit of phosphatidylinositol 3'
      kinase, p85. Notably, the Wv mutation, while retaining significant receptor
      tyrosine kinase activity, was unable to bind phospholipase C gamma and GTPase
      activating protein, but could still associate with p85. These results suggest
      that the location of W mutations may be an important determinant of the
      specificity of substrate association and phosphorylation, and may explain, at
      least in part, the cell type-specific defects associated with certain W alleles.

PMID- 1377680
TI  - Molecular cloning of human mevalonate kinase and identification of a missense
      mutation in the genetic disease mevalonic aciduria.
AB  - Mevalonic aciduria is the first proposed inherited disorder of the
      cholesterol/isoprene biosynthetic pathway in humans, and it is presumed to be
      caused by a mutation in the gene coding for mevalonate kinase. To elucidate the
      molecular basis of this inherited disorder, a 2.0-kilobase human mevalonate
      kinase cDNA clone was isolated and sequenced. The 1188-base pair open reading
      frame coded for a 396-amino acid polypeptide with a deduced M(r) of 42,450. The
      predicted protein sequence displayed similarity to those of galactokinase and the
      yeast RAR1 protein, indicating that they may belong to a common gene family.
      Southern hybridization studies demonstrated that the mevalonate kinase gene is
      located on human chromosome 12 and is a single copy gene. No major rearrangements
      were detected in the mevalonic aciduria subject. The relative size (2 kilobases)
      and amounts of human mevalonate kinase mRNA were not changed in mevalonic
      aciduria fibroblasts. Approximately half of the mevalonic aciduria cDNA clones
      encoding mevalonate kinase contained a single base substitution (A to C) in the
      coding region at nucleotide 902 that changed an asparagine residue to a threonine
      residue. The presence of this missense mutation was confirmed by polymerase chain
      reaction amplification and allele-specific hybridization of the genomic DNAs from
      the proband and the proband's father and brother. Similar analysis failed to
      detect this mutation in the proband's mother, seven normal subjects, or four
      additional mevalonic aciduria subjects, indicating that the mutation does not
      represent a common gene polymorphism. Functional analysis of the defect by
      transient expression confirmed that the mutation produced an enzyme with
      diminished activity. Our data suggest that the index case is a compound
      heterozygote for a mutation in the mevalonate kinase gene.

PMID- 1377681
TI  - Inhibition of thyrotropin-induced DNA synthesis in thyroid follicular cells by
      microinjection of an antibody to the stimulatory G protein of adenylate cyclase,
      Gs.
AB  - Thyrotropin (TSH) is an important regulator of thyroid follicular cells. While
      its role in the maintenance of differentiated functions is undisputed, its role
      as a mitogen is less clear. TSH induces DNA synthesis and cell proliferation in
      some cells, while in others, TSH is mitogenic only in the presence of additional
      growth factors such as insulin-like growth factor-1. TSH causes elevations in
      intracellular cAMP and is thought to utilize this second messenger system in its
      mitogenic action. We studied TSH as a mitogen in Wistar rat thyroid cells (WRT)
      (Brandi, M. L., Rotella, C. M., Mavilia, C., Franceschelli, F., Tanini, A., and
      Toccafondi, R. (1987) Mol. Cell. Endocrinol. 54, 91-103) and examined the role of
      the guanine nucleotide binding protein, Gs, in its mitogenic action. WRT cells
      synthesized DNA in response to TSH and elevations in cAMP. In addition, TSH
      caused a rapid stimulation of an indicator gene whose expression is regulated by
      cAMP response elements. Following microinjection of an inhibitory polyclonal
      antibody raised against the Gs protein, both TSH-induced changes in gene
      expression and DNA synthesis were significantly reduced. These results
      demonstrate that virtually all of the mitogenic action of TSH is transduced
      through the Gs protein in WRT cells, presumably through the regulation of
      adenylate cyclase. Whether all or only part of TSH action is mediated by cAMP and
      the cAMP-dependent protein kinase remains to be determined.

PMID- 1377682
TI  - Antibodies to the carboxyl terminus of human apolipoprotein A-I. The putative
      cellular binding domain of high density lipoprotein 3 and carboxyl-terminal
      structural homology between apolipoproteins A-I and A-II.
AB  - We have studied the binding of 125I-labeled high density lipoproteins (HDL3) to
      liver plasma membranes, which are thought to contain specific HDL receptor sites,
      using anti-peptide antibodies directed against two sites in the carboxyl-terminal
      region of human apoA-I. Two distinct antibody populations raised to peptides
      corresponding to amino acid residues 205-220 and 230-243, respectively,
      recognized regions of apoA-I that are exposed in the lipid environment of HDL3.
      However, anti-AI[230-243] IgG, but not anti-AI[205-220] IgG, recognized HDL2,
      suggesting that residues 205-220 of apoA-I are expressed differently in the two
      HDL populations. In addition, anti-AI[230-243] IgG showed strong cross-reactivity
      toward apoA-II. Epitope mapping studies showed that anti-AI[230-243] binds to an
      epitope located in the carboxyl-terminus of apoA-II, demonstrating significant
      structural homology between the carboxyl-terminal of apoA-II, demonstrating
      significant structural homology between the carboxyl-terminal regions of apoA-I
      and A-II, two candidate proteins for mediating the specific cellular interaction
      of HDL3. Fab fragments from anti-AI[205-220] and anti-AI[230-243] inhibited the
      binding of 125I-HDL3 to liver plasma membranes by approximately 80% and 60%,
      respectively. These findings are in agreement with our recent work using isolated
      CNBr fragments of apoA-I (Morrison, J., Fidge, N. H., and Tozuka, M. (1991) J.
      Biol. Chem. 266, 18780-18785), which suggest that the carboxyl-terminal region of
      apoA-I contains a binding domain which mediates the specific interaction of HDL3
      with liver plasma membranes, possibly through the involvement of specific HDL
      receptors.

PMID- 1377683
TI  - Pig testicular 20 beta-hydroxysteroid dehydrogenase exhibits carbonyl reductase
      like structure and activity. cDNA cloning of pig testicular 20 beta
      hydroxysteroid dehydrogenase.
AB  - cDNA inserts encoding 20 beta-hydroxysteroid dehydrogenase (EC 1.1.1.53) were,
      for the first time, isolated and cloned from a pig testis cDNA library using
      synthetic oligonucleotides deduced from the partially determined amino acid
      sequences. The cDNA contains an open reading frame predicted to encode 289 amino
      acid residues. Surprisingly, it has 85% amino acid homology to human carbonyl
      reductase. The purified enzyme exhibited carbonyl reductase activity. Adenine
      rich sequence was located in the 3'-untranslated nine-rich sequence was located
      in the 3'-untranslated region, which may mean that the gene originates by
      retroposition. RNA transcripts of 1.3, 3, and 6 kilobases were detected in
      poly(A)+ RNA extracted from pig testis by Northern blot hybridization. The steady
      state level of the RNA species increased to a maximum in testes from 10-day-old
      pigs, but rapidly declined thereafter to the same levels found in testes of
      mature animals.

PMID- 1377684
TI  - Characterization of the adenovirus E3 protein that down-regulates the epidermal
      growth factor receptor. Evidence for intermolecular disulfide bonding and plasma
      membrane localization.
AB  - We have characterized the biosynthesis and processing of a 91 amino acid
      hydrophobic integral membrane protein encoded by human group C adenoviruses which
      down-regulates the EGF receptor (Carlin, C. R., Tollefson, A. E., Brady, H. A.,
      Hoffman, B. L., and Wold, W. S. M. (1989) Cell 57, 135-144). Previous studies
      have shown that two immunologically related proteins are produced in vivo, a 13.7
      kDa protein encoded by E3 message f and a 11.3-kDa protein derived from 13.7 kDa
      by proteolysis (Hoffman, B. L., Ullrich, A., Wold, W. S. M., and Carlin, C. R.
      (1990) Mol. Cell. Biol. 10, 5521-5524; Tollefson, A. E., Krajcsi, P., Yei, S.,
      Carlin, C. R., and Wold, W. S. M. (1990) J. Virol. 64, 794-801). We report here
      that the 13.7- and 11.3-kDa proteins form intermolecular disulfide bonds
      cotranslationally at Cys-31 and tend to migrate as high molecular weight
      aggregates under nonreducing conditions. Both proteins are also present at the
      cell surface, as evidenced by specific immunoprecipitation from intact monolayers
      enzymatically labeled with 125I. Moreover, an antiserum specific for a putative
      extracellular epitope recognizes the same viral proteins as antibodies directed
      against a C-terminal synthetic 15-mer. The 13.7- and 11.3-kDa proteins are
      detected at early time points during pulse-chase radiolabeling of infected cells,
      do not undergo any further changes in molecular weight, and focus at their
      predicted isoelectric points (7.4 and 7.2, respectively). Identical results are
      obtained in stable transfectants constitutively expressing only 13.7 and 11.3
      kDa, suggesting that biosynthesis and processing is not dependent on other viral
      proteins. These results have been incorporated into a computer-based model to
      predict the orientation of 13.7 and 11.3 kDa in the lipid bilayer. This model
      provides a basis for testing predictions regarding the topology of the viral
      proteins, as well as putative interactions with heterologous proteins in the
      microenvironment of the plasma membrane that cause down-regulation of the
      epidermal growth factor receptor.

PMID- 1377685
TI  - Cloning a rat meprin cDNA reveals the enzyme is a heterodimer.
AB  - The structure of the kidney microvillar membrane metallopeptidase meprin (EC
      3.4.24.18) from rats has been examined. Previously reported to be a homotetramer,
      we demonstrate that the enzyme is composed of two similar but distinct subunits
      through tryptic peptide mapping and the sequencing of peptides of the papain
      solubilized form of the enzyme. Two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis reveals that the native rat meprin tetramer is
      dissociated by detergent into disulfide-linked heterodimers. A full-length cDNA
      clone encoding one of the meprin subunits has been isolated and sequenced. The
      cDNA contains an open reading frame of 668 amino acids, coding for a polypeptide
      of molecular weight 75,054. The enzyme contains the zinc binding sequence HEFLH
      and a potential membrane-spanning region near its amino terminus. Comparison of
      this clone with peptide sequences from mouse meprins A and B shows that the clone
      is a B type or beta subunit. Northern blot analysis is consistent with the
      existence of two distinct subunits and further indicates that rat meprin subunits
      may be differentially expressed in various rat tissues.

PMID- 1377686
TI  - The human serglycin gene. Nucleotide sequence and methylation pattern in human
      promyelocytic leukemia HL-60 cells and T-lymphoblast Molt-4 cells.
AB  - The complete nucleotide sequence of the 16.7-kb human gene that encodes the
      peptide core (serglycin) of a secretory granule proteoglycan was determined, thus
      representing the first proteoglycan peptide core gene to be sequenced in its
      entirety. The exons, intron 1, and intron 2 comprised 7, 53, and 40% of the gene,
      respectively. Nineteen Alu-repetitive DNA sequences were interspersed in the
      gene, accounting for 28% of the total nucleotides in intron 1 and 40% of the
      nucleotides in intron 2. The nucleotide sequence was then used in an examination
      of the methylation pattern of the human serglycin gene in human promyelocytic
      leukemia HL-60 cells that contain serglycin mRNA and in T-lymphoblast Molt-4
      cells that do not. With polymerase chain reaction methodology, 13 DNA probes of
      250-880 base pairs in length were generated that corresponded to unique, non-Alu
      sequences spaced throughout the entire human serglycin gene. When blots
      containing genomic DNA digested with HpaII or MspI were examined with these
      genomic probes, it was discovered that the 5'-flanking region and intron 1 of the
      serglycin gene in HL-60 cells were both substantially less methylated than intron
      2. In contrast, the entire serglycin gene in Molt-4 cells was highly methylated.
      Because hypomethylated genes generally are transcribed more efficiently than
      hypermethylated genes, the high level of serglycin mRNA in HL-60 cells probably
      is a consequence of the low level of methylation of intron 1 and the 5'-flanking
      region of the serglycin gene in these cells.

PMID- 1377687
TI  - Vitronectin regulates the synthesis and localization of urokinase-type
      plasminogen activator in HT-1080 cells.
AB  - The effect of extracellular matrix composition on the location, amount, and
      activity of cell-associated urokinase-type plasminogen activator was tested using
      HT-1080 cells adherent to either fibronectin or vitronectin. Specific
      immunoprecipitation of newly synthesized urokinase indicated that cells adherent
      to fibronectin synthesized 2-3-fold more urokinase than cells adherent to
      vitronectin. Complexes of urokinase and plasminogen activator inhibitor type 1
      (PAI-1) were detected in cell layers of vitronectin-adherent but not fibronectin
      adherent cells. Inhibition of PAI-1 using a neutralizing monoclonal antibody
      resulted in a 3-fold increase in urokinase enzymatic activity on vitronectin
      adherent cells. Urokinase activity on fibronectin adherent cells was only
      slightly increased following PAI-1 neutralization. Examination of both HT-1080
      and normal human fibroblast cells by immunofluorescent microscopy localized
      urokinase-type plasminogen activator to discrete, focal areas underneath cells
      adherent to vitronectin. Urokinase was not detectable by immunofluorescence on
      cells adherent to fibronectin. The addition of exogenous prourokinase to locate
      urokinase receptors on adherent HT-1080 cells indicated that the focal
      localization of cell-surface urokinase resulted from the clustering of urokinase
      receptors following adhesion to vitronectin but not fibronectin-coated
      substrates. These results suggest that vitronectin can contribute to the control
      of cell-surface plasmin activity by regulating the synthesis of urokinase and
      directing the localization of urokinase receptors.

PMID- 1377688
TI  - Sequential translocation of an artificial precursor protein across the two
      mitochondrial membranes.
AB  - We have constructed a chimeric mitochondrial precursor protein consisting of a
      mutant bovine pancreatic trypsin inhibitor coupled to the C terminus of a
      purified artificial precursor protein. This construct fails to complete its
      import into isolated mitochondria and becomes stuck across sites of close contact
      between the two mitochondrial membranes. When the mitochondria are then depleted
      of ATP and the intramolecular disulfide bridges of the trypsin inhibitor are
      cleaved by dithiothreitol, the trypsin inhibitor moiety is transported across the
      outer membrane into the intermembrane space. This translocation intermediate can
      be chased across the inner membrane by restoring the ATP levels in the matrix.
      These results show that translocation of pancreatic trypsin inhibitor across a
      biological membrane is prevented by its intramolecular disulfide bridges, that
      import into the matrix involves two distinct translocation system operating in
      tandem, and that ATP is required for protein translocation across the inner but
      not the outer membrane.

PMID- 1377689
TI  - Spectrum of sialylated and nonsialylated fuco-oligosaccharides bound by the
      endothelial-leukocyte adhesion molecule E-selectin. Dependence of the
      carbohydrate binding activity on E-selectin density.
AB  - Carbohydrate recognition by the human endothelial-leukocyte adhesion molecule, E
      selectin, has been investigated by binding studies using 3H-labeled Chinese
      hamster ovary cells expressing different levels of the transfected full-length
      adhesion molecule and a series of structurally defined oligosaccharides linked to
      the lipid phosphatidylethanolamine dipalmitoate (neoglycolipids) and synthetic
      glycolipids chromatographed on silica gel plates or immobilized on plastic wells.
      Evidence is presented for density-dependent binding of the membrane-associated E
      selectin not only to 3'-sialyl-lacto-N-fucopentaose II (3'-S-LNFP-II) and 3'
      sialyl-lacto-N-fucopentaose III (3'-S-LNFP-III) which express the sialyl Le(a)
      and sialyl Le(x) antigens, respectively, but also to the nonsialylated analogue
      LNFP-II; there is a threshold density of E-selectin required for binding to these
      sialylated sequences, and binding to the nonsialylated analogue is a property
      only of cells with the highest density of E-selectin expression. The presence of
      fucose linked to subterminal rather than to an internal N-acetylglucosamine is
      shown to be a requirement for E-selectin binding, and although the presence of
      sialic acid 3-linked to the terminal galactose of the LNFP-II or LNFP-III
      sequences substantially enhances E-selectin binding, the presence of 6-linked
      sialic acid abolishes binding. E-selectin binding is unaffected in the presence
      of the blood group H fucose (alpha 1-2 linked to galactose to form the Le(b)
      antigen). However, the binding is abolished when in addition alpha 1-3-linked N
      acetylgalactosamine to the galactose (blood group A antigen) is present. These
      results indicate that some E-selectin-mediated adhesive events may be influenced
      by blood group status.

PMID- 1377690
TI  - The human complement regulatory protein CD59 binds to the alpha-chain of C8 and
      to the "b"domain of C9.
AB  - The erythrocyte membrane inhibitor of the human terminal complement proteins,
      surface antigen CD59, has previously been shown to enter into a detergent
      resistant complex with either the membrane-bound complex of C5b-8 or C5b-9 (Meri,
      S., Morgan, B. P., Davies, A., Daniels, R. H., Olavesen, M. G., Waldmann, H. and
      Lachmann, P. J. (1990) Immunology 71, 1-9; Rollins, S. A., Zhao, J., Ninomiya,
      H., and Sims, P. J. (1991) J. Immunol, 146, 2345-2351). In order to further
      define the interactions that underlie the complement-inhibitory function of CD59,
      we have examined the binding interactions between 125I-CD59 and the isolated
      components of human complement membrane attack complex, C5b6, C7, C8, and C9. By
      density gradient analysis, we were unable to detect interaction of 125I-CD59 with
      any of these isolated complement components in solution. Specific binding of 125I
      CD59 to C8 and C9 was detected when these human complement proteins were adsorbed
      to either plastic or to nitrocellulose, suggesting that a conformational change
      that accompanies surface adsorption exposes a CD59-binding site that is normally
      buried in these serum proteins. The binding of 125I-CD59 to plastic-adsorbed C8
      and C9 was saturable and competed by excess unlabeled CD59, with half-maximal
      binding observed at 125I-CD59 concentrations of 80 and 36 nM, respectively. No
      specific binding of 125I-CD59 was detected for surface-adsorbed human C5b6 or C7
      nor was such binding observed for C8 or C9 isolated from rabbit serum. Binding of
      CD59 to human C8 and C9 was not mediated by the phospholipid moiety of CD59,
      implying association by protein-protein interaction. In order to further define
      the binding sites for CD59, ligand blotting with 125I-CD59 was performed after
      separation of C8 into its noncovalently associated subunits (C8 alpha-gamma and
      C8 beta) and after alpha-thrombin digestion of C9. These experiments revealed
      specific and saturable binding of 125I-CD59 to C8 alpha-gamma subunit (half
      maximal binding at 75 nM), but not to C8 beta, and specific and saturable binding
      to the 37-kDa fragment (C9b) of thrombin-cleaved C9 (half-maximal binding at 35
      nM), but not to the 25-kDa C9a fragment. Partial reduction of C8 alpha-gamma
      revealed that only C8 alpha polypeptide exhibited affinity for CD59, and no
      specific binding to the C8 gamma chain was detected.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1377691
TI  - Na,K-ATPase extracellular surface probed with a monoclonal antibody that enhances
      ouabain binding.
AB  - The Na,K-stimulated ATPase is inhibited by extracellular cardiac glycosides,
      which bind to the enzyme's alpha subunit. We used a monoclonal antibody, VG4, as
      a probe of the extracellular surface. The antibody was specific for Na,K-ATPase
      and bound to intact cells. The epitope was mapped to the first extracellular loop
      (H1-H2) of alpha, using a combination of techniques including trypsinolysis, N
      terminal sequence of a fragment containing the determinant, and analysis of the
      effects of species-specific sequence differences. The antibody inhibited Na,K
      ATPase activity under certain circumstances, indicating that the H1-H2 loop
      participates in conformational changes that are transmitted to the active site.
      Mutations in the H1-H2 loop have been shown by others to affect ouabain affinity.
      Ouabain and the antibody acted synergistically to inhibit the enzyme, which
      seemingly supported the hypothesis that the H1-H2 loop is an essential part of
      the cardiac glycoside binding site. Direct measurements of the binding of
      [3H]ouabain, however, indicated that VG4 enhanced rather than inhibited binding,
      presumably by promoting favorable conformation changes. The data suggest the
      possibility that the cardiac glycoside binding site may be intramembrane rather
      than extracellular.

PMID- 1377692
TI  - Phylogenetic conservation of cysteine proteinases. Cloning and expression of a
      cDNA coding for human cathepsin S.
AB  - A 1.8-kilobase full-length cDNA of human cathepsin S, a lysosomal cysteine
      proteinase, has been isolated. The single long open reading frame encodes a
      polypeptide of 331 amino acids consisting of a 15-amino acid NH2-terminal signal
      peptide, a propeptide of 99 amino acids, and a mature polypeptide of 217 amino
      acids. The deduced amino acid sequence contains only one potential N
      glycosylation site located in the propeptide. The NH2-terminal amino acid
      sequence of the mature polypeptide was confirmed by sequencing cathepsin S
      purified from human spleen. The cDNA detects a 1.9-kilobase transcript in
      poly(A)+ RNA from human fibroblasts. Expression of human cathepsin S in
      transfected baby hamster kidney cells resulted in up to more than 300-fold
      cathepsin S activity as compared to untransfected controls. In the expressing
      baby hamster kidney cells, human cathepsin S is transported to the lysosomes via
      the mannose 6-phosphate receptor pathway as shown by density gradient
      centrifugation, immunofluorescence, and detection of the 37-kDa cathepsin S
      precursor in the medium in the presence of NH4Cl. The deduced amino acid sequence
      of human cathepsin S exhibits a substantial degree of similarity with other human
      cysteine proteinases and papain indicating that they have a common ancestral gene
      and are members of a gene family.

PMID- 1377693
TI  - Candida albicans growth studies: a hypothesis for the pathogenesis of Candida
      infections in burns.
AB  - The proteolytic environment in which Candida albicans exists strongly affects its
      virulence. To determine whether virulence might be related to C. albicans growth
      in different proteolytic environments, we measured renal fungal load in burned
      mice and found significantly greater Candida census in kidneys from mice that
      were challenged with a high proteinase-generating parent C. albicans (MY 1044)
      versus those that were challenged with its low proteinase-generating mutant (MY
      1049). In vitro, MY 1044 cells grew faster than MY 1049 cells in media that
      contained sera from burned mice as the only nitrogen source. Augmentation of
      media with proteinase or a mixture of amino acids increased growth of MY 1049
      cells, whereas augmentation with proteinase inhibitor decreased MY 1044 growth.
      In conclusion, in vitro growth of both the mutant and its parent strain was
      affected by the proteolytic environment in which they existed; thus, virulence
      differences for MY 1044 and MY 1049 could be due in part to growth differences
      between these two strains in different proteolytic environments. These results
      were combined with existing observations, and we proposed a theory for the
      pathogenesis of C. albicans in burns.

PMID- 1377694
TI  - Proline dithiocarbamate inhibits N-nitrosodiethylamine induced liver
      carcinogenesis.
AB  - A study was conducted to determine the toxicity of different dithiocarbamates and
      of disulfiram. In an experiment showing the cytotoxicity against murine spleen
      lymphocytes, proline dithiocarbamate (PDTC) and thioproline dithiocarbamate
      showed the lowest toxicity. Therefore one of them was selected and different
      doses of the hydrophilic PDTC were checked for their ability to affect the
      development of liver and oesophagus tumours induced in BD-6 rats by N
      nitrosodiethylamine (NDEA). Rats were injected i.p. with 80 mg/kg NDEA once
      weekly for 10 weeks. Administration of PDTC, 1 h before and 24 h after the
      carcinogen, markedly decreased the number of rats developing NDEA-induced
      hepatocellular carcinoma and liver haemangioendothelioma. A 59%-77% reduction in
      the incidence of liver tumours was found in the different groups when the
      carcinogen was administered in combination with the inhibitor. For least 40 weeks
      after the start of the experiment PDTC protected the liver from NDEA
      carcinogenesis and did not shift the tumour development to any other organ. PDTC
      did not significantly affect the weight gain of the experimental animals. We
      conclude that parenteral administration of PDTC seems to represent a promising
      approach in chemoprevention of liver carcinogenesis.

PMID- 1377697
TI  - Basolateral distribution of fibronectin matrix assembly sites on vascular
      endothelial monolayers is regulated by substratum fibronectin.
AB  - Endothelial cells exhibit binding sites for the amino terminus of fibronectin
      that participate in subendothelial fibronectin matrix assembly. These binding
      sites, termed matrix assembly sites, are localized on the basolateral surface of
      confluent endothelial monolayers (Kowalczyk et al. Blood, 75:2335, 1990). The
      present study investigates the role of cell-cell and cell-substratum interactions
      in the localization of matrix assembly sites to the basal surface of endothelial
      cells. Cells were cultured in Transwell culture inserts and matrix assembly sites
      were detected by binding assays using an iodinated 70 Kd amino-terminal
      fibronectin fragment. Integrity of intercellular junctions was monitored by
      measuring protein flux across Transwell filters. Time course experiments
      demonstrated that matrix assembly site expression on the basolateral cell surface
      preceded intercellular junction formation. Transfer of confluent monolayers to
      calcium-free medium resulted in the loss of junctions and in an increase in 125I
      70 kD binding from the apical medium. The increased 125I-70 kD binding resulted
      from increased access of 125I-70 kD to basolateral matrix assembly sites and not
      from the relocation of binding sites to the apical membrane. To determine the
      effect of matrix composition on matrix assembly site expression and localization,
      cells were seeded onto vitronectin- or fibronectin-coated substrates. Fibronectin
      increased the expression of matrix assembly sites on the apical surface within 24
      hours. By 48 hours, matrix assembly sites were located only on the basolateral
      surface. Vitronectin had no effect on the expression or localization of matrix
      assembly sites. These results indicate that the expression and localization of
      matrix assembly sites on the surface of vascular endothelial cells can be
      regulated by substratum fibronectin.

PMID- 1377695
TI  - Calcium channel blocker treatment of tumor cells induces alterations in the
      cytoskeleton, mobility of the integrin alpha IIb beta 3 and tumor-cell-induced
      platelet aggregation.
AB  - Calcium channel blockers of the phenylalkylamine (i.e. verapamil),
      benzothiazepine (i.e. diltiazem) and dihydropyridine (i.e. nifedipine) classes
      were evaluated for effects on the tumor cell/platelet interactions using Walker
      256 carcinosarcoma cells (W256 cells). When W256 cells were pretreated for 15 min
      with channel blockers at concentrations of 50-200 microM, macroscopic tumor-cell
      induced platelet aggregation was inhibited (order of potency; nifedipine greater
      than diltiazem much greater than verapamil). However, ultrastructural analysis
      revealed limited, focal platelet aggregates associated with tumor cell plasma
      membranes of verapamil- and diltiazem-treated cells. There was no evidence of
      platelet activation or platelet association with the tumor cell membrane in cells
      pretreated with nifedipine. Walker 256 cells possess the intergrin alpha IIb beta
      3. Tumor cell alpha IIb beta 3 was shown to mediate tumor cell/platelet
      interactions in vitro [Chopra et al. (1988) Cancer Res. 48:3787]. Patching and
      capping of surface alpha IIb beta 3 were inhibited by nifedipine greater than
      diltiazem much greater than verapamil. The degree of inhibition of alpha IIb beta
      3 receptor mobility parallels the inhibition of tumor-cell-induced platelet
      aggregation. W256 cells are characterized by a well-developed microfilament and
      intermediate filament network and by the absence of a distinct microtubular
      network. Calcium channel blockers had no effect on the low polymerization level
      of tubulin. However, they induced rearrangement of microfilament stress fibers.
      Intermediate filaments were also rearranged but to varying degrees. The order of
      effectiveness for alteration of intermediate filament organization was nifedipine
      greater than diltiazem while verapamil was ineffective. We propose that the
      previously reported inhibition of tumor cell/platelet interaction and tumor cell
      metastasis by calcium channel blockers [Honn et al. (1984) Clin Exp Metastasis
      1:61] is due not only to the effects of the Ca2+ channel blockers on platelets,
      but also to their effect on the tumor cell cytoskeleton resulting in an
      inhibition of the mobility and function of the alpha IIb beta 3 receptor.

PMID- 1377698
TI  - Developmental regulation of insulin-like growth factor binding protein
      production: studies in fetal, postnatal, and pregnant sheep.
AB  - To assess the roles of developmental factors in the regulation of sheep IGFBP
      production at the cellular level, we characterized and compared the IGFBPs
      released by fetal, postnatal, and maternal sheep skin fibroblasts in culture with
      those in fetal, postnatal, and maternal sheep plasma. Sheep fibroblasts produced
      seven IGFBPs: a 36.5-41 kDa protein induced in vitro by IGF-I, likely
      representing oIGFBP-3; a 28.5 kDa protein that reacted with antisera to human
      IGFBP-2, likely representing oIGFBP-2; 25 and 27 kDa proteins induced in fetal
      fibroblasts by IGF-I; a 22 kDa protein that was inhibited by IGF-I, likely
      representing oIGFBP-4; and 21 and 23 kDa proteins labelled only by IGF-II,
      suggesting their similarities to IGFBP-6. The developmental pattern of IGFBP
      production by sheep fibroblasts in culture was similar in several respects to
      that observed in sheep plasma. For example, relative amounts of the 21, 22, and
      28.5 kDa IGFBPs exceeded that of the 36.5-41 kDa protein in early fetal
      fibroblast conditioned media and in fetal plasma, while the relative
      concentrations of the 36.5-41 kDa protein increased markedly during the perinatal
      period. Sheep plasma differed, however, in two major respects from fibroblast
      conditioned media: First, fetal, and to a far lesser extent maternal, plasma
      contained a 200 kDa IGF-II-selective BP, likely to be the circulating form of the
      IGF-II receptor; and second, plasma, unlike conditioned media, contained a 26 kDa
      IGFBP, likely to be oIGFBP-1. The results of our studies suggest that the
      production and release of IGFBPs by isolated sheep fibroblasts is regulated by
      developmental factors operative under in vitro culture conditions. The
      differences in the relative levels of IGFBPs in conditioned media from fetal,
      postnatal, and maternal sheep fibroblasts resemble in several respects the
      differences in the relative concentrations of the various IGFBPs in fetal,
      postnatal, and maternal sheep plasma. Thus, sheep fibroblasts provide a useful
      though imperfect model system by which to examine the nutritional and hormonal
      regulation of sheep IGFBP production at various developmental stages.

PMID- 1377699
TI  - Production of granulocyte colony-stimulating factor and granulocyte/macrophage
      colony-stimulating factor after interleukin-1 stimulation of marrow stromal cell
      cultures from normal or aplastic anemia donors.
AB  - We have studied stromal cell function in naive or interleukin-1 (IL-1)-stimulated
      (100 pg/ml) long-term marrow cultures (LTC) from 12 normal donors and 21 patients
      with severe aplastic anemia (AA). Conditioned media (CM) from normal LTC
      contained levels of erythroid burst-promoting activity (BPA) and
      granulocyte/macrophage (GM) colony-stimulating activity (CSA) comparable to those
      previously described (Migliaccio et al., [1990] Blood, 75:305-312). The addition
      of IL-1 to these cultures increased the level of CSA and, specifically, of
      granulocyte colony-stimulating factor (G-CSF) released. Anti-GM-CSF antibody
      neutralized BPA and CSA in normal naive LTC CM but only the CSA in the CM from IL
      1-stimulated LTC. Since the concentrations of GM-CSF, as detected with a specific
      immunoassay, did not increase after IL-1 treatment, these data suggest that IL-1
      stimulated cultures contain an unidentified growth factor having BPA. CM from AA
      stromal cells contained levels of CSA comparable to those observed in normal
      stromal cell CM but had significantly lower levels of BPA. Neither anti-GM-CSF
      nor anti-IL-3 antibodies neutralized the BPA in AA stromal cell CM. This activity
      may be related to that found in the CM of IL-1-treated normal stromal cells. In
      nearly 50% of stromal cell cultures of AA patients, addition of IL-1 failed to
      increase the BPA, CSA, or G-CSF. The presence of an inhibitor in naive or IL-1
      treated AA stromal cell CM was excluded by adding the CM to IL-3-stimulated
      cultures. These findings suggest that G-CSF and GM-CSF genes are differentially
      regulated in the marrow microenvironment. Furthermore, a marrow microenvironment,
      deficient in BPA production and, in some cases, unresponsive to IL-1 could
      contribute to marrow failure in some patients with AA.

PMID- 1377700
TI  - Regulation of albumin expression in fetal rat hepatocytes cultured under
      proliferative conditions: role of epidermal growth factor and hormones.
AB  - Sustained production of plasma proteins, notably albumin, is a reliable indicator
      of the differentiated state of hepatocytes. In this work, we have developed a
      fetal hepatocyte culture system where studying the regulation of albumin
      expression in proliferating liver cells. Our results show that under
      proliferative conditions (i.e., in the presence of EGF) fetal hepatocytes
      maintain albumin production above control quiescent non-treated cells. Glucagon
      and noradrenaline have no effect on the proliferation induced by EGF in cultured
      fetal hepatocytes; however, they act synergistically with the growth factor,
      increasing intracellular albumin levels. The maximum response is obtained by
      treatment of cells with EGF and noradrenaline. The stimulatory noradrenergic
      effect is mimicked by agents that increase cyclic AMP levels (forskolin plus
      IBMX). However, vasopressin or phorbol esters have no effect on albumin
      production, neither alone nor in combination with EGF. Dexamethasone, which does
      not alter the proliferative induction of EGF, increases albumin content. This
      effect is independent of the proliferative status of the cells and is not
      enhanced by glucagon, noradrenaline, or cyclic AMP increasing agents. The
      hormonal changes observed in albumin production partially correlate with changes
      in mRNA levels. This is the first time that cyclic AMP increasing agents are
      shown to act synergistically with EGF, increasing the expression of this liver
      specific gene.

PMID- 1377696
TI  - Structure of the axonal surface recognition molecule neurofascin and its
      relationship to a neural subgroup of the immunoglobulin superfamily.
AB  - The chick axon-associated surface glycoprotein neurofascin is implicated in
      axonal growth and fasciculation as revealed by antibody perturbation experiments.
      Here we report the complete cDNA sequence of neurofascin. It is composed of four
      structural elements: At the NH2 terminus neurofascin contains six Ig-like motifs
      of the C2 subcategory followed by four fibronectin type III (FNIII)-related
      repeats. Between the FNIII-like repeats and the plasma membrane spanning region
      neurofascin contains a domain 75-amino acid residues-long rich in proline,
      alanine and threonine which might be the target of extensive O-linked
      glycosylation. A transmembrane segment is followed by a 113-amino acid residues
      long cytoplasmic domain. Sequence comparisons indicate that neurofascin is most
      closely related to chick Nr-CAM and forms with L1 (Ng-CAM) and Nr-CAM a subgroup
      within the vertebrate Ig superfamily. Sequencing of several overlapping cDNA
      probes reveals interesting heterogeneities throughout the neurofascin
      polypeptide. Genomic Southern blots analyzed with neurofascin cDNA clones suggest
      that neurofascin is encoded by a single gene and its pre-mRNA might be therefore
      alternatively spliced. Northern blot analysis with domain specific probes showed
      that neurofascin mRNAs of about 8.5 kb are expressed throughout development in
      embryonic brain but not in liver. Isolation of neurofascin by immunoaffinity
      chromatography results in several molecular mass components. To analyze their
      origin the amino-terminal sequences of several neurofascin components were
      determined. The NH2-terminal sequences of the 185, 160, and 110-135 kD components
      are all the same as the NH2 termini predicted by the cDNA sequence, whereas the
      other neurofascin components start with a sequence found in a putative
      alternatively spliced segment between the Ig- and FNIII-like part indicating that
      they are derived by proteolytic cleavage. A combination of enzymatic and chemical
      deglycosylation procedures and the analysis of peanut lectin binding reveals O-
      and N-linked carbohydrates on neurofascin components which might generate
      additional heterogeneity.

PMID- 1377701
TI  - Characterization of the human myeloid cell nuclear differentiation antigen:
      relationship to interferon-inducible proteins.
AB  - The human myeloid cell nuclear differentiation antigen (MNDA) is expressed
      specifically in cells of the granulocyte/monocyte lineage. The MNDA has been
      isolated by using a monoclonal antibody affinity matrix and reversed-phase high
      performance liquid chromatography. Its NH2-terminal sequence has been obtained,
      as well as additional sequence information derived from peptides produced by
      cyanogen bromide and SV8 protease cleavages. Meaningful similarities were
      observed in extended regions between the MNDA and the reported beta interferon
      inducible proteins, 202 and 204, from Ehrlich ascites mouse tumor cells. An
      amphipathic, basic alpha-helical region, showing no similarity to the 202 and 204
      proteins, exhibited close similarity to a region in the interferon response
      factor-2, a protein which binds the interferon stimulated response element. The
      relatively high number of S(T)PXX motifs present in the partial amino acid
      sequence of the MNDA, described herein, suggests that the MNDA binds DNA and is a
      transcription factor.

PMID- 1377702
TI  - Cloning and sequence determination of bovine insulin-like growth factor binding
      protein-2 (IGFBP-2): comparison of its structural and functional properties with
      IGFBP-1.
AB  - Insulin-like growth factor binding proteins (IGFBPs) are secreted by several cell
      types and can modify IGF actions. Mandin-Darby Bovine Kidney (MDBK) cells have
      been shown to secrete a 34,000 Da form of IGF binding protein whose N-terminal
      sequence is similar to a form of IGFBP purified from rat BRL-3A cells that has
      recently been named IGFBP-2. These studies report the complete amino acid
      sequence of bovine IGFBP-2 and compare its functional properties with human IGFBP
      1. The protein is 81% identical to rat IGFBP-2. When compared with both rat IGFBP
      2 and human IGFBP-1, the positions of all 18 cysteine residues are conserved.
      Similarly an RGD sequence is present near the carboxyl terminus in both proteins.
      IGFBP-2 has a higher affinity for IGF-II than for IGF-I and its affinity for both
      forms of IGF is greater than for human IGFBP-1. Like IGFBP-1 the protein can
      enhance the DNA synthesis response of porcine aortic smooth muscle cells to IGF
      I; however, IGFBP-2 was much less potent. The maximum potentiation of the IGF
      mediated mitogenic response that could be achieved was approximately 42% that of
      IGFBP-1. This potentiation is dependent upon a factor contained in platelet poor
      plasma and if this factor is omitted from the incubation medium, IGFBP-2 inhibits
      DNA synthesis. The purification of IGFBP-2 will allow more detailed comparisons
      to be made between it and other forms of IGFBPs in physiologic test systems.

PMID- 1377703
TI  - Identification of localized autoantibody epitopes in thyroid peroxidase.
AB  - Recent reports have disagreed on the nature of the autoantibody epitopes in
      thyroid peroxidase (TPO). We used immunoprecipitation of recombinant human TPO
      constructs to determine if localized autoantibody binding sites exist in this
      autoantigen. In vitro transcription and translation of TPO cDNA fragments yielded
      35S-labeled products consisting of either full-length protein (933 amino acids)
      or N-terminal peptides of 631, 455, and 120 amino acids. Immunoprecipitates
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      autoradiography revealed that the Hashimoto's sera consistently precipitated the
      full-length and the 631 amino acid products, but not the shorter N-terminal
      peptides. An additional construct resulting in a full-length TPO peptide with an
      internal deletion of amino acids 4-455 was also made, and this product was also
      precipitated by the Hashimoto's sera. A fusion protein consisting of maltose
      binding protein followed by amino acids 456-933 of human TPO was produced in
      Escherichia coli and subjected to Western blot analysis using the Hashimoto's
      sera. The Hashimoto's sera reacted with the MalTose binding protein TPO (MBP/TPO)
      fusion protein, but not a control fusion protein (MBP/LacZ alpha). Together,
      these results indicate the presence of localized autoantibody epitopes in the
      portion of the human TPO molecule from amino acids 456 to 933, with at least one
      binding site located between amino acids 456 and 631.

PMID- 1377704
TI  - Basal and regulated secretion of insulin-like growth factor binding proteins in
      osteoblast-like cells is cell line specific.
AB  - Local secretion of insulin-like growth factor binding proteins (IGFBPs) may
      modulate the effects of IGF-I and IGF-II on bone cell metabolism and
      proliferation. Several osteoblast-derived cell lines are currently used as
      interchangeable models to study IGFBP production, although it is unknown whether
      findings in one cell line can be extrapolated to another cell line or to normal
      human osteoblasts. In this study, we examined by Western ligand blotting both
      basal and regulated secretion of IGFBPs in vitro in 1) normal human osteoblast
      like (hOB) cells cultured from explants of human trabecular bone; 2) an SV40
      transformed hOB (HOBIT) cell line; and 3) several human (U-2, MG-63, TE-85) and
      rat (ROS 17/2.8 and UMR-106-01) osteosarcoma cell lines. Constitutively, hOB and
      HOBIT cells produced a similar pattern of IGFBPs, while all other cell lines
      produced their own unique pattern of IGFBPs. The two rat cell lines differed from
      the human cell lines as well as from each other. The response to hormonal
      stimulation also varied among the cell lines. Treatment of hOB and HOBIT cells
      with IGF-I resulted in a 2-fold increase in medium levels of IGFBP-3; IGF-I
      decreased levels of 24-kilodalton (kDa) IGFBP in hOB cell-conditioned medium. In
      addition, IGF-I markedly increased levels of the 29/32/34 kDa IGFBP triplet in U
      2 cells, but had little or no effect in the other human and rat osteosarcoma cell
      lines. PTH increased a 29-kDa IGFBP apparent only in UMR 106-01 cell-conditioned
      medium, whereas GH had no direct effect on IGFBP secretion in any of the
      osteoblast-like cells tested. We conclude that basal and regulated secretion of
      IGFBPs from osteoblast-like cells is cell-line specific. Spontaneously
      transformed human or rat osteoblast-like cells provide unique model systems to
      study features of distinct IGFBPs and their regulation; however, hOB cells and
      their derivatives may be more appropriate models for understanding the regulation
      of IGFs in human bone.

PMID- 1377705
TI  - Cytokine modulation of progesterone and estradiol secretion in cultures of
      luteinized human granulosa cells.
AB  - To clarify the possible roles of cytokines in the regulation of luteal cell
      function, we examined the effects of interferon (IFN), interleukin-1 (IL-1), and
      tumor necrosis factor (TNF) on progesterone and estradiol secretion in cultures
      of luteinized human granulosa cells. IFN gamma reduced hCG-stimulated
      progesterone secretion in a concentration-dependent manner; at its maximal
      inhibitory concentration (10 ng/mL), IFN gamma reduced progesterone secretion to
      20% of that in the hCG-stimulated controls. Whereas other IFN (alpha and beta)
      reproduced the inhibitory effect of IFN gamma, IL-1 and TNF had no effect on hCG
      stimulated progesterone secretion at concentrations of 1 and 10 ng/mL. IFN gamma
      also markedly reduced FSH-stimulated estradiol secretion. Unlike their effects on
      hCG-stimulated progesterone secretion, IL-1 and TNF reproduced the inhibitory
      effect of IFN gamma on FSH-stimulated estradiol secretion. IFN gamma
      significantly reduced both hCG- and FSH-stimulated cAMP generation in granulosa
      cells. IL-1 and TNF inhibited FSH-stimulated cAMP generation, but they did not
      inhibit hCG-stimulated cAMP generation. None of these cytokines reduced forskolin
      stimulated cAMP generation, thus suggesting that these cytokines affect steps
      proximal to cAMP generation without affecting cAMP generation itself. IFN gamma
      also reduced progesterone secretion in response to (Bu)2cAMP, suggesting that it
      also affects steps distal to cAMP generation. This study has demonstrated that
      cytokines modulate the steroidogenesis of luteinized human granulosa cells in
      vitro; the results suggest that cytokines may play permissive roles in regulating
      luteal cell function.

PMID- 1377706
TI  - Effects of recombinant human insulin-like growth factor-I (rhIGF-I) on total and
      free IGF-I concentrations, IGF-binding proteins, and glycemic response in humans.
AB  - To examine the effects of repeated administration of recombinant human insulin
      like growth factor-I (rhIGF-I) on IGF-I levels, free IGF-I pharmacokinetics,
      glycemic response, and IGF-binding proteins (IGFBP), we administered rhIGF-I
      (0.03 mg/kg iv bolus) to 12 healthy males each morning for 5 consecutive days.
      Serum was collected over 24 h on days 1 and 5 for measurement of total and free
      IGF-I, glucose, insulin, and IGFBP. Total IGF-I was measured by RIA after
      acid/ethanol extraction. Free IGF-I was separated from binding protein-complexed
      IGF-I using size exclusion high performance liquid chromatography before
      measurement by RIA. IGFBP were quantitated by optical densitometry of Western
      ligand blots. Total IGF-I increased significantly from 0-24 h after
      administration on day 1 (mean +/- SD, micrograms/L: 120 +/- 44 to 166 +/- 51, P =
      0.0002) but did not increase significantly from 24 h on day 1 to 0 h on day 5
      (166 +/- 51 to 178 +/- 62) or from 0-24 h on day 5 (178 +/- 62 to 209 +/- 89).
      The area under the total IGF-I concentration curve was greater on day 5 than day
      1 (311 +/- 99 min.g/L vs. 249 +/- 77, P = 0.0001). There were no significant
      differences in free IGF-I concentration or pharmacokinetic parameters or in the
      degree or timing of hypoglycemia between days 1 and 5. Plasma insulin levels
      decreased significantly following rhIGF-I administration (day 1 baseline: 53 +/-
      11 pmol/L, nadir: 18 +/- 6 pmol/L at 30 min, P = 0.003); day 5 baseline: 47 +/-
      15 pmol/L, nadir: 16 +/- 8 pmol/L at 30 min, P = 0.0003. Western ligand blotting
      revealed the transient appearance of a 30-kilodalton band which migrates in a
      manner similar to IGFBP-1. This band was undetectable at baseline, peaked between
      150 and 210 min after rhIGF-I administration, and diminished by 480-600 min. The
      response was similar on days 1 and 5. There were no substantial changes in the
      serum levels of any other IGFBP. In summary, repeated iv bolus administration of
      rhIGF-I increased the level of total circulating IGF-I without changing free IGF
      I disposition or glycemic response. A 30-kilodalton IGFBP band, most likely IGFBP
      1, appeared transiently following rhIGF-I administration, probably as a result of
      suppression of insulin levels. IGFBP-2, -3, and -4 were unaffected.

PMID- 1377707
TI  - Glycosylation changes in human chorionic gonadotropin and free alpha subunit as
      gestation progresses.
AB  - Carbohydrate is important to the structure, function, and circulatory survival of
      the glycoprotein hormones. Human CG (hCG) and the related free alpha-molecule of
      pregnancy contain four and two asparagine-linked oligosaccharides, respectively.
      The present study analyzes changes in the glycosylation patterns of hCG and free
      alpha in early vs. late gestation. Five volunteers provided 24-h urine samples,
      weekly, throughout their pregnancies. Extracts of early pregnancy (weeks 7-12)
      and late pregnancy (weeks 28-32) urines were pooled. Early and late samples from
      each patient were subjected to gel filtration to separate hCG and free alpha, and
      the populations thus obtained were analyzed by lectin affinity chromatography on
      Concanavalin A-Sepharose (Con A) and Lens culinaris-agarose (Lch). Using Con A,
      free alpha and hCG were separated into an unbound fraction (eluted with Con A
      buffer), a weakly bound fraction (eluted with 10 mmol alpha-methyl-D-glucoside)
      and a tightly bound fraction (eluted with 500 mmol alpha-methyl-D-mannoside). For
      free alpha-molecule, a significant decrease in tightly bound Con A forms, was
      noted from early to late pregnancy with a mean difference of 17.0 +/- 2.4% (P
      less than 0.01). Concomitantly, in late pregnancy, an increase in Con A unbound
      forms of free alpha was noted with mean difference of 12.5 +/- 1.7% (P less than
      0.01). These changes indicate the presence of more highly branched
      oligosaccharides on free alpha as gestation advances. No changes were noted in
      the Con A binding of intact hCG; nearly all hCG bound in both early and late
      pregnancy. Using Lch, free alpha and hCG were separated into an unbound fraction
      (eluted with Lch buffer) and a bound fraction (eluted with 500 mmol alpha-methyl
      D-mannose). Both free alpha and intact hCG in late pregnancy exhibited increased
      binding to Lch, with mean differences from early to late pregnancy of 30.2 +/-
      4.8% (P less than 0.01) and 11.4 +/- 4.5% (P less than 0.05), respectively. These
      data indicate increased incorporation of fucose into the carbohydrate moieties in
      late pregnancy. Taken together, these data derived by analysis using lectin
      specificity imply the presence of more highly branched, fucosylated
      oligosaccharides as gestation progresses.

PMID- 1377708
TI  - Multiple sclerosis: immunological findings and possible implications for therapy.

PMID- 1377709
TI  - Comparison of CNS homing pattern among murine TH cell lines responsive to myelin
      basic protein.
AB  - A myelin basic protein (MBP)-reactive TH cell line capable of inducing
      experimental allergic encephalomyelitis (EAE), and a MBP-reactive TH cell clone
      that does not cause EAE were labeled with a fluorescent vital dye, and
      transferred into naive syngeneic SJL/J mice. Animals were killed before the
      appearance of symptoms (3 and 4 days post-injection). Sections obtained from the
      spleen, spinal cord and brain of both groups of animals were examined by
      fluorescence microscopy to localize labeled TH cells. At all time points
      examined, the spleens of both groups contained innumerable labeled cells. The
      spinal cords and brains of animals that had received EAE-causing cells had a
      basal level of 20 labeled cells/cm2 at 3 days; this number increased rapidly to
      150 cells/cm2 in the spinal cord at 4 days. Perivascular infiltrates and small
      foci of astrogliosis were already apparent in this group 3 days after injection.
      The spinal cords and brains of animals that had received the non-EAE-causing TH
      cells contained 50 labeled cells/cm2 at 3 days. The density of these transferred
      cells, as compared to that of the EAE-causing cells, suggested that they have an
      unaltered CNS-homing capability. However, by 4 days, the number of non-EAE
      causing labeled cells had returned to near basal level. Our findings suggest that
      discrimination between disease and non-disease causing MBP-responsive TH cells
      occurs within the first 3 days following transfer, requires the presence in the
      CNS of a limited number of TH cells, and depends on yet unidentified TH cell
      factor(s).

PMID- 1377710
TI  - Suppression of experimental autoimmune encephalomyelitis by gallium nitrate.
AB  - We examined the effect of gallium (Ga) nitrate on the development of the
      development of experimental autoimmune encephalomyelitis (EAE). Weekly
      subcutaneous injections of 10-30 mg/kg prevented clinical signs as well as
      histopathological changes of EAE. The optimal timing of a single injection of Ga
      was 6 days after induction of EAE, with amelioration also apparent following a
      single injection on day 3 or 9 but not day 12. Ga administered in vivo suppressed
      myelin basic protein (MBP) and purified protein derivative-specific lymphocyte
      proliferative responses in vitro. Addition of Ga to MBP-specific T lymphocyte
      line cultures at various times after initiation of culture revealed that Ga
      exerts an effect at an early stage of cellular activation.

PMID- 1377711
TI  - Myelin proteolipid protein: minimum sequence requirements for active induction of
      autoimmune encephalomyelitis in SWR/J and SJL/J mice.
AB  - Proteolipid protein (PLP) is the major protein constituent of mammalian central
      nervous system myelin. We have previously identified two different PLP
      encephalitogenic T cell epitopes in two mouse strains. Murine PLP peptides 103
      116 YKTTICGKGLSATV and 139-151 HCLGKWLGHPDKF are encephalitogenic determinants in
      SWR/J (H-2q) and SJL/J (H-2s) mice, respectively. The purpose of the present
      study was to determine the minimum sequence requirements for each of these PLP
      encephalitogens. In SWR/J mice, at least two distinct overlapping peptides can
      induce experimental autoimmune encephalomyelitis (EAE). The eleven residue
      sequences PLP 105-115 TTICGKGLSAT and PLP 106-116 TICGKGLSATV are
      encephalitogenic in SWR/J mice, but PLP 106-115 TICGKGLSAT, the decapeptide
      indigenous to both sequences, is non-encephalitogenic. In contrast, the shortest
      PLP sequence capable of inducing EAE in SJL/J mice is the nonapeptide 141-149
      LGKWLGHPD. These data indicate that encephalitogenic determinants of PLP are
      short contiguous peptide sequences similar in length and diversity to those of
      MBP.

PMID- 1377712
TI  - Synthetic peptide specificity of anti-myelin basic protein from multiple
      sclerosis cerebrospinal fluid.
AB  - Human myelin basic protein (h-MBP) purified from central nervous system (CNS)
      myelin has a molecular mass of 18.5 kDa and 170 residues. Eighteen synthetic
      peptides ranging from 8 to 25 residues and covering the length of h-MBP were
      prepared by the Fmoc method. Antibodies to h-MBP (anti-MBP) were isolated and
      purified from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS)
      by two-step affinity chromatography. Purified anti-MBP was reacted with
      increasing amounts of h-MBP as well as each of the 18 synthetic peptides in an
      initial liquid phase assay, and then titers of free anti-MBP in the resulting
      mixtures were determined by a solid phase radioimmunoassay. Purified anti-MBP was
      neutralized by h-MBP and 6 of the 18 synthetic peptides used in this study. The
      antibody was completely neutralized by peptides No. 12 (residues: 80-97), No. 15
      (residues: 91-106) and No. 56 (residues: 75-95) and was partially neutralized by
      peptides No. 27 (residues: 61-75), No. 16 (residues: 64-78) and No. 21 (residues:
      69-83). The 12 remaining synthetic peptides covering both the amino (residues 1
      63) and carboxyl (residues 117-162) terminals of h-MBP did not neutralize
      purified anti-MBP. These results suggest that anti-MBP purified from CSF of
      patients with MS have affinity for discontinuous epitopes located between
      residues 61 and 106 on the h-MBP molecule. Alternatively anti-MBP may be
      polyspecific recognizing different amino acid sequences.

PMID- 1377713
TI  - Galanin immunoreactivity in the primate central nervous system.
AB  - Galanin-immunoreactive profiles were localized within the monkey and human
      central nervous system. In the monkey telencephalon, galanin-immunoreactive
      perikarya were seen within the anterior olfactory nucleus, basal forebrain,
      endopiriform nucleus, hippocampus, and bed nucleus of the stria terminalis. The
      caudate nucleus and putamen contained galanin-immunoreactive perikarya whereas
      the nucleus accumbens displayed only galanin-immunoreactive fibers. In the
      diencephalon, galanin-immunoreactive profiles were seen within the medial
      preoptic area, periventricular, suprachiasmatic, paraventricular, and arcuate
      nuclei as well as the lateral hypothalamic area. Within the thalamus, only
      galanin-immunoreactive fibers were seen within the midline paraventricular,
      reuniens, and rhomboid nuclei. In the mesencephalon, scattered galanin
      immunoreactive fibers were seen in the periaquaductal gray, ventral tegmental
      area, and midbrain reticular formation. In the metencephalon, galanin
      immunoreactive neurons were observed in the medial vestibular nucleus and nucleus
      prepositus. In the myelencephalon, galanin-immunoreactive perikarya were seen
      within the nucleus of the tractus solitarius and hypoglossal nucleus. Dense
      collections of galanin-immunoreactive fibers were found in the spinal descending
      tract of V, nucleus of the tractus solitarius, and dorsal motor nucleus of X.
      Galanin immunoreactivity was also observed within all circumventricular organs.
      Spinal anterior horn neurons expressed galanin immunoreactivity, and
      immunopositive fibers were seen within the tract of Lissauer and the substantia
      gelatinosa. Although the distribution of galanin immunoreactivity was generally
      similar between monkeys and humans, there were a few striking exceptions. The
      human supraoptic nucleus contained galanin-immunoreactive neurons, whereas the
      monkey supraoptic nucleus displayed only immunopositive fibers. Similarly,
      galanin-immunoreactive perikarya and fibers were seen in the human locus
      coeruleus and subcoeruleus, whereas in monkeys these regions contained only
      fibers. These data demonstrate a widespread distribution of galanin-containing
      profiles in primates, suggesting that galanin may modulate cognitive, sensory,
      motor, and autonomic processes.

PMID- 1377714
TI  - Substance P-immunoreactive sensory axons in the rat respiratory tract: a
      quantitative study of their distribution and role in neurogenic inflammation.
AB  - Substance P is one of the peptides released from sensory nerves that mediate
      "neurogenic inflammation." Although substance P-immunoreactive (SP-IR) axons are
      known to be present within the mucosa of the respiratory tract, the relative
      extent of the innervation of various components of the mucosa is not known.
      Therefore, we determined the distribution and number of SP-IR axons in the rat
      trachea and bronchi, by using immunohistochemistry on tissue whole mounts.
      Specifically, we sought to learn whether these axons directly innervate the
      postcapillary venules involved in neurogenic plasma extravasation, the arterioles
      involved in neurogenic vasodilatation, and the airway smooth muscle involved in
      bronchoconstriction in pathogen-free, adult male F344 rats. We found that 90% of
      the SP-IR axons were single axons, usually having varicosities. Eighty-five
      percent of these were in the epithelium, 6% innervated arterioles, and the
      remainder elsewhere in the lamina propria. Only 10% of the mediator-sensitive
      postcapillary venules (i.e., venules labeled with Monastral blue pigment after
      challenge with capsaicin or substance P) were within 10 microns of SP-IR axons.
      SP-IR axons were more than 10 times as frequent in the smooth muscle of the
      distal bronchi as in the trachea. Capsaicin pretreatment (168 mg/kg over 7 days)
      reduced the number of SP-IR axons in the trachea by 96%, which is consistent with
      their being sensory. Unilateral vagotomy reduced the number of SP-IR axons
      bilaterally in the trachea and ipsilaterally in the main stem bronchus. Using an
      antibody to Protein Gene Product 9.5 as a nonspecific marker for all nerves in
      the trachea, we determined that SP-IR axons constituted 90% of the axons in the
      epithelium, 32% of the axons on arterioles, and only 4% of the axons in the
      smooth muscle. We conclude that most SP-IR nerves in the trachea are sensory
      axons and most of these axons end in the epithelium. SP-IR axons innervate
      mucosal arterioles, but few innervate postcapillary venules. Therefore, the
      mechanism by which sensory axons evoke plasma extravasation from these venules is
      likely to involve the diffusion of the peptide or a secondary mediator from the
      epithelium or from the arterioles upstream.

PMID- 1377715
TI  - Co-localization of tyrosine hydroxylase, GABA and neuropeptide Y within axon
      terminals innervating the intermediate lobe of the frog Rana ridibunda.
AB  - Possible co-existence of gamma-aminobutyric acid (GABA), catecholamines, and
      neuropeptide Y (NPY) in the same nerve terminals of the frog intermediate lobe
      was investigated by immunocytochemistry at the electron microscopic level. Co
      localization of GABA and tyrosine hydroxylase (TH) was studied by using a double
      immunogold labeling procedure. Co-localization of glutamate decarboxylase (GAD)
      and NPY was studied by combining, respectively, the peroxidase-antiperoxidase
      method and a radioimmunocytochemical labeling procedure. Catecholamines and GABA
      were systematically co-localized in nerve endings of the pars intermedia. Most of
      the NPY-immunoreactive fibers also contained GAD-like immunoreactivity. However,
      a few NPY-positive nerve terminals were not immunoreactive for GAD. These data
      provide evidence for co-existence of a regulatory peptide (NPY) and several
      neurotransmitters (i.e., GABA and catecholamines) within the same axon terminals
      in the intermediate lobe. Since GABA, dopamine, and NPY have all been shown to
      inhibit the activity of frog melanotrope cells, the present findings suggest that
      these neuroendocrine factors may interact either at the pre-synaptic or post
      synaptic level.

PMID- 1377717
TI  - Patterns of antigenic expression in the thalamic reticular nucleus of developing
      rats.
AB  - The present study describes the development of the thalamic reticular nucleus in
      rats with the use of Nissl staining and antibodies to parvalbumin and pro-alpha
      thyrotropin-releasing hormone (alpha TRH). Two major subdivisions of the
      reticular nucleus are apparent: 1) the main body, which is itself heterogeneous
      and lies for the most part between the fibres of the internal capsule and
      external medullary lamina, and 2) the perireticular nucleus, which lies lateral
      to the main body and medial to the globus pallidus. In the main body of the
      reticular nucleus of adults, most cells in all regions are immunoreactive to
      parvalbumin and alpha TRH. During development there are two waves of parvalbumin
      and alpha TRH expression. The first wave occurs between postnatal day (P) 0 and
      P10, and labelled cells are apparent in rostrolateral areas of the main body of
      the nucleus only. At P10, such cells are not apparent. From P7 to adult, there is
      a second wave of parvalbumin and alpha TRH expression: labelled cells emerge
      first in central, then in caudal, and finally in rostral areas of the nucleus. In
      adults, the perireticular nucleus is made up of a few small cells which are
      immunostained for parvalbumin and alpha TRH. These cells are more frequent in
      areas of the internal capsule adjacent to the ventral regions of the main body of
      the reticular nucleus, rostrodorsal to the entopeduncular nucleus. From E
      (embryonic day) 17 to about P10, the perireticular nucleus consists of a
      surprisingly large population of neurones, many of which are parvalbumin and
      alpha TRH immunoreactive. By about P10, as in adults, there are few perireticular
      cells.

PMID- 1377716
TI  - Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of
      catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in
      the ventral tegmental area.
AB  - Physiological and pharmacological studies indicate that descending projections
      from the prefrontal cortex modulate dopaminergic transmission in the nucleus
      accumbens septi and ventral tegmental area. We investigated the ultrastructural
      bases for these interactions in rat by examining the synaptic associations
      between prefrontal cortical terminals labeled with anterograde markers (lesion
      induced degeneration or transport of Phaseolus vulgaris leucoagglutinin; PHA-L)
      and neuronal processes containing immunoreactivity for the catecholamine
      synthesizing enzyme, tyrosine hydroxylase. Prefrontal cortical terminals in the
      nucleus accumbens and ventral tegmental area contained clear, round vesicles and
      formed primarily asymmetric synapses on spines or small dendrites. In the ventral
      tegmental area, these terminals also formed asymmetric synapses on large
      dendrites and a few symmetric axodendritic synapses. In the nucleus accumbens
      septi, degenerating prefrontal cortical terminals synapsed on spiny dendrites
      which received convergent input from terminals containing peroxidase
      immunoreactivity for tyrosine hydroxylase, or from unlabeled terminals. In single
      sections, some tyrosine hydroxylase-labeled terminals formed thin and punctate
      symmetric synapses with dendritic shafts, or the heads and necks of spines. Close
      appositions, but not axo-axonic synapses, were frequently observed between
      degenerating prefrontal cortical afferents and tyrosine hydroxylase-labeled or
      unlabeled terminals. In the ventral tegmental area, prefrontal cortical terminals
      labeled with immunoperoxidase for PHA-L were in synaptic contact with dendrites
      containing immunogold reaction product for tyrosine hydroxylase, or with
      unlabeled dendrites. These results suggest that: (1) catecholaminergic (mainly
      dopaminergic) and prefrontal cortical terminals in the nucleus accumbens septi
      dually synapse on common spiny neurons; and (2) dopaminergic neurons in the
      ventral tegmental area receive monosynaptic input from prefrontal cortical
      afferents. This study provides the first ultrastructural basis for multiple sites
      of cellular interaction between prefrontal cortical efferents and mesolimbic
      dopaminergic neurons.

PMID- 1377719
TI  - Pigmented basal cell carcinoma: investigation of 70 cases.
AB  - BACKGROUND: Pigmented basal cell carcinoma (PBCC) is a clinical and histologic
      variant of BCC. OBJECTIVE: Our purpose was to identify the histologic subtypes of
      BCC that were most often associated with pigment and to determine whether this
      correlated with outcome after excision. METHODS: A series of PBCC was identified
      and the histologic subtype noted. Margins of all excisions were examined for
      residual tumor. These results were then compared with a series of nonpigmented
      BCCs. RESULTS: In a series of 1039 consecutive BCCs, 70 (6.7%) contained pigment.
      The histologic growth pattern most frequently associated with pigment was the
      nodular/micronodular pattern (12.4%) followed by the nodular (7.7%), superficial
      (7.2%), micronodular (4.0%), and the nodular/micronodular/infiltrative (3.4%)
      patterns. Margins were examined for evidence of residual tumor in the 40 cases
      that were excised. In only one case (2.5%) was the margin positive for tumor.
      This was statistically significant (p less than 0.05) compared with 388 excisions
      of nonpigmented BCCs with comparable growth patterns in which 69 (17.7%) showed
      positive margins. CONCLUSION: PBCC, as a clinical variant, is more frequently
      excised with adequate margins than are tumors of comparable histologic subtypes
      that do not contain pigment.

PMID- 1377718
TI  - Glucose metabolism in freshly isolated Muller glial cells from a mammalian
      retina.
AB  - Glucose metabolism was studied in isolated retinal Muller glial cells from the
      juvenile guinea pig. Cells, once enzymatically isolated and purified, were
      identified by morphological criteria, positive vimentin immunoreactivity, and
      histochemical staining for glycogen. Purified suspensions of Muller cells were
      obtained in quantities sufficient for biochemical analysis (approximately 2 x
      10(5)/pair of retinas) and light microscopic autoradiography. In bicarbonate
      buffered Ringer's medium containing 3H-2-deoxyglucose and no glucose, greater
      than or equal to 80% of the glucose analogue taken up intracellularly by Muller
      cells was phosphorylated to 3H-2-deoxyglucose-6-phosphate. In autoradiographs,
      this non-metabolized product provided visual evidence of glucose phosphorylation:
      the distribution of cell grains mirrored the morphology of individual Muller
      cells in situ. Exposure to the glycolytic inhibitor iodoacetate (500 microM)
      caused an 85% decrease in adenosine triphosphate (ATP) content; concomitantly, 3H
      2-deoxyglucose-6-phosphate decreased by 90% and paralleled a dramatic decrease of
      cell labelling in autoradiographs, while levels of 3H-2-deoxyglucose did not
      change. In the continual absence of glucose, glycogen content decreased with time
      and this decrease was slowed by 36% in the presence of iodoacetate. This
      indicated that, in control conditions, glycosyl units from glycogen sustain
      cellular metabolism, and hence 3H-2-deoxyglucose phosphorylation. 3H-2
      deoxyglucose-6-phosphate concentration was 43-fold less than that of ATP in the
      control conditions so that depletion of ATP during iodoacetic acid (IAA)-blocked
      glycolysis was not due to hexokinase activity. These results demonstrate that
      this preparation is adequate for quantitative studies of glucose metabolism at
      the cellular and molecular level in an important metabolic compartment of the
      mammalian retina.

PMID- 1377720
TI  - Muir-Torre syndrome.
AB  - Muir-Torre syndrome is characterized by multiple sebaceous tumors, various
      internal malignancies and an autosomal dominant inheritance. We herein report a
      typical case. The patient was a 69-year-old man with sebaceous adenomas, a
      keratoacanthoma, and actinic keratosis in addition to carcinomas of the prostate,
      colon, duodenum, and larynx. His family members also suffered from multiple
      cancers.

PMID- 1377721
TI  - Eruptive pruritic papular porokeratosis.
AB  - Three cases of an unusual variant of porokeratosis (Mibelli) were described.
      Patients with disseminated superficial porokeratosis for some years suddenly
      developed intensively pruritic erythematous papules. Skin biopsies revealed that
      these papules contained cornoid lamellae on their tops. Pruritic papules subsided
      in several months, leaving slightly hyperkeratotic brown annular lesions which
      were shown to contain typical cornoid lamellae histopathologically. This type of
      porokeratosis has not been reported in the literature.

PMID- 1377722
TI  - Primary systemic amyloidosis: a unique case complaining of diffuse eyelid
      swelling and conjunctival involvement.
AB  - A 52-year-old Japanese woman with the chief complaint of marked swelling of her
      upper eyelids and a mass over the bulbar conjunctiva is reported. She previously
      noticed frequent purpura after minimal trauma, which was resolved shortly after
      taking some ascorbic acid. Laboratory data showed Ig-G kappa type M-protein in
      the serum and kappa type Bence-Jones protein in the urine by
      immunoelectrophoresis. Systemic examination showed mild hepatosplenomegaly, 1st
      degree of AV block, and a mild increase in plasma cells in the bone marrow
      biopsy. Histologically, the whole dermis of the eyelid skin and conjunctiva was
      replaced by a large quantity of amorphous, eosinophilic substances, which were
      diffusely positive with Direct Fast Scarlet 4BS. Immunohistochemical staining was
      positive for anti-amyloid P component antibody. Typical amyloid fibrils were
      proved by electron microscopy. She was finally diagnosed as primary systemic
      amyloidosis with diffuse swollen eyelids and conjunctival mass, symptoms which in
      primary systemic amyloidosis are very rare.

PMID- 1377723
TI  - Molluscum contagiosum occurring in an epidermal cyst--report of 3 cases.
AB  - We present three unusual cases of molluscum contagiosum occurring in epidermal
      cysts. All of them are asymptomatic, elevated, oval nodules diagnosed clinically
      as epidermal inclusion cyst or prurigo nodularis. Histology showed true epidermal
      cysts containing molluscum bodies throughout the cyst wall and some type of
      laminated material within the cyst itself. The lesion, in all three cases
      developed in the pubic area of young adult men.

PMID- 1377724
TI  - An association of acanthosis nigricans and Crouzon syndrome.
AB  - An 11-year-old Japanese female having acanthosis nigricans associated with
      Crouzon syndrome is reported. Crouzon syndrome is a craniostenotic craniofacial
      malformation associated with premature closure of selective calvarial sutures,
      exophthalmos, maxillary hypoplasia, and a beak-shaped nose. It is an autosomal
      dominant inherited disorder. Crouzon syndrome is one of the syndromes which may
      be associated with acanthosis nigricans. The association of acanthosis nigricans
      with Crouzon syndrome is assumed to be a rare abnormality, although the true
      frequency is uncertain. We have reviewed the reported cases of acanthosis
      nigricans associated with Crouzon syndrome and characteristics were discussed.

PMID- 1377725
TI  - Epidermal keratinocytes of bullous pemphigoid express intercellular adhesion
      molecule-1 (ICAM-1).
AB  - Intercellular adhesion molecule-1 (ICAM-1) is the ligand for lymphocyte function
      associated antigen-1 (LFA-1), mediating the adhesion of lymphocytes to vascular
      endothelium. Keratinocytes are known to express ICAM-1 in some inflammatory
      dermatoses. Using an indirect immunofluorescence method, we examined the patterns
      of ICAM-1 and LFA-1 staining in bullous pemphigoid (BP) lesions and compared them
      to pemphigus vulgaris (PV) cases. ICAM-1 was expressed on the cell surface and in
      the cytoplasm of epidermal keratinocytes at the sites of erythematous and bullous
      lesions of BP. LFA-1 molecules were expressed on T cells at the basement membrane
      zone. In addition, HLA-DR-positive keratinocytes were observed in the basal
      layer. ICAM-1 was not, however, expressed on epidermal keratinocytes in
      uninvolved skin from BP patients, PV or normal control skin. It is known that
      ICAM-1 is expressed on keratinocytes at the site of lymphoid infiltration in
      cutaneous dermatoses and that LFA-1-positive T cells can bind to interferon gamma
      induced ICAM-1-positive keratinocytes. Our results suggest that cellular immunity
      involving ICAM-1 and LFA-1 may play a part in the pathogenesis of bullous
      pemphigoid.

PMID- 1377726
TI  - Cutaneous leiomyosarcoma.
AB  - A child's head-sized tumor on the upper back developed in a 43-year-old man. In
      spite of an extensive operation for the tumor, he died of multiple metastasis 15
      months after the operation. Histologically, tumor cells proliferated throughout
      the dermal and subcutaneous regions, and a boxed-in appearance was noted with
      silver staining. Because electron microscopic observations strongly suggested a
      smooth muscle origin, we diagnosed this case as cutaneous and subcutaneous
      leiomyosarcoma.

PMID- 1377727
TI  - Attention deficit disorder in reading-disabled twins: evidence for a genetic
      etiology.
AB  - In order to assess the genetic etiology of attention deficit hyperactivity
      disorder (ADHD), the basic regression model for the analysis of selected twin
      data (DeFries & Fulker, 1985, 1988) was fitted to questionnaire data (DICA:
      Diagnostic Interview for Children and Adolescents; Herjanic, Campbell, & Reich,
      1982) for 37 identical and 37 fraternal twin pairs tested in the Colorado Reading
      Project. Results of this analysis suggest that ADHD is highly heritable.
      Moreover, adjusting DICA scores for either IQ or reading performance differences
      did not substantially change parameter estimates. In future analyses of larger
      data sets, distinguishing between possible subtypes of attentional problems
      (e.g., ADD with or without hyperactivity) may facilitate tests of more searching
      etiological questions.

PMID- 1377728
TI  - Rostrocaudal differences in morphology and neurotransmitter content of cells in
      the subretrofacial vasomotor nucleus.
AB  - The rostral ventrolateral medulla (RVLM) contains sympathoexcitatory neurons that
      exert a powerful control over the sympathetic outflow to the cardiovascular
      system. In the cat there is a concentration of such neurons (but not neurons
      subserving other functions) within a narrow longitudinal column in the RVLM
      termed the subretrofacial (SRF) nucleus. Furthermore, it has been suggested that
      there are subgroups of cells, located at different rostrocaudal levels of the SRF
      nucleus, that preferentially or exclusively control different vascular beds (e.g.
      in the kidney and hindlimb). The aim of this study was to map quantitatively the
      rostrocaudal distribution within the nucleus of different cell types, defined
      according to morphological and/or chemical criteria, and to correlate this with
      the regional vasomotor effects (in hindlimb and kidney) evoked by stimulation of
      SRF cells at the corresponding rostrocaudal levels. SRF cells were highly
      heterogeneous with respect to both their morphology and chemical properties. They
      varied greatly in size (equivalent diameter ranging from 10-40 microns) as well
      as in shape and orientation. An immunohistochemical examination using the avidin
      biotin procedure revealed that many SRF cells (estimated 57% of all SRF cells)
      were immunoreactive for tyrosine hydroxylase (TH, a marker of catecholamine
      cells). In addition, there were SRF cells immunoreactive for neuropeptide Y (NPY,
      11% of total), enkephalin (ENK, 16% of total), and serotonin (5HT, 10% of total),
      but not for substance P, galanin or somatostatin. Different cell types, defined
      according to their morphology and/or chemical properties, were unevenly
      distributed throughout the nucleus. In the most caudal part of the SRF nucleus,
      virtually all cells were TH-positive, and the large majority (estimated 80%) were
      NPY-positive, suggesting that many cells at this level contained both TH and NPY.
      In contrast, in the most rostral part of the SRF nucleus, only 30% of cells were
      TH-positive, and no NPY-positive cells were observed. Both 5HT- and ENK-positive
      cells were found throughout the rostrocaudal extent of the nucleus, but
      predominantly within its rostral part. Furthermore, TH-positive cells in the
      rostral SRF nucleus were on average significantly larger (mean equivalent
      diameter 18-43% greater) than TH/NPY-positive cells in the caudal part of the
      nucleus, but smaller than 5HT- or ENK-positive cells at the same level. Overall,
      rostral cells (regardless of their chemical type) were larger than caudal cells
      within the SRF nucleus (mean equivalent diameter 13-28% greater).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1377729
TI  - Interaction of putative neurotransmitters in rostral ventrolateral medullary
      cardiovascular neurons.
AB  - As recent immunohistochemical evidence has shown the coexistence of putative
      neurotransmitters in the rostral ventrolateral medulla (RVLM), we have
      investigated the possibility that there may be an interaction of putative
      transmitters on the firing frequency of cardiovascular neurons in the RVLM.
      Extracellular activity was recorded from 37 spontaneously firing units in the
      right RVLM of urethane anaesthetized and artificially ventilated rats. Nine of
      these units were classified as cardiovascular neurons because: (i) they were
      silenced by baroreceptor activation (1-3 micrograms phenylephrine i.v.); and (ii)
      they showed rhythmicity of their spontaneous activity in synchrony with the
      cardiac cycle. Microiontophoresis of combinations of near threshold amounts of L
      glutamate (GLU; 10 nA), acetylcholine (Ach; 30 nA) and substance-P (SP; 60 nA)
      showed a synergistic interaction of these substances with one another in
      eliciting changes in firing frequency of cardiovascular neurons. These results
      show that GLU and Ach, GLU and SP and Ach and SP interact synergistically to
      influence the firing frequency of cardiovascular neurons in the RVLM and suggest
      that these substances play a physiological role in the neural control of the
      circulation.

PMID- 1377730
TI  - Nervous control of the release of substance P and neurokinin A from the isolated
      perfused porcine ileum.
AB  - Using isolated perfused porcine ileum we studied the release of substance P (SP)
      and neurokinin A (NKA) in response to electrical stimulation of the mixed
      periarterial nerves and to infusion of different neuroactive agents. Nerve
      stimulation (8 Hz) had no significant effect on the release of SP and NKA. Nerve
      stimulation also had no effect on the release of SP and NKA during infusion of
      atropine (10(-6) M) or phentolamine (10(-5) M), whereas a significant increase
      (from 8.2 +/- 1.9 to 20.1 +/- 4.6 pmol/l for SP and from 12.3 +/- 2.7 to 34.2 +/-
      7.7 pmol/l for NKA, n = 7) was observed during nerve stimulation after
      pretreatment with both atropine and phentolamine. This increase was abolished by
      hexamethonium (3 x 10(-5) M). Also acetylcholine infusion causes a significant
      release of SP and NKA after infusion of both atropine and phentolamine (to 172 +/
      56% and 232 +/- 69% of basal release, n = 7), an effect that was abolished by
      hexamethonium infusion. Infusion of atropine alone increased the release of SP
      and NKA significantly (to 337 +/- 92% and 386 +/- 124% of basal output, n = 5).
      Norepinephrine (10(-6) M) inhibited the release of SP and NKA (to 69 +/- 6% and
      80 +/- 6% of basal release, n = 7). Our results suggest that the SP- and NKA
      producing neurons receive intrinsic tonic muscarinic inhibitory impulses,
      extrinsic nicotinic excitatory impulses, and extrinsic adrenergic inhibitory
      impulses.

PMID- 1377731
TI  - Role of vitamin A in the haematotoxicity of hexachlorocyclohexane (HCH) in the
      rat.
AB  - The haematotoxicity of technical hexachlorocyclohexane (HCH) (1000 ppm) was
      investigated in male albino rats fed with diet free of vitamin A or containing
      vitamin A at 2000 or 10(5) I.U./kg. Assessment of HCH-induced haematotoxicity at
      the end of the 7 weeks feeding period was done on the basis of haemoglobin
      content, total count of red blood cells and white blood cells and the
      differential counts of the white blood cells as well as by parameters such as
      packed cell volume, mean corpuscular volume, mean corpuscular haemoglobin, mean
      corpuscular haemoglobin content, prothrombin time and clotting time. In the rats
      fed with vitamin A-free diet containing HCH, significant reductions were noticed
      in the total white blood cells count, clotting time and prothrombin time
      indicating severe haematotoxicity. Differential count of the white blood cells of
      these rats revealed a non-significant reduction in the lymphocyte count. The only
      indication of haematotoxicity caused by hexachlorocyclohexane in the vitamin A
      supplemented rats was a slight but statistically significant reduction of the
      total count of white blood cells. These results demonstrate that the
      haematotoxicity of hexachlorocyclohexane in the rats is enhanced by vitamin A
      deficiency and its supplementation particularly in excess but not at
      hypervitaminotic level is protective against the toxicity.

PMID- 1377732
TI  - Simultaneous immunostaining method for localization of bromodeoxyuridine and
      calcitonin gene-related peptide.
AB  - A new simultaneous double immunostaining method has been optimized to localize
      the DNA synthesis marker bromodeoxyuridine (BrdU) and calcitonin gene-related
      peptide (CGRP) in endocrine cells of Bouin's-fixed, paraffin-embedded rat lung.
      Nuclease pre-treatment before immunostaining is compatible with optimal tissue
      morphology and CGRP antigenicity preservation. Nickel-enhanced development of
      avidin-biotin-peroxidase staining is used to show CGRP immunoreactivity in black
      and alkaline phosphatase-anti-alkaline phosphatase is applied to demonstrate
      incorporated BrdU in red. The present methodology could be useful for studies
      requiring detection of incorporated BrdU in cells producing regulatory peptides
      or other labile antigens.

PMID- 1377733
TI  - Immunohistochemical study of basement membrane reconstruction by an epidermis
      dermis recombination experiment using cultured chick embryonic skin: induction of
      tenascin.
AB  - The production of extracellular matrix components such as laminin, Type IV
      collagen, fibronectin, and tenascin during the formation of basement membrane in
      cultured epidermis-dermis recombinant skin of 13-day-old chick embryo was
      analyzed immunohistochemically. The epidermis and dermis were separated from each
      other by treatment with EDTA and/or dispase. The basal lamina of the basement
      membrane was thus removed from both epidermis and dermis. The isolated epidermis
      was overlaid onto the isolated dermis, i.e., recombined, and then cultured for 1
      7 days in a chemically defined medium (BGJb) on a Millipore filter.
      Immunofluorescence labeling was used for light microscopy and HRP or colloidal
      gold labeling for electron microscopy. In specimens from 2-day cultures, positive
      sites of anti-laminin and anti-fibronectin reaction were observed light
      microscopically as patches which, at the electron microscopic level, corresponded
      to fragments of the basal lamina located immediately beneath and in the vicinity
      of the attachment plaques of the hemidesmosomes. The staining pattern became
      continuous 7 days after recombination. Fluorescence labeling of laminin and
      fibronectin appeared somewhat earlier than that of Type IV collagen and tenascin.
      All of the four components were found localized primarily in the basal lamina.
      Furthermore, fibronectin and tenascin were also distributed in the extracellular
      matrix of the dermis. The expression of tenascin, which does not exist in the
      basement membrane of 13-day-old intact embryonic skin, was induced in vitro.
      These results suggest that hemidesmosomes may play an important role in the
      reconstruction of the basement membrane and that various components of the
      basement membrane appeared at different times during the reconstruction.

PMID- 1377734
TI  - [3H]-adenine metabolism and radiation damage during in vitro development of the
      kidney.
AB  - We followed the early post-induction changes in nucleic acid synthesis of the
      metanephric kidney anlage in vitro. Enhanced incorporation of [3H]-thymidine and
      [3H]-adenine was detected, but several factors were shown to influence the
      interpretation of such in vitro experiments. The incorporation is dependent not
      only on the stage of development of the target organ but also on its transfer to
      organ culture, as early rudiments require an "adaptive" pre-cultivation to
      stabilize their metabolism; at more advanced stages growth and DNA synthesis
      proceed without delay. Another potential artifact is radiation damage which is
      caused by the incorporated radioisotope and can be detected in prolonged
      cultures. A [3H]-adenine pulse of more than 1 microCi/ml for 2 hr leads to
      definite growth retardation, and a 10-microCi/ml pulse causes extensive cell
      death and atrophy on a 4- to 6-day subculture. The radiation damage is dose
      dependent and of variable severity in the different cell lineages within the
      organ. Since the radioisotope doses were in the range of those commonly used for
      monitoring cell proliferation and metabolism, we stress the risk of obtaining
      artifactual results, especially in prolonged cultures after pulse-labeling.

PMID- 1377735
TI  - Differential extractability of calcium and pectic substances in different wall
      regions of epicotyl cells in young flax plants.
AB  - We applied the simultaneous use of a subtractive method and two imaging
      techniques (secondary ion mass spectrometry and electron microscopy after PATAg
      staining) to correlate the distribution of Ca2+ to pectic substances in cell
      walls of young flax plants. The calcium images were compared with the structural
      electron microscopy images. This suggests that the linkage of the pectic
      substances within the wall is mainly by calcium bridges in the intercellular
      junctions of most types of cells under study (epidermis, subepidermis, fiber
      layer, and endodermis) and in the outer part (close to the cuticle) of the wall
      of the epidermal cells. In the primary walls of the various types of cells under
      study and in the inner part (close to the cytoplasm) of the wall of the epidermal
      cells, the linkage of the pectic substances would be mainly by covalent bonds. In
      the middle lamellae of the various cells, and in the intercellular junctions
      within the cortical parenchyma, both types of linkages apparently coexist. The
      mechanism of "ionic condensation" may provide an interpretation for the chemical
      status of the Ca2+ ions which are associated with the pectic components
      solubilized in boiling water, and which do not seem to contribute to the linkage
      of these components within the wall.

PMID- 1377736
TI  - Distribution of the extracellular matrix proteins tenascin, fibronectin, and
      vitronectin in fetal, infant, and adult human spleens.
AB  - Using immunohistochemistry, we investigated the distribution of the extracellular
      matrix (ECM) glycoproteins tenascin, fibronectin, and vitronectin in fetal [16-24
      gestational weeks (GW)], infant (40 GW), and adult human spleens to clarify the
      presence of these proteins during different phases of maturation. In the red and
      white pulp, tenascin and fibronectin were constant components of the reticular
      fibers from the age of 18 GW onwards, whereas vitronectin was seen only in adult
      spleens. The immunohistochemical staining patterns of tenascin and fibronectin
      remained unchanged at different fetal ages. Ring fibers, which are modified
      basement membranes around venous sinuses, became visible relatively late, and in
      adult spleens they contained both tenascin and vitronectin but lacked
      fibronectin. The composition of the ring fibers is therefore clearly different
      from that of ordinary basement membranes, which have not been reported to contain
      tenascin or vitronectin. The rapidly increasing number of reticular fibers in the
      spleen at the age of approximately 18 GW corresponds with the beginning of
      lymphatic colonization. Reticular fibers, rich in ECM glycoproteins, form a
      framework to which cells can migrate and attach. We suggest that the composition
      of these fibers might be important for lymphatic colonization and function of the
      spleen.

PMID- 1377737
TI  - Novel method for performing carbonic anhydrase histochemistry and
      immunocytochemistry on cryosections.
AB  - It is difficult to correlate structure with function in the kidney because of the
      extensive cell heterogeneity. Carbonic anhydrase (CA) is an enzyme that mediates
      renal acidification and is found predominantly in proximal tubule and collecting
      duct cells. We modified Hansson's method for histochemically identifying cellular
      CA activity on PLP-fixed rabbit kidney sections mounted on Millipore filters, and
      then removed the filters to perform peanut lectin and antibody labeling on the
      same sections. There was adequate preservation of morphology, and individual
      cells could be identified with CA activity in the cytosol and specific antibody
      or lectin labeling on the cell surfaces.

PMID- 1377738
TI  - [Cellular characteristics of yolk sac tumor].
AB  - Morphological analysis of imprint cytology and histology was performed in 5
      patients with yolk sac tumor (YST). The age of the patients ranged from 14 to 37.
      The level of AFP ranged from 460 ng/ml to 13,464 ng/ml. Five patients had a
      primary lesion in the ovary. These five cases of YST were histologically
      evaluated and classified into 4 patterns. As a result, the endodermal sinus
      pattern was the most frequently identified, followed by the polyvesicular
      vitelline pattern. As with imprint cytology findings in 4 YST cases, cuboidal
      cells were the most frequently observed; cuboidal cells and nuclei were both
      cuboidal in shape and 25-40 mu and 20-25 mu in diameter respectively. The
      chromatin had fine to coarse granular patterns. The nuclear.cytoplasmic (N/C)
      ratio was 50-70%, and each nucleus contained one to four nucleoli. Next to
      cuboidal cells, spindle-shaped cells were most frequently noticed; 20-40 mu in
      size with spindle-shaped nuclei 10-20 mu in diameter and had a fine to coarse
      granular chromatin pattern. The nuclei of the 30-50% N/C ratio cells contained
      one to two nucleoli. Naked cells and bizarred cells were also noticed.

PMID- 1377739
TI  - ECG of the month. On a lower level. Hypokalemia.

PMID- 1377740
TI  - Sulfated glycoconjugates demonstrated in combination with high iron diamine
      thiocarbohydrazide-silver proteinate and silver acetate physical development.
AB  - Sulfated glycoconjugates in epithelial cells and mesenchymal cells were
      investigated after staining with high iron diamine-thiocarbohydrazide-silver
      proteinate. One purpose of the experiment was to apply a new physical developed
      to the staining. Instead of silver nitrate, silver lactate or silver bromide, we
      used silver acetate as an ion donor. This new method allowed physical development
      under normal lighting conditions, and resulted in the reduction of background
      staining even after amplification. As the developer did not contain gum arabic,
      troublesome treatment was not necessary. The time required for staining was very
      short and the electron density of the final reaction product was high and easily
      identifiable under the electron microscope. Fixing was not necessary. Very small
      amounts of reactive substance were detectable after physical development. This
      developmental procedure has been applied to both the preembedding staining and
      postembedding staining of sulfated glycoconjugates. The results obtained using
      this method are presented.

PMID- 1377741
TI  - One-year follow-up on the safety and efficacy of isoprinosine for human
      immunodeficiency virus infection. Scandinavian Isoprinosine Study Group.
AB  - The safety and clinical impact of isoprinosine in HIV-infected individuals were
      assessed in a multicentre, randomized, double-blind, 24-week study phase,
      followed by an optional 24-week open treatment phase. The results of the double
      blind phase have been reported. Of 866 HIV-seropositive patients randomized, 832
      subjects were eligible for efficacy analysis. On completion of the double-blind
      phase, 596 patients started open treatment. All patients were evaluated with
      regard to progression to AIDS and/or death. Within 48 weeks, 10/412 (2.4%)
      patients assigned isoprinosine and 27/420 (6.4%) patients assigned placebo
      progressed to AIDS (P = 0.005). Intention-to-treat analysis showed identical
      results. Viewing the open treatment phase in isolation revealed no difference in
      progression rates between those treated and those not receiving the drug, perhaps
      reflecting the higher proportion of patients receiving zidovudine or PCP
      prophylaxis in the latter group. No severe adverse reactions or toxicities were
      observed. We conclude that HIV-seropositive patients without AIDS may be safely
      and effectively treated with isoprinosine.

PMID- 1377743
TI  - Poster presentations as a strategy for evaluating nursing students in a research
      course.

PMID- 1377742
TI  - Hyperamylasemia following cardiopulmonary bypass.
AB  - In order to study the occurrence of postbypass hyperamylasemia, 75 patients
      undergoing cardiopulmonary bypass (CPB) were studied from March 1989 to January
      1990. There were 49 males and 26 females. Among them, 27 had congenital heart
      disease, 30 had valvular disease, and 18 had coronary artery disease. There were
      27 patients with at least one elevated serum amylase sample after operation.
      Thus, the overall incidence of hyperamylasemia was 36%. As compared with the
      preoperative data (1.3%), there was a statistically significant difference in the
      occurrence of hyperamylasemia (p less than 0.05). Three patients had overt
      clinical pancreatitis postoperatively. There was no positive correlation between
      the serum amylase level and the occurrence of pancreatitis (p greater than 0.05).
      Forty-two cases had a significant elevation of the amylase creatinine clearance
      ratio (ACCR) after CPB. However, there was no significant difference between the
      groups with pulsatile and nonpulsatile CPB (p greater than 0.05). Three patients
      (4%) died in our series. The causes of death were heart failure in two and
      fulminant pancreatitis associated with low cardiac output in one. Although our
      experience in dealing with pancreatitis improved survival, mortality was still
      high (33.3%) in our series. Nevertheless, there was no apparent correlation
      between mortality and postbypass hyperamylasemia (p greater than 0.05). Logistic
      regression analysis was used to analyze the risk factors of the occurrence of
      hyperamylasemia, and the analysis revealed that patients with coronary artery
      disease were susceptible to postbypass hyperamylasemia. Our studies indicate that
      the use of total serum amylase or ACCR to monitor for the occurrence of
      pancreatitis in postbypass patients is inadequate.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1377744
TI  - Taurine and serine supplementation modulates the metabolic response to tumor
      necrosis factor alpha in rats fed a low protein diet.
AB  - Plasma taurine and serine decrease following trauma and in severe inflammatory
      disease. These changes may signify an increase in requirements for sulfur amino
      acids. We previously demonstrated that cysteine supplementation can restore the
      impaired ability of rats fed an 8% casein diet to increase hepatic zinc,
      glutathione (GSH) and protein concentrations in response to tumor necrosis factor
      alpha (TNF alpha). Here we examined whether serine or taurine produces a similar
      effect, because serine provides the carbon skeleton of cysteine and taurine is
      its major metabolite. After 7 d of receiving either a 20% casein diet
      supplemented with cysteine or an 8% casein diet supplemented with alanine, serine
      or taurine, rats received an intraperitoneal injection of human TNF alpha. Tumor
      necrosis factor caused no change in hepatic GSH but resulted in a lower GSH
      concentration in lung in rats fed the alanine-supplemented diet. Neither taurine
      nor serine increased liver GSH relative to that in rats fed alanine, but the
      depression in lung due to TNF injection was lessened. The absolute increase in
      ceruloplasmin in response to TNF was enhanced in rats fed the alanine
      supplemented diet relative to those fed the 20% casein diet. Serine normalized
      this response. This observation--the effects of taurine and serine on lung GSH
      and a significant negative correlation between ceruloplasmin and liver and lung
      GSH concentration in rats fed TNF--suggests that supplemental serine and taurine
      may improve antioxidant defenses when dietary supplies of cysteine are low but do
      not influence cysteine availability for a normal response to TNF.

PMID- 1377745
TI  - Raw soybeans stimulate human pancreatic proteinase secretion.
AB  - Intraduodenal instillation of raw soybeans stimulated pancreatic proteinase
      secretion in humans. Raw soybeans almost abolished the activity of chymotrypsin
      and severely reduced (50%) the tryptic activity. Immunoreactive tryptic and
      chymotryptic material simultaneously appeared in amounts 2 to 4 times basal
      concentrations. This increase, demonstrated with rocket immunoelectrophoresis,
      was begun within the first 10 min of soybean instillation. The enhanced secretion
      also persisted throughout the succeeding saline instillation, and it is suggested
      that the presence of Kunitz trypsin inhibitor contributed to this postprandial
      stimulation. An amidase that hydrolyzes low-molecular-weight substrates (i.e.,
      benzoyl-arginine p-nitroanilide) was found in raw soybeans. Its low activity was
      not assumed to substantially bias standard trypsin assays. The increased
      proteinase secretion was, as previously published, not preceded by an elevated
      plasma cholecystokinin concentration. The raw soybeans also caused a nonparallel
      secretion of amylase and proteinases. Nervous, perhaps cholinergic, regulation
      mediates the inhibitor-stimulated proteinase secretion in humans. This
      stimulation yields both a general increase of proteinases and also a specific
      inhibitor-resistant trypsin. This is consistent with the physiologic need for
      proenzyme-activation in the presence of inhibitors and for restoration of the
      proteolytic capacity of the duodenal juice.

PMID- 1377746
TI  - Gastric and pancreatic enzyme activities and their relationship with some gut
      regulatory peptides during postnatal development and weaning in calves.
AB  - Changes in the activities of three gastric and nine pancreatic enzymes plus
      colipase were determined during postnatal development and weaning in calves. In
      calves exclusively milk-fed for 2, 7, 28, 56, 70 and 119 d, the enzyme activities
      per kilogram of empty live weight increased with age for chymotrypsin, elastase,
      carboxypeptidases A and B, ribonuclease and alpha-amylase, decreased for
      chymosin, lysozyme and colipase but showed no change in the case of pepsin,
      trypsin, lipase and phospholipase A2 compared with animals at birth. The greatest
      increase was that in alpha-amylase activity (about 50-fold between d 2 and 119).
      In calves weaned between d 28 and 56, all the activities were higher than in milk
      fed animals, except that of chymosin (which was slightly lower) and that of
      colipase (which did not change). At 119 d of age, chymotrypsin, carboxypeptidase
      A, alpha-amylase and lipase were 1.6- to fourfold higher in ruminants than in
      preruminants. Thus, most enzyme activities were modified first by colostrum and
      milk intake, and again upon weaning by development of the forestomachs and
      ingestion of solid food. These ontogenic patterns might be under the control of
      many gut regulatory peptides, the plasma concentrations of which changed
      simultaneously. Some gastric and pancreatic enzymes were correlated to plasma
      concentrations of these gut regulatory peptides.

PMID- 1377747
TI  - Effect of sexual steroid hormones on spiramycin disposition in genital tract
      secretions of the ewe.
AB  - The present work investigated the influence of sexual steroid compounds
      (estradiol 17 beta and fluorogestone) on antibiotic passage across the uterine
      barrier. Five healthy and mature ewes, with controlled hormonal impregnation,
      were given a single iv injection of spiramycin, a macrolide antibiotic, at a dose
      of 64,000 IU/kg. Plasma and uterine secretions were regularly sampled before the
      injection and for 30 h post-injection. Blood was collected from the jugular vein
      and uterine secretions were obtained by uterine flushing with a sterile saline
      solution containing 0.2% inulin. Spiramycin was concentrated in the uterine
      secretions, whatever the hormonal status; the secretions-to-plasma ratio was 4.68
      +/- 1.88 under estrogen priming and 2.68 +/- 0.91 under progestagen priming. The
      area under the concentration-time curve (AUC) and the mean residence time (MRT)
      were significantly higher (p less than 0.001) in uterine secretions than in
      plasma. The AUC in uterine secretions was significantly higher (p less than 0.05)
      under estrogen priming (439.07 +/- 241.25 IU.h/mL) than under progestagen priming
      (141.41 +/- 89.37 IU.h/mL). The spiramycin MRTs in uterine secretions were 11.92
      +/- 4.08 and 12.06 +/- 3.35 h for both estrogens and progestagen treatment,
      respectively. These experiments demonstrate that estrogens increase uterine
      bioavailability, but not the residence time, of spiramycin when administered by a
      systemic route.

PMID- 1377748
TI  - Synthesis of 3-[(2,3-dihydro-1,1,3-trioxo-1,2-benzisothiazol-2-yl)alkyl] 1,4
      dihydropyridine-3,5-dicarboxylate derivatives as calcium channel modulators.
AB  - 1,4-Dihydropyridine (DHP) derivatives with a 1,2-benzisothiazol-3-one 1,1-dioxide
      group, linked through an alkylene bridge to the C-3 carboxylate of the DHP ring,
      with both vasoconstricting and vasorelaxant properties were obtained. In blocking
      Ca(2+)-evoked contractions of K(+)-depolarized rabbit aortic strips, compounds 12
      and 41 were 10-fold more potent than nifedipine; 27 other compounds were 1-4-fold
      more potent. Their vascular versus cardiac selectivity was very pronounced; for
      instance, the selectivity index for compound 41 was 70-fold higher than that of
      nifedipine. This was also true for the vasoconstricting compound 22, which was as
      potent as Bay K 8644 in enhancing the Ca(2+)-evoked contractions of rabbit aorta
      strips, yet it had poor inotropic activity in rabbit left atria. Oral
      administration of compounds 38, 40, 43, and 53 (20 mg/kg) caused a 35-37%
      decrease in systolic blood pressure in spontaneously hypertensive rats (SHR);
      these effects were similar to those of nifedipine. However, iv administration of
      these compounds to anesthetized SHR caused a decrease in blood pressure which was
      more pronounced and long-lasting than that of nifedipine. When administered iv at
      100 micrograms/kg, the vasoconstricting compound 22 caused a 40% increase in
      systolic and diastolic blood pressure. Compound 22 exhibited an unusually
      interesting feature over the other five Ca2+ DHP agonists: it had diester
      substitutions at the C-3 and C-5 positions of the DHP ring. Overall, compounds
      possessing these properties might be useful in treating clinical cardiovascular
      conditions in which DHP Ca2+ antagonists or agonists are indicated.

PMID- 1377749
TI  - NMR studies of an FK-506 analog, [U-13C]ascomycin, bound to FK-506-binding
      protein.
AB  - Multidimensional, heteronuclear NMR methods were used to determine the complete
      1H and 13C resonance assignments for [U-13C]ascomycin bound to recombinant FKBP,
      including stereospecific assignment of all 22 methylene protons. The conformation
      of ascomycin was then determined from an analysis of NOEs observed in a 13C
      edited 3D HMQC-NOESY spectrum of the [U-13C]ascomycin/FKBP. This structure is
      found to be quite different from the solution structure of the two forms of
      uncomplexed FK-506. However, it is very similar to the X-ray crystal structure of
      FK-506 bound to FKBP, rms deviation = 0.56 A. The methods used for resonance
      assignment and structure calculation are presented in detail. Furthermore,
      FKBP/ascomycin NOEs are reported which help define the structure of the ascomycin
      binding pocket. This structural information obtained in solution was compared to
      the recently described X-ray crystal structure of the FKBP/FK-506 complex.

PMID- 1377750
TI  - Linkage of autosomal dominant dystrophic epidermolysis bullosa in three British
      families to the marker D3S2 close to the COL7A1 locus.
AB  - Linkage of the anonymous marker D3S2 at 3p21 has been shown in three British
      families with dominant dystrophic epidermolysis bullosa with a combined lod score
      of 6.75 at theta = 0. This locus is close to the collagen type VII locus implying
      that abnormalities of this gene cause dominant dystrophic epidermolysis bullosa.

PMID- 1377751
TI  - Preferential interaction of human immunodeficiency virus reverse transcriptase
      with two regions of primer tRNA(Lys) as evidenced by footprinting studies and
      inhibition with synthetic oligoribonucleotides.
AB  - Primer tRNA regions involved in the interactions between human immunodeficiency
      virus reverse transcriptase (HIV RT) and tRNA(Lys) were studied by digestion of
      primer with pancreatic ribonuclease in the presence or absence of HIV RT. The
      acceptor stem of tRNA(Lys) is not noticeably protected against nuclease action in
      the presence of HIV RT, while this enzyme clearly protects part of the anticodon
      and dihydrouridine loops of tRNA(Lys). The acceptor stem of primer tRNA was
      digested by RNase A only in the presence of the retroviral enzyme, suggesting a
      partial destabilization of this region by the HIV RT. Synthetic
      oligoribonucleotides, corresponding to the anticodon and the dihydrouridine
      loops, inhibited strongly reverse transcription, confirming the strong
      interaction of these tRNA regions with the enzyme.

PMID- 1377752
TI  - Impairment of helper T-cell function following severe head injury.
AB  - Major infections, such as sepsis and pneumonia, occur in 50-75% of patients
      following isolated severe head injury. Previous studies have demonstrated that
      this high incidence of infection following severe head injury may be related to a
      decrease in helper T-cell activation and function. The present study was designed
      to investigate the effect of severe head injury on specific subgroups of helper T
      cells known to enhance or suppress cellular immune function. Specifically,
      peripheral blood lymphocytes (PBLs) from 10 head-injured patients and 10 matched
      controls were evaluated following in vitro stimulation with the T-cell mitogen,
      phytohemagglutinin (PHA). Subsets of helper T cells evaluated included activated
      helper (CD4+/CD25+) T cells; helper/inducer (CD4+/CDw29+) T cells, which enhance
      cellular immune activity; and suppressor/inducer (CD4+/CD45R+) T-cells, which
      induce suppressor (CD8+) T-cells. In addition, the effect of intraventricular
      fluid (IVF) on PHA-stimulated in vitro CD4 and CD25 expression was investigated
      to determine whether severe head injury results in the production of mediators
      within the central nervous system capable of affecting T-cell activation. The
      results of this study indicate that isolated severe head injury selectively
      reduces the ability of PHA-stimulated PBLs to express the helper/inducer
      (CD4+/CDw29+) T-cell (p = 0.023) and activated helper (CD4+/CD25+) T-cell (P =
      0.041) phenotypes. There was no significant change in PHA-stimulated CD4 or CD25
      expression following incubation of PBLs with intraventricular fluid (IVF) from
      head-injured patients. The relationship between these changes in specific helper
      T-cell subpopulations and the infectious complications of severe head injury are
      discussed.

PMID- 1377753
TI  - Dextran-coupled deferoxamine improves outcome in a murine model of head injury.
AB  - Tissue damage involving oxygen-derived free radicals may be greatly exacerbated
      by free, reactive iron, which acts as a catalyst in oxidative reactions. The
      effects of free iron can be attenuated by the administration of deferoxamine
      (DFO), an iron chelator. However, DFO has limited therapeutic utility because it
      has a short plasma half-life (approximately 5.5 min in mice) and produces
      profound hypotension upon intravenous infusion. These negative attributes have
      been circumvented by the covalent attachment of DFO to large polymers, such as
      dextran or hydroxyethyl starch. The ability of the dextran-conjugated DFO (DEX
      DFO) to inhibit iron-catalyzed reactions with lipids was compared to that of the
      native molecule in an in vitro model of CNS lipid degradation in the presence of
      200 microM ferrous iron. There was no difference between native DFO and the
      modified form. Modified and unmodified DFO were also compared for therapeutic
      efficacy in a murine model of head injury. Using a previously described "grip
      test" as a measure of neurologic impairment following injury, DEX-DFO, native
      DFO, and dextran were administered intravenously 3-5 min after injury. Dextran
      DFO significantly decreased the incidence of severe neurologic impairment at
      dosage levels of 0.1 (n = 92), 1.0 (n = 76), and 10.0 (n = 80) mg/kg.
      Administration of native DFO or dextran had no effect at the same dosages and
      concentrations. These results suggest that the murine model of head injury
      contains a significant iron-dependent component that should be assessed in other
      models of neural injury.

PMID- 1377754
TI  - The effects of normovolemic hemodilution with dextran-40 on acute myocardial
      ischemia/reperfusion injury in rabbits.
AB  - The effects of decreasing blood viscosity by normovolemic hemodilution with
      dextran-40 or normal saline (NS) on myocardial lipid peroxides, superoxide
      dismutase, infarct size and left ventricular function during acute myocardial
      ischemia/reperfusion were studied in rabbits. It was found that normovolemic
      hemodilution with dextran-40 could decrease the content of ischemic myocardial
      malondialdehyde and preserve ischemic myocardial superoxide dismutase activity
      after 1 h of coronary occlusion followed by 1 h of reperfusion. However, after
      administration of NS only a tendency in this aspect exhibited without statistical
      significance. Besides, hemodilution with dextran-40 reduced infarct size and
      improved left ventricular systolic function after 1 h of ischemia followed by 23
      h of reperfusion. These results suggest that normovolemic hemodilution with
      dextran-40 may have anti-injury effect on acute myocardial ischemia/reperfusion
      to a certain degree.

PMID- 1377755
TI  - Simultaneous existence of galactose-containing glycoprotein and several
      neuropeptides in DRG of the rat.
AB  - By use of light microscopic immunohistochemical and lectin histochemical methods,
      the interrelation of galactose-containing glycoprotein (GCGP), calcitonin gene
      related peptide (CGRP)-like, leu-enkephalin (L-ENK)-like, and substance P (SP)
      like peptides has been evaluated on consecutive sections of dorsal root ganglia
      from colchicine-treated rats. The results showed that GCGP, CGRP, L-ENK and SP
      exist simultaneously in individual neurons of the dorsal root ganglia in rats.
      Almost all small neurons in dorsal root ganglion contained both GCGP and CGRP.
      The stronger peanut lectin affinity with small neurons, the weaker CGRP
      immunoreactivity, and vice versa. Some neurons of medium size were of strong CGRP
      like immunoreactivity; however, they lacked in affinity with peanut lectin. The
      large spinal ganglionic cells rarely showed CGRP immunoreactivity and affinity
      with peanut lectin. The results suggested that there was a negative interrelation
      between GCGP and CGRP in small primary sensory neurons. From the above it may be
      suggested that the GCGP plays an important role in recognizing and transmitting
      information in primary sensory neurons.

PMID- 1377756
TI  - Analysis of antigenic polypeptides of Dane particles and antibody response
      ability of HBV infected subjects to PreS1 polypeptides.
AB  - We demonstrated the constitutive polypeptides (PP) of Dane particles employing
      Western Blot and investigated the antibody response ability of HBV infected
      subjects to PreS1 PP in comparison with other serum markers from HBV infected
      individuals. The results indicated that 1) the major reason for discrepant
      results may be related to the detergents used in the sample solutions and the
      degree of denaturation the samples had undergone; 2) there are 12 bands in the
      PAGE-graph of Dane particles. By Western Blot it was confirmed that 5 PP (P24,
      P27, P36, P39, P42) are derived from S-open reading frame (S-ORF), P21 is
      associated with C-ORF, P24-25 possesses some epitopes of Pol protein, and P45 and
      P76 express similar epitopes to human IgG and IgM; and 3) the prevalence of anti
      PreS1 PP was 17.24% in the group of healthy persons following latent HBV
      infection, much higher than that of HBV infected patients (1.21%). The above
      findings imply that antibody response ability of the host to PreS1 PP is
      attributing to the outcome of HBV infection. It may play an important role in the
      elimination of the virus.

PMID- 1377757
TI  - Evaluation of efficacy of four pediculicides against head louse (Pediculus
      capitis) infestation.
AB  - To evaluate the efficacy and to determine the minimum effective dosage of four
      pediculicides against head louse infestation, as well as to select a safe,
      effective, practical, and cheap agent, 1,657 infested school children in 25
      primary schools in Szu-Hu, Kou-Hu, and Ku-Keng Districts of Yunlin County were
      treated and 1,611 of them were examined. The overall cure rate was 73% and the
      rate for boys (84%) was higher than that for girls (71%). The cure rate of Nix
      (permethrin 1%) cream rinse was 81%. The cure rate for single dosages of 1, 2, 3
      and 4 cases/tube (56 gm/tube) was 87%, 83%, 81% and 71%, respectively. The cure
      rate of Para aerosol (bioallethrine 0.66%) was 78%. The cure rate for single
      dosages of 30 and 40 cases/tube (90 gm/tube) was 87% and 70%, respectively. The
      cure rate of Prioderm (malathion 1%) cream shampoo was 64%. The cure rate for
      single dosages of 10, 15 and 20 cases/tube (40 gm/tube) was 74%, 71% and 52%,
      respectively. The cure rate of Delice (1% gamma benzene hexachloride) was 71%.
      The cure rate for single dosages of 5 and 10 ml/case was 64% and 76%,
      respectively. Of the 226 infested girls, 181 (80%) were found to be infested with
      1-10 head lice, 33 (15%) with 11-50 lice, 7(3%) with 51-100 lice and 5 (2%) with
      over 100 lice. Of the 2,160 head lice collected, 1,788 (83%) were nymphs, 284
      (13%) females, and 88 (4%) males. The mean number of head lice in each infested
      girl was 10 (range 1-137). The low cure rates obtained in the present study may
      be due to the fact that many school girl & have long hair. In comparison, Nix had
      the highest cure rate (81%) but the highest price (NT$ 120/case). The cure rate
      and price of Para aerosol (78%, NT$ 7.2/case) and Delice (71%, NT$ 16.7/case)
      came next. Prioderm (64%, NT$ 10.0/case) had the lowest rate and a slight
      offensive smell. Preliminary trials show that based on the cost-effectiveness,
      Para aerosol is best in head louse infestation control.

PMID- 1377758
TI  - Latent prostatic carcinomas found at autopsy in men over 90 years old.
AB  - Step-sections of 29 whole prostate glands obtained at autopsy from elderly men
      aged 90 years or over have been investigated. Latent prostatic carcinomas were
      found in 17 cases (58.6%), all in the peripheral region. The majority of these
      latent prostatic carcinomas in very old individuals were considered to correspond
      to stage A1 tumors since, in 75% of cases, the diameter was less than 1 cm.
      Benign nodular hyperplasia and atypical hyperplasia were also observed in 26
      (89.7%) and 14 cases (48.3%), respectively. There was a clear correlation between
      the appearance of atypical hyperplasia and the presence of latent prostatic
      carcinoma.

PMID- 1377759
TI  - Use of nucleolar organizer regions in the histopathological diagnosis of
      colorectal epithelial neoplasia.
AB  - The AgNOR technique, specific staining for nucleolar organizer regions, was
      applied to twenty-seven lesions (sixteen tubular adenomas with low grade atypia
      and eleven well-differentiated adenocarcinomas invading the submucosa) of
      colorectal epithelial neoplasia, to examine the possibility of its application to
      histopathological diagnosis. The mean AgNOR number per adenoma nucleus (2.62 +/-
      0.16) was significantly higher (P less than 0.01) than that per carcinoma nucleus
      (2.28 +/- 0.25). The mean cross-sectional area and the maximum diameter of
      carcinoma AgNORs (1.91 +/- 0.20 micron2 and 1.89 +/- 0.09 micron, respectively)
      were significantly larger than those of adenoma (1.15 +/- 0.17 and 1.45 +/- 0.11,
      respectively). The result of the discriminant analysis using these two variants
      corresponded to the pathological diagnosis with an accuracy of 96.3% (26/27). We
      thus concluded the AgNOR technique to be one of use in the histopathological
      diagnosis of colorectal epithelial neoplasia.

PMID- 1377760
TI  - [Effects of pH on the formation and dissociation of the complex of trypsin and
      PSTI].
AB  - The effects of pH on the formation and dissociation of the complex of trypsin and
      PSTI was investigated using pancreatic juice of two patients. Pancreatic juice
      was eluted from a Sephadex G100 column with the buffer in different pH values,
      and the trypsin inhibitory activity in the eluate was measured. Under alkaline
      and neutral conditions, the complex of PSTI and trypsin was observed, while in
      acidic condition, dissociation of the complex was occurred. Molar ratio of PSTI
      and trypsin in the complex was found to be one mole/one mole. Human serum, alpha
      1-antitrypsin, and alpha 2-macroglobulin dissociated the complex of PSTI and
      trypsin.

PMID- 1377762
TI  - [Efficacy of the use of a stabilized alpha2-macroglobulin concentrate in
      experimental burns].
AB  - The effectiveness of the use of a stabilized composition of alpha 2-macroglobulin
      concentrate obtained from fraction III of plasma proteins according to Cohn in
      burn disease in the experiment on guinea pigs was studied. Under the influence of
      intraabdominal administration for 4 days of alpha 2-macroglobulin concentrate
      with a stabilizer, healing of the burn wounds, normalization of a state of the
      animals occurred 2 times more rapidly than in control ones, activity of acid
      proteinases restored by day 5 (in control--by day 14) due to increase in activity
      of proteolytic enzyme inhibitors.

PMID- 1377761
TI  - [A case of primary anterior mediastinal embryonal carcinoma: report of a case].
AB  - A 15-year-old man was admitted to our hospital because of chest pain. The chest x
      ray film and CT scan revealed a large anterior superior mediastinal mass. The
      serum alpha-fetoprotein (AFP) value was raised. Percutaneous biopsy of the tumor
      suggested embryonal carcinoma. The tumor was totally removed. Postoperatively
      combination chemotherapy including CDDP was performed. However the patient died
      of tumor recurrence 8 months after operation. AFP is very useful for its
      diagnosis and the follow-up of the clinical course.

PMID- 1377763
TI  - Basement membrane components enhance isolated enterocyte growth.
AB  - Isolated enterocyte transplantation may have a potential role in increasing
      intestinal surface area. However, enterocytes are notoriously difficult to grow.
      Basement membrane components (BMC) promote adherence, migration, and
      differentiation of enterocytes. Our aim was to determine if BMC enhance
      enterocyte growth. Twenty-nine rabbits had 5-cm ileal segments resected and
      serosal pouches (n = 22) created from the serosal surface of the colon.
      Harvesting of enterocytes by warm trypsinization resulted in 92 +/- 6% cell
      viability and yielded 5.0 +/- 2.4 10(6) enterocytes/cm intestine. Enterocytes
      (10(5) were cultured in vitro (n = 7) in 10 ml growth media in plain flasks and
      flasks coated with laminin alone or Matrigel (an extract of mouse basement
      membrane containing laminin plus Type IV collagen and heparan sulfate). The cells
      were subcultured at 2 weeks and examined after Geimsa staining at 4 weeks.
      Epithelial growth was confirmed by light microscopy and staining for cytokeratin
      and quantitated by image analysis (JAVA). Epithelial coverage of the flasks was
      greater with Matrigel (80 +/- 15%) than laminin (66 +/- 15%) which was greater
      than control (44 +/- 20%) (P less than 0.01). For in vivo studies 10(5) harvested
      cells were infused into the serosal pouches either in growth media (n = 9) or
      media + Matrigel (n = 13). Epithelial growth in the pouch was evaluated by
      qualitative scoring of cytokeratin staining. Cytokeratin staining was similar on
      control colon serosa (n = 5) and serosa after infusion of cells in media alone.
      However, Matrigel significantly enhanced the area, depth, and intensity of
      staining.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377764
TI  - Determination of the resection line in early esophageal cancer using
      intraoperative endoscopic examination with Lugol staining.
AB  - Determination of the resection line using intraoperative endoscopic examination
      with Lugol staining was performed when preoperative examinations such as an
      esophagogram could not be effectively carried out and the carcinoma was not
      palpable from the outer surface of the esophageal wall. During the past two
      years, we performed this technique on eight patients. The carcinoma was
      restricted within the epithelium in one, the mucosal layer in five, and the
      submucosal layer in two. Although intraepithelial carcinoma contiguous to the
      main lesion was seen in six and cancer multiplicity was evident in two, all of
      the resected stumps were free of any cancer tissue. There have been no cases of
      recurrence and a limited operation, such as distal esophagectomy, was able to be
      performed in six. Therefore, intraoperative endoscopic examination is useful for
      early esophageal cancer.

PMID- 1377765
TI  - Enucleation of a secondary esophageal mural tumor.
AB  - Metastatic tumors to the esophagus have been described as having the imaging
      characteristics of benign mural tumors such as leiomyomata, but application of
      enucleation in treating such tumors has not been described. Our report describes
      long esophageal myotomy and enucleation of tumor for palliation of dysphagia due
      to a mural tumor originating from a lung primary.

PMID- 1377766
TI  - Cholinergic influence of K(+)-evoked release of endogenous histamine from rat
      hypothalamic slices in vitro.
AB  - The effects of cholinergic agents on the K(+)-evoked release of endogenous
      histamine from hypothalamic slices of rats were examined by a superfusion method
      in vitro. Acetylcholine and carbamylcholine significantly inhibited K(+)-evoked
      release of histamine from the slices, and the effect of acetylcholine was
      antagonized by the muscarinic antagonist atropine. On the other hand, nicotine
      significantly enhanced the K(+)-evoked release and its effect was antagonized by
      the nicotinic antagonist hexamethonium. The effects of carbamylcholine and
      nicotine on histamine release from slices of whole hypothalamus and from slices
      of the anterior hypothalamic region, which do not contain cell bodies of the
      histaminergic neurons, were the same. Thus, the K(+)-evoked release of endogenous
      histamine from histaminergic fibers in the hypothalamic slices was inhibited by
      muscarinic agents and enhanced by nicotinic agents. These results suggest that
      muscarinic and nicotinic receptors exert antagonistic effects on the release of
      hypothalamic histamine from in vitro slice preparations. The cholinergic
      receptors modulating histamine release might be located presynaptically on the
      histaminergic terminals.

PMID- 1377767
TI  - Immune response of peripheral blood mononuclear cells to antigenic determinants
      within hepatitis B core antigen in HB virus-infected man.
AB  - Residues 72-146 within hepatitis B core Ag (HBcAg) represent T-cell recognition
      site in HB-virus-infected man. This study was undertaken to define critical
      residues involved in the immunogenicity of dominant T-cell determinants of HBcAg.
      For this purpose, p120-131 and its analog (p120-131 [A] containing alanine
      substitutions at residues 122 and 125, which were identified as epitopic residues
      in mice, were synthesized. These peptides and recombinant HBcAg were analyzed for
      their ability to stimulate peripheral blood mononuclear cells (PBMC) from 25
      patients with chronic HBV infection and three patients with acute hepatitis B.
      PBMC from 18 out of 28 patients showed significantly increased IFN-gamma
      production and proliferative response in the presence of recombinant HBcAg. Eight
      patients responded to the two peptides, while 12 patients did not. Four patients
      responded only to p120-131, and four displayed a response only to p120-131 [A].
      The responses to the two peptides were similar among HBeAg-positive and anti-HBe
      positive patients, and did not depend on disease activity, except for HBeAg
      positive asymptomatic carriers in whom there was no response to any additive.
      These results indicate that immune responses to p120-131 and its analog were
      similar in our patient groups. The dominant epitopic residues in this region of
      HBcAg may differ between man and mouse.

PMID- 1377768
TI  - Increased steady-state levels of alpha-fetoprotein mRNA in hepatocellular
      carcinoma: an analysis by in situ hybridization.
AB  - The molecular basis for the augmented production of alpha-fetoprotein is unknown.
      We have used in situ hybridization of alpha-fetoprotein cDNA to malignant
      hepatocytes to establish if increased serum alpha-fetoprotein concentrations are
      related to detectable steady-state levels of alpha-fetoprotein mRNA in
      hepatocytes. Tumor tissue from four patients with histologically confirmed
      hepatocellular carcinoma were examined, and the results compared to fetal liver.
      Northern blot hybridization for alpha-fetoprotein mRNA in tumor tissue was also
      analyzed. As expected a high number of grains was observed in fetal liver tissue,
      indicative of high levels of alpha-fetoprotein mRNA physiologically present
      during pre-natal development. Sections from all patients with high serum
      concentrations of alpha fetoprotein showed appreciable hybrid formation, which
      correlated semi-quantitatively with the serum concentrations. However, hybrids
      were not detected in a patient with a normal serum alpha-fetoprotein. The high
      alpha-fetoprotein mRNA levels in fetal and neoplastic liver suggest that gene
      transcription is the mechanism of alpha-fetoprotein production in malignancy,
      although the control of this mechanism remains speculative.

PMID- 1377769
TI  - Luteinizing hormone response to an intravenous infusion of substance P in normal
      men.
AB  - The effect of synthetic substance P (SP), infused intravenously in doses of 0.5,
      1.0, or 1.5 pmol/kg-1/min-1 for 60 minutes, on gonadotropin secretion was
      evaluated in seven healthy men. SP tests and a control test with normal saline
      were randomly performed at weekly intervals. During the tests, SP infusion did
      not produce untoward side effects or changes in blood pressure. Plasma
      testosterone concentrations were normal in all subjects and remained unmodified
      during all tests, regardless of the infused dose of SP. Plasma luteinizing
      hormone (LH) levels were not modified when either normal saline or the lowest
      dose of SP were infused, whereas they were significantly increased in a dose
      dependent fashion when larger amounts of SP were administered. In contrast,
      plasma follicle-stimulating hormone (FSH) concentrations did not change
      significantly during any test. These data demonstrate for the first time in
      normal men that the systemic infusion of SP stimulates LH release, without
      modifications of FSH secretion.

PMID- 1377770
TI  - Combination chemotherapy with cisplatin, vindesine and mitomycin-C for advanced,
      inoperable non-small-cell lung cancer.
AB  - OBJECTIVES: To assess the activity of chemotherapy with cisplatin, vindesine and
      mitomycin-C (PVM) in advanced non-small-cell lung cancer (NSCLC) and to test the
      feasibility of preemptive therapy with PVM. DESIGN AND SETTING: A phase II
      clinical trial of PVM in patients with NSCLC treated at the Royal Prince Alfred
      Hospital between June 1987 and July 1990. PATIENTS: Forty-one patients with
      advanced, inoperable or recurrent NSCLC--22 women, 19 men, with a median age of
      51 years. Thirteen patients had been treated previously with radiotherapy and/or
      surgery; 18 had extrathoracic metastases. Four patients previously deemed
      inoperable were treated preemptively with PVM before proceeding to radical
      surgery. INTERVENTIONS: Cisplatin 100 mg/m2, vindesine 5 mg and mitomycin-C 8
      mg/m2, all given intravenously on Day 1, with vigorous hydration and antiemetic
      therapy. Cycles were repeated every four weeks. MAIN OUTCOME MEASURES: Objective
      tumour response to treatment, patient survival time, time to treatment failure,
      and treatment toxicity. RESULTS: There was one complete tumour response to PVM
      and 15 partial responses; 14 patients had stable disease and nine had progressive
      disease--yielding an objective response rate (complete plus partial responses) of
      39% (16/41; 95% confidence interval [CI], 24%-56%). Responses were documented in
      all histological subgroups, in both locally advanced and disseminated disease,
      and in recurrent disease. Median survival of the group was six months (95% CI, 5
      10 months; range, 0.5-19+ months), and is unchanged by exclusion of the four
      patients treated before surgery. Seven of the 41 patients (17%) survived 12
      months or longer. Median time to treatment failure in patients who had an
      objective response was six months (95% CI, 5-10 months). Grade 3 or 4 nausea and
      vomiting occurred in 21 patients (51%). Haematological, renal and neurological
      toxicity were not major problems; there were no deaths from treatment toxicity.
      CONCLUSION: PVM is an active regimen in advanced NSCLC and can produce durable
      remissions. The potential palliative effects of PVM in incurable disease must be
      weighed against the risk of subjective toxicity.

PMID- 1377771
TI  - Granulocyte colony stimulating factor in the management of chronic neutropenia.
AB  - OBJECTIVE: To report two cases of chronic neutropenic states successfully treated
      with granulocyte colony stimulating factor (G-CSF). CLINICAL FEATURES: A 23-year
      old man with severe congenital cyclic neutropenia causing lifelong recurrent
      infections and consequent debilitation presented with intractable infected leg
      ulcers. A 56-year-old man with acquired idiopathic neutropenia presented with
      severe perianal infection and sepsis. INTERVENTION AND OUTCOME: Both patients
      were successfully treated with recombinant G-CSF. CONCLUSION: G-CSF is an agent
      with major clinical potential for the therapy of primary neutropenic states.

PMID- 1377772
TI  - [Therapy of juvenile rheumatoid arthritis].
AB  - The correct drug treatment of JRA must consider the course and the subtype of the
      disease. Nonsteroidal antiinflammatory drugs are the first choice treatment,
      especially the recent ones which are more active and less toxic. The slow-acting
      antirheumatic drugs are the second choice treatment and must be employed in the
      chronically active stages of the disease; good results have been obtained with
      sulphasalazine and methotrexate both on clinical features and on blood
      biochemistry with relatively scarce side effects. Thymic hormones, cyclosporin A
      and intravenous immunoglobulins, though not yet widely experienced, can represent
      a worthwhile alternative to standard treatment in carefully selected cases.
      Steroids must be used only in special cases (particularly aggressive systemic
      JRA, carditis, severe anemia and those patients who fail to respond to usual
      treatments) and must be withdrawn as soon as possible to avoid adverse effects
      and steroid-addiction. Intraarticular long-acting steroids are the first choice
      treatment for rheumatoid monoarthritis.

PMID- 1377773
TI  - CfT-I: an LTR-retrotransposon in Cladosporium fulvum, a fungal pathogen of
      tomato.
AB  - A retrotransposon from the fungal tomato pathogen Cladosporium fulvum (syn.
      Fulvia fulva) has been isolated and characterised. It is 6968 bp in length and
      bounded by identical long terminal repeats of 427 bp; 5 bp target-site
      duplications were found. Putative first- and second-strand primer binding sites
      were identified. Three long open reading frames (ORFs) are predicted from the
      sequence. The first has homology to retroviral gag genes. The second includes
      sequences homologous to protease, reverse transcriptase, RNAse H and integrase,
      in that order. Sequence comparisons of the predicted ORFs indicate that this
      element is closely related to the gypsy class of LTR retrotransposons. Races of
      the pathogen exhibit polymorphisms in their complement of at least 25 copies of
      the sequence. Virus-like particles which co-sediment with reverse transcriptase
      activity were observed in homogenates of the fungus. This is the first report of
      an LTR retrotransposon in a filamentous fungus.

PMID- 1377774
TI  - PMI40, an intron-containing gene required for early steps in yeast mannosylation.
AB  - We have previously described a temperature-sensitive pmi40-1 mutant of
      Saccharomyces cerevisiae which is defective in glycosylation and secretion
      because of a thermolabile phosphomannose isomerase (PMI) activity. Inactivation
      of PMI at the restrictive temperature of 37 degrees C prevents synthesis of the
      GDP-mannose and dolichol-phosphate-mannose required for a number of critical
      mannosyl transfer reactions and results in cell death. Here, we report the
      isolation of the PMI40 gene by complementation of the corresponding mutation. The
      PMI40 gene contains an efficiently spliced intron which differs from the majority
      of those so far identified in S. cerevisiae in that it is short and the branch
      forming structure has an AACTAAC motif replacing the highly conserved consensus
      TACTAAC. The 48.2-kDa protein predicted to be encoded by PMI40 contains amino
      acid sequences corresponding to those of internal peptides derived from purified
      S. cerevisiae PMI. Deletion of the PMI40 coding sequence results in a strain
      requiring D-mannose for growth. The PMI40 gene is located on chromosome V, and
      its transcription is increased 12-fold when cells are grown on D-mannose as sole
      carbon source instead of D-glucose. PMI enzyme activity, however, is not
      increased in D-mannose-grown cells, and PMI protein levels remain constant,
      suggesting that the PMI40 gene is subject to additional levels of regulation.

PMID- 1377776
TI  - Analysis of clastogenic effect of Porto Alegre drinking water supplies on mouse
      bone marrow cells.
AB  - Studies were conducted to evaluate the clastogenic activity of drinking water
      from Porto Alegre and Guaiba (Rio Grande do Sul, Brazil) estuarine waters. Mouse
      bone marrow was the target organ. C57B1/6 male and female mice received the water
      samples as their only liquid supply. Bone marrow cells were collected on the 16th
      day after the beginning of treatment. The analysis of metaphases demonstrated
      that the water supplies did not increase the structural chromosome aberration
      frequencies compared to the control groups. Concerning numerical alterations,
      only one treated female group showed a significant difference (loss of one
      chromosome) when compared to the control group, but this result is not considered
      relevant.

PMID- 1377777
TI  - Passive smoking and sister-chromatid exchanges in lymphocytes.
AB  - The object of this study was to determine whether exposure to environmental
      tobacco smoke is associated with DNA damage reflected by the frequency of sister
      chromatid exchange (SCE) in lymphocytes. Within a cross-sectional design, 106
      male non-smoking adults, employees of two administrative companies, were divided
      on the basis of self-reported exposure into high and low passive smoking groups.
      The high exposed subjects (passive smokers, n = 50) lived with smokers, worked
      with smokers and were exposed to tobacco smoke for an average of 70 h/week. The
      low exposed non-smokers (n = 56) were exposed for an average of 5 h/week. Plasma
      cotinine levels for the passive smokers ranged between 0.4 and 9.0 ng/ml (median
      1.4 ng/ml), and for the low exposed group between 0.0 and 1.9 ng/ml (median 0.4
      ng/ml) (p less than 0.0001; Mann-Whitney test). No difference was observed
      between the two groups in the frequency of SCEs in lymphocytes: 4.66 +/- 0.05 for
      passive smokers and 4.68 +/- 0.04 for low exposed non-smokers (mean +/- SEM) (p =
      0.80; t-test). Reclassification of subjects on the basis of plasma cotinine
      levels did not change the results substantially. These results are in accordance
      with observations that the increase in cancer risk due to passive smoking is
      small in comparison with the increase due to active smoking. The SCE test may be
      too insensitive to be useful for the evaluation of possible cytogenetic effects
      related to passive smoking.

PMID- 1377778
TI  - Effects of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) on somatic mutation in a
      soybean test system.
AB  - The mutagenic activity of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was
      assayed in heterozygous soybean plants (Y11y11), based on the appearance of
      mutational spots (yellow, dark green and twin) on the leaves. When soybean seeds
      were treated with IQ at concentrations of 0.01-0.1 microgram/ml, the frequency of
      mutational spots per leaf increased significantly in proportion to the
      concentration of IQ. At higher concentrations IQ was toxic. The mutagenicity of
      IQ was enhanced by pretreatment with the hepatic S9 fraction from Aroclor-induced
      rats. The numbers of yellow and dark green spots per leaf increased markedly by
      the treatment with IQ and S9-activated IQ, but the number of twin spots did not
      increase.

PMID- 1377775
TI  - Requirement of mosXe protein kinase for meiotic maturation of Xenopus oocytes
      induced by a cdc2 mutant lacking regulatory phosphorylation sites.
AB  - The p34cdc2 protein kinase is a component of maturation-promoting factor, the
      master regulator of the cell cycle in all eukaryotes. The activity of p34cdc2 is
      itself tightly regulated by phosphorylation and dephosphorylation. Predicted
      regulatory phosphorylation sites of Xenopus p34cdc2 were mutated in vitro, and in
      vitro-transcribed RNAs were injected into Xenopus oocytes. The cdc2 single
      mutants Thr-14----Ala and Tyr-15----Phe did not induce germinal vesicle breakdown
      (BVBD) upon microinjection into oocytes. In contrast, the cdc2 double mutant Ala
      14/Phe-15 did induce GVBD. Both the Ala-14 and Ala-14/Phe-15p34cdc2 mutants were
      shown to coimmunoprecipitate cyclin B1 and to phosphorylate histone H1 in immune
      complex kinase assays. Microinjection of antisense oligonucleotides to c-mosXe
      was used to demonstrate the role of mos protein synthesis in the induction of
      GVBD by the Ala-14/Phe-15 cdc2 mutant. Thr-161 was also mutated. p34cdc2 single
      mutants Ala-161 and Glu-161 and triple mutants Ala-14/Phe-15/Ala-161 and Ala
      14/Phe-15/Glu-161 failed to induce GVBD in oocytes and showed a decreased binding
      to cyclin B1 in coimmunoprecipitations. Each of the cdc2 mutants was also assayed
      by coinjection with cyclin B1 or c-mosXe RNA into oocytes. Several of the cdc2
      mutants were found to affect the kinetics of cyclin B1 and/or mos-induced GVBD
      upon coinjection, although none affected the rate of progesterone-induced
      maturation. We demonstrate here the significance of Thr-14, Tyr-15, and Thr-161
      of p34cdc2 in Xenopus oocyte maturation. In addition, these results suggest a
      regulatory role for mosXe in induction of oocyte maturation by the cdc2 mutant
      Ala-14/Phe-15.

PMID- 1377779
TI  - Genotoxic action of an aqueous extract of Heliotropium curassavicum var.
      argentinum.
AB  - Heliotropium curassavicum var. argentinum is widely employed in gout, rheumatism,
      neuralgias, arteriosclerotic disorders, muscular algias, phlebitis, varix and
      other illnesses. In order to analyze the genotoxic effect produced in vitro by
      this medicinal plant, chromosomal aberrations (CA), mitotic index (MI) and
      anaphase delay (AD) were studied in the CHO cell line, with and without the
      addition of S9 mix. Prepared according to the Argentine pharmacopeia 0.1, 1, 10
      and 100 micrograms/ml plant decoction (aqueous extract) were assayed. One hundred
      cells per culture were studied for CA and AD, while MI was calculated for 2000
      nuclei. The results revealed a significant increase in the percentage of abnormal
      metaphases (p less than 0.001) and in total aberrations (p less than 0.001). Both
      the MI and the AD affected the cell cycle. All results were enhanced by the
      addition of an S9 fraction. The toxic effect could be associated with
      pyrrolizidine alkaloids and their N-oxides, which through a process of in vitro
      metabolism become activated by microsomal oxidation and change into pyrrolic
      derivatives.

PMID- 1377780
TI  - Mutagenic potential of toluidine blue evaluated in the Ames test.
AB  - Toluidine blue is a vital, metachromatic thiazine dye which is used as an adjunct
      in clinical examination for the early detection of asymptomatic recurrent or
      secondary primary carcinoma in individuals who are at high risk for developing
      oral cancer. Because available data on the mutagenicity of toluidine blue was
      limited and contradictory, this study was conducted to evaluate the mutagenic
      potential of toluidine blue in the in vitro Ames Salmonella test. Tester strains
      TA97a, TA98, TA100 and TA102 were used. Toluidine blue was tested at
      concentrations of 0.1, 1.0, 10, 50, 100, 250 and 500 micrograms/plate, with and
      without S9 microsomal activation, and positive and negative controls were
      included. Results from tests without S9 showed a significant increase (p less
      than 0.05) in number of revertants in TA102 and in TA97a with 50 and 100
      micrograms toluidine blue/plate, respectively. In tests with S9 activation, doses
      of toluidine blue ranging from 10 to 250 micrograms/plate induced dose-related
      increases in the number of revertants in all 4 strains. The results of this study
      indicate that toluidine blue has a mutagenic effect in the Ames test.

PMID- 1377781
TI  - Comparison of the Gene-Tox and RTECS data bases as predictors of carcinogenic
      potency.

PMID- 1377782
TI  - Sister-chromatid exchange induction produced by in vivo and in vitro exposure to
      alpha-asarone.
AB  - The effect of alpha-asarone, a chemical with hypocholesterolemic properties
      extracted from Guatteria gaumeri, on SCE induction was studied both in human
      lymphocytes in vitro and in murine bone marrow cells in vivo. A slight but
      consistent increase in SCE was observed in both biological systems.

PMID- 1377783
TI  - Mutagenicity of N,N'-dimethylurea and methylamine hydrochloride in the Ames
      Salmonella/microsome test: absence of mutagenic response.
AB  - Methyl isocyanate (MIC) in aqueous solution forms methylamine (MA) and N,N'
      dimethylurea (DMU). MA in buffered system further converts into its salt form,
      methylamine hydrochloride (MAH). Therefore, MAH and DMU were evaluated for their
      mutagenic activity in the in vitro Ames Salmonella/microsome mutagenicity test.
      The liquid preincubation protocol was followed, using tester strains TA98, TA100
      and TA104 of Salmonella typhimurium, in the presence of 0, 5, 15 and 30% Aroclor
      1254-induced rat liver S9 mixture. DMU and MAH did not induce a mutagenic
      response in any of the tester strains, both in the presence and in the absence of
      S9 mixture. The results therefore confirm that MIC in its native form or as its
      unknown metabolites is responsible for the mutagenic activity reported earlier by
      us in the his tester strains TA100 and TA104 of Salmonella typhimurium (Mutation
      Res., 204 (1988) 123-129) and not due to its hydrolysis products, MA or DMU.

PMID- 1377784
TI  - Suppressing effect of vanillin on chromosome aberrations that occur spontaneously
      or are induced by mitomycin C in the germ cell line of Drosophila melanogaster.
AB  - In order to investigate the anticlastogenic effect of vanillin on ring-X loss, D.
      melanogaster females exposed to different vanillin concentrations were crossed
      with non-treated, MMC- or MMS-treated males. The results obtained with this in
      vivo investigation showed a significant inhibition of vanillin in the frequencies
      of spontaneous ring-X loss--59, 56, 38 and 36%--at the different concentrations
      used. In addition, vanillin treatment caused a significant suppression of MMC
      induced ring-X loss. This decrease was observed only in the first 3 days after
      the interruption of vanillin treatment and at the concentrations of 0.5 and 1% of
      this flavoring agent. In contrast, vanillin did not show any effect on chromosome
      loss provoked by MMS. Therefore, the ring-X loss-decreasing effect of vanillin
      seemed to depend on the quality of DNA lesions and consequently on a specific
      enzymatic repair process present in the oocytes of D. melanogaster.

PMID- 1377785
TI  - Modulation of the mutagenicity of three dinitropyrene isomers in vitro by rat
      liver S9, cytosolic, and microsomal fractions following chronic ethanol
      ingestion.
AB  - The effects of chronic ethanol feeding of rats on the ability of liver fractions
      to modulate the bacterial mutagenicity of three dinitropyrene isomers (1,3-, 1,6-
      and 1,8-DNP), which require bacterial enzymes but not an exogenous enzyme source
      for activation, were studied. The mutagenicity of the DNP isomers toward S.
      typhimurium TA98 and TA100 was attenuated in the presence of post-mitochondrial
      supernatants (S9) from both ethanol-fed and pair-fed rats albeit, that from the
      ethanol-fed group was more efficient in lowering the mutagenicity. The cytosolic
      fraction from ethanol-fed rats enhanced the mutagenicity of all of the DNP
      isomers in TA100. The most notable enhancement was with 1,3-DNP in which a more
      than 4-fold enhancement was obtained. Cytosol from pair-fed rats enhanced only
      the mutagenicity of 1,3-DNP, this by 2.9-fold. Cytosolic NADPH-nitroreductase
      activity from ethanol-treated rats toward 1,6-, 1,8- and 1,3-DNP was increased
      2.8-, 1.7- and 1.3-fold, respectively over pair-fed controls. Cytosolic NADH
      nitroreductase from ethanol-fed rats was increased with 1,3-DNP (1.7-fold) and
      1,8-DNP (1.4-fold) as substrates, but not with 1,6-DNP. Microsomes decreased the
      mutagenicity of DNP similarly to S9, i.e., fractions from ethanol-fed rats were
      more efficient than those of pair-fed rats in deactivating all the DNP isomers.
      Per mg of protein, detoxification of DNP by S9 was more efficient than with
      microsomes, thus both cytosolic and microsomal enzymes are required for maximal
      detoxification. In summary, ethanol feeding modulates both the augmented
      cytosolic activation of DNP to mutagens and the deactivation of the direct-acting
      mutagenicity of DNP by microsomes. In combination, as is the case with S9, the
      microsomal detoxifying activity outcompetes the cytosolic activation.

PMID- 1377786
TI  - A Babesia bovis 225-kilodalton protein located on the cytoplasmic side of the
      erythrocyte membrane has sequence similarity with a region of glycogen
      phosphorylase.
AB  - A Babesia bovis gene sequence is described which encodes a geographically
      conserved epitope (recognized by monoclonal antibody (mAb) 23.8.34) of a 225-kDa
      protein located on the surface of merozoites and associated with the infected
      erythrocyte membrane. The gene sequence, derived from both genomic and cDNA
      copies, is 2044 bp long and has one long open reading frame encoding about one
      third of the 225-kDa protein. The open reading frame is expressed in an
      approximately 6,400 nucleotide RNA transcript. A 73-amino acid sequence occurs as
      4 complete and 1 partial tandem repeats at the carboxy terminus of the partial
      protein sequence. The epitope recognized by mAb 23.8.34 was localized to the
      repeat region. Based on epitope localization with mAb 23.8.34, the repeat was
      exposed on the surface of merozoites and located near the cytoplasmic face of the
      erythrocyte membrane. The amino terminus of the protein was non-repetitive and
      had 21% identity (60% similarity) to glycogen phosphorylase over a region of 151
      amino acids. In addition, the corresponding 5' DNA sequence hybridized to as many
      as 8 restriction fragments on Southern blots of genomic DNA. In contrast, the DNA
      sequence of the repeat hybridized to a single fragment. Both the repeat and
      multiple non-repeat DNA sequences were detected in a different geographic strain
      of B. bovis. These results indicate that the 5' end of the 225-kDa protein gene
      is related to a larger gene family, independent of the 3' end of the gene
      encoding the repeat.

PMID- 1377787
TI  - Identification of the uncultured bacillus of Whipple's disease.
AB  - BACKGROUND: Whipple's disease is a systemic disorder known for 85 years to be
      associated with an uncultured, and therefore unidentified, bacillus. METHODS: We
      used a molecular genetic approach to identify this organism. The bacterial 16S
      ribosomal RNA (rRNA) sequence was amplified directly from tissues of five
      unrelated patients with Whipple's disease by means of the polymerase chain
      reaction, first with broad-range primers and then with specific primers. We
      determined and analyzed the nucleotide sequence of the amplification products.
      RESULTS: A unique 1321-base bacterial 16S rRNA sequence was amplified from
      duodenal tissue of one patient. This sequence indicated the presence of a
      previously uncharacterized organism. We then detected this sequence in tissues
      from all 5 patients with Whipple's disease, but in none of those from 10 patients
      without the disorder. According to phylogenetic analysis, this bacterium is a
      gram-positive actinomycete that is not closely related to any known genus.
      CONCLUSIONS: We have identified the uncultured bacillus associated with Whipple's
      disease. The phylogenetic relations of this bacterium, its distinct morphologic
      characteristics, and the unusual features of the disease are sufficient grounds
      for naming this bacillus Tropheryma whippelii gen. nov. sp. nov. Our findings
      also provide a basis for a specific diagnostic test for this organism.

PMID- 1377788
TI  - A bovine albumin peptide as a possible trigger of insulin-dependent diabetes
      mellitus.
AB  - BACKGROUND: Cow's milk has been implicated as a possible trigger of the
      autoimmune response that destroys pancreatic beta cells in genetically
      susceptible hosts, thus causing diabetes mellitus. Studies in animals have
      suggested that bovine serum albumin (BSA) is the milk protein responsible, and an
      albumin peptide containing 17 amino acids (ABBOS) may be the reactive epitope.
      Antibodies to this peptide react with p69, a beta-cell surface protein that may
      represent the target antigen for milk-induced beta-cell--specific immunity.
      METHODS: We used immunoassays and Western blot analysis to analyze anti-BSA
      antibodies in the serum of 142 children with insulin-dependent diabetes mellitus,
      79 healthy children, and 300 adult blood donors. Anti-ABBOS antibodies were
      measured in 44 diabetic patients at the time of diagnosis, three to four months
      later, and one to two years later. RESULTS: All the diabetic patients had
      elevated serum concentrations of IgG anti-BSA antibodies (but not of antibodies
      to other milk proteins), the bulk of which were specific for ABBOS: The mean (+/-
      SE) concentration was 8.5 +/- 0.2 kilofluorescence units (kfU) per microliter, as
      compared with 1.3 +/- 0.1 kfU per microliter in the healthy children. IgA
      antibodies were elevated as well, but not IgM antibodies. The antibody
      concentrations declined after diagnosis, reaching normal levels in most patients
      within one to two years. The initial decline involved anti-ABBOS--specific
      antibodies almost exclusively. Much lower serum concentrations of anti-BSA
      antibodies were found in all 379 control subjects, but only 2.5 percent of them
      had small amounts of ABBOS-specific IgG. CONCLUSIONS: Patients with insulin
      dependent diabetes mellitus have immunity to cow's-milk albumin, with antibodies
      to an albumin peptide that are capable of reacting with a beta-cell--specific
      surface protein. Such antibodies could participate in the development of islet
      dysfunction.

PMID- 1377789
TI  - Whipple's disease--rare malady with uncommon potential.

PMID- 1377792
TI  - Isolation and characterization of two novel peptide amides originating from
      myelin basic protein in bovine brain.
AB  - During a systematic search for peptides that possess the C-terminal amide
      structure, two novel peptide amides, one with a tyrosine amide and the other with
      an alanine amide were isolated from bovine brain by acid extraction and
      sequential steps of reversed phase HPLC. Microsequence, amino acid and mass
      spectral analyses revealed the structures: Ac-Ala-Ala-Gln-Lys-Arg-Pro-Ser-Gln-Arg
      Ser-Lys-Tyr-amide and Ac-Ala-Ala-Gln-Lys-Arg-Pro-Ser-Gln-Arg-Ser-Lys-Tyr-Leu-Ala
      Ser-Ala-amide . These 12 and 16 residues peptides had the primary structure
      identical to the N-terminal fragment of myelin basic protein (MBP). The peptides
      were therefore designated myelin peptide amide-12 (MPA-12) and -16 (MPA-16).
      Unlike other amidated peptides, MPA might be generated from MBP by hydroxyl
      radicals produced via a Fenton reaction in situ. However, this unique amidation
      seems to occur exclusively to MBP in a site specific manner in the brain.

PMID- 1377791
TI  - Neurochemical and histological analysis of motor dysfunction observed in rats
      with methylnitrosourea-induced experimental cerebellar hypoplasia.
AB  - Histological and neurochemical changes related to motor dysfunction observed in
      rats after neonatal treatment with nitrosoureas were examined. Neonatal rats
      received subcutaneous injections of methylnitrosourea (MNU: 0.125 mmol/kg, s.c.)
      or ethylnitrosourea (ENU: 0.25 mmol/kg, s.c.) daily at 4,5,6 and 7 days post
      partum, a period of cerebellar granule cell, stellate cell and basket cell
      formation. At 14 days and 45 days after birth, MNU-treated rats displayed a
      lowering in motor coordination skills measured by tests of retainment ability on
      a rod of 26 mm diameter, chinning-climbing ability on parallel rods or retainment
      ability on a rotating rod. Histological examination at 14 days after birth showed
      a cerebellar hypoplasia with reduced cellularity of the internal granule cell
      layer and a disperse disposition of Purkinje cells in the granule cell layer.
      Cerebellar growth and cerebellar content and concentration of DNA were remarkably
      reduced in the MNU-treated rat. The degree of the reduction in cerebellar content
      of glutamic acid paralleled the degree of the cerebellar hypoplasia at 14 and 45
      days after birth. In contrast, the concentrations of gamma-aminobutyric acid,
      acetylcholine, 5-hydroxytryptamine and norepinephrine were significantly
      increased by MNU treatment. ENU treatment control did not exert any significant
      changes in the neurotransmitters and motor coordination. These results suggest
      that the motor dysfunctions observed in MNU treated rats are induced by
      unbalanced output activities from Purkinje cells to motor neurons.

PMID- 1377793
TI  - Tumor-specific binding of radiolabeled G-22 monoclonal antibody in glioma
      patients.
AB  - Iodine-131-labeled G-22 monoclonal antibody F(ab')2 fragment reaching
      specifically with a glioma-associated surface glycoprotein was administered to 12
      glioma patients to investigate its use in radioimaging of intracranial gliomas.
      No immediate or delayed side effects were attributable to antibody injection.
      Nine patients received the radiolabeled complex intravenously. The images of low
      grade gliomas were generally poor and disappeared within 4 days. High-contrast
      images were obtained beyond the 7th day in high-grade gliomas except one case in
      the pineal region. Three patients received intraventricular or intratumoral
      administration. Clear images of all tumors were demonstrated from the 2nd until
      later than the 7th day. One patient with cerebrospinal fluid (CSF) dissemination
      of brainstem glioma demonstrated negative CSF cytology after intraventricular
      administration.

PMID- 1377790
TI  - Vasorelaxing effect in rat thoracic aorta caused by fraxinellone and dictamine
      isolated from the Chinese herb Dictamnus dasycarpus Turcz: comparison with
      cromakalim and Ca2+ channel blockers.
AB  - The components of Dictamnus dasycarpus Turcz were tested for their vasorelaxing
      effect on the rat aorta, and fraxinellone and dictamine were shown to be
      effective vasorelaxants. In high K+ (60 mmol/l) medium, Ca2+ (0.03 to 3 mmol/l)
      induced vasoconstriction was inhibited concentration-dependently by both agents.
      The IC50 for fraxinellone and dictamine were calculated to be about 25 mumol/l
      and 15 mumol/l (for Ca2+ concentration of 1 mmol/l), respectively. Cromakalim
      (0.2-10 mumol/l) relaxed aortic rings precontracted with 15 but not 60 mmol/l of
      K+. Fraxinellone and verapamil were more potent and effective in producing
      relaxation in 60 mmol/l than in 15 mmol/l K(+)-induced contraction. However,
      dictamine was more potent in producing relaxation in 15 mmol/l K(+)-induced
      contraction. Nifedipine (1 mumol/l), dictamine (100 mumol/l) and fraxinellone
      (100 mumol/l) relaxed the aortic contraction caused by KCl or Bay K 8644. The
      tonic contraction elicited by noradrenaline (NA, 3 mumol/l) was also relaxed by
      dictamine (500 mumol/l), but not by fraxinellone (500 mumol/l) in the nifedipine
      (1 mumol/l)-treated aorta. This relaxing effect of dictamine persisted in
      endothelium-denuded aorta. Glibenclamide (10 mumol/l) shifted the concentration
      relaxation curve of cromakalim, but not that of dictamine, to the right in rat
      aortic rings precontracted with NA. Dictamine (500 mumol/l) did not affect tonic
      contraction of NA which are reduced by H-7 (1 mumol/l) in Ca(2+)-depleted medium.
      In conclusion, fraxinellone is a selective blocker of voltage-dependent Ca2+
      channel, while dictamine relaxed the rat aorta by suppressing the Ca2+ influx
      through both voltage-dependent and receptor-operated Ca2+ channels.

PMID- 1377794
TI  - Brain tumors manifesting as intracranial hemorrhage.
AB  - The clinical course and computed tomographic (CT) findings of 23 patients with
      brain tumors manifesting as tumoral hemorrhage were reviewed. The most common
      symptoms were headache and clouding of consciousness. A CT finding of a lesion
      located next to a solid or irregular clot indicated intratumoral hemorrhage.
      Precontrast CT demonstrating an indent on the hematoma surface was a valuable
      indicator of tumoral hemorrhage. A CT finding of accumulated levels of
      blood/fluid or a hyperdense mass containing small hematoma indicated intratumoral
      hemorrhage, and obscure hyperdensity indicated intratumoral hemorrhagic
      infarction. Such findings were often difficult to distinguish from spontaneous
      intracerebral hemorrhage due to other factors. The incidence of rebleeding from
      residual tumors was high, carrying a very poor prognosis, so radical removal of
      brain tumors with hemorrhage is very important.

PMID- 1377795
TI  - Partial resection of the gyrus rectus in pterional approach to anterior
      communicating artery aneurysms.
AB  - The effect of partial resection of the gyrus rectus during the unilateral
      pterional approach on surgical outcome was evaluated in 194 consecutive patients
      with ruptured anterior communicating artery aneurysms. Resection was performed
      more frequently in cases with poor clinical grade, in the acute stage, with
      superiorly directed aneurysms, and with high-positioned aneurysms. The surgical
      results were graded into three stages, and the follow-up results into five stages
      using the Glasgow Outcome Scale. Outcomes for 52 patients receiving gyrus rectus
      resection were compared with those for 142 patients without resection. There were
      no apparent effects caused by gyrus rectus resection on outcome.

PMID- 1377796
TI  - PTA of supra-aortic arteries with temporary balloon occlusion to avoid distal
      embolism.
AB  - Percutaneous transluminal angioplasty (PTA) was carried out in eight patients
      with cervical arterial stenosis; six in the subclavian and brachiocephalic
      arteries (5 with subclavian steal syndrome), one in the common carotid artery,
      and one in both the brachiocephalic and common carotid arteries (with subclavian
      steal syndrome). The PTA balloon catheters were introduced via the femoral artery
      in seven and brachial artery in one. To prevent distal embolization through the
      vertebral and internal carotid arteries, the blood flow in these vessels was
      temporarily occluded with a balloon catheter. The dilation of the stenotic areas
      was generally satisfactory. Antegrade blood flow was promptly obtained in the
      vertebral artery even in patients with subclavian steal syndrome. In all
      patients, the clinical symptoms improved. Two patients underwent repeat PTA
      because of restenosis.

PMID- 1377797
TI  - Long-term follow-up of cerebral blood flow in patients with ruptured cerebral
      aneurysm.
AB  - The xenon-133 inhalation technique was used to make three measurements of
      regional cerebral blood flow (CBF) in 34 patients with ruptured cerebral
      aneurysm: in the acute period (less than 14 days) after subarachnoid hemorrhage,
      in the subacute period (15-30 days), and in the chronic period (12-24 months).
      The hemispheric mean value of initial slope index was used as the mean CBF. The
      clinical outcomes were classified into good recovery (GR) (24 cases), moderate
      disability (MD) (5), and severe disability (SD) (5) on the Glasgow Outcome Scale.
      In all periods, the mean CBF significantly correlated with the outcome. GR
      patients had the highest mean CBF, MD patients the intermediate mean CBF, and SD
      patients the lowest mean CBF. GR patients had a near-normal mean CBF by the
      chronic period, while SD patients showed no significant CBF recovery throughout
      the course.

PMID- 1377798
TI  - Absence of response to hypothalamic stimulation test in brain death.
AB  - Immunoreactive corticotropin-releasing hormone (CRH) and growth hormone-releasing
      hormone (GHRH) are present in the plasma of the brain dead patients. These
      hypothalamic hormones may reflect some residual brain function after brain death.
      To examine the hypothalamic function, insulin-induced hypoglycemia and arginine
      infusion were performed in brain dead patients. Plasma CRH and GHRH were present
      initially, but levels did not increase significantly for 120 minutes after
      insulin injection. GH, adrenocorticotropic hormone, and cortisol levels did not
      increase either. Arginine load did not induce GH. These results suggest that
      hypothalamic hormones in the plasma after whole brain death do not reflect
      hypothalamic functions. The hormones may originate from extrahypothalamic sources
      such as the pancreas or adrenal gland.

PMID- 1377799
TI  - Cerebral paragonimiasis--report of five cases.
AB  - Five cases of cerebral paragonimiasis presenting with hemianopsia, convulsion,
      and gait disturbance are discussed. The cases were all in the chronic stage. The
      intradermal paragonimiasis reaction, complement fixation, and Ouchterlony tests
      were not useful for diagnosis. Computed tomography demonstrated calcifications in
      all cases in sites consistent with the foci of symptoms. Surgical treatment in
      two cases failed to improve symptoms.

PMID- 1377801
TI  - Unusual cranial metastasis from hepatoma presenting as isolated unilateral
      hypoglossal nerve paresis--case report.
AB  - A 45-year-old male presented with a rare right hypoglossal nerve paresis due to
      an unusual cranial metastatic tumor from hepatoma. Despite multi-drug
      chemotherapy and arterial embolization, he died about 1 year later. Such
      metastasis should be considered as the cause of isolated unilateral hypoglossal
      nerve paresis.

PMID- 1377800
TI  - Intracranial germinoma and Down's syndrome--case report.
AB  - A germinoma in the basal ganglia developed in a 9-year-old boy with Down's
      syndrome, presenting as left hemiparesis. An initial computed tomographic (CT)
      scan demonstrated no notable abnormalities, but serial CT scans followed the
      entire course of tumor growth. Subtotal removal and irradiation achieved tumor
      remission. This is the first case reported of intracranial germinoma associated
      with Down's syndrome.

PMID- 1377802
TI  - Cystic pineocytoma--case report.
AB  - Pineocytoma and pineoblastoma, originating from pineal parenchyma, are rare and
      usually solid. An unusual case of totally cystic pineocytoma in a 37-year-old
      female is reported. The tumor showed neuronal differentiation and had a good
      outcome. Prominent calcification associated with pineocytoma and pineoblastoma is
      an useful finding to differentiate these from benign pineal cysts.

PMID- 1377803
TI  - Steady state analysis of hypothalamic GnRH mRNA levels in male Syrian hamsters:
      influences of photoperiod and androgen.
AB  - An in situ hybridization assay, utilizing a free floating technique was used to
      estimate the steady state levels of hypothalamic luteinizing hormone-releasing
      hormone (GnRH) mRNA levels in the brains of male golden hamsters maintained in
      different photoperiods. In situ histochemistry was performed using a 32P-labelled
      66-nucleotide long oligomer complementary to the sequence of the human GnRH mRNA
      coding region. The oligonucleotide hybridized specifically to mRNA encoding the
      GnRH precursor as suggested by the distribution of labelled neurons and as shown
      by an RNAse protection assay on septal and preoptic-hypothalamic mRNA from
      gonadally regressed hamsters. To test the hypothesis that short-day photoperiods
      reduce GnRH synthesis, intact male hamsters or castrated males bearing
      subcutaneously inserted testosterone implants were exposed to long-day (14 h
      light:10 h dark) or short-day (10 h light 14 h dark) photoperiods for 4 weeks.
      Exposure to short day lengths never caused a decrease in GnRH expressing neurons
      and actually was associated with an increase in the number of radiolabelled cells
      specifically in the diagonal band of Broca/medial septum in the gonadally intact
      group. The mean number of grains per labelled cell for the short day animals
      similarly was not reduced from that seen in long day animals. The results are
      consistent with previous studies on photoperiod and GnRH content in the same
      brain regions and support the notion that the suppression of the synthesis of
      GnRH does not accompany the low levels of LH secretion observed during the early
      stages of reproductive quiescence in this species.

PMID- 1377804
TI  - Epitope analysis of senile plaque components in the hippocampus of patients with
      Parkinson's disease.
AB  - We conducted an epitope analysis of senile plaque (SP) proteins on hippocampal
      SPs in patients with Parkinson's disease (PD), using a library of antibodies to
      proteins implicated in the genesis of hippocampal SPs in Alzheimer's disease
      (AD). The library included antibodies to the beta-amyloid protein (beta-AP),
      domains outside the beta-AP in beta-amyloid precursor proteins (beta-APPs),
      ubiquitin, diverse neuronal cytoskeletal proteins, and polypeptides located
      mainly in axon terminals. We obtained samples of hippocampus at autopsy from 14
      PD patients, 10 of whom were demented. As in the AD hippocampus, the SPs detected
      by conventional stains in five of the 10 demented subjects contained the beta-AP
      and flanking domains in beta-APPs as well as epitopes in tau, neurofilament
      proteins, and synaptophysin. Further, with the exception of the beta-AP, epitopes
      in the other proteins were confined to the coronas of SPs, while clathrin light
      chain, microtubule-associated protein 5, and neural cell adhesion molecules were
      almost undetectable or absent in the neuropil occupied by SPs. The same group of
      antibodies rarely labeled SPs in the other five demented PD subjects or in the
      four nondemented PD subjects, and conventional stains for amyloid and
      neurofibrillary pathology revealed rare SPs in these cases. Hence, when
      conventional stains reveal lesions diagnostic of AD in PD patients, the molecular
      features of the hippocampal SPs in these patients are the same as those in SPs of
      the AD hippocampus.

PMID- 1377805
TI  - Protective effect of serotonin on migraine attacks.

PMID- 1377806
TI  - [Comparison of crystalloids and hydroxyethyl starch during normovolemic
      hemodilution. A study of hemodynamics and saturation measurement].
AB  - Normovolemic hemodilution at two different hematocrit values was performed in ten
      patients undergoing major surgery to evaluate changes of DO2, VO2 and CI. A Hct
      of 38% (low hemodilution) was reached by plasma replacement with ringer lactate
      infusion. A further hemodilution, a Hct of 30% (high hemodilution), was obtained
      by hydroxyethyl starch plus ringer lactate (1:2 ratio) infusion. A significant
      VO2 increase (p less than 0.01) occurred when hydroxyethyl starch plus ringer
      lactate infusions were employed as compared to ringer lactate alone. No changes
      in DO2 and CI were observed, the increase in VO2 measured during colloid infusion
      could suggest a better tissue perfusion and metabolic activity.

PMID- 1377807
TI  - [Endoscopic laser therapy in the palliative treatment of cancer of the
      esophagus].
AB  - Frequently when dysphagia first becomes manifest, esophageal carcinoma is already
      unresectable. Endoscopic laser therapy is a recently introduced method which can
      be used for the palliative treatment of esophageal cancer. By using the method
      the tumour is destroyed and the esophagus is recanalized, there is low incidence
      of complications, and the patient can be fed naturally thus improving quality of
      life. The method has been perfected over the past years and now offers excellent
      results.

PMID- 1377808
TI  - T gamma/delta lymphocytes in renal transplant recipients.
AB  - T gamma/delta lymphocytes are able to perform allospecific cytotoxicity and
      natural killer cytotoxicity in vitro. However, very little is known about their
      function in vivo. To investigate the possible involvement of T gamma/delta
      lymphocytes in the immune response to renal allografts, fine-needle aspiration
      biopsies and peripheral blood of 15 renal transplant recipients were studied
      during the first 4 weeks after transplantation. In addition peripheral blood of
      patients before transplantation, half a year and one year after transplantation
      was studied. No increase in the percentage of T gamma/delta lymphocytes in the
      fine-needle aspiration biopsies, including those taken during acute rejection
      episodes, was found. A significant decrease in the percentage of T gamma/delta
      lymphocytes was observed in peripheral blood after transplantation. We conclude
      that T gamma/delta lymphocytes seem to play no major role in the immune response
      to renal allografts.

PMID- 1377809
TI  - Staining of semithin tissue sections embedded in HPMA, quetol 523 and MMA.
AB  - Various tissues fixed in a mixture of formaldehyde and glutaraldehyde, and
      embedded in an improved 2-hydroxypropyl methacrylate mixture were employed for
      studying the fine structures of cells and tissues by light microscopy. The
      embedding mixture contained Quetol 523 and methyl methacrylate as a plasticizer
      without a cross-linker. The catalyst was QCU-1. The mixture had a low viscosity,
      was easy to handle and penetrated readily and completely into the specimen,
      producing a homogeneous block from which it was easy to cut sections of 1-2
      microns in thickness. A wide variety of stains have been employed with such
      sections and those reported here are hematoxylin-eosin, Azan and PAS. There was
      excellent preservation of alkaline phosphatase activity. A method of poststaining
      immunoperoxidase labeling was also applied to the mouse pancreas and examples of
      staining with insulin are included.

PMID- 1377810
TI  - Cloning and structural analysis of the human c-kit gene.
AB  - The recent identification of the mouse White spotting and Steel loci as genes
      encoding the c-kit receptor and its ligand, respectively, has shed light on the
      importance of this ligand and receptor in embryogenesis, melanogenesis and
      hematopoiesis. In order to determine if the c-kit proto-oncogene is involved in
      human disease, we isolated seven overlapping lambda recombinants, using a fetal
      brain cDNA, and characterized the normal human gene (KIT). The longest mapped
      transcript is 5230 bp, is alternatively spliced and includes 21 exons that span
      more than 70 kb of DNA. From the exon-intron structure, we have localized an
      alternative splice site to the 3' end of exon 9. The overall c-kit gene structure
      closely resembles that found in the CSF-1R gene (c-fms). This similarity includes
      a large first intron, the same number of exons containing translated sequence and
      very similar exon-intron boundaries. Using pulsed-field gel electrophoresis, we
      have linked KIT to the platelet-derived growth factor receptor A gene, with both
      residing on a 700-kb BssHI fragment. These data will allow investigation into the
      control of KIT expression and the potential to identify mutations or altered
      expression of this gene in human disease.

PMID- 1377811
TI  - Expression of the c-erbB-3 protein in normal human adult and fetal tissues.
AB  - c-erbB-3 is a member of the type I family of growth factor receptors which
      includes the epidermal growth factor (EGF) receptor and c-erbB-2. Whereas for EGF
      receptor and c-erbB-2 the expression patterns in normal tissues are well
      documented, there is currently little information available about the sites of c
      erbB-3 expression. In order to examine the normal tissue distribution of c-erbB
      3, polyclonal antibodies were raised against eight synthetic peptides
      corresponding to distinct sites on the intracellular domain of c-erbB-3. Of
      these, three produced antibodies which reacted with a 160-kDa protein on
      immunoblots of human embryonal cells (293 cells) transfected with the cDNA
      encoding c-erbB-3, and two of the three antibodies immunoprecipitated a protein
      of similar size from the same cells. These antibodies were used for
      immunochemical staining of a wide variety of normal human adult and fetal tissues
      employing formalin-fixed, paraffin-embedded material. The c-erbB-3 protein was
      identified in cells of the gastrointestinal, reproductive, respiratory and
      urinary tracts as well as the skin, endocrine and nervous system in a
      distribution distinctly different from that observed for EGF receptor and c-erbB
      2. The level of expression of the mRNA for c-erbB-3 was also examined in extracts
      of a selection of fetal tissues. In general the sites of mRNA and protein
      expression were concordant.

PMID- 1377813
TI  - Structural organization of the murine c-kit proto-oncogene.
AB  - The murine Kit receptor gene on chromosome 5 has been found to be frequently
      involved in germline mutations and rearrangements, leading to a characteristic
      set of severe developmental defects, known as the W phenotype. Here we describe
      the structure of the murine c-kit gene, based on restriction analysis of genomic
      phage clones and sequence determination of exon-intron boundaries. The Kit-coding
      region is distributed over 21 exons, most of which have sizes that range between
      100 and 200 base pairs. The 3' non-translated sequence and the 3' end of the
      coding region form a single large exon, which encompasses 2.3 kb and is flanked
      by polyadenylation signals. The entire region spans a genomic distance of at
      least 70 kb. Though the exonic demarcations of c-kit show remarkable similarity
      to those of the human c-fms gene (which encodes the highly related colony
      stimulating factor 1 receptor), no correlation could be found between the sizes
      of introns that separate homologous exon pairs. The data suggest that
      evolutionary pressures were confined to the conservation of structures of coding
      exons, whereas flanking regions were subject to large changes, owing to
      insertions and deletions. Finally, the analysis of the Kit genomic structure
      reveals that the inherited mutations of the Kit gene that have been reported thus
      far occur at various dispersed positions within the gene. Hence, the entire gene
      appears to have as yet unknown features which cause it to be frequently subject
      to mutations in murine germline tissues.

PMID- 1377812
TI  - Clonal characteristics of acute lymphoblastic cells derived from BCR/ABL p190
      transgenic mice.
AB  - The clonal and immunophenotypic characteristics of blood leukemic cells from
      BCR/ABL p190 transgenic mice were investigated. All cell populations evaluated in
      vivo and in vitro had B-lymphocyte progenitor immunophenotypes. Immunoglobulin
      (JH) rearrangement patterns provided evidence for clonal diversification at
      different sites in vivo. Multiple clones were established in vitro from two of
      these mice (nos. 730 and 753). These cells expressed BCR/ABL p190 protein
      tyrosine kinase (PTK) and were highly malignant on transfer to secondary
      recipients. Cells independently cloned in vitro shared identical immunophenotypes
      and clonal IgH rearrangements, but these were distinct from those of the dominant
      clones in the mouse from which they were derived. Nevertheless, in vitro clones
      from mouse no. 753 had an abnormal karyotype (chromosome 14 trisomy) in common
      with the dominant clone in blood, providing evidence for a hierarchy or clonal
      selection in vivo and in vitro. Two sets of in vitro clones proliferated
      independently of exogenous growth factors and stroma and released autocrine
      interleukin 7 growth factor activity. These data provide evidence for rapid
      divergent clonal evolution and selection of B-cell progenitors initiated by
      BCR/ABL p190, followed by other, secondary genetic events mirroring similar
      changes in the equivalent, highly malignant human leukemia Philadelphia (Ph)
      positive/B-precursor acute lymphoblastic leukemia (ALL).

PMID- 1377814
TI  - Head trauma and its sequelae.

PMID- 1377815
TI  - Voltage-gated Ca entry in isolated bovine capillary endothelial cells: evidence
      of a new type of BAY K 8644-sensitive channel.
AB  - Isolated bovine capillary endothelial cells have been examined for voltage
      dependent Ca entry. All cells displayed a low threshold activity, with the main
      characteristics of a T-type transient current, when examined using whole-cell
      recording for activation and inactivation and cell-attached conditions or inside
      out patches for the elementary conductance (8 pS). 25% of the cells displayed an
      additional sustained current in 5 mM CaCl2 above -40 mV, which was enhanced by
      application of BAY K 8644, but almost insensitive to superfusion with
      nicardipine. Two types of channels (2.8 and 21 pS, in 110 mM BaCl2) were shown to
      have a BAY K 8644 sensitivity. The large conductance channels were L-type
      channels. The smaller events were elicited at more hyperpolarized potentials (by
      some 30 mV). Their mean open time was 16 ms in control conditions. In presence of
      BAY K 8644, additional long open times were observed (up to 100 ms as compared to
      7.8 ms for the time constants of the slow mode of the L-type channel). We refer
      to these channels as SB channels: of small conductance and sensitive to BAY K
      8644. In the presence of nicardipine, SB channels are not noticeably modified, in
      contrast to the L-type openings which are abolished. Also, SB open times are
      close to control values when nicardipine is added after a BAY K 8644 application.
      We suggest that, at physiological concentrations of divalent ions, an SB-type
      activity is elicited above -40 mV which generates the low threshold sustained
      current.

PMID- 1377816
TI  - Arginine-vasopressin induces mode-2 gating in L-type Ca2+ channels (smooth muscle
      cells of the urinary bladder of the guinea-pig).
AB  - The effect of arginine-vasopressin (AVP, 0.1 microM) on elementary Ca2+ channel
      currents (L-type) was studied in cell-attached patches with 10 mM BaCl2 as the
      charge carrier. At a constant potential of -30 mV, bath applied AVP increased the
      channel openness (NPo) by a factor of 4.7 +/- 3.0 (mean +/- SD, n = 9), the
      effect resulted from an increase in the frequency of opening (factor 2.5 +/- 0.8)
      and from a longer mean open time. Under control, openings longer than 5 ms
      contributed only 4% of the total, however, with the application of AVP this
      contribution increased to 29%. Under control, the open times were distributed
      along a single exponential (tau o1 = 0.8 +/- 0.4 ms), a double exponential
      distribution was obtained during AVP (tau o1 = 0.8 +/- 0.5 ms, tau o2 = 7.5 +/-
      0.7 ms). The Ca2+ agonist BAYk8644 (1 microM) changed the open time distribution
      similarly to AVP (tau o1 = 1.0 +/- 0.5 ms, tau o2 = 9 +/- 2.8 ms). With 1 microM
      BAYk8644 in the bath, AVP did not significantly increase the relative
      contribution of long openings, however, AVP increased the frequency of openings
      by a factor of 2.0 +/- 1 (n = 6). The results are compatible with the idea that
      AVP can change the gating of L-type Ca2+ channels from mode 1 to mode 2.

PMID- 1377817
TI  - Artiodactyl retroposons: association with microsatellites and use in SINEmorph
      detection by PCR.
AB  - During a search of polymorphic microsatellites for bovine genome mapping, we
      found that microsatellites often occur as tails of artiodactyl C-A retroposon
      elements. In this element, C (85bp) is a tRNA derivative, while A (117bp) is of
      unknown origin. The A element also occurs as dimer element with a connecting 27bp
      linker sequence comprising hexanucleotide CACTTT repeats. In 10 clones (45% of
      those selected deliberately for dinucleotide repeats), the microsatellite motif
      is associated with the C-A retroposon. In 50% of 44 database artiodactyl C-A
      sequences, the element also has a microsatellite tail. The microsatellite is
      usually a simple (CA)n repeat, but in some cases it is an apparent derivative of
      the linker sequence CACTTT. All but one of 33 database dimer elements have
      trinucleotide repeat tails (AGC)n, n = 1-9. Microsatellites, retroposons, and
      their truncated versions (C and/or A) often occur as clusters. We derived the
      consensus sequence (202bp) of the C-A element, and designed four primers for
      inter-SINE amplification with the aim of finding SINEmorph polymorphisms. The
      method is potentially powerful for rapidly producing polymorphic markers for
      artiodactyl genome mapping.

PMID- 1377818
TI  - Molecular cloning of two C/EBP-related proteins that bind to the promoter and the
      enhancer of the alpha 1-fetoprotein gene. Further analysis of C/EBP beta and
      C/EBP gamma.
AB  - In an attempt to identify proteins that may regulate alpha 1-fetoprotein (AFP)
      gene expression, we screened a cDNA expression library from neonatal rat liver
      with two essential cis-elements of the AFP promoter and enhancer. We isolated two
      cDNAs which were found to correspond to leucine zipper proteins of the CC
      AAT/enhancer binding protein (C/EBP) family: C/EBP beta and C/EBP gamma. The
      three related proteins C/EBP alpha, beta and gamma bind with indistinguishable
      specificity to multiple DNA sites in the promoter and the enhancer of the AFP
      gene. In addition, C/EBP beta and C/EBP gamma readily heterodimerize with each
      other as well as with C/EBP alpha. The mRNAs coding for C/EBP beta and C/EBP
      gamma are expressed in a wider variety of rat tissues than C/EBP alpha mRNA,
      including yolk sac and fetal liver. The steady-state levels of C/EBP alpha, beta
      and gamma mRNAs increase during liver development, in parallel with their
      respective gene transcriptional rates. The high levels of C/EBP beta and gamma
      mRNAs in rat yolk sac and fetal liver, where C/EBP alpha is poorly expressed,
      suggest that C/EBP beta and/or gamma could be preponderant or early regulators of
      the AFP gene in these tissues.

PMID- 1377819
TI  - Novel mutants of 23S RNA: characterization of functional properties.
AB  - Single point mutations corresponding to the positions G2505 and G2583 have been
      constructed in the gene encoding E.coli 23S rRNA. These mutations were linked to
      the second mutation A1067 to T, known to confer resistance to thiostrepton (1).
      Mutant ribosomes were analyzed in vitro for their ability to direct poly(U)
      dependent translation, their missence error frequency and in addition their
      sensitivity to peptidyltransferase inhibitors. It was evident that the mutated
      ribosomes had an altered dependence on [Mg2+] and an increased sensitivity to
      chloramphenicol during poly(U) directed poly(Phe) synthesis. In a
      transpeptidation assay mutated ribosomes were as sensitive to chloramphenicol as
      wild-type ribosomes. However, the mutant ribosomes exhibited an increased
      sensitivity to lincomycin. An increase in translational accuracy was attributed
      to the mutations at the position 2583: accuracy increased in the order G less
      than A less than U less than C.

PMID- 1377821
TI  - Release of calcitonin gene-related peptide and tachykinins from the rat trachea.
AB  - The release of calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and
      substance P (SP) from intralumenally perfused rat trachea was examined in vitro.
      In accord with the relative tissue levels of the respective peptides, capsaicin
      (10(-8) to 10(-5) M) and K+ (120 mM) added to the perfusate resulted in a
      concentration-dependent increase in the levels of CGRP and NKA, and to a minor
      extent SP, in the perfusates. Sequential exposure of the trachea to capsaicin
      revealed a concentration-dependent tachyphylaxis of CGRP release. Thus, 40 min
      after the application with capsaicin 10(-5) M, a second exposure to capsaicin at
      the same concentration, or K+ 120 mM, did not evoke CGRP release. In contrast,
      prior stimulation with K+ 120 mM significantly enhanced the CGRP release induced
      by a second stimulation with K+ 120 mM or capsaicin 10(-5) M. Capsaicin- and K(+)
      induced peptide release was diminished or abolished in the absence of Ca2+. HPLC
      analysis of CGRP in release materials revealed that there was a single peak which
      eluted in the same fraction as synthetic rat CGRP. These data demonstrate that
      CGRP, NKA and SP exist in releasable, capsaicin-sensitive pools in terminals
      which lie within the proximal lumen of the trachea.

PMID- 1377820
TI  - Expression of the human cystic fibrosis transmembrane conductance regulator gene
      in the mouse lung after in vivo intratracheal plasmid-mediated gene transfer.
AB  - As an approach to gene therapy for the respiratory manifestations of cystic
      fibrosis (CF), in vivo plasmid-mediated direct transfer of the normal CF
      transmembrane conductance regulator (CFTR) gene to the airway epithelium was
      investigated in mice. To evaluate the feasibility of this strategy, pRSVL, a
      plasmid composed of a firefly luciferase gene driven by the Rous sarcoma virus
      long terminal repeat (RSV-LTR), along with cationic liposomes was instilled into
      the trachea of C57BI/6NCR mice. With administration of 200-400 micrograms plasmid
      DNA, luciferase expression could be detected in the mouse lung homogenates for at
      least 4 wk. With this background, a CFTR expression plasmid vector (pRSVCFTR)
      constructed by replacing the luciferase cDNA from pRSVL with the normal human
      CFTR cDNA was evaluated in vivo in mice. Intratracheal instillation of pRSVCFTR
      with cationic liposomes followed by analysis of mouse lung RNA by polymerase
      chain reaction amplification (after conversion of mRNA to cDNA) using a RSV-LTR
      specific sense primer and a human CFTR-specific antisense primer demonstrated
      human CFTR mRNA transcripts from one day to 4 wk after instillation. Further, in
      vivo evaluation of beta-galactosidase activity after intratracheal administration
      of an E. coli lacZ gene expression plasmid vector directed by the cytomegalovirus
      promoter (pCMV beta) demonstrated that the airway epithelium was the major target
      of transfer and expression of the exogenous gene. These observations demonstrate
      successful plasmid-mediated gene transfer to the airway epithelium in vivo. This
      strategy may be feasible as a form of gene therapy to prevent the pulmonary
      manifestations of CF.

PMID- 1377822
TI  - Substance P inactivation by transglutaminase in vitro.
AB  - Gamma(glutamyl5)spermine derivative of substance P (Spm-SP) was synthesized in
      vitro in the presence of purified guinea pig liver transglutaminase and Ca2+. The
      spermine adduct of the neuropeptide was purified by HPLC on a reversed-phase
      column and characterized by fast atom bombardment mass spectrometry. The
      biological activities of Spm-SP were tested by assaying, in comparison with
      substance P, its ability to induce both the contractions of smooth muscle in
      vitro and the edema formation in vivo. Spm-SP was shown not to elicit contractile
      responses in the isolated rat stomach strip and duodenum and not to antagonize
      the spasmogenic effect evoked by the native neuropeptide. Furthermore, Spm-SP was
      unable, when administered into rats by plantar injection, either to provoke an
      acute inflammatory response in the hind limb or to antagonize the edema formation
      induced by a concurrent administration of substance P. These results indicate
      that the introduction of a large size hydrophilic moiety at the glutamine5 level
      negatively affects the ability of the neuropeptide to bind to its receptor(s),
      thus supporting the view that the hydrophobic middle portion of substance P plays
      a key role in receptor recognition.

PMID- 1377824
TI  - Isolation, purification and biochemical characterization of human placental
      interferons by tandem high-performance affinity chromatography.
AB  - Human placental trophoblasts, fibroblasts and the trophoblast-derived malignant
      cell JAR are potent producers of interferons (IFNs) when stimulated with Sendai
      virus. The three cell lines produced different levels and compositions of IFN
      alpha subtypes and IFN-beta. Anti-IFN globulins, Cibacron Blue F3GA and
      Concanavalin A were covalently immobilized on pressure-stable, macroporous
      polymeric matrices derivatized with vinyl sulphone (HEMA-BIO 1000 VS and HEMA
      1000 VS). These supports were packed in biocompatible PEEK columns and were
      coupled with switching valves, to develop a tandem high-performance affinity
      chromatographic (HPAC) method for the isolation, purification and biochemical
      characterization of the IFNs produced in Sendai virus-stimulated human placental
      trophoblasts, fibroblasts and trophoblast-derived malignant cell, JAR, cultures.
      Silver-stained SDS-PAGE and gel densitometric analysis revealed the purity of the
      purified proteins to be between 94 and 98%. Specific activities of the purified
      IFNs ranged between 0.37-2.76 x 10(8) IU/mg of protein with cumulative recoveries
      between 90 and 92.2%. The purified IFN components exhibited quantitatively
      different antiviral activities in human and bovine cell lines. The utility of the
      tandem method for the purification and characterization of human type 1 IFNs
      produced from other cell lines are also discussed.

PMID- 1377823
TI  - Tissue distribution and innervation pattern of peptide immunoreactivities in the
      rat pancreas.
AB  - The distribution of calcitonin gene-related peptide (CGRP), substance
      P/tachykinin (SP/TK), vasoactive intestinal polypeptide (VIP), neuropeptide Y
      (NPY) and gastrin-releasing peptide (GRP) immunreactivities (IR) in the rat
      pancreas was investigated using radioimmunoassay and immunohistochemistry. CGRP,
      NPY and VIP tissue contents are much higher than GRP and SP/TK concentrations.
      Peptide-containing nerves are distributed to both the exocrine and endocrine
      pancreas. However, differences exist in terms of density and targets of
      innervation for each peptidergic system. In the acini and through the stroma,
      fibers IR for CGRP, NPY and VIP are greater than GRP- and SP/TK-containing
      processes. The vasculature is supplied by a prominent NPY, CGRP and, to a lesser
      extent, SP/TK innervation. VIP-IR is found occasionally, and GRP-IR is never
      detected, in fibers associated with blood vessels. Around ducts, CGRP- and NPY
      positive neurites are greater than SP/TK- greater than or equal to VIP-IR fibers,
      whereas GRP-containing nerves are not visualized. In the islets, the density of
      peptidergic nerves is: VIP-, GRP- greater than or equal to CGRP-IR greater than
      NPY or SP/TK. In intrapancreatic ganglia. VIP- and, to a lesser extent, NPY-IRs
      are found in numerous neuronal cell bodies and in nerve fibers; GRP-IR is present
      in numerous nerve processes and in few cell bodies; CGRP- and SP/TK-IRs are
      detected only in fibers wrapping around unlabeled ganglion cells. The majority of
      CGRP-IR fibers contain SP/TK-IR. The existence of differential patterns of
      peptidergic nerves suggests that peptides exert their effects on pancreatic
      functions via different pathways.

PMID- 1377825
TI  - Detection of local structures in reduced unfolded bovine pancreatic trypsin
      inhibitor.
AB  - The structure of BPTI and reduced BPTI in concentrated guanidinium HCl (GUHCl) in
      the presence of glycerol has been probed by measurements of dynamic nonradiative
      excitation energy transfer between probes attached to its amino groups.
      Interprobe distance distributions were obtained from analysis of donor
      fluorescence decay curves and used to characterize local structures in unordered
      states of the protein. Site specifically fluorescently labeled BPTI derivatives
      (1-n)BPTI (n = 15, 20, 41, 46) were used, each carrying a 2-methoxy-naphthyl-1
      methylenyl group (MNA) at the N-terminal amino group of arg1 and 7
      (dimethylamino)-coumarin-4-yl-acetyl residue (DA-coum) at one of its epsilon-NH2
      groups of the lysine side chains. Analysis of donor fluorescence decay kinetics
      gave the interprobe distance distributions in the native and denatured states.
      The N-terminal-segment, residues 1-15, is in an extended conformation (with an
      average interprobe distance of 34 +/- 2 A) in the native state. Upon unfolding by
      reduction with DTT or beta-mercapto ethanol in 6 M GUHCl/glycerol mixture, the
      conformation of this segment relaxed to a state characterized by a reduced
      average interprobe distance and a larger width of the distances distribution. The
      average distance between residues 1 and 26, i.e., between the N-terminus and the
      turn of the twisted beta sheet element (residues 18-35), increased upon
      unfolding. At -30 degrees C in the above solvent, the distribution between these
      two sites was probably composed of two conformational subpopulations. About 45 +/
      20% of the molecules were characterized by a short interprobe distance (like the
      native state) representing a compact conformation, and 55 +/- 20% of the
      molecules showed large interprobe distances representing an expanded (unfolded)
      conformation. Thus local structures seem to exist in reduced denatured BPTI even
      under denaturing conditions in 6 M GUHCl/glycerol mixtures. Some of those
      structures are unstable in guanidinium isothiocyanate (GUSCN). The method
      introduced here is suitable for probing local structures and very long range
      interactions in unfolded proteins and for search for folding initiation sites
      (FISs) and early folding intermediates.

PMID- 1377826
TI  - Mutating the charged residues in the binding pocket of cellular retinoic acid
      binding protein simultaneously reduces its binding affinity to retinoic acid and
      increases its thermostability.
AB  - Three-dimensional modeling of the complex between retinoic acid-binding protein
      (CRABP) and retinoic acid suggests that binding of the ligand is mediated by
      interaction between the carboxyl group of retinoic acid and two charged amino
      acids (Arg-111 and Arg-131) whose side chains project into the barrel of the
      protein. To assess the contribution of these amino acids to protein-ligand
      interaction, amino acid substitutions were made by oligonucleotide-directed, site
      specific mutagenesis. The wild-type and mutant proteins were expressed in E. coli
      and subsequently purified. Like wild-type CRABP, the mutant proteins are composed
      mainly of beta-strands as determined by circular dichroism in the presence and
      absence of ligand, and thus presumably are folded into the same compact barrel
      structure as the wild-type protein. Mutants in which Arg-111 and Arg-131 are
      replaced by glutamine bind retinoic acid with significantly lower affinity than
      the wild-type protein, arguing that these two residues indeed interact with the
      ligand. The mutant proteins are more resistant to thermal denaturation than wild
      type CRABP in the absence of retinoic acid, but they are not as thermostable as
      the CRABP-retinoic acid complex. These data suggest a model for CRABP-retinoic
      acid interaction in which the repulsive forces between the positively-charged
      arginine residues provide conformational flexibility to the native protein for
      retinoic acid to enter the binding pocket. Elimination of the positively-charged
      pair of amino acids produces a protein that is more thermostable than wild-type
      CRABP but less effective at ligand-binding.

PMID- 1377827
TI  - Effects of nimodipine on biogenic amines in discrete brain areas.
AB  - Discrete brain sections were obtained from rats after once or repeatedly given
      intraperitoneal nimodipine at doses ranging from 2.5 to 40 mg/kg. The single or
      the last treatment was carried out at 2-8 h before killing. The biogenic amine
      and metabolite content of the tissue samples were determined by high-performance
      liquid chromatography with electrochemical detection. The nimodipine-induced
      effects, chiefly regarding the brainstem, the thalamus-midbrain and the striatum,
      consisted of both an increase in 5-hydroxyindoleacetic acid (5-HIAA) levels and a
      decrease in dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)
      levels. Since the 5-HIAA/5-hydroxytryptamine (5-HT) ratio was increased, whereas
      the DOPAC/dopamine (DA) and HVA/DA ratios were decreased, it was argued that
      nimodipine activated the serotonergic and inhibited the dopaminergic systems. The
      first effect was enhanced by fasting and, likewise, by drug administration
      repeated for 5 days, while the second was not affected by fasting, but
      disappeared after 5 days' treatment. The data obtained appeared to substantiate
      the usefulness of nimodipine to treat some disorders of the central nervous
      system.

PMID- 1377828
TI  - Ataxia telangiectasia in the British Isles: the clinical and laboratory features
      of 70 affected individuals.
AB  - Seventy individuals with ataxia telangiectasia were studied: 29 females and 41
      males with an age range of 2 to 42 years. The majority (43/68) presented by 3
      years of age with truncal ataxia. All had progressive, handicapping neurological
      symptoms exhibiting ataxia (70/70), ocular motor apraxia (70/70), an impassive
      face (70/70), dysarthria (70/70), chorea (68/70), dystonia (55/70) and peripheral
      neuropathy (50/70). Clinical immune deficiency was present in 43 of 70 patients.
      Ocular telangiectasia were seen in all but one case and excessive thinness in 54
      of 70. The mean age of loss of walking was 10 years and of writing 8 years. All
      60 tested showed increased sensitivity to ionizing irradiation, 43 of 48 had an
      elevated alpha-fetoprotein level and 14 of 21 had an immunoglobulin deficiency.
      Although there was a marked variation in disease findings sibs were always
      similar. The heterogeneity seen seems at odds with the unilocus linkage of ataxia
      telangiectasia to 11q23.

PMID- 1377829
TI  - Factors predictive of completion of treatment and survival after palliative
      radiation therapy.
AB  - Ninety-seven patients who underwent radiation treatment for metastatic carcinomas
      and sarcomas were evaluated to define prognostic factors that may reliably help
      determine survival and probability of completing a course of palliative radiation
      therapy. Actuarial and logistic models were used for analysis. Predictor
      variables included age; sex; symptoms; primary site of disease; pathologic
      diagnosis; prior metastatic disease, treatment, and response; solitary versus
      multiple metastatic sites; location of metastasis; status of primary lesion;
      interval between initial diagnosis and treatment for metastatic disease; and
      Karnofsky performance score (KPS). The interval between primary diagnosis and
      metastatic treatment, and KPS, were significant variables for 22 patients (23%)
      who failed to complete their planned radiation treatment. KPS was consistently
      significant for probability of survival at 2-, 4-, 8-, and 16-month intervals. At
      8 months and 16 months, site of primary disease was significant, and at 16
      months, solitary site of metastasis was also significant. Conventional factors,
      especially KPS, are useful in predicting the likelihood of completing radiation
      therapy and of subsequent survival for patients undergoing palliative treatment.

PMID- 1377830
TI  - Changes in serum and salivary amylase during radiotherapy for head and neck
      cancer: a comparison of conventionally fractionated radiotherapy with CHART.
AB  - The changes in serum amylase that occur when radiotherapy is given in the
      treatment of head and neck cancer has been studied in 41 patients, 29 treated by
      CHART and 12 by conventionally fractionated radiotherapy. The peak rise in serum
      amylase following the start of treatment is seen earlier and is greater in the
      patients receiving continuous hyperfractionated accelerated radiotherapy (CHART).
      The serum amylase returns to normal earlier in the CHART patients so that the
      area under the curve is the same for both groups. The difference probably
      reflects the more rapid delivery of treatment to the patients receiving CHART. A
      close correlation between the peak rise in serum amylase and the amount of
      parotid tissue in the treatment volume is demonstrated. For six patients the
      total amount of amylase secreted by the parotid gland during CHART was measured
      and found to decline rapidly within a few days of the start of radiotherapy. The
      rise in serum amylase that results from the irradiation of salivary tissue
      provides a unique biochemical measure of an early radiation effect in a normal
      tissue. This probably reflects the interphase cell death of serous salivary
      cells. Although these immediate changes are of considerable interest they may not
      relate to the late effects of radiation on salivary gland function.

PMID- 1377831
TI  - Pulmonary toxicity and acute respiratory failure associated with fludarabine
      monophosphate.

PMID- 1377832
TI  - [Adenoma of the prostate (benign hypertrophy of the prostate). Diagnosis,
      development, prognosis, principles of the treatment].

PMID- 1377834
TI  - A neurodevelopmental approach to the classification of schizophrenia.
AB  - The conventional distinction between schizophrenia and manic depression has
      received little objective support from recent studies of phenomenology, outcome,
      or familial homotypy. Instead, much clinical, epidemiological, and morphological
      evidence suggests that within the broad range of Schneiderian schizophrenia there
      exists one form (congenital schizophrenia) that can be distinguished from other
      types, the manifestations of which are confined to adult life. We hypothesize
      that congenital schizophrenia is a consequence of aberrant brain development
      during fetal and neonatal life. Such patients show structural brain changes and
      cognitive impairment, and in their male predominance, early onset, and poor
      outcome, they reflect Kraepelin's original description of dementia praecox. We
      contend that adult-onset schizophrenia is itself heterogeneous. One important
      component is a relapsing and remitting disorder that is more frequent in females
      than in males, exhibits positive but not negative symptoms, and has much in
      common etiologically with affective psychosis. There also exists a very-late
      onset group in which degenerative brain disorder is implicated.

PMID- 1377833
TI  - The significance of age of onset for schizophrenia.
AB  - Age of onset is the single most important characteristic of schizophrenia that
      could yield clues to its origin. To identify the age of onset, however, the onset
      of the pathological process must be determined. This process may have more than
      one component occurring at distinctly different times in the life of an
      individual. Nevertheless, many studies, using either the first appearance of
      psychosis or the age of first hospitalization, have found gender, familial, and
      other "age of onset" differences among patients with schizophrenia. These
      differences may aid in examining genetic mechanisms for schizophrenia.

PMID- 1377835
TI  - Biologists trace the evolution of molecules.

PMID- 1377836
TI  - [Cation channels formed in lipid bilayer by Pinellia ternata lectin].
AB  - Pinellia ternata lectin (PTL), a protein exhibiting hemagglutination activity and
      carbohydrate binding specificity to mannan was purified from rhizome of Pinellia
      ternata. In this work the actions of PTL on artificial lipid bilayer were
      investigated by means of the two-compartment system of Mueller and Rudin. The
      lipid bilayer with resistance more than 10G omega was formed by a solution of
      lecithin and cholesterol (20 mg/ml and 5 mg/ml respectively) in N-decane. The
      electrical properties of the lipid bilayer were investigated in voltage clamp
      mode. Several minutes after the addition of PTL (2 micrograms/ml) in one
      compartment the channel-like noise as well as a decrease of the resistance of the
      bilayer were observed. These actions were inhibited by mannan significantly. The
      resistance increase of the bilayer with PTL-channels could be observed from 2G
      omega to control level (greater than or equal to 10 G omega) immediately after
      addition of 40 micrograms/ml mannan. The discrete conduction steps were recorded
      at low concentration of PTL and at low holding potential. The predominant unit
      conductance was 35pS in symmetric KCl solution of 100 mmol/L. The selectivity of
      PTL-channel was estimated from Goldman-Hodgkin-Katz equation by measurement of
      the reversal potential in an asymmetrical salt solution. The results showed that
      PTL-channels were cation selective.

PMID- 1377837
TI  - [On the relation between substance P and physostigmine on cardiovascular control
      in rabbit brain].
AB  - Using an electromagnetic flowmeter technique, the cardiac output as measured by
      blood flow in the aortic arch was measured during intracerebroventricular
      injection (icv.) of Substance P (SP) and physostigmine in 47 anesthetized
      rabbits. Carotid artery blood pressure and heart rate were recorded. After icv of
      SP (20 micrograms/20 microliters) or physostigmine (60 micrograms/20
      microliters), both cardiac output and mean artery pressure were increased.
      Pretreatment with icv. of atropine (150 micrograms/20 microliters) did not alter
      the effect of SP, but the effect of physostigmine was blocked by pretreatment
      with SP blocker (25 micrograms/20 microliters). These findings suggest that
      cerebral SP is involved in cholinergic mechanisms on the central control of blood
      pressure.

PMID- 1377838
TI  - Enteral nutrition with supplemental arginine, RNA, and omega-3 fatty acids in
      patients after operation: immunologic, metabolic, and clinical outcome.
AB  - The individual nutrients arginine, RNA, and omega-3 fatty acids improve immune
      function, but prospective trials have not demonstrated their effects on clinical
      outcome. Patients (n = 85) who underwent operation for upper gastrointestinal
      malignancies were randomized to receive the supplemental diet or a standard
      enteral diet after surgery. Clinical patient characteristics were similar between
      the two groups. Mean caloric intakes (1421 vs 1285 kcal/day) were similar between
      groups. Mean nitrogen intakes (15.6 vs 9.0 gm/day) and nitrogen balances (-2.2 vs
      -6.6 gm/day) measured in the first 20 patients were significantly greater in the
      supplemented group than in the standard group (p = 0.05). In vitro lymphocyte
      mitogenesis was measured in the first 31 patients and was decreased on
      postoperative day 1 in both groups, but normal levels were regained only in the
      supplemented group. In the cohort of 77 eligible patients, infectious and wound
      complications occurred significantly less often (11% vs 37%) in the supplemented
      group than in the standard group (p = 0.02). Linear logistic models for
      infectious/wound complications with control for the amount of nitrogen suggested
      (p = 0.10) dietary treatment as the major factor. Mean length of stay in the
      hospital was significantly shorter (p = 0.01) for the supplemented group (15.8 +/
      5.1 days) than for the standard group (20.2 +/- 9.4 days). These results suggest
      that postoperative enteral nutrition with supplemental arginine, RNA, and omega-3
      fatty acids instead of a standard enteral diet significantly improved
      immunologic, metabolic, and clinical outcomes in patients with upper
      gastrointestinal malignancies who were undergoing major elective surgery.

PMID- 1377839
TI  - [Hepatitis serology: use and interpretation].
AB  - Presently five viruses causing hepatitis are known, the hepatitis viruses A
      (HAV), B (HBV), C (HCV), D (HDV) and E (HEV). The genomic structure is known of
      most of all these viruses as well as some of their structural and regulatory gene
      products. Using radio- and enzyme immunoassays viral antigens can be detected for
      HBV and HDV as well as specific antibodies against all the five viruses. The
      results of these tests are the basis for the diagnosis and the follow-up of these
      infections but differ in their accuracy for each given virus. Concerning HIV one
      can differentiate between an ongoing or recently passed infection and immunity.
      Concerning HBV (and HDV), an ongoing infection at various stages can be
      distinguished from immunity. Such distinctions are not possible with respect to
      HCV except when also applying the expensive and cumbersome method of the
      polymerase chain reaction. In this paper the most important characteristics of
      the hepatitis viruses are given and the behaviour of the various viral markers
      during the infections and their consequences are described.

PMID- 1377840
TI  - [Interferon treatment of chronic viral hepatitis].
AB  - The interferon treatment of chronic viral hepatitis leads to a measurable
      inhibition of replication of the various hepatitis viruses. In adult patients
      with chronic HBe-Ag-positive hepatitis B, the seroconversion rate is tripled by
      therapy when compared with untreated controls. In chronic hepatitis C,
      biochemical remission is achieved in about 50% of patients, but there is a high
      tendency to relapse. Interferon treatment has little effect in hepatitis B virus
      infection transmitted perinatally and in chronic delta hepatitis. Better
      knowledge of prognostic variables and deeper insights into the mechanisms of
      chronic hepatitis C virus infection should help both to increase rates and
      duration of remissions and to reduce the rates of relapse in the future.

PMID- 1377841
TI  - [Palliative treatment of liver tumors].
AB  - Metastases of extrahepatic primaries are the most prevalent cause of malignant
      cells found in the liver. This overview is focusing on different regional and
      systemic palliative treatment modalities according to the histology of the
      primary tumor with special emphasis on metastastic colonic cancer. Furthermore
      indications and contraindications of the various treatment options are discussed.

PMID- 1377843
TI  - The treatment of myxoedema with raw sheep thyroid gland and its introduction into
      practice in County Londonderry in 1892.

PMID- 1377842
TI  - Surgical palliation of proximal malignant biliary obstruction.

PMID- 1377844
TI  - Cutaneous ureterostomy in adults.
AB  - In the patient with metastatic carcinoma, urinary diversion is usually achieved
      with indwelling ureteral stents or placement of a percutaneous nephrostomy tube.
      Most forms of surgical diversion carry an unacceptable morbidity rate, especially
      in the debilitated patient. Over a fifteen-year period (1974-1989), 29 adult
      patients with pelvic malignancy (32 ureters) underwent palliative cutaneous
      ureterostomy. This previously reported technique involves transverse nephropexy
      and construction of a stoma using a small skin flap. Indications included
      ureteral obstruction or severe urinary tract symptoms. Hydroureter, often
      considered a precondition for this procedure, was not present in several patients
      and was not a prerequisite to success. Complications related to the procedure
      included one postoperative death due to stroke, one death due to uremia and
      sepsis, and one instance of severe renal arterial stenosis resulting in renal
      failure. Preservation of renal function was possible in the 10 patients known to
      have survived from one to thirteen years postoperatively; only 3 patients
      eventually required stomal revision. By adherence to the surgical techniques
      described, the usually high incidence of stomal stenosis was avoided. Our
      experience reveals that although the indications for cutaneous ureterostomy are
      limited, this procedure can provide an alternative to permanent nephrostomy
      drainage or to a higher risk intestinal urinary diversion in carefully selected
      patients with a reasonable life expectancy.

PMID- 1377846
TI  - Pulmonary embolism from left subclavian vein thrombus following suprapubic
      prostatectomy.
AB  - Deep venous thrombosis (DVT) of the axillary and subclavian veins accounts for
      approximately 1-2 percent of all recorded deep venous thrombosis. Pulmonary
      embolism from an upper extremity DVT has been reported to vary between 2 percent
      and 35.7 percent. We report the occurrence of a left subclavian vein DVT with
      subsequent nonfatal pulmonary embolism in a sixty-two-year-old patient twenty
      four hours following suprapubic prostatectomy. A review of the literature is
      presented, along with pathophysiology, diagnosis, and treatment.

PMID- 1377845
TI  - Guided brachytherapy for treatment of confined prostate cancer.
AB  - A total of 133 patients underwent transperineal ultrasound-guided iodine 125 seed
      implantation for Stages A and B prostate cancer with a twenty-seven-month follow
      up. There has been no mortality and our morbidity is no more than experienced
      after transurethral resection of the prostate. By using a Mick applicator our
      operating time is well under one hour, and our patients go home the same day
      without a Foley catheter. Our results indicate that patients with PSA values of
      less than 20 ng/mL (Yang method) and/or Gleason scores of 6 or less are excellent
      candidates for brachytherapy. By subdividing the percentage of normal PSA values
      in the follow-up periods according to the patient's original PSA value, further
      credence is given to the PSA value as a strong aid in staging when the Gleason
      score is 6 or less. Although the follow-up at twenty-seven months is small, our
      preliminary results indicate that brachytherapy is a viable option to radical
      surgery in those patients who are not good candidates for surgery or who prefer
      nonsurgical treatment.

PMID- 1377847
TI  - Response to second-line hormonal manipulation monitored by serum PSA in stage D2
      prostate carcinoma.
AB  - Changes in prostate-specific antigen (PSA) have been demonstrated to accurately
      assess response to initial hormone deprivation in metastatic prostate cancer
      patients. The role of PSA in monitoring response to second-line hormonal
      treatment has not been documented. In a group of 20 patients with an initial
      response to androgen deprivation and subsequent relapse, we monitored PSA levels
      before and after second-line therapy. Ten patients had a clinical response. Four
      had a more than 90 percent decrease in serum PSA compared with the level at
      initial progression. This clinical response was maintained for a mean of eighteen
      months. Six patients had a PSA decrease less than 90 percent; their clinical
      response was of a mean 5.5 months. Ten patients had no change or increase in PSA.
      Seven had no clinical response, and 3 responded for an average of four months.
      Although production of PSA might be under endocrine control, changes in PSA are
      useful for monitoring response to second-line hormonal therapy.

PMID- 1377848
TI  - Intrathecal administration of substance P in the rat: the effect on bladder and
      urethral sphincteric activity.
AB  - At the lumbosacral spinal cord level in the rat, substance P-positive neurons are
      present in dense concentration in the dorsal horn and the sacral parasympathetic
      nucleus. We undertook the present study to investigate the effect of intrathecal
      substance P (10 micrograms at the L6-S1 level) on urinary bladder and urethral
      sphincteric activity and to compare these effects with those of intravenous and
      intra-arterial administration. Three different bladder pressure responses were
      triggered by intrathecal substance P: (A) an immediate, strong bladder
      contraction (n = 5); (B) augmentation of the micturition reflex, as indicated by
      strong detrusor contractions in response to intravesical saline perfusion (n =
      4); and (C) a slow, gradual increase to a high, steady peak (n = 8). The
      sphincteric electromyographic (EMG) activity was consistently increased. When
      substance P was given intravenously (n = 10) and intra-arterially (n = 3), the
      form, duration, and maximal amplitude of bladder contractions (owing to a direct
      smooth-muscle action) were comparable with those of Group A. The effects in
      intrathecal Groups B and C suggest that substance P provides a tonic influence on
      motor horn cells and on the preganglionic neurons in the sacral parasympathetic
      nucleus at the lumbosacral spinal cord level, where neuronal circuits controlling
      bladder and sphincteric activity are located.

PMID- 1377849
TI  - Canine pericardial mesothelioma.

PMID- 1377850
TI  - [Combined surgical-interventional procedure in congenital heart defects with
      postoperative, left ventricular dysfunction].
AB  - Creation of a communication between the left and right atrium to decompress the
      left ventricle can be life-saving after corrective surgery in some patients with
      congenital heart disease and small left ventricle. After adaptation of the left
      ventricle, surgical closure of this anastomosis becomes mandatory. We report four
      patients (2.9 to 8.2 kg) where non-surgical, transcatheter-closure was performed
      in the first year of life using the Rashkind-PDA-Occluder System (USCI). In a
      newborn with d-transposition of the great arteries (2.9 kg), in a patient with
      atrial septal defect (5.1 kg), and in a patient with tetralogy of Fallot with
      atrial septal defect (4.9 kg) atrial septal defects were not completely closed
      during correction because of left-ventricular dysfunction. Five to 12 days
      postoperatively transcatheter closure was performed utilizing the 8F-Rashkind-PDA
      Occluder System in the first two patients (2.9 kg and 4.9 kg) and by use of the
      11F-Rashkind-PDA-Occluder System in the third patient (4.9 kg). In the patient
      with supracardiac total anomalous pulmonary venous drainage via a vertical vein,
      the vertical vein was not closed during surgical correction at the age of 2
      months. Transcatheter closure was performed 6 months later using the 11F-Rashkind
      PDA-Occluder-System. It is concluded that small, defined atrial septal defects
      can be closed, even in newborns, using the Rashkind-PDA-Occluder System (USCI)
      and, furthermore, that large vessels, even without luminal narrowing can be
      occluded completely. Thus, this combined "surgical-interventional approach" is
      not limited by age and could reduce the risk of surgical correction in patients
      with congenital heart disease and small left ventricle.

PMID- 1377852
TI  - [Neo-angiogenesis after transplantation of a free skeletal muscle flap to the
      myocardium of the dog].
AB  - For the study of the process of neovascularization the effects of the
      transplantation of a free skeletal muscle flap on the heart of the dog were
      studied. For this purpose, in 14 mongrel dogs a myocardial infarction of the
      anterior wall of the heart was produced by the selective injection of
      microspheres into the left anterior descending artery. In 12 of those, on the
      area of infarction 4 weeks later a free pectoralis muscle flap was transplanted
      with its pars anterior in contact with the myocardium (group A). The arterial
      anastomosis was achieved with the internal mammary artery, the venous flow
      directed into the right atrium. In 2 other dogs (group B) the pectoralis flap was
      transplanted with irt pars anterior on a healthy myocardium. In 2 further dogs
      (group C) the pectoralis flap was transplanted on a infarcted myocardium with its
      pars posterior, i.e. the muscle fascia interponed. 16 weeks later a
      microcorrosion-cast-preparation and histological examinations showed in group A
      and B a prominent capillary network penetrating from the muscle into the
      myocardium, whereas in group C the muscle fascia inhibited this process. Thus,
      for the process of neovascularization the "bloody" contact between a skeletal
      muscle graft and the myocardium is necessary. Results are discussed with regard
      to possible factors inducing neoangiogenesis.

PMID- 1377851
TI  - Effect of adjuvant formulations on the selection of B-cell epitopes expressed by
      a malaria peptide vaccine.
AB  - Because subunit vaccines may create artificial epitopes, the goal of this study
      was to concentrate the immune response toward protective epitopes contained in a
      peptide, [(NAGG)5]Y. This peptide consisted of five repeat sequences of the
      immunodominant epitope of the circumsporozoite protein of the simian malaria
      parasite Plasmodium cynomolgi and a terminal tyrosine. It was conjugated to
      bovine serum albumin and mixed with various adjuvant formulations, including
      block copolymers L121, L141, L180.5 and a lipopolysaccharide (LPS). Outbred mice
      were vaccinated with seven vaccine formulations. Postvaccination sera from each
      group of mice were then pooled, and antibody responses against peptide [(NAGG)5]Y
      or (NAGG)5 were tested in an enzyme-linked immunosorbent assay and against
      sporozoites of P. cynomolgi in an indirect fluorescent antibody assay. Although
      all groups elicited a high antibody response to the peptide [(NAGG)5Y], the
      presence of the tyrosine induced a different antibody response to the peptide
      (NAGG)5, and formulations containing LPS alone did not induce an antibody
      response to either (NAGG)5 or P. cynomolgi sporozoites. The formulation including
      both LPS and the copolymer L121 was the only one to inhibit the development of P.
      cynomolgi sporozoites in rhesus monkey hepatocytes by 50%. These results suggest
      that vaccine formulations influence B-cell epitope selection.

PMID- 1377853
TI  - Insulin-like growth factor binding protein-3 in normal pubertal girls.
AB  - IGFBP-3 concentrations rise in the second decade of life. To test the hypothesis
      that the stage of pubertal development, independent of chronological age, was
      associated with these increases we measured serum IGFBP-3 concentrations by
      radioimmunoassay in 324 sixth and seventh grade girls (12.3 +/- 0.7 years) at the
      beginning of a multisite school-based health curriculum. The mean (+/- SD) serum
      IGFBP-3 among the 242 girls with complete data was 4.0 +/- 0.7 mg/l. Pubertal
      stage was significantly associated with IGFBP-3 (p less than 0.0001, ANOVA). Mean
      concentrations rose from 3.5 +/- 0.7 mg/l among those with the earliest pubertal
      stages to 4.2 +/- 0.7 mg/l among the mature girls. IGF-I and IGFBP-3
      concentrations were significantly correlated (Spearman's r = 0.43, p less than
      0.0001). After controlling for the association between pubertal development and
      IGFBP-3 concentrations, only the waist/hip ratio, among the various measures of
      body composition, was significantly associated with IGFBP-3 concentration
      (Spearman's r = -0.23, p = 0.0002). Likewise, none of the measures of nutrition:
      intake of total calories, protein, fat and carbohydrate; serum iron; red cell
      mean corpuscular volume; or cholesterol; were significantly associated with IGFBP
      3 concentrations. There was, however, a small, but significant association
      between IGFBP-3 concentrations and both serum transferrin and blood hemoglobin
      concentrations. Pubertal stage has a significant impact on IGFBP-3 concentrations
      and those attempting to utilize IGFBP-3 concentrations during adolescence should
      be cognizant of the subject's pubertal stage.

PMID- 1377854
TI  - Triiodothyronine (T3) stimulates insulin-like growth factor (IGF)-1 and IGF
      binding protein (IGFBP)-2 production by rat osteoblasts in vitro.
AB  - Osteoblast-like cells prepared from neonatal rat calvariae and grown under serum
      free conditions produce IGF-1 and IGFBPs. In contrast to growth hormone, T3 and
      PTH increased both IGF-1 mRNA expression and net IGF-1 release in calvaria cells.
      In addition, they stimulated net production of IGFBP-3 and of an IGFBP with an
      apparent molecular weight of 32 kDa which was recognized by an antiserum against
      rat IGFBP-2. Bone cells expressed remarkably high levels of mRNA for IGFBP-2, the
      predominant IGFBP in serum of newborn rats. T3 at low physiological
      concentrations but not growth hormone stimulated IGFBP-2 mRNA expression and
      IGFBP-2 production in bone cells in vitro. Thus, IGFBPs are differentially
      regulated by these hormones and may play an autocrine/paracrine regulatory role
      in bone.

PMID- 1377855
TI  - Amyloid beta protein precursors with kunitz-type inhibitor domains and
      acetylcholinesterase in cerebrospinal fluid from patients with dementia of the
      Alzheimer type.
AB  - We used the ELISA to measure the concentration of amyloid protein precursor with
      Kunitz type trypsin inhibitor domains (APPI) in CSF of dementia of the Alzheimer
      type (DAT) and examined the correlation of APPI with acetylcholinesterase (AChE)
      and somatostatin (SRIF). We found the APPI concentration in CSF of DAT to be
      significantly elevated compared with that of multi-infarct dementia and controls.
      We could significantly correlate APPI with AChE, but not correlate APPI with
      SRIF. The present results suggest that measurement of CSF APPI levels may be
      useful for diagnosis of DAT and the change of APPI may closely be associated with
      abnormality of acetylcholine system in DAT that has been reported.

PMID- 1377857
TI  - Presynaptic terminal loss from alpha-motoneurones following the retrograde axonal
      transport of diphtheria toxin.
AB  - Intercostal motoneurones intoxicated following intraneural injection of
      diphtheria toxin exhibited a progressive dilatation and fragmentation of Nissl
      body rough endoplasmic reticulum (rER), coupled with two different forms of
      presynaptic terminal response. Firstly, terminal dysjunction without prior
      degeneration, and secondly, Wallerian-type degeneration. Dysjunction was
      attributed to a toxin-related failure by the motoneurones to maintain
      postsynaptic site structure. Degeneration was considered to arise from toxicity
      in presynaptic neurones, either neighbouring motoneurones or local interneurones.
      Morphometry revealed that by 8 days, intoxicated motoneurones exhibited a 33%
      loss in terminal frequency, a 15% loss in residual presynaptic membrane, and a
      43% loss in overall presynaptic input. The concomitant loss of synaptic sites was
      greater that the overall loss of presynaptic membrane, indicating a toxin-related
      deficiency of the maintenance of postsynaptic sites. Analyses of the relationship
      between changes in terminal numbers and the development of Nissl body abnormality
      in the postsynaptic motoneurone identified three groups of motoneurones: (i)
      those with normal presynaptic input and normal neuronal Nissl body rER; (ii)
      those showing a dramatic loss of presynaptic input and a marked dilatation and
      fragmentation of Nissl bodies; and (iii) neurones exhibiting a maintained or
      further loss of presynaptic input coupled with extreme dilatation and
      fragmentation of Nissl body rER with loss of Nissl body structure. These changes
      are discussed in context with the known molecular action of diphtheria toxin.

PMID- 1377858
TI  - Light microscopic response of neuronal somata, dendrites and axons to post-mortem
      concussive head injury.
AB  - Forty anesthetized rats were cooled below 3 degrees C by 30-min transcardial
      perfusion of chilled physiological saline before a concussive head injury. The
      animals were then perfusion-fixed with a buffered formaldehyde-glutaraldehyde
      solution. Another forty rats were fixed by 30-min transcardial perfusion of the
      same fixative before a similar concussive head injury. In brain sections of both
      groups of animals a new silver method stained, in a Golgi-like fashion, a number
      of neurons and long axonal segments scattered among unstained ones. The
      similarity between these findings and those obtained following in vivo concussive
      head injuries described in accompanying papers suggests that the formation of
      traumatically induced argyrophilic neuronal damage is independent of metabolic
      processes, i.e., it may be a primary morphopathological process.

PMID- 1377856
TI  - Immunocytochemical demonstration of interphotoreceptor retinoid-binding protein
      in cerebellar medulloblastoma.
AB  - Previously, immunoreactive rod-opsin and S-antigen (arrestin), two highly
      characteristic markers of retinal photoreceptors and pinealocytes, were shown to
      be present in certain medulloblastoma cells. It, thus, has been suggested that
      such cells differentiate along the photoreceptor lineage. This is corroborated in
      the present immunocytochemical investigation using antibodies against another
      photoreceptor-cell marker, the interphotoreceptor retinoid-binding protein
      (IRBP). As shown in preparations of human retina and pineal organ, IRBP can be
      successfully demonstrated in formalin-fixed and paraffin-embedded tissue: the
      IRBP immunoreaction is located to the outer and inner segments of retinal
      photoreceptor cells and to perikarya of certain pinealocytes. Examination of
      formalin-fixed, paraffin-embedded biopsy specimens of 66 cerebellar medullo
      blastomas revealed varying numbers of IRBP-immuno-reactive tumor cells in 19
      cases that were formerly shown to contain rod-opsin and S-antigen immunoreaction.
      IRBP-immunoreactive tumor cells were also found in a retinoblastoma and a
      pineocytoma, but not in neuroblastoma, ganglioneuroblastoma, glioblastoma,
      oligodendroglioma and astrocytoma. The results indicate: (1) cerebellar
      medulloblastomas are heterogeneous in their differentiation potential; (2) one
      type of medulloblastoma displays photoreceptor characteristics; (3) this type
      appears to be closely related to retinoblastoma and pineal cell tumors; and (4)
      all three types of tumors may display additional common features to be explored
      in future studies.

PMID- 1377859
TI  - Immunohistochemical analysis of spinal intradural xanthomatosis developed in a
      patient with phytosterolemia.
AB  - Multiple intradural xanthomatous tumors developed in 48-year-old female with
      familial phytosterolemia. These tumors were restricted to the spinal denticulate
      ligaments. Histological and immunohistochemical findings were fundamentally
      similar to those of tendinous xanthomas. The major cellular component of these
      tumors were identified as of mono-histiocytic origin because they possessed
      myeloid histiocytic antigen (Mac 387), CD11c and lysozyme but not CD15.
      Sitosterols, campesterols and cholestanols were recovered from the extract of the
      tumors and the lesions were confirmed to be phytosterolemic xanthomas. Schwann
      cells stained with anti-S100 protein were confined to the perivascular small
      nerve bundles and did not show xanthomatous change. Although immunohistochemical
      preparation of epithelial membrane antigen and desmoplakin I+II revealed the
      presence of non-neoplastic meningothelial cells in the superficial portion of the
      tumors, they were too few to play a significant role in the development of these
      xanthomas.

PMID- 1377860
TI  - Etiologic and pathogenetic study of mental retardation with multiple congenital
      anomalies.
AB  - Etiology and pathogenesis of MCA/MR in 1,023 patients (618 male; 405 female) with
      mental retardation were studied. Of 1,023 patients, there were 563 cases (317
      male; 246 female) with MCA (55%). Among the MCA patients, there were 303 (156
      male; 147 female) whose primary etiology was clarified (53.8%). Among the 260
      patients with MCA/MR of unknown etiology, there were 23 with recognizable
      syndromes of unknown etiology and 7 previously reported by us as possibly having
      a new malformation syndrome. We had 569 patients with mental retardation of
      unknown etiology including 263 (41.5%) who were involved with MCA.

PMID- 1377861
TI  - GC/MS analysis of urine in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency.
AB  - A patient with 3-hydroxy-3-methylglutaric aciduria was diagnosed using gas
      chromatography mass spectrometry. The patient had severe metabolic acidosis,
      hypoglycemia and hyperammonemia and excreted abnormal amounts of 3
      methylglutaconic, 3-hydroxy-3-methylglutaric, 3-methylglutaric, 3
      hydroxyisovaleric and glutaric acids in the urine. 3-Hydroxy-3-methylglutaric
      acid appeared as two peaks on the chromatogram after trimethylsilylation. One was
      a tri-trimethylsilyl and the other a di-trimethylsilyl derivative. 3
      Methylglutaconic acid appeared as three peaks: cis-, trans- and cyclic cis
      isomers. The structure of these derivatives was elucidated by deuterium-labeled
      trimethylsilyl derivatization. The di-trimethylsilyl derivative of 3-hydroxy-3
      methylglutaric acid and the cyclic cis-isomer of 3-methylglutaconic acid do not
      appear to have been previously described. After treatment with leucine
      restriction milk, the excretion of leucine catabolites decreased but 3
      methylglutaconic and 3-hydroxy-3-methylglutaric acids continued to be excreted at
      abnormally high levels. It is concluded that these two metabolites are necessary
      for the chemical diagnosis of HMG-CoA lyase deficiency. This patient is the first
      case of HMG-CoA lyase deficiency to be reported in Japan.

PMID- 1377862
TI  - Current concepts in the treatment of Turner syndrome with special reference to
      the treatment of short stature.

PMID- 1377863
TI  - Pubertal growth.

PMID- 1377864
TI  - [Current problems of benign prostatic hypertrophy].

PMID- 1377865
TI  - [Review of 36 trigono-cervico-prostatectomies, carried out for prostatic
      pathology].
AB  - Review of 36 trigone-cervix-prostatectomies, performed in our services. Studies
      made before and after the procedure. Indications for trigone-cervix
      prostatectomies. Complications and results obtained. Trigone-cervix
      prostatectomies as an alternative to prostate transurethral resection, in a
      highly selected group of patients, because of its simplicity and better results.

PMID- 1377866
TI  - [Morphological study of rubeosis iridis induced in animal eyes].
AB  - Rubeosis iridis was produced experimentally in rhesus monkey eyes, by means of
      occlusion of the major retinal vessels of the retina and persistent ocular
      hypotony. Clinically, rubeosis iridis was recognized 5 days after the procedure.
      Histopathologically, these vessels developed anteriorly to the iris surface and
      endothelial fenestrations showed evidence of iris neovascularization. Endothelial
      cells of the vessels projected toward the internal lumen and showed immaturity.
      Newly formed vessels originated from the stromal vessels in the iris. This method
      is an effective experimental model for the induction of rubeosis iridis.

PMID- 1377867
TI  - [Unique immunological properties of short forms of the interphotoreceptor
      retinoid-binding protein derived uveitogenic peptide].
AB  - Interphotoreceptor retinoid-binding protein (IRBP) induces experimental
      autoimmune uveoretinitis in a variety of animals. We have previously shown that
      sequence 1169-1191 of bovine IRBP has strong uveitogenicity and immunogenicity in
      Lewis rats. In this study, two completely distinct antigenic sites were detected
      within a short form of this peptide. One site is localized in sequence 1182-1191.
      The second site localizes within sequence 1183-1191 and becomes detectable only
      when tryptophan at 1182 is deleted. Lymphocytes sensitized against the first
      determinant recognized a longer peptide as well as whole IRBP. Lymphocytes
      sensitized against the second determinant recognized only two peptides 1184-1191
      and 1183-1191. No cross reactivity was detected between these two determinants.
      Amino acid substitution of tryptophan with alanine or glutamic acid at 1182 in
      peptide 1182-1191 caused complete loss of uveitogenicity and immunogenicity,
      while substitution with phenylalanine did not change any immunological activities
      of the original peptide. The unique immunological properties of IRBP-derived
      peptides were discussed.

PMID- 1377868
TI  - [The natural history of serous retinal pigment epithelial detachment].
AB  - The natural history of 25 eyes of 21 patients with serous retinal pigment
      epithelial detachment (PED) within the vascular arcade was retrospectively
      studied to clarify the risk factors for development of choroidal neovascular
      membranes (NVM) from PED (mean age 55.8 +/- 10.4 years; mean follow-up 18.8 +/-
      10.3 months). During the follow-up period, 6 eyes (24%) developed NVM. The
      significant risk factors for NVM development at the first visit were: older
      patient age (greater than 60 years): larger PED size (greater than 1 disc
      diameter): presence of PED in the fovea. Eyes with sensory retinal detachment
      that did not decrease during the follow-up had a significant high risk for NVM
      development. Eyes with NVM development showed significantly worse visual
      prognosis as compared to those with no NVM development. Life-table analysis
      (Kaplan-Meier method) showed that the incidence of developing NVM was 8% at 3
      months, 16% at 6 months, and 24% at 9 months. These results suggested that the
      size and location of PED and clinical course of sensory retinal detachment in
      addition to the patient age may be important determinants of the prognosis of
      PED.

PMID- 1377869
TI  - Symbols, rationality, and justice: rationing health care.
AB  - Proposals to ration health care in the United States meet a number of objections,
      symbolic and literal. Nonetheless, an acceptance of the idea of rationing is a
      necessary first step toward universal health insurance. It must be understood
      that universal health care requires an acceptance of rationing, and that such an
      acceptance must precede enactment of a program, if it is to be economically sound
      and politically feasible. Commentators have argued that reform of the health care
      system should come before any effort to ration. On the contrary, rationing and
      reform cannot be separated. The former is the key to the latter, just as
      rationing is the key to universal health insurance.

PMID- 1377870
TI  - Molecular cytogenetic and clinical studies of 42 patients with marker
      chromosomes.
AB  - The molecular cytogenetic characterization and clinical details of 20 patients
      with marker chromosomes are presented. These 20 patients, together with another
      22 patients previously published, represent a cohort in which the chromosomal
      origin of the marker chromosomes was successfully determined in all but one case.
      Examination of the pooled data suggests that the satellited markers derived from
      chromosomes 14, 15 (when metacentric or submetacentric), those whose origin is
      either 13 or 21, and those small ring autosomal markers derived from both alphoid
      and satellite II or III pericentric heterochromatin of chromosomes 1, 9, 15, and
      16 are all associated with a low risk of phenotypic abnormality. The markers
      identified as i(18p), ring chromosomes derived from various autosomes, and
      satellited markers derived from chromosome 22 are associated with a high risk of
      phenotypic abnormality. The phenotype of patients with acrocentric markers
      derived from chromosome 15 was equivocal, perhaps as a result of imprinting.
      Additional data are required to confirm these trends. The mild mental retardation
      and abnormal face of a patient with a small ring chromosome derived from
      chromosome 4 are described. Identification of patients with small rings
      originating from particular chromosomes may allow the recognition of new
      syndromes.

PMID- 1377871
TI  - Choroidal neovascularization occurring within a demarcation line.

PMID- 1377872
TI  - Intracellular band 3 immunostaining in type A intercalated cells of rabbit
      kidney.
AB  - Intercalated cells (ICs) in the collecting duct and the connecting tubule (CNT)
      are involved in H+ secretion and HCO3- reabsorption. H+ secretion is mediated by
      an H(+)-adenosinetriphosphatase in the apical plasma membrane, whereas a band 3
      like Cl(-)-HCO3- exchanger in the basolateral membrane is responsible for HCO3-
      reabsorption. Recent studies have reported that a band 3-like protein is also
      present in mitochondria in rabbit ICs. The purpose of this study was to establish
      the subcellular location of the band 3-like Cl(-)-HCO3- exchanger in rabbit ICs
      by electron microscopic immunocytochemistry using a monoclonal antibody, IVF12,
      against erythrocyte band 3 protein. Rabbit kidneys were preserved by in vivo
      perfusion with a paraformaldehyde-lysine-periodate solution and processed for
      immunocytochemistry using a horseradish peroxidase preembedding technique. Band 3
      immunostaining was observed on the basolateral plasma membrane of ICs in the
      outer medullary collecting duct and type A cells in the cortical collecting duct
      (CCD) and CNT. In addition, distinct staining for band 3 was present in numerous
      small vesicles and in multivesicular bodies in type A ICs in the CCD and CNT.
      However, there was no evidence of band 3 immunostaining of mitochondria or of the
      apical plasma membrane in any cells of the collecting duct. These observations
      suggest that basolateral Cl(-)-HCO3- exchangers in type A ICs in the rabbit
      kidney are stored in intracellular vesicles and possibly degraded in the vascular
      lysosomal system when these cells are in a resting state. The previously reported
      band 3 immunolabeling of mitochondria could not be confirmed.

PMID- 1377873
TI  - Insulin-like growth factor I in initial renal hypertrophy in potassium-depleted
      rats.
AB  - We investigated insulin-like growth factor I (IGF-I) in the kidney during the
      initial renal enlargement induced by dietary K depletion in rats. Kidney weight
      increase was significant after 3 days of K depletion and amounted to 29% after 7
      days compared with pair-fed controls [839 +/- 34 vs. 648 +/- 17 mg (SE), P less
      than 0.01]. The kidney growth occurred despite almost complete arrest in body
      weight gain in K-depleted animals (8 +/- 3 vs. 34 +/- 4 g/7 days in controls, P
      less than 0.01). Whole kidney protein, RNA, and DNA estimations indicated that
      cellular hypertrophy during the first 4 days was followed by hyperplasia.
      Immunoassayable kidney IGF-I concentration increased by 106% (673 +/- 30 vs. 327
      +/- 14 ng/g, P less than 0.01) in K-depleted animals 24 h after induction of K
      depletion, stayed elevated until day 4, and returned to control levels on day 7.
      After K depletion for 24 h, IGF-I immunostaining was markedly increased in the
      medullary parts of the collecting ducts from K-depleted animals, whereas kidney
      IGF-I gene expression (IGF-I mRNA) had decreased by 36%. The increase in total
      kidney IGF-I concentration and immunostainable IGF-I in collecting ducts in
      kidneys from K-depleted rats precedes the renal hypertrophy and thereby suggests
      a renotropic role for IGF-I. The increase in kidney IGF-I concentration is not
      associated with increased IGF-I mRNA levels, indicating that non-transcriptional
      mechanisms may be responsible for the renal IGF-I accumulation.

PMID- 1377874
TI  - Nephrotoxic antiserum identifies a beta 1-integrin on rat glomerular epithelial
      cells.
AB  - A postulated mechanism of immune glomerular injury is a direct interaction
      between antibody and glomerular epithelial cell (GEC) surface antigens. To
      explore this hypothesis, we examined the interaction of the noncomplement-fixing
      gamma 2-subclass of sheep anti-rat nephrotoxic serum (NTS), which causes
      immediate complement- and neutrophil-independent proteinuria in vivo, with rat
      GECs in culture. Reactivity of NTS with GEC surface antigens was determined by
      positive immunofluorescence of GEC plasma membranes and by the ability of NTS
      coated tissue culture wells to provide an adhesive substrate for GECs. NTS
      immunoprecipitated two proteins (135 and 118 kDa) from surface-labeled GECs.
      Proteins of similar molecular mass were precipitated by a polyclonal rabbit
      antibody that identifies the beta 1-integrin chain of the mouse fibronectin
      receptor (anti-FnR). In addition, NTS identified similarly sized bands on Western
      blot analysis of cell membranes from isolated rat glomeruli. Similar reactivity
      was eluted from the glomeruli of proteinuric rats injected with NTS. NTS
      significantly inhibited GEC adhesion to laminin, types I and IV collagen, and
      fibronectin and prevented GEC spreading on types I and IV collagen. Anti-FnR
      similarly inhibited GEC adhesion. Cell viability was not affected. These results
      show that NTS recognizes a pair of GEC surface proteins that have the
      characteristics of an alpha- and beta 1-integrin and, at low concentrations,
      disrupt cell-matrix interactions.

PMID- 1377875
TI  - Substance P modulates autonomic nerve activity in canine hearts.
AB  - We examined the hypothesis that substance P (SP) acts as an "afferent
      neuromodulator" in the heart regulating the response of the cardiac autonomic
      nerves to reflexes originating in the heart. We employed the acute, isovolumic
      canine heart preparation in which the amplitude of the chamber pressure
      accurately reflects changes in contractility. The heart was decentralized except
      for one-half of the right vagus, which was left intact to permit afferent
      communication with the central nervous system, while the remaining one-half was
      tightly ligated so that the distal part could be used for efferent stimulation.
      SP was injected in doses of 2-10 micrograms ic. There were no significant
      inotropic responses to 2 and 5 micrograms SP, whereas 10 micrograms produced
      positive inotropy of 5-15%. When vagal tone was elevated with sustained vagal
      stimulation, the same doses of SP increased contractility by 12-28%. Similarly,
      during right stellate ganglion stimulation (SS), SP decreased contractility 8
      22%. After the intact half of the right vagus was sectioned, SP modulation of
      vagal responses was unaffected, while modulation of atrial, but not ventricular,
      responses to SS was significantly attenuated. When tested on a series of cardiac
      denervated dogs, SP had no effect on cardiac inotropy at any dose. However, when
      contractility was increased with isoproterenol infusion, SP caused a small
      decrease in ventricular contractility. These results suggest that SP acts as a
      modulator of cardiac autonomic neural tone. It is possible that the neuropeptide
      is released from intramyocardial afferent collateral fibers and inhibits the
      elevation in vagal or sympathetic nerve activity initiated by activation of
      cardiac primary afferent nerves.

PMID- 1377876
TI  - Cyclosporin inhibits mitochondrial calcium efflux in isolated adult rat
      ventricular cardiomyocytes.
AB  - Exchangeable intracellular Ca2+ as measured by 45Ca2+ uptake more than doubled
      when isolated adult rat ventricular cardiomyocytes were incubated 30 min with 8
      microM cyclosporin; nevertheless the cells retained a normal rod-shaped
      morphology. High concentrations of ouabain caused a similar increase in 45Ca2+
      uptake, but in this case the Ca2+ overload caused nearly all cells to
      hypercontract into a round disorganized form. The response to cyclosporin was
      concentration dependent with an apparent half-maximal effective concentration of
      0.5 microM for enhancement of net 45Ca2+ accumulation. Verapamil (1 microM) could
      not inhibit this cyclosporin effect, but it was abolished by a 5-min
      preincubation with 12 microM crude ruthenium red. Cyclosporin also decreased the
      rate of 45Ca2+ efflux from prelabeled myocytes into Ca(2+)-containing and Ca(2+)
      free media. These data are consistent with inhibition of mitochondrial 45Ca2+
      efflux through the cyclosporin-sensitive mitochondrial inner membrane pore. It
      would appear that periodic transient increases in mitochondrial inner membrane
      permeability provide a pathway for mitochondrial Ca2+ extrusion under relatively
      normal conditions in isolated adult rat heart cells.

PMID- 1377877
TI  - Effect of Ca2+ ionophores on membrane potential of pig coronary artery
      endothelial cells.
AB  - Ca2+ ionophores (A23187 and ionomycin) were used to determine whether an increase
      in cytosolic Ca2+ plays a direct role in pig coronary endothelial cell
      hyperpolarization. Ionophores induced concentration-dependent hyperpolarizations
      that were not altered by the presence of N omega-nitro-L-argnine (L-NNA), and
      inhibitor of nitric oxide synthesis. d-Tubocurarine decreased by 65-89% the
      A23187- and substance P (SP)-generated hyperpolarization of endothelial cells. To
      study the role of endothelial cell hyperpolarization in the endothelium-dependent
      relaxation of precontracted coronary artery strips, A23187 and SP concentration
      response curves were built up in the presence of d-tubocurarine and/or L-NNA. A
      decrease in the maximal response was observed only when both d-tubocurarine and L
      NNA were present. Our direct in situ approach gives results in agreement with a
      gating of Ca(2+)-activated K+ channels during A23187- and SP-induced
      hyperpolarizations of endothelial cells. We suggest that these hyperpolarizations
      play a role in the endothelial cell-dependent relaxation induced by A23187 and SP
      in the pig coronary artery.

PMID- 1377878
TI  - Effects of hypertonic saline and dextran 70 resuscitation on microvascular
      permeability after burn.
AB  - Administration of hyperosmolar fluids to burn patients has been proposed as a
      means of decreasing resuscitative fluid volume and, subsequently, wound edema
      accumulation. To test this hypothesis, canine hindpaw lymph flow (QL) and lymph
      (CL) and plasma (CP) total protein concentrations were measured, and capillary
      filtration coefficient (Kf) was calculated before and for 6 h after a 5-s 100
      degrees C footpaw scald. Scald was followed 30 min later by bolus infusion (4
      ml/kg) of 7% saline or 6% Dextran 70 or the two in combination. Before scald,
      venous pressure was elevated until a minimal CL/CP was reached. The reflection
      coefficient (sigma d) was calculated by the formula: 1-minimal CL/CP. Scald
      increased QL, CL/CP, and Kf, but sigma d was decreased (P less than 0.05).
      Compared with burn alone, 7% saline exacerbated burn-induced increases in QL and
      Kf. In contrast, infusion of Dextran 70 did not exacerbate these changes in QL or
      Kf. Perhaps more importantly, Dextran 70 may have attenuated the increase in
      CL/CP and reduced edema formation in the burned hindpaw. However, the addition of
      7% saline to the dextran eliminated these beneficial effects.

PMID- 1377879
TI  - Cardiomyocyte proliferation in mice expressing alpha-cardiac myosin heavy chain
      SV40 T-antigen transgenes.
AB  - To determine the proliferative potential of adult ventricular cardiomyocytes, we
      have generated transgenic mice that express the SV40 large T-antigen oncogene in
      the heart. A fusion gene comprised of the rat alpha-cardiac myosin heavy chain
      promoter and the SV40 early region was used to target oncogene expression to the
      myocardium. Expression of SV40 large T-antigen was observed in both atrial and
      ventricular cardiomyocytes in adult transgenic animals. T-antigen expression was
      associated with hyperplasia in the targeted cells. Immunohistological analysis
      indicated that the proliferating cells continued to express sarcomeric myosin.
      Electron microscopic examination demonstrated that cardiomyocytes in various
      stages of the cell cycle retained ultrastructural characteristics typical of
      mitotic cardiac muscle cells in vivo. Cardiomyocytes isolated from transgenic
      tumors were able to proliferate in culture and retained a differentiated
      phenotype, as evidenced by spontaneous contractile activity. Preliminary studies
      indicate that these cells can undergo a limited number of passages while
      retaining this differentiated phenotype. These studies demonstrate that both
      ventricular and atrial cardiomyocytes from transgenic mice proliferate in
      response to targeted T-antigen expression.

PMID- 1377880
TI  - Reduction of glutamine synthetase mRNA in hypertrophied skeletal muscle.
AB  - Skeletal muscle glutamine synthetase (GS) expression is reduced by endurance
      exercise and is increased when normal innervation is interrupted. This
      investigation was undertaken to determine whether GS expression is downregulated
      by the increased contractile activity associated with functional overload.
      Plantaris muscles overloaded for 30 days by synergist ablation were 70% heavier
      than those in sham-operated and unoperated control muscles. GS mRNA levels from
      hypertrophied muscles, measured by Northern and dot-blot hybridization, were
      reduced to 30% of controls. Changes in total RNA concentration and the proportion
      of poly(A)+ RNA in the total RNA pool did not account for the decline in GS mRNA.
      Despite reduced levels of GS mRNA, GS enzyme activity (nmol.h-1.mg protein-1) was
      unchanged in the hypertrophied muscles (overload, 79 +/- 5; control, 82 +/- 4).
      To further examine the lack of relationship between GS mRNA and enzyme activity,
      the concentration of glutamine, a known posttranslational modifier of GS
      activity, was measured. Consistent with the observed enzyme activities, muscle
      glutamine was unchanged in hypertrophied muscle (overload, 6.2 +/- 0.3; control,
      5.8 +/- 0.4 mumol/g tissue). These results suggest that translational or
      posttranslational regulation, other than through alterations in glutamine
      concentration. may play a role in maintaining GS enzyme levels in hypertrophied
      muscle. Moreover, the regulation of GS activity in muscle hypertrophy may differ
      from the regulation with endurance training, in which changes in enzyme activity
      parallel changes in mRNA.

PMID- 1377882
TI  - Cortical synaptogenesis in congenitally hydrocephalic HTX-rats using monoclonal
      anti-synaptic vesicle protein antibody.
AB  - We attempted to develop a method for investigating impairment of synaptogenesis
      quantitatively involving measurement of the fluorescence intensity emitted by
      immunohistochemically stained rat brain using a monoclonal antibody (Mab 171B5)
      against a synaptic vesicle protein (SVP-38). We applied this method to
      congenitally hydrocephalic and non-hydrocephalic brains of HTX-rats, and compared
      the postnatal changes in the fluorescence intensity in the molecular layer of the
      cerebral cortex. In non-hydrocephalic HTX-rats, the fluorescence intensity
      remained nearly unchanged from the 1st to 7th postnatal day and then increased at
      an almost linear rate until the 21st postnatal day, when it reached 4.5 times the
      value on the 7th postnatal day. The increase thereafter was gradual until the
      28th postnatal day. In hydrocephalic HTX-rats, the fluorescence intensity
      increased nearly in parallel with that in non-hydrocephalic HTX-rats up to the
      21st postnatal day. On the 28th postnatal day, the fluorescence intensity showed
      a marked reduction (P less than 0.01). This finding indicates that despite the
      presence of continuous pressure due to progressive ventricular dilatation after
      birth, synaptogenesis in the cerebral cortex may be relatively resilient.

PMID- 1377881
TI  - Human antibody responses to epitopes on the Plasmodium falciparum gametocyte
      antigen PFS 48/45 and their relationship to infectivity of gametocyte carriers.
AB  - Antibodies in human sera recognizing epitopes I, IIa, III, and IV on the
      Plasmodium falciparum gametocyte antigen Pfs 48/45 have been investigated by
      competitive enzyme-linked immunosorbent assay. More than one-third of the
      residents of three villages in Madang, Papua New Guinea responded to epitopes I,
      IIa and III, with little variation by village or with time. There was a bimodal
      distribution of positive sera by age, with the highest proportion of responders
      in the 5-9- and greater than 20-year-old age groups. The data suggest a lower
      prevalence of antibodies against epitopes IIa and III in P. falciparum gametocyte
      carriers than in non-carriers. Enhancement of binding of monoclonal antibodies to
      epitopes IIa and III was also observed more frequently with sera from gametocyte
      carriers. Sera from gametocyte carriers in Papua New Guinea and Thailand, whose
      infectivity to mosquitoes had been tested, were used to examine the relationship
      between recognition of particular epitopes and infectivity. There was a
      significant association between lack of infectivity of P. falciparum gametocyte
      carriers and recognition of epitope IIa on Pfs 48/45 by antibodies in their sera.

PMID- 1377883
TI  - A monoclonal antibody (ST-1) directed to the native heparin chain.
AB  - A mouse monoclonal antibody, ST-1, was raised against heparin complexed to
      Salmonella minnesota. Characterization of this antibody showed that it recognizes
      an epitope in the intact molecule of heparin that is present regardless of its
      source or anticoagulant activity. ST-1 is the first monoclonal antibody specific
      for the intact unmodified molecule of heparin to be described. 3H-labeled heparin
      in solution was immunoprecipitated by ST-1, and the formation of the 3H-labeled
      immunocomplex was selectively inhibited by unlabeled heparin. No cross-reactivity
      of ST-1 was observed with other glycosaminoglycans such as heparan sulfate,
      chondroitin sulfate, hyaluronic acid, dermatan sulfate, and keratan sulfate, or
      with polyanionic polymers such as dextran sulfate. Selective removal of the N
      sulfate groups or N,O-desulfation of heparin strongly reduced the binding of ST
      1. Inhibition of binding was also observed after carbodiimide reduction of the
      carboxyl groups of the uronic acid units of heparin. Competitive assays of ST-1
      binding to heparin immobilized on poly-L-lysine-coated plates using
      oligosaccharides of different sizes that arose from HNO2 cleavage of heparin
      showed that the minimum fragment required for reactivity of ST-1 is a
      decasaccharide.

PMID- 1377884
TI  - A novel serum assay for breast epithelial antigen using a fusion protein.
AB  - Serum levels of breast epithelial antigens (BrE-Ags) are presently used in the
      follow-up of breast cancer patients. Available assays do not have optimal
      sensitivity and rely on reagents that could vary in their source and purity. A
      novel competitive solid-phase radioimmunoassay was developed for BrE-Ags that
      consists of the NP5 fusion protein, produced in Escherichia coli, that is
      composed of beta-galactosidase and polypeptide sequence obtained from a breast
      carcinoma cell line cDNA library, and anti-human milk fat globule monoclonal
      antibody Mc5. The fusion protein carries an altered epitope sequence (mimotope)
      that is similar, but not identical, to that found in the native antigen. This new
      competitive assay configuration has two essential features, a solid-phase
      affinity step that purifies the fusion protein carrying the mimotope for Mc5 and
      a competitive step that provides quantitation. Serum values for this assay show
      high specificity and sensitivity for breast cancer patients when compared to
      normal subjects and post-surgical breast cancer patients during their disease
      free period.

PMID- 1377885
TI  - Immunodetection after complete destaining of coomassie blue-stained proteins on
      immobilon-PVDF.
AB  - A technique that simplifies the localization of an immunodetectable protein in
      relation to the other electrophoresed proteins is described. Proteins are
      transblotted onto a polyvinylidene difluoride (PVDF) membrane and visualized by
      staining with Coomassie brilliant blue R-250, and a photograph of the protein
      pattern is taken. The Coomassie blue-stained PVDF membrane is then completely
      destained using a 25% acetic acid/50% methanol solution that allows subsequent
      immunostaining on the same membrane. The technique uses common laboratory
      reagents, is rapid, and has been shown to be applicable for a variety of proteins
      using both monoclonal and polyclonal antibodies and a variety of transblots.

PMID- 1377886
TI  - Using microparticle labeling and counting for attomole-level detection in
      heterogeneous immunoassay.
AB  - A new heterogeneous "sandwich" immunoassay utilizing microparticles as labels to
      realize high sensitivity is described. In this method, antibody fixed on the
      microparticles reacts with antigen previously trapped on a microplate surface,
      which makes the antigen molecules visible and countable with an inverted optical
      microscope. The method is highly sensitive because the reacted single
      microparticle, therefore single antigen molecule, can be detected. The
      sensitivity depends both on the reaction efficiency of the immunoreaction and on
      nonspecific adsorption of the microparticles on the microplate surface.
      Therefore, the protocol for preparing microparticle having antibody on the
      surface and a microplate having capture antibody was investigated to realize high
      sensitivity. Carboxylated microparticles of 0.76 microns in diameter were
      conjugated with affinity-purified antibody using 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide. It was determined that 1 g microparticles had
      880 micrograms antibody (approximately 1100 antibody molecules per 1
      microparticle). The immunoreaction efficiency reached 18% at 1 x 10(-13)
      mol/liter antigen concentration. The lower detection limit was 3.1 x 10(-14)
      mol/liter (1.6 amol) using human alpha-fetoprotein as a model antigen.

PMID- 1377887
TI  - Cetyltrimethylammonium bromide discontinuous gel electrophoresis: Mr-based
      separation of proteins with retention of enzymatic activity.
AB  - A discontinuous polyacrylamide and agarose gel electrophoresis system is
      presented here which allows the fine separation of proteins based on molecular
      weight with the concomitant retention of native enzymatic activity. This system,
      referred to as the CAT gel, uses the cationic detergent cetyltrimethylammonium
      bromide (CTAB) and includes a stacking gel based on the zwitterion arginine and
      the buffer N-tris(hydroxymethyl)-methylglycine. The CAT gel system allows
      specific enzyme histochemical detection and localization of proteins after gel
      electrophoresis. We present evidence that the CAT system stacked and separated a
      broad range of proteins into discrete bands which migrate as a linear function of
      log Mr. We have also assessed the effect of CTAB solubilization on the activity
      of several proteins and showed that some proteins separated by CAT
      electrophoresis maintain high levels of native enzymatic activity and may be
      detected histochemically in situ.

PMID- 1377888
TI  - High-yield recovery of electroblotted proteins and cleavage fragments from a
      cationic polyvinylidene fluoride-based membrane.
AB  - In this report we describe the use of a novel, experimental, polyvinylidene
      fluoride-based membrane with a cationic surface for the isolation by
      electroblotting of small amounts of proteins separated by gel electrophoresis for
      further characterization by protein fragmentation for internal sequence analysis.
      The membrane is characterized by a surface that mediates primarily ionic
      protein/membrane interactions and that allows the recovery of adsorbed proteins
      at high yields under relatively mild conditions. In electroblotting experiments,
      the novel membrane has a binding capacity that is at least equivalent to that of
      standard polyvinylidene fluoride membranes and is compatible with both chemical
      and enzymatic fragmentation of blotted proteins in situ. Intact electroblotted
      proteins, or fragments thereof, were eluted at high yields. Further structural
      analysis is demonstrated using reverse-phase high-performance liquid
      chromatography or gel electrophoresis to separate cleavage fragments for either
      pulsed-liquid- or solid-phase automated sequence analysis.

PMID- 1377890
TI  - Large-scale purification of calf pancreatic zymogen granule membranes.
AB  - A protocol for isolating milligram quantities of highly purified zymogen granule
      membranes from calf pancreas was developed. The method provides a fivefold
      enriched zymogen granule fraction that is virtually free from major isodense
      contaminants, such as mitochondria and erythrocytes. Isolated granules are
      osmotically stable in isosmotic KCl buffers with half-lives between 90 and 120
      min. They display specific ion permeabilities that can be demonstrated using
      ionophore probes to override intrinsic control mechanisms. A Cl- conductance, a
      Cl-/anion exchanger, and a K+ conductance are found in the zymogen granule
      membrane, as previously reported for rat pancreatic, rat parotid zymogen
      granules, and rabbit pepsinogen granules. Lysis of calf pancreatic secretory
      granules in hypotonic buffers and subsequent isolation of pure zymogen granule
      membranes yield about 5-10 mg membrane protein from approximately 1000 ml
      pancreas homogenate. The purified zymogen granule membranes are a putative
      candidate for the rapid identification and purification of epithelial Cl-
      channels and regulatory proteins, since they contain fewer proteins than plasma
      membranes.

PMID- 1377891
TI  - Enzymatic synthesis of p-nitrophenyl 4(5)-O-beta-D-galactosyl-alpha
      maltopentaoside as a substrate for human alpha-amylases.
AB  - Enzymatic modification at the nonreducing end D-glucosyl residue of p-nitrophenyl
      alpha-maltopentaoside was developed by using the transglycosylation of beta-D
      galactosidase from Bacillus circulans. The enzyme regioselectively synthesized p
      nitrophenyl 4(5)-O-beta-D-galactosyl-alpha-maltopentaoside (a yield of 12.0%
      based on the amount of p-nitrophenyl alpha-maltopentaoside added) on a
      preparative scale from lactose as a donor and p-nitrophenyl alpha-maltopentaoside
      as an acceptor. It revealed that the nonreducing end galactosyl group of p
      nitrophenyl 4(5)-O-beta-D-galactosyl-alpha-maltopentaoside did not prohibit the
      action of human salivary and pancreatic alpha-amylases. This derivative was shown
      to be very suitable as a novel substrate for analytical use of human alpha
      amylase assay in serum through a conjugated reaction involving glucoamylase and
      alpha-D-glucosidase.

PMID- 1377889
TI  - Characterization of insulin-like growth factor binding proteins by two
      dimensional polyacrylamide gel electrophoresis and ligand blot analysis.
AB  - Insulin-like growth factor binding proteins (IGFBPs) in pregnant baboon serum and
      tissue culture media obtained following explant culture of uteri from pregnant
      baboons were characterized by two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (2D SDS-PAGE) followed by Western ligand blot
      analysis using 125I-labeled IGF-I. IGFBP-1 (Mr 30,000; pI 4-4.2), IGFBP-2 (Mr
      34,000, pI 5.7-6.2), IGFBP-3 (doublet Mr 42-48,000; pI 6.2-6.8), and IGFBP-4 (Mr
      24,000; pI 5.7-6.0) were clearly separated from one another. The authenticity of
      IGFBP-1, -2, and -3 was verified by immunoprecipitation using polyclonal
      antibodies followed by ligand blotting. Specificity of 125I-labeled IGF-I binding
      to IGFBPs was also determined by competitive binding studies using unlabeled IGF
      I and -II. This technique allows for the identification of IGFBPs in complex
      biological fluids on the basis of their characteristic Mr and pI with or without
      the availability of specific antibodies and can be done rapidly using the mini 2D
      SDS-PAGE systems.

PMID- 1377892
TI  - Critical threshold for tissue viability as determined by laser Doppler flowmetry.
AB  - As a noninvasive method for continuous evaluation of tissue perfusion, laser
      Doppler flowmetry fulfills many of the prerequisites of an ideal objective
      monitor. A critical threshold for insuring flap viability, however, has not been
      universally accepted. In this experimental design using pedicled epigastric flaps
      in rats, it was determined that if flow alterations in an otherwise healthy flap
      always exceeded 30% of the initial baseline value, consistent viability could be
      predicted. Although this relative critical index could be established, the
      variability of even intraspecies flow rates precluded defining any specific
      numerical index of flow that could always predict flap survival.

PMID- 1377893
TI  - C-erbB-2 expression in squamous cell carcinoma of the head and neck.
AB  - Seventy-five squamous cell carcinomas of the head and neck were analysed for c
      erbB-2 expression using immunohistochemical techniques with four different c-erbB
      2 antibodies. No membrane staining was seen in any of the squamous cell
      carcinomas studied with any of the antibodies; however, c-erbB-2 cytoplasmic
      staining was seen in 60 per cent of the tumours. The significance of cytoplasmic
      staining is discussed and that it may possibly represent elevated c-erbB-2
      expression in squamous cell carcinomas. C-erbB-2 cytoplasmic staining was also
      observed in 10 of 23 normal specimens obtained from the resection margin of the
      tumours. No correlations were found between positive c-erbB-2 cytoplasmic
      staining and any of the clinicopathological parameters or survival.

PMID- 1377894
TI  - Human breast carcinoma cell lines: ultrastructural, genotypic, and
      immunocytochemical characterization.
AB  - Two new breast carcinoma cell lines, designated as UISO-BCA-1 and UISO-BCA-2,
      have been established from pleural effusions of postmenopausal women. Both cell
      lines show properties of mammary epithelial cells, such as positive
      immunoreactivity to cytokeratins and human milk fat globulin, presence of
      desmosomal junctions, numerous microvilli, intracytoplasmic duct-like vacuoles
      and tonofilaments. UISO-BCA-1 and UISO-BCA-2 cells differ from each other with
      respect to cellular morphology, ultramicroscopic details, immunoreactivity to Her
      neu oncogene protein, chromosomal mode and in vivo and in vitro growth rates.
      UISO-BCA-1 cells are well-differentiated (as evident from their morphology and
      ultrastructural details) and hyperploid (42-114 chromosomes). In vitro, UISO-BCA
      1 cells are fast growing, with a population doubling time of 31.2 +/- 9.6 hrs (n
      = 4), and are tumorigenic (100%) in athymic nude mice. In contrast, UISO-BCA-2
      cells are poorly differentiated, but are also hyperploid, with 54-64 chromosomes.
      UISO-BCA-2 cells are slow growing in vitro (population doubling time: 56.0 +/-
      5.0 hrs [n = 4]) and have limited tumorigenic potency (20-40%). Both these cell
      lines are estrogen and progesterone receptor (less than 10 fmol/mg protein)
      negative.

PMID- 1377895
TI  - Mucoepidermoid carcinoma of the salivary glands: immunohistochemical distribution
      of intermediate filament proteins, involucrin and secretory proteins.
AB  - Mucoepidermoid carcinomas of the salivary gland comprising low (n = 6),
      intermediate (n = 11) and high grade malignant (n = 11) tumors were evaluated for
      immunohistochemical reactivity of cytokeratin (monoclonal antibody KL1, PKK1,
      K8.12), vimentin, involucrin and secretory proteins (lysozyme, LY; lactoferrin,
      LA; alpha 1-antitrypsin, alpha 1-AT and alpha 1-antichymotrypsin, alpha 1-Ach).
      Keratin expression was usually confined to intense staining in epidermoid tumor
      cells, but was negative in almost all mucous cells. Vimentin was coexpressed with
      keratin only in epidermoid tumor cells. Great heterogeneity of intermediate
      filament proteins was found in intermediate and epidermoid tumor cells.
      Involucrin in epidermoid tumor cells was particularly abundant in well
      keratinized cells but was lacking in intermediate and mucous forming cells. The
      frequency of occurrence of positive staining for LY, LA, alpha 1-AT and alpha 1
      Ach was relatively low in mucoepidermoid carcinoma with positive
      immunohistochemical staining for these secretory proteins in mucous forming tumor
      cells, while varying expression was observed in epidermoid tumor cells.

PMID- 1377896
TI  - Proteinolytic activity against IGF-binding proteins involved in the paracrine
      interactions between prostate adenocarcinoma cells and osteoblasts.
AB  - PA-III rat prostate adenocarcinoma cells are capable of inducing osteoblastic
      reaction after inoculation onto rat skeleton. In this study PA-III cells and
      osteoblast-derived rat osteosarcoma cells (UMR 106 cells) were employed to
      characterize the cellular interactions in the PA-III cell-induced bone tumors, in
      vitro. Insulin-like growth factor-I (IGF-I) and conditioned media (CM) of UMR 106
      cells stimlated tritiated-thymidine incorporation into the DNA of PA-III cells
      growing in serum-free media. This effect was inhibited by monoclonal anti-hIGF-I
      antibody. In addition PA-III cell CM contained proteinolytic activity for the IGF
      binding proteins of UMR 106 cell CM (IGFBP-1 and -2). This proteinase activity
      hydrolyzed also benzyloxycarbonyl-lysine thiobenzyl ester (BLT) and its action on
      IGFBPs and BLT was inhibited by benzamidine and aprotinin. Proteinase activity of
      PA-III cell CM when bound covalently to tritiated-dilsopropylfluoro-phosphate
      (DFP) and then analyzed on SDS-PAGE gel electrophoresis, revealed the presence of
      radioactivity linked with a 35 kDa protein band. This proteinase was eluted in
      the void volume of the G-50 sephadex column and was retained on and eluted from p
      benzamidine affinity column. The 35 kDa proteinase was retained on and was eluted
      from cartridges of the C18 silica by 80% acetonitrile over 0.1% trifuroacetic
      acid. This partially purified material hydrolyzed BLT substrate and IGFBPs of UMR
      106 cell CM and its effect was inhibited by benzamidine and aprotinin. These data
      indicate that PA-III cell CM contains a 35 kDa proteinase capable of digesting
      the IGFBPs and thus increases the bioavailability of osteoblast-derived IGFs.
      This mechanism may participate in the pathophysiology of the PA-III cell-induced
      bone tumor and its subsequent osteoblastic reaction.

PMID- 1377899
TI  - Identification and cloning of Bradyrhizobium japonicum genes expressed strain
      selectively in soil and rhizosphere.
AB  - The growth of Bradyrhizobium japonicum USDA 110 and USDA 438 in soil extract
      supplemented medium led to transcription of a large amount of DNA not expressed
      in basal medium. Strain USDA 438 was more competitive for the nodulation of
      soybean than strain USDA 110. To identify and isolate DNA regions which were
      expressed specifically in strain USDA 438 but not in strain USDA 110 in response
      to soil extract or soybean root exudate, we developed a subtractive RNA
      hybridization procedure. Several cosmid clones which showed strain-specific gene
      expression were isolated from a USDA 438 gene library. Two clones enhanced
      competitive nodulation when mobilized to USDA 110. The method described may be
      useful for identifying genes expressed in response to environmental stimuli or
      genes expressed differently in related microbial strains.

PMID- 1377898
TI  - In vitro toxicological evaluation of ISIS 1082, a phosphorothioate
      oligonucleotide inhibitor of herpes simplex virus.
AB  - ISIS 1082, a phosphorothioate oligonucleotide targeted to a translation
      initiation codon of herpes simplex virus type 1 (HSV-1) and herpes simplex virus
      type 2 (HSV-2) virion capsid protein UL13 inhibits in vitro viral replication. To
      better understand the pharmacological properties of ISIS 1082, we examined its
      effects in nonvirally infected HeLa cells by using a number of cytotoxicity
      assays. Our data indicate that ISIS 1082 had no effect on HeLa cell viability as
      measured by cellular proliferation and clonogenic assays at concentrations as
      high as 100 microM. Additionally, DNA, RNA, and protein synthesis were only
      inhibited by 25% in cells treated with 100 microM ISIS 1082. The effects of ISIS
      1082 on DNA synthesis were compared with those of acyclovir and
      trifluorothymidine, two clinically used antiherpetic agents. Acyclovir displayed
      effects similar to that of ISIS 1082. However, trifluorothymidine, which has been
      reported to be a potential mutagen and teratogen, significantly altered DNA
      replication at concentrations from 1 to 100 microM. Isolated HeLa DNA polymerases
      were inhibited by the compound, with a 50% inhibitory concentration of 2 microM.
      The in vitro antiviral (K. Draper and V. Brown-Driver, submitted for publication;
      K.G. Draper and V. Brown-Driver, Antiviral Res. Suppl. 1:106, 1991) and
      cytotoxicity studies suggest that ISIS 1082 is a selective, nontoxic,
      antiherpetic therapeutic agent.

PMID- 1377900
TI  - Pseudomonas cepacia suppression of sunflower wilt fungus and role of antifungal
      compounds in controlling the disease.
AB  - In a field experiment, Pseudomonas cepacia J82rif and J51rif increased sunflower
      emergence in the presence of the fungus Sclerotinia sclerotiorum. Pyrrolnitrin,
      aminopyrrolnitrin, and monochloroaminopyrrolnitrin were isolated from J82 and
      identified by using thin-layer chromatography, high-performance liquid
      chromatography, and electron impact-mass, UV, and infrared spectroscopy. In
      growth chamber experiments, two antibiosis-negative mutants were not different
      from the parent strain in protecting the seeds from the fungus.

PMID- 1377897
TI  - Antiretroviral therapy: strategies beyond single-agent reverse transcriptase
      inhibition.

PMID- 1377901
TI  - Phylogenetic position of Rhizobium sp. strain Or 191, a symbiont of both Medicago
      sativa and Phaseolus vulgaris, based on partial sequences of the 16S rRNA and
      nifH genes.
AB  - Phenotypic and DNA sequence comparisons are presented for eight Rhizobium
      isolates that were cultured from field-grown alfalfa (Medicago sativa L.) in
      Oregon. These isolates were previously shown to nodulate both alfalfa and common
      bean (Phaseolus vulgaris (L.) Savi.). The objective of the present study was to
      determine their phylogenetic relationships to the normal symbionts of these
      plants, Rhizobium meliloti and Rhizobium leguminosarum biovar phaseoli,
      respectively. Phenotypically, the Oregon isolates more nearly resemble strains
      from P. vulgaris than those from M. sativa. For example, even though nitrogen
      fixation levels were low with both host species, the symbiotic efficiency of a
      representative Rhizobium isolate (Or 191) with common bean was twice that
      observed with alfalfa. Comparative sequencing of a 260-bp segment of the 16S rRNA
      gene (directly sequenced after amplification by the polymerase chain reaction)
      demonstrated that Or 191 is not closely related to the type strain of R. meliloti
      (ATCC 9930), R. leguminosarum (ATCC 10004), or Rhizobium tropici (CIAT 899).
      Instead, sequence comparisons of the 16S gene indicated that Or 191 belongs to a
      distinct and previously unrecognized taxonomic group that includes strains that
      have previously been called R. leguminosarum bv. phaseoli type I. Unlike type I
      strains, however, Or 191 has only a single copy of the nifH gene (type I strains
      have three), and the nucleotide sequence of this gene is substantially different
      from those of other rhizobial and nonrhizobial nifH genes examined thus far.

PMID- 1377903
TI  - Identification of Brucella spp. by using the polymerase chain reaction.
AB  - The application of two synthetic oligonucleotides as probes and as primers in the
      polymerase chain reaction is presented for a specific, sensitive, and quick
      identification of Brucella spp. The specific oligonucleotide sequences were
      chosen on the basis of a 16S rRNA sequence alignment between Brucella abortus and
      Agrobacterium tumefaciens.

PMID- 1377902
TI  - Characterization of a methane-utilizing bacterium from a bacterial consortium
      that rapidly degrades trichloroethylene and chloroform.
AB  - A mixed culture of bacteria grown in a bioreactor with methane as a carbon and
      energy source rapidly oxidized trichloroethylene and chloroform. The most
      abundant organism was a crescent-shaped bacterium that bound the fluorescent
      oligonucleotide signature probes that specifically hybridize to serine pathway
      methylotrophs. The 5S rRNA from this bacterium was found to be 93.5% homologous
      to the Methylosinus trichosporium OB3b 5S RNA sequence. A type II methanotrophic
      bacterium, isolated in pure culture from the bioreactor, synthesized soluble
      methane monooxygenase during growth in a copper-limited medium and was also
      capable of rapid trichloroethylene oxidation. The bacterium contained the gene
      that encodes the soluble methane monooxygenase B component on an AseI restriction
      fragment identical in size to a restriction fragment present in AseI digests of
      DNA from bacteria in the mixed culture. The sequence of the 16S rRNA from the
      pure culture was found to be 92 and 94% homologous to the 16S rRNAs of M.
      trichosporium OB3b and M. sporium, respectively. Both the pure and mixed cultures
      oxidized naphthalene to naphthol, indicating the presence of soluble methane
      monooxygenase. The mixed culture also synthesized soluble methane monooxygenase,
      as evidenced by the presence of proteins that cross-reacted with antibodies
      prepared against purified soluble methane monooxygenase components from M.
      trichosporium OB3b on Western blots (immunoblots). It was concluded that a type
      II methanotrophic bacterium phylogenetically related to Methylosinus species
      synthesizes soluble methane monooxygenase and is responsible for
      trichloroethylene oxidation in the bioreactor.

PMID- 1377904
TI  - The stimuli releasing histamine from murine bone marrow-derived mast cells
      (BMMC). 3. Effect of coculture with 3T3 fibroblasts on the histamine
      releasability of BMMC.
AB  - Murine bone marrow-derived mast cells at 3 wk in culture were further cultured in
      the absence (N-BMMC) or presence (F-BMMC) of 3T3 fibroblasts in the medium
      containing LI-3, and were examined for their functional responses to either
      histamine releasing stimuli such as compound 48/80 or an inhibitor of histamine
      release, disodium cromoglycate. After 3 weeks in coculture with 3T3 fibroblasts,
      the mast cells increased their histamine content greater than 10 fold, and
      greater than 10% of the cells changed histochemically to become safranin
      positive. F-BMMC released approximately 10% histamine when challenged with
      compound 48/80 or substance P, whereas N-BMMC failed to do so. Furthermore, when
      the sensitized cells were challenged with DNP-HSA antigen, histamine release from
      F-BMMC but not from N-BMMC was inhibited by preincubation with disodium
      cromoglycate. We also examined changes in intracellular Ca2+ ([Ca2+]i) in the
      cells when challenged with compound 48/80. A transient increase in [Ca2+]i was
      observed on stimulation with the compound in F-BMMC but not in N-BMMC. Taken
      together, our results indicate that the interleukin 3-dependent cultured murine
      mast cells change functionally, as well as histochemically, into in vitro
      counterparts of connective tissue mast cells when cocultured with 3T3 fibroblasts
      and may be useful tools for analyzing the mechanisms involved in degranulation
      from connective tissue-type mast cells.

PMID- 1377905
TI  - [Inhibitory effect of inhaled FK-506 on increased bronchial responsiveness and
      eosinophil infiltration in the airway mucosa].
AB  - We examined the effects of inhaled FK-506, a potent immunosuppressive agent, on
      increased bronchial responsiveness to acetylcholine and on eosinophil
      infiltration in a guinea pig models of asthma. The guinea pigs were sensitized by
      repeated inhalation of ovalbumin (OA). Twenty four hours after antigen challenge,
      bronchial responsiveness to acetylcholine significantly increased and a marked
      accumulation of eosinophils in the airways was observed. However, when the guinea
      pigs were treated with aerosolized FK (10 mg/ml) for 5 min per day for 6
      successive days before antigen challenge, the increase in bronchial
      responsiveness was significantly suppressed and the eosinophil accumulation was
      strikingly reduced. Since inhaled FK significantly suppressed these responses,
      there is a possibility that inhaled FK may be a useful therapy for patients with
      chronic bronchial asthma in the future.

PMID- 1377906
TI  - Stimulation of rat parotid secretion by cAMP analogues that synergistically
      activate the type II isoenzyme of the cAMP-dependent protein kinase.
AB  - Beta-adrenergic-stimulated parotid secretion is believed to be mediated by
      activation of the cAMP-dependent protein kinase (PK-A). However, the relative
      roles of the type I and II PK-A isoenzymes are still unclear. Combinations of
      site-selective, lipophilic cAMP analogues that synergistically activate each PK-A
      were used to investigate this problem. The selectivity of synergistic activation
      with these combinations was verified with the partially purified parotid PK-A
      isoenzymes, using kemptide as a substrate. Synergism in activation of PK-AII was
      only seen with 8-thiomethyl cAMP (8-TM) and N-6-benzoyl cyclic AMP (N6B), while
      PK-AI was only synergistically activated by 8-(6-aminohexyl) amino cyclic AMP
      (AHA) and N6B. Additive activation of each isoenzyme was observed for the
      combination of 8-TM and AHA. Rates of amylase secretion from dispersed parotid
      acini in response to secretagogues were determined with a coupled enzyme assay
      for amylase activity, which was adapted for use in a microplate reader. Cells
      were stimulated to secrete during 30 min with different doses (0.1-1.0 mM) and
      combinations of the cyclic nucleotide analogues. Alone, N6B was most effective in
      stimulating amylase secretion. The basal amylase secretory rate was stimulated by
      these secretagogues (0.44 mM) to the following extent: 53-fold (N6B), 8-fold (8
      AHA), 2-fold (8-TM). In combination at a series of concentrations, only 8-TM +
      N6B produced synergistic stimulation of secretion, while AHA + N6B and 8-TM + AHA
      did not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377907
TI  - Limited accumulation of cyclic AMP underlies a modest vasoactive-intestinal
      peptide-mediated increase in cytosolic [Ca2+] transients in GH3 pituitary cells.
AB  - The 4-chlorophenylthio analogue of cyclic AMP evoked profound and long-lasting
      changes in cytosolic [Ca2+] ([Ca2+]i) in pituitary-derived GH3 cells. However,
      vasoactive intestinal peptide (VIP), a hormone considered to act via cyclic AMP,
      was ineffective in modulating [Ca2+]i. The ability of VIP to modulate [Ca2+]i was
      enhanced by treatments that increased intracellular cyclic AMP. Much greater
      concentrations of intracellular cyclic nucleotides were achieved by the analogue
      than with VIP, under any condition. Thus cyclic AMP may play a prominent role in
      regulating [Ca2+]i in these cells, but the ability of hormones to stimulate its
      synthesis is limited, leading to a weak action on [Ca2+]i.

PMID- 1377908
TI  - Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, inhibits induction
      of acute-phase proteins by interleukin-6 alone or in combination with interleukin
      1 in human hepatoma cell lines.
AB  - Okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A,
      inhibited in a dose-dependent manner (5-20 nM) the induction of C-reactive
      protein (CRP), serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus
      interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells. Induction
      of alpha 1-proteinase inhibitor (alpha 1-PI) by IL-6 plus IL-1 or IL-6 alone was
      not significantly affected by OA up to concentrations of 20 nM, above which
      concentration OA was toxic in Hep 3B cells. OA also inhibited the induction of
      CRP, fibrinogen and alpha 1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a
      higher concentration (80 nM). These results suggest that the signal transduction
      mechanisms regulating induction of acute-phase proteins by IL-6, either alone or
      in combination with IL-1, are mediated by activation of protein phosphatases 1
      and/or 2A.

PMID- 1377909
TI  - Growth hormone activates mitogen-activated protein kinase and S6 kinase and
      promotes intracellular tyrosine phosphorylation in 3T3-F442A preadipocytes.
AB  - Physiological concentrations of growth hormone induced a rapid and transient
      activation of mitogen-activated protein kinase (MAP kinase) and S6 kinase in 3T3
      F442A preadipocytes. These effects were abrogated by staurosporine and in cells
      chronically pretreated with phorbol esters, suggesting that protein kinase C is
      involved in the mechanism of activation. In addition, three cytosolic proteins
      exhibited a growth-hormone-dependent increase in tyrosine phosphorylation.

PMID- 1377910
TI  - Glycogenolytic effect of pancreastatin in isolated rat hepatocytes is mediated by
      a cyclic-AMP-independent Ca(2+)-dependent mechanism.
AB  - We have studied the effect of pig pancreastatin on glucose and lactate production
      in freshly isolated rat hepatocytes. Pancreastatin stimulated the rate of glucose
      output, whereas, in contrast with glucagon, it failed to modify the rate of
      lactate production. The effective concentration of pancreastatin was in the range
      0.1-100 nM, with half-maximal rate close to 1 nM. The ability of pancreastatin to
      increase glucose output was abolished by chelation of the calcium in the medium.
      By itself, pancreastatin did not increase cyclic AMP (cAMP) levels and had no
      influence on cAMP levels in glucagon-stimulated hepatocytes. Our results point
      out a possible role of pancreastatin in glycogenolysis. This appears to be
      mediated by a cAMP-independent Ca(2+)-dependent mechanism.

PMID- 1377911
TI  - Epitope mapping by cDNA expression of a monoclonal antibody which inhibits the
      binding of von Willebrand factor to platelet glycoprotein IIb/IIIa.
AB  - In order to study the structure-function relationship of von Willebrand Factor
      (vWF), we have located the epitope of a well-characterized monoclonal antibody
      (MAb) to vWF (MAb 9). This MAb reacts with the C-terminal portion of the vWF
      subunit, SPII fragment [amino acids (aa) 1366-2050], which includes an Arg-Gly
      Asp (RGD) sequence at positions 1744-1746, and totally inhibits vWF and SPII
      binding to platelet membrane glycoprotein IIb/IIIa (GPIIb/IIIa). A recombinant
      DNA library was constructed by cloning small (250-500 nucleotides) vWF cDNA
      fragments into the lambda gt11 vector and these inserts were expressed as fusion
      proteins with beta-galactosidase. Immunological screening of the library with
      125I-MAb 9 identified three immunoreactive clones. vWF inserts were amplified by
      the PCR and their sequences demonstrated overlapping nucleotides from positions
      7630 to 7855 of vWF cDNA, coding for aa residues 1698-1773 of the mature subunit,
      indicating that this is the epitope of MAb 9. vWF-beta-galactosidase fusion
      protein reacted with 125I-MAb 9 by Western blotting. In a solid-phase
      radioimmunoassay, the purified fusion proteins decreased the binding of vWF to
      125I-MAb 9 by 50%, and this inhibition was dose-dependent between 3.5 and 120 nM.
      Therefore the epitope of MAb 9 is located within aa 1698-1773 of the vWF subunit,
      which includes the RGD sequence implicated in the binding of adhesive proteins of
      GPIIb/IIIa.

PMID- 1377912
TI  - Expression of phosphoenolpyruvate carboxykinase (PEPCK) chimeras in renal
      epithelial cells. Retention of appropriate physiological responsiveness using
      enhancerless retroviral vectors.
AB  - We used an enhancerless U3 mutant retroviral vector to deliver chimeras of the
      phosphoenolpyruvate carboxykinase (PEPCK) promoter region to a renal epithelial
      cell line capable of expressing PEPCK mRNA. Chimeras consisting of the PEPCK
      promoter and chloramphenicol acetyltransferase, neomycin phosphotransferase or
      human growth hormone genes were expressed after viral infection of the NRK52E
      renal epithelial cell line. Virus-delivered sequences in which the direction of
      PEPCK promoter transcription was antegrade to the normal direction of the long
      terminal repeat (LTR)-initiated transcription correctly upon stimulation with
      dexamethasone or 8-bromo cyclic AMP and upon lowering of the extracellular pH.
      Fluorescent primer extension in situ using primers specific for virus-delivered
      sequences of antegrade constructs indicated that a large fraction of NRK52E cells
      could be infected by co-cultivation with virus-producing psi-2 cells without G418
      selection. Virus-delivered constructs whose orientation was opposite to that of
      the LTRs were expressed at very low levels, with transcripts detectable by PCR
      only in RNA from cyclic AMP-treated cells. Using reverse transcription/PCR, we
      demonstrated that the chimeric transcripts were from the internal PEPCK promoter
      rather than a functional or reconstituted Moloney LTR. PEPCK-reporter chimeras
      delivered by retroviral vectors demonstrated a level of expression more
      consistent with the level of expression of the native PEPCK gene than did
      transfected chimeras. This expression system should prove useful for studies of
      the physiological modulation of gene expression in renal tissues.

PMID- 1377913
TI  - cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and
      characterization of the human recombinant enzyme.
AB  - Inositol monophosphatase (EC 3.1.3.25) is a key enzyme in the phosphoinositide
      cell-signalling system. Its role is to provide inositol required for the
      resynthesis of phosphatidylinositol and polyphosphoinositides. It is the probable
      pharmacological target for lithium action in brain. Using probes derived from the
      bovine inositol monophosphatase cDNA we have isolated cDNA clones encoding the
      human and rat brain enzymes. The enzyme is highly conserved in all three species
      (79% identical). The coding region of the human cDNA was inserted into a
      bacterial expression vector. The expressed recombinant enzyme was purified and
      its biochemical properties examined. The human enzyme is very similar to the
      bovine enzyme.

PMID- 1377914
TI  - Epitope mapping reveals conserved regions of an auxin-binding protein.
AB  - There is now good evidence that maize (Zea mays) auxin-binding protein (ABP)
      functions as a receptor. We have synthesized sequential overlapping hexapeptides
      to map the epitopes recognized by a number of antisera to ABP. Only a few regions
      of the protein are recognized, and these are shown to be exposed on the surface.
      Three epitopes predominate, and these are clustered around, but do not include,
      the glycosylation site. A comparison is made between these maps of sera against
      purified ABP, maps of sera raised against recombinant maize ABP expressed in
      Escherichia coli and computer antigenicity predictions. Our anti-(maize ABP)
      serum recognizes ABP counterparts in other plant species. We have used
      immunoblotting to affinity-purify the immunoglobulins which cross-react from the
      antiserum. Epitope mapping of these immunoglobulins suggests that two of the
      three predominant epitopes may be conserved in both monocotyledonous and
      dicotyledonous plants. The possible functional significance of these conserved
      epitopes is discussed.

PMID- 1377916
TI  - Interaction of bleomycin with a bent DNA fragment.
AB  - The interaction of bleomycin with a kinetoplast DNA fragment has been examined
      using various footprinting techniques. This DNA adopts a bent structure and
      displays an unusually low gel mobility on account of its phased runs of adenines.
      The bleomycin-cobalt complex increases the mobility of this DNA fragment, in
      contrast with other DNAs which show a decreased rate of gel migration, suggesting
      that the antibiotic removes DNA bending, possibly via an unwinding mechanism.
      Removal of the bending is confirmed by hydroxy-radical footprinting which
      produces a more even ladder of bands in the presence of the ligand. Cleavage by
      bleomycin is at the sequence G-pyrimidine, though not all such sites are affected
      to the same extent and some cutting is found at GA and GG. DNase I footprinting
      confirms the antibiotic-binding sites but reveals that some strong cleavage sites
      do not yield footprints. Bleomycin renders adenines on the 3' side of its
      cleavage sites (GT, GC and GA) hyper-reactive to diethyl pyrocarbonate.

PMID- 1377915
TI  - Cloning and expression of the thyrotropin-releasing hormone receptor from GH3 rat
      anterior pituitary cells.
AB  - Functional thyrotropin-releasing hormone (TRH) receptors have been expressed in
      Xenopus laevis oocytes following the microinjection of total and poly(A)+ RNA
      from GH3 rat anterior pituitary tumour cells. Under voltage-clamp conditions,
      application of the peptide induced a biphasic Ca(2+)-dependent chloride current.
      The amplitude of the initial, fast, component of the response was dependent on
      the concentration of the hormone and on the amount of mRNA injected. Size
      fractionation of poly(A)+ RNA on a continuous sucrose gradient and Northern blot
      analysis indicated that the receptor was encoded by an mRNA of approx. 3.5 kb. A
      3.28 kbp cDNA encoding the TRH receptor has been cloned and sequenced. Full
      functionality of the predicted 412-amino-acid receptor protein was demonstrated
      by functional expression of cell surface receptors in Xenopus oocytes after both
      cytoplasmic injection of sense RNA transcribed in vitro from this cDNA and
      nuclear injection of the cDNA under the control of the Herpes simplex virus
      thymidine kinase promoter. The predicted protein contains seven putative membrane
      spanning domains and shows significant sequence identify with some G-protein
      coupled receptors. RNA blot analysis indicates that the mRNA for the TRH receptor
      is exclusively expressed in the pituitary gland. Expression studies performed
      with clones in which the 3' region of the mRNA has been successively shortened
      indicate that the 3' terminal region is not an important determinant for
      efficient functional expression in oocytes.

PMID- 1377917
TI  - Peptide-containing nerves in labial salivary glands in Sjogren's syndrome.
AB  - OBJECTIVE: The presence and spatial distribution of peptide-containing nerves in
      labial salivary glands from 10 Sjogren's syndrome patients were compared with
      those in salivary glands from 7 healthy controls. METHODS: Immunoperoxidase
      staining was used to demonstrate vasoactive intestinal peptide (VIP)
      immunoreactive (IR) fibers, postganglionic sympathetic fibers containing the C
      flanking peptide of neuropeptide Y (CPON), and sensory fibers containing
      calcitonin gene-related peptide (CGRP) and substance P. RESULTS: Acini,
      intralobular ducts, small arteries, and postcapillary veins were richly
      innervated by VIP-IR fibers, whereas CPON-, CGRP-, and substance P-IR fibers were
      restricted to blood vessels. Peptide-containing nerves were found surrounding,
      but not in the middle of, the highly inflamed mononuclear cell areas. CONCLUSION:
      This topologic distribution suggests involvement of VIP-IR fibers in vascular,
      motor, and secretory components of the reflex salivary secretion, whereas the
      distribution and the vasoactive actions of CPON, CGRP, and substance P suggest a
      role in the regulation of the salivary gland circulation, and thus of
      transcapillary flow. Excessive release may contribute to a neurogenic
      inflammation. Local depletion and absence of trophic neuropeptide stimuli may
      contribute to acinar atrophy.

PMID- 1377918
TI  - Treatment of lupus nephritis with CD5 PLUS, an immunoconjugate of an anti-CD5
      monoclonal antibody and ricin A chain.

PMID- 1377919
TI  - Producing videotapes as professional marketing tools.
AB  - Professional quality videotapes are an effective way to reach audiences.
      Developing such tapes takes careful planning, time, and money, but they are well
      worth the effort involved. Our new role as "marketing agent" must be played with
      professionalism, expertise, persistence, and a sense of humor.

PMID- 1377920
TI  - Endothelial cell interactions with granulocytes: tethering and signaling
      molecules.
AB  - The adhesion of granulocytes to endothelial cells requires regulated expression
      of molecules on both the endothelial cell and the granulocyte. These pro-adhesive
      molecules have diverse structures and mechanisms of expression, and act either to
      tether the two cells together or as signals that induce activation-dependent
      adhesion events. Combinations of tethering and signaling molecules regulate
      endothelial-cell-granulocyte interactions at the endothelial surface.

PMID- 1377921
TI  - Distribution of DNA cleavages induced by bleomycin and neocarzinostatin in a
      defined sequence of rat glioma cells.
AB  - We have demonstrated the usefulness of a highly reiterated sequence of rat DNA as
      a probe sequence for evaluating the effect of bleomycin (BLM) and
      neocarzinostatin (NCS) at the level of individual nucleotides. The 370 base pairs
      (bp) DNA fragment, purified from rat glioma C6 cells after Hind III digestion,
      was labeled with 32P at either the 3'- or the 5'-ends and then divided into 167
      bp and 203 bp by Hae III. These end-labeled DNA fragments were reacted in vitro
      with BLM or NCS, and electrophoresed on the denaturating 8% polyacrylamide gels
      according to Maxam and Gilbert's sequencing protocol. BLM created DNA strand
      breaks at the guanine-cytosine and guanine-thymine (5'----3') sequences, and NCS
      cleaved DNA at the position of thymines and adenines. The highly reiterated
      sequence of rat brain tumor DNA therefore provides adequate knowledge of DNA
      damages induced by BLM and NCS.

PMID- 1377922
TI  - Effects of vasoactive neuropeptides on human saphenous vein.
AB  - OBJECTIVE: To assess the role of neuropeptides in the control of vascular tone in
      the human saphenous vein the actions of substance P, vasoactive intestinal
      peptide, calcitonin gene related peptide, neuropeptide Y, and somatostatin on
      this blood vessel were examined. METHODS: In vitro organ bath techniques were
      used with preparations of saphenous veins obtained from 29 patients (aged 41-66)
      who were undergoing coronary bypass surgery. RESULTS: Substance P, vasoactive
      intestinal peptide, and calcitonin gene related peptide relaxed pre-constricted
      vessels in a dose dependent manner with a rapid onset of action, taking one to
      two minutes to reach a plateau at each dose. Substance P (10(-9) to 10(-6) mol/l)
      induced relaxation with a maximum response (mean (SEM)) 23.0 (6.6)% of the total
      relaxation induced by glyceryl trinitrate 1 microgram/ml and a 50% maximal
      effective concentration of 6.8 x 10(-9) mol/l. Vasoactive intestinal peptide (10(
      10) to 10(-7) mol/l) produced a relaxation of 27.0 (5.1)% at 10(-7) mol/l. The
      maximum responses induced by substance P and vasoactive intestinal peptide were
      significantly reduced, to 3.7 (2.8)% and 4.7 (2.0)% respectively, after removal
      of the endothelium. Calcitonin gene related peptide (10(-10) to 10(-7) mol/l)
      elicited only 14.3 (2.6)% relaxation at 10(-7) mol/l, and this was not affected
      by removal of the endothelium. By contrast, neuropeptide Y and somatostatin
      exerted concentration dependent constriction on resting vessels. Neuropeptide Y
      (10(-10) to 10(-7) mol/l) caused prolonged contraction (roughly 20 minutes to
      reach a maximum plateau at each dose). At 10(-7) mol/l, the constriction amounted
      to 28.0 (12.0)% of the response to 90 mM KCl, in ring segments with or without
      endothelium. Somatostatin (10(-10) to 10(-6) mol/l) quickly caused contraction
      with a maximum response of 42.7 (15.0)% and a maximum response of 42.7 (15.0)%
      and a 50% maximal effective concentration of 6.7 x 10(-6) mol/l. The constriction
      was greatly increased when endothelium was removed, with a maximum response of
      78.2 (16.8)% and a 50% maximal effective concentration of 4.3 x 10(-7) mol/l.
      CONCLUSIONS: Vasoactive peptides have diverse effects on the vascular tone these
      effects are endothelium dependent. The exact physiological role and implication
      for performance of bypass grafts require further investigation.

PMID- 1377923
TI  - Cardiac rupture after thrombolytic therapy: the use of aprotinin to reduce blood
      loss after surgical repair.
AB  - Emergency cardiac surgery after recent thrombolytic therapy is associated with
      increased blood loss. A patient underwent emergency repair of a ruptured left
      ventricle after intravenous streptokinase treatment for acute coronary occlusion.
      High dose aprotinin was given during the operation to reduce the expected blood
      loss. Surgical repair was successful without bleeding complications. Total
      postoperative blood loss was 365 ml.

PMID- 1377924
TI  - Molecular design of oligomeric channel proteins.

PMID- 1377925
TI  - RNA trans-splicing.

PMID- 1377926
TI  - A comparative study on immunosuppressive effects of cyclosporin A and FK 506 on
      peripheral blood lymphocytes in dogs.
AB  - Immunosuppressive effects of cyclosporin A (CsA) and FK 506 (FK) on peripheral
      blood lymphocytes were studied in dogs in respect to mixed lymphocyte reaction,
      proliferative responses to recombinant interleukin-2 (rIL-2), phytohemagglutinin
      (PHA) and concanavalin-A (Con-A); phenotypes of OKIa1, CD3, CD8 and surface IgM;
      cytotoxic activity against xenogeneic tumor cells. CsA (2.0 or 5.0 mg/kg,
      intravenously) or FK (0.16 mg/kg, intramuscularly) was given to mongrel dogs
      every morning for serial 21 days. The blood concentrations of CsA, measured as
      trough levels by fluorescence polarization method, ranged from 37 to 350 ng/ml in
      dogs administered at 2.0 mg/kg and from 170 to 894 ng/ml in dogs administered at
      5.0 mg/kg during treatment, respectively. In dogs treated with FK at a dose of
      0.16 mg/kg, the drug concentrations in the plasma during treatment ranged from
      0.16 to 1.8 ng/ml. Mixed lymphocyte reaction and proliferative responses to rIL
      2, PHA and Con-A, which were declined by CsA, were not affected by FK. In
      contrast, the proportion of OKIa1+ cells was not affected by CsA, whereas FK
      decreased the proportion of OKIa1+ cells progressively during the course of
      treatment. Cytotoxic activity was suppressed by both CsA and FK. These results
      possibly indicate that CsA and FK exert their immunosuppressive effects via
      different mechanisms.

PMID- 1377927
TI  - Levels of human serum granulocyte colony-stimulating factor and granulocyte
      macrophage colony-stimulating factor under pathological conditions.
AB  - Levels of serum granulocyte colony-stimulating factor (G-CSF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF) in patients with various leukocyte
      disorders were estimated by enzyme-linked immunosorbent assay (ELISA). Some cases
      of acute myelogenous leukemia and aplastic anemia showed elevated serum levels of
      G-CSF and/or GM-CSF, whereas almost all of 23 healthy controls showed G-CSF and
      GM-CSF levels lower than 100 pg/ml. High levels of both types of CSF were noted
      in patients with granulocytosis due to infection. These levels became lower after
      resolution of the infection. Daily changes in serum CSF levels were also examined
      in a patient with autoimmune neutropenia, and it was found that the peripheral
      neutrophilic granulocyte count changed almost in parallel with the serum G-CSF
      level but not with GM-CSF, following the pattern with a delay of about 4-5 h,
      suggesting the possibility that G-CSF mainly regulates peripheral neutrophil
      circulation.

PMID- 1377928
TI  - Comparative effects of a recombinant and a mutein type of granulocyte colony
      stimulating factor on the growth of Meth-A fibrosarcoma with 5-fluorouracil
      chemotherapy.
AB  - The present study was designed to evaluate the effects of a recombinant human G
      CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice
      treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes
      (white blood cell, WBC) reached the peak 12 hours after a single injection of
      either type of G-CSF and decreased to the normal level after 24 hours. Daily
      administration induced a continuous increase in the WBC count, however,
      administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously
      inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5
      FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and
      an insignificant inhibition of tumor growth. The conjunctive administration of G
      CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth,
      and leukopenia was not seen. This augmenting effect was more prominent with KW
      2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in
      restoring the number of leucocytes from leucopenic state and in augmenting the
      tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the
      natural type rhG-CSF.

PMID- 1377929
TI  - Antigen-specific, MHC-unrestricted T cells.
AB  - The published record suggests that in the majority of cases the antigen is
      recognized by the T cell receptor (TCR) as a complex of a foreign antigen and
      amino acid residues contributed by the major histocompatibility complex (MHC)
      antigens, and the antigen-specific, MHC-restricted effector function is an
      unambiguous result of this process. Alternatively, the T cell receptor may
      recognize a particular conformational form of the antigen which is dictated by
      the allelic differences in the MHC, resulting also in MHC-restricted recognition.
      When, however, a T cell which phenotypically fulfills all the requirements
      necessary to perform antigen specific, MHC-restricted function, shows a lack of
      MHC restriction, there are two possible explanations: 1) In addition to the MHC
      restricted, antigen-specific T cell receptor the cell expresses, or has newly
      acquired the expression of another, MHC-unrestricted (NK-like) receptor, or 2)
      The specific antigen recognized by the T cell receptor, is able to bind to the
      receptor and activate the T cell without being presented by the MHC molecule.
      While the first possibility has been extensively described in the literature as
      well as other articles in this issue, the second possibility has not been dealt
      with to the same extent and is the primary focus of this review.

PMID- 1377931
TI  - Combined external beam and intracavitary radiotherapy in oesophageal carcinoma.
AB  - Seventy patients (40 males, 30 female; age 36-87 years, median 72 years) who were
      unsuitable for surgery were referred to the Regional Radiotherapy Centre,
      Newcastle General Hospital with oesophageal carcinoma (54 squamous cell; tumour
      length 2-14 cm). Sixty-seven patients received combined external beam
      radiotherapy (20-50 Gy in 5-20 fractions over 1-4 weeks) followed by
      intracavitary radiation (66 patients received 10 Gy at 1 cm; the remaining 4
      received less) using an endoscopically inserted afterloading technique at 6.4
      Gy/hour. Swallowing was restored in 65 patients (92%), although 39 patients
      (55.7%) subsequently required dilatation. Four developed fistulae (1 day, 2
      months, 11 months, 17 months post-treatment). The actuarial survival was 71% at 6
      months and 42% at 1 year. The combined treatment is well tolerated, with few
      complications and provides good palliation.

PMID- 1377930
TI  - Characterization of the dengue virus-induced helper cytokine.
AB  - Dengue type 2 virus (DV) induces a subpopulation of T lymphocytes of mouse spleen
      to secrete a soluble helper cytokine (HF) which enhances the DV-specific IgM
      antibody plaque forming cells (PFC). The present study undertaken to purify and
      characterize HF shows that it can be purified by low pressure liquid
      chromatography (LPLC) using Sephacryl S-200 column. HF consisted of two subunits,
      having a M(r) of 65-68 kDa on SDS-PAGE, and both had similar activity. The
      isoelectric point of HF was 6.5. HF-specific antisera (HFAS) raised in mice
      neutralized the activity of HF in mice, reacted with it in a Western blot assay,
      and bound HF in an immunosorbent column. HF bound to DV-antigen in an
      immunosorbent column and enhanced only the DV-specific PFC. HF had no effect on
      PFC against heterologous antigens such as Japanese encephalitis virus, Coxsackie
      B4 virus or sheep red blood cells. HF generated in mice of H-2k haplotype,
      enhanced DV-specific PFC in the same strain of mice but had no effect on that in
      the H-2d or H-2q haplotype strains of mice. Thus, DV-induced HF with a M(r) of 65
      68 kDa, antigen-specificity and genetic-restriction differs from most of the
      similarly acting cytokines but appears similar to the cell-free form of T cell
      receptor alpha beta dimer.

PMID- 1377932
TI  - The value of internal fixation and radiotherapy in the management of upper and
      lower limb bone metastases.
AB  - Fifty-four consecutive patients underwent 61 orthopaedic operations for
      metastatic bone disease affecting the upper and lower limbs. These patients were
      subsequently managed using a consistent postoperative radiotherapy (RT) policy.
      There were 27 prophylactic internal fixations and 34 internal fixations of
      pathological fractures. There was a marked difference in survival between these
      groups. The median postoperative survival of the prophylactic (P) group was 15
      months whereas that of the fracture (F) group was 2 months (P less than 0.0001).
      Ninety-three per cent of the P group and 59% of the F group were able to be
      discharged home following treatment. Subsequent local fracture requiring further
      surgical intervention occurred in 11% of the P group and in none of the F group.
      Seventy-eight per cent of the P group and 62% of the F group did not suffer any
      further sequelae at the operation site until the time of death or last follow-up.
      Patient mobility following surgery and RT for metastatic lesions occurring in the
      lower limb was significantly improved in both the P group (P less than 0.05) and
      in the F group (P less than 0.0001) such that 91% and 58%, respectively, of these
      patients were subsequently able to walk.

PMID- 1377933
TI  - Frequent clonal abnormalities of chromosome band 13q14 in B-cell chronic
      lymphocytic leukemia: multiple clones, subclones, and nonclonal alterations in 82
      midwestern patients.
AB  - We performed cytogenetic analyses of peripheral blood lymphocytes from 82
      Midwestern B-cell chronic lymphocytic leukemia (B-CLL) patients. The cells were
      cultured with mitogens for 3-4 days. At least 15 metaphase cells were analyzed in
      79 (96%) cases. Fifty (63%) of the 79 patients had clonal chromosomal
      alterations. Structural modifications of the long arm of chromosome 13 at or near
      band 13q14 were the most frequent abnormalities, identified in 23 (46%) of the
      patients with clonal abnormalities. In several patients, the abnormality
      involving band 13q14 was the sole chromosomal alteration. There was a high
      incidence of complex karyotypes. Nine patients had multiple subclones that
      appeared to result from clonal evolution; seven patients had cytogenetically
      unrelated clones; three patients had both subclones and cytogenetically unrelated
      clones. Nonclonal abnormalities were also prominent. Our study confirms the high
      incidence of clonal abnormalities involving chromosome arm 13q and documents the
      clustering of abnormalities at band 13q14 in B-CLL. The evidence for clonal
      evolution and the presence of multiple unrelated clones in these patients suggest
      that B-CLL may not be a karyotypically stable disease.

PMID- 1377934
TI  - Karyotypic evolution of a murine mammary adenocarcinoma in vitro and during
      progression from primary to metastatic growth in vivo.
AB  - We have previously described a murine mammary tumor cell line (SP1) that
      metastasizes when transplanted into the mammary gland, but not when injected into
      the subcutaneous site. We used cytogenetic markers to assess genetic
      heterogeneity, and to monitor the selection and evolution of karyotypically
      distinct cell types during primary tumor growth and in metastases. The SP1 tumor
      cells are hypotetraploid (mean chromosome number = 72), and have at least four
      karyotypically distinct cell types. We found no consistent pattern of selection
      of tumor cell types in primary tumors. However, metastases were derived from a
      cell type that was present in the corresponding primary tumor. In addition,
      novel, karyotypically distinct cell types also appeared in the metastatic
      nodules. Markers that appeared in metastases included two translocations,
      t(10;18) and t(1;19). By injecting a mixture of cells from a metastatic nodule
      with a non-metastatic clone into mice, we showed that the new cell types in
      metastases displayed a stable increased growth and metastatic potential when
      compared to the non-metastatic clone, or when compared to the initial cell type
      from which the metastases derived. These results indicate that metastases are
      derived from a distinct cell type in the primary tumor, but that additional
      chromosome and cell evolution occurs, resulting in new cell types that are
      selected in metastases.

PMID- 1377935
TI  - Linkage map of a region of human chromosome band 11q13 amplified in breast and
      squamous cell tumors.
AB  - DNA amplification involving markers on human chromosome band 11q13 is a
      consistent feature of several major cancers, notably adenocarcinoma of the breast
      and squamous cell carcinoma of the head, neck, lung, and esophagus. Since the
      presence of the amplification may be clinically significant, by defining a subset
      of patients at increased risk, it is important to establish which of the several
      genes on the amplified DNA provides the selective force. Here we describe a
      physical map of the centromeric end of the amplified DNA as it exists in a
      particular squamous carcinoma cell line (UMSCC2) and establish an unambiguous
      order for several known markers in the region, including pMS51/D11S97,
      pHB159/D11S146, BCL1, PRAD1/D11S287, HSTF1/FGF4 and INT2/FGF3. Significantly,
      PRAD1 is within 120-150 kb of the BCL1 translocation breakpoint and the data
      identify a new CpG island (D11S814) between PRAD1 and HSTF1. The ordering of the
      HSTF1 and INT2 genes and the clustering of CpG islands in the region have
      important implications in assessing whether the frequently observed
      amplifications at 11q13 are centered on one or more genes.

PMID- 1377937
TI  - Malignant fibrous histiocytoma of the brain in a six-year-old girl.
AB  - We have prepared karyotypes from a malignant fibrous histiocytoma (MFH) of the
      brain of a 6-year-old girl. Sporadic cases of MFH in the central nervous system
      have been reported. However, to our knowledge, this is the first central nervous
      system tumor to be subjected to cytogenetic analysis. The tumor demonstrated a
      complex karyotype, with a variety of numerical and structural abnormalities.
      Although no specific cytogenetic abnormality was observed, the karyotype of this
      case was similar to those reported for adult MFH of soft tissues.

PMID- 1377936
TI  - dup(12)(q13----qter) in two t(14;18)-negative follicular B-non-Hodgkin's
      lymphomas.
AB  - Two t(14;18)-negative follicular B-non-Hodgkin's lymphomas with the same
      chromosomal abnormality, dup(12)(q13----qter), are presented. The absence of a
      BCL2 gene rearrangement was confirmed by molecular studies in both cases.
      Instead, duplication of a 12q segment was found. Further evidence for the
      presence of the dup(12)(q13----qter) was found using fluorescence in situ
      hybridization. dup(12q) may be equivalent to the trisomy 12 originally described
      in B-chronic lymphocytic leukemia. This chromosome anomaly has also been reported
      in B-non-Hodgkin's lymphomas, usually in association with other chromosome
      anomalies and a more aggressive tumor phenotype. Occurrence of dup(12q) in two
      histologically similar cases of follicular small cleaved-cell lymphoma without a
      typical t(14;18), suggests that this karyotypic change may play a critical role
      in some cases of follicle center-cell lymphomas.

PMID- 1377938
TI  - Detection of amplified DNA sequences in human tumor cell lines by fluorescence in
      situ hybridization.
AB  - An unambiguous and rapid characterization of amplified DNA sequences in tumor
      cells is important for the understanding of neoplastic progression. This study
      was conducted to evaluate the potential of fluorescence in situ hybridization
      (FISH) to identify such amplified DNA sequences in human tumor cell lines.
      Applying this technique, we followed the metaphase location and interphase
      position of amplified DNA sequences corresponding to the SAMK, MYC, and MYCN
      genes in four cell lines derived from human tumors: two gastric carcinoma lines
      (KATO III and SNU-16), a neuroblastoma (NUB-7), and a neuroepithelioma (NUB-20)
      line. In metaphase cells of KATO III, NUB-7, and NUB-20 lines, the amplified
      regions were clearly visible and easily identified at an intrachromosomal
      location: in KATO III and NUB-7 at a terminal position and in NUB-20 at an
      interstitial position. In SNU-16, on the other hand, the amplified SAMK and MYC
      sequences were identified in extrachromosomal double minute chromosomes (DMs). In
      this line, the SAMK and MYC sequences were coamplified in the same cells and were
      colocated on the same DMs. FISH also allowed the identification of amplified DNA
      sequences in nondividing cells, enabling us to distinguish, at interphase,
      whether the amplification gave rise to intrachromosomal amplified regions (IARs)
      or to extrachromosomal DMs. The FISH technique also allowed us to determine at
      metaphase as well as at interphase the extent of amplification and the size of
      the IARs.

PMID- 1377939
TI  - Chromosome studies in plasma cell leukemia and multiple myeloma in
      transformation.
AB  - Four patients with plasma cell leukemia (PCL) and two with multiple myeloma (MM)
      in transformation had complex numerical and structural chromosome abnormalities.
      From data published in the literature, the cytogenetic patterns of 46 cases of
      PCL or MM in the leukemic phase are compared with chromosomal abnormalities found
      in MM. Although the spectrum of chromosomal abnormalities is comparable in both
      diseases, the incidence of chromosome abnormalities is higher in PCL than in MM.
      Hypodiploidy with monosomies for chromosomes 13, 16, 17, and 18 is also more
      frequent in PCL than in MM. A mutation within the TP53 gene was detected in one
      of the three patients studied molecularly.

PMID- 1377940
TI  - Rearrangements of chromosome arm 3q in poorly differentiated nasopharyngeal
      carcinoma.
AB  - Cell lines were established from fresh tumor biopsies from two Saudi patients
      with poorly differentiated nasopharyngeal carcinoma (NPC). Cytogenetic analysis
      on Giemsa-banded metaphase cells revealed complex, abnormal karyotypes in both
      patients with modal chromosome numbers of 77 and 52. A der(3)dup(3)(q25-q2?7) or
      t(3;?)(q27;?) was observed in both cell lines. The rearrangements involving
      chromosomes X, 1, 4, 6, 7, 8, 12, 13, 15, 17, and 22 in the first patient and 1,
      6, and 22 in the second patient could represent clonal evolution.

PMID- 1377941
TI  - Hyperdiploidy arising from near-haploidy in childhood acute lymphoblastic
      leukemia.
AB  - Acute lymphoblastic leukemia (ALL) of childhood is frequently characterized by a
      hyperdiploid karyotype. Typically, most of the affected chromosomes in the
      abnormal clone are present in three copies. We have studied two patients with
      hyperdiploid ALL whose leukemic cells were atypical in that all or most of the
      chromosomes were present in either two or four copies, raising a suspicion that
      the observed karyotype arose through duplication of chromosomes in a precursor
      cell with a near-haploid chromosome number. Analysis of restriction fragment
      length polymorphisms confirmed that both cases arose from a near-haploid cell;
      all informative disomic chromosomes tested had loss of heterozygosity.
      Furthermore, the hyperdiploid karyotypes did not arise via a perfect haploid cell
      with exactly 23 chromosomes, because tetrasomic chromosomes remained
      heterozygous. These two patients probably are classified best as near-haploid
      cases, which often are observed to have a co-existing hyperdiploid clone with a
      duplicated chromosome set. The distinction between typical hyperdiploidy and
      hyperdiploidy arising via a near-haploid cell may be clinically important,
      because the prognosis for patients with a hyperdiploid karyotype is favorable in
      comparison to that of patients with a near-haploid karyotype.

PMID- 1377942
TI  - Loss of NF1 alleles in phaeochromocytomas from patients with type I
      neurofibromatosis.
AB  - Type I neurofibromatosis (NF1) is a common autosomal dominant disorder that
      affects tissues derived from the neural crest. The manifestations are varied,
      comprising generalised disorders of growth and development as well as an
      increased risk of benign and malignant tumours including phaeochromocytomas and
      neurofibrosarcomas. The NF1 locus has been mapped to chromosome bands 17q11-12,
      and recently the NF1 gene has been cloned. Deletions identified in the
      constitutional genotype of some patients have suggested that the NF1 phenotype
      may arise from loss of function mutations of the NF1 gene, consistent with the
      hypothesis that it is a tumour suppressor gene. To date, however, analysis of NF1
      tumours has not revealed the frequent allele losses encompassing the NF1 locus,
      implying loss of the wild-type NF1 allele, which would support this hypothesis.
      We report allele losses with markers flanking the NF1 region in each of 7 NF1
      phaeochromocytomas. In each of the 3 tumours for which this could be determined,
      the loss involved the wild-type chromosome. These results provide strong evidence
      that, in cells of the adrenal medulla at least, the NFI gene may act as a tumour
      suppressor.

PMID- 1377943
TI  - Molecular confirmation of BCR-ABL fusion in a chronic myeloid leukemia with a
      complex translocation involving chromosomes 9, 15, and 22.
AB  - We performed molecular studies to resolve the status of BCR and ABL in the bone
      marrow cells of a CML patient with a Ph chromosome resulting from a complex
      translocation involving chromosomes 9, 15, and 22. DNA digestion with BamHI,
      HindIII, and BglII, followed by hybridization to a bcr-specific 32P-labeled
      probe, showed a rearranged banding pattern confirming the involvement of the bcr
      locus in the translocation. Furthermore, total cellular RNA isolated from the
      marrow was subjected to reverse transcription into cDNA and amplified by PCR with
      primers specific for BCR-ABL fusion cDNA. The amplified products obtained from
      this patient and from a CML patient with the standard t(9;22) were both of the
      expected length of approximately 317 bp.

PMID- 1377944
TI  - Translocation t(5;19): a recurrent change in thyroid follicular adenoma.
AB  - The cytogenetic study of a follicular thyroid adenoma revealed a
      t(5;19)(q13;q13.3). This is the second report of a translocation between
      chromosomes 5 and 19 in a thyroid follicular adenoma.

PMID- 1377945
TI  - Conserved patterns of somatic mutation and secondary VH gene rearrangement create
      aberrant Ig-encoding genes in Epstein-Barr virus-transformed and normal human B
      lymphocytes.
AB  - Expression of N-terminal-truncated Ig heavy chains without normal light chain
      expression has been shown to occur in human B cell tumor lines, and to be due to
      diverse types of structural alteration within the expressed Ig heavy and light
      chain genes. Due to the tumor cell origin of these lines, generation of aberrant
      Ig-encoding genes may only occur after malignant transformation, reflecting the
      release of the tumor B cell from the need to express functional Ig for continued
      clonal proliferation. The genetic basis for expression of VH-truncated mu chains
      without light chains in several Epstein-Barr virus (EBV)-transformed human B cell
      lines was investigated with the aim that this information would lead to detection
      of similarly aberrant Ig genes in normal human B lymphocytes. Analysis of the
      productive mu genes in three truncated mu-only human B cell lines showed a
      consistent structural change where a secondary VH-VHDJH gene rearrangement had
      occurred. The site of VH-VH joining was suggestive of a V(D)J recombinase
      mediated event. A consistent pattern of mutation was also observed in the normal
      sized, but non-functional kappa light chain transcripts, making them incapable of
      coding for a functional kappa chain. Using genomic DNA from peripheral blood
      lymphocytes of a donor whose B cells were originally used to make one of the
      truncated mu-only EBV B cell lines, a similarly mutated V kappa gene was detected
      and a similar composite VH-VH gene was cloned. The lack of such aberrant VH and V
      kappa genes in non-lymphoid cells of this individual showed that the structural
      abnormalities in the expressed Ig genes arose somatically during development of
      that B cell clone. The presence of these altered Ig heavy and light chain genes
      in the genomic DNA of untransformed lymphocytes also shows that generation of
      such variant B cell clones can be a pre-neoplastic event and occurs by genetic
      mechanisms active during normal B cell development.

PMID- 1377946
TI  - The hinge region of the CD8 alpha chain: structure, antigenicity, and utility in
      expression of immunoglobulin superfamily domains.
AB  - The lymphocyte surface CD8 antigen is a heterodimer with each chain containing a
      single Ig-related domain, a hinge-like sequence, a transmembrane segment, and a
      short cytoplasmic sequence. A soluble form of the rat CD8 alpha chain was
      produced by introducing a stop codon into the cDNA at the end of the region
      encoding the extracellular sequence and expressed in Chinese hamster ovary cells.
      sCD8 alpha was produced at 20 mg/l, and consisted of monomers, dimers, and higher
      aggregates. The latter could be minimized, but not eliminated, by removal of one
      of the two cysteine residues in the hinge region by mutation and by growth in
      serum-free medium. The positions of the N- and O-linked glycosylation sites and
      the disulphide bond in the Ig-like domain were determined. The MRC OX-8 antibody
      was shown to react with a region from the CD8 alpha hinge containing 24 amino
      acids and the antigenic determinant was sensitive to neuraminidase digestion. A
      construct encoding the Ig-like domain of rat CD8 alpha without the hinge was not
      expressed in CHO cells, indicating the importance of the hinge region for
      expression. It seemed possible that the CD8 alpha hinge might facilitate
      expression of other Ig-related domains and such expression could be detected
      using the MRC OX-8 antibody. To test the system cDNA constructs were made with
      the rat CD8 alpha hinge spliced to the V-like domain of mouse CD8 alpha, to the V
      alpha and V beta domains of a T lymphocyte antigen receptor, and to one or both
      of the Ig-like domains of the MRC OX-47 membrane antigen. All these forms were
      expressed as soluble proteins that were detected with the MRC OX-8 antibody. This
      method may prove useful for the expression of Ig superfamily domains for raising
      antibodies and other studies.

PMID- 1377947
TI  - The ontogeny and functional characteristics of human B-1 (CD5+ B) cells.
AB  - We demonstrate that, on average, greater than 90% of B lymphocytes in fetal
      spleen express CD5 at gestational ages of 17-23 weeks. Similarly, CD5+ B cells (B
      1 cells) are the major B cell subset in umbilical cord blood. These findings
      depend on the optimization of fluorochrome conjugated anti-CD5 reagents for
      multiparameter fluorescent-activated cell sorter (FACS) analysis. From infancy
      through childhood the percentage of B-1 cells gradually diminishes in both spleen
      and peripheral blood. Stable adult levels, 25-35% of the total B cell population,
      are reached in late adolescence. The decrease in the percentage of B-1 cells in
      spleen is accompanied by an increase in conventional (CD5-) B cells, keeping the
      percentage of total B cells per mononuclear cells relatively constant. In
      contrast, in peripheral blood, the concentration of both B-1 cells and total B
      cells decreases, while T cells increase. At the functional level, we show that
      polyreactive IgM autoantibodies are produced by FACS-sorted CD5high B cells, but
      not by CD5- B cells from adolescent spleen. In contrast, fetal splenic CD5high
      and CD5- B cells appear functionally uniform, both producing IgM autoantibodies
      that are typical of B-1 cells. The apparent level of CD5- B cells in fetal
      spleen, on average 10% of total B cells, may still result from limitations of our
      reagent. The prominence of B-1 cells in fetal spleen and cord blood, the gradual
      reduction of B-1 cells with increasing age, and its characteristic repertoire,
      all suggest a role for this cell type in immunologically immature hosts.

PMID- 1377948
TI  - Antibodies of HIV-1 positive subjects and experimentally immunized primates and
      rodents bind to sequence divergent regions of the third variable domain (V3) of
      gp120.
AB  - Several motifs have been found to be the target of the neutralizing antibody
      response to HIV, the human immunodeficiency virus. One of the well characterized
      motifs maps to a loop within the third hypervariable region (V3) of the exterior
      envelope glycoprotein gp120 at amino acid positions 308-331 and is referred to as
      the principal neutralizing determinant (PND). The sequence of this V3 loop raises
      the question of the immunogenicity and the degree of diversity of the antibody
      response to the PND. We show here that this neutralization-related motif is
      highly immunogenic in HIV-positive subjects and in experimentally immunized
      primates and rodents submitted to various anti-HIV immunization regimens. In
      probing the diversity of the antibody response to PNDs corresponding to 11 HIV
      sequence-divergent isolates in serum samples of 101 HIV-positive individuals we
      found that human antibodies exhibit binding affinity to up to nine PND synthetic
      peptides. This antibody binding was in all cases tested inhibitable by the
      homologous PND synthetic peptide. We additionally demonstrate that this antibody
      cross-reactivity towards sequence-divergent PNDs is detectable in the sera of
      mice and chimpanzees experimentally immunized against a single HIV-1 isolate.
      Finally, we noticed that there is a hierarchy of reactivity among the various
      PNDs wherein the synthetic peptide corresponding to the MN isolate was generally
      the most prominently recognized by antibodies of human, non-human primate, and
      rodent origins. Based on these findings and on features of the sequences analyzed
      we suggest that, despite its overall sequence variability, the PND encompasses
      conserved amino acid positions or epitopes that are the targets of antibodies
      recognizing sequence-divergent isolates. We also propose that the high positive
      charge density of the most frequently recognized PNDs and the high antigenicity
      value of some of their residues are critical to the broad immunoreactivity of
      this neutralization-related motif.

PMID- 1377949
TI  - Contribution of the digestive tract microflora to amylomaize starch degradation
      in the rat.
AB  - To study in vivo the contribution of the bacterial flora to amylomaize starch
      degradation in the rat, germ-free and conventional rats were fed on a diet
      containing either a normal maize starch or an amylomaize starch. In germ-free
      rats maize starch was almost totally digested in the small intestine, whereas 40%
      of the ingested amylomaize starch reached the caecum and 30% was excreted,
      despite the very high endogenous amylase activity. Study by transmission electron
      microscopy of germ-free caecal contents showed an endocorrosion of the starch
      granule. In conventional rats, as in germ-free rats, digestibility of maize
      starch reached 98% in the small intestine, whereas that of amylomaize starch was
      only 60%. In the caecum of these rats amylomaize starch was fermented, and this
      led to a decrease in caecal pH and to formation of short-chain fatty acids
      (SCFA), especially propionate. Comparison between conventional rats fed on maize
      starch or amylomaize starch showed that caecal SCFA concentrations during a
      circadian cycle varied in the same way whereas total SCFA and lactic acid
      concentrations were much higher in rats fed on amylomaize starch. Amylase (EC
      3.2.1.1) activity was similar in the caecal contents of conventional rats
      whatever the ingested starch. It was lower in conventional than in germ-free
      rats, but no starch granule remained in the caecum of conventional rats. These
      results showed that bacterial amylase was more efficient at degrading resistant
      amylomaize starch than endogenous amylase.

PMID- 1377950
TI  - Endothelial adhesion molecules in heart transplantation.

PMID- 1377951
TI  - The effect of sphingosine and phorbol ester on the signal transduction enzymes
      and fibronectin release in cell culture.
AB  - In testing the hypothesis that the stimulation of the release of fibronectin (FN)
      by 12-O-tetradecanoylphorbol 13-acetate (TPA) from human lung fibroblasts in
      culture is the result of activation of protein kinase C (PKC), we found that the
      PKC inhibitor sphingosine strongly inhibited FN release in presence and even in
      absence of TPA. However, a different PKC inhibitor, calphostin C, despite almost
      complete inhibition of PKC, had no effect on FN release. We concluded that
      sphingosine is a potent inhibitor of FN release from the cell surface,
      independent of its inhibition of PKC; and that TPA stimulates release of FN by a
      pathway other than activation of PKC. We found that the activation of PKC by TPA
      was accompanied by inhibition of the cAMP-dependent protein kinase (PKA). When
      PKA was inhibited by an antagonist (H8, a cAMP analogue) at a concentration
      specific for PKA inhibition, the release of FN was stimulated similar to the
      stimulation with TPA. Activation of PKA with forskolin resulted in decreased FN
      release. In conclusion, we have shown that: (1) sphingosine had a robust effect
      inhibiting the release of FN from fibroblasts, independent of its action on PKC;
      (2) TPA treatment of these cells resulted in inhibition of PKA; (3) inhibition of
      PKA stimulated FN release whereas its activation decreased this release. It is
      possible that PKA, by phosphorylating a protein, may function, directly or
      indirectly, in keeping FN attached to the cell surface of fibroblasts.

PMID- 1377952
TI  - Pseudo-obstruction in children.
AB  - Pseudo-obstruction of the gastrointestinal tract is a rare disorder of impaired
      gastrointestinal motility. The more common symptoms of pseudo-obstruction in the
      infant or child include dysphagia, nausea, vomiting, abdominal distention,
      abdominal pain, and constipation. The majority of children have symptoms within
      the first year of life. Chronic cases of pseudo-obstruction are associated with
      neuropathic or myopathic changes in other parts of the body. Bladder dysfunction
      and neurological problems have been reported. The diagnosis of pseudo-obstruction
      is based on history, physical examination, radiographic studies and motility
      studies. Advances in medical technology have facilitated the identification of
      abnormal motility patterns in children. Therapy for pseudo-obstruction is
      primarily supportive. The use of motility agents has been unsuccessful in
      treating pseudo-obstruction. Nutritional and antibiotic therapy are the mainstays
      of treatment. Nursing interventions, patient/family education and advances in
      home care technology have improved the quality of life for children with pseudo
      obstruction. Small bowel transplantation offers hope for the future.

PMID- 1377954
TI  - Endothelin modulation of tissue plasminogen activator release from human vascular
      endothelial cells in culture.
AB  - To clarify a possible involvement of the vasoconstrictive peptide endothelin in
      the regulation of endothelial cell-mediated fibrinolytic system, confluent
      cultures of vascular endothelial cells from human umbilical vein were incubated
      in serum-free medium in the presence of endothelin-1 at 100 nM and below, and
      tissue plasminogen activator antigen (t-PA:Ag) in the medium was determined by
      enzyme immunoassay. Endothelin-1 at 1 nM and above significantly decreased the
      release of t-PA:Ag from the endothelial cells after a 24 h incubation. The t
      PA:Ag release was also decreased by either endothelin-2 or endothelin-3 at 10 nM.
      The activity of lactate dehydrogenase in the medium was not changed by endothelin
      1 at 100 nM and below, suggesting that the peptide did not cause nonspecific cell
      damage. The decrease in the t-PA:Ag release induced by endothelin-1 occurred in
      the presence or absence of 8-bromo cyclic AMP, which is an active congener of
      cyclic AMP; 3-isobutyl-1-methylxanthine, which is an inhibitor of
      phosphodiesterase; and forskolin, which is a stimulator of adenylate cyclase.
      These results strongly indicated that cyclic AMP which is known to down-regulate
      t-PA:Ag release was not involved in the endothelin-1 effect. However, endothelin
      1 failed to decrease the t-PA:Ag release in the presence of either calcium
      ionophore A23187 or EGTA; the ionophore itself markedly decreased the release.
      The cytosolic calcium accumulation was significantly increased by endothelin-1.
      These results suggest that endothelin-1 decreases the release of t-PA:Ag from
      human endothelial cells through an excess accumulation of intracellular,
      especially cytosolic which would be mediated by an extracellular, calcium
      dependent mechanism.

PMID- 1377953
TI  - Combination of recombinant cytokines fails to produce ex vivo expansion of human
      blood hematopoietic progenitor cells.
AB  - The concept of ex vivo expansion of the human progenitor cell population was
      tested in this study. In the presence of interleukin-3 and -6 we compared the
      abilities of various liquid culture conditions of human blood-derived
      hematopoietic progenitor cells to yield a suitable condition for the expansion of
      blood progenitor cells. Although the best result was obtained in the
      gastpermeable bag culture system, the enhancement effect (maximum of 3.8-fold for
      granulocyte/macrophage colony-forming units and 3.0-fold for erythroid burst
      forming units) lasted for only a short period (less than 6 d). The results of
      this study are disappointing for clinical use, and attempts with currently
      available technology appear to be limited in their potential.

PMID- 1377955
TI  - Studies on the mechanism of binding of serpins and serine proteases.
AB  - The serpin family of inhibitors have an important role in the control of
      coagulation and fibrinolysis. For a full understanding of how these pathways
      operate in vivo and correct measurement of enzyme and inhibitor activity, in
      vitro knowledge of the mechanism of action of serpins is essential. Using alpha 2
      antiplasmin as a model inhibitor we find, in contrast to most previous reports, a
      reversible mechanism: E + I in equilibrium with EI in equilibrium with EI', where
      complex formation is two stepped, but both steps are reversible. Our work with
      plasmin in the presence of 50 mM aminohexanoic acid shows that binding of alpha 2
      antiplasmin is very tight (but reversible) with an overall Ki (Ki final) = 4.0
      pM. With chymotrypsin (a model serine protease) Ki final = 100 pM, so as expected
      binding of alpha 2-antiplasmin is weaker with chymotrypsin. However, analysis of
      the individual rate constants shows that the difference in strength of binding is
      accounted for by the dissociation rate constant for the second step (k-2) = 1.9 x
      10(-6) s-1 for plasmin and 1.1 x 10(-4) s-1 for chymotrypsin. Thus k-2, the rate
      constant previously ignored, explains the different affinities of alpha 2
      antiplasmin for these two enzymes. Furthermore, this model of two (or more) step,
      reversible binding is accepted for protease inhibitors of other families. With
      one of these, aprotinin (a Kunitz inhibitor) with plasmin we also obtain a two
      stage reversible mechanism with a Ki final = 200 pM and the strength of
      inhibition is also largely determined by k-2 = 3.5 x 10(-5) s-1.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1377956
TI  - Aprotinin in cardiopulmonary bypass--effects on the Hageman factor (FXII)-
      Kallikrein system and blood loss.
AB  - Aprotinin has been used in our hospital in open heart surgery for almost 20 years
      and recently published studies have revealed a reduction in postoperative blood
      loss under this therapy. In the present study patients undergoing aorto-coronary
      bypass operations received either 20,000 KIU aprotinin/kg body weight (group 2)
      or 60,000 KIU aprotinin/kg body weight (group 3). Another group of patients
      without aprotinin served as a control (group 1) and postoperative bleeding was
      more pronounced in these patients compared with the other groups. In parallel,
      slight reductions in kallikrein-like activity were observed in patients treated
      with aprotinin. Furthermore, we have shown that the main inhibitor of the contact
      phase, C1-esterase-inhibitor, loses some of its activity against beta-FXIIa in
      the presence of heparin. Aprotinin was able to partly antagonize this phenomenon.
      All studies dealing with the effect of aprotinin in extracorporeal circulation
      demonstrate hyperfibrinolysis in untreated patients. Aprotinin is known to
      inhibit plasmin at low concentrations and thus reduced the postoperative bleeding
      tendency (group 2). In addition, plasma kallikrein is inhibited by high aprotinin
      concentrations and is responsible for a reduced activation of the contact phase
      system. This effect led to a further reduction in blood loss (group 3).

PMID- 1377957
TI  - Serotonergic, noradrenergic and galaninergic projections to the nucleus
      parafascicularis.
AB  - Immunocytochemical staining for serotonin (5-HT), tyrosine hydroxylase (TH) and
      galanin (GAL) was combined with horseradish peroxidase (HRP) retrograde tract
      tracing technique to analyze the localizations of 5-HT-, catecholamine (CA)- and
      GAL-containing neurons in the brainstem which project to the nucleus
      parafascicularis (PF) in rats. It is demonstrated that most of the retrogradely
      HRP-labeled neurons (70%) in bilateral periaqueductal gray (PAG) and raphe nuclei
      are positively immunostained by antiserum to 5-HT, and that most of the
      retrogradely HRP-labeled neurons (over 80%) in bilateral locus coeruleus (LC) are
      positively immunostained by antisera to both TH and GAL. The possible functions
      of these PF-petal serotonergic, catecholaminergic (actually noradrenergic) and
      galaninergic projections are discussed.

PMID- 1377958
TI  - Modulation of the behavioural effects of interleukin-1 in mice by nitric oxide.
AB  - Interleukin-1 is a cytokine which mediates the host response to infection and
      inflammation and is responsible for sickness behaviour. Inhibition of nitric
      oxide synthase activity by N omega nitro-L-Arginine-Methyl-ester (30 mg kg-1,
      i.p.) potentiated the depressive effects of interleukin-1 (375 ng, i.p.) on
      social investigation in mice. This effect was attenuated by L-arginine (180 mg kg
      1, i.p.) but not by D-arginine. The same treatment did not alter the body weight
      loss induced by interleukin-1. These results suggest that nitric oxide plays a
      protective role in the neural effects of interleukin-1.

PMID- 1377959
TI  - The identification of leaf thionin as one of the main jasmonate-induced proteins
      of barley (Hordeum vulgare).
AB  - Jasmonic acid (JA) and its methyl ester (JA-Me) are able to introduce the
      accumulation of several specific polypeptides in cut leaf segments of barley. Two
      of the most prominent JA-induced proteins of M(r) 15,000 and 23,000 have been
      characterized by isolating and sequencing complete cDNA sequences. While the
      sequence of the M(r) 23,000 polypeptide shows no similarity to published
      sequences, the sequence of the M(r) 15,000 polypeptide corresponds to the higher
      molecular-weight precursor of a leaf thionin previously characterized.
      Transcripts for the M(r) 23,000 and M(r) 15,000 polypeptides accumulate in leaf
      segments shortly after the beginning of JA treatment. JA and JA-Me induce the
      appearance of the two proteins not only in leaf segments but also in intact
      barley seedlings. However, in seedlings the accumulation of JA-induced proteins
      occurs much more slowly and requires high concentrations of volatile JA-Me. Thus,
      in barley it seems unlikely that volatile JA-Me is involved in the interaction
      between different members of this species, as has been proposed recently for
      tomato seedlings.

PMID- 1377960
TI  - Molecular details of tomato extensin and glycine-rich protein gene expression.
AB  - In a recent publication (Plant Molecular Biology 16: 547-565 (1991)), Showalter
      et al. described the isolation and initial characterization of fifteen extensin
      and extensin-like tomato cDNAs. These cDNAs were determined to fall into five
      distinct classes; class I and II clones encoded extensins, class III and V clones
      encoded glycine-rich proteins (GRPs), and class IV clones encoded a portion of a
      GRP sequence on one DNA strand and a portion of an extensin sequence on the other
      DNA strand. In this publication, a more detailed analysis of the expression of
      these cDNA classes was performed with respect to wounding in various tomato
      organs, development, kinetics and systemic extent of the wound response, ethylene
      treatment, abscisic acid (ABA) treatment, and drought stress by using RNA gel
      blot hybridizations. In general, extensin gene expression was readily detected in
      stems and roots, but not in leaves. With both class I and II extensin cDNA
      probes, wound-induced accumulation of mRNA in stems was first detected between 4
      and 8 h after wounding with maximal accumulation occurring after 12 h. Moreover,
      these extensin wound responses were detected locally at the wound site but not
      systemically. Expression of the class III GRP was largely limited to wounded stem
      tissue. Initial detection and maximal accumulation of the class III GRP mRNA was
      similar to the extensins mRNAs; however, this GRP wound response occurred both
      locally and systemically. Additionally, abscisic acid treatment and drought
      stress resulted in the marked accumulation of the class III GRP mRNA in tomato
      stems, but did not alter the expression of the other cDNA classes. In contrast,
      expression of the class V GRP occurred in stems and roots and to a lesser extent
      in leaves and decreased in response to wounding over a 24 h time period. The
      class V GRP wound response was further characterized by an early, transient
      accumulation of mRNA occurring 2-4 h after wounding in stems and by its local
      nature.

PMID- 1377961
TI  - An ethylene-related cDNA from ripening apples.
AB  - We report the isolation of a ripening-related apple cDNA which is complementary
      to a mRNA which may be involved in ethylene production. Poly(A)+ RNA was
      extracted from cortical tissue of ripe apple fruit (Malus domestica Borkh cv.
      Golden Delicious) and a cDNA library constructed in the plasmid vector pSPORT.
      The library was screened with pTOM13, a tomato cDNA clone thought to code for ACC
      oxidase in that fruit. An apple cDNA clone (pAP4) was isolated and sequenced. The
      1182 bp cDNA insert includes an open reading frame of 942 bp, and shows strong
      homology with reported tomato and avocado sequences, both at the nucleic acid and
      amino acid levels. The polypeptide has a calculated molecular mass of 35.4 kDa
      and a calculated pI of 5.15. In apple cortical tissue, expression of pAP4
      complementary RNA increased with ethylene production by the fruit during
      ripening. Expression was also enhanced in both ethylene-treated and wounded
      fruit.

PMID- 1377963
TI  - The isolation and characterisation of a cDNA clone encoding L-asparaginase from
      developing seeds of lupin (Lupinus arboreus).
AB  - An L-asparaginase cDNA clone, BR4, was isolated from a Lupinus arboreus Sims
      developing seed expression library by screening with polyclonal antibodies to the
      seed asparaginase. The cDNA hybridised with an oligonucleotide probe designed
      from amino acid sequence data and was found on sequencing to be 947 bp in length.
      Six polypeptide sequences obtained previously could be placed along the longest
      open reading frame. Computer-aided codon use analysis revealed that the cDNA
      sequence was consistent with other plant genes in terms of codon use. The cDNA
      insert was used to analyse asparaginase transcription in various tissues by
      northern blot analysis. A transcript size of approximately 1.2 kb was detected in
      L. arboreus seed total and poly(A)+ RNA. The level of this transcript declined
      from 30 days after anthesis to an undetectable level by day 55. Furthermore,
      under the high stringency conditions used, the seed asparaginase cDNA did not
      hybridise with total or poly(A)+ RNA isolated from root tips, suggesting that the
      asparaginase known to be present in this tissue may be the product of a different
      gene. Southern analysis suggested the seed asparaginase is a single-copy gene.
      The plant asparaginase amino acid sequence did not have any significant homology
      with microbial asparaginases but was 23% identical and 66% similar (allowing for
      conservative substitutions) to a human glycosylasparaginase.

PMID- 1377962
TI  - Nucleotide sequence of a tobacco cDNA encoding plastidic glutamine synthetase and
      light inducibility, organ specificity and diurnal rhythmicity in the expression
      of the corresponding genes of tobacco and tomato.
AB  - A full-length cDNA encoding glutamine synthetase (GS) was cloned from a lambda
      gt10 library of tobacco leaf RNA, and the nucleotide sequence was determined. An
      open reading frame accounting for a primary translation product consisting of 432
      amino acids has been localized on the cDNA. The calculated molecular mass of the
      encoded protein is 47.2 kDa. The predicted amino acid sequence of this precursor
      shows higher homology to GS-2 protein sequences from other species than to a leaf
      GS-1 polypeptide sequence, indicating that the cDNA isolated encodes the
      chloroplastic isoform (GS-2) of tobacco GS. The presence of C- and N-terminal
      extensions which are characteristic of GS-2 proteins supports this conclusion.
      Genomic Southern blot analysis indicated that GS-2 is encoded by a single gene in
      the diploid genomes of both tomato and Nicotiana sylvestris, while two GS-2 genes
      are very likely present in the amphidiploid tobacco genome. Western blot analysis
      indicated that in etiolated and in green tomato cotyledons GS-2 subunits are
      represented by polypeptides of similar size, while in green tomato leaves an
      additional GS-2 polypeptide of higher apparent molecular weight is detectable. In
      contrast, tobacco GS-2 is composed of subunits of identical size in all organs
      examined. GS-2 transcripts and GS-2 proteins could be detected at high levels in
      the leaves of both tobacco or tomato. Lower amounts of GS-2 mRNA were detected in
      stems, corolla, and roots of tomato, but not in non-green organs of tobacco. The
      GS-2 transcript abundance exhibited a diurnal fluctuation in tomato leaves but
      not in tobacco leaves. White or red light stimulated the accumulation of GS-2
      transcripts and GS-2 protein in etiolated tomato cotyledons. Far-red light
      cancelled this stimulation. The red light response of the GS-2 gene was reduced
      in etiolated seedlings of the phytochrome-deficient aurea mutant of tomato. These
      results indicate a phytochrome-mediated light stimulation of GS-2 gene expression
      during greening in tomato.

PMID- 1377964
TI  - Activation of flavonoid biosynthesis in roots of Vicia sativa subsp. nigra plants
      by inoculation with Rhizobium leguminosarum biovar viciae.
AB  - Infective (nodulating) Rhizobium leguminosarum biovar viciae (R.l. viciae)
      bacteria release Nod factors which stimulate the release of nodulation gene
      inducing flavanones and chalcones from roots of the host plant Vicia sativa
      subsp. nigra (K. Recourt et al., Plant Mol Biol 16: 841-852; H.P. Spaink et al.,
      Nature 354: 125-130). The hypothesis that this release results from increased
      synthesis of flavonoids was tested by studying the effect of inoculation of V.
      sativa with infective and uninfective R.l. viciae bacteria on (i) activity of L
      phenylalanine ammonia-lyase, (ii) level of chalcone synthase mRNA, and (iii)
      activity of (eriodictyol) methyltransferase in roots. Consistent with the
      hypothesis, each of these parameters was found to increase 1.5 to 2-fold upon
      inoculation with infective R.l. viciae bacteria relative to the situation for
      uninoculated roots and for roots inoculated with uninfective rhizobia.

PMID- 1377965
TI  - Cloning and expression of an embryo-specific mRNA up-regulated in hydrated
      dormant seeds.
AB  - Dormant seeds do not germinate when imbibed in water even when conditions are
      favorable for germination. These hydrated seeds remain viable, but growth
      arrested for weeks due to unknown restrictions within the embryo. As a model
      system for the study of the molecular processes occurring in dormant seeds, we
      have chosen to examine gene expression in Bromus secalinas, a grass species that
      produces seeds with high levels of embryonic dormancy. Using differential
      screening for mRNAs present in hydrated dormant embryos, we have identified a
      cDNA clone, pBS128, that encodes a mRNA transcript found in the embryos of
      hydrated seeds of B. secalinus as well as in embryos from mature dry seeds.
      Striking differences in pBS128 transcript levels appear upon hydration of dormant
      and nondormant seeds. Upon imbibition pBS128 transcript levels increase over four
      fold in dormant seeds, but rapidly decline and disappear in nondormant seeds,
      which subsequently germinate. The pBS128 transcript appears to be embryo-specific
      since the transcript is not detectable in either non-stressed or dehydrated
      seedling tissue. Application of 50 microM ABA to nondormant seeds arrests
      germination and enhances pBS128 transcript levels. The nucleotide sequence of the
      nearly full-length pBS128 cDNA shows no homology to other reported genes, and the
      putative protein sequence does not exhibit the hydrophilic characteristics of the
      ABA-responsive LEA (late embryogenesis abundant) proteins.

PMID- 1377966
TI  - Cloning and characterisation of an oleosin gene from Brassica napus.
AB  - The sequence of an oleosin gene from Brassica napus has been determined. This
      gene contains a single intron of 437 bp and encodes a polypeptide of 195 amino
      acids. The oleosin gene product has an estimated molecular mass of 21.5 kDa and
      consists of a highly hydrophobic central domain flanked by relatively polar N-
      and C-terminal domains. The central domain is highly conserved between all
      oleosins sequenced to date and contains a run of periodically spaced leucine
      residues similar to that of a leucine-zipper motif. The gene has been shown to be
      expressed specifically in the embryo, maximally between 9 and 11 weeks after
      flowering, i.e. during the seed desiccation stage. Two transcriptional start
      sites have been mapped to -70 and -21 of the ATG and a putative ABA-responsive
      element and three repeated motifs have been identified in the promoter. These
      short promoter sequences could correspond to regulatory elements responsible for
      embryo-specific gene expression. Up to six genes exist in the oleosin gene
      family.

PMID- 1377967
TI  - DNA-binding properties of cloned TATA-binding protein from potato tubers.
AB  - A full-length cDNA clone encoding the TATA-binding protein (TBP), the DNA-binding
      component of the general transcription factor TFIID was cloned from potato
      tubers. The DNA sequence of this cDNA indicated that the predicted potato protein
      was very similar to cloned TBP from other species. Genomic southern analysis
      showed that TBP is encoded in the potato genome as a low-copy-number sequence.
      The potato TBP cDNA clone was shown to encode a functional protein that interacts
      in a sequence-specific way with the promoter region of a class-1 potato patatin
      gene. Functional analysis of carboxy-terminal truncated derivatives of potato TBP
      showed that important components of DNA binding were located within the carboxy
      terminal 54 amino acids. Kinetic and thermodynamic properties of in vitro
      synthesised potato TBP were investigated, and demonstrated strict salt and
      temperature preferences for maximum DNA binding activity. In addition on and off
      rate measurements showed that both association and dissociation of TBP from DNA
      is slow. The specific and the non-specific equilibrium constants Ks and Kn were
      calculated as 5 x 10(9) M-1 and 3.65 x 10(4) M-1 respectively. These results
      indicate that the interaction of potato TBP with the patatin promoter is highly
      specific.

PMID- 1377968
TI  - Three genes encode 3-hydroxy-3-methylglutaryl-coenzyme A reductase in Hevea
      brasiliensis: hmg1 and hmg3 are differentially expressed.
AB  - The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyses an
      important step in isoprenoid biosynthesis in plants. In Hevea brasiliensis, HMGR
      is encoded by a small gene family comprised of three members, hmg1, hmg2 and
      hmg3. We have previously described hmg1 and hmg2 (Plant Mol Biol 16: 567-577,
      1991). Here we report the isolation and characterization of hmg3 genomic and cDNA
      clones. In comparison to hmg1 which is more highly expressed in laticifers than
      in leaves, the level of hmg3 mRNA level is equally abundant in laticifers and
      leaves. In situ hybridization experiments showed that the expression of hmg3 is
      not cell-type specific while hmg1 is expressed predominantly in the laticifers.
      Primer-extension experiments using laticifer RNA showed that hmg1 is induced by
      ethylene while hmg3 expression remains constitutive. The hmg3 promoter, like the
      promoters of most housekeeping genes, lacks a TATA box. Our results suggest that
      hmg1 is likely to encode the enzyme involved in rubber biosynthesis while hmg3 is
      possibly involved in isoprenoid biosynthesis of a housekeeping nature.

PMID- 1377970
TI  - Structure of gap junction channels.
AB  - Gap junctions are regions of contact between adjacent cells, consisting of arrays
      of channels linking the cell interiors. The channels are formed by polypeptides
      called connexins; the amino acid sequences of many different connexins are known,
      and they are thought to resemble each other closely in tertiary and quarternary
      structure. Single channels have recently been isolated and purified, and earlier
      evidence has been confirmed showing that they consist of six identical subunits
      arranged around the central pore. Gap junction channels are known to open and
      close in response to changes in ligand concentrations and electrical potential;
      in this respect they are very similar to ligand-gated ion channels which act as
      receptors in the membranes of excitable cells. The similarity is shown to extend
      to structural features such as the amino acid residues lining the pore, and
      perhaps the location of the actual gate.

PMID- 1377969
TI  - Nucleotide sequence of a long cDNA from the rice waxy gene.

PMID- 1377971
TI  - Neurology of language.
AB  - A host of recent investigations and new theoretical models have advanced our
      understanding of the neural underpinnings of speech and language in humans. The
      application of positron emission tomography (PET) techniques to the investigation
      of language has provided corroborating evidence regarding the role of left
      hemisphere structures previously associated with language, together with some
      intriguing new findings. Innovative ideas regarding the ontogeny of language have
      come from studies of deaf infants who appear to babble with signs in much the
      same way that hearing infants babble vocally. A number of investigators have
      focused on the controversial syndrome known as progressive aphasia, and new
      evidence has supported the importance of this syndrome from both diagnostic (e.g.
      providing clues regarding neuropathology) and scientific (e.g. yielding
      information about the organization of lexical access structures in left temporal
      lobe) perspectives.

PMID- 1377973
TI  - Natural history and treatment of multiple sclerosis.
AB  - The course of multiple sclerosis (MS) evolves over decades. Recent advances in
      our understanding of the spectrum and variability of the course of MS over the
      long term in large geographically based populations, and over the short term in
      selected subgroups randomized to the placebo limbs of controlled clinical trials
      are discussed. Trials of several toxic immunosuppressive drugs and plasma
      exchange (PE) show that these methods of treatment are unlikely to help MS
      patients, although azathioprine has some rationale in rapidly advancing cases.
      The triggering of attacks by viral infections makes one await the results of
      current trials of interferon-beta with special interest.

PMID- 1377972
TI  - Susceptibility to experimental allergic encephalomyelitis in animal models of
      autoimmunity.
AB  - Experimental allergic encephalomyelitis (EAE) continues to serve as a useful
      model of organ-specific autoimmunity and as a model for the human demyelinating
      disease, multiple sclerosis. Current studies focus on the role of the various
      cellular components involved in mediating disease, the nature and molecular
      characterization of the immune process, and the target site within the central
      nervous system (CNS). The results of these studies are providing new therapeutic
      rationales.

PMID- 1377974
TI  - Site-directed mutagenesis of catalytic active-site residues of Taka-amylase A.
AB  - The cDNA encoding Taka-amylase A (EC.3.2.1.1, TAA) was isolated to identify
      functional amino acid residues of TAA by protein engineering. The putative
      catalytic active-site residues and the substrate binding residue of TAA were
      altered by site-directed mutagenesis: aspartic acid-206, glutamic acid-230,
      aspartic acid-297, and lysine-209 were replaced with asparagine or glutamic acid,
      glutamine or aspartic acid, asparagine or glutamic acid, and phenylalanine or
      arginine, respectively. Saccharomyces cerevisiae strain YPH 250 was transformed
      with the expression plasmids containing the altered cDNA of the TAA gene. All the
      transformants with an expression vector containing the altered cDNA produced
      mutant TAAs that cross-reacted with the TAA antibody. The mutant TAA with
      alteration of Asp206, Glu230, or Asp297 in the putative catalytic site had no
      alpha-amylase activity, while that with alteration of Lys209 in the putative
      binding site to Arg or Phe had reduced activity.

PMID- 1377975
TI  - Molecular cloning of feline interferon cDNA by direct expression.
AB  - A cDNA sequence coding for feline interferon has been cloned for the first time
      by screening a cDNA library constructed using Okayama-Berg vector and mRNA
      derived from the feline cells (LSA-I) induced by TPA (12-o-tetradecanoylphorbor
      13-acetate) for the ability of transient expression to produce feline interferon
      in COS1 monkey cells. The amino acid sequence, deduced from the nucleotide
      sequence by comparing it with the sequences of other mammalian IFNs, consists of
      171 amino acids with 6 cysteins and an N-glycosylation site at the amino acid
      position 79, and has about 60% homology to human IFN alpha 1. The interferon was
      partially purified through Blue Sepharose, and its molecular weight was estimated
      to be 2.4 x 10(4). The antiviral activity was acid stable, and glycosylation was
      suggested.

PMID- 1377976
TI  - MR imaging characteristics of noncancerous lesions of the prostate.
AB  - Radical prostatectomy specimens from 53 men with clinical stage A or B prostate
      cancer were retrospectively reviewed and compared with correlative axial T2
      weighted magnetic resonance (MR) images obtained just before surgery. Non
      cancerous lesions were evaluated for signal intensity and location. Focal high
      signal-intensity areas (n = 72) were present in 81% of patients. The 26% of
      lesions seen in the central gland all correlated with cystic atrophy. Of the 53
      lesions seen in the peripheral prostate, 47 (89%) were cystic atrophy without
      associated cancer, four (7.5%) cystic atrophy with cancer, and two (3.8%) focal
      inflammation. Focal low-signal-intensity areas (n = 42) were present in 60% of
      patients. Of the 31% of lesions in the central prostate, one-fifth correlated
      with benign prostatic hyperplasia (BPH) and four-fifths with fibrous tissue. Of
      the 69% of peripheral lesions, 83% corresponded to fibrous tissue, 10% to BPH,
      and 7% to normal tissue. Mixed lesions (n = 42) were present in 64% of patients;
      86% of these were located centrally and 14% peripherally. All mixed central
      lesions were BPH; the peripheral lesions were areas of combined cystic atrophy
      and fibrosis. BPH of low or mixed signal intensity can extend into the peripheral
      prostate and mimic cancer. High-intensity cystic atrophy associated with cancer
      can mimic normal tissue.

PMID- 1377977
TI  - Prenatal ontogeny of substance P-like immunoreactivity in the trigeminal spinal
      caudal subnucleus of the human fetus--an immunocytochemical study.
AB  - Using an immunocytochemical method, the prenatal ontogeny of substance P-like
      immunoreactivity (SP-LI) was demonstrated in the trigeminal spinal caudal
      subnucleus (TSCS) of human fetus, fetal age (menstruation age) 11.5-40 weeks. The
      time of initial appearance of SP-LI in the human brainstem TSCS was between the
      fetal age 11.5 weeks and 16 weeks. While the fetus grew, the density of SPLI
      fibers and terminals in the human fetus brainstem TSCS increased constantly from
      fetal age 16 weeks to 40 weeks. These findings indicated that substance P (SP)
      might play an important role in the human trigeminal nerve system development and
      in its functional establishment during the prenatal period.

PMID- 1377978
TI  - A re-examination of the spino-reticulo-diencephalic pathway in the cat.
AB  - One commonly accepted idea is that affective aspects of pain sensation are
      derived from a flow of information from the spinal cord through the reticular
      formation to the intralaminar thalamus and subthalamus. Little is known, however,
      about the extent to which spinoreticular terminations and reticulodiencephalic
      neuronal cell bodies overlap. This study used a combination of anterograde and
      retrograde tracing techniques to compare these distributions in the cat. Whereas
      spinoreticular terminations were concentrated caudally and laterally, neurons
      projecting to intralaminar thalamus and subthalamus were concentrated rostrally
      and medially. Thus, information conveyed from the spinal cord to the reticular
      formation appears to have direct access to intralaminar thalamus and subthalamus
      only by way of a few widely scattered neurons. When considered with the results
      of others, these results encourage less emphasis on a putative spino-reticulo
      diencephalic pathway for pain. Rather, the reticular formation's role in pain is
      more likely to involve its full complement of interconnected descending and
      ascending connections.

PMID- 1377979
TI  - Prostate cancer screening: current trends and future implications.
AB  - Screening for prostate cancer represents a clinical dilemma with no clear
      evidence to suggest decreased mortality from any diagnostic test. We now possess
      new knowledge regarding optimal combinations of DRE, TRUS, and PSA. While DRE and
      TRUS may be too subjective and PSA too nonspecific, their combined predictive
      values identify not only men at high risk but also those for whom continued
      frequent screening may not be cost effective. A monoclonal PSA decision level of
      no more than 4.0 ng/ml should be used, since 40 percent of cancers detected from
      4.0 to 10.0 ng/ml already have extracapsular extension. Assuming that DRE is
      performed by experienced examiners, the combination of PSA and DRE should produce
      cost-effective early detection and minimize missed cancers below 4.0 ng/ml. TRUS
      should be reserved for those patients with either PSA elevations and/or DRE
      abnormalities. The use of TRUS gland volume data to further modify PSA decision
      levels, such as the "predicted" PSA concept, may also improve TRUS biopsy
      criteria and predictive values. Prostate cancer detection can then be objectively
      limited to a small percentage of the population and better selected for earlier,
      more localized disease. The ultimate decrease in mortality from screening remains
      to be demonstrated in randomized trials or observed only after decades of
      increased public awareness about prompt early detection combined with effective,
      definitive therapy.

PMID- 1377980
TI  - Canadian MDs begin major push to promote early detection of prostate cancer.

PMID- 1377981
TI  - An intracellular calcium store regulates protein synthesis in HeLa cells, but it
      is not the hormone-sensitive store.
AB  - There is considerable evidence, reviewed by Brostrom and Brostrom [1], that Ca2+
      stores are involved in the regulation of protein synthesis. We provide evidence
      in HeLa cells that is consistent with their findings that depletion of Ca2+
      stores and not changes in cytosolic free Ca2+ ([Ca2+]i) inhibit protein
      synthesis, but we also show that the mechanism leading to depletion is critical.
      Specifically, depletion of stores by the Ca(2+)-mobilizing hormone histamine does
      not inhibit protein synthesis. In assessing the role of Ca2+ stores in protein
      synthesis, experiments in certain cell types have been complicated by the use of
      Ca2+ ionophores, which simultaneously elevate [Ca2+]i and deplete Ca2+ stores. We
      have measured total cell Ca2+, [Ca2+]i and protein synthesis in HeLa cells under
      conditions that allowed evaluation of the separate contributions of stores and
      [Ca2+]i. Using 1,2-bis(2-aminophenoxyethane)-N,N,N'N'-tetraacetic acid (BAPTA) as
      an intracellular Ca2+, chelator and thapsigargin, which inhibits the membrane
      Ca(2+)-ATPase of storage vesicles, total cell Ca2+ can be depleted and this
      depletion is enhanced by extracellular EGTA which blocks Ca2+ influx; [Ca2+]i is
      actually lowered by BAPTA under these conditions. Protein synthesis is inhibited
      by BAPTA in the presence of EGTA and by thapsigargin with or without EGTA.
      However, histamine which with EGTA, affects an equal degree of Ca2+ depletion
      does not inhibit protein synthesis. Thus, it is suggested that Ca2+ stores are
      not homogeneous, and that the hormone-sensitive store specifically does not play
      a role in the regulation of protein synthesis. In this respect, the hormone
      sensitive and insensitive stores do not functionally communicate and may be
      separately regulated.

PMID- 1377982
TI  - Evidence against a mitochondrial location of the 7-2/MRP RNA in mammalian cells.

PMID- 1377983
TI  - The essentials of DNA methylation.

PMID- 1377984
TI  - Low cost, computer-generated 35mm color slides.

PMID- 1377985
TI  - The human thymic dendritic cell phenotype and its modification in culture.
AB  - In order to extend our study of human thymic dendritic cells (DC) we have
      purified DC by density gradient separation followed by treatment with CD1 and CD2
      mAb and antibody-coated immunobeads. The resulting population contains 60 to 75%
      brightly HLA-DR+ cells. Morphological and functional studies demonstrate that
      these cells share the common characteristics of dendritic cells. Extensive
      phenotypic analysis of the purified DC has been made using a panel of mAb.
      Cytofluorometric assays with mAb reactive with common leucocyte antigen confirm
      that the brightly HLA-DR+ cells are of mesenchymal origin. Thymic DC express HLA
      DQ and HLA-class I antigens. They are also positive for the expression of CD45RA
      molecules and some express the ICAM-1 and the LFA-1 molecules. DC do not stain
      with a wide variety of anti-T, -B, and -monocyte or -M phi mAb and lack Fc gamma
      RIII, CR2, and CR3. Freshly isolated DC failed to stain with OKT6 mAb; however,
      they progressively acquire the CD1 molecule after a few days culture. The
      acquisition of CD1 molecule is selective since CD4, CD2, and HLA-ABC molecules
      are not upregulated under the same conditions. From phenotypic results, it was
      therefore possible to sort brightly HLA-DR+ or -DQ+ cells and so obtain greater
      than 90 to 95% purified human thymic DC. Such homogeneous DC populations are
      obviously of great interest for the study of thymic DC functions.

PMID- 1377986
TI  - An inducer of NKCF (NK cytotoxic factor) release: localization on target-cell
      membrane and initial characterization.
AB  - Natural killer (NK) cells are probably involved in the elimination of virus
      infected cells and of certain tumor cells. NK cell-mediated cytotoxicity (NK-CMC)
      was extensively studied and was found to consist of several steps. Following
      recognition and conjugation between the effector and the target cell, the latter
      one induces release of NK cytotoxic factor (NKCF) from the effector cells. The
      NKCF binds to the target cell which is subsequently killed. None of the molecules
      involved in these steps was completely characterized. In the present study it is
      demonstrated that isolated membranes of target cells can effectively induce the
      release of NKCF. Furthermore, the activity of such isolated membranes was found
      to be modulated by interferon (IFN) treatment of the cells prior to membrane
      isolation. It was therefore concluded that an NKCF-inducing structure (NKIS) is
      present on plasma membranes and is distinct from the NK-recognition structure.
      Similarly, the sensitivity to NK-CMC could be transferred from sensitive cells to
      IFN-gamma-treated (NK-resistant) cells by membrane fusion with the aid of Sendai
      virus envelope glycoproteins. It is proposed that transfer of NKIS is responsible
      for the acquired sensitivity to NK-CMC. In addition, it is shown that NKIS
      activity was recovered following membrane solubilization and reconstitution. Its
      level on cell surface was modulated by treatment of cells with tunicamycin, thus
      indicating that NKIS was probably a cell surface glycoprotein.

PMID- 1377987
TI  - The p21ras protein as an intermediate signaling molecule in the IL-4-induced HLA
      DR expression on normal and leukemic human myeloid cells.
AB  - We have previously demonstrated that the low number of interleukin-4 receptors
      (IL-4Rc) on HL-60 leukemia cells render this population susceptible to
      differentiation by IL-4. As it occurs with normal human monocytes, IL-4 induces
      the expression of HLA-DR surface antigens on HL-60 cells as well. The second
      messenger pathway(s) involved after the IL-4 stimulation leading to class II up
      regulation has not been fully examined. Here we show that IL-4-induced class II
      antigen expression on the HL-60 cell line or normal human monocytes is
      calcium/calmodulin-independent since theophylline (TPH, a calmodulin inhibitor)
      does not block the IL-4 effect. In addition, the pyruvate kinase C (PKC) pathway
      does not seem to participate in the process either because in our system
      activation of PKC by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) is
      insufficient by itself to induce HLA-DR. We found, however, that a second
      messenger pathway can be mediated by a G protein system since IL-4 concomitantly
      induces class II and p21ras expression which can be successfully blocked by a
      highly specific anti-p21ras monoclonal antibody. In addition, using another
      p21ras inducer, the 5-azacytidine C (5-AzaC), we showed that this agent can also
      induce the expression of p21ras and class II, both of which can be inhibited by
      the same antibody. Thus, it appears that IL-4 selects the G protein system as a
      signaling pathway in order to exert its action for the induction of HLA-DR on
      human normal monocytes or M2 leukemia target cells. Since monocytes and
      macrophages participate in virtually all immune reactions, the regulation of
      class II induction is of obvious importance.

PMID- 1377989
TI  - Stimulation or tolerization of an anti-myelin basic protein T lymphocyte line
      with membrane fragments from antigen presenting cells.
AB  - We have investigated the abilities of a cell-free supernatant of splenocytes or
      thymocytes, which have been incubated with myelin basic protein (MBP), and of
      membranes prepared by lysing these cells, to stimulate proliferation of a Lewis
      rat anti-MBP T lymphocyte line in vitro. The supernatant fraction, obtained by
      low-speed centrifugation, is thought to contain shed membrane fragments bearing
      class II MHC protein (Ia) and processed antigen. Almost all of 67 preparations of
      supernatant fraction and about a third (26/70) of the membrane preparations
      stimulate proliferation of the line cells in the absence of other antigen
      presenting cells and antigen. Some membrane preparations bearing the synthetic
      peptide S69 (residues 69-89 of MBP), containing the immunodominant
      encephalitogenic determinant for the Lewis rat, instead of processed MBP could
      also stimulate proliferation. Those membrane preparations bearing either
      processed MBP or synthetic S69, which do not stimulate proliferation, induce a
      state of unresponsiveness in which the cells do not proliferate but produce
      inositol phosphate. Stimulation of proliferation and induction of
      unresponsiveness were both inhibited by anti-Ia antibody. Addition of cyclosporin
      A prevents induction of unresponsiveness. Addition of allogeneic splenocytes or
      the cell-free supernatant fraction of syngeneic or allogeneic splenocytes or
      thymocytes, prevents induction of unresponsiveness by providing a necessary
      costimulatory signal. Further fractionation of the cell-free supernatant by high
      speed ultracentrifugation showed that the costimulatory signal resided in a
      particulate fraction which sedimented and not in the supernatant. These results
      indicate that the encephalitogenic peptide can induce anergy in T cells when
      presented on class II MHC in the absence of the costimulatory signal. Tolerizing
      forms of the membrane preparations which lack the costimulatory signal may be
      useful for in vivo treatment of autoimmune response.

PMID- 1377988
TI  - The VLA-4/VCAM-1 molecules participate in gamma delta cell interaction with
      endothelial cells.
AB  - The accumulation of T lymphocytes at the site of chronic inflammation depends on
      a number of factors including adherence of T cells to vascular endothelial cells
      (EC) and endothelial permeability. We examined the effects of human gamma delta +
      T lymphocytes on the permeability of EC to macromolecules and characterized the
      cell surface molecules that are involved in these interactions. In this model,
      the flux of [125I]albumin was measured across the EC monolayer after a short-term
      culture with cloned gamma delta cells. Our results show that coculture of
      activated, but not resting, gamma delta cells with EC enhances endothelial
      permeability by a cytolytic process. Pretreating gamma delta cells with
      monoclonal antibodies directed at either LFA-1 or VLA-4 molecules or pretreating
      EC with monoclonal antibodies directed against either ICAM-1 or VCAM-1 molecules
      significantly inhibited gamma delta cell-mediated enhancement in endothelial
      permeability. This indicated that VLA-4/VCAM-1 and LFA-1/ICAM-1 adhesion pathways
      participate in gamma delta cell-EC interaction.

PMID- 1377990
TI  - Human anti-pneumococcal polysaccharide antibodies are secreted by the CD5- B cell
      lineage.
AB  - To determine whether human antibody responses to T cell-independent pneumococcal
      polysaccharide antigens are derived from CD5+ or CD5- B cells, we utilized an
      ELISPOT assay to detect individual anti-polysaccharide antibody-secreting cells.
      Human anti-type IV pneumococcal polysaccharide antibody-secreting cells were
      found in the CD5- B cell subpopulation. An EBV transformed anti-pneumococcal
      antibody-secreting B cell line was also CD5-. The ontogeny of CD5 expressing B
      cells correlated with the age at which polysaccharide responsiveness is acquired
      (generally around age 2 years in humans). The CD5- B cell subset represents only
      25-30% of the B cells in young children, but this fraction increases throughout
      childhood to a plateau of 70-80% of the B cells in adults. These results support
      the hypothesis that the developmental change in responsiveness to T cell
      independent polysaccharide antigens in humans is associated with maturation of
      the CD5- B cell subset.

PMID- 1377991
TI  - CD16 on human gamma delta T lymphocytes: expression, function, and specificity
      for mouse IgG isotypes.
AB  - We examined the expression, the signal transduction capacity and mouse IgG
      isotype specificity of CD16 on human gamma delta T cells. CD16 is expressed by
      the majority of gamma delta T cells in peripheral blood and by part of the gamma
      delta T cell clones. The amount of CD16 expressed on gamma delta T cell clones
      varied considerably with passaging of the cells, but was always significantly
      less than on freshly isolated gamma delta T cells. Like CD16 on CD3- CD16+
      natural killer (NK) cells, CD16 on gamma delta T cells can act as an activation
      site triggering cytotoxic activity. CD16+ gamma delta T cell clones exerted
      antibody-dependent cellular cytotoxicity (ADCC) which could be blocked by anti
      CD16 mAb. ADCC activity of gamma delta T cell clones was also inhibited by anti
      CD3 mAb, suggesting a functional linkage between the CD16 and CD3 activation
      pathways. MAb directed against CD16 induced lysis of Fc gamma R+ target cells by
      CD16+ gamma delta T cell clones. The mouse IgG-isotype specificity of CD16 on
      gamma delta T cells was analyzed using isotype switch variants of a murine anti
      glycophorin A mAb in EA rosette assays, and was found to be identical to that of
      CD16 on CD3- CD16+ NK cells, i.e., highest affinity for mIgG2a, intermediate
      affinity for mIgG2b, and undetectable binding of mIgG1-sensitized erythrocytes.
      CD16 was partly modulated from the cell surface of both gamma delta T cells and
      NK cells after rosette formation with mIgG2a-sensitized erythrocytes, indicating
      that the rosette formation was indeed mediated via the CD16 molecule.

PMID- 1377992
TI  - Splanchnic and total body oxygen consumption in experimental fecal peritonitis in
      pigs: effects of dextran and iloprost.
AB  - Tissue oxygenation in the gastrointestinal tract and in the liver was studied in
      a porcine model where septic shock was induced by fecal peritonitis. The effects
      of different fluid regimes were compared. In one group (n = 8) a moderate amount
      of crystalloid fluids was given, in another (n = 7) crystalloids and colloids,
      and in a third group (n = 6) iloprost, a prostacyclin analogue, was administered
      intra-arterially (10 ng x kg-1 b.w. x min-1) in combination with the crystalline
      and colloid fluid regime. Septic shock induced by fecal peritonitis reduced
      cardiac index and oxygen supply to splanchnic organs. Iloprost improved the
      hepatic arterial blood flow, and tended to attenuate the reduction in liver
      oxygen delivery. Oxygen consumption (VO2) in the gastrointestinal tract and the
      liver was significantly increased in the group given crystalloids. These animals
      developed a hypovolemic/hypodynamic septic shock. Liver VO2 in these animals
      became flow dependent reflected by increasing hepatic venous lactate values and
      inversion of lactate turnover by the liver. In the two other groups
      gastrointestinal and liver VO2 remained constant during the observation period.
      Oxygen extraction over the liver increased when oxygen delivery decreased. The
      increased liver VO2 is suggested to be secondary to impaired microcirculation and
      accumulation of macrophages and leukocytes in the septic liver.

PMID- 1377993
TI  - A rapid separation of alpha- and beta-lipoproteins by affinity chromatography.
AB  - A rapid and inexpensive separation of alpha- and beta-lipoproteins has been
      achieved using sulfated dextran beads as an affinity chromatography medium. The
      separation is completed in less than 15 min and the cholesterol content of the
      lipoprotein fractions can then be determined in a separate procedure.

PMID- 1377994
TI  - Laboratory monitoring of androgenic activity in benign prostate hypertrophy
      treated with a 5 alpha-reductase inhibitor.
AB  - Testosterone and androstenedione are metabolized by 5 alpha- and 5 beta
      reductases to androsterone (A) and etiocholanolone (E), respectively. These are
      excreted in the urine as conjugates, and the A/E ratio in normal men is usually
      greater than or equal to 1.5 (as opposed to 1 in women) because of the high 5
      alpha-reductase activity in the prostate. The A/E ratio can be determined simply
      by gas chromatography after acid hydrolysis of a urine sample, extraction of
      steroids, and formation of trimethylsilyl derivatives. A timed collection of
      urine is unnecessary because the ratio of A/E is used rather than absolute
      values. In men suffering from benign prostate hypertrophy who are treated with
      Finasteride (a 5 alpha-reductase inhibitor), the A/E ratio decreases to less than
      0.5. The A/E ratio decrease can be detected long before there is clinical
      improvement.

PMID- 1377995
TI  - Radioreceptor assay for quantifying FK-506 immunosuppressant in whole blood.
AB  - We describe a quantitative radioreceptor assay (RRA) for quantifying FK-506 in
      whole blood. FK-506 extracted from whole blood with a cyclohexyl-sorbent column
      competes with [3H]dihydro-FK-506 for binding to a partially purified preparation
      of FK-506 binding protein (FK-BP). Free and protein-bound FK-506 are separated on
      LH 20 Sephadex chromatographic columns. We compared the results of this method
      with those of an enzyme immunoassay that uses a monoclonal antibody: r = 0.97,
      Sy/x = 0.039. Between-day precisions (CV) at FK-506 concentrations of 8 and 17
      micrograms/L were 9.2% and 8.2%, respectively. Within-run precisions were 5.9%,
      8.1%, and 9.4%, respectively, at 4, 8, and 15 micrograms/L. Analytical recovery,
      evaluated at 5, 10, 15, 20, and 25 micrograms/L for FK-506 added to whole blood,
      ranged from 98% to 103%. The assay can reliably quantify FK-506 blood
      concentrations between 1.0 and 25 micrograms/L.

PMID- 1377996
TI  - Sensory nerves in the airways as a target for drug development.
AB  - 1. Electrical stimulation (2.5-10 Hz, 80 V, 1 ms for 15 s) within the spinal
      canal of the pithed guinea-pig pretreated with atropine, D-tubocurarine and
      pentolinium caused a bronchoconstrictor response, indicated by a rise of
      insufflation pressure. 2. The magnitude of these non-cholinergic neuronal
      bronchoconstrictor responses were frequency-dependent, capsaicin-sensitive and
      temperature-dependent. 3. Responses could be inhibited by the alpha 2
      adrenoceptor agonist B-HT920 (3 mg/kg, i.v.) and the mu-opioid agonist H-Tyr-D
      Arg-Phe-Lys-NH2 (DALDA; 1 mg/kg, i.v.) and the attenuation observed could be
      overcome by use of the respective antagonists idazoxan (3 mg/kg, i.v.) and
      naloxone (3 mg/kg, i.v.). 4. Substance P-induced bronchoconstriction (0.3
      micrograms/kg, i.v.), but not that due to electrical stimulation, was attenuated
      by indomethacin (3 mg/kg, i.v.), indicating an indirect action of substance P via
      a product of arachidonic acid metabolism. 5. The prostanoid product of the
      substance P response was probably thromboxane A2. 6. Hence, novel drug
      development could be directed towards tachykinin receptors or to the synthesis,
      release and degradation of neuropeptides.

PMID- 1377997
TI  - Allotype-dependent stimulation of peripheral blood and synovial lymphocytes by
      IgG3 in rheumatoid arthritis.
AB  - The immunopathologic process of rheumatoid arthritis (RA) is primarily expressed
      in the synovium where rheumatoid factor (RF) synthesis is concentrated. We
      hypothesized that RF synthesized by rheumatoid synovial cells (RSC) may be driven
      via a T cell-mediated immune response developed against IgG3 epitopes. To
      identify and characterize specific RSC RF epitopes and T cell antigens, two 28
      amino acid peptides homologous with the C-terminus of IgG1 (P1) and IgG3 [G3m(5)]
      (P3) were synthesized and used in RF-binding studies and lymphocyte proliferation
      assays. Our results indicate that (i) the C-terminus of the CH3 domain contains
      epitopes for IgG3-reactive RSC RF; (ii) IgG3-reactive RSC RF binds primarily to
      IgG3 [G3m(5)]; (iii) P3 stimulated proliferation of T lymphocytes from both RA
      peripheral blood and RSC; and (iv) RF production was enhanced by P3 in selected
      RA cell cultures. These observations suggest that the C-terminus of IgG3 allotype
      G3m(5) may be important in T cell activation and RF production in RA.

PMID- 1377998
TI  - Hepatic glutamine metabolism in the septic rat.
AB  - 1. The hepatic metabolism of glutamine, alanine, ammonia, urea, glutathione and
      glucose was studied in rats made septic by caecal ligation and puncture and was
      compared with that in rats that had undergone sham operation (laparotomy). 2.
      Sepsis resulted in increases in the plasma activities of gamma
      glutamyltransferase (P less than 0.001), alanine aminotransferase (P less than
      0.001) and aspartate aminotransferase (P less than 0.001), the serum total and
      direct bilirubin concentrations (P less than 0.001), and the blood lactate (P
      less than 0.01), glutamine (P less than 0.05), alanine (P less than 0.001) and
      urea (P less than 0.05) concentrations, but produced decreases in the blood
      ketone body (P less than 0.001) and glutathione (P less than 0.05) concentrations
      and in the plasma cholesterol concentration (P less than 0.05). These changes
      were associated with marked negative nitrogen balance in septic rats. 3. Sepsis
      increased total hepatic blood flow (by 22.7%) together with hepatic arterial flow
      (by 25.8%) and portal venous flow (by 18.7%). Sepsis resulted in marked increases
      in the net rates of hepatic extraction of glutamine (by 164%), alanine (by 138%)
      and ammonia (by 259%) with concomitant increases in the net rates of hepatic
      release of glutamate (by 105%), glutathione (by 87.5%), glucose (by 70.1%) and
      urea (by 100.4%). 4. Sepsis increased the activities of liver carbamoylphosphate
      synthase (by 16.4%), ornithine transcarbamylase (by 29.8%), argininosuccinate
      synthase (by 28.1%) and arginase (by 33.8%). 5. Septic rats exhibited marked
      increases in hepatic protein (by 46.0%), RNA (by 43.4%) and DNA (by 37.7%)
      contents. These changes were accompanied by marked increases in the activity of
      thymidine kinase (by 35.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1377999
TI  - The relationship between human long-latency somatosensory evoked potentials
      recorded from the cortical surface and from the scalp.
AB  - In scalp recordings, stimulation of the median nerve evokes a number of long
      latency (40-300 msec) somatosensory evoked potentials (SEPs) whose neural origins
      are unknown. We attempted to infer the generators of these potentials by
      comparing them with SEPs recorded from the cortical surface or from within the
      brain. SEPs recorded from contralateral sensorimotor cortex can be characterized
      as "precentral," "postcentral," or "pericentral." The scalp-recorded P45, N60 and
      P100 potentials appear to correspond to the pericentral P50, N90 and P190
      potentials and are probably generated mainly in contralateral area 1 of
      somatosensory cortex. The scalp-recorded N70-P70 appear to correspond to the
      precentral and postcentral N80-P80 and are generated mainly in contralateral area
      3b of somatosensory cortex. The scalp-recorded N120-P120 appear to correspond to
      the intracranial N100-P100 and are probably generated bilaterally in the second
      somatosensory areas. N140 and P190 (the "vertex potentials") are probably
      generated bilaterally in the frontal lobes, including orbito-frontal, lateral and
      mesial (supplementary motor area) cortex. The supplementary sensory area probably
      generates long-latency SEPs, but preliminary recordings have yet to confirm this
      assumption. Most of the proposed correspondences are speculative because the
      different conditions under which scalp and intracranial recordings are obtained
      make comparison difficult. Human recordings using chronically implanted cortical
      surface electrodes, and monkey studies of SEPs which appear to be analogs of the
      human potentials, should provide better answers regarding the precise generators
      of human long-latency SEPs.

PMID- 1378000
TI  - Intraoperative spinal cord monitoring during surgery for aortic aneurysm:
      application of spinal cord evoked potential.
AB  - Spinal cord evoked potentials elicited by direct stimulation of the spinal cord
      were monitored in 21 patients during thoracic or thoraco-abdominal aortic
      aneurysm surgery. Flexible catheter-type electrodes were used for both
      stimulating and recording. The basic pattern of the spinal cord evoked potential
      consisted of an initial spike and a subsequent polyphasic component. The earliest
      and most frequent alterations after cross-clamping of the aorta were changes in
      the configuration or amplitude of the polyphasic component. In 13 patients who
      exhibited no change except minor alterations of the polyphasic component during
      the initial test clamping for 15 or 20 min, subsequent graft replacements were
      safely performed without reimplantation of intercostal vessels. In 2 patients who
      had sudden cardiac arrests, the evoked potential completely disappeared. The
      polyphasic component disappeared first, followed by the initial spike. Another
      patient developed acute loss of the potential after the aneurysm was incised,
      presumably due to distal aortic hypoperfusion. In this case, prolonged distal
      hypotension resulted in flaccid paraplegia. Intraoperative monitoring of the
      spinal cord evoked potential is a useful method for the early detection of spinal
      cord ischemia during surgery requiring aortic occlusion.

PMID- 1378001
TI  - Pyramidal tract function during onset of brain death.
AB  - In 51 patients with primary brain lesions, who fulfilled the criteria of brain
      death, sequential recording of transcranial magnetic evoked potentials (TMEPs)
      and somatosensory evoked potentials (SEPs) were performed. In all comatose
      patients with apnoeic cranial nerve areflexia the TMEP could not be elicited,
      while the response after cervical magnetic stimulation was always preserved.
      Similarly, no cortical SEPs were preserved in apnoeic cranial nerve areflexia;
      however, the cervical somatosensory response was preserved in 44%. In
      deteriorating patients with coma grade III TMEPs were preserved in 3 instances,
      while cortical SEPs were already absent. Current brain death criteria, however,
      were not challenged, as TMEPs were absent in all 51 patients, at the latest when
      apnoea was noted.

PMID- 1378003
TI  - Event-related EEG potentials in mild dementia of the Alzheimer type.
AB  - Most studies on event-related EEG potentials in dementia have focussed on the P3
      component and used auditory stimuli only. In the present study, N2b was analysed
      in the usual auditory oddball task in addition to P3, and a visual task was
      employed ("Push"/"Wait"), with recordings including an occipital scalp site.
      Seven Alzheimer-type patients, with their mean IQ still in the normal range, were
      compared to age-matched normal controls. In the oddball task, P3 did not differ
      between groups but the patients' N2b was delayed. The main difference in the
      Push/Wait task was in an occipital P270, which component was distinctly larger in
      the patients. It is suggested that both differences reflect the disintegration of
      patients' cognition: stimuli are perceived in a normal way but then a gap arises
      due to uncertainty what to do with the perceived event.

PMID- 1378002
TI  - Serial visual evoked potential recordings in geriatric psychiatry.
AB  - Serial visual evoked potentials to flash and pattern reversal stimuli were
      recorded in elderly patients with senile dementia of the Alzheimer type (SDAT),
      multi-infarct dementia (MID) and functional psychiatric illness, and in a group
      of elderly control subjects. Recordings were made at 6 monthly intervals over a 2
      year period. Latency and amplitude of the main components were measured and the
      flash P2-pattern reversal P100 latency difference value was calculated. In all
      groups significant changes over time did not occur for any parameters but in the
      SDAT group the regression coefficient for the latency of the flash P2 component
      and the flash P2-pattern reversal P100 latency difference was significant,
      reflecting a trend towards increasing flash P2 latency as time progressed. The
      flash P2-pattern reversal P100 latency difference was longer in the SDAT and MID
      groups than in the functional patients, confirming the findings of previous
      reports. The latency difference in the SDAT group only was significantly greater
      than that in the control group.

PMID- 1378004
TI  - Wave form variations in auditory event-related potentials evoked by a memory
      scanning task and their relationship with tests of intellectual function.
AB  - The inter-subject wave form variability of auditory event-related potentials
      (ERPs) evoked by digit probe identification in a memory-scanning task (Sternberg
      paradigm) and the effects of reaction time (RT) and task difficulty were studied
      in 26 healthy subjects. The response wave forms were compared with the
      performance of psychological tests of intelligence and memory. ERPs to 1-digit
      sets consisted of a sequence of waves identified as P100, N170, P250, N290, P400,
      P560 and N640. The major inter-subject difference in the response wave form was
      either the presence or absence of the late parietal positive wave P560. This wave
      occurred significantly more often in responses associated with larger memory sets
      and slow RT, suggesting that its presence reflects subjective difficulty in
      performing a task. With increasing set size, the P400 showed variable effects in
      different subjects, ranging from relative preservation of amplitude, through
      attenuation, to replacement or overlap by a broad surface-negative wave. This
      predominantly 'negative-going' effect of increasing task difficulty on the P400
      was significantly correlated with scores of psychological tests; the greater the
      amplitude difference between the responses to easy and more difficult tasks, the
      better the scores, suggesting that these wave form changes reflect a more
      effective cognitive processing mechanism.

PMID- 1378006
TI  - Binaural stimulation reveals functional differences between midline and temporal
      components of the middle latency response in guinea pigs.
AB  - Two morphologically distinct auditory middle latency response (MLR) wave forms
      can be recorded from the surface of the guinea pig brain. The temporal response
      is recorded from the temporal lobe contralateral to the stimulus ear, and the
      midline response is recorded over the posterior midline. Experimental evidence
      suggests that different neural generators contribute to the two responses.
      Furthermore, it appears that the temporal response principally reflects activity
      of the primary auditory pathway while the midline response reflects non-primary
      pathways. Although it is known that neurons throughout the auditory pathway
      exhibit distinct binaural interaction (BI) properties, thus far there have been
      no systematic attempts to differentiate the MLR wave forms in response to
      binaural stimulation. The purpose of this study was to determine if binaural
      click stimulation could functionally differentiate the midline and temporal MLR
      responses in the guinea pig. Binaural click stimulation caused a significant
      decrease in temporal MLR peak amplitudes, and a significant increase in midline
      MLR amplitudes. The fact that different BI patterns were observed suggests that
      the two MLR components are functionally distinct. The data further support the
      hypothesis that the midline and temporal MLR in guinea pigs reflect different
      neural generators and pathways.

PMID- 1378005
TI  - Area-specific self-regulation of slow cortical potentials on the sagittal midline
      and its effects on behavior.
AB  - Exteroceptive feedback was given for negative and positive shifts in slow
      potentials (SPs) recorded from Fz, Cz, or Pz (between groups design). Slow
      potentials at the feedback site were referred to adjacent scalp and non-cephalic
      electrodes, so as to confine SP shifts to the feedback location. Area-specific
      regulation of SPs was obtained at each midsagittal site after 3 days of feedback
      training. Subjects reported sensorimotor and emotional arousal when negative SP
      shifts were trained frontally, but not when negative shifts were trained
      parietally (cognitive/attentional strategies reported after parietal feedback).
      Area-specific regulation of SPs was subsequently abolished when behavioral tasks
      were added to further probe frontal/parietal differences (dual-task procedure).
      These findings indicate that area-specific self-regulation of SPs is possible on
      the sagittal midline, and that self-regulated parietal SPs (in contrast to
      frontal ones) arise from non-motoric generators. The source of SP self-regulation
      was more readily probed by verbal reports of feedback strategy than by study of
      dual-task relations, because feedback control was disrupted by the dual-task
      requirement.

PMID- 1378007
TI  - Event-related neuronal responses in the human strio-pallido-thalamic system. I.
      Sensory and motor functions.
AB  - Multiunit activity was recorded from strio-pallido-thalamic sites in parkinsonian
      patients bearing gold electrodes for diagnosis and therapy. The patients
      voluntarily participated in tasks designed to study neuronal correlates of both
      physical and semantic characteristics of stimuli as well as motor responses. Six
      modifications of the stimulus-response paradigm were used: visual odd-ball,
      visual and acoustic odd-ball tasks; tasks in which either the stimulus intensity
      or the meaning of non-target stimuli varied; single-stage delayed response and
      dual-stage delayed response tasks, respectively. In each task the patients had to
      evaluate some of the stimulus characteristics and to respond in a particular way
      according to the preliminary instructions. Peristimulus time histograms for each
      multiunit separately as well as profiles of reactions and profiles of reaction
      differences for the whole set of multiunits were calculated and subjected to
      statistical analysis. Two functional groups of subcortical neuronal reactions,
      stimulus-related and response-related activities, were separated. The stimulus
      related activities of most multiunits were modality-unspecific. Their most
      striking feature was dependence on stimulus relevance and also its probability,
      the strongest reactions observed in response to task relevant stimuli occurring
      with low probability. The response-related activities occurred prior to
      initiation of movements, dependent upon the particular action and its
      probability. The data suggest at least two different and spatially overlapping
      subcortical channels responsible for goal-directed behaviour: the one related to
      stimulus assessment and the other to preparation for motor action.

PMID- 1378008
TI  - Event-related neuronal responses in the human strio-pallido-thalamic system. II.
      Cognitive functions.
AB  - Multiunit activity was recorded from the strio-pallido-thalamic system in the
      same parkinsonian patients (as described in the previous paper) who bore gold
      electrodes for diagnosis and therapy. The patients voluntarily participated in
      various tasks designed to study neuronal correlates of cognitive functions: "odd
      omissions," "short-term memory," "cued bimodal," "assessment," and "dual-stage
      delayed response" tasks. Preparatory-related activities were found in multiunits
      reacting to sensory cues. In a few multiunits these activities depended upon the
      specific features of the stimuli that were anticipated for evaluation. The most
      striking characteristic of stimulus-related activity was the suppression of the
      multiunit responses when the stimuli become behaviourally meaningless. The
      hypothesis of action programming is discussed: the loop, including the cortex,
      neostriatum, pallidum and appropriate parts of the thalamus, is involved in the
      selection of actions, thus providing the organization of sequential behaviour.

PMID- 1378009
TI  - Improving the reliability of pattern electroretinogram recording.
AB  - The pattern electroretinogram (PERG) is a small electrical response of the retina
      to a reversing checkerboard pattern, usually less than 6 microV in amplitude.
      Unfortunately, the PERG can be obscured by artifacts such as blinks, eye
      movements, poor fixation, and amplifier saturation. Amplitude criterion artifact
      rejection systems found on commercial signal averagers eliminate large amplitude
      artifacts but are insensitive to small amplitude artifacts associated with
      amplifier saturation. Such saturation often occurs for several recording sweeps
      after large amplitude signals such as eye blinks are rejected. The presence of
      post-saturation artifacts complicates clinical PERG analysis. In this paper we
      describe procedures to remove these small amplitude artifacts from the PERG.
      These include computer selection of inputs for averaging and use of tracings with
      small input numbers to approximate PERG amplitudes. These procedures greatly
      reduce the variability of PERG amplitudes in the normal population, making PERG
      amplitude a more reliable clinical measure.

PMID- 1378010
TI  - Ventricular premature beats in young subjects without evidence of cardiac
      disease: histological findings.
AB  - This report describes the results of right ventricle endomyocardial biopsies from
      26 subjects (mean age 27 +/- 10 years) with premature ventricular beats and
      normal cardiac anatomy and mechanical function. Light microscopy examination
      revealed normal myocardium in 10 subjects (38%), acute myocarditis in two (7%),
      borderline myocarditis in one (3.5%), non-specific histological abnormalities
      including cellular hypertrophy, fibrosis and degenerative changes in 11 (42%),
      vasculitis in one (3.5%) and findings compatible with right ventricular dysplasia
      in the final subject (3.5%). The frequency of ventricular premature beats, as
      assessed by Holter monitoring, and the results of electrophysiological testing
      did not correlate with histopathological findings and their severity. These data
      indicate that some young subjects with premature ventricular beats of unknown
      origin have abnormal right ventricular biopsy findings. Adequate follow-up will
      probably demonstrate the clinical utility of these observations.

PMID- 1378011
TI  - Determinants of left ventricular filling dynamics: alteration in the Doppler
      derived transmitral filling profile with progressive impairment of cardiac
      function in a dog preparation.
AB  - To clarify the factors determining transmitral filling, left ventricular and
      atrial pressures (LVP and LAP) and Doppler-derived diastolic indices were
      analysed in six anaesthetized dogs at various right atrial pacing rates during
      dextran infusion. The relationship of the late to early diastolic peak velocity
      ratio (A/E ratio) to end-diastolic LVP (LVEDP) showed a quadratic curve concave
      to the LVEDP axis in five animals (r2 = 0.320-0.588). An elevation in LVEDP up to
      25 mmHg accompanied an increase in A/E ratio (ascending limb), and further LVEDP
      elevation caused its inverse decline (descending limb). Multiple regression
      analysis indicated that A/E ratio correlated positively with maximal LVP, a-wave
      LAP and heart rate, and negatively with v-wave LAP in both limbs. The time
      constant of isovolumic LVP decline, which was prolonged as LVEDP was elevated,
      was a positive correlate of A/E ratio in the ascending limb, but lost its
      influence on A/E ratio in the descending limb. An elevation in v-wave LAP must
      have masked the expected effect of left ventricular relaxation abnormality on A/E
      ratio in this limb. Thus, the transmitral filling profile did not alter
      unidirectionally, but returned to that seen before volume loading, with a
      simultaneous progressive impairment of cardiac function.

PMID- 1378012
TI  - Anergy induced by thymic medullary epithelium.
AB  - Thymocytes can be rendered tolerant by non-deletional mechanisms upon interaction
      with major histocompatibility complex (MHC) antigens on thymic epithelium.
      Whether the epithelial cells in the cortex or medulla could mediate this effect
      was not clear so far. To address this question, a transgenic mouse was generated
      in which the bovine keratin IV promoter was used to control expression of the
      alloantigen Kb. In the periphery the Kb transgene was expressed on a subset of
      keratinocytes. In the thymus expression was restricted to a subpopulation of
      medullary epithelial cells. No expression was found in the cortex. Such a tissue
      distribution has been reported for the keratin IV molecule demonstrating the
      faithfulness of the promoter used here. To follow the fate of the Kb-reactive
      thymocytes, this mouse was mated with another transgenic mouse expressing an anti
      Kb T cell receptor (TcR). In the double-transgenic mice the CD8+CD4- thymocytes
      were not deleted but they were found to be anergic as assayed by their failure to
      be activated in vitro by either Kb-positive spleen cells or by cross-linked anti
      TcR antibodies. These observations establish that expression of an MHC class I
      antigen in the thymic medullary epithelium is sufficient to induce anergy in the
      mature CD8+CD4- thymocyte population.

PMID- 1378013
TI  - Characterization and measurement of CD5+ B cells in normal and Trypanosoma
      congolense-infected cattle.
AB  - CD5+ B cells in cattle are present in peripheral blood and spleen, but not in
      lymph nodes, tonsils or Peyer's patches. Compared to classical B cells, they
      express similar levels of B cell surface markers, but have higher levels of
      surface IgM. We failed to find evidence for IgD on bovine B lymphocytes. The CD5+
      B cells expressed CD11b (Mac-1). Another small subpopulation of B cells carried
      CD11b but not CD5. In cattle infected with Trypanosoma congolense, a dramatic
      increase in the percentage of CD5+ B cells in blood and spleen was observed. This
      increase occurred 7-10 days after parasites were first detected in the blood and
      correlated with the increase in serum IgM and the increase in the absolute number
      of B cells that is typical to trypanosome-infected animals. The increase in B
      cells was found to be due mainly to the expansion of the CD5+ B cell
      subpopulation. The cause of the amplification of the CD5+ B cells and their
      possible involvement in the production of autoantibodies and non-parasite
      specific antibodies which have been described in trypanosome-infected animals are
      discussed.

PMID- 1378014
TI  - Restoration of the LFA-3 adhesion pathway in Burkitt's lymphoma cells using an
      LFA-3 recombinant vaccinia virus: consequences for T cell recognition.
AB  - Conjugate formation between cytotoxic T lymphocytes (CTL) and target B cells, as
      observed in vitro, is mediated by interactions between adhesion molecules on the
      two cell surfaces rather than involving immune recognition through the T cell
      receptor. It is still not clear to what extent such adhesive contacts facilitate
      the process of immune recognition and target cell lysis. However, work on the
      Epstein-Barr virus (EBV)-associated malignancy Burkitt's lymphoma (BL) has
      suggested that down-regulation of one particular adhesion molecule, the
      lymphocyte function-associated antigen LFA-3, on the tumor cell surface is a key
      factor in allowing these target cells to escape EBV-specific T cell surveillance.
      To examine this directly, we used a cDNA for the full-length transmembrane form
      of LFA-3 to construct a recombinant vaccinia virus (Vacc-LFA 3), which is capable
      of restoring surface LFA-3 in adhesion molecule-negative BL cell lines to levels
      as high as seen in EBV-transformed lymphoblastoid cell lines (LCL); biochemical
      studies confirmed expression of the authentic N-glycosylated protein. The
      recombinant vaccinia-encoded LFA-3 was functional as an adhesion molecule since
      BL cells acutely infected with Vacc-LFA-3 then acquired the ability to form
      conjugates with activated T cells in vitro. However, there was no clear
      dependence upon LFA-3 when such BL cell lines were tested as targets for
      cytotoxic T lymphocytes (CTL). Firstly, LFA-3- BL cells could be killed by
      allospecific CTL recognizing HLA class I alloantigens, in some cases as
      efficiently as the corresponding LCL. In other cases where lysis was slightly
      below that of the LCL, Vacc-LFA-3 infection of the BL cells increased lysis up
      to, but never beyond, LCL values. Secondly, we studied the sensitivity of BL to
      EBV-specific HLA class I-restricted CTL using a BL target line which was LFA-3-
      but which expressed the same spectrum of EBV target proteins as an LCL. This line
      was not recognized by appropriately HLA-matched effectors, even after restoration
      of LFA-3 expression. We conclude that the LFA-3 status of BL cells influences
      their conjugate forming ability in in vitro assays but not necessarily their
      sensitivity to immune T cell-mediated cytolysis.

PMID- 1378015
TI  - Human monoclonal and polyclonal anti-human immunodeficiency virus-1 antibodies
      share a common clonotypic specificity.
AB  - Human monoclonal and purified polyclonal anti-human immunodeficiency virus (HIV)
      1 antibodies were tested for binding to a murine monoclonal anti-idiotypic
      antibody (1F7, IgM, kappa). Four human monoclonal anti-p24 and three human
      monoclonal anti-gp120 antibodies express the 1F7 clonotype, while one human
      monoclonal anti-gp41 antibody does not bind to 1F7. Affinity-purified anti-p24
      and anti-gp120 antibodies from HIV-1-infected individuals also react with 1F7.
      Western blot analysis and enzyme-linked immunosorbent assay confirmed that 1F7
      reacts with human antibodies of different HIV-1 antigen specificities. A survey
      of sera from 329 HIV-1-infected individuals showed binding to 1F7 in 239 sera
      (72.6%) while 1F7 was not reacting with 109 HIV-1-negative sera. These results
      show that 1F7 idiotype is an HIV-1 infection-associated clonotypic marker shared
      by anti-HIV-1 antibodies with different epitope specificites.

PMID- 1378016
TI  - CD4+ suppressor cells of autoimmune encephalomyelitis respond to T cell receptor
      associated determinants on effector cells by interleukin-4 secretion.
AB  - We have previously demonstrated that CD4+ suppressor T cells (Ts) inhibit the
      secretion of interferon (IFN)-gamma, but not interleukin (IL)-2, by effector
      cells of experimental autoimmune encephalomyelitis (EAE). Moreover, CD4+ Ts
      appear to regulate IFN-gamma by secretion of transforming growth factor-beta. We
      now show that CD4+ Ts produce a lymphokine with IL-4 activity in response to a
      determinant associated with EAE effector cells. CD4+ Ts do not proliferate or
      secrete IFN-gamma, IL-2, or IL-4 in response to myelin basic protein, nor do CD4+
      Ts proliferate or secrete IL-2 when co-cultured with irradiated EAE effector
      cells. Rather, CD4+ Ts secrete IL-4 when co-cultured with either irradiated
      effector spleen cells or irradiated encephalitogenic line cells. CD4+ Ts do not
      secrete IL-4 in response to OVA-primed spleen cells, suggesting that the
      suppressor cells recognize a determinant specific to encephalitogenic T cells.
      Furthermore, CD4+ Ts secrete IL-4 when cultured with synthetic T cell receptor
      (TcR) V beta 8, but not TcR V beta 14 peptide, in the presence of antigen
      presenting cells. This response is major histocompatibility complex class II
      restricted as demonstrated by inhibition of the response with anti-class II
      monoclonal antibody. These results suggest that CD4+ Ts recognize a determinant
      associated with TcR on the surface of EAE effector cells and respond by secreting
      IL-4, in a manner analogous to the Th2 lymphocyte subtype.

PMID- 1378017
TI  - GMP-140 (P-selectin/CD62) binds to chronically stimulated but not resting CD4+ T
      lymphocytes and regulates their production of proinflammatory cytokines.
AB  - GMP-140 (P-selectin), a 140-kDa granular membrane glycoprotein localized to the
      alpha granules of platelets and the Weibel-Palade bodies of endothelial cells, is
      thought to play an important role in adhesive interactions predominantly between
      granulocytes, platelets and vascular endothelial cells during inflammation.
      Although GMP-140 binds to granulocytes, its binding to lymphocytes has not been
      demonstrated. Using genetically engineered IgG C gamma 1 fusion protein of the
      extracellular domains of GMP-140, we demonstrate that GMP-140 binds to
      chronically antigen (Ag)-stimulated CD4+ T cells. Freshly isolated CD4+ T cells
      did not bind GMP-140, but priming and subsequent stimulation with alloantigen
      induced and gradually increased expression of GMP-140-reactive structures on
      their surface. T cells isolated from rheumatoid synovial fluids also exhibited
      strong binding to GMP-140. The binding of GMP-140 to primed T cells is not
      influenced by preactivation with phorbol 12-myristate 13-acetate, is almost
      completely abolished by pretreatment of T cells with neuraminidase or trypsin,
      and is also strongly inhibited by EDTA, the soluble sulfated glycans dextran
      sulfate, fucoidan, and heparin, but not by chondroitin sulfates. In spite of its
      strong binding to Ag-primed T cells, GMP-140 did not modulate the proliferative
      responses of these cells to various stimuli. However, GMP-140 in conjunction with
      anti-T cell receptor alpha beta monoclonal antibodies augmented the production of
      granulocyte-macrophage colony-stimulating factor GM-CSF and inhibited the
      production of interleukin-8 by Ag-primed T cells without influencing their tumor
      necrosis factor-alpha production. These results suggest that GMP-140 binds to
      chronically stimulated CD4+ T cells and differentially modulates their production
      of proinflammatory cytokines. The ability of Ag-primed T cells to bind GMP-140
      may facilitate interactions with activated platelets and endothelial cells
      affecting the course of inflammation.

PMID- 1378018
TI  - Cell adhesion molecules of the immunoglobulin supergene family as tissue-specific
      autoantigens: induction of experimental allergic neuritis (EAN) by P0 protein
      specific T cell lines.
AB  - The P0 glycoprotein is a homophilic cell adhesion molecule of the immunoglobulin
      supergene family which is responsible for maintaining the structure of compact
      internodal myelin in the peripheral nervous system (PNS). Utilizing a panel of
      synthetic P0 peptides two distinct T cell epitopes have been identified that can
      induce T cell-mediated experimental autoimmune neuritis (EAN) in the Lewis rat.
      One T cell epitope (amino acid residues 56-71), is located within the
      extracellular, immunoglobulin-like domain of P0, while the other disease-inducing
      T cell epitope (residues 180-199) is located within the proteins cytoplasmic
      carboxyterminal domain. The adoptive transfer of 10(6) CD4+ T line cells specific
      for either of these peptide antigens induced EAN in syngeneic recipients.
      However, while the pathogenic response induced by both peptide-specific T cell
      lines was identical, their epitopes differ markedly in their immunologic
      properties in vivo. In particular while the response to peptide p180-199 was
      immunodominant in animals immunized with either purified P0 protein or the native
      membrane-bound P0 protein in autologous rat peripheral nerve myelin, no response
      to peptide p56-71 was detected, indicating that this epitope is cryptic. This
      study provides the first experimental evidence that the immunoglobulin-like
      domains of members of the immunoglobulin supergene family can function as target
      autoantigens in T cell-mediated autoimmune disease.

PMID- 1378019
TI  - Identification of an immunodominant type-II collagen peptide recognized by T
      cells in H-2q mice: self tolerance at the level of determinant selection.
AB  - The T cell recognition of type-II collagen (CII) in H-2q mice, susceptible to CII
      induced arthritis, was analyzed. With the use of T cell hybridomas derived from
      rat CII-immunized mice, a peptide corresponding to amino acids 245-270 on chick
      CII was found to harbor a T cell epitope which is present on heterologous CII
      (chick, rat, human, and bovine CII) but not on autologous CII. It was shown that
      this epitope was located within amino acids 260-270, although flanking regions in
      either direction were necessary for proper recognition. A peptide corresponding
      to human CII (256-270) was used for further studies. A single amino acid
      difference at position 266 between mouse CII (aspartic acid) and heterologous CII
      (glutamic acid) strongly influenced recognition of this peptide. No response
      towards the mouse peptide was seen with any of the T cell hybridomas. Inhibition
      studies revealed that the mouse peptide did not bind as well to major
      histocompatibility complex as the corresponding heterologous peptide. Both
      peptides gave rise to a T cell response after immunization. However, immunization
      with the heterologous peptide resulted in a response strictly directed to rat CII
      and the immunogen while immunization with the autologous peptide elicited T cells
      which reacted in a heteroclitic fashion, with a stronger response to the
      heterologous peptide than to the autologous peptide, and did respond to rat CII
      but not to mouse CII. We suggest that aspartic acid in position 266 results in a
      cryptic determinant in mouse CII which is neither recognized after CII
      immunization nor capable of tolerance induction. A glutamic acid at position 266,
      however, gives rise to an immunodominant epitope which is recognized by a large
      proportion of the T cells activated after immunization with heterologous CII.

PMID- 1378020
TI  - T cell clones with normal or defective O-galactosylation from a patient with
      permanent mixed-field polyagglutinability.
AB  - To delineate the extent of O-galactosyltransferase deficiency within the lymphoid
      lineage, monoclonal antibody specific for the Thomsen-Friedenreich (TF) antigen
      (Gal beta 1----3GalNAc alpha 1-O-Ser/Thr) and its precursor the Tn antigen
      (GalNAc alpha 1-O-Ser/Thr) were applied to the flow cytometric analysis of
      peripheral blood lymphocytes from a patient with permanent mixed-field
      polyagglutinability (PMFP). We show that only a minor population of 4% expressed
      the Tn antigen which is in contrast to 93% of the patient's erythrocytes carrying
      the defect. Tn+ lymphocytes mainly belonged to the CD3+ subset, but were also
      CD19+ or CD16+. Both Tn+ and TF+ T cell clones from patient R. R. were
      established and shown to belong to the CD4+ or CD8+ antigenic subset. Three
      glycosyltransferase activities were determined in lysates from these clones: all
      Tn+ clones were deficient in UDP-Gal: GalNAc alpha 1-O-Ser/Thr beta 1----3
      galactosyltransferase (beta 3Gal-T) activity; by contrast this activity was
      present in all lysates from TF-expressing clones. UDP-GalNAc: polypeptide alpha-N
      acetylgalactosaminyltransferase (GalNAc-T) and UDP-Gal: GlcNAc-R beta 1----4
      galactosyl-transferase (beta 4Gal-T) exhibited similar activities in both Tn+ and
      TF+ T cell clones. As a consequence of defective O-galactosylation in Tn+ T
      cells, cell surface sialic acid of Tn+ clones was reduced by greater than 50%
      when compared to TF+ clones as demonstrated by sialic acid-specific labeling
      using fluoresceinated Limax flavus agglutinin(LA) and flow cytometry. The Tn
      phenotype of T cell clones was stable for more than 1 year of continuous
      expansion in vitro. These data demonstrate that in PMFP, T cells may also be
      affected by the O-galactosyltransferase deficiency which is accompanied by a
      substantial loss of cell surface sialic acid. However, the frequency of Tn+
      lymphocytes in peripheral blood from patient R.R. was strikingly low. These T
      cell clones should be useful to study the defect at a genetic level and the
      importance of O-linked carbohydrates for proper T cell function.

PMID- 1378021
TI  - CD45 isoform expression during T cell development in the thymus.
AB  - Various isoforms of leukocyte common antigen, or CD45, are expressed
      differentially on T cells at different stages of development and activation. We
      report studies on CD45 isoform expression on various subsets of human T cells
      using two- and three-color flow cytometry and cell depletion. Bone marrow cells
      that were depleted of CD3+ and HLA-DR+ cells were CD45RA-RO-. The earliest CD3
      CD4-CD8-CD19- thymocytes were CD45RO- with 20%-30% CD45RA+ cells. The most
      prominent population of CD4+CD8+ double-positive thymocytes were CD45RA-RO+. Even
      the CD4+CD8+ blasts were greater than 90% CD45RO+. About 80% of single-positive
      thymocytes (CD4+CD8- or CD4-CD8+) were also CD45RO+. Only 4.3% of CD4+ and 18% of
      CD8+ single-positive thymocytes were CD45RA+. In contrast, cord blood T cells
      which represent the stage that immediately follows single-positive thymocytes,
      contained 90% CD45RA+ cells. Thus, in terms of CD45 isoform expression, single
      positive thymocytes are more like double-positive cells than cord blood T cells.
      These results suggest the following sequence of CD45 isoform switching during T
      cell development: CD45RA-RO- or RA+RO- (double-negative thymocytes)----RA-RO+
      (double-positive and most single-positive thymocytes)----RA+RO- (cord blood T
      cells), the last switch from CD45RO to CD45RA occurring as a final step of
      maturation in the thymus.

PMID- 1378022
TI  - Expression of the complement regulatory proteins CD21, CD55 and CD59 on Burkitt
      lymphoma lines: their role in sensitivity to human serum-mediated lysis.
AB  - On a panel of nine human B cell lines we showed that the expression of the
      complement regulatory factors complement receptor type 2 (CR2; CD21), decay
      accelerating factor, (DAF; CD55) and homologous restriction factor (HRF20, CD59)
      is not correlated. All lines expressed DAF, six lines carried detectable amounts
      of CR2 and three carried HRF20. Upon incubation in human serum, under conditions
      which allowed the activation of complement through the alternative pathway, the
      CR2-carrying lines bound C3 fragments and two of them (Ramos and one of its two
      sublines) were damaged. These two lines had the lowest DAF expression, less than
      50% of the cells reacted with the IA10 monoclonal antibody. By modulating the
      expression of the complement regulatory molecules, the lytic sensitivity of the B
      cell lines could be altered. Blockade of DAF on the HRF20-, CR2+ lines with the
      specific monoclonal antibodies increased their sensitivity to lysis by human
      serum. With the DAF- and HRF20+ cells significant lytic effect was obtained only
      when they were pretreated with both of the specific antibodies. Interferon-gamma
      or tumor necrosis factor-alpha treatment elevated the amount of CR2 on the low
      CR2 expressor line (Ramos/HR1K) which thereafter bound higher amounts of C3
      fragments and was lysed when incubated in human serum. This line had relatively
      low DAF level and lacked HRF20. The cytokine treatment did not alter the
      expression of these molecules. The CR2+ Ramos and the CR2- Rael cells were
      treated with 5-azacytidine which induced HRF20 and increased DAF expression. In
      parallel with this change Ramos cells became resistant to C-mediated lysis. The
      experiments with the panel of human B cell lines showed thus that cytolysis
      through activation of complement in homologous serum can be regulated at several
      steps by cell surface molecules. While expression of CR2 was required for C3
      fixation, DAF and HRF20 inhibited lysis. By independent modulation of the
      quantities of these molecules, cells acquired or lost their sensitivity.

PMID- 1378024
TI  - Species-specific restriction of complement by HRF20 (CD59) generated by cDNA
      transfection.
AB  - The 20-kDa homologous restriction factor (HRF20, CD59) is a phosphatidyl inositol
      anchored membrane glycoprotein that inhibits the formation of human complement
      membrane attack complexes. The cDNA of HRF20 was transfected into Chinese hamster
      ovary (CHO) cells resulting in expression of human HRF20 protein on the cell
      surface anchored via glycosylphosphatidyl inositol. The transfected CHO cells
      were resistant to human complement-mediated cell killing. However, the cells
      remained sensitive to rat and guinea pig complement. Therefore, species
      specificity between HRF20 and complement is maintained in HRF20 generated on the
      CHO cells following transfection with HRF20 cDNA.

PMID- 1378023
TI  - The calcium-binding proteins MRP8 and MRP14 form a membrane-associated
      heterodimer in a subset of monocytes/macrophages present in acute but absent in
      chronic inflammatory lesions.
AB  - Monocytes/macrophages expressing an epitope recognized by a monoclonal antibody
      27E10 are present in acute but are absent in chronic inflammatory disorders. This
      report shows that the 27E10 antigen is formed by noncovalent association of the
      two Ca(2+)-binding proteins MRP8 and MRP14 which belong to the S100 protein
      family. Identification has been confirmed immunochemically, by matrix-assisted UV
      laser desorption/ionization spectrometry and by partial amino acid sequencing.
      Surface expression of the MRP8/MRP14 complex on a subset of monocytes is reported
      for the first time and shown to be up-regulated in a Ca(2+)-dependent manner. The
      27E10 surface-positive monocytes isolated by cell separation techniques release
      high amounts of tumor necrosis factor-alpha and interleukin-1 beta in contrast to
      their 27E10 surface-negative counterparts thus emphasizing their role in
      inflammation.

PMID- 1378025
TI  - Distinct in vivo functions of two macrophage subpopulations as evidenced by
      studies using macrophage-deficient op/op mouse.
AB  - The op/op mice totally lack macrophage growth factor colony-stimulating factor
      (CSF)-1 and thus, by definition are completely depleted of CSF-1-dependent
      functions of the macrophage cell lineage. Moreover, they possess a severe and
      generalized macrophage deficiency. However, residual macrophages of these mice
      should still have normal CSF-1-independent functions. Studies designed to
      elucidate this issue have revealed that op/op mice are capable of normal in vivo
      phagocytic function and demonstrate normal humoral and cellular response
      postimmunization with sheep red blood cells. However, release of monokines such
      as tumor necrosis factor and granulocyte CSF following administration of
      endotoxin is severely impaired in op/op mice as compared with littermate
      controls. These studies suggest that the CSF-1-dependent macrophage population
      (absent in the op/op mouse) is primarily responsible for regulatory functions of
      these cells mediated by monokines, while the CSF-1-independent macrophage
      population (present in the op/op mouse) is primarily responsible for the
      classical macrophage functions in immunity such as phagocytosis, antigen
      processing and presentation.

PMID- 1378026
TI  - Firing characteristics of vestibular nuclei neurons in the alert monkey after
      bilateral vestibular neurectomy.
AB  - After destruction of the peripheral vestibular system which is not activated by
      moving large-field visual stimulation, not only labyrinthine-ocular reflexes but
      also optokinetic-ocular responses related to the "velocity storage" mechanism are
      abolished. In the normal monkey optokinetic-ocular responses are reflected in
      sustained activity changes of central vestibular neurons within the vestibular
      nuclei. To account for the loss of optokinetic responses after labyrinthectomy,
      inactivation of central vestibular neurons consequent on the loss of primary
      vestibular activity is assumed to be of major importance. To test this hypothesis
      we recorded the neural activity within the vestibular nuclear complex in two
      chronically prepared Rhesus monkeys during a period from one up to 9 and 12
      months after both vestibular nerves had been cut. The discharge characteristics
      of 829 cells were studied in relation to eye fixation, and to a moving small and
      large (optokinetic) visual stimulus producing smooth pursuit (SP) eye movements
      and optokinetic nystagmus (OKN). Units were grouped into different subclasses.
      After chronic bilateral vestibular neurectomy (BVN) we have found: (1) a rich
      variety of spontaneously active cells within the vestibular nuclear complex,
      which--as far as comparison before and after BVN is possible--belong to all
      subclasses of neurons functionally defined in normal monkey; and (2) no sustained
      activity changes which are related to the activation of the "velocity storage"
      mechanism; this is especially true for "pure-vestibular", "vestibular-pause" and
      "tonic-vestibular-pause" cells in normal monkey which show a "pure", "pause" and
      "tonic-pause" firing pattern after BVN. Neurons which are modulated by eye
      position are, however, modulated with the velocity of slow eye movements with
      comparable sensitivity during SP and OKN. Retinal slip is extremely rarely
      encoded. The results of the present study do not directly answer the question why
      the "velocity storage" mechanism is abolished after BVN but they suggest that
      only a small number of central vestibular cells may be inactivated by neurectomy.

PMID- 1378028
TI  - Laminin in the human embryo implantation: analogy to the invasion by malignant
      cells.
AB  - OBJECTIVE: To explore the possible similarities between the biochemical processes
      of embryo implantation and malignant invasion. DESIGN: The expression of a
      basement membrane (BM) glycoprotein laminin, a matrix binding cell surface
      receptor protein beta 1-integrin, and a BM collagen degrading metalloproteinase
      type IV collagenase, was studied in cultured human in vitro fertilized embryos.
      PATIENTS: Eight healthy women suffering from tubal infertility were participating
      in the IVF program in the Department of Obstetrics and Gynecology in University
      Hospital of Oulu. Twenty oocytes and 110 pre-embryos that were not transferred
      for the fertilizations were used in this study. MAIN OUTCOME MEASURES:
      Fibronectin, laminin, beta 1-integrin, and type IV collagenase immunoreactive
      proteins were studied in embryos by immunoperoxidase staining, and type IV
      collagen degrading activity was measured from the culture media of the embryos.
      RESULTS: Laminin and beta 1-integrin were expressed in the early human embryos
      before the time of implantation. Type IV collagen degrading activity and the 72
      kd-type IV collagenase immunoreactive protein were expressed at the time of
      implantation. Laminin supported the expression of type IV collagenase.
      CONCLUSIONS: The expression of laminin, beta 1-integrin, and type IV collagenase
      in vitro are temporally in good correlation with the time of the implantation in
      vivo. Laminin and beta 1-integrin can relate to the attachment of the embryos to
      the uterine BM and type IV collagenase to the degradation of the BM collagen
      during the implantation. Laminin can augment the process locally.

PMID- 1378029
TI  - Expression of loricrin is negatively controlled by retinoic acid in human
      epidermis reconstructed in vitro.
AB  - In epidermis, the last steps of keratinocyte differentiation are characterized by
      the covalent cross-linking of cornified envelope precursors such as involucrin
      and loricrin, a hydrophobic protein recently described in mouse and human
      epidermis. In situ hybridization of normal human skin sections with a human
      loricrin cRNA probe and immunolabeling with an antiserum directed against a
      synthetic peptide corresponding to the carboxyterminus of human loricrin revealed
      the presence of loricrin transcripts and protein in the granular layers of
      epidermis. In human epidermis reconstructed in vitro by growing keratinocytes on
      dermal equivalents, loricrin and loricrin mRNAs were also restricted to granular
      cells, but their amounts seemed higher than in epidermis from skin biopsies. The
      reactivities for both loricrin and loricrin mRNAs were abolished by a treatment
      of the cultures with a retinoic acid concentration (10(-6) M) provoking a
      complete inhibition of terminal epidermal differentiation (parakeratosis). Thus,
      the regulation of loricrin synthesis is different from that of another envelope
      precursor, involucrin, which does not seem to be significantly modulated by
      retinoic acid. Together with the well-documented inhibition of epidermal
      transglutaminase by retinoic acid, our results provide a molecular basis for the
      inhibition of cornified envelope formation by retinoic acid.

PMID- 1378027
TI  - Somatotopic termination of the spino-olivary fibers in the cat, studied with the
      wheat germ agglutinin-horseradish peroxidase technique.
AB  - Terminal sites of the spino-olivary fibers (SOFs) were examined by the
      anterograde transport of wheat germ agglutinin-horseradish peroxidase in the cat.
      The tracer was injected at various spinal cord levels from the first cervical to
      the caudal segments. The SOFs derived from the C1-T1 segments terminated medially
      in the caudal half (levels II-VIII of Brodal) of the medial accessory olive
      (MAO), which projects to the A zone of the cerebellar cortex, whereas the SOFs
      derived from the L6-S1 segments terminated laterally in the caudal half (levels I
      VIII) of the MAO. No projections were found from the T2-L5 segments to the MAO.
      In the dorsal accessory olive (DAO), the SOFs terminated at levels III-XIV; the
      DAO projects to the B zone and the C1 and C3 zones of the cerebellar cortex. The
      SOFs derived from the C1-C4 segments terminated in the most medial part of the
      DAO (levels III-XIV), followed laterally by those from the C5-T1 segments.
      Further laterally, the SOFs derived from the T2-L5 and the L6-S1 segments
      terminated in the mediolateral order at levels V-XIV. The SOFs from the L6-S1
      segments occupied the most lateral part of the DAO. The present study
      demonstrates that there is a distinct somatotopic termination of the SOFs in the
      mediolateral order in the caudal MAO and the DAO.

PMID- 1378030
TI  - Effects of vitamin A on collagen metabolism by cultured rat liver cells.
AB  - Conflicting results have been reported concerning the phenotypes of collagen
      produced by cultured Ito cells. These variations may be attributed to differences
      in pretreatment, i.e., with or without vitamin A to facilitate the separation of
      Ito cells. In the present study, the effects of vitamin A on collagen metabolism
      by Ito cells and hepatocytes of rats were analyzed. In cultured Ito cells,
      staining reactions to type I collagen increased, and those to type IV collagen
      and laminin decreased after pretreatment with vitamin A. The rate of collagen
      synthesis by Ito cells decreases significantly by treatment with vitamin A. The
      decrease was clearer in degraded collagen than in intact collagen. The synthesis
      of type I collagen increased and that of type IV collagen significantly decreased
      in Ito cells by treatment with vitamin A. In the hepatocytes, the staining
      reaction to type I collagen increased with vitamin A pretreatment. The net
      collagen and type III collagen synthesis in hepatocytes decreased by treatment
      with vitamin A. These results indicate that vitamin A modifies collagen
      metabolism in different cell types in different ways.

PMID- 1378031
TI  - The sequential change of serum 2',5' oligoadenylate synthetase in different
      infectious patterns of duck hepatitis B virus in ducks in experimental
      transmission.
AB  - Duck hepatitis B virus (DHBV) shows clear age-dependent infectious patterns like
      that of Hepatitis B virus, and many factors have been assumed to have a role in
      the persistence of the infection. In the present study, the activities of the
      interferon-induced enzyme 2',5' oligoadenylate synthetase (2,5AS) were observed
      sequentially in the serum of ducks experimentally infected with DHBV on posthatch
      days 1, 7 and 14. These were compared with the infectious pattern to investigate
      whether the endogenous interferon response after infection in ducks of different
      ages has a major role in its determination. The infectious pattern of DHBV in 1
      day-old ducks was persistent without hepatitis and the others were transient with
      hepatitis. Persistently infected ducks showed significantly lower activities of
      2,5AS compared with those with transient hepatitis, which resulted in a rapid
      elimination of DHBV. Although 1-day-old ducks showed significantly high 2,5AS
      compared with non-infected ducks, interferon response alone appeared to be
      insufficient for the elimination of DHBV. The immune response seemed necessary
      for the complete elimination of DHBV by way of evoking hepatitis and stimulating
      more interferon response during the usual infectious course. The interferon
      system alone did not seem to have a critical role in determining the infectious
      pattern. Other factors, including the immune response to the virus, seemed to
      have a major role in this problem.

PMID- 1378033
TI  - Involvement of cyclic adenosine 3',5'-monophosphate in methylation during 1
      methyladenine production by starfish ovarian follicle cells.
AB  - Resumption of meiosis in starfish oocytes is induced by 1-methyladenine (1-MeAde)
      produced by ovarian follicle cells under the influence of a gonad-stimulating
      substance (GSS). With respect to 1-MeAde production, the effect of GSS on
      follicle cells results in the receptor-mediated formation of cyclic AMP (cAMP).
      It has also been reported that methylation is involved in 1-MeAde production by
      GSS. This study was undertaken to determine whether cAMP is the agent responsible
      for mediating methylation in 1-MeAde biosynthesis by isolated follicle cells of
      the starfish Asterina pectinifera. Methionine and selenomethionine enhanced 1
      MeAde production by GSS in follicle cells. These stimulatory effects were
      dependent on the GSS concentration. Production of 1-MeAde by GSS was inhibited by
      ethionine and selenoethionine, competitive inhibitors of methionine. Like GSS, 1
      MeAde production induced by concanavalin A, trypsin, and 3-isobutyl-1
      methylxanthine (IBMX), which stimulated cAMP accumulation in follicle cells, was
      influenced by methionine and its related compounds. In contrast, although 1
      methyladenosine (1-MeAde-R) induced 1-MeAde production by follicle cells without
      increasing cAMP levels, methionine and its related compounds had no effect. Use
      of [methyl-14C]methionine showed that a radiolabel was incorporated into 1-MeAde
      during incubation with GSS and IBMX, but not with 1-MeAde-R. These results
      strongly suggest that cAMP plays an important role in the process of methylation
      during 1-MeAde biosynthesis induced by GSS.

PMID- 1378032
TI  - Circulating tumor-associated antigens detected by monoclonal antibodies against
      the polypeptide core of mucin--comparison of antigen MUSE11 with CA15-3.
AB  - The antigen MUSE11 detected by a monoclonal antibody (MAb) is an adenocarcinoma
      associated antigen, while CA15-3 is a representative breast cancer-associated
      antigen detected by MAbs 115D8 and DF3. MAb MUSE11 showed higher binding activity
      to a synthetic peptide corresponding to the tandem repeat motif of the mucin core
      protein than that of MAb DF3, although MAb DF3 also had a significant binding
      activity indicating that MAbs MUSE11 and DF3 could recognize an identical
      polypeptide core. The reactivity of MAb DF3 to a breast cancer cell line MRK-neu
      1 was completely abolished by neuraminidase treatment whereas that of MAb MUSE11
      was partly conserved. The simultaneous measurement of the antigens MUSE11 and
      CA15-3 in sera from 35 cancer patients demonstrated that the incidence of
      abnormal serum level of CA15-3 was lower than that of antigen MUSE11. These data
      suggest that at least a part of the structural basis for the difference between
      the serum levels of antigen MUSE11 and CA15-3 could be carbohydrate side chains
      including sialic acids.

PMID- 1378034
TI  - Neurotransmitters and stimulation of fluid reabsorption in migratory locust
      rectal cells.
AB  - Several biogenic amines enhance fluid reabsorption and the accumulation of cyclic
      adenosine-monophosphate (cAMP) in the rectum of the migratory locust but only 5
      hydroxytryptamine (5-HT) acts in a dose-dependent manner at low concentrations
      (between 10(-8) and 5.10(-7) M). Cyclic AMP is a second messenger of 5-HT, and
      its actions on fluid reabsorption are calcium-dependent. Polymyxin B (a protein
      kinase C inhibitor) mimics the actions of 5-HT on fluid reabsorption and on
      calcium-dependent cAMP accumulation. This suggests the presence of other sources
      of calcium and a possible relationship between several transduction systems
      within different rectal cells. The second messenger system mediating the 5-HT
      antidiuretic message differs from those involved in the transduction of the known
      locust antidiuretic hormones.

PMID- 1378035
TI  - Aeromonas allosaccharophila sp. nov., a new mesophilic member of the genus
      Aeromonas.
AB  - Phenotypic and genetic studies were performed on some atypical aeromonas strains
      of uncertain taxonomic position. 16S rRNA gene sequence analysis revealed that
      these strains represent a hitherto unknown genetic line within the genus
      Aeromonas, for which the name Aeromonas allosaccharophila sp. nov. is proposed.
      The type strain is CECT 4199.

PMID- 1378037
TI  - Nuclear and mitochondrial ribosomal RNA variability in the obscura group of
      Drosophila.
AB  - Parts of 28S (nuclear) and 12S (mitochondrial) ribosomal RNA of Palearctic,
      Nearctic and African species of the obscura group have been sequenced by the
      direct method of sequencing. Rates of nucleotide substitutions in both molecules
      were compared. The nucleotide divergence is higher in the mitochondrial rRNA.
      Average distances of species taken in pairwise were compared to results obtained
      with the melanogaster subgroup: the divergence of nuclear rRNA appears lower,
      that of the mtDNA higher whereas genetic distances (allozymes) and sncDNA
      distances are similar. Noticeable variability of evolutionary rates can be
      observed even in low taxonomical levels. Phylogenetic trees for the obscura group
      are in general agreement with those obtained with other characters.

PMID- 1378036
TI  - A nitrate reductase gene of the cyanobacterium Synechococcus PCC6301 inferred by
      heterologous hybridization, cloning and targeted mutagenesis.
AB  - DNA probes from the narG gene of Escherichia coli, which encodes the large
      polypeptide of respiratory nitrate reductase, show cross-hybridization at low
      stringency to a single region of the genome of the cyanobacterium Synechococcus
      PCC6301. This segment of cyanobacterial DNA was cloned as the insert of plasmid
      pDN1 and characterized. RNA complementary to pDN1 was shown to be substantially
      more abundant in nitrate grown cells of Synechococcus PCC6301 than in ammonium
      grown cells, thus parallelling the nitrate induction and ammonium repression of
      nitrate reductase activity in cultures of this cyanobacterium. A mutant of
      Synechococcus PCC6301 deficient in nitrate reductase activity was obtained after
      a potentially mutagenic transformation treatment using pDN1 as a donor. This
      mutant was restored to the wild type phenotype following stable integrative
      transformation with pDN1 DNA. Taken together these data suggest that pDN1 might
      encode a polypeptide of nitrate reductase. pDN1 is distinct from three clones of
      genes involved in nitrate assimilation that were isolated previously from the
      related cyanobacterium Synechococcus PCC7942 (Kuhlemeier et al., 1984a, J. Bact.
      159, 36-41, and 1984b, Gene 31, 109-116).

PMID- 1378039
TI  - Interaction of lectins with human IgE: IgE-binding property and histamine
      releasing activity of twelve plant lectins.
AB  - We examined the IgE-binding reaction and the histamine-releasing response of
      basophils to a panel of 12 lectins: concanavalin A (Con A), Lens culinaris
      hemagglutinin (LcH), Pisum sativum agglutinin (PSA), wheat germ agglutinin (WGA),
      soybean agglutinin (SBA), Bauhinia purpurea agglutinin (BPA), peanut agglutinin
      (PNA), Ricinus communis agglutinin I (RCA-I), Lotus tetragonolobus agglutinin
      (Lotus A), Ulex europeus agglutinin I (UEA-I), phytohemagglutinin E (PHA-E) and
      phytohemagglutinin L (PHA-L), IgE from allergic patients bound with high affinity
      to Con A, LcH, PSA, RCA-I and PHA-E, and with lower affinity to WGA, BPA, Lotus A
      and UEA-I, but they did not bind to SBA, PNA or PHA-L. There was no apparent
      individual difference in the reactivity of IgE to these lectins between 10 IgE
      preparations from allergic patients. The binding to these lectins, except Lotus A
      and UEA-I, were competitively inhibited by the lectin-specific sugars or
      glycopeptide. Upon stimulation by Con A, LcH, PSA, WGA, RCA-1 and PHA-E,
      leukocytes from allergic patients showed a significant release of histamine, but
      cells from IgE-deficient subjects did not respond to these lectins. The histamine
      releasing responses by these lectins were also inhibited by specific sugars or
      glycopeptides.

PMID- 1378038
TI  - Transplantation of organs between species.
AB  - The shortage of organs from human donors for transplantation has stimulated a
      renewed interest in the use of organs from animals or xenografting. Such grafts
      can be transplanted between closely related species--concordant, or distantly
      related species--discordant. In this mini review the immune processes which cause
      rejection for each of these categories is described. Data demonstrating methods
      by which this rejection can be controlled are summarised and a possible approach
      to clinical application is described.

PMID- 1378040
TI  - Mast cell heterogeneity: evidence that mast cells isolated from various
      connective tissue locations in the rat display markedly graded phenotypes.
AB  - The present study has extended histochemical and functional investigations into
      rat mast cell heterogeneity using isolated mast cells from four connective tissue
      locations; the peritoneum, mesentery, lung and skin. On histological examination,
      mast cells from these locations displayed a range of phenotypes following
      formalin fixation and staining with Alcian blue/safranin O, suggesting the
      existence of both chondroitin sulphate and heparin proteoglycans in varying
      proportions in these cell types. Functional studies using the structurally
      diverse polycationic secretagogues, compound 48/80, the polyamino acids,
      polymyxin B, substance P, ACTH1-24, mastoparan, protamine sulphate, histone, d
      tubocurarine and ranitidine confirmed the existence of such phenotypic gradation.
      This investigation highlights the inappropriate usage of the terms CTMC and MMC
      which represent two phenotypic extremes between which a gradation of phenotypes
      clearly exists.

PMID- 1378041
TI  - Effects of adenosine on histamine release from human lung fragments.
AB  - The actions of adenosine on histamine release of human lung fragments were
      investigated. Histamine release was stimulated either with the calcium ionophore
      A23187 or with concanavalin A. Adenosine and its analogue 5'-N
      ethylcarboxamidoadenosine alone had no significant effect on basal release or on
      the release elicited by A 23187 or concanavalin A. However, in the presence of
      the adenosine receptor antagonist 8-[4-[[[[(2-aminoethyl)amino]
      carbonyl]methyloxy]-phenyl]-1, 3-dipropylxanthine (XAC), which itself did not
      affect the release, adenosine increased the stimulated histamine release. On the
      other hand, in the presence of the nucleoside transport inhibitor S-(p
      nitrobenzyl)-6-thioinosine (NBTI), adenosine caused a reduction in stimulated
      histamine release. NBTI itself caused a stimulation of release. Thus, a
      stimulatory effect of adenosine was seen in the presence of XAC, whereas an
      inhibitory effect was unmasked by NBTI. From these data it is concluded that
      adenosine exerts two opposing effects on histamine release in the human lung
      which neutralize each other: it inhibits release via a site antagonized by XAC,
      which presumably represents an A2 adenosine receptor, and it stimulates release
      via a mechanism that is blocked by NBTI, suggesting that adenosine needs to reach
      the interior of cells to exert this effect. The slight stimulatory effect of NBTI
      alone demonstrates that trapping intracellularly formed adenosine inside mast
      cells leads to sufficient concentrations of adenosine to stimulate histamine
      release. These findings suggest an important bimodal role of adenosine in
      regulating histamine release in the human lung.

PMID- 1378042
TI  - Effect of NZ-107, a newly synthesized pyridazinone derivative, on antigen-induced
      contraction of human bronchial strips and histamine release from human lung
      fragments or leukocytes.
AB  - The effects of a newly synthesized pyridazinone derivative, NZ-107, 4-bromo-5-(3
      ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone, and two well-known antiasthmatic
      drugs, amlexanox (orally active disodium cromoglycate-like drug) and disodium
      cromoglycate (DSCG) on antigen-, histamine- and leukotriene C4 (LTC4)-induced
      constriction of isolated human tracheal muscle, and histamine release from human
      lung tissues and leukocytes were investigated in vitro. In some experiments,
      salbutamol was used as a reference drug. NZ-107 inhibited antigen-, histamine-
      and LTC4-induced contraction of tracheal muscle. Amlexanox and DSCG did not
      affect the contractile response of tracheal muscle caused by each stimulant.
      Salbutamol inhibited antigen-induced contraction of tracheal muscle. NZ-107,
      amlexanox, DSCG and salbutamol clearly inhibited the antigen-induced release of
      histamine and LTC4 from human lung tissue. The antigen-induced histamine release
      from atopic human leukocytes was inhibited by NZ-107 and amlexanox, but not by
      DSCG. Pretreatment with IL-3 did not alter antigen-induced contraction of
      tracheal muscle and histamine release from lung tissue, but antigen- or calcium
      ionophore A 23187-induced histamine release from leukocytes was clearly enhanced.
      Amlexanox inhibited the IL-3-induced enhancement of histamine release from
      leukocytes in the case of both stimuli, but NZ-107 and DSCG had no effect. These
      data suggest that NZ-107 has potent anti-allergic actions based on the inhibition
      of antigen-induced contraction of human tracheal muscle and mediator release from
      human lung tissue and leukocytes.

PMID- 1378043
TI  - Responses of isolated Japanese monkey tracheal muscle to allergic mediators.
AB  - The responsiveness of isolated Japanese monkey (Macaca fuscata) tracheal muscle
      to antigen, carbachol, histamine, leukotriene C4 (LTC4), U-46619 and substance P
      (SP) was compared to that of isolated human trachea. Weak but persistent
      contraction was observed after the addition of antigen to isolated Japanese
      monkey tracheal muscle passively sensitized with monkey serum containing IgE
      antibody against Japanese cedar (Cryptomeria japonica) antigen. Unlike monkey
      tracheal muscle, a fair amount of contraction was caused by the antigen in human
      tracheal muscle passively sensitized with human atopic serum. When chopped,
      passively sensitized monkey or human lung tissue was challenged with antigen, a
      significant level of histamine was released from these tissues. In Japanese
      monkey tracheal muscle, histamine and SP produced no contraction of tracheal
      muscle, whereas carbachol, LTC4 and U-46619 caused contraction in a dose
      dependent fashion. Contrary to the Japanese monkey, histamine and carbachol
      caused distinct contraction in tracheal muscle obtained from the cotton-headed
      tamarin (Saguinus oedipus). In human tracheal muscle, all test substances
      (carbachol, histamine, LTC4, U-46619 and SP) induced clear contraction. In lung
      parenchyma obtained from Japanese monkey, histamine induced a weak contraction,
      and this histamine-induced contraction was also inhibited by pyrilamine (H1
      receptor antagonist). These results indicate that antigen-induced contraction of
      isolated Japanese monkey tracheal muscle, passively sensitized with monkey atopic
      serum, is not a useful model for human allergic bronchoconstriction in vitro
      because of the unresponsiveness of tracheal muscle to histamine and SP.

PMID- 1378044
TI  - Ru 41.740 triggers human mononuclear blood cells to release tumor growth
      inhibitory factors in vitro.
AB  - Ru 41.740 (Biostim) is an immunostimulating drug of microbial origin which may
      stimulate human mononuclear blood cells (mainly monocytes) to release soluble
      factors which inhibit replication of several tumor cell lines in vitro. Since
      this effect may be of clinical importance in the treatment of cancer a number of
      tests have been conducted in order to find methods to augment this secretion. In
      vitro tests suggested that this non-specific antitumor activity of Biostim may
      not be enhanced by concomitant treatment of patients with inhibitors of cyclo
      oxygenase and lipoxygenases or by interferons alpha, beta, gamma or the
      hemopoietic growth factors GM-CSF and G-CSF.

PMID- 1378045
TI  - LY 186655, a phosphodiesterase inhibitor, inhibits histamine release from human
      basophils, lung and skin fragments.
AB  - LY 186655 (Tibenelast, Lilly) is a new phosphodiesterase inhibitor, not derived
      from the xanthine, possessing bronchodilating activity in animals. The aim of
      this work was to study the effect of LY 186655 and theophylline on histamine
      release from human leukocytes, skin and lung fragments. Histamine was measured
      using a spectrofluorometric method. Both drugs (3 x 10(-5)-3 x 10(-3) M)
      exhibited a dose-dependent inhibition on anti-IgE (1/2000)-induced histamine
      release from human leukocytes. At 3 x 10(-3) M, theophylline was significantly
      more effective than LY 186655 (mean inhibition 94 and 42%, respectively). On lung
      fragments, theophylline and LY 186655 (3 x 10(-5)-3 x 10(-3) M) caused strong and
      comparable inhibitory effects on anti-IgE (1/500)-induced histamine release with
      a mean inhibition reaching maximally 65%. Histamine release induced by compound
      48/80 (1 mg/ml) on sliced human foreskin was reduced with both drugs (3 x 10(-3)
      M) by about 37%. We conclude that LY 186655 inhibits in vitro immunological
      histamine release from human lung and cutaneous mast cells as well as basophils
      with a similar pattern of activity to theophylline.

PMID- 1378046
TI  - Transurethral resection of 1250 bladder tumours.
AB  - A total of 1250 bladder tumours were subjected to transurethral resection (891
      curative, 107 palliative operations, 252 TUR biopsies). Complication rate was
      9.9%, mortality rate 0.8%. In patients with primary tumours the 1-year recurrence
      rate after TUR was 23.8%, the 3-year rate was 36.6%, with an increase in
      proportion to stage. The 5-year survival rate was 66.5%. Within five years 9% of
      the patients died from tumour generalization, also with a rising tendency in
      proportion to stage. TUR as a curative method is suitable mainly for the removal
      of Ta and T1, under circumstances also of T2 G1-G2 tumours.

PMID- 1378047
TI  - Development of urethral stricture after transurethral prostatectomy: a
      retrospective study.
AB  - A total of 103 patients who were diagnosed to have benign prostatic hyperplasia
      (BPH) without preoperative urethral stricture and underwent transurethral
      prostatectomy (TURP) were evaluated retrospectively from patient charts. The
      incidence of urethral stricture development was calculated as 11.65% (12 out of
      103 patients). Among the aetiologic factors analyzed, the most important ones
      appeared to be postoperative infection, age of the patient, duration of
      postoperative catheterization and histology of the disease, in the order of
      significance in the development of urethral stricture after TURP.

PMID- 1378048
TI  - Optimal administration schedules of the newly synthesized platinum analog NK121
      and bleomycin analog NK313 in nude mice with squamous cell carcinoma.
AB  - To determine the optimal administration schedules of the newly synthesized, less
      nephrotoxic platinum analog NK121 and less pneumotoxic bleomycin analog NK313,
      the antitumor effects of 2 different injection schedules, (1) single injections
      on days 1, 5, and 9, (2) continuous infusion for 7 days, were compared in nude
      mice bearing human squamous cell carcinoma. Tumor growth delay was employed as
      the experimental endpoint of antitumor activity. Body weight and hematologic
      changes in the mice were also investigated as indications of drug toxicity after
      the combination treatment of NK121 and NK313. The antitumor effects of the 2
      analogs indicated higher responses with the single injections of NK121 and
      continuous infusion of NK313. In combination chemotherapy with NK121 and NK313,
      the highest antitumor effect was observed when mice were given NK121 by single
      injections followed by NK313 by continuous infusion. This sequence was also less
      toxic than a simultaneous treatment schedule, which was of weak clinical
      significance because of its low antitumor activity, severe weight loss, slight
      myelosuppression, and renal toxicity.

PMID- 1378049
TI  - Language intervention and disruptive behavior in preschool children with autism.
AB  - Disruptive behaviors are often exhibited by children with severe disabilities
      during difficult teaching tasks. Because learning verbal communication can be a
      difficult task for nonverbal children with autism, disruptive behaviors are
      common during such interventions. The purpose of this experiment was to assess
      whether the incorporation of parameters of natural language interactions and
      motivational techniques might reduce disruptive behavior during language teaching
      tasks. Within a repeated reversals design with order of conditions and number of
      sessions varied within and across children, treatment was conducted for two
      language teaching conditions. During one condition trials were presented serially
      in a traditional analog clinical format where the therapist presented
      instructions, prompts, and reinforcers for correct responses. The other condition
      incorporated parameters of natural language interactions and motivational
      techniques, such that stimulus items were functional and varied; natural
      reinforcers were employed; communicative attempts were reinforced; and trials
      were conducted within a natural interchange. Results showed that greater
      improvements in responding and considerably less (often negligible) disruptive
      behavior occurred during the natural language teaching conditions. Results are
      discussed with respect to their implications for improving language
      interventions, and with respect to reducing disruptive behavior without the need
      for specialized or severe interventions focused specifically on the disruptive
      behavior.

PMID- 1378050
TI  - A comparative study of development and symptoms among disintegrative psychosis
      and infantile autism with and without speech loss.
AB  - To investigate clinical pictures and the validity of disintegrative psychosis
      (DP) as defined in ICD-9, 18 cases of DP were compared with 51 and 145 cases of
      infantile autism (IA) with and without speech loss, respectively, on clinical
      variables. The DP cases showed clearer regression after more satisfactory
      development than the IA cases with speech loss. Around age 7, about 4 years after
      regression, those with DP were significantly more severely retarded than those
      with IA, yet both were similar in autistic symptomatology. EEG abnormalities and
      mothers 30 or older at delivery were significantly more common in the histories
      of those with DP than of those with IA. DP may be linked with IA having speech
      loss with regression in mental development as a common denominator.

PMID- 1378051
TI  - Transcriptional regulation of Bacillus subtilis glucose starvation-inducible
      genes: control of gsiA by the ComP-ComA signal transduction system.
AB  - The Bacillus subtilis glucose starvation-inducible transcription units, gsiA and
      gsiB, were characterized by DNA sequencing, transcriptional mapping, mutational
      analysis, and expression in response to changes in environmental conditions. The
      gsiA operon was shown to consist of two genes, gsiAA and gsiAB, predicted to
      encode 44.9- and 4.8-kDa polypeptides, respectively. The gsiB locus contains a
      single cistron which encodes a protein of unusual structure; most of its amino
      acids are arranged in five highly conserved, tandemly repeated units of 20 amino
      acids. The 5' ends of gsiA and gsiB mRNAs were located by primer extension
      analysis; their locations suggest that both are transcribed by RNA polymerase
      containing sigma A. Expression of both gsiA and gsiB was induced by starvation
      for glucose or phosphate or by addition of decoyinine, but only gsiA was induced
      by exhaustion of nutrient broth or by amino acid starvation. Regulation of gsiA
      expression was shown to be dependent upon the two-component signal transduction
      system ComP-ComA, which also controls expression of genetic competence genes.
      Mutations in mecA bypassed the dependency of gsiA expression on ComA. Disruption
      of gsiA relieved glucose repression of sporulation but did not otherwise
      interfere with sporulation, development of competence, motility, or glucose
      starvation survival. We propose that gsiA and gsiB are members of an adaptive
      pathway of genes whose products are involved in responses to nutrient deprivation
      other than sporulation.

PMID- 1378052
TI  - Identification of acoR, a regulatory gene for the expression of genes essential
      for acetoin catabolism in Alcaligenes eutrophus H16.
AB  - Two hundred thirty-nine base pairs upstream from acoXABC, which encodes the
      Alcaligenes eutrophus H16 structural genes essential for cleavage of acetoin, the
      2,004-bp acoR gene was identified. acoR encodes a protein of 668 amino acids with
      a molecular mass of 72.9 kDa. The amino acid sequence deduced from acoR exhibited
      homologies to the primary structures of transcriptional activators such as NifA
      of Azotobacter vinelandii, NtrC of Klebsiella pneumoniae, and HoxA of A.
      eutrophus. Striking similarities to the central domain of these proteins and the
      presence of a typical nucleotide-binding site (GETGSGK) as well as of a C
      terminal helix-turn-helix motif as a DNA-binding site were revealed. Between acoR
      and acoXABC, two different types of sequences with dual rotational symmetry [CAC
      (N11 to N18)-GTG and TGT-(N10 to N14)-ACA] were found; these sequences are
      similar to NtrC and NifA upstream activator sequences, respectively.
      Determination of the N-terminal amino acid sequence of an acoR'-'lacZ gene fusion
      identified the translational start of acoR. S1 nuclease protection assay
      identified the transcriptional start site 109 bp upstream of acoR. The promoter
      region (TTGCGC-N18-TACATT) resembled the sigma 70 consensus sequence of
      Escherichia coli. Analysis of an acoR'-'lacZ fusion and primer extension studies
      revealed that acoR was expressed at a low level under all culture conditions,
      whereas acoXABC was expressed only in acetoin-grown cells. The insertions of Tn5
      in six transposon-induced acetoin-negative mutants of A. eutrophus were mapped
      within acoR. On the basis of these studies, it is probable that AcoR represents a
      regulatory protein which is required for sigma 54-dependent transcription of
      acoXABC.

PMID- 1378054
TI  - TnphoA and TnphoA' elements for making and switching fusions for study of
      transcription, translation, and cell surface localization.
AB  - We describe a set of elements based on the transposon TnphoA for making
      transcriptional fusions to the lacZ gene and for making translational fusions to
      the phoA or lacZ structural gene. Each element can be switched, one for another,
      by homologous recombination, thereby allowing testing for transcription,
      translation, or cell surface localization determinants at the same site within a
      gene. We describe three kinds of elements for making each fusion type. Two kinds
      are transposition proficient (Tnp+): one encodes kanamycin resistance, and the
      other encodes tetracycline resistance. The third kind is transposition defective
      (Tnp-) and encodes kanamycin resistance. In addition, we describe one Tnp-
      element that has no reporter gene and encodes chloramphenicol resistance; this
      element is used primarily as a tool to aid in switching fusions. Switching is
      efficient because each element has in common 254 bp of DNA at the phoA end and
      187 bp (or more) of DNA at the IS50R end of TnphoA, and switching is
      straightforward because individual elements encode different drug resistances.
      Thus, switched recombinants can be selected as drug-resistant transductants, and
      they can be recognized as ones that have lost the parental drug resistance and
      fusion phenotype. Further, switching Tnp+ elements to Tnp- elements reduces
      problems due to transposition that can arise in P1 crosses or cloning
      experiments. Some TnphoA and TnphoA' elements cause polar mutations, while others
      provide an outward promoter for downstream transcription. This feature is
      especially useful in the determination of operon structures. Strategies for the
      use of TnphoA and TnphoA' elements in gene analysis are also described.

PMID- 1378053
TI  - Regulation of plasmid virulence gene expression in Salmonella dublin involves an
      unusual operon structure.
AB  - The 80-kb plasmid pSDL2 of Salmonella dublin Lane is essential for lethal
      systemic infection in experimental mice. A cluster of five plasmid genes,
      designated spvR, spvA, spvB, spvC, and spvD, is sufficient to express the plasmid
      related virulent phenotype. The spvR gene product has recently been identified as
      a positive regulator of spvB expression in the stationary phase of bacterial
      growth (F. C. Fang, M. Krause, C. Roudier, J. Fierer, and D. G. Guiney, J.
      Bacteriol. 173:6783-6789, 1991). In this study, we evaluated the role of SpvR in
      the transcription of the downstream virulence genes spvABCD. Analysis of mRNA
      synthesis revealed that SpvR promotes transcription of the downstream spvABCD
      genes in the stationary growth phase. Transcript mapping of the spv region
      demonstrated an unusual operon structure involving messages for spvA, spvAB,
      spvABC, and spvABCD. Quantitative measurement of transcription and of gene
      expression by use of translational spv-lacZ fusions suggested that SpvA, SpvB,
      SpvC, and SpvD are produced in decreasing abundance. Primer extension assays
      identified two transcriptional start sites 70 and 98 bp upstream of the start
      codon of spvA, but none upstream of spvB, spvC, or spvD. Deletion of a 320-bp
      EcoRI-ApaI segment that contains both start sites abolished expression of the
      downstream spvB and spvC genes. Our results establish a central function of SpvR
      as a positive regulator of the downstream spvABCD genes in the stationary phase
      of bacterial growth and indicate that the primary mechanism of regulation is by
      activation of promoters upstream of spvA.

PMID- 1378055
TI  - Molecular cloning of the rfb region of Klebsiella pneumoniae serotype O1:K20: the
      rfb gene cluster is responsible for synthesis of the D-galactan I O
      polysaccharide.
AB  - Previous chemical analyses identified two structurally distinct O polysaccharides
      in the lipopolysaccharide of Klebsiella pneumoniae serotype O1:K20 (C. Whitfield,
      J. C. Richards, M. B. Perry, B. R. Clarke, and L. L. MacLean, J. Bacteriol.
      173:1420-1431, 1991). The polysaccharides were designated D-galactan I and D
      galactan II; both are homopolymers of galactose. To begin investigation of the
      synthesis and expression of these O polysaccharides, we have cloned a 7.3-kb
      region of the chromosome of K. pneumoniae O1:K20, containing the his-linked
      rfbkpO1 (O-antigen biosynthesis) gene cluster. In Escherichia coli K-12 and
      Salmonella typhimurium, rfbkpO1 directed the synthesis of D-galactan I but not D
      galactan II. The cloned rfbkpO1 genes did not complement a mutation affecting D
      galactan II synthesis in K. pneumoniae CWK37, suggesting that another (unlinked)
      locus is also required for D-galactan II expression. However, plasmids carrying
      rfbkpO1 did complement a mutation in K. pneumoniae CWK43 which eliminated
      expression of both D-galactan I and D-galactan II, indicating that at least one
      function is common to synthesis of both polymers. Synthesis of D-galactan I was
      dependent on chromosomal galE and rfe genes. Hybridization experiments indicated
      that the rfbkpO1 sequences from different serotype O1 Klebsiella isolates showed
      some restriction fragment length polymorphism.

PMID- 1378056
TI  - The healing of segmental bone defects, induced by recombinant human bone
      morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical
      study in rats.
AB  - Subcutaneous implants of a recombinant human form of the bone-inducing protein
      rhBMP-2 (recombinant human bone morphogenetic protein-2) in rats have resulted in
      the local induction of endochondral bone formation. To test the osteoinductive
      activity of rhBMP-2 in an osseous location, we created five-millimeter segmental
      defects in the femora of forty-five adult male Sprague-Dawley rats. Two doses of
      lyophilized rhBMP-2 (1.4 or 11.0 micrograms) were implanted in each defect,
      together with guanidine-hydrochloride extracted demineralized rat-bone matrix as
      a carrier, and the results were compared with those in rats that had implantation
      of guanidine-hydrochloride extracted demineralized rat-bone matrix only. The
      formation and healing of bone were determined by radiographic, histological, and
      mechanical analysis. Both doses of rhBMP-2 induced formation of endochondral bone
      in the osseous defects in a dose-related manner. Implantation of 11.0 micrograms
      of rhBMP-2 yielded significant (p less than 0.05) bone formation, resulting in
      radiographic, histological, and mechanical evidence of union. Despite new-bone
      formation in the defects that had received 1.4 micrograms of rhBMP-2, no
      instances of union were observed.

PMID- 1378057
TI  - Progesterone receptor determined by immunocytochemical and biochemical methods in
      human breast cancer.
AB  - Immunocytochemical assay (ICA) of the progesterone receptor (PgR) was performed
      on 152 patients with stage I-II breast cancer. We employed the rat monoclonal
      antibody KD-68 and a peroxidase/antiperoxidase displaying system. The results
      obtained by ICA (Pg(RICA)) were compared with those by the biochemical dextran
      coated charcoal assay (PgRDCC). Comparing the two methods we found an overall
      agreement (accuracy) of 77.5%, a PgR(ICA) sensitivity of 83.5% and a specificity
      of 73%. Both methods were significantly associated with oestrogen receptor
      expression, detected by DCC (P less than 0.001 for PgRDCC and P = 0.0014 for
      PgR(ICA)). No significant association was found between PgR(ICA) or PgRDCC and
      the other clinicopathological features analysed. After a median follow-up of 36
      months, the overall survival probability was 91% in PgRDCC-positive versus 81.5%
      in PgRDCC-negative patients (log-rank test, chi 2 = 0.91) compared to 87.5% in
      PgR(ICA)-positive versus 82% in PgR(ICA)-negative ones (log-rank test, chi 2 =
      0.93). Disease-free survival probability was 74.5% in both PgRDCC-positive and
      PgRDCC-negative patients (log-rank test, chi 2 = 0.02) compared to 78% in
      PgR(ICA)-positive versus 71.5% in PgR(ICA)-negative cases (log-rank test, chi 2 =
      0.37). The present study demonstrates that ICA is a reliable method to detect
      PgR, correlating well with the DCC assay. Moreover, the ICA assay seems to
      provide clinical information complementary to the biochemical method. The
      definition of its prognostic value in operable breast cancer needs additional
      studies, particularly in node-negative patients.

PMID- 1378059
TI  - Detection of Mycoplasma hyopneumoniae by using rRNA-oligodeoxynucleotide
      hybridization.
AB  - A system that uses rRNA-oligodeoxynucleotide hybridization was developed for the
      detection of Mycoplasma hyopneumoniae. Synthetic oligonucleotide MHP1 was
      hybridized specifically with M. hyopneumoniae. Furthermore, the detection of M.
      hyopneumoniae in clinical samples, such as bronchoalveolar lavage fluid and lung
      lesions from experimentally infected pigs, was evaluated by this assay. The
      evidence obtained from the assay indicated that the system can be used to
      efficiently diagnose mycoplasmal pneumonia of swine. Additionally, a
      nonradioisotopic system with chemiluminescence detection was tested. This system
      was 10-fold less sensitive than a test that used radioisotopes.

PMID- 1378058
TI  - Length polymorphisms in tRNA intergenic spacers detected by using the polymerase
      chain reaction can distinguish streptococcal strains and species.
AB  - Intergenic tRNA spacers from strains of streptococcal groups A, B, and G were
      amplified by using the polymerase chain reaction (PCR) at low stringency with
      consensus tRNA gene primers. Cloning and sequencing showed that many of the
      homologous intergenic spacers differed in length between species. The sequences
      of the tRNA genes that flank these polymorphic spacers were determined and used
      to synthesize fully complementary primers. With these primers at high stringency,
      PCR products which varied in lengths from 53 to 71 bp, depending on the species
      or strain, were obtained from streptococcal DNAs, even in the presence of a 1,000
      fold mass excess of human DNA. PCR products, the lengths of which could also be
      used for classification, were obtained at high stringency from a few genera
      closely related to Streptococcus. No products were obtained from genomic DNAs
      from more distantly related genera. Production of species- or strain-specific
      tRNA intergenic length polymorphisms with primers that generate characteristic
      products from a variety of species within the same genus should be applicable to
      many organisms, including those that would otherwise be difficult to culture or
      identify.

PMID- 1378060
TI  - Comparison of DNA fingerprints and somatic serotypes of serogroup B and E
      Pasteurella multocida isolates.
AB  - The DNA fingerprint profiles and somatic serotypes of 71 Pasteurella multocida
      capsule serogroup B isolates, 13 capsule serogroup E isolates, and 16 somatic
      reference serotype strains were compared. Each of the 16 reference somatic
      serotypes had a unique DNA fingerprint profile with the HhaI restriction
      endonuclease. Fifty-four serogroup B isolates (isolated from classical cases of
      hemorrhagic septicemia) reacted with somatic serotype 2 or 5 antiserum and had
      DNA fingerprint profiles which resembled that of the serotype 2 reference strain.
      Seven DNA fingerprint profiles were found among 16 serogroup B strains
      representing other somatic serotypes. The DNA fingerprints of these isolates were
      different from the fingerprints of the 16 somatic reference serotype strains. All
      13 serogroup E isolates had identical somatic serotypes and identical DNA
      fingerprint profiles when the HhaI endonuclease was used. The HhaI fingerprint
      profile of the serogroup E isolates did not match any fingerprint profile of the
      reference somatic serotype strains. Following DNA profiling with the HhaI
      endonuclease, the 13 serogroup E isolates were differentiated sequentially with
      HpaII restriction endonuclease. A descriptive identification epithet for P.
      multocida isolates was constructed. The descriptive epithet consists of serologic
      identification and sequential DNA profiles with restriction endonucleases HhaI
      and HpaII, respectively. DNA fingerprinting of P. multocida is a precise
      characterization method. In conjunction with serologic typing, it can further
      classify P. multocida isolates for epidemiologic studies.

PMID- 1378062
TI  - Monoclonal antibodies specific for Clostridium difficile toxin B and their use in
      immunoassays.
AB  - Five mouse monoclonal antibodies (MAbs) against Clostridium difficile toxin B
      have been raised and characterized. Three of them were immunoglobulin M (IgM)
      antibodies (6B10, 6G3, and 10B9), and the other two were of the IgG1 isotype (9E5
      and 17G2), recognizing specifically two distinct epitopes on the toxin B
      molecule. No MAb was able to neutralize cytotoxic activity significantly. The two
      IgG1 MAbs were purified and applied to various immunodiagnostic assays. MAbs
      coupled to latex beads were used for specific removal of toxin B from cytotoxic
      samples and for agglutination assay. An indirect sandwich enzyme-linked
      immunosorbent assay with MAb 9E5 or 17G2 as the capture antibody was established
      for identification of toxin B with a lower detection limit of 5 ng/ml.

PMID- 1378061
TI  - Mapping the major antigenic domains of the native flagellar antigen of Borrelia
      burgdorferi.
AB  - Purified flagellar protein (p41) of Borrelia burgdorferi (strain B31) was
      subjected to chemical cleavage with hydroxylamine or proteolysis with V8
      protease, endoproteinase Asp-N, or alpha-chymotrypsin. The resulting polypeptides
      were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and
      their positions in the published DNA sequence of the p41 protein were determined
      by amino-terminal sequencing and amino acid analysis. Epitope specificities of
      antibody binding by a monoclonal antibody raised by immunization of mice with
      purified flagella and pooled sera from patients with multiple erythema migrans,
      late Lyme borreliosis, or secondary syphilis were analyzed by Western blots
      (immunoblots) of peptides transferred to Immobilon polyvinylidene difluoride
      filters. The major epitope binding one murine monoclonal antibody (158) was
      localized to a carboxy-terminal domain that includes residues 300 to 336. The
      dominant epitopes binding human polyclonal antibodies are in the central portion
      of the molecule (residues 182 to 218) that is not conserved compared with other
      bacterial flagellins. Additional reactive epitopes were identified in the amino
      terminal domain of the protein. Sera from patients with syphilis bound strongly
      to the amino-terminal conserved domain, providing a structural basis for cross
      reactivity seen in standard enzyme-linked immunosorbent assays, but not to the
      central part of the molecule. Specific and cross-reactive antigenic determinants
      need to be considered in the design of improved immunodiagnostics for spirochetal
      diseases.

PMID- 1378063
TI  - Ribotyping of Helicobacter pylori from clinical specimens.
AB  - Ribotyping is a method used to type strains of bacteria by analyzing the
      restriction enzyme digestion patterns of the rRNA genes. This method was applied
      to 126 strains of Helicobacter pylori from 100 unrelated symptomatic patients who
      had endoscopies done and to 15 strains from 15 infected subjects from seven
      families. Analysis of the rRNA gene patterns revealed 77 distinct ribotypes from
      the 100 patients. From 15 of these subjects, isolates were recovered from antral
      mucosal biopsies at follow-up endoscopy. All follow-up isolates from the same
      patient, with one exception, yielded identical digest patterns. This patient had
      strains with two distinct digest patterns obtained from a set of three isolates
      cultured from biopsy specimens taken at different times. Five patients who had
      isolates recovered from different sites in the stomach (antrum, gastric body,
      duodenum, and pyloric channel) showed ribotyping patterns which were identical
      for each patient yet distinct between patients. In seven family groups studied,
      identical digest patterns were detected in members of two families, with
      variability in strains detected among members of the remaining families. This
      study demonstrates that ribotyping provides a useful, reliable, reproducible, and
      highly discriminatory typing scheme for the study of H. pylori infection.

PMID- 1378064
TI  - Keratinization of palatal mucosa beneath metal-based removable partial dentures.
AB  - Exfoliative cytology provides a non-invasive method of examining changes in
      epithelial differentiation beneath dentures. Cell sampling by mechanical scraping
      may introduce errors due to collection of deeper epithelial cells, therefore an
      alternative sampling method was evaluated. Cells collected from the hard palates
      of 24 dentate subjects using either a wooden tongue depressor or transparent,
      adhesive-coated tape were fixed and stained by Papanicolaou's technique. The
      percentage of the total epithelial cells counted that were anucleate (the
      orthokeratinization index) was 99.95 per cent using the tape technique but 15 per
      cent lower using the smear technique. It appears that the tape technique gives a
      more accurate representation of the orthokeratinization of superficial cell
      layers. The tape technique was used to examine epithelial changes beneath tooth
      supported removable partial dentures (RPDs). In 26 subjects, who had worn cobalt
      chromium based RPDs for at least 6 months, samples taken from beneath the metal
      denture base had a 50 per cent lower orthokeratinization index than those from
      uncovered areas of the palate.

PMID- 1378066
TI  - Diversity in MHC class II ovalbumin T cell epitopes generated by distinct
      proteases.
AB  - It is generally accepted that a limited number of T cell epitopes are generated
      by APC from an immunogenic protein. To ascertain the number of determinants on
      OVA recognized in the context of the H-2s haplotype, we generated 19 T-T
      hybridomas against OVA and H-2s and we synthesized 46 overlapping peptides
      spanning the entire protein. Eighteen T-T hybrids were stimulated by eight
      different peptides. The peptide recognized by one T cell hybrid was not
      identified. The effect of four protease inhibitors on the processing and
      presentation of OVA by the LS.102.9 B cell hybridoma seemed to implicate several
      groups of proteases in the processing of this Ag. Alkylation of cysteine residues
      with iodoacetic acid showed in a few cases a dramatic decrease in the capacity of
      OVA to stimulate T-T hybrids recognizing cysteine-free peptides. In contrast, two
      T-T hybrids recognizing cysteine containing peptides were not affected by the
      alkylation, suggesting that alkylation inhibited the processing of OVA without
      affecting peptide interaction with class II MHC molecules. These data demonstrate
      that the repertoire of peptides generated by APC from OVA is not limited to one
      or few immunodominant peptides, and results from the activity of several
      endopeptidases and/or exopeptidases. In addition, the structure of the Ag (native
      or denatured) was shown to affect the efficiency with which different epitopes
      are generated.

PMID- 1378065
TI  - Wild mice express an Ig V lambda gene that differs from any V lambda in BALB/c
      but resembles a human V lambda subgroup.
AB  - The lambda L chain locus in the inbred mouse strains commonly used in the
      laboratory contains a limited number of germ-line genes; only three V lambda and
      three functional J lambda-C lambda genes have been identified in BALB/c mice.
      Previous studies indicated that wild mice may have a considerably expanded number
      of C lambda genes, as judged by the number of DNA restriction fragments that
      hybridize to C lambda probes derived from BALB/c. In order to evaluate the
      expression of these putative lambda genes, we have determined sequences of cDNA
      encoding lambda-chains in hybridomas from wild mice of the subspecies Mus
      musculus musculus from two different geographic regions, Denmark and
      Czechoslovakia. Two of these hybridomas produce L chains with J and C regions
      that are very similar to those of BALB/c lambda 1 chains, but the V regions of
      these L chains are only approximately 40% identical in amino acid sequence to the
      known murine V lambda. Indeed, these wild mouse V lambda are closer in sequence
      to human V lambda than they are to BALB/c V lambda, especially to human V lambda
      of subgroup VI, with which they share an unusual two-residue insertion in
      framework 3; L chains bearing V regions of this rare human type have a marked
      tendency to enter into amyloid deposits. These findings suggest that similar V
      lambda may be widespread in mammalian populations, although analysis by Southern
      blotting indicates that they are not found in BALB/c mice. A third hybridoma
      produces a L chain whose V lambda resembles BALB/c V lambda 1. The J lambda and C
      lambda segments of the cDNA encoding all three hybridoma L chains are identical;
      evidently, of the several putative genes that hybridize to C lambda 1 probes, one
      is expressed preferentially.

PMID- 1378067
TI  - Role of binding pockets for amino-terminal peptide residues in HLA-B27
      allorecognition.
AB  - The peptide binding site of HLA-B27 and other class I Ag consists of a series of
      pockets that bind peptide side chains. Two of these pockets interact with the
      amino-terminal peptide residue (pocket A) and with the highly conserved second
      residue (pocket B). In this study, the role of pockets A and B in HLA-B27
      specific T cell allorecognition has been analyzed. Four HLA-B27 mutants with
      single or double changes in pocket B (24T----A, 45E----M, 67C----V, and 24,67T,C-
      --A,V) and three mutants with single changes in pocket A (163E----T, 167W----S,
      and 171Y----H) were constructed by site-directed mutagenesis and expressed in
      HMy2.C1R cells after DNA-mediated gene transfer. These transfectants were used as
      target cells in cytotoxicity assays with a series of HLA-B27-specific CTL. All
      the mutations analyzed affected allorecognition by a significant proportion of
      the CTL tested, but no single change abrogated recognition by all CTL. The global
      effects of each mutation on allorecognition were comparable to one another,
      except for the effect of the change at position 67, which was smaller. The
      behavior of individual CTL with the mutants was very diverse, ranging from CTL
      that did not recognize most of the mutants to CTL recognizing all of them. Thus,
      some alloreactive CTL can withstand drastic alterations in pockets A and B. Two
      CTL showed heteroclytic effects towards the V67 and M45 mutants. CTL behavior
      with the H171 mutant was closely parallel to that with the B*2703 subtype, having
      a single Y----H change at position 59. This parallelism correlates with the
      similar role of Tyr59 and Tyr171 in establishing hydrogen bonds with the amino
      termini of HLA-B27-bound peptides. The results demonstrate that altering the
      structure of pockets that interact with the amino-terminal first and second
      residues of HLA-B27-bound peptides significantly affects recognition by
      alloreactive CTL, and they strongly suggest widespread peptide involvement in HLA
      B27 allorecognition.

PMID- 1378068
TI  - Enhancing the immunogenicity of a permissive binding T cell epitope derived from
      the simian immunodeficiency virus-encoded negative regulatory factor.
AB  - Using the murine system we have analyzed an immunogenic T cell peptide epitope
      corresponding to amino acids 96-112 of the simian immunodeficiency virus-negative
      regulatory protein sequence. This epitope was unusual in that it was strongly
      immunogenic in mice of five of the six H-2 haplotypes tested. We generated a T
      cell hybridoma (SVNF) specific for this peptide in order to determine how
      manipulating the peptide might alter its immunogenicity. Substitution analysis
      showed that His 103, Pro 104, Val 106, and Pro 107 were important amino acids for
      stimulating SVNF because substitutions at these positions diminished the
      reactivity of SVNF. However, we also found that substituting an Ala for a Val at
      position 100 or a Val for an Ala at position 110 enhanced reactivity of SVNF. We
      were able to further enhance the immunogenicity of this epitope by extending the
      carboxyl terminus two amino acids and making the resulting carboxyl-terminal Lys
      an amide and by adding a Glu to the amino terminus. These modifications shifted
      the in vitro activity of SVNF at least two orders of magnitude. We also compared
      the ability of this modified peptide and the wild-type SIV nef 96-112 to prime a
      T cell response in vivo. We primed mice with various doses of either the wild
      type or the modified peptide and looked at the ability of the draining lymph node
      cells to proliferate to wild-type peptide. We found that the modified peptide was
      10- to 100-fold better at priming a T cell response than the wild-type peptide.
      Therefore, we were able to create a peptide that was more immunogenic than the
      wild-type peptide in vivo as well as in vitro. Manipulations such as these that
      enhance the immunogenicity of T cell epitopes must be considered in developing
      peptide vaccines against HIV or other infectious agents.

PMID- 1378069
TI  - The effect of the Cmv-1 resistance gene, which is linked to the natural killer
      cell gene complex, is mediated by natural killer cells.
AB  - The resistance of mice to lethal infection by murine CMV (MCMV) is under complex
      host genetic control with contributions from both H-2 and non-H-2 genes. We have
      previously shown that an autosomal, non-MHC encoded gene, Cmv-1, controls MCMV
      replication in the spleen. We have investigated the mechanism by which the Cmv-1
      resistance gene confers protection against MCMV infection. Using H-2 compatible
      irradiation bone marrow chimeras, the enhanced resistance to MCMV infection that
      is associated with the Cmv-1l allele in the C57BL background was shown to be
      mediated by an irradiation-sensitive bone marrow-derived cell population, or a
      factor produced by these cells. The lack of correlation between serum IFN titers
      and the strain distribution pattern of Cmv-1 in CXB recombinant inbred mouse
      strains suggests that IFN does not mediate resistance conferred by this gene.
      Similarly, the lack of effect of in vivo depletion of mature CD4+ and CD8+ T
      cells on virus replication in C57BL/6J mice indicates that T cells are unlikely
      to be involved. In contrast, in vivo depletion of NK cells by injection of the
      anti-NK1.1 mAb PK136 abrogated restricted splenic virus replication in C57BL/6J--
      -BALB.B chimeric mice and in the Cmv-1l CXB strains. These data indicate that the
      effect of the Cmv-1 gene is mediated by NK cells. The significant augmentation in
      NK cell activity after MCMV infection of the susceptible Cmv-1h strains
      (BALB/cBy), CXBG/By, CXBH/By, CXBI/By, and CXBK/By) indicates the existence in
      these mice of NK cells that are functionally and phenotypically distinct from
      those in Cmv-1l strains. NK cells present in the Cmv-1h strains are unable to
      restrict efficiently splenic MCMV replication in vivo, possibly due to a lack of
      specificity for virus-infected target cells. Finally, flow cytometric analysis of
      NK1-1 expression in CXB and BXD RI mice together with MCMV replication studies in
      the BXD RI strains indicate that Cmv-1 is closely linked to NK1.1 and other loci
      that reside on a distal segment of murine chromosome 6 in a region that has
      recently been defined as the natural killer complex.

PMID- 1378070
TI  - Involvement of beta 2-integrins in the migration of human natural killer cells.
AB  - Human large granular lymphocytes with the NK cell phenotype (CD16+ or CD56+CD3-)
      were greatly enriched among the cells which migrated spontaneously through
      untreated or albumin-coated, 3-microns pore size polycarbonate filters for 1 to 8
      h. Three days of rIL-2 treatment (300 IU/ml) and 3 to 5 wk of rIL-2 treatment
      (100 IU/ml) generated a 2.7 +/- 0.9-fold and 5.6 +/- 0.8-fold increase in cell
      migration, respectively. The adhesion and subsequent migration of freshly
      isolated NK cells was mainly mediated by CD11b/CD18, because migration could be
      inhibited by 80 +/- 8% anti-CD11b (Mac-1) antibodies but not with antibodies
      against CD11a (LFA-1) or CD11c (p150,95), the other alpha-chains of the beta 2
      integrins. After rIL-2 activation, however, CD11a/CD18 was the major receptor
      utilized in migration, inasmuch as anti-CD11a antibody caused a 69 +/- 8%
      reduction in the number of migrated cells. Anti-CD11b antibody decreased
      migration by 43 +/- 12%, and together these antibodies inhibited migration by 82
      +/- 7%. Anti-CD11a alone did not have any effect on adhesion, but CD11a/CD18
      cooperated in the adhesion because anti-CD11b decreased adhesion by 40 +/- 11%
      and together these antibodies inhibited adhesion by 74 +/- 6%. The ability of
      large granular lymphocytes to rapidly utilize beta 2-integrins and unidentified
      ubiquitous ligands for binding and migration may be significant for their
      capacity to function in the first line of immune defense under highly variable
      conditions.

PMID- 1378072
TI  - Adherence of rat basophilic leukemia (RBL-2H3) cells to fibronectin-coated
      surfaces enhances secretion.
AB  - Rat basophilic leukemia (RBL-2H3) cells are a useful in vitro model for studies
      of mast cells and basophils. We examined the adherence of RBL-2H3 cells to
      different extracellular matrix proteins and the effect of such attachment on
      secretion. The cells bound to fibronectin-coated surfaces with maximum binding by
      1 h at 37 degrees C. There was less attachment to laminin, collagen type I, and
      collagen type IV. There was no adherence to uncoated surfaces or in the absence
      of Ca2+. Binding to fibronectin was blocked by a synthetic peptide containing the
      sequence Arg-Gly-Asp. Therefore, the binding of RBL-2H3 cells to fibronectin may
      be mediated by surface molecules that belong to the integrin family. Adherence to
      fibronectin-coated surfaces resulted in cell spreading, a reorganization of the
      cytoskeletal elements, and a redistribution of the secretory granules. Attachment
      to fibronectin also dramatically enhanced high affinity IgE receptor-mediated
      histamine release. This enhancement was maximum by 1 h of adherence and lasted
      for at least 6 h. There was also enhanced secretion by the Ca2+ ionophore A23187.
      Thus, adherence to fibronectin can enhance both receptor and non-receptor
      mediated release. Addition of soluble fibronectin to RBL-2H3 cells in suspension
      had no effect on secretion. Therefore, enhanced histamine release required cell
      attachment to immobilized fibronectin. These results suggest that secretion from
      mast cells/basophils may be modulated by their interaction with the extracellular
      matrix.

PMID- 1378071
TI  - The human recombinant c-kit receptor ligand, rhSCF, induces mediator release from
      human cutaneous mast cells and enhances IgE-dependent mediator release from both
      skin mast cells and peripheral blood basophils.
AB  - The gene product of the steel locus of the mouse represents a growth factor for
      murine mast cells and a ligand for the c-kit proto-oncogene receptor, a member of
      the tyrosine kinase receptor class of oncogenes (for review, see O. N. Witte.
      1990. Cell 63:5). We have studied the effect of the human recombinant c-kit
      receptor ligand stem cell factor (rhSCF) on the release of inflammatory mediators
      from human skin mast cells and peripheral blood basophils and compared its
      activity to that of rhIL-3, rhSCF (1 ng/ml to 1 microgram/ml) activated the
      release of histamine and PGD2 from mast cells isolated from human skin. Analysis
      by digital video microscopy indicated that purified human skin mast cells (84 +/-
      5% pure) responded to rhSCF (0.1 to 1 microgram/ml) challenge with a rapid,
      sustained rise in intracellular Ca2+ levels that was accompanied by secretion of
      histamine. A brief preincubation (10 min) of mast cells with rhSCF (0.1 pg/ml to
      1 ng/ml) significantly enhanced (100 +/- 35%) the release of histamine induced by
      anti-IgE (3 micrograms/ml), but was much less effective on IgE-mediated release
      of PGD2. In contrast, a short term incubation with rhSCF did not potentiate the
      secretion of histamine activated by substance P (5 microM). A 24-h incubation of
      mast cells with rhSCF did not affect the release of mediators induced by anti-IgE
      (3 micrograms/ml), probably due to receptor desensitization, rhSCF (1 ng/ml to 3
      micrograms/ml) neither caused release of histamine or leukotriene C4 (LTC4)
      release from leukocytes of 14 donors, nor induced a rise in intracellular Ca2+
      levels in purified (greater than 70%) basophils. Brief preincubation (10 min) of
      leukocytes with rhSCF (1 ng/ml to 3 micrograms/ml) caused an enhancement (69 +/-
      11%) of anti-IgE-induced release of histamine that was significant at
      concentrations as low as 3 ng/ml (p less than 0.05), whereas it appeared less
      effective in potentiating IgE-mediated LTC4 release. In contrast, a prolonged
      incubation (24 h) with rhSCF (0.1 pg/ml to 100 ng/ml) did not enhance the release
      of histamine or LTC4 induced by anti-IgE (0.1 microgram/ml), whereas rhIL-3 (3
      ng/ml) significantly potentiated the release of both mediators.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1378073
TI  - RANTES, a monocyte and T lymphocyte chemotactic cytokine releases histamine from
      human basophils.
AB  - Chemotaxis of different populations of cells and release of proinflammatory
      mediators in response to antigenic stimulation are important processes in
      allergic diseases. These lead to the late phase response, a hallmark of chronic
      allergic diseases. Recombinant RANTES, a member of the "intercrine/chemokine"
      family of cytokines, has been previously shown to be chemotactic for monocytes
      and T cells of memory/helper phenotype. In this manuscript, we show that it is
      capable of inducing histamine release from human basophils at concentrations as
      low as 10(-10) M and compare its activity with that of monocyte chemotactic and
      activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), another
      intercrine/chemokine. RANTES (10(-7) M) caused histamine release from the
      leukocytes of 26 of 33 donors tested (mean 21.8 +/- 3.1%). In the same group of
      donors, MCAF/MCP-1, goat anti-human IgE (anti-IgE; 1 microgram/ml), and FMLP (10(
      5) M) released 41.1 +/- 2.9%, 40.5 +/- 4.6%, and 44 +/- 3.1% histamine,
      respectively. The percent histamine release by RANTES in atopic vs nonatopics was
      30.3 +/- 6.7 and 16.5 +/- 2.4, respectively (p less than 0.05), and histamine
      release by RANTES correlated significantly with histamine release by MCAF (r =
      0.69; p less than 0.001) but not with histamine release by anti-IgE (r = 0.29; p
      greater than 0.05). Histamine release by RANTES and MCAF/MCP-1 was extremely
      rapid, reaching a maximum within 1 min. RANTES was also shown to activate highly
      purified basophils (80% pure), and its activity was inhibited by a polyclonal
      anti-RANTES antibody. At a suboptimal concentration (6 x 10(-9) M), RANTES did
      not prime basophils to enhance histamine release by secretagogues such as anti
      IgE, C5a, or FMLP. On the other hand, preincubation of basophils with RANTES or
      MCAF/MCP-1 desensitized basophils to either factor but not to anti-IgE, C5a, or
      FMLP. Preincubation of basophils with pertussis toxin markedly diminished the
      basophil response to either RANTES or MCAF/MCP-1. These results suggest that
      RANTES and MCAF/MCP-1: 1) are potent activators of basophils; 2) may function via
      the same, or a closely related, receptor system in basophils; and 3) may
      represent a link between activation of monocytes, lymphocytes, and basophils in
      inflammatory disorders such as the late phase allergic reaction.

PMID- 1378074
TI  - Two major groups of neutralizing anti-gp120 antibodies exist in HIV-infected
      individuals. Evidence for epitope diversity around the CD4 attachment site.
AB  - The aim of this study was to dissect neutralizing anti-gp120 antibody populations
      in seropositive asymptomatic individuals. Murine anti-Id mAb were raised against
      polyclonal affinity-purified human anti-gp120 antibodies. These anti-Id mAb were
      used to fractionate anti-gp120 antibodies from a pool of HIV-positive sera into
      idiotypically distinct anti-gp120 antibody (Id+Ab) preparations. Immunochemical
      and neutralization studies indicated that all Id+Ab that neutralized HIV-1 in
      vitro interacted with either the V3 loop or the CD4 attachment site of gp120. The
      V3-specific Id+Ab neutralized HIV-1 in a strain-restricted manner. Id+Ab specific
      for the CD4 attachment site exhibited different spectra of neutralizing
      activities against multiple strains of HIV-1. This finding indicates that
      multiple, antigenically diverse epitopes reside around the CD4 attachment site of
      gp120. Significantly, depletion of the Id+Ab from affinity-purified total anti
      gp120 antibodies abrogated most of the neutralizing activities of these
      antibodies, suggesting that neutralizing anti-gp120 antibodies consist of two
      major specificities, either to the V3 region or to the CD4 attachment site. The
      understanding of specificities and neutralizing activities of different anti
      gp120 antibodies in seropositive healthy individuals will be helpful for
      designing effective vaccines and immunotherapeutic strategies for AIDS.

PMID- 1378075
TI  - Soluble forms of CD40 inhibit biologic responses of human B cells.
AB  - We have expressed the CD40 surface Ag as both a soluble 28-kDa molecule and a 57
      kDa Fc fusion protein containing the human IgG1 Fc region. Soluble CD40 and the
      Fc fusion protein inhibited the proliferative response of anti-IgM-activated
      human B cells to the CD40 mAb G28-5. Similarly, G28-5- and IL-4-induced IgE
      secretion from PBMC depleted of T cells was effectively blocked by both forms of
      soluble CD40. Although the soluble constructs of CD40 had only a minimal
      inhibitory effect on IL-4-mediated proliferation of anti-IgM-activated B cells,
      IL-4-induced soluble CD23 shedding from both PBMC and T cells depleted of PBMC,
      and IgE secretion from PBMC, were significantly reduced in a concentration
      dependent manner when soluble CD40 was present in the culture. The data presented
      demonstrate that both soluble forms of the CD40 molecule are biologically active,
      and suggest that the ligand for CD40 is inducible in IL-4-stimulated cultures and
      that it mediates both shedding of sCD23 and IgE secretion.

PMID- 1378076
TI  - CD34+ bone marrow cells are infected with HIV in a subset of seropositive
      individuals.
AB  - Individuals infected with HIV frequently develop cytopenias and suppressed
      hematopoiesis. The role of direct HIV infection of hematopoietic progenitor cells
      in this process has not been defined. In this study, purified CD34+ bone marrow
      progenitor cells from 74 Zairian and American patients were studied by both
      coculture viral isolation and polymerase chain reaction for evidence of HIV
      infection. A total of 36.5% of Zairian and 14% of American patients had HIV
      infection of the CD34+ cell subset, with as many as 1 in 500 CD34+ cells
      infected. Most of the Zairian patients in this study had advanced HIV infection
      and markedly decreased CD4/CD8 T lymphocyte ratios (mean 0.160 +/- 0.08), and no
      laboratory value predicted the presence of infection in the CD34+ subset of a
      given Zairian individual. In contrast, American patients with CD34+ cell
      infection had total CD4 cells less than 20/mm3 and a greater decrease of the
      CD4/CD8 T lymphocyte ratio compared to seropositive Americans without CD34+ cell
      infection (p = 0.003). Hematopoiesis, studied by methylcellulose colony assays,
      was depressed in all seropositive patients studied with no significant further
      suppression when CD34+ cells were infected. Thus, CD34+ bone marrow progenitor
      cells are infected in vivo in a subset of seropositive individuals and may serve
      as an additional reservoir of virus in HIV-infected individuals.

PMID- 1378077
TI  - Regulation of vascular cell adhesion molecule 1 on human dermal microvascular
      endothelial cells.
AB  - Vascular endothelial cell adhesion molecule 1 (VCAM-1) is an adherence molecule
      that is induced on endothelial cells by cytokine stimulation and can mediate
      binding of lymphocytes or tumor cells to endothelium. Because these interactions
      often occur at the level of the microvasculature, we have examined the regulation
      of expression of VCAM-1 in human dermal microvascular endothelial cells (HDMEC)
      and compared it to the regulation of VCAM-1 in large vessel human umbilical vein
      endothelial cells (HUVEC). Both cell populations were judged pure as assessed by
      expression of von Willebrand factor and uptake of acetylated low density
      lipoprotein. Expression of VCAM-1 was not detectable on either unstimulated HDMEC
      or HUVEC when assessed by ELISA or flow cytometry. Stimulation of either HDMEC or
      HUVEC with TNF-alpha resulted in a time- and dose-dependent induction of VCAM-1.
      However, although TNF-alpha-induced cell surface and mRNA expression of VCAM-1 in
      HDMEC was transient, peaking after 16 h of stimulation, TNF stimulation led to
      persistently elevated cell surface expression of VCAM-1 on HUVEC. IL-1 alpha also
      induced cell surface expression of VCAM-1 on HUVEC in a time- and dose-dependent
      manner, but stimulation of HDMEC with IL-1 alpha at doses up to 1000 U/ml failed
      to induce significant cell surface expression. However, IL-1 alpha induced time-
      and dose-dependent increases in ICAM-1 on HDMEC. Similarly, IL-4 induced VCAM-1
      expression and augmented TNF-alpha-induced expression on HUVEC but did not affect
      VCAM-1 expression on HDMEC. Binding of Ramos cells to cytokine-stimulated
      endothelial cell monolayers correlated with VCAM-1 induction. Increased binding
      was seen after stimulation of HDMEC with TNF-alpha, which was blocked by anti
      VCAM-1 mAb, but no increases in binding were noted after stimulation of HDMEC
      monolayers with IL-1 alpha. These data provide additional evidence for the
      existence of endothelial cell heterogeneity and differences in cell adhesion
      molecule regulation on endothelial cells derived from different vascular beds.

PMID- 1378078
TI  - Drug-specific T cells derived from patients with drug-induced allergic hepatitis.
AB  - Drug-induced allergic hepatitis is a tissue-specific inflammatory disease caused
      by hypersensitivity to a particular drug. Although the frequency of drug-induced
      allergic hepatitis appears to increase in proportion to the medicine, the
      mechanism by which tissue specificity is determined is still to be elucidated. In
      this study, we established CD4+ T cell clones specific for particular drugs from
      patients with drug-induced allergic hepatitis accompanied with mild blood
      eosinophilia and analyzed the possible role of liver protein as a directing
      factor of liver-specific inflammatory reactions. All CD4+ T cell clones obtained
      from two patients with this disease proliferated in response to a combination of
      the particular drug plus liver specific protein (LSP), which consists of over 30
      proteins. Some T cell clones were responsive to an antigenic conformation
      consisting of the 200-kDa glycoprotein (partly purified LSP), a component of LSP,
      plus the causal drug. In contrast, all CD4+ T cell clones from a patient with
      simple drug-induced eosinophilia responded to the causal drug in the absence of
      LSP and partly purified LSP. These data suggested that LSP or partly purified LSP
      of the appropriate Ag is the target that leads to liver-specific inflammation in
      drug-induced allergic hepatitis. Furthermore, T cell lines derived from patients
      with drug-induced allergic hepatitis and simple drug-induced eosinophilia
      produced large amounts of IL-5 after the appropriate antigenic stimulation,
      whereas CD4+ T cell clones from donors with a normal amount of peripheral blood
      eosinophils secreted a much less IL-5. Taken together, these results indicate
      that overproduction of IL-5 by the allergen-sensitized T cells may result in
      blood eosinophilia.

PMID- 1378079
TI  - Use of human universally antigenic tetanus toxin T cell epitopes as carriers for
      human vaccination.
AB  - Synthetic constructs were assembled as multiple Ag peptide systems containing
      repetitive sequences of Plasmodium falciparum and Plasmodium berghei, the
      causative agents of human and murine malaria respectively, and two universal
      human tetanus toxin T cell epitopes 830-843 and 947-967. These constructs were
      tested for antibody production in mice and for their capacity to stimulate human
      PBL and tetanus toxin-specific T cell clones. A high antibody titer can be
      obtained in mice when multiple Ag peptide systems are injected in various
      adjuvants or in PBS alone. Furthermore, all constructs can activate PBL from
      every donor tested. However, a variable response was obtained when different
      clones specific for the two tetanus toxin universal epitopes were used. These
      constructs may represent possible candidates for a malaria vaccine.

PMID- 1378081
TI  - Therapeutic approaches to varicella-zoster virus infections.
AB  - Varicella-zoster virus (VZV) infections, the cause of chickenpox and shingles,
      are usually benign but are associated with morbidity and mortality, especially in
      immunocompromised hosts. Significant advances have been achieved in the treatment
      of VZV infections. In immunocompromised patients, both vidarabine and acyclovir
      have proved useful for the therapy of chickenpox and herpes zoster. Acyclovir,
      administered intravenously, is the treatment of choice for these infections. Both
      chickenpox and herpes zoster in the normal host are amenable to therapy with
      orally administered acyclovir. For older individuals with herpes zoster,
      acceleration of cutaneous healing can be accomplished at dosages of 800 mg five
      times a day for 10 days. Acyclovir therapy of chickenpox is recommended for
      adolescents and young adults with infection. In the future, improved therapies
      for VZV infections may include such newer antiviral drugs as bromovinyl
      arabinosyl uracil and acyclovir prodrugs.

PMID- 1378080
TI  - A novel cell-surface molecule expressed by human interdigitating reticulum cells,
      Langerhans cells, and activated lymphocytes is a new member of the Ig
      superfamily.
AB  - cDNA isolated from a human lymphocyte library were analyzed and shown to encode a
      novel cell-surface glycoprotein, termed HB15, expressed by dendritic cell subsets
      and activated lymphocytes. The predicted mature 186 amino acid protein was
      composed of a single extracellular V-type Ig-like domain, a transmembrane region,
      and a 39-amino acid cytoplasmic domain. In contrast to most Ig-like domains,
      analysis of a partial genomic DNA clone revealed that the extracellular Ig-like
      domain of HB15 was encoded by at least two exons. Northern blot analysis revealed
      that HB15 derived from three mRNA transcripts of approximately 1.7, 2.0, and 2.5
      kb expressed by lymphoblastoid cell lines. Two mAb reactive with HB15 were
      produced and used to show that HB15 is expressed as a single chain cell-surface
      glycoprotein of M(r) 45,000. HB15 expression was specific for lymphoblastoid cell
      lines and mitogen-activated lymphocytes, and HB15 was not expressed at detectable
      levels by circulating leukocytes. Immunohistologic analysis revealed that HB15
      had a unique pattern of expression, being found predominantly in hemopoietic
      tissues with strong expression by scattered interfollicular interdigitating
      reticulum cells and weak expression by germinal center cells. HB15 was also
      expressed by Langerhans cells within the skin. HB15 therefore serves as a unique
      marker for the subset of dendritic cells represented by Langerhans cells and
      interdigitating reticulum cells. Thus, the HB15 glycoprotein represents a newly
      identified member of the Ig superfamily that may play a significant role in Ag
      presentation or the cellular interactions that follow lymphocyte activation.

PMID- 1378082
TI  - Have we looked beyond the physical and psychosocial?
AB  - Palliative care can easily focus on physical and psychosocial problems but, for
      various reasons, ignore the spiritual needs of patients. There is confusion
      between the words 'religious' and 'spiritual,' the latter being the search for
      existential meaning, something done by all men and women--particularly as they
      approach death. This paper looks at excuses for not looking at spiritual issues
      but suggests the attending professional cannot avoid this aspect of care.

PMID- 1378083
TI  - Transfer of molecules from glia to axon in the squid may be mediated by glial
      vesicles.
AB  - Although the transfer of glial proteins into the squid giant axon is well
      documented, the mechanism of the transfer remains unknown. We examined the
      possibility that the transfer involved membrane-bound vesicles, by taking
      advantage of the fact that the fluorescent compound, 3,6-acridinediamine,
      N,N,N,',N'-tetramethylmonohydride [acridine orange (AO)], rapidly and selectively
      stains vesicular structures in glial cells surrounding the giant axon. We labeled
      cleaned axons (1-3 cm long) by incubation for 1 min in filtered seawater (FSW)
      containing AO. Because the AO was concentrated in glial vesicular organelles,
      these fluoresced bright orange when the axon was examined by epifluorescence
      microscopy. To look for vesicle transfer, axoplasm was extruded from such AO
      treated axons at various times after labeling. During the initial 15 min, an
      increasing number of fluorescent vesicles were observed. No further increases
      were observed between 15 and 60 min post AO. The transfer of the fluorescent
      vesicles into the axoplasm seemed to be energy dependent, as it was inhibited in
      axons treated with 2 mM KCN. These results suggest that a special mode of
      exchange exists between the adaxonal glia and the axon, perhaps involving
      phagocytosis by the axon of small portions of the glial cells.

PMID- 1378084
TI  - Differential effects of serotonin depletion on sensitization and dishabituation
      in the leech, Hirudo medicinalis.
AB  - The goal of these experiments was to test the hypothesis that serotonin (5-HT) is
      involved in facilitation of the shortening reflex in the leech Hirudo
      medicinalis. For this reason, we have used the toxin 5-hydroxytryptamine (5,7
      DHT) to deplete serotonin from the nervous systems of intact leeches and have
      assessed the effect on early facilitation, dishabituation, and sensitization of
      the touch-elicited shortening reflex using behavioral procedures previously
      developed in our lab (Boulis and Sahley, 1988). We find that 5,7-DHT lesions
      completely attenuate early facilitation and sensitization but only reduce
      dishabituation of the touch-elicited shortening reflex. Histological analyses of
      the ganglia from these leeches using glyoxilic acid staining procedures revealed
      an absence of staining in the Retzius cell of experimental leeches. All other
      serotonin-containing neurons showed glyoxilic acid staining comparable to that
      observed in the control leeches.

PMID- 1378085
TI  - Estradiol pulses induce progestin receptors selectively in substance P
      immunoreactive neurons in the ventrolateral hypothalamus of female guinea pigs.
AB  - Low doses of estradiol, administered as pulses, are as effective as higher doses
      for priming ovariectomized (OVX) guinea pigs to display progesterone-facilitated
      lordosis. High doses of estradiol, administered by constant-release implants,
      induce progestin receptors in many substance P-immunoreactive (SP-IR) neurons in
      the ventrolateral hypothalamus (VLH), a site at which estradiol primes OVX guinea
      pigs to respond behaviorally to progesterone. To test the hypothesis that
      behaviorally effective estradiol pulses induce progestin receptors selectively in
      substance P-containing neurons in the VLH, OVX females received estradiol
      implants 1 week prior to perfusion, or two pulses of estradiol-17 beta, injected
      39 and 11 h before perfusion. Colchicine was administered
      intracerebroventricularly prior to perfusion. No significant differences were
      observed in the total number of progestin receptor-immunoreactive (PR-IR) or
      substance P-immunoreactive cells in the VLH and VLH/ventromedial hypothalamus
      (VMH), respectively, of females receiving the two estradiol treatments. However,
      the percentage of PR-IR cells in the VLH also immunoreactive for SP was
      significantly higher in the estradiol pulse-treated (53%), than in the estradiol
      capsule-implanted animals (36%). These data suggest that behaviorally effective
      estradiol pulses induce progestin receptors selectively in substance P-containing
      neurons in the VLH and are consistent with the hypothesis that substance P is
      involved in progesterone-facilitated lordosis in guinea pigs.

PMID- 1378087
TI  - Inhibitory effects of flavonoids on Moloney murine leukemia virus reverse
      transcriptase activity.
AB  - Several flavonoids were tested for their effects on Moloney murine leukemia virus
      reverse transcriptase activity. Four groups of flavonoids, namely flavones,
      flavanones, flavonols, and flavanonols, were studied, and it was found that
      flavonols and flavanonols were very active in this regard while flavones and
      flavanones displayed very low activity. Among the flavonoids tested, fisetin,
      quercetin, myricetin, kaempferol, morin, (+/-)-taxifolin, (+)-catechin, and (-)
      epicatechin were shown to be highly effective in inhibiting the reverse
      transcriptase activity. Structure-activity relationship analysis of these
      flavonoids revealed that the simultaneous presence of free hydroxyl groups at
      positions 3 and 4' enhanced the reverse transcriptase inhibitory activity.
      Replacement of the 3-hydroxyl group with a monosaccharide or of the 4'-hydroxyl
      group with a methyl group reduced inhibitory activity. The double bond at
      position 2 and 3 of the flavonoid's pyrone ring is not essential for inhibiting
      reverse transcriptase activity. The flavonoids studied demonstrated ability to
      inhibit the reverse transcriptase activity using either (rA)n(dT)12-18 or
      (rC)n(dG)12-18 as template-primers.

PMID- 1378086
TI  - Progestin receptors in substance P-immunoreactive neurons in the hypothalamus of
      male guinea pigs after behaviorally effective estradiol pulse treatment.
AB  - Pulsatile administration of estradiol effectively primes orchidectomized (ORCH)
      male guinea pigs to display progesterone-facilitated lordosis. In contrast, a
      single injection of estradiol benzoate (EB) is not behaviorally effective. In
      ovariectomized female guinea pigs, estradiol pulses induce progestin receptors
      selectively in substance P neurons in the ventrolateral hypothalamus (VLH), a
      site at which estradiol primes females to respond behaviorally to progesterone.
      To test the hypothesis that behaviorally effective estradiol pulses induce
      progestin receptors selectively in substance P neurons in the VLH in males, ORCH
      animals received a single injection of EB 40 h before, or two pulses of estradiol
      17 beta, 39 and 11 h before perfusion. Colchicine was administered
      intracerebroventricularly prior to perfusion. The only difference found between
      the two estradiol treatment groups was a higher number of progestin receptor
      immunoreactive (PR-IR) cells in the rostral VLH of estradiol pulse-treated males.
      There were no significant differences in the number of PR-IR cells in the mid- or
      caudal VLH, nor in the number of substance P-immunoreactive (SP-IR) neurons in
      the VLH/ventromedial hypothalamus (VMH) of animals receiving the two estradiol
      treatments. Furthermore, the percentage of PR-IR cells in the VLH also
      immunoreactive for SP did not differ between the estradiol pulse- (22%-25%) and
      the EB-injected animals (22%-32%). These data do not support the hypothesis that
      administration of behaviorally effective estradiol pulses, as compared to
      behaviorally ineffective EB injections, induce progestin receptors selectively in
      substance P neurons in the VLH of male guinea pigs.

PMID- 1378089
TI  - Tumour necrosis factor causes an increase in axonal transport of protein and
      demyelination in the mouse optic nerve.
AB  - An increase in fast axonal transport of protein by the optic nerve was found in
      mice following a single combined injection of human recombinant tumour necrosis
      factor alpha (rTNF) and [3H]proline into the vitreous chamber. Demyelination was
      observed in optic nerve fibres arising from the eyes of mice which received a
      single rTNF injection. No such changes were detected when heat-inactivated rTNF
      was injected with the label. The effects of intravitreal injection of rTNF on the
      pathophysiology of mouse optic nerve resembled those found in mice infected with
      Semliki Forest virus (SFV), an animal model of multiple sclerosis. We suggest
      that TNF could mediate at least some of the pathophysiological changes found in
      SFV-infected mice and may provide a clue concerning the disease mechanism in
      multiple sclerosis.

PMID- 1378088
TI  - Reactivity of two anti-galactosyl ceramide antibodies towards myelin basic
      protein.
AB  - Two anti-galactosyl ceramide antibodies (polyclonal Ab142 and a monoclonal
      antibody) were characterized in terms of their reactivity towards purified lipids
      and myelin basic protein. Polyclonal Ab142 is a rabbit anti-mouse galactosyl
      ceramide (Gal C) IgG. Antigenic recognition is dependent on both galactose and
      ceramide since neither could inhibit galactosyl ceramide binding by more than
      10%. MAb-Gal C is a monoclonal antibody raised in mice against galactosyl
      ceramide. Binding of MAb-Gal C to Gal-C was equally inhibited by ceramide and
      galactose to approximately 50%, indicating that both groups are important for
      antibody recognition. MAb-Gal C was also shown to be reactive with the
      structurally related lipids, sphingomyelin and sulfatide. Polyclonal Ab142,
      although raised against Gal C, was shown to be 3-fold more reactive with
      component 8 (C-8) of myelin basic protein than Gal C. On the other hand, the MAb
      Gal C which also reacted with C-8 was 2-fold less reactive with C-8 than with Gal
      C. Neither of these antibodies were reactive with component 1 (C-1) of myelin
      basic protein. An anti-MBP IgG was shown to be reactive with C-1 and C-8 but
      unreactive with Gal C. In competitive inhibition ELISA, C-8 was able to compete
      out 44% and 41% of Gal C binding to polyclonal Ab142 and MAb, respectively. The
      reverse competition demonstrated that Gal C could inhibit 75% of C-8 binding to
      both antibodies. D-galactose was unable to inhibit C-8 binding to either
      antibody, whereas ceramide was as efficient as Gal C.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1378090
TI  - Highly sensitive enzyme-linked immunosorbent assay for marograstim (KW-2228), a
      mutant of human granulocyte colony-stimulating factor.
AB  - An enzyme-linked immunosorbent assay (ELISA) for marograstim (KW-2228) was
      established. This ELISA proved to be highly sensitive with the detection limit of
      0.01 ng/ml (about 0.5 fmol/ml) of KW-2228 and the assay range between 0.01 and 2
      ng/ml. When 0.02 to 2 ng/ml of KW-2228 added to human plasma was determined, the
      variation coefficiencies of intra-day and inter-day assays were 0.4 to 7.6% and
      5.2 to 15.8%, respectively, with good recoveries. These results indicate that
      this ELISA will be applicable to pharmacokinetic studies on KW-2228. With respect
      to the specificity, recombinant human granulocyte colony-stimulating factor (rhG
      CSF) produced in Escherichia coli as well as KW-2228 which does not have sugar
      chains in its structure showed slightly less immunoreactivity toward the antibody
      raised against KW-2228. The rhG-CSF produced in Chinese hamster ovary cells (CHO)
      having sugar chains showed the lower immunoreactivity. The antigenic domains of
      KW-2228 were evaluated using a number of variants of hG-CSF. The variants having
      different amino acids from KW-2228 in the 1st to 5th residue of the N-terminus
      showed almost equal immunoreactivities to KW-2228. The immunoreactivities of the
      variants lacking 7 to 18 amino acids of N-terminus were less than 50% of that of
      KW-2228. No immunoreactivity was observed for the variants deleted in the area of
      70th to 130th amino acids from the N-terminus. In addition, the immunoreactivity
      of a variant lacking the 10 amino acids from the C-terminus was 20% of that of KW
      2228.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378091
TI  - Purification and characterization of a mouse hepatocyte growth-stimulating factor
      from the liver of carbon tetrachloride-treated mice.
AB  - Mouse hepatocyte growth-stimulating factor (mHGSF), which increased markedly in
      the liver of carbon tetrachloride-treated mice, was purified 275,000-fold with
      21% yield from extracts of the injured liver. The purification involves ammonium
      sulfate precipitation and chromatography on Affi-Gel Blue, heparin-Sepharose, and
      S-Sepharose. The purified factor migrated as a major band of 76,000 daltons under
      nonreducing conditions and two bands of 62,000 and 31,000 daltons under reduced
      conditions. A dose-response of this growth factor for stimulation of
      deoxyribonucleic acid synthesis in cultured rat hepatocytes and its maximal
      effects were similar to those of human hepatocyte growth factor (hHGF), which we
      previously purified from the plasma of patients with fulminant hepatic failure
      (E. Gohda et al., J. Clin. Invest., 81, 414-419 (1988)). The effect of mHGSF was
      additive to the maximal effect of epidermal growth factor and was synergistic
      with that of insulin or acidic fibroblast growth factor, but was neither additive
      nor synergistic with the maximal effect of hHGF. mHGSF, like hHGF, was sensitive
      to heat and trypsin treatments and to reduction by dithiothreitol. This factor
      did not react with an anti-hHGF antiserum. These results indicate that mHGSF is a
      hHGF-like factor, but it is immunologically different from hHGF.

PMID- 1378092
TI  - Homologous desensitization of human platelet thromboxane A2/prostaglandin H2
      receptors.
AB  - Desensitization of platelet thromboxane (TX)A2/prostaglandin (PG)H2 receptors was
      induced by incubating platelet-rich plasma with the stable PGH2 analog 11 alpha,9
      alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U46619) (1 microM). Iloprost, a
      stable prostacyclin analog, was included in the incubation to prevent platelet
      activation. The TXA2 mimetic, [1S-1 alpha,2 beta(5Z), 3 alpha(1E,3S*), 4 alpha)]
      7-[3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo - [2.2.1]heptan-2-yl]
      5-heptenoic acid (I-BOP), was used to induce platelet aggregation, shape change
      and increases in intracellular free calcium. The EC50 values for I-BOP-induced
      rise in intracellular free calcium (control = 10.2 +/- 1.5 nM; desensitized =
      79.4 +/- 22.4 nM, n = 6, P less than .05), aggregation (control = 15.8 +/- 2.4
      nM; desensitized = 51.7 +/- 11.9 nM; P less than .05, n = 5) and shape change
      (control = 172 +/- 37 pM; desensitized = 350 +/- 60 pM; P less than .05, n = 7)
      were increased by the preincubation with U46619. Aggregation responses to
      thrombin and the calcium ionophore, ionomycin, were unaltered by the
      preincubation with U46619. Equilibrium binding studies at pH 7.4 revealed a
      decrease in the number of binding sites for the receptor antagonist 9,11
      dimethylmethano-11,12- methano-16(3-iodo-4-hydroxyphenyl)-13,14-dihydro-13-aza-15
      alpha beta-omega- tetranor-TXA2 [125I]PTA-OH) (control = 3246 +/- 509
      sites/platelet, desensitized = 2198 +/- 324 sites/platelet, n = 6, P less than
      .05) without a change in affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378093
TI  - Involvement of charybdotoxin-sensitive K+ channel in the relaxation of bovine
      tracheal smooth muscle by glyceryl trinitrate and sodium nitroprusside.
AB  - To elucidate the involvement of K+ channels in the smooth muscle relaxation by
      glyceryl trinitrate (GTN) and sodium nitroprusside (SNP), effects of several K+
      channel antagonists on the relaxant responses to GTN, SNP and 8-bromoguanosine
      3',5'-cyclic monophosphate (8-Br-cGMP) were studied in bovine tracheal smooth
      muscle. Although an antagonist of large conductance Ca(++)-activated K+ channel,
      charybdotoxin, produced no definite effect on the relaxation induced by GTN, SNP
      and atriopeptin in the rabbit aortic ring preparation, this antagonist inhibited
      the relaxation by GTN, SNP, atriopeptin and 8-Br-cGMP in the bovine tracheal
      smooth muscle. Methylene blue, a soluble guanylate cyclase inhibitor, also had an
      inhibitory effect on the relaxation by GTN and SNP. Both apamin, a small
      conductance Ca(++)-activated K+ channel antagonist, and glibenclamide, an ATP
      sensitive K+ channel antagonist, did not exhibit any inhibitory effect on the
      relaxant responses to GTN and SNP. GTN and SNP increased cGMP content. The
      increment was attenuated by methylene blue, whereas it was unaffected by
      charybdotoxin. These results indicate the involvement of large conductance Ca(++)
      activated K+ channel in the relaxation of bovine tracheal smooth muscle by GTN,
      SNP and 8-Br-cGMP. The activation of K+ channel by GTN and SNP is thought to
      occur via increases in cGMP content.

PMID- 1378094
TI  - A central nervous system action of nitric oxide in blood pressure regulation.
AB  - We had reported that the systemic administration of N omega-methyl-L-arginine (L
      NMA), a specific inhibitor of nitric oxide (NO) synthesis from L-arginine (ARG),
      raises arterial blood pressure (BP) while paradoxically enhancing central
      sympathetic outflow. Cervical spinal cord transection abolishes the increase in
      sympathetic outflow and attenuates the pressor effect of L-NMA. Thus, in addition
      to lowering BP by direct vasorelaxation, NO may also act in the central nervous
      system to reduce vascular sympathetic tone. To test this hypothesis we have
      injected L-NMA directly into the central nervous system in anesthetized rats.
      Intracisternally (i.c.), L-NMA elicited a small pressor response accompanied by a
      marked increase in sympathetic renal nerve activity (RNA). In contrast, the
      inactive stereoisomer N omega-methyl-D-arginine had neither pressor nor neural
      effects. The increases in RNA and BP elicited by i.c. L-NMA were abolished by
      spinal cord transection at C1 to C2 and by the i.v. administration of ARG. When
      administered i.c., ARG also abolished the increase in RNA elicited by i.v. L-NMA
      and significantly attenuated the pressor response. Thus, our findings indicate
      that L-NMA acts centrally by an ARG-reversible mechanism in the anesthetized rat
      to stimulate sympathetic nerve activity. Inasmuch as centrally synthesized NO has
      been postulated to play a second messenger and/or neurotransmitter role, our
      findings suggest that one such function would be the central regulation of
      sympathetic outflow and hence, BP.

PMID- 1378095
TI  - Spinal interactions between opioid and noradrenergic agonists in mice:
      multiplicativity involves delta and alpha-2 receptors.
AB  - The nature of the interaction between spinally administered opioid and alpha-2
      agonists was investigated using the substance P behavioral test in mice. Morphine
      and agonists which more selectively activate mu or delta opioid receptors were co
      administered intrathecally with direct and indirect acting adrenergic agonists
      norepinephrine, cocaine or clonidine and the behavioral responses to
      intrathecally coadministered substance P were evaluated. The ED50 values for
      agonists administered separately and concurrently were computed and drug
      interactions were evaluated using isobolographic analyses. After separate
      administration, all the opioid and adrenergic agonists inhibited the substance P
      induced behavioral responses. Upon coadministration of opioid and adrenergic
      agonists, a multiplicative interaction was observed between morphine or the delta
      agonist D-Pen2-D-Pen-5-enkephalin and the adrenergic agonists. Additive or
      antagonistic interactions were found between the mu agonist Tyr-D-Ala-NMe-Phe
      Gly(ol) and the same adrenergic agonists. The opioid antagonist naloxone and the
      alpha-2 adrenergic antagonist idazoxan were given as intrathecal pretreatments at
      doses chosen to shift the dose-response curves of their corresponding agonist
      (given alone) 4- to 10-fold to the right; this always resulted in a smaller, but
      significant (2- to 4-fold) shift in the dose-response curve of the other agonist
      given alone. Intrathecal pretreatment with naloxone or idazoxan altered some
      interactions between the opioids and clonidine. Although naloxone blocked
      completely the multiplicative interaction between morphine and clonidine,
      idazoxan did not. Both naloxone and idazoxan changed the antagonistic interaction
      between Tyr-D-Ala-NMe-Phe-Gly(ol) and clonidine to a multiplicative interaction.
      Neither antagonist blocked the multiplicative interaction between D-Pen2-D-Pen5
      enkephalin and clonidine. These results suggest that: 1) interactions between
      opioid and adrenergic agonists in mouse spinal cord are mediated by delta and
      alpha-2 receptor subtypes; 2) the synergistic interaction between morphine and
      alpha-2 adrenergic agonists may involve action at delta opioid receptors; and 3)
      antagonist action on these drug interactions is complex.

PMID- 1378097
TI  - Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway
      constriction and airway edema induced by neurokinins and sensory nerve
      stimulation in guinea pigs.
AB  - FK224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2- penthylphenyl)
      propionyl]-L-threonyl]tyrosyl]-L-leucynyl]-D- phenylalanyl]-L-allo-threonyl]-L
      asparaginyl]-L-serine-nu-lactone) is a novel neurokinin (NK) antagonist that
      exhibits selectivity for NK1 and NK2 receptors. The effects of FK224 on airway
      constriction and airway edema induced by NKs and nerve stimulation have been
      investigated in guinea pigs. FK224 inhibited the contraction of isolated guinea
      pig trachea induced by substance P (SP, 10(-8) M), NKA (10(-9) M) and NKB (10(-8)
      M) in a concentration-dependent manner, and the IC50 values were 2.6 x 10(-6),
      1.3 x 10(-6) and 2.3 x 10(-7) M, respectively. Tracheal contraction induced by
      histamine and acetylcholine was not affected by FK224, suggesting a specific
      effect on NK-mediated responses. FK224 also inhibited the atropine-resistant
      contraction of isolated guinea pig bronchi induced by electrical field
      stimulation with an IC50 value of 3.5 x 10(-6) M. In in vivo experiments, FK224
      given i.v. inhibited SP (13.5 micrograms kg-1)-, NKA (1.1 micrograms kg-1)- and
      capsaicin (3.1 micrograms kg-1)-induced airway constriction in guinea pigs with
      ED50 values of 0.39 mg kg-1, 0.36 mg kg-1 and 1.1 mg kg-1, respectively. FK224
      also inhibited SP (1.3 micrograms kg-1)-, NKA (11 micrograms kg-1)- and capsaicin
      (100 micrograms kg-1)-induced airway edema with ED50 values of 0.14 mg kg-1, 0.29
      mg kg-1 and 0.30 mg kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378096
TI  - FK 224, a novel cyclopeptide substance P antagonist with NK1 and NK2 receptor
      selectivity.
AB  - We have discovered a novel cyclopeptide substance P (SP) antagonist, FK 224 (N
      [N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L
      threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L-allo- threonyl]-L-asparaginyl]-L
      serine-nu-lactone), which inhibited [3H]SP binding to guinea pig lung membranes
      in a dose-dependent manner. According to Rosenthal analysis, the inhibitory
      effect of FK 224 on [3H]SP binding appears to be competitive. In order to clarify
      the receptor subtype selectivity of FK 224, we have studied the interaction of FK
      224 with three tachykinin receptors (NK1, NK2 and NK3) by using receptor binding
      techniques and in vitro bioassays, and have also compared FK 224 with the novel
      nonpeptide antagonist, (+/-)-CP-96,345. In binding experiments, FK 224 dose
      dependently inhibited [3H]SP binding to rat cerebral cortical membranes (NK1) and
      [3H]neurokinin (NK) A (NKA) binding to rat duodenum smooth muscle membranes
      (NK2), but did not affect [3H]eledoisin binding to rat cerebral cortical
      membranes (NK3). In bioassay experiments, FK 224 inhibited SP-induced contraction
      of guinea pig ileum (NK1) and NKA-induced contraction of rat vas deferens (NK2)
      in a dose-dependent manner, but did not affect NKB-induced contraction of rat
      portal vein (NK3). In contrast, (+/-)-CP-96,345 inhibited SP-induced contraction
      of guinea pig ileum, but not NKA-induced contraction of rat vas deferens or NKB
      induced contraction of rat portal vein. In the presence of FK 224, SP dose
      response curves and NKA dose-response curves were shifted to the right in
      parallel with no depression of the maximal contraction.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1378098
TI  - Comparative assessment of poly-L-aspartic and poly-L-glutamic acids as
      protectants against gentamicin-induced renal lysosomal phospholipidosis,
      phospholipiduria and cell proliferation in rats.
AB  - Coadministration of poly-L-aspartic acid (poly-L-Asp) protects rats against all
      measured signs of aminoglycoside nephrotoxicity. Based on in vitro and acute in
      vivo models, previously we hypothesized that poly-L-Asp protects by forming
      complexes with the drug in lysomes of proximal tubular cells. However, another
      closely related peptide, poly-L-glutamic acid (poly-L-Glu), could not protect
      against gentamicin-induced phospholipidosis and nephrotoxicity, presumably
      because it is susceptible to rapid hydrolysis in sysosomes in vivo. The present
      study expands the in vivo comparison between these two polyanions to a subacute
      model of rats and examines in detail the influence of these polymers on the
      qualitative and quantitative morphological alterations of lysosomes,
      phospholipiduria and proliferation of cortical cells induced by gentamicin. Our
      results not only demonstrated that despite a significantly higher drug cortical
      accumulation, the coadministration of poly-L-Asp almost completely protects
      against the development of all these early renal alteration but also pointed to
      the possibility of a mild, albeit apparently nonlethal, lysosomal thesaurismosis
      to develop under these conditions. In contrast, poly-L-Glu could not protect
      against these early renal alterations, though cortical drug accumulation was not
      significantly higher; however, it induced a conspicuous proliferation of
      peritubular interstitial cells. Therefore, the present work, taken together with
      the earlier results of ours as well as that of others, tends to strengthen the
      hypothesis that the site of action of poly-L-Asp must be in lysosomes, which are
      also the organelles that sequester and accumulate the drug.

PMID- 1378099
TI  - In vivo and in vitro effects of the azidothymidine analog dideoxyinosine on the
      exocrine pancreas of the rat.
AB  - Phase I clinical trials of the purine analog 2',3'-dideoxyinosine (ddl) revealed
      that 10% of the patients developed pancreatitis, yet there was no clear
      relationship between increasing doses of ddl and the development of pancreatitis.
      To test the effects of chronic ddl administration on the structure and function
      of the rat pancreas, male Wistar rats were given ddl at 100 mg/kg/day i.p. for 35
      days or 1400 mg/kg/day for 30 days, in two divided doses. Serum amylase levels,
      pancreatic tissue water content (edema) and pancreatic morphology by light and
      electron microscopic examination of pancreata from ddl-treated rats were similar
      to those of rats receiving saline injections only (controls). 2',3'
      Dideoxyinosine administration did not alter the subcellular distribution of the
      lysosomal enzyme cathepsin B, whose redistribution to a more dense zymogen
      granule-enriched subcellular fraction is an early indicator of acute
      pancreatitis. Dispersed pancreatic acini from rats receiving ddl (100 mg/kg/day
      for 30 days) were incubated in vitro for 15 min with either caerulein or
      carbamylcholine as secretory stimuli. There was no detectable difference in the
      stimulatable amylase secretion from ddl-treated animals compared to the control
      group. Based on these findings, we conclude that ddl has no direct toxic effect
      on the rat pancreas. 2',3'-Dideoxyinosine may be contributing to pancreatitis in
      acquired immunodeficiency syndrome patients by potentiating other pancreatotoxic
      agents or by its action on a pancreas that is already altered by the human
      immunodeficiency virus infection.

PMID- 1378100
TI  - GABA-gated anion channels in intact crayfish opener muscle fibres and stretch
      receptor neurons are neither activated nor desensitized by glutamate.
AB  - The influence of glutamate on the GABA-activated Cl- conductance was studied in
      the slowly adapting stretch-receptor neuron and dactylopodite opener muscle fibre
      of the crayfish (Astacus astacus) using a two-microelectrode and a three
      microelectrode voltage clamp, respectively. Glutamate (0.5-1.0 mM) had no effect
      on the GABA-activated conductance in either preparation. This indicates that the
      availability of the inhibitory channels for activation of GABA is not influenced
      by glutamate. The present results are in sharp contrast to those obtained by
      Franke et al. (J Comp Physiol A 159:591-609, 1986) in experiments on excised
      membrane patches, which suggested that glutamate is capable of both activating
      and desensitizing inhibitory postsynaptic channels in the crayfish opener muscle
      fibre.

PMID- 1378101
TI  - Toad bladder amiloride-sensitive channels reconstituted into planar lipid
      bilayers.
AB  - In the present study we used established methods to obtain apical membrane
      vesicles from the toad urinary bladder and incorporated these membrane fragments
      to solvent-free planar lipid bilayer membranes. This resulted in the appearance
      of a macroscopic conductance highly sensitive to the diuretic amiloride added to
      the cis side. The blockage is voltage dependent and well described by a model
      which assumes that the drug binds to sites in the channel lumen. This binding
      site is localized at about 15% of the electric field across the membrane. The
      apparent inhibition constant (K(0)) is equal to 0.98 microM. Ca2+, in the
      micromolar range on the cis side, is a potent blocker of this conductance. The
      effect of the divalent has a complex voltage dependence and is modulated by pH.
      At the unitary level we have found two distinct amiloride-blockable channels with
      conductances of 160 pS (more frequent) and 120 pS. In the absence of the drug the
      mean open time is around 0.5 sec for both channels and is not dependent on
      voltage. The channels are cation selective (PNa/PCl = 15) and poorly discriminate
      between Na+ and K+ (PNa/PK = 2). Amiloride decreases the lifetime in the open
      state of both channels and also the conductance of the 160-pS channel.

PMID- 1378103
TI  - Staining sections of water-miscible resins. 2. Effects of staining-reagent
      lipophilicity on the staining of glycol-methacrylate-embedded tissues.
AB  - Glycol methacrylate (GMA) sections of animal tissues were stained with a group of
      twenty-seven reagents of very varied chemical characteristics. The artefactual
      background staining of the resin was found to be dependent on the
      hydrophilic/lipophilic character of the staining reagent, as estimated from the
      logarithm of its octanol-water partition coefficient (log P). Intense background
      staining occurred with lipophilic stains, whose log P greater than 2. In keeping
      with this, use of GMA semi-permeable membranes for enzyme histochemistry failed
      to give staining when using a lipophilic substrate, probably because the
      substrate was trapped in the membrane. An analysis of other routine histochemical
      stains--in terms of the probable occurrence of high resin background staining and
      low tissue sensitivity--is made. A numerical guide is provided to help avoid
      artefacts resulting from hydrophobic and size effects. Note: small, hydrophilic
      reagents (log P less than 0; molecular weight less than 550 Da) are least likely
      to show either type of artefact. Conversely, reagents which are lipophilic,
      or/and of intermediate size (log P greater than 2; 550 less than ionic weight
      less than 1000 Da), give strong background staining.

PMID- 1378102
TI  - Multiple-channel conductance states and voltage regulation of embryonic chick
      cardiac gap junctions.
AB  - We used the double whole-cell voltage-clamp technique on ventricle cell pairs
      isolated from 7-day chick heart to measure the conductance of their gap junctions
      (Gj) and junctional channels (gamma j) with a steady-state voltage difference
      (Vj) applied across the junction. Currents were recorded from single gap junction
      channels (ij) as symmetrical rectangular signals of equal size and opposite sign
      in the two cells, and gamma j was measured from ij/Vj. We observed channel
      openings at six reproducible conductance levels with means of 42.6, 80.7, 119.6,
      157.7, 200.4 and 240.3 pS. More than half of all openings were to the 80- and 160
      pS conductance levels. The probability that a high conductance event (e.g., 160
      or 240 pS) results from the random simultaneous opening of several 40-pS channels
      is small, based on their frequency of occurrence and on the prevalence of shifts
      between small and large conductance states with no intervening 40-pS steps. Our
      results are consistent with three models of embryonic cardiac gap junction
      channel configuration: a homogeneous population of 40-pS channels that can open
      cooperatively in groups of up to six; a single population of large channels with
      a maximal conductance near 240 pS and five smaller substates; or several
      different channel types, each with its own conductance. Gj was determined from
      the junctional current (Ij) elicited by rectangular pulses of applied
      transjunctional voltage as Ij/Vj. It was highest near 0 Vj and was progressively
      reduced by application of Vj between 20 and 80 mV or -20 and -80 mV. In response
      to increases in Vj, Gj decayed in a voltage- and time-dependent fashion. After a
      6-sec holding period at 0 Vj, the initial conductance (G(init) measured
      immediately after the onset of an 80-mV step in Vj was nearly the same as that
      measured by a 10-mV prepulse. However, during 6-sec pulses of Vj greater than +/-
      20 mV, Gj declined over several seconds from G(init)to a steady-state value
      (Gss). At potentials greater than +/- 20 mV the current decay could be fit with
      biexponential curves with the slow decay time constant (tau 2) 5-20 times longer
      than tau 1. For the response to a step to 80 mV Vj, for example, tau 1 = 127 msec
      and tau 2 = 2.6 sec. The rate of current decay in response to smaller positive or
      negative steps in Vj was slower, the magnitude of the decline was smaller, and
      the ratio tau 2/tau 1 decreased.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1378105
TI  - Differential distribution of tenascin and cellular fibronectins in acute and
      chronic renal allograft rejection.
AB  - BACKGROUND: Acute and chronic renal allograft rejection injuries involve, albeit
      variably, all compartments of the organ and are associated with significant
      structural changes. We hoped to gain new insights into these phenomena by
      determining distribution of certain extracellular matrix proteins known to be
      involved in architectural remodeling processes. EXPERIMENTAL DESIGN: Frozen
      tissue samples from biopsies of acute (n = 14) and chronic (n = 12) human renal
      allograft rejections were studied to compare distribution of tenascin, the
      extradomains A and B (EDA, EDB), and oncofetal (Onc) isoforms of cellular
      fibronectin (cFn). Normal kidneys (n = 4) served as controls. Cryosections were
      immunostained by the avidin-biotin-complex method with monoclonal antibodies
      specific for those molecules. RESULTS: In acute rejection, reactivity for
      tenascin and EDA-cFn was increased slightly to moderately in glomerular mesangia
      and in most vessels while it was intensely and diffusely increased in the
      interstitium. Rarely were focal EDB-cFn and Onc-cFn reactions seen in lesions
      deemed to reflect acute injury. In chronic rejection, tenascin and EDA-cFn were
      strongly increased in most glomerular mesangia and in vascular walls but unevenly
      in the interstitium. In rare glomerular synechiae and vessels, enhanced staining
      for tenascin and EDA-cFn as well as EDB-cFn and Onc-cFn was noted while in
      obsolete glomeruli only EDB-cFn and Onc-cFn were detected. The enhanced
      distribution of tenascin and EDA-cFn partly reflected that noted during
      nephrogenesis, whereas staining patterns for EDB-cFn and Onc-cFn differed from
      their fetal counterparts. CONCLUSIONS: Tenascin and EDA-cFn are strongly and
      preferentially expressed in the interstitial and vascular compartments of acute
      and chronic renal rejection injury suggesting that, in these sites, active repair
      and remodeling occur during both phases of the rejection process irrespective of
      the changes seen by conventional microscopy. Tenascin, EDA-cFn as well as EDB-cFn
      and Onc-cFn are all involved, albeit variably, in the glomerular and vascular
      alterations of chronic rejection. The finding of tenascin and of the three
      isoforms of cFn in glomerular synechiae with actively proliferating epithelium
      suggests that certain epithelial cells might partake in the synthesis of these
      molecules.

PMID- 1378106
TI  - Comparison of enoximone and piroximone in patients after mitral valve operation:
      a prospective and controlled clinical study.
AB  - Phosphodiesterase III (PDEII) inhibitors as so-called inodilators have previously
      proven a valuable alternative to positive inotropes in patients with cardiac
      insufficiency. In this study we compared patients receiving piroximone (P, n =
      14, 0.5-mg/kg bolus in 30 min and then 3-6 micrograms/kg/min) with enoximone
      patients (E, n = 13, 1-mg/kg bolus and then 4-20 micrograms/kg/min) and with a
      third group (D, n = 14) receiving a combination of dopamine (4-10
      micrograms/kg/min) and glyceroltrinitrate (0.5-5 micrograms/kg/min) for
      hemodynamic support. All three groups were comparable in terms of age, body
      surface area, and preoperative cardiac function [cardiac index (CI) less than or
      equal to 2.5 L/min/m2, LAP greater than 15 mm Hg]. Hemodynamic measurements (10)
      and Holter monitoring were performed until 18 h post MVR. In all groups,
      epinephrine was used for additional inotropic therapy if mean arterial pressure
      (MAP) was less than 60 mm Hg and/or CI was less than 2.5 L/min/m2. There was no
      early or late postoperative mortality in either group. Continuous support with
      epinephrine was necessary in 8 patients in group D, whereas initially 8 patients
      in group E and 6 patients in group P required epinephrine support. After PDE III
      inhibitor infusion, 2 patients in group E and 2 patients in group P remained
      epinephrine dependent (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378104
TI  - Activation of protein kinase C pathway contributes to hydrogen peroxide-induced
      increase in endothelial permeability.
AB  - BACKGROUND: We examined the effects of hydrogen peroxide (H2O2) on endothelial
      permeability and the possible role of protein kinase C (PKC) activation in
      mediating the response. EXPERIMENTAL DESIGN: Pulmonary microvessel endothelial
      cell monolayers were grown to confluency on gelatin- and fibronectin-coated
      microporous filters. Endothelial permeability was measured by determining the
      transendothelial clearance rate of [125I]albumin. The monolayers in all cases
      were challenged for 1 hour with H2O2. In some experiments, the monolayers were
      preincubated with PKC inhibitors H7 (an isoquinolinylsulphonamide derivative)
      (0.05 mM) or calphostin C (5 x 10(-6) mM) or with the inactive
      isoquinolinylsulphonamide analog, HA1004 (0.05 mM), before the H2O2 challenge.
      RESULTS: Addition of H2O2 (0 to 0.5 mM) to endothelial monolayers in the absence
      of PKC inhibitors resulted in a concentration-dependent increases in endothelial
      permeability and the response occurred without LDH release and morphologic
      evidence of cytolysis. The increase in permeability was significantly reduced by
      H7 and calphostin C, but not by HA1007. Immunocytochemical localization of PKC
      indicated that PKC isotype II was abundant in these cells and that it was
      distributed uniformly in the cytosol. H2O2 induced translocation of PKC to the
      cell membrane indicating enzyme activation. H7 and calphostin C prevented the
      H2O2-induced PKC translocation, whereas HA1004 had no effect. Both PKC inhibitors
      also prevented cell "rounding" and formation of interendothelial gaps, whereas
      HA1004 was ineffective. CONCLUSIONS: The results indicate that PKC activation is
      an important determinant of the H2O2-induced increase in endothelial
      permeability.

PMID- 1378107
TI  - Comparative electrophysiologic effects of metabolites of quinidine and
      hydroquinidine.
AB  - To evaluate whether the hydroxylated metabolites of quinidine (Q) and
      hydroquinidine (HQ): hydroxy-3S-quinidine (OH-Q) and hydroxy-3S-hydroquinidine
      (OH-HQ), exert electrophysiologic effects and participate in the therapeutic
      action of the parent drugs, we examined and compared the effects of the
      metabolites and the parent drugs on the electrical activity of guinea pig
      ventricular cells recorded by standard microelectrode technique. In addition, we
      investigated the potential arrhythmogenic properties of these compounds in rabbit
      Purkinje fibers in low K+ (2.7 mM) Tyrode's solution. The concentration [C]-,
      frequency-, and voltage-dependent effects of the drugs were investigated. Maximum
      upstroke velocity of phase 0 (Vmax) was [C]-dependently depressed by both OH-Q
      and OH-HQ but at a lesser degree than with Q and HQ, respectively: at the [C] of
      50 microM, Vmax depression attained 26.7 +/- 2.6% with OH-Q versus 45.9 +/- 1.6%
      with Q and 32.3 +/- 1.9% with OH-HQ versus 54.6 +/- 1.4% with HQ. This effect was
      frequency and voltage dependent without significant differences between the four
      compounds. In the presence of equipotent [C], recovery kinetics of Vmax was
      significantly slower with metabolites than with respective parent drugs. In
      contrast, the effects of metabolites on action potential duration at 90% of
      repolarization (APD90) and effective refractory period (ERP) differed from those
      observed with parent drugs. With metabolites, APD90 and ERP were increased in a
      [C]-dependent manner, whereas the Q- and HQ-induced lengthening in APD90 and ERP
      was observed only at low concentration and low frequency. In addition, the OH-Q-
      and OH-HQ-induced APD90 lengthening was not altered by increasing pacing rate. In
      rabbit Purkinje fibers, increase in cycle length and prolonged exposure to either
      metabolites or parent drug caused early afterdepolarizations (EADs) and triggered
      activity. With all drugs tested, EADs arose more frequently at the plateau level
      than at the final repolarization of AP, but the incidence of EADs appeared to be
      much lower with metabolites than with parent drugs. The present results
      demonstrate that OH-Q and OH-HQ exert qualitatively similar but quantitatively
      less potent depressant effects on Vmax than Q and HQ, respectively, but differ in
      the lengthening effect on APD. We suggest that metabolites may participate in
      class I antiarrhythmic action of their respective parent drug and contribute to
      their arrhythmogenicity.

PMID- 1378108
TI  - Effects of captopril on metabolic and hemodynamic alterations in global ischemia
      and reperfusion in the isolated working rat heart.
AB  - In the isolated working rat heart model, we studied metabolic and hemodynamic
      effects of 5- and 30-min global ischemia followed by reperfusion and assessed the
      potentially beneficial effect of captopril 80 micrograms/ml added throughout the
      experiment. Creatine kinase (CK) and catecholamines were measured in coronary
      effluent. De novo eicosanoids (prostaglandin E2) synthesis was assessed in
      endocardial explants. Hemodynamic alterations occurred after 30-min ischemia and
      were reflected most dramatically by a reduction in cardiac output (CO 72 +/- 10%
      of baseline values in captopril vs. 68 +/- 16% in controls) without significant
      differences as a result of treatment. Captopril shortened reperfusion ventricular
      fibrillation (VF) duration (6.9 +/- 1.2 vs. 13.6 +/- 8.7 min, p less than 0.05)
      but had no effect on VF incidence. No differences occurred in norepinephrine (NE)
      outflow, whereas total CK release was greater in controls. Five controls versus
      none of the treated hearts (p less than 0.05) released trace amounts of
      epinephrine during reperfusion. Increased de novo PGE2 synthesis was demonstrated
      after 5-min I (465 +/- 168 vs. 238 +/- 75 pg/100 mg tissue per hour, p less than
      0.01). Captopril stimulated production of PGE2 in normoxic hearts (p less than
      0.02), but the difference was no more apparent in ischemic hearts. We conclude
      that captopril produces some biochemical and electrophysiologic evidence of
      myocardial salvage, but these effects are not sufficient to induce hemodynamic
      improvement after global ischemia and reperfusion.

PMID- 1378109
TI  - Importance of the flow perfusion deficit in the response to captopril in
      experimental myocardial infarction.
AB  - Previous results on the effects of angiotensin-converting enzyme (ACE) inhibition
      in myocardial ischemia are conflicting. To determine whether acute ACE inhibition
      may influence myocardial perfusion deficit during ischemia and reduce ischemia
      reperfusion injury, anesthetized open-chest dogs underwent 2-h left anterior
      descending coronary artery (LAD) occlusion followed by 6-h reperfusion. After 1-h
      coronary occlusion, each dog was randomized to receive either captopril [5 mg/kg
      intravenous (i.v.) bolus and 0.25/kg/h infusion for 7 h] or saline. Whereas
      arterial pressure was reduced (p = 0.001), captopril did not influence myocardial
      perfusion deficit: Blood flow in the central ischemic zone represented 17.1 +/-
      2.8% of the flow in the nonischemic zone versus 20.5 +/- 3.8% before treatment
      (NS). The values of the control group were 17.8 +/- 2.5 and 16.7 +/- 2.4%,
      respectively. In addition, there was no difference in infarct size: 35.9 +/- 3.3%
      of the area at risk in captopril-treated dogs versus 40.0 +/- 3.6% in controls.
      Analysis of subgroups based on the level of the collateral flow indicated,
      however, that ACE inhibition had an adverse effect on infarct size in dogs with
      high collateral flow: 31.9 +/- 4.6% in captopril dogs versus 17.6 +/- 4.7 (p =
      0.048). This effect was related to a decrease in collateral flow because animals
      exhibiting the highest increase in perfusion deficit presented the greatest
      increase in infarct size (r = -0.92, p = 0.003). Although in dogs with low
      collateral flow, ACE inhibition appeared to exert a slight beneficial effect on
      infarct size, we conclude that at least in this dog model, acute ACE inhibition
      could exacerbate myocardial injury.

PMID- 1378110
TI  - Antioxidant effects of angiotensin-converting enzyme (ACE) inhibitors: free
      radical and oxidant scavenging are sulfhydryl dependent, but lipid peroxidation
      is inhibited by both sulfhydryl- and nonsulfhydryl-containing ACE inhibitors.
AB  - With an assay that generates free radicals (FR) through photooxidation of
      dianisidine sensitized by riboflavin, 4 x 10(-5) M captopril, epicaptopril (SQ
      14,534, captopril's stereoisomer), zofenopril, and fentiapril [all sulfhydryl (
      SH)-containing angiotensin-converting enzyme (ACE) inhibitors] were shown
      effective scavengers of nonsuperoxide free radicals whereas non-SH ACE inhibitors
      were not. Captopril was a more effective FR scavenger at pH 5.0 than at pH 7.5.
      Captopril (2 x 10(-5) M) also scavenged the other toxic oxygen species hydrogen
      peroxide and singlet oxygen and inhibited microsomal lipid peroxidation. Finally,
      captopril reduced the amount of superoxide anion-radical detected after
      neutrophils in whole blood were activated with zymosan, probably by inhibiting
      leukocyte superoxide production.

PMID- 1378111
TI  - Mechanism of antiarrhythmic efficacy of propafenone as assessed by programmed
      electrical stimulation in conscious dogs.
AB  - Programmed electrical stimulation (PES) was performed in 18 conscious,
      chronically instrumented mongrel dogs 6-21 days after a 4-h occlusion of the left
      anterior descending coronary artery (LAD). At baseline, 8 of 10 animals responded
      with sustained ventricular tachycardia (SVT) and 2 of 10 responded with
      ventricular fibrillation (VF). Cumulative administration of 2 and 4 mg/kg
      propafenone intravenously (i.v.) prevented induction of the baseline arrhythmia
      in 7 of 10 (p less than 0.05) and 5 of 10 (p = 0.1) animals, respectively.
      Cumulative administration of two doses of saline to 8 control animals with SVT
      inducible at baseline did not affect subsequent inducibility. QRS duration was
      only slightly prolonged after 2 mg/kg propafenone (+3.5 +/- 1.1 ms, p less than
      0.05). Administration of 4 mg/kg was associated with a further increase in QRS
      duration (+8.0 +/- 2.3 ms, p less than 0.01) and a decrease in sinus cycle length
      (-60.0 +/- 17.2 ms, p less than 0.05). Propafenone consistently and significantly
      prolonged ventricular refractoriness only in responders. Furthermore, at both
      dosages, there was a negative correlation between drug-induced increases in
      ventricular refractoriness and baseline refractoriness (r = -0.72, p = 0.02; r = 
      0.81, p = 0.005 with 2 mg/kg and 4 mg/kg propafenone, respectively). Thus, the
      lesser antiarrhythmic efficacy of 4 mg/kg as compared with 2 mg/kg may result
      from excessive increases in intraventricular conduction time and/or unfavorable
      hemodynamic effects of this dose. Furthermore, our study confirms an association
      of the antiarrhythmic efficacy of propafenone with increases in ventricular
      refractoriness. In addition, the present investigation demonstrated that such
      increases in refractoriness are most likely to occur at short baseline values.

PMID- 1378112
TI  - New sustained-release nifedipine formulation in treatment of essential
      hypertension. Unidipin Cooperative Study Group.
AB  - Sustained-release nifedipine (SR) (developed by Elan, Athlone, Ireland; Unidipin
      is the tradename of Nifedipine SR, registered by Farmitalia Carlo Erba SpA,
      Milano, Italy) is a new nifedipine formulation suitable for once-daily
      administration. In a double-blind, randomized study of 269 hypertensive subjects,
      nifedipine SR efficacy and tolerability were investigated in comparison with the
      conventional twice-daily nifedipine tablet formulation. After a 3-week placebo
      phase, patients were titrated to 50-100 mg once daily nifedipine SR or 20-40 mg
      twice daily (b.i.d.) of the reference treatment. Significant and comparable
      reductions in systolic and diastolic blood pressures (SBP, DBP) during supine
      rest and on standing were observed in the two groups during and at the end of 3
      month treatment. At the last visit, supine BP reductions of 17 +/- 17.7/14.8 +/-
      8.8 mm Hg 24 h after nifedipine SR and of 21.7 +/- 19/16.1 +/- 9 mm Hg 12 h after
      the conventional tablet were measured. The numbers of patients achieving the goal
      BP reduction were comparable. There were no significant differences between
      treatments in the nature and severity of adverse events. Long-term efficacy and
      safety of the new formulation were investigated in patients receiving treatment
      for 12 months. After the initial significant reduction, the patients' BP showed a
      trend to a further less pronounced decrease for the remainder of the study. In
      only two patients was the dose readjusted during long-term administration. No
      serious side effects or alterations of laboratory tests occurred. Nifedipine SR
      is effective and safe therapy for elevated BP, with advantages in terms of
      patient acceptability.

PMID- 1378113
TI  - Endothelin dilates bovine pulmonary circulation and reverses hypoxic pulmonary
      vasoconstriction.
AB  - To assess the effects of endothelin 1 (ET) on the pulmonary and systemic vascular
      beds simultaneously, we examined the hemodynamic responses to ET in awake calves
      implanted with a Jarvik total artificial heart (TAH), a device that maintains
      constant cardiac output (CO). During basal conditions, successive incremental
      intravenous (i.v.) injections of 1, 3, and 10 micrograms ET caused a dose
      dependent decrease in pulmonary arterial pressure (PAP), (from 24 +/- 3 to 15 +/-
      1 mm Hg, p less than 0.05) while having no effect on systemic arterial (SAP),
      left atrial (LAP), and right atrial (RAP) pressures. Administration of 30
      micrograms ET i.v. also decreased PAP, had no effect on LAP and RAP, but
      increased SAP from 100 +/- 6 to 118 +/- 4 mm Hg (p less than 0.05). The decrease
      in PAP was rapid, occurring within seconds and lasting 10 min, whereas the
      increase in SAP occurred after 2-5 min and was prolonged for greater than or
      equal to 20 min. As compared with injection in the right atrium, administration
      of 30 micrograms ET into the left atrium reduced PAP to a similar extent, but
      induced a greater increase in SAP (+32.5 +/- 4 vs +17.5 +/- 2 mm Hg, p less than
      0.05). ET also dose-dependently reversed the acute pulmonary vasoconstriction
      induced by inhalation of an hypoxic gas mixture. In all cases, pulmonary
      vasodilation occurred without evidence of short-term tolerance. The results
      demonstrate that ET is a potent in vivo pulmonary vasodilator. In calves, the
      predominant hemodynamic response to ET is pulmonary vasodilation, with systemic
      vasoconstriction apparent only at higher concentrations of the peptide.

PMID- 1378114
TI  - Long-term diuretic therapy: effects of dose reduction on antihypertensive
      efficacy and counterregulatory systems.
AB  - In the present study, the effects of a dose reduction on antihypertensive
      efficacy and metabolic side effects of diuretic therapy were investigated in 36
      hypertensive patients. During the first treatment period of 1 year, the patients
      were treated with 25 mg of the thiazide diuretic bemetizide (n = 18) or 25 mg
      bemetizide plus 50 mg of the potassium-sparing agent triamterene (n = 18). Mean
      blood pressure (BP) values decreased significantly (p less than 0.01) during the
      first year of the trial. Thereafter, doses were reduced to 10 mg bemetizide or 10
      mg bemetizide plus 20 mg triamterene in patients whose BP became normal during
      the first year (n = 16 in both groups). At the end of the second year, equal BP
      control was achieved with doses more than twice smaller than those used during
      the first year. During the second year of the trial, activation of the renin
      angiotensin system (RAS) was significantly less pronounced as compared with the
      first year and the percentage of patients with hypokalemia (less than 3.5 mM)
      decreased from 62.5 to 25% in the bemetizide group. Thus, this long-term study
      provides additional evidence that diuretics have a flat dose-response curve with
      respect to their antihypertensive efficacy, whereas lower doses might cause less
      pronounced activation of counter-regulatory systems. Furthermore, our results
      indicate that long-term studies might be necessary to assess the full
      antihypertensive potential of low doses of antihypertensive agents.

PMID- 1378115
TI  - Effect of oral dilevalol on forearm circulation in essential hypertension.
AB  - In 7 patients with untreated mild essential hypertension, a single 200-mg
      dilevalol dose was administered orally. Blood pressure (BP, left brachial artery
      catheter), heart rate (HR), and left and right forearm blood flows were measured
      and left and right forearm vascular resistances were calculated before and for
      approximately 3 h after drug administration. Dilevalol administration was
      followed by a sustained reduction in BP, little change in HR, and a similar
      pronounced and sustained increase in left and right forearm blood flows and
      reduction in left and right forearm vascular resistances. At the end of the
      observation period, the changes in left forearm circulation were unaffected by
      left brachial artery infusion of saline but markedly reduced by left brachial
      artery infusion of propranolol at doses that had no effect on BP, HR, and
      contralateral forearm vasodilatation. Thus, at an oral dose exerting an
      antihypertensive effect, dilevalol induces a marked and persistent vasodilation
      due largely to the beta-adrenoceptor agonism of the drug.

PMID- 1378116
TI  - Effects of ibopamine on exercise-induced increase in norepinephrine in normal
      men.
AB  - The effects of 100 mg ibopamine, an orally active aselective dopamine (DA)
      agonist, on plasma catecholamines was evaluated in 8 healthy men during
      sympathetic stimulation by graded exercise in a single-blind, placebo-controlled
      cross-over study. The exercise consisted of progressive cycling activity less
      than or equal to 90% of the previously determined VO2max. Graded exercise
      resulted in an increase in systolic and mean blood pressure (SBP, MBP), heart
      rate, norepinephrine (NE) and epinephrine level, with a decrease in diastolic BP
      (DBP). The increase in NE was significantly blunted by ibopamine as compared with
      placebo. No differences for BP, heart rate (HR), or epinephrine between placebo-
      and ibopamine study day were noted. In previous studies, ibopamine decreased
      resting plasma NE in patients with congestive heart failure (CHF), whereas plasma
      NE was not altered by ibopamine in healthy volunteers. This different outcome in
      both categories might therefore be explained by the absence of substantial
      sympathetic stimulation in normal humans at rest. Because it is reasonable to
      assume that the effect of ibopamine on systemic and local hemodynamics is
      negligible as compared with the effect of exercise in the healthy volunteers, the
      plasma decrease caused by ibopamine is probably related to stimulation of DA2
      receptors. In conclusion, ibopamine blunts the increase of plasma NE during
      graded exercise in healthy men.

PMID- 1378117
TI  - Effect of spirapril on left ventricular hypertrophy due to volume overload in
      rats.
AB  - The effect of the angiotensin-converting enzyme (ACE) inhibitor spirapril on
      structural and functional parameters of volume-overloaded rat hearts was
      evaluated in a time-course study. Left ventricular hypertrophy (LVH) was induced
      by graded disruption of the aortic valve in male Wistar rats. Four weeks later,
      structural (LV mass and LV wall thickness) as well as functional parameters [LV
      end-systolic and end-diastolic volumes, stroke volume (SV), ejection fraction
      (EF)] were determined in anesthetized animals by magnetic resonance imaging
      (MRI). The rats were then divided into two groups, one of them receiving
      spirapril (10 mg/kg/day) in food. LV parameters were evaluated by MRI at 4, 18,
      25, and 32 days after treatment was started. MRI analysis before the start of
      treatment showed that both groups had developed a similar degree of eccentric LV
      hypertrophy. Similarly, LV wall thickness, end-systolic and end-diastolic
      volumes, SV, and EF did not differ between the groups. Treatment with spirapril
      resulted in stable LV weight during the follow-up period of 32 days, whereas the
      untreated group showed a significant steady increase in heart weight. LV end
      diastolic volume, LV end-systolic volume, and SV were smaller in the spirapril
      group when measured after 25 and 32 days, but only the difference in end
      diastolic volume reached statistical significance. LV wall thickness and EF were
      not affected by spirapril. After the last MRI determinations, blood pressure (BP)
      and the response to angiotensin I (ANGI) were measured in conscious animals.
      Systolic BP (SBP) and mean arterial pressure (MAP) were significantly lower in
      spirapril-treated rats, and the dose-response curve to ANGI was shifted to the
      right.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378118
TI  - Effects of dopamine receptor and alpha 2-adrenoceptor agonists and antagonists on
      muscarinic receptor stimulation in cardiac sympathetic ganglia of the dog.
AB  - The effects of dopamine (DA)-receptor and alpha 2-adrenoceptor agonists and
      antagonists on ganglionic muscarinic stimulation were examined in anesthetized
      dogs. All drugs were injected or infused intra-arterially into the blood supply
      of the cardiac sympathetic ganglia. The muscarinic agonists McN-A-343 (10, 20,
      and 30 micrograms) and muscarine (1, 2, and 3 micrograms) increased heart rate.
      The muscarinic receptor stimulation elicited by McN-A-343 or muscarine was
      significantly inhibited by infusion of the DA2-receptor agonist quinpirole (3 and
      10 micrograms/min) but not by the DA1-receptor agonist SK&F 38393 (10 and 30
      micrograms/min). The alpha 2-adrenoceptor agonist BHT 933 (3 and 10
      micrograms/min) also inhibited muscarinic receptor stimulation. The DA2-receptor
      antagonist domperidone (10 micrograms/min) and the alpha 2-adrenoceptor
      antagonist yohimbine (1 micrograms/min) had no effects on muscarinic receptor
      stimulation, but they antagonized the inhibitory effects of quinpirole and BHT
      933, respectively. The nicotinic transmission elicited by preganglionic cardiac
      sympathetic nerve stimulation (1 and 2 Hz) was also inhibited by DA-receptor and
      alpha 2-adrenoceptor agonists and antagonists. These results suggest that DA2
      receptors and alpha 2-adrenoceptors suppress muscarinic transmission as well as
      nicotinic transmission in the cardiac sympathetic ganglia of the dog.

PMID- 1378120
TI  - Cilazapril and captopril accelerate recovery from hypoxia in myocardial cell
      aggregates in culture.
AB  - We wished to determine whether angiotensin-converting enzyme (ACE) inhibition
      alters the effect of hypoxia and reoxygenation directly on the cardiac myocyte;
      to compare two different ACE inhibitors, one with and one without a sulfhydryl
      group (i.e., captopril and cilazapril), and to examine the potential interaction
      of these ACE inhibitors with agents that purportedly prevent the deleterious
      action of oxygen-derived free radicals. Ventricular myocytes were obtained from 7
      day-old chick embryo hearts and were maintained in culture for 96 h before study.
      Hypoxia produced a significant (p less than 0.05) and marked reduction in cardiac
      contractile frequency that was not influenced by captopril 10(-6) and 10(-7) M or
      cilazapril 10(-6) or 10(-7) M. During the reoxygenation period, cardiac
      contractile frequency gradually returned to normal. Both ACE inhibitors,
      captopril and cilazapril, were associated with a similar significant (p less than
      0.05) enhancement of restoration of contractile frequency. Angiotensin II (ANGII)
      reversed the effect of these ACE inhibitors. Two agents that reduce reoxygenation
      induced myocardial damage, perhaps through alteration in production or
      degradation of oxygen-derived free radicals, i.e., allopurinol and superoxide
      dismutase (SOD), significantly (p less than 0.05) accelerated recovery of cardiac
      myocytes during reoxygenation. There was no additive effect with either captopril
      or cilazapril plus allopurinol or SOD. Conclusions about the actions of these ACE
      inhibitors must be tempered by the evidence that substrates other than ANGI,
      particularly bradykinin, are processed by the enzyme and inhibited by ACE
      inhibitors so that some of the observed effects may have been due to accumulation
      of other substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378119
TI  - Mechanisms of action of cicletanine in human and guinea pig resistance arteries.
AB  - Human subcutaneous (s.c.) arteries and guinea pig mesenteric vessels (internal
      diameter 150-570 microns) were isolated and mounted on a microvascular myograph.
      Cicletanine-induced relaxation curves were constructed after preconstriction with
      either depolarising potassium (KPSS) or norepinephrine (NE) and in the presence
      and absence of indomethacin, glibenclamide, or tetraethylammonium chloride (TEA).
      Using only guinea pig vessels, cicletanine relaxation curves were constructed
      with and without charybdotoxin. In human vessels, there was no significant
      difference between cicletanine-induced relaxation in vessels preconstricted with
      either NE or KPSS, and neither ATP-sensitive or Ca(2+)-activated K channels were
      involved. However, with indomethacin added, in human vessels the maximal response
      to cicletanine (30 microM) was reduced by 51% (p less than 0.05). In guinea pig
      mesenteric arteries, cicletanine (30 microM) produced a 95% relaxation of the NE
      constricted vessel and only 30% relaxation of the KPSS-constricted vessel (p less
      than 0.001). There was no evidence for any involvement of the ATP-sensitive K
      channel or the eicosanoid system. The relaxation to cicletanine (less than 3
      microM) in with TEA added was greatly reduced (p less than 0.001) and with
      charybdotoxin added the concentration response curve to cicletanine was shifted
      approximately 3 log units to the right (p less than 0.001), suggesting an
      involvement of Ca(2+)-activated K channels. The acute vasodilator action of
      cicletanine is complex, with multiple mechanisms of action, and the relative
      importance of these varies in different species or at least in different vascular
      beds.

PMID- 1378121
TI  - Pretreatment with captopril improves myocardial recovery after cardioplegic
      arrest.
AB  - Among the interventions designed to limit postischemic oxidative injury, those
      that enhance the myocardial content of thiol groups are attractive because thiols
      are powerful antioxidant. Indeed, part of the protection afforded by the
      angiotensin-converting enzyme (ACE) inhibitor captopril in regional myocardial
      ischemia is attributed to its thiol group. This study assesses the effects of
      captopril in a surgically relevant model of global ischemic arrest. Thirty rats
      were implanted subcutaneously (s.c.) with osmotic pumps that allowed continuous
      delivery of captopril (total dose 75 mg), enalapril (a nonthiol-containing ACE
      inhibitor, total dose 7.5 mg) or saline in 48 h. Drug concentrations were
      equipotent in their effect on angiotensin I (ANGI) pressor response. Hearts were
      then excised, perfused under isovolumic conditions, and subjected to 90-min
      cardioplegic arrest at 30 degrees C followed by 1-h reperfusion. Pre- and
      postischemic coronary flows were significantly higher to a similar extent in the
      two drug-pretreated groups than in controls. However, captopril-pretreated hearts
      had the best recovery of contractility (dP/dtmax; 3,590 +/- 74 versus 2915 +/- 64
      mm Hg s-1 in the enalapril group, p less than 0.001), and diastolic pressure
      (13.7 +/- 0.9 mm Hg vs. 20.0 +/- 1.6 mm Hg in the enalapril group, p less than
      0.05). We conclude that pretreatment with ACE inhibitors improves myocardial
      recovery after cardioplegic arrest and that captopril is more effective than
      enalapril. The additional protection afforded by captopril was not flow mediated,
      suggesting that the cardioprotective effects of this drug not only involve an ACE
      inhibition-dependent coronary vasodilation but could be related to a thiol
      dependent limitation of oxidative injury.

PMID- 1378122
TI  - Effects of early angiotensin-converting enzyme inhibition in a pig model of
      myocardial ischemia and reperfusion.
AB  - In a blind, randomized study, the effects of perindopril, a nonsulfhydryl
      containing angiotensin-converting enzyme (ACE) inhibitor, were compared with
      those of placebo in a closed-chest pig model of myocardial infarction. In
      anesthetized pigs, myocardial ischemia and reperfusion were induced by inflation
      and deflation of a catheter balloon in the left anterior descending coronary
      artery (LAD), respectively. Thirty minutes after induction of ischemia and 15 min
      before reperfusion, a bolus injection of 0.06 mg/kg perindoprilat (n = 12), the
      active compound of perindopril, or placebo (n = 12) was administered in the
      pulmonary artery of these animals. After the acute phase of myocardial
      infarction, treatment with 12 mg/day perindopril or placebo was continued orally
      for 2 weeks. During the entire treatment period, 7 of 12 animals died in the
      placebo group versus 2 of 12 animals in the perindopril group (Fisher's exact
      test p less than 0.04). This beneficial effect of perindopril on mortality could
      not be attributed to salvage of myocardial tissue because the increases in
      creatine phosphokinase and coronary venous purine levels were similar in
      perindopril- and placebo-treated animals. Neither were there any significant
      between-treatment differences in the hemodynamic and (neuro)humoral parameters
      during the acute phase of myocardial infarction. The difference in mortality was
      observed within 24 h after myocardial infarction. Prevention of acute pump
      failure and, especially, life-threatening ventricular arrhythmias may explain
      this improvement in survival by perindopril. Retrospectively, logistic regression
      analysis showed that, irrespective of treatment, survival was inversely
      correlated to plasma renin activity (PRA) before induction of ischemia (r = 
      0.33; p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378124
TI  - Efficacy and safety of deferoxamine conjugated to hydroxyethyl starch.
AB  - The efficacy and safety of deferoxamine conjugated to hydroxyethyl starch (HES
      DFO) was evaluated in an in vitro rat cardiac membrane lipid peroxidation (CMLP)
      assay and in a swine model of regional myocardial ischemia/reperfusion injury in
      comparison to DFO. The rat CMLP results demonstrate that HES-DFO is at least as
      potent as DFO (IC50 = 10 and 13 microM, respectively). HES-DFO given
      intravenously (i.v.) at the equivalence of 25 mg/kg and 100 mg/kg DFO in a swine
      model of regional myocardial ischemia [20-min left anterior descending coronary
      artery (LAD) occlusion followed by 60-min reperfusion] showed no significant
      changes in hemodynamics as compared with DFO at 25 mg/kg i.v. In addition, HES
      DFO was at least as potent as DFO with regard to recovery of regional segment
      shortening function (%SS). Furthermore, both HES-DFO and DFO significantly
      reduced tissue water content (edema) in the area at risk (AAR). We conclude that
      conjugation of DFO to HES improves the safety without any interference in the
      efficacy of DFO.

PMID- 1378123
TI  - Effects of SUN-1165, N-(2,6-dimethylphenyl)-8-pyrrolizidine acetamide
      hydrochloride hemihydrate, a new class I antiarrhythmic drug, on ventricular
      arrhythmias, intraventricular conduction, and the refractory period in canine
      myocardial infarction.
AB  - Effects of SUN-1165, a class I antiarrhythmic drug, on ventricular arrhythmias,
      intraventricular conduction, and the effective refractory period (ERP) were
      examined in a canine model of myocardial infarction and compared with those of
      lidocaine. The antiarrhythmic effects were examined on the arrhythmias developed
      24 h after left anterior descending coronary artery (LAD) ligation and
      ventricular premature stimulation-induced arrhythmias 5-7 days after LAD
      ligation. Effects on intraventricular conduction and ERP were also examined in
      animals 5-7 days after LAD ligation. The intraventricular conduction time (CT)
      was determined by excitation induced by a ventricular stimulation at various
      coupling intervals from 200 to 1,000 ms. SUN-1165 (1 and 3 mg/kg) showed a marked
      reduction in the frequency of ventricular ectopic beats 24 h after LAD ligation
      and was more potent than lidocaine. SUN-1165 (1 and 3 mg/kg) prolonged CT in the
      infarcted zones over a wide range of the coupling intervals and produced block of
      severely delayed conduction. In contrast, lidocaine prolonged CT only at short
      coupling intervals. Ventricular premature stimulation produced ventricular
      arrhythmias, which were prevented by pretreatment with SUN-1165 (3 mg/kg). ERP
      was prolonged by SUN-1165 (3 mg/kg). In conclusion, SUN-1165 showed
      antiarrhythmic effects in a canine model of myocardial infarction. A selective
      depression of delayed conduction in the infarcted zone and a prolongation of ERP
      probably contribute to this antiarrhythmic effect.

PMID- 1378125
TI  - Quinaprilat increases total body vascular compliance in rats with myocardial
      infarction.
AB  - To test whether quinaprilat, a new angiotensin-converting enzyme (ACE) inhibitor,
      has any venous effect, we measured its immediate effects on mean circulatory
      filling pressure (MCFP), intravascular volume, and total body vascular (i.e.,
      venous) compliance in conscious rats with healed myocardial infarction induced by
      coronary artery ligation. MCFP was determined by inflating a right atrial balloon
      to arrest the circulation instantly and temporarily. Total body vascular
      compliance was derived from total circulatory pressure-volume relationships as
      determined by series measurements of MCFP with different intravascular volume
      status. In 8 rats with mean infarct size of 26 +/- 4%, 30-min infusion of
      quinaprilat (0.1 mg/kg/min) decreased both mean arterial and central venous
      pressures (MAP, CVP) by 8 and 0.7 mm Hg, respectively (p less than 0.02); heart
      rate (HR), MCFP, hematocrit, and blood volume remained unchanged. As compared
      with control vehicle infusion, quinaprilat increased total body vascular
      compliance (2.09 +/- 0.12 vs. 2.69 +/- 0.23 ml/kg/mm Hg; p less than 0.05) and
      decreased extrapolated unstressed circulating volume (34.96 +/- 1.10 vs. 28.53 +/
      2.55 ml/kg; p less than 0.02). These data suggest that quinaprilat produces
      possible venodilation through improved total body vascular compliance, thereby
      reducing cardiac preload in this rat model of myocardial infarction.

PMID- 1378127
TI  - Combined effect of dietary calcium and calcium antagonists on blood pressure
      reduction in spontaneously hypertensive rats.
AB  - Calcium supplementation and calcium channel blockers are known to have
      antihypertensive effects in similar subsets of hypertensive patients, as well as
      in spontaneously hypertensive rats (SHR). To investigate this apparent paradox,
      we placed 12-week-old SHR on one of three dietary levels of calcium (0.2, 0.4, or
      0.8%), as well as on one of four doses of nifedipine (0, 50, 150, or 300 mg/kg
      food) for 8 weeks. We performed a similar experiment using four verapamil doses
      (0, 300, 900, or 1,800 mg/kg food). In the nifedipine experiment, two-way
      analysis of variance showed significant independent antihypertensive effects of
      both nifedipine (p less than or equal to 0.0001) and calcium (p less than 0.0001)
      and significant interaction (p = 0.0034), the latter suggesting a synergistic
      effect. In the verapamil experiment, both calcium and verapamil again had
      significant independent antihypertensive effects (p = 0.006 and p = 0.004,
      respectively), but there was no significant interaction. Although the effects of
      the calcium supplement or calcium antagonist alone were significant, such
      hypotensive responses were not optimal or predictable or clearly dose-dependent.
      However, the combination of a calcium supplement and calcium antagonist resulted
      in predictable or dose-dependent effects, and the optimal effect was reflected in
      the reduction of the SHR pressure to normal range for Wistar-Kyoto (WKY) rats.
      These results appear to indicate that supplementary calcium and calcium channel
      blockers act by different mechanisms in lowering blood pressure (BP), and that
      the combination of those differing mechanisms of action may have potential
      therapeutic benefit.

PMID- 1378126
TI  - Comparative hemodynamic effects of Org 7797, flecainide, and propafenone in
      anesthetized pigs with developing myocardial infarcts.
AB  - The hemodynamic effects of a new Ic antiarrhythmic agent (Org 7797) were compared
      with those of flecainide and propafenone in anesthetized pigs with developing
      myocardial infarcts. One hour after acute coronary artery occlusion, the only
      significant hemodynamic effect of an intravenous (i.v.) dose of Org 7797 (0.5
      mg/kg) known to prevent ischemia-induced ventricular fibrillation (VF) in dogs
      was a decrease in heart rate (HR) (of 3%) while cardiac output (CO), stroke
      volume (SV), and left ventricular (LV) dP/dtP-1 were unchanged. At four times
      this dose, the only sustained and significant responses to Org 7797 were
      decreased CO and bradycardia, whereas decreases in arterial and LV pressures (BP
      and LVP) and LVdP/dtP-1 were transient. In contrast, a therapeutic dose of
      flecainide (2 mg/kg) induced sustained reductions in CO, SV, LVdP/dtP-1, and LVP
      whereas a similar (therapeutic) dose of propafenone decreased LVP, reduced CO
      partly as a result of bradycardia and decreased LVdP/dtP-1 but not sufficiently
      to decrease SV. Two electrical deaths occurred in each of the propafenone (n = 6)
      and flecainide (n = 7) groups, but arrhythmic deaths did not occur in Org 7797-
      or saline-treated animals. We conclude that Org 7797 in therapeutic doses, unlike
      propafenone and especially flecainide, is not cardiodepressant in animals whose
      cardiac function is already compromised. In addition, there was no evidence of
      proarrhythmogenicity at the doses of Org 7797 used.

PMID- 1378128
TI  - Desensitization of beta-adrenoceptor- and prostaglandin E1 receptor-mediated
      human vascular smooth muscle relaxation.
AB  - Regulation of beta-adrenoceptors in animal tissues and human cell cultures has
      been extensively described; on the other hand, relatively little is known about
      regulation of beta-adrenoceptors in human tissues in vivo. Both beta
      adrenoceptors and the prostaglandin E1 (PGE1) receptors stimulate vasodilation.
      We wondered if prolonged infusion of isoproterenol or PGE1 would cause
      desensitization of smooth muscle relaxation and used the dorsal hand-vein
      compliance technique to investigate this question. After constructing a dose
      response curve to either the beta-agonist isoproterenol or to PGE1 in a
      phenylephrine preconstricted vein, isoproterenol (271 ng/min), PGE1 (956 pg/min),
      or saline was infused for 4 h in separate experiments. There was no change in the
      ED50 or Emax for either isoproterenol or PGE1 after saline infusion. After a 4-h
      infusion of isoproterenol, the maximal vasodilator response to isoproterenol was
      significantly (p less than 0.01) attenuated from 61 +/- 33% to 19 +/- 10%, while
      the ED50 significantly increased (p less than 0.01) from a geometric mean of 37
      to 197 ng/min. After infusion of isoproterenol, the mean maximum PGE1-induced
      venorelaxation of 129 +/- 29% was modestly but significantly (p less than 0.05)
      blunted to 96 +/- 35%, while the ED50 of PGE1 increased significantly (p less
      than 0.01) from a geometric mean of 81 to 398 pg/min. A 4-h infusion of PGE1
      significantly (p less than 0.01) attenuated the maximum response to PGE1 from 73
      +/- 35 to 28 +/- 16%. The maximal vasodilatory response to isoproterenol was also
      significantly blunted (p less than 0.05) from 62 +/- 35 to 42 +/- 41%, with no
      change in ED50.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378129
TI  - Heart rate dynamics after acute cocaine administration.
AB  - We examined heart rate (HR) patterns after a bolus intravenous (i.v.)
      administration of a high (10 mg/kg) dose of cocaine in unrestrained cats. Mean R
      R intervals, SD, and other measures of variability were assessed in three
      periods: waking baseline, early postcocaine administration, and later recovery
      periods. Cocaine resulted in initial tachycardia and reduced HR variability. This
      reduction in variability was independent of changes in the average rate: during
      the recovery period, HR returned to baseline values, but the reduced variability
      persisted. Nonlinear methods of assessment yielded additional results: Cocaine
      introduces a high correlation between one beat and the next and a tendency for
      cardiac accelerations to be followed immediately by decelerations and vice versa.
      The overall effect of the drug is to restrict deviation from a fixed rate.

PMID- 1378132
TI  - Multiple action agents in cardiovascular therapy. Satellite symposium to the 5th
      European Meeting on Hypertension. Milan, Italy, June 11, 1991.

PMID- 1378130
TI  - Selective adenosine-2 agonist produces both direct and reflex tachycardia in
      normotensive rats.
AB  - Hemodynamic responses to intravenous (i.v.) injection of DPMA [N6-[2-(3,5
      dimethoxyphenyl)-2-(2-methylphenyl)ethyl] adenosine); PD 125,944], a potent
      adenosine agonist with a 32-fold selectivity for the adenosine-2 (A2) receptor
      subtype, were characterized in conscious and anesthetized rats. In conscious rats
      instrumented with miniaturized pulsed-Doppler flow probes, i.v. injection of
      increasing doses of DPMA (3-30 micrograms/kg) had little effect on mean arterial
      pressure (MAP, maximal decrease -8 +/- 4 mm Hg) or renal and mesenteric
      resistance (maximal change 8 +/- 14 and 0 +/- 15%, respectively). In contrast,
      DPMA markedly reduced MAP (maximal decrease -61 +/- 8 mm Hg) in a dose-dependent
      (1-30 micrograms/kg) fashion in pentobarbital-anesthetized rats. The A2 agonist
      also caused a sustained, dose-dependent increase in heart rate (HR, maximal
      increase 75 +/- 12 beats/min) in conscious rats. The tachycardia and decrease in
      arterial pressure were completely reversed by i.v. administration of CGS 15943
      (250 micrograms/kg), a selective adenosine receptor antagonist. Pretreatment with
      propranolol or hexamethonium significantly reduced but did not abolish the
      tachycardia, suggesting that the increase in HR was mediated only partially
      through reflex increases in sympathetic tone. These data indicate that (a)
      anesthesia potentiates the depressor actions of DPMA and (b) stimulation of A2
      receptors increases HR through both direct and indirect mechanisms of action.

PMID- 1378131
TI  - Effects of enalapril and clonidine on glomerular structure, function, and atrial
      natriuretic peptide receptors in SHHF/Mcc-cp rats.
AB  - Seven-month-old, lean male SHHF/Mcc-cp rats, a model of spontaneous hypertension,
      progressive renal dysfunction, and congestive heart failure (CHF), were treated
      with either clonidine (CL) or enalapril (EN) or received no treatment (CON) for
      20 weeks. CL significantly decreased systolic blood pressure (SBP), kidney
      weights, and severity of renal lesions as compared with untreated CON. EN
      produced a decrease in SBP comparable to that in CL. Kidney weights and severity
      of renal histologic changes in the EN group were intermediate between those of
      the CL and CON groups. Despite similar plasma atrial natriuretic peptide (ANP)
      concentrations, CL treatment resulted in a significant increase in the density of
      guanylate cyclase-linked glomerular ANP receptors, whereas EN treatment resulted
      in a significant decrease in the total number of ANP receptors and in the number
      of nonguanylate cyclase-linked receptors and an increase in overall binding
      affinity. These findings demonstrate that antihypertensive agents will slow
      progression of renal injury in SHHF/Mcc-cp rats and that CL is more effective
      than EN in alleviating progressive kidney damage in this model. Furthermore,
      different classes of antihypertensive drugs may alter the density or ratio of
      biologically active and clearance ANP receptor sites in the glomerulus.

PMID- 1378133
TI  - Beta-blocking agents with vasodilating action.
AB  - beta-Adrenoceptor-blocking drugs in current use can be separated into two main
      groups: those nonselective and those selective for beta 1-receptors. Members of
      each group reduce cardiac output and lead to an increase in peripheral resistance
      with a concomitant reduction in blood flow. beta-Blocking drugs not only may
      occupy the receptor preventing stimulation but also may have intrinsic
      sympathomimetic activity. Those with marked partial agonist activity at the beta
      2-receptor giving some beta 2-mediated vasodilation can be regarded as the first
      multiple-action beta-blocking drugs. Subsequently, drugs have been developed that
      in addition to blocking the beta-receptor have an important peripheral
      vasodilator activity. Labetalol was the first drug of this group to be developed;
      prizidolol followed but has been withdrawn because of toxicity. Several other
      agents have been described, including bucindolol, carvedilol, celiprolol,
      dilevalol (one of the isomers of labetalol), and medroxolol. Three mechanisms
      have been reported to be responsible for peripheral vasodilation: alpha-receptor
      blockade, beta 2-agonism, and a dilator action independent of either the alpha-
      or beta-receptors. Evidence for these various mechanisms is more readily
      obtainable from animal experiments, but some confirmatory evidence has been
      obtained in humans. Inhibition of alpha-stimulation had been found with
      labetalol, medroxalol, and carvedilol and suggested with celiprolol. beta 2
      Mediated vasodilation has been demonstrated by, for example, celiprolol and
      dilevalol; evidence of a vasodilation independent of alpha-blockade or beta 2
      stimulation has been reported with celiprolol and carvedilol.

PMID- 1378134
TI  - Pharmacokinetics and efficacy of carvedilol in hypertensive patients with chronic
      renal failure and hemodialysis patients.
AB  - The efficacy, safety, and pharmacokinetics of carvedilol were investigated in an
      open trial performed on 13 hypertensive patients with chronic renal failure and
      six additional patients requiring hemodialysis. In hypertensive renal failure
      patients, treatment with carvedilol (5 mg/day) for 1 week produced a significant
      decrease in blood pressure (from 172/101 to 146/84 mm Hg) but did not change the
      heart rate. The pharmacokinetics of carvedilol did not change with repeated
      administration, and there was no accumulation of this drug. In hemodialysis
      patients with hypertension, the pharmacokinetics of carvedilol after a single
      dose of 10 mg did not vary between dialysis and nondialysis days, and blood
      pressure decreased significantly on both days. In addition, there was no
      accumulation of carvedilol during a 4-week trial of therapy, and blood pressure
      was decreased significantly from 170/93 to 145/83 mm Hg. There were no side
      effects and no abnormal laboratory findings noted during the trial. These results
      indicate that carvedilol is an effective and safe agent for hypertensive patients
      with chronic renal failure and for hemodialysis patients with hypertension and
      that dosage adjustments are probably not required in these clinical situations.

PMID- 1378135
TI  - Effects of carvedilol during exercise.
AB  - The effect of carvedilol on cardiovascular and physical performance parameters at
      rest and during exercise was evaluated in an open, uncontrolled study.
      Assessments were made at rest, at one-half anaerobic threshold (1/2AT), at AT,
      and at maximal work load (WLmax) before and after 3 weeks of treatment with 12.5
      mg carvedilol once daily for 1 week, followed by 25 mg carvedilol once daily for
      2 weeks. Ten well-conditioned healthy male volunteers maintained their regular
      training program during the study, and all completed the study. End-of-study
      measures of physical performance (time to WLmax, WLmax, and VO2/kg) and
      behavioral measures (Borg scale) of perceived exertion were unchanged from
      prestudy values. End-of-study diastolic BP (DBP) at rest and at WLmax was
      unchanged compared with prestudy values (mean +/- SD; 81.0 +/- 7.38 and 84.4 +/-
      4.95 mm Hg, respectively, compared with 82.0 +/- 8.88 and 85.0 +/- 7.07 mm Hg,
      respectively). Mean +/- SD change from prestudy to end-of-study baseline resting
      systolic BP (SBP) was a reduction of 11.5 +/- 8.83 mm Hg, and mean +/- SD change
      from prestudy to end-of-study SBP at WLmax was a reduction of 20.0 +/- 12.25 mm
      Hg. Mean +/- SD change from prestudy to end-of-study resting heart rate (HR) a
      reduction of 7.8 +/- 18.45 beats/min, and mean +/- SD change from prestudy to end
      of-study HR at WLmax was a reduction of 19.7 +/- 9.24 beats/min. The effect of
      carvedilol thus represents a combination of reduction in resting systolic BP and
      HR and attenuation of the exercise-induced changes in these parameters.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1378136
TI  - A comparison of carvedilol with a combination of propranolol and isosorbide
      dinitrate in the chronic treatment of stable angina.
AB  - The beta-blocking and vasodilating agent carvedilol was compared with a
      combination of propranolol and isosorbide dinitrate (ISDN) in a double-blind,
      parallel-group study. After two baseline sitting bicycle exercise tests on
      placebo, 31 patients with chronic stable angina were asymmetrically randomized to
      treatment with carvedilol (25 mg b.i.d.) or propranolol-ISDN (80 mg/20 mg b.i.d.)
      for a period of 6 months. Further exercise tests were performed 2 h after the
      first dose as well as after 1, 3, and 6 months of treatment. Twenty-seven
      patients were considered evaluable for efficacy. Differences between the two
      groups were observed with emphasis on total exercise time and time to 1-mm ST
      segment depression. In contrast to a greater peak effect of the first
      propranolol/ISDN dose, the chronic antianginal and anti-ischemic effects of
      carvedilol at trough were found to be more marked than those of the combination.

PMID- 1378137
TI  - Effects of carvedilol on ventricular arrhythmias.
AB  - Carvedilol is a nonselective beta-blocker with alpha-mediated vasodilating
      properties that has been shown to be effective in systemic hypertension, stable
      angina, and congestive heart failure (CHF). In this study, we studied the effects
      of carvedilol on premature ventricular contractions (PVCs) in 65 patients
      undergoing treatment with carvedilol (12.5-50 mg b.i.d.) for 4-8 weeks. Twelve
      patients had hypertension, 41 had stable angina, and 12 had CHF. Holter
      monitoring for 24 h was performed before and after active carvedilol therapy.
      Median PVCs per 24 h decreased from 25.5 to 6.0 (p less than 0.001, n = 52).
      Reduction in PVC activity occurred in 77% of patients, and 23% of patients with
      multifocal PVCs changed their morphology to unifocal. Nonsustained ventricular
      tachycardia was present in four patients before treatment; this was abolished in
      all patients. R-on-T PVC was present in six patients; it decreased in five and
      increased in one. New ventricular tachycardia (less than 8 beats) occurred in two
      patients, but QT prolongation was not noted in these patients. An improvement in
      Lown's classification occurred in 50% of patients. However, in the CHF group, the
      improvement in Lown's criteria was observed in 73% of patients. Carvedilol does
      not appear to possess proarrhythmic effects, and chronic therapy reduces PVC
      activity in a wide range of patients. This property of carvedilol is
      complementary to its hypotensive and anti-ischemic effects. In the CHF group, the
      beneficial effects of carvedilol on left ventricular function and hemodynamics
      may combine with the improvement in PVC activity to produce a significant
      improvement in mortality.

PMID- 1378138
TI  - Constriction of human dorsal hand veins in vivo with several vasoconstrictors and
      the influence of oral administration of carvedilol.
AB  - In vivo measurements of human dorsal hand vein diameters have become a valuable
      tool in investigating vasoactive agents. This study in 13 healthy volunteers was
      performed to establish the influence of locally infused clonidine, angiotensin
      II, norepinephrine, and prostaglandin F2 alpha (PGF2 alpha) on hand vein diameter
      in a nonsystemically active dose range. The study was intended to select agents
      suitable for venous preconstriction before and after oral administration of 50 mg
      carvedilol to obtain information on the mechanisms of vasodilation of this
      combined alpha- and beta-blocker. Infusions of norepinephrine (ED50, 20-40
      ng/min) and PGF2 alpha (ED50, 480-1,170 ng/min) into the hand vein under
      investigation led to nearly complete constriction of the vessel. Infusions with
      clonidine and angiotensin II led to approximately 35% diameter reduction under
      the same conditions. A wide interindividual variety of hand vein dose response
      was observed for all vasoconstrictors. Oral administration of 50 mg carvedilol
      led to a rightward shift in the dose-response curves of angiotensin II,
      norepinephrine, and PGF2 alpha. On a 5% significance level, the venoconstrictive
      effects of norepinephrine and PGF2 alpha were attenuated by carvedilol compared
      with placebo. We conclude that a mechanism of vasodilation by carvedilol in
      addition to alpha-adrenoceptor antagonism could be responsible for the
      attenuation of venoconstriction induced by PGF2 alpha.

PMID- 1378139
TI  - Efficacy and safety of carvedilol in comparison with nifedipine sustained-release
      in chronic stable angina.
AB  - In patients with chronic stable exertional angina pectoris, the antianginal and
      anti-ischemic efficacies and the safety of 25 mg carvedilol b.i.d. were compared
      with those of 20 mg nifedipine sustained-release (SR) in a double-blind,
      randomized, multicenter study. In 22 centers, 166 patients were enrolled. After
      washout and run-in phases with two symptom-limited seated bicycle exercise tests
      on placebo, eligible patients were allocated to one of the two parallel treatment
      groups. After 4 weeks of active treatment, an additional exercise test was
      performed 12 h after the preceding dose. The patients were issued diary cards to
      document the daily number of anginal attacks and glyceryl trinitrate
      applications. Symptom-limited total exercise time, time to onset of angina, and
      time to 1-mm ST-segment depression increased with both treatments vs. placebo
      baseline values. The changes were more distinct in the carvedilol group, but the
      between-group differences were not statistically significant. Angina
      symptomatology during daily life and glyceryl trinitrate consumption were
      markedly improved by each treatment. Adverse events on treatment, particularly
      those correlated to vasodilation, were less frequent in the carvedilol group.

PMID- 1378140
TI  - The once-daily dose regimen of carvedilol: a meta-analysis approach.
AB  - Establishing the overall efficacy or safety of a drug requires a unified
      methodological approach and analysis of all clinical trials that are intended to
      be summarized. As an example, this article presents the aggregated dose-response
      relationship and a subgroup analysis (by age) over all studies of the
      antihypertensive drug carvedilol. The clinical end points were change from
      baseline of blood pressure and pulse after 2-4 weeks of treatment with a once
      daily dose regimen. All antihypertensive trials were reanalyzed using an intent
      to-treat principle. Aggregated data (mean, standard deviation, sample size) for
      each random group within each study were then combined by means of meta-analysis.
      The results show that the main patient population can be treated adequately with
      25 mg of carvedilol q.d. The dose-response curve shows a typical sigmoid shape: a
      steeper increase from 12.5 to 25 mg of carvedilol and a following flat part (25,
      50, and 100 mg of carvedilol q.d.). There is a considerable variation of the
      results between studies, which is much bigger than the dose-response effect. Most
      of this variation is due to monocentric trials.

PMID- 1378141
TI  - Safety of the coadministration of carvedilol and nifedipine sustained-release in
      the treatment of essential hypertension.
AB  - A single-center, randomized, double-blind study in 14 hypertensive patients was
      conducted to investigate the acute and short-term safety of the addition of
      carvedilol to pre-existent nifedipine sustained-release (SR) therapy as well as
      on the addition of nifedipine SR to pre-existent carvedilol therapy when
      treatment with the initial monotherapy did not adequately control blood pressure.
      Mean supine blood pressure at study entry was 171/106 mm Hg. Acute reductions in
      blood pressure were greater with combination treatment than with either
      monotherapy. Dosing with 25 mg carvedilol once daily or 20 mg nifedipine SR twice
      daily resulted in mean peak reductions in supine blood pressure of 21/11 and
      20/16 mm Hg, respectively, after 1 week of treatment with each respective
      monotherapy. With combination treatment, mean peak reductions (after dosing on
      days 1, 3, and 10) ranged from 26 to 40 mm Hg in supine systolic blood pressure
      and from 14 to 23 mm Hg in supine diastolic blood pressure. Acute changes in mean
      standing systolic and diastolic pressures were comparable to those in the supine
      position. Combination treatment resulted in an additive acute antihypertensive
      response without synergistic potentiation. Neither monotherapy nor the
      coadministration of the two agents in the doses used resulted in a significant
      antihypertensive response at the time of trough plasma levels of study
      medication, perhaps due to the short-term nature of the trial which did not allow
      the full antihypertensive effect of either agent to be realized. Before dosing
      with study medication, heart rates were minimally changed from study entry levels
      with either monotherapy or combination treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1378142
TI  - Myocardial protection with carvedilol.
AB  - Carvedilol is a multiple-action cardiovascular agent that is both a beta
      adrenoceptor antagonist and a vasodilator and has recently been made available
      for the treatment of mild-to-moderate hypertension. Clinical trials are ongoing
      to establish the efficacy of carvedilol in angina and congestive heart failure.
      beta-Adrenoceptor antagonists are known to reduce myocardial work secondary to
      reductions in heart rate and contractility; accordingly, they have been shown to
      be cardioprotective in animals and in humans. Because carvedilol has beta
      adrenoceptor antagonist activity, it also should provide significant
      cardioprotection. The additional vasodilating activity of carvedilol, which will
      further reduce myocardial work by decreasing afterload and myocardial wall
      tension, should provide more salvage of ischemic myocardium than that afforded by
      a pure beta-adrenoceptor antagonist, such as propranolol. We investigated the
      ability of carvedilol and propranolol to reduce infarct size in experimental
      models of acute myocardial infarction in the rat, pig, and dog. The left anterior
      descending coronary artery was occluded for 30 (rat) or 45 min (pig) and then
      reperfused for 24 h (rat) or 4 h (pig). In the dog, the left circumflex coronary
      artery was occluded for 60 min and reperfused for 24 h. Vehicle, carvedilol, or
      propranolol was administered intravenously 15 min before ischemia (and, in the
      rat only, repeated 4 h after ischemia). An additional group of dogs was subjected
      to permanent left anterior descending coronary artery occlusion for 6 h, and
      carvedilol or propranolol was given 15 min after occlusion. Infarct size was
      examined on stained tissue sections using quantitative image analysis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1378143
TI  - Disposition of carvedilol enantiomers in patients with liver cirrhosis: evidence
      for disappearance of stereoselective first-pass extraction.
AB  - The racemic drug carvedilol exerts its antihypertensive action through
      vasodilation and nonselective beta-blockade. The R(+)-enantiomer has twice
      (31.1%) the absolute bioavailability than the S(-) form (15.1%). The
      pharmacokinetics of the enantiomers were investigated after intravenous (i.v.)
      (12.5 mg in 1 h) and p.o. (25 mg) administration of racemic carvedilol in six
      patients with cirrhosis of the liver according to a randomized crossover design.
      Although the difference between areas under the curve of R(+) and S(-) were of
      borderline significance after i.v. administration but significant after oral
      administration, no difference existed between the absolute bioavailabilities of
      R(+) (83.7%) and S(-) (71.3%). The enantiomer ratio is similar after i.v. (1.3)
      and p.o. administration (1.6). In contrast to healthy subjects, the apparent
      volume of distribution of S(-) is about 90% greater than that of R(+) in
      patients. The renal excretion of carvedilol and of one of its major metabolites,
      carvedilol glucuronide, also exhibited stereoselective behavior, but in opposite
      directions. In patients with liver cirrhosis, stereoselective metabolism of
      carvedilol is still operative. However, probably because of portocaval shunts,
      the hepatic first-pass extraction is markedly reduced, eliminating the difference
      in bioavailability between the two enantiomers.

PMID- 1378145
TI  - Different vasodilating mechanisms--different peripheral effects?
AB  - Many factors, both local and systemic, are known to influence the caliber of
      peripheral vessels and regional blood flow. Methods of studying limb blood flow
      and its alteration by disease and drugs present considerable problems. We
      compared the effects of a series of antihypertensive drugs on limb blood flow and
      their functional effects in patients with hypertension and peripheral vascular
      disease. Results from studies with new antihypertensive drugs such as carvedilol
      are awaited.

PMID- 1378146
TI  - Carvedilol in hypertension: effects on hemodynamics and 24-hour blood pressure.
AB  - Nineteen men (mean age, 44 years) with moderately severe essential hypertension
      were studied invasively at rest and during exercise. After initial predrug
      recordings, patients received 25 mg carvedilol orally, and central hemodynamics
      at rest and during exercise were recorded 1 and 2 h after tablet intake to
      evaluate the immediate effects of carvedilol. Blood pressure decreased by 11%
      within 1 h, and the hemodynamic results indicated a combination beta-blocking and
      vasodilating effect. After 6-9 months of treatment (dose, 25-100 mg), supine
      hemodynamics were recorded, first 12-24 h after the last dose and then 1 and 2 h
      after an additional 25-mg dose. During chronic treatment (2 h after the last dose
      with the patient at rest and in the supine position), mean arterial pressure was
      reduced by 17% (p less than 0.001) and total peripheral resistance index was
      reduced by 6% (NS), whereas heart rate and cardiac index were reduced by 12%.
      Exercise hemodynamics demonstrated a decrease in blood pressure of 17% (p less
      than 0.001). Exercise stroke index increased by 5% (NS), in part compensating for
      the reduction in heart rate of 17%. Total peripheral resistance index was reduced
      by 5% (NS). Twenty-four-hour blood pressure monitoring (Accutracker II)
      demonstrated significant blood pressure reductions in awake as well as in asleep
      patients. Blood pressures decreased from 163/102 to 141/84 mm Hg in from 135/78
      to 122/68 mm Hg in awake and asleep patients; respectively. Carvedilol is an
      effective antihypertensive agent, and the hemodynamic mode of action reflects
      alpha 1- and beta 1-blocking activities.

PMID- 1378144
TI  - Alpha 1-blocking properties of carvedilol during acute and chronic
      administration.
AB  - Carvedilol is a beta-adrenergic-blocking drug with vasodilating properties. This
      vasodilation has been ascribed to alpha 1-adrenergic blockade, but it has never
      been shown in the clinical setting. We addressed this issue by studying eight
      patients with mild essential hypertension who were given prazosin, 2 mg or
      carvedilol, 25 mg p.o. following a 2-week washout from previous treatment,
      according to a randomized double-blind, crossover experimental design. Before and
      2 h after the administration of either prazosin or carvedilol, the patients were
      infused i.v. with increasing doses of phenylephrine (0.2-1.2 microgram/kg/min)
      and isoproterenol (0.01-0.05 microgram/kg/min). The patients were thereafter
      maintained on carvedilol 25 mg daily for 3 weeks, and the i.v. phenylephrine and
      isoproterenol infusions were repeated 2 h after the last tablet administration.
      The results showed that the single dose of carvedilol and prazosin lowered blood
      pressure (beat-to-beat finger pressure measurement) to a similar extent, but that
      heart rate was unaffected by prazosin and reduced by carvedilol. The tachycardic
      response to isoproterenol was abolished by carvedilol and unaffected by prazosin,
      whereas the pressor response to phenylephrine was reduced by carvedilol and
      virtually abolished by prazosin. The antihypertensive, beta-blocking and alpha 1
      adrenergic-blocking effects of carvedilol were unchanged following prolonged
      administration of the drug. Thus, at a clinically effective dose, carvedilol not
      only has beta- but also sizeable alpha 1-blocking effects. These effects are
      preserved during prolonged administration of the drug. For a comparable
      antihypertensive action, however, the alpha 1-blocking effect is less pronounced
      than that of an alpha 1-blocker such as prazosin.

PMID- 1378147
TI  - Hemodynamic effects of carvedilol after acute oral administration in hypertensive
      and normal subjects.
AB  - Forearm hemodynamics using pulsed Doppler flowmetry were studied in nine healthy
      volunteers and 12 patients with mild-to-moderate hypertension before and after
      acute oral administration of the beta-blocking and vasodilating agent carvedilol.
      Both the 25- and the 50-mg dose produced a significant blood pressure reduction
      by comparison with placebo in normotensive and hypertensive subjects. Only the 50
      mg dose caused a decrease in forearm vascular resistance in hypertensive
      subjects. The decrease disappeared after wrist occlusion. Although brachial
      artery diameter did not change, a significant decrease in tangential tension was
      observed. This study provides evidence that carvedilol produced arteriolar
      dilation within the forearm of hypertensive subjects in association with a
      decrease in brachial artery tangential tension.

PMID- 1378148
TI  - Blood pressure lowering and cerebral blood flow: a comparison of the effects of
      carvedilol and propranolol on the cerebral circulation in hypertensive patients.
AB  - The first part of this article concerns the general relation between blood
      pressure lowering and cerebral blood flow. Factors known to affect cerebral blood
      flow are reviewed, and recent advances in the field of innervation of cerebral
      blood vessels are outlined. Special emphasis is placed on the importance of the
      phenomenon of autoregulation and how this is disturbed in patients with
      hypertension. Not all antihypertensive drugs exert the same action on the
      cerebral circulation to produce the same blood pressure-lowering effect. In
      addition, the actions exerted by common antihypertensive drugs on the cerebral
      circulation are described. The second part of the article provides a comparison
      between the effect of carvedilol and that of propranolol on blood pressure
      reduction and cerebral blood flow. In a double-blind, crossover study involving
      14 patients with mild-to-moderate hypertension, carvedilol was shown to have no
      effect on cerebral blood flow, whereas there was a slight tendency for lower
      flows to occur with the use of propranolol. Because of the small sample size,
      statistical significance was not reached. These results are consistent with other
      recently published findings.

PMID- 1378149
TI  - Use of multiple-action agents on the heart: pathophysiological and therapeutic
      considerations.
AB  - The introduction of beta-adrenoreceptor antagonists into clinical practice has
      resulted in major progress in the treatment of hypertension, angina pectoris, and
      congestive heart failure. However, the first and second (beta 1 selective)
      generations of beta-blockers induce a series of unwanted functional and metabolic
      effects, suggesting the search for a third generation of beta-antagonists. The
      new multiple-action beta-blockers, which have important peripheral vasodilator
      properties, appear to be promising with regard to clinical efficacy and side
      effects. In hypertensive patients, the vasodilation could add a more
      pathophysiological mechanism and therefore could induce a better preservation of
      systolic function. The global cardioprotection may be further improved by the
      absence of long-term metabolic effects. By virtue of their peripheral and
      coronary vasodilating properties, multiple-action beta-blockers could exert more
      favorable anti-ischemic effects in patients with angina pectoris than the
      traditional beta-blockers. In congestive heart failure, afterload reduction, and
      possibly myocardial beta 2-activation induced by multiple-action beta-blockers
      can minimize the negative inotropic effects, leading to better toleration at the
      beginning of treatment. The potential benefits of multiple-action beta-blockers
      have been assessed by preliminary studies and should be confirmed by trials in
      progress.

PMID- 1378150
TI  - Vasodilatory action of carvedilol.
AB  - Carvedilol is a dual-acting drug designed to produce two complementary effects:
      beta-blockade and vasodilation. These effects are induced in the same dose range,
      a prerequisite for utilizing both properties in an appropriate manner. The
      vasodilation is mediated predominantly by specific alpha 1-adrenoceptor blockade.
      At markedly higher concentrations, additional vasodilating actions besides alpha
      1-blockade can be observed. These effects resemble those of Ca(2+)-antagonistic
      properties. However, they do not contribute to the acute blood pressure-lowering
      activity of carvedilol but may be responsible for the increased blood flow to
      specific organs. At beta-blocking doses, carvedilol reduces the regional and
      systemic vascular resistance in various experimental models, healthy volunteers,
      and in patients with cardiovascular diseases such as hypertension, coronary
      artery disease, and heart failure. The profile of carvedilol thus insures
      beneficial treatment of hemodynamic disorders characterized by increased
      sympathetic tone and increased vascular resistance.

PMID- 1378151
TI  - Effect of carvedilol on left ventricular function and mass in hypertension.
AB  - The effects of carvedilol, a nonselective beta-blocker with peripheral
      vasodilator action, on left ventricular function and mass in essential
      hypertension were studied in 14 patients with diastolic filling abnormalities.
      Treatment produced significant decreases in blood pressure (systolic: 168.4 +/-
      10.5 to 154 +/- 17.2 mm Hg, p less than 0.005; diastolic: 101.6 +/- 8.6 to 95.3
      +/- 11.6 mm Hg, p less than 0.025), left ventricular mass (316.7 +/- 85.8 to
      276.8 +/- 84.9 g, p less than 0.05), and left ventricular mass index (157.9 +/-
      42.4 to 131.6 +/- 34.6 g.m-2, p less than 0.025). There were coincident
      improvements in the parameters of diastolic left ventricular filling (E/A ratio:
      0.66 +/- 0.14 to 0.80 +/- 0.26, p less than 0.025; mean E descent velocity: 245
      +/- 130 to 264 +/- 70 cm.s-2, p less than 0.05). No significant alterations in
      systolic function were observed, although three patients with systolic impairment
      improved to normal during treatment. Two other patients, however, were withdrawn
      from the study because of hypotension and cardiac failure. In conclusion,
      carvedilol is effective in the treatment of hypertension and produces adequate
      blood pressure control with a percentage reduction in left ventricular mass. The
      associated changes in diastolic function may be due in part to the mass
      reduction, but no direct relation has been established, and the effect of
      afterload reduction on diastolic left ventricular filling remains important.

PMID- 1378152
TI  - Regression of left ventricular hypertrophy.
AB  - Since our first studies on hypertrophy regression, this parameter has achieved an
      increasing interest in the treatment of hypertension. During the past 8 years we
      studied different groups of antihypertensive drugs with the use of magnetic
      resonance imaging (MRI). This article discusses the antihypertensive drug
      carvedilol. We examined 17 patients with diastolic blood pressure of at least 95
      mm Hg and left ventricular wall thickness of at least 15 mm. Measurements were
      carried out before and after treatment with 25 mg/day carvedilol for 6 months. We
      demonstrated a significant regression of septal thickness from 17.7 to 16.3 mm.
      At each wall, three measurements at different points were performed by MRI and
      the means were calculated. Left ventricular ejection fraction and wall motion did
      not show any significant changes in radionuclide ventriculography after
      treatment. The diastolic blood pressure was reduced from 98.0 to 88.7 mm Hg. All
      differences are significant (p less than 0.05). There was no significant
      correlation between the extent of regression of septal hypertrophy and the degree
      of pretherapeutic hypertrophy, the age of patients, or the dimension of blood
      pressure reduction.

PMID- 1378153
TI  - Can intravenous beta-blockade predict long-term hemodynamic benefit in chronic
      congestive heart failure secondary to ischemic heart disease? A comparison of
      intravenous with oral carvedilol.
AB  - Several studies have demonstrated the long-term beneficial effects of beta
      blockers in the treatment of congestive heart failure. Despite interest in this
      mode of therapy, clinical application of beta-blockers has been limited due to
      their negative inotropic effect. A subset of the heart failure patients do not
      show improvements with standard beta-blocker therapy. Carvedilol, a new
      nonselective beta-blocking agent with concurrent alpha-blocking properties, was
      evaluated in 17 patients with chronic heart failure secondary to ischemic heart
      disease. All had resting left ventricular ejection fraction less than or equal to
      45% and were maintained on diuretic therapy. Acute hemodynamic measurements were
      made after administration of intravenous carvedilol (2.5-7.5 mg) and after
      chronic therapy for 8 weeks (12.5 to 50 mg b.i.d.). Radionuclide
      ventriculography, ambulatory intra-arterial blood pressure monitoring, and right
      heart catheterization were performed before and after 8 weeks of chronic therapy.
      Twelve patients completed the study (five were withdrawn). Symptomatic and
      hemodynamic improvements were demonstrated in 11 of the 12 patients after 8 weeks
      of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378154
TI  - Receptor pharmacology of carvedilol in the human heart.
AB  - The beta-blocker and vasodilator carvedilol was examined in preparations of human
      ventricular myocardium. Carvedilol is a high-affinity, slightly beta 1-selective
      competitive beta-blocking agent, with a KD for beta 1-receptors of approximately
      4-5 nM and a selectivity of sixfold to 39-fold for beta 1-receptors rather than
      beta 2-receptors, depending on the method used to assess subtype potency.
      Carvedilol also is a potent alpha 1-blocking agent, with a beta 1: alpha 1
      blocking relative potency of 1.7-fold. In human lymphocytes containing beta 2
      receptors and human myocardial membranes containing both beta 1- and beta 2
      receptors, carvedilol exhibited the unique property of guanine nucleotide
      modulatable binding. This is a property shared with bucindolol, another beta
      blocker and vasodilator that is structurally similar to carvedilol. Despite the
      presence of guanine nucleotide-modulatable binding, no intrinsic activity of
      carvedilol was detected in preparations of isolated human heart or in myocardial
      membranes.

PMID- 1378155
TI  - A comparison of carvedilol with atenolol in the treatment of mild-to-moderate
      essential hypertension. INT-CAR-07 (U.K.) Study Group.
AB  - The efficacy and safety of carvedilol, a beta-blocker with vasodilating
      properties, were compared at a dosage of 25 to 50 mg once daily with those of
      atenolol at a dosage of 50-100 mg once daily in a double-blind, randomized,
      parallel-group, multicenter study. After a single-blind placebo phase of 3 to 6
      weeks, 47 patients (median age, 59 years) were randomized to receive carvedilol
      and 52 patients (median age, 57 years) were randomized to receive atenolol for an
      8-week study period. Patients on carvedilol received 12.5 mg for the first 2 days
      and then 25 mg as a once-daily dosage. The initial dosage of atenolol was 50 mg
      once daily. The dosage of each treatment could be doubled (to 50 and 100 mg once
      daily, respectively) at week 4 if the response was inadequate. Sitting and
      standing blood pressures and heart rates were recorded 24 h after the dose at
      weeks 4 and 8. Data from 90 of 98 patients who completed the study were eligible
      for per-protocol analysis. Approximately one-third of the patients in each group
      required upward dose titration at week 4 because of inadequate response. At week
      8, 84% patients receiving carvedilol and 91% receiving atenolol had sitting
      diastolic blood pressure less than or equal to 90 mm Hg or decreased their blood
      pressure by greater than or equal to 10 mm Hg (95% confidence intervals for
      difference between carvedilol and atenolol, +7% and -21%). Safety profiles were
      similar between treatments. One patient withdrew; a skin rash developed during
      the fourth week of treatment with atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378156
TI  - Comparison of the effects of carvedilol and nifedipine in patients with essential
      hypertension and non-insulin-dependent diabetes mellitus.
AB  - The safety and tolerability of carvedilol, a new antihypertensive agent with the
      combined pharmacological activities of beta-blockade and vasodilation, and of
      nifedipine were investigated in patients with essential hypertension and non
      insulin-dependent (type II) diabetes mellitus. Twenty patients were openly
      randomized to receive 25 mg carvedilol once daily (five men and five women; mean
      age, 63 years) or 10 mg nifedipine t.i.d. (three men and seven women; mean age,
      64 years) for a period of 4 weeks. Baseline mean sitting blood pressures were
      168/98 and 169/95 mm Hg in the carvedilol and nifedipine groups, respectively.
      Baseline mean areas under the curve (AUC) of the intravenous glucose tolerance
      test (IVGTT) for the carvedilol and nifedipine groups were 6,136 +/- 1,195 and
      6,287 +/- 1,228 mg/dl/min, respectively. Demographic and efficacy variables were
      not statistically different between treatment groups. After 4 weeks of therapy,
      mean sitting blood pressure was significantly (p less than 0.02) reduced to
      144/91 mm Hg in the carvedilol group and to 149/87 mm Hg in the nifedipine group.
      Week 4 IVGTT AUC values of 5,735 +/- 1,464 mg/dl/min in the carvedilol group and
      5,988 +/- 993 mg/dl/min in the nifedipine group, representing mean reductions of
      6.14% and 3.17%, respectively, were not statistically different from baseline.
      Both treatments were well tolerated. No patient experienced adverse events in the
      carvedilol treatment group, whereas two patients in the nifedipine group reported
      episodes of headache (one patient) and palpitations (one patient); each episode
      was mild in severity and considered to be related to study medication.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1378157
TI  - Effects of carvedilol on atrial natriuretic peptide, catecholamines, and
      hemodynamics in hypertension at rest and during exercise.
AB  - Possible counterregulatory neurohumoral and hemodynamic responses to carvedilol
      (a new vasodilating nonselective beta-receptor blocker) were studied in 19 men
      with essential hypertension (age range, 34-59 years; mean age, 44 years). Intra
      arterial pressure, cardiac output (Cardio-green), heart rate, and the vasoactive
      peptides norepinephrine, epinephrine, and atrial natriuretic peptide (ANP) were
      measured at rest supine and sitting and during 100-W bicycle exercise before and
      2 h after administration of 25 mg carvedilol. The same protocol was followed
      after 9 months of chronic carvedilol treatment (mean dose, 52 mg/day). Carvedilol
      induced both acute and chronic reductions (at rest supine, 11%) in mean arterial
      pressure, due in part to reduction in cardiac output (5%) and in part to
      reduction in total peripheral resistance (5%). At rest supine, carvedilol induced
      a reduction in ANP (27%) that could be viewed as a counterregulatory response to
      decrease in cardiac output, preventing excessive blood pressure reduction. ANP
      decreased (18%) when the patient sat up from the supine position and increased
      (67%) during exercise, but no further change was seen after acute or chronic
      carvedilol treatment. With the patient in the sitting position, norepinephrine
      was 110% higher than at rest supine; during 100-W exercise, norepinephrine
      increased 368%. A further increase (38-86% in the three situations, respectively)
      was seen after the first dose of carvedilol. Epinephrine showed similar but less
      marked changes. Neither extracellular fluid volume nor plasma volume (isotope
      dilution techniques) changed significantly during the study, but the acute blood
      pressure response to carvedilol was directly related to changes in extracellular
      fluid volume.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378158
TI  - Effect of long-term carvedilol therapy on renal function in essential
      hypertension.
AB  - We assessed the long-term effects of carvedilol on renal function in 10 patients
      with mild-to-moderate essential hypertension. After a 2- to 4-week placebo run-in
      period, all patients received 5 mg carvedilol once daily. If the effect was
      insufficient, the dosage was successively increased to 10 or 20 mg once daily.
      The mean +/- SEM duration of treatment was 17.3 +/- 1.0 weeks, and the final mean
      daily dosage was 13.5 +/- 2.2 mg/day. With treatment, systolic and diastolic
      blood pressures decreased significantly from 159.7 +/- 1.3 to 140.5 +/- 3.2 mm Hg
      (p less than 0.001) and from 98.3 +/- 1.0 to 88.2 +/- 2.7 mm Hg (p less than
      0.001), respectively. Carvedilol did not cause significant changes in glomerular
      filtration rate, effective renal plasma flow, blood urea nitrogen, or serum
      creatinine. Renal vascular resistance decreased significantly from 12.7 +/- 1.4
      to 11.2 +/- 1.2 dyne.s.cm-5/1.48 m2 x 10(3) (p less than 0.05). Thus, long-term
      carvedilol therapy was effective in reducing blood pressure in essential
      hypertension without causing impairment of renal function.

PMID- 1378160
TI  - Immunocytochemical investigation of normal and chronic lymphocytic leukaemia
      lymphocytes reveals unexpectedly frequent reactivity with some myelomonocytic
      associated antibodies.
AB  - Information about the expression of some myelomonocytic markers in lymphocytes of
      patients with B-CLL is scarce. We studied the CD13, CD14, CD11c and CD68 surface
      antigens in 42 controls and in 38 patients with B-CLL to detect their possible
      reactivity. Eighty-nine percent of B-CLL expressed very strongly the CD14
      antigen; on the contrary, the other myelomonocytic antigens tested were very
      weakly expressed. Forty-one of 42 controls showed a few CD14-positive lymphocytes
      with a statistical difference between normal and CLL lymphocytes. No statistical
      difference was recorded either between CD14 expression and Rai's staging system
      or Binet's stages, nor between CD14 and bone marrow involvement and doubling time
      or between CD14 and heavy or light chain expression. A minor B lymphocytic subset
      in humans coexpresses the CD14 and CD5 antigens, it being increasingly speculated
      that B chronic lymphocyte leukaemias originate precisely from this B CD5- and
      CD14-positive cells. Just as the CD5 antigen is regarded as an excellent B-CLL
      marker, it seems to us that a strong expression of the CD14 antigen might have
      the same diagnostic relevance.

PMID- 1378159
TI  - Functional significance of induction of differentiation in human myeloid
      leukaemic blasts by 1,25-dihydroxyvitamin D3 and GM-CSF.
AB  - We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and granulocyte
      macrophage colony stimulating factor (GM-CSF) on monocytic differentiation of the
      U937 leukaemic cell line and blasts from patients with AML. 1,25(OH)2D3 and GM
      CSF synergistically increased functional and phenotypic aspects of
      differentiation in the U937 cell line. In addition, the effective concentration
      of 1,25(OH)2D3 was reduced by up to 100 times in the presence of GM-CSF. GM-CSF
      alone had little differentiation-inducing effect on AML blasts. 1,25(OH)2D3
      induced CD14 antigen expression in 67% AML blast populations and increased
      functional activation in 36%. 1,25(OH)2D3 and GM-CSF in combination cooperated to
      further induce CD14 antigen expression in one third of blast populations, while
      having no further effect on function. Failure to induce functionally effective
      levels of FcRII antigen on AML blasts following stimulation with 1,25(OH)2D3 and
      GM-CSF may account for the lack of functional activation.

PMID- 1378161
TI  - Modulation of leukemic cell growth by tumor necrosis factor: action and
      expression in myeloid leukemia.
AB  - Normal and leukemic bone marrow cells were studied in the presence of tumor
      necrosis factor alpha (TNF) together with granulocyte colony-stimulating factor
      (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in
      clonogenic assays. Cells of four normal volunteers, three patients with chronic
      myeloid leukemia, 16 patients with acute non-lymphocytic leukemia (ANLL), and six
      patients with myelodysplastic disorders were compared. Our results show four
      patterns of response to TNF in the presence of G-CSF or GM-CSF: (a) increased
      sensitivity to inhibition by TNF relative to the response of normal bone marrow
      cells; (b) response indistinguishable from normal bone marrow cells; (c)
      refractoriness to TNF at all doses; (d) synergistic growth stimulation with both
      G-CSF and GM-CSF. Leukemic cells of eight additional ANLL patients were incubated
      in a 3H-thymidine incorporation assay, and three patterns of reactivity to TNF
      were observed: (a) decreased 3H-thymidine uptake in the presence of TNF; (b) no
      response to TNF at all doses; and (c) increased 3H-thymidine uptake in response
      to TNF. Leukemic cells of 26 ANLL patients of various FAB-types were examined for
      the production of TNF mRNA by Northern blot analysis. TNF mRNA could be detected
      in cells of eight patients, predominantly in the M5B FAB type. Our data show that
      the growth response of leukemic cells to TNF is not uniform and was not
      determined by FAB category.

PMID- 1378162
TI  - Human recombinant stem cell factor stimulates in vitro proliferation of acute
      myeloid leukemia cells and expands the clonogenic cell pool.
AB  - Stem cell factor (SCF) is a new growth factor acting on early hematopoietic
      progenitor and stem cells. In our experiments human recombinant SCF stimulated
      short-term proliferation of accessory cell-depleted acute myeloid leukemia (AML)
      cells in 13/14 cases, as determined by 3H-thymidine (3H-TdR) incorporation and
      cell counts. Stimulatory activity was significantly greater than in the presence
      of GM-CSF and was comparable to that of granulocyte colony-stimulating factor (G
      CSF), interleukin 3 (IL-3), and 5637 cell line supernatant (SN). Conversely, the
      ability of SCF to induce primary colony formation by AML clonogenic cells (CFU-L)
      was lower than that of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      and 5637 SN in all but four cases. However, SCF potentiated the stimulatory
      effect of GM-CSF, G-CSF, and IL-3 on both 3H-TdR incorporation and colony
      formation. In a 7-day liquid culture SCF enhanced CFU-L recovery in all cases to
      a significantly greater extent than the other growth factors. A further increment
      was obtained by combinations of SCF with GM-CSF, G-CSF, or IL-3, and this was
      significantly more effective than 5637 SN. SCF did not induce leukemic cell
      differentiation. Human recombinant SCF is therefore highly efficient in
      stimulating AML cell proliferation and expanding the CFU-L pool. It was not,
      however, able to support long-term growth of AML cells (beyond 2-7 weeks) in five
      cases tested.

PMID- 1378163
TI  - c-kit gene expression in CD7-positive acute lymphoblastic leukemia: close
      correlation with expression of myeloid-associated antigen CD13.
AB  - Expression of human c-kit proto-oncogene and interleukin-7 receptor (IL-7R) in
      acute lymphoblastic leukemia (ALL) cells expressing CD7 was examined by Northern
      blot analysis and reversed transcription polymerase chain reaction (RT-PCR) assay
      in relation to the phenotypes. Leukemic cells from four out of 12 CD7+ ALL
      patients, all of which fulfilled the criteria of ALL in the FAB classification,
      expressed c-kit genes. Surface CD3 (sCD3) was absent in all of these cases, while
      cytoplasmic CD3 (cCD3) was found in the two sCD3- cases. CD3 epsilon transcripts
      were detected in one of the sCD3- cCD3- cases. IL-7R genes were transcribed in
      the three cases with c-kit gene expression. In addition, there was a good
      correlation between c-kit gene expression and myeloid associated antigen CD13
      positivity of the leukemic cells. None of the patients with c-kit gene expression
      had mediastinal tumor. Our results show that leukemic cells in a proportion of
      CD7+ ALL express receptors for cytokines that are secreted by bone marrow stromal
      cells. Ligands for c-kit genes and IL-7 could play an important role for the
      regulation of proliferation and differentiation of T-cell progenitors in bone
      marrow.

PMID- 1378164
TI  - Development of a colonic release capsule dosage form and the absorption of
      insulin.
AB  - Since the colon is relatively low in peptidase activity and drainage into the
      lymphatics is maximized, a peroral dosage form was developed to deliver insulin
      to the colon. Microemulsions, used as a vehicle for insulin, were gelled using
      Cab-O-Sil, and filled into gelatin capsules pretreated with formaldehyde vapor.
      The capsules were coated with Eudragit NE 30 D, Eudragit S100 and cellulose
      acetate phthalate polymers of pH-dependent and time-controlled release
      mechanisms. In vitro dissolution profiles of the capsule coating, using sodium
      salicylate as the marker, show that dissolution of the capsule begins at 4 h, at
      pH 5.5, and is completed at 8 h, at pH 7.7, simulating the gastrointestinal
      transit and pH profile of the dog. An in vivo crossover study in beagle dogs was
      carried out employing the following treatments: i.v. insulin, p.o. insulin
      microemulsion and colonic release capsule dosage form without insulin (CRC), were
      used as controls, a colonic release capsule dosage form with insulin (CRI) and
      additionally with sodium laurylsulfate (CRIL) or aprotinin (CRIA) as sorption
      promoter and enzyme inhibitor, respectively. Evaluation was done by measuring the
      reduction in blood glucose concentration levels. The pharmacological availability
      (P.A.) is the ratio of the area under the baseline curve (AUC), expressed as
      percent glucose reduction from baseline vs time, of the p.o. dosage forms to i.v.
      insulin administration, corrected for body weight and dose size. The P.A. for the
      p.o. microemulsion, CRC, CRI, CRIL and CRIA were 2.1, 0.4, 5.0, 2.7 and 6.2%,
      respectively. Insulin release occurred throughout the GI tract, with the
      exception of the stomach. Tmax occurred at 6.4 h for CRIA; the majority of
      insulin is taken up after the colonic arrival time is reached in the dog (4-6 h).
      Duration of the reduction in blood glucose levels occurred for 14 h with the CRIA
      dosage form.

PMID- 1378166
TI  - Does aprotinin affect blood loss in liver transplantation?

PMID- 1378165
TI  - Relation of neovascularisation to metastasis of non-small-cell lung cancer.
AB  - The growth of a tumour beyond a certain size requires angiogenesis. We assessed
      whether intensity of angiogenesis correlates with metastasis of non-small-cell
      lung cancer by counting microvessels and grading their density within the initial
      carcinomas in 87 T1N0M0 patients. After radical surgery, metastases developed in
      22. Both microvessel count and density grades correlated significantly with
      metastatic disease as well as tumour size and proliferative activity. The
      likelihood of metastasis increased as the vessel count increased. On multivariate
      analysis, the microvessel density count was the only independent predictor of
      metastasis.

PMID- 1378167
TI  - IgE-mediated anaphylactic reaction to aprotinin during anaesthesia.

PMID- 1378168
TI  - PSA-con-A binding ratio in benign prostate hyperplasia and prostate cancer.

PMID- 1378169
TI  - Serum protease inhibitors promote anchorage-independent growth of transformed
      cells in serum-free medium.
AB  - The effect of three serum serine protease inhibitors on the serum-free agar
      growth of an SV40-transformed 3T3 cell line was investigated. Antithrombin III,
      alpha-2-macroglobulin and alpha-1-antitrypsin were found to potently stimulate
      colony growth in a semisolid medium because of their anti-proteolytic properties.
      These results indicate that protease inhibitors can facilitate tumor cell growth
      in serum-free agar cultures and suggest that the stimulatory effect of serum on
      the growth of certain transformed cells in agar may at least partially be due to
      the high levels of protease inhibitors found in serum.

PMID- 1378170
TI  - Yes, AFP is found in fetal serum.

PMID- 1378171
TI  - Purification of AMPA type glutamate receptor by a spider toxin.
AB  - A glutamate receptor was purified from Triton X-100-solubilized bovine cerebellum
      membranes. The purification was carried out in two steps: affinity chromatography
      using a spider toxin (Joro spider toxin; JSTX) immobilized on a lysine-agarose
      column, and a Mono Q anion exchange column. Sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) of the purified active fraction showed a single
      band with Coomassie Blue staining, which migrated with a M(r) = 130,000. The
      specific [3H]amino-3-hydroxy-5-methyl-isoxazole propionate ([3H]AMPA) binding
      activity of the affinity-purified fraction was 2095-fold higher than that of the
      crude soluble fraction. Lineweaver-Burk plot analysis showed a Kd of 12.7 nM
      [3H]AMPA in the purified fraction. The purified fraction was examined with patch
      clamp recording methods in reconstituted liposomes. A glutamate-activated channel
      was observed and was inhibited with JSTX. The rank order of potency of agonists
      inducing channel currents was AMPA = glutamate greater than quisqualate much
      greater than kainate greater than NMDA. Thus, there is strong evidence that the
      130 kDa protein is a purified component of the native AMPA type glutamate channel
      of bovine cerebellum.

PMID- 1378172
TI  - Subcutaneous fluid infusion (hypodermoclysis) in palliative care: new role for an
      old trick.

PMID- 1378173
TI  - Insulin releasing effects of mastoparan and amphiphilic substance P receptor
      antagonists on RINm5F insulinoma cells.
AB  - It has been proposed that mastoparan (INLKALAALAKKIL) and other mast cell
      secretagogues such as substance P (SP) or compound 48/80 act by direct activation
      of the pertussis toxin (PTX)-sensitive G-proteins in intact cells. Here we have
      investigated whether or not the antagonists of SP, [D-Trp7,9,10] SP1-11 and [D
      Trp7,9,10, N-leu11]SP1-11, can similarly induce exocytosis from RINm5F cells. In
      intact cells mastoparan and the SP antagonists stimulated insulin release in a
      dose-dependent manner at concentrations ranging from 10 to 100 microM. The
      maximal effect on insulin release, of both mastoparan and the SP antagonists was
      comparable to that obtained with 100 microM forskolin. Pretreatment of the intact
      cells, for 18 h with PTX or 6 h with cholera toxin, did not change the responses
      induced by both mastoparan and the SP antagonists. This absence of PTX effect,
      despite the fact that the three PTX substrates at 41, 40 and 39 kDa were ADP
      ribosylated after pretreatment suggests intrinsic differences between mast and
      RINm5F cells. Thus the SP antagonists behave similarly to mastoparan in its
      ability to induce insulin release in RINm5F cells. However, the higher
      concentrations required with RINm5F cells compared to that needed for mast cells
      suggest differences either in G-proteins composition or in the phospholipid
      composition of the membranes.

PMID- 1378175
TI  - Quantitative structure-mutagenic activity relationships of triazino indole
      derivatives.
AB  - The mutagenicity of 3-(4'-benzylidenamino)-5H-1,2,3-triazin[5,4-b]-indol-4-one
      derivatives, new compounds with considerable platelet antiaggregating activity,
      was assayed with the Ames test using the Salmonella typhimurium strains TA97,
      TA98, TA100 and TA102. The adaptive least-squares method (ALS method) was used to
      carry out a quantitative structure-activity relationship (QSAR) analysis. Three
      equations, based on 10 congeners, were found for strains TA97, TA98 and TA100.
      The results suggest that lipophilicity of the substituent decreases the
      mutagenicity of the series.

PMID- 1378176
TI  - DNA strand breakage by hydroxyphenyl radicals generated from mutagenic
      diazoquinone compounds.
AB  - The mutagenic diazoquinone compounds p-diazoquinone (p-DQ), o-diazoquinone (o-DQ)
      and 3-diazo-N-nitrosobamethan (D-BM) cleaved the phosphodiester bond of lambda
      DNA, phi X174 RFI DNA and M13mp8ss DNA. p-DQ also cleaved the phosphodiester bond
      of bis(p-nitrophenyl)phosphate. The breakage of the phosphodiester bond was
      inhibited by the antioxidant butyl hydroxyanisole (BHA), ethanol, the spin
      trapping agent DMPO, cysteine and 2-mercaptoethanol. While incubation of p-DQ and
      o-DQ alone gave p-hydroquinone and catechol, respectively, incubation of these
      compounds in the presence of BHA and ethanol gave phenol in large yields.
      Incubation of p-DQ and o-DQ with the spin trapping agents DMPO and PBN gave spin
      adducts assignable as p- and o-hydroxyphenyl adducts, respectively. The breakage
      of the phosphodiester bond of DNA by the diazoquinone compounds is suggested to
      be due to the hydroxyphenyl radicals generated during incubation.

PMID- 1378177
TI  - Cytochrome P450 induction and mutagenicity of 2-aminoanthracene (2AA) in rat
      liver and gut.
AB  - The aim of our study was to establish a relationship between the ability of rat
      liver and gut to activate 2-aminoanthracene (2AA) into mutagens and their P450
      enzyme composition. Rats were orally pretreated with beta-naphthoflavone (beta
      NF), phenobarbital (PB), dexamethasone (DEX) or acetone (AT). Mutagenic
      activation of 2AA was detected in the Ames test. P450IA1, IA2, IIB1/B2 and IIE1
      were immunochemically quantified by Western blots. All the results were compared
      to those obtained in untreated rats. In all tissues, beta NF treatment
      considerably increased the mutagenicity of 2AA. PB treatment significantly
      reduced the mutagenicity of 2AA in the liver but not in the intestine. By
      contrast, AT treatment significantly decreased the number of revertants in the
      duodenum but not in the liver whereas DEX treatment significantly decreased the
      number of revertants in both tissues. 2AA appears to be metabolized by various
      P450s in both organs. In the liver, reactive metabolites may be produced after
      metabolism by the P450IA subfamily. The other P450 enzyme seems to play a part in
      the metabolism of 2AA leading to formation of either mutagenic or non-mutagenic
      metabolites.

PMID- 1378174
TI  - Insulin and orthovanadate stimulate multiple phosphotyrosine-containing serine
      kinases.
AB  - Using the synthetic peptide substrate Kemptide and cytosolic extracts of mouse
      fibroblasts transfected with a human insulin receptor cDNA construct, we have
      studied an insulin-sensitive serine kinase activity. This activity is rapidly
      stimulated by insulin (maximum within 5 min) and also by orthovanadate. During
      cell extract preparation, para-nitrophenylphosphate and phosphotyrosine are able
      to preserve the enzyme activity, while phosphothreonine and phosphoserine fail to
      do so. Using antiphosphotyrosine antibodies, specific immunoprecipitation of this
      insulin- and orthovanadate-sensitive serine kinase was obtained. We then analysed
      by gel filtration chromatography eluates containing tyrosine-phosphorylated
      proteins obtained from unstimulated, insulin- and vanadate-treated cells. We
      found that several activities, with molecular weights estimated to be 30 kDa and
      smaller, are stimulated by both, insulin and orthovanadate. As a whole, our data
      indicate that insulin and orthovanadate enhance the cytosolic content in at least
      2 or 3 phosphotyrosine-containing serine kinase activities.

PMID- 1378178
TI  - Cytogenetic mechanisms in the selective toxicity of cyclophosphamide analogs and
      metabolites towards avian embryonic B lymphocytes in vivo.
AB  - Cyclophosphamide (CP) is selectively toxic to avian and mammalian B lymphocytes,
      but the mechanisms of action are incompletely understood. We used a structure
      activity approach to determine the cytogenetic mechanisms underlying the
      selective lymphoid toxicity in chicken embryos at 18-19 days of incubation. Two
      doses of 5-bromo-2'-deoxyuridine (BrdU; 3 mg/200 microliters x 2) were pipetted
      onto the inner shell membrane to label lymphocyte DNA over 20 h. A single dose of
      the CP analogs or metabolites was given 1 h after the initial BrdU application.
      After a terminal 3-h exposure to demecolcine to block cells in metaphase, the
      embryos were sacrificed at hour 20, and their bursae and thymi were removed for
      cytogenetic processing. Microscope slide preparations of metaphases were stained
      by the fluorescence-plus-Giemsa technique to differentiate the sister chromatids
      for an assessment of sister-chromatid exchange (SCE) induction and cell cycle
      progression based on replication cycle-specific staining patterns. Isophosphamide
      (1.25-40 mg/kg), phosphoramide mustard (0.7-45.7 mg/kg), and 4
      methylcyclophosphamide (1.3-42.1 mg/kg) selectively damaged B cells as shown by
      dose-related reductions in the mitotic activity, inhibition of cell cycle
      kinetics, and approximately 9-15-fold increases in the SCE frequency above
      control. B cells were up to 392 times more susceptible to the toxicity of these
      three bifunctional alkylating agents compared to T cells based on reductions in
      the mitotic activity. At most of the drug doses tested, the T-cell mitotic index
      was not depressed significantly and was usually higher than the control value by
      as much as 50-60%. Importantly, monochloroethylcyclophosphamide (70-245 mg/kg;
      monofunctional alkylation) did not induce differential lymphoid toxicity,
      although a 9-fold increase in the SCE frequency of B cells was observed at the
      highest dose. Didechlorocyclophosphamide (181-422 mg/kg; acrolein generation
      only) was a weak SCE inducer (approximately 1.8-fold increase) and was not
      selectively toxic to B cells. Our data show that selective toxicity to B
      lymphocytes is strongly associated with bifunctional alkylation via the
      chloroethyl groups rather than with monofunctional alkylation and acrolein
      mediated damage. In addition, the results with phosphoramide mustard and 4
      methylcyclophosphamide emphasize that aldehyde dehydrogenase activity is not the
      primary determinant in the relative sparing of T lymphocytes in vivo.

PMID- 1378179
TI  - Sensitivity of different bacterial assays in detecting mutagens in urine of
      humans exposed to polycyclic aromatic hydrocarbons.
AB  - The urine mutagenicity and excretion of 1-hydroxypyrene (1-OH PYR) in non-smoking
      psoriatic patients treated topically with coal-tar-based ointments were analysed
      in order to find the most appropriate procedure for monitoring occupational PAH
      exposure. The bacterial mutagenicity assays used were the plate incorporation,
      macro-scale fluctuation and microsuspension tests, all on Salmonella typhimurium
      strain TA98 in the presence of S9 mix and beta-glucuronidase. The sensitivities
      of the three assays in detecting mutagenic urinary PAH metabolites were compared.
      The efficiencies of XAD-2 and C18 resins for concentrating PAH urinary mutagens
      were evaluated in the microsuspension assay. The plate and fluctuation tests on
      XAD-2 urine extracts were shown to be insufficiently sensitive to detect low
      urinary levels of mutagens, being positive on urine samples with very high PAH
      metabolite content, estimated as more than 30 micrograms/g of creatinine of 1-OH
      PYR. The microsuspension assay on XAD-2 or, even better, on C18 urine extracts
      was very sensitive in detecting up to 5 micrograms/g of creatinine of 1-OH PYR.
      It therefore seems to be applicable to the biological monitoring of most
      occupational low exposures to coal tar.

PMID- 1378180
TI  - DNA damage induced by cigarette smoke condensate in vitro as assayed by 32P
      postlabeling. Comparison with cigarette smoke-associated DNA adduct profiles in
      vivo.
AB  - Cigarette smoke induces a multitude of bulky/aromatic DNA adducts in vivo as
      revealed by 32P-postlabeling assay. The formation of such adducts is thought to
      involve metabolic activation of aromatic chemicals especially polycyclic aromatic
      hydrocarbons (PAHs) present in tumor-initiating cigarette tar fractions, via
      cytochrome P450-associated monooxygenases. Because radicals are present in both
      the gas and particulate (tar) phase of cigarette smoke and in aqueous extracts of
      cigarette smoke condensate (CSC), we addressed the question as to whether
      cytochrome P450-independent, possibly free radical-mediated reactions may
      contribute, also, to formation of cigarette smoke-associated bulky DNA adducts.
      Rat-lung DNA was incubated with aqueous extracts of CSC in the absence of
      microsomes under various conditions and analyzed by 32P-postlabeling.
      Radioactively labeled bulky reaction products were found to accumulate in a time-
      and CSC concentration-dependent manner. The resulting chromatographic profiles
      resembled cigarette smoke-associated DNA-adduct patterns observed in vivo.
      Pretreatment of aqueous CSC extract with radical scavengers/reducing agents
      (ascorbic acid, glutathione) diminished adduct formation in a concentration
      dependent manner. Adduct formation in vitro may involve oxygen-free radicals,
      which are known to be present in aqueous CSC extracts and could (i) attack DNA
      directly to produce bulky adducts, (ii) induce radical sites on DNA covalently
      binding CSC components, or (iii) convert CSC components to DNA-reactive
      electrophiles. In addition, DNA may react with direct-acting mutagens in CSC.
      Adduct fractions derived from in vitro and in vivo experiments showed similar
      chromatographic behavior, suggesting that metabolic activation as well as
      processes not involving metabolism lead to formation of smoking-induced bulky DNA
      adducts in vivo.

PMID- 1378181
TI  - A Drosophila simulans mutant strain sensitive to benzo[a]pyrene and 2
      acetylaminofluorene.
AB  - We have identified a Drosophila simulans mutant, 364 yu, that is sensitive to the
      toxic effects of the procarcinogens B(a)P and 2-AAF. Heterozygotes obtained by
      crossing it to the wild resistant Turku strain (female 364 yu x male Turku) were
      more sensitive than heterozygotes obtained from the reciprocal cross (female
      Turku x male 364 yu) to both the toxic and the mutagenic effects of B(a)P in
      Drosophila tests that measured lethality and the induction of somatic mosaicism,
      respectively. The non-carcinogens pyrene, B(e)P and 4-AAF were only weakly toxic
      and non-mutagenic. In the Ames test B(a)P activation with S15 fractions prepared
      from the homogenates of Drosophila larvae and imagoes of the 364 yu strain, as
      well as of the more resistant D. melanogaster y ++/+ w sn3 heterozygotes, did not
      significantly increase the number of S. typhimurium TA100 revertants even
      following pretreatment with inducers of microsomal monooxygenases (B(a)P, PCB,
      PB). As for 2-AAF, a certain increase was observed following only PB, but not
      B(a)P pretreatment. Possible mechanisms of B(a)P and 2-AAF sensitivity of the 364
      yu strain, and perspectives on using it for monitoring genotoxic environmental
      pollutants, are discussed.

PMID- 1378182
TI  - Mutagenic activation of benzo[a]pyrene by human red blood cells.
AB  - The induction of sister-chromatid exchanges (SCEs) and micronuclei (MN) was used
      as an endpoint to evaluate the cytogenetic effects of benzo[a]pyrene (B(a)P)
      activated by human red blood cells and S9 mix. Human erythrocytes can
      metabolically activate B(a)P. It was shown that both human erythrocytes and S9
      mix activate B(a)P and that the resulting excess SCE and MN depend in a linear
      manner on the B(a)P dose. HPLC analysis suggested that quinone derivatives formed
      by the red blood cells are responsible for the cytogenetic abnormalities
      observed.

PMID- 1378183
TI  - Induction of chromosomal damage by restriction endonuclease in CHO cells porated
      with streptolysin O.
AB  - A procedure is described for the poration of living CHO cells with the bacterial
      cytotoxin streptolysin O (SLO) which allows the introduction into cells of the
      restriction endonuclease Pvu II to mimic and model the effects of ionising
      radiation in causing chromosomal damage. The dependence of this clastogenic
      effect of Pvu II on SLO concentration was measured by assaying the formation of
      micronuclei in cytokinesis-blocked binucleate cells. The optimum concentration
      was found to be 0.045 U/ml. Using the micronucleus assay, the time-course of
      expression of chromosome damage was investigated and found to show a biphasic
      kinetic with time. Using a sampling time of 30 h, a dose-effect curve for
      micronucleus induction by Pvu II was generated. Using this optimized SLO
      treatment protocol, the frequency of metaphase chromosome damage was subsequently
      investigated and found to be also linearly related to Pvu II concentration and
      total aberrations were approximately double the frequency of micronuclei. The
      induction and repair kinetics of DNA double-strand breaks were investigated in
      CHO cells treated with SLO and Pvu II using the neutral filter elution technique
      at pH 9.6. The data presented show that SLO can be used as an alternative method
      for porating cells to allow the introduction of restriction endonucleases into
      cells.

PMID- 1378184
TI  - Photo-enhancement of the mutagenicity of 9-anilinoacridine derivatives related to
      the antitumour agent amsacrine.
AB  - The frameshift mutagenicity of the DNA intercalating drug proflavine is known to
      be enhanced by photoirradiation of bacterial cultures. To determine whether this
      phenomenon was also present in acridine-derived antitumour drugs, cultures of
      Salmonella typhimurium were exposed to the antileukaemia agent amsacrine and the
      experimental agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide
      dihydrochloride (acridine carboxamide) in the presence or absence of visible
      light. A small increase in mutagenicity was observed with amsacrine but not with
      acridine carboxamide. A series of analogues of amsacrine were then tested, and a
      striking relationship was found between the minimum drug concentration for
      mutagenicity and DNA binding affinity. In each case, photoirradiation was
      associated with a small increase in mutagenicity. Each of the compounds showing
      the photo-enhancement effect was capable of reversible one-electron oxidation. It
      is suggested that this oxidation occurs in bacteria, and that the DNA binding
      constant of the resulting acridine radical species will increase because of the
      extra positive charge. This increased DNA binding would be sufficient to explain
      the photo-enhancement of mutagenicity of these drugs.

PMID- 1378185
TI  - Cloning properties of T lymphocyte subpopulations after treatment with 8
      methoxypsoralen and UVA irradiation.
AB  - The cloning rate of PHA-stimulated T lymphocytes after treatment with 8
      methoxypsoralen plus UVA irradiation described by Wunder and Reischmann (1983)
      gives a linear dose-effect relationship at low dosages. However, with increasing
      doses a flattening of the negative gradient occurs. This relationship deviates
      from the classical exponential curve which can be observed when fibroblasts are
      treated with mutagens and which is explainable by a 'recovery plateau' at lower
      dosages. In this study we show that some subpopulations of T lymphocytes, in
      particular the T-helper and T-suppressor cells, influence the overall dose-effect
      relationship. These isolated subpopulations exhibit varying sensitivities in
      comparison with their depleted cell populations. It may be assumed that
      heterogeneous cell populations exist within each isolated subpopulation which may
      be separated into further subclasses according to their specific sensitivity.

PMID- 1378186
TI  - The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD
      1 mice.
AB  - Benzene is a widely used chemical and common environmental contaminant. It is
      carcinogenic in man and animals and is genotoxic in mice, rats, and
      occupationally exposed humans at doses above one part per million. In order to
      evaluate the genotoxic effects of prolonged exposures to very low concentrations
      of benzene, we exposed CD-1 mice to benzene by inhalation for 22 h per day, seven
      days per week for six weeks at 40, 100 and 1000 parts per billion (ppb).
      Additional groups were exposed to purified air or were housed in standard plastic
      cages. The effects of in vivo exposure to benzene were evaluated by using an
      autoradiographic assay to determine the frequency of mutants which represent
      mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in
      spleen lymphocytes. At the end of the six weeks exposure period lymphocytes were
      recovered from the spleens of the mice and cryopreserved prior to assay. Mutant
      cells were selected on the basis of their ability to incorporate tritiated
      thymidine in the presence of 6-thioguanine. The weighted mean variant (mutant)
      frequencies (Vf) of female mice (three per group) were 7.2 x 10(-6) at 0 ppb;
      29.2 x 10(-6) at 40 ppb; 62.5 x 10(-6) at 100 ppb and 25.0 x 10(-6) at 1000 ppb.
      The Vf of unexposed mice housed in standard cages was 13.2 x 10(-6). In male mice
      the same pattern of response was observed, but the increases in Vf in response to
      benzene were not as great. In both sexes of mice, the increases at 40 and 100 ppb
      were significantly greater than at 0 ppb (P less than 0.05). The increase in Vf
      with exposure to 100 ppb and the decline at 1000 ppb parallel the results
      observed for chromosome damage in spleen lymphocytes from the same animals (Au et
      al., Mutation Res., 260 (1991) 219-224). These results indicate that sub-chronic
      exposure to benzene at levels below the current Occupational Safety and Health
      Administration Permitted Exposure Limit may induce gene mutations in lymphocytes
      in mice.

PMID- 1378187
TI  - Analysis of phage M13mp2 mutants produced from transfection of phage DNA having
      N4-aminocytosines at defined sequence positions.
AB  - N4-Aminocytidine is mutagenic in various organisms. In the cell, this cytidine
      analog is metabolized into N4-aminodeoxycytidine 5'-triphosphate, which will then
      be incorporated into DNA and mutation will result during the replication of the
      DNA. To prove that the N4-aminocytosine residue in DNA is indeed the site of
      mutagenesis, we prepared a series of phage M13mp2 DNA samples that bear N4
      aminocytosine residues at a few defined positions in the lacZ alpha region, by
      carrying out in vitro limited extension of primed phage DNA. We then transfected
      the DNAs to Escherichia coli and examined the progeny phages for the forward
      mutations. The M13mp2 DNAs bearing N4-aminocytosines produced mutant phages at
      high frequencies. Furthermore, DNA sequencing of the resulting mutants
      demonstrated that both AT-to-GC and GC-to-AT mutations took place at those
      positions where N4-aminocytosine residues were originally present.

PMID- 1378189
TI  - Diminished genotoxicity of mitomycin C and farmorubicin included in
      polybutylcyanoacrylate nanoparticles.
AB  - The genotoxic effects of mitomycin C (MMC) and farmorubicin (FR) in a free form
      and included in polybutylcyanoacrylate nanoparticles (PBCN) were studied
      employing the Salmonella/microsome mutagenicity assay and the micronucleus test
      in mouse bone marrow as well as in mouse fetal liver. The data obtained clearly
      indicated that MMC (0.25-2.00 micrograms/plate) was a strong mutagen in S.
      typhimurium TA102, while the same concentrations of this compound in PBCN were
      ineffective in inducing his+ revertant mutations in bacterial cells. A similar
      total suppression of mutagenic activity of FR (1.0-20.0 micrograms/plate) was
      registered in S. typhimurium TA98 when the drug was included in PBCN.
      Furthermore, the incorporation of MMC (2.0 or 4.0 mg/kg, i.p.) into PBCN strongly
      diminished or even abolished its clastogenic activity in the bone marrow of
      virgin and pregnant mice as well as in mouse fetal liver, respectively. In
      addition, a lack of genotoxic effect of PBCN only was also established. The toxic
      activity of MMC in mouse bone marrow was significantly reduced or completely
      abolished after its inclusion in PBCN. A conclusion might be drawn that the
      genotoxic activity of some antitumor drugs might be markedly diminished or even
      abolished after their incorporation in PBCN.

PMID- 1378188
TI  - Substitution of p- and o-hydroxyphenyl radicals at the 8 position of purine
      nucleosides by reaction with mutagenic p- and o-diazoquinones.
AB  - Incubation of 2'-deoxyadenosine (dAdo), 2'-deoxyguanosine (dGuo), adenosine,
      guanosine (Guo), thymidine, deoxycytidine with p- and o-diazoquinones, mutagens
      produced by the reaction of phenol and nitrite, at pH 7 and 37 degrees C resulted
      in a decrease of each nucleoside depending upon the concentration of the
      diazoquinones. pD-dAdo, pD-dGuo and pD-Guo were isolated from the reaction
      mixtures of dAdo, dGuo and Guo, respectively, with p-diazoquinone at pH 9.5, and
      oD-dGuo was from the mixture of dGuo and o-diazoquinone at pH 9.5. The products
      were identified as 8-(p-hydroxyphenyl)- and 8-(o-hydroxyphenyl)-purine
      nucleosides by 1H- and 13C-nuclear magnetic resonance spectra, secondary ion mass
      spectrum, ultraviolet absorption spectrum and elemental analysis. p- and o
      Diazoquinones may be converted into p- and o-hydroxyphenyl radicals,
      respectively, which in turn attack the 8 position of the purine nucleosides. The
      mutagenicity of these diazoquinones may be partly due to the radical reactions.

PMID- 1378190
TI  - Photoreactivation implicates cyclobutane dimers as the major promutagenic UVB
      lesions in yeast.
AB  - Previously we compared the mutational specificities of polychromatic UVB (285-320
      nm) and UVC (254 nm) light in the SUP4-o gene of the yeast Saccharomyces
      cerevisiae. Striking similarities in the types and distributions of induced SUP4
      o mutations were consistent with roles for cyclobutane dimers and pyrimidine(6
      4)pyrimidone photoproducts in mutation induction by UVB. To assess the relative
      importance of cyclobutane dimers, we have now examined the effect of
      photoreactivation (PR), which specifically reverses these lesions, on UVB and UVC
      induction of SUP4-o mutations. PR reduced the frequencies of both UVB and UVC
      mutagenesis by approximately 75%. Collections of 138 and 158 SUP4-o mutants
      induced by treatment with UVB plus PR or UVC plus PR, respectively, were
      characterized by DNA sequencing and the results were compared to those for 208
      UVB and 211 UVC-induced mutants analyzed earlier. PR decreased the frequency of
      UVB-induced G.C----A.T transitions by 85%, diminished the substitution
      frequencies at individual sites by 64% on average, and reduced the mutation
      frequencies at the five UVB hotspots by 87%. A more detailed examination revealed
      that the transition frequencies at the 3' base of 5'-TC-3' and 5'-CC-3' sequences
      were decreased by 90% and 72%, respectively. Finally, PR appeared to occur to the
      same extent on both the transcribed and non-transcribed strands of SUP4-o.
      Similar results were obtained for PR following UVC irradiation. Our findings
      indicate that cyclobutane dimers are responsible for the majority of UVB
      mutagenesis in yeast.

PMID- 1378191
TI  - Nondisjunction induced by ethanol in Drosophila melanogaster females.
AB  - The effect of ethanol on chromosomal segregation was investigated in Drosophila
      melanogaster females homozygous for a structurally normal X chromosome marked
      with the recessive mutation yellow (y/y). For chronic treatments the females were
      kept from eclosion in food supplemented with 10% or 15% (v/v) ethanol, mated 24
      or 48 h later to wild-type males and brooded in freshly prepared ethanol food.
      For the acute treatments 24- or 48-h-old females were exposed for 60 min to a 75%
      (v/v) ethanol solution by means of soaked tissue paper placed at the bottom of
      regular culture vials and brooded daily after mating. The results obtained show
      that: (1) both treatments significantly increased the frequency of X-chromosome
      nondisjunction; (2) after acute treatment this effect declined in later broods;
      (3) the yield of malformed flies in the progeny of acutely treated females was
      significantly higher than control values and also declined in later broods; (4)
      ovary analysis showed that chronic ethanol treatments caused a cessation of egg
      production. The induction pattern of nondisjunction and malformed flies is
      interpreted as giving support to the assumption that these effects may result
      from a direct action of ethanol. Ethanol toxicity was assessed by exposing
      females of different ages to a 50% or a 75% (v/v) solution for 60 min and
      counting the surviving flies 24 h later. The surviving fraction decreased steeply
      from 1-day-old (100%) to 5-day-old females (1.8%). It is suggested that toxicity
      may have been due to the action of a metabolite of ethanol, probably
      acetaldehyde.

PMID- 1378192
TI  - Unscheduled DNA synthesis in human hair follicles after in vitro exposure to 11
      chemicals: comparison with unscheduled DNA synthesis in rat hepatocytes.
AB  - A new method is described to investigate unscheduled DNA synthesis (UDS) in human
      tissue after exposure in vitro: the human hair follicle. A histological technique
      was applied to assess cytotoxicity and UDS in the same hair follicle cells. UDS
      induction was examined for 11 chemicals and the results were compared with
      literature findings for UDS in rat hepatocytes. Most chemicals inducing UDS in
      rat hepatocytes raised DNA repair at comparable concentrations in the hair
      follicle. However, 1 of 9 chemicals that gave a positive response in the rat
      hepatocyte UDS test, 2-acetylaminofluorene, failed to induce DNA repair in the
      hair follicle. Metabolizing potential of hair follicle cells was shown in
      experiments with indirectly acting compounds, i.e., benzo[a]pyrene, 7,12
      dimethylbenz[a]anthracene and dimethylnitrosamine. The results support the
      conclusion that the test in its present state is valuable as a screening assay
      for the detection of unscheduled DNA synthesis. Moreover, the use of human
      tissues may result in a better extrapolation to man.

PMID- 1378193
TI  - Chromosomal aberration analysis in peripheral lymphocytes of radiation workers.
AB  - Chromosomal aberration analyses were performed in two groups of radiation workers
      and in a group of healthy controls. Although the level of exposure was below the
      accepted annual limit of 50 mSv, the yields of chromosome fragments and of total
      aberrations were significantly higher in the radiation workers than in the
      controls. However, the frequencies of dicentric and ring chromosomes in the
      radiation workers were not significantly different from those in the controls.

PMID- 1378194
TI  - Mutagenicity of 2-methylpropene (isobutene) and its epoxide in a modified
      Salmonella assay for volatile compounds.
AB  - The mutagenic properties of 2-methylpropene (MP) and 2-methyl-1,2- epoxypropane
      (MEP) were investigated in the Salmonella assay. A simple exposure system,
      consisting of gastight tissue culture flasks, was used. This method has the
      advantage that the volatile test chemical is present during the entire incubation
      period and that several concentrations of the investigated compound can be tested
      on a single day. MP is not mutagenic in strains TA100, TA102 and TA1535, and in
      the latter strain not even in the presence of metabolizing S9 mix. MEP is
      mutagenic in all the strains tested, as demonstrated by a clear dose-response
      relationship. Strain TA1535 seems to be most sensitive to MEP compared with the
      other bacterial strains studied. For this strain, the mutagenic activity of MEP
      decreased significantly in the presence of S9 mix, compatible with the epoxide
      being inactivated by epoxide hydrolase and by glutathione S-transferase, as
      reported previously. From the present study it can be concluded that the parent
      compound MP is not mutagenic, but that its primary metabolite MEP is a mutagenic
      substance. However, very high concentrations are necessary to induce a mutagenic
      effect and the epoxide is efficiently detoxified by different liver enzymes.

PMID- 1378195
TI  - Skin cytogenetic assay for the detection of clastogens-carcinogens topically
      administered to mice.
AB  - A method for assessing the effect of clastogens on mouse skin epidermal cells was
      devised and applied. Toxic and mutagenic responses in epidermal cells were tested
      using two known mutagens and carcinogens, urethane (URE) and 7,12
      dimethylbenz[a]anthracene (DMBA). Cell generation time, sister-chromatid
      exchanges (SCE) and chromosomal aberrations (CA) after topical and
      intraperitoneal (i.p.) treatment were measured in epidermal and bone marrow
      cells. After topical administration both tissues responded similarly, whereas
      after i.p. treatment skin cells were less responsive than bone marrow cells.
      However, the results indicate the validity of this new cytogenetic approach for
      the assessment of the genotoxicity of compounds applied directly to skin.

PMID- 1378196
TI  - Use of a T-lymphocyte clonal assay for determining HPRT mutant frequencies in
      individual rats.
AB  - Conditions for detection and isolation of HPRT- mutants in cloned rat T
      lymphocytes from individual adult Lewis rats were determined. Similar to cloning
      of human T-cells, best results were obtained with lectin (PHA)-primed T
      lymphocytes of rats. High cloning efficiencies, occasionally exceeding 50%, could
      be obtained when the target cells employed were isolated from cervical lymph
      nodes. Feeder cells used were splenocytes, irradiated with 40 Gy of X-rays after
      priming with Con A. Human interleukin-2, present in LAK supernatant, proved to be
      capable of inducing proliferative activity of rat T-lymphocytes and could replace
      conditioned medium from primed rat splenocytes. Under the conditions described in
      this paper, the frequency of mutants in the HPRT gene of T-lymphocytes in Lewis
      rats was about 80% lower than that found in human T-lymphocytes from adults. The
      inverse relationship between mutant frequency and cloning efficiency, clearly
      demonstrated for human data, could not be established for rats. Treatment of rats
      with N-ethyl-N-nitrosourea, a potent alkylating agent, resulted in a time- and
      dose-dependent induction of HPRT- mutants, demonstrating the usefulness of this
      system to study in vivo mutagenesis.

PMID- 1378197
TI  - Assessment of radiation-induced DNA damage in human blood lymphocytes using the
      single-cell gel electrophoresis technique.
AB  - The ability of the alkaline single-cell gel (SCG) electrophoresis technique to
      detect single-strand breaks and alkali-labile DNA damage in human cells induced
      by low doses of radiation was evaluated. Peripheral blood lymphocytes were
      irradiated with gamma-rays from a 137Cs source at doses from 0.01 to 1 Gy and
      exposed to alkali (pH greater than 13) for 20, 40 or 60 min and then
      electrophoresed at 25 V and 300 mA for either 20 or 40 min. The extent of DNA
      damage that was expressed and detected as DNA migration depended directly on the
      dose of radiation, the duration of exposure to alkali and the length of
      electrophoresis. At all experimental conditions tested, it was possible to detect
      a significant increase in DNA damage induced by a radiation dose as low as 0.05
      Gy. Based on an analysis of the ratio of the range to the standard deviation for
      each radiation dose and experimental condition, the distribution of damage among
      cells for all doses was neither excessively homogeneous nor heterogeneous.
      Furthermore, the distribution was independent of radiation treatment. The SCG
      technique is rapid and sensitive, and useful for investigations concerned with
      effects of low doses of radiation.

PMID- 1378198
TI  - Quantitative integration of the Salmonella microsuspension assay with
      supercritical fluid extraction of model airborne vapor-phase mutagens.
AB  - Vapor-phase mutagens are potentially a major class of toxic contaminants in
      ambient and indoor air. These compounds are not routinely analyzed due to a lack
      of an established integrated methodology to quantitatively trap, extract and test
      the compounds in a bioassay. In a previous report, we emphasized the trapping of
      volatile and semi-volatile mutagens and the extraction of these compounds using
      supercritical carbon dioxide (CO2). In the present study, we discuss the use of a
      bioassay for the quantitation of the model mutagens, ethylene dibromide(EDB) and
      4-nitrobiphenyl (4-NB), trapped from an airstream. The compounds EDB and 4-NB
      were released into a controlled airstream, trapped on XAD-4 adsorbent, and were
      extracted using supercritical CO2. The extract was tested in a microsuspension
      modification of the Ames Salmonella/microsome test adapted for volatile
      compounds. Linear dose-response relationships were obtained for supercritical CO2
      extracted EDB using tester strain TA100 (+/- S9) and for 4-NB using tester
      strains TA98 and TA100 (-S9). Standard dose-response curves with known amounts of
      the compounds were also determined for comparison with measured amounts of the
      model compounds collected in an airstream. The gas chromatographic (GC)- and
      bioassay-determined quantities of EDB and 4-NB were highly correlated, accurate
      and precise. For example, bioassay-determined EDB concentrations were within 10%
      of the GC-determined concentrations. Our results demonstrate that the integrated
      methodology for vapor-phase mutagens developed in this study would be useful for
      quantitative analysis of these and related airborne vapor-phase mutagenic
      compounds.

PMID- 1378199
TI  - Evaluation of in vitro cytogenetic techniques in nine European laboratories in
      relation to chromosomal endpoints induced by three model mutagens.

PMID- 1378200
TI  - Quantitative correlation of mutagenic and carcinogenic potencies for heterocyclic
      amines from cooked foods and additional aromatic amines.
AB  - Aromatic amines have long been recognized as animal and human carcinogens.
      Recently heterocyclic aromatic amines (thermic amines) have been found in small
      amounts in cooked foods, primarily meats, and have proven to be potent mutagens
      and rodent carcinogens. Availability of quantitative databases for mutagenic
      potency in Salmonella and for carcinogenic potency in rodents has made possible a
      study of ten heterocyclic thermic amines and 24 aromatic amines. Potencies on
      mutagenic and carcinogenic scales were significantly correlated. By multiple
      linear regression analysis and multivariate analysis of variance, two descriptive
      structural factors were found to modulate the two modes of biological response.
      These factors were number of rings and methyl substitution at carbon atoms. The
      quantitative correlation between mutagenic and carcinogenic potencies and the
      modulating structural factors suggest a significant similarity of molecular
      mechanisms and support the utility of the short-term bacterial assay in
      evaluating hazard levels.

PMID- 1378201
TI  - Enhanced cytogenetic detection of previous in vivo exposure to mutagens in human
      lymphocytes after treatment with inhibitors of DNA synthesis and DNA repair in
      vitro.
AB  - To increase the sensitivity of cytogenetic surveillance of exposure to mutagens
      in the peripheral lymphocyte assay, structural chromosome aberrations (CA) were
      studied after inhibition of DNA synthesis and DNA repair with hydroxyurea and
      caffeine in culture 3 h prior to harvesting. CA and sister-chromatid exchanges
      (SCE) from conventional cultures from the same subjects were used for comparison.
      Smoking was used as exposure parameter. Thirty-two smokers and 35 nonsmokers were
      studied. In the inhibited cultures a significantly higher number of aberrations
      was found in lymphocytes from smokers than nonsmokers: chromatid breaks (20.4 vs.
      11.8, p = 0.0002), chromosome breaks (4.5 vs. 1.7, p = 0.0003), and the number of
      cells with aberrations (18.9 vs. 12.4, p = 0.0001), when 50 cells per subject
      were analyzed. In conventional cultures no increase in gaps, chromatid and
      chromosome breaks or number of cells with aberrations was found in smokers when
      100 cells from each subject were studied. Smokers showed an increased number of
      SCE (6.8 vs. nonsmokers 5.9, p = 0.02). A significant positive linear correlation
      (r = 0.39, p = 0.01) was seen between SCE and the number of cells with chromatid
      breaks from inhibited cultures. The present results indicate that adding
      hydroxyurea and caffeine to lymphocyte cultures for the last 3 h prior to
      harvesting may enhance the detection of cytogenetic damage from previous in vivo
      exposure to mutagens.

PMID- 1378202
TI  - Repair of DNA damage induced by oxygen radicals in human non-proliferating and
      proliferating lymphocytes.
AB  - Repair of DNA lesions induced by oxygen radicals, generated by xanthine/xanthine
      oxidase (X/XO), was studied in human peripheral blood lymphocytes and in PHA
      stimulated proliferating lymphocytes from 4 healthy subjects. The lesions
      included DNA-strand breaks (SSB) and other lesions that are converted to SSB
      under alkaline conditions. The frequencies of SSB were estimated by fluorometric
      analysis of DNA unwinding. Maximum production of SSB occurred within 10 min of
      incubation with X/XO at 22 degrees C; with 0.5 mM or higher concentrations of
      xanthine; and with 0.1-0.5 units/ml of xanthine oxidase. Proliferating
      lymphocytes repaired X/XO-induced SSB about 4 times more rapidly than
      lymphocytes. Lymphocytes repaired X/XO-induced SSB more slowly than SSB caused by
      gamma-radiation. These findings are consistent with the evidence that a number of
      DNA-repair enzymes have greater activity in proliferating cells than in resting
      cells. These findings also support the view that there are differences between
      the DNA damage due to oxygen radicals and that due to ionizing radiation.

PMID- 1378203
TI  - Radiation-sensitive irs mutants rejoin DNA double-strand breaks with efficiency
      similar to that of parental V79 cells but show altered response to radiation
      induced G2 delay.
AB  - Induction and repair of DNA double-strand breaks (dsb) was investigated in
      plateau phase Chinese hamster V79 cells and three radiosensitive mutant cell
      lines derived from them, irs-1, irs-2 and irs-3, using a pulsed-field gel
      electrophoresis assay, Asymmetric Field Inversion Gel Electrophoresis (AFIGE).
      There was no difference in the induction of DNA dsb per Gy and dalton between the
      radiosensitive mutant cells and wild-type V79 cells despite the wide differences
      in their radiosensitivity. Also, repair of DNA dsb proceeded in all cell lines
      with similar kinetics. In contrast to these observations at the DNA level,
      irradiation of exponentially growing cells showed a prolonged delay in G2 for irs
      2 cells and a shortened delay in G2 for irs-1 cells, as compared to wild-type V79
      cells. These results confirm previous observations suggesting that a deficiency
      in the rejoining of DNA dsb is unlikely to be the cause of the increased
      radiosensitivity of irs cells, and implicate alterations in postirradiation cell
      cycle progression as a possible cause for this phenomenon, although the mechanism
      is not known.

PMID- 1378204
TI  - Excision repair influences the site and strand specificity of sunlight
      mutagenesis in yeast.
AB  - A collection of 384 mutations recovered in a tRNA gene (SUP4-o) following
      exposure of isogenic excision-repair-proficient (RAD1) or deficient (rad1)
      strains of the yeast Saccharomyces cerevisiae to sunlight was characterized by
      DNA sequencing. In each case, greater than 90% of the mutations were single base
      pair substitutions with events at G.C pairs constituting most of the changes.
      However, more than half of these substitutions were transversions in the RAD1
      strain whereas transitions predominated in the rad1 strain. Tandem double
      substitutions were recovered in both strains and the individual changes were
      exclusively G.C----A.T transitions. The majority of single substitutions, and all
      tandem double changes, were at base-pairs where the pyrimidine(s) was part of a
      dipyrimidine sequence and the site specificities were consistent with cyclobutane
      dimers and/or pyrimidine (6-4) pyrimidone photoproducts contributing to sunlight
      mutagenesis. Yet, the data also pointed to an important role for lesions that
      form at G.C pairs and give rise to transversions. Analysis of the strand
      specificity of sunlight mutagenesis indicated that transitions or transversions
      at G.C pairs occurred preferentially in SUP4-o at sites where a dipyrimidine or a
      guanine, respectively, was on the transcribed strand. These biases required a
      functional excision-repair system.

PMID- 1378205
TI  - Spontaneous and ultraviolet-induced mutations on a single-stranded shuttle vector
      transfected into monkey cells.
AB  - The shuttle vector plasmid PCF3A, carrying the supF target gene, can be
      transfected into monkey COS7 cells as single-stranded or double-stranded DNA.
      Single strand-derived plasmid progeny exhibited a 10-fold higher spontaneous
      mutation frequency than double strand-derived progeny. The location of
      spontaneous mutations obtained after transfection of the single-stranded vector
      shared similarities with that for double-stranded vectors. However, the nature of
      base changes was very different. Single-stranded PCF3A DNA was used to study
      ultraviolet-induced mutagenesis. An earlier report (Madzak and Sarasin, J. Mol.
      Biol., 218 (1991) 667-673) showed that single-stranded DNA exhibited a lower
      survival and a higher mutation frequency than double-stranded DNA after
      ultraviolet irradiation. In the present report, sequence analysis of mutant
      plasmids is presented. The use of a single-stranded vector allowed us to show the
      targeting of mutations at putative lesion sites and to determine the exact nature
      of the base implicated in each mutation. Frameshift mutations were more frequent
      after transfection of control or irradiated plasmid as single-stranded DNA than
      as double-stranded DNA. Multiple mutations, observed at a high frequency in the
      spontaneous and ultraviolet-induced mutation spectra following single-stranded
      DNA transfection, could be due to an error-prone polymerisation step acting on a
      single-stranded template.

PMID- 1378207
TI  - Workshop on DNA-repair genes. Held at the 9th International Congress of Radiation
      Research, Toronto, Canada, 7-12 July 1991.

PMID- 1378206
TI  - UV-induced hprt mutations in a UV-sensitive hamster cell line from
      complementation group 3 are biased towards the transcribed strand.
AB  - The molecular nature of 254 nm ultraviolet light (UV)-induced mutations at the
      hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in UV24 Chinese
      hamster ovary (CHO) cells, which are defective in nucleotide excision repair, was
      determined. Sequence analysis of 19 hprt mutants showed that single base
      substitutions (9 mutants) and tandem base changes (7 mutants) dominated the UV
      mutation spectrum in this cell line. Sixty-five percent of the base substitutions
      were GC greater than AT transitions, whereas the rest consisted of transitions
      and transversions at AT base pairs. Analysis of the distribution of dipyrimidine
      sites over the two DNA strands, where the photoproducts causing these mutations
      presumably were formed, showed that 12 out of 14 mutations were located in the
      transcribed strand of the hprt gene. A similar strand distribution of mutagenic
      photoproducts as in UV24 has previously been found in two other UV-sensitive
      Chinese hamster cell lines (V-H1 and UV5), indicating that under defective
      nucleotide excision repair conditions the induction of mutations is strongly
      biased towards lesions in the transcribed strand of the hprt gene. A plausible
      explanation for this phenomenon is that during DNA replication large differences
      exist in the error rate with which DNA polymerase(s) bypass lesions in the
      templates for the leading and lagging strand, respectively.

PMID- 1378208
TI  - Protective effects of ether, oxygen and their mixture for radiation in Drosophila
      melanogaster.
AB  - Protective effects of ether mixed with air or oxygen against ionizing radiation
      damages were demonstrated in adult flies of Drosophila melanogaster. The
      protective effects against knock-down on the 2nd day and lethality on the 8th day
      after irradiation were not affected by the radiation sensitivity and DNA repair
      capacity of the strains. Ether (4.2%) in oxygen was more effective than ether in
      air for both endpoints. The protective effects may be due to damages not
      involving cell division, since no mitotic cells are observed in adult flies
      except in gonadal glands. A change in the orderliness of the cell membrane by
      ether is suggested to be the cause of the protective effects.

PMID- 1378209
TI  - Phenotypes conferred by the Bacillus subtilis recM13 mutation and the din23
      fusion.
AB  - The din23 fusion encodes a B. subtilis SOS-inducible regulatory region fused to
      the E. coli lacZ gene (Love et al., 1985). A strain encoding the din23 fusion and
      a recM13 allele showed low-level constitutive beta-galactosidase expression, was
      induced for beta-galactosidase production by DNA gyrase inhibitors but not by DNA
      damaging agents, and was slightly induced by a variety of agents which do not
      normally induce the SOS regulon. The din23 fusion itself resulted in high levels
      of spontaneous prophage induction in wild-type, recM- and recA-hosts, despite the
      fact that the din23recM13 strain was not induced for beta-galactosidase
      production by DNA-damaging agents. The results suggest that the recM gene may be
      involved with the regulation of the RecA protease-mediated SOS response, while
      the din23 gene may be involved with the regulation of an alternative function
      which results in the cleavage of prophage repressor.

PMID- 1378210
TI  - Absence of strand-specific repair of cyclobutane pyrimidine dimers in active
      genes in Drosophila melanogaster Kc cells.
AB  - Strand-specific excision repair of UV-induced cyclobutane pyrimidine dimers was
      investigated in three genes: Gart, Notch and white in the permanent Kc cell line
      derived from wild-type Drosophila melanogaster embryonic cells. In this cell line
      Gart and Notch are transcriptionally active, whereas white is not expressed.
      Cells were irradiated with 10 or 15 J/m2 ultraviolet (UV) light (predominantly
      254 nm). In all three genes, cyclobutane pyrimidine dimers were removed from the
      non-transcribed strand at the same rate and to the same extent as from the
      transcribed strand, indicating the absence of strand-specific repair in permanent
      Drosophila embryonic cell lines.

PMID- 1378211
TI  - Inhibition of transcription and strand-specific DNA repair by alpha-amanitin in
      Chinese hamster ovary cells.
AB  - Recent studies have shown preferential repair of UV-induced cyclobutane
      pyrimidine dimers (CPD) in the transcribed strand of the expressed dihydrofolate
      reductase (DHFR) gene in human and rodent cells. We have tested the hypothesis
      that the strand-specific repair of such transcription-blocking lesions is
      dependent upon concurrent transcription. Chinese hamster ovary (CHO) B11 cells
      with an amplified DHFR gene were treated with alpha-amanitin before irradiation
      with UV (254 nm) and during post-irradiation incubation. Nuclear run-off analysis
      verified inhibition of transcription in the DHFR gene. CsCl density gradient
      analysis showed that alpha-amanitin at the levels used does not significantly
      interfere with overall genomic repair replication or semiconservative
      replication. However, we did observe a dramatic reduction in the removal of CPD
      from the transcribed strand in the 14 kb KpnI fragment within the DHFR gene in
      treated cells. We conclude that strand-specific repair of an active gene in CHO
      cells is dependent upon the activity of the transcribing RNA polymerase. Our
      results support the model that transcription complexes stalled at CPD signal the
      repair machinery to achieve efficient repair of the transcribed strand in active
      genes.

PMID- 1378212
TI  - Mapping of a B-cell epitope present in the neuraminidase of Trypanosoma cruzi.
AB  - We have previously shown that a polyclonal (rabbit anti-TCNA) and a mouse
      monoclonal antibody (TCN-2) against the neuraminidase of Trypanosoma cruzi (TCNA)
      inhibit enzyme activity, immunoprecipitate active enzyme, enhance in vitro
      infection, and identify a subpopulation of extracellular trypomastigotes. We now
      report on the identification of a synthetic peptide that contains the epitope
      recognized by these antibodies. The synthetic peptide (TR) is a dodecamer (D-S-S
      A-H-G-T-P-S-T-P-A) deduced from the DNA sequence of the long tandem repeat (LTR)
      domain present in the TCNA carboxyterminus. By ELISA, rabbit anti-TCNA bound to
      TR coupled to ovalbumin, and the binding was inhibited by soluble TR but not by
      BR (Y-S-V-D-D-G-E-T-W-E), a peptide derived from the N-terminal domain of the
      enzyme. TCN-2 recognized TR, and this reaction as well as TCN-2 binding to
      endogenous TCNA could be inhibited by soluble TR but not by BR. These results
      indicate that the rabbit anti-TCNA and TCN-2 react with the LTR region of TCNA.
      Antibodies to TR reacted by immunoblot with the TCNA of the Silvio X-10/4, MV-13
      and Y-H6 strains, identifying the same molecular polymorphism previously observed
      with the rabbit anti-TCNA and TCN-2. Furthermore, anti-TR antibodies
      immunoprecipitated active enzyme and immunofluorescence analysis revealed that
      anti-TR and TCN-2 antibodies detected equally well the differential expression of
      their epitopes in intra- and extracellular trypomastigotes. Moreover, expression
      of TR and TCN-2 epitopes on the different stages of T. cruzi paralleled the stage
      specificity of TCNA activity. TCN-2 prevented desialylation by TCNA of intact
      cells but not of soluble glycoconjugates, indicating that TCN-2 epitope is
      probably not associated with the enzyme catalytic site, in agreement with the
      predicted sequence of the TCNA gene. Finally, analysis of the humoral response of
      a Chagasic patient to different areas of the TCNA molecule indicated that the
      antibody response is predominantly against TR suggesting that the tandem repeat
      is the immunodominant domain of TCNA.

PMID- 1378213
TI  - Labelling and recording from dissociated target-specific rat superior cervical
      ganglion neurons.
AB  - A population of neurons was retrogradely labelled in the superior cervical
      ganglia (SCG) of the adult rat following the injection of the fluorescent dye
      Fast blue into the submandibular salivary glands (SMG). The neurons retained the
      fluorescent label following dissociation and culture. Electrical and
      chemosensitive properties of the labelled neurons were studied with the whole
      cell patch-clamp technique.

PMID- 1378214
TI  - Isolation and identification from Salvia officinalis of two diterpenes which
      inhibit t-butylbicyclophosphoro[35S]thionate binding to chloride channel of rat
      cerebrocortical membranes in vitro.
AB  - Ethanolic extracts from dried leaves of sage (Salvia officinalis) showed
      inhibition of [35S]tertiary-butylbicyclophosphorothionate ([35S]TBPS) binding to
      rat brain membranes in vitro. This ligand is considered to bind to the chloride
      channel of the GABA/benzodiazepine receptor complex in brain tissue. Substances
      having inhibitory activity were purified and their chemical structure identified
      as the diterpenes carnosic acid and carnosol (IC50 values of 33 +/- 3 microM and
      57 +/- 4 microM, respectively). The two compounds did not affect binding of the
      ligands [3H]muscimol and [3H]diazepam to the GABA/benzodiazepine complex in
      vitro. Saturation experiments of [35S]TBPS binding indicated that carnosic acid
      decreases the binding affinity.

PMID- 1378215
TI  - Young CA1 pyramidal cells of rats, but not dentate gyrus granule cells, express a
      delayed inward rectifying current with properties of IQ.
AB  - In hippocampal CA1 pyramidal cells (CA1PC) and dentate gyrus granule cells (DGGC)
      we compared the expression of currents which could cause differences in discharge
      behaviour. Negative current injections cause a uniform hyperpolarization in DGGC
      whereas in CA1PC the initial hyperpolarization is followed by a repolarization
      towards resting membrane potential. The underlying inward current can be
      classified as IQ. It is sensitive to CsCl, activated at -80 mV, and it has a mean
      amplitude of -109.8 pA and a mean activation time constant of 187 ms with voltage
      jumps from -40 to -120 mV. We conclude that some of the differences in response
      properties of DGGC and CA1PC upon repetitive stimulation can be attributed to
      differences in the expression of IQ.

PMID- 1378217
TI  - A sexually dimorphic population of galanin-like neurons in the rat lumbar spinal
      cord: functional implications.
AB  - The rat lumbar spinal cord contains a population of galanin- and cholecystokinin
      containing neurons which are located dorsolateral to the central canal and
      project to the thalamus. New data are presented herein which reveal that the
      number of these neurons, as shown by galanin-like immunostaining, is sexually
      dimorphic with males containing 62% more of these neurons than females. This is
      the first demonstration of a sexually dimorphic population of intraspinal neurons
      which projects to higher CNS centers rather than to peripheral targets.

PMID- 1378216
TI  - NMDA treatment and K(+)-induced depolarization selectively promote the expression
      of an NMDA-preferring class of the ionotropic glutamate receptors in cerebellar
      granule neurones.
AB  - Growth conditions which promote the survival of cerebellar granule cells in
      culture, such as high K+ or N-methyl-D-aspartate (NMDA) treatment, also promote
      the functional expression of an NMDA-preferring subtype alone of the ionotropic
      glutamate receptors. The selective regulation of NMDA receptors detected
      electrophysiologically in individual cells, using the whole cell patch clamp
      technique, is characteristic of granule cells in general: NMDA-induced 45Ca2+
      influx increased several-fold in cultures treated with either high K+ or NMDA.
      The increase in NMDA receptor activity was correlated with an increase in the
      expression of an NMDA receptor protein. Since the effect of these 'trophic'
      conditions is mediated through Ca2+, the induced increase in the density of NMDA
      receptors (which gate a Ca2+ conductance) provides a positive feedback for
      strengthening the trophic influences.

PMID- 1378218
TI  - Nitric oxide may act as a messenger between dorsal root ganglion neurones and
      their satellite cells.
AB  - The distribution of NADPH-diaphorase and cyclic GMP in neonatal dorsal root
      ganglia in vitro has been investigated under control conditions and in response
      to incubation with either sodium nitroprusside or N-methyl-D-aspartate. NADPH
      diaphorase activity which reveals the distribution of nitric oxide (NO) synthase
      in neurons was found to be intense in some dorsal root ganglion neurones and
      present at a lower level in the majority. Basal levels of cGMP were found to be
      low but when stimulated by sodium nitroprusside were found to be selectively
      increased in satellite cells. The results suggest that NO may function as a
      signalling system between neurones and satellite cells in sensory ganglia.

PMID- 1378219
TI  - Regulation of rodent myelin proteolipid protein gene expression.
AB  - The regulation of rodent proteolipid protein (PLP) gene expression was studied
      during rat development and in cultured cells. Nuclear run-on assays demonstrate a
      strong transcriptional component associated with the developmental regulation of
      the PLP mRNA. Transcription rates of the PLP and MBP genes parallel their
      respective steady-state mRNA levels throughout rat brain development. In
      addition, a moderate 25-h half-life was measured for PLP mRNA in 37-day-old
      cultured oligodendrocytes, suggesting that regulation of PLP expression occurs
      predominantly at the transcriptional level. Finally, 5400 and 1400 bp of mouse
      PLP 5'-flanking sequence demonstrate transcriptional activity 13-fold and 5-fold
      above background, respectively, in hamster glial cells. Far upstream elements are
      clearly involved in transcription of the PLP gene. The 5400 bp sequence
      demonstrates no more activity than the 1400 bp in a mouse hepatoma cell line
      suggesting that elements involved in the glial cell-specific expression of PLP
      lie between 1400 and 5400 bp upstream of the gene.

PMID- 1378220
TI  - Nicotine- and capsaicin-, but not potassium-evoked CGP-release from cultured
      guinea-pig spinal ganglia is inhibited by Ruthenium red.
AB  - In the present study we have investigated the effects of nicotine, capsaicin,
      potassium, glutamate and aspartate on release of calcitonin gene-related peptide
      (CGRP)-like immunoreactivity (-LI) from guinea-pig dorsal root ganglion (DRG)
      cultures. In addition the possible influence of Ruthenium red (RR), neuropeptide
      Y (NPY) and noradrenaline (NA) on the CGRP-LI outflow has been evaluated.
      Nicotine, capsaicin and potassium, but not glutamate or aspartate, evoked a
      Ca(2+)-dependent increase in the culture medium, suggesting release of CGRP-LI.
      RR inhibited the effect of both capsaicin and nicotine but did not influence
      potassium-induced CGRP-LI release. Furthermore, the nicotine- but not capsaicin
      evoked CGRP-LI release was inhibited by NPY. It is concluded that DRG cultures
      represent an experimental model where regulation of CGRP-LI release can be
      studied. The ability of RR to inhibit not only capsaicin but also nicotine
      effects indicate that the proposed selectivity of RR may depend on the agent used
      to evoke peptide release and/or concentrations used.

PMID- 1378222
TI  - [Role of the hypothalamo-hypophyseal neurosecretory system in the accomplishment
      of the antistress effect of substance P].
AB  - Light and electron microscopy and spectrophotometry were employed in study of the
      morphofunctional condition of the hypothalamo-hypophyseal neurosecretory system
      (HHNS) of intact rats after exposure to stress in injection of substance P.
      Injection of 12.5 mcg/100g of substance P decelerates the outflow of the
      neurosecretory substance in intact animals and inhibits the processes of
      biosynthesis in the neurocytes of the hypothalamic supraoptic nucleus. Injection
      of substance P prior to exposure of the organism to the stress effects leads to
      diminution of the HHNS response of them and prevents the development of
      dystrophic changes in the gastric mucosa.

PMID- 1378221
TI  - Evidence that pharmacological manipulations of central L-arginine-NO pathway
      influence blood pressure and heart rate in rats.
AB  - In the present study we have investigated whether pharmacological manipulations
      of central L-arginine-nitric oxide (L-Arg-NO) pathway could affect blood pressure
      (BP) and heart rate (HR) in normotensive rats either untreated or pretreated with
      E. coli lipopolysaccharide (LPS). The intracerebroventricular injection (i.c.v.)
      of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis,
      caused a fall of BP and HR in LPS-treated but not in control rats. Furthermore,
      the pressor responses to i.c.v. injection of N-methyl-D-aspartate (NMDA) were
      enhanced by L-Arg or LPS treatment and, in both cases, this potentiation was
      blocked by L-NAME. The present results show that in some experimental conditions,
      such as activation of NMDA receptors or LPS pretreatment, the central
      microinfusion of drugs affecting the L-Arg-NO pathway may interfere with BP and
      HR.

PMID- 1378223
TI  - Am I ethical? How do I know?

PMID- 1378224
TI  - Prediction of response to adjuvant chemotherapy in premenopausal lymph node
      positive breast cancer patients with morphometry, DNA flow cytometry and HER
      2/neu oncoprotein expression. Preliminary results.
AB  - The value of morphometry, DNA flow cytometry and HER-2/neu oncoprotein expression
      for prediction of response to adjuvant chemotherapy in premenopausal lymph node
      positive breast cancer patients was evaluated in a group of CMF treated patients
      and controls with long-term follow-up. In the treated group, the Morphometric
      Prognostic Index (cutpoint 1.1) was the best prognosticator (p less than 0.0001,
      MC = 16.9), followed by the Mitotic Activity Index, the volume percentage
      epithelium and the number of positive nodes. For the controls, only the % HER
      2/neu oncoprotein expression revealed significant differences (p less than
      0.0001, MC = 16.3). When directly comparing treated patients and controls
      stratified for a certain parameter, no significant differences were obtained,
      although a trend towards improved survival in the treated group was present for
      some of the subgroups for several parameters. These preliminary results indicate
      that morphometric features and quantitative HER-2/neu oncoprotein expression may
      be important factors for identifying cases that will or will not respond to
      adjuvant chemotherapy.

PMID- 1378225
TI  - X-ray induction of micronuclei in human lymphocyte subpopulations differentiated
      by immunoperoxidase staining.
AB  - In this study we sought to confirm the radiosensitivity of human peripheral blood
      lymphocyte subpopulations using a micronucleus assay. Mononucleated cells
      isolated from peripheral blood were irradiated with X rays. After being cultured
      for 3 days, cells were fixed and stained using the immunoperoxidase staining
      technique. Lymphocyte subpopulations were characterized by means of the
      monoclonal antibodies Leu4 (CD3), Leu2a (CD8) and Leu19 (CD56). Dose-response
      curves were obtained by scoring the number of micronuclei in binucleated cells
      that reacted with a specific antibody and were then stained. The dose response of
      CD8+ (suppressor/cytotoxic) cells was quite similar to that of CD3+ (pan T)
      cells. In comparison, CD56+ (natural killer) cells were significantly less
      sensitive, although scorable binucleated CD56+ cells made up less than 4% of the
      total number of binucleated cells.

PMID- 1378226
TI  - Antiribosomal antibodies in systemic lupus erythematosus.
AB  - ARA occur in approximately 10% of randomly selected SLE patients but in up to 40%
      of patients with active disease. Anti-P antibodies appear to be a highly specific
      diagnostic marker for SLE because they are rarely detected in other multisystem
      autoimmune disorders. ARA are most frequently directed against the P proteins,
      and the shared conserved C-terminus of the P proteins is immunodominant in almost
      all sera tested. Anti-P antibodies increase in titer in patients with active
      disease and have been reported to be detected more frequently in patients with
      severe behavioral disturbances. This may be particularly true of patients with
      affective disorders. The clinical utility of serologic tests for anti-P in
      central nervous system lupus must await large, prospective studies. Other ARA
      antibodies have been detected in patients with SLE. These antibodies include anti
      28S rRNA, anti-S10, and anti-L12. In all cases, the frequency with which these
      antibodies are detected is increased in sera containing anti-P. The P proteins
      and the 28S rRNA epitope play essential, but as yet undefined, roles in GTPase
      activity on the ribosome. The L12 protein is the mammalian homologue of the E.
      coli and yeast proteins known to bind to the 28S rRNA epitope. These findings
      indicate that some SLE patients produce autoantibodies against multiple
      components of a functionally related domain of the ribosome. This, in turn,
      supports the notion that the ribosome initiates and/or maintains autoantibody
      production. Despite these findings, attempts to induce anti-P antibodies by
      immunization with autologous ribosomes in the autoimmune strain of mouse, MRL,
      have been unsuccessful. It therefore seems likely that the ribosomal components
      must be altered to break tolerance or that other abnormalities of the immune
      system are necessary for autoantibody production.

PMID- 1378228
TI  - [Subjectivity and objectivity in transperineal biopsy and transrectal prostatic
      aspiration cytology].
AB  - Transperineal biopsy (TPB) together with transrectal aspirative cytology (TRAC)
      was performed in 50 prostates, 28 carcinomas and 22 no malignant pathologies.
      Both techniques were compared both objectively as subjectively. With TPB in 3.5%
      of carcinomas and in 13.6% of benign pathologies not enough sampling material was
      obtained to perform the diagnoses. With TRAC these figures were respectively 3.5%
      and 9%. With the viable samples TPB sensibility was 100% being TRAC 96.3%.
      Specificity was 100% for both techniques. With TPB, 40% of the biopsies labelled
      as "dubious obtention of enough material to perform diagnoses", were finally
      insufficient; on TRAC this rate was 11%. In the three cases of insufficient
      sampling material with TRAC only aspirative punction had been performed. We think
      it is necessary to perform more than one punction in TRAC. TRAC is, for its lack
      of complications, efficacy, and because it is easy to perform, the preferred
      technique versus TPB.

PMID- 1378227
TI  - Autoantibodies in polymyositis.
AB  - A group of autoantibodies have been identified that are found almost exclusively
      in patients with polymyositis and dermatomyositis (myositis-specific antibodies).
      Most have been associated with characteristic clinical subgroups. Five of the
      myositis-specific antibodies are directed at aminoacyl-tRNA synthetases and have
      been associated with a similar clinical syndrome marked by myositis, interstitial
      lung disease, arthritis, and Raynaud's phenomenon (antisynthetase syndrome).
      Myositis-specific antibodies can help with patient diagnosis, subgroup
      classification, and possible prognosis. Their role in the pathogenesis of
      myositis remains to be defined, but their production is genetically influenced
      and appears to be linked to fundamental etiologic factors.

PMID- 1378229
TI  - Sodium nitroprusside increases cyclic GMP in fetal rat bone cells and inhibits
      resorption of fetal rat limb bones.
AB  - To elucidate the role of cGMP in bone resorption, the nucleotide was measured in
      bone and bone cells in response to several agents including stimulators of bone
      resorption. In other experiments, sodium nitroprusside (SNP), which elevates bone
      cGMP, was tested for effects on resorption. In cells from 20-day fetal rat
      calvaria, cGMP was 52.4 +/- 8.4 fmol/10(6) cells; cAMP was 5.3 +/- 0.3 pmol/10(6)
      cells. SNP, 0.1 mM, in the presence of IBMX, increased cGMP 74% with no
      significant effect on cAMP. Parathyroid hormone (PTH), 0.5 microM, did not
      significantly affect cGMP, but increased cAMP 711%. Calcitriol did not affect
      either nucleotide. In bone resorption studies, 0.1 mM SNP inhibited the effects
      of PTH and calcitriol. Lower concentrations of SNP (0.001, 0.01 mM) had no
      effects on hormone-stimulated resorption. Unstimulated control bones were not
      affected by 1 nM-1 mM SNP. The results suggest that elevated cGMP could result in
      inhibition of bone resorption.

PMID- 1378230
TI  - A new restriction fragment length polymorphism of the human alpha-fetoprotein
      gene in Japanese individuals: detection of loss of heterozygosity in human
      hepatocellular carcinoma.
AB  - By using the cDNA probe for the human alpha-fetoprotein (AFP) gene, one
      restriction fragment length polymorphism (RFLP) was discovered in Japanese
      patients. A variety of combinations of restriction enzymes and probes were
      evaluated in DNA samples from 25 Japanese individuals who were genetically
      unrelated. As a result, AvaII identified one invariant band of 8 kb and
      polymorphic bands at either 2.8 or 2.0 kb with the 5'-region probe from a cDNA
      clone, pHAF7. With the AvaII/pHAF7 combination, we examined the loss of
      heterozygosity in 14 patients with hepatocellular carcinoma (HCC). Of 6
      informative specimens, 2 showed loss of heterozygosity. These data suggest that
      the AFP cDNA probe could be useful for analyzing loss of heterozygosity on
      chromosome 4q in human HCC.

PMID- 1378231
TI  - Plasma levels of vasoactive regulatory peptides in patients receiving regular
      hemodialysis treatment.
AB  - The fasting plasma levels of 10 vasoactive regulatory peptides were measured by
      radioimmunoassay in 23 stable patients with chronic renal failure receiving
      regular hemodialysis treatment (RDT) and compared with those of healthy controls.
      The plasma concentrations of arginine vasopressin, atrial natriuretic peptide,
      beta-endorphin, methionine-enkephalin, motilin, neuropeptide Y, substance P, and
      vasoactive intestinal peptide were increased. The plasma level of calcitonin gene
      related peptide was not statistically different from that of the controls. The
      plasma concentration of gamma 2-melanocyte-stimulating hormone was lowered in the
      RDT-patients. The arterial blood pressure correlated with the plasma levels of
      motilin and neuropeptide Y. We conclude that patients with chronic renal failure
      receiving RDT have increased concentrations of 8 out of 10 measured vasoactive
      regulatory peptides. The elevated levels of vasoactive peptides may contribute to
      the adaptation of the cardiovascular system to impaired renal function.

PMID- 1378232
TI  - Long term complications of the intraprostatic spiral. Case report.
AB  - A 76-year-old man had an intraprostatic spiral inserted to relieve bladder outlet
      obstruction that was caused by benign prostatic hypertrophy. After 30 months
      numerous complications had arisen including severe encrustations, urethral
      stricture, and sclerosis of the bladder neck. Regular replacement of the spiral
      or close monitoring of the development of encrustations seem necessary. The
      distal tip and the plating of the spiral require improvement.

PMID- 1378233
TI  - Immunoreactivity, epitope mapping and protection studies with anti-conotoxin GI
      sera and various conotoxins.
AB  - Goat or rabbit anti-conotoxin GI sera recognized native or dithiothreitol-reduced
      alpha-conotoxins GI, MI and SI in an enzyme-linked immunosorbent assay (ELISA).
      Native mu-conotoxin GIIIA or omega-conotoxin GVIA did not react with either anti
      conotoxin GI serum in the assay. The goat anti-conotoxin GI serum neutralized 2.5
      LD50S of alpha-conotoxins GI or MI in mouse lethal assays, while the rabbit
      antiserum had little protective capabilities. Epitope mapping of synthesized
      conotoxin peptide fragments revealed that both anti-conotoxin GI sera recognized
      linear sequences from five different alpha-conotoxins: GI, GIA, GII, MI and SI.
      The CCNPAC sequence was optimally recognized by both antisera.

PMID- 1378234
TI  - Variation in the antigenic characteristics of venom from the Mojave rattlesnake
      (Crotalus scutulatus scutulatus).
AB  - Venoms from 31 specimens of the Mojave rattlesnake (Crotalus scutulatus
      scutulatus) were examined to further characterize reported differences among
      venoms of this species. Twenty-two venoms were recognized by a monoclonal
      antibody to Mojave toxin, CSS12. Nine venoms were recognized by CA-P-8, a
      monoclonal antibody produced against the hemorrhagic venom of C. atrox. Seven of
      these produced strong hemorrhage in mice and were also recognized by polyclonal
      antibodies (anti-F5) produced against a fraction of Mojave rattlesnake venom that
      inactivates serum complement. Fractionated venom revealed that CA-P-8 and anti-F5
      recognized different proteins. Two of the venoms recognized by CA-P-8 were not
      recognized by anti-F5 and produced minimal hemorrhage in mice. This suggests that
      more than one factor may be necessary to induce strong hemorrhage.

PMID- 1378235
TI  - Effects of FK506 on rat thymic epithelial cells; immunohistochemical study.
AB  - The effects of FK506, a new immunosuppressive agent, on the rat thymus were
      investigated using the immunoperoxidase technique and flow cytofluorometry using
      monoclonal antibodies. Flow cytometric analysis of the thymus revealed that the
      proportion of cells labelled positively with OX7 (Thy-1 antigen), OX8 (CD8, T
      cytotoxic/suppressor cells) and W3/25 (CD4, T helper cells and macrophages)
      increased following treatment, with FK506, 1 mg/kg body weight for 14 days. A
      marked reduction of the thymic medulla following treatment was clearly
      demonstrated by staining with OX18 (MHC class I) and OX6 (MHC class II). Changes
      produced by FK506 were also observed in the cortical area of the thymus, being
      especially marked in the subcapsular area and around the blood vessels by
      staining with OX6, PKK-1 (alpha-cytokeratin), AB-1040 (type IV collagen), and AB
      1220 (laminin). Eventually FK506 treatment resulted in patchy reduction of OX-6,
      PKK-1, AB-1040 and AB-1220 positive area in the cortex. This evidence suggests
      that FK506 may impair the thymic microenvironment and subsequently disturb the
      thymocyte maturation.

PMID- 1378236
TI  - Inhibition of the classical activation pathway of complement-mediated lysis by
      monoclonal antibodies to complement components C3c and C3d.
AB  - Eight epitope-mapped monoclonal antibodies (MoAbs) to complement component C3d
      and five to complement component C3c were investigated to determine whether they
      could inhibit the classical activation pathway of complement-mediated lysis (CML)
      by using blood group AB red cells sensitized by A or B MoAbs. Three IgM C3d MoAbs
      and one IgG1 C3c MoAb were able to inhibit CML in a dose-dependent manner. In the
      presence of excess complement, no inhibition was observed. The greatest
      inhibition was observed with two high-affinity IgM antibodies that were specific
      for epitope 1 on the C3d component. Some inhibition was observed with a high
      affinity IgM antibody specific for epitope 3 of the C3d component and also with a
      lower-affinity IgG antibody specific for epitope 1 of the C3c component. The
      results indicate that some complement MoAbs have the capacity to distinguish
      between conformationally and/or functionally different forms of red cell-bound
      C3.

PMID- 1378237
TI  - Distinct hemagglutinin and neuraminidase epitopes involved in antigenic variation
      of recent human parainfluenza virus type 2 isolates.
AB  - A panel of fourteen neutralizing anti-HN monoclonal antibodies (mAbs) to the
      prototype Greer strain of human parainfluenza virus type 2 (PI2) was used to
      determine the extent of antigenic variation in recent virus isolates. Competitive
      binding analysis with the mAbs indicated the presence of at least five distinct
      antigenic sites (I to V) on the HN glycoprotein molecule. MAbs recognizing
      different antigenic sites were found to be associated with the hemagglutinin
      (sites I, IV and V), hemagglutinin and neuraminidase (site II), or neuraminidase
      (site III) activities. The location of two distinct epitopes identifying the
      neuraminidase sites (II and III) was further verified from the generation of
      escape mutants. Antibodies directed to sites I and III failed to show any
      detectable binding or neutralizing activity against a number of natural PI2 virus
      isolates collected in Texas between 1986 and 1987. Interestingly, these natural
      variants, unlike the prototype virus, did not show any detectable neuraminidase
      activity with fetuin as a substrate and the enzyme activity was only detected
      with N-acetylneuramin-lactose as an alternative substrate. Despite the observed
      variation in the antigenic sites, primary infection with the prototype virus or
      the natural variants generated a protective immune response against challenge
      infection with the other virus strains.

PMID- 1378238
TI  - Sendai virus M protein is found in two distinct isoforms defined by monoclonal
      antibodies.
AB  - The use of a monoclonal antibody defines a subset of Sendai virus M protein
      representing about 30% of total. This M protein acquires, during the hour
      following synthesis, an epitope not present on the bulk of M. This epitope
      maturation is observed in acutely as well as in persistently infected cells. It
      takes place in vivo in absence of other viral proteins, but it is not observed
      when the protein is synthesized in a reticulocyte lysate. Epitope maturation does
      not appear to result from phosphorylation, acylation or disulfide bond formation.
      If immunofluorescent staining seems to indicate a preferential association of
      this subset of M protein with nucleocapsids, this is not confirmed by immunogold
      staining or by nucleocapsid isolation. Incubation of cytoplasmic extracts or of
      purified M protein in conditions which do not favor M to M protein association
      results in a relative increase of M protein carrying the maturing epitope. It is
      concluded that M protein exists in two distinct isoforms.

PMID- 1378239
TI  - From records to self-description: the role played by RNA in early evolutive
      systems.
AB  - We study the appearance of genetic information starting from a system where self
      reproductive and enzymatic functions are supported by the same sort of molecules.
      In a first phase, the information must have arisen in the form of rate
      independent sequences as records of enzymatic functions. Although this stage must
      have played an important role in evolution, it will be shown how its evolutive
      capacities were blocked by the impossibility of appearance of geno/phenotype
      duality. Finally, a logical scheme is proposed for a transition process toward a
      system with a code offering a simplification of the conditions required from the
      assumption of a maximum use of the double RNA capacity, both reproductive and
      enzymatic.

PMID- 1378240
TI  - Influence of chromatin molecular changes on RNA synthesis during embryonic
      development.
AB  - Two aspects of the chromatin repeat length (rl) are discussed: (i) Why is rl
      longer for slowly dividing cells than in rapidly dividing cells?, and (ii) Why is
      the temporal evolution of rl a decreasing function of time (t) in mammalian
      cortical neurons, whereas it is an increasing function of t for granule cells
      around the time of birth? These questions are discussed in terms of a hypothesis
      which assumes a correlation between deoxyribonucleic acid (DNA) packaging,
      transcription, and replication.

PMID- 1378241
TI  - Differences in the prevalence of hypertension by ethnic origin and age at
      immigration in a cohort of 5,146 Israelis.
AB  - Marked ethnic differences in hypertension prevalence have been described in
      Jewish immigrants to Israel. The extent to which this phenomenon has persisted
      after a long period of living in the same country, and whether native-born
      descendants exhibit similar patterns, is not clear. The aim of this study was to
      determine the prevalence of hypertension in immigrants to Israel and native-born
      Israelis by region of origin and age at immigration. Complete data were available
      for 5,146 subjects (3,607 men and 1,539 women) aged 20-64 years who were employed
      in Israeli industries and were examined during 1985-1987. In both sexes, Jews
      originating in the West (Europe and the Americas) had higher blood pressures and
      a significantly higher prevalence of hypertension than those from northern Africa
      or Asia, particularly in the age group 20-44 years (17% vs. 9% and 8% in men,
      respectively, and 9% vs. 3% and 5% in women). There was a significant positive
      association between the prevalence of hypertension and age at immigration (p less
      than 0.001) in both sexes, and this finding was present in all ethnic groups. In
      multiple logistic regression analysis, the associations of hypertension with
      ethnic origin and age at immigration were only partly explained by variations in
      body mass index, after controlling for other potentially confounding variables.
      These findings suggest that despite these subjects' having shared a relatively
      similar physical environment for many years, ethnic differences in the prevalence
      of hypertension persist. Immigration at an older age was associated with a higher
      prevalence of hypertension for both subjects originating in industrialized
      countries and those originating in nonindustrialized countries, suggesting that
      the process of immigration itself may adversely affect blood pressure.

PMID- 1378242
TI  - Re: "Invited commentary: how much retropsychology?".

PMID- 1378243
TI  - Carcinoma of the body and tail of the pancreas.
AB  - Recently, several institutions have reported improved results in the treatment of
      patients with carcinoma of the head of the pancreas. In an attempt to determine
      whether similar trends could be demonstrated for patients with carcinoma of the
      body and tail of the pancreas, the records of all 113 patients with an
      adenocarcinoma of the body or tail of the pancreas treated at The Johns Hopkins
      Hospital between 1972 and 1989 were reviewed. The patients were divided into two
      groups: those diagnosed between 1972 and 1982 (41 patients) and those between
      1983 and 1989 (72 patients). No significant differences in tumor stage were
      observed between the two groups. The proportion of patients who underwent surgery
      decreased from 68% to 47% (p = 0.02). The number of patients who had bypass
      operations (15% versus 17%) or pancreatic resection (5% versus 10%) was similar
      in the two groups, but the proportion of patients who underwent exploratory
      laparotomy with biopsy only decreased from 49% to 21% (p = 0.002). The
      postoperative 30-day mortality (7% versus 3%), postoperative morbidity (18%
      versus 21%), median survival (4 months versus 3 months), and the 1-year survival
      (8% versus 9%) did not differ significantly between the two groups. One patient
      survived for 6 years after resection, and another patient is still alive 3 years
      after resection. Thus, unlike adenocarcinoma of the head of the pancreas, it
      appears that treatment results for patients with adenocarcinoma of the body or
      tail of the pancreas have not improved in recent years, the only change being a
      decreased need for exploratory laparotomy with biopsy only.

PMID- 1378244
TI  - Age-related occurrence of signs and symptoms in the Rett syndrome.
AB  - The occurrence of signs and symptoms in the Rett syndrome (RS) was analyzed in a
      series of females born 1945-87 (median age 17 1/2 years) and fulfilling the
      diagnostic criteria for classic RS. For general information, data from 91 girls
      and women were used (group A), while the more detailed analyses were based on
      three age related subgroups: the youngest 20, born 1980-87 (group B); the 34
      girls born 1970-79 (group C); and the oldest 37, born 1945-69 (group D). Data
      from group A indicated a developmental stagnation (stage I) at median age 11 (5
      24) months and loss of ability to use acquired skills (stage II) at 19 (12-36)
      months. Group B displayed subtle prodromes in the first months of life, and later
      in infancy gross motor delay with insufficient equilibrium control. Development
      invariably came to a definite break at a crucial stage of maturation and was
      followed by a remarkable "awakening" and return of interest to act and interact
      (stage III). Loss of skills belonged to the triad contact/communication, hand
      use/skill, and babble/words. By age 2 1/2 years, apraxia and involuntary and
      stereotyped movements, were found in all. Seizures, hyperventilation and spells
      of screams and laughter were more frequent in group C (94%, 65% and 71%,
      respectively), and breathholding, bloating and drooling in group D (73%, 43% and
      81%, respectively). Plantar flexion and abiotrophy of feet, as well as peroneal
      weakness and scoliosis, increased with age and was found in 89%, 86%, and 89%,
      respectively. The sequence of events described, emerged as subtle insufficiency
      and more or less abruptly turned into loss. Conversely to known progressive
      encephalopathies, the deterioration was followed by excess of activity, only
      years later to turn into restriction.

PMID- 1378245
TI  - Low CSF HVA levels in the Rett syndrome: a reflection of restricted synapse
      formation?
AB  - The concentration of neurotransmitter metabolites in the CSF was determined in 10
      girls with the Rett syndrome (RS) (age range 5.8-17.2) and in 14 control children
      (age range 4.5-16.7) treated for acute leukemia without signs of CNS involvement.
      Homovanillic acid concentration decreased with age in both groups. The decrease
      was less steep in RS compared to controls, with lower concentrations in young
      girls and normal concentrations at 15 years of age. 5-hydroxyindoleacetic acid
      decreased proportionally in both groups. It is suggested that the low
      concentration of HVA in young girls reflect deficient multiplication of
      catecholaminergic synapsis.

PMID- 1378246
TI  - Microcorrosion casts of hamster luteal and follicular vasculature throughout the
      estrous cycle.
AB  - Golden hamster (Mesocricetus auratus) ovarian microcorrosion casts were studied
      as a model system to analyze angiogenesis that occurs in the corpus luteum (CL)
      during the estrous cycle. Growth of the vasculature in the hamster CL occurs
      rapidly with complete formation and subsequent degeneration occurring during the
      4-day estrous cycle. This study followed the growth of these vessels by casting
      the ovarian vasculature at 4-hour intervals during the formation of the CL,
      viewing the casts on a Scanning Electron Microscope (SEM), and comparing the
      consecutive casts. This study revealed that the microvasculature of the CL forms
      rapidly from the vessels of the theca folliculi of newly ruptured follicles and
      that this growth is in an internal direction. This method of casting, when used
      in conjunction with the high magnification provided by the Hitachi field emission
      high resolution SEM, enabled us to analyze the growing tips of the vascular
      sprouts. The vasculature of the CL grows throughout day 1 and well into day 2 of
      the cycle. Flat veins, characteristic of the external surface of a mature CL,
      formed by the afternoon of day 2. Obvious degeneration of the vasculature of the
      CL took place throughout day 3. This study provided a detailed description of the
      angiogenesis that occurred throughout the rapid formation of the hamster CL and
      showed that this method produced casts of suitable quality for experimental
      observations.

PMID- 1378248
TI  - Balloon dilation of postoperative persistent coarctation of aorta and valvular
      aortic stenosis--a case report.
AB  - Coarctation of aorta is frequently associated with severe valvular aortic
      stenosis. The authors report a case of severe, persistent postoperative
      coarctation of aorta and severe aortic stenosis who was given successful
      palliative treatment with percutaneous balloon dilation of both sites of
      obstruction. This is, to the best of their knowledge, the first report of such an
      intervention in this group of patients.

PMID- 1378247
TI  - [t-PA and PAI in patients with Raynaud's syndrome in treatment with a stable
      prostacyclin analog].
AB  - An study was made in order to determinate the relationship between the
      restoration of the local fibrinolytic activity and the clinical signs in patients
      with a Raynaud's phenomenon. It is known that local fibrinolytic activity is a
      system influenced by changes into its components produced by exogenous and
      endogenous factors. An important role is represented by the t-PA and PAI-1. On
      the contrary, u-PA doesn't change. Samples were all taken at the same time,
      approximately at the middle of the morning. In patients with Raynaud's phenomenon
      treated with a prostacyclin stable analogous, we have perceived a clinical
      improvement, corresponding with a fibrinolytic activity increase.

PMID- 1378249
TI  - Anti-equine tumor necrosis factor (TNF) activity of antisera raised against human
      TNF-alpha and peptide segments of human TNF-alpha.
AB  - Antisera raised in rabbits against either purified recombinant-derived human
      tumor necrosis factor (TNF)- alpha (huTNF) or huTNF peptide-bovine thyroglobulin
      conjugates were evaluated for anti-equine TNF (eqTNF) activity. Binding and
      neutralizing anti-eqTNF activities were found in antisera raised against whole
      huTNF or against either of the peptides containing the N-terminal 15 amino acids
      of huTNF (huTNF[1-15] and huTNF[1-31]). Anti-eqTNF activity was not detected in
      antisera raised against huTNF[65-79], huTNF[98-111] or huTNF[124-141] peptides.
      The addition of excess huTNF[1-15] completely inhibited the ability of anti
      huTNF[1-15] to bind eqTNF and reduced by approximately 25% the anti-eqTNF
      activity of an antiserum raised against whole huTNF. Nonconjugated huTNF[1-15]
      did not have eqTNF agonist or antagonist activity. Results were consistent with
      previous structural and functional data implicating the N-terminus of huTNF in
      receptor binding and indicate that the homologue of huTNF[1-15] on eqTNF may be a
      potentially important target for neutralizing anti-eqTNF antibodies.

PMID- 1378250
TI  - Comparison of antibody responses in cattle to outer membrane proteins from
      Pasteurella haemolytica serotype 1 and from eight untypeable strains.
AB  - Membrane associated proteins from 8 untypeable Pasteurella haemolytica strains
      were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      compared with those of P haemolytica serotypes 1 and 2. Cattle antisera obtained
      from P haemolytica serotype 1 vaccine trials were used in immunoblotting assays
      to compare the membrane proteins from the 8 untypeable strains with those from P
      haemolytica serotypes 1 and 2. Densitometry was used to identify bands, and using
      linear regression analyses, the peak area optical densities (measuring antibody
      response) were correlated to lesion scores from the vaccinated calves.
      Significant antibody responses to proteins of 99, 69, 60, 55, 47, 45, 39, 33, 30,
      16, and 14.5 kDa were detected for 4 or more of the 8 P haemolytica untypeable
      strains. Serotypes 1 and 2 of P haemolytica contained a comigrating 30-kDa
      protein. Antibody responses to proteins of 39, 33, and 32.5 kDa were significant
      for 3 of the untypeable strains and had significant correlation to lesion scores.
      Antibody responses to various other proteins were significant for 2 untypeable
      strains each.

PMID- 1378251
TI  - Detection and antigenicity of chlamydial proteins that bind eukaryotic cell
      membrane proteins.
AB  - Chlamydia psittaci proteins capable of binding eukaryotic cell membranes were
      identified and antigenically characterized. Cell membrane proteins (CMP) of
      noninfected cells were labeled with biotin (B-CMP), then were extracted with 1%
      Triton X-100. Nitrocellulose membrane strips containing sodium dodecyl sulfate
      polyacrylamide gel electrophoresis-resolved proteins of chlamydial elementary
      bodies (EB) were reacted with the B-CMP extract, followed by addition of
      streptavidin-conjugated horse radish peroxidase. Among the various strains of
      chlamydiae examined, a protein of approximately 16 to 18 kDa consistently bound B
      CMP. A second larger protein, ranging in molecular mass from 24 to 32 kDa, also
      bound B-CMP. Immunoblotting techniques were used to analyze the reactions of
      antisera from immunized and experimentally infected animals to these proteins. A
      rabbit polyclonal antiserum produced against the 18-kDa adhesin of a serovar-1
      strain of C psittaci (B577) reacted strongly with 18-kDa proteins of all C
      psittaci strains, but weakly with that of C trachomatis. Mouse antisera raised
      against the serovar-2 (FC-Stra) 28-kDa protein reacted only with proteins of the
      homologous serovar. Sera from experimentally infected animals did not react with
      the C trachomatis 18-kDa adhesion protein, but did react in 2 patterns with
      related and nonrelated C psittaci isolates. Two rabbits inoculated with infective
      serovar-1 EB and 1 rabbit inoculated with a serovar-2 strain reacted specifically
      with the 18-kDa proteins of their homologous serovars. In contrast, 2 other
      rabbits inoculated with the same serovar-2 strain produced antisera that reacted
      with all C psittaci 18-kDa proteins, as did serum from a similarly inoculated
      bull.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378252
TI  - Role of potassium channels in bronchodilator responses in human airways.
AB  - The plasma membrane of airway smooth muscle contains a high density of K+
      channels of various types that mainly regulate membrane potential. To examine
      whether these K+ channels are involved in bronchodilating mechanisms in human
      airways, relaxation concentration-response studies to isoproterenol,
      theophylline, and a K(+)-channel opener, lemakalim (BRL 38227), were obtained in
      the presence or absence of charybdotoxin (ChTX) (10 or 100 nM), an inhibitor of
      large conductance Ca(2+)-activated K+ channels (KCa) in smooth muscle. The
      effects of other potassium channel blockers, apamin (0.1 microM, a small
      conductance KCa blocker) and BRL 31660 (10 microM, an ATP-sensitive K(+)-channel
      blocker) on isoproterenol-induced bronchodilation were also examined. All
      relaxation studies were performed on spontaneous tone and in the presence of 1
      microM indomethacin. ChTX produced a dose-dependent significant rightward shift
      in the isoproterenol relaxation response curves without changing maximum
      relaxation; geometric mean values of EC50 were 4.6 nM without and 19 nM with 10
      nM ChTX (n = 7, p less than 0.005), and 3.4 nM without and 41 nM with 100 nM ChTX
      (n = 4, p less than 0.05), respectively. The theophylline relaxation responses
      were inhibited to a lesser extent by ChTX (10 nM) (ED50 of 32 microM without and
      71 microM with ChTX, n = 7, p less than 0.05), whereas lemakalim-induced
      relaxation response was not affected. Other K(+)-channel blockers, apamin and
      BRL31660, failed to affect isoproterenol-induced bronchodilation. These results
      suggest that ChTX-sensitive K+ channels are involved in bronchodilation induced
      by beta-agonists and theophylline in human airways.

PMID- 1378253
TI  - Modulation of bronchial reactivity by angiotensin-converting enzyme in
      unanesthetized guinea pigs.
AB  - To investigate the role of angiotensin-converting enzyme (ACE) in the modulation
      of bronchial reactivity, we tested the effects of a specific ACE inhibitor,
      captopril (CAP), on the bronchial reactivity to substance P (SP) and methacholine
      (MCH) in unanesthetized guinea pigs. The relative role of ACE on the vascular
      endothelium and ACE in the airway tissue was examined by administering CAP as an
      intravenous infusion and by an inhaled aerosol. Bronchial reactivity was
      evaluated by a provocative dose of SP or MCH at a concentration that would double
      the baseline value of the specific airway resistance (PC200 or PD200). Neither
      pretreatment with infused CAP (10 mg/kg) nor inhaled CAP (5 mg) enhanced
      bronchial reactivity to inhaled SP, whereas the reactivity to infused SP (7.5 x
      10(-3) to 20 nM/kg) was enhanced significantly by pretreatment with infused CAP
      (10 mg/kg) (p less than 0.05). The infusion of CAP (10 mg/kg) also enhanced the
      bronchial reactivity to both infused MCH (0.05 to 25 micrograms/kg) and inhaled
      MCH (0.05 to 25 mg/ml) (both p less than 0.05). However, the inhalation of CAP (5
      mg) did not affect the bronchial reactivity to inhaled MCH. These observations
      suggest that ACE located on the vascular endothelium may modulate bronchial
      reactivity.

PMID- 1378254
TI  - Pretreatment with aerosolized capsaicin potentiates histamine-induced
      bronchoconstriction in guinea pigs.
AB  - The aim of the present study was to examine whether endogenous neuropeptides
      released from sensory nerves can potentiate airway responsiveness to histamine.
      Total pulmonary resistance (RL) was measured to assess the bronchial
      responsiveness to increasing doses of histamine (1.25, 2.5, 5, and 10
      micrograms/kg) administered intravenously in 29 anesthetized and artificially
      ventilated guinea pigs. Pretreatment with aerosolized capsaicin (3 micrograms/ml
      for 15 to 60 s) 30 min before obtaining the dose-response to histamine
      significantly potentiated percent increase in RL caused by each dose of
      intravenously administered histamine. Pretreatment with substance P (0.5 ml/kg of
      10(-5) M) administered intravenously also potentiated the airway responsiveness
      to histamine. As assessed by the amount of extravasation of Monastral blue
      pigments, both capsaicin aerosol and substance P injected intravenously induced
      increased vascular permeability in the tracheal mucosa. These findings suggest
      that endogenous neuropeptides, especially tachykinin such as substance P, can
      induce airway hyperresponsiveness to nonspecific stimuli and play a possible role
      in producing airway hyperresponsiveness in bronchial asthma.

PMID- 1378255
TI  - Screening of a Babesia bigemina cDNA library with monoclonal antibodies directed
      to surface antigens.
AB  - A Babesia bigemina cDNA library prepared in lambda ZAP bacteriophage vector was
      immunoscreened to detect clones expressing surface-exposed epitopes of B.
      bigemina. A nonradioactive indirect plaque-lift immunoassay was used to detect
      the positive clones. The primary antibody consisted of a pooled sample of six
      monoclonal antibodies (mAb) specific for B. bigemina that recognizes various
      parasite surface antigens of different molecular mass. Screening of approximately
      300,000 plaque-forming units from the lambda ZAP cDNA expression library resulted
      in the identification of five positive clones. The five recombinant clones were
      immunoscreened individually with each of the six mAb. All five independently
      obtained clones consisted of lambda ZAP recombinants expressing B. bigemina
      components recognized by mAb C2F3G3 and B1B3C4. Restriction enzyme digests of
      rescued recombinant phagemids showed that only four clones contained B. bigemina
      cDNA. One clone (lambda ZAP Bbi1) contained an insert of approximately 0.6 kBp
      whereas the other three clones (lambda ZAP Bbi2, lambda ZAP Bbi3, and lambda ZAP
      Bbi5) carried a cDNA insert of approximately 1.7 kBp. Immunoblotting of protein
      extracts from recombinants lambda ZAP Bbi2, lambda ZAP Bbi3, and lambda ZAP Bbi5
      with mAb C2F3G3 and B1B3C4 demonstrated the expression of a recombinant B.
      bigemina polypeptide of 55 kDa in E. coli.

PMID- 1378256
TI  - Tracheobronchial obstruction from esophageal carcinoma: bronchoscopic treatment
      with neodymium: yttrium-aluminum-garnet laser.
AB  - Tracheobronchial obstruction resulting from esophageal carcinoma is uncommon.
      Patients with advanced esophageal carcinoma with tracheobronchial obstruction
      usually present with severe dyspnea or hemoptysis or both and may die of
      suffocation. The Lahey Clinic experience using laser bronchoscopy for the
      palliation of symptoms of airway obstruction in patients with esophageal
      carcinoma is presented. From 1982 to 1990, nine patients were treated in 13
      procedures using the neodymium: yttrium-aluminum-garnet laser. Of the patients,
      seven had undergone previous treatment of the primary tumor. Tumors were located
      in the trachea in seven patients and in the main stem bronchi in three patients.
      Improvement of the airway caliber was achieved in all patients with relief of the
      dyspnea. The mean hospital stay was 2 days. One patient lived 4 years after laser
      treatment with no recurrence of tumor, and one patient died 1 week after
      treatment as a result of his poor general condition. The rest of the patients
      lived 3 to 41 weeks, with a median survival of 35 weeks. No complications were
      related to the procedures, and in particular, no tracheoesophageal fistulas
      developed. Our experience indicates that bronchoscopic application of this laser
      in conjunction with other treatment modalities can improve the quality and
      duration of life in selected patients with esophageal carcinoma that invades and
      obstructs the trachea.

PMID- 1378257
TI  - The value of acute phase protein measurements in clinical practice.
AB  - There is clearly a role for the measurement of acute phase proteins and other
      indices of the acute phase reaction but it is equally clear that no one
      laboratory test is suitable for use in all clinical situations. The choice of
      acute phase protein measurement depends on the diagnostic sensitivity and
      specificity of the measurement in the particular clinical situation. The choice
      of measurement must also include a decision on time of sampling and whether
      single or serial sampling would be more appropriate. In most situations where
      acute phase measurement is useful CRP is the assay of choice with alpha 1
      antichymotrypsin also being useful in inflammatory bowel disease and other
      situations where a wider time window is required. The ESR or plasma viscosity can
      be useful to screen for disease. Cytokine and enzyme-inhibitor complex
      measurements may be important assays in the future.

PMID- 1378258
TI  - Mononuclear cell subsets and coronary artery lesions in Kawasaki disease.
AB  - The peripheral blood mononuclear cell subsets in patients with Kawasaki disease
      and coronary artery lesions were investigated. Of the 106 patients 14 had
      lesions. Patients with Kawasaki disease and coronary artery lesions were found to
      have increased counts of CD14+ macrophages/monocytes compared with those of
      patients with Kawasaki disease without lesions. The absolute counts of CD14+
      macrophages/monocytes form an important parameter to determine the severity of
      vascular damage during acute Kawasaki disease.

PMID- 1378260
TI  - Assessing symptom improvement after elective prostatectomy for benign prostatic
      hypertrophy.
AB  - BACKGROUND: Elective surgery for benign prostatic hypertrophy requires estimates
      of likely improvement. METHODS: Data are from a prospective study of all patients
      without cancer who underwent transurethral prostatectomy. After eliminating
      patients for whom surgery was not elective, we examined symptom improvement.
      RESULTS: Surgery was effective in reducing symptoms for all but those with very
      mild preoperative symptoms. For the remainder, the average level of postoperative
      outcomes achieved was independent of the initial symptom severity. CONCLUSIONS:
      Elective prostatectomy is effectiveness for improving symptoms. The improvement
      is typically sustained, and for some symptoms improvement continues during the
      first year after surgery. Patients with severe symptoms were as likely to achieve
      the same level of postoperative improvement as were patients with less severe
      problems initially. However, patients with very mild symptoms benefited little or
      none from surgery.

PMID- 1378259
TI  - Dysmorphic features in offspring of alcoholic mothers.
AB  - The frequencies of 60 minor physical anomalies and various craniofacial
      measurements in 52 children with alcohol exposure of various durations in utero
      were determined and compared with 48 non-exposed healthy children at a mean age
      of 27 months. Compared with non-exposed children a significantly higher total
      minor physical anomaly count was observed in those children exposed prenatally to
      alcohol throughout pregnancy. Binge drinking was not associated with an increased
      minor physical anomaly count. During the first year of life facial features were
      judged according to subjective impression: 10 children had typical facial
      features of fetal alcohol syndrome (FAS) and 19 children were judged to have
      possible fetal alcohol effects on their face. Only six of them fulfilled the
      strict craniofacial criteria for diagnosis of FAS at the age of 27 months. Our
      results stress the importance of recognising also the subtle dysmorphic facial
      features associated with prenatal alcohol exposure: 22 of 29 (76%) of exposed
      children judged to have typical or possible features of FAS during the first year
      showed signs of central nervous system dysfunction at the age of 27 months.

PMID- 1378261
TI  - Brain monoamines and amino acids in Gilles de la Tourette's syndrome: a
      preliminary study of subcortical regions.

PMID- 1378262
TI  - Salmonella enteritidis-specific monoclonal antibodies.
AB  - Three monoclonal antibodies (MAbs) were derived that are specific for Salmonella
      enteritidis. Such antibodies are of interest because reagents that specifically
      identify S. enteritidis are potentially useful for the diagnosis and detection of
      this pathogen. Immunization of BALB/c mice with intact, unfixed, ultraviolet
      killed S. enteritidis permitted the derivation of a collection of hybridomas
      among which were found three MAbs: 1053, 1110, and 1170. Each MAb reacted with
      six independent field isolates of S. enteritidis, including phage type 4.
      However, none of these S. enteritidis-specific MAbs reacted with any of the
      following members of a broad diversity of Salmonella species: S. typhimurium, S.
      pullorum, S. berta, S. agona, S. dublin, S. miami, S. heidelberg, S. montevideo,
      S. senftenberg, and S. schwarzengrund. The S. enteritidis-specific determinant
      recognized by these MAbs is heat-labile, and preliminary experiments indicate
      that at least two of the MAbs recognize the same determinant.

PMID- 1378263
TI  - Cold exposure increases glucose utilization and glucose transporter expression in
      brown adipose tissue.
AB  - When rats were exposed to a cold environment (4 degrees C) for 10 days, tissue
      glucose utilization was increased in brown adipose tissue (BAT), a tissue
      specified for non-shivering thermogenesis, but not in skeletal muscle. Cold
      exposure also caused an increase in the amount of GLUT4, an isoform of glucose
      transporters expressed in insulin-sensitive tissues, in parallel with an
      increased cellular level of GLUT4 mRNA. In contrast to BAT, no significant effect
      of cold exposure was found in skeletal muscle. The results suggest the cold
      induced increase in glucose utilization by BAT is attributable, at least in part,
      to the increased expression of GLUT4.

PMID- 1378264
TI  - Structure-function relationship of basic fibroblast growth factor: site-directed
      mutagenesis of a putative heparin-binding and receptor-binding region.
AB  - Basic residues Arg-118, Lys-119, Lys-128, and Arg-129 within a putative heparin
      binding and receptor-binding region of the 155-amino acid form of basic
      fibroblast growth factor (bFGF) have been changed to neutral glutamine residues
      by site-directed mutagenesis of the human bFGF cDNA. The bFGF mutant (M6B-bFGF)
      was expressed in E. coli and purified to homogeneity. When compared to wild type
      bFGF, M6B-bFGF showed in cultured endothelial cells a similar receptor-binding
      capacity and mitogenic activity, but a reduced affinity for heparin-like low
      affinity binding sites, a reduced chemotactic activity, and a reduced capacity to
      induce the production of urokinase-type plasminogen activator. In vivo, M6B-bFGF
      lacked a significant angiogenic activity. Modifications of both the primary and
      the tertiary structure of bFGF appear to be responsible for the modified
      biological properties of M6B-bFGF, thus confirming the possibility to dissociate
      at the structural level some of the biological activities exerted by bFGF on
      endothelial cells.

PMID- 1378265
TI  - Identification of a set of genes with developmentally down-regulated expression
      in the mouse brain.
AB  - Using a subtraction cloning approach, we have isolated a set of cDNA clones from
      mouse neural precursor cells whose respective mRNA levels are down-regulated
      during the development of mouse brain. Single stranded DNA prepared from neuronal
      precursor cell cDNA library in lambda Zap vector was subtracted with poly (A)+
      RNA prepared from postnatal and adult mouse brain to obtain several clones which
      show developmental down-regulation of expression. Their patterns of expression
      indicate that these genes may play important roles during the embryonic
      development and differentiation of central nervous system.

PMID- 1378266
TI  - The protein kinase C inhibitor, calphostin C, inhibits succinate-dependent
      mitochondrial reduction of MTT by a mechanism that does not involve protein
      kinase C.
AB  - The light-activated protein kinase C inhibitor, calphostin C, is shown to inhibit
      the ability of IL-3-dependent 32D cells to reduce the tetrazolium salt, MTT. To
      determine whether this inhibition was mediated through mitochondria which have
      been implicated in MTT reduction, isolated mitochondria were treated with
      calphostin C in the presence of various substrates for mitochondrial electron
      transport and EDTA (to exclude PKC involvement). Calphostin C extensively
      inhibited succinate-dependent MTT reduction (IC50 = 110nM) but had little effect
      on either NADH- or NADPH-dependent MTT reduction. An alternative protein kinase C
      inhibitor, H7, did not affect succinate-dependent mitochondrial MTT reduction,
      and the protein kinase A inhibitor, KT5720, had little effect on either cellular
      or mitochondrial MTT reduction. These results show that in addition to its role
      as a PKC inhibitor, calphostin C is also a potent inhibitor of succinate
      dependent mitochondrial electron transport.

PMID- 1378268
TI  - The cDNA cloning, nucleotide sequence and expression of an intracellular protein
      tyrosine phosphatase from mouse testis.
AB  - The PTP-1 cDNA encoding an intracellular protein tyrosine phosphatase (PTPase)
      was isolated and sequenced from a mouse testis cDNA library. This PTP-1 cDNA was
      found to contain an open reading frame of 1,296 nucleotides as well as 5' (83
      nucleotides) and 3' (289 nucleotides) non-coding regions. The deduced sequence of
      432 amino acids of mouse PTPase-1 exhibited 93% and 83% identity to that of rat
      PTPase-1 and human PTPase-1B, respectively. Thus, this PTP-1 is a mouse homologue
      of human PTP-1B and rat PTP-1. Northern blot analysis indicated that PTP-1 mRNAs
      were most abundant in testis, and were detected in sizes of 4.4 Kb, 2.4 Kb and
      2.2 Kb, 2.0 Kb. The PTP-1 transcripts of 4.4 Kb and 2.0 Kb, but not 2.4 Kb and
      2.2 Kb, were also present in kidney, spleen, muscle, liver, heart and brain.
      Genomic blot analysis showed that a single copy of the PTP-1 gene is contained in
      the mouse genome and that introns are present in mammalian PTP-1 genes.

PMID- 1378267
TI  - Rat guanylin cDNA: characterization of the precursor of an endogenous activator
      of intestinal guanylate cyclase.
AB  - Guanylin is a recently discovered endogenous activator of intestinal guanylate
      cyclase that was purified from intestinal tissue. Clones have been isolated which
      demonstrate that the guanylin peptide is contained within a 115 amino acid
      apparent preprohormone encoded by a 600 base messenger RNA in rat jejunum. The
      messenger RNA is found predominantly in intestinal tissues, showing a striking
      gradient of expression ranging from undetectable in esophagus and stomach to
      abundant in colon. Guanylin may serve a paracrine function to regulate intestinal
      guanylate cyclase activity, cyclic GMP levels, and thereby, fluid and electrolyte
      absorption. We hypothesize that the heat stable enterotoxins mimic the
      endogenously produced guanylin to cause diarrhea.

PMID- 1378269
TI  - Enhancement of IL-6 receptor beta chain (gp130) expression by IL-6, IL-1 and TNF
      in human epithelial cells.
AB  - Analysis of the IL-6 Receptor beta chain (gp130) mRNA expression on the two human
      epithelial cell lines UAC and Hep3B reveals that it is enhanced by IL-6, IL-1 and
      TNF treatment. In the case of UAC cells, TNF action might be mediated by IL-6.
      For Hep3B cells, TNF seems to exert a direct effect on gp130, as no IL-6
      expression is detected after stimulation by this cytokine. On the same cells,
      increase of the binding of an anti-gp130 monoclonal antibody was observed after
      treatment by TNF, which denotes the effective appearance of new gp130 molecules
      on the cell surface. All this cytokines seem to act selectively on the beta chain
      of the IL-6 receptor. This probably reflects the importance for some cells to
      have gp130 represented on their membrane in inflammatory contexts.

PMID- 1378270
TI  - A common enzyme may be responsible for the conversion of organic nitrates to
      nitric oxide in vascular microsomes.
AB  - We compared the nitric oxide (NO)-generating behavior of nitroglycerin (NTG),
      pentaerythritol trinitrate (PEtriN) and isosorbide dinitrate (ISDN), in the
      microsomal preparation of bovine coronary artery smooth muscle cells. The
      comparative NO generating activities among these nitrates were consistent with
      their relative reported vasodilating activities. Consistent with our previous
      observations with NTG, 400 microM bromosulfophthalein did not affect NO
      generation from PEtriN and ISDN in vascular microsomes while 400 microM 1-chloro
      2,4-dinitrobenzene completely inhibited NO generation from these nitrates. Gel
      filtration chromatography with solubilized microsomes of bovine aortic smooth
      muscle cells showed the primary activity of NO generation from all three nitrates
      to be eluted at about 200 kD, consistent with that found with solubilized
      microsomes from the bovine coronary artery microsomes. These results suggest that
      organic nitrates may be converted to NO by one common enzyme in vascular
      microsomes.

PMID- 1378271
TI  - Prothymosin alpha expression occurs during G1 in proliferating B or T
      lymphocytes.
AB  - To gain insight into possible functions for prothymosin alpha in the
      proliferative cycle of lymphocytes, we examined the kinetics of prothymosin alpha
      mRNA expression in mitogen stimulated murine lymphocytes. This mRNA increases
      after mitogen stimulation, peaking in mid G1. This kinetics is compatible with
      induction of the prothymosin alpha gene by the c-myc protein (Eilers, M., Schirm,
      S. and Bishop, J.M. (1991) EMBO J., 10, 133-141). Thus, although prothymosin
      alpha mRNA is found throughout the cell cycle, the elevated expression in G1 may
      be associated with an increased requirement for prothymosin alpha during the G1/S
      transition or the S phase of the cell cycle.

PMID- 1378272
TI  - Nitric oxide synthase from cerebellum catalyzes the formation of equimolar
      quantities of nitric oxide and citrulline from L-arginine.
AB  - This study examined whether constitutive nitric oxide (NO) synthase from rat
      cerebellum catalyzes the formation of equimolar amounts of NO plus citrulline
      from L-arginine under various conditions. Citrulline was determined by monitoring
      the formation of 3H-citrulline from 3H-L-arginine. NO was determined by
      monitoring the formation of total NOx (NO+nitrite [NO2-] + nitrate [NO3-]) by
      chemiluminescence after reduction of NOx to NO by acidic vanadium (III). Equal
      quantities of NO plus citrulline were generated from L-arginine and the formation
      of both products was linear for about 20 min at 37 degrees C provided L-arginine
      was present in excess to maintain a zero order reaction rate. Deletion of NADPH,
      addition of the calmodulin antagonist calmidazolium, or addition of NO synthase
      inhibitors (NG-methyl-L-arginine, NG-amino-L-arginine) abolished or markedly
      inhibited the formation of both NO and citrulline. The Km for L-arginine (14
      microM; 18 microM) and the Vmax of the reaction (0.74 nmol/min/mg protein; 0.67
      nmol/min/mg protein) were the same whether NO or citrulline formation,
      respectively, was monitored. These observations indicate clearly that NO and
      citrulline are formed in equimolar quantities from L-arginine by the constitutive
      isoform of NO synthase from rat cerebellum.

PMID- 1378274
TI  - A selective and potent antagonist of substance P receptors on pancreatic acinar
      cells.
AB  - CP-96,345 [(2S, 3S) cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-
      azabicyclo[2.2.2]octan-3-amine] belongs to a new class of nonpeptide antagonists
      of the substance P (SP) receptor. The effects of this compound on [125I]-labelled
      Bolton-Hunter substance P ([125I]-BH-SP) binding and cytoplasmic Ca2+ ([Ca2+]i)
      responses of pancreatic acinar cells have now been studied. IC50 of CP 96,345 for
      binding of [125I]-BH-SP and for SP-induced (3 x 10(-9) M) rise of [Ca2+]i were
      about 10(-9) M. CP-96,345 neither affected binding of [125I]-labelled Bolton
      Hunter cholecystokinin octapeptide ([125I]-BH-CCK-8) nor the [Ca2+]i responses to
      CCK-8, carbamylcholine or bombesin. The CP-96,345-induced inhibition of [Ca2+]i
      responses to SP appeared reversible after withdrawal of the antagonist and was
      overcome by increasing the concentration of the agonist. CP-96,345 was
      consequently a specific and potent competitive antagonist for SP receptors on
      pancreatic acinar cells.

PMID- 1378273
TI  - Cloning of the rat insulin-like growth factor binding protein-1 gene and analysis
      of its 5' promoter region.
AB  - To understand specific mechanisms involved in the regulation of insulin-like
      growth factor binding protein-1 (IGFBP-1), an important modulator of IGF
      bioactivity, we cloned the rat IGFBP-1 gene and sequenced a 1.5 kb Sph1-Sph1
      fragment containing 1110 bases upstream from the translation start site. Computer
      analysis reveals the presence of ATA, CACCC, and CCAAT elements, and putative
      homeodomain, AP-1, insulin and glucocorticoid response elements in the 5'
      promoter. Primer extension and ribonuclease protection studies reveal a single
      cap site in RNA from rat hepatoma cells and both control and diabetic rat liver.

PMID- 1378275
TI  - "The effect of hCG-induced desensitization on RNA synthesis in rat Leydig cells".
AB  - In this study we have examined the effect of hCG-induced desensitization on RNA
      synthesis in rat Leydig cells. In vitro [3H]-uridine incorporation into RNA
      decreased after a high, single dose of hCG (100 IU). This effect was maximal
      after the second and third day of treatment. When Leydig cells were incubated in
      vitro for 30 min or more, a marked decrease of total and poly(A)+ RNA synthesis
      was observed. This was not due to reduced cell permeability to the radioactive
      nucleotide, indicating a truly decreased RNA synthesis during desensitization.
      The magnitude of this inhibitory effect (73-80%) suggests that desensitization
      may involve other biological functions of Leydig cell.

PMID- 1378276
TI  - Expression of low density lipoprotein receptor, apolipoprotein AI, AII and AIV in
      various rat organs utilizing an efficient and rapid method for RNA isolation.
AB  - Intact RNA from various rat organs was isolated by an efficient and rapid method.
      This method of RNA isolation is a modification of an earlier method that uses
      guanidinium isothiocynate followed by extraction in the presence of sarcosyl,
      acetate and phenol. The RNA obtained by the method reported here was comparable
      with the RNA prepared by the CsCl2 ultracentrifugation method and the
      commercially available kit based on published methods. The quality of RNA was
      found suitable for Northern blotting analysis, RNase protection assays and
      reverse transcriptase-polymerase chain reaction (RT-PCR). Since reverse
      transcriptase is active in the buffer used for Taq DNA polymerase, only one
      reaction needs to be set up. We also found that the use of aurintricarboxylic
      acid in the RNA preparation prevents the degradation of RNA during storage.
      Expression of low density lipoprotein (LDL) receptor, apolipoprotein (apo) AI,
      AII and AIV mRNAs were quantified in various rat organs. Our results indicated
      that rat LDL receptor mRNA is expressed in several organs whereas apoAI and AIV
      mRNAs were expressed mainly in the liver and intestine. However, apo AII mRNA is
      expressed mainly in the liver. Unlike mice and some species of monkeys, in the
      rat apoAI mRNA is expressed at 5-6 times higher levels in the intestine compared
      to liver. Apo AIV mRNA abundance was also found to be several fold higher in
      intestine compared to hepatic tissues. We present here, for the first time, data
      on the absolute amounts of LDL receptor, apoAI, AII and AIV mRNA in various rat
      organs which were quantified by a novel RNase protection/solution hybridization
      assay.

PMID- 1378277
TI  - Beta 2-adrenergic receptor antibodies in myasthenia gravis.
AB  - Although autoantibodies against the nicotinic acetylcholine receptor are the
      characteristic feature of the autoimmune disease myasthenia gravis (MG), no
      strong correlation is found between the autoantibody titer and the degree of
      clinical severity. Numerous studies have attempted to detect the presence of
      other autoantibody populations that might have a role in the pathology of the
      disease. We report, for the first time, that 18% of the MG patients we screened
      have antibodies in their serum to a peptide corresponding to the second
      extracellular loop of the human beta 2-adrenergic receptor (residues 172-197).
      Affinity purified antibodies to the beta 2-adrenergic receptor peptide 172-197
      reacted with the human beta 2-adrenergic receptor protein obtained from
      transfected E. coli cell membrane extracts, but did not cross-react with the
      human AChR. Sufficient material was obtained from nine MG patients and it was
      found that the gamma globulin fraction from these patients immunoprecipitated the
      receptor, and that affinity purified IgG to peptide 172-197 competed for receptor
      binding with the beta-antagonist iodo-cyanopindolol. Using truncated peptides or
      amino acid modification procedures, no immunodominant B-cell epitope could be
      detected within region 172-197. Thus, a subpopulation of MG patients possesses
      anti-beta 2-adrenergic receptor antibodies which are a distinct set of
      autoantibodies with possible pharmacological activity.

PMID- 1378278
TI  - Renal graft rejection or cyclosporin toxicity? Early diagnosis by a combination
      of Papanicolaou and immunocytochemical staining of urinary cytology specimens.
AB  - A method is described for distinguishing between graft rejection and cyclosporin
      nephrotoxicity in renal allograft recipients by analyzing fresh morning urine
      samples. The technique combines classic Papanicolaou with immunocytochemical
      staining and was performed in urine specimens from a series of 42 patients. Early
      stage cyclosporin toxicity was usually associated with increased numbers of
      proximal tubular cells only, whereas in rejection and late-stage toxicity there
      were increases in both tubular cells and in lymphocytes and monocytes (greater
      than 2000 cells/ml urine). Differentiation between these two clinical conditions
      was achieved by immunostaining, which revealed that increased numbers of CD25+
      and CD8+ cells, as well as an increase in the HLA-DR/Lu5 ratio, were typical of
      rejection. CD25 positivity proved to be the best indicator of rejection, with a
      sensitivity and specificity of more than 90%. A cytodiagnostic algorithm is
      presented that is based on cell numbers and types, including immunophenotypes.
      The proposed method has the advantage of being noninvasive and appears to
      represent a reliable and rapid adjunct for the monitoring of graft function,
      especially in high-risk patients on cyclosporin immunosuppression.

PMID- 1378279
TI  - HIV-induced cysteine deficiency and T-cell dysfunction--a rationale for treatment
      with N-acetylcysteine.
AB  - Markedly decreased plasma cystine and cysteine concentrations have been found in
      HIV-infected patients at all stages of the disease and in SIV-infected rhesus
      macaques. The elevated glutamate levels found in the same patients aggravate the
      cysteine deficiency by inhibiting the membrane transport activity for cystine.
      The intact immune system appears to require a delicate balance between pro
      oxidant and antioxidant conditions, maintained by a limited and well-regulated
      supply of cysteine. This balance is obviously disturbed in HIV infection and may
      contribute to the pathogenesis of AIDS.

PMID- 1378282
TI  - The different routes of calcium efflux from liver mitochondria.
AB  - Calcium efflux from liver mitochondria, induced by an uncoupler during incubation
      at 20 degrees C, is largely inhibited by the prior addition of ruthenium red or
      EGTA. The inhibition by EGTA (i.e. by chelation of Ca2+) is impaired by the
      presence of EDTA (i.e. by chelation of Mg2+), and it is completely abolished by
      addition of spermine. In contrast, the inhibition of calcium efflux at 20 degrees
      C by ruthenium red is unaffected by EGTA or spermine. This latter pathway of
      calcium efflux therefore represents the reversal of the calcium uniporter. During
      incubation at 30 degrees C, uncoupler-induced calcium efflux is incompletely
      inhibited by ruthenium red, and the residual calcium efflux occurs via membrane
      transition. The kinetics of this process as well as its exceptionally strong
      dependence on temperature constitute the main evidence for considering that
      membrane transition modifies the uniporter, and that the modified uniporter is
      responsible for the residual calcium efflux. It was shown that the route of
      ruthenium red-insensitive calcium efflux from energized mitochondria under
      standard conditions is the same, irrespective of whether the uniporter is running
      or is blocked by ruthenium red. The development of methods for the clear
      experimental separation of these different routes of calcium efflux under
      different conditions is still critically important.

PMID- 1378280
TI  - The evolution of mouse and human complement C3-binding proteins: divergence of
      form but conservation of function.
AB  - Despite the fact that the early components of the mouse and human complement
      cascades are very similar, there are marked differences between the two species
      in the structure of C3 receptors and the molecules that control homologous lysis.
      Here, Michael Holers, Taroh Kinoshita and Hector Molina compare and contrast the
      mouse and human RCA region products and conclude that the receptor and regulatory
      roles are conserved despite the structural variation.

PMID- 1378281
TI  - Diagnosis of metastatic thymoma using flow cytometry.
AB  - Thymomas are cytologically benign epithelial neoplasms of the thymus gland. They
      compose 10% of mediastinal tumors, and are most common in the anterosuperior
      compartment. Seven to 36% of thymomas are malignant, as determined by tissue
      invasion, yet they metastasize in less than 3% of cases. Distinguishing lymphoma
      from lymphocyte-predominant thymoma is imprecise due to their histologic
      similarities. We present a 45-year-old man with intracranial metastatic thymoma.
      The lesion was interpreted radiographically as meningioma, and as possible
      lymphoma by frozen section. Flow cytometry proved this neoplasma to be a
      metastatic thymoma. Sixteen monoclonal antibodies were used to immunophenotype
      the CD45+ component of this tumor. Coexpression of CD4 and CD8 along with CD1
      demonstrated lymphocytes of late cortical thymocyte origin; a second component
      was cytokeratin positive. This is the first reported case of extrathoracic
      metastases of thymoma diagnosed using flow cytometry. We propose this method as
      an invaluable technique to diagnose these histologically difficult neoplasms.

PMID- 1378283
TI  - Effect of colony-stimulating factors on number and function of circulating
      monocytes in normal dogs.
AB  - Recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF)
      and recombinant canine granulocyte colony-stimulating factor (rcG-CSF) were
      administered to normal dogs, and effect on monocyte number and function was
      evaluated. rhuGM-CSF, administered for 14 days, induced a 2.5-fold increase in
      monocyte counts on day 3. Leukocytes increased two-fold after 1 day. Counts
      peaked on day 11, then declined, approaching pretreatment counts by day 15. On
      day 7, in vivo monocyte cytostasis activity was significantly enhanced, and
      declined on day 14. rcG-CSF induced a 4.5-fold increase in monocyte counts on day
      3. Leukocyte counts increased three-fold after 1 day. Increased counts were
      maintained for 69 days, at which time treatment was discontinued. There was no
      effect of rcG-CSF on in vivo monocyte cytostasis activity on days 7 and 14.

PMID- 1378284
TI  - A model system for DNA removal from protein solutions.

PMID- 1378285
TI  - Compensatory angiogenesis during progressive right ventricular hypertrophy.
AB  - We investigated vascular adaptations occurring in progressive right ventricular
      hypertrophy (RVH) in adult mini pigs. Fourteen mini pigs had progressive RVH
      induced by implanting an inflatable cuff on the main pulmonary artery for 1-5
      months and were compared to a control group (N = 11). RVH animals were divided
      into two groups, a moderate RVH (MH) that had RV/BW ratio increases of 20%-70%
      above controls and a severe hypertrophy group (SH) that had RV/BW ratio increase
      of 70%-117%. We measured coronary blood flow reserve (CBFR) with radiolabelled
      microspheres at maximal exercise and during adenosine vasodilation. Adenosine
      vasodilation did not decrease CBFR either regionally or transmurally in both the
      MH and SH groups. During exercise CBFR showed a small but significant decrease in
      the SH group. No intervention changed the endo/epi flow ratios. Morphometric
      studies showed that myocytes increased in cross sectional areas (CSA) in these
      hypertrophied hearts. The CSA of capillaries and arterioles and their numerical
      densities increased significantly in the endocardial and epicardial regions in
      both MH and SH groups. Capillary density showed a small but significant decrease
      in both MH and SH groups. We measured DNA synthesis in these hearts using
      tritiated thymidine labelling. We found a high labelling index in endothelial
      cells and a moderate labelling index in smooth muscle cells in early stages of
      hypertrophy. These data show that angiogenesis, observed in the morphometric
      studies and by DNA labelling, prevents CBFR changes during progressive RVH in the
      pig. Furthermore, angiogenesis is not uniform at different stages of progressive
      RVH.

PMID- 1378286
TI  - Expression of "cell-type-specific" markers during rat tracheal epithelial
      regeneration.
AB  - Previous studies showed that Griffonia simplicifolia I-isolectin B4 (GS I-B4) and
      monoclonal antibodies (mAbs) against keratin 14 labeled basal cells in the adult
      rat trachea while other mAbs specifically stained secretory and/or ciliated
      cells. We used these "cell-type-specific" markers to study cellular
      differentiation during tracheal epithelial regeneration. Denuded tracheal grafts
      were inoculated with rat tracheal epithelial cells and were implanted in
      syngeneic hosts. Marker expression was correlated with the appearance of
      morphologically defined cell types. At 4 days, the epithelium was squamoid, one
      to three cell layers thick, and was apparently composed of a single morphologic
      cell type. Because this cell did not exhibit distinguishing features of any
      mature tracheal cell, we provisionally termed it the "poorly differentiated cell"
      (PD cell). PD cells expressed keratin 14 and GS I-B4 binding sites; they
      contained glycogen and had lipid droplets but did not react with secretory or
      ciliated cell-specific mAbs. At 7 days, areas of the epithelium were
      pseudostratified and secretory cell-specific markers were present at the apex of
      differentiating columnar cells; ultrastructurally, these cells resembled
      secretory cells in adult tracheas. Simultaneously, a few preciliated and ciliated
      cells appeared that expressed a ciliated cell-specific epitope. No cells were
      observed coexpressing secretory and ciliated cell markers. Basal cells also
      became recognizable on day 7. These expressed keratin 14 and GS I-B4 binding
      sites throughout the study. Newly appearing secretory and ciliated cells also
      expressed these two markers initially but lost them gradually as the mucociliary
      epithelium matured. In the tracheal graft model of epithelial regeneration, the
      PD cells were pivotal intermediates from which all differentiated cells
      developed. Basal cells continued to express the same markers as PD cells, which
      were gradually lost in secretory and ciliated cells as they acquired new sets of
      specific epitopes.

PMID- 1378287
TI  - Endotoxin enhancement of lymphocyte adherence to cultured sheep lung
      microvascular endothelial cells.
AB  - The most common predisposing factor for development of the adult respiratory
      distress syndrome is gram-negative sepsis. Our previous studies have shown that a
      single infusion of Escherichia coli endotoxin into sheep causes early
      sequestration of lymphocytes in the lungs' microcirculation. In this report, we
      examined the effects of endotoxin on sheep lymphocyte adherence to sheep
      pulmonary microvascular endothelial cells in vitro. Endothelial cells were
      exposed to endotoxin, and subsequent adherence of 51Cr-labeled lymphocytes was
      measured in a monolayer adhesion assay. Endotoxin enhanced adherence of
      lymphocytes isolated from blood and caudal mediastinal node (CMN) lymph in a time
      and dose-dependent manner. Adherence of CMN lymphocytes increased from a control
      value of 13.6 +/- 1.6% to 29.9 +/- 3.1% after 4 h of treatment with 1
      microgram/ml endotoxin. Both B and T lymphocytes contributed to the increased
      adherence. Pretreatment of the endothelial cells with cycloheximide revealed that
      the endotoxin-enhanced adherence was partially dependent upon protein synthesis.
      Morphologic studies revealed that enhanced adherence was accompanied by a 5-fold
      increase in migration of lymphocytes between endothelial cells. In contrast to
      human umbilical vein endothelial cells, antibodies to the known lymphocyte
      adherence molecules, lymphocyte function-associated antigen (LFA-1), CD-44, and
      the lymphocyte homing receptor (LECAM-1), were ineffective in blocking adherence
      to the sheep pulmonary endothelial cells. We conclude that the acute
      sequestration of lymphocytes in the pulmonary microcirculation of sheep after
      endotoxin administration is due to increased adhesive properties of the
      endothelial cells. Our data suggest that this adherence is mediated by as yet
      undescribed mechanisms that may be unique to pulmonary microvascular endothelium.

PMID- 1378288
TI  - Lung capillary endothelial cells produce and secrete urokinase-type plasminogen
      activator.
AB  - Bovine lung capillary endothelial cells (BLuEC) were isolated, and their ability
      to produce plasminogen activator (PA) in vitro was demonstrated. BLuEC secreted
      more than 10 times as much as urokinase-type PA (u-PA) as did bovine aortic,
      hepatic capillary and adrenal capillary endothelial cells, and lung fibroblasts.
      BLuEC secreted u-PA on both sides of the cell layer, the luminal surface, and the
      basic surface attached to the basement membrane. u-PA mRNA was detected in BLuEC
      by Northern blotting, but not in endothelial cells from other tissues and
      fibroblasts. These results suggest that BLuEC may contribute not only to the
      patency of lung vessels but also to the maintenance of alveolar functions through
      the production and secretion of u-PA.

PMID- 1378289
TI  - Teniposide as single drug therapy for elderly patients affected by small cell
      lung cancer.
AB  - From January 1987 to December 1990, 26/105 previously untreated patients affected
      by small cell lung cancer (SCLC), not suitable for intensive SCLC treatment since
      19 of them were older than 70 years and 7 suffered from severe chronic diseases,
      received induction therapy consisting of teniposide alone, 60 mg/m2 on days 1-5,
      every 3 weeks until disease progression. After a minimum of two courses, 24
      patients were evaluable for response: 13 with limited disease (LD) and 11 with
      extensive disease (ED) (2 patients were unevaluable: 1 early death and 1 protocol
      violation). Response rate, by disease stage, was: in the 13 LD, 1 complete
      response (CR), 8 partial responses (PR), 2 minor responses and 2 failures; in the
      11 ED, 1 CR, 4 PR and 6 failures. The overall response rate was 58% (14/24) (95%
      confidence limits = 38-78%), comprising 8% CR and 50% PR. Median duration of
      response was 7 months (range 2-32). Median overall duration of survival was 9
      months (range 1.5-36+). Toxicity was haematological WHO grade III in 13% of
      courses delivered, whereas no further important side-effects were recorded,
      excluding alopecia, which was common. Teniposide used alone appeared a safe and
      effective palliative treatment for poor-risk patients; the major limitation was
      the low CR rate.

PMID- 1378290
TI  - Characterisation of insulin-like growth factor I receptors of human acute
      lymphoblastic leukaemia (ALL) cell lines and primary ALL cells.
AB  - The expression of insulin-like growth factor I (IGF-I) receptors (IGR-IR) on
      human B-lineage and T-lineage acute lymphoblastic leukaemias (ALL) representing
      different maturational stages has been studied. Immature (stage I) and mature
      (stage II) T ALL as well as pre-B ALL cell lines expressed high numbers of IGF-IR
      with high affinity for IGF-I. In contrast, on T ALL, stage II and B ALL only low
      specific binding of 125I-IGF-I was detected. No binding of 125I-IGF-I to Burkitt
      lymphoma cells was found. Primary human T, pre-B and cALL cells also expressed
      IGF-IR with Kd for IGF-I and IGF-IR number per cell in the same range as the
      investigated cell lines. Crosslinking of 125I-IGF-I to T and pre-B ALL cells
      revealed IGF-IR alpha-subunits of 135 and 116 kD for HSB2. Gene expression of IGF
      IR could be detected in all T ALL cell lines but was undetectable in SKW6, a B
      ALL cell line.

PMID- 1378291
TI  - Induction of MHC antigens by tumour cell lines in response to interferons.
AB  - The induction of major histocompatibility complex antigens by interferons (IFN)
      on 17 established tumour cell lines was investigated by radio binding. One
      bladder (Fen) and two testis lines (Tera I and Ha) lacked class I antigens and
      IFN-gamma failed to induce their expression. However, IFN-gamma upregulated these
      antigens on lines expressing low class I antigens (Tera II and EP2102) with
      little or no significant effect on high class I expressing lines (T24 and RT112).
      In one bladder line (Wil) IFN-gamma, whilst failing to alter monomorphic class I,
      upregulated polymorphic HLA-A2 and A3 antigens. None of the 17 lines expressed
      class II antigens, but could all be induced by IFN-gamma except T24, TccSup, Tera
      II and Lan lines. This defect was not due to the absence of IFN-gamma receptor,
      since under the same conditions intracellular adhesion molecule 1 was
      upregulated. IFN-alpha, whilst failing to have any effect on class II, induced
      class I antigens. IFN-beta showed no activity on either class I or II antigens
      when used alone. However, in combination, it inhibited IFN-gamma induced class II
      antigens. Thus, it may be possible to study cells from fresh tumours to preselect
      the minority of patients who might benefit from cytokine therapy.

PMID- 1378292
TI  - Polymeric Ig receptor expression in hepatocellular carcinoma.
AB  - The cellular localisation of the polymeric Ig receptor (pIg-R) and
      carcinoembryonic antigen (CEA), hepatic and biliary cell markers, were
      investigated in patients with hepatocellular carcinoma (HCC) and high serum
      levels of secretory component. Serum SC were increased 6-20-fold in 8 HCC
      patients compared with normal subjects. Serum free SC was positively correlated
      bilirubin (r = 0.95, P less than 0.04). In normal liver tissue, cytokeratin (CK)
      8 and 18 were localised in hepatocytes and biliary cells while pIg-R and CK 19
      expression was restricted to biliary cells. In tumoral liver tissue, malignant
      cells expressed CK 8 and 18 weakly; pIg-R and CK 19 were not detected in tumoral
      cells. CEA was expressed by biliary cells in normal and proliferating ducts. In
      peritumoral fibrosis, proliferating biliary cells were strongly stained by anti
      cytokeratins and anti-pIg-R antibodies. In one case, pIg-R was localised in
      isolated cells close to fibrosis without co-staining of anti-CK 19. Thus
      increased serum SC is not associated with pIg-R expression by tumoral cells, and
      pIg-R may be considered an additional marker of biliary cells. High SC might be
      explained either by reflux from bile to serum and/or release of unbound SC from
      the vascular pole of non-functional, proliferating biliary structures.

PMID- 1378293
TI  - Establishment and characterisation of a human glioma cell line.
AB  - A new cell line, CB109, has been established from a human glioblastoma
      multiforme. The cytoskeleton was positive for glial fibrillary acidic protein,
      vimentin and fibronectin. Hyaluronan (HA) and the HA-binding protein
      hyaluronectin (HN) were expressed in the cell cytoplasm and in the extracellular
      matrix of spheroids and plated cells. Hyaluronidase did not prevent spheroid
      formation suggesting that HA was not involved in the cell-cell adhesion. HA
      precoating prevented cell adherence to the plates and favoured spheroid
      formation. HA was secreted in relatively large amounts into the culture medium.
      High performance liquid chromatography demonstrated that HA was in the high
      molecular weight form. The rate of HN secretion by cells was very low. Basic
      fibroblast growth factor significantly increased the proliferation in vitro and
      tumour growth after grafting into nude mice. The epidermal growth factor receptor
      was not expressed on cultivated CB109 cells. Cytogenetic analysis showed polysomy
      7, structural rearrangement of chromosome 10 short arm and a translocation 13q13
      q14 without detectable alteration of the RB gene.

PMID- 1378295
TI  - C/EBP and c-JUN proteins activate the proximal enhancer of the developmentally
      regulated alpha-fetoprotein gene.
AB  - The expression of the alpha-fetoprotein (AFP) gene is developmentally regulated.
      Active transcription of this gene depends on a proximal enhancer sequence located
      between positions D-203 bp and -81 bp, upstream the initiation site. This
      enhancer contains several putative binding sites for transcription factors. By
      transfection experiments, we showed that the enhancer activity can be driven by
      interactions with two regulatory factors, namely C/EBP and c-JUN.

PMID- 1378296
TI  - Control of microtubule nucleating activity in the cytoplasm of maturing mouse
      oocytes.
AB  - Taxol, a drug which promotes microtubule assembly, was used to assess the
      microtubule nucleating activity of pericentriolar material (PCM) in mouse oocytes
      prevented from undergoing germinal vesicle breakdown (GVBD), compared with
      oocytes allowed to proceed normally through GVBD and also in nucleate and
      anucleate oocyte fragments. Both immunofluorescence staining and ultrastructural
      analysis reveal that taxol induces aster formation in the cortex of oocytes
      undergoing GVBD, while formation of a continuous sheet of microtubule bundles
      parallel to the membrane is induced in metabolically GV-arrested oocytes. Since
      taxol also induces the formation of asters in anucleate as well as in nucleate
      oocyte fragments, provided they are not treated with activators of protein
      kinases A or C, it is concluded that microtubule nucleating activity is related
      to the acquisition of Maturation Promoting Factor (MPF) and does not require
      mixing between the nucleoplasm and cytoplasm.

PMID- 1378297
TI  - Effects of cognate peptides on cytolytic and proliferative activities of cloned
      cytotoxic T lymphocytes.
AB  - When a cognate peptide is added to a culture of the corresponding clone of CD8+
      cytotoxic T lymphocytes (CTLs) having the appropriate major histocompatibility
      complex (MHC) each cell can serve as both an antigen-presenting target cell and
      as a responding CTL. Under these circumstances many of the cells die. The extent
      of cell death is greatly diminished by Ca2+ chelation (by Mg2 EGTA) and by mAbs
      to CD8 and to LFA-1. Cell death is also blocked by cyclosporin A and FK-506, but
      not by inhibitors of protein synthesis and gene transcription (cyclohexamide and
      actinomycin D respectively). In contrast to the stimulatory effect on cytolytic
      activity, proliferation of recently stimulated CTLs is profoundly inhibited by
      the cognate peptide, as well as by conventional target cells that are
      specifically recognized and lysed by the CTLs. The inhibition of proliferation is
      transient and is followed by enhanced DNA synthesis of surviving CTLs. Cognate
      peptides also elicit fragmentation of CTL DNA, and this effect is likewise
      decreased by cyclosporin A and FK-506. Thus the addition of a target, either in
      the form of a synthetic cognate peptide that associates with MHC proteins on
      intact CTLs or other cells, or in the form of a conventional target cell, can
      simultaneously stimulate cytolytic activity and inhibit the proliferative
      activity of mature CTLs.

PMID- 1378294
TI  - Influence of cyclic AMP and serum factors upon expression of a retinoid
      responsive gene in neuroblastoma cells.
AB  - Cyclic AMP can profoundly influence the growth and differentiation of neuronal
      cells in culture. In this study, the relationship between this second messenger
      signal transduction pathway, cell differentiation, and the expression of a
      retinoid-responsive, thymosin beta-10 gene was examined. Thymosin beta-10 and
      cognate mRNA were expressed at high levels in actively proliferating rat B104
      neuroblastoma cells cultured in medium containing 10% FCS. These cells were
      induced to differentiate in the presence of the cAMP analog N6, 2'-O
      dibutyryladenosine 3':5'-cyclic monophosphate (Bt2-cAMP) (1 mM) and the
      phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) (100 microM).
      Expression of thymosin beta-10 mRNA was markedly inhibited (greater than 90% and
      70%, respectively) by these compounds. Addition of sodium butyrate (NaB, 1 mM)
      indicated that at least part of the inhibitory actions of Bt2-cAMP were due to
      esterase-induced release of butyrate from this compound. Adenosine (50 microM), a
      metabolic precursor to endogenous cyclic AMP, also inhibited accumulation of
      thymosin beta-10 mRNA (to less than 70% of control levels). The inhibitory action
      of Bt2-cAMP upon thymosin beta-10 mRNA levels was time dependent; levels were
      inhibited by greater than 50% 24 hours after addition of the cAMP analog and by
      greater than 90% after 72 hours. Serum starvation (0.2% FCS for seven days)
      provoked a marked increase in neurite out-growth; this morphological change was
      also accompanied by a modest inhibition of thymosin beta-10 mRNA accumulation.
      These findings together with previous observations imply that both cyclic AMP
      dependent and retinoid-responsive mechanisms coordinate thymosin beta-10 gene
      expression during neuroembryogenesis.

PMID- 1378298
TI  - Evidence of endogenous regulatory function of transforming growth factor-beta 1
      in experimental allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune disease
      characterized by inflammation and demyelination in the central nervous system
      (CNS). Administration of transforming growth factor-beta (TGF-beta) has been
      shown to inhibit EAE. In this study, the possible role of endogenous TGF-beta in
      the regulation of relapsing EAE produced by the transfer of myelin basic protein
      specific T cell lines was assessed. Although TGF-beta is not present in the
      normal CNS, this cytokine was detected by immunohistology in areas of central
      nervous system inflammation in both acute and chronic disease. The administration
      of anti-TGF-beta at the disease onset led to a worsening of the clinical course
      of EAE and more extensive pathological lesions. These findings provide direct
      evidence for a role of endogenous TGF-beta in the remissions seen in chronic
      relapsing EAE.

PMID- 1378299
TI  - Cloning and characterization of the casein kinase II alpha subunit gene from the
      lymphocyte-transforming intracellular protozoan parasite Theileria parva.
AB  - Theileria parva is an obligate intracellular protozoan parasite which is the
      causative agent of East Coast fever, an acute, leukemia-like disease of cattle.
      The intralymphocytic stage of the parasite induces blastogenesis and clonal
      expansion of quiescent bovid lymphocytes. Experiments in our laboratory have
      shown a marked increase of casein kinase II- (CK II-) like activity in T. parva
      transformed lymphocytes. We have also detected CK II activity in purified T.
      parva schizonts. To explore the significance of this increase, we used a
      Drosophila melanogaster CK II alpha cDNA probe [Saxena et al. (1987) Mol. Cell
      Biol. 7, 3409-3417] to isolate a T. parva genomic clone encoding a CK II
      catalytic subunit. The clone contains a 1.3-kb open reading frame coding for a
      predicted protein of 420 amino acids (M(r) 50,200). Northern blot analysis
      revealed a single transcript of 1.65 kb. The deduced T. parva CK II catalytic
      subunit sequence shows, over 321 residues comprising the C-terminus of the
      molecule, extensive identity with CK II alpha and alpha' sequences from both
      vertebrate and invertebrate organisms. The T. parva CK II subunit amino acid
      sequence displays 68% identity with the Drosophila alpha subunit and 67% with the
      Caenorhabditis elegans alpha subunit but only 58% and 56% sequence identity with
      the Saccharomyces cerevisiae alpha and alpha' subunits, respectively. Comparison
      of the T. parva sequence with higher eukaryotic alpha and alpha' sequences
      reveals that it is most identical with the alpha subunit. A unique component of
      the T. parva CK II alpha subunit is a 99 amino acid sequence at the N-terminus,
      which contains a sequence motif with features characteristic of signal peptides.

PMID- 1378300
TI  - Sequence of a cDNA clone encoding the zinc metalloproteinase hemorrhagic toxin e
      from Crotalus atrox: evidence for signal, zymogen, and disintegrin-like
      structures.
AB  - The sequence of two overlapping cDNA clones for the zinc metalloproteinase
      hemorrhagic toxin e (also known as atrolysin e, EC 3.4.24.44) from the venom
      gland of Crotalus atrox, the Western diamondback rattlesnake, is presented. The
      assembled cDNA sequence is 1975 nucleotides in length and encodes an open reading
      frame of 478 amino acids. The mature hemorrhagic toxin e protein as isolated from
      the crude venom has a molecular weight of approximately 24,000 and thus
      represents the processed product of this open reading frame. From the deduced
      amino acid sequence, it can be hypothesized that the enzyme is translated with a
      signal sequence of 18 amino acids, an amino-terminal propeptide of 169 amino
      acids, a central hemorrhagic proteinase domain of 202 amino acids, and a carboxy
      terminal sequence of 89 amino acids. The propeptide has a short region similar to
      the region involved in the activation of matrix metalloproteinase zymogens. The
      proteinase domain is similar to other snake venom metalloproteinases, with over
      57% identity to the low molecular weight proteinases HR2a and H2-proteinase from
      the Habu snake Trimeresurus flavoviridis. The carboxy-terminal region, which is
      not observed in the mature protein, strongly resembles the protein sequence
      immediately following the proteinase domain of HR1B (a high molecular weight
      hemorrhagic proteinase from the venom of T. flavoviridis) and the members of a
      different family of snake venom polypeptides known for their platelet aggregation
      inhibitory activity, the disintegrins. The cDNA sequence bears striking
      similarity to a previously reported sequence for a disintegrin cDNA. This report
      is evidence that this subfamily of venom metalloproteinases is synthesized in a
      proenzyme form which must be proteolytically activated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1378301
TI  - Parameters that influence processive synthesis and site-specific termination by
      human immunodeficiency virus reverse transcriptase on RNA and DNA templates.
AB  - We have examined the parameters that determine the length and distribution of
      products synthesized processively by the human immunodeficiency virus reverse
      transcriptase (HIV-RT). On native or homopolymer templates, the overall length
      distribution of processively synthesized products is increased by increased
      temperature or deoxynucleoside triphosphate concentration, or decreased ionic
      strength. Specific terminations of processive synthesis on either native DNA or
      RNA templates occur most frequently at positions where the reverse transcriptase
      (RT) pauses during synthesis. These sites correlate with the template sequence 3'
      (A/U)(A/U)(G/C)-5', particularly when this sequence is predicted to be base
      paired with another region of the template in a secondary structure. Many
      positions of termination are in similar positions on DNA or RNA templates.
      Notable exceptions are runs of A residues, which promote termination on DNA but
      not RNA templates. Termination intensities vary when different RTs are used
      demonstrating an influence of RT structure.

PMID- 1378302
TI  - PCR detection of the rat brain basic fibroblast growth factor (bFGF) mRNA
      containing a unique 3' untranslated region.
AB  - We utilized the reverse transcription-polymerase chain reaction (RT-PCR) to
      detect the presence of basic fibroblast growth factor (bFGF) messenger RNA in rat
      brain, ovary and kidney. The nucleotide sequence of the RT-PCR product revealed a
      novel 3' untranslated (UT) sequence in the rat basic FGF mRNA. In this sequence,
      as in the 3' UT regions of many growth regulatory genes, there is a high degree
      of conservation of A+T rich motifs which have been shown to play a major role in
      mRNA stability.

PMID- 1378303
TI  - Sequence and expression of a rat cDNA for LECAM-1.
AB  - A rat cDNA clone encoding an adhesion molecule, LECAM-1, has been isolated from
      the SD rat and the partial nucleotide sequence was determined. It encodes a
      peptide of 372 amino acids (aa), including a signal peptide of 38 aa. The protein
      has three tandem domains: a lectin domain, an EGF-like domain and two repeats of
      complement regulatory proteins (CR domain). The lectin binding domain has 93.2%
      and 81.4% and the EGF-like domain has 85.3% and 76.5% aa identity with those of
      mouse and human, respectively. In the CR repeat domain, the amino acid identity
      was 72.6% between human and rat and 71.8% between mouse and rat. Northern blot
      analysis detects the main transcript of about 3 kb in peripheral blood
      mononuclear cells (PBMC), spleen and thymus. The expression was down-regulated by
      mitogen stimulation of PBMC and spleen T cells. The protein encoded by this cDNA
      interacted with PPME when it was expressed on gp90MEL-14 negative mouse EL-4
      cells.

PMID- 1378305
TI  - Effects of neonatal exposure to diethylstilbestrol on protein expression by
      vagina and uterus in mice.
AB  - Neonatal treatment of female mice with diethylstilbestrol (DES) results in
      genital tract abnormalities including ovary-independent vaginal proliferation and
      cornification. Protein profiles were examined in vagina and uterus from 45-day
      old, ovariectomized C57BL/Tw mice which had been given 5 daily injections of 2
      micrograms DES or oil vehicle alone from the day of birth, and in those from 45
      day-old, ovariectomized mice given 3 daily injections of 0.1 microgram DES from
      42 days of age. Proteins extracted were analyzed by two-dimensional
      polyacrylamide gel electrophoresis. In the vagina, expression of 37 non-keratin
      proteins was altered by postpubertal injections of DES as compared with the
      controls. In the neonatally DES-exposed vagina, expression of 26 of 37 proteins
      was altered as compared with controls. In the uterus, expression of 22 proteins
      was altered in the postpubertally DES-exposed group as compared with that in the
      control; however, the protein expression pattern of the neonatally DES-exposed
      group closely resembled that of the control except for one protein (no. 23, pI =
      6.1, MW = 39.5 kDa) which was specifically increased in the neonatally DES
      exposed group. By immunoblot analysis, 6 keratin polypeptides (49.5, 50, 52, 53,
      57 and 58 kDa) were identified in vaginae of ovariectomized mice exposed
      neonatally and postpubertally to DES and of the controls. These results indicate
      that neonatal DES exposure induces organ specific alterations in the synthesis of
      proteins in mouse vagina and uterus.

PMID- 1378304
TI  - Absence of tRNA-guanine transglycosylase in a human colon adenocarcinoma cell
      line.
AB  - Queuosine (Q), found exclusively in the first position of the anticodons of
      tRNA(Asp), tRNA(Asn), tRNA(His) and tRNA(Tyr), is synthesized in eucaryotes by a
      base-for-base exchange of queuine, the base of Q, for guanine at tRNA position
      34. This reaction is catalyzed by the enzyme tRNA-guanine transglycosylase (EC
      2.4.2.29). We measured the specific release of queuine from Q-5'-phosphate
      (queuine salvage) and the extent of tRNA Q modification in 6 human tumors carried
      as xenografts in immune-deprived mice. Q-deficient tRNA was found in 3 of the
      tumors but it did not correlate with diminished queuine salvage. The low tRNA Q
      content of one tumor, the HxGC3 colon adenocarcinoma, prompted us to examine a
      HxGC3-derived cell line, GC3/M. GC3/M completely lacks Q in its tRNA and
      measurable tRNA-guanine transglycosylase activity; the first example of a higher
      eucaryotic cell which lacks this enzyme. Exposure of GC3/M cells to 5-azacytidine
      induces the transient appearance of Q-positive tRNA. This result suggests that at
      least one allele of the transglycosylase gene in GC3/M cells may have been
      inactivated by DNA methylation. In clinical samples, we found Q-deficient tRNA in
      10 of 46 solid tumors, including 2 of 13 colonic carcinomas.

PMID- 1378306
TI  - Jack fruit lectin binding pattern in the exfoliative cytology of bronchopulmonary
      neoplasia.
AB  - N-acetyl D- galactosamine specific jack fruit lectin conjugate was used for the
      cyto-chemical study of benign and neoplastic lesions of the respiratory tract
      using diaminobenzidine as substrate on exfoliated cells and tissue sections.
      Sputum samples from patients with benign respiratory tract lesions (40), squamous
      cell Carcinoma (20), adenocarcinoma (16), small cell anaplastic carcinoma (12)
      and large cell anaplastic carcinoma (5) were used for the study. The lectin
      binding was strong in squamous cell carcinoma, large cell anaplastic carcinoma
      and adenocarcinoma, but variations in the binding pattern were observed in
      different carcinoma. Squamous metaplastic cells manifested slightly increased
      binding to lectin as compared to bronchial and native squamous epithelial cells.
      The nature of binding was eventually similar in cytology and histology. The ready
      availability and ease of preparation in purified from makes the jack fruit lectin
      a potential cytochemical reagent for sputum cytology.

PMID- 1378307
TI  - Synchronization, banding and in situ hybridization. A short laboratory manual.
AB  - A variety of culture, synchronization, banding and in situ hybridization
      techniques have been published in connection with chromosome studies. The present
      manual summarizes and discusses the most widely used techniques with special
      emphasis on the methods published by Ronne and coworkers from 1984-1991.

PMID- 1378308
TI  - Serum aluminum levels as a reflection of renal osteodystrophy status and bone
      surface aluminum staining.
AB  - Twenty eight (14%) out of 196 patients in a regional dialysis population were
      found to have serum aluminum levels greater than or equal to 5 mumol/L or 135
      micrograms/L; 21 consented to undergo a bone biopsy to identify the spectrum of
      renal osteodystrophy associated with this degree of hyperaluminemia. Both the
      Aluminon reagent and the acid solochrome azurine (ASA) stain were used to
      identify aluminum deposits. A control group of 13 patients with biochemical and
      histological evidence of severe secondary hyperparathyroidism was used to
      contrast the measured parameters of bone histology in the hyperaluminemic group.
      Al(OH)3 was used as the principal phosphate binder in all patients. In the
      hyperaluminemic group, 67% had either dialysis osteomalacia or aplastic bone
      lesions, and all except one aplastic lesion were positive for bone surface
      aluminum deposits by the Aluminon stain. The Aluminon stain was also positive in
      one of three cases of osteitis fibrosa and three of four mild lesions, whereas it
      was negative in all biopsies from the control group. However, the ASA stain was
      positive in all biopsies from the hyperaluminemic group and in 11 of 13 control
      biopsies from the patients with "pure" osteitis fibrosa. For all biopsy data from
      both groups, there were significant (P less than 0.01) negative correlations
      between the ASA-stained surface aluminum deposits and resorption indices (total
      eroded surface, r = -0.68; surface osteoclast counts, r = -0.53) and indices of
      bone formation (surface osteoblast counts, r = -0.61; mineral apposition rate, r
      = -0.63; bone formation rate, r = -0.69). These correlations were not significant
      for Aluminon-stained surface deposits with the exception of the bone formation
      indices, which had lower correlation coefficients (r = -0.44). These data suggest
      that hyperaluminemia greater than or equal to 5 mumol/L has a predictive value to
      identify impaired mineralization in dialysis patients that is high enough to
      affect clinical decision making. However, the more sensitive ASA stain identifies
      surface aluminum across the whole spectrum of renal osteodystrophy and is
      consistent with a toxic role for aluminum at any level of exposure.

PMID- 1378309
TI  - Capillary growth: a two-cell system.
AB  - Angiogenesis is central to a number of normal and pathologic processes, including
      tumor growth. The identification of several angiogenic factors and the isolation
      and culture of capillary endothelial cells (EC) have led to a greater
      understanding of the cellular and biochemical bases of new vessel growth. Until
      recently EC have been the focus of most studies of microvascular growth. However,
      capillaries are not simply tubes of EC but have also a second cellular component,
      the mural cell or pericyte. Little is known about the later stages of vessel
      growth, including the addition of the pericyte to the capillary and its influence
      on EC growth and function. Historically the pericyte was defined by its abluminal
      association with the EC in the capillary. Though the pericyte's function was
      largely unknown, ultrastructural studies led to speculation regarding a role for
      the pericyte in contraction, as a stem cell and in the control of microvascular
      growth. Establishment of methods for the isolation, culture and identification of
      pericytes has permitted investigation into the role of the pericyte. EC and
      pericytes make frequent contact in vivo and co-culture studies of EC and
      pericytes reveal that the two cell types interact in a variety of ways including
      diffusible growth regulators, heterotypic contacts, and gap junctions. This
      intercellular communication is likely to be an important component of the complex
      mechanism(s) controlling microvascular growth and function.

PMID- 1378310
TI  - Extracellular matrix as a solid-state regulator in angiogenesis: identification
      of new targets for anti-cancer therapy.
AB  - Angiogenesis, the growth of blood capillaries, is regulated by soluble growth
      factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic
      mitogens act over large distances to initiate capillary growth whereas changes in
      ECM govern whether individual cells will grow, differentiate, or involute in
      response to these stimuli in the local tissue microenvironment. Analysis of this
      local control mechanism has revealed that ECM molecules switch capillary
      endothelial cells between differentiation and growth by both binding specific
      transmembrane integrin receptors and physically resisting cell-generated
      mechanical loads that are applied to these receptors. Control of capillary
      endothelial cell form and function therefore may be exerted by altering the
      mechanical properties of the ECM as well as its chemical composition.
      Understanding of this mechanochemical control mechanism has led to the
      development of new angiogenesis inhibitors that may be useful for the treatment
      of cancer.

PMID- 1378311
TI  - The role of angiogenesis in tumor growth.
AB  - Experimental and clinical evidence is here assembled in support of the concept
      that the development of a solid tumor progresses from a prevascular phase to a
      vascular phase. The prevascular tumor does not induce angiogenesis, is limited in
      size, and rarely metastasizes. The vascularized tumor induces host microvessels
      to undergo angiogenesis, has the potential to rapidly expand its cell population,
      and has a propensity to metastasize. Thus, angiogenesis is necessary but not
      sufficient for tumor growth and metastasis. Neovascularization of a tumor
      requires that a critical number of its cells have switched to the angiogenic
      phenotype. The mechanisms by which tumor cells become angiogenic, subjects of
      current study, are reviewed here. At least two general categories are recognized:
      (i) angiogenic activity arises from the tumor cell itself in the form of the
      release of angiogenic molecules such as basic fibroblast growth factor; (ii)
      angiogenic activity arises from host cells recruited by the tumor (e.g.
      macrophages), or is mobilized from the extracellular matrix, or requires
      concomitant loss of physiological inhibition of endothelial cell proliferation.
      Accumulating evidence indicates that for most tumors, the switch to the
      angiogenic phenotype depends upon the outcome of a balance between angiogenic
      stimulators and angiogenic inhibitors, both of which may be produced by tumor
      cells and perhaps by certain host cells.

PMID- 1378312
TI  - Mast cells and angiogenesis.
AB  - Much data exists in the literature to suggest a correlation between mast cell
      accumulation and angiogenesis. This correlation exists for normal blood vessel
      growth as well as pathological vessel growth. The recruitment of mast cells to
      sites of angiogenesis is not completely understood. However, once at the site,
      mast cell products may act directly on endothelial cells to stimulate their
      migration and/or proliferation or may act indirectly by degrading connective
      tissue matrix to provide space for neovascular sprouts to form. Understanding the
      role of mast cells in angiogenesis may provide avenues for intervening in and
      manipulating the neovascularization process.

PMID- 1378313
TI  - Mediators of angiogenesis: the biological significance of basic fibroblast growth
      factor (bFGF)-heparin and heparan sulfate interactions.
AB  - The interactions of basic fibroblast growth factor (bFGF) with heparin-like
      molecules appear to be biologically significant. Heparin and heparan sulfate
      protect bFGF from inactivation by heat, extreme pH and protease degradation. At
      the cellular level, bFGF binds to heparan sulfate on the cell surface. Cell
      surface heparan sulfate proteoglycans (HSPG) constitute relatively low affinity
      binding sites for bFGF. Furthermore, binding of bFGF to cell surface HSPG is
      necessary for its binding to high affinity FGF receptors and for its mitogenic
      activity. Thus, bFGF activity requires a dual receptor system composed of a
      classical protein-type tyrosine kinase receptor and a lower affinity
      glycosaminoglycan-type receptor. In addition, bFGF is bound to HSPG in the
      extracellular matrix (ECM). It has been suggested that bFGF may be sequestered in
      ECM as part of a stable insoluble FGF-HSPG complex from which it is released by
      specific enzymatic mechanisms when needed for mitogenic activity.

PMID- 1378314
TI  - Inhibition of angiogenesis.
AB  - The concept of antiangiogenic therapy was first proposed in the early 1970s as a
      method of restricting tumor growth by inhibiting angiogenesis. In subsequent
      years sufficient knowledge about the process of angiogenesis itself was obtained
      so that it is now possible to begin to develop antiangiogenic therapy for
      clinical use. At least three strategies are feasible: (i) inhibition of release
      of angiogenic molecules from tumor cells; (ii) neutralization of angiogenic
      molecules that have already been released; and (iii) inhibition of vascular
      endothelial cells from responding to angiogenic stimulation. Most of the
      angiogenic inhibitors that have been discovered at the time of writing, directly
      interfere with the ability of endothelial cells to form new capillary blood
      vessels. Antiangiogenic activity is a newly found property of alpha-interferon.
      Although alpha-interferon is a relatively weak angiogenesis inhibitor in
      comparison to others, it has been very successful in the treatment of life
      threatening hemangiomas in children. Early clinical experience with this first
      angiogenesis inhibitor to reach clinical trial, indicates that optimal
      antiangiogenic therapy in the future is likely to be based on the long-term use
      of inhibitors with low toxicity, and with little chance of inducing drug
      resistance. It is apparent that different types of angiogenesis inhibitor may be
      administered together and that these compounds may also be administered to cancer
      patients as adjuncts to conventional chemotherapy. It is important to recognize
      that tumor vasculature has other properties besides angiogenesis, which make it a
      potential specific target for anti-cancer therapy.

PMID- 1378315
TI  - Modulation of myeloid proliferation and differentiation by monoclonal antibodies
      directed against a protein that interacts with the interleukin-3 receptor.
AB  - Hematopoietic cells can be transformed through the acquisition of autocrine
      growth factor production. Because of their ability to inhibit autocrine growth,
      antibodies directed against the growth factor or its receptor may have
      therapeutic potential. However, these agents may also inhibit normal cell
      development. We have developed two monoclonal antibodies, 4G8 and 2F2, directed
      against a protein of 110 to 150 Kd that interacts with the interleukin-3 (IL-3)
      receptor (R) complex. These antibodies inhibit IL-3-induced proliferation of
      nonleukemic and leukemic IL-3-dependent cell lines, as well as the autonomous
      growth of WEHI-3B in vitro and in vivo. These results suggest the possibility
      that anti-IL-3R antibodies may be useful in the treatment of some leukemias.
      However, the effect of anti-IL-3R antibodies on normal myeloid development in
      vitro has not been examined. We examined the effect of 4G8 and 2F2 on the growth
      in vitro of colony-forming unit granulocyte-macrophage (CFU-GM) colonies induced
      by IL-3, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage
      CSF (GM-CSF), and macrophage-CSF (M-CSF). Our results show that while 4G8 and 2F2
      inhibited CFU-GM colony formation induced by IL-3, they augmented colony
      formation induced by the other hematopoietins. 4G8 and 2F2 also enhanced G-CSF
      induced proliferation of 32Dc13 and GM-CSF-induced proliferation of PT18,
      confirming that the effect on CFU-GM was a direct effect. Finally, 4G8 and 2F2
      inhibited G-CSF-induced differentiation of 32Dc13, similar to low levels of IL-3;
      yet, neither 4G8 nor 2F2 blocked binding of G-CSF to its receptor. These results
      indicate that, in the absence of IL-3 and in the presence of other
      hematopoietins, 4G8 and 2F2 can function as weak IL-3 agonists. These studies
      suggest that antibodies such as 4G8 and 2F2, directed against components of the
      IL-3R, could potentially augment myeloid growth in vivo, rather than inhibit
      myeloid growth.

PMID- 1378316
TI  - Nonhematopoietic tumor cell lines express stem cell factor and display c-kit
      receptors.
AB  - Human stem cell factor (SCF) acts in the presence of other growth factors to
      stimulate the growth of primitive hematopoietic progenitor cells. These effects
      are performed by activation of the SCF receptor, c-kit. Because of the potential
      use of SCF in patients undergoing chemotherapy and bone marrow transplantation,
      the effect of SCF on nonhematopoietic tumors requires investigation. To determine
      whether human tumor cell lines display c-kit receptors, we performed binding
      experiments with 125I-SCF on a breast carcinoma cell line (Du4475), a gastric
      carcinoma cell line (KATO III), a melanoma cell line (HTT144), as well as two
      small cell lung carcinoma cell lines (H69 and H128). The biologic effect of SCF
      on tumor cell lines was assessed by its ability to stimulate tritiated thymidine
      uptake and to enhance colony growth in methylcellulose. The breast carcinoma cell
      line, Du4475, as well as two small cell lung carcinoma cell lines, H69 and H128,
      exhibit high-affinity c-kit receptors with approximate binding affinities of 40,
      100, and 90 pmol/L, respectively. The number of high-affinity receptors per cell
      ranged from 700 to 9,500. The gastric carcinoma cell line, as well as the
      melanoma cell line, showed trace binding of 125I-SCF. In the presence of SCF
      alone, or in combination with granulocyte-macrophage colony-stimulating factor or
      interleukin-3, there was less than a 17% increase in the colony growth of Du4475,
      H69, or H128 cell lines. Postulating that the lack of growth response could be
      secondary to endogenous SCF production by the tumor cell lines, we used an RNAse
      protection assay to determine whether the tumor cell lines contain SCF messenger
      RNA (mRNA). In addition, we tested tumor cell line supernatants for the presence
      of secreted SCF protein by enzyme immunoassay, and analyzed the tumor cell lines
      for membrane-bound SCF by indirect immunofluorescence. Our results show that the
      Du4475, H69, and H128 cell lines, as well as a melanoma cell line (HTT144), have
      multiple copies of SCF mRNA. Soluble SCF protein was detected in the cell
      supernatants in the Du4475 and H69 cell lines and SCF was found on the surface of
      all four cell lines. These data show that some human solid tumor cell lines
      display high-affinity c-kit receptors and produce SCF, which can be detected on
      the cell surface. These results suggest the possibility that autocrine production
      of SCF by c-kit receptor-bearing tumor cells may enhance cell growth in tumor
      cell lines.

PMID- 1378317
TI  - Effect of stem cell factor on colony growth from acquired and constitutional
      (Fanconi) aplastic anemia.
AB  - The aim of this study was to evaluate the effect of stem cell factor (SCF) on the
      in vitro growth of bone marrow hematopoietic progenitors from patients with
      acquired severe aplastic anemia (AA) or Fanconi's anemia (FA). For this purpose,
      we studied 11 patients with acquired AA (5 at diagnosis, 6 after ALG treatment),
      12 patients with FA, and nine normal controls. Bone marrow cells were plated in
      vitro for colony-forming unit granulocyte-macrophage (CFU-GM) (in the presence of
      granulocyte-macrophage colony-stimulating factor [GM-CSF]), and for burst-forming
      unit-erythroid (BFU-E) and CFU-granulocyte, erythroid, monocyte, megakaryocyte
      (CFU-GEMM) colonies (in the presence of erythropoietin and interleukin-3 [IL-3]),
      with or without 20 ng/mL of SCF. In normal controls, SCF enhanced the growth of
      CFU-GM colonies from 103 to 263 (median), of BFU-E from 168 to 352, and of GEMM
      colonies from 6 to 38/10(5) cells plated. In patients with acquired AA, SCF
      induced a significant enhancement of BFU-E growth (8 to 29; P = .01) and allowed
      the formation of GEMM colonies that were not scored in baseline culture
      conditions (0 to 8; P = .01). CFU-GM growth was enhanced (4 to 20), but not
      significantly (P = .3). This was true both for patients at diagnosis and after
      antilymphocyte globulin treatment. By contrast, 10 of 12 FA patients grew no CFU
      GM, BFU-E, or CFU-GEMM colonies, with or without SCF. In two FA patients (one
      transfusion-dependent and one transfusion-independent), an enhancement of CFU-GM
      and/or BFU-E was observed. The lack of response of hematopoietic progenitor cells
      from FA patients to GM-CSF+SCF or IL-3+SCF was not dependent on a defective
      expression of cytokine receptor messenger RNAs. Northern blot analysis showed in
      marrow cells from acquired AA and FA patients the presence of normal transcripts
      for alpha- and beta-chains of GM-CSF/IL-3 receptor and for c-kit protein. In
      conclusion, SCF promotes the in vitro growth of hematopoietic progenitors in
      patients with acquired AA, but not in patients with FA, pointing out the
      intrinsic nature of the defect in the latter disorder.

PMID- 1378318
TI  - Vascular cell adhesion molecule-1 expressed by bone marrow stromal cells mediates
      the binding of hematopoietic progenitor cells.
AB  - Human bone marrow-derived CD34+ cells were analyzed for the expression of the
      beta 1-family of integrin adhesion molecules. Integrin alpha 4 beta 1 was
      consistently expressed by greater than 90% of CD34+ cells, including essentially
      all assayable granulocyte-macrophage colony-forming cells (CFU-GM) and erythroid
      bursts (BFU-E) as shown by fluorescence-activated cell sorting studies. Adhesion
      of highly enriched CD34+ cells to cultured allogeneic marrow stromal cells was
      largely inhibited both by monoclonal antibody to alpha 4 beta 1 and to vascular
      cell adhesion molecule-1 (VCAM-1), a ligand for alpha 4 beta 1. VCAM-1 was found
      to be expressed by bone marrow stromal elements in vitro both constitutively at
      low level and at high levels after treatment with cytokines. Induction of VCAM-1
      was cytokine- and time-dependent with maximum levels being obtained after 4 hours
      of exposure to a combination of interleukin-4 and tumor necrosis factor-alpha.
      Cytokine-induced stromal cells bound threefold higher numbers of CFU-GM and BFU
      E, this increase being abrogated by anti-alpha 4 beta 1 and anti-VCAM-1
      antibodies. In addition, the adhesion to stroma of more immature progenitors, the
      long-term culture initiating cells, also occurred through an alpha 4 beta 1/VCAM
      1-dependent mechanism. These studies identify an adhesion mechanism of potential
      importance in the localization of primitive progenitors within the hematopoietic
      microenvironment.

PMID- 1378319
TI  - Stem cell factor, interleukin-3, and interleukin-6 promote retroviral-mediated
      gene transfer into murine hematopoietic stem cells.
AB  - The efficiency of retroviral-mediated gene transfer into hematopoietic stem cells
      (HSC) is dependent on the survival and self-renewal of HSC in vitro during
      retroviral infection. We have examined the effect of prestimulation of bone
      marrow with various cytokines, including the product of the Steel gene, Steel
      factor or stem cell factor (SCF) (the ligand for the c-kit receptor) on the
      efficiency of retroviral transduction of the human adenosine deaminase (hADA)
      cDNA into murine HSC. Bone marrow cells were prestimulated for 48 hours with
      hematopoietic growth factors, then cocultivated with the packaging cell line
      producing the ZipPGK-ADA simplified retrovirus for an additional 48 hours with
      continued growth factor exposure. Nonadherant cells from these cocultures were
      injected into lethally irradiated recipients. The content of day 12 colony
      forming unit-spleen (CFU-S12) in SCF/interleukin 6 (IL-6)-prestimulated and
      cocultured bone marrow was more than threefold greater than that of IL-3/IL-6
      prestimulated bone marrow cells. All mice receiving bone marrow cells infected
      with the PGK-ADA virus after prestimulation with IL-3/IL-6 or SCF/IL-6
      demonstrated hADA expression in the peripheral blood after full hematopoietic
      reconstitution. While all recipients of IL-3/IL-6-prestimulated bone marrow
      expressed hADA at 4 months posttransplant, in three independent experiments
      examining a total of 33 mice, in most recipients of SCF/IL-6-prestimulated and
      infected bone marrow cells, the expression of human enzyme was higher than IL
      3/IL-6 mice. Southern blot analysis of DNA from hematopoietic tissues from these
      same mice prepared at least 4 months posttransplantation also demonstrated a
      higher infection efficiency of HSC as measured by proviral integration patterns
      and genome copy number analysis. These results suggest that the higher level of
      hADA expression seen in mice receiving marrow prestimulated with SCF/IL-6 before
      retroviral infection is due to more efficient infection of reconstituting HSC.
      Other growth factor combinations were also studied; however, prestimulation with
      SCF/IL-6 or IL-3/IL-6 appeared optimal. Using retroviral-mediated gene transfer
      and viral integration patterns, Steel factor (SCF) in combination with IL-6
      appears to increase the survival and self-renewal of reconstituting hematopoietic
      stem cells and proves useful in effecting expression of foreign genes in
      transplant recipients. Such pretreatment may also be useful in the application of
      retroviral transfer methods to human cells.

PMID- 1378320
TI  - Expression and function of adhesion molecules on human hematopoietic stem cells:
      CD34+ LFA-1- cells are more primitive than CD34+ LFA-1+ cells.
AB  - Advances in fluorescence-activated cell sorter technology have brought about
      multicolor analysis of cell phenotypes. To clarify the phenotypes of human
      hematopoietic stem cells (HSCs), we initially prepared novel antibodies against
      CD34 and labeled one of them (4A1) with allophycocyanin (APC). With this, we
      analyzed the phenotypes of CD34+ HSCs and showed that primitive HSCs or CD34+CD33
      cells expressed adhesion molecules such as CD43, CD44, CD11a, CD11c, CD18, and
      leukocyte adhesion molecule (LAM-1). The more primitive hematopoietic cells or
      CD34+CD38- cells also expressed CD11a and CD18 with an incidence of 20% to 30%.
      To clarify the role of adhesion molecules in HSCs, we examined the colony forming
      capacity after long-term culture with allogeneic irradiated stromal layers. Among
      CD34+CD33- cells, CD18+ cells gave rise to colony-forming cells (CFCs) on stromal
      layers, but reached a maximum at week 2, after which the number of generated CFCs
      decreased. On the other hand, CD18- cells generated less CFCs than CD18+ cells at
      2 to 3 weeks, but increased after 4 weeks of culture. When CD18 or CD11a antibody
      was added to a coculture system of CD34+CD33- cells with stromal layers, the
      number of generated CFCs decreased significantly compared with the no antibody
      control. Leukocyte function-associated antigen-1 (LFA-1) (CD11a/CD18) was
      expressed on some populations of hematopoietic cells and contributed to the
      proliferation by interacting with stromal cells. However, more primitive cells
      capable of reconstituting hematopoiesis did not express LFA-1. These data provide
      a rationale for the administration of anti-LFA-1 antibody after bone marrow
      transplantation for reducing the graft failure.

PMID- 1378322
TI  - Phenotypical characteristics of acute myelocytic leukemia associated with the
      t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell
      antigen CD19 together with stem cell antigen CD34.
AB  - Twenty-three acute myelocytic leukemia (AML) patients with t(8;21) chromosomal
      abnormality, all classified as M2 (French-American-British [FAB] classification),
      were investigated. Blastic cells from all patients were positive for the stem
      cell-associated antigens, CD34 and HLA-DR, and the immature myeloid antigens,
      CD13 and CD33. The nonblastic leukemic cells expressed the more mature myeloid
      antigens, CD11b and CD15, with loss of the immature phenotype. The incidence of
      positivities for the stem cell-associated antigens, CD34 and HLA-DR, in t(8;21)
      AML cells was significantly higher in comparison with those in other AML showing
      granulocytic differentiation (M2 or M3). AML cells with t(8;21) also showed some
      phenotypic abnormalities. Frequent expression of CD19 was found in the blastic
      population of t(8;21) AML (18 of 23 cases) without other B-cell antigens and Ig
      gene rearrangements. CD19 expression was confirmed by immunocytochemistry and
      Northern blotting. The CD19+ blastic cells coexpressed both CD34 and HLA-DR. In
      addition, CD33+ cells among the blastic fraction in t(8;21) AML cells were fewer
      in number than in those of M2 or M3 AML without t(8;21). Our findings indicate
      that leukemic blasts of t(8;21) AML commonly express CD19 while preserving the
      stem cell-associated antigens, and differentiate into the granulocytic pathway
      with discordant maturation such as low CD33 expression.

PMID- 1378321
TI  - Expression of bcl-2 in Burkitt's lymphoma cell lines: induction by latent Epstein
      Barr virus genes.
AB  - The bcl-2 oncogene blocks programmed cell death (apoptosis). Epstein-Barr virus
      (EBV) can immortalize B lymphocytes into continuously growing lymphoblastoid cell
      lines (LCL) by the coordinate expression of at least 9 latent genes (EBV nuclear
      antigen [EBNA] 1-6, latent membrane protein [LMP], and terminal proteins [TP] 1
      and 2). We analyzed transcription and expression of bcl-2 and latent EBV genes in
      Burkitt's lymphoma (BL) cell lines with a germinal center phenotype (group I) as
      well as activated BL cell lines (group III) and LCLs. We found high expression of
      bcl-2 as well as the full spectrum of latent EBV genes in LCLs and activated
      group III BL cell lines. Group I BL cells expressed little or no bcl-2, EBNA-2,
      and LMP. Superinfection with nondefective EBV or an EBNA-2-defective virus as
      well as transfection with EBNA-2- or LMP-carrying vectors into the EBV-negative
      cell lines RAMOS, DG75, U698, or BJAB induced upregulation of bcl-2 expression.
      The strongest effect on bcl-2 was obtained by transfection with LMP, or infection
      with the nondefective virus. No change of bcl-2 expression was observed with EBNA
      1. Our data indicate that the immortalization capacity of EBV and the growth
      advantage of EBV-positive compared with EBV-negative BL cells in vitro may
      predominantly be mediated via induction of bcl-2 and the main effectors are EBNA
      2 and LMP.

PMID- 1378324
TI  - Molecular breakpoints and platelet counts in chronic myeloid leukemia.

PMID- 1378323
TI  - Band 3 Tuscaloosa: Pro327----Arg327 substitution in the cytoplasmic domain of
      erythrocyte band 3 protein associated with spherocytic hemolytic anemia and
      partial deficiency of protein 4.2.
AB  - Protein 4.2 is a major red blood cell (RBC) protein that interacts with the band
      3 protein and with ankyrin. Inherited deficiencies of this protein are associated
      with spherocytic hemolytic anemia, but the molecular basis of this defect is
      unknown. We have studied the underlying defect in a patient with spherocytic
      hemolytic anemia whose RBCs had a partial (29% +/- 5%) deficiency of protein 4.2.
      We have first studied the binding of normal ankyrin and protein 4.2 to patient
      inside-out vesicles (IOVs) stripped of peripheral proteins. While the binding of
      ankyrin was normal, the predicted maximal binding capacity of patient IOVs for
      band 4.2 was 20% to 33% lower than that of control IOVs, suggesting a defect in
      the cytoplasmic domain of band 3 (cdb3). An additional line of evidence pointing
      to a possible abnormality of band 3 was an abnormal proteolytic digest of cdb3.
      To elucidate the underlying molecular defect, we have cloned and sequenced the
      cDNA coding for cdb3 from the patient. One band 3 allele was found to be normal,
      while clones corresponding to the other allele contained two mutations:
      substitution A----G in nucleotide 166, changing codon 56 from AAG to GAG (Lys---
      Glu), and substitution C----G in nucleotide 980, changing codon 327 from CCC to
      CGC (Pro----Arg). Since the Lys56----Glu56 substitution is found in a common
      asymptomatic variant of the band 3 protein designated band 3 Memphis, we conclude
      that either the Pro327----Arg327 substitution itself, or in combination with the
      band 3 Memphis polymorphism, underlies the abnormal binding of protein 4.2 to
      cdb3 and results in the spherocytic phenotype.

PMID- 1378325
TI  - Nucleotide sequence of a 2 kb plasmid from Pseudomonas cepacia implicated in the
      degradation of phenylcarbamate herbicides.
AB  - The complete nucleotide sequence of a very small plasmid whose presence and level
      in Pseudomonas cepacia have been linked to herbicide resistance is presented. The
      structural features of the plasmid are discussed.

PMID- 1378328
TI  - Alternative secondary structures in the phage G4 origin of the complementary DNA
      strand synthesis: effects of NaCl concentration on the bleomycin-DNA interaction.
AB  - The effects of NaCl concentration on bleomycin-induced cleavages of single-strand
      and double-strand DNA fragments containing the phage G4 origin of complementary
      DNA strand synthesis were investigated. It was found that bleomycin could be used
      as a reagent to analyze secondary and tertiary structures and subtle changes of
      DNA structures. The effects of NaCl concentration on cleavages of single-stranded
      DNA were distinct at every target site, indicating that the diversity of
      topolotical properties of DNA might change the selectivity of the bleomycin
      induced DNA cleavage. These results showed alternative secondary structures
      within and close to the G4 origin of complementary DNA strand synthesis.

PMID- 1378326
TI  - Cytoplasmic domain of P-selectin (CD62) contains the signal for sorting into the
      regulated secretory pathway.
AB  - P-selectin (CD62), formerly called GMP-140 or PADGEM, is a membrane protein
      located in secretory storage granules of platelets and endothelial cells. To
      study the mechanisms responsible for the targeting of P-selectin to storage
      granules, we transfected its cDNA into COS-7 and CHO-K1 cells, which lack a
      regulated exocytic pathway, or into AtT20 cells, which are capable of regulated
      secretion. P-selectin was expressed on the plasma membrane of COS-7 and CHO-K1
      cells but was concentrated in storage granules of AtT20 cells. Immunogold
      electron microscopy indicated that the electron-dense granules containing P
      selectin in AtT20 cells also stored the endogenous soluble hormone ACTH.
      Activation of AtT20 cells with 8-Br-cAMP increased the surface expression of P
      selectin, consistent with agonist-induced fusion of granule membranes with the
      plasma membrane. Deletion of the last 23 amino acids of the 35-residue
      cytoplasmic domain resulted in delivery of P-selectin to the plasma membrane of
      AtT20 cells. Replacement of the cytoplasmic tail of tissue factor, a plasma
      membrane protein, with the cytoplasmic domain of P-selectin redirected the
      chimeric molecule to granules. We conclude that the cytoplasmic domain of P
      selectin is both necessary and sufficient for sorting of membrane proteins into
      the regulated pathway of secretion.

PMID- 1378327
TI  - Differential expression and processing of two cell associated forms of the kit
      ligand: KL-1 and KL-2.
AB  - The c-kit ligand, KL, and its receptor, the proto-oncogene c-kit are encoded,
      respectively, at the steel (Sl) and white spotting (W) loci of the mouse. Both Sl
      and W mutations affect cellular targets in melanogenesis, gametogenesis, and
      hematopoiesis during development and in adult life. Although identified as a
      soluble protein, the predicted amino acid sequence of KL indicates that it is an
      integral transmembrane protein. We have investigated the relationship between the
      soluble and the cell associated forms of KL and the regulation of their
      expression. We show that the soluble form of KL is generated by efficient
      proteolytic cleavage from a transmembrane precursor, KL-1. An alternatively
      spliced version of KL-1, KL-2, in which the major proteolytic cleavage site is
      removed by splicing, is shown to produce a soluble biologically active form of KL
      as well, although with somewhat diminished efficiency. The protein kinase C
      inducer phorbol 12-myristate 13-acetate and the calcium ionophore A23187 were
      shown to induce the cleavage of both KL-1 and KL-2 at similar rates, suggesting
      that this process can be regulated differentially. Furthermore, proteolytic
      processing of both the KL-1 and KL-2 transmembrane protein products was shown to
      occur on the cell surface. The relative abundance of KL-1 and KL-2 is controlled
      in a tissue-specific manner. Sld, a viable steel allele, is shown to encode a
      biologically active secreted mutant KL protein. These results indicate an
      important function for both the soluble and the cell associate form of KL. The
      respective roles of the soluble and cell associated forms of KL in the
      proliferative and migratory functions of c-kit are discussed.

PMID- 1378329
TI  - Degradation of diazinon, chlorpyrifos, isofenphos, and pendimethalin in grass and
      compost.

PMID- 1378330
TI  - Bacterial degradation and utilization of merbromine and fluorescein mercuric
      acetate.

PMID- 1378331
TI  - [Experimental research on the effective mechanism of jianweiling].
AB  - The purpose of this study is to find out the effective mechanism of Jianweiling
      (JWL) in treating some gastrointestinal (GI) diseases. The functions of GI
      movement, bile and pancreatic secretion and intestinal absorption were measured
      after giving JWL to the experimental rats. The results showed that JWL could
      adjust GI movement once it was in abnormal conditions. When the gastrointestine
      was in paralysis under the influence of abdominal operation, JWL could make GI
      myoelectric activity return to normal; and JWL could relax it when the
      gastrointestine was in a cramp state resulted from Neostigmini Methylsulfurici
      injection. In addition, the pancreatic secretion, the amylase activity in
      pancreatic juice and the intestinal absorption for D-xylose in JWL group were
      obviously better than those of the control groups. These results suggested that
      the effective mechanism of JWL on some GI diseases can be realized by adjusting
      and promoting GI functions in various ways.

PMID- 1378332
TI  - Defects in thymocyte differentiation and thymocyte-stromal interactions in the
      trisomy 16 mouse.
AB  - We have examined fetal thymic development in the trisomy 16 (Ts16) mouse, which
      is considered to be a model for human trisomy 21, or Down Syndrome. The Ts16
      thymus contains 10 to 20% of the number of lymphocytes found in a normal thymus
      at a comparable stage. Expression of thymocyte differentiation markers (Thy-1,
      CD5, CD8, CD4, CD3, and HSA) is severely affected in Ts16 fetuses aged 14-18
      gestational days. When thymuses from 14-day Ts16 mice were cultured in vitro,
      these markers eventually reached levels of expression comparable to those seen in
      normal thymuses in culture. On the other hand, expression of CD44 appears to be
      unaffected in Ts16 thymuses in vivo, but declines in vitro relative to normal
      thymuses. Reconstitution of depleted thymic stroma with thymocytes showed
      evidence of defects in both developmental compartments.

PMID- 1378333
TI  - Comparison of immunocytochemical and Holzer's methods for detection of acute and
      chronic gliosis in human postmortem material.
AB  - Immunocytochemical staining for glial fibrillary acidic protein (GFAP) allows
      more specific identification of astrocytes and their processes than classical
      histochemical techniques and has therefore recently been used by some
      investigators to quantify gliosis. However, although the immunocytochemical
      method is superior for delineation of reactive astrocytes, the examples presented
      here and previous work by others demonstrate that chronic fibrillary gliosis may
      be best detected by Holzer's method and not by GFAP immunocytochemistry. The
      authors' studies indicate that if, as in a recent study of gliosis in
      schizophrenia, computer-assisted densitometry is to be used to measure gliosis,
      the immunoperoxidase method may not be a sensitive technique to demonstrate glial
      changes in human postmortem material.

PMID- 1378334
TI  - Cancer chemotherapy and quality of life.

PMID- 1378335
TI  - Current issues in cancer. Biological therapy.

PMID- 1378336
TI  - Indications for aspirin as a palliative for tinnitus caused by SOAEs: a case
      study.
AB  - This paper explores the effect of aspirin on the tinnitus of one patient for whom
      two contralateral spontaneous otoacoustic emissions (SOAEs) caused binaural
      tinnitus. The relation between the SOAEs and tinnitus was explored during a
      preliminary testing session, after which the SOAEs were measured for 7 days.
      During days 1, 2, 5, 6 and 7 of the trial, a placebo (two 50-mg tablets of
      ascorbic acid) was administered four times per day. During days 3 and 4, a drug
      (two 300-mg tablets of aspirin) was administered four times per day. During day
      2, the right ear's SOAE was low level and labile, sometimes disappearing into the
      noise floor. The effect of aspirin on an emission which is not consistently
      observed, cannot be assessed so this report focuses primarily on the left ear.
      During days 1 and 2, the SOAE in the left ear was present and the tinnitus was
      audible. By day 3 (after 2.4 g of aspirin), the SOAE in the left ear had been
      abolished, and the tinnitus was not audible. On the fifth day (24 hours after the
      last aspirin), both the SOAE and the tinnitus in the left ear had returned. There
      were no reported side-effects of the aspirin. Thus, aspirin seemed to provide an
      acceptable palliative for this patient's SOAE-caused tinnitus.

PMID- 1378337
TI  - The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of
      neurogenic inflammation.
AB  - 1. Release of the tachykinin, substance P, from the peripheral terminals of
      polymodal afferent C-fibres is thought to be largely responsible for the
      vasodilatation and plasma protein extravasation described as neurogenic
      inflammation. The effects of CP-96,345, a non-peptide antagonist at the substance
      P (NK1) receptor, on these vascular reactions were investigated in the rat. 2.
      Intravenously (i.v.) injected CP-96,345 (0.4-3.0 mumol kg-1) prevented the drop
      in blood pressure, a measure of the peripheral vasodilatation, evoked by
      substance P and neurokinin A in a dose- and time-dependent manner, but did not
      affect that elicited by the non-tachykinin peptides calcitonin gene-related
      peptide and vasoactive intestinal polypeptide. 3. Plasma protein extravasation
      evoked by i.a. infusion of substance P, antidromic stimulation of the saphenous
      or the vagus nerve, and stimulation of cutaneous afferent nerves with mustard
      oil, were each significantly inhibited by CP-96,345 (3.0-9.0 mumol kg-1, i.v.).
      Furthermore, CP-96,345 was orally active in blocking mustard oil-induced plasma
      extravasation with an ED50 of 10 mumol kg-1. 4. The inhibition of substance P
      induced vasodilatation and of neurogenic plasma extravasation by CP-96,345 was
      stereospecific as the inactive isomer CP-96,344 (2R, 3R enantiomer of CP-96,345)
      had no effect. 5. Thus CP-96,345 is a specific, highly potent, long-acting and
      orally active inhibitor of tachykinin-mediated neurogenic inflammation.

PMID- 1378339
TI  - Mechanism of action of MY-1250, an active metabolite of Repirinast, in inhibiting
      histamine release from rat mast cells.
AB  - 1. When MY-1250 (3.6 x 10(-5) M) was added to mast cells, it caused a rapid
      increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP) and decrease in
      adenosine 5'-triphosphate (ATP), both of which recovered to their original levels
      within 2 min. The accumulation of cyclic AMP was maximal at 20 s after challenge
      with MY-1250. The minimum level of ATP was observed at 20 s after addition of MY
      1250. 2. The initial rise in [Ca2+]i and the histamine release induced by DNP-AS
      antigen (40 micrograms ml-1) was most strongly inhibited at 20 s after incubation
      of the mast cells with MY-1250. 3. MY-1250 strongly and dose-dependently
      inhibited the histamine release from rat mast cells induced by antigen. Moreover,
      MY-125 strongly inhibited calcium ion mobilization from the intracellular Ca(2+)
      store. 4. These results suggested that the inhibitory mechanism of MY-1250 on the
      initial rise in [Ca2+]i and histamine release induced by antigen was due to the
      inhibition of ATP-dependent Ca(2+)-release from the intracellular Ca(2+)-stores.

PMID- 1378340
TI  - The role of cyclic AMP in non-adrenergic non-cholinergic contraction in guinea
      pig bronchi.
AB  - 1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP)
      in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial
      strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by
      electrical field stimulation (EFS) in a concentration-dependent fashion (-log
      EC50 was 7.22 +/- 0.12 M and maximum inhibition was 100 +/- 0.01%). However,
      forskolin (less than 1 microM) did not alter the contraction induced by substance
      P (SP, 1 microM). 3. Dibutyryl cyclic AMP (1 mM) also reduced NANC contractions
      induced by EFS (100 +/- 0.01%) without significant effect on SP (1 microM)
      induced contractions. In contrast, dibutyryl cyclic GMP (1 mM) was without effect
      against either NANC or SP-induced contractions. 4. Both the beta 2-adrenoceptor
      agonist, procaterol (0.1 nM to 3 nM) and theophylline (100 nM to 1 mM)
      concentration-dependently reduced EFS-induced NANC contractions without
      significant effect on SP (1 microM)-induced contractions. 5. In contrast to
      forskolin, procaterol and theophylline, both sodium nitroprusside and cromakalim
      inhibited the EFS-induced contractions only at those concentrations that
      similarly reduced the contractions induced by SP (1 microM). 6. These results
      suggest that cyclic AMP may mediate pre-junctional inhibition of NANC
      contractions in guinea-pig bronchi.

PMID- 1378338
TI  - Induction and potential biological relevance of a Ca(2+)-independent nitric oxide
      synthase in the myocardium.
AB  - 1. We have investigated whether the myocardium and isolated cardiac myocytes can
      express a Ca(2+)-independent NO synthase after treatment with endotoxin or
      cytokines. Nitric oxide synthesis was measured in cytosols from the left
      ventricular wall from rats treated with endotoxin, or from freshly isolated
      myocytes from adult rats treated in vitro with cytokines. 2. Cytosols from the
      ventricle of saline-treated control animals showed only Ca(2+)-dependent NO
      synthesis. After treatment with endotoxin, the expression of an inducible, Ca(2+)
      independent NO synthase was observed. The activity of this enzyme was maximal at
      6 h and returned towards control levels by 18 h; no alterations occurred in the
      Ca(2+)-dependent NO synthase activity. Parallel to this enzyme induction there
      was an increase in myocardial guanosine 3':5'-cyclic monophosphate (cyclic GMP)
      and plasma nitrite and nitrate (NOx-). All these changes were prevented by
      pretreatment of the rats with dexamethasone. 3. Myocytes possessed Ca(2+)
      dependent NO synthase activity and expressed, after treatment with tumour
      necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), a Ca(2+)
      independent NO synthase, the induction of which was prevented by dexamethasone
      and cycloheximide. 4. Since increases in cyclic GMP levels in the heart are
      associated with reduced myocardial contractility, it is possible that the
      enhanced production of NO by a Ca(2+)-independent enzyme accounts, at least in
      part, for the depression of myocardial contractility seen in septic shock,
      cardiomyopathies, allograft rejection, burn trauma, as well as during anti-tumour
      therapy with cytokines.

PMID- 1378341
TI  - Pharmacological and histological examinations of regional differences of guinea
      pig lung: a role of pleural surface smooth muscle in lung strip contraction.
AB  - 1. Parenchymal lung strip preparations have been widely used as an in vitro model
      of peripheral airway smooth muscle. The present study examined functional
      responses of 4 consecutive guinea-pig lung parenchymal strips isolated from the
      central region (segment 1) to the distal edge (segment 4) of the lower lung lobe.
      The middle two segments were designated as segments 2 and 3. 2. Lung segments 1
      and 4 exhibited significantly greater contraction than the other 2 segments to
      KCl when responses were expressed as mg force per mg tissue weight. Contractile
      responses to bronchospastic agents including histamine, carbachol, endothelin-1,
      leukotrienes (LT) B4 and D4, and the thromboxane A2-mimetic U46619 demonstrated
      no significant difference in EC50 values among the 4 lung segments. 3.
      Contractile responses of segments 1 and 4 to antigen-challenge (ovalbumin),
      ionophore A23187 and substance P were significantly greater than the other 2
      segments with respect to either sensitivity or maximum responsiveness. 4. U46619
      induced contractions of the 4 lung segments were relaxed in similar manner by
      papaverine and theophylline up to 100%, salbutamol up to 80%, and sodium
      nitroprusside by only 20%. In contrast, sodium nitroprusside markedly reversed
      U46619-induced contraction of pulmonary arterial rings and bronchial rings. 5.
      Histological studies identified 2-4 layers of smooth muscle cells underlying the
      lung pleural surface. Mast cells were prominent in this area. Moreover,
      morphometric studies showed that segment 4 possessed the least amount of smooth
      muscle structures from bronchial/bronchiolar wall and vasculatures as compared to
      the other 3 segments, and a significant difference in this respect was evident
      between segment 1 and segment 4.6. Since lung segments 1 and 4 are covered with
      larger surface area of lung pleura, the present results suggest that the
      significantly greater intrinsic contractile responses of segments 1 and 4 are
      associated with the presence of increased lung pleural surface possibly together
      with more mast cells. Thus, a primary contribution to the net contraction of the
      lung parenchymal strips may be smooth muscle from the lung pleura, alveolar ducts
      and interstitial contractile cells rather than from bronchi/bronchioles and
      microvasculatures.

PMID- 1378343
TI  - Positive inotropic and negative chronotropic effects of (-)-cis-diltiazem in rat
      isolated atria.
AB  - 1. The cardiovascular effects of (-)-cis-diltiazem, an optical isomer of
      diltiazem, were studied in the isolated atrium and aortic strip. (-)-cis
      Diltiazem (30 microM or more) increased the developed tension of the rat left
      atrium, while (+)-cis-diltiazem (1 microM or more) decreased it. 2. (-)-cis
      Diltiazem (1 to 100 microM) decreased the rate of spontaneous beating in the
      right atrium as did (+)-cis-diltiazem. 3. The potency of the positive inotropic
      action of (-)-cis-diltiazem was almost the same as that of ouabain in the rat
      left atrium, but in the guinea-pig left atrium it was considerably weaker than
      that of ouabain. 4. In both endothelium-intact and endothelium-denuded aortic
      strips, (-)-cis-diltiazem relaxed the Ca(2+)-induced contraction. In the
      endothelium-intact rat aortic strip depolarized by 15 mM KCl, Bay K 8644, a
      calcium channel agonist, increased the contractile force, whereas (-)-cis
      diltiazem did not. 5. These results indicate that (-)-cis-diltiazem has a
      positive inotropic action in isolated atria in rats and guinea-pigs, but the mode
      of positive inotropic action of (-)-cis-diltiazem is different from that of
      ouabain or Bay K 8644.

PMID- 1378344
TI  - Effect of K+ channel-modulating drugs on the vasoconstrictor responses of
      leukotrienes C4, D4 and angiotensin II in the guinea-pig isolated perfused heart.
AB  - 1. The vascular actions of leukotrienes C4 (LTC4) and LTD4 in the guinea-pig
      isolated perfused heart were studied in the presence of potassium (K+) channel
      modulatory compounds. 2. Cromakalim (0.35-10 microM), a K+ channel activator,
      inhibited the vasoconstrictor responses of LTC4 (30 pmol), LTD4 (30 pmol) and
      angiotensin II (AII) (100 pmol) in a concentration-dependent manner. 3. Glyceryl
      trinitrate (10 mgl-1) and vasoactive intestinal peptide (10 nM) induced a similar
      vasodilator action to cromakalim in the isolated heart but had no effect on
      responses to LTC4 and LTD4. 4. The inhibitory action by cromakalim (10 microM) on
      the LTC4 (30 pmol) response could be reversed in the presence of an equimolar
      concentration of glibenclamide. However, glibenclamide (10 microM) only partially
      restored the LTD4 (30 pmol) actions. 5. Galanin (10 nM) and charybdotoxin (60 nM)
      had no effect on the vascular responses to LTC4 and LTD4 (30 pmol). 6. Inhibition
      by cromakalim of coronary vasospasm induced by vascular LTC4, LTD4 and AII
      appears to be separate from its vasodilator action and it is postulated that a
      cromakalim-sensitive mechanism in the coronary vasculature is important in the
      vasoconstrictor responses to LTC4, LTD4 and AII.

PMID- 1378345
TI  - Flow cytometry and rheumatic disease.

PMID- 1378346
TI  - Multiphasic effect of morphine on the release of substance P from rat trigeminal
      nucleus slices.
AB  - It is generally accepted that morphine acts presynaptically to inhibit substance
      P (SP) release from afferent terminals in the trigeminal nucleus. Recent studies,
      however, provide evidence that opioids produce both inhibitory and excitatory
      effects on SP release which are concentration- and receptor subtype-dependent. In
      the present study, we have examined a wide range of morphine concentrations on
      K(+)-evoked SP release from rat trigeminal nucleus caudalis slices.
      Immunoreactive SP was measured in perfusates. Morphine produced multiphasic
      effects on K(+)-evoked SP release without affecting basal release. A very low
      nanomolar concentration (1 nM) suppressed release, higher nanomolar
      concentrations (100-300 nM) facilitated release, a low micromolar concentration
      (3 microM) suppressed release, and a higher micromolar concentration (30 microM)
      facilitated release. These effects were abolished by opioid receptor blockade
      with naloxone (30 nM). Thus, morphine produces a complex bi-directional
      modulation of SP release from TNC which is concentration- and possibly receptor
      subtype-dependent.

PMID- 1378342
TI  - Alpha 4-2 beta 2 and other nicotinic acetylcholine receptor subtypes as targets
      of psychoactive and addictive drugs.
AB  - 1. Xenopus oocytes were injected with various muscle and neuronal nicotinic
      acetylcholine receptor (ACh receptor, cholinoceptor) subunit RNA combinations and
      their pharmacological properties studied using two-electrode voltage clamp. The
      functional expression of one of these combinations, rat alpha 4-2 beta 2, has not
      been previously described. The alpha 4-2 mRNA is a splicing variant transcribed
      from the alpha 4 gene. In the experiments reported here, the alpha 4-2 beta 2
      subtype was functionally indistinguishable from the alpha 4-1 beta 2 subtype. 2.
      For each subtype, the relative potency of nicotine compared with acetylcholine
      was obtained by estimating the relative concentration of nicotine which would
      elicit the same current response as 0.1 microM Ach. The ratios of these
      concentrations (nicotine: ACh) for the mouse muscle ACh receptor-(alpha 1 beta 1
      gamma delta) was 96.1:1. In contrast, the ratios for the rat neuronal subtypes
      were: alpha 2 beta 2, 1.01:1; alpha 3 beta 2, 2.01:1; alpha 4 beta 2, 0.76:1 and
      alpha 4-2 beta 2, 0.76:1. The much greater relative nicotine sensitivity of the
      neuronal subtypes as compared with muscle receptors illustrates their potential
      to mediate the psychoactive and addictive effects of nicotine. However, it does
      not appear that the differences in relative nicotinic sensitivity among the
      neuronal receptors themselves can be used as a simple discriminative tool in
      neuronal tissue. 3. The slopes of the log dose-log response curves at low ACh
      concentrations were all greater than 1 but less than 2, suggesting that at least
      two agonist binding sites mediate the functional response of each hetero
      oligomer. 4. The response of all the neuronal subtypes to ACh could be inhibited
      by the psychoactive drugs mecamylamine, amitriptyline, phencyclidine,
      trifluoperazine and promethazine. With the exception of the very potent
      antagonist, mecamylamine, the degree of block of the peak current to ACh produced
      by 10 microM concentrations of these drugs was remarkably similar (around 50%).
      5. The degree of inhibition produced when the antipsychotic drug,
      trifluoperazine, was co-applied with ACh increased as the duration of application
      increased. Such an effect was not observed with promethazine, a related
      phenothiazine derivative which does not have antipsychotic actions.

PMID- 1378347
TI  - Morphine produces a multiphasic effect on the release of substance P from rat
      trigeminal nucleus slices by activating different opioid receptor subtypes.
AB  - Morphine (MOR) produces a concentration-dependent multiphasic effect (inhibitions
      and facilitations) on K(+)-evoked substance P (SP) release from rat trigeminal
      nucleus slices. In this study, we tested the action of selective opioid receptor
      antagonists on this multiphasic effect of MOR. 1 nM MOR produced an inhibition of
      K(+)-evoked release of SP that was affected only by the selective mu 1-opioid
      receptor antagonist naloxonazine (1 nM). MOR at 100 nM elicited an increase in SP
      release which was abolished selectively by the mu-opioid receptor antagonist,
      beta-funaltrexamine (beta-FNA; 20 nM) and attenuated by the delta-opioid receptor
      antagonist, ICI 174,864 (0.3 microM). 3 microM MOR produced an inhibition of SP
      release that was reversed only by ICI 174,864 (0.3 microM). MOR at even higher
      concentrations (30 microM) produced an enhancement of SP release that was
      reversed selectively by 3 nM n-binaltorphimine (n-BNI; 3 nM), a kappa-opioid
      receptor antagonist. In slices pretreated with 20 nM beta-FNA and in the presence
      of 0.3 microM ICI 174,864 (mu- and delta-opioid receptor blockade), both 100 nM
      and 3 microM MOR elicited a strong facilitation of K(+)-evoked SP release which
      was sensitive to 3 nM n-BNI. Thus, the increase in SP release produced by 100 nM
      may be mediated by the simultaneous stimulation of beta-FNA-sensitive mu- and
      excitatory delta-opioid receptors whereas the facilitation of SP release induced
      by 30 microM MOR could be due to the activation of kappa-opioid receptors. 1 nM
      and 3 microM MOR may inhibit SP release by stimulating naloxonazine-sensitive mu
      1- and inhibitory delta-opioid receptors, respectively.

PMID- 1378348
TI  - Effect of peptidase inhibition on the pattern of intraspinally released
      immunoreactive substance P detected with antibody microprobes.
AB  - Antibody microprobes bearing antibodies to the C-terminus of substance P (SP)
      were used to measure release of immunoreactive (ir) SP in the dorsal horn of
      barbiturate anaesthetized spinal cats. Electrical stimulation of unmyelinated
      primary afferents of the ipsilateral tibial nerve produced a relatively localised
      release of ir SP in the superficial dorsal horn. Prior microinjection of the
      peptidase inhibitors kelatorphan and enalaprilat in the dorsal horn resulted in
      ir SP being detected over the whole of the dorsal horn and the overlying dorsal
      column. This pattern had previously been observed with evoked release of ir
      neurokinin A and supports the proposal that a slow degradation results in a
      neuropeptide accessing many sites remote from sites of release.

PMID- 1378349
TI  - The medial dorsal nucleus is one of the thalamic relays of the cerebellocerebral
      responses to the frontal association cortex in the monkey: horseradish peroxidase
      and fluorescent dye double staining study.
AB  - To reveal the thalamic relay nucleus of the cerebellocerebral responses in the
      frontal association cortex, simultaneous labeling of the cerebellothalamic (C-T)
      terminals and the thalamocortical (T-Cx) neurons was performed in three monkeys.
      Horseradish peroxidase (HRP) was injected into the deep cerebellar nuclei and
      small doses of HRP or fluorescent dye were injected into the prefrontal cortex.
      The distribution of anterogradely labeled C-T terminals and retrogradely labeled
      T-Cx neurons was examined in the same sections. In addition to being distributed
      in the ventral thalamic nuclei and nucleus X, as previously reported,
      anterogradely labeled terminals were distributed in the ventrolateral part of the
      medial dorsal (MD) nucleus where retrogradely labeled thalamo-frontal projection
      neurons were localized. This study revealed that the ventrolateral parts of the
      MD together (MDmf, MDpc and MDdc) form one of the thalamic relays of the
      cerebelloprefrontal responses.

PMID- 1378350
TI  - Distribution of clusterin in Alzheimer brain tissue.
AB  - The immunohistochemical distribution of clusterin (SP40,40, SGP-2) was determined
      in Alzheimer disease (AD) and normal human brain tissue and compared with the
      distributions of vitronectin, protectin and the complement membrane attack
      complex (MAC). Antibodies to all four proteins showed staining of dystrophic
      neurites and neuropil threads in AD tissue, and residual serum in normal tissue,
      but only antibodies to clusterin and vitronectin strongly stained amyloid
      deposits in senile plaques. The clusterin antibody also showed punctate staining
      of some normal appearing AD pyramidal neurons, and very scattered staining of
      intracellular neurofibrillary tangles. Clusterin, vitronectin and protectin are
      all believed to inhibit membrane insertion by the MAC, and these data are
      consistent with upregulation of all three proteins in response to MAC formation
      in AD, and with a neuronal origin of clusterin.

PMID- 1378352
TI  - Back to the future: new theories on 5-fluorouracil/interferon interactions.

PMID- 1378351
TI  - Possibilities for active immunotherapy of human cancer.

PMID- 1378353
TI  - Carcinoid tumor localized in the liver--two cases report: immunohistochemical and
      ultrastructural studies.
AB  - Two cases of carcinoid tumors, considered to be probably hepatic in origin,
      occurring in a 53-year-old man and a 69-year-old woman are reported. In both
      cases no endocrine syndrome appeared, and an alternative primary source of the
      tumor was not found in case two, despite an intensive search at operation. The
      neoplasms in both cases were soft, firm, brown-pink and well-encapsulated. They
      were composed of small uniform cells, that had distinct borders and grew in
      insular, nests, trabeculae and strands that were separated by a delicate fibrous
      stroma. Stains of argentaffin and argyrophil showed strong positivity in both
      cases. The immunohistochemical and ultrastructural studies all demonstrated
      characteristics of a carcinoid. The postoperative recovery was good. They have
      remained well 5 years later in case 1 and 3 years in case 2 after surgical
      treatment. Literature concerning this rare condition is also reviewed.

PMID- 1378356
TI  - [Anaphylactic reaction after dextran administration. Therapy of the reaction].

PMID- 1378355
TI  - Inhibition of production of monocyte/macrophage-derived angiogenic activity by
      oxygen free-radical scavengers.
AB  - We showed previously that thiol-containing compounds inhibited the production of
      macrophage-mediated angiogenic activity. Since thiol-containing compounds may act
      on macrophages by affecting activation and inhibiting the production of oxygen
      free-radicals, we studied the effects of oxygen free-radical scavengers on
      production of angiogenic activity by elicited mouse peritoneal macrophages and
      lipopolysaccharide stimulated normal human monocytes. Monocyte/macrophage
      conditioned media were potently angiogenic when assayed in rat corneas, while
      conditioned media, from oxygen free-radical scavenger-treated cells were not. The
      inhibitory effect of oxygen free-radical scavengers was due to a direct effect on
      monocyte/macrophage production of angiogenic activity but was not due solely to a
      decrease in the production of the macrophage-derived angiogenic cytokine tumor
      necrosis factor-alpha. We conclude that oxygen free-radical scavengers are potent
      inhibitors of the production of macrophage-mediated angiogenic activity.

PMID- 1378357
TI  - [Use of fetoplacental antigens in prenatal diagnosis].

PMID- 1378354
TI  - Plasticity in expression of calcitonin gene-related peptide and substance P
      immunoreactivity in ganglia and fibres following guanethidine and/or capsaicin
      denervation.
AB  - This study was designed to investigate the effects of multiple denervation
      procedures on calcitonin gene-related peptide- and substance P-immunoreactive
      neurons in sympathetic and sensory cranial ganglia and in selected targets.
      Sympathectomy by long-term guanethidine treatment induced a pronounced increase
      in calcitonin gene-related peptide-immunoreactive and substance P-immunoreactive
      nerve fibres in all the tissues investigated, in contrast to a significant
      reduction of immunoreactive cell bodies. Neonatal capsaicin treatment abolished
      substance P immunoreactivity in many targets and caused a dramatic reduction of
      substance P-immunoreactive sensory nerve cell bodies; calcitonin gene-related
      peptide-immunoreactive nerve density was decreased, but the number of
      immunoreactive nerve cell bodies was unchanged. Guanethidine treatment of
      capsaicin-injected rats reversed the loss of calcitonin gene-related peptide
      immunoreactive nerves, but not that of substance P-immunoreactive neurons. In the
      iris, capsaicin treatment had little effect on calcitonin gene-related peptide-
      and substance P-immunoreactive nerves, suggesting that in rats the majority of
      these fibres originate from capsaicin-insensitive neurons. The results suggest
      that the denervation procedures used in this study alter the synthesis and
      transport of neuropeptides in sensory neurons in conjunction with changes in the
      number of nerve fibres.

PMID- 1378358
TI  - Gap junctional channels in adult mammalian sinus nodal cells. Immunolocalization
      and electrophysiology.
AB  - The subcellular mechanism of cell-to-cell communication in the natural pacemaker
      region of the mammalian heart was studied using electrophysiological and
      immunofluorescence techniques in isolated pairs of rabbit sinus nodal cells. By
      measuring whole-cell currents using a double patch-clamp approach, it was
      demonstrated that communication in the sinus node is mediated through gap
      junctional channels similar to those in other types of adult cardiac cell pairs.
      Macroscopic sinus nodal junctional resistance had a mean value of 387.9 +/- 97.1
      M omega (mean +/- SEM, n = 10) and was greatly increased by superfusion with
      alkanols. Single-channel junctional conductance could be resolved in three cell
      pairs. Given their high membrane resistance (1.16 +/- 0.32 G omega, n = 12), the
      electrical coupling provided by as few as three gap junctional channels between
      nodal cells will allow for pacemaker synchronization. Further evidence for the
      presence of the channels was obtained from immunofluorescent double-labeling of
      desmin and the gap junction protein (connexin43) in sinus nodal tissue as well as
      in cultured sinus nodal cells. Using antisera against residues 243-257 of the
      connexin43 protein, a specific staining at the site of cell-to-cell apposition
      was demonstrated. These data provide direct evidence in favor of electronic
      coupling as the means for achieving pacemaker synchronization in the rabbit sinus
      node.

PMID- 1378359
TI  - Acidic and basic fibroblast growth factors in adult rat heart myocytes.
      Localization, regulation in culture, and effects on DNA synthesis.
AB  - Basic fibroblast growth factor (bFGF) and acidic fibroblast growth factor (aFGF)
      are involved in the induction of embryonic mesoderm, angiogenesis, neuronal
      differentiation, and proliferation and survival of many cell types. In cardiac
      myocytes their roles are not well understood. Effects of fibroblast growth
      factors on reexpression of fetal actin genes have been reported. In freshly
      isolated adult rat cardiac myocytes, bFGF mRNA was not detectable by in situ
      hybridization, although the cells contained significant amounts of bFGF and aFGF
      as quantified by radioimmunoassays, mitogen assays with immunoneutralization, and
      Western blotting. After culturing, bFGF mRNA was detected (aFGF mRNA was not
      studied), and the cells contained 2.5-fold more bFGF and 60% more aFGF than
      freshly isolated cells. The FGFs were not found in conditioned medium. They were
      localized, especially in cultured cells, to the nucleus. Cultured myocytes bound
      fourfold more 125I-FGF than freshly isolated cells and expressed the fibroblast
      growth factor R-1 (flg) gene. The addition of bFGF or aFGF in serum-free medium
      to pure populations of myocytes (after 10 days in culture, at which time they are
      spread, beating, and multinucleated) led to increased thymidine incorporation.
      Expression of fibroblast growth factors and fibroblast growth factor receptors by
      adult cardiac myocytes that survive the shock and "dedifferentiation" of
      culturing may contribute to DNA synthesis and, by analogy, to other cell types,
      to regulation of ribosomal and actin genes, and to cell survival. These
      possibilities and their in vivo relevance will require further study.

PMID- 1378360
TI  - Balloon injury and interleukin-1 beta induce nitric oxide synthase activity in
      rat carotid arteries.
AB  - Experiments were performed to investigate whether balloon injury induces nitric
      oxide synthase activity in the blood vessel wall. Contractions to phenylephrine
      were compared in left carotid arteries of the rat, previously injured by balloon
      catheterization and excised either immediately (t = 0), 6, or 24 hours after the
      procedure, with those in control right carotid arteries (with and without
      endothelium). Phenylephrine evoked comparable concentration-dependent
      contractions in balloon-injured (t = 0) and control carotid arteries without
      endothelium, whereas those in control arteries with endothelium were depressed.
      In the balloon-injured carotid arteries (6 and 24 hours), the concentration
      contraction curves to phenylephrine were shifted to the right compared with those
      observed in balloon-injured arteries (t = 0). In balloon-injured carotid arteries
      (6 hours), the hyporeactivity to phenylephrine was enhanced by superoxide
      dismutase. In balloon-injured carotid arteries (24 hours), nitro-L-arginine and
      methylene blue restored full contractions, whereas superoxide dismutase
      potentiated the hyporesponsiveness to phenylephrine. The depressed contractions
      were associated with a concomitant increase in the basal level of cGMP; this
      production was abolished by nitro-L-arginine. The depression of the concentration
      contraction curves to phenylephrine and the increase of the tissue level of cGMP
      induced by interleukin-1 beta (4 hours) were more pronounced in balloon-injured
      arteries (24 hours) than in control arteries without endothelium. The effects of
      interleukin-1 beta were inhibited by nitro-L-arginine. These observations
      indicate that in vivo endothelial injury of the rat carotid arteries induces the
      production of nitric oxide from L-arginine in the blood vessel wall, an effect
      which is potentiated by interleukin-1 beta.

PMID- 1378361
TI  - Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat
      heart.
AB  - To examine whether stimulation of alpha-adrenergic receptors may affect the
      oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE)
      and the alpha-adrenergic agonist norfenephrine were used. NE was administered as
      a continuous intravenous infusion in awake rats for 3 days. It stimulated the
      activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and
      regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the
      highest dose (0.2 mg.kg-1.hr-1), there was also a time-dependent enhancement. The
      increase observed after 48 hours was attenuated partially by the beta-receptor
      blocker metoprolol and the alpha-receptor blocker prazosin. It was entirely
      abolished when both drugs were administered. Carvedilol, a beta-adrenergic
      blocker and vasodilator with alpha 1-blocking activity (0.5 mg.kg-1.hr-1),
      prevented the NE-induced increase in cardiac G-6-PD activity, in functional
      parameters (heart rate, left ventricular systolic pressure, and left ventricular
      dP/dtmax), and in the heart weight/body weight ratio. The alpha-adrenergic
      stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented
      this stimulation. NE and norfenephrine also elevated the available pool of
      cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac
      myocytes freshly isolated from the left ventricle of rats that had received NE
      infusion for 3 days (12.3 +/- 1.4 units/g protein) compared with control rats
      (1.5 +/- 0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase,
      one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7
      +/- 0.7 to 19.1 +/- 1.4 units/g protein. Combined alpha- and beta-receptor
      blockade with carvedilol attenuated these effects.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1378362
TI  - Monoclonal antibody epitopes of mycobacterial 65-kD heat-shock protein defined by
      epitope scanning.
AB  - The binding sites for MoAbs to the 65-kD heat-shock protein (hsp65) of
      mycobacteria have been investigated by epitope scanning. Five hundred and twenty
      six 8-mer peptides representing the complete sequence of Mycobacterium
      tuberculosis hsp65 were synthesised in duplicate using the Epitope Scanning Kit
      (CRB Ltd.). The epitopes of six MoAbs raised to the hsp65 of M. tuberculosis or
      M. leprae were investigated. We have identified the epitope of a new MoAb (DC16);
      this epitope is continuous, hydrophilic in nature and 11 amino acids long. We
      have also confirmed the location of the epitopes of three MoAbs (IIH9, ML30 and
      IIC8). Thus the epitope scanning technique has proved suitable for the detection
      of continuous epitopes of hsp65.

PMID- 1378363
TI  - CD3+ CD57+ lymphocytes are not likely to be involved in antigen-specific
      rejection processes in long-term allograft recipients.
AB  - Cytofluorometric investigation of peripheral blood lymphocytes in 380 long-term
      (greater than 1 year posttransplantation) allograft recipients showed a
      significant increase in the proportion of CD3+57+ lymphocytes (greater than 20%)
      in 20% of patients with renal allografts, 66% of patients with cardiac allografts
      and 44% of patients with liver allografts. Most of these CD3+57+ cells expressed
      the CD8 antigen and a variable proportion the HLA-DR antigen. A retrospective
      analysis showed a poorer prognosis for the clinical outcome in those patients
      with elevated numbers of CD3+57+ cells in peripheral blood. However, CD57+
      lymphocytes could rarely be detected in renal infiltrates by immunohistology.
      Using the Southern blot technique to analyse the T cell receptor rearrangement of
      separated CD57+ cells, no clonal or oligoclonal expansion of T cell clones could
      be detected. Nevertheless, there might be a bias towards the use of particular
      TCR-V beta gene families in at least some patients, as shown by analysis with
      monoclonal antibodies. In summary, CD57+ T cells are not likely to be directly
      involved in the rejection process. The data support the idea of a polyclonal
      and/or superantigen-driven expansion, but not of an antigen-driven expansion of
      these cells.

PMID- 1378366
TI  - [CSF monoamine metabolites in patients with progressive supranuclear palsy].
AB  - Neurochemical abnormalities in the patients with progressive supranuclear palsy
      (PSP) are not well understood. We investigated CSF levels of the monoamine
      metabolites HVA, 5HIAA and MHPG in 5 patients with PSP in order to investigate,
      especially dopaminergic, serotonergic and noradrenergic metabolism. Results were
      as follows (value; mena +/- S.D.). [table: see text] The levels of HVA were
      significantly lower than those in controls. These findings suggest that there is
      a hypofunction of dopaminergic neurons in PSP patients.

PMID- 1378364
TI  - IgG antibodies from patients with primary Sjogren's syndrome and systemic lupus
      erythematosus recognize different epitopes in 60-kD SSA/Ro protein.
AB  - Five synthetic peptides corresponding to the N-, the C- and a central domain in
      60-kD SSA/Ro protein were prepared and tested with sera from 112 patients with
      systemic lupus erythematosus (SLE), 55 with primary Sjogren's syndrome (pSS) and
      29 with rheumatoid arthritis. Among these five fragments, one representing
      residues 21-41, was recognized by antibodies in 57% of pSS patients.
      Interestingly, this peptide was recognized by only a few (less than or equal to
      7%) of SLE sera, while 63% of pSS sera and 46% of SLE sera tested in parallel
      possessed antibodies reacting in ELISA with purified 60-kD SSA protein. The ELISA
      results were compared with the pattern of reactivity obtained in immunodiffusion
      and immunoblotting. The results indicate that the sensitivity of ELISA using
      peptide 21-41 and pSS sera was in the same range as immunoblotting and higher
      than immunodiffusion. Thus the peptide 21-41 proved useful for the detection of
      anti-SSA antibodies in the sera of patients with pSS. Furthermore, a positive
      ELISA using peptide 21-41 could be of potential use to discriminate pSS with
      systemic features from SLE. The fact that peptide 21-41 is recognized by
      antibodies in pSS but only by very few SLE sera implies that different mechanisms
      are involved in the anti-SSA immune response in these two autoimmune diseases.

PMID- 1378365
TI  - Adhesion molecule expression in Graves' thyroid glands; potential relevance of
      granule membrane protein (GMP-140) and intercellular adhesion molecule-1 (ICAM-1)
      in the homing and antigen presentation processes.
AB  - To assess the potential role of adhesion molecules in the pathogenesis of Graves'
      disease, we examined the expression of several of these adhesion molecules,
      including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule (VCAM-1) and granule membrane protein-140 (GMP-140), in sections of
      Graves' thyroid glands and control thyroids, using immunohistochemical
      techniques. Up-regulated expression of GMP-140 was frequently observed on
      endothelial cells (EC) of post-capilliary venules in all Graves' thyroids
      examined, compared with an occasional weak staining on EC control glands. Some
      capillary EC around thyroid follicles (perifollicular EC) were strongly positive
      for GMP-140 in the Graves' thyroids in contrast to a negative staining on the
      same structures in the control glands. In addition, there was a correlation
      between the reactivity and frequency of GMP-140 expression on EC and the severity
      of mononuclear cell (MNC) infiltration in the Graves' thyroids. The expression of
      ICAM-1 was up-regulated on perifollicular EC and EC of small venules in some
      thyroids of both Graves' and control groups. Conversely, no significant
      expression was observed on any type of EC for both endothelial-leucocyte adhesion
      molecule-1 (ELAM-1) and VCAM-1. However, dendritic-like cells, present within
      lymphocytic infiltrates, were positive for VCAM-1 in most of the Graves' thyroids
      examined, especially in those with a severe lymphocytic infiltration. Thyrocytes
      were constantly negative for the expression of all four adhesion molecules
      investigated. These data suggest that GMP-140, as well as ICAM-1, could play an
      important role in the initiation of MNC infiltration in Graves' disease. ELAM-1
      and VCAM-1 appear not to be relevant for the migration of MNC from the blood
      vessels into the target gland, although VCAM-1 expression on dendritic-like cells
      might play an additively tissue-selective role in autoantigen presentation and
      subsequent elicitation of autoimmune phenomena.

PMID- 1378368
TI  - Entry of ADP-ribosylating toxins into cells.

PMID- 1378367
TI  - Mapping of binding sites for monoclonal antibodies to chick tropoelastin by
      recombinant DNA techniques.
AB  - A fusion molecule consisting of the entire coding sequence of mature chicken
      tropoelastin preceded by 14 amino acids of the signal peptide and 9 amino acids
      of vector origin has been expressed in a recombinant bacterial system and
      purified. The molecule has been used as immunogen for the production of
      hybridomas. Monoclonal antibodies which bound specifically the immunogen were
      also reactive with tropoelastin purified from chick aorta and stained elastic
      fibers in aorta sections by immunofluorescence. The region of tropoelastin
      containing the antigenic determinant recognized by each antibody has been
      identified by a recombinant DNA expression strategy based on the use of cDNA
      clones spanning different portions of the coding sequence. It could be shown that
      several antibodies were directed against unique epitopes; among these, a group of
      antibodies bound specifically to the sequence (PGVGV)n. Other antibodies were
      found to recognize antigenic determinants present more than once in the molecule.
      The monoclonal antibodies thus characterized will be useful reagents in studying
      the function of the different domains of tropoelastin.

PMID- 1378370
TI  - Suicide and antidepressants.
AB  - Depression is associated with a risk of suicide 13 to 30 times greater than in
      the general population, and antidepressants are among the drugs most frequently
      implicated in fatal overdose, resulting in a dilemma for the clinician. Suicidal
      thoughts are a core symptom of depression, and there is evidence that the
      selective serotonin (5-hydroxytryptamine) reuptake inhibitors (SSRIs), including
      fluvoxamine, are of particular benefit in reducing their occurrence. Data from
      controlled studies indicate that the SSRIs do not exacerbate suicidal ideation;
      on the contrary, SSRIs protect against the emergence of suicidal thoughts, which
      reflect the natural history of the disease. The SSRIs also appear to be
      particularly effective in patients who are highly suicidal at treatment
      initiation, and to be more effective than the tricyclic antidepressants in
      treating severe depression and improving anxiety symptoms associated with
      depression. Thus, fluvoxamine, in common with other SSRIs, is of particular
      benefit in treating depression in patients with prominent suicidal thoughts or
      who are at increased risk of suicide.

PMID- 1378369
TI  - Comparative efficacy of antidepressants.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are a recently developed class of
      drugs with significantly greater antidepressant efficacy than placebo. Generally,
      in double-blind comparative trials, all SSRIs demonstrated antidepressant
      efficacy similar to that of the 'standard' tricyclic antidepressants
      amitriptyline and imipramine; a meta-analysis of controlled trials found the
      efficacy of the SSRIs to be equivalent to that of the 2 tricyclics. Nevertheless,
      because of small patient numbers included in most studies that compare SSRIs with
      other antidepressants, no definitive statements about relative efficacy can be
      made. In these studies it is simply possible to state that no statistically
      significant differences were identified between SSRIs and the comparative
      antidepressants. Importantly, differences in clinical characteristics exist
      between the SSRIs-differences in elimination half-life (t1/2 beta) between
      fluoxetine and/or its metabolite (total t1/2 beta = 330 hours) and other SSRIs
      (t1/2 beta range = 15 to 30 hours), for example. This has implications in terms
      of potential drug interactions and must be considered when patients have to be
      switched to treatment with monoamine oxidase inhibitors. Studies with fluvoxamine
      have been conducted in both in- and outpatients, whereas trials with other SSRIs
      have been confined largely to outpatient populations. Fluvoxamine has been
      associated with a high incidence of nausea (37%), although this may have resulted
      from high initial dosages (rather than upward dose titration protocols) used in
      early trials. Of further interest, fluoxetine doses of 20mg may be sufficient to
      produce a satisfactory antidepressant response, and this SSRI may be particularly
      useful in patients with chronic retarded depression. More clinical data are
      required before the efficacy of sertraline and citalopram relative to standard
      antidepressants can be clearly defined. Preliminary data indicate that SSRIs are
      effective in the treatment of panic disorder, obsessive-compulsive disorder
      (OCD), eating (e.g. anorexia and bulimia) and personality disorders (e.g. anger,
      impulsiveness) and substance abuse (e.g. alcoholism); early results with
      fluvoxamine in the treatment of panic disorder and OCD, and with fluoxetine in
      the treatment of bulimia, personality disorders and alcohol abuse, have been
      encouraging. SSRIs have a more favourable tolerability profile than tricyclic
      antidepressants and, unlike the tricyclics, are not associated with
      anticholinergic adverse effects, sedation, cardiotoxicity or weight gain. SSRIs
      are associated with a relatively high incidence of nausea, particularly if high
      doses are used at the start of treatment. However, the incidence of nausea
      appears to decrease as treatment is continued.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1378372
TI  - Efficacy of fluvoxamine in severe depression.
AB  - The therapeutic efficacy of fluvoxamine has been demonstrated in large numbers of
      patients participating in comparative double-blind placebo-controlled studies
      using imipramine as the active reference compound. Overall, patients treated with
      fluvoxamine for 4 to 6 weeks had significant amelioration of their depression
      compared with placebo-treated patients. More importantly, the response rate in
      patients with severe depression was greater than in patients with mild or
      moderate depression. However, several investigators have observed high placebo
      response rates, and in some studies there has been a similar response rate to
      imipramine and placebo treatment. While the high placebo response rate may have
      resulted from methodological problems, the issue does raise some questions that
      can only be resolved by further investigation.

PMID- 1378371
TI  - Pharmacological differences of serotonin reuptake inhibitors and possible
      clinical relevance.
AB  - Depression is a heterogeneous disease state characterised by complex alterations
      in several CNS neurotransmitter and receptor systems. All antidepressants are
      thought to act by causing postsynaptic adaptive changes (e.g. in transducers or
      second messengers) within these systems. Thus, the mechanism of action of
      selective serotonin reuptake inhibitors (SSRIs) cannot simply be explained in
      terms of inhibition of serotonin (5-hydroxytryptamine) [5-HT] reuptake.
      Fluvoxamine, sertraline and fluoxetine downregulate central beta-adrenoceptors,
      and all SSRIs are believed to normalise central 5-HT1A- and 5-HT2-receptor
      density and function in patients with depression. SSRIs are as effective as
      tricyclic antidepressants in the treatment of depression, but have distinct
      tolerability advantages--they are not associated with anticholinergic adverse
      effects, cardiotoxicity, sedation or weight gain. However, gastrointestinal
      reactions (e.g. nausea, diarrhoea/loose stools, constipation) are relatively
      common during SSRI therapy. Additionally, in contrast to tricyclic
      antidepressants, SSRI dosage adjustments appear to be unnecessary in elderly
      depressed patients. Fluvoxamine has a much shorter elimination half-life than
      fluoxetine and its active metabolite, norfluoxetine, and therefore a reduced
      potential for drug interactions. Only small amounts of fluvoxamine and
      fluoxetine, but large quantities of paroxetine, are secreted in breast milk.
      Furthermore, genetic polymorphism has not been documented for fluvoxamine
      metabolism, whereas slow and fast metabolisers of paroxetine, and fast
      metabolisers of fluoxetine have been identified. SSRIs have a better tolerability
      profile than tricyclic antidepressants, as indicated by lower mean rank scores
      for behavioural toxicity. Moreover, SSRIs are associated with a much lower
      incidence of fatal toxicity than tricyclics, and appear to be relatively safe in
      overdosage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378374
TI  - Review of fluvoxamine safety database.
AB  - A review of the safety and tolerability of fluvoxamine in worldwide marketing
      studies involving 24,624 patients, predominantly receiving fluvoxamine treatment
      in uncontrolled studies in depression, has been conducted. There was a marked
      preponderance of female patients and patients aged between 30 and 50 years. The
      majority of patients were treated for 6 weeks, with the most frequent modal total
      daily dose being 100mg. The greatest proportion of adverse experiences occurring,
      by COSTART body system, affected the digestive system (24.1%), the nervous system
      (23.7%), and the body as a whole (15.3%). The only adverse experience with an
      incidence greater than 10% was nausea (15.7%), with somnolence (6.9%) and
      asthenia (6.2%) as the next most frequent experiences. Notably, the rates of
      agitation and anxiety were only 1.4 and 1.3%, respectively. The incidences of
      adverse experiences increased with age, and were slightly higher in females than
      males. 15.1% of patients discontinued treatment prematurely as a result of
      adverse experiences, principally nausea, dizziness, vomiting, somnolence,
      abdominal pain, and headache. The overall incidence of serious adverse events
      associated with fluvoxamine treatment was 2.5%, and the incidence of overall
      suicidality, including suicidal ideation, overdose, and intentional overdose as
      well as attempted and completed acts of suicide, was remarkably low at 0.8%.

PMID- 1378373
TI  - The safety of antidepressants.
AB  - In this article, a distinction is proposed between safe and less safe
      antidepressants. The safety of 18 antidepressants is discussed in relation to 3
      principal issues: the safety of the drug in the event of an overdose; the
      seriousness of its side effects; and the existence of dangerous interactions. On
      the basis of present information, it can be said with reasonable confidence that
      fluoxetine, fluvoxamine and paroxetine are safe antidepressants, and with some
      reservation (mainly because of hypnosedation) the same can be said of mianserin
      and trazodone.

PMID- 1378375
TI  - Ictal spikes: a marker of specific hippocampal cell loss.
AB  - Spontaneous seizures recorded from mesial temporal depth electrodes in the human
      are commonly manifested by one of two onset patterns: a high frequency discharge
      or a periodic spike discharge morphologically similar but clearly distinguished
      from ongoing interictal activity. We categorized medial temporal lobe seizure
      onset for the presence of periodic ictal spikes at a frequency of less than 2 Hz
      lasting for more than 5 sec to investigate the relationship of this ictal pattern
      to anatomical changes in the resected temporal lobe tissue. Fifty-one patients
      had hippocampal depth electrode recordings of spontaneous seizures, subsequent
      hippocampal resection, and quantitative cell counts of hippocampal subfields.
      Thirty-two of these patients had ictal spikes lasting at least 5 sec in more than
      50% of their seizures. The presence of ictal spikes was significantly correlated
      with decreased cells in CA1 only (P = 0.015). The correlation of a common ictal
      pattern with focal cell loss in the hippocampus suggests that
      electrophysiological manifestations of seizures provide a clue to the underlying
      pathological substrate. Ictal spikes may be a cause or result of the cell loss.
      These observations should be correlated with independent investigations in humans
      and animal models that reflect the CA1 cell loss associated with temporal lobe
      epilepsy.

PMID- 1378376
TI  - Comparative coherence studies in healthy volunteers and Down's syndrome patients
      from childhood to adult age.
AB  - Within the scope of the Munich Pediatric Longitudinal Study, EEG coherence was
      studied in 212 Down's syndrome patients and 342 healthy controls aged from 6
      months up to 30 years. The digitalized EEG records were subjected to spectral
      analysis. Frequency band-related coherences were calculated to reveal age
      specific differences in the functional relationship between two brain areas in
      Down's syndrome patients and controls. The results show that in the "eyes-open"
      state the intra-hemispheric coherence in the alpha band was significantly lower
      (P less than 0.05) in the Down's syndrome patients than in the controls whereas
      that in the delta bands it was generally higher. The intra-hemispheric coherence
      in the "eyes-closed" state was generally higher in the Down's syndrome groups
      than in the controls; however, significant differences could be detected only in
      some age groups. The age-specific development of coherence in the inter
      hemispheric parieto-occipital region was almost identical in Down's syndrome
      children as in controls, both with open and closed eyes. The most distinct
      differences were found in the fronto-central inter-hemispheric coherence (P less
      than 0.01), while the coherence deficiencies in the Down's syndrome group became
      more prominent with increasing age from school age onwards. These
      electrophysiological results are compared with the results of neuropathological
      and neurophysiological studies of other authors. It can be suggested that there
      are correlations with a significantly small number of dendritic spines in Down's
      syndrome patients, which was determined in neuropathological examinations. A
      neuronal model of interpretation is presented which explains the increasing
      developmental deficit with age in Down's syndrome children.

PMID- 1378377
TI  - The topographical features of EEGs in patients with affective disorders.
AB  - EEG data were obtained in the basic state from 16 scalp sites of 44 patients with
      affective disorder, diagnosed by DSM-III criteria, and 44 normal controls. The
      EEG power spectra were computed and the t statistic significance probability
      mapping (SPM) was applied to visualize regions where the patient group showed
      differences in the EEG topogram from the controls. The results show: (1) left
      occipital predominance (P3, O1) of alpha activities in the patients with
      affective disorders, (2) decreased alpha activities in Fp2 and F8 areas in
      patients with major depression without melancholia, (3) decreased alpha
      activities in F7 area in patients with bipolar disorder, manic, and (4) increased
      beta 2 activity in F4 and C4 areas in patients with major depression with
      melancholia. These results suggest that inter-hemispheric and intra-hemispheric
      relationships may be disturbed in patients with affective disorder.

PMID- 1378379
TI  - The different patterns of the photoparoxysmal response--a genetic study.
AB  - In order to investigate the significance of different patterns of the
      photoparoxysmal response (PPR), an electroencephalographic family study on 135
      probands and 371 relatives was carried out. The PPR was subclassified in 4
      phenotypically different types. Considering all types of PPR, the incidence was
      equal in siblings of probands with epilepsy and in siblings of probands without
      epilepsy. Type 4 (generalized spikes and waves) occurred more often both in
      probands with epilepsy and their siblings than the respective controls. Thus, the
      coincidence of photosensitivity will appear as higher if only a PPR with
      generalized spikes and waves is considered to be indicative of photosensitivity.
      A striking age dependency of the phenotypical expression of the PPR was found.
      These findings suggest that the phenotypical expression of the PPR is age-related
      and modified by other factors predisposing to generalized epilepsy, the varied
      patterns of the PPR only representing different levels of expression of the same
      genetically determined trait. The importance of an adequate technique of
      intermittent light stimulation is discussed.

PMID- 1378378
TI  - Periodic activity in cerebral arousal mechanisms--the relationship to sleep and
      brain damage.
AB  - Periodic activity during light sleep is well recognised in many physiological
      systems, particularly respiration. In damaged brains this activity can become
      exaggerated. It involves the autonomic nervous system, the muscles, the
      cerebrospinal fluid (CSF) pressure, the cerebral blood flow and the
      electroencephalogram (EEG). It is related to the level of arousal. The EEGs of 52
      subjects were studied. In stage 0-1 sleep, periods of alpha activity alternated
      with periods of theta activity related to the level of arousal. The intervals
      between the alpha onsets were measured and the data pooled. There was a dominant
      interval of about 16 sec. It is suggested that this is a physiological cerebral
      rhythm involving the cortex and the brain-stem activating mechanisms, responsive
      to outside stimuli but essentially endogenous. It is related to the controls of
      the autonomic, motor, and some cerebral auto-regulatory mechanisms. It may be
      severely disturbed in brain damage.

PMID- 1378380
TI  - Late magnetic fields and positive evoked potentials following infrequent and
      unpredictable omissions of visual stimuli.
AB  - Randomized and infrequent omissions during presentation of a steady train of
      visual stimulation produced distinctive wave forms of both the magnetic fields
      and electrical potentials. Electrical potentials at Pz showed a positive peak in
      response to the omitted stimuli which occurred on the average 445 msec after the
      time when a stimulus was anticipated. Analyses of the magnetic wave forms
      indicated that at least two separate sources appear to be active coincident with
      the electrical positive peak. One source localized in the occipital lobes in the
      vicinity of the visual cortex while the other source was located in the medial
      aspects of the temporal lobe or even deeper in the lateral thalamus. Judging from
      the calculated direction of current flow it appeared that the deep source would
      contribute greater potentials in the frontal areas of the scalp while the source
      in the occipital area would contribute to more posterior placement of electrodes,
      especially at Pz.

PMID- 1378381
TI  - Contralateral effects of cerebello-pontine angle exposure on human auditory brain
      stem evoked potentials.
AB  - Auditory brain-stem evoked potentials (ABEPs) were recorded during surgical
      procedures which exposed the cerebello-pontine angle (CPA) in humans. Recordings
      made with the CPA contralateral to stimulus exposed were compared with those
      obtained with the skin sutured at the end of surgery. Single-channel as well as 3
      channel Lissajous' trajectory (3-CLT) analyses were used to evaluate the effect
      of the surgical exposure on ABEP. The results suggest that exposure of the CPA
      contralateral to the stimulated ear did not affect dipole equivalent orientation
      nor magnitude, but did affect timing of the recorded activity being more
      pronounced for segments 'd'-'e' (corresponding to waves IV-V) than for 'a'-'b'
      (waves I-II). The results imply that the effects of disrupting the volume
      conductor may have been overwhelmed by other effects, such as local temperature
      changes. These changes, although not associated with clinical sequella, should be
      accounted for when analyzing subtle quantitative changes involving surgical
      exposures.

PMID- 1378382
TI  - An electroencephalographic comparison of effects of propofol and methohexital.
AB  - Thirty-eight patients were randomly allocated to receive propofol 1 mg/kg (group
      A, N = 10), methohexital 0.7 mg/kg (group B, N = 9), propofol 2 mg/kg (group C, N
      = 10), methohexital 1.5 mg/kg (group D, N = 9). They were all male with a mean
      age of 65.8 years (range, 46-85) and a mean weight of 76.2 kg (range, 50-109).
      Patients received no premedication. All drugs were administered as a single i.v.
      bolus. After baseline EEG recordings were obtained, i.v. bolus doses were given
      and the recording continued until the patients became fully responsive to verbal
      commands. The EEGs were visually analyzed and classified into 4 phases: phase 0,
      the wake physiologic pattern; phase 1, initial changes after i.v. bolus doses;
      phase 2, state of deep anesthesia; and phase 3, stage of recovery. The main
      change during phase 1 was increase in the amplitude of the background rhythms.
      Phase 2 was characterized by theta and delta activity and burst suppression in
      some patients. During phase 3 beta activity was seen following methohexital.
      Propofol produced a much deeper level of anesthesia compared to methohexital. The
      stage of deep anesthesia was prolonged following propofol. The clinical and EEG
      recoveries were prolonged after induction doses of propofol. The quality of
      recovery, however, was far superior with propofol. Methohexital produces a "hang
      over" effect which delays full recovery.

PMID- 1378383
TI  - Measurement of interhemispheric time differences in generalised spike-and-wave.

PMID- 1378384
TI  - Comments on article by Biggins et al.

PMID- 1378385
TI  - Primary and secondary bilateral synchrony in epilepsy: differentiation by
      estimation of interhemispheric small time differences during short spike-wave
      activity.
AB  - Estimation of interhemispheric small time differences (TDs) during spike-wave
      bursts in the EEG by coherence and phase analysis is useful for differentiation
      between primary bilateral synchrony (PBS) and secondary bilateral synchrony (SBS)
      in epilepsy. Because the previous method via Fast Fourier Transform needed long
      bursts for reliable analysis, a method using a 2-dimensional autoregressive model
      was newly developed to enable estimation of TDs even in 1.2 sec bursts, and
      applied to 19 epileptic patients with apparently bilaterally synchronous spike
      wave bursts. At the onsets of bursts, estimated maximal TDs were 5.8 msec or less
      and inconsistent in leading hemispheres in 10 patients with a clinical diagnosis
      of idiopathic, cryptogenic or symptomatic generalized epilepsy indicating PBS,
      while the maximal TDs were 9.3-41.5 msec and consistent in leading in 7 patients
      with clinically symptomatic partial epilepsy and also in two with idiopathic and
      symptomatic generalized epilepsy suggesting SBS. Among 8 patients with bursts
      which suggested SBS and long enough for evaluation of intra-burst TD variation,
      TDs tended to disappear in the middle to end parts of the bursts in 5 cases, but
      not in the other 3, suggesting 2 different pathophysiological mechanisms in SBS.

PMID- 1378386
TI  - Monoclonal antibody (Mab) markers for subpopulations of rat tracheal epithelial
      (RTE) cells.
AB  - We sought monoclonal antibodies (Mabs) that would recognize distinct subsets of
      rat tracheal epithelial (RTE) cells. Mice were immunized with pronase-dissociated
      RTE cells and hybridomas whose supernatants immunocytochemically stained
      subpopulations of tracheal cells were selected. We report the immunohistochemical
      staining properties of the antibodies and give the results of preliminary
      biochemical characterization of the antigens. Four different types of antibodies
      were produced. Antibody RTE 1 stained most RTE cells. Three antibodies (RTE 2, 7,
      and 13) recognized a subpopulation of nonciliated cells, both columnar and basal
      cells. Antibody RTE 3 intensely labeled the surface of ciliated cells. Three
      antibodies reacted with granule components of secretory cells; antibodies RTE 9
      and 11 reacted with mucous-type secretory cells and antibody RTE 12 stained all
      tracheal surface secretory cells. As described in detail, some antibodies were
      RTE cell specific while others also reacted with cells and secretions in other
      organs; the antibodies did not cross react with guinea pig or rabbit tissues.
      Periodate sensitivity of the antigens suggested that some antibodies recognized
      carbohydrate moieties while others detected peptide epitopes. In some cases,
      Western blotting revealed the molecular weights of the antigens, but some
      antigens were denatured by sodium dodecyl sulfate (SDS) and heat treatment. These
      antibody probes provide a useful means to immunochemically study changes in cell
      type distribution and/or epitope expression during development, injury, and
      regeneration.

PMID- 1378387
TI  - Immobilized pH gradient isoelectric focusing and immunoblotting for
      investigations of anti-Borrelia burgdorferi IgG antibodies.
AB  - Anti-Borrelia burgdorferi immunoglobulin G (IgG) responses in cerebrospinal
      fluid, serum, and joint fluid from Lyme disease patients were investigated by
      immobilized pH gradient (IPG) isoelectric focusing (IEF) in pH 4-10 and pH 4-7
      gels. After focusing, the anti-B.-burgdorferi antibodies were blotted by affinity
      driven transfer to antigen-coated polyvinylidene difluoride membranes
      (immunoblot) and the IgG antibodies were immunoenzymatically stained. IPG-IEF
      gels gave an excellent resolution of IgG and the immunoblot proved advantageous
      for the detection of anti-B. burgdorferi IgG antibodies. These antibodies, as
      judged from the electromigration characteristics, were found to contain
      oligoclonal as well as polyclonal subpopulations. This latter group included IgG
      antibodies that were inadequately resolved when separated by conventional carrier
      ampholyte IEF.

PMID- 1378388
TI  - Reliable phenotyping of alpha-1-antitrypsin by hybrid isoelectric focusing in an
      ultranarrow immobilized pH gradient.
AB  - Genetically determined phenotypes of the highly polymorphic human alpha 1
      antitrypsin were examined by hybrid isoelectric focusing in a narrow immobilized
      pH gradient. The chosen pH range from 4.45 to 4.75 was useful for identification
      and classification of the common PI M subtypes and a number of PI variants in the
      microheterogeneous regions of m6, m7, and m8. A high degree of resolution and an
      improved sharpness of PI bands was achieved with this excellent technique. It
      allowed the distinction of a new PI M variant, which has been designated M8, or
      Mingolstadt, according to the PI nomenclature. The pI difference of this mutant
      to the slightly cathodically located subtype M3 is approximately 0.001 pH unit.
      In addition, some common as well as rare phenotypes are presented.

PMID- 1378389
TI  - Rapid and simple method for the identification of apolipoprotein E isomorphic
      phenotypes from whole serum.
AB  - For the identification of apolipoprotein E isomorphic phenotypes, fresh or thawed
      serum was analyzed without prior delipidation or other pretreatment. Using 5%
      polyacrylamide gels with a 40 mm interelectrode distance, the isoforms were
      separated by isoelectric focusing in immobilized pH gradients ranging from pH 5
      to 6.5, and transferred onto polyvinylidene difluoride membranes by contact
      blotting for 1 h. The apolipoprotein E isoforms were identified following
      immunostaining. The electrophoresis required less than 2 h and the entire
      procedure could be completed within 6 h.

PMID- 1378390
TI  - The aerolysin membrane channel is formed by heptamerization of the monomer.
AB  - The cytolytic toxin aerolysin has been found to form heptameric oligomers by SDS
      PAGE electrophoresis, STEM mass measurements of single oligomers and image
      analysis of two-dimensional membrane crystals. Two types of crystal, flat sheets
      and long regular tubes, have been obtained by reconstitution of purified protein
      and Escherichia coli phospholipids. A noise-filtered image of the best
      crystalline sheets reveals a structure with 7-fold symmetry containing a central
      strongly stain-excluding ring that encircles a dark stain-filled channel 17 A in
      diameter. The ring is surrounded by seven arms each made up of two unequal sized
      domains. By combining projected views and side-views, a simplified model of the
      aerolysin channel complex has been constructed. The relevance of this structure
      to the mode of action of aerolysin is discussed.

PMID- 1378391
TI  - Different types of K+ channel current are generated by different levels of a
      single mRNA.
AB  - A cloned human voltage-sensitive K+ channel HLK3 which is present in T
      lymphocytes and in the brain was expressed in Xenopus oocytes and after permanent
      transfection of a human B-lymphocyte cell line (IM9). Injections of low cRNA
      concentrations into Xenopus oocytes led to the expression of a transient K+
      current, with saturating current-voltage (I-V) relationship, which was abolished
      by repetitive stimulations due to a slow recovery from inactivation. This
      transient K+ channel current was fully inhibited by 10 nM charybdotoxin.
      Injection of high concentrations of the same RNA led to a non-inactivating K+
      current, with linear I-V curve, which did not undergo use-dependent inactivation
      and was hardly sensitive to 10 nM charybdotoxin. Intermediate behaviour due to
      changing proportions of these two types of K+ channel expression were observed at
      intermediate RNA concentrations. Transient and non-inactivating K+ currents were
      also observed by both whole-cell and single channel patch-clamp recording from
      HLK3 transfected IM9 cells. The main conductance of the channel in the two
      different modes (inactivating and charybdotoxin-sensitive or non-inactivating and
      charybdotoxin-resistant) is the same (12-14 pS). Destruction of the cytoskeletal
      elements with cytochalasin D, colchicine or botulinum C2 toxin in oocyte
      experiments prevented expression of the sustained mode of the K+ channel. The
      results suggest that the sustained mode obtained at high RNA concentrations
      corresponds to channel clustering involving cytoskeletal elements. This
      differential functional expression of K+ channels associated with different
      levels of mRNA appears as a new important factor to explain the biophysical and
      pharmacological diversity of voltage-sensitive K+ channels.

PMID- 1378392
TI  - Characterization of a Shaw-related potassium channel family in rat brain.
AB  - Previously, we characterized a Shaker-related family of voltage-gated potassium
      channels (RCK) in rat brain. Now, we describe a second family of voltage-gated
      potassium channels in the rat nervous system. This family is related to the
      Drosophila Shaw gene and has been dubbed Raw. In contrast to the RCK potassium
      channel family the Raw family utilizes extensive alternative splicing for
      expressing potassium channel subunits with variant C-termini. These alternative C
      termini do not appear to influence the electrophysiological and pharmacological
      properties as studied in the Xenopus oocyte expression system. In situ
      hybridizations to sections of rat brain indicate that members of the Raw family
      are expressed in distinct areas of the central nervous system. Probably, Raw
      channels are expressed predominantly as homomultimers. Immunocytochemical
      experiments with antibodies against Raw3 and RCK4 proteins which form two
      distinct A-type potassium channels indicate that in hippocampus the two channels
      are expressed both in different neurons and in the same ones. In general,
      properties of Raw potassium channels appeared to be similar to RCK channels.
      However, Raw outward currents, in contrast to RCK currents, exhibit an intense
      rectification at test potentials higher than +20 to +40 mV. RCK and Raw channel
      subunits did not measurably coassemble into RCK/Raw heteromultimers after
      coinjecting RCK and Raw cRNA into Xenopus oocytes. These results suggest that
      members of the RCK and the Raw potassium channel families express potassium
      channels which form independent outward current systems. Combining the results of
      in situ hybridizations, immunocytochemical staining and expression of the cloned
      potassium channels in Xenopus oocytes demonstrates that unrestrained mixing of
      potassium channel subunits to form hybrid channels does not occur in the rat
      central nervous system. A single neuron is able to express multiple,
      independently assembled potassium channels.

PMID- 1378394
TI  - Suppression of beta-1,3-glucanase transgene expression in homozygous plants.
AB  - A chimeric construct containing the Nicotiana plumbaginifolia beta-1,3-glucanase
      gn1 gene was introduced into Nicotiana tabacum SR1 to produce high levels of the
      enzyme constitutively. We determined that the GN1 protein represents a basic beta
      1,3-glucanase isoform which accumulates into the vacuoles of the transgenic
      plants. Analysis of the progeny of the transgenic plant with the highest levels
      of gn1 expression revealed an unexpected phenomenon of gene suppression. Plants
      hemizygous for the T-DNA locus contained high levels of gn1 mRNA and exhibited a
      14-fold higher beta-1,3-glucanase activity than untransformed plants. However,
      the expression of gn1 was completely suppressed in the homozygous plants: no
      corresponding mRNA or protein could be detected. This suppression mechanism
      occurs at a post-transcriptional level and is under developmental control. In
      addition, by generating haploid plants we found that this silencing phenomenon is
      not dependent on allelic interaction between T-DNA copies present at the same
      locus of homologous chromosomes, but rather is correlated with the transgene dose
      in the plant genome. We postulate that high doses of GN1 protein relative to the
      level(s) of other still unknown plant products could trigger the cellular
      processes directed to suppress gn1 expression.

PMID- 1378393
TI  - Regulation of CFTR expression and function during differentiation of intestinal
      epithelial cells.
AB  - CFTR, the protein defective in cystic fibrosis is regulated during
      differentiation of intestinal epithelial cells. The undifferentiated cells (Caco
      2 and HT-29) show a lower level of CFTR mRNA, while a 10-fold increase is seen in
      differentiated cells. These differences correlate well with those of other
      intestinal-specific genes, including sucrase-isomaltase, villin and alpha 1
      antitrypsin, indicating that the regulation is cell specific. In Caco-2 cells the
      increase in CFTR mRNA cannot be accounted for by increased transcription of the
      gene. These data indicate that CFTR mRNA stabilizing factor(s) might be present
      in differentiated cells. The higher levels of CFTR mRNA in differentiated cells
      are accompanied by decreased protein levels, indicating, as well, involvement of
      translational control in the regulation of CFTR in these cells. Finally, fully
      differentiated cells show lowered levels of cyclic AMP-activated C1- transport,
      the characteristic function of CFTR. Thus, CFTR function in differentiated cells
      is modulated by a complex interaction of regulatory elements. Caco-2 and HT-29
      cells provide a suitable in vitro system in which to study the mechanism of
      regulation of CFTR.

PMID- 1378395
TI  - DNA deformation in nucleoprotein complexes between RNA polymerase, cAMP receptor
      protein and the lac UV5 promoter probed by singlet oxygen.
AB  - Singlet oxygen (1O2), generated by exciting an eosin-Tris complex with a high
      intensity beam of radiation at 532 nm, was used to chemically modify bases in
      fragments of DNA containing the lac UV5 promoter in the presence of the DNA
      binding proteins, RNA polymerase and CRP (cAMP receptor protein). Subsequent
      treatment with piperidine selectively cleaved the DNA at specific modified bases
      in the sequence. Using this technique we show first that the reactivity of DNA
      bound by CRP differs in the presence and absence of RNA polymerase. Hence the
      local conformation of CRP-bound DNA must change during the transition to the open
      complex. However, no reactivity is observed at the sites of the 40 degrees kinks
      described in the cocrystal structure (Steitz, 1990). Secondly we show that there
      is unique CRP-dependent reactivity at a specific site (position -46 on the upper
      strand) in the open complex. Finally, in the open complex, 1O2 also reacts with
      sites 90 bp upstream from the transcription start point. This reactivity is
      qualitatively CRP-independent. We infer that 1O2 reacts at sites where the
      promoter DNA is significantly distorted, and suggest that the pattern observed
      reflects the functional orientation of an active transcriptional complex in which
      the DNA is bent to form an extended loop.

PMID- 1378396
TI  - The positive regulator CfaD overcomes the repression mediated by histone-like
      protein H-NS (H1) in the CFA/I fimbrial operon of Escherichia coli.
AB  - CFA/I fimbriae of enterotoxigenic Escherichia coli are expressed at 37 degrees C
      and not at 20 degrees C. Expression of CFA/I fimbriae requires two DNA regions
      (regions 1 and 2) which are separated by 40 kb on the wild type plasmid. Region 2
      encodes a protein (CfaD) which activates the promoter in region 1. We
      investigated whether the histone-like protein H-NS (H1) of E.coli is involved in
      the temperature regulated expression of CFA/I fimbriae. As demonstrated recently
      with other temperature regulated genes, a mutation in the gene coding for this
      nucleoid-associated H-NS (H1) protein resulted in derepression of CFA/I
      expression. CFA/I fimbriae were now expressed both at 20 degrees C and 37 degrees
      C. More strinkingly, the positive regulator CfaD was not needed for CFA/I
      expression in an H-NS- strain. This indicates that CfaD diminishes an inhibitory
      effect of the H-NS nucleoid-associated protein. We also showed that in the H-NS-
      strain the CfaD protein still has a positive effect on the transcription of
      CFA/I.

PMID- 1378397
TI  - Mutational analysis of a DEAD box RNA helicase: the mammalian translation
      initiation factor eIF-4A.
AB  - eIF-4A is a translation initiation factor that exhibits bidirectional RNA
      unwinding activity in vitro in the presence of another translation initiation
      factor, eIF-4B and ATP. This activity is thought to be responsible for the
      melting of secondary structure in the 5' untranslated region of eukaryotic mRNAs
      to facilitate ribosome binding. eIF-4A is a member of a fast growing family of
      proteins termed the DEAD family. These proteins are believed to be RNA helicases,
      based on the demonstrated in vitro RNA helicase activity of two members (eIF-4A
      and p68) and their homology in eight amino acid regions. Several related
      biochemical activities were attributed to eIF-4A: (i) ATP binding, (ii) RNA
      dependent ATPase and (iii) RNA helicase. To determine the contribution of the
      highly conserved regions to these activities, we performed site-directed
      mutagenesis. First we show that recombinant eIF-4A, together with recombinant eIF
      4B, exhibit RNA helicase activity in vitro. Mutations in the ATPase A motif
      (AXXXXGKT) affect ATP binding, whereas mutations in the predicted ATPase B motif
      (DEAD) affect ATP hydrolysis. We report here that the DEAD region couples the
      ATPase with the RNA helicase activity. Furthermore, two other regions, whose
      functions were unknown, have also been characterized. We report that the first
      residue in the HRIGRXXR region is involved in ATP hydrolysis and that the SAT
      region is essential for RNA unwinding. Our results suggest that the highly
      conserved regions in the DEAD box family are critical for RNA helicase activity.

PMID- 1378399
TI  - DNase-I hypersensitivity analysis of the L-type pyruvate kinase gene in rats and
      transgenic mice.
AB  - The rat L-type pyruvate kinase gene possesses two promoters located 500 bp apart.
      The L' promoter is specific to erythroid cells. The L promoter is specific to
      liver and is regulated by diet and hormones; positively by glucose and insulin
      and negatively by glucagon via cAMP. The DNA elements involved in this tissue
      specific and hormone-regulated gene expression are located within 3.2 kbp of 5'
      flanking region as previously demonstrated by transgenic mice analysis [Tremp, G.
      L., Boquet, D., Ripoche, M. A., Cognet, M., Yu-Chun, L., Jami, J., Kahn, A. and
      Daegelen, D. (1989) J. Biol. Chem. 264, 19,904-19,910]. Moreover, we have
      observed in these mice that gene expression was dependent on the transgene copy
      number and independent of the integration site. We present here DNase-I
      hypersensitivity analysis of the endogenous rat L-type pyruvate kinase gene and
      of two transgene constructs in relation to development, tissue differentiation,
      nutritional and hormonal status. In rats, two groups of proximal sites were
      detected on the endogenous gene; hypersensitive site (HSS) HSS-1 in adult liver
      and HSS-A in fetal liver (a major erythropoietic tissue). Both groups are
      probably related to the transcriptional initiation complexes at either the L or
      L' promoter. Two other distal groups were detected; HSS-2 at -3 kbp (with respect
      to the liver-specific cap site) in adult liver and HSS-B around -4 kbp in fetal
      liver. These sites are thought to correspond to activating sequences; in adult
      liver, deletion of a fragment encompassing HSS-2 provokes a dramatic reduction of
      transcription starting at the L promoter of the transgene. In adult liver, HSS-1
      appears to be a transcription-associated site, being greatly weakened in fasted
      rats, while HSS-2 is transcription independent. The pattern of DNase-I
      hypersensitivity is similar for the rat endogenous gene and for the complete rat
      transgene; the liver-specific HSS-1 and HSS-2 are present and the intensity of
      the sites is correlated to the number of integrated copies. Interestingly, HSS-1
      is still detectable and its intensity remains proportional to the number of
      integrated copies in a truncated transgene with HSS-2 deletion, while this
      transgene is very weakly (but nevertheless tissue-specifically) expressed. These
      results strongly suggest that each transgene copy possesses a complete set of
      specific nucleoprotein complexes and that, with or without HSS-2, the DNA is in a
      potentially active configuration.

PMID- 1378398
TI  - Replication control of plasmid R1: RepA synthesis is regulated by CopA RNA
      through inhibition of leader peptide translation.
AB  - The replication frequency of plasmid R1 is post-transcriptionally controlled by
      an antisense RNA, CopA, that binds to the leader region in the RepA mRNA, CopT,
      and ultimately inhibits the synthesis of the replication initiator protein RepA.
      We present results demonstrating that CopA controls RepA synthesis indirectly. A
      reading frame for a 24 amino acid leader peptide (Tap, translational activator
      peptide) is located in the region between the copA and repA genes. A
      translational fusion between the tap and lacZ genes was used to demonstrate that
      tap is translated and controlled by CopA. Stop codons (UAA, UAG and UGA)
      introduced at three different positions within the tap gene led to a severe
      decrease in repA expression. Specific suppression of the stop codons reversed the
      effect. This indicates that tap translation is required for RepA synthesis.
      Phylogenetic comparisons between IncFII-like plasmids, together with previous in
      vitro and in vivo results (Ohman and Wagner, 1989, 1991), suggest that a stable
      RNA stem-loop structure sequesters the repA ribosome binding site irrespective of
      CopA-CopT duplex formation. The results presented here show that ribosomes
      translating the tap reading frame have to terminate close to the start codon of
      repA to permit reinitiation (direct translational coupling), and that transient
      disruption of the inhibitory RNA stem-loop is insufficient for activation of repA
      translation. The possibility that direct translational coupling is required
      because of a suboptimal repA RBS cannot be excluded.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1378400
TI  - An improved procedure for reconstitution of the uncoupling protein and in-depth
      analysis of H+/OH- transport.
AB  - An improved procedure for reincorporation of isolated uncoupling protein (UCP)
      from brown adipose tissue into phospholipid vesicles is reported and H+ uptake in
      K(+)-driven exchange diffusion quantitatively analyzed. UCP is isolated and
      reconstituted with medium-length linear-chain alkyl polyoxyethylene. In the
      critical step of vesicle formation, the stepwise removal of the detergent by
      polystyrene beads is applied. Vesicles are generated in the presence of solutes
      and buffers to be internalized which are then removed by gel filtration. The
      internal volume is about 4 microliters/mg phospholipid with a vesicle diameter of
      100 nm. One vesicle contains, on average, six molecules UCP. The best results are
      obtained with purified egg yolk phosphatidylcholine. Addition of PtdEtn, PtdSer
      decreases the vesicle size and, still more, H(+)-transport activity by UCP.
      Asolectin completely inactivates UCP. K(+)-gradient-driven H+ uptake is 80%
      inhibited by external GTP and 95% by internal plus external GTP. When H+
      transport is recorded externally by a pH electrode and internally by pyranine,
      the kinetics show no delay resulting from intervening membrane-bound H+ pools.
      Total H+ uptake after addition of carbonylcyanine m-chlorophenylhydrazone (CCCP)
      and valinomycin corresponds to the diffusion between H+ and K+ and is unchanged
      by GTP. The linear correlation of H(+)-transport inhibition to GTP binding
      demonstrates that all UCP molecules incorporated are equally active. The exchange
      diffusion between H+ uptake and K+ efflux is demonstrated using a K+ electrode
      and 86Rb measurements. Recording delta psi using 3,3'
      diispropylthiadicarbocyanine shows a rapid generation of delta psi on valinomycin
      addition, which decreases only slightly with H+ uptake, even after addition of
      CCCP or gramicidin. The delta psi collapses only after addition of external K+.
      By demonstrating that valinomycin-induced K+ and H+ fluxes reflect relaxation
      into the diffusion equilibrium state, the transport rate of UCP can be evaluated
      as a first-order rate, VH+/CH+, in which the rate, VH+, is related to H(+)-uptake
      capacity, CH+. This allows quantitative comparison of transport rates
      independently of the variable CH+. The dependence on delta psi of H+ transport is
      measured by varying external K+ concentration. A virtually linear relation of the
      rate to the K(+)-diffusion potential is observed, although the capacity is only
      slightly changed. The linear VH+/delta psi relationship resembles an open-channel
      type of transport, but is discussed in terms of a low-activation-barrier type of
      carrier mechanism, in contrast to the log (VH+/delta psi) relation found for the
      ADP/ATP carrier with high activation barriers.

PMID- 1378401
TI  - The role of calcium and protein kinase C in the IgE-dependent activation of
      phosphatidylcholine-specific phospholipase D in a rat mast (RBL 2H3) cell line.
AB  - Our previous studies have suggested that phosphatidylcholine-specific
      phospholipase D (PtdCho-PLD) plays a role in IgE-dependent diacylglycerol
      production, protein kinase C activation and mediator release in the RBL 2H3 mast
      cell line. We have extended these studies to examine the mechanisms by which
      PtdCho-PLD may be regulated in these cells. RBL 2H3 cellular lipids were labeled
      with [14C]arachidonic acid or [3H]myristic acid, then PtdCho-PLD activity was
      monitored by the formation of radiolabeled phosphatidylethanol when ethanol was
      included in the incubation medium. Trinitrophenol-ovalbumin conjugate (10 ng/ml),
      when added to cells previously sensitized with anti-(trinitrophenelated mouse
      IgE) (0.5 microgram/ml), ionomycin (1 microM) and thapsigargin (0.1 microM),
      stimulated PtdCho-PLD activation and mediator release in cells incubated in
      buffer containing 1.8 mM calcium, but not in cells incubated in calcium-free,
      buffer. Phorbol 12-myristate 13-acetate (0.1 microM) activated PtdCho-PLD in both
      buffers, but on its own did not trigger mediator release. When intracellular
      calcium was chelated with 5,5'-dimethyl-1,2-bis(2- aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid, trinitrophenol-ovalbumin conjugate failed to activate PtdCho
      PLD and histamine release. Similarly, down-regulation of protein kinase C
      activity by long-term exposure to the phorbol ester (0.1 microM) and
      preincubation of the cells with protein kinase inhibitors resulted in the loss of
      the trinitrophenol-ovalbumin response on PtdCho-PLD activity and histamine
      release. Taken together, the above results suggest that IgE-dependent PtdCho-PLD
      activation is dependent on both activation of protein kinase C and a rise in the
      intracellular free calcium concentration.

PMID- 1378402
TI  - Differential regulation of the transcript levels of some nuclear-encoded and
      mitochondrial-encoded respiratory-chain components in response to growth
      activation.
AB  - Biogenesis of mammalian mitochondria requires the participation of both nuclear
      and mitochondrial genes. In order to study the expression and coordination of
      these two sets of genes, serum-deprived, quiescent NIH 3T3 cells were activated
      by serum addition. The steady-state levels of the transcripts for two growth
      response genes (the mitochondrial adenine-nucleotide translocator and non
      mitochondrial beta-actin), one nuclear-encoded respiratory-chain component (F1
      ATPase beta-subunit) and the mitochondrial-encoded subunit I of cytochrome
      oxidase decreased significantly in quiescent cells and were rapidly restored with
      similar kinetics after addition of serum. The transcripts for two additional
      nuclear-encoded mitochondrial genes (cytochrome c1 and cytochrome oxidase subunit
      IV) did not respond to serum deprivation or growth activation. These results
      imply that mitochondrial biogenesis is at least partially regulated through
      growth-dependent mechanisms. Furthermore, the expression of nuclear genes
      encoding mitochondrial respiratory-chain components does not appear to be tightly
      coordinated, suggesting the existence of multiple control circuits.

PMID- 1378403
TI  - Molecular cloning, stage-specific expression and cellular distribution of a
      putative protein kinase from Plasmodium falciparum.
AB  - A putative protein kinase gene (PfPK2) has been isolated from the human parasite
      Plasmodium falciparum by using a mixed oligonucleotide pool which corresponds to
      a highly conserved region of serine/threonine protein kinases. The complete
      nucleotide sequence of 5 kb suggests the existence of a second transcriptional
      unit besides that of the PfPK2 gene, separated by a highly (A+T)-rich region and
      transcribed in a different orientation. No intron sequence exists in PfPK2. The
      predicted amino acid sequence of PfPK2 contains features characteristic of
      eukaryotic serine/threonine protein kinases. Within its putative catalytic domain
      it shares 33%, 30%, and 28% amino acid identities with rat calcium-calmodulin
      dependent protein kinase, human protein kinase C, and bovine cAMP-dependent
      protein kinase, respectively. Outside the catalytic domain, however, PfPK2 has no
      homology with regulatory domains of other protein kinases, indicating PfPK2 might
      be modulated by signals different from those of higher eukaryotes or might be
      associated with other regulatory subunits. Using a specific antiserum raised in
      rabbits against a recombinant fragment of the protein expressed in Escherichia
      coli, PfPK2 was found to be expressed in a stage-specific fashion and mainly
      localized in the parasitic membrane.

PMID- 1378404
TI  - Functional analysis of primers and templates in the synthesis of DNA catalyzed by
      human immunodeficiency virus type 1 reverse transcriptase.
AB  - The kinetics of copying of poly(A).(dT)n, poly(A).(U)n, poly(dA).(dT)n and
      poly(A).(dT)9-U by reverse transcriptase of human immunodeficiency virus-1 (HIV
      1) has been studied and the binding affinity of the enzyme, for template or
      primer, determined. Short oligonucleotides and dTTP served as primers in the HIV
      1 reverse-transcriptase-dependent DNA synthesis. Km and Vmax were measured as
      functions of the primer chain length; the logarithm of the values of both Km and
      Vmax increased linearly up to 10. For longer primers (n = 11 to n = 24) the
      increase of those values changes very little. The enhanced affinity of the
      primers, (dT)n or (U)n due to the formation of one complementary pair, A.dT,
      dA.dT, A.U was estimated as a factor of 2. A specific property of HIV-1 reverse
      transcriptase compared with other DNA polymerases (procaryotes, eucaryotes, other
      retroviruses and archaebacteria) was its higher affinity to riboprimers as
      compared to deoxyriboprimers. Relative initial rates when copying poly(A) or
      poly(dA) templates using different primers and various conditions were compared;
      the optimal temperature for the reaction of polymerization with poly(A) or
      poly(dA) templates and (U)10, (dT)10 or (dT)9-U primers was determined. The
      maximal activity of the enzyme in the case of poly(A) and decanucleotide primers
      was found at temperatures between 27-31 degrees C. An increase in the primer
      length results in the stabilization of the template.primer duplex complexed to
      the enzyme, thus increasing to more than 40 degrees C the optimal temperature of
      polymerization. The activation energy (Ea) values of the polymerization reaction
      for different template.primer complexes were evaluated.

PMID- 1378405
TI  - Molecular and metabolic changes in white adipose tissue of the rat during
      development of ventromedial hypothalamic obesity.
AB  - We have previously shown that rats made obese by lesion of ventromedial
      hypothalamus (VMH) nuclei, demonstrate an hyper-responsiveness to insulin with
      regard to whole-body glucose utilization one week after injury. This is mainly
      due to an increased glucose uptake in white adipose tissue. Six weeks after the
      lesion, glucose utilization in white adipose tissue returns to normal values.
      These modifications in insulin responsiveness could be mediated by altered
      activity and/or concentration of intracellular insulin effectors. In this study,
      we have measured the expression of the insulin-sensitive glucose transporter,
      Glut 4 and the activities and expression of key lipogenic enzymes (fatty-acid
      synthase and acetyl-CoA carboxylase) in white adipose tissue, one and six weeks
      after the lesion. All these parameters, as well as glucose transport and
      metabolism determined in white adipocytes, were markedly increased one week after
      the lesion. They returned to control values within six weeks in VMH-lesioned
      rats. These results indicate the existence of an increased expression of Glut 4
      and lipogenic enzymes in white adipose tissue of VMH-lesioned rats which
      decreased with time and were parallel to glucose utilization determined in vivo.

PMID- 1378406
TI  - Aprotinin can inhibit the proteolytic activity of thrombin. A fluorescence and an
      enzymatic study.
AB  - Aprotinin has been shown to reduce blood loss and blood requirement when
      administered prior to surgery and this therapeutic benefit appears to be related
      to its specificity as a protease inhibitor. The inhibition of plasmin by
      aprotinin is well characterized, but little is known of its effect on thrombin.
      In preliminary experiments, we showed that aprotinin can prevent platelet
      aggregation induced by thrombin. Follow-up studies have now been performed in
      order to clarify the effect of aprotinin on thrombin. A fluorescence study of the
      direct binding of aprotinin to human alpha-thrombin was analysed according to the
      Michaelis-Menten model and a dissociation constant of 30 x 10(-6) mol.l-1 was
      determined. Aprotinin can displace p-aminobenzamidine, a fluorescent-probe
      molecule which binds to the active site of serine proteases, showing that the
      active site of thrombin was involved. Aprotinin also inhibited the ability of
      thrombin to induce a fibrin clot from purified fibrinogen and to induce the
      hydrolysis of the chromogenic substrate H-D-phenylalanylpipecolylarginine-p
      nitroanalidehydrochloride++ + (S-2238). With S-2238, double-reciprocal plots show
      that the inhibition is competitive with a Ki of 61 microM and a Km of 1.72
      microM. Aprotinin was a potent inhibitor of thrombin-induced aggregation. A
      Schild plot of the aggregation data yielded a slope of 0.97 +/- 0.12 and an
      apparent dissociation constant of 57.0 +/- 13.1 microM (mean +/- SEM). Thus, the
      inhibition of thrombin-induced platelet aggregation by aprotinin fits a model of
      competitive inhibition. Conclusions are that, in addition to a possible direct
      effect of aprotinin on platelets, the inhibition of thrombin-induced platelet
      activation by aprotinin can be also explained, in part, by a direct effect of the
      inhibitor on the thrombin molecule itself. This supports the concept that a
      proteolytic step is involved in the platelet response to thrombin. Finally,
      evidence is in favour of the participation of Trp245 in the fluorescence response
      of thrombin on binding to aprotinin.

PMID- 1378407
TI  - Prevalence of the primitive megakaryocyte progenitors (BFU-meg) in adult human
      peripheral blood.
AB  - The in vitro growth of early (megakaryocyte burst-forming units, BFU-meg) and
      late (megakaryocyte colony-forming units, CFU-meg) megakaryocyte (meg)
      progenitors has been evaluated in normal adult human peripheral blood (PB). All
      the experiments were carried out using CD34+ cells, which were assayed in a serum
      free fibrinclot assay. PB BFU-meg were morphologically characterized as
      plurifocal aggregates containing greater than 50 cells/colony, distinct from
      unifocal CFU-meg, in a limiting dilution assay. At variance with PB CFU-meg, PB
      BFU-meg were unaffected by the complement-mediated cytotoxicity with anti-HLA-DR.
      The optimal source of colony-stimulating activity for PB BFU-meg growth was
      recombinant human interleukin 3 (rhIL-3; 100 U/ml), which supported a
      significantly higher number of BFU-meg in comparison with recombinant human
      granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 200 U/ml, p = 0.043).
      Combinations of rhIL-3 (100 U/ml) plus rhGM-CSF (200 U/ml), rhIL-3 plus
      recombinant human interleukin 6 (rhIL-6; 100 U plus 100 U/ml) or rhIL-3 plus rhGM
      CSF plus rhIL-6 (100 U plus 200 U/ml plus 100 U/ml) failed to further increase
      the number of PB BFU-meg with respect to rhIL-3 (100 U/ml) alone. Both PB BFU-meg
      and CFU-meg were markedly inhibited, in a dose-dependent fashion, by increasing
      doses of human purified transforming growth factor-beta 1 (TGF-beta 1) (from
      0.001 to 10 ng/ml). Finally, the CFU-meg/BFU-meg ratio in PB (0.52) was
      significantly different from that of normal bone marrow (2.3), clearly indicating
      that adult human peripheral blood predominantly carries primitive megakaryocytic
      progenitors.

PMID- 1378409
TI  - Properties of Pseudomonas aeruginosa exotoxin A ionic channel incorporated in
      planar lipid bilayers.
AB  - Acidic conditions induce the incorporation of Pseudomonas aeruginosa exotoxin A
      into phospholipid planar bilayers and the formation of pores permeable to
      electrolytes. Channel openings occur as single events, although they may
      occasionally cluster in bursts. In 100 mM KCl, the elementary single channel
      current amplitude is 3.1 pA (at a transmembrane voltage of 100 mV), the mean open
      time is 1.3 ms, while bursts may last for several seconds. Noise analysis gave
      results identical to single channel analysis. Voltage pulse protocols and
      continuous cycling voltage ramps showed that the toxin channel is voltage
      dependent, having a higher probability of being open at positive voltages.

PMID- 1378408
TI  - In vivo and in vitro interaction between interleukin 6 and granulocyte colony
      stimulating factor in the regulation of murine hematopoiesis.
AB  - The interaction both in vitro and in vivo between human recombinant interleukin 6
      (IL-6) and human recombinant granulocyte colony-stimulating factor (G-CSF) in the
      regulation of mouse hematopoiesis was investigated. In the in vitro experiments,
      mouse bone marrow and spleen cells were cultured in semisolid medium containing 5
      or 50 ng/ml of G-CSF and concentrations ranging from 0 to 20 ng/ml of IL-6. In
      vivo, mice were treated for 4 days with 15, 50, or 250 micrograms/kg body
      weight/day of G-CSF, or with similar doses of G-CSF plus 50 micrograms/kg/day of
      IL-6, and the numbers of stem (spleen colony-forming units, CFU-S) and progenitor
      (megakaryocyte colony-forming cells, Meg-CFC; granulocyte-macrophage colony
      forming cells, GM-CFC) hematopoietic cells and mature circulating blood cells
      were evaluated. In vitro IL-6 caused dose-dependent suppression of the
      proliferation of GM-CFC, decreasing numbers of granulocyte-macrophage colonies in
      culture. The inhibitory effect of IL-6 decreased along with the increase of
      density of cultured cells, suggesting the influence of accessory, cytokine
      producing cells. In vivo, the numbers of GM-CFC and Meg-CFC in mice treated with
      IL-6 plus G-CSF were significantly closer to the values observed in untreated
      animals than those in mice treated with G-CSF only. The other cell populations
      were unaffected by IL-6 treatment. Our results demonstrate antagonism between IL
      6 and G-CSF in the in vitro stimulation of the proliferation of late granulocyte
      precursors, and they suggest a similar effect in the in vivo regulation of
      granulopoiesis and megakaryocytopoiesis at the progenitor cell level.

PMID- 1378410
TI  - Separation of gate- and channel-forming domains in the pore-forming protein of
      the outer membrane of Pseudomonas aeruginosa.
AB  - The domains of the pore-forming protein responsible for the gate and channel
      formations were separated and identified in the outer membrane of Pseudomonas
      aeruginosa. The proteolytic cleavage of the 46K channel protein, protein D2,
      yielded two major domains with apparent M(r) of 27K and 19K. We identified the
      27K polypeptide to be the channel-forming domain by an in vitro permeability
      assay. The channel size of purified 27K domain was indistinguishable from that of
      native protein D2. Degradation of the 19K domain into small subfragments
      increases the channel activity about ten times suggesting that the 19K
      polypeptide forms the gate or cap.

PMID- 1378411
TI  - Transforming growth factor beta has neurotrophic actions on sensory neurons in
      vitro and is synergistic with nerve growth factor.
AB  - Transforming growth factor beta (TGF beta) influences the growth and
      differentiation of a wide variety of nonneuronal cells (nnc) during embryogenesis
      and in response to wounding. In the present study TGF beta 1 and TGF beta 2 were
      examined for their neurotrophic actions on neonatal rat dorsal root ganglion
      (DRG) neurons with ganglionic nnc in dissociated cultures. TGF beta 1 and TGF
      beta 2 each increased both neuronal survival and levels of the peptide
      neurotransmitter substance P (SP) expressed per neuron as well as per culture.
      TGF beta 1 was maximally effective at a concentration of 40 pM, whereas TGF beta
      2 was about 10-fold less potent. Survival effects promoted by simultaneous
      treatment with both factors were not additive. TGF beta 1 also changed the
      morphology and distribution of DRG nnc which resulted in clustering of DRG
      neurons on top of the nnc. Cotreatment of the cultures with two different anti
      nerve growth factor (NGF) antibodies eliminated the neurotrophic effects of TGF
      beta 1. However, treatment with TGF beta 1 did not alter NGF mRNA expression in
      the cultures nor did it change the amount of NGF in the medium. Further, TGF beta
      1 greatly enhanced survival effects and SP stimulation promoted by exogenous NGF
      at concentrations up to 100 ng/ml. The neurotrophic effects of TGF beta 1 were
      significantly attenuated by decreasing the proportion of the ganglionic nnc,
      suggesting a role for these cells in mediating TGF beta 1 action on the neurons.
      It is hypothesized that the neurotrophic activity of TGF beta depended upon the
      presence of molecules immunologically related to NGF and that the effects of TGF
      beta were synergistic with NGF. These observations suggest that TGF beta may play
      a role in the differentiation and regeneration of DRG neurons in vivo.

PMID- 1378412
TI  - Identification and developmental expression of Src+ mRNAs in Xenopus laevis.
AB  - Alternative splicing of src mRNA has been demonstrated in several vertebrate
      species to yield a neuron-specific form of src protein termed pp60+. The function
      of pp60+ is unknown. The early developmental expression pattern of src+ RNA has
      not been previously examined. We have identified and characterized src+
      transcripts corresponding to the two src genes in Xenopus laevis using a reverse
      transcription/polymerase chain reaction (RT/PCR) method. Both Xenopus pp60+
      proteins have a 5-amino-acid insert in contrast to the 6-amino-acid insert in
      fish, birds, and mammals. Src+ mRNA first appears in neural plate stage Xenopus
      embryos, after neural induction signaling events but prior to neural
      differentiation. Analysis of dissected neural plate stage embryos showed that
      src+ mRNAs are localized to the neural plate. These findings suggest that pp60+
      may play a role in elaboration of neuron structure.

PMID- 1378413
TI  - A novel c-kit transcript, potentially encoding a truncated receptor, originates
      within a kit gene intron in mouse spermatids.
AB  - We have cloned a novel c-kit mRNA of 3.2 kb expressed in postmeiotic male germ
      cells. This transcript initiates in the genomic region immediately upstream of
      the exon coding for the second box of the split c-kit tyrosine kinase domain. The
      open reading frame (ORF) contains 12 novel amino acids in frame with the C
      terminal 190 amino acids of the c-kit protein. It lacks therefore the upstream
      region in the 5.5-kb c-kit mRNA encoding the extracellular and transmembrane
      domain, the ATP-binding site and the kinase insert domain present in the c-kit
      protein.

PMID- 1378414
TI  - Centrosome phosphorylation and the developmental expression of meiotic competence
      in mouse oocytes.
AB  - Previous studies suggested that the transition from an incompetent to a competent
      meiotic state during the course of oogenesis in the mouse involved a G2/M-like
      cell cycle transition (Wickramasinghe et al, 1991. Dev. Biol. 143, 162). The
      present studies tested the hypothesis that centrosome phosphorylation, an event
      normally induced by MPF, is required for this developmental transition and the
      expression of meiotic competence in cultured growing mouse oocytes. Multiple
      fluorescence labeling techniques were used to evaluate centrosome number,
      phosphorylation status, and microtubule nucleating capacity in competent and
      incompetent oocytes. Experimental conditions were established for reversibly
      altering the phosphorylation status of the centrosomes and the effects of these
      treatments on meiotic resumption were examined. Phosphorylated centrosomes
      nucleating short microtubules were observed in competent oocytes, whereas
      nonphosphorylated centrosomes and interphase microtubule arrays were found in
      incompetent oocytes. Upon recovery from nocodazole-induced microtubule
      depolymerization, short microtubules formed from centrosomes in competent
      oocytes, whereas long microtubules reappear in the cytoplasm of incompetent
      oocytes. Perturbation of the phosphorylation state of oocytes with activators of
      protein kinase A or protein kinase C resulted in the formation of long interphase
      microtubules in competent oocytes while centrosome phosphorylation was
      maintained. Treatment of competent oocytes with the phosphorylation inhibitor 6
      dimethylaminopurine also led to formation of long microtubules, although under
      these conditions centrosomes were dephosphorylated. When competent oocytes were
      treated simultaneously with puromycin and the phosphodiesterase inhibitor
      isobutyl methylxanthine (IBMX) for 6 hr, centrosomes became dephosphorylated;
      centrosomes were rephosphorylated when competent oocytes were further cultured in
      IBMX without puromycin. Conditions that induced centrosome dephosphorylation in
      competent oocytes resulted in the loss of the ability to express meiotic
      competence in culture, whereas maintenance of centrosome phosphorylation in these
      oocytes was correlated with the ability to resume meiosis. These results suggest
      that the G2/M transition that occurs when mouse oocytes progress from an
      incompetent to a competent state in vivo involves the phosphorylation of
      centrosomes and that the maintenance of centrosome phosphorylation is required
      for the in vitro expression of meiotic competence.

PMID- 1378415
TI  - Does nitric oxide mediate autoimmune destruction of beta-cells? Possible
      therapeutic interventions in IDDM.
AB  - Cytokines have been implicated as immunological effector molecules that induce
      dysfunction and destruction of the pancreatic beta-cell. The mechanisms of
      cytokine action on the beta-cell are unknown; however, nitric oxide, resulting
      from cytokine-induced expression of nitric oxide synthase, has been implicated as
      the cellular effector molecule mediating beta-cell dysfunction. Nitric oxide is a
      free radical that targets intracellular iron-containing enzymes, which results in
      the loss of their function. The cytokine IL-1 beta induces the formation of
      nitric oxide in isolated rat islets and the insulinoma cell line, Rin-m5F. NMMA
      and NAME, both inhibitors of nitric oxide synthase, completely protect islets
      from the deleterious effects of IL-1 beta. These inhibitors are competitive in
      nature and inhibit both the cytokine-inducible and constitutive isoforms of
      nitric oxide synthase with nearly identical kinetics. This may preclude their use
      as therapeutic agents because of increases in blood pressure which result from
      the inhibition of constitutive nitric oxide synthase activity. Aminoguanidine, an
      inhibitor of nonenzymatic glycosylation of cellular and extracellular
      constituents associated with diabetic complications, recently has been reported
      to inhibit nitric oxide synthase. Aminoguanidine is approximately 40-fold more
      effective in inhibiting the inducible isoform of nitric oxide synthase,
      suggesting that aminoguanidine or analogues may serve as potential therapeutic
      agents to block diseases associated with nitric oxide production by the inducible
      isoform of nitric oxide synthase. In vivo administration of TNF IL-1 has been
      shown to induce anti-diabetogenic effects in the NOD mouse. This anti
      diabetogenic effect of cytokines appears to conflict with evidence suggesting
      that cytokines mediate beta-cell dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378416
TI  - Chromosomal localisation of the mouse and human peripherin genes.
AB  - Using a mouse cDNA probe encoding for the major part of peripherin, a type III
      intermediate filament protein, we have assigned, by in situ hybridization, the
      mouse and human peripherin genes, Prph, to the E-F region of chromosome 15 and to
      the q12-q13 region of chromosome 12, respectively. These regions are known as
      homologous chromosomal segments containing other intermediate filament genes
      (keratins) and also other genes which could be co-ordinately regulated.

PMID- 1378417
TI  - Multiple amylase genes in Drosophila ananassae and related species.
AB  - The number and organization of amylase genes in Drosophila ananassae were
      investigated through classical genetic methods and in situ and filter
      hybridizations. At least four genes may be active in D. ananassae, organized as
      two independent pairs of closely linked copies on the 2L and 3L chromosomal arms.
      Several other species of the D. ananassae subgroup were studied and show the same
      chromosomal locations, suggesting an ancient duplication event. However, the
      number of Amy copies seems to be higher in the D. ananassae multigene family, and
      there is a striking intraspecific molecular differentiation.

PMID- 1378418
TI  - The Drosophila cellularization gene nullo produces a blastoderm-specific
      transcript whose levels respond to the nucleocytoplasmic ratio.
AB  - The initial development of the Drosophila embryo is characterized by rapid
      nuclear mitosis without cytokinesis. After 13 such mitoses, a coordinated cell
      division process called cellularization occurs, during which membranes
      simultaneously enclose each nucleus in a cell. Cellularization requires the
      establishment of a hexagonal network of actin and myosin filaments in the cortex
      of the embryo; the filaments are located on the cytoplasmic face of the
      invaginating membrane furrows. Zygotic expression of the nullo gene is essential
      for the maintenance of an intact actin-myosin network. We have cloned the nullo
      gene and present its sequence as well as a characterization of nullo transcript
      levels in wild-type and mutant embryos. The nullo gene encodes a predicted
      protein of 213 amino acids, a large proportion of which is basic. nullo
      transcripts are first detectable at nuclear cell cycle 11, peak in accumulation
      at the end of cycle 13, and disappear rapidly as cellularization begins. The gene
      does not appear to be expressed at any other time in the life of the organism.
      The normal accumulation of nullo transcripts does not require gene activity of
      other zygotic cellularization genes. The regulation of nullo RNA levels during
      cycle 14, however, is coupled to the nucleocytoplasmic ratio, which also controls
      the cessation of rapid, synchronous mitosis just before cellularization.

PMID- 1378419
TI  - The RNA polymerase II ternary complex cleaves the nascent transcript in a 3'---
      5' direction in the presence of elongation factor SII.
AB  - The process by which RNA polymerase II elongates RNA chains remains poorly
      understood. Elongation factor SII is known to be required to maximize readthrough
      at intrinsic termination sites in vitro. We found that SII has the additional and
      unanticipated property of facilitating transcript cleavage by the ternary
      complex. We first noticed that the addition of SII caused a shortening of
      transcripts generated by RNA polymerase II at intrinsic termination sites during
      transcription reactions in which a single NTP was limiting. Truncation of the
      nascent transcript was subsequently observed using a series of ternary complexes
      artificially paused after the synthesis of 15-, 18-, 20-, 21-, and 35-nucleotide
      transcripts. Transcripts as short as 9 or 10 nucleotides were generated in 5-min
      reactions. All of these shortened RNAs remained in active ternary complexes
      because they could be chased quantitatively. Continuation of the truncation
      reaction produced RNAs as short as 4 nucleotides; however, once cleavage had
      proceeded to within 8 or 9 bases of the 5' end, the resulting transcription
      complexes could not elongate the RNAs with NTP addition. Transcript cleavage
      requires a divalent cation, appears to proceed primarily in 2-nucleotide
      increments, and is inhibited by alpha-amanitin. The catalytic site of RNA
      polymerase II is repositioned after transcript cleavage such that polymerization
      resumes at the proper location on the template strand. The extent and kinetics of
      the transcript truncation reaction are affected by both the position at which RNA
      polymerase is halted and the sequence of the transcript.

PMID- 1378420
TI  - Hypoxia/reoxygenation stimulates endothelium to promote neutrophil adhesion.
AB  - An in vitro model was designed to study the role of ischemia/reperfusion and
      endothelium-derived oxygen free radicals on neutrophil adhesion, with particular
      interest in the endothelial adhesion molecules involved. Human umbilical vein
      endothelial cells were submitted to 5 h hypoxia followed by various times (20 min
      to 24 h) of reoxygenation. Human resting neutrophils were added to monolayers for
      the last 15 min of reoxygenation. Adherence was evaluated by myeloperoxidase
      assay. Under these conditions, we found an increased adhesion of neutrophils with
      two peaks after 20 min and 4 h reoxygenation. This was correlated with the
      respective expression of the preformed granule membrane protein 140 (GMP-140) and
      of the de novo synthesized endothelial leukocyte adhesion molecule 1 (ELAM-1) on
      endothelial surface. Superoxide dismutase and/or catalase, or oxypurinol added to
      cultures before hypoxia efficiently prevented neutrophil adhesion. These results
      underline the crucial role played by endothelial oxy radicals at reoxygenation in
      adhesion of leukocytes, which could lead to an amplification of the oxidative
      stress injury. The protection offered by free radical scavengers emphasizes the
      potential therapeutic use of antioxidants in postischemic vascular disorders.

PMID- 1378421
TI  - Regulation of human basophil activation. IV. Dissociation between cationic dye
      binding and histamine release: role of Ca2+ ions.
AB  - In previous studies we observed that in vitro histamine release from human
      basophils could be dissociated from the loss of affinity of basophil granules for
      a cationic dye, toluidine blue. In the present study we further explored the
      intracellular signals leading to the decrease in toluidine blue positive basophil
      (TB+) numbers, with or without histamine release. Since Ca2+ mobilization is a
      crucial event in secretion and particularly in histamine release, we studied the
      role of Ca2+ in histamine release as compared to TB+ decrease. In the presence of
      external Ca2+ (2 mM): i) Ca2+ channel antagonists verapamil and nifedipine up to
      10 microM were without effect on IgE-mediated histamine release and TB+ decrease;
      ii) loading of the leucocytes with Quin2 or preincubation with TMP-8, an internal
      Ca2+ antagonist, significantly inhibited the release of histamine and the
      decrease of TB+ basophils. In the absence of added external Ca2+:i) histamine
      release was abolished whereas the decrease of TB+ was not modified, even in the
      presence of EGTA;ii) the decrease of TB+ could be inhibited by prolonged EGTA
      preincubation, by Quin2 loading and incubation with TMB-8. We conclude that
      histamine release requires both external Ca2+ influx and mobilization of internal
      Ca2+. In contrast, no influx of external Ca2+ is required for TB+ decrease in
      which, however, internal Ca2+ mobilization appears to play an important role.

PMID- 1378422
TI  - Mouse monoclonal antibody to a latent epitope of leucocyte receptors for
      leukotriene B4.
AB  - Human blood polymorphonuclear (PMN) leucocytes and human leucocytes of the HL-60
      line, which were induced to differentiate by 1,25-dihydroxyvitamin D3, express
      stereospecific receptors for the potent chemotactic mediator, leukotriene B4
      (LTB4), that is derived by 5-lipoxygenation from arachidonic acid. Monoclonal
      antibodies to LTB4 receptors (LTB4-R) were generated by immunizing BALB/c mice
      with partially purified PMN leucocyte membrane proteins, and fusing their
      splenocytes with P3X63Ag8 mouse myeloma cells. Hybridoma supernatants were
      screened initially by binding to PMN leucocyte LTB4-R protein, which had been
      affinity cross-linked with aminopropylamide (APA)-LTB4 and immobilized in plastic
      wells through attachment of the linked APA-LTB4 to adherent Fab of monoclonal
      anti-LTB4. Of the three clones producing antibodies which bound to LTB4-R, 0.5
      mg/ml of one IgG3k antibody, termed E2, precipitated over 90% of the [3H]LTB4
      binding activity of solubilized PMN leucocyte membrane proteins. E2 also bound to
      a radiolabelled protein of 70,000-80,000 MW from 125I-labelled PMN leucocyte
      membranes [35S]-labelled HL-60 cell membranes, and PMN leucocyte membranes
      affinity-labelled with [3H]APA-LTB4, that was identical in size to the LTB4-R
      precipitated by the rabbit IgG anti-idiotypic antibodies. E2 did not bind to
      intact PMN leucocytes or modify the binding of [3H]LTB4 by PMN leucocytes. The
      binding of E2 to LTB4-R in purified membranes of PMN leucocytes was less than one
      fourth of that observed for the anti-idiotypic antibodies, but increased
      substantially after solubilization of the LTB4-R. The E2 monoclonal antibody thus
      recognizes a partially latent substituent of LTB4-R, which does not contribute to
      combining site function.

PMID- 1378423
TI  - Oligodendrocytes lack glycolipid anchored proteins which protect them against
      complement lysis. Restoration of resistance to lysis by incorporation of CD59.
AB  - Rat oligodendrocytes, which activate the classical pathway of complement in the
      absence of antibody, are highly sensitive in a reactive lysis assay using human
      C5b6 and EDTA serum. Oligodendrocytes may be relatively deficient in glycolipid
      linked complement regulatory protein(s), since digestion with
      phosphatidylinositol-specific phospholipase C (PI-PLC) failed to increase their
      sensitivity to serum, whereas complement-insensitive astrocytes, when treated
      with PI-PLC, became strikingly sensitive. To test the hypothesis that
      oligodendrocytes lack terminal complement regulatory molecule(s), human
      erythrocyte CD59, a recently described complement regulatory protein, was
      purified to homogeneity. The biological activity of the preparation was confirmed
      by reincorporating the protein into guinea-pig erythrocytes through its
      glycolipid anchor, which resulted in dose-dependent protection against human C5b6
      and EDTA serum. Incorporation of 10(5) molecules of human CD59 into rat
      oligodendrocytes resulted in good protection against homologous human complement
      (76%), and significant protection against rat complement homologous to the cell
      (36%). Protection could be reversed using an antibody to CD59.

PMID- 1378425
TI  - [Linear hyperpigmentation caused by bleomycin].
AB  - We report on an uncommon but characteristic cutaneous side-effect of bleomycin. A
      52-year-old woman being treated for carcinoma of the cervix developed linear
      hyperpigmentation in wheals in the lumbosacral region, the lateral thorax and
      above the elbow. The skin lesions appeared during the fourth cycle of
      chemotherapy with bleomycin. Histologically, incontinence of melanin, focal
      parakeratosis and a lymphocytic infiltrate with epidermotropism were prominent.
      By electron microscopic examination metabolically highly active melanocytes were
      found, with increased number of melanosomes at all stages of maturation and
      deposits of extracellular melanin in the underlying dermis. The epidermal
      keratinocytes were unchanged.

PMID- 1378424
TI  - Rapid visual assay of cytotoxic T-cell specificity utilizing synthetic peptide
      induced T-cell-T-cell killing.
AB  - Synthetic peptides are widely used to define the specificity of CD8+ cytotoxic T
      lymphocyte (CTL) clones. When many peptides need to be tested by the standard
      chromium release assay large numbers of a CTL clone are required. Specific
      synthetic peptide epitopes induce CTL clones to kill each other. This phenomenon
      can be directly visualized using an inverted microscope and forms the basis for a
      convenient assay, which can be performed with as few as 100 CTL per peptide and
      does not require radiolabelled targets.

PMID- 1378426
TI  - In vivo binding and autoradiographic imaging of (+)-3-[125I]Iodo-MK-801 to the
      NMDA receptor-channel complex in rat brain.
AB  - Radioiodinated (+)-3-Iodo-MK-801 is a high affinity radioligand for the N-methyl
      D-aspartate (NMDA) receptor-channel complex. We have demonstrated in vivo
      localization in the CNS of rat which is stereoselective and blocked by
      coinjection of unlabeled MK-801. Autoradiography indicates localization in vivo
      which is in concordance with in vitro autoradiographic studies. These results
      indicate that radioiodinated (+)-3-Iodo-MK-801 is a useful probe for in vitro and
      in vivo autoradiographic studies and suggest that radioligands for the NMDA
      receptor may be developed which will provide in vivo images of receptor
      distribution in man.

PMID- 1378427
TI  - Electrocardiographic changes following electroconvulsive therapy.

PMID- 1378428
TI  - Structural analysis of the O-antigen side chain polysaccharides in the
      lipopolysaccharides of Klebsiella serotypes O2(2a), O2(2a,2b), and O2(2a,2c).
AB  - The lipopolysaccharide (LPS) of Klebsiella serotype O2 is antigenically
      heterogeneous; some strains express multiple antigenic factors. To study this
      heterogeneity, we determined the structure of the O-antigen polysaccharides in
      isolates belonging to serotypes O2(2a), O2(2a,2b), and O2(2a,2c), by using
      composition analysis, methylation analysis, and both 1H and 13C nuclear magnetic
      resonance spectroscopy. The repeating unit structure of the 2a polysaccharide was
      identified as the disaccharide [----3)-beta-D-Galf-(1----3)-alpha-D-Galp-(1----]
      and was identical to D-galactan I, one of two O polysaccharides present in the
      LPS of Klebsiella pneumoniae serotype O1 (C. Whitfield, J. C. Richards, M. B.
      Perry, B. R. Clarke, and L. L. MacLean, J. Bacteriol. 173:1420-1431, 1991). LPS
      from serotype O2(2a,2b) also contained D-galactan I as the only O polysaccharide,
      suggesting that the 2b antigen is not an O antigen. The LPS of serotype O2(2a,2c)
      contained a mixture of two structurally distinct O polysaccharides and provides a
      second example of this phenomenon in Klebsiella spp. One polymer was identical to
      D-galactan I, and the other polysaccharide, the 2c antigen, was a polymer with a
      disaccharide repeating unit structure, [----3)-beta-D-GlcpNAc-(1----5)-beta-D
      Galf-(1----]. The 2c structure does not resemble previously reported O
      polysaccharides from Klebsiella spp. Periodate oxidation confirmed that D
      galactan I and the 2c polysaccharide are distinct glycans, rather than
      representing domains within a single polysaccharide chain. Monoclonal antibodies
      against the 2c antigen indicated that only LPS molecules with the longest O
      polysaccharide chains contained the 2c epitope.

PMID- 1378429
TI  - Analysis of the Pseudomonas aeruginosa major outer membrane protein OprF by use
      of truncated OprF derivatives and monoclonal antibodies.
AB  - TnphoA mutagenesis of the cloned oprF gene was utilized to generate 16 classes of
      fusions encoding differing lengths of the amino terminus of OprF fused to either
      alkaline phosphatase or to peptide tags of 1 to 20 amino acids, depending on the
      orientation and reading frame into which TnphoA was inserted. Representatives of
      each of the 16 classes were sequenced to determine the precise fusion joint. Four
      of these 16 representatives which produced in-frame fusions to alkaline
      phosphatase and another 8 with fusion joints in the amino-terminal half of OprF
      failed to react with a panel of 10 specific monoclonal antibodies. In contrast,
      OprF derivatives with predicted fusion joints at amino acids 180, 204, 289, and
      299 reacted with one to five of the monoclonal antibodies. Four other
      immunoreactive OprF derivatives were created by subcloning and encoded amino
      acids 1 to 187, 188 to 326, 1 to 273 and 1 to 170 plus 301 to 326. On the basis
      of reactivity with the TnphoA-truncated derivatives and subclones of oprF, the
      epitopes for all 10 monoclonal antibodies were localized, in part, to specific
      regions of OprF. Nine of the 10 monoclonal antibodies, 8 of which recognize
      surface-exposed epitopes, mapped within the carboxy-terminal region of OprF that
      is homologous to the Escherichia coli outer membrane protein OmpA. Thus, we
      concluded that parts of the carboxy terminus of OprF are exposed on the external
      face of the outer membrane. In addition, a clone containing only the first two
      cysteine residues of OprF demonstrated reactivity with monoclonal antibodies MA4
      4 and MA7-8 that was destroyed by 2-mercaptoethanol treatment, as was reactivity
      with intact OprF. Thus, we conclude that this first pair of cysteines at residues
      176 and 185 of mature OprF form a disulfide bond.

PMID- 1378430
TI  - Identification of formate dehydrogenase-specific mRNA species and nucleotide
      sequence of the fdhC gene of Methanobacterium formicicum.
AB  - The overlapping fdhA and fdhB genes of Methanobacterium formicicum, which encode
      the alpha and beta subunits, respectively, of formate dehydrogenase, were
      cotranscribed as part of an approximately 4.5-kb transcript. An additional gene
      (fdhC) upstream of fdhA was cotranscribed with fdhA and fdhB. The deduced amino
      acid sequence suggested that fdhC has the potential to encode a hydrophobic
      polypeptide with a calculated molecular weight of 29,417. A hydropathy plot of
      the hypothetical polypeptide indicated several potential membrane-spanning
      regions. The putative fdhC gene product had 28% identity with the deduced amino
      acid sequence of the nirC gene from Salmonella typhimurium. Northern (RNA) blot
      analyses and primer extension assays located a transcription start site 268 bp
      upstream of the initiation codon of fdhC. A sequence identical to the consensus
      promoter sequence for methanogenic organisms was situated between -35 and -25 bp
      from the proposed transcription start site. In addition to the 4.5-kb transcript,
      Northern blot analyses detected a 1.1-kb transcript with an fdhC-specific probe
      and a 3.4-kb transcript with either an fdhA- or fdhB-specific probe. The levels
      of all three transcripts were significantly greater in cells grown in media
      supplemented with molybdate.

PMID- 1378431
TI  - Cell-free synthesis of the branched RNA-linked msDNA from retron-Ec67 of
      Escherichia coli.
AB  - msDNA-Ec67 is produced in a clinical strain of Escherichia coli and composed of a
      67-base single-stranded DNA, which is linked to the 2'-OH group of the 15th rG
      residue of a 58-base RNA molecule by a 2',5'-phosphodiester linkage (Lampson, B.
      C., Sun, J., Hsu, M.-Y., Vallejo-Ramirez, J., Inouye, S., and Inouye, M. (1989)
      Science 243, 1033-1038). The production of msDNA-Ec67 is dependent upon retron
      Ec67, which consists of the msr-msd region and the gene for reverse transcriptase
      (RT). These two elements were separately cloned into plasmids; p67-BHO.6
      contained the msr-msd region and pRT-67 contained the RT gene under the lpp-lac
      promoter-operator. msDNA-Ec67 was produced only when cells were transformed with
      both plasmids. In addition, msDNA-Ec67 was synthesized in a cell-free system
      using total RNA prepared from cells harboring plasmid p67-BHO.6 and purified Ec67
      RT. Using this cell-free system, the priming reaction, during initiation of DNA
      synthesis, was demonstrated to be a specific template-directed event; only dTTP
      was incorporated into a 132-base precursor RNA yielding a 133-base compound. This
      specific dT addition could be altered to dA or dC by simply substituting the
      118th A residue of the putative msr-msd transcript with a T or G residue. The
      priming reaction was blocked when A was substituted for G at the 15th residue of
      the precursor RNA transcript, which corresponds to the branched rG residue in
      msDNA. DNA chain elongation could be terminated by adding ddNTP in the cell-free
      system, forming a sequence ladder. The DNA sequence determined from this ladder
      completely agreed with the msDNA sequence. The RT extension reaction was
      completely blocked when the RNA preparation was treated with RNase A but not when
      the preparation was treated with DNase. This clearly demonstrates that RNA but
      not DNA is responsible for the msDNA production. A part of the fully extended
      cell-free product contained a 13-base RNA strand resistant to RNase A, which is
      consistent with the previously proposed model. In this model, the 5'-end sequence
      of the msr-msd transcript (a2; bases 1-13) forms a duplex with the 3'-end
      sequence (a1) of the same transcript, thus serving as a primer, as well as a
      template for msDNA synthesis by RT. Our results are inconsistent with a model
      recently proposed by Lease and Yee (Lease, R. A., and Yee, T. (1991) J. Biol.
      Chem. 266, 14497-14503).

PMID- 1378432
TI  - Studies of the N-terminal half of human lactoferrin produced from the cloned cDNA
      demonstrate that interlobe interactions modulate iron release.
AB  - The factors influencing iron binding and release by lactoferrin have been
      addressed by comparison of the native full length molecule (Lf) with the N
      terminal half of human lactoferrin (LfN) produced from the cloned cDNA expressed
      in baby hamster kidney (BHK) cells. The coding sequences for LfN were inserted
      into the expression vector pNUT between the metallothionein promoter and the
      human growth hormone transcription termination sequences. Transformed BHK cells
      were grown in roller bottles where concentrations of LfN as high as 35 mg/liter
      were obtained. The pure protein, produced by the transformed BHK cells, was
      characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      protein blotting and immunodetection, N-terminal sequence analysis, UV-visible
      spectroscopy, electron spin resonance spectroscopy, and measurements of metal
      binding and release. By these criteria LfN was found to be correctly processed,
      glycosylated, and able to bind iron reversibly. Both UV-visible and electron spin
      resonance spectra of the half molecule were very similar to those of native
      lactoferrin and the full length lactoferrin produced in BHK cells, but there were
      marked differences in the pH at which iron release occurred. Iron release from
      LfN occurs in the pH range 6.0-4.0, compared with 4.0-2.5 for native lactoferrin
      and 6.2-4.0 for transferrin. These results suggest that the more facile release
      of iron from LfN compared with native lactoferrin results from the absence of
      stabilizing contacts between the N- and C-terminal halves and that the
      characteristic difference in pH stability between lactoferrins and transferrins
      is due primarily to differences in these interactions.

PMID- 1378433
TI  - The effects of cysteine mutations on the catalytic activities of the reverse
      transcriptase of human immunodeficiency virus type-1.
AB  - The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1)
      has only 2 cysteine residues at positions 38 and 280. In order to investigate the
      role of these cysteines in the structure and function of the enzyme, we have
      previously modified each of the cysteines to serines employing site-directed
      mutagenesis. Two of the mutant forms of HIV-1 RT, the single mutant of cysteine
      280 and a double mutant with both cysteines modified, were purified. In the
      present study we have compared the catalytic properties of the DNA-polymerizing
      and the ribonuclease H (RNase H) functions of the two mutant RTs to those of the
      native enzyme. The results indicate that the single mutant RT closely resembles
      the wild type enzyme in almost all the catalytic functions tested. The double
      cysteine mutant RT, on the other hand, exhibits several unique features. First,
      the specific activities of the RNA- and DNA-directed DNA synthesis are
      significantly lower than the corresponding activities of the other two enzymes.
      This probably results from the lower Vmax values exhibited by the double mutant
      RT, since the Km values calculated for all enzymes were similar. Second, the most
      outstanding differences are associated with the RNase H activity of the double
      mutant RT. The specific activity of RNase H is about 4-fold higher than the wild
      type and the single mutant RTs. Furthermore, the heat stability of the RNase H
      function of the double mutated RT is at least 15-fold higher than that of the
      other two RTs. The substantial resistance to heat denaturation is apparent only
      for the RNase H activity, since the DNA polymerizing function of the double
      mutant RT is as sensitive to heat denaturation as the other two proteins.

PMID- 1378434
TI  - In vitro expression of thyroxine-binding globulin (TBG) variants. Impaired
      secretion of TBGPRO-227 but not TBGPRO-113.
AB  - Thyroxine-binding globulin (TBG) is a glycoprotein that transports thyroid
      hormones in blood. Of two naturally occurring variants in man that harbor single
      proline substitutions (TBG-CD5 and TBG-Montreal), only TBG-CD5 manifests as
      complete TBG deficiency. In order to determine the pathophysiology of these TBG
      disorders, we expressed TBG-CD5 and TBG-Montreal (TBG-M), as well as the common
      type TBG (TBG-C) in reticulocyte lysate and Xenopus oocytes. Vectors encoding the
      three TBG types were constructed, transcribed in vitro, and their products of
      cell-free translation and processing by canine microsomal membranes were
      analyzed. TBG-C and TBG-M had identical mobility on denaturing polyacrylamide gel
      electrophoresis but could be distinguished by differences in thyroxine (T4)
      binding. TBG-CD5 had altered electrophoretic mobility and did not bind T4. TBG-C
      and TBG-M expressed in microinjected Xenopus oocytes showed properties similar to
      their respective serum forms, whereas TBG-CD5 was found in small amounts only
      intracellularly. Our results confirm that the previously described alanine 113 to
      proline substitution is responsible for the altered properties of TBG-M. The
      substitution of leucine 227 by proline in TBG-CD5 appears to impair its
      cotranslational processing and secretion.

PMID- 1378435
TI  - The expression of 80K/MARCKS, a major substrate of protein kinase C (PKC), is
      down-regulated through both PKC-dependent and -independent pathways. Effects of
      bombesin, platelet-derived growth factor, and cAMP.
AB  - We have examined the regulation of expression of 80K/MARCKS, a major and specific
      protein kinase C (PKC) substrate of Swiss 3T3 fibroblasts. Addition of bombesin
      (10 nM) to confluent quiescent cultures of these cells induced a dramatic and
      sustained down-regulation of 80-kDa mRNA and protein levels to a minimum of 5% of
      control within 8 and 48 h, respectively, without depletion of PKC activity. In
      contrast, the effect of phorbol 12,13-dibutyrate on 80K/MARCKS mRNA levels was
      transient, and recovery of these transcripts correlated with the loss of PKC
      activity. The ability of bombesin to down-regulate 80K/MARCKS mRNA levels was
      dose-dependent (ED50 0.5 nM) and was abolished by both the specific bombesin
      antagonist [Leu13 psi (CH2NH),Leu14]bombesin and by prior depletion of PKC. Of a
      range of agents tested, platelet-derived growth factor (PDGF), but not insulin or
      Ca2+ ionophore, also down-regulated 80K/MARCKS mRNA to 24% of control within 5 h.
      Prior down-regulation of PKC abolished the effect of PDGF at a concentration of 7
      ng/ml. Surprisingly, at higher doses (25 ng/ml), PDGF induced the down-regulation
      of 80K/MARCKS mRNA in a PKC-independent manner. Furthermore, elevation of cAMP,
      either through receptor-mediated mechanisms (e.g. prostaglandin E1) or by direct
      stimulation of adenylate cyclase (e.g. forskolin), also caused a marked dose
      dependent depletion of 80K/MARCKS mRNA levels, which were further reduced by co
      administration with cAMP-phosphodiesterase inhibitors. The rate of transcription
      of the 80K/MARCKS gene was unaltered by treatment of cells with either bombesin,
      PDGF, or forskolin/1-methyl-3-isobutylxanthine. These results indicate a role for
      both PKC-dependent and -independent pathways in growth factor-induced down
      regulation of 80K/MARCKS expression, through a post-transcriptional mechanism.

PMID- 1378436
TI  - Developmental control and alternative splicing of the placentally expressed
      transcripts from the human growth hormone gene cluster.
AB  - Four of the five genes in the human growth hormone gene cluster are expressed in
      the villous layer of the placenta. We report that the expression of these genes,
      hCS-A, hCS-B, hCS-L, and hGH-V, are coordinately induced during fetal
      development, increasing between 12 and 20 weeks of gestation and then plateauing
      through term. Within the context of this coordinate activation, these genes are
      expressed at widely different levels and are alternatively spliced in different
      patterns. There is a developmentally regulated switch in the relative expression
      of the two chorionic somatomammotropin genes, hCS-A and hCS-B. Starting from
      approximately equal levels at 8 weeks of gestation, hCS-A is expressed 5-fold
      more abundantly than hCS-B by term. The proportion of alternatively spliced hGH-V
      transcripts that retain intron 4 is also developmentally regulated, increasing 3
      fold during gestation to 15% at term. A small percentage of hCS transcripts
      stably retain intron 4 through gestation, the majority derived from the hCS-A
      gene. hCS-L transcripts undergo two distinct, developmentally stable, splicing
      pathways between exons 2 and 3. These result from the absence of the normal
      splice-donor site in intron 2 and the activation of two cryptic splice-acceptor
      sites. Despite high levels of sequence identity, the four placentally expressed
      genes in the growth hormone cluster generate a complex set of mRNAs based on
      alternative splicing and developmental regulation during gestation.

PMID- 1378437
TI  - Purification and characterization of heterodimeric human immunodeficiency virus
      type 1 (HIV-1) reverse transcriptase produced by in vitro processing of p66 with
      recombinant HIV-1 protease.
AB  - Active recombinant reverse transcriptase (RT) of human immunodeficiency virus
      type 1 (HIV-1) with an amino-terminal extension containing a hexa-histidine
      sequence has been prepared in milligram quantities in a pure heterodimeric
      (p66/p51) form by coordinated applications of immobilized metal affinity
      chromatography (IMAC) and HIV-1 protease treatment. The precursor protein,
      isolated from extracts of recombinant Escherichia coli by IMAC in a predominantly
      unprocessed form (p66), migrated on sodium dodecyl sulfate-polyacrylamide gels as
      a 66-kDa band with minor heterogeneity at lower relative molecular mass.
      Incubation of this protein with recombinant HIV-1 protease produced a stable
      heterodimeric RT that was purified in a single step by IMAC. The purified protein
      retained both RT and RNase H activity, and kinetic parameters (Km and Vmax) were
      measured with both RNA-dependent DNA polymerization and RNase H activity assays.
      Carboxyl-terminal sequencing of purified heterodimeric RT indicated that one
      subunit is intact p66, whereas the other, p51, is a truncated form of p66 that
      terminates at residue Phe440. Analysis of the HIV-1 protease digest revealed two
      cleavage sites, at Tyr483-Leu484 and Tyr532-Leu533, in addition to the site at
      Phe440-Tyr441 that is cleaved to produce p51.

PMID- 1378438
TI  - Characterization and regulation of the 58,000-dalton cellular inhibitor of the
      interferon-induced, dsRNA-activated protein kinase.
AB  - The P68 protein kinase is a serine/threonine kinase induced by interferon
      treatment and activated by double-stranded RNAs (dsRNAs). Once activated, the
      kinase phosphorylates its natural substrate, the alpha subunit of eukaryotic
      initiation factor 2 (eIF-2) leading to potential limitations in functional eIF-2
      and decreases in protein synthesis initiation. We have recently purified from
      influenza virus-infected cells a P68 kinase inhibitor, found to be a 58-kDa
      cellular protein. We have now investigated the mechanisms by which the 58-kDa
      inhibitor regulates P68 kinase activity and how the inhibitor itself is
      controlled. The 58-kDa inhibitor did not function by degrading or sequestering
      the dsRNA activator of P68 but could repress phosphorylation of eIF-2 alpha by an
      already activated protein kinase. Utilizing antibody prepared against a 58-kDa
      specific peptide, we showed that the 58-kDa proteins from infected and uninfected
      cells were present in equivalent amounts. Although kinase inhibitory activity
      could not be detected in crude uninfected cell extracts, ammonium sulfate
      treatment unmasked this activity and allowed purification of the cellular
      inhibitor with identical chromatographic properties as that from influenza virus
      infected cells. Finally, we have identified and partially purified a specific
      inhibitor of the 58-kDa protein which we refer to as an "anti-inhibitor." Based
      on these data, we present a model depicting the complex regulation of the
      interferon-induced protein kinase in eukaryotic cells.

PMID- 1378439
TI  - Use of expression mutants and monoclonal antibodies to map the erythrocyte Ca2+
      pump.
AB  - Deletion and truncation mutants of the human erythrocyte Ca2+ pump (hPMCA4b) were
      expressed in COS-1 cells. The reactivity patterns of these mutants with seven
      monoclonal antibodies were examined. Of the seven, six (JA9, JA3, 1G4, 4A4, 3E10
      and 5F10) react from the cytoplasmic side. JA9 and JA3 reacted near the NH2
      terminus and the COOH terminus of the molecule, respectively. 5F10 and 3E10
      recognized portions of the large hydrophilic region in the middle of the protein.
      The epitopes of 1G4 and 4A4 were discontinuous and included residues from the
      long hydrophilic domain and residues between the proposed transmembrane domains
      M2 and M3. Antibody 1B10, which reacts from the extracellular side, recognized
      the COOH-terminal half of the molecule. These results show that the NH2 terminus,
      the COOH terminus, the region between M2 and M3, and the large hydrophilic region
      are all on the cytoplasmic side. This means that there are an even number of
      membrane crossings in both the NH2-terminal and the COOH-terminal halves. Between
      residues 75 and 300 there must be at least two membrane crossings, and there are
      at least two membrane crossings in the COOH-terminal half of the molecule.

PMID- 1378440
TI  - Formation of a template committed complex on the promoter of a gene for the U6
      small nuclear RNA from the human requires multiple sequence elements, including
      the distal region.
AB  - Vertebrate U6 small nuclear RNA (snRNA) loci exemplify a novel class of
      polymerase III-transcribed genes that lack an intragenic control region (ICR).
      Instead important transcriptional control elements are located in the 5'-flanking
      region and resemble those found in promoters and enhancers of polymerase II
      transcribed genes. These include a proximal sequence element (PSE), a TATA
      element, and a distal region containing, at least, an octamer motif. We have used
      Sarkosyl to characterize steps in U6 promoter transcription in vitro in an
      unfractionated S100 extract and find very similar properties to those of the
      adenovirus VA1 gene that contains an ICR. Preformed preinitiation complexes are
      stable to 0.015% Sarkosyl and can undergo multiple rounds of initiation upon
      addition of nucleoside triphosphates. A higher concentration (0.075%) prevents
      reinitiation. In addition, we have investigated the formation of transcription
      complexes on this promoter in a S100 extract using a template competition assay.
      No stable complexes are detected with plasmid templates that contain clustered
      point mutations in the PSE nor with DNAs lacking the U6 5'-flanking region. A
      plasmid template containing mutations in the TATA element is partially deficient
      in competitive ability. Furthermore, the distal region upstream of position--148
      is necessary for efficient stable complex formation. Within this region, the
      consensus octamer motif is one component needed to form complexes that withstand
      competition by a wild-type U6 promoter. The human U2 gene enhancer ligated to the
      U6 proximal region supports formation of a complex that competes at an
      intermediate level.

PMID- 1378441
TI  - cDNA cloning and expression of bovine aspartyl (asparaginyl) beta-hydroxylase.
AB  - Aspartyl (asparaginyl) beta-hydroxylase which specifically hydroxylates 1 Asp or
      Asn residue in certain epidermal growth factor-like domains of a number of
      proteins, has been previously purified to apparent homogeneity from detergent
      solubilized bovine liver microsomes (Wang, Q., VanDusen, W. J., Petroski, C. J.,
      Garsky, V. M., Stern, A. M., and Friedman, P. A. (1991) J. Biol. Chem. 266, 14004
      14010). Three oligonucleotides, corresponding to three amino acid sequences of
      the purified hydroxylase, were used to screen bovine cDNA libraries. Several
      overlapping positive cDNA clones containing a full length open reading frame of
      754 amino acids encoding a 85-kDa protein were isolated, and a cDNA, containing
      the full length open reading frame, was constructed from two of these clones. The
      resulting clone was then transcribed and translated in vitro to produce
      recombinant protein which possessed Asp beta-hydroxylase activity. These results
      constitute proof that the protein purified from bovine liver is an Asp beta
      hydroxylase. Comparisons of deduced amino acid sequences of two other alpha
      ketoglutarate-dependent dioxygenases, prolyl-4-hydroxylase and lysyl hydroxylase,
      with that of Asp beta-hydroxylase showed no significant homologies. Indeed, Asp
      beta-hydroxylase appears to be unique as no striking homology was found with
      known protein sequences. Furthermore, structural predictions derived from the
      deduced amino acid sequence are in accord with earlier Stokes' radius and
      sedimentation coefficient determinations of the enzyme, suggesting that the
      enzyme contains a relatively compact carboxyl-terminal catalytic domain and an
      extended amino terminus. This amino-terminal region has a potential transmembrane
      type II signal-anchor domain that could direct the catalytic domain into the
      lumen of the endoplasmic reticulum.

PMID- 1378442
TI  - Transcriptional regulation in cardiac muscle. Coordinate expression of Id with a
      neonatal phenotype during development and following a hypertrophic stimulus in
      adult rat ventricular myocytes in vitro.
AB  - The transcriptional regulatory mechanisms in heart muscle that direct cardiac
      development and allow for a flexible, adaptive response to physiologic stress are
      not well understood. We demonstrate that a negative regulator of gene
      transcription termed Id that has been described predominantly in proliferating
      cell lines and in undifferentiated tissue during growth, is expressed in freshly
      isolated terminally differentiated adult rat ventricular myocytes, in contrast to
      most other tissues in the adult rat. Id mRNA expression is regulated in
      ventricular myocytes during post-natal development, peaking at the transition
      from hyperplastic to hypertrophic growth at day 17 in the rat, declining
      subsequently to lower, stable levels in adult myocytes. Although Id mRNA becomes
      undetectable in adult ventricular myocytes 48 h following isolation in the
      absence of serum, it can be rapidly reinduced by an alpha-adrenergic agonist,
      accompanied by increased protein synthesis and the reexpression, in defined
      media, of the neonatal genes prepro-ANP and skeletal muscle alpha-actin. Thus,
      the differential regulation of Id during cardiac development, the presence of Id
      mRNA in normal cardiac myocytes, and its increased expression following a
      hypertrophic stimulus all suggest a role for this transcriptional regulator in
      the control of cardiac muscle cell phenotype.

PMID- 1378443
TI  - Excision of 5'-terminal deoxyribose phosphate from damaged DNA is catalyzed by
      the Fpg protein of Escherichia coli.
AB  - Homogeneous Fpg protein of Escherichia coli has DNA glycosylase activity which
      excises some purine bases with damaged imidazole rings, and an activity excising
      deoxyribose (dR) from DNA at abasic (AP) sites leaving a gap bordered by 5'- and
      3'-phosphoryl groups. In addition to these two reported activities, we show that
      the Fpg protein also catalyzes the excision of 5'-terminal deoxyribose phosphate
      (dRp) from DNA, which is the principal product formed by the incision of AP
      endonucleases at abasic sites. Moreover, the rate of the Fpg protein catalysis
      for the 2,6-diamino-4-hydroxy-5-formamidopyrimidine-DNA glycosylase activity is
      slower than the activities excising dR from abasic sites and dRp from abasic
      sites preincised by endonucleases. The product released by the Fpg protein in the
      excision of 5'-terminal dRp from an abasic site preincised by an AP endonuclease
      is a single base-free unsaturated dRp, suggesting that the excision results from
      beta-elimination. The release of 5'-terminal dRp by crude extracts of E. coli
      from wild type and fpg-mutant strains shows that the Fpg protein is one of the
      major EDTA-resistant activities catalyzing this reaction.

PMID- 1378444
TI  - Cloning and characterization of a cDNA coding for the alpha-subunit of a
      stimulatory G protein from Schistosoma mansoni.
AB  - Guanine nucleotide-binding proteins (G proteins) mediate signals between
      serotonin receptors and adenylate cyclase in Schistosoma mansoni. A bovine Gs
      alpha cDNA probe was used to isolate a cDNA clone, SG12, encoding the entire
      alpha-subunit of a G protein of S. mansoni. The cDNA is 1897 base pairs long,
      contains an open reading frame of 1137 base pairs, and codes for a deduced
      protein of 379 amino acids. The putative protein encoded by the clone has an
      exact amino acid match with bovine Gs alpha of 65% and a 78% match when conserved
      amino acid substitutions are considered. In contrast, the exact and conserved
      matches of the schistosome alpha-subunit with bovine Gi are 41 and 61%,
      respectively. A comparison of the deduced amino acid sequence of SG12 with a
      variety of different G alpha proteins indicates that all the major structural
      features characteristic of a Gs alpha protein are present in the S. mansoni gene.
      The schistosome clone contains the putative site for ADP-ribosylation by cholera
      toxin found in Gs alpha but does not contain the ADP-ribosylation site for
      pertussis toxin present in Gi alpha. The amino acids are completely conserved at
      the GTP-binding sites. On a Northern blot, the cDNA hybridizes to a major band of
      3.1 kilobases in RNA from adult schistosomes. The message appears to be absent in
      miracidia and cercariae, but a faint 3.1-kilobase band is visible in the early
      schistosomule stage preceding adulthood. This evidence, when added to previous
      biochemical data, indicates that the expression of this gene is developmentally
      controlled.

PMID- 1378446
TI  - Association of p60c-src with endosomal membranes in mammalian fibroblasts.
AB  - We have examined the subcellular localization of p60c-src in mammalian
      fibroblasts. Analysis of indirect immunofluorescence by three-dimensional optical
      sectioning microscopy revealed a granular cytoplasmic staining that co-localized
      with the microtubule organizing center. Immunofluorescence experiments with
      antibodies against a number of membrane markers demonstrated a striking co
      localization between p60c-src and the cation-dependent mannose-6-phosphate
      receptor (CI-MPR), a marker that identifies endosomes. Both p60c-src and the CI
      MPR were found to cluster at the spindle poles throughout mitosis. In addition,
      treatment of interphase and mitotic cells with brefeldin A resulted in a
      clustering of p60c-src and CI-MPR at a peri-centriolar position. Biochemical
      fractionation of cellular membranes showed that a major proportion of p60c-src co
      enriched with endocytic membranes. Treatment of membranes containing HRP to alter
      their apparent density also altered the density of p60c-src-containing membranes.
      Similar density shift experiments with total cellular membranes revealed that the
      majority of membrane-associated p60c-src in the cell is associated with
      endosomes, while very little is associated with plasma membranes. These results
      support a role for p60c-src in the regulation of endosomal membranes and protein
      trafficking.

PMID- 1378445
TI  - Regulated export of a secretory protein from the ER of the hepatocyte: a specific
      binding site retaining C-reactive protein within the ER is downregulated during
      the acute phase response.
AB  - The half-time for secretion of the plasma protein C-reactive protein (CRP) by the
      hepatocyte decreases markedly in association with its increased synthesis during
      the acute phase response to tissue injury (Macintyre, S., D. Samols, and I.
      Kushner. 1985. J. Biol. Chem. 260:4169-4173). In studies in which subcellular
      fractions were prepared from cells incubated under pulse-chase conditions, CRP
      was found to be preferentially retained within the ER of normal hepatocytes, but
      secreted relatively efficiently in cells prepared from rabbits undergoing the
      acute phase response. On the basis of the detergent-dependency of specific
      binding of radiolabeled CRP, as well as EM visualization of biotinylated CRP
      identified with peroxidase-conjugated streptavidin, CRP was found to bind to the
      lumenal surface of permeabilized rough microsomes, while no binding was detected
      in Golgi fractions. As judged by both kinetic and equilibrium binding studies,
      rough microsomes from control rabbits were found to have two classes of specific
      binding sites for CRP; a high affinity site (Kd = 1 nM, Bmax = 1 pmol CRP/mg
      microsomal protein) as well as a much lower affinity (Kd = 140 nM) site. In
      contrast, only the lower affinity class was detected in microsomes isolated from
      rabbits undergoing the acute phase response. On nitrocellulose blots probed with
      radiolabeled CRP a 60-kD protein, distinct from BiP, was detected in extracts of
      rough microsomes isolated from control rabbits, but not in Golgi fractions or
      rough microsomes from stimulated animals. These findings correlate with previous
      observations of changes in secretion kinetics of CRP and are consistent with the
      hypothesis that the intracellular sorting of CRP could be rerouted by
      downregulation of a specific ER binding site during the acute phase response.

PMID- 1378447
TI  - Biochemical and immunological characterization of p190-calmodulin complex from
      vertebrate brain: a novel calmodulin-binding myosin.
AB  - We have recently identified a novel 190-kD calmodulin-binding protein (p190)
      associated with the actin-based cytoskeleton from mammalian brain (Larson, R. E.,
      D. E. Pitta, and J. A. Ferro. 1988. Braz. J. Med. Biol. Res. 21:213-217; Larson,
      R. E., F. S. Espindola, and E. M. Espreafico. 1990. J. Neurochem. 54:1288-1294).
      These studies indicated that p190 is a phosphoprotein substrate for calmodulin
      dependent kinase II and has calcium- and calmodulin-stimulated MgATPase activity.
      We now have biochemical and immunological evidence that this protein is a novel
      calmodulin-binding myosin whose properties include (a) Ca2+ dependent action
      activation of its Mg-ATPase activity, which seems to be mediated by Ca2+ binding
      directly to calmodulin(s) associated with p190 (maximal activation by actin
      requires the presence of Ca2+ and is further augmented by addition of exogenous
      calmodulin); (b) ATP-sensitive cross-linking of skeletal muscle F-actin, as
      demonstrated by the low-speed actin sedimentation assay; and (c) cross-reactivity
      with mAbs specific for epitopes in the head of brush border myosin I. We also
      show that p190 has properties distinct from conventional brain myosin II and
      brush border myosin I, including (a) separation of p190 from brain myosin II by
      gel filtration on a Sephacryl S-500 column; (b) lack by p190 of K(+)-stimulated
      EDTA ATPase activity characteristic of most myosins; (c) lack of immunological
      cross-reactivity of polyclonal antibodies which recognize p190 and brain myosin
      II, respectively; (d) lack of immunological recognition of p190 by mAbs against
      an epitope in the tail region of brush border myosin I; and (e) distinctive
      proteolytic susceptibility to calpain. A survey of rat tissues by immunoblotting
      indicated that p190 is expressed predominantly in the adult forebrain and
      cerebellum, and could be detected in embryos 11 d post coitus. Immunocytochemical
      studies showed p190 to be present in the perikarya and dendritic extensions of
      Purkinje cells of the cerebellum.

PMID- 1378448
TI  - Nuclear and mitochondrial inheritance in yeast depends on novel cytoplasmic
      structures defined by the MDM1 protein.
AB  - The mdml mutation causes temperature-sensitive growth and defective transfer of
      nuclei and mitochondria into developing buds of yeast cells at the nonpermissive
      temperature. The MDM1 gene was cloned by complementation, and its sequence
      revealed an open reading frame encoding a potential protein product of 51.5 kD.
      This protein displays amino acid sequence similarities to hamster vimentin and
      mouse epidermal keratin. Gene disruption demonstrated that MDM1 is essential for
      mitotic growth. Antibodies against the MDM1 protein recognized a 51-kD
      polypeptide that was localized by indirect immunofluorescence to a novel pattern
      of spots and punctate arrays distributed throughout the yeast cell cytoplasm.
      These structures disappeared after shifting mdm1 mutant cells to the
      nonpermissive temperature, although the cellular level of MDM1 protein was
      unchanged. Affinity-purified antibodies against MDM1 also specifically recognized
      intermediate filaments by indirect immunofluorescence of animal cells. These
      results suggest that novel cytoplasmic structures containing the MDM1 protein
      mediate organelle inheritance in yeast.

PMID- 1378449
TI  - Identification of a specific glycoprotein ligand for P-selectin (CD62) on myeloid
      cells.
AB  - P-selectin (CD62, GMP-140, PADGEM), a Ca(2+)-dependent lectin on activated
      platelets and endothelium, functions as a receptor for myeloid cells by
      interacting with sialylated, fucosylated lactosaminoglycans. P-selectin binds to
      a limited number of protease-sensitive sites on myeloid cells, but the protein(s)
      that carry the glycans recognized by P-selectin are unknown. Blotting of
      neutrophil or HL-60 cell membrane extracts with [125I]P-selectin and affinity
      chromatography of [3H]glucosamine-labeled HL-60 cell extracts were used to
      identify P-selectin ligands. A major ligand was identified with an approximately
      250,000 M(r) under nonreducing conditions and approximately 120,000 under
      reducing conditions. Binding of P-selectin to the ligand was Ca2+ dependent and
      was blocked by mAbs to P-selectin. Brief sialidase digestion of the ligand
      increased its apparent molecular weight; however, prolonged digestion abolished
      binding of P-selectin. Peptide:N-glycosidase F treatment reduced the apparent
      molecular weight of the ligand by approximately 3,000 but did not affect P
      selectin binding. Western blot and immunodepletion experiments indicated that the
      ligand was not lamp-1, lamp-2, or L-selectin, which carry sialyl Le(x), nor was
      it leukosialin, a heavily sialylated glycoprotein of similar molecular weight.
      The preferential interaction of the ligand with P-selectin suggests that it may
      play a role in adhesion of myeloid cells to activated platelets and endothelial
      cells.

PMID- 1378451
TI  - Domain-specific and cell type-specific localization of two types of cell wall
      matrix polysaccharides in the clover root tip.
AB  - Using immunocytochemical techniques and antibodies that specifically recognize
      xyloglucan (anti-XG), polygalacturonic acid/rhamnogalacturonan I (anti-PGA/RG-I),
      and methylesterified pectins (JIM 7), we have shown that these polysaccharides
      are differentially synthesized and localized during cell development and
      differentiation in the clover root tip. In cortical cells XG epitopes are present
      at a threefold greater density in the newly formed cross walls than in the older
      longitudinal walls, and PGA/RG-I epitopes are detected solely in the expanded
      middle lamella of cortical cell corners, even after pretreatment of sections with
      pectinmethylesterase to uncover masked epitopes. These results suggest that in
      cortical cells XG and PGA/RG-I are differentially localized not only to
      particular wall domains, but also to particular cell walls. In contrast to their
      nonoverlapping distribution in cortical cells, XG epitopes and PGA/RG-I epitopes
      largely colocalize in the epidermal cell walls. The results also demonstrate that
      the middle lamella of the longitudinal walls shared by epidermal cells and by
      epidermal and cortical cells constitutes a barrier to the diffusion of cell wall
      and mucilage molecules. Synthesis of XG and PGA/RG-I epitope-containing
      polysaccharides also varies during cellular differentiation in the root cap. The
      differentiation of gravitropic columella cells into mucilage-secreting peripheral
      cells is marked by a dramatic increase in the synthesis and secretion of
      molecules containing XG and PGA/RG-I epitopes. In contrast, JIM 7 epitopes are
      present at abundant levels in columella cell walls, but are not detectable in
      peripheral cell walls or in secreted mucilage. There were also changes in the
      cisternal labeling of the Golgi stacks during cellular differentiation in the
      root tip. Whereas PGA/RG-I epitopes are detected primarily in cis- and medial
      Golgi cisternae in cortical cells (Moore, P. J., K. M. M. Swords, M. A. Lynch,
      and L. A. Staehelin. 1991. J. Cell Biol. 112:589-602), they are localized
      predominantly in the trans-Golgi cisternae and the trans-Golgi network in
      epidermal and peripheral root cap cells. These observations suggest that during
      cellular differentiation the plant Golgi apparatus can be both structurally and
      functionally reorganized.

PMID- 1378452
TI  - Characterization of endoplasmic reticulum by co-localization of BiP and
      dicarbocyanine dyes.
AB  - The original concept of endoplasmic reticulum derived from the observation of a
      reticular network in cultured fibroblasts by electron microscopy of whole cells.
      It was previously reported that the fluorescent dye, DiOC6(3), stains a similar
      network as well as mitochondria and other organelles in living cells. Here, we
      investigate the significance of the structures labeled by DiO6(3) in CV-1 cells,
      a monkey epithelial cell line. First, we show that the network stained in living
      CV-1 cells is preserved by glutaraldehyde fixation and then we co-label it with
      an antibody against BiP (immunoglobulin binding protein), a protein commonly
      accepted to be present in the endoplasmic reticulum. Anti-BiP labeled the same
      network as that labeled by DiOC6(3), so this network now is identified as being
      part of the endoplasmic reticulum. DiOC6(3) labels many other membrane
      compartments in addition to the endoplasmic reticulum. This, along with its
      lipophilic properties, suggests that DiOC6(3) stains all intracellular membranes.
      However, the extensive reticular network in the thin peripheral regions of
      cultured cells is easily distinguished from these other membranes. Thus, staining
      by DiOC6(3) is a useful method for localizing the endoplasmic reticulum,
      particularly in thin peripheral regions of cultured cells.

PMID- 1378453
TI  - Affinity chromatography of serine proteinases from the bovine intervertebral disc
      on BPTI-Separon HEMA 1000.
AB  - A method for the purification of serine proteinases from the bovine
      intervertebral disc using affinity chromatography on basic pancreatic trypsin
      inhibitor (BPTI) immobilized to the hydroxyalkyl methacrylate copolymer Separon
      HEMA 1000 E is reported. Its advantage is the possibility of obtaining serine
      proteinases without an artificial alteration in relative molecular mass.

PMID- 1378450
TI  - CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to
      cytokine-activated endothelial cells.
AB  - Neutrophil adherence to cytokine-activated endothelial cell (EC) monolayers
      depends on the expression of the endothelial leukocyte adhesion molecule-1 (ELAM
      1). The ligand for ELAM-1 is the sialylated Lewis-x antigen (SLe(x)) structure.
      The selectin LAM-1 (or LECAM-1) has been described as one of the SLe(x)
      presenting glycoproteins involved in neutrophil binding to ELAM-1. Other
      presenter molecules have not yet been described. Our data demonstrate that the
      carcinoembryonic antigen (CEA)-like surface molecules on neutrophils--known as
      the nonspecific cross-reacting antigens (NCAs)--are involved in neutrophil
      adherence to monolayers of IL-1-beta-activated EC. The NCAs are recognized by
      CD66 (NCA-160 and NCA-90) and CD67 (NCA-95). Because NCA-95 and NCA-90 have
      previously been found to be phosphatidylinositol (PI)-linked, paroxysmal
      nocturnal hemoglobinuria (PNH) neutrophils (which lack PI-linked surface
      proteins) were tested as well. PNH neutrophils showed a diminished binding to
      activated EC. CD66 (on PNH cells still recognizing the transmembrane NCA-160
      form) still inhibited the adherence of PNH cells to IL-1-beta-activated EC, but
      to a limited extent. Soluble CEA(-related) antigens inhibited normal neutrophil
      adherence as well, whereas neutrophil transmigration was unaffected. Sialidase
      treatment as well as CD66 preclearing abolished the inhibitory capacity of the
      CEA(-related) antigens. The binding of soluble CEA antigens to IL-1-beta
      pretreated EC was blocked by anti-ELAM-1. These soluble antigens, as well as the
      neutrophil NCA-160 and NCA-90, both recognized by CD66 antibodies, presented the
      SLe(x) determinant. Together, these findings indicate that the CD66 antigens
      (i.e., NCA-160/NCA-90) function as presenter molecules of the SLe(x)
      oligosaccharide structures on neutrophils that bind to ELAM-1 on EC.

PMID- 1378454
TI  - Levels of immunoglobulin G antibodies against defined epitopes of the L1 and L2
      capsid proteins of human papillomavirus type 6 are elevated in men with a history
      of condylomata acuminata.
AB  - Sera from 159 men attending the sexually transmitted disease clinic at Karolinska
      Hospital, Stockholm, Sweden, were analyzed for the presence of immunoglobulin A
      (IgA) and IgG antibodies to a panel of synthetic peptides derived from the E2,
      L1, and L2 regions of the human papillomavirus types 1 (HPV 1), 6, 8, 11, 16, 18,
      31, and 33. The study subjects were divided into three groups: (i) asymptomatic
      men with no history of genital warts who served as controls, (ii) men with
      visible condylomata, and (iii) men who had previously been afflicted with
      condylomata. There were no significant differences in antibody titers for any of
      the HPV 6- or 11-derived peptides among patients with current condylomata and the
      controls. For the peptide from L1 of HPV 6, there was an increase in the IgG
      titers among men with previous condylomata compared with the titers for the
      controls (52% versus 27% seropositivity; P less than 0.05). Also, for the peptide
      from L2 of HPV 6, there was an increase in the IgG titers among men who had been
      afflicted with condylomata previously (P less than 0.05). Increased IgA antibody
      titers against an HPV 16-derived peptide and an HPV 18-derived peptide were also
      detected. For the peptides from L1 and L2 of HPV 6, the study was extended to an
      additional group of 127 males attending the sexually transmitted disease clinic
      at Huddinge Hospital in southern Stockholm. Again, significantly increased
      antibody levels were detected only for IgG and only among asymptomatic men with a
      history of condylomata (P < 0.01 for the L1 peptide and P < 0.05 for the L2
      peptide). The results suggest that the IgG response against the late proteins of
      HPV 6 reflects mainly previous exposure to the virus rather than ongoing viral
      disease.

PMID- 1378456
TI  - Use of Hemo-De to eliminate toxic agents used for concentration and trichrome
      staining of intestinal parasites.
AB  - In a blind comparison, 465 randomly collected clinical fecal specimens were
      examined. Hemo-De was found to be an excellent replacement for ethyl acetate in
      the concentration procedure and for carbol-xylene and xylene in the trichrome
      staining procedure. Elimination of toxic reagents, combined with its lower cost,
      makes Hemo-De the preferred choice in routine parasitology examinations.

PMID- 1378455
TI  - Antibody responses to lipid A, core, and O sugars of the Pseudomonas aeruginosa
      lipopolysaccharide in chronically infected cystic fibrosis patients.
AB  - Enzyme-linked immunosorbent assays were developed separately for the three main
      parts of the Pseudomonas aeruginosa lipopolysaccharide (LPS) molecule, namely,
      lipid A, core, and O polysaccharide. Anti-lipid A, anticore, and anti-O
      polysaccharide antibodies were measured in serum samples from 12 patients with
      cystic fibrosis (CF) in a longitudinal study covering the period before P.
      aeruginosa infection was established through at least 5 years of chronic
      infection. The serum antibody response to all parts of the P. aeruginosa LPS
      molecule increased during the course of chronic infection. The increase in anti
      lipid A antibodies was specific for P. aeruginosa lipid A, since no increase in
      anti-Escherichia coli lipid A antibodies was seen. Immunoglobulin G, A, and M
      (IgG, IgA and IgM) antibodies were all involved in the specific systemic response
      to P. aeruginosa lipid A, core, and the O polysaccharides. IgG and IgA levels in
      particular increased during the course of infection and were significantly higher
      than the antibody increase seen with age in a healthy control group. The local
      immune response in the lungs was investigated by measuring IgG, IgA, and IgM
      antibodies to the separate parts of the P. aeruginosa LPS molecule in sputum
      samples from 18 CF patients with at least a 5-year history of chronic P.
      aeruginosa infection. Antibodies detected in sputum were mainly anti-lipid A and
      anti-O polysaccharide antibodies of the IgG and IgA isotypes. Very high IgA anti
      lipid A titers were detected in sputum samples from some CF patients.

PMID- 1378457
TI  - Sources of presumptive glutamatergic/aspartatergic afferents to the mediodorsal
      nucleus of the thalamus in the rat.
AB  - The distribution of presumptive glutamatergic and/or aspartatergic neurons
      retrogradely labeled following injections of 3HD-aspartate into the mediodorsal
      nucleus of the thalamus (MD) in the rat was compared to the distribution of
      neurons labeled by comparable injections of the nonspecific retrograde tracer
      wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Cells
      retrogradely labeled by WGA-HRP were found in the prefrontal and agranular
      insular cortices; in forebrain structures such as the amygdaloid complex, the
      piriform cortex, the ventral pallidum and the reticular nucleus of the thalamus;
      and in several different parts of the brainstem, such as the superior colliculus,
      central grey, and substantia nigra, pars reticulata. Some, but not all, of these
      projections are presumably glutamatergic and/or aspartatergic. The projections to
      MD from the prefrontal and agranular insular cortices are well labeled with 3H-D
      aspartate, as are projections from the anterior cortical amygdaloid nucleus.
      Projections from the superior colliculus to the lateral portion of MD also label
      with this tracer. However, other forebrain and brainstem projections to MD are
      not labeled with 3H-D-aspartate, and apparently do not use glutamate or aspartate
      as a neurotransmitter. These include the projections from the basal and accessory
      basal amygdaloid nuclei, as well as possibly GABAergic projections from the
      ventral pallidum and the substantia nigra, pars reticulata. A small fraction of
      the cells in the piriform cortex that project to MD label with 3H-D-aspartate,
      suggesting that this projection may be heterogeneous. In other experiments,
      presumptive GABAergic projections to MD were studied by using 3H-GABA as a
      retrograde tracer. Although in these cases the thalamic reticular nucleus is well
      labeled, the ventral pallidum and the substantia nigra, pars reticulata are only
      poorly labeled. Pallidal projections to the ventromedial thalamic nucleus (VM),
      which are likely to be GABAergic, were also studied with this technique. After
      injections of 3H-GABA into VM, only a few cells in the substantia nigra, pars
      reticulata, or entopeduncular nucleus were labeled. This result suggests 3H-GABA
      has limited usefulness as a transmitter-specific retrograde tracer.

PMID- 1378458
TI  - Olfactory bulb organization and development in Monodelphis domestica (grey short
      tailed opossum).
AB  - The olfactory bulbs of adult and developing Monodelphis domestica were examined
      with a number of techniques. Golgi, Nissl, and Timm stains as well as
      acetylcholinesterase histochemistry revealed a high degree of order within the
      adult bulb. All major cell classes characteristic of most mammalian species were
      observed. Tufted cells appeared to be restricted to the superficial portion of
      the external plexiform layer. Developing Monodelphis pups were examined with
      Nissl-stained semithin sections and with immunocytochemistry for tyrosine
      hydroxylase, microtubule-associated protein 2, vimentin, and glial fibrillary
      acidic protein. Newborn pups are extremely immature, with few postmitotic cells
      present in the forebrain. Considerable maturation occurs over the first four
      postnatal weeks, and by postnatal day 30, the bulb assumes an adult-like
      organization. The extreme immaturity of the bulb at birth, coupled with its
      strict organization, suggest that Monodelphis is a particularly appropriate
      species for experimental examinations of olfactory system development.

PMID- 1378459
TI  - Mapping human T cell epitopes on phospholipase A2: the major bee-venom allergen.
AB  - Phospholipase A2 (PLA2), the major bee-venom allergen, was purified by gel
      filtration, inactivated by denaturing, and carboxymethylating its cysteine
      residues. Peripheral blood mononuclear cells from an individual (HLA-DR2 [15],
      Dw52, DQ1 and DQ3) allergic to bee stings were used to generate cell lines
      specific for PLA2 and a control antigen, tetanus toxoid. These lines were 90%
      CD3+, 64% CD4+ and 20% CD8+ by fluorocytometry analysis. T-lymphocyte epitope
      mapping done with 12 overlapping synthetic peptides of PLA2 revealed two
      immunodominant epitopes. These epitopes correspond to amino acid sequences 50 to
      69 and 83 to 97 of PLA2. Cytokine interleukin-4 and Interferon-gamma secretion
      was studied from PLA2- and tetanus toxoid-specific cell lines. Interleukin-4
      secretion was common to both cell lines but only tetanus-toxoid cell lines
      secreted interferon-gamma. No interferon-gamma was found to be secreted by PLA2
      specific cell line in response to stimulation by PLA2 or the two immunodominant
      peptides.

PMID- 1378460
TI  - Regulation of human basophil activation. III. Impairment of the inhibitory effect
      of Na+ on IgE-mediated histamine release in patients with allergic rhinitis.
AB  - We recently observed that external Na+ inhibited the IgE-dependent human basophil
      histamine release (HR) in normal subjects. In this article we report differences
      in the Na+ effect on basophil HR between normal subjects (n = 16) and age matched
      patients with allergic rhinitis (AR) (n = 18). As expected, in vitro anti-IgE
      stimulated basophils from the group with AR released greater amounts of histamine
      than basophils from the normal group. However, removal of external Na+ (and
      replacement by N-methyl-D-glucamine) abolished this difference between the two
      groups. HR in the normal group increased to the same high level as that of the
      group with AR. By contrast, the release of histamine in the group with AR was not
      further increased by Na+ removal. Although high releasers were more frequent in
      the group with AR, the absence of effect after Na+ removal was not due to the
      high basal release level (in the presence of Na+) because no effect after Na+
      removal was also observed with medium releasers. These results strongly suggest
      that increased basophil HR in populations with AR, and possibly in other allergic
      populations, is linked to a defect in the inhibitory effect of Na+.

PMID- 1378461
TI  - Intracellular events in anti-IgE nonreleasing human basophils.
AB  - Histamine release (HR) after activation of human basophils with anti-IgE
      demonstrates a great variability among different donors. To elucidate the
      biochemical basis of this phenomenon, we studied the activation of purified
      basophils from donors that barely demonstrated HR (less than 7%) after
      stimulation by anti-IgE, although IgE was present on these cells and formyl
      methionyl-leucyl-phenylalanine (fMLP)-induced HR was normal. Basophils from anti
      IgE "nonreleasers" demonstrated, in contrast to cells from "releasers," hardly
      any changes in cytosolic-free Ca++ concentration after addition of anti-IgE.
      However, anti-IgE treatment of basophils from these anti-IgE nonreleasers
      resulted in at least two intracellular changes. First, a profound inhibition
      (54.2% +/- 4.2%) of a subsequent fMLP-induced HR was observed. This inhibition
      caused by anti-IgE was also observed in basophils from anti-IgE releasers treated
      with wortmannin, an inhibitor of the anti-IgE-induced HR. The time course of the
      inhibition induced by wortmannin plus anti-IgE on the fMLP-induced HR (half-life
      maximum, 4 minutes; time of maximum concentration, 10 minutes) was comparable to
      the time course of the anti-IgE-induced HR. Second, anti-IgE did induce homotypic
      aggregation in these anti-IgE-nonreleasing basophils, like in anti-IgE-releasing
      basophils. These studies indicate that basophils not responding to anti-IgE with
      HR or cytosolic-free Ca++ concentration changes do generate intracellular signals
      that inhibit the subsequent response to a heterologous stimulus and induce
      homotypic aggregation.

PMID- 1378462
TI  - Cytogenetic analysis of pulmonary lavage and bone marrow cells of rats after
      repeated formaldehyde inhalation.
AB  - Cytogenetic analyses were conducted on bone marrow and pulmonary lavage cells
      from rats that received repeated inhalation exposures to formaldehyde. Male
      Sprague-Dawley rats were exposed to 0, 0.5, 3, or 15 ppm formaldehyde for 6 h per
      day, 5 days per week, for 1 and 8 weeks. There was no significant increase in
      chromosomal abnormalities in the bone marrow cells of formaldehyde-exposed rats
      relative to controls. There was a statistically significant increase in
      chromosomal aberrations in the pulmonary lavage cells from rats that inhaled 15
      ppm. There were 7.6 and 9.2% of the scored pulmonary lavage cells that had
      aberrations following 1 and 8 weeks, respectively, of 15 ppm formaldehyde
      exposure (with control levels of 3.5 and 4.8%, respectively). The predominant
      damage seen was chromatid breaks. These findings indicate that marginal but
      statistically significant genotoxic effects could be detected locally in lung
      alveolar macrophages, but not distally in bone marrow, following repeated
      formaldehyde exposures only at a high concentration that is carcinogenic to rats.
      The biological significance of this effect is uncertain since formaldehyde is not
      considered to be a lung carcinogen in rats.

PMID- 1378463
TI  - Neonatal capsaicin-treatment in mice: effects on pancreatic peptidergic nerves
      and 2-deoxy-D-glucose-induced insulin and glucagon secretion.
AB  - It is not known whether sensory nerves are involved in the insulin, glucagon or
      glucose responses to autonomic nerve activation induced by 2-deoxy-D-glucose (2
      DG). We therefore treated mice neonatally with capsaicin which permanently
      destroys sensory afferent nerve fibers. Immunohistochemistry of the pancreas at
      13-14 weeks of age revealed a substantial reduction of calcitonin gene-related
      peptide (CGRP)-immunoreactive nerves and a partial reduction of substance P
      immunoreactive nerves. In contrast, no effect was observed on galanin
      immunoreactive nerves. At age 10-12 weeks, the mice were injected intravenously
      with 2-DG (500 mg/kg). In controls, 2-DG stimulated insulin and glucagon
      secretion and induced hyperglycemia (P less than 0.01). Capsaicin treatment
      partially reduced the glucose and glucagon responses to 2-DG (P less than 0.01).
      In contrast, the insulin response to 2-DG was not affected by capsaicin. It is
      concluded that the mouse pancreas contains capsaicin-sensitive sensory CGRP- and
      substance P-immunoreactive nerve fibers, whereas the galanin-immunoreactive nerve
      fibers are not sensitive to capsaicin. Furthermore, capsaicin-sensitive sensory
      nerve fibers are partially involved in 2-DG-induced glucagon secretion and
      hyperglycemia, whereas sensory nerves are not involved in 2-DG-induced insulin
      secretion.

PMID- 1378464
TI  - Carpal collapse and Sudeck's atrophy.
AB  - Acute posttraumatic (Sudeck's) atrophy of the upper extremity is well known. The
      symptoms and signs are out of proportion to what is to be expected from the
      inciting event. Typically, bone atrophy is characterized by a focal, patchy,
      periarticular demineralization pattern, which is usually transient.
      Remineralization occurs after successful treatment. This report describes a
      typical case of the clinical syndrome after a wrist sprain but with carpal
      dissolution and collapse before remineralization.

PMID- 1378465
TI  - Histogenesis of human stomach cancers based on assessment of differentiation.
AB  - The histogenesis of human stomach cancer was assessed based on the determination
      of the differentiation of component cancer cells. Specimens of 229 surgically
      obtained primary gastric cancers were used. Histochemical staining of mucins
      [paradoxical concanavalin A, galactose oxidase-Schiff (GOS), and sialidase-GOS
      sequence] and immunohistochemical demonstration of pepsinogens (Pg) I and II
      allowed the differentiation of gastric elements including mucous neck cells,
      pyloric gland cells, and surface mucous cells as well as intestinal goblet and
      absorptive cell types. Of 122 papillary and tubular adenocarcinomas, the
      proportion consisting mainly of intestinal type cells increased with progression
      from 22.9% (early) to 41.9% (advanced). Similarly, intestinal features increased
      with progression from 8.3% (early) to 25.4% (advanced) in the 107 poorly
      differentiated adenocarcinomas, signet ring cell carcinomas, and mucinous
      adenocarcinomas studied. A phenotypic shift from gastric- to intestinal-type
      expression was thus observed with progression of each histologic type of gastric
      cancer. Furthermore, tumors consisting mainly of gastric-type cells were commonly
      found within intestinal metaplastic mucosa, suggesting that this latter is not a
      preneoplastic lesion for gastric cancers in humans.

PMID- 1378467
TI  - Synthesis and macromolecular organization of gastrointestinal mucin: evidence for
      the origin of mucin "link protein".
AB  - Mucus glycoproteins (mucins), the principal determinants of mucus protective
      qualities and mucosal defense, have been studied extensively to define
      pathological aberrations in relation to gastrointestinal disease. Recent work
      from our laboratory provided evidence as to the initial stages of
      gastrointestinal mucin synthesis, the molecular size of the apomucin, and its
      macromolecular organization. Using monoclonal antibodies (MAbs) against apomucin
      (clone 1H7), O-glycosylated with N-acetylgalactosamine apomucin (clone 2B4), and
      that against carboxyl terminal of the apomucin (clone 3G12), the mucin
      synthesizing polysomes were isolated and glycosylated peptides ranging in size
      from 6 to 60 kDa identified. In vitro synthesis in a cell-free system also
      afforded 60- to 64-kDa products recognized by 1H7 and 3G12 antimucin MAbs. The
      results obtained provided evidence that the mucin core consists of 60-kDa peptide
      that at the cotranslational stage is O-glycosylated with N-acetylgalactosamine.
      Studies on mucin polymer assembly revealed that mucin preparations prepared by
      equilibrium density gradient centrifugation and Sepharose 2B chromatography are
      not completely purified and contain DNA and extraneous proteins. The evidence was
      obtained that so-called mucin "link protein", a 118-kDa glycopeptide, is a N
      glycosylated fragment of fibronectin, whereas the supposedly native undergraded
      mucin isolated by Carlstedt et al. was found to contain mucin-fibronectin-DNA
      complexes. The general picture that emerged from the studies is that the pure
      mucin consists of 60 kDa glycosylated peptides only. The carboxyl terminal (8- to
      12-kDa fragment) of these peptides is not glycosylated (naked) and is responsible
      for mucin interaction with fibronectin and other fibronectin-like extracellular
      matrix proteins. Although the formation of the mucosal coat depends on many other
      factors and extracellular components, our findings on mucin structure and
      interaction with the extracellular matrix proteins provide an explanation as to
      the possible mechanism of mucin adherence to the epithelial surfaces.

PMID- 1378466
TI  - Mechanism of Helicobacter pylori pathogenesis: focus on mucus.
AB  - Although the clinical data provide increasingly convincing indications that
      Helicobacter pylori (H. pylori) is a causative factor in gastritis and peptic
      ulcer, the advances toward the clear understanding of this bacterium's pathogenic
      action are slow in coming. Having a niche bordering two major perimeters of
      gastric mucosal defense, H. pylori is capable of exerting detrimental effects on
      the mucus layer, as well as surface cells of the gastric epithelium. To cause
      such an effect, the bacteria must first, however, attach to the mucosa. Our
      findings indicate that this attachment involves specific structures on the
      epithelial cell surfaces, namely lactosylceramide sulfate and GM3 ganglioside.
      The analysis of the glycolipid distribution pattern in different regions of human
      stomach revealed that the antral mucosal content of GM3 and lactosylceramide
      sulfate are considerably higher than that of the fundus, which may account for
      the prevalence of H. pylori colonization of the antrum. We have also established
      that H. pylori causes considerable untoward changes in gastric mucus coat
      integrity. These changes are reflected in the loss of protective qualities of
      mucus due to the action of H. pylori-elaborated proteases and lipases. The result
      of H. pylori protease action is disintegration of the polymeric structure of
      mucin, whereas the elaborated lipases and phospholipase A2 in particular result
      in mucus lipid degradation, loss of mucosal surface, hydrophobicity, and
      lysophospholipid generation. The lytic activity of the resulting
      lysophospholipids is detrimental not only to mucus gel integrity, but even more
      so to the cell membrane of gastric epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378468
TI  - Use of fluorescent hydrophobic dyes in establishing the presence of lipids in the
      gastric mucus gel layer.
AB  - The hydrophobic property of crude samples of canine and porcine mucus was
      demonstrated by its binding and reactivity with two fluorescent dyes, 1
      anilinonaphthalene-8-sulfonic acid (ANS) and 1,6-diphenyl-1,3,5-hexatriene (DPH).
      The contribution of lipids to these hydrophobic binding sites was indicated by
      our observations that the DPH-induced fluorescence of both porcine and canine
      gastric mucus was reduced greater than 75% after lipid extraction. Fluorescence
      microscopy revealed an extracellular band of intense reactivity in association
      with the mucus gel layer overlying the rat gastric mucosa that was abolished if
      the frozen sections were pretreated with lipid solvents. When rats pretreated
      with indomethacin were injected with a cytoprotective dose of 16,16-dimethyl
      PGE2, there was an increase in fluorescence of the gastric perfusate treated with
      ANS, suggesting that hydrophobic factors, perhaps lipids, were being secreted in
      association with mucus. These extracellular lipids may play an important role in
      conferring protective barrier properties to the mucus gel layer.

PMID- 1378469
TI  - Effects of sofalcone administration on the physicochemical properties of gastric
      mucus.
AB  - The effect of prolonged administration of an antiulcer drug, sofalcone, on the
      physicochemical properties of gastric mucus was investigated. The experiments
      were conducted with two groups of rats in which one group received a dose of 100
      mg/kg of sofalcone twice daily for three consecutive days, and the control group
      received daily doses of vehicle. The rats were killed 16 h after the last dose,
      their stomachs dissected, and the mucosa subjected to physicochemical
      measurements. The results revealed that sofalcone evoked a 23% increase in mucus
      gel thickness, and its content of sulfo- and sialomucins increased by 54 and 25%,
      respectively. These changes in mucus with sofalcone were accompanied by a 16%
      increase in H+ retardation capacity, twofold increase in viscosity, and a 39%
      increase in the gel hydrophobicity. The mucus elaborated in the presence of
      sofalcone exhibited a 10% lower content of protein, 30% higher content of
      carbohydrate, and 18% higher content of total lipids, which were particularly
      enriched (20%) in phospholipids and contained 67% more covalently bound fatty
      acids. Furthermore, the high molecular weight mucus glycoprotein form accounted
      for about 30% of gel mucin in the control group, whereas its content in mucus gel
      of animals receiving sofalcone reached 50%. The results indicate that sofalcone
      enhances the protective qualities of the mucus component of the gastric mucosal
      barrier and hence strengthens the gastric mucosal integrity.

PMID- 1378470
TI  - Dextran, a hapten carrier in immunoassays for s-triazines. A comparison with
      ELISAs based on hapten-protein conjugates.
AB  - A conjugate of 2-aminohexylamino-4-ethylamino-6-isopropylamino-1,3,5-triazine
      (AHA), a derivative of the herbicide atrazine, with dextran as carrier has been
      synthesized and used as the coating antigen in ELISA procedures. The
      quantification of terbutryn, atrazine and prometryn in ELISA formats using
      monoclonal antibodies and the AHA-dextran conjugate was at least as sensitive as
      ELISAs using protein conjugates as immobilized antigens (sensitivity at 50% B/B0
      was 0.4-0.6 micrograms/l for terbutryn). Formats with immobilized antibody and
      enzyme labelled AHA proved to be less sensitive (1.5 micrograms/l for terbutryn).
      The observed differences in sensitivity do not apparently result from structural
      effects of the carrier bound hapten since all conjugates were prepared with one
      form of the hapten, 2-aminohexylamino-atrazine, which was covalently linked via
      its amino function to the carriers or enzymes.

PMID- 1378471
TI  - A simple technique for the determination of kappa and lambda immunoglobulin light
      chain expression by B cells in whole blood.
AB  - This article describes the development of a simple technique by which the numbers
      of surface immunoglobulin expressing cells can be analysed by dual fluorescence
      flow cytometry in samples of whole blood. We have compared the results obtained
      using this procedure with those obtained using samples prepared by traditional
      density gradient centrifugation, and demonstrate an excellent correlation between
      the two techniques. The method is applicable both to blood samples from normal
      individuals and from patients with B cell malignancies such as B-CLL and B-NHL.
      We have also confirmed previous findings that density gradient centrifugation may
      preferentially deplete certain lymphocyte subsets. This technique offers the
      following advantages: (i) it is rapid, (ii) it is accurate, (iii) it is reliable,
      (iv) it is useful in cases of lymphopenia, and (v) it requires only a small
      volume of blood. It is likely to be applicable to other situations in which the
      presence of serum factors interfere with antibody staining in whole blood.

PMID- 1378472
TI  - Production of epitope specific monoclonal IgG antibodies to HLA class II
      molecules by combining in vivo and in vitro immunization.
AB  - To study the expression of HLA-DQ beta chain alleles associated with type 1
      diabetes, mAbs were generated from mice immunized with synthetic peptides
      representing allelic HLA-DQw7 and HLA-DQw8 beta chain sequences. The splenocytes
      from immunized mice were fused with myeloma cells, either immediately after or
      following additional in vitro boosting with peptide. Peptide-specific mAbs,
      predominantly of the IgG isotype, were isolated only from in vitro boosted
      splenocytes. Immunoblot analysis showed that several of the mAbs cross-reacted
      with DQ beta chain molecules. One mAb to a peptide representing DQw8 beta
      position [49-60] specifically recognised the DQw8 beta chain. Three mAbs to a
      peptide representing DQw8 beta position [39-52] specifically recognised an
      epitope consisting of Gly-Val-Tyr in position 45-47, i.e., all DQ beta alleles
      except DQw7 beta (position 45-47: Glu-Val-Tyr) and DQw2 beta (position 45-47; Gly
      Glu-Phe). In FACS analysis these mAbs bound lymphocytes with the same specificity
      as found by immunoblotting analysis. Thus, by combining in vivo and in vitro
      immunization we have generated a number of epitope specific monoclonal IgG
      antibodies that distinguish closely related HLA-DQ beta chain alleles in
      predetermined positions.

PMID- 1378473
TI  - An immunochemical analysis of the human nuclear phosphoprotein p53. New
      monoclonal antibodies and epitope mapping using recombinant p53.
AB  - Somatic mutation of the p53 gene is a very frequent event in the development of
      human neoplasia, and germ line mutations in p53 are responsible for an inherited
      cancer susceptibility syndrome. Many of the mutations in p53 found in human
      tumours are point mutations that result in the substitution of a single amino
      acid in the protein. These point mutant proteins are much more stable than the
      normal protein and the mutant product accumulates to a high level which permits
      important information about p53 expression to be obtained by immunochemical
      analysis. Using bacterial expression systems to produce fragments of human p53 we
      have isolated and characterized new monoclonal antibodies to p53. These
      antibodies are suitable for the measurement of p53 in ELISA, immunoblotting and
      immunoprecipitation analyses. They are especially useful in immunohistochemistry
      as they are able to react strongly with p53 in conventionally fixed and processed
      histological sections.

PMID- 1378474
TI  - Studies of the low dose 'hook' effect in a competitive homogeneous immunoassay.
AB  - The interactions of two monoclonal antibodies with human growth hormone (hGH)
      have been investigated. The individual antibodies showed normal behavior in a
      competitive binding assay, but mixtures of the antibodies demonstrated a 'hook'
      attributable to cooperative interactions. Cooperativity was observed in
      titrations which preceded the competitive binding assay. Size exclusion
      chromatographic data suggest that the cooperativity is explained by the formation
      of higher molecular weight complexes (up to 700 kDa). The major complex is
      probably linear, consisting of three antibody molecules. Circular and linear
      complexes with four antibody molecules (octameric complexes) are also possible.
      Theoretical models also support the formation of cyclic complexes in a
      competitive binding assay.

PMID- 1378475
TI  - Studies of the 'hook' effect in the one-step sandwich immunoassay.
AB  - The one-step sandwich immunoassay is increasingly replacing the traditional two
      step immunoassay due to obvious advantages such as assay speed. However, the one
      step sandwich immunoassay suffers from the 'hook' effect irrespective of the
      analyte characteristics. The 'hook' effect is dependent primarily on the analyte
      concentration. Three different model analytes, human growth hormone (hGH), the
      dimeric form of hGH (D-hGH, having a discrete number of repeating epitopes) and
      ferritin (multiple epitopes) having different immunological properties have been
      employed in studies of the one-step sandwich immunoassay. The characteristics of
      each of the model analytes offer new insights into general guidelines for assay
      procedures. These guidelines permit rapid optimization of assay conditions for an
      immunoassay without a priori knowledge of the immunological characteristics of
      the antibody or antigen. Both experimental and theoretical data show several
      instances where high capacity solid-phase antibodies can effectively shift the
      'hook' to relatively higher analyte concentrations. The effect of the
      concentration of labeled antibody on assay response was examined theoretically.

PMID- 1378476
TI  - Multiple epitope interactions in the two-step sandwich immunoassay.
AB  - The 'hook' effect as related to the two-step sandwich immunoassay has been
      investigated experimentally and theoretically. The multiple epitope interactions
      between the analyte and the labeled antibody cause a 'hook' in the two-step
      sandwich immunoassay. Three different analytes and monoclonal antibodies were
      chosen to carefully demonstrate the effect of the analyte characteristics on this
      immunoassay. Two monoclonal antibodies against two different epitopes of
      biosynthetic human growth hormone (hGH) was the simplest model for this study.
      The sandwich immunoassay for hGH shows no 'hook' effect. The non-covalent dimeric
      form of hGH (D-hGH) possesses two repeating epitopes which is the simplest model
      for an analyte having a discrete number of repeating epitopes. The D-hGH assay
      demonstrated a 'hook' effect in the two-step sandwich immunoassay if the labeled
      antibody was allowed to interact with more than one epitope. In a third system
      multiple epitope interactions with the labeled antibody were observed using
      ferritin. The effect of the analyte concentration and the liquid-phase antibody
      have been examined to elucidate the nature of these various interactions. The
      cause of the 'hook' effect in the two-step sandwich immunoassay is attributed to
      the desorption of the bound analyte due to a conformational change after the
      labeled antibody interacts with several epitopes of the adsorbed analyte.

PMID- 1378477
TI  - A simple approach to improving sensitivity in a one-step monoclonal antibody
      based ELISA for human IIbIIIa using multiple conjugates.
AB  - This paper describes an approach which can be used to increase both the speed and
      the sensitivity of a monoclonal antibody (MAb) based ELISA for human IIbIIIa by
      using a mixture of enzyme labeled MAbs (conjugates) and a one step incubation
      format (where analyte and conjugates were incubated simultaneously for 2 h in the
      MAb coated well). A simple competitive blocking method is described for mapping
      the relative epitopes of five monoclonal antibodies (MAbs) with minimum
      preparation of enzyme conjugate. This method permits the selection of three MAbs
      which recognize distinctly different epitopes, and are suitable for use in a one
      step ELISA format. Compared to the regular two step ELISA using two MAbs, this
      simple modification improves the assay sensitivity by three-fold and decreases
      the incubation time by 75%, while maintaining a high level of precision (2-15%).
      The assay is very specific and can accurately measure both recombinant and native
      IIbIIIa.

PMID- 1378478
TI  - Cellular localization of mRNA for cellular retinoic acid-binding protein II and
      nuclear retinoic acid receptor-gamma 1 in retinoic acid-treated human skin.
AB  - We have previously shown that cellular retinoic acid-binding protein II (CRABP
      II), but not cellular retinoic acid-binding protein I (CRABP-I), mRNA expression
      is markedly induced in human skin by topical retinoic acid. In the present study,
      we have investigated the pattern of expression of CRABP-II transcripts in 4-d RA
      treated human skin by non-radioactive in situ hybridization (n = 5) and Northern
      analysis (n = 4). RA induced accumulation of CRABP-II transcripts throughout the
      epidermis, dermal fibroblasts, and endothelial cells as determined by in situ
      hybridization. In skin treated with vehicle, a faint hybridization signal was
      observed only in basal layers of the epidermis consistent with low-level
      expression of CRABP-II mRNA. RA-mediated accumulation of CRABP-II transcripts in
      skin was also confirmed by Northern analysis. Neither RA nor vehicle induced
      significant changes in nuclear RA receptor-gamma 1 or keratin 5 gene expression
      in skin as determined by in situ or Northern hybridization. These results
      indicate that RA-induced CRABP-II mRNA accumulation is primarily localized to
      spinous and granular layers in epidermis, and in superficial dermis.

PMID- 1378479
TI  - Nuclear proteins involved in transcription of the human K5 keratin gene.
AB  - Keratin K5 is expressed in the basal layer of stratified epithelia in mammals and
      its synthesis is regulated by hormones and vitamins such as retinoic acid. The
      molecular mechanisms that regulate K5 expression are not known. To initiate
      analysis of the protein factors that interact with the human K5 keratin gene
      upstream region, we have used gel-retardation and DNA-mediated cell-transfection
      assays. We found five DNA sites that specifically bind nuclear proteins. DNA
      protein interactions at two of the sites apparently increase transcription
      levels, at one decrease it. The importance of the remaining two sites is, at
      present, unclear. In addition, the location of the retinoic acid and thyroid
      hormone nuclear receptor action site has been determined, and we suggest that it
      involves a cluster of five sites similar to the consensus recognition elements.
      The complex constellation of protein binding sites upstream from the K5 gene
      probably reflects the complex regulatory circuits that govern the expression of
      the K5 keratin in mammalian tissues.

PMID- 1378480
TI  - Bovine coronavirus peplomer glycoproteins: detailed antigenic analyses of S1, S2
      and HE.
AB  - Forty-four monoclonal antibodies (MAbs) to the G110 isolate of bovine enteric
      coronavirus were used for the characterization of the peplomer proteins S and HE.
      Fourteen of these MAbs reacted with HE and the remaining 30 with the products of
      the S gene, S1 (19 MAbs), S2 (six MAbs) and gp200 (five MAbs). S1 and HE were
      found to carry major neutralization determinants, and S1 appeared to elicit the
      production of the MAbs displaying the highest neutralizing activity. The
      topography of the epitopes was assessed by means of a competitive binding assay;
      the 44 MAbs defined four independent antigenic domains on S1, two on S2, one on
      gp200 and two on HE. All the neutralizing anti-S1 MAbs mapped in antigenic sites
      A and B and all the neutralizing anti-HE MAbs in HE-B. Antigenic site S1-B was
      further subdivided into four subsites. Functional mapping was performed by
      testing a library of neutralization-resistant mutants against the neutralizing
      MAbs. Analysis of their reactivity in a neutralization test confirmed the overall
      distribution of epitopes in S1-B and HE-B.

PMID- 1378481
TI  - Differential inhibitory effects of TIBO derivatives on different strains of
      simian immunodeficiency virus.
AB  - Recently, several classes of compounds have been shown to be extremely selective
      inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in vitro.
      These include the tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-one and 
      thione (TIBO), 1-(2-hydroxyethoxymethyl)-6-(phenylthio)-thymine (HEPT),
      dipyridodiazepinone, pyridinone and bis(heteroaryl)piperazine derivatives. The
      hallmark of these new antiviral compounds is a specific interaction with reverse
      transcriptase (RT) of HIV-1. They are inactive against HIV-2 and any other
      viruses tested. Here we describe that, in addition to the HIV-1 strains, two
      simian immunodeficiency virus (SIV) strains from African green monkeys (SIVagm3
      and SIVagmTYO-1) are also sensitive to the TIBO class of compounds. TIBO and HEPT
      derivatives block the replication of SIVagm in cell culture at micromolar
      concentrations. Kinetics of inhibition of SIVagm RT by TIBO are competitive with
      respect to the natural substrate (dGTP). Amino acid alignments and site-directed
      mutagenesis point to the critical role of amino acid residues Y181 and Y188 in
      the sensitivity of HIV-1 RT and SIVagm RT to inhibition by the TIBO derivatives.
      Antiviral efficacy studies with this range of compounds and using sensitive SIV
      strains are now feasible in monkeys.

PMID- 1378482
TI  - Prevalence of anti-HCV and HCV viremia in hemodialysis patients in Taiwan.
AB  - Hepatitis C viral infection in 125 hemodialysis patients from Taiwan was studied
      using a second-generation anti-HCV immunoassay (EIA II) (Abbott HCV 2.0 EIA) and
      the polymerase chain reaction (PCR) to detect the HCV RNA in the serum. A total
      of 59 patients (47.2%) were positive by EIA II. In comparison, the conventional
      C100-3 anti-HCV assay was positive in 40 (32.0%). HCV RNA was found in 47
      patients (37.6%). Patients with elevated serum transaminase level had a higher
      positive rate of anti-HCV and HCV RNA. The dialysis time was longer for those
      patients positive for anti-HCV than for those who were negative. A total of 57 of
      the 59 EIA II-positive cases had a history of blood transfusion. The HBsAg status
      did not influence the anti-HCV positivity. Among the 59 EIA II-positive patients,
      66.1% were also positive for HCV RNA, and of the 47 HCV RNA-positive cases 83.0%
      were positive for EIA II. It is concluded that the high prevalence of specific
      HCV infection and HCV viremia was present in these patients. Prevention of cross
      contamination during dialysis and blood screening before transfusion are
      important for the control of HCV infection in these patients.

PMID- 1378483
TI  - Seroprevalence of hepatitis C antibody in Peru.
AB  - The prevalence in Peru of antibody to hepatitis C virus (anti-HCV) was determined
      in a survey of populations living in the northern jungle region and in groups at
      high risk of parenterally and sexually transmitted diseases. All sera were
      initially screened for anti-HCV using commercial first and second generation
      ELISAs; repeatedly reactive sera were further verified with a second generation
      immunoblot assay. Serum samples were also tested by ELISA for HBsAg, anti-HBs,
      and anti-HBc. None of 2,111 sera obtained in the survey of jungle residents was
      positive for anti-HCV by immunoblot assay. Twelve of 16 HIV-1 antibody positive
      hemophiliacs, one of 103 HIV-1 antibody positive homosexuals, and three of 602
      HIV-1 negative registered female prostitutes were positive for anti-HCV. A high
      prevalence of total markers of hepatitis B infection was found in all subjects,
      especially in older subjects and groups at high risk of parenterally and sexually
      transmitted diseases. The findings of this study indicate that seropositivity for
      hepatitis C virus antibody is uncommon in Peru except in high risk groups and
      suggest that the epidemiology of hepatitis C differs substantially from hepatitis
      B.

PMID- 1378484
TI  - Prevalence of hepatitis C virus antibodies and hepatitis C virus-RNA in an urban
      population.
AB  - Several studies had been carried out on anti-hepatitis C virus (HCV) prevalence
      in populations with blood exposure risks and in blood donors. New tests are now
      available which allow the investigation to extend to other parameters such as
      antibody type and HCV-RNA. In this study the prevalence of anti-HCV c100-3 and
      the associated epidemiological, clinical, and virological markers were evaluated
      in subjects from an urban population located in central Italy. In positive cases
      the time persistence of HCV-RNA and anti-HCV antibody pattern was studied. For
      this purpose, sera from 1,484 randomly sampled individuals, aged 30-69 years,
      collected in 1985 and stored at -80 degrees C were retrospectively tested. The
      prevalence was 0.87% (i.e., 13 anti-HCV c100-3 positive cases). A significant
      association was observed with raised alanine transaminase (ALT) levels (P less
      than 0.001). Paired serum samples from 11 out of the 13 subjects collected in
      1985 and 1991 were tested by nested polymerase chain reaction (PCR) using primers
      from the 5' non-coding region and by 4-RIBA. Concordant RIBA patterns between
      1985 and 1991 were observed in the majority of positive paired sera (7/9) as well
      as for HCV-RNA (6/9). HCV-RNA was present in sera simultaneously positive to both
      types of antibody or to anti-c100-3 or anti-c22 alone. A wide spectrum of viral
      and antibody patterns in anti-HCV c100-3 positive sera was observed in this urban
      population and persisted for at least 6 years.

PMID- 1378486
TI  - Preincubation with substance P induces substance P-stimulated
      phosphatidylinositol turnover in cultured cerebellar astrocytes.
AB  - In this study we have investigated the effects of preincubation of cultured
      astrocytes with substance P (SP) on subsequent 125I-Bolton-Hunter conjugated SP
      (125I-BHSP) receptor binding, and SP-stimulated phosphatidyl-inositol (PI)
      accumulation. Spinal cord astrocytes preincubated for up to 96 h with SP (0.001
      1,000 nM) suffered a dose-dependent decrease in both subsequent 125I-BHSP and SP
      stimulated PI turnover. In contrast, preincubation of cerebellar astrocytes with
      SP resulted in an increase in SP-stimulated PI turnover, with no change in 125I
      BHSP receptor binding. SP-induced PI turnover in cerebellar astrocytes was
      maximal after 72 h of preincubation with 0.1 nM SP. These data suggest that
      increased coupling between receptor and second messenger occurs in response to
      chronic exposure to SP.

PMID- 1378485
TI  - Tachykinin-stimulated inositol phospholipid hydrolysis and taurine release from
      human astrocytoma cells.
AB  - The activation of NK1 receptors on U373 MG human astrocytoma cells by substance P
      (SP) and related tachykinins was accompanied by an increase in taurine release
      and an accumulation of inositol phosphates. Both of these effects could be
      inhibited by spantide, a SP receptor antagonist. The relative potency of
      tachykinins in stimulating 3H-inositol phosphate accumulation correlated very
      well with their effects in stimulating the release of [3H]-taurine and inhibition
      125I-Bolton-Hunter reagent-conjugated SP binding. The effect on [3H]taurine
      release was mimicked by a protein kinase C (PKC) activator, phorbol 12-myristate
      13-acetate (PMA). The inactive phorbol ester analogue 4-alpha-phorbol 12,13
      didecanoate, however, was without effect. Both SP- and PMA-induced releases of
      [3H]-taurine were markedly inhibited by staurosporine, a potent PKC inhibitor.
      Pretreatment of U373 MG cells with 10 microM PMA for 19 h to down-regulate PKC
      activity also markedly inhibited both SP- and PMA-induced releases of [3H]
      taurine. Treatment of cells with 100 nM SP induced a time-dependent translocation
      of PKC from the cytosolic fraction to the membrane fraction. These findings are
      consistent with the hypothesis that an activation of NK1 receptors on U373 MG
      cells results in the release of inositol phosphates and activation of PKC, which
      in turn may regulate the release of taurine.

PMID- 1378487
TI  - Differential modulation by divalent cations of [3H]MK-801 binding in brain
      synaptic membranes.
AB  - Endogenous divalent cations, such as Mg2+, Ca2+, and Zn2+, differentially
      affected the binding of (+)-[3H]5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,10-imi ne maleate ([3H]MK-801) to an ion channel associated with an N-methyl-D
      aspartate-sensitive subclass of excitatory amino acid receptors in different
      preparations of brain synaptic membranes. Both Mg2+ and Ca2+ were weak inhibitors
      of the binding in membranes which had not been extensively washed (nonwashed
      membranes), over a concentration range effective in markedly potentiating the
      binding in the absence of any added stimulants in membranes which had been
      extensively washed, but not treated with a detergent (untreated membranes). In
      membranes extensively washed and treated with Triton X-100 (Triton-treated
      membranes), both cations significantly potentiated the binding in the presence of
      added glutamate alone. In contrast, Zn2+ was invariably active as a potent
      inhibitor of the binding irrespective of the membrane preparations used. In
      untreated membranes, Ca2+ markedly accelerated the initial association rate of
      [3H]MK-801 binding without affecting the binding at equilibrium in a manner
      similar to that found with glycine, as well as with glutamate; Mg2+, however,
      facilitated the initial association rate with a concomitant reduction of the
      binding at equilibrium. Zn2+ was effective in accelerating the initial rapid
      phase of association, with the initial slow phase being delayed, and in markedly
      reducing the binding at equilibrium. Both Mg2+ and Ca2+ also facilitated
      dissociation of the bound [3H]MK-801 and Zn2+ slowed the dissociation in
      untreated membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378488
TI  - Binding properties of 3-[125I]iodophencyclidine, a new radioligand for N-methyl-D
      aspartate-gated ionic channels.
AB  - The binding properties of the 125I-labeled phencyclidine derivative N-[1-(3
      [125I]iodophenyl)cyclohexyl]piperidine (3-[125I]iodo-PCP), a new ligand of the N
      methyl-D-aspartate (NMDA)-gated ionic channel, were investigated. Association and
      dissociation kinetic curves of 3-[125I]iodo-PCP with rat brain homogenates were
      well described by two components. About 32% of the binding was of fast
      association and fast dissociation, and the remaining binding was of slow
      association and slow dissociation. Saturation curves of 3-[125I]iodo-PCP also
      were well described using two binding sites: one of a high affinity (KDH = 15.8
      +/- 2.3 nM) and the other of a low affinity (KDL = 250 +/- 40 nM). 3-Iodo-PCP
      inhibited the binding of 3-[125I]iodo-PCP with inhibition curves that were well
      fitted by a two-site model. The binding constants (KiH, BmaxH; KiL, BmaxL) so
      obtained were close to those obtained in saturation experiments. Ligands of NMDA
      gated ionic channels also inhibited the binding of 3-[125I]iodo-PCP with two
      constants, KiH and KiL. There was a very good correlation (r = 0.987) between the
      affinities of these ligands to bind to NMDA-gated ionic channels and their
      potencies to inhibit the binding of 3-[125I]iodo-PCP with a high affinity.
      Moreover, the regional distribution of the high-affinity binding of 3-[125I]-iodo
      PCP paralleled that of tritiated N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP).
      In contrast to that of [3H] TCP, the binding of 3-[125I]iodo-PCP to well-washed
      rat brain membranes was fast and insensitive to glutamate and glycine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1378489
TI  - Activation of protein kinase C in permeabilized human neuroblastoma SH-SY5Y
      cells.
AB  - The activation of protein kinase C was investigated in digitonin-permeabilized
      human neuroblastoma SH-SY5Y cells by measuring the phosphorylation of the
      specific protein kinase C substrate myelin basic protein4-14. The phosphorylation
      was inhibited by the protein kinase C inhibitory peptide PKC19-36 and was
      associated to a translocation of the enzyme to the membrane fractions of the SH
      SY5Y cells. 1,2-Dioctanoyl-sn-glycerol had no effect on protein kinase C activity
      unless the calcium concentration was raised to concentrations found in stimulated
      cells (above 100 nM). Calcium in the absence of other activators did not
      stimulate protein kinase C. Phorbol 12-myristate 13-acetate was not dependent on
      calcium for the activation or the translocation of protein kinase C. The induced
      activation was sustained for 10 min, and thereafter only a small net
      phosphorylation of the substrate could be detected. Calcium or
      dioctanoylglycerol, when applied alone, only caused a minor translocation,
      whereas in combination a marked translocation was observed. Arachidonic acid (10
      microM) enhanced protein kinase C activity in the presence of submaximal
      concentrations of calcium and dioctanoylglycerol. Quinacrine and p-bromophenacyl
      bromide did not inhibit calcium- and dioctanoylglycerol-induced protein kinase C
      activity at concentrations which are considered to be sufficient for
      phospholipase A2 inhibition.

PMID- 1378490
TI  - Maitotoxin-induced intracellular calcium rise in PC12 cells: involvement of
      dihydropyridine-sensitive and omega-conotoxin-sensitive calcium channels and
      phosphoinositide breakdown.
AB  - The biological activities of maitotoxin are strictly dependent on the
      extracellular calcium concentration and are always associated with an increase of
      the free cytosolic calcium level. We tested the effects of voltage-sensitive
      calcium channel blockers (nicardipine and omega-conotoxin) on maitotoxin-induced
      intracellular calcium increase, membrane depolarization, and inositol phosphate
      production in PC12 cells. Maitotoxin dose dependently increased the cytosolic
      calcium level, as measured by the fluorescent probe fura 2. This effect
      disappeared in a calcium-free medium; it was still observed in the absence of
      extracellular sodium and was enhanced by the dihydropyridine calcium agonist Bay
      K 8644. Nicardipine inhibited the effect of maitotoxin on intracellular calcium
      concentration in a dose-dependent manner. The maitotoxin-induced calcium rise was
      also reduced by pretreating cells with omega-conotoxin. Pretreatment of cells
      with maitotoxin did not modify 125I-omega-conotoxin and [3H]PN 200-110 binding to
      PC12 membranes. Nicardipine and omega-conotoxin inhibition of maitotoxin-evoked
      calcium increase was reduced by pertussis toxin pretreatment. Maitotoxin caused a
      substantial membrane depolarization of PC12 cells as assessed by the fluorescent
      dye bisoxonol. This effect was reduced by pretreating the cells with either
      nicardipine or omega-conotoxin and was almost completely abolished by the
      simultaneous pretreatment with both calcium antagonists. Maitotoxin stimulated
      inositol phosphate production in a dose-dependent manner. This effect was reduced
      by pretreating the cells with 1 microM nicardipine and was completely abolished
      in a calcium-free EGTA-containing medium. The findings on maitotoxin-induced
      cytosolic calcium rise and membrane depolarization suggest that maitotoxin exerts
      its action primarily through the activation of voltage-sensitive calcium
      channels, the increase of inositol phosphate production likely being an effect
      dependent on calcium influx. The ability of nicardipine and omega-conotoxin to
      inhibit the effect of maitotoxin on both calcium homeostasis and membrane
      potential suggests that L- and N-type calcium channel activation is responsible
      for the influx of calcium following exposure to maitotoxin, and not that a
      depolarization of unknown nature causes the opening of calcium channels.

PMID- 1378492
TI  - In vivo monitoring of uric acid with chronically implanted probes.

PMID- 1378491
TI  - Transsynaptic regulation of galanin, neurotensin, and substance P in the adrenal
      medulla: combinatorial control by second-messenger signaling pathways.
AB  - The adrenomedullary content of neurotensin and substance P was examined 1, 6, and
      12 days after hypoglycemic shock. The neurotensin content was increased 60-fold
      within 24 h and remained elevated for up to 12 days, whereas the substance P
      content was increased approximately sevenfold within 24 h of insulin treatment
      and returned to control levels by 12 days poststimulation. Because protein kinase
      A, protein kinase C, and calcium influx in the rat adrenal medulla are all
      stimulated following splanchnic nerve stimulation, the differential regulation of
      neurotensin and substance P biosynthesis following stimulation of these three
      pathways was examined in bovine chromaffin cells in vitro. Neurotensin levels
      were up-regulated by elevated potassium, forskolin, and phorbol ester in bovine
      chromaffin cells. Substance P levels were up-regulated by elevated potassium and
      forskolin but not by phorbol ester treatment. When chromaffin cells were treated
      with phorbol ester in combination with forskolin, neurotensin levels were
      increased in a synergistic fashion, whereas phorbol ester antagonized the
      forskolin-induced elevation of substance P levels. Earlier, it was reported that
      galanin biosynthesis, like neurotensin biosynthesis, is upregulated by
      depolarization, phorbol ester stimulation, and forskolin treatment in chromaffin
      cells in vitro. Here we report that galanin is also, like neurotensin, increased
      greater than 60-fold after stimulation of the rat adrenal medulla in vivo.
      Neuropeptide-specific combinatorial effects of stimulating the calcium, protein
      kinase A, and protein kinase C signaling pathways may underlie the quantitative
      differences between galanin and neurotensin compared with substance P up
      regulation in rat adrenal medulla after splanchnic nerve stimulation in vivo.

PMID- 1378493
TI  - The effect of moderate haemodilution with Fluosol-DA or Hespan on the
      nonmicrosomal acetylation of sulphadimidine in the rat.
AB  - The effects of Fluosol-DA (Fluosol) and Hespan haemodilution on the nonmicrosomal
      acetylation of sulphadimidine were studied in male rats. Fluosol increased the
      acetylsulphadimidine percent excreted in urine, the metabolic formation rate
      constant (kf), and the formation clearance (CLF) for 72 h after haemodilution
      without any significant changes in the sulphadimidine apparent volume of
      distribution (Vd) or total body clearance (CL). Hespan haemodilution increased
      the acetylsulphadimidine percent excreted in urine only at 48 h while
      significantly decreasing the sulphadimidine clearance, urinary excretion rate
      constant (ku), and renal clearance (CLR) for 72 h. The enhanced N
      acetyltransferase activity after Fluosol haemodilution may have therapeutic
      consequences for concomitantly given drugs metabolized by this enzyme.

PMID- 1378494
TI  - Microvascular salvage procedures with adjuvant antithrombotic therapy for
      restitution of patency in a rat model.
AB  - Thrombosis following microvascular anastomosis requires further surgical
      intervention, involving anastomotic resection and reanastomosis or
      interpositional vein grafting. This study was undertaken to investigate different
      methods of salvaging thrombosed vessels, using a rat-vein model of error-induced
      thrombosis. Vessels were reconstructed 4 hr after the onset of thrombosis, using
      one of three methods: Group 1--removal of the erroneously placed stitch; Group 2-
      anastomotic resection and re-anastomosis; and Group 3--resection and replacement
      with a vein graft. Adjuvant antithrombotic therapy was simultaneously evaluated,
      assessing the influence of systemic Iloprost or heparin. Patency rates at one day
      postoperatively were 0 percent, 12.5 percent and 37.5 percent for Groups 1, 2,
      and 3, respectively. Following Iloprost infusion, these rates increased to 25
      percent, 25 percent, and 56.3 percent, respectively and, following heparin
      administration, to 50 percent, 68.8 percent, and 81.8 percent, respectively.
      Significant increases were found for vein grafting (Group 3), and for the heparin
      treated subgroups using all three methods. Effective levels of both Iloprost and
      heparin were confirmed by increases noted in rat-tail bleeding times. Significant
      rates of recanalization by three days following one-day occlusion were found in
      Groups 1 and 2. These results support the application of vein-graft replacement
      for thrombosed veins, concurrently with systemic heparinization. This study
      further confirms the high rate of recanalization seen in thrombosed rat femoral
      veins.

PMID- 1378495
TI  - Phenotypic analysis of peripheral blood monocytes isolated from patients with
      rheumatoid arthritis.
AB  - The expression of CD14, Fc gamma receptor I (Fc gamma RI), Fc gamma RII, and HLA
      DR on peripheral blood monocytes from patients with rheumatoid arthritis (RA) was
      studied to investigate their nature and their role in the pathogenesis of
      rheumatoid synovitis. Peripheral blood mononuclear cells obtained from 9 patients
      with active RA, 8 patients with RA in complete remission, and 14 healthy
      individuals, were stained with various monoclonal antibodies and analyzed on a
      fluorescence activated cell sorter. The expression of CD14 as well as Fc gamma RI
      and Fc gamma RII was upregulated on peripheral blood monocytes from patients with
      active RA, although the expression of HLA-DR was not increased. In addition, the
      expression of Fc gamma RI and Fc gamma RII on monocytes was still upregulated in
      patients with RA in complete remission, whereas the expression of CD14 on
      monocytes was normalized in these patients. These results indicate that
      peripheral blood monocytes in patients with active RA are already activated to
      express higher densities of CD14. In addition, our observation that CD14 density
      was increased on a subset of circulating blood monocytes in active RA, that HLA
      DR was not significantly altered and that Fc gamma RI and Fc gamma RII were
      increased in both active and inactive RA is not compatible with the expected
      actions of interferon gamma. Finally, it is suggested that peripheral blood
      monocytes in patients with RA may have intrinsic abnormalities as evidenced by
      the enhanced expression of Fc gamma R, which is repeatedly observed regardless of
      the disease activity of RA.

PMID- 1378497
TI  - Scleroderma in association with the use of bleomycin: a report of 3 cases.
AB  - Although an association between exposure to bleomycin and the development of
      scleroderma has been suspected, few cases are reported. We describe the
      development of cutaneous scleroderma in 3 patients coincident with the use of
      bleomycin in low cumulative doses of less than 100 U. Dramatic clinical
      improvement occurred in 2 patients treated with high dose steroids. Our series of
      3 patients supports a causal connection between bleomycin and scleroderma. In
      light of the widespread use of bleomycin, this complication may be under
      appreciated.

PMID- 1378496
TI  - Rheumatoid arthritis serum or synovial fluid and interleukin 2 abnormally expand
      natural killer-like cells that are potent stimulators of IgM rheumatoid factor.
AB  - We show that rheumatoid arthritis (RA) serum or synovial fluid (SF) increases the
      growth capacity of normal, interleukin 2 (IL-2) driven cell preparations,
      compared to normal human serum (NHS). Proliferation in RA serum and SF cultures
      was primarily associated with expansion of natural killer (NK)-like cells (CD16+,
      CD57+), and in NHS cultures, with T cell (CD3+ CD4+ CD8+) growth. The capacity of
      RA serum to promote NK cell growth was related to patient global clinical
      activity and rheumatoid factor (RF) titers. The NK-like cells, but not the T-like
      cells, induced high levels of IgM RF synthesis in autologous B cells. Thus,
      alteration in NK cell growth may disrupt NK-B cell circuits in RA and contribute
      to B cell dysfunction (RF synthesis).

PMID- 1378498
TI  - The importance of combining xylene clearance and immunohistochemistry in the
      accurate staging of colorectal carcinoma.
AB  - The prognosis of colorectal carcinoma relies heavily on pathological staging
      which includes the metastatic state of lymph nodes. Colorectal resectates from 47
      patients (41 with colorectal carcinoma and six with non-malignant disease) were
      entered into a study to assess the best method for detecting metastases in lymph
      nodes. The maximum number of lymph nodes was harvested at an initial careful
      examination of the specimen. Subsequently, the pericolic and perirectal fat was
      dissected out, dehydrated in alcohol, cleared in xylene and further lymph nodes
      were recovered. Both sets of lymph nodes were examined by the standard
      histological method and subsequently stained immunohistochemically for
      cytokeratins (CK). The mean number of lymph nodes recovered at the initial
      dissection from all 47 cases was 6.7, this was raised to 58.2 after xylene
      clearance, ie an average of 51.5 lymph nodes were not recovered by traditional
      methods. At the initial dissection no epithelial cells were detected in any of
      the lymph nodes from the nonmalignant cases or 25 of the malignant cases. In the
      other 16 cases, epithelial cells were detected by H&E in 38 lymph nodes. Thus the
      initial staging was 3 Dukes A, 22 Dukes B and 16 Dukes C. After
      immunohistochemistry, eight additional cases (originally staged Dukes B) showed
      epithelial cells in the lymph nodes, these were chiefly occult invasion, raising
      the involved lymph nodes number to 70. After xylene clearance and applying the CK
      staining, an additional 135 lymph nodes were found to be involved, thus the
      overall number of involved lymph nodes was increased to 205. The combined
      technique changed the Dukes staging in 12 out of 41 cases of colorectal
      carcinoma, resulting finally in 3 Dukes A, 10 Dukes B and 28 Dukes C, ie 55% of
      Dukes B become Dukes C.

PMID- 1378499
TI  - Protection conferred on mice by combinations of monoclonal antibodies directed
      against outer-membrane proteins or smooth lipopolysaccharide of Brucella.
AB  - The effect of monoclonal antibodies (MAbs) injected alone or in combination on
      brucella splenic infection in CD-1 mice was tested 7 and 21 days after a
      challenge with virulent Brucella abortus 544. Passive immunisation of mice with
      anti-25-27-kDa MAb alone, or mixed with protective anti-16.5 and anti-36-38-kDa
      MAbs, or with MAbs of the same specificity which were previously demonstrated to
      have no activity on CD-1 mice, produced a significant reduction of spleen counts
      of B. abortus (p less than 0.01). Other combinations of MAbs did not reduce
      splenic infection in comparison with the untreated control group. BALB/c mice
      were used to test the possible interference of the immune response of CD-1 mice
      against MAbs that were produced in BALB/c mice. No reduction of splenic infection
      was shown with anti-25-27- or -36-38-kDa MAbs, whereas anti-lipopolysaccharide
      (LPS) MAb which was produced in CBA mice was effective. Combination of anti
      protein MAbs with the anti-LPS MAb produced only the effect of the anti-LPS MAb
      at 7 and 21 days after challenge.

PMID- 1378500
TI  - Activation of K+ and Cl- channels in MDCK cells during volume regulation in
      hypotonic media.
AB  - Single-channel patch-clamp experiments were performed on MDCK cells in order to
      characterize the ionic channels participating in regulatory volume decrease
      (RVD). Subconfluent layers of cultured cells were exposed to a hypotonic medium
      (150 mOsm), and the membrane currents at the single-channel level were measured
      in cell-attached experiments. The results indicate that MDCK cells respond to a
      hypotonic swelling by activating several different ionic conductances. In
      particular, a potassium and a chloride channel appeared in the recordings more
      frequently than other channels, and this allowed a more detailed study of their
      properties in the inside-out configuration of the patch-clamp technique. The
      potassium channel had a linear I/V curve with a unitary conductance of 24 +/- 4
      pS in symmetrical K+ concentrations (145 mM). It was highly selective for K+ ions
      vs. Na+ ions: PNa/PK less than 0.04. The time course of its open probability (P0)
      showed that the cells responded to the hypotonic shock with a rapid activation of
      this channel. This state of high activity was maintained during the first minute
      of hypotonicity. The chloride channel participating in RVD was an outward
      rectifying channel: outward slope conductance of 63.3 +/- 4.7 pS and inward slope
      conductance of 26.1 +/- 4.9 pS. It was permeable to both Cl- and NO3- and its
      maximal activation after the hypotonic shock was reached after several seconds
      (between 30 and 100 sec). The activity of this anionic channel did not depend on
      cytoplasmic calcium concentration. Quinine acted as a rapid blocker of both
      channels when applied to the cytoplasmic side of the membrane. In both cases, 1
      mM quinine reversibly reduced single-channel current amplitudes by 20 to 30%.
      These results indicate that MDCK cells responded to a hypotonic swelling by an
      early activation of highly selective potassium conductances and a delayed
      activation of anionic conductances. These data are in good agreement with the
      changes of membrane potential measured during RVD.

PMID- 1378501
TI  - Dimerization constant and single-channel conductance of gramicidin in thylakoid
      membranes.
AB  - The effect of the pore-forming antibiotic gramicidin on pure lipid membranes is
      well characterized. We studied its action in protein-rich thylakoid membranes
      that contain less than 25% (wt/wt) acyl lipids. A transmembrane voltage was
      induced by flashing light, and its decay was measured and interpreted to yield
      the distribution of gramicidin over thylakoids, its dimerization constant and its
      single-channel conductance in this membrane. The distribution of gramicidin over
      the ensemble of thylakoids was immediately homogeneous when the antibiotic was
      added under stirring, while it became homogeneous only after 20 min in a stirred
      suspension that was initially heterogeneous. The dimerization constant, 5 x
      10(14) cm2/mol, was about 10 times larger than in pure lipid membranes. This was
      attributed to the up-concentration of gramicidin in the small fractional area of
      protein-free lipid bilayer and further by a preference of gramicidin for stacked
      portions of the membrane. The latter bears important consequences with regard to
      bioenergetic studies with this ionophore. As gramicidin was largely dimerized
      from a concentration of 1 nM (in the suspension) on, the membrane's conductance
      then increased linearly as a function of added gramicidin. When the negative
      surface potential at the thylakoid membrane was screened, the conductance of a
      single gramicidin dimer agreed well with figures reported for bilayers from
      neutral lipid (about 0.5 pS at 10 mM NaCl). The modulation of the conductance by
      the surface potential in spinach versus pea thylakoids and between different
      preparations is discussed in detail.

PMID- 1378503
TI  - Dystrophin immunoreactivity in normal and Duchenne human fetal neurons in
      culture.
AB  - Dystrophin, the protein product defective in Duchenne muscular dystrophy (DMD),
      is present in all types of muscle and in the brain. The function of the protein
      is unknown and its role in the brain is unclear, although 30% of DMD patients
      show nonprogressive mental retardation. We have therefore studied the
      localisation of dystrophin in cultures of normal and DMD human fetal neurons
      using antibodies raised to different regions of the protein. Dystrophin
      immunoreactivity was demonstrated in the soma and axon hillock of normal neurons
      and appeared to be associated with the inner part of the cell membrane, although
      some intracellular staining was also observed. Positive dystrophin staining was
      present only in cells with fully developed neuronal features, although not all
      the neurons were positive. Glial cells were always negative for the antigen.
      Immunostaining with antibodies to the brain spectrins indicate that the
      dystrophin antibodies did not crossreact with these proteins. The possibility of
      cross-reactivity with other proteins is discussed. Studies of cells cultured from
      a DMD fetus also showed specific dystrophin immunostaining in neurons, although
      the muscle was generally negative for dystrophin. However, the localisation of
      dystrophin immunostaining and that of the brain spectrins and neurofilaments
      appeared abnormal, as did the overall morphology of the cells. This suggests that
      dystrophin may play a role during brain development and dystrophin deficiency
      results in abnormal neuronal features. This would be consistent with the
      nonprogressive nature of the mental retardation observed in DMD patients.

PMID- 1378504
TI  - Light and electron microscopic localization of B-50 (GAP43) in the rat spinal
      cord during transganglionic degenerative atrophy and regeneration.
AB  - Crush or transection of a peripheral nerve is known to induce transganglionic
      degenerative atrophy (TDA) in the segmentally related, ipsilateral Rolando
      substance of the spinal cord. When the lost peripheral connectivity is
      reestablished, the consecutive regenerative synaptoneogenesis results in
      restoration of the circuitry in the formerly deteriorated upper dorsal horn.
      Enhanced expression of the growth-associated protein (GAP43) B-50 occurs during
      neuronal differentiation, axon outgrowth, and peripheral nerve regeneration. This
      study documents changes in immunocytochemical distribution of B-50 in the regions
      of the lumbar spinal cord which are segmentally related to the axotomized sciatic
      nerve. At the light microscopic level, a weak B-50 immunoreactivity (BIR) is
      present in the neuropil of the upper dorsal horn of control animals. After
      unilateral transection and ligation of the sciatic nerve, BIR increased in the
      ipsilateral upper dorsal horn at 17 days postinjury, but decreased again after 24
      days with respect to the contralateral side. Differences between effects of crush
      and transection were prominent in combined crush-cut experiments as well (i.e.,
      after unilateral crush and contralateral transection and ligation of the sciatic
      nerve). Electron microscopic studies show that in the uninjured and injured
      spinal cord, BIR is detected in axons and axon terminals, but not all are
      stained. After transection of the sciatic nerve, BIR is found in afflicted
      primary sensory axon terminals, including those contacting substantia gelatinosa
      neurons and in axon terminals undergoing glial phagocytosis. The localization of
      BIR seen after crushing the sciatic nerve is similar. However, at 24 days after
      crush, BIR is detected also in axonal growth cones. In the ventral horn of
      control animals, synaptic boutons impinging upon motor neurons exhibited weak
      BIR. At 17 days after unilateral transection of the sciatic nerve, the
      pericellular BIR surrounding motor neurons is decreased at the ipsilateral with
      respect to the contralateral side, whereas 24 days after crush injury it
      increased considerably. Our results show that peripheral nerve injury inducing
      TDA also affects BIR distribution in the spinal gray matter. Successful
      regeneration of the peripheral nerve after crush lesion is associated with
      enhanced expression of B-50 in growth cones of sprouting central axons. The
      neuroplastic response of B-50 is in line with a function of B-50 in axonal
      sprouting and reactive synaptogenesis.

PMID- 1378502
TI  - Metastatic model for human prostate cancer using orthotopic implantation in nude
      mice.
AB  - BACKGROUND: Understanding the mechanism of prostate cancer metastasis is
      essential to the design of a more effective therapy. An effective therapy for
      this disease will depend on the development of a clinically relevant in vivo
      model. PURPOSE: We describe the development of such a model by using orthotopic
      implantation of human prostate cells in BALB/c nude mice. METHOD: We compared the
      tumorigenicity of and the incidence of metastasis of human prostate cancer PC-3M
      and LNCaP-FGC (LNCaP) cell lines subsequent to prostatic (orthotopic) or
      subcutaneous (ectopic) implantations in male nude mice. RESULTS: LNCaP cells
      produced tumors only in the prostate. Enhanced tumorigenicity at the orthotopic
      site was found for PC-3M cells. Lymph node metastases were observed in
      practically all mice given an injection of PC-3M cells in the prostate, but they
      were uncommon with subcutaneous injection of these cells. Bilateral orchiectomy
      did not alter the tumorigenicity of either PC-3M or LNCaP cells or the incidence
      of lymph node metastasis by PC-3M cells. LNCaP tumors in the mouse prostate (but
      not PC-3M tumors) elaborated detectable levels of human prostate-specific antigen
      (PSA) in the serum, even when tumors were small (1.5 mm in diameter).
      Immunohistochemistry analysis revealed the presence of the PSA marker in tissue
      sections of LNCaP but not of PC-3M tumors. CONCLUSIONS: The implantation of human
      prostate cancer cells in an ectopic environment does not permit expression of
      metastatic potential. In contrast, intraprostatic implantation does.
      IMPLICATIONS: These data suggest that the orthotopic injection of human prostate
      cancer cells into the nude mouse may provide a valuable model to study the
      biology and therapy of human prostate cancer.

PMID- 1378505
TI  - Attenuation of influenza A virus by insertion of a foreign epitope into the
      neuraminidase.
AB  - As the initial step in generating a live attenuated influenza A vaccine, we
      attempted to substitute an unrelated amino acid sequence (FLAG) for a portion of
      the neuraminidase (NA) molecule in influenza virus A/WSN/33 (H1N1), using a
      recently developed technique (reverse genetics [W. Luytjes, M. Krystal, M. Enami,
      J. D. Parvin, and P. Palese, Cell 59:1107-1113, 1989]). This technique allowed us
      to rescue the NA molecules containing the FLAG sequence (Asp-Tyr-Lys-Asp-Asp-Asp
      Asp-Lys) at the bottom portion of the boxlike head of the molecule immediately
      above the stalk region (amino acid residues 63 to 70 [WSN NA numbering]). An anti
      FLAG monoclonal antibody immunoprecipitated the NA molecules with the FLAG
      sequence, demonstrating that the foreign epitope was exposed on the virion
      surface. The dose of FLAG-containing transfectant virus required to kill 50% of
      mice was 100-fold higher than the required dose of parent virus. The FLAG
      sequence was stably maintained in the NA molecule during passage of the virus in
      tissue culture and in mice. These findings demonstrate that live influenza A
      vaccine strains with stable attenuating mutations in the coding region of the
      viral genes can be generated by reverse genetics.

PMID- 1378506
TI  - Specificity of Rous sarcoma virus nucleocapsid protein in genomic RNA packaging.
AB  - Site-directed mutagenesis has shown that the nucleocapsid (NC) protein of Rous
      sarcoma virus (RSV) is required for packaging and dimerization of viral RNA.
      However, it has not been possible to demonstrate, in vivo or in vitro, specific
      binding of viral RNA sequences by NC. To determine whether specific packaging of
      viral RNA is mediated by NC in vivo, we have constructed RSV mutants carrying
      sequences of Moloney murine leukemia virus (MoMuLV). Either the NC coding region
      alone, the psi RNA packaging sequence, or both the NC and psi sequences of MoMuLV
      were substituted for the corresponding regions of a full-length RSV clone to
      yield chimeric plasmid pAPrcMNC, pAPrc psi M, or pAPrcM psi M, respectively. In
      addition, a mutant of RSV in which the NC is completely deleted was tested as a
      control. Upon transfection, each of the chimeric mutants produced viral particles
      containing processed core proteins but were noninfectious. Thus, MoMuLV NC can
      replace RSV NC functionally in the assembly and release of mature virions but not
      in infectivity. Surprisingly, the full-deletion mutant showed a strong block in
      virus release, suggesting that NC is involved in virus assembly. Mutant PrcMNC
      packaged 50- to 100-fold less RSV RNA than did the wild type; in cotransfection
      experiments, MoMuLV RNA was preferentially packaged. This result suggests that
      the specific recognition of viral RNA during virus assembly involves, at least in
      part, the NC protein.

PMID- 1378507
TI  - Coronavirus mRNA transcription: UV light transcriptional mapping studies suggest
      an early requirement for a genomic-length template.
AB  - Mouse hepatitis virus (MHV) synthesizes seven to eight mRNAs, each of which
      contains a leader RNA derived from the 5' end of the genome. To understand the
      mechanism of synthesis of these mRNAs, we studied how the synthesis of each mRNA
      was affected by UV irradiation at different time points after infection. When MHV
      infected cells were UV irradiated at a late time in infection (5 h
      postinfection), the syntheses of the various mRNAs were inhibited to different
      extents in proportion to the sizes of the mRNAs. Analysis of the UV inactivation
      kinetics revealed that the UV target size of each mRNA was equivalent to its own
      physical size. In contrast, when cells were irradiated at 2.5 or 3 h
      postinfection, there appeared to be two different kinetics of inhibition of mRNA
      synthesis: the synthesis of every mRNA was inhibited to the same extent by a
      small UV dose, but the remaining mRNA synthesis was inhibited by additional UV
      doses at different rates for different mRNAs in proportion to RNA size. The
      analysis of the UV inactivation kinetics indicated that the UV target sizes for
      the majority of mRNAs were equivalent to that of the genomic-size RNA early in
      the infection. These results suggest that MHV mRNA synthesis requires the
      presence of a genomic-length RNA template at least early in the infection. In
      contrast, later in the infection, the sizes of the templates used for mRNA
      synthesis were equivalent to the physical sizes of each mRNA. The possibility
      that the genomic-length RNA required early in the infection was used only for the
      synthesis of a polymerase rather than as a template for mRNA synthesis was ruled
      out by examining the UV sensitivity of a defective interfering (DI) RNA. We found
      that the UV target size for the DI RNA early in infection was much smaller than
      that for mRNAs 6 and 7, which are approximately equal to or smaller in size than
      the DI RNA. This result indicates that even though DI RNA and viral mRNAs are
      synthesized by the same polymerase, mRNAs are synthesized from a larger (genomic
      length) template. We conclude that a genomic-length RNA template is required for
      MHV subgenomic mRNA synthesis at least early in infection. Several transcription
      models are proposed.

PMID- 1378508
TI  - The interaction of two groups of murine genes determines the persistence of
      Theiler's virus in the central nervous system.
AB  - Theiler's murine encephalomyelitis virus is responsible for a chronic
      inflammatory demyelinating disease of the central nervous system of the mouse.
      The disease is associated with persistent viral infection of the spinal cord.
      Some strains of mice are susceptible to viral infection, and other strains are
      resistant. The effect of the genetic background of the host on viral persistence
      has not been thoroughly investigated. We studied the amount of viral RNA in the
      spinal cords of 17 inbred strains of mice and their F1 crosses with the SJL/J
      strain and observed a large degree of variability among strains. The pattern of
      viral persistence among mouse strains could be explained by the interaction of
      two loci. One locus is localized in the H-2D region of the major
      histocompatibility complex, whereas the other locus is outside this complex and
      is not linked to the Tcrb locus on chromosome 6.

PMID- 1378509
TI  - Activation of bovine leukemia virus transcription in lymphocytes from infected
      sheep: rapid transition through early to late gene expression.
AB  - Bovine leukemia virus (BLV) expression is mostly silent in peripheral blood
      mononuclear cells (PBMCs) of infected animals. However, when infected cells are
      cultured, they are stimulated to produce virus. We studied viral transcription in
      PBMCs taken from BLV-infected sheep because the pattern of transcriptional
      activation in these cells should closely mimic activation of virus expression
      within mononuclear cells in vivo. BLV transcription was activated as early as 30
      min after PBMCs were cultured. Expression was characterized by early and late
      stages, each distinguished by a unique pattern of cytoplasmic RNAs. In early
      expression, cytoplasmic viral RNA was exclusively the doubly spliced tax/rex
      transcript, although all transcripts were present in the nucleus. Early
      expression gave way rapidly to late expression, in which all viral transcripts
      accumulated in the cytoplasm. The polyclonal B-cell activator lipopolysaccharide
      increased the amount of viral RNA by at least twofold but did not alter the
      pattern of transcription. The transition from early to late expression required
      new protein synthesis and was blocked by the inhibitor cycloheximide. This
      requirement reflects the essential role of the viral Rex protein in the
      transition, but synthesis of cellular factors may be required as well. These
      results provide the first demonstration of staged viral expression in lymphocytes
      naturally infected by either BLV or the closely related human T-cell leukemia
      virus (HTLV) and validate the model of BLV and HTLV gene expression that
      previously was derived from transfection experiments performed mainly in
      nonlymphoid cells.

PMID- 1378510
TI  - A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational
      changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV
      1) and HIV-1 infection of CD4+ cells.
AB  - The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4,
      blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium
      formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J.
      Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we
      show that, in contrast to the CD4 domain 1 MAb 6H10, 5A8 and its Fab fragment do
      not block soluble CD4 (sCD4) binding to virions, whereas they do inhibit sCD4
      induced exposure of cryptic epitopes on gp41 and dissociation of gp120 from
      virions. Two other MAbs, OKT4 and L120, which are reactive with domains 3 and 4
      of CD4, have little or no effect on HIV-1 infection, syncytium formation, or sCD4
      induced conformational changes in the envelope glycoproteins. The mechanisms of
      action of 5A8 and 6H10 can be further distinguished in syncytium inhibition
      assays: 6H10 blocks competitively, while 5A8 does not. We opine that 5A8 blocks
      HIV-1 infection and fusion by interfering with conformational changes in
      gp120/gp41 and/or CD4 that are necessary for virus-cell fusion.

PMID- 1378511
TI  - Galactosyl ceramide (or a closely related molecule) is the receptor for human
      immunodeficiency virus type 1 on human colon epithelial HT29 cells.
AB  - The gastrointestinal tract is considered to be a major route of infection for
      human immunodeficiency virus (HIV). Infection of human colon epithelial cells by
      HIV is not blocked by anti-CD4 antibodies known to block infection of lymphoid
      cells (J. Fantini, N. Yahi, and J. C. Chermann, Proc. Natl. Acad. Sci. USA
      88:9297-9301, 1991), suggesting the presence of an alternate receptor for HIV on
      these cells. In this report, we show that (i) a monoclonal antibody specifically
      directed against galactosyl ceramide inhibited the infection of HT29 cells by two
      markedly different strains of HIV-1, as assessed by polymerase chain reaction
      amplification and reverse transcriptase assay; (ii) this antibody strongly
      labeled the surface of HT29 cells by immunofluorescence and electron microscopic
      immunolocalization; (iii) the labeling was preferentially but not totally
      restricted to the basolateral membrane domain of differentiated colonic cells, in
      agreement with the ability of HIV to infect both the apical and basolateral
      surfaces of these epithelial cells; and (iv) in thin-layer chromatography
      immunostaining experiments with neutral glycolipids prepared from HT29 cells, the
      antibody specifically reacted with a ceramide monoglycoside fraction
      corresponding to galactosyl ceramide. We did not detect this glycolipid in
      lymphoid cells, and anti-galactosyl ceramide antibodies consistently failed to
      inhibit HIV infection of these cells. These data suggest that galactosyl ceramide
      (or a derivative) is an essential component of the receptor for HIV on the
      surface of HT29 cells.

PMID- 1378513
TI  - Partial reverse transcripts in virions from human immunodeficiency and murine
      leukemia viruses.
AB  - Reverse transcription of the retroviral genome is thought to start after virions
      enter target cells. Purified preparations of human immunodeficiency virus were
      found to contain virus-specific DNA, detectable by polymerase chain reaction
      amplification. This DNA resulted from reverse transcription in newly assembled
      virus particles and not from contamination by cellular DNA, because virions
      contained a striking excess of early versus late transcripts and because the
      accumulation of these products was sensitive to 3'-azido-3'-deoxythymidine
      (zidovudine) treatment of producer cells. A similar observation was made with
      murine amphotropic retrovirus particles. It is therefore likely that all
      retroviruses contain partial reverse transcripts.

PMID- 1378514
TI  - Viral DNA carried by human immunodeficiency virus type 1 virions.
AB  - A fundamental step in the replication of retroviruses is the reverse
      transcription of the viral RNA genome into a double-stranded DNA provirus.
      Retroviruses are believed to carry genomic information only as RNA, and synthesis
      of DNA is thought to start only after virus entry into the infected cell. We
      report here that infectious mature human immunodeficiency virus type 1 virions
      contain viral DNA of heterogeneous size. This heterogeneity seems to result from
      random stops of reverse transcription during minus- and plus-strand synthesis.
      The DNA carried by human immunodeficiency virus type 1 virions presumably
      originates from reverse transcription which takes place prior to or during
      formation of the mature virus particle.

PMID- 1378512
TI  - Genetic analysis of type-specific antigenic determinants of herpes simplex virus
      glycoprotein C.
AB  - Herpes simplex virus type 1 (HSV-1) glycoprotein C (gC-1) elicits a largely
      serotype-specific immune response directed against previously described
      determinants designated antigenic sites I and II. To more precisely define these
      two immunodominant antigenic regions of gC-1 and to determine whether the
      homologous HSV-2 glycoprotein (gC-2) has similarly situated antigenic
      determinants, viral recombinants containing gC chimeric genes which join site I
      and site II of the two serotypes were constructed. The antigenic structure of the
      hybrid proteins encoded by these chimeric genes was studied by using gC-1- and gC
      2-specific monoclonal antibodies (MAbs) in radioimmunoprecipitation,
      neutralization, and flow cytometry assays. The results of these analyses showed
      that the reactivity patterns of the MAbs were consistent among the three assays,
      and on this basis, they could be categorized as recognizing type-specific
      epitopes within the C-terminal or N-terminal half of gC-1 or gC-2. All MAbs were
      able to bind to only one or the other of the two hybrid proteins, demonstrating
      that gC-2, like gC-1, contains at least two antigenic sites located in the two
      halves of the molecule and that the structures of the antigenic sites in both
      molecules are independent and rely on limited type-specific regions of the
      molecule to maintain epitope structure. To fine map amino acid residues which are
      recognized by site I type-specific MAbs, point mutations were introduced into
      site I of the gC-1 or gC-2 gene, which resulted in recombinant mutant
      glycoproteins containing one or several residues from the heterotypic serotype in
      an otherwise homotypic site I background. The recognition patterns of the MAbs
      for these mutant molecules demonstrated that (i) single amino acids are
      responsible for the type-specific nature of individual epitopes and (ii) epitopes
      are localized to regions of the molecule which contain both shared and unshared
      amino acids. Taken together, the data described herein established the existence
      of at least two distinct and structurally independent antigenic sites in gC-1 and
      gC-2 and identified subtle amino acid sequence differences which contribute to
      type specificity in antigenic site I of gC.

PMID- 1378515
TI  - Progression of early steps of human immunodeficiency virus type 1 replication in
      the presence of an inhibitor of viral protease.
AB  - We have evaluated a possible role for human immunodeficiency virus type 1
      protease during early steps of replication. For these studies, a specific
      inhibitor of human immunodeficiency virus protease, Ro31-8959, was used.
      Synthesis of viral cDNA, its integration into cellular DNA, and its transcription
      were determined during a one-step, acute infection of MT-4 cells. No consistent
      difference in any of these parameters was noted between control-infected cultures
      and those treated with protease inhibitor. However, no infectious progeny virus
      was produced in treated cultures, and thus spread of infection was severely
      restricted. Our results do not support an essential activity of viral protease in
      early steps of replication but are in line with its established role in gag and
      gag-pol processing and in maturation to infectious progeny virus.

PMID- 1378516
TI  - [Immunophenotypes and FAB classification].

PMID- 1378517
TI  - [The effects of cytokines on colony formation of human megakaryocytes].

PMID- 1378518
TI  - Release of endothelium-derived relaxing factor from resistance arteries in
      hypertension.
AB  - Aortic rings from SHR are reported to have a decreased relaxation response to the
      endothelium-dependent agent acetylcholine compared with rings from WKY rats.
      Thus, a reduced EDRF (nitric oxide) response could contribute to hypertension. We
      found that in mesenteric small resistance arteries (200 microns I.D.) taken from
      5- to 50-week old rats and mounted in a Mulvany-Halpern myograph, that the
      concentration-response curves to acetylcholine were similar in range and
      sensitivity (EC50) in arteries from SHR and WKY rats at the same age. Similarly,
      in small resistance arteries from human buttock skin, the relaxation to
      acetylcholine was not different between vessels from normotensive volunteers
      (mean BP = 95.2 +/- 1.5 mm Hg) and patients with untreated essential hypertension
      (mean BP = 116.5 +/- 2.5 mm Hg). In rabbits with chronic renovascular
      hypertension (cellophane renal wrap), acetylcholine and adenosine infusions into
      the lower abdominal aorta caused falls in hindquarter resistance that were
      enhanced in range, but with no change in sensitivity compared with normotensive
      rabbits. In normotensive rabbits, nitric oxide synthase inhibition with N omega
      nitro-L-arginine infusion caused a rise in blood pressure, fall in hindquarter
      conductance and blockade of the acetylcholine responses. These experiments
      suggest that at the level of resistance arteries in vivo and in vitro, a defect
      in the receptor-stimulated response to EDRF associated with hypertension could
      not be detected. Apparently, basal nitric oxide is important in resting
      vasodilator tone, but its role in chronic hypertension is still unclear.

PMID- 1378519
TI  - [Highlights on pain and suffering--report from a conference. The world of pain].

PMID- 1378520
TI  - Hospice care as an alternative to euthanasia.

PMID- 1378521
TI  - Expression of Alu and 7SL RNA in Alzheimer's and control brains.
AB  - We investigated whether changes in expression of RNA polymerase III (pol III) or
      heterodisperse RNA polymerase II (pol II) transcripts hybridizing to Alu could be
      detected in Alzheimer's disease (AD). RNA samples obtained from AD and control
      brain tissues were examined by Northern analysis for Alu and 7SL RNA expression.
      All RNA samples contained a prominent band of approximately 300 nucleotides which
      corresponds to 7SL RNA, the Alu-homologous RNA component of the signal
      recognition particle. In addition, three small (i.e. less than 300 nucleotide)
      7SL/Alu-hybridizing transcripts were detected. The two larger of the low
      molecular weight transcripts hybridized preferentially to the 7SL RNA probe,
      while the smallest transcript hybridized to the Alu probe. These transcripts and
      the heterodisperse RNA were variable in quantity and displayed a lack of
      correlation with AD.

PMID- 1378522
TI  - Specific inhibition of pituitary prolactin production by energy restriction in
      C3H/SHN female mice.
AB  - Pituitaries were excised from control (C; 95 kcal/week) or energy restricted (ER;
      48 kcal/week) female mice of 2, 3, 7, and 18 months of age. The total RNA and
      relative actin mRNA amounts in the pituitary were significantly greater in C than
      in ER mice both at 7 and 18 months. Prolactin (PRL) mRNA, standardized with actin
      mRNA, was significantly less in ER mice of 7 (50%) and 18 (51%) months of age
      than in age-matched controls, suggestive of specific inhibition of PRL mRNA
      transcription. Pituitary RNA and actin mRNA increased from 7 to 18 months in C
      mice but not in ER mice. Similarly, mean pituitary volumes increased between 2
      and 18 months in C mice but not in ER mice. PRL mRNA, standardized with actin
      mRNA, did not change in either C or ER mice 7-18 months of age. All examined C
      mice of 3, 7, and 18 months of age had estrous cycles but none of the ER mice of
      the same ages. After 1 month of ER, the pituitary volumes and serum insulin
      concentrations in 2-month-old female mice were reduced. Thus net reduction of PRL
      mRNA per pituitary by ER is attributable to decreases in pituitary size and
      specific inhibition of PRL production, both of which may be due to low estrogen
      and insulin levels.

PMID- 1378523
TI  - Mispairing and compensational changes during the evolution of mitochondrial
      ribosomal RNA.

PMID- 1378525
TI  - Antiviral agents: problems and promises.

PMID- 1378524
TI  - Phylogenetic relationships among the agent of bacillary angiomatosis, Bartonella
      bacilliformis, and other alpha-proteobacteria.
AB  - Bacillary angiomatosis (BA) and chronic bartonellosis are bacterial infections of
      humans which result in an unusual vascular proliferative tissue response. In
      order to determine their phylogenetic relationships, we have determined greater
      than 95% of the 16S rRNA sequences for these two organisms by amplification
      directly from infected BA tissue and from a Bartonella bacilliformis lyophilized
      culture. The BA agent and B. bacilliformis are closely related alpha
      proteobacteria (98.5%), although the BA agent is more closely related to
      Rochalimaea quintana (99.1%). Contrary to previous belief, the BA agent is
      distinct from, and less closely related to, the cat scratch bacillus (Afipia
      felis) (90.7%). We propose a novel secondary structure in a hypervariable region
      of the 16S rRNA which is useful for alignment of primary sequences and which may
      be useful for design of nucleic acid probes.

PMID- 1378527
TI  - [Changes in neutrophil functions and serum granulocyte colony-stimulating factor
      levels after gastrointestinal surgery: preliminary report].

PMID- 1378526
TI  - [The effect of FK506 on segmental pancreas allograft in mongrel dogs].
AB  - FK506 is a potent immunosuppressive agent on experimental and clinical organ
      transplantation. We studied the the effect of this agent on segmental pancreas
      allograft in mongrel dogs. Graft survival was prolonged significantly with
      continuous administration of FK506, 0.3mg/kg/day intramuscular and 1.0mg/kg/day
      orally. However such symptoms as loss of appetite, nausea and extreme emaciation
      were observed and caused death. While bolus therapy of FK506 (3 days
      administration with the dose of 1.0mg/kg i.m. from 4 to 6 day postoperatively)
      showed the same immunosuppressive effect as continuous therapy and less side
      effect. Furthermore it was suggested that FK506 plasma levels were concerned with
      the appearance of side effect. In conclusion, the administration of FK506 with
      plasma level monitoring was thought to be useful on pancreas transplantation.

PMID- 1378528
TI  - Identification of a transcriptional enhancer important for enteroendocrine and
      pancreatic islet cell-specific expression of the secretin gene.
AB  - It is well established that the gene encoding the hormone secretin is expressed
      in a specific enteroendocrine cell, the S cell. We now show that the secretin
      gene is transiently expressed in insulin-producing B cells of the developing
      pancreatic islets in addition to the intestine. Furthermore, secretin is produced
      by most established islet cell lines. In order to identify and characterize the
      regulatory elements within the secretin gene that control tissue-specific
      expression, we have introduced secretin reporter gene constructions into the
      secretin-producing HIT and STC-1 cell lines as well as the nonexpressing INR1-G9
      glucagonoma line. Analysis of deletion mutants revealed that sequences between
      174 and 53 bp upstream from the transcriptional start site are required for
      maximal expression in secretin-producing cells. This positive element functioned
      independently of position and orientation. Further deletions into the enhancer
      resulted in a stepwise loss of transcriptional activity, suggesting the presence
      of several discrete control elements. The sequence CAGCTG within the secretin
      enhancer closely resembles that of the core of the B-cell-specific enhancer in
      the insulin gene. Point mutations introduced into this putative element led to
      greater than 85% reduction in transcriptional activity. Gel mobility shift assays
      suggested that a factor in B cells closely related or identical to proteins that
      bind to the insulin enhancer interacts with the CAGCTG motif in the secretin
      gene.

PMID- 1378529
TI  - Evidence that glucocorticoid- and cyclic AMP-induced apoptotic pathways in
      lymphocytes share distal events.
AB  - WEHI7.2 murine lymphocytes undergo apoptotic death when exposed to
      glucocorticoids or elevated levels of intracellular cyclic AMP (cAMP), and these
      pathways are initiated by the glucocorticoid receptor (GR) and protein kinase A,
      respectively. We report the isolation and characterization of a novel WEHI7.2
      variant cell line, WR256, which was selected in a single step for growth in the
      presence of dexamethasone and arose at a frequency of approximately 10(-10). The
      defect was not GR-related, as WR256 expressed functional GR and underwent GR
      dependent events associated with apoptosis, such as hormone-dependent gene
      transcription and inhibition of cell proliferation. Moreover, the glucocorticoid
      resistant phenotype was stable in culture and did not revert after treatment with
      5-azacytidine or upon stable expression of GR cDNA. In addition, WR256 did not
      exhibit the diminished mitochondrial activity commonly associated with apoptosis.
      Interestingly, WR256 was also found to be resistant to 8-bromo-cAMP and forskolin
      despite having normal levels of protein kinase A activity and the ability to
      induce cAMP-dependent transcription. We examined the steady-state transcript
      levels of bcl-2, a gene whose protein product acts dominantly to inhibit
      thymocyte apoptosis, to determine whether elevated bcl-2 expression could account
      for the resistant phenotype. Our data showed that bcl-2 RNA levels were similar
      in the two cell lines and not altered by either dexamethasone or 8-bromo-cAMP
      treatment. These results suggest that WR256 exhibits a "deathless" phenotype and
      has a unique defect in a step of the apoptotic cascade that may be common to the
      glucocorticoid- and cAMP-mediated cell death pathways.

PMID- 1378530
TI  - Novel DNA-binding proteins regulate intestine-specific transcription of the
      sucrase-isomaltase gene.
AB  - Sucrase-isomaltase (SI) is an enterocyte-specific gene which exhibits a complex
      pattern of expression during intestinal development and in the adult intestinal
      mucosa. In the studies described in this report, we demonstrate that enterocyte
      specific transcription of the SI gene is regulated by an evolutionarily conserved
      promoter that extends approximately 180 bp upstream of the transcription start
      site. DNase I footprint analysis allowed the identification of three nuclear
      protein-binding sites within the SI promoter (SIF1, SIF2, and SIF3 [SI
      footprint]), each of which acted as a positive regulatory element for
      transcription in intestinal cell lines. SIF1 was shown to bind nuclear protein
      complexes present in primary mouse small intestinal cell and in an intestinal
      cell line (Caco-2). However, SIF1-binding proteins were absent in a variety of
      other epithelial and nonepithelial cells. In vitro mutagenesis experiments
      demonstrated that the SIF1 site is required for high-level promoter activity in
      intestinal cells. The SIF3 element formed prominent binding complexes with
      intestinal and liver nuclear extracts, whereas nuclear proteins from other
      epithelial and nonepithelial cells formed weaker complexes of different
      mobilities. The SIF2 element bound nuclear proteins in a pattern similar to that
      of SIF3, and cross-competition studies suggested that SIF2 and SIF3 may bind the
      same nuclear proteins. Taken together, these data have allowed the identification
      of novel DNA-binding proteins that play an important role in regulating intestine
      specific transcription of the SI gene.

PMID- 1378531
TI  - Spontaneous mutagenesis: experimental, genetic and other factors.
AB  - Spontaneous mutations are "the net result of all that can go wrong with DNA
      during the life cycle of an organism" (Glickman et al., 1986). Thus, the types
      and amounts of spontaneous mutations produced are the resultant of all the
      cellular processes that are mutagenic and those that are antimutagenic. It is not
      widely appreciated that the types and frequencies of spontaneous mutations change
      markedly with subtle changes in experimental conditions. All types of mutations
      are produced spontaneously, i.e., base substitutions, frameshifts, insertions and
      deletions. However, very few papers have appeared that are devoted exclusively to
      the study of the mechanisms of spontaneous mutagenesis, and of the subtle
      experimental factors that affect the types and frequencies of spontaneous
      mutations. This is unfortunate because spontaneous mutagenesis appears to play a
      major role in evolution, aging, and carcinogenesis. This review emphasizes subtle
      experimental variables that markedly affect the results of a spontaneous mutation
      experiment. A thorough understanding of these variables eliminates the need for a
      theory of "directed" mutagenesis. The intrinsic instability of DNA, and the types
      of normal metabolic lesions that are produced in DNA that lead to mutations via
      errors made in replication, repair, and recombination are reviewed, as is the
      genetic control of spontaneous mutagenesis. As with spontaneous mutagenesis,
      spontaneous carcinogenesis can also be considered to be the net result of all
      that can go wrong with DNA during the life of an organism.

PMID- 1378532
TI  - Cellular and molecular advances in elucidating p53 function.
AB  - The finding that in many human tumors there is allelic loss and/or mutations in
      p53, in combination with recognition that these events may play a role in multi
      stage carcinogenesis, has focused considerable interest on this gene. To help
      keep abreast of this rapidly expanding field, recent experiments on the role and
      potential regulation of p53 are described: these include discussions of p53 as an
      anti-proliferative agent, the p53 mutations found in human tumors and tumor cell
      lines, the conformational states of p53, phosphorylation of p53 by p34cdc2, and
      signals for the nuclear localization of p53. p53 may act as a transcriptional
      activator and the specific DNA sequences to which p53 protein binds are also
      discussed as is the importance of abrogation of p53 function in overcoming
      cellular senescence.

PMID- 1378533
TI  - The genotoxicity of industrial wastes and effluents.
AB  - A review of the literature published on the genotoxicity of industrial wastes and
      effluents using short-term genetic bioassays is presented in this document. The
      importance of this task arises from the ubiquity of genotoxic compounds in the
      environment and the need to identify the sources of contamination so that efforts
      aimed at control and minimization can be implemented. Of even greater
      significance is the immediate concern for the welfare of human health and the
      environment. Subheadings of this document include a description of the genetic
      bioassays that have been used to test industrial wastes, a compendium of methods
      commonly used to prepare crude waste samples for bioassay, and a review of the
      genetic toxicity of wastes and effluents. Wastes and effluents have been grouped
      according to industrial source. Major categories include chemical and allied
      products, pulp and paper manufacturing, defense and munitions, petroleum
      refining, primary metal industries, and miscellaneous industrial manufacturers.
      Within each industrial category, a synopsis of individual genetic toxicity
      studies is presented, followed by an interpretation of results on a
      comprehensive, industry-wide basis. In this evaluation, a discussion of the types
      and extent of genotoxic damage caused by a particular set of wastes is presented,
      and potential sources of genotoxic activity are identified. Concluding the
      document is a commentary, which discloses potential shortcomings in the way in
      which current legislation protects human heath and the environment from the
      release of genotoxic substances via industrial wastes and effluents. It also
      provides an assessment of the genotoxic burden that industrial wastes place on
      the environment.

PMID- 1378534
TI  - Mutagenic potency of heterocyclic amines towards Salmonella typhimurium; possible
      causes of variability in the results observed.
AB  - The potent food mutagens and carcinogens 2-amino-3-methylimidazol[4,5-f]quinoline
      (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MEIQ) and 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) are probably the most active bacterial
      mutagens so far discovered. Important discrepancies were found, however, in the
      specific mutagenicities published for these compounds. This paper analyzes a
      number of experimental factors that could explain these differences: purity of
      the compounds, stability under the experimental conditions employed, solvents
      used, bacterial toxicity, testing procedure, amount and age of the S9 fraction,
      dose-effect relationships, day-to-day variability, origin of the compounds
      investigated or of the bacterial strain and age of the strain culture used. None
      of these factors was found to play a critical role, when the other experimental
      conditions were strictly standardized. The in-house testing procedure used
      probably explains the interlaboratory variations observed.

PMID- 1378536
TI  - Mechanism of induction of micronuclei and chromosome aberrations in mouse bone
      marrow by multiple treatments of methotrexate.
AB  - Methotrexate (MTX), an inhibitor of dihydrofolate reductase (DHFR), slightly
      induced micronuclei and this induction of micronuclei was enhanced by multiple
      treatments with the drug (Yamamoto et al., 1981; Hayashi et al., 1984;
      CSGMT/JEM.MMS, 1990). More micronuclei and chromosomal aberrations in mouse bone
      marrow cells were induced by multiple than by single treatment. The MTX level in
      mouse plasma and bone marrow showed little (or no) differences between single and
      quadruple treatments several hours after the injection(s). On the other hand, the
      DHFR activity in bone marrow cells 3 h after one and four injections was
      decreased to approximately 38 and 0%, respectively, of that in non-treated mice.
      Furthermore, the intracellular MTX level in the bone marrow cells (but not in
      total bone marrow) after four injections was about 10-fold higher than that after
      one injection. The amount of MTX bound to protein 3 h after four injections, as
      assayed by gel filtration (Sephadex G-25), was approximately 8-fold greater than
      after one injection. Therefore, the multiple-dose effects of MTX on the induction
      of micronuclei and chromosomal aberrations may be explained by the intracellular
      accumulation of MTX resulting in an enhancement of enzyme inhibition.

PMID- 1378535
TI  - Genotoxic potential of crown ethers in mammalian cells: induction of sister
      chromatid exchanges.
AB  - Crown ethers are macrocyclic polyethers which possess ionophoric properties.
      These compounds are currently being studied for potential use as pharmaceutical
      agents as well as antibacterials. Though crown ethers have been shown to be
      highly toxic in prokaryotes and eukaryotes, there have been few investigations
      into the potential genotoxicity of these compounds. When sister-chromatid
      exchanges (SCEs) were quantitated after exposure to crown ethers, the results
      reflected no significant genotoxic effects on Chinese hamster V79 cells at any of
      the crown ether concentrations utilized. One crown ether, dicyclohexyl 21-crown
      7, did appear to possess antigenotoxic activity. The data on the induction of
      SCEs by crown ethers reported herein suggest that these compounds are not
      genotoxic in mammalian cells despite their cytotoxicity.

PMID- 1378539
TI  - Cytogenetic damage by melphalan and hyperthermia in patients with an initial
      epileptic attack.
AB  - Sister-chromatid exchanges (SCEs) and cell kinetics in cultured lymphocytes of
      patients with an initial epileptic attack, and prior to any anticonvulsant
      treatment, were studied. Spontaneous melphalan (MEL) and MEL-hyperthermia (MEL
      HYP) induced SCE frequencies have been studied in 18 adults with an initial
      epileptic seizure. Fifteen age and sex matched healthy subjects were used as the
      control group. The incidence of spontaneous SCEs in lymphocytes from epileptics
      was not significantly greater than in those from the control subjects. However,
      when exposed to MEL in vitro, cells from both groups showed an increase in SCE
      frequency. When exposed to MEL and HYP (41 degrees C for 3 h) in vitro, cells
      from both groups showed a further increase in SCE frequency with yields from
      epileptics higher (P less than 0.05) than from controls. HYP in combination with
      MEL enhanced synergistically SCEs and cell division delays in both groups with
      synergistic effects in cells from epileptics (P less than 0.01 and P less than
      0.01 respectively) higher than from controls (P less than 0.05 and P less than
      0.05 respectively.

PMID- 1378538
TI  - Detection of micronuclei after exposure to mitomycin C, cyclophosphamide and
      diethylnitrosamine by the in vivo micronucleus test in mouse splenocytes.
AB  - A micronucleus detection test using mouse splenocytes has been adapted from a
      method previously carried out using human lymphocytes. An ex vivo protocol was
      chosen: male C57B16 mice were treated with various compounds. Splenocytes were
      then isolated and placed in culture for 48 h and stimulated with concanavalin A
      and conditioned medium. The cytokinesis-block method reported by Fenech and
      Morley was used to detect and score micronuclei in the proliferating lymphocytes
      (3 micrograms/ml of cytochalasin B for 16 h). Three mutagenic clastogens,
      mitomycin C (MMC), a direct alkylating agent (0.4, 0.8 and 1.6 mg/kg),
      cyclophosphamide (CP), an indirect alkylating agent (25, 50 and 100 mg/kg) and
      diethylnitrosamine (DEN), an indirect alkylating agent with labile metabolites
      (25, 50 and 100 mg/kg), were tested at four sampling times (2, 4, 8 and 15 days).
      All three compounds were detected from 48 h after treatment. This method was
      indeed able to detect clastogenic compounds normally detected by the mouse bone
      marrow micronucleus test (MMC, CP) as well as a compound with labile metabolites
      which is not usually detected by this test (DEN). Maximum micronucleus induction
      was observed after 4 days for MMC, 2 days for CP and 15 days for DEN. This method
      thus appears to offer a potentially useful toxicological test for assessing in
      vivo clastogenicity.

PMID- 1378537
TI  - DNA damage induced by carcinogenic lead chromate particles in cultured mammalian
      cells.
AB  - Particulate lead chromate is a highly water-insoluble cytotoxic and carcinogenic
      agent, but its mechanism of action remains obscure. We investigated its effects
      on DNA damage in CHO cells after a 24-h exposure using alkaline or neutral filter
      elution and cytogenetic studies. Concentrations (0.08, 0.4 and 0.8
      micrograms/cm2), which reduced the colony-forming efficiency of CHO cells to 94,
      50 and 10%, respectively, produced dose-dependent DNA single-strand breaks and
      DNA-protein crosslinks, but no DNA double-strand breaks or DNA-DNA crosslinks
      were observed. The single-strand breaks were absent from cells given a 24-h
      recovery period after removal of the treatment medium, even though most of the
      particles remained adhered to cells and to the culture dish. In contrast, both
      the DNA-protein crosslinks and chromosomal aberrations persisted even after the
      24-h recovery period. These results suggest that the mechanism of the particle
      induced early DNA single-strand breaks may be different from DNA-protein
      crosslinks and the lesions leading to chromosomal aberrations, or alternatively,
      that the repair of single-strand breaks is more efficient than the repair of DNA
      protein crosslinks in the unavoidable continuing presence of carcinogen. These
      results also suggest that the chromosome damage may be related to the persistent
      DNA-protein crosslinks, and further confirm the genotoxic activity of
      carcinogenic lead chromate particles.

PMID- 1378540
TI  - Evaluation in Drosophila melanogaster of the mutagenic potential of furfural in
      the mei-9a test for chromosome loss in germ-line cells and the wing spot test for
      mutational activity in somatic cells.
AB  - The mutagenic potential of furfural was evaluated by means of the chromosome loss
      test in germ cells and the wing spot test in somatic cells of Drosophila
      melanogaster. The chromosome loss test was carried out employing repair
      proficient as well as repair-deficient females. Males carried the compound Y
      chromosome, BSYy+. Two routes of administration were used: injection and feeding
      of adult males. Genetic damage was demonstrable after matings of treated males
      with females carrying the excision repair-deficient mutant mei-9a. The somatic
      mutation and recombination test was carried out treating 72-h transheterozygous
      mwh+/+flr3 larvae. Acute treatment of larvae was chosen as the method of
      exposure. Evidence indicates that furfural induces somatic damage as measured in
      the wing spot test.

PMID- 1378541
TI  - Mutagenicity of nitro-azabenzo[a]pyrene and its related compounds.
AB  - The mutagenicity of nitrated benzo[a]pyrene (BP) and the related compounds, 1-
      and 3-nitrobenzo[a]pyrene (NBP), 1- and 3-nitro-6-cyanobenzo[a]pyrene (N-6-CBP),
      1- and 3-nitro-6-azabenzo[a]-pyrene (N-6-ABP), 1- and 3-nitro-6-azabenzo[a]
      pyrene-N-oxide (N-6-ABPO) and 1,6- and 3,6-dinitrobenzo[a]-pyrene (DNBP), was
      investigated. The mutagenic activities of 3-N-6-CBP and 3-N-6-ABP were 117 and 76
      times, respectively, that of 3-NBP. In addition, 3,6-DNBP was more mutagenic than
      1,6-DNBP. It is suggested that the mutagenic activation differs with the position
      of NO2 substitution in the chemical structure. A nitro derivative with NO2
      substitution at the 3 position of the aromatic ring of BP was more mutagenic than
      that with the substitution at the 1 or 6 position. The reducibility of DNBPs was
      then determined by detecting 1- or 3-amino-6-nitrobenzo[a]pyrene (A-6-NBP), a
      metabolite of DNBP; 3,6- and 1,6-DNBP were reduced to 3- and 1-A-6-NBP at
      frequencies of 958 +/- 26 and 79 +/- 8, respectively, pmole per mg of protein,
      when the compound was incubated anaerobically with rat liver S9 mix at 37 degrees
      C for 15 min. NO2 substituted at the 3 position of the aromatic ring of BP was
      readily reduced by a microsome enzyme to form an amino derivative. The result
      suggests that these compounds have a structure-activity relationship between
      mutagenicity and NO2 substitution of BP.

PMID- 1378542
TI  - Vinblastine treatment induces dose-dependent increases in the frequency of
      micronuclei in mouse bone marrow.
AB  - The effect of various doses (0.005-2.0 mg/kg b.w.) of vinblastine sulfate (VBL)
      was studied on the induction of micronuclei in polychromatic and normochromatic
      erythrocytes (PCE, NCE) of the bone marrow of female BALB/c mice. VBL treatment
      resulted in a dose-dependent increase in the frequency of micronucleated PCE and
      NCE, while the PCE/NCE ratio and mitotic index declined with increasing drug
      dose. The dose-effect curves were linear quadratic for all the parameters
      studied.

PMID- 1378544
TI  - Induction of sister-chromatid exchanges by 2-aminofluorene in cultured human
      lymphocytes with and without erythrocytes.
AB  - 2-Aminofluorene (2-AF), an indirect mutagen reported to be metabolically
      activated by erythrocytes in the Salmonella mutagenicity test, was studied for
      the induction of sister-chromatid exchanges (SCEs) in human lymphocytes in vitro
      with (whole-blood cultures) and without erythrocytes (isolated lymphocyte
      cultures). 2-AF (0.025-0.8 mM) was present in the cultures for the last 48 h of
      72-h cultures. In both types of culture, SCEs increased in a dose-dependent
      manner, with a statistically significant elevation already at the lowest
      concentration of 2-AF tested and maximum responses of 2.4-fold (whole blood) and
      2.1-fold (isolated lymphocytes), in comparison with mean SCEs/cell in control
      cultures, at 0.4 and 0.2 mM concentrations (respectively). Thus, the induction of
      SCEs by 2-AF was not dependent on the presence of erythrocytes. Styrene (2 mM), a
      positive control chemical known to require erythrocytes for efficient SCE
      induction in vitro, was shown to produce a 4.9-fold increase in SCEs in whole
      blood cultures, but only a slight (1.3-fold) effect in isolated lymphocyte
      cultures. The results suggest that leukocytes, but not erythrocytes, are
      important in the metabolic activation of 2-AF in the human lymphocyte SCE assay.

PMID- 1378543
TI  - Mutagenic effects of niridazole in animal-mediated and in liquid suspension
      assays using Escherichia coli K-12 as an indicator.
AB  - The mutagenic effects of the antischistosomal drug niridazole (1-(5-nitro-2
      thiazolyl)-2-imidazolidinone) were investigated in liquid suspension and
      intrasanguineous animal-mediated assays with mice. As indicator strains
      Escherichia coli K-12 343/113 (Nir(S)) and a newly constructed niridazole
      nitroreductase-deficient derivative (Escherichia coli K-12 343/113 Nir(r) 200)
      were used. With the parental strain (Nir(S)) induction of nalidixic acid- and
      valine-resistant mutants was observed under in vivo conditions in the liver and,
      to a lesser extent, in the spleen. Positive results were also found when
      intestinal homogenates, blood sera, and urine samples of niridazole-treated
      animals were tested in vitro with the wild-type strain. With Escherichia coli K
      12 343/113 Nir(r) 200 no clear-cut positive results were obtained in animal
      mediated assays. In liquid suspension assays positive results were restricted to
      the urine samples. These findings indicate that the positive results obtained
      with the wild-type strain are due to nitroreduction and that the concentrations
      of mutagenic metabolites formed by activation processes in the living animal are
      too low to enable their detection in inner organs, intestines, and the blood with
      the reductase-deficient strain. In agreement with our present findings showing
      increased genotoxicity in urine, niridazole causes tumors in rodents
      preferentially in the kidneys and in the bladder.

PMID- 1378545
TI  - 32P-postlabelling analysis of DNA from human tissues.
AB  - DNA extracted from human lung, bladder, liver, pancreas, cervix and breast tissue
      samples taken at autopsy (37 sample sets) was analysed by the nuclease P1
      enhancement modification of the 32P-postlabelling assay for levels of aromatic
      carcinogen DNA adducts. Results were combined with those from a previous study
      for statistical analysis of 56 sample sets (32 male+24 female). A strong trend
      was seen for increased adduct levels in the lung DNA of smokers and a weak
      association for the bladder DNA of smokers compared to non-smokers. Aromatic
      adducts were also detected in other tissues.

PMID- 1378546
TI  - Suppressing effects of glucan on micronuclei induced by cyclophosphamide in mice.
AB  - The effect of pretreatment with carboxymethylglucan (CMG) on the frequency of
      micronuclei induced by cyclophosphamide administration in mice was evaluated. Two
      doses of CMG (50 mg/kg body weight) injected either intraperitoneally 24 h or
      intravenously 1 h prior to two cyclophosphamide administrations (80 mg/kg)
      significantly decreased the frequency of micronucleated PCE in bone marrow. Of
      two evaluated derivatives of carboxymethylglucan, the K3 derivative was most
      efficient. The results show that it is possible to achieve a suppressive effect
      of soluble carboxymethylglucan prepared from Saccharomyces cerevisiae against
      cyclophosphamide mutagenicity. The notion may be useful for glucan's effects
      against pharmacocarcinogenesis. Therapeutic application of glucan with
      cyclophosphamide therapy may provide a remarkable decrease of the secondary
      tumour risk. The utilization of these results for human patients needs to be
      considered.

PMID- 1378547
TI  - Melphalan, a second chemical for which specific-locus mutation induction in the
      mouse is maximum in early spermatids.
AB  - Melphalan (MLP), a bifunctional alkylating agent structurally related to the
      highly mutagenic chemical chlorambucil (CHL), was found to induce high
      frequencies of specific-locus mutations in postspermatogonial germ cells of the
      mouse, and to be one of only a few chemicals that is also mutagenic in
      spermatogonial stem cells. Productivity patterns following MLP exposures
      resembled those that had been found for CHL. Mutation rates in successive male
      germ-cell stages were measured at three MLP-exposure levels in a total of 95,375
      offspring. While the induced (experimental minus historical-control) mutation
      rate is relatively low in stem-cell spermatogonia (1.2 x 10(-5) per locus at a
      weighted-mean exposure of 7.3 mg/kg), it is about 5 times higher in poststem-cell
      stages overall, and peaks at 26.7 x 10(-5) per locus in early spermatids at a
      weighted-mean exposure of only 5.7 mg/kg. This "type-2 pattern" of mutation yield
      (Russell et al., 1990), i.e., peak sensitivity in early spermatids, has
      heretofore been found for only one other chemical, CHL. Mutation-rate data
      earlier reported for CHL (Russell et al., 1989) were augmented in the present
      study for comparison with MLP-induced rates. Because of the greater toxicity of
      MLP, average exposures used for this chemical were only about one-half of those
      for CHL. When MLP and CHL mutation rates are extrapolated to equimolar doses,
      they appear very similar for poststem-cell stages overall. However, in the case
      of CHL, a somewhat higher proportion of the mutations is induced in early
      spermatids than in the case of MLP.

PMID- 1378548
TI  - Simultaneous evaluation of clastogenicity, aneugenicity and toxicity in the mouse
      micronucleus assay using immunofluorescence.
AB  - An improved antikinetochore antibody technique was established in the mouse
      micronucleus assay to simultaneously evaluate toxicity, clastogenicity and
      aneugenicity induced by various test agents. The procedure involved the use of
      cellulose column fractionated cytospun slides for analysis. The staining method
      consisted of sequential treatment of slides with crest serum, fluorosceinated
      goat-antihuman and swine-antigoat antibodies, and propidium iodide. In this
      method, polychromatic erythrocytes (PCEs, dark red), normochromatic erythrocytes
      (NCEs, green), chromosome(s)/fragments/micronuclei (orange), and kinetochores
      (yellow), are identified using the same filter setting under blue excitation (440
      490 nm) with a barrier filter at 520 nm. Using this method, three agents,
      cyclophosphamide, X-rays and vincristine were tested for micronucleus/aneuploidy
      induction and bone marrow toxicity. The aneugen, vincristine, and clastogens, X
      rays and cyclophosphamide, induced predominantly kinetochore positive (K+) and
      negative (K-) micronucleated PCEs, respectively. At the doses tested,
      cyclophosphamide caused a slight but statistically significant decrease in PCEs
      in females, and other agents did not produce any severe bone-marrow toxicity in
      either male or female mice. These results are comparable with the results
      reported in the literature on these compounds with various methods and thus
      demonstrate the usefulness of this assay in distinguishing clastogenicity from
      aneugenicity and in evaluating toxicity.

PMID- 1378549
TI  - The clastogenic potential in vitro of pyrrolizidine alkaloids employing
      hepatocyte metabolism.
AB  - Three pyrrolizidine alkaloids (PAs), monocrotaline, retrorsine and isatidine,
      were tested for their clastogenic activity under different conditions of
      metabolic activation in vitro. All three compounds exhibited a weak activity when
      V79 cells were treated at very high concentrations for 18 h in the absence of a
      metabolizing system. Short-term (2 h) treatment with rat liver S9 mix led to a
      strong and concentration-dependent increase in chromosomal aberrations for
      retrorsine. Isatidine was not mutagenic with S9 mix and monocrotaline was
      positive at high concentrations only. In contrast, a prolonged treatment (18 h)
      in vitro under activation conditions in the presence of primary hepatocytes led
      to clear concentration-dependent positive responses for all three PAs
      investigated. Particularly the results with isatidine demonstrate that in vitro
      tests using S9 mix for metabolization can generate misleading results. It is not
      clear whether the results could be attributed to a better activation of the test
      compounds by intact hepatocytes in comparison to S9 mix or if the fact that only
      hepatocytes allow a treatment for the whole culture period under activation
      conditions was more important. Owing to its strong cytotoxicity the exposure to
      S9 mix is generally limited to 2-4 h, limiting also the exposure of the target
      cells to a test chemical as well as its metabolites. The results presented show
      significant differences in mutagenic potency of PAs due to variations in the
      activation system. This underlines the usefulness of primary hepatocytes, e.g.,
      for the detection of pre-mutagens. The PAs investigated are present in plants
      which are used for phytotherapeutic medicinal products. They do not contribute to
      their efficacy and are, therefore, not to be tolerated in amounts that may impose
      a risk for the user.

PMID- 1378550
TI  - Modified metabolism of a carcinogen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp
      P-2), by liver S9 from Schistosoma japonicum-infected mice.
AB  - Schistosoma japonicum infection has been associated with an increased incidence
      of liver and colorectal cancers in humans. To explore the mechanisms underlying
      this association, we investigated the carcinogen-metabolizing properties of liver
      S9 preparations from S. japonicum-infected mice and compared them with those of
      S9 from uninfected animals. When the carcinogen 3-amino-1-methyl-5H-pyrido[4,3
      b]indole (Trp-P-2) was incubated with these S9s and the products were analyzed by
      high-performance liquid chromatography, we observed that the S9 from infected
      mice had a lower ability to convert Trp-P-2 into 3-hydroxyamino-1-methyl-5H
      pyrido[4,3-b]indole (Trp-P-2(NHOH)), an activated form of promutagenic Trp-P-2,
      than the S9 from uninfected mice. We found that both of these S9 preparations
      have a high ability to reduce Trp-P-2(NHOH) into Trp-P-2; however, the infected
      mouse S9 showed a significantly greater reducing power than the control S9. This
      difference appears to be responsible for the observed lower mutagen-activating
      potential of the infected mouse S9. These results suggest that hepatic enzyme
      activities of S. japonicum-infected mice are quantitatively different from those
      of normal mice.

PMID- 1378551
TI  - Mutagenic specificity in DNA base sequence by irradiation of health lamp light
      (UV-B) in Escherichia coli.
AB  - A shuttle vector, pZ189, carrying a bacterial suppressor tRNA marker gene, was
      irradiated with health lamp (HL) light containing UV-B. Plasmid mutations were
      scored by transforming an indicator strain of Escherichia coli carrying a
      suppressive blue amber mutation in the beta-galactosidase gene. Plasmid survival
      was also measured by transforming activity of the indicator strain. The majority
      of mutations induced by HL light were GC-AT transitions (69%) and the rest were
      transversions (31%). Some hot-spots in the mutations were observed by sequencing
      the suppressor gene. Mutagenic specificity in DNA base sequences induced by HL in
      E. coli agrees well with previous reports about 254-nm or 313-nm light effects on
      mammalian cells. This agreement may depend on the substitution of the inserted
      base instead of a G residue at the opposite site of a damaged C residue from
      conformational change of DNA structure in both bacterial and mammalian cells.

PMID- 1378553
TI  - Characterization of the progeny of X-ray irradiated males from two Drosophila
      virilis strains differing in genetic instability.
AB  - Significant effects of X-ray treatment on the increase in the number of
      phenotypic variations, two visible mutations, and chromosome aberrations were
      found in the progeny of irradiated males from the D. virilis laboratory stock
      that is capable of hybrid dysgenesis syndrome induction. This effect is much more
      pronounced than in the progeny of irradiated males from strong wild-type strains
      studied. A correlation between genetic instability and chromosome
      radiosensitivity was outlined. The mechanism of this phenomenon and the
      possibilities of using the property of genome instability for the productive
      induction of gene and chromosome damage in radiation mutagenesis experiments are
      discussed.

PMID- 1378552
TI  - Sampling times in micronucleus testing.
AB  - A series of micronucleus inducers were evaluated in the mouse bone marrow
      micronucleus test to determine if a 72-h sampling time enhances the sensitivity
      for detecting genotoxic agents. Male and female Swiss albino mice were dosed once
      with 7,12- dimethylbenz[a]anthracene, 6-mercaptopurine, benzo[a]pyrene, benzene,
      cyclophosphamide, 2-acetylaminofluorene, tubulazole, or mitomycin C. According to
      the EEC and OECD guidelines, the mice were killed at 24, 48 and 72 h after
      dosing. All test compounds induced an increase in the number of micronucleated
      polychromatic erythrocytes at 24 and/or 48 h. From the results obtained, it was
      evident that the 72-h sampling time does not enhance the sensitivity of the
      micronucleus test. The present data show that for screening purposes two sampling
      times at 24 and 48 h are sufficient to detect clastogens as well as aneugens.
      Although quantitative differences were found in sensitivity to micronucleus
      inducers between male and female mice, no qualitative differences were observed
      between the two sexes.

PMID- 1378554
TI  - Inhibition of recA induction by the radioprotector 2-mercaptoethylamine.
AB  - Our earlier finding that the radioprotective action of 2-mercaptoethylamine (MEA)
      is counteracted by ascorbate suggests a biochemical mechanism of action, which is
      supported by observations that MEA is not radioprotective in Rec- E. coli
      strains. In this study we show that MEA inhibits the induction of the recA gene
      by UV- or gamma-irradiation or by nalidixic acid in Escherichia coli strain GE94,
      which contains a recA-lacZ fusion. This effect, which may be counteracted by
      cysteine, indicates that in general MEA inhibits the induction of SOS functions.

PMID- 1378555
TI  - No increase in chromosome aberrations in workers from an oil catalytic cracking
      plant.
AB  - A study of structural chromosome aberration frequencies in blood lymphocytes was
      performed in a group of 20 oil catalytic cracking unit workers and in 26 subjects
      belonging to the office staff of an oil refining plant, as well as in 35 matched
      controls. Subjects in the latter group were of the same sex (males) and similar
      age as the exposed group, and had similar smoking habits. Benzo[a]pyrene levels
      in workplace air samples were also determined. The cytogenetic analysis failed to
      show any differences between the exposed and control groups. A slight increase in
      benzo[a]pyrene level above the Cuban national standard of 1 ng/m3 was found
      during the air sample analysis in the oil catalytic cracking unit.

PMID- 1378556
TI  - Sister-chromatid exchanges in beta-thalassaemic patients under conditions of in
      vivo and in vitro depletion of folic acid.
AB  - In order to investigate the effect of folate depletion, lymphocyte sister
      chromatid exchange (SCE) rates were compared among homozygous beta-thalassaemic
      patients with low folic acid levels, heterozygous beta-thalassaemic patients with
      normal folate levels and healthy persons with normal haemoglobin, in cultures
      with both normal and depleted folate conditions. Significantly higher SCE rates
      were found in homozygous patients in all assays, but the in vitro folate
      depletion did not induce an increase in SCE frequency in any group.

PMID- 1378558
TI  - A simple and convenient method for gaining pure populations of lymphocytes at the
      first mitotic division in vitro.
AB  - This paper describes a simple method for obtaining pure populations of human
      lymphocytes at the first in vitro mitotic division (M-1) by continuous treatment
      with colchicine or colcemid. When colchicine (7.2 x 10(-8) M) or colcemid (4.8 x
      10(-8) M) was added to cultures 0-24 h after initiation, cultures harvested at 54
      h had more than 99.9% of mitotic cells in the first metaphase (M-1). We showed
      that not only more analyzable M-1 cells may be obtained, but staining for sister
      chromatid differentiation may be avoided.

PMID- 1378557
TI  - The presence of genotoxic and bioactive components in indigo dyed fabrics--a
      possible health risk?
AB  - Extracts of pure cotton and jeans fabrics were tested for mutagenicity in
      Salmonella typhimurium strains TA98 and TA100. The vat dye indigo, technical
      grade as well as 98% and greater than 99.5% pure, was also tested for
      mutagenicity. Synthetic indigo, indirubin and isatin were tested for TCDD
      receptor affinity in competition experiments in vitro. The mutagenicity of the
      extracts was associated with the cotton denim and nondyed cotton gave only
      marginal effects. The mutagenicity of the indigo dyed fabrics was dependent on
      type and treatment of the fabrics. Extracts of both bleached and nonbleached
      jeans gave mutagenic effects on TA98 +/- S9 and TA100 +/- S9. The greatest
      effects were seen in the presence of S9. Bleaching gave an additional increase in
      the mutagenicity in the absence of S9. Normal washing of the fabrics after
      bleaching reduced the mutagenicity. Synthetic indigo of technical grade or 98%
      pure showed mutagenic effects, especially on TA98 + S9. Further purification to
      99.5% reduced the mutagenicity to 24 revertants/mg (6.2 rev/mu mole). Considering
      the amount of indigo in the extracts and its low mutagenicity, the genotoxicity
      of jeans extracts must be caused by other unknown components. However, indigo
      showed a high (Kd = 1.9 nM) affinity for the Ah or TCDD receptor. Indigo can
      therefore still be a potential health risk either by eliciting toxic effects of
      other compounds or by being a nongenotoxic carcinogen. The worldwide use of jeans
      with a possible exposure of a large population to genotoxic and biologically
      active components emphasizes the need for a more thorough characterization of
      these effects.

PMID- 1378559
TI  - Relationship between plasma levels of hyaluronic acid and amyloid-associated
      osteoarthropathy in chronic hemodialysis patients.
AB  - Plasma levels of hyaluronic acid (HA) and acute-phase reactants were determined
      in chronic hemodialysis patients with or without carpal tunnel syndrome (CTS)
      and/or shoulder pain, which are characteristic symptoms of amyloid-associated
      osteoarthropathy. While levels of acute-phase reactants tended to be higher in
      the patients with CTS and/or shoulder pain than in patients without these
      symptoms, the difference was not significant. However, plasma levels of HA were
      significantly higher in the patients with these symptoms. Analysis of plasma
      levels of HA in age-matched patients also demonstrated a significant correlation
      between elevated levels of HA and the presence of CTS and/or shoulder pain. Among
      the patients with CTS and/or shoulder pain, those patients with bone cysts in the
      carpal bone or humeral head had significantly higher plasma levels of HA than
      patients without bone cysts. Thus, there appears to be a relationship between
      elevated plasma HA and amyloid-associated osteoarthropathy in chronic
      hemodialysis patients that is more specific than any correlation with levels of
      acute-phase reactants.

PMID- 1378560
TI  - Glomerular deposition of alpha 2-macroglobulin in a child with steroid refractory
      nephrotic syndrome.
AB  - A four-year-old male with steroid refractory nephrotic syndrome was found to have
      diffuse deposition of alpha 2-macroglobulin (alpha 2M) in the glomeruli which
      showed diffuse mesangial proliferation and partial hyalinization by light
      microscopy. Camostat mesylate, a commercially available synthetic proteinase
      inhibitor, led to biochemical and clinical improvement. Twenty-two patients with
      7 biopsy-proven renal diseases did not have any deposition of alpha 2M in their
      kidney tissue. Though the pathogenetic mechanism is unknown, this is probably the
      first report of the deposition of alpha 2M in renal tissue.

PMID- 1378561
TI  - Analysis of tumor necrosis factor and lymphotoxin secreted by incubation of
      lymphokine-activated killer cells with tumor cells.
AB  - This study investigated the secretion of a tumor necrosis factor (TNF) and
      lymphotoxin (LT) from lymphokine-activated killer (LAK) cells during co-culture
      with glioblastoma cell lines, autologous glioma cells, and other non-gliomatous
      tumor cell lines (K562 and Daudi). Cytokine secretion from peripheral blood
      mononuclear cells (PBMC) was also examined. The TNF activity of culture
      supernatants was measured by L cell cytotoxic assay, and a neutralization test
      using anti-TNF and/or anti-LT antibodies determined whether the cytotoxic
      activity was due to TNF or LT. The results show that LAK cells secrete both TNF
      and LT during monoculture and release increased amounts of TNF and LT with non
      gliomatous tumor cell stimulation, but PBMC secrete only TNF with tumor cell
      stimulation. Glioblastoma or anaplastic astrocytoma cells, however, did not
      stimulate cytokine secretion from either LAK cells or PBMC. This indicates a
      discrepancy between the capability of LAK cells to lyse malignant glioma cells
      and cytokine secretion from LAK cells, and suggests that malignant glioma cells
      may produce some factors which inhibit cytokine secretion from LAK cells.

PMID- 1378562
TI  - Cortical and subcortical cavernous angioma: a comparison of patients with and
      without hemorrhage as the initial symptom.
AB  - Cavernous angioma is a benign vascular hamartoma with an obscure etiology.
      Clinical, radiological, and histological features of 24 cases of cortical and
      subcortical cavernous angiomas were analyzed to investigate the etiology. The
      lesions were classified as hemorrhaging (8 cases) or non-hemorrhaging (16 cases)
      according to the initial symptom. Age, sex, location, calcification and
      postcontrast enhancement by computed tomography (CT), tumor staining by
      angiography, and calcification and hemosiderin by histological examination were
      analyzed. Multivariate analysis showed that calcification by CT and histological
      examination correlated with non-hemorrhaging cases. Histological examination
      showed that calcification occurred inside and outside the blood vessels, within
      the vessel walls and in the adjacent brain tissue. Hemosiderin was also seen in
      most cases. These findings suggest that cavernous angiomas without hemorrhage
      have a poor circulation, resulting in minor recurrent bleeding and thrombosis, as
      well as calcification.

PMID- 1378563
TI  - Choroid plexus arteriovenous malformations.
AB  - Among 24 arteriovenous malformations (AVMs) involving the choroid plexus, 11 were
      plexal type AVMs predominantly located in the choroid plexus of the lateral
      ventricle, and 13 were parenchymal type AVMs mainly situated in the
      paraventricular cerebral parenchyma. 83% of all AVMs involved both the choroid
      plexus and the paraventricular cerebral parenchyma. Most cases presented with
      intracranial hemorrhage, particularly intraventricular hemorrhage. The most
      serious surgical problem was a small residual nidus unrecognized at the initial
      operation causing postoperative hemorrhage. Five parenchymal type AVMs presented
      residual niduses in the choroid plexus, causing death in two cases. Two plexal
      type AVMs resulted in residual AVMs supplied by the cisternal segment of the
      anterior choroidal artery, situated in the medial temporal lobe. To prevent
      postoperative hemorrhage from a small residual nidus, immediate postoperative
      angiography while the patient is still under general anesthesia should be
      performed to identify any residual nidus.

PMID- 1378564
TI  - Chronic subdural hematoma in elderly people: present status on Awaji Island and
      epidemiological prospect.
AB  - The epidemiological aspect of chronic subdural hematoma (CSH) in the elderly who
      are 65 years old or elder was evaluated on Awaji Island with about 170,000
      inhabitants. The overall incidence of CSH was 13.1 per 100,000/year, 3.4 in
      people under 65 years old, and 58.1 in the elderly. The elderly were 17.7% of all
      inhabitants. If these incidences of CSH are extrapolated to all of Japan in the
      year 2020, the incidence will be 16.3 per 100,000/year. This suggests that CSH
      may become the most common neurosurgical condition.

PMID- 1378565
TI  - Entrapment of the temporal horn: a form of focal non-communicating hydrocephalus
      caused by intraventricular block of cerebrospinal fluid flow--report of two
      cases.
AB  - In two cases of entrapment of the temporal horn, computed tomography demonstrated
      the typical appearance of a comma-shaped homogeneous area isodense with water
      surrounded by a periventricular low-density area. The cause was probably choroid
      plexitis resulting in obstruction of the cerebrospinal fluid pathway at the
      atrium. External drainage followed by shunt emplacement is indicated.

PMID- 1378567
TI  - Association of meningioma and ependymoma--case report.
AB  - We report the rare association of a meningioma and an ependymoma in a young boy.
      A meningioma was detected in the left cerebellopontine angle at age 8 months, and
      an ependymoma in the left frontal lobe 2 years later. Chromosomal analysis was
      normal, and his family showed no signs of phacomatosis. Both tumors were totally
      removed, and he recovered well after both operations.

PMID- 1378566
TI  - Effect of long-term treatment with somatostatin analogue (SMS 201-995) on
      pituitary tumor shrinkage in acromegaly--report of two cases.
AB  - The effect of long-term somatostatin analogue (SMS 201-995) treatment in two
      acromegalic patients is reported. Continuous tumor shrinkage was observed even
      after 129 and 139 weeks of treatment with 600 micrograms of SMS 201-995 daily. A
      huge and firm adenoma underwent shrinkage during treatment with SMS 201-995. No
      serious side effect appeared during 160 weeks of treatment. SMS 201-995 has a
      longterm tumor shrinkage effect and improves endocrinopathies.

PMID- 1378568
TI  - Successful removal of intracavernous neurinoma originating from the oculomotor
      nerve--case report.
AB  - An oculomotor neurinoma was confirmed intraoperatively to be located in the
      lateral wall of the cavernous sinus in a 55-year-old male. By protruding into the
      true venous cavity, it caused obliteration of the blood flow in the cavernous
      sinus. The tumor was totally removed without entering the true venous cavity of
      the cavernous sinus. The cavernous sinus was closed by suturing the dural
      membrane to the thin fibrous membrane, preventing intraoperative bleeding.

PMID- 1378569
TI  - Aneurysm arising at the triplicate anterior communicating artery--case report.
AB  - A very rare case of triplicate anterior communicating artery associated with
      ruptured aneurysm in a 21-year-old female is reported. The triplicate
      configuration was not predicted by preoperative cerebral angiography, but found
      intraoperatively. The aneurysm was trapped successfully, and she recovered with
      no neurological deficit.

PMID- 1378570
TI  - Cerebral sinus thrombosis in patient with ulcerative colitis--case report.
AB  - Left transverse sinus thrombosis developed in a 27-year-old male with ulcerative
      colitis. The diagnosis was based on cerebral angiography and magnetic resonance
      (MR) imaging, the latter of which clearly delineated the intraluminal thrombus.
      Serial MR images demonstrated thrombus organization. The use of this method in
      the diagnosis of cerebral sinus thrombosis might reduce the need for cerebral
      angiography.

PMID- 1378571
TI  - Aging impairs estrogenic suppression of hypothalamic proopiomelanocortin
      messenger ribonucleic acid in the mouse.
AB  - Altered neuroendocrine sensitivity to estrogen is a characteristic of
      reproductive aging in female rodents, but its molecular basis is not well
      understood. The objective of this study was to determine whether altered
      modulation of hypothalamic proopiomelanocortin (POMC) mRNA by estradiol (E2) is a
      component of reduced neuroendocrine sensitivity to estrogen in the aging mouse.
      Young (4 month-old), middle-aged (13 month-old), and old (25 month-old) C57BL/6J
      mice were ovariectomized, implanted 2 weeks later with Silastic capsules
      containing E2 or cholesterol (CHOL), and sacrificed 3 days later. Hypothalamic
      POMC mRNA was measured by solution hybridization/RNase protection, using a RNA
      probe complementary to a fragment of mouse POMC mRNA. In the group with CHOL
      implants, POMC mRNA was 36% lower in middle-aged and old mice compared to young
      mice. E2 treatment reduced POMC mRNA levels by 44% in young mice but failed to
      lower POMC mRNA in middle-aged and old animals. These results confirm earlier
      evidence of reduced levels of POMC mRNA in hypothalami of aging rodents and
      indicate that the ability of E2 to reduce hypothalamic POMC mRNA is lost by
      middle age.

PMID- 1378572
TI  - Neurochemical changes in the rat brain after intraventricular administration of
      tryptamine-4,5-dione.
AB  - Tryptamine-4,5-dione (4,5-DKT) a neurotoxic derivative of serotonin (5-HT), was
      injected into the lateral ventricle of the rat in order to evaluate its
      biochemical effects. The levels of 8 substances in the hippocampus, striatum and
      prefrontal cortex were examined 3, 7 and 14 days after treatment with 4,5-DKT. 5
      Hydroxytryptamine and 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased
      in all three regions by days 7 and 14, respectively. Tryptamine-4,5-dione had no
      significant effect on dopaminergic or adrenergic systems or on the levels of L
      tryptophan and L-tyrosine, in any of the three areas of brain examined. Reduced
      activity of tryptophan hydroxylase in the cortex was observed 14 days after
      administration of 4,5-DKT. However, administration of 4,5-DKT did not alter the
      binding of [3H]paroxetine, a specific antagonist of the uptake of 5-HT, to nerve
      terminals. These results indicate that 4,5-DKT produced depletion of 5-HT without
      eliminating serotoninergic nerve terminals.

PMID- 1378573
TI  - Aggregation of the amyloid precursor protein within degenerating neurons and
      dystrophic neurites in Alzheimer's disease.
AB  - Using a monoclonal antibody raised against purified, native, human protease nexin
      2/amyloid precursor protein, which recognizes an amino terminal epitope on the
      amyloid precursor protein and detects all major isoforms of amyloid precursor
      protein, we examined the localization of the amyloid precursor protein within
      Alzheimer's and aged control brains. Very light cytoplasmic neuronal amyloid
      precursor protein staining but no neuritic staining was visible in control
      brains. In the Alzheimer's brain, we detected numerous amyloid precursor protein
      immunopositive neurons with moderate to strong staining in select regions. Many
      neurons also contained varying levels of discrete granular, intracellular
      accumulations of amyloid precursor protein, and a few pyramidal neurons in
      particular appeared completely filled with amyloid precursor protein granules.
      "Ghost"-like deposits of amyloid precursor protein granules arranged in
      pyramidal, plaque-like shapes were identified. We detected long, amyloid
      precursor protein-immunopositive neurites surrounding and entering plaques. Many
      contained swollen varicosities along their length or ended in bulbous tips.
      Amyloid precursor protein immunoreactivity in the Alzheimer's brain was primarily
      present as granular deposits (plaques). The amyloid precursor protein granules do
      not appear to co-localize within either astrocytes or microglia, as evidenced by
      double-labeling immunohistochemistry with anti-glial fibrillary acidic protein
      and anti-leukocyte common antigen antibodies or Rinucus cummunicus agglutin
      lectin. Amyloid precursor protein could occasionally be detected in blood vessels
      in Alzheimer's brains. The predominantly neuronal and neuritic localization of
      amyloid precursor protein immunoreactivity indicates a neuronal source for much
      of the amyloid precursor protein observed in Alzheimer's disease pathology, and
      suggests a time-course of plaque development beginning with neuronal amyloid
      precursor protein accumulation, then deposition into the extracellular space,
      subsequent processing by astrocytes or microglia, and resulting in beta-amyloid
      peptide accumulation in plaques.

PMID- 1378574
TI  - Aspiration lesions of rat ventral hippocampus disinhibit responding in
      conditioned suppression or extinction, but spare latent inhibition and the
      partial reinforcement extinction effect.
AB  - Latent inhibition refers to a decrement in learning about a stimulus as a result
      of its prior non-reinforced presentation. There is evidence that lesions of
      nucleus accumbens and conventional hippocampal lesions both disrupt the
      development of latent inhibition. The partial reinforcement extinction effect
      reflects the observation that resistance to extinction is normally greater in
      animals that have been rewarded on a 50% random proportion of acquisition trials
      than in those rewarded on every trial. Conventional hippocampal lesions,
      excitotoxic lesions of hippocampus plus subiculum, or conventional lesions of
      nucleus accumbens abolish this effect. The present experiments examined the
      possibility that a projection originating in the ventral [temporal in the
      nomenclature proposed by Blackstad: (1956) J. comp. Neurol. 105, 417-537]
      subiculum and terminating in nucleus accumbens underlies the normal development
      of latent inhibition and the partial reinforcement extinction effect, by
      evaluating the performance on these two behaviours of rats with aspiration
      lesions in the ventral hippocampal region. There was equally clear evidence of
      latent inhibition and of a partial reinforcement extinction effect in controls
      and in rats with ventral hippocampal damage. However, superimposed on this, the
      hippocampal lesion induced a loss of behavioural inhibition in both paradigms.
      Subsequent anatomical analyses indicated that cell bodies in nearby
      retrohippocampal cortex had maintained intact projections to nucleus accumbens.
      We suggest that these extra-hippocampal projections may underlie the ability to
      learn to ignore irrelevant stimuli.

PMID- 1378575
TI  - Grafted neostriatal neurons express a late-developing transient potassium
      current.
AB  - Previous anatomical and physiological studies of neostriatal grafts have
      suggested that transplanted neurons do not develop beyond an early postnatal
      stage. We have tested whether this hypothesis can be generalized by
      characterizing the developmentally regulated Ca-independent potassium currents in
      graft neurons. These currents were studied using a combination of the whole-cell
      voltage-clamp technique with acutely-dissociated neurons and intracellular
      recording in slices. In all of the graft neurons examined with voltage-clamp
      techniques (n = 13), evidence was found for a slowly-inactivating potassium
      current that is seen only beyond the third or fourth postnatal week in normal
      rats. A current resembling the delayed rectifier was also seen in all sample
      neurons. The rapidly inactivating A-current which dominates recordings from
      nearly all immature neurons was seen in only about half (54%, 7/13) of the graft
      neurons; in a sample of normal adult striatal neurons, the A-current was detected
      in a similar percentage of neurons (41%, 25/62). Recordings of graft neurons in
      slices corroborated the voltage-clamp findings in revealing a slowly inactivating
      outward current that acts in the subthreshold potential range. These findings
      suggest that graft neurons express the normal complement of depolarization
      activated potassium channel proteins seen in adult neurons.

PMID- 1378578
TI  - The organization of the crossed geniculogeniculate pathway of the rat: a
      Phaseolus vulgaris-leucoagglutinin study.
AB  - The intergeniculate leaflet of the thalamus is known to give rise to neuronal
      projections to the suprachiasmatic nuclei and the rostral part of the pineal
      gland. Via these projections the intergeniculate leaflet is considered to play a
      role in regulation of circadian rhythms. Iontophoretic injections of the
      anterograde tracer Phaseolus vulgaris-leucoagglutinin were placed in various
      subnuclei of the lateral geniculate nucleus in order to study the topographical
      organization of the crossed geniculogeniculate pathway in the rat. Injections
      involving neurons in the intergeniculate leaflet or the medial subpart of the
      ventral nucleus (which presumably is part of the intergeniculate leaflet of the
      thalamus too) gave rise to labeled nerve fibers in the opposite lateral
      geniculate nucleus. The axons contained in this pathway were followed either
      medially via the posterior commissure, or via the optic tracts and optic chiasm,
      to the contralateral hemisphere. In the contralateral lateral geniculate nucleus,
      the intergeniculate leaflet was most densely innervated, but a substantial
      innervation of the ventral lateral geniculate nucleus was observed as well. Only
      a few labeled fibers were observed in the dorsal subnucleus. However, the dense
      innervation of the contralateral intergeniculate leaflet not only covered the
      small zone between the dorsal and ventral nuclei, but also a dorsomedial part of
      the ventral nucleus that merged caudally with the lateral part of the zona
      incerta. In the remaining part of the ventral nucleus, single Phaseolus vulgaris
      leucoagglutinin-labeled fibers surrounded specific cells. The demonstration of a
      divergent projection between the intergeniculate leaflet and specific subparts of
      the contralateral geniculate nuclei indicates that the two lateral geniculate
      nuclei are regulating each other. The function of this pathway is suggested to be
      related to the regulation of circadian rhythmicity, but experimental evidence for
      this hypothesis is still lacking.

PMID- 1378576
TI  - Increased dopamine release in vivo in nucleus accumbens and caudate nucleus of
      the rat during drinking: a microdialysis study.
AB  - Changes in dopamine release and metabolism during drinking in thirsty rats were
      studied using in vivo microdialysis. Animals were maintained on controlled water
      (1 h per day) and trained to lick for water in a behavioural box. Microdialysis
      probes were then inserted into the left nucleus accumbens and right caudate
      nucleus through previously implanted guide cannulae, and the following day
      animals were connected for dialysis perfusion, during which they were allowed 1 h
      free access to water. Dopamine, and its metabolites, 3,4-dihydroxyphenylacetic
      acid and homovanillic acid, increased in both nucleus accumbens and caudate
      nucleus in association with drinking, but the 5-hydroxytryptamine metabolite, 5
      hydroxyindoleacetic acid, only increased in the caudate nucleus. There was a
      direct correlation between the maximum dopamine release in nucleus accumbens and
      the maximum licking rate per 10-min period, but the maximum increase in dopamine
      did not occur until after the period of maximum licking. Increases in 3,4
      dihydroxyphenylacetic acid and homovanillic acid were further delayed (by 20 and
      30 min, respectively). In the caudate, changes in 5-hydroxyindoleacetic acid
      showed a very similar time-course to those of 3,4-dihydroxyphenylacetic acid.
      These data show that dopamine systems in both nucleus accumbens and caudate
      nucleus are activated in relation to drinking in thirsty rats. In addition, they
      indicate that 5-hydroxytryptamine systems in the caudate nucleus, but not in
      nucleus accumbens, may also be involved. The support that the results provide for
      the hypothesized connection between reward and limbic dopamine is discussed.

PMID- 1378577
TI  - Enhancement of tonic and phasic events of rapid eye movement sleep following
      bilateral ibotenic acid injections into centralis lateralis thalamic nucleus of
      cats.
AB  - The excitotoxin ibotenic acid (1.2-2.6 microliters of 50 micrograms/microliters)
      was injected bilaterally into the thalamic centralis lateralis nucleus of
      chronically implanted cats in order to study the effects of tonic excitation
      followed by destruction of perikarya on the sleep-waking cycle and its
      electrographic correlates. Ibotenate injections were performed under mild
      ketamine anaesthesia. Immediately afterwards, the animals showed behavioural
      arousal accompanied first by ocular nystagmiform movements and then by
      pontogeniculooccipital waves. By 6-10 h post-injection, the numbers of rapid eye
      movement sleep episodes, but not their duration, increased compared to the
      preinjection control period. The injection sites were histologically confirmed
      using conventional Thionin stains. Additional control was provided by retrograde
      transport of wheat-germ agglutinin conjugated with horseradish peroxidase. The
      present results suggest that a population of neurons important for ocular
      saccades, pontogeniculooccipital waves, and the state of desynchronized sleep is
      present in the internal medullary lamina, in particular in the centralis
      lateralis nuclei.

PMID- 1378581
TI  - [Interpretation of laboratory data related to the determination of tumor
      markers].
AB  - The Authors consider the quantity of CEA-AFP-MCA-CA 125 measurements performed by
      their laboratory during ten months in 1989-90: 1.000 for CEA, 500 for AFP, 52 for
      MCA, 36 for CA 125. The observation of scarce significance (especially for CEA
      and AFP) has, in this case, only a statistical sense, depending on the unknown
      motivation of the analysis requests. They also observe greater significance of
      MCA and CA 125 measurements, and they underline the necessity to correlate
      requests, clinical situations and results, according on their peculiar purpose:
      to verify the reliability of the demands in order to value the validity of the
      markers, avoiding useless and not specific data for a better monitoring of the
      neoplastic patient.

PMID- 1378580
TI  - Acetylcholinesterase-containing neurons, substance P and enkephalin fibers in the
      ventral horns of developing human embryos and fetuses.
AB  - The presence of the acetylcholinesterase neurons and substance P-like and
      enkephalin-like fibers in the various nuclear columns of the ventral horns of the
      spinal cords was studied in the developing human by acetylcholinesterase
      histochemistry and substance P and enkephalin immunohistochemistry.
      Acetylcholinesterase-positive neurons initially appeared in the lateral neuronal
      columns and eventually were also observed in the medial columns as well as the
      median columns at various levels of the spinal cord by 10 weeks' gestation.
      Acetylcholinesterase-positive neurons in the lower sacral levels were not
      detected until 11-12 weeks' gestation. Diffused substance P- and enkephalin-like
      fibers were demonstrated as early as 10 weeks' gestation but did not align with
      any particular nuclear column until after 15 weeks' gestation. These fibers
      further increased in length and adopted reticular branching patterns and many of
      these tended to surround the cell bodies of the nuclear columns. Possible
      interaction of acetylcholinesterase neurons and substance P and enkephalin fibers
      would commence by 15 weeks' gestation.

PMID- 1378579
TI  - Distribution of neurokinin B in rat spinal cord and peripheral tissues:
      comparison with neurokinin A and substance P and effects of neonatal capsaicin
      treatment.
AB  - In the present study, highly specific radioimmunoassays were developed and used
      to measure neurokinin B, neurokinin A and substance P in the rat spinal cord and
      various peripheral tissues. The results are as follows. (1) Neurokinin B and
      neurokinin A were distributed all along the rostrocaudal axis of the spinal cord,
      as is substance P, and were more concentrated in the dorsal than in the ventral
      region. (2) Substance P was more abundant in the central and peripheral nervous
      tissues than neurokinin A, while in certain peripheral organs, neurokinin A was
      more abundant than substance P. In the spinal cord, neurokinin B concentrations
      were lower than those of the other two tachykinins. (3) In contrast to neurokinin
      A and substance P, neurokinin B was not detected in any of the peripheral tissues
      examined. (4) Capsaicin treatment reduced by half neurokinin A and substance P
      concentrations in the dorsal region of the spinal cord, the dorsal root ganglia
      and the sciatic nerve, but was without effect on neurokinin B concentrations in
      the spinal cord. Neurokinin A, like substance P, may therefore have an important
      function in the transmission of sensory information, particularly in nociceptive
      transmission from the periphery to the spinal cord and in peripheral neurogenic
      inflammation. In contrast, since neurokinin B was not found in the sensory
      neurons, it is not likely to have these functions, but may perhaps control them.

PMID- 1378583
TI  - Surgical management of subfoveal choroidal neovascularization.
AB  - BACKGROUND: Subfoveal choroidal neovascularization (CNV) usually is associated
      with a poor visual prognosis. Laser photocoagulation of certain subfoveal
      membranes secondary to age-related macular degeneration (ARMD) appears preferable
      to observation based on recent Macular Photocoagulation Study (MPS) findings but
      is associated with decreased vision. The authors explored the use of
      vitreoretinal surgical techniques as an alternative method of eradicating
      subfoveal CNV. METHODS: After vitrectomy, a small retinotomy technique was used
      to extract or disconnect from the choroidal circulation subfoveal CNV in 58 eyes.
      There were 33 eyes with ARMD, 20 eyes with presumed ocular histoplasmosis, and 5
      eyes with miscellaneous etiologies. Five eyes also received subfoveal RPE
      patches. RESULTS: With limited follow-up, significant improvement in vision
      (defined as 2 Snellen lines) was achieved in 7 of 22 eyes with ARMD CNV removal
      (1 eye 20/20), 0 of 4 eyes with ARMD CNV removal and RPE patches, and 1 of 7 eyes
      with ARMD CNV disconnection. Significant improvement was achieved in 6 of 16 eyes
      with presumed ocular histoplasmosis removal and 0 of 4 eyes with presumed ocular
      histoplasmosis CNV disconnection. In 5 eyes with miscellaneous CNV, 2 improved
      (20/20 and 20/40). CNV recurred in 29%. CONCLUSIONS: Some patients with subfoveal
      CNV appear to benefit from surgical removal. Only rarely do eyes with ARMD
      improve. Longer-term follow-up and refined case selection are required before
      this approach can be widely recommended.

PMID- 1378586
TI  - Interferon and natural killer cell activity in patients with exanthem subitum.
AB  - Early immune response was studied by assessing interferon (IFN) and natural
      killer cell activity in 13 patients with exanthem subitum associated with human
      herpesvirus 6 infection during the acute and convalescent phases. Only IFN-alpha
      showed a significant increase in the plasma of patients during the acute febrile
      phase compared with the convalescent period. The inhibitory effect of IFN-alpha
      and IFN-beta on human herpesvirus 6 replication was demonstrated in vitro with
      cord blood mononuclear cells. Natural killer cell activity was also significantly
      augmented in the acute phase, especially in the exanthem period, rather than in
      the convalescent phase (P less than 0.01). These results suggest that the
      enhanced IFN-alpha response and natural killer cell activity in the acute early
      phase of the disease may play pivotal roles in the recovery from exanthem
      subitum.

PMID- 1378584
TI  - [Pathogenesis, therapy, prevention and prognosis in chronic viral hepatitis].
AB  - The paper deals with the pathogenesis, therapy, prophylaxis and prognosis of
      three chronic viral hepatitides type B, C and Delta. The immunologic and
      virological processes that play a role in the development of chronicity or
      progression, furthermore, factors influencing the therapeutic responses are
      discussed in details. Until now various antiviral and immunomodulatory agents
      were administered in chronic type B hepatitis, recently the most promising
      results were reported using recombinant interferons. The importance of the
      prevention, with special regard to the vaccination with HBsAg-vaccine is briefly
      summarized. The treatment and prophylaxis of chronic type C hepatitis is not
      resolved yet, interferon may be effective only a part of cases. The therapy of
      Delta virus related chronic hepatitis means a major problem as well.

PMID- 1378585
TI  - Multiple src-related kinase genes, srk1-4, in the fresh water sponge Spongilla
      lacustris.
AB  - In one of the simplest metazoan organisms, the sponge Spongilla lacustris, at
      least four different src-related kinase genes (srk1-4) are expressed, all of
      which show a high degree of similarity to the c-src genes of vertebrates. Whereas
      srk2 and srk3 are clearly unrelated at the nucleic acid level, srk1 and srk4
      share identical sequences in the 5' parts of their cDNAs. The cloning of several
      primer extension clones and genomic polymerase chain reaction experiments
      confirmed the hypothesis of an alternative splicing of tandemly arranged carboxy
      terminal parts of srk1 and srk4. The genomic sequence encoding both proteins was
      found to be interrupted at the splice point by an intron which is located in the
      same position as one of the introns in the chicken src gene, which is the only
      gene conserved in invertebrates and vertebrates. All four srk genes are expressed
      in adult sponges as mRNA transcripts of about 2.2 kb. Tyrosine kinase activity of
      a src-related kinase could be detected in adult sponges but not in their resting
      form (gemmulae), and may reflect the activity of the srk protein products.
      Spongilla lacustris is the simplest organism from which a protein tyrosine kinase
      gene has been isolated. The presence of at least four such genes in the
      evolutionary ancient and primitive phylum Porifera suggests that tyrosine kinase
      genes arose concomitantly with or shortly after the appearance of multicellular
      organisms and that their activity may be involved in aggregation and cell-cell
      recognition.

PMID- 1378582
TI  - Iris neovascularization in proliferative vitreoretinopathy.
AB  - PURPOSE: The purpose of this study is to report on the prevalence, incidence, and
      associated risk factors of iris neovascularization in nondiabetic patients
      undergoing vitrectomy for retinal detachment complicated by proliferative
      vitreoretinopathy (PVR). METHODS: The authors conducted a retrospective review of
      141 consecutive non-diabetic patients undergoing vitrectomy for recurrent retinal
      detachment resulting from PVR. Univariate and multivariate analyses were
      performed on all patients to determine which preoperative, intraoperative, and
      postoperative factors were associated with the development of postoperative iris
      neovascularization. RESULTS: Twenty-seven of the 141 (19%) patients were noted
      with preoperative and/or postoperative iris neovascularization. Four of eight
      patients presenting with preoperative iris neovascularization had complete
      regression after successful reattachment of the retina. Results of analysis of
      the remaining 133 patients without iris neovascularization preoperatively showed
      residual retinal detachment as the most significant risk factor for postoperative
      iris neovascularization. In the absence of panretinal photocoagulation, none of
      the 27 patients developed neovascular glaucoma. CONCLUSIONS: The development of
      iris neovascularization preoperatively or post-operatively is not necessarily a
      predictor of a poor anatomic and/or visual result. Iris neovascularization in PVR
      rarely if ever progresses to neovascular glaucoma. Panretinal photocoagulation is
      not indicated in these patients. Retinal reattachment is the most important
      factor in the prevention and/or resolution of postoperative iris
      neovascularization. The development of iris neovascularization in PVR appears to
      be a multifactorial process requiring multiple variables acting in concert.

PMID- 1378587
TI  - Potassium currents of rat basilar artery smooth muscle cells.
AB  - Primary isolates of smooth muscle cells from the basilar artery of the rat were
      studied using whole-cell and single-channel patch-clamp techniques. Two distinct
      potassium currents were characterized. With low intracellular calcium,
      depolarization above 0 mV elicited an outward current of a few hundred pA (at
      +120 mV) with sigmoidal onset and little inactivation during 1.25 s steps. This
      current was reduced by bath application of 1 mM procaine or 1 mM strychnine, but
      not by 500 nM charybdotoxin. These are characteristics of the delayed rectifier
      potassium current in other preparations. With higher intracellular calcium,
      depolarization above 0 mV elicited a non-inactivating potassium current of
      several nA (at +120 mV). This current persisted in the presence of 1 mM procaine
      or strychnine but was reduced by bath application of 100 nM charybdotoxin. In
      whole-cell recordings in which intracellular calcium was unbuffered with EGTA,
      spontaneous transient outward currents were manifest and displayed voltage
      dependence and tail currents similar to the calcium-dependent current. The
      spontaneous transient current and the calcium-dependent current had similar
      sensitivity to charybdotoxin. Cell-free membrane patches contained one or more
      channels of 220 pS (in solutions symmetrical with respect to potassium) with
      similar voltage and calcium dependence. These are characteristics of the large
      conductance calcium-activated potassium current in other preparations.

PMID- 1378588
TI  - Kinetic and pharmacological properties of high- and low-threshold calcium
      channels in primary cultures of rat hippocampal neurons.
AB  - The kinetic, permeability and pharmacological properties of Ca currents were
      investigated in primary cultures of rat hippocampal neurons. The low-voltage
      activated (LVA) Ca current turned on positive to -60 mV and fully inactivated in
      a voltage-dependent way. This current was depressed by nickel (Ni, 40 microM) and
      amiloride (500 microM) and was insensitive to omega-conotoxin (omega-CgTx) (4
      microM) and to the Ca agonist Bay K 8644 (5 microM). The high-voltage-activated
      (HVA) Ca current turned on positive to -40 mV and inactivated slowly and
      incompletely. This current was much less sensitive than the LVA current to Ni and
      amiloride but more sensitive to cadmium. omega-CgTx blocked only partially this
      current (about 50%) in an irreversible way. Bay K 8644 had a clear agonistic
      action almost exclusively on the omega-CgTx-resistant HVA current component. The
      present results suggest that the HVA channels, quite homogeneous for their
      kinetic properties and sensitivity to holding potentials, can be
      pharmacologically separated in two classes: (i) omega-CgTx-sensitive and Bay-K
      8644-insensitive (omega-S/BK-I) and (ii) omega-CgTx-insensitive and Bay-K-8644
      sensitive (omega-I/BK-S), the latter displaying a stronger Ca-dependent
      inactivation.

PMID- 1378590
TI  - Nucleotide sequences of 16S rRNA encoding genes from halophilic archaea
      Halococcus morrhuae NRC16008 and Haloferax mediterranei ATCC33500.

PMID- 1378592
TI  - Holter documented sudden death in a patient with an implanted defibrillator.
AB  - A 68-year-old man with recurrent attacks of monomorphic ventricular tachycardia
      (VT) received a pacer cardioverter defibrillator featuring antitachycardia pacing
      and cardioversion/defibrillation. Over 300 episodes of VT were successfully
      terminated by antitachycardia pacing. During Holter monitoring the patient
      experienced supraventricular tachycardia with delivery of multiple
      antitachycardia pacing, cardioversion, and defibrillation therapies ending with
      the death of the patient. The following factors played a role in the unfortunate
      outcome of this patient: 1. triggering of VT therapy by an unexpected high sinus
      rate; 2. atrial fibrillation induced by cardioversion therapy; 3. a gradual and
      continuous increase in rate during atrial fibrillation possibly caused by
      repeated VT and ventricular fibrillation therapies and/or by a thrombus, found at
      autopsy, in a bypass graft; and 4. the limited ability of presently available
      defibrillators to distinguish between ventricular and supraventricular
      arrhythmias.

PMID- 1378591
TI  - Analysis of local electrogram characteristics correlated with successful
      radiofrequency catheter ablation of accessory atrioventricular pathways.
AB  - Due to the limited myocardial lesions produced by radiofrequency current, the
      ablation of accessory pathways (AP) requires precise localization of such
      connections. The purpose of this study was to ascertain which characteristic(s)
      of the local bipolar electrogram, recorded from the ablation and adjacent
      electrode immediately prior to the application of radiofrequency current,
      correlated with precision in localization adequate to permit AP ablation. Signal
      analysis was performed for 326 sets of electrograms preceding the attempted
      ablation of 107 APs in 100 consecutive patients. For 80 antegrade APs, the
      following variables were evaluated: (1) the presence or absence of an AP
      potential; (2) the local atrial-AP interval; (3) the local atrioventricular (AV)
      interval; and (4) the relationship between the onset of local ventricular
      depolarization and onset of delta wave of the surface electrocardiogram. For the
      27 concealed APs, the following characteristics were evaluated: (1) the presence
      or absence of an AP potential; and (2) the local VA interval during reciprocating
      tachycardia or ventricular pacing. RESULTS: Antegrade APs: By statistical
      analysis, the best correlate of successful ablation of an antegrade AP was a
      local AV interval less than or equal to 40 msec (positive predictive value = 94%;
      95% confidence intervals [CI] = 81%-100%). Local AV intervals less than or equal
      to 50 msec preceded 88% of successful AP ablations, compared to only 8% of failed
      radiofrequency current applications. The positive predictive value of the other
      variables were: presence of an AP potential: 35% (95% CI = 27%-40%); local atrial
      AP intervals less than or equal to 40 msec: 54% (95% CI = 43%-66%); and local
      ventricular depolarization preceding onset of the delta wave 43% (95% CI = 34%
      52%). For concealed APs, the positive predictive value of a VA interval less than
      60 msec was 71% (95% CI = 48%-88%); the positive predictive value for the
      presence of an AP potential was 58% (95% CI = 32%-81%). CONCLUSIONS: No single
      electrogram characteristic had a positive predictive value and a sensitivity
      greater than 90% for AP localization adequate for radiofrequency current
      ablation. For antegrade APs, the best correlate of adequate localization was a
      local AV interval less than or equal to 40 msec; as a corollary, radiofrequency
      current applications at sites where the local AV was greater than 60 msec, were
      unlikely to be effective. Objective criteria for the localization of concealed
      APs were less certain. Electrogram analysis, as a guide to AP localization and
      ablation, requires careful analysis of multiple variables, with analysis of the
      local AV interval a salient objective factor.

PMID- 1378589
TI  - Origin of the Alu family: a family of Alu-like monomers gave birth to the left
      and the right arms of the Alu elements.
AB  - The Alu dimeric elements are a common feature of the primate genomes, where they
      constitute a family of related sequences (1). The identification of a free left
      Alu monomer (FLAM) family plus a free right Alu monomer (FRAM) family suggests
      that the dimeric structure results from the fusion of a FLAM sequence with a FRAM
      sequence (2). Here, we describe a very old Alu-like monomeric family, referred to
      as FAM for fossil Alu monomer. This family arose from a 7SL RNA sequence and gave
      birth to the FLAM and FRAM families. From the results obtained, the evolution of
      the Alu family can be subdivided into two phases. The first phase, which involves
      only monomeric elements, is characterized by deep remodelling of the progenitor
      sequences and ends with the appearance of the first Alu dimeric element through
      the fusion of a FLAM and a FRAM element. The second phase, still in progress,
      starts with the first Alu dimeric element. This phase is characterized by the
      stabilization of the progenitor sequences.

PMID- 1378596
TI  - Electrophysiological abnormalities of the atrial muscle in patients with manifest
      Wolff-Parkinson-White syndrome associated with paroxysmal atrial fibrillation.
AB  - We investigated the electrophysiological properties of the atrial muscle in 33
      patients with manifest Wolff-Parkinson-White syndrome. Group I consisted of 13
      patients with paroxysmal atrial fibrillation and group II consisted of 20
      patients without paroxysmal atrial fibrillation. The anterograde and retrograde
      effective refractory periods of the accessory pathway and the inducibility of
      atrioventricular reciprocating tachycardia were not significantly different
      between the two groups. Endocardial electrograms, obtained by right atrial
      catheter mapping, were recorded during sinus rhythm from 12 sites of the right
      atrium in 12 of the 13 group I patients and in all group II patients. An abnormal
      atrial electrogram was defined as 100 msec or longer in duration, and/or the
      occurrence of eight or more deflections. Ten (83%) of the 12 group I patients had
      abnormal atrial electrograms, while only two (10%) of the 20 group II patients
      had abnormal atrial electrograms, and the difference was significant (P less than
      0.01). Thirty-six (26%) of the total 139 electrograms obtained from 12 group I
      patients and two (1%) of the total 199 electrograms obtained from 20 group II
      patients fulfilled the criteria for an abnormal atrial electrogram, and the
      difference was significant (P less than 0.01). The fragmented atrial activity
      zone, interatrial conduction delay zone, and repetitive atrial firing zone
      obtained by right atrial extrastimulation were significantly wider in group I
      than in group II, respectively. It was concluded that electrical abnormalities of
      the atrial muscle may play an important role in the occurrence of paroxysmal
      atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

PMID- 1378594
TI  - Use of event markers during exercise testing to optimize morphology criterion
      programming of implantable defibrillator.
AB  - The present generation implantable defibrillator introduced on-line event markers
      that can be used to evaluate tachycardia detection in the electrophysiological
      testing mode. These markers were used to assess the appropriateness of
      programming the morphology criterion for detection of ventricular tachycardia.
      Twenty-one consecutive patients (19 men, 2 women) performed 29 bicycle exercise
      tests with real-time recording of the electrocardiogram and the event markers on
      a multichannel recorder. Mean ejection fraction was 29% (range 15%-69%). Seven
      patients were taking antiarrhythmic agents. Twelve patients satisfied the
      morphology criterion at rest (n = 1) or during exercise (group I), and nine
      patients did not (group II). One patient was excluded from analysis because of
      continuous ventricular pacing. Mean peak heart rate was 130 beats/min in group I
      and 125 beats/min in group II. No statistical differences existed between the
      groups in relation to cycle length of ventricular tachycardia and mode of
      induction of arrhythmia, QRS duration on the electrocardiogram, during native
      rhythm, amplitude and duration of defibrillation patch R wave, calculated duty
      cycle at peak heart rate, and number of discharges of the automatic implantable
      cardioverter defibrillator at 2 to 14 months of follow-up time. It is concluded
      that clinical, electrocardiographic, and implantation data are unreliable in
      predicting satisfaction of the morphology criterion during high heart rates in
      native rhythm. Formal exercise testing in the electrophysiological mode enables a
      rational decision to be made about the appropriateness of the use of probability
      density function in each patient.

PMID- 1378597
TI  - Clinical significance of QRS duration during ventricular pacing.
AB  - To clarify the clinical significance of an abnormally prolonged paced QRS
      duration, we studied 114 patients who had undergone pacing for atrioventricular
      block (AVB). Patients were divided into two groups: group I consisted of 29
      patients with at least one paced QRS duration greater than or equal to 180 msec
      during the follow-up period; group II consisted of 85 patients with paced QRS
      durations less than 180 msec. The clinical background, QRS complexes before
      pacing, and the echocardiographic findings were assessed. Males (P less than
      0.05), those with H-V block (P less than 0.05) and a wider QRS complex of
      conducted and escape beats (both P less than 0.01) were dominant in group I. The
      incidence of underlying heart disease was greater in group I than in group II
      (83% vs 32%, P less than 0.01). Reduced left ventricular ejection fraction (LVEF)
      and increased left ventricular end-diastolic dimension (LVDd) were more prominent
      in group I than in group II (LVEF 0.49 +/- 0.17 vs 0.68 +/- 0.10, P less than
      0.01, LVDd 57.1 +/- 7.9 mm vs 48.5 +/- 5.6 mm, P less than 0.01). The paced QRS
      duration correlated with LVEF (r = -0.61) and LVDd (r = 0.81). A paced QRS
      duration greater than or equal to 180 msec was sensitive and specific for a LVEF
      less than 0.5 (83.3% and 85.2%) and LVDd greater than or equal to 60 mm (100% and
      81.4%). We conclude that patients with a prolonged paced QRS duration have more
      serious heart disease, and the paced QRS duration can be a useful indicator of
      impaired LV function.

PMID- 1378595
TI  - A multicenter experience with a bipolar tined polyurethane ventricular lead.
AB  - A multicenter study was undertaken to determine the failure rate of a specific
      polyurethane bipolar tined pacing lead, the Medtronic 4012 pacing lead. Six
      centers in the United States and Canada implanted 1,190 Medtronic 4012 pacing
      leads. The study was designed to determine the probability and clinical
      manifestations of lead failure. Only failures compatible with an insulation
      problem were included. The probability of a 4012 lead failure by Kaplan-Meier
      analysis was 20.9% at 6 years after implantation. Failures were manifested as
      sensing abnormalities, failure to capture, early battery depletion, and
      significant decrease in measured impedance compared with the previous impedance
      measurements. Of the 95 definite lead failures, 16 (16.8%) were associated with
      symptoms similar to those experienced before pacemaker placement. The observed
      failure rate is unacceptable, and strong consideration should be given to
      replacing the 4012 pacing lead in pacemaker-dependent patients and closely
      monitoring nondependent patients.

PMID- 1378593
TI  - Importance of recording the right bundle branch deflection in the diagnosis of
      His-Purkinje reentrant tachycardia.
AB  - Eight of 120 consecutive patients with inducible sustained ventricular
      tachycardia who were studied at our institution from September 1, 1988 to January
      1, 1991, were found to have reentry within the His-Purkinje System as the
      mechanism of their tachycardias. Two of the eight patients (25%) required the
      recording of the right bundle branch potential to elucidate the tachycardia
      circuits. The electrophysiological findings of these two patients are described.
      In both instances, the diagnosis of supraventricular tachycardia with aberrancy
      was excluded. In patient 1, a His-bundle electrogram preceded each QRS complex
      during tachycardia and the His-to-His interval variation preceded changes in QRS
      intervals. However, recordings from the right bundle branch allowed for exclusion
      of bundle branch reentry and evidence was found for reentry restricted to the
      left fascicles. In patient 2, despite instances of dissociation of the His-bundle
      deflection from the tachycardia, a right bundle branch potential preceded each
      QRS and spontaneous changes in the interval between successive activation of the
      right bundle branch preceded changes in ventricular activation. Catheter ablation
      of the right bundle branch eliminated the tachycardia. It is concluded that the
      recording of a right bundle branch potential should be included in
      electrophysiology study of patients in whom there is suspicion of reentry within
      the His-Purkinje System. Clinically, recognizing these forms of tachycardias can
      be important because they can be effectively treated with catheter ablation.

PMID- 1378600
TI  - "Medical computing".

PMID- 1378599
TI  - Arrhythmias in the mitral valve prolapse syndrome: clinical significance and
      management.

PMID- 1378601
TI  - Effect of radiofrequency (RF) catheter ablation on the function of permanent
      pacemakers.

PMID- 1378603
TI  - Rate modulated DDD (i.e., DDDR) pacing.

PMID- 1378602
TI  - Reimbursement for cardiac pacing.

PMID- 1378598
TI  - Retrograde supernormal conduction, gap phenomenon in concealed accessory
      atrioventricular pathways.
AB  - We present four patients with the Wolff-Parkinson-White syndrome who exhibited
      retrograde supernormal conduction or gap phenomenon in concealed accessory
      pathways. In the first patient, ventricular extrastimulus testing revealed
      retrograde block at the coupling interval of 520 msec and reappearance of
      conduction at the coupling interval of 370 msec. In a second patient, 1:1
      retrograde conduction was not present but supernormal conduction was demonstrated
      at coupling intervals of 360 msec to 310 msec during the ventricular
      extrastimulus testing when the basic drive consisted of atrioventricular (AV)
      simultaneous pacing. In a third patient, ventricular extrastimulus testing
      demonstrated retrograde conduction through the accessory pathway only at coupling
      intervals of 400 msec to 360 msec. In a fourth patient, retrograde block occurred
      at the coupling interval of 340 msec and retrograde "slow" conduction reappeared
      at coupling intervals of 300 msec to 250 msec (gap phenomenon) only when the
      basic drive consisted of AV simultaneous pacing. Thus, concealed accessory
      pathways may exhibit retrograde supernormal conduction or gap phenomenon.
      Ventricular extrastimulus testing consisting of AV simultaneous pacing during the
      basic drive may facilitate demonstration of these unusual properties.

PMID- 1378604
TI  - Lead failures.

PMID- 1378605
TI  - Performance of implantable cardiac rhythm management devices.

PMID- 1378611
TI  - Benign prostatic hyperplasia.

PMID- 1378606
TI  - Short-term reproducibility over time of right ventricular pulse pressure as a
      potential hemodynamic sensor for ventricular tachyarrhythmias.
AB  - The implantable cardioverter defibrillator (ICD) has been shown to effectively
      terminate episodes of ventricular tachyarrhythmias. Multiple investigators have
      suggested that the incorporation of hemodynamic sensors may allow ICDs to
      differentiate between hemodynamically unstable and stable ventricular
      tachyarrhythmias (VT), as well as differentiate ventricular from supraventricular
      tachycardias. Right ventricular (RV) pulse pressure has been shown to possess
      acceptable characteristics as a sensor for incorporation in ICDs. We sought to
      determine the short-term reproducibility of RV pulse pressure measurements by
      comparing RV pulse pressure measured during two separate episodes of VT in each
      of ten study patients. The mean VT cycle length for VT episode 1 was 293 +/- 15
      msec, and was 298 +/- 15 msec for VT episode 2 (P = NS). The decrease in mean
      arterial pressure was 40 +/- 7 mmHg in episode 1 and 37 +/- 7 mmHg in episode 2
      (P = NS). The decrease in RV pulse pressure during episode 1 was -13 +/- 2 mmHg,
      and -12 +/- 2 during episode 2 (P = NS). The decrease in RV pulse pressure during
      episodes of VT at two different times during a single electrophysiology study is
      highly reproducible, suggesting that RV pulse pressure may be a reliable sensor
      over time.

PMID- 1378608
TI  - Thermal ablation of perfused porcine left ventricle in vitro with the neodymium
      YAG laser hot tip catheter system.
AB  - Catheter ablation in the treatment of arrhythmias has been limited by the small
      lesion size achievable with a radiofrequency energy source. The feasibility of
      catheter ablation with a neodymium-yttrium-aluminum-garnet (Nd-YAG) laser hot tip
      catheter was tested because of the capability of achieving a high catheter-tissue
      contact temperature, which should result in a larger lesion. In a model of
      isolated perfused pig hearts, 77 endocardial lesions were produced with powers of
      1 to 10 watts and peak measured temperatures of 40 degrees to 318 degrees C.
      Lesion size correlated with power and temperature, but the correlations were
      poor. High temperature lesions resulted in significant intramyocardial catheter
      penetration and only marginal increased lesion width. Catheter ablation with a Nd
      YAG laser hot tip catheter is feasible, but carries a risk of perforation at high
      powers. High temperatures result in tissue dessication with a resultant fall in
      thermal conductivity that limits the radius of thermal injury and overall lesion
      size.

PMID- 1378610
TI  - Comparative evaluation of rate modulation in new generation evoked QT and
      activity sensing pacemakers.
AB  - Two new generation rate adaptive pacemakers, the Rhythmyx (Vitatron) using the
      evoked QT interval and the Legend (Medtronic) using vibration as indicators of
      metabolic demand, were compared for rate adaptive characteristics during
      different forms of exercise. While both showed improvements over previous
      generation pacemakers, they still show deficiencies in some aspects of rate
      modulation. Rhythmyx was slow to respond to changes in metabolic need and showed
      an "over-shoot" with increasing pacing rate on cessation of exercise. Legend was
      quick to adapt rate at beginning and end of exercise but showed a plateaus of
      rate modulation during the period of slowly increasing workload. Legend also
      showed only modest rate adaptation to changes in treadmill gradient and to
      bicycle ergometer exercise. Further developments in pacemaker technology are
      required if physiological rate adaptation to exercise is required.

PMID- 1378609
TI  - High and low strength nonsynchronized shocks given during canine ventricular
      tachycardia.
AB  - Cardioversion shocks given during ventricular tachycardia may cause ventricular
      fibrillation or acceleration of ventricular tachycardia, or arrest the
      tachycardia. A recently proposed theory may explain why the former two phenomena
      may occur. Briefly, this theory states that potential gradient shock fields of a
      critical strength delivered to tissue with a critical degree of refractoriness
      will cause circulating wave fronts of ventricular activation ("rotors") manifest
      as ventricular arrhythmia. We tested this theory by delivering nonsynchronized
      shocks 50% higher than defibrillation threshold or 50% lower than defibrillation
      threshold during 275 episodes of ventricular tachycardia in eight dogs with 5- to
      7-day-old myocardial infarcts. Shocks stronger than the defibrillation threshold
      are likely to create shock fields in the ventricles everywhere stronger than this
      critical value, and therefore would not generate rotors. Shocks less strong than
      the defibrillation threshold may create shock fields within the ventricles that
      include the critical value, and therefore cause rotors if given when critically
      refractory tissue is present. Nonsynchronized shocks were used to increase the
      likelihood of encountering tissue with a critical degree of refractoriness.
      Ventricular fibrillation or acceleration of ventricular tachycardia occurred
      following 83 of 138 (60%) low strength shocks and following 20 of 137 (14.6%)
      high strength shocks. The pooled odds ratio for induction of ventricular
      fibrillation or accelerated ventricular tachycardia after low strength shocks as
      compared to high strength shocks was 8.9. CONCLUSION: when given during
      ventricular tachycardia, low strength shocks are much more likely to cause
      ventricular fibrillation or accelerated ventricular tachycardia than are high
      strength shocks (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378612
TI  - Proline residues in transmembrane helices of channel and transport proteins: a
      molecular modelling study.
AB  - Proline residues are commonly found in putative transbilayer helices of many
      integral membrane proteins which act as transporters, channels and receptors.
      Intramembranous prolines are often conserved between homologous proteins. It has
      been suggested that such intrahelical prolines provide liganding sites for
      cations via exposure of the backbone carbonyl oxygen atoms of residues i-3 and i
      4 (relative to the proline). Molecular modelling studies have been carried out to
      evaluate this proposal. Bundles of parallel proline-kinked helices are considered
      as simplified models of ion channels. The energetics of K+ ion-helix bundle
      interactions are explored. It is shown that carbonyl oxygens exposed by the
      proline-induced kink and at the C-terminus of the helices may provide cation
      liganding sites. 'Hybrid' bundles of antiparallel helices, only some of which
      contain proline residues, are considered as models of transport proteins. Again,
      proline-exposed carbonyl oxygens are shown to be capable of liganding cations.
      The roles of alpha-helix dipoles and of the geometry of helix packing are
      considered in relation to cation-bundle interactions. Implications with respect
      to modelling of ion channel and transport proteins are discussed.

PMID- 1378607
TI  - Unusual Wenckebach upper rate response of an atrial-based DDD pacemaker.
AB  - We describe in this report an unusual form of Wenckebach upper rate response
      produced by a DDD pulse generator with atrial-based lower rate timing. The
      pacemaker maintained the programmed upper and lower rate intervals at the expense
      of a prolonged atrial paced-ventricular paced AV interval. This form of upper
      rate behavior eliminated the longer cycle (containing the unsensed P wave) that
      occurs at the end of the pacemaker Wenckebach sequence during traditional DDD
      pacing with ventricular-based lower rate timing.

PMID- 1378613
TI  - Structure of a 16 kDa integral membrane protein that has identity to the putative
      proton channel of the vacuolar H(+)-ATPase.
AB  - A 16 kDa protein has been isolated in a homogeneous form as the major component
      of a paracrystalline paired membrane structure closely resembling the gap
      junction. The primary structure of this protein from arthropod and vertebrate
      species has been determined by protein and cDNA sequencing. The amino acid
      sequences are highly conserved and virtually identical to the amino acid sequence
      of the proteolipid subunit of the vacuolar H(+)-ATPases. The disposition of the
      protein in the membrane has been studied using proteases and the N,N'
      dicyclohexylcarbodiimide reactive site identified. These data, together with
      secondary structure predictions, suggest that the 16 kDa protein is for the most
      part buried in the membrane, arranged in a bundle of four hydrophobic alpha
      helices. Using computer graphics, a model has been constructed based on this
      arrangement and on the electron microscopic images of the paracrystalline arrays.

PMID- 1378614
TI  - Laser desorption studies of high mass biomolecules in Fourier-transform ion
      cyclotron resonance mass spectrometry.
AB  - Matrix-assisted laser desorption ionization is used to obtain Fourier-transform
      ion cyclotron resonance mass spectra of model peptides (e.g., gramicidin S,
      angiotensin I, renin substrate, melittin, and bovine insulin). Matrix-assisted
      laser desorption ionization yields ions having appreciable kinetic energies. Two
      methods for trapping the high kinetic energy ions are described: (i) the ion
      signal for [M+H]+ ions is shown to increase with increasing trapping voltages,
      and (ii) collisional relaxation is used for the detection of [M+H]+ ions of
      bovine insulin.

PMID- 1378616
TI  - In vivo production of a stable single-stranded cDNA in Saccharomyces cerevisiae
      by means of a bacterial retron.
AB  - Gram-negative bacteria such as Myxococcus xanthus, Stigmatella aurantiaca, and
      Escherichia coli contain retroelements called retrons. Retrons consist of the msr
      msd region and the gene for reverse transcriptase (RT), which are essential for
      the production of the branched RNA-linked ms-DNA (multicopy single-stranded DNA).
      In this study, we attempted to produce msDNA in the yeast Saccharomyces
      cerevisiae. Retron Ec67 from E. coli, which is responsible for the production of
      msDNA-Ec67, was cloned under the GAL10 promoter in a 2-microns-based plasmid.
      msDNA thus produced was detected by extending the 3' end of the msDNA by avian
      myeloblastosis virus RT. This yielded a main product of 117 nucleotides.
      Treatment of this product with RNase A resulted in a DNA of 105 nucleotides.
      These results are in good agreement with the structure of msDNA-Ec67. The
      production of msDNA-Ec67 was further confirmed by Southern blot hybridization.
      The msDNA production was dependent upon the bacterial RT gene in the clone and
      was increased severalfold when the RT gene of retron Ec67 was placed in front of
      the msr-msd region. The potential of msDNA as a eukaryotic vector producing a
      stable single-stranded DNA as well as RNA is discussed.

PMID- 1378615
TI  - Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.
AB  - A number of lines of evidence suggest that cross-talk exists between the cellular
      signal transduction pathways involving tyrosine phosphorylation catalyzed by
      members of the pp60c-src kinase family and those mediated by guanine nucleotide
      regulatory proteins (G proteins). In this study, we explore the possibility that
      direct interactions between pp60c-src and G proteins may occur with functional
      consequences. Preparations of pp60c-src isolated by immunoprecipitation
      phosphorylate on tyrosine residues the purified G-protein alpha subunits (G
      alpha) of several heterotrimeric G proteins. Phosphorylation is highly dependent
      on G-protein conformation, and G alpha(GDP) uncomplexed by beta gamma subunits
      appears to be the preferred substrate. In functional studies, phosphorylation of
      stimulatory G alpha (G alpha s) modestly increases the rate of binding of
      guanosine 5'-[gamma-[35S]thio]triphosphate to Gs as well as the receptor
      stimulated steady-state rate of GTP hydrolysis by Gs. Heterotrimeric G proteins
      may represent a previously unappreciated class of potential substrates for pp60c
      src.

PMID- 1378617
TI  - Identification of Tyr-185 as the site of tyrosine autophosphorylation of
      recombinant mitogen-activated protein kinase p42mapk.
AB  - Tyrosine phosphorylation of 42-kDa mitogen-activated protein kinase (p42mapk)
      occurs during expression of the recombinant protein in Escherichia coli, as well
      as during in vitro phosphorylation of the protein purified from this source.
      Structural analyses were performed to identify the site(s) of tyrosine
      phosphorylation of recombinant p42mapk, both during expression of the protein in
      E. coli and during in vitro incubations with ATP/Mg2+/Mn2+. Mass spectrometry and
      phosphopeptide mapping showed that tyrosine phosphorylation of recombinant
      p42mapk occurs on Tyr-185, the site of regulatory tyrosine phosphorylation that
      occurs in mitogen-stimulated mammalian cells.

PMID- 1378618
TI  - Epitope-specific suppression of antibody response in experimental autoimmune
      myasthenia gravis by a monomethoxypolyethylene glycol conjugate of a
      myasthenogenic synthetic peptide.
AB  - A synthetic peptide corresponding to a myasthenogenic region of Torpedo
      californica acetylcholine (AcCho) receptor (AcChoR) alpha subunit, AcChoR alpha
      (125-148), was conjugated to monomethoxypolyethylene glycol (mPEG). Injection of
      mice with the mPEG-AcChoR alpha-(125-148) conjugate and subsequent immunization
      with whole Torpedo AcChoR suppressed the development of experimental autoimmune
      myasthenia gravis (EAMG) by electrophysiological criteria. In anti-AcChoR sera
      from these animals, the antibody response against unconjugated AcChoR alpha-(125
      148) was decreased, while the antibody responses against whole AcChoR and other
      epitopes were not altered. There were no detectable changes in T-cell
      proliferation responses to AcChoR alpha-(125-148) or to whole AcChoR in these
      animals. Prior injections with a "nonsense" peptide-mPEG conjugate had no effect
      on responses to the subsequent immunization with whole Torpedo AcChoR. The
      results indicate that the mPEG-AcChoR alpha-(125-148) conjugate has epitope
      specific tolerogenicity for antibody responses in EAMG and that the AcChoR alpha
      subunit region comprising residues 125-148 plays an important pathophysiological
      role in EAMG. The epitope-directed tolerogenic conjugates may be useful for
      future immunotherapies of human myasthenia gravis. The strategy of specific
      suppression of the antibody response to a predetermined epitope by using a
      synthetic mPEG-peptide conjugate may prove useful in manipulation and suppression
      of unwanted immune responses such as autoimmunity and allergy.

PMID- 1378621
TI  - Adhesion is required for protein kinase C-dependent activation of the Na+/H+
      antiporter by platelet-derived growth factor.
AB  - Adhesion of normal, anchorage-dependent cells to a solid substratum leads to
      activation of the Na+/H+ antiporter and elevation of intracellular pH. These
      effects are mediated by extracellular matrix proteins, such as fibronectin, and
      their receptors, the integrins. Experiments using pharmacological inhibition and
      down-regulation of protein kinase C (PKC) in C3H 10T1/2 cells show that platelet
      derived growth factor induces activation of the Na+/H+ antiporter by means of a
      PKC-dependent pathway in adherent cells but cannot do so in poorly adherent
      cells. Poorly adherent cells are, however, able to elevate intracellular pH in
      response to a phorbol ester, indicating that PKC and subsequent steps in the
      pathway are functional. These results indicate that coupling of platelet-derived
      growth factor to PKC activation requires cell adhesion.

PMID- 1378619
TI  - Detection of rare antigen-presenting cells by the lacZ T-cell activation assay
      suggests an expression cloning strategy for T-cell antigens.
AB  - The alpha/beta T-cell receptor a complex ligand formed by the association of
      antigenic peptides with molecules of the major histocompatibility complex (MHC).
      The inherent limitations of the conventional T-cell activation assays used to
      detect these peptide/MHC ligands have, until now, hampered the development of
      expression cloning systems for T-cell antigens. To overcome these limitations, we
      have recently introduced a method for detecting ligand-induced activation of
      individual T cells. This assay, which makes use of a lacZ reporter construct,
      differs from conventional ligand-induced activation assays in that it allows the
      detection of single, activated T cells in large pools of resting cells. We
      applied the lacZ assay to the problem of screening expression libraries, which
      requires the ability to detect ligand-bearing antigen-presenting cells when they
      are present at very low frequency. We show here that ligand-expressing antigen
      presenting cells can be detected at frequencies of 1:10(3)-10(4), a level of
      sensitivity compatible with the screening of cDNA libraries. Furthermore, by
      using as antigen-presenting cells COS-7 cells stably transfected with the murine
      Kb class I MHC molecule, we demonstrate that transiently expressed ovalbumin is
      efficiently processed and presented to an ovalbumin/Kb-specific T-cell hybridoma.
      lacZ expression is induced in a detectable number of cocultured T cells, even
      when the ovalbumin cDNA consists of only 1:10(4) of the total DNA used to
      transfect the COS cells. These results suggest that unknown T-cell antigens may
      be identified by screening cDNA libraries in MHC-expressing COS cells using lacZ
      inducible T cells as indicators of peptide antigen expression.

PMID- 1378623
TI  - Inhibition of human immunodeficiency virus activity by phosphorodithioate
      oligodeoxycytidine.
AB  - Phosphorothioate oligodeoxynucleotides exert a sequence-independent
      cytoprotective effect against human immunodeficiency virus type 1 (HIV-1). We now
      report that phosphorodithioate-containing oligodeoxycytidines are very potent
      inhibitors of HIV-1 reverse transcriptase in vitro, as they exhibit an increasing
      inhibitory effect with length and number of phosphorodithioate internucleotide
      linkages. This inhibitory effect can be at least 30-fold greater with
      phosphorodithioate oligodeoxycytidine than for the corresponding phosphorothioate
      analog of similar length. In cell culture, phosphorodithioate oligodeoxycytidines
      are active inhibitors of syncytia formation and effectively inhibit de novo
      infection of target cells by HIV-1. Moreover, comparative experiments show that a
      deoxycytidine phosphorodithioate 14-mer is as effective an inhibitor of de novo
      infection as a phosphorothioate-containing 28-mer. Such potent inhibition by
      oligomers of relatively short length makes dithioate analogs an additional class
      of potential therapeutic agents against acquired immunodeficiency syndrome.

PMID- 1378622
TI  - Association of the erythropoietin receptor with protein tyrosine kinase activity.
AB  - We have examined the signal transduction mechanism of the hematopoietic growth
      factor erythropoietin (Epo). Epo stimulation of Ba/F3 cells transfected with the
      Epo receptor resulted in increases in tyrosine phosphorylation of proteins of 97,
      75, and 55 kDa. Epo-induced increases in tyrosine phosphorylation of a 97-kDa
      protein were also detected within the Epo receptor complex, suggesting that a
      protein tyrosine kinase is associated with the Epo receptor. Protein tyrosine
      kinase activity was found within the Epo receptor complex and modulation of this
      activity was observed after treatment of cells with Epo. Furthermore,
      constitutively high amounts of protein kinase activity were observed in Epo
      receptor complexes isolated from autonomously growing cells coexpressing the Epo
      receptor and the leukemogenic glycoprotein gp55. The dominant
      phosphotyrosylprotein found associated with the Epo receptor was 97 kDa. An Epo
      receptor-associated protein of identical molecular mass was also found to bind
      ATP, a characteristic critical for protein kinases. Collectively, these data
      demonstrate that the Epo receptor is associated with protein tyrosine kinase
      activity and further suggest that a 97-kDa phosphotyrosylprotein associated with
      the Epo receptor is a protein tyrosine kinase involved in Epo-mediated signal
      transduction.

PMID- 1378624
TI  - CD14 is involved in control of human immunodeficiency virus type 1 expression in
      latently infected cells by lipopolysaccharide.
AB  - Lipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1
      (HIV-1) long terminal repeat-directed transcription in transfected monocyte
      macrophage cell lines and dramatically increases HIV-1 production in the latently
      infected monocyte-macrophage-like cell line U1. This response to LPS, however,
      can only be observed after pretreatment of the U1 cells with granulocyte
      macrophage colony-stimulating factor (GM-CSF). CD14, the differentiation antigen
      that acts as a receptor for complexes of LPS and LPS-binding protein, is now
      demonstrated to be involved in LPS-induced stimulation of HIV-1 replication. CD14
      is shown to be expressed on a subpopulation of U1 cells only after treatment with
      GM-CSF and correlates with HIV-1 production stimulated by LPS. Importantly, only
      those U1 cells that express CD14 can be induced by LPS to upregulate HIV-1
      production. In addition, a monoclonal antibody directed against CD14 can block
      LPS-induced stimulation of HIV-1 production from these latently infected cells.

PMID- 1378626
TI  - Endothelial nitric oxide synthase: molecular cloning and characterization of a
      distinct constitutive enzyme isoform.
AB  - Nitric oxide (NO) is a ubiquitous intercellular messenger molecule synthesized
      from the amino acid L-arginine by NO synthases in diverse cells and tissues. NO
      is synthesized in vascular endothelial cells and appears to play an important
      role in the control of blood pressure and platelet aggregation. A detailed
      understanding of the regulation of NO synthesis by endothelial cells has been
      hampered by the lack of molecular clones for endothelial NO synthase; the
      isolation and characterization of such clones is reported herein. The
      constitutive NO synthases present in endothelial cells and in brain share common
      biochemical and pharmacologic features. We purified NO synthase from bovine brain
      and determined the amino acid sequence of several tryptic peptides. The sequence
      of the bovine brain peptides is nearly identical to the deduced amino acid
      sequence previously determined for the rat brain NO synthase. These sequence data
      were utilized to design PCR-generated NO synthase cDNA probes, which were used to
      isolate clones encoding NO synthase from a bovine aortic endothelial cell (BAEC)
      cDNA library. A full-length NO synthase cDNA clone was isolated, representing a
      protein of 1205 amino acids with a molecular mass of 133 kDa; transfection of
      this clone in a heterologous expression system demonstrated the expected
      enzymatic activity. The deduced amino acid sequence of the BAEC NO synthase cDNA
      differs at numerous residues from the sequence determined for the purified bovine
      brain protein and shows 50-60% sequence identity with recently isolated molecular
      clones for murine macrophage and rat brain NO synthase isoforms. Bovine genomic
      Southern blots probed with bovine brain and BAEC NO synthase cDNA probes identify
      distinct bands, indicating that these cDNAs are the products of different genes.
      Prolonged treatment of BAECs with the cytokine tumor necrosis factor alpha, which
      we have previously shown to result in a marked increase in NO synthase activity,
      is associated with a decrease in the abundance of the 4.8-kilobase BAEC NO
      synthase transcript. The increase in BAEC NO synthase activity induced by tumor
      necrosis factor alpha is thus likely to involve posttranscriptional mechanisms or
      the induction of a distinct endothelial NO synthase isoform.

PMID- 1378620
TI  - Synthesis of mannosylglucosaminylinositol phospholipids in normal but not
      paroxysmal nocturnal hemoglobinuria cells.
AB  - To identify mannosyl (Man)-containing intermediates of the human glycoinositol
      phospholipid (GPI) anchor pathway and examine their expression in paroxysmal
      nocturnal hemoglobinuria (PNH), mannolipid products deriving from in vitro
      guanosine diphosphate [3H]Man labeling of HeLa cell microsomes were
      characterized. The defined GPI species were correlated with products deriving
      from in vivo [3H]Man labeling of normal and (GPI-anchor defective) affected
      leukocytes. In vitro analyses in HeLa cells showed dolichol-phosphoryl (Dol-P)
      [3H]Man and a spectrum of [3H]Man lipids exhibiting TLC mobilities approximating
      those of Trypanosoma brucei (Tryp) GPI precursors. Iatrobead HPLC separations and
      partial characterizations of the major isolated [3H]Man species (designated H1
      H8) showed that all but H1 (Dol-P-Man) were sensitive to HNO2 deamination and
      serum GPI-specific phospholipase D digestion but were resistant to
      phosphatidylinositol-specific phospholipase C digestion unless previously
      deacylated with mild alkali. [3H]Man label in H3, H4, and H6 but not in H5 or H7
      was efficiently released into the aqueous phase by jack bean alpha-mannosidase
      digestion. BioGel P-4 and AX-5 sizing of the dephosphorylated core glycan
      fragments of H6 and H7 gave values that coincided precisely with the
      corresponding glycan fragments from the fully assembled Tryp anchor donor A'
      (P2). Affected leukocytes from four patients with PNH supported formation of
      GlcNAc- and GlcN-PI but all failed to express H6 and H7 as well as H8 and two
      showed complete absence of earlier Man-containing intermediates. These findings
      argue that human intracellular GPI mannolipids are built on acylated inositol
      phospholipids, that H6 and H7 contain differentially phosphoethanolamine
      substituted Man3-GlcN-inositol cores, and that PNH cells are defective in
      conversion of GlcN-PI into these more mature mannolipid structures.

PMID- 1378629
TI  - An NK1.1+ CD4+8- single-positive thymocyte subpopulation that expresses a highly
      skewed T-cell antigen receptor V beta family.
AB  - In the present report we describe a CD4+8- heat stable antigen-negative (HSA-)
      thymocyte subpopulation that expresses a distinguishably low density of alpha
      beta T-cell antigen receptors (TCRlo) from the majority of CD4+8- high-density
      TCR (TCRhi) mature-type thymocytes. This subpopulation appears relatively late in
      life. Analysis of MEL-14, Pgp-1 (CD44), ICAM-1 (CD54), and NK1.1 expression on
      this subpopulation revealed that the CD4+8- TCRlo population was a population
      having unique characteristics (MEL-14-, CD44+, ICAM-1+, and NK1.1+) compared to
      the CD4+8- TCRhi thymocytes, most of which are MEL-14+, CD44-, ICAM-1-, and NK1.1
      . When TCR beta-chain variable region (V beta) usage was analyzed, this thymic
      population expressed predominantly products of V beta 7 and V beta 8.2 TCR gene
      families. Interestingly, cells with V beta 8.1 TCRs, which are reactive to Mls-1a
      antigens, were not eliminated from the CD4+8- HSA- TCRlo subpopulation but had
      been eliminated from the major CD4+8- HSA- TCRhi subpopulation in Mls-1a strains.
      A subset with a phenotype similar to the CD4+8- HSA- TCRlo thymocytes was also
      identified primarily in bone marrow, and this subset constituted approximately
      half of the CD4+ T cells in the bone marrow. The CD4+8- HSA- TCRlo cells showed
      extremely high proliferative responses to immobilized anti-TCR antibody but
      generated negligible responses to allogeneic H-2 antigens compared to the
      responses generated by the major CD4+8- HSA- CD3hi cells. However, the CD4+8- HSA
      TCRlo cells in Mls-1b mice mounted vigorous proliferative responses to Mls-1a
      antigens but not in Mls-1a mice. The properties of this T-cell subset suggest
      that these cells belong to a lineage distinct from the major T-cell population.

PMID- 1378627
TI  - CD5 is phosphorylated on tyrosine after stimulation of the T-cell antigen
      receptor complex.
AB  - When T cells are activated by the T-cell antigen receptor, a number of cellular
      proteins are phosphorylated on tyrosine. We investigated whether any of these
      proteins were present on the surface of activated T cells. Using the human
      leukemic T-cell line Jurkat and normal peripheral blood lymphocytes, we
      identified a 67-kDa cell surface glycoprotein in anti-phosphotyrosine
      immunoprecipitates, after treatment of the cells with CD3 antibody. When cell
      lysates were depleted of CD5 by sequential immunoprecipitation, the 67-kDa
      phosphotyrosyl polypeptide was no longer precipitated by the phosphotyrosine
      antibody. Western blot analysis of anti-phosphotyrosine precipitates confirmed
      that this glycoprotein was CD5. It was possible that CD5 was present in the anti
      phosphotyrosine immunoprecipitates due to its physical association with
      phosphotyrosyl proteins rather than being directly tyrosine-phosphorylated
      itself. However, Western blot analysis of anti-CD5 immunoprecipitates with
      phosphotyrosine antibody and phosphoamino acid analysis demonstrated that CD5 was
      indeed phosphorylated on tyrosine after stimulation of the cells with CD3
      antibody and was concomitantly phosphorylated on serine and threonine. Tyrosine
      phosphorylation of CD5 was maximal 2 min after CD3 stimulation and returned to
      baseline levels by 60 min. CD5 is expressed on the cell surface of all mature T
      cells and a small proportion of B lymphocytes and has recently been identified as
      the ligand for CD72, a receptor present on the surface of all B cells. The
      present data suggest that tyrosine phosphorylation may be involved in B-cell-T
      cell communication.

PMID- 1378625
TI  - Primary structure, expression, and signal-dependent tyrosine phosphorylation of a
      Drosophila homolog of extracellular signal-regulated kinase.
AB  - The extracellular signal-regulated kinases (ERKs) comprise a class of protein
      serine/threonine kinases that are activated in response to a wide variety of
      extracellular signals transduced via receptor tyrosine kinases. Activation of the
      ERKs requires both threonine and tyrosine phosphorylation suggestive of a key
      role in mediating intracellular events in response to extracellular cues. To
      critically assess the role of ERKs in intracellular signaling, a genetically
      tractable receptor tyrosine kinase system would be invaluable. In this paper we
      report the identification of a Drosophila homolog of ERK1 and -2, designated
      DmERK-A. DmERK-A is 80% identical to rat ERK1 and -2 and is rapidly
      phosphorylated on tyrosine in response to an extracellular signal activating a
      receptor tyrosine kinase. Biochemical and histological studies reveal its
      expression in the eye imaginal disc. These studies provide a first step in a
      genetic analysis of ERK function.

PMID- 1378634
TI  - Influences of cyclooxygenase inhibitors on the cataleptic behavior induced by
      haloperidol in mice.
AB  - Haloperidol administered intraperitoneally, and prostaglandin F2 alpha (PGF2
      alpha) and PGE2 intraventricularly induced dose-dependent cataleptic behavior in
      mice. The cataleptic behavior induced by haloperidol was inhibited dose
      dependently by oral pretreatment with aspirin and indomethacin, inhibitors of PGs
      synthetase. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole 3
      acetic acid (5-HIAA) were elevated by haloperidol, although dopamine (DA) and 5
      hydroxytryptamine (5-HT) levels did not change. The increase of DOPAC level in
      striatum induced by haloperidol was significantly suppressed by aspirin, but not
      in brain stem. The alteration of DOPAC level by aspirin correlated with the
      behavioral response. These results suggest that central prostaglandin synthesis
      may participate in the development of cataleptic behavior, which might also
      involve alteration of brain catecholaminergic activity.

PMID- 1378632
TI  - Competitive inhibition of nitric oxide synthase prevents the cortical hyperemia
      associated with peripheral nerve stimulation.
AB  - With combined microdialysis and hydrogen clearance techniques for simultaneous
      local delivery of drugs and blood-flow measurement in the rat hindlimb sensory
      motor cortex, we examined the role of nitric oxide in cerebral blood-flow
      regulation during sciatic nerve stimulation. Infusion of 1 mM nitric oxide
      synthase antagonist, N eta-nitro-L-arginine methyl ester (L-NAME), blocked the
      cortical blood-flow response to sciatic nerve stimulation (152 +/- 43 ml.min
      1.100 g-1 of tissue in controls and 73 +/- 11 ml.min-1.100 g-1 in the presence of
      L-NAME; P less than 0.05). Addition of 10 mM L-arginine to the dialysate
      containing L-NAME partially restored the hyperemic response to nerve stimulation
      (125 ml.min-1.100 g-1). L-NAME also produced a decrease in baseline cerebral
      blood flow when compared with the control (66 +/- 14 ml.min-1.100 g-1 vs. 93 +/-
      25 ml.min-1.100 g-1). We conclude that nitric oxide from activated neurons
      participates in the local regulation of cortical blood flow in response to
      sciatic nerve stimulation and also in the maintenance of basal cortical blood
      flow.

PMID- 1378630
TI  - Selective loss of a DNase I hypersensitive site upstream of the tyrosine
      aminotransferase gene in mice homozygous for lethal albino deletions.
AB  - Several overlapping chromosomal deletions spanning the albino locus in the mouse
      cause perinatal lethality when homozygous and a block in the transcriptional
      induction of various unlinked hepatocyte-specific genes. Studies of such lethal
      albino deletion homozygotes in perinatal stages revealed a deficiency in the
      transcriptional inducibility of the tyrosine aminotransferase (TAT) gene by
      glucocorticoids; yet, glucocorticoid receptor and hormone levels were shown to be
      unaffected. To identify a molecular defect underlying the failure of inducible
      expression, we examined the chromatin structure of the TAT gene. Whereas in wild
      type animals the TAT promoter becomes DNase I hypersensitive at birth, such
      hypersensitivity fails to develop in lethal albino deletion homozygotes. By
      contrast, the deletions do not affect the appearance of three DNase I
      hypersensitive sites upstream of the TAT promoter in the liver, nor do they
      affect two hypersensitive sites upstream of the expressed alpha-fetoprotein gene.
      These findings demonstrate that the abnormality of chromatin structure identified
      in lethal albino deletion homozygotes occurs on a highly selective basis.
      Specifically, normal differentiation of the TAT promoter chromatin appears to
      depend directly or indirectly on the action and product of a gene mapping within
      the deleted region.

PMID- 1378636
TI  - Wound chamber study of nerve and blood vessel growth.
AB  - Recent experimental studies using wound chambers (silicone tubes) sutured to the
      transected rat sciatic nerve or thigh muscle have shown an accumulation of plasma
      containing fluid and the formation of a fibrin/fibronectin clot within the
      chambers during the early phase. The plasma proteins leaked into the wound due to
      increased vascular permeability caused by the trauma. The fibrin/fibronectin clot
      in concert with neurotrophic factors play a key role in the promotion of growth
      and migration of endothelial cells, Schwann cells and axons during the early
      phase. Cessation of cell growth and migration coincided with removal of fibrin
      through fibrinolysis and collagen deposition in the extracellular space. The
      appearance of extracellular matrix was closely related to the morphological event
      of differentiation and formation of open capillaries and nerve fascicles. These
      findings suggest that in addition to hemostasis, fibrin polymerization
      (thrombosis) and fibrinolysis play vital pathophysiological roles in
      angiogenesis, nerve regeneration and other aspects of wound healing. These
      studies emphasize the importance of integrating information from many areas of
      research in order to understand some of the basic principles in Biology and
      Medicine.

PMID- 1378628
TI  - Directed establishment of rat brain cell lines with the phenotypic
      characteristics of type 1 astrocytes.
AB  - Interest in obtaining cell lines for use in studies on the development and
      biochemistry of the central nervous system has motivated efforts to establish
      cells from primary brain cultures by the use of oncogene-transfer techniques. In
      previous reports, cell lines derived from astrocytes in this way have had
      immature or abnormal phenotypes. We have explored the possibility of specifically
      "targeting" expression of exogenous oncogenes to differentiated astrocytes by
      using the promoter of the gene encoding glial fibrillary acidic protein, which is
      expressed almost exclusively in such cells. We report here that cell lines
      displaying the phenotypic characteristics of type 1 astrocytes can be established
      reproducibly in this manner. Given the heterogeneity of primary cultures, the
      availability of clonal cell lines displaying characteristics of type 1 astrocytes
      should greatly facilitate our understanding of the biology of these cells.

PMID- 1378633
TI  - Effect of haloperidol on cyclic AMP and inositol trisphosphate in rat striatum in
      vivo.
AB  - To investigate the effect of haloperidol (HAL) on second messengers in the brain
      striatum, the concentrations of cAMP and inositol trisphosphate (IP-3) were
      measured in the striatum of rats in vivo after intravenous administration of HAL,
      and their concentrations were compared with the severity of catalepsy and changes
      in dopamine (DA) metabolism in the striatum. Catalepsy developed both in the
      animals treated with 5 mg/kg and those with 0.5 mg/kg of HAL, but it appeared
      earlier, and the period of severe catalepsy was longer in the former than in the
      latter. In the animals treated with 5 mg/kg of HAL, DOPAC and HVA began to
      increase at 20 min after administration, and their percent increases were
      correlated with the severity of catalepsy. In the 5 mg/kg animals, both cAMP and
      IP-3 increased. The IP-3 showed a delayed peak but a greater increase as compared
      with the cAMP. In the 0.5 mg/kg animals, only IP-3 increased. These findings
      suggest that HAL might affect not only the adenylate cyclase system but also the
      phosphoinositide response in the striatum. Moreover, the changes in the
      phosphoinositide response might be secondarily induced by the blocking of D-2
      receptors by HAL.

PMID- 1378635
TI  - Long-term neurochemical and behavioral effects induced by acute chlorpyrifos
      treatment.
AB  - A single dose of the organophosphate insecticide O,O'-diethyl-O-3,5,6- trichloro
      2-pyridylphosphorothioate [chlorpyrifos (CPF), 279 mg/kg, SC] caused extensive
      inhibition of cortical and striatal cholinesterase (ChE) activity in adult rats
      at 2 (94-96%), 4 (82-83%), and 6 (58-60%) weeks after treatment. These persistent
      changes in ChE activity were concomitant with reductions in muscarinic receptor
      binding sites in cortex (34, 33, and 18% reduction in Bmax) and striatum (48, 40,
      and 23% reduction in Bmax) at 2, 4, and 6 weeks after exposure. Neither ChE
      activities nor muscarinic receptor densities were different from control levels
      at 12 weeks after exposure. CPF treatment caused a reduction in locomotor
      activity for the first 2 days after treatment, after which basal activity levels
      were not different from controls. CPF-treated rats showed higher activity
      relative to controls, however, following challenge with scopolamine (1 mg/kg, IP)
      at 2, 4, 6, 8, and 12 weeks after treatment. These data indicate that acute
      exposure to CPF in adult rats can cause long-term neurobehavioral changes that
      may persist following the recovery of neurochemical parameters associated with
      exposure and tolerance to cholinesterase inhibitors.

PMID- 1378631
TI  - A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal
      for cognate activation of B cells.
AB  - CD40 is a B-cell surface molecule that has been shown to induce B-cell growth
      upon ligation with monoclonal antibodies. This report shows that triggering via
      CD40 is essential for the activation of resting B cells by helper T cells (Th). A
      soluble fusion protein of CD40 and human immunoglobulin, CD40-Ig, inhibited the
      induction of B-cell cycle entry, proliferation, and differentiation by activated
      Th1 and Th2. The ligand for CD40 was identified as a 39-kDa membrane protein that
      was selectively expressed on activated Th. A monoclonal antibody specific for the
      39-kDa protein inhibited CD40-Ig binding and also inhibited the activation of B
      cells by Th. These data indicate that the 39-kDa membrane protein expressed on
      activated Th is a binding protein for CD40 and functions to transduce the signal
      for Th-dependent B-cell activation.

PMID- 1378637
TI  - The physiology of GABAA receptors in retinal neurons.

PMID- 1378638
TI  - The physiology of GABAB receptors in the vertebrate retina.
AB  - Writing a chapter on retinal GABAB receptors is premature, as evidenced by the
      paucity of citations more than two years old. Despite that, this area of retinal
      pharmacology has made significant strides and, although it is a story without an
      ending, it has had an exciting beginning. To date, the experiments indicate that
      horizontal cell feedback to cones is mediated, at least in part, by the GABAB
      receptor system which probably regulates a potassium conductance. In the inner
      retina, GABAB receptors are found on bipolar cells, amacrines, and ganglion
      cells. Here, the actions are a subtle regulation of channel conductance, but the
      effects are a dramatic reorganization of a fundamental coding property of the
      retina, namely the distinction between tonic and phasic responses to light. In
      both the distal and proximal retina, the GABAB receptor does not appear to work
      alone, but instead works in concert with the GABAA receptor. The full
      significance of these interactions has yet to be determined. Although the
      discovery of the GABAB receptor has led to the resolution of several retinal
      mysteries, the case is far from closed. At this juncture, what can be said is
      that the GABAB receptor represents a unique and ubiquitous system that reveals
      the power of regulating calcium and potassium conductances, as opposed to the
      more familiar properties of the glutamate/acetylcholine regulated cationic
      conductances or the GABAA/glycine controlled chloride channels.

PMID- 1378639
TI  - Dexamethasone inhibition of cyclooxygenase expression in bovine term placenta.
AB  - Since both prostaglandin (PG) F2 alpha and corticosteroids are elevated in
      mammals before the onset of parturition, we studied the effect of the synthetic
      corticosteroid dexamethasone on PGF2 alpha accumulation and cyclooxygenase
      (prostaglandin synthase, PGS) expression in the bovine fetal placenta. Cultures
      were prepared from cotyledons at different stages of gestation. The effect of
      dexamethasone on PGF2 alpha accumulation and PGS expression was determined by
      radioimmunoassay and [35S]methionine metabolic labeling followed by
      immunoprecipitation with specific anti-cyclooxygenase antibodies, respectively.
      Data demonstrate that in fetal placental cells at term, both PGF2 alpha
      accumulation and cyclooxygenase expression are significantly inhibited after 18
      hours of dexamethasone treatment (150 nM). In contrast, neither first nor second
      trimester cells were sensitive to dexamethasone treatment. Dexamethasone
      inhibition of PGF2 alpha synthesis in fetal cells at term was abolished in the
      presence of RNA or protein synthesis inhibitors (actinomycin D or puromycin, 10
      micrograms/ml each). Neither progesterone nor 17 beta-estradiol accumulation were
      affected by dexamethasone treatment at any stage of gestation. Data suggest that
      corticosteroids play a role in parturition through PGF2 alpha synthesis
      regulation by fetal placental cells. Since abnormalities during parturition e.g.
      retained placenta, are common following dexamethasone induction of labor in cows,
      we postulate that the local inhibition of PGF2 alpha accumulation by cotyledon
      cells after corticosteroid administration, may be involved in placental
      retention.

PMID- 1378640
TI  - Comparison of Iloprost, Cicaprost and prostacyclin effects on cyclic AMP
      metabolism in intact platelets.
AB  - We have compared the effects of prostacyclin (PGI2) and its stable analogs,
      Iloprost and Cicaprost, on cyclic AMP metabolism in intact platelets. All three
      compounds show similar but not identical patterns of prostaglandin concentration
      dependent cyclic AMP formation. All three compounds apparently stimulate and
      inhibit cyclic AMP formation with different concentration dependencies,
      indicating the presence of distinct stimulatory and inhibitory receptors.
      Differences in response can be accounted for by slight differences in affinity of
      stimulatory and inhibitory receptors for the prostaglandins, by the fact that
      Iloprost contains almost 50% of a relatively inactive isomer, and by the fact
      that PGI2 is labile in aqueous solution, with a half-life on the order of a few
      minutes. We conclude 1) stimulation and inhibition of adenylate cyclase is not
      due to separate effects of 16S- and 16R-stereoisomers of Iloprost because similar
      patterns were obtained with a single isomeric form of Cicaprost and with
      authentic PGI2; 2) prostaglandin induced inhibition of adenylate cyclase is
      readily reversible because inhibition disappears when PGI2 concentration decays
      below saturation of the inhibitory receptor; 3) the potency of prostaglandins in
      stimulating platelet adenylate cyclase must be viewed in terms of their effects
      on both stimulatory and inhibitory receptors.

PMID- 1378641
TI  - [Chemo-radiotherapy in advanced head and neck tumors. Personal experience].
AB  - From January 1981 through December 1983, 49 untreated patients with locally
      advanced head and neck cancers were randomized in two groups to receive different
      radiochemotherapy regimens. Group A, including 29 cases, received 4 cycles of
      induction chemotherapy with Bleomycin, Methotrexate and Hydroxyurea before
      definitive external radiotherapy (60 Gy); group B, including 20 patients,
      received the same total dose of radiotherapy but the 4 cycles of chemotherapy, as
      described above, were administered between the 20- and the 40-Gy doses. Both
      groups were compared with a control group treated in the same period with
      radiotherapy (60 Gy) alone. The response to treatment was evaluated at the end of
      chemotherapy or radiotherapy alone and at the end of combined regimens. Long-term
      survival rates were analyzed for all groups relative to complete tumor response,
      disease-free interval and time to disease progression. In our experience the
      radio-chemotherapy combination, according to the described schedules, failed to
      improve both local control and overall survival; the comparison with the control
      group does not suggest that induction or intercalated chemotherapy can increase
      long-term survival even if initial complete and partial response rates are high.

PMID- 1378642
TI  - [Indications for bone marrow graft in severe hemoglobinopathies].
AB  - Allogenic bone marrow transplantation (ABMT) is the only curative approach for
      sickle cell anemia and major beta-thalassemia. In sickle cell anemia, ABMT can be
      proposed for severe clinical disease. In major beta-thalassemia, it must be
      proposed to young patients who have an HLA identical familial donor.

PMID- 1378643
TI  - [Bile duct endoprostheses in tumor disease: when is the expense justified?].
AB  - Percutaneous transhepatic catheters should be reserved for the minority of
      palliatively treated tumor patients because of the chronic complications and the
      discomfort to the patients. Plastic biliary endoprostheses relief malignant
      obstructive jaundice in most patients sufficiently. Late complications such as
      occlusion and displacement occur relatively often. The major advantages of
      expandable metal stents are the relative ease and the low rate of complications
      during the insertion procedure. The wide lumen and the small surface ensure good
      flow of bile and reduce the risk of occlusion and cholangitis. However, further
      development is necessary and the very expensive devices should be restricted to
      those patients with long life expectancy.

PMID- 1378644
TI  - [Screening for hepato-cellular carcinoma].

PMID- 1378645
TI  - [Early case-finding of hepatocarcinoma].

PMID- 1378646
TI  - [Female contraception by a normal dose progestogen after 40 years of age.
      Possible association of nomegestrol--17-beta-estradiol acetate by percutaneous
      route].
AB  - Although fertility declines with age, the use of an effective contraceptive
      remains necessary in women over 40. Endocrine disorders, which are common in this
      age group, may also often require control. Conventional estroprogestogens, even
      those of the latest generation, cannot be used in women with a high
      cardiovascular risk, since age cannot be totally excluded as a possible risk
      factor. The contraceptive use of derivatives of 17-hydroxyprogesterone and 19
      norprogesterone offer a promising alternative, despite the absence of any
      exhaustive investigation particularly in situations in which the blood level of
      estradiol has to be reduced. There are, however, some women who respond to this
      type of contraception by menstrual cycle irregularities, and sometimes by low
      blood levels of estradiol, regardless of the drug used. A preliminary study is
      described in which 5 mg of nomegestrol acetate was combined with 17-beta
      estradiol by transcutaneous route and which has so-far demonstrated sustained
      contraceptive efficacy as well as excellent clinical and metabolic safety.

PMID- 1378647
TI  - Effect of ultrasound guided core biopsy of prostate on serum concentration of
      prostate specific antigen and acid phosphatase activity.
AB  - Forty-three patients had their serum concentrations of prostate specific antigen
      and activity of tartrate inhibited acid phosphatase measured before and after
      digital rectal examination, transrectal ultrasonography and transrectal core
      biopsy. Transrectal core biopsy significantly increased the values for both tumor
      markers but rectal examination and ultrasonography without biopsy had no such
      effect. The measurements returned to normal within one week of biopsy in all but
      four patients who still had slightly increased concentrations of prostate
      specific antigen. We recommend that the concentration of prostate specific
      antigen and activity of tartrate inhibited acid phosphatase are checked before
      biopsy of the prostate is carried on.

PMID- 1378648
TI  - Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase
      II mutant mice.
AB  - As a first step in a program to use genetically altered mice in the study of
      memory mechanisms, mutant mice were produced that do not express the alpha
      calcium-calmodulin-dependent kinase II (alpha-CaMKII). The alpha-CaMKII is highly
      enriched in postsynaptic densities of hippocampus and neocortex and may be
      involved in the regulation of long-term potentiation (LTP). Such mutant mice
      exhibited mostly normal behaviors and presented no obvious neuroanatomical
      defects. Whole cell recordings reveal that postsynaptic mechanisms, including N
      methyl-D-aspartate (NMDA) receptor function, are intact. Despite normal
      postsynaptic mechanisms, these mice are deficient in their ability to produce LTP
      and are therefore a suitable model for studying the relation between LTP and
      learning processes.

PMID- 1378649
TI  - Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas.
AB  - Immature T cells and some T cell hybridomas undergo apoptotic cell death when
      activated through the T cell receptor complex, a phenomenon that is probably
      related to antigen induced negative selection of developing T cells. This
      activation-induced apoptosis depends on active protein and RNA synthesis in the
      dying cells, although none of the genes required for this process have previously
      been identified. Antisense oligonucleotides corresponding to c-myc block the
      constitutive expression of c-Myc protein in T cell hybridomas and interfere with
      all aspects of activation-induced apoptosis without affecting lymphokine
      production in these cells. These data indicate that c-myc expression is a
      necessary component of activation-induced apoptosis.

PMID- 1378650
TI  - Nitric oxide: a physiologic mediator of penile erection.
AB  - Nitric oxide (NO) is a cytotoxic agent of macrophages, a messenger molecule of
      neurons, and a vasodilator produced by endothelial cells. NO synthase, the
      synthetic enzyme for NO, was localized to rat penile neurons innervating the
      corpora cavernosa and to neuronal plexuses in the adventitial layer of penile
      arteries. Small doses of NO synthase inhibitors abolished electrophysiologically
      induced penile erections. These results establish NO as a physiologic mediator of
      erectile function.

PMID- 1378651
TI  - Six new cases of a caterpillar-induced bleeding syndrome.
AB  - We describe six new cases of a hemorrhagic diathesis induced by contact with
      Lonomia achelous caterpillars. Onset of clinical bleeding varied between a few
      hours and 10 days post-exposure. Laboratory coagulation tests showed prolonged
      PT, PTT and ThT; normal platelets and a marked decrease of fibrinogen, factor V,
      plasminogen and factor XIII (including its subunits A and S). Factors VII, II and
      alfa 2 anti-plasmin were variably affected. In addition, activation of the
      fibrinolytic system and the generation of a procoagulant effect could also be
      demonstrated. Two cases developed severe hemorrhagic diathesis and one of them
      died of a cerebral hemorrhage. Different aspects of this rare syndrome are
      discussed in relation to its complex physiopathology and the variability observed
      in all clinical and laboratory manifestations. Therapeutic recommendations and
      some possible hazards following replacement transfusions are also considered.

PMID- 1378652
TI  - Human vascular endothelial cells catabolise exogenous glycosaminoglycans by a
      novel route.
AB  - Heparin and other anticoagulant glycosaminoglycans were radiolabelled with 125I
      and their catabolism by human vascular endothelial cells in culture was studied.
      Heparin, heparan sulphate and pentosan polysulphate were associated with the
      cellular fraction and incorporated into the subendothelial matrix, but dermatan
      sulphate was not found in either fraction. High molecular weight, fully
      desulphated carbohydrate chains were major catabolic products of all those
      glycosaminoglycans which were taken up by the cells. Pentosan polysulphate was
      not degraded further, but the catabolism of heparan sulphate, and to a lesser
      extent that of heparin, also yielded small oligosaccharides. Thus the first step
      in catabolism of exogenous glycosaminoglycans by human vascular endothelial cells
      appears to be complete desulphation, which destroys their biological activity,
      followed by depolymerisation of the carbohydrate chain. This alternative to the
      sequential action of lysosomal exoenzymes is dependent upon binding to the cell;
      thus dermatan sulphate, which is not associated with the cellular fraction, is
      not catabolised.

PMID- 1378653
TI  - Characterization of a factor VIII immunogenic site using factor VIII synthetic
      peptide 1687-1695 and rabbit anti-peptide antibodies.
AB  - A 9 amino acid peptide, Ser-Pro-Arg-Ser-Phe-Gln-Lys-Lys-Thr, corresponding to the
      clotting factor VIII (FVIII) sequence Ser1687-Thr1695, was synthesized in order
      to analyze a site on FVIII to which antibody inhibitors of FVIII may be directed.
      This sequence contained a thrombin cleavage site. It was predicted to be
      immunogenic because a Hopp-Woods hydrophilicity analysis of the amino acid
      sequence of FVIII showed it to be very hydrophilic, and it contained a proline.
      The HPLC-purified peptide was cleaved by thrombin at Arg1689-Ser1690, as
      determined by amino acid sequencing of the cleavage product. Thrombin which had
      been treated with a specific chloromethyl ketone inhibitor, did not cleave the
      peptide. Two rabbits immunized with the peptide/keyhole limpet hemocyanin
      conjugate generated FVIII inhibitory sera with titers of 5.4 and 4.8 Bethesda
      units. These rabbit anti-peptide antibodies reacted with a peptide/-BSA conjugate
      on immunodot blot analyses and with native, affinity-purified FVIII in Western
      blots. In competitive immunoradiometric assays, cryosupernatants of 38/82
      patients with FVIII inhibitors reacted with the synthetic peptide. We conclude
      that FVIII peptide Ser1687-Thr1695 is cleaved by thrombin at the same peptide
      bond which is cleaved in FVIII, and the peptide contains a site to which
      patients' inhibitory antibodies can be directed.

PMID- 1378654
TI  - [Is morphine a substitute for radiotherapy?].

PMID- 1378655
TI  - [Is cancer pain therapy insufficient?].
AB  - Pain from cancer is said to be poorly relieved. To examine the relevance of this
      statement in our hospital we registered morphine consumption used for cancer pain
      relief from 1983 to 1990. The use of morphine increased 20-fold during this
      period, corresponding to a 12-fold increase per patient. A probable explanation
      of this development is that cancer pain now receives more attention and use of
      morphine has become more acceptable. New methods such as subcutaneous continuous
      morphine administration from portable pumps, and the introduction of slow-release
      morphine, have improved and simplified the treatment. Probably several Norwegian
      hospitals still lag behind in this respect. Consequently much pain remains
      unrelieved. We suggest that hospitals evaluate their pain relief programmes. If
      these are found inadequate, the service should be reinforced. This would probably
      lead to earlier rehabilitation and improved quality of life for the patient.

PMID- 1378656
TI  - [Morphine-antiemetics mixtures for continuous subcutaneous infusion in terminal
      cancer].
AB  - Simultaneous pain, nausea and vomiting are not uncommon in terminal suffering
      requiring treatment with various compounds of analgesics and antiemetics. At
      Baerum Hospital the pump reservoirs for continuous, subcutaneous drug delivery
      are routinely filled by the hospital pharmacist. We examined the physico-chemical
      stability of various concentrations of mixtures of morphine-metoclopramide and
      morphine-metoclopramide-haloperidol at 25 degrees C. We found good stability for
      at least seven days. Addition of haloperidol seems to reduce stability. Plain
      morphine-haloperidol solutions are unstable. Split products were not found in any
      of the mixtures. We also examined the osmolality of current clinical compounds,
      focusing on local irritant effect at the infusion site. All solutions except for
      one with a high concentration of haloperidol were found to be close to
      isoosmolarl.

PMID- 1378657
TI  - [Continuous drug infusion in terminal cancer].
AB  - Today's technology provides portable pumps which facilitate continuous infusion
      of drugs to relieve suffering in terminal disease. Subcutaneous and epidural
      infusion is now frequently used in our hospital. The most common indications are
      gastrointestinal obstruction, impaired absorption of drugs, refractory side
      effects of oral medication or poor compliance because good pain relief is no
      longer possible orally. During the last days of life, this method may be the only
      possible approach to good comfort and relief from terminal agitation and anxiety.
      Of the patients referred to the advisory group for seriously ill and dying in
      1990, 64% received subcutaneous infusions and 15% epidural infusions during the
      last days or weeks of life. Continuous infusion of drugs from portable pumps has
      become an almost indispensible method of treatment in an ordinary clinic.

PMID- 1378658
TI  - In vivo assessment of neovascularization and incorporation of prosthetic vascular
      biografts.
AB  - Neovascularization plays a major role in prosthetic vascular graft healing. New
      developments in manufacturing biomaterials have encouraged the use of biological
      and biosynthetic materials for both arterial replacement and bypass procedures.
      We have analyzed in vivo the process of neovascularization and incorporation of
      biolized bovine carotid artery (Solco P), a biological material, and the
      composite of ovine collagen and polyester mesh (Omniflow), a biosynthetic
      material. The synthetic fabric polytetrafluorethylene (e-PTFE), which is widely
      used in cardiovascular surgery, served as control. Using the dorsal skinfold
      chamber of the Syrian golden hamster as site for implantation (n = 15),
      angiogenesis and neovascularization were analyzed quantitatively by means of
      intravital fluorescence microscopy. In each chamber a piece (approximately 1 mm2)
      of each of the three vascular grafts was implanted. Five days after implantation
      neovascularization was ascertained in 90% of the Omniflow grafts, while only 40%
      of the PTFE and 20% of the Solco P implants revealed new ingrowing microvessels.
      On day 10 the density of newly formed microvessels was significantly higher (p
      less than 0.01) in Omniflow grafts (263.5 +/- 24.1 cm-1) as compared to PTFE
      (134.2 +/- 20.8 cm-1) and Solco P (153.2 +/- 32.0 cm-1). In addition, the
      biosynthetic composite revealed a larger extension of neovascularization into the
      perigraft tissue, and 12 days after implantation these grafts were most tightly
      incorporated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378659
TI  - Inhibition of mitochondrial Ca2+ release diminishes the effectiveness of methyl
      mercury to release acetylcholine from synaptosomes.
AB  - The interaction of methyl mercury (MeHg) with nerve-terminal mitochondria as a
      potential mechanism for its effects on the release of acetylcholine (ACh) was
      studied using rat brain synaptosomes. The primary goal was to assess the relative
      contribution of extracellular Ca2+ and Ca2+ released from nerve-terminal
      mitochondria to the previously described stimulatory effects of MeHg on
      spontaneous release of ACh. A secondary goal was to address possible mechanisms
      by which MeHg might interact with nerve-terminal mitochondria to elicit Ca2+
      discharge and subsequent release of ACh. MeHg depressed the high-affinity uptake
      of [3H]choline into synaptosomes by approximately 25 and 45% when synaptosomes
      were incubated with [3H]choline in the presence of 10 and 100 microM MeHg,
      respectively. In Ca(2+)-containing solutions, 10 and 100 microM MeHg increased
      the release of [3H]ACh from [3H]choline-loaded synaptosomes by 10 and 30%,
      respectively; this effect was maximal at 10 sec. Excluding Ca2+ from the reaction
      medium diminished the effectiveness of both 10 and 100 microM MeHg for inducing
      [3H]ACh release by about 30 and 25%, respectively, from that of Ca(2+)-containing
      solutions; however, significant increases still occurred in nominally Ca(2+)-free
      solutions. Ruthenium red (RR), an inhibitor of mitochondrial Ca2+ transport, was
      tested for its ability to disrupt MeHg-induced release. RR alone increased
      [3H]ACh release by 8-10 and 10-13% at 20 and 60 microM, respectively. RR-induced
      release was attenuated only slightly in Ca(2+)-free solutions. Preincubation of
      [3H]choline-loaded synaptosomes with RR reduced the stimulatory effect of MeHg on
      release of [3H]ACh both in the presence and in the absence of Ca2+. The
      fluorescent potentiometric carbocyanine dye diS-C2(5) was used to assess the
      ability of RR to prevent MeHg-induced depolarization of intrasynaptosomal
      mitochondria. RR (20 microM) itself did not depolarize the mitochondrial membrane
      potential, nor did it prevent MeHg from depolarizing the mitochondria. The
      results indicate that extracellular Ca2+ contributes only partially to MeHg
      induced spontaneous release of ACh. The results with RR suggest that MeHg
      interacts with mitochondria to induce release of bound intraterminal Ca2+ stores,
      resulting ultimately in stimulated release of ACh. The ability of RR to prevent
      release of mitochondrial Ca2+ and, subsequently, ACh is not due to prevention of
      access of MeHg to the mitochondria, nor to stabilization of the mitochondrial
      membrane. Finally, MeHg reduces choline uptake into nerve terminals. Thus, MeHg
      could interfere with cholinergic neurotransmission by affecting the regulatory
      step in ACh synthesis and by increasing the spontaneous release of
      transmitter.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1378660
TI  - 'Cartellian' competition at the neuromuscular junction.

PMID- 1378661
TI  - An 'anatomical cascade hypothesis' for Alzheimer's disease.
AB  - The molecular mechanisms of the cytopathology of Alzheimer's disease are very
      rapidly being elucidated. However, the factors that restrict the effects of this
      disease to specific neuroanatomical systems are less well understood. In this
      brief article a possible hypothesis is outlined to explain this apparent specific
      localization.

PMID- 1378662
TI  - Dopamine receptor interactions: some implications for the treatment of
      Parkinson's disease.
AB  - Since the discovery that L-DOPA could alleviate the symptoms of Parkinson's
      disease, it has been assumed that the striatum is the site of action of the
      dopamine formed from L-DOPA. However, for the past 15 years, evidence has
      accumulated to suggest that dopamine is also released by the dendrites of
      dopamine neurons in the substantia nigra and D1 dopamine receptors in this region
      of the brain appear to play an important role in the actions of L-DOPA.
      Activation of D1 receptors in the substantia nigra may, in part, explain some of
      the synergistic effects of D1 and D2 agonists in animal models for Parkinson's
      disease. These effects are discussed in light of recent studies suggesting that
      dopamine, acting on D1 and D2 dopamine receptor subtypes, activates distinct
      efferent pathways from the striatum. Clinical studies suggest that these findings
      may have important implications for the treatment of Parkinson's disease.

PMID- 1378664
TI  - How inaccurate is the Abercrombie correction factor for cell counts?

PMID- 1378663
TI  - How complex is the nicotinic receptor system of insects?
AB  - In insects, nicotinic acetylcholine receptors (nAChRs) are confined to the
      nervous system. It is a long-standing open question whether the insect nicotinic
      cholinergic receptor system is less complex than that of the vertebrate nervous
      system. Simplicity can be conceived in two ways. (1) Fewer receptor subtypes may
      exist. (2) Single receptors may have a more primitive (homo-oligomeric)
      quaternary structure. Recent approaches to the molecular cloning of insect nAChRs
      may contribute valuable new information to this issue. Thus, the identification
      of multiple genes encoding proteins similar to vertebrate nAChR subunits
      implicates a remarkable heterogeneity for these receptors. The discovery of
      putatively non-ligand-binding subunits hints to the existence of vertebrate-like
      hetero-oligomeric nAChRs. However, the simultaneous occurrence of homo-oligomeric
      receptors must still be considered.

PMID- 1378665
TI  - Eye regionalization and spectral tuning of retinal pigments in insects.
AB  - The spatial and spectral properties of an eye can often be directly linked to the
      behaviour and habitat of the animal. In a honey bee (Apis mellifera) society, the
      drones use the well-developed dorsal part of the eye to detect the queen against
      the sky during her nuptial flight. Recently it has become clear that the dorsal
      area of the drone's eye serves its task by cleverly combining a number of optical
      mechanisms, thus achieving a high spatial acuity as well as a high sensitivity
      precisely in the wavelength range of interest--the ultraviolet to blue range.
      Since the various optical specializations in the drone eye have now been
      recognized, they can be traced in the eyes of other species: thus, the drone eye
      serves as a model to give a better understanding of the relationship between
      structure and function of compound eyes in particular, but also of visual systems
      in general.

PMID- 1378666
TI  - Temporal coding in the visual cortex: new vistas on integration in the nervous
      system.
AB  - Although our knowledge of the cellular components of the cortex is accumulating
      rapidly, we are still largely ignorant about how distributed neuronal activity
      can be integrated to contribute to unified perception and behaviour. In the
      visual system, it is still unresolved how responses of feature-detecting neurons
      can be bound into representations of perceptual objects. Recent crosscorrelation
      studies show that visual cortical neurons synchronize their responses depending
      on how coherent features are in the visual field. These results support the
      hypothesis that temporal correlation of neuronal discharges may serve to bind
      distributed neuronal activity into unique representations. Furthermore, these
      studies indicate that neuronal responses with an oscillatory temporal structure
      may be particularly advantageous as carrier signals for such a temporal coding
      mechanism. Based on these recent findings, it is suggested here that binding of
      neuronal activity by a temporal code may provide a solution to the problem of
      integration in distributed neuronal networks.

PMID- 1378667
TI  - Local circuits for the control of leg movements in an insect.
AB  - To produce behaviour that is adaptive, local circuits in the CNS must transform
      mechanosensory signals from receptors on the body into changes in movement.
      Substantial insights into the mechanisms underlying these transformations can be
      obtained by analysing the local circuits of animals from which intracellular
      recordings can be made from identified neurones during behavior, thus allowing
      the complete pathways between inputs and outputs to be followed. In the locust
      (Schistocerca gregaria) these circuits contain both non-spiking and spiking local
      neurones so that it is possible to elucidate two basic issues of neuronal
      integration: (1) the operation of the reflex circuitry that must adjust
      locomotion, and (2) the integrative role of local circuits that use graded
      interactions in complex neuropil, perhaps even involving compartmentalized
      neurones.

PMID- 1378668
TI  - [Hematopoietic growth factors in primary and therapy-related bone marrow
      insufficiency].
AB  - This investigation is retrospective and comprises 20 patients with bone-marrow
      insufficiency. During the period 1.4.1988-1.3.1991, these patients were treated
      with erythropoietin (Epo), the granulocyte-macrophage-colony-stimulating factor
      (GM-CSF) or the granulocyte-colony-stimulating factor (G-CSF). Thirteen patients
      had primary bone-marrow insufficiency: six had the myelodysplastic syndrome,
      three had primary myelofibrosis, two aplastic anemia and two myelomatosis. On
      account of dominating symptoms of anemia, five patients received Epo while eight
      received GM-CSF as part of an extensive clinical trial of this preparation. Seven
      patients with relapse of the haematological malignant disease had bone-marrow
      insufficiency and pancytopenia secondary to intensive chemotherapy/irradiation:
      four of these patients received GM-CSF and two received G-CSF with the object of
      increasing bone-marrow regeneration and to render further chemotherapy possible.
      One patient received GM-CSF with the object of improving bone-marrow function
      after autologous bone-marrow transplantation. Treatment with Epo for ten months
      combined with treatment with interferon for six months resulted in normalization
      of the haemoglobin concentration in one patient with bone-marrow insufficiency on
      account of primary myelofibrosis. Treatment with Epo for briefer periods in lower
      doses was without effect in four other patients with primary bone-marrow
      insufficiency. Treatment with GM-CSF and G-CSF resulted in neutrophil
      leukocytosis in 12 out of 15 patients (80%) and, in six out of 14 patients (43%),
      increased marrow cellularity was demonstrated by means of histological
      examination of the bone-marrow. One patient showed normal haemoglobin levels
      during treatment with GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378669
TI  - Pulmonary inflammation associated with aspirated meconium and epithelial cells in
      calves.
AB  - "Meconium aspiration syndrome" is a condition resulting in respiratory distress
      and the occasional death of newborn human beings. A retrospective study was
      conducted on 52 calves that were submitted for postmortem examination to the
      Atlantic Veterinary College, Charlottetown, Prince Edward Island, Canada. These
      calves died of infectious and noninfectious diseases within the first 2 weeks of
      life due to a variety of causes. The most common cause of death was infectious
      enteric disease. Histologic examination of lungs revealed that 42.5% of calves
      had evidence of meconium, squamous cells, or keratin in the lung. There was
      considerable variation in the magnitude of histologic changes in lungs containing
      aspirated material. Typically, affected lungs had only a few inconspicuous pieces
      of meconium, keratin, and squamous cells within bronchoalveolar spaces.
      Sporadically, the entire lumen of airways was obliterated by aspirated material.
      Lungs with aspirated material had a mild but diffuse alveolitis characterized by
      exudation of a few neutrophils, macrophages, and occasional multinucleated giant
      cells. Obstruction of small airways and focal atelectasis were also observed.
      Similar lesions have been reported in human meconium aspiration syndrome. It is
      concluded that histologic changes similar to those of human meconium aspiration
      syndrome occur commonly in calves that die within 2 weeks of birth. Further
      studies involving healthy age-matched calves are required to evaluate the
      clinicopathologic significance of meconium aspiration in this species.

PMID- 1378670
TI  - Genetic susceptibility of indigenous chicks to subgroup A Rous sarcoma virus
      inoculated via the chorioallantoic membrane.
AB  - An investigation was made using chicks of two Indian indigenous breeds of fowl,
      Kadaknath and Aseel, to ascertain genetic resistance to infection by Rous sarcoma
      virus of subgroup A. A standard inoculation dose of 0.2 ml virus containing 1000
      pock forming units ml-1 was injected via the chorioallantoic membrane (CAM) into
      the 11-day-old embryos that were subsequently hatched. The sensitivity of the two
      indigenous breeds was compared with the highly susceptible exotic White Leghorn
      (WL) strain maintained in the laboratory. The Kadaknath breed was about three
      fold and Assel, about six-fold less sensitive than the WL strain, indicating
      superiority of the indigenous breeds over the exotic breed of fowl. Most of the
      CAM-susceptible chicks died of liver tumour (LT) and most of the CAM-resistant
      chicks survived. However, conversely associated tumour phenotype subclass chicks,
      i.e. CAM-susceptible LT-negative chicks that survived and CAM-resistant LT
      positive chicks that died, occurred consistently in the three breeds of fowl.
      Nevertheless, the overall survival potential of Kadaknath chicks measured up to 8
      weeks post-hatching was greater than that of Aseel chicks. Neither transformation
      of embryonic tissue prior to hatching nor the visceral metastasis including liver
      conformed with the degree of CAM-infection as measured by number of pocks on
      CAMs.

PMID- 1378671
TI  - National Hospital Discharge Survey.
AB  - This report presents statistics on the utilization of non-Federal short-stay
      hospitals based on data collected through the National Hospital Discharge Survey
      from a national sample of hospital records of discharged inpatients. Estimates
      are provided by the demographic characteristics of patients discharged,
      geographic region of hospitals, conditions diagnosed, and surgical and
      nonsurgical procedures performed. Measurements of hospital use include frequency,
      rate, percent of discharges and days of care, and average length of stay.

PMID- 1378672
TI  - Antioxidant and pro-oxidant properties of active rosemary constituents: carnosol
      and carnosic acid.
AB  - 1. Carnosol and carnosic acid have been suggested to account for over 90% of the
      antioxidant properties of rosemary extract. 2. Purified carnosol and carnosic
      acid are powerful inhibitors of lipid peroxidation in microsomal and liposomal
      systems, more effective than propyl gallate. 3. Carnosol and carnosic acid are
      good scavengers of peroxyl radicals (CCl3O2.) generated by pulse radiolysis, with
      calculated rate constants of 1-3 x 10(6) M-1 s-1 and 2.7 x 10(7) M-1 s-1
      respectively. 4. Carnosic acid reacted with HOCl in such a way as to protect the
      protein alpha 1-antiproteinase against inactivation. 5. Both carnosol and
      carnosic acid stimulated DNA damage in the bleomycin assay but they scavenged
      hydroxyl radicals in the deoxyribose assay. The calculated rate constants for
      reaction with .OH in the deoxyribose system for carnosol and carnosic acid were
      8.7 x 10(10) M-1 s-1 and 5.9 x 10(10) M-1 s-1 respectively. 6. Carnosic acid
      appears to scavenge H2O2, but it could also act as a substrate for the peroxidase
      system. 7. Carnosic acid and carnosol reduce cytochrome c but with a rate
      constant significantly lower than that of O2(-.).

PMID- 1378673
TI  - [Clinical importance of organ-specific antibodies in ulcerative colitis and Crohn
      disease].
AB  - In 479 patients with chronic inflammatory intestinal diseases and other abdominal
      diseases autoantibodies against intestinal goblet cells and exocrine pancreas
      were determined by indirect immunofluorescence. In ulcerative colitis 17% had
      serum antibodies against intestinal goblet cells, in Crohn's disease 26% against
      exocrine pancreas. Autoantibody prevalence and level of the titre were dependent
      on the inflammatory activity of both diseases but independent on the therapy. In
      Crohn's disease high level of titres of antibodies against exocrine pancreas we
      found in cases with multiple complications. Antibodies titres against intestinal
      goblet cells in ulcerative colitis and against exocrine pancreas in Crohn's
      disease exceeding 1:100 improved the diagnostic decision. Besides clinical
      states, endoscopic and histological findings a positive result of the antibody
      investigations had to be considered for final diagnosis.

PMID- 1378674
TI  - Clinical and electrophysiologic studies of R61748 (transcainide): a new class Ic
      antiarrhythmic drug.
AB  - The electrophysiology and antiarrhythmic efficacy of R61748, a 4-OH metabolite of
      R54718 (transcainide), have been studied in patients and animal experiments. The
      results indicated that R61748 (1 mg/l) decreased the rate of rise of the
      transmembrane action potential (Vmax) by 40% and shortened the action potential
      duration (APD) by 10% in guinea-pig right ventricular papillary muscle. ERP/APD
      increased by 10%. The effect was dose-dependent. Clinical electrophysiologic
      studies (EPS) in 6 patients with ventricular premature beats showed that R61748
      (0.1 mg/kg) prolonged PA duration by 30%, AH interval by 13% and HV duration by
      24%. ECG revealed prolonged P duration by 16%, P-R interval by 16% and QRS
      duration by 17%. R61748 has also been used in 14 patients with idiopathic
      premature ventricular contraction (PVCs). PVCs were abolished in 6 patients and
      decreased more than 93% in 2 patients. The average reduction of PVCs was 80%.
      R61748 (0.075 mg/kg) abolished an episode of repetitive ventricular tachycardia
      in 1 patient. It is concluded that R61748 is a potent new class Ic antiarrhythmic
      agent with slow kinetics. R61748 is the 4-OH metabolite of R54718 (transcainide)
      (Stroobandt et al., 1987) which is a new class Ic antiarrhythmic agent. Up to now
      no reports have been published about R61748. This paper presents the initial
      studies of cellular and clinical electrophysiologic effects and the evaluation of
      antiarrhythmic efficacy of R61748.

PMID- 1378675
TI  - Whipple's disease: the value of upper gastrointestinal endoscopy for the
      diagnosis and follow-up.
AB  - Due to the systemic nature of Whipple's disease the clinical presentation may be
      highly variable. The diagnosis may therefore be unduly delayed. If untreated,
      Whipple's disease is still potentially lethal. In contrast, the endoscopic
      findings as they are observed in the postbulbar small intestine and the light
      microscopic picture of small intestinal biopsies are almost pathognomonic. Out of
      a group of 18 patients (14 male, 4 female, mean age = 45 yrs), 12 patients were
      diagnosed using upper gastrointestinal endoscopy and duodenal biopsy, while six
      patients were diagnosed only by a small intestinal capsule biopsy. The clinical
      history prior to diagnosis lasted from 1 m to 22 yrs (mean = 3 yrs 6 m) in the
      first group and from 4 yrs to 21 yrs (mean = 12 yrs 6 m) in the second group. The
      endoscopic findings at the time of diagnosis were: oesophagitis (1/12), erosive
      gastritis (4/12), atrophic gastritis (2/12), severe erosive bulbitis (3/10),
      pathognomonic post-bulbar duodenal lesions (9/12). In 20% of the patients the
      endoscopic lesions had disappeared 6 m after antibiotics while the lesions had
      disappeared in all cases 9 m after therapy, despite the fact that PAS positive
      macrophages remained present in the endoscopic biopsies for years. All patients
      were treated with antibiotics (8 tetracycline alone, 4 tetracycline, streptomycin
      and penicillin, 6 trimethoprim). Five patients (27%-4 of the tetracycline group)
      relapsed within 2 to 20 yrs after the initial diagnosis. Three of these patients
      (3/5) had typical duodenal lesions on endoscopy at that time.

PMID- 1378676
TI  - Endoscopic palliation of malignant dysphagia.
AB  - In patients with obstructive tumors of the esophagus and who cannot undergo
      curative surgery, endoscopic palliative methods can provide a quick relief of
      dysphagia with subsequent improvement of nutritional status. The technical
      success rate is as high as 95% for intubation and 100% for laser therapy. Both
      methods have their specific indications. Intubation is often able to provide
      quick and definitive palliation while laser therapy requires several sessions and
      relapses of obstruction are frequent. On the other hand, intubation carries a
      high risk of perforation (8.7%), and laser appears to be safer (1.7%
      perforation). Both methods can be combined in many instances, and their
      association with afterloading or external beam radiation therapy can be
      beneficial. Even if the overall survival rate is only 6 to 7 months, the
      improvement of the quality of life is the priority goal of these methods.

PMID- 1378677
TI  - Percutaneous endoscopic gastrostomy.
AB  - From March 87 to March 92, fifty eight patients were referred to our department
      for percutaneous endoscopic gastrostomy (PEG). The modality of the feeding tube
      insertion is described. The most common indications for placement were neurologic
      disorders in 62% of the cases (n = 36) and malignant diseases in 32% (n = 19).
      The success rate of the technique was 98.3% (n = 57). No procedure-related
      mortality was observed. A low rate of major complication (1.7%) and minor
      complication (10.5%) was noted. Feeding tubes were removed in 21% of patients (n
      = 12); none of them with malignant disease. Survival curve analysis demonstrated
      that 50% of patients died within 3 months of PEG placement. Such results raise
      questions about the selection of patients undergoing PEG. Our experience of
      patients undergoing PEG. Our experience suggests that PEG is easy and safe, even
      in debilitated patients, having an acceptable life expectancy.

PMID- 1378678
TI  - Endoscopic stenting for biliary strictures.
AB  - A consensus is growing among units that have an experience in both endoscopic and
      percutaneous stenting techniques that the endoscopic approach of malignant
      biliary strictures is more comfortable for the patient and provides less
      complications. This article describes endoscopic biliary drainage in different
      malignant stenosis of the bile ducts and delineates the respective indications of
      percutaneous and endoscopic techniques together with the possible combination of
      these two methods in selected cases. It also tackles the question of the medical
      surgical approach of the patients, which might, thanks to a better selection,
      reduce the morbidity and mortality associated with surgery. The indications of
      biliary stenting in benign strictures, namely post operative or chronic
      pancreatitis associated biliary stenoses, are also discussed. Recently, new
      materials became available for endoscopic and percutaneous biliary drainage, and
      particularly metallic self expanding stents which might provide a better
      palliation among these patients. If these stents fulfill their promise on longer
      follow-up, they may replace the conventional stenting devices.

PMID- 1378679
TI  - Reaction time in cancer patients receiving peripherally acting analgesics alone
      or in combination with opioids.
AB  - Continuous Reaction Time (CRT) was measured in cancer patients receiving
      peripherally acting analgesics either alone (n = 16) or in combination with
      opioids (n = 16). Comparison was performed matching the patients from each group
      for age and performance status. Statistically significant prolongations of CRT
      and higher sedation scores were seen in the opioid group, while performance
      status did not have any influence on CRT.

PMID- 1378680
TI  - Systematic use of aprotinin in cardiac surgery: influence on total homologous
      exposure and hospital cost.
AB  - To assess the impact of systematic use of aprotinin, 115 consecutive adults
      undergoing cardiac surgery were randomly allocated with a sealed envelope
      technique. Treated (T) patients (n = 58) received 2.10(6) Kallikrein Inactivating
      Units (KIU) before incision, 2.10(6) prior to bypass, and 5.10(5) KIU.hr-1 for 5
      hrs, whereas control (C) cases (n = 57) received nothing. Surgeons,
      perfusionists, ICU and ward physicians were blinded. Postoperative blood loss
      decreased from 1198 ml (C) to 698 ml (T) (p less than 0.001). Total transfusional
      needs were 7.25 (C) and 4.9 (T) units (p less than 0.01), where from 65% were
      autologous in group T, versus 51% in group C (p less than 0.02). Total homologous
      exposure decreased from 4.5 (C) to 2.7 (T) units on the average, from 3 to 1
      units as a median (p less than 0.01). Multiple Stepwise Regression Analysis
      showed treatment as the most important variable influencing postoperative blood
      loss, but duration and type of procedures were more important to explain
      transfusion needs. Both groups were comparable for other pre- and intra-operative
      variables. For coronary operations (n = 75), aprotinin showed the strongest
      negative association with blood loss, the number of arterial conduits being the
      second influencing variable. No evidence was found for increased early graft
      thrombosis. The average hospital bill was 9% lower in the treated group, an
      unexplained finding needing independent confirmation.

PMID- 1378681
TI  - Immunocytochemical localization of alpha-fetoprotein in the developing and carbon
      tetrachloride-treated rat liver.
AB  - The immunocytochemical localization of alpha-fetoprotein (AFP)-producing cells
      was observed in pre- and postnatal and carbon tetrachloride (CCl4)-treated rat
      livers in comparison with that of albumin (ALB)-producing cells. According to
      immunoblotting data, considerable numbers of AFP-positive hepatocytes were
      observed in the differentiating liver between prenatal day 19 and postnatal day 0
      (6 h after birth). Analyses by serial section profiles of these cells revealed
      that certain AFP-positive hepatocytes are also stained with ALB antiserum.
      Immunoelectron microscopy of the AFP-producing cells revealed that immunoreactive
      gold particles are preferentially localized in rough endoplasmic cisternae, Golgi
      apparatus and Golgi-derived vesicles near the cell surface. In addition, the
      release of the content of the Golgi-derived vesicles into the differentiating
      bile canaliculi as well as into the space of Disse by exocytosis is apparent. In
      CCl4-treated rat liver, immunoreactions to AFP are localized exclusively in newly
      formed hepatocytes of the regenerative tissue. These AFP-positive cells have not
      established the hepatic cell cords, and the adjacent ones are conjugated to each
      other mainly by simple attachment devices as in the case of those in pre- and
      postnatal rat liver.

PMID- 1378682
TI  - Different effects of fractionated irradiation on potassium efflux and exocytotic
      amylase release.
AB  - Irradiation of head-neck cancer influences the salivary glands with dryness and
      discomfort for the patients as a consequence. In the present study we used in
      vitro secretory models and morphological characterization of rat parotid gland.
      Irradiation was given as a 5-day schedule with total doses from 20 Gy to 45 Gy.
      Electrolyte secretion (86Rb as indicator for potassium) caused by noradrenaline
      was decreased in correlation to irradiation dose delivered compared to
      controlateral control glands 10 days following irradiation. Noradrenaline
      stimulated exocytotic amylase release was not at all affected, and there were no
      signs of quantitative morphological alterations following irradiation compared to
      control glands. The results indicate that there are differences in radiation
      sensitivity for the two different secretory processes in the salivary glands; the
      structures regulating electrolyte and fluid secretion seem to be more vulnerable
      to irradiation than those regulating exocytosis.

PMID- 1378683
TI  - Effect of the substrate on neurofilament phosphorylation in mixed cultures of rat
      embryo spinal cord and dorsal root ganglia.
AB  - The effect of the substrate on neurofilament phosphorylation was studied in
      primary cultures of spinal cord and dorsal root ganglia dissociated from 15-day
      old rat embryos. On polylysine and Primaria substrates, spinal cord neurons
      formed aggregates connected by bundles of neurites. (Primaria dishes have a
      modified plastic surface with a net positive charge). On both polylysine and
      Primaria substrates, spinal cord neurons were stained with neurofilament
      monoclonal antibodies reacting with phosphorylated epitopes appearing early in
      rat embryo development, i.e. soon after neurofilament expression. Conversely,
      immunoreactivity with antibodies recognizing late phosphorylation events was only
      observed on Primaria substrates. As reported by many investigators, fibronectin
      and laminin were excellent substrates for dorsal root ganglia neurons in culture.
      However, on both laminin and fibronectin substrates immunoreactivity with
      antibodies recognizing late phosphorylation events, was only observed on Primaria
      substrates. As reported by many investigators, fibronectin and laminin were
      excellent substrates for dorsal root ganglia neurons in culture. However, on both
      laminin and fibronectin substrates immunoreactivity with antibodies recognizing
      late phosphorylation events, only occurred after several days in culture, at a
      time when non-neuronal cells (mainly astrocytes) had formed a confluent
      monolayer.

PMID- 1378684
TI  - Increase in endogenous fibrinolysis and platelet activity during exercise in
      young volunteers.
AB  - The influence of physical exercise and intake of oral contraceptives on
      endogenous fibrinolytic activity and platelet aggregation behaviour was studied
      in young healthy women and compared to an age matched group of male volunteers.
      Physical exercise beyond the anaerobic threshold significantly increased the
      activity of tissue-plasminogen activator (t-PA) in male and female volunteers
      from initial values of 1.6 +/- 0.1 and 1.8 +/- 0.2 IU/ml to 5.5 +/- 1.0 and 5.3
      +/- 0.9 IU/ml (P less than 0.01), respectively. In women taking low-dose estrogen
      oral contraceptives t-PA increased from 1.5 +/- 0.2 to 3.8 +/- 0.5 (P less than
      0.01). There were no major alterations in plasminogen activator inhibitor - I
      (PAI-I) plasma activities. Platelet activity during exercise was significantly
      enhanced in male test persons indicated by a significant decrease in the ED50
      values for ADP. In contrast, in women ED50 values were basically unaltered,
      irrespective of the intake of oral contraceptives.

PMID- 1378685
TI  - Effect of prostacyclin analogue iloprost on haemodynamic parameters during femoro
      crural reconstruction.
AB  - A randomised placebo-controlled trial was conducted to investigate the effects of
      iloprost, a stable prostacyclin analogue, on peripheral resistance, graft blood
      flow and mean systemic arterial blood pressure (MABP) during femoro-crural
      arterial bypass. 3000ng of iloprost, infused into the graft, produced an
      immediate drop in peripheral resistance by a mean (range) of 40% (4-80%) (P less
      than 0.01, Wilcoxon). Decreased peripheral resistance persisted to 20 minutes.
      Graft flow during the same period increased by 52% (-7 to 294%) (P less than
      0.01). A transient maximal drop in mean MABP of 22% from 83-65 mmHg occurred 5
      minutes post iloprost infusion but caused no detrimental effects and recovered to
      baseline values by 10 mins. Iloprost produces an immediate decrease in peripheral
      resistance associated with a prolonged increase in graft blood flow. This may
      reduce graft failure in the early postoperative period.

PMID- 1378686
TI  - Fibrinolytic enhancement with a prostaglandin analogue iloprost.
AB  - Earlier workers have suggested a possible fibrinolytic effect using prostaglandin
      or prostaglandin analogues. Despite using maximum tolerated doses of the
      prostaglandin analogue Iloprost, we have been unable to demonstrate any
      significant effect on fibrinolysis in patients with stage IV peripheral vascular
      disease (Fontaine classification).

PMID- 1378687
TI  - Cardioprotection by molsidomine and iloprost in myocardial ischemia in
      anaesthetized cats.
AB  - In ten anaesthetized open chest cats the ligation of left descending coronary
      artery (LLDCA) resulted in 80 percent of mortality with survival time of 40.9 +/-
      8.6 min. The death of animals was preceded by premature ventricular contractions
      which occurred with frequency 7.3 +/- 0.6/min after 2.1 +/- 0.3 min following
      LLDCA. Molsidomine as a dose of 20 micrograms/kg given i.v. to 10 cats 15 min
      before LLDCA affected none of the above characteristics of acute myocardial
      ischemia. The pretreatment with iloprost (2 micrograms/kg given i.v. to 10 cats)
      diminished frequency of premature ventricular contractions and elongated a period
      of time required for their occurrence after LLDCA, however, iloprost was also
      unable to diminish mortality of LLDCA cats. Only a combined administration of
      molsidomine and iloprost significantly diminished mortality among LLDCA cats down
      to 20 percent and doubled their survival time as compared to the controls. It is
      concluded that NO-donors (molsidomine) exert permissive effect towards the
      cardioprotective action of prostacyclin analogues (iloprost) in cats with
      myocardial ischemia. LLDCA cats pretreated with molsidomine + iloprost enjoyed a
      more complete cardioprotection than those pretreated with a high dose (3000
      units/kg i.v.) of superoxide dismutase.

PMID- 1378688
TI  - Iloprost preserves endothelial function against cyclosporin A and sensitises
      microvessels towards endothelium-dependent and -independent vasodilatation.
AB  - The effects of iloprost have been investigated on the endothelial damage produced
      by cyclosporin-A (Cy-A) and on the microvascular reactivity to sodium
      nitroprusside (SNP), acetylcholine (ACh) and isoprenaline (ISO) following
      iloprost treatment i.e. in the absence of effective plasma levels, using the
      hamster cheek pouch. It has been shown that iloprost protects the microvascular
      arteriolar endothelium from functional damage by Cy-A and that iloprost infusion
      for 12-14 hr sensitizes the arterioles to ACh, SNP and ISO, an effect which is
      evident 5 hr but not 24 hr following treatment and in the case of ACh is
      abolished by indomethacin.

PMID- 1378689
TI  - Iloprost in cardiopulmonary bypass procedures.
AB  - The inhibition of platelet aggregation during cardiopulmonary bypass and effects
      on post-operative placebo-controlled study of 145 patients. Significant
      preservation of platelet numbers and function were shown without significant
      haemodynamic problems, but no effect on cerebral deficits could be found. The use
      of iloprost in patients with severe thrombocytopenia seems justified, but the
      clinical benefits from its use in routine cardiopulmonary bypass remain to be
      shown.

PMID- 1378690
TI  - Effects of iloprost and factors affecting outcome in patients with severe
      inoperable lower limb ischaemia. U.K. Severe Limb Ischaemia Study Group.
AB  - The effects of i.v. iloprost given for 14-28 days on six month outcome in
      patients with severe inoperable lower limb ischaemia were investigated in a
      double-blind placebo controlled study. More iloprost patients (64%) survived with
      a viable limb than placebo patients (42%). Iloprost improved prognosis in all
      subgroups of patients, but patients with lower presenting ankle Doppler pressures
      had a worse outcome than patients with higher pressures.

PMID- 1378691
TI  - Pharmacokinetics of intragraft iloprost infusion during femoro-crural
      reconstruction.
AB  - Pharmacokinetics of a single intra-graft infusion of 3000ng iloprost during
      femoro-crural bypass surgery have been investigated. Plasma iloprost
      concentrations, biphasic half-lives, and total drug clearances were found to
      occur within ranges demonstrated for IV infusion dose regimens.

PMID- 1378692
TI  - Synergistic platelet inhibitory effect of the phosphodiesterase inhibitor
      piroximone and iloprost.
AB  - Platelet activity is regulated through synthesis and degradation of the
      intracellular second messengers cAMP or cGMP. The antiplatelet effect of the
      phosphodiesterase (PDE) III inhibitor Piroximone (PIR) was studied in vitro in
      platelet rich plasma. ADP induced aggregation was inhibited by PIR with an IC50
      of 67 +/- 43 microM. The inhibitory effect was time and dose dependent. The
      antiaggregatory effects in vivo were studied in anaesthetised rats. Reduction of
      platelet count following injection of 100 micrograms/kg bw collagen was measured
      after bolus injection of PIR and vehicle. Piroximone bolus 2 mg/kg bw resulted in
      a 50% inhibition of platelet aggregation in rats. Cyclic AMP levels in washed
      platelets rose time and dose dependently after PIR. Coincubation of PDE III
      inhibitor PIR and adenylate cyclase activator Iloprost (ILO) resulted in a
      significant synergistic enhancement of the antiaggregatory effect. The PDE III
      inhibitor PIR exerted an effective inhibition of platelet aggregation in vivo and
      in vitro. The inhibitory effects in vitro were synergistically augmented by the
      prostacyclin analog Iloprost. These platelet inhibitory effects might be of
      clinical importance.

PMID- 1378693
TI  - Effect of prostaglandins and capsaicin on gastric vascular flow and mucosal
      injury in endothelin-1-treated rats.
AB  - Infusion of endothelin-1 reduced vascular flow in the isolated perfused rat
      stomach. Concurrent infusion of iloprost and capsaicin, respectively, did not
      counteract the flow-reduction caused by endothelin-1. Infusion of prostaglandin
      (PG)F2 alpha caused vasoconstriction and significantly augmented the endothelin-1
      induced flow reduction. In vivo, i.v. infusion of endothelin-1 (50 pmol/kg//min
      for 10 min) did not cause gastric mucosal damage, but enhanced injury produced by
      intragastric instillation of 20% ethanol. Intragastric administration of iloprost
      or PGF2 alpha prevented the pro-ulcerogenic effect of endothelin-1. Similarly,
      stimulation of afferent sensory neurons by intragastric capsaicin (0.5 mg/kg)
      protected against damage caused by endothelin-1 and 20% ethanol. Functional
      ablation of afferent sensory neurons by s.c. administration of 125 mg/kg
      capsaicin markedly enhanced gastric mucosal damage by intraluminal 20% ethanol.
      This damage was, however, not further increased by infusion of endothelin-1.
      These findings show that protection against the proulcerogenic effect of
      endothelin-1 can occur without antagonism of vasoconstriction. The findings also
      show that parameters involved in protection such as afferent sensory neurons do
      not contribute to the pro-ulcerogenic effects of endothelin-1 suggesting that
      protection against and potentiation of damage rely on different mechanisms.

PMID- 1378694
TI  - [A clinical evaluation on postprostatectomy incontinence].
AB  - Postprostatectomy incontinence was evaluated in 193 patients, who underwent
      retropubic prostatectomy (RPP) or transurethral resection of the prostate (TURP)
      during the past 5 years from 1985 to 1989 at the Kyoto Prefectural University of
      Medicine. The occurrence rate of postprostatectomy incontinence was 17.2% in the
      patients who had undergone RPP and 33.3% of those who had undergone TURP.
      Although postprostatectomy incontinence disappeared within one week in half of
      the patients, postprostatectomy incontinence remained for more than one month in
      4.9% of the patients who had undergone RPP and 3.3% of those who had undergone
      TURP. The incidence of postprostatectomy incontinence tended to be high in the
      patients of advanced ages. Postprostatectomy incontinence recognized in this
      series was classified into stress incontinence and urgency incontinence groups.
      An analysis of the results of cystometry performed before the operation showed
      that the volume of maximum desire of voiding in the urgency incontinence group
      was smaller than that in the group without postprostatectomy incontinence.
      Furthermore, supposing the urgency degree as a new parameter, which is defined as
      a ratio of first desire of voiding to maximum desire of voiding, the urgency
      degree of the urgency incontinence group was higher than that of the group
      without postprostatectomy incontinence. Patients with an urgency degree higher
      than 70% were found to have a high probability of urgency incontinence. These
      findings suggested that advanced age was the risk factor of postprostatectomy
      incontinence and that a small bladder capacity and high urgency degree were the
      high risk factors of postprostatectomy urgency incontinence.

PMID- 1378695
TI  - Use of endovascular stents to increase pulmonary blood flow in pulmonary atresia
      with ventricular septal defect.

PMID- 1378696
TI  - An immunohistochemical and prognostic analysis of cytokeratin expression in
      malignant uveal melanoma.
AB  - A group of 52 patients with malignant uveal melanoma treated by primary
      enucleation in 1977-1979 was studied to determine the frequency of
      immunoreactivity for cytokeratins (CK) in primary and metastatic melanoma, the CK
      types present, and the prognostic significance of CK expression. By
      immunohistochemistry, monoclonal antibody (MAb) V9 to vimentin reacted with all
      52 formalin-fixed, paraffin-embedded primary tumors and all 31 metastases from 11
      patients. MAb CAM 5.2 to CK 8 and 18 reacted with 20 and MAb CY-90 to CK 18 with
      25 primary melanomas, whereas MAb KS-B17.2 and MAb CK5 to CK 18 labeled 8 and 6
      tumors, respectively. Antibodies to CK 13 and CK 19 each labeled single cells in
      one specimen, and other CK types were not detected. In 6 primary melanomas, only
      a few tumor cells were immunopositive for CK 8 and 18, but in 17 cases up to one
      quarter, and in 2 tumors more than one quarter, of them were labeled. The
      positive cells were spindle, epithelioid, or intermediate in shape, and tended to
      be more frequent in mixed than in spindle cell melanomas. MAbs CAM 5.2 and CY-90
      did not react with any of the 16 liver metastases, but labeled 7 of 15 other
      metastases. Metastases were somewhat more common when the primary tumor was
      immunoreactive for CK 8 and 18, apparently because CKs were more frequent in
      mixed cell melanomas. Although CK expression is of diagnostic significance and
      can denote low levels of epithelioid differentiation, it is not an independent
      prognostic factor in malignant uveal melanoma.

PMID- 1378697
TI  - Alcoholic liver disease. Parenchyma to stroma relationship in fibrosis and
      cirrhosis as revealed by three-dimensional reconstruction and
      immunohistochemistry.
AB  - Severe ethanol-induced liver damage is characterized by fibrous dissociation of
      liver cell plates leading to many apparently isolated hepatocytes. Three
      dimensional reconstruction, however, revealed hepatocytes that were surrounded by
      connective tissue as endpoints of "parenchymal pillars" or in association with
      liver cell plates and bile ductules. Double immunofluorescence studies displayed
      the expression of cytokeratin (CK) 7 in bile ducts, including bile ductules, but
      also in some hepatocytes still organized in liver cell plates. The other bile
      duct, typical CK, namely CK 19, was only detectable in few hepatocytes. However,
      the expression of CK 7 and/or CK 19 was less frequent in hepatocytes that were
      closely associated with bile ductules. CK 7 and CK 19 were also found in some,
      but not all, Mallory bodies. These observations indicate that the expression of
      these two CKs is neither related to a transformation of hepatocytes to bile duct
      like structures ("ductal metaplasia") nor to the formation of Mallory bodies.
      Furthermore, double immunofluorescence studies revealed small groups of
      hepatocytes and bile ductules that were encircled by basement membrane material,
      thus suggesting the formation of "secretory units."

PMID- 1378699
TI  - Spontaneous basophil histamine releasability may not be important in allergic
      disorders.

PMID- 1378698
TI  - Immunohistochemical distribution of lipoprotein epitopes in xanthomata from
      patients with familial hypercholesterolemia.
AB  - Human xanthomas derived from four subjects with familial hypercholesterolemia (3
      homozygotes and 1 heterozygote) were studied by immunohistochemical methods to
      determine the presence and distribution of lipoproteins, which have been
      implicated in the pathogenesis of atherosclerosis. Oxidatively modified low
      density lipoprotein (OxLDL) epitopes detected with anti-OxLDL monoclonal
      antibodies, appeared to have a similar distribution in xanthomata to that of
      macrophages, detected by a cell-specific monoclonal antibody. Double antibody
      labeling with both an anti-macrophage antibody and an anti-OxLDL antibody
      demonstrated that OxLDL epitopes are associated with macrophages and occurred
      intracellularly. Low-density lipoprotein (LDL) epitopes were detected
      extracellularly, with a distribution that was different from that of OxLDL. In
      addition, apo(a) epitopes detected by an apo(a) specific monoclonal antibody, had
      a distribution similar to that of LDL in the dermis and subcutaneous tissues. The
      observed epitope distribution of LDL, OxLDL, or apo(a) was the same regardless of
      the method of treatment of the patients from whom the xanthomas were obtained
      (probucol, simvastatin, LDL apheresis). These findings suggest that OxLDL is
      likely to play a pathogenetic role in the lipid accumulation by macrophages in
      xanthomas, and suggest that Lp(a) also may play a role in their pathogenesis.

PMID- 1378700
TI  - Monitoring of mite Dermatophagoides farinae allergen-specific IgG and IgG
      subclass distribution in patients on immunotherapy.
AB  - House dust mite D. farinae and Der f II-specific IgG and IgG subclass responses
      were evaluated in 32 adults with perennial rhinitis undergoing immunotherapy for
      1 year by means of IgG-RAST and ELISA. The ELISA method, which is based on
      subclass-specific monoclonal antibodies, could detect 0.5-1.5 ng/ml of specific
      antibodies. D. farinae and Der f II-specific IgG4 antibodies increased
      continuously as immunotherapy proceeded, while total IgG and IgG1 antibodies
      reached a plateau value 6 months after the start of immunotherapy, followed by a
      slow decrease during maintenance therapy. During the early phase of treatment the
      concentration of IgG1 and IgG4 antibodies rose, even though the increase of IgG4
      antibodies dominated. The positive clinical outcome as measured by the decrease
      in conjunctival sensitivity was associated with an increased ratio of specific
      IgG4/IgG1 antibodies as well as the magnitude of the IgG4 subclass response.
      Quantitation of IgG subclass antibodies in patients undergoing immunotherapy may
      be of some clinical value, but the clinical usefulness needs to be demonstrated
      for each type of allergen and possibly also for each assay system.

PMID- 1378701
TI  - Detection and molecular weight determination of polyethylene glycol-modified
      hirudin by staining after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis.
AB  - This article describes a general method for detecting pegylated proteins directly
      after SDS-PAGE. The proteins to which polyethylene glycol (PEG) molecules are
      attached are stained with a barium iodide solution. The staining is based on the
      formation of a barium iodide complex with PEG. The described method combines a
      specific staining of PEG molecules with the high resolution of the SDS-PAGE
      method. It is shown that pegylated protein is detectable on SDS-PAGE as well as
      on IEF at concentrations that are not detectable by Coomassie protein staining.
      This paper also describes the determination of the molecular weight of pegylated
      hirudin by calibrating SDS-PAGE with polyethylene glycol of different molecular
      weight. Under the conditions used, PEG showed linear mobility during
      electrophoresis. However, the use of nonpegylated proteins as standards resulted
      in incorrect molecular weight values due to the lower mobility of the pegylated
      protein during electrophoresis. The method described might reflect a general
      method for determining molecular weight of pegylated proteins.

PMID- 1378702
TI  - Laser-induced fluorometric determination of albumin using longwave absorbing
      molecular probes.
AB  - A novel fluorescence assay for HSA is described. It is based on longwave
      absorbing probes that selectively bind to HSA to form fluorescent complexes. The
      two probes reported here (Albumin Blue 633 and Albumin Blue 670) are tailored to
      match the lines of the 633-nm HeNe laser and the 670-nm diode laser,
      respectively. In both cases, the strong laser-induced fluorescence of the
      HSA/probe complexes makes the assay sensitive to HSA at trace levels. Detection
      limits of 0.2 mg/liter were obtained. In addition to its sensitivity, the assay
      is highly selective for HSA in that the response to other serum proteins is
      weaker by a factor of at least 100. It also works well on urine, and no
      significant interferences could be located. Potential interferents are bovine
      serum albumin and some detergents. Parameters of the probe--HSA interaction were
      obtained from a Scatchard evaluation. The high specificity and sensitivity of the
      assay are discussed in terms of molecular geometry of the probes. A photophysical
      mechanism that leads to the effect is proposed. The assay presents a promising
      alternative to immunological determinations of HSA since it is less expensive and
      much more quickly performed.

PMID- 1378703
TI  - A microtiter assay for determining protein, acetylcholinesterase activity, and
      G418 (Neomycin) resistance in cultured cells.
AB  - The Coomassie brilliant blue assay for the determination of protein has been
      extended to rapidly and conveniently measure the protein concentration of cells
      growing in culture in a 96-well microtiter format. Modifications of the standard
      assay include sodium hydroxide to solubilize the cells and ovalbumin, instead of
      bovine serum albumin, as a protein standard. The procedure allows a large number
      of small samples to be assayed simultaneously. Two examples of its use, enzyme
      specific activity and drug resistance, are shown. An assay for
      acetylcholinesterase activity in the same culture plate is demonstrated. G418, an
      inhibitor of cell protein synthesis, is frequently used to select for cells
      transfected with the neomycin resistance gene. The required concentration of G418
      can be easily determined with this protein assay.

PMID- 1378704
TI  - Polymerase chain reaction-aided analysis of gene expression in frozen tissue
      sections.
AB  - A simple method for the detection and localization of mRNA in single frozen
      breast biopsy tissue sections is described. Several extraction procedures were
      compared. Resuspending sections, which could be left at 0 or -70 degrees C for up
      to 20 min in H2O containing RNAse inhibitor, optimally released RNA with minimal
      DNA contamination. Reverse transcription followed by polymerase chain reaction
      amplification using specific primers yielded products visible by ethidium bromide
      staining (abundant sequences) or after Southern blotting (low copy message). We
      found that it was possible, by microdissection, to separate stromal and tumor
      cells and demonstrated differential expression of several genes in the two
      populations. With 40 cycles of amplification, dissected stromal and tumor tissue
      both yielded products encoding glyceraldehyde 3'-phosphate dehydrogenase but only
      the tumor cells gave products with primers specific for either keratin 19, heat
      shock protein 89 alpha or the fig oncogene, which encodes one of the fibroblast
      growth factor receptors that we have recently found to be expressed in breast
      cancers. With refinement of the dissection technique this offers a very sensitive
      analytical tool for measuring and defining the cellular sites of synthesis of low
      abundance message, requiring only single histological sections.

PMID- 1378705
TI  - Replication footprint analysis of cucumber mosaic virus electroporated into
      tomato protoplasts.
AB  - Total RNA extracted from cucumber mosaic virus (CMV) strains WT, with its
      associated satellite CARNA 5 (CMV-associated RNA 5), was successfully
      electroporated into isolated tomato protoplasts. At various time intervals
      samples were extracted for total nucleic acids and analyzed by semidenaturing
      polyacrylamide gel electrophoresis (PAGE). Sequence-specific hybridization probes
      were used for the detection of viral and satellite RNAs following Northern
      transfer. The resulting PAGE patterns and/or autoradiographs depict the
      proportional presence of viral and satellite RNAs in the extracts over time and
      have been referred to as "replication footprint profiles" (RFPs) of specific
      CMV/CARNA 5 combinations. The effective isolation and infection of tomato
      protoplasts, combined with the ability to follow virus/satellite titers during
      the infection by RFP analysis, yield results similar to those of infected plants
      and reduces experiments of 21 or more days in whole plants to less than 72 h in
      protoplasts.

PMID- 1378706
TI  - An assay for acidic peptide substrates of protein kinases.
AB  - The assay of acidic peptides as substrates for protein kinases has not been as
      easy to perform as testing basic peptides or polypeptides. We have developed a
      simple, rapid, and cost-effective procedure that allows the design and testing of
      potential peptide substrates without the constraints imposed by the
      phosphocellulose filter paper method (the need to incorporate positively charged
      residues into the peptide sequence). The technique combines the chelation of 32Pi
      by acid molybdate with PEI-cellulose chromatography. In this way the migration of
      32P-labeled Pi, ATP, and protein are impeded while phosphopeptide is eluted in
      1.5 ml from a 0.25-ml disposable column. In order to validate the assay we used
      two angiotensin II analogues as peptide substrates for the protein tyrosine
      kinase pp60c-src. The assay results using the new procedure were compared to
      those of the phosphocellulose filter paper technique. We also demonstrated the
      use of this method to test linear and cyclic peptides that could not be assayed
      with the phosphocellulose paper technique. This assay will aid those who are
      attempting to determine the substrate specificity of protein kinases.

PMID- 1378707
TI  - Epidural patient-controlled analgesia: an alternative to intravenous patient
      controlled analgesia for pain relief after cesarean delivery.
AB  - Epidural administration of an opioid analgesic by means of a patient-controlled
      analgesia (PCA) system was compared with conventional intravenous PCA for pain
      relief after cesarean delivery. One hundred seventeen healthy women were randomly
      assigned to receive hydromorphone either intravenously (IV-PCA) or epidurally
      (EPI-PCA) after cesarean delivery with epidural bupivacaine for operative
      anesthesia. The hydromorphone requirements were 3.4 and 4.2 times more in the IV
      PCA group on the first (P less than 0.01) and second (P less than 0.01)
      postoperative days, respectively. The mean number (+/- SD) of PCA demands during
      the first 24 h after the operation was 105 (+/- 88) for the IV-PCA group and 33
      (+/- 48) for the EPI-PCA group (P less than 0.01). This difference was also
      significant 24-48 h after surgery. Although the EPI-PCA group utilized
      significantly less opioid medication, pain and sedation scores were similar in
      the two treatment groups; however, a significantly larger percentage of patients
      in the IV-PCA group (46% vs 22%) stated that they felt drowsy during the first
      postoperative day. Pruritus was reported more frequently in the EPI-PCA (67%)
      than in the IV-PCA (33%) group. Nausea was experienced by only 10% of patients in
      the IV-PCA and 6% in the EPI-PCA group. There was no evidence of postoperative
      respiratory depression, with minimal oxygen saturation values of 93% (+/- 3%) and
      94% (+/- 1%) in the IV-PCA and EPI-PCA groups, respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1378708
TI  - Evaluation of a new systolic time interval, the Q-V peak: effects of heart rate,
      contractile state, and loading conditions in dogs.
AB  - The authors investigated the effects of alterations in heart rate, contractility,
      and loading conditions on a newly defined systolic time interval, the Q-V peak,
      in 46 anesthetized dogs. The Q-V peak was measured as the time from the beginning
      of the electrocardiographic Q wave to the moment at which the blood flow rate
      reached its peak in the ascending aorta as determined with an electromagnetic
      flowmeter. The Q-V peak did not change significantly as the heart rate was varied
      by atrial pacing between 70 and 110 beats/minute. The Q-V peak shortened when the
      contractility was augmented with dobutamine (p = 0.0001) and was prolonged when
      it was depressed with propranolol (p = 0.0001). However, the Q-V peak did not
      change significantly when the left ventricular end-diastolic pressure or the mean
      aortic blood pressure was increased to 130% or decreased to 70% of the baseline
      values. These findings suggest that one may also evaluate left ventricular
      performance by measuring the time to systole, which the authors define as the Q-V
      peak.

PMID- 1378709
TI  - Self-stimulation of the ventral tegmental area enhances dopamine release in the
      nucleus accumbens: a microdialysis study.

PMID- 1378710
TI  - Assessment of dopamine release by in vivo microdialysis in the nucleus accumbens
      of rats following acute and chronic administration of desipramine.

PMID- 1378711
TI  - Morphine-induced downregulation of mu-opioid receptors and peptide synthesis in
      neonatal rat brain.

PMID- 1378712
TI  - Purification, reconstitution, and cloning of an NMDA receptor-ion channel complex
      from rat brain synaptic membranes: implications for neurobiological changes in
      alcoholism.

PMID- 1378713
TI  - The giant cell fibroma: a review of 116 cases.
AB  - A survey of 4342 oral pathology reports accumulated over a five-year period was
      performed. Diagnoses were 1090 irritation fibromas and 116 giant cell fibromas. A
      statistical comparison was then made between the giant cell fibromas and the
      irritation fibromas to determine if there were any differences between these two
      lesions with respect to sex or race predilection, age distribution, or location
      in the oral cavity. Finally, various staining techniques were performed on the
      giant cell fibromas in an attempt to ascertain the origin of the giant cells
      present in these lesions. The results will be discussed in this paper.

PMID- 1378714
TI  - Species differences in 5 alpha-androstane-3 beta,17 beta-diol hydroxylation by
      rat, monkey, and human prostate microsomes.
AB  - The 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of 5 alpha-androstane-3 beta,17
      beta-diol by rat prostate microsomes appears to be catalyzed by a single, high
      affinity cytochrome P450 enzyme. In the present study we have examined the
      hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by prostate microsomes
      from cynomolgus monkeys and from normal subjects and patients with benign
      prostatic hyperplasia. Our results suggest that although rat, monkey, and human
      prostate microsomes catalyze the 6 alpha-, 7 alpha-, and 7 beta-hydroxylation of
      5 alpha-androstane-3 beta,17 beta-diol, these pathways of oxidation in monkeys
      and humans are not catalyzed by a single cytochrome P450 enzyme. The ratio of the
      three metabolites was not uniform among prostate microsomal samples from
      individual humans or monkeys. The 6 alpha-hydroxylation of 5 alpha-androstane-3
      beta,17 beta-diol varied independently of both the 7 alpha- and 7 beta
      hydroxylation, which varied in unison. The 6 alpha-, 7 alpha-, and 7 beta
      hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by monkey prostate
      microsomes appeared to be differentially affected by in vivo treatment of monkeys
      with beta-naphthoflavone or dexamethasone. Treatment of a monkey with
      dexamethasone appeared to cause a 2.5-fold increase in both the 7 alpha- and the
      7 beta-hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol without increasing
      the 6 alpha-hydroxylation. The 7 alpha- and 7 beta-hydroxylation of 5 alpha
      androstane-3 beta,17 beta-diol by human and monkey prostate microsomes, but not
      the 6 alpha-hydroxylation, was inhibited by antibody against rat liver NADPH
      cytochrome P450 reductase. Similarly, the 7 alpha- and 7 beta-hydroxylation of 5
      alpha-androstane-3 beta,17 beta-diol by human prostate microsomes, but not the 6
      alpha-hydroxylation, was markedly inhibited (greater than 85%) by equimolar
      concentrations of the imidazole-containing antimycotic drugs ketoconazole,
      clotrimazole, and miconazole. These results suggest that the 7 alpha- and 7 beta
      hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol by monkey and human
      prostate microsomes is catalyzed by a cytochrome P450 enzyme, whereas the 6 alpha
      hydroxylation is catalyzed by a different enzyme which may or may not be a
      cytochrome P450 monooxygenase. The hydroxylation of 5 alpha-androstane-3 beta,17
      beta-diol by prostate microsomes from normal human subjects was quantitatively
      and qualitatively similar to its hydroxylation by prostate microsomes from
      patients with benign prostatic hyperplasia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1378715
TI  - Antigenic properties of keratan sulfate: influence of antigen structure,
      monoclonal antibodies, and antibody valency.
AB  - The influence of (a) antigen structure, (b) type of monoclonal antibody, and (c)
      antibody bivalency on the immunochemical detection and quantification of keratan
      sulfate (KS) from aggrecan has been studied. Apparent KS epitope levels were
      determined by immunoglobulin G (IgG)-enzyme-linked immunosorbent assay (ELISA) in
      preparations of human aggrecan and in a defined series of lower molecular weight
      proteoglycan preparations generated by proteolytic and alkali treatment of
      aggrecan. Gel filtration chromatography showed KS epitope to be preferentially
      detected in the higher molecular weight fragments of the preparations. In single
      KS chains the epitope was detected in the chains of higher M(r). The ability of
      the proteoglycan to inhibit in the IgG-ELISA decreased with a reduction in
      proteoglycan fragment size, ranging between 6- and 260-fold, depending on the
      antibody used. This was considered to be a cooperative binding effect. With most
      antibodies, the sensitivity of the IgG-ELISA (represented by the steepness of the
      inhibition slope) was also reduced with smaller inhibitor sizes. The lowest limit
      of detectability (the amount of KS required to generate 20% inhibition) varied by
      up to 60-fold depending on the antibody used. The use of monovalent Fab fragments
      instead of the whole IgG anti-KS antibody in the ELISA showed that the bivalency
      of the antibody also affected the quantitation of the assay. In the Fab-ELISA the
      assay was found to have an increased detectability (by 9.5-fold with aggrecan as
      the inhibitor), and the proteoglycan fragments and aggrecan all generated
      parallel inhibition curves. Although the Fab-ELISA was somewhat influenced by the
      structural presentation of the KS, this was not apparent for small fragments and
      single chains. Thus the effects of cooperative binding and antibody valency could
      be overcome and quantitative data could be obtained for all samples, using papain
      digested samples and the Fab-ELISA. Application of this assay to analysis of body
      fluids showed the KS-containing fragments in synovial fluid, serum, and urine
      were of different sizes and could be quantified.

PMID- 1378716
TI  - Evidence that swainsonine pretreatment of rats leads to the formation of
      autophagic vacuoles and endosomes with decreased capacity to mature to, or fuse
      with, active lysosomes.
AB  - The plant toxin swainsonine causes a variety of biochemical and morphological
      changes in animal tissues. In rat liver there is an extensive vacuolization which
      is not accompanied by an accumulation of oligosaccharide. In investigating this
      proliferation of autophagic vacuoles we have found that swainsonine
      administration leads to a shift in the density of liver lysosomes as indicated by
      the distribution of several lysosomal glycosidases in sucrose gradients. Whereas
      most of these activities are normally found in low density fractions, only a
      minor portion occurring in high density fractions, the reverse distribution is
      observed after the administration of microgram doses of swainsonine. Two
      promoters of the accumulation of autophagic vacuoles, vinblastine and
      chloroquine, caused the expected increase in very light vacuoles as measured by
      localization of two acid hydrolases. However, this effect of the two agents was
      blocked by swainsonine pretreatment. Moreover, swainsonine decreased the
      degradation of endocytosed asialofetuin and increased the retention of the
      glycoprotein in very light fractions. These results suggest that vesicle movement
      and/or fusion is inhibited by the pretreatment with the toxin. That the effects
      are mediated by a change in vacuolar membrane is suggested by the finding that
      lysosomes prepared from the livers of swainsonine-fed rats are much more fragile
      than control lysosomes, more so in metrizamide solutions than in sucrose
      solutions. The swainsonine may exert its effect through its known ability to
      alter the biosynthesis of complex glycoproteins, which are abundant and
      distinctive in lysosomal membranes.

PMID- 1378717
TI  - Epitope mapping of monoclonal antibodies to the Escherichia coli F1 ATPase alpha
      subunit in relation to activity effects and location in the enzyme complex based
      on cryoelectron microscopy.
AB  - The interaction of Escherichia coli F1 ATPase (ECF1) with several different
      monoclonal antibodies (mAbs) specific for the alpha subunit has been examined.
      The epitopes for each of the mAbs have been localized by using molecular
      biological approaches to generate fragments of the alpha subunit. The binding of
      several of the mAbs has also been examined by cryoelectron microscopy of ECF1 Fab
      complexes. One of the mAbs, alpha II, bound in the region Asn 109-Val 153 without
      affecting ATPase activity. Most of the mAbs bound in the C-terminal third of the
      alpha subunit. MAb alpha 1 bound between residues Gln 443 and Trp 513. This mAb
      activated ATPase activity and was visualized in cryoelectron microscopy,
      superimposed on the alpha subunit, indicating that the epitope was on the top or
      bottom of ECF1 in the hexagonal projection. Other mAbs to the C-terminus,
      including alpha D which also activated the enzyme, reacted between Gly 371 and
      Trp 513 but failed to bind to small overlapping fragments within this sequence.
      The epitopes for these mAbs are probably formed by the folded polypeptide which
      occurs only in Western analysis when long stretches of the alpha subunit are
      present, suggesting that the C-terminus of alpha is a self-folding domain. In
      cryoelectron microscopy, Fab fragments for alpha D were seen extending from the
      sides of the ECF1 complex in hexagonal projection.

PMID- 1378719
TI  - Effect of bufalin and pregnanes on vasoreactivity of human resistance arteries.
AB  - Endogenous Na/K ATPase inhibitory activity has been implicated in salt and water
      homeostasis in mammals and amphibians. Recent interest has focused on endogenous
      cardiac glycosides, some progesterone derivatives (pregnanes) and the amphibian
      bufodienolides. This study has examined the effects of non-planar and planar
      pregnanes and the bufodienolide bufalin on vasoreactivity of human resistance
      arteries. Bufalin and a non-planar pregnane caused concentration-dependent
      potentiation of the tone of submaximally pre-contracted arteries and inhibited
      endothelium-dependent relaxation, whereas a planar pregnane affected neither
      response. The relative potency of the compounds studied suggest the results do
      not simply reflect degrees of Na/K ATPase inhibition. The active compounds may be
      important in the regulation of vascular tone.

PMID- 1378718
TI  - Angiogenesis and rheumatoid arthritis: pathogenic and therapeutic implications.
AB  - Rheumatoid arthritis can be considered as one of the family of 'angiogenesis
      dependent diseases'. Angiogenesis in rheumatoid arthritis is controlled by a
      variety of factors found in the synovial fluid and pannus tissue. Modulation of
      the angiogenic component of the disease may alter the pathogenesis of the
      condition, and subsequent cartilage and joint destruction, by reducing the area
      of the endothelium in the pannus and restricting pannus growth. Current
      therapeutic strategies exert, to varying extents, an inhibitory effect on the
      angiogenic process. In particular, the mode of action of the slow acting
      antirheumatic drugs may be due to their effect on the angiogenic response. The
      development of novel angiostatic treatments for chronic inflammatory joint
      disease may lead to a new therapeutic approach in controlling disease
      progression.

PMID- 1378720
TI  - Two novel monoclonal antibodies to fibronectin that recognize the Hep II and CS-1
      regions respectively: their differential effect on lymphocyte adhesion.
AB  - We have obtained two new mAbs to the carboxy-terminal region of fibronectin,
      namely P3D4 and P1F11, and have studied their binding sites and their ability to
      block lymphocyte adhesion to fibronectin. ELISA and Western blot analyses showed
      that P3D4 reacts with both fibronectin chains and both Hep II-containing
      fragments (58 kDa and 38 kDa). P1F11, raised against the synthetic peptide CS-1,
      reacted with the 38 kDa fragment and with a 190 kDa fragment derived from the A
      chain of fibronectin. P1F11 did not react with the 58 kDa fragment thus clearly
      establishing that 58 kDa comes from the B chain of fibronectin and lacks the CS-1
      sequence. mAbs P3D4 and P1F11 were used to evaluate the contribution of the Hep
      II and CS-1 sites in cell attachment to fibronectin. P3D4 effectively inhibited B
      cell adhesion to 38 kDa, 58 kDa and fibronectin; P1F11 however produced only
      limited inhibition, suggesting that lymphocyte interaction with Hep II may
      modulate further binding to the CS-1 site.

PMID- 1378721
TI  - P-selectin (CD62) binds to subpopulations of human memory T lymphocytes and
      natural killer cells.
AB  - P-selectin (CD62) is a Ca(2+)-dependent lectin expressed on activated platelets
      and endothelium. Although P-selectin is known to function as a receptor for
      myeloid cells, previous studies indicated that P-selectin also bound to a subset
      of lymphocytes. Using a multi-color immunofluorescence assay we found that
      purified P-selectin bound to 12.2 +/- 4.1% of peripheral blood lymphocytes and
      that P-selectin could mediate adhesion of activated platelets to lymphocytes. A
      subpopulation of CD4+, CD8+, and CD16+ lymphocytes bound P-selectin. There was a
      marked preference for P-selectin binding to memory cells (CD45RO+) in both the
      CD4+ and CD8+ populations. Binding to all cell types was Ca(2+)-dependent and
      blocked by pretreatment of the cells with sialidase. These data suggest that P
      selectin may play a role in the recruitment of specific lymphocyte populations to
      sites of inflammation.

PMID- 1378722
TI  - cDNA sequence analysis of CP94: rat lens fiber cell beaded-filament structural
      protein shows homology to cytokeratins.
AB  - To study the molecular structure of the gene responsible for a lens fiber cell
      beaded-filament structural protein of 94kDa (CP94), we isolated its specific cDNA
      from a rat lens cDNA library by use of anti-mouse CP94 antiserum. The expressed
      fusion protein kept the epitopes specific against anti-chick CP97 as well as anti
      mouse CP94 antibody, and the size was estimated as 190-200kDa, indicating that
      the cDNA insert of the clone seemed to encode a polypeptide with 80-90kDa in
      appearance. Northern analysis indicated that CP94 mRNA is expressed only in the
      lens, and not in the brain, skin, heart, kidney, lung, and liver, and the size
      was estimated to 2.1-2.3kb. In a lens of inherited microphthalmic mouse, Elo, a
      trace amount of mRNA with the size closely similar to that of rat mRNA was
      observed. The entire compiled sequence (1,873bp) showed an open reading frame
      covering the sequence of 533 amino acids totalling 58,857Da. No sequence
      homologous to the entire CP94 was found among the entries of any nucleotide and
      amino acid sequence databases; but with respect to a limited amino acid sequence
      of N-side region of CP94, a significant homology with cytokeratins was found.

PMID- 1378723
TI  - Cloning, expression, and characterization of a gene encoding the human
      angiotensin II type 1A receptor.
AB  - The human angiotensin II (AII) type 1a receptor gene and its upstream control
      sequence has been cloned from a human leukocyte genomic library. The promoter
      element CAAT and TATA sequences were found at -602 and -538, respectively,
      upstream from the translational initiation site. The deduced protein sequence is
      homologous to rat and bovine AT1a receptors (94.7% and 95.3% identity). The
      expressed gene exhibited high-affinity AII and Dup753 binding and was
      functionally coupled to inositol phosphate turnover. Northern analysis of human
      tissues showed AT1 receptor mRNA expression in placenta, lung, heart, liver, and
      kidney. Using 5' untranslated and coding sequence as probes in a Southern blot
      analysis, it was established that another AT1 subtype exists in the human genome.

PMID- 1378724
TI  - Human insulin-like growth factor binding protein-6 is O-glycosylated.
AB  - Insulin-like growth factor binding protein-6 is abundant in cerebrospinal fluid
      and has a marked preferential binding affinity for IGF-II over IGF-I. The present
      study demonstrates that IGFBP-6 is O-glycosylated but not N-glycosylated.
      Carbohydrate analysis revealed the presence of approximately 20-30 carbohydrate
      residues/molecule. Galactosamine, galactose and sialic acid were most abundant,
      with glucosamine and fucose present in lower concentrations. Mannose was not
      detected. Enzymatic deglycosylation did not alter the high affinity of IGF
      binding protein-6 for IGF-II (Ka 4.4 +/- 2.2 x 10(11) M-1) or its preference for
      IGF-II over IGF-I. Glycosylation of IGFBP-6 may affect its secretion, in vivo
      stability or localization, but does not affect its ligand binding properties.

PMID- 1378725
TI  - Biosynthesis of nitric oxide and citrulline from L-arginine by constitutive
      nitric oxide synthase present in rabbit corpus cavernosum.
AB  - The objective of this study was to determine whether a constitutive isoform of
      nitric oxide (NO) synthase is present in rabbit corpus cavernosum that could
      account for the involvement of the L-arginine-NO pathway in neurogenically
      elicited relaxation of the corpus cavernosum and, therefore, penile erection.
      Citrulline was determined by monitoring the formation of 3H-citrulline from 3H-L
      arginine. NO was determined by monitoring the formation of total NO(x)
      (NO+nitrite [NO2-]+nitrate [NO3-]) by chemiluminescence after reduction of NO(x)
      to NO by acidic vanadium (III). Equimolar quantities of NO plus citrulline were
      generated from L-arginine and the formation of both products was time-dependent
      at 37 degrees C. NO synthase activity was distributed almost entirely to the
      cytosolic fraction. Enzymatic activity was completely dependent on NADPH,
      calmodulin, and calcium. Addition of tetrahydrobiopterin increased NO synthase
      activity by about 30 percent. The NO synthase inhibitor NG-nitro-L-arginine,
      abolished enzymatic activity. The Km for L-arginine was 17 microM and the Vmax of
      the reaction was 18 pmol/min/mg protein. These observations indicate that a
      cytosolic, constitutive isoform of NO synthase, like that found in brain neuronal
      tissue, is present in rabbit corpus cavernosum.

PMID- 1378726
TI  - Action of endothelin-1 on rat astrocytes through the ETB receptor.
AB  - We investigated the effect of ET-1 on the state of rat cerebral astrocytes (AC)
      differentiation. AC ceased to proliferate and changed into its differentiated
      state by treatment with dibutyryl cyclic AMP (DBcAMP). The cell growth activity
      in DBcAMP-treated AC was stimulated by ET-1 in a dose-dependent manner. Over
      similar dose ranges, ET-1 suppressed the glutamine synthetase activity in DBcAMP
      treated AC. The molar potency of ET-1 in this action was at least 3 orders of
      magnitude higher than that in mitogenic action in AC under the proliferative
      state previously reported. Northern blot analysis revealed that ETB receptor mRNA
      level in DBcAMP-treated AC was markedly higher than that in AC untreated with
      DBcAMP. Consistently, binding studies showed that the Bmax value for [125I]ET-1
      in DBcAMP-treated AC was 16 times higher than that in AC untreated with DBcAMP.
      These results suggest that ET-1 potently induced a retraction of the
      differentiation state of AC from fully the specialized state and that the high
      responsiveness of differentiated AC to ET-1 was partly attributed to the high
      level expression of the ETB receptor.

PMID- 1378727
TI  - Epinephrine induces association of pp60src with Gi alpha in human platelets.
AB  - Using specific antibodies against the alpha subunit of the inhibitory GTP-binding
      protein Gi, we analyzed the association of Gi alpha with other cellular
      components in human platelets. Three tyrosine phosphorylated proteins with
      molecular mass of 63, 58, and 55 kDa were specifically associated with Gi alpha
      in resting platelets. Stimulation of platelets with epinephrine, but not with
      thrombin, induced an increase of the reactivity of the 63- and 55-kDa proteins to
      anti-phosphotyrosine antibodies on western blotting. By in vitro kinase assay we
      found that epinephrine induced the association of kinase activity with Gi alpha
      and that the 63-kDa protein was phosphorylated by this activity. The association
      of kinase activity with Gi alpha in epinephrine-stimulated platelets paralleled
      the association of pp60src with Gi alpha, as detected by western blotting
      analysis using specific anti-pp60src monoclonal antibodies. The interaction of
      pp60src with Gi alpha may play a role in the mechanism of platelet activation by
      epinephrine or in the epinephrine-induced potentiation of the action of other
      platelet agonists.

PMID- 1378728
TI  - Nitric oxide mediates tumor necrosis factor-alpha cytotoxicity in endothelial
      cells.
AB  - Tumor necrosis factor alpha (TNF-alpha) exerts multiple actions on endothelial
      cells including among others the expression of pro-coagulant activity and
      adhesion molecules, and secretion of cytokines. We now show that TNF-alpha
      induces a time- and dose-dependent cytotoxic effect on cultured bovine aortic
      endothelial cells. This TNF-induced cytotoxicity, which is preceded by increased
      production of nitric oxide (NO), is significantly decreased by the NO synthase
      inhibitor N-iminoethyl-L-ornithine (L-NIO). Dexamethasone, which prevents the
      expression of cytokine-induced NO synthase in endothelial cells, also inhibits
      TNF-alpha-dependent cytotoxicity. The results indicate that NO is involved in the
      cytotoxic effect of TNF-alpha on endothelial cells.

PMID- 1378729
TI  - A gradient in expression of the Escherichia coli heat-stable enterotoxin receptor
      exists along the villus-to-crypt axis of rat small intestine.
AB  - Binding of Escherichia coli heat-stable enterotoxin to its receptor is critical
      to the initiation of toxin-induced secretion and diarrheal disease; it is also
      likely, however, that this receptor binds an endogenous ligand. In order to
      characterize the expression of the heat-stable enterotoxin receptor in the small
      intestine, we isolated epithelial cells from villus tip to crypt in rat jejunum
      and ileum. Binding of radiolabeled toxin was maximal in the villus preparations
      and gradually decreased along the villus-to-crypt axis, paralleling the decline
      of sucrase activity. Northern blots of total RNA identified a single heat stable
      enterotoxin receptor transcript (3.8 kb), predominantly in the villus cell
      fractions. In situ hybridization demonstrated clear signal in the villus cells
      with no apparent signal in the crypt cells, lamina propria or muscularis.
      Expression of this receptor was greatest after enterocytes leave the
      proliferative cycle and enter villi. This pattern of gene and protein expression
      may reflect a role of this receptor in binding endogenous ligands which in turn
      may regulate intestinal ion flux along the villus-to-crypt axis.

PMID- 1378730
TI  - Glucagonlike peptide-1(7-36)amide suppresses glucagon secretion and decreases
      cyclic AMP concentration in cultured In-R1-G9 cells.
AB  - We previously reported that GLP-1(7-36)amide had glucagonostatic action as well
      as insulinotropic action in the perfused rat pancreas. In this study, we examined
      the effect of GLP-1(7-36)amide on glucagon secretion and cAMP concentration in
      glucagon-secreting cell line, In-R1-G9. GLP-1(7-36)amide (1nM) significantly
      suppressed glucagon secretion and decreased cAMP concentration in the cells. GLP
      1(1-37) did not affect glucagon secretion. It is suggested that inhibitory effect
      of GLP-1(7-36)amide on glucagon secretion is at least partly mediated by
      adenylate cyclase system.

PMID- 1378731
TI  - Cloning and expression of rat preproendothelin-3 cDNA.
AB  - We report here the cloning and expression of a rat full-length cDNA encoding
      preproendothelin-3 (preproET-3). The predicted rat preproET-3 consisted of 167
      amino acid residues. As in other ET-family peptides, the mature rat ET-3 was
      predicted to be produced through unusual processing from a 41-residue
      intermediate, the big ET-3 in rat. Transient transfection of COS-7 cells with the
      cloned preproET-3 cDNA resulted in the production of mature ET-3 and this
      production was inhibited by phosphoramidon, a metaloprotease inhibitor. This
      suggested that a phosphoramidon sensitive mechanism was involved in the
      production of ET-3 in the transfected COS-7 cells. Northern blot analysis showed
      that an approximately 3.0-kb rat preproET-3 mRNA was expressed in rat tissues,
      including the eye ball, submandibular gland, brain, kidney, jejunum, stomach and
      spleen. A 2.0-kb and a 3.3-kb mRNA were also detected in the eye ball and small
      intestine, respectively. The distinct distribution of rat preproET-3 mRNA from
      that of preproET-1 mRNA suggested that ET-1 and ET-3 played different roles.

PMID- 1378732
TI  - Zervamicins, a structurally characterised peptide model for membrane ion
      channels.
AB  - Voltage dependent membrane channels are formed by the zervamicins, a group of
      alpha-aminoisobutyric acid containing peptides. The role of polar residues like
      Thr, Gln and Hyp in promoting helical bundle formation is established by
      dramatically reduced channel lifetimes for a synthetic apolar analog. Crystal
      structures of Leu1-zervamicin reveal association of bent helices. Polar contacts
      between convex faces result in an 'hour glass' like arrangement of an aqueous
      channel with a central constriction. The structure suggests that gating
      mechanisms may involve movement of the Gln11 carboxamide group. Gln3 may play a
      role in modulating the size of the channel mouth.

PMID- 1378733
TI  - Identification of water-soluble proteases in myelin preparations.
AB  - Sodium chloride extracts obtained from purified bovine brain myelin were found to
      contain proteolytic activity capable of degrading isolated myelin basic protein
      as assessed by SDS gel electrophoresis. Using gels copolymerized with gelatin as
      substrate, two bands at about 54 and 117-125 KDa, respectively, were detected.
      Activity corresponding to the 54 KDa band was inhibited by zinc. Data presented
      in this article suggest that proteolytic activity can be released from the myelin
      sheath in water-soluble form and recognize MBP as substrate.

PMID- 1378734
TI  - Characterization and immune response of a protein produced by a cDNA clone of
      foot and mouth disease virus, type Asia 1 63/72.
AB  - A 0.9 kb double stranded cDNA of foot and mouth disease virus (FMDV) Type Asia 1,
      63/72 was cloned in an expression vector, pUR222. A protein of 38 kd was produced
      by the clone which reacted with the antibodies raised against the virus. A 20 kd
      protein which may be derived from the 38 kd protein contained the antigenic
      epitopes of the protein VP1 of the virus. Injection of 10-20 micrograms of the
      partially purified 38 and 20 kd proteins or a lysate of cells containing 240
      micrograms of the proteins elicited high titers of FMDV specific antibodies in
      guinea pigs and cattle respectively. Also, at these concentrations, the proteins
      protected 5 of 8 guinea pigs and 3 of 8 cattle when challenged with a virulent
      virus.

PMID- 1378735
TI  - 10Sa RNA: processing by and inhibition of RNase III.
AB  - Characterization of the maturation of precursor 10Sa RNA revealed that RNase III
      processed p10Sa RNA to two intermediate molecules. We showed that the
      intermediates are not conformers and both are larger than the mature 10Sa RNA.
      Cell extracts further process the RNase III products to an RNA molecule which has
      a different conformation than 10Sa RNA but is approximately the same size as 10Sa
      RNA. An inhibitor of p10Sa RNA processing by RNase III was identified. It is a
      protein, with a molecular mass of approximately 17 kDa.

PMID- 1378736
TI  - Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA.
      Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues.
AB  - gamma-Glutamyltransferase (GGT, EC 2.3.2.2) is an enzyme involved in glutathione
      metabolism and drug and xenobiotic detoxification. Using human hepatoma Hep G2
      GGT cDNA as probe, we isolated a cDNA from a human pancreatic cDNA library.
      Analysis of the nucleotide sequences revealed a 2244-bp insert that includes an
      open reading frame of 1710 bp, encoding a protein identical to the Hep G2 and
      human placenta GGTs. Similarly, the 5' untranslated region, though shorter, is
      highly homologous to that of Hep G2 cDNA. These data suggest strongly that the
      same gene encodes human GGT in the placenta, Hep G2 and the pancreas. We further
      studied the distribution of the corresponding mRNA, called type I mRNA, in
      different human tissues. Using a highly sensitive method associating reverse
      transcription with specific amplification by polymerase chain reaction, cDNA was
      synthesized from total RNA isolated from the tissues and GGT specific fragments
      were amplified. We observed the presence of a specific cDNA fragment
      corresponding to the type I mRNA in the human tissues and cells tested, providing
      the evidence for a ubiquitous expression of this GGT mRNA in human tissues.

PMID- 1378737
TI  - Biochemical modulation of 5-fluorouracil with leucovorin or delayed uridine
      rescue. Correlation of antitumor activity with dosage and FUra incorporation into
      RNA.
AB  - Two strategies for modulation of 5-fluorouracil (FUra) activity were compared in
      vivo in advanced murine CD8F1 breast tumors with regard to three parameters:
      chemotherapeutic activity, inhibition of thymidylate synthase (TSase) activity,
      and incorporation of FUra into RNA, (FU)RNA. Inhibition of TSase by FUra was
      modulated by leucovorin (LV), and the incorporation of FUra into RNA was
      increased by the administration of otherwise lethal doses of FUra followed by
      uridine "rescue". Thymidylate synthase activity was inhibited substantially (49%)
      by low-dose FUra at 25 mg/kg, but was not further enhanced (48%) by repeated
      daily treatments at the same dose (FUra25 x 4). Inhibition of TSase was somewhat
      enhanced (55%) by the addition of LV to FUra25 x 4, and a greater therapeutic
      effect was obtained with FUra25 x 4 + LV over FUra25 x 4 alone. FUra as a single
      agent at the maximum tolerated weekly dose of 100 mg/kg inhibited TSase activity
      66-73%. This inhibition was further enhanced slightly by the addition of LV (71
      82%), and its therapeutic efficacy was greater than with FUra25 x 4 with or
      without LV. However, in contrast to low dose FUra25 x 4, the antitumor effect of
      FUra100 was not enhanced by LV. (FU)RNA increased with FUra dose from 0.4
      (FUra25) to 2.2 nmol/mg DNA (FUra100). At a very-high-dose of FUra (200-225
      mg/kg) followed by uridine "rescue", TSase inhibition was not further enhanced,
      but both (FU)RNA (4.8 nmol/mg DNA) and the therapeutic efficacy were increased.
      Since TSase could not be further inhibited at doses above FUra100, the increased
      chemotherapeutic efficacy correlated with increased (FU)RNA.

PMID- 1378738
TI  - Inhibition of human immunodeficiency virus type 1 reverse transcriptase by 3'
      blocked oligonucleotide primers.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (EC
      2.7.7.49) with a high specific activity has been purified from the overexpressing
      Escherichia coli strain DH5 alpha [pJS3.7]. Steady-state kinetics of DNA
      synthesis catalysed by RT were analysed on polyriboadenylate 20-mer of (3'
      5')deoxythymidylate [poly(rA).(dT)20] and polyribouridylate 20-mer of (3'-5')
      deoxyadenylate [poly(rU).(dA)20] homopolymeric template-primers. Km values of 40
      and 140 nM (3'-OH ends) and kcat values of 4 and 0.14 sec-1 were determined for
      the two different substrates. Oligonucleotide primers (dA)20 and (dT)20 were
      elongated in a terminal transferase-catalysed reaction (EC 2.7.7.31) with ddATP,
      3'-dATP (cordycepin), 2',3'-epoxy-ATP and arabino-ATP; and ddTTP, 3'-azido-TTP,
      3'-dUTP, 3'-F-dTTP and rUTP, respectively. The resulting oligonucleotides were
      hybridized to their complementary templates and the inhibitory potential of these
      compounds towards DNA synthesis started from unchanged primers was measured.
      Oligonucleotides with unextendable 3'-groups were shown to act as strong
      inhibitors of DNA synthesis catalysed by HIV-1 RT. In particular, poly(rA).(dT)20
      [ddTMP] and poly(rU).(dA)20-[3'-dAMP] were potent competitive inhibitors,
      displaying Ki values of about 6 and 12 nM, respectively. Also 3'-azido-, and 3'
      fluoro-terminated oligonucleotides showed competitive inhibition with inhibition
      constants in the range of 20-35 nM. In contrast, 2',3'-epoxy-terminated (dA)21
      displayed a mixed-type inhibition with a Ki value of 67 nM. Arabino-terminated
      (dA)21 was found to be an uncompetitive inhibitor of HIV-1 RT with an inhibition
      constant of 318 nM. Arabino-terminated primers did not act as strict chain
      terminators because they could be elongated by HIV-1 RT. This study provides
      information on the structure-activity relationship of modified 3'-termini of
      primer molecules which might be exploited as inhibitors of HIV in the future.

PMID- 1378739
TI  - The metabolism of glyceryl trinitrate to nitric oxide in the macrophage cell line
      J774 and its induction by Escherichia coli lipopolysaccharide.
AB  - The metabolism of glyceryl trinitrate (GTN) to nitric oxide (NO) was studied in
      the mouse macrophage cell line J774 and in the human monocytic cell line U937 in
      the absence or presence of Escherichia coli lipopolysaccharide (LPS). Two
      bioassay systems were used: inhibition of platelet aggregation and measurement of
      cGMP after stimulation by NO of guanylate cyclase in J774 cells. In addition, NO
      produced from GTN by cells or by cellular fractions was measured as nitrite (NO2
      ) one of its breakdown products. J774 cells (1.25 x 10(5) cells) treated with
      indomethacin (10 microM) enhanced the platelet inhibitory activity of GTN (22-352
      microM) but not that of sodium nitroprusside (4 microM). This effect was
      abrogated by co-incubation with oxyhaemoglobin (oxyHb, 10 microM) indicating
      release of NO from GTN. U937 cells (up to 60 x 10(5)) did not metabolize GTN to
      NO. LPS (0.5 micrograms/mL for 18 hr) enhanced at least 2-fold the capacity of
      J774 cells but not that of U937 cells to form NO from GTN and this enhancement
      was attenuated when cycloheximide (10 micrograms/mL) was incubated together with
      LPS. In the absence of LPS stimulation, cycloheximide had no effect. Furthermore,
      when incubated with GTN (200 microM), J774 cells treated with LPS released more
      NO from GTN as indicated by a 3-fold greater increase in their level of cGMP
      which was prevented by oxyHb (10 microM). Incubation of J774 cells with GTN (75
      600 microM) for 30 min led to a concentration-dependent increase in NO2- which
      was substantially reduced when the cells were boiled. The microsomal fraction was
      more potent than the cytosol in producing NO2- from GTN (1.2-2.4 mM). Release of
      NO2- from GTN by J774 cells was not affected by treating the cells with the NO
      synthase inhibitor, NG-monomethyl-L-arginine (MeArg, 300 microM). In J774 cells
      made tolerant to GTN, potentiation of the anti-platelet effects of GTN (11-352
      microM) and release of NO2- from GTN was reduced. Thus, J774 cells but not U937
      cells convert GTN to NO. This enzymic pathway (present mainly in the microsomal
      fraction of the J774 cells) is induced by LPS and is not regulated by endogenous
      NO released from L-Arg by the enzyme NO synthase. Furthermore, when compared to
      normal cells, tolerant J774 cells metabolize GTN to NO less effectively as
      assessed by a reduced capacity to potentiate the anti-platelet effect of GTN and
      to release NO2-.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1378740
TI  - Stimulatory effects of insulin and insulin-like growth factor I on migration and
      tube formation by vascular endothelial cells.
AB  - The effects of insulin and insulin-like growth factor I (IGF-I) on migration,
      proliferation and tube-forming activity of endothelial cells were investigated,
      by using bovine carotid artery endothelial cells. Migration was assayed by a
      filter membrane technique and tube formation was assayed by a quantitative
      angiogenesis in vitro model which we have recently developed. In this model,
      endothelial cells are cultured between two layers of type I collagen gel and
      become organized into tube-like structures which mimic capillaries in vivo
      ultrastructurally. Insulin (50-1000 microunits/ml) and IGF-I (10-200 ng/ml)
      significantly stimulated migration of endothelial cells in a dose-dependent
      manner with a maximal stimulation of 3.0-fold at 1000 microunits/ml for insulin
      and 3.8-fold at 200 ng/ml for IGF-I (P less than 0.01). Insulin at concentrations
      up to 1000 microunits/ml and IGF-I up to 100 ng/ml did not affect proliferation
      of endothelial cells. When insulin or IGF-I was added in culture medium on
      collagen gels, tube-forming activity of endothelial cells was markedly
      stimulated. The specific lengths of tubes significantly increased with the
      increase in insulin concentration from 25 to 100 microunits/ml (P less than
      0.01). At 100 microunits/ml, the stimulation was 1.77-fold (P less than 0.01).
      IGF-I (1-100 ng/ml) also stimulated the elongation of tubes dose-dependently with
      a maximal stimulation of 1.96-fold at 100 ng/ml (P less than 0.01). Thus, insulin
      and IGF-I at pathophysiological concentrations stimulate migration and tube
      forming activity of endothelial cells, suggesting that these polypeptides may
      stimulate repair of endothelial injury in cases such as atherosclerosis and may
      act as a stimulator of angiogenesis.

PMID- 1378741
TI  - The human carotid atherosclerotic plaque stimulates angiogenesis on the chick
      chorioallantoic membrane.
AB  - The chick chorioallantoic membrane was used to determine whether the carotid
      atherosclerotic plaque stimulates angiogenesis. Carotid endarterectomy specimens
      (1 mm3) with fibromuscular plaque (n = 8) and complicated plaque (n = 11) were
      implanted on the membrane on day nine of incubation and the response evaluated on
      day 11. Following fixation in situ with 10% formalin the angiogenic response was
      evaluated by: (1) examining whole membrane mounts, (2) quantitatively from a
      vascular density index and (3) from a histological study. Unmanipulated
      chorioallantoic membrane (n = 11) and plaque boiled prior to implantation (n = 6)
      served as controls. The vascularity of whole mounts of both fibromuscular and
      complicated plaque was greater than the controls. Vessel density of the membrane
      was estimated by counting the number of vessels intersecting four concentric
      circles (144.5 mm total circumference) placed on the formalin fixed membrane. The
      vascular density index due to the fibromuscular plaque (390.6 +/- 8.3) and
      complicated plaque (391.0 +/- 14.9) were similar (P greater than 0.9) but were
      significantly greater (P less than 0.001) than the unmanipulated membrane (327.9
      +/- 5.6) or after treatment with the boiled plaque (283.8 +/- 15.6). Transforming
      growth factor beta 1 confirmed the validity of the experimental model to study
      angiogenesis. The histology of the chorioallantoic membrane due to either type of
      plaque was similar. Numerous vessels surrounded the plaque, and intraplaque
      vessels containing nucleated chick erythrocytes were observed. Although scattered
      vessels surrounded the boiled plaque, intraplaque vessels were not observed. This
      study demonstrates that the atherosclerotic plaque has angiogenic properties that
      may account for the increase in vasa vasorum that is associated with the plaque.

PMID- 1378742
TI  - Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I
      indicate the relative importance of IGF-binding protein and receptor binding for
      enhanced biological potency.
AB  - An efficient expression system in Escherichia coli for several biologically
      active insulin-like growth factor-I (IGF-I) fusion peptide analogues is
      described. These novel IGF-I fusion protein analogues have properties that make
      them very useful reagents in the investigation of IGF-I action. The analogues
      comprise an IGF-I sequence and the first 11 amino acids of methionyl porcine
      growth hormone (pGH) and include [Met1]-pGH(1-11)-Val-Asn-IGF-I, which contains
      the authentic IGF-I sequence, and two analogues, [Met1]-pGH(1-11)-Val-Asn-[Gly3]
      IGF-I and [Met1]-pGH(1-11)-Val-Asn-[Arg3]-IGF-I, where Glu-3 in the human IGF-I
      sequence has been replaced by Gly or Arg respectively. The three peptides are
      referred to as Long IGF-I, Long [Gly3]-IGF-I or Long [Arg3]-IGF-I depending on
      the IGF-I sequence present. Production of the purified fusion peptides was aided
      by folding the reduced and denatured fusion peptide sequence under conditions
      that gave very high yields of biologically active product. Introduction of a
      hydrophobic N-terminal extension peptide appears to facilitate the correct
      folding of the IGF-I analogues compared with that obtained previously when
      folding normal-length IGFs. The biological activities of the IGF-I fusion
      peptides were compared with authentic IGF-I and the truncated analogue, des(1
      3)IGF-I. In L6 rat myoblasts, all the analogues were more potent than authentic
      IGF-I in their abilities to stimulate protein and DNA synthesis and inhibit
      protein breakdown. In H35 hepatoma cells, where the IGFs act through the insulin
      receptor, the Long IGF-I analogues maintained a similar potency relative to IGF-I
      as was observed in the L6 myoblasts. The order of biological potency in cell
      lines secreting IGF-binding proteins (IGFBPs) into the medium was Long [Arg3]-IGF
      I-des(1-3)IGF-I greater than Long [Gly3]-IGF-I greater than Long IGF-I greater
      than IGF-I. In chicken embryo fibroblasts, a cell line that does not secrete
      detectable IGFBPs into the medium, Long [Arg3]-IGF-I, was less potent than IGF-I.
      Investigation of receptor and IGFBP association by these analogues reinforced our
      previous findings that N-terminal analogues of IGF-I show increased biological
      potency due to changes in the degree of their IGFBP interactions.

PMID- 1378743
TI  - Expression of the genes for alpha inhibin, beta A inhibin and follistatin in the
      ovaries of Booroola ewes which were homozygotes or non-carriers of the fecundity
      gene FecB.
AB  - Ovine cDNA probes for the alpha and beta A inhibin subunits and for follistatin
      were used to investigate the mRNA species for these hormones in ovaries obtained
      during the luteal phase of the oestrous cycle, from Booroola ewes which were
      homozygous carriers (BB) or non-carriers (++) of the FecB gene. BB ewes had
      significantly higher concentrations of peripheral FSH and LH immunoreactivity
      than ++ ewes, but the peripheral inhibin immunoreactivity and ovarian inhibin and
      progesterone secretion rates were not significantly different between genotypes.
      No gene-specific differences in the number or size of mRNA transcripts detected
      by Northern blotting were noted for any of these genes. A single alpha inhibin
      mRNA species at 1.5 kb was observed in the follicle RNA from ++ and BB ovaries.
      Low amounts of alpha inhibin hybridization were discerned occasionally in ++ and
      BB stroma and also in BB, but not in ++, corpora lutea. The beta A inhibin gene
      was expressed only in the follicles from both ++ and BB ovaries. At least three
      beta A inhibin transcripts were observed; one at 7.5 kb and at least two between
      1.4 and 5.0 kb. The follistatin cDNA probe detected two major transcripts at 2.7
      and 1.5 kb and a minor band at 0.5 kb in both follicle and corpora lutea RNA.
      Densitometry of the Northern blots revealed no significant gene-specific
      differences in the levels of alpha inhibin and follistatin gene mRNA
      transcripts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378744
TI  - Increased calcitonin gene-related peptide- and cholecystokinin-like
      immunoreactivities in spinal motoneurones after dorsal rhizotomy.
AB  - Possible changes in neuropeptides within the ventral horn of the spinal cord were
      investigated after unilateral dorsal rhizotomy at the lumbar level (L1-L6) in
      adult rats. Ten days after the surgery, immunohistochemical observations and
      radioimmunological determinations confirmed a marked loss of calcitonin gene
      related peptide (CGRP)- and substance P (SP)-like immunoreactivities within the
      superficial layers of the deafferented dorsal horn, as expected from the
      degeneration of primary afferent fibres containing these peptides. A concomitant
      increase in immunohistochemical staining and levels of CGRP (+296%) and CCK
      (+71%)-like immunoreactivities was observed in the ipsilateral ventral horn where
      both peptides are located in motoneurones. In contrast, substance P-like
      immunoreactivity that is confined to fibres and terminals within the ventral
      horn, was not altered by dorsal rhizotomy. These data indicate that the
      expression of neuropeptides in spinal motoneurones can be influenced by primary
      afferent inputs.

PMID- 1378745
TI  - The effect of tachykinins on sheep bronchomotor tone.
AB  - The mammalian tachykinin neuropeptides substance P (SP) and neurokinin A (NKA)
      are present in the airways of several species and are involved in control of
      bronchomotor tone. We investigated the effect of SP and NKA on various
      respiratory and cardiovascular parameters in anaesthetized sheep. Dose-dependent
      decrease in dynamic compliance (Cdyn) and increase in respiratory resistance (RL)
      occurred with intravenous administration of SP. The predominant effect of NKA was
      on Cdyn with little or no effect on RL. Consequently SP is a more potent
      bronchoconstrictor than NKA in the sheep and affects both central and peripheral
      airway tone. The sensitivity to SP and NKA and the order of potency found
      suggests the NK-1 receptor predominates in sheep airways. Atropine and the
      ganglion blocker hexamethonium markedly reduced the bronchoconstriction caused by
      SP. SP and NKA were equipotent in causing a significant reduction in respiratory
      rate. SP caused a fall in mean blood pressure while NKA caused mild
      vasoconstriction. Neither peptide affected heart rate. We concluded that SP is a
      more potent bronchoconstrictor than NKA in the sheep and that the mechanism of
      action is mainly indirect involving modulation of postganglionic cholinergic
      nerve endings.

PMID- 1378746
TI  - Unconventional fractionation for palliative radiotherapy of urinary bladder
      cancer. A retrospective review of 94 patients.
AB  - Ninety-four urinary bladder cancer patients with locally advanced, recurrent or
      metastatic urinary bladder cancer were treated with external radiotherapy with
      the aim of palliating local disease. Conventional radical radiotherapy was
      inappropriate because of extensive disease, poor general condition or old age of
      the patients. The palliative course studied was 30 Gy (mid-point dose) in six
      fractions, two fractions a week. Eighty-two patients (87%) tolerated treatment as
      planned. Forty patients (43%) had complete palliation of initial symptoms. Thirty
      eight patients (40%) had initial local control of the tumour, which was lasting
      in 25 cases (26%). Median disease-specific survival of the patients was 13.3
      months. The estimated five-year survival was 13% and survival from bladder cancer
      27%.

PMID- 1378747
TI  - [Changes in monoamine metabolites measured by in vivo microdialysis of the
      brainstem following experimental subarachnoid hemorrhage in rats].
AB  - We investigated the function of monoaminergic neuron in the brainstem by
      measuring its metabolites using in vivo microdialysis following experimental
      subarachnoid hemorrhage in rats. Dialysis probe was implanted into the nucleus
      tractus solitarius (NTS) and continuous perfusion was then started. The
      perfusates were collected every 10-20 minutes and assayed by high-performance
      liquid chromatography (HPLC) with electrochemical detection (ECD). The main
      monoamine metabolites in extracellular space measured in NTS were 3,4-dihydroxy
      phenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic
      acid (5-HIAA). The extracellular content of DOPAC was abruptly increased after
      cisternal autologous blood (0.3ml) injection, reached a peak at 20-40 minutes,
      and then decreased over 120 minutes. The content of HVA and 5-HIAA changed as
      well as DOPAC. These results showed non-specific response for ischemia of the
      brainstem, because the similar changes were seen after cisternal saline
      injection. The disappearance rate of monoamine metabolites after pargyline
      administration (75 mg/kg, i.p.) at various time periods after cisternal blood
      injection was most rapid at 2 days after SAH and recovered gradually. In
      particular the decline curve of DOPAC consisted of two compartments and early
      compartment was disturbed more severely than late compartment. These results
      indicate that the functional disturbance of nerve terminals is more severe than
      nerve cell body in adrenergic neurons.

PMID- 1378748
TI  - [Rapid morphogenesis of brain microvascular endothelial cells in culture system].
AB  - Endothelial cells of bovine brain microvascular vessels (BBECs), carotid artery
      (BCECs) and aorta (BAECs) were cultured on type I collagen and Matrigel. BBECs
      make tubular structures and BCECs and BAECs grow and make confluent monolayer on
      type I collagen gel. But BCECs and BAECs make tubular structures when second
      layer was overlaid. BBECs, BCECs and BAECs make tubular structures on Matrigel.
      These morphological changes were not affected by basic fibroblast growth factor.
      These results suggest that BBECs have more potent angiogenic ability than BCECs
      and BAECs.

PMID- 1378749
TI  - MR imaging of acute myocardial infarction in pigs using Gd-DTPA-labeled dextran.
AB  - Myocardial infarctions were induced in 12 pigs. In 6 pigs, dextran-(Gd-DTPA)15
      (approximately 0.1 mmol Gd/kg b.w.) was injected i.v. 4 to 4.5 hours after
      coronary artery occlusion. ECG gated MR images were obtained repeatedly before (n
      = 4) and after (n = 6) contrast medium injection. Relaxation times in blood
      samples were measured repeatedly. The animals were sacrificed 2 hours after
      contrast medium administration. The hearts were excised, reexamined in the MR
      equipment and stained with triphenyltetrazolium chloride (TTC) in order to define
      areas of infarction. The remaining 6 pigs were sacrificed 6 hours after occlusion
      without administration of contrast medium. These hearts were only imaged ex vivo.
      In vivo, the infarctions could not be identified with or without dextran-(Gd
      DTPA)15. Ex vivo, without contrast medium, the infarctions had an increased
      signal intensity, most pronounced in the T2-weighted images. Dextran-(Gd-DTPA)15
      caused a prolonged, pronounced shortening of T1 and T2 in blood samples. The
      infarct demarcation improved in the T1-weighted images after injection of dextran
      (Gd-DTPA)15, due to a moderate enhancement in normal myocardium and a stronger
      enhancement at the periphery of the infarctions, while the central parts of the
      infarctions were only weakly enhanced.

PMID- 1378750
TI  - Level of plasma prekallikrein and its inhibitors in reactors and nonreactors
      during intravenous enhancement with contrast media.
AB  - Complex contact activation systems may play a major role in the side effects of
      i.v. contrast media (CM). This is why quantitative measurements of several
      factors (plasma prekallikrein, hematocrit (hct), alpha-2-macroglobulin, alpha-1
      antitrypsin, and C1-esterase inhibitor) were determined prior to and following
      the injection of CM during body CT examination in 5 patient groups, each (n = 10)
      receiving one of 5 different CM, including ioxaglate, meglumine iodamide,
      metrizamide, iohexol, and meglumine diatrizoate. The initial plasma prekallikrein
      level was available from 45 patients and was statistically lower in reactors
      (mean 90.6 mumol TAMe/ml/h; n = 13) than in nonreactors (mean 107 mumol
      TAMe/ml/h; n = 32) (p = 0.006), but there was no statistically significant
      difference in the decrease of plasma prekallikrein before and at 5 min after the
      injection for those 2 groups. The initial plasma C1-esterase inhibitor level was
      lower in reactors, while the plasma alpha-2-macroglobulin level was higher in
      that group than in nonreactors. The results indicate that the measurement of
      plasma prekallikrein combined with plasma C1-esterase inhibitor and alpha-2
      macroglobulin measurement could be useful when predicting which patients are
      prone to CM reactions.

PMID- 1378751
TI  - Palliative care [continuing education credit].
AB  - Care of the dying patient provides one of the most challenging areas of nursing
      practice. An understanding of the skills, principles and range of palliative care
      can enable practitioners to maximise the quality of life of those with advanced
      cancer and other progressive illnesses.

PMID- 1378752
TI  - Tumor necrosis factor regulates tyrosine phosphorylation on epidermal growth
      factor receptors in A431 carcinoma cells: evidence for a distinct mechanism.
AB  - Previous studies of tumor necrosis factor (TNF) action on tumor cells revealed a
      possible role for tyrosine phosphorylation of epidermal growth factor (EGF)
      receptor in the growth-regulatory activities of this cytokine (N. J. Donato, G.
      E. Gallick, P. A. Steck, and M. G. Rosenblum, J. Biol. Chem., 264: 20474-20481,
      1989). EGF receptor immunoprecipitated from [32P] phosphate-equilibrated A431
      cells demonstrated that TNF treatment resulted in both a time- and concentration
      dependent stimulation of EGF receptor phosphorylation, which was maximal
      (approximately 3-fold) after 10-20 min of TNF exposure (10 nM). Incubation of
      A431 cells with an equivalent concentration of EGF resulted in similar
      stimulation of EGF receptor phosphorylation, albeit at different phosphotyrosine
      levels. Antiphosphotyrosine immunoblot analysis confirmed these results but
      suggested that the extent and kinetics of TNF-induced tyrosine phosphorylation
      were distinct from those obtained in EGF-treated cells. Resolution of tryptic
      phosphopeptides from EGF receptor demonstrated that TNF-induced phosphorylation
      of EGF receptor was similar, but not identical, to profiles obtained from EGF
      treated cells and distinct when compared to the actions of phorbol ester. Unlike
      EGF, TNF was unable to directly stimulate EGF receptor tyrosine kinase activity
      in membranes prepared from A431 cells. In addition, TNF treatment had no
      significant effect on either the high- or low-affinity ligand-binding sites on
      EGF receptor and did not alter the kinetics or extent of ligand-induced
      internalization of EGF receptors. However, EGF receptor biosynthesis was
      consistently increased upon prolonged treatment with TNF (4-12 h). Our results
      suggest that TNF regulates both phosphorylation and biosynthesis of EGF receptor
      in a manner distinct from that of both EGF and phorbol ester, and studies of the
      differential phosphorylation of EGF receptor may aid in understanding the
      molecular mode of TNF action.

PMID- 1378753
TI  - Expression of the PAX2 gene in human fetal kidney and Wilms' tumor.
AB  - We have examined the pattern of expression of the human PAX2 gene in Wilms'
      tumors and human fetal kidney by Northern blot and in situ hybridization. Human
      PAX2 encodes a paired box-containing protein and has a high degree of homology
      with mouse and Drosophila paired box genes. In situ hybridization analysis
      reveals that PAX2 is expressed in nephrogenic structures in fetal kidney and also
      in Wilms' tumors. This pattern of expression suggests that PAX2 may have a role
      in differentiation of tissues in the kidney. In fetal kidney, PAX2 expression
      rapidly attenuates following the initial differentiation, but no evidence of
      attenuation was found in Wilms' tumors. The timing of PAX2 expression is
      restricted to fetal development, although high levels of expression were also
      observed in nephrogenic rests of residual normal juvenile kidney tissue adjacent
      to a Wilms' tumor. Nephrogenic rests are the presumptive precursors of Wilms'
      tumor but are not necessarily neoplastic. The failure of PAX2 expression to
      attenuate in Wilms' tumors and nephrogenic rests may be associated with events
      leading to the onset of Wilms' tumor. By somatic cell hybrid mapping, the PAX2
      gene was localized to chromosome 10q22.1-q24.3, although this region has not
      previously been implicated in Wilms' tumor.

PMID- 1378754
TI  - Topographic organization, number, and laminar distribution of callosal cells
      connecting visual cortical areas 17 and 18 of normally pigmented and Siamese
      cats.
AB  - The callosal connections between visual cortical areas 17 and 18 in adult
      normally pigmented and "Boston" Siamese cats were studied using degeneration
      methods, and by transport of WGA-HRP combined with electrophysiological mapping.
      In normal cats, over 90% of callosal neurons were located in the supragranular
      layers. The supragranular callosal cell zone spanned the area 17/18 border and
      extended, on average, some 2-3 mm into both areas to occupy a territory which was
      roughly co-extensive with the distribution of callosal terminations in these
      areas. The region of the visual field adjoining the vertical meridian that was
      represented by neurons in the supragranular callosal cell zone was shown to
      increase systematically with decreasing visual elevation. Thus, close to the area
      centralis, receptive-field centers recorded from within this zone extended only
      up to 5 deg into the contralateral hemifield but at elevations of -10 deg and -40
      deg they extended as far as 8 deg and 14 deg, respectively, into this hemifield.
      This suggests an element of visual non-correspondence in the callosal pathway
      between these cortical areas, which may be an essential substrate for "coarse"
      stereopsis at the visual midline. In the Siamese cats, the callosal cell and
      termination zones in areas 17 and 18 were expanded in width compared to the
      normal animals, but the major components were less robust. The area 17/18 border
      was often devoid of callosal axons and, in particular, the number of
      supragranular layer neurons participating in the pathway were drastically
      reduced, to only about 25% of those found in the normally pigmented adults. The
      callosal zones contained representations of the contralateral and ipsilateral
      hemifields that were roughly mirror-symmetric about the vertical meridian, and
      both hemifield representations increased with decreasing visual elevation. The
      extent and severity of the anomalies observed were similar across individual
      cats, regardless of whether a strabismus was also present. The callosal pathway
      between these visual cortical areas in the Siamese cat has been considered
      "silent," since nearly all neurons within its territory are activated only by the
      contralateral eye. The paucity of supragranular pyramidal neurons involved in the
      pathway may explain this silence.

PMID- 1378755
TI  - Ability of different chemically modified heparins to potentiate the biological
      activity of heparin-binding growth factor 1: lack of correlation with growth
      factor binding.
AB  - A range of chemically modified heparins was examined for their ability to bind
      heparin-binding growth factor 1 (HBGF-1; acidic fibroblast growth factor) and
      potentiate the in vitro mitogenic and neurotrophic activity of HBGF-1. It was
      found that carboxyl-reduced heparin bound HBGF-1 as effectively as the native
      heparin molecule. Totally desulfated heparin and N-desulfated heparin lack HBGF-1
      binding capacity, and substitution of the exposed amino group with acetyl or
      acetoacetyl groups only partially restored binding capacity, indicating that N
      sulfates only play a limited role in growth factor binding. However, the failure
      of totally desulfated, N-resulfated heparin to interact with HBGF-1 demonstrated
      that N-sulfates alone are insufficient and ester sulfates are absolutely
      essential for HBGF-1 binding. In contrast, the ability of the modified heparins
      to potentiate the mitogenic activity of HBGF-1 correlated only to a limited
      extent with their affinity for HBGF-1. Thus, the carboxyl-reduced molecule which
      displayed similar affinity for HBGF-1 as native heparin was consistently less
      potent in augmenting mitogenesis. Similarly, the N-acetylated and the N
      acetoacetylated species, which had much lower affinity for HBGF-1 than the
      carboxyl-reduced molecule, conferred similar biological activity to HBGF-1
      whereas N-desulfated heparin, which was unable to bind growth factor, potentiated
      the mitogenic activity of HBGF-1 for both 3T3 and HUVE cells. In contrast, the
      neurotrophic activity of HBGF-1 was potentiated by modified heparin species which
      failed to bind HBGF-1 and were without activity in the mitogenic assays.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1378756
TI  - Structural characterization of x2 glycosphingolipid, its extended form, and its
      sialosyl derivatives: accumulation associated with the rare blood group p
      phenotype.
AB  - It has been suggested that the x2 glycosphingolipid (GSL) could offer a
      structural basis for a P-like antigen activity found in blood group p individuals
      [Kannagi R., Fukuda, M.N., Hakomori, S. (1982) J. Biol. Chem. 257, 4438]. The
      structures of the x2 and sialosyl-x2 GSLs have been confirmed unequivocally as
      shown below by +FAB-MS, methylation analysis by GC-MS, and 1H-NMR. We have
      established a [formula: see text] monoclonal antibody (TH2) specific for the
      GalNAc beta 1----3Gal beta 1----4GlcNAc epitope, the terminal trisaccharide of x2
      GSL. Application of MAb TH2 on TLC immunoblotting together with chemical analysis
      indicates the following points of interest: (i) the existence of extended type
      GSLs having the same x2 terminal structure; (ii) the chemical quantities of x2,
      sialosyl-x2, and extended x2 found in blood cells and in various tissues
      including carcinomas being nearly the same; (iii) considerably larger quantities
      of x2 and x2-derived structures found in blood samples of rare blood group p
      individuals. The accumulation of x2 and its derivatives in blood cells of p
      individuals is in contrast to the occurrence of these GSLs as extreme minor
      components in normal human red blood cells and tissues, and they may be
      responsible for the reported P-like activity in blood group p individuals [Naiki,
      M., & Marcus, D. M. (1977) J. Immunol. 119, 537].

PMID- 1378757
TI  - Fluorescence studies of the secondary structure and orientation of a model ion
      channel peptide in phospholipid vesicles.
AB  - A 21-residue peptide of the sequence (LSSLLSL)3 forms ion channels when
      incorporated into planar lipid bilayer membranes of
      diphytanoylphosphatidylcholine (diPhy-PC). The frequency of channel openings
      increases with the applied voltage gradient. We investigated the molecular and
      structural mechanisms underlying this voltage dependence. A series of seven
      peptides, each containing a tryptophan substituted for a single residue in the
      middle heptad, was synthesized, purified, and incorporated into small,
      unilamellar, diPhy-PC vesicles. We measured circular dichroism, maximum
      fluorescence emission wave-lengths, and fluorescence quenching by both aqueous
      and lipid hydrocarbon-associated quenchers. Circular dichroism spectra and the
      observed sequence periodicity of all fluorescence and fluorescence quenching data
      are consistent with an alpha-helical peptide secondary structure. Energy transfer
      quenching measurements using N-terminally labeled (LSSLLSL)3 co-incorporated at
      lipid/peptide ratios greater than 100 into vesicles with one of the Trp
      substituted peptides showed that the vesicle-associated peptide, in the absence
      of a voltage gradient across the bilayer, exists as an equilibrium mixture of
      monomers and dimers. Static fluorescence quenching measurements using different
      lipid-bound quenchers indicate that the helical axis of a representative lipid
      associated peptide is, on average, oriented parallel to the surface of the
      membrane and located a few angstroms below the polar head group/hydrocarbon
      boundary. This surface orientation for the peptide is confirmed by the
      complementary sequence periodicity observed for Trp fluorescence emission
      wavelength shifts and collisional quenching by aqueous CsCl.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1378758
TI  - Site-directed mutagenesis studies on subunit I of the aa3-type cytochrome c
      oxidase of Rhodobacter sphaeroides: a brief review of progress to date.

PMID- 1378759
TI  - The mitochondrial tRNA(Leu)(UUR)) mutation in MELAS: a model for pathogenesis.
AB  - The A----G transition at nucleotide 3243 of the mitochondrial tRNA(Leu)(UUR))
      gene has been associated with MELAS, a maternally-inherited mitochondrial
      disorder. We recently transferred mitochondria harboring this mtDNA mutation into
      a human cell line devoid of endogenous mtDNA (rho degrees cells), and showed: (1)
      decreased rate of synthesis and of steady-state levels of mitochondrial
      translational products, (2) reduced respiratory chain function and (3) increased
      amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from
      transcription of the 16S rRNA + tRNA(Leu)(UUR) + ND 1 genes. Because RNA 19
      contains rRNA sequences, we propose that this molecule is incorporated into
      mitochondrial ribosomes, and interferes disproportionately with mitochondrial
      translation, thereby causing the phenotypic changes associated with MELAS.

PMID- 1378760
TI  - In vivo properties of colicin A: channel activity and translocation across the
      envelope of Escherichia coli.

PMID- 1378761
TI  - CFTR, a channel with the structure of a transporter.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) belongs to a
      superfamily of active transport molecules. However, when expressed in a wide
      variety of heterologous cell systems and when purified to homogeneity and
      reconstituted in planar lipid bilayers, it exhibits low conductance chloride
      channel activity. We postulate that the active transport capability of the
      molecule has been adapted to provide very stringent metabolic control of this
      channel which is responsible for chloride secretion and hydration of wet
      epithelial surfaces.

PMID- 1378762
TI  - [Therapy of hemorrhagic shock using small volumes of hypertonic-hyperoncotic NaCl
      dextran solution--effects on the brain].
AB  - Infusion of small volumes of hypertonic/hyperoncotic solution (HHL: 7.2% NaCl/10%
      dextran 60) is highly effective in haemorrhagic shock. Cardiovascular function is
      restored in a matter of minutes by rapid mobilisation of extravasal fluid.
      However, little experience has been collected to date on the side effects on the
      brain by this new form of shock therapy. The present studies on HHL were
      conducted with particular reference to cerebral blood flow, cerebral oxygen
      supply, and intracranial pressure. Haemorrhagic shock with a drop in arterial
      blood pressure to 40 mmHg over a period of 30 min was induced in rabbits under
      alpha-chloralose anaesthesia by means of bloodletting. Subsequently, the
      hypertonic/hyperoncotic solution (HHL) was infused into the experimental animals
      within two minutes. The regional cerebral blood flow (H2-clearance) and the
      cerebral O2 supply were studied by determining the pO2 of the cerebral cortex in
      experimental animals without haemorrhagic shock but with infusion of HHL.
      Finally, separate single tests were conducted to analyse the effect of the
      infusion of HHL on the intracranial pressure after induction of a focal cold
      lesion of the brain in combination with the implantation of a rubber balloon in
      the epidural space as an intracranial space-occupying growth. Infusion of HHL
      during shock produced rapid normalisation of cardiac output, whereas in
      normovolaemic animals without shock it produced a temporary increase of this
      parameter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378763
TI  - Induction of IL-1: independent production of IL-1 alpha and IL-1 beta.
AB  - Lipopolysaccharide (LPS) either in its soluble form or associated with
      multilamellar phospholipid vesicles (liposomes) was investigated for its ability
      to induce human monocyte interleukin (IL)-1 alpha and IL-1 beta. When human
      monocytes were activated in vitro by LPS either in its soluble form or presented
      at the surface of lyophilized multilamellar vesicles (Lyo-MLV-LPS), both IL-1
      alpha and IL-1 beta were detected intracellularly and extracellularly, using
      specific antisera. In correlation with these findings, the mRNAs for IL-1 alpha
      and IL-1 beta were both found by Northern blot analysis. However, when human
      monocytes were stimulated by LPS incorporated into multilamellar vesicles which
      had not been previously lyophilized, a different pattern of IL-1 protein and
      message was observed. IL-1 alpha activity was detected only intracellularly and
      not in the supernatant, while IL-1 beta was not produced at all. Northern
      blotting revealed only mRNA for IL-1 alpha as soon as 0.5 h after stimulation and
      none for IL-1 beta. These data indicate independent induction of IL-1 alpha and
      IL-1 beta. Moreover, it appears that the regulation occurs at the transcriptional
      level, since with MLV-LPS only the mRNA for IL-1 alpha was induced. The lack of
      IL-1 beta could be due to either a blockage at the DNA level, an undetectable
      level of IL-1 beta mRNA, or a very short halflife for IL-1 beta mRNA. These
      findings indicate that although IL-1 alpha and IL-1 beta may have identical
      biological properties and share the same receptor, their induction and secretion
      are regulated by independent pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378764
TI  - Cyclosporin A and FK506 prevent the derepression of the IL-2 gene in mitogen
      induced primary T lymphocytes.
AB  - In resting primary T lymphocytes the interleukin 2 (IL-2) gene is silenced by a
      repressor binding to the Pud element spanning positions -292 to -264 upstream of
      the cap site. Upon T-cell activation, this silencer is displaced by a positive
      transcription factor (TF) and the gene is derepressed and transcribed.
      Cyclosporin A (CsA) and FK506 interfere with normal derepression of the IL-2
      gene. Both drugs exert no direct effect on basal transcription of the IL-2 or
      control viral genes. Direct addition does not abolish the active state of
      positive TFs present in proteins from activated T cells. However, if T cells are
      activated in the presence of either drug, their proteins not only fail to
      derepress, but efficiently and irreversibly silence IL-2 transcription. DNA
      protein binding data show that proteins present in drug-treated cells form
      retarded complexes corresponding in size to the silencer and positive TF. Thus,
      in drug-treated cells a functional silencer persists, and a positive TF-like
      factor appears which is functionally abnormal. Moreover, drug-treated T cells
      appear to form a component that prevents functioning of normal positive TF.

PMID- 1378765
TI  - Expression of recombinant human anti-MAG antibodies in non-lymphoid mammalian
      cells.
AB  - The variable heavy and light chain genes of a monoclonal, IgM, anti-MAG antibody
      from a patient with neuropathy were inserted into expression vectors containing
      the gamma and kappa constant regions respectively and co-transfected into monkey
      kidney CV1P cells. The expressed antibody had the same antigenic specificity but
      significantly lower avidity than the native IgM, anti-MAG, antibody as detected
      by ELISA. When the variable heavy chain gene of the anti-MAG antibody was co
      transfected with the variable light chain gene from another monoclonal, IgM, anti
      MAG antibody, a fully assembled antibody was expressed as determined by a
      trapping ELISA, but it did not bind to (MAG) or to sulfated glucuronic acid
      paragloboside, indicating that both heavy and light chains contribute to the
      binding activity.

PMID- 1378766
TI  - Parkinson's disease and dementia: clinical and neurochemical correlations.
AB  - In 38 old aged parkinsonian patients, two major subgroups could be established:
      one with predominant akinesia, rigidity, postural instability and accompanying
      cognitive impairment with intellectual deterioration correlated with duration of
      disease but not with age of onset and another with predominant tremor and
      relatively intact intellectual functions. The mean somatostatin-like
      immunoreactivity (SLI) level in the cerebrospinal fluid (CSF) was significantly
      lower in parkinsonian patients (21.4 +/- 8.1 fmol ml-1) compared to senile
      control patients (29.5 +/- 9.4 fmol ml-1). In contrast to senile dementia of
      Alzheimer's type SLI was not correlated with dementia scores but with motor
      disease progression. Homovanillic acid (HVA) significantly decreased only in
      patients without L-DOPA treatment. Correlations between SLI, HVA and 5
      hydroxyindole acetic acid (5-HIAA) indicate a degeneration of multiple neuronal
      networks which includes somatostatinergic neurons.

PMID- 1378767
TI  - Fibroblast growth factor injected in cerebral ventricles does not decrease mean
      arterial blood pressure.
AB  - Intracerebroventricular injections of acidic fibroblast growth factor (aFGF) in
      rats did not elicit any change in the mean arterial blood pressure, and also did
      not appreciably affect the hypotensive effect of intravenous injections of aFGF.
      These observations are of general clinical interest, since such effects could
      constitute important drawbacks for the therapeutic applications of FGF.

PMID- 1378768
TI  - Laminar distribution of neurons projecting from area V1 to V2 in macaque and
      squirrel monkeys.
AB  - The present study reevaluates the sublaminar distribution and cellular morphology
      of neurons projecting from area V1 to V2. Observations are based on retrogradely
      transported HRP, Phaseolus vulgaris leucoagglutinin (PHA-L), or biocytin after
      injections made in area V2 of three squirrel monkeys and eight macaques. With
      material prepared in the coronal or horizontal tissue planes, it is clear that
      projection neurons in V1, in both species, are concentrated in layer 4B and in a
      single band (150-250 microns wide) restricted to the upper subdivision of layer 3
      (layer 3A). There are also labeled neurons, but fewer in number, in layers 3B and
      4A, and occasionally in layers 2 and 5. Golgi-like labeling from PHA-L or
      biocytin confirmed that most of the projection neurons in layer 3A are pyramidal.
      As reported for several other corticocortical systems, these pyramidal neurons
      differ in soma size, soma shape, and dendritic geometry. These results emphasize
      the complex organization of layer 3, and the distributed nature of efferent
      projections from area V1. Given the selective connectivity of vertical
      interlaminar networks, these results specifically suggest that information
      transmitted to area V2 from neurons in layer 3A reflects more highly processed,
      convergent input than that originating from either layer 3B or 4B.

PMID- 1378769
TI  - Bromovirus RNA replication and transcription.
AB  - Ongoing characterization of cis-acting sequences in bromovirus RNA-dependent RNA
      replication and transcription has been complemented in the past year by progress
      in elucidating the roles of virus-encoded replication factors 1a and 2a. Recent
      studies suggest that the helicase-like 1a and polymerase-like 2a proteins may
      participate in a well organized replication complex in which polymerase,
      helicase, and possibly capping functions operate in a highly coordinated manner.

PMID- 1378770
TI  - HPA-related CSF neuropeptides in suicide attempters.
AB  - Corticotropin-releasing hormone (CRH), somatostatin (SOM), delta-sleep-inducing
      peptide (DSIP), neuropeptide Y (NPY), beta-endorphin (beta-END), and vasopressin
      (AVP), which are regarded as being involved in the HPA-regulation were
      investigated in lumbar CSF of 44 suicide attempters. The patients were diagnosed
      according to the DSM-III-R, and rated with the MADRS. The neuropeptides were
      compared with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF
      and with post-dexamethasone plasma cortisol. We found strong correlations between
      CRH and the peptides SOM and beta-END. The latter also correlated positively with
      SOM. There were no differences between men and women. Patients with major
      depressive disorders had significantly lower SOM, CRH, and DSIP than other
      patients. Both SOM and beta-END correlated negatively with post dexamethasone
      plasma cortisol in all patients. We found no significant relationships between
      neuropeptides and CSF 5-HIAA. Patients who had made previous suicide attempts had
      significantly lower CRH than those who had not. No other significant associations
      between neuropeptides and suicidal subgroups of patients appeared, and there was
      no indication of specific neuropeptide patterns in patients who later completed
      suicide. Intercorrelations of some neuropeptides and low SOM and DSIP in major
      depressed patients are findings in line with those by others.

PMID- 1378771
TI  - Enlargement of the salivary gland after ritodrine treatment in pregnant women.

PMID- 1378772
TI  - An algorithm for comparing RNA secondary structures and searching for similar
      substructures.
AB  - To access the functional informations carried by RNA molecules at the level of
      their secondary structure interactions, we propose a comparison method based on a
      tree edit algorithm which takes into account the tree structure of RNA foldings.
      Any secondary structure is translated into a tree involving all its elementary
      substructures; then a shorter condensed tree is built in which any unbranched
      helix interspersed with bulges and interior loops is taken as a single node. This
      method includes several parameters: a comparison matrix between structural units,
      gap penalties, and the scoring between nodes of the condensed trees. Their
      effects have been analysed using as a model a rapidly divergent domain of the
      large ribosomal RNA, for which structural variation during evolution is well
      known. This method allows one to recognize precisely, in large target molecules,
      definite substructures that present with the query molecules only a limited set
      of closely related secondary structure features; it is still efficient if
      intervening features, which can correspond to insertion/deletion of entire stem
      regions, separate such structural elements. When coupled with a hierarchical
      clustering algorithm, this method is suitable for classifying RNA molecules
      according to their secondary structure homologies.

PMID- 1378773
TI  - A procedure for RNA pseudoknot prediction.
AB  - The RNA pseudoknot has been proposed as a significant structural motif in a wide
      range of biological processes of RNAs. A pseudoknot involves intramolecular
      pairing of bases in a hairpin loop with bases outside the stem of the loop to
      form a second stem and loop region. In this study, we propose a method for
      searching and predicting pseudoknots that are likely to have functional meaning.
      In our procedure, the orthodox hairpin structure involved in the pseudoknot is
      required to be both statistically significant and relatively stable to the others
      in the sequence. The bases outside the stem of the hairpin loop in the predicted
      pseudoknot are not entangled with any formation of a highly stable secondary
      structure in the sequence. Also, the predicted pseudoknot is significantly more
      stable than those that can be formed from a large set of scrambled sequences
      under the assumption that the energy contribution from a pseudoknot is
      proportional to the size of second loop region and planar energy contribution
      from second stem region. A number of functional pseudoknots that have been
      reported before can be identified and predicted from their sequences by our
      method.

PMID- 1378774
TI  - Natural sequence code representations for compression and rapid searching of
      human-genome style databases.
AB  - Numeric descriptions ('bio-informatic descriptions') of amino acid residues have
      been developed which will be of value whenever the quality and quantity of
      information in very large (i.e. 'human genome style') gene and protein sequences
      is to be compared or manipulated. These codes are as natural as possible by our
      criteria (the same principles could be used in revision of the criteria). In
      particular, in storing and searching large amounts of sequence data, natural
      codes--which relate to the properties of amino acids--can be combined with
      existing fast-search algorithms but introduce several advantages. The code can be
      assigned such that sub-selection of bits leads to compressed databases with
      residues defined less specifically, by classes of properties. The most compressed
      representation leads to the specification of a residue as polar or non-polar,
      while the most extended representation used at present also allows specification
      of, for example, glyco-asparagine and phosphoserine. Preliminary studies on both
      a supercomputer and smaller machines suggest a 'worst-case' speeding of
      approximately 4.5-fold. For more intelligent searching, coding extensions mixed
      with the basic sequence data give the sequence data some of the character of a
      computer program.

PMID- 1378775
TI  - Actin dynamics during the cell cycle in Chlamydomonas reinhardtii.
AB  - We have used two monoclonal antibodies to demonstrate the presence and
      localization of actin in interphase and mitotic vegetative cells of the green
      alga Chlamydomonas reinhardtii. Commercially available monoclonal antibodies
      raised against smooth muscle actin (Lessard: Cell Motil. Cytoskeleton 10:349-362,
      1988; Lin: Proc. Natl. Acad. Sci. USA 78:2335-2339, 1981) identify Chlamydomonas
      actin as a approximately 43,000-M(r) protein by Western immunoblot procedures. In
      an earlier study, Detmers and coworkers (Cell Motil. 5:415-430, 1985) first
      identified Chlamydomonas actin using NBD-phallacidin and an antibody raised
      against Dictyostelium actin; they demonstrated that F-actin is localized in the
      fertilization tubule of mating gametes. Here, we show by immunofluorescence that
      vegetative Chlamydomonas cells have an array of actin that surrounds the nucleus
      in interphase cells and undergoes dramatic reorganization during mitosis and
      cytokinesis. This includes the following: reorganization of actin to the anterior
      of the cell during preprophase; the formation of a cruciate actin band in
      prophase; reorganization to a single anterior actin band in metaphase;
      rearrangement forming a focus of actin anterior to the metaphase plate;
      reextension of the actin band in anaphase; presence of actin in the forming
      cleavage furrow during telophase and cytokinesis; and finally reestablishment of
      the interphase actin array. The studies presented here do not allow us to
      discriminate between G and F-actin. None the less, our observations,
      demonstrating dynamic reorganization of actin during the cell cycle, suggest a
      role for actin that may include the movement of basal bodies toward the spindle
      poles in mitosis and the formation of the cleavage furrow during cytokinesis.

PMID- 1378776
TI  - Physicochemical and biologic properties of interferons and their potential uses
      in drug delivery systems.
AB  - Interferons (IFNs) are a complex group of proteins and glycoproteins able to
      express antiviral, immunomodulatory, and differentiation activities. In
      physiological conditions, they are produced upon induction, in basal amounts, and
      in restricted microenvironments where they act in a paracrine fashion, hardly
      reaching the circulation and not affecting parenchymal cells. In some acute
      infections, production of IFN is diffused and, therefore, IFN levels become
      detectable in plasma, and side effects, such as the typical flu-like syndrome,
      ensue. A similar situation occurs during pharmacological therapy, particularly
      when IFN is administered through conventional routes (IV, IM, and SC). We have
      finally realized that IFNs are normally not circulatory proteins, and because
      they are unselective during therapeutic intervention, toxicity can overcome
      beneficial effects. For this reason, there is a pressing need to optimize
      treatment, dosages, and schedules for improving the therapeutic index. A further
      important issue is the definition of routes of IFN administration able to achieve
      the maximal activity where needed, and in fact, when IFNs are used as cytostatic
      drugs, regional therapy improves the treatment. However, when IFNs are used as
      immunomodulatory agents, other strategies must be sought, and the interaction of
      IFN with epithelial membranes and mucosal associated lymphoid tissue becomes
      important. Hence, delivery via oropharyngeal, intestinal, rectal,
      bronchioalveolar, and lymphatic routes appears useful probably because they
      simulate the physiological distribution and action of IFNs.

PMID- 1378777
TI  - Molecular basis for the association between HLA DR4 and rheumatoid arthritis.
      From the shared epitope hypothesis to a peptidic model of rheumatoid arthritis.
AB  - Susceptibility to rheumatoid arthritis (RA) maps to residues QKRAA/QRRAA in the
      third hypervariable region of the HLA DR beta 1 chain. Peptides from the same
      area of MHC class II molecules are able to modulate the T-cell repertoire by
      deleting self-reactive T-cells. The Epstein Barr virus glycoprotein gp110 and the
      dna J heat-shock protein from E. coli mimic the third hypervariable region of HLA
      Dw4DR beta 1. Thus, the same area of HLA DR beta 1 carries susceptibility to RA,
      modulates the T-cell repertoire and is mimicked by human pathogens. RA may
      originate from a particular shape imposed on the T-cell repertoire by the
      QKRAA/QRRAA sequence in the third hypervariable region of HLA DR beta 1.

PMID- 1378778
TI  - Severe pre- and postnatal growth retardation, developmental delay with hypotonia
      and marked hypotrophy of the distal extremities, dental anomalies, and eczematous
      skin. A new autosomal recessive entity.
AB  - We report on three young children, two girls and one boy, with pre- and postnatal
      growth deficiency, hypotonia, psychomotor retardation with notably impaired
      speech development, hypotrophy of the distal extremities, small hands and feet,
      small and widely spaced teeth, eczematous skin, and, in two of them, a partial
      agenesis of the corpus callosum. To our knowledge this specific combination of
      features has not been reported before. Since the two girls are sisters and the
      boy is the product of a consanguineous marriage, the inheritance of this new
      syndrome appears to be autosomal recessive.

PMID- 1378779
TI  - Epidemiology of HIV infection in women.

PMID- 1378780
TI  - Skin lesions due to okra (Hibiscus esculentus L.): proteolytic activity and
      allergenicity of okra.
AB  - The present report describes experimental studies on the proteolytic activity of
      the secretion on the surface of okra pods and the allergenicity of okra
      components, to clarify the etiology of skin lesions due to okra. Proteolytic
      activity was detected on the surface of immature okra pods and seemed to be
      sufficient to cause the skin lesions. Further, in vivo, intradermal injection of
      the enzyme solution prepared from immature okra pods led to increased capillary
      permeability in guinea pigs, in contrast to heated preparations. The fraction
      purified by preparative paper chromatography from an ethyl acetate extract of
      okra pods showed moderate allergenicity in the guinea pig maximization test. The
      present experimental evidence supports our suggestions from previous surveys that
      the proteolytic enzyme of okra may be responsible for development of skin
      lesions, and that allergic contact dermatitis may also play a part in addition to
      irritant contact dermatitis.

PMID- 1378781
TI  - Immunofluorescent labeling of centromeres for flow cytometric analysis.
AB  - A procedure to stain the centromeric region of chromosomes for dual beam flow
      cytometric analysis is described. Serum from a CREST (Scleroderma syndrome)
      patient presenting a high titer of anticentromeric antibodies was chosen on the
      basis of specificity of labeling of cells on slides. The high affinity of the
      antibodies to centromeres and low binding to chromosomal arms allowed the
      development of an indirect immunofluorescent labeling procedure using isolated
      and unfixed chromosomes stabilized by Mg++ ions. Discontinuous Ficoll gradients
      were used to separate chromosomes from unbound antibodies. With this procedure,
      chromosome clumping and degradation were minimal. The chromosomes were then
      stained with the DNA dyes Hoechst 33258 and chromomycin A3, before dual beam flow
      cytometric analysis. Flow karyotypes, with good chromosome peak resolution, were
      obtained for both human and hamster chromosomes subjected to the immunolabeling
      procedure. For quantification of FITC fluorescence due to bound antibody,
      chromosomes were counterstained with Hoechst only. The FITC intensity of antibody
      labeled human and hamster chromosomes were 4-10 and 20 times greater than control
      chromosomes, respectively. These results suggest that the staining procedure may
      be suitable for immunolabeling of chromosomes with antibodies recognizing other
      nuclear proteins and their subsequent quantification by flow cytometry.

PMID- 1378782
TI  - Therapeutic targets in ischaemic heart disease.
AB  - The adequate treatment of a disease syndrome is dependent upon a clear definition
      of the symptomatic, pathological, physiological and prognostic targets against
      which therapy is to be deployed. The syndromes of ischaemic heart disease,
      including angina pectoris, are complex in origin, pathology, pathophysiology and
      natural history, and a complete clinical profile is difficult, if not impossible,
      to achieve in individual patients. The prime goals of pharmacotherapy in
      ischaemic heart disease are easy to define, but difficult to accomplish in
      practice. Relief of pain, breathlessness and fatigue are the prime clinical
      targets for pharmacotherapy. In view of their sinister significance, the
      electrophysiological indications of myocardial ischaemia, whether symptomatic or
      silent, are also crucial targets towards which therapy must be directed.
      Ischaemic heart disease is accompanied by a wide variety of regional and global
      abnormalities of myocardial contractile function associated with widespread
      reflex stimulation of the peripheral vascular system and neuroendocrine systems.
      Primarily, drug therapy must be directed at correction of these
      pathophysiological components of the syndrome. Longer term but no less essential
      goals in the treatment of ischaemic heart disease are the prevention of the
      clinical sequelae of the syndrome and its progression. A natural sequel of
      coronary artery obstructive disease is successive thrombotic events and loss of
      myocardium. Calcium antagonists, by preventing the increase in myocardial
      cytosolic calcium during acute ischaemic episodes, defer cell necrosis; in this
      respect, they are unique among currently available antianginal drugs. With regard
      to progression, the prime pathological cause of ischaemic heart disease is
      coronary atheroma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378783
TI  - Calcium antagonists and silent myocardial ischaemia.
AB  - Silent myocardial ischaemia results from an imbalance between myocardial oxygen
      supply and demand. There is evidence in favour of both increased coronary
      vasomotor tone and increased oxygen demand as major independent causes of silent
      ischaemia. An ongoing study is assessing the efficacy of a slow release
      formulation of the calcium antagonist gallopamil in patients with stable angina
      pectoris. In a nonblind comparison with placebo in 13 patients, slow release
      gallopamil 100mg twice daily produced a marked reduction in exercise-induced
      myocardial ischaemia, and a moderate reduction in spontaneous ischaemia. The
      significance of these preliminary findings will emerge in the double-blind,
      placebo-controlled phase of the study. Studies using long term ECG monitoring to
      compare the anti-ischaemic efficacy of various calcium antagonists indicate that
      agents with negative inotropic actions suppress silent myocardial ischaemia to a
      greater extent than calcium antagonists such as nifedipine, which tend to
      increase heart rate. Also, beta-adrenoceptor blockers have produced excellent
      results in the treatment of myocardial ischaemia, despite their theoretical
      disadvantage of not reducing coronary vasomotor tone. The role of pharmacological
      therapy in the suppression of silent myocardial ischaemia will only be
      established when the drugs concerned have been adequately characterised with
      regard to their effect on prognosis, adverse effects and risk:benefit ratio.

PMID- 1378784
TI  - The molecular basis for the use of calcium antagonists in ischaemic heart
      disease.
AB  - Calcium antagonists are useful for the management of patients with ischaemic
      heart disease, particularly when used prophylactically. At the cellular level,
      these drugs act primarily by limiting calcium ion (Ca++) entry through the
      voltage-sensitive Ca(++)-selective channels, an effect that contributes markedly
      to their 'energy sparing' properties. However, the long term use of these drugs
      has additional advantages, particularly with respect to their ability to slow
      Ca(++)-dependent processes involved in the formation of atherogenic lesions,
      partially antagonise the effects of the raised levels of circulating endothelin-1
      encountered during ischaemia-induced heart failure and hypertension, and trap and
      immobilise oxyradicals. Prolonged episodes of ischaemia result in an irreversible
      loss of homeostasis with respect to Ca++. However, the increase in myocardial
      cytosolic Ca++ caused by relatively short periods of ischaemia is small,
      reversible, and markedly attenuated by the prophylactic use of calcium
      antagonists. In the isolated, perfused rat heart, verapamil pretreatment produces
      statistically significant inhibition of the increase in cytosolic Ca++ during 20
      minute global ischaemia. This stereospecific effect is associated with a decrease
      in the rise in total tissue Ca++ during reperfusion and amelioration of the
      adenosine triphosphate depletion caused by ischaemia. In general, discussion
      relating to the molecular basis of the use of calcium antagonists in the
      management of patients with ischaemic heart disease needs to take into account
      the duration of the ischaemic event, the workload on the myocardium, the need for
      prophylactic therapy, and the presence of exacerbating factors such as
      atherosclerosis and tobacco smoking. The early rise in cytosolic Ca++, the source
      of which remains uncertain, appears to be an important focus for anti-ischaemic
      drug therapy.

PMID- 1378785
TI  - Primary prevention potential of the calcium antagonists. Effects on blood
      pressure and lipid pattern.
AB  - Untreated hypertension has a variety of serious consequences, such as stroke,
      congestive heart failure and coronary heart disease, the incidences of which
      escalate sharply in the presence of other risk factors. Traditional
      antihypertensive therapy has been associated with reductions in the frequency of
      strokes, congestive heart failure and kidney failure, but a corresponding decline
      in myocardial infarctions has not been observed. Deleterious changes in lipid
      metabolism that are induced by these agents may counteract the beneficial effects
      of blood pressure reduction. Calcium antagonists have been used successfully in
      the management of hypertension for more than a decade. To define the impact of
      the calcium antagonist verapamil on metabolic parameters, 45 hypertensive
      patients were treated with verapamil monotherapy and followed up for 4 to 8
      years. After a mean treatment period of 5.3 years, total cholesterol and
      triglycerides were unchanged, whereas mean high density lipoprotein (HDL)
      cholesterol increased significantly, from 1.17 +/- 0.41 to 1.39 +/- 0.36 mmol/L
      (p less than 0.05). Other important biochemical parameters were unaffected by
      verapamil therapy. The primary target organs of hypertension are the arterial
      system and the myocardium. Accumulating literature now suggests that the calcium
      antagonists may represent an effective therapeutic approach to hypertension that
      controls both the pressure-related and atherosclerotic complications.

PMID- 1378786
TI  - The importance of stress-induced cardiac wall motion abnormalities in the
      evaluation of drug intervention.
AB  - Stress-induced wall motion abnormalities are a sensitive marker of myocardial
      ischaemia. Stress echocardiography has recently been the subject of increasing
      interest because of its improved feasibility and compatibility with new and
      effective alternative stresses. Transoesophageal atrial pacing (TAP) with 2
      dimensional echocardiography (2-D echo) is a recently developed echo
      cardiographic stress procedure that has been shown to be reliable and effective
      in both the diagnosis and evaluation of stress-induced myocardial ischaemia. TAP
      with 2-D echo was performed after treatment with placebo and intravenous
      gallopamil 0.03 mg/kg in 12 patients with stable, reproducible angina of effort.
      Compared with placebo, gallopamil treatment increased the time to 1 mm ST-segment
      depression (6.6 vs 5.3 minutes; p less than 0.05) and improved the ventricular
      wall motion score at a heart rate of 130 beats/min (17 vs 15; p less than 0.01)
      and 150 beats/min (13 vs 11; p = 0.07). Three patients who developed angina after
      placebo administration were symptom-free after gallopamil. Thus, gallopamil
      exerts a beneficial effect on atrial pacing-induced ischaemia, by increasing the
      pacing time to the ischaemic threshold and reducing the extent of dysfunctional
      myocardium during ischaemia.

PMID- 1378787
TI  - Secondary and tertiary prevention with calcium antagonists in coronary artery
      disease.
AB  - Recent multicentre studies evaluating the therapeutic value of calcium
      antagonists in reducing the incidence of cardiovascular complications after
      myocardial infarction (secondary prevention) and in retarding the development of
      atherosclerosis in coronary artery disease (tertiary protection) are reviewed.
      The prognosis of patients after acute myocardial infarction can be improved not
      only by interventional measures such as aortocoronary bypass surgery or
      percutaneous transluminal catheter angioplasty, but also by various drugs.
      Numerous studies have shown that beta-blockers and platelet aggregation
      inhibitors can reduce mortality and reinfarction rates. Calcium antagonists in
      secondary prevention trials after acute myocardial infarction, however, have
      produced variable results. Whereas the Secondary Prevention Reinfarction Israeli
      Nifedipine Trial (SPRINT) [Israeli SPRINT Study Group 1988] with nifedipine
      showed no beneficial effect of the drug, studies with verapamil in the Danish
      Verapamil Infarction Trial II (DAVIT II) [Danish Study Group on Verapamil in
      Myocardial Infarction 1990] and diltiazem in the Multicentre Diltiazem
      Postinfarction Trial (MDPIT) [Multicenter Diltiazem Postinfarction Trial Research
      Group 1988] as secondary prevention have demonstrated improvements in survival
      and cardiovascular complications, but these improvements were restricted to
      patients without heart failure. In view of the ability of calcium antagonists to
      reduce atheroma progression in coronary artery disease in animal models, the
      antiatherosclerotic effects of these agents in clinical studies have generally
      been disappointing. In the International Nifedipine Trial on Antiatherosclerotic
      Therapy (INTACT) [Lichtlen et al. 1990], however, nifedipine treatment was
      associated with a 28% reduction in new lesion development, but did not affect the
      development of severe lesions. Similar results have been obtained with
      nicardipine.

PMID- 1378788
TI  - Management of angina pectoris. Modern concepts.
AB  - While William Heberden gave us an excellent clinical description of angina
      pectoris more than 200 years ago, the understanding and management of this
      disorder have undergone major development since then, and especially so in recent
      years. The pathological basis for the disease was established shortly after
      Heberden's account. The concept of the imbalance between supply and demand was
      postulated in the nineteenth century. Recent progress has been made in mainly
      three areas: the better definition of prognosis, new insights into
      pathophysiology, and newer management modalities and aims. Today, the combination
      of the patient's functional state (exercise test), his heart (ventricular
      function) and coronary anatomy (angiography) enables us to accurately define the
      prognosis of the disease. Sophisticated studies have now demonstrated that during
      an exercise-induced angina attack there is a reduction in coronary blood flow and
      an increase in coronary resistance. Mechanisms associated with the angina attack
      involve the sclerotic epicardial arteries and the microcirculation. Further major
      advances in the medical management of angina pectoris now depend on our ability
      to improve prognosis and retard the development of the atherosclerotic process.

PMID- 1378789
TI  - Nitric oxide mediates the vascular actions of cytokines in septic shock.

PMID- 1378790
TI  - Characterization of the yeast BMH1 gene encoding a putative protein homologous to
      mammalian protein kinase II activators and protein kinase C inhibitors.
AB  - We describe the identification and characterization of the BMH1 gene from the
      yeast Saccharomyces cerevisiae. The gene encodes a putative protein of 292 amino
      acids which is more than 50% identical with the bovine brain 14-3-3 protein and
      proteins isolated from sheep brain which are strong inhibitors of protein kinase
      C. Disruption mutants and strains with the BMH1 gene on multicopy plasmids have
      impaired growth on minimal medium with glucose as carbon source, i.e. a 30-50%
      increase in generation time. These observations suggest a regulatory function of
      the bmh1 protein. In contrast to strains with an intact or a disrupted BMH1 gene,
      strains with the BMH1 gene on multicopy plasmids hardly grew on media with
      acetate or glycerol as carbon source.

PMID- 1378791
TI  - Fidelity of the reverse transcriptase of human immunodeficiency virus type 2.
AB  - The relatively low fidelity of human immunodeficiency virus type 1 reverse
      transcriptase (HIV-1 RT) was implicated as a major factor that contributes to the
      genetic variability of the virus. Extension of mismatched 3' termini of the
      primer DNA was shown to be a major determinant of the infidelity of HIV-1 RT.
      Human immunodeficiency virus type 2 (HIV-2) also shows extensive genetic
      variations. Therefore, we have analyzed the fidelity of the DNA-dependent DNA
      polymerase activity of HIV-2 RT and compared it with those of RTs of HIV-1 and
      murine leukemia virus (MLV). Like other retroviral RTs, the HIV-2 RT was shown to
      lack a 3'----5' exonuclease activity. The ability of HIV-2 RT to extend preformed
      3'-terminal A:A, A:C and A:G mispairs was examined by quantitating the amount and
      length of extended primers. The results demonstrate a relatively efficient
      mispair extension by HIV-2 RT with a specificity of A:C much greater than A:A
      greater than A:G. The mispair extension appears to be affected mainly by the
      increase of apparent Km values rather than by the change in Vmax values. The
      relative extension frequencies from all mispairs with HIV-1 and HIV-2 RTs was 6-
      to 9-fold greater than that of MLV RT, suggesting that the HIV enzymes are
      substantially more error-prone than MLV RT.

PMID- 1378792
TI  - Preparation of a stable subunit of Japanese elderberry (Sambucus sieboldiana)
      bark lectin and its application for the study of cell surface carbohydrates by
      flow cytometry.
AB  - A stable subunit of Sambucus sieboldiana bark lectin (MSSA) was prepared by
      selective reduction of disulfide bridges between the subunits and alkylation with
      4-vinylpyridine. Amino acid analysis of MSSA revealed that 1.4 cysteine residues
      per subunit were selectively modified. MSSA failed to agglutinate rabbit
      erythrocytes and precipitate fetuin. However, MSSA retained the ability to bind
      to fetuin, as detected by ELISA. Neu5Ac alpha 2-6lactose inhibited the binding to
      fetuin of both SSA and MSSA. Flow cytometric analysis showed that human
      histocytic lymphoma U937 cells were clearly stained with FITC-labeled MSSA (FITC
      MSSA) without any detectable agglutination and that this staining was almost
      completely inhibited by the addition of Neu5Ac alpha 2-6lactose (2 mM). Treatment
      of U937 cells with native FITC-SSA at the sub-agglutinating concentration (0.3
      microgram/ml) showed much poorer fluorescence intensity than that of MSSA,
      suggesting that MSSA is an invaluable tool for the detection of cell surface
      glycoconjugates containing NeuAc alpha 2-6Gal/GalNAc sequences by flow cytometry.

PMID- 1378793
TI  - 3'-Mercapto-2',3'-dideoxynucleotides are high effective terminators of DNA
      synthesis catalyzed by HIV reverse transcriptase.
AB  - Four 3'-mercapto-2',3'-dideoxynucleoside 5'-triphosphates (A, G, C and T) were
      tested as DNA chain terminator substrates for calf thymus alpha-DNA polymerase,
      E. coli DNA polymerase I Klenow fragment, terminal deoxynucleotidyl transferase
      and reverse transcriptases of AMV, HIV and MLV viruses. It was shown that the
      analogues selectively and irreversibly terminated DNA chain elongation by AMV and
      HIV reverse transcriptases and the terminal transferase. Other DNA polymerases
      tested did not use the nucleotide analogues as chain terminator substrate.

PMID- 1378794
TI  - Determination of sex ratio of spermatozoa with a deoxyribonucleic acid-probe and
      quinacrine staining: a comparison.
AB  - OBJECTIVE: To evaluate sex selection of spermatozoa. DESIGN: A deoxyribonucleic
      acid (DNA) probe (pDP34) detecting distinguishable loci on both X and Y
      chromosome was used to validate the quinacrine-staining method that is often used
      for determination of the percentage of Y-bearing sperm. Sperm samples were
      centrifuged over Percoll to obtain samples with a high X:Y ratio according to the
      quinacrine-staining method. Controls (sperms before processing over Percoll) and
      processed sperms were subjected to DNA extraction and analysis with the DNA
      probe. RESULTS: The DNA analysis revealed a 1.0 X:Y ratio of the spermatozoa
      before and after Percoll separation. CONCLUSION: We conclude that the quinacrine
      method is not suitable for evaluation of methods that claim to separate X and Y
      bearing sperm.

PMID- 1378795
TI  - CD45; from alloantigen to mapping of restricted epitopes using recombinant
      soluble CD45 isoforms.

PMID- 1378796
TI  - Immunological techniques in biotechnology research.

PMID- 1378797
TI  - Peptide antigens.

PMID- 1378798
TI  - Protein engineering of amylases.

PMID- 1378799
TI  - Isolation of rat urinary alpha 2-euglobulin: a comparison of exhaustive dialysis
      versus Centriprep ultrafiltration.

PMID- 1378800
TI  - Involvement of cyclic adenosine monophosphate in the stimulation of gonadotropin
      secretion from the pituitary of the teleost fish, tilapia.
AB  - The present study examines the involvement of cAMP in the transduction of the
      short-term effect of gonadotropin-releasing hormone (GnRH) on gonadotropin
      release in the teleost fish, tilapia. A 5 min pulse of dibutyryl cyclic AMP
      (dbcAMP; 0.03-3 mM) or forskolin (0.1-10 microM) resulted in dose-dependent
      surges in tilapia gonadotropin (taGTH) secretion from the perifused pituitary.
      The initial increase in taGTH in response to dbcAMP (3 mM) occurred within 6 min.
      The concentration of cAMP in the effluent medium increased about 20-fold after a
      pulse of [D-Ala6,Pro9-NEt]-luteinizing hormone-releasing hormone (LHRH) (GnRHa;
      100 nM). To rule out the possibility that the observed effects were due to
      stimulation by endogenous GnRH release from intact nerve terminals present in the
      fragments, further experiments were performed in primary cultures of dispersed
      pituitary cells. Exposure (30 min) of the cells to forskolin (0.01-1.0 microM)
      resulted in a dose-dependent increase in taGTH release similar to that achieved
      by GnRHa (1 pM to 10 nM). Also 8-bromo cAMP (0.01-1.0 mM) evoked a dose-related
      increase in taGTH release. A 3-fold increase in the release occurred in the
      presence of isobutylmethylxanthine (IBMX) (0.2 mM), similar to that obtained by
      GnRHa (1.0 nM) in the absence of IBMX. However, when combined, the increase in
      taGTH release was 16-fold. Moreover, exposure of the cultured cells to GnRHa (0.1
      or 10 nM, 60 min) resulted in a dose-related elevation of intracellular cAMP
      levels and taGTH release.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378801
TI  - Cystic fibrosis transmembrane conductance regulator and the etiology and
      pathogenesis of cystic fibrosis.
AB  - Cystic fibrosis (CF) is an inherited disorder causing pancreatic, pulmonary, and
      sinus disease in children and young adults. Abnormal viscosity of mucous
      secretions is a hallmark of the disease, and is believed to be the result of
      altered electrolyte transport across epithelial cell membranes. The monogenic
      etiology of this disease has been apparent for more than 40 years, but the
      defective gene has only recently been identified. This was made possible because
      of a revolution in genetic technology, called positional cloning, which can
      pinpoint disease genes without previous knowledge of the abnormal protein
      product. The protein encoded by the gene defective in CF has been termed the CF
      transmembrane conductance regulator (CFTR) because of its postulated role in
      electrolyte transport. Studies investigating the normal function of CFTR and how
      mutations affect that function, thereby causing CF, have required the combined
      skills of clinicians, geneticists, molecular biologists, and physiologists. From
      this collaborative effort a greater understanding of the pathogenesis of this
      disorder is now emerging. It may soon be possible to introduce novel therapies
      derived from this new knowledge that will be aimed directly at the basic defect.
      An ever-increasing number of genes of unknown function will be identified by
      continuing advances in molecular genetic technology and the advent of the genome
      sequencing project. The experience in cystic fibrosis research may prove to be a
      paradigm for investigation of the function of genes isolated by positional
      cloning methods.

PMID- 1378802
TI  - Altered content and distribution of tenascin in colitis, colon adenoma, and
      colorectal carcinoma.
AB  - Tenascin is a fibroblast product and extracellular matrix protein probably
      excerting a fibronectin-antagonizing role. Tenascin is broadly distributed
      interstitially during embryogenesis but restricted to a small range of structures
      in normal adult tissues. Using tenascin antibodies and an indirect
      immunoperoxidase method, normal colon, colitis, colon adenomas, and colorectal
      carcinomas were examined for tissue distribution of tenascin. Normal mucosa
      displayed a sparce meshwork of microfibrillar tenascin in the lamina propria. The
      basement membrane was tenascin negative at the bottom of the crypt and developed
      into a positive band steadily broadening towards the mucosal surface. In colitis,
      this polarity was effaced; the basement membrane was a broad tenascin-positive
      band nearly throughout while interstitial tenascin was moderately increased. Loss
      of polarity in tenascin content of the basement membrane was a constant feature
      of adenomas, inconsistently paralleled by structural alterations in surface
      qualities and continuity of tenascin pattern of the basement membrane. These were
      most pronounced in carcinomas, where this interface was often discontinuous and
      had a rough surface; in addition, interstitial tenascin was considerably
      increased. In carcinomas, the rough surface aspect of the tenascin pattern of the
      basement membrane was correlated with presence of lymph node metastases (P =
      0.04). It is concluded that alterations in tenascin pattern and content reflect
      complex disturbances in the interaction of inflamed/neoplastic colon epithelium
      and underlying matrix, leading to an organoid induction of tenascin in the
      inflammatory context and to induction together with structural abnormalities in
      neoplasia.

PMID- 1378803
TI  - Major histocompatibility class II expression on the small intestinal nervous
      system in Crohn's disease.
AB  - Widespread alterations of the gut autonomic nervous system have been described in
      Crohn's disease. Immunohistochemistry shows that these alterations are associated
      with the expression of major histocompatibility (MHC) class II antigens (HLA-DR)
      on enteroglial cells in the ganglia of the submucous and myenteric plexuses and
      on the enteroglial sheaths of the nerve extensions. Neuronal cell bodies and
      extensions do not express MHC class II antigens. The class II expression is
      associated with the presence of UCHL1-positive T lymphocytes. MHC class II
      expression can also be found on endothelial cells and vascular smooth muscle
      cells but not on smooth muscle cells of the muscularis mucosae or propria. The
      intensity of MHC class II expression on the glial cells of the enteric nervous
      plexus and on endothelial cells correlates well with the intensity of class II
      expression on epithelial cells.

PMID- 1378804
TI  - Hepatitis C virus antigen in hepatocytes: immunomorphologic detection and
      identification.
AB  - Hepatitis C virus (HCV) antigen was detected immunohistochemically using
      fluorescein isothiocyanate-labeled immunoglobulin G fractions from chimpanzee and
      human sera strongly reactive with recombinant hepatitis C virus structural and
      non-structural proteins. The antigen was localized in the cytoplasm of
      hepatocytes in all 9 chimpanzees with acute hepatitis C, in 5 of 10 chimpanzees
      with chronic HCV infection, and in 11 of 12 patients with chronic hepatitis C.
      The specificity of the hepatocellular HCV and FITC-labeled probes for HCV was
      ascertained by blocking studies with paired serum samples obtained from 8
      infected and uninfected chimpanzees or from 14 patients during the acute and
      chronic phases of HCV infection. Absorption experiments on FITC-labeled probes
      with selected host proteins (normal liver homogenate, plasma proteins, red blood
      cells) did not indicate cross reactivity of the probes with these antigens.
      Direct immunomorphologic evidence for the HCV specificity of hepatocellular HCV
      antigen deposits and the FITC-labeled polyclonal anti-HCVAg probe was established
      in absorption experiments using recombinant HCV nonstructural proteins. The
      putative HCV NS3 protein was the most prominent component of hepatocellular HCV
      antigen.

PMID- 1378805
TI  - Scientific advances in cystic fibrosis.

PMID- 1378806
TI  - Exons I and VII of the gene (Ker10) encoding human keratin 10 undergo structural
      rearrangements within repeats.
AB  - A genomic fragment containing the K51 gene previously isolated from a rat genomic
      library by hybridization with the v-mos probe in nonstringent conditions
      [Chumakov et al., Dokl. Akad. Nauk SSSR 290 (1986) 1252-1254], resembles a human
      keratin type-I-encoding gene [Shvets et al., Mol. Biol. 24 (1990) 663-677]. This
      genomic clone, K51, has been used as a probe to search for related human genes. A
      recombinant clone, HK51, with a 1.5-kb insert, was isolated from a human
      embryonic skin cDNA library, and its nucleotide (nt) sequence was determined.
      Analysis has shown that the cloned cDNA encodes human keratin 10 (Ker10). All
      presently known nt sequences of the human Ker10-encoding gene (Ker10) are not
      identical. Differences are concentrated in the 5'-end of the first exon and in
      the middle of the seventh exon within repeats. In spite of structural
      rearrangements in two of eight exons, the reading frame and position of the stop
      codon are preserved. The genetic rearrangements cause changes in hydrophobicity
      profiles of the N and C termini of Ker10. It was also noticed that insertion of
      one nt leads to the formation of an unusual 3'-end of the transcript.

PMID- 1378807
TI  - Characterization of a HeLa cDNA clone encoding the human SII protein, an
      elongation factor for RNA polymerase II.
AB  - We present the cloning and sequence characterization of a HeLa cDNA encoding the
      SII transcription elongation factor. This cDNA clone is distinct from those
      previously isolated from a human kidney cDNA library [Yoo et al., Nucleic Acids
      Res. 19 (1991) 1073-1079]. Southern analysis suggests that more than one gene may
      exist for SII in the human genome. A comparison of deduced amino acid sequences
      for SII-related proteins from a variety of eukaryotes demonstrates very high
      similarity, especially within the C-terminal domain.

PMID- 1378808
TI  - Association of hY4 pseudogenes with Alu repeats and abundance of hY RNA-like
      sequences in the human genome.
AB  - Three loci having homology with the small human cytoplasmic RNA, hY4, were
      isolated from human genomic DNA libraries and sequenced. Each sequence contains
      dispersed mismatches as compared with hY4 RNA, is followed by an A-rich or A + T
      rich sequence, and is bordered by direct repeats. Each of these loci, therefore,
      appears to constitute a small RNA class-III pseudogene. Surprisingly, two of the
      three loci are associated with Alu repeats. In the hY4.B7 locus, the hY4 sequence
      has integrated into the tail of an Alu element and in the hY4.F2 locus, an Alu
      sequence has inserted into the hY4 tail, confirming that A-rich tracts are
      preferential targets for retroposition. In addition, Southern blots with probes
      for each of the four hY RNAs indicate that hY RNA-like sequences are abundant in
      the human genome.

PMID- 1378809
TI  - [Lumbar intervertebral disk displacement. Results of conservative treatment].
AB  - Among 120 patients with lumbar disk prolapse treated conservatively over a seven
      year period, 72 patients were submitted to follow-up examination, and
      questionnaires completed by 92 patients were evaluated. Some 23.8% of the
      patients reported freedom from pain following treatment in hospital. Sciatica
      cleared up in 43.2%. After discharge from hospital, the average working time lost
      in 54 patients was 11.1 weeks. Ninety-five percent of the patients reported a
      return to work within one year. Eighty percent were able to return to their
      original workplaces. Some 73.8% of the patients surveyed were satisfied or very
      satisfied with the results of treatment. With respect to sensory disorders 37%,
      and with respect to paresis 32%, of the patients, reported improvement. Overall,
      the general and local symptoms, such as changes in gait and posture, percussion
      pain and tenderness, all showed an appreciably greater tendency to regress than
      did the neurological deficits.

PMID- 1378810
TI  - Effect of intraarterial active oxygen species on the rat pancreas.
AB  - To explore the role of active oxygen species in the development and progression
      of acute pancreatitis, we studied the direct toxic effect on the rat pancreas of
      active oxygen species: superoxide anions generated by xanthine/xanthine oxidase
      (X/XO), and hydrogen peroxide (H2O2). After a continuous injection of X (10(-3)M,
      0.9 ml/hour)/XO (1 U/ml, 0.3 ml/hour) into the celiac artery supplying the
      pancreas, hemorrhages and extensive edema developed in the pancreas. The amylase
      and lipase concentrations in the peritoneal fluid rose to 10.3 and 13.8 times the
      control values, respectively. The subsequent infusion of superoxide dismutase
      (SOD, 3600 U/hour) into the external jugular vein completely suppressed
      hemorrhages, and reduced edema and the amylase and lipase concentrations in the
      peritoneal fluid. After continuous injection of H2O2 (100 microM, 1.2 ml/hour),
      via the celiac artery, marked hemorrhages and edema appeared in the pancreas, and
      the amylase and lipase concentrations in the peritoneal fluid were 11.1 and 17.3
      times higher than the control values, respectively. These abnormalities were
      significantly suppressed by the intravenous infusion of catalase (10 mg/kg/hour)
      or gabexate mesilate (10 mg/kg/hour). These results indicate that active oxygen
      species have a direct toxic effect on the pancreas and that free radicals may
      play an important role in the development of acute pancreatitis.

PMID- 1378811
TI  - Prevalence of hepatitis C virus antibodies in hemodialysis patients and dialysis
      staff.
AB  - To estimate the prevalence of hepatitis C virus (HCV) infection in dialysis
      patients, serum anti-HCV antibodies were evaluated in 489 Japanese patients
      undergoing hemodialysis, and 152 members of the hospital dialysis staff by enzyme
      linked immunosorbent assays for anti-C100, anti-KCL-163 (HCV nonstructural
      protein), and anti-JCC (translation product of the presumptive HCV core gene). Of
      the 489 hemodialysis patients, 100 (20.4%) were positive for anti-C100, 107
      (21.9%) for anti-KCL-163, and 168 cases (34.4%) for anti-JCC. These rates were
      significantly higher than those for either the hospital staff or the healthy
      blood donors. Forty-two per cent of the dialysis patients were anti-HCV positive
      by at least one assay, suggesting that HCV infection is more common among this
      population than previously thought. Positivity for anti-HCV was related to the
      duration of hemodialysis. Elevated alanine aminotransferase levels were present
      in 12.5% of the dialysis patients, 77% of whom were also anti-HCV positive. The
      positivity rates among the 152 members of the hospital staff were 0.7% for anti
      C100, 2.6% for anti-KCL-163, and 8.6% for anti-JCC, with the anti-JCC rate of
      positivity exceeding that of the healthy blood donors.

PMID- 1378812
TI  - In vitro secretion of calcitonin from a rat C cell line: effect of repetitive
      stimulation with the calcium channel agonist BAY K 8644.
AB  - Calcium and BAY K 8644 acutely stimulate calcitonin secretion by influx of
      extracellular calcium (Ca) through voltage-dependent calcium channels, leading to
      an increase in cytosolic free Ca. Repetitive exposure to BAY K 8644 (10(-6) M)
      resulted in an increase in calcitonin (CT) secretion in the rat C-cell line (rMTC
      6-23) lasting 9 hours, in comparison to that of 3 mM Ca2+ which lasted 6 hours.
      Equimolar concentration of nifedipine did not inhibit the stimulatory effect of
      BAY K 8644 as compared to the nifedipine only group. The decrease in stimulated
      CT secretion during long-term exposure to BAY K 8644 is due to desensitization of
      cells which may be attributed to down-regulation of dihydropyridine receptors.
      After 12 h exposures to 3 mM Ca2+ alone, BAY K 8644 (10(-6) M) alone or in
      combination with nifedipine (10(-6) M), CT content decreased below the control
      level, indicating a decrease in synthesis. Overall cellular protein content was
      not affected by the test agents. Repetitive exposure of C-cells to BAY K 8644
      revealed a desensitization of the stimulatory effect on CT secretion and a
      decrease in CT cell content.

PMID- 1378813
TI  - Growth hormone-binding protein in patients with anorexia nervosa determined in
      two assay systems.
AB  - To learn the mechanism of low plasma insulin-like growth factor-I (IGF-I) despite
      high growth hormone (GH) secretion in patients with anorexia nervosa, we assessed
      human serum GH-binding protein (BP) (GH-BP), which has been shown to be identical
      to the extracellular domain of GH receptor, and therefore might reflect
      peripheral GH receptor expression (i.e. there is a significant linear correlation
      between GH-BP and IGF-I at less than 2.0 U/ml in healthy children). The serum GH
      BP level was determined by gel filtration and confirmed by immunoassay using GH
      receptor monoclonal antibody. Furthermore, we analyzed serum IGF-binding proteins
      (IGFBPs) by the affinity cross-linking method to determine the GH-IGF-I axis in
      this condition. Measurement of GH-BP by the two assays gave identical results,
      suggesting that serum GH-BP corresponds to the extracellular domain of GH
      receptor. The low GH-BP and high IGFBP levels in patients with anorexia nervosa
      shown in this study, which were normalized by an improved nutritional state,
      would indicate resistance to GH as well as to IGFs in this condition, in which
      the former is in part compensated by high GH levels while the latter is not.

PMID- 1378814
TI  - Whipple's disease: a histological, immunocytochemical and electronmicroscopic
      study of the immune response in the small intestinal mucosa.
AB  - Whipple's disease is a multisystem disorder with protean manifestations and with
      poorly understood aetiopathogenesis. It is unclear how the immune system reacts,
      whether it functions normally or not, whether it protects the organism or is
      defeated in one way or another by the 'Whipple bacillus'. The purpose of our
      study was to assess humoral and cellular immunity at the level of the intestinal
      mucosa. This histochemical, immunocytochemical and electronmicroscopic study,
      based on 16 cases, has shown that the changes in components of the mucosal immune
      system in Whipple's disease are quite different from normal. The phagocytic
      capacity of the macrophages, assessed microscopically, is abnormal, the number of
      intra-epithelial lymphocytes is increased, the CD 4/CD 8 cell ratio is decreased
      and the IgM positive cells in the lamina propria outnumber the IgA positive
      cells. These changes may be inter-dependent.

PMID- 1378815
TI  - Immune regulation by brain cells in the central nervous system: microglia but not
      astrocytes present myelin basic protein to encephalitogenic T cells under in vivo
      mimicking conditions.
AB  - The antigen-presenting capability of various types of brain cell, such as primary
      mixed glial cells, astrocytes and microglia, was examined under conditions in
      which Ia antigen expression on the cultured cells mimicked that in the central
      nervous system (CNS) of rats with experimental autoimmune encephalomyelitis
      (EAE). In the CNS of rats with EAE, microglia but not astrocytes express Ia
      antigens. To produce such conditions, cultured brain cells were treated with
      various concentrations of interferon-gamma (IFN-gamma). It was revealed that in
      vivo-like conditions were produced when cultured brain cells were treated with
      less than 100 U/ml IFN-gamma. Under such conditions, microglia presented an
      antigen, myelin basic protein (MBP), to MBP-specific T-cell lines. Astrocytes, on
      the other hand, did not show antigen-presenting ability, but rather suppressed T
      cell proliferation. Primary mixed glial cells, mainly comprising astrocytes and
      microglia, were also weak antigen-presenting cells (APC). These findings suggest
      that brain cells comprising various types of cell with regard to APC function do
      not up-regulate the proliferation of encephalitogenic T cells in vivo, although a
      particular type of brain cell, i.e. microglia, show antigen-presenting
      capability.

PMID- 1378816
TI  - Dendritic cells efficiently immunoselect mycobacterial-reactive T cells in human
      blood, including clonable antigen-reactive precursors.
AB  - Given the persistence of tuberculosis throughout the world, the delineation of
      mechanisms that lead to protective immunity to Mycobacterium tuberculosis is
      important. We have evaluated the presenting function of human dendritic cells for
      mycobacterial antigens, since these antigen-presenting cells (APC) are
      particularly effective in initiating antigen-specific T-cell responses. Dendritic
      cells from blood prove to be active APC for mycobacteria-specific proliferative
      responses by CD4+ T cells from bacillus Calmette-Guerin (BCG)-vaccinated
      individuals. In the first 24-48 hr of the response, dendritic cells that have
      been pulsed with mycobacterial antigens, including live BCG, effectively bind T
      cells forming discrete cell clusters. The clusters represent about 1% of the
      applied T cells. Clusters are highly enriched in mycobacterial reactivity while
      the non-clusters are depleted. Clustered T cells can be used as a starting point
      to expand antigen-specific cell lines. Mitogen and allogeneic feeder cells were
      used as APC to expand the mycobacterial-reactive lines, because the antigen
      specific T cells had been preselected by virtue of their binding to antigen
      pulsed dendritic cells. We discuss the advantages of obtaining antigen-reactive T
      cells by using dendritic cells as immunoadsorbents. These lines should help
      delineate the range of mycobacterial antigens and T-cell responses that
      participate in host responses to mycobacteria.

PMID- 1378817
TI  - Expression of soluble isoforms of rat CD45. Analysis by electron microscopy and
      use in epitope mapping of anti-CD45R monoclonal antibodies.
AB  - The CD45 or leucocyte-common antigens are encoded by a single gene but can be
      found in various forms due to alternative splicing of three exons near the 5' end
      of the gene. The CD45 antigens are major glycoproteins of all types of
      leucocytes. Monoclonal antibodies recognizing restricted epitopes of CD45 have
      been used to distinguish phenotypic and functional subsets of lymphocytes. To
      facilitate epitope mapping and biochemical studies, we have expressed the
      extracellular portions for four different isoforms of rat CD45 in Chinese hamster
      ovary cells. Constructs were prepared to give four soluble CD45 isoforms, with
      sequence incorporating either all three alternative exons (sCD45.ABC), the B exon
      (sCD45.B), the C exon (sCD45.C), or no alternative exons (sCD45.O). These were
      expressed at approximately 5 mg/l of spent tissue culture supernatant and were
      antigenically active with monoclonal antibodies (mAb) that recognize all CD45
      isoforms. The MRC OX22 and OX32 mAb have been used to split rat CD4+ T cells into
      functionally distinct subpopulations and the epitopes for these were mapped to
      the product of exon C. The epitope for MRC OX33, a marker for B cells, requires
      expression of either the A exon or the A/B exon junction. Electron microscopy
      showed that the extra segments contributed to an extended structure as has been
      predicted from the sequence. The shape of the molecule is discussed with regard
      to other molecules at the leucocyte cell surface.

PMID- 1378818
TI  - Reactivity of anti-human C-reactive protein (CRP) and serum amyloid P component
      (SAP) monoclonal antibodies with limulin and pentraxins of other species.
AB  - Limulus polyphemus C-reactive protein (CRP) (limulin) has approximately 30% amino
      acid sequence homology and shares at least one idiotypic determinant associated
      with ligand-binding activity with human CRP (hCRP); limulin also shares amino
      acid sequence homology and lectin activity with human serum amyloid P component
      (hSAP). In the present study panels of 14 anti-hCRP monoclonal antibodies (mAb)
      directed to distinct hCRP epitopes and 11 anti-hSAP mAb directed to distinct
      epitopes of hSAP were tested for reactivity with limulin and pentraxins of other
      species including rabbit CRP (raCRP), rat CRP and hamster female protein (FP) by
      ELISA and Western blot analyses. None of the anti-human pentraxin mAb showed
      strong cross-reactivity with limulin; only five mAb reacted with limulin at all,
      and cross-reactivities of these mAb with the other pentraxins, when present, also
      were weak. Cross-reactivity of limulin with hCRP and hSAP was similar, and in
      light of comparable amino acid sequence homology, suggests this molecule can be
      considered the limulus SAP as well as the limulus CRP. Several anti-hCRP mAb
      cross-reacted strongly with rabbit CRP and rat CRP; a few anti-hSAP cross-reacted
      strongly with FP; and weak cross-reactions were observed between hCRP and hSAP,
      but cross-reactivities between the pentraxins generally were limited and weak. A
      rabbit polyclonal antibody raised to highly conserved limulin peptide 141-156 and
      strongly reactive with limulin reacted weakly with hCRP and raCRP but failed to
      react with rat CRP, hSAP or FP. These studies emphasize a limited but distinct
      antigenic similarity between limulin, hCRP and other pentraxins, and identify mAb
      reactive with potential regions of shared structure and/or function between
      pentraxins of different species.

PMID- 1378819
TI  - Tinea versicolor: histologic and ultrastructural investigation of pigmentary
      changes.
AB  - A comparative histopathologic study is made between the hypopigmented and
      hyperpigmented skin lesions of pityriasis versicolor and normal skin areas
      utilizing histochemical stains and electron microscopy. There were no differences
      found between the population of Dopa-positive melanocytes within the
      hypopigmented and hyperpigmented lesions and the normal skin areas. The total
      epidermal pigmentation was diminished in hypopigmented lesions. The keratin layer
      was found to be significantly thicker in hyperpigmented lesions and contained
      more organisms. In hypopigmented lesions, melanocytes contained fewer and smaller
      melanosomes and exhibited signs of degenerative cellular changes.

PMID- 1378820
TI  - Cutaneous lupus erythematosus: direct immunofluorescence and epidermal basal
      membrane study.
AB  - Biopsy specimens of cutaneous discoid lesions of 71 patients with cutaneous lupus
      erythematosus (CLE) were studied. The material was examined by direct
      immunofluorescence (DIF) to establish positivity and morphologic patterns of
      immunoglobulins and complement deposits in the basement membrane zone (BMZ). A
      correlation between DIF results and thickening of the epidermis basement membrane
      (BM) stained by periodic acid-Schiff (PAS), obtained from 31 matched biopsy
      specimens, also is presented. Direct immunofluorescence had positive results in
      66.20% of the 71 examinations and 70.97% of the matched examinations, whereas PAS
      showed BM thickening in 100% of the specimens. This observation stresses the
      importance of such histopathologic findings in the diagnosis of discoid lesions
      in CLE. There was no correlation between DIF patterns and PAS-stained BMZ
      thickening. These findings merit additional study. In conclusion, an accordance
      between PAS-stained BM thickening and immunoglobulin deposits has occurred in
      70.97% of cases. This phenomenon does not depend on the presence of
      immunocomplexes, for it occurs even in cases in which immunocomplex deposits were
      not detected.

PMID- 1378821
TI  - Studies on antigenic variability of C strains of foot-and-mouth disease virus by
      means of synthetic peptides and monoclonal antibodies.
AB  - Peptides representing the sequence of the immunodominant loop of foot-and-mouth
      disease virus strain C-S8 (YTASARGDLAHLTTTHARHLP, residues 136-156 of VP1) and of
      several variant viruses have been prepared by solid phase methods. In addition,
      five peptides with single-residue replacements at Leu147 (Ile, Nle, Val, Ala,
      Gly) have been synthesized. Tosyl and dinitrophenyl protections for histidine
      have been compared, the latter being found to give better synthetic products. The
      peptides have been tested in an immunodot assay against a panel of monoclonal
      antibodies directed towards the VP1 loop. Immunochemical results are discussed on
      the basis of the mobility of the region reproduced by the peptides and the nature
      of the side chain of residue 147.

PMID- 1378822
TI  - Replacement of Tyr-SO3H by a p-carboxymethyl-phenylalanine in a CCK8-derivative
      preserves its high affinity for CCK-B receptor.
AB  - The sulfated tyrosine present in the sequence of CCK8 Asp26-Tyr(SO3H)-Met-Gly-Trp
      Met-Asp-PheNH2, seems to play a critical role in the recognition of CCK-A binding
      sites. In this work, we have investigated whether the presence of an anionic
      charge on the tyrosine moiety is strictly necessary and whether the sulfate
      moiety interacts with a divalent cation in the receptor subsite. For this
      purpose, the novel amino acids (L,D)Phe(p-CH2CO2H) and (L,D) Phe(p-CH2CONHOH), as
      well as their L-resolved forms were introduced into the sequence of Ac[X27,
      Nle28, Nle31]-CCK27-33 by solid phase method. The biological activities of these
      new derivatives were compared to two almost equiactive analogues of CCK8,
      Ac[Phe(p-CH2SO3H)27, Nle28, Nle31]-CCK27-33 and Boc[Nle28, Nle31]-CCK27-33 (BDNL)
      and to the nonsulfated analogue of the latter peptide (BDNL NS). All these new
      CCK-related analogues behave as agonists in stimulating pancreatic amylase
      release and display high affinity for brain binding sites (KI approximately 3-11
      nM) but the only peptides which retain affinity for CCK-A receptors (KI
      approximately 20 nM) are those containing a p-carboxymethyl phenylalanine. Thus,
      introduction of this amino acid under an esterified form on the side chain, into
      specific and potent CCK-B agonists could allow compounds endowed with good
      bioavailabilities to be obtained.

PMID- 1378823
TI  - Distribution of efferent neurons projecting to the tectum and cerebellum in the
      rat prepositus hypoglossi nucleus.
AB  - Distributions of efferent neurons projecting to the superior colliculus (SC), the
      pretectum, and the cerebellar cortex were studied in the rat prepositus
      hypoglossi nucleus (PRH) by retrograde labeling with wheat germ agglutinin
      horseradish peroxidase (WGA-HRP). After injection of the tracer into the
      unilateral SC, small- and medium-sized neurons were labeled throughout the entire
      rostrocaudal extent of the PRH, with the highest proportion in the middle part of
      the nucleus. After application of WGA-HRP to the unilateral pretectal region,
      including the nucleus of the optic tract, numerous labeled neurons appeared in
      the bilateral PRH. The highest distribution was found in the most rostral part of
      this nucleus. Furthermore, small neurons of the supragenual nucleus of the facial
      nerve also were labeled. Injection of WGA-HRP into lobules VI-VII of the
      cerebellar vermis resulted in the labeling of mainly medium-sized neurons in the
      bilateral PRH, primarily in the caudal third. WGA-HRP-labeled neurons were less
      frequently observed in the PRH after unilateral injection into the flocculus and
      paraflocculus. Retrograde double labeling by fluorescent dyes showed that a few
      neurons in the middle part of the PRH sent divergent axons to vermal lobules VI
      VII and the SC.

PMID- 1378824
TI  - Simultaneous quantification of DNA and RNA in tissue sections. A comparative
      analysis of the methyl green-pyronin technique with the gallocyanin chromalum and
      Feulgen procedures using image cytometry.
AB  - For simultaneous cytophotometric measurement of DNA and RNA, the standardized
      Methyl Green-Pyronin Y technique is an obvious choice. It is, however, first
      necessary to correlate the uptake of Pyronin Y to the staining intensity of RNA.
      The material consisted of paraffin sections of formalin- or Carnoy-fixed rat
      liver. The sections were pretreated with water, buffer, deoxyribonuclease,
      ribonuclease, or both enzymes in sequence, and stained with the standardized
      Methyl Green-Pyronin Y procedure, Gallocyanin chromalum, or the Feulgen reaction.
      Sections stained directly without pretreatment served as controls. Staining
      intensities were measured with an image analyser for cell nuclei, nucleoli and
      cytoplasm. After deoxyribonuclease treatment, nuclear staining intensity with
      Methyl Green, Gallocyanin chromalum, and Schiff's reagent dropped nearly to zero.
      The same was seen for both nucleoli and cytoplasm with Pyronin Y and Gallocyanin
      chromalum after ribonuclease treatment. Staining intensity of Pyronin Y
      correlated directly with that of Gallocyanin chromalum for nucleoli and
      cytoplasm. After ribonuclease treatment, a direct correlation was found between
      the nuclear staining intensity of Methyl Green and nuclear absorption of
      Gallocyanin chromalum. We conclude that the standardized Methyl Green-Pyronin Y
      stain is reliable for the simultaneous quantitative assessment of both RNA and
      DNA. The simplicity of this technique makes it a valuable tool even for daily
      routine.

PMID- 1378826
TI  - Effects of video-assisted training on employment-related social skills of adults
      with severe mental retardation.
AB  - Two studies investigated effects of video-assisted training on employment-related
      social skills of adults with severe mental retardation. In video-assisted
      training, participants discriminated a model's behavior on videotape and received
      feedback from the trainer for responses to questions about video scenes. In the
      first study, 3 adults in an employment program participated in video-assisted
      training to request their supervisor's assistance when encountering work
      problems. Results indicated that participants discriminated the target behavior
      on video but effects did not generalize to the work setting for 2 participants
      until they rehearsed the behavior. In the second study, 2 participants were
      taught to fix and report four work problems using video-assisted procedures.
      Results indicated that after participants rehearsed how to fix and report one or
      two work problems, they began to fix and report the remaining problems with video
      assisted training alone.

PMID- 1378825
TI  - Studies on the distribution of calcitonin gene-related peptide-like and substance
      P-like immunoreactivities in rat hind limb muscles.
AB  - The tibialis anterior, extensor digitorum longus and soleus muscles in the rat
      were examined with respect to the presence of calcitonin gene-related peptide
      like as well as substance P-like immunoreactivity. In some of the motor endplates
      in these muscles, identified by staining for acetylcholinesterase activity,
      calcitonin gene-related peptide-like immunoreactivity was detected, but in others
      it was not. Calcitonin gene-related peptide-like immunoreactivity was found to
      coexist with substance-P-like immunoreactivity in nerve fibres located outside
      and inside the capsule of the muscle spindles, as well as in nerve fibres located
      in nerve fascicles. These fibres presumably represent sensory nerve fibres.
      Calcitonin gene-related peptide-like immunoreactivity, but not substance P-like
      immunoreactivity, was also detected in cap-like structures located on the surface
      of the intrafusal muscle fibres in the polar regions of the spindles, structures
      which are likely to correspond to motor plate endings. The observations suggest
      that calcitonin gene-related peptide is heterogeneously present in the endplates
      of rat hind limb muscles, and gives for the first time immunohistochemical
      evidence for the presence of calcitonin gene-related peptide and substance P in
      the innervation of muscle spindles.

PMID- 1378827
TI  - Effects of community-based, videotape, and flash card instruction of community
      referenced sight words on students with mental retardation.
AB  - Community-referenced sight words and phrases were taught to adolescents with mild
      and moderate mental retardation using three instructional methods in two
      locations. Words were presented on flash cards in a school setting, on videotape
      recordings in a school setting, and on naturally occurring signs in the
      community. During each session, participants were taught one third of the words
      in each of these conditions and were then tested at the community sites. A
      constant prompt delay procedure was used to promote stimulus control to the
      experimenter's cue initially and then to transfer control to the textual stimuli
      used for training. A multiple baseline across participants design was employed.
      Results showed rapid acquisition of the community-referenced sight words in all
      three training conditions and generalization from the flash card and videotape
      conditions to the community sites.

PMID- 1378828
TI  - Rare spontaneously transformed human endothelial cell line provides useful
      research tool.

PMID- 1378829
TI  - Distribution of fibroblast growth factors in cultured tumor cells and their
      transplants.
AB  - The distributions of acidic fibroblast growth factor (aFGF) and basic FGF (bFGF)
      in extracts of various cultured mammalian cells were determined from their
      elution profiles on heparin-affinity chromatography, and assay of activity as
      ability to stimulate DNA synthesis in BALB/c3T3 cells. Only aFGF was found in
      extracts of mouse melanoma B 16 cell and rat Morris hepatoma cell (MH1C1) lines.
      Other tumor cell lines established from solid tumors and some normal cells
      contained bFGF as a main component, but blood tumor cell lines contained no aFGF
      or bFGF. The FGFs in extracts of solid tumor tissues derived by transplantations
      of these cultured tumor cells and various normal tissues of mice were also
      examined. Tumors formed by all cell lines, regardless of whether they produced
      aFGF, bFGF, or neither, contained bFGF that was probably derived from host cells
      including capillary endothelial cells, in addition to the tumor-derived aFGF or
      bFGF, if produced. The content of bFGF, possibly derived from the host, in these
      tumor tissues was comparable to those of various mouse organs other than thymus,
      lung, spleen, and testis, which have higher bFGF contents. Tumor tissues derived
      from cultured cells producing bFGF had relatively higher bFGF contents. Like
      bFGF, aFGF was distributed almost ubiquitously in normal mouse tissues.

PMID- 1378830
TI  - Growth of a human yolk sac tumor cell line with yolk sac-derived functions in
      selenium-supplemented chemically defined synthetic medium.
AB  - A human yolk sac tumor cell line, TG1, which was established from a testicular
      yolk sac tumor, was found to replicate continuously in a chemically defined
      medium supplemented with Na2SeO3 (ISRPMI). TG1 produced several plasma proteins
      and growth factors: albumin, alpha-fetoprotein (AFP), ferritin, carcinoembryonic
      antigen, beta-2-microglobulin, polyamine, neuron specific enolase, tissue
      polypeptide antigen, transferrin (Tf), epidermal growth factor, and platelet
      derived growth factor. By analysis of lentil lectin (LcHA)-affinity
      electrophoresis, to examine the microheterogeneity of carbohydrate chains of
      synthetic glycoproteins, TG1 cells cultured with ISRPMI produced only LcHA
      reactive Tf and AFP based on core fucose attached to asparagine-linked N
      acetylglucosamine residues instead of LcHA-nonreactive Tf and AFP produced by TG1
      cells cultured with fetal bovine serum (FBS)-containing medium. alpha 1-6
      Fucosyltransferase activity was significantly greater in the TG1 cells cultured
      with ISRPMI (39.9 +/- 1.5 pmol.h-1.mg-1 protein) than cultured with FBS
      containing media (18.2 +/- 1.2 pmol.h-1.mg-1 protein). These results have
      indicated that the selective increase of alpha 1-6 fucosyltransferase occurred
      when the cells were cultured with the FBS-free synthetic media.

PMID- 1378831
TI  - Oral and poster presentations.

PMID- 1378832
TI  - Cloning and expression of a cDNA encoding human endothelium-derived relaxing
      factor/nitric oxide synthase.
AB  - Nitric oxide, which accounts for the biological activity of endothelium-derived
      relaxing factor (EDRF), is synthesized in endothelial cells from L-arginine by
      nitric oxide synthase (NOS). We report here the cloning and functional expression
      of a cDNA encoding human endothelial NOS. Oligonucleotides corresponding to amino
      acid sequences shared by cytochrome P450 reductase and the recently identified
      brain NOS were synthesized to amplify a partial cDNA encoding a bovine
      endothelial cell NOS-related protein. This partial cDNA was used to isolate a
      cDNA encoding a human vascular endothelial NOS. The translated human protein is
      1294 amino acids long and shares 52% of its amino acid sequence with brain NOS.
      Using RNA blot hybridization, abundant endothelial NOS mRNA was detected in
      unstimulated human umbilical vein endothelial cells. To determine the functional
      activity of the endothelial protein, we ligated the cDNA into an expression
      vector and transfected it into NIH3T3 cells. Cells expressing this cDNA contained
      abundant NADPH diaphorase activity, a histochemical marker for NOS. In co-culture
      assays, nitric oxide production by transfected cells increased guanylate cyclase
      activity in reporter rat fetal lung fibroblasts. In addition, NOS-catalyzed
      conversion of arginine to citrulline in transfected cells was significantly
      increased by A23187, a calcium ionophore. Isolation of a cDNA encoding a calcium
      regulated, constitutively expressed human endothelial NOS, capable of producing
      EDRF in blood vessels, will accelerate the characterization of the role of this
      enzyme in normal and abnormal endothelial regulation of vascular tone.

PMID- 1378833
TI  - Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds
      urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha
      2-macroglobulin receptor mediates cellular degradation of urokinase receptor
      bound complexes.
AB  - Complexes between 125I-labeled urokinase-type plasminogen activator (uPA) and
      plasminogen activator inhibitor type-1 (PAI-1) bound to purified alpha 2
      macroglobulin (alpha 2M) receptor (alpha 2MR)/low density lipoprotein receptor
      related protein (LRP). No binding was observed when using uPA. The magnitude of
      uPA.PAI-1 binding was comparable with that of the alpha 2MR-associated protein
      (alpha 2MRAP). Binding of uPA.PAI-1 was blocked by natural and recombinant alpha
      2MRAP, and about 80% inhibited by complexes between tissue-type plasminogen
      activator (tPA) and PAI-1, and by a monoclonal anti-PAI-1 antibody. In human
      monocytes, uPA.PAI-1, like uPA and its amino-terminal fragment, bound to the
      urokinase receptor (uPAR). Degradation of uPAR-bound 125I-uPA.PAI-1 was 3-4-fold
      enhanced as compared with uncomplexed uPAR-bound uPA. The inhibitor-enhanced uPA
      degradation was blocked by r alpha 2MRAP and inhibited by polyclonal anti-alpha
      2MR/LRP antibodies. This is taken as evidence for mediation of internalization
      and degradation of uPAR-bound uPA.PAI-1 by alpha 2MR/LRP.

PMID- 1378834
TI  - Phospholemman expression induces a hyperpolarization-activated chloride current
      in Xenopus oocytes.
AB  - A new type of chloride channel has been identified by functional expression of
      phospholemman, a 72-amino acid cardiac sarcolemmal protein with a single
      transmembrane domain. Xenopus oocytes injected with phospholemman RNA developed a
      chloride-selective current, which was activated by hyperpolarizing pulses. The
      current activated very slowly with a pronounced sigmoidal delay, did not
      inactivate, and increased in amplitude with trains of pulses, depolarized holding
      potentials, and low extracellular pH. Point mutations within the single
      transmembrane region abolished the sigmoidal delay of expressed currents.
      Phospholemman appears to be the smallest plasma membrane channel protein yet
      known. The structure is dissimilar to any chloride channel described thus far.

PMID- 1378835
TI  - The cystic fibrosis transmembrane regulator is present and functional in
      endosomes. Role as a determinant of endosomal pH.
AB  - Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis
      transmembrane conductance regulator (CFTR), which lead to defective Cl-
      conductance in epithelial cells. While the CFTR gene product has been detected in
      the plasma membrane, its presence and functional role in the membranes of
      intracellular compartments remain to be established. The purpose of the present
      experiments was to functionally localize CFTR in the endosomal membrane and to
      test the role of the associated Cl- conductance in the regulation of endosomal pH
      (pH(en)). When using conductive protonophores, the net H+ flux across the
      endosomal membrane of Chinese hamster ovary (CHO) cells is limited by the
      movement of counterions. Thus, ionic permeability could be estimated indirectly,
      from the changes in pH(en) determined fluorimetrically. Measurements in situ and
      in a cell-free microsomal preparation indicate the presence of a protein kinase A
      (PKA)-activated anion conductance in endosomes from CHO cells transfected with
      CFTR, but not in endosomes from wild-type or mock-transfected cells. In endosomes
      isolated from CFTR-expressing cells, the stimulatory effect of PKA was diminished
      by a specific peptide inhibitor of PKA, by alkaline phosphatase treatment or by a
      monoclonal antibody against the second nucleotide binding fold of CFTR.
      Increasing counterion permeability by phosphorylation of CFTR or by addition of
      valinomycin failed to alter the rate or extent of endosomal acidification in
      situ. Our observations indicate that functional CFTR, susceptible to activation
      by PKA, is present in endosomes of transfected CHO cells. More importantly, the
      data suggest that factors other than counterion permeability are the major
      determinants of pH(en).

PMID- 1378836
TI  - Differential expression of adenine nucleotide translocator isoforms in mammalian
      tissues and during muscle cell differentiation.
AB  - The adenine nucleotide translocator (ANT) catalyzes the exchange of ADP and ATP
      across the mitochondrial internal membrane. Its three isoforms, ANT1, ANT2, and
      ANT3 are coded by differentially regulated nuclear genes. The patterns of
      expression of these genes in human, bovine, and mouse tissue are similar. ANT1 is
      highly expressed in heart and skeletal muscle and is induced during myoblast
      differentiation. It is coordinately regulated with the nuclear gene for the
      mitochondrial ATP synthase beta subunit, with which it shares the positive muscle
      cis element, the OXBOX. ANT2 is either absent or weakly expressed in all tissues.
      ANT3 is ubiquitously expressed in all tissues, and its transcript level is
      proportional to the level of oxidative metabolism. The tissue-specific expression
      of the ANT gene family thus provides insight into the molecular basis of the
      differential reliance of mammalian tissues on oxidative phosphorylation.

PMID- 1378837
TI  - Structure-function relationships of HIV-1 reverse transcriptase determined using
      monoclonal antibodies.
AB  - The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is
      one of the main targets in approaches to the chemotherapy of AIDS. A detailed
      knowledge of structure-function relationships of this enzyme is a prerequisite
      for rational drug design. We have used monoclonal antibodies as tools to identify
      functionally important regions of the protein. The preparation of 23 murine
      monoclonal antibodies (mAb) against HIV-1 reverse transcriptase and their
      different effects on the enzyme are described. The interaction of purified mAbs
      with HIV-1 RT was demonstrated by enzyme-linked immunosorbent assay (ELISA),
      Western blots, and high performance liquid chromatography size exclusion
      chromatography. One of the antibodies also recognized recombinant HIV-2 RT.
      Antibody binding epitopes on HIV-1 RT were analyzed by immunoblotting using
      cyanogen bromide fragmented RT, C-terminally truncated mutants, and a peptide
      ELISA employing 15-mer synthetic overlapping peptides spanning nearly the
      complete polypeptide chain. The epitopes were mapped within three domains
      corresponding to amino acids 200-230, 300-428, and 528-560. Two mAbs show
      neutralizing properties on enzymatic functions of RT. One affects the polymerase
      activity and to a certain degree the RNase H activity of the enzyme, whereas the
      other inhibits the latter activity exclusively. mAb 28, which blocks the
      polymerase activity, interferes with the nucleotide binding region of RT, as
      shown by fluorescence spectroscopy using a labeled template/primer complex. By
      investigating the antibody effects on dimer formation of the heterodimeric
      enzyme, three domains corresponding to amino acids 230-300, 350-428, and residues
      around amino acid 540 involved in protein-protein interactions were localized.

PMID- 1378838
TI  - Antigenic determinants of senescent antigen of human erythrocytes are located in
      sialylated carbohydrate chains of Band 3 glycoprotein.
AB  - Naturally occurring IgG autoantibody against Band 3 glycoprotein of human
      erythrocyte membrane (anti-Band 3) recognizes the erythrocytes modified with
      oxidizing or SH-blocking agents as well as senescent erythrocytes. Location of
      the antigenic determinants of Band 3 this autoantibody recognizes was
      investigated by competitive inhibition studies of the antibody binding to the
      modified cells. Autologous IgG binds to the modified erythrocytes, and purified
      Band 3 totally inhibits the binding. This inhibitory activity of Band 3 was not
      affected by digestion of Band 3 with various proteases. Treatment of Band 3 with
      endo-beta-galactosidase that destroys the poly-N-acetyllactosaminyl sugar chain
      of Band 3 or with neuraminidase resulted in loss of the inhibitory activity.
      Oligosaccharides released from Band 3 by hydrazinolysis effectively inhibited the
      binding of autologous IgG and 125I-labeled purified anti-Band 3 to the modified
      cells, whereas the oligosaccharides depleted of acidic components did not. Endo
      beta-galactosidase and neuraminidase destroyed the activity of the
      oligosaccharides, but alpha-L-fucosidase did not. Furthermore, human lactoferrin
      that contains sialylated two N-acetyllactosaminyl units also exhibited potent
      inhibitory activity, and the activity was destroyed by endo-beta-galactosidase
      and neuraminidase. These results indicate that the antigenic determinants of Band
      3 are located in sialylated poly-N-acetyllactosaminyl sugar chains. Based on this
      finding, mechanism of appearance of the antigen on senescent erythrocytes
      recognized by anti-Band 3 (senescent antigen) was discussed.

PMID- 1378839
TI  - Identification of cis-regulatory elements in the myelin proteolipid protein (PLP)
      gene.
AB  - Regulatory elements of the proteolipid protein (PLP) gene were identified
      physically by footprinting and gel mobility shift assays and functionally by
      transfecting glial cell lines with PLP-chloramphenicol acetyltransferase chimeric
      genes. In both human and rat glial cells, only several hundred base pairs of
      upstream sequence were sufficient for high level activity of the human PLP
      promoter. This region contains five sites that contact nuclear proteins in vitro.
      More distal recognition sites may exist, as regions upstream of -524 displayed
      silencing activity indicative of a negative regulatory element. A series of site
      directed mutations revealed one essential positive element (ATGGA at -118) which
      is found in other genes encoding myelin proteins. Our combined biochemical and
      functional analyses indicate that the key cis sites for maximal tissue-specific
      expression of PLP in cultured glial cells are clustered near the promoter. Within
      this cluster are several conserved motifs that may coordinate the regulation of
      myelin-specific genes.

PMID- 1378840
TI  - Transcriptional and post-translational regulation of beta 1 integrin expression
      during keratinocyte terminal differentiation.
AB  - During suspension-induced terminal differentiation of human epidermal
      keratinocytes, the alpha 5 beta 1 integrin is down-regulated in two stages:
      first, the ability of the receptor to bind fibronectin is reduced; later, the
      receptor is lost from the cell surface, and the level of the subunit mRNAs
      declines. We have begun to examine the mechanisms that regulate these events.
      Pulse-chase experiments showed that when keratinocytes were placed in suspension
      to induce terminal differentiation maturation of the beta 1 subunit and its
      associated alpha subunits was prevented. The inhibition of maturation was at the
      stage of N-linked glycosylation in the Golgi, because the immature integrin
      subunits were sensitive to endoglycosidase H digestion and the inhibition could
      be mimicked in adherent cells by treatment with 1-deoxymannojirimycin. In 1
      deoxymannojirimycin-treated adherent keratinocytes, immature integrin subunits
      reached the cell surface; however, in keratinocytes induced to differentiate in
      suspension, no beta 1-integrin precursors were detected on the cell surface. Thus
      commitment to terminal differentiation results in a block both in integrin
      glycosylation and transport to the cell surface; down-regulation of receptor
      function must therefore involve modulation of pre-existing receptor on the cell
      surface. Although fibronectin or rabbit antiserum to alpha 5 beta 1 can inhibit
      suspension-induced terminal differentiation they did not overcome the inhibition
      of glycosylation. Nuclear run-on assays showed that transcription of the alpha 5
      and beta 1 genes was switched off during suspension-induced terminal
      differentiation, and treatment of adherent keratinocytes with actinomycin D
      suggested that the half-lives of the alpha 5 and beta 1 mRNAs were similar in
      adherent and suspended cells. Thus, loss of alpha 5 beta 1 from the cell surface
      reflects both inhibition of transcription of the subunit genes and inhibition of
      maturation and intracellular transport of newly synthesized subunits.

PMID- 1378841
TI  - Sequence, structure, and expression of a wasp venom protein with a negatively
      charged signal peptide and a novel repeating internal structure.
AB  - An expression cDNA library prepared from mRNA from the venom gland of a parasitic
      wasp, Chelonus sp. near curvimaculatus, was screened with polyclonal antibodies
      against a 33-kDa venom protein from this wasp. Immunoreactive clones were
      sequenced, yielding a complete inferred sequence for a protein with an NH2
      terminus identical with that of the 33-kDa protein. The structure of the cDNA
      showed an apparent encoded signal peptide, which was unusual in possessing 2
      glutamic acid residues juxtapositioned next to, or replacing, the conventional
      basic residues. The bulk of the mature protein sequence which follows the NH2
      terminal, 5000-kDa hydrophobic domain is composed of a dozen tandem repeats of a
      highly charged, approximately 14-residue sequence, except for the truncated
      eighth repeat which terminates in the only proline in this large domain. The
      primary structure is not closely related to any sequence in the GenBank data
      bank. Secondary structure analysis identified a turn occurring at or near each of
      12 invariantly conserved serine residues. Further, the codon used for this serine
      was invariant, whereas other serines in the protein (including a nearly invariant
      serine 2 residues away) used various codons. Results of epitope mapping
      experiments supported a proposed tertiary structure in which the NH2-terminal 5
      kDa forms a hydrophobic core, overlain with the charged repeats. Northern
      analysis of poly(A) RNA from the venom gland of young adult female wasps showed
      expression of a single 1-kilobase transcript, for which there is no corresponding
      message in normal or parasitized host larvae. The remarkable structure of this
      protein and structural data on other wasp venom proteins suggest an evolutionary
      pattern in which some proteins critical for venom function evolve by internal
      tandem duplication, and which are secreted after biosynthesis by a different
      mechanism from that used for proteins with classical signal peptides containing
      basic residues.

PMID- 1378842
TI  - The ES-242s, novel N-methyl-D-aspartate antagonists of microbial origin, interact
      with both the neurotransmitter recognition site and the ion channel domain.
AB  - ES-242-1 approximately 5 are novel microbial bioxanthracenes which do not contain
      nitrogen. The ES-242s inhibited the binding of [3H]TCP and [3H]CGS19755 to the N
      methyl-D-aspartate (NMDA) receptor complex. They had no effect on the binding of
      the specific ligands for the non-NMDA receptor. The biochemical and
      pharmacological properties of ES-242-1 were fully examined since it is the most
      potent of the five compounds. ES-242-1 is highly specific for the NMDA receptor;
      it has no effect on other receptors. Kinetic analyses indicated that ES-242-1
      inhibited the binding of [3H]TCP and [3H]CGS19755 in a competitive manner,
      respectively, suggesting that ES-242-1 interacts with both the transmitter
      recognition site and the channel domain. ES-242-1 selectively inhibited NMDA
      induced Ca2+ influx in primary cultures of mouse hippocampal neurons. ES-242-1
      also specifically blocked the increase in cyclic GMP accumulation induced by NMDA
      or L-glutamate in rat cerebellar slices. In a concentration range of 0.1-1.0
      microM, ES-242-1 was as potent as MK-801 in preventing glutamate-induced
      neurotoxicity in primary cultures of mouse hippocampal neurons. These results
      show that ES-242-1 is a potent and specific antagonist for the NMDA receptor. The
      antagonistic properties of the ES-242s appear to be due to a novel mechanism of
      action at the NMDA receptor.

PMID- 1378843
TI  - Cloning and expression of a cell surface receptor for advanced glycosylation end
      products of proteins.
AB  - Advanced glycosylation end products of proteins (AGEs) are nonenzymatically
      glycosylated proteins which accumulate in vascular tissue in aging and at an
      accelerated rate in diabetes. A approximately 35-kDa polypeptide with a unique
      NH2-terminal sequence has been isolated from bovine lung and found to be present
      on the surface of endothelial cells where it mediates the binding of AGEs
      (receptor for advanced glycosylation end product or RAGE). Using an
      oligonucleotide probe based on the amino-terminal sequence of RAGE, an apparently
      full-length cDNA of 1.5 kilobases was isolated from a bovine lung cDNA library.
      This cDNA encoded a 394 amino acid mature protein comprised of the following
      putative domains: an extracellular domain of 332 amino acids, a single
      hydrophobic membrane spanning domain of 19 amino acids, and a carboxyl-terminal
      domain of 43 amino acids. A partial clone encoding the human counterpart of RAGE,
      isolated from a human lung library, was found to be approximately 90% homologous
      to the bovine molecule. Based on computer analysis of the amino acid sequence of
      RAGE and comparison with databases, RAGE is a new member of the immunoglobulin
      superfamily of cell surface molecules and shares significant homology with MUC
      18, NCAM, and the cytoplasmic domain of CD20. Expression of the RAGE cDNA in 293
      cells allowed them to bind 125I-AGE-albumin in a saturable and dose-dependent
      manner (Kd approximately 100 nM), blocked by antibody to RAGE. Western blots of
      293 cells transfected with RAGE cDNA probed with anti-RAGE IgG demonstrated
      expression of immunoreactive protein compared to its absence in mock-transfected
      cells. These results suggest that RAGE functions as a cell surface receptor for
      AGEs, which could potentially mediate cellular effects of this class of
      glycosylated proteins.

PMID- 1378844
TI  - Specificity of human immunodeficiency virus-1 reverse transcriptase-associated
      ribonuclease H in removal of the minus-strand primer, tRNA(Lys3).
AB  - We have examined the specificity of human immunodeficiency virus-1 (HIV-1)
      reverse transcriptase-associated RNase H in removing the tRNA(Lys3) (-)-strand
      primer in vitro using a model substrate. This substrate represents an
      intermediate in the reverse transcription process where the tRNA(Lys3) primer has
      not yet been removed after (+)-strand strong stop DNA synthesis. The substrate
      consists of an RNA oligonucleotide corresponding to the 3'-terminal 17
      nucleotides of the tRNA(Lys3) linked to U5 DNA and annealed to single-stranded
      DNA containing the U5 and the primer-binding site. Upon incubation with HIV-1
      reverse transcriptase p66/p51 heterodimer, the minus-strand DNA product resulting
      from RNase H cleavage retained the 3'-rA from the model tRNA primer. Changing the
      3'-terminal AMP of the model tRNA primer from rA to dA did not alter the RNase H
      cleavage site. Further, the retention of AMP was not dependent on recognition of
      adjacent U5 sequences or the CCA terminus of the model tRNA(Lys3). The synthetic
      RNA primer was released as an intact species by a single endonucleolytic cleavage
      5' of the rA. The cleavage patterns of Moloney murine leukemia virus and avian
      myoblastosis virus RNase H activities on the HIV-1 model substrate were more
      heterogeneous compared to HIV-1 RNase H. This specificity of HIV-1 RNase H would
      result in linear DNA molecules with a single rA at the U5 terminus and would
      provide two bases adjacent to the conserved CA dinucleotide to be cleaved away
      during the integration process.

PMID- 1378845
TI  - Characterization of an endogenous RNA transcript with homology to the antisense
      strand of the human c-myc gene.
AB  - In addition to being regulated by a complex array of cis- and trans-acting
      factors, c-myc protooncogene expression may be modulated by antisense RNA
      transcripts. Our previous studies have determined that depletion of intracellular
      polyamines by alpha-difluoromethylornithine results in a marked decrease in the
      transcription of the human c-myc gene. Because of reports that antisense
      transcription occurs in the 5' and 3' regions of this gene, we used a genomic
      clone of the human c-myc gene to ascertain whether polyamine depletion might
      induce an antisense RNA transcript. These studies demonstrate that polyamine
      depletion of the human colon cancer cell line COLO 320 results in induction of an
      endogenous RNA transcript with high homology to the antisense strand of the
      second intervening sequence (PvuII-RsaI) of the c-myc gene. Furthermore, during
      such depletion, steady state levels of this transcript vary inversely to the
      sense direction c-myc RNA. RNase protection studies suggest that the antisense
      transcript may arise from a different gene locus than the c-myc gene. To further
      identify the origins of this RNA, a cDNA library was generated from size-selected
      RNA and screened with c-myc sequences. A 438-base pair cDNA was isolated with
      approximately 85% homology, to a 285-base region in the second intron of the c
      myc gene. Computer homology analysis further reveals that a 120-base region
      within this cDNA also has approximately 85% homology to the antisense strands of
      a number of genes, including the growth-related genes, N-myc, p53, and thymidine
      kinase. These studies provide the initial characterization of an endogenous
      antisense RNA transcript which could influence cell growth by modulating the
      expression of c-myc and other genes.

PMID- 1378846
TI  - Cloning of the mouse endothelial selectins. Expression of both E- and P-selectin
      is inducible by tumor necrosis factor alpha.
AB  - E-selectin (ELAM-1) and P-selectin (GMP-140, PADGEM, CD62) have both been
      described as human endothelial cell adhesion molecules for neutrophils and
      monocytes. Cell surface appearance of these two proteins on human umbilical vein
      endothelial cells can be regulated by different mechanisms: E-selectin is
      transcriptionally induced, within hours, by tumor necrosis factor alpha (TNF
      alpha) while P-selectin is transported from storage granules to the plasma
      membrane within minutes upon induction by various stimulating agents. We have
      obtained cDNA clones covering the full-length coding sequence of the homologous
      mouse proteins for both endothelial selectins. We show that synthesis of mouse P
      selectin, like that of E-selectin, is transiently induced by TNF-alpha in several
      endothelioma cell lines derived from different mouse tissues. This induction was
      monitored on both the RNA as well as the protein level. The TNF induced, newly
      synthesized P-selectin protein was detected on the cell surface. Protein
      expression of P-selectin increased with a slightly lower rate than expression of
      E-selectin. In organ cultures of lung tissue from TNF-injected mice, the
      synthesis of P-selectin was clearly elevated compared to control mice. The bovine
      P-selectin homolog recognized by cross-reaction with anti-mouse P-selectin
      antibodies was also TNF-inducible in primary capillary endothelial cells from
      adrenal cortex and in aorta-derived endothelial cells. Thus, P-selectin can be
      regulated on two different levels. While the transport of stored P-selectin to
      the cell surface is controlled by regulated secretion of storage granules, the
      synthesis and surface expression can be induced by TNF-alpha similarly to that of
      E-selectin.

PMID- 1378847
TI  - Autistic social dysfunction: some limitations of the theory of mind hypothesis.
AB  - This study examined the extent to which the social disabilities found in autism
      can be accounted for by the "Theory of Mind" hypothesis. Items related to social
      development from the Vineland Adaptive Behavior Scales were administered to 29 CA
      , MA- and IQ-matched pairs of young autistic and non-autistic, developmentally
      disabled children. These items were evaluated in relation to expected ages of
      acquisition based on the Vineland standardization database. Our results indicate
      that the social dysfunction in autism affects very basic and early emerging
      social behaviors which are typically present prior to the time at which even the
      earliest precursors of a theory of mind apparently emerge.

PMID- 1378848
TI  - "Theory of mind" in Asperger's syndrome.
AB  - Two studies are reported in which the ability of people with Asperger's syndrome
      to understand problems of the type "Peter thinks that Jane thinks that ..."
      tested. The results showed that in contrast to younger or more handicapped
      autistic individuals, Asperger subjects were able to solve problems of the type
      just outlined, i.e. that they possessed a second-order theory of mind. When asked
      to explain their solutions however, they typically did not use mental state terms
      but did not differ in this respect either from non-handicapped or socially
      impaired, chronic schizophrenic controls. The implications of the results for
      current cognitive theories of autistic impairment are discussed.

PMID- 1378849
TI  - Reaction time and movement time in children with a Developmental Coordination
      Disorder.
AB  - The Test of Motor Impairment (TOMI) was used to select 12 children with a
      Developmental Coordination Disorder (DCD) and 12 age-matched controls. In an
      aiming task, movement latency, movement duration and its variability were
      significantly prolonged in the DCD group. In a coincidence timing version of the
      task, absolute timing error was significantly greater in the DCD group. The most
      robust chronometric effect for differentiating the two groups seemed to be the
      duration of movement when the target was small. Multiple regression showed that
      TOMI was a powerful indicator of movement duration.

PMID- 1378850
TI  - Evaluation of viral-lysate enzyme-linked immunosorbent assay kits for detecting
      human immunodeficiency virus (type 1) infections using human sera standardized by
      quantitative western blotting.
AB  - The first generation of proprietary reagents for detecting antibodies to the
      Human Immunodeficiency Virus Type 1 (HIV-1) by enzyme-linked immunosorbent assay
      (ELISA) used as antigen partially purified virus from cell culture lysates. These
      tests, which are still in use, may vary in their antibody measurement
      capabilities if different proportions of the viral polypeptides are present in
      the viral lysate mixtures. We determined the quantities of antibodies in the
      serum of persons infected with HIV-1 by dilution analysis using 3 ELISA kits:
      Abbott [A], Du Pont [D], Genetic Systems [G]. The proportionate antibody titres
      of each serum to p24gag and gp160env/120env were established by quantitative
      Western blotting. Serum antibody titres were high, frequently over 1:10,000, a
      result observed both by ELISA and Western blot. For Kit D, sera with high
      proportions of antibody to p24gag produced antibody titration curves with steep
      slopes whereas shallower slopes were found in sera with high proportions of
      antibody to gp160env. In contrast, Kit A gave steeper slopes with sera enriched
      for gp160env antibodies. Kit G gave results with slopes intermediate between Kits
      A and D. Serum antibody titres differed between kits depending upon the
      proportion and concentration of antibodies in a given serum to gp160env and
      p24gag. The findings that both the concentration and proportion of antibodies to
      specific viral polypeptides in human sera markedly affect the signal intensity
      produced by proprietary ELISAs suggest the need for several control sera which
      reflect the diversity of human serum responses. Standardization of human
      reference sera by quantitative Western blotting will assist in evaluation and
      quality control of ELISA tests.

PMID- 1378851
TI  - A new electron microscope positive staining method for viruses in suspension.
AB  - A new procedure for the positive staining of viruses in suspension, the Tokuyasu
      staining procedure (TSP), was evaluated using a non-enveloped virus, rotavirus;
      an enveloped virus, rubella virus and two glutaraldehyde-treated enveloped
      viruses, Human T Cell Lymphotropic Virus Type I (HTLV-I) and Human
      Immunodeficiency Virus Type 1 (HIV-1) as models. The TSP involves an initial
      staining of the virus with uranyl acetate (UA) followed by thin embedding in a
      mixture of UA and polyvinyl alcohol (PVA). Using aqueous UA for the TSP, a
      combination of positively and negatively stained particles was seen for both
      rotavirus and rubella virus. With glutaraldehyde-fixed HTLV-I and HIV-1, stain
      penetration did not occur and only negative staining was observed. The
      substitution of methanolic UA for aqueous UA in the TSP resulted in only positive
      staining of rotavirus and rubella virus. The change in procedure also resulted in
      stain penetration of the glutaraldehyde-fixed HTLV-I and HIV-1 to give positively
      stained particles. Some novel morphological features of rotavirus and rubella
      virus structure were observed by the TSP.

PMID- 1378852
TI  - Autoantibodies associated with lupus induced by diverse drugs target a similar
      epitope in the (H2A-H2B)-DNA complex.
AB  - IgG reactivity with the (H2A-H2B)-DNA complex, a subunit of the nucleosome, has
      been detected in many patients with lupus induced by procainamide and quinidine,
      but the similarity among the epitopes targeted by these antibodies in this
      heterogeneous patient group as well as the prevalence of this specificity in
      lupus induced by other drugs is unknown. Studies with histone-DNA complexes
      formed by sequential addition on a solid phase demonstrated that complexes
      containing single histones had negligible antigenicity, indicating that DNA
      stabilizes a protein epitope in the H2A-H2B dimer or that the complete epitope is
      generated by a surface feature involving H2A-H2B and DNA. F(ab')2 isolated from a
      patient with procainamide-induced lupus blocked greater than 90% of the anti
      [(H2A-H2B)-DNA] reactivity in six of six sera from patients with lupus induced by
      procainamide, four of four quinidine-induced patients and in sera from patients
      with lupus induced by acebutolol, penicillamine, and isoniazid, but not
      methyldopa or auto-antibodies to the component macromolecules. Fab fragments
      purified from the IgG of two quinidine-induced lupus patients and patients with
      isoniazid- and procainamide-induced lupus retained 39% +/- 8% of their original
      IgG reactivity compared to 34 +/- 28% of the original anti-tetanus toxoid
      activity of Fab fragments in two of the same sera and two normal sera. These
      results indicate that anti-[(H2A-H2B)-DNA] does not require divalent antigen
      antibody complexes for stability, and that the complete epitope is created by the
      monomeric, trimolecular histone-DNA complex. We conclude that despite their
      pharmacologic and chemical heterogeneity, many lupus-inducing drugs elicit near
      identical autoantibodies.

PMID- 1378853
TI  - Integrin adhesion molecules in the human endometrium. Correlation with the normal
      and abnormal menstrual cycle.
AB  - Integrins are a class of cell adhesion molecules that participate in cell-cell
      and cell-substratum interactions and are present on essentially all human cells.
      The distribution of nine different alpha and beta integrin subunits in human
      endometrial tissue at different stages of the menstrual cycle was determined
      using immunoperoxidase staining. Glandular epithelial cells expressed primarily
      alpha 2, alpha 3, and alpha 6 (collagen/laminin receptors), while stromal cells
      expressed predominantly alpha 5 (fibronectin receptor). The presence of alpha 1
      on glandular epithelial cells was cycle specific, found only during the secretory
      phase. Expression of both subunits of the vitronectin receptor, alpha v beta 3,
      also underwent cycle specific changes on endometrial epithelial cells.
      Immunostaining for alpha v increased throughout the menstrual cycle, while the
      beta 3 subunit appeared abruptly on cycle day 20 on luminal as well as glandular
      epithelial cells. Discordant luteal phase biopsies (greater than or equal to 3 d
      "out of phase") from infertility patients exhibited delayed epithelial beta 3
      immunostaining. These results demonstrate similarities, as well as specific
      differences, between endometrium and other epithelial tissues. Certain integrin
      moieties appear to be regulated within the cycling endometrium and disruption of
      integrin expression may be associated with decreased uterine receptivity and
      infertility.

PMID- 1378855
TI  - Human hematopoietic stem cell adherence to cytokines and matrix molecules.
AB  - The hematopoietic microenvironment is a complex structure in which stem cells,
      progenitor cells, stromal cells, growth factors, and extracellular matrix (ECM)
      molecules each interact to direct the coordinate regulation of blood cell
      development. While much is known concerning the individual components of this
      microenvironment, little is understood of the interactions among these various
      components or, in particular, the nature of those interactions responsible for
      the regional localization of specific developmental signals. We hypothesized that
      cytokines act together with ECM molecules to anchor stem cells within the
      microenvironment, thus modulating their function. In order to analyze matrix
      cytokine-stem cell interactions, we developed an ECM model system in which
      purified stem cell populations and plastic-immobilized individual proteins are
      used to assess the role of various matrix molecules and/or cytokines in human
      hematopoietic cell development. Analysis of these interactions revealed that a
      single ECM protein, thrombospondin, in conjunction with a single cytokine (e.g.,
      c-kit ligand), constitutes a developmental signal that synergistically modulates
      hematopoietic stem cell function.

PMID- 1378854
TI  - The B7/BB1 antigen provides one of several costimulatory signals for the
      activation of CD4+ T lymphocytes by human blood dendritic cells in vitro.
AB  - T cells respond to peptide antigen in association with MHC products on antigen
      presenting cells (APCs). A number of accessory or costimulatory molecules have
      been identified that also contribute to T cell activation. Several of the known
      accessory molecules are expressed by freshly isolated dendritic cells, a
      distinctive leukocyte that is the most potent APC for the initiation of primary T
      cell responses. These include ICAM-1 (CD54), LFA-3 (CD58), and class I and II MHC
      products. Dendritic cells also constitutively express the accessory ligand for
      CD28, B7/BB1, which has not been previously identified on circulating leukocytes
      freshly isolated from peripheral blood. Dendritic cell expression of both B7/BB1
      and ICAM-1 (CD54) increases after binding to allogeneic T cells. Individual mAbs
      against several of the respective accessory T cell receptors, e.g., anti-CD2,
      anti-CD4, anti-CD11a, and anti-CD28, inhibit T cell proliferation in the
      dendritic cell-stimulated allogeneic mixed leukocyte reaction (MLR) by 40-70%.
      Combinations of these mAbs are synergistic in achieving near total inhibition.
      Other T cell-reactive mAbs, e.g., anti-CD5 and anti-CD45, are not inhibitory.
      Lymphokine secretion and blast transformation are similarly reduced when active
      accessory ligand-receptor interactions are blocked in the dendritic cell
      stimulated allogeneic MLR. Dendritic cells are unusual in their comparably higher
      expression of accessory ligands, among which B7/BB1 can now be included. These
      are pertinent to the efficiency with which dendritic cells in small numbers
      elicit strong primary T cell proliferative and effector responses.

PMID- 1378856
TI  - Stimulus-dependent secretion of plasma proteins from human neutrophils.
AB  - In search for matrix proteins released from secretory vesicles of human
      neutrophils, a prominent 67-kD protein was identified in the extracellular medium
      of neutrophils stimulated by the chemotactic peptide, FMLP. The protein was
      purified to apparent homogeneity and partially sequenced. The sequence of the
      first 32 NH2-terminal amino acids was identical to the sequence of albumin. mRNA
      for human albumin could not be detected in bone marrow cells, nor could
      biosynthetic labeling of albumin be demonstrated in bone marrow cells during
      incubation with [14C]leucine. Immunofluorescence studies on single cells
      demonstrated the presence of intracellular albumin in fixed permeabilized
      neutrophils. Light microscopy of immunogold-silver-stained cryosections
      visualized albumin in cytoplasmic "granules." The morphology of these was
      determined by immunoelectron microscopy as vesicles of varying form and size.
      Subcellular fractionation studies on unstimulated neutrophils demonstrated the
      presence of albumin in the low density pre-gamma and gamma-regions that contain
      secretory vesicles, but are devoid of specific granules and azurophil granules.
      Albumin was readily released from these structures during activation of
      neutrophils with inflammatory mediators. Immunoblotting demonstrated the presence
      of immunoglobulin and transferrin along with albumin in exocytosed material from
      stimulated neutrophils. This indicates that secretory vesicles are unique
      endocytic vesicles that can be triggered to exocytose by inflammatory stimuli.

PMID- 1378857
TI  - Hemopoietic growth factors: a review.
AB  - The hemopoietic growth factors are peptide hormones that are known to be
      responsible for the in vitro and in vivo proliferation of bone marrow progenitor
      cells into mature differentiated cells. These cytokines have had a major impact
      on the management of patients with cytopenias and have been extensively used as
      an adjunct to the management of patients with hematologic malignancies, with or
      without prior intensive chemotherapy. Other potential uses, being rigorously
      studied, include the potential mobilization of stem cells as well as recruitment
      phase-specific cells into the cell cycle, thus providing a more sensitive
      environment for targeting specific chemotherapeutic agents.

PMID- 1378858
TI  - Prognostic significance of ventricular premature depolarizations measured 1 year
      after myocardial infarction in patients with early postinfarction asymptomatic
      ventricular arrhythmia.
AB  - OBJECTIVES: The objective of this study was to examine the relation between death
      and the frequency of premature ventricular depolarizations measured approximately
      1 year after myocardial infarction. BACKGROUND: The reported association between
      premature ventricular depolarizations and death in the weeks after myocardial
      infarction is in part the basis for the use of antiarrhythmic drugs. Such an
      association has not been reported on for observations obtained at a much greater
      interval after myocardial infarction. METHODS: We examined the association
      between mortality and premature ventricular depolarization rates measured 1 year
      after myocardial infarction in patients with asymptomatic ventricular arrhythmia
      early (between 6 and 90 days, median 28) after infarction, as measured by 24-h
      ambulatory electrocardiographic recording. The study group consisted of 502
      patients enrolled in the Cardiac Arrhythmia Pilot Study during 1983 to 1985. They
      were followed up during the course of the study and subsequently by a National
      Death Index search (average follow-up interval 1,080 days). RESULTS: Death was
      recorded for 87 patients through 1987. Because patients were admitted to the
      Cardiac Arrhythmia Pilot Study only if they had greater than or equal to 10
      ventricular premature depolarizations/h, the arrhythmia rate measured at baseline
      (that is, early after infarction) was not expected to, and did not, predict
      mortality. In 360 patients ventricular premature depolarization rates were
      measured approximately 1 year from their index myocardial infarction while they
      were not receiving antiarrhythmic therapy. In these patients, who had survived 1
      year after the index infarction, the rate of ventricular premature
      depolarizations/h measured 1 year after infarction was highly predictive of
      subsequent death (p less than 0.001). Recent heart failure and a history of
      diabetes mellitus were also strongly predictive of death. CONCLUSION: The
      prognostic value of ventricular premature depolarizations observed 1 year after a
      myocardial infarction may be significant even in a sample selected for frequent
      ventricular premature depolarizations observed early after the event.

PMID- 1378859
TI  - Cardiomyopathy and myocarditis in children with ventricular ectopic rhythm.
AB  - OBJECTIVE: The objective of this study was to evaluate the histologic features of
      the myocardium in children with abnormal ventricular ectopic rhythm but a
      structurally normal heart. BACKGROUND: Abnormal ventricular ectopic rhythm in
      children with a structurally normal heart is an uncommon but serious condition.
      Previous studies in adults with these findings have shown that approximately 10%
      have "primary electrical disease" and that 40% to 100% of these have abnormal
      histologic findings. METHODS: Endomyocardial biopsy samples were obtained
      prospectively in 33 subjects presenting with ventricular ectopic rhythm but a
      structurally normal heart by physical examination and noninvasive studies. Biopsy
      specimens were evaluated for histologic changes consistent with dilated
      cardiomyopathy or myocarditis and these results were compared with noninvasive
      and invasive clinical findings. RESULTS: Of the 33 subjects, 16 (48%) had normal
      myocardial histologic features (Group A), 14 (42%) had changes similar to the
      histologic features seen with idiopathic dilated cardiomyopathy (Group B) and 3
      (9%) had lymphocytic myocarditis (Group C). Presenting clinical symptoms, surface
      electrocardiograms (ECGs), exercise stress testing and electrophysiologic
      stimulation tests failed to predict the biopsy results. Twenty-four-hour
      ambulatory ECGs showed a statistical difference between sustained and
      nonsustained ventricular tachycardia in Group A versus Group B (p less than
      0.007), with Group A having more sustained ventricular tachycardia. Left
      ventricular function measured by fractional shortening on echocardiography did
      not differ between groups, but left ventricular end-diastolic dimension was
      greater in the subjects with abnormal histologic findings (Group B) (p less than
      0.03). CONCLUSIONS: These results provide evidence that approximately 50% of
      children with abnormal ventricular ectopic rhythm but a structurally normal heart
      may have subclinical cardiomyopathy or unsuspected myocarditis.

PMID- 1378860
TI  - Effective interventions for reading disability.
AB  - A simple, readily accessible, and inexpensive intervention which produces
      immediate improvements in the reading comprehension abilities of reading-disabled
      children has been found. The intervention consists of colored overlays, or
      overlays which reduce the contrast of printed materials. This intervention
      produces reading comprehension gains in approximately 80 percent of the reading
      disabled children tested.

PMID- 1378861
TI  - Certain inhibitors of protein serine/threonine kinases also inhibit tyrosine
      phosphorylation of phospholipase C gamma 1 and other proteins and reveal distinct
      roles for tyrosine kinase(s) and protein kinase C in stimulated, rat basophilic
      RBL-2H3 cells.
AB  - Various inhibitors of phospholipases and serine/threonine kinases were used to
      determine whether activation of these enzymes was necessary for Ag-induced
      exocytosis in rat basophilic RBL-2H3 cells. Several inhibitors, however,
      inhibited events other than those intended in stimulated RBL-2H3 cells.
      Staurosporine and KT5926, inhibitors of protein kinase C and myosin L chain
      kinase, respectively, suppressed, in a dose-dependent manner, hydrolysis of
      inositol phospholipids, release of arachidonic acid, and exocytosis in cells
      stimulated with Ag or Ca(2+)-ionophore, A23187. Such generalized inhibition could
      also be induced in permeabilized cells with several peptide inhibitors of
      tyrosine kinases. All the above inhibitors suppressed Ag-induced tyrosine
      phosphorylation of several proteins, including phospholipase C gamma 1, and this
      suppression correlated with the inhibition of hydrolysis of inositol
      phospholipids and exocytosis. Three inhibitors of protein kinase C, Ro31-7549,
      calphostin C, and a peptide inhibitor, did not inhibit the tyrosine
      phosphorylation of proteins but selectively blocked exocytosis, presumably, by
      inhibiting protein kinase C. Thus, both tyrosine phosphorylation of proteins and
      the activation of protein kinase C were necessary events for hydrolysis of
      inositol phospholipids and exocytosis.

PMID- 1378862
TI  - Identification of a thyroiditogenic sequence within the thyroglobulin molecule.
AB  - Thyroglobulin (Tg)-specific T cells are important in the induction of
      experimental autoimmune thyroiditis (EAT), but the nature and the number of the
      Tg T cell epitopes involved in the disease process are unknown. Through the use
      of computerized algorithms that search for putative T cell epitopes, a 17-mer
      peptide (TgP1) was identified within the known portion of the rat Tg sequence
      (corresponding to amino acids 2495 to 2511 of the human Tg sequence) that induced
      strong mononuclear cell infiltration of the thyroid in classic EAT-susceptible
      murine strains such as SJL, C3H, and B10.BR and low or undetectable infiltration
      in EAT-resistant strains such as BALB/c and B10. TgP1 appears to be
      phylogenetically conserved since it is completely homologous to its bovine
      counterpart and differs at a single amino acid position from its human analogue.
      After priming with TgP1 in vivo, significant proliferative T cell responses to
      TgP1 in vitro were observed only with lymphocytes from susceptible (high
      responder) strains, thus correlating proliferative capacity with EAT induction.
      TgP1-primed T cells did not respond to intact mouse Tg (MTg) or rat Tg in vitro
      and, conversely, T cells primed in vivo with MTg or rat Tg did not respond to
      TgP1 in culture, suggesting that TgP1 is comprised of non-immunodominant T cell
      determinants. TgP1 was defined as a serologically nonimmunodominant epitope as
      well, since in vivo priming of all strains with MTg led to strong MTg-specific
      IgG responses but no TgP1-specific responses in ELISA assays. This was not due to
      lack of immunogenic B cell determinants on TgP1, however, because peptide
      challenge of EAT-susceptible strains elicited TgP1-specific IgG that also cross
      reacted with MTg and rat, human, bovine, and porcine Tg. The data demonstrate
      that TgP1 delineates nonimmunodominant but highly immunogenic determinants at
      both the T and B cell level, which may play an important role in the development
      of autoimmune thyroiditis.

PMID- 1378863
TI  - Evidence for the existence of two parallel differentiation pathways in the thymus
      of MRL lpr/lpr mice.
AB  - MRL mice homozygous for the lpr/lpr gene develop a massive lymphadenopathy caused
      by the accumulation of CD4-CD8-, Thy-1-positive T cells that express B220. This
      phenotypically unusual T cell population coexists with normal, B220- T cells in
      lpr/lpr animals. To investigate the origin and differentiation pathway of B220+ T
      cells, the expression of a panel of developmentally regulated cell surface
      markers including TCR, CD4, CD8, Thy-1, and B220 was examined. Thymocytes and
      peripheral T lymphocytes from lpr/lpr mice were analyzed by four-color flow
      cytometry. The results showed that both B220+ and B220- thymocytes contained all
      of CD4-CD8-, CD4+CD8+, and CD4 or CD8 single positive T cell subpopulation in the
      lpr thymus. Expression of the V beta 11 TCR, measured by flow cytometry and
      reverse polymerase chain reaction, was demonstrated in lpr thymus. However, the
      number of T cells expressing V beta 11 was greatly reduced in both the B220+ and
      B220- T cell populations in lymph node, spleen, and liver. Taken together, the
      data provide evidence for maturation and selection of a distinct population of
      B220+ T cells in the thymus of MRL lpr/lpr mice.

PMID- 1378864
TI  - Rheumatoid factors from patients with rheumatoid arthritis react with beta 2
      microglobulin.
AB  - IgM rheumatoid factors (RF) from 18 sera of rheumatoid arthritis (RA) patients
      isolated from monomeric IgG affinity columns showed strongly positive ELISA
      reactions with human beta 2-microglobulin (beta 2m), as well as with recombinant
      beta 2m. When the same RA sera were adsorbed to beta 2m-Sepharose affinity
      columns, eluted material showed predominant IgM anti-Fc of IgG and anti-beta 2m
      reactivity. Inhibition reactions with "RF" obtained from IgG affinity columns
      showed slightly higher reactivity of RF for Fc over beta 2m; however, when RF
      from the same RA serum had been adsorbed to and eluted from beta 2m affinity
      columns, beta 2m showed greater inhibition than Fc for RF reacting with either
      beta 2m or Fc on ELISA plates. Thus two overlapping populations of RF were
      identified in RA sera showing reactivity with both beta 2m and Fc of IgG. When RF
      were isolated from IgG columns, affinity was slightly higher for Fc than beta 2m.
      Conversely, RF eluted from beta 2m Sepharose reacted slightly more with beta 2 m
      than Fc. Trypsin digests of a polyclonal RA IgM RF showed no beta 2m reactivity
      in Fc mu 5 fragments. Fab mu RF retained slight anti-Fc IgG but no residual anti
      beta 2m activity. Monoclonal human IgM, IgG, or IgA RF either from mixed
      cryoglobulins or EBV-stimulated RA lymphoid cell lines showed negative or
      occasional weakly positive anti-beta 2m activity. Overlapping 7-mer peptide ELISA
      analysis of the entire 99-amino acid sequence of beta 2m showed a major RF
      reactive linear hydrophilic sequence at positions 56-60 which included a 3-amino
      acid exact homology to positions 401, 403, and 404 of the C gamma 3 domain. A
      peptide encompassing this sequence produced 90% inhibition of RF binding to whole
      beta 2m. Substitution of neutral glycines for each amino acid throughout the
      reactive epitope at positions 56-66 indicated that lysine at position 58 aspartic
      acid at 59, and tryptophane at 60 represented major portions of the RF-reactive
      epitope. These findings indicate that human RF derived from patients with RA
      react with other epitopes besides those present on IgG Fc, including epitopes on
      human beta 2m. For many years serum RF3 found in patients with RA have been
      regarded as premier examples of autoantibodies to autologous IgG.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1378865
TI  - CD40 is functionally expressed on human thymic epithelial cells.
AB  - CD40 is a prominent B cell Ag also found on certain epithelial cells and on
      carcinomas. In this report, we analyzed CD40 distribution in the human thymus.
      CD40 was not found on the majority of CD45-positive thymocytes, but was present
      in a CD45-negative stromal cell population. Immunohistology showed CD40
      expression on cortical thymic epithelial cells (TEC), medullary TEC, thymic
      interdigitating cells, and thymic B cells. CD40 was not found on thymocytes,
      endothelial cells, or on the fibroblasts of the septae. Expression of CD40 was
      specifically maintained on cultured TEC and not found on cultured thymic
      fibroblasts. IL-1 alpha, TNF-alpha, IFN-gamma, but not IL-4, significantly up
      regulated the membrane expression of CD40 on cultured TEC. The regulation of CD40
      was similar to that of ICAM-1, and contrasted with that of MHC class II Ag, which
      could only be induced by IFN-gamma but not by IL-1, TNF, or IL-4. Northern blot
      analysis showed the presence of a 1.4-kb mRNA transcript for CD40 in TEC, which
      was up-regulated by IL-1 and IFN-gamma. Cross-linking of CD40 at the surface of
      human TEC in the absence of IL-1 stimulation failed to induce cytokine secretion.
      Triggering of TEC with anti-CD40 mAb in conjunction with IFN-gamma and IL-1
      stimulation increased granulocyte-macrophage CSF secretion in a dose-dependent
      manner. The effect was visible as early as 24 h after triggering, occurred in the
      absence of cellular proliferation, and was specific for CD40 since triggering of
      other TEC membrane Ag such as ICAM-1 or MHC class I molecules had no effect to
      increase cytokine production in TEC. These data demonstrate that CD40 is
      expressed and is a functional molecule at the surface of the epithelial cells of
      the thymus.

PMID- 1378866
TI  - Identification and characterization of a second encephalitogenic determinant of
      myelin proteolipid protein (residues 178-191) for SJL mice.
AB  - We previously described a synthetic peptide of myelin proteolipid protein (PLP),
      peptide 139-151, which induces experimental allergic encephalomyelitis in SJL/J
      (H-2s) mice. We have now identified an additional determinant, PLP residues 178
      191, that is also a potent encephalitogen in this strain. When PLP peptide 178
      191 was compared with peptide 139-151 on an equimolar basis, the day of onset of
      disease induced by PLP 178-191 was earlier, but the incidence, severity, and
      histologic features were indistinguishable. Lymph node cells from animals
      immunized with the whole PLP molecule responded to both PLP 178-191 and 139-151,
      suggesting immunologic codominance of the two epitopes. PLP 178-191 elicited
      stronger proliferative responses and this may relate to the earlier onset of
      disease induced with this peptide. Two CD4+, peptide-specific, I-A(s)-restricted
      T cell lines, selected by stimulation of lymph node cells with either PLP 178-191
      or 139-151, were each encephalitogenic in naive syngeneic mice. The presence of
      multiple encephalitogenic codominant PLP epitopes within a single mouse strain
      emphasizes the complexity of the immune response to PLP and its potential as a
      target Ag in autoimmune demyelinating diseases.

PMID- 1378867
TI  - Role of I-A molecules in early stages of B cell maturation.
AB  - The role of the Ia molecule in the early phase of B cell development remains
      controversial. In contrast to previous studies, we have detected minute amounts
      of Ia (I-A) molecule on early B lineage (B220+IgM-) cells from normal bone
      marrow, using ELISA. The presence of the I-A molecule even on pro-B cells was
      deduced from experiments in which a monoclonal anti-I-A antibody completely
      blocked the generation of pre-B cells from B progenitor (B220-) cells in stromal
      cell-dependent B cell culture. Inasmuch as this antibody did not inhibit the
      maturation of pre-B cells to IgM+ B cells in culture, the I-A molecule on early B
      lineage cells probably plays a role in their maturation. We also examined the
      role of the I-A molecule in early B cell development, using transgenic mice
      harboring the antisense DNA to I-A beta-chain gene. The amount of I-A molecule on
      splenic B cells from the young transgenic mice decreased in the presence of
      abundant amounts of the antisense RNA. B cell development was perturbed in spleen
      from the transgenic mice. Stromal cell-dependent B cell cultures from these mice
      clearly showed that the maturation of B lineage cells was delayed at a very early
      stage of development (B220- to B220+). We propose that the I-A molecule on early
      B lineage cells may play an essential role in their maturation.

PMID- 1378868
TI  - Granulocyte colony-stimulating factor treatment protects rodents against
      lipopolysaccharide-induced toxicity via suppression of systemic tumor necrosis
      factor-alpha.
AB  - Pretreatment with recombinant human granulocyte CSF (G-CSF) protected mice in two
      different models of septic shock. Intravenous injection of 250 micrograms/kg G
      CSF to mice prevented lethality induced by 5 mg/kg LPS. Injection of 50
      micrograms/kg G-CSF protected galactosamine-sensitized mice against LPS-induced
      hepatitis. In either case, this protection was accompanied by a suppression of
      LPS-induced serum TNF activity. In contrast, when galactosamine-sensitized mice
      were pretreated with 50 micrograms/kg murine recombinant granulocyte/macrophage
      CSF instead of G-CSF and subsequently challenged with LPS, serum TNF activity was
      significantly enhanced and mortality was increased. The suppressive effect of G
      CSF on LPS-induced TNF production was also demonstrated in rats. In vivo, no TNF
      was detectable in the blood of LPS-treated rats, which had been pretreated with G
      CSF. Ex vivo, alveolar macrophages, bone marrow macrophages, Kupffer cells, or
      peritoneal macrophages prepared from G-CSF-treated rats produced significantly
      less TNF upon stimulation with LPS than corresponding populations from control
      rats. However, when these macrophage populations were incubated with G-CSF in
      vitro, LPS-induced TNF production was unaffected. These data suggest that the G
      CSF-mediated suppression of TNF production is not a direct effect of G-CSF on
      macrophages. To examine whether, independent of the protection against LPS, G-CSF
      treatment still activated neutrophils, it was demonstrated that granulocytes from
      G-CSF-treated rats were primed for PMA-induced oxidative burst and for
      ionophore/arachidonic acid-stimulated lipoxygenase product formation. The
      experiments of this study support the notion that G-CSF is a negative feedback
      signal for macrophage-derived TNF-alpha production during Gram-negative sepsis.

PMID- 1378869
TI  - Identification of new epitopes recognized by human monoclonal antibodies with
      neutralizing and antibody-dependent cellular cytotoxicity activities specific for
      human T cell leukemia virus type 1.
AB  - We have generated a number of EBV-transformed B cell lines producing human mAb
      against human T cell leukemia virus type 1 (HTLV-1) from the peripheral blood B
      lymphocytes obtained from patients with HTLV-1-associated myelopathy/tropical
      spastic paraparesis. Various synthetic peptides corresponding to antigenic
      regions of HTLV-1 gag and env proteins were used for the screening of antibodies
      in ELISA. In our study, four IgG mAb to the gag p19 amino acids 100 to 130, and 5
      IgG mAb to the env p46 amino acids 175 to 199 were characterized. An
      immunofluorescence assay showed that all of these mAb specifically bound to the
      surface of HTLV-1-bearing cell lines. Among these mAb, one anti-gp46 mAb,
      designated KE36-11, neutralized the infectivity of HTLV-1 as determined by both
      the inhibition of HTLV-1-induced syncytium formation and transformation assays in
      vitro. An antibody-binding assay using overlapping oligopeptides revealed that
      KE36-11 recognized a new epitope locating between the gp46 amino acid sequence
      187-193 (Ala-Pro-Pro-Leu-Leu-Pro-His). Another anti-gp46 mAb, designated KE36-7,
      showed antibody-dependent cellular cytotoxicity against HTLV-1-bearing cell line.
      KE36-7 bound strongly to the 10-mer peptide-gp46 187-196, and weakly to peptides
      containing the gp46 amino acid sequence 191-196 (Leu-Pro-His-Ser-Asn-Leu). These
      two epitopes, which are associated with HTLV-1 neutralization and antibody
      dependent cellular cytotoxicity, are thus the first epitopes identified in human
      HTLV-1 infection. It is possible that passive immunization of humans with these
      two human mAb are effective on the protection of HTLV-1 infection in vivo.

PMID- 1378870
TI  - Antigenic and genetic analyses of human rotaviruses in Chiang Mai, Thailand:
      evidence for a close relationship between human and animal rotaviruses.
AB  - Serotyping of group A rotaviruses obtained from stools of 158 diarrheic patients
      in Chiang Mai, Thailand, by ELISA with monoclonal antibodies revealed a yearly
      change in the prevalence of individual serotypes. Three unusual human rotavirus
      strains were isolated. Strain Mc35 had subgroup I-serotype 10 antigen and a long
      RNA electrophoretic type, a property hitherto found only in bovine rotaviruses.
      RNA-RNA hybridization tests showed that the strain is more closely related
      genetically to bovine than to human rotaviruses. Strain Mc323, although
      serologically closely related to serotype 9, had subgroup I specificity and a
      long RNA electrophoretic type, a characteristic common to nonhuman rotaviruses.
      Strain Mc345, with an aberrant RNA pattern possibly due to genome rearrangement,
      had the same antigenic specificity as Mc323. These 2 strains were genetically
      very closely related to each other and were more related to porcine than to human
      rotaviruses. These results provide insights into the evolutionary mechanisms of
      human rotaviruses.

PMID- 1378871
TI  - Human vaccination with Escherichia coli J5 mutant induces cross-reactive
      bactericidal antibody against Neisseria gonorrhoeae lipooligosaccharide.
AB  - The lipopolysaccharides of enteric gram-negative bacteria and the
      lipooligosaccharides (LOS) of Neisseria gonorrhoeae may share antigenic
      determinants that are targets of bactericidal antibody. Natural (disseminated)
      infection with a serum-resistant gonococcal strain and immunization with
      Escherichia coli J5 stimulated bactericidal IgG anti-LOS antibodies that
      recognize different serum-resistant gonococcal LOS epitopes. In bactericidal
      assays, convalescent serum from disseminated infection killed only the homologous
      strain while post-J5 vaccination serum killed 6 of 9 additional strains. Both
      convalescent and post-J5 vaccination sera mediated marker (51Cr) release from
      liposomes sensitized with serum-resistant gonococcal LOS (homologous strain),
      linking acquired killing activity to cross-reacting anti-LOS antibody. Post-J5
      IgG mediated 51Cr release more effectively than did convalescent IgG. Thus,
      bactericidal antibody elicited by J5 vaccination is more efficacious and broadly
      cross-reactive against serum-resistant gonococci than is antibody elicited by
      natural infection. Moreover, multiple LOS epitopes may serve as bactericidal
      targets on serum-resistant gonococci.

PMID- 1378872
TI  - Effect of granulocyte colony-stimulating factor on sepsis-induced changes in
      neutrophil accumulation and organ glucose uptake.
AB  - Neutropenia was seen in rats made septic by subcutaneous (sc) injection of
      Escherichia coli. The sepsis-induced increase in glucose uptake by tissues
      distant from the site of infection was not associated with increased
      myeloperoxidase (MPO) activity. Only the skin and muscle at the site of infection
      demonstrated an increase in both glucose uptake and MPO activity. Granulocyte
      colony-stimulating factor (G-CSF) attenuated the sepsis-induced decrease in
      circulating neutrophils. Both glucose uptake and MPO activity of skin and muscle
      adjacent to the infection site showed a smaller increase in G-CSF treated rats.
      In contrast, septic rats injected with G-CSF exhibited a greater number of
      leukocytes and a larger reduction in the number of bacteria in the sc lavage
      fluid. These results demonstrate that G-CSF is a potent immunomodulator that
      stimulates neutrophil function and also increases their recruitment to the site
      of infection, resulting in improved bacterial killing and host defense.

PMID- 1378873
TI  - Cytokine and acute-phase reactant levels in serum of children with cancer
      admitted for fever and neutropenia.
AB  - Serum concentrations of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)
      1 beta, IL-6, and the acute-phase reactants C-reactive protein (CRP) and serum
      amyloid A (SAA) were measured on admission in 46 neutropenic children with cancer
      in 81 episodes of fever. The aim was to find out whether any of these variables
      would differentiate true bacteremia from fever due to other causes. In most
      episodes serum concentrations of TNF alpha and IL-1 beta were elevated. IL-6 was
      detectable in 68%, but the serum concentration was elevated in only 15%. SAA
      proved to be more sensitive than CRP for the early detection of bacteremia.
      However, not even SAA was sufficiently accurate at the individual level. We
      conclude that the cytokine and acute-phase protein levels found were related to
      the febrile response but did not correlate with documented bacterial etiology.

PMID- 1378874
TI  - Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro
      sequence of the polymorphic epithelial mucin (PEM) protein core in breast
      carcinoma cells.
AB  - Epithelial mucins have obtained increasing clinical relevance since they were
      found in the serum of cancer patients and were shown to be elevated in metastatic
      disease. We report here the characterization of the monoclonal antibody (MAb) 436
      which recognises the protein core of the polymorphic epithelial mucin (PEM) of
      the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane
      enriched fractions prepared from metastatic lesions in the axillary lymph nodes.
      The antigenic determinant recognized by the MAb 436 is expressed on the surface
      of breast cancer cells and was measured by ELISA on all of 50 cytosol
      preparations of primary breast tumors. Immunohistochemistry showed 98% of primary
      and 100% of metastatic breast cancer lesions to be positive with the 436
      antigenic determinant expressed both in the cytoplasm and at the plasma membrane
      level of the tumor cells. Moreover, the antigen was expressed in a homogeneous
      fashion (80-100% of the total number of tumor cells) in more than 60% of the
      tumors. Reactivity with normal tissues was rare and scattered and restricted to
      glandular structures particularly at the luminal border level except for the
      distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436
      antigen distribution was observed. Other cancers proved positive but the
      reactivity was always variable and heterogeneous. The antigen recognized by MAb
      436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein
      resolved in two bands. Epitope mapping experiments using overlapping octapeptides
      in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence
      the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378875
TI  - Serum AFP, hCG and CEA in the management of patients with testicular, ovarian and
      extragonadal germ cell tumors.
AB  - Serum levels of AFP, hCG and CEA were initially and serially measured in 59
      patients with testicular germ cell tumors, and serially in 37 with ovarian and 3
      with extragonadal germ cell tumors. Patients with seminoma/dysgerminoma or mature
      teratoma had normal serum AFP and sporadically slightly elevated hCG. Some
      patients with embryonal carcinoma, pure or with admixture of seminoma, had serum
      AFP elevated to maximum 100 U/ml, yet its use for monitoring therapy was limited.
      Patients with yolk sac tumors had elevated AFP and sometimes CEA levels, those
      with choriocarcinoma had elevated hCG, and those with compound tumors had one or
      more of the markers highly elevated. High AFP and/or hCG levels indicated the
      presence of the relevant tumor cells both in the primary and in residual tumor
      and/or metastases, also those missed in histological material, and thus were
      useful in restaging. Unfortunately, their absence in serum did not exclude the
      presence of marker-negative subpopulations of tumor cells. Changes in marker
      values paralleled the effects of treatment: the level increasing from any nadir
      heralded recurrence in patients in remission; elevated or increasing levels
      during therapy implied resistance to the therapy; decreasing levels indicated
      regression even though a return to the normal range did not mean eradication of
      all tumor cells.

PMID- 1378876
TI  - Preliminary study of alpha-fetoprotein in nonmalignant liver diseases. A clinico
      biochemical evaluation.
AB  - This preliminary study was carried out to evaluate the behavior of AFP in 155
      patients with benign diffuse liver diseases who underwent thorough clinical and
      laboratory evaluation. We found correlations between AFP and some clinical and
      biochemical parameters characteristic of liver diseases; serum glutamic
      oxalacetic transaminase (GOT) proved the most relevant (r = 0.27 p = 0.0004) and
      most reliable marker to predict AFP levels. 22.6% of the patients as a whole,
      25.6% of the 86 cirrhotics and 18.8% of the 69 non-cirrhotics, had increased
      levels of AFP. Patients with active liver disease as measured by increased GOT,
      had higher AFP levels than patients with quiescent liver diseases (p = 0.0048),
      suggesting that cytolysis and/or regeneration plays a role in the increase in
      AFP. Elevation of the cut-off level was necessary to improve the specificity of
      AFP as a tumor marker. In our series, the cut-off of 9 ng/ml was exceeded by only
      10% of the patients.

PMID- 1378877
TI  - Follow-up of hepatitis C virus infection in chimpanzees: determination of
      viraemia and specific humoral immune response.
AB  - Chimpanzees were inoculated intravenously with the H strain of hepatitis C virus
      (HCV), and analysed for viraemia using the polymerase chain reaction and for a
      humoral immune response using first and second generation anti-HCV ELISAs and an
      immunoblot assay (4-RIBA). In all seven chimpanzees studied, viraemia occurred
      several weeks before a significant increase in serum alanine transferase (ALT)
      activity, whereas the first circulating anti-HCV antibodies became detectable at
      the time of significant increase in ALT levels, provided the second generation
      ELISA or 4-RIBA was used. On the basis of the duration of viraemia the
      chimpanzees studied could be assigned to two different groups: those in which
      viraemia disappeared in conjunction with or shortly after seroconversion, and
      those remaining viraemic for many weeks after the appearance of antibodies. The
      clearance of HCV from the circulation did not correlate with the antibody pattern
      determined using 4-RIBA, i.e. the HCV-specific assays currently available do not
      enable us to predict whether an infected chimpanzee will develop persistent
      viraemia. Only two of the seven chimpanzees analysed developed anti-core protein
      (c-22) antibodies, which appeared at the same time as the first ALT peak, whereas
      all animals developed antibodies to the non-structural protein, c-33, and these
      antibodies persisted.

PMID- 1378878
TI  - Assignment of mutant tsN19 (complementation group E) of respiratory syncytial
      virus to the P protein gene.
AB  - The mutation responsible for the temperature-sensitive (ts) phenotype of mutant
      tsN19 (complementation group E) of respiratory syncytial virus has been located
      to the P protein gene. Viral protein synthesis was completely restricted at 39
      degrees C, and the tsN19 P protein did not react with an anti-P monoclonal
      antibody (MAb) (3-5) at 33 degrees C. Reversion of temperature sensitivity
      restored reactivity with MAb 3-5. Nucleotide sequence determination and in vitro
      expression of cDNA clones of P mRNA derived from wild-type, tsN19 and non-ts
      revertant-infected cells, revealed that temperature sensitivity and loss of
      reactivity with MAb 3-5 were consequences of a Gly----Ser amino acid change at
      position 172. A low M(r) polypeptide, which represented the C-terminal 93 amino
      acids of the P protein, was produced by internal initiation in the P open reading
      frame during in vitro translation, and a similar product was detected transiently
      in vivo.

PMID- 1378879
TI  - Antigenic diversity of human parainfluenza virus type 1 isolates and their
      immunological relationship with Sendai virus revealed by using monoclonal
      antibodies.
AB  - Fifty-six monoclonal antibodies (MAbs) directed against human parainfluenza virus
      type 1 (hPIV-1) were prepared in order to identify the structural proteins of
      hPIV-1, to examine the immunological relationship between hPIV-1 and Sendai virus
      (SV), and to determine the antigenic diversity of clinical isolates of hPIV-1. In
      addition, 41 MAbs characterized previously and directed against SV were used for
      immunological comparison of SV and hPIV-1 isolates. Of the MAbs against hPIV-1,
      two reacted with phospho (P) protein, 11 with nucleocapsid protein (NP), 24 with
      haemagglutinin-neuraminidase (HN) protein and 19 with fusion (F) protein. With
      the aid of MAbs against hPIV-1 and those against SV showing cross-reactivity with
      hPIV-1, the structural proteins of hPIV-1 were identified; p83, p56, p34, gp74
      and gp60 of hPIV-1 were identified as the P, NP, M, HN and F proteins,
      respectively. The MAbs against the P protein and NP of hPIV-1 showed limited
      cross-reactivity with SV, whereas they had high reactivity with clinical isolates
      of hPIV-1. Interestingly, one MAb against the NP of hPIV-1 lacked reactivity with
      clinical isolates which were isolated in the 1970s and 1980s. The MAbs against
      the HN of hPIV-1 also exhibited quite limited reactivity with SV and the clinical
      isolates; two groups of HN-specific MAbs showed almost no reactivity with the
      clinical isolates from the 1970s and 1980s, similarly to the NP-specific MAb.
      However, anti-HN MAbs belonging to the two groups showing specific activities
      (neuraminidase inhibition and haemolysis inhibition) reacted with almost all
      clinical isolates. On the other hand, although anti-F protein MAbs had limited
      reactivity with SV, they showed reactivity with almost all hPIV-1 isolates. The
      MAbs against the P, NP, M, HN and F proteins of SV also showed limited cross
      reactivity with the clinical hPIV-1 isolates, and this reactivity was independent
      of the time and place of isolation, except for that of the F protein. These
      results confirm that although hPIV-1 is related to SV, it is antigenically
      distinct from it.

PMID- 1378880
TI  - Localization of group-specific epitopes on the major capsid protein of group A
      rotavirus.
AB  - Chemical cleavage of the VP6 protein of bovine rotavirus showed that VP6-specific
      monoclonal antibodies (MAbs) reacted with the amino acid sequence between glycine
      48 and asparagine 107. Furthermore, three synthetic peptides (amino acids 48 to
      64, 60 to 75 and 91 to 108) containing part of this sequence and 22 consecutive
      overlapping heptapeptides corresponding to the region between amino acids 48 and
      75 were analysed for their immunoreactivity using group-specific MAbs. The MAbs
      recognized peptides 48-64 and/or 60-75, and a set of overlapping heptapeptides
      located between residues 53 (asparagine) and 67 (glycine), which have two short
      sequences in common: IRNW (residues 56 to 59), recognized by MAb RV-133, and
      (NW)NFD (residues 58/60 to 62), recognized by MAbs RV-50, -1026 and -443. These
      results indicate that the sequence between amino acid residues 48 and 75 is
      present in one of the immunodominant sites of VP6.

PMID- 1378881
TI  - Expression of the major core antigen VP7 of African horsesickness virus by a
      recombinant baculovirus and its use as a group-specific diagnostic reagent.
AB  - The major core protein, VP7, of African horsesickness virus serotype 4 (AHSV-4),
      the aetiological agent of a recent outbreak of the disease in southern Europe,
      was expressed in insect cells infected with a recombinant baculovirus containing
      a cloned copy of the relevant AHSV gene (S7). Analyses of its biochemical and
      antigenic properties confirmed the authenticity of the protein expressed. The
      high-level expression of VP7 under the control of the strong polyhedrin promoter
      of Autographa californica nuclear polyhedrosis virus induced disc-shaped crystals
      in infected insect cells. This enabled us to purify the protein by a one-step
      ultracentrifugation procedure and to utilize it for the detection of antibodies
      raised in horses to various serotypes of AHSV. A serological relationship between
      AHSV and two other orbiviruses, bluetongue virus and epizootic haemorrhagic
      disease virus, was also demonstrated.

PMID- 1378882
TI  - Murine monoclonal antibodies directed against the transmembrane protein gp41 of
      human immunodeficiency virus type 1 enhance its infectivity.
AB  - Monoclonal antibodies (MAbs) were raised against the transmembrane protein (TM)
      gp41 of human immunodeficiency virus type 1 (HIV-1, strain HTLV-IIIB). The
      reactivity of three TM-specific MAbs was investigated in several tests, ELISA,
      immunostaining of Western blots, immunofluorescence and an alkaline phosphatase
      anti-alkaline phosphatase assay. Epitope mapping was done by using overlapping
      gp41 peptides produced as Escherichia coli fusion proteins and synthetic
      peptides. In an in vitro assay, all three MAbs showed enhancing effects on HIV-1
      infection after single or repeated treatment with the purified MAbs at
      concentrations of 6 to 25 micrograms/ml. The enhancing domain is located between
      amino acids 724 and 752 of the env protein sequence. Homologous peptides based on
      this sequence were used for analysis of sera from 100 individuals at different
      stages of HIV infection to evaluate the relevance of antibodies against this
      region to the prognosis of disease. No antibodies reactive with this region were
      found in ELISA, indicating that this domain is not immunogenic in humans.

PMID- 1378883
TI  - De novo reverse transcription is a crucial event in cell-to-cell transmission of
      human immunodeficiency virus.
AB  - The proposal that replication of human immunodeficiency virus type 1 (HIV-1),
      mediated by cell-to-cell transmission of the virus, might bypass de novo reverse
      transcription was tested by using one-step cell-to-cell and cell-free virus
      infection systems. Two well characterized reverse transcriptase (RT) inhibitors,
      azidothymidine at 20 microM and phosphonoformic acid at 100 micrograms/ml,
      blocked HIV replication completely following both cell-free virus and cell-to
      cell transmission infection, as determined from the kinetics of unintegrated
      viral DNA synthesis and supernatant RT production after virus infection. Our
      results confirm that de novo reverse transcription is a crucial and mandatory
      event in HIV-1 replication following cell-to-cell transmission of the virus.

PMID- 1378884
TI  - The amino terminus of human cytomegalovirus glycoprotein B contains epitopes that
      vary among strains.
AB  - We mapped three antigenic domains of continuous epitopes on human cytomegalovirus
      (CMV) glycoprotein B (gB) by reacting a panel of independently derived monoclonal
      antibodies with deletion mutants expressed transiently in COS-1 cells. One of
      these antigenic domains, DC2, maps in the last 75 amino acids of the carboxy
      terminus. These epitopes are conserved in strains Towne and AD169, as well as in
      19 clinical CMV isolates. ELISAs of DC2-reactive antibodies with a set of
      overlapping synthetic oligopeptides from the carboxy terminus showed that the
      epitopes of antibodies CH405-1 and CH421-5 map between amino acids 833 and 852
      and that the epitope of antibody CH28-2 maps between amino acids 878 and 898.
      These linear epitopes were grouped into domain DC3. The third antigenic domain,
      DC1v, maps at the amino-terminal end of CMV strain AD169 gB but is not contained
      in strain Towne or in 17 of 19 clinical isolates. Epitopes in this domain are
      likely to map between amino acids 28 and 67, an area where differences occur in
      the nucleotide sequence of the gB genes from AD169 and Towne. Analysis of CMV
      infected cells by flow cytometry with antibodies to the amino- and carboxy
      terminal domains revealed that the amino terminus of gB is extracellular and that
      the carboxy terminus is not exposed on the cell surface.

PMID- 1378885
TI  - Serum prostate-specific antigen: the most useful tumor marker.

PMID- 1378886
TI  - Prostate-specific antigen as a predictor of radiotherapy response and patterns of
      failure in localized prostate cancer.
AB  - PURPOSE: A study of preradiation and postradiation, serial serum prostate
      specific antigen (PSA) levels was performed in patients who had clinically
      localized prostate cancer. The prognostic value of the PSA in pretreatment
      evaluation and posttreatment follow-up was assessed. PATIENTS AND METHODS: Sixty
      three patients who presented with clinically localized prostate cancer and who
      were treated with external-beam radiation therapy were followed-up for a median
      of 25 months. A serum PSA and physical examination were performed at 3-month
      intervals, and a bone scan was done yearly. An increase in PSA triggered an
      additional metastatic workup. Prostate rebiopsy was performed for new, palpable
      nodules or for a serial increase in PSA in the context of a negative metastatic
      workup. RESULTS: Forty-one patients remained recurrence-free and 22 recurred
      clinically, 15 distantly and seven locally. The PSA was the strongest,
      independent, pretreatment prognostic indicator (P = .019) among pretreatment PSA,
      stage, and grade, but lost significance when the serum prostatic acid phosphatase
      (PAP) status was included. The initial rate of the PSA decrease after radiation
      (median half-life, 2.6 months) failed to predict outcome. Recurrence-free
      patients reached postradiation PSA levels that were equivalent to those reported
      in disease-free male populations; failure of the PSA to reach such normal levels
      was a multivariate predictor of subsequent failure (P less than .037). All
      clinicopathologic documentations of failure were preceded by an increase in PSA
      levels during follow-up. Delayed versus early PSA increase was associated with
      clinically localized versus metastatic first recurrence. CONCLUSIONS: The serum
      PSA is an independent pretreatment and posttreatment predictor of outcome.
      Additionally, for a median follow-up of 25 months, delayed PSA failure is
      associated with clinically localized rather than metastatic recurrence, a
      relationship that may help in selection for local salvage therapy.

PMID- 1378887
TI  - Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an
      escalating dose schedule in treatment of metastatic bone cancer.
AB  - Samarium-153 emits medium-energy beta particles and an imageable gamma photon
      with a physical half-life of 46.3 hr. When chelated to
      ethylenediaminetetramethylenephosphonic acid (EDTMP), it is remarkably stable in
      vitro and in vivo. In this study, we administered escalating amounts of 153Sm
      EDTMP, from 0.1 to 1.0 mCi/kg (3.7-37 MBq/kg), to 22 patients with painful
      metastatic bone cancer. A complete concordance was found when the scintigrams of
      153Sm-EDTMP were compared qualitatively to 99mTc-HDP bone images. Moreover, the
      skeletal uptake of the 153Sm-EDTMP related to the number of metastatic sites (r =
      0.65; p = 0.001) showed an inverse proportion to the plasma radioactivity at 30
      min following injection (r = -0.79; p = 0.0001) and was unaffected by the
      administered (mCi/kg), (r = 0.33; p = 0.13). Myelotoxicity was observed in 10 of
      the 29 treatment courses and leukopenia occurred in two. Thrombocytopenia
      occurred in patients who had low pretreatment platelet counts, albeit within the
      normal range (p = 0.001), most suffered from prostate cancer (p = 0.007) and
      retained a higher percentage of the 153Sm-EDTMP in their skeleton (p = 0.057). In
      four patients an exacerbation of the pre-existing pain ("flare reaction") was
      recorded. Pain palliation occurred in 65% of the treated patients (mean: 3.8 mo,
      range: 1-11 mo). Retreatment in first time responder patients was quite
      effective. Our preliminary results indicate that 153Sm-EDTMP is a promising
      radiotherapeutic agent for palliative treatment of metastatic bone cancer pain,
      and further study is necessary to ascertain its optimal dose, efficacy and
      toxicity.

PMID- 1378888
TI  - Early response of canine temporomandibular joint tissues to arthroscopically
      guided neodymium: YAG laser wounds.
AB  - A neodymium yttrium aluminum garnet (Nd:YAG) laser inserted through an operating
      arthroscope was used to introduce applied energy to synovial tissues, articular
      discs, and bone in the temporomandibular joint of mongrel dogs. Arthroscopic
      inspection of the wounds was performed at 1 and 2 weeks postoperatively. The
      animals were killed and the temporomandibular joints were examined grossly and
      histologically to determine the extent of injury and healing. The results show
      that laser wounds of bone and articular disc undergo no repair, whereas laser
      wounds of synovium show rapid repair. Laser damage to condylar marrow under an
      articular disc wound was unexpectedly found.

PMID- 1378889
TI  - Clear-cell variant of mucoepidermoid carcinoma: report of a case with
      immunohistochemical and ultrastructural observations.

PMID- 1378890
TI  - A neuroendocrine cause of oncogenic osteomalacia.
AB  - All definite cases of oncogenic osteomalacia have, until now, been classified as
      mesenchymal tumours. We report here a case of oncogenic osteomalacia caused by a
      spinal tumour. Microscopically, it resembled the mixed connective tissue variant
      of previously described phosphaturic tumours. Immunohistochemical studies,
      however, showed the tumour cells to be positive for low molecular weight
      cytokeratin (CAM 5.2), S100 protein, PGP 9.5, and synaptophysin. Electron
      microscopy demonstrated neurosecretory granules. The histopathological findings
      strongly suggest that this is a neuroendocrine tumour.

PMID- 1378891
TI  - A study of adhesion molecules as markers of progression in malignant melanoma.
AB  - Adhesion molecules are substances which are involved in the interactions between
      cells, and between cells and the extracellular matrix in both benign and
      malignant tissues. Two members of this group--intercellular adhesion molecule-1
      (ICAM-1) and MUC18--have previously been found to be expressed on melanoma;
      however, studies seeking a correlation between expression and metastatic
      behaviour have yielded conflicting results. In this study we investigated the
      expression of these two antigens and that of a number of other adhesion molecules
      [VCAM-1, ELAM, and the neural cell adhesion molecule (NCAM)] on a range of benign
      and malignant melanocytic lesions. Both ICAM-1 and MUC18 were found on a high
      percentage of all melanocytic lesions including benign naevi. VCAM-1 was found to
      be expressed on 79 per cent of benign naevi, 62 per cent of primary melanomas
      less than 1.5 mm in depth, and 6 per cent of thick primaries. The antigen was
      present on 14 per cent of lymph node metastases and on no extranodal deposits.
      This suggests that loss of melanoma cell adhesion mediated by VCAM-1 may be
      important in the development of metastatic melanoma.

PMID- 1378892
TI  - Interstitial pneumonia in simian immunodeficiency virus infection.
AB  - Interstitial pneumonia unrelated to Pneumocystis carinii or other infections was
      observed histopathologically in 5 of 25 rhesus monkeys infected with simian
      immunodeficiency virus (SIV). The predominant lesion was lymphocytic infiltration
      of interalveolar septa and hyperplasia of peribronchial and perivascular lymphoid
      tissue. Immunohistochemical staining using a panel of antibodies against human T
      and B lymphocytes, macrophages, and immunoglobulins showed that peribronchial
      aggregates and interstitial infiltrates were predominantly B cells, whereas
      perivascular masses consisted mainly of T cells. One animal with a primary B-cell
      lymphoma of the spinal cord had secondary plasmacytoid lymphomatous nodules
      throughout the lung which were accompanied locally by reactive B-cell lymphoid
      follicles. Another animal also had large areas of diffuse alveolar fibrosis and
      epithelial metaplasia to a bronchiolar type. In two monkeys, branches of the
      pulmonary arteries showed intimal proliferation and organizing occlusive thrombi,
      some of which were mineralized.

PMID- 1378893
TI  - The Bologna Eubiosia Project: hospital-at-home care for advanced cancer patients.
AB  - Since 1985 the Associazione Nazionale per lo Studio e la Cura dei Tumori Solidi
      (ANT), an Italian nonprofit anticancer organization, has provided a hospital-at
      home care program for advanced and very advanced cancer patients. This program is
      part of the Eubiosia Project which also includes a number of complementary
      services. Teams of doctors, nurses, and psychologists work round-the-clock in the
      region and on hospital wards, assisted by diagnostic and therapeutic facilities
      applicable at home and by a round-the-clock on-call service seven days a week.
      The patients who were treated between December 1985 and December 1991 numbered
      5603, of whom 2130 received treatment in 1991 alone, with 702 patients on line at
      the end of the period. The mean duration of home care for the first 2803 deceased
      patients was 62 days, and the percentage of deaths at home was 70%. We analyzed
      control of the main symptoms and the residual survival in three groups of
      patients--stomach, lung, and breast cancer sufferers--and found that acceptable
      pain control was achieved in 95% of cases. From the retrospective analysis of our
      data it can be seen that the eligibility criteria for entry to home care should
      not only depend upon performance status and the presence of symptoms, but should
      also take into account the factors that are inherent to the natural history of
      any kind of tumor as well as the social, domestic, and psychological
      characteristics of the patients.

PMID- 1378894
TI  - Palliative care--could your patient have been managed at home?
AB  - Palliative care, supportive care of the dying, is rapidly changing to better meet
      the needs of the patients and families. If palliative care is provided in the
      home rather than in hospital, there is a potential for improvement in the quality
      of life for patients and their families and a potential for cost reduction in the
      health care system. Our study was undertaken to determine whether or not
      palliative care patients admitted to University Hospital could have been cared
      for at home rather than in the hospital. The hospital charts of 96 palliative
      care patients were reviewed retrospectively. The results indicated that 61% of
      these palliative care patients did not receive any palliative care at home and
      that 94% died in an acute care hospital setting. Only 18% lived in a setting
      other than their own home, and 68% had a spouse or other family member living
      with them at the time of their final admission. Based on the level of support in
      the place of residence prior to final admission and the reasons for admission, we
      determined that many of the patients could have been managed at home for at least
      some of the palliative care period if appropriate support from a home care team
      had been available.

PMID- 1378895
TI  - Palliative care needs of residents, families, and staff in long-term care
      facilities.
AB  - While there is growing recognition that the physical needs of LTC residents have
      increased markedly in the 20 years, the palliative care needs of facility
      residents and their families are poorly understood. There also is a dearth of
      information on the educational and support needs of LTC facility staff vis-a-vis
      palliative care. Operating from the Juan de Fuca Hospital Society (a network of
      extended care facilities in Victoria), our Palliative Support Team (PST) was
      conceived in order to act as an educational resource to JdF staff as well as to
      provide expert consultation on palliative care issues. As part of the evaluation
      of this pilot program, a sample of 74 Juan de Fuca workers were interviewed to
      determine their perceptions of resident, family, and staff needs in relation to
      palliative care. In this paper, discussion is focused on the palliative care
      needs identified by professional caregivers. The ways in which a palliative care
      consultation team can address some of these needs are also discussed.

PMID- 1378896
TI  - Clinical ethics and palliative care in clinical practice.

PMID- 1378897
TI  - The role of a mobile palliative care team in the field of clinical ethics.

PMID- 1378898
TI  - The program of palliative medicine and care in the curriculum of sixth-year
      medical students in Poland.

PMID- 1378899
TI  - Palliative care in Colombia: problems and satisfactions.

PMID- 1378900
TI  - New perspectives in the treatment of decubitus ulcers.
AB  - Although the consequences of prolonged lying on a hard surface are as old as the
      human race, publications on this subject are scarce. This is due to the fact that
      a decubitus ulcer never occurs in isolation but is nearly always a complication
      of some other condition. The term "decubitus" was already used by Hildnaus in
      1590 and is derived from the Latin word decumbere which means "lying down". The
      most important fact to keep in mind is that pressure sores can be prevented. This
      is the reason why this article not only discusses the management of pressure
      sores but also the importance of preventive measures. The basis of effective
      treatment is early detection and an adequate knowledge of the fundamental
      pathological process. Only adequate preventive measures, careful examination of
      the lesions, and a thorough knowledge of the products used can avoid unnecessary
      suffering by patients.

PMID- 1378901
TI  - The discovery of (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-
      azabicyclo[2.2.2]-octan-3-amine as a novel, nonpeptide substance P antagonisst.
AB  - We describe the structure-activity relationship development of a series of
      quinuclidines which culminated in the first potent, selective, nonpeptide
      substance P (SP) antagonist, (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxy
      phenyl)methyl]-1- azabicyclo[2.2.2]octan-3-amine, 3 (CP-96,345). Compound 3 is a
      potent displacer of [3H]SP binding in human IM-9 cells and blocks SP-induced and
      capsaicin-induced plasma extravasation, as well as SP-induced salivation in the
      rat in vivo. This compound may both help to further our understanding of the
      interactions of small molecules with peptide receptors and serve to evaluate the
      therapeutic potential of a SP antagonist.

PMID- 1378903
TI  - Doctors lack training in hospice care.

PMID- 1378902
TI  - A hyperpolarization-activated inward current in human myocardial cells.
AB  - Normally-polarized tissue from the human atrial myocardium usually exhibits a
      diastolic depolarization phase which can be suppressed reversibly by Cs+ or
      enhanced by inhibiting the inward rectifier K+ current, iK1, with Ba2+. (Escande
      et al., 1986). Because the suppression of the diastolic slope by Cs+ leads to a
      hyperpolarization of the cell membrane at the end of the diastolic phase, it was
      suggested that Cs+ might inhibit an inward current responsible for diastolic
      depolarization. Among the ionic mechanisms underlying the diastolic
      depolarization phase of cardiac tissues, the hyperpolarization-activated inward
      current, if, fits well to explain the small diastolic slope of human atrial
      fibres. In other preparations, this inward current carried both by Na+ and K+
      ions is rapidly deactivated during the action potential and entirely blocked by
      millimolar concentrations of Cs+ (DiFrancesco 1981; DiFrancesco, et al., 1986;
      Kokubun et al., 1982; Callewaert et al., 1984; Denyer and Brown, 1990). Such a
      current in human myocardial cells has not been characterized so far although its
      existence in human atrial trabeculae was previously reported in an abstract
      (Carmeliet, 1984). In the present study, we describe an inward current which
      activates upon hyperpolarization in patch-clamped single human atrial cells and
      shares similar characteristics with the if pacemaker current described in
      unicellular and intact preparations of mammalian cardiac tissues.

PMID- 1378904
TI  - Antiproliferative potencies of interferons on melanoma cell lines and xenografts:
      higher efficacy of interferon beta.
AB  - BACKGROUND: Human melanomas have shown only limited responsiveness to clinical
      therapy with interferon (IFN). PURPOSE: Our aim was to determine the most
      effective class of IFN for inhibiting growth of melanoma cells and to establish
      whether variation exists in response of various cell lines to different IFNs.
      METHODS: We compared the direct antiproliferative effects of the type I IFN alpha
      2b, IFN alpha-4a, and IFN-beta and the type II IFN-gamma on eight melanoma cell
      lines grown in vitro. We did this comparison by determining the concentration of
      each IFN that resulted in 50% growth inhibition, using the MTT [3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium tetrazolium bromide] dye uptake method. We
      also tested IFN alpha-2a and IFN-beta for their ability to inhibit the growth of
      xenografts of the LiBr melanoma cell line in vivo in nude mice. Receptor binding
      was determined using [35S]methionine-labeled IFN alpha-4a, in competition with
      unlabeled IFN alpha-2b, IFN alpha-4a, and IFN-beta. RESULTS: The melanoma cell
      lines differed markedly in their sensitivity to the IFNs tested: Five were
      sensitive to low concentrations (less than 30 pM) of IFN-beta, only one was
      sensitive to similar concentrations of IFN alpha-2b, and none were sensitive to
      IFN alpha-4a at concentrations up to 920 pM. For all cell lines, the
      antiproliferative potency of the type I IFNs was IFN-beta greater than IFN alpha
      2b greater than IFN alpha-4a. IFN-gamma was less active than IFN-beta on all
      except one of the cell lines. Similarly, IFN-beta was more potent than IFN alpha
      2a in inhibiting the growth of the LiBr xenograft in nude mice. Labeled IFN alpha
      4a bound with high specificity in all four melanoma lines tested, and competitive
      binding experiments showed that the order of binding affinity (IFN-beta greater
      than IFN alpha-2b greater than IFN alpha-4a) correlated with the order of
      antiproliferative potency. CONCLUSION: The finding that melanoma cell lines
      differ intrinsically in their sensitivity to IFNs may explain differences in
      clinical response. Our results suggest that IFN-beta may be the most effective
      IFN in the treatment of melanoma, although confirmation will require clinical
      trials involving large numbers of patients.

PMID- 1378905
TI  - Severe myelosuppression resulting from concurrent administration of granulocyte
      colony-stimulating factor and cytotoxic chemotherapy.

PMID- 1378906
TI  - Transrectal microwave hyperthermia for benign prostatic hyperplasia: long-term
      clinical, pathological and ultrastructural patterns.
AB  - Transrectal microwave hyperthermia of the prostate was administered to 191
      patients with bladder outlet obstruction due to benign prostatic hyperplasia who
      were either at poor operative risk or who refused surgery. Patients were divided
      in 2 groups according to age and they underwent either 5 or 10, 60-minute
      sessions of hyperthermia, with a calculated intraprostatic temperature of 42.5
      plus or minus 0.5C. Light and electron microscopy showed no irreversible damage
      at the glandular epithelium but did demonstrate a significant increase in
      neoformed intraprostatic capillary-like vessels. At 1, 12 and 24 months residual
      urine volume was significantly decreased in the majority of patients but only a
      minor amelioration of urinary flow rates and subjective symptoms was observed.
      According to maximum flow nomograms all patients were still obstructed
      postoperatively. Transrectal hyperthermia cannot be considered a genuine
      alternative to surgery for patients with bladder outlet obstruction due to benign
      prostatic hyperplasia.

PMID- 1378907
TI  - Effect of Casodex on sleep-related erections in patients with advanced prostate
      cancer.
AB  - Sleep-related erections in 5 patients with stage T3N0M0 prostate cancer treated
      with a new nonsteroidal antiandrogen, Casodex, were evaluated with continuous
      monitoring of penile tumescence and rigidity on multiple nights. Mean serum
      luteinizing hormone levels were 7.2 +/- 1.2 IU/l. before therapy and increased to
      14 +/- 3.6 IU/l. after 6 months of therapy. Serum testosterone and estradiol
      levels also increased from a basal level of 5.05 +/- 1.9 ng./ml. and 102 +/- 18
      pmol./l., respectively, to 8.04 +/- 1.32 ng./ml. and 175 +/- 20 pmol./l.,
      respectively, after 6 months of therapy. No significant modifications in regard
      to number of nocturnal penile tumescence episodes, maximum penile circumference
      and total rigidity time were found before and after therapy. Only 1 patient
      reported a decrease in sexual drive and libido. All patients presented with
      stable disease (National Prostatic Cancer Treatment Group criteria) and an
      unmodified performance status (Eastern Cooperative Oncology Group) after 6
      months. Pure antiandrogen therapy did not seem to interfere significantly with
      the erectile capability of men with prostate cancer.

PMID- 1378908
TI  - Transrectal microwave hyperthermia for advanced prostate cancer: long-term
      clinical results.
AB  - Transrectal microwave hyperthermia was applied to 46 stages D1 and D2 prostate
      cancer patients to treat urinary symptoms and local pain unrelieved by total
      androgen ablation therapy. Hyperthermia was administered in 10, 60-minute
      sessions twice a week for 5 weeks. A calculated intraprostatic temperature of
      43.5 +/- 0.5C was maintained throughout the treatment. At 2 years the mean
      residual urine volume was significantly decreased (p less than 0.05), while the
      mean peak flow rate and maximum flow nomogram were improved but not
      significantly. The majority of patients reported a notable amelioration of
      subjective symptoms and quality of life. The only complication was a
      prostatorectal fistula that was cured by leaving a urethral catheter in place for
      4 weeks. Prostatic hyperthermia is a safe and effective palliative procedure for
      bladder outlet obstruction due to advanced prostate cancer.

PMID- 1378909
TI  - Quantitative morphometry of the adult human bladder.
AB  - The primary objective of the present retrospective study was to characterize the
      effects of aging and BPH on bladder morphometry. Eighty-six bladder specimens
      were obtained from the autopsy archives of the Milwaukee County Medical Complex.
      The bladder specimens were divided into 4 groups based upon age and gender: Group
      I: males between the ages of 35-45 years; Group II: males between the ages of 65
      75 years; Group III: females between the ages of 35-45 years; and Group IV:
      females between the ages of 65-75 years. The age groups were selected in order to
      identify a group of males with and without BPH. The area density of smooth
      muscle:connective tissue was determined in bladder specimens using color assisted
      computer image analysis. Masson-trichrome and double immunoenzymatic staining
      techniques were used to discriminate the smooth muscle and connective tissue
      elements of the bladder. The area density of smooth muscle:connective tissue in
      the Masson-trichrome stained sections was significantly greater in Group I vs.
      Group II (2.90 +/- 0.22 vs. 2.33 +/- 0.16) and in Group III vs. Group IV (2.85 +/
      0.13 vs. 2.03 +/- 0.20). Aging was associated with a decrease in the area
      density of smooth muscle:connective tissue ratio in both males and females. The
      area density of smooth muscle:connective tissue was not significantly different
      in younger males and females (Group I vs. Group III) and older males and females
      (Group II vs. Group IV). The present morphometric study suggests that aging and
      not BPH, is associated with a relative increase in detrusor fibrosis.
      Infravesical obstruction in BPH may effect bladder function via mechanisms
      unrelated to the histologic composition of the bladder.

PMID- 1378910
TI  - Urinary tissue factor levels in transitional cell carcinoma of the bladder.
AB  - Production of procoagulant activity by host and tumour cells may be increased in
      patients with cancer. Using a simple chromogenic assay, we have determined
      urinary tissue factor (TF) levels in patients presenting with transitional cell
      carcinoma of the bladder (TCC, n = 63), normal controls (n = 20) and patients
      with benign prostatic hypertrophy (BPH, n = 35). In addition, a separate cohort
      of patients undergoing endoscopic surveillance for superficial bladder cancer
      were studied to determine whether there was any difference in levels in those
      with recurrent disease compared to those with normal cystoscopies. Urinary TF
      activity was higher in TCC compared to controls (p less than 0.001) and patients
      with BPH (p less than 0.05). In patients undergoing check cystoscopy, those with
      recurrent disease (n = 32) had higher levels (p less than 0.01) than those with
      normal examinations (n = 21). It is concluded that urinary TF levels are elevated
      in bladder cancer and that this reflects disease activity in those at risk of
      recurrent superficial disease.

PMID- 1378911
TI  - [Clinical evaluation of effects of KRN8601 (rhG-CSF) on neutropenia].
AB  - Clinical effects of KRN8601 (recombinant human granulocyte colony-stimulating
      factor:rhG-CSF) were studied in 26 patients with chronic neutropenia including 4
      Kostmann's disease, 1 Shwachman's syndrome, 1 Lonsdale's syndrome, 1 glycogen
      storage disease Ib-associated, 6 chronic benign, 5 chronic hypoplastic, 2 cyclic,
      4 autoimmune and 2 miscellaneous neutropenia. The patients were given rhG-CSF
      intravenously at doses of 20-540 micrograms/m2 or subcutaneously at doses 20-400
      micrograms/m2, over the periods of 2-32 weeks. Increases in neutrophil counts
      occurred after rhG-CSF administration in 23 of the 26 patients. Patients with
      Kostmann's disease, Shwachman's syndrome and chronic hypoplastic neutropenia
      responded poorly compared to patients with other types of neutropenia. There were
      no serious side effects which caused interruption of the study. These results
      indicated a beneficial effect of KRN8601 in various types of chronic neutropenia.

PMID- 1378912
TI  - [Immunocytochemical staining of decay-accelerating factor (DAF) on erythrocytes:
      paroxysmal nocturnal hemoglobinuria (PNH)].
AB  - Affected erythrocytes in patients with paroxysmal nocturnal hemoglobinuria (PNH)
      have been detected as complement-sensitive cells by the complement sensitivity
      assay. Decay-accelerating factor (DAF), a molecular mass of 70 kDa complement
      regulatory membrane glycoprotein, has been reported to be deficient on affected
      PNH blood cells. In the present study, DAF on erythrocytes from 12 patients with
      PNH were stained by an immunocytochemical method and the ratio of DAF+
      erythrocytes was compared with their laboratory data concerning hemolysis, almost
      all normal human erythrocytes stained positively for DAF. In contrast, various
      percentages of DAF+ erythrocytes were found in the patients with PNH. The
      percentages of DAF+ erythrocytes correlated positively with the total amounts of
      DAF on erythrocytes measured by an enzyme-linked immunosorbent assay (ELISA),
      negatively with % hemolysis in Ham's test and in sucrose hemolysis assay and with
      percentages of PNH type III (PNH-III) erythrocytes. In some patients with PNH,
      subpopulations of erythrocytes weakly-positive for DAF were demonstrated in
      addition to DAF- erythrocytes. The immunocytochemical method for staining DAF on
      erythrocytes developed in the present study is useful for the detection of
      affected PNH erythrocytes and applicable to further studies on membrane defects
      in PNH.

PMID- 1378913
TI  - Alterations of anionic charge and/or sites of the glomerular basement membrane in
      the heterologous phase of passive Heymann nephritis.
AB  - Alterations of the anionic charge and/or sites of the glomerular basement
      membrane (GBM) in the heterologous phase of passive Heymann nephritis (PHN) were
      studied. Rats with PHN induced by a single injection of anti-Fx1A IgG were
      examined at days 1, 2, 3 and 4. The left kidney was perfused with ruthenium red
      (RR) solution as a cationic probe. The RR particles (= anionic sites) in the GBM
      were counted and expressed as the number of RR particles per unit length of GBM.
      For quantitative determination of the total anionic charge of the GBM, the GBM
      bound ruthenium (= anionic charge) was measured with an atomic absorption
      spectrophotometer (AAS). Abnormal proteinuria corresponding to a decrease in
      anionic charge was detected at days 3 and 4. The anionic sites in the lamina rara
      externa (LRE) adjacent to immune complex (IC) deposits were found to have
      diminished earlier from day 1 onwards. This diminution was largely confined to
      areas adjacent to the IC deposits and was significantly correlated with the
      amount of urinary albumin excretion. Proteinuria in the heterologous phase of PHN
      would thus appear to be causally related to a decrease in the number of anionic
      sites in the LRE adjacent to IC deposits.

PMID- 1378914
TI  - The REM rhythm of depression in daytime and sleep EEG.

PMID- 1378915
TI  - Enzyme studies of methotrexate-resistant human leukemic cell (K562) subclones.
AB  - Five methotrexate (MTX)-resistant K562 cell subclones (K562/MTX-1 approximately 
      5) were established and were examined for mechanisms of drug resistance.
      Impairment of MTX-polyglutamate formation, with membrane transport alteration, in
      the resistant cells was demonstrated in the previous studies (Koizumi, S. (1988)
      Jpn. J. Cancer Res. 79, 1230). Further analysis of sensitivity of the cells to
      trimetrexate (TMQ), which is not polyglutamated and does not require the reduced
      folate transporter, but is a potent inhibitor of human DHFR, revealed a modest
      decrease in sensitivity to TMQ (2.4- to 15-fold). Enzyme studies showed that the
      dihydrofolate reductase (DHFR) activities of these resistant subclones were very
      similar to that of the parent cells. The number of binding sites of these
      subclones for MTX calculated from Scatchard analysis was increased up to 7-fold
      in the K562/MTX-1 and -4 subclones and up to 3-fold in the other 3 subclones as
      compared to the parent cells. KD values of MTX for the DHFR in the K562/MTX-1 and
      -4 subclones also appeared to be altered relative to the parent cell line.
      Further, thymidylate synthase (TS) activity of the resistant subclones was
      reduced to 50% in K562/MTX-1 and -4 cells, and to 11-25% in the other subclones
      as compared to the parent cell line. These findings suggest that antifolate
      resistance in the newly established K562/MTX subclones in multifactorial with
      polyglutamation and transport defects accounting for the majority of resistance
      to MTX, and that alteration in the binding affinity of DHFR for MTX and
      diminished levels of TS may contribute to the 'residual' drug resistance to TMQ
      and have importance with respect to MTX.

PMID- 1378916
TI  - Synergistic induction of the differentiation of WEHI-3B D+ myelomonocytic
      leukemia cells by retinoic acid and granulocyte colony-stimulating factor.
AB  - Retinoic acid (RA) has been shown to be an inducer of the terminal
      differentiation of several leukemia cell lines in vitro and in clinical trials to
      produce a high percentage of remissions in patients with acute promyelocytic
      leukemia. In an effort to increase the therapeutic efficacy of RA, we have
      measured the capacity of granulocyte colony-stimulating factor (G-CSF) to enhance
      the differentiation inducing activity of RA in WEHI-3B D+ monomyelocytic leukemia
      cells. Combinations of G-CSF and RA produced a supra-additive increase in the
      percentage of WEHI-3B D+ cells reducing nitro blue tetrazolium and expressing Mac
      1 (CD11b) antigen on the cell surface, two markers of the mature state. In the
      presence of 50 ng/ml of G-CSF, which produced only 12% differentiation when used
      alone, 0.5 microM RA induced the same degree of cellular differentiation as the
      optimum concentration of RA (i.e. 7 microM) employed alone. The supra-additive
      differentiation produced by this combination was prevented by the presence of G
      CSF monoclonal antibody in the culture medium, resulting in a degree of
      maturation comparable to that produced by the retinoid alone. When cells were
      sequentially exposed to G-CSF followed by RA, a much higher level of
      differentiation was obtained than when the order was reversed, suggesting that
      WEHI-3B D+ cells were primed to enter a differentiation pathway by G-CSF. The
      supra-additive terminal differentiation exhibited by the mixture of G-CSF and RA
      suggests that these agents should be evaluated for the therapeutic efficacy of
      the combination in patients with acute non-lymphocytic leukemia.

PMID- 1378917
TI  - Characterization of two novel pre-B-cell lines (LK63 and LiLa-1): potential
      models of pre-B-cell differentiation.
AB  - In this report we describe two newly isolated pre-B acute lymphoblastic leukaemia
      cell lines. Both cell lines lack EBV as detected by the EBNA-1 gene probed
      Southern-blots. Neither cell line expressed the B-cell-specific CD20 antigen on
      the cell membrane. However surface expression of CD20 was induced by phorbol
      ester (TPA) on both LiLa-1 and LK63 cell lines. Other pre-B and B-cell lines,
      such as Reh, Nalm-1, and BALL-1 did not exhibit these changes in phenotype.
      Previous immunoprecipitation studies have noted that a broad 50-55 kD band co
      precipitates with the characteristic 33-37 kD CD20 protein. We demonstrate that,
      while the 33-37 kD CD20 species was undetectable on resting LiLa-1 and LK63
      cells, in each case a 50-55 kD protein was immunoprecipitated by the CD20
      antibody. However, the failure to detect any cell surface CD20-associated antigen
      on the control cells by immunophenotyping indicated that the CD20 epitope of the
      50-55 kD molecule was not expressed on the cell surface. Following exposure to
      TPA the 50-55 kD species was reduced over 48-72 h while the level of the p33-37
      CD20 protein was increased. Northern-blot analysis showed that the 50-55 kD
      protein was not a cryptic form of CD20 as the uninduced cells contained no
      detectable CD20 mRNA. The decrease of the 50-55 kD protein and the acquisition of
      the mature CD20 molecule were paralleled by a decline in proliferative activity
      in both cell lines. As expression of CD20 by normal pre-B cells also coincides
      with the cessation of cell division and maturation towards a mature B-cell
      phenotype, these cell lines appear to represent models for a discrete stage of B
      cell differentiation which may be valuable in defining the signals regulating pre
      B-cell proliferation.

PMID- 1378918
TI  - Myeloblastoma formation in acute myeloid leukemia.
AB  - The cell surface markers on the leukemic cells of 76 patients with adult acute
      myeloid leukemia (AML) have been analyzed by indirect immunofluorescence, and the
      presence of CD56+ leukemic cells was detected in ten of these patients. Four of
      these 10 CD56+ AML patients developed extramedullary myeloblastomas and in two of
      them an intracranial myeloblastoma. In contrast, in the remaining 66 CD56- AML
      patients, only one patient developed a myeloblastoma formation of the
      subcutaneous. It may be that the CD56 antigen which is an isoform of the neural
      cell adhesion molecule (NCAM), expressed on neurons, satellite cells of skeletal
      muscle cells, and on stromal cells, binds these tissues by a homophilic
      mechanism. CD56+ leukemic cells are capable of invading and of surviving in
      extramedullary tissues, where they proliferate and develop into a myeloblastoma.
      Because of this possibility, CD56+ AML patients should be carefully monitored for
      signs of myeloblastoma formation.

PMID- 1378920
TI  - Computer database for palliative care.

PMID- 1378919
TI  - Susceptibility of acute myelogenous leukemia blasts to lysis by lymphokine
      activated killer (LAK) cells and its clinical relevance.
AB  - To help understanding host-tumor relationships in acute myelogenous leukemia
      (AML) and better define indications for interleukin 2 (IL-2) therapy in this
      disease, we studied the relationship between the susceptibility of leukemic cells
      of 44 AML patients to lysis by autologous (26 cases) and/or allogeneic (41 cases)
      lymphokine-activated killer (LAK) cells and characteristics of the leukemia.
      Lymphocytes were activated in the presence of 1000 u/ml recombinant IL-2 for 5
      days. Lysis of AML cells was studied by 51Cr release. Average lysis of AML cells
      by autologous LAK cells was 9 +/- 13% and by allogeneic LAK cells 10 +/- 9% with
      a significant correlation between lyses by both effectors (p = 0.01). Autologous
      (p = 0.005) and allogeneic (p = 0.004) lyses were higher in patients with initial
      infection. Allogeneic lysis was correlated with initial WBC count (p = 0.009),
      serum lactic-dehydrogenase level (p = 0.05), and expression of CD13 (p = 0.01).
      Autologous lysis was inversely correlated with expression of CD34 (p = 0.003).
      Expression of adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3) by the leukemic
      cells did not correlate with their lysis by LAK cells. Susceptibility of leukemic
      cells to lysis by LAK cells did not correlate with prognosis of the leukemia.

PMID- 1378921
TI  - Characterization by enriched polyclonal antibodies of developmentally regulated
      and cell type specific mouse testis antigens.
AB  - Polyclonal antisera directed against testicular proteins were characterized by
      immunocytochemistry and Western blot analysis. Antibodies binding to testis
      specific, developmentally regulated protein bands were eluted from their antigens
      and used for further characterization of the developmental profile and cell type
      specific expression of two antigens, PSM33 and NNA75. While PSM33 was found to be
      present in spermatocytes from the late pachytene stage on, NNA75 could be
      localized in neonatal interstitial cells. NNA75 expression ceases by to postnatal
      day ten, when first meiosis starts within the seminiferous tubules, thus
      suggesting an interactive role of Leydig cells during the onset of meiotic
      divisions.

PMID- 1378922
TI  - Mutagenesis of Escherichia coli: a method for determining mutagenic specificity
      by analysis of tRNA suppressors.
AB  - A method for estimating mutagenic specificity in Escherichia coli (argE3, hisG4,
      thr-1, supE44), based upon the isolation of Arg+ or His+ revertants and
      identification of tRNA suppressors, is described. The method gives an insight not
      only into mutagenic pathways but also into the functioning of tRNA. With N-methyl
      N'-nitro-N-nitrosoguanidine, 98% of mutations are GC----AT transitions. With N4
      hydroxycytidine, 100% are AT----GC transitions. With hydroxylamine, apart from GC
      ---AT transitions, approximately 30% of Arg+ revertants are formed by GC (or AT)-
      --TA transversions. When the chemistry of the mutagenic attack is known, the
      method allows us to discriminate whether mutations occur on the transcribed or
      non-transcribed strands of DNA. It has been found that reversion of argE3 to Arg+
      is a better monitor of mutagenic pathways than reversion of hisG4 to His+.

PMID- 1378923
TI  - Spermine and related polyamines produce a voltage-dependent reduction of N-methyl
      D-aspartate receptor single-channel conductance.
AB  - Several polyamines have been shown to interact with a site on the N-methyl-D
      aspartate (NMDA) receptor that regulates the binding of open channel blockers.
      Spermine (SP) and spermidine (SD), polyamine agonists, enhanced binding of open
      channel blockers, whereas arcaine (ARC), diethylenetriamine (DET), and putrescine
      (PUT), polyamine antagonists, reduced the polyamine enhancement of open channel
      blocker binding. We previously showed that SP had multiple actions on NMDA
      receptor single-channel currents that underlie its effect on whole-cell NMDA
      receptor current. At high concentrations, SP produced a voltage-dependent
      decrease in NMDA receptor single-channel conductance and average open time. In
      the present study, another polyamine agonist (SD) produced a similar reduction of
      NMDA receptor single-channel conductance at higher concentrations. The polyamine
      antagonists (ARC, DET, and PUT), however, produced a voltage-dependent reduction
      in NMDA receptor whole-cell currents and reductions in single-channel conductance
      and average open time, even in the absence of polyamine agonists. The rank order
      of potency for reduction of NMDA receptor single-channel conductance by
      polyamines was ARC greater than SP greater than SD greater than PUT = DET, a rank
      order similar to that for the inhibitory actions of polyamines in receptor
      binding assays and for the effects of the antagonists on NMDA receptor whole-cell
      currents. The polyamine antagonist DET did not block the reduction of single
      channel conductance by the polyamine agonist SP. In fact, the effects of SP and
      DET on single-channel conductance were additive. DET also showed a variable
      enhancement of NMDA receptor whole-cell currents in some neurons, suggesting
      polyamine agonist-like properties. These results are not consistent with the
      standard pharmacological profile for agonists and antagonists acting at the same
      site. Potential mechanisms for the effects of the polyamines on single-channel
      conductance are discussed.

PMID- 1378924
TI  - Characterization of bicuculline/baclofen-insensitive gamma-aminobutyric acid
      receptors expressed in Xenopus oocytes. I. Effects of Cl- channel inhibitors.
AB  - Poly(A)+ RNA from bovine retina expressed gamma-aminobutyric acid (GABA)
      activated membrane current responses in Xenopus oocytes, consisting of two
      pharmacologically distinct components. One component (IG-Aret) was mediated by
      GABAA receptors, and the other component (KG-BR) by atypical GABA receptors that
      were resistant to inhibition by bicuculline and insensitive to activation by
      baclofen. To further characterize the bicuculline/baclofen-insensitive GABA
      receptors, electrical recordings were made measuring the sensitivity of IG-BR to
      two Cl- channel inhibitors, t-butylbicyclophosphorothionate (TBPS) and
      picrotoxin. For purposes of comparison, effects of TBPS and picrotoxin were also
      assayed on currents mediated by GABAA receptors expressed in oocytes by rat
      cerebral cortex RNA (IG-Actx). The main finding of this study was that TBPS was a
      surprisingly weak inhibitor of IG-BR, whereas IG-Actx was potently suppressed.
      Assays on maximum responses indicated that IG-Actx was at least 500 times more
      sensitive to TBPS than was IG-BR (IC50 values of approximately 0.2 microM and
      greater than 50 microM, respectively). Moreover, inhibition of IG-Actx by
      micromolar concentrations of TBPS was largely insurmountable, whereas the weak
      inhibitory effects on IG-BR showed strong dependence on agonist concentration.
      For example, 10 microM TBPS reduced maximum IG-Actx by greater than 90%, an
      effect that was not significantly reversed by 10-fold increases in the
      concentration of agonist. In contrast, the same concentration of TBPS caused a 2
      fold increase in the EC50 for IG-BR but had only marginal (less than 5%)
      inhibitory effects on maximum responses. Picrotoxin inhibited both types of
      current, but assays on maximum responses indicated that IG-Actx was approximately
      30 times more sensitive than IG-BR (IC50 values of approximately 1 and 30 microM,
      respectively). Inhibitory effects of picrotoxin on IG-BR again showed strong
      dependence on agonist concentration, but in this case there was also a clear
      insurmountable component. Comparisons between IG-Actx and IG-Aret suggested that
      GABAA receptors expressed by either brain or retina RNA showed approximately the
      same sensitivity to TBPS and picrotoxin. Our experiments indicate that the
      bicuculline/baclofen-insensitive GABA receptors expressed by retina RNA differ
      markedly from GABAA receptors in their sensitivity to TBPS and picrotoxin.
      Defining the structural features responsible for these differences at the
      molecular level will provide a further means of investigating the complex
      mechanisms underlying interactions between inhibitors and GABA-activated Cl-
      channels.

PMID- 1378925
TI  - Neutralization of bleomycin hydrolase by an epitope-specific antibody.
AB  - Bleomycin hydrolase (BH) is a cysteine proteinase that terminates the
      pharmacological action of bleomycin (BLM). Amino acid sequence data obtained from
      a tryptic digest fragment of purified rabbit lung BH were used to synthesize a 14
      amino acid peptide (LAVLEQEPIVLPAK; BHP14), which was conjugated to horseshoe
      crab hemocyanin and used to produce rabbit antiserum that was immunoreactive to
      both BHP14 and rabbit BH. Anti-BHP14 binding to BHP14 could be competitively
      blocked by the presence of either BHP14 or BH. Anti-BHP14 recognized both
      purified rabbit liver BH and postmicrosomal fraction from rabbit liver on Western
      blot, as a single band of M(r) approximately 48,000. Anti-BHP14 inhibited, in a
      concentration-dependent manner, BH activity in rabbit liver cytosolic fractions,
      as measured by deamido-BLM A2 formation. Thus, we have generated an epitope
      specific neutralizing antibody to rabbit BH, which can block the metabolism of
      BLM by homogenates from rabbit tissue. These results suggest that the
      LAVLEQEPIVLPA epitope of rabbit BH is involved in the metabolism of BLM or is
      topologically near the active site. Furthermore, a BLM-resistant squamous
      carcinoma (C-10E) exhibited slightly more immunoreactivity, by enzyme-linked
      immunosorbent assay, to anti-BHP14 than did the parental A-253 cells, and a
      partially revertant (C-10E ND) cell line had intermediate anti-BHP14 binding. BH
      activity in these cell lines was in the same rank order as antibody binding, but
      differences in immunoreactivity were less than differences in enzymatic activity.
      Our epitope-specific neutralizing antibody should be useful in the further
      characterization of BH.

PMID- 1378926
TI  - Epitope size, specificity and equilibrium constant for four monoclonal antibodies
      binding to the O:4 polysaccharide antigen of Salmonella serogroup B bacteria.
AB  - One rat (MAST 83) and three mouse (MAST 107, 108 and 112) monoclonal antibodies
      (mAbs) directed against Salmonella serogroup BO lipopolysaccharide (LPS) were
      characterized and found to bind to the O:4 epitope but recognizing different
      surfaces of the polysaccharide chain. The epitopes were defined from the combined
      results of: (i) binding specificities in enzyme immuno assay (EIA) against
      chemically defined LPS and glycoconjugates; (ii) studies of affinity constants in
      Farr-assay for binding to oligosaccharides purified from LPS, or chemically
      synthesized; and (iii) knowledge of the conformation of the O-polysaccharide
      chain of Salmonella BO bacteria. Two of the antibodies, MAST 83 and 108, bound to
      the O:4 epitope when present in the terminal non-reducing end as well as an
      intrachain determinant of the O-polysaccharide, whereas MAST 107 and 112 bound
      only to the O:4 epitope when present as an intrachain determinant. The
      equilibrium constants (K values), determined for binding of the mAbs and a Fab
      fragment isolated from one of them to a 125l-labelled tyramine-derivative of a
      Salmonella BO dodecasaccharide, were: 4.3 x 10(5) (MAST 83), 1.0 x 10(5) (MAST
      107), 1.3 x 10(5) (MAST 107 Fab), 4.5 x 10(4) (MAST 108) and 1.9 x 10(5) l/mol
      (MAST 112). The results suggest that each epitope encompasses the O:4 specifying
      D-abequosyl residue together with different numbers of saccharides varying in
      size from di- to tetrasaccharides from the linear backbone chain. The antibodies
      also bind to different surfaces of the O-polysaccharide chain as suggested by its
      conformation.

PMID- 1378927
TI  - Variable regions of antibodies to synthetic polypeptides--III. Antibodies arising
      in response to administration of anti-idiotope.
AB  - Antibodies elicited by the synthetic polypeptide antigen (T,G)-A-L are directed
      against two distinct epitopes. The majority of antibodies bind to a GT containing
      epitope and bear an idiotope defined by monoclonal antibodies I7 and I9. In this
      study, we have examined the effect of in vivo administration of the I7 and I9
      antibodies to mice. Administration of anti-idiotope elicits anti-(T,G)-A-L
      antibodies in all strains of mice tested, including genetic non-responders to
      (T,G)-A-L. These antibodies bind to GT and express the idiotope. Additionally,
      idiotope expressing antibodies that fail to bind to antigen are also produced.
      Monoclonal anti-(anti-idiotope) antibodies were made. One antibody bound to (T,G)
      A-L, the other did not. Sequence analysis was performed and the V-regions of
      (T,G)-A-L binding antibodies were compared to those of the antibody that failed
      to bind antigen. Both sets of antibodies are derived from the same germline V
      genes as the anti-(T,G)-A-L antibodies. These results have implications for
      understanding the nature of network regulation of the immune system and for those
      attempting idiotypic vaccination.

PMID- 1378928
TI  - Hamster female protein binding to chromatin, histones and DNA.
AB  - Hamster female protein (FP) is a member of the family of proteins known as
      pentraxins which share amino acid sequence homology, cyclic pentameric structure
      and calcium-dependent binding to ligands. Other members of this family include C
      reactive protein (CRP) and serum amyloid P component (SAP), and most species
      synthesize both CRP and SAP. FP is unusual in that it is apparently the only
      pentraxin produced in hamsters, it is under hormonal control and it shares
      binding characteristics with both CRP and SAP. CRP has been defined and isolated
      by its calcium-dependent binding to pneumococcal C-polysaccharide via
      phosphocholine (PC) residues. SAP has been isolated by calcium-dependent binding
      to agarose. FP binds to both PC and agarose. Recently, both SAP and CRP have been
      found to bind to chromatin in a calcium-dependent manner and involvement of these
      proteins in the clearance of nuclear material has been proposed. In this paper we
      test whether FP shares the ability to bind to chromatin and histones, and compare
      its relative avidities for these ligands. Similar to CRP, FP bound to histones H1
      and H2A, and chromatin. FP shared with SAP the ability to bind to DNA. However,
      FP binding was inhibited by PC for all ligands, whereas SAP binding was not. FP
      and SAP also failed to compete with each other for binding to DNA. By cross
      inhibition FP bound much less well to PC than CRP, but was a very effective
      inhibitor of CRP binding to H2A. These studies demonstrate that chromatin and
      histone binding are conserved among these pentraxins. The role of the proposed PC
      binding site in these binding reactions is discussed.

PMID- 1378929
TI  - Primary B-cell response to neuropeptide Y and bovine pancreatic polypeptide.
AB  - An analysis of the murine primary response to protein epitopes has been made with
      two small highly structured proteins, neuropeptide Y (NPY) and bovine pancreatic
      polypeptide (BPP), both of 36-amino acid residue length and containing helical
      structures. A group of cell lines producing monoclonal IgM antibody have been
      prepared consisting of six anti-NPY and two anti-BPP. The VH nucleotide sequences
      have been determined and characterized as germ-line either by identity to
      established germ-line sequences or by inference from the germ-line character of
      the D and JH segments. The intrinsic association constants for the homologous
      ligands have been estimated to range from 10(4) to 10(7) M-1 based on competitive
      ELISA. No severe restriction in the utilization of VH families, D segments or JH
      segments appears to be involved in this response. Among the eight cell lines,
      three VH families were represented as well as all three families of D segments
      and all of the JH segments, although some preference for JH3 was indicated. The
      length of the N(D)N sequences was also not subject to restriction, ranging from 9
      to 29. Two unusual features of the CRD3s were noted, one involving the
      utilization of an uncommon DSP2 segment and the other the apparent occurrence of
      a D-D fusion.

PMID- 1378930
TI  - Immunodominant structures in the aminoterminal portion of human interferon alpha
      1.
AB  - The analysis of the antigenic structure of human interferon (IFN)-alpha 1 with a
      panel of monoclonal antibodies revealed four immunodominant regions. Three of
      them, recognized by 12 of 14 antibodies were mapped into the aminoterminal
      portion of IFN-alpha 1 around residues 31-38, 43-53 and 63-85. The region 31-85
      proved important also for the antiviral and antiproliferative activity of the IFN
      alpha 1 molecule. The antibody recognizing the sequence around residues (54)63-67
      also inhibited the cellular binding of IFN-alpha 1 to the high-affinity
      receptors.

PMID- 1378931
TI  - Immunochemical analysis of a snake venom phospholipase A2 neurotoxin, crotoxin,
      with monoclonal antibodies.
AB  - Crotoxin is the major neurotoxic component of the venom of the South American
      rattlesnake, Crotalus durissus terrificus. The crotoxin molecule is composed of
      two subunits: a basic and weakly toxic phospholipase A2 (PLA2) called component-B
      (CB), and an acidic, nonenzymatic and nontoxic subunit called component-A (CA).
      Crotoxin exists as a mixture of several isoforms (or variants) resulting from the
      association of several subunit isoforms. We prepared monoclonal antibodies (MAbs)
      against each isolated subunit. Six anti-CA MAbs and eight anti-CB MAbs were
      tested for their cross-reactivities with each subunit and with other toxic and
      nontoxic PLA2s. Four of the six anti-CA MAbs cross-reacted with CB, whereas only
      one of the eight anti-CB MAbs cross-reacted with CA. Two anti-CB MAbs were found
      to cross-react with agkistrodotoxin, a single chain neurotoxic PLA2 purified from
      the venom of Agkistrodon blomhoffii brevicaudus. We determined the dissociation
      constants of each MAb for CA and CB isoforms and their capacities to neutralize
      the lethality and to inhibit the catalytic activity of crotoxin. We defined three
      epitopic regions on CA and four on CB, and used a schematic representation of the
      two subunits to characterize these epitopic regions with respect to: (1) the
      "toxic" and the "catalytic" sites of CB, and (2) the zone of interaction between
      the two subunits. We propose three-dimensional structures of the crotoxin
      subunits in which we localize amino acid residues that might be involved in the
      epitopic regions described here.

PMID- 1378932
TI  - Immune recognition of a molecule naturally presented as a monomeric or an
      oligomeric structure: the model of the human chorionic gonadotropin alpha
      subunit.
AB  - The immune recognition of a molecule naturally presented as a monomeric or an
      oligomeric structure is analyzed using the human chorionic gonadotropin alpha
      subunit (hCG-alpha) as a model. Indeed, hCG-alpha circulates as either a free
      subunit or combined to the beta subunit (hCG-beta) to form the dimeric hCG
      hormone. A T cell study was performed in BALB/c (H-2d) mice which were found to
      be high responders to hCG-alpha. Mice were immunized with the free hCG-alpha or
      the dimeric hCG alpha/beta, and their lymph node cells were challenged in vitro
      with either alpha subunits from different species, hCG or peptides spanning the
      entire primary structure of hCG-alpha. Proliferation and IL-2 assays demonstrated
      that hCG-alpha-primed lymph node cells responded equally well to hCG-alpha and
      hCG alpha/beta, suggesting that both the free and combined hCG-alpha subunits are
      processed in a similar way. Among the various synthetic peptides used, only those
      mimicking the hCG-alpha(59-92) C-terminus portion were able to stimulate hCG
      alpha-primed lymph node cells, demonstrating that this region contains
      immunodominant T cell recognition site(s). The hCG-alpha(23-43) and (32-59)
      peptides, although incapable of stimulating T cells primed with hCG-alpha,
      elicited a T cell response when used as immunogens. These regions encompassed
      cryptic epitopes which were not generated during hCG-alpha processing in H-2d
      mice. The T cell epitopes of hCG-alpha above described as immunodominant or
      cryptic on the free alpha subunit, had similar characteristics when the
      alpha/beta dimer was used as the immunogen. In contrast, T cells primed with
      peptides mimicking immunodominant sites recognized differently the hCG-alpha and
      the hCG alpha/beta antigens. Moreover, the analysis of the B cell response to all
      the immunogenic hCG-alpha peptides indicated that they bear B and T cell epitopes
      as well. Antibodies elicited against the hCG-alpha(59-92) or (32-59) peptide were
      capable of recognizing the alpha subunit in its free form but not in the
      alpha/beta hCG dimer. Such study deserves attention for the comprehensive
      mechanisms of the immune response to hCG as well as for the design of anti-hCG
      vaccines.

PMID- 1378933
TI  - Auto-antibodies to human sperm basic nuclear proteins in infertile and
      vasectomized men: characterization of antigens and epitopes recognized by
      antibodies.
AB  - The sera of vasectomized men and of patients with immune infertility were used to
      study the antigens and epitopes of sperm nuclear proteins that bind antibodies in
      these sera. No reaction with sperm histones was observed except for one serum.
      P1, P2 protamines and pro-P2 protamines were recognized by auto-antibodies.
      Studies with peptides derived from P1 and P2 protamines and with mammalian
      protamines related to HP1 showed that antibodies are mainly specific for a folded
      protamine molecule, more especially antibodies from vasectomized men. These
      results disagree with the random coil model proposed for protamines by several
      previous works. A cross-reactivity between P1 and P2 protamines was observed only
      for the whole molecules and not for peptides derived from them. This observation
      suggests that the two classes of protamines, different in sequence, may have a
      similar folding and thereby may be functionally equivalent.

PMID- 1378934
TI  - Analysis of C5b-8 binding sites in the C9 molecule using monoclonal antibodies:
      participation of two separate epitopes of C9 in C5b-8 binding.
AB  - C5b-8 binding sites in C9 were examined using mAbs raised against C9. Among 16
      mAbs, two, designated P40 and X197, blocked C9-mediated EAC1-8 lysis. C9
      pretreated with the mAbs failed to bind to EAC1-8 at 4 degrees C. In addition,
      the mAbs became inaccessible to the C9 that had been incorporated into EAC1-8 at
      4 degrees C. These findings suggest that C9 binding to EAC1-8, but not its
      membrane spanning or polymerization, is blocked by mAbs. By immunoblotting
      analysis using alpha-thrombin proteolytic fragments derived from C9 [a N-terminal
      fragment of mol. wt 25,000 (C9a) and a C-terminal one of mol. wt 37,000 (C9b)]
      and tryptic fragments of C9 (mol. wts 53,000 (C9a') and 20,000 (C9b')), the
      epitopes of P40 and X197 were mapped to the N-terminal and C-terminal regions of
      C9b, respectively. Both P40 and X197 bound to the C9 polymerized with Zn2+ in the
      fluid phase, whereas X197 but not P40 reacted with the membrane attack complex
      (MAC) formed on membranes. The results suggest that two distinct epitopes are
      involved in C9 binding to EAC1-8, and behave in a different manner for globular
      C9 bound to EAC1-8 at 4 degrees C, C9 assembled in MAC, or poly-C9 induced by
      Zn2+. These mAbs may be useful in clarifying the conformational states of C9 and
      in analyzing the molecular interaction between C9 and its inhibitors.

PMID- 1378935
TI  - Examination of B lymphoid cell lines for membrane immunoglobulin-stimulated
      tyrosine phosphorylation and src-family tyrosine kinase mRNA expression.
AB  - Crosslinking of membrane immunoglobulin (mIg) on B cells induces two signal
      transduction pathways: protein tyrosine phosphorylation and phosphoinositide
      turnover. A panel of murine and human B cell-lines, representing different stages
      of B cell development, was examined for the presence of anti-immunoglobulin
      induced protein tyrosine phosphorylation. Of 10 B cell lines examined, only one,
      the human Raji cell line, had no detectably induced protein tyrosine
      phosphorylation. The pattern of proteins that were phosphorylated on tyrosine in
      response to mIg crosslinking differed somewhat in cell lines representing
      different stages of B cell development. Differences in the levels of constitutive
      phosphorylation of proteins were also observed between the cell lines. The
      identity of the tyrosine kinase(s) activated by membrane immunoglobulin ligation
      is not known. However, members of the src family of intracellular tyrosine
      kinases have been implicated as signal transduction molecules. As the tyrosine
      phosphorylation of proteins is a general phenomenon of signal transduction by
      membrane immunoglobulin, the tyrosine kinase(s) activated by it might be expected
      to be present in all cell lines in which the tyrosine phosphorylation signalling
      occurs. Therefore we examined these B cells for expression of mRNAs encoding the
      eight known src-like tyrosine kinases. Surprisingly, all eight kinase mRNAs were
      expressed in at least some of the B cell lines examined. The expression pattern
      of the fyn, hck, and lck genes suggests that expression of these kinases may be
      developmentally regulated in the B cell lineage. Three of the kinases, p55blk,
      p53/p56lyn and p60src, were detected in all 10 B cell lines. Whereas the src gene
      shows a ubiquitous pattern of expression, the expression of the blk and lyn genes
      is mostly restricted to cells of hematopoietic origin, and more especially B
      lymphoid cells. Thus, p55blk and p53/p56lyn may be particularly good candidates
      for the membrane immunoglobulin-activated tyrosine kinase.

PMID- 1378936
TI  - Fine specificity of the murine antibody response to HIV-1 gp160 determined by
      synthetic peptides which define selected epitopes.
AB  - In this report, we assess the humoral immune response in inbred strains of mice
      immunized with baculovirus-derived recombinant HIV-1 gp160 (rgp160). Six inbred
      strains of mice were each immunized with two different concns (5 and 50
      micrograms) of rgp160, and the antibody response to rgp160 and synthetic peptides
      which define distinct gp160 epitopes was examined. Within a given inbred strain
      of mice, no significant difference in antibody titers to gp160 was observed in
      those groups receiving either 5 or 50 micrograms of rgp160 per injection.
      Following three immunizations with rgp160, differences in anti-gp160 titers were
      observed among the various inbred strains; however, these differences became less
      apparent after additional injections with rgp160. In addition, each mouse strain
      exhibited a unique reactivity pattern to seven gp160 epitopes defined by
      synthetic peptides. Multiple injections with rpg160 were required to induce
      responses to certain gp160 epitopes. The observed differences in the fine
      specificity of the humoral immune response to distinct gp160 epitopes among the
      six inbred strains suggest a genetic basis for regulating the antibody response
      to these epitopes. This apparent regulation can be overcome by multiple
      injections with rgp160.

PMID- 1378937
TI  - Characterization of T cell epitopes on the envelope glycoprotein of simian
      retrovirus 1 and 2 (SRV-1 and SRV-2) in several mouse strains.
AB  - Various mouse strains were immunized with either SRV-1 or SRV-2 virus adsorbed on
      alum. Seven to 14 days later spleen cells were removed, and spleen cells were
      cultured with varying amounts of SRV-1 virus and SRV-2 virus, or varying amounts
      of selected SRV-1 and SRV-2 synthetic envelope peptides to determine their
      ability to initiate T cell proliferative responses. Our studies demonstrated that
      all mouse strains tested gave strong proliferative responses with SRV-2 virus. In
      contrast, SRV-1 virus induced T cell proliferative responses only in H-2k mouse
      strains. This apparent major histocompatibility complex (MHC)-restriction of SRV
      1 virus-induced T cell proliferation correlates with the increased pathogenicity
      of SRV-1 virus in rhesus monkeys. The SRV envelope peptide 233-249 which is
      shared by both SRV-1 and SRV-2 virus initiates strong proliferative responses in
      both SRV-1 and SRV-2 virus immunized mice. The SRV-2 envelope peptide 96-102
      initiates significant proliferative responses in SRV-2 immunized mice, and
      constitutes both a T and B cell epitope. The SRV-2 envelope peptide 127-152 has a
      70% homology with the C-terminal region of SRV-1 peptide 142-167. The ability of
      SRV-2 peptide 127-152 to initiate T cell proliferation in SRV-1 virus immunized
      mice and the failure of the SRV-1 peptide 142-162 to initiate proliferation
      suggests that the region encompassing residues 160-167 must represent a T cell
      epitope in mice immunized with SRV-1 virus.

PMID- 1378939
TI  - Increased fetal hemoglobin in patients receiving sodium 4-phenylbutyrate.

PMID- 1378938
TI  - Nitric oxide synthase activity in infantile hypertrophic pyloric stenosis.
AB  - BACKGROUND: Hypertrophic pyloric stenosis is a common infantile disorder
      characterized by enlarged pyloric musculature and gastric-outlet obstruction. Its
      physiopathologic mechanism is not known, but a defect in pyloric relaxation
      (pylorospasm) has been postulated. Nitric oxide is a mediator of relaxation in
      the mammalian digestive tract, raising the possibility that pylorospasm could be
      caused by a defect in nitric oxide production. Since neuronal nitric oxide
      synthase and NADPH diaphorase are identical, we used the NADPH diaphorase
      histochemical reaction to study the distribution of nitric oxide synthase in
      pyloric tissue from patients with infantile hypertrophic pyloric stenosis.
      METHODS: We studied pyloric tissue from nine infants with infantile hypertrophic
      pyloric stenosis and seven control infants and children. Cryostat sections were
      processed for NADPH diaphorase histochemical analysis. A polyclonal tau antiserum
      was used to identify the enteric nervous system by immunohistochemical methods.
      RESULTS: NADPH diaphorase activity was restricted to the enteric nervous system
      and blood vessels. In the pyloric tissues from the control patients, intense
      diaphorase activity was present in the nerve fibers of the circular musculature,
      in the neurons and nerve bundles of the myenteric plexus, and in some nerve
      fibers of the longitudinal musculature. In the pyloric tissues from patients with
      infantile hypertrophic pyloric stenosis, the enteric nerve fibers in the
      hypertrophied circular musculature were enlarged and distorted and did not
      contain diaphorase activity, whereas the activity in the myenteric plexus and the
      longitudinal musculature was preserved. CONCLUSIONS: We suggest that a lack of
      nitric oxide synthase in pyloric tissue is responsible for pylorospasm in
      infantile hypertrophic pyloric stenosis.

PMID- 1378940
TI  - Characterization of immobilized anti-CD3 antibody-activated T lymphocytes for use
      in adoptive immunotherapy of patients with brain tumors.
AB  - Large numbers of T lymphocytes were successfully cultured for use in adoptive
      immunotherapy using immobilized anti-CD3 antibody. This method allows more than
      1.5 x 10(10) T lymphocytes to be cultured within 2 weeks from only 20 ml of
      blood. Proliferated T lymphocytes were less cytotoxic than lymphokine-activated
      killer cells induced with a high dose of interleukin-2, but were more specific
      for autologous tumor cells as determined by cold target competition. Signal
      transduction of anti-CD3 antibody induced a population of CD8 positive cells,
      i.e. cytotoxic T lymphocytes. Adoptive immunotherapy using autologous lymphocytes
      requires a sufficient number of lymphocytes and high induced cytotoxic activity.
      This method is promising for clinical adoptive immunotherapy of patients with
      brain tumors.

PMID- 1378941
TI  - Accessory middle cerebral artery and duplication of middle cerebral artery-
      terminology, incidence, vascular etiology, and developmental significance.
AB  - A series of 455 bilateral carotid angiographies included 14 accessory middle
      cerebral arteries (Acc-MCAs) and seven duplication of middle cerebral arteries
      (Dup-MCAs). The branching patterns of Dup-MCA could be classified as "direct
      bifurcation" from the internal carotid artery, since most lacked the essential
      bifurcation or trifurcation at the distal end of the M1 portion. On the other
      hand, Acc-MCAs are probably residual congenital arteries. These anomalous MCAs
      were apparently associated with epilepsy. Five Acc-MCAs were associated with
      anterior communicating artery aneurysm at the origin. In addition, a rare case of
      Dup-MCA with arteriovenous malformation at its origin was found.

PMID- 1378942
TI  - Prediction of motor function by magnetic brain stimulation in patients with
      intracerebral hematoma.
AB  - Corticospinal motor pathways were monitored with motor evoked potentials (MEPs)
      elicited by transcranial magnetic stimulation in 13 patients with radiologically
      confirmed hypertensive intracerebral hemorrhage and varying degrees of
      hemiparesis. The electromyographic responses of the thenar muscles were recorded.
      The motor weakness of the upper extremity was assessed at initial monitoring and
      3 months after hemorrhage, and correlated with changes in MEP. Absence of MEP in
      the acute stage indicated poor recovery of muscle strength. No false negative
      results were seen in our series. The presence of MEP in a completely hemiplegic
      patient predicted some recovery of motor function. The suppression of amplitude
      was more accurate than prolongation of latency in predicting the functional
      recovery. MEP monitoring of patients with hypertensive intracerebral hemorrhage
      in the acute stage can predict the outcome of motor function.

PMID- 1378943
TI  - Intramedullary subependymoma with neurofibromatosis--report of two cases.
AB  - Two cases of subependymoma in the cervical spinal cord associated with stigmata
      of neurofibromatosis are reported. Magnetic resonance (MR) imaging showed one
      tumor with a sharp margin, which was well-demarcated intraoperatively and was
      totally removed. MR imaging showed the other tumor with an irregular margin,
      which was partly invasive at operation. Subependymomas are rare in the spinal
      cord and these are the first reported associations with neurofibromatosis.

PMID- 1378944
TI  - Intracranial seeding following surgery for spinal cord astrocytoma--case report.
AB  - We report a case of intracranial dissemination developing approximately 6 months
      after partial removal of a spinal cord astrocytoma in a 40-year-old male. The
      clinical course and postmortem findings indicate that the tumor originated in the
      cervical cord and extended into the subarachnoid space, first the spinal canal
      and later intracranially. Spinal cord glioma dissemination through the
      cerebrospinal fluid is more common than previously considered and indicates a
      dismal prognosis. An aggressive approach, including radical surgery, entire
      neuraxis irradiation, and adjuvant chemotherapy, is suggested as the initial
      treatment for malignant spinal cord glioma to prevent subsequent dissemination.

PMID- 1378945
TI  - High cervical intradural lipoma--case report.
AB  - A rare high cervical intradural subpial lipoma unassociated with spinal
      dysraphism manifested by a slowly progressive myelopathy simulating Brown-Sequard
      syndrome in a 37-year-old male. The diagnosis was based on neuroradiological
      imaging. Intraoperative recording of somatosensory evoked potentials showed
      recovery of the prolonged N20 latency, indicating adequate decompression was
      achieved.

PMID- 1378946
TI  - Persistent trigeminal artery associated with brainstem infarct--case report.
AB  - A 47-year-old male presented with a sudden onset of right hemiparesis and
      numbness of the left face. Magnetic resonance imaging demonstrated a lacunar
      infarct in the ventral pons. Cerebral angiography demonstrated a persistent
      trigeminal artery (PTA) anastomosing the left internal carotid artery to the
      distal basilar artery. Bilateral vertebral arteries and the basilar artery below
      the PTA junction were extremely hypoplastic. The bilateral posterior
      communicating arteries were embryonic. The posterior fossa circulation was almost
      independent from the circle of Willis. The poor vascular supply to the posterior
      fossa probably caused the brainstem infarct.

PMID- 1378947
TI  - Coexistence of extracranial internal carotid artery aneurysm and multiple
      intracranial aneurysms--case report.
AB  - A rare case of extracranial internal carotid artery (ICA) aneurysm coexisting
      with intracranial multiple aneurysms in a 64-year-old female is reported. The
      three intracranial aneurysms were clipped uneventfully by two-stage craniotomies.
      The extracranial ICA aneurysm at the infratemporal region was excised through a
      high cervical route and ICA was reconstructed by an end-to-end direct
      anastomosis. Ours is the first case reported of extra- and intracranial aneurysms
      surgically treated successfully.

PMID- 1378948
TI  - Anomalous origin of the anterior cerebral artery and congenital skull dysplasia-
      case report.
AB  - A 37-year-old male had a ruptured anterior communicating artery aneurysm
      associated with an anomalous right anterior cerebral artery originating from the
      right internal carotid artery immediately distal to the ophthalmic artery and
      running between the optic nerves. The anomaly was associated with congenital
      skull dysplasia and other systemic bone anomalies, apparently an incomplete form
      of cleidocranial dysostosis. The aneurysm was successfully clipped with hematoma
      evacuation.

PMID- 1378949
TI  - Spontaneous epidural hematoma from a hepatocellular carcinoma metastasis to the
      skull--case report.
AB  - A rare case of acute epidural hematoma originating from a hepatocellular
      carcinoma metastasis to the skull in a 52-year-old male is reported. The skull
      metastasis and epidural hematoma were completely removed, but he died of large
      liver tumor. Histological examination of the removed tumor showed many sinusoid
      like blood vessels, which probably lead to hemorrhage and formation of epidural
      hematoma.

PMID- 1378950
TI  - Effects of human, rat and porcine galanins on cardiac vagal action and blood
      pressure in the anaesthetised cat.
AB  - Galanin (GAL) is distributed in sympathetic nerves in the cat, and exogenous GAL
      inhibits cardiac vagal action and lowers blood pressure in this species. This
      study on anaesthetised cats compares the effects on cardiac vagal action and
      blood pressure of human, rat and porcine GAL. Human GAL has only recently been
      sequenced. It is of particular interest as it is not C-terminally amidated,
      unlike porcine and rat GAL. Many regulatory peptides require a C-terminal amide
      group for their action. However, human GAL showed similar biological activity to
      the other (amidated) GALs here. Omission of a single amino acid (Ser6) from rat
      GAL significantly attenuated both cardiovascular actions studied here.

PMID- 1378951
TI  - Immunologic identification of Na/Ca exchange protein in rat brain synaptic plasma
      membrane.
AB  - Polyclonal antibodies raised against partially purified dog cardiac Na/Ca
      exchanger react with cardiac sarcolemmal proteins of 160, 120 and 70 kDa on SDS
      PAGE. Using the same specific antiserum, we detected three prominent
      immunoreactive bands of about 150, 120 and 70 kDa on immunoblots with rat
      forebrain synaptic plasma membrane proteins. These data indicate that the Na/Ca
      exchange protein in rat brain synaptic plasma membrane is structurally and
      antigenically similar to the exchange protein in dog cardiac sarcolemma.

PMID- 1378952
TI  - 5-Hydroxytryptamine, substance P and thyrotropin-releasing hormone synapses in
      the intermediolateral cell column of the rat thoracic spinal cord.
AB  - Serotonin-, substance P-, and thyrotropin-releasing hormone-immunoreactive
      profiles were studied in the intermediolateral cell column at the thoracic level
      of the rat spinal cord with light- and electron-microscopic immunocytochemistry.
      For each transmitter, a dense immunoreactive deposit was observed with the light
      microscope. At ultrastructural level, morphologically identified synapses
      amounted to 47% of all serotonergic varicosities, to 49% for substance P and 50%
      for thyrotropin-releasing hormone. Synapses appeared both symmetrical and
      asymmetrical. In each case, these synapses were mainly axodendritic (98%). These
      synaptic connections could mediate the physiological influence of these 3
      substances in the spinal cord on the cardiovascular system.

PMID- 1378954
TI  - Pain-less floating.

PMID- 1378953
TI  - Specificity and potency of N-methyl-D-aspartate glycine site antagonists and of
      mephenesin on the rat spinal cord in vitro.
AB  - The potency, specificity and reversibility of various presumed glycine site N
      methyl-D-aspartate (NMDA) antagonists was studied on neonatal rat spinal cord
      using the grease gap technique. 5,7-Dichlorokynurenate was the most potent and
      specific glycine site antagonist among the compounds tested. On the other hand
      mephenesin was a weak non-specific excitatory amino acid (EAA) antagonist;
      reduction of the response to NMDA was not reversed by D-serine. The EAA
      antagonist properties of mephenesin could explain its mode of action at the
      cellular level. The lack of effect of D-serine alone suggests that in our
      experimental conditions glycine sites on spinal neurones are occupied by an
      endogenous ligand.

PMID- 1378955
TI  - Urinary concentrations of beta core fragment of hCG throughout pregnancy.
AB  - OBJECTIVE: We sought to determine a reference range for urinary immunoreactive
      beta core fragment of hCG (beta C-hCG) in pregnancy, the ratio between beta C-hCG
      and intact hCG, and the earliest detectable rise of beta C-hCG in urine. METHODS:
      Urine was obtained from 741 pregnant women between 6-41 weeks' gestation, as well
      as from women undergoing donor insemination with timed ovulation peaks. RESULTS:
      The beta core fragment of hCG reached a maximum between 8-15 weeks, with a
      decrease between 20-29 weeks. The molar ratio of beta C-hCG to intact hCG was
      always greater than 1. CONCLUSION: In pregnancy, beta C-hCG concentrations
      increase in the urine in parallel to intact hCG but at a higher molar ratio,
      suggesting either placental production of beta C-hCG or enhanced metabolism of
      hCG to beta C-hCG in peripheral organs.

PMID- 1378956
TI  - The Charles F. Prentice Medal Award Lecture 1991: dopamine; a retinal
      neuromodulator.

PMID- 1378957
TI  - Corneal staining characteristics after sequential instillations of fluorescein.
AB  - Twenty-one healthy noncontact lens-wearing subjects were screened for the
      presence of corneal staining with fluorescein after sequential instillations of
      the vital stain (Phase I). These staining characteristics were further explored
      by monitoring the results of sequential instillations of fluorescein at 2-h
      intervals over a 12-h period (Phase II) and by patching 1 eye overnight and
      observing corneal staining after sequential instillations of fluorescein in the
      morning after patch removal (Phase III). In Phase II more eyes stained in the
      early morning. Throughout the day the most common staining areas were inferior
      and nasal. In Phase III, 9 of 12 patched eyes presented with fluorescein
      staining, as did 7 of the 12 unpatched eyes. Corneal staining after sequential
      instillations of fluorescein is more likely to be observed early in the day and
      is not reduced by overnight patching.

PMID- 1378958
TI  - [Successful treatment of hyperthyroidism simulating acute abdomen and psychosis].
AB  - A 49 years old female patient entered the surgical department because of
      epigastric and ileocoecal pains with the symptoms of acute abdomen. A surgical
      intervention was performed because of supposed appendicitis, but it was not
      verified. During the surgical observation the patient was confused and
      negativistic so she was transferred to the psychiatric department. Because of
      loss of 20 kg weight, high blood sedimentation and anaemia she was sent to our
      department with the suspicion of an organic disease. A moderate exophthalmos,
      glittering eyes and Graefe's sign was noted, therefore hyperthyroidism was
      diagnosed, which was proved by Kocher's blood picture, low serum cholesterol,
      extremely high T3 and T4 level, and iodine storage diagram. The antithyreotic
      treatment resulted a dramatic improvement in the extremely serious moreover
      hopeless case and after a long-term treatment the patient became symptom-free
      without complaints. Later because of regression of hyperthyreoidism and the
      growing nodular goitre the patient was treated on two occasions with radioactive
      iodine. At present the patient is in remission.

PMID- 1378959
TI  - Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of
      newborn infants.
AB  - Newborns are predisposed to neutropenia and thrombocytopenia during bacterial
      sepsis. The presence of peripheral cytopenias during overwhelming infection may
      be secondary to decreased hematopoietic growth factor production during states of
      increased demand. We therefore examined circulating levels of granulocyte-colony
      stimulating factor (G-CSF) and IL-3, production of G-CSF and IL-3 from
      unstimulated and stimulated mononuclear cells (MNC), expression of G-CSF and IL-3
      genes during unstimulated and stimulated conditions, and equilibrium and binding
      of G-CSF receptors on mature effector peripheral blood cells of adults and
      neonates. Serum from cord and adult peripheral blood contained negligible amounts
      of both G-CSF (less than or equal to 50 pg/mL) and IL-3 (less than or equal to 5
      pg/mL). Constitutive supernatant levels of G-CSF and IL-3 from cord and adult
      unstimulated MNC were also undetectable. However, there was a significant
      difference in G-CSF and IL-3 production from stimulated cord and adult MNC.
      Supernatants from stimulated adult MNC had significantly more G-CSF (p less than
      0.007) and IL-3 (p less than 0.02). Additionally, Northern blot hybridization and
      densitometry of autoradiographs demonstrated significantly more G-CSF and IL-3
      mRNA transcripts from adult than from cord MNC. Lastly, affinity, binding, and
      number of G-CSF receptors on cord and adult peripheral effector cells were equal.
      These data suggest that, during states of increased demand, cord MNC produce less
      G-CSF and IL-3 than do adult MNC and have an associated reduction in their
      respective mRNA transcripts. These findings may have implications in the
      pathogenesis of neonatal cytopenias during states of increased demand, such as
      sepsis.

PMID- 1378960
TI  - Selective impairment of taurine transport by cyclosporin A in a human placental
      cell line.
AB  - We investigated, using a human placental choriocarcinoma cell line as a model,
      the effects of the immunosuppressive drug cyclosporin A on several placental
      transport systems mediating the transfer of glucose and amino acids from mother
      to fetus. The results of the investigation show that the transport system
      responsible for the transfer of taurine is selectively impaired by the drug,
      whereas the other transport systems are either stimulated or not affected. The
      inhibitory effect of the drug on taurine transport appears to be due to
      interference with calmodulin-dependent processes because calmodulin antagonists
      such as W-7, calmidazolium, and CGS 9343B mimic the effects of cyclosporin A.
      FK506, another immunosuppressive drug that is currently undergoing clinical
      trials, does not have this inhibitory effect.

PMID- 1378961
TI  - Comparison of T cell functional changes during childhood with the ontogeny of
      CDw29 and CD45RA expression on CD4+ T cells.
AB  - The ontogeny of the peripheral blood mononuclear cells' responsiveness to various
      activators during childhood was studied and compared to the expression of CDw29
      and CD45RA molecules at the surface of CD4+ T cells. The results show that
      newborn peripheral blood mononuclear cells are characterized by a responsiveness
      to mitogens that is higher than that observed in adults, at least shortly after
      stimulation. This contrasts with a clear decreased response to CD2 and CD3 MAb at
      any time after stimulation. These functional characteristics correlate with a low
      density of CDw29 antigen on virtually all CD4+ T cells and a high density of
      CD45RA antigen on most CD4+ T cells at birth. These patterns of reactivity and
      phenotype are similar to those found among naive adult T cells. When ageing, the
      response to mitogens becomes rapidly similar to the adult's values, whereas the
      responses to CD2 or CD3 MAb are more gradually acquired. This slow rate of
      functional changes grossly parallels the increase of CDw29+ CD4+ and the decrease
      of CD45RA+ CD4+ T cell subsets. These changes finally lead to the
      immunophenotypic and functional characteristics that are typical of adult memory
      T cells. These results suggest that iterative antigenic stimulations both induce
      memory T cells and create the conditions to improve the overall immune
      competence.

PMID- 1378962
TI  - Human placental choline acetyltransferase activity at parturition.
AB  - Choline acetyltransferase (ChAT) activity measured in human placentae obtained
      during labour, or after labour of spontaneous onset, was significantly lower than
      that measured in placentae obtained before the onset of labour. The reduction in
      ChAT activity may partly account for the reduction in placental acetylcholine
      (ACh) content and release into maternal vessels at this time. When cycloheximide
      (10 micrograms/ml) was infused for 3 h into both fetal and maternal vessels of
      the perfused placental lobule, it did not significantly alter placental ChAT
      activity or ACh output from the fetal vessels, though it significantly reduced
      placental beta HCG release from the maternal side of the perfused lobule. These
      results suggest that regulation of placental ChAT activity at the time of human
      parturition may be due to endogenous modulators of its activity, rather than to
      acute changes in the synthesis of this enzyme.

PMID- 1378964
TI  - Intranephron distribution of glycine-amidinotransferase activity in rats.
AB  - Guanidinoacetic acid (GAA), a precursor of creatine, is an essential substrate
      for muscle energy metabolism, and synthesized by glycine-amidinotransferase
      (transamidinase) mainly in the kidney. Since the intranephron distribution of
      transamidinase activity has never been quantified yet, the purpose of this study
      is to provide evidence about the localization of transamidinase activity using
      microdissected individual nephron segments. Synthesized GAA was separated by HPLC
      and detected fluorometrically after reacting with 9,10-phenanthrenequinone.
      Results obtained were as follows. (1) Transamidinase activity was distributed
      only in the first (S1) and the second (S2) portion of the proximal tubule, S1
      being significantly higher than S2. (2) In S2, arginine and glycine were better
      substrates for GAA synthesis than canavanine and glycine. These results clearly
      indicate that GAA is synthesized in definite portions of the proximal tubule, and
      would be transported to the liver for further creatine production.

PMID- 1378963
TI  - [Computer-assisted speech training for aphasic patients--STACH and WEGE--in a
      self-help group].
AB  - Reported is our experience with two computer programmes for aphasic people
      (language loss after stroke). The STACH and WEGE programmes combine data banks of
      written language, pictures, and auditory speech output (delta modulation/Audicard
      300 E by Speech Design, Munich) using MS-DOS. Special attention is given to the
      social environment, the patients' families and the context of self-help groups,
      who show great interest in this new facility for speech-training.

PMID- 1378965
TI  - Tubular CO2 production from glutamine in the rat: segmental profile and
      modulation.
AB  - The present study was designed to test whether tubular carbon dioxide production
      from the carbon skeleton of uniformly 14C-labelled glutamine exhibits
      quantitative and qualitative segmental heterogeneity. Our results show that CO2
      production from glutamine in the proximal convoluted tubule (PCT) was dependent
      on substrate concentrations and is saturable at 10(-4) M of glutamine. Glutamine
      oxidation was demonstrable in all nephron segments examined. The PCT is the
      quantitatively predominant site of glutamine oxidation. Intermediate nephron
      segments, however, such as the thick ascending limb (MAL) and the distal
      convoluted tubule possess a significant capacity for glutamine oxidation,
      particularly when examined in terms of tubular protein content. Modulation of
      glutamine oxidation by extracellular pH was segment specific. Stimulation by
      acidosis and inhibition by alkalosis were observed in the PCT while carbon
      dioxide production from glutamine in the MAL was pH-insensitive. Glutamine
      oxidation was closely linked to sodium transport and greatly decreased by
      inhibition of Na-K-ATPase. In both the PCT and MAL, glutamine oxidation was
      inhibited by high extracellular potassium concentrations and in the PCT enhanced
      by extracellular hypokalemia. N-Ethyl maleiamide, an inhibitor of proton ATPase,
      led to almost complete cessation of CO2 production from the substrate in both PCT
      and MAL. Acetazolamide, an inhibitor of carbonic anhydrase, led to a partial
      reduction in carbon dioxide formation in the PCT, but did not affect glutamine
      oxidation in the MAL. We conclude that segmental qualitative heterogeneity
      characterizes oxidation of the carbon skeleton of glutamine with proximal
      segments showing the predictable effects of pH changes and carbonic anhydrase
      inhibition. The MAL appears to be nonmodulating.

PMID- 1378966
TI  - Effect of renal decapsulation on lithium excretion in the presence and absence of
      volume expansion.
AB  - The relationship between fractional sodium excretion (FENa) and fractional
      lithium excretion (FELi) was determined in Munich-Wistar rats with intact
      capsules (control, n = 16), and in rats with acute bilateral renal decapsulation
      (n = 16) during hydropenia and acute saline volume expansion. In response to
      volume expansion, the glomerular filtration rate increased significantly in both
      decapsulated and intact groups, but was similar in the two groups of rats at the
      same period. The FENa and FELi increased significantly from 0.49 +/- 0.10 and
      20.09 +/- 1.76% to 1.71 +/- 0.20 and 34.14 +/- 2.82% in control rats with volume
      expansion. In decapsulated rats, FENa and FELi were 0.17 +/- 0.03 and 11.64 +/-
      1.39% during control and increased to 1.04 +/- 0.21 and 26.23 +/- 1.17% during
      volume expansion. The FELi and FENa were significantly greater in control rats
      compared with decapsulated rats during both control and volume expansion periods.
      The lower FELi in bilateral renal decapsulation suggests reduced delivery of
      sodium from the proximal tubule.

PMID- 1378967
TI  - Isoproterenol infusion increases the maximal tubular capacity of phosphate
      reabsorption.
AB  - Isoproterenol, a beta-adrenoreceptor agonist, decreases urinary phosphate (Pi)
      excretion; however, plasma phosphate concentration also decreases. The purpose of
      the present study was to determine the effect of isoproterenol infusion on
      phosphate reabsorption with concomitant phosphate infusions and in the presence
      and absence of parathyroid hormone (PTH). Clearance experiments were performed on
      male Sprague-Dawley rats which were acutely thyroparathyroidectomized (TPTX) and
      successive infusions of phosphate (1, 2, and 3 mumol/min) were used to determine
      the maximal tubular capacity of phosphate reabsorption (TmPi) factored for the
      glomerular filtration rate (GFR) in four groups of rats. In the saline-infused
      control group the TmPi/GFR was 2.87 +/- 0.19 mumol/ml (n = 8). When isoproterenol
      was infused intravenously at a rate of 0.005 mg/kg/min, urinary cAMP excretion
      was significantly increased and the TmPi/GFR was 3.53 +/- 0.17 mumol/ml (n = 10,
      p less than 0.05). In the PTH-infused group (33 U/kg bolus followed by a
      sustaining infusion of 1 U/kg/min) TmPi/GFR was 1.69 +/- 0.15 mumol/ml (n = 9).
      Coadministration of isoproterenol and PTH significantly increased the TmPi/GFR to
      3.25 +/- 0.64 mumol/ml (n = 9). Basal cAMP excretion was similar in both groups.
      These results demonstrate that the stimulation of renal beta-adrenoreceptors by
      isoproterenol infusion markedly increases phosphate reabsorption and reverses the
      decrease in the maximal tubular capacity of phosphate reabsorption induced by PTH
      infusion.

PMID- 1378968
TI  - Effects of uninephrectomy and high protein feeding on lithium-induced chronic
      renal failure in rats.
AB  - Rats with lithium-induced nephropathy were subjected to high protein (HP)
      feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce
      glomerular hyperfiltration and further progression of renal failure. Newborn
      female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks
      and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another
      8 weeks. Corresponding non-lithium pretreated groups were generated. When
      comparing all lithium treated versus non-lithium-treated groups, lithium caused a
      reduction in glomerular filtration rate (GFR) without significant changes in
      effective renal plasma flow (as determined by a marker secreted into the proximal
      tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall
      in filtration fraction and an increase in fractional Li excretion. Lithium also
      caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP
      failed to accentuante progression of renal failure and in fact tended to increase
      GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused
      an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP
      caused a further rise in blood pressure in Li-pretreated rats. The results
      indicate that Li-induced nephropathy, even when the GFR is only modestly reduced,
      is associated with proteinuria and arterial systolic hypertension. In this model
      of chronic renal failure the decline in GFR is not accompanied by a corresponding
      fall in effective renal plasma flow, which may be the functional expression of
      the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of
      tubular fluid by the proximal tubules is reduced, leaving the distal delivery
      unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1378969
TI  - Comparisons of models of cortical necrosis with segmental infarction.
AB  - Sodium and water excretion were studied by standard clearance techniques in three
      experimental models where renal mass was reduced by superficial cortical necrosis
      (CN) or ischemic segmental infarction (SI). During hydropenia either CN or SI
      were able to conserve and regulate sodium to a very similar degree. After
      expansion of extracellular volume, CN reabsorbed less sodium and water than SI.
      In free-water clearance (CH2O) experiments, the 'apparent distal' sodium delivery
      was higher in CN than in SI, suggesting a decreased sodium and water reabsorption
      in the proximal tubules of juxtamedullary nephrons (JM). Both kidneys had similar
      CH2O when factored for inulin clearance but when CH2O was corrected for 'apparent
      distal' sodium delivery it was lower in CN than in SI, demonstrating an
      incapacity of JM to dilute urine. CN also showed less capacity to reabsorb free
      water than SI. Thus, the use of CN and SI within the same animal was useful to
      study functional differences between superficial and juxtamedullary nephrons. The
      present study also suggests that the kidney with superficial CN was unable to
      perform maximal urine dilution and concentration.

PMID- 1378970
TI  - 7th European Colloquium on Renal Physiology. Naples, Castel dell'Ovo, June 13-16,
      1992. Abstracts.

PMID- 1378971
TI  - The management of erectile dysfunction following spinal cord injury.

PMID- 1378972
TI  - [A case of apraxia and global aphasia without apraxia for axial body movement].
AB  - The case of a right handed 58 year old woman is presented who suffered an
      ischemic stroke after angiography following a vasospasm in the left internal
      carotid artery. The neuropsychological examination revealed global aphasia and
      severe apraxia for movements of the face and the extremities. However, the
      patient was able to carry out adequately axial movements to imitation and also to
      verbal command. These particular findings are discussed and explained within the
      context of the existing literature.

PMID- 1378973
TI  - [Responsibility and guilt from the psychiatric/psychotherapeutic viewpoint].
AB  - The sense of universal responsibility of the individual is based on a religious
      (in a pre- and overconfessional sense) relationship to a transpersonal whole. It
      is a prerequisite for the philosophical discourse on ethics. The special
      responsibility of the psychiatrist in his anthropological constructs, his
      concepts of illness and disease, and his method of treatment are discussed. The
      patient's being responsible (at least partly) for falling ill, his coping with
      his disease and impairment, his cooperation during treatment and also the
      pathology of inadequate guilt feelings and deficits are dealt with. Taking the
      blame as part of the human condition may be seen as an indicator of a mature
      development of a person.

PMID- 1378974
TI  - [Liaison psychiatric approach of the medical expert in criminal procedures].

PMID- 1378975
TI  - [Descriptive approach to the status of brief psychotherapy among psychotherapies
      offered at the Lausanne University Psychiatric Polyclinic].

PMID- 1378976
TI  - [The first interview and construction of the psychodynamic hypothesis].
AB  - The development of psychoanalitic short term therapy confirms the importance of
      the first interview for estimating the expectations of the patient and
      elaborating the first hypothesis. The therapist is immediately caught in the
      dynamics of pretransference and precountertransference. He depends upon the
      comprehension of his own emotional reactions to understand the actual affection
      and the nodal conflict. The psychodynamic hypothesis should be inferred from what
      both the patient and the therapist are saying and acting.

PMID- 1378977
TI  - [Recalling the acute psychotic experience].
AB  - In this study we have analysed the memory of the acute psychotic experience in
      chronic schizophrenics to evaluate the influence of memory on present
      symptomatology. We briefly examine the literature on this subject, then we
      describe some clinical cases trying to give a sense to the different way of
      "recovery", in schizophrenics. In particular we note that sensorial events of the
      acute psychotic experience have an important role in memory. Besides this study
      deepens some particular aspects of memory in schizophrenics.

PMID- 1378978
TI  - [Brief psychotherapy in the therapeutic arsenal of psychiatry].

PMID- 1378979
TI  - The contributions of the extracellular matrix to vascular form and function.

PMID- 1378980
TI  - Gold labelling of RNA in virus-induced mitochondrial vesicles in the sheep
      blowfly Lucilia cuprina.
AB  - Membranous vesicles are thought to be the replication site for viral RNA of many
      plant and animal viruses. A relatively rare site of virus-associated vesiculation
      is that of the mitochondrial outer membrane. In this study, virus-induced
      mitochondrial vesicles of the blowfly, Lucilia cuprina, were labelled with
      ribonuclease/gold and an antibody against double stranded RNA (anti
      polyinosinic:polycytidylic acid). Both methods showed the presence of RNA in the
      vesicles thus indicating they may be a site for viral RNA replication in Lucilia.

PMID- 1378981
TI  - Endothelium-derived nitric oxide synthase inhibition. Effects on cerebral blood
      flow, pial artery diameter, and vascular morphology in rats.
AB  - BACKGROUND AND PURPOSE: We determined the effects of inhibiting the production of
      cerebral endothelium-derived nitric oxide on pial artery diameter, cortical blood
      flow, and vascular morphology. METHODS: An inhibitor of endothelium-derived
      nitric oxide synthesis, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME),
      or an equivalent volume of 0.9% saline was infused into rats intra-arterially in
      a retrograde fashion via the right external carotid artery at a rate of 3
      mg/kg/min to a total dose of 190 mg/kg or intravenously at 1 mg/kg/min to a total
      dose of 15 mg/kg. Large pial arteries were continuously visualized through an
      operating microscope, and cortical cerebral blood flow was monitored by laser
      Doppler flowmetry. To localize areas of morphological interest, the protein
      tracer horseradish peroxidase was injected 15 minutes before termination of the L
      NAME infusion and the rats were perfusion-fixed 15 minutes later for light and
      electron microscopic analysis. RESULTS: Infusion of L-NAME significantly raised
      arterial blood pressure at both doses (for 190 mg/kg, from 103.2 +/- 3.4 to 135
      +/- 3.4 mm Hg; for 15 mg/kg, from 125 +/- 2.8 to 144.4 +/- 4.0 mm Hg). Pial
      arteries constricted within 10 minutes after the start of the intracarotid
      infusion to 40% of the preinfusion diameter, while cortical cerebral blood flow
      decreased to an average of 72.5% of that at baseline. Morphological abnormalities
      in the experimental rats included microvascular stasis and focal areas of blood
      brain barrier disruption to protein. Ultrastructural examination of cortical
      leaky sites revealed constricted arterioles with many endothelial pinocytotic
      vesicles and microvilli. CONCLUSIONS: These observations suggest that inhibition
      of endothelium-derived nitric oxide synthesis affects the relation between
      cerebral arterial diameter and cerebral blood flow and can lead to subtle
      cerebral vascular pathological changes consistent with focal brain ischemia.

PMID- 1378982
TI  - Immunotherapy for superficial bladder cancer. A developmental and clinical
      overview.
AB  - Superficial bladder cancer is one of the few solid human malignancies in which
      immunotherapy has been proved to be effective. Bacillus Calmette-Guerin was the
      vaccine which opened the door for this innovative approach. In an era of
      remarkable achievements in biotechnology, it is truly amazing that this throwback
      to the Stone Age of tumor immunology has not yet been replaced by a more (or
      equally) effective substitute. Potential candidates are already on the horizon
      and deserve a comprehensive evaluation. They must show not only that they are
      devoid of significant adverse effects but that they possess, beyond a doubt,
      superior antineoplastic activity. Even more remarkable is that one of the oldest
      vaccines still in use could emerge in a new role as an effective antineoplastic
      agent. Bacillus Calmette-Guerin has demonstrated an uncanny capacity for
      effectiveness as therapy for human diseases. Its protective effect against
      tuberculosis is well recognized, and its contribution to cancer therapy is widely
      known. A new and increasing repertoire has recently been presented: two separate
      groups of researchers have employed the vaccine successfully as a vehicle to
      express antigen-encoded genes from other pathogens. The exciting aspect of these
      recent studies resides in the demonstration that the altered vaccine is able to
      induce humoral and cell-mediated immune responses to the recombinant antigens,
      including the human immunodeficiency virus (HIV). Thus, BCG once more attracts
      enormous interest from the scientific community for its versatility and potential
      as a therapeutic agent.

PMID- 1378983
TI  - Immunotherapeutic alternatives in superficial bladder cancer. Interferon,
      interleukin-2, and keyhole-limpet hemocyanin.
AB  - Interleukin-2, IFNs, and TNF are biologic response modifiers that are part of an
      intricate network of interacting cytokines released during an immune response.
      Lack of sufficient endogenous cytokine activity secondary to the
      immunosuppressive effects of tumor growth may be overcome by direct, local
      application of biologic response modifiers or immunostimulants such as BCG or
      KLH. Bacillus Calmette-Guerin remains the most effective immunotherapeutic agent
      for superficial transitional-cell carcinoma. Although the mechanism of action is
      unknown, the weight of evidence suggests that local cytokine release is involved
      in the effector pathway. Recent data have shown that the local application of new
      single-agent immunotherapies can have an effect on superficial transitional-cell
      carcinoma and CIS similar to that of chemotherapeutic agents and nearly identical
      to that of BCG. But, unlike the situation with chemotherapy or BCG, these effects
      are attended by minimal or no toxicity. Chemotherapy and BCG failures have also
      shown responses to direct instillation of cytokines. Further understanding of the
      exact mechanism of action of these agents and of their interaction should lead to
      the optimal antitumor regimen with the least toxicity. Determining the degree of
      host immunoresponsiveness and which combination of cytokines or immunotherapeutic
      or chemotherapeutic agents is most effective for a specific tumor type is the
      challenge for the future.

PMID- 1378985
TI  - [Therapy of pancreatitis and pancreatic insufficiency].

PMID- 1378984
TI  - Immunohistochemical staining patterns of tenascin in invasive breast carcinomas.
AB  - Eighty-two cases of primary invasive breast carcinoma and adjacent "normal"
      mammary glands were examined immunohistochemically for tenascin expression and
      distribution. Formalin-fixed tissues pretreated with actinase were processed by
      the avidin-biotin complex method using anti-human tenascin monoclonal antibody
      (RBC1). In normal mammary glands, tenascin was distributed around the ducts and
      ductules but not around the acini. In carcinomas, a high incidence of tenascin
      positive cases (greater than 67%) was seen with various histological appearances,
      with the exception of lobular carcinoma where a low incidence was found (25%).
      Although intense staining was seen around cancerous foci when compared with
      normal mammary glands, tenascin was often expressed at cancer-mesenchymal
      junctions with dense fibrotic stroma, but not at junctions with active
      inflammatory change and a loose fibrotic stroma. Tenascin, expression is not an
      all-or-none marker for mammary malignancy and the staining pattern suggests
      either a role in stimulating cancer cells or a host defence mechanism accompanied
      by a desmoplastic response to them.

PMID- 1378986
TI  - [Welcome to quality assurance!. Interview by Carina Roxstrom].

PMID- 1378987
TI  - NADPH-diaphorase-positive cell populations in the human amygdala and temporal
      cortex: neuroanatomy, peptidergic characteristics and aspects of aging and
      Alzheimer's disease.
AB  - Previous studies have shown that nerve cells containing NADPH-diaphorase (NADPH
      d) are relatively resistant to various damaging processes. NADPH-d has been found
      to be colocalized with somatostatin (SOM) and neuropeptide Y (NPY) in neuronal
      populations of several forebrain regions. We have investigated the anatomical
      distribution, morphology and cell sizes of NADPH-d neurons in amygdala and
      temporal cortex in Alzheimer's disease (AD) compared to controls of different
      age. NADPH-d cells and fibers were present in layers II-VI of the cortex and in
      the white matter below the cortical mantle. In the amygdaloid complex, NADPH-d
      cells and processes were observed in almost all subnuclei. In the amygdala of
      aged controls, only insignificant atrophic alterations of NADPH-d neurons and
      fibers were seen. In AD, a moderate, but significant shift towards an increased
      number of medium-to small-sized neurons was measured in amygdala and cortex,
      indicating cell shrinkage during the course of the disease. However, there were
      no differences when comparing NADPH-d staining in amygdaloid subregions in AD
      cases that contained numerous neuritic plaques (i.e., accessory basal nucleus)
      with areas that were relatively free of lesions (i.e., lateral nucleus). Analysis
      of cell size of SOM- and NPY-immunoreactive cells revealed only slight atrophic
      changes during aging. In AD, however, a significant atrophy of somatostatin
      neurons in temporal cortex was found, whereas no further cell shrinkage was noted
      for NPY as compared to aged controls. Colocalization tests demonstrated a large
      overlap between NPY, SOM and NADPH-d in the amygdala, whereas a subpopulation of
      cortical SOM neurons, predominantly localized in upper layers, showed a lack of
      NADPH-d. Our findings of a relative stability of a selective subclass of neurons
      during aging and AD support the hypothesis that cellular pathology may affect
      only specific neuronal populations while others might be spared.

PMID- 1378988
TI  - Novel eosinophilic inclusion in astrocytes.
AB  - Intracytoplasmic and brightly eosinophilic inclusions within neuroglias are
      reported in a patient with Aicardi's syndrome. Most inclusion-bearing neuroglias
      were protoplasmic astrocytes in the cerebral cortex. Compared with similar
      eosinophilic and intracytoplasmic inclusions in other studies using both light
      and electron microscopy, the inclusions in this report are regarded as being
      novel and not previously described. Ultrastructurally, the inclusions were
      composed of electron-dense granules and amorphous substances, and were not
      surrounded by a limiting membrane. They were numerous in the cerebral cortex,
      especially in part of the microgyrus, but absent in the deep cerebral white
      matter, subcortical nuclei, brain stem and the cerebellum. Therefore, they may be
      closely associated with brain malformation and congenital astrocytic dysfunction.
      They also suggested a functional difference in protoplasmic astrocytes
      themselves, according to the differentiation of related gray matter.

PMID- 1378989
TI  - Molecular and cellular responses of the corneal epithelium to wound healing.
AB  - The corneal epithelium responds rapidly to injury, repairing defects with a layer
      of cells that covers the denuded corneal surface and prevents infection and loss
      of vision. After a wound, reorganization of the remaining epithelial cells occurs
      over several hours, resulting in the formation of a migratory leading edge.
      However, expression of genes such as c-fos occurs within minutes of wounding.
      This early expression may be important for directing epithelial reorganization
      and the later mitotic burst. Our results show that receptors for epidermal growth
      factor are upregulated in the migratory cell population. Proliferation through a
      mitotic burst was observed in cells surrounding the original wound margin after
      36 hours. The interaction between gene expression and cell surface receptors for
      growth factors and cell proliferation suggests that wound healing occurs in a
      complex, but tightly controlled process in the corneal epithelium.

PMID- 1378990
TI  - Structural and functional significance of intermediate filament proteins in the
      human organ of Corti.

PMID- 1378991
TI  - Ovarian mucinous cystadenocarcinoma producing alpha-fetoprotein. A case report.
AB  - A 62-year-old woman with a complaint of abdominal distention underwent surgery to
      remove a tumor in her left ovary. The serum alpha-fetoprotein (AFP) level was
      4,130 ng/ml. Histologically, the tumor was diagnosed as a mucinous
      cystadenocarcinoma with a small area of solid proliferation of tumor cells. The
      cells of the latter part were shown immunohistochemically to possess AFP. We
      suppose that a part of the mucinous cystadenocarcinoma dedifferentiates and
      produces AFP.

PMID- 1378992
TI  - A role for the arachidonic acid cascade in fast synaptic modulation: ion channels
      and transmitter uptake systems as target proteins.
AB  - Recent evidence indicates that arachidonic acid (AA) and its metabolites play a
      fast messenger role in synaptic modulation in the CNS. 12-Lipoxygenase
      derivatives are released by Aplysia sensory neurons in response to inhibitory
      transmitters and directly target a class of K+ channels, increasing the
      probability of their opening. In this way, hyperpolarization is achieved and
      action potentials are shortened, leading to synaptic depression. Other types of
      K+ channels in vertebrate excitable cells have been found to be sensitive to
      arachidonic acid, lipoxygenase products, and polyunsaturated fatty acids (PUFA).
      In the mammalian CNS, arachidonic acid is released upon stimulation of N-methyl-D
      aspartate (NMDA)-type glutamate receptors. We found that arachidonic acid
      inhibits the rate of glutamate uptake in both neuronal synaptic terminals and
      astrocytes. Neither biotransformation nor membrane incorporation are required for
      arachidonic acid to exert this effect. The phenomenon, which is rapid and evident
      at low microM concentrations of AA, may involve a direct interaction with the
      glutamate transporter or its lipidic microenvironment on the outer side of the
      cell membrane. Polyunsaturated fatty acids mimic arachidonate with a rank of
      potency parallel to the degree of unsaturation. Since the effect of glutamate on
      the synapses is terminated by diffusion and uptake, a slowing of the termination
      process may potentiate glutamate synaptic efficacy. However, excessive
      extracellular accumulation of glutamate may lead to neurotoxicity.

PMID- 1378993
TI  - Very long-chain fatty acids in peroxisomal disease.
AB  - Fatty acids with from 24 to 28 carbon atoms (very long-chain fatty acids, VLCFA)
      are present in small amounts in all mammalian tissues. Even longer chain fatty
      acids with from 30 to 38 carbon atoms (ultra-long-chain fatty acids, ULCFA) are
      found in certain specialized tissues including retina, brain, and spermatozoa. In
      patients with inherited defects in peroxisomal structure and/or function, there
      is an accumulation of VLCFA in most tissues, while VLCFA and ULCFA levels are
      increased in brain. The most pronounced changes occur in those patients who have
      defects in peroxisomal assembly (Zellweger syndrome, infantile Refsum's disease,
      and neonatal adrenoleukodystrophy). In the brain of these individuals, ULCFA are
      distributed largely in molecular species of phosphatidylcholine with penta-, hexa
      , and heptaenoic acids. In contrast, patients with X-linked adrenoleukodystrophy
      have increased levels of phosphatidylcholine with monoenoic rather than polyenoic
      ULCFA. A defect in a peroxisomal VLCFA CoA synthetase or ligase has been reported
      for these patients, but assembly of their peroxisomes is apparently normal. We
      speculate that ULCFA are normal products of carbon chain elongation. We have
      confirmed this by demonstrating the elongation of [1-14C]hexacosatetraenoic acid
      (26:4n-6) by rat brain in vivo to a series of longer chain tetraenoic acids with
      carbon chain lengths up to 34. Elongation to ULCFA can occur as well in non
      neural tissues as shown by detection of labeled saturated and monoenoic fatty
      acids with up to 32 carbon atoms after incubation of normal and Zellweger
      syndrome fibroblasts with [2-14C] acetate. Increased labeling of VLCFA and ULCFA
      is observed in cells from patients with peroxisomal disorders. Our data suggest
      that ULCFA with up to at least 32 carbon atoms are formed normally, as a part of
      the elongation process in most mammalian tissues, and that control of carbon
      chain elongation is a major function of peroxisomes. Impairment of this function
      as occurs in peroxisomal disease results in the accumulation of VLCFA and ULCFA.
      The relative enrichment in normal tissues of ULCFA such as 32:6n-3 in ram and
      bull spermatozoa and 36:4n-6 in human and rat brain suggests a probable
      physiological role for this class of fatty acids in these tissues.

PMID- 1378994
TI  - GnRH agonists and prostate cancer.

PMID- 1378995
TI  - The incidence of atrial arrhythmias during inferior wall myocardial infarction
      with and without right ventricular involvement.
AB  - The atrial arrhythmia profile during inferior wall acute myocardial infarction
      (AMI) has not been systematically examined with respect to right ventricular (RV)
      involvement. To this end, 62 consecutive patients with first inferior wall AMI
      and no other conditions known to increase susceptibility for rhythm disturbances
      were studied by 24-hour Holter monitoring during the first and tenth day of
      infarction. Based on radionuclear ventriculography performed on day 2 of
      infarction, patients were allocated to two groups: group A--36 patients (58%)
      with right ventricular ejection fraction (RVEF) less than 40% (mean +/- SD, 31 +/
      6%) and group B--26 patients (42%) with normal (greater than 40%) RVEF (mean +/-
      SD, 47 +/- 5%). There were no significant differences between the two groups with
      respect to age, sex, or left ventricular (LV) function. In the group as a whole,
      ectopic activity in the different categories of atrial arrhythmias was
      significantly higher during the first day than on the tenth day of infarction.
      Comparing the two groups, 33 patients (92%) in group A had a mean hourly
      frequency of one or more atrial premature contractions (APCs) during the first
      day of infarction compared with 18 patients (69%) in group B (p less than 0.001).
      Atrial and supraventricular tachycardia were recorded more frequently in group A
      patients (16 of 36 [44%] versus 8 of 26 [31%]) as well as atrial fibrillation
      (AF) (7 of 36 [19%] versus 1 of 26 [4%]). Quantitative analysis showed a similar
      trend for a higher rate of ectopic events in group A patients. Ectopic activity
      was neither influenced by LVEF nor by age or sex.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1378997
TI  - Outward currents in longitudinal colonic muscle cells contribute to spiking
      electrical behavior.
AB  - Electrical events in longitudinal and circular muscles of the colon are
      different. Longitudinal muscles generate action potentials superimposed upon
      small depolarizations termed myenteric potential oscillations and circular
      muscles generate slow wave events that persist for several seconds. Differences
      between circular and longitudinal muscles may be related to the potassium
      channels these cells express. We have studied Ca(2+)-dependent and voltage
      dependent K currents of isolated longitudinal cells with the whole cell patch
      clamp technique. Test depolarizations positive to -40 mV yielded a transient
      inward current followed by a large sustained outward current. Blockade of the
      inward Ca2+ current reduced the amplitude of the outward current. Outward current
      was also reduced by tetraethylammonium (TEA; 1 mM), suggesting that a component
      of the outward current is Ca2+ dependent. After blockade of the Ca(2+)-dependent
      outward current, a voltage- and time-dependent component of outward current
      remained. The activation and inactivation properties and sensitivity to TEA and 4
      aminopyridine (4-AP) were characterized. The voltage-dependent outward current in
      longitudinal cells had different properties than the voltage-dependent K currents
      in circular muscle cells (i.e., more negative inactivation, less sensitivity to 4
      AP). TEA (1-5 mM) increased the amplitude and frequency of action potentials in
      intact longitudinal muscles; 4-AP (1 mM) had little effect on electrical activity
      of longitudinal muscles. The data suggest that differences in electrical behavior
      of the 2 muscle layers may be related to the expression of different species of K
      channels.

PMID- 1378996
TI  - Altered sulfate transport via anion exchange in CFPAC is corrected by retrovirus
      mediated CFTR gene transfer.
AB  - PANC-1 (a permanent epithelioid cell line initiated from a pancreatic carcinoma
      of ductal origin) and CFPAC (a ductal epithelioid cell line established from a
      cystic fibrosis patient with pancreatic adenocarcinoma) display sulfate transport
      via carrier-mediated anion exchange as supported by the following lines of
      evidence: 1) saturation kinetics, 2) inhibition by the anion exchange inhibitor
      4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and 3) substrate
      specificity. The DIDS-sensitive component of sulfate uptake is markedly inhibited
      by S2O3(2-) and MoO4(2-) but not by HAsO4(2-), H2PO4-, or gluconate-. Competitive
      inhibition of SO4(2-) uptake by extracellular Cl- (Cl-o) and stimulation of SO4(2
      ) efflux by Cl-o support the possibility that SO4(2-) transport occurs via a
      SO4(2-)-Cl- exchange mechanism. Inhibition of sulfate uptake and stimulation of
      sulfate efflux by extracellular HCO3- indicate that SO4(2-)-HCO3- exchange is an
      alternative mechanism for sulfate transport in these cells. Further support for
      SO4(2-) being transported via a typical anion exchanger is the stimulation of its
      uptake at low extracellular pH and high intracellular pH. Amphotropic viruses
      have been used by others (M. L. Drumm, H. A. Pope, W. H. Cliff, J. M. Rommens, S.
      A. Marvin, L.-C. Tsui, F. S. Collins, R. A. Frizzell, and J. M. Wilson. Cell 62:
      1227-1233, 1990) to transduce a functional cystic fibrosis transmembrane
      regulator (CFTR) cDNA into CFPAC, resulting in the PLJ-CFTR clones. Control
      clones (PLJ) were obtained by exposing CFPAC cells to control virus. In the
      present study, we report a striking 10-fold increase in the capacity of the DIDS
      sensitive component of the sulfate transporter in two PLJ-CFTR clones (which had
      been shown by others to express corrected Cl- channel activity) compared with
      CFPAC and two PLJ clones. Our findings indicate that expression of the CFTR gene
      from a retroviral vector, which confers normal Cl- channel activity in the PLJ
      CFTR pancreas epithelial clones, is capable of correcting a second aspect of the
      cystic fibrosis phenotype, altered sulfate transport via an anion exchange
      mechanism.

PMID- 1378998
TI  - Expression and regulation of the cystic fibrosis gene during rat liver
      regeneration.
AB  - Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are
      responsible for cystic fibrosis. The CFTR gene has recently been identified and
      encodes a 6.5-kb mRNA transcript. Recent observations showing that CFTR
      expression increases during differentiation of epithelial cells suggested that
      CFTR may also be regulated in the liver in response to partial hepatectomy (PH).
      We studied the expression of CFTR in rat regenerating liver and investigated the
      mechanisms that regulate CFTR RNA levels during a 120-h period after PH. Northern
      and slot-blot analysis revealed a liver-specific biphasic increase of CFTR mRNA
      levels, which peaks at 2 and 24 h post-PH. In contrast to these findings, the
      mode of regulation of the homologous gene MDR-1 showed a clearly different
      pattern. Nuclear run-on analysis demonstrated increased levels of CFTR
      transcription corresponding to the time points where an increase in CFTR message
      was observed. Similarly, the beta-actin gene, which increases transiently during
      liver regeneration, showed increased nuclear run-on activity 4 h posthepatectomy,
      indicating that the nuclei were functional. No increase of MDR-1 gene
      transcription was detected, confirming the previous finding that the increase in
      MDR-1 mRNA level in regenerating liver results from a post-transcriptional event
      such as message stabilization. This study indicates that expression of the CFTR
      gene is regulated during the regenerative process of the liver. The data also
      suggest that the increase in CFTR and MDR expression levels result from two
      distinct regulatory mechanisms.

PMID- 1378999
TI  - Carbachol modulates voltage sensitivity of calcium channels in bronchial smooth
      muscle of rats.
AB  - The role of voltage-dependent Ca channels in carbachol (CCh)-induced contraction
      of rat bronchus was investigated. Membrane depolarization and BAY K 8644, a Ca
      channel opener, significantly enhanced CCh-induced contractions. Nisoldipine, an
      organic Ca channel blocker, significantly inhibited the contractions. Cadmium, an
      inorganic Ca channel blocker, completely inhibited maintained contractions caused
      by CCh. These results suggested that the voltage-dependent Ca channels play an
      important role in sustained cholinergic contractions. This hypothesis was tested
      further by investigating the properties of single Ca channels of rat bronchus
      smooth muscle cells. We used 10 mM Ba as the charge carrier and BAY K 8644 to
      increase open times. The single-channel conductance was 16.8 pS. Steady-state
      open probability (NP(o)) increased steeply with membrane depolarization (e-fold
      for 4 mV). The primary effect of CCh (10 microM) on Ca channels was to shift the
      membrane potential at which NP(o) was half maximal from -34 to -43 mV without
      changing the steepness factor or maximal NP(o). This CCh-induced increase in
      NP(o) was not caused by depolarization, because the single-channel current
      amplitude was unchanged by CCh. We conclude that one of the mechanisms by which
      CCh opens Ca channels of rat bronchus smooth muscle is by shifting the activation
      curve in the hyperpolarized direction.

PMID- 1379001
TI  - Endothelial cGMP does not regulate basal release of endothelium-derived relaxing
      factor in culture.
AB  - Guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in single and cocultures
      of calf pulmonary arterial endothelial (CPAE) and rabbit pulmonary arterial
      smooth muscle cells (RPASM) was investigated to discover whether endothelial cGMP
      is involved in the feedback regulation of basally released endothelium-derived
      relaxing factor (EDRF). Endothelial cell-induced increases in smooth muscle cGMP
      levels were inhibited by competitive inhibitors of endothelial nitric oxide
      synthesis, NG-monomethyl-L-arginine and N omega-nitro-L-arginine, in both long
      term cocultures and short-term bioassay. Such treatment had no effect on
      endothelial content of cGMP. Coculture cGMP accumulation was stimulated (twofold
      increases) by endothelium-dependent vasodilators, bradykinin and acetylcholine.
      Bradykinin and acetylcholine did not elicit cGMP accumulation in single cultures
      of either smooth muscle or endothelial cells. To investigate the underlying
      mechanism(s) of dissociation in cGMP accumulation between cocultures and single
      endothelial cell cultures, the distribution profile of guanylate cyclase isoforms
      was determined by stimulating CPAE and RPASM cells with vasodilators activating
      selectively the soluble or particulate isoenzymes. Both nitrovasodilators, sodium
      nitroprusside and a putative EDRF, S-nitroso-L-cysteine, produced a 20-fold
      increase in cGMP content of RPASM cells only, having no effect on endothelial
      cells. Conversely, atriopeptin II caused 80-fold increases in endothelial cells.
      Exposure of the short-term bioassay system to 100 nM atriopeptin II, which caused
      60-fold increases in CPAE cGMP levels, did not affect basal EDRF-induced smooth
      muscle cell cGMP accumulation, suggesting that a cGMP-mediated negative feedback
      mechanism does not appear to be involved in the regulation of basally released
      EDRF in culture.

PMID- 1379000
TI  - Corelease of galanin and NE from pancreatic sympathetic nerves during severe
      hypoglycemia in dogs.
AB  - To determine whether norepinephrine (NE) and galanin are coreleased during reflex
      activation of the sympathetic nervous system by hypoglycemia, we administered
      insulin to halothane-anesthetized (0.8%) dogs and measured the spillover of NE
      and galanin-like immunoreactivity (GLIR) into pancreatic venous plasma. Insulin
      injection produced hypoglycemia [plasma glucose (PG) = 34 +/- 3 mg/dl] but did
      not activate pancreatic noradrenergic (delta pancreatic NE output = +20 +/- 130
      pg/min) or galaninergic nerves (delta GLIR output = +40 +/- 50 fmol/min). To
      determine whether more severe hypoglycemia would activate these nerves, insulin
      was administered to dogs infused with somatostatin (SS; 2.5 micrograms/min) to
      block the counterregulatory increase of glucagon secretion. SS reduced the
      glucagon response to hypoglycemia by greater than 90%, which allowed PG to
      decrease to 14 +/- 1 mg/dl. Pancreatic NE output increased by 470 +/- 140 pg/min
      (P less than 0.005); however, pancreatic GLIR output did not increase
      significantly (delta = +70 +/- 50 fmol/min). When SS was discontinued, pancreatic
      NE output increased by 490 +/- 200 pg/min (P less than 0.025), and GLIR output
      increased by an additional +160 +/- 70 fmol/min (P less than 0.025; total delta
      from baseline = +230 +/- 90 fmol/min, P less than 0.025), suggesting that SS may
      restrain pancreatic NE and galanin release. Pancreatic NE and GLIR spillover were
      also increased during severe hypoglycemia when ganglionic neurotransmission was
      partially impaired with hexamethonium but not when the neural pathway was
      interrupted by spinal cord transection. We conclude that NE and galanin are
      coreleased from pancreatic sympathetic nerves when these nerves are centrally
      activated during severe hypoglycemia in halothane-anesthetized dogs.

PMID- 1379002
TI  - Cytoplasmic dilution induces antidiuretic hormone water channel retrieval in toad
      urinary bladder.
AB  - Antidiuretic hormone (ADH) increases the osmotic water permeability (Pf) of the
      toad urinary bladder by insertion of water channels into the apical cell
      membrane. Transepithelial water flow (Jv) reduces Pf by inducing endocytosis of
      apical water channels despite continuous ADH stimulation. This phenomenon is
      termed flux inhibition. We wished to determine whether cytoplasmic dilution or
      transcellular Jv causes flux inhibition because both have been proposed
      previously as a primary regulatory mechanism for this process. Apical membrane
      endocytosis was quantified by monitoring the uptake of the fluid phase marker
      fluorescein isothiocyanate dextran (FITC-dextran). FITC-dextran fluorescence was
      monitored in Triton X-100 extracts of epithelial cells as the ratio of total
      tissue fluorescence compared with background fluorescence. The background was
      defined as cellular autofluorescence and nonspecific tissue staining due to the
      presence of small amounts of free fluorescein contaminating the FITC-dextran.
      FITC-dextran uptake measured under symmetric isotonic (220 mosmol/kgH2O)
      conditions in either the absence (1.0 +/- 0.4 SD; n = 14) or presence (1.3 +/-
      0.3; n = 4) of ADH was not statistically different from that of background. In
      contrast, flux inhibition induced by a 180 mosmol/kgH2O apical-to-basolateral
      osmotic gradient increased FITC-dextran uptake to 3.4 +/- 1.3 (n = 7). FITC
      dextran uptake was identical in bladders exposed to symmetric hypotonic (150
      mosmol/kgH2O) solutions during ADH (3.6 +/- 0.9; n = 6) or adenosine 3',5'-cyclic
      monophosphate (3.1 +/- 0.4 fold; n = 3) stimulation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1379003
TI  - Regional distribution of ECS in contractile and conductive elements of rat and
      rabbit heart.
AB  - By adaptation of recently developed quantitative microanalytic techniques, the
      size of the extracellular space (ECS) was measured regionally in the rat and
      rabbit cardiac conductive and contractile tissues. When inulin and sucrose were
      measured as extracellular markers in rabbit heart, the ECS in the
      atrioventricular (AV) node was found to be, respectively, 2.4 and 2.2 times
      larger than that of adjacent ventricular muscle. By use of inulin, the ECS in the
      rabbit His bundle was found to be 1.8 times larger than the adjacent ventricular
      tissue. Similarly, when inulin was used in rat, the ECS of the AV node, His
      bundle, right bundle branch, and right atrium was found to be, respectively, 2.5,
      1.9, 1.8, and 1.2 times larger than that of left and right ventricular muscle.
      Similarly, significant regional differences in ECS were also observed in rat
      heart with sucrose. By use of glucose as an ECS marker, these results also
      revealed a 2.5-2.9 times larger ECS in rat and rabbit AV node compared with
      contractile elements. In contrast, ATP content, measured as an intracellular
      marker, was the same in both AV nodal and ventricular muscle tissue from both rat
      and rabbit. These data demonstrate that there are significant regional variations
      in ECS within the cardiac conduction system. Collectively, the data obtained with
      all extracellular markers indicate that the size of the ECS of the conduction
      system is markedly larger than the adjacent contractile muscle.

PMID- 1379004
TI  - Analysis of pulmonary and systemic vascular responses to platelet-activating
      factor in the cat.
AB  - Pulmonary and systemic vascular responses to platelet-activating factor (PAF)
      were investigated in the anesthetized cat. Intravenous injections of PAF
      decreased arterial pressure, increased pulmonary arterial pressure, and caused
      small but significant decreases in right and left atrial pressures. A transient
      increase in cardiac output was followed by a secondary decrease, and heart rate
      was increased. Pulmonary vascular resistance (PVR) was increased, systemic
      vascular resistance (SVR) was reduced, and changes in PVR and SVR in response to
      PAF were blocked by the novel PAF receptor antagonist, BN 50730. Under constant
      flow conditions PAF dilated the hindlimb vascular bed in a dose-related manner,
      whereas in the pulmonary lobar vascular bed, PAF caused dose-related increases in
      perfusion pressure. Hindlimb and lobar vascular responses to PAF were blocked by
      BN 50730 in a selective manner, whereas cyclooxygenase inhibitors had no effect
      on responses to the phospholipid mediator. Hindlimb vasodilator responses to PAF
      were reduced by N omega-nitro-L-arginine in a dose that blocked the response to
      acetylcholine but did not decrease responses to prostaglandin E1 or
      nitroprusside. Increases in lobar arterial pressure in response to PAF were not
      altered by treatment with a thromboxane receptor antagonist, when the lung was
      perfused with a low-molecular-weight dextran solution, or when ventilation to the
      lobe was interrupted. These data suggest that the release of cyclooxygenase
      products, activation of thromboxane A2 receptors, cellular aggregation, release
      of leukocyte or platelet mediators, or changes in bronchomotor tone do not
      contribute to the pulmonary vasoconstrictor response to PAF and that the hindlimb
      vasodilator response to the phospholipid mediator is dependent in part on the
      release of endothelium-derived relaxing factor.

PMID- 1379005
TI  - Acute effect of 17 beta-estradiol on rabbit coronary artery contractile responses
      to endothelin-1.
AB  - We assessed the acute effect of 17 beta-estradiol on coronary artery constrictor
      responses to endothelin-1. 17 beta-Estradiol significantly shifted endothelin-1,
      calcium, or BAY K 8644 concentration-dependent contraction curves to the right in
      endothelium-denuded coronary arteries isolated from nonpregnant female rabbits.
      The -log 50% effective dose (ED50) of calcium in high KCl medium (100 mM) was 3.8
      +/- 0.11 in control and 3.2 +/- 0.1 and 2.8 +/- 0.12 after incubation with 17
      beta-estradiol (1 and 10 microM, respectively). The -log ED50 of BAY K 8644 (KCl
      15 mM) was 7.8 +/- 0.1 in control and 7.4 +/- 0.08 and 7.2 +/- 0.05 in the
      presence of 17 beta-estradiol (1 and 10 microM, respectively). The -log ED50 of
      endothelin-1 was 9.2 +/- 0.08 in control and 8.8 +/- 0.1, 8.4 +/- 0.07, and 8.1
      +/- 0.12 after incubation with 17 beta-estradiol (3, 10, and 30 microM,
      respectively). Similar results were obtained from coronary arteries of male
      rabbits. These increases of -log ED50 values were significant (P less than 0.05
      or 0.01). 17 beta-Estradiol and verapamil induced dose-dependent relaxation in
      both endothelium-intact or -denuded coronary arteries submaximally precontracted
      by endothelin-1. NG-monomethyl-L-arginine had no effect on relaxation induced by
      17 beta-estradiol, whereas it eliminated relaxation induced by acetylcholine in
      rings with an intact endothelium. These data suggest that 17 beta-estradiol
      attenuates the rabbit coronary artery contraction induced by endothelin-1 via an
      endothelium-independent mechanism, possibly by affecting calcium influx.

PMID- 1379006
TI  - Cerebral blood flow, blood volume, and brain tissue hematocrit during isovolemic
      hemodilution with hetastarch in rats.
AB  - The influence of isovolemic hemodilution with 6% hetastarch [hematocrits (Hct)
      ranging from 43 to 20%] on cerebral blood flow (CBF), cerebral red blood cell and
      plasma volumes, total cerebral blood volume (CBV), and cerebral Hct was examined
      in normothermic, normocarbic, halothane-anesthetized Sprague-Dawley rats. CBF was
      measured via the indicator-fractionation method ([3H]nicotine), red blood cell
      volume was measured using 99mTc-labeled red blood cells, while plasma volume was
      measured using [14C]dextran. Brain tissue was fixed in situ by microwave
      irradiation. All data plots (e.g., CBF vs. Hct) were fitted by linear regression
      methods. Hemodilution was associated with a progressive increase in forebrain CBF
      (from a fitted value of 78 ml.100 g-1.min-1 at Hct = 43%, to 171 ml.100 g-1.min-1
      at 20%). Cerebral plasma volume also rose, while red blood cell volume decreased.
      Total CBV (i.e., the sum of red blood cell and plasma volumes) increased in
      parallel with CBF (from 2.51 ml/100 g at Hct = 43 to 4.94 ml/100 g at Hct = 20%).
      This increase is larger than can be explained by a simple increase in the
      diameter of arterial/arteriolar resistance vessels and may be due to either
      capillary recruitment or to an increase in the volume of postarteriolar
      structures. Calculated cerebral tissue hematocrit decreased. The magnitude of
      this decrease was larger than the reduction in arterial Hct; the ratio of
      cerebral to arterial Hct decreased from 0.780 at an arterial Hct equaling 43% to
      0.458 at Hct equaling 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379007
TI  - The subscapularis muscle and its glenohumeral ligament-like bands. A
      histomorphologic study.
AB  - The subscapularis muscle and the distribution of its tendinous bands is of
      significance in the surgical management of the shoulder joint. This distribution
      pattern has not been previously described in detail. We feel that, in any
      anterior approach to the glenohumeral joint for fracture fixation, joint
      replacement, and soft tissue reconstruction, a thorough understanding of the
      distribution pattern of the subscapularis bands is essential. We examined the
      subscapularis muscles from five cadavers. Four sections from the lateral one-half
      of each muscle were custom-mounted and stained with Masson's trichrome. We found
      a consistent pattern in which the tendinous bands were evenly interspersed in the
      midportion of the muscle and condensed laterally into a single large, flat tendon
      in the superior two-thirds of the muscle. The inferior one-third remained
      muscular. Understanding this pattern should help the surgeon have confidence that
      he/she has obtained a more secure repair in procedures involving the
      subscapularis muscle.

PMID- 1379008
TI  - Antigenic diversity of Rickettsia conorii.
AB  - Analysis of seven strains designated as Rickettsia conorii for reactivity with a
      panel of 12 monoclonal antibodies to surface-protein epitopes of spotted fever
      group rickettsiae and by Western immunoblotting with standard serotyping sera
      revealed remarkable antigenic diversity. Rickettsial strains from France,
      Morocco, Ethiopia, Kenya, South Africa, India, and the USSR differed from one
      another in reactivity with at least one and as many as five monoclonal
      antibodies. Simko and Indian strains were similar to one another and differed
      substantially from other R. conorii strains. All seven strains reacted with three
      R. conorii-specific monoclonal antibodies. Western immunoblotting demonstrated a
      major 120-kD protein and a major 135-kD protein in all strains. The principal
      differences were the presence of a major undenatured 130-kD protein in all
      strains except Indian and Simko, which had an analogous protein of 124 kD.
      Immunodominant antigenically related, heat-denatured protein bands of 170 kD
      (Malish 7 strain), 175 kD (Manuel strain), and 190 kD (Kenya tick typhus, Indian,
      and Simko strains) were not detected in the M-1 and Moroccan strains. This
      antigenic diversity is greater than that previously reported for other spotted
      fever group rickettsial species, suggesting that R. conorrii is an older species
      than R. rickettsii with a longer period of time for evolutionary divergence.

PMID- 1379009
TI  - [Cardiorespiratory and microcirculatory effects following volume replacement
      using a new hydroxyethyl starch preparation].
AB  - Volume therapy is often necessary in cardiac surgery to maintain stable
      haemodynamics. Various different hydroxyethyl starch (HAES) solutions with
      different concentrations, mean molecular weights, and degrees of substitution are
      available for this purpose. In determining the ideal type of volume therapy, not
      only changes in macrohaemodynamics, but also the influence on microcirculatory
      blood flow have to be taken into account. The efficacy of a new 10% HAES 130/0.5
      solution was studied in cardiac surgery patients in comparison to a standard 10%
      HAES 200/0.5 preparation. METHODS. In patients scheduled for elective
      aortocoronary bypass grafting who had a pulmonary capillary wedge pressure (PCWP)
      of less than 4 mm Hg after induction of anaesthesia, either a new 10% HAES
      130/0.5 (n = 15) or a standard 10% HAES 200/0.5 solution (n = 15) was infused to
      double the reduced PCWP; 15 patients without volume therapy served as controls (n
      = 15). A two-channel laser Doppler skin blood-flux monitor was used to evaluate
      microcirculatory alterations. Measurements of laser Doppler flux (LDF) was
      simultaneously performed at the patient's forehead and forearm before and after
      volume infusion as well as during and after cardiopulmonary bypass (CPB). In
      addition, changes in gross haemodynamics were documented using a pulmonary artery
      catheter. Plasma viscosity and various laboratory parameters, including
      calculation of intrapulmonary right-to-left shunting (Qs/Qt), were also measured.
      RESULTS. Cardiac index (CI) increased in both volume groups (HAES 130: max. +38%;
      HAES 200: +55%). The increases in PCWP and CI were maintained at 40 min after
      volume infusion only in the HAES 200 patients. Systemic vascular resistance (SVR)
      decreased most markedly after infusion of HAES 200 (-34%; HAES 130: -18%). No
      further differences in gross haemodynamics could be seen after CPB. Plasma
      viscosity and colloid osmotic pressure increased in both HAES groups without
      significant differences. During the entire investigation period, pulmonary gas
      exchange (paO2) and Qs/Qt did not differ between the groups. Infusion of both
      HAES solutions resulted in an increase in LDF that was most pronounced after
      infusion of HAES 200 (forehead LDF: +81%; HAES 130: +18%) and was evident in the
      post-bypass period only in these patients (LDF: HAES 200: +82%; HAES 130: -20%;
      control: -43%). No correlation between LDF values and the other haemodynamic and
      laboratory parameters could be demonstrated. CONCLUSION. The improvement in
      macrohaemodynamics was of shorter duration after infusion of the new HAES 130
      solution than after standard HAES 200. Volume replacement with HAES 200 resulted
      in an increase in microcirculatory blood flow that was more pronounced and of
      longer duration than in the HAES 130 patients. Thus, HAES 130 seems to be less
      effective than HAES 200 for volume replacement; HAES 200 should be preferred in
      patients undergoing cardiac surgery.

PMID- 1379010
TI  - [New indications for gamma globulins].
AB  - Intravenous immunoglobulin (IV Ig) has been shown its therapeutic value in
      primary immunodeficiency diseases associated with a profound impairement of IgG
      mediated antibody production. In recent years its range of indications has been
      extended to some secondary immunodeficiency disorders such as chronic lymphocytic
      leukemia and children with symptomatic HIV infection IV Ig is also of value in
      cytomegalovirus infection in transplant recipients. The use of IV Ig in some
      immunoregulatory disorders, namely immune thrombocytopenic purpura and Kawasaki
      syndrome has also been proved. Preliminary studies suggests a benefit in
      myasthenia gravis, Guillain-Barre syndrome, polymyositis, chronic demyelinating
      diseases and steroid dependent asthma. Little is known about the mechanism of
      action of IV Ig in these immunoregulatory disorders. In sum, IV Ig has a few
      proved indications and many potential ones. Carefully controlled clinical trials
      are needed to determine the effectiveness of IV Ig in these conditions.

PMID- 1379011
TI  - Comparative pharmacology of kainate-stimulated single-channel activity in outside
      out patches is consistent with a multiplicity of non-NMDA receptors.

PMID- 1379012
TI  - MK-801 protects against amphetamine-induced striatal dopamine depletion in
      iprindole-treated rats, but not against brain serotonin depletion after p
      chloroamphetamine administration.

PMID- 1379013
TI  - Regional distribution to recovery of 5-HT levels after administration of
      "atrophins" MDMA and D,L-fenfluramine. Stereospecificity and comparison with 5,7
      dihydroxytryptamine.

PMID- 1379014
TI  - Neurotoxic amphetamine analogues: effects in monkeys and implications for humans.
AB  - A wealth of evidence has accrued over the last 20 years indicating that certain
      amphetamine analogues have the potential to damage central monoaminergic neurons.
      For example, amphetamine has been shown to be toxic to dopamine neurons, MDMA to
      serotonin neurons, and methamphetamine to both (Table 1). In rodents, the toxic
      effects of amphetamines appear to be limited to axon terminals, and regenerative
      sprouting tends to be the rule. By contrast, in primates, nerve cell bodies
      appear to be affected, and the deleterious effects of amphetamine derivatives
      tend to be longer lasting, and possibly permanent (Fig. 2). Although findings in
      animals are compelling, observations in humans are less clear. In particular, it
      remains to be determined whether amphetamine analogues damage central
      monoaminergic neurons in humans and, if they do, whether functional consequences
      ensue. Also, the mechanism by which amphetamines damage monoaminergic neurons
      remains to be defined. Further insight into these basic and clinical aspects of
      amphetamine neurotoxicity should enhance our understanding of central
      monoaminergic systems in normal brain function, and their role in the
      pathophysiology of neuropsychiatric disorders.

PMID- 1379015
TI  - Interaction of calcitonin gene-related peptides with pancreatic acinar cells and
      dispersed gastric smooth muscle cells.

PMID- 1379016
TI  - Selective release of somatostatin by calcitonin gene-related peptide and
      influence on pancreatic secretion.
AB  - Calcitonin gene-related peptide is a potent inhibitor of stimulated pancreatic
      exocrine secretion in vivo. The mechanism of this inhibitory action was studied
      in dogs and rats. The questions examined were: (1) is the inhibitory action of
      CGRP on pancreatic secretion mediated by somatostatin? (2) is the inhibition
      direct, via action on acinar cells, or indirect? and (3) is a neuronal mechanism
      involved, and, if so, by what pathway? In dogs with chronic pancreatic fistulae,
      CGRP caused significant inhibition of the outputs of pancreatic protein (63-68%)
      and of pancreatic bicarbonate (74-89%) and a simultaneous dose-related rise (40
      102 fmol/ml) in plasma somatostatin-like immunoreactivity. A similar degree of
      inhibition was found when exogenous somatostatin was infused to achieve similar
      levels of plasma somatostatin-like immunoreactivity. More direct evidence of
      somatostatin mediation of CGRP action was sought in conscious rats with
      pancreatic fistulae using a potent and specific monoclonal antibody to
      somatostatin. The latter studies suggest that CGRP has both a somatostatin
      dependent and a somatostatin-independent mechanism of action. In isolated rat
      acini, CGRP did not inhibit CCK-stimulated amylase release, suggesting that its
      in vivo action is indirect. In the isolated vascularly perfused rat pancreas,
      CGRP (10(-10)-10(-7) M) inhibited in a dose-dependent manner volume and protein
      output stimulated by a mixture of CCK-8 and secretin. The inhibitory action of
      CGRP was blocked by tetrodotoxin (10(-7) M) and by atropine (10(-7) M), but not
      by hexamethonium (10(-7) M). We conclude that CGRP action: (1) is partly
      explained by release of somatostatin; (2) is indirect; (3) is neurally mediated;
      and (4) involves cholinergic muscarinic neurons within the pancreas.

PMID- 1379017
TI  - Calcitonin gene-related peptide influence on central nervous system
      differentiation.

PMID- 1379018
TI  - Immunohistochemical localization of putative peptide neurotransmitters in the
      human trigeminal sensory system.

PMID- 1379019
TI  - Calcitonin gene-related peptide in human celiac/superior mesenteric and inferior
      mesenteric ganglia. Immunohistochemical localization and coexistence with
      substance P.

PMID- 1379020
TI  - Time course of capsaicin-evoked release of CGRP from rat spinal cord in vitro.
      Effect of concentration and modulations by ruthenium red.

PMID- 1379022
TI  - Evidence for an increase in the release of CGRP from sensory nerves during
      inflammation.

PMID- 1379021
TI  - Release of CGRP-like immunoreactivity from cultured sensory neurons.

PMID- 1379023
TI  - Mechanisms of action of the dilatory response to calcitonin gene-related peptide
      in guinea pig basilary artery.

PMID- 1379024
TI  - Involvement of CGRP in the control of acetylcholine-induced endothelium-dependent
      vascular relaxation.

PMID- 1379025
TI  - CGRP modulates nerve-mediated vasoconstriction of rat knee joint blood vessels.

PMID- 1379026
TI  - Spontaneous hyphema: an unusual complication of uveitis associated with
      ankylosing spondylitis.
AB  - Two patients with ankylosing spondylitis (AS) and recurrent uveitis had rubeosis
      iridis each with an episode of spontaneous hyphema. Rubeosis iridis has been
      reported to occur in some cases of uveitis, but it has not been seen in those
      associated with AS. We suggest that AS be included among the conditions that can
      lead to the development of rubeosis iridis, with consequent silent hyphema.

PMID- 1379027
TI  - T cells from normal and myasthenic individuals recognize the human acetylcholine
      receptor: heterogeneity of antigenic sites on the alpha-subunit.
AB  - The alpha-subunit of the nicotinic acetylcholine receptor is the major target of
      the autoimmune response in myasthenia gravis. We investigated the proliferative
      response of T cells from patients with myasthenia gravis and healthy volunteers
      to recombinant polypeptides of the human acetylcholine receptor including the
      full-length alpha-subunit (alpha 1-437). T cells from 20 (71%) of 28 patients and
      7 (37%) of 19 healthy volunteers responded in primary cultures. Subsequently,
      specific T-cell lines were established: CD4+, CD8-, UCHL1+, and major
      histocompatibility complex (MHC) class II-restricted. Using a set of fragments of
      the alpha-subunit, major antigenic sites could be localized on the extracellular,
      N-terminal part of the molecule as well as close to the C-terminus. The T-cell
      response was heterogeneous, both among different individuals and among T-cell
      lines from a single donor. These T cells did not cross-react with Torpedo
      acetylcholine receptor, which was previously used as a substitute for human
      muscle acetylcholine receptor, suggesting that the T cells had a bias for unique
      human sequences. A single antigenic fragment could be presented in the context of
      different MHC class II molecules, and different fragments could be presented in
      the context of the same MHC molecule. This supports earlier observations of
      considerable heterogeneity in dealing with acetylcholine receptor as an
      autoantigen on the level of both T cells and antigen-presenting cells. The data
      also demonstrate that acetylcholine receptor-specific T cells are present in the
      normal immune repertoire, and emphasize the role of immune regulation for
      maintaining a state of tolerance.

PMID- 1379028
TI  - Myelin basic protein peptides in urine.

PMID- 1379030
TI  - The effects of catalase gene overexpression on life span and resistance to
      oxidative stress in transgenic Drosophila melanogaster.
AB  - Oxygen free radicals and hydroperoxides have been postulated to play a causal
      role in the aging process, implying that antioxidant enzymes may act as longevity
      determinants. Catalase (H2O2:H2O2 oxidoreductase; EC1.11.1.6) is the sole enzyme
      involved in the elimination of H2O2 in Drosophila melanogaster; glutathione
      peroxidase being absent. A genomic fragment containing the Drosophila catalase
      gene was used to construct transgenic Drosophila lines by means of P element
      mediated transformation. Enhanced levels of catalase (up to 80%) did not prolong
      the life span of flies, nor did they provide improved protection against
      oxidative stress induced by hyperoxia or paraquat treatment. However, enhanced
      resistance to hydrogen peroxide was observed in the overexpressors.

PMID- 1379029
TI  - Dual staining of natural bacterioplankton with 4',6-diamidino-2-phenylindole and
      fluorescent oligonucleotide probes targeting kingdom-level 16S rRNA sequences.
AB  - A method for quantifying eubacterial cell densities in dilute communities of
      small bacterioplankton is presented. Cells in water samples were stained with
      4',6-diamidino-2-phenylindole (DAPI), transferred to gelatin-coated slides, and
      hybridized with rhodamine-labeled oligonucleotide probes specific for kingdom
      level 16S rRNA sequences. Between 48 and 69% of the cells captured on membrane
      filters were transferred to gelatin-coated slides. The number of DAPI-stained
      cells that were visualized with eubacterial probes varied from 35 to 67%. Only 2
      to 4% of these cells also fluoresced following hybridization with a probe
      designed to target a eukaryotic 16S rRNA sequence. Between 0.1 and 6% of the
      bacterioplankton in these samples were autofluorescent and may have been mistaken
      as cells that hybridized with fluorescent oligonucleotide probes. Dual staining
      allows precise estimates of the efficiency of transfers of cells to gelatin films
      and can be used to measure the percentage of the total bacterioplankton that also
      hybridize with fluorescent oligonucleotide probes, indicating specific
      phylogenetic groups.

PMID- 1379031
TI  - Fate and effects of the insecticide Dursban 4E in indoor Elodea-dominated and
      macrophyte-free freshwater model ecosystems: I. Fate and primary effects of the
      active ingredient chlorpyrifos.
AB  - The fate of the insecticide Dursban 4E (active ingredient chlorpyrifos) and its
      effect on crustaceans and insects was studied in indoor experimental freshwater
      ecosystems that intended to mimick drainage ditches. A single dose (simulating
      aerial drift) was applied to achieve nominal chlorpyrifos concentrations of 5 or
      35 micrograms/L. Two experiments were performed, one in which all model
      ecosystems were dominated by the macrophyte Elodea nuttallii, and one using
      systems devoid of macrophytes. In macrophyte-dominated systems, Elodea vegetation
      adsorbed a large proportion of the dose applied and hampered the mixing of the
      insecticide in the water (at least up till day 8). Only a small proportion became
      incorporated in the sediment. In open water systems the insecticide was rapidly
      mixed in the water, and the sediment played a very significant role as sink for
      chlorpyrifos. In both Elodea-dominated and open water systems 50% of the dose
      applied had disappeared on day 8 post-treatment. The rate of disappearance of
      chlorpyrifos was relatively rapid in water and macrophytes, and relatively slow
      in the sediment. Of the arthropods in the zooplankton Cladocera were more
      susceptible than Copepoda. Significant effects (p less than or equal to 0.05) on
      Cladocera occurred relatively late in Elodea-dominated systems (in week 4 post
      application) in contrast to open water systems (week 1), which is in accordance
      with the observed differences in the fate of chlorpyrifos. Daphnia pulex, D.
      longispina and Simocephalus vetulus recovered in the model ecosystems when
      chlorpyrifos concentrations were lower than 0.1-0.2 micrograms/L, which is in
      agreement with results of laboratory protocol tests performed with these
      cladocerans. Among the macroscopic Arthropoda the apparent order of
      susceptibility was amphipods greater than insects greater than isopods. The
      isopod Asellus aquaticus was more sensitive to the application of the insecticide
      than the closely related species Proasellus coxalis. In treated open water
      systems the latter even increased significantly in numbers. Cage experiments in
      the model ecosystems performed with several species of Arthropoda indicate that
      laboratory protocol tests may give a reasonable prediction of short-term direct
      effects of chlorpyrifos for the same species inhabiting more complex aquatic
      systems.

PMID- 1379032
TI  - Clinical trial of FK 506 immunosuppression in adult cardiac transplantation.
AB  - The new immunosuppressive agent FK 506 was used as primary immunotherapy in
      conjunction with low-dose steroids and azathioprine in 72 patients subsequent to
      orthotopic cardiac transplantation. Overall patient survival at a mean follow-up
      of 360 days was 92%. The number of episodes of cardiac rejection (grade 3A or
      greater) within 90 days of transplantation was 0.95 per patient. The actuarial
      freedom from rejection at 90 days was 41%. Achievement of this level of
      immunosuppression is comparable with that of cyclosporine-based triple-drug
      therapy with OKT3 immunoprophylaxis. Thirty percent of patients were tapered off
      all steroids, and the average steroid dose in the group who received steroids was
      8.6 mg of prednisone per day. The incidence of infection reflected the diminished
      necessity for steroids: seven major infections (10%) and 11 minor infections
      (16%). Renal dysfunction occurred during the perioperative period in most
      patients in this trial. However, the incidence of hypertension was 54% compared
      with 70% during the cyclosporine era. Ten adults underwent successful rescue
      therapy with FK 506 after cardiac rejection refractory to conventional
      immunotherapy. Side effects of FK 506 were notably few, and the results of the
      trial are encouraging for the future of the cardiac transplant recipient.

PMID- 1379034
TI  - Palliative arterial repair for transposition, ventricular septal defect, and
      pulmonary vascular disease.
AB  - Failure to repair transposition of the great arteries and ventricular septal
      defect in the young infant results in the early development of pulmonary vascular
      occlusive disease. Complete repair, preferably by an arterial switch procedure
      and ventricular septal defect closure, may then not be possible. We report a
      palliative arterial switch procedure in a 5 1/2-year-old patient with
      transposition, ventricular septal defect, and severe pulmonary vascular
      obstructive disease in whom progressive hypoxemia and exercise intolerance
      developed. An arterial repair without ventricular septal defect closure was
      performed. After the operation, the child's systemic arterial oxygen saturation
      and exercise tolerance have substantially improved. Although the progression of
      pulmonary vascular disease may not be altered, arterial repair can provide
      effective palliation in this subset of patients.

PMID- 1379033
TI  - Univentricular atrioventricular connection with subaortic stenosis: a staged
      surgical approach.
AB  - A staged surgical approach was developed for the management of hearts with
      univentricular atrioventricular connection (double-inlet left ventricle or
      tricuspid atresia) and discordant ventriculoarterial connection with anatomical
      substrate for the development of subaortic stenosis. This consisted of initial
      palliation with pulmonary artery banding, followed by early elective relief of
      subaortic obstruction using a proximal pulmonary artery to ascending aorta
      anastomosis in infancy. Pulmonary blood flow was maintained at this time by
      creating a bidirectional superior cavopulmonary anastomosis. Over an 18-month
      period, 5 children, including 4 seen in the first week of life with aortic arch
      obstruction, were palliated with this approach. All patients survived operation
      and are asymptomatic with transcutaneous oxygen saturations of 80% to 85%.
      Completion of cavopulmonary repair is planned at 2 years of age. Although some
      authors have considered pulmonary artery banding contraindicated in these
      infants, the current staged approach offers an attractive alternative to the
      construction of a pulmonary artery to aorta anastomosis in the neonatal period.

PMID- 1379035
TI  - Cardiopulmonary bypass in the early puerperium: possible new role for aprotinin.
AB  - A case of successful emergency reoperation for mitral valve replacement 2 hours
      after a cesarean section is reported. The use of aprotinin (Trasylol; Bayer AG,
      Leverkusen, Germany) greatly simplified the surgical procedure and was in our
      opinion the most important factor in an uncomplicated outcome.

PMID- 1379036
TI  - Influence of age on the synthesis of macromolecules in the smooth muscle cells of
      the isolated myointimal mass in vitro.
AB  - The influence of growth and aging on the synthesis of DNA, RNA and protein in the
      myointima in vivo was explored by incubating isolated myointima of different ages
      in labelled precursors. As myointima grew and aged in vivo, the rates of DNA and
      protein synthesis declined, while the quantity of DNA increased more than two
      fold in seven days. The rate of RNA synthesis remained constant and was
      unaffected by growth. Like that of DNA and protein synthesis, fetal bovine serum
      was not required by the isolated myointima to synthesize RNA in vitro. Taken
      together, these findings confirm and extend our previous results which showed the
      synthetic autonomy of the isolated myointima, and demonstrate further that during
      growth the synthesis of RNA is affected in a manner that differs from that which
      controls DNA and protein.

PMID- 1379037
TI  - The chicken anterior lingual glands: structural study of carbohydrate chains by
      lectins and glycosidases.
AB  - Lectin histochemistry combined with glycosidase digestion was used to investigate
      the presence of glucidic residues and identify the terminal residues and their
      acceptor sugars in these glands. Quantitative evaluation of lectin-positive sites
      was made by histophotometrical scanning. Lectin histochemistry demonstrated that
      the anteromedial portion contains disaccharides sialic acid-D-Gal, sialic acid-D
      GalNAc and Fuc-D-Gal, and that the anterolateral portion contains the terminal
      dimer sialic acid-D-Gal only. These findings have hypothetical significance in
      terms of the known functions of chicken anterior lingual glands.

PMID- 1379038
TI  - Mapping of the epitope/paratope interactions of a monoclonal antibody directed
      against adenosine 3',5'-monophosphate.
AB  - A series of systematically modified cyclic AMP (cAMP) analogues, including newly
      synthesized benzimidazole ribofuranosyl 3',5'-monophosphates was used to map the
      essential molecular interactions between cAMP and the monoclonal antibody 4/2C2
      (mab 4/2C2) directed against 2'-O-succinoyl cAMP [Colling, Gilles, Nass, Moka &
      Jaenicke (1988) Second Messengers Phosphoproteins 12, 123-133]. Its paratope
      binds the purine base in syn conformation by dipole-dipole interactions and
      hydrophobic forces and/or stacking interactions. The ribose phosphate moiety is
      recognized by a combination of charge interactions and H-bonds to the exocyclic
      and the 5'-oxygen atoms and a hydrophobic interaction at the 2'-position. There
      is no regioselectivity for the exocyclic oxygen atoms. Compared with the known
      types of binding, mab 4/2C2 thus shows a new combination of molecular
      interactions which may be the basis of its strikingly specific recognition and
      binding of the cyclic adenylates. On this account mab 4/2C2 may become an
      important tool in studies on cAMP metabolism.

PMID- 1379039
TI  - Complementary DNA sequence of human amyloidogenic immunoglobulin light-chain
      precursors.
AB  - The primary structure of three amyloid precursor light chains was deduced from
      the sequence of complementary DNA (cDNA) from bone marrow cells from patients
      affected with classical lambda (patient Air) or kappa (patient Arn) amyloidosis
      and from a patient (Aub) in whom lambda amyloid deposits were unusual by their
      perimembranous location in the kidney glomerulus. All three RNAs were of normal
      size, as estimated by Northern blotting, and encoded normal-sized light chains.
      The deduced light-chain sequence from patient Arn was related to the V kappa 1
      subgroup, and included ten residues that had not been previously reported at
      these positions, only one of which (Leu-21) was located in a beta-sheet (4-2).
      The unusual presence of Asn-70 determined a potential N-glycosylation site. The
      sequence of the light chain from patient Air belonged to the V lambda 1 subgroup,
      and included three unusually located amino acid residues, one of which had
      already been reported in an amyloidogenic lambda-chain. The sequence of the light
      chain from patient Aub was related to the V lambda 3 subgroup, and contained five
      amino acid residues that had not previously been described at the corresponding
      positions; two of them (His-36 and Ser-77) were located in beta-sheets (3-1 and 4
      3 respectively). This sequence was also peculiar because of the presence of
      numerous acidic residues in the complementarity-determining regions. Such unusual
      primary structures might be responsible for the amyloidogenic properties of these
      light-chain precursors.

PMID- 1379040
TI  - Identification and characterization of a calmodulin-dependent nitric oxide
      synthase from GH3 pituitary cells.
AB  - A nitric oxide synthase activity stimulated more than 30-fold by the concurrent
      presence of Ca2+ and calmodulin (CaM), and inhibited by trifluoperazine (50
      microM), has been identified in extracts of GH3 pituitary cells. The CaM
      dependent nitric oxide synthase of the crude extract was stimulated more than 9
      fold by (6R)-5,6,7,8-tetrahydro-L-biopterin with half-maximal stimulation
      occurring at a concentration of 300 nM. Fractionation of the extract on DEAE
      cellulose enhanced nitric oxide synthase specific activity up to 300-fold and
      provided a preparation which on Western blot analysis possessed a 152 kDa protein
      which cross-reacted with antibodies to homogeneous bovine brain nitric oxide
      synthase. The DEAE-cellulose-purified enzyme exhibited apparent Km values of 4.3
      microM, 0.4 microM, 0.3 microM and 4 nM for L-arginine, NADPH, Ca2+ and CaM
      respectively. The CaM-dependent nitric oxide synthase of GH3 extract bound to
      2',5'-ADP-agarose and was eluted by NADPH with a 500-fold increased specific
      activity. Citrulline formation by the ADP-agarose-purified enzyme was inhibited
      by NG-nitro-L-arginine, NG-methyl-L-arginine and Nitro Blue Tetrazolium with
      apparent Ki values of 0.2, 1.8 and 7 microM respectively. The ADP-agarose
      purified enzyme displayed cytochrome c reductase activity which was stimulated
      more than 18-fold by the concurrent presence of Ca2+ and CaM and inhibited by
      trifluoperazine. NG-Nitro-L-arginine and NG-methyl-L-arginine did not inhibit the
      cytochrome c reductase activity.

PMID- 1379041
TI  - 'Pore' formation is not required for the hydroperoxide-induced Ca2+ release from
      rat liver mitochondria.
AB  - It has recently been suggested by several investigators that the hydroperoxide-
      and phosphate-induced Ca2+ release from mitochondria occurs through a non
      specific 'pore' formed in the mitochondrial inner membrane. The aim of the
      present study was to investigate whether 'pore' formation actually is required
      for Ca2+ release. We find that the t-butyl hydroperoxide (tbh)-induced release is
      not accompanied by stimulation of sucrose entry into, K+ release from, and
      swelling of mitochondria provided re-uptake of the released Ca2+ ('Ca2+ cycling')
      is prevented. We conclude that (i) the tbh-induced Ca2+ release from rat liver
      mitochondria does not require 'pore' formation in the mitochondrial inner
      membrane, (ii) this release occurs via a specific pathway from intact
      mitochondria, and (iii) a non-specific permeability transition ('pore' formation)
      is likely to be secondary to Ca2+ cycling by mitochondria.

PMID- 1379042
TI  - A DNA-dependent RNA synthesis by wheat-germ RNA polymerase II insensitive to the
      fungal toxin alpha-amanitin.
AB  - Wheat-germ RNA polymerase II is able to catalyse a DNA-dependent reaction of RNA
      synthesis in the presence of a high concentration (1 mg/ml) of the fungal toxin
      alpha-amanitin. This anomalous reaction is specifically directed by single
      stranded or double-stranded homopolymer templates, such as poly(dC) or
      poly(dC).poly(dG), and occurs in the presence of either Mn2+ or Mg2+ as the
      bivalent metal cofactor. In contrast, the transcription of other synthetic
      templates, such as poly(dT), poly(dA).poly(dT) or poly[d(A-T)] is completely
      abolished in the presence of 1 microgram of alpha-amanitin/ml, in agreement with
      well-established biochemical properties of class II RNA polymerases. Size
      analysis of reaction products resulting from transcription of (dC)n templates of
      defined lengths suggests that polymerization of RNA chains proceeds through a
      slippage mechanism. The fact that alpha-amanitin does not impede this synthetic
      reaction implies that the amatoxin interferes with the translocation of wheat
      germ RNA polymerase II along the DNA template.

PMID- 1379043
TI  - Eicosanoid-mediated contractility of hepatic stellate cells.
AB  - To approach experimentally the problem of contractility, stellate cells from rats
      were isolated and grown on a flexible silicone rubber substrate. Increases or
      decreases in the number of wrinkles of the silicone membrane beneath the cells
      that were easily observable by microscopy was employed as semi-quantitative
      measure of stellate cell motility. Contraction of stellate cells accompanied by
      diminution of cell body size was induced by U46619 (a thromboxane A2 analogue)
      and prostaglandin (PG) F2 alpha. Wrinkle formation became detectable 1.5 min
      after addition of 2 microM-U46619 and reached its maximum 10-15 min later. The
      effect of PGF2 alpha was not so striking, but lasted for a longer period of time.
      On the other hand, dibutyryl cyclic AMP, Iloprost (a PGI2 analogue) and PGE2 led
      to the disappearance or decrease in the number of wrinkles, indicating relaxation
      of contracted stellate cells. For instance, after addition of 2 microM-Iloprost,
      47, 75 and 82% of contracted stellate cells had relaxed within 5, 10 and 20 min
      respectively. Moreover, dibutyryl cyclic AMP induced disappearance of alpha
      smooth muscle actin stress fibres. This response became recognizable 10 min after
      addition of dibutyryl cyclic AMP; 40 min later, 97% of stellate cells were devoid
      of stress fibres. Thus stellate cells are able to undergo reversible contraction
      in primary culture, and the contraction of these cells may be mediated by
      eicosanoids that can be produced within the liver.

PMID- 1379044
TI  - Purification and characterization of an alpha-macroglobulin proteinase inhibitor
      from the mollusc Octopus vulgaris.
AB  - The cell-free haemolymph of the mollusc Octopus vulgaris inhibited the
      proteolytic activity of the thermolysin against the high-molecular-mass substrate
      hide powder azure. The purified inhibitor was a glycoprotein composed of two
      identical 180 kDa disulphide-linked subunits. In addition to the inhibition of
      the metalloproteinase thermolysin, the protein inhibited the serine proteinases
      human neutrophil elastase, pig pancreatic elastase, bovine chymotrypsin, bovine
      trypsin and the cysteine proteinase papain. A fraction of the proteinase
      inhibitor complex resisted dissociation after denaturation indicating that some
      of the proteinase molecules became covalently bound. The nucleophile beta
      aminopropionitrile decreased the covalent binding of proteinases to the Octopus
      vulgaris protein, suggesting that this interaction is mediated by an internal
      thiol ester; the reactivity and the amino acid sequence flanking the reactive
      residues of the putative thiol ester were consistent with this hypothesis. Bound
      trypsin remained active against the low-molecular-mass chromatogenic substrate H
      D-Pro-Phe-Arg p-nitroanilide and was protected from inhibition by active-site
      directed protein inhibitors of trypsin; however, the bound trypsin was readily
      inhibited by small synthetic inhibitors. This indicates that the inhibition of
      proteinases is accomplished by steric hindrance. The proteinase-inhibitory
      activity of this protein is characteristic of inhibition by mammalian alpha
      macroglobulins and the presence of a putative thiol ester suggests that the
      Octopus vulgaris proteinase inhibitor is a homologue of human alpha 2
      macroglobulin.

PMID- 1379045
TI  - Concurrent down-regulation of IP prostanoid receptors and the alpha-subunit of
      the stimulatory guanine-nucleotide-binding protein (Gs) during prolonged exposure
      of neuroblastoma x glioma cells to prostanoid agonists. Quantification and
      functional implications.
AB  - Neuroblastoma x glioma hybrid NG108-15 cells express a high-affinity IP
      prostanoid receptor. Saturation binding analysis of this receptor, using
      [3H]prostaglandin E1 ([3H]PGE1) as ligand, indicated that it was present at some
      1.5 pmol/mg of membrane protein and displayed a dissociation constant for this
      ligand of 30-40 nM. Prolonged exposure of these cells either to PGE1 or to
      iloprost, which is a stable analogue of prostacyclin, caused a 40-70% decrease in
      levels of the receptor. The remaining receptors were capable of interacting with
      the stimulatory G-protein (Gs) of the adenylate cyclase cascade, as saturation
      analysis of the binding of [3H]PGE1 indicated that they had a similar affinity
      for the 3H-labelled ligand, and because the specific binding of [3H]PGE1 to these
      receptors was still sensitive to the presence of poorly hydrolysed analogues of
      GTP. We have recently demonstrated that prolonged exposure of NG108-15 ells to
      PGE1 causes a cyclic AMP-independent loss of Gs alpha-subunit (Gs alpha) from
      these cells [McKenzie & Milligan (1990) J. Biol. Chem. 265, 17084-17093]. Steady
      state concentration of the larger 45 kDa form of Gs alpha (which is the
      predominant form expressed in these cells) was assessed to be 9.6 pmol/mg of
      membrane protein, and treatment with iloprost decreased levels of this
      polypeptide to some 3.0 pmol/mg of protein. Time courses of iloprost-mediated
      down-regulation of the IP prostanoid receptor, loss of Gs alpha protein as
      assessed by immunoblotting and loss of Gs alpha activity as assessed by the
      reconstitution of NaF stimulation of adenylate cyclase activity to membranes of
      S49 cyc- cells by sodium cholate extracts of NG108-15 cells were identical,
      suggesting that the loss of the IP prostanoid receptor and G-protein occurred in
      parallel. Each of these effects was half-maximal between 2 and 3 h of exposure to
      the agonist. Stoichiometry of loss of Gs alpha and IP prostanoid receptor was
      unchanged by the percentage receptor occupancy, and quantification indicated the
      loss of some 7-10 mol of Gs alpha/mol of receptor. This is the first report to
      demonstrate the temporal concurrence of loss of Gs alpha and of a receptor which
      interacts with this G-protein. Chronic activation of the IP prostanoid receptor
      on these cells results in the development of a heterologous form of
      desensitization to agents which function to activate adenylate cyclase [Kelly,
      Keen, Nobbs & MacDermot (1990) Br. J. Pharmacol. 99, 306-316]. Agonist regulation
      of Gs alpha levels in these cells may contribute to this process.

PMID- 1379046
TI  - Cloning and sequence analysis of a cDNA encoding the alpha-subunit of mouse beta
      N-acetylhexosaminidase and comparison with the human enzyme.
AB  - cDNAs encoding the mouse beta-N-acetylhexosaminidase alpha-subunit were isolated
      from a mouse testis library. The longest of these (1.7 kb) was sequenced and
      showed 83% similarity with the human alpha-subunit cDNA sequence. The 5' end of
      the coding sequence was obtained from a genomic DNA clone. Alignment of the human
      and mouse sequences showed that all three putative N-glycosylation sites are
      conserved, but that the mouse alpha-subunit has an additional site towards the C
      terminus. All eight cysteines in the human sequence are conserved in the mouse.
      There are an additional two cysteines in the mouse alpha-subunit signal peptide.
      All amino acids affected in Tay-Sachs-disease mutations are conserved in the
      mouse.

PMID- 1379047
TI  - Activation of protein kinase C is not an absolute requirement for amylase release
      from permeabilized rat pancreatic acini.
AB  - The effect of protein kinase C (PKC) on amylase discharge from streptolysin-O
      permeabilized rat pancreatic acini was investigated. Addition of phorbol 12
      myristate 13-acetate (PMA) to permeabilized cells potentiated Ca(2+)-stimulated
      release, but had no effect on discharge at non-stimulatory Ca2+ concentrations.
      PMA markedly shifted the Ca(2+)-concentration-dependence of amylase discharge to
      the left, by enhancing the time over which the permeabilized cells release. This
      effect was inhibited by both staurosporine and PKC-19-31-amide peptide inhibitor,
      indicating that the effect of PMA was due to its action on PKC. Staurosporine
      also partially inhibited amylase release at the optimal concentration of Ca2+;
      this effect was not replicated by the more specific PKC-19-31-amide peptide
      inhibitor and may be due to an effect on another second-messenger system. PKC
      appears to be an important modulator of release in pancreatic acini, but its
      activation is not an absolute requirement for Ca(2+)-dependent amylase discharge.

PMID- 1379049
TI  - Community education on stroke.
AB  - A programme of community education on stroke in Micronesia is based on the use of
      brightly illustrated posters with a limited content of written material in the
      native languages. This approach has been favourably received by the people.

PMID- 1379048
TI  - Purification and characterization of matrix metalloproteinase 9 from U937
      monocytic leukaemia and HT1080 fibrosarcoma cells.
AB  - The precursor of matrix metalloproteinase 9 (proMMP-9), also known as '92 kDa
      progelatinase/type IV procollagenase', was purified from the conditioned medium
      of U937 monocytic leukaemia and HT1080 fibrosarcoma cell lines stimulated with
      phorbol 12-myristate 13-acetate. ProMMP-9 in these culture media is non
      covalently complexed with the 29 kDa tissue inhibitor of metalloproteinases
      (TIMP), but free proMMP-9 was separated from the TIMP-proMMP-9 complex by
      chromatography on Green A Dyematrex gel. The final product was homogeneous on
      SDS/PAGE, with a molecular mass of 88 kDa without reduction and 92 kDa with
      reduction. Treatment of proMMP-9 with 4-aminophenylmercuric acetate converted the
      88 kDa precursor into 80 kDa and 68 kDa forms. Gelatin-containing zymographic
      analysis showed zones of lysis associated with all three species. However, only
      the 68 kDa species was shown to be catalytically active by its ability to bind to
      alpha 2-macroglobulin. In the presence of an equimolar amount of TIMP, only the
      80 kDa species was generated by treatment with 4-aminophenylmercuric acetate, but
      no enzyme activity was detected. This indicates that TIMP binds to the 80 kDa
      intermediate and inhibits the generation of the active 68 kDa species. Eight
      endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin,
      cathepsin G, neutrophil elastase and thermolysin) were tested for their ability
      to activate proMMP-9. Of them, trypsin was the most effective activator of proMMP
      9. Only partial activation (10-30%) was observed with plasmin, cathepsin G and
      chymotrypsin. The active forms generated by trypsin were identified as 80 kDa, 74
      kDa and 66 kDa by their abilities to bind to alpha 2-macroglobulin. In the
      presence of an equimolar amount of TIMP, proMMP-9 was also converted into the
      same molecular-mass species by trypsin, but they were not proteolytically active.
      This suggests activated MMP-9 is inhibited by TIMP. Activated MMP-9 digested
      gelatin, type-V collagen, reduced carboxymethylated transferrin and, to a lesser
      extent, type-IV collagen and laminin A chain. The specific activity against
      gelatin was estimated to be 15,000 units/mg (1 unit = 1 microgram of gelatin
      degraded/min at 37 degrees C) by titration with alpha 2-macroglobulin.
      Comparative studies on digestion of gelatin and collagen types IV and V by MMP-9
      and MMP-2 indicated that both enzymes degrade these substrates into similar
      fragments. However, the susceptibilities of laminin, fibronectin and reduced
      carboxymethylated transferrin to these two MMPs were sufficiently different to
      indicate differences in substrate specificities between these two closely related
      proteinases.

PMID- 1379050
TI  - Cardiac inotropic effects of ethanol and calcium-channel modulators.
AB  - Our objective was to analyze the influence of ethanol ingestion on the in vitro
      inotropic effects of dihydropyridines alone, or in combination with ethanol, on
      atrial muscle from rats offered a liquid diet with ethanol ("ethanol rats," ER)
      or without ethanol ("normal rats," NR). Left atria from NR or ER were superfused
      with Tyrode's solution (36 degrees C) and driven at 1.5 Hz while recording
      tension. Bay K 8644 (BAYK) increased, while nimodipine or ethanol decreased, the
      tension developed and the velocity of development of tension. The preparations
      recovered rapidly from the effects of ethanol, but not from those of the
      dihydropyridines. The effects of ethanol and dihydropyridines in combination were
      the result of the additive or counteractive actions of the drugs. The effects of
      ethanol and nimodipine on ER preparations were not different from those observed
      in NR. The action of BAYK was significantly smaller in ER than in NR. In other
      words, chronic ingestion of ethanol reduced the positive inotropic effect of
      BAYK, but it did not modify the negative inotropic action of nimodipine or
      ethanol.

PMID- 1379051
TI  - Renal effects of the nitric oxide synthase inhibitor, L-NG-nitroarginine, in
      dogs.
AB  - L-NG-Nitroarginine (LNNA), an analog of L-arginine, was infused into the renal
      artery of anesthetized dogs to assess the contribution of nitric oxide production
      in the regulation of renal hemodynamics and urine formation. Following intrarenal
      arterial infusion of LNNA (15 micrograms/kg/min) for 25 min, renal blood flow
      (RBF) gradually decreased and there was no reversion even 60 min after cessation
      of infusion, with no change in mean arterial blood pressure (MBP) and heart rate.
      Urine flow (UF) decreased while the glomerular filtration rate (GFR) did not
      change. The highest dose of LNNA (75 micrograms/kg/min) remarkably decreased RBF
      and increased MBP. The renal vasocontriction and pressor responses induced by the
      highest dose of LNNA were significantly antagonized by an intravenous
      administration of L-arginine (100 mg/kg/min). LNNA is characterized as a potent
      and long-lasting renal vasoconstrictor and decreases GFR, UF, and sodium
      excretion. It is suggested that nitric oxide produced in the kidney may have a
      significant role in the regulation of basal renal circulation and exert diuresis
      and natriuresis.

PMID- 1379052
TI  - Immunoassay principle based on exchange reactions: investigations on agarose gel
      and silanized quartz.
AB  - Preliminary studies of a new immunoassay principle based on exchange reactions is
      reported. Exchange of 125I-labelled insulin with unlabelled insulin from
      immobilized monoclonal antibodies was investigated. From antibody immobilized on
      a gel substrate the tagged insulin was exchanged according to a first-order
      process. With antibody immobilized on a quartz substrate by two different
      methods, the kinetics was changed dramatically, probably because of the non
      specific interaction between the ligand and the surface. The recorded adsorption
      isotherms could not be described by the Langmuir adsorption equation, and a model
      allowing for non-specific adsorption of the ligand was developed. This model gave
      a satisfactory fit to the experimental data, allowing computation of adsorption
      parameters. It is concluded that even the best method used to immobilize
      receptors on quartz is not adequate for an exchange assay to be made. However,
      this coating method may lead to more sensitive receptor-based assays of more
      conventional type.

PMID- 1379053
TI  - Effects of endothelial cell growth factor on vascular compromised skin flaps.
AB  - Angiogenic growth factors have the potential to accelerate vascularization in
      soft tissue. This study explored the vascular effects of endothelial cell growth
      factor (1800 micrograms/mL) with heparin (7 micrograms/mL) in gelatin sponge
      (Gelfoam) in two settings of vascular compromise. On days 2 and 3 ligated skin
      flaps in the rabbit ear model, peripheral neovascularization, and flap viability
      were quantitatively documented by digital angiographic analysis and by polar
      planimetry. The mean flap viability of the treated flaps was two times greater
      than their controls in the day 2 (N = 24) and day 3 ligation groups (N = 22). The
      angiograms among the treated flaps in the day 2 ligation group also demonstrated
      a quantitative increase in vascularization compared with their controls. These
      results suggest a provocative means for accelerating neovascularization and
      enhancing viability to vascular compromised skin flaps.

PMID- 1379054
TI  - Inhibitory effect of loratadine and clemastine on histamine release in human
      skin.
AB  - The inhibitory effect of the two H1 antagonists clemastine and loratadine on
      histamine release in human skin was studied in 15 volunteers. The antihistamines
      and placebo were administered orally (clemastine 2 mg twice a day, loratadine 10
      mg once a day) for 5 days according to a double-blind, crossover design.
      Clemastine caused a significant sedation in comparison with placebo, whereas
      there was no difference between loratadine and placebo in this respect. After 5
      days' medication, flare reaction was induced by intradermal injection of
      histamine and the histamine liberator compound 48/80. The antihistamine dosages
      were approximately equipotent and inhibited the flare response induced by
      histamine to about the same extent, whereas the flares induced by compound 48/80
      were still more inhibited by both drugs. The results indicate that clemastine and
      loratadine not only inhibit histamine effects at H1 receptor level, but have
      additional suppressive effects, probably due to inhibition of mast cell
      degranulation. The simple, virtually noninvasive, in vivo technique described in
      this paper does not require chemical analysis of the released mediators and could
      be used to screen 'mast cell stabilizing' effects of various antihistamines.

PMID- 1379055
TI  - Atracurium and histamine.

PMID- 1379056
TI  - Colloid (3% Dextran 70) with or without ephedrine infusion for cardiovascular
      stability during extradural caesarean section.
AB  - Using a non-invasive cardiac output monitor (Bo-Med NCCOM 3-R7), we have compared
      cardiovascular responses, degree of haemodilution and incidence of nausea during
      extradural Caesarean section in healthy non-labouring mothers given either
      ephedrine 17.5 mg and 3% Dextran 70 7.5 ml kg-1 before delivery (group A) or
      volume loading with Dextran 15 ml kg-1 without infusion of ephedrine (group B).
      Smallest systolic arterial pressures before delivery were 114 (SEM 4) mm Hg
      (group A) and 105 (5) (group B). There were no significant differences between
      the groups in mean arterial pressure, heart rate, systemic vascular resistance or
      central venous pressure, while cardiac output increased more with the ephedrine
      infusion (P less than 0.05). Haemodilution was 8% in group A and 16% in group B
      at the time of delivery. Ephedrine infusion was associated with a smaller
      incidence of nausea (P less than 0.01). Umbilical arterial pH values were not
      different between the two groups. We conclude that infusion of ephedrine,
      combined with low volume colloid administration, is a safe alternative to more
      extensive colloid volume expansion for control of hypotension and provides
      effective prophylaxis against nausea during extradural Caesarean section in
      healthy non-labouring mothers.

PMID- 1379057
TI  - Comparison of four serum tumour markers in the diagnosis of colorectal carcinoma.
AB  - The assessment of the diagnostic power of four serum tumour markers, CEA, CA 19
      9, CA 50 and CA 195 for colorectal carcinoma is described, according to recently
      formulated guidelines. Preoperative serum concentrations of the four markers were
      determined in 198 colorectal cancer patients and 57 patients with a benign
      colorectal disorder. The cumulative frequency distributions of the malignant and
      benign group show strong overlap for all markers, which indicates low diagnostic
      ability. This is confirmed by the Receiver Operating Characteristic curves, which
      have areas under the curve of 0.65 (95% confidence interval (CI) 0.58-0.73) for
      CA 19-9, CA 50 and CA 195 and of 0.70 (95%) CI 0.63-0.77) for CEA. The new tumour
      markers appear to be of slightly less diagnostic value than CEA for the primary
      diagnosis of colorectal cancer, although the discrepancy is not statistically
      significant. The low diagnostic power of CA 19-9, CA 50 and CA 195 may be due to
      a high proportion of colorectal cancer patients having the Lewis(a-b-) phenotype,
      who cannot synthesise these markers.

PMID- 1379058
TI  - 89Strontium in bone metastases from hormone resistant prostate cancer: palliation
      effect and biochemical changes.
AB  - Hematological and biochemical parameters were evaluated in 31 patients receiving
      150 MBq 89Strontium (89Sr) intravenously due to painful skeletal metastases from
      hormone resistant prostate cancer. Two and 3 months after the injection prostate
      specific antigen (PSA) had increased by a median of 36% and 100%, respectively,
      as compared to the pretreatment value whereas alkaline phosphatase (APHOS) had
      decreased by about 20% (median). The leucocyte and platelet counts were reduced
      by about 20-35%, without reaching grade greater than or equal to 2 toxicity. Pain
      relief was reported in 14 of 29 evaluable patients at 2 months and in 11 of 23
      patients at 3 months. It is concluded that 89Sr represents a worthwhile
      therapeutic modality in the palliation treatment of patients with hormone
      resistant prostate cancer, though the biological significance of frequently
      increasing PSA and decreasing APHOS is not yet completely understood.

PMID- 1379059
TI  - The prognostic significance of prostate specific antigen in metastatic hormone
      resistant prostate cancer.
AB  - Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate
      cancer had normal serum levels of prostate specific antigen (PSA less than or
      equal to 10 micrograms l-1), when referred for secondary treatment. PSA was
      significantly correlated with the extent of skeletal metastases (R: 0.35) and the
      levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a
      multivariate Cox regression analysis the survival of the 152 patients was not
      correlated with the PSA level but with the patients performance status, the level
      of hemoglobin, and the time between primary hormone treatment and relapse. The
      lack of serum PSA to predict survival may be explained by a heterogenous
      composition of hormone resistant prostate cancer as regards differentiated and/or
      PSA producing vs undifferentiated and/or PSA non-producing cells.

PMID- 1379061
TI  - Expression of a growth arrest specific gene (gas-1) in transformed cells.
AB  - A set of growth arrest-specific (gas) genes negatively regulated by serum has
      been identified. We report the analysis of the expression of one of them (gas-1)
      in transformed cells. We found a down regulation of gas-1 expression in NIH 3T3
      cells transfected in vitro with an activated Ha-ras oncogene. In five chemically
      induced mouse tumours grown in vivo the amounts of gas-1 mRNA were largely
      different but not related to the proliferating activity (evaluated by both H3
      histone expression and 3H-thymidine incorporation into DNA). The amount of gas-1
      mRNA in the tumours was in general higher than in normal tissues. Expression of c
      myc was also evaluated and found to be high in tumours which exhibited low gas-1
      expression. Two fibrosarcomas, CA-2 and CB-20, with similar phenotype, similar
      growth rate, different expression of c-myc and 100-fold difference in gas-1
      expression were further investigated and gas-1 expression was found to be
      correlated with the expression of a differentiated function (as judged from
      collagen expression). Cell lines derived from CA-2 and CB-20 and maintained under
      different culture conditions showed that the cell cycle regulation and serum
      response of gas-1 expression were lost in CA-2. The higher steady state level of
      gas-1 mRNA in spite of a shorter mRNA half life suggests that in CB-20 cells the
      gas-1 gene is transcribed faster than in CA-2 cells indicating that
      transcriptional regulation is the major determinant of gas-1 gene expression in
      tumour cells. The finding of gas-1 expression in tumour cells suggests that its
      expression is not sufficient to maintain cells into quiescence, however, as a
      marker specific for the G0 phase, it could be useful, in conjunction with other
      growth related genes, to define the cell cycle distribution of a cell population.

PMID- 1379060
TI  - Changes in serotonin metabolism in cancer patients: its relationship to nausea
      and vomiting induced by chemotherapeutic drugs.
AB  - The metabolism of serotonin was studied in cancer patients of their first day of
      their first course of chemotherapeutic drugs either with strongly or moderately
      emetogenic regimens. It was observed that strongly emetogenic treatments induce
      greater increases in serotonin release than moderately emetogenic regimens. High
      dose cisplatinum (75 +/- 5 or 83.8 +/- 5 mg m-2) produced a marked increase in
      the plasma levels and in the urinary excretion of 5-hydroxyindole acetic acid (5
      HIAA). Neither platelet nor plasma (platelet-free plasma) serotonin were
      significantly modified by high-dose cisplatinum. Dacarbazine (283 +/- 22 mg m-2),
      another strongly emetogenic agent, induced acute nausea and emesis paralleled by
      marked increases in the urinary excretion of 5-HIAA. Both for high-dose
      cisplatinum and dacarbazine, the increases in serotonin metabolism occurred with
      a similar time-course than those of vomiting, and lasted for a period of 4 to 8
      h. Low-dose cisplatinum (30.8 +/- 3 mg m-2) as well as cyclophosphamide-based
      chemotherapies (520 +/- 30 mg m-2) produced very small increases in the urinary
      excretion of 5-HIAA. Platelet and plasma serotonin levels failed to increase in
      cyclophosphamide-treated patients. Octreotide, a long-acting somatostatin analog,
      did not inhibit the increase in urinary 5-HIAA and the nausea and vomiting
      produced by high-dose cisplatinum. These results suggest that for treatments that
      induce marked increases in serotonin release such as high-dose cisplatinum or
      dacarbazine: (a) the amount and time course of serotonin release induced by
      chemotherapeutic drugs determines the severity, time of onset and pattern of
      emesis observed; (b) platelet serotonin play no role in chemotherapy-induced
      emesis; (c) strongly emetogenic regimens release serotonin from enterochromaffin
      cells; and (d) intestinal release of serotonin is the consequence of the damage
      induced by the chemotherapeutic drugs on the gut mucosa.

PMID- 1379064
TI  - Paraneoplastic follicular hyperkeratosis responsive to etretinate.

PMID- 1379063
TI  - Distribution of complement regulators (CD46, CD55 and CD59) in skin appendages,
      and in benign and malignant skin neoplasms.
AB  - Immunohistochemical studies were performed to establish the distribution of
      membrane cofactor protein (MCP; CD46), decay-accelerating (DAF; CD55) and
      homologous restriction factor (HRF20; CD59), in normal skin appendages, and in
      benign and malignant skin neoplasms. At least two of these regulators were
      detected on normal eccrine glands, apocrine glands and sebaceous glands. They
      were also found in cellular naevi (CN), seborrhoeic keratoses (SK), basal cell
      carcinoma (BCC), Bowen's disease (BD), squamous cell carcinoma (SCC) and Paget's
      disease (PD). Although there were slight differences in their distribution, these
      regulators were found in all the cells examined, indicating that they are
      essential factors in human skin as well as other organs, and in neoplasms, in
      preventing autologous complement attack.

PMID- 1379062
TI  - Specific detection of c-erbB-2 mRNA expression in gastric cancers by the
      polymerase chain reaction following reverse transcription.
AB  - The expression of the c-erbB-2 mRNA in human embryonic lung fibroblasts, a
      gastric cancer cell line, mature placenta, and 25 gastric cancer tissues was
      examined by using the polymerase chain reaction following reverse transcription.
      This technique can be used to examine c-erbB-2 mRNA expression in a small
      endoscopic biopsy specimen before surgery.

PMID- 1379065
TI  - Detection of hydatidiform mole in maternal serum screening programmes for Down's
      syndrome.
AB  - OBJECTIVE: To determine how frequently hydatidiform mole will be detected in a
      maternal serum Down's syndrome screening programme. DESIGN: Affected pregnancies
      were identified using a national register. Unconjugated oestriol (uE3) and human
      chorionic gonadotrophin (hCG) were measured in stored serum samples and
      alphafetoprotein (AFP) levels were available from previous neural tube defect
      screening at 15-20 weeks gestation. SUBJECTS: Ten pregnancies with a complete
      mole (i.e., hydropic placenta without a fetus), nine with stored serum samples
      and one with an AFP level only. RESULTS: The median values were 0.08, 0.13 and
      1.83 multiples of the normal median for AFP, uE3 and hCG respectively. Six out of
      nine (67%) tested for all three markers had a high risk of Down's syndrome given
      maternal age and the marker levels. CONCLUSION: Many molar pregnancies that have
      not presented clinically before 15 weeks will be detected through Down's syndrome
      screening.

PMID- 1379066
TI  - Maternal serum alpha-fetoprotein levels in pregnant women with gestational
      diabetes.

PMID- 1379067
TI  - Early amniocentesis: alphafetoprotein levels in amniotic fluid, extraembryonic
      coelomic fluid and maternal serum between 8 and 13 weeks.

PMID- 1379068
TI  - Nitric oxide synthase is a cytochrome P-450 type hemoprotein.
AB  - Nitric oxide has emerged as an important mammalian metabolic intermediate
      involved in critical physiological functions such as vasodilation, neuronal
      transmission, and cytostasis. Nitric oxide synthase (NOS) catalyzes the five
      electron oxidation of L-arginine to citrulline and nitric oxide. Cosubstrates for
      the reaction include molecular oxygen and NADPH. In addition, there is a
      requirement for tetrahydrobiopterin. NOS also contains the coenzymes FAD and FMN
      and demonstrates significant amino acid sequence homology to NADPH-cytochrome P
      450 reductase. Herein we report the identification of the inducible macrophage
      NOS as a cytochrome P-450 type hemoprotein. The pyridine hemochrome assay showed
      that the NOS contained a bound protoporphyrin IX heme. The reduced carbon
      monoxide binding spectrum shows an absorption maximum at 447 nm indicative of a
      cytochrome P-450 hemoprotein. A mixture of carbon monoxide and oxygen (80%/20%)
      potently inhibited the reaction (73-79%), showing that the heme functions
      directly in the oxidative conversion of L-arginine to nitric oxide and
      citrulline. Additionally, partially purified NOS from rat cerebellum was
      inhibited by CO, suggesting that this isoform may also contain a P-450-type heme.
      NOS is the first example of a soluble cytochrome P-450 in eukaryotes. In
      addition, the presence of FAD and FMN indicates that this is the first
      catalytically self-sufficient mammalian P-450 enzyme, containing both a reductase
      and a heme domain on the same polypeptide.

PMID- 1379069
TI  - Mechanism of iberiotoxin block of the large-conductance calcium-activated
      potassium channel from bovine aortic smooth muscle.
AB  - The interaction of iberiotoxin (IbTX) with the large-conductance calcium
      activated potassium (maxi-K) channel was examined by measuring single-channel
      currents from maxi-K channels incorporated into planar lipid bilayers. Addition
      of nanomolar concentrations of IbTX to the external side of the channel produced
      long nonconducting silent periods, which were interrupted by periods of normal
      channel activity. The distributions of durations of blocked and unblocked periods
      were both described by single exponentials. The mean duration of the unblocked
      periods decreased in proportion with the external concentration of IbTX, while
      the mean duration of the blocked periods was not affected. These results suggest
      that IbTX blocks the maxi-K channel through a simple bimolecular binding reaction
      where the silent periods represent times when a single toxin molecule is bound to
      the channel. In symmetric solutions of 150 mM KCl, with a membrane potential of
      40 mV, the mean duration of the blocked periods produced by IbTX was 840 s, and
      the association rate was 1.3 x 10(6) M-1 s-1, yielding an equilibrium
      dissociation constant of about 1 nM. Raising the internal potassium concentration
      increased the dissociation rate constant of IbTX in a manner which was well
      described by a saturable binding function for potassium. External
      tetraethylammonium ion increased the average duration of the unblocked periods
      without affecting the blocked periods, suggesting that tetraethylammonium and
      IbTX compete for the same site near the conductance pathway of the channel.
      Increasing the external concentration of monovalent cations from 25 to 300 mM
      with either potassium or sodium decreased the rate of binding of IbTX to the
      channel by approximately 24-fold, with little effect on the rate of toxin
      dissociation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379070
TI  - Activation of DNA cleavage by dynemicin A in a B-Z conformational junction.
AB  - We report here that the DNA strand scission by dynemicin A is not only sequence
      specific but also conformation-specific. The salt-induced B----Z conformational
      transition dramatically enhanced the cleavage by dynemicin A in a B-Z junction
      region. By contrast, the bleomycin-Fe(II) complex, the elsamicin A-Fe(II)
      complex, and esperamicin A1 did not induce any preferential DNA cutting in such a
      DNA structure. The characteristic hyperreactivity of dynemicin A is observed in
      (dC-dG)8- and (dC-dG)12-inserted DNAs, but not in (dC-dG)5-inserted DNA. These
      results suggest value in the use of dynemicin A as proof of the existence of a B
      Z junction in vivo and also may aid in understanding the structure of B-Z
      junctions.

PMID- 1379071
TI  - Mechanistic probes of N-hydroxylation of L-arginine by the inducible nitric oxide
      synthase from murine macrophages.
AB  - NG-Hydroxy-L-arginine, [15N]-NG-hydroxy-L-arginine, and NG-hydroxy-NG- methyl-L
      arginine were used as mechanistic probes of the initial step in the reaction
      catalyzed by nitric oxide synthase isolated from murine macrophages. NG-Hydroxy-L
      arginine was found to be a substrate for nitric oxide synthase with a Km equal to
      28.0 microM, yielding nitric oxide and L-citrulline. NADPH was required for the
      reaction and (6R)-tetrahydro-L-biopterin enhanced the initial rate of nitric
      oxide formation. The stoichiometry of NG-hydroxy-L-arginine loss to L-citrulline
      and nitric oxide (measured as nitrite and nitrate) formation was found to be
      1:1:1. NG-Hydroxy-L-arginine was also observed in small amounts from L-arginine
      during the enzyme reaction. Studies with [15N]-NG-hydroxy-L-arginine indicated
      that the nitrogen in nitric oxide is derived from the oxime nitrogen of [15N]-NG
      hydroxy-L- arginine. NG-Hydroxy-NG-methyl-L-arginine was found to be both a
      reversible and an irreversible inhibitor of nitric oxide synthase, displaying
      reversible competitive inhibition with K(i) equal to 33.5 microM. As an
      irreversible inhibitor, NG-hydroxy-NG-methyl-L-arginine gave kinact equal to 0.16
      min-1 and KI equal to 26.5 microM. This inhibition was found to be both time- and
      concentration-dependent as well as showing substrate protection against
      inactivation. Gel filtration of an NG-hydroxy-NG-methyl-L-arginine-inactivated
      nitric oxide synthase failed to recover substantial amounts of enzyme activity.

PMID- 1379072
TI  - Induced peptide conformations in different antibody complexes: molecular modeling
      of the three-dimensional structure of peptide-antibody complexes using NMR
      derived distance restraints.
AB  - Intramolecular interactions in bound cholera toxin peptide (CTP3) in three
      antibody complexes were studied by two-dimensional transferred NOE spectroscopy.
      These measurements together with previously recorded spectra that show
      intermolecular interactions in these complexes were used to obtain restraints on
      interproton distances in two of these complexes (TE32 and TE33). The NMR-derived
      distance restraints were used to dock the peptide into calculated models for the
      three-dimensional structure of the antibody combining site. It was found that
      TE32 and TE33 recognize a loop comprising the sequence VPGSQHID and a beta-turn
      formed by the sequence VPGS. The third antibody, TE34, recognizes a different
      epitope within the same peptide and a beta-turn formed by the sequence IDSQ.
      Neither of these two turns was observed in the free peptide. The formation of a
      beta-turn in the bound peptide gives a compact conformation that maximizes the
      contact with the antibody and that has greater conformational freedom than alpha
      helix or beta-sheet secondary structure. A total of 15 antibody residues are
      involved in peptide contacts in the TE33 complex, and 73% of the contact area in
      the antibody combining site consists of the side chains of aromatic amino acids.
      A comparison of the NMR-derived models for CTP3 interacting with TE32 and TE33
      with the previously derived model for TE34 reveals a relationship between amino
      acid sequence and combining site structure and function. (a) The three aromatic
      residues that interact with the peptide in TE32 and TE33 complexes, Tyr 32L, Tyr
      32H, and Trp 50H, are invariant in all light chains sharing at least 65% identity
      with TE33 and TE32 and in all heavy chains sharing at least 75% identity with
      TE33. Although TE34 differs from TE32 and TE33 in its fine specificity, these
      aromatic residues are conserved in TE34 and interact with its antigen. Therefore,
      we conclude that the role of these three aromatic residues is to participate in
      nonspecific hydrophobic interactions with the antigen. (b) Residues 31, 31c, and
      31e of CDR1 of the light chain interact with the antigen in all three antibodies
      that we have studied. The amino acids in these positions in TE34 differ from
      those in TE32 and TE33, and they are involved in specific polar interactions with
      the antigen. (c) CDR3 of the heavy chain varies considerably both in length and
      in sequence between TE34 and the two other anti-CTP3 antibodies. These changes
      modify the shape of the combining site and the hydrophobic and polar interactions
      of CDR3 with the peptide antigen.

PMID- 1379073
TI  - Lipid modulation of nicotinic acetylcholine receptor function: the role of
      neutral and negatively charged lipids.
AB  - The effects of negatively charged and neutral lipids on the function of the
      reconstituted nicotinic acetylcholine receptor from Torpedo californica were
      determined with two assays using acetylcholine receptor-containing vesicles: the
      ion flux response and the affinity-state transition. The receptor was
      reconstituted into three different lipid environments, with and without neutral
      lipids: (1) phosphatidylcholine/phosphatidylserine; (2)
      phosphatidylcholine/phosphatidic acid; and (3) phosphatidylcholine/cardiolipin.
      Analysis of the ion flux responses showed that: (1) all three negatively charged
      lipid environments gave fully functional acetylcholine receptor ion channels,
      provided neutral lipids were added; (2) in each lipid environment, the neutral
      lipids tested were functionally equivalent to cholesterol; and (3) the rate of
      receptor desensitization depends upon the type of neutral lipid and negatively
      charged phospholipid reconstituted with the receptor. The functional effects of
      neutral and negatively charged lipids on the acetylcholine receptor are discussed
      in terms of protein-lipid interactions and stabilization of protein structure by
      lipids.

PMID- 1379074
TI  - Structural dynamics of translating ribosomes.
AB  - We describe three groups of small angle neutron scattering (SANS) experiments
      with translating ribosomes: 1) regular protonated (normal abundance hydrogen)
      particles; 2) two isotopic hybrid particles which are reconstituted from one
      protonated and the other deuterated subunit; 3) four isotypic hybrid particles
      differing from each other by the extent of protein and RNA deuteration. Using the
      SANS contrast variation method the radii of gyration of protein and RNA
      components in both ribosomal subunits as well as the intersubunit distance in the
      pre- and post-translocation states were determined. The results obtained suggest
      the following model of the ribosome as a dynamic machine. The ribosome oscillates
      between two major conformers differing in geometrical dimensions. The 'active'
      (pulsating) part of the ribosome is the 30S subunit. We believe that the movement
      of its 'head' relative to the passive 50S subunit is the main mechanical act of
      translocation. The radius of gyration of the 30S subunit and the intersubunit
      distance change upon the movement. This is corroborated by neutron scattering
      data.

PMID- 1379075
TI  - Mapping the three-dimensional locations of ribosomal RNA and proteins.
AB  - Seven regions of 16S rRNA have been located on the surface of the 30S ribosomal
      subunit by DNA hybridization electron microscopy in our laboratory. In addition,
      we have recently mapped the three-dimensional locations of an additional seven
      small ribosomal proteins by immunoelectron microscopy. The information from the
      direct mapping of the sites on rRNA has been incorporated into a model for the
      tertiary structure of 16S rRNA, accounting for approximately 40% of the total 16S
      rRNA. A novel structure, the platform ring, is proposed for a region of rRNA
      within the central domain. This structure rings the edges of the platform and
      includes regions 655-751 and 769-810. Another region, the recognition complex,
      consists of nucleotides 500-545, and occupies a region on the exterior surface of
      the subunit, near the EF-Tu binding site. In addition, 19 of the 21 small subunit
      ribosomal proteins have been mapped by immunoelectron microscopy in our
      laboratory. In order to evaluate the reliability of our model for the three
      dimensional distribution of 16S rRNA, we have predicted which sites of rRNA are
      adjacent to ribosomal proteins and compared these predictions with r-protein
      protection studies of others. Good correlation between the model, the locations
      of rRNA sites, the locations of ribosomal proteins, and regions of rRNA protected
      by ribosomal proteins, provides independent support for this model.

PMID- 1379076
TI  - Structure-function correlations (and discrepancies) in the 16S ribosomal RNA from
      Escherichia coli.
AB  - The published model for the three-dimensional arrangement of E coli 16S RNA is re
      examined in the light of new experimental information, in particular cross
      linking data with functional ligands and cross-links between the 16S and 23S RNA
      molecules. A growing body of evidence suggests that helix 18 (residues 500-545),
      helix 34 (residues 1046-1067/1189-1211) and helix 44 (residues 1409-1491) are
      incorrectly located in the model. It now appears that the functional sites in
      helices 18 and 34 may be close to the decoding site of the 30S subunit, rather
      than being on the opposite side of the 'head' of the subunit, as hitherto
      supposed. Helix 44 is now clearly located at the interface between the 30S and
      50S subunits. Furthermore, almost all of the modified bases in both 16S and 23S
      RNA appear to form a tight cluster near to the upper end of this helix,
      surrounding the decoding site.

PMID- 1379077
TI  - Comparison of dissimilarity patterns of E coli, yeast and mammalian tRNAs.
AB  - A number of experimental approaches have been developed for identification of
      recognition (identity) sites in tRNAs. Along with them a theoretical methodology
      has been proposed by McClain et al that is based on concomitant analysis of all
      tRNA sequences from a given species. This approach allows an evaluation of
      nucleotide combinations present in isoacceptor tRNAs specific for the given amino
      acid, and not present in equivalent positions in cloverleaf structure in other
      tRNAs of the same organism. These elements predicted from computer analysis of
      the databank could be tested experimentally for their participation in forming
      recognition sites. The correlation between theoretical predictions and
      experimental data appeared promising. The aim of the present work consisted of
      introducing further improvements into McClain's procedure by: i), introducing
      into analysis a variable region in tRNAs which had not been previously
      considered; to accomplish this, 'normalization' of variable nucleotides was
      suggested, based on primary and tertiary structures of tRNAs; ii), developing a
      new procedure for comparison of patterns for synonymous and non-synonymous tRNAs
      from different organisms; iii), analysis of 3- and 4-positional contacts between
      tRNAs and enzymes in addition to a formerly used 2-positional model. A systematic
      application of McClain's procedure to mammalian, yeast and E coli tRNAs led to
      the following results: i), imitancy patterns for non-synonymous tRNAs of any
      amino acid specificity and from any organisms analysed so far overlap by no more
      than 30%, providing a structural basis for discrimination with high fidelity
      between cognate and non-cognate tRNAs; ii), the predicted identity sites are non
      randomly distributed within tRNA molecules; the dominant role is ascribed to only
      two regions--anticodon and amino acid stem which are located far apart from one
      another at extremes of all tRNA molecules; iii), the imitancy patterns for
      synonymous tRNAs in lower (yeast) and higher (mammalian) eukaryotes are similar
      but not identical; iv), distribution of predicted identity sites in the
      cloverleaf structure in prokaryotes and eukaryotes is essentially different: in
      eubacterial tRNAs the major role in recognition plays anticodon and/or amino acid
      acceptor stem, whereas in eukaryotic (both unicellular and multicellular) tRNAs
      the remaining part of the molecules is also involved in recognition; v), the
      imitancy patterns of synonymous tRNAs from prokaryotes and eukaryotes are
      dissimilar, this observation leads to the prediction that the tRNA identity sites
      for the same amino acid in prokaryotes and eukaryotes may differ.

PMID- 1379078
TI  - Determination of tRNA(Phe) recognition nucleotides for phenylalanyl-tRNA
      synthetase from Thermus thermophilus.
AB  - The tRNA(Phe) recognition nucleotides for phenylalanyl-tRNA synthetase from an
      extreme thermophile Thermus thermophilus were investigated. Using yeast tRNA(Phe)
      T7 transcripts with various point mutations it was shown that four recognition
      points (G34, A35, A36 from anticodon and A73 from acceptor stem) are important
      for aminoacylation at 37 degrees C. In the case of the 73rd discriminator base A-
      --U, but not A----C, substitution suppresses aminoacylation. Position 20, which
      proved to be essential for all phenylalanyl-tRNA synthetases so far studied, is
      not involved in the recognition of tRNA(Phe) by the T thermophilus enzyme.

PMID- 1379079
TI  - Identification of the Escherichia coli 30S ribosomal subunit protein neighboring
      mRNA during initiation of translation.
AB  - To identify the proteins of the 30S ribosomal subunit of E coli that neighbor
      mRNA in the ternary initiation complex (mRNA*30S subunit*tRNA(fMet), we used an
      affinity cross-linking approach in which photoactivated groups were attached to
      different positions along the mRNA chain. A series of mini-genes originating from
      the 5'-end region of the cro gene of lambda bacteriophage were constructed as
      templates for mini-mRNA synthesis. Two strategies were used to introduce photo
      reactive agents into the message. According to the first, two transcripts were
      isolated from E coli and chemically derivatized at their 5'-ends with a
      photoinducible diaziril group. One of these messages allowed for localization of
      the 5'-end of the Shine-Dalgarno sequence while the other one allowed for
      labeling of the ribosome at the 5'-end side of the initiation AUG codon in the P
      site. According to the second approach, 5-azidouridine (5N3U) was randomly
      incorporated into mRNA transcripts during a T7 RNA polymerase catalyzed reaction
      by using a mixture of 5N3UTP and UTP. A message that had U residues at either -4,
      -3, -1, +2 and +14, +19, +20 positions was used (A from cro AUG is +1). Whereas
      cross-links with the 5N3U transcripts were essentially 'zero-length', the 5'
      derivatized transcripts were covalently attached to ribosomal components about 14
      A from the 5'-end. We found that proteins S1, S7, S5, S3 and S4 compose, or were
      close to, the ribosomal mRNA-binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379080
TI  - Stabilization of standard platelet concentrates and minimization of the platelet
      storage lesion by a prostacyclin analogue.
AB  - Platelet concentrates were pretreated with a stable synthetic prostacyclin
      analogue (Iloprost) at two different concentrations before the second
      centrifugation step (pelleting step) of preparation. This resulted in loss of
      platelet sensitivity to aggregating agents. To mimic the situation after
      transfusion and to assess the reversibility of platelet inhibition, platelets
      were washed during and after storage and resuspended in fresh-frozen autologous
      plasma. The Iloprost-treated and washed platelets exhibited an increased
      sensitivity to the aggregating agents, compared with the control platelets (p
      less than 0.01). Post-storage recovery of the synergistic aggregation was more
      than 80% of prestorage aggregation. Beta-thromboglobulin (beta TG) release and
      thromboxane B2 (TXB2) formation were significantly inhibited in Iloprost-treated
      platelets (p less than 0.01). After the second centrifugation step, beta TG
      release was 0.7% +/- 0.3%, compared with 2.7% +/- 0.9% for the controls. TXB2 was
      99 +/- 91 pg/ml, compared with 495 +/- 356 pg/ml for the controls. Platelet
      morphology and ultrastructure were well preserved during 5-day storage. In
      addition, Iloprost exerted a cytoprotective effect, as evidenced by the
      significant reduction in lactate dehydrogenase leakage. Post-storage LDH was 378
      +/- 159 and 415 +/- 239 U/l respectively by the two Iloprost concentrations,
      compared with 1180 +/- 937 U/l for the control platelets. The inhibitory and
      cytoprotective effects of Iloprost were sustained throughout storage, in contrast
      to the effect of PGE1 (Prostin) which was limited to the early phase of storage.

PMID- 1379081
TI  - Bayesian restoration of single-channel patch clamp recordings.
AB  - The technique of patch clamp recording makes possible the measurement of current
      flowing through a single ion channel in a cell membrane. Examination of such
      recordings suggests that the current is quantal in nature, alternating in a
      seemingly random manner between "on" and "off," but the recordings are corrupted
      by noise from a variety of sources. In this paper we propose and illustrate
      methods for restoring the underlying quantal signal from such noisy measurements.
      The methods use a Markov chain prior distribution for the underlying quantal
      process and base the restoration on the resulting posterior distribution.

PMID- 1379082
TI  - Hematopoietic growth factors upregulate the p65 type II interleukin-1 receptor on
      bone marrow progenitor cells in vitro.
AB  - Having previously shown that interleukin-1 (IL-1) induces the expression of IL-1
      receptors (IL-1Rs) on bone marrow (BM) cells in vivo through an indirect
      mechanism, we studied whether hematopoietic growth factors (HGFs) could induce
      the expression of IL-1R on BM cells in vitro. In vitro treatment of light-density
      murine BM (LDBM) cells with either IL-3, IL-6, granulocyte--colony-stimulating
      factor (CSF), or granulocyte-macrophage--CSF caused a 5- to 10-fold upregulation
      of IL-1R expression, whereas IL-1, IL-5, IL-7, and macrophage-CSF had no effect.
      Scatchard analysis showed one class of IL-1Rs on LDBM cells with an average of 66
      +/- 20 sites per cells. After 24 hours of treatment with IL-3, the number of IL
      1Rs increased to 413 +/- 125, without effecting the affinity. This effect
      required protein synthesis, but was independent of cell division. Purified
      lineage-negative progenitor cells (Lin-) did not express detectable levels of IL
      1R, but 24 hours of treatment with IL-3, GM-CSF, and G-CSF stimulated IL-1-
      specific binding. Autoradiographic analysis of Lin- cells showed that IL-1R
      induction by IL-3 occurs on undifferentiated blast cells. Affinity labeling of
      Lin- cells treated with HGFs showed an increase in a 65-Kd IL-1 binding protein
      that did not bind or compete with an anti-type I IL-1R antibody, suggesting that
      these cells expressed type II IL-1R. These data suggest that IL-1 stimulation of
      myelopoiesis occurs by a mechanism involving IL-1R upregulation on hematopoietic
      progenitor cells by HGFs.

PMID- 1379083
TI  - Specific repression of granulocyte-macrophage and granulocyte colony-stimulating
      factor gene expression in interleukin-1-stimulated endothelial cells with
      antisense oligodeoxynucleotides.
AB  - Antisense oligodeoxynucleotides (ODNs) have been used to effect the specific
      inhibition of cellular gene expression. We have evaluated the application of this
      approach to the inhibition of interleukin-1 (IL-1)-induced granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G
      CSF) expression in cultured human umbilical vein endothelial cells. Antisense
      ODNs or control ODNs (sense ODNs or missense ODNs containing random base
      substitutions) were added to cultures of endothelial cells, the cells were
      induced with IL-1 alpha, and the conditioned media were assayed for GM-CSF and G
      CSF by quantitative bioassays and for immunoreactive GM-CSF by enzyme
      immunoassay. Antisense ODNs complementary to the first 15 or 18 bases of the
      translation start sites of GM-CSF or G-CSF mRNAs inhibited, in a concentration
      dependent fashion, the IL-1-stimulated expression of the corresponding factor,
      but did not affect expression of the other factor. Control ODNs did not affect GM
      CSF or G-CSF expression. Exposure to a GM-CSF antisense ODN, but not a control
      ODN, substantially reduced cytoplasmic GM-CSF mRNA levels in IL-1-stimulated
      endothelial cells. Neither ODN affected levels of endothelial leukocyte adhesion
      molecule (ELAM)1 or glyceraldehyde-3-phosphate dehydrogenase mRNAs. We conclude
      that antisense ODNs complementary to the translation start sites of GM-CSF or G
      CSF mRNAs inhibit expression of the corresponding factor in a sequence-specific
      fashion and this effect is mediated, at least in part, by reduction in the
      cytoplasmic level of the targeted mRNA. Moreover, IL-1-induced GM-CSF or G-CSF
      expression does not depend on expression of the other factor.

PMID- 1379084
TI  - Type beta transforming growth factors promote interleukin-3 (IL-3)-dependent
      differentiation of human basophils but inhibit IL-3-dependent differentiation of
      human eosinophils.
AB  - Basophils and eosinophils share a common differentiation pathway. Factors
      regulating terminal commitment toward one cell type, however, have so far not
      been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both
      human eosinophils and basophils. In the present study, the effects of various
      recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils
      and basophils were studied in a bone marrow (BM) suspension culture system
      (normal donors, n = 13). We found that type beta transforming growth factors
      (TGFs) lead to a significant increase in the absolute numbers of basophils in BM
      cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL
      3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in
      the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/-
      37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta
      TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4
      +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and
      formation of eosinophil cationic protein in the same culture system. The effect
      of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and
      eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10
      ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody
      specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha)
      and IFN-gamma were found to downregulate IL-3-dependent formation of both
      basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65
      +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 +
      IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05])
      in our culture system. Type beta TGFs as well as the IFNs failed to directly
      induce differentiation of human basophils or eosinophils in the absence of other
      growth factors. Together, these results show that type beta TGFs and IFNs are
      potent regulators of cytokine-dependent growth and differentiation of human
      allergic effector cells.

PMID- 1379085
TI  - Stem cell factor induction of in vitro murine hematopoietic colony formation by
      "subliminal" cytokine combinations: the role of "anchor factors".
AB  - The high levels of hematopoietic growth factors required for in vitro and in vivo
      activity raise questions as to their role in normal hematopoietic maintenance. We
      hypothesize that the use of combinations of cytokines to stimulate hematopoietic
      progenitors might allow individual factors to exert their influence at lower,
      more physiologically relevant concentrations. Growth factor combinations were
      assessed by their ability to stimulate both total colonies and high proliferative
      potential colony-forming cells (HPP-CFC), an early murine hematopoietic
      progenitor, in double-layer agar cultures. Very-low-level combinations of colony
      stimulating factor (CSF)-1, granulocyte CSF (G-CSF), granulocyte-macrophage CSF
      (GM-CSF), interleukin (IL)-1 alpha, and IL-3 had little or no clonogenic
      capacity. Plateau levels of rr stem cell factor (rrSCF), a c-kit ligand, used
      alone also had negligible clonogenic capacity, but when combined with the low
      level combination of the other five factors produced total colony and HPP-CFC
      growth approaching that produced by all factors at plateau levels. Delayed
      addition experiments suggest that this effect may represent sequential activity
      of SCF and the other factors. We propose a model of the normal hematopoietic
      microenvironment in which SCF at locally high concentration on the stromal cell
      surface "anchors" the hematopoietic stem cell's response to multiple other
      cytokines at physiologically relevant levels.

PMID- 1379086
TI  - Interleukin-2-activated natural killer cells can support hematopoiesis in vitro
      and promote marrow engraftment in vivo.
AB  - Purified natural killer (NK) cells were obtained from mice with severe combined
      immune deficiency (SCID) to ascertain their effect on hematopoiesis. When
      activated and propagated with recombinant human interleukin-2 (rhIL-2) in vitro,
      SCID spleen cells maintained a phenotypic and lytic spectrum consistent with a
      pure population of activated NK cells. When added with syngeneic bone marrow
      cells (BMC) in soft agar, the activated NK cells could support hematopoietic
      growth in vitro without the addition of exogenous hematopoietic growth factors.
      However, when syngeneic BMC were added along with cytokines to produce optimal
      growth conditions, the addition of NK cells was then inhibitory for hematopoietic
      colony formation. Antibodies to interferon-gamma (IFN-gamma) partially reversed
      the inhibitory effects. Supernatants from the NK-cell cultures could also exert
      these effects on hematopoiesis, although to a lesser extent. Analysis of the NK
      cell RNA demonstrated that activated NK cells express genes for hematopoietic
      growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF),
      granulocyte CSF (G-CSF), and IL-1 beta. The NK cells were also found to express
      IFN-gamma, transforming growth factor-beta 1 (TGF-beta 1), and tumor necrosis
      factor-alpha (TNF-alpha) mRNA. Analysis of the NK-cell supernatants using factor
      dependent myeloid progenitor cell lines showed that the NK cells were producing G
      CSF and growth-promoting activity that could not be attributed to IL-1, IL-3, IL
      4, IL-5, IL-6, GM-CSF, G-CSF, macrophage CSF (M-CSF), or stem cell factor. The
      transfer of activated NK cells with BMC into lethally irradiated syngeneic mice
      resulted in greater BMC engraftment in the recipients. Thus, these results using
      a pure population of activated NK cells indicate that when activated, these cells
      can produce a variety of growth factors for hematopoiesis and exert significant
      hematopoietic growth-promoting effects in vivo.

PMID- 1379087
TI  - Induction of colony-stimulating factor receptor expression on hematopoietic
      progenitor cells: proposed mechanism for growth factor synergism.
AB  - In many cells systems, the cellular interaction between two or more humoral
      factors leads to a synergistic response in terms of cellular growth and function.
      In particular, the growth and differentiation of hematopoietic progenitor cells
      involves numerous synergistic interactions between colony-stimulating factors
      (CSFs) that individually stimulate hematopoiesis (granulocyte-CSF, granulocyte
      macrophage-CSF, and interleukin-3 [IL-3]), as well as between these factors and
      other cytokines that individually have no proliferative effect on progenitor cell
      growth (IL-1 and IL-6). The present study investigated whether hematopoietic
      growth factor (HGF) synergy could be mediated by upregulation of CSF receptors.
      Synergistic effects on bone marrow (BM) progenitor cell colony formation,
      regardless of the combination of factors used, were consistently preceded by
      increased CSF receptor expression on highly enriched BM progenitor cells, but not
      on unfractionated BM cells. Induction of CSF receptors preceded detectable
      differentiation and did not require cell division because nocodazole, an
      inhibitor of mitosis, blocked CSF-mediated cell proliferation, but not receptor
      upregulation. Furthermore, combinations of cytokines that did not synergize also
      failed to affect the level of CSF receptors on BM progenitors. These results have
      led us to propose a model for HGF synergy whereby one mechanism of action the
      investigated synergistic cytokines might be the ability to induce increased
      expression of CSF receptors.

PMID- 1379088
TI  - Differentiation and functional activity of human eosinophilic cells from an
      eosinophil HL-60 subline: response to recombinant hematopoietic growth factors.
AB  - We studied the effect of hematopoietic growth factors (granulocyte-macrophage
      colony-stimulating factor [GM-CSF], granulocyte [G]-CSF, interleukin (IL)-1, IL
      3, IL-5, IL-6, and macrophage [M]-CSF) on differentiation and functional activity
      of human eosinophilic HL-60 cells (Eos-HL-60) and compared them with effects on
      parental HL-60 promyelocytic leukemia cells. Purified biosynthetic GM-CSF and IL
      5 enhanced cell proliferation and induced eosinophilic differentiation in the
      eosinophilic subline in both liquid and agar cultures. IL-3 and IL-6 stimulated
      cell proliferation but had no effect on cell differentiation, whereas IL-1 and G
      CSF affected neither differentiation nor proliferation of Eos-HL-60 cells under
      the conditions tested. GM-CSF-, IL-3-, and IL-5-treated Eos-HL-60 cells showed
      increased O2- production in response to phorbol esters (PMA), enhanced
      phagocytosis of Candida albicans, and release of the enzymes arylsulfatase, beta
      glucuronidase and eosinophil peroxidase (EPO). The degranulation of eosinophils
      induced by GM-CSF, IL-5, and IL-3 may have relevance to the potential clinical
      toxicity of these hematopoietins, which also stimulate eosinophilopoiesis. G-CSF
      had no effect on enzyme release, oxidative metabolism, or phagocytic capacity of
      Eos-HL-60 cells. IL-5 did not affect proliferation, differentiation, or enzyme
      release in promyelocytic HL-60 cells. These results indicate the specificity of
      IL-5 for the eosinophil lineage, confirm the effects of GM-CSF and IL-3 on
      eosinophilopoiesis and mature eosinophil function in a model system, and indicate
      the absence of G-CSF and IL-1 stimulation of eosinophils. The Eos-HL-60 line is a
      useful model for studying human eosinophil responses to cytokines.

PMID- 1379089
TI  - Molecular cloning and analysis of in vivo expression of murine P-selectin.
AB  - P-selectin (CD62) is a rapidly inducible cell surface adhesion molecule that is
      expressed on platelets and endothelial cells and mediates their interaction with
      leukocytes. In vitro studies have suggested that this receptor may play an
      important role in hemostasis and in inflammatory response to tissue injury. We
      report the molecular cloning and sequencing of murine cDNA for P-selectin. The
      lectin, epidermal growth factor (EGF)-like, transmembrane, and cytoplasmic
      domains are highly conserved between mouse and human, with an overall amino acid
      identity of 79%. To further investigate the biology of this adhesion molecule in
      vivo, we analyzed mRNA levels for P-selectin in mice after injection with
      endotoxin. Northern blot data indicate that the cellular response in vivo
      includes a rapid increase in the level of mRNA, presumably for new synthesis of P
      selectin. The increase in mRNA is maximal at 4 hours, and turnover is relatively
      rapid, with levels of RNA having decreased substantially by 6 hours following
      stimulation with endotoxin. After administration of endotoxin, the highest levels
      of mRNA expression were detected in liver, lung, kidney, and heart.

PMID- 1379090
TI  - Fetal hemoglobin levels in sickle cell disease and normal individuals are
      partially controlled by an X-linked gene located at Xp22.2.
AB  - Fetal hemoglobin (Hb F) production in sickle cell (SS) disease and in normal
      individuals varies over a 20-fold range and is under genetic control. Previous
      studies suggested that variant Hb F levels might be controlled by genetic loci
      separate from the beta-globin complex on chromosome 11. Using microscopic radial
      immunodiffusion and flow cytometric immunofluorescent assays to determine the
      percentage of F reticulocytes and F cells in SS and nonanemic individuals, we
      observed that F-cell levels were significantly higher in nonanemic females than
      males (mean +/- SD, 3.8% +/- 3.2% v 2.7% +/- 2.3%). F-cell production as
      determined by F reticulocyte levels in SS females was also higher than in SS
      males (17% +/- 10% v 13% +/- 8%). We tested the hypothesis that F-cell production
      in both normal and anemic SS individuals was controlled by an X-linked locus with
      two alleles, high (H) and low (L). Using an algorithm to determine the 99.8%
      confidence interval of a normal distribution in nonanemic individuals, we
      estimated that males and females with at least one H allele had greater than 3.3%
      F cells. Comparisons of male-male or female-female SS sib pairs with discordant F
      reticulocyte levels distinguished two phenotypes in SS males (L, less than 12%;
      H, greater than 12%) and three phenotypes in SS females (LL, less than 12%; HL,
      12% to 24%, HH greater than 24%). Linkage analysis using polymorphic restriction
      sites along the X chromosome in eight SS and one AA family localized the F-cell
      production (FCP) locus to Xp22.2, with a maximum lod score (logarithm of odds of
      linkage v independent assortment) of 4.6 at a recombination fraction of 0.04.

PMID- 1379091
TI  - Application of automatic image analysis for quantitative morphological studies of
      peroxisomes in rat liver in conjunction with cytochemical staining with 3-3'
      diaminobenzidine and immunocytochemistry.
AB  - We describe the application of automatic image analysis for quantitative
      morphological studies of peroxisomes in rat liver. For automatic detection by
      light and electron microscopy peroxisomes must be stained with the alkaline DAB
      procedure for catalase. There is a good agreement between the results obtained by
      conventional morphometric techniques and by automatic image analysis of DAB
      stained electron microscopic preparations. Moreover, the image analyzer may be
      used in conjunction with a light microscope for evaluation of semithin sections
      (1-0.25 microns), provided the section thickness factor is taken into
      consideration. This latter approach has proven highly efficient in estimation of
      peroxisome proliferation. The limitations of this method and the relevance of
      volume density as a reliable morphometric parameter for evaluation of peroxisome
      proliferation are discussed. In the second part of this study we present the
      application of image analysis for quantitation of alterations of individual
      peroxisomal enzyme proteins after treatment with bezafibrate in immunogold
      stained ultrathin sections. There is good agreement between the results of
      quantitative immunocytochemistry and Western (immuno) blot analysis of highly
      purified peroxisomal fractions. In our experience quantitative immunoelectron
      microscopy provides a versatile, highly sensitive, and efficient method for
      detection of modulations of various proteins in peroxisomes. Finally the
      limitations and prospects of quantitative immunocytochemistry for investigation
      of peroxisomal proteins are discussed.

PMID- 1379092
TI  - Comparative mapping of mouse chromosome 4 and human chromosome 9: Lv, Orm, and
      Hxb are closely linked on mouse chromosome 4.
AB  - The genes for orosomucoid (ORM-1 and ORM-2), delta-aminolevulinate dehydratase
      (ALAD), and hexabrachion or tenascin (HXB) all map to the q31-qter region of
      human Chromosome (Chr) 9. The mouse homolog of each of these genes has been
      mapped to Chr4, but hexabrachion has not previously been mapped by linkage
      analysis. We have now ordered Orm-1, Lv (the mouse homolog of ALAD), and Hxb in
      an interspecific backcross panel, by use of tyrosinase related protein-1, Tyrp-1,
      whose human homolog maps to 9p13-pter (Abbott et al., Genomics 1991) as a
      reference locus. No recombinants were identified in 124 animals between Lv and
      Orm-1. Hxb was found to be 1.6 cM distal to Lv and Orm-1, and 4.8 cM proximal to
      Tyrp-1, or b. These data therefore contribute to our knowledge of the conserved
      synteny between HSA 9q and MMU 4.

PMID- 1379094
TI  - First trimester concentrations of pregnancy associated plasma protein A and
      placental protein 14 in Down's syndrome.

PMID- 1379093
TI  - Effects of chronic amitriptyline administration on saliva from the parotid and
      submandibular glands of the rat.
AB  - The effect of prolonged treatment with amitriptyline on the secretory activity of
      rat salivary glands evoked by parasympathetic nerve stimulation and isoprenaline
      administration has been studied. Low doses of amitriptyline (10 mg/kg per day for
      2 or 4 weeks), did not significantly affect salivary flow evoked by either
      parasympathetic nerve or isoprenaline stimulation. Higher doses of amitriptyline
      (50 mg/kg/day for 2 or 4 weeks) however, markedly decreased parasympathetic
      evoked salivary secretion (flow and volume) from both parotid and submandibular
      glands, while isoprenaline-evoked secretions were unaffected. Sodium, potassium,
      and calcium concentrations of nerve-elicited or isoprenaline-evoked saliva were
      not significantly altered by amitriptyline treatment. Protein concentration and
      amylase activity of nerve-elicited parotid saliva were, however, greatly
      increased by chronic amitriptyline administration. Possible mechanisms for drug
      induced increase in nerve-elicited salivary protein concentration include changes
      in cholinergic receptor binding, release of neuropeptides and variations in
      phosphatidylinositol turnover, which need further study.

PMID- 1379095
TI  - Management of breast cancer.

PMID- 1379096
TI  - Reprocessing data to form QALYs.
AB  - OBJECTIVES: To determine whether reprocessing data from published sources into
      quality adjusted life years (QALYs), as recommended in The QALY Toolkit, is a
      useful method of helping purchasing authorities to determine the most cost
      effective pattern of care to buy for their populations. SETTING: United Kingdom.
      DESIGN: The method was tested for six elective surgical conditions; data from
      published studies were reprocessed into the Rosser index, to obtain values for
      change in quality of life. These were then used to form QALYs. A small validation
      exercise was carried out. MAIN OUTCOME MEASURES: QALYs formed from the Rosser
      index. RESULTS: Published data could not be found for three interventions
      (cataract surgery, inguinal hernia repair, varicose vein surgery). For the
      remainder (prostatectomy, hip replacement, and knee replacement) data were found
      which could be reprocessed to form QALYs, though it was often hard to compare
      data from different studies and many assumptions had to be made. CONCLUSION: The
      value of QALY results obtained by this method is questionable, given the large
      number of assumptions which had to be made. For many interventions published data
      are unlikely to be available.

PMID- 1379097
TI  - The development of new techniques in the assessment and monitoring of recovery
      from severe head injury: a preliminary report and case history.
AB  - The case of a 19-year-old male who sustained a severe brain injury is described.
      This patient was initially given a very gloomy prognosis, leading to poor
      expectations for recovery. Additionally, like many such patients in the United
      Kingdom, he was cared for by a ward team who were without specialized training in
      head injury rehabilitation. Despite these factors the patient went on to make a
      good recovery. The issues of specialized care and the need for more appropriate
      patient assessment procedures are raised. The MRC Head Injury Assessment Project
      is described.

PMID- 1379098
TI  - Neural changes in acute arthritis in monkeys. III. Changes in substance P,
      calcitonin gene-related peptide and glutamate in the dorsal horn of the spinal
      cord.
AB  - The effects of an experimentally induced arthritis on immunoreactivity of
      putative primary afferents neurotransmitter/neuromodulators were examined.
      Immunoreactive staining for substance P (SP), calcitonin gene-related peptide
      (CGRP) and glutamate (Glu) in the monkey dorsal horn was examined following
      inflammation of one knee joint induced by injection of 5% kaolin and 5%
      carrageenan. Spinal cords were examined at different time periods after induction
      of arthritis (2.5, 4, 6 and 8 h). Side to side differences in immunoreactivity
      were determined by a computer assisted quantitation system. A significant overall
      decrease in immunoreactivity of the lumbar versus the cervical dorsal horn was
      found for SP. The decrease for SP showed maximal changes of 68.3% at 4 h and
      54.7% at 6 h. Immunoreactivity for CGRP was decreased 31.5% at 8 h and variable
      at other time points. Immunoreactivity for Glu, showed an ipsilateral increase of
      31.4% at 4 h, 33.7% at 6 h, 39.9% at 8 h and a significant effect for lumbar
      versus cervical. Repetitive peripheral stimulation of the joint was shown to be
      important for changes in SP and Glu immunoreactivity. Without frequent peripheral
      stimulation in the early stages of the development of arthritis, SP showed no
      quantitative side to side differences. Increases in Glu immunoreactivity were
      present but not as prominent with minimal joint manipulation. These studies
      suggest that Glu may be involved in the aching pain of inflammation at rest
      whereas SP, CGRP and Glu may mediate pain induced by joint movement.

PMID- 1379099
TI  - Causes and consequences of intrauterine growth retardation in Latin America.
AB  - The purpose of this article is to present a critical review of the literature on
      the causes and consequences of intrauterine growth retardation (IUGR) and of body
      proportions at birth among IUGR infants. IUGR is generally defined as a birth
      weight below the tenth percentile of a reference weight distribution according to
      gestational age. Chronic maternal malnutrition and other poverty-related factors
      are likely to be important determinants of IUGR in developing countries. IUGR has
      been associated with increased risks of neonatal morbidity and mortality and
      alterations in physical and mental development during early childhood. IUGR
      newborns can be classified as "symmetric" or "asymmetric" in terms of body
      proportionality. The available literature indicates that the risk of perinatal
      morbidity is higher among asymmetric newborns than among their symmetric
      counterparts, while symmetric newborns confront a higher risk of impaired
      physical and mental development. Obviously, the clinical and statistical
      usefulness of these IUGR and body proportionality assessments depends on the
      accuracy of the birth measurements (length, weight, and estimated gestational
      age) from which they are derived. Latin America now has the hospital
      infrastructure needed to obtain reliable birth data of this kind. It is important
      to use these resources effectively in order to improve the health assessment of
      newborns and gain a better understanding of the causes and consequences of IUGR.

PMID- 1379100
TI  - Open or transurethral surgery for the large prostate gland.
AB  - A comparative study of transurethral (TUR) and open prostatectomy for the large
      prostate gland has been carried out. Over a 5-year period 94 transurethral
      resections and 73 open procedures were performed for prostate glands weighing
      more than 50 g. There was a single death in each group, giving relative mortality
      rates of 1.1% TUR and 1.4% open. The post-operative hospital stay was
      significantly shorter in the TUR group. The open group suffered significantly
      more complications in the first week but the TUR patients, although having fewer
      immediate postoperative complications, had significantly more in the first year,
      so that overall complication rates were similar (35% vs 36%). Patient
      satisfaction was equal in both groups.

PMID- 1379101
TI  - Laser ablation of the prostate in patients with benign prostatic hypertrophy.
AB  - Seventeen patients with bladder neck obstruction due to benign prostatic
      hypertrophy have been treated with the Neodymium: YAG laser. We review our
      experience since the first patient was treated in September 1990. Using a
      prototype deflecting gold alloy tip on a quartz laser fibre (Lateralase TM), we
      ablated obstructing prostatic adenoma and constricting bladder neck tissue.
      Experience with this technique has enabled a patient population to be defined in
      whom laser therapy for prostatic obstruction may be effective. The treatment is
      relatively simple, speedy and attended by virtually no blood loss. Laser ablation
      therapy may offer some advantages over conventional transurethral resection of
      the prostate (TURP) in a selected subgroup of patients. The advent of new
      delivery systems may make laser ablation therapy a practical alternative to TURP.

PMID- 1379103
TI  - Re: Determination of pre-orchiectomy serum levels of alpha-fetoprotein and human
      choriogonadotrophin in testicular cancer. Sophie D. Fossa and M. Mason. Br. J.
      Urol., 69, 108, 1992.

PMID- 1379102
TI  - P53 and Ki-67 immunoreactivity in human prostate cancer and benign hyperplasia.
AB  - Mutation of the p53 gene is one of the commonest genetic abnormalities found in
      solid human tumours. This gene is probably concerned with the control of cellular
      proliferation and in view of this we carried out a study of human prostate cancer
      and benign prostatic hyperplasia, comparing the expression of mutated p53 with
      measurement of growth fractions as assessed by staining with Ki-67. A series of
      29 patients with prostate cancer (CaP) were compared with 34 men with benign
      hyperplasia (BPH); 22 of 29 prostate cancers (76%) contained Ki-67
      immunoreactivity compared with 10 of 34 (29%) BPH. With respect to p53 staining,
      significantly more prostate cancers (17%) were stained than BPH (0%). The mean Ki
      67 score in cancers positive for p53 (4.3%) was greater than that found in
      cancers negative for p53 (1.2%), but no statistically significant relationship
      was found between tumour grade and Ki-67 staining. The use of Ki-67 and p53
      staining may allow identification of tumours with a higher rate of cell growth
      and may permit development of prognostic factors.

PMID- 1379104
TI  - Survey of urological centres and review of current practice in the pre-operative
      assessment of prostatism.
AB  - A survey of 24 urological centres has shown a wide variation in the routine pre
      operative assessment of patients being considered for prostatectomy. Imaging of
      the urinary tract by intravenous urography (IVU) or ultrasound (US) is performed
      in 21/24 centres (79%) and plain films in 16/24 (67%). Post-micturition residual
      volume (PMRV) is estimated quantitatively in 10/24 centers (42%). Although there
      is little agreement on what constitutes a significant PMRV, a large PMRV leads to
      increased likelihood of operation, and earlier operation. Peak urine flow rate (Q
      max) is measured in 19/24 centres (79%). The significance of these findings is
      discussed.

PMID- 1379105
TI  - Is pre-operative imaging of the urinary tract worthwhile in the assessment of
      prostatism?
AB  - The reports of routine pre-operative imaging investigations performed on patients
      presenting with symptoms of uncomplicated benign prostatic hypertrophy were
      compared with management decisions and clinical outcome. In 175 patients with
      prostatism no urological abnormality which altered management was discovered on
      plain films of the abdomen and pelvis and ultrasound of the urinary tract which
      were performed routinely. Post-micturition residual volume (PMRV), estimated by
      ultrasound, was compared with the maximum urine flow rate (Q max) in 57 patients.
      PMRV showed negative correlation with Q max. Both high PMRV and low Q max were
      associated with the urologist's decision to operate, but multiple logistic
      regression revealed that ultrasound residual volume was not a significant
      predictor of operation when adjusted for Q max. Urologists in this hospital
      therefore use flow rates as the primary indication of the need to operate. We
      suggest that no routine pre-operative imaging need be performed in patients
      presenting with prostatism.

PMID- 1379106
TI  - Urinary flow rates in patients with benign prostatic hypertrophy following
      treatment with alfuzosin. DUALF Group.
AB  - In order to document further the onset of action of alfuzosin, a selective alpha
      1 blocker, 93 symptomatic patients with benign prostatic hypertrophy were
      randomly allocated to a single oral dose of either alfuzosin 1.25 mg or 2.5 mg,
      or placebo, after a 1-week placebo lead-in period. The effects on flow rates were
      assessed 1 h 30 min after administration. Peak and mean flow rates were
      significantly increased in the alfuzosin groups, as compared with placebo, in a
      dose-dependent manner. After a single intake of placebo, the mean values of these
      2 parameters showed little change. The effect on the cardiovascular system (heart
      rate and blood pressure) was mild. This study indicates that the action of
      alfuzosin is already present 1 h 30 min after administration.

PMID- 1379107
TI  - Finasteride in the treatment of benign prostatic hyperplasia. A urodynamic
      evaluation.
AB  - A group of 69 men with bladder outflow obstruction due to benign prostatic
      hyperplasia (BPH) were treated in a double-blind, placebo-controlled study with
      finasteride (Proscar, MK-906), a 5-alpha reductase inhibitor, 5 mg or 10 mg/day
      or placebo for 3 months; subsequently, 20 patients received finasteride 5 mg/day
      for a further 9 months in an open extension study. In treated patients
      dihydrotestosterone declined by over 60%, remaining unchanged with placebo.
      Symptom scores fell significantly in all 3 groups. Mean maximum flow rates fell
      slightly in placebo-treated patients but improved by 1.5 ml/s in the 10 mg group
      and by 3.3 ml/s in the 5 mg group. After 1 year's treatment, the reduction in
      symptom score and increase in flow rate were well maintained; the mean prostate
      volume was reduced by 14% and prostatic specific antigen declined by 28%. It was
      concluded that finasteride shows some efficacy in the treatment of BPH, with
      minimal toxicity, but 12 months of therapy or longer may be necessary to achieve
      maximal effect.

PMID- 1379109
TI  - Galanin-evoked acetylcholine release in the rat striatum is blocked by the
      putative galanin antagonist M15.
AB  - The effect of the putative galanin (GAL) antagonist M15 on the Gal-evoked release
      of acetylcholine (ACh) was investigated in the rat striatum using microdialysis
      and HPLC techniques. GAL (3 nmol/10 microliters), applied in the lateral
      ventricle (i.c.v.) or perfused through the microdialysis membrane into the
      striatum, was found to enhance basal ACh release. The GAL-evoked release of
      striatal ACh was completely blocked by M15 (3 nmol/10 microliters), administered
      either i.c.v. or into the straitum. This finding suggests that GAL stimulates the
      basal ACh release in the rat striatum by a direct action of the peptide on
      striatal GAL receptors.

PMID- 1379108
TI  - Calcitonin gene-related peptide enhances substance P-induced behaviors via
      metabolic inhibition: in vivo evidence for a new mechanism of neuromodulation.
AB  - The present study examined the effects of intrathecal (i.t.) injection of
      calcitonin gene-related peptide (CGRP) on caudally directed biting and scratching
      induced by i.t. substance P (SP), bombesin (BBS), strychnine (STR), and kainic
      acid (KA). CGRP alone (5.25, 10.5 and 21 nmol) had no effect on these behaviors,
      but CGRP pretreatment produced a dose-related enhancement of behaviors induced by
      SP or BBS, but not by KA or STR. 2-Amino-5-phosphonovaleric acid (APV, 25 nmol),
      a selective N-methyl-D-aspartate (NMDA) receptor antagonist, did not block the
      CGRP potentiation of SP and BBS induced behaviors. CGRP, however, failed to
      enhance scratching and biting induced by a SP analogue [pGlu5-Mephe8-MeGly9]SP(5
      11) (Dime-C7) that is resistant to enzymatic degradation by SP endopeptidase.
      These findings demonstrate that CGRP potentiates SP induced behavioral responses
      via inhibition of neuropeptide degradation and that this mechanism may serve as a
      physiological mechanism of SP modulation.

PMID- 1379110
TI  - Modulation of synaptic efficacy in field CA1 of the rat hippocampus by forskolin.
AB  - Activation of cAMP-dependent protein kinase (kinase A) has recently been shown to
      enhance responses evoked by stimulation of alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionate (AMPA) receptors in cultured hippocampal pyramidal neurons.
      Here we report results of experiments designed to determine if activation of the
      cAMP cascade potentiates synaptic strength in field CA1 of rat hippocampal
      slices. We find that bath application of the direct adenylate cyclase activator
      forskolin (50 microM) enhances the field excitatory postsynaptic potential (EPSP)
      slope and population spike amplitude evoked by stimulation of
      Schaffer/commissural afferents. This effect is potentiated by the
      phosphodiesterase inhibitor and adenosine receptor antagonist 3-isobutyl-1
      methylxanthine (IBMX). The enhancement produced by forskolin is suppressed in the
      presence of adenylate cyclase inhibitors and is not mimicked by the inactive
      forskolin analogue 1,9-dideoxyforskolin, indicating that, indeed, activation of
      adenylate cyclase mediates the effects of forskolin in field CA1. Our
      observations support the idea that changes in intracellular cAMP levels can
      modulate synaptic efficacy of excitatory glutamatergic synapses in the mammalian
      hippocampus.

PMID- 1379111
TI  - In vivo studies on the enhancement of serotonin reuptake by tianeptine.
AB  - The present study investigates the in vivo effects of the serotonin uptake
      enhancer tianeptine. The serotonin metabolite, 5-hydroxy-indolacetic acid (5
      HIAA) was measured by in vivo voltammetry and carbon fiber electrodes chronically
      implanted in different brain areas of freely moving rats. Tianeptine (10 mg/kg
      i.p.) increased extracellular 5-HIAA in the hippocampus and hypothalamus. The
      interaction between tianeptine and drugs known to interfere with the uptake or
      release of serotonin (sertraline, buspirone, D-norfenfluramine) was then studied
      and, to ascertain the in vivo pharmacological relevance of tianeptine's effects,
      its ability to reduce the serotoninergic syndrome was evaluated. Both the
      biochemical and behavioral data indicate that in vivo tianeptine's effects on the
      serotoninergic system are likely to be due to serotonin uptake enhancement.

PMID- 1379112
TI  - The effect of chronic atypical antipsychotic drugs and haloperidol on amphetamine
      induced dopamine release in vivo.
AB  - The effect of chronic administration of antipsychotic drugs (21 days in drinking
      water followed by 3 days drug washout) on the D-amphetamine (1.0 mg/kg, s.c.)
      induced increase in dopamine (DA) release in the striatum and the nucleus
      accumbens of awake, freely-moving rats was investigated with microdialysis.
      Chronic administration of haloperidol, a typical antipsychotic, (0.5 mg/kg/day),
      decreased basal extracellular DA release in the striatum and the nucleus
      accumbens but did not affect D-amphetamine-induced DA release in either region.
      In marked contrast, chronic administration of three atypical antipsychotic drugs:
      amperozide (2 mg/kg/day), clozapine (10 mg/kg/day) and melperone (2 mg/kg/day)
      increased basal extracellular DA and enhanced D-amphetamine-induced DA release in
      the striatum. In the nucleus accumbens, basal extracellular DA was decreased by
      chronic amperozide, unchanged by chronic clozapine and increased by chronic
      melperone. Most significantly, D-amphetamine-induced DA release was inhibited by
      chronic amperozide or clozapine, but unaffected by chronic melperone in this
      region. These results suggest that atypical antipsychotic drugs can alter DA
      release in a region specific manner. In particular, attenuation of amphetamine
      like stimulation of DA release with reduced basal DA release in the nucleus
      accumbens could contribute to the antipsychotic action of amperozide which has a
      very weak affinity for D2 DA receptors.

PMID- 1379113
TI  - Monoamine innervation of bed nucleus of stria terminalis: an electron microscopic
      investigation.
AB  - Immunocytochemical studies showed distinctive monoamine input to the bed nucleus
      of the stria terminalis (BST). A comparison of axons immunoreactive (IR) for a
      catecholamine synthetic enzyme [tyrosine hydroxylase (TH) or dopamine beta
      hydroxylase (DBH) or phenylethanolamine-N-methyl transferase (PNMT)] or serotonin
      (5-HT) was performed. TH-IR axons had a greater density in the lateral BST, but
      DBH-IR and 5-HT-IR axons had a greater density in the medial BST. PNMT-IR axons
      were dense in the intermediate BST. TH-IR axons had a greater density than DBH-
      and PNMT-IR axons in the dorsolateral BST, but DBH-IR axons had the greatest
      density in the ventrolateral BST. Ultrastructural studies revealed that TH-IR
      terminals formed synapses with soma, dendrites, spines, and axons in the
      dorsolateral BST. DBH-IR terminals formed synapses with dendritic shafts and
      spines, and 5-HT-IR terminals formed synapses with dendrites in the ventrolateral
      BST. Only some 5-HT-IR axons were myelinated. The medial vs. lateral organization
      of the noradrenergic and dopaminergic afferents in the BST of the rat brain is
      now evident and is similar to the human brain. The medial-lateral functional
      subdivision of the BST is supported by the pattern of dopaminergic,
      noradrenergic, and serotonergic afferents. This demonstration of epinephrine
      producing afferents in the BST is the first detailed description of adrenergic
      input to the BST and aided the determination that catecholaminergic innervation
      of the ventrolateral BST is predominantly noradrenergic as has been proposed for
      many years. However, the additional demonstration of rich dopaminergic
      innervation of the dorsolateral subnucleus suggests further division of the BST
      into dorsal and ventral functional subgroups.

PMID- 1379114
TI  - Early reference to air reduction of intussusception.

PMID- 1379115
TI  - Hematopoietic colony-stimulating factors. Uses in combination with standard
      chemotherapeutic regimens and in support of dose intensification.
AB  - BACKGROUND: Three hematopoietic colony-stimulating factors (CSF) are currently
      approved for clinical use and several more are being used in clinical trials.
      These factors have impressive quantitative and/or functional effects on their
      respective target cell lines, but their best clinical uses have not been defined.
      METHODS: The literature regarding the use of CSF in standard chemotherapy is
      reviewed data and from early Phase I-II studies the use of granulocyte-macrophage
      CSF (GM-CSF) in support of dose intensification without progenitor cell
      replacement are presented. Dose intensive cyclophosphamide (5000 mg/m2),
      etoposide (1500 mg/m2), and cisplatin (150 mg/m2) (DICEP) were administered
      during 3 days, followed by CSF until hematologic recovery was achieved. Patients
      had advanced types of cancer unlikely to respond to standard chemotherapy.
      RESULTS: CSF can shorten the duration of leukocyte nadirs when given with
      standard chemotherapy, but a benefit to patients in terms of improved survival or
      quality of life has not been shown. Dose intensification has increased partial
      and complete response rates in several tumor types. The higher complete remission
      rate may translate into improved survival; no convincing data have been published
      to date supporting that possibility. The duration of severe leukopenia (absolute
      neutrophil count, less than 100/microliters) after DICEP can be shortened from
      8.5 days to 5-6 days with either granulocyte CSF (G-CSF) or GM-CSF. GM-CSF has
      been shown to decrease the duration of hospital stay from 18.7 to 9.6 days and to
      decrease the need for readmittance to the hospital for cytopenic fever. A high
      complete remission rate (35%) was seen in patients with breast cancer and durable
      complete remissions were achieved in patients with refractory non-Hodgkin
      lymphoma. CONCLUSIONS: CSF shortens the duration of postchemotherapy leukocyte
      nadirs and allows maintenance of dose when this is essential for a beneficial
      outcome. Substantial dose escalations are also possible with CSF support and can
      produce a high complete response rate that offers hope for improved survival in
      selected patients.

PMID- 1379116
TI  - The interferons.
AB  - In the 10 years since the interferons (IFN) entered large-scale clinical trials,
      much has been learned much about their uses as single agents. alpha-IFN, the most
      widely studied, has shown antitumor and antiviral efficacy against various tumors
      and tumor-related viruses; it has been approved by the Food and Drug
      Administration for the treatment of patients with hairy cell leukemia, acquired
      immune deficiency syndrome-related Kaposi sarcoma, and condylomata acuminata.
      Although IFN are effective as single agents in certain clinical situations,
      increasing experience with these cytokines suggests that their greatest
      therapeutic potential may be in combination with other biologic response
      modifying, cytotoxic, or antiviral drugs. Trials combining alpha-IFN with 5
      fluorouracil to treat colorectal carcinoma or with zidovudine to treat acquired
      immune deficiency syndrome have shown the significant impact that IFN
      administered in conjunction with other carefully selected agents can have. To
      design the most effective combination regimens, better preclinical models that
      clarify the mechanisms of action of IFN and define their biochemical interactions
      with other agents are needed.

PMID- 1379117
TI  - The role of interferons in the treatment of solid tumors.
AB  - BACKGROUND: Originally described as antiviral agents, interferons (IFN) were
      investigated as potential anticancer agents because of their antiproliferative
      and cytotoxic effects, their ability to activate specific components of the
      immune system, and their relatively modest toxicities. Interest intensified when
      durable complete remissions were observed in patients with hairy cell leukemia
      after IFN treatment; modest, but reproducible activity also was found against
      tumors such as melanoma and renal cell carcinoma which are unresponsive to
      conventional chemotherapy. Observations of synergy between IFN and cytotoxic
      drugs in vitro and in vivo suggested that IFN may have additional utility as
      modulating agents. METHODS: Reports of major clinical trials using IFN either
      alone or in combination with other agents were reviewed. Activity was identified
      by disease site. Correlations were made with important preclinical studies.
      RESULTS: IFN has reproducible, but modest, single-agent activity against
      melanoma, renal cell carcinoma, and acquired immune deficiency syndrome-related
      Kaposi sarcoma. IFN may be useful in the treatment of a number of benign, in
      situ, or low-grade tumors. IFN in combinations with cytotoxic agents have
      demonstrated activity in solid tumors. Clinical trials using combinations of IFN
      and 5-fluorouracil or dacarbazine suggested a potential benefit for the
      combination compared with single-agent chemotherapy. These are preliminary
      findings that require confirmation, but they suggest that combination therapy
      should be investigated further. In early preclinical and clinical studies,
      combinations of IFN and other biologic agents, hormonal agents, and radiation
      therapy appear to be interesting. CONCLUSIONS: The role of IFN in the treatment
      of solid tumors may be evolving from that of single-agent therapy to combination
      therapy with other active agents. Additional studies are required to determine
      the optimal doses, schedules, and sequencing of these combination therapies.

PMID- 1379118
TI  - Development of glutathione S-transferase placental form (GST-P) stained foci
      during hamster buccal pouch mucosa carcinogenesis.
AB  - The expression of the placental form of glutathione S-transferase (GST-P) using
      anti-rat liver GST-P antibody was investigated in hamster buccal pouch mucosa
      (HBPM) treated with 0.5% dimethylbenz[a]anthracene (DMBA) biweekly for 12 weeks.
      This preliminary study showed that the anti-rat liver GST-P antibody is
      applicable to the HBPM model and that DMBA treatment induced GST-P positive foci.
      These foci are randomly distributed and frequently involved the hyperplastic and
      dysplastic segments of the epithelium, as well as squamous cell carcinoma.
      Further study is needed to explore the kinetics of these GST-P positive foci.

PMID- 1379120
TI  - Identification and characterization of new antigenic fragments related to
      carcinoembryonic antigen in adult feces.
AB  - Antigens in human adult feces related to carcinoembryonic antigen (CEA) were
      analyzed with respect to their molecular masses, CEA domain compositions, and N
      terminal amino acid sequences. By avoiding perchloric acid treatment, new fecal
      antigens related to CEA were identified. The fecal antigens revealed by Western
      blot were M(r) 78,000, 70,000, 60,000, 50,000, 44,000, 36,000, 33,000, and 25,000
      and a species M(r) less than or equal to 14,000. Unlike native CEA, all of the
      fecal antigens were very poorly soluble in perchloric acid and did not bind to
      concanavalin A, suggesting that they had undergone significant deglycosylation in
      the digestive tract. The major fecal antigens were purified by immunoaffinity
      chromatography and their N-terminal amino acid sequences determined. FA78, FA60,
      FA33, and the M(r) less than or equal to 14,000 antigen had the N-terminal amino
      acid sequence of the CEA N-domain, and FA44 and FA25, the sequence of the CEA A2
      domain. The CEA domain compositions of the fecal antigens were investigated by
      probing them with anti-CEA monoclonal antibodies of known domain specificities.
      The N-terminal amino acid sequences, immunoreactivities with anti-CEA monoclonal
      antibodies, and apparent molecular masses of the fecal antigens allowed the
      following domain assignments (based on CEA as N-A1B1-A2B2-A3B3): FA78, N-A1B1
      A2B2-A3B3; FA60, N-A1B1-A2B2; FA44, A2B2-A3B3; FA33, N-A1B1; and FA25, A2B2. The
      M(r) less than or equal to 14,000 antigen was shown to be the N-domain of CEA or
      nonspecific cross-reacting antigen. FA36 was assigned the N-AB domain structure
      of nonspecific cross-reacting antigen. The results suggested that FA78, FA60,
      FA44, FA33, and FA25 were degradation products (including deglycosylation and
      proteolysis) of CEA and that FA36 was a degradation product of nonspecific cross
      reacting antigen.

PMID- 1379119
TI  - Biochemical modulation of tumor cell energy: regression of advanced spontaneous
      murine breast tumors with a 5-fluorouracil-containing drug combination.
AB  - This report describes a highly active chemotherapeutic drug combination,
      consisting of N-(phosphonacetyl)-L-aspartate plus 6-methylmercaptopurine riboside
      plus 6-aminonicotinamide plus 5-fluorouracil, in CD8F1 mice bearing spontaneous,
      autochthonous, breast tumors or first-passage advanced transplants of these
      spontaneous tumors. The combination and sequence of administration of these drugs
      were selected on the basis of known potentiating biochemical interactions. High
      performance liquid chromatography and nuclear magnetic resonance spectroscopy
      measurements of biochemical changes resulting from treatment with N
      (phosphonacetyl)-L-aspartate plus 6-methylmercaptopurine riboside plus 6
      aminonicotinamide indicated a severe depletion of cellular energy levels in the
      treated tumors. 6-Aminonicotinamide produced a severe block of the pentose shunt,
      and 5-fluorouracil severely inhibited both thymidylate synthase and thymidine
      kinase in the treated tumors. This quadruple drug combination, administered on a
      10-11-day schedule, produced an impressive partial tumor regression rate of 67%
      of large, spontaneous, autochthonous, murine breast tumors and a tumor regression
      rate of 74% of first-passage transplants of the spontaneous breast tumors.

PMID- 1379121
TI  - Correlation between in vivo toxicity and preclinical in vitro parameters for the
      immunotoxin anti-B4-blocked ricin.
AB  - Anti-B4-blocked ricin (Anti-B4-bR) is an immunotoxin comprised of the anti-B4
      monoclonal antibody and the protein toxin, "blocked ricin." In blocked ricin, the
      galactose-binding sites of the ricin B-chain which mediate nonspecific binding to
      cells are blocked by covalently linked affinity ligands prepared from N-linked
      oligosaccharides of fetuin. Blocked ricin consists of two species, one with two
      covalently attached ligands and one with three covalently attached ligands. In a
      Phase I dose escalation clinical trial, Anti-B4-bR was administered to patients
      with relapsed and refractory B-cell neoplasms by 7-day continuous infusion.
      Although several different lots of Anti-B4-bR had similar IC37 values as
      determined by in vitro cytotoxicity testing on cultured human cell lines, these
      lots differed in their in vivo toxicity when administered to patients. Thus, IC37
      values alone were not sufficient to predict in vivo toxicity. We report that the
      degree of cell kill at concentrations of drug that saturate the B4 antigen and
      murine 50% lethal dose values provide additional parameters that may be
      predictive of in vivo cytotoxicity. Furthermore, we performed detailed
      cytotoxicity studies of the ricin species containing two and three covalently
      attached ligands, respectively. In vitro cytotoxicity testing using these samples
      revealed that Anti-B4-bR made with blocked ricin containing two covalently
      attached ligands is capable of depleting five logs of target cells in an in vitro
      cytotoxicity assay, while Anti-B4-bR comprised of blocked ricin with three
      ligands can deplete only one log of cells. Log cell kill at antigen saturating
      concentration, murine 50% lethal dose and biochemical analysis of the composition
      of blocked ricin are therefore important considerations for establishing the
      potential efficacy and safety of Anti-B4-bR.

PMID- 1379122
TI  - Chondrocytic differentiation of peripheral neuroectodermal tumor cell line in
      nude mouse xenograft.
AB  - We have established a cell line (KU-SN) from a peripheral neuroectodermal tumor
      originating in the left scapula of a 4-year-old girl. The original tumor was
      immunoreactive with antibodies for neurofilament proteins, neuron-specific
      enolase, vimentin, S100 protein, and beta 2-microglobulin. Dense core granules,
      50-150 nm in diameter, were identified by electron microscopy. The cell line was
      established from tumor cells in metastatic lung fluid. KU-SN cells were
      immunoreactive with the antibodies for neurofilament proteins, vimentin, neuron
      specific enolase, S100 protein, glial fibrillary acidic protein, cytokeratin, and
      carcinoembryonic antigen. Besides these neuronal features, KU-SN cells express
      type 2 collagen and insulin-like growth factor 1 receptor. The addition of
      insulin-like growth factor 1 (100 ng/ml) increased the growth rate of KU-SN cells
      2.1-fold over control. Some cells were positive for Alcian blue and alkaline
      phosphatase staining. Cytogenetic analysis of KU-SN cells disclosed a reciprocal
      chromosomal translocation [t(11,22)]. Northern blot analysis of KU-SN cells
      demonstrated amplified expression of the c-myc gene but not the N-myc gene. When
      tumor cells were transplanted into nude mice, cartilage was formed. The cartilage
      was immunoreactive with the antibody for HLA-ABC, indicating that it was derived
      from the tumor cells, not from mouse tissue. Chondrocytic differentiation was not
      observed in xenografts of Ewing's sarcoma cell lines SK-ES or RD-ES or the
      peripheral neuroectodermal tumor cell line SK-N-MC. These results indicate that
      KU-SN cells represent primitive neural crest cells having the potential for
      chondrocytic differentiation.

PMID- 1379123
TI  - Squamous metaplasia of normal and carcinoma in situ of HPV 16-immortalized human
      endocervical cells.
AB  - The importance of cervical squamous metaplasia and human papillomavirus 16 (HPV
      16) infection for cervical carcinoma has been well established. Nearly 87% of the
      intraepithelial neoplasia of the cervix occur in the transformation zone, which
      is composed of squamous metaplastic cells with unclear origin. HPV DNA, mostly
      HPV 16, has been found in 90% of cervical carcinomas, but only limited
      experimental data are available to discern the role of HPV 16 in this tissue
      specific oncogenesis. We have initiated in vivo studies of cultured endocervical
      cells as an experimental model system for development of cervical neoplasia.
      Using a modified in vivo implantation system, cultured normal endocervical
      epithelial cells formed epithelium resembling squamous metaplasia, whereas those
      immortalized by HPV 16 developed into lesions resembling carcinoma in situ. In
      contrast, their ectocervical counterparts formed well differentiated stratified
      squamous epithelium and a lesion with mild dysplastic change, respectively. The
      HPV 16-immortalized cells showed in vivo cytokeratin expression patterns similar
      to their respective normal counterparts, confirming their different origins.
      Thus, this study provides direct experimental evidence for the transformation of
      simple epithelial cells of endocervical origin into stratified squamous
      metaplasia and indicates the differential susceptibility of endo- and
      ectocervical epithelial cells for conversion to cancer by HPV 16.

PMID- 1379124
TI  - Reversal of divergent differentiation by ras oncogene-mediated transformation.
AB  - In embryogenesis, ovarian surface epithelial cells and ovarian granulosa cells
      arise through divergent differentiation from a common mesenchymal precursor, the
      urogenital ridge. In the adult rat, ovarian surface epithelial cells are
      nonsteroidogenic and keratin positive, while ovarian granulosa cells are
      steroidogenic and keratin negative. In culture, Kirsten murine sarcoma virus
      transformed, tumorigenic ovarian surface epithelial cells continued to express
      keratin but also became steroidogenic. Transformed ovarian granulosa cells
      remained steroidogenic but also acquired keratins. Mesodermally derived cells
      from other sources did not show these differentiation-related changes in response
      to transformation. The results suggest that v-ras oncogenes may cause the
      reversion of adult, developmentally related cells to the phenotype of a common,
      multipotential precursor. They also demonstrate the capacity of v-ras to either
      induce or reduce the same differentiated characteristic, depending on the
      developmental history of the target cells.

PMID- 1379125
TI  - Haemodynamic sequelae of pulmonary fibrosis following intratracheal bleomycin in
      rats.
AB  - OBJECTIVE: Intratracheal instillation of bleomycin in rats has been extensively
      used as an animal model of pulmonary fibrosis in humans, although it produces a
      patchy, airway based response. We proposed that the haemodynamic sequelae of the
      bleomycin model might be less severe than those associated with more diffuse lung
      injury. METHODS: Pulmonary and systemic haemodynamic indices were examined in
      adult Sprague-Dawley rats (approximately 400 g, n = 10) both at rest and during
      submaximal exercise on a rodent treadmill, approximately 60 days after
      intratracheal bleomycin (6 units.kg-1), and the results compared to a control
      group (n = 6). RESULTS: Compared to controls, mean pulmonary artery pressure
      (PPA) was increased by intratracheal bleomycin (p = 0.02) both at rest [24.5 (SEM
      2.6) v 18.2(0.9) mm Hg] and during exercise [34.7(3.0) v 26.7(0.7) mm Hg]. PPA
      pulse product was also increased, with a similar trend in right ventricular work
      index, but cardiac index was not altered. Right ventricular hypertrophy was noted
      on necropsy examination. Consistent with pulmonary fibrosis, lung dry weight,
      total protein, and hydroxyproline were also raised, and these values correlated
      strongly with (mean) PPA at rest (r2 = 0.86, 0.81, 0.69, respectively) and during
      exercise (r2 = 0.81, 0.79, 0.65, respectively). Packed cell volume was increased
      by intratracheal bleomycin, at 49(1) v 45(1)%, p = 0.02. CaO2 tended to decrease
      with exercise in the bleomycin group, although this was not statistically
      significant, while systemic oxygen delivery and consumption were not altered.
      CONCLUSIONS: Pulmonary hypertension and right ventricular hypertrophy occur in
      this model of lung fibrosis, and correlate with the severity of fibrosis.
      However, these sequelae were less severe than those previously demonstrated in
      association with crotalaria ingestion. We suggest that the haemodynamic sequelae
      of the intratracheal bleomycin model are consistent with patchy, airway based
      fibrosis, but reflect less well the haemodynamic sequelae of more diffuse
      fibrotic injury associated with systemic processes.

PMID- 1379127
TI  - In vitro differentiation of trout oligodendrocytes: evidence for an A2B5-positive
      origin.
AB  - The molecular differentiation of oligodendrocytes derived from larval trout brain
      was studied in dissociated cell cultures using a range of cell type and stage
      specific antibodies. By double-labeling immunostaining using A2B5 antibodies in
      conjunction with antibodies against the myelin glycoproteins IP1 and IP2 evidence
      was obtained that oligodendrocytes of trout in vitro originate from A2B5+
      precursor cells, which in terms of morphology closely resemble 0-2A progenitors
      of the mammalian CNS. Most surprisingly these cells did not differentiate in
      vitro beyond the level of IP2 expression, which signifies the initial step of
      oligodendroglial development in vivo. Hence it appears that in trout
      oligodendrocytes the initiation of the developmental program is intrinsically
      regulated, whereas further maturation of the cells requires appropriate
      environmental stimulation.

PMID- 1379126
TI  - Reduction of chromium(VI) to chromium(V) by rat liver cytosolic and microsomal
      fractions: is DT-diaphorase involved?
AB  - Incubation of rat liver cytosolic or microsomal fractions with chromium(VI) led
      to a dramatic decrease in chromium(VI) mutagenicity, as determined by the Ames
      Salmonella assay using the TA100 tester strain. The cytosol-dependent decrease in
      chromium(VI) mutagenicity was found to be counteracted in the presence of
      dicumarol, an inhibitor of the cytosolic enzyme NAD(P)H:quinone oxidoreductase
      (DT-diaphorase). In order to determine whether DT-diaphorase is a significant
      factor in enzymatic reduction of chromium(VI) in rat liver tissue, cytosolic and
      microsomal fractions were analyzed for NAD(P)H-dependent chromium (VI) reductase
      activity leading to chromium(V) formation by using electron paramagnetic
      resonance (EPR) spectroscopy. Reaction of chromium(VI) with NADH or NADPH in the
      presence of either cytosolic or microsomal fractions led to the formation of
      stable chromium(V)--NAD(P)H complexes. When glucose 6-phosphate (G6P) was present
      in the reaction as part of a NADPH-generating system, stable chromium(V)--G6P
      complexes were formed in addition to the chromium(V)--NAD(P)H complexes. The
      chromium(V) complexes had g values of 1.980-1.982 and superhyperfine splitting
      constants of 0.8-0.9 characteristic of bis(diol)oxochromium(V) complexes.
      Inhibition of 90% of the cytosolic DT-diaphorase activity by dicumarol led to
      only partial (20-22%) inhibition of chromium(V) formation. Visible and EPR
      spectroscopic studies showed that purified DT-diaphorase had no detectable
      chromium(VI) reductase activity and did not catalyze formation of chromium(V).
      Inhibition of 69% of microsomal aryl hydrocarbon hydroxylase activity by
      ketoconazole led to partial (10%) inhibition of chromium(V) formation. These
      results indicate that intracellular NAD(P)H-dependent enzymatic reduction of
      chromium(VI) in rat liver cannot be attributed to the activity of any one enzyme
      in the cytosolic or microsomal fractions. DT-diaphorase appears to play an
      indirect role in decreasing chromium(VI)-induced mutagenicity in Salmonella,
      possibly through interaction with other redox active cellular components. The
      involvement of diols such as sugars and pyridine nucleotides in stabilizing
      intracellularly generated chromium(V) is discussed.

PMID- 1379128
TI  - The neonatal rabbit brain glucose transporter.
AB  - The Glut 1 (Hep G2/rat brain) isoform of glucose transporter is expressed in
      significant amounts in adult mammalian brain. The purpose of our present study
      was to determine the brain cellular localization of Glut 1 during the late
      newborn stage of development, when brain cellular proliferation and
      differentiation is highly active. Employing immunohistochemistry and in-situ
      hybridization in 10-day-old neonatal rabbit brain sections, we undertook cellular
      localization of Glut 1 expression. Glut 1 protein and mRNA were mainly noted in
      considerable amounts within the 10-day-old brain microvasculature. Lower
      concentrations of Glut 1 immunoreactivity were present in certain glial cells
      found within the deeper cortical layers of brain. Northern blot analysis of total
      RNA from isolated microvasculature-enriched preparation, isolated and cultured
      neuronal and glial cells, whole brain and whole brain with the exclusion of
      microvasculature obtained from the 10-day-old, revealed the universal presence of
      a approximately 2.8 kb Glut 1 mRNA with the exception of the neuron-enriched
      cultures. We conclude that during the neonatal period, when parenchymal cellular
      proliferation is at a peak, Glut 1 is localized not only to the microvasculature
      but also to certain cells which express glial morphological characteristics. The
      neuronal cells either do not express Glut 1 or express minute amounts.

PMID- 1379129
TI  - Amniotic fluid granulocyte colony-stimulating factor in preterm and term labor.

PMID- 1379130
TI  - The spectrum of action of new immunosuppressive drugs.

PMID- 1379132
TI  - Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas
      derived from rheumatoid synovial tissue.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily
      affects synovial joints. Activated B lymphocytes and plasma cells are present in
      the synovial tissue and are thought to contribute to the immunopathology of the
      rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have
      generated B cell hybridomas from synovial tissue of an RA patient. Here we
      describe the immunoglobulin VH gene repertoire of eight IgM- and 10 IgG-secreting
      synovial-derived hybridomas. The VH4 gene family is highly represented (38.5%) in
      this panel of hybridomas compared with the frequency of VH4 gene expression in
      circulating B lymphocytes reported previously (19-22%) and with the VH4 gene
      frequency we observed in a panel of hybridomas derived in the same manner from
      the spleen and tonsil of normal individuals (19%). The increased frequency of VH4
      gene expression was not due to the expansion of a single B cell clone in vivo as
      none of these hybridomas was clonally related. Two synovial-derived hybridomas
      secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and
      the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins
      and cardiolipin. The antibodies secreted by the remaining synovial-derived
      hybridomas were not reactive with the autoantigens tested. The VH gene usage in a
      proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen
      provided preliminary evidence that CD5+ B cells in RA synovium have a similar
      increase of VH4 gene expression reported for CD5+ B cells from normal individuals
      and patients with chronic lymphocytic leukaemia.

PMID- 1379133
TI  - Anti-myeloperoxidase autoantibodies react with native but not denatured
      myeloperoxidase.
AB  - We wondered whether anti-myeloperoxidase (MPO) autoantibodies (MPO-ANCA) found in
      patients with systemic vasculitis react with a conformational epitope or epitopes
      on the MPO molecule. Sera from 15 human MPO-ANCA, and a polyclonal and a
      monoclonal anti-MPO antibodies were reacted with MPO in native and denatured
      states. Human MPO-ANCA and mouse monoclonal anti-MPO reacted with native MPO, and
      a 120-kD band representing the MPO hologenzyme, but not with denatured MPO
      fragments; however, MPO-ANCA and mouse anti-MPO did not demonstrate competitive
      inhibition of binding to MPO. Polyclonal rabbit anti-MPO reacted with both native
      and denatured MPO. All MPO-ANCA tested showed the same patterns of reactivity
      with native and denatured MPO in dot blot and Western blot analyses. Both
      polyclonal and monoclonal anti-MPO antibodies inhibited MPO's protein iodination
      by over 90%, whereas MPO-ANCA IgGs, normal IgGs and disease control IgGs did not.
      These data suggest that (i) MPO-ANCA interact with a conformational epitope on
      the MPO molecule; and (ii) MPO-ANCA from different patients have similar
      reactivity with native versus denatured MPO.

PMID- 1379131
TI  - IL-4 down-regulates the surface expression of CD5 on B cells and inhibits
      spontaneous immunoglobulin and IgM-rheumatoid factor production in patients with
      rheumatoid arthritis.
AB  - There is evidence to suggest that CD5+ B cells may be associated with
      autoimmunity, e.g. they are increased in patients with rheumatoid arthritis (RA).
      In this study, we found that the expression of CD5 on RA B cells increased
      spontaneously, following culture for up to 4 days in vitro in the absence of T
      cells, supporting the idea that the CD5+ B cell possesses distinctive features.
      The spontaneous increase of CD5 expression was down-regulated by recombinant IL-4
      (rIL-4). Other cytokines studied (rIL-1 alpha, rIL-2, rIL-5, rIL-6) did not alter
      CD5 expression. Studies of antibody production showed that rIL-4 could reduce
      spontaneous production of total IgG and IgM in non-stimulated RA T plus B cell
      cultures. Spontaneous production of IgM rheumatoid factor (IgM-RF), measured by a
      newly developed avidin-biotin complex ELISA, was also reduced by rIL-4.
      Furthermore, rIL-4 reduced the increase in IgM-RF production observed on
      stimulation with Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM).
      Thus, IL-4 might act as a regulator of the development of abnormal B cell
      differentiation in patients with RA.

PMID- 1379134
TI  - Human MoAbs produced from normal, HIV-1-negative donors and specific for
      glycoprotein gp120 of the HIV-1 envelope.
AB  - Human MoAbs of IgM class were developed against three regions of the HIV-1
      envelope. Uninfected donor lymphocytes were immunized in vitro with recombinant
      protein pB1. Four out of five antibodies were directed to different parts of the
      V3 region, which contains a major neutralizing site. Two out of these antibodies
      were directed to more than one amino acid sequence, indicating reactivity to
      discontinuous sites. Two of the human MoAbs inhibited viral spread between cells
      in tissue culture, interpreted as reactivities to conserved amino acid sequences
      exposed during viral maturation. No MoAb neutralized virus, which may be
      explained by the relatively low avidity of the antibodies. One MoAb was directed
      to a region containing amino acids participating in CD4 binding. This technique
      appears to allow formation of antibodies with fine specificities other than those
      obtained in infected hosts.

PMID- 1379136
TI  - [Observations on viral hepatitis in community medicine].

PMID- 1379135
TI  - Distending the uterus: what medium is best?
AB  - Because most diagnostic hysteroscopes take only a few minutes, the experienced
      hysteroscopist generally prefers to use CO2 distention. For extensive operative
      procedures, especially submucous myomectomy, glycine or sorbitol usually are
      chosen.

PMID- 1379137
TI  - Filgrastim.

PMID- 1379138
TI  - Stem cell-stromal cell interactions.

PMID- 1379139
TI  - Stroma-dependent hematolymphopoietic stem cells.

PMID- 1379140
TI  - [Reverse transcriptase from rat brain].

PMID- 1379141
TI  - Effects of cold treatment and ketosis induced by starvation on interferon
      production in leukocytes of lactating cows.
AB  - The production of interferons in blood and milk leukocytes of three groups of
      cows was measured to determine the effect of 6-days cold treatment (-2 degrees to
      -8 degrees C) and/or starving. The first group (cold) was treated with low
      ambient temperature (-2 degrees C to -8 degrees C) 11 hours every day for 6 days,
      the second (cold and starved) was treated with low temperature and starved for 6
      days. The third group (controls) was fed normally and kept in a barn at room
      temperature (18 degrees to 20 degrees C). The leukocytes of the control and the
      cold treated cows responded normally to interferon induction with Newcastle
      Disease Virus (NDV) and mitogens: phytohemagglutinin (PHA) and concanavalin A
      (ConA). The cows treated with low temperature and starved for 6 days developed
      biochemical blood changes of ketosis. Leukocytes of these cows with ketosis
      produced less interferon (p less than 0.05) than before starvation and less than
      leukocytes of the control cows and the cold treated cows. It can be assumed that
      ketosis caused by starving decreases the ability of a cow's leukocytes to produce
      interferons.

PMID- 1379142
TI  - Differential co-expression of long and short form type IX collagen transcripts
      during avian limb chondrogenesis in ovo.
AB  - Using RNA blot analysis of developmentally staged avian limb buds, we demonstrate
      that transcripts of several cartilage marker genes appear in limb tissue prior to
      overt chondrogenesis. Type II collagen mRNA, cartilage proteoglycan core protein
      mRNA, alpha 2(IX) collagen mRNA, and transcripts of the short form alpha 1(IX)
      collagen chain derived from the downstream promoter are co-expressed in limb
      tissue approximately 24-36 hours before the appearance of the respective
      polypeptides in differentiating cartilagenous tissue. Transcripts of the long
      form alpha 1(IX) collagen chain derived from the upstream promoter appear
      somewhat later in development; nearly coincident with the immunolocalization of
      type IX collagen in the cartilage elements of the limb. The spatial distribution
      of type II and type IX collagen transcripts was analyzed by in situ
      hybridization. Type II collagen and the long form alpha 1(IX) collagen
      transcripts co-localized in the chondrogenic elements of the developing forelimb.
      In contrast, short form alpha 1(IX) collagen transcripts which lack the 5' region
      encoding the NC4 globular amino-terminal domain were distributed throughout the
      non-chondrogenic, non-myogenic mesenchymal regions of the limb and were not
      detectable above background levels in the limb chondrogenic elements. The
      precocious appearance of several cartilage marker gene transcripts prior to
      chondrogenesis suggests that multiple levels of gene regulation including
      alternative promoter use, alternative RNA splicing, alternative polyadenylation,
      and other post-transcriptional as well as translational mechanisms are active
      prior to, and during avian limb chondrogenesis.

PMID- 1379143
TI  - Infectious disease therapy in the 1990s. Where are we heading?

PMID- 1379146
TI  - Superficial fungal infections of the skin. Diagnosis and current treatment
      recommendations.
AB  - Superficial fungal infections are common. Most diagnoses of fungal infections of
      the skin can be made by physical examination, assisted by the use of a Wood's
      lamp, skin scrapings for microscopic examination, and fungal cultures.
      Dermatophyte infections are common at all ages, in both sexes, and they have a
      worldwide distribution. These infections include tinea capitis, tinea cruris,
      tinea pedis, tinea corporis, tinea manuum and tinea barbae. Tinea versicolor,
      caused by Malassezia furfur, and candidal infections are also common. Treatment
      modalities include oral and topical agents. Good personal hygiene is an important
      adjunct to antifungal therapy. Decisions regarding the appropriateness of therapy
      in a given patient must take into account the extent and location of the
      infection, the benefits and risks of each of the treatments, and cost. Oral
      therapies include griseofulvin, ketoconazole, and itraconazole. There are a large
      variety of topical treatments, including nystatin, selenium sulfide, tolnaftate,
      haloprogin, miconazole, clotrimazole, and sodium thiosulfate. Important to
      successful treatment is compliance with what is sometimes a long course of
      treatment, and good personal hygiene.

PMID- 1379144
TI  - Angiotensin converting enzyme inhibitors versus digoxin for the treatment of
      congestive heart failure.
AB  - Angiotensin converting enzyme (ACE) inhibition and digoxin may be used in the
      management of heart failure. Digoxin increases myocardial contractility in vitro,
      and has a modest but durable beneficial effect in congestive heart failure due to
      impaired left ventricular systolic function. ACE inhibitors have clear beneficial
      effects in all grades of heart failure and, in addition, modify the natural
      history and reduce mortality. Comparative studies in mild to moderate heart
      failure reveal a tendency towards greater benefits and tolerability of ACE
      inhibitors over digoxin. ACE inhibition is indicated, in conjunction with
      diuretic therapy, for all grades of heart failure. Digoxin is best reserved for
      patients with atrial fibrillation and a rapid ventricular response, and for those
      whose heart failure is not controlled with an ACE inhibitor plus a diuretic. In
      patients with heart failure following myocardial infarction, digoxin is of modest
      benefit. Digoxin should be administered slowly and carefully to avoid acute
      vasoconstriction and toxicity. Provisional data suggest ACE inhibitors are also
      beneficial in these patients. However, the results of clinical trials presently
      in progress are required to clarify their role following myocardial infarction.

PMID- 1379145
TI  - Drug treatment of tuberculosis--1992.
AB  - The impact of the acquired immunodeficiency syndrome (AIDS) pandemic has made
      tuberculosis an increasing worldwide problem, and the effectiveness of modern
      chemotherapy has been blunted by the high incidence of primary drug resistance,
      especially in developing countries. The prospect of finding new and highly
      effective drugs similar to isoniazid or rifampicin is dim, yet the maximum
      benefits from the existing drugs which are highly effective have not been
      received. A 6-month regimen of isoniazid plus rifampicin, supplemented by
      pyrazinamide during the first 2 months, for treatment of uncomplicated
      tuberculosis is highly effective and the regimen of choice. Ethambutol should be
      added if the risk of isoniazid resistance is increased. A regimen of isoniazid,
      rifampicin, pyrazinamide and streptomycin for 4 months provides effective defence
      against smear-negative pulmonary tuberculosis. Re-treatment of multiple drug
      resistant tuberculosis remains a difficult therapeutic problem. At least 3 drugs
      that the patient has never previously received, and that are effective according
      to laboratory susceptibility testing, must be used. Preventive therapy against
      tuberculosis is accomplished with isoniazid for 6 to 12 months, although
      rifampicin plus isoniazid for 3 months has been used in the United Kingdom with
      success. In a mouse model, rifampicin plus pyrazinamide for 2 months is more
      effective than isoniazid for 6 months as preventive treatment. Patient
      noncompliance with medication remains the biggest problem in tuberculosis
      control, and is a complex issue. It can only be resolved by multiple approaches.
      Intermittent directly observed short course chemotherapy is a major, but not the
      only, possible solution.

PMID- 1379147
TI  - Current recommendations for the treatment of Lyme disease.
AB  - Lyme disease is a multisystem inflammatory disease caused by infection with
      Borrelia burgdorferi. Soon after the tick bite which transmits the infection, the
      pathognomonic skin rash erythema chronicum migrans occurs in 50 to 70% of
      patients, often with associated symptoms resembling a 'summer cold' or viral
      infection. Therapy for this stage of disease consists of 3 to 4 weeks of oral
      therapy. The agents currently used are: amoxicillin (500 mg 3 or 4 times daily)
      with or without probenecid 500 mg 3 times daily, doxycycline (100 mg twice
      daily), or tetracycline (500 mg 4 times daily). Longer duration therapy has never
      been evaluated and therefore is not currently indicated. Even patients with
      severe early manifestations of Lyme disease should be treated orally. Later
      features of Lyme disease include carditis and neurological disease, which can
      occur days to approximately 9 months after the onset of illness, and arthritis
      and neurological disease which can occur weeks to years after the onset of the
      illness. Treatment at this stage is with 2 to 3 weeks of intravenous antibiotics,
      currently cefotaxime (3 g every 12 hours), ceftriaxone (1 g every 12 hours or 2 g
      every day) and benzylpenicillin (14 g in divided doses). There is no evidence
      that longer duration therapy is indicated or more efficacious. The exception to
      this suggestion is the patient with isolated facial seventh cranial nerve palsy;
      if such a patient has no other signs or symptoms to suggest Lyme disease and has
      normal spinal fluid, oral therapy is usually sufficient, although some physicians
      will give concomitant corticosteroids to hasten the resolution of the palsy. Of
      major consequence to the practitioner and patient is the possibility that
      persistent symptoms (e.g. fibromyalgia) may be caused by a process which is no
      longer antibiotic-sensitive. Special care in the management of so-called 'chronic
      Lyme disease' is crucial lest the clinician prescribes prolonged or unending
      courses of antibiotics for such noninfectious problems.

PMID- 1379148
TI  - Treatment options for the pharmacological therapy of neonatal meningitis.
AB  - Neonatal bacterial meningitis has a relatively low incidence in developed
      countries, but continues to cause morbidity and mortality despite advances in
      antimicrobial therapy. Bacterial pathogens commonly associated with neonatal
      meningitis include Group B streptococci, Escherichia coli K1 and other coliforms,
      Listeria monocytogenes and staphylococci. As it can be difficult to differentiate
      meningitis from septicaemia in neonates, empirical antibiotic therapy should be
      effective for both. Selection of an empirical antibiotic regimen should be based
      on: (a) bacterial prevalence and susceptibility; (b) drug characteristics; (c)
      postnatal age at the onset of disease; and (d) patient-specific factors. A
      penicillin in combination with an aminoglycoside or cefotaxime is commonly used
      in empirical therapies. The increased risk of staphylococcal infection in older
      neonates requires consideration of an antistaphylococcal antibiotic in the
      empirical therapy regimen. Once a causative organism has been identified,
      antimicrobial therapy should be directed towards that pathogen. Duration of
      therapy remains empirical, but should be at least 7 days for documented bacterial
      meningitis. Viral meningitis continues to have a high mortality despite the
      availability of antiviral agents. Adjunctive therapies may further reduce the
      morbidity and mortality of meningitis. While most of these therapeutic options
      have not been investigated in neonates, they may prove to be of benefit in the
      future. Anti-inflammatory agents, such as glucocorticoids, nonsteroidal anti
      inflammatory agents and immunoglobulin, may modulate the inflammatory response of
      a meningeal infection. Other possible therapies in neonatal meningitis include
      cerebral blood flow modulators and disease prevention with maternal vaccines and
      perinatal antibiotics. Practical aspects of drug therapy such as route of
      administration and serum drug concentration monitoring can improve both drug
      therapy and patient outcome. While antibiotics have greatly improved the
      treatment outcome of neonatal meningitis, it is clear that additional
      intervention will be required to increase cure rates and reduce sequelae.

PMID- 1379149
TI  - Dexfenfluramine. A review of its pharmacological properties and therapeutic
      potential in obesity.
AB  - Dexfenfluramine stimulates serotoninergic activity by inhibiting serotonin
      reuptake into presynaptic neurons and by enhancing its release into brain
      synapses. Based on the serotonin hypothesis of appetite control these effects
      would be expected to reduce food intake and thus body-weight. Studies in animal
      models and severely overweight patients have confirmed the effectiveness of
      dexfenfluramine as a weight-reducing agent which appears to be well tolerated.
      Permanent weight loss is the goal of weight-reducing strategies and, based on
      current clinical evidence, dexfenfluramine appears to exert a weight reducing
      effect over periods of up to 12 months without development of tolerance, a
      problem that has limited the long term use of other pharmacological agents used
      in the treatment of this disorder. Dexfenfluramine facilitated weight loss in
      patients who had not responded satisfactorily to other weight-reducing
      strategies, prevented relapse in those patients who had achieved weight reduction
      by other methods, and corrected disturbed eating patterns (and therefore reduced
      weight gain) in small studies involving patients with premenstrual syndrome,
      seasonal affective disorder and nicotine withdrawal syndrome. Follow-up of the
      longest study reported with dexfenfluramine suggests that continued therapy is
      required in severely overweight patients if weight loss is to be maintained.
      Dexfenfluramine has not been directly compared with nonpharmacological measures
      of weight control such as behaviour modification or exercise programmes. The
      decision that pharmacological means are indicated in overweight patients must be
      highly individualised, and must consider the many complex factors that often
      contribute to overweight states, as well as the anticipated magnitude of drug
      effect. Despite such a cautionary note, and the expected need (at this stage of
      its development) for an expanded clinical study programme in certain areas,
      dexfenfluramine is a clear advance in the pharmacological approach to improved
      management of overweight individuals.

PMID- 1379151
TI  - Intranasal fluticasone propionate. A review of its pharmacodynamic and
      pharmacokinetic properties, and therapeutic potential in allergic rhinitis.
AB  - Fluticasone propionate is a potent topical anti-inflammatory corticosteroid with
      low systemic activity. Available pharmacodynamic data are only preliminary;
      however, large placebo- and drug-controlled clinical studies involving almost
      4000 patients with seasonal allergic rhinitis and 1500 with perennial allergic
      and nonallergic rhinitis have confirmed the efficacy of intranasal fluticasone
      propionate in the control of nasal symptoms. Fluticasone propionate generally
      demonstrated similar efficacy compared with intranasal beclomethasone
      dipropionate, flunisolide acetonide and oral astemizole and better or a trend
      towards better efficacy compared with oral loratadine, terfenadine, cetirizine
      and intranasal sodium cromoglycate (cromolyn sodium) against nasal symptoms. The
      incidence of adverse effects in association with intranasal fluticasone
      propionate appears to be comparable to that observed with placebo; the most
      frequently reported effects are nasal dryness/burning, epistaxis and headache.
      Consistent with its minimal systemic availability, intranasal fluticasone
      propionate in a dosage of up to 4 mg/day does not cause adrenal suppression.
      Thus, based on early data from large clinical trials, fluticasone propionate
      administered once daily offers an effective and convenient treatment option in
      patients with seasonal and perennial allergic rhinitis, and is distinguished by
      its low oral bioavailability.

PMID- 1379150
TI  - Cibenzoline. A review of its pharmacological properties and therapeutic potential
      in arrhythmias.
AB  - Cibenzoline is a class I antiarrhythmic drug with limited class III and IV
      activity which can be administered orally or intravenously. An elimination half
      life of about 8 to 12 hours permits twice daily administration, although age and
      renal function must be considered when determining dosage. Cibenzoline has some
      activity in ventricular and supraventricular arrhythmias, including drug
      refractory ventricular tachycardia or ventricular arrhythmias following recent
      acute myocardial infarction, although results in patients with sustained
      ventricular tachycardia are less promising. In comparative trials, cibenzoline
      has demonstrated efficacy similar to or better than that of a variety of other
      class I antiarrhythmic drugs and was at least as well tolerated, with a more
      convenient dosage schedule. However, further studies to clarify the proarrhythmic
      effects of cibenzoline and its use in patients with impaired left ventricular
      function are required, and the use of cibenzoline (and other class I
      antiarrhythmic agents) in patients with other than potentially lethal ventricular
      arrhythmias should be avoided following the results of the CAST studies. Thus,
      cibenzoline is an effective antiarrhythmic agent with a favourable
      pharmacokinetic profile that may be considered with other class I drugs in
      patients requiring therapy for high risk arrhythmias.

PMID- 1379153
TI  - Patient-controlled spinal opiate analgesia in terminal cancer. Has its time
      really arrived?

PMID- 1379152
TI  - Sumatriptan. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic efficacy in the acute treatment of migraine and cluster headache.
AB  - Sumatriptan is a serotonin1 (5-HT1) receptor agonist, which is effective in the
      acute treatment of migraine headache. Its antimigraine activity is believed to
      derive from selective vasoconstriction of cranial blood vessels which are dilated
      and distended during migraine headache and/or from inhibition of neurogenically
      mediated inflammation in the dura mater. In placebo-controlled comparative
      studies, sumatriptan reduced migraine headache from 'moderate or severe' to 'mild
      or none' within 2 hours in 50 to 73% of patients following oral administration of
      100 or 200 mg, and within 1 hour in 70 to 80% of patients following subcutaneous
      doses of 6 to 8 mg or intranasal doses 20 mg into each nostril. In addition,
      sumatriptan alleviated the accompanying symptoms of nausea, vomiting, and
      photophobia/phonophobia more effectively than placebo, and permitted higher
      percentages of patients to resume normal daily activities. Sumatriptan 100 mg
      orally was more effective in the acute treatment of migraine than oral
      combination therapy consisting of ergotamine 2 mg plus caffeine 200 mg or aspirin
      900 mg plus metoclopramide 10 mg. Pooled data from nearly 5000 patients treated
      with either oral or subcutaneous sumatriptan in clinical trials indicate that it
      is well tolerated. However, migraine recurrence within 24 or 48 hours of initial
      symptom resolution developed in approximately 40% of patients treated with
      sumatriptan, irrespective of route of administration. It is likely that migraine
      recurrence is related to the short half-life of the drug (approximately 2 hours).
      Future studies should attempt to ascertain whether additional doses of
      sumatriptan will help prevent migraine recurrence in patients with attacks of
      long duration and if so, should determine the optimum interval between dosages.
      In conclusion, sumatriptan is an important addition to the range of drugs
      currently available for acute treatment of migraine. It provides rapid relief
      from debilitating symptoms in a high percentage of patients, particularly after
      subcutaneous administration. At this stage in its development a number of
      questions remain to be answered - most notably whether repeat doses will help
      prevent recurrent attacks and which patients are most likely to respond to
      therapy. Nevertheless, sumatriptan presently offers a combination of efficacy and
      tolerability that is unique in this particular clinical setting.

PMID- 1379155
TI  - Appetite suppressants. A review.
AB  - Centrally acting appetite suppressant drugs used in the treatment of obesity fall
      into 2 broad pharmacological categories; those which act via brain catecholamine
      pathways and those which act via serotonin pathways. Of the former group,
      amphetamine and phenmetrazine are no longer recommended because of their
      stimulant properties and addictive potential. The remaining drugs in this class
      include amfepramone (diethylpropion), phentermine, mazindol and
      phenylpropanolamine. All have been shown to reduce appetite and lower food
      intake, thereby helping obese patients more easily keep to a low-calorie diet and
      lose weight. They all have some sympathomimetic and stimulant properties.
      Anorectic drugs which promote serotonin neurotransmission have no such stimulant
      or sympathomimetic properties. They are fenfluramine, together with its recently
      introduced dextrorotatory stereoisomer dexfenfluramine, and fluoxetine. They
      reduce appetite and food intake and are effective in the treatment of obesity.
      Anorectic drugs should be reserved for those who are clinically at risk from
      being overweight, and then only as part of a comprehensive weight-reducing
      programme including regular dietary counselling. Although current licensing
      regulations only allow their use over a relatively short period (12 to 16 weeks),
      clinical trials have shown them to be effective over longer periods, particularly
      in preventing weight regain. Of the compounds currently indicated for use in
      obesity, dexfenfluramine appears to have the most suitable pharmacological
      profile, although it should not be given to patients with a history of
      depression. When used appropriately, appetite suppressants can be of real
      therapeutic benefit, and pose little risk.

PMID- 1379154
TI  - Secondary hypertension. An overview of its causes and management.
AB  - Primarily hypervolaemic, high output forms of hypertension, with features
      indicating or strongly suggesting fluid overload as the cause of elevated cardiac
      output, resulting from renal disease with reduced glomerular filtration rate
      causing sodium retention, renal tubular causes of sodium retention, greatly
      excessive sodium intake and low renin hypertension, can be treated by reduction
      of sodium intake and potentiation of its excretion by diuretic therapy, removal
      of the cause (e.g. aldosteronoma), and calcium antagonists. Excessive
      vasoconstriction resulting from noradrenaline (norepinephrine) in neurogenic
      hypertension, phaeochromocytoma, orthostatic hypertension and alpha-adrenergic
      drug administration; angiotensin excess due to renal ischaemia brought about by
      aortic coarctation, renal arterial and arteriolar stenosis, intraluminal
      obstruction, external renal compression, renin-producing tumours, intrinsic
      kidney diseases and excessive renin substrate; and vascular structural disorders
      such as atherosclerosis, arteriolitides and fibrosis with or without
      calcification of major arteries may also induce hypertension. Secondary
      hypertension of uncertain mechanism may occur in hyperparathyroidism, hyper-or
      hypothyroidism, or acromegaly. All are best treated by appropriate correction of
      the endocrine excess or deficiency. It may also occur in pregnancy, where the
      mechanism may involve prostaglandin-thromboxane imbalance or calcium deficiency;
      calcium deficiency with some evidence of benefit from calcium supplements; and
      the recumbent hypertension paradoxically associated with autonomic failure.
      Excellent responses to specific correction of the underlying cause or
      pathogenetic mechanism is usual in young individuals but less frequent in older
      patients.

PMID- 1379156
TI  - The high-risk unstable angina patient. An approach to treatment.
AB  - Unstable angina, an intermediate stage in acute coronary ischaemic syndromes,
      accounts for about 50% of all admissions to the coronary care units in the United
      States today. It may progress to myocardial infarction in 15% of cases in the
      first 2 days, and the in-hospital mortality rate is 5%. The pathological hallmark
      of this syndrome, confirmed by angioscopy, is fissure of the atherosclerotic
      plaque within the coronary artery, leading to platelet adhesion and aggregation
      and fibrin-platelet thrombus formation, which may accelerate progression of the
      stenotic lesion. Management of unstable angina is aimed at ameliorating symptoms
      and reducing ischaemia, improving ventricular function, preventing recurrent
      ischaemia, myocardial infarction and death, and lastly, containing progression of
      the underlying coronary artery disease. Acute management includes bedrest,
      aspirin, heparin, nitroglycerin (glyceryl trinitrate) infusion and beta-blockers
      and calcium channel blockers in selected cases. After the patient is clinically
      stabilised, provocative tests and angiography may be performed, to be followed by
      angioplasty or bypass surgery, if necessary. In cases that are refractory to
      optimal medical therapy, interventions should be performed on a more emergent
      basis. Long term management includes aspirin and beta-blockers, if there is prior
      infarction, and control of the conventional risk factors.

PMID- 1379157
TI  - Pharmacological management of juvenile rheumatoid arthritis.
AB  - The goals of pharmacotherapy in juvenile rheumatoid arthritis (JRA) are to
      suppress chronic synovitis which causes potential cartilage destruction and
      deformities, to control the systemic effects of inflammation (including growth
      retardation and nutritional deficits), relieve pain and limit psychological
      impact of disease. Currently available methods include nonsteroidal anti
      inflammatory drugs (NSAIDs) such as aspirin, salicylates, naproxen, tolmetin,
      ibuprofen and indomethacin; disease modifying antirheumatic drugs (DMARDs) such
      as oral and injectable gold salts, hydroxychloroquine, penicillamine, oral and
      injectable methotrexate, and sulfasalazine; oral (daily or on alternate days),
      intravenous pulse or intra-articular corticosteroids; immunosuppresants,
      including cyclophosphamide, chlorambucil, cyclosporin, and azathioprine; and
      gammaglobulin and other experimental therapies. Over the past 10 years,
      rheumatologists have adopted more aggressive pharmacological treatment of JRA. As
      time progresses and the safety of certain drugs such as methotrexate and
      sulfasalazine becomes clearer, wider and earlier use of these agents can be
      expected. Still the approach to treatment is a 'step by step' one, starting with
      the classical NSAIDs and ending with the DMARDs as needed.

PMID- 1379158
TI  - Management of neonatal hyperbilirubinaemia and prevention of kernicterus.
AB  - Hyperbilirubinaemia remains one of the most common and more important
      pathological conditions in the newborn. The possibility that the so-called
      physiological or developmental hyperbilirubinaemia, with relatively low levels of
      serum bilirubin, could be responsible for bilirubin encephalopathy in the small
      premature infant is of great concern to the neonatologist; premature newborns are
      prone to developing hyperbilirubinaemia. Current methodologies for suppressing
      severe neonatal jaundice include: (a) attempts to stimulate liver conjugating
      enzymes using drugs such as phenobarbital; (b) attempts to degrade bilirubin with
      phototherapy; and (c) exchange transfusion. It is too soon to consider tin
      protoporphyrin as a drug for the prevention and treatment of neonatal
      hyperbilirubinaemia. However, if it can be shown that tin-protoporphyrin can
      serve as a safe and less costly alternate treatment, a considerable improvement
      in the management of neonatal jaundice would be achieved.

PMID- 1379159
TI  - Oxcarbazepine. A review of its pharmacology and therapeutic potential in
      epilepsy, trigeminal neuralgia and affective disorders.
AB  - Oxcarbazepine is the 10-keto analogue of carbamazepine but has a distinct
      pharmacokinetic profile. In contrast to the oxidative metabolism of
      carbamazepine, oxcarbazepine is rapidly reduced to its active metabolite, 10,11
      dihydro-10-hydroxy-carbamazepine. With the possible exception of the P450IIIA
      isozyme of the cytochrome P450 family, neither oxcarbazepine nor its monohydroxy
      derivative induce hepatic oxidative metabolism. Direct comparison of
      oxcarbazepine and carbamazepine has shown no difference in efficacy between these
      2 agents in terms of reducing seizure frequency in patients with partial epilepsy
      with or without secondary generalisation, or with tonic-clonic seizures.
      Substitution of oxcarbazepine for carbamazepine in multiple antiepileptic drug
      regimens improved seizure control in some patients with refractory epilepsy;
      however, the rise in serum concentrations of concurrent antiepileptic agents
      secondary to elimination of carbamazepine-associated hepatic enzyme induction may
      have also played a role. Substitution of oxcarbazepine for carbamazepine was
      associated with improved cognition and alertness in some patients with epilepsy.
      Limited data indicate that oxcarbazepine may be a useful alternative to
      carbamazepine in the management of trigeminal neuralgia. Experience in patients
      with acute mania is promising, but the value of oxcarbazepine in managing
      affective disorders, particularly as a prophylactic agent, is not established.
      Oxcarbazepine may be better tolerated than carbamazepine; however, the current
      published database is small and the potential for oxcarbazepine to induce the
      type of serious idiosyncratic reactions occasionally associated with
      carbamazepine is unknown. Hyponatraemia has been reported in patients treated
      with oxcarbazepine. Although apparently asymptomatic, fluid restriction may be
      deemed necessary in some patients to reduce the risk of precipitating seizures
      secondary to low serum sodium. Thus, oxcarbazepine appears to be an effective
      substitute for carbamazepine in those patients intolerant of this agent, or
      experiencing significant drug interactions. Wider clinical experience should help
      clarify the long term efficacy and tolerability of oxcarbazepine. Pharmacokinetic
      advantages over current antiepileptic drugs, carbamazepine in particular, may
      then favour oxcarbazepine for consideration as a first-line agent in the
      management of partial and tonic-clonic epilepsy.

PMID- 1379161
TI  - Insulin and insulin-like growth factors (IGFs) stimulate production of IGF
      binding proteins by ovarian granulosa cells.
AB  - Ligand blot analysis of granulosa cell (GC)-conditioned culture medium revealed
      several easily measurable insulin-like growth factor (IGF)-binding proteins
      (IGFBPs), including IGFBP-3 [40-44 kilodaltons (kDa)] and IGFBP-2 (34 kDa). In
      the present study, IGF-I, in a dose-dependent manner, significantly stimulated
      the production of these IGFBPs. Insulin, but not IGF-II, mimicked IGF-I's action
      on IGFBP-3 and -2 production, but was less potent. The synthetic IGF, long R3-IGF
      I, which has very low affinity for IGFBPs and only slightly reduced affinity for
      the IGF-I (type I) receptor, had significantly greater potency in stimulating
      IGFBP-3 and -2 production compared to IGF-I. Des-(1-3)-IGF-I had similar effects.
      IGF-I, IGF-II, and the IGF-I analogs, but not insulin, also induced production of
      an unidentified 30-kDa IGFBP not normally detectable in these cultures. However,
      in the presence of epidermal growth factor (which was without independent effect
      on the 30-kDa IGFBP), insulin also induced this 30-kDa IGFBP. By Northern
      analysis the expression of IGFBP-3 mRNA was found to be significantly stimulated
      by IGF-I. In summary, insulin stimulated IGFBP-3 and -2 production in a manner
      that mimics that of IGF-I and the more potent long R3-IGF-I. However, its low
      potency suggested that IGFBP production is regulated via the IGF-I (type I)
      receptor. The much higher potency of long R3-IGF-I compared to that of IGF-I
      suggests that the IGFBPs themselves modulate the action of IGFs by sequestering
      exogenous IGFs. Thus, one cellular response to IGF stimulation is the production
      of IGFBPs, which, in turn, reduce or negate the biological activity of the IGFs.
      The effects of insulin-like peptides are exerted at least in part by increasing
      levels of mRNA for specific BPs.

PMID- 1379162
TI  - Regulation of insulin-like growth factor binding protein-3 messenger ribonucleic
      acid expression by insulin-like growth factor I.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is an important modulator
      of the anabolic and mitogenic actions of the insulin-like growth factor (IGF)
      peptides. Previous studies have shown that the IGFs themselves can elevate levels
      of IGFBP-3 in vivo and in vitro. However, the regulatory mechanisms responsible
      for IGF-induced increases in IGFBP-3 are unclear. In this study we examined the
      expression of messenger RNA (mRNA) encoding IGFBP-3 in cultured bovine and human
      fibroblasts, two cell lines that secrete IGFBP-3 under IGF-I control. Northern
      analysis of bovine fibroblast RNA hybridized with a specific bovine IGFBP-3
      complementary DNA probe indicated a single 2.8-kilobase (kb) transcript readily
      detectable within 2 h in IGF-I- or insulin-treated, but not in untreated, cells.
      IGFBP-3 mRNA abundance was maximal around 6 h, and remained elevated after 24 h
      of treatment. Secreted IGFBP-3 protein appeared more slowly. By Western ligand
      blotting, IGFBP-3 was not detected in medium from bovine fibroblasts incubated
      with IGF-I for 2, 4, or 6h, but was apparent after 24 h IGF-I treatment.
      Induction of IGFBP-3 mRNA was blocked when RNA synthesis was inhibited by
      actinomycin D. Furthermore, IGFBP-3 mRNA and protein was induced by different IGF
      I analogs in direct relation to the ability of the peptides to bind to the type I
      IGF receptor, indicating a receptor-mediated process. GH had no effect on IGFBP-3
      mRNA or protein levels in these cells. In contrast to its effect in bovine
      fibroblasts, IGF-I had no significant effect on steady state levels of IGFBP-3
      mRNA in cultured human fibroblasts. A human IGFBP-3 complementary DNA probe
      hybridized to a single 2.8-kilobase mRNA species abundant in normal and SV40
      transformed human fibroblasts under all culture conditions, and IGFBP-3 protein
      was secreted by these cells in the absence of exogenous stimuli. In human
      fibroblast cultures, IGF-I rapidly increased levels of IGFBP-3 in the medium
      without influencing transcript levels. Steady state levels of induced or
      constitutively expressed IGFBP-3 mRNA did not change significantly after 6h in
      the presence of actinomycin D, even though general RNA synthesis was inhibited
      more than 98%. These data demonstrate that expression of mRNA encoding IGFBP-3 is
      differentially controlled by IGF-I in bovine and human fibroblasts. Whereas
      cultured human fibroblasts may be suitable to study posttranscriptional
      regulation of IGFBP-3 availability, cultured bovine fibroblasts may provide a
      useful model system to probe the molecular mechanisms of IGFBP-3 gene expression
      and regulation by IGF-I.

PMID- 1379163
TI  - Effect of in vivo administration of recombinant acidic fibroblast growth factor
      on thyroid function in the rat: induction of colloid goiter.
AB  - We have recently demonstrated that the iv administration of 0.6-60
      micrograms/kg.day of acidic fibroblast growth factor (acidic FGF) increases
      thyroid weight in male and female rats. Interestingly, measurement of serum TSH
      and thyroid hormones in rats treated with 6 micrograms/kg.day acidic FGF for 30
      days revealed only a slight increase in serum T4 and reverse T3 concentrations.
      Since thyroid function was only examined 24 h after the 30th daily treatment, we
      performed a series of experiments to evaluate the effects of acidic FGF on
      thyroid function following single and 6 multiple injections of acidic FGF. There
      was a small increase in the serum TSH concentrations at 2, 4, 8, and 24 h after a
      single high dose iv injection of acidic FGF (60 micrograms/kg). In contrast,
      serum T3 concentrations were slightly decreased at 2, 4, and 8 h after acidic FGF
      administration. There was no effect of a single injection of acidic FGF on serum
      T4, reverse T3, or thyroglobulin concentrations. After 6 days of treatment, there
      was a 34% increase in the thyroid weights of rats treated with acidic FGF.
      Analysis of serum hormones revealed a slight increase in serum TSH, T3, and T4
      concentrations in acidic FGF-treated rats, but no change in serum reverse T3 or
      thyroglobulin concentrations. There was no effect of acidic FGF administration on
      thyroid radioiodine uptake, the intrathyroidal metabolism of radioiodine, or the
      relative amounts of thyroidal thyroglobulin or peroxidase messenger RNAs, or on
      liver 5'-deiodinase activity. In hypophysectomized rats, with no detectable
      levels of serum TSH, acidic FGF failed to increase thyroid weight. These data
      suggest that FGFs may participate with TSH in the regulation of thyroid weight
      and colloid accumulation, and that autocrine or paracrine growth factors may be
      involved in the pathogenesis of colloid goiter.

PMID- 1379160
TI  - Iloprost. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic potential in peripheral vascular disease, myocardial ischaemia and
      extracorporeal circulation procedures.
AB  - Iloprost is an analogue of epoprostenol (prostacyclin; PGI2; a potent but short
      lived prostanoid mainly produced in the vascular endothelium) and mimics the
      pharmacodynamic properties of this compound, namely: inhibition of platelet
      aggregation, vasodilatation and, as yet ill-defined, cytoprotection. Improved
      metabolic and, in particular, chemical stability enhance the clinical utility of
      iloprost. When administered as an intermittent intravenous infusion at less than
      or equal to 2 ng/kg/min for 2 to 4 weeks, iloprost reduced rest pain and improved
      ulcer healing in 40 to 60% of patients with critical leg ischaemia, including
      diabetic patients, and delayed amputation in the majority of responding
      individuals. Similar benefits have been seen in thromboangiitis obliterans and,
      in patients with severe Raynaud's phenomenon, shorter courses of therapy reduced
      the frequency, intensity and duration of ischaemic episodes for at least 6 weeks.
      The very few comparative trials reported to date (i.e. vs nifedipine in Raynaud's
      phenomenon; vs low-dose aspirin in thromboangiitis obliterans) have favoured
      iloprost, but comparisons with more established agents are needed to assess this
      drug's value in less severe forms of peripheral ischaemia, such as intermittent
      claudication. At present, iloprost is administered intravenously and this is a
      limitation to treatment. The potent, rapidly reversible antiplatelet activity of
      iloprost suits it for use in extracorporeal circulation and for the
      intraoperative management of heparin-induced platelet activation. Although
      results in animal models of ischaemic myocardial injury are encouraging,
      preliminary clinical experience in patients with myocardial ischaemia or
      infarction has been disappointing. Most patients tolerate iloprost infusion rates
      of up to 2 ng/kg/min. Headache and flushing are extremely common and are the
      suggested end-point of dose titration, as higher doses are associated with a
      significant incidence of gastrointestinal distress and, ultimately, hypotension.
      Thus, iloprost provides a pharmacotherapeutic option for patients with severe
      peripheral vascular disease, a condition for which few alternative drug therapies
      exist. Its potent but short-lived effects make it well-suited to certain
      therapeutic niches such as the management of intraoperative platelet activation.
      Prostanoid analogues have far-reaching therapeutic potential and further
      experience with iloprost will no doubt help to define its clinical applications.

PMID- 1379164
TI  - Cyclic adenosine 3',5'-monophosphate increases beta-adrenergic receptor
      concentration in cultured human fetal lung explants and type II cells.
AB  - cAMP regulates the maturation of many biochemical processes that occur during
      normal lung development, including the changing levels of surfactant proteins and
      phospholipids. We examined the effect of cAMP on the beta-adrenergic receptor
      concentration in the developing human lung. Isobutylmethylxanthine, a cAMP
      phosphodiesterase inhibitor, increased both the tissue cAMP content and beta
      adrenergic receptor concentration in treated explants above those in untreated
      explants. 8-Bromo-cAMP treatment also elevated the beta-adrenergic receptor
      concentration of lung explants compared to that in untreated controls. These data
      indicate the ability of elevated cAMP to increase the beta-adrenergic receptor
      concentration. Both lung cAMP and beta-adrenergic receptor concentrations
      increase spontaneously in culture. To test for a possible causal relationship, we
      cultured explants with protein kinase inhibitors. We found that H-8, a
      preferential inhibitor of the cAMP-dependent protein kinase [protein kinase-A
      (PKA)], but not H-7, which inhibits PKA and protein kinase-C with similar
      potency, blocked the spontaneous rise in beta-adrenergic receptor concentration
      in human fetal lung explants, indicating that PKA activity is required for this
      rise in beta-adrenergic receptor concentration. Type II cells isolated from
      cultured lung treated with H-8 had fewer beta-adrenergic receptors than cells
      isolated from untreated explants. These studies show that cAMP increases the beta
      adrenergic receptor concentration in human fetal lung and specifically in type II
      cells through a PKA-dependent mechanism, consistent with a role for cAMP in beta
      adrenergic receptor regulation during normal lung development.

PMID- 1379165
TI  - Substance P stimulates luteinizing hormone secretion from anterior pituitary
      cells in culture.
AB  - Substance P (SP) is present in the anterior pituitary gland (AP), and its
      concentration there is regulated by the hormonal status of the animal. The
      observation that SP is releasable from hemipituitaries in a K(+)-stimulated,
      Ca(2+)-dependent manner and the demonstration of SP-binding sites in the AP have
      led to the suggestion that SP participates in a paracrine or autocrine manner in
      the regulation of AP function. Contradictory reports of the effects of SP on the
      secretion of AP hormones, particularly LH, led us to address the question of
      whether SP can act directly on the AP to effect LH secretion. We found that SP
      (100 nM) can stimulate LH release (300-400% of control values) in short term
      cultures of AP cells and that this effect varies as a function of the age and sex
      of the animal. There was no significant effect of SP on the release of LH from AP
      cells of male and female prepubertal rats (20-30 days). During the peripubertal
      period (30-35 days), a sharp increase in the response to SP occurred in both
      sexes. This responsiveness was dose dependent and persisted at all ages studied
      in AP cells from the female rat. In contrast, the responsiveness of AP cells from
      male rats that developed during the peripubertal period diminished during
      maturation and was absent after 60 days of age. When adult female rats were
      exposed to androgens for 6 weeks in vivo and tested for the ability of SP to
      stimulate the LH secretion, the response was significantly diminished. These
      studies support the speculation that SP has a functional role in the secretion of
      LH.

PMID- 1379167
TI  - Steroidogenic enzyme expression in porcine conceptuses during and after
      elongation.
AB  - The following studies were performed to investigate levels of expression of
      steroidogenic enzymes in porcine conceptuses between days 12 and 21 postmating
      and to correlate these findings with estrogen levels in conceptus tissues. In the
      first experiment, levels of steroidogenic enzymes in individual day 12
      blastocysts were examined by Western immunoblot analyses. In a second experiment,
      Northern blot, slot blot, and Western immunoblot analyses for 17 alpha
      hydroxylase cytochrome P450 (P450(17) alpha) were performed on conceptus tissue
      pooled for each uterine horn of sows on days 12, 14, 16, and 21 postmating. On
      day 12, P450(17) alpha) protein was detectable in 6-mm blastocysts, with highest
      levels apparent in 10- to 15-mm (tubular) blastocysts. Filamentous blastocysts
      appeared to have less P450(17) alpha) protein than did littermate tubular
      blastocysts. Side-chain cleavage cytochrome P450 (P450scc) and aromatase
      cytochrome P450 (P450arom) followed a pattern similar to that of P450(17) alpha.
      3 beta-Hydroxysteroid dehydrogenase was undetectable by Western analysis in
      blastocysts at the stages examined, but was detectable in placenta from fetuses
      at later stages of gestation. In pooled tissue, P450(17) alpha) protein and mRNA
      were greater in day 12 conceptuses than in conceptuses from all other days.
      However, transition from the tubular to the filamentous form on day 12 postmating
      was associated with a dramatic decline in the level of P450(17) alpha) mRNA. The
      conceptus 17 beta-estradiol concentration was highly correlated with
      immunoreactive P450(17) alpha) protein and hybridizable P450(17) alpha) mRNA over
      days 12, 14, 16, and 21 postmating. These data suggest that the decrease in
      blastocyst estrogen secretion occurring after the time of elongation in porcine
      conceptuses may be due to a decrease in P450(17) alpha expression.

PMID- 1379166
TI  - Competition for binding to insulin-like growth factor (IGF) binding protein-2, 3,
      4, and 5 by the IGFs and IGF analogs.
AB  - The insulin-like growth factors (IGF) I and II bind to IGF binding proteins (BP)
      with high affinity. The affinity of each of the IGFs for individual BPs and the
      regions of the IGF-I molecule that are required for this high affinity binding
      have been defined only for IGFBP-1 and IGFBP-3. The present studies have
      determined the affinity of several IGF analogs (prepared using in vitro
      mutagenesis) for pure IGFBP-2, 3, 4, and 5. The results show IGFBP-2 binds these
      analogs in a manner similar to IGFBP-1. For example, a mutation in the A chain
      region (positions 49, 50, 51) or B chain (positions 3, 4) results in greater than
      20-fold reduction in affinity for either IGFBP-1 or 2. In contrast, mutations in
      the A chain region have minimal effect on binding to IGFBP-3, whereas
      substitutions at the 3, 4, 15, 16 positions of the B chain reduce IGF-I affinity
      by at least 50-fold. At pH 7.4, binding of the analogs to IGFBP-4 is less
      affected by substitutions at the B chain 3, 4 positions compared to IGFBP-1, 2,
      and 3, but IGFBP-4 affinity for analogs containing the A chain substitutions is
      greatly reduced similarly to IGFBP-1 and 2. Binding to IGFBP-5 is greatly reduced
      by either A or B chain substitutions and most of the mutations result in greater
      than 100-fold reduction in affinity. Acidic pH 6.0 was associated with increased
      affinity of IGFBP-4 for the A chain containing mutants. The results indicate that
      only IGFBP-1 and 2 have nearly identical affinity for each of these analogs,
      whereas IGFBP-3, 4, and 5 have similarities and significant differences. The
      findings suggest that different binding proteins have differential structural
      requirements for optimal IGF-I binding.

PMID- 1379168
TI  - In vitro evidence for modulation of morphological and functional development of
      hypothalamic immunoreactive atrial natriuretic peptide neurons by cyclic 3',5'
      adenosine monophosphate.
AB  - In the hypothalamus of the rat, the precursor of atrial natriuretic peptide (ANP)
      is produced and processed into its smaller congeners of 3K mol wt species, which
      are secreted from neurons with cell bodies in the periventricular areas and the
      paraventricular nuclei of the tissue. Employing long term monolayer cultures of
      neonatal rat hypothalamic cells, we have identified a small population of cells
      that stained positive for immunoreactive (ir) ANP. Seventy-two +/- 7% (mean +/-
      SE; n = 4 per 1000 cells) of the irANP positive cells were colocalized with the
      staining of neuron-specific enolase; some of the cells possessed multiple
      neurites and showed irANP staining in the perikarya, in the varicosities along
      neuronal processes, and at the terminals of long neurites. Over the range of 10(
      6)-10(-4) M, forskolin, 3-isobutyl-1-methylxanthine, or 8-bromo-cAMP
      significantly augmented the total number of irANP-positive cells and those
      possessing neurites in a dose-related and time-dependent manner. At 10(-4) M, 4
      days of forskolin treatment increased the number of irANP-positive neurons 4-fold
      (P less than 0.01) while tripling that of the cells with long neurites (P less
      than 0.01). Furthermore, it approximately tripled the number of cells (P less
      than 0.01) showing positive signals for pro-ANP mRNA, as ascertained by
      colorimetric in situ hybridization using a 30-basepair antisense oligonucleotide
      probe labeled with digoxigenin. Consistent with the above observation, forskolin,
      3-isobutyl-1-methylxanthine, or 8-bromo-cAMP treatment significantly augmented
      the total amount of irANP present in the cultures, with an ED50 of forskolin
      approximating 5 x 10(-5) M. Although treatment with 10(-7) M phorbol 12-myristate
      13-acetate approximately doubled the production of irANP in the cultures (P less
      than 0.05), phorbol 12-myristate 13-acetate had little effect on modulating the
      number or neurite outgrowth of irANP neurons. Thus, our present findings suggest
      that protein kinase-A pathways are of greater importance than protein kinase-C
      pathways in regulating both the functional and morphological development of ANP
      producing neurons during the ontogenesis of the rat hypothalamus.

PMID- 1379169
TI  - Gonadotropin-releasing hormone-induced calcium signaling in clonal pituitary
      gonadotrophs.
AB  - In agonist-stimulated clonal pituitary gonadotrophs (alpha T3-1 cells),
      cytoplasmic calcium ([Ca2+]i) exhibited rapid and prominent peak increases,
      followed by lower, but sustained, elevations for up to 15 min. The [Ca2+]i
      response to GnRH was rapidly inhibited by prior addition of a potent GnRH
      antagonist. In the absence of extracellular Ca2+ the initial peak [Ca2+]i
      response was only slightly decreased, but the prolonged increase in [Ca2+]i was
      abolished, indicating that the peak is derived largely from intracellular calcium
      mobilization and the sustained phase from Ca2+ influx. Application of the
      endoplasmic reticulum Ca(2+)-ATPase blocker thapsigargin caused progressive and
      dose-dependent elevation of [Ca2+]i and decreased the peak amplitude of the GnRH
      induced Ca2+ response. On the other hand, addition of dihydropyridine calcium
      channel antagonists before or after GnRH treatment prevented or terminated the
      plateau phase, respectively, consistent with entry of Ca2+ through L-type voltage
      sensitive Ca2+ channels (VSCC) as the major Ca2+ influx pathway during GnRH
      action. The presence of L-type VSCC in alpha T3-1 cells was further indicated by
      the ability of elevated extracellular K+ levels and the dihydropyridine calcium
      channel agonist Bay K 8644 to elevate [Ca2+]i in an extracellular calcium
      dependent manner. These actions of depolarization and Bay K 8644 were inhibited
      by nifedipine, with an IC50 of 10 nM. High extracellular K(+)- and GnRH-induced
      Ca2+ entry was also attenuated by phorbol esters and permeant diacylglycerols,
      indicating that protein kinase-C exerts inhibitory modulation of VSCC activity.
      In contrast to normal pituitary gonadotrophs, in which GnRH induces a frequency
      modulated oscillatory [Ca2+]i response, single alpha T3-1 cells exhibited a
      nonoscillatory amplitude-modulated signal during agonist stimulation. The [Ca2+]i
      responses observed in alpha T3-1 gonadotrophs indicate that the immortalized
      cells retain functional GnRH receptors and their coupling to the Ca2+ signaling
      pathway. Ca2+ influx through L-type channels maintains the plateau phase of the
      [Ca2+]i response during agonist stimulation and is inhibited by activation of
      protein kinase-C.

PMID- 1379171
TI  - Opposite vectorial secretion of insulin-like growth factor I and its binding
      proteins by pig Sertoli cells cultured in the bicameral chamber system.
AB  - A two-chamber system has been employed to investigate the vectorial secretion of
      insulin-like growth factor I (IGF-I) and its binding proteins (IGF-BPs) by pig
      Sertoli cells. The kinetics of transport of [3H]insulin as well as the
      transepithelial electrical resistance of filters coated with reconstituted
      basement membrane, in the absence of presence of Sertoli cells, indicated the
      formation of a functional barrier by Sertoli cells. The rates of diffusion of
      [125I]IGF-I or [125I]human CG were slower from the apical (AC) to the basal (BC)
      compartment than in the opposite direction. However, the IGF-I content and
      concentration in the BC was twice that seen in the AC. FSH increased the
      secretion of IGF-I in the BC, and therefore increased the BC/AC ratio. In
      contrast, most of the IGF-BPs, with apparent molecular sizes of 39-43, 34, 29 and
      24 kDa, were secreted in the AC. FSH increased the secretion of IGF-BP 39-43 kDa
      (BP3). This is the first report of opposite vectorial secretion of IGF-I and its
      binding protein by any cell type.

PMID- 1379170
TI  - Evidence that the FSH receptor itself is not a calcium channel.
AB  - FSH has been shown to stimulate the uptake of calcium in cultured rat Sertoli
      cells, resulting in an increase in cytosolic calcium concentrations. One
      possibility which has been put forth is that the FSH receptor per se may act as a
      calcium channel. This is all the more tantalizing given the proposed structure of
      this receptor which, like all other G protein-coupled receptors, is thought to
      have the putative transmembrane helices forming a bundle-like structure in the
      plasma membrane. To test whether the FSH receptor could function as a calcium
      channel, we performed whole-cell voltage clamp experiments on 293 and 293F(wt1)
      cells, which are a clonal line of 293 cells expressing high levels of rat FSH
      receptors. The 293 cells, which do not express FSH receptors, were found to lack
      any detectable inward calcium currents, and therefore, serve as an excellent
      model for transfecting with potential calcium conducting FSH receptors. When the
      293F(wt1) cells were then tested, no inward calcium currents could be detected in
      either control or FSH-stimulated cells. These results suggest that the FSH
      receptor itself is not a calcium channel and, therefore, FSH must be stimulating
      endogenous calcium channels in rat Sertoli cell plasma membranes.

PMID- 1379172
TI  - pH dependence and exchange of high and low responder peptides binding to a class
      II MHC molecule.
AB  - We have compared the binding kinetics of two antigenic peptides to a soluble
      class II MHC molecule. One of the peptides provokes a strong T cell response and
      the other a much weaker one. Both show greatly increased (approximately 40-fold)
      association rates at pH 5 in comparison to neutral pH, consistent with the low pH
      environment of late endosomes being most conducive to class II MHC--peptide
      binding. Interestingly, the weak peptide has a much faster off-rate that is
      significantly increased at pH 5 and it can be entirely replaced in an exchange
      reaction by the stronger one. This suggests that one characteristic of
      immunodominant peptides is that of nearly irreversible binding, such that they
      will be strongly selected for in the course of class II MHC transit and recycling
      through endosomal compartments. Modelling the parameters of this peptide exchange
      also suggests that a large fraction of the GPI-chimeric MHC molecules used in
      this study are 'empty' with respect to endogenous peptides, or else occupied with
      extremely weak ones, consistent with their inability to load processed peptides
      intracellularly.

PMID- 1379173
TI  - A mechanosensitive ion channel in Schizosaccharomyces pombe.
AB  - Protoplast protuberances (blebs) of Schizosaccharomyces pombe were examined using
      the patch-clamp technique. In addition to several voltage-gated ion channels, we
      encountered the activities of a mechanosensitive ion channel with a conductance
      of 180 pS. Microscopic currents of one or two units were observed in some excised
      patches and ensemble currents of several tens of units were observed in all blebs
      examined in whole-bleb configuration. This channel opens at pressures of cm Hg
      applied to whole blebs and it passes cations, including Ca2+. It is inactivated
      by membrane depolarizations and blocked by Gd3+. We discuss the possible
      functions of such a channel, including its activation upon cell cycle dependent
      cytoskeletal reorganizations.

PMID- 1379174
TI  - Two different protein kinases act on a different time schedule as glial filament
      kinases during mitosis.
AB  - Glial fibrillary acidic protein (GFAP) is a component of glial filaments specific
      to astroglia. We now report the spatial and temporal distributions of four
      phosphorylated sites in the GFAP molecule during mitosis of astroglial cells,
      determined by antibodies which can distinguish phosphorylated epitopes from non
      phosphorylated-epitopes. Immunofluorescence microscopy showed that the Ser8
      residues in the entire cytoplasmic glial filament system are initially
      phosphorylated when the cells enter mitosis. In cytokinesis, the phosphoSer8
      residues become dephosphorylated, whereas Thr7, Ser13 and Ser34 in glial
      filaments at the cleavage furrow become the preferred sites of phosphorylation.
      The cdc2 kinase purified from mitotic cells can phosphorylate GFAP at Ser8 but
      not at Thr7, Ser13 or Ser34, in vitro. These results suggest that cdc2 kinase
      acts as a glial filament kinase only at the G2-M phase transition while other
      glial filament kinases are probably activated at the cleavage furrow before final
      separation of the daughter cells.

PMID- 1379176
TI  - Three widely separated positions in the 16S RNA lie in or close to the ribosomal
      decoding region; a site-directed cross-linking study with mRNA analogues.
AB  - Synthetic mRNA analogues were prepared by T7 transcription, each containing
      several thio-uridine residues at selected positions. After binding to the
      ribosome in the presence of cognate tRNA, the thio-U residues were activated by
      UV irradiation and the resulting sites of cross-linking to 16S RNA analysed.
      Three distinct cross-links were consistently observed: (i) from position '+6' of
      the mRNA (the 3'-base of the A-site codon) to base 1052 of 16S RNA; (ii) from
      position '+7' of the mRNA to base 1395; and (iii) from '+11' to base 532.
      Individual yields of the cross-links were strongly dependent on the particular
      mRNA sequence in each case. The '+11/532' and '+6/1052' cross-links were always
      entirely tRNA-dependent, whereas the '+7/1395' cross-link was observed at lower
      intensity in the absence of tRNA. In the presence of a second (A-site bound) tRNA
      the +6/1052 cross-link was markedly reduced. A cross-link to the 1050 region was
      again observed when a message carrying a thio-U at position '+9' was translocated
      on the ribosome so as to bring the thio-U to position +6. Taken together, the
      data are incompatible with some current models both for the three-dimensional
      arrangement of 16S RNA and for the orientation of the tRNA-mRNA complex in the
      ribosome.

PMID- 1379175
TI  - Human papillomavirus E6 proteins bind p53 in vivo and abrogate p53-mediated
      repression of transcription.
AB  - The transforming proteins of DNA tumor viruses SV40, adenovirus and human
      papillomaviruses (HPV) bind the retinoblastoma and p53 cell cycle regulatory
      proteins. While the binding of SV40 large T antigen and the adenovirus E1B 55 kDa
      protein results in the stabilization of the p53 protein, the binding of HPV16 and
      18 E6 results in enhanced degradation in vitro. To explore the effect of viral
      proteins on p53 stability in vivo, we have examined cell lines immortalized in
      tissue culture by HPV18 E6 and E7 or SV40 large T antigen, as well as cell lines
      derived from cervical neoplasias. The half-life of the p53 protein in non
      transformed human foreskin keratinocytes in culture was found to be approximately
      3 h while in cell lines immortalized by E6 and E7, p53 protein half-lives ranged
      from 2.8 h to less than 1 h. Since equivalent levels of E6 were found in these
      cells, the range in p53 levels observed was not a result of variability in
      amounts of E6. In keratinocyte lines immortalized by E7 alone, the p53 half-life
      was found to be similar to that in non-transformed cells; however, it decreased
      to approximately 1 h following supertransfection of an E6 gene. These
      observations are consistent with an interaction of E6 and p53 in vivo resulting
      in reductions in the stability of p53 ranging between 2- and 4-fold. We also
      observed that the expression of various TATA containing promoters was repressed
      in transient assays by co-transfection with plasmids expressing the wild-type p53
      gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379177
TI  - Co-ordinate expression of the two threonyl-tRNA synthetase genes in Bacillus
      subtilis: control by transcriptional antitermination involving a conserved
      regulatory sequence.
AB  - In Bacillus subtilis, two genes, thrS and thrZ, encode distinct threonyl-tRNA
      synthetase enzymes. Normally, only the thrS gene is expressed. Here we show that
      either gene, thrS or thrZ, is sufficient for normal cell growth and sporulation.
      Reducing the intracellular ThrS protein concentration induces thrZ expression in
      a dose-compensatory manner. Starvation for threonine simultaneously induces thrZ
      and stimulates thrS expression. The 5'-leader sequences of thrS and thrZ contain,
      respectively, one and three transcription terminators preceded by a conserved
      sequence. We show that this sequence is essential for the regulation of thrS via
      a transcriptional antitermination mechanism. We propose that both genes, thrS and
      thrZ, are regulated by the same mechanism such that the additional regulatory
      domains present before thrZ account for its non-expression. In contrast to
      Escherichia coli, structurally similar regulatory domains, i.e. the consensus
      sequence preceding a terminator structure, are found in the leader regions of
      most aminoacyl-tRNA synthetase genes of Gram-positive bacteria. This suggests
      that they are regulated by a common mechanism.

PMID- 1379178
TI  - Poliovirus RNA recombination: mechanistic studies in the absence of selection.
AB  - Direct and quantitative detection of recombinant RNA molecules by polymerase
      chain reaction (PCR) provides a novel method for studying recombination in RNA
      viruses without selection for viable progeny. The parental poliovirus strains
      used in this study contained polymorphic marker loci approximately 600 bases
      apart; both exhibited wild-type growth characteristics. We established conditions
      under which the amount of PCR product was linearly proportional to the amount of
      input template, and the reproducibility was high. Recombinant progeny were
      predominantly homologous and arose at frequencies up to 2 x 10(-3). Recombination
      events increased in frequency throughout replication, indicating that there is no
      viral RNA sequestration or inhibition of recombination late in infection as
      proposed in earlier genetic studies. Previous studies have demonstrated that
      poliovirus recombination occurs by a copy-choice mechanism in which the viral
      polymerase switches templates during negative-strand synthesis. Varying the
      relative amount of input parental virus markedly altered reciprocal recombination
      frequencies. This, in conjunction with the kinetics data, indicated that acceptor
      template concentration is a determinant of template switching frequency. Since
      positive strands greatly outnumber negative strands throughout poliovirus
      infection, this would explain the bias toward recombination during negative
      strand synthesis.

PMID- 1379179
TI  - Comparison of acyltransferase-mediated mutagenicity and nucleic acid binding of N
      acetoxy-4-acetylaminobiphenyl by hepatic and bladder microsomes from rats and
      dogs.
AB  - Acyltransferase-mediated mutagenic and metabolic activation of N-acetoxy-4
      acetylaminobiphenyl (N-OAc-AABP) by hepatic tissues of rats and dogs were
      compared. N-OAc-AABP was mutagenic in Salmonella typhimurium TA98 even in the
      absence of exogenous enzyme(s). However, supplementation with hepatic microsomes
      from dogs showed a dose-dependent increase in mutagenicity of N-OAc-AABP, whereas
      under the same conditions, rat microsomes were inactive. Incubation of liver
      microsomes with RNA showed that 46.4 and 11.2 nmole of [3H]N-OAc-AABP were
      bound/mg RNA/mg protein with dogs and rats, respectively. The hepatic microsome
      mediated binding and mutagenicities of N-OAc-AABP were blocked by paraoxon,
      suggesting the involvement of deacetylase(s) in the activation process. Analyses
      of the in vitro incubates of N-OAc-AABP with rat and dog liver microsomes
      revealed the O-deacetylation product N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP)
      as the major metabolite. The ratios of O-deacetylation of N-O[14C]Ac-AABP versus
      N-deacetylation of N-OAc-[14C]AABP for hepatic microsomes from dogs and rats were
      2.9 and 7.2, respectively. The O- and N-deacetylases are also distributed in
      bladder tissues and their activities in comparison to the hepatic tissues were
      lower and amounted to 14.2 and 5.0 nmoles (O/N-deacetylation ratio 2.8) for dogs
      and 14.8 and 1.7 nmoles per mg protein per min (O/N-ratio of 8.7) for rats. The
      microsomes from bladder tissues also catalyzed the binding of [3H]N-OAc-AABP to
      RNA and enhanced its mutagenic response in TA98, both of which were blocked by
      paraoxon. The occurrence of deacetylase(s) in the target tissues of the bladder
      carcinogen 4-acetylaminobiphenyl (AABP) suggests that metabolic activation of
      some of the proximate metabolites could occur within these target organs.
      Furthermore, since the O-deacetylation product N-OH-AABP is relatively innocuous
      compared to the N-deacetylation product N-acetoxy-4-aminobiphenyl, these results
      imply that the refractiveness of rats for 4-aminobiphenyl or AABP-induced bladder
      carcinogenesis might in part be associated with the higher ratios of microsomal
      O/N-deacetylase activities. Thus susceptibility to arylamine or arylacetamide
      induced liver and bladder carcinogenesis might be influenced by the microsomal
      deacetylases.

PMID- 1379180
TI  - MPM-12: a monoclonal antibody that predominantly stains mitotic cells and
      recognizes a protein kinase.
AB  - The monoclonal antibody MPM-12, raised by using partially purified extract of
      mitotic HeLa cells as the immunogen, preferentially stains the cytoplasm of
      mitotic cells by indirect immunofluorescence without exhibiting any species
      specificity. On immunoblots, MPM-12 recognizes three bands, of 155, 88, and 68
      kDa, in mitotic HeLa cell extract but only the 68-kDa band in interphase cell
      extract. The 68-kDa band seems to be associated with chromatin while the other
      two are not. All three MPM-12 reactive peptides are phosphorylated, and the
      phosphorylation seems to be required for MPM-12 reactivity. The MPM-12
      immunocomplexes exhibit autophosphorylating and histone H1 kinase activity.

PMID- 1379181
TI  - Microinjection of IFA antibody induces intermediate filament aggregates in
      epithelial cell lines but perinuclear coils in fibroblast-like lines.
AB  - The murine monoclonal IFA antibody recognizes a conserved sequence present in
      almost all intermediate filament (IF) proteins. When IFA antibody was injected
      into 13 different primary or established cell lines, striking differences were
      detected between epithelial and fibroblastic cell lines. In epithelial cells
      keratin IFs were broken down within 4 h into numerous spheroid aggregates
      scattered throughout the cytoplasm. Keratin aggregates were first detected in the
      cytoplasmic periphery. In contrast, in fibroblastic cells, injection of IFA
      antibody led to the formation of perinuclear coils of vimentin. IFA antibody at a
      concentration of greater than 1 mg/ml had to be injected to initiate these
      transitions. When HeLa cells, which contain separate networks of vimentin and
      keratin filaments, were injected with IFA antibody, vimentin did not form
      perinuclear coils but was instead found together with keratin in aggregates.
      Electron micrographs of HeLa cells injected with IFA antibody showed that the
      aggregates have diameters between 0.5 and 2.6 microns and resembled the keratin
      aggregates observed in certain mitotic epithelial cells. Although the
      ultrastructural studies support an association of some aggregates with
      desmosomes, aggregates were, however, also induced by injection of IFA antibody
      into human keratinocytes in low calcium medium under conditions where desmosomes
      were not present.

PMID- 1379182
TI  - A method for rapid screening of recombinant proteins for recognition by T
      lymphocytes.
AB  - A simple, cost-effective method is described that allows rapid screening of
      recombinant protein sequences for their ability to stimulate T cells. Individual
      microcultures of E. coli each expressing a gene product or peptide sequence fused
      to protein A are grown in 96-well plates. Following lysis of the bacteria, the
      fusion peptide is readily captured with immobilized immunoglobulin in tissue
      culture wells. No further purification is required. T lymphocytes plus
      appropriate antigen-presenting cells are added directly to the wells and assayed
      for proliferation. The DNA in bacteria from wells stimulating T cell
      proliferation is then sequenced. The technique allows rapid mapping of T cell
      epitopes by facilitating screening of truncation mutants without extensive
      purification. Described here is a further application of the technique to study
      monosubstituted analogues of a known T cell epitope.

PMID- 1379183
TI  - Subjugation of dominant immunogenic determinants within a chimeric peptide.
AB  - The mechanism of immunodominance was investigated using chimeric peptides from
      mouse myelin basic protein consisting of the immunodominant I-Au-restricted Ac1
      11, attached by a peptide bond to I-Eu-restricted 35-47. Our results indicate
      that this chimeric peptide and certain of its derivatives were excellent
      immunogens both in vitro and in vivo. Notably, on immunization with Ac1-11:35-47
      or Ac1-11 (Ala4):35-47, the proliferative T cell responses to each of its
      component peptides were almost completely "subjugated" in favor of neo
      determinants that are I-Eu restricted. Furthermore, each of 11 hybridomas derived
      after immunization with Ac1-11:35-47 had specificity for junctional neo
      determinants and none could be stimulated to produce interleukin-2 from Ac1-11 or
      35-47. Subjugation of the immunogenicity of the original determinants occurred
      regardless of their dominance when separate. It did not appear to result from non
      availability of the original determinants because the chimeric peptide was able
      to induce neonatal tolerance to each of its constituents. These results indicate
      that in an overlapping multideterminant array, the dominant determinant is
      unpredictable from historical data about any of the components. Determinant
      choice, at any stage of processing, may be governed by competitive aspects of
      determinant capture in an environment where all components--antigen, major
      histocompatibility complex and T cell receptor--are available.

PMID- 1379184
TI  - Adhesion molecule-mediated signals regulate major histocompatibility complex
      unrestricted and CD3/T cell receptor-triggered cytotoxicity.
AB  - Appropriate experimental conditions were devised to demonstrate that CD58 (LFA
      3), CD54 (ICAM-1) and CD11a/CD18 (LFA-1) adhesion molecules are the source of
      signals that regulate nonspecific major histocompatibility complex-unrestricted
      and CD3/T cell receptor (TcR)-triggered cytotoxicity. Using anti-LFA-3 monoclonal
      antibody (mAb)-treated, interleukin-2 (IL-2)-cultured peripheral blood
      lymphocytes (PBL) or cloned CD3+/CD8+ cells as lymphocyte-activated killer (LAK)
      effectors, and ligand (CD2)-negative tumor cell lines as targets, a down
      regulation of CD3- and CD3+ cell-mediated LAK activity was consistently observed.
      Anti-LFA-3 mAb also down-regulated tumor cell lysis when T cell clones were
      triggered to kill P815 cells through stimulation of the CD3/TcR complex by an
      anti-CD3 mAb. The inhibitory effect of anti-LFA-3 mAb was not prevented by
      stimulatory anti-CD2 mAb. Anti-ICAM-1 mAb treatment of IL-2-cultured PBL
      consistently up-regulated LAK cytotoxicity against tumor target cells. However,
      this effect was only exerted on CD3- LAK effectors. Anti-LFA-1 mAb blocked
      conjugate formation between effector cells and tumor target cells, thus rendering
      this model unsuitable to evaluate the regulatory role of LFA-1. Therefore, a
      cytotoxicity model system was applied in which a hybrid anti-CD3/anti-human red
      blood cell (HuRBC) mAb triggers cytolytic T cells to lyse HuRBC. In these
      experiments, anti-LFA-1 mAb markedly up-regulated the lytic ability of IL-2
      cultured PBL. We conclude that mAb against LFA-3, ICAM-1 and LFA-1 molecules
      deliver regulatory signals for LAK cells and cytotoxic T lymphocytes. As these
      stimuli may be delivered by ligands expressed on tumor targets as well as on
      other immune competent and inflammatory cells, the present observations are
      relevant in the context of both the host's immune response against tumors and the
      general functioning of the immune system.

PMID- 1379185
TI  - Virus infection blocks the processing and presentation of exogenous antigen with
      the major histocompatibility complex class II molecules.
AB  - Helper T cell recognition of antigen requires that antigen be processed and
      presented by class II expressing antigen-presenting cells (APC). Many antigens
      presented by the immune system are part of infectious organisms, for example,
      bacteria and viruses, which themselves may affect APC function. Here we show that
      infection of B cell lines as APC with viruses of two different families, namely,
      influenza A or vaccinia, completely block processing and presentation of an
      exogenous globular protein antigen pigeon cytochrome c. The block appears to be
      primarily within the processing pathway, as virus infection has little effect on
      the presentation of an antigenic peptide of pigeon cytochrome c which does not
      require processing. It is likely that several steps in the processing pathway are
      affected. Only live infectious virus, not UV-inactivated virus blocks APC
      function, indicating that there is no competition of viral particles with
      cytochrome c for the class II processing machinery. As compared to uninfected
      cells, virus-infected cells internalize less antigen bound to surface Ig but
      degrade a similar portion of that which enters the cell. Virus infection results
      in reduced protein synthesis in APC which may also be a factor in decreasing APC
      function. Significantly, we show that the processing of a high affinity
      evolutionary variant of cytochrome c from Drosophila melanogaster is reduced less
      by virus infection as compared to c. Such knowledge may guide the selection of
      antigenic epitopes in vaccine design.

PMID- 1379186
TI  - Identification of a source of biologically active CD40 ligand.
AB  - We have identified the murine thymoma line EL4 as a source of biologically active
      CD40 ligand. Using a biotin-labeled soluble CD40.Fc fusion protein, consisting of
      the extracellular domain of human CD40 and the Fc region of human IgG1, EL4 cells
      were subjected to repeated flow cytometric cell sorting to select for cells with
      enhanced biotinylated CD40.Fc binding. After nine rounds of sorting, the number
      of CD40.Fc binding sites/cell had risen from 450 on the unsorted parental EL4
      cells to 15,000 on EL40.9 cells (EL4 cells sorted with biotinylated CD40.Fc for
      nine rounds). Scatchard analysis of radiolabeled CD40.Fc binding revealed that
      the surface-expressed CD40 ligand on parental EL4 and EL40.9 cells bound its
      receptor with a single class of high-affinity sites (Kd = 0.5 nM). Supernatant
      (SN) from the sorted EL40.9 cells was found to contain human and murine B cell
      stimulatory activity which could be removed by preclearing with immobilized
      CD40.Fc, confirming the presence of soluble CD40 ligand in the preparations.
      EL40.9 supernatant enhanced soluble CD23 (sCD23) release and induced IgE
      secretion from interleukin 4-stimulated human B cells. In addition, EL40.9 SN
      contained proliferative activity for anti-IgM-activated murine B cells which
      could be removed by treatment with immobilized CD40.Fc. However, the same SN had
      no demonstrable activity on the proliferation of human B cells. The results
      presented here describe, for the first time, a source of membrane-bound and
      soluble CD40 ligand. The soluble form of this murine ligand has activity on
      murine and human B cells and induces some of the functional responses predicted
      for the ligand based on the action of stimulatory antibodies directed against the
      human CD40 surface molecule.

PMID- 1379187
TI  - T and B cell receptors discriminate major histocompatibility complex class II
      conformations influenced by the invariant chain.
AB  - Direct recognition of major histocompatibility complex (MHC) molecules may occur
      when T cells are positively selected in the thymus and also during recognition of
      non-self MHC molecules. Since peptide recognition and binding of particular
      monoclonal antibodies is strongly influenced by the invariant chain (Ii) of the
      class II molecule, we have asked whether Ii also affects recognition of non-self
      MHC molecules by T cells. We find that Ii binding alters MHC class II
      conformation as detected by a monoclonal antibody, and that this alteration is
      retained in cell surface MHC class II molecules after Ii dissociates. This
      altered conformation also affects recognition by allogeneic T cells. Normal T
      cells and T cell clones preferentially recognize MHC class II molecules that have
      been associated with Ii, suggesting that thymic selection may be influenced by
      MHC conformation independently of specific peptide binding.

PMID- 1379188
TI  - Processing and presentation of ovalbumin in mice genetically selected for
      antibody response.
AB  - Lines of mice selected for high or low antibody production to sheep red blood
      cells (H-I and L-I) were studied for their ability to process and present
      ovalbumin to a panel of 12 T-T hybridomas in two different H-2 haplotypes. When H
      I and L-I spleen cells were used as antigen-presenting cells, no difference could
      be observed in the peptide generation by these mice compared to H-2-compatible
      B.10.Q and B.10.S spleen cells, respectively. Neither normal splenic L-I B-cells
      nor L-I thioglycolate-induced peritoneal macrophages were defective at presenting
      native ovalbumin, to six and eight different I-As-restricted T-T hybrids,
      respectively. Altogether, these results differ from previous findings which had
      indicated a deficiency in the processing and presentation of antigen by the low
      line, L-I.

PMID- 1379189
TI  - Restricted alpha/beta receptor gene usage of idiotype-specific major
      histocompatibility complex-restricted T cells: selection for CDR3-related
      sequences.
AB  - We have sequenced the T cell receptor (TcR) V alpha and V beta genes of seven
      independent BALB/c CD4+ T cell clones specific for the immunoglobulin lambda 2
      light chain produced by the MOPC 315 myeloma (lambda 2(315)). All the clones
      recognize a peptide of residues 91-101 of lambda 2(315) and are restricted by the
      major histocompatibility complex (MHC) molecule I-E(d). The results indicate that
      in BALB/c mice, this anti-idiotypic response uses a very limited number of TcR.
      The four clones which cross-react between Phe94 and Tyr94 peptide analogues use
      very similar receptors (V alpha 3, J alpha 1, V beta 6, J beta 1.1). The V alpha
      3 gene used by all of these clones is identical and has not been previously
      described. Although the four clones differ in nucleotide sequence in the V/J
      borders, two had identical receptors at the amino acid level. One of the cross
      reactive clones exhibits a heteroclitic response to the Tyr94 peptide variant
      resulting from a single amino acid exchange in the V/J junction of the alpha
      chain. The three remaining clones which recognize only the Phe94 and not the
      Tyr94 peptide have somewhat more diverse TcR, however, two of these three clones
      use V beta 6. One of these non-crossreacting clones is alloreactive, the
      specificity of which can be attributed to differences in the N-D-J sequences.
      Taken together these data indicate that this T cell response to an immunoglobulin
      idiotope is very restricted in terms of the TcR used. These data in conjunction
      with recently published results indicate that, although there can be strong
      preference for individual V alpha or V beta gene segments, certain V alpha/V beta
      combinations are preferentially selected for interacting with a given peptide/MHC
      combination, and that the CDR3-related regions are crucial for antigen fine
      specificity and alloreactivity.

PMID- 1379190
TI  - Inhibition of membrane currents and rises of intracellular Ca2+ in PC12 cells by
      CGS 9343B, a calmodulin inhibitor.
AB  - The calmodulin inhibitor 1,3-dihydro-1-[1-((4-methyl-4H,6H-pyrrolo[1,2-a]
      [4,1]benzoxazepin - 4-yl)methyl)-4-piperidinyl]-2H-benzimidazol-2-one maleate
      (CGS 9343B) caused a reversible block of voltage-activated Ca2+, Na+, and K+
      currents in differentiated rat pheochromocytoma (PC12) cells. The drug also
      inhibited nicotinic acetylcholine receptor (nAChR) channel currents but not
      inward currents evoked by extracellular ATP. Depolarization-induced intracellular
      Ca2+ transients were almost completely inhibited in growth cones and cell bodies
      by CGS 9343B. Our results suggest actions of CGS 9343B on ion fluxes unrelated to
      calmodulin inhibition.

PMID- 1379191
TI  - Expression of alpha 6 beta 4 integrin increases during malignant conversion of
      mouse epidermal keratinocytes: association of beta 4 subunit to the cytokeratin
      fraction.
AB  - The expression of alpha 6 beta 4 integrin has been analyzed in several
      keratinocyte cell lines representative of various stages of mouse epidermal
      carcinogenesis. The immunological analyses carried out show that alpha 6 beta 4
      is expressed at the cell surface of the cell lines which exhibit an epithelial or
      epithelioid morphology. The relative levels of alpha 6 beta 4 expressed at the
      cell surface increase noticeably from premalignant to malignant cells, as
      detected by fluorescence flow cytometry. This increase also correlates with the
      abundance of soluble beta 4 subunit detected by Western immunoblotting in the
      different cell lines. However, complete absence of alpha 6 beta 4 has been found
      in spindle carcinoma cells showing a fibroblast-like phenotype in culture. The
      integrin remains associated to detergent- and high salt-insoluble cytoskeletal
      components, organized in stable anchoring contacts, as in human keratinocytes
      (Carter et al., J. Cell Biol., 111, 3141, 1990). In addition, a significant
      fraction of the beta 4 subunit is detected associated to highly purified
      cytokeratin fractions. These results, together with those regarding the
      organization of both cellular components in drug-treated cells, support the
      existence of a close association between alpha 6 beta 4 and the intermediate
      filaments of the cytoskeleton.

PMID- 1379192
TI  - Expression of microinjected DNA and RNA in early rabbit embryos: changes in
      permissiveness for expression and transcriptional selectivity.
AB  - Gene expression in rabbit early development was investigated by microinjecting
      LacZ DNA and LacZ RNA in 1-cell and 2-cell embryos. Expression of LacZ DNA could
      not be obtained before 30-36 hpf, although synthetic LacZ RNA was translated from
      12 hpf at the least. The onset of expression of microinjected DNA correlated with
      the 8- to 16-cell stage. This suggests that before this stage, there is a general
      negative control of gene expression. The arrest of in vitro development at the 2-
      to 8-cell stages did not inhibit LacZ expression, which still occurred at 33 hpf.
      In addition the inhibition of the first cleavage by nocodazole resulted in LacZ
      expression in 1-cell embryos. Expression of microinjected DNA thus occurs at a
      fixed time after fertilization and is independent of cleavages and of the second
      and subsequent DNA replications. Therefore, the changes in permissiveness for the
      expression of microinjected DNA in rabbit embryos are reminiscent of those in
      mouse embryos. Transcriptional selectivity in rabbit embryos was compared to that
      in early mouse embryos. In both species, Sp1-sensitive promoters were active and
      the promoter of simian virus 40 did not require far upstream enhancers before
      late cleavage stages; genes driven by the -447, +563 region of murine leukemia
      virus were repressed. In rabbit, however, the H-2Kb promoter active in mouse was
      silent. Altogether, the results illustrate a remarkable conservation of the
      characteristics of the transcription in early rabbit and mouse embryos and the
      independence of its resumption from the pattern of cleavage.

PMID- 1379193
TI  - E-cadherin expression during the acidic FGF-induced dispersion of a rat bladder
      carcinoma cell line.
AB  - Cell dissociation and acquisition of cell motility are major events in
      morphogenesis, wound repair, and cancer invasion and metastasis. We have used the
      NBT-II bladder carcinoma cell line as a model system to study the mechanisms of
      these events. Upon exposure to acidic fibroblast growth factor (aFGF), NBT-II
      cells undergo morphological changes that resemble those described in epithelial
      mesenchymal transitions, i.e., dissociation of some or all polygonal epithelial
      cells and their transformation into motile, fibroblastic-like cells. The
      disruption of intercellular contacts, which accompanies cell dissociation and
      acquisition of motility, is correlated with a redistribution of E-cadherin, a
      Ca(2+)-dependent cell adhesion molecule, over the entire cell surface and within
      the cytoplasm. However, these modifications are not accompanied by a reduction of
      the intercellular adhesiveness or a loss of E-cadherin expression. Moreover, the
      formation of intercellular contacts between fibroblastic-like NBT-II cells
      results in the relocation of epithelial cadherin (E-cadherin) immunoreactivity on
      lateral membranes, but is not sufficient to abrogate cell motility. Finally, the
      overexpression of E-cadherin by NBT-II cells stably transfected with a plasmid
      containing the mouse E-cadherin cDNA does not impair the scattering effect of
      aFGF, indicating that high levels of E-cadherin expression do not prevent cells
      from disrupting their intercellular connections. Altogether, these results
      suggest that the scattering activity of aFGF is not mediated by direct
      modulations of E-cadherin expression.

PMID- 1379194
TI  - Characterization of human umbilical vein endothelial cell lines produced by
      transfection with the early region of SV40.
AB  - Human umbilical vein endothelial cells were transfected by electroporation with
      the plasmid pSV3neo, containing the early region of simian virus 40. The
      resultant "cell lines" divide rapidly (population doubling time of 33 h) for up
      to 24 passages in medium supplemented with 5% (v/v) serum and 2.5 micrograms/ml
      endothelial cell growth supplement. Several of these lines express basal levels
      of ICAM-1 and MHC class I but not MHC class II. One cell line, designated SGHEC
      7, retained a number of differentiated endothelial cell functions throughout its
      lifespan. These functions include increased production of tissue plasminogen
      activator in response to histamine, thrombin, and PMA. Stability of function and
      rapid growth over 24 passages endow these cells with a number of advantages over
      primary cultures. The homogeneous cell population and consistency of response
      make them ideal for biochemical and immunological studies hereto impractical with
      primary human endothelial cells. The success of this approach may allow the
      production of functional cell lines from other vascular beds.

PMID- 1379195
TI  - Toxocara canis: monoclonal antibodies to carbohydrate epitopes of secreted (TES)
      antigens localize to different secretion-related structures in infective larvae.
AB  - The major secreted glycoproteins of Toxocara canis larvae appear to be derived
      from two specialized organs within the nematode organism. Using immunogold
      electron microscopy, we have analyzed the binding patterns of a panel of
      monoclonal antibodies (Tcn-1 to Tcn-8) reactive with Toxocara excretory-secretory
      (TES) antigens. We find, first, that the esophageal gland and lumen are strongly
      reactive with monoclonals Tcn-4, Tcn-5, and Tcn-8, and because the posterior
      portion of the gut is closed, we hypothesize that products of this gland are
      released through the oral aperture. Second, a distinct anti-TES antibody (Tcn-2)
      localizes solely to the midbody secretory column, which opens onto the cuticle at
      a secretory pore. Thus, the secretory apparatus is probably functional in this
      stage of parasite as an important source of TES products. Only one monoclonal,
      Tcn-7, can bind to both esophageal and secretory structures. In addition, another
      antibody, Tcn-3, binds both to the epicuticle and to a TES antigen, but our data
      do not directly determine whether antigens located in the cuticle are
      subsequently released. Thus there are at least two, and possibly three,
      independent sources of TES antigens within Toxocara larvae.

PMID- 1379196
TI  - Neuropeptidergic innervation of intramuscular hemangiomas.
AB  - Intramuscular hemangiomas are idiopathic lesions which are either tumoral or
      developmental in origin. A close association of abnormal blood vessels with nerve
      fibers is found and may suggest that nerves have a primary inciting role in the
      development of these lesions. In the current study, the number of nerve fibers in
      different zones around the tumors, as well as the type of neuropeptides present
      in these fibers, was quantitatively assessed by computer-assisted image analysis
      of immunohistochemical staining of histological slides. The number of nerve
      fibers as determined by positive staining by anti-protein S-100 antibodies was
      found to be elevated in the immediate vicinity of the abnormal blood vessels. The
      density of the nerve fibers rapidly declined with increasing distance from the
      hemangiomas, reaching normal values at distances of over 2 mm. Furthermore,
      hemangiomas contain a significantly higher number of calcitonin gene-related
      peptide (CGRP), substance P, and Met-enkephalin-positive fibers. The most
      significant rise in number is that of CGRP-positive fibers. This neuropeptide is
      a known mitogen, which could be responsible for the growth of the hemangiomatous
      blood vessels. Substance P is a nociceptive neurotransmitter and its presence can
      explain the pain which often accompanies even tiny intramuscular hemangiomas.

PMID- 1379197
TI  - Crossing three membranes. Channel formation by aerolysin.
AB  - Aerolysin is a channel-forming toxin responsible for the pathogenicity of
      Aeromonas hydrophila. It crosses the inner and outer membranes of the bacteria in
      separate steps and is released as a 52-kDa inactive protoxin which is activated
      by proteolytic removal of approximately 40 amino acids from the C terminus. The
      toxin binds to the erythrocyte transmembrane protein glycophorin and oligomerizes
      before inserting into the membrane, producing a voltage gated, anion selective
      channel about 1 nm in diameter. Remarkably, proaerolysin appears to be dimeric,
      whereas the oligomer is a heptamer. Using chemical modification and site-directed
      mutagenesis, we have identified some of the regions of the molecule which appear
      to be involved in secretion and in channel formation.

PMID- 1379198
TI  - Effect of epidermal growth factor on insulin-like growth factor-I (IGF-I) and IGF
      binding protein synthesis by adult rat hepatocytes.
AB  - Growth hormone has been established as a primary regulator of IGF-I gene
      expression in adults, not only in liver but also in many extrahepatic tissues. We
      considered the possibility that IGF-I production by adult rat liver could also be
      stimulated by epidermal growth factor (EGF), a peptide known to be involved in
      liver regeneration. Chromatographic analysis performed after acid treatment of
      conditioned media revealed the presence of both immunoreactive (IR) IGF-I and IGF
      binding protein (IGFBP). Both IR IGF-I and IGFBP were present in the conditioned
      medium of adult rat hepatocytes in basal conditions. The stimulation of IGF-I and
      IGFBP secretion by EGF appears to be dose-dependent with a significant increment
      already evident at 5 nM. That EGF stimulates secretion is supported by the
      finding that IGF-I and IGFBP-1 mRNA levels are increased after EGF
      supplementation. We conclude that adult rat hepatocytes spontaneously produce IGF
      I and IGFBP, and that EGF is able to increase their synthesis and secretion. This
      non-growth hormone-dependent regulation of IGF-I and IGFBP-1 production by adult
      rat hepatocytes in culture indicates an important autocrine/paracrine role for
      IGF-I, particularly during liver regeneration after extensive organ mass loss.

PMID- 1379199
TI  - Acute recruitment of prolactin-secreting cells is regulated
      posttranscriptionally.
AB  - 17 beta-estradiol (E2) stimulates the release of an activity from
      neurointermediate lobe (NIL) cells which increases the relative abundance of
      prolactin (PRL) secretors in cultures of anterior pituitary (AP) cells. In the
      present study, we sought to determine whether this NIL/E2 effect was due to
      recruitment of growth hormone (GH)-releasing cells into the PRL-secreting
      population and to define the mechanism regulating this induction of PRL
      secretors. AP cells from ovariectomized rats were cultured overnight, exposed to
      NIL/E2 treatment (or medium alone) for 3 h and then subjected to reverse
      hemolytic plaque assays for PRL and GH release. We found that exposure to NIL/E2
      increased by 10% the proportion of AP cells that secreted PRL but did not
      influence the overall abundance of cells that released GH. A more critical
      analysis of these cultures revealed that all of the newly recruited PRL-secreting
      cells also released GH. This increment in the proportion of cells that released
      both PRL and GH concurrently was accompanied by an equivalent decrease in the
      fraction that secreted GH alone. Thus, it appeared that NIL/E2 treatment
      initiated PRL secretion by cells that previously released only GH. We then tested
      whether this induction of PRL secretors required the synthesis of proteins and/or
      RNA. We found that the protein synthesis inhibitor cycloheximide completely
      abolished the recruitment of PRL-releasing cells by NIL/E2 treatment, whereas the
      RNA synthesis inhibitor actinomycin D had no effect on this response. We conclude
      that NIL/E2 treatment induces PRL secretion by cells that formerly released only
      GH and that this induction is regulated posttranscriptionally.

PMID- 1379200
TI  - Chemotactic and mitogenic activities of granulosa cells in developing follicles.
AB  - Chemotactic and mitogenic activities of granulosa cells in developing follicles
      were studied. Immature rats were subcutaneously injected with 20 IU of pregnant
      mare's serum gonadotrophin and killed at various intervals after injection. The
      ovaries were removed and granulosa cells were isolated and cultured in a serum
      free medium supplemented with insulin, transferrin and hydrocortisone.
      Chemotactic and mitogenic activities in the conditioned medium were determined.
      Our results demonstrated that in addition to mitogenic activity, chemotactic
      activity was also expressed in the conditioned medium of granulosa cells. Both
      activities increased with the maturity of follicles. A gel filtration analysis
      revealed that there were two peaks showing both mitogenic and chemotactic
      activities with a molecular size smaller than 5000. These peaks had various
      sensitivities to heat and trypsin treatment. In addition, the active component of
      both peaks was organic solvent-extractable. A thin-layer chromatography analysis
      indicated that the lipid component was not prostaglandin, estradiol or
      hydrocortisone.

PMID- 1379202
TI  - The multiple beta-tubulin genes of Xenopus: isolation and developmental
      expression of a germ-cell isotype beta-tubulin gene.
AB  - In this report, we demonstrate the presence of multiple beta-tubulin genes in
      Xenopus and begin to explore the regulation of isotypes within the beta-tubulin
      family by focusing on the characterization of a specific beta-tubulin cDNA
      derived from a Xenopus oocyte library. This clone (XLOT: Xenopus laevis oocyte
      beta-tubulin) contains the entire protein coding and 3'-untranslated regions of
      the gene, and is only missing approximately eleven nucleotides from the start of
      transcription. The XLOT transcript is ubiquitously expressed, but steady-state
      amounts are highest in immature oocytes and in testes. Consistent with the
      present understanding of this type of autoregulation, levels of oocyte beta
      tubulin transcript vary in accordance with fluctuating polymeric/monomeric
      tubulin protein ratios both in the developing oocyte and as the late stage oocyte
      matures to an unfertilized egg. In addition, steady-state levels of the oocyte
      beta-tubulin transcript do not increase as the total number of cells per embryo
      increase during embryogenesis. Although one major and three minor transcriptional
      start sites are utilized in immature oocytes and adult tissues, usage of each
      individual site varies during oogenesis and embryogenesis. The preferential
      expression in germ cells indicate that the oocyte beta-tubulin transcript may
      provide a useful marker for gonadal differentiation in early amphibian
      development.

PMID- 1379201
TI  - Regulation of adenohypophyseal messenger RNAs in female rats by age,
      hypothyroidism, estradiol and neonatal androgenization.
AB  - Hormonal regulation of adenohypophyseal messenger ribonucleic acids (mRNAs)
      encoding preprotachykinin (PPT), prolactin (PRL) and thyrotropin beta subunit
      (TSH beta) was examined in juvenile and pubertal female rats. Hypothyroidism,
      initiated on day 2 (d2) or 22 (d22) of life, increased PPT and TSH beta mRNAs but
      decreased PRL mRNA 17 days later. Exogenous estradiol given for 3 days reduced
      PPT mRNA in pubertal (d38) but not juvenile (d18) euthyroid females; conversely,
      estradiol increased PRL mRNA on d18 but not d38. In hypothyroid females however,
      estradiol decreased PPT and TSH beta mRNAs at both ages and increased PRL mRNA in
      pubertal but not juvenile females. Thus, regulation of adenohypophyseal mRNAs by
      estradiol varies with age and thyroid status. In previous studies,
      adenohypophyseal tachykinins increased in male, but not female rats at puberty.
      This sex difference was not reproduced here by neonatal androgenization of
      females, suggesting that it is not mediated by hypothalamic sexual
      differentiation. However, PRL mRNA increased in androgenized females; this
      increase was prevented by ovariectomy, suggesting its medication by estradiol.

PMID- 1379203
TI  - The expression of liver acute-phase protein genes during rat development and in
      response to inflammation of the dam.
AB  - The hepatic expression of albumin (Al) and plasma acute phase protein genes (APP)
      was examined during the development of rat liver and in response to inflammation
      of the dam. Throughout the 10- to 20-day gestation period the level of alpha 2
      macroglobulin (alpha 2M) mRNA in fetal liver exceeded twice that of the adult
      liver. The concentrations of the other APP and Al mRNAs were 10-30% of those of
      the adult liver between days 10 and 13 of gestation, then increased to values
      which ranged from 40% for haptoglobin (Hp) to 80% for Al and alpha 1-acid
      glycoprotein (AGP) mRNAs on day 19 of gestation. The transition of fetuses to an
      extrauterine environment was followed by a temporary overexpression of the Hp
      gene and an increase of the fibrinogen (Fb), AGP and thiostatin (TST) mRNAs to
      adult levels. Fetal liver responded to inflammation of the mother by a
      transcriptional induction of all of the investigated APP genes, except for the Fb
      gene whose level of expression remained unchanged. The pattern of individual APP
      genes expression in maternal and fetal livers was similar and characteristic for
      the acute phase reaction.

PMID- 1379204
TI  - Effects of several calcium channels modulators on the [3H]noradrenaline release
      and 45Ca influx in the rat vas deferens.
AB  - 1. The effects of nifedipine (1 microM), CdCl2 (0.1 mM) and the Bay K 8644
      enantiomers (1 microM) on [3H]noradrenaline release and 45Ca uptake in epididymal
      and prostatic rat vas deferens were investigated. 2. Nifedipine, CdCl2 and Bay K
      8644 optical isomers did not affect the basal tritium release. However, the
      [3H]noradrenaline release evoked by high potassium (50 mM) from both portions of
      rat vas deferens was markedly inhibited by CdCl2, scarcely affected by nifedipine
      and not modified by Bay K 8644 enantiomers. 3. (-)-Bay K 8644 increased the basal
      and potassium (50 mM) induced 45Ca uptake whereas (+)-Bay K 8644, nifedipine and
      CdCl2 did not alter the basal 45Ca uptake. However, they strongly inhibited the
      uptake induced by potassium in both portions of rat vas deferens. 4. These
      results suggest that the calcium channels (mainly L type) are involved on the
      contractions in rat vas deferens epididymal and prostatic halves; these channels
      differ from those present in sympathetic nerve terminals (likely of N Type) which
      modulates the NA release. 5. This study also shows that Bay K 8644 optical
      isomers possess opposite effects on the L channels of bisected rat vas deferens
      smooth muscle.

PMID- 1379205
TI  - Vasoconstrictive responses elicited by endothelin in bovine cerebral arteries.
AB  - 1. Endothelin (ET-1) induced concentration-dependent contractions, which were
      slowly developed in segments of bovine cerebral arteries. Furthermore, this agent
      produced tachyphylaxis. 2. The contractions evoked by ET-1 were markedly reduced
      in Ca-free medium containing 1 mM EGTA and by the Ca channel antagonist,
      nifedipine (1 microM), but increased by the Ca channel agonist, BAY K 8644 (10
      nM). 3. The contractions caused by ET-1 were significantly reduced by the protein
      kinase C (PKC) inhibitor, staurosporine (1 and 10 nM). 4. These results indicate
      that ET-1 induced potent vasoconstrictive responses, probably mediated by PKC
      activation, which were mainly dependent on extracellular Ca; this Ca enters the
      smooth muscle cells via dihydropyridine sensitive Ca channels.

PMID- 1379206
TI  - [Isolation and analysis of brain-specific sequences from cDNA libraries for
      various segments of the human brain].
AB  - The cDNA libraries in gt10 were constructed from total poly(A)+RNA of human
      forebrain cortex, cerebellar cortex and medulla oblongata. We selected the clones
      which gave hybridization signal with brain cDNA only, or gave no signal from
      these libraries. Expression pattern and structure of two brain-specific clones
      Hfb1 from forebrain library and Hmob3 from medulla oblongata library were
      analyzed in detail. Hfb1 hybridized to two different transcripts (about 5 and 2
      kb) from frontal cortex, but to a single (longest) from cerebellum. Hfb1 sequence
      includes 958 nucleotides. Comparison of Hfb1 with the Gene Bank revealed no
      homology with the sequences present in the Bank. At 3'-end there is poly(A) tail
      of 24 bases, there is the AATCAA sequence 55 nucleotides upstream which probably
      serves as a polyadenylation signal. However, AATCAA directs polyadenylation in
      vitro with very low efficiency. We found no open reading frame in the clone and
      this is in agreement with the data indicating that brain-specific RNAs has
      extremely long 3'-untranslated regions. Hmob3 was partially sequences. We
      compared its primary structure with the sequences from the Gene Bank and revealed
      no homology. Hmob3 expresses in different parts of human brain and in sceletal
      muscle but does not express in other tissues.

PMID- 1379207
TI  - [Treatment of curatively inoperable mouth cancers].

PMID- 1379208
TI  - Detection of chronic hepatitis C virus infection by four diagnostic systems:
      first-generation and second-generation enzyme-linked immunosorbent assay, second
      generation recombinant immunoblot assay and nested polymerase chain reaction
      analysis.
AB  - Serum samples from 100 patients with non-A, non-B hepatitis-related chronic liver
      disease and 100 patients with hepatitis B-related chronic liver disease were
      tested by first-generation and second-generation enzyme-linked immunosorbent
      assays, a second-generation recombinant immunoblot assay and the nested
      polymerase chain reaction. In non-A, non-B hepatitis-related chronic liver
      disease, second-generation enzyme-linked immunosorbent assay (anti-c22 and/or
      c200) and second-generation recombinant immunoblot assay showed 98% positivity,
      whereas first-generation enzyme-linked immunosorbent assay (anti-c100-3) showed
      89% positivity. The two second-generation recombinant immunoblot assay-negative
      samples were positive by nested polymerase chain reaction, but one second
      generation recombinant immunoblot assay-positive sample was polymerase chain
      reaction negative. However, when this second-generation recombinant immunoblot
      assay-positive sample was tested by polymerase chain reaction using another set
      of primers, it was polymerase chain reaction positive. Therefore, 100% of the non
      A, non-B hepatitis-related chronic liver disease serum samples were hepatitis C
      virus RNA positive by polymerase chain reaction. Nine hepatitis B-related chronic
      liver disease samples were first-generation enzyme-linked immunosorbent assay
      positive. Of the eight second-generation enzyme-linked immunosorbent assay
      positive hepatitis B-related chronic liver disease samples, six were first
      generation enzyme-linked immunosorbent assay positive and five were second
      generation recombinant immunoblot assay positive and polymerase chain reaction
      positive. One indeterminate second-generation recombinant immunoblot assay sample
      was polymerase chain reaction negative. Therefore, second-generation recombinant
      immunoblot assay appears to be as useful as polymerase chain reaction for
      detecting a chronic hepatitis C virus infection, although some discrepancies were
      noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379209
TI  - Immunohistochemical detection of hepatitis C virus-infected hepatocytes in
      chronic liver disease with monoclonal antibodies to core, envelope and NS3
      regions of the hepatitis C virus genome.
AB  - The localization of hepatitis C virus-infected hepatocytes in the human liver
      remains unclear despite the development of a serological assay for the antibody
      to hepatitis C virus. We studied their localization immunohistochemically with
      monoclonal antibodies to core, envelope and NS3 antigens of hepatitis C virus. We
      examined 48 liver biopsy samples from C100-3 antibody-positive patients with
      chronic liver disease (chronic persistent hepatitis, 5 cases; chronic active
      hepatitis, 41 cases; cirrhosis, 2 cases) and 12 liver biopsy samples from C100-3
      antibody-negative patients with chronic liver disease (type B chronic hepatitis,
      8 cases; alcoholic liver disease, 4 cases). In the C100-3 antibody-positive
      group, positive immunostaining for core antigen, envelope antigen and NS3 antigen
      was found in 23% (11 of 48), 24% (11 of 45) and 24% (11 of 46), respectively.
      Negative results were obtained in the C100-3 antibody-negative group. Hepatocytes
      with positive staining were scattered in the lobules, and they were found in the
      same regions irrespective of whether the antibody to core antigen, to envelope
      antigen or to NS3 antigen was used. Each positive cell was strongly stained in
      the cytoplasm; these decorations disappeared after absorption of the primary
      antibody with purified antigen. mean ALT levels in the patients with positive
      immunostaining for core, envelope or NS3 antigen (174.8 +/- 105.7 U/L) tended to
      be higher than in those with negative immunostaining (142.0 +/- 93.8 U/L). On
      histological evaluation of liver specimens with a scoring system of the
      histological activity index, intralobular inflammation and fibrosis had higher
      scores for samples with positive rather than negative immunostaining (p less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379210
TI  - Molecular characterization of cystic fibrosis: 16 novel mutations identified by
      analysis of the whole cystic fibrosis conductance transmembrane regulator (CFTR)
      coding regions and splice site junctions.
AB  - The spectrum of cystic fibrosis (CF) mutations was determined in 105 patients by
      using denaturing gradient gel electrophoresis to screen the entire coding regions
      and adjacent cystic fibrosis transmembrane conductance regulator (CFTR) gene
      sequences. The nucleotide substitutions detected included 16 novel mutations, 11
      previously described defects, and 11 nucleotide sequence polymorphisms. Among the
      novel mutations, 6 were of the missense type, 4 were nonsense mutations, 4 were
      frameshift defects, and 2 affected mRNA splicing. The mutations involved all the
      CFTR domains, including the R domain. Of the 61 non-delta F508 CF chromosomes
      studied, mutations were found on 36 (59%), raising the proportion of CF alleles
      characterized in our patient cohort to 88%. Given the efficacy of the screening
      method used, the remaining uncharacterized mutations probably lie in DNA
      sequences outside the regions studied, e.g., upstream-promoter sequences, the
      large introns, or putative regulatory regions. Our results further document the
      highly heterogeneous nature of CF mutations and provide the information required
      for DNA-based genetic testing.

PMID- 1379211
TI  - A new mutation (1078delT) in exon 7 of the CFTR gene in a southern French adult
      with cystic fibrosis.

PMID- 1379212
TI  - Growth characteristics and proteins of plaque-purified strains of Rickettsia
      tsutsugamushi.
AB  - Six plaque-purified strains of Rickettsia tsutsugamushi (Karp, Gilliam, Kato,
      JC472B, TA716, and TA763) that fall into three categories of virulence for mice
      were compared by several parameters. Five of the six strains formed plaques of
      identical size in mouse cells, but each of three strains tested (representing
      three mouse virulence types) had a different doubling time in mouse cell
      cultures. Neither of these properties correlated strictly with virulence in mice,
      although the avirulent TA716 strain replicated much more slowly than the more
      virulent Karp and Gilliam strains. R. tsutsugamushi strain heterogeneity was also
      manifested at the polypeptide level by migration rates in sodium dodecyl sulfate
      polyacrylamide gels of three of the major scrub typhus antigens (Sta110, Sta56,
      and Sta47), with those of Sta110 differing most widely. As expected,
      immunoblotting with polyclonal mouse sera showed substantial cross-reactivity
      among the major antigens of the six strains. Similar tests with Karp-induced
      monoclonal antibodies (MAb) demonstrated that some epitopes on Sta110 and Sta56
      were shared by fewer than the six strains, but they identified no epitope unique
      to Karp. In contrast to the ready demonstration of antigenic heterogeneity in
      Sta110 and Sta56, four of the five Sta47-specific MAb reacted well with Sta47
      from each of the six strains; the remaining MAb bound Sta47 from Karp and the
      Karp-like JC472B strain more strongly than Sta47 from the other four strains. The
      MAb also were useful in indicating the possible occurrence of Sta47 as dimers and
      trimers, the presence of Sta110 (as well as Sta56 and Sta47) in the rickettsial
      membrane, and the apparent interaction of the putative heat shock protein Sta58
      with Sta47 or Sta47-Sta56 complexes.

PMID- 1379213
TI  - Immunocytodiagnosis of atypical hyperplasia and endometrial carcinoma in post
      menopausal women.
AB  - In the present study we have evaluated whether monoclonal antibodies (MAbs) B72.3
      and AR-3 which display, on histological preparations, a differential reactivity
      with normal and transformed endometrium, could be a useful adjunct to endometrial
      cytology in the identification of pre-neoplastic and neoplastic conditions.
      Immunocytochemical (ICC) tests, using the 2 reagents, were performed on normal
      cycling endometrium and on hyperplastic and malignant lesions collected by the
      endocyte technique both from 86 surgically resected specimens and from 62
      postmenopausal symptomatic and asymptomatic outpatients. The results obtained
      showed that the combination of the 2 MAbs can complement conventional morphology
      in the identification of pre-malignant atypical lesions and endometrial carcinoma
      of unclear cytological features, thus allowing a selection of those patients who
      are candidates for fractional curettage.

PMID- 1379214
TI  - HOX gene expression in normal and neoplastic human kidney.
AB  - As a consequence of transformation, cancer cells generally lose some of their
      differentiative properties. Thus, alterations interfering with the genetic
      mechanisms required to maintain embryonic determination could lead to
      tumorigenesis. Homeobox genes are a network of genes encoding nuclear proteins
      containing DNA-binding homeodomains that are highly conserved throughout
      evolution. They are expressed in a stage-related fashion in the developing embryo
      and, in adult life, in normal tissues. In mice and humans, homeobox genes of the
      HOX family are organized in 4 clusters on different chromosomes which have
      presumably evolved by duplication of a primordial gene cluster. Strikingly, the
      order of genes within each cluster is also highly conserved throughout evolution,
      suggesting that the physical organization of HOX genes might be essential for
      their expression. Recent reports indicate that homeobox mutant mice display
      morphological abnormalities or show neoplastic alterations, and that growth
      factors can turn on homeobox genes. We have studied the expression of the
      Antennapedia-like HOX genes in normal human kidney and in renal carcinomas. The
      great majority of the HOX genes analyzed are expressed in a peculiar manner in
      normal kidney: blocks of genes, even entire HOX loci, are coordinately regulated.
      Alterations in HOX gene expression in renal carcinoma can be observed in 2 genes
      of the HOX-2 locus, HOX-2A and HOX-2E, which are actively expressed in normal
      kidney and silent in cancer biopsies. The HOX-3H gene is not expressed in normal
      kidney whereas the HOX-3H transcripts are present in renal carcinomas. Homeobox
      genes within the 4 HOX loci can be aligned on the basis of the maximal sequence
      homology of their homeodomains: this alignment defines 13 paralogous gene groups.
      In renal carcinomas, genes of group 10 (HOX-1D, 2F, 3E, 4B) display a marked
      difference in their transcript classes when compared to those of normal kidney.
      Our findings suggest an association between altered HOX gene expression and
      kidney cancer.

PMID- 1379215
TI  - Cryptosporidium parvum sporozoite staining by propidium iodide.
AB  - Modified Ziehl-Neelsen (ZN) acid-fast stain is the usual method for detection of
      Cryptosporidium oocysts in feces. Propidium iodide permitted us to stain free or
      intra-oocyst sporozoites. With the ZN method only 3-5% of the oocysts purified
      from three human and one experimentally infected lamb dichromate-preserved feces
      were stained by carbol fuchsin. These fuchsin-stained oocysts were free of intact
      sporozoites as identified by propidium iodide staining. Treatment with 10%
      formalin or 0.5% sodium hypochlorite increased the percentage of acid-fast
      stained oocysts and thus the sensitivity of acid-fast staining. Treatment with
      sodium hypochlorite induced intra-oocyst sporozoite alterations as demonstrated
      by flow cytometric analysis of the oocysts' DNA content. Propidium iodide
      staining of fixed oocysts is a simple and rapid method to visualize sporozoites
      and to assess oocyst preservation after different treatments.

PMID- 1379216
TI  - Further characterization of monoclonal antibodies to Echinococcus granulosus
      antigen 5 and antigen B.
AB  - Two monoclonal antibodies (24.14, 61A12) to Echinococcus granulosus Antigen 5 and
      two (31.15 and 39B3) to Antigen B were further characterized using modified sheep
      hydatid cyst fluid antigens (SHCF) in ELISA. None of these four monoclonals were
      directed against carbohydrate or lipid epitopes of SHCF antigens since they all
      reacted strongly with periodate or lipase-treated SHCF. On the other hand, they
      appeared to recognize SHCF determinants of protein nature as protease treatment
      of SHCF destroyed binding with the monoclonals. Anti-Antigen B monoclonals 31.15
      and 39B3 showed strong reaction with boiled SHCF and anti-Antigen 5 monoclonal
      24.14 did not. However, the second anti-Antigen 5 monoclonal 61A12 also reacted
      with boiled SHCF suggesting that some epitopes of Antigen 5 are heat stable.
      24.14 and 61A12 may recognize a similar epitope of Antigen 5 whereas 39B3 may be
      against an epitope of Antigen B different from that recognized by 31.15.

PMID- 1379217
TI  - Endothelial leukocyte adhesion molecule-1 in endotoxin-induced uveitis.
AB  - Expression of endothelial leukocyte adhesion molecule-1 (ELAM-1) on endothelial
      cells leads to the attachment of polymorphonuclear leukocytes. The sequential
      expression of ELAM-1 and major histocompatibility complex (MHC) class II antigen
      was examined in the eyes of 59 Lewis rats with endotoxin-induced uveitis (EIU)
      after the injection of Salmonella typhimurium endotoxin. The eyes were enucleated
      at 2-hr intervals. Hematoxylin and eosin-stained paraffin-embedded sections and
      immunohistochemically stained cryostat sections were graded by two masked
      observers. The MHC class II antigen was expressed on cells in the iris and
      ciliary body 4 hr after injection of endotoxin and on the corneal endothelium, 8
      hr postinjection. It was found that ELAM-1 was expressed first on cells of the
      ciliary body and iris 10 hr after the injection of endotoxin and on the corneal
      endothelium, 22 hr postinjection. Clinical and histopathologic disease developed
      16 hr postinjection. Adherence of polymorphonuclear cells to the corneal
      endothelium was observed at the time of ELAM-1 expression. In conclusion,
      expression of ELAM-1 on ocular tissue occurred in EIU and appeared to promote
      polymorphonuclear cell accumulation in the anterior segment of the eye.

PMID- 1379218
TI  - In vitro mutagenesis of HLA-B27: single and multiple amino acid substitutions at
      consensus B27 sites identify distinct monoclonal antibody-defined epitopes.
AB  - The consensus HLA-B27 sequence includes a unique constellation of amino acid
      residues along the peptide-binding cleft. To investigate the potential role of
      this region in the antigenic structure of HLA-B27, a panel of transfected cell
      lines was produced expressing 24 mutant B27 molecules with single or multiple
      substitutions within this constellation of residues. The cells were analyzed by
      flow cytometry with a panel of four anti-B27 mAb: ME1, GSP5.3, GS145.2, and
      B27M2. Previous studies have suggested that position 67 exerts a conformational
      effect on the ME1, GSP5.3, and GS145.2 epitopes. This was further supported in
      these studies by the observation that additional substitutions at the flanking
      residues 63 and 70 could reverse the disruption of these mAb epitopes by large
      residues at 67. Substitutions at positions 69-71 disrupted the binding of ME1 and
      GSP5.3, apparently by a direct effect. Individual substitutions at either of the
      two positions bearing residues unique to B27, 70 and 97, had no significant
      influence on the binding of any of the four mAb. The region of amino acid
      positions 63-71 in HLA-B27 thus appears to participate in the formation of at
      least three distinct epitopes shared by B27 and B7, identified by ME1, GSP5.3,
      and GS145.2.

PMID- 1379219
TI  - Reversion of radiosensitivity in azacytidine-treated XRS5 cells does not result
      in full radioprotection by WR-1065.
AB  - A series of cell lines were previously generated from the radiation sensitive
      Chinese hamster ovary line xrs5 after treatment with azacytidine. Six of these
      lines have been examined for their resistance to killing by 0 to 20 Gray of 60Co
      gamma rays and the amount of radioprotection afforded by treatment with the drug
      2-[(aminopropyl)amino]ethanethiol (WR-1065). As xrs5 cells have lost the ability
      to be protected by WR-1065, studies were performed to determine whether reversion
      to radio-resistance correlated with recovery of aminothiol radioprotection.
      Treatment of azacytidine-treated, radiation sensitive and resistant cells with
      four millimolar WR-1065 30 minutes prior to irradiation enhanced survival after
      exposure to gamma radiation, although the enhancement in survival was less than
      for wild type Chinese hamster ovary K1 cells. The data suggest that there is not
      an absolute linkage between recovery of gamma ray radiation resistance and
      protection by WR-1065 and other factors, such as chromatin organization, must
      play a role.

PMID- 1379220
TI  - Self-psychological approach to posttraumatic stress disorder: neurobiological
      aspects of transmuting internalization.
AB  - This essay presents the case of a young man with severe posttraumatic stress
      disorder (PTSD) in order to demonstrate how a self-psychological orientation and
      psychotherapeutic approach enables acute symptoms to be relieved, while
      concomitantly addressing vulnerability in character structure. The self
      psychological conceptualization of the psychodynamics of PTSD is discussed, along
      with a recently proposed neuropsychological theory of PTSD. After viewing the
      pertinent neurobiological research, an integration of the self-psychological
      concepts of transmuting internalization (a purported curative factor in
      psychotherapy) with neurobiological data and behavioral observations is
      presented.

PMID- 1379222
TI  - Purification of insoluble nitric oxide synthase from rat cerebellum.
AB  - Nitric oxide synthase [EC 1.14.23] from the particulate fraction of rat cerebella
      was purified and characterized. The homogenate of rat cerebella was centrifuged
      to obtain a pellet, which was washed and incubated with Triton X-100 containing
      buffer. The enzyme activity appeared in the 100,000 x g supernatant after
      incubation with the detergent. The solubilized enzyme was then purified by
      sequential affinity chromatography using adenosine 2',5'-diphosphate agarose and
      calmodulin Sepharose 4B, which gave a product that migrated as a single protein
      band on SDS/PAGE with a molecular mass of about 150 kDa. The purified enzyme
      exhibited an absolute requirement for FAD, in addition to NADPH and
      Ca2+/calmodulin. Thus, there is an insoluble nitric oxide synthase in rat
      cerebellum that has similar characteristics to the soluble type.

PMID- 1379221
TI  - Effects of recombinant canine granulocyte colony-stimulating factor on white
      blood cell production in clinically normal and neutropenic dogs.
AB  - Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was
      administered to clinically normal dogs, cyclic-hematopoietic dogs, and dogs
      undergoing autologous bone marrow transplantation, to determine whether rcG-CSF
      could be used to stimulate WBC production and function in normal and neutropenic
      dogs. To the normal dogs, rcG-CSF was administered by SC injection at rates of 1
      microgram/kg of body weight, q 12 h; 2 micrograms/kg, q 12 h; or 5 micrograms/kg,
      q 12 h. A significant dose-dependent increase in the WBC count resulted from the
      stimulation of bone marrow progenitor cells. The increased WBC count was
      characterized by mature neutrophilia and monocytosis. Neutrophil myeloperoxidase
      and phagocytic activity were normal in rcG-CSF-treated normal dogs, demonstrating
      the production of normal functional neutrophils in response to rcG-CSF treatment.
      Recombinant canine G-CSF prevented neutropenia and associated clinical signs but
      did not completely eliminate the cycling of neutrophils in cyclic-hematopoietic
      dogs when it was administered at rates of 1 microgram/kg, q 12 h, and 2.5
      micrograms/kg, q 12 h. The time to bone marrow reconstitution was not decreased
      in dogs treated with rcG-CSF at a rate of 2.5 micrograms/kg, q 12 h, for 13 days
      following autologous bone marrow transplantation. On the basis of our findings,
      we suggest that treatment with rcG-CSF is an effective way to stimulate
      myelopoiesis in dogs, but that the dose of rcG-CSF required to stimulate WBC
      production will vary depending on the cause of neutropenia. Recombinant canine G
      CSF should be useful in stimulating production and maintaining function of WBC
      for treatment of clinical diseases seen commonly in veterinary practice.

PMID- 1379223
TI  - Mapping of a linear autoantigenic epitope within the human thyroid peroxidase
      using recombinant DNA techniques.
AB  - Autoantibodies directed against the thyroid peroxidase (TPO), the thyroid
      microsomal antigen, are widely used to diagnose human autoimmune thyroid disease.
      A cloned 3.088 kb cDNA coding for the entire mature human TPO was isolated from a
      cDNA library derived from a pathological thyroid gland of a Graves' disease
      patient and used further to generate a so-called TPO epitope cDNA library in
      order to map linear autoantigenic epitopes involving a recombinant molecular
      biology approach. The TPO epitope cDNA library consisting of randomly fragmented
      cDNA sequences inserted in the expression vector pGEX-2T was expressed in
      Escherichia coli and screened with characterized anti-TPO autoantisera from
      Hashimoto's disease patients. All the sera were positively tested with a purified
      thyroid microsomal antigen fraction (TMA/TPO). Only about 1% of examined
      autoantisera were able to recognize bacterial expressed recombinant TPO
      representing sequential antigenic determinants. A corresponding autoantigenic
      epitope with 61 amino acids in length was located at the C-terminus of human TPO.

PMID- 1379224
TI  - Expression of mRNAs for alpha-fetoprotein (AFP) and albumin and incorporation of
      AFP and docosahexaenoic acid in baboon fetuses.
AB  - alpha-Fetoprotein and albumin, two members of a multigene family, reversibly bind
      fatty acids with high affinity. The origin of alpha-fetoprotein (AFP) and albumin
      present in fetal tissues other than the liver and yolk sac is a subject of
      controversy. In this work, we have searched for the presence of the albumin and
      AFP mRNA molecules in different fetal organs of the baboon (Papio cinocephalus),
      using a highly sensitive gel-blot hybridization assay with human albumin and AFP
      cDNA probes. Large amounts of albumin and AFP mRNA molecules were found in the
      fetal liver; significant quantities were also present in the gastrointestinal
      tract and in the kidney. No detectable levels were found in the other tissues
      examined (brain, skin, spleen, pancreas, muscle, heart, thymus, placenta, and
      amnion). After injection of radiolabeled AFP into pregnant baboons, all fetal
      tissues took up the protein. White adipose tissue, kidney, intestine, lung,
      liver, and cerebral cortex showed a great uptake of exogenous AFP.
      [14C]Docosahexaenoic acid (22:6, n-3), injected at the same time, was actively
      transferred from the maternal compartment across the placenta and incorporated
      into cellular lipids by all fetal tissues and particularly by liver (around 70%
      of total incorporation). The levels of [14C]docosahexaenoic acid per gram of
      tissue increased in the order: maternal blood less than placenta less than fetal
      liver, indicating a selective accumulation of this fatty acid by the fetus. These
      results indicate that intracellular AFP in non-hepatic tissues of the developing
      baboon is, for the most part, of plasma origin.

PMID- 1379225
TI  - Molecular cloning and expression of a cDNA encoding endothelial cell nitric oxide
      synthase.
AB  - Endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), is
      derived from a guanidino nitrogen of L-arginine via its metabolism by nitric
      oxide synthase (NOS). Herein, we report the molecular cloning of a cDNA encoding
      the constitutive calcium-calmodulin (Ca2+/CaM)-regulated nitric oxide synthase
      (ECNOS). A full-length ECNOS clone was isolated by screening a bovine aortic
      endothelial cell cDNA library using a fragment of rat brain NOS (bNOS) cDNA. This
      cDNA has an open reading frame of 3615 nucleotides encoding a 1205-amino acid
      protein. Membranes prepared from COS cells transfected with the ECNOS cDNA
      demonstrated NADPH- and Ca2+/CaM- dependent conversion of L-, but not D-,
      arginine to NO and citrulline that was inhibited by NG-nitro-L-arginine methyl
      ester. Comparison of the deduced amino acid sequence of ECNOS to the bNOS and
      macrophage NOS (Mac-NOS) sequences revealed 57 and 50% identity, respectively. In
      addition, ECNOS contains a unique N-myristylation consensus sequence (not shared
      by bNOS or Mac-NOS) that may explain its membrane localization.

PMID- 1379226
TI  - Metabolic turnover of methotrexate polyglutamates in lysosomes derived from S180
      cells. Definition of a two-step process limited by mediated lysosomal permeation
      of polyglutamates and activating reduced sulfhydryl compounds.
AB  - Transport and metabolic turnover of methotrexate (MTX) polyglutamates were
      examined in lysosomes derived from S180 cells. These studies extend prior work
      from this laboratory (Barrueco, J. R., and Sirotnak, F. M. (1991) J. Biol. Chem
      266, 11732-11737) which described basic properties of a facilitative transport
      system in lysosomes capable of mediating intralysosomal accumulation of MTX
      polyglutamates. In the present report, we show that the rate of turnover of MTX
      polyglutamates in lysosomes, which releases MTX in the extralysosomal space, is
      limited by the extent of mediated intralysosomal accumulation of the
      polyglutamate and reduced sulfhydryls that activate the enzyme folylpolyglutamate
      hydrolase. Evidence is presented that cysteine functions as the naturally
      occurring reduced sulfhydryl compound in lysosomes being equipotent to 2
      mercaptoethanol as an activator of folylpolyglutamate hydrolase.
      Folylpolyglutamate hydrolase in permeabilized lysosomes from S180 cells exhibited
      a low pH optimum characteristic of a lysosomal enzyme, was activated at
      concentrations of reduced sulfhydryl at 0.1 mM and above, and exhibited Km values
      in the range of 0.2-3 microM that decreased with increase in polyglutamate chain
      length. Values for Km for MTX polyglutamates of folylpolyglutamate hydrolase
      activity were 100-200-fold lower than values for Km or Ki for facilitated
      intralysosomal transport, whereas capacities for both processes were similar.
      This relationship between the kinetic properties of each process ensures
      efficient hydrolysis of MTX polyglutamates within the lysosome.

PMID- 1379227
TI  - Characterization of a gene family encoding abscisic acid- and environmental
      stress-inducible proteins of alfalfa.
AB  - The phytohormone abscisic acid (ABA) has been proposed as a common mediator
      controlling adaptive plant responses to a variety of environmental stresses,
      including water deficit, salinity, wounding, and low temperature. We have
      recently isolated three cDNAs, pUM90-1, pUM90-2, and pUM91-4, from a cDNA library
      of ABA-induced mRNAs of alfalfa. These cDNA clones exhibit a very high degree of
      sequence homology with one another and sequence similarities with certain regions
      of several stress- and ABA-inducible genes. The polypeptides encoded by these
      cDNAs are very rich in glycine (35-40%), histidine (7-15%), asparagine (8-14%),
      and tyrosine (5-10%) and have no tryptophan and proline. All of the encoded
      polypeptides contain characteristic tandem repeats comprising glycine residues
      intercepted with histidine and/or tyrosine. The RNAs corresponding to a
      representative cDNA, pUM90-1, were induced after treatment of seedlings with low
      temperature, drought, salt, and wounding stress, but not by heat; the induction
      was maximal under low temperature treatment. ABA and ABA analog rapidly induced
      the expression of these genes, whereas gibberellic acid treatment exhibited no
      induction whatsoever. These genes appear to be specifically induced in the shoot
      tissues. Analysis of ABA induction of genes corresponding to pUM90-1 in alfalfa
      seedlings of different age groups demonstrated that these genes were inducible in
      seedlings/plants of all age groups examined. Taken together these results suggest
      that these cDNA clones encode a group of proteins that are inducible by ABA and
      multiple environmental stresses and correspond to a new family of genes of
      plants, designated as ABA- and environmental stress-inducible genes.

PMID- 1379228
TI  - Poly(A)+ RNA from rabbit intestinal mucosa induces b0,+ and y+ amino acid
      transport activities in Xenopus laevis oocytes.
AB  - Injection of poly(A)+ RNA (mRNA) isolated from rabbit intestinal mucosa into
      Xenopus laevis oocytes results in an increase in sodium-independent uptake of L
      [3H]leucine, L-[35S]cystine, and L-[3H]arginine. This uptake activity is related
      to an mRNA species corresponding to the recently isolated rabbit kidney cortex
      cDNA clone rBAT (related to b0,+ amino acid transporter; Bertran, J., Werner, A.,
      Stange, G., Markovich, D., Moore, M. L., Biber, J., Testar, X., Zorzano, A.,
      Palacin, M., and Murer, H. (1992) Proc. Natl. Acad. Sci. U.S.A. 281, 717-723) and
      to a protein involved in amino acid transport via system y+. This conclusion is
      based on the following observations: 1) mRNA isolated from mucosa of duodenum,
      jejunum, and ileum, but not from colon, induces sodium-independent uptake of L
      leucine, L-cystine, and L-arginine. 2) In Northern blot analysis, mRNA isolated
      from mucosa of duodenum, jejunum, and ileum, but not from colon, hybridizes to an
      rBAT cDNA probe, with signals of 2.2-2.3 kilobases and 3.7-3.9 kilobases. 3) mRNA
      isolated from mucosa of jejunum induces sodium-independent uptake of L-leucine
      and L-cysteine which shows an inhibition pattern corresponding to system b0,+;
      the inhibition pattern of mRNA-induced uptake of L-arginine is compatible with
      the contribution of system b0,+ and y+. 4) Hybrid depletion with an rBAT
      antisense oligonucleotide greatly prevents the mRNA-dependent induction of uptake
      of L-cystine (greater than 90%) and of L-leucine (approximately 75%); it reduces
      to about 50% the induction of L-arginine uptake. 5) After separation of mRNA on a
      sucrose density gradient, the fractions resulting in expression of b0,+ transport
      activity were also those hybridizing with rBAT cDNA; induction of transport
      activity from these fractions was also sensitive to hybrid depletion. 6) The mRNA
      induced component of L-arginine uptake which is resistant to rBAT hybrid
      depletion is inhibited by L-homoserine, only in the presence of sodium; thus, it
      is related to a system y(+)-like activity.

PMID- 1379229
TI  - A lineage-specific Ca(2+)-activated K+ conductance in HL-60 cells.
AB  - Cells of the human promyelocytic cell line HL-60 can be controllably induced to
      terminally differentiate into either granulocytes or monocyte/macrophages. HL-60
      promyelocytes and terminally differentiated macrophages express a K(+)-selective
      ion channel which is activated by intracellular free Ca2+ concentrations above
      10(-7) M. Because of its voltage independence, this channel can be distinguished
      from the voltage- and Ca(2+)-activated family of outward-rectifying channels. The
      channel is selective for K+ against Na+ and is blocked by Ba2+, thus it may be
      similar to the Ca(2+)-activated K+ channel previously described in human
      macrophages. In its sensitivity to block by charybdotoxin, this channel also
      resembles a Ca(2+)-activated K+ channel of lymphocytes, which plays a role in
      activation-dependent hyperpolarization. In contrast to promyelocytes and
      macrophages, functional expression of the Ca(2+)-activated K+ channel is
      suppressed to nearly undetectable levels in granulocytes derived from HL-60 cells
      by retinoic acid-induced differentiation. These data suggest that signals which
      produce elevation of intracellular Ca2+ will hyperpolarize promyelocytes and
      differentiated macrophages by activating this conductance; however, signals which
      elevate free Ca2+ in granulocytes must act on other effectors, which may produce
      a different final influence on membrane potential.

PMID- 1379230
TI  - Platelet-derived growth factor BB-dimer suppresses the expression of macrophage
      colony-stimulating factor in human vascular smooth muscle cells.
AB  - Vascular smooth muscle cell is a major cell component involved in the process of
      atherosclerosis. In the present study, we investigated the effects of platelet
      derived growth factor (PDGF)-BB dimer on the expression of macrophage-colony
      stimulating factor (M-CSF) in vascular smooth muscle cells isolated from human
      umbilical artery. On Northern blot analysis of total RNAs isolated from smooth
      muscle cells, with human cDNA for M-CSF, a marked dose-dependent reduction of
      mRNA level was found in PDGF-BB-treated smooth muscle cells. Cellular production
      of M-CSF was estimated by immunoblot analysis of cell lysate with specific
      polyclonal antibody against recombinant human M-CSF. A concentration of 10 ng/ml
      PDGF-BB significantly reduced M-CSF mass in smooth muscle cells compared with
      that in the absence of PDGF-BB. These results suggest that PDGF-BB plays an
      important role in the cellular metabolism of vascular wall by regulating the rate
      of M-CSF production in vascular smooth muscle cells.

PMID- 1379231
TI  - Expression of the c-Harvey ras oncogene alters peptide synthesis in the
      neurosecretory cell line AtT20.
AB  - Ras proteins are enriched in neurosecretory cells suggesting that ras may play an
      important role in regulating the differentiated properties of such cells. We
      introduced the human H-ras oncogene, EJ-ras, into the model secretory cell line
      AtT20 to determine the effects of ras oncogene expression on neuropeptide
      synthesis and release. We report here that both of these processes are changed in
      ras-transfected AtT20 cells. Stimulated release of the pituitary hormone
      corticotropin is reduced, and transcription of the gene encoding its precursor,
      proopiomelanocortin, is down-regulated. At the same time, expression of other
      genes, both housekeeping and neural-specific, remain relatively unchanged. The
      alteration of proopiomelanocortin expression in AtT20 cells following ras
      oncogene transformation supports the hypothesis that ras may play a role in the
      determination of the differentiated phenotype of neurosecretory cells.

PMID- 1379233
TI  - Recognition of a tetranucleotide loop of signal recognition particle RNA by
      protein SRP19.
AB  - The interaction of protein SRP19 with the RNA component of human signal
      recognition particle (SRP) was studied by site-directed mutagenesis of the SRP
      RNA. The effects of nucleotide changes in the tetranucleotide loop (tetraloop) of
      helix 6 showed that SRP19 recognizes a tetraloop in a sequence-specific manner.
      Adenosine 149 at the third position of the tetraloop was essential for binding.
      In contrast, changes of the base at the second position had no effect. Mutations
      that disrupt or compensate individual SRP RNA helices were generated to
      investigate the importance of base pairing and to identify other binding sites.
      Considerable base pairing was essential in helix 6. Another SRP19-binding site
      was located in the distal part of helix 8. The primary sequences of the tetraloop
      binding protein SR19 and of bacterial ribosomal protein S15 are shown to be
      similar.

PMID- 1379232
TI  - The RNA polymerase II elongation complex. Factor-dependent transcription
      elongation involves nascent RNA cleavage.
AB  - Regulation of transcription elongation is an important mechanism in controlling
      eukaryotic gene expression. SII is an RNA polymerase II-binding protein that
      stimulates transcription elongation and also activates nascent transcript
      cleavage by RNA polymerase II in elongation complexes in vitro (Reines, D. (1992)
      J. Biol. Chem. 267, 3795-3800). Here we show that SII-dependent in vitro
      transcription through an arrest site in a human gene is preceded by nascent
      transcript cleavage. RNA cleavage appeared to be an obligatory step in the SII
      activation process. Recombinant SII activated cleavage while a truncated
      derivative lacking polymerase binding activity did not. Cleavage was not
      restricted to an elongation complex arrested at this particular site, showing
      that nascent RNA hydrolysis is a general property of RNA polymerase II elongation
      complexes. These data support a model whereby SII stimulates elongation via a
      ribonuclease activity of the elongation complex.

PMID- 1379234
TI  - Three genes for the human high affinity Fc receptor for IgG (Fc gamma RI) encode
      four distinct transcription products.
AB  - Three distinct but closely related classes of receptors that bind the Fc portion
      of immunoglobulin G (Fc gamma RI, -II, and -III) have been identified in humans.
      Only Fc gamma RI has high affinity for ligand and has a unique third
      extracellular domain (EC3). We have characterized three genes for human Fc gamma
      RI (A, B, and C). Each gene consists of six exons, spans 9.4 kilobase pairs, and
      localizes to chromosome 1. Although they are remarkably similar, genes B and C
      are notably different from A; in-frame stop codons are present in the EC3 domain
      of genes B and C, and deletions occur in a splice donor sequence of gene B. Four
      distinct Fc gamma RI transcripts were analyzed. One transcript, from gene A,
      would encode a transmembrane receptor with three external domains. A second
      transcript, an alternatively spliced product of gene B, would encode a two
      external domain transmembrane receptor. Two transcripts, from genes B and C, have
      stop codons in EC3 and would be predicted to generate secreted receptors.

PMID- 1379235
TI  - Cyclic AMP-dependent protein kinase type I mediates the inhibitory effects of
      3',5'-cyclic adenosine monophosphate on cell replication in human T lymphocytes.
AB  - Human T lymphocytes were used as a model system to study the expression and roles
      of cAMP-dependent protein kinase isozymes (cAKI and cAKII) in cAMP-induced
      inhibition of cell replication. Human peripheral blood T lymphocytes expressed
      mRNA for the alpha-subforms (RI alpha and RII alpha) of the regulatory subunits
      of cAKI and cAKII and for the alpha- and beta-subforms (C alpha and C beta) of
      the catalytic subunits of cAK. At the protein level, RI alpha represented
      approximately 75% of the total R subunit activity, whereas RII alpha (phospho and
      dephospho forms) accounted for the remaining 25%. RII beta was not detected at
      either the mRNA or the protein level. The RI alpha protein was mainly (greater
      than 75%) cytosolic, whereas RII alpha was almost exclusively (greater than 90%)
      particulate associated. Treatment of proliferating T lymphocytes (activated
      through the CD3 cell surface marker) with 10 different cAMP analogs demonstrated
      that all inhibited cell replication in a concentration-dependent manner. The
      potency (as measured by the concentration giving 50% inhibition, IC50) of the
      cAMP analogs ranged from 30 microM for 8-chlorophenylthio-cAMP to 1100 microM for
      8-piperidino-cAMP. A cAMP analog pair directed to activate cAKI (8
      aminohexylamino-cAMP and 8-piperidino-cAMP) synergized in the inhibition of T
      lymphocyte proliferation, whereas a cAKII-directed cAMP analog pair (8
      chlorophenylthio-cAMP and N6-benzoyl-cAMP) did not. We conclude that activation
      of cAKI is sufficient to inhibit T lymphocyte proliferation. The membrane-bound
      cAKII may mediate cAMP actions not related to cell replication.

PMID- 1379236
TI  - Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase.
AB  - N-Heparan sulfate sulfotransferase catalyzes the transfer of sulfate from 3'
      phosphoadenosine 5'-phosphosulfate to the nitrogen of glucosamine in heparan
      sulfate. The enzyme has been previously purified to apparent homogeneity from rat
      liver (Brandan, E., and Hirschberg, C. B. (1988) J. Biol. Chem. 263, 2417-2422).
      We have now cloned the rat liver enzyme using the following strategy: (a) the
      amino acid sequence was obtained from tryptic peptides of the purified protein,
      (b) mixed oligonucleotides were generated based on the sequence of the tryptic
      peptides, (c) a polymerase chain reaction fragment was obtained using mixed
      oligonucleotide interprimer amplification of cDNA, and (d) this fragment was used
      to screen rat liver lambda gt 10 and lambda ZAP libraries. Three clones were
      obtained, one of which seems to contain the complete coding sequence of the N
      heparan sulfate sulfotransferase (N-HSST). Evidence that the cDNA clone
      corresponds to the previously purified and characterized N-HSST was the
      following: (a) the predicted sequence of the N-HSST contains all of the 11
      tryptic peptides obtained from the purified protein, (b) when a cDNA containing
      the sequence coding for the N-HSST was introduced in a eukaryotic expression
      vector and transfected in COS-1 cells, the enzyme activity was expressed 9-fold
      over controls, and (c) the characteristic of the predicted protein fits with the
      purified protein in terms of molecular weight, membrane localization, and its
      being an N-linked glycoprotein. The size of the longest cDNA isolated is 4.1
      kilobases, which is in close agreement with the 4.2-kilobase size of one of the
      mRNA observed in Northern analyses. In addition, messages of 7.0 and 8.5
      kilobases were also observed, suggesting that a large portion is untranslated.
      The latter messages were the major mRNA species detected.

PMID- 1379237
TI  - Characterization of myelin basic protein thyroid hormone response element and its
      function in the context of native and heterologous promoter.
AB  - In this report we have characterized further the myelin basic protein (MBP) gene
      thyroid hormone response element (TRE) by functional and binding analysis.
      Mutation and deletion experiments revealed that this TRE, confined to the
      sequences -184 to -167 of the MBP promoter, is able to function as a classical
      regulatory element in the context of the native and a heterologous promoter. It
      is comprised of two regions, containing a motif that is highly conserved among
      other TREs: AGGACA, arranged as an inverted palindrome. Any mutation within the
      footprinted region impaired receptor binding and function. Moreover, the deletion
      of sequences outside of the receptor footprinted region (MBP-TRE-18) resulted in
      a higher triiodothyronine responsiveness and a concomitant increase in receptor
      dependent, hormone-independent repression. Results of transfection assays showed
      that both receptors alpha and beta elicit indistinguishable triiodothyronine
      responses when the MBP-TRE functions as a regulator of a heterologous promoter
      activity. However, a preferential beta receptor transactivation was observed when
      the MBP-TRE was placed in the context of its native promoter.

PMID- 1379238
TI  - Biochemical studies on the reverse transcriptase and RNase H activities from
      human immunodeficiency virus strains resistant to 3'-azido-3'-deoxythymidine.
AB  - A series of biochemical investigations to compare the DNA polymerase and RNase H
      functions of the reverse transcriptases (RTs) corresponding to azidothymidine
      (AZT)-sensitive and -resistant human immunodeficiency virus (HIV) strains are
      described. Steady-state kinetic studies with purified recombinant enzymes
      utilizing several templates and three inhibitors, 3' azido-3' deoxythymidine
      triphosphate (AZTTP), 3-amino-thymidine 5'-triphosphate, and 2',3'-didehydro
      2',3'-dideoxythymidine 5'-triphosphate, found consistent 2-4-fold differences
      between the enzymes from the two strains over a wide pH range. A strong pH
      dependence for all three inhibitors was found at pH values below 7.4 and
      suggested an ionizable group on the enzyme with a pK of about 7. The
      sensitivities of the RNase H activities of the two enzymes to AZTTP and AZTMP
      were also compared and found to be similar. The nucleotide incorporation
      fidelities of recombinant RTs corresponding to AZT-sensitive and -resistant
      clinical isolates were compared and the error specificities determined. No
      significant differences were found. Both enzymes were equally able to incorporate
      AZTTP into an elongating M13 DNA strand with concomitant chain termination.
      Purified wild-type and mutant virions from cell-culture supernatants were
      compared in "endogenous" DNA synthesis reactions, and the sensitivities of this
      activity to AZTTP were found to be similar. The contrast between the small
      differences found in this study and the high level of viral resistance in tissue
      culture presumably reflects an incomplete understanding of AZT inhibition of HIV
      in the cell.

PMID- 1379239
TI  - cDNA cloning of a novel human ubiquitin carrier protein. An antigenic domain
      specifically recognized by endemic pemphigus foliaceus autoantibodies is encoded
      in a secondary reading frame of this human epidermal transcript.
AB  - Autoantibodies from a patient suffering from endemic pemphigus foliaceus (EPF), a
      blistering skin disease, were used to screen a lambda gt11 human keratinocyte
      cDNA library. One immunoreactive cDNA clone (lambda EPF5) containing a 900-base
      pair insert was isolated and subjected to further analysis. Eight of 25 EPF sera
      were shown to react with the EPF5 fusion protein on immunoblots. The EPF5 cDNA
      insert hybridized with a 1.2-kilobase epidermal RNA transcript on a Northern
      blot. Sequence analysis revealed that lambda EPF5 contained the complete coding
      sequence for a 24-kDa polypeptide exhibiting significant sequence homology with a
      family of enzymes known as ubiquitin carrier proteins, or E2s, which are an
      essential component of the ubiquitin-protein conjugation system. The homology was
      particularly high in the core region containing the active site cysteine. The
      keratinocyte ubiquitin carrier protein expressed in bacteria, and isolated either
      intact or as a glutathione S-transferase fusion protein, exhibited the ability to
      form a thiol ester linkage with ubiquitin in a ubiquitin activating enzyme (E1)
      dependent manner, a characteristic property of ubiquitin carrier proteins. The E2
      enzyme encoded by clone EPF5 is the first member of this protein family to be
      cloned from an epidermal source. Interestingly, the EPF autoantibody-reactive
      epitope and the ubiquitin carrier protein were shown to be encoded in two
      different translational reading frames. The relevance of the cloned EPF epitope
      in the pathogenesis of this autoimmune disorder remains to be determined.

PMID- 1379240
TI  - Myosin light chain-2 luciferase transgenic mice reveal distinct regulatory
      programs for cardiac and skeletal muscle-specific expression of a single
      contractile protein gene.
AB  - To examine the relationship between the cardiac and skeletal muscle gene
      programs, the current study employs the regulatory (phosphorylatable) myosin
      light chain (MLC-2) as a model system. Northern blotting, primer extension, and
      RNase protection studies documented the high level expression of the cardiac MLC
      2 mRNA in both mouse cardiac and slow skeletal muscle (soleus). Transgenic mouse
      lines harboring a 2100- or a 250-base pair rat cardiac MLC-2 promoter/luciferase
      fusion gene were generated, demonstrating high levels of luciferase activity in
      cardiac muscle, and only background luminescence in slow skeletal muscle and non
      muscle tissues. As assessed by in situ hybridization, immunofluorescence, and
      luminescence assays of luciferase reporter activity in various regions of the
      heart, both the endogenous MLC-2 gene and the MLC-2 luciferase fusion gene were
      expressed exclusively in the ventricular compartment, with expression in the
      atrium at background levels. Point mutations within the conserved regulatory
      sites HF-1a and HF-1b significantly cripple ventricular muscle specificity, while
      mutation of the single E-box site was without effect, suggesting that ventricular
      muscle-specific expression occurs through an E-box-independent pathway. This
      study provides direct evidence that the cis regulatory sequences in the
      cardiac/slow twitch MLC-2 gene which confer cardiac and skeletal muscle-specific
      expression can be clearly segregated, suggesting that distinct regulatory
      programs may have evolved to control the tissue-specific expression of this
      single contractile protein gene in cardiac and skeletal muscle.

PMID- 1379241
TI  - Inhibition by dexamethasone of beta 3-adrenergic receptor responsiveness in 3T3
      F442A adipocytes. Evidence for a transcriptional mechanism.
AB  - Modulation of beta 3-adrenergic receptor (beta 3AR) expression by dexamethasone
      was investigated in the murine 3T3-F442A adipocytic cell line. In untreated
      cells, a major population of binding sites (62,000-114,000 sites/cell) of low
      affinity for (-)-[3H] CGP12177 and (-)-[125I]iodocyanopindolol (corresponding to
      the beta 3AR subtype) was present along with a minor population (6,500-8,000
      sites/cell) of sites of high affinity for the radioligands (corresponding to a
      mixture of the beta 1 and beta 2AR subtypes). Long-term exposure of the cells to
      250 nM dexamethasone led to a sharp decrease in beta 3AR density (less than 5,000
      sites/cell) which paralleled a diminished potency of the beta 3AR-selective
      agonists BRL37344 and CGP12177 to stimulate the production of intracellular cAMP.
      Analysis of RNA by polymerase chain reaction and nuclear run-on assays indicated
      that dexamethasone inhibited the synthesis of beta 3AR mRNA, resulting in 4-8
      fold decrease in the steady-state levels of this mRNA. The down-regulation of
      beta 3AR protein and cellular mRNA appeared to be mediated by the receptor for
      glucocorticoids as assessed by the antagonistic action of the anti-glucocorticoid
      RU38486.

PMID- 1379242
TI  - Interaction of tRNA(Lys-3) with multiple forms of human immunodeficiency virus
      reverse transcriptase.
AB  - The interaction of several forms (p51, p66, and p66/p51) of recombinant human
      immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) with a synthetic
      derivative of its cognate replication primer, tRNA(Lys-3), has been determined by
      gel-mobility shift analysis. While p66/p51 RT is proficient in tRNA binding,
      preparations of p66 and p51 display only weak binding at elevated protein:tRNA
      ratios, despite the former containing both RNA-dependent DNA polymerase and
      ribonuclease H (RNase H) activity. Gel permeation analysis of purified p66 RT
      indicate this to be predominantly monomeric, suggesting that dimerization may be
      a prerequisite for efficient tRNA binding. Prolonged incubation of a mixture of
      the 66- and 51-kDa polypeptides results in heterodimer reconstitution,
      restoration of tRNA binding, and recovery of appreciable levels of RNA-dependent
      DNA polymerase activity. Under the same conditions, both the tRNA binding and RNA
      dependent DNA polymerase activities of the 66- and 51-kDa polypeptides are
      unaffected, suggesting that they remain in the monomeric conformation.

PMID- 1379243
TI  - Dimerization and activation of the kit receptor by monovalent and bivalent
      binding of the stem cell factor.
AB  - The protooncogene c-kit encodes a tyrosine kinase receptor for the stem cell
      factor (SCF). Mutants of c-kit were shown to confer a pleiotropic defective
      phenotype and often display negative dominance in heterozygous mice. To explore
      the involvement of receptor dimerization in this genetic phenomenon, we employed
      both a human ligand, which does not recognize the murine receptor, and a rodent
      SCF, which binds to the human receptor with 100-fold reduced affinity as compared
      with human SCF. SCF binding to living cells was found to induce rapid and
      complete receptor dimerization that involved activation of the catalytic tyrosine
      kinase function. Although receptor dimerization can be attributed to the dimeric
      nature of the ligand, no dissociation of Kit dimers occurred at high excess of
      SCF, suggesting that receptor-receptor interactions are also involved in dimer
      stabilization. This was supported by in vitro formation of heterodimers between
      the human and murine Kit proteins through monovalent binding of species-specific
      human SCF. By coexpression of human and mouse Kit in murine fibroblasts, we found
      that receptor heterodimerization in living cells involved an increase in the
      affinity of human Kit for rat SCF and also an accelerated rate of receptor down
      regulation. When a human Kit mutant lacking the kinase insert domain was
      coexpressed with the murine wild-type receptor, we observed a significant
      decrease in both the activation of the intact tyrosine kinase and its coupling to
      an effector protein, namely phosphatidylinositol 3'-kinase. Our results favor a
      receptor activation model that assumes an initial step of monovalent ligand
      binding, followed by an intermediate receptor dimer bound by one arm of the
      ligand molecule. This model predicts the existence of an intrinsic receptor
      dimerization site and provides a structural basis for genetic dominance of mutant
      SCF receptors.

PMID- 1379244
TI  - Abnormal localization of cystic fibrosis transmembrane conductance regulator in
      primary cultures of cystic fibrosis airway epithelia.
AB  - Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR), a membrane glycoprotein that forms Cl- channels.
      Previous work has shown that when some CF-associated mutants of CFTR are
      expressed in heterologous cells, their glycosylation is incomplete. That
      observation led to the hypothesis that such mutants are not delivered to the
      plasma membrane where they can mediate Cl- transport. Testing this hypothesis
      requires localization of CFTR in nonrecombinant cells and a specific
      determination of whether CFTR is in the apical membrane of normal and CF
      epithelia. To test the hypothesis, we used primary cultures of airway epithelia
      grown on permeable supports because they polarize and express the CF defect in
      apical Cl- permeability. Moreover, their dysfunction contributes to disease. We
      developed a semiquantitative assay, using nonpermeabilized epithelia, an antibody
      directed against an extracellular epitope of CFTR, and large (1 microns)
      fluorescent beads which bound to secondary antibodies. We observed specific
      binding to airway epithelia from non-CF subjects, indicating that CFTR is located
      in the apical membrane. In contrast, there was no specific binding to the apical
      membrane of CF airway epithelia. These data were supported by qualitative studies
      using confocal microscopy: the most prominent immunostaining was in the apical
      region of non-CF cells and in cytoplasmic regions of CF cells. The results
      indicate that CFTR is either missing from the apical membrane of these CF cells
      or it is present at a much reduced level. The data support the proposed defective
      delivery of some CF-associated mutants to the plasma membrane and explain the
      lack of apical Cl- permeability in most CF airway epithelia.

PMID- 1379245
TI  - Repression of myogenic differentiation by aFGF, bFGF, and K-FGF is dependent on
      cellular heparan sulfate.
AB  - We have proposed a model in which fibroblast growth factor (FGF) signalling
      requires the interaction of FGF with at least two FGF receptors, a heparan
      sulfate proteoglycan (HSPG) and a tyrosine kinase. Since FGF may be a key
      mediator of skeletal muscle differentiation, we examined the synthesis of
      glycosaminoglycans in MM14 skeletal muscle myoblasts and their participation in
      FGF signalling. Proliferating and differentiated MM14 cells exhibit similar
      levels of HSPG, while differentiated cells exhibit reduced levels of chondroitin
      sulfate proteoglycans and heparan sulfate chains. HSPGs, including syndecan,
      present in proliferating cells bind bFGF, while the majority of chondroitin
      sulfate and heparan sulfate chains do not. Treatment of skeletal muscle cells
      with chlorate, a reversible inhibitor of glycosaminoglycan sulfation, was used to
      examine the requirement of sulfated proteoglycans for FGF signalling. Chlorate
      treatment reduced glycosaminoglycan sulfation by 90% and binding of FGF to high
      affinity sites by 80%. Chlorate treatment of MM14 myoblasts abrogated the
      biological activity of acidic, basic, and Kaposi's sarcoma FGFs resulting in
      terminal differentiation. Chlorate inhibition of FGF signalling was reversed by
      the simultaneous addition of sodium sulfate or heparin. Further support for a
      direct role of heparan sulfate proteoglycans in fibroblast growth factor signal
      transduction was demonstrated by the ability of heparitinase to inhibit basic FGF
      binding and biological activity. These results suggest that activation of FGF
      receptors by acidic, basic or Kaposi's sarcoma FGF requires simultaneous binding
      to a HSPG and the tyrosine kinase receptor. Skeletal muscle differentiation in
      vivo may be dependent on FGFs, FGF tyrosine kinase receptors, and HSPGs. The
      regulation of these molecules may then be expected to have important implications
      for skeletal muscle development and regeneration.

PMID- 1379246
TI  - Direct activation of second messenger pathways mimics cell adhesion molecule
      dependent neurite outgrowth.
AB  - We present evidence that direct activation of neuronal second messenger pathways
      in PC12 cells by opening voltage-dependent calcium channels mimics cell adhesion
      molecule (CAM)-induced differentiation of these cells. PC12 cells were cultured
      on monolayers of control 3T3 cells or 3T3 cells expressing transfected N-cadherin
      in the presence of KCl or a calcium channel agonist Bay K 8644. Both potassium
      depolarization and agonist-induced activation of calcium channels promoted
      substantial neurite outgrowth from PC12 cells cultured on control 3T3 monolayers
      and increased neurite outgrowth from those cultured on N-cadherin-expressing 3T3
      monolayers. The potassium-induced response could be inhibited by L- and N-type
      calcium channel antagonists and by kinase inhibitor K-252b but was unaffected by
      pertussis toxin. In contrast activators of protein kinase C did not stimulate
      neurite outgrowth, and the neurite outgrowth response induced by activation of
      protein kinase A was not inhibited by calcium channel antagonists or pertussis
      toxin. These studies support the postulate that CAM-induced neuronal
      differentiation involves a specific transmembrane signaling pathway and suggest
      that activation of this pathway after CAM binding may be more important for the
      neurite outgrowth response than CAM-dependent adhesion per se.

PMID- 1379248
TI  - Calcium alginate beads as a slow-release system for delivering angiogenic
      molecules in vivo and in vitro.
AB  - A method previously used in this laboratory for entrapment of tumor cells in
      alginate beads has been extended to provide a slow release delivery system for
      growth factors with known in vivo angiogenic activity. Protein growth factors
      were entrapped in alginate beads in amounts sufficient to cause incorporation of
      3H-thymidine by COMMA-D cells in vitro, and in vivo neovascularization when
      injected subcutaneously into Balb/c mice. Entrapment of 125I-labelled growth
      factors showed that the amount of molecule entrapped in alginate beads may vary
      with the charge of the molecule. In vitro cell proliferation studies showed that
      entrapment in alginate beads may provide a slow-release system or a stabilizing
      environment for the protein. In some cases biological activity of the growth
      factor in solution was increased by the presence of control alginate beads. When
      alginate-entrapped growth factors were injected into Balb/c mice, induction of
      new blood vessels could be monitored qualitatively by macroscopic photography and
      assessed quantitatively by measuring the pooling of radiolabelled red blood cells
      at the experimental site. Subcutaneous injection of purified angiogenic factors
      not entrapped in alginate beads did not cause neovascularization. Diffusion of
      125I-labelled growth factors from alginate beads in the animal showed that
      release in vivo may depend on the charge of the protein molecule. These results
      indicate that injection of purified molecules entrapped in alginate beads
      provides an effective localized and slow-release delivery of biologically active
      molecules. This delivery system may extend the time of effectiveness of
      biologically active molecules in vivo compared to direct injection without
      alginate entrapment. The method of entrapment and injection has potential for
      identifying active factors in tumor-induced angiogenesis and testing new
      compounds as modulators of neovascularization.

PMID- 1379247
TI  - Disulfides modulate RGD-inhibitable cell adhesive activity of thrombospondin.
AB  - Thrombospondin (TSP) contains the Arg-Gly-Asp (RGD) sequence that is thought to
      be important for cell adhesion mediated by several cell-surface integrin
      receptors. The RGD sequence is located in the type 3 repeat region of TSP that
      has multiple Ca2+ binding sites and is subject to a complex intramolecular thiol
      disulfide isomerization. TSP that we isolated from thrombin-activated human
      platelets using buffers containing 0.1 mM Ca2+, in which Cys974 is the major
      labeled cysteine, did not have RGD-inhibitable adhesive activity. However, one of
      our preparations of TSP and TSP purified following alternative procedures using
      greater than or equal to 0.3 mM Ca2+ did have RGD-inhibitable adhesive activity.
      Reduction of TSP with DTT, either before or after adsorption to surfaces,
      enhanced its adhesive activity. Reduced TSP supported robust cell spreading when
      coated at concentrations as low as 1 micrograms/ml, whereas "adhesive" TSP not
      treated with DTT was active at coating concentration of greater than 20
      micrograms/ml and supported only modest cell spreading. Lower DTT concentrations
      were required for enhancement of the adhesive activity of TSP if Ca2+ was
      chelated with EDTA. Cellular adhesion to DTT-treated TSP was inhibited by RGD
      containing peptide and by mAb to a functional site of the alpha v beta 3
      integrin. Cell blots of reduced proteolytic fragments of TSP localized the
      adhesive activity to the RGD-containing type 3 repeat region. These results
      suggest a novel mechanism for regulation of integrin-ligand interactions in which
      the ligand can isomerize between inactive and active forms.

PMID- 1379249
TI  - [Synergic effect of Dextran 70 at 32% and an antibiotic in the prevention of
      peritoneal adhesions. Experimental study in rats].
AB  - In an experimental study we evaluate the anti-adherential effect of four
      different solutions: physiological serum, Chloramphenicol, Dextran 70 (32%) and
      the association of these last two solutions. Synergic effect is shown when using
      an antibiotic (Chloramphenicol) with a non-bactericid solution (Dextran).
      Comparing our results with current literature, we are confident on the efficacity
      of similar association concerning other solutions than Dextran 70 (32%).

PMID- 1379250
TI  - Evaluation of the interaction of protein alpha-amino groups with M(II) by
      immobilized metal ion affinity chromatography.
AB  - The adsorption properties of various peptides and proteins, lacking histidyl
      groups, on immobilized Cu(II), Ni(II), Zn(II) and Co(II) ions are described; at
      pH 6 and below they were little retarded. At higher pH the retention became
      pronounced for iminodiacetate (IDA)-Cu(II) gel. This effect seems to be related
      to the presence of a terminal alpha-amino group; in the absence of this group the
      retention of the protein was largely eliminated. At pH 8.5 a terminal alpha-amino
      group is adsorbed as strongly as a histidyl group. IDA-Ni(II), IDA-Zn(II) and IDA
      Co(II) gels display little or no attraction for the terminal alpha-amino group of
      a protein.

PMID- 1379251
TI  - Purification, characterization and crystallization of recombinant HIV-1 reverse
      transcriptase.
AB  - The pol I gene from HIV-1 encoding the protease, reverse transcriptase (RT) and
      endonuclease has been expressed in Escherichia coli. By modifying the
      fermentation conditions and developing a new purification scheme, the yield of
      purified RT has been increased substantially compared with that obtained in an
      earlier procedure. The expressed RT was purified to homogeneity by ammonium
      sulphate fractionation followed by chromatography on DEAE Sepharose, Heparin
      Sepharose, S Sepharose and Poly(A)-Sepharose. The purified HIV-RT is a
      heterodimer (p66/p51) with an isoelectric point close to 8 and with a tendency to
      aggregate. The proteolytic product (p51), corresponding to the N-terminal end of
      the RT molecule, was isolated and identified, as were also some bacterial
      polypeptides that co-elute with HIV-RT during the early stages of the
      purification. The heterodimer was crystallized in several morphological forms
      using the vapour-diffusion hanging drop technique. To concentrate the protein and
      to change the buffer for crystallization, reverse-salt-gradient chromatography
      and micropreparative columns were used. The best crystals diffracted to 9 A
      resolution. The best crystals of native RT diffracted to 9 A resolution and in
      complex with nucleic acids to 4.5 A resolution (using a rotating anode X-ray
      source).

PMID- 1379252
TI  - Purification of complex protein mixtures by ion-exchange displacement
      chromatography using spacer displacers.
AB  - The anion-exchange separation of complex protein mixtures by displacement
      chromatography using spacer displacers driven by high-affinity final displacers
      is demonstrated. Guinea pig serum was separated on a medium-resolution adsorbent
      using a single heterogeneous mixture of carboxymethyldextran displacers to space
      the protein components. Mouse liver cytosol was separated on a low-resolution
      adsorbent using six carboxymethyldextran spacer displacers of increasing column
      affinity. The demonstration of the purification of alkaline phosphatase from E.
      coli periplasm by displacement chromatography on a high-performance liquid
      chromatography column is reviewed. The benefits of spacer displacers for
      separating minor components from complex biological protein mixtures is
      discussed. A simplified method for preparing carboxymethyldextran displacers is
      presented.

PMID- 1379253
TI  - Lectin affinity electrophoresis of alpha-fetoprotein. Increased specificity and
      sensitivity as a marker of hepatocellular carcinoma.
AB  - alpha-Fetoprotein (AFP) is widely used as a marker of hepatocellular carcinoma
      (HCC) for assisting diagnosis and also for screening purposes, even though its
      sensitivity has been decreased slightly as a result of the earlier detection of
      HCC by ultrasonography. Using lectin-dependent fractionation of AFP, the
      diagnostic sensitivity as well as the specificity of AFP can be increased
      compared with measurement of total AFP. Furthermore, lectin-reactive forms of
      AFP, AFP-L3 and AFP-P4, have been shown to serve as preclinical markers of HCC.
      Accordingly, AFP is still the most reliable marker of HCC in screening and
      monitoring high-risk patients.

PMID- 1379254
TI  - Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in
      multiple human tissues during fetal life and early infancy.
AB  - The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has
      been detected in many cells and tissues. In the rat, there is a dramatic
      developmental regulation of IGF-II/M6P receptor expression, the receptor being
      high in fetal and neonatal tissues and declining thereafter. We have
      systematically studied the expression of the human IGF-II/M6P receptor protein in
      tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months
      postnatal). We have asked 1) whether there is differential expression among
      different organs, and 2) whether or not the human IGF-II/M6P receptor is
      developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein
      was extracted from human tissues using a buffer containing 2% sodium dodecyl
      sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting
      using an anti-IGF-II/M6P receptor antiserum (no. 66416) and 125I-protein A or an
      immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all
      tissues studied with the highest amount of receptor being expressed in heart,
      thymus, and kidney and the lowest receptor content being measured in brain and
      muscle. The receptor content in ovary, testis, lung, and spleen was intermediate.
      The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without
      reduction of disulfide bonds) varied among the different tissues: in brain the
      receptor was of lower molecular weight than in other organs. Immunoquantitation
      experiments employing 125I-protein A and protein extracts from human kidney at
      different ages revealed a small, albeit not significant, difference of the
      receptor content between fetal and postnatal tissues: as in other species, larger
      amounts of receptor seemed to be present in fetal than in postnatal organs. In
      addition, no significant difference of the receptor content between human fetal
      liver and early postnatal liver was measured employing 125I-protein A
      immunoquantitation in three fetal and five postnatal liver tissue samples. The
      distribution of IGF-binding protein (IGEBP) species, another abundant and major
      class of IGF binding principles, was also measured in human fetal and early
      postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting
      with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was
      differential expression of the different classes of IGFBPs in the various
      organs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1379255
TI  - Role of protein kinase-C in regulation of insulin-like growth factor-binding
      protein-1 production by HepG2 cells.
AB  - Insulin-like growth factor binding protein-1 (IGFBP-1) is a liver-derived protein
      that modulates the mitogenic actions of the insulin-like growth factors (IGFs).
      IGFBP-1 production is potently inhibited by insulin both in vivo and in HepG2
      human hepatoma cells. To further define the pathways of IGFBP-1 regulation, we
      studied the effects of modulators of protein kinase-C (PKC) on HepG2 cell IGFBP-1
      production. Phorbol 12-myristate 13-acetate (PMA) stimulated IGFBP-1 production
      in a time- and dose-dependent manner, with maximal stimulation occurring at 10
      100 nmol/L. The degree of stimulation was dependent on cell density, ranging from
      about 2-fold in confluent to more than 10-fold in sparse cultures. Preincubation
      with PMA abolished the inhibitory effect of insulin, while preincubation with
      insulin did not inhibit PMA stimulation. The transient PKC activator diC8 had no
      effect, while studies with the PKC inhibitors sphinganine and H-7 were limited by
      solvent vehicle cytotoxicity. Staurosporine (STS), a potent PKC inhibitor,
      stimulated IGFBP-1 production 2- to 4-fold and augmented the stimulatory effect
      of PMA. Concanavalin-A, an inhibitor of PMA-stimulated PKC translocation and down
      regulation, inhibited the effects of PMA and STS. Our findings indicate that PKC
      is involved in the regulation of hepatic IGFBP-1 production. The effects of PMA,
      which causes rapid activation, followed by membrane translocation and down
      regulation of PKC, are similar to those of STS and are countered by Concanavalin
      A. These data suggest that PKC activity may mediate tonic inhibition of IGFBP-1
      production, while PKC downregulation stimulates the production of this regulatory
      protein.

PMID- 1379256
TI  - Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased
      GH and insulin-like growth factor-I levels in old men.
AB  - Aging is associated with decreased GH and insulin-like growth factor-I (IGF-I)
      levels and lean body mass, and increased body fat. Recombinant human GH treatment
      of old men partially reverses body composition changes. Administration of GH
      releasing hormone (GHRH) to GH-deficient children and young adults increases GH
      and IGF-I levels while preserving physiological GH release. We investigated
      whether GHRH injections restore GH and IGF-I levels in old men to the levels in
      young men. Healthy young (n = 9; 26.2 +/- 4.1 yr; mean +/- SD) and old (n = 10;
      68.0 +/- 6.2 yr) nonobese men underwent baseline blood sampling for measurements
      of IGF-I and 24-h profiles of GH release, followed by iv bolus GHRH stimulation
      tests. Old men then took, randomly, both low (0.5 mg) and high (1 mg) dose GHRH
      (1-29) sc injections twice daily for 14 days, with an intervening 14-day
      nontreatment period. The study protocol was repeated on day 14 of each treatment.
      At baseline, the mean peak duration of spontaneous GH release (P less than 0.005)
      and IGF-I levels (P less than 0.0001) were lower in the old men. GHRH treatment
      evoked dose-related increases in all parameters, with significant differences
      (vs. old basal values) in mean 24-h GH (P less than 0.001), area under peaks (P
      less than 0.001), peak amplitude (P less than 0.05), and IGF-I (P less than
      0.005) only at the high dose. After high dose treatment, there were no
      significant differences in these parameters between age groups. Peak and
      integrated responses to iv GHRH stimulation tests did not differ between young
      and old men either before or during GHRH treatment. Baseline serum levels of both
      testosterone (P less than 0.01) and phosphate (P less than 0.05) were lower in
      the older men. Phosphate levels increased (P less than 0.05) during GHRH
      treatment. GHRH treatment did not affect fasting glucose, urinary C-peptide,
      blood pressure, or chemistry and hematology profiles. Thus, short term sc
      administration of GHRH to healthy old men reverses age-related decreases in GH
      and IGF-I, suggesting that prolonged treatment could improve age-related
      alterations in body composition.

PMID- 1379257
TI  - Insulin-like growth factor-binding protein-3 proteolysis is induced after
      elective surgery.
AB  - The insulin-like growth factors (IGFs) are bound to several binding proteins
      (IGFBPs) that appear to regulate IGF transport, receptor binding, and action. The
      concentrations of these peptides are altered by catabolic conditions. To
      determine if IGF-I and IGFBP levels change after surgery, sera were obtained from
      16 patients before and after cholecystectomy. Immunoreactive IGF-I measured in
      plasma samples from which IGFBPs had been extracted did not change
      postoperatively. In contrast, IGF-I determined in unextracted samples increased
      roughly 3-fold postoperatively, presumably due to changes in IGFBPs. Two days
      postoperatively, IGFBP-3 levels, determined by ligand blot, averaged 36% of
      preoperative values, whereas levels of IGFBP-2 and a 24,000 mol wt IGFBP did not
      change significantly. Similarly, by immunoblot, intact IGFBP-3 was decreased 84.2
      +/- 20.2%, and a 31,000 mol wt IGFBP-3 fragment increased 57.5 +/- 47.4%
      postoperatively. Coincubation of postoperative, but not preoperative, sera with
      control sera resulted in a significant decrease in IGFBP-3 and production of
      proteolytic fragments. IGFBP-3 proteolytic activity in postoperative sera was
      markedly inhibited by antipain, Na-p-tosyl-L-lysine chloromethyl ketone,
      phenylmethylsulfonylfluoride, aprotinin, o-phenanthroline, and EDTA, but not by
      leupeptin or N-tosyl-L-phenylalanine chloromethyl ketone. This pattern of
      inhibition is consistent with a metal-dependent trypsin-like serine protease. We
      speculate that proteolysis of IGFBP-3 may alter tissue uptake of IGF-I and
      thereby help to counteract the catabolic state caused by surgery.

PMID- 1379258
TI  - Effects of recombinant insulin-like growth factor-I (IGF-I) and growth hormone on
      serum IGF-binding proteins in calorically restricted adults.
AB  - To determine the effects of exogenous insulin-like growth factor-I (IGF-I) and GH
      on IGF-binding proteins (IGFBP)-1, -2, and -3, six healthy nonobese adult
      volunteers underwent two 2-week periods of diet restriction (20 Cal/kg.day), and
      during the last 6 days of the first period received either IGF-I (12
      micrograms/kg.h by iv infusion over 16 h) or GH (0.05 mg/kg.day by sc injection).
      During the second 2-week study period, the alternate hormone was given. IGFBP-1
      and -2 concentrations were determined by specific RIA, and changes in IGFBP-3
      were assessed by ligand blotting. Free IGF-I concentrations were measured by size
      exclusion high pressure liquid chromatography, followed by RIA. Diet restriction
      alone did not affect either IGFBP-1 or -2 significantly. IGF-I treatment
      increased IGFBP-1 from 78 +/- 46 ng/mL (mean pretreatment) to 137 +/- 64 ng/mL (P
      less than 0.001; mean for the last 4 days of IGF-I). IGF-I also caused an
      increase in IGFBP-2 from 315 +/- 136 to 675 +/- 304 ng/mL (P less than 0.001). GH
      injections caused a modest decline in IGFBP-1 concentrations but had no effect on
      IGFBP-2 concentrations. By ligand blotting, both IGF-I and GH caused a modest
      increase in IGFBP-3 band intensity. In three subjects diet restriction alone
      caused a small decrease in IGFBP-3 hand intensity, and this was reversed by
      hormone treatment. Free IGF-I concentrations in serum were increased from 1.6% to
      4.4% of the total IGF-I during IGF-I infusions. GH injections caused a smaller
      increase in free IGF-I concentrations. The results show significant increases in
      IGFBP-1 and -2 during IGF-I infusion. The change in IGFBP-3, while significant,
      is quantitatively less than that in experimental animals that have been given IGF
      I while undergoing dietary restriction. The net effect of the changes in these
      three forms of IGFBPs is not sufficient to maintain a normal IGF-I-binding
      capacity in serum, because free IGF-I levels were increased disproportionately
      during the IGF-I infusions. Because hypoglycemia was noted in these subjects
      despite insulin suppression, these alterations in IGFBPs might have changed the
      tissue bioavailability of IGF-I and facilitated its hypoglycemic effects.

PMID- 1379259
TI  - Dihydrotestosterone accumulation in genital skin fibroblasts derived from elderly
      men with prostatic hyperplasia.
AB  - The conversion of testosterone to dihydrotestosterone (DHT) by 5 alpha-reductase
      and the interconversion between DHT and 5 alpha-Androstane-3 alpha,17 beta-diol
      (3 alpha-diol) by 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) were
      studied in fibroblasts derived from the genital skin of 15 prepubertal boys (2-10
      yr), 17 young men (20-40 yr), 13 elderly men (60-78 yr) without clinically
      evident prostatic pathology, and 17 elderly men (61-88 yr) with benign prostatic
      hyperplasia (BPH). Respective DHT formations from testosterone (5 alpha
      reduction) and 3 alpha-diol (3 alpha-HSOR oxidation) were not different among
      genital skin fibroblasts of the 4 groups. However, DHT degradation to 3 alpha
      diol (3 alpha-HSOR reduction) was significantly lower in fibroblasts from elderly
      men with BPH than in those from the prepubertal boys (P less than 0.01), the
      young men (P less than 0.01), and the elderly men without BPH (P less than 0.05).
      3 beta-HSOR reduction in fibroblasts of the BPH group was significantly lower (P
      less than 0.05) than in those of the elderly men without BPH; however, it did not
      differ from values for the prepubertal boys and the young men. (3 alpha + 3 beta)
      HSOR reduction was also significantly lower (P less than 0.05) in the BPH group
      than respective values of the three other groups. These results indicate that DHT
      accumulation may occur in genital skin fibroblasts from elderly men with BPH,
      resulting from a shift in the overall balance of androgen metabolism, which
      favors the net formation of DHT.

PMID- 1379260
TI  - Heterogeneity of serum peptides with immunoactivity detected by a
      radioimmunoassay for proinsulin-like growth factor-II E domain: description of a
      free E domain peptide in serum.
AB  - We have reported that normal human sera contain immunoactivity (IA) detected by a
      RIA directed against the first 21 amino acids of the E domain of proinsulin-like
      growth factor-II (pro-IGF-II). Marked elevations of E-21 IA were found in the
      serum of patients with nonislet cell hypoglycemia (NICTH) and patients with renal
      failure receiving chronic hemodialysis. In this paper we describe some of the
      properties of the E-21 IA of normal and abnormal sera. The E-21 IA eluted from a
      calibrated acid Sephadex G-50 column as two major peaks. In normal serum the
      first major peak had a mol wt (Mr) between 14,000-15,000, and the second peak had
      a Mr between 5,000-6,000. When E-21 IA from serum of a patient with NICTH was
      similarly studied, most of the IA was present as a Mr 11,000 peak and only a
      small amount was present as a 5,000-6,000 Mr peak. In contrast, most of the E-21
      IA present in the sera of patients on hemodialysis was present in the smaller
      molecular form, which eluted from a reverse phase column as a single component.
      This small Mr peak lacked determinants for the IGF-II monoclonal antibody
      (Amano), for pooled serum IGF-binding proteins, and for the IGF-I receptors on
      human placental membranes. We suggest that the 15- and 11-kilodalton peaks
      represent the glycated and unglycated forms of pro-IGF-II (E-21) reported by
      others. The glycated form appears to predominate in normal serum, whereas the
      nonglycated form predominates in the serum of patients with NICTH and renal
      failure. The 5,000-6,000 Mr E-21 IA probably represents a fragment of the free E
      domain of pro-IGF-II. Its size is consistent with cleavage of the free E domain
      between Arg46 and Arg47. The accumulation of this E-21 IA in renal failure is
      evidence that the kidney has a major role in the clearance of this fragment,
      which is not accomplished by the membranes used in hemodialysis.

PMID- 1379261
TI  - Localization of the growth hormone receptor, identified by immunocytochemistry,
      in second trimester human fetal tissues and in placenta throughout gestation.
AB  - Pituitary GH secretion appears largely unnecessary for the attainment of normal
      birth size in many species, including man. This is believed to be due to an
      immaturity and/or an absence of GH receptors in many fetal tissues. However, in
      vitro studies using late first trimester human fetal tissues have demonstrated
      mitogenic actions of GH on liver and stimulation of insulin biosynthesis in
      pancreas. To resolve this discrepancy, we have employed immunocytochemistry to
      identify the presence and distribution of GH receptors in various human fetal
      tissues. Fetuses of 14-16 weeks gestation were obtained after therapeutic
      abortion, tissues were fixed, and immunocytochemistry was performed using
      monoclonal antibodies against purified rat or rabbit GH receptor. The specificity
      of staining was confirmed by preabsorption of the antibodies with 1) adult rat
      liver membranes or 2) human fetal liver membranes, both of which possess specific
      GH-binding sites, or 3) human fetal skeletal muscle membranes, which do not
      specifically bind GH. Positive staining was seen in a subpopulation of liver
      parenchymal cells, in the ductal and endocrine tissue of pancreas, in the
      germinal layer of the epidermis and the deeper dermal layers of skin, and in the
      tubular epithelium of kidney. No immunopositive staining was seen in skeletal or
      cardiac muscle, epiphyseal growth plate, lung, intestine, or adrenal. Positive
      staining was present in the neuronal cell bodies of the cerebral cortex. GH
      receptor was also detectable as early as 8 weeks gestation in syncytial layers of
      the placenta and was maintained until term. Results demonstrate the presence of
      immunoreactive GH receptor/binding protein in some human fetal tissues early in
      development. In particular, these results would support a role for GH in the
      growth and function of liver and pancreas.

PMID- 1379262
TI  - The expression of human chorionic gonadotropin/luteinizing hormone receptors in
      human endometrial and myometrial blood vessels.
AB  - hCG/human LH (hLH) receptors have recently been found in human endometrial and
      myometrial cells and uterine vasculature. The present study was undertaken to
      further corroborate the immunocytochemical evidence for the presence of vascular
      receptors. Northern blot and in situ hybridization analyses have revealed that
      human uterus contains a major 4.3-kilobase and a minor 2.6-kilobase hCG/hLH
      receptor mRNA transcript and that these transcripts are present in part in
      endometrial and myometrial vascular smooth muscle cells and vascular endothelial
      cells. Immunoblot and immunocytochemical analyses have revealed that human uterus
      also contains a single immunoreactive receptor protein, and that this receptor
      protein in part is present in endometrial and myometrial vascular smooth muscle
      and vascular endothelium. The expression of receptor mRNA and/or immunoreactive
      receptor protein was higher in myometrial than in endometrial blood vessels, and
      higher in vessels of both uterine compartments from the secretory compared to
      proliferative phase, postmenopause, or pregnancy. The blood vessels in omentum,
      broad ligament, and parametrium did not immunostain for hCG/hLH receptors. A
      blood vessel seen traversing through parametrium immunostained for the receptor
      protein only after it entered the myometrium. The blood vessels in nontarget
      tissues did not immunostain, whereas those in some target tissues, but not all of
      them, immunostained for the receptor protein. In summary, the present study
      demonstrates for the first time that human endometrial and myometrial vascular
      smooth muscle and endothelium express hCG/hLH receptor mRNA and immunoreactive
      receptor protein. These findings suggest that hCG/hLH may directly regulate blood
      flow in human uterus and other target tissues. The reproductive state dependency
      of uterine vascular receptors suggests that these receptors are probably
      regulated by other reproductive hormones.

PMID- 1379263
TI  - Intrauterine progestin induces continuous insulin-like growth factor-binding
      protein-1 production in the human endometrium.
AB  - The effect of local intrauterine progestin on endometrial insulin-like growth
      factor-binding protein-1 (IGFBP-1) production was studied in 60 women using a
      levonorgestrel-releasing intrauterine device (IUD). Intrauterine progestin was a
      potent stimulator of stromal cell IGFBP-1 production, with 97% of endometrial
      specimens showing positive staining by immunohistological methods. After 5 yr or
      more of intrauterine progestin exposure, 100% (n = 20) of the tissues remained
      strongly positive for IGFBP-1. The IGFBP-1 content in endometrial tissue
      homogenates reached values as high as 10 micrograms/mg protein when measured by
      immunoradiometric assay. In contrast to the continuous endometrial IGFBP-1
      production induced by local progestin, no such effect could be found in
      endometria from subjects with sc progestin-releasing implants or copper IUDs.
      Although the levonorgestrel-releasing IUD had a striking effect on local
      endometrial IGFBP-1 production, it had no effect on serum IGFBP-1 levels. By
      Western ligand blot analysis, the domainating IGF-binding species in endometria
      exposed to intrauterine progestin was of 28K mol wt, corresponding to IGFBP-1,
      whereas no IGFBP species of 31-43K, corresponding to IGFBP-2 or IGFBP-3, were
      detected.

PMID- 1379264
TI  - Changes induced in serum protein profiles by ovarian stimulation during in-vitro
      fertilization--embryo transfer treatment: a comparison between conception and non
      conception cycles.
AB  - The profiles of plasma protein concentrations during the follicular phase in
      unstimulated women and in women undergoing ovarian stimulation for in-vitro
      fertilization--embryo transfer (IVF-ET) treatment are described. Plasma protein
      concentrations are correlated with those of total oestradiol (protein-bound and
      free) and total progesterone. In addition, 10 conception cycles and 18 non
      conception cycles are compared in an attempt to identify predictors of successful
      treatment. Ovarian stimulation caused a significant increase in follicular phase
      in serum concentrations of sex hormone binding globulin (SHBG), cortisol binding
      protein (CBP) and insulin-like growth factor binding protein 1 (IGFBP1). In
      contrast no increase was observed in unstimulated cycles. Serum levels of
      endometrial protein PP14 decreased significantly during the follicular phase in
      both stimulated and unstimulated cycles. Levels of pregnancy zone protein (PZP)
      were more than doubled at the time of oocyte aspiration compared to the
      unstimulated cycles. Albumin concentrations were unchanged by the stimulation.
      Throughout the follicular phase, levels of SHBG were significantly higher, and
      total oestradiol significantly lower in women who became pregnant, than in those
      who did not. Therefore, a low concentration of free, biologically active
      oestradiol seemed to favour pregnancy, as the concentration of albumin is similar
      in the two groups. The endometrial protein PP14 was significantly lower during
      the follicular phase in conception than in non-conceptional cycles. On day 2 of
      the treatment cycle, the PP14 concentration showed a 75% correct prediction of
      conception and non-conception cycles. These results suggest that levels of PP14
      may predict successful IVF cycles even before hormonal treatment is commenced.

PMID- 1379265
TI  - The acrosome reaction-inducing activity of individual human follicular fluid
      samples is highly variable and is related to the steroid content.
AB  - In this study, we have evaluated the relationship between the acrosome reaction
      inducing activity of individual human follicular fluid samples and their steroid
      content. Eighteen samples of follicular fluid were obtained during egg retrieval
      in six patients undergoing assisted fertilization. Motile spermatozoa were
      incubated in modified Tyrode's medium (26 mg/ml bovine serum albumin) for 20 h at
      1 x 10(7) cells/ml. In a single experiment, aliquots of a semen specimen were
      simultaneously treated with an aliquot of each follicular fluid sample. The
      percentage of acrosome reacted spermatozoa was determined using fluorescein
      isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) lectin. The fluids
      were also analysed by radioimmunoassay to determine the levels of progesterone,
      17 alpha-hydroxy-progesterone, testosterone and oestradiol. The results showed
      that there was a positive, highly significant correlation between the acrosome
      reaction-inducing activity and the progesterone level of each follicular fluid
      sample (r = 0.72, P less than 0.005). Additionally, treatment of the follicular
      fluid samples with charcoal-dextran caused both a decrease in progesterone
      concentration and the total loss of the acrosome reaction-inducing activity. The
      addition of progesterone restored the acrosome reaction-inducing ability in 88%
      of samples. These data support the idea that progesterone in follicular fluid is
      the molecule responsible for inducing the acrosome reaction in human spermatozoa.

PMID- 1379266
TI  - The expression of retinoic acid receptors in cultured human endometrial stromal
      cells and effects of retinoic acid.
AB  - Patterns of expression of retinoic acid receptors (RAR) in cultures of human
      endometrial stromal cells are described. Transcripts for all three classes of RAR
      were expressed in these cells but RAR-beta was expressed at a low level by
      comparison with RAR-alpha and RAR-gamma. The abundance of RAR-beta transcripts
      was elevated by treating the cells with retinoic acid, but there was no effect on
      the level of expression of RAR-alpha and RAR-gamma. The induction of RAR-beta by
      retinoic acid was detectable within 4 h and at low concentrations of retinoic
      acid (10(-10) M). Adenosine 3':5'-cyclic monophosphate (cAMP) analogues and
      forskolin, an adenylate cyclase activator, had no effect on the retinoic acid
      mediated induction of RAR-beta, contrary to recent observations on embryonal
      carcinoma cells. However, the phosphodiesterase inhibitor, 3-isobutyl-1-methyl
      xanthine (IBMX), forskolin and 8-bromo-cAMP depressed basal levels of RAR-beta
      expression. These data suggest that endometrial stromal cells may be a target
      tissue of retinoic acid in vivo, and imply a role for retinoic acid in the
      cyclical differentiation of human endometrium.

PMID- 1379267
TI  - The value of serum levels of oestradiol, progesterone and beta-human chorionic
      gonadotrophin in the prediction of early pregnancy loss.
AB  - Serial serum levels of oestradiol, progesterone and the beta-subunit of human
      chorionic gonadotrophin (beta-HCG) had been performed in 674 cycles in women
      conceiving a singleton pregnancy, either spontaneously or as a result of assisted
      conception. To determine the value of these estimations in the prediction of
      early pregnancy loss, frequency distribution curves and receiver operating
      characteristic curves were derived for the respective hormones measured at weeks
      4-7 of gestation and expressed as multiples of the median (MoM) values in
      pregnancies occurring both with and without ovarian stimulation. A cut-off level
      of beta-HCG less than 0.5 MoM gave a sensitivity of 68% with an odds ratio of 4.0
      at 7 weeks in unstimulated cycles in the prediction of pregnancy failure. A cut
      off of 0.8 MoM for progesterone gave a sensitivity of 59% and an odds ratio of
      2.8. Prospective hormonal monitoring during the early weeks of gestation may be
      useful in the prediction of early pregnancy loss and should help to avoid the
      emergency presentation of some of the complications of early pregnancy, in
      particular ectopic pregnancy. The limitations imposed by multiple pregnancies and
      uncertain gestation due to menstrual data may restrict the use of this strategy
      to specialist fertility centres.

PMID- 1379268
TI  - Improved sensitivity and specificity of a single measurement of serum
      progesterone over serial quantitative beta-human chorionic gonadotrophin in
      screening for ectopic pregnancy.
AB  - The sensitivity and specificity of a single serum progesterone measurement was
      compared against two beta-human chorionic gonadotrophin (HCG) measurements 48 h
      apart in screening for abnormal pregnancy, i.e. ectopic pregnancy, completed or
      incomplete abortion. Of 1120 patients in the first trimester presenting with a
      positive urinary pregnancy test, 116/1120 (10.4%) had an ectopic pregnancy,
      755/1120 (67.4%) had ultrasonographically confirmed intra-uterine pregnancies,
      and 249/1120 (22.2%) had abnormal intra-uterine pregnancies documented as
      complete, incomplete or missed abortions. Of the ectopic pregnancies, 113/116
      (97.4%) had a serum progesterone level less than 25 ng/ml while 516/755 (68.3%)
      viable intra-uterine pregnancies had a serum progesterone level greater than or
      equal to ng/ml. Of the 1120 patients screened, 402 (35.9%) had both a serum
      progesterone and two HCG measurements and were eligible for inclusion in this
      study. Setting a cut-off of 25 ng/ml, the sensitivity and specificity of a single
      serum progesterone measurement was then compared against two serial HCG
      measurements, utilizing receiver operating characteristic curves. This analysis
      demonstrated that a single serum progesterone measurement was significantly more
      sensitive (P less than 0.05) than two HCG measurements in screening for an
      abnormal pregnancy. In some patients, a single serum progesterone makes possible
      the diagnosis of ectopic pregnancy 2 days earlier than two HCG determinations
      because a second blood sample was not required. We conclude that a single serum
      progesterone measurement should be added to serial HCG determinations as a
      standard diagnostic screening test for ectopic pregnancy.

PMID- 1379269
TI  - Pyramid power is here to stay: behind the new food guide.

PMID- 1379270
TI  - Computer-aided analysis of DNA curves on transverse gradient gels.
AB  - Transverse pore gradient polyacrylamide gel electrophoresis of DNA restriction
      fragments was used to generate gel patterns describing migration distance as a
      function of gel concentration (Ferguson curves). These Ferguson curves were
      digitized, traced and analyzed with the aid of a personal computer. The traced
      curves were plotted semi-logarithmically and the plots were subjected to least
      squares linear regression analysis to yield values of the slope (KR) and the
      intercept at %T = 0 (YO). These values are highly precise since they are based on
      approx. 100 measurements per curve. The computerized method reduces the errors
      due to manual measurements of migration distances and is time and labor saving.
      The method is still limited to intra-experimental comparison of Ferguson curves,
      since it does not as yet comprise a determination of gel concentration. At
      present, curve tracing remains semi-automated, requiring manual intervention when
      Ferguson curves cross or approach one another. Potentially, the importance of the
      computerized analysis of transverse pore gradient gels lies in the rapid
      quantitative interpretation of Ferguson curves for detection of anomalously
      migrating DNA species. Potentially, that application provides a more sensitive
      and informative mode of detection than either the mere visual observation of
      crossing Ferguson curves or of a shift in mobility at a single gel concentration.

PMID- 1379271
TI  - Staining of argininosuccinate lyase activity in polyacrylamide gel.
AB  - A procedure for the direct staining of argininosuccinate lyase activity in
      polyacrylamide gel is described. The method was based on coupling one of the
      enzymatic products fumarate with fumarase and malic enzyme catalyzed reactions.
      Fumarate was first converted to L-malate by fumarase. Malic enzyme then catalyzed
      the oxidative decarboxylation of L-malate to give CO2 and pyruvate with
      concomitant reduction of NADP+ to NADPH. Finally the reducing power of NADPH was
      coupled to phenazine methosulfate and in turn to nitroblue tetrazolium yielding a
      deeply colored insoluble formazan which may be quantitized or semiquantitized by
      densitometer.

PMID- 1379272
TI  - [Orbital myositis, recurrence of Whipple's disease].
AB  - Whipple's disease, a chronic systemic and multi-organ disease can be associated
      with ophthalmological manifestations with or without CNS involvement. Myositis
      rarely occurs during Whipple's disease. Antibiotic treatment prevents CNS
      recurrence. We report here the association of an orbital pseudotumor with
      Whipple's disease. This myositis was discovered on a follow-up CT examination. It
      appeared only one year after the end of a long course of antibiotic treatment,
      but it resolved within a few weeks when treatment was reintroduced. Relations
      between these two diseases are discussed.

PMID- 1379273
TI  - Effect of the organophosphorous insecticide, chlorpyrifos (Dursban), on growth,
      fecundity and mortality of Biomphalaria alexandrina and on the production of
      Schistosoma mansoni cercariae in the snail.
AB  - Exposure of Biomphalaria alexandrina to sublethal concentrations (0.125, 0.25 and
      0.05 ppm) of the organophosphorous insecticide, chlorpyrifos (Dursban), induced a
      reduction in egg production and egg hatchability. Exposure of Schistosoma mansoni
      miracidia to the insecticide (60 min, 0.50 ppm) prior to infection of B.
      alexandrina did not affect the subsequent production of cercariae. However,
      exposure of S. mansoni-infected snails to the insecticide until day 55, from day
      20 to day 62 and from day 35 to 62 following infection resulted in blockage of
      cercarial shedding. Cercarial shedding commenced in some snails when the
      treatment stopped. Exposure to the insecticide in concentrations of 0.125 and
      0.25 ppm during the first 20 days following infection did not affect the
      subsequent production of cercariae, but exposure to 0.5 ppm during the first 20
      days affected markedly the production of cercariae due to a high snail mortality.
      The findings indicate that the cercaria is the target stage for the activity of
      chlorpyrifos on the intramolluscan larval development. It is suggested that S.
      mansoni cercarial production in B. alexandrina may be a useful system for
      monitoring the effect of low concentrations of pesticides on the aquatic
      environment, and that the ability by chemical means to interrupt the cercarial
      production might be a useful tool in further analyses of important aspects of the
      snail/parasite relationship.

PMID- 1379274
TI  - Pseudomonas cepacia pulmonary infection in adults with cystic fibrosis: is
      nosocomial acquisition occurring?
AB  - Ribotyping of 25 isolates of Pseudomonas cepacia taken from the sputum of 21
      adults with cystic fibrosis (CF) who were registered at the Royal Brompton
      Hospital between 1987 and 1991, revealed that seven patients (33.3%) shared
      strains of a similar ribotype pattern with others, while 14 patients (63.7%)
      harboured strains unique to each individual. Constancy of sputum strain carriage
      was seen in two of three patients sampled twice over a 3-month period. Although
      no evidence for patient-to-patient transmission of P. cepacia within this group
      of patients was found, the fact that one third of CF patients shared strains of
      the same ribotype with others, suggests that nosocomial acquisition of this
      organism may have occurred.

PMID- 1379275
TI  - Generation of monoclonal antibodies to human lymphocyte cell surface antigens
      using insect cells expressing recombinant proteins.
AB  - We have expressed human CD40 and human B7 in insect cells using the baculovirus
      expression system and have used these insect cells to immunize mice for the
      generation of monoclonal antibodies. We demonstrate here that specific monoclonal
      antibodies to human CD40 and human B7 were obtained using this approach. One
      significant advantage of this method is that immunizing mice with insect cells
      did not evoke an immune response to human cells and, therefore, EBV-transformed
      human B cells could be used to screen for specific antibody production by the
      hybridoma clones.

PMID- 1379276
TI  - Agonistic properties of anti-B cell antibodies purified on staphylococcal protein
      A may be due to contaminating protein A.
AB  - Some antibodies directed to cell surface receptors may mimic the physiological
      ligands by inducing the transmission of activation or growth signals. Such
      agonistic antibodies have proven very useful when studying functional properties
      of various receptor molecules on, e.g., lymphoid cells. However, while
      investigating the agonistic effects on tonsillar B cells of the anti-CD43
      monoclonal antibody (mAb) D4B11 and the anti-CD40 mAb S2C6, we made some
      observations which emphasize the need for caution when using antibodies purified
      by protein A affinity chromatography. Both antibody preparations were found to
      elicit changes in the intracellular free calcium concentration ([Ca2+]i) as well
      as promoting proliferation of phorbol ester activated cells. However, a closer
      analysis showed that the increase in [Ca2+]i could be attributed to soluble
      staphylococcal protein A (SpA) desorbed during antibody purification. By using
      pure soluble SpA, we were able to show that nanogram amounts were sufficient to
      increase [Ca2+]i by a mechanism that involved both a mobilization from
      intracellular stores and an influx across the B cell membrane. A similar effect
      on cytosolic Ca2+ in B cells was also noted for streptococcal protein G (protein
      G), another bacterial component used for antibody purification. However, in
      contrast to SpA, protein G had little effect on cell proliferation. These
      observations suggest that the presence of trace amounts of SpA or protein G in
      antibodies purified on these bacterial components may lead to incorrect
      interpretations of the agonistic properties of such antibodies. When the above
      findings were taken into account, it was found that the CD43 mAb D4B11, like the
      CD40 mAb S2C6, stimulated growth of B cells without causing any measurable
      increase in [Ca2+]i. Both CD40 and CD43 may thus be coupled to signalling
      pathways which do not involve breakdown of membrane phosphoinositides.

PMID- 1379277
TI  - Determination of monoclonal antibody specificity by immunoadsorption and western
      blotting.
AB  - A rapid and simple method has been developed for identifying the specificity of
      monoclonal antibodies at an early stage in the production of hybridomas. The
      technique is a micro-method utilizing biotinylated crude antigen and the surface
      of microtiter plates as an immunoaffinity matrix. The monoclonal antibodies to be
      tested are adsorbed to the microtiter wells and incubated with the labeled
      antigen preparation. Non-specific binding can be reduced by blocking and repeated
      washing steps. The specific antigen is then eluted by SDS-containing buffers,
      subjected to SDS-PAGE, blotted onto nitrocellulose and detected by enzyme-labeled
      avidin in a Western blot assay. The amount of bound and removed antigen can be
      quantitated by developing eluted and non-eluted control wells by ELISA
      techniques. Since this ELISA can be performed rapidly, only samples which contain
      sufficient specific material can be selected for electrophoresis and blotting.
      The major advantages of the technique are (i) the use of a non-radioactive label
      resulting in an easy and time-saving procedure, (ii) the possibility of
      quantitating the amount of captured and detached antigen by ELISA, (iii) the need
      for only a minimal amount of antigen, (iv) the use of unpurified antibodies of
      all isotypes, (v) a high signal-to-noise ratio, and (vi) as with all
      immunoprecipitation techniques, the possibility of detecting SDS-sensitive
      epitopes and of using crude antigen preparations. Using this method we were able
      to characterize monoclonal antibodies against both soluble proteins (mouse and
      human C1q) and membrane determinants (human pan T cell CD5 and CD7).

PMID- 1379278
TI  - Production of monoclonal antibodies against the human anaphylatoxin C5a des Arg
      and their application in the neoepitope-specific sandwich-ELISA for the
      quantification of C5a des Arg in plasma.
AB  - A panel of ten murine monoclonal antibodies (MAbs) was raised against the human
      anaphylatoxin C5a des Arg. The MAbs were shown to abrogate or significantly
      inhibit the chemotactic activity in zymosan activated serum. MAb 4A2E10E2 and MAb
      3G3C4 were used as capture and detecting antibody, respectively, in a sandwich
      enzyme-linked immunosorbent assay (ELISA) for the quantification of C5a des Arg.
      This ELISA was shown to be very sensitive (detection limit 20 pg/ml) and could be
      applied directly to plasma/serum samples. The lack of interference by plasma
      components, in particular C5, suggested specificity for an epitope on C5a (des
      Arg) which is concealed in native C5 and exposed on the activation fragment only,
      i.e., a 'neoepitope'. The mean C5a des Arg level in EDTA-plasma from 25 healthy
      individuals assessed at a 1/20 dilution was 11.2 ng/ml (SD 3.4; range 6.4-16.8
      ng/ml). The applicability of the assay was investigated in patients treated with
      haemodialysis using different membranes. Markedly elevated plasma levels of C5a
      des Arg were found in blood returning from the dialyzer following contact with
      cuprophane membranes.

PMID- 1379279
TI  - Increased ELISA sensitivity using a modified method for conjugating horseradish
      peroxidase to monoclonal antibodies.
AB  - We investigated the importance of monoclonal antibody (MCA) purity and the input
      molar ratio of horseradish peroxidase (HRPO)/IgG used for MCA conjugation on
      various immunoenzymometric assay (IEMA) parameters. The sensitivity of IEMAs for
      human follicle stimulating hormone (hFSH), human chorionic gonadotropin (hCG) and
      the free alpha subunit of hCG (hCG alpha) could be increased up to 6-fold,
      whereas non-specific binding remained within tolerable limits (E less than 0.1),
      when MCAs purified by high performance liquid chromatography (HPLC) using a
      hydroxylapatite column (HPHT) were conjugated with an input molar HRPO/IgG ratio
      of four instead of the usual ratio of two.

PMID- 1379280
TI  - Collected papers on endogenous interferon deficiencies. Special issue dedicated
      to Professor Ferdinando Dianzani.

PMID- 1379281
TI  - Interferon treatments: how to use an endogenous system as a therapeutic agent.

PMID- 1379282
TI  - Role of endogenous interferon in the high sensitivity of C3H/10T1/2 cells to the
      antiviral activity of interferon.
AB  - Addition of anti-mouse interferon (IFN) serum to untransformed 10T1/2 cells at
      the time of virus challenge led to a reduction of the IFN titers as determined by
      inhibition of CPE. The titers were reduced to values comparable to those usually
      observed for transformed 10T1/2 cells. In contrast, no change in IFN titers was
      observed when anti-IFN serum was added to transformed 10T1/2 cells. There was no
      significant difference between the two types of cells in the level of IFN induced
      by the challenge virus, VSV. The IFN level was low and did not increase after
      pretreatment of the cells with IFN. The distinct effect exerted by anti-IFN serum
      on untransformed and x-ray transformed 10T1/2 cells was not unique and comparable
      results were obtained in several other normal and transformed cells.

PMID- 1379283
TI  - The interferon system in patients with malignant disease.
AB  - Since the interferon (IFN) system involves both IFN producing and IFN responding
      cells, it is possible to study separately these phenomena, relating them to
      disease entities as well as to response to therapy. Numerous studies in animals
      and man suggest effectiveness of IFN and IFN inducer therapy in cancer. However,
      the competency of the various components of the endogenous IFN system in
      malignancy has received little attention. These studies show that in malignancy
      there may be (1) a high incidence of elevated blood levels of IFN; (2) a
      deficient response of peripheral blood mononuclear cells to endogenous and
      exogenous IFN; and (3) increased uninduced in vitro IFN production by these
      cells. These findings indicate that cancer patients are equipped with the ability
      to produce IFN and suggest that it may be the deficient response of their cells
      to IFN that plays a role in the development and progression of the disease.
      Furthermore, the finding of increased spontaneous "uninduced" production of IFN
      by cells from cancer patients suggests the possibility of an intracellular
      inducer such as found in persistently virus-infected cells.

PMID- 1379284
TI  - Suppression of macrophage Ia antigen expression by endogenous interferon
      alpha/beta.
AB  - Exogenous interferon-alpha (IFN-alpha) and interferon-beta (IFN-beta) (type I
      IFNs) are known to suppress the IFN-gamma-dependent expression of class II MHC
      (Ia) antigens on macrophages (M phi). We report here that the endogenous type I
      IFNs produced by M phi in response to IFN inducers regulate Ia expression of the
      M phi themselves. Coculture of M phi with IFN-gamma and polyinosinic
      polycytidylic acid [poly(I):poly(C)] resulted in the reduction of Ia expression
      in comparison with those cultured without poly(I):poly(C). Pretreatment of M phi
      with poly(I):poly(C) or a bacterial lipopolysaccharide (LPS), which is also a
      potent IFN inducer, in vitro or in vivo, before being exposed to IFN-gamma was
      also effective in suppressing the Ia expression. Such suppression was abolished
      by the addition of anti-IFN-alpha/beta antibodies to the M phi culture along with
      IFN-gamma. M phi cultured with L-cell conditioned medium (LCM) containing M-CSF
      were less capable of expressing Ia antigens than those cultured without LCM. The
      Ia-expressing ability of LCM-treated M phi was also restored by the addition of
      anti-IFN-alpha/beta antibodies. M phi in the early stage of sterile inflammation
      were less responsive to IFN-gamma than those in the late stage. These results
      suggest that endogenous type I IFNs, which are produced in response to natural or
      synthetic IFN-inducers, regulate M phi Ia expression in an autocrinal manner.

PMID- 1379285
TI  - Decreased interferon response by lymphocytes from children with chronic
      hepatitis.
AB  - Since a decreased interferon response has been linked with certain chronic viral
      infections, a preliminary study was undertaken to determine whether an altered
      interferon response may be involved in the pathogenesis of chronic hepatitis, a
      complication of type B hepatitis. The production of interferon by lymphocytes
      from patients with chronic hepatitis was compared with the production by
      lymphocytes from normal subjects. The amount of interferon produced by
      paramyxovirus-stimulated lymphocytes from 16 patients was substantially smaller
      than that produced by lymphocytes from 12 healthy donors. The results indicate
      that decreased production of interferon may be responsible for the chronicity of
      the disease. However, further studies are necessary to establish causality.

PMID- 1379287
TI  - Cell cycle regulation (G1) by autocrine interferon and dissociation between
      autocrine interferon and 2',5'-oligoadenylate synthetase expression.
AB  - In tertiary MEF undergoing cell cycle progression, autocrine interferon (IFN) is
      released and constitutive levels of 2',5'-oligoadenylate (2-5A) synthetase
      activity, low through the cell cycle, surge into a peak within S phase. Treatment
      of MEF with the autocrine IFN they produce elicits a 2-5A synthetase response
      from cells positioned in G0 but not from cells in G1 and from cells in S phase.
      Neutralization of the autocrine IFN by antibody shortens the length of G1 leaving
      unaltered the kinetics of progression through S and G2 and has no effect on the S
      phase-linked expression of 2-5A synthetase activity. The growth controlling
      effect of the autocrine IFN has been mapped to the second part of G1.

PMID- 1379286
TI  - Interferon production in severe hemophiliacs with and without HIV antibodies.
AB  - The interferon (IFN) system, both serum IFN levels and the in vitro IFN
      production, was investigated in 38 clinically asymptomatic multitransfused
      hemophiliacs, half positive and half negative for HIV antibodies. In most
      patients, no circulating IFN was detected; similar levels of IFN-alpha were
      obtained after peripheral blood mononuclear cell (PBMC) stimulation with Sendai
      virus both in hemophiliacs and controls, while production of IFN-gamma following
      stimulation with phytohemagglutin (PHA) was diminished in a large number of
      patients irrespective of their HIV serology. These data indicate that the
      deficiency in IFN-gamma generation is not only related to HIV contamination but
      may be a direct consequence of the chronic antigenic stimulation through Factor
      VIII concentrates.

PMID- 1379288
TI  - Deficiency in interferon production of peripheral blood leukocytes from patients
      with non-Hodgkin lymphoma.
AB  - In search for a rationale for the use of interferons (IFNs) in treatment of non
      Hodgkin lymphoma (NHL), we have investigated the IFN system of 13 patients with
      low-grade NHL, 15 patients with high-grade NHL, and 20 patients with chronic
      lymphocytic leukemia or leukemic immunocytoma (CLL/IC). Production of IFN induced
      by phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM),
      Corynebacterium parvum, Herpes simplex virus (HSV), Newcastle disease virus
      (NDV), and interleukin 2 (IL-2) were studied in the peripheral leukocytes from
      the patients and from 21 control persons by means of a whole blood technique. All
      three groups of patients with NHL had significantly reduced production upon
      stimulation by NDV (p ranged between 0.0038 and less than 0.0001) compared to
      controls. Similarly, C. parvum also induced lower titers of IFN in the leukocytes
      of patients with non-leukemic NHL (p = 0.0015 for low-grade NHL and p = 0.0038
      for high-grade NHL). When stimulated by PHA, the IFN response of all groups of
      patients was within normal range. With the exception in low-grade NHL, Con A also
      induced normal titers of IFN in the patients with NHL. The levels of IFN induced
      by PWM, HSV, and IL-2 were very low and no differences between controls and
      patients could be found. As NDV and C. parvum induce mainly IFN-alpha and the
      mitogens PHA and Con A mainly IFN-gamma, our results suggest that there is a
      deficiency in the IFN-alpha response in the patients with NHL but normal response
      in IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379289
TI  - Depressed interferon synthesis in skin fibroblasts from lung cancer patients.
AB  - Skin fibroblast cell cultures, derived from male adult lung cancer patients, an
      adult control population, and a newborn population were examined for their
      susceptibility to transformation with Kirsten murine sarcoma virus and their
      ability to respond to an interferon inducer (poly I.poly C). An association
      between sensitivity to viral transformation and induction of interferon was
      observed. Cultures derived from lung cancer patients demonstrated an increased
      sensitivity to virus transformation and a decreased ability to respond to
      interferon induction as compared with age-matched controls and newborns.

PMID- 1379290
TI  - A comparison of interferon responses to poly ICLC in males and females.
AB  - Interferon (IFN) responses to polyriboinosinic acid polyribocytidylic acid in
      poly-L-lysine and carboxymethylcellulose (poly ICLC) have been studied in detail
      in 6 men and 3 women as part of a preliminary trial in patients with multiple
      sclerosis (MS). Patients received intravenous (i.v.) doses of 100 micrograms/kg
      poly ICLC, and serum IFN levels were determined serially every 4 h for 16 h. Men
      and women produced substantial levels of IFN at 8, 12, and 16 h after infusion,
      but levels in men were consistently and significantly higher (p less than 0.05).
      Interferon responses were examined also in 3 male and 3 female Rhesus monkeys.
      Serum samples were obtained 8 and 24 h after i.v. injections of 1 mg/kg of poly
      ICLC. Again, there were significantly higher levels of IFN in males. The observed
      differences may reflect sex-linked differences in either drug metabolism or
      specific sensitivity to IFN induction by poly ICLC. The most interesting
      possibility is that the difference is due to a more general difference in IFN
      response between males and females. Studies are currently in progress to evaluate
      these possibilities.

PMID- 1379291
TI  - Circulating interferon in cytomegalovirus infected bone-marrow-transplant
      recipients and in infants with congenital cytomegalovirus disease.
AB  - In a study concerning five CMV-infected bone-marrow-transplant recipients, five
      congenital CMV diseases and appropriate controls, presence of high levels of
      circulating interferon (IFN) was demonstrated exclusively during the course of
      CMV disease. This interferon was predominantly "immune" or gamma interferon
      (gamma-IFN). These results suggest that during CMV disease the interferon
      compartment of the immune response is modified.

PMID- 1379292
TI  - Interferon-dependent signaling pathways: DNA elements, transcription factors,
      mutations, and effects of viral proteins.

PMID- 1379293
TI  - Differential inactivation of interferons by a protease from human granulocytes.
AB  - Human leukocyte suspensions produced interferon-alpha (IFN-alpha) without
      induction during incubation at 37 degrees C. The highest titers were obtained at
      about 30 million cells/ml. The best yields, approximately 2 IU per 10(6) cells,
      were achieved in medium with or without albumin; serum inhibited the production.
      The uninduced IFN-alpha peaked at 24 h. The titers dropped on further incubation
      due to release of a protease from polymorphonuclear cells. The protease
      inactivated all tested human class I IFNs, but recombinant IFN-alpha 1 was
      clearly more resistant to the enzyme than rIFN-alpha 2. Human IFNs-gamma from
      different sources exhibited striking differences in their sensitivity to the
      protease. Glycosylated natural IFN-gamma from human leukocytes and glycosylated
      rIFN-gamma from CHO cells were relatively resistant, whereas unglycosylated rIFN
      gamma from Escherichia coli was rapidly degraded by the protease. The protease
      was inhibited by PMSF and by greater than or equal to 1% human or fetal bovine
      serum but not by EDTA or less than or equal to 1% human albumin. Its optimum pH
      was between 7 and 8. It was resistant to treatment for 30 min at 56 degrees C.

PMID- 1379294
TI  - Primary intraosseous squamous cell carcinoma arising in a mandibular keratocyst.
AB  - Primary intraosseous carcinoma (P1OC) of the jaws is rare. They either arise de
      novo or as a consequence of malignant transformation of a benign cyst or tumor. A
      56-year-old patient with a P1OC of the mandible arising from an odontogenic
      keratocyst is described.

PMID- 1379295
TI  - Two populations of splenic dendritic cells detected with M342, a new monoclonal
      to an intracellular antigen of interdigitating dendritic cells and some B
      lymphocytes.
AB  - A monoclonal has been isolated that labels an intracellular antigen in dendritic
      cells and some B cells. The M342 hamster immunoglobulin was selected because it
      stained cells in the periarterial sheaths of spleen, the deep cortex of lymph
      node, and the thymic medulla--the same regions in which one finds interdigitating
      cells, the presumptive in situ counterparts of isolated lymphoid dendritic cells.
      M342 labeled an antigen within granules of isolated dendritic cells, but only in
      cells that had been cultured for a day and not in fresh isolates. This extends
      recent findings that most freshly isolated spleen dendritic cells are located in
      the periphery of the white pulp nodule and may serve as precursors for the
      periarterial pool of interdigitating cells, the site for M342 staining in situ.
      By electron microscopic immunolabeling, the M342 antigen was found exclusively in
      a type of multivesicular body. M342 staining was not found in mononuclear
      phagocytes from blood and peritoneal cavity. Peritoneal B cells expressed M342+
      granules, and upon appropriate stimulation splenic B cells developed reactive
      granules as well. We conclude that M342 is a strong marker for interdigitating
      cells. Its existence reveals intracellular specializations in the vacuolar system
      of antigen-presenting cells including subsets of dendritic cells.

PMID- 1379296
TI  - Specific ligation of surface alpha-D-galactosyl epitopes markedly affects the
      quantity of four major proteins secreted by macrophages.
AB  - Activated macrophages (M phi s) have terminal alpha-D-galactosyl (alpha D-Gal)
      residues on their membranes that are not apparent on resting cells. Ligation of
      these epitopes with Griffonia simplicifolia I-B4 (GSI-B4), a lectin that has
      specificity for alpha-D-Gal residues, alters selected M phi functions. To explore
      the mechanism(s) that may be responsible for some of the functional changes,
      alterations in the secretory pattern of [35S]methionine-labeled proteins were
      assessed when cells were cultured with or without this ligand. The proteins were
      identified by Western blots and quantitated. Interestingly, alpha-D-Gal ligation
      proved to decrease the secretion of some proteins while increasing the secretion
      of others. Some of the most significant changes were observed in four proteins:
      fibronectin and transglutaminase were down-regulated by 55 and 66% respectively,
      while plasminogen activator inhibitor type 2 was increased by 259% and
      collagenase was increased 1000-fold. These observations show that the emergence
      of new oligosaccharide epitopes, such as alpha-D-Gal, concomitant with M phi
      activation may serve to mediate the transduction of signals that cause
      quantitative changes in the elaboration of diverse M phi products. The biologic
      significance of the four identified proteins has been well established.
      Fluctuations in their levels are likely to play a role at sites of chronic
      inflammation.

PMID- 1379297
TI  - PMN binding to P-selectin is inhibited by sulfatide.
AB  - The endothelial adhesion protein P-selectin binds to a ligand present on the
      surface of leukocytes. We have characterized the binding interaction between P
      selectin and polymorphonuclear leukocytes (PMNs) in an in vitro assay. These
      studies have utilized a soluble chimeric protein termed receptor globulin (Rg),
      which consists of the lectin-EGF-CR-CR extracellular domains of P-selectin fused
      to a human immunoglobulin G Fc domain. The PMNs bound to immobilized Rg in a
      saturable and concentration-dependent manner. The binding was specific for the
      Rg, as preincubation of the cells with soluble Rg inhibited binding to
      immobilized Rg, and binding was dependent on the presence of free divalent
      cations. The PMNs expressed a ligand for both P-selectin and E-selectin but not
      for L-selectin. Previously it was shown that sulfatide is a ligand for P-selectin
      binding in transformed cells. We have demonstrated that the presence of sulfatide
      in the P-selectin-PMN adhesion assay inhibits binding in a dose-dependent manner.

PMID- 1379298
TI  - Direct interaction between an antigen-specific B cell clone and an MHC class II
      reactive helper T cell clone.
AB  - TP67.14 established by somatic hybridization is a 2,4,6-trinitrobenzenesulfonic
      acid (trinitrophenyl, TNP)-specific B cell clone with a receptor molecule for TNP
      on the cell membrane, and MS202 is an interleukin-2 (IL-2)-dependent T helper
      (Th) cell clone reactive to auto-MHC class II antigens (IAk and IEk) as
      previously reported. In the present study it was shown that MS202 considerably
      induced the maturation of TP67.14 into anti-TNP plaque-forming cells (PFCs), and
      this response was markedly augmented by the addition of TNP-keyhole limpet
      hemocyanin (KLH). Recombinant cytokines and the culture supernatant of MS202 with
      TP67.14 did not affect the generation of anti-TNP antibodies by TP67.14. Also,
      neither anti-IL-4 nor anti-IL-5 monoclonal antibody (mAb) inhibited the
      maturation of TP67.14 mediated by MS202. The differentiative effect of MS202 on
      TP67.14 was completely lost when each cell was separately cultured using a
      semipermeable membrane. Monoclonal antibodies against LFA-1 beta molecules
      significantly blocked the development of anti-TNP PFCs induced by MS202, as well
      as anti-IAk and anti-IEk mAbs. Interestingly, the plasma membrane-enriched
      fraction (PM) derived from MS202 exhibited much more differentiative effects on
      TP67.14 treated with TNP-KLH than PM from other T cell lines and concanavalin A
      induced T lymphoblasts. In addition, TNP-conjugated PM from MS202 by itself
      induced a great number of anti-TNP PFCs. The present findings indicate that MS202
      is capable of inducing the maturation of TP67.14, which is considered to
      represent a population of B cells with antigen specificity in a late lineage of B
      cell maturation, through direct cell contact but not soluble factors. This
      suggests that B cells with antigen specificity, in the presence of antigen, can
      be induced to mature into antibody-secreting cells through direct contact with Th
      cells; in this process surface major histocompatibility complex class II and
      lymphocyte function-associated antigen 1 (LFA-1) molecules are directly involved
      and the cell membrane derived from Th cells provides a transductional signal for
      maturation of B cells with antigen specificity in the presence of antigen.

PMID- 1379299
TI  - Malpractice, steroids and avascular necrosis of bone.

PMID- 1379300
TI  - Learning and behavioral--emotional problems of children born preterm at second
      grade.
AB  - A longitudinal prospective study examined the question, "which child and family
      factors discriminate between children born preterm who are characterized by the
      presence or absence of learning or behavioral-emotional problems at second
      grade?" Assessments were completed during the child's hospital stay at birth, at
      4, 8, and 24 months, and 8 years of age for 68 children born preterm and their
      mothers. Discriminant analyses identified the variables that statistically
      maximized the differentiation between two groups of children defined to exhibit
      or not exhibit school age problems. Three categories of discriminators were used
      in the analyses: infant status, family interactive quality, and family context.
      The three significant discriminators were variables from the family categories.
      The results of this study highlight the importance of understanding the presence
      or absence of school age problems from a multivariate model of development that
      takes into account the quality of the child's interactions within the family
      during early childhood and school age and the current stress levels in the family
      context.

PMID- 1379301
TI  - Colonization characteristics of enteric neural crest cells: embryological aspects
      of Hirschsprung's disease.
AB  - This study explores the development of the enteric nervous system in avian
      embryos. Particular emphasis was given to colonization characteristics of neural
      crest cells present in primitive enteric ganglia. By coculturing neuronal and
      aneuronal gut of quail and chicken embryos, we investigated if and when neural
      crest cells in primitive enteric ganglia could detach from these ganglia,
      migrate, and colonize adjacent chicken gut. Quail neural crest cells were
      identified using the quail nucleolar marker and the HNK-1 antibody. Enteric
      neurons were identified using three monoclonal antibodies directed against
      neurofilament proteins. We found that neural crest cells detached from primitive
      ganglia in neuronal quail gut from E6 till E9, whereas neural crest cells did not
      leave enteric ganglia from E10 gut. These observations show that there is a
      transient phase during which enteric neural crest cells can leave the gut. To
      determine whether neural crest cells could colonize neuronal gut we cocultured
      neuronal gut or the neural primordium and neuronal chicken gut (E11). We found
      that quail neural crest cells do not colonize neuronal E11 gut, whereas they do
      colonize aneuronal gut of the same age. We suggest that aneuronal gut attracts
      neural crest cells by diffusing factors.

PMID- 1379302
TI  - Distribution of ICAM-1, LFA-3 and HLA-DR in healthy and diseased gingival
      tissues.
AB  - Cell adhesion molecules are involved in recognition and effector aspects of the
      host response, including the control of migration of leukocytes into inflammatory
      sites. In this study we have demonstrated that the distribution of three cell
      surface molecules involved in cell interactions, ICAM-1, LFA-3 and HLA-DR is
      distinct and different in healthy and diseased gingival tissue. ICAM-1 was
      consistently expressed by junctional epithelial cells in healthy gingiva and by
      pocket epithelium in diseased gingiva but was not detectable on the majority of
      keratinocytes in external gingival epithelium. ICAM-1 was also expressed by
      endothelial cells of gingival blood vessels and a subset of leukocytes in the
      infiltrated connective tissue in both healthy and diseased gingiva. HLA-DR and
      LFA-3 were also expressed by epithelial cells and endothelial cells but in
      patterns which were distinctly different from ICAM-1.

PMID- 1379303
TI  - Unknown syndrome in sibs: pili torti, growth delay, developmental delay, and mild
      neurological abnormalities.
AB  - We present male and female sibs of consanguineous parents with features including
      pili torti with unusual hair shaft electron microscopic (EM) findings, growth
      delay, developmental delay, and mild to moderate neurological abnormalities. The
      features of the cases presented here have not been noted in the previously
      reported clinical syndromes in which pili torti may be found.

PMID- 1379304
TI  - Important 2'-hydroxyl groups in model substrates for M1 RNA, the catalytic RNA
      subunit of RNase P from Escherichia coli.
AB  - The role of 2'-hydroxyl groups in a model substrate for RNase P from Escherichia
      coli was studied using mixed DNA/RNA derivatives of such a substrate. The
      presence of the 2'-hydroxyl groups of nucleotides at positions -1 and -2 in the
      leader sequence and at position 1, as well as at the first C in the 3'-terminal
      CCA sequence, are important but not absolutely essential for efficient cleavage
      of the substrate by RNase P or its catalytic RNA subunit, M1 RNA. The 2'-hydroxyl
      groups in the substrate that are important for efficient cleavage also
      participate in the binding of Mg2+. An all-DNA external guide sequence (EGS) can
      efficiently render a potential substrate, derived from the model substrate,
      susceptible to cleavage by the enzyme or its catalytic RNA subunit. Furthermore,
      both DNA and RNA EGSs turn over during the reaction with RNase P in vitro. The
      identity of the nucleotide at position 1 in the substrate, the adjacent Mg(2+)
      binding site in the leader sequence, and the junction of the single and double
      stranded regions are the important elements in the recognition of model
      substrates, as well as in the identification of the sites of cleavage in those
      model substrates.

PMID- 1379305
TI  - Ribosomal RNA identity elements for ricin A-chain recognition and catalysis.
      Analysis with tetraloop mutants.
AB  - Ricin is a cytotoxic protein that inactivates ribosomes by hydrolyzing the N
      glycosidic bond between the base and the ribose of the adenosine at position 4324
      in eukaryotic 28 S rRNA. Ricin A-chain will also catalyze depurination in naked
      prokaryotic 16 S rRNA; the adenosine is at position 1014 in a GAGA tetraloop. The
      rRNA identity elements for recognition by ricin A-chain and for the catalysis of
      cleavage were examined using synthetic GAGA tetraloop oligoribonucleotides. The
      RNA designated wild-type, an oligoribonucleotide (19-mer) that approximates the
      structure of the ricin-sensitive site in 16 S rRNA, and a number of mutants were
      transcribed in vitro from synthetic DNA templates with phage T7 RNA polymerase.
      With the wild-type tetraloop oligoribonucleotide the ricin A-chain-catalyzed
      reaction has a Km of 5.7 microM and a Kcat of 0.01 min-1. The toxin alpha-sarcin,
      which cleaves the phosphodiester bond on the 3' side of G4325 in 28 S rRNA, does
      not recognize the tetraloop RNA, although alpha-sarcin does affect a larger
      synthetic oligoribonucleotide that has a 17-nucleotide loop with a GAGA sequence;
      thus, there is a clear divergence in the identity elements for the two toxins.
      Mutants were constructed with all of the possible transitions and transversions
      of each nucleotide in the GAGA tetraloop; none was recognized by ricin A-chain.
      Thus, there is an absolute requirement for the integrity of the GAGA sequence in
      the tetraloop. The helical stem of the tetraloop oligoribonucleotide can be
      reduced to three base-pairs, indeed, to two base-pairs if the temperature is
      decreased, without affecting recognition; the nature of these base-pairs does not
      influence recognition or catalysis by ricin A-chain. If the tetraloop is opened
      so as to form a GAGA-containing hexaloop, recognition by ricin A-chain is lost.
      This suggests that during the elongation cycle, a GAGA tetraloop either exists or
      is formed in the putative 17-member single-stranded region of the ricin domain in
      28 S rRNA and this bears on the mechanism of protein synthesis.

PMID- 1379306
TI  - Effects of acidic fibroblast growth factor on hippocampal long-term potentiation
      in fasted rats.
AB  - Effects of human recombinant acidic fibroblast growth factor (haFGF) on long-term
      potentiation (LTP) and the increase of the spike amplitude induced by weak
      tetanic stimulation were investigated and compared with those of CS23 (modified
      human basic FGF) in the dentate gyrus of fasted and nonfasted rats. haFGF didn't
      influence the LTP induced by the tetanus of 100 pulses at 100 Hz in both 24 hr
      fasted and non-fasted rats. On the other hand, the tetanus of 20 pulses at 60 Hz
      significantly enhanced the amplitude of population spike and facilitated the
      generation of LTP by the i.c.v. injection of 10 microliters of 20-40
      micrograms/ml haFGF in 24 hr fasted rats but not in non-fasted rats. However, 40
      micrograms/ml CS23 induced LTP when the tetanus of 20 pulses at 60 Hz was applied
      in both fasted and non-fasted states. These results suggest that haFGF might be
      one of the regulating factors of feeding and memory.

PMID- 1379307
TI  - Acrylamide exposure preferentially impairs axonal transport of glycoproteins in
      myelinated axons.
AB  - The right L5 dorsal root ganglion of adult rats exposed to acrylamide (40 mg/kg
      body weight/day for nine consecutive days) was injected with either
      [3H]methionine or [3H]glucosamine. After allowing incorporation into
      macromolecules and axonal transport to proceed for 5 hr, the distribution of
      radioactivity in cross sections and longitudinal sections of sciatic nerve was
      determined by autoradiography. Control and treated animals showed no difference
      in distribution of label within the sciatic nerve with respect to rapidly
      transported proteins labelled with [3H]methionine. In control animals the
      distribution of rapidly transported glycoproteins labelled with [3H]glucosamine
      was similar to that found for [3H]methionine-labelled proteins. In contrast,
      acrylamide-exposed rats had a very different distribution of labelled
      glycoproteins; there was a marked paucity of label in the myelinated axons. We
      interpret this result as indicating that acrylamide preferentially inhibits
      glycosylation or axonal transport of glycoproteins in neurons bearing myelinated
      axons.

PMID- 1379308
TI  - Cyclic AMP-induced upregulation of proteolipid protein and myelin associated
      glycoprotein gene expression in C6 cells.
AB  - A model culture system of C6 rat glioma cells was used to test the involvement of
      cAMP in the regulation of the myelin PLP and MAG genes. The treatment of cells
      with isoproterenol (10(-5) to 10(-8) M) upregulated the expression of the PLP and
      MAG genes in a concentration-dependent manner. The mRNA for PLP reached a maximum
      (sevenfold higher than in control cells) after about 12-24 hr, then declined to
      approximately fourfold over the control level. The response of MAG gene was
      delayed by at least 36 hr, and the level of MAG mRNA reached a maximum of
      approximately 48-fold over the control level on the fourth day in culture. The co
      administration of propranolol blocked the effect of isoproterenol, whereas 10(-5)
      M forskolin simulated the effect of isoproterenol, indicating a role of cAMP in
      the signal transduction cascades leading to upregulation of the myelin genes.
      However, the dissimilarity in the timing and the extent of upregulation of the
      PLP and MAG genes by cAMP-stimulating agents indicate the existence of different
      intracellular mechanisms for the activation of these two genes. Cycloheximide
      blocked the stimulatory effect of isoproterenol on both the PLP and MAG genes,
      indicating that the effect of cAMP on the myelin genes is mediated by protein
      product(s) of other cAMP-response gene(s).

PMID- 1379309
TI  - Endotoxin of Pseudomonas pseudomallei detected by the body weight-decreasing
      reaction in mice and comparison of it with those of P. cepacia and P. aeruginosa.
AB  - The heat-treated whole cells, culture supernatants, and extracted endotoxin
      preparations of Pseudomonas pseudomallei were examined for endotoxin by the mouse
      body weight-decreasing (BWD) test. The experiments were conducted also with those
      of P. cepacia and P aeruginosa. Endotoxin was detected in all the samples of P.
      pseudomallei. Endotoxin of P. cepacia was detected in whole cells, but not in
      culture supernatant. The BWD activity of P. aeruginosa was 30 times as high as
      that of P. pseudomallei. This result was confirmed by the experiments with
      endotoxin preparations. In the limulus amebocyte lysate gelation (LAL) test,
      however, the endotoxin preparations of the two species showed the same level of
      activity.

PMID- 1379310
TI  - [Fundamental evaluation of ELSA.F-beta HCG kit as an immunoradiometric assay
      specific for serum beta HCG].
AB  - We evaluated ELSA.F-beta HCG kit as an immunoradiometric assay (IRMA) specific
      for serum beta human chorionic gonadotropin (beta hCG). This IRMA was found to be
      highly sensitive to serum beta hCG; the minimum detectable concentration of beta
      hCG was 0.05 ng/ml. No significant effects on the standard curves were observed
      when first and second incubation time and temperature were varied from 30 min to
      240 min and from 4 degrees C to 37 degrees C, respectively. Commercial LH, FSH,
      and TSH had little effect on the assay system; the cross-reactivity of commercial
      hCG was 2.5%, and 0.14% after unconjugated beta hCG with alpha-subunit was
      absorbed with ELSA-tube. Multiple dilutions of sera of pregnancy resulted in
      curves paralleling that obtained using standard beta hCG; the recovery of beta
      hCG added to the serum was 98.1 +/- 2.5% (mean +/- SD), and mean coefficient of
      variation of the interassay reproducibility of serum beta hCG (n = 10) was 6.7 +/
      2.8 (SD)%. Serum beta hCG concentration measured using ELSA.F-beta HCG kit was
      well correlated with that measured using conventional beta hCG RIA kit (r =
      +0.961, p less than 0.01), although values were lower than those measured with
      the latter (y = 0.35x + 0.26). Our results suggest that ELSA.F-beta HCG kit is a
      useful assay system for serum beta hCG.

PMID- 1379311
TI  - A simulation of the genetic periodicities modulo 2 and 3 with processes of
      nucleotide insertions and deletions.
AB  - Recently, a new genetic process termed RNA editing has been identified showing
      insertions and deletions of nucleotides in particular RNA molecules. On the other
      hand, there are a few non-random statistical properties in genes: in particular,
      the periodicity modulo 3 (P3) associated with an open reading frame, the
      periodicity modulo 2 (P2) associated with alternating purine/pyrimidine
      stretches, the YRY(N)6YRY preferential occurrence (R = purine = adenine or
      guanine, Y = pyrimidine = cytosine or thymine, N = R or Y) representing a "code"
      of the DNA helix pitch, etc. The problem investigated here is whether a process
      of the type RNA editing can lead to the non-random statistical properties
      commonly observed in genes. This paper will show in particular that: The process
      of insertions and deletions of mononucleotides in the initial sequence [YRY(N)3]*
      [series of YRY(N)3] can lead to the periodicity modulo 2 (P2). The process of
      insertions and deletions of trinucleotides in the initial sequence [YRY(N)6]*
      [series of YRY(N)6] can lead to the periodicity modulo 3 (P3) and the YRY(N)6YRY
      preferential occurrence. Furthermore, these two processes lead to a strong
      correlation with the reality, namely the mononucleotide insertion/deletion
      process, with the 5' eukaryotic regions and the trinucleotide insertion/deletion
      process, with the eukaryotic protein coding genes.

PMID- 1379312
TI  - Phase II study of mitoxantrone and 5-azacytidine for accelerated and blast crisis
      of chronic myelogenous leukemia: a study of the Eastern Cooperative Oncology
      Group.
AB  - A total of 40 evaluable patients were treated for blastic crisis of chronic
      myelogenous leukemia with mitoxantrone, 12 mg/m2 per day for three days and 5
      azacytidine 150 mg/m2 per day for 5 days. Toxicity was primarily hematologic and
      was manageable. The overall response rate was 23%, including five complete
      responders, two partial responders, and two with hematologic improvement.
      Cytogenetic and immunophenotypic characterization of the leukemia was performed
      on all patients with aspirable bone marrow, and these results were correlated
      with response and survival, but did not have predictive value once the patient
      was in blastic crisis. Only initial platelet count (p = 0.02), hemoglobin (p =
      0.03), and lower white blood cell count (p = 0.09) were somewhat predictive of
      response. Lack of hepatic involvement (p = 0.05), lower white blood cell count
      (0.05), and higher platelet count (p = 0.02) were predictive of prolonged
      survival. Although response did not strongly correlate with survival, one third
      of responders were alive at one year. This regimen produces results similar to
      those of other recently published regimens in this disease. Earlier intervention
      and more effective therapy is necessary in these patients.

PMID- 1379313
TI  - BCR/ABL confers growth factor independence upon a murine myeloid cell line.
AB  - The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated
      tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes,
      BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines.
      To investigate the ability of BCR/ABL to generate growth factor independence in
      myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was
      transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54
      and A74 were capable of IL-3 independent growth and tumor formation in syngeneic
      mice. Relief of growth factor dependence was not mediated by autocrine release of
      IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was
      greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant
      constitutive expression of c-myc, c-jun, and c-fos was observed in the
      p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc
      expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor
      c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL
      transformation and relief of IL-3 dependence involve not only pathways that can
      substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also
      pathways that recruit constitutive c-jun and c-fos expression.

PMID- 1379314
TI  - Isolation and characterization of human hematopoietic progenitor cells: an
      effective method for positive selection of CD34+ cells.
AB  - Immunomagnetic beads are well suited for positive selection of CD34+ cells.
      However, both unspecific binding of beads to cells as well as the effectiveness
      of detachment of beads from cells may represent significant problems. We used an
      anti-Fab antiserum (DETACHaBEAD, Dynal) for rapid and effective detachment of
      immunomagnetic beads from the positively selected cells. By this detachment
      technique, the cells remained phenotypically unaltered. To reduce unspecific
      binding, we have coated various anti-CD34 monoclonal antibodies directly to
      paramagnetic beads M450 (Dynal). Use of beads coated with BI-3C5 was found to be
      optimal with regard to yield and purity of the isolated cells. The yield was on
      average 1.5% (range 0.5-2.5%) of bone marrow mononuclear cells and the purity was
      usually greater than 95% CD34+ cells of the isolated cells. Subpopulations of the
      cells expressed myeloid markers (CD13, CD33, and to a lesser extent CD15 and
      CD14) or early B-lineage markers (CD19 and CD10). Most of the cells expressed
      CD38, and a majority of the cells also expressed CD41. In general, most of the
      CD34+ cells with low forward scatter expressed B-lineage markers, as was also the
      case for the few contaminating CD34- cells which were found to be predominantly
      CD37+ mature B cells. Reactivity with antibodies against T-lineage markers (CD2,
      CD3, CD4, CD7, and CD8) was generally detected only on 1-2% of the cells or less.
      Isolated cells responded to interleukin 3, granulocyte-macrophage colony
      stimulating factor, mast cell growth factor, and/or granulocyte colony
      stimulating factor alone or in combinations in short-term liquid cultures. The
      cells were also markedly enriched for granulocyte-macrophage colony-forming units
      as well as for early progenitor cells capable of forming blast colonies on
      preformed stromal feeder layers. Moreover, the CD34- population was depleted of
      70-80% of CFU-GM and cells capable of blast colony formation. Thus, we conclude
      that the isolated cells are phenotypically unaltered after isolation, and show a
      normal response in various in vitro assays.

PMID- 1379315
TI  - Effects of short-term liquid cultures of peripheral blood mononuclear cells with
      recombinant human granulocyte or granulocyte-macrophage colony-stimulating factor
      in cytogenetic studies of myelofibrosis with myeloid metaplasia.

PMID- 1379316
TI  - Release of sensory CGRP by hypertonic NaCl is not blocked by tetrodotoxin, omega
      conotoxin, nifedipine and ruthenium red.
AB  - Hypertonic NaCl (160 mM added to the physiological salt solution) releases CGRP
      in a Ca(2+)-dependent manner from capsaicin-sensitive sensory nerves of the rat
      urinary bladder. The NaCl (160 mM)-evoked CGRP release was not affected by
      tetrodotoxin (0.3 microM), nifedipine (1 microM), omega-conotoxin (0.1 microM)
      and ruthenium red (10 microM). NaCl (160 mM)-evokes release of sensory
      neuropeptides without the involvement of axon reflexes, and by promoting Ca2+
      influx via a dihydropyridine omega-conotoxin and ruthenium red insensitive
      pathway.

PMID- 1379317
TI  - Interferon therapy for multiple sclerosis.
AB  - Laboratory findings that suppressor cell function is improved with beta
      interferon therapy and that gamma interferon activity is inhibited by beta
      interferon provide support for the hypothesis that beta interferon will have a
      significant therapeutic effect on relapse rates in multiple sclerosis.

PMID- 1379318
TI  - A metal-binding motif implicated in RNA recognition by an aminoacyl-tRNA
      synthetase and by a retroviral gene product.
AB  - A randomly generated mutation in Escherichia coli alanine tRNA synthetase
      compensates for a mutation in its cognate tRNA. The enzyme's mutation occurs next
      to a Cys-X2-Cys-X6-His-X2-His metal-binding motif that is distinct from the zinc
      finger motif found in some DNA-binding proteins. Instead, the synthetase's metal
      binding domain resembles the Cys-X2-Cys-X4-His-X4-Cys metal-binding domain of the
      gag gene product of retroviruses. For Ala-tRNA synthetase, the metal bound at the
      Cys-His motif is important specifically for the tRNA-dependent step of catalysis,
      and the enzyme-tRNA interaction is dependent on the geometry of metal co
      ordination to the enzyme. These data, and the demonstrated sensitivity of RNA
      packaging to mutations in the metal-binding domain of the gag gene product of
      retroviruses, suggest that an aminoacyl-tRNA synthetase and retroviruses have
      adopted a related metal-binding motif for RNA recognition.

PMID- 1379320
TI  - Molecular analysis of the rfb gene cluster of Salmonella serovar muenchen (strain
      M67): the genetic basis of the polymorphism between groups C2 and B.
AB  - The rfb (O antigen) gene cluster of group C2 Salmonella differs from that of
      group B in a central region of 12.4 kb: we report the sequencing of this region
      of strain M67 (group C2) and a subsequent comparison with the central region of
      strain LT2 (group B). We find a block of seven open reading frames unique to
      group C2 which encode the O antigen polymerase (rfc) and the transferases
      responsible for assembly of the group C2 O antigen. The remaining rfb genes are
      common to strains M67 and LT2, but rfbJ (CDP-abequose synthase) and rfbM and rfbK
      (GDP-mannose synthesis), which are immediately adjacent to the central region,
      are highly divergent. All these genes have a low G+C content and appear to have
      been recent additions to Salmonella enterica. We discuss the evolutionary
      significance of the arrangement and divergence of the genes in the polymorphism
      of the rfb cluster.

PMID- 1379319
TI  - Mip protein of Legionella pneumophila exhibits peptidyl-prolyl-cis/trans
      isomerase (PPlase) activity.
AB  - Legionella pneumophila is an intracellular parasite which is able to survive and
      multiply in human monocytes and alveolar macrophages. The Mip (macrophage
      infectivity potentiator) protein has been shown to be an essential virulence
      factor. A search of translated nucleic acid data bases has shown that the Mip
      protein from strain Wadsworth possesses regions homologous to those found in the
      FK506-binding proteins (FKBPs) of several different eukaryotic organisms. FKBPs
      are able to bind to the immunosuppressant macrolide FK506 and possess peptidyl
      prolyl cis/trans isomerase (PPIase) activity. The gene coding for the Mip protein
      was cloned from the chromosome of L. pneumophila strain Philadelphia I and
      sequenced. It was synthesized in Escherichia coli K-12 and after purification it
      exhibited PPIase activity catalysing the slow cis/trans isomerization of prolyl
      peptide bonds in oligopeptides. Mip is inhibited by FK506 and fully resistant to
      cyclosporin A, as was also found for the recently characterized FKBP-type PPIases
      of eukaryotes. However, the N-terminal extension of Mip and/or the substitutions
      of the variable amino acids in the C-terminal FKBP core leads to variations, when
      compared with eukaryotic FKBPs, in substrate specificity with the oligopeptide
      substrates of type Suc-Ala-Xaa-Pro-Phe-4-nitroanilide. Nevertheless, the
      Legionella Mip factor represents a bacterial gene product which shares some
      characteristics normally found in eukaryotic proteins. In view of the activity of
      PPIases in protein-folding reactions, such prokaryotic FKBP analogues may
      represent a new class of bacterial pathogenicity factors.

PMID- 1379321
TI  - Differential role of endothelial function on vasodilator responses in series
      arranged arterioles.
AB  - Both in vitro and in vivo studies have revealed that removal of vascular
      endothelial cells abolishes the vasodilation to acetylcholine (Ach) but not
      sodium nitroprusside (SNP). Differential properties of endothelial cells in the
      series-arranged arterioles to vasodilator responses have not been studied. In
      this study, the cheek pouch microcirculation from the golden syrian hamster
      anesthetized with sodium pentobarbital (6 mg/100 g body wt, ip) was prepared for
      intravital microscopy. Measurements of lumen diameters of small series-arranged
      arterioles (2nd- and 4th-order) were made before, during, and after topical
      microapplication of different doses of either Ach or SNP. After control
      measurements, a light-dye (L-D) technique utilizing sodium fluorescein (FITC
      dextran(150K), 50 mg/100 g body wt, iv) and illuminating a discrete area of the
      arteriole with 490-nm-wavelength light for 3 (4th) or 10 (2nd) min was used to
      impair endothelial cell function without damaging vascular smooth muscle cells.
      Responses to vasoactive substances for both 4th-order (10-20 microns) and second
      order (30-50 microns) arterioles were retested. Vasodilatory responses to 10(-7)
      M Ach and SNP also were tested with and without the presence of NG-monomethyl L
      arginine (L-NMMA), an inhibitor of EDRF/NO formation. In the control state, Ach
      and SNP produced a focal, dose-dependent increase in diameter in all arterioles
      tested. Endothelial impairment by L-D treatment significantly suppressed the
      vasodilator response to Ach in 4th- but not 2nd-order arterioles, whereas the SNP
      response was not significantly affected. Consistent with these observations, L
      NMMA treatment significantly attenuated Ach-induced vasodilation in 4th-order
      arterioles, but it had no effect on 2nd-order arterioles. These studies document
      further the role of the endothelium in local modulation of arteriolar diameter in
      response to acetylcholine and demonstrate a differential effect for this response
      in series-arranged microvessels. Thus, there may be a heterogeneous distribution
      of endothelial cell functions for modulating vasodilator activity in
      microvessels.

PMID- 1379322
TI  - Induction of chromosomal aberrations by camptothecin in root-tip cells of Vicia
      faba.
AB  - When root-tip cells of Vicia faba were exposed during early and middle interphase
      to camptothecin (Cpt), the aberrations obtained were exclusively of the chromatid
      type and tended to be localized in late replicating heterochromatic regions of
      the chromosomes. In these respects the clastogenic effect of Cpt resembles that
      of agents that act by an S-phase-dependent mechanism. In contrast to typical S
      phase-dependent agents, Cpt produced lesions capable of giving rise to
      aberrations only in S-phase cells that were synthesizing DNA at the time of
      treatment. The dependence on ongoing DNA synthesis was suggested in
      autoradiographic experiments and by the fact that the clastogenic effect of Cpt
      was strongly suppressed by hydroxyurea, an inhibitor of DNA synthesis. After Cpt
      treatments, there were many more cells with 3-12 aberrations and far fewer cells
      with 0, 1 or 2 aberrations than expected on the basis of a Poisson distribution.
      Cpt further differed from typical S-phase-dependent agents by being capable of
      inducing lesions in the G2 phase that give rise to chromosomal aberrations in the
      first mitosis after treatment. This effect was obtained at Cpt concentrations
      around 10 microM, whereas only 0.03 microM Cpt was required to produce chromatid
      aberrations in the S phase. Results of G2-phase experiments with Cpt and 5
      fluorodeoxyuridine, an inhibitor of DNA synthesis, suggest that DNA synthesis is
      required for the clastogenic effect of Cpt not only during the S phase, but also
      during the G2 phase, although the DNA syntheses involved are both quantitatively
      and qualitatively different.

PMID- 1379323
TI  - Effect of low temperature on radiation-induced genetic damage in Drosophila
      melanogaster: response of motile sperm and late spermatids.
AB  - The response of fully mature motile sperm and late spermatids when challenged
      with X-radiation at 0 degrees C has been studied in sex-linked recessive lethals,
      II-III translocations and dominant lethality experiments. At 0 degrees C a
      significant increase in both mutagenic and clastogenic damage was detected
      compared to that obtained at 24 degrees C. Furthermore, the results of
      experiments performed with different postirradiation temperatures demonstrate
      that the low temperature during irradiation was the sole factor responsible for
      the observed increase. In the recessive lethal and translocation tests the
      response of late spermatids was higher than that shown by motile spermatozoa. As
      a whole, the results, which are rather similar to data reported on the effect of
      irradiation in oxygen of the same cell stages, suggest that the low temperature
      acted as a dose-modifying factor.

PMID- 1379324
TI  - Formation of new heterocyclic amine mutagens by heating creatinine, alanine,
      threonine and glucose.
AB  - A mixture of alanine, threonine, creatinine and glucose was heated in diethylene
      glycol and water (5:1, v/v) for 15 min at 200 degrees C. The mutagens formed were
      purified by high-performance liquid chromatography using the Ames/Salmonella
      mutagenic activity to guide the purification. The structures of the purified
      mutagens were determined using UV absorption, mass and NMR spectrometry. A new
      mutagenic compound with a mass number of 217 was found and its mass spectrum did
      not correspond to any known mutagen derived from food. This new compound
      accounted for 4% of the total mutagenic activity. Other mutagenic compounds were
      identified as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline), 4,8-DiMeIQx
      (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), and a new mutagen 4,7,8
      TriMeIQx (2-amino-3,4,7,8-tetramethylimidazo[4,5-f]quinoxaline) with a mutagenic
      activity of 73,000 TA98 revertants per microgram. The percentage of the mutagenic
      activity attributable to MeIQx, 4,8-DiMeIQx and 4,7,8-TriMeIQx was 10%, 70% and
      3%, respectively. The yield of MeIQx, 4,8-DiMeIQx and 4,7,8-TriMeIQx was 10, 36
      and 6 nmole/mmole creatinine. The formation of TriMeIQx from natural meat
      components suggests that this new quinoxaline mutagen may be present in cooked
      foods.

PMID- 1379325
TI  - In vitro and in vivo mutagenicity studies on sporidesmin, the toxin associated
      with facial eczema in ruminants.
AB  - Sporidesmin, a fungal toxin with widespread distribution within New Zealand, is
      thought to exert toxic effects through oxidative damage. The purified chemical
      was tested for its ability to cause point mutations in four strains of Salmonella
      typhimurium (TA98, TA100, TA102 and TA1537), in the presence and absence of
      exogenous metabolic activation. Although toxic effects were seen at
      concentrations exceeding 400 mu gl/plate, there were no significant increases in
      revertant colonies. In strain TA102, these results were not modified by the
      presence of glutathione. In AA8 Chinese hamster cells, sporidesmin acted as a
      potent clastogen, causing chromosomal breaks at concentrations as low as 3 ng/ml,
      where there was very little reduction in cell viability. Effects were primarily
      at the chromatid level, but some chromosomal events were also seen. Following low
      doses, the most common events were chromatid deletions and induction of double
      minute chromosomes. Interchange events occurred at concentrations of 10 ng/ml and
      above. The most common of these events was an incomplete chromatid interchange,
      although some examples of complete chromatid and chromosomal interchange were
      seen. These in vitro experiments were subsequently extended to an in vivo study
      of sporidesmin-induced lymphocytic micronuclei (MN) in sheep. In a double blind
      experiment, 5 sheep were treated with a single high dose of sporidesmin. Blood
      samples were taken from these, and from 5 untreated sheep, at various intervals
      before and after treatment. Peripheral blood lymphocytes cultures were harvested
      and scored for MN in cytokinesis-blocked cells, as a measure of clastogenic
      activity of sporidesmin in vivo. Following decoding, statistical analysis of the
      data revealed no significant differences between the MN levels in peripheral
      blood lymphocytes of sporidesmin-treated and untreated sheep. Although the
      possibility still exists that clastogenic effects could occur in other species,
      the data indicate that sporidesmin is not a clastogen in sheep, even though this
      species is highly susceptible to the toxic effects of sporidesmin.

PMID- 1379326
TI  - Comparative investigation of cyclophosphamide action on bone marrow cells of the
      Armenian hamster and 4 other species of rodents.
AB  - We studied the clastogenic action of cyclophosphamide (CP) on bone marrow cells
      of the Armenian hamster (AH), Cricetulus migratorius. CP induced a dose-dependent
      linear increase in aberrant cells. The maximal cytogenetic action was observed 12
      h after CP treatment. Male and female AHs were similarly sensitive to the
      clastogenic action of CP. We compared CP clastogenicity at a dose of 25 mg/kg on
      bone marrow cells of AHs, mice, rats, guinea pigs and Chinese hamsters 24 h after
      treatment. We observed that this dose of CP induced only 2.8% aberrant cells in
      bone marrow of AHs, but 42.8%, 32.2%, 25% and 14.6% aberrant cells in bone marrow
      of guinea pigs, rats, mice and Chinese hamsters respectively. AHs are much more
      resistant to the metaphase-arresting action of colchicine than other species of
      rodents (e.g., the colchicine dose for AHs is 100-fold more than for rats). Thus
      AHs are the most resistant of all rodent species studied to the clastogenic
      action of CP.

PMID- 1379327
TI  - Modulation by novobiocin of sister-chromatid exchanges induced by tumor necrosis
      factor in human lymphocytes.
AB  - The effect of the antibiotic novobiocin on human recombinant tumor necrosis
      factor (TNF)-induced sister-chromatid exchanges (SCEs) were examined in human
      peripheral blood lymphocytes. TNF, when introduced in a dose range of 10-1000
      U/ml at the initiation of culture, was found to cause a significant increase in
      SCE frequency. The simultaneous addition of TNF and novobiocin (25 micrograms/ml)
      in the assay resulted in no increase of SCE frequency. Delayed (for 24 h)
      addition of novobiocin suppressed the induction of SCEs by 50, 100 and 500 U/ml
      but not by 1000 U/ml of TNF.

PMID- 1379328
TI  - The effect of X-irradiation on cell cycle progression and chromatid aberrations
      in stimulated human lymphocytes using cohort analysis studies.
AB  - Stage sensitivity for the production of chromatid-type aberrations and mitotic
      delay has been investigated in a stimulated human lymphocyte population,
      following an absorbed dose of 1.5 Gy 250 kVp X-rays. BrdU replication banding was
      used to obtain a fine analysis of the cell cycle and to permit cohort analysis.
      Fluctuations in yield with sample time were found for all aberration categories,
      but these could not be related simply to either the developmental stage of the
      cells at time of exposure, or to the time-to-run to metaphase. In general G2 and
      late S cells had higher aberration yields than early S and pre S cell
      populations. Mitotic delay and perturbation at this dose extends to all sub
      phases of S and is as great, if not greater, in the earliest S cells as it is in
      G2.

PMID- 1379329
TI  - Different modifications by vanillin in cytotoxicity and genetic changes induced
      by EMS and H2O2 in cultured Chinese hamster cells.
AB  - The modifying effects of vanillin on the cytotoxicity and 6-thioguanine (6TG)
      resistant mutations induced by two different types of chemical mutagens, ethyl
      methanesulfonate (EMS) and hydrogen peroxide (H2O2), were examined using cultured
      Chinese hamster V79 cells. The effects of vanillin on H2O2-induced chromosome
      aberrations were also examined. Vanillin had a dose-dependent enhancing effect on
      EMS-induced cytotoxicity and 6TG-resistant mutations, when cells were
      simultaneously treated with vanillin. The post-treatment with vanillin during the
      mutation expression time of cells after treatment with EMS also showed an
      enhancement of the frequency of mutations induced by EMS. However, vanillin
      suppressed the cytotoxicity induced by H2O2 when cells were post-treated with
      vanillin after H2O2 treatment. Vanillin showed no change in the absence of
      activity of H2O2 to induce mutations. Post-treatment with vanillin also
      suppressed the chromosome aberrations induced by H2O2. The differential effects
      of vanillin were probably due to the quality of mutagen-induced DNA lesions and
      vanillin might influence at least two different kinds of cellular repair
      functions. The mechanisms by which vanillin enhances or suppresses chemical
      induced cytotoxicity, mutations and chromosome aberrations are discussed.

PMID- 1379330
TI  - Baseline frequency of sister-chromatid exchanges in 142 persons of the general
      Korean population.
AB  - Baseline frequencies of sister-chromatid exchange (SCE) were measured in
      lymphocytes of 142 healthy Koreans ranging in age from newborn infants to the
      fifties. The overall mean frequency of SCE was 8.78 +/- 0.24/cell. However,
      highly significant differences were found between individuals. The mean SCE
      values of the newborn babies and small children less than 10 years old were
      significantly lower than those of other age groups. No age effect was, however,
      observed in adolescent and adult subjects. Females had statistically higher SCE
      levels than males. The mean SCE frequencies of smokers, measured in male subjects
      more than 10 years old, were slightly, but statistically significantly, higher
      than those of non-smokers.

PMID- 1379331
TI  - An inhibitor of potentially lethal damage (PLD) repair reduces the frequency of
      gamma-ray-induced mutations in cultured Chinese hamster V79 cells.
AB  - Cordycepin (3'-deoxyadenosine, 3'-dA) is an RNA antimetabolite and a
      radiosensitizer in cultured mammalian cells. In the present paper, the effects of
      3'-dA on gamma-ray-induced lethality and 6-thioguanine (6TG)-resistant mutations
      in cultured Chinese hamster V79 cells were examined. 3'-dA had the effect of
      sensitizing the lethality induced by gamma-rays. The potentially lethal damage
      (PLD) repair produced by post-incubation of cells in Hanks' solution after gamma
      irradiation was almost completely suppressed by 5 x 10(-5) M 3'-dA. When cells
      were irradiated with 10 Gy gamma-rays and incubated with 3'-dA for 5 h, the
      frequency of 6TG-resistant mutations induced by gamma-rays decreased to one-sixth
      of that of irradiated cells incubated without 3'-dA. The decrease in the
      frequency of gamma-ray-induced mutations was dependent on the length of
      incubation time with 3'-dA. It is suggested that the inhibition of PLD repair by
      3'-dA may be that of error-prone repair.

PMID- 1379332
TI  - The in vivo and in vitro genotoxicity of aromatic amines in relationship to the
      genotoxicity of benzidine.
AB  - Benzidine and 12 related aromatic amines have been studied for the effects of
      substituent groups and pi orbital conjugation on their genotoxicity as measured
      by their mutagenicity in vitro with Salmonella and by chromosomal aberrations
      (CA) in vivo in the bone-marrow cells of mice. The in vitro studies indicated
      increases in mutagenicity with increases in the electron withdrawing ability of
      para' substituents. Mutagenicity also increases with increased conjugation as
      shown by the degree of planarity of the biphenyl compounds and by comparing the
      mutagenicities of biphenyl amines to stilbenes as well as to ethylene bridged
      diphenyl compounds. The relative in vitro mutagenicity results were not
      predictive of relative in vivo CA results. The 3 most genotoxic compounds in vivo
      were the conjugated amines without substituents in the para' position. The CA
      values for 4-aminostilbene were exceptionally high. These in vivo results
      indicate increased genotoxicity for benzidine analogs without substitution in the
      para' position.

PMID- 1379333
TI  - I-R hybrid dysgenesis in Drosophila melanogaster. Use of in situ hybridization to
      show the association of I factor DNA with induced sex-linked recessive lethals.
AB  - The purpose of this paper is the genetic visualization by in situ hybridization
      of 130 sex-linked recessive lethals plus a non-lethal induced by I-R dysgenesis.
      This collection of lethals involves inducer strains which differ in the position
      of the I elements on the X chromosomes. The I-R interaction was strong. Our
      previous results have shown that about 30% of the induced recessive lethals are
      associated with cytologically visible chromosomal rearrangements. (1) The
      rearrangements induced by I-R-type hybrid dysgenesis often exhibit homology with
      the I factor at the level of one or both junction points, depending on the types
      of chromosome rearrangements. These results suggest that the chromosome
      rearrangements arise directly from the transposition of I elements. However, the
      breakpoints of some types of cytologically non-visible deficiencies and of 2
      small cytologically visible deficiencies do not present detectable homology with
      the I factor. (2) The majority of rearrangements do not involve the I elements
      already present on the paternal X chromosome. (3) The hybridization signal
      distributions on the X chromosome are not uniform. They present peaks of various
      heights which may correspond to specific anchoring areas of copies of I in the
      course of integration. (4) The data presented here agree with the literature with
      respect to the mean number of copies of I per X chromosome and to the excess of
      copies of I at locus 1A. Two rearrangement formation mechanisms are envisaged:
      crossing-over and 'target' exchanges.

PMID- 1379334
TI  - Enhancing effect of heterocyclic amines and beta-carbolines on UV or chemically
      induced mutagenesis in E. coli.
AB  - Most heterocyclic amines and beta-carbolines--harman, norharman, harmine,
      harmaline--enhanced UVC (254 nm) induced mutagenesis without microsomal
      activation in E. coli B/r WP2. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P
      1) was most effective and increased UVAB (295-400 nm) induced mutations as well
      as UVC induced ones. Trp-P-1 enhanced the frequencies of mutations induced by not
      only UV but also 4-nitroquinoline-1-oxide (4NQO) or 2-(2-furyl)-3-(5-nitro-2
      furyl)acrylamide (AF2), while it showed little effect on N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) or gamma-ray induced mutagenesis. Trp-P-1 decreased the
      survival of UVC irradiated cells of CM571recA. However, these effects of Trp-P-1
      on UVC induced mutagenesis and lethality were not observed in WP2suvrA which is
      excision repair deficient. The alkaline sucrose gradient sedimentation analysis
      demonstrated that Trp-P-1 blocked the incision step in DNA excision repair.
      Further, pretreatment with Trp-P-1 before UVC irradiation showed no effect on UVC
      induced mutagenesis. Similar effects were also seen in the case of harman or
      norharman. These results suggest that heterocyclic amines and beta-carbolines
      inhibit DNA excision repair directly or indirectly, thus enhancing UV or
      chemically induced mutagenesis.

PMID- 1379335
TI  - Clastogenicity of low pH to various cultured mammalian cells.
AB  - It has been reported that low pH itself can be clastogenic to Chinese hamster
      ovary cells or mouse lymphoma L5178Y cells. On the other hand, there was no
      indication that low pH is clastogenic to rat or human lymphocytes. Therefore, in
      order to evaluate the generality of clastogenicity of low pH conditions,
      chromosomal aberration tests were carried out on Chinese hamster cell line cells
      (CHO-K1, CHL, Don and V79 379A) and human cells (HeLa and peripheral lymphocytes
      used as whole-blood cultures). The cytotoxicity of low pH to each cell line was
      also evaluated by counting surviving cells. The treatment medium used was Eagle's
      MEM containing 15 mM MES or Bis-Tris as an organic buffer to maintain the acidity
      of the medium for the 6-h or 24-h treatment period, and pH adjustment was done
      with NaOH or HCl. Chromosomal aberrations were induced at pH 6.5 or below in CHO
      or CHL cells, and the maximum frequency was 24.7% at pH 6.0 or 34% at pH 6.3,
      respectively. About 5-10% of Don or HeLa cells had aberrations over the range of
      pH 6.6-6.0 or pH 6.6-6.3, respectively. In V79 379A cells or human lymphocytes,
      however, aberrant cells amounted to about 8% at near pH 6.0, where cell survival
      was low (less than 20%). About 90% of aberrations induced in each cell line
      examined were chromatid-type gaps and breaks. When CHO or CHL cells were treated
      with acidic medium for 6 h plus 18 h recovery in fresh medium, about 20% of cells
      had aberrations including chromatid exchanges at pH 5.5 or pH 5.7, respectively.
      These results indicate that clastogenicity of low pH is a general finding,
      although the extent of it varies with cell type, and that the clastogenicity is
      associated with varying extents of cytotoxicity. The mechanisms of clastogenesis
      at low pH are not known, but might involve inhibition of DNA or protein synthesis
      or DNA-repair enzymes.

PMID- 1379336
TI  - Effect of hepatic cytochrome P-450 inducing agents on mutagen activity in the
      host-mediated assay.
AB  - Intraperitoneal treatment of female BALB/c mice with either phenobarbitone or
      beta-naphthoflavone led to the induction of various hepatic enzymes associated
      with xenobiotic metabolism and to increased abilities of hepatic S9 fractions to
      convert the dietary carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
      (MeIQx) to an active bacterial mutagen. In the case of another carcinogen,
      aflatoxin B1 an increase in in vitro hepatic activation was seen only in mice
      treated with phenobarbitone. In contrast, pretreatment with either phenobarbitone
      or beta-naphthoflavone reduced the in vivo activity of both aflatoxin B1 and
      MeIQx in the host mediated bacterial mutation assay. These data indicate that,
      for some carcinogens at least, the host-mediated assay may be used to predict the
      carcinogenic consequences of hepatic enzyme induction.

PMID- 1379337
TI  - Structure-activity relationships for unsaturated dialdehydes. 6. The mutagenic
      activity of 11 compounds in the V79/HGPRT assay.
AB  - The mutagenic activity of 11 sesquiterpenoid unsaturated dialdehydes in the
      V79/HGPRT assay has been determined, and is compared with previously published
      data on the mutagenicity of the same compounds towards Ames Salmonella strains.
      One compound, isovelleral, is a potent mutagen in both assays, while six
      compounds, which are positive in the Ames Salmonella/microsome assay, show no
      significant activity in this study. One compound, acetylmerulidial, is negative
      in the Ames Salmonella/microsome assay but significantly although weakly
      mutagenic in the V79/HGPRT assay. The remaining three compounds are inactive in
      both assays. The study is part of a general investigation of quantitative
      structure-activity relationships for unsaturated dialdehydes, a class of natural
      occurring compounds known for their potent and numerous biological activities.

PMID- 1379338
TI  - Induction of external abnormalities in offspring of male mice irradiated with
      252Cf neutron.
AB  - To assess the genetic effects of fission neutron, the induction of external
      malformations was studied in F1 fetuses after F0 male mice were irradiated. Male
      mice of the ICR:MCH strain were irradiated with 252Cf neutron at doses of 0.238,
      0.475, 0.95 and 1.9 Gy. They were mated with non-irradiated female mice at 71-120
      days after the irradiation. Pregnant females were autopsied on day 18 of
      gestation and their fetuses were examined for deaths and external abnormalities.
      No increases of pre- and post-implantation losses were noted at any dose.
      External abnormalities were observed at rates of 1.40% in the 0.238 Gy, 2.23% in
      the 0.475 Gy, 3.36% in the 0.95 Gy and 3.26% in the 1.9 Gy groups; the rate in
      the control group was 1.65%. The dose-response curve was linear up to 0.95 Gy,
      and then flattened out; the induction rate of external abnormalities was 2.7 x
      10(-4)/gamete/cGy based on the linear regression. These results indicated that
      fission neutron effectively induces external abnormalities in F1 fetuses after
      spermatogonial irradiation.

PMID- 1379339
TI  - Gender differences and the interpretation of genetic instability in Alzheimer's
      disease.
AB  - The neuronal degeneration and death which characterize Alzheimer's disease (AD)
      may stem from a constitutive genetic instability related to DNA repair deficits.
      To test this hypothesis, we treated peripheral blood lymphocytes from persons
      with AD, age-matched controls, and young controls with two drugs that induce
      chromosome breakage. Bleomycin, a radiomimetic antineoplastic drug, causes single
      and double-stranded DNA breaks through the generation of activated oxygen
      radicals. Methyl methane-sulfonate (MMS) is a monofunctional alkylating agent
      that binds covalently to DNA. Cells were grown in culture for 72 h, with drug
      treatments for 4 h (bleomycin) or 24 h (MMS) prior to harvest. Fifty cells per
      subject per drug were scored for chromosome breakage. Breakage rates for both
      drugs in AD women were significantly higher than those in age-matched control
      women. This was not the case in men, due to the very high induced breakage rates
      seen in the age-matched normal control men. Because the induced breakage rates in
      AD women and AD men are equivalent, it seems likely that an independent factor
      may be contributing to genetic instability in the normal control men. Our
      findings indicate that the interpretation of the response of AD lymphocyte
      chromosomes to DNA-damaging chemicals can be strongly confounded by the effects
      of gender ratio in the control population sampled. These findings have important
      implications for the design of future studies of Alzheimer's disease, as well as
      for the assessment of health risks in unaffected elderly populations.

PMID- 1379340
TI  - Enhancement of oxidative DNA degradation by histidine: the role of stereochemical
      parameters.
AB  - The nicking of supercoiled DNA by H2O2 and ferrous iron has been studied in a
      variety of environmental conditions. The replicative form of phage fd DNA (fd RF
      DNA) was used for investigating the phenomenon. The rate of nicking was measured
      in 10 mM NaCl. The addition of 1 mM Tris-HCl buffer (pH 7.5) slowed down the rate
      of nicking, the addition of 0.1 mM histidine enhanced it. The simultaneous
      presence of 1 mM Tris-HCl buffer and of 0.1 mM histidine further enhanced the
      rate of nicking of fd RF DNA. Increasing the concentration of NaCl dramatically
      reduced the rate of the reaction. The degradation of fd RF DNA was determined as
      a function of the concentration of histidine (0-5 mM): the rate increases with
      concentration, reaches a maximum and then decreases. In the presence of
      histidine, increasing the concentration of Tris leads to a similar phenomenon. In
      the absence of histidine, Tris always quenches the degradation of DNA. Electron
      spin resonance measurements failed to detect an enhancement of the signal
      characteristic for the hydroxyl radical when histidine was added to the solution
      containing hydrogen peroxide and ferrous iron. When the nicking of DNA is
      achieved via the process of auto-oxidation of ferrous iron (i.e., in the absence
      of added H2O2), histidine only reduces the rate of reaction in a dose-dependent
      manner, in the explored range of concentrations. In the presence of H2O2 and
      ferrous iron, histidine enhances the rate of nicking of double-stranded DNA in
      its supercoiled as well as in its relaxed state, but fails to modify the rate of
      nicking of fd DNA when it is in its vegetative, single-stranded form.

PMID- 1379341
TI  - The accident at Chernobyl and trisomy 21 in Finland.
AB  - Our objective was to explore whether the radiation fallout in Finland after the
      accident at the Chernobyl nuclear power plant in April 1986 led to an increased
      incidence of trisomy 21. In this geographic and temporal cohort study, the
      country was divided into three zones according to the amounts of radioactive
      fallout and internal radiation caused by two cesium isotopes. The 518
      cytologically verified cases of trisomy 21 were divided into a control group
      (conceived before the accident), and a study group of children whose expected
      dates of birth were in the post-accident years 1987-1988, i.e., pregnancies
      commenced after May 1986. The cases were also divided into three subgroups
      according to the zones of radiation. There were no significant differences in
      prevalence of trisomy 21 between the control and study groups nor between the
      three zones in spite of the significant differences in the levels of radiation
      and in the body burden that prevailed throughout the study period. Power
      estimates showed that in the two zones of lower radiation, an increase of 0.5% in
      the prevalence would have been detected with a power of 0.85, and in the somewhat
      smaller zone of the highest radiation, with a power of 0.70. The study lends no
      further support to the view that the low radiation fallout in western Europe
      would have been causally associated with trisomy 21.

PMID- 1379342
TI  - Reduced 5-hydroxymethyluracil-DNA glycosylase activity in Werner's syndrome
      cells.
AB  - Werner's syndrome (WS) is an autosomal recessive disease marked by early symptoms
      of accelerated aging. There is evidence indicating accumulation of oxidized DNA
      bases to be a major factor in cellular aging. The first step of excision repair
      of such bases in human cells is their removal from DNA by glycosylases. 5
      Hydroxymethyluracil (HMU)-DNA glycosylase excises HMU from DNA; another
      glycosylase removes many non-aromatic pyrimidine derivatives. Levels of
      glycosylases that excise oxidized pyrimidines from DNA were compared between
      confluent and proliferating populations of WS cells, age-matched controls, and
      young control cells. They were assayed by measurements of direct release of free
      bases from their respective DNA substrates. Specific activities of the
      glycosylase that releases various modified pyrimidines and of uracil-DNA
      glycosylase (which removes uracil from DNA) were essentially the same in all cell
      lines. Cell cycle variations of these enzymes also did not differ between WS and
      control cells. HMU-DNA glycosylase specific activity was reduced in WS cells.
      Reduction of HMU-DNA glycosylase has been described in senescent human WI-38
      cells. Therefore, while neither WS nor senescent cells have overall deficiencies
      of DNA glycosylase activities, they both might have reduced excision of HMU from
      DNA. This indicates a possible role of HMU accumulation in the aging process.

PMID- 1379343
TI  - Effect of neonatal exposure to 5-bromo-2'-deoxyuridine on life span, estrus
      function and tumor development in rats--an argument in favor of the mutation
      theory of aging?
AB  - Outbred LIO rats were exposed to subcutaneous injections (3.2 mg) of a synthetic
      analogue of thymidine, 5-bromo-2'-deoxyuridine (BrdUrd), on days 1 and 3, or days
      1, 3, 7 and 21 of postnatal life. The mean life span decreased by 31% and 38% in
      male and by 14% and 27% in female rats that received 2 and 4 injections of
      BrdUrd, respectively, in comparison to untreated controls. The opening of the
      vagina was delayed, whereas age-related changes in the length of the estrous
      cycle and in the incidence of persistent estrus and/or anestrus were observed
      earlier in BrdUrd-injected female rats than in untreated ones. Inhibition of
      compensatory ovarian hypertrophy induced by hemiovariectomy at the age of 3
      months was found in females exposed neonatally to BrdUrd as compared to untreated
      rats, while the uterus weight increase induced by the administration of human
      chorionic gonadotropin was similar in both control and BrdUrd-treated infantile
      rats. These data suggest that exposure to BrdUrd in early life impairs pituitary
      gonadotropic function in female rats. It was also shown that neonatal
      administration of BrdUrd to rats doubles the incidence of chromosome aberrations
      in peripheral blood lymphocytes in comparison to controls and is followed by a
      dose-related increase in tumor incidence. Our observations on the decrease in
      mean and maximum life span, acceleration of age-related changes in reproductive
      system function, increase in chromosome aberration and tumor incidence and
      decrease in tumor latency in rats exposed to BrdUrd in early life suggest that
      this model could be used as a model of accelerated aging and that some of the
      results can be interpreted as arguments in favor of the mutation theory of aging.

PMID- 1379344
TI  - Prenatal screening for Down's syndrome with use of maternal serum markers.
AB  - BACKGROUND: Approximately 35 percent of all cases of Down's syndrome in fetuses
      can be detected by measuring maternal serum alpha-fetoprotein during the second
      trimester in the general population of pregnant women. Recent case-control
      studies indicate that this detection rate could be approximately doubled by
      measuring serum levels of unconjugated estriol and chorionic gonadotropin, which
      are abnormally low and abnormally high, respectively, in women carrying fetuses
      affected by Down's syndrome. METHODS: We prospectively screened 25,207 women and
      adolescents in the second trimester of pregnancy and assigned each a risk of
      fetal Down's syndrome with an algorithm that took into account measurements of
      all three serum markers in combination with maternal age. On this basis, 1661
      subjects (6.6 percent) were initially assigned a second-trimester risk of fetal
      Down's syndrome of at least 1 in 190, and 962 (3.8 percent) were offered
      amniocentesis for chromosomal analysis after verification of gestational age.
      Gestational age was determined on the basis of the first day of the last
      menstrual period or, when available, by ultrasonography. RESULTS: Among the 760
      women and adolescents who chose amniocentesis, 20 cases of fetal Down's syndrome
      were detected, along with 7 other chromosomal disorders. There was 1 additional
      case of fetal Down's syndrome among the 202 women who chose not to have
      amniocentesis. The rate of detection of Down's syndrome was thus 58 percent (21
      of 36 expected cases), and the frequency of identifying a fetus with Down's
      syndrome in women undergoing amniocentesis was 1 per 38 amniocenteses (95 percent
      confidence interval, 1 in 25 to 1 in 62). CONCLUSIONS: Measuring serum alpha
      fetoprotein, chorionic gonadotropin, and estriol is more effective in screening
      for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone.
      Such an expanded protocol can readily be incorporated into existing prenatal
      screening programs.

PMID- 1379345
TI  - Antisense oligodeoxynucleotides to GS protein alpha-subunit sequence accelerate
      differentiation of fibroblasts to adipocytes.
AB  - Fully-differentiated mouse 3T3-L1 fibroblasts accumulate large amounts of lipid
      at 7-10 days after induction by insulin or by dexamethasone and a methyl
      xanthine. G proteins mediate transmembrane signalling from a diverse group of
      cell-surface receptors to effector units that include phospholipase C, adenylyl
      cyclase and ion channels. They are also targets of regulation themselves. 3T3-L1
      fibroblasts display marked changes in levels of G protein when induced to
      differentiate to adipocytes. Here we show that cholera toxin, which ADP
      ribosylates and activates the G protein subunit Gs alpha, blocks the induction of
      differentiation, whereas increasing intracellular cyclic AMP directly with the
      dibutyryl analogue or indirectly with pertussis toxin or forskolin does not
      affect differentiation. Oligodeoxynucleotides antisense to the sequence encoding
      Gs alpha accelerate differentiation markedly. The time course of adipogenesis
      declined from 7-10 days in controls to roughly 3 days in cultures treated with
      antisense-Gs alpha oligodeoxynucleotides, whereas oligodeoxynucleotides,
      antisense to Gi alpha 1, Gi alpha 3, and sense and missense to Gs alpha, had no
      such effect. Antisense-Gs alpha alone induced differentiation by day 7,
      indicating that Gs alpha activity modulates differentiation in 3T3-L1 cells,
      acting in a new role which is independent of increased intracellular cAMP.

PMID- 1379347
TI  - A single point mutation is the cause of the Greek form of hereditary persistence
      of fetal haemoglobin.
AB  - In normal humans the fetal stage-specific gamma-globin genes are silenced after
      birth and not expressed in the adult. Exceptions are seen in cases of hereditary
      persistence of fetal haemoglobin (HPFH). These are clinically important because
      the elevated levels of gamma-globin can alleviate beta-thalassaemia and sickle
      cell anaemia. One class of mutations is associated with point mutations in the
      promoter of the gamma-globin genes (non-deletion HPFH), whereas others seem to be
      caused by large deletions 3' to the gamma-globin genes. To test whether the point
      mutation found in the Greek non-deletion HPFH (guanine to adenine at nucleotide
      position -117) is the cause of the raised gamma-globin levels in the adult stage
      and is not just a linked polymorphism, we engineered this mutation into a gamma
      globin gene. When this gene was introduced into mice, the presence of the -117
      mutation results in persistence of gamma-globin expression at a high level and a
      concomitant decrease in beta-globin expression in fetal and adult mice. We show
      that these changes correlate with the loss of binding of the transcription factor
      GATA1 to the gamma-globin promoter, suggesting that it may act as a negative
      regulator of the gamma-globin gene in adults.

PMID- 1379346
TI  - Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor for Ras
      p21.
AB  - The stimulation of a variety of cell surface receptors promotes the accumulation
      of the active, GTP-bound form of Ras proteins in cells. This is a critical step
      in signal transduction because inhibition of Ras activation by anti-Ras
      antibodies or dominant inhibitory Ras mutants blocks many of the effects of these
      receptors on cellular function. To reach the active GTP-bound state, Ras proteins
      must first release bound GDP. This rate-limiting step in GTP binding is thought
      to be catalysed by a guanine-nucleotide-releasing factor (GRF). Here we report
      the cloning of complementary DNAs from a rat brain library that encode a
      approximately 140K GRF for Ras p21 (p140Ras-GRF). Its carboxy-terminal region is
      similar to that of CDC25, a GRF for Saccharomyces cerevisiae RAS. This portion of
      Ras-GRF accelerated the release of GDP from RasH and RasN p21 in vitro, but not
      from the related RalA, or CDC42Hs GTP-binding proteins. A region in the amino
      terminal end of Ras-GRF is similar to both the human breakpoint cluster protein,
      Bcr, and the dbl oncogene product, a guanine-nucleotide-releasing factor for
      CDC42Hs. An understanding of Ras-GRF function will enhance our knowledge of the
      many signal transduction pathways mediated by Ras proteins.

PMID- 1379348
TI  - [Mechanism of action of the new immunosuppressants: cyclosporin A, FK 506 and
      rapamycin].

PMID- 1379350
TI  - Anterior choroidal artery syndrome after surgery for internal carotid artery
      aneurysms.
AB  - We report five patients with anterior choroidal artery syndrome after surgery for
      internal carotid artery aneurysms. All patients suffered hemiparesis, and
      hemisensory loss and homonymous hemianopsia were identified in 2 patients. The
      characteristic triad of the syndrome was recognized in only 1 patient. Dominant
      and nondominant cerebral hemisphere signs have been reported in association with
      this syndrome, and 2 patients had a speech disturbance in our series. In previous
      reports, neurological deficits were mild and patient prognosis was good in
      anterior choroidal artery infarct, in spite of the fact that the artery supplied
      the corticobulbar and corticospinal tracts. This report suggests the possible
      causes of this syndrome after surgery for internal carotid aneurysms, which
      involve vasospasm after subarachnoid hemorrhage, mechanical obstruction,
      thromboembolism, and distortion of the aneurysm clip.

PMID- 1379349
TI  - Specific [3H]raclopride binding to neostriatal dopamine D2 receptors: role of
      disulfide and sulfhydryl groups.
AB  - Receptor binding studies were performed in rabbit neostriatum (caudate-putamen)
      using the dopamine D2 antagonist [3H]raclopride. Treatment of the membrane
      preparations with the reducing agent L-dithiothreitol (L-DTT) as well as with the
      alkylating compound N-ethylmaleimide (NEM), produced dose-dependent decreases of
      specific [3H]raclopride binding; the IC50 values were of 3.1 and 1.2 mM,
      respectively. Saturation experiments showed that the reduction of disulfide (-S-S
      ) bonds by L-DTT (1 mM) decreased the number of binding sites, with only a slight
      increase in the affinity. On the other hand, alkylation of sulfhydryl (-SH)
      groups by NEM (1 mM) decreased both receptor number and affinity. The properties
      of the remaining binding sites were examined in competition curves with the
      physiological substrate dopamine and the dopaminergic antagonist (+)butaclamol.
      The IC50 values for (+)butaclamol in control and in L-DTT and NEM treated
      membranes were between 3.4 and 4.8 nM, with Hill coefficients (nH) of 1,
      indicating that the remaining binding sites conserved a high affinity for
      antagonist binding. In the case of dopamine, the curves were shallow (nH 0.45
      0.64) and both compounds increased the IC50 from 0.7 microM (control) to 8 microM
      and 11 microM, for L-DTT and NEM respectively. Iterative analysis revealed that L
      DTT produced a very important (greater than 60%) decrease in the number of high
      affinity (RH) binding. After NEM, there was a decrease in both the number of (RH)
      and the affinity (KH) of the high-affinity binding sites, and in the affinity
      (KL) of the low-affinity sites. These results demonstrate the participation of -S
      S- and -SH groups in the agonist conformation of the primary ligand recognition
      site of the dopamine D2 receptor. Alternatively, -S-S- and -SH groups could be
      related to the coupling of the primary ligand recognition protein with adenylate
      cyclase by means of an inhibitory type of G protein.

PMID- 1379351
TI  - Optic aphasia with spared action naming: a description and possible loci of
      impairment.
AB  - A brief functional description is given of an optic aphasic patient, A.G., who
      shows a pure and isolated deficit in naming visually presented objects on
      confrontation, but with sparing of visual action names. We show how some tasks
      related to imagery are compromised in this patient and speculate on possible
      functional site(s) of impairment in terms of the routes from perception to
      naming. We suggest why action naming may be spared in such cases.

PMID- 1379353
TI  - The distribution of binding by isolectin I-B4 from Griffonia simplicifolia in the
      trigeminal ganglion and brainstem trigeminal nuclei in the rat.
AB  - The distribution of binding by the isolectin I-B4 from Griffonia simplicifolia in
      the rat trigeminal system has been investigated. This lectin binds to a sub
      population of small-diameter trigeminal ganglion neurons. Double-labelling
      studies revealed that this lectin bound to all the trigeminal ganglion neurons
      containing somatostatin, whereas it bound to less than 25% of those containing
      calcitonin gene-related peptide or substance P. In the brainstem this lectin gave
      terminal-like staining in only the sub-nucleus caudalis of the trigeminal nuclei.
      In this nucleus, staining was most dense in the inner part of lamina II.
      Morphometric studies suggest that this lectin and that from the soybean recognize
      the same population of cells. The relationship of this data to those obtained in
      other studies using markers binding to glycoconjugates with a terminal alpha
      galactose is discussed.

PMID- 1379352
TI  - L-glutamate-evoked release of dopamine from synaptosomes of the rat striatum:
      involvement of AMPA and N-methyl-D-aspartate receptors.
AB  - Previously, using purified synaptosomes from the rat striatum, we have shown that
      agonists of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)
      receptors stimulate the release of [3H]dopamine continuously synthesized from
      [3H]tyrosine. Similar results were obtained with N-methyl-D-aspartate in the
      absence of magnesium. In the present study, using the same approach, attempts
      were made to determine whether in the presence of magnesium, the combined
      stimulation of AMPA receptors allows us to demonstrate the presynaptic
      facilitation of [3H]dopamine release through N-methyl-D-aspartate receptors. L
      Glutamate (10(-3) M) markedly stimulated the release of [3H]dopamine from
      synaptosomes, this effect being about twice that found with AMPA (10(-3) M) while
      N-methyl-D-aspartate (10(-3) M) even in the presence of glycine (10(-6) M) was
      ineffective. In agreement with previous results, a stimulatory effect of N-methyl
      D-aspartate and glycine was only observed in the absence of magnesium. This
      response was blocked by 6,7-dinitro-quinoxaline-2,3-dione (3 x 10(-5) M),
      confirming that this compound, generally used as an AMPA antagonist, also blocks
      N-methyl-D-aspartate receptors. The AMPA (10(-3) M)-evoked release of
      [3H]dopamine was markedly potentiated by the combined application of N-methyl-D
      aspartate (10(-3) M) and glycine (10(-6) M) in the presence of strychnine,
      indicating that the concomitant activation of AMPA receptors removes the voltage
      dependent magnesium block of N-methyl-D-aspartate receptors.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1379354
TI  - Guanethidine sympathectomy of mature rats leads to increases in calcitonin gene
      related peptide and vasoactive intestinal polypeptide-containing nerves.
AB  - Changes in the innervation of the heart (right atrium), mesenteric blood vessels,
      vas deferens and superior cervical ganglia have been examined following long-term
      sympathectomy of the mature rat. Patterns of innervation were investigated by
      histochemical and immunohistochemical techniques, while levels of noradrenaline
      and neuropeptides were measured by neurochemical assays. Large doses of
      guanethidine (80 mg/kg) were given daily for four weeks to 12-14 week-old male
      rats which were killed at 18-20 weeks of age. Catecholamine-containing nerves
      were severely depleted or absent in all tissues, together with a reduction in
      noradrenaline content. Neuropeptide Y levels were depleted by 97% in vas
      deferens, 78% in mesenteric vein and 50% in right atrium and superior cervical
      ganglion. Increases in levels of calcitonin gene-related peptide were seen in the
      mesenteric vein (up seven-fold), superior cervical ganglia (up 11-fold) and vas
      deferens (prostatic portion up three-fold), which were also evident by assessment
      of immunolabelling of nerve fibres. Calcitonin gene-related peptide levels were
      not increased in the right atrium. In addition, an increase in vasoactive
      intestinal polypeptide-immunoreactive nerve fibre density was seen in the
      mesenteric artery and vas deferens, although no significant differences were
      observed in assays of vasoactive intestinal peptide levels in any tissue. No
      changes were seen in the innervation of any of the tissues by substance P
      immunoreactive nerve fibres either by immunohistochemical or immunochemical assay
      assessment. This study indicates that there are selective changes in the mature
      nervous system in response to the loss of sympathetic nerves. Differences between
      these changes and the response of the developing nervous system to long-term
      sympathectomy are discussed.

PMID- 1379355
TI  - The co-existence of biogenic amines and neuropeptides in the type I cells of the
      cat carotid body.
AB  - The mammalian carotid body consists of preneural type I (glomus) cells
      synaptically coupled to afferent axon terminals and enveloped by type II
      (sustentacular) cells. Recent studies indicate the presence of multiple putative
      neurotransmitters in this arterial chemoreceptor organ. A double-labeling
      immunocytochemical technique was utilized which allows simultaneous visualization
      of two neurochemicals in a single cell. The issue of transmitter co-occurrence in
      type I cells of the cat carotid body was addressed using specific antibodies for
      seven neurochemical agents: tyrosine hydroxylase, dopamine-beta-hydroxylase,
      choline acetyltransferase, serotonin, substance P, met-enkephalin and
      chromogranin. A high degree (greater than 70%) of co-localization was observed
      for most pairs of markers, indicating the co-existence of multiple neuroactive
      agents in type I cells of the cat carotid body. The intensity of staining varied
      greatly among cells but formed a pattern. Thus, for tyrosine hydroxylase and
      dopamine-beta-hydroxylase, the majority of double-labeled type I cells exhibited
      equivalently low or high levels of both, while for the neuropeptides unequal
      levels of the two markers predominated. Neuropeptides also co-existed in type I
      cells with catecholamine-synthesizing enzymes and with serotonin. The functional
      significance of such patterns of multiple co-existence involving biogenic amines
      and neuropeptides is discussed. Our results indicate a high degree of co
      occurrence of reaction product for amine-synthesizing enzymes (tyrosine
      hydroxylase, dopamine-beta-hydroxylase and choline acetyltransferase), the
      indoleamine serotonin, and the neuropeptides substance P and met-enkephalin.

PMID- 1379356
TI  - Linkage analysis of candidate loci in autosomal dominant myotonia congenita.
AB  - Electrophysiologic studies in patients with autosomal dominant myotonia congenita
      (ADMC) have implicated defects of both muscle membrane sodium and chloride
      channels. An adult skeletal muscle sodium channel (ASkM1) gene maps to chromosome
      17q23-25, and defects in this gene are almost certainly responsible for at least
      three variants of hyperkalemic periodic paralysis (HPP)--myotonic HPP,
      nonmyotonic HPP, and paramyotonia congenita. A gene for a muscle chloride channel
      has not yet been mapped in humans, but has been identified in the mouse. The gene
      for the cystic fibrosis transmembrane regulator (CFTR), which has chloride
      channel properties, is located on chromosome 7q31. This region is syntenic with
      the area of mouse chromosome 6 that contains the muscle chloride channel gene, a
      defect in which is responsible for the ADR phenotype, a murine model of myotonia.
      We performed linkage analysis using chromosome 17q polymorphisms at D17S74,
      SCN4A, and GH1, two chromosome 7q31 restriction fragment length polymorphisms,
      and a dinucleotide repeat polymorphism within the CFTR gene (CFTR-DNR), in three
      pedigrees with ADMC. The lod scores obtained show that the locus for ADMC is not
      at ASkM1 and is excluded from a region of at least 24 cM on either side of the
      CFTR gene.

PMID- 1379357
TI  - Acute pancreatitis in children with anticholinesterase insecticide intoxication.
AB  - Gastrointestinal symptoms are commonly seen in anticholinesterase insecticide
      intoxication. A few studies in adults have demonstrated some evidence for
      pancreatic damage in this poisoning. To see whether this association exists also
      in children, we conducted a prospective study in 17 consecutive children with
      typical organophosphate and carbamate poisoning. On admission and following
      recovery, serum amylase, immunoreactive trypsin, glucose, calcium, urea,
      creatinine, and arterial blood gas values were determined and compared with those
      of age-matched control subjects. Acute pancreatitis was diagnosed in 5 subjects.
      They demonstrated significantly elevated (greater than mean + 2 SD) serum levels
      of both immunoreactive trypsin (914.0 +/- 317.4 ng/mL, 159.9 +/- 36.4 ng/mL, and
      169.7 +/- 41.2 ng/mL, respectively; P less than .01) and amylase (448.0 +/- 264.4
      U/L, 152.8 +/- 90.9 U/L, and 56.8 +/- 26.3 U/L, respectively; P less than .001; n
      = 4), compared with other patients and control subjects. Gastrointestinal
      symptoms were noted in all 5 subjects, with severe abdominal pain in 2. Such
      symptoms were evident in only 41% of the other 12 patients. Serum glucose levels
      were significantly elevated in these subjects compared with others (389.0 +/-
      66.2 mg/100 mL vs 180.4 +/- 72.3 mg/100 mL; P less than .01). None had
      hypocalcemia, renal dysfunction, or acidosis. All had complete recovery. It is
      concluded that acute pancreatitis is probably not rare in children with
      anticholinesterase insecticide poisoning. This may contribute to the development
      of gastrointestinal symptoms and hyperglycemia often observed in these patients.

PMID- 1379358
TI  - Palliative treatment of hyperinsulinism with cyproheptadine and diazoxide.
AB  - Treatment for hyperinsulinism in infants and children can be difficult and has
      included numerous treatment modalities. This paper reports 16 months of
      palliative treatment with cyproheptadine and diazoxide in a child with
      hyperinsulinism initially diagnosed at 6 months of age (her insulin level was 80
      microU/mL while her glucose level was 38 mg/dL). She continued to have episodes
      of staring and alteration in level of consciousness while receiving her usual
      doses of diazoxide (12 mg/kg) alone. Mean nocturnal glucose values, which were
      quite low during treatment with diazoxide alone, improved significantly with the
      addition of cyproheptadine to her therapeutic regimen. Fasted C-peptide values,
      elevated during diazoxide alone, returned to the normal range with combination
      treatment for 16 months. Cyproheptadine and diazoxide in combination may be
      useful for treatment of hyperinsulinism that presents after the neonatal period.

PMID- 1379359
TI  - Ty1-copia group retrotransposons are ubiquitous and heterogeneous in higher
      plants.
AB  - We have used the polymerase chain reaction to isolate fragments of Ty1-copia
      group retrotransposons from a wide variety of members of the higher plant
      kingdom. 56 out of 57 species tested generate an amplified fragment of the size
      expected for reverse transcriptase fragments of Ty1-copia group retrotransposons.
      Sequence analysis of subclones shows that the PCR fragments display varying
      degrees of sequence heterogeneity. Sequence heterogeneity therefore seems a
      general property of Ty1-copia group retrotransposons of higher plants, in
      contrast to the limited diversity seen in retrotransposons of Saccharomyces
      cerevisiae and Drosophila melanogaster. Phylogenetic analysis of all these
      sequences shows, with some significant exceptions, that the degree of sequence
      divergence in the retrotransposon populations between any pair of species is
      proportional to the evolutionary distance between those species. This implies
      that sequence divergence during vertical transmission of Ty1-copia group
      retrotransposons within plant lineages has been a major factor in the evolution
      of Ty1-copia group retrotransposons in higher plants. Additionally, we suggest
      that horizontal transmission of this transposon group between different species
      has also played a role in this process.

PMID- 1379360
TI  - A new cluster of three tRNA genes in Pseudomonas aeruginosa.

PMID- 1379361
TI  - Solubilization in formamide protects RNA from degradation.

PMID- 1379362
TI  - Cellular differentiation in prostatic explant cultures: assessed by electron
      microscopy and X-ray microanalysis.
AB  - A method developed for X-ray microanalysis (XRMA) of cell monolayers cultured on
      Formvar film has been shown to be well suited for the study of explant cultures
      of human prostate. Adherence and epithelial cell outgrowth occur as readily on
      the formvar as on ordinary tissue culture plastic, giving rise to cultures with
      the same morphological characteristics. Conventional transmission electron
      microscopy revealed intracytoplasmic granules with the appearance of secretory
      vesicles. XRMA of electron-dense intracytoplasmic granules in freeze-dried
      cryosections showed significant local sequestration of calcium, but not of
      magnesium or zinc, elements that have previously been shown to colocalize with
      calcium in secretory granules in vivo. It is concluded that some aspects of the
      secretory phenotype are supported in this in vitro model. The factors regulating
      the expression of a differentiated phenotype in prostatic epithelium await
      further elucidation. XRMA may be useful in assessing the effects on secretory
      differentiation induced by variations in the culture conditions.

PMID- 1379364
TI  - Pathological and clinical associations of Ki-67 defined growth fractions in human
      prostatic carcinoma.
AB  - Estimation of the growth fraction of 153 prostatic carcinoma specimens employing
      Ki-67 immunostaining was undertaken and its relationship to various clinical
      parameters investigated. In prostate specimens, the percentage of tumour nuclei
      expressing Ki-67 antigen was measured and assigned a Ki-67 score. It was observed
      that high Ki-67 scores were associated with the poorly differentiated tumours,
      the correlation of this proliferation marker with histological grade was found to
      be significant (P less than 0.001). No relationship was observed between the Ki
      67 score of the primary tumour with either the patient's age or with the primary
      tumor stage (T category). The metastatic status of the patient at diagnosis and
      the Ki-67 score of the tumour were correlated (P less than 0.05), higher Ki-67
      scores being associated with M1 disease. Life-table analysis of 86 patients who
      subsequently received androgen withdrawal therapy, was undertaken with reference
      to the various Ki-67 scores of their primary tumors. A statistically significant
      difference in survival times was observed in patients whose Ki-67 values were
      less than 1% (P less than 0.0001) when compared to those patients whose tumours
      expressed 1% and over Ki-67 positivity, the former having longer survival times.
      When patients were subdivided according to their metastatic status and similar
      life-table analyses were carried out, no statistical difference was found between
      survival times and Ki-67 scores in M0 staged patients. In the M1 population of
      patients, however, those patients whose tumours were negative for Ki-67
      expression had significantly longer survival times than those patients whose
      tumours exhibited positive Ki-67 staining (P less than 0.01). Comparing M1 staged
      patients whose prostate tumor cells exhibited less than 1% Ki-67 positive nuclei
      with M1 staged patients whose prostate tumour cells contained 1% and higher Ki-67
      stained nuclei, a significantly longer survival time was found in the former
      group of patients (P approximately 0.0001).

PMID- 1379363
TI  - Hormonal regulation of prostate-specific antigen (PSA) glycoprotein in the human
      prostatic adenocarcinoma cell line, LNCaP.
AB  - Prostate-specific antigen (PSA) has emerged as the most useful marker for
      management of patients with prostate cancer. The regulation of this glycoprotein
      in vivo has important clinical implications. Indirect evidence indicates that the
      PSA glycoprotein might be regulated by androgens, and previous studies in this
      laboratory have demonstrated that PSA mRNA is upregulated by androgens. The
      current work reports a detailed study of PSA glycoprotein expression as
      influenced by steroid hormones in a human prostatic adenocarcinoma cell line,
      LNCaP. First, we have examined the steroid binding specificity of the androgen
      receptor in this cell line. In comparison with wild-type rat androgen receptor in
      prostate, the receptor in LNCaP cells has altered affinity for a number of
      steroids or analogs such as progesterone (R5020), antiprogesterone (RU486), two
      antiandrogens (cyperoterone acetate and hydroxyflutamide), and an androgen
      metabolite (epitestosterone). However, its affinity for androgens (mibolerone,
      dihydrotestosterone, and testosterone) is not changed. The receptor does not bind
      to the synthetic glucocorticoids (triaminolone acetonide and dexamethasone) nor
      to a synthetic estrogen DES (diethylstilbestrol). The change of the steroid
      binding specificity of the receptor is correlated with a single mutation (A----G
      at nucleotide #876 relative to the initiation codon) of the steroid binding
      domain of the receptor. The mutation and alteration of steroid-binding
      specificity of the androgen receptor is also correlated with PSA glycoprotein
      expression affected by different ligands tested. We have demonstrated that the
      PSA glycoprotein is upregulated by androgens and is affected by neither epidermal
      growth factor nor basic fibroblast growth factor. Moreover, PSA glycoprotein
      could be induced by R5020, estradiol, and epitestosterone; but neither
      glucocorticoids nor DES had any effect on PSA induction. Interestingly, although
      the antiandrogen, cyperotone acetate, had the ability to induce PSA, both RU486
      and hydroxyflutamide could block androgen and progesterone induction of PSA
      glycoprotein. Therefore, we conclude that the PSA glycoprotein expression is
      influenced predominantly by androgens via its receptor, and the mutation of the
      receptor can affect the expression of this cellular gene by the steroids other
      than androgens.

PMID- 1379365
TI  - [The role of glycosphingolipids in the expression of neoplastic phenotype. II.
      Glycosphingolipids of neoplastic cells and the immune system of the host].

PMID- 1379366
TI  - Carbachol does not down-regulate substance P receptors in pancreatic acini.
AB  - In a previous study, we found that first incubating guinea pig pancreatic acini
      with carbachol caused desensitization of the enzyme secretory response to
      cholecystokinin-octapeptide (CCK-8), bombesin, and carbachol but not that to
      substance P. This carbachol-induced desensitization could be accounted for by
      carbachol-induced down-regulation of receptors for CCK-8, bombesin, and
      carbachol. Although carbachol did not desensitize the enzyme secretory response
      to substance P, an effect of carbachol on substance P receptors was not examined.
      In the present study, in dispersed acini from guinea pig pancreas, substance P
      caused a twofold increase in amylase secretion. Stimulation was half-maximal at
      0.7 nM and was maximal at 10 nM. Analysis of the ability of substance P to
      inhibit binding of 125I-substance P to substance P receptors indicated that acini
      possess a single class of receptors for substance P (Kd = 0.8 +/- 0.1 nM; Bmax =
      1,037 +/- 145 fmol/mg of DNA). There was a close correlation between the relative
      potency with which substance P stimulated amylase secretion (0.7 nM) and the
      potency for inhibiting binding of 125I-substance P (Kd = 0.8 nM). First
      incubating pancreatic acini with carbachol did not alter either substance P
      stimulated enzyme secretion or binding of 125I-substance P to substance P
      receptors, whereas in the same experiments, carbachol reduced binding of 125I-CCK
      8 to cholecystokinin receptors by 50% and decreased in CCK-8-stimulated enzyme
      secretion by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379368
TI  - Differences in secretory granule content in pancreatic acinar cells from peri
      insular and tele-insular regions.
AB  - By applying morphometrical and quantitative double immunocytochemical techniques,
      differences in size and in amylase and chymotrypsinogen contents were found among
      pancreatic zymogen granules. These differences were present in granules of peri
      insular and tele-insular acinar cells, the peri-insular ones displaying higher
      numbers of granules of smaller sizes. No correlation was found among enzyme
      contents in individual granules, nor was there a correlation between enzyme
      content and granule size. The results suggest that each individual secretory
      granule is formed in an independent way and that each enzyme is processed and
      packaged into granules independently. The differences among granules may be
      associated with nonparallel secretion, since this phenomenon has been reported in
      the intracellular processing of secretory enzymes. This hypothesis, however,
      remains to be demonstrated.

PMID- 1379367
TI  - The effect of pretranslational regulation on synthesis of pancreatic colipase in
      streptozotocin-induced diabetes in rats.
AB  - A significant increase in synthesis of pancreatic colipase in streptozotocin
      (STZ)-induced diabetes in rats has been demonstrated previously. The aim of the
      present study was to identify whether this change in colipase synthesis was
      related to a pretranslational or translational regulation. The levels of
      colipase, lipase, and amylase mRNA were determined by Northern blot
      hybridization. The enzymatic activities and synthesis rates for these proteins
      were determined. One week after injection of STZ, the mRNA levels for both
      colipase and lipase were increased by about 100% over control, with accompanying
      increases in enzyme synthesis rates and enzymatic activities. The amylase mRNA,
      amylase synthesis rates, and amylase activity decreased by 95%. Insulin injection
      at a dose of 2 U/100 g/day for 5 days restored enzyme mRNA levels as well as
      enzyme activities. Kinetic studies revealed that lipase mRNA rapidly increased
      after induction of diabetes, closely followed by increases in lipase synthesis
      rates and lipase content. Colipase mRNA also rapidly increased, with values 60,
      85, and 82% over control 1, 2, and 3 days after STZ injection, respectively. But
      the colipase synthesis rate increased slowly, being only 10, 20, and 40% over
      control 1, 2, and 3 days after STZ treatment, respectively. Colipase content did
      not increase until 4 days after STZ injection (3 days after the increase in
      colipase mRNA). The decrease in amylase mRNA was paralleled by decreases in
      amylase synthesis rates and amylase content. In conclusion, the increase in
      colipase content in STZ-induced diabetes in rats is a consequence of enhanced
      transcriptional or pretranslational regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379369
TI  - Inactivation of the human immunodeficiency virus type 1 (HIV-1) by ultraviolet
      and X irradiation.
AB  - Here we report the kinetics of inactivation of HIV-1 by ultraviolet (UV) or X
      irradiation. Inactivation of HIV-1 by UV irradiation followed quasi first-order,
      i.e., single-hit, kinetics. The LD37 for inactivation of syncytia formation in
      SupT1 cells by limiting dilutions was approximately 780 J/m2. The LD37 for
      inactivation of HIV-1-induced syncytia by UV irradiation was nearly identical
      when measured in UV repair-proficient and -deficient lymphoblastoid cell lines
      (LCLs), demonstrating that immediate host cell reactivation (repair) of UV damage
      in the HIV-1 genome does not occur. The ability of HIV-1 to induce the
      accumulation of reverse transcriptase activity showed similar dose-dependent
      inhibition by UV irradiation (LD37, 845 J/m2). Inactivation of HIV-1-induced
      syncytia formation by X rays also approached first-order kinetics. The LD37 for
      syncytia formation as measured by limiting dilutions was approximately 3 x 10(3)
      Gy. HIV-1-induced accumulation of reverse transcriptase activity was slightly
      more resistant to inactivation by X rays, with an LD37 of approximately 4.5 x
      10(3) Gy. Syncytia-forming ability was still present in HIV-1 preparations X
      irradiated with 1.6 x 10(4) Gy. For the first time, we utilized the polymerase
      chain reaction (PCR) to measure the effects of radiation on virus replication. A
      decrease in the presence of the HIV-1 DNA could be detected by PCR in PBL
      cultures infected with UV- and X-irradiated virus. It required 12.96 J/m2 to
      eliminate the signal specific for HIV-1 DNA completely. The ability of HIV-1 to
      establish long-term infection in LCLs was also resistant to UV and X irradiation.
      Only linear and circular forms of HIV-1 DNA could be detected in LCLs established
      from PBL cultures infected with UV-irradiated virus. The significance of the
      relative resistance of HIV-1 to inactivation by UV and X irradiation is
      discussed.

PMID- 1379370
TI  - Disturbances in acute phase plasma proteins during melancholia: additional
      evidence for the presence of an inflammatory process during that illness.
AB  - 1. Leukocyte enumeration through flow cytometry has revealed that severe
      depression may be accompanied by a systemic immune activation, indicative of an
      inflammatory response. The latter condition allegedly involves an important
      modification of acute phase plasma protein (APP) equilibrium. 2. In order to
      elucidate whether the state of severe depression is represented by alterations in
      APPs, the authors measured: alpha 1 antitrypsin (alpha 1 AT), alpha 2
      macroglobulin (alpha 2 M), haptoglobin (Hp), alpha 1 acid glycoprotein (alpha 1
      S), transferrin (Tf), complement component 4 (C4) and C-reactive protein (CRP).
      Interleukin-1-beta (II-1 beta) and interleukin-6 (II-6) circulating levels were
      determined. 3. Hyperhaptoglobinemia and hypotransferrinemia are hallmarks for
      major depression and depression per se, respectively. The disorders in Hp and Tf
      circulating levels are highly sensitive to (83%) and specific for (100%)
      melancholia as opposed to the healthy state. 4. Disorders in both APPs are
      significantly related to the absolute number of blood monocytes. 5. The authors
      observed a trend towards lower alpha 2M and higher alpha 1S values in severely
      depressed subjects. Severity of depression was significantly related to Hp and
      alpha 1S (both positively) and to alpha 2M and Tf (both negatively) values. 6. No
      significant intercategory differences in C4 could be established, whilst only a
      few subjects exhibited measurable CRP, II-1 beta and II-6 circulating levels. 7.
      Our findings may support the hypothesis that depression is accompanied by an
      inflammatory response.

PMID- 1379371
TI  - Laser and photodynamic therapy of esophageal cancer.
AB  - With proper selection of patients with non-operative esophageal cancer,
      palliative therapy with Nd:YAG laser enhances the quality of life by improving
      the patient's ability to swallow soft or solid food. Also, the use of non-thermal
      laser light to initiate the process of photodynamic therapy (PDT) is an
      additional laser technique that appears effective, not just in palliative
      treatment, but also in the cure of early esophageal cancer. For PDT, considerable
      work will be necessary to provide standard techniques in tumor staging, light and
      drug delivery and in light dosimetry. Ultimately, palliative and curative therapy
      of esophageal cancer will most likely incorporate multiple modalities, including
      surgery, radiation, chemotherapy, stents, laser and other thermal modalities,
      photodynamic therapy, and combinations of these methods.

PMID- 1379372
TI  - Current role of laser and photodynamic therapy in gastrointestinal tumors and
      analysis of a 10-year experience.
AB  - Laser energy can be used for a variety of neoplastic diseases including benign
      tumors, early stage malignancies, and advanced carcinomas, either with curative
      intent or for palliation. Nd:YAG laser photocoagulation of 168 colorectal
      adenomas allowed a complete eradication in 70% of cases, after a mean follow-up
      of 22 months. Advanced and obstructing tumors were treated with Nd:YAG laser to
      recanalize the lumen. In the upper gastrointestinal tract the recanalization of
      the lumen by means of laser photocoagulation improved the quality of life and
      survival. In fact, in our series of 308 patients treated, 1-year survival was 23%
      in recanalized patients and 7% in nonrecanalized patients. In the lower
      gastrointestinal tract, 289 cancer patients were treated and an amelioration of
      symptoms related to the obstruction was obtained in 93%. The current indication
      for photodynamic therapy is mainly the treatment of flat or ulcerative early
      stage tumors in the esophagus and stomach of high risk patients. Out of 17
      patients treated, 14 were locally cured.

PMID- 1379373
TI  - Serum pre-S1 and pre-S2 antigens as prognostic markers in interferon therapy for
      chronic hepatitis B.
AB  - We investigated the changes of serum pre-S1 and pre-S2 antigens before and after
      interferon therapy in 35 carriers with HBeAg, to examine their clinical
      significance in the therapy. Both antigens were measured quantitatively by solid
      phase enzyme immunoassays using monoclonal antibodies specific to each antigen.
      The titers of these antigens of responders before therapy were significantly
      lower (p less than 0.001) than those of non-responders (6.23 +/- 1.09 versus 8.65
      +/- 2.09 and 4.46 +/- 1.27 versus 6.50 +/- 1.50, respectively). The titers
      decreased significantly 6 months after interferon therapy in the responders (p
      less than 0.05), whereas they did not change in the non-responders. Our findings
      indicate that pre-S1 and pre-S2 antigens have a close correlation with hepatitis
      B virus replication and are valuable markers for predicting the responsiveness to
      interferon therapy.

PMID- 1379374
TI  - Hydroxyurea induction of fetal hemoglobin synthesis in sickle-cell disease.
AB  - In the past 8 years, it has become apparent that some cytotoxic drugs that
      interfere with DNA replication can reprogram erythroid progenitors to switch from
      adult hemoglobin to fetal hemoglobin (HbF) production. Hydroxyurea has now been
      shown to substantially increase HbF in patients with sickle cell anemia. Since
      HbF interferes with sickle hemoglobin polymerization, hydroxyurea may become an
      important therapeutic agent for patients with sickle cell anemia.

PMID- 1379375
TI  - Spectrum of fetal hemoglobin responses in sickle cell patients treated with
      hydroxyurea: the National Institutes of Health experience.
AB  - Hydroxyurea is one of several cytostatic agents that increase fetal hemoglobin
      (HbF) production in some patients with sickle-cell disease, although their
      mechanisms of action remain to be defined. We have studied the effects of
      hydroxyurea in several hospitalized patients with sickle-cell disease treated for
      3 months, who were then maintained on outpatient therapy. Among hydroxyurea
      treated patients, we found that about 75% respond with at least a twofold
      increase in the percentages of F reticulocytes and HbF. Among the responders, HbF
      levels increased twofold to 10-fold, with three patients achieving levels of 10%
      to 15%. Statistical analysis of the three cellular variables that determine HbF
      levels in patients with sickle-cell disease--namely, increased F-cell production,
      F-cell survival, and HbF/F cells--disclosed that HbF production, as measured by
      an increase in F reticulocytes, accounted for about 70% of the HbF elevation,
      with smaller contributions coming from augmentation of HbF/F cells and
      preferential survival of F cells. Four responders were re-treated with their
      optimal weekly hydroxyurea dose, given either in daily fractions or over 4
      consecutive days, after a 1- to 3-month washout period. Greater HbF responses
      were attained with the optimal hydroxyurea dose than with the dose-regimen
      escalation, and usually occurred after a lag period. Furthermore, increases in
      HbF and F-cell levels were more rapid in patients receiving therapy on 4 out of 7
      days rather than on a daily schedule. Our calculations show that the increases in
      HbF/F and F cells and the decrease in the fraction of dense cells during limited
      hydroxyurea administration should cause a significant improvement in
      intracellular sickle hemoglobin polymerization tendency. Controlled prospective
      trials are necessary to establish whether these effects lead to clinical benefit.
      Alternate schedules of hydroxyurea administration, or its use in conjunction with
      other means to elevate HbF or reduce mean cell hemoglobin concentration, may
      achieve greater inhibition of polymerization and thus be more likely to result in
      unequivocal amelioration of disease manifestations.

PMID- 1379377
TI  - Provision of food and fluids in terminal care: a sociological analysis.
AB  - The artificial provision of nutrition and hydration to those with end-stage
      malignant disease is addressed. The physiology of cancer is investigated and is
      found to render such treatment futile in many instances. An analysis of the
      sociology of food, and the role of gender in its provision is discussed, and
      placed in the social milieu of the acute hospital, where there is to be found a
      cultural replication of the family. It is hypothesized that it is the synthesis
      of the powerful symbols of food and family that is at the root of behaviour in
      this area. Implications for patients and caregivers are explored.

PMID- 1379376
TI  - Hydroxyurea and erythropoietin therapy in sickle cell anemia.
AB  - Hydroxyurea has been shown to increase fetal hemoglobin (Hb F) production in
      patients with sickle cell disease and therefore has the potential to alleviate
      both the hemolytic and vaso-occlusive manifestations of the disease. Preliminary
      evidence indicates that recombinant human erythropoietin (rhEpo) may also induce
      Hb F. Three sickle cell anemia patients were treated with escalating doses of
      intravenous rhEpo and, subsequently, with daily oral hydroxyurea. After the
      optimal hydroxyurea dose was attained, rhEpo was added again. Two additional
      patients were treated with hydroxyurea alone. Treatment with rhEp, either alone
      or in combination with hydroxyurea, had no significant effect on the percentage
      of F reticulocytes or F cells. In contrast, hydroxyurea treatment was associated
      with a 1.5-fold to sevenfold increase in F cells and a 2.3- to 27-fold increase
      in the percentage of Hb F. In the three patients whose response reached a
      plateau, hydroxyurea treatment was associated with lessened hemolysis, decreased
      serum bilirubin and lactate dehydrogenase levels, and prolonged 51chromium
      labeled RBC survival. Hydroxyurea treatment also resulted in decreased numbers of
      irreversibly sickled cells and in decreased sickling at partial oxygen
      saturation, increased oxygen affinity, increased total RBC cation content, and
      diminished potassium:chloride co-transport. All five patients treated with
      hydroxyurea experienced a decrease in severity and frequency of painful sickle
      crises. This study confirms that hydroxyurea therapy increases Hb F production
      and provides objective evidence of a significant reduction in hemolytic rate and
      intracellular polymerization. In contrast, rhEpo, either alone or in combination
      with hydroxyurea, offered no measurable benefit. Based on these encouraging
      preliminary data, large-scale, controlled clinical trials are warranted to study
      the safety and efficacy of hydroxyurea in the treatment of sickle cell disease.

PMID- 1379378
TI  - [Whipple's disease. Radiologic and clinical wrong interpretation as non-Hodgkin's
      lymphoma].

PMID- 1379379
TI  - Galanin inhibition of enteric cholinergic neurotransmission: guanosine
      triphosphate-binding protein interactions with adenylate cyclase.
AB  - BACKGROUND: The ability of galanin, a unique 29 amino acid peptide, to affect
      cholinergic neurotransmission was examined in the guinea pig myenteric plexus.
      METHODS: The effects of galanin on tritiated acetylcholine ([3H]ACh) release were
      studied with cultured guinea pig myenteric plexus neurons. Functional
      correlations were made with longitudinal strips of ileal smooth muscle with
      attached myenteric plexus for examination of isometric contraction. RESULTS:
      Galanin abolished potassium-stimulated [3H]ACh release (170% +/- 18% of basal vs
      109% +/- 16%). Galanin inhibited [3H]ACh release stimulated by forskolin or
      cholera toxin. [3H]ACh release stimulated by cholecystokin octapeptide,
      calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide
      was also suppressed by galanin (10(-8) mol/L). Inhibitory effects were reversed
      by pertussis toxin preexposure, indicating involvement of guanosine triphosphate
      binding proteins. Galanin inhibited contractility of longitudinal smooth muscle
      strips exposed to cholecystokinin-8 (EC50 7.0 X 10(-9) mol/L for cholecystokinin
      alone vs 1.3 X 10(-8) mol/L for cholecystokinin-8 plus galanin) and abolished
      contractile responses to calcitonin gene-related peptide. CONCLUSIONS: Galanin
      inhibits cholinergic neurotransmission in myenteric plexus neurons. Inhibitory
      effects involve guanosine triphosphate-binding protein mediation.

PMID- 1379380
TI  - Heat-shock gene expression excludes hepatic acute-phase gene expression after
      resuscitation from hemorrhagic shock.
AB  - BACKGROUND: To determine whether the gene expression of both acute-phase
      reactants (APR) and the major heat-shock protein (hsp-72) can occur
      simultaneously, transcriptional rates were measured during shock and
      resuscitation. METHODS: A nuclear runoff technique was applied to hepatic biopsy
      specimens obtained from pigs before shock, during 40% blood volume hemorrhagic
      shock (1 and 2 hours), and after resuscitation (4 and 6 hours). RESULTS: Shock
      induced transcription of hsp-72 was elevated elevenfold over sham operation at 2
      hours (p less than 0.02, Mann-Whitney rank test). Individually shocked animals
      did not transcribe both classes of stress genes but segregated into two groups:
      (1) strong APR transcriptional responders and (2) hsp-72 transcriptional
      responders. In group 2, APR transcription was significantly suppressed.
      Antichymotrypsin transcription was an average of eighteenfold lower in group 2
      versus group 1 (p less than 0.05 at 1,2, and 6 hours). CONCLUSIONS: Different
      classes of stress protein genes are not transcribed simultaneously. We infer that
      their increased accumulation at the mRNA level is the result of sequential
      transcription. Hsp-72 transcription excludes that of the APR genes that may be
      critical to survival after stress.

PMID- 1379382
TI  - Influence of hypercortisolemia on the acute-phase protein response to endotoxin
      in humans.
AB  - BACKGROUND: The response to systemic infection includes the coordinated
      appearance of hepatic acute-phase proteins, the production of which may be
      influenced by a counterregulatory hormonal background. This study sought to
      assess the potential for hypercortisolemic conditions to influence fibrinogen
      kinetics and other acute-phase protein responses in humans with endotoxemia.
      METHODS: Eleven hospitalized healthy male volunteers underwent two separate
      determinations of fibrinogen kinetics, one baseline and one after administration
      of endotoxin (2 ng/kg intravenously; lot EC-5). Seven volunteers were studied
      without hormonal manipulation and four in the presence of a hypercortisolemic
      background (hydrocortisone infusion, 3 micrograms/kg/min). Fibrinogen fractional
      synthetic rates were estimated from the incorporation of orally administered 15N
      glycine, and fibrinogen, C-reactive protein, cortisol, tumor necrosis factor
      alpha, and interleukin-6 levels were also determined. RESULTS: The presence of an
      antecedent hypercortisolemic background resulted in an attenuated interleukin-6
      response, as well as decreased fibrinogen synthesis and C-reactive protein
      appearance. CONCLUSIONS: The current data suggest that glucocorticoid hormonal
      influences are of importance in the regulation of endotoxin-induced cytokine and
      acute-phase protein responses.

PMID- 1379381
TI  - Protein kinase C is a mediator of the adaptation of vascular endothelial cells to
      cyclic strain in vitro.
AB  - BACKGROUND: The mechanism by which hemodynamic forces influence the function of
      the endothelium lining a blood vessel are unknown. The aim of this study was to
      determine the effect of in vitro cyclic strain on endothelial cell (EC)
      activation of protein kinase C (PKC). METHODS: Confluent bovine aortic ECs grown
      on flexible-bottomed culture plates were subjected to 24% maximum strain at a
      frequency of 60 cycles/min for 24 hours. Changes in PKC activity and evidence of
      translocation from cytosol to membrane fractions were assessed by
      immunocytochemical staining of ECs with antibodies specific to PKC and direct
      measurement of PKC activity in cytosol and membrane. To determine whether
      activation of PKC was responsible for some effects of cyclic stretch on ECs, a
      specific PKC inhibitor, calphostin C, was added to ECs subjected to cyclic
      stretch for 5 days and control ECs grown under static conditions. RESULTS:
      Immunocytochemical staining of ECs demonstrated translocation of PKC alpha- and
      beta-antibody fluorescence from the cytosol to the perinuclear and nuclear
      regions in ECs subjected to cyclic strain. This was confirmed by direct
      measurements of PKC activity, which demonstrated an early transient translocation
      of PKC activity from cytosol to membrane fraction at 10 seconds followed by a
      sustained elevation in PKC activity in the membrane at 100 seconds. Calphostin C
      abrogated the increase in EC proliferation that occurs in response to stretch.
      CONCLUSIONS: We conclude that cyclic stretch of ECs results in activation of PKC,
      which may be responsible for mediating the effects of cyclic stretch on EC
      growth.

PMID- 1379383
TI  - [Postoperative--changed care to pain-free patients].

PMID- 1379384
TI  - Parenteral anticoagulation with the heparinoid Lomoparan (Org 10172) in patients
      with heparin induced thrombocytopenia and thrombosis.
AB  - Progressive thrombocytopenia may develop in as many as 5% of patients receiving
      heparin anticoagulation. In these patients, the risk of thromboembolic
      complications as well as continued thrombocytopenia necessitates discontinuation
      of heparin and initiation of an alternative anticoagulant when indicated. The
      heparinoid Lomoparan (Org 10172) is a mixture of several non-heparin low
      molecular weight glycosaminoglycans with proven anticoagulant efficacy that is
      generally non-reactive with platelets in the presence of plasma from patients
      with heparin induced thrombocytopenia, whereas standard heparin will induce
      platelet aggregation. We evaluated the role of heparinoid as a potential
      alternative anticoagulant in patients with heparin induced thrombocytopenia.
      During a 6 month period, we identified six patients with heparin induced
      thrombocytopenia who required an alternative parenteral anticoagulant, four as
      primary treatment for specific medical problem, and two as anticoagulation during
      a necessary surgical procedure. Heparinoid was used successfully in both medical
      and surgical patients requiring parenteral anticoagulation. In no case was there
      an exacerbation of the thrombocytopenia nor thromboembolic complications while on
      heparinoid therapy. Three of our patients sustained hemorrhagic complications,
      predominantly in the post-surgical setting in association with elevated anti
      factor Xa levels and additional anticoagulant agents. We feel that these results
      confirm the utility of heparinoid anticoagulation in a select subset of patients
      with heparin induced thrombocytopenia who require continued parenteral
      anticoagulation.

PMID- 1379385
TI  - Availability of the B beta(15-21) epitope on cross-linked human fibrin and its
      plasmic degradation products.
AB  - The binding of radiolabeled monoclonal antifibrin antibody 59D8 (specific for
      fibrin but not fibrinogen) to a series of degraded fibrin clots showed that the
      availability of the B beta(15-21) epitope (against which 59D8 had been raised)
      was inversely proportional to the extent of clot lysis. Examination of digest
      supernatants revealed that the B beta(15-21) epitope was released from clots as a
      high molecular weight degradation product in the presence of calcium ions but
      that the generation of low molecular weight peptides occurred in the absence of
      calcium ions. To address the question of epitope accessibility, we compared
      levels of fibrin clot binding among four radioactively labeled antibodies:
      antifibrin monoclonal antibody 59D8, two antifibrinogen monoclonal antibodies
      that cross-reacted with fibrin, and an affinity-purified polyclonal
      antifibrinogen antibody. We expected that the antifibrinogen antibodies would
      show enhanced binding to clots in comparison with the antifibrin antibody.
      However, the epitope accessibility experiments showed that all four antibody
      preparations bound fibrin clots at comparable levels. Taken together, these
      studies demonstrated that one fibrin-specific epitope, B beta(15-21), remains
      available on clots as they undergo degradation by plasmin and, importantly, that
      the epitope is not solubilized at a rate faster than the rate at which the clot
      is itself solubilized. The availability of the B beta(15-21) epitope during the
      course of plasminolysis assures the potential utility of antifibrin antibodies
      such as 59D8 for detecting thrombi and targeting plasminogen activators.

PMID- 1379386
TI  - Detection of Naka antigen and GP IV (CD36) mRNA in monocytes of Naka-negative
      subjects.

PMID- 1379387
TI  - The metabolism of cyclamate to cyclohexylamine and its cardiovascular
      consequences in human volunteers.
AB  - A group of 194 diabetic patients were given calcium cyclamate (1 g/day as
      cyclamic acid equivalents) for a period of 7 days. Blood and urine samples were
      collected to determine the formation of cyclohexylamine, which is an indirectly
      acting sympathomimetic amine. Blood pressure and heart rate were recorded before
      and after treatment. Urine samples were collected each day and analyzed for
      cyclamate (to check compliance) and cyclohexylamine (to monitor the development
      of metabolizing activity). After 7 days intake most individuals (78%) did not
      excrete significant amounts of cyclohexylamine (less than 0.1% of the daily dose
      of cyclamate) but a small number (8; 4% of the group) excreted more than 20% of
      the daily dose as cyclohexylamine in the urine. Similar interindividual
      variations were found in the plasma concentrations of cyclohexylamine after 7
      days intake of cyclamate, with 8 individuals having concentrations of 300-1942
      ng/ml. The changes in cardiovascular parameters in these 8 subjects between pre-
      and postdosing were similar to those found in 150 subjects with plasma
      cyclohexylamine concentrations less than 10 ng/ml. Twenty of the subjects were
      restudied after receiving calcium cyclamate for 2 weeks at a daily dose
      equivalent to 2 g of cyclamic acid (0.66 g tds). Plasma concentrations of
      cyclohexylamine, heart rate, and blood pressure were measured every 30 min for a
      period of 8 hr (one dose interval) after the final dose. Twelve patients had
      plasma concentrations of cyclohexylamine greater than 10 ng/ml (89-2043 ng/ml) at
      the start of the dose-interval investigations. There were no transient increases
      or decreases in plasma concentrations of cyclohexylamine which might have
      resulted in a transient change in blood pressure or heart rate. These data
      indicate that the metabolism of cyclamate (2 g/day) to cyclohexylamine would not
      affect blood pressure or heart rate even in individuals with high metabolizing
      ability.

PMID- 1379388
TI  - Repeated lindane exposure in the rat results in changes in spontaneous motor
      activity at 2 weeks post-exposure.
AB  - Male Wistar rats were given 25 doses of lindane, 10 mg/kg per day, 1 ml/kg p.o.
      in olive oil, or control vehicle. Two weeks after the last dose, the animals were
      assessed for modifications in spontaneous motor activity, plus-maze behavior,
      shuttle-box active avoidance acquisition, brain regional concentrations of
      biogenic amines and metabolites, and regional [35S]TBPS binding. Rats treated
      with lindane showed an increase in spontaneous motor activity. Although no
      additional behavioral or neurochemical modifications were found, the changes in
      activity observed at 2 weeks post-exposure further demonstrate the need to assess
      for long lasting neurobehavioral sequelae of repeated lindane exposure.

PMID- 1379390
TI  - [Catecholamine blood levels in sheep during superovulation in estrus].
AB  - The effects of a serum gonadotropin (SG) superovulation hormonal preparation were
      investigated on catecholamine levels (norepinephrine, dopamine and epinephrine)
      in the blood plasma of ewes with synchronized oestrus in the oestrus period. In
      this trial the blood plasma of eleven ewes of the Slovak Merino breed was
      analyzed to detect catecholamines in the oestrus period. Superovulation was
      induced by an i.m. administration of 1500 IU SG as soon as oestrus
      synchronization with Agelin vaginal tampons finished (20 mg chlorsuperlutin)
      which lasted for 10 days. Catecholamines were detected in the blood plasma before
      synchronization, on the day of Agelin vaginal tampons application, and in 48 and
      72 hours after the hormone administration--on the days of the expected ovulation.
      Catecholamine concentrations in the blood plasma were determined by a
      radioenzymatic assay using a Catechola test (Praha). The results indicate that
      synchronization and hormonal stimulation influence plasma catecholamine levels.
      The norepinephrine (NE) concentration in the blood plasma of the control samples
      has the value of 8.31 +/- 0.732 pmol/ml. An insignificant increase in the NE
      levels (13.12 +/- 0.120 pmol/ml; Fig. 1) was recorded on day 1 of the trial,
      after the start of synchronization. On the day of the expected ovulation the NE
      concentrations rose to 17.12 +/- 1.289 pmol/ml (P less than 0.001) and they
      remained significantly increased (P less than 0.01) at the level of 12.89 +/-
      1.020 pmol/ml on the following day of the experiment. The dopamine level (DA) in
      the plasma of a control sample is 6.42 +/- 0.350 pmol/ml (Fig. 2).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1379389
TI  - [Damage to human endothelial cells by cholestane-3 beta,5 alpha,6 beta-triol and
      the protective effects of preparations that raise the intracellular level of
      cAMP].
AB  - Effect of drugs, which are able to elevate the intracellular level of cAMP, on
      resistance of human umbilical vein endothelial cells (HUVEC) to cholestane-3
      beta,5 alpha, 6 beta-triol (Triol)-induced injury was studied. Triol at a
      concentration of 62 microM caused death of 50% of cells after a 24 hour
      incubation. Addition of forskolin (10 microM), methylisobutylxantine (100
      microM), or 8-Br-cAMP (100 microM) into the incubation medium prevented injury of
      HUVEC under these conditions. These findings indicate that endothelial resistance
      to the injury can be regulated by the adenylate cyclase system. A comparative
      study on Triol-induced injury of adult human aortic endothelial cells isolated
      separately from zones of low (LP) and high (HP) probability of atherosclerosis
      was also performed. In 7 cases endothelial cells isolated from the LP zones were
      more resistant to Triol-induced injury, in 2 cases the differences were not
      significant. The development of atherosclerotic lesion in HP zones is likely to
      be associated with a higher sensitivity of endothelial cells from these zones to
      different injuring agents.

PMID- 1379392
TI  - Definition of linear antigenic regions of the HPV16 L1 capsid protein using
      synthetic virion-like particles.
AB  - Mice of three haplotypes (H-2d, H-2b, and H-2d/b) were immunized with synthetic
      HPV16 virus-like particles (VLPs), produced using a vaccinia virus doubly
      recombinant for the L1 and L2 proteins of HPV16. The resultant anti-VLP antisera
      recognized HPV16 capsids by ELISA assay and baculovirus recombinant HPV16 L1 and
      L2 protein on immunoblot. Overlapping peptides corresponding to the HPV16 L1
      amino acid sequence were used to define the immunoreactive regions of the L1
      protein. The majority of the L1 peptides were reactive with IgG from the mice
      immunized with the synthetic HPV16 capsids. A computer algorithm predicted seven
      B epitopes in HPV16 L1, five of which lay within peptides strongly reactive with
      the murine antisera. The murine anti-VLP antisera failed to react with the two
      peptides recognized by anti-HPV16L1 monoclonal antibodies raised by others
      against recombinant L1 fusion protein. We conclude that the immunoreactive
      epitopes of HPV16 defined using virus-like particles differ significantly from
      those defined using recombinant HPV16 L1 fusion proteins, which implies that such
      fusion proteins may not be the antigens to look for HPV16L1 specific immune
      responses in HPV-infected patients.

PMID- 1379391
TI  - Localization of the virus neutralizing and hemagglutinin epitopes of E1
      glycoprotein of rubella virus.
AB  - Current serological assays using whole rubella virus (RV) as a target antigen for
      detecting RV-specific antibodies fail to define specific RV proteins and
      antigenic determinants such as hemagglutinin (HA) and virus-neutralizing (VN)
      epitopes of rubella virus. A panel of E1 deletion mutants and a subset of E1
      specific monoclonal antibodies (MAb) were used for the initial analysis of HA and
      VN epitopes of E1 glycoprotein. A peptide region (E1(193) to E1(269)) was found
      to contain HA and VN epitopes. Using both overlapping synthetic peptides and
      truncated fusion proteins within this region, the HA epitope defined by MAb 3D9F
      mapped to amino acid residues E1(214) to E1(240), while two VN epitopes defined
      by MAb 21B9H and MAb 16A10E mapped to amino acid residues E1(214) to E1(233) and
      E1(219) to E1(233), respectively. The epitopes defined in this study are
      recognized by antibody whether or not the epitopes are glycosylated.

PMID- 1379393
TI  - Epitope mapping and conformational analysis of SV40 T-antigen deletion mutants.
AB  - Deletion mutants of SV40 T-antigen were stably expressed in BALB/c 3T3E cells and
      characterized in immunoprecipitation assays using T-antigen-specific monoclonal
      antibodies. The epitope recognized by antibody PAb602 was narrowed to T-antigen
      residues 230-362. Coprecipitation results were compatible with a p53-binding
      region between T-antigen amino acids 347 and 517. Amino terminal deletions (1-108
      or 98-229) of T-antigen appeared to have pronounced effects on the conformation
      of distal regions of the molecule, based both on antibody binding and on
      association with p53.

PMID- 1379394
TI  - Enhanced sensitivity of a second generation ELISA for antibody to hepatitis C
      virus.
AB  - A second generation ELISA for combined detection of antibodies to three hepatitis
      C virus (HCV) recombinant proteins, i.e. C100, C33c and core, was compared with a
      first generation anti-HCV ELISA in which only antibodies to C100 are detected.
      The results of the ELISAs were evaluated in 225 haemophilia patients (panel A)
      and 44 patients with non-A, non-B (NANB) hepatitis (panel B). HCV infection was
      established by cDNA-polymerase chain reaction (PCR) (in panel B only) and by
      studying the anti-HCV reaction patterns in 4 separate ELISAs for detection of
      antibodies to the recombinant proteins C100, C33c, core and a combination of two
      synthetic peptides sp67/65 derived from the C100 region. The sensitivity for the
      detection of HCV infection had increased from 0.92[95% confidence interval (CI):
      0.87-0.95] to 1.00 (95% CI: 0.89-1.00) in haemophiliacs and from 0.84 (95% CI:
      0.66-0.95) to 1.00 (95% CI: 0.89-1.00) in NANB hepatitis patients when the second
      generation ELISA was used instead of the first generation ELISA. Concurrently the
      chance of a false negative result was reduced in panel A and B from 0.37 to 0 and
      from 0.28 to 0, respectively. Analysis of anti-HCV reaction patterns revealed
      that 172 of 206 (83.5%) anti-HCV ELISA-reactive haemophilia patients had
      antibodies to all 4 antigens tested. In the NANB hepatitis patients 18 of 31
      (58.1%) anti-HCV ELISA-reactive subjects reacted with 4 antigens. In the PCR
      tested panel of NANB hepatitis patients 2 subjects who showed antibody reactivity
      to only one antigen and 5 patients with reactivity to 2 antigens were PCR
      positive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379395
TI  - Antiglobulin testing for CR1-related (Knops/McCoy/Swain-Langley/York) blood group
      antigens: negative and weak reactions are caused by variable expression of CR1.
AB  - The Knops, McCoy, Swain-Langley and York antigens have recently been identified
      as being on complement receptor type 1 (CR1, CD35, C3b/C4b receptor). We examined
      the relationship between CR1 expression and the reactivity of the CR1-related
      blood group antigens with their specific antibodies. RBC from donors of selected
      phenotypes were tested by hemagglutination using two monoclonal antibodies to
      CR1, as well as anti-Kna, -McCa, -S1a, -'Kn/McC' and -Yka. Monoclonal antibodies
      3D9 and E11 required approximately 250 and approximately 400 CR1/RBC to obtain a
      positive reaction. Agglutination of antigen-positive cells by human polyclonal
      antisera was related to the CR1/RBC: thus, cells expressing 20-100 CR1/RBC were
      negative and included the previously designated null phenotypes for this
      collection, 100-150 were weak or negative, and greater than 200 were usually
      positive. One RBC sample carried Yka on the 190,000 dalton (A or F allele), but
      not the 220,000 dalton (B or S allele) variant of CR1, and gave inconsistent
      reactions with Yka antisera. These data provide an explanation for certain of the
      serologic characteristics of the CR1-related blood group antigen system.

PMID- 1379396
TI  - [Primary choriocarcinoma of the ovary--a case report].
AB  - A report is given on a rare case of nongestational primary chorionepithelioma of
      the ovary. A 30 years old woman was treated by salpingo-oophorectomy and
      methotrexate-monotherapy. She is showing long-term remission.

PMID- 1379397
TI  - Immunohistochemistry with keratin and smooth muscle actin monoclonal antibodies
      in canine digestive tract and extramural glands.
AB  - The canine digestive system and its extramural glands (parotid gland, liver,
      pancreas) were immunohistochemically studied using a panel of twelve monoclonal
      antibodies (MoAbs) specific for human keratin proteins and for alpha-smooth
      muscle actin. Various epithelial tissues and cells were characterized by
      different keratin staining patterns. So, the epithelial lining of the upper
      alimentary tract was characterized by staining with the MoAb 6B10, specific for
      keratin-type (K) 4, and the absence of staining with the MoAbs directed against K
      8 and 18 (CAM 5.2 and RGE 53, DE-K18 respectively), whereas the lower alimentary
      tract epithelium was not labeled by 6B10, but stained by the latter MoAbs. In the
      salivary glands the luminal and basal cells of the adenomeres as well as the
      different ductal structures could be immunohistochemically differentiated. The
      duct epithelium in liver and pancreas showed next to keratin staining
      characteristics in common with hepatocytes and exocrine pancreatic cells,
      additional staining by several keratin MoAbs. The keratin staining patterns in
      the canine tissues showed, in addition to similarities also distinct
      discrepancies when compared to the staining patterns in corresponding human
      tissues. Myoepithelial cells in salivary and oesophageal glands could be
      differentiated from other basally located epithelial cells by their exclusive
      immunoreactivity for alpha-smooth muscle actin. Canine pancreatic endocrine cells
      were not labeled by any of the keratin MoAbs. It is concluded that
      immunohistochemistry with polypeptide specific MoAbs specific for human keratin
      types can be used to differentiate between different types of canine epithelial
      tissues and epithelial cells in the digestive tract. As a result such reagents
      may find their application in developmental biology and pathology of this
      species.

PMID- 1379398
TI  - Foot-and-mouth disease virus C3 Resende subtype analysed by means of competition
      RIA using neutralizing monoclonal antibodies.
AB  - Foot-and-mouth disease virus (FMDV) was analysed using 30 monoclonal antibodies
      (MAbs) obtained from Balb/c mice immunized with FMDV C3 Resende (C3R) subtype 7
      and 14 days before fusion No. 15 and 16 respectively. Fourteen MAbs were
      neutralizing and by means of competition radioimmuno assay it was possible to
      classify them into four groups. The first group consisted of MAbs specific for
      three sequential and three conformational epitopes. The second group consisted of
      MAbs specific for two conformational and for one sequential epitope. The third
      and the fourth groups consisted only of one MAb each, being specific for
      conformationally and one sequentially dependent epitope, respectively.

PMID- 1379399
TI  - 2-Mercaptoethanol influences the in vitro function of bovine peripheral blood
      mononuclear cells.
AB  - The effects of 2-mercaptoethanol (2-ME) on some in vitro functions of bovine
      peripheral blood mononuclear cells (PBMC) were examined. It was shown that 2-ME
      enhanced, in a dose-dependent manner, the production of antibodies to bovine
      coronavirus. In this test the optimal concentration of 2-ME was 50 microM. This
      molarity of 2-ME was also optimal for the pokeweed mitogen (PWM)-induced
      proliferation of PBMC obtained from the 7 cattle tested. Similarly, the
      spontaneous proliferation of PBMC from 4 out of these cattle was enhanced. Thus,
      2-ME evoked an increase (up to 2.5 times) or a decrease (at most 10 times) of the
      quota between the PWM-induced and the spontaneous proliferation (stimulation
      index). In general, the presence of 50 microM 2-ME enhanced the in vitro
      production of interferon by bovine PBMC. On the contrary, the highest
      proliferative response of PBMC to stimulation with bovine virus diarrhoea virus
      was achieved in cultures without 2-ME or in cultures with 0.5 or 5 microM 2-ME.
      Since the effects of 2-ME varied, for different tests as well as for cattle
      tested, attention should be paid to the use of 2-ME in cultures of bovine PBMC.

PMID- 1379400
TI  - Discontinuous and continuous stimulation of FRTL-5 thyroid cells with bTSH cause
      different cAMP and nuclear proliferation antigen responses.
AB  - Pulsatile TSH secretion has been described in man. We investigated the effect of
      discontinuous TSH stimulation on FRTL-5 thyroid cells. FRTL-5 monolayers were
      pulsed with TSH in 4 h incubation periods with alternate 4 h TSH-free intervals,
      or continuously incubated with TSH. The cAMP production of cells was measured in
      the supernatant of monolayers. Expression of a nuclear proliferation antigen in
      FRTL-5 monolayers was determined by a monoclonal antibody (Ki-67) using the
      alkaline phosphatase-anti-alkaline-phosphatase staining method. The TSH
      concentration in the stimulation series ranged from 0.01 to 1.0 U/l medium.
      Rhythmic cAMP production was observed in both discontinuous and continuous
      stimulation. With discontinuous stimulation cAMP production peaked after about 24
      and 48 h, while in the continuous presence of TSH peaks were observed at 32-40
      and 48 h. At all TSH concentrations the effect of discontinuous stimulation was
      higher than in continuously stimulated cultures. The discontinuous incubation
      stimulated nuclear proliferation antigen expression of FRTL-5 more intensely and
      there was a positive correlation with TSH concentration. We conclude that the
      rhythmic pattern of cAMP production after TSH stimulation is independent of the
      TSH pulse. The amplitude of stimulation and proliferation of FRTL-5, however, is
      increased by discontinuous TSH application.

PMID- 1379401
TI  - Immunoreactive somatostatin in the rat ovary.
AB  - Immunoreactive SRIH was detected in the rat ovary (15.6 pg/mg wet weight, 520
      pg/mg protein) and was localized to the granulosa cells (168 +/- 6 pg/10(6)
      cells). Serial dilution studies showed parallelism of the inhibition curve for
      synthetic SRIH-14 and those of extracts of whole ovary and media conditioned by
      granulosa cells. The quantity of immunoreactive SRIH released into granulosa cell
      conditioned media decreased with time, while the intracellular content remained
      relatively constant. Gel chromatography showed peaks of immunoreactivity co
      eluting with SRIH-14 (38%), SRIH-28 (31%) and a high molecular weight component.
      The addition of synthetic SRIH-14 stimulated meiotic maturation in cumulus
      enclosed rat oocytes, with dose dependency being observed at SRIH-14
      concentrations between 1 and 1000 pmol/l. No evidence of pre-pro-SRIH gene
      expression could be demonstrated in either rat ovary or testis using both
      Northern analysis and reverse transcriptase/polymerase chain reaction
      amplification of polyadenylated RNA. SRIH may be produced in the ovary during a
      specific stage of ontogeny or by an alternative gene. It is also possible that
      SRIH is actively taken up and stored by granulosa cells without being produced
      locally.

PMID- 1379402
TI  - CD4+, CD33-, CD13-, CD14- acute monoblastic leukaemia.
AB  - We report a case of acute monoblastic leukaemia in which the expression of the
      CD4 antigen occurred in the absence of myeloid and monocytic lineage specific
      markers. Unexpected marker profiles have biological and diagnostic implications
      and we also suggest that the inappropriate expression of the CD4 antigen may be
      implicated in the poor prognosis of this case.

PMID- 1379403
TI  - Granulocyte colony-stimulating factor-producing malignant lymphoma.
AB  - A 71-year-old woman with leukocytosis was admitted for treatment of malignant
      lymphoma. During the clinical course, neutrophilia of unknown origin occurred in
      parallel with the progression of the malignant lymphoma. The supernatant of
      lymphoma tissue culture contained a high titer of granulocyte colony-stimulating
      factor (G-CSF), and lymphoma cells were positive when immunohistochemically
      stained by anti-G-CSF antibody. Western blot analysis and mouse colony assay of
      the supernatant also confirmed that the lymphoma produced G-CSF.

PMID- 1379405
TI  - Histochemistry of the human hair follicle with consideration of anagen phases I
      to VI.
AB  - The hair follicle is composed of different epithelial layers under participation
      of mesenchymal and nerval factors. The present study is an attempt to localize
      differentiation and functional markers in the human hair follicle during anagen
      phases I to VI. Monoclonal antibody K 8.12 against keratins 13 and 16 showed an
      increasing reactivity with certain types of the follicle epithelia during anagen
      I to VI. Ki67 was expressed within the innermost layer of the outer hair root
      sheath. Scattered Ki67-positive matrix cells could be additionally identified
      during anagen V and VI but were absent in anagen I to IV. During anagen Merkel
      cells became more abundant in the bulbar area. Neuropeptide-like immunoreactivity
      expressed by bulbar (especially matrix) cells were evenly seen during the early
      anagen I and II. The findings are in favour of a neurohumoral modulatory role
      during anagen phases accompanied by an increase of expression of certain
      proliferation-associated antigens like keratin 16 and Ki67 among the complex
      epithelia of human hair follicles.

PMID- 1379404
TI  - Hyaline-vascular type Castleman's disease with concomitant malignant B-cell
      lymphoma.
AB  - This case report describes a patient with localized hyaline-vascular (H-V) type
      Castleman's disease with concomitant malignant B-cell lymphoma. Malignant
      lymphoma has been described in association with multicentric type Castleman's
      disease, but not in association with the localized H-V type. Evidence for a
      relation between the two lesions in this patient by means of histologic, flow
      cytometric, cytogenetic and gene rearrangement studies was not found.

PMID- 1379406
TI  - Immunohistochemical evidence for the presence of oxytocin in the opossum corpus
      luteum.
AB  - Corpora lutea from opossums late in pregnancy were examined by
      immunohistochemistry for the presence of oxytocin. Oxytocin-immunoreactivity was
      observed in all corpora lutea examined but not elsewhere in ovarian tissue. The
      immunoreactive staining observed was confined primarily to the perinuclear
      cytoplasm of reactive luteal cells. Not all luteal cells showed oxytocin
      immunoreactivity. The immunohistochemical localization of oxytocin in the
      pregnant opossum corpus luteum demonstrates for the first time this peptide in a
      metatherian ovary. Its presence in this primitive species suggests that oxytocin
      has a fundamental role in the physiology of the mammalian ovary.

PMID- 1379407
TI  - Glycoconjugate composition of mammalian parotid glands elucidated in situ by
      lectins and glycosidases.
AB  - Sugar specific lectins (PNA, RCA I, LPA, SBA, DBA, GSA IB4, GSA II, WGA, LTA, UEA
      I, Con A, LCA) with and without prior selective glycosidase digestion (sialidase,
      alpha-fucosidase, alpha-mannosidase, beta-N-acetylglucosaminidase, alpha- and
      beta-galactosidase, beta-glucosidase) were used in order to investigate the
      distribution of native accessible carbohydrates and obtain information dealing
      with the composition of terminal disaccharides within glycoconjugates present in
      acinar compartments and ductal segments of mammalian (mouse, rat, hare, and
      rabbit) parotid glands. Glycoconjugates containing variable amounts of mannose,
      glucose, N-acetylgalactosamine and N-acetylglucosamine were present in the
      parotid glands of all species. However, these carbohydrate chains exhibited a
      different composition of terminal sequences within each type of gland. For
      example, sialylated components having the terminal dimers sialic acid-galactose
      and sialic acid-N-acetylgalactosamine were found in all acinar cells, whereas
      fucoglycoconjugates with terminal disaccharide fucose-galactose were localized in
      the rat striated ducts and hare acinar cells. The terminal sequence alpha
      galactose-beta-galactose was demonstrated in the mouse acinar cells. Finally,
      glycoconjugates characterized by the terminal dimer beta-galactose-N
      acetylgalactosamine were demonstrated in the mouse acinar and ductal cells and
      the rat ductal ones. Thus, present findings outlined and further confirmed the
      possibility to elucidate the oligosaccharide structure in situ using lectin
      histochemistry combined with enzymatic degradation.

PMID- 1379408
TI  - Histochemical analysis of sialomucin in Paget cells of mammary and extramammary
      Paget's disease.
AB  - The cytoplasmic sialomucin in Paget cells of both mammary and extramammary
      Paget's diseases was examined, using a new method proposed by Volz et al. (1987a,
      b). The staining methods used involved an electrolyte-Alcian Blue (pH = 5.8) and
      periodic acid Schiff. Oxidation was performed with 0.4 mmol/l periodate in 1
      mol/l HCl at 4 degrees C or 50 mmol/l periodate in distilled water at room
      temperature for 1 h. Methylation, saponification, borohydride reduction, and
      digestion with diastase, neuraminidase (Vibrio cholerae) or chondroitinase ABC,
      were also employed. The cytoplasmic mucin was found to exhibit positive reaction
      for the above staining which were variously altered by the chemical modification
      procedures and diminished in intensity or abolished by digestion with
      neuraminidase. These results suggest that the cytoplasmic mucin in Paget cells is
      sialomucin without side-chain substituent in genital Paget's disease, and that
      with a substituent at C7 in mammary Paget's disease.

PMID- 1379409
TI  - Peripheral neuropathy in monoclonal gammopathy of undetermined significance:
      prevalence and immunopathogenetic studies.
AB  - In an unselected series of patients with monoclonal gammopathy of undetermined
      significance (MGUS) we found neuropathy in 2 of 34 patients with IgG (6%), 2 of
      14 with IgA (14%), and 8 of 26 with IgM MGUS (31%). The neuropathy was
      subclinical in 6 patients (1 IgG, 1 IgA, and 4 IgM). Patients with IgG or IgA
      MGUS had a prominent motor impairment with electrophysiologic and morphologic
      findings suggestive of predominant axonal degeneration. No deposit of the M
      protein in sural nerve and no reactivity of the M-protein with nerve was detected
      in these patients. Patients with IgM MGUS had a prominent sensory impairment with
      evidence of predominant demyelination. In 6 of these patients the M-protein
      reacted with the myelin-associated glycoprotein (MAG). The higher prevalence of
      neuropathy in patients with IgM MGUS may be related to the frequent reactivity of
      IgM M-proteins with MAG.

PMID- 1379410
TI  - A study of right unilateral spatial neglect in left hemispheric lesions: the
      difference between right-handed and non-right-handed post-stroke patients.
AB  - We report 20 cases of right unilateral spatial neglect caused by lesions in the
      left cerebral hemisphere. Differences in neuropsychological symptoms and lesions
      sites are discussed in connection with handedness. Of the right-handed patients,
      6 had severe aphasia, 4 had Gerstmann's syndrome, and 1 had pure agraphia, but
      unilateral spatial neglect in these cases disappeared after a number of months.
      Six of the non-right-handed patients had moderate-to-severe aphasia, while the
      other 3 cases had no aphasia at all. Eight of the 9 cases in this group continued
      to have right unilateral spatial neglect for more than 6 months. Lesion site as
      determined by CT differed as to hemisphere, but all fell into the common area
      previously mentioned in connection with such disorders: i.e., the temporal,
      parietal and occipital lobes.

PMID- 1379411
TI  - Good drugs, bad drugs: helping kids know the difference.

PMID- 1379412
TI  - Prevalence of anti-HCV in cryptogenic cirrhosis in a suburban Detroit community.
AB  - To assess the role of the hepatitis C virus in patients with unexplained chronic
      liver disease, we tested for the presence of anti-hepatitis C antibody (anti-HCV)
      in the stored serum of patients with cryptogenic cirrhosis and a variety of other
      chronic liver diseases. The anti-HCV assay was performed by both the enzyme
      linked and recombinant immunoblot methods in 16 patients with cryptogenic
      cirrhosis. Eight of these 16 patients (50%) were seropositive. Six of these eight
      patients were born outside of the United States, compared with only one of eight
      seronegative patients (p = 0.021). Of the anti-HCV-positive cryptogenic cirrhotic
      patients, 50% also had markers of previous hepatitis B infection, compared with
      only 12.5% of seronegative patients. Evidence of anti-HCV positivity was found in
      10%, 19%, 0%, and 0% in patients with alcoholic cirrhosis, autoimmune hepatitis,
      primary biliary cirrhosis, and primary sclerosing cholangitis, respectively. We
      conclude that in a suburban American population, hepatitis C accounts for a
      significant percentage of patients with presumed cryptogenic cirrhosis.
      Unrecognized risk factors may account for a higher prevalence of HCV in foreign
      born patients with cryptogenic cirrhosis. A low prevalence of anti-HCV positivity
      is found in other forms of chronic liver disease.

PMID- 1379413
TI  - Cystic fibrosis patients bearing both the common missense mutation Gly----Asp at
      codon 551 and the delta F508 mutation are clinically indistinguishable from delta
      F508 homozygotes, except for decreased risk of meconium ileus.
AB  - The glycine-to-aspartic acid missense mutation at codon 551 (G551D), which is
      within the first nucleotide-binding fold of the cystic fibrosis transmembrane
      conductance regulator (CFTR), is the third most common cystic fibrosis (CF)
      mutation, with a worldwide frequency of 3.1% among CF chromosomes. Regions with a
      high frequency correspond to areas with large populations of Celtic descent. To
      determine whether G551D confers a different phenotype than does delta F508, the
      most common CF mutation, we studied 79 compound heterozygotes for G551D/delta
      F508, from nine centers in Europe and North America. Each subject was matched, by
      age and sex, with a delta F508 homozygote from the same center. A retrospective
      cohort analysis was performed on the following outcome parameters: age at
      diagnosis, sweat chloride, meconium ileus at birth, height, weight, weight for
      height, FVC, FEV1, chest X-ray score, pseudomonas colonization, pancreatic
      sufficiency, and Shwachman clinical score. There was less meconium ileus among
      the G551D/delta F508 compound heterozygotes (relative risk 0.33; 95% confidence
      interval .13-.86), as well as a trend toward later age at diagnosis of pancreatic
      insufficiency. No statistically significant difference was found between the
      groups for any other parameter. These results suggest that the CF genotype can be
      a predictor of pancreatic and intestinal phenotype. Prenatal counseling for the
      two genotype groups should differ only with respect to probability of meconium
      ileus. Clinical outcome (after survival of meconium ileus) for G551D/delta F508
      compound heterozygotes and delta F508 homozygotes is indistinguishable;
      therefore, prognostic counseling should not differ.

PMID- 1379414
TI  - Development, multiplexing, and application of ARMS tests for common mutations in
      the CFTR gene.
AB  - The amplification refractory mutation system (ARMS) is a simple, rapid and
      reliable method for the detection of any mutation involving single base changes
      or small deletions. We have applied ARMS methodology to the detection of
      mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
      Single ARMS tests have been developed for 11 CFTR mutations found in the
      northwest of England. ARMS reactions for the most common mutations have been
      multiplexed to give a test which will detect the presence of the delta F508,
      G551D, G542X, and 621 + 1G----T mutations in a DNA sample. The multiplex test has
      been validated by the analysis of over 500 previously genotyped samples and has
      been found to be completely accurate. The rapid detection of the most common
      mutations has enabled early molecular confirmation of suspected cystic fibrosis
      in neonates, rapid typing of cystic fibrosis patients and their relatives, and
      testing of sperm and egg donors.

PMID- 1379416
TI  - Surgical excision of subfoveal neovascular membranes in age-related macular
      degeneration.

PMID- 1379415
TI  - Mitochondrial tRNA(Thr) mutations and lethal infantile mitochondrial myopathy.

PMID- 1379417
TI  - Correlation between multi-headed spermatozoa in the ejaculate and histological
      findings in the testis.
AB  - Semen smears of 163 patients as well as bioptic material of 163 patients (93
      cases of paraffin histology and 70 cases of cryostat sections) were grouped by
      their content of multi-headed spermatozoa or multi-nucleated spermatids,
      respectively. It could be demonstrated that findings in the ejaculate concerning
      multi-headed spermatozoa are in good agreement with those in the testis in
      respect of the presence of double- and multi-nucleated spermatids. Furthermore,
      it could be shown that the frequency of multi-headed spermatozoa is positively
      correlated to inflammatory processes either of immunologic origin or caused by
      micro-organisms.

PMID- 1379418
TI  - Life-threatening anaphylactoid reactions to propofol (Diprivan)
AB  - Fourteen patients who had had a life-threatening reaction within a few minutes
      after receiving propofol (Diprivan) were investigated for anaphylaxis 4-6 weeks
      after the incident. Three kinds of immunologic tests were carried out: skin tests
      (prick tests and intradermal tests with the drugs used and Intralipid, the
      solvent for propofol), a leukocyte histamine release test, and a radioimmunoassay
      (RIA) of immunoglobulin E (IgE) against propofol and muscle relaxants, when they
      had been given with propofol. It had been previously shown that these were always
      negative in patients anesthetized with propofol without any complications.
      Thirteen of the 14 patients had at least one positive test supporting
      hypersensitivity to propofol; 2 patients had three tests positive; 4 had two
      tests positive; and 7 had one test positive. The skin tests with Intralipid were
      negative in 4 patients whose tests with propofol were positive. Two patients who
      had been given muscle relaxants at the same time as the propofol had positive IgE
      RIA to both drugs. In one patient, results of all the tests remained negative,
      and the mechanism involved in the reaction remained unidentified. It is note
      worthy that 9 patients of 14 had allergic histories that were known before the
      anesthetic (atopy; allergy to antibiotics, muscle relaxants, lidocaine, colloids)
      and that none of the patients had ever received propofol or Intralipid before. It
      is possible that the IgE that linked abnormally with the propofol had specific
      binding sites for the phenyl nucleus and the isopropyl groups, which are present
      in propofol and many other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379419
TI  - The role of radiotherapy in the primary management of cutaneous melanoma.
AB  - The historical role of radiotherapy in the management of cutaneous melanoma has
      largely been for palliation. Fractionation schedules using infrequent large doses
      have proved convenient and effective. Response rates range from 50% to 85% with
      the likelihood of complete response strongly dependent on tumor volume. These
      observations, along with radiobiological data showing a wide range of cellular
      radiosensitivity within the same histotype, suggest that radiotherapy would be
      most reliably effective against microscopic or subclinical disease. A few
      investigators have evaluated the role of radiotherapy combined with surgery as a
      curative approach in early-stage, high-risk disease. Patterns of failure after
      surgery alone indicate a substantial risk of local and regional recurrence that
      can be reduced by radiotherapy. Strategies for integrating radiotherapy into
      primary management are reviewed and additional studies are suggested.

PMID- 1379420
TI  - Dual Analyte immunoassay--a new approach to neural tube defect and Down's
      syndrome screening.
AB  - A microtiter plate based Dual Analyte enzyme-immunoassay method for the
      simultaneous measurement of alpha-fetoprotein (AFP) and Free-beta human chorionic
      gonadotrophin (hCG) was evaluated. This rapid assay, which has application in
      both Neural Tube Defect screening and Down's screening, shows good precision with
      between assay coefficients of variation between 5 and 7.5% for AFP and 3.7 to
      5.8% for Free-beta(hCG). Correlation with single analyte procedures is good, with
      correlation coefficients being greater than 0.91 in both cases. Clinical
      discrimination in detecting both types of abnormalities is not compromised by
      this new simultaneous Dual Analyte assay. We conclude that the Dual Analyte
      approach, which combines analytes achieving the highest known detection
      efficiency, will bring about improvements in the efficiency of screening, reduce
      costs and improve report turnaround, all leading to better quality of patient
      care.

PMID- 1379421
TI  - Urinary albumin and low molecular weight protein excretion in the nephrotic
      syndrome--sequential studies during corticosteroid treatment.
AB  - In a preliminary investigation into the behaviour of low molecular weight
      proteins in the nephrotic syndrome, we have measured urinary concentrations of
      albumin, alpha-1-microglobulin (alpha 1-m) and retinol-binding protein (RBP) in
      six children for up to 11 days during the course of steroid therapy for nephrotic
      syndrome. The results in part support the concept of independent proximal tubular
      absorption of albumin and low molecular weight proteins, and indicate that in the
      nephrotic syndrome the excretion of RBP and alpha 1-m, two generally accepted
      markers of tubular proteinuria, is anomalous.

PMID- 1379422
TI  - Ganglioside GD1b is the target antigen for a biclonal IgM in a case of sensory
      motor axonal polyneuropathy: involvement of N-acetylneuraminic acid in the
      epitope.
AB  - We report on a 54-year-old man with a sensory-motor polyneuropathy associated
      with a biclonal IgM-kappa gammopathy, which reacted with the ganglioside GD1b.
      Examination of nerve biopsy specimens showed some reduction in the density of
      myelinated fibers and axonal degeneration with a loss of large fibers and a
      relative increase in the density of small fibers. Immunodetection on thin-layer
      chromatography of the glycolipid antigens showed strong reactivity of the
      patient's serum IgM-kappa with GD1b ganglioside and weak binding to GD1a.
      biclonal IgM antibodies did not react with GM1, asialo-GM1, GT1b, GD2, or GD3.
      Indirect immunofluorescence staining showed binding of IgM-kappa mainly in a
      crescent-like pattern on the internal side of myelin sheaths, which could
      correspond either to an enlarged periaxonal (adaxonal) space or to the internal
      mesaxon or to both. The immunostaining was abolished after absorption of the
      serum with GD1b.

PMID- 1379423
TI  - Highly potent and selective inhibition of HIV-1 replication by 6-phenylthiouracil
      derivatives.

PMID- 1379424
TI  - Immunogenicity of free synthetic peptides corresponding to T helper epitopes of
      the influenza HA 1 subunit. Induction of virus cross reacting CD4+ T lymphocytes
      in mice.
AB  - Four linear synthetic peptides corresponding to residues 12-29, 50-67, 121-138
      and 131-147 of the HA 1 subunit of H3 subtype influenza virus (NT/60/68) were
      tested for their capacity to elicit in vivo peptide-specific CD4+ T cells cross
      reacting with whole virus. By studying the in vitro peptide proliferative
      response of lymph node cells from mice sensitized in vivo with free peptides
      emulsified in complete or incomplete Freund adjuvant, it was found that region 12
      29 could be recognized by CD4+ T lymphocytes in the context of H-2k and H-2b,
      region 50-67 in association with H-2b and region 121-138 in the context of H-2d
      MHC molecules. Outbred OF 1 mice could recognize regions 50-67 and 121-138.
      Peptides 50-67 and 121-138 are of potential interest for synthetic vaccine design
      since they induced in BALB/c (peptide 121-138) and OF 1 (both peptides) mice a
      CD4+ T cell population that cross reacted with whole virus. The region 50-67 is
      of particular interest since only few substitutions have been found in this area
      in natural variants of the H3 virus subtype.

PMID- 1379425
TI  - Epitope specificities of human serum antibodies reactive with respiratory
      syncytial virus fusion protein.
AB  - Respiratory syncytial (RS) virus continues to cause serious human respiratory
      disease and no prophylactic vaccine is yet available. Serum antibodies to RS
      virus fusion protein (F) that have the appropriate specificities and activities
      could confer protection against severe RS virus infections. To explore human
      serum antibody responses to RS virus F we first characterised four epitopes on F
      and then measured the concentrations of human serum antibodies to these sites for
      389 sera. Individuals varied in serum antibody concentration to the epitopes. The
      distribution patterns of the concentrations of antibodies reactive to each
      epitope were different. Antigenic variation of F at these epitopes in Southampton
      RS virus isolates was examined by immunofluorescence. The F proteins from
      different isolates varied within and between RS virus subtypes which co
      circulated in the outbreak of winter 1985-1986. Variations in F detected by
      immunofluorescence were consistent with differences between the strains'
      susceptibilities to monoclonal antibody antiviral action.

PMID- 1379426
TI  - Successful treatment of mycoplasmosis in layer chickens with single dose therapy.
AB  - The efficacy of treatment with single dose administration of 5 drugs at different
      dosages to layer hens naturally infected with Mycoplasma gallisepticum was
      studied. The drugs were tiamulin, which was administered orally, tylosin
      (parenterally and orally), spiramycin (orally), long-acting oxytetracycline
      (parenterally) and tylosindihydrostreptomycin (parenterally). Cure was assessed
      by the absence of nasal discharge. The cure rate was significantly higher (P less
      than 0.05) in treated hens than in untreated hens, as early as 1 day after
      treatment. Remission for 33 days was achieved in 60% of hens treated with 100 mg
      oxytetracycline, in 100% of hens treated with 100 mg or 200 mg spiramycin, in 92%
      and 85% of hens treated with 100 mg tylosin, parenterally and orally, and in 89%
      and 88% of birds given 100 mg tiamulin and tylosin-dihydrostreptomycin,
      respectively.

PMID- 1379427
TI  - Effect of albumin on adenylate cyclase receptor-related signal transduction of
      human peripheral blood mononuclear cells.
AB  - In the present study we investigated in vitro the effect of human serum albumin
      (HSA) on receptor-stimulated cAMP production in isolated human peripheral blood
      mononuclear cells (PBMC). The cAMP production is strongly correlated with the pH
      of the medium during long incubations with albumin. Adenylate cyclase is
      stimulated by receptor agonists like histamine, forskolin, prostaglandin E2 and
      the beta-adrenergic agonist isoprenaline, in the presence or absence of HSA. This
      protein, at concentrations above 0.1%, dose-dependently inhibits both basal and
      agonist-stimulated cAMP levels in PBMC. In the presence of 0.5% HSA a significant
      reduction of 30-60% (cell batch dependent) is induced, a reduction which is not
      incubation time dependent. Washing the cells after a period of incubation with 2%
      HSA does not reverse the HSA-induced cAMP inhibition. Oleic acid-evoked
      conformational changes in HSA were not capable of influencing the inhibition
      processes of HSA on the isoprenaline-stimulated cAMP production. Structure
      controlled interactions between HSA and membrane or adenylate cyclase are
      therefore unlikely. Bovine serum albumin and chicken albumin had different
      effects upon the agonist-stimulated cAMP production as compared with HSA. At this
      moment no explanation for this behavior can be provided. The findings indicate
      that albumin may inhibit non-specifically cAMP production in PBMC and possibly
      influences membrane-controlled processes.

PMID- 1379428
TI  - High percentage of CD8+, Leu-7+ cells in rheumatoid arthritis synovial fluid.
AB  - OBJECTIVE: While analyzing the phenotype of the synovial fluid mononuclear cells
      (SFMC) clustered about dendritic cells in rheumatoid arthritis (RA) joint
      effusions, it was noted that most of the clustering cells were CD8+ and
      coexpressed Leu-7. Therefore, the present study was conducted to investigate the
      frequency of CD8+, Leu-7+ cells in RA SF: METHODS: SFMC from 13 patients with RA
      and from 12 patients with non-RA inflammatory arthritides were examined for CD8
      and Leu-7 expression using 2-color immunofluorescence flow cytometry. RESULTS: RA
      SFMC had statistically significantly greater percentages of total CD8+ cells,
      total Leu-7+ cells, and CD8+, Leu-7+ cells, compared with SFMC from the non-RA
      patients. These RA CD8+, Leu-7+ SFMC had a distinctive electron microscopic
      appearance compared with CD8+, Leu-7- SFMC. When peripheral blood mononuclear
      cells (PBMC) from 31 RA patients (including 7 from the SFMC group) were compared
      with PBMC from 15 normal controls, the percentage of CD8+, Leu-7+ cells was not
      significantly greater in the RA patients. However, the combination of a modest
      increase in CD8+, Leu-7+ cells and a decrease in total CD8 cells in RA PBMC
      altered the composition of the RA CD8 population compared with normal PBMC, such
      that over 40% of RA peripheral blood CD8 cells coexpressed Leu-7. CONCLUSION: The
      increased frequency of CD8+, Leu-7+ cells in RA SFMC may arise from the fact that
      a high percentage of the CD8+ PBMC in RA patients are also Leu-7+. This altered
      composition of CD8 cells in RA SF may have a role in the pathogenesis of the
      disease.

PMID- 1379430
TI  - Immunopathology of rheumatoid arthritis. Antikeratin antibodies precede the
      clinical disease.
AB  - OBJECTIVE: We sought to determine whether circulating antikeratin antibodies
      (AKA) precede the onset of rheumatoid arthritis (RA). METHODS: By matching the
      registers of 2 previous population studies with the registry of patients
      receiving antirheumatic drugs several years later, pre-illness serum specimens
      could be obtained from 39 individuals who subsequently developed RA. AKA were
      assayed with the standard indirect immunofluorescence technique. RESULTS: Ten of
      39 serum specimens from individuals who subsequently developed seropositive RA,
      and 1 of 15 sera from individuals who developed seronegative RA, were positive
      for IgG-class AKA by immunofluorescence assay. The AKA-positive sera were also
      positive for rheumatoid factors. CONCLUSION: The findings focus attention on the
      role of pre-illness immunologic events in the pathogenesis of RA.

PMID- 1379429
TI  - Analysis of intraarticular fibrinolytic pathways in patients with inflammatory
      and noninflammatory joint diseases.
AB  - OBJECTIVE: Intraarticular activation of the fibrinolytic system has been
      suspected to occur in patients with arthritis. We undertook the present study to
      investigate the relation of this activation to clinical symptoms, and the
      molecular pathways involved. METHODS: We quantitatively assessed levels of
      plasmin-alpha 2-antiplasmin (PAP) complexes in synovial fluid (SF) from 25
      patients with rheumatoid arthritis (RA), 7 with seronegative spondylarthropathy
      (SSA), and 10 with osteoarthritis (OA), and conducted an analysis to determine
      the plasminogen-activating pathway via which these complexes were generated. In
      addition, we studied the relationship of intraarticular fibrinolysis to clinical
      and biochemical parameters. RESULTS: All patients studied had increased SF levels
      of PAP complexes. Levels in patients with RA and SSA were slightly higher than
      those in patients with OA. These complexes were probably formed by activation of
      urokinase-type plasminogen activator (u-PA), and not tissue-type plasminogen
      activator (t-PA), since SF levels of both u-PA antigen and u-PA-plasminogen
      activator inhibitor (PAI) complexes were increased in 27 of the 42 patients.
      Conversely, SF levels of t-PA were below normal in all but 1 patient. In some
      patients, activation of factor XII presumably also contributed to plasminogen
      activation in SF, since levels of factor XIIa-C1 inhibitor in SF were increased
      in 8 of the 42 patients and correlated, as did u-PA-PAI levels, with levels of
      PAP complexes. Several of the parameters of fibrinolysis in SF, particularly u-PA
      antigen and u-PA-PAI-1 complexes, were found to correlate with clinical and
      biochemical parameters. CONCLUSION: Our results suggest that plasminogen is
      frequently activated in the joints of patients with inflammatory or
      noninflammatory arthropathy and that this activation mainly occurs via a u-PA-,
      and in some cases also via a factor XII-, dependent pathway. The possible
      relation of this activation process to stimulation of synovial cells by cytokines
      is discussed.

PMID- 1379431
TI  - T cell receptor V beta repertoire of double-negative alpha/beta T cells in
      patients with systemic sclerosis.
AB  - OBJECTIVE: To analyze the T cell receptor V beta gene on double-negative (DN)
      alpha/beta T cells, which are increased in number, on peripheral blood
      lymphocytes (PBL) from patients with systemic sclerosis (SSc). METHODS: The DN
      alpha/beta T cells were sorted by flow cytometry from PBL obtained from 3
      patients with SSc. The V beta repertoire was analyzed by polymerase chain
      reaction. RESULTS: Only 1 or 2 V beta genes (V beta 5/7, 5, or 17) were
      predominantly expressed on DN alpha/beta T cells from these 3 patients.
      CONCLUSION: The V beta repertoire on DN alpha/beta T cells in PBL from patients
      with SSc is rather restricted.

PMID- 1379432
TI  - Autoantigenic epitopes of the B polypeptide of Sm small nuclear RNP particles.
      Identification of regions accessible only within the U1 small nuclear RNP.
AB  - OBJECTIVE: To analyze the autoantigenic epitopes of the Sm B polypeptide of the
      U1 small nuclear RNP (snRNP) using complementary DNA (cDNA) clones. METHODS:
      Expression of Sm B fusion proteins in lambda phage vectors, immunoblots,
      immunoprecipitations, and affinity purification of antibodies. RESULTS:
      Immunoblots using antibodies affinity-purified from B fusion proteins
      demonstrated that there were cross-reactive epitopes between the B'/B and A
      polypeptides of the U1 snRNP. Immunoprecipitation assays suggested that there
      were at least 3 different autoantigenic epitopes on the B polypeptide that could
      be classified into 2 general groups based upon autoantibody reactivity. The first
      group of autoantibodies, which bound 2 separate autoantigenic epitopes (BU1-1,
      BU1-2), participated in immunoprecipitation of the U1 snRNP alone. The second
      group, which bound the third type of autoantigenic epitope (BSm-1),
      immunoprecipitated all the abundant Sm snRNPs. CONCLUSION: There is at least 1
      region on the B proteins that is accessible to antibodies only within the
      structure of the U1 snRNP, as well as a region that is accessible on all Sm
      snRNPs. These data support the notion that the native U1 RNP, perhaps containing
      B proteins in a different conformation than those found on other Sm snRNPs, may
      drive the humoral immune response in systemic lupus erythematosus.

PMID- 1379433
TI  - Methemoglobinemia secondary to automobile exhaust fumes.
AB  - Methemoglobinemia is an uncommon cause of cyanosis. A 28-year-old male presented
      to the emergency department cyanotic and short of breath after exposure to
      noxious automobile fumes. He did not improve with the administration of 100%
      oxygen therapy. The initial arterial blood gas with cooximetry was: pH of 7.38,
      PaCO2 of 43 mm Hg, PaO2 of 118 mm Hg, measured oxygen saturation of 70%, and a
      methemoglobin level of 24.8%. Methylene blue was given (2 mg/kg intravenously)
      and the patient's symptoms resolved. On the following day he was discharged home
      without complication. A comprehensive review of the literature revealed no
      reported cases of methemoglobinemia secondary to accidental exposure to exhaust
      fumes.

PMID- 1379434
TI  - Nitric oxide: a pathogenetic factor in autoimmunity.
AB  - Nitric oxide (NO) has been identified recently as a multifunctional mediator,
      produced by, and acting on, most cells of the body. Besides its function as
      endothelium-derived relaxing factor, as a neurotransmitter and as an immune
      defence molecule, evidence is accumulating that NO participates in inflammatory-
      and autoimmune-mediated tissue destruction. Modulation of NO synthesis and action
      represents a new approach to the treatment of inflammatory and autoimmune
      conditions.

PMID- 1379435
TI  - Airway macrophages releasability in bronchial asthma.
AB  - Asthma is a multifactorial disease on genetic basis. Its development is
      influenced by maternal and environmental factors, i.e. allergens and adjuvants.
      Early identification of candidates at high risk for development of asthma will
      enable giving recommendations on preventive measures focussing on exposure to
      tobacco smoke and other pollutants, indoor and outdoor allergens and possibly
      viral infections during infancy.

PMID- 1379436
TI  - Function and specificity of human gamma/delta-positive T cells.
AB  - gamma/delta+ T-cells are a recently identified subpopulation of T-lymphocytes
      expressing an "alternative" T-cell receptor (TCR) molecule consisting of
      disulfate-linked or nonlinked gamma and delta chains. Despite a limited number of
      V gamma and V delta genes in the germ line, there is a large and diverse gamma
      delta TCR repertoire due to extensive N region variability. Recently developed
      monoclonal antibodies against V gamma and V delta gene products are useful
      reagents for the identification and isolation of gamma/delta+ T-cell
      subpopulations. The physiological significance of gamma/delta+ T-cells is still
      unknown. However, accumulating evidence indicates that human gamma/delta+ T-cells
      frequently recognize bacterial ligands as well as certain tumor cells.
      Interestingly, reactivity towards microbial antigens is usually restricted to a
      subpopulation of gamma/delta+ T-cells expressing a V gamma 9/V delta 2 TCR.
      However, different bacteria-reactive V gamma 9+/V delta 2+ gamma/delta+ T-cells
      display extensive N region variability, suggesting the involvement of a
      gamma/delta-specific superantigen in these responses. Little is known about the
      role of gamma/delta+ T-cells under pathological conditions. Rare cases of
      gamma/delta+ T-cell leukemias and lymphomas have been described. In addition,
      discrete changes in the distribution of gamma/delta+ T-cell subpopulations have
      been observed during HIV infection. Current thinking favors the interpretation
      that gamma/delta+ T-cells play a role in the immune reaction during infection and
      in the regulation of physiological or pathophysiological autoimmune responses.

PMID- 1379437
TI  - Structural analysis of class II major histocompatibility complex proteins.
AB  - Numerous studies have contributed much data that, taken together, provide
      considerable insight into the structural features of class II molecules. The
      putative peptide-binding region has been modeled from the crystal structure of
      the class I molecule HLA-A2. Mutational analyses and peptide-binding studies
      support this model. Direct structural studies have established features of the
      noncovalent association of the alpha and beta chains of class II molecules, and
      detergents and phospholipids have been shown to affect class II protein structure
      and/or peptide-binding capacity. Spectroscopic studies have revealed dynamic
      features of class II molecules in solution, and suggest differences in the
      overall structures of class I and II molecules that may reflect differences in
      function.

PMID- 1379438
TI  - A technique for demonstrating the nerve supply of whole larynges.
AB  - At present there is a large gap in our understanding of the exact distribution of
      sensory and motor nerves within the larynx. Gross dissection is only accurate for
      large-caliber nerves, whereas microscopic sections show only isolated examples of
      terminal branching. To fill this gap, we modified an old technique called
      Sihler's stain to process five whole canine larynges. The technique requires
      eight steps that take approximately 3 months. The result is an entire larynx in
      which muscle and cartilage are rendered translucent, while nerve is
      counterstained. Nerve branching can be continuously traced from the large-caliber
      nerves to the terminal branches. We found that the nerve patterns are
      surprisingly complex and contain frequent anastomotic networks. This technique is
      a powerful tool for studying certain neurolaryngological problems.

PMID- 1379439
TI  - Antigenic change in a human IgG4-specific CH3 epitope upon binding of a
      monoclonal antibody against a neighboring IgG4-specific epitope.
AB  - Two sets of monoclonal antibodies (mAbs) probably reacting with two different
      epitopes in the CH3 domain of the human IgG4 molecule were studied. We observed
      that the commercially available mAb HP 6011 inhibited the antigen binding of the
      three mutually inhibitable mAbs, 40-A2, 41-E8 and 43-F11 (40-series), made by us.
      However, the 40-series mAbs, including those with similar affinity such as mAb
      HP6011, were not able to inhibit mAb HP 6011. When the 40-series mAbs were
      preincubated with IgG4, the mAb HP 6011 could partially displace these
      antibodies. This one-way inhibition indicates that upon binding mAb HP 6011
      changes the antigenic structure of the IgG4 molecule by disrupting the epitope
      for the 40-series mAbs. A steric hindrance of this epitope by mAb HP 6011 is more
      unlikely, since the small Fab fragment of mAb HP 6011 also inhibited the reaction
      of the 40-series mAbs.

PMID- 1379440
TI  - Squamous cell metaplasia of the bladder urothelium. A retrospective study of 36
      patients.
AB  - In a retrospective study of 28 women and eight men with squamous cell metaplasia
      in different parts of the bladder, including the trigone, no histopathological
      differences were observed among the regions. All the five (female) patients with
      parakeratosis had a concomitant invasive bladder tumour. Thirty-eight% of all the
      patients had a simultaneous neoplastic tumour. The metaplastic lesions were
      investigated for keratin in 13 patients, and all were positive. In seven out of
      eight patients, the urothelium adjacent to the squamous cell metaplasia was also
      positive for keratin, indicating a direct transformation of the urothelium to
      squamous cell epithelium. The metaplastic cells were investigated for oestrogen
      receptors in five men and five women, and all were negative, suggesting no
      relationship between estrogens and squamous cell metaplasia of the bladder.
      Squamous cell metaplasia in the bladder is not considered a premalignant
      condition. However, metaplasia and neoplastic tumours are often associated with
      chronic tissue damage, and the presence of metaplasia may give a warning of
      conditions that can also cause cancer.

PMID- 1379441
TI  - Using a cationic carbocyanine dye to assess RNA loading in Northern gel analysis.
AB  - In Northern blotting, one must have a means of assessing the uniformity of RNA
      loaded into each lane of a gel. As an alternative to "common gene" controls and
      previously published nucleic acid dyes (ethidium bromide, acridine orange,
      methylene blue), we have utilized a cationic carbocyanine dye (Stains All) for
      the assessment of RNA gel loading uniformity over the range of 5-25 micrograms
      RNA/lane. The following protocol is suitable for messages of well-characterized
      mobility and utilizes xylene cyanol as a 4-kb marker; as such, it will migrate
      between 28S and 18S rRNA over a wide range of agarose concentrations. Optimally,
      it is best that the message(s) of interest should migrate either as a smaller
      species than 18S or as a larger species than 28S; this allows either the 28S or
      18S ribosomal band to be separated from the message(s) of interest by severing
      the gel transversely at the xylene cyanol front. Severing the gel in such a
      manner makes it possible to simultaneously submit that portion of the gel
      containing either the 28S or 18S rRNA band to Stains All staining while
      immediately continuing with the transfer of that portion of the gel containing
      the mRNA of interest. We have found the dye to interact linearly with rRNA
      whether data were gathered by densitometrically scanning the gels themselves or
      photographs of the gels.

PMID- 1379442
TI  - PCR-generated probes for the study of DNA-protein interactions.

PMID- 1379443
TI  - CD59: a molecule involved in antigen presentation as well as downregulation of
      membrane attack complex.
AB  - CD59 is a recently discovered complement (C) regulatory protein. Three activities
      of CD59 have been recognized so far. It can downregulate the activation of the C
      cascade at membrane attack complex formation stage, it participates in T-cell
      rosette formation with erythrocytes and appears to be necessary for T-cell
      activation. CD59 is broadly distributed on cells of various organs and this is
      compatible with its function of protecting cells and tissues from incidentally
      activated autologous C. CD59 is encoded by a single gene residing on chromosome
      11. The entire sequence of CD59 cDNA is known, from which the amino acid
      structure of CD59 has been deduced. Mature CD59 is made up of 103 amino acids. It
      has two potential N-glycosylation sites. Carbohydrate constitutes about 20% of
      the molecular mass of CD59. The protein part of the molecule is covalently linked
      to an oligosaccharide which, in turn, is glycosydically linked to
      phosphatidylinositol (PI). CD59 is anchored to the cells via PI moiety. The fine
      structure of the PI anchor of CD59 has not yet been established. Decreased
      expression of CD59 has been shown in two diseases. In paroxysmal nocturnal
      hemoglobinuria, erythrocytes (type III) lacking CD59 (and other PI proteins) have
      susceptibility to lysis by membrane attack complex. In psoriasis, expression of
      CD59 (and CD55) is drastically decreased in psoriatic lesions, presumably due to
      PI cleavage involving signal transduction mechanism(s) leading to increased
      proliferation of various cell types in lesional skin.

PMID- 1379445
TI  - Selenium 1992. Proceedings of the International Symposium on Selenium. Belgrade,
      Yugoslavia, May 12-15, 1991. Papers and abstracts.

PMID- 1379444
TI  - Comparative aspects of basal forebrain organization in vertebrates.
AB  - The present survey shows that basal ganglia organization in the three classes of
      amniotes has many features in common. Yet, there are several differences that are
      important to note since they contribute to a better understanding of the
      evolution of those brain structures. They also underscore once again that it is
      questionable to generalize the results obtained in a certain species. This
      question is the more important in view of the general practice in mammalian
      research. Comparative studies may be of great help to solve this problem. The
      reported differences in acetylcholine release after pharmacological treatment in
      the striatum of rats and reptiles have stimulated further research that has led
      to the conclusion that the nucleus accumbens in the rat is a very heterogeneous
      structure with respect to the regulation of the release of acetylcholine by D2
      dopamine and NMDA receptor activation. In this regard, the striatum of reptiles
      may offer a model for studying the functioning of the caudomedial part of the rat
      nucleus accumbens.

PMID- 1379447
TI  - Effects of glutathione and of cysteine on intestinal absorption of selenium from
      selenite.
AB  - The influence of glutathione (1 mmol/L) (GSH) on in vitro mucosal uptake and in
      vivo absorption of 75Se-labeled selenite (10 mumol/L) was investigated in rat
      jejunum. For comparison, the effect of L-cysteine (1 mmol/L) on in vivo
      absorption of 75Se-labeled selenite was also studied. In the in vitro uptake
      experiments, only the mucosal surface was exposed to the incubation medium for 3
      min. For the in vivo experiments, a luminal perfusion technique was employed. GSH
      inhibited in vitro mucosal Se uptake, whereas absorption in vivo was stimulated
      by GSH. L-Cysteine also stimulated in vivo Se absorption, confirming former in
      vitro mucosal uptake experiments. Thus, unlike L-cysteine, GSH affected in vitro
      and in vivo absorption of Se from selenite differently. Enzymatic cleavage of
      products of the reaction of selenite with GSH occurring more efficiently under in
      vivo than in vitro conditions may be a prerequisite for the stimulatory effect of
      GSH on Se absorption. This apparently does not apply to the stimulatory effect of
      cysteine. Since GSH occurs in the intestinal lumen under physiological
      conditions, it may contribute to the high bioavailability of Se from selenite.

PMID- 1379446
TI  - Etiologic factors and pathologic alterations in selenium-vitamin E deficiency and
      excess in animals and humans.
AB  - The etiology of selenium-vitamin E (Se-E) deficiency diseases may be complex.
      Many of the syndromes involve combined deficiency of selenium and vitamin E.
      Selenium moves into the animal and human food chain from soil and plants, which
      may contain inadequate amounts of the nutrient in many areas of the world.
      Vitamin E may be in low concentration in many animal feeds unless supplements are
      added. Some syndromes, such as steatitis in cats, result from an increased
      requirement of vitamin E in diets that contain large amounts of polyunsaturated
      fatty acids, and these diseases will only respond to vitamin E administration.
      Deficiency syndromes in animals owing to pure Se deficiency are infrequent and
      have been produced mainly by laboratory studies utilizing extreme deficiency
      conditions. Other factors that may affect the occurrence of these deficiency
      diseases are concurrent dietary deficiency of S-containing amino acids,
      bioavailability of different forms of dietary Se, intake of compounds that
      antagonize Se (e.g., silver salts), and exposure to various prooxidant substances
      (e.g., iron compounds, oxygen, ozone, and various drugs).

PMID- 1379449
TI  - Glycoalkaloid and nitrate content of potatoes as affected by method of selenium
      application.
AB  - A comparison of two methods of selenium application, banding and foliar spray, of
      sodium selenite (Na2SeO3) on total glycoalkaloid (TGA) and nitrate nitrogen (NO3
      N) was studied during each of two consecutive years. The levels of application
      used were 0.0, 1.6 (0.75), 3.36 (1.5), and 5.6 (2.5) kg/ha (ppm soil). Both TGA
      and NO3-N were significantly reduced by application of 1.5 and 2.5 ppm of sodium
      selenite. Tuber selenium levels were significantly increased at all levels of
      application, using either banding or foliar spray, but were well below the toxic
      range for human consumption. Banding resulted in greater uptake of Se, and
      greater decreases in TGA and NO3-N as compared to foliar spray.

PMID- 1379451
TI  - Metabolic differences and similarities of selenium in blood and brain of the rat
      following the administration of different selenium compounds.
AB  - A common intermediate, i.e., selenite, was found in the serum of the rat; the
      maximum levels occurred 3 h after administration independent of chemical forms.
      This indicates that both the reduction of selenate to selenite, and oxidation of
      seleno-dl-methionine to selenite existed in the metabolic pathways of the rat. We
      found that water-soluble selenium compounds led to a similar maximum content in
      blood and serum, but seleno-dl-methionine had a higher affinity for the brain
      and, by gel filtration chromatography, for the higher mol-wt (25-100 K Da)
      fractions of serum protein, when compared with inorganic forms.

PMID- 1379450
TI  - Selenium and blood pressure studies in young and adult normotensive, renal, and
      spontaneously hypertensive animals.
AB  - With reports of either no change or reduction of blood pressure, the relationship
      between selenium and blood pressure has not been clear. Normal Se values are not
      available for the Sprague Dawley (SD) rat or in the young and adult rat with
      various models of experimental hypertension. This study measured serum Se levels
      in the young and adult normotensive (NT), Grollman renal hypertensive (RH), and
      Okamoto-Aoki spontaneous hypertensive rats (SHR). The young animals have
      statistically significant (P less than 0.001) lower Se values as measured by the
      fluorometric method than those found at adulthood. Selenium levels were found to
      be altered in the adult SHR animals when compared with the RH and NT animals. The
      serum Se value for the normotensive SD rat was found to be 65.0 +/- 3.5
      micrograms/dL, and for the two experimental models, 63.7 +/- 4.6 micrograms/dL
      for the RH, whereas the SHR level was elevated to 75.04 +/- 4.8 micrograms/dL (P
      less than 0.001). Elevated serum Se values in the adult SHR animals suggests an
      altered metabolism in SHR animals.

PMID- 1379448
TI  - Stimulation of mucosal uptake of selenium from selenite by some thiols at various
      sites of rat intestine.
AB  - The influence of several thiols (conc. 1 mmol/L) on mucosal uptake of 75Se from
      75Se-labeled selenite (conc. 10 mumol/L) across the brush border of rat jejunum
      and cecum was investigated in vitro using a short-term uptake technique. L
      Cysteine (L-Cys) stimulated 75Se uptake in the mid- and distal jejunum and cecum,
      but not in the proximal jejunum. The effect was maximal in the distal jejunum. D
      Cys was less effective in the jejunum and similarly effective in the cecum. L
      Leucine (L-Leu) and L-glutamic acid significantly reduced the stimulatory effect
      of L-Cys on Se uptake in the distal jejunum, whereas the respective effect of D
      Cys was not diminished by L-Leu. Cysteamine stimulated mucosal 75Se uptake at all
      intestinal sites tested, whereas the effect of mercaptopyruvate was restricted to
      the distal jejunum. Thioglycolate also enhanced 75Se uptake in the distal
      jejunum. The stimulatory effects of L-Cys, mercaptopyruvate, and thioglycolate
      were Na(+)-dependent, whereas the effect of cysteamine also occurred in the
      absence of Na+. Mercaptosuccinate, D-penicillamine, ergothioneine, and
      thiosulfate did not enhance mucosal 75Se uptake. It is concluded from these
      findings that the reaction of some thiols with selenite results in Se compounds
      that are rapidly absorbed by the intestinal epithelium through various Na(+)
      dependent and Na(+)-independent mechanisms. The high bioavailability of Se from
      selenite found by others might thus be the result of the presence of thiols in
      the gastrointestinal tract.

PMID- 1379452
TI  - Lymphocyte glutathione peroxidase activity during exacerbations in multiple
      sclerosis.
AB  - Glutathione peroxidase, one of the major antioxidants in the human brain, has
      been found to have decreased activity in patients suffering from multiple
      sclerosis (MS). This study compares the activity of lymphocyte glutathione
      peroxidase (L-GSH-px) in MS patients suffering from acute relapses with
      clinically stable MS patients and with control patients referred with
      nondemyelinating neurological diseases. All three groups showed an increase of
      mean enzymatic activity (MEA) during the observation period. The highest MEA in
      this study was observed in the MS groups. However, there were no significant
      differences in the L-GSH-px activity in the three groups. These results are not
      in accordance with previous investigations, and the need for further research in
      this field is emphasized.

PMID- 1379453
TI  - Some properties of selenoprotein P.
AB  - Selenoprotein P is a newly characterized selenoprotein. It is the first protein
      described to contain multiple selenocysteines. It is secreted by the liver into
      the plasma and turns over rapidly. Its concentration is sensitive to the selenium
      status of the animal. Its function is unknown.

PMID- 1379454
TI  - Biogeochemical regioning problems and the biogeochemical selenium provinces in
      the former USSR.
AB  - Current trends in biogeochemical research in the former USSR are exemplified for
      the trace element selenium (Se). Vast regions of the former USSR are low in Se,
      giving rise to selenium deficiency diseases in animals and to Kaschin-Beck
      disease in humans, whereas isolated high-Se regions are comparatively rare. The
      Se content of plants depends on geological soil-type and secondary processes such
      as weathering and leaching. In general, a direct correlation between the Se
      content of feedstock and of the blood in animals is observed, whereas
      corresponding data for humans remain to be accumulated.

PMID- 1379455
TI  - Selenium deficiency in Yugoslavia.
AB  - Data on selenium (Se) deficiency in Yugoslavia are presented. The results include
      Se content of soil, cereal crops, and garlic grown in these soils, and human
      serum and scalp hair from several towns and regions. All data indicate a serious
      Se deficiency: soil (n = 140), the mean value of 200 +/- 69.6 micrograms/kg Se;
      wheat, (58) mean = 20.5 +/- 12.4 micrograms/kg; corn, (79) mean = 13.7 +/- 13.6
      micrograms/kg; and garlic, (66) mean = 13.7 +/- 17.1 micrograms/kg Se. Analyses
      of human tissue show a very low Se status of the Yugoslav population: serum, (n =
      875) mean = 50.0 +/- 18.0 micrograms/L and scalp hair, (388) mean = 94 +/- 16
      micrograms/kg Se. In some regions, Se contents of grain, garlic, and human serum
      and hair are approaching those in the low-Se belt in China. It is assumed that
      very low Se status of a human population could be a risk factor in the
      development of Balkan Endemic Nephropathy (BEN) and in a high incidence of
      urinary tract tumors (UTT) in endemic areas.

PMID- 1379456
TI  - Selenium content and distribution in rat tissues irradiated with gamma rays.
AB  - The effects of supplementation with selenous yeast and ionizing radiation on
      selenium (Se) content and distribution were evaluated in rat tissues (liver,
      kidney, spleen, heart, muscle, blood, front brain, hind brain, hypothalamus,
      pituitary, adrenal glands, testes, and hair). This study had 16 Se-supplemented
      (0.5 micrograms Se/d) and 16 placebo adult male Wistar rats. One half of the
      animals (eight Se-supplemented and eight placebos) were irradiated with a single
      dose of 4.2 Gy from a Co-60 source and sacrificed 7 d after irradiation along
      with nonirradiated animals and analyzed for Se content determination. The data
      obtained showed that selenous yeast supplementation increased Se levels in rat
      tissues (highest increases in hypothalamus, 161%; hind brain, 126%; spleen, 110%;
      and adrenal gland, 105%). Ionizing radiation induced significant changes in Se
      content and distribution (decrease in liver, blood, hair, femoral muscle, spleen,
      and hypothalamus; increase in kidney, testes, adrenal glands, and brain of
      placebo group). Supplementation with selenous yeast reduces changes in Se content
      and distribution after irradiation. It seems that the animal tissue
      susceptibility to oxidative damage may be correlated to their ability to retain
      Se in tissues.

PMID- 1379457
TI  - Regulation of cellular immune responses by selenium.
AB  - Selenium (Se) is an essential nutritional factor that affects the development and
      expression of cell-mediated immune responses directed toward malignant cells.
      These studies have shown that dietary (2 ppm for 8 wk) or in in vitro (1 x 10(
      7)M) supplementation with Se (as sodium selenite) results in a significant
      enhancement of the proliferative responses of spleen lymphocytes from C57Bl/6J
      mice in response to stimulation with mitogen or antigen. Se deficiency (0.02 ppm
      for 8 wk) had the opposite effect. The alterations in the ability of the cells to
      proliferate, which occurred in the absence of changes in the endogenous levels of
      interleukin-2 (Il2) or interleukin 1, were apparently related to the ability of
      Se to alter the kinetics of expression of high-affinity Il2 receptors on the
      surface of activated lymphocytes. This resulted in an enhanced or delayed clonal
      expansion of the cells, and in an increased or decreased frequency of cytotoxic
      cells within a given cell population. The changes in tumor cytotoxicity were
      paralleled by changes in the amounts of lymphotoxin produced by the activated
      cells. Dietary Se modulations had a comparable effect on macrophage-mediated
      tumor cytodestruction. The results also suggested that Se exerts its effect 8-24
      h after stimulation, and that it most likely affects processes in the cytoplasmic
      and/or nuclear compartments of activated lymphocytes.

PMID- 1379458
TI  - The role of selenium in thyroid hormone metabolism and effects of selenium
      deficiency on thyroid hormone and iodine metabolism.
AB  - Selenium deficiency impairs thyroid hormone metabolism by inhibiting the
      synthesis and activity of the iodothyronine deiodinases, which convert thyroxine
      (T4) to the more metabolically active 3,3'-5 triiodothyronine (T3). Hepatic type
      I iodothyronine deiodinase, identified in partially purified cell fractions using
      affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also
      labeled with 75Se by in vivo treatment of rats with 75Se-Na2SeO3. Thus, the type
      I iodothyronine 5'-deiodinase is a selenoenzyme. In rats, concurrent selenium and
      iodine deficiency produces greater increases in thyroid weight and plasma
      thyrotrophin than iodine deficiency alone. These results indicate that a
      concurrent selenium deficiency could be a major determinant of the severity of
      iodine deficiency.

PMID- 1379459
TI  - A contribution to the world selenium map.
AB  - Atomic absorption spectrophotometric method was used to determine the serum
      selenium levels of 86 healthy individuals. Variations in age, sex, and
      geographically different urban regions of Yugoslavia were investigated. A group
      of 63 healthy children, ages 8-15 yr, were examined. Mean +/- standard deviation
      of the serum selenium concentration was 57 +/- 9 micrograms/L; age and geographic
      area had no effect on the Se status of children, but the difference between boys
      and girls was significant (P less than 0.05). A group of 23 men from Zagreb, ages
      22-37 yr, were examined. The group was divided into three age subgroups and no
      difference was found among these groups. The mean Se concentration was 69 +/- 18
      micrograms/L, and a statistically significant difference was found only between
      the group of adults and the group of children (P less than 0.05).

PMID- 1379461
TI  - Accidental selenium poisoning of growing pigs.
AB  - Chronic selenium (Se) toxicosis was diagnosed in two groups of growing pigs.
      Emaciation, loss of hair, necrotic areas in the skin, lesions of the coronary
      band and hooves, postnecrotic atrophic cirrhosis of liver, and lumbal
      poliomyelomalacia were the principal findings. High Se concentrations were
      detected in blood plasma. Addition of the calculated amounts of sodium selenite
      directly to the feedstuff instead to mineral premix was the cause of this
      intoxication.

PMID- 1379460
TI  - Selenium. Mechanistic aspects of anticarcinogenic action.
AB  - Selenium is increasingly recognized as a versatile anticarcinogenic agent. Its
      protective functions cannot be solely attributed to the action of glutathione
      peroxidase. Instead, selenium appears to operate by several mechanisms, depending
      on dosage and chemical form of selenium and the nature of the carcinogenic
      stress. In a major protective function, selenium is proposed to prevent the
      malignant transformation of cells by acting as a "redox switch" in the activation
      inactivation of cellular growth factors and other functional proteins through the
      catalysis of oxidation-reduction reactions of critical SH groups of SS bonds. The
      growth-modulatory effects of selenium are dependent on the levels of
      intracellular GSH and the oxygen supply. In general, growth inhibition is
      achieved by the Se-mediated stimulation of cellular respiration. Selenium appears
      to inhibit the replication of tumor viruses and the activation of oncogenes by
      similar mechanisms. However, it may also alter carcinogen metabolism and protect
      DNA against carcinogen-induced damage. In additional functions of relevance to
      its anticarcinogenic activity, selenium acts as an acceptor of biogenic methyl
      groups, and is involved in the detoxification of metals and of certain
      xenobiotics. In its interactions with transformed cells at higher concentrations,
      it may induce effects ranging from metabolic and phenotypical changes, and
      partial renormalization to selective cytotoxicity owing to reversible or
      irreversible inhibition of protein and DNA synthesis. Selenium also has
      immunopotentiating properties. It is required for optimal macrophage and NK cell
      function. Its protective effects are influenced by synergistic and antagonistic
      dietary and environmental factors. The latter include a variety of toxic heavy
      metals and xenobiotic compounds, but they are also influenced by essential
      elements, such as zinc. The exposure to antagonistic factors must be minimized
      for the full expression of its anticarcinogenic potential.

PMID- 1379462
TI  - Selenium status of patients with Balkan endemic nephropathy.
AB  - The selenium (Se) contents in common cereals in endemic and nonendemic areas in
      Serbia are very low. Plasma Se levels of both patients and healthy subjects, were
      also low, reflecting low Se intakes. Patients with Balkan endemic nephropathy
      (BEN) had significantly lower (p less than 0.05) plasma Se levels than healthy
      individuals, both from regions close to endemic areas, and from Belgrade. Mean
      plasma Se of BEN patients was slightly but insignificantly higher in samples
      taken immediately after dialysis than in those taken before, suggesting that very
      little of the Se present in plasma is dialyzable. Plasma SeGSH-Px activities
      before and after hemodialysis in both BEN and Nonendemic chronic renal failure
      (NCRF) patients were not significantly different, but BEN patients had lower
      enzyme activities than those with NCRF and healthy controls. In BEN patients, a
      significant correlation between plasma Se and SeGSH-Px activity was found.

PMID- 1379463
TI  - Modulation of the platelet thromboxane A2 and aortic prostacyclin synthesis by
      dietary selenium and vitamin E.
AB  - Vitamin E and selenium (Se) interact synergistically as an important antioxidant
      defense mechanisms. Se, an essential component of glutathione peroxidase (GSH-Px)
      and vitamin E decompose fatty acid hydroperoxides and hydrogen peroxides
      generated by free radical reactions. Vitamin E and GSH-Px may modulate
      arachidonic acid metabolism and the activity of cyclooxygenase enzymes by
      affecting peroxide concentration. The balance between arterial wall prostacyclin
      (PGI2) production and platelet thromboxane (TX)A2 directly influences platelet
      activity. In order to elucidate the differential role of dietary vitamin E and Se
      in aortic PGI2 and platelet TXA2 synthesis, 1-mo-old F344 rats were fed
      semipurified diets containing different levels of vitamin E (0, 30, 200 ppm) and
      Se (0, 0.1, 0.2 ppm) for 2 mo. Thromboxane B2 (TXB2) and 6-keto-PGF1 alpha, were
      measured by radioimmunoassay (RIA) after incubation of whole blood and aortic
      rings at 37 degrees C for 10 and 30 min, respectively. Vitamin E deficiency
      reduced plasma vitamin E to 5-17% of control-fed rats, and supplementation in
      vitamin E-supplemented animals increased plasma GSH-Px by 17%, compared to
      vitamin E-deficient rats. Se and vitamin E supplementation did not have a similar
      effect on TXB2 and PGI2 synthesis. Se deficiency did not alter platelet TXB2
      synthesis, but significantly decreased aortic PGI2 synthesis. It was necessary to
      supplement with both antioxidants in order to increase PGI2 synthesis. Se and
      vitamin E deficient groups had a higher TXB2/PGI2 ratio (0.17 +/- 0.08) compared
      to Se- and vitamin E-supplemented groups (0.03 +/- 0.01).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1379464
TI  - Serum selenium level in patients with colorectal cancer.
AB  - Serum selenium levels were determined by fluorometric procedure in 37 patients of
      both sexes suffering from colorectal cancer. The diagnosis was verified with
      histopathological examination during surgical treatment. The values found were
      46.8 +/- 11.2 micrograms/L. The control group consisted of 230 healthy persons
      from the same environment as the group of patients. The values found were 64.2 +/
      11.5 micrograms/L. The results of this study are compared with the results of
      the other research groups analyzing the level of selenium in colorectal cancer.

PMID- 1379466
TI  - Monitoring circulating B cells in patients with multiple myeloma at diagnosis or
      in plateau phase: how prevalent is light chain isotype suppression?
AB  - Peripheral blood lymphocytes from 25 patients with multiple myeloma at diagnosis
      or in plateau phase, and from 18 healthy subjects, were analysed for the surface
      expression of CD19 and immunoglobulin (Ig) light chain isotypes by dual parameter
      flow cytometry. The aim was to test for the existence of light chain isotype
      suppression (LCIS). LCIS is a hypothetical suppressor mechanism which supposedly
      operates in myeloma patients with stable disease, causing a drop in the number of
      circulating B cells bearing the same Ig light chain isotype as the myeloma
      paraprotein. Our experiments emphasized that the use of a non-Ig, pan-B cell
      marker, combined with dual antigen analysis, is necessary to distinguish Ig on B
      cells form (cytophilic) Ig on some non-B cells. We found good correlation between
      results obtained using polyclonal versus monoclonal anti-light chain antibodies,
      and washed blood versus peripheral blood mononuclear cells. There was no evidence
      of an abnormal ratio of CD19+, K+ to CD19+, lambda + cells in any of the
      patients. Thus, these patients did not manifest LCIS, and these experiments raise
      doubts about the existence of this phenomenon. The results also illustrate the
      problem that may arise in the interpretation of one parameter flow cytometry.

PMID- 1379465
TI  - Serum selenium and glutathione-peroxidase activities and their interaction with
      toxic metals in dialysis and renal transplantation patients.
AB  - Selenium, aluminum, cadmium, and magnesium concentrations and glutathione
      peroxidase activities in sera of 35 healthy individuals, 30 renal transplants,
      and 30 hemodialysis patients were measured. Serum selenium, aluminum, and cadmium
      concentrations in both groups of patients were higher than the controls (p less
      than 0.001), whereas the serum glutathione-peroxidase levels were lower (p less
      than 0.001). According to our results, it can be concluded that the patients
      receiving hemodialysis are subjected to more toxic elements than the
      transplantation patients. These findings imply that dietary selenium supplement
      may be suggested in renal failure for the detoxification of elements, such as
      cadmium and mercury. The essential trace element selenium takes part not only in
      the direct protection of endothelial cells against the accumulation of aggressive
      oxygen species, but also in the prevention of the toxic effects of cadmium or in
      the modulation of the active calcium transport.

PMID- 1379467
TI  - Effects of anti-TNF monoclonal antibody infusion in patients with hairy cell
      leukaemia.
AB  - Tumour necrosis factor (TNF) can act as an autocrine growth factor for hairy cell
      leukaemia (HCL) cells. The TNF produced by the malignant clone may also inhibit
      normal haematopoiesis thereby contributing to the cytopenias observed in patients
      with the disease. We have studied the effects of infusing a murine monoclonal
      anti-TNF antibody in three patients with HCL. In two patients receiving 0.5 mg of
      antibody/kg on alternate days for 12 d, the drug was well tolerated. The third
      patient received 2 mg/kg on alternate days and developed symptoms of serum
      sickness by day 9. In two patients with severe B-lymphocytopenia, circulating
      CD19 and CD20 positive, B-cells were restored to normal, the majority of which
      were negative for the HCL-associated marker CD11c. B-lymphocyte recovery was
      associated with a rise in serum immunoreactive IL-6 and with an early rise in
      immunoreactive TNF. These short courses of anti-TNF MAb treatment had modest
      effect on the tumour burden, producing a reduction in splenomegaly in one
      patient. Exploration of the effects of more prolonged administration of higher
      dose anti-TNF antibody will only be feasible when less immunogenic MAbs are
      available.

PMID- 1379468
TI  - Macrophage nitric oxide synthase: relationship between enzyme-bound
      tetrahydrobiopterin and synthase activity.
AB  - Nitric oxide synthase (NOS) (EC 1.14.23) catalyzes the oxidation of L-arginine to
      citrulline and nitric oxide. The complex reaction carried out by NOS, which
      involves NADPH, O2, and enzyme-bound FAD, FMN, and tetrahydrobiopterin (BH4), has
      only recently begun to be elucidated. Herein we report the characterization of
      the pterin requirement of murine macrophage NOS. Although purified NOS activity
      was not dependent on BH4, activity was significantly enhanced by BH4 in a
      concentration-dependent fashion. NOS purified in the absence of added BH4 was
      found to contain substoichiometric concentrations of enzyme-bound pterin, where
      increased concentrations of bound pterin correlated with an increase in activity
      when assayed in the absence of exogenous BH4. However, NOS purified in the
      presence of BH4 followed by gel filtration exhibited a 1 mol of pterin:1 mol of
      NOS 130-kDa subunit stoichiometry and activity that was essentially independent
      of exogenous BH4. Experiments to probe a redox role for the pterin were carried
      out using pterin analogues. 6(R,S)-Methyltetrahydropterin was found to increase
      NOS activity in enzyme purified in the absence of BH4. However, the deaza
      analogue, 6(R,S)-methyl-5-deazatetrahydropterin, was not only incapable of
      supporting enzymatic turnover but also inhibited citrulline formation in a
      concentration-dependent manner. Overall, these results support a role for BH4 in
      the NOS reaction that involves stabilization of the enzyme and redox chemistry
      wherein a 1:1 stoichiometry between bound pterin and NOS subunit results in
      maximum activity.

PMID- 1379469
TI  - A calcium and ATP sensitive nonselective cation channel in the antiluminal
      membrane of rat cerebral capillary endothelial cells.
AB  - The patch-clamp technique was applied to the antiluminal membrane of freshly
      isolated capillaries of rat brain (blood-brain barrier). With 1.3 mM Ca2+ in the
      bath, excision of membrane patches evoked ion channels, which could not be
      observed in cell-attached mode. The channel was about equally permeable to Na+
      and K+ ions, but not measurable permeable to Cl- and the divalent ions Ca2+ and
      Ba2+. The current-voltage curve was linear in the investigated voltage range (-80
      mV to +80 mV), and the single-channel conductance was 31 +/- 2 pS (n = 22). The
      channel open probability was not dependent on the applied potential. Lowering of
      Ca2+ to 1 microM or below on the cytosolic side inactivated the channels, whereas
      addition of cytosolic ATP (1 mM) inhibited channel activity completely and
      reversibly. The channel was blocked by the inhibitor of nonselective cation
      channels in rat exocrine pancreas 3',5-dichlorodiphenylamine-2-carboxylic acid
      (DCDPC, 10 microM) and by the antiinflammatory drugs flufenamic acid (greater
      than 10 microM) and tenidap (100 microM), as well as by gadolinium (10 microM).
      Thus, these nonselective cation channels have many properties in common with
      similar channels observed in fluid secreting epithelia. The channel could be
      involved in the transport of K+ ions from brain to blood side.

PMID- 1379470
TI  - High-affinity, equilibrative nucleoside transporter of pig kidney cell line (PK
      15).
AB  - Nucleoside transport was determined in the cloned porcine kidney cell line PK-15
      which exhibits properties of tubular cells. The cells did not express any Na(+)
      dependent, concentrative nucleoside transport. They exhibited only
      nitrobenzylthioinosine-sensitive equilibrative nucleoside transport. Their
      transport activity, however, was only about 10% of that observed in many other
      mammalian cell lines. This low transport activity correlated with a relatively
      low number of high-affinity nitrobenzylthioinosine binding sites (5 x
      10(3)/cell). Furthermore, although the equilibrative transporter of PK-15 cells
      exhibited a similar broad substrate specificity as the equilibrative nucleoside
      transporters of other mammalian cells, it exhibited a much higher affinity for
      certain nucleosides, especially cytidine and uridine, than the latter. The
      Michaelis-Menten constants for zero-trans transport and equilibrium exchange of
      uridine in ATP-depleted cells were about the same (about 40 microM), indicating
      equal mobility of the nucleoside-loaded and empty carrier. Concentrative
      nucleoside transport was detected in one set of PK-15 cultures, but was found to
      be due to mycoplasma contamination.

PMID- 1379471
TI  - Monoclonal antibodies against defined epitopes of the human transferrin receptor
      cytoplasmic tail.
AB  - Three murine monoclonal antibodies (mAbs) against the 61-residue amino-terminal
      cytoplasmic tail of the human transferrin receptor (TR) have been produced by
      immunization of mice with recombinant human TR produced in a baculovirus
      expression system. Mutant human TRs expressed in chick embryo fibroblasts (CEFs)
      with point mutations or deletions in their cytoplasmic tails have been used to
      map the epitopes defined by each of the mAbs. One mAb, H68.4, previously shown to
      block receptor internalization, binds proximal to the carboxy-terminal side of
      the YTRF internalization signal of TR. The second mAb, H73.2, binds near to the
      carboxy-terminal side of the H68.4 epitope, whereas the third mAb, 160.1, binds
      closer to the transmembrane region. H68.4 and H73.2 are auto-antibodies
      consistent with their epitopes mapping to a region of the human TR that has an
      identical amino acid sequence to the mouse TR. All three mAbs crossreact with the
      cytoplasmic tail of Chinese hamster TR. Double labelling of recombinant human TRs
      on chick embryo fibroblast (CEF) cell membrane preparations with B3/35 and H68.4
      antibody-gold conjugates established that receptors in clathrin-coated pits were
      not labeled with H68.4, implying that associated coated pit proteins may block
      binding of this mAb.

PMID- 1379472
TI  - Inhibitors of protein and RNA synthesis block the cytotoxic effects of oxygenated
      sterols.
AB  - Oxygenated derivatives of cholesterol are known to exhibit potent cytotoxic
      effects against many different cell types. The cellular basis of this
      cytotoxicity is not understood. Using two murine cancer cell lines (the EL4
      lymphoma and the K36 leukemia cell line) and two oxygenated sterols (7
      ketocholestanol and 25-hydroxycholesterol), our laboratory attempted to determine
      whether the cytotoxic action of oxysterols was mediated by a mechanism requiring
      protein or RNA synthesis. The addition of 5 microM 7-ketocholestanol or 25
      hydroxycholesterol to the culture medium regularly caused the viable cell count
      to fall below 10-20% of control within 48-72 h. In the presence of inhibitors of
      protein or RNA synthesis, however, cell viability was consistently and
      significantly increased in a dose-dependent manner. For cultures of EL4 cells
      grown in the presence of 5 microM 7-ketocholestanol, for example, the addition of
      appropriate concentrations of cycloheximide, puromycin, emetine, and actinomycin
      increased the percentage of viable cells from a control value of less than 6% to
      66%, 28%, 76% and 42%, respectively. Qualitatively similar results were obtained
      with the K36 cell line. Additional studies revealed that macromolecular synthesis
      inhibitors, while effective in inhibiting protein or RNA synthesis to varying
      degrees, did not affect the cellular uptake of 7-keto[3H]cholestanol, suggesting
      that their ability to protect cells against oxysterol-induced cytotoxicity was
      not due to an inhibition of the cellular oxysterol uptake. These observations
      suggest that the cytotoxicity of oxygenated sterols may be mediated by mechanisms
      requiring de novo protein or RNA synthesis and that oxysterol-induced
      cytotoxicity may provide a useful system for the identification of proteins
      involved in cell death.

PMID- 1379473
TI  - Correction of the apical membrane chloride permeability defect in polarized
      cystic fibrosis airway epithelia following retroviral-mediated gene transfer.
AB  - We are studying the introduction and expression of the normal cystic fibrosis
      transmembrane conductance regulator (CFTR) cDNA into cultured human airway
      epithelial cells as a model for gene therapy of cystic fibrosis. In this paper,
      we show that the chloride transport defect at the apical membrane is corrected in
      vitro in differentiated ion-transporting CF airway epithelial cells that exhibit
      polarized properties similar to those found in vivo. Using a retroviral vector
      containing a copy of the normal CFTR cDNA, we infected cultures of proliferating,
      cystic fibrosis CFT1 cells and found that correction was maintained following
      differentiation into a polarized epithelial sheet. At least partial correction of
      the Cl- transport defect was preserved in CFT1 cells for periods of up to 6
      months without selection for maintenance of the retroviral provirus. These
      results suggest that it may be feasible to target proliferating cells in the lung
      using retroviral vectors for treatment of CF lung disease.

PMID- 1379474
TI  - Haplotypes in SS patients from Nigeria; characterization of one atypical beta S
      haplotype no. 19 (Benin) associated with elevated HB F and high G gamma levels.
AB  - We have determined the haplotypes of 669 beta S and 109 beta A chromosomes from
      numerous members of 297 Nigerian families of various ethnic backgrounds. Among
      the beta S chromosomes, haplotype 19 was detected in 93.2%, haplotype 17 in 3.4%,
      and haplotype 20 in 0.1%, while 2.4% represented atypical haplotypes. As many as
      60.6% of the beta A chromosomes exhibited haplotype 19 mutations, 8.2% had
      haplotype 3, and 1.8% had haplotype 20. Two siblings with elevated Hb F and G
      gamma levels were heterozygous for a beta S chromosome with haplotype 19 and a
      second chromosome with a hybrid haplotype (termed 19 B). In this hybrid
      chromosome, haplotype 3-like locus control region (LCR) [hypersensitive site-2
      (HS-2)] sequences are in juxtaposition to those of the 5' flanking region of the
      G gamma promoter of a beta S chromosome with haplotype 19. The presence of this
      hybrid chromosome is associated with high G gamma values in individuals with both
      sickle cell anemia (SS) and sickle cell trait (AS); it closely resembles another
      hybrid beta S chromosome, termed 19 A, observed in a previously reported Turkish
      SS patient who was homozygous for this chromosome and had high Hb F and high G
      gamma values. In both instances, it is hypothesized that the haplotype 3-like
      sequences of the LCR HS-2 contain genetic determinants that can combine with
      factors produced during hematopoietic stress, resulting in increased gamma-globin
      gene expression.

PMID- 1379475
TI  - Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on
      circulating platelets.
AB  - The effect on platelets of rhG-CSF was studied in 20 healthy volunteers with the
      thrombometer, a specially developed device which is described in detail.
      Additionally, conventional aggregation tests were performed. Low doses of rhG-CSF
      enhance functional platelet activity, as shown by significant acceleration of the
      occlusion of the thrombometer channel. Similar results were found in conventional
      aggregation tests utilizing collagen for induction. At G-CSF concentrations of
      0.1 and 1.0 ng/ml the time to response was significantly accelerated and the
      maximum response was observed in a higher proportion of platelets. However, the
      second phase of aggregation induced by epinephrine was significantly inhibited by
      1.0 ng/ml G-CSF. The activation of platelets may be beneficial in
      thrombocytopenia, but it may also increase platelet turnover and platelet loss.
      Further investigation is needed to clarify the mechanism by which G-CSF exerts
      its effects on platelets.

PMID- 1379476
TI  - Feline interferon production in silkworm by recombinant baculovirus.

PMID- 1379477
TI  - Enzyme-linked immunosorbent assay (ELISA) using urease-conjugated antibodies for
      Toxoplasma antibody detection.

PMID- 1379478
TI  - Prevention of estrus in the bitch with chlormadinone acetate administered orally.

PMID- 1379479
TI  - Renewal and differentiation of keratinocytes cultured on dead de-epidermalized
      dermis.
AB  - Human keratinocytes grown at an air-liquid interface on dead de-epidermalized
      dermis exhibit a pattern of organization similar to that seen in vivo. Cell
      renewal is limited to the basal layer. The cell cycle time determined after 7
      days of culture, using a percentage labelled mitoses (PLM) technique, was about
      15 h. This result is comparable with published data for cultivated keratinocytes
      but is shorter than the parameter proposed for epidermis in vivo. Appearance of
      labelled cells in the granular layer was observed 4 days after pulse labelling.
      Despite this high cell renewal, a normal cell differentiation with expression of
      various keratinization markers was maintained.

PMID- 1379480
TI  - Prostacyclin-mediated protection by angiotensin-converting enzyme inhibitors
      against injury of aortic endothelium by free radicals.
AB  - We report here the protective effect of the angiotensin converting enzyme
      inhibitors captopril and ramiprilat against damage due to oxygen free radicals on
      aortic endothelium in a superfusion cascade system. Oxygen free radicals were
      generated by electrolysis of Krebs solution. Acetylcholine was infused through
      the donor aortic segment and relaxation of the detector aortic ring was used to
      indicate the release of endothelium-derived relaxing factor (EDRF). The
      percentage of relaxation before and after electrolysis was compared to calculate
      the relaxation index. Electrolyzed Krebs solution impaired the release of EDRF,
      as shown by a reduction in the relaxation index with a concomitant decrease in
      the tissue levels of superoxide dismutase and 6-keto PGF1 alpha and increase in
      malondialdehyde in the donor vessel. Captopril (100 microM), 15 microM ramiprilat
      and 30 nM iloprost had a protective effect as shown by a significantly smaller
      reduction in the relaxation index and the level of 6-keto PGF1 alpha and by an
      attenuation of the production of malondialdehyde. In addition, 1 microM
      indomethacin almost eliminated the protection by captopril. We conclude that both
      the SH-containing angiotensin-converting enzyme inhibitor captopril and the non
      SH-containing ramiprilat, as well as iloprost, a stable analog of prostacyclin,
      can protect rabbit aortic endothelium against damage due to oxygen free radicals.
      The mechanism of such protection may be partly associated with the facilitation
      of the release of prostacyclin and consequent reduction in lipid peroxidation.

PMID- 1379481
TI  - Ionic currents in ventricular myocytes isolated from the heart of a patient with
      idiopathic cardiomyopathy.
AB  - Whole-cell configuration of the patch-clamp technique was applied to record ionic
      currents from human ventricular myocytes isolated from a cardiac transplant
      patient with idiopathic cardiomyopathy. Inward calcium current, transient outward
      current, and inward rectifier potassium current were recorded, while no
      discernible delayed rectifier potassium current was observed. Thus the currents
      that underlie electrical activity in human ventricular myocytes appear to
      resemble those reported earlier in canine and rabbit ventricular myocytes.

PMID- 1379482
TI  - A predictive model for substrates of cytochrome P450-debrisoquine (2D6).
AB  - Molecular modeling techniques were used to derive a predictive model for
      substrates of cytochrome P450 2D6, an isozyme known to metabolize only compounds
      with one or more basic nitrogen atoms. Sixteen substrates, accounting for 23
      metabolic reactions, with a distance of either 5 A ("5-A substrates", e.g.,
      debrisoquine) or 7 A ("7-A substrates", e.g., dextromethorphan) between oxidation
      site and basic nitrogen atom were fitted into one model by postulating an
      interaction of the basic nitrogen atom with a negatively charged carboxylate
      group on the protein. This acidic residue anchors and neutralizes the positively
      charged basic nitrogen atom of the substrates. In case of "5-A substrates" this
      interaction probably occurs with the carboxylic oxygen atom nearest to the
      oxidation site, whereas in the case of "7-A substrates" this interaction takes
      place at the other oxygen atom. Furthermore, all substrates exhibit a coplanar
      conformation near the oxidation site and have negative molecular electrostatic
      potentials (MEPs) in a part of this planar domain approximately 3 A away from the
      oxidation site. No common features were found in the neighbourhood of the basic
      nitrogen atom of the substrates studied so that this region of the active site
      can accommodate a variety of N-substituents. Therefore, the substrate specificity
      of P450 2D6 most likely is determined by the distance between oxidation site and
      basic nitrogen atom, by steric constraints near the oxidation site, and by the
      degree of complementarity between the MEPs of substrate and protein in the planar
      region adjacent to the oxidation site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379483
TI  - Ion channels for communication between and within cells.
AB  - The development of patch-clamp procedures for measuring single-channel current
      fluctuations are described. The application of these techniques for studying
      secretion is discussed.

PMID- 1379484
TI  - Identification of a nuclear-encoded sunflower mitochondrial tRNA-Leu (AAG).

PMID- 1379486
TI  - The respiratory sensation at high altitude.
AB  - The respiratory sensation was studied in Nepal at four different altitudes, 1377
      m before and after the ascension, 2800 m, 3900 m and 530 m. Dyspnea was noted at
      each altitude for the nine subjects. They had to rate 4 external resistive loads
      between 2.5 and 13 cm H2O.l-1.s, presented in 2 pairs, a low and a high one. The
      discrimination between the loads i.e. the subject's sensitivity was obtained from
      Sensory Decision Analysis. These subjects were compared to six normal ones
      observed at sea level while breathing air, an hypoxic mixture (FIP2:11%) and air
      in a cold environment (-6 degrees C). In these protocols, the load perception was
      not modified. The 2 populations exhibited a similar sensitivity when observed in
      normal conditions. At exertion and with altitude, the nine subjects demonstrated
      a progressive increase in dyspnea, rated with visual analog scales. At rest, the
      perception of the loads was not altered but slightly improved with altitude for 6
      subjects. The other 3 subjects (2 subjects with clinical impairment, important
      dyspnea and pulmonary oedema) showed an impairment of the perception. The
      sensitivity to the loads was similar before and after the ascension for the well
      adapted subjects to altitude. In conclusion, the respiratory sensation is not
      impaired with altitude in well adapted subjects and transient hypoxia does not
      result in change in load perception. An impairment in load perception observed in
      some subjects is probably related to the secondary effects of chronic hypoxia,
      i.e. cerebral and/or pulmonary suboedema.

PMID- 1379485
TI  - Changes in microsomal phospholipid fatty acids composition in cholestatic rats.
AB  - In the rat, the effect of the bile duct ligation on liver microsomal phospholipid
      fatty acid composition and on phosphatidylcholine, phosphatidylserine and
      phosphatidylinositol pattern were studied. After two days of cholestasis,
      microsomal phospholipid fatty acids showed a decrease in linoleic, stearic and
      arachidonic acids and an increase in oleic and docosahexaenoic ones, as compared
      to controls. Phosphatidylcholine showed an increment in oleic and palmitic acid
      content and a concomitant decrease in arachidonic acid. Phosphatidylserine showed
      a progressive increase while phosphatidylinositol showed a progressive decrease
      in all fatty acids. Eight-days post-cholestatic rats showed a marked increase in
      oleic acid, whereas linoleic, arachidonic, stearic and palmitic acids
      concentration decreased. Phosphatidylcholine showed a global decrease in its
      fatty acid content, except for oleic which is increased. Phosphatidylserine
      showed an increase over the two-days cholestasis fatty acids values.
      Phosphatidylinositol decreased in most fatty acids except in docosahexaenoic acid
      that recovered normal values. It was concluded that cholestasis produced
      significative changes in the fatty acid composition of the major phospholipids
      constituents of the microsomal membranes.

PMID- 1379487
TI  - Cardiovascular and hormonal responses to ANP infusion in the guinea-pig: effects
      of angiotensin-converting enzyme inhibition with perindopril.
AB  - In the guinea-pig, perindopril inhibited plasma angiotensin converting enzyme
      (ACE) by 90% when given orally at 2 mg/kg/day during 10 days. Mean blood pressure
      and plasma aldosterone, cortisol and vasopressin concentrations were not modified
      by this treatment, while plasma renin activity (PRA) and plasma angiotensin I
      concentrations increased significantly. The same parameters were studied using a
      constant intravenous 30 min-infusion of atrial natriuretic peptide (ANP) (0.1
      micrograms.kg-1min-1). This dose of ANP infused to anesthetized guinea-pigs
      induced a significant decrease in mean blood pressure (about -20%) in control and
      in perindopril treated animals. In ANP infused animals, plasma aldosterone and
      cortisol concentrations decreased similarly in both groups by about -50%, whereas
      plasma vasopressin concentrations increased in controls (+169%) but not in
      perindopril treated guinea-pigs. An increase in PRA and plasma angiotensin I
      concentrations was observed in both groups after the infusion of ANP. Thus, when
      ANP demonstrated an potent hypotensive effect a concomitant increase in PRA
      occurred. The rise observed in vasopressin concentration in control animals was
      probably mediated by angiotensin II. The fall in plasma aldosterone and cortisol
      concentrations observed after ANP infusion demonstrated a direct potent action of
      ANP at the adrenal levels.

PMID- 1379488
TI  - The neonatal testosterone surge: a comparative study.
AB  - In the rat an abrupt discharge of testicular testosterone in the newborn male
      figures prominently in the development of mechanisms controlling gonadotropin
      secretion, sexual behavior, and also promotes the functional differentiation of
      the accessory sex glands. In this study we detail the temporal characteristics of
      this surge in the rat, and we provide comparative data documenting a similar
      surge-like appearance of testosterone in neonatal male mice, recently foaled male
      horses, and newborn human infants. Although the physiological and behavioral
      significance of this phenomenon for species other than the rat remains to be
      determined, the apparently ubiquitous appearance of the neonatal testosterone
      surge suggests that it may be of special significance in the sexual
      differentiation of many mammalian species.

PMID- 1379489
TI  - Induction in Gallus domesticus of experimental hypercholesterolemia by saturated
      fat. Effects on cholesterogenic enzyme activity.
AB  - The effect of coconut oil supplementation to the diet (10 or 20%) on lipid levels
      in plasma and liver as well as on the cholesterogenic enzyme activity were
      studied in 14-day-old chicks. Treatments for 1 or 2 weeks did not interfere in
      the growth rate of animals nor in the liver weight. The 10% coconut oil group
      showed a significant increase of plasma cholesterol after 2 weeks of treatment,
      while after 1 week the increase was not statistically significant. The 20%
      coconut oil group increased plasma cholesterol from the first week.
      Triacylglycerol content increased after each coconut oil supplementation to the
      diet during the first week. Hepatic cholesterol did not change significantly
      after any treatment assayed. No significant difference was observed in the
      cholesterogenic activity, measured as hepatic 3-hydroxy-3-methylglutaryl-CoA
      reductase, so that this study provides a perfect model of hypercholesterolemic
      animals without changes in their cholesterogenic ability.

PMID- 1379490
TI  - Dietary sucrose supplementation fails to modify fat deposition in lean or obese
      rats.
AB  - The effects of sucrose supplementation on body composition and heat production
      were studied in lean, dietary (cafeteria diet) and genetically (Zucker fa/fa)
      obese adult (60 days) rats. Sucrose supplement (29 kJ) for 10 days did not result
      in significant changes in the pattern of energy (fat) deposition or carcass
      composition. There were no alterations, either, in heat production measured by
      direct calorimetry. Under the conditions studied, sucrose intake did not affect
      lipid deposition or thermogenesis.

PMID- 1379491
TI  - Effect of naloxone-reversible immobilization stress on the adrenal
      acetylcholinesterase activity in mice.
AB  - In male mice immobilized during 30 min, statistically significant increase in
      adrenal acetylcholinesterase (Ache) activity--up to 154% of control value--has
      been observed. Naloxone pretreatment (10 mg/kg b.w., ip.) suppressed that
      increase, Ache activity remaining at the level of non-immobilized, saline treated
      mice. This suggests the role of opioid peptides in this change. Ganglionic
      blockade by hexamethonium markedly inhibited Ache activity in adrenals of non
      immobilized and of immobilized mice. Opioid peptides secreted from the splanchnic
      nerve terminals seem to be involved in the control of cholinergic mechanisms.

PMID- 1379492
TI  - Tissue composition in persistent dietary obesity after early and adulthood
      overfeeding in the rat.
AB  - The objective of this study was to assess the effects of prolonged cafeteria-diet
      feeding on tissue composition in adult rats comparing those that had been overfed
      in early life and then in adulthood with a group that was only overfed in
      adulthood, and to determine whether any alterations were related to the high
      energy diet per se or to obesity. In addition to following the body weight
      changes in detail, tissue masses and composition were determined at selected
      points of this long term dietary experiment. The marked changes in body weight
      and tissue composition of cafeteria-fed obese rats were sustained for at least 84
      days after returning to the standard diet, and the obesity was exaggerated if
      these animals were pre-exposed to the palatable diet in early life. Three
      patterns of tissue composition in response to cafeteria feeding could be
      discerned: Liver and brown adipose tissue developed cell hypertrophy without
      apparent hyperplasia. In contrast, the retroperitoneal white adipose depot
      developed hyperplasia whereas the intestine and kidneys were not associated with
      marked changes in lipid composition. These adaptations were not recovered to
      control levels by prolonged standard diet feeding. Previous obesity influenced
      the adaptations in adipose tissue during the subsequent return to standard diet
      feeding, and differences between cafeteria-induced obese animals became more
      apparent when the cafeteria diet was removed. These results indicated the
      important effects of early dietary experience in subsequent responses to
      overfeeding.

PMID- 1379494
TI  - Heterogeneity of 5-HT responsiveness in different segments of rabbit arteries.
AB  - The variation in sensitivity to serotonin (5-HT) as assessed by pD2 was
      investigated in isolated 25 arterial segments of different vascular regions
      obtained from rabbits. The responses of the vascular rings which were opened by a
      transverse cut to form rectangular strips were recorded isometrically. pD2 values
      for 5-HT of thoracic and abdominal aortic segments were significantly greater
      than those of visceral arterial branches. Maximal contractions produced by 5-HT
      in visceral segments were higher than those of thoracic and abdominal aortic
      segments. There was a positive correlation between the pD2 values for 5-HT and
      the radii and the thickness of the tunica media layer (r = 0.62 and r = 0.54,
      respectively, P less than 0.05). The results indicate that the activity of 5-HT
      varies regionally in different segments of the rabbit arteries and the
      sensitivity to 5-HT of the segments decreases as the radii of the vessels
      diminish.

PMID- 1379493
TI  - Effect of starvation on the in vivo intestinal absorption of sugars and amino
      acids in young chickens (Gallus domesticus).
AB  - The effect of different patterns of starvation (acute and intermittent) on the in
      vivo intestinal absorption of glucose and tryptophan during the first days of
      Gallus domesticus chicks life was measured. Both acute and intermittent
      starvation increase duodenal absorption of glucose and jejunal absorption of
      tryptophan. Intermittent starvation tends to reduce the effect of age which
      normally decreases intestinal uptake of nutrients. This effect is clearer for
      glucose absorption than for tryptophan absorption.

PMID- 1379495
TI  - Hormonal induction of c-fos and HSP68 mRNAs on an isolated coronary perfused
      adult rat heart.
AB  - Transient growth signals which can be related to protein synthesis and cellular
      growth are of particular interest in the heart because of the incidence of
      cardiac hypertrophy in man. The isolated coronary perfused adult rat heart or the
      so-called Langendorff preparation, is an useful model in exploring not only
      protein synthesis but also c-fos/c-myc protooncogene and Heat Shock Protein (HSP)
      gene expression. Phenylephrine infusion in this preparation induces c-fos
      expression whether the heart is beating or reversibly or irreversibly arrested by
      solutions enriched in KCl. Norepinephrine has the same effect. Quantitative
      analysis with slot blots shows that in both cases the adrenergic effect has a
      dual origin since it is inhibited both by propranolol, a beta-adrenergic
      antagonist, and terazosine, a soluble alpha 1-adrenergic antagonist. We conclude
      that the isolated heart is a useful tool to explore the early changes in gene
      expression which occur in this tissue in response to various physiological
      stimuli.

PMID- 1379496
TI  - Influence of thyroid hormone deficiency in DNA contents in different areas of
      adult rat brain.
AB  - We have studied DNA concentrations in various regions of the adult rat brain in
      prolonged hypothyroidism of different origin. In both normal and hypothyroid rats
      hypophysis, cerebellum and hypothalamus contained the highest concentrations of
      DNA. Hypothyroidism produced a slight decrease in DNA content but this effect
      varied according to the different regions. These variations were due to changes
      in their maturation period, a critical and specific target for thyroid hormone
      action after birth.

PMID- 1379497
TI  - Biochemical characterization of particles from rat striatum containing dopamine,
      cholecystokinin or both.
AB  - Cholecystokinin (CCK) containing particles were isolated from rat striatum. After
      differential and isopycnic sucrose density gradient centrifugation, CCK
      containing particles equilibrated around 1.2 M sucrose. Dopamine (DA) containing
      particles equilibrated around the same buoyant density, but the colocalization of
      a cytosolic as well as a mitochondrial enzyme marker and the low enrichment at
      this density indicated an incomplete isolation of CCK containing particles from
      other subcellular organelles. Alternatively, differential centrifugation and gel
      filtration on Sephacryl S-1000 did yield advanced isolation of CCK containing
      vesicles. These vesicles also contain particle-bound DA. During hypo-osmotic
      lysis, these CCK and/or DA containing particles behaved like synaptic vesicles.
      Therefore, it was concluded that CCK containing vesicles from rat corpus striatum
      were indeed isolated and characterized and that the same or similar vesicles
      contain DA as well as CCK.

PMID- 1379498
TI  - [Simple and generalized first order differential equations. Their use in a few
      macrophysiology domains].
AB  - First order differential equations formulate the simplest physiological models
      and, therefore, are endowed with wide applicability. They owe this advantage to
      the principle of parcimony: according to Occam's razor, the most general
      explanations are a priori the best. First order equations express the essential
      properties of the system. However, they often are inappropriate for representing
      complementary facts characteristic of the real objects. Any refinement of the
      model requires the inclusion of higher order terms. Our goal is to arrive at a
      general method for addressing a variety of problems. Here, we chose the example
      of the Windkessel model to introduce the mathematical framework. The input was
      simplified without loss of generality. We also proposed a possible analytical
      approach and compared its results with those of the numerical methods. This led
      to the improvement of the latters. Finally, some prominent examples in the field
      of macrophysiology were discussed.

PMID- 1379499
TI  - Assignment of mouse alpha-2-macroglobulin gene to chromosome 6 band F1-G3.

PMID- 1379500
TI  - [Changes in lymph microcirculation in appendicular peritonitis].
AB  - When studied in experiment (63 dogs) and in clinical settings (116 patients),
      microlymphatic channel in appendicular peritonitis (AP) was found impaired, while
      lymphatic drainage of large-molecular substances and metabolites coming from the
      abdominal cavity appeared activated. Methods of correction of AP-induced
      abnormalities in microlymphocirculation have been developed which imply three
      levels of the impact: microcirculation, affected organ, lymphatic system. The
      clinical trial of the methods proved their efficacy even in the most severe AP
      forms.

PMID- 1379501
TI  - GABAA receptor channels: from subunits to functional entities.
AB  - GABAA receptor channels mediate postsynaptic inhibition. The functional diversity
      of these receptors rests on differences in subunit composition and on a large
      repertoire of subunits. Subunit expression patterns in the brain have been found
      to predict in vivo compositions of GABAA receptors. In addition, molecular
      determinants underlying the differential binding properties of allosteric ligands
      to receptor subtypes have been identified.

PMID- 1379502
TI  - Human thymic epithelial cells in serum-free culture: nature and effects on
      thymocyte cell lines.
AB  - Thymic epithelial cells (TEC) have been cultured for several months and/or for 4
      to 5 transfers in a growth factor-defined serum-free medium without concurrent
      growth of other cell types. The use of monoclonal antibodies and alpha MAM-6
      indicated that the majority of TEC were of medullary origin. The vast majority of
      cells were positive for LFA-3 and class I, and class II expression was low or
      absent. Supernatants from the cultures were shown to contain IL-1 beta, IL-6, and
      M-CSF. Coculture of cloned subpopulations of thymocytes and TEC showed effects of
      TEC and of secreted ILs on thymocyte proliferation. High percentages of TEC were
      able to bind DN, DP, or SP thymocyte populations, partly via CD2-LFA-3 adhesion.
      Thus, it is possible to culture TEC without unknown serum factors and with
      maintenance of functional activities.

PMID- 1379503
TI  - A striational muscle antigen and myasthenia gravis-associated thymomas share an
      acetylcholine-receptor epitope.
AB  - The coincidence of autoantibodies against the acetylcholine receptor (AChR) and
      muscle striational antigens (SA) is a characteristic finding in thymoma
      associated myasthenia gravis (MG), but their origins are still unresolved. Some
      common muscle antigens that were shown to be targets of anti-SA autoantibodies in
      thymoma-associated MG have also been detected in normal or neoplastic thymic
      epithelial cells, suggesting that the release of (eventually altered) antigens
      from the thymic tumors could elicit SA autoimmunity. In contrast to this model,
      we report here that titin, which is a recently reported target of SA
      autoimmunity, is not expressed in thymomas. In addition, we show that skeletal
      muscle type-II fibers exhibit a striational immunoreactivity with monoclonal
      antibody mAb155, which was previously identified to label a very immunogenic
      cytoplasmic epitope of the AChR and neoplastic epithelial cells of MG-associated
      thymomas. We conclude from these findings that titin autoimmunity in thymoma
      associated MG is either due to a molecular mimicry mechanism involving tumor
      antigens (other than titin) or is a secondary phenomenon following release of
      titin from muscle. Based on the common immunoreactivity of the AChR, a
      striational antigen and thymoma, we suggest as the pathogenetic mechanism of
      thymoma-associated MGa "circulus vitiosus" in which SA autoimmunity could help
      maintain the AChR autoimmunity that is primarily elicited by the thymomas.

PMID- 1379504
TI  - Antigenic analyses of Sugi basic protein by monoclonal antibodies: I.
      Distribution and characterization of B-cell-tropic epitopes of Cry j I molecules.
AB  - Using 23 monoclonal antibodies raised against Sugi basic protein (SBP, major
      allergen of Japanese cedar pollen), composed of Cry j I and Cry j II, analyses of
      B-cell-tropic epitopes of Cry j I were performed. The following results were
      obtained. (1) As far as the mAbs were used, no major cross-reactive determinants
      were detected between Cry j I and Cry j II molecules. (2) 21 of the 23 mAbs were
      specific for Cry j I, and the anti-Cry j II mAbs were classified into four groups
      by their fine specificities, suggesting that Cry j I bears at least four
      antigenic determinant regions. (3) Cry j I molecules were found to take a
      monomeric form in solution and to display no repeating antigenic epitopes on
      their surfaces. (4) Some of the determinants seemed to be located in the interior
      of a Cry j I molecule, and when the Ag is coated on a plastic plate, the
      determinants become exposed on its surface. (5) Binding of human IgE antibodies
      to Cry j I and Cry j II was blocked by some of the obtained mAbs, suggesting that
      these epitopes recognized by the mAbs might have an important role in human
      allergic response against the cedar pollen.

PMID- 1379505
TI  - Antigenic analyses of Sugi basic protein by monoclonal antibodies: II. Detection
      of immunoreactive fragments in enzyme-cleaved Cry j I.
AB  - The 4 anti-Cry j I mAbs showing an epitope specificity different from each other,
      046, 029, 026 and 027, were selected to analyze the structure of the antigenic
      determinant for each mAb on a Cry j I molecule. Immunoreactive fragments in
      enzyme-cleaved Cry j I were detected by means of the adsorption on the mAb column
      and of the binding to the mAbs on Elisa. The mAb 026 was found to be reactive to
      the fragments containing a Cry j I N-terminal region obtained by V8 protease or
      pepsin digestion, but not to those by lysylendopeptidase digestion. The mAb 027
      was found to be capable of binding to the fragments containing a linear structure
      of Asn-Ala-Gly-Val-Leu-Thr-Cys-Ser-Leu-Ser-Lys, which were generated by V8
      protease, lysylendopeptidase or pepsin digestion. Furthermore, the synthetic
      peptide Asn-Ala-Gly-Val-Leu-Thr-Cys-Ser- Leu-Ser-Lys-Arg could bind to 027, but
      not to 026, and could inhibit the binding of 027 to Cry j I or to its
      immunoreactive fragments. No fragments capable of reacting to the mAbs 046 and
      029 could be found in this study, suggesting that 046 and 029 recognize a
      conformationally constituted epitope of Cry j I molecule which is destroyed by
      enzymatic cleavage. The epitope recognized by the mAbs 027 or 026 was found to be
      located in conformationally hidden parts of the molecule which was exposed to
      react to the mAbs only after the physicochemical or enzymatic treatment.

PMID- 1379506
TI  - Antiallergic activity of 6-(2-cyclohexylethyl)-[1,3,4]thiadiazolo- [3,2-a]-1,2,3
      triazolo-[4,5-d]pyrimidin-9(3H)-one (DS-4574) in rats.
AB  - The antiallergic activity of DS-4574 was evaluated in several commonly used rat
      models for allergic diseases. In passive cutaneous anaphylaxis, DS-4574 given
      intravenously and orally induced dose-dependent inhibition with ID50 values of
      0.55 and 2.8 mg/kg, respectively. In contrast, this compound had no antagonistic
      activity against the histamine- and serotonin-induced cutaneous vascular
      permeability. In lung anaphylaxis, DS-4574 inhibited pulmonary function changes
      induced by the antigen in a dose-dependent manner when it was given intravenously
      and orally, the ID50 values being 0.04 and 0.89 mg/kg, respectively. DS-4574 also
      inhibited antigen-induced histamine and leukotriene release in passive peritoneal
      anaphylaxis following oral administration. In addition, this compound prevented
      antigen-induced histamine release in passively sensitized mast cells in vitro.
      These potent activities of DS-4574 in in vivo and in vitro models of immediate
      type hypersensitivity reactions suggest that this compound could be useful in the
      treatment of allergic diseases including asthma.

PMID- 1379507
TI  - Development of Hodgkin's disease in the course of primary Sjogren's syndrome.
AB  - We report two patients with a definite diagnosis of primary Sjogren's syndrome
      who developed Hodgkin's disease. Clinical and laboratory features of this
      transformation comprised prolonged fever, the appearance of lymphadenopathy
      together with loss of serum autoantibodies and a reduction in serum gammaglobulin
      levels. We know of only one well documented case of such an association. From
      these observations, it seems reasonable to include Hodgkin's disease in the
      clinical spectrum of the lymphoproliferative disorders that may occur in the
      course of primary Sjogren's syndrome.

PMID- 1379508
TI  - Elective versus emergency surgery for patients with colorectal cancer.
AB  - A prospective study of 570 patients presenting with colorectal cancer over a 6
      year period was undertaken. Of these, 363 were admitted electively and 207
      presented as emergencies. The outcome following elective admission was more
      favourable than after emergency admission. In the elective group the proportion
      of resected tumours was greater (77 versus 64 per cent, P less than 0.001), the
      operative mortality rate lower (9 versus 19 per cent, P less than 0.001) and the
      5-year disease-related survival rate higher (37 versus 19 per cent, P less than
      0.001). These differences may relate to the greater resection rates in the
      elective situation. Results of surgical intervention might be improved if
      emergency colorectal operations were undertaken by surgeons with more experience
      of this type of surgery.

PMID- 1379510
TI  - Symptom control in terminal illness.

PMID- 1379509
TI  - Post-hatching developmental changes in the ultrastructure of the duodenal
      absorptive epithelial cells in 1, 10 and 60-d-old chickens, with special
      reference to mitochondria.
AB  - 1. Post-hatching developmental changes in the ultrastructure, cell area and
      histological RNA content of duodenal absorptive epithelial cells were observed in
      1, 10 and 60-d-old White Leghorn (WL) and broiler (BR) chickens, with special
      reference to the mitochondria (Mt). 2. Epithelial cells in 1-d-old WL and BR had
      a well-developed Golgi area and a dense cluster of rod type Mt near the cell
      surface and at the infranuclear region. In BR, cells included well developed
      profiles of endoplasmic reticulum but fewer supranuclear vacuoles than those of
      WL, in which numerous free ribosomes were also found. Some Mt in BR showed a bud
      like protrusion from the main body (tadpole type Mt). These suggest that the fine
      structural maturation of the epithelial cells in WL is involved in the process of
      cell maturation but epithelial cells of BR have almost matured at hatching. 3. In
      10-d-old WL and BR, supranuclear vacuoles had disappeared and Mt increased in
      number. In WL, in addition to a decrease in free ribosomes, Mt developed to the
      tadpole type and further to dumbbell type ones. In BR, Mt also aggregated at the
      perinuclear region and some of them had developed from dumbbell shapes to a thick
      doughnut type. These findings indicate that epithelial cells in both breeds are
      more developed ultrastructurally than those in 1-d-old and that epithelial cells
      in BR are more activated for digestive and absorptive functions than those in WL.
      4. In 60-d-old WL and BR, Mt showed various types with thinner matrices than 10-d
      old, suggesting that the cell structure and function had reached a stable state.
      5. BR revealed higher values for cell area and RNA content than WL at every age
      and RNA content of both breeds were maximal at 10 d, followed by 60 d. 6. Mt
      changed their shapes from rod type to tadpole type. The latter then developed to
      doughnut type via dumbbell type, related to an increase of epithelial cell
      functions. 7. Epithelial cells of BR are thus more highly activated than WL cells
      at each age and reach morphological and physiological maturation around 10 d.

PMID- 1379511
TI  - Mechanism for the recruitment of macrophages to cancer site. In vivo
      concentration gradient of monocyte chemotactic activity.
AB  - BACKGROUND: Tumor stroma is characterized by the development of new blood
      vessels, an inflammatory cell infiltration, and a fibrotic reaction. The
      inflammatory component of tumor stroma plays an important role in the modulation
      of tumor expansion. In this respect, macrophages constitute a major part of the
      inflammatory cell infiltration and can exert cytotoxic activity against tumor
      cells. The accumulation of macrophages in the vicinity of the tumor suggests
      their recruitment from circulating blood monocytes through the local release of
      chemotactic factors for monocytes. METHODS: To detect the existence of a
      concentration gradient of monocyte chemotactic activity (MCA) between the tumor
      vicinity and blood vessels, malignant pleural effusions defined by the local
      presence of cancer cells were evaluated for quantification of MCA. RESULTS:
      Unlike nonmalignant pleural effusions, malignant pleural effusions were
      characterized by the presence of increased levels of MCA, and in lung
      adenocarcinoma (a cancer with high inflammatory cell infiltration), pleural
      levels of MCA were significantly greater than in small cell lung carcinoma (a
      cancer with low inflammatory cell reaction). An MCA concentration gradient
      between pleural fluid and plasma was present in malignant effusions because
      pleural MCA levels in all cancer types were significantly greater than MCA levels
      in the plasma of the same patients. CONCLUSIONS: Thus, an increased local level
      of MCA is a feature of cancers with high inflammatory cell infiltration, and the
      presence of an in vivo concentration gradient of MCA suggests the direct role of
      this biologic activity in recruiting blood monocytes to the cancer site.

PMID- 1379512
TI  - Acute undifferentiated leukemia with CD7+ and CD13+ immunophenotype.

PMID- 1379513
TI  - Disposition characteristics of macromolecules in the perfused tissue-isolated
      tumor preparation.
AB  - Disposition characteristics of model macromolecules with different
      physicochemical characteristics and macromolecular prodrugs of mitomycin C,
      namely mitomycin C-dextran conjugates, were studied in tissue-isolated tumor
      preparations of Walker 256 carcinoma with the use of a single-pass vascular
      perfusion technique. In constant infusion experiments, all radiolabeled
      macromolecules accumulated in the tumor tissue, but the degree and pattern of
      distribution greatly varied, depending on their electric charges. Positively
      charged macromolecules were markedly accumulated compared with those that were
      neutral or negatively charged. In addition, their concentrations were
      significantly higher in viable than in necrotic regions, while neutral and
      negative compounds were distributed in necrotic rather than in viable regions.
      Pharmacokinetic analysis of tissue concentration-time courses of positively
      charged diethylaminoethyl and neutral dextrans showed that their movement
      occurred by convective fluid flow, and that high tissue accumulation of
      positively charged macromolecules could be explained by strong binding due to
      electrostatic interaction. For neutral and anionic macromolecules with negligible
      affinity to the tissue, it was suggested that the final concentration gradient
      between the viable and necrotic regions was decided by their tissue fluid
      content. Thus, the present study revealed the basic disposition characteristics
      of macromolecules in tumor tissue relative to their physicochemical properties.

PMID- 1379514
TI  - Cyclin D1 messenger RNA is inducible by platelet-derived growth factor in
      cultured fibroblasts.
AB  - In fibroblasts in culture, the levels of cyclin D1 mRNA are growth regulated. In
      mouse and in human fibroblasts, both serum and platelet-derived growth factor
      increase cyclin D1 mRNA levels with similar kinetics of induction. Insulin-like
      growth factor 1 by itself does not induce cyclin D1 expression, and an antisense
      oligodeoxynucleotide to the insulin-like growth factor 1 receptor RNA does not
      affect the growth-regulated levels of cyclin D1 mRNA.

PMID- 1379515
TI  - Broad spectrum neuropeptide antagonists inhibit the growth of small cell lung
      cancer in vivo.
AB  - The proliferation of small cell lung cancer (SCLC) cells appears sustained by
      multiple autocrine and paracrine circuits involving Ca2+ mobilizing
      neuropeptides. Consequently, broad spectrum neuropeptide antagonists which
      inhibit SCLC growth in vitro have been suggested as potential anticancer agents.
      Here we evaluated this hypothesis using xenografts of WX322 cells, a SCLC cell
      line that responds to multiple Ca2+ mobilizing neuropeptides. The broad spectrum
      neuropeptide antagonists [Arg6,D-Trp7,9,MePhe8]substance P(6-11) and [D-Arg1,D
      Phe5,Trp7,9Leu11[substance P were shown to inhibit the growth of WX322 xenografts
      in nude mice. Similar results were obtained with xenografts of the SCLC cell line
      H69. The results indicate that broad spectrum neuropeptide antagonists can
      inhibit the growth of SCLC in vivo and suggest that these antagonists could be
      useful in the treatment of SCLC.

PMID- 1379516
TI  - Synthesis of 3,6-dideoxy-4-C-(4(1)-hydroxyethyl)hexopyranoses (yersinioses) from
      1,6-anhydro-beta-D-glucopyranose.

PMID- 1379517
TI  - Synthesis of lysine-containing fragments of the Proteus mirabilis O27 O-specific
      polysaccharide and neoglycoconjugates therefrom.
AB  - Amide-linked lysine mono- and di-uronic acid fragments of the O-specific
      polysaccharide from P. mirabilis O27 have been synthesised. N epsilon-Boc-L
      lysine tert-butyl ester was condensed with 2-azidoethyl glycosides of glucuronic
      acid and beta-D-GlcpNAc-(1----3)-beta-D-GlcpA. Transformation of the products
      into 2-acrylamidoethyl glycosides, followed by deprotection using trifluoroacetic
      acid, gave the target monomers that were converted into high-molecular-weight
      copolymer-type neoglycoconjugates.

PMID- 1379518
TI  - Immunophilin-sensitive protein phosphatase action in cell signaling pathways.

PMID- 1379519
TI  - The polarity of editing within a multiple gRNA-mediated domain is due to
      formation of anchors for upstream gRNAs by downstream editing.
AB  - Seventeen kinetoplast minicircle-encoded and nine maxicircle-encoded gRNA genes
      have been identified. Six overlapping minicircle-encoded gRNAs mediate editing
      for the 5'-pan-edited MURF4 gene and two for the 5'-edited COIII gene. The pan
      edited RPS12 mRNA is edited by seven minicircle-encoded gRNAs and one maxicircle
      encoded gRNA. The 3'-most gRNA in each domain forms an anchor with unedited mRNA,
      whereas upstream gRNAs form anchors only with edited mRNA, thereby explaining the
      observed 3' to 5' polarity of editing within an editing domain. We suggest that a
      role of G-U base pairs is to allow breathing of the edited mRNA-gRNA hybrid and
      formation of the upstream anchor hybrid.

PMID- 1379520
TI  - Generation of unexpected editing patterns in Leishmania tarentolae mitochondrial
      mRNAs: misediting produced by misguiding.
AB  - We have analyzed the generation of unexpected patterns of RNA editing, i.e.,
      those not following a strict 3' to 5' progression, which occur in junction
      regions between fully edited and preedited sequences. Evidence is presented that
      these patterns are generated by misediting due to specific events of misguiding.
      Misediting can occur through the interaction of inappropriate gRNAs with mRNAs or
      appropriate gRNAs in an incorrect fashion. Four possible mechanisms for the
      generation of misedited sequences are presented. Chimeric molecules have been
      detected in steady-state mitochondrial RNAs that are composed of misguiding gRNAs
      covalently linked to mRNAs at misediting sites by the 3' oligo(U) tail. We
      propose that misediting within junction regions can be corrected by appropriately
      acting gRNAs.

PMID- 1379521
TI  - Chemical modification of recombinant human granulocyte colony-stimulating factor
      by polyethylene glycol increases its biological activity in vivo.
AB  - Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) produced in
      Escherichia coli was chemically modified by polyethylene glycol (PEG) of
      molecular weights 4,500 or 10,000. The neutrophils observed at 32 hours after
      intravenous injection of the rHuG-CSF modified with PEG (4,500) or PEG (10,000)
      to mice were, respectively, 2.5 times and 5 times more than that observed after
      the injection of the unmodified rHuG-CSF. These results show that the covalent
      attachment of PEG to rHuG-CSF enhanced its pharmacological activity in vivo and
      that the modification with the larger PEG molecule is more effective to enhance
      the in vivo activity of rHuG-CSF.

PMID- 1379522
TI  - Neoadjuvant chemotherapy with cisplatin, vincristine, and bleomycin and radical
      surgery in early-stage bulky cervical carcinoma.
AB  - Neoadjuvant chemotherapy consisting of 2-3 courses of cisplatin, vincristine, and
      bleomycin was used in the primary treatment of 36 consecutive patients with
      locally advanced early-stage cervical carcinoma [International Federation of
      Gynecology and Obstetrics (FIGO) stages Ib or IIa; tumor size, greater than or
      equal to 4 cm]. The effectiveness of the preoperative chemotherapy was evaluated
      in the surgical specimens. Among the 33 evaluable patients, the overall clinical
      response rate was 84.8%, which included a complete response in 8 patients (24.2%)
      and a partial response in 20 subjects (60.6%). No residual tumor was found in the
      surgical specimens obtained from 2 complete responders. This therapy induced
      varying degrees of tumor shrinkage and rendered radical surgery feasible in all
      evaluable cases despite the initial bulky size of the lesions. No significant
      difference was observed in the response rate according to age and disease stage.
      Lymph-node metastases were found after chemotherapy in 18.2% (6/33) of the
      patients. Grade II and III hematological toxicities occurred in 23.3% of the 90
      chemotherapy cycles completed. Nausea and vomiting occurred to a mild to moderate
      degree in 75 (83.3%) cycles. These preliminary results suggest that the
      administration of induction chemotherapy involving two to three courses of
      cisplatin, vincristine, and bleomycin prior to surgery is effective in reducing
      the tumor volume and in providing better circumstances for surgical removal of
      the early yet bulky cervical tumors and results in tolerable toxicity. This
      protocol is now undergoing prospective randomized trials to test its impact on
      long-term survival.

PMID- 1379523
TI  - Phase I trial of a 72-h continuous-infusion schedule of fazarabine.
AB  - Fazarabine (Ara-AC), a structural analog derived from the antitumor nucleoside
      cytosine arabanoside (Ara-C) and 5-azacytidine (5-AC), was studied in a phase I
      clinical trial. Doses ranging from 0.2 to 2.0 mg m-2 h-1 were given intravenously
      over 72 h every 28 days. The maximum tolerated dose (MDT) was 2.00 mg m-2 h-1.
      The dose-limiting toxicity was myelosuppression, with granulocytopenia being
      quantitatively more important than thrombocytopenia or anemia. Nonhematologic
      toxicity was minimal. Associated with the solvent dimethylsulfoxide (DMSO) was a
      bitter taste and a garlic-like odor.

PMID- 1379524
TI  - Factors influencing the reaction of alpha 1-fetoprotein with concanavalin A and
      Lens culinaris agglutinin in crossed affinoimmunoelectrophoresis.
AB  - Concanavalin A (Con A) and lentil lectin (LCA) analysis of alpha-fetoprotein
      (AFP) glycosylation heterogeneity is used in a variety of clinical situations. We
      studied the influence of analytical conditions on the separation of AFP
      glycoforms by using lectin-crossed affinoimmunoelectrophoresis, regardless of the
      AFP concentration, which can vary over a wide range in biological fluids. We
      defined the optimal concentration of Con A (2 g/L) and LCA (0.35 g/L) in the
      first-dimension gel, together with the optimum antigen (AFP)/antibody ratio in
      the second-dimension gel. The presence of protein in the diluent used for AFP
      samples was found to change the shape of crossed affinoimmunoelectrophoresis
      patterns without changing the percentage composition of AFP fractions. The within
      run CV was less than 4% for both lectins, and the between-run CV was less than
      6.3%. The minimal quantity of AFP that provided a visible pattern with both
      lectins was 4 ng, corresponding to 50 microL of an 80 micrograms/L AFP sample.
      These technical conditions allow the cellular origin of AFP to be determined,
      regardless of the concentration in the sample. Typical AFP lectin patterns of
      secreting tumors are compared with fetal and cord serum AFP.

PMID- 1379525
TI  - Macroamylases: differences in activity against various-size substrates.
AB  - Hyperamylasemia caused by macroamylases can lead to the overdiagnosis of acute
      pancreatitis. We examined whether interference from macroamylase is less in
      assays that use high-molecular-weight rather than oligosaccharide substrates. We
      hypothesized that high-molecular-weight substrates would be sterically excluded
      from macroamylasemic complexes and thus would be hydrolyzed less efficiently.
      Eighteen macroamylasemic samples were assayed by using red-dyed amylopectin or
      blue-dyed starch as polysaccharide substrates or by using maltoheptaose or
      maltotetraose as oligosaccharide substrates. The oligosaccharide substrates gave
      comparable results (y = 0.81x + 83); we observed consistently lower activities
      for amylopectin than for maltotetraose (y = 0.32x + 38). We observed no bias
      among methods when nonmacroamylasemic specimens were analyzed. The mechanism of
      this difference was examined by adding anti-human pancreatic amylase antibodies
      to hyperamylasemic serum samples from patients without macroamylasemia and
      purified human pancreatic or salivary isoamylases. In each case, polyclonal and
      monoclonal antibodies lowered amylase activity more in assays with complex
      polysaccharides than in those with oligosaccharides. The use of high-molecular
      weight substrates diminishes interference, and detection of suspected
      macroamylasemia may be possible through comparison of activities determined from
      automated methods that use different substrates.

PMID- 1379526
TI  - Hemoglobin A1c by HPLC with the Pharmacia Mono S HR 5/N cation-exchange column:
      influence of sample protein load on optimal chromatographic conditions.
AB  - The Pharmacia Mono S HR 5/5 column has been optimized for hemoglobin A1c analysis
      by HPLC by using a much smaller column load, decreased buffer flow rate, and a
      steeper gradient than was used in previously described methods. Superior
      chromatographic separation, shorter analysis time, and a greatly extended column
      life have resulted.

PMID- 1379527
TI  - Antigenic determinants of the 70-kDa subunit of the Ku autoantigen.
AB  - Autoantibodies against Ku antigen were found in subsets of sera from patients
      with rheumatic diseases. The Ku autoantigen was characterized as a DNA-binding
      protein complex composed of two subunits, 70 and 86 kDa. In this study, we report
      the amino acid sequences of the 70-kDa subunit that are important for
      interactions with a monoclonal and autoimmune antibodies. Full-length cDNA and
      numerous 5' and 3' deletion mutants were expressed in bacteria and the
      immunoreactivity of the fusion proteins was analyzed by Western blotting. The
      reactivity of the monoclonal antibody depended on the region between Ile321 and
      Phe350. Ten autoimmune sera were tested for reactivity with deletion mutants in
      immunoblots. The reactivity of six sera strongly depended on the C-terminal amino
      acids and four sera did not show such dependence; however, these C-terminal
      sequences did not react with the sera when expressed alone. These results
      strongly suggest the conformational nature of the Ku autoepitopes. Interestingly,
      the DNA-binding activity of this Ku protein subunit analyzed by Southwestern blot
      depended on the same C-terminal amino acids that were involved in interactions
      with autoantibodies, indicating that anti-Ku autoantibodies are directed to
      conformationally intact Ku antigen. Reactivities of the autoimmune sera with Met1
      Arg115, Met116-Val149, and Val149-Arg586 were also observed. These results
      demonstrate that different amino acid regions can be involved in interactions
      with autoimmune antibodies.

PMID- 1379528
TI  - Decreased monocyte-mediated angiogenesis in scleroderma.
AB  - Scleroderma is a disease characterized by proliferative vascular lesions in which
      monocytes/macrophages may play a key role. Monocytes were isolated from 14
      scleroderma patients and 11 normal controls and cultured with or without
      lipopolysaccharide (LPS) (5 micrograms/ml). Monocyte-conditioned medium was
      assayed in the rat corneal bioassay for angiogenesis. Conditioned medium from
      normal monocytes was nonangiogenic, as was conditioned medium from scleroderma
      monocytes. While conditioned medium from LPS-activated normal monocytes was
      potently angiogenic in 11/13 corneas, conditioned medium from LPS-activated
      scleroderma monocytes was angiogenic in only 3/14 corneas. Levels of the
      angiogenic cytokine tumor necrosis factor-alpha (TNF-alpha) were measured in
      conditioned medium from scleroderma and normal monocytes. TNF-alpha levels were
      not significantly different in patient and control groups and thus do not account
      for the decreased angiogenic activity exhibited by scleroderma monocytes. As
      monocytes require activation to produce angiogenic activity, we determined the
      cell surface binding of monoclonal antibodies to activation-related (HLA-DR, 3D8,
      and 8D7) and other (Leu-M5) markers on monocytes by radioimmunoassay. Monocytes
      were cultured alone, with LPS (5 micrograms/ml), or with interferon-gamma (IFN)
      (200 units/ml). The usual increase in binding of anti-HLA-DR on stimulation of
      scleroderma monocytes with IFN was slightly less than that of controls. IFN
      stimulated monocytes bound less anti-8D7 than controls. Anti-3D8 and anti-Leu-M5
      binding was comparable in both groups. These results suggest that scleroderma
      monocytes do not produce normal levels of angiogenic activity with LPS
      stimulation, have some altered markers of activation on their cell surfaces, and
      may thus contribute to the aberrant vascular proliferation found in this disease.

PMID- 1379529
TI  - Effects of granulocyte colony-stimulating factor in modifying mortality from
      Pseudomonas aeruginosa pneumonia after hemorrhage.
AB  - BACKGROUND AND METHODS: Alterations in immune function occurring after hemorrhage
      and trauma may contribute to the high occurrence rates of nosocomial pneumonia,
      multiorgan system failure, morbidity, and mortality in this setting. Therapy with
      granulocyte colony-stimulating factor (G-CSF) can increase neutrophil numbers and
      function, and enhance resistance to infection in experimental and clinical
      settings associated with abnormal immune function. To investigate whether
      treatment with G-CSF could increase resistance to pneumonia after hemorrhage, we
      bled mice 30% of the blood volume and treated them with various doses of G-CSF,
      starting either immediately or 2 days after hemorrhage. Pseudomonas aeruginosa
      pneumonia was induced by the intratracheal instillation of 2 x 10(7) colony
      forming units of P. aeruginosa 4 days after blood loss, and mortality was
      assessed over the next 7 days. RESULTS: Treatment of mice with 100 or 500
      micrograms/kg/day G-CSF, but not with 50 micrograms/kg/day, resulted in
      significant increases in the numbers of circulating polymorphonuclear cells.
      Platelet counts significantly decreased in mice given 500 micrograms/kg/day G
      CSF. Mice given 100 micrograms/kg/day G-CSF starting 2 days after blood loss had
      improved outcome compared with vehicle-treated controls (38% survival rate in the
      G-CSF treated group vs. 8% in controls, p less than .05). There also was a trend
      toward an improved survival rate in mice treated with 50 micrograms/kg/day G-CSF
      for 4 days after hemorrhage (46% survival rate in G-CSF treated vs. 17% in
      controls). CONCLUSIONS: G-CSF prophylactically administered after hemorrhage can
      improve survival from pneumonia due to P. aeruginosa. However, the protection
      afforded by G-CSF was highly dependent on the dosing schedule used.

PMID- 1379530
TI  - Hemodynamic, renal, and hormonal actions of aprotinin in an ovine model of septic
      shock.
AB  - BACKGROUND AND METHODS: Previous studies documented activation of protease
      enzymes such as the plasma kallikrein-kinin system in endotoxemia and sepsis,
      both in experimental animals and in patients. We investigated the actions of
      aprotinin (a protease inhibitor that binds to plasma kallikrein) on systemic
      hemodynamics and renal function, in an ovine model of septic shock. Aprotinin was
      infused intravenously in high dosage (1 x 10(6) kallikrein inhibitor units [KIU]
      loading, 200,000 KIU/hr), commencing 30 mins after surgical induction of sepsis
      (cecal ligation and puncture). RESULTS: In the control group (n = 6), there were
      significant decreases with time in BP and systemic vascular resistance, an
      increase in pulmonary artery pressure, reductions in creatinine clearance and
      sodium excretion, and an increase in plasma renin activity. In aprotinin-treated
      animals (n = 6), none of these changes occurred. There were significant between
      group differences (controls vs. treatment) for mean arterial pressure, pulmonary
      artery pressure, and plasma renin activity. CONCLUSIONS: In this large animal
      model of septic shock, which reproduces the important features of clinical
      sepsis, treatment with aprotinin after the initiation of sepsis appears
      beneficial in relation to systemic hemodynamics, renal function, and hormonal
      stimulation, with no evidence of adverse effects.

PMID- 1379531
TI  - Effect of an omental wrap on the healing and vascularity of compromised
      intestinal anastomoses.
AB  - Adult Wistar rats were used to investigate the ability of an omental wrap to
      limit leakage from compromised intestinal anastomoses. Under ketamine anesthesia,
      a section of small bowel was divided and then reanastomosed using a "control"
      anastomosis, a "deficient" anastomosis, or an "ischemic" anastomosis, plus or
      minus the addition of a wrap of omentum. Initially 10 rats were randomly assigned
      to each group. Nineteen of the 20 rats with unwrapped compromised anastomoses
      died within six weeks, compared with five deaths in the rats protected by an
      omental wrap (Fisher's exact test; P less than 0.01). The experiment was then
      repeated with a sample of rats from each anastomotic group being sacrificed for
      histologic examination on days 2 to 7, 10, 14, and 42. At the time of sacrifice a
      dye was injected into the omental vasculature to determine its contribution to
      the healing anastomosis. An anastomosis could be demonstrated between omental and
      bowel wall vessels by the third postoperative day. At one week the infarcted
      bowel edges were being resorbed and the omentum formed a fibrotic cylinder
      aligning the separated ends of bowel wall. At six weeks the scar became more
      contracted and the bowel mucosa had started to grow onto its luminal surface. It
      is concluded from this study that the omental wrap is protective to a compromised
      anastomosis by providing a biologically viable plug to prevent early leakage and
      a source of granulation tissue and neovasculature for later wound repair.

PMID- 1379532
TI  - New antiepileptic drugs: from serendipity to rational discovery.
AB  - Antiepileptic drug discovery has made enormous progress from the serendipity and
      screening processes of earlier days to the rational drug development of today.
      The modern era of research began with the recognition that enhancement of
      inhibitory processes in the brain might favorably influence the propensity for
      seizures, gamma-aminobutyric acid (GABA) being the main inhibitory transmitter.
      Work in this field led to the development of vigabatrin, which inhibits the
      enzyme responsible for the degradation of GABA. More recently, research has
      focused on the therapeutic potential of blocking excitatory amino acids--in
      particular glutamate. Of the three receptors for glutamate, the N-methyl-D
      aspartate (NMDA) receptor is considered the one of most interest in epilepsy, and
      research on a series of competitive NMDA receptor antagonists--especially those
      that are orally active--is in the forefront of antiepileptic drug development
      today. A further alternative for diminishing neuronal excitability is to modulate
      sodium, potassium, or calcium channels. The latter are especially implicated in
      absence seizures.

PMID- 1379533
TI  - Role of nonacidic endosomes in recycling of ADH-sensitive water channel
      structures.
AB  - Toad urinary bladder epithelial cells respond to the hormone ADH by increasing
      the water permeability of their luminal membrane. This action is mediated by
      insertion into the apical membrane of specific water channels. In the absence of
      ADH these channels appear to be present in tubular cytoplasmic vesicles as
      morphologically distinctive intramembrane structures called particle aggregates.
      ADH induces these vesicles to fuse with the apical membrane, transferring their
      aggregate-water channels into the apical membrane. When ADH stimulation is
      removed (ADH reversal), aggregates and fluid-phase markers from the mucosal bath
      appear in water-permeable vesicles in the cytoplasm. We have examined the fate of
      fluid-phase markers and aggregates with time after ADH reversal. Although the
      fluid-phase markers horseradish peroxidase and colloidal gold are initially found
      predominantly in tubular vesicles near the apical surface, by 30 min the markers
      were found in perinuclear multivesicular bodies (MVBs) of heterogeneous size and
      shape. These MVBs appear to be nonacidic since they fail to accumulate DAMP. Acid
      phosphatase (AcPase) was undetectable in these structures. After 60 min, labeled
      MVBs tended to be smaller, and some of these structures displayed DAMP
      accumulation and AcPase activity. By evaluation of uncleaned replicas it was
      possible to localize recycled aggregate-water channels with respect to
      internalized fluid-phase markers. Thirty minutes after retrieval from the apical
      surface in tubular vesicles, aggregates could be localized to both the central
      body and tubular projections of labeled MVBs. At 60 min following reversal, most
      MVBs had a reduced number of aggregates compared with 30 min, and compact
      structures could be identified that contained markers but no detectable
      aggregates. These observations show that aggregates and fluid-phase markers enter
      a nonacidic endosomal compartment with an MVB morphology following ADH reversal.
      At extended times following reversal, labeled MVBS having lysosomal
      characteristics and labeled MVBs having no detectable aggregates can be found,
      suggesting that aggregates are sorted or degraded prior to this stage.

PMID- 1379534
TI  - Morphology of sympathetic preganglionic neurons innervating the superior cervical
      ganglion in the chicken: an immunohistochemical study using retrograde labeling
      of cholera toxin subunit B.
AB  - Preganglionic sympathetic neurons (SPNs) in the chicken were demonstrated
      immunohistochemically using cholera toxin subunit B (CTb) as a retrograde tracer.
      After injection of CTb-solution into the superior cervical ganglion, labeled SPNs
      were mainly found in the ipsilateral sympathetic preganglionic column of Terni
      (the column of Terni), with only a few in the intermediate zone. They were
      observed from the caudal half of the 15th cervical segment to the rostral tip of
      the 3rd thoracic segment. Cell somata of SPNs were loosely packed within the
      column of Terni, where they had an elliptic shape with the long axis oriented
      rostrocaudally. In the horizontal plane three kinds of dendrites could be
      discriminated on the basis of their orientation. Longitudinally oriented
      dendrites emanated from the rostral and the caudal poles of the SPNs. Medially
      oriented dendrites were observed to cross the midline and enter the contralateral
      column of Terni, where they further branched to form a loose dendritic plexus;
      some extended beyond the lateral limit of the contralateral column of Terni to
      reach the intermediate zone. Laterally oriented dendrites formed periodically
      arranged dendritic bundles projecting into the intermediate zone. The present
      findings provide a detailed account of the dendritic organization of SPNs in the
      chicken, and suggest that avian SPNs share certain structural features in common
      with mammalian SPNs.

PMID- 1379535
TI  - Axonal trajectories of single Forel's field H neurones in the mesencephalon, pons
      and medulla oblongata in the cat.
AB  - We studied axonal trajectories of single Forel's field H (FFH) neurones (n = 19)
      in the mesencephalon, pons and medulla by systematic antidromic threshold mapping
      in cats and differentiated them into two major types. Type I neurones were
      characterized by projections to the oculomotor nucleus (IIIn) and type II
      neurones by lack of projections to the IIIn. 2. Type I neurones (11/19) were
      further classified into three subtypes by the lowest level of projections; type
      Ic (n = 3) which projected to the cervical cord and type Ib (n = 7) which
      terminated at the ponto-medullary level and type Ia (n = 1) at more rostral
      level. In the mesencephalon, stem axons passed just lateral to the IIIn and
      projected collaterals to the IIIn and the ventral part of the periaqueductal gray
      matter. In the lower brain stem, stem axons of type Ib and Ic neurones passed in
      the dorsal part of the reticular formation or in the medial longitudinal
      fasciculus and projected collaterals to the dorsal part of the nucleus
      reticularis pontis caudalis (NRPC) and the nucleus reticularis gigantocellularis
      (NRG) and the reticular formation underlying the nucleus prepositus hypoglossi
      (PH) and the raphe region. Projections to the superior colliculus were observed
      in two cases. 3. Type II neurones (8/19) were classified into 2 type IIb
      projecting to the ponto-medullary reticular formation and 6 type IIc projecting
      to the cervical spinal cord. In the mesencephalon, stem axons passed through a
      more lateral region than those of type I and projected collaterals to the
      mesencephalic reticular formation and the red nucleus. In the lower brain stem,
      the stem axons passed in the ventral part of the reticular formation
      corresponding to the central tegmental tract and projected collaterals to the
      ventral part of the NRPC and NRG. Projections to the interstitial nucleus of
      Cajal, the inferior olive and the reticular formation underlying the PH were also
      observed. 4. The dorsal and ventral location of, respectively, stem axons of type
      I and type II neurones in the lower brain stem was confirmed in a larger number
      of neurones in experiments with restricted mapping. 5. There was not much
      difference in location of cell bodies of type I (totally n = 50) and type II (n =
      46) neurones. The proportion of spinal-projecting neurones were larger in type II
      (21/46, 46%) than in type I (7/50, 14%) neurones.

PMID- 1379536
TI  - Prevalence of anti-HCV in subjects of various age groups.
AB  - 812 serum samples from 382 males and 430 females from various age groups were
      examined. All the samples were tested for anti-HCV hepatitis C virus, anti-HBc
      and HBsAg with an enzymeimmunoassay. The total serum prevalence was 2.9% for anti
      HVC, 22.2% for anti-HBc and 4.6% for HBsAg. The seropositivity rates of anti-HCV
      and anti-HBc tended to increase with age, while for HBsAg a more regular pattern
      was observed for the different subject groups. The fact that anti-HCV are more
      frequently found together with HBV markers confirms the existence of similar
      modes of transmission of the two viruses.

PMID- 1379537
TI  - Mechanisms accounting for the impaired natural-killer cell activity in refractory
      anaemia with excess of blasts.
AB  - Natural killer (NK) cells were analyzed in 38 untreated patients with refractory
      anaemia with excess of blasts (RAEB), using cytotoxicity assays and
      immunofluorescence with monoclonal antibodies. We found that patients with RAEB
      have normal numbers of peripheral blood and bone marrow NK cells. NK cells from
      RAEB patients express very low natural-killer cell activity (NKa) which may be
      increased significantly with recombinant alpha-interferon and recombinant
      interleukin-2, although it remains below the lower limit of the control range.
      The cells exhibit normal tumour cell binding capacity, but fail to release
      sufficient amounts of natural-killer cytotoxic factors (NKCFs) upon their
      interaction with NK-sensitive K562 cell targets or their stimulation with
      phytohaemagglutinin. Our results suggest that defective NKa in RAEB patients may
      be due, at least in part, to impaired release of functionally active NKCFs. This
      disturbance is probably the result of some intrinsic defect of RAEB NK cells in
      NKCF production, storage, and/or release. The possibility of an impairment in the
      activation signal provided by the stimulatory K562 cells cannot be excluded,
      although it seems unlikely. We postulate that this abnormality might represent a
      manifestation of dysplastic haemopoiesis. Further studies are certainly needed to
      investigate whether other defective mechanisms are also implicated in the
      determination of the low NKa in patients with RAEB.

PMID- 1379538
TI  - Effect of tandemly repeated AGG triplets on the translation of CAT-mRNA in E.
      coli.
AB  - It has been shown that tandems of rare arginine codons AGG have a strong
      inhibitory effect on translation of mRNA in E. coli [5]. This has been explained
      by the rate-limiting interaction of these codons with the less abundant tRNA(AGG)
      [6]. In this study tandemly repeated AGG triplets were introduced into the
      chloramphenicol acetyltransferase (CAT) gene either upstream of the initiation
      ATG codon or downstream of it (both in frame and out of frame) and the expression
      of the modified genes was investigated. We report that the addition of AGG
      clusters resulted in a substantial inhibitory effect on CAT gene expression
      independently of their localization in mRNA. This inhibitory effect is explained
      by a competition of the tandem AGGAGG with the natural Shine-Dalgarno (SD)
      sequence (consensus AAGGAGGU) for the 3'-end of the 16S small ribosomal RNA
      (rRNA).

PMID- 1379539
TI  - Parathyroid hormone activation of stretch-activated cation channels in
      osteosarcoma cells (UMR-106.01).
AB  - Cell-attached patches of membrane of osteoblast-like cells UMR-106.01 respond to
      bath application of parathyroid hormone (PTH) with an increase in the average
      activity, as well as the single channel conductance, of a stretch-activated non
      selective cation channel. Correlations with whole cell membrane potential and
      conductance changes are considered.

PMID- 1379540
TI  - Molecular cloning of the full-length cDNA encoding the human calbindin-D9k.
AB  - The full-length cDNA encoding the human calbindin-D9k (CaBP-9k) has been cloned
      using reverse transcription/PCR methodology with rat- and bovine-derived primers
      and intestinal RNA. A core product, and both a 5' and 3' product encompassing the
      full-length cDNA were obtained. The clones include coding region for 79 amino
      acids, 57 nucleotides 5'-and 159 nucleotides 3'-non-coding region, and a poly(A)
      tail. The deduced protein sequence is homologous to other mammalian CaBPs.
      Northern analysis revealed the mRNA in human duodenum to be about 600 nucleotides
      in length. Expression levels in adult human tissue were substantially lower than
      in child, rat or porcine intestine.

PMID- 1379541
TI  - Induction of an electrogenic transfer of monovalent cations (K+, NH4+) in
      thylakoid membranes by N,N'-dicyclohexylcarbodiimide.
AB  - The effect of N,N'-dicyclohexylcarbodiimide (DCCD) on photosynthetic electron
      transport and light-induced NH4+ and K+ uptake in the presence of ammonium or
      nigericin was studied. DCCD alone had no effect on either the electron transport
      or the uptake of protons. The simultaneous action of DCCD and low concentrations
      of ammonium or nigericin was shown to lead to a significant increase in the
      electron transport rate and a decrease in the steady-state uptake value of H+ and
      NH4+ or K+. The effect of DCCD on these processes was compared with the effect of
      the ionophore, valinomycin, which transports potassium and ammonium cations
      through membranes. The conclusion was made that 1.0-1.5 mol DCCD per mol
      chlorophyll activated the transfer system of monovalent cations (K+ and NH4+) in
      thylakoid membranes.

PMID- 1379543
TI  - Cell density-dependent expression of heparin-binding growth-associated molecule
      (HB-GAM, p18) and its down-regulation by fibroblast growth factors.
AB  - Heparin-binding growth-associated molecule (HB-GAM) is a developmentally
      regulated protein that is intensely expressed during the rapid postnatal growth
      phase of rat brain. The expression of HB-GAM studied in 12 cell lines was
      restricted to C6 rat glioma cell line and BALB/c 3T3 cells. In BALB/c 3T3 cells
      the expression of HB-GAM was enhanced in confluent and quiescent cell cultures.
      When the confluent cultures were treated with bFGF the expression of HB-GAM mRNA
      was strongly reduced and the protein disappeared rapidly from proliferating
      cells. The data presented suggest involvement of HB-GAM in cell differentiation
      phenomena rather than in cell proliferation.

PMID- 1379542
TI  - Molecular cloning and characterization of human endothelial nitric oxide
      synthase.
AB  - The constitutive calcium/calmodulin-dependent nitric oxide (NO) synthase
      expressed in vascular endothelium shares common biochemical and pharmacologic
      properties with neuronal NO synthase. However, recent cloning and molecular
      characterization of NO synthase from bovine endothelial cells indicated the
      existence of a family of constitutive NO synthases. Accordingly, we undertook
      molecular cloning and sequence analysis of human endothelial NO synthase.
      Complementary DNA clones predict a protein of 1,203 amino acids sharing 94%
      identity with the bovine endothelial protein, but only 60% identity with the rat
      brain NO synthase isoform. Northern blot analysis with an endothelial-derived
      cDNA identified a 4.6-4.8 kb mRNA transcript in HUVEC and in situ hybridization
      localized transcripts to vascular endothelium but not neuronal tissue.

PMID- 1379544
TI  - Unusual effects of benzodiazepines and cyclodiene insecticides on an expressed
      invertebrate GABAA receptor.
AB  - We have previously reported [(1991) EMBO J. 10, 3239-3245] the sequence of an
      invertebrate gamma-aminobutyric acid (GABA) type A (GABAA) receptor polypeptide
      which forms homo-oligomeric GABA-gated, bicuculline-sensitive, chloride-ion
      channels upon heterologous expression. We now demonstrate that the
      benzodiazepines Ro5-4864 (4'-chlorodiazepam) and diazepam, that are active at
      mammalian peripheral benzodiazepine sites, and not those benzodiazepines specific
      for central sites, directly active the homo-oligomeric receptor and evoke larger
      maximal responses than those elicited by GABA. In addition, members of the
      cyclodiene class of insecticides block the channel of the receptor in a manner
      indistinguishable from that of picrotoxin.

PMID- 1379545
TI  - Glycopeptide of P0 protein inhibits homophilic cell adhesion. Competition assay
      with transformants and peptides.
AB  - Expression of major myelin glycoprotein P0 by P0 cDNA transfection into C6 glioma
      cells promoted homophilic cell adhesion of the cells. After the dissociated cells
      were incubated for various times, the number of particles at each time point was
      measured. The total number of particles decreased to 24% in 60 min for
      transformant (C6P0) cells, in contrast to only 68% for control (C6P0') cells. To
      confirm the homophilic mechanism of adhesion, mixed-cell aggregation experiments
      were performed. Among the four synthetic peptides corresponding to a part of the
      P0 sequence used, only peptide 3 (residues 90-96), which contained a carbohydrate
      attaching site, caused considerable inhibition of cell aggregation (approximately
      50%). In addition, the glycopeptide (residues 91-95) obtained from bovine P0
      markedly inhibited cell aggregation (by approximately 85%).

PMID- 1379546
TI  - Insulin-like growth factor II stimulates glucose transport in human skeletal
      muscle.
AB  - We investigated the effect of insulin-like growth factor II (IGF-II) and insulin
      like growth factor binding protein-1 (IGFBP-1) on 3-O-methylglucose transport in
      incubated human skeletal muscle strips. Increasing physiological concentrations
      of IGF-II stimulated glucose transport in a dose-dependent manner. Glucose
      transport was maximally stimulated in the presence of 100 ng/ml (13.4 nM) of IGF
      II, which corresponded to the effect obtained by 100 microU/ml (0.6 nM) of
      insulin. Exposure of muscle strips to IGFBP-1 (500 ng/ml) inhibited the maximal
      effect of IGF-II on glucose transport by 40%. Thus, it is conceivable that IGF-II
      and IGFBP-1 are physiological regulators of the glucose transport process in
      human skeletal muscle.

PMID- 1379547
TI  - Monitor peptide gene expression is increased by exogenous CCK in the rat pancreas
      and in a rat pancreatic acinar cell line (AR4-2J).
AB  - Monitor peptide (CCK-releasing peptide) mRNA increased on the administration of
      CCK in rat pancreas and the AR4-2J pancreatic cell line. Subcutaneous injection
      of CCK into rats at 8 h intervals increased the level of monitor peptide mRNA in
      the pancreas. Concomitant injection of CCK antagonist CR-1409 strongly decreased
      it. The monitor peptide mRNA was also increased by CCK in AR4-2J cells and was
      decreased by the antagonist. These findings suggest that the plasma CCK induced
      by prolonged intake of a high protein diet may be responsible for the adaptative
      increase in the monitor peptide as well as exocrine proteases in the pancreas.

PMID- 1379548
TI  - Class II tubulin, the major brain beta tubulin isotype is polyglutamylated on
      glutamic acid residue 435.
AB  - Protein sequencing shows that porcine brain tubulin retains the N-terminal
      sequences of alpha and beta tubulin after a mild treatment with subtilisin. C
      terminal peptides released by subtilisin were purified and characterized by
      automated Edman degradation and mass spectrometry. We confirm the
      polyglutamylation of alpha tubulin on glutamic acid residue 445 reported by
      others and show in addition that class II beta tubulin, the major beta tubulin
      isotype of adult brain, is also polyglutamylated. The substitution is restricted
      to glutamic acid residue 435. Thus all major tubulin isotypes of adult brain are
      subjected to polyglutamylation.

PMID- 1379549
TI  - Induction of Ca2+/calmodulin-dependent NO synthase in various organs of rats by
      Propionibacterium acnes and lipopolysaccharide treatment.
AB  - Ca2+/calmodulin-dependent nitric oxide synthase was found to be induced during
      rat liver necrosis caused by administration of Propionibacterium acnes and E.
      coli lipopolysaccharide to rats. Examination of the specific induction of
      Ca2+/calmodulin-dependent NO synthase showed that the enzyme was induced in the
      lung, spleen and colon as well as the liver. Northern blot analysis revealed that
      the induction occurred at the transcriptional level.

PMID- 1379550
TI  - Bleomycin-reactive iron in patients with acute non-lymphocytic leukemia.
AB  - Bleomycin-reactive iron was detected in the sera of six out of nine adults
      undergoing intensive chemotherapy for acute non-lymphocytic leukemia. In these
      individuals the corresponding transferrin saturation ranged from 96% to 113% and
      the serum ferritin from 775 to 9975 micrograms/l. Nontransferrin-bound iron has
      been postulated to be a factor in organ toxicity in iron overload conditions such
      as beta thalassemia and hereditary hemochromatosis by facilitating the production
      of tissue-damaging free radicals. We propose that bleomycin-reactive iron should
      be considered as a possible factor in organ dysfunction seen with intensive
      cancer chemotherapy.

PMID- 1379551
TI  - Alpha 2-macroglobulin and other proteinase inhibitors do not interfere with the
      secretion of amyloid precursor protein in mouse neuroblastoma cells.
AB  - A series of proteinase inhibitors active against proteinases of all four major
      classes, including highly purified and well-characterized alpha 2-macroglobulin,
      added to the cell culture medium of murine Neuro 2a neuroblastoma cells did not
      interfere with APP secretase activity. We therefore advance the hypothesis that
      APP secretase activity is localized in an intracellular compartment.

PMID- 1379552
TI  - Molecular cloning and characterization of a novel calcium channel from rabbit
      brain.
AB  - The complete amino acid sequence of a novel calcium channel (designated BII) from
      rabbit brain has been deduced by cloning and sequencing the cDNA. The BII calcium
      channel is structurally more closely related to the BI calcium channel than to
      the cardiac and skeletal muscle L-type calcium channels. Blot hybridization
      analysis of RNA from different tissues and from different regions of the brain
      shows that the BII calcium channel is distributed predominantly in the brain,
      being abundant in the cerebral cortex, hippocampus and corpus striatum.

PMID- 1379553
TI  - Subunit interactions of the Go protein.
AB  - The monoclonal antibody, MONO, recognizes an epitope on the G protein alpha o
      subunit [van der Voorn et al., submitted] and readily immunoprecipitates
      heterotrimeric Go proteins from solubilized, crude bovine brain membranes, as
      well as from a purified bovine brain G protein preparation. Upon incubation of
      the immunoprecipitates with GTP gamma S, all beta gamma-subunits are released
      from the alpha o-subunit. Thus, binding of MONO to the Go protein does not appear
      to interfere with release of bound GDP, binding of GTP gamma S or GTP gamma S
      induced subunit dissociation. However, we have been unable to induce a similar
      dissociation of Go using its physiological activator, GTP. Surprisingly, we did
      not observe any dissociation of Go (bound to MONO) upon dilution in a range from
      500 to 5 nM. Since an apparent Kd of alpha o-GDP for binding beta gamma of 340
      390 nM has been reported [(1989) J. Biol. Chem. 264, 20688-20696] our results
      would suggest that binding of MONO to the alpha o-subunit induces an increased
      affinity of alpha o-GDP for beta gamma. Alternatively, these results could be
      explained if, under the conditions used, the Kd of alpha o-GDP for beta gamma
      were at least two orders of magnitude lower than estimated previously.

PMID- 1379554
TI  - Single channel recording in the chloroplast envelope.
AB  - The patch-clamp technique was applied to study ion channels in the intact
      chloroplast envelope. Three channel types were characterized: two cation
      selective, with a conductance (in 100 mM KCl) of 517 and 1016 pS, respectively,
      and one anion-selective with a conductance of 159 pS. All three channels showed
      voltage-dependent closures at both positive and negative membrane potentials.

PMID- 1379555
TI  - Zinc-induced tyrosine phosphorylation of hippocampal p60c-src is catalyzed by
      another protein tyrosine kinase.
AB  - Tyrosine phosphorylation of p60c-src induced by Zn2+ in rat hippocampal membranes
      is shown to inhibit Src tyrosine kinase activity. Zn2+ catalyzes the
      phosphorylation of p60c-src in the membranes but does not activate
      autophosphorylation of p60c-src immunoprecipitated with anti-Src monoclonal
      antibody. Moreover, the immunoprecipitated Src kinase has no Zn(2+)-induced
      activity in phosphorylation of exogenous substrate, enolase. Cyanogen bromide
      cleavage of p60c-src phosphorylated in the presence of Zn2+ yields a 4-kDa
      phosphopeptide corresponding to phosphorylation of a carboxy-terminal tyrosine
      residue of Src kinase. In conclusion, hippocampal membranes contain a Zn(2+)
      stimulated protein tyrosine kinase capable of regulating the p60c-src activity.

PMID- 1379556
TI  - Elevated cytosolic concentrations of SecA compensate for a protein translocation
      defect in Escherichia coli cells with reduced levels of negatively charged
      phospholipids.
AB  - Cellular extracts from cells with reduced synthesis of negatively charged
      phospholipids were found to support in vitro translocation of the precursor of
      the outer membrane protein PhoE with increased efficiency. Analysis of these
      extracts revealed that they contain increased levels of SecA. SecA depletion
      resulted in a loss of the translocation stimulatory activity, which could be
      restored by re-addition of purified SecA. We conclude that elevated cytosolic
      levels of SecA counteract the reduction of translocation efficiency due to low
      levels of negatively charged phospholipids in the inner membrane.

PMID- 1379557
TI  - Effects of fluorodeoxyuridine and nalidixic acid on the activity of topoisomerase
      I in plasmodia of Physarum polycephalum.
AB  - 1. A regulatory coupling between the rate of cellular transcription and the
      activity of topoisomerase I was investigated in plasmodia of Physarum
      polycephalum treated with fluorodeoxyuridine or nalidixic acid. 2.
      Fluorodeoxyuridine at concentrations above 40 micrograms/ml lowered both the
      incorporation of [3H]uridine and the activity of topoisomerase I to 10% of
      corresponding control values. 3. Nalidixic acid, in the range of concentrations
      between 20-50 micrograms/ml did not inhibit the incorporation of [3H]uridine but
      lowered the activity of topoisomerase I by about half. 4. It is suggested that a
      coupling between the level of transcription and the activity of topoisomerase I
      in Physarum plasmodia involves only about a half of the topoisomerase I activity
      and is limited to transcription occurring on ribosomal genes.

PMID- 1379558
TI  - Epithelial morphogenesis in developing Artemia: the role of cell replication,
      cell shape change, and the cytoskeleton.
AB  - The roles of cell replication and shape change as morphogenetic forces in
      epithelial invagination were examined in instar II Artemia. The epidermal cells
      underwent a fixed pattern of cell division during the first 5 hr of instar II.
      Greater cell replication in the thoracopod bud (ThB) than in the arthrodial
      membrane (AM) region resulted in a higher density of epidermal cells in the ThB
      region (differential cell density). The ratio of cell density (AM/ThB) declined
      from 1.0 to less than 0.80 by Hour 2 of instar II. Invagination of the AM
      occurred during Hour 4 when the AM/ThB reached 0.75. A 2-hr pulse with 5'
      fluorodeoxyuridine (FudR) during instar I delayed completion of the cell
      replication pattern and development of transverse cell files in the ThB region
      for a period equal to the length of the exposure. The delay in the cell division
      program resulted in a cell density ratio of 0.93 at Hour 4, a value normally
      observed in Hour 2 larvae, and evagination of the epidermis did not occur at
      apolysis (Hour 4). The FudR treatment did not perturb the cytoskeleton or the
      initial steps in cell shape change and the larvae formed small segments during
      instar III. Cell shape change within the AM began during Hour 4 as this region
      became significantly thinner than the neighboring ThB region (thickness ratio,
      AM/ThB = 0.77). Before apolysis the AM cells became wedge shaped, a change which
      occurred when the basal region of the cell enlarged. The microtubules and
      microfilaments were reorganized from the apical cytoplasm to the lateral border
      of apposing AM cells. Following apolysis (Late Hour 4) shape change was completed
      as the cells attained a thin spindle form, with microtubule- and microfilament
      rich filopodial extensions which overlapped adjacent AM cells. As contact with
      ThB cells shifted from lateral to apicolateral, the AM cells formed the innermost
      edge of the invagination. Microtubules in the differentiating AM cells contained
      tyrosinated, detyrosinated, and acetylated alpha-tubulin isoforms. Treatment with
      nocodazole, colchicine, taxol, or cytochalasin B blocked AM cell shape change and
      inhibited segmentation, but did not affect the mitotic pattern or differential
      cell density. We conclude that the specific pattern of cell division led to
      differential cell density which, along with AM cell shape change, established the
      conditions necessary to achieve epidermal evagination.

PMID- 1379559
TI  - Activation of voltage-dependent calcium channels of mammalian sperm is required
      for zona pellucida-induced acrosomal exocytosis.
AB  - Previous work indicates that antagonists of the L-type voltage-dependent Ca2+
      channel (VDCC) prevent the Ca(i) increase in mammalian sperm that is promoted by
      incubation in alkaline, K(+)-based media. Here, were provide additional evidence
      that sperm possess VDCC and show that their activation is required for the Ca2+
      entry that mediates acrosomal exocytosis in both the presence and the absence of
      egg agonists. Specifically, we report that: (1) Sperm membrane potential changes,
      Ca(i) elevation, and acrosomal exocytosis have similar K+ dose dependencies,
      consistent with a characteristic requirement of a large depolarization for
      activation of the sperm VDCC; (2) High affinity binding sites (Kd approximately
      0.35 +/- 0.03 and 0.45 +/- 0.06 nM; Bmax = 16.0 +/- 1.4 and 5.8 +/- 0.8 fmole/mg
      protein) for the VDCC antagonist, PN200-110, respectively, are present in
      membrane preparations from sperm of the ram and bull; (3) PN200-110 and the other
      VDCC antagonists nitrendipine, nisoldipine, verapamil, diltiazem, Ni2+, or Co2+
      inhibit (IC50 = 0.1, 0.4, 0.6, 0.8, 1.0, 60, and 110 microM, respectively) the
      acrosomal exocytosis produced by combined elevation of pH0 and membrane
      depolarization; (4) Exocytosis induced by the ZP3 agonist of the mammalian egg
      also is inhibited by VDCC antagonists with similar dose dependencies; (5)
      Depolarizing treatments that presumably activate the sperm VDCC bypass the
      blockade of ZP3-induced exocytosis imposed by pertussis toxin. These results
      indicate that activation of the sperm VDCC is sufficient to induce sperm
      acrosomal exocytosis and that VDCC activation is necessary in the ZP3 signal
      transduction pathway. They also indicate that the presumed G-protein targets of
      pertussis toxin probably produce a required but indirect activation of the
      putative sperm VDCC. Possible intervening events include alteration of the
      voltage sensitivity of the VDCC, membrane depolarization, or both. We suggest
      that the depolarization-induced acrosome reaction may provide a useful system to
      investigate subsequent events in the exocytotic process.

PMID- 1379560
TI  - Effects of acidic and basic fibroblast growth factors (aFGF, bFGF) on glial
      precursor cell proliferation: age dependency and brain region specificity.
AB  - Acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF)
      are present in high levels in most areas of the embryonic rodent brain. To begin
      to understand the role of these growth factors in brain development, the effects
      of aFGF and bFGF on dissociated cell cultures prepared from embryonic and
      neonatal rat brain were studied. Addition of aFGF and heparin or bFGF alone to
      serum-free cultures of the dissociated Embryonic Day (E) 14.5 mesencephalon
      stimulates cell proliferation, as judged by [3H]thymidine autoradiography,
      leading to a maximal 75-fold increase in the total number of cells. This effect
      is dose-dependent with half-maximal increases at concentrations of about 5-6
      ng/ml of aFGF or bFGF and is inhibited by the FGF antagonist HBGF-1U. The effect
      of aFGF on cell proliferation in cultures prepared from E14.5 mesencephalon is
      similar to that in cultures prepared from E14.5 cortex. However, in cultures
      prepared from E14.5 rhombencephalon or diencephalon, the proliferative effect of
      aFGF is much reduced. In all brain areas studied, the proliferative effect of
      aFGF declines with increasing age. Immunocytochemical analysis of E14.5
      mesencephalic cultures demonstrated that the aFGF-induced increase in cell number
      is due to the proliferation of A2B5-immunoreactive (IR) glial precursor cells,
      but not of neuronal precursors, fibroblasts, or microglial cells. Moreover,
      differentiated glial fibrillary acidic protein-IR astrocytes and 2',3'-cyclic
      nucleotide 3'-phosphohydrolase-IR oligodendrocytes were not observed in cultures
      continuously treated with aFGF or bFGF, but were observed in high numbers after
      removal of the growth factors. These results suggest (1) that aFGF and bFGF are
      potent mitogens for glial precursor cells in all embryonic brain regions, (2)
      that the magnitude of the effects of aFGF depends on embryonic age and brain
      region, and (3) that both growth factors inhibit the differentiation of astrocyte
      or oligodendrocyte precursors. These observations made in vitro strongly support
      the hypothesis that FGF plays a critical role in gliogenesis and the timing of
      glial differentiation in the brain.

PMID- 1379562
TI  - A tyrosyl-tRNA synthetase binds specifically to the group I intron catalytic
      core.
AB  - The Neurospora CYT-18 protein, the mitochondrial tyrosyl-tRNA synthetase,
      functions in splicing group I introns in mitochondria. Here, we show that CYT-18
      binds strongly to diverse group I introns that have minimal sequence homology and
      recognizes highly conserved structural features of the catalytic core of these
      introns. Inhibition experiments indicate that the intron RNA and tRNA(Tyr)
      compete for the same or overlapping binding sites in the CYT-18 protein.
      Considered together with functional analysis, our results indicate that the CYT
      18 protein promotes splicing by binding to the intron core and stabilizing it in
      a conformation required for catalytic activity. Furthermore, the specific binding
      of the synthetase suggests that the group I intron catalytic core has structural
      similarities to tRNAs, which could reflect either convergent evolution or an
      evolutionary relationship between group I introns and tRNAs.

PMID- 1379561
TI  - Ca(2+)-activated K+ channels from an insulin-secreting cell line incorporated
      into planar lipid bilayers.
AB  - This study evaluates the use of the planar lipid bilayer as a functional assay of
      Ca(2+)-activated K+ channel activity for use in purification of the channel
      protein. Ca(2+)-activated K+ channels from the plasma membrane of an insulin
      secreting hamster Beta-cell line (HIT T15) were incorporated into planar lipid
      bilayers. The single channel conductance was 233 picoSiemens (pS) in symmetrical
      140 mmol/l KCl and the channel was strongly K(+)-selective (PCl/PK = 0.046;
      PNa/PK = 0.027). Channels incorporated into the bilayer with two orientations. In
      65% of cases, the probability of the channel being open was increased by raising
      calcium on the cis side of the bilayer (to which the membrane vesicles were
      added) or by making the cis side potential more positive. At a membrane potential
      of + 20 mV, which is close to the peak of the Beta-cell action potential, channel
      activity was half-maximal at a Ca2+ concentration of about 15 mumol/l.
      Charybdotoxin greatly reduced the probability of the channel being open when
      added to the side opposite to that at which Ca2+ activated the channel. These
      results resemble those found for Ca(2+)-activated K+ channels in native Beta cell
      membranes and indicate that the channel properties are not significantly altered
      by incorporation in a planar lipid bilayer.

PMID- 1379563
TI  - Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven
      TNF alpha transgenic mice.
AB  - Tumor necrosis factor alpha (TNF alpha) orchestrates a wide range of effects that
      combat severe infections in animals. At lower levels, TNF alpha plays an
      important protective role in stimulating chemotaxis and antimicrobial activity of
      neutrophils, macrophages, and eosinophils. During chronic illness, TNF alpha
      secretion can be elevated markedly, giving rise to cachexia, hemorrhage, necrosis
      and, ultimately, death. Although TNF alpha may mediate many of its effects
      through macrophages, 30% of TNF alpha injected into animals concentrates in the
      skin. In recent years, it has been shown that keratinocytes can be induced to
      synthesize TNF alpha. To explore the role of TNF alpha synthesis in
      keratinocytes, we used a keratin-14 (K14) promoter to target human TNF alpha
      expression in the epidermis and other stratified squamous epithelia of transgenic
      mice. Most mice expressing the K14-TNF alpha transgene stopped gaining weight
      within 1 week postbirth, and exhibited retarded hair growth. In the skin, adipose
      production was profoundly inhibited, whereas signs of fibrosis and immune
      infiltration were evident in the dermis. Over time, the epidermis exhibited an
      increased stratum corneum, as signs of necrosis began to appear in the skin.
      Within 3-5 weeks, the mice displayed features characteristic of cachexia and
      necrosis. Our results suggest that TNF alpha expression by keratinocytes not only
      plays a role in inflammatory and graft-versus-host-disease-like responses in the
      skin, but also in other tissues, apparently by virtue of stratified squamous
      epithelial-derived TNF alpha entering the bloodstream. Our results have enabled
      the first evaluation of many of the effects of TNF alpha in transgenic animals.

PMID- 1379564
TI  - Endogenous retroviral sequences are required for tissue-specific expression of a
      human salivary amylase gene.
AB  - The human salivary amylase genes are associated with two inserted elements, a
      gamma-actin-processed pseudogene and an endogenous retroviral-like element. To
      test the contribution of these inserted elements to tissue specificity, 25 lines
      of transgenic mice carrying 10 amylase constructs were established. A 1-kb
      fragment of AMY1C (-1003 to +2) was found to be sufficient for parotid-specific
      expression of a human growth hormone reporter gene. The 1-kb fragment is entirely
      derived from inserted sequences. Deletion from -1003 to -826 resulted in reduced
      levels of transgene expression and loss of tissue specificity. The fragment -1003
      to -327 was sufficient to transfer parotid specificity to the thymidine kinase
      promoter. The data demonstrate that the functional tissue-specific promoter of
      human AMY1C is derived from inserted sequences and that parotid expression can be
      conferred by sequences derived solely from the retrovirus. A role for
      retrotransposition in the evolution of gene regulation is indicated by these and
      other recent observations.

PMID- 1379565
TI  - The Mycobacterium tuberculosis 38-kDa antigen: overproduction in Escherichia
      coli, purification and characterization.
AB  - The 38-kDa protein (Ag38) of the Gram+ bacterium, Mycobacterium tuberculosis
      H37Rv, is an immunodominant antigen of potential utility for diagnosis and
      vaccine development. Assessment of this potential requires large amounts of the
      purified protein that would be difficult, if not impossible, to obtain from M.
      tuberculosis itself. The gene coding for Ag38 had been previously cloned and in
      the present study was expressed as an unfused protein in Escherichia coli under
      the control of strong transcriptional (bacteriophage lambda pLpR) and
      translational (atpE) signals. Fermentation of the recombinant E. coli K-12 strain
      CAG629[pMS9-2], which is deficient in Lon protease and the heat-shock response,
      produced recombinant Ag38 (reAg38) at high levels (about 10% of total cellular
      protein). The reAg38, which accumulated as inclusion bodies, was completely
      solubilized in 6 M guanidine.HCl, refolded and purified to apparent homogeneity.
      The product showed the expected amino acid composition and M(r), and had similar
      reactivities as the native protein with three different mAb. Polyclonal
      antibodies raised against reAg38 reacted strongly with the native antigen in
      enzyme-linked immunosorbent assay. These results demonstrate that reAg38, which
      cannot be distinguished antigenically from the native protein of M. tuberculosis,
      can be prepared in quantity from E. coli.

PMID- 1379566
TI  - Sequences encoding the protein and RNA components of ribonuclease P from
      Streptomyces bikiniensis var. zorbonensis.
AB  - The genes encoding the RNA (rnpB) and protein (rnpA) subunits of ribonuclease P
      (RNase P) of Streptomyces bikiniensis var. zorbonensis have been cloned by
      complementing the temperature-sensitive growth phenotype of Escherichia coli
      strains that carry mutations in these genes. The rnpB sequence of S. bikiniensis
      includes new covariations that lead to refinement of the previous secondary
      structure models for RNase P RNAs. The deduced amino acid sequence of S.
      bikiniensis RNase P is conserved with that of other known RNase P proteins only
      to a limited extent. Immediately upstream from rnpA is an open reading frame that
      codes for the highly conserved ribosomal protein, L34. This same gene arrangement
      occurs in all bacteria studied to date.

PMID- 1379567
TI  - Evidence against an autoimmune aetiology for inflammatory bowel diseases.

PMID- 1379570
TI  - [Surgical therapy of congenital cardiovascular abnormalities. Palliation,
      correction, transplantation].
AB  - Thanks to new and further developments of surgical procedures, it has now become
      possible to provide surgical treatment for any form of congenital heart defect.
      For some procedures, however, long-term results are not yet available. In this
      review, currently accepted basic principles of modern surgical treatment of
      congenital heart disease are discussed. On the basis of the most common
      anomalies, the various surgical techniques (palliation, correction and heart
      transplantation) are considered.

PMID- 1379569
TI  - Relation of diagnostic serum amylase levels to aetiology and severity of acute
      pancreatitis.
AB  - The sensitivity of diagnostic serum amylase (greater than 1000 iu/l) was assessed
      in 417 patients with acute pancreatitis as a result of gall stones (258), alcohol
      (104), or miscellaneous causes (55), of whom 111 (27%) had a clinically severe
      attack (including 34 deaths). On hospital admission, an amylase value diagnostic
      of pancreatitis was found in 96.1% of all mild cases and in 87.4% of severe cases
      (p less than 0.001); at 48 hours these values were 33.3% and 48.2% respectively
      (p = 0.026). Diagnostic amylase levels for alcoholic patients were found in 86%
      of mild cases on admission and in 76% of severe cases (p less than 0.001,
      compared with other groups). The diagnostic levels were also significantly lower
      at 24 hours for both the alcoholic and miscellaneous groups compared with the
      gall stone group (p less than 0.001). Eight of 27 (30%) patients with a serum
      amylase activity less than 1000 iu/l had pancreatic necrosis compared with 12 of
      the remaining 390 (3.1%) patients (p less than 0.001); the mortality was also
      significantly different (44% v 5.6% respectively, p less than 0.001). These data
      support the view that more sensitive tests for acute pancreatitis are needed for
      routine use especially in those whose disease has an alcoholic aetiology.

PMID- 1379568
TI  - Surface epithelium related activation of complement differs in Crohn's disease
      and ulcerative colitis.
AB  - IgG1 and activated complement are colocalised on the colonic epithelial brush
      border in active ulcerative colitis. To investigate whether such deposition is
      specific for ulcerative colitis, we examined ethanol fixed mucosal specimens from
      18 patients with Crohn's colitis and 14 with terminal ileitis by indirect two
      colour immunofluorescence staining. Monoclonal antibodies to the IgG subclasses
      and to neoepitopes of activated complement C3b and the terminal complement
      complex were used in combination with rabbit antiserum to C1q, C4c or
      cytokeratin. Granular deposition of C3b and terminal complement complex were
      observed at the luminal face of the surface epithelium in 10 of 18 patients with
      Crohn's colitis. Specimens from eight of 14 patients with ileal involvement were
      intensely stained for activated complement (primarily C3b) within the surface
      mucus layer. No epithelial IgG, C1q or C4c deposition was observed. The results
      suggest that early and late phase complement activation takes place at the
      luminal face of the epithelium in Crohn's disease. The absence of colocalised IgG
      and complement components involved in the classical activation pathway (C1q and
      C4c), however, suggest that other immunopathological mechanisms (the alternative
      pathway?) are primarily involved in Crohn's disease in contrast with ulcerative
      colitis.

PMID- 1379572
TI  - Deep juvenile xanthogranuloma: a lesion related to dermal indeterminate cells.
AB  - Juvenile xanthogranuloma (JXG) is considered to represent a lesion originating
      from histiocytes. Three cases of deeply located JXG and one case of cutaneous JXG
      were studied. One case with extensive mesenteric involvement presented with
      hypercalcemia and one case with liver involvement had hypergammaglobulinemia.
      Immunohistochemistry, electron microscopy, karyotyping, and DNA flow cytometry
      were used to determine the phenotype of the cells involved and to find further
      clues as to the histogenesis of these lesions. Immunohistochemically, all lesions
      studied expressed the CD1a antigen but showed no labeling for S-100 protein. The
      cells did not contain Birbeck granules. From these data it is suggested that the
      cells involved are of indeterminate dermal histiocyte lineage and that occurrence
      of deep located lesions of JXG may be due to migration of CD1 a-positive
      histiocytes.

PMID- 1379571
TI  - Malignant peripheral nerve sheath tumors: an immunohistochemical study in
      relation to ultrastructural features.
AB  - The constituent cells in malignant peripheral nerve sheath tumors were examined
      by studying the expression of immunohistochemical markers for Schwann cells and
      perineurial cells in relation to ultrastructural features in 12 malignant
      peripheral nerve sheath tumors. Ultrastructural studies demonstrated mixed
      proliferation of Schwann cells, perineurial cells, fibroblastic cells, and
      primitive cells in many malignant peripheral nerve sheath tumors. Expression of S
      100 protein was well correlated with Schwann cell-like differentiation of tumor
      cells. However, Leu-7 and epithelial membrane antigen, which have been considered
      to be specific to Schwann cells and perineurial cells, respectively, were common
      to Schwann cells, perineurial cells, and primitive cells. The common
      immunophenotypic expression suggests a close relationship among these cell types.
      The unusual expression of cytokeratin could be explained by the plasticity of
      intermediate filament expression.

PMID- 1379573
TI  - Mucin histochemistry of pancreatic duct cell carcinoma, with special reference to
      organoid differentiation simulating gastric pyloric mucosa.
AB  - The present study was undertaken to explore mucins produced in normal,
      metaplastic, and hyperplastic ductal epithelia as well as in carcinoma tissues of
      the pancreas, and used a battery of histochemical techniques. Thirty-five cases
      of ordinary pancreatic duct cell carcinoma and nine cases of duct cell carcinoma,
      which fulfilled the clinical criteria of "mucin-producing carcinoma of the
      pancreas," were examined. The results indicated that all lesions of mucinous
      metaplasia with or without papillary hyperplasia as well as atypical hyperplasia
      characteristically had gastric mucins and showed organoid differentiation
      simulating the gastric pyloric mucosa, but never stained for 8-O-acetyl-N
      acetylneuraminic acid, which is a histochemical marker of the large intestine.
      Ordinary duct cell carcinoma also contained gastric mucins and small intestinal
      mucins and showed organoid differentiation, but rarely had 8-O-acetyl-N
      acetylneuraminic acid. Mucin-producing carcinomas were classified into two
      groups: the ordinary duct cell carcinoma group and a group that showed marked
      atrophy and extensive fibrosis of the parenchyma, a lack of organoid
      differentiation and gastric mucins, and an abundance of large and small
      intestinal mucins. These results suggest that gastrointestinal mucins are useful
      markers to detect cancer-related lesions and cancers of the pancreas.

PMID- 1379574
TI  - Precursors of pyrimidine nucleotide biosynthesis for gravid Angiostrongylus
      cantonensis (Nematoda: Metastrongyloidea).
AB  - Gravid Angiostrongylus cantonensis can utilize radiolabelled bicarbonate,
      orotate, uracil, uridine and cytidine but not cytosine, thymine and thymidine for
      the synthesis of RNA and DNA. In cell-free extracts of the worm, a
      phosphoribosyltransferase was shown to convert orotate to OMP and uracil to UMP.
      A similar reaction was not observed with cytosine and thymine. Uridine was
      readily phosphorylated by a kinase but a similar reaction for thymidine and
      deoxyuridine was not found. Cytidine could be phosphorylated by a kinase or be
      deaminated by a deaminase to uridine. No deaminase for cytosine was detected.
      There was also no phosphotransferase activity for pyrimidine nucleosides in the
      cytosolic or membrane fractions. Pyrimidine nucleosides were, in general,
      converted to the bases by a phosphorylase reaction but only uracil and thymine
      could form nucleosides in the reverse reaction. The activity of thymidylate
      synthetase was also measured. These results indicate that the nematode
      synthesizes pyrimidine nucleotides by de novo synthesis and by utilization of
      uridine and uracil and that cytosine and thymine nucleotides are formed mainly
      through UMP. The thymidylate synthetase reaction appears to be vital for the
      growth of the parasite.

PMID- 1379576
TI  - [Prevention of thromboembolism in hip traumatology: low molecular weight heparin
      versus dextran].
AB  - A prospective, randomized trial has been undertaken to evaluate the prophylactic
      effects of low molecular weight heparin (LMWH) and dextran-70 in 216 patients
      with hip fracture during a postoperative period of ten days. Deep vein thrombosis
      (DVT) was diagnosed using the 125Iodine fibrinogen uptake test, confirmed by
      ascending venography. 113 patients received LMWH and 103 dextran-70. The
      frequency of DTV of 14.2% in the LMWH group was significantly lower compared with
      the 30.1% in the dextran group (p less than 0.003). During the first 10 days
      postoperative there were no fatal pulmonary embolism (PE). After this period PE
      occurred in 2 patients (1.8%) in the LMWH group and 1 patient (1.0%) in the
      dextran group. In each group one patient died from PE. There was no major
      bleeding in either group. The frequency of local complications was slightly
      higher in the dextran group (10.7%) compared with the LMWH group (3.5%). The
      postoperative hemoglobin level was significantly lower in dextran treated
      patients than in patients receiving LMWH (p less than 0.0001).

PMID- 1379575
TI  - Hepatic resection for 28 patients with small hepatocellular carcinoma.
AB  - Twenty-eight patients with hepatocellular carcinoma (HCC) of not larger than 5 cm
      diameter were surgically treated during the 12 years from 1977 to 1988, twenty
      five of them since 1983. Half of the patients were admitted for check up because
      of elevated serum AFP and were high risk subjects. Serum HBsAg were positive in
      24 (85.7%). Serum AFP was less than 10 ng/ml in 2 (7.1%) and greater than or
      equal to 200 ng/ml in 14 (50%). Coexistent liver cirrhosis was found in 21 (75%).
      Local resection or partial hepatectomy played a major surgical role in small HCC,
      especially in the presence of cirrhosis and tumor in right liver. The cumulative
      survival rates for the 28 patients treated by hepatic resection at 1, 2 and 5
      years were 60.6, 42.5 and 42.5 percent. The survival rate of patients with tumor
      size not larger than 3 cm diameter is not better than those with tumor size
      between 3 cm and 5 cm. The small HCC patients with AFP less than or equal to 200
      ng/ml had better survival than those with AFP greater than 200 ng/ml.

PMID- 1379577
TI  - Inhibition of heat inactivation of reverse transcriptase of human
      immunodeficiency virus type 1 by seropositive sera.
AB  - The reverse transcriptase (RT) activity of a lysate of human immunodeficiency
      virus type 1 (HIV) was almost completely inactivated by incubation at 56 degrees
      C for 20-30 min. The heat-inactivation of RT in the virus lysate or purified RT
      was partially inhibited in the presence of some human sera or plasma containing
      antibodies against HIV. The IgG fraction purified from the seropositive sera was
      responsible for stabilization of RT upon heat inactivation. This is a new assay
      system for detection of antibodies against RT.

PMID- 1379578
TI  - Enhancing effect of pokeweed mitogen on the proliferation and the cytotoxicity of
      lymphokine-activated killer cells.
AB  - In order to obtain more potent lymphokine-activated killer (LAK) cells for use in
      adoptive immunotherapy, pokeweed mitogen (PWM) was added to the culture medium
      for the initial 24-48 h of culturing. The proliferation rate of PWM-stimulated
      LAK cells reached about 1000-fold after 3-week culture. This rate was nearly the
      same as that of LAK cells stimulated by 10 ng/ml of OKT3, the mouse anti-CD3
      monoclonal antibody. However, the cytotoxicity of PWM-stimulated LAK cells was
      significantly more potent than that of OKT3-stimulated LAK cells. Phenotypic
      analysis revealed that PWM-stimulated LAK cells were CD3+CD56(+)-dominant while
      OKT3-stimulated LAK cells were CD3+CD56(-)-dominant. About half of CD3+CD56+ PWM
      stimulated LAK cells was CD8+. These results suggest that more efficient adoptive
      immunotherapy is possible by using high-dose PWM-stimulated LAK cells with more
      potent cytotoxicity. Interleukin-1 beta and tumor necrosis factor alpha were
      significantly increased in the culture media after 24-h incubation with 1
      micrograms/ml of PWM. Secretion of interferon-gamma was not enhanced by this
      concentration of PWM within 24 h. Therefore, PWM is considered to activate
      monocytes or macrophages to produce these cytokines in advance, influencing the
      proliferation and the cytotoxicity of LAK cells.

PMID- 1379579
TI  - Response time of broiler chickens to cimaterol: meat tenderness, muscle
      composition fiber size, and carcass characteristics.
AB  - The response time to cimaterol (CIM), a beta-adrenergic agonist, by broiler
      chickens for carcass characteristics, muscle composition, muscle fiber size,
      catheptic enzyme activity, and tenderness was determined. Two trials were
      conducted in which chickens were fed a control diet (CON) containing 0 ppm of CIM
      or a diet containing 1 ppm of CIM. Trial 1 consisted of 55, 31-d-old broiler
      chickens individually fed for up to 48 h. At 0, 6, 12, 18, 24, and 48 h, five CON
      and five CIM-fed chickens were killed. Trial 2 consisted of 160, 33-d-old broiler
      chickens group-fed for up to 14 d. At 2, 4, 6, 8, 10, 12, and 14 d, 10 CON and 10
      CIM-fed chickens were killed. The breast muscle (BM) and leg muscle (LM) weight,
      cathepsin B and L activities, DNA, RNA, and protein concentration, and BM shear
      force value (SFV) were measured in both trials. Thigh muscle (TM) SFV were
      measured in Trial 2 only. Fiber size of BM was measured (five birds per
      treatment) at d 2, 6, 10, and 14. In Trial 1, BM weight and SFV were lower in CIM
      fed birds at 6 h (P less than .05). In Trial 2 BM SFV were higher at d 8 (P =
      .06) and d 10 (P less than .05) in CIM-fed chickens. The SFV of CIM-fed chickens
      were higher at d 4, 8, 10, 12, and 14 (P less than .05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1379581
TI  - Electrocardiogram of the month. Premature ventricular complexes.

PMID- 1379580
TI  - Effect of recombinant porcine somatotropin and dietary protein on pancreatic
      digestive enzymes in the pig.
AB  - This study was conducted to determine the effect of daily recombinant porcine
      somatotropin (rpST) injection (0 or 120 micrograms/kg BW) and dietary CP level of
      the feed (14 or 26% CP) on pancreatic characteristics of growing pigs. Daily
      injection of rpST did not affect pancreatic weight (P = .885) but did decrease
      pancreatic amylase content (P = .005). The ratios of amylase:protein and
      amylase:trypsin were also lowered by daily rpST injection (P = .002 and P =
      .0002, respectively). There were protein x rpST and protein x rpST x sex
      interactions for the ratio of amylase:chymotrypsin. The CP content of the diet
      had a greater effect than the injection of rpST on pancreatic characteristics.
      Pigs consuming the 26% CP diet had significantly higher pancreatic weight (P =
      .003) and greater total pancreatic chymotrypsin (P = .006) than pigs consuming
      the 14% CP diet. The ratios of trypsin and chymotrypsin to DNA were also higher
      in pigs fed the 26% CP diet (P = .007 and P = .005, respectively). These
      responses were not influenced by sex. Recombinant porcine somatotropin seemed to
      have a slight effect on porcine pancreatic characteristics; however, dietary
      protein had a greater effect on pancreatic characteristics in market-weight hogs.

PMID- 1379583
TI  - Cloning, nucleotide sequence, and transcriptional analyses of the gene encoding a
      ferredoxin from Methanosarcina thermophila.
AB  - A mixed 17-mer oligonucleotide deduced from the N terminus of a ferredoxin
      isolated from Methanosarcina thermophila was used to probe a lambda gt11 library
      prepared from M. thermophila genomic DNA; positive clones contained either a 5.7-
      or 2.1-kbp EcoRI insert. An open reading frame (fdxA) located within the 5.7-kbp
      insert had a deduced amino acid sequence that was identical to the first 26 N
      terminal residues reported for the ferredoxin isolated from M. thermophila, with
      the exception of the initiator methionine. fdxA had the coding capacity for a
      6,230-Da protein which contained eight cysteines with spacings typical of 2[4Fe
      4S] ferredoxins. An open reading frame (ORF1) located within the 2.1-kbp EcoRI
      fragment also had the potential to encode a 2[4Fe-4S] bacterial-type ferredoxin
      (5,850 Da). fdxA and ORF1 were present as single copies in the genome, and each
      was transcribed on a monocistronic mRNA. While the fdxA- and ORF1-specific mRNAs
      were detected in cells grown on methanol and trimethylamine, only the fdxA
      specific transcript was present in acetate-grown cells. The apparent
      transcriptional start sites of fdxA and ORF1, as determined by primer extension
      analyses, lay 21 to 28 bases downstream of sequences with high identity to the
      consensus methanogen promoter.

PMID- 1379584
TI  - Characterization of the lipopolysaccharide O antigens of Actinobacillus
      pleuropneumoniae serotypes 9 and 11: antigenic relationships among serotypes 9,
      11, and 1.
AB  - The antigenic lipopolysaccharide O polysaccharides of capsular serotypes 9 and 11
      were examined by chemical, immunological, and nuclear magnetic resonance methods.
      Immunodiffusion tests carried out on these O antigens indicated that both
      contained common epitopes which were also shared by Actinobacillus
      pleuropneumoniae serotype 1. Chemical analysis and high-field nuclear magnetic
      resonance spectroscopy showed that the O antigens of serotypes 9 and 11 were high
      molecular-weight polymers consisting of a backbone of repeating trisaccharide
      units composed of alpha-L-rhamnopyranosyl and alpha-D-glucopyranosyl residues
      (2:1). One of the alpha-L-rhamnose units forms a branch point and is
      stoichiometrically substituted with terminal 2-acetamido-2-deoxy-beta-D-glucose
      residues in the serotype 11 O polysaccharide, but only to the extent of 25% in
      the serotype 9 O polysaccharide. Thus, the serotype 9 O polysaccharide contains
      two different repeating units: a tetrasaccharide unit with the same structure as
      that of the serotype 11 O polysaccharide and a trisaccharide unit: [formula: see
      text] where R = beta-D-GlcpNAc for serotype 1 and 11 O polysaccharides, and R = H
      (75%) and R = beta-D-GlcpNAc (25%) for serotype 9. The structure of the
      previously determined serotype 1 O polysaccharide (E. Altman, J.-R. Brisson, and
      M. B. Perry, Biochem. Cell. Biol. 64:17-25, 1986) is identical to that of the
      serotype 11 O polysaccharide. We propose a more complete serotyping scheme for A.
      pleuropneumoniae which includes designation of both the capsular (K) and O
      antigens.

PMID- 1379585
TI  - [Evaluation of a histochemical method specific for myosin ATPase activity in the
      masticatory muscles of the rat].
AB  - A biological study of masticatory muscle behaviour (Divry and Westphal, 1991)
      suggested the analysis of physiologic correlates (biologic parameters related to
      a behavioural event) such as histochemical reactions of muscular fibres studied
      by M-ATPase and SDH activities. For such investigations, routine methods are
      needed. In the present study, a modification of the original method of Tunell and
      Hart (1977) was used, in which three features of the original alkaline
      preincubation method (composition, incubation time and pH) were modified. These
      allowed a single step differentiation of the various fibre types found in rat
      masticatory muscles, for which the classical technics gave only a weak contrast,
      not suitable for image analysis. Acid preincubation was also tested but failed to
      give new information. By combining this modified technic with SDH staining
      (Nachlas, 1957) a classification of fibres into 12 theoretical types was
      proposed.

PMID- 1379582
TI  - Nucleotide sequences of the genes regulating O-polysaccharide antigen chain
      length (rol) from Escherichia coli and Salmonella typhimurium: protein homology
      and functional complementation.
AB  - In this article, we report on the nucleotide sequences of the rol genes of
      Escherichia coli O75 and Salmonella typhimurium LT2. The rol gene in E. coli was
      previously shown to encode a 36-kDa protein that regulates size distribution of
      the O-antigen moiety of lipopolysaccharide. The E. coli and S. typhimurium rol
      gene sequences consist of 978 and 984 nucleotides, respectively. The homology
      between the nucleotide sequences of these two genes was found to be 68.9%. Both
      the E. coli rol and S. typhimurium rol genes are transcribed counter to the
      histidine operon and code for deduced polypeptides of 325 and 327 amino acids,
      respectively. The S. typhimurium rol gene was previously identified to encode a
      protein of unknown function and to share a transcription termination region with
      his. The homology between these deduced polypeptide sequences was observed to be
      72%. A complementation test was performed in which the S. typhimurium rol gene
      was placed in trans with an E. coli plasmid (pRAB3) which encodes the O75 rfb
      gene cluster and not rol. The protein expressed from the S. typhimurium rol gene
      was found to regulate the distribution of the O75 O polysaccharide on the
      lipopolysaccharide of the host strain, E. coli S phi 874. The mechanism of Rol
      action may be independent of O antigen subunit structure, and its presence may be
      conserved in members of the family Enterobacteriaceae and other gram-negative
      bacilli that express O polysaccharides on their surface membrane.

PMID- 1379586
TI  - Monoclonal antibodies recognizing protease-generated neoepitopes from cartilage
      proteoglycan degradation. Application to studies of human link protein cleavage
      by stromelysin.
AB  - Monoclonal antibodies were raised that specifically recognize the NH2-terminal
      neoepitope sequence present in link protein cleavage products derived from
      stromelysin-degraded proteoglycan aggregate. Competitive enzyme-linked
      immunosorbent assay, using synthetic peptides as inhibitors, showed that one of
      these antibodies (CH-3) required, for antibody recognition, the free NH2-terminal
      amino acid isoleucine (residue 17 of the intact protein) in the sequence NH2
      IQAENG at the stromelysin cleavage site of link protein 3. Human proteoglycan
      aggregate was digested with recombinant human stromelysin, bovine chymotrypsin,
      bovine trypsin, and porcine elastase, and their respective link protein
      degradation products were tested for immunoreactivity with antibody CH-3. Only
      stromelysin- and chymotrypsin-generated link protein 3 were recognized by
      antibody CH-3. Both of these enzymes generate link protein NH2 termini with the
      sequence 17IQAENG. . .; hence these studies indicated that monoclonal antibody CH
      3 recognized this neoepitope sequence in only specific proteolytically modified
      link protein molecules. Since the occurrence of link protein 3 increases with
      aging, the incidence of CH-3 epitope in proteoglycans isolated from human knee
      articular cartilage of individuals of different ages was investigated. The
      prevalence of CH-3 epitope was found to be highest in newborn and adolescent
      articular cartilage samples. However, little CH-3 epitope was detected in older
      adult cartilage, although considerably more link protein 3 was present in these
      samples. These results suggest that additional proteolytic agents are responsible
      for the increased occurrence of link protein degradation products with aging.

PMID- 1379587
TI  - Cloning and expression of guanylin. Its existence in various mammalian tissues.
AB  - Guanylin (PNTCEICAYAACTGC) is a peptide recently isolated from the intestine, the
      actions of which appear to be mimicked by bacterial heat-stable enterotoxins
      (Currie, M. G., Fok, K. F., Kato, J., Moore, R. J., Hamra, F. K., Duffin, K. L.,
      and Smith, C. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 947-951). A cDNA clone
      encoding the peptide was isolated from a rat intestinal cDNA library using a
      degenerate oligonucleotide probe. The mRNA (approximately 0.8-0.9 kilobase)
      encoding the peptide contained an open reading frame of 115 amino acids,
      including an amino-terminal signal peptide. The carboxyl-terminal region of the
      predicted polypeptide contained a sequence identical to guanylin, but the 15
      amino acid peptide likely represents an artifact of previous acetic acid
      extraction methods, since an aspartate residue precedes the amino-terminal
      proline. A lysine-lysine dipeptide bond is one likely processing site of pro
      guanylin and would generate a 60-amino acid mature peptide. Other potential
      cleavage sites exist at single lysine and arginine residues, which could result
      in peptides ranging from 22 to 56 amino acids. Transfection of COS-7 cells with
      the guanylin cDNA resulted in the expression of a secreted protein of M(r)
      10,000. The expressed proguanylin failed to elevate cyclic GMP concentrations in
      human colonic T84 cells, but acetic acid treatment of pro-guanylin activated it
      and resulted in large elevations of cyclic GMP. Guanylin mRNA was prevalent in
      rat intestine but was also found in low abundance in adrenal gland, kidney, and
      uterus/oviduct. Guanylyl cyclase C, the apparent guanylin receptor, was found in
      abundant amounts in the intestine by Northern analysis, and by the polymerase
      chain reaction or cDNA cloning it was also found in adrenal gland, airway
      epithelial cells, brain, and olfactory and tracheal mucosa. Therefore, the ligand
      and apparent receptor (guanylyl cyclase C) both originate from mammalian genes,
      and are expressed in various mammalian tissues.

PMID- 1379589
TI  - Expression of the cystic fibrosis transmembrane conductance regulator gene can be
      regulated by protein kinase C.
AB  - Epithelial cells utilize at least two types of apical Cl- channels, the cAMP
      activated cystic fibrosis transmembrane conductance regulator (CFTR) and the
      Ca2+/calmodulin-dependent Cl- channel. While phorbal ester (PMA) activates only
      CFTR-dependent Cl- secretion and the Ca2+ ionophore A23187 only the
      Ca2+/calmodulin-dependent Cl- secretion, PMA and A23187 share the ability to down
      regulate expression of the CFTR gene at the transcriptional level. Since both PMA
      and A23187 can activate protein kinases, we hypothesized that protein kinase
      pathways may be involved in the regulation of CFTR gene expression. Exposure of
      HT-29 human colon carcinoma cells to the protein kinase C activator SC9 down
      regulated CFTR mRNA levels in a dose-dependent fashion, similar to that seen with
      PMA. The reduction in CFTR transcript levels by SC9 and PMA was blocked by H7, an
      inhibitor of protein kinases. In a similar fashion, the down-regulation of CFTR
      transcript levels by A23187 was blocked by H7 as well as staurosporine, another
      protein kinase inhibitor. Interestingly, both H7 and staurosporine themselves
      increased CFTR mRNA levels. Quantification of CFTR gene transcription rate showed
      a reduction by SC9 (similar to that with PMA and A23187) that was prevented by H7
      and that H7 by itself increased CFTR transcription. Together, these observations
      suggest that protein kinase pathways, likely including protein kinase C, are
      involved in the regulation of CFTR gene expression, with activation or inhibition
      of protein kinase activity down-regulating or up-regulating CFTR gene expression,
      respectively.

PMID- 1379588
TI  - Charged surface residues of FKBP12 participate in formation of the FKBP12-FK506
      calcineurin complex.
AB  - The mechanism of FK506 immunosuppression has been proposed to proceed by
      formation of a tight-binding complex with the intracellular 12-kDa FK506-binding
      protein (FKBP12). The FK506-FKBP12 complex then acts as a specific high-affinity
      inhibitor of the intracellular protein phosphatase PP2B (calcineurin),
      interrupting downstream dephosphorylation events required for T-cell activation.
      Site-directed mutagenesis of many of the surface residues of FKBP12 has no
      significant effect on its affinity for calcineurin. We have identified, however,
      three FKBP12 surface residues (Asp-37, Arg-42, and His-87) proximal to a solvent
      exposed segment of bound FK506 that may be direct contacts in the calcineurin
      complex. Site-directed mutagenesis of two of these residues decreases the
      affinity of FKBP12-FK506 for calcineurin (Ki) from 6 nM for wild-type FKBP12 to
      3.7 microM for a R42K/H87V double mutant, without affecting the peptidylprolyl
      isomerase activity or FK506 affinity of the mutant protein. These FKBP12
      mutations along with several substitutions on FK506 known to affect calcineurin
      binding form a roughly 100-A2 region of the FKBP12-FK506 complex surface that is
      likely to be within the calcineurin binding site.

PMID- 1379590
TI  - Expression of the amiloride-blockable Na+ channel by RNA from control versus
      aldosterone-stimulated tissue.
AB  - The amiloride-blockable Na+ channel was expressed in Xenopus oocytes injected
      with total RNA isolated from the toad urinary bladder. This system was used to
      investigate mechanisms that mediate the natriferic action of aldosterone.
      Incubation of the epithelium with aldosterone for 3 h doubled its channel
      activity but did not increase the ability of isolated RNA to express functional
      channels in oocytes. A 20-h incubation with the hormone produced an additional
      increase of Na+ transport across the intact epithelium and also augmented the
      channel activity expressed in oocytes by nearly 10-fold. The data are in
      agreement with our model that aldosterone enhances the apical Na+ permeability of
      tight epithelia by a short term activation of pre-existing channels, followed by
      chronic induction of new channel protein. Blocking methyl transfer reactions,
      previously shown to inhibit the natriferic action of aldosterone in tight
      epithelia, did not alter the basal or aldosterone-induced response in oocytes.

PMID- 1379591
TI  - A naturally occurring secreted form of fibroblast growth factor (FGF) receptor 1
      binds basic FGF in preference over acidic FGF.
AB  - Alternatively spliced variants of fibroblast growth factor receptor 1 mRNA are
      predicted to encode secreted forms and membrane-bound forms of receptors. The
      predicted amino acid sequences of these receptor variants differ in a portion of
      the extracellular region. In this study, we characterized the function of one of
      these splice variants which was predicted by its cDNA to be a secreted FGF
      receptor. We expressed this secreted form of the human FGFR1 (sFGFR1) in Chinese
      hamster ovary cells. The sFGFR1 protein oligomerized upon ligand binding.
      Surprisingly, the sFGFR1 preferentially bound basic FGF over acidic FGF. In cross
      linking experiments, the sFGFR1 showed higher binding affinity for basic FGF (Kd
      approximately 30 nM) than for acidic FGF (Kd greater than 300 nM). These results
      suggest that this secreted form of FGF receptor has an unusual ligand binding
      specificity that may be important for its biological role in vivo.

PMID- 1379593
TI  - Characterization of two high affinity human interleukin-8 receptors.
AB  - Interleukin 8 (IL-8) and melanocyte growth-stimulatory activity/gro (MGSA) are
      structurally related proinflammatory cytokines that are chemoattractants and
      activators of neutrophils. Recently, cDNA clones encoding a high affinity IL-8
      receptor (IL-8R-A) and a "low affinity" IL-8 receptor (IL-8R-B) have been
      isolated from human cDNA libraries. These two receptors have 77% amino acid
      identity and are members of the G protein-coupled superfamily of receptors with
      seven transmembrane domains. We have expressed these two receptors in mammalian
      cells and find that in this system both receptors bind IL-8 with high affinity
      (Kd approximately 2 nM). The receptor affinities differ for MGSA, however. IL-8R
      A binds MGSA with low affinity (Kd approximately 450 nM); IL-8R-B binds MGSA with
      high affinity (Kd approximately 2 nM). The transfected cells respond to ligand
      binding with a transient increase in the intracellular Ca2+ concentration. A Ca2+
      response is found for IL-8R-A following the binding of IL-8; no response is found
      for MGSA. A Ca2+ response for IL-8R-B follows the binding of both ligands. Blot
      hybridization with oligonucleotide probes specific for the two receptors shows
      that mRNA for both receptors is present in human neutrophils. Analysis of IL-8
      and MGSA binding data on neutrophils as well as Ca2+ response and desensitization
      data shows that the presence of these two IL-8 receptors on the cell surface can
      account for the profile of these two ligands on neutrophils.

PMID- 1379592
TI  - G protein antagonists. A novel hydrophobic peptide competes with receptor for G
      protein binding.
AB  - A substance P (SP) analog, [D-Pro4,D-Trp7,9,10] SP4-11, is known to inhibit the
      actions of various structurally unrelated messenger molecules as well as SP. Our
      studies on the effects of this peptide on the regulation of purified G proteins
      by receptor showed that at least some of the biological effects of the peptide
      can be explained by the ability of the peptide to block the activation of G
      proteins by receptors. Here we report that a novel truncated SP-related peptide,
      pGlu-Gln-D-Trp-Phe-D-Trp-D-Trp-Met-NH2, inhibited the activation of G(i) or G(o)
      by M2 muscarinic cholinergic receptor (M2 mAChR) or of Gs by beta-adrenergic
      receptor in the reconstituted phospholipid vesicles, assayed by receptor-promoted
      GTP hydrolysis. The inhibition by the peptide was apparently reversible and
      competitive with respect to receptor binding to G proteins; the inhibition could
      be overcome by increasing the concentration of receptor in the vesicles and was
      not altered by changes in the concentration of G protein. The competing effects
      of the peptide were used to analyze the effect of agonist on receptor-G protein
      interaction. The concentration change of muscarinic agonist did not alter the
      inhibitory effects of the peptide on M2 mAChR-promoted GTPase by G(o), which is
      consistent with the idea that agonist increases the regulatory efficiency of the
      receptor but does not alter its affinity for G proteins. This new group of
      compounds (G protein antagonists) is a promising tool to study receptor-G protein
      interaction quantitatively.

PMID- 1379594
TI  - Ligand specificity and heparin dependence of fibroblast growth factor receptors 1
      and 3.
AB  - The heparin-binding growth factors include a family of seven structurally related
      proteins that can potentially interact with four known high affinity receptors.
      We have cloned the murine homologues of fibroblast growth factor receptors 1 and
      3 (mFR1 and mFR3). To define the ligand specificity of these receptors, we have
      characterized their binding properties with respect to acidic and basic
      fibroblast growth factors (aFGF and bFGF, respectively) and their biologic
      activity with respect to aFGF, bFGF, FGF-4/K-FGF, and FGF-5. Unlike mFR1, which
      binds both aFGF and bFGF, mFR3 preferentially binds aFGF. mFR3-mediated
      mitogenicity also favors aFGF and FGF-4 with a 10-12-fold lower response to bFGF
      and no response to FGF-5. Both receptor binding and growth factor-mediated
      mitogenicity are dependent on heparin. Heparin-binding growth factor activity can
      thus be regulated by proteoglycans and by the type of FGF receptor expressed on
      the target cell.

PMID- 1379595
TI  - Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1).
AB  - Vascular cell adhesion molecule-1 (VCAM-1) was first identified as a protein that
      appears on the surface of endothelial cells after exposure to inflammatory
      cytokines. Through interaction with its integrin counter receptor VLA-4, VCAM-1
      mediates cell-cell interactions important for immune function. We have cloned and
      begun characterization of the promoter for the VCAM-1 gene. In a series of
      transfection assays into human umbilical vein endothelial cells (HUVECs), we find
      that silencers between positions -1.641 kilobases and -288 base pairs restrict
      promoter activity, and that treatment with tumor necrosis factor-alpha overcomes
      this inhibition and activates the promoter through two NF kappa B sites located
      at positions -77 and -63 base pairs of the VCAM-1 gene. This responsiveness
      appears cell-specific since constructs containing the VCAM-1 NF kappa B sites are
      not responsive to tumor necrosis factor alpha in the T-cell line Jurkat. The two
      VCAM-1 NF kappa B sites, which differ slightly in their sequence, form distinct
      complexes in gel retardation assays, suggesting that they interact with different
      NF kappa B-site binding proteins. The distribution of these proteins could then
      control activity of the NF kappa B sites. We conclude that the pattern of VCAM-1
      expression in HUVECs is controlled by a combination of these silencers and NF
      kappa B sites.

PMID- 1379596
TI  - Molecular cloning of the transmembrane component of the 13762 mammary
      adenocarcinoma sialomucin complex. A new member of the epidermal growth factor
      superfamily.
AB  - Ascites sublines of the 13762 rat mammary adenocarcinoma have a cell surface
      sialomucin complex composed of the sialomucin ascites sialoglycoprotein-1 (ASGP
      1) and the membrane-associated glycoprotein ASGP-2. The sialomucin complex is
      synthesized as a high M(r) precursor, pre-sialomucin complex (pSMC-1). To
      characterize the structure of the membrane-associated component of this complex,
      a lambda gt11 cDNA expression library was constructed using mRNA from 13762 rat
      mammary adenocarcinoma cells and screened with polyclonal antibody against ASGP
      2. The strongest antibody-binding clone, designated lambda ASGP2.9-1, had a 1.3
      kilobase (kb) insert, and hybridized to a 9-kb transcript in 13762 cell mRNA. The
      large size of this transcript was expected, since the estimated molecular mass of
      pSMC-1 is greater than 250 kDa. To obtain the full sequence of ASGP-2, a longer
      cDNA (5.4 kb), designated pASGP1/2.1, was subsequently cloned by screening a
      plasmid library with an oligonucleotide complementary to the 5' end of the phage
      insert. The amino acid sequence derived from nucleotide sequence of pASGP1/2.1
      showed a 12-amino acid identity with amino acid sequence obtained from the NH2
      terminus of ASGP-2, indicating the entire ASGP-2 coding region was included in
      the cDNA. Furthermore, an 18-amino acid identity with the NH2 terminus of a 6-kDa
      CNBr fragment of ASGP-2 was also observed in the cDNA sequence. The polypeptide
      contains several distinct domains, including a hydrophobic transmembrane domain,
      a short (20 residue) COOH-terminal cytoplasmic tail, and a large extracellular
      domain with 24 potential N-glycosylation sites. These properties correspond to
      features of ASGP-2 and pSMC-1 predicted by previous biochemical studies. Most
      interestingly, the extracellular domain contains two cysteine-rich sequences,
      each of which has a segment with strong similarities to proteins with epidermal
      growth factor activity. Since our recent studies show that ASGP-2 can modulate
      epidermal growth factor receptor phosphorylation activity, these results provide
      structural evidence to support the role of the heterodimeric sialomucin complex
      as a bifunctional modulator of cellular interactions and cell proliferation.

PMID- 1379598
TI  - Two novel human pancreatic lipase related proteins, hPLRP1 and hPLRP2.
      Differences in colipase dependence and in lipase activity.
AB  - We have isolated cDNAs coding for two novel human pancreatic lipase (hPL)-related
      human proteins, referred to as hPL-related proteins 1 and 2 (hPLRP1 and hPLRP2)
      and for hPL. The two novel proteins show an amino acid sequence identity to hPL
      of 68 and 65% for hPLRP1 and 2, respectively. All three proteins are secreted
      into the medium after transfection of COS cells with the corresponding cDNAs. The
      size of the three expressed proteins is similar and ranges between 45 and 50 kDa.
      The expressed hPLRP2 shows a lipolytic activity that is, however, in contrast to
      that of hPL only marginally dependent on the presence of colipase, whereas hPLRP1
      shows no activity in this assay. A Northern analysis of normal human pancreas
      mRNA shows that the expression levels of hPLRP1 and hPLRP2 are about 4-fold and
      24-fold lower, respectively, than that of hPL. hPLRP2 is, additionally, most
      closely related to a lipase reported to be expressed in mouse T-cells. A
      comparison of the sequences of the three proteins with sequences described as
      pancreatic lipases of other animal species shows three subfamilies of closer
      kinship. This suggests that the two novel proteins also exist in other species
      and that some of the sequences reported to be pancreatic lipase might more likely
      be the orthologues of hPLRP1 or hPLRP2 in those species.

PMID- 1379599
TI  - Microtubule-associated proteins 1A and LC2. Two proteins encoded in one messenger
      RNA.
AB  - The deduced amino acid sequence for the filamentous microtubule-associated
      protein (MAP) 1A, thought to be involved in stabilizing the mature neuronal
      cytoskeleton, has been determined from a series of overlapping cDNA clones.
      Though previously described as biochemically and immunologically distinct from
      MAP1B, we now demonstrate that MAP1A is structurally related to MAP1B, a protein
      associated with neurite outgrowth and process plasticity. The two MAPs exhibit
      regional amino acid sequence similarities spanning their potential microtubule
      binding domains placing both into a new MAP family. The cDNA sequence encoding
      MAP1A was also found to encode one of its associated light chains (LC) called
      LC2. Both proteins are found on a single mRNA in the same open reading frame and
      are translated as a pre-MAP1A/LC2-protein. The topological relationship between
      MAP1A and LC2 coding sequences is, therefore, identical to that previously shown
      for MAP1B and LC1 (Hammarback, J. A., Obar, R. A., Hughes, S. M., and Vallee, R.
      B. (1991) Neuron 7, 129-139). Based on these and earlier results, we conclude
      that LC1 and LC2 are structurally related polypeptides generated from distinct
      MAP polyprotein precursors but free to exchange between the two MAPs.

PMID- 1379597
TI  - Vinculin binding site mapped on talin with an anti-idiotypic antibody.
AB  - Vinculin and talin are major adhesion plaque components which interact in vitro
      and presumably in vivo. The amino acid sequence of talin is now known so details
      of its domain structure can be mapped. We localized vinculin binding sites in the
      talin sequence by overlaying peptide maps of talin with an anti-idiotypic
      vinculin antibody that recognizes talin and with 125I-vinculin. A rabbit injected
      only twice with vinculin and producing anti-vinculin antibodies spontaneously
      generated a second antibody that recognizes talin. Vinculin and anti-vinculin
      antibodies specifically compete with this second antibody for binding to talin as
      determined by solid-phase binding and overlay assays. The antibody is thus most
      likely an anti-idiotypic antibody which mimics a region of vinculin that
      interacts with talin. The binding site of the anti-idiotypic antibody on talin
      was mapped to the 196 amino acids spanning residues 1653 to 1848. A second
      vinculin binding site identified with an 125I-vinculin blot overlay technique was
      located between residues 483 and 1652. The observation that talin has two
      immunologically distinct vinculin binding sites suggests that vinculin may have
      two different talin binding sites or one "complex" site with two interacting
      regions.

PMID- 1379600
TI  - Sense and antisense cDNA transfection of CD36 (glycoprotein IV) in melanoma
      cells. Role of CD36 as a thrombospondin receptor.
AB  - Thrombospondin (TSP) is a multifunctional matrix and platelet glycoprotein that
      interacts with cell surfaces and may play a role in mediating cell adhesion,
      platelet aggregation, platelet-monocyte interactions, cell proliferation,
      angiogenesis, tumor metastasis, and protease generation. To clarify and confirm
      the function of CD36 (glycoprotein IV) as a TSP receptor, we now describe a
      transfected cell model using human melanoma cells genetically manipulated by
      sense or antisense cDNA transfection to express either high or near zero levels
      of CD36. Surface expression was confirmed by flow cytometry with monoclonal anti
      CD36 IgG and quantified by measuring radiolabeled antibody binding. Bowes
      melanoma cells, which in their wild type did not express CD36 and did not bind
      radiolabeled TSP, when transfected with the sense construct bound TSP in a 1:1
      stoichiometric ratio with CD36 expression. Conversely, C32 melanoma cells, which
      in their wild type expressed high levels of CD36 and bound radiolabeled TSP at a
      1:1 stoichiometric ratio, did not express CD36 and did not bind TSP when
      transfected with an antisense construct. In addition, transfected Bowes cells and
      wild type C32 cells, unlike wild type Bowes cells, adhered to activated platelets
      in a TSP-dependent manner. These data, i.e. the gain of function with sense cDNA
      transfection and loss of function with antisense transfection, strongly support
      the TSP receptor function of CD36. The distribution of this protein in vascular
      cells and tissues and observations that it may participate in signal transduction
      events suggest that TSP-CD36 interactions may play a role in mediating some of
      the pathophysiological processes associated with TSP.

PMID- 1379601
TI  - Signal transduction by the epidermal growth factor receptor is attenuated by a
      COOH-terminal domain serine phosphorylation site.
AB  - It has been proposed that the acute desensitization of epidermal growth factor
      receptor (EGF-R) function can be accounted for, in part, by the effect of EGF to
      increase phosphorylation of the receptor at Ser1046/7 (Countaway, J.L., Nairn,
      A.C., and Davis, R.J. (1992) J. Biol. Chem. 267, 1129-1140). Here, we show that
      the mutational removal of this phosphorylation site causes an activation of EGF-R
      function and a potentiation of signal transduction. The mechanism of potentiation
      results from 1) defective down-regulation of the EGF-R when cells are incubated
      with high concentrations of EGF; and 2) increased EGF-stimulated tyrosine
      phosphorylation. The increased EGF-stimulated phosphorylation is associated with
      an alteration of the apparent specificity of tyrosine phosphorylation and is
      independent of the down-regulation defect. Together, these data strongly support
      the hypothesis that Ser1046/7 is a biologically significant site of regulatory
      phosphorylation of the EGF-R.

PMID- 1379602
TI  - Characterization of a keratinocyte-specific extracellular epitope of desmoglein.
      Implications for desmoglein heterogeneity and function.
AB  - Despite the presumed importance of desmoglein, a 160-kDa glycoprotein, in
      desmosome formation and its possible involvement in certain blistering skin
      diseases, the precise location and function of this protein have not yet been
      firmly established. We describe here the characterization of a new monoclonal
      antibody, AE23, against an extracellular epitope of desmoglein. Both the AE23
      epitope and another epitope, defined by the previously characterized DG3.4
      antibody, reside on a 160-kDa human epidermal desmoglein as evidenced by their
      identical solubility profile, their coexistence in a 130-kDa desmoglein
      degradative product, their coadsorption by an AE23 immunoaffinity column, and the
      identical changes in the two antigens' electrophoretic mobility after air
      oxidation and deglycosylation. The AE23 epitope is resistant to various
      endoglycosidases, suggesting that sugar moieties are not involved.
      Characterization of several proteolytic fragments of this epidermal desmoglein
      enabled us to map the DG3.4 epitope to a 96-kDa intracellular domain and the AE23
      epitope to an extracellular domain flanked by the plasma membrane and the distal
      N-glycosylation site(s). However, these two epitopes do not always coexist on the
      same desmoglein molecule. For example, tissue surveys showed that although the
      DG3.4 epitope is present in the desmogleins of all epithelial cell types, the
      AE23 epitope is limited to normal keratinocytes. Moreover, electron microscopic
      localization data indicate that whereas the DG3.4 epitope is detected in the
      submembranous plaques of desmosomes, the AE23 epitope is present in the
      intercellular space of both desmosomal and nondesmosomal areas. These results
      raise the possibility that there exist several biochemically closely related
      isoforms of desmoglein, one (AE23+/DG3.4+) restricted to epidermal desmosomes,
      one (AE23+/DG3.4-) uniformly distributed along the keratinocyte cell surface, and
      another (AE23-/DG3.4+) present in desmosomes of simple epithelia and basal cells
      of cultured keratinocytes. The uniform distribution of at least one desmoglein
      related antigen in the intercellular space of keratinocytes coupled with the
      realization that different isoforms of desmogleins form a subfamily of cadherins
      suggest that desmoglein(s) may play a more general role in keratinocyte adhesion
      than previously appreciated.

PMID- 1379604
TI  - Sharing of antigenic epitopes between synaptophysin and granulophysin.
AB  - The immunological crossreactivity between the two granule-specific membrane
      glycoproteins, synaptophysin and granulophysin, was studied using a series of
      site-specific monoclonal and polyclonal antibodies. The epitope relatedness of
      six monoclonal antibodies against granulophysin was examined by competitive
      ELISA. The antibodies are shown to recognize distinct, but overlapping epitopes
      within a compact region that is constructed by the three-dimensional
      configuration of the molecule. All these antibody clones also recognize rat
      neuronal synaptophysin. Two monoclonal antibodies against synaptophysin, of which
      one is the well-characterized SY38 antibody, directed against the carboxy
      terminal of the molecule, are also shown to react with granulophysin.
      Characterized polyclonal antibodies against different peptide antigens of
      synaptophysin failed to recognize granulophysin. Synaptophysin and granulophysin
      are distinctly recognized in brain cell (white matter) and the pituitary both
      qualitatively and quantitatively. Based on these and other observations, it is
      suggested that the repeat motif in the cytoplasmic tail of synaptophysin
      represents an immunodominant construct that is the target for the observed
      crossreactive antibodies and that a similar tertiary construct has been preserved
      in granulophysin and in other transmembrane proteins.

PMID- 1379603
TI  - Regulation of gene expression by SPARC during angiogenesis in vitro. Changes in
      fibronectin, thrombospondin-1, and plasminogen activator inhibitor-1.
AB  - Angiogenesis in vitro, the formation of capillary-like structures by cultured
      endothelial cells, is associated with changes in the expression of several
      extracellular matrix proteins. The expression of SPARC, a secreted collagen
      binding glycoprotein, has been shown to increase significantly during this
      process. We now show that addition of purified SPARC protein, or an N-terminal
      synthetic peptide (SPARC4-23), to strains of bovine aortic endothelial cells
      undergoing angiogenesis in vitro resulted in a dose-dependent decrease in the
      synthesis of fibronectin and thrombospondin-1 and an increase in the synthesis of
      type 1-plasminogen activator inhibitor. SPARC decreased fibronectin mRNA by 75%
      over 48 h, an effect that was inhibited by anti-SPARC immunoglobulins. Levels of
      thrombospondin-1 mRNA were diminished by 80%. Over a similar time course, both
      mRNA and protein levels of type 1-plasminogen activator inhibitor (PAI-1) were
      enhanced by SPARC and the SPARC4-23 peptide. The effects were dose-dependent with
      concentrations of SPARC between 1 and 30 micrograms/ml. In contrast, no changes
      were observed in the levels of either type I collagen mRNA or secreted
      gelatinases. Half-maximal induction of PAI-1 mRNA or inhibition of fibronectin
      and thrombospondin mRNAs occurred with 2-5 micrograms/ml SPARC and approximately
      0.05 mM SPARC4-23. Strains of endothelial cells that did not form cords and tubes
      in vitro had reduced or undetectable responses to SPARC under identical
      conditions. These results demonstrate that SPARC modulates the synthesis of a
      subset of secreted proteins and identify an N-terminal acidic sequence as a
      region of the protein that provides an active site. SPARC might therefore
      function, in part, to achieve an optimal ratio among different components of the
      extracellular matrix. This activity would be consistent with known effects of
      SPARC on cellular morphology and proliferation that might contribute to the
      regulation of angiogenesis in vivo.

PMID- 1379606
TI  - Direct sequencing of large flavivirus PCR products for analysis of genome
      variation and molecular epidemiological investigations.
AB  - The polymerase chain reaction (PCR) was used to amplify viral cDNAs from selected
      regions of dengue genomic RNA by using appropriate 'consensus' primers. DNA
      amplicons containing the structural genes from all 4 dengue serotypes were
      prepared and directly sequenced using dengue-virus-specific primers. This method
      can characterize reliably flavivirus field isolates at the molecular level
      without extensive virus propagation and molecular cloning, and will be a valuable
      tool for molecular epidemiological studies.

PMID- 1379605
TI  - Disulfide-linked and noncovalent dimers of p185HER-2 in human breast carcinoma
      cells.
AB  - Enhanced levels of disulfide-linked dimers of the neu oncogene product have been
      suggested to be associated with the transformed state [Weiner DB, Liu J, Cohen
      JA, Williams WV, Greene MI: Nature 338:230-231, (1989)]. We, therefore,
      investigated the properties of the dimeric forms of p185HER-2/neu from the human
      breast carcinoma cell line, SK-BR-3. We found disulfide-linked dimers as well as
      noncovalently associated dimers that were detected by cross-linking with
      bis(sulfosuccinimidyl) suberate (BS3). However, the disulfide-linked dimers did
      not exist in intact cells, since they were eliminated when the cells were lysed
      in the presence of the alkylating agent, sodium iodoacetate. Moreover, the
      disulfide-linked dimeric molecules were not the activated form of p185HER-2 since
      they incorporated about the same level of phosphate in an in vitro kinase
      reaction as the monomeric molecules. In contrast, the noncovalent dimers appeared
      to be present on the surface of intact cells and were phosphorylated at levels at
      least tenfold higher than monomers in an in vitro kinase reaction.

PMID- 1379607
TI  - Suppression of experimental autoimmune encephalomyelitis by oral administration
      of myelin basic protein. V. Hierarchy of suppression by myelin basic protein from
      different species.
AB  - We have been investigating the suppression of experimental autoimmune
      encephalomyelitis (EAE) by oral tolerization to autoantigens. In the present
      study the tolerizing effect of orally administered myelin basic protein (MBP)
      from different species was examined in the Lewis rat, Hartley guinea pig, and
      SJL/J mouse model of EAE. Animals were fed guinea pig, rat, bovine, human or
      mouse-MBP and then immunized with the homologous species of MBP or myelin: Lewis
      rats were immunized with rat MBP, Hartley guinea pigs with guinea pig-MBP, and
      SJL/J mice with mouse myelin. Clinical expression of EAE and delayed-type
      hypersensitivity (DTH) responses to MBP were assessed. In each species,
      suppression of disease and DTH responses were most pronounced by tolerization
      with the homologous species of MBP. In addition, cross-species tolerization was
      observed in each species and in general was less suppressive than homologous MBP
      although in some instances MBP from a heterologous species was as effective as
      tolerization with the homologous species. We also studied guinea pig-MBP induced
      EAE in the Lewis rat because it is a widely studied model of EAE and found that
      oral tolerization with guinea pig MBP was as suppressive as rat MBP. Of note is
      that oral tolerization with mouse MBP suppressed myelin-induced EAE in the SJL
      mouse in which autoimmunity to proteolipid protein appears to play a primary
      role, suggesting that antigen-driven bystander suppression following oral
      tolerization with autoantigens (Miller et al., 1991b) may be an important
      contributing mechanism for suppression of EAE following oral tolerization with
      MBP in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379608
TI  - TCR peptide therapy decreases the frequency of encephalitogenic T cells in the
      periphery and the central nervous system.
AB  - The V beta 8 CDR2 consensus peptide, residues 44-54, is highly effective in the
      treatment of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis
      rats. To monitor immunological changes during EAE resulting from TCR peptide
      therapy, the frequencies of encephalitogenic and regulatory T cells were
      quantitated in lymph nodes, blood, and spinal cord. The frequency of T cells
      specific for basic protein and its major encephalitogenic epitope, residues 72
      89, increased during EAE to about 1 cell per 100,000 lymph node or blood cells at
      the peak of clinical disease, and then declined. In contrast, the frequency of
      these T cells in spinal cord was highest, 50 per 100,000, prior to onset of
      clinical signs, and then decreased rapidly prior to spontaneous recovery.
      Injection of 100 micrograms of TCR V beta 8-44-54 peptide caused a decrease
      within 1-5 days in the frequencies of guinea pig basic-protein (GP-BP) and 72-89
      reactive T cells in blood and spinal cord, and in the total number of
      infiltrating cells in spinal cord. In lymph nodes, 72-89-reactive T cells
      decreased as T cells specific for a protective epitope, residues 55-69 of GP-BP
      increased, suggesting epitope switching at the site of GP-BP immunization.
      Conversely, the frequency of T cells specific for the V beta 8-44-54 peptide
      increased, especially in blood and spinal cord, whereas T cell frequencies to
      control antigens were unchanged. These data document the critical presence of
      encephalitogenic T cells within the spinal cord during clinical EAE, and
      demonstrate that rapid and profound changes in T cell frequencies in the
      periphery and spinal cord are triggered by TCR peptide therapy.

PMID- 1379609
TI  - Retroviral-mediated transfer of the human glucocerebrosidase gene into cultured
      Gaucher bone marrow.
AB  - Gaucher disease, a lysosomal glycolipid storage disorder, results from the
      genetic deficiency of an acidic glucosidase, glucocerebrosidase (GC). The
      beneficial effects of allogeneic bone marrow transplantation (BMT) for Gaucher
      disease suggest that GC gene transduction and the transplantation of autologous
      hematopoietic stem cells (gene therapy) may similarly alleviate symptoms. We have
      constructed a retroviral vector, L-GC, produced by a clone of the amphotropic
      packaging cell line PA317, which transduces the normal human GC cDNA with high
      efficiency. Whole-marrow mononuclear cells and CD34-enriched cells from a 4-yr
      old female with type 3 Gaucher disease were transduced by the L-GC vector and
      studied in long-term bone marrow culture (LTBMC). Prestimulation of marrow with
      IL-3 and IL-6, followed by co-cultivation with vector-producing fibroblasts,
      produced gene transfer into 40-45% of the hematopoietic progenitor cells. The
      levels of GC expression in progeny cells (primarily mature myelomonocytic)
      produced by the LTBMC were quantitatively analyzed by Northern blot, Western
      blot, and glucocerebrosidase enzyme assay. Normal levels of GC RNA,
      immunoreactive protein, and enzymatic activity were detected throughout the
      duration of culture. These studies demonstrate that retroviral vectors can
      efficiently transfer the GC gene into long-lived hematopoietic progenitor cells
      from the bone marrow of patients with Gaucher disease and express physiologically
      relevant levels of GC enzyme activity.

PMID- 1379610
TI  - Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to
      bone marrow stroma.
AB  - Hematopoietic stem cell interaction with elements of the underlying stroma is
      essential for sustained normal hematopoiesis. Here we have determined that
      adhesion receptors in the integrin family play a role in promoting adhesion of
      human hematopoietic stem cells to cultured human marrow stromal cells. Enriched
      CD34hi progenitor cells expressed VLA-4, VLA-5, and at least one or more beta 2
      integrins. Homogeneous marrow stromal cell monolayers capable of supporting
      proliferation of cocultivated CD34hi cells expressed VCAM-1 and fibronectin
      (ligands for VLA-4 and VLA-5) as well as ICAM-1 (ligand for LFA-1 and Mac-1).
      Adhesion-blocking experiments indicated that VLA-4/VCAM-1, VLA-5/fibronectin, and
      beta 2-integrin/ICAM-1 pathways all are important for CD34hi cell attachment to
      stromal cells. Consistent with this suggestion, IL-1 stimulation of stromal cells
      caused both increased VCAM-1 and ICAM-1 expression and increased attachment by
      CD34hi bone marrow cells. In addition, CD34hi cells utilized VLA-4 to adhere to
      purified VCAM-1 and employed VLA-5 (and to a lesser extent VLA-4) to adhere to
      purified fibronectin. Together these results suggest that CD34hi stem cells may
      utilize multiple integrin-mediated adhesion pathways to localize within
      specialized microenvironmental niches created by marrow stromal cells.

PMID- 1379611
TI  - Experimental allergic encephalomyelitis in cynomolgus monkeys. Quantitation of T
      cell responses in peripheral blood.
AB  - Chronic relapsing-remitting experimental allergic encephalomyelitis (EAE) was
      induced in cynomolgus monkeys by a single immunization with a homogenate of human
      brain white matter (BH) in adjuvant. Proliferative T lymphocyte responses to BH,
      to myelin basic protein (MBP), but not to proteolipid protein, were detected in
      peripheral blood mononuclear cells (PBMC) of all animals and persisted until
      their death or, in surviving animals, for greater than 10 mo postimmunization.
      Responses of higher magnitude tended to be associated with fatal, compared with
      nonfatal, episodes of clinical EAE. The frequency of MBP-reactive T cells in PBMC
      of animals with acute EAE was quantitated with a soft agar colony system; the
      ratio of T cells that proliferated specifically to MBP was estimated at between 5
      and 20 per 10(6) PBMC. A similar frequency of peptide-specific T cells was
      estimated from PBMC of monkeys immunized with a synthetic 14-mer peptide
      corresponding to a region near the carboxy terminus of MBP. Thus, autoantigen
      reactive T cells can be detected in the circulation throughout the course of
      chronic EAE, are predictive of disease severity, and occur at a frequency similar
      to that estimated to be present in humans with multiple sclerosis.

PMID- 1379612
TI  - Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin
      mRNA.
AB  - The mammalian brain is considered to be poorly responsive to thyroid hormone
      after the so called "critical periods" of brain development, which occur in the
      rat before postnatal days 15-20. In a previous work (Munoz, A., A. Rodriguez
      Pena, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol.
      Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose
      expression is influenced by early neonatal hypothyroidism and thyroid hormone
      treatment. In the present work we show that adult-onset hypothyroidism leads to a
      reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and
      killed three months later showed a decreased RC3 mRNA concentration in the
      cerebral cortex and striatum. The same effect was observed in animals made
      hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression
      was normal when hypothyroid animals were treated with T4 five days before being
      killed. In contrast, the mRNA encoding myelin proteolipid protein showed no
      changes in either experimental situation. RC3 mRNA levels were not affected by
      food restriction demonstrating that the effect of hypothyroidism was not related
      to the lack of weight gain. The control of RC3 mRNA is so far the only molecular
      event known to be regulated by thyroid hormone once the critical periods of brain
      development are over and could represent a molecular correlate for the age
      independent, reversible alterations induced by hypothyroidism in the adult brain.

PMID- 1379613
TI  - Localization of cystic fibrosis transmembrane conductance regulator mRNA in human
      fetal lung tissue by in situ hybridization.
AB  - The fetal pulmonary epithelium secretes fluid. Cl transport is presumed to
      provide the driving force for net fluid secretion, although the cellular
      mechanisms have not been well identified in the fetus. The cystic fibrosis
      transmembrane conductance regulator (CFTR) is a cAMP- and nucleoside triphosphate
      regulated Cl channel; mutations in CFTR cause cystic fibrosis. We hypothesized
      that if CFTR is involved in fetal lung fluid transport, the fetal pulmonary
      epithelium should express CFTR mRNA. We used the technique of in situ
      hybridization with 3H-anti-sense and, as a control, 3H-sense CFTR cRNA probes to
      localize CFTR mRNA in human fetal lung tissue and cultured lung explants and
      determine when in gestation it is expressed. Epithelial cells of both first and
      second trimester lung tissues expressed CFTR mRNA. A decreasing gradient of CFTR
      mRNA expression was present from the proximal to the distal pulmonary epithelium.
      Cultured second trimester lung tissue explants expressed more CFTR mRNA than the
      uncultured starting tissue, suggesting CFTR gene expression increased during the
      five days in culture. Furthermore, alveolar type II cells in cultured explants
      expressed CFTR mRNA, suggesting that these cells are Cl-secretory and may be
      involved in lung fluid transport. These data confirm that CFTR mRNA is expressed
      in the human fetal pulmonary epithelium, consistent with the Cl-secretory
      properties of the fetal lung.

PMID- 1379614
TI  - Evidence for reactive nitrogen intermediates in killing of staphylococci by human
      neutrophil cytoplasts. A new microbicidal pathway for polymorphonuclear
      leukocytes.
AB  - In anucleate, granule-poor, motile fragments from human blood neutrophils
      (cytokineplasts; CKP), the nitric oxide synthase inhibitor N omega-monomethyl-L
      arginine (NMMA) produced a modest decrease in uptake of staphylococci from
      supernatants (P less than 0.02, n = 7), and a marked decrease in the killing of
      cytoplast-associated bacteria (P less than 0.001, n = 7). After 60 min of
      incubation with bacteria, NMMA-treated cytoplasts had a mean of over 3.5 times as
      many live, CKP-associated staphylococci as did controls (51% of the inocula
      versus 14%), despite having taken up fewer. Effects on both uptake and killing
      were reversible by L-arginine but not by D-arginine. Results were the same with
      other granule-poor cytoplasts (U-cytoplasts, U-CYT), which, unlike CKP, retain
      activatable oxidase activity. Killing by intact PMN, including those from a
      patient with chronic granulomatous disease, was not inhibited by NMMA. Thus, the
      ability to discern effects of NMMA correlated with the paucity of granules,
      without regard to the presence or absence of activatable oxidase. We propose that
      the generation of reactive nitrogen intermediates serves as an additional
      microbial killing pathway in PMN, and that cytoplasts can be used to help
      delineate the spectrum of susceptible targets.

PMID- 1379615
TI  - Determinants of aortic cyclic guanosine monophosphate in hypertension induced by
      chronic inhibition of nitric oxide synthase.
AB  - Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation
      by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble
      and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro
      L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase
      inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were
      tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10,
      20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a
      time- and dose-dependent increase in blood pressure. The total heart weight/body
      weight ratio did not change in any group, despite the hypertension. The plasma
      levels of cGMP did not change significantly in any group, and were correlated
      with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased
      in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating
      in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four
      highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was
      positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40).
      Intravenous L-arginine decreased arterial blood pressure and reversed the decline
      in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly
      increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent
      kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with
      L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic
      cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase:
      soluble guanylate cyclase activity and to a minor extent on particulate guanylate
      cyclase activity.

PMID- 1379616
TI  - Polymerase chain reaction localization of constitutive nitric oxide synthase and
      soluble guanylate cyclase messenger RNAs in microdissected rat nephron segments.
AB  - Stimulation of the release of nitric oxide (NO) in the kidney has been shown to
      result in renal hemodynamic changes and natriuresis. NO is a potent stimulator of
      soluble guanylate cyclase, leading to an increase of cyclic GMP. The precise
      localization of NO synthase and soluble guanylate cyclase in the renal structure
      is not known. In this study, the microlocalization of mRNAs coding for
      constitutive NO synthase and soluble guanylate cyclase was carried out in the rat
      kidney, using an assay of reverse transcription and polymerase chain reaction in
      individual microdissected renal tubule segments along the nephron, glomeruli,
      vasa recta bundle, and arcuate arteries. A large signal for constitutive NO
      synthase was detected in inner medullary collecting duct. Small signals were
      detected in inner medullary thin limb, cortical collecting duct, outer medullary
      collecting duct, glomerulus, vasa recta, and arcuate artery. Soluble guanylate
      cyclase mRNA is expressed largely in glomerulus, proximal convoluted tubule,
      proximal straight tubule, and cortical collecting duct, and in small amounts in
      medullary thick ascending limb, inner medullary thin limb, outer medullary
      collecting duct, inner medullary collecting duct, and the vascular system. Our
      data demonstrate that NO can be produced locally in the kidney, and that soluble
      guanylate cyclase is widely distributed in glomerulus, renal tubules, and the
      vascular system.

PMID- 1379617
TI  - Nitric oxide production in host-versus-graft and graft-versus-host reactions in
      the rat.
AB  - The present study was designed to determine whether .N = O produced in vivo
      during the rejection of histoincompatible tissues might permit serum NO2-/NO3-
      levels to serve as markers of a rejection reaction. Rat syngeneic and allogeneic
      liver, heart, bone marrow/spleen cell, small bowel, skin, and sponge matrix
      grafts were performed and the stable end-products of .N = O, NO2-/NO3-, were
      serially assayed in the serum of the grafted animals. A significant rise of serum
      NO2-/NO3- levels in the allografted animals preceded the onset of clinical signs
      of rejection or graft-versus-host disease, with the exception of the skin and
      sponge matrix graft models, where elevated serum NO2-/NO3- levels were never
      observed. In all transplant models, normal serum NO2-/NO3- levels were observed
      at all times in animals that received syngeneic grafts. Furthermore, treatment of
      allograft recipients with the immunosuppressive agents FK 506 or cyclosporine A
      inhibited .N = O production. Determination of serum creatinine levels
      demonstrated that the elevated serum NO2-/NO3- levels were not caused by kidney
      dysfunction. Serum NO2-/NO3- levels might be useful early serum markers of the
      initiation of a rejection reaction or graft-versus-host disease when functional
      markers of graft dysfunction are not apparent.

PMID- 1379618
TI  - Growth and morphological changes in the stomach of newborn pigs during the first
      three days after birth.
AB  - Growth and morphological changes in the stomach of newborn pigs were examined
      during the first 3 days after birth. The stomach grew disproportionately faster
      than the body as a whole during this period. The growth was due to hyperplasia
      and hypertrophy during the first day and mainly to hyperplasia thereafter as
      gastric DNA content increased progressively after birth, and the protein:DNA and
      RNA:DNA ratios increased only on the first day. Histological and morphometric
      analyses revealed that the growth was more pronounced in the gastric body region
      than in the cardiac and pyloric regions, and more pronounced in the mucosal layer
      than in other layers. The percentage of mucosal volume occupied by parietal cells
      (volume density) and the number of parietal cells per unit volume of gastric
      mucosa (numerical density) increased significantly 3 days after birth in the
      cardiac and body regions, but not in the pyloric region, of the stomach. The
      observed morphological changes coincide with the known pattern of functional
      maturation during the immediate postnatal period. It is suggested that a high
      level of circulating gastrin and oral ingestion of milk-derived growth factors in
      the newborn pig contribute to these changes.

PMID- 1379619
TI  - The c-kit proto-oncogene in normal and malignant human hematopoiesis.
AB  - The c-kit proto-oncogene encodes a tyrosine kinase receptor (KIT) which is
      expressed on many types of human cells. Numerous studies attest to the importance
      of the c-kit receptor and its ligand, known variously as stem cell factor (SCF),
      mast cell growth factor (MGF), Steel factor (SF), or kit ligand (KL) (the
      nomenclature we prefer), in the development of human hematopoietic cells. KL,
      which is produced in membrane-bound and soluble forms by bone marrow stromal
      cells, acts on pre-colony forming units (pre-CFU) and CFU cells. In synergistic
      combination with other cytokines, KL enhances the growth of myeloid progenitor
      cells. However, using an antisense oligodeoxynucleotide strategy to disrupt c-kit
      function, we have demonstrated that the KL-KIT complex is of greatest importance
      for generation and/or proliferation of normal human erythropoietic progenitor
      cells. In malignant hematopoietic cells, the complex also appears to be important
      for growth of granulocyte/macrophage (GM) CFU as well.

PMID- 1379620
TI  - Differentiation profiles of normal blast cell colonies derived from mononucleated
      cells, T cell depleted nonadherent cells and CD33-negative, CD34-positive normal
      human bone marrow cells.
AB  - Blast cell colonies can be grown reproducibly in methylcellulose from normal
      human mononuclear bone marrow cells (MNC) in the presence of 30% human plasma, 1
      U human recombinant erythropoietin and 10% of medium conditioned by
      phytohemagglutinin stimulated leukocytes as a source of growth factors. The
      colonies can be recognized by inverted microscopy by their display of highly
      refractile cytoplasmic structures that resemble small vacuoles. A proportion of
      cells within these colonies remains CD34-positive (CD34+). The blast-like
      morphology of these cells was sustained for at least 14 to 21 days. The frequency
      of blast cell colony forming units (CFU-BL) can be increased by a series of
      separation procedures to produce E-rosette depleted, nonadherent cells (E-NAC),
      CD34+ cells and CD33-CD34+ cells. The mean number of CFU-BL per 10(5) cells was
      1.9 +/- 1.6 in MNC, 5.7 +/- 2.7 in E-NAC, 108 +/- 51 in CD34+ cells and 112 +/-
      109 in CD33-CD34+ cells. The enrichment procedures were not specific for CFU-BL
      but also resulted in a similar increase of multilineage and single lineage
      progenitors. The relative proportions of CFU-BL and other progenitors remained
      unchanged among these subpopulations. The size of individual blast cell colonies
      on day 16 varied from 20 to 1,600 cells. After 14 to 21 days, cells within blast
      cell colonies acquired mature morphological features. The majority of blast cell
      colonies developed into multilineage colonies (62%); some (38%) were restricted
      to a single hemopoietic lineage. Larger blast cell colonies had a higher
      probability of developing into multilineage colonies than smaller blast cell
      colonies.

PMID- 1379622
TI  - The 23S/5S ribosomal RNA genes (rrl/rrf) are separate from the 16S ribosomal RNA
      gene (rrs) in Borrelia burgdorferi, the aetiological agent of Lyme disease.
AB  - DNA fragments containing the rRNA genes for Borrelia burgdorferi strain B31 were
      cloned in bacteriophage lambda EMBL3. A restriction map of the fragments was
      constructed and the organization of the rRNA genes was determined by Southern
      hybridization. One genomic DNA fragment contained a single copy of the rrs
      sequence and another cloned fragment contained both rrl and rrf sequences. The
      results revealed that the rrs gene is located separately from the set of rrl/rrf
      genes, suggesting that these rRNA genes are expressed independently in B.
      burgdorferi.

PMID- 1379621
TI  - Genetic linkage analysis of the murine developmental mutant velvet coat (Ve) and
      the distal chromosome 15 developmental genes Hox-3.1, Rar-g, Wnt-1, and Krt-2.
AB  - We have identified restriction fragment length polymorphisms between Mus musculus
      and Mus spretus for the Chromosome 15 loci Hox-3, Wnt-1, Krt-2, Rar-g, and Ly-6.
      We followed the inheritance of these alleles in interspecific genetic test
      crosses between velvet coat (Ve) heterozygotes and M. spretus. The results
      suggest a gene order and recombination distances (in cM) of Ly-6-22-Wnt-1-2
      Ve/Krt-2/Rar-g-3-Hox-3. No recombination was found between Ve, Krt-2, and Rar-g.
      The data also provide evidence for the hypothesis of a large-scale genomic
      duplication involving homologous gene pairs on mouse Chromosomes 15 and 11.

PMID- 1379623
TI  - Detection of micro-organisms in soil after in situ hybridization with rRNA
      targeted, fluorescently labelled oligonucleotides.
AB  - rRNA sequences were used as targets for synthetic oligonucleotides labelled with
      the fluorescent dye tetramethylrhodamine isothiocyanate (Tritc) for in situ
      hybridizations to detect micro-organisms directly in soils that have different
      contents of soil minerals and organic material. Introduced Pseudomonas aeruginosa
      cells were directly fixed in soils and applied to slides after separation of
      large soil minerals only. Remaining soil minerals (clay minerals) and organic
      material (up to 8%) did not significantly interfere with signal expression after
      hybridization. Background signals were mainly caused by autofluorescence of
      organic material. Non-specific binding of labelled oligonucleotides to soil
      particles was not observed. In situ detection of introduced cells of Pseudomonas
      cepacia in a sandy loam spiked with a mixture of selected soil micro-organisms
      was possible after hybridization with a specific probe. Analysis of natural
      bacterial populations in soil, however, was not possible by in situ hybridization
      without activation of these micro-organisms by adding nutrients. Growing cells,
      e.g. Streptomyces scabies hyphae growing in amended soil, were easily detected.

PMID- 1379624
TI  - Bovine rotavirus segment 5 protein expressed in the baculovirus system interacts
      with zinc and RNA.
AB  - The cDNA sequence of genomic segment 5 of bovine rotavirus (RF strain) has been
      inserted into baculovirus transfer vectors, downstream of the polyhedrin
      promotor. Recombinant baculoviruses containing gene 5 were selected and the
      protein was expressed to high yields in Spodoptera frugiperda cells. The
      recombinant protein was inoculated into rabbits and mice to produce specific
      hyperimmune antisera. The polyclonal antiserum reacted with a protein in
      rotavirus-infected MA104 cells and with a protein translated in vitro. This serum
      was also used to confirm that the gene 5 protein is not a structural protein.
      Recently, the gene 5 product has been predicted to be a zinc finger protein and
      reported to contain a highly conserved arrangement of cysteine residues; here, we
      demonstrate that the recombinant gene 5 protein binds zinc and is an RNA-binding
      protein as are several other zinc finger proteins.

PMID- 1379625
TI  - Neutralizing epitopes of the serotypes of bluetongue virus present in the United
      States.
AB  - Neutralizing epitopes present on the five serotypes of bluetongue virus (BTV)
      which have been isolated in the United States were investigated with a panel of
      monoclonal antibodies (MAbs). Neutralizing MAbs were raised against the U.S.
      prototype viruses of BTV serotypes 2, 10, 11, 13 and 17, and were reacted with
      each virus in both neutralization and immune precipitation assays. All MAbs
      neutralized and precipitated VP2 of the virus against which they were raised.
      Five MAbs raised against BTV-10 also precipitated VP2 of the prototype strain of
      BTV-17, and four of these MAbs neutralized BTV-17. To characterize further the
      neutralizing epitopes of BTV, the MAbs raised against BTV-10 and BTV-17 were
      reacted by immune precipitation and neutralization assays with four field strains
      each of BTV-17 and BTV-10 isolated from ruminants in the U.S. All MAbs raised
      against BTV-10 both precipitated VP2 and neutralized the four field isolates of
      BTV-10, whereas none of the MAbs raised against BTV-17 reacted with these
      viruses. By contrast, all seven MAbs raised against BTV-17 and four of the seven
      MAbs raised against BTV-10 precipitated VP2 of the four BTV-17 field isolates.
      Another MAb raised against BTV-10 precipitated VP2 of three of the four field
      isolates of BTV-17. Whereas neutralization of the BTV-17 field isolates by
      several MAbs was inconsistent, all 10 isolates of BTV-10 and BTV-17 were
      neutralized by three MAbs raised against BTV-10. Results of this and other
      studies indicate that multiple neutralizing epitopes exist on each serotype of
      BTV. Some of these epitopes are conserved whereas others apparently vary in their
      significance to the neutralization of individual field isolates of BTV-17 and
      perhaps other BTV serotypes. These findings have implications for the future
      development of efficacious subunit vaccines to prevent BTV infection of
      ruminants.

PMID- 1379626
TI  - The effects of a flanking sequence on the immune response to a B and a T cell
      epitope from the fusion protein of measles virus.
AB  - A region of the fusion protein of measles virus (residues 240 to 252) was
      predicted to contain a B and a T epitope. A synthetic peptide representing this
      sequence was shown to induce both T and B cell reactivity in several inbred
      strains of mice, but the responses were clearly major histocompatibility complex
      restricted. Elongation of this peptide by six residues at the C terminus on the
      basis of predictions for B cell epitopes resulted not only in increased peptide
      immunogenicity in some strains of mice but also produced strain-related positive
      and negative effects on the recognition of the peptide. BALB/c and SWR mice were
      non-responders to the short version of the peptide but responded well to the
      elongated form. On the other hand, the injection of the elongated peptide into
      C57BL/6 mice resulted in a loss of both B and T cell responsiveness seen with the
      short version. These results indicate the importance of flanking sequences on the
      immunogenicity and antigenicity of synthetic B and T cell epitopes and highlight
      the necessity to determine the most appropriate size of peptide to be used as an
      immunogen.

PMID- 1379627
TI  - Expression of the amino-terminal half of the NS1 region of the hepatitis C virus
      genome and detection of an antibody to the expressed protein in patients with
      liver diseases.
AB  - A cDNA fragment encompassing the 5'-terminal half of the NS1 region of the
      hepatitis C virus (HCV) genome was cloned. The cDNA was expressed in insect cells
      using a recombinant baculovirus, and a protein band of approximately 21K was
      identified by immunoblotting with a serum sample from a patient with chronic
      hepatitis C. Antibody to the protein was detected in sera from 13.4% of patients
      with chronic non-A, non-B hepatitis (NANBH), 20.8% of patients with liver
      cirrhosis and 16.8% of patients with hepatocellular carcinoma with no serum
      markers for hepatitis B virus infection. However, the antibody was not detected
      in sera from patients with acute NANBH. The prevalence of antibody to the protein
      encoded by the NS1 region was lower than that of antibody to the HCV core
      protein, but much higher than that of antibody to the envelope protein. Thus, the
      NS1 region of the HCV genome is suggested to encode a protein produced during the
      course of HCV replication.

PMID- 1379628
TI  - Modulatory role of glutathione on mu-opioid, substance P/neurokinin-1, and kainic
      acid receptor binding sites.
AB  - Reduced glutathione (L-gamma-glutamyl-L-cysteinylglycine; GSH) is an endogenous
      tripeptide involved in the formation and maintenance of protein thiol groups as
      well as in various detoxification reactions. Because multiple receptor types
      contain thiol groups or disulfide bridges, effects of GSH treatments on mu
      opioid, neurokinin-1/substance P, and kainic acid receptor binding sites were
      investigated and compared with those produced by dithiothreitol (DTT), a potent
      synthetic reducing agent. GSH inhibited binding more potently than did DTT at all
      three receptor types in porcine striatal membrane homogenates as well as in CHAPS
      solubilized preparations of the mu and neurokinin-1 sites. GSH-induced inhibitory
      effects were associated with decreases in maximal binding capacity (Bmax) without
      significant alteration in apparent affinity (KD). Cysteine, the functional moiety
      of GSH, mimicked GSH effects albeit with lower potencies, whereas oxidized
      glutathione had no effects at similar concentrations. In CHAPS-solubilized
      preparations, the combination of low concentrations of GSH and
      guanylylimidodiphosphate markedly decreased the Bmax values of the binding of
      [3H][D-Ala2,Gly-ol5]enkephalin and [3H]substance P. This GSH-mediated mechanism
      may be important to prevent cell overstimulation by accelerating receptor
      uncoupling, desensitization, and/or internalization. This is in keeping with
      purported roles of GSH related to the maintenance of cellular integrity.

PMID- 1379629
TI  - Hippocampal 8-[3H]hydroxy-2-(di-n-propylamino) tetralin binding site densities,
      serotonin receptor (5-HT1A) messenger ribonucleic acid abundance, and serotonin
      levels parallel the activity of the hypothalamopituitary-adrenal axis in rat.
AB  - We have previously demonstrated that susceptibility of the Lewis rat to
      inflammatory disease, compared with the relatively resistant Fischer F344/N rat,
      is related to a hyporesponsive hypothalamopituitary-adrenal axis to inflammatory
      and other stress mediators. Because serotonin (5-HT) and the 5-HT1A receptor are
      important stimulators of this axis, we have investigated the levels of 8-[3H]
      hydroxy-2,3-(di-n-propylamino)tetralin binding sites, 5-HT1A mRNA, 5-HT, and 5
      hydroxyindoleacetic acid in various brain regions of Lewis, outbred Harlan
      Sprague Dawley, and Fischer F344/N rats. Lewis rats expressed significantly fewer
      hippocampal and frontal cortical 8-[3H]-hydroxy-2,3-(di-n-propylamino)tetralin
      binding sites and less 5-HT1A mRNA than Harlan Sprague Dawley and Fischer F344/N
      rats. Adrenalectomy increased the number of 8-[3H]hydroxy-2,3-(di-n
      propylamino)tetralin binding sites and 5-HT1A mRNA expression in the hippocampus
      of all three strains. Levels of hippocampal 5-HT in Fischer F344/N rats were
      significantly greater than levels detected in the same regions from Lewis and
      Harlan Sprague Dawley rats. Hypothalamic 5-HT and 5-hydroxyindoleacetic acid
      levels in Harlan Sprague Dawley rats were higher than the same area from the
      other two strains. Adrenalectomy increased the levels of 5-hydroxyindoleacetic
      acid in the hypothalamus of all three strains. We conclude that hippocampal 5
      HT1A receptor densities and 5-HT levels in the rat parallel the activity and
      responsiveness of the hypothalamopituitary-adrenal axis.

PMID- 1379630
TI  - Simultaneous effects of p-chloroamphetamine, d-fenfluramine, and reserpine on
      free and stored 5-hydroxytryptamine in brain and blood.
AB  - The effects of acute treatment with p-chloramphetamine, d-fenfluramine, and
      reserpine on intracellular (brain tissue and whole blood) and extracellular (CSF
      and platelet-free plasma) compartments of 5-hydroxytryptamine (5-HT) in the brain
      and blood of the same rats have been examined. These treatments affected 5-HT in
      brain tissue and whole blood similarly (r = 0.823). Reserpine significantly
      reduced both intracellular pools at 2 and 24 h. p-Chloroamphetamine and d
      fenfluramine were more effective on brain tissue 5-HT. The concentration of 5-HT
      in CSF was significantly increased by all treatments. p-Chloroamphetamine induced
      a dramatic 70-fold increase of CSF 5-HT, paralleling a 42% decrease in brain
      tissue. d-Fenfluramine significantly increased CSF 5-HT to 212% of controls and
      reduced whole brain 5-HT (-23%). The effects of p-chloroamphetamine and d
      fenfluramine on 5-HIAA in brain, CSF, and plasma were nonsignificant. Individual
      values of 5-hydroxyindoleacetic acid (5-HIAA) in CSF and brain were highly
      correlated (r = 0.855), indicating that CSF 5-HIAA reflects well the
      concentration of 5-HIAA in brain tissue. Yet the intra- and extracellular
      concentrations of 5-HIAA were unrelated to the 5-HT changes. This indicates that
      CSF 5-HIAA does not reflect the active (extracellular) compartment of 5-HT in
      brain.

PMID- 1379631
TI  - Alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to human
      cerebral cortical membranes: minimal changes in postmortem brains of chronic
      schizophrenics.
AB  - The binding of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      ([3H]AMPA), a selective ligand for the ion channel-linked quisqualate receptor,
      was evaluated in Triton X-100-treated membranes of human cerebral cortex. The
      presence of chaotropic ions produced divergent effects on specific [3H]AMPA
      binding: A twofold increase in the binding was observed with thiocyanide at 100
      mM, although iodide (100 mM) and perchlorate (100 mM) reduced the binding.
      Chemical modifications of the sulfhydryl group with p-chloromercuriphenylsulfonic
      acid (PCMBS) produced threefold increases in specific [3H]-AMPA binding in the
      absence of KSCN as well as in the presence of KSCN. Treatment with dithiothreitol
      restored the enhanced specific [3H]AMPA binding by PCMBS to the basal level.
      Although specific [3H]AMPA binding in the absence of KSCN showed a single site
      (KD = 220 nM, Bmax = 235 fmol/mg of protein), curvilinear Scatchard plots of
      specific [3H]AMPA binding in the presence of 100 mM KSCN can be resolved into two
      binding sites with the following parameters: KD1 = 5.82 nM, Bmax1 = 247 fmol/mg
      of protein; KD2 = 214 nM, Bmax2 = 424 fmol/mg of protein. Quisqualate and AMPA
      were the most potent inhibitors of the [3H]AMPA binding in the presence of KSCN.
      Potent inhibitors of the binding included beta-N-oxalylamino-L-alanine (L-BOAA),
      cysteine-S-sulfate, L-glutamate, 6-cyano-7-nitroquinoxaline-2,3-dione, and 6,7
      dinitroquinoxaline-2,3-dione. Kainate, L-homocysteine sulfinic acid, and L
      homocysteic acid were active with an IC50 value of a micromolar concentration,
      whereas L-cysteic acid and L-cysteine sulfinic acid were weakly active.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1379632
TI  - Depolarization-dependent tyrosine phosphorylation in rat brain synaptosomes.
AB  - Synaptosomes from rat forebrain were analyzed for the presence of phosphotyrosine
      containing proteins by immunoblotting with antiphosphotyrosine antibodies. Using
      this technique, 10-11 phosphotyrosine-containing proteins were detected.
      Depolarization of synaptosomes by transfer to a high (41 mM) K+ medium resulted
      in increases in the phosphotyrosine content of several synaptosomal proteins, the
      most pronounced increase being associated with a membrane protein of M(r) 117,000
      (ptp117). Additional proteins exhibiting depolarization-dependent increases in
      phosphotyrosine content had molecular weights of 39,000, 104,000, 135,000, and
      160,000. The depolarization-dependent increase in the phosphotyrosine content of
      ptp117 was apparent within 30 s of the onset of depolarization, reached a maximum
      between 3 and 5 min, and then decreased to near control values by 30 min. The
      increase in tyrosine phosphorylation of ptp117 was dependent on the concentration
      of K+ in the depolarizing medium and was maximal with [K+] in excess of 50 mM. It
      was also calcium dependent and did not occur in the absence of extracellular
      calcium. The addition of veratridine to the incubation medium also resulted in an
      increase in the tyrosine phosphorylation of ptp117. The results suggest that the
      phosphorylation of synaptic proteins on tyrosine residues may be involved in the
      regulation or modulation of synaptic activity.

PMID- 1379633
TI  - Induction of nitric oxide synthase in glial cells.
AB  - Primary astrocyte cultures, C6 glioma cells, and N18 neuroblastoma cells were
      assayed for nitric oxide synthase (NOS) activity with a bioassay of cyclic GMP
      production in RFL-6 fibroblasts. Treatment of astrocyte cultures for 16-18 h with
      lipopolysaccharide (LPS) induced NOS-like activity that was L-arginine and NADPH
      dependent, Ca2+ independent, and potentiated by superoxide dismutase. Induction
      was evident after 4 h, was dependent on the dose of LPS, and required protein
      synthesis. Treatment of astrocyte cultures with leucine methyl ester reduced
      microglial cell contamination from 7 to 1%, with a loss of 44% of NOS-like
      activity. C6 cells treated with LPS also showed Ca(2+)-independent and L-arginine
      dependent NOS-like activity. N18 cells demonstrated constitutive Ca(2+)-dependent
      NOS-like activity that was not enhanced by LPS induction. These data indicate
      that NOS-like activity can be induced in microglia, astrocytes, and a related
      glioma cell line as it can in numerous other cell types, but not in neuron-like
      N18 cells.

PMID- 1379634
TI  - Desensitization of GABA-activated currents and channels in cultured cortical
      neurons.
AB  - Application of GABA to rat neocortical neurons maintained in cell culture
      produced a response that declined over several seconds, even in the continued
      presence of agonist. The decrement could be attributed to both a redistribution
      of Cl- and a true decline in GABA-induced membrane conductance, or
      desensitization. The extent and rate of desensitization were dose dependent in a
      manner similar to the dose dependence of the GABA-induced current, but were not
      related to the absolute magnitude of the current or to the charge transfer.
      Bicuculline slowed desensitization while diazepam enhanced the rate of
      desensitization, consistent with a localization of desensitization to the agonist
      receptor binding site. When measured in the whole-cell recording mode,
      desensitization was voltage dependent, becoming much slower as the membrane was
      depolarized. Changes in extracellular or intracellular [Ca2+] did not appear to
      grossly affect the desensitization process or its voltage dependence. GABA
      activated single channels, recorded in the outside-out configuration, also
      desensitized in the continued presence of agonist. However, desensitization
      differed from that seen in the same neurons in the whole-cell mode.
      Desensitization was considerably more rapid and did not show any voltage
      sensitivity. Moreover, single-channel responses often failed to recover after
      only a few exposures to agonist. Desensitization of GABA responses may play a
      role in the regulation of cortical inhibition, especially under conditions of
      intense excitatory and inhibitory synaptic activation.

PMID- 1379635
TI  - Robust enkephalin innervation of the locus coeruleus from the rostral medulla.
AB  - Substantial evidence indicates that the noradrenergic nucleus locus coeruleus
      (LC) is a key target of endogenous opioid neurons, and an important structure in
      mediating opiate effects. However, the detailed distribution of opioid fibers and
      terminals in the LC, and the sources of its opioid innervation are unknown. In
      the present study, the enkephalin innervation of the LC was investigated in the
      rat using an antibody directed against the extended enkephalin peptide Met
      enkephalin-Arg6-Gly7-Leu8 (ENK), which is derived exclusively from the enkephalin
      precursor proenkephalin A. An antibody directed against tyrosine hydroxylase
      (TH), the synthetic enzyme for catecholaminergic neurons, was also applied to the
      same tissue sections to delineate LC neurons and their dendrites. Enkephalin
      fibers in the LC were dense and highly varicose. In horizontal sections, ENK-like
      immunoreactive (ENK-ir) fibers of considerable length coursed throughout the
      rostrocaudal orientation of the LC proper, whereas in frontal sections ENK-ir
      processes appeared punctate, suggesting a rostrocaudal orientation. Dense ENK-ir
      fibers were also identified in the rostromedial and caudal juxtaependymal
      pericoerulear regions where extranuclear dendrites of LC neurons are extensive.
      As previously reported, there were no ENK-ir neurons in the LC nucleus proper,
      but such cells were present in neighboring structures such as the parabrachial,
      sphenoid, and Barrington's nuclei as well as in the central gray and in the
      subcoeruleus area. ENK-ir neurons were also present in nuclei of the rostral
      medulla reported to be major afferents of the LC, the nucleus prepositus
      hypoglossi (PrH), and the nucleus paragigantocellularis (PGi). In the dorsomedial
      medulla, numerous ENK-ir neurons were identified in the medial aspect of the PrH
      and along the medial longitudinal fasciculus in the perifascicular reticular
      formation. In the ventrolateral medulla, ENK-ir neurons were distributed in a
      conical caudorostral column throughout the PGi. Retrograde transport of a WGA
      colloidal gold conjugate (WGA-apoHRP-Au) from LC, combined with
      immunohistochemistry for ENK in the same tissue sections, revealed that LC
      afferents in the PGi and PrH were interdigitated with ENK-ir neurons.
      Furthermore, an unexpectedly high incidence of doubly labeled neurons were
      identified in both PGi and PrH. Overall, 57% and 56% of the LC-projecting neurons
      in PGi and PrH, respectively, were also immunoreactive for ENK, suggesting that
      enkephalinergic neurons of PGi and PrH are major afferents to noradrenergic LC
      neurons.

PMID- 1379636
TI  - Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure,
      and functional expression.
AB  - Phototransduction in retinal rods involves a G-protein-mediated signaling cascade
      that leads to cGMP hydrolysis and the closure of a cGMP-gated channel. This
      channel has recently been purified from bovine retina and molecularly cloned
      (Kaupp et al., 1989). We report here the cloning of cDNA and genomic DNA encoding
      the human rod cGMP-gated channel, based upon its homology to the bovine
      counterpart. The human mRNA structure differs from the bovine in containing an
      Alu repetitive element spliced into the 5' untranslated region. The human cGMP
      gated channel gene (CNCG) is located on chromosome 4 and contains at least 10
      exons. One large exon encodes the carboxy-terminal two-thirds of the protein,
      whereas seven small exons encode the amino-terminal one-third of the protein.
      Alternative splicing removes one of the small exons in a subset of transcripts in
      the human retina, producing an internal in-frame deletion of 36 codons. When
      expressed in a human embryonic kidney cell line (293S), the full-length cDNA
      clone, but not the differentially spliced variant, produced functional ion
      channels broadly similar to the native channels in vertebrate rods.

PMID- 1379637
TI  - Clinical profile of apparently healthy neonates with in utero drug exposure.
AB  - OBJECTIVE: To identify the characteristics of neonates exposed to drugs in utero
      but admitted to the normal newborn nursery because of apparent good health.
      DESIGN: Retrospective evaluation with chart review of toxicology screening tests
      sent from a normal newborn nursery. SETTING: Newborn service in an urban
      hospital. PARTICIPANTS: Fifty newborns with positive drug screening results. MAIN
      OUTCOMES: Frequency of positive results and assessment of demographic features
      and neonates' clinical features. RESULTS: 43 (86%) of the apparently healthy
      newborns tested positive for cocaine. The results of simultaneous or proximate
      drug testing of mothers and their newborns were discordant in 11 (22%) cases.
      CONCLUSIONS: Neonates with in utero drug exposure often are born with few or no
      signs of abnormality and are admitted to the normal newborn nursery.

PMID- 1379638
TI  - Antitumor agents. 134. New shiraiachrome-A- and calphostin-C-related perylene
      derivatives as cytotoxic and antiviral agents and inhibitors of protein kinase C.
AB  - Shiraiachrome-A and -B have been isolated from the mycelium of the Chinese bamboo
      fungus Shiraia bambusicola as the cytotoxic principles. A series of new perylene
      derivatives (7-27) related to Shiraiachrome-A and -B as well as Calphostin-C have
      been synthesized and evaluated for their cytotoxicity, antiviral activity, and
      inhibitory activity against protein kinase C. The results indicated that 11 and
      12 are potent cytotoxic agents against HCT-8, RPMI-7951, and TE-671 solid tumor
      cells, whereas 24 and 26 demonstrated strong antiviral activity against HSV-1 and
      HSV-2. Compound 10 is an inhibitor of protein kinase C.

PMID- 1379639
TI  - The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the
      tropical rainforest tree, Calophyllum lanigerum.
AB  - Eight new coumarin compounds (1-8) were isolated by anti-HIV bioassay-guided
      fractionation of an extract of Calophyllum lanigerum. The structures of
      calanolide A (1), 12-acetoxycalanolide A (2), 12-methoxycalanolide A (3),
      calanolide B (4), 12-methoxycalanolide B (5), calanolide C (6) and related
      derivatives 7 and 8 were solved by extensive spectroscopic analyses, particularly
      HMQC, HMBC, and difference NOE NMR experiments. The absolute stereochemistry of
      calanolide A (1) and calanolide B (4) was established by a modified Mosher's
      method. Calanolides A (1) and B (4) were completely protective against HIV-1
      replication and cytopathicity (EC50 values of 0.1 microM and 0.4 microM,
      respectively), but were inactive against HIV-2. Some of the related compounds
      also showed evidence of anti-HIV-1 activity. Studies with purified bacterial
      recombinant reverse transcriptases (RT) revealed that the calanolides are HIV-1
      specific RT inhibitors. Moreover, calanolide A was active not only against the
      AZT-resistant G-9106 strain of HIV-1 but also against the pyridinone-resistant
      A17 strain. This was of particular interest since the A17 virus is highly
      resistant to previously known HIV-1 specific, non-nucleoside RT inhibitors (e.g.,
      TIBO; BI-RG-587; L693,593) which comprise a structurally diverse but apparently
      common pharmacologic class. The calanolides represent a substantial departure
      from the known class and therefore provide a novel new anti-HIV chemotype for
      drug development.

PMID- 1379640
TI  - Amide, urea, and carbamate analogues of the muscarinic agent [4-[[N-(3
      chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride.
AB  - A series of amide, urea, and carbamate analogues of the muscarinic (M1)
      ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2
      butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl
      substituted carbamates 8-11 were resolved into the enantiomers. In order to
      investigate the ganglionic stimulant activity and affinity of the new compounds
      we studied their ability to increase mean arterial blood pressure (MAP) in the
      pithed rat and their ability to displace the M1 receptor selective antagonist
      [3H]pirenzepine from rabbit sympathetic ganglia. The quaternary ammonium
      derivatives of 1, but not their corresponding tertiary amines, displayed
      ganglionic stimulant properties. The urea derivative 14 and the acetamide
      derivative 18 were almost equipotent to 1 as ganglionic agonists. In addition, 14
      and 18 showed only 2- to 3-fold less affinity to ganglionic muscarinic receptors
      than 1. Introduction of a methyl group in the 1 position of the butynyl chain of
      1 and its 4-chlorophenyl analogue increased ganglionic stimulant potency. The
      resulting (+/-)-9 and (+/-)-11 were the most potent analogues in this study. They
      were found to be partial agonists and showed 5- and 16-fold higher potency than
      1, respectively, in increasing the MAP. They also displayed 6- and 18-fold higher
      affinity than 1 for ganglionic M1 receptors. The (S)-enantiomers of 9 and 11 were
      1.5- and 4.9-fold more potent, respectively, than their antipodes as ganglionic
      muscarinic stimulants. The C1-methyl-substituted urea and acetamide derivatives
      (15 and 19) were 1.5- and 3-fold less potent than 1 and displayed several-fold
      lower affinity for ganglionic M1 receptors. The new quaternary analogues retained
      the selectivity for ganglionic muscarinic receptors since they produced weak
      partial agonist effects on the guinea pig ileum and showed several-fold lower
      nicotinic activity than 1 in the frog rectus abdominis assay.

PMID- 1379641
TI  - Structural requirements for neuropeptide Y18-36-evoked hypotension: a systematic
      study.
AB  - It has been shown that NPY and select C-terminal fragments of NPY that evoke a
      hypotensive response upon intraarterial administration in the rat also cause mast
      cell degranulation and histamine release in vitro. Additionally, elevation of
      plasma histamine levels has been observed concomitant with the hypotensive effect
      of NPY and various C-terminal fragments. In order to investigate whether the
      hypotensive response to NPY18-36 is correlated to this observed elevation of
      histamine in vivo, we sought to characterize the structural requirements for each
      activity. We conducted a systematic replacement of each amino acid in NPY18-36 by
      its D-isomer. Additionally, various modifications were made to the N- or C
      terminii of NPY18-36. The following rank order of potency was obtained for the
      hypotensive action of these analogues of NPY18-36 relative to NPY18-36. Only one
      analogue ([D-Tyr21]NPY18-36) exhibited significantly enhanced potency. Eleven
      analogues of NPY18-36, ([D-Thr32]-, [D-Arg35]-, [D-Ile31]-, [D-Leu30]-, [D-Tyr27]
      , [D-Ser22]-, [D-Tyr36]-, [D-Gln34]-, [D-Asn29]-, [D-Ala23]-, and [D-Arg33]NPY18
      36) were equipotent with NPY18-36. Four analogues ([D-His26]-, [D-Ile28]-, and [D
      Ala18]NPY18-36 and -NPY18-27) had reduced potency (10-80%) while eight analogues
      ([D-Arg19]-, [D-Tyr20], [D-Leu24]-, [D-Arg25]-, [Ac-Ala18]-, [Me-Ala18]-,
      [desamino-Ala18]NPY18-36 and NPY18-36 free acid) failed to produce a significant
      hypotensive response (less than 10%) at the doses tested. The sensitivity of
      NPY18-36 to chiral inversion of single residues or other modifications at the N
      terminus suggested the presence of a conformationally well defined N-terminal
      pharmacophore. Additionally, five NPY18-36 analogues were tested for elevation of
      plasma histamine levels. The rank order of potency ([D-Thr32]NPY18-36 = [D
      Tyr21]NPY18-36 much greater than NPY18-36 greater than [D-Ala18]NPY18-36 greater
      than [Ac-Ala18]NPY18-36) was correlated with each analogue's potency at evoking a
      hypotensive response. In contrast, NPY1-36 failed to evoke an elevation in plasma
      histamine levels despite its hypotensive effects. Hence, we conclude that the
      magnitude of the hypotensive response evoked by an NPY18-36 analogue is primarily
      a function of its ability to elevate plasma histamine levels. However, the
      mechanism underlying NPY1-36-evoked hypotension appears to be different.

PMID- 1379642
TI  - Mitochondrial transfer RNA genes in a black fly, Simulium vittatum (Diptera:
      Simuliidae), indicate long divergence from mosquito (Diptera: Culicidae) and
      fruit fly (Diptera: Drosophilidae).
AB  - Sequences are given for nine complete genes and one partial mitochondrial tRNA
      gene of the black fly, Simulium vittatum (Zetterstedt). Sequenced tRNA genes were
      for alanine, arginine, asparagine, aspartic acid, glutamic acid, glycine,
      leucine(CUN), lysine, serine(AGN), and valine. Nucleotides were aligned with the
      same previously sequenced genes in Aedes albopictus Skuse and Drosophila yakuba
      Burla. A cluster of six tRNA genes, which differ in arrangement in Ae. albopictus
      and D. yakuba, was amplified by PCR and found to have the same position and
      orientation in S. vittatum as in D. yakuba. Overall, similarity with either D.
      yakuba or Ae. albopictus was 86%. Sequences that were common to the three insects
      suggest that black flies and mosquitoes are as divergent from each other as
      either is from Drosophila. Sequences for nine species of black flies were
      obtained for tRNA leucine(CUN) from DNA amplified with another primer set. Little
      variation occurred within the tRNA gene but, by including the flanking regions to
      provide 175 base pairs, a phylogeny of the nine species was obtained that was
      largely consistent with current classification.

PMID- 1379643
TI  - IP3- and cAMP-induced responses in isolated olfactory receptor neurons from the
      channel catfish.
AB  - Olfactory receptor neurons enzymatically dissociated from channel catfish
      olfactory epithelium were depolarized transiently following dialysis of IP3 or
      cAMP (added to the patch pipette) into the cytoplasm. Voltage and current
      responses to IP3 were blocked by ruthenium red, a blocker of an IP3-gated Ca(2+)
      release channel in sarcoplasmic reticulum. In contrast, the responses to cAMP
      were not blocked by extracellularly applied ruthenium red, nor by L-cis-diltiazem
      or amiloride and two of its derivatives. The current elicited by cytoplasmic IP3
      in neurons under voltage clamp displayed a voltage dependence different from that
      of the cAMP response which showed marked outward rectification. A sustained
      depolarization was caused by increased cytoplasmic IP3 or cAMP when the buffering
      capacity for Ca2+ of the pipette solution was increased, when extracellular Ca2+
      was removed or after addition of 20-200 nM charybdotoxin to the bathing solution,
      indicating that the repolarization was caused by an increase in [Cai] that opened
      Ca(2+)-activated K+ channels. The results suggest that different conductances
      modulated by either IP3 or cAMP are involved in mediating olfactory transduction
      in catfish olfactory receptor neurons and that Ca(2+)-activated K+ channels
      contribute to the termination of the IP3 and cAMP responses.

PMID- 1379644
TI  - Differential sensitivity of pneumolysin-induced channels to gating by divalent
      cations.
AB  - The induction of channels across planar lipid bilayers by purified, recombinant
      pneumolysin (a hemolytic protein from Streptococcus pneumoniae) has been studied
      by measuring increases in electrical conductivity. Pneumolysin-induced channels
      exhibit a wide range of single channel conductances (less than 50 pS to greater
      than 1 nS at 0.1 M KCl). Channels can be categorized on the basis of their K+:Cl-
      selectivity: the smallest channels are strongly cation selective, with t+ (the
      cation transference number) approaching 1.0; the largest channels are unselective
      (t+ approximately 0.5). Channels tend to remain open at all voltages (-150 to 150
      mV); only the smallest channels exhibit any rectification. In the presence of
      divalent cations (1-5 mM Zn2+; 10-20 mM Ca2+), small (less than 50 pS) and medium
      sized (50 pS to 1 nS) channels are closed in a voltage-dependent manner (more
      closure at higher voltages); at 0 voltage channels reopen. Overall selectivity is
      reduced by divalent cations, compatible with small, selective channels being
      closed preferentially to large, nonselective ones. It is concluded that a single
      molecular species (pneumolysin) induces multiple-sized channels that can be
      categorized by cation:anion selectivity and by their sensitivity to closure by
      divalent cations.

PMID- 1379645
TI  - Regulation of insulin-like growth factor-binding protein (IGFBP) expression by
      breast cancer cells: use of IGFBP-1 as an inhibitor of insulin-like growth factor
      action.
AB  - BACKGROUND: The insulin-like growth factors (IGFs) play an important role in
      normal growth and development. Evidence suggests they may also regulate the
      growth of several cancer cell types. This regulation is mediated by interactions
      between the receptors and ligands. There is now ample evidence to suggest that
      these interactions are also influenced by extracellular IGF-binding proteins
      (IGFBPs). Six different IGFBPs have been cloned. Some species may act to inhibit
      the mitogenic effects of the IGFs. Since breast cancer cells are responsive to
      the IGFs, it is possible that regulated expression of the IGFBPs affects tumor
      growth. Furthermore, inhibitory binding proteins could be used as neutralizers of
      IGF action. PURPOSE: We conducted this study to fully characterize the expression
      and hormonal regulation of IGF-binding protein expression in human MCF-7 breast
      cancer cells and to test the ability of purified IGFBP-1 to inhibit IGF-I action.
      METHODS: We used ribonuclease protection assays and Western ligand blotting to
      examine IGFBP expression in MCF-7 cells. The effect of IGF-I, IGFBP-1, and 17
      beta-estradiol on serum-free cell growth was also studied. RESULTS: MCF-7 cells
      expressed IGFBP-2, IGFBP-4, and IGFBP-5 RNA and protein. These cells are
      dependent on estrogen for growth. In short-term culture, IGF-I can substitute for
      estrogen. Concomitant addition of IGF-I and estrogen enhanced stimulation above
      the level achieved by either factor alone. Estrogen also increased IGFBP
      production, making it unlikely that the IGFBPs induced by estrogen in MCF-7 cells
      could function as major inhibitors of IGF action. In contrast, exogenous addition
      of IGFBP-1 could block IGF-I-induced mitogenesis; this effect was reversible by
      excess IGF-I. CONCLUSIONS: The studies suggest that cancer cell growth may be
      regulated by endogenous IGFBP expression. Furthermore, the exogenous addition of
      the IGFBP-1 blocked IGF-I action and potentially could be used as a pharmacologic
      inhibitor of IGF action.

PMID- 1379646
TI  - Enhanced angiogenesis and growth of collaterals by in vivo administration of
      recombinant basic fibroblast growth factor in a rabbit model of acute lower limb
      ischemia: dose-response effect of basic fibroblast growth factor.
AB  - The purpose of this study was to evaluate the effects of exogenous recombinant
      basic fibroblast growth factor (bFGF) on angiogenesis in severely ischemic tissue
      beds. We used a two-stage procedure to produce severe ischemia of the hindlimb of
      34 New Zealand rabbits. The ischemic hindlimb received intramuscular injection of
      saline (group A), 1 microgram bFGF (group B), or 3 micrograms bFGF (group C),
      daily for 2 weeks. Tissue perfusion, skeletal muscle infarction, angiogenesis,
      and collateral growth were assessed by angiography, transcutaneous oximetry
      (TcPO2), quantitative spectrophotometric assay of triphenyltetrazolium chloride
      reduction in muscle, capillary density (capillaries per square millimeter), and
      capillary per muscle fiber ratio. There were no significant differences in
      baseline TcPO2 among the three groups for both thigh and calf measurements.
      Angiography revealed extensive perfusion of the left hindlimb in all the assessed
      bFGF treated animals. Both thigh and calf TcPO2 values showed a significant
      increase in all groups over the 14 days ischemia was induced (p less than
      0.0001), but the two treatment groups exhibited a much more rapid rise in TcPO2
      than the control group (p less than 0.0001). The capillaries per square
      millimeter and capillaries per muscle fiber ratios were significantly increased
      in all posttreatment measurements for all animals that received bFGF. The
      treatment groups with bFGF had a significant (p = 0.025) increase in thigh muscle
      viability compared with controls based on triphenyltetrazolium chloride
      reduction. Whereas there was evidence of muscle infarction in both the thighs of
      groups A and B, there was none in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379647
TI  - The value and limitation of iloprost infusion in decreasing skeletal muscle
      necrosis.
AB  - Iloprost has been shown to minimize skeletal muscle necrosis when administered
      before the onset of ischemia in animal experiments, possibly by preventing
      neutrophil activation. Since patients with acute limb ischemia are seen after the
      process has begun, we investigated whether iloprost can be protective when given
      only during reperfusion. After anesthesia, 18 adult mongrel dogs underwent a
      standard isolated gracilis muscle preparation. In six control animals (group I)
      the gracilis muscle was subjected to 6 hours of ischemia followed by 48 hours of
      reperfusion. Group II animals (n = 6) received intravenous infusion of iloprost
      at a dose of 0.45 microgram/kg/hr beginning 1 hour before the onset of muscle
      ischemia and throughout the experiment (6 hours of ischemia and 1 hour of
      reperfusion). In addition to the continuous infusion, they received 0.45
      microgram/kg intravenous boluses of iloprost 10 minutes before the induction of
      ischemia and 10 minutes before reperfusion. Group III animals (n = 6) had a
      similar ischemic interval, but were given a bolus of iloprost of 0.45
      microgram/kg at end ischemia followed by continuous infusion of 0.45
      microgram/kg/hr for 48 hours during reperfusion. Muscle biopsies were obtained at
      baseline and after 1 hour of reperfusion in all groups. Additional biopsies were
      obtained at 48 hours of reperfusion in groups I and III. Myeloperoxidase
      activity, a marker of neutrophil activation, was measured in all muscle biopsies.
      At the end of reperfusion, the gracilis muscle was harvested in all animals and
      weighed. Muscle necrosis was estimated by serial transection, nitroblue
      tetrazolium histochemical staining followed by computerized planimetry.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1379648
TI  - Serial cultivation of adult human endothelium from the great saphenous vein.
AB  - The growth of endothelial cells from small segments of human great saphenous vein
      was investigated for possible functional studies of endothelial cell properties
      and endothelialization of cardiovascular prosthetic graft materials. Growth in
      medium containing fetal calf serum or human serum was compared, and the effects
      of adding compounds that increase intracellular cyclic adenosine monophosphate
      levels, that is, cholera toxin and isobutylmethylxanthine, were also examined. It
      was shown that human serum was more efficient in stimulating cell growth than
      fetal calf serum at all concentrations tested. It was also shown that the
      addition of cholera toxin and isobutylmethylxanthine significantly potentiated
      growth. Minimal Essential Medium with the addition of 40% human serum and cholera
      toxin (1 nmol/L) and isobutylmethylxanthine (33 mumol/L) was shown to be optimal.
      From a single segment (3 to 5 cm), 20 x 10(6) human saphenous vein endothelial
      cells corresponding to 2000 cm2 or more could be achieved after 3 to 4 weeks in
      culture. The human saphenous vein endothelial cell cultures retained their
      cobblestone appearance, expression of von Willebrand Factor (vWF)-antigen, and
      capacity for prostacyclin production after six passages. We suggest that this
      provides a practically useful method for studies of cultured endothelium and
      possibly for pre-endothelialization of cardiovascular prosthetic materials.

PMID- 1379649
TI  - [Combination effect of KW-2228 and cephem antibiotics in a systemic infection
      model in neutropenic mice].
AB  - A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW
      2228, has some excellent properties such as high specific activity in stimulating
      granulocyte colony-formation in vitro, great biological stability in plasma, good
      pharmacokinetic profile and high potency in granulopoiesis in normal mice in
      vivo. Recently, the application of G-CSF against infectious diseases has been
      considered, and some animal experiments have been carried out to support its
      clinical applications. In this paper, we investigated protective effects of KW
      2228 against systemic infections caused by Klebsiella pneumoniae in mice with
      leukopenia induced by the administration of cyclophosphamide. KW-2228 (1
      microgram/mouse) was administered (s.c.) once a day for 4 days following
      cyclophosphamide administration, then mice were challenged with K. pneumoniae
      (i.p.) 4 hours after the last administration of KW-2228. An antibiotic was
      administered (s.c., p.o.) 2 hours after the bacterial challenge. Combination
      effects of KW-2228 with cefazoline, cefmetazole, ceftazidime or cefaclor were
      evaluated in the systemic infection with K. pneumoniae. Each combination therapy
      using KW-2228 with each of the cephems exhibited an excellent protective effect
      in comparison to the therapy with a cephem alone. These results show the
      possibility that KW-2228 could be of use in treating obstinate infections not
      successfully treated with an antimicrobial agent alone.

PMID- 1379651
TI  - [Protective effect of KW-2228 in a systemic infection model of CPA-treated tumor
      bearing mice].
AB  - A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW
      2228, has some excellent properties such as high specific activity in stimulating
      granulocyte colony-formation in vitro, great biological stability in plasma, good
      pharmacokinetic profile and high potency in granulopoiesis in normal mice in
      vivo. Recently, the application of G-CSF against infectious diseases has been
      considered, and some animal experiments have been carried out to support its in
      clinical applications. Patients with underlying diseases such as leukemia or
      cancer often have recurrent infections because of reduced number and functions of
      neutrophils, which mediate an early stage of host defense. We investigated the
      prophylactic effect of KW-2228 against an experimental systemic infection with
      Pseudomonas aeruginosa in tumor-bearing mice (colon 26: BALB/c) treated with
      cyclophosphamide. KW-2228 (0.25-2.0 micrograms/mouse) was administered (s.c.)
      once a day for 4 days before the experimental bacterial infection. As a result of
      KW-2228 administration, the reduction in peripheral blood neutrophils usually
      caused by the injection with cyclophosphamide was prevented markedly. KW-2228
      displayed excellent protective potency dose-dependently against the infection
      with P. aeruginosa in tumor-bearing mice. These data show the possibility that
      prophylactic therapy with KW-2228 may augment the host defense of
      immunocompromised patients to infections. It present, clinical efficacy studies
      on KW-2228 are under way.

PMID- 1379650
TI  - [Effects of KW-2228 on the function of polymorphonuclear neutrophils in rats for
      the phagocytosis and killing activity and the production of active oxygen].
AB  - KW-2228 is a novel derivative of a recombinant human granulocyte colony
      stimulating factor (rhG-CSF) with a modification. KW-2228 has some excellent
      properties such as high specific activity in stimulating granulocyte colony
      formation in vitro, great biological stability in plasma, good pharmacokinetic
      profile and high potency in granulopoiesis in normal mice in vivo. In the present
      study, we investigated the effect of KW-2228 on phagocytic capacity and killing
      action of polymorphonuclear neutrophils (PMNs) obtained from normal rats which
      had been treated with KW-2228 using various microorganisms, such as Candida
      albicans, Escherichia coli and Pseudomonas aeruginosa. We also investigated the
      effect of KW-2228 on the production of superoxide anion using a luminol
      chemiluminescence method. KW-2228 enhanced the phagocytosis and killing activity
      of PMNs of rats against C. albicans and E. coli. PMNs treated with KW-2228 showed
      some bactericidal activity against P. aeruginosa. These data obtained with PMNs
      treated with KW-2228 show a correlation between the bacterial susceptibility to
      phagocytosis and killing action and the lunimol-dependent chemiluminescence
      response. These results suggest the significance and the efficacy of KW-2228 used
      in an additional therapy to that of antibiotics in the treatment of infections
      diseases. KW-2228 is currently in Phase III clinical trials in Japan.

PMID- 1379652
TI  - [Combination effects between KW-2228 and antibiotics against systemic infections
      in normal and neutropenic mice].
AB  - KW-2228, a mutationally modified recombinant human granulocyte colony-stimulating
      factor (rhG-CSF), possesses some excellent properties such as high specific
      activity in stimulating granulocyte colony-formation in vitro, great biological
      stability in plasma, good pharmacokinetic profile and high potency in
      granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against
      infectious diseases has been considered, and some animal experiments have been
      carried out to support such an application on human infectious diseases. In this
      paper, we examined combination effect of KW-2228 with various chemotherapeutic
      drugs in experimental infectious in mice. A combination effect of KW-2228 with
      ceftazidime (CAZ) was evaluated in a systemic infection with Pseudomonas
      aeruginosa in normal mice. Combination effects of KW-2228 with CAZ, astromicin
      and amphotericin B were also evaluated in experimental systemic infections caused
      by P. aeruginosa, Serratia marcescens and Candida albicans in immunosuppressed
      mice treated with cyclophosphamide. Synergistic effects were generally observed
      at KW-2228 doses from 1 to 5 micrograms per mouse with all combinations. We
      concluded that combination therapies of KW-2228 with various chemotherapeutic
      drugs in experimental infections in mice showed that it should be effective in
      normal and immunosuppressed host. These results of our laboratory studies suggest
      that KW-2228 in combination with antibiotics would be useful in the clinical
      treatment of microbial infections. Recently, clinical efficacy studies of KW-2228
      have been initiated in Japan.

PMID- 1379653
TI  - [Combination effect of KW-2228 and aminoglycoside antibiotics on systemic
      infection in cyclophosphamide-treated tumor-bearing mice].
AB  - A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW
      2228, has some excellent properties such as high specific activity in stimulating
      granulocyte colony-formation in vitro, great biological stability in plasma, good
      pharmacokinetic profile and high potency in granulopoiesis in normal mice in
      vivo. Recently, the application of G-CSF against infectious diseases has been
      considered, and some animal experiments have been carried out to support its
      clinical applications. Patients with underlying diseases such as leukemia and
      cancer often have recurrent infections because of reduced numbers or functions of
      neutrophils, which mediate an early stage of host defense. In out present study,
      we established a new method to evaluate in vivo potency of G-CSF in colon 26
      tumor-bearing mice. By using the method, we examined combination effects of KW
      2228 with aminoglycoside antibiotics against a systemic infection caused by
      Pseudomonas aeruginosa. KW-2228 (1 microgram/mouse/day) was administered (s.c.)
      once a day for 4 days before the bacterial infection was introduced in colon 26
      tumor-bearing mice receiving cyclophosphamide 3 days after the transplantation of
      tumor. Antibiotics were administered (s.c.) 2 hours after the introduction of the
      bacterial infection. ED50 of gentamicin (GM) alone and that of the combination
      with KW-2228 were 40.7 mg/kg and 3.6 mg/kg, respectively. ED50 of astromicin
      (ASTM) alone and that of the combination with KW-2228 were 386 mg/kg and 17.8
      mg/kg, respectively. Thus the combination therapy of KW-2228 with GM or ASTM
      exhibited excellent protective effects in comparison to the treatment with
      antibiotic alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379655
TI  - [The effect of intra-urethral catheter for prostatic hypertrophy patients who are
      unfit for operation and suffer from urinary retention].
AB  - The effect of double Malecot type polyurethane intraurethral catheter (IUC) was
      examined in 17 benign prostatic hypertrophy patients who were unfit for operation
      and suffered from urinary retention. Patients were aged 68 to 90 (mean 80.5)
      years old and the causes of IUC insertion were cardiac, cerebrovascular,
      respiratory and gastrointestinal diseases, diabetes mellitus and aging. IUC was
      selected among three types (55, 60, 65 mm) according to the length of prostatic
      urethra. Insertion of IUC was carried out easily under fluoroscopic guidance
      without endoscopy. All patients could void by themselves just after insertion of
      IUC and the longest indwelling period was 10 months. The length of IUC need not
      be longer than that of prostatic urethra and patients with normal or hypertonic
      bladder could void better than those with atonic bladder. Urinary tract infection
      did not get worse in any patients with indwelling IUC. Double Malecot type
      polyurethane IUC is a safe and an effective alternative method in place of
      urethral balloon catheter for inoperable prostatic hypertrophy patients in
      urinary retention.

PMID- 1379654
TI  - [Basic and clinical studies of local hyperthermia for prostatic cancer].
AB  - The effect of local hyperthermia on the prostate using 13.56 MHz radio frequency
      wave (RF wave) was reported. Firstly, temperature and blood flow of the prostate
      in normal dogs were measured during local hyperthermia. In most part of the
      prostate, the temperature reached over 42 degrees C, which was considered as
      favorable for the hyperthermia therapy. Blood flow of the prostatic tissue rose
      more slowly than that of muscle tissue. Secondly, the tissue concentration of
      anticancer agents after local hyperthermia was measured. There was a tendency
      that drug concentration in the prostate tissue after local hyperthermia was
      higher than that without local hyperthermia. Histological findings showed
      interstitial edema and congestion. As a clinical trial, 14 cases of prostatic
      cancer were treated with local hyperthermia after the administration of
      anticancer agents. Seven of them were fresh cases and the others were relapsed
      cases. After treatment, tumor size was reduced in 13 cases. According to "The
      Response Criteria for Urologic Tumor", one Complete Response, 3 Partial Response
      and 10 No Change cases were obtained. There was no tumor progression. As for side
      effects, bone marrow suppression, loss of appetite, diarrhea and skin burns were
      noted. However, these side effects were mild, and did not interrupt the
      treatment. Local hyperthermia of the prostate after systemic chemotherapy could
      be carried out safely and effectively in patients with prostatic cancer.

PMID- 1379656
TI  - [Adjuvant chemotherapy (MVP-CAB; methotrexate, vincristine, cisplatinum,
      cyclophosphamide, adriamycin, and bleomycin) for bladder cancer].
AB  - Twenty-three patients with bladder cancer (TCC; 18 patients, SCC; 5 patients)
      were treated with adjuvant chemotherapy (day 1: methotrexate 20 mg/m2,
      vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, bleomycin
      30 mg, day 2: cisplatinum 50 mg/m2; MVP-CAB). A total of 3 cycles of MVP-CAB were
      given as preoperative or postoperative therapy. The following results were
      obtained. Group 1 (purpose to preserve the bladder, preoperative MVP-CAB): Four
      of 7 patients achieved a partial response. It was possible to perform bladder
      preservation surgery in 3 of these 4 patients. All 3 patients had pedunculated,
      solitary tumors, and there was no carcinoma in situ. Group 2 (purpose to improve
      the prognosis; preoperative MVP-CAB): Hydronephrosis did not resolve in the 4
      patients with this complication. They received total cystectomy, and 2 patients
      died of cancer 23 months later. Group 3 (purpose to improve the prognosis;
      postoperative MVP-CAB): Ten of 12 patients (total cystectomy; 10 patients,
      partial cystectomy; 2 patients) survived disease-free for an average of 17 months
      (5-44 months), 1 patient developed recurrence 12 months later, and 1 patient died
      of cancer 6 months later. The 1-year survival rate in Group 3 was 86% for TCC,
      100% for SCC, 80% for grade 3 TCC, and 89% for pT2 or more advanced cancer.

PMID- 1379657
TI  - [Functional and morphological changes in rat kidney induced by FK506 and its
      reversal by various vasodilators].
AB  - FK506, a newly developed immunosuppressive agent, has recently been used for
      human liver and kidney transplantation. The present study was carried out to
      assess the functional and morphological changes by acute or chronic
      administration of FK506 in heminephrectomized rats. FK506 was given intravenously
      at the dose of 0.384 mg/kg/hr for 90 min in acute experiment. FK506 was
      administered by gastric gavage at doses of 1, 2.5, 5 mg/kg for 21 days. Blood and
      urinary biochemistry were monitored every week. Inulin and PAH clearance studies
      were conducted during the infusion of FK506 for acute study, and at day 21 for
      chronic study. Some of the rats were treated with diltiazem (Dilt), captopril or
      prazosine for 21 days to prevent FK506 nephrotoxicity. Acute infusion of FK506
      did not change renal and systemic hemodynamics. Creatinine clearance showed a
      dose dependent decrease by 10-20% in the rats with chronic administration of
      FK506. Inulin/PAH clearance indicated a decrease in glomerular filtration rate
      and renal plasma flow with an increase in renal vascular resistance. The renal
      histology showed vacuolization in proximal tubuli and media of smooth muscle
      cells of arterioles. The administration of Dilt functionally and morphologically
      improved renal impairment induced by FK506. In conclusion, FK506 induces a dose
      dependent decrease in renal function with significant histological changes in
      tubuli and arterioles in rat kidney. Intracellular calcium deregulation seems to
      be involved in FK506-induced nephrotoxicity.

PMID- 1379658
TI  - [Endocrine environment of benign prostatic hyperplasia--relationships of sex
      steroid hormone levels with age and the size of the prostate].
AB  - To determine the influence of endocrine factors on benign prostatic hyperplasia
      (BHP), the levels of three sex steroid hormones i.e., total testosterone (Total
      T), free testosterone (Free-T) and estradiol (E2), were measured in serum of
      healthy 154 men. Their ages ranged from 18 to 91 years old. In 59 men, prostatic
      size was estimated by digital examination and was subdivided into three groups:
      smaller than or equal to walnut size, small hen's egg size and equal to or larger
      than hen's egg size. Firstly, relationships of sex hormone levels with age were
      studied. There was a slight decrease in Total-T over 60 years old, a significant
      decrease in Free-T, and no change in E2 with age. Thus, E2/Total-T and E2/Free-T
      ratio increased significantly after middle-age. Secondly, relationships of
      hormone levels with prostatic size were studied. In the larger prostate group, a
      significantly lower level of Total-T and significantly higher level of E2 were
      detected. But there was no difference in Free-T. Thus, the prostatic size was
      correlated positively with E2 level, E2/Total-T and E2/Free-T ratio. These
      suggest that the endocrine environment tended to be estrogens-dominant with age,
      in particular, after middle-age, and that patients with large prostates have more
      estrogens-dominant environments. We conclude that estrogens are key hormones for
      the induction and the development of BPH.

PMID- 1379659
TI  - [The status of biological risk factors and the optimality concept in diagnosis of
      early childhood developmental disorders].
AB  - In a prospective study the psychomotor development up to the end of the second
      year of life of 409 preterm and term newborn infants was examined in order to
      identify which optimality score might be associated with disturbances of normal
      childlike development. Significant connections between 24 and 55 risk factors and
      the mortality could be demonstrated, but only 3 factors (sex, apgar, acidosis)
      exert influence on psychomotor development. The risk loading of the collective
      was high, not one of the children showed an optimal score. Decreased patients
      possessed a stronger reduced optimality than survivors. The optimality concept is
      not suitable for the prediction of later disturbed development of children,
      because the items are unspecific. The marker of hypoxia, the erythrocytic-density
      test, as well as the neuron-specific enolase showed better diagnostic values than
      the optimality concept.

PMID- 1379660
TI  - The safety and efficacy of ten percent pentastarch as a cardiopulmonary bypass
      priming solution. A randomized clinical trial.
AB  - Ten percent pentastarch is a low-molecular-weight hydroxyethyl starch with
      greater oncotic pressure and shorter intravascular persistence than 6%
      hetastarch. To evaluate its safety and efficacy as a component of cardiopulmonary
      bypass priming solution, we prospectively studied 90 patients undergoing coronary
      artery bypass grafting or valve replacement necessitating cardiopulmonary bypass
      (bubble oxygenator and moderate systemic hypothermia). Sixty patients were
      randomized to receive 75 gm of either 10% pentastarch (group P) or 25% albumin
      (group A), and 30 patients received lactated Ringer's solution alone (group C).
      Intravascular colloid osmotic pressure during cardiopulmonary bypass was highest
      with either of the colloid primes (15-minute measurement: group P, 15.7 +/- 2.2
      mm Hg (mean +/- standard deviation); group A, 15.2 +/- 2.0 mm Hg; group C, 11.3
      +/- 1.7 mm Hg; p less than 0.05, groups P and A compared with group C). This was
      associated with a lower volume requirement during cardiopulmonary bypass to
      maintain the venous reservoir (group P, 333 +/- 318 ml; group A, 483 +/- 472 ml;
      group C, 1332 +/- 1013 ml; p less than 0.05, groups P and A compared with group
      C). Urine output during cardiopulmonary bypass was similar in each group. Net
      intraoperative fluid balance was lowest in the colloid groups (groups P and A,
      5.7 +/- 1.4 L; group C, 6.9 +/- 1.3 L; p less than 0.05, groups P and A compared
      with group C). Cardiac index shortly after weaning from cardiopulmonary bypass
      was greatest in group P (group P, 3.2 +/- 0.9; group A, 2.8 +/- 0.8; group C, 2.7
      +/- 0.6 dyne.sec.cm-5; p less than 0.05, group P compared with group C). Changes
      in alveolar-arterial oxygen gradients, shunt fraction, and effective compliance
      were similar in all groups. During cardiopulmonary bypass, pentastarch appeared
      to cause the greatest degree of hemodilution, as suggested by the lowest
      hemoglobin, factor VII and IX levels and platelet count. The activated partial
      thromboplastin time was significantly prolonged during and immediately after
      cardiopulmonary bypass in group P relative to groups A and C (p less than 0.05),
      although there were no significant differences in the activated clotting time
      before cardiopulmonary bypass, during cardiopulmonary bypass, or after heparin
      neutralization. As well, clinical indices of hemostasis, including mediastinal
      drainage, red cell, platelet, and fresh frozen plasma requirements, and
      reoperation for excessive postoperative bleeding, were similar. We conclude that
      pentastarch, when used in cardiopulmonary bypass prime, is as safe as either
      albumin or Ringer's solution alone.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1379661
TI  - Late sudden cardiac death in the follow-up of patients having a heart valve
      prosthesis.
AB  - Eight hundred thirty-one patients with Bjork-Shiley prostheses (341 aortic, 345
      mitral, and 145 double) had a mean follow-up time of 68.2 months per patient. Of
      these, 24 (16% of all deaths) died suddenly: six of 42 with aortic valve
      replacement (14.3%), 12 of 56 with mitral valve replacement (21.4%), and six of
      36 with double valve replacement (16.6%). This correlated with evidence of
      premature ventricular complexes detected in multiple routine 12-lead follow-up
      electrocardiograms (p less than 0.001 for simple aortic or mitral valve
      replacements and p less than 0.01 for combined aortic and mitral valve
      replacements). Premature ventricular complexes were significantly more frequent
      among those who died suddenly than among survivors and those who died of other
      causes (p less than 0.001 in both cases); there were no significant differences
      between the latter two groups. The actuarial risk of sudden death was
      significantly greater among those patients who had premature ventricular
      complexes than among those who did not have this disorder (p = 0.0002). We
      conclude that the presence of premature ventricular complexes, as an independent
      variable, was correlated with the risk of sudden death.

PMID- 1379662
TI  - Soft tissue sarcoma, aplastic anaemia, and exposure to pesticides.

PMID- 1379663
TI  - Prognostic value of serum beta 2-microglobulin in HIV infection.

PMID- 1379664
TI  - Treatment of recurrent head and neck cancer with cisplatin and 5-fluorouracil vs.
      the same plus bleomycin and methotrexate.
AB  - A prospective randomized trial of 62 patients with recurrent squamous cell
      carcinoma of the head and neck was conducted to compare the effectiveness of our
      standard chemotherapy program with that of our test regimen. The standard
      chemotherapy regimen consisted of cisplatin 80 mg/M2 on day 1 followed by 5
      fluorouracil 800 mg/M2 days 2 through 6. Our test regimen consisted of the same
      two drugs plus 15 U bleomycin on day 1 and methotrexate 100 mg/M2 on day 16
      followed in 24 hours with 15 mg leucovorin every 6 hours for six doses. One
      patient in each arm of the study was not evaluated. Among 29 patients receiving
      the two-drug regimen, there was 1 complete response and 10 partial responses (38%
      response rate). Among 31 patients receiving the four-drug regimen, there were 3
      complete responses and 16 partial responses (61% response rate; two vs. four-drug
      regimen, P = .06). The failure-free survival in the four-drug group was better
      than the two-drug group, median 4.5 vs. 2.3 months (P = .02). The overall
      survival for both groups was the same (median of 7.8 months). A detailed analysis
      of toxicity did not reveal any important differences between the two regimens.
      The addition of bleomycin and methotrexate to our cisplatin and 5-fluorouracil
      regimen resulted in an increase in effectiveness without adding toxicity.

PMID- 1379665
TI  - Demonstration of synergistic effects of hyperthermia and photodynamic therapy
      using the chick chorioallantoic membrane model.
AB  - The chick chorioallantoic membrane (CAM) model was used to study vascular effects
      of photodynamic therapy (PDT) and hyperthermia (HPT) and the synergism of these
      modalities. The CAM is a convenient medium for monitoring the modifications of
      the vasculature. It is possible to view the CAM and to examine structural changes
      of individual blood vessels in real time. Moreover, the CAM is a closed system
      which lends itself to mathematical modeling of the temporal and spatial
      temperature profile and in which HPT can be performed quantitatively and to a
      selected depth, using different lasers. A porphyrin-type photosensitizer solution
      was applied to areas of the CAM, defined by teflon O-rings placed on the surface.
      Uptake dynamics of the sensitizer into the CAM was determined by analyzing its
      fluorescence in vivo. The CAM area was irradiated with a dual-wavelength laser
      system composed of a dye laser at 644 nm (to induce PDT) and a CO2 laser at 10.6
      microns (to bring about HPT). Damage to the CAM vasculature, due to combined
      PDT+HPT, was compared to the outcome of the separate modalities, and a
      synergistic effect of about 40% was observed.

PMID- 1379667
TI  - Synthesis and transport of GAP-43 in entorhinal cortex neurons and perforant
      pathway during lesion-induced sprouting and reactive synaptogenesis.
AB  - Metabolic labeling and quantitative 2D gel autoradiography were used to assess
      changes in the synthesis and transport of GAP-43 in entorhinal cortex (EC)
      neurons and perforant pathway during lesion-induced sprouting and reactive
      synaptogenesis. In normal adult rats, there is a high constitutive level of GAP
      43 synthesis and transport in EC neurons projecting to the hippocampus. Following
      unilateral EC lesions, there is a 2-fold (100%) increase in the transport of
      newly synthesized GAP-43 to the contralateral or 'sprouting' hippocampus. The
      timing of this upregulation (between 6 and 15 days) suggests that changes in GAP
      43 expression occur in response to the growth of presynaptic terminals during
      sprouting.

PMID- 1379666
TI  - Cloning and functional expression of a cDNA encoding the mouse beta 2 subunit of
      the kainate-selective glutamate receptor channel.
AB  - The primary structure of the mouse glutamate receptor beta 2 subunit has been
      deduced by cloning and sequencing cDNA. The beta 2 subunit has structural
      characteristics common to the subunits of glutamate-gated ion channels.
      Expression of the cloned cDNA in Xenopus oocytes yields functional glutamate
      receptor channels selective for kainate.

PMID- 1379668
TI  - PCR-amplified length polymorphisms in tRNA intergenic spacers for categorizing
      staphylococci.
AB  - The intergenic spacers between some adjacent tRNA genes were shown to be
      polymorphic in length when closely related Staphylococcus species were compared.
      A simple procedure was developed to detect and sequence these tRNA intergenic
      length polymorphisms (tRNA-ILPs). A comparison of homologous tRNA gene sequences
      flanking these ILPs in three Staphylococcus species was used to derive primers
      for high-stringency amplification of the ILPs by the polymerase chain reaction
      (PCR). The detection of tRNA-ILPs by PCR allowed the classification of virtually
      all strains from the five species of Staphylococcus that were examined. The
      procedure used to identify, sequence and derive primers for PCR detection of tRNA
      ILPs in Staphylococcus should be applicable to many other genera of eubacteria.
      These primers could be used on uncultured material such as clinical samples.

PMID- 1379669
TI  - In vitro and in vivo analysis of transcription within the replication region of
      plasmid pIP501.
AB  - Derivatives of the conjugative streptococcal plasmid pIP501 replicate stably in
      Bacillus subtilis. The region essential for replication of pIP501 has been
      narrowed down to a 2.2 kb DNA segment, the sequence of which has been determined.
      This region comprises two genes, copR and repR, proposed to be involved in copy
      control and replication. By in vitro and in vivo transcriptional analysis we
      characterized three active promoters, pI, pII and pIII within this region. A
      putative fourth promoter (pIV) was neither active in vitro nor in vivo. We showed
      that copR is transcribed from promoter pI while the repR gene is transcribed from
      promoter pII located just downstream of copR. The pII transcript encompasses a
      329 nucleotide (nt) long leader sequence. A counter transcript that was
      complementary to a major part of this leader was found to originate from a third
      promoter pIII. The secondary structure of the counter transcript revealed several
      stem-loop regions. A regulatory function for this antisense RNA in the control of
      repR expression is proposed. Comparative analysis of the replication regions of
      pAM beta 1 and pSM19035 suggested a similar organization of transcriptional
      units, suggesting that an antisense RNA is produced by these plasmids also.

PMID- 1379670
TI  - Localised mutagenesis of the fts YEX operon: conditionally lethal missense
      substitutions in the FtsE cell division protein of Escherichia coli are similar
      to those found in the cystic fibrosis transmembrane conductance regulator protein
      (CFTR) of human patients.
AB  - After localised mutagenesis of the 76 min region of the Escherichia coli
      chromosome, we isolated a number of conditionally lethal mutants. Some of these
      mutants had a filamentation temperature sensitive (fts) phenotype and were
      assigned to the cell division genes ftsE of ftsX, whereas others were defective
      in the heat shock regulator gene rpoH. Both missense and amber mutant alleles of
      these genes were produced. The missense mutant ftsE alleles were cloned and
      sequenced to determine whether or not the respective mutations mapped to the
      region of the gene encoding the putative nucleotide binding site. Surprisingly,
      most of these mutant FtsE proteins had missense substitutions in a different
      domain of the protein. This region of the FtsE protein is highly conserved in a
      large family of proteins involved in diverse transport processes in all living
      cells, from bacteria to man. One of the proteins in this large family of
      homologues is the human cystic fibrosis transmembrane conductance regulator
      (CFTR), and the FtsE substitutions were found to be in very closely linked, or
      identical, amino acid residues to those which are frequently altered in the CFTR
      of human patients. These results confirm the structural importance of this highly
      conserved region of FtsE and CFTR and add weight to the current structural model
      for the human protein.

PMID- 1379671
TI  - Structure and functional expression of the acid-labile subunit of the insulin
      like growth factor-binding protein complex.
AB  - Nearly all of the insulin-like growth factor (IGF) in the circulation is bound in
      a heterotrimeric complex composed of IGF, IGF-binding protein-3, and the acid
      labile subunit (ALS). Full-length clones encoding ALS have been isolated from
      human liver cDNA libraries by using probes based on amino acid sequence data from
      the purified protein. These clones encode a mature protein of 578 amino acids
      preceded by a 27-amino acid hydrophobic sequence indicative of a secretion
      signal. Expression of the cDNA clones in mammalian tissue culture cells results
      in the secretion into the culture medium of ALS activity that can form the
      expected complex with IGF-I and IGF-binding protein-3. The amino acid sequence of
      ALS is largely composed of 18-20 leucine-rich repeats of 24 amino acids. These
      repeats are found in a number of diverse proteins that, like ALS, participate in
      protein-protein interactions.

PMID- 1379672
TI  - Analysis of DNA sequences required for pituitary-specific expression of the
      glycoprotein hormone alpha-subunit gene.
AB  - Transient transfection studies have been used to determine the DNA sequences of
      the glycoprotein hormone alpha-subunit gene that are required for tissue-specific
      expression. In the initial phase of these studies, a variant mouse alpha gene was
      identified which contains a fully palindromic cAMP response element (CRE). The
      corresponding region of a previously cloned and sequenced mouse alpha gene
      contains a single point mutation that disrupts the symmetrical nature of this
      element. DNase footprint studies demonstrate that the fully palindromic CRE binds
      the CRE-binding protein with much higher affinity than the imperfect palindrome.
      Transfection experiments using both mouse alpha gene variants demonstrate
      differences in basal and cAMP-induced expression. Studies of the cAMP response of
      the human alpha gene indicated that this gene contains sequences other than the
      known CRE that are sufficient to permit a transcriptional response to cAMP in
      both placental and pituitary cells. Expression of human and mouse alpha-subunit
      genes has been examined in cells of the gonadotrope, thyrotrope, and trophoblast
      lineages to identify DNA sequences that mediate selective transcription of the
      alpha gene in these cells. The results demonstrate that sequences between about 
      500 and -200 are important for expression in the pituitary, but not the placenta.
      Clustered point mutations were used to further characterize sequences required
      for expression in the pituitary. Two regions, one at positions -445 to -438 and
      one at positions -337 to -330, were required for expression in cells of the
      gonadotrope lineage. One of these regions, at -337 to -330, is also important for
      expression in thyrotropes. When linked to a minimal promoter, multiple copies of
      the -344 to -300 region had transcriptional enhancer activity in gonadotropes and
      thyrotropes, but not in several other cell types. These results are consistent
      with a model involving different combinations of regulatory elements that
      determine cell-specific alpha expression in gonadotropes and thyrotropes.

PMID- 1379673
TI  - The carboxy-terminal region of the glycoprotein hormone alpha-subunit:
      contributions to receptor binding and signaling in human chorionic gonadotropin.
AB  - The glycoprotein hormones are heterodimeric and contain a common alpha-subunit,
      which is noncovalently associated with a hormone-specific beta-subunit. The alpha
      subunit has been highly conserved throughout evolution; for example, the five
      amino acid residues of the carboxy-terminus, Tyr-Tyr-His-Lys-Ser-COOH, are
      identical in nine of the 10 available amino acid sequences. It has been shown
      that enzymatic removal of these five amino acid residues, while not affecting
      holoprotein formation, results in a heterodimer that exhibits very little, if
      any, binding to the CG/LH receptor. Using site-directed mutagenesis on the human
      alpha-subunit, we have prepared two deletion mutants, Des-(88-92)alpha and Des
      (89-92)alpha, and two point mutants, where each of the two tyrosines, 88 and 89,
      was replaced with phenylalanine, in order to delineate more specifically the
      contributions of these aromatic side-chains to receptor binding. The cDNAs for
      wild-type hCG alpha and mutants were introduced into a pcDNAINEO expression
      vector, and the cDNA for hCG beta was inserted into a pRSV plasmid; both were
      transiently cotransfected into DUXB-11 cells. The media were collected, and RIAs
      showed that all mutants formed heterodimers; moreover, there was no discernable
      difference in subunit assembly between wild-type hCG alpha and the various mutant
      alpha-subunits. The gonadotropin mutants were assayed in vitro using a
      competitive binding assay with [125I]hCG and stimulation of progesterone
      production in the transformed murine Leydig cell line MA-10.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1379674
TI  - A single gene encodes the beta-subunits of equine luteinizing hormone and
      chorionic gonadotropin.
AB  - Equine (e) CG and LH beta-subunits have identical amino acid sequences, including
      an extended carboxyl-terminal peptide (CTP). This suggests that unlike the
      corresponding human genes, the beta-subunits of eCG and eLH may be encoded by a
      single gene and share a common proximal promotor region. To explore this, we
      isolated and characterized the eLH/CG beta gene(s). Data from Southern analyses
      suggest that the eCG beta and eLH beta subunits are products of the same single
      copy gene (eLH/CG beta). Overlapping fragments of the eLH/CG beta gene and cDNA
      were amplified from equine genomic DNA and pituitary gland mRNA by the polymerase
      chain reaction, cloned, and sequenced. The eLH/CG beta gene spans less than 1.2
      kilobase-pairs and has three exons that translate a CTP-containing polypeptide
      identical in sequence to that previously reported for the mature equine protein.
      There is, however, little amino acid homology shown between the CTP of human or
      equine CG beta subunit. In addition, unlike the human genes, the same TATAA-like
      element appears to be involved in directing initiation of transcription of the
      eLH/CG beta gene in placenta and anterior pituitary. Based upon these
      differences, we suggest that the CG beta genes evolved independently in humans
      and equids and that different mechanisms are involved in their patterns of
      placenta-specific expression.

PMID- 1379676
TI  - Structural origin of the immunological diversity of two closely related
      tetrapeptides: CIDNP study of TyrTyrGluGlu and TyrGluTyrGlu epitopes.
AB  - Photochemically induced dynamic nuclear polarization (photoCIDNP) measurements,
      specific for exposed tyrosine residues, have been applied to elucidate
      conformational differences responsible for the immunological diversity of the
      synthetic multichain copolymers, Tyr1Tyr2Glu3Glu4-poly-DL-Ala-poly-Lys and
      Tyr1Glu2Tyr3Glu4-poly-DL-Ala-poly-LS. These two copolymers are essentially
      identical in their molecular weight, size, shape and composition, and differ only
      in the order of the two internal amino acid residues within the sequence of the
      tetrapeptide epitopes. Nonetheless, previous studies have shown that the two
      macromolecules behave differently, as evidenced by their immunological and
      immunogenic properties. As immunogens they act under different genetic control
      mechanisms, and differ in their interactions with antigen presenting cells, T
      cells and B cells. Antibodies elicited against these two antigens do not cross
      react. The photoCIDNP measurements of these two polymers, intended to elucidate
      discrete structural differences controlling immune recognition, showed that in
      the TyrTyrGluGlu polymer, Tyr1 and Tyr2 rings are free, non-interacting and
      undergo fast internal rotation. Computed minimum energy conformations confirm
      these conclusions and indicate that Tyr1 and Tyr2 point to different regions in
      space. In TyrGluTyrGlu, however, CIDNP measurements give rise to one broad
      tyrosine 3,5 proton signal, the result of a strong Tyr1-Tyr3 hydrophobic
      interaction. These two tyrosine residues are thus close in space, and undergo
      slow internal rotation. These results are in agreement with the computed minimum
      energy conformations.

PMID- 1379675
TI  - Expression of hepatic insulin-like growth factor-I and insulin-like growth factor
      binding protein-1 genes is transcriptionally regulated in streptozotocin-diabetic
      rats.
AB  - Insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (BP-1) are
      critical cell regulators, with regulation and action in endocrine, paracrine, and
      autocrine modes. Although IGF-I and BP-1 are thought to be modulated mainly at
      the level of synthesis, underlying molecular mechanisms are poorly understood. To
      examine regulation by insulin, we used run-on assays to measure IGF-I and BP-1
      gene transcription rates in nuclei isolated from the livers of normal and
      diabetic rats. Streptozotocin (STZ)-treated rats exhibited 20-25% weight loss, a
      2.5- to 3-fold increase in serum glucose, and a 50-60% fall in circulating IGF-I
      levels (all P less than 0.001). Diabetic animals also had a 45% reduction in
      hepatic IGF-I mRNA and over 400% increases in BP-1 mRNA (both P less than 0.005);
      all parameters were restored toward normal after treatment with insulin.
      Metabolically responsive IGF-I gene transcription was evaluated effectively with
      a 3.2-kilobase BglII/EcoRI genomic probe located down-stream from all initiation
      sites in exon 1, while BP-1 gene transcription was studied with a cDNA probe.
      Animals treated with 144 mg/kg STZ exhibited 50-97% decreases in IGF-I gene
      transcription (P less than 0.05), while insulin treatment raised IGF-I gene
      transcription to control levels (P less than 0.02). IGF-I gene transcription
      appeared to be more sensitive to metabolic status than IGF-I mRNA levels,
      resulting in a modest correlation between transcription rates and mRNA levels (r
      = 0.68; P less than 0.001). In contrast, changes in BP-1 mRNA and gene
      transcription appeared to be exquisitely sensitive to metabolic status.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1379677
TI  - Recognition of multiple epitopes in the coiled-coil domain of lamin B by human
      autoantibodies.
AB  - The nuclear lamina of mammalian cells consists of three major proteins, lamins A,
      B and C, which form a fibrous meshwork interposed between the inner nuclear
      membrane and the chromatin. Sera from certain patients with systemic lupus
      erythematosus (SLE) and autoimmune liver disease contain high titers of
      autoantibodies against lamin B. We have shown previously that anti-lamin B
      autoantibodies in SLE recognize epitopes highly specific for lamin B, even though
      lamin B and lamins A/C are highly homologous proteins. To further characterize
      the specificities of these autoantibodies, fusion proteins carrying fragments of
      lamins B and C were tested for reactivity with SLE sera by immunoblotting. Five
      distinct epitopes of lamin B were identified, at least four of which were located
      in the highly conserved coiled-coil rod domain. Epitopes located on amino acids
      (AA) 80-193 and 245-303 were recognized by 4/10 and 8/10 anti-lamin B positive
      sera, respectively. Affinity purified anti-lamin B autoantibodies reacted
      preferentially with lamin B, indicating that they recognized mainly portions of
      lamin B that differ from lamins A and C. On the contrary, most of the affinity
      purified anti-lamin C autoantibodies from SLE sera cross-reacted with lamin B,
      suggesting that the anti-nuclear lamina immune response in these patients is
      directed primarily against lamin B. The preferential reactivity of these sera
      with multiple epitopes specific to lamin B, and the finding that the
      autoantibodies to lamins A and C present in some of these sera cross-react with
      lamin B suggest that autoantibodies to lamin B are generated in response to the
      authentic lamin B protein rather than a cross-reactive foreign protein.

PMID- 1379678
TI  - At least five antigenic epitopes on the streptokinase molecule are recognized by
      human CD4+ TCR alpha beta+ T cells.
AB  - The streptokinase molecule (415 AA) was cleaved at methionine 237, 347 and 370
      yielding four polypeptide fragments. Human HLA-class II restricted streptokinase
      specific T cell clones and cell lines (CD2+, CD3+, CD4+, CD8-, TCR alpha beta+,
      TCR gamma delta-) recognized antigenic epitopes on all four fragments AA 1-236,
      AA 238-346, AA 348-369 and AA 371-415. T cell clones recognizing fragment AA 1
      236 were restricted by at least two different HLA-class II elements, this
      indicating that more than one antigenic epitope can be recognized on this
      fragment. In addition, two streptokinase-specific T cell clones recognized only
      the intact molecule and none of the molecular fragments. These two clones
      probably recognized an antigenic epitope including one of the methionine residues
      used for molecular cleavage. We conclude that T cell proliferative responses to
      streptokinase are determined by recognition of at least five different antigenic
      epitopes distributed along the entire streptokinase polypeptide chain.

PMID- 1379679
TI  - Demethylation of the constant region genes of immunoglobulins reflects the
      differentiation state of the B cell.
AB  - Previous results showed a developmentally regulated, strong linkage between
      demethylation and transcriptional activity for the light chain kappa locus in the
      mouse (Kelley et al., Molec. cell. Biol. 8, 930-937, 1988). These results
      indicate the existence of a stage of development of the B cell in which permanent
      expression (which may be enhancer independent) of a gene is associated with its
      demethylation. According to this result, demethylation could mirror terminal
      differentiation of a cell. We tested this hypothesis by analyzing the methylation
      status of immunoglobulin (Ig) genes in normal B cells before and after their
      activation with lipopolysaccharide (LPS) to induce IgM secretion and an
      immunoglobulin class switch. This pattern of methylation has been compared with
      that of Ig genes in nonlymphoid tissues and in transformed cell lines. In
      general, transformed cells are terminally differentiated cells. Our results show,
      that in normal splenic B cells only regions proximal to the heavy chain enhancer
      are demethylated. The coding regions of the c mu, c delta and the c gamma 1 genes
      remain methylated regardless of transcription. Demethylation of the coding
      regions is only detectable in transformed cell lines. Hence demethylation of
      immunoglobulin genes may reflect a stage of terminal differentiation in which the
      transcription pattern of the cell is fixed. Methylation of the genes before
      terminal differentiation may be necessary to allow controlled expression of genes
      on the transcriptional level, such as by splicing and differential termination.

PMID- 1379680
TI  - Variable region cDNA sequences of three mouse monoclonal anti-idiotypic
      antibodies specific for anti-alpha(1----6)dextrans with groove- or cavity-type
      combining sites.
AB  - The variables regions of three syngeneic anti-idiotypic antibodies (Ab2s) were
      cloned and sequenced. They are encoded by different VL genes, two are from
      different members of V kappa-Ox1 superfamily. The H chains are encoded by VH
      genes belonging to three different VH families, J558, Q52 and 7183. Together with
      a previous report from this laboratory, the nucleotide sequences of four Ab2s to
      anti-alpha(1----6)dextrans have been presented. They are derived from a number of
      unrelated germline genes, and differ from similar studies in anti-NP, anti-GAT
      and anti-Ars systems. Three of four Ab2s in the anti-alpha(1----6)dextran system
      appear to have D-D fusions, which has also been reported in several other Ab2s.

PMID- 1379681
TI  - The peptide binding specificity of HLA class I molecules is largely allele
      specific and non-overlapping.
AB  - To understand better the specificity of peptide binding by MHC class I molecules,
      we have evaluated the capacity of a panel of unrelated peptides to compete for
      the presentation of viral peptides presented by HLA-A3 and HLA-B27. The HIV-Nef7F
      peptide (74-82) was presented by HLA-A3 to Nef-specific HLA-A3-restricted CTL
      lines, and the influenza nucleoprotein peptide NP(380-393) was presented by HLA
      B27 to NP(380-393)-specific HLA-B27-restricted CTL lines. In addition, we have
      extended studies from our group that have evaluated the capacity of a similar
      panel of peptides to inhibit presentation of an influenza nucleoprotein peptide
      NP (335-349) by HLA-B37 and a matrix peptide, M1 (57-68), by HLA-A2 to the
      appropriate peptide-specific CTL lines. Out of 41 peptides tested, only five
      bound to more than one of the MHC molecules analyzed. Pairwise comparisons of the
      peptide binding specificities among these four different class I molecules
      revealed no common competitor peptides in four of the six possible comparisons.
      Thus, each class I molecule appears to have a functionally distinct peptide
      binding site, as reflected by the ability to bind largely non-overlapping sets of
      peptides.

PMID- 1379682
TI  - Localisation of linear epitopes at the carboxy-terminal end of the mycobacterial
      71 kDa heat shock protein.
AB  - Four distinct linear epitopes localized within species-specific sequences at the
      carboxy-terminal end of the 71 kDa heat shock protein of M. tuberculosis have
      been identified by scanning 94 overlapping peptides with 13 human sera. One
      epitope ("C") of entirely M. tuberculosis-specific core sequence (GEAGPG) has
      been found immunogenic in smear-negative tuberculosis, but not in non-tuberculous
      mycobacterial diseases. This peptide appears to be a valuable candidate for
      further serodiagnostic evaluation.

PMID- 1379683
TI  - Clastogenicity of 2-chlorobenzylidene malonitrile (CS) in V79 Chinese hamster
      cells.
AB  - The clastogenicity of the sensory irritant 2-chlorobenzylidene malonitrile (CS)
      to V79 Chinese hamster cells was investigated at various exposure conditions. CS
      efficiently induced chromatid-type aberrations in a dose-dependent manner
      provided the cells could run through at least one or two S-phases during a 20-h
      exposure over a 3-h exposure followed by a 20-h recovery period (cell cycle time
      8-10 h). The induction of SCEs indicates an S-dependent mechanism. The hydrolysis
      products o-chlorobenzaldehyde and malonitrile were inactive in these experiments.

PMID- 1379684
TI  - Mutagenicity of methyl methanesulfonate and cyclophosphamide in resting and
      growing Saccharomyces cerevisiae D7 cells.
AB  - In order to evaluate the optimal experimental conditions and to identify the best
      growth phase for yeast genotoxicity studies, comparative experiments were
      performed with stationary and growing cells. Methyl methanesulfonate (MMS) and
      cyclophosphamide (CP) were used as chemical mutagens and strain D7 of
      Saccharomyces cerevisiae as detector of induced mitotic gene conversion (trp+
      convertants) and point reverse mutation (ilv+ revertants) in log or stationary
      phase cells after either 4 or 16 h of treatment. The highest MMS-induced toxicity
      and genotoxicity were observed after 16 h of exposure in a suspension test with
      log phase cells, which is consistent with the greater permeability and
      sensitivity of growing yeast cells. The maximal induction of genetic effects and
      toxicity by CP was conversely obtained after 16 h of treatment in stationary
      phase cells. This may be ascribed to the greater ability of detoxication of
      growing cells as compared to resting cells. Our results suggest that in
      evaluating the mutagenicity of chemicals in yeast systems it is important to
      consider factors such as growth phase and exposure time.

PMID- 1379685
TI  - Decreased electrophilicity of chemicals carcinogenic only at the maximum
      tolerated dose.
AB  - While there was no significant difference between the actual or predicted
      mutagenicity and clastogenicity of a group of chemicals carcinogenic only at the
      maximum tolerated dose (MTD) and a group of chemicals carcinogenic below the MTD,
      as a group, the chemicals carcinogenic below the MTD exhibited a significantly
      decreased LUMO (Lowest Unoccupied Molecular Orbital) energy, indicative of
      increased electrophilicity (i.e. DNA reactivity). These findings suggest that
      chemicals carcinogenic only at the MTD either require increased doses of "weak"
      electrophiles to be carcinogenic or that they may act by a "non-genotoxic"
      mechanism.

PMID- 1379686
TI  - UV resistance of E. coli K-12 deficient in cAMP/CRP regulation.
AB  - Deletion of genes for adenylate cyclase (delta cya) or cAMP receptor protein
      (delta crp) in E. coli K-12 confers a phenotype that includes resistance to UV
      radiation (254 nm). Such mutations lead to UV resistance of uvr+, uvrA, lexA and
      recA strains which could partly be abolished by the addition of cAMP to delta cya
      but not to delta crp strain culture medium. This effect was not related to either
      inducibility of major DNA repair genes or growth rate of the bacteria. Enhanced
      survival was also observed for UV-irradiated lambda bacteriophage indicating that
      a repair mechanism of UV lesions was involved in this phenomenon.

PMID- 1379687
TI  - Inhibition of sulfotransferase affecting unscheduled DNA synthesis induced by 2
      acetylaminofluorene: an in vivo and in vitro comparison.
AB  - The unscheduled DNA repair (UDS) assay was conducted using the in vivo and in
      vitro procedures to investigate the role of arylsulfotransferases (AST) in the
      genotoxicity of 2-acetylaminofluorene (AAF). The in vivo assay had 4 groups of
      rats that consisted of those treated with pentachlorophenol (PCP), PCP and AAF,
      or AAF and an untreated control. The in vitro assay used hepatocytes from 3
      methylcholanthrene or corn oil (control) treated rats. In both the in vivo and in
      vitro UDS assays AAF induced DNA damage. PCP, an inhibitor of
      arylsulfotransferase, significantly decreased AAF induced DNA damage. In the in
      vivo assay, PCP induced a significant increase in UDS and confounded an
      investigation of the role of sulfotransferase. The in vitro UDS assay more
      clearly defined the effect of PCP on AAF genotoxicity.

PMID- 1379688
TI  - Chromosomal analysis of Chinese hamster V79 cells exposed to multiple gamma-ray
      fractions: induction of adaptive response to mitomycin C.
AB  - Chinese hamster V79 cells were irradiated daily with 0.3 Gy of gamma-rays 5 times
      per week for 12 weeks (total 18 Gy). These cells were challenged with an
      additional dose of 15. Gy gamma-rays or treated with 5 micrograms/ml of mitomycin
      C (MMC) for 2 h. In spite of the high total accumulated dose of gamma-rays, the
      number of chromosomal aberrations and sister-chromatid exchanges (SCEs) did not
      significantly increase in the preirradiated cells, as compared to control cells.
      If preirradiated cells were challenged with an additional 1.5 Gy of gamma-rays,
      an insignificant decrease in the yield of chromatid aberrations was observed. In
      contrast, preirradiated cells became significantly more resistant to the
      induction of chromosomal damage when challenged with mitomycin C. Our results
      suggest that multiple fractions of gamma-rays can induce the adaptive response to
      mitomycin C in preirradiated cells.

PMID- 1379689
TI  - X-rays, microwaves and vinyl chloride monomer: their clastogenic and aneugenic
      activity, using the micronucleus assay on human lymphocytes.
AB  - Chromosome aberration assays, sister-chromatid exchange techniques and
      micronucleus assays are commonly used methods for biomonitoring genetic material
      damaged by chemical or physical agents. On the other hand, their aneugenic
      activity, which can lead to hypoploidy and may also be associated with
      carcinogenesis, has not been thoroughly investigated. In our study we chose the
      micronucleus assay with a new mathematical approach to separate clastogenic from
      aneugenic activity of three well-known mutagens (vinyl chloride monomer, X-rays
      and microwaves) on the genome of human somatic cells. The comparison of
      frequencies of size distribution of micronuclei in the lymphocytes of humans
      exposed to each of these three mutagens showed that X-rays and microwaves were
      preferentially clastogens while vinyl chloride monomer showed aneugenic activity
      as well. Microwaves possess some mutagenic characteristics typical of chemical
      mutagens.

PMID- 1379690
TI  - Purified prostaglandin synthase activates aromatic amines to derivatives that are
      mutagenic to Salmonella typhimurium.
AB  - Prostaglandin H synthase (PHS) is widely distributed in mammalian tissues and has
      the ability to oxidize a variety of mutagens and carcinogens. It may therefore
      play a key role in the metabolic activation of xenobiotics. The present study
      documents that highly purified PHS can be used in conjunction with 5-phenyl-4
      pentenyl-1-hydroperoxide (PPHP), a relatively stable and non-mutagenic
      hydroperoxide substrate, for the metabolic activation of aromatic amines to
      mutagenic derivatives that can be detected in short-term Salmonella typhimurium
      mutagenesis assays. The PHS-based activation system alone was not mutagenic for
      these tester strains, nor were the test compounds significantly toxic for the
      bacteria over the concentration range tested. When used in conjunction with
      Salmonella strains TA98 and TA100 in a modified Ames assay, this system should
      prove useful for screening of a wide range of compounds for metabolic activation
      by this mammalian peroxidase. The potential broad utility of this purified PHS
      dependent metabolic activation system was investigated by evaluating the
      activation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4
      dimethylimidazo[4,5-f]quinoline (MeIQ), which are representative of a group of
      mutagenic and carcinogenic heterocyclic arylamines to which humans are exposed
      via their diet. Both IQ and MeIQ were activated by PHS to potent mutagens and
      confirm the utility of the PPHP/PHS system for the activation of premutagens.
      Whereas the extent of activation of aromatic amines by S9-based systems is
      significantly greater than for the PHS activation system described herein, PHS
      may play a significant role in target tissues in which it is present at
      significantly greater levels than P450 isoenzymes. Moreover, it is likely that
      the substrate specificity of PHS differs sufficiently from that of P450
      isoenzymes so that PHS may activate some compounds that are not efficiently
      activated by mixed-function oxidase based systems.

PMID- 1379691
TI  - Are mitotic index and lymphocyte proliferation kinetics reproducible endpoints in
      genetic toxicology testing?
AB  - Lymphocyte proliferation kinetics is an endpoint used in genetic toxicology which
      has recently been proposed as an alternative for the screening of new cytostatic
      drugs. Although great variability for this parameter has been reported, there are
      few reports about the intra- and inter-individual variation of the effects of
      chemicals on this endpoint. For this reason, experiments were conducted to
      evaluate the reproducibility of the effects of a well-known cytostatic, mitomycin
      C (MMC), on the proliferation of PHA-stimulated human lymphocytes, both over time
      and among samples from several donors. Although inter-individual variability was
      shown in both parameters in untreated and treated cultures, this variation was
      not significant. Intra-individual variation was significantly detected only in
      cultures treated with 0.1 microM MMC.

PMID- 1379692
TI  - Dextrans as markers for endocytosis in innervated and denervated skeletal muscle.
AB  - Fluorescence-labeled dextrans were evaluated as markers for endocytosis in
      skeletal muscle. Fluorescein isothiocyanate (FITC)-labeled dextrans (average
      molecular weight 3900 to 71200) showed a higher uptake in denervated than in
      innervated muscle both in vitro and in vivo. The in vitro uptake of FITC-dextran
      (35.600) increased linearly with time at 37 degrees C, and was almost completely
      inhibited by low temperature (4 degrees C). The uptake was not a pure bulk
      uptake, because a saturable component was evident from the concentration
      dependence and from competition experiments with unlabeled dextran. The uptake of
      FITC-labeled or rhodamine B isothiocyanate (RITC)-labeled dextrans in denervated
      muscle occurred mainly in small segments of the fibers centered around the
      denervated endplate region. However, not all denervated fibers showed such
      segments. Periodic acid Schiff's base staining for carbohydrates stained dextrans
      in denervated muscle fibers. Some staining, probably of lysosomes, was also
      observed in denervated muscle not exposed to dextran.

PMID- 1379693
TI  - Vasculitic neuropathy in a patient with cryoglobulinemia and anti-MAG IGM
      monoclonal gammopathy.
AB  - A patient with sensorimotor mononeuritis multiplex had a type II cryoglobulin
      with an IgM kappa M-protein that appeared to contain monoclonal anti-MAG
      antibodies of the same isotype. A sural nerve biopsy demonstrated necrotizing
      arteritis and features of both axonal degeneration and demyelination. IgM kappa
      and C3 deposits were present on the myelin sheath of some residual nerve fibers.
      The findings suggest that the anti-MAG antibodies contributed to the myelin
      damage, while cryoprecipitates may have caused the vasculitis and axonal
      degeneration.

PMID- 1379694
TI  - Biosensors. NO release for good measure.

PMID- 1379695
TI  - Signal transduction. Fishing in Src-infested waters.

PMID- 1379696
TI  - Crystal structure of the phosphotyrosine recognition domain SH2 of v-src
      complexed with tyrosine-phosphorylated peptides.
AB  - Three-dimensional structures of complexes of the SH2 domain of the v-src oncogene
      product with two phosphotyrosyl peptides have been determined by X-ray
      crystallography at resolutions of 1.5 and 2.0 A, respectively. A central
      antiparallel beta-sheet in the structure is flanked by two alpha-helices, with
      peptide binding mediated by the sheet, intervening loops and one of the helices.
      The specific recognition of phosphotyrosine involves amino-aromatic interactions
      between lysine and arginine side chains and the ring system in addition to
      hydrogen-bonding interactions with the phosphate.

PMID- 1379697
TI  - Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and
      Ca2+ flux but not mitogenesis.
AB  - Stimulation of certain receptor tyrosine kinases results in the tyrosine
      phosphorylation and activation of phospholipase C gamma (PLC gamma), an enzyme
      that catalyses the hydrolysis of phosphatidylinositol (PtdIns). This hydrolysis
      generates diacylglycerol and free inositol phosphate, which in turn activate
      protein kinase C and increase intracellular Ca2+, respectively. PLC gamma
      physically associates with activated receptor tyrosine kinases, suggesting that
      it is a substrate for direct phosphorylation by these kinases. Here we report
      that a fibroblast growth factor (FGF) receptor with a single point mutation at
      residue 766 replacing tyrosine with phenylalanine fails to associate with PLC
      gamma in response to FGF. This mutant receptor also failed to mediate PtdIns
      hydrolysis and Ca2+ mobilization after FGF stimulation. However, the mutant
      receptor phosphorylated itself and several other cellular proteins, and it
      mediated mitogenesis in response to FGF. These findings show that a point
      mutation in the FGF receptor selectively eliminates activation of PLC gamma and
      that neither Ca2+ mobilization nor PtdIns hydrolysis are required for FGF-induced
      mitogenesis.

PMID- 1379698
TI  - Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without
      affecting mitogenesis.
AB  - Stimulation of growth factor receptors with tyrosine kinase activity is followed
      by rapid receptor dimerization, tyrosine autophosphorylation and phosphorylation
      of signalling molecules such as phospholipase C gamma (PLC gamma) and the ras
      GTPase-activating protein. PLC gamma and GTPase-activating protein bind to
      specific tyrosine-phosphorylated regions in growth factor receptors through their
      src-homologous SH2 domains. Growth factor-induced tyrosine phosphorylation of PLC
      gamma is essential for stimulation of phosphatidylinositol hydrolysis in vitro
      and in vivo. We have shown that a short phosphorylated peptide containing
      tyrosine at position 766 from a conserved region of the fibroblast growth factor
      (FGF) receptor is a binding site for the SH2 domain of PLC gamma (ref. 8). Here
      we show that an FGF receptor point mutant in which Tyr 766 is replaced by a
      phenylalanine residue (Y766F) is unable to associate with and tyrosine
      phosphorylate PLC gamma or to stimulate hydrolysis of phosphatidylinositol.
      Nevertheless, the Y766F FGF receptor mutant can be autophosphorylated, and can
      phosphorylate several cellular proteins and stimulate DNA synthesis. Our data
      show that phosphorylation of the conserved Tyr 766 of the FGF receptor is
      essential for phosphorylation of PLC gamma and for hydrolysis of
      phosphatidylinositol, but that elimination of this hydrolysis does not affect FGF
      induced mitogenesis.

PMID- 1379700
TI  - [Anti-HIV treatment, today and in the near future].

PMID- 1379699
TI  - Regulation of focal adhesion-associated protein tyrosine kinase by both cellular
      adhesion and oncogenic transformation.
AB  - Increasing evidence indicates that the integrin family of cell adhesion receptors
      can transduce biochemical signals from the extracellular matrix to the cell
      interior to modulate cell growth and differentiation. We have shown that
      integrin/ligand interactions can trigger tyrosine phosphorylation of a protein of
      M(r) 120,000 (pp120), so it is possible that signal transduction by integrins
      might involve activation of intracellular protein tyrosine kinases as an early
      event in cell binding to the extracellular matrix. Here we report that pp120 is
      identical to the focal adhesion-associated protein tyrosine kinase pp125FAK (refs
      3, 4). We show that tyrosine phosphorylation of this protein is modulated both by
      cell adhesion and transformation by pp60v-src, and that these changes in
      phosphorylation are correlated with increased pp125FAK tyrosine kinase activity.
      A model is proposed to relate these findings to the molecular basis of anchorage
      independent growth of transformed cells.

PMID- 1379701
TI  - Maternal serum screening for fetal Down syndrome in women less than 35 years of
      age using alpha-fetoprotein, hCG, and unconjugated estriol: a prospective 2-year
      study.
AB  - OBJECTIVE: To evaluate prospectively maternal serum screening with alpha
      fetoprotein (AFP), hCG, and unconjugated estriol (uE3) as a screen for fetal Down
      syndrome. METHODS: Women less than 35 years of age were offered screening between
      15-20 weeks' gestation. Screening results calculated by an algorithm to be equal
      to or greater than 1:274 (the risk of a 35-year-old for fetal Down syndrome at
      the second trimester) were considered positive. If gestational age was confirmed
      by ultrasonography, genetic counseling and amniocentesis were offered. RESULTS:
      In the first 2 years of our program, 9530 women were screened, of which 686
      (7.2%) were found to be screen-positive. Ultrasonographic examination explained
      the abnormal values in 379 (4.0%). The remaining 307 (3.2%) received genetic
      counseling and 214 (2.2%) elected amniocentesis or CVS. Four cases of fetal Down
      syndrome and one de novo chromosomal marker were detected. In three additional
      cases of fetal Down syndrome, triple-analyte screening failed to identify the
      pregnancies to be at increased risk. None of the seven cases of fetal Down
      syndrome would have been detected through screening with maternal serum alpha
      fetoprotein (MSAFP) and age alone. CONCLUSIONS: Measurement of MSAFP, hCG, and
      uE3 in women less than 35 years old is an effective screening test for fetal Down
      syndrome, with a sensitivity of 57% in our study and an amniocentesis rate (false
      positive rate) of 3.2%.

PMID- 1379702
TI  - Risk factors for developmental disorders in infants born to women with Graves
      disease.
AB  - OBJECTIVE: To identify risk factors for disorders of fetal growth and thyroid
      function in the presence of maternal Graves disease. METHODS: Two hundred thirty
      pregnancies in gravidas with Graves disease were analyzed. Maternal thyroid
      status was evaluated by serum free thyroxine (T4) or free T4 index, TSH, and TSH
      receptor antibody; personal history of thyrotoxicosis and total dose of
      antithyroid drugs during pregnancy were also noted. Neonatal thyroid function was
      assessed at birth and on the fifth day after birth. RESULTS: Fifteen neonates
      (6.5%) were small for gestational age (SGA), and this occurrence was
      significantly associated with thyrotoxicosis lasting for 30 weeks or more of
      pregnancy, TSH-receptor antibody level of 30% or more at delivery, history of
      Graves disease of 10 years or longer, and onset of Graves disease before 20 years
      of age. However, no significant correlation was found between maternal thyroid
      hormone level and SGA neonates. Thyroid dysfunction developed in 38 infants
      (16.5%), of whom only four were SGA; development of this dysfunction was
      significantly related to the mother's total dose of antithyroid drugs, duration
      of thyrotoxicosis in pregnancy, and/or TSH-receptor antibody level at delivery.
      CONCLUSIONS: Duration of maternal Graves disease or thyrotoxicosis, either mild
      chemical or overt, in pregnancy is significantly associated with SGA neonates.
      Neonatal thyroid dysfunction is associated with the maternal thyroid condition,
      especially the serum TSH-receptor antibody level.

PMID- 1379703
TI  - Outcome of children born to women treated during pregnancy for the
      antiphospholipid syndrome.
AB  - OBJECTIVE: To determine the rate of neonatal and childhood medical complications
      in the offspring of women with the antiphospholipid syndrome who are treated
      during pregnancy. METHODS: We compared 29 infants born to 23 mothers with
      antiphospholipid syndrome with a group of control children matched for year and
      gestational age at birth and route of delivery. During pregnancy, mothers with
      antiphospholipid syndrome were treated with accepted therapeutic regimens,
      including prednisone and low-dose aspirin, heparin and low-dose aspirin, and
      others. RESULTS: Neonatal complications in the study infants included
      hyperbilirubinemia (14), respiratory distress syndrome (three), bronchopulmonary
      dysplasia (two), necrotizing enterocolitis (two), intraventricular hemorrhage
      (two), neonatal sepsis (one), coarctation of the aorta (one), hypothyroidism
      (one), hypoglycemia (one), and death (one). Two children had feeding problems,
      four had delayed psychomotor development, and eight were small for their age.
      However, the overall rate of neonatal or childhood complications did not differ
      from that in the control children. CONCLUSIONS: Our data indicate that
      prematurity and neonatal problems are common, but the childhood course for these
      offspring is similar to that of other premature infants.

PMID- 1379704
TI  - Microwave-stimulated chemical fixation of whole eyes.
AB  - BACKGROUND: Microwave-stimulated chemical fixation has been used successfully to
      rapidly prepare nonocular tissue for processing and paraffin embedding. METHOD:
      This same technique was adapted to fix whole eyes using a common domestic
      microwave oven. Histologic sections were compared with sections from globes that
      were fixed in a traditional manner. RESULTS: Histologic sections and
      histochemical and immunohistochemical staining of eyes treated with microwave
      stimulated chemical fixation in 10% neutral-buffered formalin were comparable in
      quality to eyes fixed in 10% neutral-buffered formalin at room temperature for 48
      hours. CONCLUSION: Because microwave irradiation accelerates the most time
      consuming part of preparing whole eyes for light microscopy, the technique
      enhances laboratory efficiency. The technique is particularly well suited for
      ensuring adequate fixation of globes when histologic diagnosis is needed in less
      than 48 hours.

PMID- 1379705
TI  - Developing shared decision-making programs to improve the quality of health care.
AB  - We strongly believe in the importance of patient involvement in a medical
      decision. The interactive SDPs appear to be an effective way to facilitate this
      involvement. One key to the acceptance of these programs by patients and
      physicians is that they be--and be perceived as--fair, accurate, and balanced.
      Herein we have described the well-defined protocol for developing, evaluating,
      and updating SDPs. The first of the foundation's programs dealing with benign
      prostatic hyperplasia has been well received by patients and clinicians and has
      been demonstrated to have an impact on practice patterns. Efforts are under way
      to evaluate four additional programs, leading to widespread availability of the
      first five SDPs by fall of 1992.

PMID- 1379706
TI  - Biochemistry of migraine.
AB  - The biochemistry of migraine is complex. Many contradictory or never replicated
      findings in often small patient groups have been published. The following
      observations in the platelet-free plasma and urine appear to have some solid
      basis and will be discussed: 1) systemic derangement of 5-HT metabolism, relevant
      to the peripheral vascular component of migraine pathophysiology, 2) changes in
      neuroexcitatory amino acids and magnesium, which may reflect a predisposition of
      the migraine patient, notably those having attacks with aura, to develop
      spreading depression, 3) alterations in methionine-enkephalin levels, which may
      be a useful marker to discriminate between tension headache and migraine, 4)
      hormonal fluctuations which seem important to set the threshold for an attack, 5)
      changes of vasoactive peptides in the cranio-vascular circulation, providing the
      first human evidence that the trigemino-vascular system indeed is relevant in
      migraine, and 6) catecholaminergic changes suggesting sympathetic overactivity.
      Finally distinct biochemical differences between patients with migraine without
      aura and patients with tension headache on one hand, and between patients with
      migraine with aura and patients with migraine without aura on the other hand will
      be emphasized. Findings in platelets will be discussed only if they are
      complementary and supportive to the plasma and urine data.

PMID- 1379707
TI  - The trigemino-vascular system and migraine.
AB  - Neurogenic inflammation has been proposed as a possible pathogenetic mechanism
      for migraine and cluster headache. Antidromic stimulation of trigeminal fibers
      causes plasma protein extravasation, mast cell activation and degranulation,
      vacuolation and increase in endothelial vesicle number within post capillary
      venules in rat dura mater. The antimigraine drugs sumatriptan and
      dihydroergotamine block the development of plasma extravasation and
      ultrastructural changes, as well as plasma calcitonin gene-related peptide (CGRP)
      increase in the superior sagittal sinus following electrical trigeminal ganglion
      stimulation. Sumatriptan and dihydroergotamine bind with high affinity to the 5
      HT1D/1B receptors, thus suggesting that their neurogenic antiinflammatory
      activity is mediated by activation of 5-HT autoreceptors present on sensory
      fibers innervating blood vessels in dura mater.

PMID- 1379708
TI  - The pathophysiology of migraine: a tentative synthesis.
AB  - It is proposed that the migraine attack is explicable by an interaction between
      the brain and the cranial circulation in subjects with unstable vascular and pain
      control mechanisms. While peptides are undoubtedly involved in vasodilatation,
      there is strong evidence that 5-HT plays an important part in the genesis of
      migraine. Whether the place of 5-HT lies in central pain-control pathways, in the
      serotonergic project to the cerebral cortex, in a direct action on the cranial
      blood vessels or in its action at all three sites remains uncertain. It seems
      probable that the primary action of sumatriptan or ergotamine in terminating
      migraine headache is exerted on the cerebral and extracranial circulation whereas
      medications employed in prophylaxis may act centrally.

PMID- 1379709
TI  - [Correlation between the nucleolar organizer region in adenocarcinoma of the
      prostate and the Gleason system].
AB  - Using a silver staining, technique, Nucleolar Organizer Region-associated
      proteins (NORs) were studied on paraffin sections of 25 resected prostatic
      adenocarcinomas classified with Gleason grading and 11 hyperplastic lesions. Then
      7 inclusions was selected for each grade of Gleason system and 7 inclusions of
      normal prostatic tissue. The mean numbers of argyrophilic nucleolar organizer
      regions (AgNORs) increased significantly (P less than 0.01) from normal prostatic
      tissue to Gleason 5. The data indicate that AgNORs counts may help distinguish
      between each grade of Gleason system. It was concluded that the AgNOR technique
      provides a significant kinetic evaluation of prostatic adenocarcinoma and its
      prognostic study.

PMID- 1379710
TI  - Fine needle aspiration biopsy cytology as an adjunct in the diagnosis of
      childhood sarcoidosis.
AB  - Fine needle aspiration biopsy cytology performed in three children with
      sarcoidosis expedited clinical investigation and diagnosis of their disease. Each
      patient had a different clinical presentation; in two of them lymphoma was part
      of the initial differential diagnosis. Aspiration cytology in all cases revealed
      collections of epithelioid histiocytes, and multinucleate foreign body-type giant
      cells, without accompanying necrosis or acute inflammation. A diagnosis of non
      caseating granulomas consistent with sarcoidosis was made in all aspirates.
      Special stains for identification of organisms performed on the smears of one
      case, and culture of aspirate material from one case were negative. Subsequent
      serum angiotensin converting enzyme levels in all patients were elevated. Chest x
      ray films in all patients showed mediastinal and hilar lymphadenopathy. One
      patient had an interstitial pulmonary infiltrate. All patients responded to
      steroid therapy. Fine needle aspiration biopsy can be a useful diagnostic tool in
      the evaluation of children with suspected sarcoidosis.

PMID- 1379711
TI  - Comparative investigations of the morphology and chemical composition of the
      eggshells of Acanthocephala. II. Palaeacanthocephala.
AB  - Eggshells of the palaeacanthocephalans Acanthocephalus anguillae, Pomphorhynchus
      laevis and Polymorphus minutus were investigated for their fine structure as well
      as their chemical composition. The acanthor larvae are surrounded by four
      eggshells (E1-E4) separated by interstices (G1-G4). Immature eggs do not exhibit
      the complete set of eggshells. The chemical composition of the outermost, thin
      eggshell (E1) remains unknown. E2 is supplied by outer filaments of different
      strength; it contains keratin, which was localized electron microscopically using
      anti-keratin. In P. laevis and P. minutus, E3 seems to contain glycoproteins,
      which could not be visualized in this eggshell of A. anguillae. The innermost
      eggshell (E4) uniformly contains chitin. The electron-lucent interstices of the
      eggs of P. laevis and P. minutus are rich in polysaccharides and/or
      proteoglycans, whereas those of A. anguillae contain low amounts of such
      substances. The differences observed in the abundance of carbohydrates are
      discussed with respect to the life cycles of the three acanthocephalans.

PMID- 1379712
TI  - A comparison of sporozoite and cyst merozoite surface proteins of Sarcocystis.
AB  - Surface labeling of Sarcocystis muris and S. suicanis sporozoites with N
      hydroxysuccinimide biotin led to the detection of major membrane proteins with
      relative molecular weights of 29 and 30 kDa, respectively. Immunoblots of
      Sarcocystis sporozoite proteins probed with sera from infected hosts or with
      polyclonal monospecific antibodies generated against membrane antigens of cyst
      merozoites (noncorresponding stages) showed cross-reactivity between the two
      developmental stages (cyst merozoites and sporozoites) as well as between the
      species S. muris and S. suicanis. Two-dimensional gel electrophoresis resulted in
      the identification of isoforms of the sporozoite membrane antigens, with
      isoelectric points ranging from pH 4.7 to pH 6.4 for S. muris and from pH 4.7 to
      pH 5.2 for S. suicanis. The molecular masses, the charge heterogeneity, and the
      immunological reactivity of the surface proteins of Sarcocystis sporozoites were
      similar to those of cyst merozoites of both species.

PMID- 1379713
TI  - Conditions affecting the immunohistochemical detection of HIV in fixed and
      embedded renal and nonrenal tissues.
AB  - A number of studies have suggested that HIV infection can be detected in a
      variety of routinely fixed archival tissues using antibodies to various viral
      proteins. In order to study this immunocytochemical approach, paraffin sections
      were examined with a large panel of commercially available monoclonal antibodies
      against the various HIV proteins (5 antibodies to p24, 1 to p17, 1 to gp41, and 1
      to gp120) using a streptavidin-biotin method. A polyclonal antibody against p24
      was also tested. Formalin-fixed, paraffin-embedded HIV infected CEM E5 T cells
      were used as positive controls. Tissues from AIDS patients included 31 kidneys, 8
      lymph nodes, 2 spleens and 3 brains. Non-AIDS tissues examined were 6 renal
      biopsies with focal segmental glomerulosclerosis, 5 with interstitial nephritis,
      6 reactive lymph nodes, and a brain with encephalitis, all from patients not
      known to be at high risk for HIV infection. Additional negative controls
      included: 1) replacement of primary antibody with a hybridoma derived mouse
      monoclonal IgG1 standard, 2) omission of the primary antibody, and 3) sections of
      formalin-fixed paraffin-embedded CEM E5 T cells cultures not infected with HIV.
      Competition experiments with excess recombinant p24 protein were also performed.
      False positive staining with the IgG1 standard or with the antibodies to HIV
      proteins was frequently seen in tissues with pathologic findings (inflammation,
      hyalin degeneration), particularly following protein digestion. Protein digestion
      also had a major impact on specific staining. Digestion with proteinase K
      abolished specific staining for the core proteins of the virus (p17, p24) on the
      positive control sections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379714
TI  - Chromosomes in the diagnosis of soft tissue tumors. I. Synovial sarcoma.
AB  - It has been established that nonrandom chromosome rearrangements are
      characteristic of specific types of neoplasia. We present six new cases of
      sarcoma that had in common the same chromosome abnormality, i.e., a balanced
      translocation between chromosomes X and 18, t(X;18)(p11.2;q11.2), and evaluate
      the 15 cases with this translocation in the literature. The histological
      diagnosis was synovial sarcoma in 19 cases and malignant fibrous histiocytoma and
      fibrosarcoma in the remaining two tumors, respectively. The translocation was
      found in tumors of both the biphasic and monophasic types, as well as in poorly
      differentiated synovial sarcoma. The two nonsynovial sarcomas with the t(X;18)
      were described as spindle cell tumors but failed to show the presence of
      cytokeratins by immunohistochemical stains. Even with the numerous variabilities
      on which this test depends, the cytogenetic analysis holds great promise as a
      tool for the diagnosis of synovial sarcoma.

PMID- 1379715
TI  - Lymphoid cells transformed by Abelson virus require the v-abl protein-tyrosine
      kinase only during early G1.
AB  - Cells infected with temperature-sensitive transformation mutants of the Abelson
      murine leukemia virus express low levels of kinase activity at the nonpermissive
      temperature, causing transformed pre-B cells to die under these conditions.
      Examination of cell cycle profiles of such populations prior to cell death
      reveals that the cells accumulate in the G1 phase of the cell cycle. Following G1
      arrest, the cells die via apoptosis, an active process of cell elimination. Cell
      synchronization and temperature-shift experiments show that G1 arrest reflects
      the requirement for a functional v-abl protein during early G1 and that the
      molecule is not required at other phases of the cell cycle. These data indicate
      that the substrate(s) critical to v-abl-mediated transformation is involved in
      regulating G1 transit and that these interactions are dominant over all other
      changes required for the multistep process that results in the fully malignant
      phenotype associated with v-abl expression in lymphoid cells.

PMID- 1379717
TI  - Cloning and expression of a Ca(2+)-inhibitable adenylyl cyclase from NCB-20
      cells.
AB  - A cDNA that encodes an adenylyl cyclase [ATP pyrophosphate-lyase (cyclizing), EC
      4.6.1.1] has been cloned from NCB-20 cells, in which adenylyl cyclase activity is
      inhibited by Ca2+ at physiological concentrations. The cDNA clone (5.8 kilobases)
      was isolated by polymerase chain reaction (PCR) using degenerate primers designed
      by comparison of three adenylyl cyclase sequences (types I, II, and III) and
      subsequent library screening. Northern analysis revealed expression of mRNA (6.1
      kilobases) corresponding to this cDNA in cardiac tissue, which is a prominent
      source of Ca(2+)-inhibitable adenylyl cyclase. The clone encodes a protein of
      1165 amino acids, whose hydrophilicity profile was very similar to those of other
      mammalian adenylyl cyclases that have recently been cloned. A noticeable
      difference between this protein and other adenylyl cyclases was a lengthy
      aminoterminal region before the first transmembrane span. Transient expression of
      this cDNA in the human embryonic kidney cell line 293 revealed a 3-fold increase
      in cAMP production in response to forskolin compared with control transfected
      cells. In purified plasma membranes from transfected cells, increased adenylyl
      cyclase activity was also detected, which was susceptible to inhibition by
      submicromolar Ca2+. Thus, this adenylyl cyclase seems to represent the Ca(2+)
      inhibitable form that is encountered in NCB-20 cells, cardiac tissue, and
      elsewhere. Its identification should permit a determination of the structural
      features that determine the mode of regulation of adenylyl cyclase by Ca2+.

PMID- 1379716
TI  - Cloned and expressed macrophage nitric oxide synthase contrasts with the brain
      enzyme.
AB  - Nitric oxide (NO) is a messenger molecule of macrophages, endothelial cells in
      blood vessels, and neurons. A neuronal form of NO synthase (NOS) has been
      previously cloned. We now report the molecular cloning of macrophage NOS. The
      macrophage enzyme displays 50% sequence identity to the neuronal enzyme. Like
      neuronal NOS, macrophage NOS has recognition sites for FAD, FMN, and NADPH and
      also has a consensus calmodulin binding site. Macrophage NOS mRNA is strikingly
      inducible; it is absent in quiescent macrophages or spleen but is prominent 2-6
      hr after endotoxin treatment.

PMID- 1379719
TI  - The partially folded conformation of the Cys-30 Cys-51 intermediate in the
      disulfide folding pathway of bovine pancreatic trypsin inhibitor.
AB  - The best-characterized protein folding pathway is that of bovine pancreatic
      trypsin inhibitor, which folds from the reduced form through a series of
      disulfide bond intermediates. The crucial one-disulfide intermediate of bovine
      pancreatic trypsin inhibitor with the disulfide bond between Cys-30 and Cys-51 is
      shown here to have a partially folded conformation in which the major elements of
      secondary structure interact via a core of apolar side chains, which resembles
      part of the native conformation. The stability of this structure can account for
      the predominance of this one-disulfide intermediate during folding. Much of the
      remaining one-third of the polypeptide chain, in particular the N-terminal 14
      residues, is largely disordered; this accounts for the ability of this
      intermediate to form readily any of the three possible second disulfide bonds
      involving Cys-5, -14, and -38. The partially folded conformation of this
      intermediate provides direct evidence for the importance of native-like
      interactions between elements of secondary structure in directing protein
      folding, which is assumed in many studies.

PMID- 1379718
TI  - Cloning and expression of a cAMP-activated Na+/H+ exchanger: evidence that the
      cytoplasmic domain mediates hormonal regulation.
AB  - The ubiquitous plasma membrane Na+/H+ exchanger (termed NHE1) is activated by
      diverse hormonal signals, with the notable exception of hormones acting through
      cAMP as second messenger. Therefore, the Na+/H+ exchanger found in the nucleated
      trout red cell is of particular interest since it is activated by catecholamines,
      forskolin, and cAMP analogues. We report here that a cloned cDNA encoding the red
      cell exchanger restores functional Na+/H+ activity when transfected into Na+/H+
      antiporter-deficient fibroblasts (i.e., it regulates intracellular pH in a Na
      dependent and amiloride-sensitive manner). This red cell exchanger represents an
      additional form of Na+/H+ exchanger (termed beta NHE), which is characterized by
      a specific cytoplasmic domain involved in activation by the cAMP-dependent
      signaling pathway. After transfection in the same cellular context, beta NHE, but
      not NHE1, is activated by cAMP or by hormones that increase cAMP levels.
      Comparison of the amino acid sequences of exchangers shows that beta NHE, but not
      NHE1, contains two clustered consensus motifs for phosphorylation by a cAMP
      dependent protein kinase (protein kinase A; PKA). A deletion mutant devoid of the
      C-terminal region of the cytoplasmic loop containing the two PKA sites restores
      Na+/H+ activity but is no longer activated by cAMP analogues or catecholamines.
      In red blood cells, the Na+/H+ exchanger is also activated by another pathway
      involving protein kinase C (PKC). Expression of beta NHE in fibroblasts shows
      that these two independent signaling pathways impinge on two distinct domains of
      the exchanger. The cytoplasmic segment containing PKA consensus sites, which is
      crucial for cAMP activation, is unnecessary for stimulation by PKC activators.

PMID- 1379720
TI  - Antisense oligodeoxynucleotides to the cystic fibrosis transmembrane conductance
      regulator inhibit cAMP-activated but not calcium-activated chloride currents.
AB  - Phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR)
      by cAMP-dependent protein kinase leads to chloride flux in epithelial cells. Is
      CFTR also required for the calcium-dependent activation of chloride channels? We
      used antisense oligodeoxynucleotides to CFTR to reduce the expression of CFTR in
      colonic and tracheal epithelial cells. The antisense oligomers were a pair of
      adjacent 18-mers complementary to nucleotides 1-18 and 19-36 of CFTR mRNA. Sense
      and misantisense oligomers served as controls. A 48-h antisense treatment reduced
      the expression of CFTR protein as assayed by immunoprecipitation and
      autoradiography to 26% of the level in sense-treated T84 cells. Whole-cell patch
      clamp revealed that a 48-h antisense treatment of T84 and 56FHTE-8o- fetal
      tracheal epithelial cells reduced the cAMP-activated chloride current to
      approximately 10% of that in sense-treated cells. The half-life of functional
      CFTR is less than 24 h in these cells. In contrast, the calcium-activated
      chloride current was not affected by antisense treatment. Hence, the cAMP and
      calcium pathways are separate. CFTR is required for the cAMP pathway but not for
      the calcium pathway.

PMID- 1379721
TI  - Presence of a member of the Tc1-like transposon family from nematodes and
      Drosophila within the vasotocin gene of a primitive vertebrate, the Pacific
      hagfish Eptatretus stouti.
AB  - Molecular cloning of the vasotocin gene of a cyclostome, the Pacific hagfish
      Eptatretus stouti, reveals, in contrast to other known members of the vertebrate
      vasopressin/oxytocin hormone gene family, an unusual exon-intron organization.
      Although the location of three exons and two introns is conserved, an additional
      intron is present 5' of the coding region of the hagfish gene. The third intron,
      which is greater than 14 kilobase pairs in size, contains on the opposite DNA
      strand to that encoding vasotocin an open reading frame exhibiting striking
      similarity to the putative transposase of Tc1-like nonretroviral mobile genetic
      DNA elements, so far reported only from nematodes and Drosophila. The hagfish
      element, called Tes1, is flanked by inverted terminal repeats representing an
      example of the existence of a typical inverted terminal-repeat transposon within
      vertebrates. The presence of Tc1-like elements in nematodes, Drosophila, and
      cyclostomes indicates that these genetic elements have a much broader
      phylogenetic distribution than hitherto expected.

PMID- 1379722
TI  - The yeast nuclear gene suv3 affecting mitochondrial post-transcriptional
      processes encodes a putative ATP-dependent RNA helicase.
AB  - Mitochondrial gene expression is controlled largely through the action of
      products of the nuclear genome. The yeast nuclear gene suv3 has been implicated
      in a variety of mitochondrial posttranscriptional processes and in translation
      and, thus, represents a key control element in nuclear-mitochondrial
      interactions. We have exploited a property of a mutant allele of suv3, SUV3-1,
      that causes, among other effects, a massive increase in the abundance of excised
      group I introns to clone the wild-type gene by a strategy of colony Northern
      hybridization. We have determined that the 84-kDa deduced protein product of the
      suv3 gene, which maps to chromosome XVI, has a typical mitochondrial targeting
      presequence and additional sequence motifs that suggest that it belongs to a
      family of ATP-dependent RNA helicases, enzymes whose importance in post
      transcriptional and translational events has recently become apparent. We have
      identified the SUV3-1 mutation as a G----T transversion that creates a Val----Leu
      substitution in a 10-amino acid block that is highly conserved among ATP
      dependent RNA helicases. We discuss some implications of this mutation on the
      effects of the SUV3-1 allele on mitochondrial RNA metabolism.

PMID- 1379723
TI  - Cone visual pigments are present in gecko rod cells.
AB  - The Tokay gecko (Gekko gekko), a nocturnal lizard, has two kinds of visual
      pigments, P467 and P521. In spite of the pure-rod morphology of the photoreceptor
      cells, the biochemical properties of P521 and P467 resemble those of iodopsin
      (the chicken red-sensitive cone visual pigment) and rhodopsin, respectively. We
      have found that the amino acid sequence of P521 deduced from the cDNA was very
      similar to that of iodopsin. In addition, P467 has the highest homology with the
      chicken green-sensitive cone visual pigment, although it also has a relatively
      high homology with rhodopsins. These results give additional strength to the
      transmutation theory of Walls [Walls, G. L. (1934) Am. J. Ophthalmol. 17, 892
      915], who proposed that the rod-shaped photoreceptor cells of lizards have been
      derived from ancestral cone-like photoreceptors. Apparently amino acid sequences
      of visual pigments are less changeable than the morphology of the photoreceptor
      cells in the course of evolution.

PMID- 1379724
TI  - Increasing binding affinity of agonists to glutamate receptors increases synaptic
      responses at glutamatergic synapses.
AB  - This study examined the relationship between the affinity of glutamate agonists
      for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors
      and the characteristics of the physiological responses elicited by endogenous
      activation of the AMPA receptors. We tested the effects of chaotropic ions on
      [3H]AMPA binding in synaptic membranes as well as on synaptic responses elicited
      in CA1 by electrical stimulation of the Schaffer/commissural pathway in the in
      vitro hippocampal slice preparation. Of the chaotropic ions tested, only
      perchlorate and thiocyanate produced large increases in [3H]AMPA binding to
      synaptic membranes. The effect was due to an increase in affinity for agonists,
      as shown by a shift of the displacement curves of 6-cyano-7-nitro[3H]-quinoxaline
      2,3-dione binding by AMPA or glutamate. The effect of thiocyanate on [3H]AMPA
      binding was extremely sensitive to temperature, as the binding was increased
      almost 10-fold at 0 degree C but only 2- to 3-fold at 35 degrees C. The effect of
      perchlorate was only weakly temperature dependent. Similarly, thiocyanate and
      perchlorate were the only chaotropic ions tested that increased the initial slope
      and amplitude of the extracellularly recorded potentials evoked in CA1 dendritic
      field. Both ions did not change paired-pulse facilitation, an index of
      transmitter release, or fiber volley amplitude, an index of afferent recruitment.
      The chaotropic ions had no significant effects on either [3H]glutamate binding to
      the N-methyl-D-aspartate receptor or N-methyl-D-aspartate receptor-mediated
      synaptic responses. Finally, the effect of perchlorate on synaptic responses was
      significantly reduced after induction of long-term potentiation. These results
      indicate that an increase in affinity of the AMPA receptors for their agonists
      results in increased synaptic responses and strongly suggest that characteristics
      of the AMPA receptor are modified following long-term potentiation.

PMID- 1379725
TI  - Large induction of keratinocyte growth factor expression in the dermis during
      wound healing.
AB  - Recent studies have shown that application of basic fibroblast growth factor
      (basic FGF) to a wound has a beneficial effect. However, it has not been assessed
      whether endogenous FGF also plays a role in tissue repair. In this study we found
      a 160-fold induction of mRNA encoding keratinocyte growth factor (KGF) 1 day
      after skin injury. This large induction was unique within the family of FGFs,
      since mRNA levels of acidic FGF, basic FGF, and FGF-5 were only slightly induced
      (2- to 10-fold) during wound healing, and there was no expression of FGF-3, FGF
      4, and FGF-6 detected in normal and wounded skin. High levels of FGF receptor 1
      and FGF receptor 2 mRNA and low levels of FGF receptor 3 mRNA were found in both
      normal and wounded skin. No change in the levels of these transcripts was
      detected during wound healing. In situ hybridization studies revealed highest
      levels of KGF mRNA expression in the dermis at the wound edge and in the
      hypodermis below the wound. In contrast, mRNA encoding the receptor of this
      growth factor (a splice variant of FGF receptor 2) was predominantly expressed in
      the epidermis. These results suggest that basal keratinocytes are stimulated by
      dermally derived KGF during wound healing and implicate a unique role of this
      member of the FGF family in wound repair.

PMID- 1379726
TI  - Transgenic mice expressing a mutant keratin 10 gene reveal the likely genetic
      basis for epidermolytic hyperkeratosis.
AB  - Epidermolytic hyperkeratosis (EH; previously called bullous congenital
      ichthyosiform erythroderma) is an autosomal dominant skin disease of unknown
      etiology, affecting approximately 1 out of 300,000 people. It is typified by
      hyperkeratotic scaliness, blistering due to cytolysis within suprabasal epidermal
      cells, and hyperproliferation in basal cells. Histologically, EH epidermis
      exhibits a thickened stratum corneum and granular layer, with enlarged and
      irregular-shaped cells. Ultrastructurally, only suprabasal layers are affected,
      with three major aberrancies: (i) tonofilament clumping, (ii) nuclei and
      keratohyalin granules of irregular shape and size, and (iii) cell degeneration.
      We have discovered that transgenic mice expressing a mutant keratin 10 gene have
      the EH phenotype, thereby suggesting that a genetic basis for human EH residues
      in mutations in genes encoding suprabasal keratins K1 and K10. In addition, we
      show that (i) stimulation of basal cell proliferation can arise from a defect in
      suprabasal cells, and (ii) distortion of nuclear shape or aberrations in
      cytokinesis can occur when an intermediate filament network is perturbed.

PMID- 1379727
TI  - Unequal human immunodeficiency virus type 1 reverse transcriptase error rates
      with RNA and DNA templates.
AB  - Sequence variation in the type 1 human immunodeficiency virus (HIV-1) results, in
      part, from inaccurate replication by reverse transcriptase. Although this enzyme
      is error-prone during synthesis in vitro with DNA templates, the fidelity of RNA
      dependent DNA synthesis relevant to minus-strand replication in the virus life
      cycle has not been examined extensively. In the present study, we have developed
      a system to determine the fidelity of transcription and reverse transcription and
      have used it to compare the fidelity of DNA synthesis by the HIV-1 reverse
      transcriptase with RNA and DNA templates of the same sequence. Overall, fidelity
      was several-fold higher with RNA than with DNA. Sequence analysis of mutants
      generated with the two substrates revealed that differences in error rates were
      substantial for specific errors. Fidelity with RNA was greater than 10-fold
      higher for substitution and minus-one nucleotide errors at five different
      homopolymeric positions. Because such errors likely result from template-primer
      slippage, this result suggests that misaligned intermediates are formed and/or
      used less frequently with an RNA template-DNA primer than with a DNA template-DNA
      primer. The results also suggest that HIV-1 reverse transcriptase synthesis with
      an RNA template-DNA primer was error-prone during incorporation of the first two
      nucleotides, perhaps due to aberrant enzyme-substrate interactions as synthesis
      initiates. The unequal error rates with RNA and DNA templates suggest that
      mistakes during minus- and plus-strand DNA synthesis may not contribute equally
      to the mutation rate of HIV-1. The data also provide estimates of substitution
      and frameshift error rates during transcription by T7 RNA polymerase.

PMID- 1379728
TI  - Elevated expression of monocyte chemoattractant protein 1 by vascular smooth
      muscle cells in hypercholesterolemic primates.
AB  - Atherosclerosis is marked by an overt inflammatory infiltrate, with enhanced
      recruitment of monocytes/macrophages observed in both human and experimental
      atherosclerosis. We previously determined that monocyte chemoattractant protein 1
      (MCP-1) accounts for virtually all of the chemotactic activity produced by
      vascular (aortic) smooth muscle cells in culture. We now report that arteries
      from a primate model of atherosclerosis with dietary-induced hypercholesterolemia
      exhibit increased levels of MCP-1 mRNA expression in vivo, whereas their normal
      counterparts demonstrate minimal MCP-1 expression. Furthermore,
      immunohistochemistry and in situ hybridization clearly indicate that the
      expression of MCP-1 protein and mRNA is in the smooth muscle cells of the medial
      layer of the artery and in monocyte-like and smooth muscle-like cells found in
      the overlying intimal lesion. These studies indicate that one of the responses to
      dietary hypercholesterolemia is the expression of MCP-1 by vascular smooth muscle
      cells. This expression, when augmented with other cellular and molecular factors,
      could significantly contribute to the recruitment of monocytes/macrophages to the
      vessel wall.

PMID- 1379729
TI  - A high-molecular-weight squid neurofilament protein contains a lamin-like rod
      domain and a tail domain with Lys-Ser-Pro repeats.
AB  - Previous studies have shown that two low molecular-weight neurofilament (NF)
      proteins (NF-60 and NF-70) from the squid Loligo pealei are translated from mRNAs
      that are splice variants of a single squid NF gene. In this study, we report the
      isolation and characterization of cDNA clones encoding a high-molecular-weight
      squid NF protein (NF-220), the mRNA of which derives from the same squid NF gene.
      All three proteins are identical in their amino-terminal and lamin-like rod
      domains but differ in their carboxyl-terminal tail regions. In contrast to the
      short tail domains of NF-60 and NF-70, the NF-220 protein has a longer tail
      domain containing an acidic cluster of amino acids immediately followed by
      repeated copies of the sequence motif Lys-Ser-Pro. The Lys-Ser-Pro domain is
      similar to that of mammalian medium NF (NF-M) and high NF (NF-H) proteins, where
      the serines are highly phosphorylated. Except for these Lys-Ser-Pro motifs, there
      is surprisingly little structural similarity between the squid NF-220 protein and
      mammalian NF-M and NF-H proteins. Furthermore, the location of introns in squid
      NF-220 protein shows that it is more closely related to nuclear lamins and type
      III intermediate-filament proteins than to vertebrate NF proteins.

PMID- 1379730
TI  - RNA pseudoknots that inhibit human immunodeficiency virus type 1 reverse
      transcriptase.
AB  - High-affinity ligands of the reverse transcriptase of human immunodeficiency
      virus type 1 (HIV-1) were isolated by the SELEX procedure (systematic evolution
      of ligands by exponential enrichment) from RNA populations randomized at 32
      positions. Analysis of these ligands revealed a pseudoknot consensus with primary
      sequence bias at some positions. We demonstrated that at least one of the ligands
      inhibits cDNA synthesis by HIV reverse transcriptase but fails to inhibit other
      reverse transcriptases. These experiments highlight the power of SELEX to yield
      highly specific ligands that reduce the activity of target proteins. Such ligands
      may provide therapeutic reagents for viral and other diseases.

PMID- 1379731
TI  - Identification of a mammalian gene structurally and functionally related to the
      CDC25 gene of Saccharomyces cerevisiae.
AB  - The yeast Saccharomyces cerevisiae CDC25 gene encodes a nucleotide-exchange
      factor (NEF) that can convert the inactive GDP-bound state of RAS proteins to an
      active RAS-GTP complex. CDC25 can activate the yeast RAS proteins as well as the
      human H-ras protein. CDC25 is a member of a family of yeast genes that likely
      encode NEFs capable of regulating the RAS-related proteins found in yeast. By
      aligning the amino acid sequence of CDC25-related gene products we found a number
      of conserved motifs. Using degenerate oligonucleotides that encode these
      conserved sequences, we have used polymerase chain reactions to amplify fragments
      of mouse and human cDNAs related to the yeast CDC25 gene. We show that a chimeric
      molecule, part mouse and part yeast CDC25, can suppress the loss of CDC25
      function in the yeast S. cerevisiae.

PMID- 1379732
TI  - Design of peptide-acridine mimics of ribonuclease activity.
AB  - A series of peptide-acridine conjugates was designed and synthesized, based on
      three features of the proposed catalytic mechanism of RNase A: 2'-proton
      abstraction by His-12, proton donation to the leaving 5'-oxygen by His-119, and
      stabilization of the pentacoordinated phosphorous transition state by Lys-41. The
      substrate binding capability of RNase A was mimicked by the intercalator,
      acridine. Lysine served as a linker between acridine and the catalytic
      tripeptide. Cleavage of target RNA was monitored by agarose gel electrophoresis
      and by gel-permeation chromatography. The carboxyl-amidated conjugates HGHK(Acr)
      NH2, HPHK(Acr)-NH2, and GGHK(Acr)-NH2 (where Acr indicates 2-methyl-9
      acridinemethylene) all had similar hydrolytic activity. The catalytic mechanism
      most likely involved only the abstraction of the 2'-proton and stabilization of
      the transition state. These RNase mimics utilized rRNA and single-stranded RNA
      but not double-stranded RNA and tRNA as substrates.

PMID- 1379733
TI  - Central role for differential gene expression in mammalian hibernation.
AB  - Mammalian hibernators experience dramatic reductions in body temperature,
      metabolic rate, respiratory rate, and heart rate during hibernation. These
      changes are precisely controlled and reversible with only internally driven
      mechanisms, suggesting specific biochemical regulation. We present a model that
      integrates our observations of differential liver gene expression during
      preparation for, and maintenance of, the hibernating state, with the known
      phylogenetic interspersion of hibernating species in several major mammalian
      lineages. This model predicts a major role for the differential expression of
      existing mammalian genes in the biochemical regulation of hibernation.

PMID- 1379734
TI  - copia-like retrotransposons are ubiquitous among plants.
AB  - Transposable genetic elements are assumed to be a feature of all eukaryotic
      genomes. Their identification, however, has largely been haphazard, limited
      principally to organisms subjected to molecular or genetic scrutiny. We assessed
      the phylogenetic distribution of copia-like retrotransposons, a class of
      transposable element that proliferates by reverse transcription, using a
      polymerase chain reaction assay designed to detect copia-like element reverse
      transcriptase sequences. copia-like retrotransposons were identified in 64 plant
      species as well as the photosynthetic protist Volvox carteri. The plant species
      included representatives from 9 of 10 plant divisions, including bryophytes,
      lycopods, ferns, gymnosperms, and angiosperms. DNA sequence analysis of 29 cloned
      PCR products and of a maize retrotransposon cDNA confirmed the identity of these
      sequences as copia-like reverse transcriptase sequences, thereby demonstrating
      that this class of retrotransposons is a ubiquitous component of plant genomes.

PMID- 1379735
TI  - Levels of mRNA coding for motoneuron growth-promoting factors are increased in
      denervated muscle.
AB  - Partial denervation of skeletal muscle induces sprouting of axons remaining
      within the muscle, possibly as a result of increased synthesis by denervated
      muscle fibers of motoneuron growth-promoting factors. Direct verification of this
      hypothesis has not been possible because the molecules responsible are not
      unambiguously characterized. We used Xenopus oocytes as a functional assay for
      mRNAs coding for secreted growth factors: preparations of mRNA from innervated
      and denervated neonatal muscle were injected into oocytes. Three days later,
      oocytes injected with denervated muscle mRNA expressed increased levels of
      nicotinic acetylcholine receptor and voltage-dependent sodium channels at their
      membrane. Proteins secreted by the same oocytes were tested for their effects on
      (i) neurite outgrowth from embryonic chicken ventral spinal cord neurons; (ii)
      survival in mixed culture of embryonic chicken motoneurons identified using the
      SC1 antibody; and (iii) survival of embryonic motoneurons purified by panning on
      SC1 antibody. In all three assays, media conditioned by oocytes injected with
      mRNA from denervated muscle contained significantly higher levels of biological
      activity than did those from oocytes injected with innervated muscle mRNA or
      water. mRNA was prepared from muscle at different times after denervation: a
      maximal increase was obtained already after 1 day, consistent with an involvement
      in sprouting. Synthesis of motoneuron growth-promoting factors is thus regulated
      by denervation in a parallel fashion to that of other key components of the
      neuromuscular junction.

PMID- 1379736
TI  - Role of p34cdc2-mediated phosphorylations in two-step activation of pp60c-src
      during mitosis.
AB  - Phosphorylation of pp60c-src by p34cdc2 at three amino-proximal serine/threonine
      residues is temporally correlated with, but insufficient for, mitotic activation
      of c-Src kinase. The direct cause of activation during mitosis appears to be
      temporally correlated partial dephosphorylation of Tyr-527, a residue whose
      phosphorylation strongly suppresses pp60c-src activity. Site-directed mutagenesis
      of the serine/threonine phosphorylation sites blocks half the mitosis-specific
      decrease in Tyr-527 phosphorylation and half the increase in pp60c-src kinase
      activity. We conclude that p34cdc2 partially activates pp60c-src by a two-step
      process in which its serine/threonine phosphorylations either sensitize pp60c-src
      to a Tyr-527 phosphatase or desensitize it to a Tyr-527 kinase. Furthermore,
      additional events, independent of these p34cdc2-mediated phosphorylations,
      participate in mitotic activation of pp60c-src.

PMID- 1379737
TI  - The glial voltage-gated sodium channel: cell- and tissue-specific mRNA
      expression.
AB  - Previous electrophysiological and pharmacological studies on central and
      peripheral glia revealed the presence of voltage-gated Na channels with
      properties that are similar but not identical to those of neuronal Na channels.
      Here we report the isolation and characterization of a cDNA encoding the C
      terminal portion of a putative glial Na-channel (Na-G) alpha subunit. The amino
      acid sequence deduced from this cDNA indicates that the Na-G represents a
      separate molecular class within the mammalian Na-channel multigene family. By
      Northern blot, RNase protection, and in situ hybridization assays, we demonstrate
      that, in addition to brain astroglia, the Na-G mRNA is expressed in cultures of
      Schwann cells derived from dorsal root ganglia or from sciatic nerve. In vivo,
      the Na-G mRNA is detected not only in brain, dorsal root ganglia, and sciatic
      nerve, but also in tissues outside the nervous system including cardiac and
      skeletal muscle and lung. Its level varies according to the tissue and is
      developmentally regulated. The sequence and expression data concur in designating
      Na-G as an distinct type of Na channel, presumably with low sensitivity to
      tetrodotoxin.

PMID- 1379738
TI  - [Atypical verbal behavior in a 30 year follow-up of an acquired aphasia-epilepsy
      syndrome].
AB  - Detailed study of the communication of one of the patients followed-up by Deonna
      et al. (1989) who has been suffering since age seven of an atypical acquired
      aphasia-epilepsia syndrome. Seizures as well as peculiar verbal productions
      persist at adult age. After a thirty year follow-up, only a small lexicon has
      been acquired, mostly made of onomatopeia and idiosyncrasies. We describe this
      lexicon and discuss the quality of the communication in a real-life ecological
      situation. We then compare it to the jargon and the aphasic productions of the
      standard neuropsychological examination.

PMID- 1379739
TI  - Early manifestations of dementing illness: treatment with glycosaminoglycan
      polysulfate.
AB  - 1. In a multicenter, placebo-controlled, double-blind clinical trial in 156
      elderly patients with psychopathologic symptoms, glycosaminoglycan polysulfate
      was found to be a therapeutically effective agent in the treatment of the
      earliest manifestations of a dementing process. 2. Treatment with
      glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the
      basis of a divided dosage schedule for 24 weeks, was significantly superior to an
      inactive placebo on several outcome measures including the SCAG Total and factor
      scores (i.e., Cognitive Dysfunction, Withdrawal, Agitation/Irritability and
      Depression), the NOWLIS Total and Fatiguability factor scores, the MMSE, the HAM
      D Total and Vegetative Symptoms factor score and the CGI Severity of Illness and
      Global Improvement. 3. The drug was well tolerated; vital signs and laboratory
      measures did not show clinically significant changes within the experimental
      period.

PMID- 1379740
TI  - Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in
      localized, inoperable carcinoma of the esophagus. A prospective randomized
      multicentre study: the second Scandinavian trial in esophageal cancer.
AB  - Survival and swallowing function were studied in a randomized trial of 97
      patients with inoperable, localized esophageal carcinoma. Radical radiotherapy
      was given to 51 patients, while 46 patients had two courses of
      bleomycin/cisplatin before radiotherapy. The survival was 29% after one year, and
      6% after 3 years in the radiotherapy group. The survival in the combined
      treatment group was 18 and 0%, respectively; p = 0.1895. The number of patients
      who could swallow any food increased from 6% before treatment to 38% after 3
      months in the radiotherapy group, and from 0% to 23% in the combined group. No
      benefit was found by combining bleomycin/cisplatin with radiotherapy.

PMID- 1379741
TI  - [Stomach carcinoma: surgical strategy and therapy results 1992].
AB  - Surgical strategy for gastric carcinoma consists in total gastrectomy as a rule
      combined with extended lymphadenectomy. In small tumors of the intestinal type
      located in the distal stomach distal gastric resection can be taken into
      consideration. In case of high risk patients endoscopic polypectomy of a polypoid
      early gastric carcinoma can be sufficient. If the operation is done for cure we
      perform intraoperative radiotherapy within a prospective trial. For palliative
      situations procedures including removal of the tumor have better results with
      regard to quality of life and survival than bypass methods.

PMID- 1379742
TI  - Chloride-dependent cation conductance activated during cellular shrinkage.
AB  - A chloride (Cl-)-dependent, nonselective cation conductance was activated during
      cellular shrinkage and inhibited during cellular swelling or by extracellular
      gadolinium. The shrinking-induced, nonselective cation conductance and the
      swelling-induced anion conductance appear to function in the regulation of cell
      volume in airway epithelia. The shrinking-induced cation conductance had an
      unusual dependence on Cl-: partial replacement of extracellular Cl- with
      aspartate reduced the magnitude of the shrinking-enhanced current without
      accompanying changes in the reversal potential. The Cl- dependence of the
      nonselective cation conductance could provide a mechanism that tightly regulates
      Cl- secretion and sodium reabsorption in cells under osmotic stress.

PMID- 1379743
TI  - Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to
      86.5 minutes.
AB  - The DNA sequence of 91.4 kilobases of the Escherichia coli K-12 genome, spanning
      the region between rrnC at 84.5 minutes and rrnA at 86.5 minutes on the genetic
      map (85 to 87 percent on the physical map), is described. Analysis of this
      sequence identified 82 potential coding regions (open reading frames) covering 84
      percent of the sequenced interval. The arrangement of these open reading frames,
      together with the consensus promoter sequences and terminator-like sequences
      found by computer searches, made it possible to assign them to proposed
      transcriptional units. More than half the open reading frames correlated with
      known genes or functions suggested by similarity to other sequences. Those
      remaining encode still unidentified proteins. The sequenced region also contains
      several RNA genes and two types of repeated sequence elements were found.
      Intergenic regions include three "gray holes," 0.6 to 0.8 kilobases, with no
      recognizable functions.

PMID- 1379744
TI  - The skeletal muscle chloride channel in dominant and recessive human myotonia.
AB  - Autosomal recessive generalized myotonia (Becker's disease) (GM) and autosomal
      dominant myotonia congenita (Thomsen's disease) (MC) are characterized by
      skeletal muscle stiffness that is a result of muscle membrane hyperexcitability.
      For both diseases, alterations in muscle chloride or sodium currents or both have
      been observed. A complementary DNA for a human skeletal muscle chloride channel
      (CLC-1) was cloned, physically localized on chromosome 7, and linked to the T
      cell receptor beta (TCRB) locus. Tight linkage of these two loci to GM and MC was
      found in German families. An unusual restriction site in the CLC-1 locus in two
      GM families identified a mutation associated with that disease, a phenylalanine
      to-cysteine substitution in putative transmembrane domain D8. This suggests that
      different mutations in CLC-1 may cause dominant or recessive myotonia.

PMID- 1379745
TI  - Identification of a protein that binds to the SH3 region of Abl and is similar to
      Bcr and GAP-rho.
AB  - A Src homology 3 (SH3) region is a sequence of approximately 50 amino acids found
      in many nonreceptor tyrosine kinases and other proteins. Deletion of the SH3
      region from the protein encoded by the c-abl proto-oncogene activates the
      protein's transforming capacity, thereby suggesting the participation of the SH3
      region in the negative regulation of transformation. A complementary DNA was
      isolated that encoded a protein, 3BP-1, to which the SH3 region of Abl bound with
      high specificity and to which SH3 regions from other proteins bound
      differentially. The sequence of the 3BP-1 protein is similar to that of a COOH
      terminal segment of Bcr and to guanosine triphosphatase-activating protein (GAP)
      rho, which suggests that it might have GAP activity for Ras-related proteins. The
      3BP-1 protein may therefore be a mediator of SH3 function in transformation
      inhibition and may link tyrosine kinases to Ras-related proteins.

PMID- 1379746
TI  - From DSM-I to III-R; voices of self, mastery and the other: a cultural
      constructivist reading of U.S. psychiatric classification.
AB  - The continual process of mental disease classification in U.S. psychiatry is
      assumed to reflect advancing professional knowledge of these disorders. To date,
      the American Psychiatric Association has developed four standard classifications,
      or nosologies, called Diagnostic and Statistical Manuals ('DSMs'). DSM-I, the
      earliest, appeared in 1952 while the most recent, DSM-III-R, appeared in 1987.
      This paper employs a cultural constructivist perspective to deconstruct these
      nosologies and the classificatory process itself. Constructivism's premises,
      which emphasize culture, history, meaning and the constructed nature of medical
      phenomena, serve as the framework for the analysis. The paper shows that
      professional psychiatric classification expresses an underlying cultural
      psychology which encompasses four phenomenological domains and one of three
      Western person conceptions. Classifications are found to be explorations of
      culturally meaningful etiologies that explain the absence of 'self control', a
      central ethnopsychological aspect of the idealized self. Consideration of the
      vantage point of the voice of classification indicates that the ideal self is
      gender- (male), ethnic- (German Protestant) and age-specific (adult). The ethnic
      self's essence, and that of the Other, is believed to be biological, itself
      assumed to be natural and beyond culture or bias. Consequently, the
      ethnopsychology constructs as biologically caused the real and imagined
      differences in the gender, age or culturally Other. This invidious
      ethnobiological essentialism acts to create and maintain self-worth through a
      radical differentiation of self from those represented as Other.

PMID- 1379747
TI  - Prostate specific antigen levels during and after external beam radiotherapy for
      localized carcinoma of the prostate: predictor of therapeutic efficacy.
AB  - For 105 patients with locoregional carcinoma of the prostate, prostate specific
      antigen (PSA) levels were evaluated before, during and after external beam
      radiotherapy. The median follow-up is 17 months. In 51 patients (48.5%) initial
      PSA levels exceeded the maximum normal value of 20 ng/ml. Nine patients kept non
      declining high levels just after radiotherapy. Only one of these is free of
      disease. Assuming PSA levels decrease exponentially during radiotherapy, a mean
      half-life of 62 days (median 54, SD 26 days) was calculated. Three out of five
      patients with a PSA half-life of more than 88 days relapsed as compared to a 8%
      (3/37) relapse rate in patients with a "normal" half-life. Prolonged PSA half
      life suggests residual disease. PSA levels are expected to further decrease after
      radiation. Six months after irradiation persistent high PSA levels were found in
      14/51 (27.5%) patients. Only four of them had no evidence of manifest disease.
      Important negative prognostic factors for disease control in our series were non
      declining high levels of PSA, a PSA serum half-life exceeding 88 days and
      persistence of elevated PSA values longer than six months after treatment. In our
      opinion, PSA is a valuable marker in the follow-up of prostate cancer patients
      during and after radiotherapy.

PMID- 1379748
TI  - [Rapeseed poisoning of wild herbivores].
AB  - Beginning with the simultaneous occurrence of the first extensive sowing of 00
      rape and local increased losses among hares and roe deer in Western Germany and
      Austria at the end of 1986, the clinical and morphological symptoms of rape
      poisoning are discussed. They consist of damage to endo- and epithelium, cell
      membranes, blood, liver and in the so called "rape-blindness". Subsequently, the
      most important toxic agents of rape including their metabolites are presented.
      They consist in alkenyl- and indolyl-glucosinolates, leading to isothiocyanates
      (mustard oils), thiocyanates or thiocyanate ions resp., nitriles and antithyroid
      agents (e.g. goitrin) as well as S-methylcysteine sulphoxide and its metabolites,
      particularly dimethyl disulphide. Finally, the activity spectrum of the toxic
      agents or the metabolites and the clinical picture of the affected wildlife in
      1986 are compared with the result that the losses of that period are most likely
      to be traced back to rape poisoning and that the rape-blindness mentioned is to
      be interpreted as a thiocyanate-psychosis.

PMID- 1379749
TI  - FK506: inhibition of humoral mechanisms of hepatic allograft rejection.

PMID- 1379750
TI  - Simultaneous and quantitative isolation of nuclear and cytoplasmic RNA from
      eukaryotic cells.

PMID- 1379751
TI  - Effect of mismatching serologically defined residues on kidney transplant
      survival.
AB  - Amino acids within the HLA class I and II molecules were first examined
      individually for correlation with antibody reactions of over 50,000 antisera. The
      amino acids that correlated with the serologic reactions were classified as
      serologically defined: approximately half of the amino acids fell within that
      category, and the other half were employed as controls. The cadaver donor kidney
      transplant survival for patients who were mismatched for each of the sera-defined
      amino acids were compared to mismatches of the nonserologically defined amino
      acids. No differences were noted in the graft survivals of patients with
      mismatches for the serologically defined amino acids of HLA-A, -B, and -DR loci
      and for the nonserologically defined amino acids. Since many of the patients also
      had additional amino acids of mismatch, we cannot yet conclude that the
      serologically defined amino acids do not significantly influence graft outcome.
      In other words, the test may not have been sensitive enough to detect the degree
      of immunogenicity that may exist. However, we can conclude that mismatches for no
      single amino acid are strongly immunogenic.

PMID- 1379752
TI  - In situ cooling with use of a new trypsin inhibitor and hydroxyethyl starch in
      canine pancreaticoduodenal transplantation from non-heart-beating donors.

PMID- 1379754
TI  - Abdominal organ cluster transplantation in pigs receiving FK 506.

PMID- 1379753
TI  - Effectiveness of triple drug immunosuppression for pancreaticoduodenal
      allotransplantation in dogs.

PMID- 1379755
TI  - A comparative study of cyclosporine vs FK 506: role of kidney microsomal
      cytochrome P-450.

PMID- 1379756
TI  - FK 506-induced juxtaglomerular apparatus hyperplasia and tubular damage in rat
      kidney--morphologic and biologic analysis.

PMID- 1379757
TI  - Optimal dose of FK 506 in canine lung allotransplantation.

PMID- 1379758
TI  - Combination use of suboptimal doses of FK 506 and cyclosporine in canine lung
      transplantation.

PMID- 1379759
TI  - Low-dose of FK 506 and associated blood levels in allotransplantation of rat
      liver, heart, and skin.

PMID- 1379760
TI  - DNA analysis of peripheral blood mononuclear cells for early detection of hepatic
      graft rejection.

PMID- 1379761
TI  - FK 506 suppresses class II antigen expression in regenerating livers following
      partial hepatectomy in the rat.

PMID- 1379762
TI  - Immunosuppressive macrolides.

PMID- 1379763
TI  - Prevalence of hemoglobinopathies in north Jordan.
AB  - Blood samples from 1,000 subjects, 2-80 years old, were tested to explore the
      prevalence of alpha-thalassemia trait, high persistent HbF (HPFH), sickle cell
      trait and beta-thalassemia minor in northern Jordan. Hematological parameters and
      hemoglobin electrophoresis were carried out on all samples. Results showed 10
      (1%) subjects were sickle cell trait, 35 (3.5%) were heterozygous beta
      thalassemia, 31 (3.1%) alpha thalassemia trait and 10 (1%) high persistent HbF.
      The prevalence rates were different from those reported in neighbouring countries
      and their significance is discussed. No other abnormal hemoglobin types were
      observed.

PMID- 1379764
TI  - [Herpes simplex virus in Behcet's disease and in systemic diseases].

PMID- 1379765
TI  - Purification of larval Taenia solium antigens by gel filtration.
AB  - Crude larval Taenia solium extracts were fractionated by Sephacryl S-200 gel
      filtration into four fractions (W1-W4). The sensitivities of the fractions to
      rabbit and pig antiserum against Taenia solium were tested by double
      immunodiffusion, immunoelectrophoresis, and ELISA. Fraction W2 which was highly
      sensitive to antisera was shown by immunoblotting to contain antigen B (95 and
      105 kDa). The four fractions were shown to contain antigenic determinants common
      with pig serum proteins and crude extracts of other Platyhelminthes (especially
      Taenia hydatigena). Fraction W2 has the potential to be used as a serodiagnostic
      antigen.

PMID- 1379766
TI  - Variation amongst the neutralizing epitopes of bluetongue viruses isolated in the
      United States in 1979-1981.
AB  - Neutralizing epitopes present on field isolates of bluetongue virus (BTV)
      serotypes 10, 11, 13 and 17 were evaluated with a panel of polyclonal and
      neutralizing monoclonal antibodies (MAbs). A total of 91 field isolates were
      evaluated, including 15 isolates of BTV-10, 29 isolates of BTV-11, 26 isolates of
      BTV-13, and 21 isolates of BTV-17. The viruses were isolated from cattle, goats,
      sheep, elk and deer in Idaho, Louisiana, Nebraska and, predominantly, California,
      in the years 1979, 1980 and 1981. The isolates were analyzed and compared using a
      panel of neutralizing MAbs which included five MAbs raised against BTV-2, seven
      against BTV-10, five against BTV-13, and six against BTV-17. Neutralization
      patterns obtained with the MAb panel and individual field isolates were compared
      to those obtained with prototype viruses of each serotype. All field isolates
      were neutralized by at least some of the MAbs raised against the prototype virus
      of the same serotype. All field isolates of BTV-10 were neutralized by the seven
      MAbs raised to BTV-10, whereas the field isolates of BTV-11, BTV-13 and BTV-17
      were not consistently neutralized by all of the MAbs raised against the prototype
      virus of the same serotype. Variation in neutralizing epitopes recognized by the
      MAb panel was most pronounced amongst the field isolates of BTV-17. A one-way
      cross neutralization was evident between BTV-10 and BTV-17 as all field isolates
      of BTV-17 were neutralized by four of the MAbs raised against BTV-10. In
      contrast, no BTV-10 isolates were neutralized by the MAbs raised against BTV-17.
      Differences in the MAb neutralization patterns of field isolates of BTV-11, BTV
      13 and BTV-17 suggest that the immunogenic domain responsible for their
      neutralization is plastic, such that individual epitopes within the domain may
      vary in their significance to the neutralization of different viruses, even of
      the same serotype. The apparent conservation of neutralizing epitopes on field
      isolates of BTV-10 suggests that the field isolates may be derived from the
      modified-live vaccine strain of BTV-10.

PMID- 1379768
TI  - [Stomach cancer in pregnancy].
AB  - The presented clinical course of a 40 year old Primipara, in whom gastric cancer
      during pregnancy occurred, demonstrates the difficulties of differential
      diagnosis in early stages of the disease because of the non specific symptoms at
      that time. Mostly, they are related to physiological pregnancy associated
      complaints. Therefore, diagnosis is very often obtained lately and connected with
      advanced clinical stages of the tumor, which causes the bad survival rates of 10
      20% of these young women.

PMID- 1379767
TI  - Polymorphonuclear neutrophil leukocyte function in clinical bovine patients and
      in cows with or without Staphylococcus aureus mastitis.
AB  - A fluorochrome microassay was used to investigate peripheral blood
      polymorphonuclear leukocyte (PMNL) function in cattle. Glass-adherent PMNL were
      reacted with Staphylococcus aureus preincubated in 20% bovine serum for 30, 60
      and 90 min. Coverslips were stained with acridine orange (AO) followed by crystal
      violet to quench extracellular bacterial fluorescence. PMNL function was
      evaluated by counting the number of dead (stained red with AO) and live (stained
      green with AO) S. aureus contained within 100 PMNL. A phagocytic index was
      calculated as the average number of bacteria contained within PMNL. The
      percentage killing of S. aureus was calculated from the average proportion of S.
      aureus within PMNL that were dead. Six clinically normal Holstein calves, 3-4
      months of age, were sampled on 6 consecutive days. PMNL phagocytosis and killing
      did not vary significantly (p greater than 0.05) among repeated samplings per
      calf. PMNL function increased with increasing time of incubation of PMNL with S.
      aureus. Means (+/- SD) for percentage killing were 46.7 +/- 13.1, 57.4 +/- 11.6,
      and 62.1 +/- 9.8% for 30, 60 and 90 min of reaction, respectively. Means (+/- SD)
      for the phagocytic index were 2.9 +/- 0.8, 3.6 +/- 1.0, and 4.2 +/- 1.1
      bacteria/PMNL for 30, 60 and 90 min of reaction, respectively. PMNL function was
      determined in 30 normal cattle of various breeds, age and sex, and these values
      were pooled to provide normal values for PMNL function. When values for bovine
      clinical patients (n = 25) with various diagnoses were compared with normal
      values (defined by the mean +/- 2SD for the 30 normal cattle) for PMNL function,
      only one patient was observed to exhibit PMNL hypofunction. A cow with
      disseminated intravascular coagulation in association with peracute coliform
      mastitis exhibited decreased PMNL killing capacity. Abnormal PMNL function was
      uncommon in the hospital population studied. Peripheral blood PMNL function was
      evaluated in lactating Holstein cows with (n = 15) or without (n = 15) chronic
      subclinical S. aureus mastitis. There was no significant (p greater than 0.05)
      difference in PMNL function among these cows.

PMID- 1379769
TI  - [Prenatal serum screening for Down's syndrome].
AB  - With the aid of two commercially available analysis programmes we effected non
      invasive assessment of the risk for Down's syndrome in 597 pregnancies with
      healthy fetuses and in 22 pregnancies with trisomie 21-affected fetuses, maternal
      age ranging between 18 and 45 years. Based on the women's serum levels, hormone
      concentrations of AFP, free estriol and beta HCG were determined, a multiple of
      their median was combined with the age factor, and the result used as a parameter
      for overall risk estimation. A risk cut-off-level greater then 1:250 was
      considered to represent a positive risk. For patients younger than 35 years test
      sensitivity, at just over 50%, was found to be low. For those aged 35 years or
      greater, however, the Dermalog programme was able to detect 94.4% and the Alpha
      programme 88.2% of fetuses affected by trisomy 21, with a false-positive rate of
      19.6 and 19.1%, respectively. If the test were to be applied to all pregnant
      women beyond 35 years of age the detection rate of Down's syndrome could be
      nearly doubled compared to today's figure (only 50%, of women in this age group
      undergo amniocentesis). By the same token the rate of amniocentesis-induced
      abortion (approx. 1%) could be reduced to about one third.

PMID- 1379771
TI  - [An assessment of the status of natural foci of Crimean-Congo hemorrhagic fever
      in the Crimea].
AB  - The parasitological data and the results of the virological and serological
      investigations of materials, collected in nature and in the course of study of
      the immune structure of the population, are indicative of the circulation of CHF
      virus in the Crimea and the possibility of human infection. Data on spontaneous
      infection of four species of Ixodes ticks with CHF virus have been confirmed,
      including the data, obtained for the first time for this region, on the
      participation of Dermacentor marginatus in this process. The study has revealed,
      also for the first time, that, together with European brown hares, the natural
      foci of this infection may be maintained by scilly shrews, common voles and
      European wood mice. Low activity of the Crimean focus may be the result of active
      land reclamation, keeping the cattle stalled in most of the stock-breeding farms
      of the region, as well as a sharp decline in the number of hares at the
      territories of hunting preserves.

PMID- 1379770
TI  - [The dynamics of latent inhibition in rats under the action of substance P].
AB  - The role of substance P in latent inhibition was studied in experiments on rats.
      Administration of neuropeptide during pre-exposition of conditioned stimulus and
      before conditioning disturbed all signs of latent inhibition: level of
      reproduction, retention and resistance to amnestic action of conditioned reaction
      in the task of passive avoidance. Single administration of haloperidol before
      learning prevented the disturbance. Significance of hyperfunction of substance P
      in selective attention and pathogenesis of schizophrenia is discussed.

PMID- 1379772
TI  - [The improvement of the immunodiagnosis of para-influenza infection based on
      erythrocyte reagents].
AB  - Study of different methods of hemosensitization helped detect the optimum
      technology for the preparation of parainfluenza (type 3) antigenic erythrocyte
      diagnosticum. This technology ensures the highest sensitivity, specificity,
      economy (with respect to viral antigen consumption) and stability of the reagent.
      Titration of antibodies by means of the new diagnosticum and the detection of
      parainfluenza cases among children with acute respiratory virus infections, acute
      and chronic glomerulonephritis have been highly effective, considerably more
      effective than similar determinations by the hemagglutination inhibition test.

PMID- 1379773
TI  - [The capacity of purified staphylococcal anatoxin to correct antigen-specific and
      antigen-nonspecific immunological defects].
AB  - Purified staphylococcal toxoid is capable of partially preventing the development
      of antigen-specific (induced by the supraoptimal dose of sheep red blood cells)
      and antigen-nonspecific (induced by Tahyna virus) defects of humoral immune
      response, as well as abolishing these defects. The presence and manifestation of
      the correction of virus-induced immunodeficiency is determined by the dose of the
      toxoid and the interval between the injections of purified staphylococcal toxoid
      and the infective agent.

PMID- 1379774
TI  - Molecular definition of the smallest region of deletion overlap in the Wolf
      Hirschhorn syndrome.
AB  - Wolf-Hirschhorn syndrome (WHS), associated with a deletion of chromosome 4p, is
      characterized by mental and growth retardation and typical facial dysmorphism. A
      girl with clinical features of WHS was found to carry a subtle deletion of
      chromosome 4p. Initially suggested by high-resolution chromosome analysis, her
      deletion was confirmed by fluorescence in situ hybridization (FISH) with cosmid
      probes, E13 and Y2, of D4S113. To delineate this 4p deletion, we performed a
      series of FISH and pulsed-field gel electrophoresis analyses by using probes from
      4p16.3. A deletion of approximately 2.5 Mb with the breakpoint at approximately
      80 kb distal to D4S43 was defined in this patient and appears to be the smallest
      WHS deletion so far identified. To further refine the WHS critical region, we
      have studied three unrelated patients with presumptive 4p deletions, two
      resulting from unbalanced segregations of parental chromosomal translocations and
      one resulting from an apparently de novo unbalanced translocation. Larger
      deletions were identified in two patients with WHS. One patient who did not
      clinically present with WHS had a smaller deletion that thus eliminates the
      distal 100-300 kb from the telomere as being part of the WHS region. This study
      has localized the WHS region to approximately 2 Mb between D4S43 and D4S142.

PMID- 1379775
TI  - Effect of the c-kit codon 584 Phe----Leu substitution demonstrated in human
      piebaldism.

PMID- 1379776
TI  - Congenital deficiency of alpha-fetoprotein.
AB  - Although alpha-fetoprotein may play a role in fetal immune function or in
      maintenance of osmotic pressure, its exact function is unknown. We report two
      infants documented to have congenital deficiency of alpha-fetoprotein. One infant
      had cord blood levels less than 0.5 ng/ml. The second infant had a neonatal level
      of 120 ng/ml, which is about 2% of the usual concentration for a term newborn.
      These infants document the existence of congenital deficiency of serum alpha
      fetoprotein. Because it is homologous to albumin, congenital deficiency of alpha
      fetoprotein may be analogous to analbuminemia, a benign genetic trait.

PMID- 1379777
TI  - The effect of gestational age on maternal serum alpha-fetoprotein levels in
      pregnancies with Down syndrome.

PMID- 1379778
TI  - "Doing battle": a metaphorical analysis of diabetes mellitus among Navajo people.
AB  - Effective communication with patients and their family members forms the
      foundation of a therapeutic relationship. This is particularly important when the
      occupational therapist, other health professionals, and the patient are from
      different cultural backgrounds. This paper describes one aspect of the findings
      of a ethnographic study of chronic diabetes among the Navajo people (referred to
      here as Dine'). It focuses on the dominant metaphorical images that were used by
      the informants to describe their illness experiences. The data suggest that
      diabetes can be considered a metaphor for larger social changes in the life-style
      and traditions (e.g., away from sheepherding as a means of basic subsistence to
      obtaining urban-centered employment) of native Americans and their effects on the
      Dine'. Implications of our findings include the importance of metaphorical
      communication for perceptions of compliance, powerlessness, and patient and
      therapist satisfaction with the therapeutic relationship.

PMID- 1379779
TI  - Hmong children and their families: consideration of cultural influences in
      assessment.
AB  - Occupational therapists assessing young Hmong children with developmental
      problems must consider their families' cultural beliefs as they affect the design
      of assessment procedures and practices. Choices that families make about health
      and educational services are influenced by their beliefs. Developmental status
      can be affected by unresolved medical problems and the child's general health
      condition. Assessment components based on cultural awareness may improve the
      effectiveness of early identification of Hmong children with developmental delay.
      Appropriate use of interpreters, creation of the most beneficial assessment
      environment, parental report, and observation of functional skills and play
      provide needed information when determining the child's eligibility for early
      intervention services. The author has found that trained interpreters provide the
      most reliable communication between family members and the therapist. Assessments
      in the home environment are encouraged due to the child's age and the need for
      family support and interaction. Parents are an excellent source of information
      about the child's current and past functional abilities. Observations of the
      child's interaction with family members, with objects and toys during play, and
      during functional daily living activities provides the therapist with valuable
      information about the child's need for intervention.

PMID- 1379780
TI  - Immune electron microscopic characterization of monoclonal antibodies to
      Alzheimer neurofibrillary tangles.
AB  - Characterization of eleven monoclonal antibodies (MAbs), raised to isolated
      sodium dodecyl sulfate (SDS)-treated Alzheimer's neurofibrillary tangles (ANT),
      has revealed the presence of at least two different epitopes. MAbs were tested
      for reactivity to ubiquitin and paired helical filaments (PHF) isolated by three
      different procedures. The effect of protease and/or alkaline phosphatase
      pretreatment on the reactivity of the MAbs with isolated PHF was also examined.
      All MAbs that had reacted strongly in the ELISA with sonicated SDS-treated ANT
      also immune decorated isolated PHF to varying degrees. Two MAbs exhibited a high
      reactivity to PHF: 3-39 and 5-25. MAb 3-39 was found to recognize a protease
      sensitive epitope. In contrast MAb 5-25 was found to consistently decorate
      isolated PHF in all preparations and exhibited a strong reactivity to ubiquitin,
      and the epitope in isolated PHF was not protease sensitive. Thus structural PHF
      after protease treatment and detergent treatment contain an antigenic site that
      is present in ubiquitin.

PMID- 1379781
TI  - Expression of tenascin by vascular smooth muscle cells. Alterations in
      hypertensive rats and stimulation by angiotensin II.
AB  - The extracellular matrix glycoprotein tenascin is associated with remodeling
      events in many embryonic and pathologic tissues. The expression of tenascin has
      been investigated by immunohistochemistry in blood vessels of Wistar-Kyoto
      (normotensive) and spontaneously hypertensive rats. Weak tenascin staining was
      present throughout the tunica media of large and small arteries from normotensive
      animals; strong staining was only detectable at branching sites. In arteries from
      hypertensive animals, foci of strong tenascin staining were scattered throughout
      the tunica media. The expression of tenascin mRNA and protein by rat aortic
      smooth muscle cells cultured in serum-free medium was induced by the
      vasoconstrictor peptide angiotensin II. Transforming growth factor-beta and
      platelet-derived growth factor also stimulated tenascin mRNA expression. Vascular
      smooth muscle cells attached specifically to a substratum of tenascin, but
      remained rounded. Thus, increased focal tenascin expression by vascular smooth
      muscle cells is associated with hypertension, and may mediate angiotensin II
      induced changes in vascular structure in hypertension.

PMID- 1379784
TI  - Incorporation of immunostaining data in anatomic pathology reports.

PMID- 1379783
TI  - Keratin expression in cervical cancer.
AB  - Using a panel of 21 monoclonal and 2 polyclonal keratin antibodies, capable of
      detecting separately 11 subtypes of their epithelial intermediate filament
      proteins at the single cell level, we investigated keratin expression in 16
      squamous cell carcinomas, 9 adenocarcinomas, and 3 adenosquamous carcinomas of
      the human uterine cervix. The keratin phenotype of the keratinizing squamous cell
      carcinoma was found to be most complex comprising keratins 4, 5, 6, 8, 13, 14,
      16, 17, 18, 19, and usually keratin 10. The nonkeratinizing variety of the
      squamous cell carcinoma expressed keratins 6, 14, 17, and 19 in all cases,
      usually 4, 5, 7, 8, and 18, and sometimes keratins 10, 13, and 16.
      Adenocarcinomas displayed a less complex keratin expression pattern comprising
      keratins 7, 8, 17, 18, and 19, while keratin 14 was often present and keratins 4,
      5, 10 and 13 were sporadically found in individual cells in a few cases. These
      keratin phenotypes may be useful in differential diagnostic considerations when
      distinguishing between keratinizing and nonkeratinizing carcinomas (using keratin
      10, 13, and 16 antibodies), and also in the distinction between nonkeratinizing
      carcinomas and poorly differentiated adenocarcinomas, which do not express
      keratins 5 and 6. Keratin 17 may also be useful in distinguishing carcinomas of
      the cervix from those of the colon and also from mesotheliomas. Furthermore the
      presence of keratin 17 in a CIN I, II, or III lesion may indicate progressive
      potential while its absence could be indicative of a regressive behavior. Because
      most carcinomas express keratins 8, 14, 17, 18, and 19, we propose that this
      expression pattern reflects the origin of cervical cancer from a common
      progenitor cell, i.e., the endocervical reserve cell that has been shown to
      express keratins 5, 8, 14, 17, 18, and 19.

PMID- 1379782
TI  - Differential expression of proteoglycans on the surface of human melanoma cells
      characterized by altered experimental metastatic potential.
AB  - Heparan sulphate (HS) and chondroitin sulphate (CS) proteoglycans (PGs)
      frequently have opposite biologic functions in cell-matrix adhesion as well as in
      the regulation of cell proliferation. Data revealed that sulphated
      glycosaminoglycans (sGAGs) (sugar chains of PGs) are differently expressed in
      tumor cells characterized by different metastatic potential; the more metastatic
      cells contain a higher HS/CS ratio. As the proliferative capacity of tumor cells
      is also frequently altered in parallel with their metastatic potential, it was
      not clear whether observed PG alterations reflect changes in cell proliferation
      or metastatic potential. The cell-associated PG expression and sGAG biosynthesis
      was studied in tumor cells of human melanoma lines characterized by different
      experimental metastatic potential to the mouse liver but similar in vitro/in vivo
      proliferation rates. Using antibodies against PGs we found different expression
      of PG epitopes in melanoma lines, except from the melanoma antigen. Unlike the
      low CSPG (melCSPG) metastatic melanoma cells, the cell line with high metastatic
      capacity contained a higher proportion of positive cells for surface-HSPG without
      the coexpression of certain cartilage-type CSPG epitopes (recognized by MAb HSFPG
      529) as well as by an increased pericellular HS/CS ratio due to intracellular
      accumulation/retention of CS. Immunocytochemistry of adherent cells revealed
      HSPGs at substrate-attached membrane areas only in cases of highly metastatic
      melanoma cells. These data further support our view that the absolute or relative
      dominance of HSPGs over CSPGs at the cell surface of metastatic tumor cells can
      be considered a marker of a more metastatic phenotype.

PMID- 1379785
TI  - Microwave-assisted PAS stain for frozen sections.

PMID- 1379786
TI  - Antigenic variation among transmissible gastroenteritis virus (TGEV) and porcine
      respiratory coronavirus strains detected with monoclonal antibodies to the S
      protein of TGEV.
AB  - Five nonneutralizing monoclonal antibodies (MAb) generated to the virulent Miller
      strain of transmissible gastroenteritis virus (TGEV) and specific for the S
      protein were characterized. Competition assays between purified and biotinylated
      MAb indicated that MAb 75B10 and 8G11 mapped near a new subsite, designated V and
      2 MAb, 44C11 and 45A8, mapped to a previously designated subsite D. A fifth MAb
      mapped between subsites V and E. These MAb were tested with 3 previously
      characterized MAb to subsites A, E, and F in fixed-cell ELISA and cell culture
      immunofluorescent assays against 5 reference and 9 field strains of TGEV and 2 US
      strains (ISU-1 and ISU-3) of porcine respiratory coronavirus (PRCV). Subsites A,
      E, and F were conserved on all TGEV and PRCV strains examined. The 2 MAb to
      subsite V, 8G11 and 75B10, reacted only with the Miller TGEV strains (M5C, M6,
      and M60), except that 75B10 also recognized field strain U328. The MAb 11H8 did
      not react with 4 field strains or the Purdue strains of TGEV. The 2 MAb to
      subsite D reacted with all TGEV strains examined, but not with 2 US PRCV strains,
      2 European PRCV strains, 1 feline infectious peritonitis virus strain, and 1
      canine coronavirus strain. Because of this specificity for TGEV, but not PRCV,
      these latter 2 subsite D MAb may be useful for the development of competition
      ELISA to differentiate serologically between TGEV and PRCV infections in swine,
      similar to the currently used European subsite D MAb.

PMID- 1379787
TI  - Biochemical study on the process of skin graft take.
AB  - Investigations on the process of skin graft take have been performed by many
      investigators and it has been shown that skin grafts become viable after
      revascularization from the graft bed after passing through a certain period of
      circulatory interruption. However, there are some disagreements between
      researchers regarding the role played by serum and the onset time of
      revascularization. We have investigated the changes in adenosine 5'-triphosphate
      (ATP) and glucose levels of skin grafts in rats to understand the biochemical
      process of skin graft take. A total of 250 male Wistar rats were used, and 450
      microns split-thickness skin grafts were cut from their backs using a dermatome.
      In Group 1, the skin graft was grafted onto the dorsal fascia of the same rat. In
      Group 2, a 191-microns-thick Millipore filter with 1.5-microns pores was
      interposed between the graft and the dorsal fascia to inhibit revascularization.
      In Group 3, the skin graft was enveloped in a piece of gauze containing
      physiological saline solution and incubated at 37 degrees C. Skin grafts were
      removed at 6, 12, and 24 hours as well as on days 2, 3, 4, 5, 6, and 7 after
      grafting. The ATP and glucose levels were extracted from the grafts and
      quantitated using high-performance liquid chromatography. In Group 1, the ATP and
      glucose levels in the graft decreased rapidly after grafting; the ATP level fell
      to approximately 30% of that before grafting and glucose to about 20%, on days 2
      and 3, respectively. Thereafter, these levels increased gradually.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1379788
TI  - Polymerase chain reaction strategy.

PMID- 1379789
TI  - Estradiol regulates class I alcohol dehydrogenase gene expression in renal
      medulla of male rats by a post-transcriptional mechanism.
AB  - Rat kidney contains alcohol dehydrogenase (ADH) activity which appears to be
      identical to the class I ADH expressed in liver. Treatment of male rats with
      estradiol for 10 days induced ADH activity and protein in the kidney
      approximately 3-fold. This was not the result of suppression of testosterone
      levels by estrogen, as castration did not increase ADH activity. In situ
      hybridization of kidney sections showed that ADH transcripts were localized to
      the medulla, that the basal level of mRNA is very low in the male, and that the
      induction of ADH mRNA by estradiol was approximately 10-fold. As estimated from
      Northern blot analysis, the induction of the mRNA was approximately 7-fold. Thus,
      induction of ADH mRNA substantially exceeded the increase of ADH activity and
      protein. Since the estradiol-treated rats lost weight relative to the oil
      injected controls, the effect of starvation on ADH mRNA in kidney was examined.
      Starvation decreased kidney ADH activity by about 30% but increased mRNA about 2
      fold. Time course experiments demonstrated induction of ADH mRNA by estradiol
      within 1 h with the maximum level achieved by 24 h. The transcription rate of the
      ADH gene as assessed by nuclear run-on assays performed at 1 and 24 h after
      treatment with estradiol was unchanged. We conclude that estradiol induces ADH
      mRNA in kidney by a post-transcriptional mechanism.

PMID- 1379790
TI  - Two coding regions closely linked to the rat apolipoprotein E gene: nucleotide
      sequences of rat apolipoprotein C-I and ECL cDNA.
AB  - Restriction fragments isolated from a 17-kb rat genomic DNA clone containing the
      gene for apolipoprotein (apo) E were radiolabeled and used to screen a rat liver
      cDNA library. A cDNA clone hybridizing to a 6-kb genomic DNA fragment was
      isolated and the nucleotide sequence of the cDNA insert determined. The sequence
      was homologous to the sequence for human apo C-I and was used to derive the
      corresponding amino acid sequence. Unlike human apo C-I, mature rat apo C-I
      contains histidine, lacks valine, and has alanine at the C terminus and aspartate
      as the N terminus. Screening the rat liver cDNA library with a radiolabeled 1.9
      kb restriction fragment from the genomic DNA clone containing the rat apo E gene
      identified another cDNA clone (ECL cDNA). Nucleotide sequencing yielded a derived
      75-amino-acid sequence for the ECL protein with a hydrophobicity profile similar
      to that of rat apo C-I. Northern analysis demonstrated a 0.50-kb band for ECL
      mRNA. The tissue-specific expression of the gene is similar to that of rat apo C
      I. This study indicates that the rat apo C-I and ECL genes are closely linked,
      about 4.5 and 12 kb downstream of the apo E gene, respectively.

PMID- 1379791
TI  - Phosphatidic acid and lysophosphatidic acid stimulate receptor-regulated membrane
      currents in the Xenopus laevis oocyte.
AB  - External application of dioleoyl-phosphatidic acid and oleoyl-lysophosphatidic
      acid stimulated Ca(2+)-dependent chloride currents in voltage-clamped Xenopus
      laevis oocytes. The responses were observed in oocytes from which follicular
      cells had been removed, indicating they were intrinsic to the oocyte itself. The
      lipid-induced Ca(2+)-dependent chloride currents were observed in the absence of
      extracellular calcium, were blocked by intracellular injection of the calcium
      chelator, bis(O-aminophenoxy)-ethane N,N,N'N'-tetraacetic acid, and could not be
      elicited by direct intracellular injection of the active lipids. The thresholds
      for dose-dependent current responses to dioleoyl-phosphatidic acid (100 nM) and
      for oleoyl-lysophosphatidic acid (10 nM) indicated that the lipid activities on
      oocytes were potent. With repeated or prolonged administration of either active
      lipid, responses exhibited desensitization. These results demonstrate that the
      Xenopus oocyte expresses endogenous functional responses for the mitogenic lipids
      phosphatidic acid and lysophosphatidic acid and thus provides a powerful model
      for characterization of the pharmacology and transduction pathways of these
      responses.

PMID- 1379792
TI  - A bullous skin disease patient with autoantibodies against separate epitopes in 1
      mol/L sodium chloride split skin.
AB  - BACKGROUND: We describe a patient with a subepidermal bullous skin disease
      associated with autoantibodies recognizing separate epitopes in 1 mol/L sodium
      chloride (NaCl) split skin. OBSERVATIONS: Direct immunofluorescence microscopy
      showed deposits of immunoglobulins and C3 in a continuous pattern in the
      patient's epidermal basement membrane zone. Direct immunoelectron microscopy
      demonstrated thick deposits of IgG overlying the lamina lucida and the lamina
      densa in a unique pattern. The patient had circulating IgG anti-basement membrane
      zone antibodies that bound both sides of 1 mol/L NaCl split skin, exhibited at
      least a fourfold-higher titer against the dermal side of this test substrate, and
      bound basal keratinocyte hemidesmosomes as well as focal sites along the superior
      portion of the lamina densa on indirect immunoelectron microscopy. Affinity
      purification of anti-basement membrane zone antibodies against epidermal or
      dermal strips of 1 mol/L NaCl split skin yielded IgG that only bound the side of
      split skin from which it was eluted. The patient's serum contained IgG that
      immunoprecipitated and immunoblotted the 230- and 170-kd bullous pemphigoid
      antigens. Affinity purification of patient antibody against bullous pemphigoid
      antigen immobilized on nitrocellulose paper yielded IgG that bound only the
      epidermal side of 1 mol/L NaCl split skin. The patient showed no evidence of
      reactivity against type VII collagen by direct immunoelectron microscopy,
      indirect immunoelectron microscopy, or immunoblot. CONCLUSIONS: This patient's
      bullous skin disease is associated with IgG anti-basement membrane zone
      antibodies with two specificities: one recognizing the bullous pemphigoid antigen
      in the epidermal side of 1 mol/L NaCl split skin, and another binding a distinct,
      yet presently unidentified, epitope in the superior aspect of the lamina densa.

PMID- 1379793
TI  - Metastatic nasopharyngeal carcinoma initially presenting as cervical
      lymphadenopathy. A report of two cases that resembled Hodgkin's disease.
AB  - We describe two patients with nasopharyngeal carcinoma who initially presented
      with cervical lymphadenopathy. Lymph node biopsy specimens in each patient were
      initially diagnosed as Hodgkin's disease. In both cases, the neoplastic cells had
      large, vesicular nuclei with prominent eosinophilic nucleoli; some neoplastic
      cells were identified in lacunar spaces. In addition, numerous inflammatory cells
      were present, including eosinophils, lymphocytes, and plasma cells. At the time
      of referral, the correct diagnosis of metastatic carcinoma was made, and primary
      nasopharyngeal carcinomas were subsequently identified. The possibility of
      metastatic nasopharyngeal carcinoma should always be considered in adults with
      enlarged cervical lymph nodes that resemble Hodgkin's disease. The cytologic
      features of the malignant cells are the clue to the correct diagnosis.
      Immunophenotypic studies easily resolve this diagnostic dilemma if the
      possibility of metastatic nasopharyngeal carcinoma is considered.

PMID- 1379794
TI  - Cardiovascular cyclic nucleotide phosphodiesterases and their role in regulating
      cardiovascular function.
AB  - We have described five phosphodiesterase (PDE) isozymes that can be found in
      cardiac and vascular smooth muscle of animals and humans. Much of the evidence
      for the role that these isozymes have in the regulation of cellular processes has
      been generated through, or awaits, the identification of selective and potent PDE
      inhibitors. While selective inhibitors of the cGMP-inhibitable (cGi)-PDE isozyme
      have been approved for use in the acute treatment of heart failure, selective
      inhibitors of the cGMP-PDE have not been extensively explored as potential
      candidates for the treatment of cardiovascular diseases. More potent selective
      inhibitors of the cGMP-PDE isozyme are needed to determine whether these
      pharmacological potentiators of EDRF and ANP will be useful in the therapy of
      angina, hypertension or heart failure.

PMID- 1379795
TI  - [The effect of a restriction of the feed intake on the composition of the blood
      and on the development and composition of different tissues of sheep during
      growth. 2. The development of different tissues and the concentration of protein,
      DNA and RNA].
AB  - The concentration of protein in the cerebrum of sheep after a period of feed
      restriction (group 2) was lower (94.5 +/- 10.2) than in normally fed sheep of
      group 4 (101.4 +/- 9.4 mg/g wet weight). In the group 2 the concentration of
      protein in the M. longissimus dorsi and in the M. semimembranosus was also
      smaller. A high DNA-concentration was determined in the intestinal lymph nodes,
      in the spleen and in the lung. The DNA-concentration of the testes of group 2
      (7.17 +/- 2.92) was higher than that of the group 4 (4.46 +/- 1.70 mg/g w. w.),
      also that of the renal fat tissue (0.39 +/- 0.18 resp. 0.20 +/- 0.09). The
      highest protein: DNA-relation in group 4 was found in the fat tissue (203.5: 1)
      and the lowest in the spleen (15.3: 1). A high RNA-concentration was analysed in
      the lymph nodes, in the spleen and in the lung. The RNA-concentration in the fat
      tissue of group 2 (0.34 +/- 0.13) was higher that that in group 4 (0.15 +/- 0.08
      mg/g w. w.).

PMID- 1379796
TI  - Interferons induce xanthine dehydrogenase gene expression in L929 cells.
AB  - Human interferon-alpha A/D (Bg/II) (IFN-alpha A/D) and mouse interferon-gamma
      (IFN-gamma) are shown to induce xanthine dehydrogenase (XD) mRNA in L929
      fibroblastic cells. XD mRNA accumulation after IFN-alpha A/D treatment is
      relatively fast, being already evident after 4 h and reaching its maximum after
      24 h. IFN-alpha A/D is active in inducing XD mRNA at 0.1 unit/ml and it is
      maximally active at 10(3) units/ml. The half-life of the XD message is unaffected
      by IFN-alpha A/D treatment, whereas the transcriptional activity of the XD gene
      and the concentrations of XD heterogeneous nuclear RNA are increased by 2- and 6
      fold respectively. The effect of IFN-alpha A/D on XD mRNA is insensitive to
      cycloheximide, suggesting that protein synthesis de novo is not required.
      Experiments conducted with specific inhibitors suggest that protein kinase C,
      cyclic AMP and arachidonic acid metabolites derived from lipoxygenase or
      cyclooxygenase do not act as second-messenger molecules in the induction of XD
      mRNA by IFN-alpha A/D. XD mRNA is also induced in NIH3T3 fibroblastic cells, but
      not in F9 teratocarcinoma or B16 melanoma cells after treatment with IFN-alpha
      A/D. NIH3T3 are the only cells so far tested that have detectable XD and xanthine
      oxidase activities under basal conditions and after IFN-alpha A/D treatment,
      although their responsiveness to the cytokine is much less than that observed in
      L929 cells.

PMID- 1379797
TI  - Renaturation and partial peptide sequencing of mitogen-activated protein kinase
      (MAP kinase) activator from rabbit skeletal muscle.
AB  - Mitogen-activated protein kinase (MAP kinase) activator was purified 2000-fold
      from skeletal muscle, and proteins which co-purified with the activator were
      analysed after SDS/PAGE by renaturation and partial sequencing. Activity for
      tyrosine and threonine phosphorylation of MAP kinase was present in two bands of
      approx. 48 and 46 kDa, which have sequence similarity to small GTP-binding
      protein p25 GDP dissociation inhibitor and protein kinases (PBS2, SPK1+, STE7,
      BYR1) respectively.

PMID- 1379798
TI  - Changes in keratin expression during fetal and postnatal development of
      intestinal epithelial cells.
AB  - We have investigated keratin expression in fetal, newborn and adult rat
      intestines by immunofluorescence staining, immunoblotting of two-dimensional gels
      and Northern blot analysis of total cellular RNAs. Keratin-type intermediate
      filaments, composed predominantly of keratin no. 19, were observed already in the
      undifferentiated stratified epithelium present at 15-16 days of gestation. The
      marked maturation and differentiation of the epithelium taking place at 18-19
      days of gestation was characterized by the appearance of the differentiation
      specific keratin no. 21 and by a significant increase in the relative amount of
      keratin no. 8. The keratin pattern typical of adult villus cells became
      established at the time of birth, and was marked by a considerable increase in
      the complexity of the keratin-related polypeptides detected on two-dimensional
      gels, indicative of extensive post-translational modification of all keratins.
      Starting at 20 days of gestation there was a major increase in the relative
      abundance of mRNAs coding for keratin nos. 8, 19 and 21; in contrast, the
      relative amount of keratin no. 18 mRNA reached a peak shortly after birth and
      declined to very low levels in adult intestine. These results demonstrated marked
      changes in keratin expression and post-translational processing taking place at
      key stages of intestinal development. The appearance of keratin no. 21 in
      coincidence with the formation of an adult-type brush border and terminal web
      would be consistent with it having an important role in the organization of the
      intermediate filament network in the apical cytoplasm of the differentiated
      intestinal cells.

PMID- 1379799
TI  - The rat angiotensin II AT1A receptor couples with three different signal
      transduction pathways.
AB  - To examine whether the subpopulation of the rat type 1 angiotensin II (AII)
      receptor (AT1A) couples with a single or multiple signal transduction pathways,
      we constructed Chinese hamster ovary (CHO) cell lines producing the recombinant
      receptor. The expressed AT1A receptor exhibits typical pharmacological
      characteristics of the AT1 receptor, known to mediate the main physiological
      function of AII. Addition of AII to the CHO cells induced a rapid, transient
      increase in intracellular free Ca2+ concentrations ([Ca2+]i) followed by a lower,
      sustained phase. Nicardipine, a blocker of voltage-dependent L-type Ca2+
      channels, attenuated the transient [Ca2+]i response and abolished the sustained
      phase. The transient phase was also reduced dose-dependently by the phospholipase
      C inhibitor neomycin. Furthermore, AII inhibited forskolin-evoked cAMP
      accumulation. These data suggest, although another subpopulation named AT1B is
      present, that the rat AT1A receptor can independently couple with all three
      signal transduction pathways known to be induced by AII: i.e., i) activation of
      phospholipase C resulting in InsP3 generation with a subsequent release of
      intracellularly stored Ca2+, ii) activation of dihydropyridine-sensitive voltage
      dependent Ca2+ channels, and iii) inhibition of adenylate cyclase activity.

PMID- 1379801
TI  - Hammerhead ribozyme cleavage of hamster prion pre-mRNA in complex cell-free model
      systems.
AB  - The cleavage properties of a trans-acting hammerhead ribozyme targeted 51 bases
      upstream of the putative splicing branch point in the hamster prion pre-mRNA
      intron were investigated in cell-free model systems in vitro. The specificity of
      cleavage was demonstrated by the inability of this ribozyme to cleave a non
      homologous synthetic message encoding part of the beta amyloid peptide precursor,
      beta APP, and by the inability of the prion pre-mRNA to be cleaved by a ribozyme
      targeted to beta amyloid peptide precursor mRNA. Also, the addition of total RNA
      isolated from rat brain had only a minimal effect on the cleavage of the prion
      substrate pre-mRNA by the ribozyme. Finally neither the presence of 100 ng of
      nuclear or cytoplasmic proteins were found to affect the rate of cleavage in
      vitro.

PMID- 1379800
TI  - A plasminogen-related gene is expressed in cancer cells.
AB  - The breakdown of blood clots requires the fibrinolytic action of the serine
      proteinase plasmin, a two-chain polypeptide derived posttranslationally from its
      precursor zymogen, plasminogen. While investigating plasminogen gene expression
      in human extrahepatic tissues, a cDNA sequence was obtained which closely
      resembled the plasminogen cDNA, yet appeared to represent a distinct gene
      product. This sequence, which represents the transcript of the recently
      characterized plasminogen-related gene B, encodes a putative polypeptide of Mr
      8800 and is expressed most prominently in malignant cancer cells.

PMID- 1379802
TI  - Leukocyte chemotactic activity of FKBP and inhibition by FK506.
AB  - Cyclophilin, the cyclosporin A binding protein and member of the immunophilin
      family of proteins, demonstrates leukocyte chemotactic activity. In this study we
      demonstrate that FKBP, the FK506 and rapamycin binding protein, also displays
      leukocyte chemotactic activity. The chemotactic activity of FKBP is inhibited by
      FK506, however, FK506 was unable to inhibit cyclophilin-stimulated chemotactic
      activity. Rapamycin was unable to prevent the chemotactic activity of FKBP,
      similarly, the CsA analogue Me6Ala-CsA while displaying cyclophilin binding was
      unable to block cyclophilin-stimulated chemotactic activity. These results
      suggest that in addition to their intracellular role the immunophilins may also
      function as chemotactic agents, furthermore this activity is modulated by
      immunosuppressants.

PMID- 1379803
TI  - Porin of Pseudomonas aeruginosa forms low conductance ion channel in planar lipid
      bilayers.
AB  - Protein E1, a porin of the outer membrane of Pseudomonas aeruginosa, was
      reconstituted into planar lipid bilayers. Single channel conductance of the
      protein appeared to be 230 pS (pico siemens) in 1 M KCl-10 mM Hepes, pH7.2. This
      value is approximately 5 times lower than the conductance of the OmpF channel of
      Escherichia coli. Conductance increased linearly as the membrane potential was
      raised from -200 mV to +200 mV, and was nearly proportional to the KCl
      concentration. These results show that protein E1 is probably a genuine porin in
      the P. aeruginosa outer membrane supporting the earlier conclusion that protein
      E1 forms a small channel.

PMID- 1379804
TI  - Interleukin-8 inhibits the induction of nitric oxide synthase in rat peritoneal
      neutrophils.
AB  - The effect of interleukin(IL)-8 and leukotriene B4 (LTB4) on the induction of
      nitric oxide (NO) synthase in rat peritoneal neutrophils (PMN) ex vivo was
      studied. IL-8, but not LTB4, caused concentration-dependent inhibition of the
      induction of a Ca(2+)-independent NO synthase ex vivo. The effect of IL-8 was not
      attributable to the synthesis of an inhibitor of this enzyme. These findings
      suggest complex regulatory control of the induction of NO synthase by cytokines.

PMID- 1379805
TI  - Species heterogeneity of hepatic alpha 1-adrenoceptors: alpha 1A-, alpha 1B- and
      alpha 1C-subtypes.
AB  - alpha 1-Adrenergic activation stimulated phosphorylase and phosphoinositide
      turnover in hepatocytes from guinea pigs, rats and rabbits. Chlorethylclonidine
      inhibited these effects in rat and rabbit cells but not in guinea pig
      hepatocytes; low concentrations of 5-methyl urapidil blocked the alpha 1 actions
      in guinea pig and rabbit liver cells, but not in rat hepatocytes. Binding
      competition experiments also showed high affinity for 5-methyl urapidil in liver
      membranes from guinea pigs and rabbits and low affinity in those from rats. The
      data indicated that guinea pig hepatocytes express alpha 1A-, rat hepatocytes
      alpha 1B- and rabbit hepatocytes alpha 1C- adrenoceptors. This was confirmed by
      Northern analysis using receptor subtype-selective probes.

PMID- 1379806
TI  - Inhibition of class II MHC gene expression by anti-sense RNA in transgenic mice.
AB  - We have established transgenic mice carrying the anti-sense DNA to the gene
      encoding beta chain of the class II major histocompatibility complex (I-A)
      molecule. The amount of I-A molecule on splenic B lymphocytes from the mice was
      reduced in the presence of a large amount of the exogenous anti-sense RNA. The
      amount of I-A beta chain RNA was selectively reduced and inversely correlated
      with the amount of anti-sense RNA in the spleens. These results suggest that the
      I-A beta chain RNA is rapidly degraded by duplex formation with the anti-sense
      RNA in splenic B cells from the transgenic mice.

PMID- 1379807
TI  - Evidence for elevation of cytochrome P4502E1 (alcohol-inducible form) mRNA levels
      in rat kidney following pyridine administration.
AB  - The effects of pyridine on renal cytochrome P4502E1 (CYP2E1) expression in rat
      have been examined by immunoblot and Northern blot analyses. Immunoblot analyses
      revealed that 2E1 protein levels were elevated from 1.4- to 4.6-fold following
      pyridine administration in a dose- and time-dependent manner. Northern blot
      analyses revealed that renal 2E1 poly(A)+ RNA levels increased from 1.4- to 3.8
      fold following pyridine treatment and that these increases in 2E1 mRNA paralleled
      the dose- and time-dependent increases in 2E1 protein content. In contrast,
      hepatic 2E1 poly(A)+ RNA levels failed to increase following these same dosing
      regimens, suggesting that metabolic alterations, such as those associated with
      starvation, were not etiologic factors in renal 2E1 induction. These results show
      that pyridine induced CYP2E1 in kidney and that elevation of renal 2E1 protein
      levels accompanying pyridine administration occurred at least partly as a
      consequence of increased 2E1 poly(A)+ RNA levels. The results of this research
      reveal that regulatory mechanisms governing CYP2E1 expression may differ in
      hepatic and renal tissues.

PMID- 1379808
TI  - Lipopolysaccharide and cytokines induce a macrophage-type of nitric oxide
      synthase in bovine retinal pigmented epithelial cells.
AB  - The present study demonstrates that bovine retinal pigmented epithelial cells,
      which are neuroectodermal in origin, produce nitric oxide (NO) upon treatment
      with interferon-gamma in the presence of lipopolysaccharide or tumor necrosis
      factor-alpha. NO production was measured by the accumulation of the stable
      endproduct NO2-. The biosynthesis of NO requires an induction period of
      approximately 12 hours and continues for at least 96 hours. The synthesis was
      abolished by the stereoselective inhibitors of NO synthase, NG-monomethyl-L
      arginine and NG-nitro-L-arginine-benzylester. Cycloheximide and dexamethasone
      blocked cytokine-induced NO production. The results indicate that endotoxin and
      cytokines are capable of inducing NO synthase of the macrophage type, in retinal
      pigmented epithelial cells.

PMID- 1379809
TI  - Identification of osteopontin in isolated rabbit osteoclasts.
AB  - Bone remodeling is a complex process coupling bone formation and resorption.
      Osteoblasts, the bone-forming cells, are known to produce various bone matrix
      proteins and cytokines; however, little is known about protein factors produced
      by osteoclasts or bone-resorbing cells. A method utilizing the high affinity of
      osteoclasts for tissue culture dishes was developed to isolate a large number of
      pure osteoclasts from rabbit long bones. A cDNA library was then constructed from
      these isolated osteoclasts, and differential cDNA screening was performed between
      osteoclasts and spleen cells. Two clones representing osteoclast-specific clones,
      named OC-1 and OC-2, were isolated. By Northern blot analysis, OC-1 was expressed
      in osteoclasts and in kidneys, whereas OC-2 was specific for osteoclasts. OC-1
      was found to encode osteopontin from its nucleotide sequence, and therefore,
      osteopontin may have other functions for osteoclastic bone resorption besides
      osteoclast attachment to bone.

PMID- 1379810
TI  - Rat copper/zinc superoxide dismutase gene: isolation, characterization, and
      species comparison.
AB  - A 13 kb rat Cu/ZnSOD genomic clone has been purified from a rat liver genomic
      library and completely characterized by restriction mapping, detailed sequencing
      and Southern blot analysis. This gene spans approximately 6 kb and contains five
      exons and four introns. Comparison of rat, mouse, and human Cu/ZnSOD genes
      reveals a high conservation in genomic organization and exon-intron junctions,
      including an unusual 5'GC donor sequence at the first intron. The gene contains a
      TATA box as well as an inverted CCAAT box, a feature common to both the mouse and
      human genes. Furthermore, several repeats were identified in the 5' promoter
      region of this gene, and these regulatory elements are also strikingly conserved
      in these three species.

PMID- 1379811
TI  - Marked induction of hepatocyte growth factor mRNA in intact kidney and spleen in
      response to injury of distant organs.
AB  - Hepatocyte growth factor (HGF) is a potent mitogen for various epithelial cells,
      including mature hepatocytes and renal tubular cells. Here, HGF mRNA was found to
      be markedly increased in non-injured kidney and spleen, when the liver or kidney
      in rats was injured by 70% partial hepatectomy or unilateral nephrectomy. HGF
      mRNA increased to 3-4 fold higher level than the normal in the kidney and spleen
      as well as in the remnant liver after partial hepatectomy. Similarly, HGF mRNA
      markedly increased in the spleen as well as in the remnant kidney after
      unilateral nephrectomy. These results suggest that the onset of injury to the
      liver or kidney may be recognized by distal non-injured organs by the signalling
      of a humoral factor and that HGF derived from these organs may be involved in the
      regeneration of liver or kidney, through an endocrine mechanism.

PMID- 1379813
TI  - [The rebirth of the H1-antagonists].
AB  - Anti H1s of the third generation, of which the first was Terfenadine, possess not
      only blocking effects on H1 receptors to histamine, but also have a "cromone
      like" action on the membranes of cells that have been, or not, activated by
      specific stimuli (antigens). They act on the early phase of immediate
      hypersensitivity. These anti H1s of the new generation also have wider
      indications: asthma, perennial or pollen rhinitis, dermatoses such as urticaria
      and atopic dermatitis. Their tolerance has been remarkably improved with regard
      to the central effect (very reduced), such as absence of an atropine effect.

PMID- 1379812
TI  - Effect of repeated oral doses of a novel immunosuppressive macrolide lactone on
      hepatic mixed-function oxidase system in the rat. Comparative study with
      ciclosporin.
AB  - Effect of pretreatment of rats with FK506((-)
      (1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-allyl-1,14- dihydroxy-12-[(E)
      2-[(1R,3R,4R)-4-hydroxy-3methoxycyclohexyl]-1- methylvinyl]-23,25-dimethoxy
      13,19,21,27-tetramethyl-11,28-dioxa-4- azatricyclo-[22.3.1.0(4.9)]octacos-18-ene
      2,3,10,16-tetrone hydrate, CAS 104987-11-3) on microsomal cytochrome P-450 system
      and oxidations of the administered drug and other model substrates were studied
      and compared with those of a pharmacologically related drug, ciclosporin
      (cyclosporin A). Oral treatment of male Sprague-Dawley rats with FK506 (0.4, 2 or
      10 mg/kg/d) for 7 days did not decrease microsomal content of total cytochrome P
      450 in livers, but rather increased the content in groups with the dose of 0.4 or
      10 mg/kg to the levels of 126-130% of the control. Microsomal NADPH-cytochrome c
      reductase activities were decreased up to 67% of the control with the increasing
      dose of FK506 and to 62% in a group treated orally with cyclosporin A (25 mg/kg/d
      for 7 days), although another microsomal electron-transport component, cytochrome
      b5, was rather increased in all the treated groups. Treatment with FK506 or
      cyclosporin A did not reduce but slightly increased microsomal activities of
      aniline hydroxylation, p-nitroanisole O-demethylation and O-ethoxyresorufin O
      deethylation. Microsomal depropylation of 7-propoxycoumarin, a typical P-450IIIA
      substrate, was also not reduced in all dose groups of FK506, while it was
      decreased by the treatment with 25 mg/kg cyclosporin A.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1379814
TI  - Transcripts encoding protein kinase C-alpha, -delta, -epsilon, -zeta, and -eta
      are expressed in basal and differentiating mouse keratinocytes in vitro and
      exhibit quantitative changes in neoplastic cells.
AB  - The protein kinase C (PKC) family of phospholipid-dependent serine-threonine
      kinases has been implicated in keratinocyte differentiation and neoplastic
      transformation. To determine if Ca(2+)-mediated keratinocyte differentiation is
      associated with changes in PKC isozyme gene expression, RNA was isolated from
      primary mouse keratinocytes grown in medium with 0.05, 0.12, or 1.4 mM Ca2+.
      Based on northern blot analysis, primary keratinocytes expressed mRNA encoding
      PKC-alpha, -delta, -epsilon, -zeta, and -eta, but not PKC-beta or -gamma.
      Relatively little change was detected in the level of these transcripts in cells
      induced to differentiate by exposure to elevated extracellular Ca2+.
      Interestingly, the PKC-zeta transcripts detected in RNA isolated from
      keratinocytes were approximately 200 nucleotides longer than those from mouse
      brain, suggesting the existence of an alternative form of this isozyme. An early
      change in benign neoplastic transformation of keratinocytes is the inability to
      differentiate in response to Ca2+ or the PKC activator 12-O-tetradecanoylphorbol
      13-acetate, which is consistent with altered PKC function in these cells. The PKC
      isozyme mRNA profile was examined in two benign neoplastic keratinocyte cell
      lines, 308 and SP-1, which contain an activating mutation of the c-Ha-ras gene.
      Like normal keratinocytes. 308 and SP-1 cells expressed mRNA encoding PKC-alpha, 
      delta, -epsilon, -zeta, and -eta. However, the abundance of PKC-zeta transcripts
      in both cell lines was reduced by 74-89% when compared with normal keratinocytes
      at similar Ca2+ levels. In addition, SP-1 but not 308 cells exhibited a sevenfold
      increase in PKC-eta mRNA when cultured in medium with 1.4 mM Ca2+. To address
      whether these changes were related to the presence of an activated ras gene, RNA
      was isolated from primary keratinocytes transduced to a benign neoplastic
      phenotype with the v-Ha-ras oncogene. As with normal, 308, and SP-1 cells, v-Ha
      ras keratinocytes expressed mRNA encoding PKC-alpha, -delta, -epsilon, -zeta and 
      eta. The level of PKC-zeta transcripts was similar in normal and v-Ha-ras
      keratinocytes, indicating that reduction of this mRNA in both 308 and SP-1 cells
      was not a direct result of ras activation. As in SP-1 cells, PKC-eta in v-Ha-ras
      keratinocytes was responsive to extracellular Ca2+, with a four-fold increase in
      transcript abundance in 0.12 mM Ca2+ medium relative to 0.05 mM Ca2+
      medium.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1379815
TI  - Alterations in tumor angiogenesis associated with stable expression of the HIV
      tat gene.
AB  - Recent evidence suggests that the human immunodeficiency virus type 1 (HIV) trans
      activator gene (tat) has transforming properties and may be a causative factor in
      the development of certain types of cancers, in particular Kaposi's sarcoma
      (i.e., Vogel J. et al. Nature 335:606-611, 1988). To help elucidate the potential
      role or roles of the HIV tat gene in neoplastic transformation, cell lines were
      constructed that constitutively express a functional tat gene product. HeLa cells
      were coelectroporated with two plasmids, one containing the HIV tat gene in an
      expression cassette and another containing the dominant selectable marker gene
      xanthine guanine phosphoribosyltransferase (XGPRT). After XGPRT selection, single
      cell clones that expressed a functional tat protein were identified by measuring
      chloramphenicol acetyltransferase (CAT) activity after electroporating a plasmid
      containing the CAT gene transcriptionally controlled by HIV trans-activation
      responsive region (tar). Phenotypic alterations resulting from the expression of
      tat were then determined. Control cells and tat-expressing cells grew at similar
      rates in culture. However, when grown as tumors in nude mice, tat-expressing
      cells produced a lower percentage of tumors, and the tumors that were produced
      either regressed, stopped growing, or grew at a very reduced rate compared with
      cells not expressing tat. These differences may have resulted from a tat
      associated reduction in neovascularization in the tumors. A comparison of total
      cellular proteins by two-dimensional polyacrylamide gel electrophoresis indicated
      only one reproducible alteration in a polypeptide of approximately 44 kDa and pl
      of approximately 6.2 associated with tat expression. These cells may be very
      useful in future in vitro and in vivo studies designed to examine the effects of
      HIV tat on endothelial and vascular smooth-muscle cells and the role of tat in
      the etiology of Kaposi's sarcoma.

PMID- 1379817
TI  - Differential induction of 12-O-tetradecanoylphorbol-13-acetate sequence gene
      expression in murine melanocytes and melanoma cells.
AB  - We previously showed that growth of the nontumorigenic, immortal murine
      melanocyte line Mel-ab correlates with the depletion of protein kinase C (PKC),
      whereas quiescence is associated with elevated levels of this enzyme (Brooks G,
      et al., Cancer Res 51: 3281-3288, 1991). Here we report responses that occur in
      these cells downstream of PKC activation or downregulation. We examined induction
      of 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible sequence (TIS) gene
      expression in Mel-ab melanocytes and in their transformed counterparts, B16
      melanoma cells. Exposure of quiescent Mel-ab cells to the PKC-activating phorbol
      esters TPA or sapintoxin A at 81 nM for 2 h increased levels of mRNA for six of
      seven TIS genes examined (twofold to 80-fold increase in steady-state RNA levels
      for TIS 1, 7, 8, 11, 21, and 28 (c-fos); TIS 10 expression was not affected). No
      induction of TIS gene expression was observed either in growing Mel-ab cells
      maintained in 324 nM phorbol 12,13-dibutyrate or in B16 cells previously
      unexposed to phorbol esters, in which normal PKC levels were endogenously
      depressed. The cAMP-elevating agents choleratoxin (10 nM) and dibutyryl cyclic
      AMP (2.5 mM) increased levels of TIS mRNA (with the exception of TIS 10) in both
      proliferating Mel-ab and B16 cells, suggesting that downregulation of the PKC
      pathway is specific and not a consequence of a general inhibition of all
      signalling pathways.

PMID- 1379816
TI  - Homologous and heterologous gap-junctional intercellular communication in v-raf-,
      v-myc-, and v-raf/v-myc-transduced rat liver epithelial cell lines.
AB  - We examined gap-junctional intercellular communication (GJIC) in a series of
      normal and v-raf-, v-myc-, and v-raf/v-myc-transduced rat liver epithelial (RLE)
      cell lines using the scrape loading-dye transfer and fluorescence-recovery-after
      photobleaching (FRAP) assays. Whereas the normal RLE cell line, the control
      helper virus-transduced cell line, and the v-myc-transduced cell line all showed
      excellent GJIC, the v-raf-transduced cell lines displayed decreasing levels of
      GJIC associated with their increasing tumorigenicity. The v-raf/v-myc-transformed
      cell lines showed the lowest levels of GJIC and were also the most tumorigenic.
      Heterologous GJIC of these oncogene-transduced cell lines was also compared with
      that in the normal RLE cells. A modified FRAP assay, using fluorescent-microbead
      labelling to identify the oncogene-transduced cell from surrounding normal cells,
      was used to quantify the heterologous GJIC. The v-raf/v-myc-transformed RLE cells
      had no heterologous communication with the normal RLE cells, whereas v-raf- and v
      myc-transduced cell lines maintained heterologous GJIC. Northern analysis showed
      that connexin 43 was the only gap-junction protein message expressed in these
      cell lines; connexin 32 and connexin 26 were not expressed. The levels of
      connexin 43 mRNA expression were relatively unchanged in all cell lines,
      suggesting that the reduction in GJIC was primarily at the posttranslational
      level. These findings suggest that reduction of homologous GJIC in v-raf- and v
      raf/v-myc-transformed RLE cells is linked to their tumorigenic potential.
      Furthermore, the loss of heterologous GJIC, which we observed only in the v-raf/v
      myc-transformed cells, might release such cells from the growth-regulating
      effects of surrounding normal cells, possibly contributing to their enhanced
      tumorigenic potential.

PMID- 1379818
TI  - Myelodysplastic syndromes. Pathogenesis, diagnosis and treatment.
AB  - Our understanding of the biology of leukemia and myelodysplasia is still only
      partial. The diagnosis of myelodysplasia is often based on quantitative and
      qualitative findings in the peripheral blood and bone marrow. These findings are
      often shared by other disorders. There is a need for sensitive and inexpensive
      laboratory tests to determine clonality and karyotypic abnormalities in this
      disorder. Future classifications of these syndromes will need to be based on
      morphologic and biologic markers that are closely linked to disease progression,
      response to treatment, and survival. Our limited understanding of the
      pathogenesis of MDS decreases the specificity and effectiveness of our
      therapeutic interventions. Agents that are minimally toxic such as CRA, danazol,
      1,25-dihydroxyvitamin D3, androgens, and pyridoxine are seldom useful.
      Antileukemic therapy and allogeneic bone marrow transplantation have a major role
      to play in patients younger than 45 years of age; in older patients these
      treatment modalities remain controversial because of their toxicity.
      Hematopoietic growth factors, used alone or in combination, may improve the
      quality of life and improve survival of patients with MDS. Growth factors may
      also decrease treatment-related mortality associated with chemotherapy and bone
      marrow transplantation and render these treatment modalities available for a
      higher percentage of patients. The development of more specific differentiating
      agents may permit hematopoietic differentiation while minimizing side effects.

PMID- 1379819
TI  - Inspired respiratory solutions.

PMID- 1379820
TI  - Interaction of charybdotoxin with permeant ions inside the pore of a K+ channel.
AB  - Charybdotoxin (CTX) blocks high conductance Ca(2+)-activated K+ channels by
      binding to a receptor site in the externally facing "mouth." Toxin bound to the
      channel can be destabilized from its site by K+ entering the channel from the
      opposite, internal, solution. By analyzing point mutants of CTX expressed in E.
      coli, assayed with single Ca(2+)-activated K+ channels reconstituted into planar
      lipid bilayers, we show that a single positively charged residue of the peptide,
      Lys-27, wholly mediates this interaction of K+ with CTX. If position 27 carries a
      positively charged residue, internal K+ accelerates the dissociation rate of CTX
      in a voltage-dependent manner; however, if a neutral Asn or Gln is substituted at
      this position, the dissociation rate is completely insensitive to either internal
      K+ or applied voltage. Position 27 is unique in this respect; charge-neutral
      substitutions made at other positions fail to eliminate the K+ destabilization
      phenomenon. The results argue that CTX bound to the channel positions Lys-27
      physically close to a K(+)-specific binding site on the external end of the
      conduction pathway and that a K+ ion occupying this site destabilizes CTX via
      direct electrostatic repulsion with the epsilon-amino group of Lys-27.

PMID- 1379821
TI  - Plasticin, a novel type III neurofilament protein from goldfish retina: increased
      expression during optic nerve regeneration.
AB  - The goldfish visual pathway displays a remarkable capacity for continued
      development and plasticity. The intermediate filament proteins in this pathway
      are unexpected and atypical, suggesting these proteins provide a structure that
      supports growth and plasticity. Using a goldfish retina lambda gt10 library, we
      have isolated a full-length cDNA clone that encodes a novel type III intermediate
      filament protein. The mRNA for this protein is located in retinal ganglion cells,
      and its level dramatically increases during optic nerve regeneration. The protein
      is transported into the optic nerve within the slow phase of axonal transport. We
      have named this protein plasticin because it was isolated from a neuronal pathway
      well known for its plasticity.

PMID- 1379822
TI  - Adhesion molecules on human lung dendritic cells and their role for T-cell
      activation.
AB  - Human lung parenchyma contains potent accessory cells to stimulate T cells with
      many features of dendritic cells (DC), including a strong tendency to form
      aggregates with T cells. As contact phenomena may be crucial for T-cell
      activation, phenotypic and functional studies were conducted on adhesion
      molecules. DC from minced lung were isolated by their loose adherence and by
      their absence of autofluorescent inclusions by flow cytometry. DC compared with
      peripheral blood monocytes (Mo) show an increased density of Class I and II major
      histocompatibility antigens. Unexpectedly, the leukocyte integrins (beta 2 group)
      are decreased in density on DC. CD11a (LFA-1) and CD11b are less expressed,
      whereas CD11c is preserved. In contrast, the beta 1 chains are denser on DC with
      an increase in the alpha 5 chain (CD49e) on their surface. The alpha 4 chain of
      this later group (CD49d) is only weakly present and its ligand VCAM (INCAM-110)
      is not detected. DC-induced allogeneic T-cell proliferation is suppressed by
      antibodies against both the beta 1 and the beta 2 chains with a slight additive
      effect. Among the adhesins, LFA-3 and ICAM-1 are increased on DC compared with
      Mo. Antibodies against LFA-3, and to a lesser extent against ICAM-1, block T-cell
      activation. These data improve our knowledge of the phenotype expressed by DC and
      provide some clues as to how DC adhere with T cells and may transduce signals for
      T-cell activation by cell-cell interactions.

PMID- 1379823
TI  - Immunohistochemical localization of epidermal growth factor and acidic and basic
      fibroblast growth factors in postnatal developing and adult rat lungs.
AB  - Histologic preparations of lungs form 1-, 5-, 10-, 18-, and 25-day-old rats and
      adult rats were probed immunohistochemically with specific antibodies for the
      distribution of epidermal growth factor (EGF), acidic fibroblast growth factor
      (aFGF), and basic fibroblast growth factor (bFGF). Immunoperoxidase staining of
      sections of adult rat lungs with a rabbit polyclonal antibody to bovine EGF was
      strong in ciliated cells of airways and mast cells, nonciliated cells of
      bronchioles, smooth muscle, type II cells of alveoli, and interstitial and
      epithelial cells of alveolar septal regions. Developing postnatal lungs had
      moderate and somewhat diffuse immunoreactivity in all epithelial cells, and more
      intense staining in vascular smooth muscle. Immunoperoxidase staining of adult
      rat lungs with a rabbit polyclonal antibody against bovine aFGF was distributed
      in identical fashion to EGF, with the exception of mast cells which were not
      reactive. These same sights were localized using an immunoperoxidase sequence
      with a rabbit polyclonal antibody to the leu 60-leu 98 fragment of aFGF (aFGFfr)
      with less background. In postnatal developing lungs, immunoreactivity with aFGF
      and aFGFfr preparations was diffuse and moderately intense in epithelial cells
      and vascular smooth muscle. Immunoperoxidase staining of adult rat lung sections
      with a monoclonal antibody to bovine bFGF was strong in hyaluronidase-digested
      preparations. Reactivity was principally confined to alveolar and vascular
      basement membrane regions and external laminae of smooth muscle. In early
      postnatal development, immunoreactivity for bFGF was found in basement membranes
      beneath developing epithelium and the endothelium of vessel wall intima and in
      the adventitia, with reactivity increasing with advancing age.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1379824
TI  - Control of nucleocytoplasmic transport.
AB  - The movement of macromolecules between the nucleus and cytoplasm is tightly
      controlled. In the past few years it has become increasingly apparent that
      nuclear traffic is regulated not only by recognition of specific signals on
      proteins and RNAs, but also by cellular factors that modulate the efficacy with
      which these signals are recognized.

PMID- 1379825
TI  - An immunohistochemical study on neurons and paraneurons of the pre- and post
      natal chicken lung.
AB  - The indirect immunoperoxidase (PAP) method was used on chicken lung specimens
      from embryos ranging in age from 6 days to hatching, chicks and adult chickens of
      up to 6 months. The ontogenesis and distribution of neurons and paraneurons
      containing immunoreactivities for serotonin (5HT), bombesin, vasoactive
      intestinal polypeptide (VIP), substance P (SP) and galanin were investigated.
      Serotonin-immunoreactive paraneurons were first detected in the pulmonary
      mesenchyma of 8-day-old embryos, while in the 12-day-old embryos the following
      neurons and paraneurons were first detected in their respective locations:
      serotonin-immunoreactive paraneurons in the bronchial epithelium; VIP- and
      galanin-immunoreactive ganglionic cells and SP-immunoreactive nerve fibres in the
      intrapulmonary ganglia. At hatching, serotonin-immunoreactive paraneurons in the
      epithelium of the air capillaries and air sacs, and bombesin-immunoreactive
      paraneurons in the epithelium of the primary bronchus, VIP-, galanin- and SP
      immunoreactive nerve fibres in the lamina propria of the primary and secondary
      bronchi and in the pulmonary septa could also be shown. Some serotonin
      immunoreactive small paraneurons were also found in the intrapulmonary ganglia.
      In the adult specimens, VIP-, galanin- and SP-immunoreactive nerve fibre networks
      were observed throughout the primary bronchus wall and in the lung septa. In
      intrapulmonary ganglia, VIP- and galanin-immunoreactive neurons and serotonin
      immunoreactive small paraneurons could be more numerously demonstrated. Moreover,
      bombesin paraneurons occurred in the epithelium of primary and secondary bronchi,
      and serotonin-immunoreactive paraneurons were found in the epithelia of the
      bronchi and air sacs and in some pluricellular bodies in the lamina propria of
      the air sac ostia.

PMID- 1379826
TI  - Expression of the interleukin-2 receptor on human fibroblasts and its biological
      significance.
AB  - In this study, we have investigated the expression of the alpha and beta chains
      of the IL-2 receptor (IL-2R alpha, IL-2R beta) both at the membrane and at
      transcriptional levels during the lifespan of human embryonic fibroblasts. Here
      we show that the mAbs IOT14 and MIK beta 1 directed against the IL-2 binding
      sites of the IL-2R alpha and IL-2R beta respectively, stain human embryonic
      fibroblasts early in their life span. Data from [125I]rIL2 cross-linking
      experiments show the simultaneous expression of two IL-2 binding peptides of 70
      and 55 kDa respectively on embryonic young fibroblasts as on lymphoid activated
      cells. The p55 and the p70 IL-2 binding peptides are shown to be specific for the
      IL-2R alpha and to the IL-2R beta by the finding that these bands are abolished
      by excess amounts of cold IL-2 and mAbs directed against the IL-2 binding sites
      of the alpha and beta chains. Scatchard analysis after [125I]IL-2 labelling shows
      the presence of both high affinity (150 sites with a Kd of 147 pM) and low
      affinity (1100 sites with a Kd of 4 nM) IL-2 binding sites. Northern blot and dot
      blot analysis show the presence of specific transcripts for the IL-2R alpha and
      IL-2R beta genes in early passaged fibroblasts. By contrast, in senescent
      cultures, only the IL-2R beta transcript were detected. Finally, IL-2 at low
      concentrations (36 pM) down modulates the level of the intercellular adhesion
      molecule ICAM-1 in young but not in senescent cultures.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1379827
TI  - High affinity for class II molecules as a necessary but not sufficient
      characteristic of encephalitogenic determinants.
AB  - A direct binding assay specific for IAs molecules has been developed and its
      immunological relevance validated by examining, for a panel of nine different
      synthetic peptides, the correlation between their capacity to bind purified IAs
      and to inhibit IAs-restricted antigen presentation. The IAs assay thus developed
      has then been used to study the IAs binding affinity of a set of overlapping
      peptides spanning the entire myelin basic protein (MBP). It was found that the
      encephalitogenic MBP region corresponds to peptides with high MHC binding
      affinities. Other regions of the MBP that have not been described as being
      pathogenic in the context of IAs molecules have also been found to be high IAs
      binders, suggesting that variables other than MHC affinity are also involved in
      determining the pathogenic potential of self-derived determinants.

PMID- 1379828
TI  - Heart preservation: analysis of cardioprotective infusate characteristics.
      Membrane stabilization, calcium antagonism, and protease inhibition on myocardial
      viability: a biochemical, ultrastructural, functional study.
AB  - Thirty-three canine hearts were isolated after initial cardioplegia and preserved
      for 6 hours in 4 degrees C saline solution with intermittent infusion of
      cardioprotective solution every hour. Reperfusion was observed for 2 hours under
      normothermic cross-circulation. Hearts were divided into five groups depending on
      the agent(s) added to the K(+)-Mg2+ cardioplegic solution (K(+)-Mg(2+)-CP)
      infused. Control hearts (n = 6) received K(+)-Mg(2+)-CP solution alone; group I
      (n = 7) received lidocaine, 200 mg/L, added to the K(+)-Mg(2+)-CP solution; group
      II (n = 7) received betamethasone (250 mg/L) added to the formula for group I;
      group III (n = 6) received diltiazem (200 micrograms/L) added to the formula for
      group II; group IV (n = 7) received aprotinin (150 KIU/L) added to the formula of
      group III. Coronary sinus MB fraction of creatine kinase level was significantly
      decreased at 60 and 120 minutes of reperfusion in group II, as was mitochondrial
      aspartate aminotransferase level at 2 hours of reperfusion. Lysosomal enzyme
      release decreased in group IV. Myocardial adenosine triphosphate levels and total
      adenine nucleotides showed no significant difference among the groups at the end
      of reperfusion; however, myocardial adenosine diphosphate and adenosine
      monophosphate levels during reperfusion increased significantly in group I, and
      myocardial adenosine diphosphate and adenosine monophosphate levels at the end of
      reperfusion in groups I and IV were significantly higher than those of the
      control. Calcium overload, which was lowest in group II, was not completely
      prevented during reperfusion in any group. Left ventricular end-systolic pressure
      volume relationship in group II showed the "best" functional recovery. In
      addition, the ultrastructure of the left ventricular myocardium was well
      preserved in all groups. These results suggest that membrane stabilization with
      lidocaine and betamethasone affords beneficial effects on myocardial biochemical
      and functional viability. Diltiazem appears to be less effective in preventing
      calcium overload during ischemia-reperfusion, and protease inhibition with
      aprotinin (150 KIU/ml) seems to be highly effective in suppressing lysosomal
      enzyme activation-release and maintaining myocardial adenosine diphosphate and
      adenosine monophosphate levels.

PMID- 1379829
TI  - The impact of FK506 on graft coronary disease of rat cardiac allograft--a
      comparison with cyclosporine.
AB  - We studied the impact of FK506, a potent immunosuppressant, on graft coronary
      disease and graft-infiltrating lymphocyte subset after rat heart transplantation.
      Fisher rat heart grafts transplanted into Lewis rat recipients were divided into
      three groups: control (n = 7), rats treated with FK506 at a dose of 0.32
      mg/kg/day intramuscularly (n = 7), and rats treated with cyclosporine at a dose
      of 10 mg/kg/day intramuscularly (n = 7). Grafts were removed on day 71 in the
      treated groups and on rejection in the control group. We blindly scored graft
      rejection and graft coronary disease on a scale of 0 to 4. Graft-infiltrating
      lymphocytes were investigated by flow-cytometric analysis with the following
      monoclonal antibodies: W3/25, anti-helper T lymphocyte; OX8, antisuppressor and
      cytotoxic T lymphocyte; and OX39, antiinterleukin-2 receptor. No difference of
      graft rejection was found between the two treated groups (FK506 1.66 +/- 0.49
      versus cyclosporine 1.45 +/- 0.37), but the FK506 group showed severe graft
      coronary disease (FK506 2.14 +/- 0.82 versus cyclosporine 0.78 +/- 0.17; p less
      than 0.01) in this model. In flow-cytometric analysis, we found an increased
      proportion of OX8-positive lymphocytes (FK506 25.7 +/- 6.4 versus cyclosporine
      4.9 +/- 2.4, p less than 0.01). These results suggest that suppression of
      cytotoxic T lymphocytes may be involved in graft coronary disease.

PMID- 1379830
TI  - Renal cell carcinoma.
AB  - The behavior of renal cell carcinoma remains one of the most unpredictable of the
      genitourinary neoplasms. Once this disease has spread beyond the confines of the
      kidney, it is extremely difficult to control. This year, emphasis has focused on
      the characteristic cytogenetic and chromosomal changes that are seen in this
      tumor that help to explain partially its enigmatic behavior. Immunotherapy
      remains the mainstay of nonsurgical therapy. Recent studies have examined the
      efficacy of using combinations of interferons, interleukin-2, or specific
      subpopulations of lymphoid cells to control metastatic renal cell carcinoma. The
      role of surgery in metastatic disease, tumor extending into the vena cava, and
      parenchyma-sparing operations continues to be examined. This review examines the
      most recent literature on each of these aspects in the treatment of this
      difficult and challenging tumor.

PMID- 1379832
TI  - Metastatic tumors of the axial spine.
AB  - Spinal metastases are the most common tumors of the axial spine. Symptomatic
      spinal metastases in children and adults differ in a number of respects including
      culpable primary tumors, the degree of spinal column involvement, surgical
      strategies, and results of treatment. Magnetic resonance imaging has become the
      imaging method of choice for spinal tumors. The management of symptomatic spinal
      metastases is undertaken to relieve pain and to preserve or restore neurologic
      function. Radiation therapy is generally regarded as the initial treatment of
      choice. However, there has been a steady evolution in concepts and execution of
      surgical strategies for spinal secondaries. A prospective, randomized study
      should be undertaken to clarify the respective roles of therapeutic irradiation
      and surgery for metastatic tumors of the axial spine.

PMID- 1379831
TI  - Prostatic cancer: are we closer to rational treatment selection?
AB  - Despite the controversies in management for all stages of prostatic cancer,
      guidelines are emerging that allow for better selection of treatments for
      individual patients. For early stage disease, prostate-specific antigen
      determinations in conjunction with other staging procedures have refined our
      ability to define truly organ-confined disease. The more widespread use of
      laparoscopic lymph node dissections has spared many patients needless
      laparotomies. For patients with metastatic disease, the overall effect of potency
      sparing antiandrogens as monotherapy needs to be investigated. Most encouraging
      is that more groups are using prostate-specific antigen changes to assess disease
      activity and the rapid translation of recent laboratory investigations into the
      clinic. As our ability to predict the biologic potential of an individual
      patient's tumor is improved, more individualized treatment recommendations will
      be possible.

PMID- 1379833
TI  - Current concepts in leptomeningeal metastasis.
AB  - Leptomeningeal metastasis is a common neurologic disorder affecting the entire
      neuraxis in patients with metastatic systemic cancer and primary brain tumors.
      The clinical presentation of leptomeningeal metastasis is pleomorphic and
      commonly affects the cerebral hemispheres, cranial nerves, or spinal cord and its
      roots. Diagnosis is confirmed by the presence of malignant cells in the
      cerebrospinal fluid or by clinical and neuroradiographic pattern compatible with
      leptomeningeal metastasis. Treatment is palliative and is directed at the entire
      neuraxis combining involved-field radiotherapy and intra-cerebrospinal fluid drug
      administration. Regional chemotherapy pharmacokinetically is best administered by
      intraventricular instillation employing frequent drug administration, thereby
      insuring prolonged cytotoxic drug exposure. Chemotherapeutic drug distribution is
      dependent on bulk flow of cerebrospinal fluid. This review will summarize current
      information regarding the incidence, clinical presentation, laboratory findings,
      pathology, pathophysiology, staging, treatment, and survival of patients with
      leptomeningeal metastasis.

PMID- 1379834
TI  - [Sepsis caused by Mycobacterium tuberculosis in patients with AIDS].
AB  - BACKGROUND: Techniques for detecting mycobacteria in blood can be a good
      alternative for diagnosing tuberculosis in acquired-immunodeficiency syndrome
      patients (AIDS). PATIENTS AND METHODS: Eleven patients with AIDS and pulmonary
      tuberculosis, and four controls with AIDS and without tuberculosis were studied.
      The diagnosis of mycobacteremia was made by the identification of the
      microorganisms in blood. The method used was a lysis-centrifugation with
      subsequent stain or culture identification in different media (agar Lowenstein
      Jensen, M7H9, M7H11, brain-heart infusion and Sauton broth). RESULTS: In one
      case, direct staining of sample was positive. The culture results were positive
      in all 11 patients with tuberculosis and in none of the controls. M7H11 was the
      media that allows the fastest detection. CONCLUSIONS: This technique can be a
      good alternative method for tuberculosis diagnosis in AIDS patients. Is easy to
      perform, relatively fast an with diagnostic performance. It also could be of
      interest in extra-pulmonary tuberculosis.

PMID- 1379835
TI  - Monoclonal antibodies to soluble human TNF receptor (TNF binding protein) enhance
      its ability to block TNF toxicity.
AB  - A soluble extracellular fragment of the human 55-60 kDa tumor necrosis factor
      receptor (sTNF-R I), originally isolated from urine, binds both TNF-alpha and TNF
      beta and blocks the activity of these cytokines in biological assays. Three
      monoclonal antibodies (mAbs) raised against sTNF-R I (TBP-1, -2 and -6) as well
      as a mAb developed by immunization with the intact receptor (H398) were analysed
      for their epitope specificities in ELISAs and for biological activity in
      cytotoxicity assays on murine L-M cells. TBP-2 and H398 bind to related epitopes
      on sTNF-R I; they compete with TNF-alpha for binding and block the protective
      effect of sTNF-R I in the bioassay. MAbs TBP-1 and TBP-6 recognize two further,
      independent epitopes; both bind sTNF-R I in the presence of an excess of TNF
      alpha. Both TBP-1 and TBP-6 markedly enhance the ability of sTNF-R I to protect
      cells against the cytotoxic activities of TNF-alpha and TNF-beta, but have no
      activity in the absence of sTNF-R I. Fab fragments show much lower activity. We
      propose that the ability of certain mAbs to enhance the protective activity of
      sTNF-R is due to a steric hindrance phenomenon.

PMID- 1379836
TI  - Abrogation of the antiproliferative activity of oncostatin M by a monoclonal
      antibody.
AB  - Oncostatin M (OM) is a novel cytokine which exhibits pleiotropic effects on a
      wide variety of normal and transformed cell lines. To determine some of the
      physiological functions of OM we have characterized several monoclonal antibodies
      to the recombinant molecule. Antibodies OM1 and OM2 bound native, but not
      denatured OM, suggesting they recognize non-contiguous epitopes. A third
      antibody, OM6, bound predominantly denatured OM. Of the two antibodies which
      detect discontinuous epitopes, OM2, but not OM1, was identified as a neutralizing
      antibody based on its ability to abrogate OM activity in the growth inhibition
      assay (GIA) and to inhibit OM binding in the radioreceptor assay (RRA). OM2 was
      equally effective in abrogating the functional effects of either natural or
      recombinant OM, thereby demonstrating that the active sites of these molecules
      are structurally similar, if not identical.

PMID- 1379837
TI  - Electrochemotherapy tumor treatment is improved by interleukin-2 stimulation of
      the host's defenses.
AB  - We have recently described a new antitumor treatment, electrochemotherapy (ECT),
      based on the large local potentiation of the effects of the chemotherapeutic
      agent bleomycin (BLM) by electric pulses (EP) delivered at the tumor site. We
      demonstrate here that the host's immune response participates in cure
      achievement. We obtain an increase of the rate of completely cured animals by
      injecting mice with interleukin-2 (IL-2).

PMID- 1379838
TI  - Hypothesis: the target cell of GM-CSF is a macrophage precursor capable to
      produce cells with the property to secrete a G-CSF like activity.
AB  - The induction of granulocyte and macrophage colony formation by the granulocyte
      macrophage colony stimulating factor (GM-CSF) on bone marrow cells (BMC) was
      evaluated as a function of time in agar cultures. We found that while macrophage
      cell clusters were very abundant on the first two days of culture, granulocytic
      cell clusters did not appear until the third day. We also found that macrophage
      colonies were present from the fourth day of culture, while granulocyte colonies
      did not appear until the fifth day. When two day cell clusters were transferred
      to cultures with GM-CSF we observed that only macrophage-colonies developed. On
      the other hand, when four day clusters were transferred, both granulocyte and
      macrophage colony formation was obtained in a similar way as the one obtained
      when using GM-CSF with fresh BMC. Two day clusters did not respond to granulocyte
      colony stimulating factor (G-CSF) while fourth day clusters generated
      granulocytic colonies in a similar way as when G-CSF was used with fresh BMC. In
      order to test the hypothesis that granulocyte colony formation in these assays
      could be a result of the secretion of G-CSF by the macrophages previously induced
      by GM-CSF, lysates from macrophage colonies were used to induce colony formation
      on BMC. We observed that colonies, mainly granulocytic, were induced in a similar
      way as when G-CSF was used. Finally, the possibility that GM-CSF is just a
      macrophage inducer with the property to produce cells that secrete G-CSF is
      discussed.

PMID- 1379839
TI  - Distribution kinetics of FK-506, a novel immunosuppressant, after intravenous
      administration to rats in comparison with cyclosporin A.
AB  - The distribution kinetics of a novel potent immunosuppressant, FK-506 (FK) has
      been studied in comparison with cyclosporin A (CyA) both in vivo and in vitro
      using blood specimens. The infusion studies on FK, 5.0 mg kg-1 through the portal
      and femoral veins showed that the mean hepatic extraction ratio of FK was 27.9
      per cent. The effect of clamping both the hepatic artery and the portal vein on
      the plasma disappearance profiles of FK, 5.0 mg kg-1, and CyA, 3.5 mg kg-1 was
      studied. The plasma disposition kinetics of CyA was almost the same as in the
      normal rats. However, the plasma FK levels were about 10 times higher than those
      obtained in the control group rats. This difference is attributed to the
      restricted initial distribution of FK to the liver, because the volume of the
      initial distribution space, V1, of FK was about 10 times smaller than that
      obtained in normal rats. In in vitro experiments, drug distribution was studied
      in blood samples (2.0 ml) spiked with FK or CyA, 1.0 micrograms ml-1. The plasma
      drug levels measured at 2 min after drug administration were 0.842 +/- 0.012
      micrograms ml-1 and 0.769 +/- 0.047 micrograms ml-1 for FK and CyA, respectively.
      The distribution volume in the blood compartment, VB, was determined by dividing
      the spiked amount of drugs with these plasma concentrations. The VB was 2.38 +/-
      0.04 ml for FK and 2.62 +/- 0.16 ml for CyA. There was no significant difference
      in VB between FK and CyA. The plasma free fraction, fp of the drugs was measured
      by the equilibrium dialysis method. For FK, the mean fp values (+/- SE) were 1.31
      +/- 0.18 per cent (2.0 micrograms ml-1) and 1.93 +/- 0.18 per cent (5.0
      micrograms ml-1). For CyA, the fp values were 4.85 +/- 0.36 per cent (1.0
      micrograms ml-1) and 5.75 +/- 0.82 per cent (5.0 micrograms ml-1). The
      hydrophobicity parameter, logP' determined through the HPLC method was 0.386 for
      FK and 0.545 for CyA. Although FK was less hydrophobic than CyA, its protein
      binding was higher than CyA.

PMID- 1379840
TI  - 'In vitro' action of histamine and cimetidine on amylase secretion in the rat
      pancreas.
AB  - We report here the effect of histamine on amylase secretion in isolated lobules
      from the rat pancreas. Different concentrations of histamine increased amylase
      secretion, while the stimulatory effect was reduced by cimetidine although not by
      chlorpheniramine. These findings suggest that pancreatic lobules have H2
      receptors. On the other hand, bethanechol induced a stimulatory effect on
      pancreatic lobules that was inhibited by cimetidine. Vibrio cholerae toxin
      stimulated amylase secretion, but this effect was not reduced by cimetidine.
      Cimetidine may thus block the stimulated amylase secretion interfering with the
      Ca2+ messenger system.

PMID- 1379841
TI  - Cyclosporin A, FK506, rapamycin: the use of a quantitative analytic tool to
      discriminate immunosuppressive drug interactions.
AB  - Potent immunosuppressive agents display toxic complications at full therapeutic
      doses: cyclosporin A (CsA) produces pleiotropic mesenchymal effects with
      prominent vasculopathy, whereas FK506 displays severe neurotoxicity associated
      with a similar range of mesenchymal and possibly vasculitic reactions. The
      concept of drug synergy seeks to exploit combinations of agents that promote each
      other's immunosuppressive effects. This article presents a quantitative method to
      assess synergy in vitro and in vivo--the median-effect analysis. Application of
      this method revealed synergistic interactions of CsA with steroids, an additive
      effect with azathioprine, and antagonistic effects with FK506 and enisoprost.
      Clearly, a synergistic therapeutic combination can be clinically useful only if
      it is not associated with a similar potentiation of toxic complications. Clinical
      practice has documented the synergistic relation of CsA plus steroids and the
      antagonistic relation of CsA with FK506 or enisoprost. Clinical trials of
      rapamycin, which displays extremely potent synergistic effects with CsA both in
      vitro with human and in vivo with animal immune responses, may afford important
      new insights for clinical immunosuppression.

PMID- 1379842
TI  - Effect of aprotinin on plasma fibronectin levels in patients undergoing
      cardiopulmonary bypass.

PMID- 1379843
TI  - Differences in tyrosine phosphorylated proteins between cells expressing
      P210bcr/abl and P190bcr/abl.
AB  - We analysed differences between the populations of tyrosine phosphorylated
      proteins in two cell lines, K-562 and MR-87, which express two different bcr-abl
      fusion gene products, using both immunoprecipitation and Western blotting with an
      anti-phosphotyrosine antibody. K-562 cells preferentially expressed P210bcr/abl
      (P210), while MR-87 expressed P190bcr/abl (P190). Tyrosine phosphorylated
      proteins with a molecular mass of 150 kDa (p150) and 115 kDa (p110) were found in
      both K-562 and MR-87. A 36 kDa protein (p36) was tyrosine phosphorylated in vivo
      only in K-562 cells, while proteins with a molecular mass of 140 kDa (p140) and
      62 kDa (p62) were found only in MR-87 cells. Moreover, several proteins in the
      detergent-insoluble cell fraction were differently tyrosine phosphorylated in
      vitro in K-562 and MR-87 lysates. These results suggest that P210 and P190 may
      have different substrates, and thus, different signal transduction pathways for
      cell proliferation, although the differential association of such cellular
      proteins with the two bcr/abl products remains to be clarified.

PMID- 1379844
TI  - Treatment of acute nonlymphocytic leukemia by combination of recombinant human
      granulocyte colony-stimulating factor and cytotoxic agents: a report of six
      cases.
AB  - Six patients with recurrent and/or refractory acute nonlymphocytic leukemia
      (ANLL) were treated with recombinant human granulocyte colony-stimulating factor
      (G-CSF) and cytotoxic agents administered simultaneously. Neither of the two
      patients who received cytosine arabinoside (ara-C) in combination with G-CSF
      achieved complete remission. The other four patients, who received multi-drug
      combination therapy together with G-CSF, all achieved complete remission. No
      major side effects due to G-CSF were observed. These results demonstrated that
      the effects of G-CSF in enhancing the sensitivity of leukemic cells to cytotoxic
      agents and accelerating the recovery of leukocytes could lead to its possible use
      in the treatment of ANLL.

PMID- 1379845
TI  - Recombinant acidic human fibroblast growth factor (aFGF) stimulates murine
      megakaryocyte colony formation in vitro.
AB  - Recombinant acidic human fibroblast growth factor (aFGF) significantly stimulated
      the formation of megakaryocyte colonies and the size of MK colonies as well as
      individual MKs in vitro in mice. When aFGF was combined with recombinant mouse
      interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF)
      or interleukin-6 (IL-6) at their optimal doses, a synergistic action was found
      between aFGF and IL-3. The activity of aFGF could be completely abrogated by a
      monoclonal antimouse IL-6 antibody which specifically neutralized the action of
      mouse IL-6 but not human IL-6. These data indicate that aFGF provides positive
      growth signals of megakaryocyte progenitor cells, which can give rise to a
      synergistic action in the presence of IL-3 and which can be abrogated by the
      antimouse IL-6 antibody.

PMID- 1379846
TI  - Expression of two types of kit ligand mRNAs in human tumor cells.
AB  - The primary structure of human kit ligand (KL) growth factor mRNA was analyzed by
      polymerase chain reaction (PCR) and nucleotide sequencing. Two bands from the
      total RNAs of a variety of human tumor cell lines were amplified by RT-PCR.
      Nucleotide sequences of these cloned cDNAs revealed that an 84-nucleotide
      stretch, corresponding to a spacer chain which contains the site for proteolytic
      release of the cytokine domain, was missing in the shorter clone, resulting in a
      transmembrane-bound form of KL. The relative intensity of the two bands in human
      bone marrow and tumor cells was then determined. In the bone marrow cells, THP1
      and HuH7, the band for the membrane-bound type of KL was relatively more intense,
      whereas the reverse was the case in Daudi, K562 and HT1080 cells, suggesting that
      there are variations in the expression level of these two human KL mRNAs.

PMID- 1379847
TI  - Phenotypic changes induced by interleukin-2 (IL-2) and IL-3 in an immature T
      lymphocytic leukemia are associated with regulated expression of IL-2 receptor
      beta chain and of protein tyrosine kinases LCK and LYN.
AB  - We have previously reported the establishment of an interleukin-3 (IL-3)
      dependent and phenotypically myeloid cell line (TALL-103/3), obtained by
      culturing cells from an immature T-lymphoblastic leukemia in the presence of IL
      3. These cells differentiated into a T-lymphoid cell line (TALL-103/2) upon
      removal of IL-3 and incubation in IL-2. Despite the different phenotype, the two
      cell lines remained karyotypically and genotypically identical. Here, we have
      analyzed the phenotypic changes and the signaling events induced by these two
      lymphokines in TALL-103/3 cells by switching them to temporary growth in IL-2 and
      returning them to IL-3. All four sublines obtained (the myeloid in IL-3 and the
      lymphoid in IL-2) expressed RNA for CD3, IL-2 receptor (R) alpha, and T-cell
      receptor (TCR)-gamma and -delta chains. However, cells cultured in IL-3 failed to
      express detectable levels of the IL-2R beta chain at both the protein and RNA
      levels, whereas cells exposed to IL-2 always expressed IL-2R beta. In parallel
      with the changes in IL-2R beta expression, the SRC-like protein tyrosine kinase
      (PTK) p56 LCK could not be detected in IL-3-dependent cells, but was abundant in
      the IL-2-dependent cells and underwent markedly increased autophosphorylation in
      response to IL-2. In contrast, p53/p56 LYN was highly expressed in IL-3-dependent
      cells, and greatly decreased when these cells were switched to growth in IL-2.
      LYN kinase autophosphorylation modestly increased in response to IL-3. None of
      the other kinases in the SRC family that were tested underwent increased
      autophosphorylation after lymphokine stimulation, indicating the specificity of
      IL-2 for LCK and of IL-3 for LYN. The TALL-103 cell lines provide a unique system
      to study the interaction between lymphokines and SRC-family PTKs in signal
      transduction pathways leading to hematopoietic cell differentiation.

PMID- 1379848
TI  - OMA-AML-1: a leukemic myeloid cell line with CD34+ progenitor and CD15+
      spontaneously differentiating cell compartments.
AB  - OMA-AML-1 was established from a patient with acute myelomonocytic (M4) leukemia
      at fifth relapse when blasts were greater than 85% CD34+, CD15-. Leukemic cells
      were established in suspension culture and independently grown as subcutaneous
      tumors in SCID mice. Cells growing in suspension culture underwent
      differentiation by phenotypic and morphologic criteria. In contrast, cells grown
      as subcutaneous solid tumors in SCID mice maintained progenitor cell
      characteristics with high-density CD34 expression and lack of morphologic
      differentiation. A tendency toward differentiation to CD15+, CD34- cells in vitro
      and self-renewal of CD34+, CD15- cells in vivo was consistently demonstrated
      regardless of whether cells were initially grown in vitro or in vivo. The cell
      line maintains both a CD34+, CD15- progentitor cell pool and a non-overlapping,
      CD15+, CD34- differentiating cell compartment after more than 1 year in
      continuous culture. Cell cycle analysis and cloning experiments were consistent
      with terminal differentiation occurring in the CD15+, CD34- population. The cell
      line shows concentration-dependent proliferative responses to interleukin (IL)-3,
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6, but not to
      granulocyte CSF (G-CSF). OMA-AML-1 appears to mimic several features of normal
      myeloid hematopoiesis and should prove useful for the study of normal and
      malignant myeloid differentiation.

PMID- 1379849
TI  - Crossreacting human lymphoma idiotypes.
AB  - We have examined an unselected series of 72 lymphomas of diverse histologies with
      a panel of mouse monoclonal antibodies specific for human B-lymphoma-derived Ig
      idiotypes (anti-ids) to determine the nature and extent of id/anti-id
      crossreactivity. The anti-id antibodies were prepared from Ig isolated from seven
      follicular center cell lymphomas by heterohybridoma technique. Thirty-six of 75
      individual anti-ids obtained in this manner were further selected based on their
      reactivity with highly restricted or private idiotypic determinants. Twelve of
      the 72 (17%) lymphoma biopsies reacted with one or more of the 36 anti-ids that
      detect private determinants. A pool consisting of five individual antibodies
      would have detected 11 of the 12 crossreacting tumors. Staining of tumor cell
      populations was homogeneous in the positive cases, suggesting uniform idiotype
      expression. If there was a segregated staining pattern, it was generally related
      to the presence of CD3+ T cells in the section. These follicular center cell
      derived anti-ids cross-reacted with follicular center cell tumors of all
      histologic grades with frequencies ranging from 13% to 50%. The structural basis
      for the crossreactivity of our lymphoma-derived private anti-ids is as yet not
      known. However, the reactivity of certain anti-ids with both kappa- and lambda
      expressing tumors suggests a biased use of V gene segments in these crossreactive
      clones that is probably related to the VH gene. These data suggest the
      possibility that lymphoma may develop in a highly restricted pool of normal
      differentiated B cells or in B-cell subsets that express a limited repertoire of
      unmutated VH gene segments.

PMID- 1379850
TI  - Multiple Rh messenger RNA isoforms are produced by alternative splicing.
AB  - Three Rh-related cDNAs have been isolated from a human bone marrow cDNA library
      and by polymerase chain reaction (PCR) amplification of human bone marrow and
      erythroblast mRNAs. They potentially encode a family of Rh protein isoforms that
      exhibit several unexpected structural properties as compared with the Rh
      polypeptide encoded by the cDNA clone identified previously. These modifications
      include several peptide deletions, the predicted alteration of Rh protein
      topology within the cell membrane, variations in the number and surface
      exposition of cysteine residues, and the generation of new C-terminal polypeptide
      segments caused by frameshift mutations. The four Rh mRNAs now described
      correspond to different splicing isoforms transcribed from the same Rh gene, and
      all exist in the same cell lineage (erythroid). Moreover, PCR experiments
      indicated that at least three of these RNA species exist in reticulocytes from
      donors with different commonly expressed Rh phenotypes. Although the translated
      proteins have not yet been characterized, these results suggest that the two
      genes at the RH locus may direct the synthesis of several protein species
      possibly corresponding to different Rh antigenic variants.

PMID- 1379851
TI  - CD5+, CD11C+, trap-positive chronic lymphocytic leukemia/prolymphocytic leukemia.

PMID- 1379852
TI  - Evidence that stem cell factor is involved in the rebound thrombocytosis that
      follows 5-fluorouracil treatment.
AB  - The mechanisms responsible for 5-fluorouracil (5FU)-induced rebound
      thrombocytosis are not completely understood. SI/SI(d) mice, which do not undergo
      rebound thrombocytosis in response to 5FU, provide a genetic approach to the
      study of this phenomenon. Recent reports by several groups that the SI locus
      encodes a protein known variably as stem cell factor (SCF), mast cell growth
      factor, or kit ligand, suggests the possibility that the lack of wild-type SCF in
      SI/SI(d) mice is responsible for their defective response to 5FU-induced
      thrombocytopenia. It is shown in this report that SCF-treated SI/SI(d) mice are
      as capable as their wild-type littermates in undergoing rebound thrombocytosis.
      W/Wv mice, mutated at the locus encoding the SCF receptor, also do not undergo
      rebound thrombocytosis, but are not responsive to SCF treatment. In normal mice,
      it is shown by RNA solution hybridization that SCF mRNA expression is increased
      during the 5FU-induced platelet nadir period. It is also shown by autoradiography
      that maturing megakaryocytes express SCF receptors, and that in vivo
      administration of SCF significantly raises the numbers of megakaryocytes, as well
      as circulating platelet counts. Taken together, these data indicate that SCF may
      be an important regulator of platelet production under both normal and
      physiologically disturbed situations.

PMID- 1379853
TI  - A c-kit ligand, recombinant human stem cell factor, mediates reversible expansion
      of multiple CD34+ colony-forming cell types in blood and marrow of baboons.
AB  - The ligand for the human c-kit, recombinant human stem cell factor (SCF), was
      administered to baboons at doses of 200, 100, 50, 25, and 10 micrograms/kg/d. SCF
      induced a dose-dependent expansion of hematopoietic colony-forming cells (CFC) of
      multiple types in both blood and marrow, including colony-forming unit (CFU)
      granulocyte-monocyte, burst-forming unit-erythroid, CFU-MIX, and high
      proliferative potential-CFC. These changes were associated with a dose-dependent
      leukocytosis, involving all leukocyte lineages, a reticulocytosis, and increases
      in marrow cellularity. At 200 micrograms/kg/d of SCF, CFC in blood were increased
      10-fold to greater than 100-fold. This correlated with an increased frequency of
      CD34+ cells in blood. The frequency of CFC in blood approached that of marrow in
      some animals. These changes were reversed within 7 to 14 days of stopping SCF.
      The results of these studies suggest a role for the c-kit ligand in stimulating
      the expansion of multiple CFC types in blood and marrow for potential therapeutic
      purposes.

PMID- 1379854
TI  - Effects of bone marrow stimulatory cytokines on human immunodeficiency virus
      replication and the antiviral activity of dideoxynucleosides in cultures of
      monocyte/macrophages.
AB  - Cells of the monocyte lineage are important targets for the replication of human
      immunodeficiency virus (HIV). Our group and others have previously shown that
      granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates HIV
      replication in monocyte/macrophages, but that it also enhances the anti-HIV
      activity of 2',3'-dideoxy-3'-azidothymidine (AZT). In the present study, we have
      explored the effects of other bone marrow stimulatory cytokines on the
      replication of HIV and on the anti-HIV activity of certain dideoxynucleosides in
      human peripheral blood monocyte/macrophages (M/M). Like GM-CSF, macrophage CSF (M
      CSF) enhanced HIV replication in M/M. In contrast, granulocyte CSF (G-CSF) and
      erythropoietin (Epo) had no such effects. The anti-HIV activity of zidovudine
      (AZT) was increased in M/M exposed to GM-CSF. In contrast, the anti-HIV activity
      of AZT was unchanged in M/M exposed to M-CSF, and the activities of 2',3'
      dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddl) were unchanged or slightly
      diminished in M/M stimulated with GM-CSF or M-CSF. These differential activities
      of AZT and ddC were paralleled by differential effects of the cytokines on the
      anabolism of these drugs to their active 5'-triphosphate moieties. GM-CSF
      increased the levels of AZT-5'-triphosphate (at least in part through an increase
      in thymidine kinase activity) and overall induced an increase in the ratio of AZT
      5'-triphosphate/thymidine-5'-triphosphate. In contrast, M-CSF-induced increases
      in AZT-5'-triphosphate were roughly matched by increases in thymidine-5'
      triphosphate. Also, GM-CSF- or M-CSF-induced increases in the levels of ddC-5'
      triphosphate were associated with parallel increases in the levels of
      deoxycytidine-5'-triphosphate (the physiologic nucleoside that competes at the
      level of reverse transcriptase), so that there was relatively little net change
      in the ddC-5'-triphosphate/deoxycytidine-5'-triphosphate ratio. Thus, bone marrow
      stimulatory cytokines may have a variety of effects on HIV replication and on the
      activity and metabolism of dideoxynucleosides in M/M.

PMID- 1379855
TI  - Calcium pools mobilized by calcium or inositol 1,4,5-trisphosphate are
      differentially localized in rat heart and brain.
AB  - Calcium-induced calcium release (CICR) pools have been demonstrated in brain and
      heart microsomes biochemically and autoradiographically by the sensitivity of
      45Ca2+ accumulation to Mg2+, ATP, ruthenium red, caffeine, and tetracaine. The
      CICR pool colocalizes with [3H]ryanodine binding sites, supporting the notion
      that [3H]ryanodine labels CICR pools. Sites of CICR pools in the brain contrast
      with those of inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ pools with
      reciprocal localizations between the two Ca2+ pools in several structures. Thus,
      in the hippocampus CA-1 is enriched in IP3-sensitive Ca2+ pools, whereas CICR
      pools are highest in CA-3 and the dentate gyrus. The corpus striatum and
      cerebellum are enriched in IP3 pools, whereas the medial septum and olfactory
      bulb have high CICR densities. In cardiac tissue, CICR is localized to atrial and
      ventricular muscle, whereas IP3 pools are concentrated in coronary vessels and
      cardiac conduction fibers. The reciprocal enrichment of IP3 and CICR Ca2+ pools
      implies differential regulation of Ca2+ hemostasis in these tissues.

PMID- 1379857
TI  - Antitumor action of retinoids: inhibition of tumor cell line-induced angiogenesis
      and prevention of tumors in mice.
AB  - Acitretin was shown to inhibit angiogenic response to the tumorigenic SKV cell
      line bearing HPV16 genome and to sarcoma L-1 cell line, both in vitro and in vivo
      systems. The lowered angiogenic response to tumor cells was independent of
      duration and timing of the application of acitretin to animals. Acitretin, but
      not etretinate, was also found to be effective in the prevention of sarcoma
      tumors in mice.

PMID- 1379856
TI  - The yeast Ca(2+)-ATPase homologue, PMR1, is required for normal Golgi function
      and localizes in a novel Golgi-like distribution.
AB  - PMR1, a Ca(2+)-adenosine triphosphatase (ATPase) homologue in the yeast
      Saccharomyces cerevisiae localizes to a novel Golgi-like organelle. Consistent
      with a Golgi localization, the bulk of PMR1 comigrates with Golgi markers in
      subcellular fractionation experiments, and staining of PMR1 by indirect
      immunofluorescence reveals a punctate pattern resembling Golgi staining in yeast.
      However, PMR1 shows only partial colocalization with known Golgi markers, KEX2
      and SEC7, in double-label immunofluorescence experiments. The effect of PMR1 on
      Golgi function is indicated by pleiotropic defects in various Golgi processes in
      pmr1 mutants, including impaired proteolytic processing of pro-alpha factor and
      incomplete outer chain glycosylation of invertase. Consistent with the proposed
      role of PMR1 as a Ca2+ pump, these defects are reversed by the addition of
      millimolar levels of extracellular Ca2+, suggesting that Ca2+ disposition is
      essential to normal Golgi function. Absence of PMR1 function partially suppresses
      the temperature-sensitive growth defects of several sec mutants, and
      overexpression of PMR1 restricts the growth of others. Some of these interactions
      are modulated by changes in external Ca2+ concentrations. These results imply a
      global role for Ca2+ in the proper function of components governing transit and
      processing through the secretory pathway.

PMID- 1379858
TI  - Carbohydrate masking of an antigenic epitope of influenza virus haemagglutinin
      independent of oligosaccharide size.
AB  - Comparison of the haemagglutinins (HA) of the pathogenic avian influenza viruses
      A/FPV/Dutch/27 (H7N7) and A/FPV/Rostock/34 (H7N1) revealed 94.7% nucleotide and
      93.8% amino acid sequence homologies. Six of the seven N-glycosidic
      oligosaccharides of the Rostock HA are at the same positions as the six
      carbohydrates of the Dutch strain. The additional oligosaccharide side chain of
      the Rostock strain, which is of the complex type, is attached to asparagine149 in
      antigenic epitope B. The accessibility of this antigenic epitope has been
      analysed by using rabbit antisera raised against synthetic peptides comprising
      amino acids 143-162. The carbohydrates of the HA of the Rostock strain have been
      modified (i) to truncated cores by expression in insect cells using a baculovirus
      vector, (ii) to oligomannosidic side chains by growth in the presence of the
      trimming inhibitor methyldeoxynojirimycin and (iii) to a single N
      acetylglucosamine residue by removal of the oligomannosidic sugar with endo-beta
      N-acetylglucosaminidase H. Neither the authentic nor the modified
      oligosaccharides allowed antibody binding, as indicated by enzyme-linked
      immunosorbent assay (ELISA) and Western blot analyses. Reactivity was observed,
      however, after complete removal of the carbohydrate from HA of the Rostock strain
      by digestion with peptide-N-glycosidase F. HA of the Dutch strain was reactive
      without prior peptide-N-glycosidase F treatment. These results demonstrate that a
      single N-acetyl-glucosamine at asparagine149 is sufficient to prevent recognition
      of the peptide epitope.

PMID- 1379859
TI  - Natural killer cell surface markers on cells containing parallel tubular
      structures.
AB  - Parallel tubular structures (PTS) and/or the associated electron-dense granules,
      thought to contain molecules responsible for target cell lysis, can be detected
      in the cytoplasm of lymphocytes with large granular lymphocyte (LGL) morphology.
      In the present study we compared PTS presence in freshly isolated peripheral
      blood lymphocytes and peripheral blood lymphocytes incubated overnight in the
      presence of human pooled serum, sera from patients with Hodgkin's disease and
      interferon-alpha. Under all conditions we found PTS in the majority of CD16+
      cells (64.3-74.8%) but less than 41.8% in CD57+ cells. In the case of double
      labeled lymphocytes, 41.0-61.7% CD16+/8+ but only 24.2-27.5% CD57+/8+ cells were
      PTS+. Thus, in all cases where lymphocytes expressed CD16 antigen there was a
      high percentage of PTS positivity. Although the PTS+ cells exhibited phenotypic
      heterogeneity there was, except for a proportion of CD57+ lymphocytes which
      exhibited less of the characteristic LGL features, generally LGL morphological
      homogeneity. CD16 lymphocytes are potentially more cytotoxic than CD57 and CD8
      cells. Taking this into consideration, the presence of the PTS in the majority of
      CD16 cells suggests an important role for PTS in target cell lysis.

PMID- 1379860
TI  - [Comparative study of chuanxiong and dextran 40 in the treatment of acute
      cerebral infarction].
AB  - This paper reports the results of a double-blind trial in 220 patients with acute
      cerebral infarction evidenced by CT, who were randomly divided into ligusticum
      chuanxiong group (134 cases) and low molecular weight dextran group (86 cases). A
      weighted scoring system was adopted to evaluate the neurologic function and
      living capability. The results showed that the total therapeutic efficacy rate in
      chuanxiong group and in dextran 40 group were 86.6% and 62.8% respectively. The
      effect of chuanxiong on the treatment of acute cerebral infarction was superior
      to low molecular weight dextran and the difference between the two groups was
      statistically significant (P less than 0.01).

PMID- 1379861
TI  - [Prevention of post-transfusion non-A, non-B hepatitis by anti-HCV screening].
AB  - Since May 1990 a specific enzyme immunoassay (EIA) for NANBH has been developed
      by recombinant DNA technology which detects antibodies to a virus called
      hepatitis C virus (HCV). The anti-HCV EIA was manufactured by Ortho-Diagnostic
      Systems with recombinant antigens from Chiron Corp. based on extraction from high
      infectious titre chimpanzee plasma RNA after transcription into cDNA. We tested
      the anti-HCV prevalence of blood donors and hemodialysis patients. The anti-HCV
      prevalence with the first generation test was 0.52% (Ortho), 0.87% (Abbott) in
      blood donors and 4.16% in hemodialysis patients. The second generation anti-HCV
      test (Abbott) with improved sensitivity and specificity comprises 0.25% repeated
      anti-HCV positive blood donors and 8.2% anti-HCV positive hemodialysis patients.

PMID- 1379862
TI  - The ciliary body--the third organ found to synthesize indoleamines in humans.
AB  - Indoleamines are associated with circadian rhythms in pineal gland and retina.
      Because the ciliary epithelium has an embryonic origin similar to that of pineal
      gland and retina, and intraocular pressure shows circadian variations,
      indoleamines were searched for in aqueous humor and ciliary body in humans. In
      aqueous humor, serotonin, 6-hydroxymelatonin, and melatonin were simultaneously
      detected and measured using high-performance liquid chromatography with
      electrochemical detection. The concentration was 48.7 +/- 10.9 ng/ml for
      serotonin, 0.47 +/- 0.8 ng/ml for melatonin, and 13.9 +/- 7.7 ng/ml for 6
      hydroxymelatonin. In ciliary bodies from freshly enucleated human eyes,
      tryptophan, 5-hydroxytryptophan, serotonin, and 5-hydroxyindoleacetic acid were
      detected using high-performance liquid chromatography with simultaneous
      fluorescence- and electrochemical detection. Finally, the enzymatic activities of
      arylalkylamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase
      (HIOMT), enzymes indispensable in the synthesis of melatonin, were measured. The
      NAT activity was 273 +/- 25 pmol/mg protein/hour and that of HIOMT, 13520 +/- 50
      pmol/mg protein/hour in ciliary body. Comparison of these activities (NAT versus
      HIOMT) permits the suggestion that NAT is a limiting enzyme in serotonin
      metabolism in this tissue. These findings indicate that a circadian rhythm of
      indoleamines exists in human aqueous humor and that the human ciliary body is the
      third organ, after the pineal gland and the retina, found to synthesize
      indoleamines in humans.

PMID- 1379863
TI  - Intrachoroidal dye leakage in indocyanine green fundus angiography after
      experimental commotio retinae.
AB  - Dye leakage in sodium fluorescein (FLUO) fundus angiography indicates damage to
      the blood-retinal barrier. However, dye leakage in indocyanine green (ICG) fundus
      angiography does not mean the same, because of the larger molecular size of the
      dye and impermeability of the choroidal vessels to it. The possibility of dye
      leakage in ICG angiography has not yet been revealed in an experimental study in
      which the blood-retinal barrier is undamaged. We report here that intrachoroidal
      dye leakage may occur in ICG angiography in an experimental model of the
      traumatic retinal opacity of the rabbit eye, even when the blood-retinal barrier
      is undamaged. This mechanism of dye leakage in ICG angiography is quite different
      from the leakage of FLUO angiography. Pathological choroidal vessels with
      increased permeability, such as choroidal neovascularization under the retinal
      pigment epithelium, can be observed using ICG angiography.

PMID- 1379864
TI  - The pea ferredoxin I gene exhibits different light responses in pea and tobacco.
AB  - We monitored Fed-1 (encoding ferredoxin I) mRNA levels in etiolated transgenic
      tobacco seedlings containing the intact pea Fed-1 gene to determine if the
      characteristic light responses of this gene in pea seedlings are also observed in
      transgenic tobacco. Fed-1 transcript levels in transgenic tobacco seedlings
      closely paralleled those of the native gene in pea buds when etiolated seedlings
      were transferred to white light. However, the response to red light was much
      smaller in tobacco than in pea and was not efficiently reversed by far-red light.
      The red light response of endogenous tobacco ferredoxin transcripts is closely
      comparable to that of the Fed-1 transgene, with a similar lack of
      photoreversibility. Thus, the pea Fed-1 transgene responds normally to tobacco
      gene-regulatory factors, but these factors are less influenced by phytochrome in
      tobacco cotyledons than in pea buds.

PMID- 1379866
TI  - Acute phase proteins: their use in veterinary diagnosis.

PMID- 1379865
TI  - Visualization and characterization of tobacco mosaic virus movement protein
      binding to single-stranded nucleic acids.
AB  - Cell-to-cell spread of tobacco mosaic virus (TMV) is presumed to occur through
      plant intercellular connections, the plasmodesmata. Viral movement is an active
      process mediated by a specific virus-encoded P30 protein. P30 has at least two
      functions, to cooperatively bind single-stranded nucleic acids and to increase
      plasmodesmatal permeability. Here, we visualized P30 complexes with single
      stranded DNA and RNA. These complexes are long, unfolded, and very thin (1.5 to
      2.0 nm in diameter). Unlike TMV virions (300 x 18 nm), the complexes are
      compatible in size with the P30-induced increase in plasmodesmatal permeability
      (2.4 to 3.1 nm), making them likely candidates for the structures involved in the
      cell-to-cell movement of TMV. Mutational analysis using single and double
      deletion mutants of P30 revealed three regions potentially important for the
      protein function. Amino acid residues 65 to 86 possibly are required for correct
      folding of the active protein, and the regions between amino acid residues 112 to
      185 and 185 to 268 potentially contain two independently active single-stranded
      nucleic acid binding domains designated binding domains A and B, respectively.

PMID- 1379867
TI  - Expression of GABAA receptor polypeptides in clonal rat cell lines.
AB  - The neuronal-like cell lines, B35, B65, B103, and B104, previously reported to
      possess high affinity GABA binding, were analyzed for various cellular
      properties. They possessed peripheral but lacked central benzodiazepine binding.
      Only B65 cells possessed [3H-]muscimol binding; none bound [35S]TBPS. None of the
      cells exhibited GABA-stimulated chloride conductance with patch clamp recordings.
      By Western blots the cells possessed alpha subunits. Northern blot and polymerase
      chain reaction analysis showed that out of alpha 1, alpha 4, beta 1 and gamma 2
      subunits, only alpha 1 subunit mRNA was present. Thus, GABAA-receptor binding
      without associated central benzodiazepine receptor sites and without functional
      chloride channels appears to result from expression of an incomplete subunit
      composition.

PMID- 1379868
TI  - Failure of a protein synthesis inhibitor to modify glutamate receptor-mediated
      neurotoxicity in vivo.
AB  - The delayed neuronal death (DND) resulting from brief forebrain ischemia has
      recently been reported to be markedly attenuated by parenteral administration of
      the reversible protein synthesis inhibitor, anisomycin. Previous work suggests
      that ischemia-induced DND is mediated by glutamate acting at one or more
      glutamate receptors, since glutamate receptor antagonists have been reported to
      reduce ischemia-induced DND. Consequently, we tested whether anisomycin could
      modify DND induced by direct intracerebral administration of the excitotoxins, N
      methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxasole (AMPA) or
      kainic acid. Anisomycin, administered parenterally, in multiple doses did not
      alter DND induced by any of these excitotoxins, nor did combined parenteral and
      direct intracerebral injection of anisomycin protect against DND induced by AMPA.
      Thus, neurotoxicity induced by direct intracerebral administration of NMDA, AMPA
      or kainic acid does not appear to require de novo protein synthesis, and,
      therefore, is not likely to be mediated by the expression of a programmed cell
      death cascade.

PMID- 1379869
TI  - Patterns of glucose use after bicuculline-induced convulsions in relationship to
      gamma-aminobutyric acid and mu-opioid receptors in the ventral pallidum-
      functional markers for the ventral pallidum.
AB  - Bicuculline-induced convulsions increased glucose use throughout the brain and
      sharply demarcated the ventral pallidum and globus pallidus. Glucose use in the
      nucleus accumbens also increased after bicuculline-induced convulsions, except
      for a circumscribed region in the dorsomedial shell. Since the projection from
      the nucleus accumbens to the ventral pallidum contains gamma-aminobutyric acid
      (GABA) and the opioid peptide, enkephalin, the pattern of increased glucose use
      in the ventral pallidum and nucleus accumbens after bicuculline-induced
      convulsions was compared to the topography of GABAA and mu-opioid receptors. The
      pattern of glucose use in the nucleus accumbens and ventral pallidum resembled
      the topography of GABAA, but differed from that of mu-opioid receptors.
      Bicuculline may disinhibit GABAergic efferents to the ventral pallidum resulting
      in a dramatic increase in glucose use within striatopallidal synaptic terminals
      as well as in local terminals of the pallidal projection neurons.

PMID- 1379870
TI  - Imipramine inhibits intrathecal substance P-induced behavior and blocks spinal
      cord substance P receptors in mice.
AB  - The mechanism of the antinociceptive effect of the tricyclic antidepressant
      imipramine was investigated in mice. Intrathecal (i.t.) administration of
      imipramine produced dose-dependent antinociception in the tail-pinch and tail
      flick tests with ED50 values (95% confidence limit) of 27.5 (17.0-43.9) and 20.2
      (12.6-32.2) nmol, respectively. In substance P (SP)-induced nociceptive behavior,
      imipramine (i.t.) also produced dose-dependent antinociception with ED50 value of
      20.2 (16.1-25.2) nmol. Tissue concentration of imipramine was between 55.2 and
      104.4 nmol/g tissue when these ED50 values of imipramine were i.t. administered.
      In the SP-induced behavior, the antinociceptive effect of 31.6 nmol of imipramine
      was not antagonized by the alpha-adrenergic receptor antagonist phentolamine, the
      serotonergic receptor antagonist methysergide, or the opioid receptor antagonist
      naloxone. In vitro study, imipramine dose-dependently inhibited specific [3H]SP
      binding in the spinal cord homogenate with IC50 value of 2.37 x 10(-4) M and this
      value corresponds to 8.6 mumol/g tissue concentration. These data indicate that
      imipramine produces antinociceptive effect at about 100 times lower dose than SP
      receptor blockade.

PMID- 1379871
TI  - Enhanced release of immunoreactive CGRP and substance P from spinal dorsal horn
      slices occurs during carrageenan inflammation.
AB  - In vitro superfusion was used to examine the effect of inflammation on the
      release of immunoreactive calcitonin gene-related peptide (iCGRP) and substance
      P(iSP) from the dorsal horn of rats. Three hours after carrageenan, hindpaws
      exhibited hyperalgesia, edema, and hyperthermia. Spontaneous and capsaicin-evoked
      release of iCGRP and iSP were significantly increased following inflammation. The
      enhanced release of iCGRP and iSP in the dorsal horn may serve as a biochemical
      marker for the development of hyperalgesia.

PMID- 1379872
TI  - Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to
      acute clozapine in nucleus accumbens but not in caudate-putamen.
AB  - Clozapine alters mesolimbic dopamine (DA) function but spares nigrostriatal DA
      function in laboratory animals, but the underlying mechanism is unknown. In the
      present study, acute intraperitoneal injection of clozapine (5-40 mg/kg)
      increased extracellular DA levels in nucleus accumbens (Acb) and caudate-putamen
      (CPu) of awake, freely moving rats as measured by in vivo brain microdialysis,
      without anatomic selectivity. However, in serotonin (5HT)-denervated rats acute
      clozapine preferentially enhanced DA levels in Acb as compared to CPu. Since (i)
      up-regulation of 5HT receptors on DA neurons may result from 5HT denervation,
      (ii) clozapine has potent anti-5HT action, and (iii) 5HT receptors are more dense
      in Acb than CPu, these data appear to add additional weight to previous
      suggestions that a serotonergic mechanism may partly underlie clozapine's
      mesolimbic selectivity.

PMID- 1379873
TI  - Co-localized but target-unrelated expression of vasoactive intestinal polypeptide
      and galanin in rat dorsal root ganglion neurons after peripheral nerve crush
      injury.
AB  - Expression of vasoactive intestinal polypeptide (VIP) and galanin in dorsal root
      ganglion (DRG) neurons is known to be induced by peripheral nerve injury. We
      investigated (1) whether VIP and galanin were co-expressed by DRG neurons and (2)
      whether such neurons innervated specified peripheral targets (visceral, cutaneous
      or muscular). An antibody to the 200 kDa neurofilament subunit (NF200) was used
      as a marker for large type-A cells in the DRG. VIP and galanin were respectively
      observed in 22% and 67% of DRG neurons at the L5 spinal level after crushing of
      the sciatic nerve. Most VIP-containing neurons were small type-B cells (about
      90%) and approximately 95% of VIP-containing neurons also showed galanin-like
      immunoreactivity. Galanin was expressed by both large type-A and small type-B
      cells. Immunocytochemistry combined with a retrograde tracer revealed that about
      70-80% of the small type-B cells in each sensory division displayed VIP-like
      immunoreactivity, and that most of the tracer-labeled neurons also expressed
      galanin. These findings suggest that the expression VIP and/or galanin in
      response to peripheral nerve crush injury is a property common to visceral,
      cutaneous and muscular sensory neurons.

PMID- 1379874
TI  - Mesencephalic type I astrocytes mediate the survival of substantia nigra
      dopaminergic neurons in culture.
AB  - We previously demonstrated that substantia nigra (SN) support cells selectively
      increase SN dopamine (DA) neuron survival in dissociated primary culture.
      Increased survival was elicited specifically by nigral support cells; glia from
      other brain regions exerted lesser effects. We now report that Type I astrocytes,
      the principal component of SN support cell monolayers, mediate the enhanced DA
      cell survival. Initially, the predominant glial subtypes in SN support cell
      cultures were identified. Postnatal day 1 rat SN was dissociated and cells were
      grown to confluence (7-9 days in vitro; DIV). Monolayers were immunostained with
      antibodies against glial fibrillary acidic protein (GFAP; an astrocyte-specific
      marker), myelin basic protein (MBP; an oligodendrocyte marker), or A2B5
      (recognizes 0-2A progenitors and Type II astrocytes). The number of GFAP+ cells
      far exceeded MBP+ and A2B5+ cells, suggesting that astrocytes constituted the
      predominant subpopulation. Further, direct comparison of GFAP+ (Type I and Type
      II astrocytes) and A2B5+ (Type II astrocytes) cells indicated that the vast
      majority were Type I astrocytes. Greater than 98% of cells reacted with glial
      antibodies. To definitively characterize the cellular subtype that augments
      survival of DA neurons, glial subcultures were established. At 2 DIV, enriched
      populations of Type I or Type II astrocytes, or oligodendrocytes, were tested for
      the ability to elicit DA neuron survival. Embryonic day 16 rat SN dissociates
      were added and DA cell number was assessed with antibody against tyrosine
      hydroxylase (TH), the DA biosynthetic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379875
TI  - Galanin in the medial septal area impairs working memory.
AB  - Galanin, a peptide of 29 amino acids, is co-localized with acetylcholine in a
      subpopulation of neurons of the medial septal area (MSA) that project to the
      hippocampus. Galanin reverses the actions of acetylcholine in several biochemical
      and behavioral procedures, and may be involved in memory processes. To test the
      possibility that galanin acts on the cell bodies of MSA neurons, two measures of
      septohippocampal function were assessed following intra-septal microinfusion of
      galanin or two synthetic fragments of galanin (1-16 and 21-29). The behavioral
      measure was choice accuracy in a working memory task in a T-maze. The
      electrophysiological measure was hippocampal theta activity recorded from the
      dentate hilus. The galanin fragment, 1-16, and the complete peptide, 1-29,
      decreased choice accuracy and decreased hippocampal theta activity in a dose
      dependent fashion. Saline and the 21-29 fragment had no effect on choice accuracy
      and hippocampal theta. Sensorimotor performance was unaffected. These findings
      demonstrate that galanin impairs working memory when administered directly into
      the MSA and suggest that galanin inhibits MSA neural activity.

PMID- 1379876
TI  - Enhanced growth-dependent expression of TGF beta 1 and hsp70 genes in aortic
      smooth muscle cells from spontaneously hypertensive rats.
AB  - Enhanced proliferation of vascular smooth muscle cells (VSMC) from spontaneously
      hypertensive rats (SHR) as compared with Wistar-Kyoto rats (WKY) persists in long
      term culture and is characterized by an accelerated entry of these cells into the
      synthetic S phase of the cell cycle and a higher specific growth rate,
      particularly evident at high cell density. In the present study, we investigated
      by Northern blot experiments the expression of genes putatively involved in the
      regulation of VSMC growth. One of them is the transforming growth factor beta 1
      gene (TGF beta 1), a bifunctional modulator of cell growth whose action is
      dependent on cell density. The accumulation of TGF beta 1 mRNA was enhanced in
      growing SHR cells at every density studied as early as 24 h after inoculation
      with a further increase at later times. Protooncogenes c-fos and c-myc, which
      have been implicated in G1/S phase transition, have also been investigated in
      VSMC by Northern blot analysis. At low cell density, calf serum stimulated c-fos
      and c-myc mRNA expression was comparable in WKY and SHR cells whereas at high
      cell density, c-fos induction was higher in VSMC from SHR. SHR VSMC respond more
      to mitogenic stimulation and to environmental (e.g., heat) stress, particularly
      when growing near saturation density. hsp70 constitutes a gene family responsive
      to environmental stimuli (heat) and to mitogenic stimulation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1379877
TI  - Risperidone, a new antipsychotic with serotonin 5-HT2 and dopamine D2
      antagonistic properties.

PMID- 1379878
TI  - Psychobiology of violent behavior.

PMID- 1379879
TI  - Comparison of the actions of lithium, rubidium, and caesium on rat brain 5-HT
      function: pharmacological implications of ion channel function.

PMID- 1379880
TI  - The general anesthetic propofol: a biochemical tool to study the function of the
      GABA-coupled chloride channel.

PMID- 1379881
TI  - Hypothalamic neurochemical systems mediate drug effects on food intake.

PMID- 1379882
TI  - Risperidone in the treatment of chronic schizophrenic patients: an international
      double-blind parallel-group study versus haloperidol. The International
      Risperidone Research Group.

PMID- 1379883
TI  - Risperidone: clinical development: north American results.
AB  - This multicenter trial indicates that risperidone is an effective treatment for
      the positive and negative symptoms of schizophrenia. The most effective dose
      appears to be about 6 mg of risperidone daily. This dose was more effective than
      20 mg of haloperidol. In addition, this dose was associated with very low rates
      of extrapyramidal side effects.

PMID- 1379884
TI  - Influence of the culture medium on the synthesis of alpha-D-glucans by
      Streptococcus cricetus AHT.
AB  - Three different alpha-D-glucosyltransferases (GTFs) were separated from culture
      filtrates of Streptococcus cricetus strain AHT grown in a complex, standard
      medium in batch culture or under defined conditions of growth in the chemostat.
      Two of the enzymes (GTF-S1 and GTF-S2) converted sucrose into branched, soluble
      dextrans, and the third (GTF-I) produced a relatively linear, water-insoluble,
      predominantly (1----3)-linked alpha-D-glucan. When the organism was grown in
      complex medium modified by the removal of the fraction of high molecular weight,
      only GTF-S1 and GTF-S2 were released, and no GTF-I was detected. The water
      insoluble glucan fraction obtained by incubating the cell-free filtrate with
      sucrose contained from 17 to 25% of (1----3)-glucosidic linkages, and accounted
      for up to 78 and 4% of the total glucans derived from growth in standard and
      modified medium, respectively. The soluble glucans produced in the same reaction
      were fractionated with ethanol to give, from both media, two distinct dextrans
      comprising (1) a highly branched dextran similar to the S1-dextran product of GTF
      S1 and (2) a dextran containing fewer branch linkages and up to 86% of (1----6)
      alpha-D-glucosidic linkages. A GTF responsible for the synthesis of the latter
      dextran was not separated. The structures of the glucan fractions and the
      products of the separated GTF were examined by enzymic degradation and
      methylation analysis.

PMID- 1379886
TI  - A radioautographic study on RNA synthesis in aging mouse spleen after 3H-uridine
      labeling in vitro.
AB  - EM radioautographic study on RNA synthesis in aging mouse spleen was conducted
      after 3H-uridine labeling in vitro. The localization of radiolabelled precursor
      was used to determine the site of RNA synthesis. The site of the radiolabelled
      uridine uptake was localized in the haematopoietic cells, particularly in the
      lymphoblasts. In the labelled cells, most of the silver grains were localized in
      the nucleus, specifically in the euchromatin. Few cytoplasmic organelles such as
      the mitochondria and endoplasmic reticulum were labelled with 3H-uridine. Silver
      grains were also observed over the nucleoli. The labeling index was expressed as
      the percentage of labelled cells over the total number of cells counted. The
      labeling index increased from day one after birth and progressively until the
      14th day. Thereafter, the labeling index decreased gradually until the 10th
      month. A significant difference of p less than 0.05 was noted. In all the EMRAG
      analyzed, it was observed that the number of silver grains per cell increased
      proportionally with the labeling index. The result of the quantitation of the
      changes in RNA synthesis correlated well with the maturational development/aging
      of the animal.

PMID- 1379885
TI  - Action patterns of amylolytic enzymes as determined by the [1-14C]malto
      oligosaccharide mapping method.
AB  - A valuable technique for oligosaccharide mapping, utilizing radioactive malto
      oligosaccharides, multiple-ascent p.c., and radioautography, has been developed
      for identifying the action patterns of the glucoamylase isozymes, alpha-amylases,
      beta-amylase, glucosyltransferase, and glucanosyltransferase. The glucoamylase
      isozymes act by multi-chain mechanisms on malto-oligosaccharides and most likely
      on starch and glycogen. The alpha-amylases act endo-wise and randomly hydrolyze
      alpha-(1----4)- but not alpha-(1----6)-glucosidic bonds. These amylases may act
      by single-chain and/or multi-chain mechanisms, depending on the number of
      hydrolytic attacks per single encounter of the enzyme and the substrate. The beta
      amylases hydrolyze malto-oligosaccharides by a multi-chain mechanism. A fungal
      glucosyltransferase from Aspergillus niger transfers glucose units by a single
      chain mechanism from maltose to glucosyl acceptors to yield new gluco
      oligosaccharides with alpha-(1----4) and alpha-(1----6) linkages. A novel type of
      transferase isolated from Bacillus subtilis acts by a multi-chain mechanism and
      transfers segments of 2 to 5 glucose residues from malto-oligosaccharides to
      acceptor co-substrates. An alpha-amylase from the same organism removes
      maltotriose units from the non-reducing ends of oligosaccharides by a multi-chain
      mechanism.

PMID- 1379887
TI  - Inter-alpha-trypsin inhibitor-related immunoreactivity in human tissues and body
      fluids.
AB  - The distribution of inter-alpha-trypsin inhibitor (ITI) and related inhibitors
      was investigated in normal human tissues and body fluids by using an enzyme
      linked immunosorbent assay (ELISA) and a streptavidin-biotin-peroxidase
      immunohistochemical technique. ITI-related immunoreactivity was localized in
      different cell types of various organs, such as liver, kidney, testis, gross
      intestine, cutis and brain. Specific immunoreactivity was also detected in serum,
      urine and bronchial mucus. This widespread, but not ubiquitous pattern of
      localization suggests that, in addition to the well known plasmatic role, ITI
      and/or ITI-related inhibitors may play a number of different physiological roles
      in various human tissues.

PMID- 1379888
TI  - Alterations in cytokeratin expression precede histological changes in epithelia
      of vitamin A-deficient rats.
AB  - Normal epithelial cell differentiation is characterized by the production of
      distinct cytokeratin proteins. It is well known that epithelia of several organs
      show squamous metaplasia in a vitamin A-deficient status. It is not yet known
      whether these histological changes are concomitant with a change in cytokeratin
      expression. Therefore, 3-week-old female rats (BN/BiRij) were fed a vitamin A
      deficient diet for 8 weeks. The cytokeratin expression in epithelia of various
      organs was monitored immunohistochemically during the induction of vitamin A
      deficiency. Therefore, monoclonal antibodies specific for human cytokeratin 4, 5,
      5 + 8, 7, 10, 14, 18 and 19 were used. In a normal vitamin A status, the
      distributional pattern for the different cytokeratins in rats was similar to that
      reported for human tissue. No change in cytokeratin expression was seen in
      trachea, skin, liver and colon at any time point studied. Squamous metaplasia in
      urinary bladder and salivary glands was observed after six weeks on the vitamin A
      deficient diet. This was concomitant with a substitution of cytokeratins 4, 5 +
      8, 7, 18 and 19 by cytokeratin 10. The latter cytokeratin is specific for
      keratinized squamous epithelium. A change in cytokeratin expression was observed
      in bladder, ureter, kidney, salivary glands, uterus and conjunctiva before
      histological alterations appeared. In conclusion, the changes in cytokeratin
      expression observed under vitamin A deficiency in epithelia in vivo are in
      agreement with those described in other studies for epithelial cells in vitro.
      The changes in cytokeratin expression and the subsequent differentiation into
      squamous cells occurs in basal cells of the bladder but not in transitional
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379889
TI  - Role of vitronectin in embryonic rat endocardial cell migration in vitro.
AB  - Vitronectin is one of the extracellular matrices that mediate cell spreading and
      attachment in vitro. In the present paper, we demonstrate the involvement of
      vitronectin in the migration of cushion mesenchymal cells of the embryonic rat
      heart. Immunohistochemistry established the localization of vitronectin in the
      myocardial cells and in some of the cushion mesenchymal cells of the truncus
      arteriosus and atrioventricular canal. In vitro, vitronectin, fibronectin, and
      collagen type-I revealed significant stimulating activity for cushion mesenchymal
      cell migration. The distance migrated by cushion mesenchymal cells cultured on
      vitronectin, collagen type-I, or both vitronectin and fibronectin was similar,
      but that on fibronectin was significantly shorter. Following the addition of anti
      vitronectin IgG to the medium, the migration distance of cushion mesenchymal
      cells on fibronectin was remarkably increased. Most explants on vitronectin or on
      both vitronectin and fibronectin became detached from dishes after the addition
      of the antivitronectin antibody. Immunostaining revealed that cushion mesenchymal
      cells cultured on substrata other than vitronectin synthesized vitronectin. From
      these results, it is suggested that vitronectin is synthesized by myocardial
      cells and some cushion mesenchymal cells, and that vitronectin inhibits cell
      movement on fibronectin. This feature of vitronectin may be important in the
      regulation of the migration of cushion mesenchymal cell in vivo.

PMID- 1379890
TI  - [An immunohistochemical and ultrastructural study of 20 chordomas].
AB  - Altogether 20 chordomas were reported. The site distribution included 9 cases at
      the sacrococcygeal region, another 9 cases at the spheno-occipital region, 1 at
      the cervical vertebra, and another 1 at the lumbar vertebra. Histologic
      examination revealed that characteristic "physaliphorous cells" were easily
      identified in all the 19 cases. Tissue for immunohistochemistry study was
      available in 18 cases. Among them, tumor cells were found strongly positive to
      EMA, but negative for CEA. 16/18 cases also showed positive for keratin and S-100
      protein. Totally, 2 cases were studied ultrastructurally and there were abundant
      RER and microfilaments seen in the cytoplasm of the tumor cells but only few
      surface microvilli detected. The epithelial nature of chordoma is strongly
      supported by the ultrastructural and immunohistochemical findings of these 20
      cases.

PMID- 1379891
TI  - [Application of microwaves in special and immunohistochemical staining].
AB  - Special and immunohistochemical staining are commonly used in clinicopathological
      diagnosis. However, the processing of most staining methods takes quite a long
      time even to 1-2 days. Application of microwaves to the staining process such as
      for nerve myelin, striated muscle fibers, acid mucin, melanin, hemosederin,
      aspergillus, basement membrane, HHF-35, desmin, cytokeratin, etc. The results
      were satisfactory similar to those by the ordinary methods and the time required
      was greatly shortened. Besides, the titres of antibody required were also similar
      as those used for routine immunohistochemical technique. It is assumed that
      application of microwaves in staining process might be valuable for pathological
      diagnosis and particularly the efficiency could be greatly enhanced.

PMID- 1379892
TI  - Dissociation between contractile function and oxidative metabolism in
      postischemic myocardium. Attenuation by ruthenium red administered during
      reperfusion.
AB  - The oxidative metabolic rate may be disproportionately high compared with
      contractile function in postischemic reperfused myocardium. To study the
      potential involvement of intracellular calcium transport in high energy
      expenditure after reperfusion, we determined in isolated rat hearts the effect of
      ruthenium red, an inhibitor of mitochondrial calcium transport, on recovery of
      contractile function and oxidative metabolic rate. Hearts subjected to 60 minutes
      of no-flow ischemia exhibited, at 15 minutes after the onset of reperfusion, poor
      recovery of left ventricular pressure development to only 7% of the corresponding
      value measured in control hearts (p less than 0.01). However, myocardial oxygen
      consumption was recovered to 84% of control (p = NS). The ratio of isovolumic
      contractile performance (expressed as the product of heart rate and left
      ventricular pressure development) to myocardial oxygen consumption was severely
      depressed to 6% of control (p less than 0.01). Supplementation of the perfusate
      with 6 microM ruthenium red during the initial 40 minutes of reperfusion resulted
      in a reduction of myocardial oxygen consumption to 65% of the value measured
      after 15 minutes of reperfusion in hearts reperfused without ruthenium red (p
      less than 0.01), despite a threefold increase of left ventricular pressure
      development (p less than 0.05). Oxidation of both palmitate and glucose was
      reduced to a comparable extent by ruthenium red. The ratio of contractile
      performance to myocardial oxygen consumption increased progressively during
      infusion of ruthenium red and did not differ further from control hearts after 30
      minutes of reperfusion. Cumulative myocardial release of creatine kinase was
      reduced by 47% (p less than 0.05) in hearts reperfused with ruthenium red
      containing medium. The results provide circumstantial evidence for the hypothesis
      suggesting that enhanced energy expenditure by intracellular calcium transport
      may be involved in the mechanisms underlying the dissociation between left
      ventricular performance and myocardial oxidative metabolic rate early after
      postischemic reperfusion.

PMID- 1379893
TI  - Platelet-derived growth factor isoforms decrease insulin-like growth factor I
      gene expression in rat vascular smooth muscle cells and selectively stimulate the
      biosynthesis of insulin-like growth factor binding protein 4.
AB  - Platelet-derived growth factor (PDGF) is believed to be a critical mediator of
      vascular smooth muscle cell (SMC) proliferation. Because insulin-like growth
      factor (IGF) I (IGF-I) functions as a progression factor for the mitogenic
      effects of PDGF, we hypothesized that IGF-I gene expression and the production of
      IGF binding proteins (IGFBPs) by cultured rat aortic SMCs might be regulated by
      one or more of the three isoforms of PDGF: PDGF-AA, -BB, and -AB. IGF-I gene
      expression was highly dependent on cell density: IGF-I mRNA transcripts decreased
      markedly as a function of cell confluence. IGF-I mRNA content was inhibited to a
      similar degree by PDGF-AA, -BB, and -AB through a mechanism requiring protein
      synthesis. The inhibition was readily apparent at 4 hours, reaching approximately
      25% of control levels after 24 hours. Radioimmunoassayable IGF-I was only barely
      detectable in SMC-conditioned serum-free medium and not significantly modulated
      by PDGF. Western ligand blot revealed that vascular SMCs release 30-kd and 24-kd
      IGFBP into serum-free conditioned medium. PDGF isoforms did not significantly
      alter release of the 30-kd IGFBP but evoked a fivefold to sixfold increase in the
      24-kd IGFBP. The 24-kd IGFBP was found to comigrate with IGFBP-4, a recently
      identified binding protein that inhibits IGF action. The 30-kd protein was not
      merely a glycosylated form of IGFBP-4, because it was not sensitive to N
      glycanase digestion. PDGF-AA, -BB, and -AB markedly induced expression of IGFBP-4
      mRNA in a time- and concentration-dependent fashion. Vascular SMCs also express
      IGFBP-2 mRNA, but its abundance was not induced by PDGF. In conclusion, PDGF
      evokes a complex pattern of regulation of genes in the IGF/IGFBP system. By
      inhibiting IGF-I production and specifically inducing biosynthesis of the
      inhibitory binding protein IGFBP-4, PDGF may set in motion mechanisms to limit
      the final magnitude of the mitogenic response.

PMID- 1379894
TI  - Inhibition of nitric oxide synthase specifically enhances adrenergic
      vasoconstriction in rabbits.
AB  - 1. The effect of inhibition of nitric oxide biosynthesis using N-nitro-L-arginine
      (NOLA) was examined in conscious rabbits and rabbit isolated aortae. 2. In
      autonomically blocked conscious rabbits intravenous infusion of NOLA (15 mg/kg)
      significantly increased arterial pressure and hindlimb vascular resistance but
      did not affect heart rate. Depressor and hindlimb vasodilator responses to
      acetylcholine (3-12 micrograms/kg per min) were significantly attenuated in the
      presence of NOLA. In contrast, NOLA significantly enhanced responses to
      intravenous infusion of glyceryl trinitrate (10-40 micrograms/kg per min) in
      vivo. 3. Infusion of noradrenaline (1-4 micrograms/kg per min) or the release of
      neuronal noradrenaline in response to the infusion of tyramine (80-320
      micrograms/kg per min) increased arterial pressure and hindlimb vascular
      resistance in autonomically blocked conscious rabbits. After the administration
      of NOLA, the vasoconstrictor responses to both noradrenaline and tyramine were
      significantly enhanced. 4. In isolated rabbit aortae, NOLA (10 mumol/L)
      significantly impaired relaxant responses to acetylcholine but did not affect
      responses to glyceryl trinitrate. NOLA enhanced contractile responses to the
      adrenoceptor agonists noradrenaline and phenylephrine but did not affect the
      contractile responses to the thromboxane-mimetic U46619. 5. These data indicate
      that in autonomically blocked conscious rabbits, NOLA causes systemic
      vasoconstriction, impairs dilator responses to acetylcholine and enhances dilator
      responses to glyceryl trinitrate. In addition, NOLA enhances constrictor
      responses to both exogenous and neuronally-released noradrenaline. These results
      suggest that nitric oxide is important in the regulation of normal vascular tone
      and in the modulation of vascular responses to vasodilator and vasoconstrictor
      agents.

PMID- 1379895
TI  - In vitro transcription in isolated nucleoli of Tetrahymena pyriformis.
AB  - An in vitro transcription system was established using extrachromosomal nucleoli
      from Tetrahymena pyriformis macronuclei as a template. Ribosomal precursor RNA
      (pre-rRNA) and nascent pre-rRNA chains were removed from isolated nucleoli by
      treatment with RNase T1 and Sarkosyl. Nucleoli were then incubated in a RNA
      synthetic cocktail containing a cellular extract from Tetrahymena thermophila.
      The transcription product was examined for the presence of transcripts from T.
      pyriformis ribosomal DNA (rDNA) by P1 nuclease protection mapping using a DNA
      probe from a T. pyriformis rDNA clone. A sequence difference between T.
      pyriformis and T. thermophila in the 5' region of their 35S pre-rRNAs permitted
      exclusive detection of T. pyriformis transcripts. The results showed that
      faithful transcription initiation occurred in vitro from the in vivo initiation
      site of the nucleolar template and that the nucleolar template had a much higher
      efficiency of transcription than that of the purified rDNA clone. This system may
      offer unique advantages for future studies of transcriptional control during
      development and differentiation.

PMID- 1379896
TI  - Uridine uptake and RNA synthesis in the brain of torpid and awakened ground
      squirrels.
AB  - 1. Uptake of [3H]uridine into the nucleotide precursor pool after
      intraventricular injection occurs with the same intensity in the brain of torpid
      and normothermic awakened ground squirrels. This indicates that the membrane
      uridine transporters and uridine kinases operate in the hibernator's brain in a
      hypothermia-tolerant way. 2. Utilization of the [3H]uridine pool for synthesis of
      the rapidly labelled RNA in the brain of torpid ground squirrels falls more than
      eight times against RNA labelling in the brain of the active animals between
      bouts of hibernation. 3. Two hours from the beginning of the artificially
      provoked awakening, RNA uridine incorporation in the brain of ground squirrels
      has risen 6.5 times. 4. Drastic changes in [3H]uridine RNA labelling under the
      stable uridine uptake exclude the precursors and energy supply as the main
      factors determining changes in intensity of the brain RNA synthesis in the
      different stages of hibernation.

PMID- 1379897
TI  - Inhibition of RNA- and DNA-synthesis by citrinin and its effects on DNA precursor
      metabolism in V79-E cells.
AB  - 1. The RNA synthesis of V79-E cells was inhibited by the mycotoxin citrinin time-
      and concentration-dependently. 2. Among the different RNA species mainly the rRNA
      synthesis was found to be inhibited by 200 microM citrinin. 3. At different
      precursor concentrations DNA synthesis was inhibited by citrinin after 30 min at
      least whereas labelling of the acid soluble fractions was found to be 3-fold
      higher than in untreated cells. 4. Remarkable perturbation of the DNA precursor
      metabolism, including release of precursor into the medium, was found to occur
      during citrinin treatment.

PMID- 1379898
TI  - Identification and structural characterization of an LYT-2/3 homolog in
      tunicates.
AB  - 1. A serologic and structural homolog to murine Lyt-2/3 molecular complex was
      sought in tunicate hemocytes by using a monoclonal antibody specific to Lyt-2
      framework determinants (mAb 53-6.7). 2. This antibody labeled a distinct
      population of tunicate hemocytes, as determined in indirect immunofluorescence
      and FACS analysis, and immunoprecipitated disulfide-bonded subunits from
      hemocytes equivalent to the 38 kDa (alpha), 34 kDa (alpha') and 30 kDa (beta)
      subunits of murine Lyt-2/3 molecules. 3. As in mice, tunicate alpha- and alpha' 
      subunits each appeared to bear three N-linked oligosaccharides, one high mannose-
      and two complex-type glycans and focused as a number of heterogeneous spots on
      IEF gels. 4. In contrast, beta-subunits of both species were associated with a
      single N-linked glycan of the complex type and focused as basic components of
      limited charge heterogeneity. 5. Based on tryptic peptide patterns, alpha and
      alpha' -subunits, are likely to be structurally similar in both tunicate and
      mouse complexes. 6. However, CNBr cleavage patterns indicated that the alpha
      subunit of both species may differ in the size-location of the intrachain
      disulfide bridge. 7. Collectively our observations suggest the phylogenetic
      emergence of an Lyt-2/3 homolog at an early level of evolution.

PMID- 1379899
TI  - Lindane-induced changes in carbohydrate metabolism in Anguilla anguilla.
AB  - 1. Anguilla anguilla (L.) was exposed to a sublethal concentration of 0.167 ppm
      (0.25 of the 96-hr LC50) of lindane for 6, 12, 24, 48, 72 and 96 hr. 2. Changes
      in glycogen, glucose, pyruvate and lactate contents of liver and muscle after
      lindane exposure, were studied. 3. Muscle and liver glycogen levels decreased
      significantly during the exposure time. Muscle glucose values increased but on
      the other hand we found a decrease in those of liver. 4. Muscle and liver
      pyruvate content increased as did lactate levels in both tissues. 5. The observed
      effects of lindane on carbohydrate metabolism in fish are discussed in relation
      to acute stress syndrome.

PMID- 1379900
TI  - Substance P in the regulation of mucociliary transport in the frog palate.
AB  - 1. Mucociliary transport of carbon particles across the palate of anesthetized
      Rana pipiens was accelerated by electrical stimulation of the palatine nerve. 2.
      Transport was also accelerated by intracardiac injection of acetylcholine and of
      substance P in a dose-dependent manner. 3. Acceleration of transport by
      acetylcholine and by substance P was selectively blocked by atropine and by the
      substance P antagonist Spantide, respectively. 4. Acceleration of transport by
      nerve stimulation was blocked partially by atropine and by Spantide, and
      completely by the two administered concurrently. 5. It is concluded that nerve
      stimulation releases both acetylcholine and substance P or a similar
      neuropeptide. 6. Taken in conjunction with the literature, the data suggest that
      these substances are involved in the normal mechanism for stimulating mucociliary
      clearance of the palate in response to the presence of particles.

PMID- 1379901
TI  - Bactericidal action of a glycoprotein from the body surface mucus of giant
      African snail.
AB  - 1. Bactericidal action of a glycoprotein, Achacin, purified from the giant
      African snail, Achatina fulica Ferussac, has been studied. 2. Achacin kills both
      gram-positive and gram-negative bacteria, but only in their growing states. 3.
      Achacin does not have any bacteriolytic activity. 4. The strain which has no cell
      wall is a little more sensitive than the native strain and the cell membrane
      damaged strain. 5. Achacin was observed on the cytoplasmic membrane and on the
      cell wall of treated Escherichia coli by immunoelectron microscopy. 6. Achacin
      attacks the cytoplasmic membrane of the cell.

PMID- 1379902
TI  - Selection and identification of antigenic determinant of Mycobacterium
      tuberculosis H37Ra strain.
AB  - A new procedure for the selection of the antigenic determinant of Mycobacterium
      tuberculosis H37Ra strain is described. The bacterium components destroyed by
      ultrasonic were isolated by 15% SDS-PAGE, transferred onto nitrocellulose
      membrane, immunostained with McAbs against H37Ra. One McAb-positive fragment was
      obtained using the Western blot analysis. The molecular weight of the antigenic
      determinant is 35,000 dalton. The antigenic determinant is of immunological
      reactivity with McAb and TB patients' sera in dot-immunoassay and demonstrated in
      delayed skin tests in guinea pigs. The amino acid composition of the antigenic
      determinant was analysed. These suggest that the Western blot analysis may be a
      useful tool for the analysis of the antigenic determinant.

PMID- 1379903
TI  - [Rose bengal staining for clinical detection of oral premalignant lesions and
      carcinomas].

PMID- 1379905
TI  - Clinical evaluation of three anti-HCV ELISAs in patients with various liver
      diseases.
AB  - We measured antibodies to hepatitis C virus (HCV) in 380 patients with various
      liver diseases by three enzyme-linked immunosorbent assays (ELISAs): HCV antibody
      ELISA test (C100), KCL-163 (KCL) corresponding to the nonstructural protein of
      HCV, and JCC based on the translation product of the presumptive HCV core gene.
      Of 233 cases of non-A, non-B (NANB) liver disease, 63.9% were anti-C100 positive,
      69.1% were anti-KCL positive, and 79.8% were anti-JCC positive. Detection of
      serum HCV-RNA in 213 cases of chronic NANB liver disease revealed that the
      concordance was 80.3% for C100, 86.4% for KCL, 94.8% for JCC, and 95.3% for all
      three ELISAs. Overall, 85.4% of chronic NANB cases were considered to have type C
      disease with HCV infection. The most reliable assays for diagnosing chronic NANB
      liver disease as type C appeared to be the KCL and JCC ELISAs.

PMID- 1379904
TI  - Effect of replacement therapy with cholylsarcosine on fat malabsorption
      associated with severe bile acid malabsorption. Studies in dogs with ileal
      resection.
AB  - The efficacy of cholylsarcosine, a synthetic deconjugation-resistant and
      nonsecretory conjugated bile acid analog for the treatment of fat malabsorption
      caused by severe bile acid malabsorption, was assessed in an animal model. In two
      dogs, the ileum and ileocecal valve were resected, causing severe diarrhea,
      steatorrhea, bile acid malabsorption, and progressive weight loss.
      Cholylsarcosine was administered as the water-soluble sodium salt by mixing with
      the dog food. Various doses were explored as well as varying intakes of dog food.
      Fat absorption was assessed by gravimetric measurement of fecal fat; a
      nonabsorbable recovery marker (polyethylene glycol mol wt 4000) was used to
      correct for incomplete fecal collections. Cholylsarcosine caused a 5- to 30-fold
      increase in fat absorption but had no significant effect on weight loss or fecal
      weight. Duodenal content was collected during digestion of a meal via a
      surgically placed Thomas cannula; the aspirates were dilute, acidic, and had a
      low bile acid concentration. The bile acid concentration increased modestly when
      cholylsarcosine was administered, but remained below the critical micellization
      concentration. The results indicate that oral administration of cholylsarcosine
      improved dietary fat absorption in a canine model of severe bile acid
      malabsorption with associated steatorrhea and bile acid deficiency in the
      proximal small intestine. Studies with this compound in patients with nutritional
      problems because of steatorrhea and severe bile acid malabsorption appear
      warranted.

PMID- 1379906
TI  - Chemotherapy for Hodgkin's disease and aggressive non-Hodgkin's lymphoma. More is
      better, or is it?

PMID- 1379907
TI  - Clarithromycin. A review of its antimicrobial activity, pharmacokinetic
      properties and therapeutic potential.
AB  - Clarithromycin is an acid-stable orally administered macrolide antimicrobial
      drug, structurally related to erythromycin. It has a broad spectrum of
      antimicrobial activity, similar to that of erythromycin and inhibits a range of
      Gram-positive and Gram-negative organisms, atypical pathogens and some anaerobes.
      Significantly, clarithromycin demonstrates greater in vitro activity than
      erythromycin against certain pathogens including Bacteroides melaninogenicus,
      Chlamydia pneumoniae, Chlamydia trachomatis, Mycobacterium chelonae subspecies-
      chelonae and--abscessus, Mycobacterium leprae, Mycobacterium marinum,
      Mycobacterium avium complex, Legionella spp. and, when combined with its 14
      hydroxy metabolite, against Haemophilus influenzae. However, bacterial strains
      resistant to erythromycin are also generally resistant to clarithromycin. The
      antimicrobial activity of clarithromycin appears to be enhanced by the formation
      in vivo of the microbiologically active 14-hydroxy metabolite. In combination,
      additive or synergistic activity against a variety of pathogens including
      Haemophilus influenzae, Moraxella catarrhalis, Legionella species (principally
      Legionella pneumophila) and various staphylococci and streptococci has been
      demonstrated. Clarithromycin has a superior pharmacokinetic profile to that of
      erythromycin, allowing the benefits of twice daily administration with the
      potential for increased compliance among outpatients where a more frequent
      regimen for erythromycin might otherwise be indicated. The clinical efficacy of
      clarithromycin has been confirmed in the treatment of infections of the lower and
      upper respiratory tracts (including those associated with atypical pathogens),
      skin/soft tissues, and in paediatrics. Clarithromycin was as effective as
      erythromycin and other appropriate drugs including beta-lactams (penicillins and
      cephalosporins) in some of the above infections. A most promising indication for
      clarithromycin appears to be in the treatment of immunocompromised patients
      infected with M. avium complex, M. chelonae sp. and Toxoplasma sp. Small initial
      trials in this setting reveal clarithromycin alone or in combination with other
      antimicrobials to be effective in the eradication or amelioration of these
      infections. Noncomparative studies have provided preliminary evidence for the
      effectiveness of clarithromycin in the treatment of infections of the urogenital
      tract, oromaxillofacial and ophthalmic areas. However, the promising in vitro and
      preliminary in vivo activity of clarithromycin against Mycobacterium leprae and
      Helicobacter pylori warrant further clinical trials to assess its efficacy in
      patients with these infections. Despite the improved pharmacokinetic profile and
      in vitro antimicrobial activity of clarithromycin over erythromycin, comparative
      studies of patients with community-acquired infections reveal the 2 drugs to be
      of equivalent efficacy. However, clarithromycin demonstrates greater
      tolerability, principally by inducing fewer gastrointestinal
      disturbances.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1379908
TI  - Pharmacotherapy of childhood asthma. An inflammatory disease.
AB  - The recognition that asthma constitutes 2 kinds of physiopathological reactions,
      namely bronchospasms (immediate reactions) and inflammatory responses (late
      reactions), suggests that the treatment should be focused against these events.
      Furthermore, the allergen provocation model, showing the existence of immediate
      and late asthmatic reactions, can be used to study the effects of different
      antiasthmatic drugs. Recently, the importance of inflammation in the pathogenesis
      of asthma in adults has led to the development of therapeutic regimens in which
      anti-inflammatory treatments are used frequently as a first-line step in the
      management of asthma. Although at the moment the hard data showing inflammation
      in childhood asthma are scarce, it is assumed that childhood asthma constitutes
      the same kind of chronic inflammatory processes as in adult asthma and that its
      treatment should also include anti-inflammatory drugs.

PMID- 1379909
TI  - Drug therapy for nocturnal enuresis. Current treatment recommendations.
AB  - It is estimated that enuresis occurs in 5 to 7 million children in the United
      States. The treatment approach for enuresis is controversial, in large part due
      to a lack of consensus as to the exact cause of enuresis. Several factors either
      alone or together may contribute to this syndrome. In addition, there is strong
      evidence of a genetic component to enuresis. Pharmacotherapy continues to be the
      preferred treatment for both physicians and families. The most widely used drugs
      include antidepressants, anticholinergics, and desmopressin. The tricyclic
      antidepressant imipramine has been used extensively since the 1960s. The exact
      mechanism of action in enuresis is unknown although it appears to be related to
      the anticholinergic and antispasmodic effects of the drug. The most common
      adverse effects reported with imipramine include personality changes, insomnia,
      anorexia and anxiety. There has been renewed interest in antidiuretic treatment
      of enuresis. Researchers have found that enuretic children do not have the
      ability to reduce urine volume at night or concentrate the urine they produce
      during the night. Clinical trials with desmopressin administered by nasal
      inhalation report a marked reduction in enuretic episodes. Adverse effects were
      limited to nasal complaints, rhinitis, or epistaxis. Additional long term studies
      are needed to delineate desmopressin's role in therapy. Although the number of
      options for treatment of enuresis is expanding, criteria to predict patient
      response need to be defined.

PMID- 1379910
TI  - Management of gastroenteritis in early childhood.
AB  - The most important aspect of modern management of acute diarrhoeal illness in
      children is that of oral rehydration therapy, and drug therapy is very rarely
      indicated. Despite the dramatic decline in mortality and morbidity in recent
      years, there is still the need for continuing education in the appropriate use of
      oral rehydration solutions. The constitution of oral rehydration solutions and
      policies of feeding practices during illness continue to be controversial, mainly
      because of wide variation in the aetiology of the diarrhoea, the nutrition of the
      child, and the economic and public health factors involved in any particular
      community. The priority of all healthcare workers is to provide simple guidelines
      in the use of a safe oral rehydration solution while discouraging unsafe
      treatments.

PMID- 1379911
TI  - Topical corticosteroids. Which drug and when?
AB  - A number of factors have to be taken into account when dealing with the treatment
      of skin diseases with topical corticosteroids, including disease type and phase,
      potency of the drug, safety, site to be treated, age of the patient, and drug
      formulation. Concerning the specific indications for topical corticosteroid
      treatment, we can distinguish skin diseases in which: (a) topical corticosteroids
      are the treatment of choice; (b) topical corticosteroids are useful as
      alternative and/or adjuvant treatment; (c) the proposed use of topical
      corticosteroids has to be confirmed as useful; and (d) topical corticosteroids
      can be used as a symptomatic treatment. Within these groups, the treatment
      schedule has to be adjusted according to the above mentioned general factors.

PMID- 1379912
TI  - Alglucerase. A review of its therapeutic use in Gaucher's disease.
AB  - Alglucerase is a mannose-terminated form of human placental glucocerebrosidase,
      developed to treat patients with Gaucher's disease. Functional glucocerebrosidase
      is deficient in Gaucher's disease, an autosomal recessive lipid storage disorder
      that affects people of all ethnic backgrounds, but has a higher incidence among
      East European Jews (Ashkenazim). Gaucher's disease manifests with
      hepatosplenomegaly, bleeding disorders and bone disease, with the more rare
      subtypes (types 2 and 3) featuring neurological dysfunction. Prior to the
      development of enzyme replacement therapy, treatment for Gaucher's disease was
      mainly symptomatic relief. Primary treatment with glucocerebrosidase focuses on
      removal of the lipid metabolite that causes the pathology. Because of the rarity
      of Gaucher's disease clinical trials are small, and much of the data
      investigating alglucerase therapy have been obtained from studies of patients
      with type 1 disease, the prevalent subtype. Nonetheless, after intravenous
      administration of alglucerase, improvements are evident within 6 months of
      therapy. Patients have increased haemoglobin levels and platelet counts, and
      decreased incidences of epistaxis and bruising. Spleen and liver size are
      reduced, and skeletal parameters improve. Children gain height and most patients
      receiving alglucerase therapy are able to resume work and daily activities.
      Alglucerase is well tolerated, with few mild adverse reactions reported. Although
      the pharmacokinetic and pharmacodynamic information for alglucerase is limited,
      its unequivocal efficacy justifies enzyme replacement therapy with this compound
      as first-line treatment for patients with Gaucher's disease, for whom treatment
      options are limited.

PMID- 1379915
TI  - The components of merocyanine-540 absorption spectra in aqueous, micellar and
      bilayer environments.
AB  - Spectral-data-processing and curve-fitting techniques have been applied to the
      decomposition of merocyanine-540 absorption spectra in aqueous, micellar and
      bilayer environments. The various resolved component bands have been assigned to
      dye monomers, dimers, or larger aggregates, either in polar or non-polar
      environments. The analysis of spectral parameters (lambda max and integrated
      intensity) of the overall spectra and of each component has revealed that
      merocyanine 540 is a useful probe in studies of membrane structure and dynamics
      using visible-absorption spectroscopy. In particular, the monomer lambda max and
      the integrated intensity, i.e. area, of the dimer population are very useful in
      this respect. The monomer lambda max is especially sensitive to polarity changes
      and is thus useful, e.g. in the precise determination of critical micellar
      concentrations. The fractional area of the dimer increases with the packing
      density of the phospholipid-hydrocarbon region near the interface and is thus
      very sensitive to changes in vesicle curvature and to the presence of sterols or
      intrinsic polypeptides in the bilayer.

PMID- 1379916
TI  - Intranuclear compartmentalization of transcribed and nontranscribed c-myc
      sequences in Namalva-S cells.
AB  - This investigation is centered on the intranuclear localization of transcribed
      and nontranscribed c-myc sequences in human Namalva-S cells bearing t(8;14)
      translocation. Southern hybridization showed that the breakpoint in the truncated
      allele of c-myc lies outside the characteristic 12.8-kbp EcoRI fragment: as
      Northern analysis indicated, this reorganization induces a high level of c-myc
      transcription. Following high-salt treatment, EcoRI digestion and centrifugation,
      isolated nuclei from the same cells are separated into two residual fractions: a
      heavier P fraction including nuclear matrix structures and a light S fraction
      representing dehistonized chromatin fibres. Comparative hybridization experiments
      revealed that the above procedure separates the c-myc sequences between the two
      fractions. To locate the site of intranuclear c-myc transcription, we performed
      run-on experiments with two fractions, topologically analogous to the residual P
      and S fractions but maintaining the original chromatin organization. These
      experiments indicated that chromatin P fraction harbours actively transcribed c
      myc sequences while chromatin S harbours nontranscribed ones. Further experiments
      have clarified that the transcribed c-myc sequences are firmly bound to the
      matrix by multiple attachment sites, arranged throughout the entire gene locus.
      It was found, moreover, that at the site of attachment the interaction between
      DNA and the matrix components is realized via proteins. Controls with the beta
      globin gene, which is constitutively nonexpressed in Namalva-S cells but upon
      induction is highly expressed in murine erythroleukemia cells, completely
      confirmed the conclusion we had made for the intranuclear localization of c-myc.
      Thus the experiments presented here support the more common idea that the
      transcribed and nontranscribed sequences are precisely compartmentalized.

PMID- 1379914
TI  - Didanosine. A review of its antiviral activity, pharmacokinetic properties and
      therapeutic potential in human immunodeficiency virus infection.
AB  - Didanosine is a dideoxynucleoside analogue which undergoes intracellular
      conversion to the putative active triphosphate metabolite. The active metabolite
      appears to inhibit viral reverse transcriptase and terminate the proviral DNA,
      and produces virustatic inhibition of actively replicating human immunodeficiency
      virus (HIV) at clinically relevant concentrations. In phase I studies didanosine
      had beneficial effects on various surrogate markers of clinical efficacy and also
      improved clinical manifestations of HIV infection, with a 21-month survival rate
      of 80% in patients with acquired immune deficiency syndrome (AIDS) and 93% in
      patients with AIDS-related complex (ARC) in 1 study. Didanosine also improved
      CD4+ cell counts in a phase II/III trial in patients previously treated with
      zidovudine, whereas cell counts declined in patients continuing zidovudine
      therapy. However, the effects of didanosine on clinical end-points (disease
      progression, survival, HIV encephalopathy) remain to be established. Peripheral
      neuropathy and pancreatitis are the predominant dose-limiting adverse events and
      didanosine therapy should be withdrawn in patients developing signs or symptoms
      of pancreatitis and during acute treatment of Pneumocystis carinii pneumonia.
      However, at currently recommended clinical dosages didanosine is generally well
      tolerated with minimal haematological toxicity. Thus, in a therapeutic area with
      few treatment options, didanosine offers a welcome alternative for patients
      intolerant of, or resistant to, zidovudine. There are a number of clinical trials
      in progress evaluating didanosine alone or in combination with other antiviral
      agents, and these results are awaited with considerable interest.

PMID- 1379917
TI  - Precise epitope mapping of monoclonal antibodies to the cytoplasmic side of the
      acetylcholine receptor alpha subunit. Dissecting a potentially myasthenogenic
      epitope.
AB  - The epitopes for twelve monoclonal antibodies against the cytoplasmic side of the
      acetylcholine receptor (AChR) alpha subunit were precisely mapped using over 300
      continuously overlapping synthetic peptides attached on poly(ethylene) rods. mAb
      cross-reactive between Torpedo and human AChR generally bound to the homologous
      peptides from both species. Epitopes 4-10-residues long were identified. One mAb
      could bind to either arm on both sides of a beta-turn structure. Five mAb bound
      to a very-immunogenic cytoplasmic epitope on alpha 373-380 (VICE-alpha). Three of
      the mAb against VICE-alpha were earlier found to cross-react with non-AChR
      protein(s), present in thymomas from myasthenia gravis patients but absent in
      thymomas from non-myasthenics. Since VICE-alpha has a potentially crucial
      pathogenic role, the antigenic role of each residue within it was subsequently
      studied by 55 analogues, most having single amino acid substitutions. All the mAb
      against VICE-alpha bound similarly but not identically to the analogues, thus
      explaining their known binding heterogeneity. Lys373 proved indispensable for mAb
      binding. Ile376, Glu377, Gly378 and Lys380 were quite critical, while Ser374,
      Ala375 and Val379 seemed rather inactive. These data should prove instructive in
      searches for VICE-alpha-like epitopes carrying autoantigens with potential
      involvement in myasthenia gravis and should further expand the applications of
      the anti-(AChR) mAb in AChR studies.

PMID- 1379918
TI  - Dignity of the perinatal optimality score of Prechtl.

PMID- 1379919
TI  - Bioavailability of oral isbufylline in rabbits.
AB  - The bioavailability of isbufylline was assessed in male rabbits given 12 mg/kg
      i.v. (intravenous) or per os (oral) according to a randomized design. The
      concentrations of unbound (fu = 54.0) isbufylline were considered in plasma as a
      function of time, after i.v. and oral administration. After oral administration
      in saline solution, a mean absolute oral bioavailability of 59.6% was calculated.
      The drug is rapidly absorbed and the comparison of the kinetic profiles after
      i.v. and per os administration, revealed a rapid elimination: t1/2 27.3 and 28.8
      min respectively, and a total body clearance of 67.06 ml/min/kg. Urinary recovery
      0-48 h accounted for less than 1% of the dose.

PMID- 1379920
TI  - No evidence for the existence of preformed antibodies against hydroxyethyl starch
      in man.
AB  - Using the highly sensitive ELISA technique for detecting anti-hydroxyethyl starch
      (HES) antibodies in man sera from 1,056 patients were analyzed. Patients of both
      sex, who had never had any prior contact with HES, were included in the study. In
      none of the cases could any titer of HES-reactive antibodies be detected. These
      data suggest that in man preformed HES-reactive antibodies do not exist or are
      extremely rare. In any case, unlike dextran-reactive antibodies, they should not
      have a high clinical importance. The mechanism behind the very rarely observed
      anaphylactoid reactions after HES application is still unknown.

PMID- 1379921
TI  - Efficacy of terazosin in patients with benign prostatic hyperplasia.
AB  - Terazosin, a selective, long-acting alpha 1-adrenergic blocker, was evaluated in
      44 men with benign prostatic hyperplasia. The dose was titrated from 2 to 20 mg
      nightly depending on improvement in symptoms and flow rate. All men completed at
      least 3 months of therapy, 26 had 6 months and 19 received 9-12 months of
      terazosin. There was an average increase of 2 ml/s in the peak urinary flow rate
      compared to baseline. This was statistically significant at the 3-month level.
      Residual urine decreased under treatment at each 3-month time interval. Prior to
      initiation of terazosin the mean was 165 ml, and it was 62, 100, and 41 ml at 3,
      6 and 9 months respectively. There was a statistically significant improvement in
      both the obstructive and irritative symptom scores. Side effects were minimal;
      only 1 patient discontinued terazosin due to a hypotensive episode. Terazosin was
      found to be safe and effective in the dose range of 2-20 mg taken at bedtime in
      men with symptoms related to benign prostatic hyperplasia. The present study did
      not identify any baseline parameters such as initial prostate volume, peak flow
      rates, or obstructive or irritative symptom scores that correlated with clinical
      outcome.

PMID- 1379922
TI  - Nucleolar organizer regions in prostatic adenocarcinomas. Comparison with flow
      cytometric analysis, tumor grade, stage and serum prostate-specific antigen
      levels.
AB  - Twenty-eight cases of prostatic adenocarcinomas have been selected and the mean
      argyrophil nucleolar organizer region (AgNOR) count for each case was evaluated.
      Nine of these tumors were of high, 13 of median and 6 of low differentiation. It
      was found that as the tumors became less differentiated, the AgNOR count
      increased (p less than 0.001). Stage of the disease, serum prostate-specific
      antigen (PSA) value, and DNA ploidy of all these cases have been examined as well
      but no statistically significant correlation among these three parameters and the
      AgNOR count was found.

PMID- 1379924
TI  - First Canadian clinical study of transurethral hyperthermia in benign prostatic
      hyperplasia. Assessment of 220 patients.
AB  - Since August 1990, we used the Thermex-II system to treat prostatism in 220
      patients for whom an indication of transurethral prostatectomy was proposed, in
      85% by some other urologists and the last 15% by us. The treatment was offered on
      a clinical research basis, and the patient received large information. No
      complications other than 10 short-term retentions (2-15 days), mild hematuria and
      2 marked prostatic edema were noted. Objective amelioration was seen in 78%, and
      subjective amelioration was noted in 83%. Only 6 patients needed surgery.

PMID- 1379913
TI  - Systemically administered antifungal agents. A review of their clinical
      pharmacology and therapeutic applications.
AB  - Systemic antifungal agents express great diversity in their pharmacokinetic
      profiles, mechanisms of action, and toxicities. Understanding the diverse
      pharmacokinetic properties of systemic antifungals is critical to their
      appropriate application. Amphotericin B, drug of choice for most invasive
      mycoses, has unique pharmacokinetic properties, binding initially to serum
      lipoproteins and redistributing from blood to tissues. Dosing recommendations are
      based on the specific infection and the status of the host. Lipid formulations of
      amphotericin B may be able to attenuate some of its toxicities. Flucytosine is a
      water-soluble, fluorinated pyrimidine that possesses excellent bioavailability.
      It is administered only in combination with amphotericin B because of frequent
      development of secondary drug resistance, and is associated with dose-dependent
      bone marrow suppression. The antifungal azoles are relatively well tolerated,
      have broad spectrum antifungal activity, and are fungistatic in vitro.
      Ketoconazole and itraconazole are highly bound to plasma proteins, are
      extensively metabolised by the liver, and are relatively insoluble in aqueous
      solution. By comparison, fluconazole is only weakly bound to serum proteins, is
      relatively stable to metabolic conversion, and is water soluble. Fluconazole
      penetrates the cerebrospinal fluid well and is approved for primary and
      suppressive therapy of cryptococcal meningitis in AIDS patients. The
      echinocandins have a narrow spectrum of antifungal activity, being effective only
      against Candida spp.

PMID- 1379923
TI  - A cytologic, ultrastructural and immunocytochemical comparison of tumor cells and
      cell cultures originating in invasive bladder carcinoma.
AB  - Tumor cells and urine-voided cells from patients with invasive bladder carcinoma
      as well as from healthy patients were examined cytologically, ultrastructurally
      and immunocytochemically. The ultrastructure of tumor cells showed an abundant,
      dilated, rough endoplasmic reticulum in the form of membrane-bound vacuoles full
      of granular to fibrillar material located perinuclearly and/or paranuclearly.
      Some cells exhibited enlarged modified lysosomes containing sparce flocculent and
      particulate precipitate. Papanicolaou staining of these cells showed two
      basophilic cytoplasmic textures, one green glossy-patchy, perinuclearly and/or
      paranuclearly, well segregated from the other texture of peripheral
      hematoxylinophilic foamy cytoplasm, comparable to the cytologic features of cell
      cultures originating in invasive bladder carcinoma. PAS diastase showed double
      distribution and texture of the perinuclear glycosaminoglycans, a glossy
      accumulated mass and large granules. Glycosaminoglycan sacs similar to those of
      cell cultures were also present in tumor-dispersed cells. There was a nonspecific
      binding of antisera against lysozyme, human chorionic gonadotropin and alpha 1
      trypsin in normal and tumor cells. Tumor cells and tissues were positive for
      alpha 1-chymotrypsin distributed perinuclearly and in large spheres. Normal cells
      lacked the above characteristics. The results indicate that it is feasible to use
      the aforementioned characteristics in conjunction with the existing bladder
      cytologic criteria for malignancy as markers in urothelial cancer with regard to
      prognosis of superficial tumors with high malignant potential.

PMID- 1379925
TI  - Preliminary results of transurethral microwave thermotherapy in the treatment of
      benign prostatic hyperplasia in Turkey.
AB  - This prospective study was conducted in order to evaluate the efficacy of
      transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic
      hyperplasia (BPH). A single TUMT session of 55 min was delivered as an ambulatory
      procedure without anesthesia to 180 patients. 20 (69%) of the 29 patients who
      were catheterized due to urinary retention prior to the treatment were able to
      urinate freely after the treatment. In 91 patients with a follow-up of 3 months,
      the mean maximum flow rate (MFR) was 7.9 ml/s prior to the treatment and 12.1
      ml/s after the treatment (p less than 0.02). The mean residual urine after
      voiding (PVR) of these patients was 104 and 54 ml before and after TUMT,
      respectively (p = 0.0001). The mean Madsen symptom score (SS) was 14 before and
      7.5 after the treatment (p = 0.0001). The patients with pretreatment MFR higher
      than 7.0 ml/s, PVR less than 150 ml and SS lower than 15 benefited better from
      TUMT. As the findings indicated, TUMT is an alternative treatment modality in BPH
      in selected cases, although the number and the follow-up of our series are
      insufficient to draw a precise conclusion yet.

PMID- 1379926
TI  - Effect of digital rectal examination on serum concentration of prostate-specific
      antigen.
AB  - Prostate-specific antigen (PSA) is used for screening and follow-up of patients
      with prostate cancer. The effect of certain diagnostic procedures on PSA serum
      levels is not well defined. Therefore, the effect of digital rectal examination
      (DRE) on PSA serum levels was investigated. No significant difference was
      observed in PSA values before and after DRE when blood samples were taken 1-3 min
      after palpation of the prostate. Kinetic studies demonstrated a significant
      increase in PSA values up to the factor 3.2 in 14 of 19 patients 2-6 h after DRE.
      In 9 of 14 cases, PSA was within the initial range 24 h after DRE. That means
      that a urologist is allowed to take blood samples for the determination of PSA at
      least within 3 min after palpating a suspicious prostate without getting false
      positive results.

PMID- 1379927
TI  - Half-life of prostate-specific antigen after radical prostatectomy: the decisive
      predictor of curative treatment?
AB  - Prostate-specific antigen (PSA) half-life calculated in 51 patients subsequent to
      radical prostatectomy was found to identify patients with residual disease
      earlier and more reliably than the criterion of not achieving undetectable PSA
      levels postoperatively. It is proposed that residual tumor affects the half-life
      by contributing to the serum level of PSA. When PSA half-life was calculated
      solely in potentially cured patients, we found a half-life of 1.5 days being
      considerably shorter than in the previous reports based on patient populations
      regardless of the outcome of disease in the follow-up.

PMID- 1379929
TI  - Neurokinin agonists differentially affect A9 and A10 dopamine cells in the rat.
AB  - The effect of selective neurokinin (NK) receptor agonists on the activity of A9
      and A10 dopamine cells was assessed using extracellular recording. A higher
      proportion of A10 cells which were administered the NK1 receptor agonist GR73632
      or the NK3 receptor agonist senktide showed an effect, whereas the NK2 receptor
      agonist GR64349 did not discriminate as clearly between the two cell groups. The
      most frequently encountered response in all cases was an increase in firing rate.

PMID- 1379928
TI  - Blockade of thromboxane/endoperoxide receptor-mediated responses in the pulmonary
      vascular bed of the cat by sulotroban.
AB  - The effects of sulotroban (BM13.177; SK & F 95587), a thromboxane (TX)
      A2/endoperoxide (PGH2) receptor blocking agent on responses to the TXA2/PGH2
      mimics, U46619 and U44069, were investigated in the pulmonary vascular bed of the
      intact-chest cat under constant flow conditions. Injections of U46619 and U44069
      directly into the perfused lobar artery caused dose-related increases in lobar
      arterial pressure without altering left atrial pressure. Following administration
      of sulotroban in a dose of 5 mg/kg i.v., dose-response curves for U46619 and
      U44069 were shifted to the right in a parallel manner. The duration of the
      blocking effect of sulotroban was investigated, and responses to U46619 returned
      to approximately 50% of control in 120 min and were not significantly different
      from control 240 min after administration of the receptor antagonist. Sulotroban
      was without significant effect on responses to prostaglandin (PG) D2 or F2 alpha
      or serotonin, histamine, norepinephrine, angiotensin II or BAY K8644, an agent
      which enhances calcium entry. Sulotroban was without effect on responses to
      endothelin (ET)-1, sarafotoxin (S) 6a or S6c and platelet-activating factor
      (PAF). Sulotroban did not alter baseline vascular pressures in the cat and
      responses to the PG and TXA2/PGH2 precursor, arachidonic acid, were reduced. The
      present data show that sulotroban selectively blocks TXA2/PGH2 receptor-mediated
      responses in a competitive and reversible manner in the pulmonary vascular
      bed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379930
TI  - Galanin inhibits sexual behavior in male rats.
AB  - Intracerebroventricular injection of galanin potently inhibited (0.5
      micrograms/rat) or completely suppressed (5.0 micrograms/rat) copulatory activity
      in sexually experienced male rats, without producing any other obvious behavioral
      deficit. It is suggested that galanin, known to potently stimulate feeding
      behavior, may be involved in the inverse modulation of feeding and sexual
      behaviors.

PMID- 1379931
TI  - Specific binding sites for 125I-endothelin-1 in the porcine and human spinal
      cord.
AB  - Specific binding sites for 125I-endothelin-1 (125I-ET-1) in the spinal cord were
      investigated using quantitative receptor autoradiographic and chemical cross
      linking methods. The binding sites were highly concentrated in porcine and human
      spinal cord areas corresponding anatomically to the dorsal horn (Rexed's laminae
      I-III), an area around the central canal (lamina X) and the principal part of the
      intermediolateral nucleus (IMLp). The localization of the binding sites differed
      from those of 125I-omega-conotoxin GVIA (125I-CgTx) and 125I-Bolton-Hunter
      substance P (125I-BH-SP), with the exception that the IMLp shared 125I-ET-1 with
      125I-CgTx and 125I-BH-SP binding sites. Specific 125I-ET-1 binding sites in the
      areas examined were characteristically single and of high affinity. There were no
      differences between the potencies of unlabeled ET family peptides, ET-1, ET-2, ET
      3 and sarafotoxin S6b at inhibiting 125I-ET-1 binding to the areas. Chemical
      cross-linking studies showed that 125I-ET-1 and 125I-ET-3 mainly bound to a
      protein with molecular mass of 43 kDa in the porcine and human thoracic spinal
      cord membranes. The present finding shows the neuronal significance of this newly
      discovered peptide in the spinal cord.

PMID- 1379932
TI  - Activation of T84 cell chloride channels by carbachol involves a phosphoinositide
      coupled muscarinic M3 receptor.
AB  - Muscarinic agonists stimulate Cl- secretion across monolayers of the colon tumor
      epithelial cell line, T84. The muscarinic receptor has been characterized in T84
      cell homogenates by radioligand binding using [3H]N-methylscopolamine ([3H]NMS).
      [3H]NMS bound to a single population of sites at 25 degrees C in 100 mM NaCl, 20
      mM HEPES, 10 mM MgCl2, pH 7.4 buffer, with calculated Kd = 278 (+/- 44) pM and
      Bmax = 40 (+/- 6) fmol/mg protein (n = 4). Binding was reversible (diss. t1/2 =
      18 +/- 3 min) and stereoselective (dexetimide Ki = 0.3 nM) much greater than
      levetimide (Ki = 8300 nM). Antagonists exhibited the following rank order of
      potencies and Ki values (nM): atropine (0.54) greater than 4-diphenylacetoxy-N
      methylpiperidine methobromide (4-DAMP) (0.84) greater than dicyclomine (14) =
      hexahydrosiladifenidol (18) greater than pirenzepine (136) greater than AF-DX 116
      (3610). The same sequence was observed for inhibition of carbachol-induced 125I
      efflux from T84 monolayers. This is indicative of an M3 'glandular' muscarinic
      receptor. Coupling to second messenger systems was examined by labelling
      monolayers with [14C]arachidonic acid (AA) or [3H]inositol. Carbachol (0.3 mM)
      did not release [14C]AA from labelled lipids, but ionomycin produced a dose
      dependent increase in media [14C]AA. Carbachol (0.3 mM) elevated inositol
      monophosphate 14-fold. The results suggest that muscarinic agonists stimulate Cl-
      secretion by interacting with an M3 receptor coupled to inositide lipid
      hydrolysis.

PMID- 1379933
TI  - Influence of oligopeptide aldehydes on intracellular Ca2+ concentration in rat
      pituitary cells.
AB  - We investigated the effects of some synthetic tripeptide aldehydes, earlier shown
      to influence pituitary hormone secretion and 45Ca2+ uptake, on the intracellular
      free Ca2+ concentration ([Ca2+]i) of rat anterior pituitary cells in suspension.
      Boc-D-Phe-Leu-Phenylalaninal or Boc-D-Phe-Leu-Prolinal in the tested range of 1
      100 or 200 microM, respectively, were ineffective in influencing basal [Ca2+]i
      but caused a concentration-dependent inhibition in K+ (25 mM)-induced [Ca2+]i
      elevation. The IC50 of both effects was about 50 microM. In contrast, they did
      not interfere with the stimulation caused by the calcium channel agonist BAY K
      8644 and were also ineffective in influencing the receptor-mediated stimulus of
      thyrotropin-releasing hormone on [Ca2+]i. On the basis of the present and
      foregoing results the possible involvement of calcium channels is discussed, but
      different mechanisms mediating the tripeptide aldehyde inhibition are also
      considered. A third tripeptide aldehyde, Boc-Gln-Leu-Lysinal (Boc-GLL), showed
      ionophore-like properties. This nontoxic substance caused a dose-dependent rise
      up to 400% (at 100 microM) in [Ca2+]i. Its effect is not mediated by voltage
      dependent calcium channels, as it cannot be inhibited either by the classical
      calcium channel antagonists verapamil and nifedipine, or by the above-mentioned
      inhibitory tripeptide aldehydes. When we decreased the extracellular Ca2+
      concentration by the addition of 4 mM EGTA, the effect was inverted and Boc-GLL
      caused a large fall in [Ca2+]i. We suggest that Boc-GLL may open cell membrane
      pores through which Ca2+ moves along the concentration gradient.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1379934
TI  - Ribosomal RNA gene restriction patterns of Helicobacter pylori: analysis and
      appraisal of Hae III digests as a molecular typing system.
AB  - Ribosomal RNA gene restriction patterns (ribopatterns) of 162 strains of
      Helicobacter pylori from 93 patients were studied to assess their suitability for
      use as the basis of a molecular typing system. Computer-assisted numerical
      analysis of Hae III ribopatterns of 122 strains from 9 countries in 4 continents
      showed that almost every strain had a distinct and unique ribopattern and only
      strains from the same individual were genomically matched in all bands or with
      minor (1-2 band) differences. Hae III ribopatterns offered high typability and
      reproducibility but were too discriminatory for large-scale epidemiological
      typing purposes because no rational basis for grouping strains was evident. In
      contrast, composite band profiles based on 21 band loci within the Hae III
      ribopatterns, which were used to compare strain sets selected on toxigenicity and
      geographical origin, were more conserved. Minor differences between some strain
      sets in several band loci were detected but generally the composite profiles were
      a reproducible feature of H. pylori. We conclude that Hae III ribopatterns
      provide an excellent fingerprint for small-scale studies of genomic variation in
      defined populations, such as sequential patient isolates, but are too specific
      for general typing of H. pylori.

PMID- 1379935
TI  - Characterization of enterococcal isolates by restriction enzyme analysis of
      genomic DNA.
AB  - A restriction enzyme analysis (REA) of chromosomal DNA for the intra-species
      characterization of enterococci is reported. The DNA was extracted by a rapid
      method and digested with the restriction enzyme Sal I to provide a characteristic
      'fingerprint' consisting of 10-20 bands in the 1.6-5.0 kb range. One hundred and
      eighty enterococcal isolates were examined; 5 were type strains, 15 from an out
      patient clinic and 160 from a geographically isolated British Antarctic Survey
      Base. The epidemiologically unrelated out-patient clinic isolates gave readily
      distinguishable patterns, whereas isolates from the geographically isolated
      community showed evidence of colonization. This technique provided a highly
      discriminatory method of isolate characterization for Enterococcus faecalis, E.
      faecium and E. durans suitable for epidemiological studies. A sample of isolates
      were probed with 16 + 23 S ribosomal RNA from Escherichia coli. Discrimination
      between isolates was poorer than with REA, although good correlation was observed
      between the results of the two techniques.

PMID- 1379936
TI  - Neuronal loss or replacement in the injured adult cerebral neocortex induces
      extensive remodeling of intrinsic and afferent neural systems.
AB  - The question of how the cerebral cortex responds over time to changes in cortical
      neuronal number was addressed by inducing excitotoxic cortical neuronal loss,
      either alone or followed by homotypic fetal cortical cell suspension grafts, in
      adult rats. Following neuronal cell loss, rapid gliosis and inflammation
      temporarily maintained tissue volume. As gliosis subsided, tissue shrinkage
      occurred until the ratio of glia to neurons approached that of normal neocortex.
      After neuronal loss, total cortical glutamate uptake and glutamic acid
      decarboxylase activity dropped markedly and remained low, and there was a gradual
      but considerable reduction in the total size of afferent fiber networks. However,
      when expressed as concentrations per unit of tissue or protein, histological and
      neurochemical cortical markers showed increases during the phase of tissue
      shrinkage and in the long-term equilibrated to near normal levels. Retrograde
      tracing studies showed that the reduction in total afferent fiber network is
      accompanied by the atrophy of afferent neuronal cell bodies. Grafts of fetal
      cortical cells placed after excitotoxic lesions provided long-term reconstitution
      of cortical tissue mass, maintained afferent fiber systems, and prevented both
      the atrophy and surrounding cellular gliosis of some afferent neuronal cell
      bodies for over a year, but were unable to innervate the main cortical target
      regions in the host. Thus after neuronal loss or replacement, the adult cerebral
      neocortex and its afferent systems remodel to a density of neurons, glia, and
      afferent fibers similar to that found in intact tissue, illustrating structural
      plasticity toward a dynamic equilibrium.

PMID- 1379937
TI  - 8-Chloro-cyclic adenosine monophosphate, a novel cyclic AMP analog that inhibits
      human glioma cell growth in concentrations that do not induce differentiation.
AB  - Cyclic AMP is supposed to play a role in cell growth and differentiation via
      activation of protein kinase A. The cAMP signal transduction pathway may
      therefore be used as a target for the development of anticancer drugs. We
      compared the effects of 8ClcAMP, a newly developed cAMP analog, to the effects of
      more commonly used cAMP analogs on the morphology and the proliferation of three
      human glioma cell lines. 8ClcAMP was the most potent growth inhibitor, exhibiting
      an IC50 of approximately 10 microM and inducing growth arrest in all three glioma
      cell lines at a concentration of 100 microM. The cAMP analogs 8CPTcAMP, dibutyryl
      cAMP, and 8BrcAMP were much less potent. If used in concentrations that induce
      growth arrest, both 8CPTcAMP and IBMX, but not 8ClcAMP, induced morphological
      differentiation of the glioma cells. Apparently, the growth-inhibiting effect of
      8ClcAMP is not paralleled by its ability to induce morphological differentiation.
      The explanation for this phenomenon may be that 8ClcAMP does not exert its growth
      inhibiting effect via activation of cAMP-dependent protein kinase. Two
      alternative mechanisms of action are discussed. Since 100 microM 8ClcAMP retarded
      the growth of normal rat astrocytes only to a marginal extent, without cytotoxic
      effects, it is concluded that 8ClcAMP may offer interesting perspectives in the
      treatment of malignant glioma.

PMID- 1379938
TI  - Neutrophil kinetics shortly after initial administration of recombinant human
      granulocyte colony-stimulating factor: neutrophil alkaline phosphatase activity
      as an endogenous marker.
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was
      administered (1.5 micrograms/kg body weight) subcutaneously once daily for 5 to 9
      days to 5 patients with malignant lymphoma. In all patients, initial
      administration of rhG-CSF induced a rapid fall in the neutrophil count within 30
      minutes, followed by a recovery and an increase in the neutrophil count within
      150 min. A rapid fall in the neutrophil count was accompanied by increased
      expression of neutrophil C3bi-receptors, and neutrophils left in the circulation
      had lower activity of neutrophil alkaline phosphatase (NAP) and phagocytosis. A
      decrease in the NAP scores observed at 30 min reflected a preferential decrease
      of neutrophils with high NAP activity. A recovery and an increase in the
      neutrophil count were accompanied by a further decrease of NAP scores, which was
      caused by a preferential increase of neutrophils with lower NAP activity. The NAP
      scores of mature neutrophils from peripheral blood were not affected by in vitro
      treatment of cells with rhG-CSF for up to 150 min at 37 degrees C. These findings
      and the previous observations that neutrophils in the circulating and marginal
      pools have high NAP activity and neutrophils in the bone marrow pool have low NAP
      activity taken together suggest that, following initial administration of rhG
      CSF, functionally active neutrophils leave the bloodstream preferentially, which
      is primarily followed by an influx of neutrophils from the bone marrow, but not
      by demargination of sequestered neutrophils.

PMID- 1379939
TI  - Modification of human long-term bone marrow cultures: establishment of a
      functional stromal microenvironment devoid of myeloid progenitors.
AB  - Differences in the plastic adhesive properties of bone marrow (BM) cells were
      used to initiate modified stromal layers (MSL) from long-term cultures by
      removing non-adherent cells shortly (4 to 18 hours) after initial seeding.
      Following this early modification, adherent cells generated a confluent layer
      after 21 days of culture. Cellular characteristics of volume and spontaneous
      fluorescence determined by flow cytometry showed that the MSL included 82%
      fibroblastic stromal cells, 8% macrophages and 10% myelomonocytic cells.
      Furthermore, clonogenic assays revealed that the MSL were devoid of hematopoietic
      progenitor cells. MSL were found to sustain long-term myelopoiesis for at least 7
      weeks from exogenously added hematopoietic progenitors isolated from bone marrow
      (CD34+ cells), thereby demonstrating their functionality. The present
      experimental model appears of interest for the study of interactions between
      defined populations of hematopoietic cells and cells of the adherent layer. Of
      importance, our present modifications of human long-term bone marrow culture are
      technically simple and do not involve manipulation of the stromal cells.

PMID- 1379940
TI  - Iron content in human alveolar macrophages.
AB  - Intracellular iron can be estimated semi-quantitatively by histochemical
      determination using the ferrocyanide reagent's score. Particle-induced X-ray
      emission (PIXE) allows accurate determination of various elements including iron
      in cells and biological fluids. Both techniques have been used to measure iron in
      alveolar macrophages gathered by bronchoalveolar lavage. The purpose of this
      study was to investigate the clinical usefulness of the PIXE technique in
      occupational respiratory medicine and in various pulmonary diseases. Using the
      PIXE method, we measured the iron content of alveolar macrophages in healthy
      subjects, with and without occupational exposure to iron dust, and in patients
      with pulmonary diseases (chronic obstructive pulmonary disease (COPD), lung
      cancer, Goodpasture's syndrome). Our results were then compared with those
      obtained with the ferrocyanide reagent. Intramacrophagic iron was 0.33 +/- 0.21
      micrograms.10(-6) (mean +/- SD) cells in healthy non-smoking subjects without
      occupational exposure. Intramacrophagic iron was increased in smokers, iron
      steelworkers, and in patients with COPD or lung cancer even in the absence of
      pulmonary haemorrhage. The two patients with Goodpasture's syndrome had high
      intramacrophagic iron content. About 80% of the whole bronchoalveolar lavage
      fluid iron content was in the cells. Mean iron content of blood monocytes,
      lymphocytes and neutrophils of eight healthy subjects was significantly lower
      than that of alveolar macrophages. A significant correlation was found between
      iron determination by the PIXE method and the ferrocyanide reagent's score (r =
      0.89). We conclude that intramacrophagic iron may be increased in steelworkers
      and subjects with pulmonary haemorrhage, but also in asymptomatic smokers, in
      COPD and lung cancer patients without occupational exposure to iron dust.

PMID- 1379941
TI  - Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion
      molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic
      subjects.
AB  - Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T
      lymphocytes in allergic inflammation in asthma. There is evidence suggesting that
      the expression of adhesion molecules on endothelial cells and of their receptors
      on leucocytes is involved in this process. To investigate these mechanisms we
      have obtained bronchial mucosal biopsies from 10 normal subjects and from 10
      symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6
      weeks of inhaled beclomethasone dipropionate (BDP) during which time their
      clinical response was monitored. Frozen sections were stained by the
      immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify
      expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for
      endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were
      also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic
      protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic
      but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both
      the epithelium and endothelium and ELAM-1 in endothelium, with no significant
      differences being apparent between the asthmatic and normal subjects. Topical BDP
      markedly reduced the mucosal eosinophilia without affecting the expression of
      either adhesion molecule. Using this method, we conclude that there is basal
      expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not
      significantly different from that in asthmatics, and that it is insensitive to
      suppression with corticosteroids at an inhaled dose that causes clinical
      improvement.

PMID- 1379942
TI  - Folylpolyglutamate analogs can inhibit casein kinase II from Xenopus laevis.
AB  - Polyglutamate analogs of folate and related compounds were tested as inhibitors
      of casein kinase II (CK II) obtained from Xenopus laevis. The inhibitory capacity
      of the pteroyl, 4-amino-10-methyl pteroyl (the methotrexate aromatic moiety), and
      p-aminobenzoil derivatives increased as the number of gamma-glutamates attached
      went from 2 to 7. The nature of the aromatic head, group was also important since
      hexa-gamma-glutamatic acid had no inhibitory activity while the
      folylhexaglutamate derivatives were strong inhibitors with relative potency of
      methotrexate greater than pteroyl greater than p-aminobenzoic acid. The
      inhibition of CK II by methotrexate gamma-pentaglutamate was competitive with
      casein and showed an apparent K(i) of 90 microM.

PMID- 1379943
TI  - The compact state of reduced bovine pancreatic trypsin inhibitor is not the
      compact molten globule.
AB  - Reduced bovine pancreatic trypsin inhibitor (BPTI) has been shown to be in a
      compact state [(1988) Biochemistry 27, 8889-8893]. This leads to the proposal
      that this compact state may be a compact molten globule folding intermediate.
      Optical rotatory dispersion in the visible region failed to show the presence of
      pronounced secondary structures in the reduced BPTI and no binding of 8-anilino-1
      naphthalenesulphonic acid to reduced BPTI could be detected. Yet, no cooperative
      thermal transition was detected by tyrosine fluorescence. These experiments show
      that reduced BPTI is not in the compact molten globule state.

PMID- 1379944
TI  - Modulation of expression of multidrug resistance gene (mdr-1) by adriamycin.
AB  - The acquired resistance to various drugs in cancer is mediated by P-glycoprotein
      (P-gp) which is encoded by the mdr-1 gene. An increased level of mdr-1/P-gp was
      demonstrated after chemotherapy administered to treat cancer in humans. To
      clarify the direct effect of anticancer drugs on mdr-1/P-gp expression, we
      investigated the change in transport of adriamycin (ADR), and the expression of
      the mdr-1 gene and P-gp in an ADR-treated, multidrug-resistant leukemic cell line
      (K562/ADR500). The addition of ADR induced the over-expression of mdr-1/P-gp,
      which led to a transient decrease in the intracellular accumulation of ADR
      although the difference was not statistically significant. A maximal effect was
      observed after 4 h incubation, returning to the baseline level after further
      incubation for 12-24 h. The phosphorylation of P-gp was inversely correlated with
      the levels of P-gp. These observations suggest that ADR itself modulates both the
      expression and function of P-gp. Determination of the optimal schedule for
      administering adriamycin is essential to achieving the optimal effect in treating
      cancer.

PMID- 1379945
TI  - Biological characteristics of the Calliphora vomitoria agglutinin.
AB  - The galactose specific agglutinin from Calliphora vomitoria was found to be
      expressed in the haemolymph of all the larval instars, but could not be detected
      at any other time during the life cycle. The haemagglutinating activity was
      insensitive to wounding of the tegument or injection of saline; however, a
      significant increase in haemagglutinating titre could be induced upon inoculation
      of the haemocoel with biotic or abiotic particulate material. The agglutinin also
      actively agglutinated several bacterial species and appeared capable of playing a
      role in particle--haemocyte interaction. The presence of the purified agglutinin
      significantly increased the attachment of fetuin-derivatized beads to haemocytes
      in vitro, and this activity could be specifically reduced by the addition of
      galactose, suggesting that the agglutinin may act as an opsonin.

PMID- 1379946
TI  - Influence of chemotherapy on hormone receptor concentration in a xenotransplanted
      endometrial cancer.
AB  - There is growing evidence that chemotherapy may influence the hormone receptor
      capacity in human carcinomas. The consideration of this assumption may be of
      importance for the therapeutic management of tumors with metastatic spread which
      underwent previous adjuvant chemotherapy. Therefore we investigated the influence
      of six different kinds of chemotherapy on the hormone receptor concentration and
      the percentage of receptor positive cells in xenotransplanted endometrial cancer.
      Our results can be summarized as follows: (1) We find neither a significant
      decrease in hormone receptor capacity after chemotherapeutic treatment
      (biochemical determination), nor do we see a decrease in the percentage of ER/PR
      pos. cells (immunohistochemistry). (2) On the other hand, there is no increase in
      hormone receptor concentration inducible by chemotherapy and no increase in ER/PR
      pos. cells immunohistochemically.

PMID- 1379947
TI  - Annual meeting of the American Academy for Cerebral Palsy and Developmental
      Medicine. 1992. Abstracts.

PMID- 1379950
TI  - Functional changes of the exocrine perfused rat pancreas in cerulein-induced
      pancreatitis.
AB  - Functional changes of the exocrine pancreas in cerulein-induced pancreatitis were
      evaluated with the isolated perfused rat pancreas. In control specimens (n = 7),
      baseline pancreatic juice volume was 0.23 +/- 0.06 microliter/min and after
      stimulation with CCK-8 (10(-10) M) and secretin (10(-10) M), it was 2.26 +/- 0.45
      microliter/min, and in cerulein-induced pancreatitis specimens (n = 8), the
      corresponding values were 0.11 +/- 0.03 and 0.23 +/- 0.08 microliter/min. The
      amylase content in the pancreatic juice (IU/min) was 0.73 +/- 0.15 (baseline) and
      7.03 +/- 1.66 (stimulated) in the control specimens, and 0.012 +/- 0.002
      (baseline) 0.018 +/- 0.004 (stimulated), in the cerulein-induced pancreatitis
      specimens. Amylase and lipase concentrations in the portal effluents were
      significantly higher in the cerulein-induced pancreatitis (481.3 +/- 79.4 IU/ml,
      283.7 +/- 47.2 BALB U/ml) than in the control specimens (10.7 +/- 1.8 IU/ml, 8.9
      +/- 2.9 BALB U/ml). Using the electron microscope fusion of large vacuoles with
      lateral plasma membrane was observed in cerulein-induced pancreatitis. In
      cerulein-induced pancreatitis, normal secretion was markedly decreased, and the
      lateral secretion was suggested to result in the elevation of pancreatic enzyme
      levels in portal effluents.

PMID- 1379948
TI  - Hepatitis-C-virus-related chronic liver disease of sporadic type: clinical,
      serological and histological features.
AB  - Hepatitis C virus (HCV) is the most important cause of transfusion-related non-A,
      non-B hepatitis. It is also thought to be the prime cause of non-transfusion
      related or sporadic chronic liver disease. To assess the extent of HCV infection
      and its significance in this last form, we evaluated the clinical, serological
      and histological features of 84 consecutive HCV-related patients without a
      history of blood or blood products transfusion, alcohol or intravenous drug abuse
      or other known risk factors. Our results indicate that 68 patients (81%) had
      signs of chronicity, and 33 (39.2%) had superimposed cirrhosis. Serum abnormal
      alanine aminotransferase and gamma-glutamyltransferase activities represented
      good predictive markers of liver histological signs of chronicity. The levels of
      serum gammaglobulins were found to parallel histological severity of liver
      disease. One or more hepatitis B virus (HBV)-associated markers were present in
      52 patients (61.9%). Only 6 (7.1%) were chronic HBV carriers, and 3 of them had
      signs of active virus replication. These data indicate that HCV plays a major
      role in the etiology of sporadic chronic liver disease. Its presence is
      associated with histological forms of chronic liver disease in most patients, who
      likely represent chronic HCV carriers.

PMID- 1379949
TI  - Sensitization against pancreatic antigen in Sjogren's syndrome and chronic
      pancreatitis. Preliminary communication.
AB  - A fractionated pancreatic antigen was prepared using a monoclonal antibody, SP3
      1, which reacts with the duct cells of various exocrine organs. The cell-mediated
      immune response to this antigen was studied by the leukocyte migration inhibition
      test (LMT) in patients with chronic pancreatitis (CP), Sjogren's syndrome (SjS),
      and chronic sialoadenitis (CSA). The migration index (MI) for the LMT was 0.97 +/
      0.07 in normal controls (mean +/- SD, n = 11, range: 0.88-1.08). A positive LMT
      result (MI less than 0.82 = mean -2 SD in controls) was obtained in 7/8 (88%) SjS
      patients, 4/22 (18%) CP patients, 2/3 CP patients with SjS, and 0/3 CSA patients.
      These results indicated sensitization against the pancreatic antigen in most SjS
      patients and some CP patients, and may suggest that an immune response to a
      common antigenic determinant of the duct cells of exocrine glands plays a role in
      the pathophysiology of both diseases.

PMID- 1379952
TI  - Sequential induction of syndecan, tenascin and cell proliferation associated with
      mesenchymal cell condensation during early tooth development.
AB  - The cell surface proteoglycan, syndecan, and the extracellular matrix
      glycoprotein, tenascin, are expressed in the mesenchyme during early development
      of many organs. We have studied the expression patterns of syndecan and tenascin
      during initiation of tooth development and in association with mesenchymal cell
      condensation and compared these with cell proliferation. Syndecan, tenascin and
      bromodeoxyuridine (BrdU) incorporation were localized by triple-labelling
      immunohistochemistry in serial sections of molar tooth germs of mouse embryos.
      Prior to formation of the epithelial tooth bud, syndecan accumulated in the
      mesenchymal cells which underlie the presumptive dental epithelium, but tenascin
      was not detected at this stage. Tenascin appeared during initiation of the
      epithelial down-growth at the lingual aspect of the tooth germ. During subsequent
      formation of the epithelial bud, at the late bud stage, syndecan and tenascin
      became exactly colocalized in the condensed mesenchyme which was clearly
      demarcated from other jaw mesenchyme. The expression of syndecan and tenascin was
      accompanied by rapid cell proliferation as indicated by marked BrdU
      incorporation. When development advanced to the cap stage, syndecan staining
      intensity in the dental papilla mesenchyme increased further whereas tenascin
      became reduced. In conclusion, the results demonstrate that the expression
      patterns of syndecan and tenascin overlap transiently during the period of
      mesenchymal cell condensation and that this is accompanied by cell proliferation.
      Syndecan and tenascin may play a role in growth control and in
      compartmentalization of the dental mesenchymal cells in the condensate.

PMID- 1379951
TI  - The effects of retinoic acid on the expression of alpha-fetoprotein and albumin
      genes in rat hepatoma cell lines.
AB  - Many transcriptional regulators can stimulate or repress gene expression
      depending on the cellular or genetic contexts. Thus dexamethasone increases the
      amount of alpha-fetoprotein mRNA in Morris rat hepatoma derived cell line McA-RH
      8994 cells, but decreases it in McA-RH 7777 cells. In the present study, we
      demonstrated that retinoic acid, whose receptors belong to the steroid/thyroid
      hormone receptor gene family, also enhanced the expression of alpha-fetoprotein
      and albumin gene in McA-RH 8994 cells, but had no effect on alpha-fetoprotein
      gene expression in McA-RH 7777 cells. In contrast to the effect of dexamethasone
      on the alpha-fetoprotein gene expression, which requires ongoing protein
      synthesis, cycloheximide, a protein synthesis inhibitor, enhanced the effect of
      retinoic acid. Actinomycin D inhibited the retinoic acid mediated increase in
      alpha-fetoprotein and albumin mRNA expression. Since the McA-RH 8994 cells did
      not express retinoic acid receptor beta mRNA, the observed regulatory effects of
      retinoic acid on alpha-fetoprotein and albumin gene expression were not mediated
      through retinoic acid receptor beta. We also conclude that the regulation was at
      the level of transcription and that retinoic acid and dexamethasone probably
      regulate the expression of liver specific genes through different mechanisms.

PMID- 1379953
TI  - The role of gastric secretagogues in regulating gastric histamine release in
      vivo.

PMID- 1379954
TI  - Inhibition of neuronally mediated secretion in rat colonic mucosa by
      prostaglandin D2.
AB  - The effect of prostaglandin D2 (PGD2) on ion transport across the mucosa of the
      descending colon was studied in rats. PGD2 dose-dependently decreased baseline
      short-circuit current of mucosa-submucosal preparations mounted either in the
      Ussing chamber or mounted as an everted sac. However, with the everted sac
      technique, the tissue was about 1000 times more sensitive to PGD2. Concomitant
      with the decrease in short-circuit current, PGD2 increased the mucosal-to-serosal
      fluxes of sodium and chloride and decreased the serosal-to-mucosal flux of
      chloride. PGD2 inhibited the secretory action of the PGI2 analogue iloprost, PGD2
      alpha, and neurotensin. The action of these secretagogues was dependent on the
      presence of the submucosal plexus. In contrast, PGD2 had no effect on the
      increase in short-circuit current caused by PGD2, substance P, or serotonin, the
      actions of which were not dependent on the presence of the submucosal plexus. The
      results indicate that the action site of the antisecretory mechanism of PGD2 is
      localized in the secretomotor neurons.

PMID- 1379956
TI  - Identification of motor neurons to the longitudinal muscle of the guinea pig
      ileum.
AB  - Motor neurons that innervate the longitudinal muscle of the guinea pig ileum were
      identified by retrograde transport from the longitudinal muscle plexus in
      organotypic culture. Motor neurons had short projections, less than 3.5 mm long,
      and never had Dogiel type II morphology; most labeled neurons had morphological
      characteristics of Dogiel type I neurons. Immunoreactivity for choline
      acetyltransferase was present in 97% of retrogradely labeled nerve cell bodies,
      reflecting the dominant cholinergic input to the longitudinal muscle layer.
      Substance P immunoreactivity was present in 48% of motor neurons, indicating that
      it or a similar tachykinin that mediates noncholinergic excitatory transmission
      is likely to be released by a subset of cholinergic motor neurons. This strongly
      suggests that the difference in frequency dependence of substance P and
      acetylcholine release is attributable to different release mechanisms rather than
      to activation of separate populations of motor neurons. Immunoreactivity for the
      calcium-binding protein calretinin was present in 87% of longitudinal muscle
      motor neurons. The neurochemical coding of longitudinal muscle motor neurons
      indicated that they constitute about one quarter of all myenteric neurons and are
      distinct from circular muscle motor neurons.

PMID- 1379955
TI  - Expression of vascular adhesion molecules in inflammatory bowel disease.
AB  - The expression of the vascular adhesion molecules ELAM-1 (endothelial leukocyte
      adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1) was evaluated
      in colonic mucosa of patients with inflammatory bowel disease and normal controls
      by immunocytochemistry. VCAM-1 was found to be constitutively expressed in
      lymphoid aggregates in normal colonic mucosa and was not significantly enhanced
      or altered in distribution in mucosa of patients with inflammatory bowel disease
      regardless of the activity of the inflammatory process. In contrast, ELAM-1 was
      not detected by these techniques in normal colonic mucosa (n = 11) or in colonic
      mucosa of patients with inflammatory bowel disease which was either uninvolved or
      quiescent (n = 30). However, high levels of ELAM-1 were consistently found on
      endothelial surfaces in association with active inflammation in affected areas of
      colonic mucosa in patients with either ulcerative colitis (n = 27) or Crohn's
      colitis (n = 9). In addition, ELAM-1 appeared to be present within neutrophils
      which had migrated into crypt abscesses in affected mucosa. Similar analysis was
      carried out in the cotton-top tamarin (CTT), a primate that experiences an
      idiopathic chronic diffuse colitis resembling human ulcerative colitis. Although
      anti-human VCAM-1 antibodies did not react with the CTT, anti-human ELAM-1
      stained endothelial surfaces in mucosal biopsies from CTT with active colitis. No
      ELAM-1 was identified in mucosa of CTT in which colitis activity was quiescent.
      Thus ELAM-1 is expressed on colonic endothelial surfaces in association with
      inflammation and may play an important role in facilitating leukocyte migration
      into sites of active IBD involvement.

PMID- 1379957
TI  - Somatostatin 28 and coupling of human interdigestive intestinal motility and
      pancreatic secretion.
AB  - To determine the effects of small increases in somatostatin 28 plasma
      concentrations on human interdigestive gastrointestinal motility and pancreatic
      secretion, six fasting volunteers were intubated with gastroduodenal multilumen
      tubes and motility and pancreatic enzyme secretion were measured. Subjects
      received intravenous NaCl and somatostatin 28 at 11 and 44 pmol.kg-1.h-1 for 120
      minutes or at least one interdigestive cycle. The two doses increased plasma
      somatostatin 28 levels within the physiological or into the supraphysiological
      range, respectively. Somatostatin 28 at 11 and 44 pmol.kg-1.h-1 decreased the
      length of the interdigestive motility cycle by 50% and 67% compared with
      controls, respectively (both P less than 0.002). Propagation velocity of the
      migrating motor complex (P less than 0.01) and plasma motilin were decreased (P
      less than 0.01). The smaller and larger dose decreased pancreatic enzyme outputs
      by 50% and 65%, respectively (P less than 0.005), but with the smaller dose,
      phase III-associated enzyme outputs were greater than phase I outputs. These
      findings suggest that small changes in somatostatin 28 plasma concentrations
      modulate human interdigestive motility and pancreatic enzyme output while
      coupling of motor and secretory events is preserved.

PMID- 1379958
TI  - [Therapy for symptomatic pain in advanced breast cancer].
AB  - From 1983-1989, 106 patients with breast cancer were treated in our pain
      management unit on 6767 treatment days. Pain was caused by bone metastasis in 73%
      of patients. Neuropathic pain was reported by 32% of the patients. In all but
      four of these patients, new tumour growth was diagnosed. Patients were treated
      according to WHO analgesic guidelines with non-opioids on 16% of the days, non
      opioids in combination with weak opioids on 36% and with strong opioids on 38%
      (orally 90%, parenterally 4% of the days). Due to the prevalence of bone pain non
      steroidal antiinflammatory drugs were given on 56% of the days. The high
      incidence of neuropathic pain led to frequent use of co-analgesics
      (antidepressants 17%, anticonvulsants 12%, steroids 12% of the days). Adjuvant
      therapy for symptoms other than pain was given on 86% of the days. Whilst 92% of
      patients reported more than moderate pain on admission, 45% obtained complete
      pain relief beginning from the first days of treatment. On 92% of the days,
      patients described their pain as moderate or less. Side effects were treated
      symptomatically and played a minor role in a reason to change therapy.

PMID- 1379959
TI  - Isolation and characterization of a lipopolysaccharide mutant of Legionella
      pneumophila.
AB  - A mutant unable to bind a monoclonal antibody (mAb 1E6) directed against
      serogroup 1 lipopolysaccharide (LPS) was isolated from L. pneumophila strain
      Philadelphia-1. SDS-PAGE analysis of isolated LPS from the mutant and wild type
      revealed that there were no obvious structural differences between the two LPS.
      The results from Western-blot experiments showed that the mutant LPS was unable
      to bind mAb 1E6 but retained the ability to bind polyclonal serogroup 1
      antibodies. Loss of the LPS epitope recognized by mAb 1E6 did not alter the
      ability of the mutant to multiply in human monocyte-like U937 cells. Also, the
      mutant, like wild type, was resistant to killing by normal human serum. These
      results show that a minor change in the antigenic composition of serogroup 1 LPS
      has no effect on the virulence properties of strain Philadelphia-1. Additionally,
      this mutant may be useful for molecular genetic analysis of serogroup 1 LPS
      biosynthesis and assembly.

PMID- 1379960
TI  - Light-activated adenyl cyclase from Trichoderma viride.
AB  - The effect of light on adenyl cyclase (E.C. 4.6.1.1) and 3':5'-cyclic-AMP
      phosphodiesterase (E.C. 3.1.4.17) activity of Trichoderma viride was
      investigated. Adenyl cyclase proved to be a membrane-associated enzyme, requiring
      Mn2+ and was activated by light. In contrast, 3':5'-cyclic-AMP-phosphodiesterase
      showed no light-stimulated activity. The activity of 3':5'-cyclic-AMP
      phosphodiesterase was present mainly in the cytosol and was stimulated by Mg2+.

PMID- 1379961
TI  - Bleomycin-ifosfamide-cis-platinum (BIP) in pelvic recurrence of previously
      irradiated cervical carcinoma: a second look.
AB  - The response rate and survival obtained with the combined regimen of bleomycin,
      ifosfamide, and cis-platinum (BIP) were analyzed in a series of 24 patients with
      recurrent cervical carcinoma in previously irradiated area. The doses were 30 mg,
      5000 mg/m2, and 50 mg/m2, respectively. Mesna was given simultaneously (6000
      mg/m2). None of the patients were treated with prior chemotherapy. All the
      patients were evaluable for toxicity and 20 for response. The median survival in
      patients evaluable for response was 9 months. No complete and 3 partial responses
      (15%) were observed, with a median duration of survival of 10+ months (range,
      9(+) -16). Stable disease was observed in 8 patients (40%) with a median duration
      of survival of 9.5 months (range, 6(+) -20). Progressive disease was observed in
      9 patients (45%) with a median duration of survival of 6 months (range, 3-25+).
      Four patients received one course only because of toxicity. One of these patients
      died at home 6 days after the first course, probably because of dehydration. The
      main toxicities were myelosuppression, renal impairment, alopecia, and
      nausea/vomiting. In conclusion, the BIP regimen has considerable toxicity. We
      were not able to confirm the high response rates earlier reported in pelvic
      recurrence inside a previously irradiated area. Emphasis in future studies must
      continue to be placed on the development of more active single agents and
      combinations.

PMID- 1379962
TI  - Paget's disease and melanoma of the vulva. Use of a panel of monoclonal
      antibodies to identify cell type and to microscopically define adequacy of
      surgical margins.
AB  - The ability of a panel of monoclonal antibodies generated in this laboratory to
      identify "pagetoid" melanoma cells and distinguish them from true Paget's
      adenocarcinoma cells in a retrospective analysis of vulvar neoplasms was
      investigated. Paraffin blocks of formalin and Carnoy's fixed tissue from 15 cases
      of vulvar Paget's disease and 11 cases of primary vulvar melanoma were retrieved
      and sections were incubated with the following panel of monoclonal antibodies:
      HMB45, a melanoma-specific monoclonal antibody; and 35 beta H11 and 34 beta E12,
      two different anti-cytokeratin monoclonal antibodies, to low molecular and high
      molecular weight cytokeratins, respectively. The anti-melanoma monoclonal
      antibody (HMB45) positively identified the melanoma cells, distinguishing them
      from normal melanocytes, in all 11 cases of melanoma. In contrast, the HMB45
      antibody failed to react with the intraepithelial neoplastic cells in all cases
      of Paget's disease. These latter malignant cells were strongly positive only with
      the monoclonal anti-low molecular weight cytokeratin antibody 35 beta H11. This
      latter antibody absolutely distinguished tumor cells from neighboring uninvolved
      squamous epithelium, which was positive only with the monoclonal antibody 34 beta
      E12. Using this panel of monoclonal antibodies, the surgical margins could also
      be better evaluated; in at least one case the surgical margin thought by
      histological evaluation to be free of tumor was demonstrated by
      immunocytochemistry to be positive for tumor. In the vulvectomy specimens
      obtained in both diseases, Paget's or melanoma cells were identified in sections
      histologically interpreted as free of tumor. Thus, a panel of monoclonal
      antibodies is able to identify, with high sensitivity and specificity, vulvar
      melanoma cells and absolutely distinguish them from vulvar Paget's cells and can
      help in evaluating surgical margins in a more accurate manner.

PMID- 1379963
TI  - Orgaran in hip fracture surgery.
AB  - Two studies evaluating the effect of Orgaran prophylaxis on the incidence of
      postoperative thrombosis in hip fracture surgery are reported. In one
      Scandinavian study, dextran was used in the comparative group, and in the US
      study, warfarin was used. In both, Orgaran was significantly more effective in
      reducing the frequency of deep vein thrombosis without producing an increase in
      bleeding complications or other side effects.

PMID- 1379964
TI  - Prevention of deep vein thrombosis following total hip replacement surgery by
      Orgaran. Summary.

PMID- 1379965
TI  - Orgaran (Org 10172): its pharmacological profile in experimental models.
AB  - Orgaran is a mixture of glycosaminoglycans extracted from animal mucosa. It
      consists of heparan, dermatan and chondroitin sulfate; a small proportion of
      heparan sulfate (4%) has high affinity for antithrombin III (AT III). Orgaran is
      devoid of heparin or heparin fragments. Orgaran catalyses the inactivation of
      factor Xa and thrombin. Compared to heparin and most low-molecular-weight
      heparins, Orgaran has a much higher anti-Xa/anti-IIa ratio. The inactivation of
      factor Xa is mediated by AT III and that of thrombin by both AT III and heparin
      cofactor II. Compared to heparin, which is a strong inhibitor of thrombin
      generation, Orgaran has only moderate inhibitory effects on thrombin generation.
      Orgaran shows minimal or no effects on platelet function in vitro or in vivo. It
      inhibits the formation of various types of thrombi (clot-like and mixed thrombi)
      with approximately the same potency as heparin. Both the high- and low-affinity
      fraction for AT III contribute to the antithrombotic activity. In contrast to
      heparin, Orgaran does not inhibit platelet deposition in experimental mixed
      thrombi unless very high doses of the heparinoid are used. Orgaran is more
      efficacious than heparin in preventing the extension of established venous
      thrombosis. Orgaran promotes less bleeding-enhancing activity than heparin in
      various experimental models. In addition, compared to heparin, it has only
      minimal effects on platelet degranulation during hemostatic plug
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379966
TI  - Anticoagulant mechanisms of Orgaran (Org 10172) and its fraction with high
      affinity to antithrombin III (Org 10849).
AB  - Orgaran (Org 10172), which has antithrombotic activity in man with apparently
      minimal bleeding side effects, is a mixture of low-molecular-weight heparan,
      dermatan, and chondroitin sulfates. The degrees to which the minimum
      concentrations of Orgaran, its fraction with high affinity for antithrombin III
      (Org 10849; AT III) and unfractionated heparin, which double the activated
      partial thromboplastin time (APTT) of pooled normal plasma, inhibit intrinsic
      activation of factor IX, factor X, and prothrombin were compared. Specific ELISAs
      were used to quantify the activation of each clotting factor. Factor IX
      activation, which began without a lag phase, preceded factor X and prothrombin
      activation by approximately 15 and approximately 25 s, respectively. When used at
      these functionally equivalent concentrations, heparin (2 micrograms/ml plasma),
      Orgaran (50 micrograms/ml plasma), and Org 10849 (20 micrograms/ml) could delay
      the onset of factor IX activation. Compared to control plasma, however, only
      Orgaran reduced the initial rate of factor IX activation. Heparin and Orgaran
      delayed the onset of factor X activation by 20 and 15 s, respectively, while Org
      10849 could not delay the onset of factor X activation. In addition, each
      anticoagulant delayed the onset of prothrombin activation. Thus, at
      concentrations which double the APTT of normal plasma, the combined actions of
      heparan and dermatan sulfate present in Orgaran can apparently suppress factor IX
      activation more effectively than heparin, and delay the onset of factor X
      activation nearly as effectively as heparin. The coordinated inhibition of factor
      IX and factor X activation by Orgaran may contribute to its antithrombotic
      effectiveness.

PMID- 1379967
TI  - Pharmacokinetic considerations on Orgaran (Org 10172) therapy.
AB  - Pharmacokinetic investigations on Orgaran (Org 10172) have been conducted by
      monitoring the following biological effects: plasma anti-Xa, anti-IIa and IIa
      generation-inhibiting (IIaGI) activities. In addition, a limited number of
      studies were conducted on the basis of concentrations of the No-affinity
      glycosaminoglyc(uron)an (NoA-GAG) fraction as determined by a competitive binding
      assay. In humans, widely different pharmacokinetic profiles for various
      biological effects were observed, with relatively short elimination half-lives
      for the anti-IIa and IIaGI activities of 4.3 +/- 3.5 and 6.7 +/- 3.2 h,
      respectively, but a relatively long elimination half-life of anti-Xa activity of
      24.5 +/- 9.6 h. These differences in half-life mainly reflect differences in the
      rate of elimination of individual components of Orgaran. Rapid elimination of
      some of these components may explain why twice daily dosing is required for
      optimal thrombosis prophylaxis with Orgaran. In a comparative study in healthy
      male volunteers, the pharmacokinetics of the following low molecular weight
      heparin(oid)s were determined after intravenous administration: Orgaran (3,750
      anti-Xa units), Fragmin (5,000 anti-Xa units), Fraxiparine (7,500 IC units) and
      Clexane (40 mg). Between these products, wide differences in pharmacokinetics
      were observed. Particularly, the half-lives of anti-Xa activity and IIaGI
      activity were much longer for Orgaran than for the other products. At the same
      time, a relatively low area under the curve of anti-IIa activity was observed.
      The absolute bioavailability of Orgaran following subcutaneous administration was
      determined on the basis of plasma anti-Xa and IIaGI activities and the NoA-GAG
      fraction concentrations. Absorption from subcutaneous tissues was found to be
      close to 100%, which is significantly higher than of heparin; a finding which
      indicates that the subcutaneous route is reliable for the administration of
      Orgaran. The elimination of Orgaran components occurs by renal and possibly non
      renal routes. With respect to anti-Xa activity, about 50% of the total clearance
      can be accounted for by urinary excretion. Therefore, in severe renal failure, a
      reduction of the maintenance dose of Orgaran would seem to be indicated. Studies
      on the influence of enzyme induction as a result of treatment with pentobarbital
      suggest that the pharmacokinetics of Lomoparan are relatively insensitive to
      changes in hepatic function. In a number of studies, the influence of conditions
      such as age, body weight and drug interactions were studied. Generally, only
      minor changes in the pharmacokinetic parameters of Orgaran were
      observed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1379968
TI  - Orgaran in heparin-induced thrombocytopenia.
AB  - Patients who develop heparin-induced thrombocytopenia (HIT) frequently need
      further anticoagulation to treat an ongoing thromboembolic problem or to prevent
      one. Orgaran (Org 10172), a low-molecular-weight (LMW) glycosaminoglycuronan, has
      shown a low frequency (10%) of cross-reactivity in vitro with sera containing the
      HIT antibody, in contrast to the much higher frequency of cross-reactivity
      (approximately 80%) shown by the LMW heparins. This paper summarises the results
      of intravenous or subcutaneous Orgaran treatment in 57 of 67 Australian patients,
      in whom the diagnosis of HIT was reasonably confirmed by exclusion of other
      causes of thrombocytopenia and by objective tests. The presenting indications for
      Orgaran were: continuous venovenous haemofiltration and haemodialysis (n = 21),
      thrombo-embolism treatment (n = 23), thrombo-embolism prophylaxis (n = 10), and
      anticoagulation for coronary artery by-pass graft (n = 4), peripheral by-pass
      graft surgery and plasmapheresis (n = 1 each). The results showed Orgaran to be a
      safe, well-tolerated, effective (successful treatment in over 90% of patients)
      anticoagulant in patients with a high thrombotic and/or bleeding risk even if
      critically ill and requiring haemofiltration. The complete results of the world
      wide study in 161 patients confirmed not only these clinical findings in the
      subgroup of 57 Australian patients, but also the low cross-reactivity (12%) of
      Orgaran with the HIT serum factor.

PMID- 1379969
TI  - Orgaran in the prevention of deep vein thrombosis in stroke patients.
AB  - Venous thrombo-embolism is a common complication in patients with acute ischaemic
      stroke. Without prophylaxis, deep vein thrombosis occurs in 60-75% of patients
      with dense hemiplegia, usually in the paralyzed limb, and 1-2% suffer fatal
      pulmonary embolism. Orgaran (Org 10172, low-molecular-weight heparinoid) has been
      evaluated for the prevention of deep vein thrombosis in patients with acute
      ischaemic stroke in two studies. In a double-blind study, 75 patients were
      randomized to receive Orgaran (50 patients) in a loading dose of 1,000 anti-Xa
      units intravenously followed by 750 anti-Xa units subcutaneously 12-hourly or
      placebo (25 patients). Deep vein thrombosis occurred in 2 of 50 (4%) in the
      Orgaran group and 7 of 25 (28%) in the placebo group (p = 0.005). The
      corresponding rates for proximal deep vein thrombosis were 0 and 16%,
      respectively (p = 0.01). There was one major haemorrhage in the treated group and
      one minor haemorrhage in the placebo group. In the second study, the safety and
      efficacy of Orgaran was compared with unfractionated heparin in the prevention of
      deep vein thrombosis in a double-blind randomized trial. Eighty-seven patients
      with marked lower limb paralysis secondary to stroke were randomized to receive
      Orgaran (45 patients) in a dose of 750 anti-factor Xa units subcutaneously 12
      hourly or unfractionated heparin (42 patients) in a dose of 5,000 units
      subcutaneously 12-hourly. Venous thrombosis occurred in 4 of 45 (8.9%) of the
      Orgaran group and 13 of 42 (31%) in the unfractionated heparin group (2p =
      0.014). The corresponding rates for proximal vein thrombosis were 4.4 and 11.9%,
      respectively (2p = 0.255).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1379970
TI  - Studies of Org 10172 in patients with acute ischemic stroke. TOAST Study Group.
AB  - This report presents data from pilot studies of Org 10172 in the management of
      patients with acute ischemic stroke. The studies have established a potentially
      optimal dosage and treatment regimen and have provided information for the
      development of a large randomized trial. The trial of Org 10172 in acute stroke
      treatment is now underway in the United States.

PMID- 1379971
TI  - Protection by albumin against the pro-oxidant actions of phenolic dietary
      components.
AB  - Synthetic and natural phenolic compounds are increasingly used in food
      preservation. Carnosol and carnosic acid (active components of rosemary extract),
      flavonoids (morin, quercetin, fisetin, myricetin), other plant phenolics
      (gossypol) and propyl gallate may protect lipids against oxidative damage but
      have the potential to increase damage to non-lipid constituents of foods, such as
      carbohydrates and DNA. Thus, in the presence of ferric EDTA and H2O2, they can
      form highly reactive hydroxyl radicals that can degrade the sugar deoxyribose
      and/or accelerate DNA degradation by means of a ferric-bleomycin complex. Human
      and bovine serum albumin afford considerable protection against damage to
      deoxyribose and DNA mediated by the above reactions. It is suggested that, given
      the fortification of foods with iron and EDTA and the use of phenolic substances
      as 'antioxidant' food additives, the addition of albumin might afford some
      protection.

PMID- 1379972
TI  - A study of uric acid pretreatment for the protection of rat gastric mucosa
      against toxic damage.
AB  - Uric acid was evaluated for its potential to protect the gastric mucosa against
      the injuries caused by 80% ethanol, 0.6 m-HCl and 0.2 M-NaOH in rats. Uric acid
      at doses of 50, 100 or 300 mg/kg body weight provided dose-dependent protection
      against the ulcerogenic effects of all three agents. Other effects caused by
      ethanol only were studied. Serum uric acid concentrations were statistically
      significantly increased by both uric acid and ethanol treatments. Treatments of
      rats by gavage with 1 ml 80% ethanol was found to cause depletion of stomach-wall
      mucus, to lower the concentrations of protein, nucleic acids and non-protein
      sulphydryl groups in the stomach wall, and to cause histopathological lesions,
      including necrosis, erosions, congestion and haemorrhage, of the stomach wall.
      Treatment with uric acid, at doses of 50, 100 or 300 mg/kg body weight, by
      gavage, provided some measure of protection against all of these effects, and the
      protection was generally dose dependent. The protective effects of uric acid
      against damage to the gastric-wall mucosa may be mediated through its effects on
      mucus production and non-protein sulphydryl concentrations, and/or its free
      radical scavenging properties.

PMID- 1379973
TI  - p185 HER2/neu epitope mapping with murine monoclonal antibodies.
AB  - In order to obtain further information on the biological role of the HER2/neu
      oncoprotein, 7 new monoclonal antibodies (MAbs) were produced against the
      p185HER2 extracellular domain. These MAbs, together with two others previously
      produced, were used to investigate the p185HER2 expression in breast carcinomas
      and compare the recognized antigenic determinants. The 7 reagents (MGR4,5,6,7,8,9
      and 10), were shown to define five distinct epitopes. Three of these MAbs
      (MGR5,7,10), as well as one previously produced (MGR2), recognize the same
      epitope (Epitope-1) which seems, therefore, to be highly immunogenic for the
      murine immune system. Epitope-2 recognized by the MGR4 MAb, appears to be closely
      related to epitope-1 due to a cross inhibition between MGR4 and MGR10, but not
      MGR2. Epitope-2 is the only one of the 5 also present on the product of the neu
      oncogene, the rat analogue of the human HER2/neu gene. None of the reagents
      against epitope-1 and epitope-2 were found to mediate receptor internalization,
      whereas MGR6 as well as a previously produced MAb (MGR3), both of which define
      epitope-3 and MGR8 which defines epitope-4, were found to do so. Epitope-4 like
      the neu-specific peptide recognized by the reference c-neu Ab3 MAb, was
      detectable on all p185HER2 positive breast cancer, independently from the
      quantitative content of the oncoprotein, at variance with the other 4 epitopes
      whose availability on p185HER2 for the relevant MAbs varied with the degree of
      overexpression. Epitope-5, recognized by the MGR9 MAb, on the contrary to the
      other epitopes, was prevalently localized at the basal membrane level of the
      tumor nodule.

PMID- 1379974
TI  - Characterization and nucleotide sequences of the variable regions of a monoclonal
      antibody against alpha-fetoprotein.
AB  - alpha-Fetoprotein (AFP) is a well-known tumor marker of hepatocellular carcinoma
      (HCC). Monoclonal antibodies against AFP possessing specific binding ability to
      HCC are potential candidates for immunoscintigraphy and immunotherapy. A new
      monoclonal antibody against AFP (0325-6-9) was isolated. Its specificity and
      targeting tumor ability were characterized by enzyme-linked immunosorbent assay
      (ELISA), cell immunostain and complement killing. These results suggest that 0325
      6-9 is specific to hepatoma cells. The nucleotide sequences of variable regions
      of 0325-6-9 were determined by M13 dideoxynucleotide sequencing method. With the
      information of nucleotide sequence, this antibody then could be modified by
      recombinant technology for its usage in in vivo diagnosis and immunotherapy.

PMID- 1379975
TI  - Production and characterization of mouse monoclonal antibodies to native human
      myeloperoxidase.

PMID- 1379976
TI  - [Binding of LPS to CD14].
AB  - The 53 kDa glycoprotein CD14 (cluster of differentiation No. 14, defined by
      monoclonal antibodies of the 1st Leukocyte Typing Workshop) is expressed on
      monocyte surfaces and was identified 1990 as an endotoxin receptor (1). The
      binding of endotoxin to CD14 was mediated by a LPS-binding protein (LBP) present
      in serum.

PMID- 1379977
TI  - [Endotoxin neutralization by soluble CD14 in vitro].

PMID- 1379978
TI  - Preliminary studies on the interaction of TNF alpha and IFN gamma with alpha 2
      macroglobulin.
AB  - The binding of 125I-labelled recombinant human TNF alpha and IFN gamma to
      isolated human blood alpha 2-macroglobulin has been investigated using molecular
      sieving procedures and non-denaturing PA gel electrophoresis in combination with
      autoradiography. These studies revealed that both cytokines readily bind to the
      electrophoretically fast form of alpha 2M generated by methylamine or protease
      treatment of this protein. PAGE/SDS gel investigations indicated that TNF alpha
      bound non-covalently while the IFN gamma interaction was covalent in nature.
      Preliminary competition studies also indicate that cold TNF alpha and IL-2 are
      more effective than cold IFN gamma at inhibiting the binding of labelled IFN
      gamma to alpha 2M. Bioassays revealed that "native" alpha 2M or its derivatives
      at 2 mg/ml concentration did not impair the antiproliferative effects of TNF
      alpha and IFN gamma on susceptible bladder tumour cell lines. Furthermore they
      did not interfere in the induction of Class II antigen expression by IFN gamma on
      inducible cell lines or in a 2-site ELISA assay for TNF.

PMID- 1379979
TI  - Role of the endothelial adhesion molecule VCAM in murine cardiac allograft
      rejection.
AB  - Murine heterotopic cardiac isografts (C57B1/6----C57B1/6) undergo transient, non
      destructive inflammation that is characterized by the acquisition of
      microvascular endothelial reactivity with the antibody MECA 32. Cardiac
      allografts (C57B1/6----DBA/2) undergo destructive inflammation that is
      characterized by the acquisition of reactivity with the antibody M/K-2, in
      addition to MECA 32. M/K-2 recognizes the murine endothelial adhesion molecule,
      VCAM-1. Hence, there appear to be antigen-dependent and antigen-independent forms
      of graft inflammation. Treatment of cardiac allograft recipients with 200
      micrograms/day M/K-2 antibody retarded graft loss by only a few days, and did not
      interfere significantly with leukocytic infiltration, as detected by limiting
      dilution analysis of graft-reactive CTL, despite the fact that large amounts of
      M/K-2 could be detected on graft microvascular endothelia and in the peripheral
      blood as rejection progressed. These data indicate that VCAM is apparently not
      essential for the leukocytic infiltration and subsequent rejection of cardiac
      allografts, and is not involved in leukocytic infiltration of murine cardiac
      isografts.

PMID- 1379980
TI  - Two chicken monoclonal antibodies specific for heterophil Hanganutziu-Deicher
      antigens.
AB  - Two chicken monoclonal antibodies (MAbs), HU/Ch2-7 and HU/Ch6-1, against
      heterophil Hanganutziu-Deicher (HD) antigens with N-glycolylneuraminic acid
      (NeuGc) at a terminal carbohydrate were established by cell fusions using chicken
      B cell lines lacking thymidine kinase and spleen cells from chickens immunized
      with II3NeuGc alpha-LacCer (HD3). The reactivities of these MAbs against several
      gangliosides including NeuGc-containing glycosphingolipids were examined by a
      thin-layer chromatography/immunostaining method. MAb HU/Ch2-7 (IgG) reacted
      strongly with HD3 and IV3NeuGc alpha-nLc4Cer (HD5) and weakly with VI3NeuGc alpha
      nLc6Cer (HD7) and 4-O-acetyl-HD3. HU/Ch6-1 (IgG) reacted with HD3 and HD5, but
      did not react with the other HD antigens. The reactivities of these MAbs against
      HD antigen were greatly reduced by pre-treatment of the antigen with
      neuraminidase. These MAbs did not react with N-acetylneuraminic acid-containing
      gangliosides (GM1 and GM3). These results indicate that these two chicken MAbs
      are directed toward the antigenic epitope containing the NeuGc.

PMID- 1379981
TI  - Immunological characterization of an immunomodulatory epitope in S
      antigen/arrestin with a sequence motif common to tumor necrosis factor alpha.
AB  - Some monoclonal antibodies (mAbs) to retinal S-antigen recognize a
      phylogenetically conserved epitope (S2) in the N-terminal part of the protein.
      These antibodies have been shown to inhibit the induction of experimental
      autoimmune uveoretinitis by S-antigen in rats. Using Pepscan method, we localized
      this epitope on the amino acid (aa) residues 40-50, i.e., PVDGVVLVDPE (peptide
      S2). MAb binding was confirmed by ELISA, competition-ELISA and dot blot. Other S
      antigen peptides with homologies to epitope S2 and peptides exhibiting the
      pathogenic and T-cell proliferation inducing sites did not bind these mAbs.
      Epitope S2 displays an immunological crossreactivity with human tumor necrosis
      factor (TNF) alpha. Recent results indicate that both peptide S2 and a peptide
      from human TNF alpha (aa residues 31-53) containing the common sequence motif
      GVxLxD induce TNF alpha production in monocytes. We analyzed the fine structure
      of the common epitope by studying mAb binding in an amino acid residue exchange
      experiment.

PMID- 1379982
TI  - In situ islet T cell receptor variable region gene usage in the nonobese diabetic
      mouse.
AB  - Several features of the genetics and immunopathology of diabetes in the nonobese
      diabetic (NOD) mouse, which spontaneously develops type I diabetes, are shared
      with the human disease. Immunohistochemical studies support the concept that T
      lymphocytes are the major components of inflammatory cells in the pancreatic
      islets and these cells may play a critical role in the destruction of the beta
      cells leading to diabetes. Therefore, we examined whether particular TCR-beta
      variable region genes were utilized by in situ islet T cells at different stages
      (4 - 5, 7, 14 - 15 and 16 weeks of age) of the disease process. Dot-blot
      hybridization was performed using RNA prepared from isolated islets, thymus,
      spleen, peripheral blood leukocytes and axillary lymph nodes of 10 to 15 mice
      pooled for each data point. Ten different TCR V-beta probes were used for the
      analyses. Limited usage of islet V-beta genes was observed only at the early
      prediabetic stage (4 - 5 weeks old) of the disease. At later stages of the
      disease (7 - 16 weeks old), no preferential usage of TCR genes was observed in
      the islets compared to those of peripheral lymphoid organs. These data suggest
      that only certain types of T cells bearing particular TCR V-beta genes may be
      responsible for initiating and perpetuating infiltration of immune cells into the
      islets and these particular T cells are only identified at the very early stages
      of the autoimmune process.

PMID- 1379983
TI  - New antigenic clusters on human thyroglobulin defined by an expanded panel of
      monoclonal antibodies.
AB  - Twenty-seven hybridomas secreting monoclonal antibodies (mAb) directed against
      new antigenic clusters on human thyroglobulin (hTg) were obtained by fusion of
      the mouse myeloma P3-X63-Ag8 653 with spleen cells from BALB/c mice immunized
      with a mixture of hTg and six anti-hTg mAb with the aim of masking the
      corresponding antigenic clusters previously reported. Fourteen mAb were selected,
      produced in ascitic fluid and characterized. All these mAb were of the IgG1
      subclass. Five new antigenic clusters on the hTg molecule were defined by the 14
      mAb, extending the initial antigenic map of hTg to 11 clusters. These mAb were
      used in an attempt to probe the interaction between hTg and the autoantibodies
      from patients with Hashimoto's thyroiditis who do not recognize antigenic cluster
      II, a cluster whose recognition by anti-hTg autoantibodies is significantly
      associated with thyroid disorders.

PMID- 1379984
TI  - Role of the mononuclear phagocyte as an antigen-presenting cell for human gamma
      delta T cells activated by live Mycobacterium tuberculosis.
AB  - gamma delta T cells, both human and murine, have been found to be highly
      responsive to mycobacterial antigens. However, the role and function of gamma
      delta T cells in the immune response to Mycobacterium tuberculosis remain largely
      unknown. In earlier studies, we demonstrated that monocytes infected with live M.
      tuberculosis were particularly effective inducers of human peripheral blood gamma
      delta T cells. The present studies were performed to further characterize the
      interaction between human mononuclear phagocytes, gamma delta T cells, and live
      M. tuberculosis, in comparison with CD4+ T cells. First, we found that resting
      gamma delta T cells expanded in vitro by live M. tuberculosis were specific for
      M. tuberculosis, and that heat killing and washing the mycobacteria removed the
      antigen(s) for gamma delta T cells. In contrast, the heat-killed mycobacteria
      retained significant antigenicity for CD4+ T cells. Second, live M. tuberculosis
      expanded gamma delta T cells from healthy tuberculin-positive donors did not
      respond significantly to the antigens in M. tuberculosis culture filtrate,
      including the 65- and 71-kDa mycobacterial heat shock proteins. Third, the
      activation of gamma delta T cells by live mycobacteria was dependent on antigen
      presenting cells, and mononuclear phagocytes were found to be very efficient
      antigen-presenting cells both for resting peripheral blood gamma delta T cells
      and for activated expanded gamma delta T cells. The mononuclear phagocyte carried
      the necessary costimulatory factors necessary for gamma delta T-cell
      proliferation. Fourth, the antigen repertoire and HLA requirements for CD4+
      memory T cells and those for gamma delta T cells appear to be quite distinct from
      each other. CD4+ T cells recognized both soluble protein antigens and whole
      organisms in a class II major histocompatibility complex-restricted manner,
      whereas gamma delta T cells appeared to recognize only constituents associated
      with the whole organism and were not restricted by class I or class II major
      histocompatibility complex molecules. Finally, the assay system described to
      expand and purify responding CD4+ and gamma delta T cells after stimulation with
      live M. tuberculosis represented a simple approach to the direct comparison of
      these two T-cell populations in the interaction with mononuclear phagocytes
      infected with M. tuberculosis. Such studies provide insight not only into the
      relative roles of human CD4+ and gamma delta T cells in the human immune response
      to intracellular bacterial pathogens such as M. tuberculosis but also into the
      basic biologic role of human gamma delta T cells in antimicrobial immunity.

PMID- 1379985
TI  - Synthetic peptides representing epitopes of outer membrane protein F of
      Pseudomonas aeruginosa that elicit antibodies reactive with whole cells of
      heterologous immunotype strains of P. aeruginosa.
AB  - By using the published amino acid sequence for mature outer membrane protein F of
      Pseudomonas aeruginosa, a computer-assisted analysis was performed to identify
      sites with potential as surface-exposed, antigenic regions located throughout the
      length of the protein molecule. Synthetic peptides 13 to 15 amino acid residues
      in length were synthesized for 10 such regions. Mice were immunized with each of
      the 10 synthetic peptides conjugated to keyhole limpet hemocyanin. An enzyme
      linked immunosorbent assay (ELISA) of the antisera was performed by using each of
      the synthetic peptides as the ELISA antigen to verify that immunoglobulin G (IgG)
      antibodies capable of reacting with the peptide used as immunogen were elicited
      by each peptide. Each of the antipeptide antisera was screened for the presence
      of IgG antibodies that could bind to the surface of intact cells of strains
      representing the seven heterologous Fisher-Devlin immunotypes of P. aeruginosa by
      use of an ELISA with whole cells of the various strains as the ELISA antigen.
      Three peptides elicited antibodies capable of reacting with whole cells of all
      seven immunotype strains. Peptide 10, corresponding to amino acid residues 305 to
      318, elicited whole-cell-reactive antibodies at high titers. Peptide 9,
      corresponding to amino acid residues 261 to 274, elicited whole-cell-reactive
      antibodies at more intermediate titers. Peptide 7, corresponding to amino acid
      residues 219 to 232, elicited such antibodies only at low titers. The carboxy
      terminal portion of the mature protein appears to be the immunodominant portion.
      In particular, peptides 10 (NATAEGRAINRRVE) and 9 (TDAYNQKLSERRAN) appear to have
      potential for use as immunogens in a synthetic vaccine for immunoprophylaxis
      against infections caused by P. aeruginosa. Antisera from mice immunized with
      either peptide 9 or 10 mediated opsonophagocytic uptake by human
      polymorphonuclear leukocytes of wild-type cells of P. aeruginosa but exhibited no
      opsonic activity against a protein F-deficient mutant of P. aeruginosa.

PMID- 1379986
TI  - Suppression of C3H/HeJ cell activation by lipopolysaccharide endotoxin.
AB  - Earlier studies in our laboratory showed that the lipopolysaccharide (LPS) of
      Salmonella typhi, which fails to activate B lymphocytes of C3H/HeJ mice, can
      suppress proliferation and polyclonal antibody synthesis by these cells when they
      are stimulated by polyclonal activators. In order to determine what stage of the
      cell cycle was blocked, resting B cells from C3H/HeJ spleens were activated by
      using different mitogens in the presence of inhibitory concentrations of LPS and
      analyzed by flow cytometry, using acridine orange to stain DNA and RNA. LPS was
      found to inhibit the progression of cells into the G1 stage of the cell cycle.
      Furthermore, [3H]uridine uptake studies showed that RNA synthesis is inhibited
      during the early phase of activation. These results indicate that inhibition by
      LPS of the signalling process occurs during a critical period of the cell cycle
      when the cells become susceptible to the inhibitory effects of LPS. To examine
      whether LPS acts only on B cells or whether it can suppress other immunocompetent
      cells from C3H/HeJ mice, studies were carried out on activated thymocytes and
      macrophages. LPS was found to inhibit thymocyte proliferation stimulated by
      concanavalin A or the combination of phorbol myristate acetate and ionomycin.
      Prostaglandin E2 synthesis by macrophages was also blocked by LPS. Thus, LPS is a
      potent inhibitor of the functioning of the major immunocompetent cells of C3H/HeJ
      mice.

PMID- 1379987
TI  - Identification of a beta 1 integrin on Mycobacterium avium-Mycobacterium
      intracellulare.
AB  - Mycobacterium avium-Mycobacterium intracellulare (MAI) is an opportunistic
      intracellular pathogen responsible for the highest incidence of disseminated
      bacterial infection in patients with AIDS. Treatment of the infection is
      extremely difficult and has shown limited efficacy. A critical event in the
      initiation of a variety of bacterial infections involves the adherence of
      bacteria to host cell surfaces. In the present study, we have shown that MAI
      organisms bind avidly to extracellular matrix proteins such as laminin, collagen
      I, and fibronectin in an in vitro attachment assay. Immunoblot analysis of a
      sonicate of MAI with polyclonal antibodies against different integrin receptors
      indicated that the sonicate cross-reacts with polyclonal antibodies against a
      human laminin-binding integrin, alpha 3 beta 1, and a human fibronectin-binding
      integrin, alpha 5 beta 1, although it is reactive with only the beta 1 subunit in
      the case of both antisera. Antibodies against the alpha 3 beta 1 and alpha 5 beta
      1 integrins specifically inhibited the binding of MAI to laminin, collagen I, and
      fibronectin by 70 to 97%, depending on the ligand, suggesting that the attachment
      of MAI to these extracellular matrix proteins may be mediated by a beta 1
      integrin. Furthermore, the attachment of MAI to laminin, collagen I, and
      fibronectin was found to be cation dependent. MAI may use this and other beta 1
      containing integrins to adhere and penetrate through basement membrane structures
      that underlie host cell linings. An understanding of the mechanism of attachment
      and a definition of the adhesive molecules on the surface of MAI may open up new
      approaches to the prevention of serious infection caused by this organism.

PMID- 1379989
TI  - Mapping of Candida albicans oligomannosidic epitopes by using monoclonal
      antibodies.
AB  - Six monoclonal antibodies (MAbs) from various laboratory sources (EB-CA1, EB-CA2,
      H5, AF1, C6, and 5B2), reacting with the polysaccharidic moieties of Candida
      albicans mannoproteins, were used for epitope mapping by an enzyme-linked
      immunosorbent assay (ELISA) with neoglycolipids and by Western blotting
      (immunoblotting) of a C. albicans germ tube extract. The ELISA involved
      neoglycolipids constructed from three families of oligomannosides released by
      sequential depolymerization of C. albicans phosphopeptidomannan by acid
      hydrolysis (NGLH), beta-elimination (NGLO), and acetolysis (NGLA). All of the
      MAbs exhibited low reactivities against NGLO. MAbs EB-CA1, EB-CA2, and H5 reacted
      mainly against NGLA, and MAbs C6 and AF1 recognized mainly NGLH, whereas MAb 5B2
      reacted with both families of neoantigens. When this method was compared with
      Western blotting, strong reactivity to NGLA was associated with the presence of
      epitopes shared by high-molecular-weight mannoproteins, whereas strong reactivity
      to NGLH was associated with a reactivity to a family of 14- to 18-kDa antigens.
      The reactivity of MAb 5B2 was associated with both high-molecular-weight
      mannoproteins and the 14- to 18-kDa antigens. In relation to the present
      knowledge about the structure of the C. albicans phosphopeptidomannan
      oligomannosidic repertoire, these results provide preliminary data concerning the
      molecular basis of the recognition of mannopyranosyl sequences by MAbs and their
      distribution among C. albicans mannoproteins.

PMID- 1379988
TI  - Borrelia burgdorferi HSP70 homolog: characterization of an immunoreactive stress
      protein.
AB  - The gene encoding an immunoreactive Borrelia burgdorferi HSP70 homolog was
      isolated and characterized. The predicted amino acid sequence of this spirochetal
      protein confirms that this gene encodes a member of the HSP70 family of proteins.
      Although there appears to be a single copy of this gene on the spirochetal
      chromosome, two distinct transcripts hybridizing to the hsp70 probe are detected
      in RNA isolated from B. burgdorferi. The amount of spirochetal HSP70 RNA
      transcripts is shown to be thermally regulated. Antibodies in the serum of three
      Lyme arthritis patients and cloned T-cell lines isolated from one patient with
      Lyme arthritis recognize the expressed recombinant HSP70, indicating that it is
      an immunologically important spirochetal antigen. Antibodies in a rabbit
      antiserum, as well as antibodies in the serum of two of three Lyme arthritis
      patients examined, bound to expressed truncated recombinant HSP70s with 250 amino
      acids deleted from either the amino or carboxy terminus of the protein. However,
      antibodies in the serum of three Lyme arthritis patients, which were reactive
      with spirochetal HSP70, did not cross-react with human HSP70 proteins.

PMID- 1379990
TI  - Inhibition of bactericidal activity of anticapsular antibody by nonspecific
      antibodies reactive with surface-exposed antigenic determinants on Actinobacillus
      pleuropneumoniae.
AB  - In an attempt to understand the mechanism of serum resistance in Actinobacillus
      pleuropneumoniae, in the present study we examined various interactions among the
      bacterial surface constituents, serum antibodies, and complement. Analysis of
      swine sera revealed the presence of anticapsular antibodies in convalescent-phase
      sera but not in preimmune sera. Both types of sera contained antibodies which
      reacted with each of 14 polypeptides present in saline extracts of the bacteria.
      Absorption of the preimmune sera with intact bacteria depleted antibodies to two
      of the polypeptides (27 and 32 kDa) and high-molecular-weight (greater than
      97.4,000) components which did not stain with Coomassie blue. Data derived from
      complement consumption and C3-binding experiments indicated that the organism was
      capable of initiating complement activation and binding C3 during incubation in
      preimmune and immune sera. Experiments designed to evaluate the bactericidal
      effectiveness of anticapsular antibody revealed that the purified antibody was
      bactericidal only when preimmune sera absorbed with intact bacteria were used as
      a source of complement. The bactericidal effects of anticapsular antibody and
      absorbed preimmune sera were inhibited in a dose-dependent manner by heat
      inactivated preimmune sera and immunoglobulin G derived from the sera. The
      inhibitory activity of the preimmune sera was neutralized by preincubating the
      sera with column fractions of the saline extract which contained either the 27-
      or the 32-kDa polypeptide. These results indicate that serum resistance in A.
      pleuropneumoniae 4074 could be related to inhibition of the bactericidal action
      of anticapsular antibody by nonspecific antibodies which recognize surface
      exposed epitopes on the polypeptides.

PMID- 1379991
TI  - Characterization of a major hemagglutinin protein from Mycoplasma gallisepticum.
AB  - Mycoplasma gallisepticum cell membranes were used to immunize mice to produce
      monoclonal antibodies to cell surface proteins. Three monoclonal antibodies were
      chosen for further characterization. All three reacted in immunoblots with an M.
      gallisepticum protein band of M(r) approximately 67,000 (designated pMGA). By
      using immunoelectron microscopy, pMGA was shown to be located on the cell
      surface. When M. gallisepticum whole cells were treated with up to 250 micrograms
      of trypsin per ml for 30 min, the only major protein lost from the cell surface
      as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed
      by Western immunoblot transfer was pMGA. Two of the pMGA-specific monoclonal
      antibodies inhibited hemagglutination of chicken erythrocytes by M. gallisepticum
      S6, suggesting a role for pMGA in the attachment of M. gallisepticum to chicken
      erythrocytes. Sequencing the amino terminus of pMGA yielded 17 amino acids with
      no significant homology with the Mycoplasma pneumoniae attachment protein P1 or
      any other protein in the GenBank, Swiss-Prot, and EMBL data bases.

PMID- 1379992
TI  - Bacterial motility is a colonization factor in experimental urinary tract
      infection.
AB  - In an experimental urinary tract infection of the mouse, colonization of the
      urinary bladder by isogenic strains of Salmonella enterica serovar Typhimurium
      was found to depend on the motility of the bacteria. Strains were obtained by
      genetic recombination between a highly motile O-6,7 and a poorly motile O-4,5,12
      strain. The O antigen did not interfere with the colonization, whereas motility
      did; flagellated and motile O-6,7 and O-4,5,12 bacteria colonized the bladder
      equally well.

PMID- 1379993
TI  - Hyaluronan (hyaluronic acid) and hyaluronectin in the extracellular matrix of
      human breast carcinomas: comparison between invasive and non-invasive areas.
AB  - We performed quantitative determination of the distribution of hyaluronan
      (hyaluronic acid, HA) and the HA-binding protein, hyaluronectin (HN), 2
      components of the extracellular matrix of tumor desmoplasia, within 71 human
      breast carcinomas. Results showed that HA and HN were more elevated in tumoral
      than in non-tumoral adjacent tissue, and that the peripheral invasive area of
      tumors contained increased levels of HA and HN as compared with the central non
      invasive area (p less than 10(-3) and p less than 10(-5) respectively). HN and HA
      levels of 61 ductal carcinomas were related to the histological grade of tumors;
      no significant difference was found between grades for HA; HN was found to be
      significantly lower in grade III than in grade II tumors (p less than 0.01). HA
      and HN rates were correlated in grade I and grade II tumors and were not
      correlated in grade III. Mean percentage of HA saturation level by HN for whole
      tumors was found to be less than 4%, indicating that HA is essentially free of
      proteins and could be used as a target for cancer diagnosis or therapy.

PMID- 1379994
TI  - Enhancement of hepatitis-B surface-antigen expression by 5-azacytidine in a
      hepatitis-B-virus-transfected cell line.
AB  - The human hepatoblastoma-derived cell line HB611 secretes hepatitis-B surface
      antigen (HBsAg) and hepatitis-B e antigen (HBeAg) into the medium. Hepatitis-B
      virus (HBV) DNA integrated into the cellular genome was found to be
      hypermethylated. When the cells were treated with 5-azacytidine for 3 days, the
      level of HBsAg in the medium increased, while the level of HBeAg remained
      constant. The level of alpha-fetoprotein (AFP) decreased with the 5-azacytidine
      treatment. Southern blot analysis of DNA digested with HpaII or MspI showed that
      5-azacytidine treatment resulted in hypomethylation of the integrated HBV DNA,
      suggesting that 5-azacytidine increased HBsAg production in the cells through
      hypomethylation of the HBV genomic DNA.

PMID- 1379995
TI  - Protein-kinase-C inhibitor calphostin C reduces B16 amelanotic melanoma cell
      adhesion to endothelium and lung colonization.
AB  - We recently reported that the Ca(2+)- and phospholipid-dependent protein kinase,
      protein kinase C (PKC), was involved in rat Walker carcinosarcoma cell adhesion
      to large-vessel endothelium. We extended our studies to explore the role of this
      kinase in the adhesion to small-vessel endothelium and lung colonization of
      murine B16 amelanotic melanoma (B16a). Subpopulations of B16a cells, which differ
      in lung-colonization potentials, were isolated by centrifugal elutriation from
      solid tumors. In this study, we demonstrate that cells from a high metastatic sub
      population (HM340), when compared with cells from a low metastatic sub-population
      (LM180), exhibit elevated levels of total cellular as well as membrane-bound PKC.
      The increase in PKC in cells from the HM340 correlates positively to their
      increased ability to adhere to murine pulmonary-microvessel endothelial-cell
      monolayer, and to form pulmonary colonies in syngeneic mice. Calphostin C, a
      potent and selective PKC inhibitor, decreases in a dose-dependent manner the
      adhesion to endothelium and the lung colonization of cells from both the low and
      the high metastatic sub-populations with IC50 at sub-micromolar concentrations.
      In conclusion, our results suggest that PKC may be a key element in regulating
      tumor-cell metastasis and that PKC inhibitors may be anti-metastatic agents.

PMID- 1379996
TI  - A modified method for the differential staining of spermatozoa using alcoholic
      acidic silver nitrate.
AB  - Differential silver staining patterns have been demonstrated in mammalian
      spermatozoa, using an aqueous silver nitrate reagent. In the present study,
      mouse, rabbit, and human spermatozoa were stained using a modification of the
      earlier method. In the modified method, an alcoholic acidic silver nitrate stain,
      with subsequent differentiation in alcoholic ammonia, was used. This method
      enhanced the intensity of staining of the head, mid-piece, and tail. In
      particular, marked differentiation of the acrosomal, subacrosomal, and
      postacrosomal regions was obtained, which facilitated determination of acrosomal
      integrity. Moreover, background interference was reduced, yielding better clarity
      of the stained smears. The staining was carried out in the cold. This modified
      technique offers an advantage in the assessment of sperm morphological anomalies
      and membrane and acrosomal integrity, and is a simple, reliable, and useful
      method for the evaluation of sperm function.

PMID- 1379997
TI  - Purification of a low molecular weight calf pineal peptide controlling DNA
      transcription in vitro.
AB  - A low molecular factor showing high specific activity in the control DNA of
      transcription in vitro was isolated from aqueous ultrafiltered calf pineal gland
      extracts. The active factor was purified by means of Gel filtration on Sephadex G
      25 and G-10, thin layer chromatography on aluminum sheet cellulose and high
      performance liquid chromatography using a Supelcosil LC 318 reverse phase column.
      The purified pineal factor was characterized as a peptide of low molecular weight
      (of about 1200 Dalton) containing glutamic acid, leucine, glycine, threonine and
      alanine in their approximate molar ratio, referred to glycine taken as 1: glycine
      1, threonine 1, leucine 1, alanine 6, glutamic acid 2. Studies of the aminoacid
      sequence by N-terminal analysis using the automated Edman degradation procedure,
      were unsuccessful, suggesting the presence of a blocked NH2 group. The purified
      peptide appears to be different from peptide factors till now isolated from
      pineal gland.

PMID- 1379998
TI  - Identification of vimentin in rat peritoneal mast cells and its phosphorylation
      in association with histamine release.
AB  - Stimulation of rat peritoneal mast cells with histamine releasers, such as
      compound 48/80 and substance P, caused a similar pattern of protein
      phosphorylations: the molecular weights of the two major phosphorylated proteins
      were 45 kDa and 59 kDa. When rat mast cells permeabilized with beta-escin were
      exposed to Ca2+ at concentrations higher than 0.6 microM, phosphorylated proteins
      of identical molecular weight were also detected. By a radioimmunoprecipitation
      assay using anti-vimentin mouse monoclonal antibody, the 59 kDa protein was
      identified as vimentin, one of the intermediate cytoskeletal proteins. Moreover,
      it became apparent that the phosphoamino acid in phosphorylated vimentin was a
      serine residue. Sequential changes in vimentin phosphorylation were similar to
      that of histamine release elicited by histamine releasers: phosphorylation took
      place within 5 s of stimulation and reached a maximum within 10 s. When
      permeabilized mast cells were treated with calphostin C, a specific protein
      kinase C inhibitor, phosphorylation was markedly inhibited. Fluorescence images
      of mast cells stained with FITC-labelled anti-vimentin antibody showed
      filamentous structures surrounding the granules in the cytoplasm. However, after
      exposure to compound 48/80, the filamentous structures promptly disappeared and a
      dim fluorescence was observed homogeneously in the cell indicating that a rapid
      depolymerization of vimentin had taken place. From the present study, it became
      clear that when rat peritoneal mast cells were stimulated, vimentin was rapidly
      phosphorylated by protein kinase C and this phosphorylation process seems to be
      related to histamine release.

PMID- 1379999
TI  - Gamma-D-glutamylaminomethyl sulfonic acid (GAMS) distinguishes subtypes of
      glutamate receptor in the chick cochlear nucleus (nuc. magnocellularis).
AB  - Because kainic acid (KA) is more potent than other excitatory amino acids (EAAs)
      in affecting synaptic transmission in the cochlear nucleus, previous reports have
      concluded that primary afferent neurotransmission to the cochlear nucleus in
      birds and mammals is mediated by KA-preferring non-N-methyl-D-aspartate (non
      NMDA) EAA receptors. Since this conclusion is at odds with a number of studies
      suggesting that rapid excitatory neurotransmission in the CNS is mediated by
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring non
      NMDA receptors, we re-examined the pharmacology of synaptic transmission between
      the cochlear nerve and nucleus magnocellularis (NM) in chickens, using bath
      application of drugs and recording of field potentials evoked in NM by electrical
      stimulation of the cochlear nerve in vitro. A series of EAA agonists produced
      complete, concentration-dependent and reversible suppression of postsynaptic
      responses: the order of potency was domoic acid (DO) greater than KA greater than
      AMPA much greater than quisqualic acid much greater than L-glutamic acid (Glu).
      Three quinoxalinedione antagonists of non-6-nitro-7-sulphamobenzo[f]quinoxaline
      2,3-dione NMDA receptors also produced complete, concentration-dependent and
      reversible suppression of postsynaptic responses in NM without affecting the
      presynaptic action potential; the half-maximal inhibitory concentrations (IC50's)
      were 2.7 +/- 0.4 microM for 6-nitro-7-sulphamobenzo[f]quinoxaline-2,3-dione
      (NBQX), 5.3 +/- 0.1 microM for 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and
      10.6 +/- 1.2 microM for 6,7-dinitroquinoxaline-2,3-dione (DNQX).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380000
TI  - Surgery for ovarian cancer.
AB  - Surgery is a critical component of the multimodality approach to ovarian cancer.
      Surgery confirms the diagnosis and establishes the stage of disease, especially
      important when the tumor appears to be limited to the ovaries. In advanced
      disease, surgical cytoreduction improves response to chemotherapy and survival.
      Second-look laparotomy provides a means for assessing response to therapy,
      predicting prognosis, and determining the need for further therapy. Surgery can
      also provide palliation of intestinal obstruction.

PMID- 1380001
TI  - Basic fibroblast growth factor-induced activation of latent transforming growth
      factor beta in endothelial cells: regulation of plasminogen activator activity.
AB  - Exposure of bovine aortic or capillary endothelial cells to basic FGF (bFGF) for
      1 h resulted in an approximately sixfold increase in plasminogen activator (PA)
      activity by 18 h that returned nearly to basal levels by 36 h. We hypothesized
      that the decrease in PA activity following bFGF stimulation was mediated by
      transforming growth factor beta (TGF-beta) formed from its inactive precursor.
      Conditioned medium collected from endothelial cells 36 h after a 1-h exposure to
      bFGF, but not control medium, inhibited basal levels of PA activity when
      transferred to confluent monolayers of bovine aortic endothelial cells. Antibody
      to TGF-beta neutralized the inhibitory activity of this conditioned medium,
      indicating that the medium contained active TGF-beta. Northern blot analysis and
      quantitation of acid activatable latent TGF-beta in conditioned medium
      demonstrated that bFGF exposure did not increase the amount of transcription or
      secretion of latent TGF-beta by the endothelial cells. Both aprotinin, an
      inhibitor of plasmin, and anti-urokinase type PA IgG blocked the generation of
      active TGF-beta in cultures exposed to bFGF. These results demonstrated that
      plasmin generated by uPA activity is required for the activation of latent TGF
      beta in endothelial cell cultures treated with bFGF. Activation of TGF-beta by
      endothelial cells exposed to bFGF appears to limit both the degree and duration
      of PA stimulation. Thus, in bFGF-stimulated endothelial cell cultures, PA levels
      are controlled by a negative feedback loop: PA, whose expression is stimulated by
      bFGF, contributes to the formation of TGF-beta, which in turn opposes the effects
      of bFGF by limiting PA synthesis and activity. These studies suggest a role for
      TGF-beta in reversing the invasive stage of angiogenesis and contributing to the
      formation of quiescent capillaries.

PMID- 1380002
TI  - Identification of a peptide sequence involved in homophilic binding in the neural
      cell adhesion molecule NCAM.
AB  - The neural cell adhesion molecule NCAM is capable of mediating cell-cell adhesion
      via homophilic interactions. In this study, three strategies have been combined
      to identify regions of NCAM that participate directly in NCAM-NCAM binding:
      analysis of domain deletion mutations, mapping of epitopes of monoclonal
      antibodies, and use of synthetic peptides to inhibit NCAM activity. Studies on L
      cells transfected with NCAM mutant cDNAs using cell aggregation and NCAM
      covasphere binding assays indicate that the third immunoglobulin-like domain is
      involved in homophilic binding. The epitopes of four monoclonal antibodies that
      have been previously shown to affect cell-cell adhesion mediated by NCAM were
      also mapped to domain 3. Overlapping hexapeptides were synthesized on plastic
      pins and assayed for binding with these monoclonal antibodies. One of them (PP)
      reacted specifically with the sequence KYSFNY. Synthetic oligopeptides containing
      the PP epitope were potent and specific inhibitors of NCAM binding activity. A
      substratum containing immobilized peptide conjugates also exhibited adhesiveness
      for neural retinal cells. Cell attachment was specifically inhibited by peptides
      that contained the PP-epitope and by anti-NCAM univalent antibodies. The shortest
      active peptide has the sequence KYSFNYDGSE, suggesting that this site is directly
      involved in NCAM homophilic interaction.

PMID- 1380003
TI  - CD44H regulates tumor cell migration on hyaluronate-coated substrate.
AB  - CD44 is a broadly distributed cell surface glycoprotein expressed in different
      isoforms in various tissues and cell lines. One of two recently characterized
      human isoforms, CD44H, is a cell surface receptor for hyaluronate, suggesting a
      role in the regulation of cell-cell and cell-substrate interactions as well as of
      cell migration. While CD44H has been shown to mediate cell adhesion, direct
      demonstration that CD44H expression promotes cell motility has been lacking. In
      this work we show that a human melanoma cell line, stably transfected with CD44H,
      displays enhanced motility on hyaluronate-coated surfaces while transfectants
      expressing an isoform that does not bind hyaluronate, CD44E, fail to do so.
      Migration of CD44H-expressing transfectants is observed to be blocked by a
      soluble CD44-immunoglobulin fusion protein as well as by anti-CD44 antibody, and
      to depend on the presence of the cytoplasmic domain of CD44. However, cells
      expressing CD44H cytoplasmic deletion mutants retain significant binding capacity
      to hyaluronate-coated substrate. Taken together, our results provide direct
      evidence that CD44H plays a major role in regulating cell migration on
      hyaluronate-coated substrate.

PMID- 1380004
TI  - Structural and histochemical studies of Golgi complex differentiation in salivary
      gland cells during Drosophila development.
AB  - Morphological alterations in the Golgi complex (GC) and changes in the
      distribution of acid phosphatase (AcPase), thiamine pyrophosphatase (TPPase),
      complex carbohydrates and reduced osmium tetroxide compounds in this organelle
      were studied in the salivary gland cells of Drosophila during larval and prepupal
      development. The morphology and the AcPase, TPPase and complex carbohydrates
      cytochemical patterns of the Golgi complex varied characteristically during cell
      differentiation. At the early 3rd instar period the Golgi complex consisted
      mainly of vesiculated cisternae, and AcPase activity was observed in all
      cisternae but not in the secretory granules. As development proceeded to the late
      3rd instar the Golgi complex displayed its typical appearance, consisting of four
      to six cisternae, and only the two to three cisternae towards the trans-face as
      well as the trans-Golgi network and some of the immature secretory granules
      exhibited AcPase reactivity. In the course of a 'wave' of production of the
      'glue' secretory granules proceeding proximally through the gland, the number of
      AcPase positive cisternae changed correspondingly. After secretion of the 'glue'
      secretory granules, the size of the Golgi complex decreased and almost all
      cisternae displayed AcPase reactivity. The detection of TPPase activity presented
      some specificity problems, since staining was observed not only in the GC
      cisternae but in the endoplasmic reticulum (ER) and microvilli. The reaction
      products were seen in a few GC vesicles during the early 3rd instar and in the
      trans side of the organelle at the end of the 3rd instar. During production of
      the secretory granules, every GC cisterna was intensely stained. These results
      agree with previous findings suggesting that AcPase and TPPase in secretory cells
      may be primarily involved in the processing of exportable proteins. The vicinal
      (vic)-glycol groups of the complex carbohydrates were detected using the periodic
      acid/thiocarbohydrazide/silver proteinate (PA-TCH-SP) technique. During synthesis
      of the 'glue' secretory granules, the reaction products were observed over the GC
      cisternae and the trans-Golgi network, with increasing intensity from the cis to
      the trans side of the organelle. No PA-TCH-SP staining was observed over the GC
      cisternae during the early 3rd instar. Following discharge of the 'glue'
      secretory granules, all GC cisternae displayed uniform PA-TCH-SP staining. After
      OsO4 impregnation, the reaction products were observed mainly in ER and
      mitochondria and rarely in the GC. In numerous cells, only the mitochondria were
      stained, while in many cases the ER of neighboring cells exhibited differential
      staining.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380005
TI  - Determination of protein pattern in embryonic cavities of human early
      pregnancies: a means to understand materno-embryonic exchanges.
AB  - Exocoelomic and amniotic fluids were obtained by selective puncture under
      ultrasound guidance in normal human pregnancies between 5 and 13 weeks of
      gestation. Evaluation of the protein patterns in the exocoelomic fluid showed
      qualitative and quantitative changes with advancing gestation. During the second
      month of gestation, three electrophoretic bands were found with mobility
      compatible with albumin, alpha 1-globulin and beta-globulin and composed of at
      least eight proteins including: pre-albumin, albumin, alpha-fetoprotein (alpha
      FP), alpha 1-protease inhibitor, haptoglobin, ceruloplasmin, transferrin and
      immunoglobulin-G, as revealed by immunoblotting. Protein patterns obtained
      between 9 and 13 weeks were comparable in exocoelomic fluid and in maternal serum
      except for the presence of alpha-FP in the alpha 1-globulin band. At the same
      gestational age, protein electrophoresis of amniotic fluid revealed four bands
      corresponding to albumin, alpha-FP, haptoglobin and transferrin. Creatinine
      levels were significantly lower (P less than 0.01) in amniotic fluid than in
      exocoelomic fluid, and alpha-FP levels were similar in both exocoelomic and
      amniotic fluids. These results suggest that the exocoelomic fluid is a transudate
      of the maternal serum except for the presence of high levels of alpha-FP, that
      amniotic and exocoelomic cavities are separated by a non-permeable membrane and
      that the secondary yolk sac plays an important role in early protein synthesis
      and transfer.

PMID- 1380006
TI  - The use of fibrin sealant for embryo transfer: development and clinical studies.
AB  - Many embryo transfers after in-vitro fertilization may fail because of expulsion
      of the embryos from the uterus. Approximately 5-8% of pregnancies resulting from
      embryo transfer are ectopic. The aim of our study was to find a technique to
      avoid ectopic pregnancies and to improve the pregnancy rate. We used a two
      component fibrin sealant which also contains a fibrinolysis inhibitor (aprotinin)
      at various concentrations. After gaining experience with mouse embryos, the
      sealant was used in human embryo transfer with great success. The results of a
      pilot study encouraged us to perform a prospective randomized study on 546
      patients (270 with fibrin sealant, 276 conventional embryo transfers). There were
      47 (17.0%) orthotopic pregnancies and 6 (2.2%) ectopic pregnancies in the control
      group, whereas there were 51 (18.9%) intrauterine and no ectopic pregnancies in
      the treatment group. The difference in ectopic pregnancies was statistically
      significant (P less than 0.05). With regard to the aprotinin concentration, there
      was a trend towards better results with 100-150 kIU (28.5% clinical pregnancies)
      in comparison to 250-300 kIU (19.2%) or no aprotinin (20.4%) (not significant).
      Further improvements of the technique may raise the pregnancy rate when fibrin
      sealant is used. As shown in our prospective randomized study, ectopic
      pregnancies may be completely avoided.

PMID- 1380007
TI  - Immunodominant regions within the hepatitis C virus core and putative matrix
      proteins.
AB  - The complete amino acid sequences of hepatitis C virus (HCV) core (residues 1 to
      115) and putative matrix (residues 116 to 190) proteins were synthesized as 18
      residue-long peptides with an 8-amino-acid overlap. The peptides were assayed
      with 50 human serum samples with antibodies to HCV (anti-HCV) and 46 serum
      samples without anti-HCV, as determined by several commercial assays.
      Immunodominant regions were defined within residues 1 to 18, 11 to 28, 21 to 38,
      51 to 68, and 101 to 118. The peptides that covered these regions were recognized
      by 40 of 50 (80%), 42 of 50 (84%), 36 of 50 (72%), 34 of 48 (68%), and 36 of 48
      (72%) of the anti-HCV positive serum samples, respectively. Two anti-HCV negative
      serum samples were each repeatedly reactive with one peptide, but both were found
      to be negative by confirmatory anti-HCV assays. Four serum samples that were
      confirmed to be positive for anti-HCV in commercial assays did not recognize any
      of the peptides that cover the HCV core-matrix regions. Ninety-two percent of
      anti-HCV-positive serum samples reacted with a combination of peptides covering
      residues 1 to 18 and 11 to 28. Testing of peptides that contain the reported
      genotypic variations of the HCV core within the regions at residues 1 to 18, 51
      to 68, and 101 to 118 showed that a change from Thr-110 to Asn-110 decreased the
      reactivities of eight serum samples. In conclusion, we found that human
      antibodies to the HCV core-matrix protein(s) are mainly directed to linear
      determinants and can easily be reproduced by using short synthetic peptides. We
      also found that such antibodies develop in more than 90% of HCV-infected people.

PMID- 1380008
TI  - Rapid identification of fibronectin, vitronectin, laminin, and collagen cell
      surface binding proteins on coagulase-negative staphylococci by particle
      agglutination assays.
AB  - Seventeen strains of ten different species of coagulase-negative staphylococci
      were shown to interact with collagen, laminin, fibronectin, and vitronectin
      immobilized on latex beads. Different species of coagulase-negative staphylococci
      have different capacities to agglutinate proteins. Cells of 18 strains of
      Staphylococcus haemolyticus reacted more strongly than did cells of 18
      Staphylococcus epidermidis strains with proteincoated latex beads, although no
      significant difference in cell surface hydrophobicity or charge could be shown.
      The cell surface receptors of S. haemolyticus were more heat and protease
      resistant than were Staphylococcus aureus receptors. Strains of Staphylococcus
      saprophyticus isolated from urinary tract infections showed a high capacity to
      adhere to laminin. The ability to agglutinate fibronectin and collagen was common
      among coagulase-negative staphylococci isolated from other infections; 55% (31 of
      56) and 63% (35 of 56) agglutinated fibronectin and/or collagen. S. haemolyticus
      and S. epidermidis bound to both N-terminal (29-kDa) and C-terminal (120-kDa)
      fragments of fibronectin.

PMID- 1380009
TI  - Production and characterization of monoclonal antibodies to type 8
      lipooligosaccharide of Neisseria meningitidis.
AB  - Eight monoclonal antibodies (MAbs) to lipooligosaccharides (LOSs) of Neisseria
      meningitidis were produced by immunizing mice with purified LOS from group A
      meningococcal strain A1. The specificities of the MAbs were examined by enzyme
      linked immunosorbent assay (ELISA), immunodot assay, and ELISA inhibition by
      using the homologous A1 LOS, 12 immunotype LOSs of N. meningitidis (L1 through
      L12), and LOSs or lipopolysaccharides from other gram-negative bacteria. Two of
      the MAbs, 4385G7 (immunoglobulin G2b [IgG2b]) and 4387A5 (IgG2a), had the
      strongest reactivities with the homologous A1 LOS, moderate reactivities with the
      M978 (L8) LOS, but no reactivity with other LOSs. The other six MAbs (4 IgM and 2
      IgG3) reacted with the A1 LOS and with several or many of the 12 LOSs. ELISA
      inhibition at 50% showed that the inhibitory activities of the LOSs from strains
      A1 and BB431 (a group B strain) to the specific MAb 4387A5 were about 10 to 20
      times greater than that of the M978 (L8) LOS. When compared with MAb 2-1-L8 (L8)
      by Western blot (immunoblot) analysis and ELISA inhibition, the two specific MAbs
      recognized a different epitope in the 3.6-kDa LOSs of strains A1 and BB431. We
      propose that the new epitope is L8a, since the MAbs also reacted with the M978
      (L8) LOS. The expression of the L8a epitope in the A1 LOS requires a few
      monosaccharide residues in its oligosaccharide moiety, and the fatty acid
      residues in its lipid A moiety also play a role. In a whole-cell ELISA, the two
      specific MAbs bound specifically to the homologous strain A1 and the L8 prototype
      strain M978 but not to any other LOS prototype strains. These results suggest
      that the two specific MAbs can be used for LOS typing of N. meningitidis.

PMID- 1380010
TI  - Molecular epidemiology of Pseudomonas cepacia determined by polymerase chain
      reaction ribotyping.
AB  - Traditional ribotyping detects genomic restriction fragment length polymorphisms
      by probing chromosomal DNA with rRNA. Although it is a powerful method for
      determining the molecular epidemiology of bacterial pathogens, technical
      difficulties limit its application. As an alternative, polymorphisms were sought
      in the 16S-23S spacer regions of bacterial rRNA genes by use of the polymerase
      chain reaction (PCR). Chromosomal DNA from isolates of Pseudomonas cepacia was
      used as a template in the PCR with oligonucleotide primers complementary to
      highly conserved sequences flanking the spacer regions of the rRNA genes. Length
      polymorphisms in the amplified DNA distinguished unrelated isolates of P.
      cepacia. Isolates of P. cepacia previously implicated in person-to-person
      transmission were shown to have identical amplification patterns. These data
      demonstrate the utility of this new PCR ribotyping method for determining the
      molecular epidemiology of bacterial species.

PMID- 1380011
TI  - Development of a polymerase chain reaction-probe test for identification of
      Alloiococcus otitis.
AB  - A rapid polymerase chain reaction test was developed for specific identification
      of the human middle ear pathogen Alloiococcus otitis. Primers for the enzymatic
      amplification reaction were designed from highly specific sequences within the
      16S rRNA gene. In addition, a confirmatory test based on hybridization of the
      polymerase chain reaction products to a specific internal probe was developed.

PMID- 1380012
TI  - Cortical afferents to behaviorally defined regions of the inferior temporal and
      parahippocampal gyri as demonstrated by WGA-HRP.
AB  - The inferior temporal gyrus in the monkey appears to be unique among the many
      extrastriate visual cortices in its importance for normal performance of delayed
      match-to-sample, a visual memory task. However, the anatomical pathway providing
      visual information to this portion of the temporal lobe remains unclear. In this
      study, wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was
      injected into the anterior inferior temporal gyrus and heavy projections were
      found to arise in cytoarchitectural area TF of the parahippocampal gyrus, as well
      as moderate projections in more posterior portions of inferior temporal gyrus and
      perirhinal and entorhinal cortices. Subsequently, WGA-HRP was injected into area
      TF, resulting in retrogradely labeled cells primarily located in the portions of
      area TF adjacent to the injection and also in the occipitotemporal sulcus
      including the ventral portion of the prestriate visual area V4. Moderate
      projections were found to originate from the dorsal region of area V4 in the
      lunate sulcus, portions of the caudal parietal lobe, the posterior bank of caudal
      superior temporal sulcus, and area OPT located at the tip of the superior
      temporal sulcus. The middle temporal gyrus, foveal prestriate cortex, and area
      TEO, a transitional area between temporal and occipital visual areas, were all
      free from retrogradely labeled cells. These latter areas are included in the well
      established anatomical system that is known to carry visual information from
      striate cortex through prestriate to eventually reach dorsal portions of
      inferotemporal cortex which is coincident with the temporal lobe visual area TE.
      It is suggested here that there is an additional ventral pathway into area TE as
      well, which includes projections through portions of the prestriate cortex,
      occipitotemporal sulcus, and parahippocampal gyrus, ultimately reaching the
      anterior inferior temporal gyrus, an area that may be specialized to hold visual
      information over brief periods of time.

PMID- 1380013
TI  - Retinal growth and cell addition during embryogenesis in the teleost,
      Haplochromis burtoni.
AB  - Neurogenesis of the developing embryonic retina is described for the African
      cichlid fish, Haplochromis burtoni, from 4 days post fertilization until all cell
      phenotypes are generated (day 7). Cell addition and differentiation both begin at
      the same absolute location which later becomes the central retina. As observed in
      most other vertebrates, cones and ganglion cells differentiate first, followed by
      amacrine and bipolar cells. Rod photoreceptors, which are added late,
      differentiate last. Changes in retinal thickness, retinal stretching, cell size,
      and cell density were measured during development. From day 4 through 7, there is
      an increase in retinal thickness largely due to the expansion of the inner
      plexiform layer (IPL) and outer nuclear layer (ONL). The inner nuclear layer
      (INL) decreases in thickness and there is a transient decrease in the density of
      cells in the scleral portion of the INL. Cells increase in size in the ganglion
      cell layer (GCL) and the vitread INL, decrease in size in the sclerad INL, and
      remain the same in the ONL. Changes in the density of the cell layers were
      observed: the density of ONL cells increased, the density of GCL cells decreased,
      and INL cells increased then decreased. From day 4 to day 6, eye growth is
      entirely due to cell addition because no retinal stretching was observed in the
      ONL or the horizontal layer. During this same developmental period, the pattern
      and rate of neurogenesis were measured in the differentiated portion of the
      retina by means of 3H-thymidine labeling. A small number of cell divisions within
      the differentiated INL precede the onset of cell divisions in the ONL. The number
      of 3H-thymidine labeled cells within the INL increases at a low rate consistent
      with an asymmetric pattern of cell division characteristic of stem cells. In
      contrast, cell divisions in the ONL increase exponentially, consistent with a
      symmetric pattern of cell division characteristic of progenitor cells. Double
      label experiments (3H-thymidine and a rod specific opsin antibody) show that some
      of the symmetrically dividing cells in the ONL express the rod specific opsin
      within 2 days, suggesting that these dividing cells are rod progenitors. Although
      we do not hae conclusive evidence, these developmental processes support the
      hypothesis that stem cells within the INL could be the source of rod precursors
      in the embryonic teleost retina.

PMID- 1380014
TI  - NADPH diaphorase in the spinal cord of rats.
AB  - To identify spinal neurons that may synthesize nitric oxide, cells and fibers
      histochemically stained for NADPH diaphorase (a nitric oxide synthase) were
      studied in the spinal cord of rats. The histochemical reaction gave an image
      similar to the best Golgi impregnations, staining cells down to their finest
      processes. Transverse, horizontal, and parasagittal 50 and 100 microns sections
      were used to follow dendritic and axonal arborizations of stained neurons. Major
      cell groups were identified in the superficial dorsal horn and around the central
      canal (at all spinal levels), and in the intermediolateral cell column (at
      thoracic and sacral levels). Scattered positive cells were also found in deeper
      dorsal horn, ventral horn, and white matter. In some cases, axons of cells in the
      dorsal horn could be traced into the white matter; many of these cells resembled
      neurons projecting to various supraspinal targets. Stained cells in the
      intermediolateral column, which sent their axons into the ventral root, were
      presumed to be preganglionic autonomic neurons. Dense plexes of fibers were
      stained in laminae I and II and in the intermediolateral column. A large number
      of NADPH diaphorase-positive neurons in the spinal cord appear to be involved in
      visceral regulation. Fibers of the intermediolateral system had a special
      relationship with vasculature, suggesting that nitric oxide may help to couple
      neural activity with regional blood flow in the spinal cord. The abundance of
      NADPH diaphorase-positive neurons and fibers in the superficial dorsal horn
      suggests that nitric oxide may also be involved in spinal sensory processing.

PMID- 1380015
TI  - Afferent projections to the mammillary complex of the rat, with special reference
      to those from surrounding hypothalamic regions.
AB  - To better understand the functional organization of the mammillary nuclei, we
      investigated the afferents to this nuclear complex in the rat with
      iontophoretically injected wheat germ agglutinin conjugated to horseradish
      peroxidase. Particular attention was paid to tracing local hypothalamic afferents
      to these nuclei. Injections into the medial mammillary nucleus (MMN) revealed
      strong projections from the subicular region, and weaker projections from the
      prefrontal cortex, medial septum, and the nucleus of the diagonal band of Broca.
      Other descending subcortical projections to the MMN arise from the anterior and
      the lateral hypothalamic area, the medial preoptic area, and the bed nucleus of
      the stria terminalis. Ascending afferents to the MMN were found to originate in
      the raphe and various tegmental nuclei. Following all injections into the MMN,
      labelled neurons were found in nuclei surrounding the mammillary body. The
      lateral and posterior subdivisions of the tuberomammillary nucleus projected
      mainly to the pars medianus and pars medialis of the MMN. The dorsal and ventral
      premammillary nuclei projected to the pars lateralis of the MMN. The
      supramammillary nucleus at rostral level had a small projection to the pars
      medialis and lateralis of the MMN. However, the most obvious projection from this
      nucleus was to the pars posterior of the MMN, chiefly from the lateral part of
      the caudal supramammillary nucleus. Injections into the lateral mammillary
      nucleus revealed inputs from the presubiculum, parasubiculum, septal region,
      dorsal tegmental nucleus, dorsal raphe nucleus, and periaqueductal gray. In
      addition, the lateral mammillary nucleus was found to receive a moderate
      projection from the medial part of the supramammillary nucleus and stronger
      projections from the lateral part of the caudal supramammillary nucleus. A very
      light projection was also seen from the lateral and posterior subdivisions of the
      tuberomammillary nucleus. These findings add to our knowledge of the extensive
      and complex connectivity of the mammillary nuclei. In particular, the local
      connections we have demonstrated with the supramammillary and tuberomammillary
      nuclei indicate the existence of significant local circuits as well as circuits
      involving more distant brain regions such as the septal nuclei, subiculum,
      prefrontal cortex, and brain stem tegmentum.

PMID- 1380016
TI  - A dopaminergic projection to the rat mammillary nuclei demonstrated by retrograde
      transport of wheat germ agglutinin-horseradish peroxidase and tyrosine
      hydroxylase immunohistochemistry.
AB  - The presence and distribution of dopaminergic neurons and terminals in the
      hypothalamus of the rat were studied by tyrosine hydroxylase (TH)
      immunohistochemistry. Strongly labelled TH-immunoreactive neurons were seen in
      the dorsomedial hypothalamic nucleus, periventricular region, zona incerta,
      arcuate nucleus, and supramammillary nucleus. A few TH-positive neurons were also
      identified in the dorsal and ventral premammillary nucleus, as well as the
      lateral hypothalamic area. TH-immunoreactive fibres and terminals were unevenly
      distributed in the mammillary nuclei; small, weakly labelled terminals were
      scattered in the medial mammillary nucleus, while large, strongly labelled,
      varicose terminals were densely concentrated in the internal part of the lateral
      mammillary nucleus. A few dorsoventrally oriented TH-positive axon bundles were
      also identified in the lateral mammillary nucleus. A dopaminergic projection to
      the mammillary nuclei from the supramammillary nucleus and lateral hypothalamic
      area was identified by double labelling with retrograde transport of wheat germ
      agglutinin-horseradish peroxidase and TH-immunohistochemistry. The lateral
      mammillary nucleus receives a weak dopaminergic projection from the medial, and
      stronger projections from the lateral, caudal supramammillary nucleus. The double
      labelled neurons in the lateral supramammillary nucleus appear to encapsulate the
      caudal end of the mammillary nuclei. The medial mammillary nucleus receives a
      very light dopaminergic projection from the caudal lateral hypothalamic area.
      These results suggest that the supramammillary nucleus is the principal source of
      the dopaminergic input to the mammillary nuclei, establishing a local TH-pathway
      in the mammillary complex. The supramammillary cell groups are able to modulate
      the limbic system through its dopaminergic input to the mammillary nuclei as well
      as through its extensive dopaminergic projection to the lateral septal nucleus.

PMID- 1380017
TI  - Effect of clinical and subclinical mastitis on lipid composition of teat canal
      keratin.
AB  - Two experiments were conducted to investigate lipid composition of teat canal
      keratin when different conditions of bacterial colonization and quarter
      inflammation were present. In Experiment 1, 11 multiparous cows with subclinical
      mastitis (bacteria present but no visible inflammation) in at least one quarter
      were selected for study. Quarters that were sampled and found negative for
      bacterial growth were classified as control. In Experiment 2, 10 multiparous cows
      with clinical mastitis in one or more quarters were selected. Milk samples from
      inflamed quarters were cultured to identify mastitis pathogens; these quarters
      were classified as clinical; all other quarters were classified as control. Teat
      canal keratin was collected from all quarters just before an a.m. milking,
      samples were weighed, and lipid determinations were conducted by TLC. Keratin
      from subclinical quarters compared with keratin from control quarters did not
      differ in either neutral lipid or fatty acid composition. Total lipid was
      significantly higher in keratin from teats of clinical quarters than in keratin
      from control quarters (27.8 vs. 21.5 microgram/mg). Neutral lipid composition of
      keratin was similar between teats from clinical quarters and teats from control
      quarters. In Experiment 2, quarter foremilk samples were also obtained to
      determine lipid composition. The FFA in milk from clinical quarters contained
      fewer short-chain fatty acids, whereas polyunsaturated fatty acids were
      significantly higher in milk from clinical quarters.

PMID- 1380018
TI  - The effect of inhaled allergen on circulating basophils in atopic asthma.
AB  - There is increasing evidence for the role of basophils in the allergen-induced
      late asthmatic response (LAR). To study the effect of inhaled allergen on
      basophil function in subjects with asthma, ex vivo basophil spontaneous histamine
      release (SHR) in peripheral blood and plasma histamine was measured before and 2,
      5, 10, and 15 minutes, and 2, 4, 6, and 8 hours after allergen bronchial
      challenge (allergen study day) in six subjects with atopic asthma. Allergen
      inhalation induced an early response and LAR consisting of a mean (+/- SD) 32.5%
      (+/- 7.9%) and 28.8% (+/- 7.7%) fall in FEV1, respectively. As a control for the
      effects of bronchoconstriction, on another occasion, methacholine challenge was
      performed to produce a mean 33.4% (+/- 3.4%) fall in FEV1 during the early
      response and no LAR, and blood was obtained to measure basophil histamine release
      (HR) and plasma histamine. There was a small, but significant (p less than 0.05),
      rise in median SHR from 4.6% to 6.1% of total basophil histamine after allergen
      but not after methacholine inhalation. HR remained high after allergen inhalation
      during the 8 hours of study, whereas it demonstrated a steady, significant,
      decrease between 4 to 8 hours after methacholine inhalation. No significant
      changes in plasma histamine were recorded on either allergen or methacholine
      study days. On a third occasion, SHR was measured after challenge with
      physiologic saline to control for any effects of methacholine on SHR, and a
      decrease in HR was recorded during the day similar to HR observed after
      methacholine challenge. These studies suggest an enhancing effect of inhaled
      allergen on SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380019
TI  - Skin-derived aeroallergen-specific T-cell clones of Th2 phenotype in patients
      with atopic dermatitis.
AB  - T-cell lines have been derived from aeroallergen-induced eczematous patch test
      sites of patients with atopic dermatitis (AD). Biopsy specimens were obtained 24
      hours after allergen application to the skin, and only in vivo-activated T cells
      were propagated. From one patient, the T-cell lines were subcloned at 0.3 cells
      per well. With allergen-induced interleukin (IL) production, all clones tested (n
      = 13) were found to be specific for the allergen, producing IL-4 and granulocyte
      macrophage-colony-stimulating factor. No IL-2 or interferon-gamma was found. The
      allergen-specific proliferative response of these clones, although the response
      was dependent on exogenous IL-2 or IL-4, also proved that all clones were
      allergen specific. Under optimal stimulation (aCD3 plus phorbol myristate
      acetate), 15% of the clones appeared to be of Th0 phenotype and 70% of Th2
      phenotype. In 15% of the clones, IL-4 was produced in the absence of IL-2, IL-5,
      or interferon-gamma. Supernatants of all clones tested induced IgE production by
      B cells from normal non-atopic donors. The T-cell lines of the other patient
      demonstrated similar results; allergen-specific proliferation was dependent on
      exogenous IL-2 or IL-4 and stimulation with aCD3 plus phorbol myristate acetate
      demonstrated that the T cells in these lines were of the Th2 phenotype. In
      conclusion, our data reveal that, in AD, percutaneous sensitization to
      aeroallergens may occur and indicate that allergen-specific Th2 type T cells may
      be responsible for the high levels of (specific) IgE found in 80% of patients
      with AD.

PMID- 1380020
TI  - Chronic Pneumocystis carinii infection of the liver. A case report and review of
      the literature.
AB  - Pneumocystis carinii infection of the liver is being reported with increasing
      frequency in patients with acquired immune deficiency syndrome (AIDS). The
      clinical picture typically resembles hepatitis. We report such an occurrence in a
      patient with persistent elevation of alkaline phosphatase and gamma-glutamyl
      transpeptidase with relatively normal transaminases who was found to have P.
      carinii on antemortem liver biopsy. The differential diagnosis of abnormal
      alkaline phosphatase and gamma-glutamyl transpeptidase in patients with AIDS
      should include P. carinii.

PMID- 1380021
TI  - Anti-HCV positive hepatocellular carcinoma in cirrhosis. Prevalence, risk factors
      and clinical features.
AB  - Recent reports indicate that hepatitis C virus (HCV) may play a role in the
      pathogenesis of hepatocellular carcinoma in cirrhotics. Using an ELISA test, we
      evaluated the prevalence of anti-HCV antibodies in 97 patients with
      hepatocellular carcinoma (HCC) in cirrhosis and in a group of 223 patients,
      including: 49 patients with HBsAg-positive chronic liver disease (CLD), 42 with
      alcoholic CLD, 110 with cryptogenic CLD and 22 with post-transfusional HBsAg
      negative CLD. All diagnoses were histologically confirmed. Overall, anti-HCV
      positive HCC were 64% of the total, with no statistically significant difference
      with respect to CLD (60.9%). The prevalence of anti-HCV was higher in cryptogenic
      HCC (80%) than in HBsAg-positive (60%) or alcoholic HCC (42.8%) (p less than
      0.005). When HCC and cirrhosis of similar putative etiology were considered, anti
      HCV prevalence was significantly higher in HCC than in cirrhosis only in the
      groups of patients with alcoholic liver damage (60% in HCC vs. 38% in cirrhosis,
      p less than 0.005). In HBsAg-positive patients, anti-HCV prevalence was twice as
      high in HCC than in CLD, but the difference was not statistically significant.
      Overall, anti-HCV prevalence in HCC was significantly higher than in alcoholic or
      HBsAg-positive CLD (p less than 0.001 and p less than 0.01, respectively) but
      lower than in cryptogenic CLD (p less than 0.001). Association between anti-HCV
      and anti-HBc was significantly more prevalent in patients with CLD than in those
      with HCC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380022
TI  - Cytokeratin of apparent high molecular weight in livers from griseofulvin-fed
      mice.
AB  - Livers from mice fed griseofulvin (GF) for 12 months contain abnormal cytokeratin
      (CK) intermediate filaments (IFs) that aggregate to form Mallory bodies (MBs).
      Sections from control and GF-treated livers were extracted with Triton X-100. IF
      enriched fractions were analyzed by gel electrophoresis and IF proteins were
      identified by Western blotting using anti-CK 55 (TROMA 1) and CK 49 (TROMA 2),
      and the anti-'universal' IF known as aIF. Western blotting on control and GF
      treated livers with TROMA 1 and TROMA 2 obtained with gels loaded with 2
      micrograms of protein revealed the presence of CK 55 and CK 49. In contrast, when
      a larger amount of protein was loaded on the gel (10 or 12 micrograms) the
      results were different. In the control we detected bands corresponding to CK 55
      and CK 49 plus a faint band at approx. 97 kDa. In the GF-treated animals, we
      detected a more pronounced reaction with the 97 kDa band and in addition we now
      detected several higher molecular weight bands which reacted with anti-CK
      antibodies. These results demonstrated that the induced changes in CKs in the GF
      liver are associated with the increase of apparent high molecular weight CK.
      These apparent high molecular weight CKs could be obtained by a pathological
      cross-linking of the preexisting liver CK monomers in different combinations such
      as CK 55-55, CK 49-49 and/or with other proteins.

PMID- 1380023
TI  - Increased transforming growth factor-beta 1 gene expression in human liver
      disease.
AB  - We recently demonstrated that transforming growth factor-beta 1 stimulates
      collagen synthesis in hepatic cells in vitro, and that the synthesis of this
      cytokine is markedly increased in two rodent models of hepatic fibrosis. In the
      present study, we investigated the association of transforming growth factor-beta
      1 (TFG-beta 1) gene expression in human liver disease. Sixteen patients with
      active liver disease had percutaneous liver biopsies performed for diagnostic
      purposes. Total RNA was extracted from an unused portion of each biopsy and then
      subjected to hybridization analysis with the following human cDNA clones:
      albumin, pro alpha 1 (I) collagen, and TGF-beta 1. Surgical liver biopsy
      specimens from two patients without hepatic disease were used as controls. When
      compared to controls, the patients with active liver disease had a 19% decrease
      in albumin, a 97% increase in type I collagen, and a 120% increase in
      transforming growth factor-beta 1 mRNA levels. Moreover, steady-state levels of
      TGF-beta 1 and procollagen mRNAs were significantly correlated. Nuclear run-on
      assays showed that livers from two patients with fibrosis had TGF-beta 1
      transcription rates that were more than 2-fold higher than rates in control
      livers. These findings indicate that transforming growth factor-beta 1 gene
      expression is significantly enhanced in man during active liver disease.

PMID- 1380024
TI  - Paracentesis with Dextran 70 vs. paracentesis with albumin in cirrhosis with
      tense ascites. Results of a randomized study.
AB  - Forty-one patients with cirrhosis and tense ascites were randomized to receive
      daily paracentesis of 5 liters associated with Dextran 70 as volume expander (6 g
      for each 1000 ml of ascites removed) (group I = 20 patients) or paracentesis with
      albumin (6 g for each 1000 ml of ascites) (group II = 21 patients). The basal
      clinical features, laboratory data, and plasma renin activity were similar in
      both groups. The volume of ascites removed was 12.9 +/- 4.4 and 10.9 +/- 3.7
      liters in group I and II, respectively (n.s.). No significant changes were
      observed in liver and renal function tests, KPTT, platelet count, factor VIII,
      serum electrolytes or plasma renin activity 24 and 96 h after the last
      paracentesis in both groups, except for a decrease in bilirubin in group I and a
      transient increase of serum albumin in group II. Four patients developed
      complications in each group, mainly hyponatremia, while one patient in each group
      developed renal impairment. One patient from group I died with hepatic
      encephalopathy. Moreover, the probability of survival and readmission to the
      hospital because of tense ascites were similar in both groups of patients during
      the follow-up. The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30
      dollars with albumin for each patient treated. These results indicate that
      repeated large volume paracentesis associated with Dextran 70 is as effective and
      safe as paracentesis associated with albumin in cirrhotic patients with tense
      ascites. However, due to its reduced cost, paracentesis with Dextran 70 may be
      considered the treatment of choice in cirrhotic patients with tense ascites
      without liver cancer and renal failure.

PMID- 1380025
TI  - Serological response and detection of viraemia in acute hepatitis C virus
      infection.
AB  - The serological response during acute hepatitis C virus (HCV) infection was
      examined by enzyme-linked immunosorbent assay (ELISA) in sequential serum samples
      from 13 haemophiliacs following their first exposure to factor VIII concentrates
      contaminated with HCV. The commercially available C100-3 peptide and a new 22 kDa
      recombinant protein (p22) encoded by the nucleocapsid region of the viral genome
      were used for antibody detection, whilst a nested polymerase chain reaction (PCR)
      method was used for the detection of viraemia. In addition, eight sporadic cases
      of acute HCV infection were studied. The results in haemophiliacs demonstrated
      that seroconversion to the C100-3 antigen occurred in only one-third of the
      patients within 12 weeks of disease onset, but all of the patients had a
      diagnostic serological response to p22 during this phase of the disease. The new
      test was positive in all the sporadic cases at a time when the commercially
      available test was negative. Although PCR offers a sensitive method for the
      detection of recent HCV infection, the complex methodology makes it unsuitable
      for diagnostic laboratories. The new ELISA test with p22 may therefore have a
      useful diagnostic role in acute disease.

PMID- 1380026
TI  - c-erbB-2 oncogene expression in hepatocellular carcinoma and cholangiocarcinoma.
AB  - The c-erbB-2 proto-oncogene encodes a transmembrane protein which is homologous
      to the epidermal growth factor receptor. This protein can be localized
      immunohistochemically in formalin-fixed paraffin-embedded material using a
      monoclonal antibody NCL-CB11; positive membrane staining correlates with gene
      amplification and protein overexpression in breast cancer. Using this technique
      we have shown that only 2/26 (8%) of hepatocellular carcinomas, 0/10 (0%) of
      cholangiocarcinomas and 0/2 (0%) hepatoblastomas overexpressed c-erbB-2 as
      evidenced by membrane staining. Moreover c-erbB-2 mRNA was not detected in seven
      hepatocellular carcinomas examined by Northern blot analysis. c-erbB-2
      overexpression is, therefore, unlikely to be contributing to the malignant
      phenotype in hepatocellular carcinoma and cholangiocarcinoma.

PMID- 1380027
TI  - Hepatitis C viremia and anti-HCV antibodies in alcoholics.
AB  - We determined serum hepatitis C status using a RIBA2 kit and a sensitive PCR
      procedure in 62 chronic alcoholics, 36 of whom had anti-HCV antibodies (Ab)
      detectable in an ELISA1 assay. Anti-HCV antibodies were detected in 22 patients
      using RIBA2. HCV RNA was detected by means of PCR in 18 patients who were RIBA2
      positive and in none who were RIBA2 negative. Liver biopsies, available for 12
      HCV RNA-positive patients, revealed histological features of purely alcohol
      related lesions in seven and mixed alcohol-viral lesions in five. These results
      indicate that HCV replication is maintained in most alcoholics who score positive
      for anti-HCV Ab in the RIBA2 test, and that HCV viremia can be associated with
      histological features typical of alcoholic liver disease.

PMID- 1380028
TI  - Low rate of hepatitis C virus (HCV) transmission within the family.

PMID- 1380029
TI  - Hepatocellular carcinoma. Frequency of diffuse inhomogenous forms in
      ultrasonography and comparative value of alphafetoprotein and ultrasonically
      guided fine needle aspiration biopsy.

PMID- 1380030
TI  - Prevalence of hepatitis C virus among non-A, non-B-related chronic liver disease
      in Egypt.

PMID- 1380031
TI  - Involvement of CD28 in MHC-unrestricted cytotoxicity mediated by a human natural
      killer leukemia cell line.
AB  - NK cells and certain CTL can recognize and lyse targets without restriction by
      the MHC. NK cells do not express CD3/TCR complexes and the membrane receptors
      participating in MHC-unrestricted cytotoxicity are largely unknown. We
      demonstrate that YT2C2, a human NK leukemia cell line, expresses the CD28
      differentiation Ag and can spontaneously lyse both murine and human cell lines
      expressing B7, a B cell- activation Ag that is a ligand for CD28. The
      participation of CD28/B7 interactions in MHC-unrestricted cytotoxicity mediated
      by YT2C2 cells was demonstrated by correlation of target sensitivity with levels
      of B7 expression, inhibition of cytotoxicity by anti-CD28 or anti-B7 mAb, and by
      making both murine and human cell lines susceptible to YT2C2-mediated lysis by
      genetic transfection with expression vectors containing B7 cDNA. However, CD28/B7
      interactions alone were insufficient to initiate cytotoxicity. mAb inhibition
      experiments and selection of CD54- (intercellular adhesion molecule-1) deficient
      B cell targets indicated that CD11a/18 (lymphocyte function-associated Ag-1) also
      cooperated in CD28/B7-dependent cytotoxicity. The requirement for both CD28/B7
      and lymphocyte function-associated Ag-1/intercellular adhesion molecule-1
      interactions in YT2C2-mediated MHC-unrestricted cytotoxicity was confirmed by
      demonstrating that efficient lysis of murine L cells required cotransfection with
      both B7 and intercellular adhesion molecule-1. These findings support the concept
      that MHC-unrestricted cytotoxicity may not be due to a unique receptor, but may
      result from interactions between an appropriate array of "adhesion" molecules
      with their ligands.

PMID- 1380032
TI  - Differential function of intestinal intraepithelial lymphocyte subsets.
AB  - It has been proposed that intestinal intraepithelial lymphocytes (I-IEL) perform
      immune surveillance of the epithelial layer (1) and regulate mucosal humoral
      responses to exogenous Ag (2). To better understand the functional potential of
      this unique population, purified murine I-IEL were analyzed phenotypically and
      functionally. Initial studies determined that I-IEL could be distinguished based
      on several phenotypic characteristics including: TCR (TCR-alpha beta vs TCR-gamma
      delta); Thy-1, CD45R/B220, CD5, and CD8 (CD8 alpha alpha vs CD8 alpha beta)
      expression. Using anti-TCR mAb, individual I-IEL subsets were activated and
      examined functionally. Both TCR-alpha beta and TCR-gamma delta I-IEL were found
      to synthesize an array of lymphokines that included IL-2, IL-3, and IL-6 but not
      IL-4 or IL-5. Additionally, a number of lymphokines were detected that directly
      influence epithelial function (IFN-gamma, TNF-alpha, and TGF-beta 1). However,
      the majority of the I-IEL function was localized within the Thy-1+, CD45R/B220- I
      IEL subset. In addition those TCR-alpha beta I-IEL expressing the CD8 alpha beta
      heterodimer were more easily activated. Thus, a subset of I-IEL have the capacity
      to respond to TCR-mediated stimuli. The functional activities of these cells may
      influence both local immune cell populations as well as epithelial
      differentiation.

PMID- 1380033
TI  - Restoration of T cell receptor-mediated signal transduction by transfection of
      CD45 cDNA into a CD45-deficient variant of the Jurkat T cell line.
AB  - The TCR is a multimeric structure comprised of distinct Ag recognition and signal
      transduction components. Although none of the molecules that make up the TCR
      possess intrinsic protein tyrosine kinase (PTK) activity, stimulation of T cells
      via the TCR results in the rapid appearance of newly tyrosine phosphorylated
      proteins in cell lysates. Evidence suggests ligation of the TCR induces
      activation of a PTK that may be a member of the src family. One early consequence
      of this TCR-mediated PTK activation is the phosphorylation of the gamma 1 isoform
      of phospholipase C. This phosphorylation event is associated with increased
      enzymatic activity resulting in the hydrolysis of phosphatidylinositol 4,5
      bisphosphate into two second messengers, inositol 1,4,5 trisphosphate and
      diacylglycerol. Recently, our laboratory and others have isolated mutant T cells
      that lack surface expression of CD45, the major surface tyrosine phosphatase
      expressed on lymphoid cells. Stimulation of the TCR on these cells fails to
      result in the expected activation events. We demonstrate that reconstitution of
      surface expression of the 180-kDa isoform of CD45 by gene transfer into a CD45
      deficient mutant of the Jurkat T cell leukemic line restores the ability of the
      TCR to couple fully to its signal transduction machinery. These results support
      the role of CD45 tyrosine phosphatase activity in regulating the TCR-activated
      PTK.

PMID- 1380034
TI  - Identification of subsets of human T cells capable of enhanced transendothelial
      migration.
AB  - A critical step in immunologically mediated inflammation is the migration of T
      cells between endothelial cells of postcapillary venules and into the tissues. To
      determine whether specific cells are capable of transendothelial migration, T
      cells that had migrated through endothelial monolayers were retrieved and
      analyzed. To accomplish this, human umbilical vein endothelial cells (EC) were
      cultured to confluence on collagen gels and incubated with human T cells. T cells
      that were nonadherent to the EC, those that bound to the endothelium, and cells
      that had migrated through the endothelial monolayer and into the collagen were
      individually harvested and characterized. After a 4-h incubation with EC, T cells
      distributed themselves such that 77 +/- 2% were nonadherent, 13 +/- 2% were bound
      to EC, and 10 +/- 1% had migrated into the collagen. The CD4+ T cells that had
      migrated into the collagen were predominantly CD29bright/CD45RObright and CD45RA
      . CD8+ T cells demonstrated a greater transendothelial migratory capacity than
      the CD4+ T cells. The migrated CD8+ T cells were mainly CD29bright but CD45RA+.
      Additional phenotypic analysis of the migrating cells indicated that they
      contained fewer cells that expressed L-selectin. Moreover the surface expression
      of CD7 was less dense in the T cells that had migrated than in the nonadherent T
      cells. Finally the T cells that migrated were not enriched for CD45RBdim T cells.
      Prolonging the incubation with EC to 36 h increased the number of T cells that
      migrated but did not alter the predominance of CD29bright T cells in the migrated
      population. Stimulation of EC with IL-1 or IFN-gamma also increased the number of
      adherent and migrating T cells, respectively, but did not alter the phenotype of
      the migrating cells. These results indicate that the capacity for
      transendothelial migration is an intrinsic ability of certain subpopulations of T
      cells and is related to their stage of differentiation as identified by their
      surface phenotype.

PMID- 1380035
TI  - Receptor-mediated activation of human B lymphocytes in a nonphosphotyrosine
      dependent manner.
AB  - The B cell AgR regulates two signal transduction pathways: the tyrosine kinase
      and the phosphatidylinositol (PtdIns) pathways. Stimulation of B cells with Ag or
      anti-Ig antibody results in a rapid increase in tyrosine phosphorylation of
      multiple substrates. The AgR also mediates the activation of phospholipase C
      gamma 1 (PLC-gamma 1) thus producing the second messengers, inositol
      trisphosphate and diacylglycerol. Although the detailed relationship between
      these two signaling pathways remains unclear, it has recently become apparent
      that PLC-gamma 1 might be a target for the AgR-associated protein tyrosine
      kinase. To address the question of whether tyrosine kinase activity is essential
      for B cell activation, we studied early biochemical changes and later cellular
      events induced by ligation of the purinoceptor (P2R). Ligation of ATP to its
      receptor on B cells has been previously shown to elicit increases in cytosolic
      free Ca2+ and inositol phosphate production as well as induction of c-fos mRNA
      expression and increased expression of IL-2 and transferrin receptors. We show
      here that ATP in a wide range of concentrations did not increase protein tyrosine
      kinase activity. In contrast with the AgR, P2R did not mediate tyrosine
      phosphorylation of PLC-gamma 1, thus suggesting that it may use another
      phosphoinositide-specific PLC that does not require phosphorylation on tyrosine
      residues for its activation. The results were supported by experiments with a
      specific tyrosine kinase inhibitor, tyrphostin AG-126. Preincubation with this
      inhibitor blocked AgR but not P2R-mediated inositol phosphate production,
      cytosolic free Ca2+ changes, and IL-2 and transferrin receptor expression. The
      results indicate that the PtdIns pathway may be sufficient to induce activation
      of B cells and that the tyrosine phosphorylation pathway is not necessary for
      nonantigenic B cell activation.

PMID- 1380036
TI  - Molecular cloning and characterization of the gene encoding mouse melanoma
      antigen by cDNA library transfection.
AB  - We have isolated a cDNA (H52) of 2.8-kb-long encoding an 80-kDa mouse melanoma Ag
      that is defined by a syngeneic anti-B16 melanoma mAb with an ability to block
      anti-melanoma cytotoxic T cell responses. H52 transfectants were brightly stained
      with the antibody, and the 80-kDa molecule was immunoprecipitated from the
      transfectants. Northern blot analysis showed that this transcript was detected in
      mouse melanoma cells of C57BL/6 and DBA/2 origin, C1300 A/J neuroblastoma, L cell
      (C3H) and EL-4 T lymphoma (C57BL/6), faintly in BW5147 (AKR) T lymphoma, but not
      in other tumors, such as S913 fibrosarcoma (C57BL/10), NIH3T3, 70 Z/3 pre-B
      lymphoma, and P3U1 plasmacytoma (BALB/c). Since the transcripts were not found in
      normal C57BL/6 tissues of fetus, newborn, and adult origin, the H52 expression is
      associated with transforming phenotypes. However, no tissue- or cell type
      specific expression was observed. Nucleotide sequence analysis has clearly
      demonstrated that H52 cDNA encodes the full length of the env gene and long
      terminal repeat region of endogenous ecotropic murine leukemia provirus of AKV
      type, which is defective in C57BL/6. The H52 envelope protein has several amino
      acid changes compared to those of AKV, one of which is in the env 14 peptide
      region preferentially associated with MHC molecule, suggesting the possible
      reason for the difference of antibody reactivity even in H52-positive tumors. We
      also demonstrate that CTL against H52 transfectant kills B16 melanoma. Thus, the
      above results are direct evidence that even the endogenous self molecule, when
      constitutively expressed, does act as a tumor Ag.

PMID- 1380037
TI  - Oncostatin M is a differentiation factor for myeloid leukemia cells.
AB  - Oncostatin M (OSM) is a 28-kDa glycoprotein produced by stimulated macrophages
      and T lymphocytes that inhibits the proliferation of a number of different cell
      lines derived from solid tumors. Analysis of both amino acid sequence and gene
      structure has demonstrated that OSM is a member of a cytokine family that
      includes leukemia inhibitory factor (LIF), IL-6, and granulocyte colony
      stimulating factor (G-CSF). We demonstrate that, like LIF, IL-6 and G-CSF, OSM
      can induce the differentiation of the myeloblastic M1 murine leukemia cells into
      macrophage-like cells. The morphologic and functional changes induced by OSM are
      more similar to those observed with LIF and IL-6 than those induced with G-CSF.
      OSM can also induce the differentiation of the histiocytic U937 human leukemia
      cells in the presence of granulocyte-macrophage CSF, a property shared with LIF
      and IL-6. In murine M1 cells, binding of labeled OSM is completely inhibited by
      excess LIF or OSM, reflecting the binding of OSM to the high affinity form of the
      murine LIF receptor. In contrast, the binding of labeled OSM to human U937
      leukemia cells is inhibited by OSM, but the inhibition by LIF is significantly
      less. These results suggest that, in human leukemia cells, OSM may act through
      the LIF receptor and an OSM-specific receptor. The existence of an OSM-specific
      receptor was confirmed by both growth inhibition and competition binding assays
      on A375 human melanoma cells. The growth of human A375 cells was inhibited by OSM
      and IL-6 but not LIF or G-CSF. Neither LIF, G-CSF, nor IL-6 could compete with
      the binding of labeled OSM to A375 cells.

PMID- 1380038
TI  - Components of the protein kinase C pathway induce Ia expression after injection
      into macrophages.
AB  - Macrophages are activated by a variety of microbial and cytokine stimuli. One
      feature of activation is the induction of class II Ag (Ia) on the cell surface.
      To understand the intracellular events that occur during activation, we
      investigated various agents with intracellular activities, and examined their
      effects on the induction of Ia. We first noted that several agents that activate
      protein kinase C (PKC) induced Ia, and that several inhibitors of PKC inhibited
      Ia induction by IFN-gamma. To directly test whether PKC induced Ia, we
      microinjected normal peritoneal macrophages with this enzyme and other
      intracellular mediators, then examined Ia expression. We observed that injection
      of PKC itself, or of other intracellular proteins thought to participate in the
      PKC pathway (Ras or phospholipase C gamma) strongly induced Ia expression. The Ia
      inducing activity of transforming Ras protein was blocked by kinase inhibitor
      treatment of cells, suggesting that Ras signal transduction requires kinase
      activity. On the other hand, components of the protein kinase A pathway
      (phospholipase A2 and protein kinase A itself) did not induce Ia. Thus, the PKC
      pathway can control expression of macrophage surface Ia, possibly by regulating
      the genes of the MHC, and may play many other roles in the activation of
      macrophages.

PMID- 1380039
TI  - Immunization with soluble protein-pulsed spleen cells induces class I-restricted
      cytotoxic T lymphocytes that recognize immunodominant epitopic peptides from
      Plasmodium falciparum and HIV-1.
AB  - CTL lines specific for two different proteins derived from the human pathogens,
      Plasmodium falciparum (malaria) circumsporozoite protein and HIV-1 reverse
      transcriptase, were obtained by immunizing mice with protein-pulsed syngeneic
      spleen cells. The lysis of the target cells was dependent on a class I MHC
      molecule and the accessory molecule CD8. Immunodominant epitopic peptides were
      identified previously in the two proteins using murine CTL derived after
      immunization with recombinant virus or sporozoites, or using CTL from HIV-1
      infected patients. These peptides were also recognized by the CTL lines obtained
      after protein-pulsed spleen-cell immunization. A new CTL antigenic determinant
      was localized in HIV-1 reverse transcriptase to residues 514 to 528, a sequence
      that, if folded as an alpha-helix, would be strongly amphipathic. The determinant
      was tentatively narrowed, using overlapping peptides, to a core of at least nine
      residues, 515 to 523. This site was also recognized by CTL obtained by the two
      different methods of immunization. Therefore, extracellular proteins incubated
      with spleen cells can be processed and presented in vivo in the same way as
      intracellular proteins, resulting in recognition of the same epitopes in
      association with the same class I MHC molecules. The potential implications for
      vaccine development and for the understanding of class I-restricted Ag
      presentation are discussed.

PMID- 1380040
TI  - A recombinant malaria protein that can induce Th1 and CD8+ T cell responses
      without antibody formation.
AB  - Inbred strains of mice were immunized with p190-3, a 38-kDa recombinant protein
      derived from p190, a major merozoite surface Ag of the malaria parasite
      Plasmodium falciparum. Ag-specific proliferative T cell responses were obtained
      in H-2b, H-2d, and H-2k mouse strains. Surprisingly, mice of the H-2b haplotype
      (e.g., C57BL/6) did not give a measurable antibody response to the recombinant
      protein administered in Freund's adjuvant, but CD8+/CD4- as well as CD4+/CD8- T
      cells specific for p190-3 could be obtained after in vivo priming and in vitro
      selection with Ag. Distinct epitopes of p190-3 recognized by the CD8+ and CD4+ T
      cells from C57BL/6 mice were identified. The CD8+ T cells could kill H-2b APC in
      the presence of the appropriate epitope-containing peptide. The p190-3-specific
      CD4+ cells isolated from C57BL/6 mice were of the Th1 type. In contrast, Th2
      cells, but no CD8+ T cells were present in a p190-3-specific line from BALB/c
      mice, which give good antibody responses to p190-3.

PMID- 1380041
TI  - Regulation of aminopeptidase-N (CD13) and Fc epsilon RIIb (CD23) expression by IL
      4 depends on the stage of maturation of monocytes/macrophages.
AB  - IL-4 has multiple biologic activities and it has been shown to have effects on B
      and T lymphocytes, mast cells, NK cells, and monocytes. We studied the influence
      of IL-4 on the expression of cell membrane determinants, in particular
      aminopeptidase-N (CD13) and Fc epsilon RIIb (CD23), on human peripheral blood
      monocytes. We compared the response of monocytes with the response of human
      alveolar macrophages and monocytic cell lines (U937 and THP1), as mature and more
      immature representatives of the mononuclear phagocyte system, respectively. A
      dose-dependent increase of the expression of CD13 Ag was observed when monocytes
      were cultured with IL-4. Kinetic analyses revealed that this induction was
      maximal after 2 to 3 days of culture and resembled the kinetics of IL-4-induced
      expression of Fc epsilon RIIb on monocytes. This IL-4-induced increase was absent
      when monocytes were cultured with IL-4 and an anti-IL-4 antiserum. Concomitantly,
      an IL-4-induced increase in leucine-aminopeptidase activity could be observed.
      Northern blot analysis showed that incubation of monocytes with IL-4 induced a
      marked increase in CD13 mRNA. Alveolar macrophages also exhibited an increase in
      CD13 Ag expression when exposed to IL-4. Surprisingly, IL-4 was unable to induce
      expression of Fc epsilon RIIb on alveolar macrophages. U937 and THP1 cells did
      not show an induction of CD13 Ag when cultured in the presence of IL-4. However,
      IL-4 did induce the expression of Fc epsilon RIIb on both cell lines, suggesting
      the presence of functional IL-4R. Our data demonstrate that IL-4 increases the
      expression of CD13 Ag on monocytes. This IL-4-induced increase can also be
      observed in more mature monocytic cells such as alveolar macrophages, but is
      absent in immature cells such as U937 or THP1 cells. This is functionally
      accompanied by an increase in leucine-aminopeptidase activity and may be part of
      the general activation of monocytes/macrophages by IL-4. In conclusion, the data
      suggest that IL-4 responsiveness, in particular the induction of CD13 Ag and Fc
      epsilon RIIb expression, may be dependent on the stage of maturation of
      monocytes/macrophages.

PMID- 1380042
TI  - Antineutrophil cytoplasmic autoantibodies in Wegener's granulomatosis recognize
      conformational epitope(s) on proteinase 3.
AB  - Although proteinase 3 (PR3) has been identified as a major autoantigen in
      Wegener's granulomatosis, the precise antibody specificity(ies) and requirements
      for epitope recognition have not been characterized. We analyzed 11 sera
      containing antineutrophil cytoplasmic antibodies (cANCA) for binding to
      azurophilic granule proteins extracted from neutrophils under various conditions
      and for binding to native or rPR3. Ten of 11 (91%) of the cANCA sera bound to PR3
      extracted by nonionic detergents when tested by immunoprecipitation or by IEF
      followed by capillary immunoblotting. Antibody binding to PR3 was retained when
      IEF was performed under dissociating conditions (8 M urea) indicating that PR3 is
      the major autoantigen in azurophilic granules and that association with other
      proteins is not required for antigenicity. In contrast, antigenicity was totally
      destroyed by exposure of PR3 to reducing agents or to low pH (less than 3.0) and
      was either lost or considerably diminished after boiling in SDS. cANCA sera also
      showed little or no binding to rPR3 expressed as a fusion protein in Escherichia
      coli or synthesized by wheat germ ribosomes in vitro. Inasmuch as PR3 enzymatic
      activity was partially retained after acid extraction, these findings indicate
      that cANCA bind to a limited number of conformational epitopes on PR3. In
      addition, IEF followed by capillary immunoblotting appears to be a sensitive and
      specific method to detect anti-PR3 antibodies in Wegener's granulomatosis.

PMID- 1380043
TI  - Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion
      molecule-1 expression in synovium and on fibroblast-like synoviocytes.
AB  - Expression of vascular cell adhesion molecule-1 (VCAM-1) in synovial tissue was
      determined using the immunoperoxidase technique. Normal, rheumatoid arthritis
      (RA), and osteoarthritis (OA) synovia bound VCAM-1 antibodies in the intimal
      lining as well as blood vessels. The amount of VCAM-1 was significantly greater
      in the synovial lining of RA and OA tissues compared with normal synovium (p less
      than 0.002). There was also a trend toward greater levels of VCAM-1 staining in
      blood vessels of arthritic tissue (RA greater than OA greater than normal).
      Because VCAM-1 staining was especially intense in the synovial lining, VCAM-1
      expression and regulation was studied on cultured fibroblast-like synoviocytes
      (FLS) derived from this region. Both VCAM-1 and intercellular adhesion molecule 1
      were constitutively expressed on FLS. VCAM-1 expression was further increased by
      exposure to IL-1 beta, TNF-alpha, IL-4, and IFN-gamma. These cytokines (except
      for IL-4) also induced intercellular adhesion molecule 1 expression on FLS. ELAM
      was not detected on resting or cytokine-stimulated FLS. The specificity of VCAM-1
      for FLS was demonstrated by the fact that only trace amounts were detected on
      normal and RA dermal fibroblasts. Cytokines induced intercellular adhesion
      molecule 1 display on dermal fibroblasts but had minimal effect on VCAM-1
      expression. Finally, in adherence assays, Jurkat cell binding to resting FLS
      monolayers was inhibited by antibody to alpha 4/beta 1 integrin (VLA-4), CS-1
      peptide from alternatively spliced fibronectin (which is another VLA-4 ligand),
      and, to a lesser extent, anti-VCAM-1 antibody. After cytokine stimulation of FLS,
      Jurkat-binding significantly increased, and this increase was blocked by anti
      VCAM-1 antibody. Therefore, both CS-1 and VCAM-1 participate in VLA-4-mediated
      adherence to resting FLS in vitro, and VCAM-1 is responsible for the increase in
      Jurkat binding mediated by cytokines.

PMID- 1380044
TI  - Characterization of a tolerogenic T cell epitope of type II collagen and its
      relevance to collagen-induced arthritis.
AB  - A synthetic peptide representing sequences of type II collagen, (CII 245-270),
      has previously been used to induce tolerance and suppress arthritis in DBA/1
      mice. To determine important residues, a series of peptides, each containing one
      or two site-directed substitutions, was generated. Mononuclear cells from DBA/1
      mice immunized with CII were cultured in the presence of each peptide and the T
      cell response determined by measuring IFN-gamma in culture supernatant fluids.
      Substitutions within the region CII 260-270 led to significant decreases in IFN
      gamma responses, identifying this sequence as a T cell epitope. To determine the
      effects of substitutions within this epitope on arthritis, substituted peptides
      were administered to neonatal mice as tolerogens. Five site-directed
      substitutions, four of which included the insertion of a residue found in type I
      collagen to replace its type II counterpart, abrogated the ability of the
      peptides to induce tolerance and suppress arthritis. These substitutions were
      located at residues 260, 261, 263, 264, and 266. Two patterns of T cell
      reactivity were observed. Peptides containing individual substitutions at
      positions 261, 264, or 266 were capable of generating a significant T lymphokine
      response, although those containing substitutions at residues 260 or 263 were
      ineffective Ag. Systematic analysis of the fine structures of T cell determinants
      important for autoimmune arthritis can lead to strategies for therapeutic
      intervention.

PMID- 1380045
TI  - The immunopathology of acute experimental allergic encephalomyelitis induced with
      myelin proteolipid protein. T cell receptors in inflammatory lesions.
AB  - To determine whether there is predominance of T cells expressing a particular TCR
      V beta chain in the inflammatory lesions of an autoimmune disease model, TCR
      expression was analyzed in central nervous system (CNS) tissues of mice with
      experimental allergic encephalomyelitis (EAE). Acute EAE was induced in SJL/J
      mice either by sensitization with a synthetic peptide corresponding to myelin
      proteolipid protein residues 139-151 or by adoptive transfer of myelin
      proteolipid protein peptide 139-151-specific encephalitogenic T cell clones. Mice
      were killed when they showed clinical signs of EAE or by 40 days after
      sensitization or T cell transfer. Cryostat CNS and lymphoid tissue sections were
      immunostained with a panel of mAb to T cell markers and proportions of stained
      cells were counted in inflammatory foci. In mice with both actively induced and
      adoptively transferred EAE, infiltrates consisted of many CD3+, TCR alpha beta+,
      and CD4+ cells, fewer CD8+ cells, and small numbers of TCR gamma delta+ cells.
      Approximately 30% of CD45+ leukocytes in the inflammatory foci were T cells.
      Cells expressing TCR V beta 2, 3, 4, 6, 7 and 14 were detected in the
      infiltrates, whereas TCR V beta 8 and 11, which that are deleted in SJL mice,
      were absent. When EAE was induced by transfer of T cell clones that use either V
      beta 2, 6, 10, or 17, there was also a heterogeneous accumulation of T cells in
      the lesions. Similar proportions of TCR V beta+ and gamma delta+ cells were
      detected in EAE lesions and in the spleens of the mice. Thus, at the time that
      clinical signs are present in acute EAE, peripherally derived, heterogeneous TCR
      V beta+ cells are found in CNS lesions, even when the immune response is
      initiated to a short peptide Ag or by a T cell clone using a single TCR V beta.

PMID- 1380046
TI  - Isolation of sequences from a random-sequence expression library that mimic viral
      epitopes.
AB  - We describe the use of random peptide sequences for the mapping of antigenic
      determinants. An oligonucleotide with a completely degenerate sequence of 17 or
      23 nucleotides was inserted into a bacterial expression vector. This resulted in
      an expression library producing random hexa- or octapeptides attached to a beta
      galactosidase hybrid protein. Mimotopes, or antigenic sequences that mimic an
      epitope, were selected by immunoscreening of colonies with monoclonal antibodies,
      which were specific for antigenic sites on the spike protein of the coronavirus
      transmissible gastroenteritis virus. We report one mimotope for antigenic site
      II, eight for site III and one for site IV. The site III and site IV mimotopes
      were closely similar to the corresponding linear epitopes, localized previously
      in the amino acid sequence of the S protein. An alignment of the site II mimotope
      and the sequence of the S protein around Trp97, which is substituted in escape
      mutants, suggests that this mimotope mimics a conformational epitope located
      around residues 97-103. Applications of mimotopes to epitope mapping,
      serodiagnosis and vaccine development are discussed.

PMID- 1380047
TI  - Kinetics of killing by monoclonal cytotoxic T lymphocytes. I. Colorimetric
      detection of cryptic CTL determinants on adherent target cells and survivorship
      analysis.
AB  - Some targets of cell-mediated cytolysis do not efficiently release 51Cr but
      manifestly are killed in direct viability assays. We characterize and validate an
      alternative and non-radioactive (colorimetric) method for measuring killing of
      adherent targets by monoclonal CTL. The method obviates concerns about the
      effects of trypsinization, is technically simple, quantitative and in some cases
      more sensitive than conventional 51Cr assays. Target loss obeyed first-order
      kinetics with respect both to [CTL] and time. These results are consistent with
      an exponential (Poisson) model of killing and support the use of a single kinetic
      parameter to describe the lytic activity of monoclonal CTL on adherent targets.
      When monoclonal CTL are used at appropriate effector:target ratios (less than or
      equal to 1:1), the residuals obtained after least squares linear regression are
      homoscedastic and normally distributed, justifying the use of commonly available
      statistical calculators or programs for the analysis of CTL data.

PMID- 1380048
TI  - Analysis of B lymphocyte cross-reactivity at the single cell level.
AB  - A method is described for assaying whether individual in vivo activated B cells
      produce antibodies which cross-react with two distinct antigens. The technique
      utilizes a modification of the ELISA spot assay to determine the isotype and
      antigenic specificity(s) of these antibody secreting cells. To perform the assay,
      two plastic slides are coated with different antigens and secured together to
      form chambers capable of holding a monolayer of Ig secreting lymphocytes. The
      immunoglobulin secreted during culture binds to one or both sides of the antigen
      coated chamber (depending upon the specificity and cross-reactivity of the
      antibody product). This technique was used to evaluate the cross-reactivity of
      hybridomas and freshly isolated IgM and IgG secreting B cells.

PMID- 1380049
TI  - Detection of rotaviruses in the day care environment by reverse transcriptase
      polymerase chain reaction.
AB  - Group A rotavirus is an important cause of morbidity among infants and toddlers
      in day care centers. Transmission by the fecal-oral route is well established,
      but fomites and environmental surfaces may also play an important role in
      transmission. A highly sensitive polymerase chain reaction (PCR) assay was used
      to detect rotavirus RNA in day care environments. Areas sampled included floors,
      diaper change areas, toy balls, and other surfaces. In two centers undergoing
      outbreaks of rotavirus, 7 (39%) of 18 toy balls had detectable rotavirus as did 8
      (21%) of 39 swabs from environmental surfaces. By comparison, only 1 (5%) of 21
      toy balls and 1 (2%) of 44 environmental surface swabs had detectable rotavirus
      in centers without rotavirus outbreaks (P = .0001). Thus, rotaviruses are highly
      prevalent in day care centers during outbreaks of diarrhea. The monitoring of
      environments by sensitive nucleic acid amplification techniques may lead to
      strategies for the diminution of disease transmission within the day care
      environment.

PMID- 1380050
TI  - Molecular epidemiology of group B streptococcal infections: use of restriction
      endonuclease analysis of chromosomal DNA and DNA restriction fragment length
      polymorphisms of ribosomal RNA genes (ribotyping).
AB  - Epidemiologic investigation of group B streptococcal (GBS) infections has been
      limited by the lack of a discriminatory typing system. Therefore, the use of
      restriction endonuclease analysis of chromosomal DNA (REAC) and DNA restriction
      fragment length polymorphisms of rRNA genes (ribotyping) to subtype molecularly
      GBS isolates associated with human invasive disease was investigated. Chromosomal
      DNA of selected GBS isolates was initially digested with 24 different restriction
      enzymes. HhaI gave the best discrimination of hybridization banding patterns
      (ribotypes) and was used with all study isolates. Ribotyping and REAC
      differentiated among isolates of the same and different serotypes. Nine ribotype
      patterns were noted among the 76 isolates studied, including 4 among serotype
      Ia/c and 4 additional ribotypes among serotype III isolates. Epidemiologically
      related isolates (e.g., mother-infant or twin-twin pairs) had identical REAC and
      ribotype patterns. Epidemiologically unrelated isolates with the same ribotype
      usually had different REAC patterns, suggesting that REAC may be a more sensitive
      technique for strain differentiation. REAC and ribotyping were reproducible and
      proved to be successful molecular epidemiologic methods for subtyping GBS.

PMID- 1380051
TI  - Epitopes of herpes simplex virus type 1 glycoprotein B that bind type-common
      neutralizing antibodies elicit type-specific antibody-dependent cellular
      cytotoxicity.
AB  - A panel of 45 well-characterized monoclonal antibodies (MAbs) reactive to
      glycoprotein B (gB) of herpes simplex virus (HSV) type 1 was tested by ELISA and
      in antiviral functional assays (that included virus neutralization, antibody
      dependent cellular cytotoxicity (ADCC), and antibody-dependent complement
      mediated lysis), using type 1 or 2 virus strains. All MAbs were ELISA-reactive.
      Eleven of the MAbs mediated neutralization and 9 mediated ADCC. All of the ADCC
      epitopes were contained within the amino-terminal half of the extracellular
      portion of gB. The ADCC reactions were strictly type 1-specific, whereas 9 of 11
      neutralizing MAbs exhibited type-common activity. There was some association
      between the ADCC and neutralization activities, since of 12 MAbs with functional
      activity, 8 were positive in both assays. These results suggest that differences
      in the presentation of gB, and perhaps HSV-1 gB versus HSV-2 gB, on free virus
      and virus-infected cells determine epitope availability.

PMID- 1380052
TI  - Neutrophil oxidative burst in response to blastoconidia and pseudohyphae of
      Candida albicans: augmentation by granulocyte colony-stimulating factor and
      interferon-gamma.
AB  - The effects of granulocyte colony-stimulating factor (G-CSF) and interferon-gamma
      (IFN-gamma) on the oxidative burst of neutrophils (PMNL) in response to
      blastoconidia and pseudohyphae of Candida albicans were assessed and compared
      with those in response to N-FMLP. G-CSF enhanced oxidative burst, as measured by
      superoxide production, in response to both FMLP and opsonized blastoconidia. The
      enhancement of oxidative burst in response to FMLP was significantly greater (P =
      .004) than that in response to blastoconidia (65% and 39%, respectively). G-CSF
      also enhanced oxidative burst in response to pseudohyphae. IFN-gamma enhanced
      oxidative burst in response to FMLP and opsonized blastoconidia by 53% and 50%,
      respectively. Moreover, IFN-gamma significantly enhanced oxidative burst in
      response to opsonized and nonopsonized hyphae by 86% and 65%, respectively. These
      results demonstrate that G-CSF and IFN-gamma enhance the oxidative burst of PMNL
      in response to both blastoconidia and pseudohyphae of C. albicans and suggest an
      immunomodulatory role of the two cytokines in the host defenses against this
      fungus.

PMID- 1380053
TI  - [Sequential changes of HPV DNA, the expression of EGF-R and CD-14, and
      histopathological findings in HPV infected benign epithelium and dysplastic
      lesions of the uterine cervix].
AB  - In regard to cases in which HPV DNA was detected in the uterine cervix by the
      Southern blot method, we studied both changes in HPV DNA and histological
      diagnosis, and moreover we studied the relationship between CD-14
      (monocyte/macrophage), EGF-R, and HPV DNA. 1) Changes in HPV DNA, regardless of
      the HPV type in benign lesions of the uterine cervix, almost all became negative
      within 1 year. 2) In 1 year benign lesions, the manifestation frequency of CD-14
      was higher from the initial examination and during the subsequent 3 months when
      HPV DNA was detected. 3) HPV DNA in cases of mild dysplasia was detected after 1
      year in 41% (7/17), but it continued for 3 years only in 3 cases. 4) Cases of
      moderate to severe dysplasia, which are though to have developed cancer at an
      early period of within 1-1.5 years included 26.7% (4/15), and HPV DNA was
      continually detected in them. The characteristics of these cases were: (1) The
      HPV 16 type was the main type. (2) The mean age was 34.8 years, which was younger
      than in regressed cases with a mean age of 43.1 years. (3) The dysplasia
      occupation rate in the uterine cervix was higher. 5) In 7 cases of moderate to
      severe dysplasia which regressed from squamous metaplasia, HPV DNA was detected
      at 1 year in 71.4% (5/7), but at 2-3 years it became undetectable in all cases,
      so that it has a close relationship with this histological regression.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380054
TI  - [A case of ovarian endodermal sinus tumor relapsed into remained ovary at 4 years
      and 9 months after the first operation].

PMID- 1380055
TI  - Epidermal growth factor stimulates production of insulin-like growth factor
      binding protein-1 in human granulosa-luteal cells.
AB  - Insulin-like growth factor-I (IGF-I) enhances and epidermal growth factor (EGF)
      inhibits gonadotrophin-induced aromatization in granulosa cells. Our previous
      studies have shown that human ovarian granulosa cells synthesize insulin-like
      growth factor-binding protein-1 (IGFBP-1) which inhibits IGF-stimulated DNA
      synthesis. The present study addresses the effect of EGF and gonadotrophins in
      the regulation of IGFBP-1 release by human granulosa cells cultured in serum-free
      medium. At concentrations of 1-100 micrograms/l EGF was found to stimulate IGFBP
      1 secretion. This was not due to cell proliferation, as the viable cell count
      remained unaffected. Growth hormone and gonadotrophins had no effect on IGFBP-1
      secretion when added alone to culture medium. These results suggest that EGF
      regulates IGFBP-1 secretion in human granulosa-luteal cells.

PMID- 1380056
TI  - Radioimmunoassay of insulin-like growth factor-binding protein-6 in human serum
      and other body fluids.
AB  - A radioimmunoassay has been established for the insulin-like growth factor
      binding protein, IGFBP-6, isolated from a human transformed fibroblast cell-line.
      The binding proteins IGFBP-I and IGFBP-3 did not cross-react, but both IGF-I and
      IGF-II markedly inhibited IGFBP-6 tracer binding to antiserum. This inhibition,
      greater for IGF-II than for IGF-I, was fully reversed by the addition of IGFBP-3
      to sequester the IGFs. After fractionation of human serum and follicular fluid
      samples by gel chromatography, interference in the radioimmunoassay by fractions
      corresponding to the 150 kDa IGF-IGFBP complex could be eliminated by IGFBP-3.
      The equivalent fractions from cerebrospinal fluid and amniotic fluid
      fractionation did not interfere in the assay. The mean IGFBP-6 level in adult
      human serum was 0.221 +/- 0.110 mg/l, with values significantly higher in men
      than women, and slightly decreased in pregnancy. Similar values were seen in
      umbilical cord serum and in amniotic and follicular fluid samples, while the mean
      level in cerebrospinal fluid was slightly lower, 0.152 +/- 0.049 mg/l. This assay
      will facilitate studies on the regulation of IGFBP-6 production, and its role as
      an IGF carrier.

PMID- 1380057
TI  - Effects of a novel hypothalamic peptide, pituitary adenylate cyclase-activating
      polypeptide, on pituitary hormone release in rats.
AB  - We have demonstrated that the novel hypothalamic peptide pituitary adenylate
      cyclase-activating polypeptide (PACAP-38; 0.1-100 nmol/l) caused an increase in
      the release of GH, ACTH, LH and alpha-subunit and accumulation of intracellular
      cyclic AMP from dispersed rat anterior pituitary cells in static culture for 24
      h. There were no significant effects on TSH or prolactin release over the same
      time-period. PACAP-38 (10 nmol/l) increased the release of GH by 1.3-fold (P less
      than 0.05), ACTH by 1.9-fold (P less than 0.05), LH by 3.5-fold (P less than
      0.001) and alpha-subunit by 2.0-fold (P less than 0.005) and the accumulation of
      intracellular cyclic AMP by greater than 2-fold (P less than 0.001) after 24 h.
      However, the time-course for the effect of PACAP-38 (1 mmol/l) on hormone release
      and intracellular cyclic AMP levels showed a temporal dissociation. The effect of
      PACAP-38 on GH and ACTH levels did not reach significance until 24 h whereas the
      effect of PACAP-38 on LH and alpha-subunit release reached significance after 4 h
      implying a different mechanism of action for their release. To investigate the
      PACAP-induced secretion of LH and alpha-subunit further, we examined the effects
      of PACAP after down-regulation of protein kinase C (PKC). PACAP-38 at a dose
      maximal for the stimulation of LH and alpha-subunit release (10 nmol/l) added
      together with the PKC activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 0.1
      mumol/l) had no greater effect on LH and alpha-subunit release than TPA alone
      over a 4 h incubation period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380058
TI  - Growth hormone treatment increases oestrogen receptor concentration in the guinea
      pig uterus.
AB  - Growth hormone does not act as a body growth-promoting hormone during the
      postnatal period in the guinea-pig. To determine whether it affects uterine and
      mammary growth, guinea-pigs of 8-9 weeks of age were treated with either
      recombinant bovine GH (bGH; 0.5 mg per animal) or vehicle for 10 days. Uterine
      and mammary weights were not changed by treating the animals with bGH. The amount
      of available cytosolic oestradiol receptor per unit of uterine weight or DNA
      content, or in whole uteri was increased in bGH-treated animals (7.3- to 14.0
      fold) when compared with controls. The nuclear uterine oestradiol receptor
      concentration was 3.3- to 6.7-fold higher than in controls. The dissociation
      constant values did not differ between control and bGH-treated animals,
      suggesting that uterine oestradiol receptors are regulated by GH through changes
      in the number of binding sites rather than alteration of their binding affinity.
      Mammary growth and oestradiol receptor levels were unaffected by bGH treatment.
      The results of this investigation demonstrate that injected bGH selectively
      affects the oestradiol receptor level in guinea-pig uterine tissue.

PMID- 1380059
TI  - Characterization of the lymphocyte activation gene 3-encoded protein. A new
      ligand for human leukocyte antigen class II antigens.
AB  - The lymphocyte activation gene 3 (LAG-3), expressed in human activated T and
      natural killer (NK) cells, is closely related to CD4 at the gene and protein
      levels. We report here the initial characterization of the LAG-3-encoded protein.
      We have generated two monoclonal antibodies after immunization of mice with a 30
      amino acid peptide that corresponds to an exposed extra loop region present in
      the LAG-3 immunoglobulin-like first domain. The reactivity of these reagents is
      directed against LAG-3 since they recognize both membrane-expressed and soluble
      recombinant LAG-3 molecules produced in a baculovirus expression system. The two
      antibodies are likely to react with the same or closely related epitope (termed
      LAG-3.1) exposed on the LAG-3 first domain extra loop, as assessed in competition
      experiments on LAG-3-expressing activated lymphocytes. Cellular distribution
      analysis indicated that the LAG-3.1 epitope is expressed on activated T (both
      CD4+ and CD8+ subsets) and NK cells, and not on activated B cells or monocytes.
      In immunoprecipitation experiments performed on activated T and NK cell lysates,
      a 70-kD protein was detected after SDS-PAGE analysis. 45-kD protein species were
      also immunoprecipitated. Both the 70- and 45-kD proteins were shown to be N
      glycosylated. In Western blot analysis, only the former molecule was recognized
      by the anti-LAG-3 antibodies, demonstrating that it is LAG-3 encoded. These anti
      LAG-3 antibodies were used to investigate whether the LAG-3 protein interacts
      with the CD4 ligands. By using a high-level expression cellular system based on
      COS-7 cell transfection with recombinant CDM8 vectors and a quantitative cellular
      adhesion assay, we demonstrate that rosette formation between LAG-3-transfected
      COS-7 cells and human leukocyte antigen (HLA) class II-bearing B lymphocytes is
      specifically dependent on LAG-3/HLA class II interaction. In contrast to CD4, LAG
      3 does not bind the human immunodeficiency virus gp120. This initial
      characterization will guide further studies on the functions of this molecule,
      which may play an important role in immune responses mediated by T and NK
      lymphocytes.

PMID- 1380060
TI  - In vitro proliferation of primitive hemopoietic stem cells supported by stromal
      cells: evidence for the presence of a mechanism(s) other than that involving c
      kit receptor and its ligand.
AB  - The preadipose cell line, PA6, can support long-term hemopoiesis. Frequency of
      the hemopoietic stem cells capable of sustaining hemopoiesis in cocultures of
      bone marrow cells and PA6 cells for 6 wk was 1/5.3 x 10(4) bone marrow cells. In
      the group of dishes into which bone marrow cells had been inoculated at 2.5 x
      10(4) cells/dish, 3 of 19 dishes (16%) contained stem cells capable of
      reconstituting erythropoiesis of WBB6F1-W/Wv mice, indicating that PA6 cells can
      support the proliferation of primitive hemopoietic stem cells. When the
      cocultures were treated with an antagonistic anti-c-kit monoclonal antibody,
      ACK2, only a small number of day 12 spleen colony-forming units survived; and
      hemopoiesis was severely reduced. However, when the cocultures were continued
      with antibody-free medium, hemopoiesis dramatically recovered. To examine the
      proliferative properties of the ACK2-resistant stem cells, we developed a colony
      assay system by modifying our coculture system. Sequential observations of the
      development of individual colonies and their disappearance demonstrated that the
      stem cells having higher proliferative capacity preferentially survive the ACK2
      treatment. Furthermore, cells of subclones of the PA6 clone that were incapable
      of supporting long-term hemopoiesis expressed mRNA for the c-kit ligand. These
      results suggest that a mechanism(s) other than that involving c-kit receptor and
      its ligand plays an important role in the survival and proliferation of primitive
      hemopoietic stem cells.

PMID- 1380061
TI  - H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors
      of limited diversity.
AB  - We previously showed that H-2Kd-restricted cytotoxic T lymphocyte (CTL) clones
      specific for a single nonapeptide derived from the Plasmodium berghei
      circumsporozoite (PbCS) protein displayed T cell receptors (TCRs) of highly
      diverse primary structure. We have now analyzed the TCR repertoire of CTLs that
      recognize a peptide derived from the human class I major histocompatibility
      complex (MHC) molecule HLA-Cw3 in association with the same murine class I MHC
      molecule H-2Kd. We first sequenced the TCR alpha and beta genes of the CTL clone
      Cw3/1.1 and, based on this genomic analysis, the TCR alpha and beta cDNA
      junctional regions of 23 independent H-2Kd-restricted CTL clones specific for HLA
      Cw3. The results show that the TCR chains display very limited heterogeneity,
      both in terms of V alpha, J alpha, V beta, and J beta segments, and in terms of
      length and sequence of the CDR3 alpha and beta loops. The TCR repertoire used in
      vivo was then analyzed by harvesting CTL populations from the peritoneal cavity
      of immune mice. The peritoneal exudate lymphocytes (PELs) displayed HLA-Cw3
      specific cytolytic activity in the absence of any stimulation in vitro.
      Remarkably, most of these freshly isolated PELs expressed TCRs that shared the
      same structural features as those from HLA-Cw3-reactive CTL clones. Thus, our
      results show that a peptide from HLA-Cw3 presented by H-2Kd selects CTLs that
      bear TCRs of very limited diversity in vivo. When taken together with the high
      diversity of the TCRs specific for the PbCS peptide, these findings suggest that
      natural tolerance to self peptides presented by class I MHC molecules may
      substantially reduce the size of the TCR repertoire of CTLs specific for
      antigenic peptides homologous to self.

PMID- 1380062
TI  - Cytotoxic T lymphocytes (CTL) against a transforming gene product select for
      transformed cells with point mutations within sequences encoding CTL recognition
      epitopes.
AB  - The 94-kD large tumor (T) antigen specified by simian virus 40 (SV40) is
      sufficient to induce cell transformation. T antigen contains four H-2Db
      restricted cytotoxic T lymphocyte (CTL) recognition epitopes that are targets for
      CTL clones Y-1, Y-2, Y-3, and Y-5. These epitopes have been mapped to T antigen
      amino acids 207-215 (site I), 223-231 (sites II and III), and 489-497 (site V),
      respectively. Antigenic site loss variant cells that had lost one or more CTL
      recognition epitopes were previously selected by coculturing SV40-transformed H
      2Db cells with the site-specific Db-restricted CTL clones. The genetic bases for
      T antigen CTL recognition epitope loss from the variant cells were identified by
      DNA amplification and direct sequencing of epitope-coding regions from variant
      cell DNAs. Cells selected for resistance to CTL clone Y-1 (K-1; K-1,4,5; K-3,1)
      carry deleted SV40 genomes lacking site I, II, and III coding sequences. Point
      mutations present within the site II/III coding region of Y-2-/Y-3-resistant cell
      lines specify the substitution of asparagine for lysine as T antigen amino acid
      228 (K-2) or phenylalanine for tyrosine at position 230 (K-3). Point mutations
      identified within independently selected Y-5 resistant populations (K-5 and K
      1,4,5) direct the substitution of isoleucine for asparagine at position 496 (K-5)
      or the substitution of phenylalanine for isoleucine at position 491 (K-1,4,5) of
      T antigen. Each substitution causes loss of the relevant CTL recognition epitope,
      apparently by compromising CTL T cell receptor recognition. These experiments
      identify specific amino acid changes within a transforming protein that
      facilitate transformed cell escape from site-specific CTL clones while allowing
      maintenance of cellular transformation. This experimental model system provides
      unique opportunities for studying mechanisms of transformed cell escape from
      active immunosurveillance in vivo, and for analysis of differential host immune
      responses to wild-type and mutant cell-transforming proteins.

PMID- 1380063
TI  - Lipopolysaccharide (LPS) partial structures inhibit responses to LPS in a human
      macrophage cell line without inhibiting LPS uptake by a CD14-mediated pathway.
AB  - Lipopolysaccharides (LPS) that lack acyloxyacyl groups can antagonize responses
      to LPS in human cells. Although the site and mechanism of inhibition are not
      known, it has been proposed that these inhibitory molecules compete with LPS for
      a common cellular target such as a cell-surface binding receptor. In the present
      study, we used an in vitro model system to test this hypothesis and to evaluate
      the role of CD14 in cellular responses to LPS. Cells of the THP-1 human monocyte
      macrophage cell line were exposed to 1,25 dihydroxyvitamin D3 to induce adherence
      to plastic and expression of CD14, a binding receptor for LPS complexed with LPS
      binding protein (LBP). The uptake of picograms of [3H]LPS (agonist) and
      enzymatically deacylated LPS [3H]dLPS (antagonist) was measured by exposing the
      cells to the radiolabeled ligands for short incubation periods. The amounts of
      cell-associated LPS and dLPS were then correlated with cellular responses by
      measuring the induction of nuclear NF-kappa B binding activity and the production
      of cell-associated interleukin (IL)-1 beta. We found that similar amounts of
      [3H]LPS or [3H]dLPS were taken up by the cells. The rate of cellular accumulation
      of the ligands was greatly enhanced by LBP and blocked by a monoclonal antibody
      to CD14 (mAb 60b), yet no cellular responses were induced by dLPS or dLPS-LBP
      complexes. In contrast, LPS stimulated marked increases of NF-kappa B binding
      activity and IL-1 beta. These responses were enhanced by LBP and inhibited by mAb
      60b. dLPS and its synthetic lipid A counterpart, LA-14-PP (also known as lipid
      Ia, lipid IVa, or compound 406) strongly inhibited LPS-induced NF-kappa B and IL
      1 beta, yet neither antagonist inhibited the uptake of LPS via CD14. dLPS did not
      inhibit NF-kappa B responses to tumor necrosis factor (TNF) alpha or phorbol
      ester. Our results indicate that (a) both stimulatory and nonstimulatory ligands
      can bind to CD14 in the presence of LBP; (b) the mechanism of inhibition by dLPS
      is LPS-specific, yet does not involve blockade of LPS binding to CD14; and (c) in
      keeping with previous results of others, large concentrations of LPS can
      stimulate the cells in the absence of detectable binding to CD14. The findings
      indicate that the site of dLPS inhibition is distal to CD14 binding in the LPS
      signal pathway in THP-1 cells, and suggest that molecules other than CD14 are
      important in LPS signaling.

PMID- 1380064
TI  - Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant
      for human eosinophils.
AB  - Thrombin stimulation of human platelets results in the release of a preformed
      proteinaceous human eosinophil (Eo)-chemotactic activity. By the use of different
      high-performance liquid chromatography techniques, two Eo-chemotactic
      polypeptides (EoCPs), tentatively termed EoCP-1 and EoCP-2, were purified to
      homogeneity. Upon SDS-PAGE analysis, these chemotaxins showed molecular masses
      near 8 kD. NH2-terminal amino acid sequence analysis revealed identical sequences
      for both EoCP-1 and EoCP-2, which are also identical to that of RANTES, a
      cytokine that structurally belongs to the interleukin 8 superfamily of leukocyte
      selective attractants, and that is known to be a "memory-type" T lymphocyte
      selective attractant. In the major Eo chemotaxin, EoCP-1, the residues 4 and 5,
      which in EoCP-2 were found to be serine residues, could not be identified.
      Electrospray mass spectrometry (ESP-MS) of EoCPs revealed for EoCP-2 a molecular
      mass of 7,862.8 +/- 1.1 daltons, which is 15.8 mass units higher than the
      calculated value of RANTES, indicating that EoCP-2 is identical to the full
      length cytokine, and oxygenation, probably at methionine residue number 64, has
      taken place. Upon ESP-MS, EoCP-1 showed an average molecular mass of 8,355 +/- 10
      daltons, suggesting O-glycosylation at these serine residues. Both natural forms
      of RANTES showed strong Eo-chemotactic activity (ED50 = 2 nM) with optimal
      chemotactic migration at concentrations near 10 nM, however, there were no
      significant migratory responses with human neutrophils. Chemotactic activity of
      RANTES for human Eos could be confirmed using recombinant material, which has
      been found to be as active as the natural forms. Since RANTES gene expression has
      been detected in activated T lymphocytes, and recombinant RANTES was shown to be
      a "memory" T lymphocyte-selective attractant, it is now tempting to speculate
      about an important role of RANTES in clinical situations such as allergene
      induced late-phase skin reactions in atopic subjects or asthma, where in affected
      tissues both memory T cells and Eos are characteristic.

PMID- 1380065
TI  - Calmodulin is a subunit of nitric oxide synthase from macrophages.
AB  - A central issue in nitric oxide (NO) research is to understand how NO can act in
      some settings as a servoregulator and in others as a cytotoxin. To answer this,
      we have sought a molecular basis for the differential regulation of the two known
      types of NO synthase (NOS). Constitutive NOS's in endothelium and neurons are
      activated by agonist-induced elevation of Ca2+ and resultant binding of
      calmodulin (CaM). In contrast, NOS in macrophages does not require added Ca2+ or
      CaM, but is regulated instead by transcription. We show here that macrophage NOS
      contains, as a tightly bound subunit, a molecule with the immunologic reactivity,
      high performance liquid chromatography retention time, tryptic map, partial amino
      acid sequence, and exact molecular mass of CaM. In contrast to most CaM-dependent
      enzymes, macrophage NOS binds CaM tightly without a requirement for elevated
      Ca2+. This may explain why NOS that is independent of Ca2+ and elevated CaM
      appears to be activated simply by being synthesized.

PMID- 1380066
TI  - A polyalanine peptide with only five native myelin basic protein residues induces
      autoimmune encephalomyelitis.
AB  - The minimum structural requirements for peptide interactions with major
      histocompatibility complex (MHC) class II molecules and with T cell receptors
      (TCRs) were examined. In this report we show that substituting alanines at all
      but five amino acids in the myelin basic protein (MBP) peptide Ac1-11 does not
      alter its ability to bind A alpha uA beta u (MHC class II molecules), to
      stimulate specific T cells and, surprisingly, to induce experimental autoimmune
      encephalomyelitis (EAE) in (PL/J x SJL/J)F1 mice. Most other amino acid side
      chains in the Ac1-11 peptide are essentially irrelevant for T cell stimulation
      and for disease induction. Further analysis revealed that binding to A alpha uA
      beta u occurred with a peptide that consists mainly of alanines and only three of
      the original residues of Ac1-11. Moreover, when used as a coimmunogen with MBP
      Ac1-11, this peptide inhibited EAE. The finding that a specific in vivo response
      can be generated by a peptide containing only five native residues provides
      evidence that disease-inducing TCRs recognize only a very short sequence of the
      MHC-bound peptide.

PMID- 1380067
TI  - Identification of insulin-like growth factor-binding proteins in the circulation
      of four teleost fish species.
AB  - Insulin-like growth factor-binding proteins (IGF-BPs) were demonstrated in the
      circulation of four teleost fish species. In the coho salmon (Oncorhynchus
      kisutch), serum binding of 125I-labelled human IGF-I (125I-hIGF-I) was
      competitively inhibited by addition of excess recombinant bovine IGF-I (rbIGF-I)
      in a manner similar to that when rat serum was used. Western-ligand blot
      procedure using the same labelled hormone identified at least three major forms
      of IGF-BPs in the plasma of all four teleost species investigated: coho salmon,
      striped bass (Morone saxatilis), tilapia (Oreochromis mossambicus), and longjawed
      mudsucker (Gillichthys mirabilis). The first form is around 40-50 kDa, may be
      regulated by growth hormone (GH), and seems to be a good candidate for the fish
      version of mammalian IGF-BP3 (which is in the same size range and is GH
      regulated). The second and third forms are 29 kDa and 31 kDa and are good
      candidates for the fish versions of mammalian IGF-BP1 and IGF-BP2, respectively,
      as they appear to be regulated by insulin and are in the same size range as their
      mammalian counterparts. Functionally different classes of circulating IGF-BPs may
      be conserved between fish and mammal.

PMID- 1380068
TI  - Isoelectric focusing of human hair keratins: correlation with sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns and effect of
      cosmetic treatments.
AB  - A new isoelectric focusing (IEF) technique in polyacrylamide gels with 6M urea
      and 1.5% Nonidet P40 has been developed to characterize human hair samples. The
      phenotypes demonstrated with this procedure has been correlated with the sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns described
      by other authors. The method described can be applied in the forensic science
      analysis of a single human hair. Using the same IEF technique we have studied the
      changes in electrophoretic patterns of cosmetically treated hair. The
      characteristics of the modifications observed and its utility in forensic science
      work are also discussed in this paper.

PMID- 1380069
TI  - Brave new world of medical knowledge. Two 16th century writers and their books.

PMID- 1380070
TI  - Actions of ethanol on gamma-aminobutyric acid-activated chloride channels.
AB  - Ethanol appears to exert its intoxicating effects, at least partly, by
      potentiating gamma-aminobutyric acid (GABA) mediated inhibitory synaptic
      transmission in the brain. Work over the past decade using mouse lines selected
      for different ethanol sensitivities has implicated GABA-activated chloride
      channels as a potential target of ethanol. More recently, molecular biological
      techniques have identified a subunit (gamma 2L) of the GABA channel which appears
      to be required for the effects of ethanol on GABA channels. The presence of this
      subunit, however, cannot account for the full degree of potentiation of GABA
      responses observed in native GABA channels. Ongoing research is directed at
      identifying other factors which might be involved in the effects of ethanol on
      GABA channels and in understanding ethanol's molecular mechanism of action. Such
      information could be vital for designing drugs to combat ethanol intoxication.

PMID- 1380071
TI  - Calbindin immunoreactivity in a subset of cat thalamic reticular neurons.
AB  - Recent studies have shown that the thalamic reticular nucleus of cats is made up
      of several cytoarchitectonically distinct subdivisions and that the nucleus
      contains accurate topographical maps of the cortical sheet and of the dorsal
      thalamus. The present study describes immunocytochemically demonstrable
      heterogeneity in the reticular nucleus of cats, with an antibody to calbindin
      D28k. The striking feature of calbindin immunoreactivity in the reticular nucleus
      of cats is that the immunoreactive neurones are located in the caudal half of the
      nucleus only. In these regions, labelled cells form a small proportion of the
      total population of reticular cells only and are not distinct in somal size or
      shape from neighbouring non-labelled reticular cells. Double labelling shows that
      the calbindin-immunoreactive cells are also immunoreactive to parvalbumin and
      GABA. There is a distinct tendency for the calbindin-immunoreactive cells to be
      more numerous ventrally than dorsally in the caudal half of the nucleus, which
      receives afferents from the somatosensory and auditory systems.

PMID- 1380072
TI  - Immunohistochemical study of the distribution of S-100 protein in pleomorphic
      adenomas of minor salivary glands.
AB  - Twelve pleomorphic adenomas of minor salivary gland origin were examined for the
      distribution of S-100 protein, detected using the peroxidase-antiperoxidase (PAP)
      method. Strong S-100 protein immunoreactivity was noted in areas containing
      plasmacytoid cells, stellate and spindle cells against a myxochondroid or
      hyalinous stroma, and solid epithelial areas. Tubular and duct-like structures
      showed variable stainability. Stromal tissue and normal salivary glands were
      generally negative for S-100 protein. These findings were compared with those
      reported elsewhere.

PMID- 1380073
TI  - Initial characterization of the metabolism of intervertebral disc cells
      encapsulated in microspheres.
AB  - Adult, canine intervertebral disc cells were isolated with a sequential digestion
      of pronase and bacterial collagenase. The nonchondrodystrophoid nucleus pulposus
      exhibits two populations of cells: large notochordal cells and smaller
      chondrocyte-like cells. The cells from the transition zone and anulus fibrosus
      are uniform in size, ranging from 17 to 21 microns. The isolated cells were
      encapsulated in alginate beads and cultured in Ham's F-12 medium containing 5%
      heat-inactivated fetal bovine serum. Alginate bead formation requires calcium
      ions and can be reversed with a suitable chelator, thus releasing viable cells.
      We observed that 58% of the newly synthesized proteoglycans formed large
      molecular-weight aggregates with hyaluronic acid. The proteoglycans contained low
      amounts of keratan sulfate (KS) (less than 5% of the total glycosaminoglycans
      synthesized). The chondroitin sulfates (CS) consisted of 51-67% as 6-O-sulfate
      and 29-39% as 4-O-sulfate, with the remainder (4-10%) present as 4,6-sulfate for
      all three zones of the disc. The majority of cells synthesized significant
      amounts of matrix as evidenced by Alcian Blue staining. By immunohistochemical
      analysis, the matrix contained chondroitin 6-sulfate as demonstrated by
      monoclonal antibodies to the unsaturated disaccharides remaining on the
      proteoglycan core after chondroitinase ABC digestion. Keratan sulfate was also
      present in the majority of the matrices around cells. These results emphasize the
      similarity of the newly synthesized proteoglycans secreted by cells grown in
      alginate beads to those synthesized by the neonate disc. These experiments also
      demonstrate the usefulness of this method as a microculture technique for disc
      cells.

PMID- 1380074
TI  - Recombinant human granulocyte colony-stimulating factor promotes wound healing in
      a patient with congenital neutropenia.
AB  - We report a patient with congenital neutropenia or Kostmann's Syndrome who
      suffered many complications after presenting with Clostridium septicum
      enterocolitis, including absence of wound healing. Because of several reports of
      the use of granulocyte colony-stimulating factor (G-CSF) in patients with various
      complications of neutropenia, we treated this patient with recombinant human (rh)
      G-CSF. We found that once rhG-CSF restored neutrophil counts to normal,
      progressive wound healing followed. Thus, rhG-CSF therapy may be useful in
      treating neutropenic patients with wound complications.

PMID- 1380075
TI  - Immunotargeting chemotherapy for AFP-producing pediatric liver cancer using the
      conjugates of anti-AFP antibody and anti-tumor agents.
AB  - The effect of immunotargeting chemotherapy for hepatoblastoma (HB) and
      hepatocellular carcinoma (HCC) following the application of adriamycin (ADM) or
      cis-platinum conjugated with anti-alpha-fetoprotein (AFP) antibody was evaluated
      experimentally and clinically. The conjugate was made from mouse monoclonal
      antihuman AFP antibody linked to ADM or CDDP, with a weight ratio of 2.5:1 via a
      dextran bridge. Experimentally, AFP-producing human HCC transplanted subsequently
      on nude mice was used. A mixture of the antibody and ADM or CDDP was prepared
      with the same ratio. Each drug was injected intraperitoneally, three times at the
      total dose of 14.4 mg/kg as ADM and one time at the dose of 8 mg/kg as CDDP.
      Tumor growth was inhibited significantly in the conjugate group compared with the
      other mixture group, the ADM or CDDP group, and the control group. Clinically,
      the conjugates were administered intraarterially in 4 cases (2 HBs and 2 HCCs)
      and intravenously in one case (1 HB). ADM and CDDP conjugated with anti-AFP
      antibody were used in 2 cases and 3 cases, respectively. Antitumor effects from
      the viewpoint of volume suppression rate showed partial response in 2 cases and
      no change in 3 cases. The immunotargeting chemotherapy using anti-AFP monoclonal
      antibodies may be a promising method for treatment of malignant epithelial liver
      cancer in children.

PMID- 1380076
TI  - High-performance liquid chromatographic analysis of docusate sodium in soft
      gelatin capsules.
AB  - A rapid and simple high-performance liquid chromatographic (HPLC) method for the
      analysis of docusate sodium in soft gelatin capsules was developed with
      progesterone as the internal standard. The method requires a reversed-phase
      column and a paired-ion technique to separate docusate sodium from other
      components. A C22 column was used with a mobile phase of acetonitrile:water
      (70:30) containing 0.005 M tetrabutylammonium phosphate. The flow rate was 1.8
      mL/min, and the effluent was monitored at 214 nm. Docusate sodium and
      progesterone had retention times of 4.5 and 6.8 min, respectively. The proposed
      HPLC method is linear, accurate, and precise. A mean assay value of 99.6% was
      obtained by the proposed method when five samples, each containing a composite of
      10 capsules, were analyzed. The results obtained by the proposed HPLC, tetra-n
      butylammonium iodide titration, and USP XXII HPLC methods are compared.

PMID- 1380077
TI  - Serum-induced sensitization of cyclic AMP accumulation in C62B rat glioma cells.
AB  - Exposure of C62B rat glioma cells to fresh medium containing fetal bovine serum
      induced a sensitization of the subsequent ability of isoproterenol and forskolin
      to stimulate cyclic AMP accumulation, compared to cells exposed to fresh medium
      without serum. Isoproterenol stimulation was typically increased by 2- to 4-fold
      and forskolin stimulation by 3- to 5-fold. Sensitization occurred rapidly, was
      rapidly reversible and appeared to result from an increase in maximal
      stimulation. A commercial preparation of albumin, purified chromatographically so
      as to retain bound lipids and other factors, was able to mimic the effect of
      serum. In contrast to the effects of serum, exposure of cells to phorbol 12
      myristate, 13-acetate induced little or no change in forskolin stimulation but a
      marked desensitization of isoproterenol stimulation that was due primarily to a
      decrease in potency. Neither the protein kinase C inhibitor staurosporine or
      overnight exposure to phorbol 12-myristate, 13-acetate to down-regulate protein
      kinase C prevented serum-induced sensitization. Pertussis toxin almost completely
      blocked serum-induced sensitization, suggesting involvement of a pertussis toxin
      sensitive guanine nucleotide-binding protein in mediating the effects of serum.
      Sensitization was poorly retained in membrane adenylate cyclase assays. Studies
      with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, direct assays
      of cyclic AMP degradation by intact cells and assays of phosphodiesterase
      activity in cell lysates all indicated that degradation of cyclic AMP was
      decreased in serum-pretreated cells. Thus, both increased cyclic AMP synthesis
      and decreased cyclic AMP degradation may contribute to sensitization in these
      cells.

PMID- 1380078
TI  - Comparison of ethanol sensitivity of rat brain kainate, DL-alpha-amino-3-hydroxy
      5-methyl-4-isoxalone proprionic acid and N-methyl-D-aspartate receptors expressed
      in Xenopus oocytes.
AB  - The effect of ethanol (EtOH) on kainate (KA), DL-alpha-amino-3-hydroxy-5-methyl-4
      isoxalone proprionic acid and N-methyl-D-aspartate (NMDA) receptor-operated
      channels was examined electrophysiologically in Xenopus laevis oocytes expressing
      mRNA from rat hippocampus and cerebellum. EtOH (50, 100 mM) inhibited KA-induced
      currents but did not alter the EC50 for KA (approximately 78 microM). For a
      series of n-alcohols, potency for inhibition of KA responses was related to chain
      length. 6,7-dinitroquinoxaline-2,3-dione inhibited maximum KA responses with an
      IC50 of approximately 1 microM; EtOH (50, 100 mM) did not alter the IC50 for 6,7
      dinitroquinoxaline-2,3-dione but did not produce further inhibition of KA-induced
      currents. Despite the apparent noncompetitive inhibition produced by EtOH on KA
      receptor-mediated responses, the EtOH inhibition increased as the KA
      concentration decreased in hippocampal and cerebellar mRNA expressing oocytes.
      This differential inhibition was not due to the different current amplitudes
      stimulated by low vs. high KA concentrations. In contrast, oocytes expressing
      NMDA channels demonstrated a constant percent inhibition by EtOH in the presence
      of 25 to 200 microM NMDA. Altering the extracellular Ca++ concentration did not
      affect the ability of EtOH to inhibit NMDA responses. Maximal NMDA-stimulated
      currents were inhibited by 100 mM EtOH to a lesser extent (31%) in oocytes
      injected with rat cerebellar mRNA than oocytes expressing rat hippocampal mRNA
      (47%), suggesting brain regional differences in NMDA channel inhibition by
      EtOH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380079
TI  - Antinociceptive properties of two alkylating derivatives of morphinone: 14 beta
      (thioglycolamido)-7,8-dihydromorphinone (TAMO) and 14 beta-(bromoacetamido)-7,8
      dihydromorphinone (H2BAMO).
AB  - This study investigated the antinociceptive properties of two alkylating
      derivatives of morphinone, 14 beta-(thioglycolamido)-7,8- dihydromorphinone
      (TAMO) and 14 beta-(bromoacetamido)-7,8-dihydromorphinone (H2BAMO) in the mouse
      tail-flick assay. Intracerebroventricular administration of either TAMO or H2BAMO
      produced short-term antinociception. Both TAMO and H2BAMO were 11.6-fold more
      potent than an i.c.v. administration of morphine. These effects were antagonized
      by the mu-selective antagonist, beta-funaltrexamine, but not by the delta
      selective antagonist, N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH. TAMO pretreatment from
      8 to 48 hr produced a time-related, dose-dependent antagonism of morphine-induced
      antinociception without showing any agonistic effect. Pretreatment with TAMO for
      24 hr antagonized antinociception produced by both H2BAMO and morphine, as well
      as TAMO itself, but not that of the delta-selective agonist [D-Pen2,D
      Pen5]enkephalin (DPDPE) or U50,488, a kappa-selective agonist. In order to
      distinguish this antagonistic effect from cross-tolerance between TAMO and
      morphine, two mu agonists, [D-Ala2,N(Me)Phe4,Gly-ol]enkephalin (DAMGO) and
      H2BAMO, were chosen for comparison. A single i.c.v. pretreatment of DAMGO or
      H2BAMO, at a dose that had equivalent analgesic effects as TAMO, attenuated
      morphine-induced antinociception, reaching a maximal effect at the time of the
      disappearance of agonistic effects of DAMGO and H2BAMO and lasting up to 24 hr.
      Additionally, a 16-hr pretreatment with TAMO, but not DAMGO or H2BAMO, reduced
      the development of physical dependence to morphine at 24 hr after morphine pellet
      implantation. Therefore, this study demonstrated that both TAMO and H2BAMO act as
      mu opioid agonists to produce short-term antinociception.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1380080
TI  - Endothelins constrict guinea pig tracheas by multiple mechanisms.
AB  - When tracheal rings isolated from guinea pigs were treated with endothelins
      (ETs), a dose-dependent constriction was observed and measured isometrically. ET
      potencies were ET-1 = ET-2 greater than ET-3. Dose-response curves of epithelium
      denuded tracheas were shifted to the left by approximately one order of
      magnitude. Lung tissue contained saturable binding sites to 125I-labeled ET-1.
      These binding sites were replaced by ET-1 = ET-2 greater than ET-3. Because the
      airway tissue contained primarily ET-1 as measured by immunoassay after high
      performance liquid chromatography separation, we investigated the mechanism of ET
      1-induced tracheal constriction. Tracheal constriction induced by ET-1 required
      Ca++ in the medium. Because suppression of the contractile response by
      nicardipine and diltiazem was small, Ca++ entry appeared to be gated primarily
      through Ca++ channels rather than via voltage-dependent ones. FPL55712, SC47014A,
      indomethacin and OKY046 suppressed the dose-response curves, suggesting that
      lipid mediators are formed in response to ET-1. Diphenhydramine also altered dose
      response curves, suggesting that histamine release from mast cells was partially
      responsible for the constriction. Pretreatment of tracheas with compound 48/80
      resulted in suppression of the contractile responses. Furthermore, the
      combination of indomethacin, FPL55712 and diphenhydramine gave essentially
      identical effects. Our observations suggest that ET-1 provokes the contractile
      response of guinea pig tracheas not only by direct actions on smooth muscle but
      also by indirect actions through production of chemical mediators in mast cells
      and other inflammatory cells.

PMID- 1380081
TI  - Stereoselective modulation of ryanodine-sensitive calcium channels by the delta
      isomer of hexachlorocyclohexane (delta-HCH).
AB  - delta-Hexachlorocyclohexane (delta-HCH) is shown to be 30-fold more potent as a
      positive inotropic agent with rat atrial strips compared with lindane (gamma
      HCH). Threshold and ED50 values for enhanced contractile force at a pacing
      frequency of 0.5 Hz are less than 1 microM and 2.2 microM for delta-HCH and 40
      microM and 63 microM for gamma-HCH, respectively. Contracture developed in atria
      exposed to greater than 4 microM delta-HCH (ED50 = 11 microM) but not in atria
      exposed to gamma-HCH. Uptake and release of Ca++ measured from actively loaded
      cardiac sarcoplasmic reticulum (SR) vesicles is measured with antipyrylazo III.
      Although delta-HCH (30 microM) decreases Ca(++)-dependent ATPase by 20%, it does
      not significantly alter Ca++ loading in the presence of ruthenium red. Addition
      of delta-HCH (5-50 microM) after loading is complete causes rapid, dose-dependent
      release of Ca++ from SR. Ca++ release induced by delta-HCH is markedly
      stereoselective. Compared with gamma-HCH (50 microM), delta-HCH (50 microM)
      induces a nearly 20-fold higher initial rate of Ca++ release (4.3 nmol of
      Ca++/mg/sec). Studies with [3H]ryanodine demonstrate that delta-HCH sharply
      inhibits Ca(++)- or daunorubicin-activated radioligand binding (IC50 = 37 and 25
      microM, respectively, logit slope = 2). Inhibition of [3H]ryanodine-binding by
      delta-HCH is stereoselective inasmuch as IC50 values for alpha, beta and gamma
      isomers are greater than 100 microM. The delta-HCH modified Ca++ channel appears
      to proceed by a noncompetitive mechanism (reducing Bmax in equilibrium
      experiments) with respect to the conformationally sensitive binding site for
      [3H]ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380082
TI  - Stimulation by risperidone of rat prolactin secretion in vivo and in cultured
      pituitary cells in vitro.
AB  - Risperidone, a new antipsychotic agent which antagonizes both 5-hydroxytryptamine
      2 (5-HT2) and dopamine-2 (D2) receptors, was evaluated for its effects on
      prolactin release. One hr after either p.o. or i.p. dosing, risperidone was 3 to
      5 times more potent than the classical D2 receptor antagonist haloperidol in
      stimulating rat prolactin levels in vivo. This result was unexpected because
      haloperidol is a more potent D2 receptor antagonist than risperidone in vitro.
      Mechanisms which might explain these observations were investigated. Compared to
      haloperidol, risperidone was 0.34 (95% confidence interval: 0.23, 0.48) times as
      potent in reversing the suppression by dopamine of rat anterior pituitary cell
      prolactin release in vitro, which is consistent with the compounds' striatal D2
      receptor binding potencies in vitro. Administration of ketanserin, a 5-HT2
      receptor antagonist, along with haloperidol did not modify haloperidol's activity
      on either in vitro pituitary cell prolactin release (up to 1000 nM ketanserin) or
      in vivo prolactin concentrations (5 mg/kg ketanserin, i.p.). In vitro incubation
      of haloperidol and risperidone with a liver homogenate supernatant (S-9) led to
      extensive (greater than 86%) metabolism of each compound. S-9 treatment abolished
      haloperidol's effects on pituitary cell prolactin release. Risperidone's ability
      to increase prolactin release was unchanged after S-9 treatment, and 9-hydroxy
      risperidone, identified as a major metabolite in the S-9 conditioned media, was
      equipotent to risperidone in modulating prolactin release in vitro.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380083
TI  - N-methyl-D-aspartate receptor antagonism alters substance P and met5-enkephalin
      biosynthesis in neurons of the rat striatum.
AB  - A reduction of striatal excitatory amino acids or of corticostriatal axons alters
      substance P (SP) and met5-enkephalin (ME) biosynthesis in striatal neurons of the
      rat. To determine the role of the N-methyl-D-aspartate (NMDA) receptor in this
      effect, adult rats were treated acutely with a single i.c.v. injection or
      chronically by 7 days of continuous infusion of an NMDA antagonist. The striatal
      content of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA was assessed by
      in situ hybridization histochemistry while the content of SP and ME in,
      respectively, the substantia nigra and globus pallidus was measured by
      quantitative radioimmunocytochemistry. Eight hours after a single injection,
      striatal PPT and PPE mRNA levels were significantly reduced. At 24 hr, the level
      of PPE had returned to control level whereas that of PPT mRNA remained depressed.
      Nigral SP and pallidal ME levels were not acutely changed. Chronically, the
      effect of NMDA antagonist at low doses was to increase the striatal content of
      PPE mRNA. However, at higher concentrations, the effect was to reduce in a dose
      dependent manner the striatal content of PPT and PPE mRNA and the level of
      pallidal ME. The nigral level of SP did not change significantly at any dose. The
      results suggest that excitatory amino acid transmission mediated by the NMDA
      receptor serves as a tonic signal to stimulate neuroactive peptide biosynthesis.

PMID- 1380084
TI  - Hemi-gap-junction channels in solitary horizontal cells of the catfish retina.
AB  - 1. Solitary horizontal cells were isolated from catfish retinas and their
      membrane current was recorded with a whole-cell voltage clamp. Reducing the
      extracellular Ca2+ concentration produced a current that could be suppressed by
      dopamine. This Ca(2+)- and dopamine-sensitive current is hereafter termed I
      gamma. The voltage dependence, cytoplasmic regulation, and permeability of the I
      gamma channel suggest that it is half of a gap-junction channel. 2. I gamma was
      voltage and time dependent. In the steady state, the current-voltage relation
      displayed outward rectification at voltages more depolarized than 0 mV and a
      negative resistance region at voltages more hyperpolarized than -15 mV. The
      reversal potential was 3.3 +/- 1.5 mV when NaCl was the predominant extracellular
      salt and potassium-D-aspartate was the predominant intracellular salt. 3. The
      size of I gamma depended on the extracellular Ca2+ concentration. I gamma was
      maximal at external Ca2+ concentrations below 10 microM, half-maximal at 220
      microM-Ca2+, and reduced to less than 4% of its maximum amplitude at external
      Ca2+ concentrations above 1 mM. Increasing the extracellular Ca2+ concentration
      reduced the amplitude of I gamma without changing the shape of the current
      voltage relation or the kinetics of inactivation. Thus, rectification does not
      result from a voltage-dependent block by extracellular Ca2+. 4. Patches of cell
      membrane were voltage clamped in both the cell-attached and excised-patch
      configurations. In the cell-attached configuration, the addition of dopamine to
      the solution outside the patch pipette blocked the opening of channels within the
      membrane patch. Thus, dopamine closes I gamma channels by initiating an
      intracellular messenger cascade. In the excised-patch configuration, a maximum
      conductance of 145 pS was measured while Cs+ and tetraethylammonium+ (TEA+) were
      the only monovalent cations on both sides of the membrane. 5. The ability of
      dopamine to suppress I gamma was blocked by introducing an inhibitor of the
      cyclic AMP-dependent protein kinase, PKI5-24, into the cytoplasm. Thus, the
      action of dopamine is mediated by a pathway that includes the activation of a
      cyclic AMP-dependent kinase. 6. I gamma was suppressed by nitroprusside, an agent
      which activates guanylate cyclase and increases the intracellular cyclic GMP
      concentration. The effect of nitroprusside was not altered by the intracellular
      application of PKI5-24. Thus, nitroprusside suppresses I gamma through a pathway
      that does not include the activation of a cyclic AMP-dependent kinase.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1380085
TI  - Modulation of potassium channels in intact human T lymphocytes.
AB  - 1. A voltage-dependent K+ channel called the 'n' type (for 'normal') is the most
      prevalent ion channel found in whole-cell recordings from T lymphocytes. In whole
      cell patch-clamp recordings activity of the n-type channel is affected by
      mitogenic agents, pH, Ca2+ and temperature but not by cyclic nucleotides. Because
      channel properties and regulation can depend on cytoplasmic components we sought
      to reassess the properties of K+ channels in intact, normal human T lymphocytes
      using cell-attached, patch-clamp recordings. In the present study, we show that
      the predominant K+ channel in resting, intact cells is the n type and is affected
      by voltage, temperature and Ca2+ in ways similar to the disrupted cell. Moreover,
      K+ channels are activated by agents that raise cyclic AMP in intact cells. 2. In
      cell-attached recordings, we found voltage-activated K+ channels in about 60% of
      patches at room temperature. The channel was K+ selective as judged from the
      reversal potential under different Ka(+)-K+ gradients and at different resting
      membrane potentials. Some patches were subsequently excised and the selectivity
      further confirmed. The current-voltage relation was inwardly rectifying under
      symmetrical K+ concentrations and had a slope conductance of 9.4 pS at 50 mV
      depolarized and 23.8 pS at 50 mV hyperpolarized from the resting potential. From
      the reversal potentials under various conditions the cell resting potential was 
      51 +/- 1 mV in normal NaCl saline and about 0 mV when the bath contained 150 mM
      KCl saline. Two other types of K+ channel were seen in resting, intact cells, but
      were much less common (less than 5% and 11% of patches). A large-conductance K+
      channel was seen in less than 1% of inside-out patches. 3. The predominant K+
      channel in intact, resting T lymphocytes was confirmed as the n type underlying
      the whole-cell K+ current evoked by voltage steps. In cell-attached patches there
      was a low, steady-state level of activity at the resting potential but activity
      was greatly increased by depolarizing voltage jumps. Steady-state inactivation
      could be removed by a hyperpolarizing pre-pulse. Ensemble currents constructed by
      summing channel openings during repeated voltage jumps showed sigmoid kinetics of
      current activation and a monoexponential decay phase. These kinetics were well
      fitted by a Hodgkin-Huxley-type n4j kinetic model with time constants very
      similar to the whole-cell current of disrupted cells. Moreover, the kinetics
      depended on the external K+ concentration as previous research has
      shown.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380086
TI  - Release of intracellular calcium and modulation of membrane currents by caffeine
      in bull-frog sympathetic neurones.
AB  - 1. Calcium release and sequestration were studied in whole-cell voltage-clamped
      bull-frog sympathetic neurones by image analysis of Fura-2 signals. 2.
      Application of caffeine (10 mM) to cells voltage clamped at -38 mV caused a rapid
      increase in intracellular calcium concentration ([Ca2+]i) to a mean value of 352
      +/- 33 nM, which activated an outward current. In the continued presence of
      caffeine the rise in [Ca2+]i slowly declined to a sustained plateau of 196 +/- 20
      nM (112 nM above control levels), while the outward current rapidly decayed. Peak
      calcium release was highest at the edge of the cell. 3. The caffeine-evoked
      intracellular calcium increase was reduced by two inhibitors of calcium-induced
      calcium release, ryanodine and procaine. The residual non-suppressible increase
      in [Ca2+]i may indicate that caffeine can release calcium from two
      pharmacologically distinct intracellular stores. 4. Inhibition of the caffeine
      evoked release of calcium by ryanodine was both concentration and 'use dependent'
      so that the full inhibitory effect was only observed when caffeine was applied
      for the second time in the presence of ryanodine. In contrast, the action of
      procaine did not show any 'use dependence' and unlike ryanodine was fully
      reversible. 5. The outward current was sensitive to blockers of the large
      conductance calcium-activated potassium current, Ic. Analysis of variance from
      this current indicated that it arose at least partly from summation of
      spontaneous miniature outward currents. 6. The magnitude and duration of calcium
      release by caffeine was dependent on the resting level of intracellular calcium
      and the caffeine exposure time. This, together with the pharmacology of the
      release, suggests that caffeine increases intracellular calcium by sensitizing
      calcium-induced calcium release. 7. The evoked [Ca2+]i increase was enhanced in
      amplitude by intracellular application of Ruthenium Red. This effect was mimicked
      by extracellular application of the mitochondrial uncoupler carbonyl cyanide p
      trifluoromethoxyphenyl-hydrazone (FCCP) but not by internal application of FCCP
      or other inhibitors of mitochondrial Ca2+ uptake. This suggests that the evoked
      increase in [Ca2+]i is predominantly buffered by a Ruthenium Red-sensitive
      sequestration process which is not mitochondrial.

PMID- 1380087
TI  - Involvement of sarcoplasmic reticulum 'Ca2+ release channels' in excitation
      contraction coupling in vertebrate skeletal muscle.
AB  - 1. Pharmacological blockers of calcium-induced calcium release from isolated
      skeletal sarcoplasmic reticulum (SR) vesicles have been introduced into frog
      skeletal muscle fibres to determine their effects on excitation-contraction
      coupling. 2. Among the blockers tested, Ruthenium Red, neomycin, gentamicin and 9
      aminoacridine inhibited the SR Ca2+ release associated with excitation
      contraction (E-C) coupling as much as they inhibited caffeine potentiation of
      that release. Protamine, certain of its derivatives, and spermine were
      ineffective in both in situ tests. 3. Alternative sites of polyamine action on
      the contractile proteins, SR Ca2+ uptake or charge movements were ruled out. 4.
      All polyamines tested required considerably higher concentrations to inhibit
      excitation-contraction coupling than to block Ca2+ release from isolated SR
      vesicles. 5. The quantitative pharmacological difference in sensitivity between
      isolated and intact systems serves as a reminder that results on isolated systems
      cannot generally be used to predict results of the same substances on more
      physiological systems. 6. Since caffeine is known to open the SR 'Ca2+ release
      channels' (the ryanodine receptors that mediate Ca(2+)-induced Ca2+ release), the
      equal effectiveness of these blockers at inhibiting excitation-contraction (E-C)
      coupling and its potentiation by caffeine suggests that the SR 'Ca2+ release
      channels' are indeed involved in excitation-concentration coupling in skeletal
      muscle, although the results do not indicate how the channel is gated open during
      E-C coupling.

PMID- 1380088
TI  - Morphometric study of nucleolar organizer regions in human oral normal mucosa,
      papilloma and squamous cell carcinoma.
AB  - A morphometric study of nucleolar organizer regions (NOR) was performed to
      analyze their distribution, volume, number and shape in the different strata of
      human normal oral mucosa epithelium and papilloma and in squamous cell carcinoma
      employing microphotographs of silver-stained paraffin sections. The different NOR
      related parameters evidenced significant differences between normal mucosa,
      papilloma and squamous cell carcinoma. The functional polarity of normal mucosa
      epithelium and of papilloma is also evidenced in terms of NOR-related parameters.
      The discriminative value of certain NOR parameters was demonstrated.

PMID- 1380089
TI  - Ion selectivity of colicin E1: II. Permeability to organic cations.
AB  - Channels formed by colicin E1 in planar lipid bilayers have large diameters and
      conduct both cations and anions. The rates at which ions are transported,
      however, are relatively slow, and the relative anion-to-cation selectivity is
      modulated over a wide range by the pH of the bathing solutions. We have examined
      the permeability of these channels to cationic probes having a variety of sizes,
      shapes, and charge distributions. All of the monovalent probes were found to be
      permeant, establishing a minimum diameter at the narrowest part of the pore of
      approximately 9 A. In contrast to this behavior, all of the polyvalent organic
      cations were shown to be impermeant. This simple exclusionary rule is interpreted
      as evidence that, when steric restrictions require partial dehydration of an ion,
      the structure of the channel is able to provide a substitute electrostatic
      environment for only one charged group at time.

PMID- 1380090
TI  - Cl- channels in basolateral renal medullary vesicles: V. Comparison of
      basolateral mTALH Cl- channels with apical Cl- channels from jejunum and trachea.
AB  - Cl- channels from basolaterally-enriched rabbit outer renal medullary membranes
      are activated either by increases in intracellular Cl- activity or by
      intracellular protein kinase A (PKA). Phosphorylation by PKA, however, is not
      obligatory for channel activity since channels can be activated by intracellular
      Cl- in the absence of PKA. The PKA requirement for activation of Cl- channels in
      certain secretory epithelia is, in contrast, obligatory. In the present studies,
      we examined the effects of PKA and intracellular Cl- concentrations on the
      properties of Cl- channels obtained either from basolaterally-enriched vesicles
      derived from highly purified suspensions of mouse medullary thick ascending limb
      (mTALH) segments, or from apical membrane vesicles obtained from two secretory
      epithelia, bovine trachea and rabbit small intestine. Our results indicate that
      the Cl- channels from mTALH suspensions were virtually identical to those
      previously described from rabbit outer renal medulla. In particular, an increase
      in intracellular (trans) Cl- concentration from 2 to 50 mM increased both channel
      activity (Po) and channel conductance (gCl, pS). Likewise, trans PKA increased
      mTALH Cl- channel activity by increasing the activity of individual channels when
      the trans solutions were 2 mM Cl. Under the latter circumstance, PKA did not
      activate quiescent channels, nor did it affect gCl. Moreover, when mTALH Cl-
      channels were inactivated by reducing cis Cl- concentrations to 50 mM, cis PKA
      addition did not affect Po. These results are consistent with the view that these
      Cl- channels originated from basolateral membranes of the mTALH. Cl- channels
      from apical vesicles from trachea and small intestine were completely insensitive
      to alterations in trans Cl- concentrations and demonstrated markedly different
      responses to PKA. In the absence of PKA, tracheal Cl- channels inactivated
      spontaneously after a mean time of 8 min; addition of PKA to trans solutions
      reactivated these channels. The intestinal Cl- channels did not inactivate with
      time. Trans PKA addition activated new channels with no effect on basal channel
      activity. Thus the regulation of Cl- channel activity by both intracellular Cl-
      and by PKA differ in basolateral mTALH Cl- channels compared to apical Cl-
      channels from either the tracheal or small intestine.

PMID- 1380091
TI  - Modification of gating of an airway epithelial chloride channel by 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB).
AB  - 5-Nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) has been shown to produce a
      reduction in channel open probability in a number of epithelial chloride
      channels. We have investigated its action on a calcium-dependent airway
      epithelial chloride channel, which shows voltage-dependent gating following
      incorporation into planar phospholipid bilayers. Since the channel demonstrates a
      distinct subconductance state at approximately one-third of the fully open level,
      both 50 and 20% threshold analysis (TA) have been used to describe channel
      kinetics. Lifetime analysis using 50% TA in the absence of NPPB showed that two
      open and three closed lifetimes provided the optimal fit. Similar analysis using
      20% TA required only two closed lifetimes and allowed for tentative assignment of
      tau values to either substate or fully closed events. NPPB (10-100 microM)
      produced a concentration-related shift of the normal voltage dependence of
      gating, with more negative holding potentials being required to produce a given
      channel open probability than in the absence of NPPB. Ten microM NPPB produced a
      similar shift in lifetime values. However, addition of 50 microM NPPB produced a
      unique, single open lifetime. No evidence was found for NPPB acting as a direct
      voltage-dependent blocker of chloride conductance.

PMID- 1380092
TI  - Localization of epitopes for antibodies that differentially label sodium sodium
      channels in skeletal muscle surface and T-tubular membranes.
AB  - We previously characterized two monoclonal antibodies, A/B2 and L/D3, that bind
      to the amino-terminus of the sodium channel but produce distinct
      immunocytochemical patterns in innervated adult skeletal muscle. Because these
      findings suggested the presence of several channel isoforms, we sought to define
      the epitopes for each antibody. Five peptides encompassing the amino-terminal 126
      residues of the adult skeletal muscle sodium channel were synthesized and tested
      by radioimmunoassay against each antibody. Both monoclonals bound only to a
      peptide comprising residues 1-30 (I1-30). A nested set of peptides within this
      region was then synthesized and used to compete for antibody binding to I1-30.
      L/D3 binding was quantitatively inhibited by oligopeptides 1-30, 7-30, 13-30, and
      19-30 but not 25-30, while binding of A/B2 was blocked only by the intact I1-30
      peptide. This data implies that the epitope for L/D3 lies within residues 19-25
      while the epitope for A/B2 is contained within residues 1-6. These tentative
      epitope localizations were confirmed using both proteolytic cleavage of I1-30 and
      immunoreactivity of a peptide corresponding to residues 1-12 with A/B2 but not
      L/D3. Therefore, epitopes for each monoclonal antibody are present in the SkM-1
      sequence and are in close proximity in the amino-terminus of the protein. Their
      characteristic immunocytochemical labeling patterns may reflect differing
      accessibility of the epitopes in various membrane environments.

PMID- 1380093
TI  - Soluble glycoprotein D blocks herpes simplex virus type 1 infection of rat eyes.
AB  - Herpes simplex virus type 1 (HSV-1) ocular infection in rats was blocked by
      treating the eyes with UV-inactivated virions containing glycoprotein D (gD)
      prior to ocular challenge. In contrast, rats treated with UV-inactivated virions
      lacking gD were not protected. A soluble, truncated form of HSV-2 gD (gD-2t) also
      protected against ocular infection. Treatment with gD-2t not only reduced
      mortality but also restricted progression of pathology and reduced the amount of
      viral antigen in the cornea. Host antibody or alpha/beta interferon responses to
      the gD-2t treatment were not detected. These results are similar to those
      observed in cell culture (D. C. Johnson, R. L. Burke, and T. Gregory, J. Virol.
      64:2569-2576, 1990). The in vivo effect of exogenous gD is consistent with
      blocking of a cell surface gD receptor or with an inhibitory interaction of gD
      with virions.

PMID- 1380094
TI  - Examination of sera from human immunodeficiency virus type 1 (HIV-1)-infected
      individuals for antibodies reactive with peptides corresponding to the principal
      neutralizing determinant of HIV-1 gp120 and for in vitro neutralizing activity.
AB  - Sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals from
      the United States and Tanzania were examined for antibody reactivity to four
      synthetic peptides which corresponded to the principal neutralizing determinant
      from the V3 region of HIV-1 gp120. We observed that the majority of sera from
      both countries contained antibodies reactive with a V3 peptide whose sequence is
      based on that of the HIV-1 MN isolate. We were unable to establish a relationship
      between the presence of V3-reactive antibodies, as measured by enzyme-linked
      immunosorbent assay and neutralization of homologous HIV-1 isolates, in sera from
      either the United States or Tanzania. We observed that some sera which contained
      high antibody titers to the V3 peptides failed to neutralize HIV-1, while others
      with no antibody reactivity to the panel of V3 peptides exhibited in vitro
      neutralizing activity. These results suggest that neutralizing epitopes exist
      outside the V3 loop and that the presence of V3-reactive antibodies in sera does
      not imply in vitro neutralization of the homologous HIV-1 isolate. In addition,
      it appears that the V3 loop may consist of both neutralizing and nonneutralizing
      epitopes. The identification of neutralizing as well as nonneutralizing epitopes
      will be important for the design of potential HIV-1 vaccines.

PMID- 1380095
TI  - Interactions of polyomavirus middle T with the SH2 domains of the pp85 subunit of
      phosphatidylinositol-3-kinase.
AB  - The binding of phosphatidylinositol-3-kinase to the polyomavirus middle T antigen
      is facilitated by tyrosine phosphorylation of middle T on residue 315. The pp85
      subunit of phosphatidylinositol-3-kinase contains two SH2 domains, one in the
      middle of the molecule and one at the C terminus. When assayed by blotting with
      phosphorylated middle T, the more N-terminal SH2 domain is responsible for
      binding to middle T. When assayed in solution with glutathione S transferase
      fusions, both SH2s are capable of binding phosphorylated middle T. While both SH2
      fusions can compete with intact pp85 for binding to middle T, the C-terminal SH2
      is the more efficient of the two. Interaction between pp85 or its SH2 domains and
      middle T can be blocked by a synthetic peptide comprising the tyrosine
      phosphorylation sequence around middle T residue 315. Despite the fact that
      middle T can interact with both SH2s, these domains are not equivalent. Only the
      C-terminal SH2-middle T interaction was blocked by anti-SH2 antibody; the two SH2
      fusions also interact with different cellular proteins.

PMID- 1380096
TI  - Group C rotavirus requires sialic acid for erythrocyte and cell receptor binding.
AB  - Current immunological and biochemical information regarding the hemagglutinin and
      virus-cell interactions of rotavirus is obtained exclusively from studies with
      group A rotaviruses. In this study, I report that the immunologically and
      genetically distinct group C rotavirus also possesses a hemagglutinin. The viral
      hemagglutinin was identified on a cultivable porcine group C rotavirus strain
      (strain AmC-1) by using agglutinated human and guinea pig erythrocytes.
      Neuraminidase treatment of fresh human erythrocytes or blocking with glycophorin
      A or fetuin prevented hemagglutination. Infection of swine testicular cells with
      group C AmC-1 virus was also prevented by glycophorin A, fetuin, and
      neuraminidase treatment, suggesting that sialic acid constitutes an essential
      part of the cell receptor.

PMID- 1380097
TI  - Purification of immature cores of mouse mammary tumor virus and
      immunolocalization of protein domains.
AB  - The immature capsids of the mouse mammary tumor virus (MMTV), known as
      intracytoplasmic A particles, have been isolated from murine L1210 leukemia
      cells. The diameter of the isolated particles was 80 nm as determined by negative
      staining. Two polypeptides of 77 and 110 kDa were found to be their major
      polypeptide components, in agreement with the expected sizes of the Gag and Gag
      Pro precursor polypeptides of the mature MMTV proteins. Both polypeptides were
      recognized by antibodies directed toward the matrix (p10) and capsid (p27)
      proteins of MMTV. Immunogold labeling of p10 on isolated A particles, visualized
      by negative staining, showed that this protein is located at the surface of the
      immature capsids, whereas p27 can be detected only in broken or disrupted
      particles, suggesting that it has an internal location. These observations were
      confirmed by immunolabeling of both proteins on thin sections of A particle
      producing cells. In addition, the viral protease had a more internal position
      than p27. Since the sequential order of the viral proteins in the Gag precursor
      is p10-pp21-p27-p14 and that in Gag-Pro is p10-pp21-p27-p30-protease, our results
      demonstrate the radial organization of the polypeptide precursors forming the
      intracytoplasmic A particles.

PMID- 1380098
TI  - Persistence of azidothymidine-resistant human immunodeficiency virus type 1 RNA
      genotypes in posttreatment sera.
AB  - The rate of reversion from azidothymidine (zidovudine; AZT) resistance was
      studied by direct sequencing of human immunodeficiency virus type 1 (HIV-1)
      virion RNA in sera from four patients who discontinued long-term treatment.
      Before cessation of treatment, all four patients harbored HIV-1 with multiple
      mutations reported to confer AZT resistance. In three patients, slow reversions
      of these mutations starting after 9, 9, and 18 months were detected. The slow
      reversions indicate that AZT-resistant HIV-1 variants are likely to have an
      unaltered replicative capacity and pathogenic potential. Furthermore, there were
      discrepancies between the in vivo RNA sequences and the sequences of virus
      isolates, indicating that the isolation procedure may select for
      nonrepresentative virus variants.

PMID- 1380099
TI  - Discontinuous, conserved neutralization epitopes overlapping the CD4-binding
      region of human immunodeficiency virus type 1 gp120 envelope glycoprotein.
AB  - Monoclonal antibodies have been isolated from human immunodeficiency virus type 1
      (HIV-1)-infected patients that recognize discontinuous epitopes on the gp120
      envelope glycoprotein, that block gp120 interaction with the CD4 receptor, and
      that neutralize a variety of HIV-1 isolates. Using a panel of HIV-1 gp120
      mutants, we identified amino acids important for precipitation of the gp120
      glycoprotein by three different monoclonal antibodies with these properties.
      These amino acids are located within seven discontinuous, conserved regions of
      the gp120 glycoprotein, four of which overlap those regions previously shown to
      be important for CD4 recognition. The pattern of sensitivity to amino acid change
      in these seven regions differed for each antibody and also differed from that of
      the CD4 glycoprotein. These results indicate that the CD4 receptor and this group
      of broadly neutralizing antibodies recognize distinct but overlapping gp120
      determinants.

PMID- 1380100
TI  - [Inhibitory effect of somatostatin analog, SMS 201-995, on exocrine secretion
      from isolated rat pancreatic acini].
AB  - In vitro effect of somatostatin analog, SMS 201-995 (SMS), on pancreatic exocrine
      secretion was investigated using isolated rat pancreatic acini. SMS had no effect
      on basal, cholecystokinin octapeptide (CCK-8)- or secretin-stimulated amylase
      release. SMS inhibited pancreatic amylase release in response to simultaneous
      stimulation with secretin and CCK-8 in a dose-dependent manner. Significant
      inhibition was observed with 10 nM SMS and maximal inhibition with 0.1-1 microM
      SMS. Amylase release in response to the combination of 100 pM CCK-8, 1 nM
      secretin and 0.1-1 microM SMS was similar to that to 100 pM CCK-8 alone. Secretin
      significantly increased acinar cell cAMP content. SMS partially inhibited an
      increase in cAMP content induced by secretin. The present study has demonstrated,
      therefore, that SMS directly inhibits the potentiating effect of secretin on
      exocrine secretion in part by inhibiting an increase in secretin-induced cAMP
      accumulation in rat pancreatic acinar cells.

PMID- 1380101
TI  - [Immunohistochemical study of cell adhesion molecule and its receptor in
      hepatocellular carcinoma].

PMID- 1380102
TI  - [Minimally invasive surgery].

PMID- 1380103
TI  - Indirect measurement of lymphatic absorption in CAPD patients is not influenced
      by trapping.
AB  - The disappearance rate of intraperitoneally administered macromolecules is often
      used to calculate lymphatic absorption during CAPD. The possible contribution of
      local accumulation (trapping) of such solutes in the tissues surrounding the
      peritoneal cavity, leading to overestimation of lymphatic flow, was investigated
      in eight CAPD patients. They were studied twice during a four hour dwell, glucose
      1.36%, to which polydisperse neutral dextran 70 1 g/liter had been added for
      measurement of lymphatic flow. After the test on day 1 dextran 130 mg/kg was
      given intravenously and also dextran 1 g/liter was added to every following
      dialysis bag until the second test on day 3. This was done to saturate the
      tissues surrounding the peritoneal cavity and thereby to create a steady state
      condition. In one patient the dextran administration was continued until a third
      study was done on day 5. Dextran in serum during day 3 was 1.3 +/- 0.5 g/liter
      (mean +/- SD). No difference in peritoneal clearance of dextran was found between
      day 1 and day 3 (1.11 +/- 0.56 versus 0.97 +/- 0.41 ml/min). Also no difference
      was found between day 1 (0.32), day 3 (0.62), and day 5 (0.42 ml/min). Trapping
      would have influenced the first but not the second test, as the second time all
      tissues were saturated with dextran. As the dextran absorption rate remained the
      same, this indicates that trapping is of no importance and that lymphatic
      absorption can be measured by the disappearance of a macromolecular marker.

PMID- 1380104
TI  - Experimental chronic renal ischemia: morphologic and immunologic studies.
AB  - Although unilateral clamping of the renal artery to induce chronic ischemia of
      the kidney tissue has been utilized in several animal species, the resultant
      morphologic, ultrastructural and immunologic changes have never been well
      characterized. Moreover, the pathogenesis of these changes, as well as their
      roles in causing or facilitating the development of chronic tubulointerstitial
      nephritis have not been known. To examine some of these issues, male Sprague
      Dawley rats were subjected to unilateral stenosis of the left main renal artery
      for 28 days. Stenotic and contralateral kidneys of experimental animals and
      kidneys from sham-operated controls were subjected to: (1) light microscopic,
      electron microscopic and immunofluorescent studies; (2) morphometric quantitation
      of the structural changes; (3) staining for actin, epithelial membrane antigen,
      keratin, and vimentin by immunoperoxidase technique; (4) staining for complex
      glycoproteins by a panel of 13 lectins; and (5) phenotyping and quantitation of
      the interstitial inflammatory infiltrates by monoclonal antibodies, using
      immunoperoxidase technique. The results reveal that: (1) The ischemic kidney
      tissue displays marked tubulointerstitial damages including abundant interstitial
      chronic inflammatory infiltrates, with good preservation of glomerular structure,
      which is consistent with the standard criteria of chronic tubulointerstitial
      nephritis. (2) The antigenic profile of the ischemic tubular epithelium displayed
      marked alterations including a neo-expression of vimentin and keratin, as well as
      a loss of endogenous avidin binding activity, Ia antigen and several complex
      surface glycoproteins detectable by lectins. (3) Neither electron dense deposits
      nor immunoglobulins are detectable in the kidneys from experimental or control
      animals. (4) Tubulitis, defined as infiltration of tubular epithelium by
      inflammatory cells, was present in up to 42.2% of tubular cross sections of the
      ischemic kidneys. (5) The interstitial inflammatory infiltrates were composed of
      B lymphocytes, T helper lymphocytes, and macrophages whereas the T non-helper
      lymphocytes were scanty, a phenotypic pattern similar to that of several other
      experimental rat models of chronic tubulointerstitial nephritis. It is concluded
      that: (1) In the Sprague-Dawley rats, ischemia alone can cause a constellation of
      changes fulfilling the accepted features of chronic interstitial nephritis; (2)
      ischemia alters the antigenic profile of the tubular epithelium and thereby may
      initiate a cell mediated immune response, accounting for the observed tubulitis
      and interstitial inflammation; and (3) ischemia may well be the final common
      pathway for chronic tubulointerstitial nephritis of diverse etiologies.

PMID- 1380105
TI  - Abatement of bleomycin-induced increases in vascular permeability, inflammatory
      cell infiltration, and fibrotic lesions in hamster lungs by combined treatment
      with taurine and niacin.
AB  - BACKGROUND: The bleomycin (BL) hamster model of interstitial pulmonary fibrosis
      has been widely used to study the pathogenesis of interstitial pulmonary fibrosis
      and to screen potentially desirable antifibrotic agents. We have recently shown
      that taurine and niacin in combination, diminished BL-induced increases in lung
      lipid peroxidation and hydroxyproline content in hamsters. In the present study,
      we have evaluated the effects of taurine and niacin on the bronchoalveolar lavage
      (BAL) cells, and morphologic and morphometric features of the lung in the same
      model of pulmonary fibrosis. EXPERIMENTAL DESIGN: The hamsters were divided into
      4 groups: saline; taurine + niacin + saline; BL; and taurine + niacin + BL.
      Treatment of taurine and niacin began 2 days before the first intratracheal
      instillation of saline or BL and thereafter daily throughout the study for
      taurine + niacin + saline and taurine + niacin + BL groups. Hamsters received BL
      or saline in three consecutive doses at weekly intervals by intratracheal route.
      Twenty days after the last intratracheal instillation, the hamsters were
      sacrificed for various studies. RESULTS: Combined treatment with taurine and
      niacin suppressed BL-induced inflammation and almost completely abrogated
      pulmonary fibrosis in hamsters. Two independent studies showed that taurine and
      niacin in combination significantly reduced BL-induced increases in
      bronchoalveolar inflammatory cell counts, protein content, and acid phosphatase
      activity. By both light and electron microscopy, the lungs of hamsters treated
      with BL and taurine and niacin had much fewer inflammatory cells, less epithelial
      necrosis and collagen deposition than hamsters treated with BL alone.
      CONCLUSIONS: The results of this investigation suggest that combined treatment
      with taurine and niacin is effective against the development of lung fibrosis in
      the BL-hamster model and offers a novel therapeutic modality in the prevention of
      the fibrotic processes.

PMID- 1380106
TI  - Hemoglobin-acetaldehyde adducts in human alcohol abusers.
AB  - BACKGROUND: Previous observations have indicated that acetaldehyde can bind
      irreversibly to proteins in vitro, yielding immunogenic determinants, which can
      stimulate production of antibodies against the acetaldehyde adducts. EXPERIMENTAL
      DESIGN: We have developed sensitive two-site enzyme-linked immunosorbent assays
      for measurement of hemoglobin-acetaldehyde adducts. These adducts were measured
      from the red blood cells of 169 alcohol abusers, 66 social drinkers, 18
      abstainers, and 73 hospitalized control patients. RESULTS: While the
      immunoreactive acetaldehyde adducts were found to be increased in 50% of the
      alcohol abusers (p less than 0.01), 24% of the social drinkers (p less than 0.05)
      also exceeded the reference interval obtained from the abstaining controls.
      Adducts were also increased in 17 (23%) hospitalized controls, seven of whom
      could retrospectively be verified as heavy drinkers. Upon abstinence from
      ethanol, the adducts decreased during a period of 1-3 weeks. CONCLUSIONS: The
      studies indicate that acetaldehyde adducts are frequently elevated in the
      erythrocytes of human alcohol consumers. Measurements of such adducts may prove
      to be valuable in the early identification of excessive alcohol consumption and
      of hazardous social drinking and in the comprehensive assessment and treatment of
      patients with alcohol-related diseases.

PMID- 1380107
TI  - Cystic fibrosis: a disease caused by a single defect in salt-transporting
      epithelial cells.

PMID- 1380108
TI  - Propylene glycol as a vehicle for percutaneous absorption of therapeutic agents.
AB  - Propylene glycol (PG) was evaluated as a vehicle for the in vivo percutaneous
      absorption of the hydrochloride salts of desipramine, nortriptyline,
      procainamide, and N-acetyl-procainamide. Each drug was administered topically to
      hairless (hr-1/hr-1) mice in water and in aqueous 10% and 50% PG. Mean drug
      concentrations in blood, brain, heart, liver, and lung were measured by high
      pressure liquid chromatography after either two or three hours of topical
      absorption. The presence of PG generally enhanced the absorption of each drug,
      and the degree of enhancement appeared to be related to the percentage of PG in
      the dosing solution.

PMID- 1380109
TI  - A simplified method for the preparation of tetanus toxin binding fragment for
      neurobiology.
AB  - The non-toxic binding fragment of tetanus toxin (fragment C) binds avidly to
      neural tissue and has a growing number of neurobiological uses. Its current
      utility is limited by both its high commercial cost and the complex procedure for
      its preparation requiring highly purified tetanus toxin. We have developed a
      short procedure which prepares fragments of tetanus toxin from crude C. tetani
      extracts. The resultant proteins are atoxic with molecular sizes and
      immunological properties closely resembling fragment C. These proteins undergo
      retrograde axonal and apparent transneuronal transport in a fashion similar to
      fragment C.

PMID- 1380111
TI  - Inhibition of contact allergy reactions by topical FK506.

PMID- 1380110
TI  - Calcitonin gene-related peptide potentiates substance P-induced plasma
      extravasation in the rat trachea.
AB  - Antidromic stimulation of vagal sensory nerves is known to produce plasma
      extravasation in the rat trachea. This neurogenic inflammation is thought to be
      mediated by substance P or other tachykinins released from sensory nerve endings.
      We sought to determine whether calcitonin gene-related peptide (CGRP), which is
      also released from sensory nerve endings, can potentiate substance P-induced
      plasma extravasation in the rat trachea. To accomplish this, we measured the
      amounts of Evans blue dye extravasated into the trachea after intravenous
      injections of substance P alone and combined with CGRP. We found that when
      substance P and CGRP were injected together, the amount of plasma extravasation
      produced in the trachea was substantially greater than the amount produced when
      substance P was injected alone. This potentiation was critically dependent on the
      dosage of CGRP and was not observed when relatively high dosages were used. We
      also found that CGRP had a potent hypotensive effect and speculate that reduced
      blood pressure may account for the lack of potentiation observed at the higher
      CGRP dosages. Based on these findings, we conclude that CGRP can potentiate
      substance P-induced plasma extravasation in the rat trachea and may therefore
      play a role in modulating neurogenic inflammation of the airways.

PMID- 1380112
TI  - Detection of proliferating hepatocytes by immunohistochemical staining for
      proliferating cell nuclear antigen (PCNA) in patients with acute hepatic failure.
AB  - This study evaluated whether liver regeneration could take place after massive or
      submassive necrosis of liver cells in 25 patients with several kinds of hepatic
      failure by immunohistochemical staining for proliferating cell nuclear antigen
      (PCNA). PCNA positivity was significantly higher (P less than 0.01) in the
      patients who survived than in the patients who died. Furthermore, PCNA-positive
      hepatocytes were recognized diffusely in the lobule of the liver in survivors.
      There was positive correlation between PCNA positivity and plasma concentration
      of AFP (alpha-fetoprotein), (r = 0.77, P less than 0.01). These results show that
      liver regeneration could take place after massive necrosis of liver cells in
      survivors from acute hepatic failure and that immunohistochemical staining for
      PCNA is useful for prognostic evaluation.

PMID- 1380113
TI  - Phenotypic variation of surface antigenic determinants in Trichomonas vaginalis
      detected by monoclonal antibodies.
AB  - We produced a large panel of murine monoclonal antibodies against surface
      determinants of Trichomonas vaginalis using the hybridoma technique. An
      immunoenzymatic technique (E.L.I.S.A.) was used to screen positive hybrid cells
      producing specific antibodies against the protozoan surface. Eleven monoclonal
      antibodies (Mabs) out of seventy-seven positives were further characterized. We
      tested antibody reactivity in order to investigate the antigenic variance among
      13 different strains of Trichomonas vaginalis of different geographic origin. To
      elucidate the complexity of antigenic expression in Trichomonas vaginalis,
      further characterization of the antigenic pattern in our 13 clinical isolates was
      carried out by immunoblotting techniques. We demonstrate that some monoclonal
      antibodies react with antigens varying in molecular weight in the different
      strains tested. We also demonstrate the pivotal role of protozoan proteases in
      antigenic rearrangement.

PMID- 1380114
TI  - A new bacterial staining method involving Gram stain with theoretical
      considerations of the staining mechanism.
AB  - In order to investigate the mechanism of Gram staining of bacteria, tests with
      anionic dyes followed by treatment with cationic octyltrimethylammonium (OTMA)
      were carried out. The study revealed that tetrabromophenolphthalein ethylester
      (TBPE) gave the most reliable staining of Gram-negative bacteria with negative
      staining of Gram-positive bacteria. Tests on many species of bacteria showed that
      TBPE positive bacteria were Gram-negative and vice versa, without exception.

PMID- 1380115
TI  - Consideration of CASE predictions of genotoxic carcinogenesis for omeprazole,
      methapyrilene and azathioprine.

PMID- 1380116
TI  - Development of a flow-cytometric HLA-A locus mutation assay for human peripheral
      blood lymphocytes.
AB  - A flow-cytometric technique was developed to measure the frequency of variant
      lymphocytes lacking expression of HLA-A2 or A24 allele products among donors
      heterozygous for HLA-A2 or A24. It was found that the variant frequency of
      lymphocytes in peripheral blood was of the order of 10(-4) and increased with
      donor age. Molecular analyses of mutant clones revealed that about one-third were
      derived from somatic recombinations and that the remaining two-thirds did not
      show any alterations after Southern blotting analysis. In contrast, mutants
      obtained after in vitro X-ray mutagenesis study were found to be mostly derived
      from large chromosomal deletions. A small-scale study on atomic bomb survivors
      did not show a significant dose effect.

PMID- 1380117
TI  - Time-saving in biological dosimetry by using the automatic metaphase finder
      Metafer2.
AB  - The amount of time-saving by using the Metafer2 metaphase finder for routine
      analysis of radiation-induced chromosome aberrations (biological dosimetry) was
      determined. Metaphases were prepared by standard methods from cultures of human
      peripheral blood lymphocytes and stained either with Giemsa or with the FPG
      method. The metaphase finder was used for detecting metaphases on the microscope
      slides and for automatically processing the evaluation data. In our laboratory,
      standardized analysis of 1000 metaphases requires at least 3 working days for
      cell culturing and slide preparation and 51.5 working hours for cytogenetic
      analysis. When using the metaphase finder the time required for cytogenetic
      analysis is reduced to 17.3 working hours (time-saving factor: 51.5/17.3 h =
      3.0). In our prolonged method, including more than one scoring of each slide and
      karyotyping of metaphases with chromosome aberrations, the analysis times for
      1000 cells are 132 and 70 working hours, respectively (time saving factor: 132/70
      h = 1.9).

PMID- 1380118
TI  - Assessing overdispersion and dose-response in the male dominant lethal assay.
AB  - In dominant lethal studies the primary variables of interest are typically
      expressed as discrete counts or proportions (e.g., live implants, resorptions,
      percent pregnant). Simple statistical sampling models for discrete data such as
      binomial or Poisson generally do not fit this type of data because of extra
      binomial or extra-Poisson departures from variability predicted under these
      simple models. Extra-variability in the fetal response may originate from
      parental contributions. These can lead to over- or under-dispersion seen as,
      e.g., extra-binomial variability in the proportion response. Utilizing a large
      control database, we investigated the relative impact of extra-variability from
      male or female contributions on the endpoints of interest. Male-related effects
      did not seem to contribute to overdispersion in our database; female-related
      effects were, however, evidenced. Various statistical methods were considered to
      test for significant treatment differences under these forms of sampling
      variability. Computer simulations were used to evaluate these methods and to
      determine which are most appropriate for practical use in the evaluation of
      dominant lethal data. Our results suggest that distribution-free statistical
      methods such as a nonparametric permutation test or rank-based tests for trend
      can be recommended for use.

PMID- 1380119
TI  - Testing by artificial intelligence: computational alternatives to the
      determination of mutagenicity.
AB  - In order to develop methods for evaluating the predictive performance of computer
      driven structure-activity methods (SAR) as well as to determine the limits of
      predictivity, we investigated the behavior of two Salmonella mutagenicity data
      bases: (a) a subset from the Genetox Program and (b) one from the U.S. National
      Toxicology Program (NTP). For molecules common to the two data bases, the
      experimental concordance was 76% when "marginals" were included and 81% when they
      were excluded. Three SAR methods were evaluated: CASE, MULTICASE and CASE/Graph
      Indices (CASE/GI). The programs "learned" the Genetox data base and used it to
      predict NTP molecules that were not present in the Genetox compilation. The
      concordances were 72, 80 and 47% respectively. Obviously, the MULTICASE version
      is superior and approaches the 85% interlaboratory variability observed for the
      Salmonella mutagenicity assays when the latter was carried out under carefully
      controlled conditions.

PMID- 1380120
TI  - Significance testing in mutagen screening: the dependence of statistical power on
      the control sample size.
AB  - The continuous accumulation of control data in multicellular mutagen screening
      systems prompted us to study the dependence of the statistical power on the size
      of the control sample (for fixed control values). Two widely used screening
      systems were chosen: dicentric chromosomes in human lymphocytes and recessive sex
      linked lethals in Drosophila melanogaster. The power increases rapidly at first
      as the control sample size increases, then levels off at a few tens of thousands
      of control units tested and thereafter remains almost constant up to the
      historical control. The practical implications from our study are discussed.

PMID- 1380121
TI  - Comment on the US EPA recommendation for genotoxicity guidelines on chemicals.

PMID- 1380122
TI  - First International Conference on Environmental Mutagens in Human Populations at
      Risk: Cairo, 1992. Summary recommendations that have an impact on genetic
      toxicology research in developing countries.

PMID- 1380123
TI  - Grain counting in the in vitro hepatocyte DNA-repair assay.
AB  - The in vitro hepatocyte DNA-repair assay is a widely used useful method in
      assessing the genotoxic activity of both directly and indirectly acting chemical
      agents. This article discusses the criteria presently employed in the
      autoradiographic evaluation of unscheduled DNA synthesis, and suggests that the
      subtraction of either the average or the highest cytoplasmic grain count, usually
      carried out to obtain the net nuclear grain count, may represent a potential
      source of errors when the test compound is a weakly genotoxic or a non-genotoxic
      agent. As a matter of fact, a response can be classified as positive or negative
      depending on the procedure used to quantitate the cytoplasmic background, and the
      subtraction of this background from the nuclear count is not founded on a sound
      theoretical basis because of the following reasons: the different nature of the
      processes responsible for the generation of nuclear and cytoplasmic grains; and
      the quantitatively different effect that the test compounds may have on the
      nuclear and the cytosolic labelling.

PMID- 1380124
TI  - Further characterization of interactions between gamete surface antigens of
      Plasmodium falciparum.
AB  - Target antigens of malaria transmission blocking immunity include a complex of 3
      gamete surface proteins of 230-kDa and 48/45-kDa glycoproteins. Previous studies
      have shown that epitopes recognized by blocking antibodies are conformational
      (reduction sensitive) in nature. Studies were conducted to characterize the
      interactions between the target antigens and role of disulfide groups in the
      formation of the complex. Treatment of detergent extracts of gametes with
      chaotropic agents and extremes of pH resulted in dissociation of the complex. The
      interaction between the 3 proteins was also perturbed when the extract was
      incubated in the presence of antibodies against the 230-kDa protein but not
      against the 48/45-kDa doublet. Chemical modifications of disulfide and sulfhydryl
      groups in the target antigens, otherwise inaccessible either in the total extract
      or after phase separation in Triton X-114, required prior denaturation of
      antigens.

PMID- 1380125
TI  - Surface epitope variation via mosaic gene formation is potential key to long-term
      survival of Trypanosoma brucei.
AB  - Trypanosoma brucei evades the immune response of its mammalian host by antigenic
      variation in the major surface antigen (the variable surface glycoprotein or
      VSG). We examined the generation of diversity in 4 in vivo-derived antigenically
      related clones of T. brucei by sequencing VSG cDNA from each of the 4 clones and
      all 5 related genomic copies in the WaTat 1.1 progenitor organism. Each expressed
      VSG gene was a different mosaic of basic copy genes; 3 were complex mosaics
      consisting of multiple fragments from at least 3 basic copy genes. All 4 basic
      copy genes were involved in mosaic gene formation even though at least 2 were
      pseudogenes. Point mutations were a minor component to VSG variability. We
      conclude that, in vivo, expression of mosaic VSG genes amplifies the effective
      surface antigen repertoire of T brucei. We propose that this additional source of
      antigenic variation is crucial to long term survival of the parasite in its
      mammalian host, and may be the primary function of VSG multigene families in
      trypanosomes.

PMID- 1380126
TI  - Comparative serological reactivity of Taenia crassiceps, Taenia solium and Taenia
      saginata metacestode neutral glycolipids to infection serum from Taenia
      crassiceps-infected mice.
AB  - A comparative survey was undertaken of the neutral fraction glycolipids from the
      metacestodes of 3 taeniid species, Taenia crassiceps, Taenia solium and Taenia
      saginata, to determine their chemical and serological staining patterns on
      separation by thin-layer chromatography. The orcinol-positive patterns of T.
      solium and T. saginata metacestodes exhibited a closer superficial resemblance to
      each other than to T. crassiceps or T. saginata adults. A comparison of component
      migration properties against standards of known structure indicated the main
      oligosaccharide chains to be mono-, di-, tri- and tetrasaccharides; however, in
      T. solium this was extended to at least a heptasaccharide. The multiple banding
      characteristic of each component is a consequence of lipid moiety heterogeneity.
      Serologically, the patterns of the 3 taeniid species neutral fraction glycolipids
      showed virtually the same immunological reactivity towards mouse normal serum,
      infection serum and a monospecific, polyclonal antibody directed against the
      trisaccharide component of T. crassiceps. The latter antibody was isolated from
      mouse infection serum by affinity chromatography on a column of glycolipid-bound
      octyl-Sepharose CL-4B. Immunochemically, the major common epitope expressed by
      the neutral fraction glycolipids of the 3 taeniid species is the same or very
      similar to the glycosphingolipid, neogalatriaosyl ceramide derived from the
      marine mollusc Turbo cornutus (Gal(beta 1-6) Gal(beta 1-6) Gal(beta 1-1)Cer).
      Host tissue neutral fraction glycolipids, porcine muscle and bovine muscle, as
      well as human spleen, were not immunoreactive.

PMID- 1380127
TI  - Cystic fibrosis. Chloride channels revisited.

PMID- 1380128
TI  - RNA catalysis. Evolution on fast-forward.

PMID- 1380129
TI  - Defective regulation of outwardly rectifying Cl- channels by protein kinase A
      corrected by insertion of CFTR.
AB  - Cystic fibrosis (CF) is a lethal genetic disease resulting in a reduced Cl-
      permeability, increased mucous sulphation, increased Na+ absorption and defective
      acidification of lysosomal vesicles. The CF gene encodes a protein (the cystic
      fibrosis transmembrane conductance regulator, CFTR) that can function as a low
      conductance Cl- channel with a linear current-voltage relationship whose
      regulation is defective in CF patients. Larger conductance, outwardly rectifying
      Cl- channels are also defective in CF and fail to activate when exposed either to
      cyclic AMP-dependent protein kinase A or to protein kinase C. The role of the
      outwardly rectifying Cl- channel in CF has been questioned. We report here that
      expression of recombinant CF genes using adeno-associated virus vectors in CF
      bronchial epithelial cells corrects defective Cl- secretion, that it induces the
      appearance of small, linear conductance Cl- channels, and restores protein kinase
      A activation of outwardly rectifying Cl- channels. These results re-establish an
      involvement of outwardly rectifying Cl- channels in CF and suggest that CFTR
      regulates more than one conductance pathway in airway tissues.

PMID- 1380130
TI  - High brain densities of the immunophilin FKBP colocalized with calcineurin.
AB  - The immunophilins cyclophilin and FK506 binding protein (FKBP) are small,
      predominantly soluble proteins that bind the immunosuppressant drugs cyclosporin
      A and FK506, respectively, with high affinity, and which seem to mediate their
      pharmacological actions. The Ca(2+)-dependent protein phosphatase, calcineurin,
      binds the cyclophilin-cyclosporin A and FKBP-FK506 complexes, indicating that
      calcineurin might mediate the actions of these drugs. A physiological role for
      the immunophilins in the nervous system is implied by a close homology between
      the structure of NINA A, a protein in the neural retina of Drosophila, and
      cyclophilin, as well as by the high density of FKBP messenger RNA in brain
      tissue. Here we report that the levels of FKBP and mRNA in rat brain are
      extraordinarily high and that their regional localization is virtually identical
      to that of calcineurin, indicating that there may be a physiological link between
      calcineurin and the immunophilins. We also show that at low concentrations FK506
      and cyclosporin A enhance the phosphorylation of endogenous protein substrates in
      brain tissue and in intact PC12 cells, indicating that these drugs may inhibit
      phosphatase activity by interacting with the immunophilin-calcineurin complexes.

PMID- 1380131
TI  - Viral hepatitis: modern aspects of clinical diagnosis.
AB  - In these years, more light has been brought into the field of hepatitis viruses,
      particularly with regard to their biology and etiopathogenesis. Besides, first
      attempts of specific therapy have been done, thanks to the introduction of
      interferons. This paper wants to give the main guidelines of up-to-date diagnosis
      and treatment of hepatitis supported by viral infection.

PMID- 1380132
TI  - Comparison of anti-hepatitis C virus detection with ELISA assay and RIBA 4 in
      dialysis patients: our experience.
AB  - Hepatitis C virus (HCV) has been demonstrated to be the main cause of non-A, non
      B hepatitis and the emergent infectious illness in dialysis units. At present,
      the anti-HCV 100 ELISA and an immunoblot assay in which 2 new antigens are
      included, are available. We have tested 110 patients on chronic dialysis with
      anti-C100 ELISA. Twenty-seven of them were anti-HCV positive. We tested the 27
      anti-HCV-positive and 7 anti-HCV-negative patients with the RIBA 4 assay. The
      results were similar with both test.

PMID- 1380133
TI  - Hepatitis C virus infection in hemodialyzed patients detected by first and second
      generation assays.
AB  - A prospective study of liver disease has been conducted among patients entering
      our Dialysis Unit between 1987 and 1990. On entry, 7 patients had a history of
      blood transfusions but none had clinical or biochemical features of liver
      disease. During follow-up, 13 further patients were transfused; 1 case developed
      acute resolving hepatitis B and another acute non-A, non-B hepatitis progressing
      to chronicity. Eleven other cases showed transient or fluctuating ALT
      abnormalities. On entry, anti-HCV was negative by both 1st and 2nd generation
      ELISA assays (Ortho-Diagnostic Systems) in all cases. During follow-up, a
      positive reaction was detected in 17 cases: 4 patients were positive by both
      assays and 13 only by 2nd generation test (p less than 0.01). HCV was implicated
      in 66% of cases with liver disease of the non-A, non-B type and in 50% of
      transfused as compared to 23% of nontransfused cases (p = n.s.). These findings
      suggest that HCV could play a major etiological role in liver disease of
      hemodialysis patients and that anti-C100 reactivity is more affected by
      immunosuppression associated with chronic uremia.

PMID- 1380134
TI  - Deficit of galanin-like immunostaining in the median eminence of adult
      hypothyroid rats.
AB  - In this paper we describe the modification of the galanin (GAL)-like
      immunostaining in the hypothalamus of rats, which were made hypothyroid at 52
      days after birth. On 21st day after the surgical ablation of the thyroid gland,
      the staining of the GAL-immunoreactive fibers in the median eminence decreased
      and on the 84th day disappeared almost totally. The GAL-immunoreactive
      distribution in other areas of the hypothalamus, e.g. the anterior hypothalamus
      and the dorsomedial nucleus, is only slightly affected by the absence of thyroid
      hormones, whereas the GAL-staining of medulla oblongata (vagal complex) is equal
      in both control and hypothyroid rats. In hypothyroid colchicine-treated rats, we
      were unable to stain GAL-immunoreactive neurons in the paraventricular nucleus
      (PVN). Oxytocin- and vasopressin-like material was present in the magnocellular
      neurons and the staining pattern in hypothyroid rats was the same as that of
      control animals. Our data show a marked reduction in the expression of the GAL
      like immunoreactivity of the PVN and median eminence of adult hypothyroid rats.
      The possible role of this deficit in the pathogenesis of the GH secretion
      impairment that is observed in hypothyroid rats is discussed.

PMID- 1380135
TI  - Distribution and cerebellar projections of cholinergic and corticotropin
      releasing factor-containing neurons in the caudal vestibular nuclear complex and
      adjacent brainstem structures.
AB  - By using immunohistochemistry combined with lesioning and retrograde neuronal
      labeling techniques, cholinergic neurons and corticotropin-releasing factor
      immunoreactive neurons were examined for their distribution, coincidence and
      cerebellar projections in feline vestibular nuclear complex and adjacent
      brainstem structures. Cholinergic neurons as revealed here with choline
      acetyltransferase immunoreactivity were found massively in the abducens and
      hypoglossal nuclei, dorsal motor nucleus of the vagus nerve and nucleus of
      Roller; less numerously in the medial vestibular, prepositus hypoglossi and
      solitary nuclei and the caudal two-thirds of descending vestibular nucleus; and
      only occasionally in the intercalated and supravestibular nuclei and cell groups
      f, x and z. Corticotropin-releasing factor-immunoreactive neurons were found
      clustered in the prepositus hypoglossi nucleus and also in cell groups f and x
      and the rostral two-thirds of descending vestibular nucleus, less numerously in
      the medial vestibular, intercalated and solitary nuclei and nucleus of Roller,
      and only occasionally in the caudal one-third of descending vestibular nucleus,
      the dorsal motor nucleus of the vagus nerve, supravestibular nucleus and cell
      group z. The lateral and superior vestibular nuclei did not contain either type
      of neuron. The two types of immunopositive neurons observed in most of the
      brainstem nuclei differed in cell size, distribution-pattern and rostrocaudal
      level of occurrence. While there were many regions which exhibited both types of
      immunopositive neurons, perikarya colocalizing the cholinergic and peptide
      markers were not detected in the brainstem. Following unilateral, partial
      lesioning of the vestibular nuclear complex, corticotropin-releasing factor
      immunoreactive mossy fiber terminals (rosettes) disappeared from the ipsilateral
      flocculus. However, such lesions did not produce clear-cut changes of cholinergic
      terminals in the vermis. Following retrograde neuronal labeling combined with
      immunohistochemistry, the two types of immunopositive neurons observed in most of
      the brainstem sites were found to project to the vermal lobules I-III, IX and X.
      On comparison of these immunopositive projection neurons with non-immunoreactive,
      retrogradely labeled neurons, the cholinergic neurons and the peptide
      immunoreactive neurons were found to constitute a major part of the total
      vestibulocerebellar neuronal population. The results indicate chemical
      heterogeneity in vestibular nuclear complex and cerebellar afferents.

PMID- 1380136
TI  - Collateralized projections from neurons in the rostral medulla to the nucleus
      locus coeruleus, the nucleus of the solitary tract and the periaqueductal gray.
AB  - We have examined collateral projections of locus coeruleus afferent neurons in
      the rostral medulla to the caudal nucleus of the solitary tract or to the
      periaqueductal gray using double retrograde labeling techniques in the rat. The
      present findings confirm previously reported connections to the locus coeruleus,
      the nucleus of the solitary tract and the lateral periaqueductal gray from the
      nucleus paragigantocellularis in the rostral ventral medulla. Our results also
      reveal previously unreported projections from the rostral dorsomedial medulla (in
      a similar region as locus coeruleus-projecting neurons) to the lateral
      periaqueductal gray. Following retrograde tracer injections into the nucleus of
      the solitary tract and the locus coeruleus, doubly labeled neurons were seen in
      both the nucleus paragigantocellularis and in the rostral dorsomedial medulla.
      Cell counts revealed that approximately 25% of locus coeruleus-projecting neurons
      in the nucleus paragigantocellularis, and 12% in the dorsomedial medulla, also
      innervate the caudal nucleus of the solitary tract. In contrast, no doubly
      labeled neurons within the rostral ventral medulla were found following
      injections into the lateral periaqueductal gray and the locus coeruleus, although
      singly labeled neurons for the two tracers were interdigitated in some regions.
      Following these injections, numerous neurons were also retrogradely labeled in
      the dorsomedial medulla in the region of the medial prepositus hypoglossi and the
      perifascicular reticular formation. A small percentage of locus coeruleus
      afferents in the dorsal medulla (approximately 10%) also projected to the lateral
      periaqueductal gray. These results indicate that neurons in both the
      ventrolateral and dorsomedial rostral medulla frequently send collaterals to both
      the locus coeruleus and the caudal nucleus of the solitary tract. A small number
      of neurons in the dorsomedial medulla project to both the locus coeruleus and the
      lateral periaqueductal gray, but separate populations of neurons project to the
      locus coeruleus and the lateral periaqueductal gray from the ventrolateral
      medulla. These results functionally link the locus coeruleus and the nucleus of
      the solitary tract by virtue of common afferents, and support other studies
      indicating the importance of central autonomic circuitry in the afferent control
      of locus coeruleus neurons.

PMID- 1380137
TI  - Antinociception induced by microinjection of substance P into the A7
      catecholamine cell group in the rat.
AB  - Stimulation of neurons in the ventromedial medulla produces antinociception that
      is mediated in part by indirect activation of pontospinal noradrenergic neurons.
      Substance P-containing neurons located in the ventromedial medulla project to the
      A7 catecholamine cell group and may serve as an excitatory link between these two
      cell groups. Thus, the antinociception induced by stimulation of the neurons in
      ventromedial medulla may be mediated by substance P released from these
      projections which activates spinally projecting noradrenergic neurons in the A7
      cell group. This hypothesis was tested by determining whether microinjection of
      various doses of substance P into the A7 cell group of the rat could induce
      antinociception. The results indicated that substance P induced dose-dependent
      antinociception that was more pronounced in the hindlimb ipsilateral to the
      microinjections. This observation is consistent with anatomical observations that
      noradrenergic A7 neurons project predominantly to the ipsilateral spinal cord
      dorsal horn. Moreover, the antinociceptive effects of substance P microinjection
      appear to be mediated at least in part by activation of spinally projecting
      noradrenergic neurons in the A7 cell group, because intrathecal injections of the
      alpha-2 noradrenergic antagonists yohimbine and idazoxan blocked these
      antinociceptive effects. The results of these experiments support the hypothesis
      that the antinociception induced by stimulation of neurons in the ventromedial
      medulla is mediated in part by activation of substance P-containing neurons that
      project to, and activate, spinally projecting noradrenergic neurons located in
      the A7 catecholamine cell group.

PMID- 1380138
TI  - Increased content and transport of substance P and calcitonin gene-related
      peptide in sensory nerves innervating inflamed tissue: evidence for a regulatory
      function of nerve growth factor in vivo.
AB  - The responses of sensory neuropeptides during unilateral, Freund's adjuvant
      induced, paw inflammation in the rat were examined. After five days of
      inflammation, the substance P and calcitonin gene-related peptide content in the
      sciatic nerve supplying the inflamed paw were increased by 60-75% when compared
      with the contralateral side. At this time-point, there was also a 30-40% increase
      in the substance P and calcitonin gene-related peptide content of the dorsal root
      ganglia (L4-L6), and a 40% increase in the calcitonin gene-related peptide
      content of the L4-L6 segments of the dorsal spinal cord on the inflammation side.
      In the dorsal root ganglia, calcitonin gene-related peptide content was also
      increased as early as 12 h and 48 h after induction of paw inflammation. On day 5
      of inflammation, the axonal transport of both sensory neuropeptides towards the
      inflamed paw, as determined after sciatic nerve ligation, was also markedly
      increased as compared with the control side. Despite this increased transport,
      the amount of substance P and calcitonin gene-related peptide present in the
      inflamed paw itself was either reduced or remained unchanged from day 1 through
      to day 5 of inflammation pointing towards reduced storage and increased release
      of the peptides in the inflamed tissue. Nerve growth factor content was markedly
      increased in the sciatic nerve of the inflamed paw with a peak of +136% at time
      point 24 h after induction of inflammation. When rats were systemically treated
      with anti-nerve growth factor serum, the increase in neuropeptide content in the
      sciatic nerve of the inflamed paw (day 5) was prevented. On the other hand, local
      injections of nerve growth factor for 5 days into a noninflamed paw were able to
      induce an increase in substance P and calcitonin gene-related peptide content in
      the supplying sciatic nerve. These findings point towards a regulatory function
      for nerve growth factor in vivo in the stimulation of sensory neuropeptide
      synthesis during prolonged inflammatory processes.

PMID- 1380139
TI  - Substance P and calcitonin gene-related peptide in the ureter of chicken and
      guinea-pig: distribution, binding sites and possible functions.
AB  - To elucidate the possible functional significance of sensory neuropeptides in
      visceral organs of mammals and birds the distribution, binding sites and the
      effects on ureteric peristalsis of substance P and calcitonin gene-related
      peptide (CGRP) were investigated in the ureter of guinea-pigs and chickens. In
      the guinea-pig numerous substance P and CGRP-immunoreactive fibres were located
      in the adventitia, smooth muscle layer, submucosa and occasionally in the
      epithelium. Varicose peptidergic fibres were often found on blood vessels.
      Binding sites for substance P were associated with blood vessels and epithelium
      in the following density order: venules greater than epithelium greater than
      arterioles. The highest density of CGRP binding sites was detected on the smooth
      muscle; venules and arterioles expressed moderate binding. The peristalsis
      frequency of the isolated ureter of the guinea-pig was increased by neurokinin A
      and substance P, whereas CGRP inhibited ureteric motility. In the chicken the
      immunoreactivity to substance P and CGRP was less pronounced. Immunoreactive
      fibres were found in the submucosa close to the epithelium and around ureteric
      ganglion cells. Correspondingly, substance P binding sites were located in the
      epithelium and in ureteric ganglia; however, specific CGRP binding was restricted
      to large blood vessels. In the chicken none of the sensory neuropeptides affected
      ureteric motility. Only high doses of the sensory neurotoxin capsaicin (greater
      than 10 microM) repeatedly produced a non-specific inhibitory effect, similar to
      that found in a capsaicin-desensitized guinea-pig ureter preparation. The data
      suggest that in the guinea-pig ureter sensory neuropeptides play a modulatory
      role in the regulation of ureteric motility and might have vascular and
      epithelial functions. In the chicken, substance P might be involved in the
      regulation of epithelial function and modulation of ganglionic transmission. The
      physiological or pathophysiological role of sensory neuropeptides and the
      efferent functions of afferent fibres appears to be much better developed in the
      guinea-pig than in the chicken.

PMID- 1380140
TI  - The sensory and sympathetic innervation of guinea-pig lung and trachea as studied
      by retrograde neuronal tracing and double-labelling immunohistochemistry.
AB  - The sympathetic and sensory innervation of guinea-pig trachea and lung were
      studied by means of retrograde neuronal tracing using fluorescent dyes, and
      double-labelling immunofluorescence. Sympathetic neurons supplying the lung were
      located in stellate ganglia and in thoracic sympathetic chain ganglia T2-T4;
      those supplying the trachea resided in the superior cervical and stellate
      ganglia. Retrogradely labelled sympathetic neurons were usually immunoreactive to
      tyrosine hydroxylase; the majority also contained neuropeptide Y
      immunoreactivity. However, a small number were non-catecholaminergic (i.e.
      tyrosine hydroxylase negative), but neuropeptide Y immunoreactive. Within the
      airways, tyrosine hydroxylase/neuropeptide Y-immunoreactive axons were found in
      the smooth muscle layer, around blood vessels including the pulmonary artery and
      vein, and to a lesser extent in the lamina propria. Periarterial axons contained
      in addition dynorphin immunoreactivity. Sensory neurons supplying the lung were
      located in jugular and nodose vagal ganglia as well as in upper thoracic dorsal
      root ganglia; those supplying the trachea were most frequently found bilaterally
      in the nodose ganglia and less frequently in the jugular ganglia. A spinal origin
      of tracheal sensory fibres could not be consistently demonstrated. With regard to
      their immunoreactivity to peptides, three types of sensory neurons projecting to
      the airways could be distinguished: (i) substance P/dynorphin immunoreactive;
      (ii) substance P immunoreactive but dynorphin negative; and (iii) negative to all
      peptides tested. Substance P-immunoreactive neurons innervating the airways
      invariably contained immunoreactivity to neurokinin A and calcitonin gene-related
      peptide. Retrogradely labelled neurons located in the nodose ganglia belonged
      almost exclusively (greater than or equal to 99%) to the peptide-negative group,
      whereas the three neuron types each represented about one-third of retrogradely
      labelled neurons in jugular and dorsal root ganglia. Within the airways, axons
      immunoreactive to substance P/neurokinin A and substance P/calcitonin gene
      related peptide were distributed within the respiratory epithelium of trachea and
      large bronchi, in the lamina propria and smooth muscle from the trachea down to
      the smallest bronchioli (highest density at the bronchial level), in the alveolar
      walls, around systemic and pulmonary blood vessels, and within airway ganglia.
      Those axons also containing dynorphin immunoreactivity were restricted to the
      lamina propria and smooth muscle. The origin of nerve fibres immunoreactive for
      vasoactive intestinal polypeptide, of which a part were also neuropeptide Y
      immunoreactive, could not be determined by retrograde tracing experiments.
      Vasoactive intestinal polypeptide-immunoreactive fibres terminating within airway
      ganglia may be of preganglionic parasympathetic origin, whereas others (e.g.
      those found in smooth muscle) may arise from intrinsic ganglia.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1380141
TI  - Acute phase proteins but not activated microglial cells are present in
      parenchymal beta/A4 deposits in the brains of patients with hereditary cerebral
      hemorrhage with amyloidosis-Dutch type.
AB  - With immunohistochemical staining methods on cryostat sections we investigated
      the brains of three patients with hereditary cerebral hemorrhage with amyloidosis
      Dutch type, one of the cerebral beta/A4 amyloid diseases. Immunostaining for
      beta/A4 protein revealed numerous non-fibrillar beta/A4 depositions (amorphous or
      diffuse plaques) in the brain parenchyma in addition to extensive vascular
      amyloid deposition. All amorphous plaques contain complement proteins and alpha 1
      antichymotrypsin but activated microglial cells expressing major
      histocompatibility (MHC) class II antigens HLA-DR and leucocyte adhesion
      molecules belonging to the lymphocyte-function-associated antigen (LFA)-1 family
      are virtually absent in cortical gray matter. Our findings are discussed from the
      view that a cascade of events including acute phase proteins and activated
      microglial cells are involved in classical amyloid plaque formation.

PMID- 1380142
TI  - Purification and characterization of fibroblast growth factors from the opossum,
      Monodelphis domestica, brain.
AB  - An extract from the brain of the opossum Monodelphis domestica was fractionated
      by heparin affinity chromatography. A major peak of mitogenic activity (heparin
      binding growth factor 2, HBGF-2) eluted from heparin-Sepharose between 1.7 and
      2.0 M NaCl. Antisera specific for bovine bFGF detected four polypeptides of 17.5
      23 kDa in opossum brain HBGF-2 preparations. Opossum brain heparin binding growth
      factor 1 (HBGF-1), a minor peak of activity, eluted from heparin-Sepharose at 1.1
      NaCl and contained a 16.2 kDa protein that cross-reacted with antiserum against
      bovine aFGF.

PMID- 1380143
TI  - Recovery from the rapid desensitization of nicotinic acetylcholine receptor
      channels on mouse muscle.
AB  - Pulses of acetylcholine (ACh) applied to outside-out patches of embryonic-like
      muscle membrane elicited channel currents which declined rapidly (tau d = 10-60
      ms) due to desensitization. Recovery from desensitization was determined by pulse
      pairs, varying the pulse interval. When the pulse interval was about 300 ms, the
      response to the second pulse was about half that to the first pulse, i.e. about
      half of the channels had recovered from desensitization. The results are
      discussed in the frame of a cyclic reaction scheme. If this scheme includes high
      affinity binding of ACh to desensitized receptors, it can also explain the
      finding that low ACh concentrations (less than or equal to 1 microM) largely
      desensitize the receptors, but elicit very little channel opening.

PMID- 1380144
TI  - The proportion of galanin-immunoreactive neurons in mouse trigeminal ganglia is
      transiently increased following corneal inoculation of herpes simplex virus type
      1.
AB  - To investigate whether neurobiological functions are modified by viral infection,
      we inoculated mouse corneas with herpes simplex virus type 1 (HSV-1) and examined
      neuronal galanin content in trigeminal ganglia at selected survival times. HSV-1
      antigen appeared in neurons at day 3, peaked at day 6 and disappeared by day 11.
      Increased galanin positivity was first seen at day 6, peaked at day 10 and
      approached control values by day 21. This result provides further evidence that
      the biological program of peripheral sensory neurons is modified by herpes-virus
      infection.

PMID- 1380145
TI  - Nerve growth factor regulation of choline acetyltransferase gene expression in
      rat embryo basal forebrain cultures.
AB  - Nerve growth factor (NGF) increases the activity of choline acetyltransferase
      (ChAT), the synthetic enzyme for acetylcholine, in rat basal forebrain neurons
      both in vivo and in vitro. In poly(A)+ RNA isolated from cultures prepared from
      the embryonic (E15) rat basal forebrain, radiolabeled probes from the human ChAT
      gene detected a 3,700 nt and a less abundant 2,300 nt transcript. After growth in
      the presence of NGF, the abundance of both mRNAs was increased approximately
      twofold, paralleling the increase in ChAT enzyme activity. In vivo, the human
      ChAT probes detected a single 3,700 nt form of ChAT mRNA in both embryonic and
      adult rat basal forebrain. These results suggest that the NGF-mediated increase
      in ChAT activity in basal forebrain cultures is regulated at the transcriptional
      level.

PMID- 1380146
TI  - Acidic amino acids evoke a smaller [Ca2+]i rise in GABAergic than non-GABAergic
      hippocampal neurons.
AB  - Changes in intracellular calcium concentration ([Ca2+]i) in response to topical
      application of the glutamate agonists N-methyl-D-aspartate (NMDA), or amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were measured in cultured rat
      hippocampal neurons loaded with Fluo-3 and visualized in a confocal laser
      scanning microscope. These neurons were subsequently stained for the presence of
      the enzyme marker for gamma-amino butyric acid (GABA), glutamate decarboxylase
      (GAD). GAD-positive, putative interneurons were less responsive to NMDA and AMPA
      than GAD-negative neurons. The time course of the rise and decay of [Ca2+]i was
      similar in the two groups of neurons. Also, there was no clear difference in the
      shape and size of these two neuron groups indicating that the difference between
      them is not due to diffusion distances. These data indicate that interneurons are
      probably more able to handle a calcium load than other neurons, a difference that
      may underly their resistance to treatments which cause degeneration of other
      neurons in the hippocampus.

PMID- 1380147
TI  - Intracellular injection of vital dyes into single cells in the salamander
      olfactory epithelium.
AB  - Intracellular vital dye injection was used to examine the morphology of single
      sustentacular and receptor cells and the developmental fate of individual basal
      cells in the olfactory epithelium of the tiger salamander. In acute experiments,
      Lucifer yellow injections were used to identify single basal, receptor or
      sustentacular cells on the basis of their overall morphology. Dye-coupling
      between a number of the different epithelial cells was observed. Progeny of basal
      cells were examined by following labeled cells for up to 2 weeks using
      intracellular injection of rhodamine-labeled dextran. These experiments indicate
      that some olfactory epithelial cells are dye-coupled and that dye-filled basal
      cells can undergo division and migration.

PMID- 1380148
TI  - CODE chemotherapy with or without recombinant human granulocyte colony
      stimulating factor in extensive-stage small cell lung cancer.
AB  - CODE therapy demonstrated high antitumor activity in extensive-stage small cell
      lung cancer (SCLC). Toxicity was acceptable in a regimen with a nine-cycle
      schedule. The results obtained in this study suggest that CODE therapy improves
      the outcome of patients with extensive-stage SCLC. The use of recombinant human
      granulocyte colony-stimulating factor may well reduce the duration and degree of
      neutropenia during CODE chemotherapy and increase the dose intensity, leading to
      further improvement of outcome.

PMID- 1380149
TI  - Reversion of middle T antigen-transformed Rat-2 cells by Krev-1: implications for
      the role of p21c-ras in polyomavirus-mediated transformation.
AB  - Polyomavirus middle T antigen mediates transformation of cells, at least in part,
      by its association with and activation of the intrinsic protein tyrosine kinase
      activity of pp60c-src. pp60c-src, by analogy with pp60v-src, elicits cell
      proliferation through a signal transduction pathway that includes p21c-ras.
      Therefore, we tested the possibility that middle T antigen acts upstream of and
      in the same proliferative signaling pathway as p21c-ras. Co-transfection of Rat-2
      cells with plasmids expressing human Krev-1, a dominant suppressor of Ki-ras
      transformation, and mT antigen resulted in a dose-dependent reduction of mT
      antigen-induced foci. Krev-1 did not affect the transforming activity of SV40
      large T antigen, demonstrating that the transformation-suppressing activity of
      Krev-1 is specific. To determine the effect of Krev-1 on stably transformed cell
      lines, Krev-1 DNA was introduced into middle T antigen-transformed Rat-2 cells
      along with a G418 resistance marker. Of the G418-resistant colonies examined, 1%
      were morphologically untransformed. Characterization of several morphological
      revertants revealed that, with the exception of one cell line, all of the cell
      lines expressed middle T antigen, which was associated with pp60c-src, whose
      tyrosine kinase activity was similar to that found in the parental transformed
      cell lines. To determine whether other phenotypic traits associated with
      transformation were altered in these cell lines, their growth rates and ability
      to form colonies in agar suspension were examined. The majority of the revertants
      had longer doubling times, and grew less efficiently in agar suspension compared
      with their transformed parents. A direct correlation was observed between Krev-1
      RNA and protein expression and the efficiency with which the revertants formed
      colonies in suspension. These results suggest that p21c-ras lies downstream of
      middle T antigen and pp60c-src in the same proliferative signal transduction
      pathway.

PMID- 1380150
TI  - Retinoic acid receptor alpha suppresses polyomavirus transformation and c-fos
      expression in rat fibroblasts.
AB  - To explore the molecular mechanisms by which retinoic acid inhibits oncogenic
      transformation, we have examined the effects of retinoic acid on the polyomavirus
      induced transformation of rat fibroblasts. Treatment of rat F111 fibroblasts with
      high concentrations of retinoic acid (10(-6) M) partially inhibited the ability
      of polyomavirus to induce dense focus formation (50-70%). This effect was not
      secondary to a retinoic acid-dependent block of cellular proliferation. To
      address the role of the retinoic acid receptor (RAR-alpha) in mediating the
      transformation-inhibitory effect of retinoic acid, we have overexpressed either
      RAR-alpha or cellular retinoic acid-binding protein I (CRABP) cDNAs in F111
      cells. Introduction of a CRABP I expression vector did not alter the
      responsiveness of F111 cells to retinoic acid in any detectable fashion. In
      contrast, overexpression of RAR-alpha increased the sensitivity of F111 cells to
      the transformation-inhibitory action of retinoic acid by 10- to 100-fold. At high
      concentrations, retinoic acid inhibited transformation of F111-RAR cells by
      polyomavirus by about 90%. At near physiological concentrations, retinoic acid
      inhibited transformation by 25-50% in F111-RAR cells but not in control cells.
      Retinoic acid did not inhibit either the synthesis of polyoma middle T (mT) or
      pp60c-src, the cellular target for mT action, or the formation of mT:pp60c-src:PI
      3 kinase (phosphatidylinositol-3 kinase) complexes. Therefore, RAR-alpha was not
      acting as a negative regulator of expression of either the polyomavirus middle T
      oncogene or the cellular proto-oncogene, c-src. It seems likely that RAR-alpha
      regulates the expression of cellular genes whose products interact in some way
      with mT-regulated signaling pathways, leading to a ligand-dependent suppression
      of polyoma transformation. In addition, RAR-alpha overexpression selectively
      inhibits the serum-stimulated expression of the c-fos gene, but does not affect
      the expression of a number of other serum- and polyomavirus-inducible genes
      including c-jun, junB, c-myc and actin.

PMID- 1380151
TI  - A requiem for aniline dyes.

PMID- 1380152
TI  - Ion conductances in the microvillous and basal membrane vesicles isolated from
      human placental syncytiotrophoblast.
AB  - Experiments were performed to characterize the ionic conductances in microvillous
      and basal membranes from human placenta. Microvillous and basal membranes were
      prepared from term placental tissue by homogenization, magnesium precipitation,
      differential and sucrose density gradient centrifugation. The relative
      permeabilities of sodium, potassium and chloride were measured using the bi-ionic
      potential technique which employs a fluorescent probe [diS-C3-(5)] which
      partitions into membranes in a potential-dependent manner. The permeabilities of
      sodium and chloride relative to potassium were determined by measuring their
      effects on a known membrane potential produced by a potassium gradient. In
      microvillous membranes PNa/PK = 0.25 and PClPK = 0.19 while in basal membranes,
      PNa/PK = 1.31 and PCl/PK = 0.03. Measurements of chloride permeability relative
      to sodium confirmed these results. The cation conductances were inhibited by
      quaternary ammonium compounds. Addition of tetramethylammonium altered the
      relative permeabilities in a pattern suggesting a block of potassium conductance
      while tetraethylammonium appeared to block both sodium and potassium
      conductances.

PMID- 1380153
TI  - Hepatocyte nuclear factor 1 alpha is expressed in a hamster insulinoma line and
      transactivates the rat insulin I gene.
AB  - Systematic mutational analysis previously identified two primary regulatory
      elements within a minienhancer (-247 to -198) of the rat insulin I promoter that
      are critical for transcriptional activity. The Far box (-241 to -232) and the
      FLAT element (-222 to -208) synergistically upregulate transcription and,
      together, are sufficient to confer tissue-specific and glucose-responsive
      transcriptional activity on a heterologous promoter. Detailed analysis of the
      FLAT element further revealed that, in addition to the positive regulatory
      activity it mediates in tandem with the Far box, it is a site for negative
      regulatory control. A portion of the FLAT element bears considerable sequence
      similarity to the consensus binding site for hepatocyte nuclear factor 1 alpha
      (HNF1 alpha; LF-B1) a liver-enriched homeodomain-containing transcription factor.
      Here we show that the HNF1-like site within the FLAT element exhibited positive
      transcriptional activity in both HepG2 and HIT cells and bound similar, but
      distinguishable, nuclear protein complexes in the respective nuclear extracts.
      Screening of a hamster insulinoma cDNA library with a PCR-derived probe
      encompassing the DNA-binding domain of rat HNF1 alpha resulted in isolation of a
      hamster HNF1 alpha (hHNF1 alpha) cDNA homolog. Specific antiserum identified the
      HNF1 alpha protein as one component of a specific FLAT-binding complex in HIT
      nuclear extracts. Expression of the hHNF1 alpha cDNA in COS cells resulted in
      transactivation of reporter constructs containing multimerized segments of the
      rat insulin I minienhancer. Thus, HNF1 alpha, one component of a DNA-binding
      complex involved in transcriptional regulation of the rat insulin I gene, may
      play a significant role in nonhepatic as well as hepatic gene transcription.

PMID- 1380154
TI  - Specificity of antisense oligonucleotides in vivo.
AB  - Antisense oligonucleotides are widely used as inhibitors of gene expression in
      cultured cells and have been proposed as potential therapeutic agents, but it is
      not known to what extent they are specific for their intended target RNAs.
      Statistical considerations indicate that if oligonucleotides can form hybrids
      with mRNA molecules in vivo by means of short or imperfect regions of
      complementarity, then the specificity of oligonucleotides as antisense reagents
      will be greatly compromised. We have used Xenopus oocytes as a model system in
      which to investigate the potential specificity of antisense oligonucleotides in
      vivo. We injected perfect and partially matched antisense oligonucleotides into
      oocytes and measured the resulting degradation of the target RNA in each case. On
      the basis of the extent to which antisense oligonucleotides can cause cleavage of
      RNAs at imperfectly matched target sites, we conclude that in this system it is
      probably not possible to obtain specific cleavage of an intended target RNA
      without also causing at least the partial destruction of many nontargeted RNAs.

PMID- 1380155
TI  - Support of human hematopoiesis in long-term bone marrow cultures by murine
      stromal cells selectively expressing the membrane-bound and secreted forms of the
      human homolog of the steel gene product, stem cell factor.
AB  - The maintenance and differentiation of hematopoietic stem cells is influenced by
      cells making up the hematopoietic microenvironment (HM), including bone marrow
      derived stromal cells. We and several other investigators have recently
      demonstrated the molecular basis of abnormal HM observed in the steel mutant
      mouse and cloned the normal cDNA products of this gene (termed SCF, KL, or MCF).
      In this report, we focus on the human counterpart of the mouse Steel (Sl) gene.
      Alternative splicing of the human SCF pre-mRNA transcript results in secreted and
      membrane-bound forms of the protein. To investigate the role of these two forms
      of human SCF, we targeted an immortalized stromal cell line derived from fetal
      murine homozygous (Sl/Sl) SCF-deficient embryos for gene transfer of various
      human cDNAs encoding SCF. We report that stable stromal cell transfectants can
      differentially process the two forms of human SCF protein product. We also
      demonstrate that both soluble SCF and membrane-bound SCF are active in increasing
      the number of human progenitor cells in the context of stromal cell cultures,
      although in a qualitatively different manner. Hence, the membrane-bound form of
      SCF may play an important role in the cell-cell interactions observed between
      stromal and hematopoietic cells both in vitro and in vivo.

PMID- 1380156
TI  - Human cyclooxygenase-2 cDNA.
AB  - Cyclooxygenase (Cox), also known as prostaglandin (PG) H synthase (EC 1.14.99.1),
      catalyzes the rate-limiting step in the formation of inflammatory PGs. A major
      regulatory step in PG biosynthesis is at the level of Cox: growth factors,
      cytokines, and tumor promoters induce Cox activity. We have cloned the second
      form of the Cox gene (Cox-2) from human umbilical vein endothelial cells (HUVEC).
      The cDNA encodes a polypeptide of 604 amino acids that is 61% identical to the
      previously isolated human Cox-1 polypeptide. In vitro translation of the human
      (h)Cox-2 transcript in rabbit reticulocyte lysates resulted in the synthesis of a
      70-kDa protein that is immunoprecipitated by antiserum to ovine Cox. Expression
      of the hCox-2 open reading frame in Cos-7 monkey kidney cells results in the
      elaboration of cyclooxygenase activity. hCox-2 cDNA hybridizes to a 4.5-kilobase
      mRNA species in HUVEC, whereas the hCox-1 cDNA hybridizes to 3- and 5.3-kilobase
      species. Both Cox-1 and Cox-2 mRNAs are expressed in HUVEC, vascular smooth
      muscle cells, monocytes, and fibroblasts. Cox-2 mRNA was preferentially induced
      by phorbol 12-myristate 13-acetate and lipopolysaccharide in human endothelial
      cells and monocytes. Together, these data demonstrate that the Cox enzyme is
      encoded by at least two genes that are expressed and differentially regulated in
      a variety of cell types. High-level induction of the hCox-2 transcript in
      mesenchymal-derived inflammatory cells suggests a role in inflammatory
      conditions.

PMID- 1380157
TI  - Calcineurin mediates alpha-adrenergic stimulation of Na+,K(+)-ATPase activity in
      renal tubule cells.
AB  - The alpha-adrenergic agonist oxymetazoline increased Na+,K(+)-ATPase activity of
      single proximal convoluted tubules dissected from rat kidney. Activation of the
      enzyme by oxymetazoline was prevented by either the alpha 1-adrenergic antagonist
      prazosin or the alpha 2-adrenergic antagonist yohimbine and was mimicked by the
      calcium ionophore A23187. The effect of oxymetazoline on Na+,K(+)-ATPase activity
      was prevented by a specific peptide inhibitor of calcineurin, as well as by FK
      506, an immunosuppressant agent known to inhibit calcineurin; these results
      indicate that the action of oxymetazoline is mediated via activation of
      calcineurin (a calcium/calmodulin-dependent protein phosphatase). Activation of
      the Na+,K(+)-ATPase by either oxymetazoline or A23187 was associated with a
      greater than 2-fold increase in its affinity for Na+. The results provide a
      biochemical mechanism by which norepinephrine, released from renal nerve
      terminals, stimulates Na+ retention.

PMID- 1380158
TI  - Rapid adaptation of single mechanosensitive channels in Xenopus oocytes.
AB  - Mechanosensitive (MS) channels are expressed in a wide range of cell types and
      have been implicated in diverse functions, including osmoregulation and
      mechanoreception. The majority of previous studies on single MS channels have
      been carried out on nonsensory cells and have dealt with the steady-state
      properties of the channel. Here we measure the dynamic or nonstationary
      properties of the MS channel in Xenopus laevis oocytes. MS channels open
      transiently in response to a step change in suction applied to the membrane
      patch. This adaptive behavior occurs because of a reduction in open channel
      probability rather than a decrease in channel conductance. Double-step suction
      protocols indicate that adapted MS channels can be reactivated by application of
      stronger stimulation, consistent with a change in gating sensitivity rather than
      channel inactivation. Adaptation is highly voltage dependent, being most evident
      at resting or hyperpolarized potentials and absent at strongly positive
      potentials. Neither adaptation nor its voltage sensitivity requires the presence
      of extracellular Ca2+. Adaptation is fragile, dependent on patch history, and can
      be irreversibly abolished by moderate suction applied to the patch while MS
      channel activity is retained. Further suction can abolish MS channel activity
      without compromising the seal. We propose that the selective loss of adaptation
      and MS channel activity is due to different stages of membrane-cytoskeleton
      decoupling caused by the mechanical stresses associated with patch clamp
      recording.

PMID- 1380159
TI  - Yeast FKBP-13 is a membrane-associated FK506-binding protein encoded by the
      nonessential gene FKB2.
AB  - The immunosuppressants FK506 and rapamycin prevent T-cell activation and also
      inhibit the growth of certain strains of the yeast Saccharomyces cerevisiae. It
      has previously been shown that yeast contains a 12-kDa cytosolic FK506-binding
      protein (yFKBP-12), which also possesses peptidylprolyl cis-trans isomerase
      activity, and that fkb1 strains lacking yFKBP-12 are resistant to rapamycin and
      sensitive to FK506. The absence of yFKBP-12 permitted the detection and isolation
      of a second FK506- and rapamycin-binding protein, which is about 13 kDa in size
      (yFKBP-13) and membrane-associated. Purified yFKBP-13 binds FK506 with 15-fold
      lower affinity than yFKBP-12 and has peptidylprolyl cis-trans isomerase activity
      with a similar substrate profile. The sequence of the first 37 N-terminal amino
      acids was determined, and the yFKBP-13 gene (FKB2) was cloned and sequenced. A
      hydrophobic putative signal sequence precedes the N terminus of the mature
      protein. yFKBP-13 most closely resembles the membrane-associated human FKBP-13,
      which also possesses a signal peptide, whereas yFKBP-12 most closely resembles
      human FKBP-12. fkb2 and fkb1 fkb2 mutants are viable and unaltered in their
      sensitivity to FK506, suggesting that yeast possesses an additional target for
      this drug. Furthermore, fkb2 null mutations confer no change in rapamycin
      sensitivity. These findings show that yFKBP-13 and yFKBP-12 have distinct
      functions within the cell.

PMID- 1380160
TI  - Distal transcript of the dystrophin gene initiated from an alternative first exon
      and encoding a 75-kDa protein widely distributed in nonmuscle tissues.
AB  - A transcript generated by the distal part of the Duchenne Muscular Dystrophy
      (DMD) gene was initially detected in cells where the full size 14-kilobase (kb)
      messenger RNA is not found at a significant level. This transcript, approximately
      4.5 kb long, corresponds to the cysteine-rich and carboxyl-terminal domains of
      dystrophin. It begins with a novel 80- to 100-nucleotide exon containing an ATG
      start site for a new coding sequence of 17 nucleotides in-frame with the
      consecutive dystrophin cDNA sequence from exon 63. This result suggests the
      existence of a third promoter that would be localized about 8 kilobases upstream
      from exon 63 of the DMD gene. The distal transcript is widely distributed but is
      absent in adult skeletal and myometrial muscle. It is much more abundant in fetal
      tissues. With an antibody directed against the dystrophin carboxyl terminus, the
      protein corresponding to this transcript was detected as a 70- to 75-kDa entity
      on Western blots. It was found in all tissues analyzed except in skeletal muscle.
      It was not found in lymphoblastoid cells from a Duchenne patient with a complete
      deletion of the dystrophin gene. The role and subcellular localization of this
      protein is not known. It may explain extramuscular symptoms exhibited by some
      Duchenne patients.

PMID- 1380161
TI  - Poly(A) RNA in Escherichia coli: nucleotide sequence at the junction of the lpp
      transcript and the polyadenylate moiety.
AB  - Although it has been known for some time that bacterial mRNA molecules carry
      polyadenylate moieties at their 3' ends, nothing is known about the molecular
      structure of bacterial poly(A) RNA. To define the polyadenylylation site of a
      specific bacterial mRNA, we took advantage of the presence of elevated levels of
      poly(A) RNA in cells of Escherichia coli deficient in exoribonucleases and
      synthesized DNA complementary to polyadenylylated lipoprotein mRNA, encoded by
      the lpp gene, by using avian myeloblastosis virus reverse transcriptase and an
      oligo(dT)-containing primer. The 5'-terminal portion of the cDNA was amplified by
      the polymerase chain reaction and appropriate oligonucleotide primers, and the
      amplified DNA was cloned in pUC18 and subjected to nucleotide sequence analysis.
      Four clones were found to contain the entire 3'-terminal coding region of lpp
      mRNA, with poly(A) attached to either of two sites in the downstream untranslated
      region of the transcript. In one type of clone, the polyadenylate moiety was
      attached at the putative transcription termination site of lpp mRNA, whereas
      other clones lacked the stem-loop structure of the rho-independent transcription
      terminator and the polyadenylate moiety was attached to the residue just
      preceding the terminal stem-loop of the primary transcript. A model for the
      polyadenylylation of bacterial mRNA is proposed in which poly(A) polymerase and
      exonucleases compete for the 3' ends of mRNA molecules.

PMID- 1380162
TI  - Interleukin 2 stimulation of p70 S6 kinase activity is inhibited by the
      immunosuppressant rapamycin.
AB  - Binding of interleukin 2 (IL-2) to its receptor generates intracellular signals,
      including the activation of tyrosine and serine/threonine kinases. In this study
      the activation of the serine/threonine-specific ribosomal protein S6 kinases in
      response to IL-2 was analyzed in the murine T-cell line CTLL-20, a model system
      of IL-2-dependent proliferation. Two major classes of S6 kinases have been
      characterized: the 90-kDa (rsk) family and the 70-kDa family. In response to the
      addition of recombinant IL-2, total S6 kinase activity was increased. This S6
      kinase activity could not be immunoprecipitated by an antiserum specific for S6
      kinases of the 90-kDa family, exhibited a chromatographic behavior characteristic
      of 70-kDa S6 kinases, and was recognized by a 70-kDa S6 kinase-specific
      antiserum. Thus, IL-2 binding to its receptor induces specific activation of the
      70-kDa family of S6 kinases. Rapamycin, a macrolide immunosuppressant that
      inhibits IL-2-dependent proliferation, inhibited IL-2-stimulated 70-kDa S6 kinase
      activity subsequent to early increases in tyrosine kinase activity. These
      findings imply that the targets of rapamycin include molecules involved in the
      activation of 70-kDa S6 kinases. These observations further suggest that S6
      kinases of the 70-kDa family participate in signal transmission pathways
      subsequent to IL-2 binding to its receptor.

PMID- 1380163
TI  - Compartmentalization of excitatory amino acid receptors in human striatum.
AB  - Division of the mammalian neostriatum into two intermingled compartments called
      striosomes and matrix has been established by analysis of enzyme activity,
      neuropeptide distribution, nucleic acid hybridization, and neurotransmitter
      receptor binding. Striosomes and matrix are distinct with respect to afferent and
      efferent connections, and these regions provide the potential for modulation and
      integration of information flow within basal ganglia circuitry. The primary
      neurotransmitters of corticostriatal afferents are excitatory amino acids, but to
      date no correlation of excitatory amino acid receptors and striatal compartments
      has been described. We examined binding to the three pharmacologically distinct
      ionotropic excitatory amino acid receptors, N-methyl-D-aspartate, alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid, and kainate, in human striatum using
      in vitro receptor autoradiography and compared the binding to striosomes and
      matrix histochemically defined by acetylcholinesterase activity. Our findings
      reveal increased binding to N-methyl-D-aspartate receptors and alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid receptors in matrix relative to
      striosomes and increased kainate receptor binding in striosomes relative to
      matrix. These results suggest that afferent input to the two striatal
      compartments may be mediated by pharmacologically distinct excitatory amino acid
      receptor subtypes.

PMID- 1380164
TI  - How the mongoose can fight the snake: the binding site of the mongoose
      acetylcholine receptor.
AB  - The ligand binding site of the nicotinic acetylcholine receptor (AcChoR) is
      within a short peptide from the alpha subunit that includes the tandem cysteine
      residues at positions 192 and 193. To elucidate the molecular basis of the
      binding properties of the AcChoR, we chose to study nonclassical muscle AcChoRs
      from animals that are resistant to alpha-neurotoxins. We have previously reported
      that the resistance of snake AcChoR to alpha-bungarotoxin (alpha-BTX) may be
      accounted for by several major substitutions in the ligand binding site of the
      receptor. In the present study, we have analyzed the binding site of AcChoR from
      the mongoose, which is also resistant to alpha-neurotoxins. It was shown that
      mongoose AcChoR does not bind alpha-BTX in vivo or in vitro. cDNA fragments of
      the alpha subunit of mongoose AcChoR corresponding to codons 122-205 and
      including the presumed ligand binding site were cloned, sequenced, and expressed
      in Escherichia coli. The expressed protein fragments of the mongoose, as well as
      of snake receptors, do not bind alpha-BTX. The mongoose fragment is highly
      homologous (greater than 90%) to the respective mouse fragment. Out of the seven
      amino acid differences between the mongoose and mouse in this region, five
      cluster in the presumed ligand binding site, close to cysteines 192 and 193.
      These changes are at positions 187 (Trp----Asn), 189 (Phe----Thr), 191 (Ser---
      Ala), 194 (Pro----Leu), and 197 (Pro----His). The mongoose like the snake AcChoR
      has a potential glycosylation site in the binding site domain. Sequence
      comparison between species suggests that substitutions at positions 187, 189, and
      194 are important in determining the resistance of mongoose and snake AcChoR to
      alpha-BTX. In addition, it was shown that amino acid residues that had been
      reported to be necessary for acetylcholine binding are conserved in the toxin
      resistant animals as well.

PMID- 1380165
TI  - pH transients evoked by excitatory synaptic transmission are increased by
      inhibition of extracellular carbonic anhydrase.
AB  - Excitatory synaptic transmission has been associated with a rapid alkalinization
      of the brain extracellular space. These pH shifts are markedly increased by
      acetazolamide, an inhibitor of carbonic anhydrase. Although this effect can be
      readily explained by inhibition of extracellular carbonic anhydrase, this enzyme
      has been considered strictly intracellular in the central nervous system. To
      determine whether these alkaline shifts are regulated by extracellular carbonic
      anhydrase, we studied the effects of a membrane impermeant, dextran-bound
      inhibitor of this enzyme. Extracellular alkaline transients, measured with pH
      sensitive microelectrodes, were generated in the CA1 region of rat hippocampal
      slices by repetitive electrical stimulation of Schaeffer collateral fibers or by
      local ejection of glutamate. More direct alkalinizations were elicited by focal
      ejection of NaOH in the vicinity of a pH microelectrode. These pH transients were
      reversibly enhanced by addition of the dextran-bound inhibitor. We conclude that
      there is significant carbonic anhydrase activity in the extracellular space of
      the brain. We postulate that this enzyme functions in the regulation and
      modulation of extracellular pH transients associated with neuronal activity.

PMID- 1380166
TI  - Light-independent developmental regulation of cab gene expression in Arabidopsis
      thaliana seedlings.
AB  - We found a transient increase in the amount of mRNA for four nuclear genes
      encoding chloroplast proteins during early development of Arabidopsis thaliana.
      This increase began soon after germination as cotyledons emerged from the seed
      coat; it occurred in total darkness and was not affected by external factors,
      such as gibberellins or light treatments used to stimulate germination. Three
      members of the cab gene family and the rbcS-1A gene exhibited this expression
      pattern. Because timing of the increase coincided with cotyledon emergence and
      because it occurred independently of external stimuli, we suggest that this
      increase represents developmental regulation of these genes. Further, 1.34
      kilobases of the cab1 promoter was sufficient to confer this expression pattern
      on a reporter gene in transgenic Arabidopsis seedlings. The ability of the cab
      genes to respond to phytochrome preceded this developmental increase, showing
      that these two types of regulation are independent.

PMID- 1380167
TI  - Direct identification of residues of the epidermal growth factor receptor in
      close proximity to the amino terminus of bound epidermal growth factor.
AB  - We have recently developed a kinetically controlled, step-wise affinity cross
      linking technique for specific, high-yield, covalent linkage of murine epidermal
      growth factor (mEGF) via its N terminus to the EGF receptor. EGF receptor from
      A431 cells was cross-linked to radiolabeled mEGF (125I-mEGF) by this technique
      and the 125I-mEGF-receptor complex was purified and denatured. Tryptic digestion
      of this preparation gave rise to a unique radiolabeled peptide that did not
      comigrate with trypsin-treated 125I-mEGF in SDS/Tricine gels but that could be
      immunoprecipitated with antibodies to mEGF. The immunoprecipitated peptide was
      isolated by electrophoresis in SDS/Tricine gels, eluted, and sequenced. The
      sequence was found to correspond to that of a tryptic peptide of the EGF receptor
      beginning with Gly-85, which is in domain I, a region N terminal to the first
      cysteine-rich region of the receptor. Selective loss of signal in the 17th
      sequencing cycle suggests that the point of attachment of N-terminally modified
      125I-mEGF to the receptor is Tyr-101. The data presented here provide
      identification by direct protein microsequencing of a site of interaction of EGF
      and the EGF receptor.

PMID- 1380168
TI  - Spontaneous malignant transformation of melanocytes explanted from Wf/Wf mice
      with a Kit kinase-domain mutation.
AB  - The W/Kit mouse locus, affecting proliferation and survival of pigment cells,
      blood cells, and germ cells, is known to encode a tyrosine kinase growth factor
      receptor and is considered a protooncogene; yet it has not heretofore been
      causally implicated in any malignancies of those cells. The Wf/Wf mutant mouse
      coat comprises viable and inviable melanoblast clones, seen ultimately as
      pigmented and white transverse stripes--the latter more prominent. Judging from
      the pattern, all clones initially expand, and the inviable ones then undergo
      programmed cell death prenatally. To observe skin melanocytes of the viable
      clones during extended proliferation, the cells were explanted from individual
      young mice. An unusually large number of primary explants failed to survive--a
      result consistent with a growth handicap. In 3 of the 10 surviving cell lines,
      many cells spontaneously underwent a series of striking changes with the classic
      features of transformation. The two transformed lines that have been tested by
      grafting to immunosuppressed hosts formed undifferentiated invasive tumors
      compatible with malignant amelanotic melanoma. None of our 52 other melanocyte
      lines of the coisogenic wild-type strain and 13 other natural genotypes have
      become transformed under the same culture conditions. Molecular analysis of the
      Wf gene revealed a single change from wild-type: a point mutation affecting the
      catalytic region in the kinase domain of the Kit protein. The apparent growth
      disadvantage due to the mutation may allow selection for melanocytes mobilizing
      more efficient pathways, thus leading to neoplasia. Production of both viable and
      inviable melanoblast clones is unlikely to be due only to the kinase mutation;
      possibly the degree, duration, and consistency of expression of this locus may be
      controlled by cis elements outside the coding region.

PMID- 1380169
TI  - Detection of a human intracisternal retroviral particle associated with CD4+ T
      cell deficiency.
AB  - A number of non-human-immunodeficiency-virus (HIV) type 1 disorders are
      associated with CD4+ T-cell deficiency and dysfunction. However, the
      etiopathogenesis of CD4+ T-cell immunodeficiency in these disease states remains
      unclear. Human intracisternal retroviral (HICRV) particles were detected in a
      lymphoblastoid cell line exposed to mononuclear cells from a patient with severe
      CD4+ T-cell deficiency without risk factors for HIV infection. Ultrastructurally,
      the HICRV is distinct from HIV-1, HIV-2, human T-lymphotropic virus (HTLV) type
      I, and HTLV-II. Supernatants of activated mononuclear cells showed significant
      reverse transcriptase activity that was predominantly Mn2+ dependent. The
      patient's mononuclear cells were negative for HIV-1, HIV-2, HTLV-I, and HTLV-II
      proviruses as demonstrated by the lack of amplification by PCR. Also, the
      patient's serum was negative for antibodies to HIV-1, HTLV-I, and HTLV-II and for
      HIV-1 p24 antigen; however, serum was positive for antibodies against the HICRV
      as demonstrated by Western blot. Similar HICRV particles were detected in a
      lymphoblastoid cell line exposed to mononuclear cells from the patient's
      daughter, who showed CD4+ T-cell dysfunction. The HICRV may be associated with
      CD4+ T-cell immunodeficiency and dysfunction in patients without risk for HIV-1,
      HIV-2, HTLV-I, and HTLV-II.

PMID- 1380170
TI  - Tachykinin induced inhibition of cardiac intrinsic nerves in isolated atria.

PMID- 1380171
TI  - Evaluation of anti-SIV potential of anti-neoplastic anthracyclines.

PMID- 1380172
TI  - [Biotherapy of cancer].

PMID- 1380173
TI  - [Treatment of carcinoid syndrome with ocreotide (SMS-201-995)].

PMID- 1380174
TI  - [CD34+ cells in the autotransplant of bone marrow and peripheral blood].
AB  - Identification of a glycoprotein expressed on 1.2% of normal bone marrow cells,
      including progenitors of all hematolymphopoietic lineages and pluripotent stem
      cells, has allowed the production of several monoclonal antibodies directed
      against the same structure and included in the new differentiation cluster CD34.
      Availability of these antibodies coupled with techniques of positive selection of
      normal progenitors has opened an interesting and new alternative for purging bone
      marrow. Two of these techniques (avidin-biotin immunoadsorption on column and
      paramagnetic microspheres) have found clinical application and recently data on
      the first series of patients transplanted with CD34+ cells enriched marrows have
      been published. In the area of peripheral blood stem cells transplantation,
      detection by flow cytometry of CD34+ cells in the peripheral blood should replace
      the poorly standardized CFU-GM assay, allowing the best timing of apheretic
      procedures and the easy quantification of stem cells number in a harvest.
      Combination of negative (tumor cell killing) and positive (hemopoietic stem cell
      purification) selection might result in a significant improvement of the purging
      procedure and in a larger application of autologous hematopoietic stem cell
      transplantation for hematological and non-hematological malignancies.

PMID- 1380175
TI  - Treatment of pruritus in cholestatic jaundice by bilirubin- and bile acid
      adsorbing resin column plasma perfusion.
AB  - The efficacy of plasma perfusion through a new anionic resin, BR-350, for
      palliation of intractable pruritus secondary to intrahepatic cholestasis was
      studied in four patients. The treatment was given in a daily 2-h session on 3
      consecutive days and was followed by repeated treatment periods each 3rd to 4th
      week. The patients experienced symptomatic improvement during the first treatment
      period, and the treatment was well tolerated. Adsorption of bile acids across the
      filter was efficient and resulted in a bile acid concentration gradient pre- to
      post-resin of 92%. Thus plasma perfusion through the ion resin BR-350 is an
      effective and safe treatment for symptomatic relief of intractable pruritus in
      cholestatic liver disease and may reduce hospitalization time and increase the
      quality of life.

PMID- 1380176
TI  - TNF alpha-induced expression of endothelial adhesion molecules, ICAM-1 and VCAM
      1, is linked to protein kinase C activation.
AB  - The role of protein kinase C (PKC) in TNF alpha-induced activation of endothelial
      adhesion molecules ICAM-1 and VCAM-1 was analysed. Phorbol myristate acetate,
      which is known to activate PKC, was able to mimic TNF alpha-induced up-regulation
      of ICAM-1 and partly also VCAM-1 expression. Similarly a PKC inhibitor, H7, but
      not another kinase inhibitor, HA1004, inhibited TNF alpha-induced enhancement of
      ICAM-1 expression at both the mRNA and the protein level. Moreover we were able
      to measure a transient PKC activation peak at 16 min after TNF alpha induction in
      endothelial cells analysed by phorbol-dibutyrate binding. These results indicate
      that the TNF alpha-induced effect on the regulation of endothelial adhesion
      molecule expression is at least partly mediated by PKC activation.

PMID- 1380177
TI  - Composition and immunological properties of the protein fraction of A36, a major
      antigen complex of Mycobacterium paratuberculosis.
AB  - TMA (thermostable macromolecular antigens) are major mycobacterial complexes
      present in all mycobacteria. We have purified A36, the TMA complex of M.
      paratuberculosis, the etiological agent of paratuberculosis (Johne's disease),
      and shown by the immune electron microscopy approach its presentation at the cell
      surface. The immunodominance of the A36 complex in Johne's disease was suggested
      by comparative ELISA analysis of infected bovine sera, using either A36 or M.
      paratuberculosis total soluble sonicate as antigens. The cross-reactivity of TMA
      complexes from different mycobacteria was evaluated by immunoenzymometric
      measurements. Percentage of shared epitopes was high for the couple M.
      paratuberculosis-M. avium, and somewhat lower for the couple M. paratuberculosis.
      M. bovis. Immunological kinship between M. paratuberculosis and M. leprae was
      suggested by the finding that out of eleven anti-M. leprae monoclonals, four
      cross-reacted with A36 proteins. The specificity missing at the level of the
      whole A36 complex was sought at the level of its protein components. Comparative
      immunoblot analysis of electrophoresed A36 proteins indicated three of them to
      contain epitopes not shared by M. bovis proteins, and one of them to contain
      epitopes specific with respect to M. avium, M. bovis and M. phlei. The latter
      component, a 34-kDa protein, could be an ideal reagent for a serological test for
      Johne's disease, being immunodominant in infected cattle and endowed with species
      specific epitopes.

PMID- 1380178
TI  - The interactions of gamma delta T cells with extracellular matrix: receptor
      expression and utilization patterns.
AB  - Purified populations and clones of human gamma delta T cells were examined for
      their ability to interact with extracellular matrix (ECM) components. The
      stimulation of these cells with phorbol ester induced cellular adhesion for ECM.
      The adhesion structures for fibronectin and collagen were shown to be members of
      the CD29 integrin family. The expression patterns of beta 1, beta 2 and beta 3
      integrins by these cells were examined. The receptor expression and utilization
      patterns suggest that alpha beta, gamma delta T cells and B cells have similar
      repertoires of adhesion structure.

PMID- 1380179
TI  - Adhesion of activated T lymphocytes to vascular smooth muscle cells and dermal
      fibroblasts is mediated by beta 1- and beta 2-integrins.
AB  - Several studies during recent years have demonstrated the potential for vascular
      smooth muscle cells (SMC) and dermal fibroblasts to participate in immune
      interactions such as antigen presentation and alloreactivity. The molecular
      interactions mediating lymphocyte adhesion to these mesenchymal cells have,
      however, not previously been characterized in detail. In the present study we
      demonstrate ICAM-1 (CD54) expression by cultured human SMC and its up-regulation
      by IL-1, IFN-gamma, and bacterial lipopolysaccharide. Monoclonal antibodies were
      used to define the molecular interactions in the adhesion of 51Cr-labelled T
      lymphoblasts to adherent SMC and fibroblasts. ICAM-1 appeared to mediate adhesion
      of T lymphocytes by binding to the beta 2-integrin CD11a/CD18 (LFA-1) expressed
      by the lymphoblasts. We present evidence for the involvement of at least three
      different mechanisms in the adhesion of activated T lymphocytes to cultured
      fibroblasts. It was found that beta 2-integrin-mediated interaction could only
      account for less than half of the binding activity. The remaining adhesion was
      partly mediated by beta 1-integrins, presumably via VLA-5 since an anti-VLA-5
      antibody and an RGD-containing peptide blocked adhesion to the same degree.
      However, antibodies to beta 1-, beta 2-, and beta 3-integrin subunits added
      together only inhibited adhesion by approximately 50%. The residual adhesion
      could be blocked by inhibition of cell metabolism and was increased by
      stimulation of the lymphocytes with phorbol ester, suggesting involvement of
      other, as yet undefined, adhesion molecules. The molecular interactions between
      lymphocytes and mesenchymal cells demonstrated in this study may have
      implications in several inflammatory conditions such as vasculitis,
      atherosclerosis, and connective tissue diseases.

PMID- 1380180
TI  - The LFA-3 adhesion pathway is differently utilized by superantigen-activated
      human CD4+ T-cell subsets.
AB  - The superantigen SEA binds to MHC class II molecules and activates a large
      fraction of T cells as a result of interaction with particular TCR-V beta
      sequences. MHC class II transfected CHO cells induce a marginal CD4+ T-cell
      proliferation in the presence of SEA. CHO cells transfected with both MHC class
      II and LFA-3 (HLA-DR4/LFA-3 double transfectants) supported a vigorous T-cell
      proliferation and required 1000-fold lower SEA concentration than DR4-transfected
      cells. DR4/LFA-3 double transfectants presenting SEA to CD4+ T cells induced
      large amounts of IFN-gamma, while single DR4 transfectants failed to elicit IFN
      gamma production. CD4+45RA+ naive T cells proliferated much more strongly
      compared with CD4+45R0+ memory T cells when SEA was presented by the DR4/LFA-3
      transfected cells. In contrast, IFN-gamma production was only detected in
      CD4+45R0+ memory cells. The enhanced proliferation by the CD4+45RA+ naive T cells
      was not due to a stronger binding to the accessory DR4/LFA-3 cells. Human CD4+ T
      cell lines mediated a low level of SEA-dependent cell-mediated cytotoxicity
      (SDCC) against DR4 target cells, whereas a strong SDCC was mediated against
      DR4/LFA-3-expressing target cells. These results demonstrate that superantigen
      activated human CD4+ T cells require the adhesion molecule LFA-3 for optimal
      stimulation and that the CD4+ naive and memory T-helper cells are different in
      their response to LFA-3 as an accessory molecule.

PMID- 1380181
TI  - A critical role for conserved residues in the cleft of HLA-A2 in presentation of
      a nonapeptide to T cells.
AB  - The peptide binding cleft of the class I human histocompatibility antigen, HLA
      A2, contains conserved amino acid residues clustered in the two ends of the cleft
      in pockets A and F as well as polymorphic residues. The function of two conserved
      tyrosines in the A pocket was investigated by mutating them to phenylalanines and
      of a conserved tyrosine and threonine in the F pocket by mutating them to
      phenylalanine and valine, respectively. Presentation of influenza virus peptides
      and of intact virus to cytolytic T lymphocytes (CTLs) was then examined. The
      magnitude of the reduction seen by the mutation of the two tyrosines in the A
      pocket suggests that hydrogen bonds involving them have a critical function in
      the binding of the NH2-terminal NH3+ of the peptide nonamer and possibly of all
      bound peptide nonamers. In contrast, the mutations in the F pocket had no effect
      on CTL recognition.

PMID- 1380182
TI  - Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase.
AB  - The immunosuppressant rapamycin inhibited proliferation of the H4IIEC hepatoma
      cell line. Rapamycin, but not its structural analog FK506, also inhibited the
      basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. By
      contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated
      protein (MAP) kinase activity were unaffected by drug. Rapamycin treatment of COS
      cells transfected with recombinant p70 S6 kinase completely inhibited the
      appearance of the hyperphosphorylated form of p70 S6 kinase concomitant with the
      inhibition of enzyme activity toward 40S subunits. Thus, rapamycin inhibits a
      signal transduction element that is necessary for the activation of p70 S6 kinase
      and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP
      kinase.

PMID- 1380183
TI  - Development of microscopic techniques for examining microbial growth in situ in
      food ecosystems.

PMID- 1380184
TI  - Physiology, molecular biology and applications of the bacterial starvation
      response.

PMID- 1380185
TI  - Skeletal fluorosis. An unusual cause of progressive radiculomyelopathy.

PMID- 1380186
TI  - [Effect of sublethal concentrations of abate on biological parameters of Aedes
      aegypti].
AB  - The effect of abate (Temephos) applied at the rate of 0.016, 0.020 and 0.025 mg/l
      on fourth stadium larvae and its effect upon pupae weight, adult weight, ingested
      blood weight and longevity of Aedes aegypti were investigated. The insecticide
      was applied on F2 generation larvae that were fed an artificial diet under
      laboratory conditions, from larvae collected at urban level in Monterrey, N.L.,
      Mexico. In relation to the adult, females were fed with a 10 per cent honey
      solution and rabbit blood for each gonotrophic cycle, while males were fed with
      only a honey solution. The effect of abate showed a trend to reduce the pupae
      weight, adult, weight and ingested blood, and to increase longevity too. Although
      there was not a difference for these variables in the females emerged from larvae
      exposed to the insecticide, the effects were significant in the males. In this
      sex, the weight of pupae and adult decreased by 31 and 33 per cent respectively,
      and longevity increased from 26 to 31 days. Possible advantages and disadvantages
      of these effects are discussed from a control viewpoint.

PMID- 1380187
TI  - Sonographical findings in Whipple's disease. A case report with regard to the
      literature.
AB  - We present a case report of a 60-year-old male patient and subsequently discuss
      sonographical findings in Whipple's disease. This particular patient showed an
      intraabdominal tumorous mass. Symptoms of a malabsorption disorder were absent.
      Computer-assisted tomography and radiological examination could not determine the
      origin of the tumor. Sonography demonstrated a polycyclic hyperechoic mass in the
      root of the mesentery. The small intestine was not distended and showed normal
      peristalsis. Its wall was hyperechoic concentrically thickened. Final diagnosis
      was established from a diagnostic laparotomy showing enlarged lymph nodes and
      distended lymphatic vessels. Based on the literature the described sonographical
      findings seem to be typical in cases of Whipple's disease.

PMID- 1380188
TI  - Laparoscopic cholecystjejunostomy as palliation for obstructive jaundice in
      inoperable carcinoma of pancreas.
AB  - Malignant obstructive jaundice can be palliated by either surgical bypass, which
      has the advantage of long-term patency, or by stent placement, which has the
      advantage of initial lower morbidity and mortality. We describe a technique,
      laparoscopic cholecystjejunostomy, which has the advantage of both. We predict
      that laparoscopic surgery, which has already had a major impact on biliary stone
      surgery, will also have a major impact on interventional endoscopic retrograde
      cholangiopancreatography.

PMID- 1380189
TI  - Detection and significance of alpha granule membrane protein 140 expression on
      platelets collected by apheresis.
AB  - Activation of platelets may be measured by using the monoclonal antibody S12 to
      detect alpha granule membrane protein 140 (GMP-140) antigen expressed only on
      activated platelets. S12 was used to measure activation of apheresis platelet
      concentrates by flow cytometry. Eleven platelet concentrates obtained by one
      method and nine obtained by another were analyzed 4 hours after collection. Means
      +/- 1SD of 25.3 +/- 14.8 percent and 28.9 +/- 11.6 percent, respectively, of
      platelets were found to be activated (range, 4.8-53.1%). Six of the platelet
      concentrates obtained by the second method were filtered. There was a drop of
      17.8 percent (range, 10-25%) in the mean total number of platelets recovered
      after filtration, but there was no difference in the proportion of activated
      platelets measured immediately before and after filtration. The 1-hour
      posttransfusion platelet count increment was obtained after 12 of these apheresis
      platelet concentrates were transfused to eight patients who were not refractory
      from either a clinical or alloimmune standpoint. There was a significant inverse
      correlation between the platelet count increment and the proportion of activated
      platelets in the component (p less than 0.05, r = -.58). These data suggest that
      apheresis platelet concentrates with more activated platelets have a reduced 1
      hour recovery. Filtration did not enhance activation or selectively remove
      activated platelets. Expression of GMP-140 may serve as a useful quality control
      measurement.

PMID- 1380190
TI  - Cytotactin: a morphoregulatory molecule and a target for regulation by homeobox
      gene products.
AB  - Two major lines of research in developmental biology should help us to understand
      the bases of morphogenesis. The first is the analysis of the morphogenetic
      effects of local expression of various adhesion molecules. The second is the
      analysis of cascades of regulatory genes that interact during development. Of
      particular significance are regulatory interactions involving homeobox-containing
      genes which are expressed in a place-dependent manner in the embryo. Success in
      connecting these two lines of research would help to resolve the puzzle of how
      species-specific tissue patterns can arise and be maintained. In this article, we
      focus on cytotactin, a morphoregulatory molecule of the extracellular matrix that
      exhibits sharply restricted spatiotemporal patterns of expression during
      development. Recent experiments indicate the promoter of the cytotactin gene
      contains target regions that appear to respond to homeodomain proteins. These
      observations, and those on other morphoregulatory molecules, suggest a possible
      connection between their effects on cell patterning and control by homeobox
      containing genes.

PMID- 1380191
TI  - Discovering peptide ligands using epitope libraries.
AB  - Epitope libraries are large collections of peptides. Each peptide is displayed on
      the surface of a bacteriophage particle and is encoded by a randomly mutated
      region of the phage genome, thus associating each unique peptide with the DNA
      molecule encoding it. Antibodies and other binding proteins are used to select
      specifically for rare, phage-bearing peptide ligands; sequencing of the
      corresponding viral DNA will reveal their amino acid sequences. Relatively high
      affinity peptides for a variety of peptide- and non-peptide-binding ligates have
      been affinity-isolated from epitope libraries. This technology has been used to
      map epitopes on proteins and to find peptide mimics for non-peptide-binding
      ligates. The current challenge lies in developing epitope library technology so
      that tight-binding peptide ligands can be detected for a wider variety of
      ligates, including those that recognize folded proteins. Should this be
      accomplished, many powerful applications can be envisioned in the areas of drug
      design and the development of diagnostic markers and vaccines.

PMID- 1380192
TI  - Native and non-native intermediates in the BPTI folding pathway.
AB  - Recent studies of the disulfide-bonded intermediates in the refolding of bovine
      pancreatic trypsin inhibitor (BPTI) indicate that the most stable intermediates
      can take on much or all of the structure of the fully folded protein. Native-like
      structure in the intermediates probably causes steric inhibition of direct
      sequential formation of the three disulfides found in the native protein, thus
      accounting for the role of intramolecular rearrangements in the folding mechanism
      of this small protein.

PMID- 1380193
TI  - Hepatoblastomas: an ultrastructural and immunohistochemical study.
AB  - Seven hepatoblastomas were studied by electron microscopy, and four of these were
      studied by immunohistochemistry. Five tumors were purely epithelial, and two were
      mixed epithelial-mesenchymal. They showed a spectrum of cellular differentiation
      ranging from primitive epithelial cells to differentiated cells resembling adult
      hepatocytes. Glycogen, lipid, basal lamina, and canaliculi were present in all
      cases. Mitochondria with large, membrane-bound, amorphous inclusions were present
      in one tumor, and large, complex, basal cell processes were present in two
      tumors. Ultrastructural features most characteristic of hepatocytes were most
      common in fetal type hepatoblastomas. Immunoreactive chromogranin cells were
      present in two tumors, one of which also contained immunoreactive somatostatin
      cells. The somatostatin-positive tumor had cells with granules resembling those
      seen in somatostatin-containing cells of normal pancreas and somatostatin
      containing neuroendocrine carcinomas. Other immunoreactive substances were
      present, including alpha 1-antitrypsin (four cases), vimentin (embryonal cells in
      four cases; fetal cells in three cases), low-molecular weight cytokeratin
      (embryonal cells in three cases; fetal cells in four cases), and high-molecular
      weight cytokeratin (embryonal cells in one case; fetal cells in two cases).
      Osteoidlike material was positive for epithelial membrane antigen, vimentin, and
      S-100 protein.

PMID- 1380194
TI  - Osteogenic sarcoma with epithelial differentiation.
AB  - This case report details an osteogenic sarcoma arising in a vertebra in which
      cytokeratin intermediate filaments were detected immunohistochemically with three
      different antibodies. This feature was present not only in the primary neoplasm
      but also in two local recurrences and a metastasis to the iliac bone. What is
      unique about this primary bone tumor, however, is the structural evidence for
      epithelial differentiation. Ultrastructurally, well-formed desmosomes and
      tonofilaments were present in all four surgically resected specimens. This tumor
      expands the list of soft tissue and bone tumors in which anomalous expression of
      intermediate filaments can occur but, more important, illustrates that changes in
      genetic expression of neoplasia of mesenchymal origin can result in paradoxic
      epithelial differentiation.

PMID- 1380195
TI  - Haematological and clinicochemical blood profiles in slaughter pigs.
AB  - In a cohort study, 40 pig finishing herds were selected: twenty pig herds with a
      low and twenty pig herds with a high prevalence of several pathological lesions
      recorded at slaughter in a six-month period before the start of the study. Blood
      samples were taken from 20 pigs per herd at the end of the finishing period to
      investigate haematological and clinicochemical profiles. There was only a
      significant difference in serum albumin concentration between the low and high
      lesion prevalence groups. There were distinct differences in blood profiles
      between pig herds, but also between batches of pigs within a herd, housed in
      different compartments. Differences between castrated males and gilts were also
      demonstrated with respect to mean values of the blood variables haemoglobin,
      iron, copper, beta-globulin, eosinophils and segmented neutrophils. However, the
      differences were not of a biologically important magnitude. The mean values of
      the blood variables pepsinogen and lymphocytes differed significantly between pig
      herds from the two participating integration groups. Pigs with a higher albumin
      concentration, a lower gamma-globulin concentration, a higher copper
      concentration and a higher creatine kinase activity in serum showed a higher
      daily weight gain.

PMID- 1380196
TI  - Incorporation of soluble antigens into ISCOMs: HIV gp120 ISCOMs induce virus
      neutralizing antibodies.
AB  - Through a process of covalent attachment of palmitic acid, we have incorporated
      recombinant gp120 of HIV strain IIIB into ISCOMs. Rabbits immunized with ISCOMs
      incorporating 10 micrograms gp120 produced high levels of gp120-specific
      antibody, comparable to the response to ten times as much antigen in complete
      Freund's adjuvant. The ISCOM-induced antisera showed virus neutralizing activity
      against the homologous strain, but failed to neutralize two heterologous strains
      of HIV-1. The antisera recognized non-conformationally determined epitopes on
      gp120, and antibody binding to gp120 was affected by glycosylation of the viral
      glycoprotein.

PMID- 1380197
TI  - [Can thermal therapy of ankylosing spondylitis induce an activation of the
      disease?].
AB  - A randomized, open, controlled study was carried out in eight patients with
      spondylitis ankylosans, in a cross-over procedure including total body
      cryotherapy and whole spine paraffin mud packs. The effect of both therapies on
      clinical status and different laboratory data was investigated. No clinical
      changes were seen after either therapy; in contrast, in answering the spine
      function questionnaire patients reported an improvement after cryotherapy and a
      worsening after thermotherapy, but because of the small number of patients no
      positive conclusion was possible. The acute phase proteins (alpha-1-AGP, alpha-1
      ACT, alpha-2-haptoglobin and alpha-2-coeruloplasmin) did not show any changes,
      only CRP increased after thermotherapy and declined after cryotherapy.
      Interesting changes were seen in the glycosylation profile of alpha-1-AGP: after
      thermotherapy an increase of bi-antennary oligosaccharides occurred, observed as
      appearance of a third peak in the affinity immunoelectrophoresis with con A and
      an increase of reactivity-coefficient of alpha-1 and glycoprotein which was also
      seen in the exacerbation of AS. This shows, that an activation of the
      inflammatory process may be possible by thermotherapy (perhaps because of an
      amplification of Il-6 production), but not by cryotherapy. Similar studies should
      be conducted in larger numbers of patients.

PMID- 1380198
TI  - Ultrastructural characterization of substance-P-immunoreactive synaptic terminals
      in the cat's normal and rhizotomized trigeminal subnucleus caudalis.
AB  - Deafferenting injuries often cause transient or permanent physiological
      alterations within the central projection field of affected primary afferent
      fibers. Aberrant sensory perceptions, dysesthesias, and hyperalgesias represent
      the clinical sequelae of such injuries; however, the results of experimental
      deafferentations have been subject to a variety of interpretations (Rodin and
      Kruger, 1984b). Neurochemical studies show an increased sensitivity of partially
      deafferented neurons to substance P (SP). Our previous studies (Hoffmann et al.,
      1991) documented, primarily at the light-microscopic level, a moderate transient
      loss of SP-immunoreactive (SPIR) boutons in the trigeminal subnucleus caudalis
      (Vc)--a loss that seemed to preferentially affect the slightly larger, possibly
      complex boutons with multiple contacts. However, despite the elimination of the
      trigeminal input, the larger boutons reappeared. In the present study, therefore,
      we examined Vc using electron-microscopic immunocytochemistry, in order to
      document these changes over time and to clarify the structure and relationships
      of this population of boutons. SPIR boutons occurred in lamina I and II degrees
      of the substantia gelatinosa of Vc, ranged in size from 1 to 5 microns in
      diameter, and displayed mixed populations of clear and dense-core vesicles. Most
      formed single or multiple axodendritic junctions, but a significant number
      engaged in axoaxonic contacts with both SPIR-labeled and unlabeled terminals. A
      small number appeared to be the central element of a typical glomerulus,
      particularly in lamina II degrees. Three to seven days following an ipsilateral
      retrogasserian rhizotomy, synaptic degeneration was evident in the substantia
      gelatinosa and often involved glomerular terminals. However, most of these were
      SPIR-negative and occurred primarily in lamina II degrees. Those SPIR boutons
      that displayed degenerative features often made single or multiple axodendritic
      contacts, and in some instances were scalloped. By 30 days, most remaining SPIR
      boutons were small, with a lower incidence of contacts; however, some of these
      were axoaxonic. In addition, many SPIR terminals were only very lightly stained-
      a feature not encountered to such an extent in the contralateral Vc. At 45 days,
      complex SPIR boutons were again evident in the field, and some showed densely
      packed vesicles. An increased incidence of clusters of two to four SPIR axoaxonic
      contacts was also observed. Finally, almost all SPIR boutons encountered at this
      stage were intensely stained. It is suggested that these alterations represent a
      compensatory neuroplastic response on the part of overlapping cervical and
      cranial primary afferents to the partial deafferentation resulting from the
      interruption of the trigeminal root.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380199
TI  - An immunohistochemical study on HLA-DR expression in human meningiomas.
AB  - The expression of HLA-DR was examined in 38 cases of meningiomas with the
      streptavidin-biotin immunoperoxidase method using two monoclonal antibodies to
      HLA-DR (LN-3 and TAL-IB5) on formalin-fixed, paraffin-embedded specimens. Similar
      immunoreactivity was obtained with these two monoclonal antibodies. In addition
      to infiltrated lymphoid cells and perivascular macrophages, tumor cells
      themselves showed HLA-DR expression in 16 cases (42%) of meningiomas. The rate of
      HLA-DR-positive cases in the transitional and fibrous subtypes (64% and 67%,
      respectively) was higher than that in the meningotheliomatous subtype (8%).
      Spindle-shaped tumor cells were frequently positive for HLA-DR, whereas few of
      meningotheliomatous cells with plump cytoplasm were positive. Most of HLA-DR
      positive cases showed no or scanty lymphoid cell infiltration, and a few cases
      with marked infiltration of lymphoid cells were variable for HLA-DR expression.
      These findings suggest little correlation between HLA-DR expression of tumor
      cells and the degree of lymphoid cell infiltration, but indicate an aberrant HLA
      DR expression of tumor cells themselves.

PMID- 1380200
TI  - Inclusion bodies in cerebral cortical astrocytes: a new change of astrocytes.
AB  - A unique pathological finding of astrocytes was observed in the brain of a 20
      year-old man who had severe physical and mental retardation. The brain was
      malformed showing micropolygyria in several cortical areas. A large number of
      hypertrophic astrocytes with eosinophilic granular substances in their cytoplasm
      were found throughout the cerebral cortex. Several staining procedures and
      electron microscopical examinations were carried out on these intracytoplasmic
      inclusion. It was found that the appearance and staining character of these
      inclusions were different from other astrocytic changes, especially the Rosenthal
      fiber, described so far. The authors consider that these inclusion bodies in
      cerebral cortical astrocytes represent new pathological changes of astrocytes
      that appear to be associated with malformation of the brain.

PMID- 1380201
TI  - Distribution of 72-kDa heat-shock protein in rat brain after hyperthermia.
AB  - The distribution of the 72-kDa heat-shock protein (hsp72) in rat brain, 24 h
      following in vivo transient hyperthermia (41.5 degrees C, 15 min), was studied
      using immunohistochemistry (n = 22). Tissue sections were also stained with
      hematoxylin and eosin, and with an anti-glial fibrillary acidic protein to
      evaluate neuronal and astrocytic response to transient hyperthermia,
      respectively. hsp72 was observed in glia and endothelial cells throughout brain.
      hsp72 was also found in neurons located in the: dentate gyrus, habenula, and
      hypothalamus, granular layer of the cerebellum and the olfactory area. Our data
      indicate, that hyperthermia causes neuronal expression of hsp72, particularly in
      cerebral neuronal populations which control the neuroendocrine stress response.

PMID- 1380202
TI  - In vivo motor effects of loperamide on the rat urinary bladder.
AB  - Bladder motility recordings were performed in anaesthetized rats and the effect
      of the peripherally active opiate agonist loperamide on urinary bladder function
      was studied. Regional intra-arterial administration of loperamide (0.01-2 mg kg
      1) induced weak bladder contraction per se. Loperamide caused an effective dose
      dependent inhibition of bladder motility induced by regional injection of the
      receptor agonists acetylcholine (ACh) and substance P (SP), as well as by
      peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg
      1) partially antagonized the inhibitory action of loperamide on the nerve
      mediated detrusor contraction. However, the depression of the motor responses
      induced by the receptor agonists ACh and SP was not influenced. It is suggested
      that the demonstrated inhibitory effect of loperamide on bladder motility is
      partially mediated by peripheral opioid receptors. The main non-opioid part of
      the inhibition might be a direct smooth muscle action.

PMID- 1380203
TI  - Reduced expression of CD20 antigen as a characteristic marker for chronic
      lymphocytic leukemia.
AB  - The surface antigens expressed by the cells of chronic lymphocytic leukemia (CLL)
      are well known. Most CLL are monoclonal B-cell lymphoproliferative disorders
      characterized by the coexpression of B-cell antigens and CD5, an antigen present
      predominantly on T cells. Very little attention, however, has been paid to the
      quantitative characteristics of the expression of B-cell antigens in CLL. In this
      study, we used flow cytometry to analyze the expression of CD20, a well-known B
      cell-associated antigen, in lymphocytes from 42 cases of CLL and its tissue
      counterpart, small lymphocytic lymphoma (SLL), and compared the results with
      results obtained from the analysis of 21 follicular lymphomas, 20 hyperplastic
      reactive nodes, and 26 samples of normal peripheral blood. The intensity of CD20
      expression in the CLL/SLL cells was significantly lower than that of B cells in
      the other categories. This antigen expression abnormality does not appear to be a
      universal phenomenon in CLL/SLL, since CD19, another pan-B antigen, was expressed
      in CLL/SLL at levels higher than those in follicular lymphomas and comparable to
      those in reactive lymph nodes. These results indicate that the low CD20
      expression can be used as a marker for CLL/SLL. The few cases exhibiting intense
      CD20 expression may represent a biologically different disease. CLL/SLL cells
      faintly expressing CD20 also show concomitant low CD5 expression in a manner not
      observed in normal CD5-expressing B cells.

PMID- 1380204
TI  - Interleukin-5 in eosinophilic gastroenteritis.
AB  - During a 4-year period a 28-year-old female had 4 episodes of eosinophilia of
      over 10,000/mu 1; these episodes were associated with nausea, vomiting, diarrhea,
      and abdominal pain. On one occasion, she had ascites and pleural effusion which
      contained numerous mature eosinophils. On each occasion, these attacks
      disappeared within several weeks without any specific treatment. A diagnosis of
      eosinophilic gastroenteritis was made. A plasma sample obtained during the
      eosinophilia generated in vitro eosinophilic colonies when added to
      granulocyte/macrophage-progenitor (CFU-GM) cultures without exogenous growth
      factors. Colony formation was inhibited by anti-interleukin-5 (IL-5) antibody but
      not by antibodies toward IL-3, granulocyte colony-stimulating factor (G-CSF) or
      GM-CSF. A high plasma interleukin-5 (IL-5) level was noted when measured by
      enzyme-linked immunosorbent assay, while IL-3, G-CSF, and GM-CSF were
      undetectable. During remission the plasma gave negative results both for colony
      formation and IL-5 level. These results indicate that the eosinophilia of this
      disease is mediated by IL-5.

PMID- 1380205
TI  - Granulocyte-colony stimulating factor corrects granulocytopenia in Felty's
      syndrome.

PMID- 1380206
TI  - Beta-thalassemia intermedia with exceptionally high hemoglobin A2: relationship
      to mutations in the beta-gene promoter.
AB  - Small deletions of the 5' portion of the beta-globin gene that remove the
      promoters but stop 3' to the delta-globin gene are recognized as the sole cause
      of beta-thalassemia with exceptionally high hemoglobin A2 (HbA2) levels. Two
      patients with beta-thalassemia intermedia and exceptionally high levels of HbA2
      (10.4 and 12.0%) were examined. One patient was a combined heterozygote for the 
      88 C----T and a novel -87 C----A mutation, while the other was homozygous for the
      -29 A----G beta(+)-thalassemia mutation. The remainder of the beta genes were
      normal. There was no evidence for deletions involving the 5' portion of the beta
      gene or the region between the beta and delta genes. Gene mapping studies
      excluded the possibility of a beta delta-anti-Lepore hemoglobin gene with beta
      promoters and delta coding sequences. There were no mutations in the promoters of
      the G gamma or A gamma-globin genes that have been associated with the hereditary
      persistence of HbF phenotype. The delta-globin gene promoters were normal from
      codon 17 to position -145 relative to the mRNA capping site. There appears to be
      considerable heterogeneity of HbA2 and HbF levels in patients who are homozygous
      or mixed heterozygotes for mutations in the TATA box and other promoter elements
      of the beta-globin gene. The capacity for proteolysis within the erythrocyte may
      vary among individuals. The authors hypothesize that in the exceptionally high
      HbA2 beta-thalassemia intermedia phenotype, proteolysis of superfluous alpha
      globin chains is less efficient than in patients with customary levels of
      HbA2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380207
TI  - Immunohistochemistry in the differential diagnosis of nodular hidradenoma and
      glomus tumor.
AB  - The histologic distinction between nodular hidradenoma and glomus tumor is an
      occasional difficult diagnostic problem. Both tumors may show circumscribed
      aggregates of uniform epithelioid cells, a myxoid stroma, and variable numbers of
      blood vessels. Especially troublesome are solid cellular hidradenomas without
      duct-like structures and glomus tumors without a vascular pattern. To develop an
      immunohistochemical profile useful in this differential diagnosis, 25 selected
      skin tumors and four normal glomus bodies were studied with antibodies against
      low molecular-weight cytokeratin (CAM 5.2), epithelial membrane antigen (EMA),
      carcino-embryonic antigen (CEA), S-100, and vimentin (VIM). The tumors included
      eight unequivocal hidradenomas, seven unequivocal glomus tumors, and 10
      histologically equivocal cases, originally diagnosed as glomus tumors. In all
      unequivocal glomus tumors and glomus bodies, only VIM was positive. Of the eight
      unequivocal hidradenomas, three were positive for CAM 5.2, EMA, CEA, S-100, and
      VIM; two for CAM 5.2 only; one for CAM 5.2, EMA, and S-100; one for CAM 5.2, EMA,
      and CEA; and one for CEA only. In the histologically equivocal cases, eight were
      positive for VIM only, characteristic of glomus tumor; and two were positive for
      CAM 5.2, EMA, CEA, S-100, and VIM, and were reclassified as hidradenomas. The
      study suggests that morphologic criteria may not always accurately differentiate
      between hidradenoma and glomus tumor and that in equivocal cases
      immunohistochemistry may be useful in the differential diagnosis.

PMID- 1380208
TI  - Porokeratotic eccrine ostial and dermal duct nevus. An abnormally keratinizing
      epidermal invagination or a dilated, porokeratotically plugged acrosyringium and
      dermal duct?
AB  - Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) has been said to
      represent a widely dilated, keratin-plugged acrosyringium and dermal duct. We
      have observed in a case of congenital PEODDN a normal-appearing, acrosyringium
      like duct that traverses vertically the entire length of the parakeratotic
      column. Also, in its lower course, it stained positively for carcinoembryonic
      antigen, while the inner borders of the invagination from which the parakeratotic
      column arose stained negatively. This leads us to suggest that the epithelial
      structure in PEODDN is an abnormally keratinizing epidermal invagination through
      which an acrosyringium-like duct traverses, rather than an abnormally dilated,
      parakeratotically plugged acrosyringium and dermal duct.

PMID- 1380209
TI  - Sperm plasma membrane integrity in fertile and infertile men.
AB  - Sperm plasma membrane characteristics were analysed by a combined method, the HOS
      eosine test (HOS-E test), that consists of the hypoosmotic swelling test (HOS
      test), and the eosine-Y staining. Semen samples were categorized into four groups
      (Normo-, Oligo-, Astheno-, and Oligoasthenozoospermic) and subjected to the
      standard analysis (spermiogram), HOS test, eosine-nigrosine test (reflecting
      sperm viability); and HOS-E test. HOS-E test makes it possible to distinguish
      four groups of spermatozoa: type 1, HOS+/eosine-; type 2, HOS-/eosine-; type 3,
      HOS-/eosine+; and type 4, HOS+/eosine+. Normozoospermic samples showed 61.2 +/-
      1.4% type 1, 9.2 +/- 0.8% type 2, 22.6 +/- 1.1% type 3, and 6.8 +/- 0.6% type 4
      spermatozoa. Oligozoospermic samples showed no significant differences in these
      values, whereas asthenozoospermic samples showed a higher percentage of types 3
      and 4 and a lower percentage of type 1. Oligoasthenozoospermic samples showed
      high percentages of types 2, 3, and 4 and a low percentage of type 1. Sperm
      plasma membrane integrity is a necessary condition for motility and
      fertilization. So, it is not surprising that semen samples with abnormal motility
      showed a HOS-E result indicative of a defective plasma membrane.

PMID- 1380210
TI  - Effects of a DNA-specific fluorochrome, Hoechst 33258, on mouse sperm motility
      and fertilizing capacity.
AB  - DNA specific fluorochrome (Hoechst 33342 and 33258) as non-toxic stains, have
      been widely used to measure cell density and proliferation, detect sperm-egg
      fusion, and observe the development of pre-implantation embryos. It has been
      reported that Hoechst 33342 at a concentration of 10 micrograms ml-1 had
      significant inhibition on embryo cleavage. In this study, we incubated B6D2F1
      mouse sperm and eggs with different concentrations of Hoechst 33258, 0, 1.0,
      10.0, 20.0, 100 micrograms ml-1. We found that: (1) 100 micrograms ml-1 of H
      33258 significantly decreased the sperm motility at 90 min and 4 h. (P less than
      0.05), (2) 20 micrograms ml-1 and 100 micrograms ml-1 of Hoechst 33258
      significantly inhibited mouse fertilization in vitro (P less than 0.05), and (3)
      1.0 micrograms ml-1 and 10.0 micrograms ml-1 Hoechst 33258 had no effect on
      fertilization rate. But when we pre-incubated sperm at 10 micrograms ml-1 Hoechst
      33258 for 90 min, and inseminated oocytes in the medium with same concentration
      of Hoechst 33258, the embryo cleavage was significantly inhibited.

PMID- 1380211
TI  - A MspI polymorphism at the ovine proteolipid protein locus (PLP).

PMID- 1380212
TI  - The nucleotide sequence of boar transition protein 2 (TNP2) cDNA and haploid
      expression of the gene during spermatogenesis.
AB  - A cDNA clone coding for boar transition protein 2 (TNP 2) was isolated from a
      randomly primed cDNA library of boar testis. Sequence analysis revealed an open
      reading frame of 414 bp (corresponding to 138 amino acids), 33 bp of the 5'
      untranslated and about 300 bp of the 3' untranslated region. As compared to TNP 2
      of mouse and rat, similarity with TNP 2 of the boar is approximately 70% at the
      nucleotide level and only about 40% on the basis of amino acid sequence. The
      similarity between boar and bull TNP2 is 77% and 64%, respectively. Northern blot
      experiments with RNA of different boar tissues and in situ hybridization on
      mature boar testis sections revealed testis-specific expression of the TNP 2 gene
      which is restricted to haploid germ cells. Hybridization experiments of boar TNP2
      cDNA with testicular RNA of boar, bull, rat and mouse revealed decreasing
      intensities of the hybridization signals. With human testicular RNA no
      hybridization could be obtained.

PMID- 1380213
TI  - A dinucleotide repeat polymorphism at the glycine- and tyrosine-rich keratin
      locus in sheep.

PMID- 1380214
TI  - [Benefits of regional anesthesia. Anticoagulant treatment and regional
      anesthesia].

PMID- 1380215
TI  - [Benefits and risks of various preventive methods with or without the use of
      dextrans].

PMID- 1380216
TI  - [Benefits and risks of preventive methods with or without the use of
      heparinoids].

PMID- 1380217
TI  - [Does the combination of several prophylactic methods decrease the failures of
      monoprophylaxis?].

PMID- 1380218
TI  - [Can the hierarchy in techniques for the prevention of thromboembolism in
      visceral surgery be determined?].

PMID- 1380219
TI  - [Prevention of thromboembolism in gynecology].

PMID- 1380220
TI  - [Comparison of various methods of prevention of venous thrombosis in
      orthopedics].

PMID- 1380221
TI  - Treatment of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma using
      prednisone with or without the COPBLAM/IMVP-16 regimen. A multicenter study. Kiel
      Lymphoma Study Group.
AB  - OBJECTIVE: To describe the clinical course of patients with angioimmunoblastic
      lymphadenopathy (AILD)-type lymphoma with a sequential treatment with prednisone
      and COPBLAM/IMVP-16. DESIGN: A multicenter, prospective, nonrandomized trial.
      SETTING: University medical centers and community hospitals. PATIENTS: Sixty
      seven patients were registered, 28 were excluded, and 39 patients were evaluable
      for response (median age, 59 years; range, 25 to 82 years) (stages I and II, 10%;
      stages III and IV, 90%; B symptoms, 74%). MEASUREMENTS: Response, survival, and
      relapse. INTERVENTION: Patients initially received prednisone and no further
      treatment if a complete remission was achieved. Relapsing or refractory patients
      were treated with COPBLAM/IMVP-16. Patients with life-threatening tumor
      progression or extension received COPBLAM/IMVP-16 initially. Treatments were
      chosen in accordance with tumor extension and response to prednisone. Treatment
      modalities were not compared. RESULTS: Twenty-eight patients received primary
      prednisone, 18 received secondary prednisone, and 11 received primary
      chemotherapy. The complete response rates (with 95% CIs) were 29% (CI, 12% to
      46%), 56% (CI, 33% to 79%), and 64% (CI, 36% to 92%), respectively. The median
      observation time of surviving patients was 28 months (range, 7 to 53). The median
      overall survival time was 15 months. The probabilities (with 95% CIs) of overall
      survival, event-free survival, and relapse at 36 months were 40.5% (CI, 24% to
      56%), 32.3% (CI, 17% to 47%), and 34.6% (CI, 14% to 56%), respectively. At the
      time of evaluation, 22 of 39 patients had died, 7 of noninfectious complications
      and 14 of infections. CONCLUSIONS: Prednisone with or without COPBLAM/IMVP-16
      treatment in AILD-type lymphoma leads to complete remissions in about half of the
      patients and in long-term, disease-free survival for one third.

PMID- 1380222
TI  - Placental intravillous accumulation of sulfated mucosubstances. A reevaluation of
      so-called hydropic degeneration of villi.
AB  - A histochemical study was performed on 46 placentas showing so-called hydropic
      degeneration of villi. The 46 cases included early abortuses (35 cases),
      incomplete moles (four cases), and complete hydatidiform moles (seven cases). All
      the specimens showed diffuse, positive staining of the distended villous stroma
      with alcian blue at pH 1.2 and 2.5 in the areas containing "hydropic changes."
      The alcian blue positivity was abolished following digestion with hyaluronidase.
      These findings indicate that so-called "hydropic degeneration of villi"
      represents an intravillous accumulation of strongly sulfated mucosubstances
      rather than the result of the accumulation of water. The intravillous
      accumulation of mucosubstances most likely represents a nonspecific stromal
      reaction of the connective tissue of the placenta to a variety of noxious
      stimuli. This finding may have some bearing on the interpretation of the
      physiologic mechanisms involved in placental villous distention, which has been
      largely centered in the past on the premise that the villous swelling was related
      to hemodynamic alterations caused by the accumulation of water.

PMID- 1380223
TI  - Prostate specific antigen and prostatic acid phosphatase measurements for the
      follow-up of patients with prostate cancer.
AB  - The clinical application of 84 prostate specific antigen (PSA) and prostatic acid
      phosphatase (PAP) measurements for the follow-up of 36 patients with treated
      prostate cancer was retrospectively examined by case study. Clinicians use
      several risk markers including serum levels of PSA and PAP to monitor prostate
      cancer progression or stability. These results of PAP and PSA tests were either
      utilized during the patient's clinical assessment or they were disregarded. In
      either case, the results would support or counter the physician's clinical
      decision for patient management. After predictive value analysis it was concluded
      that measurement of PSA alone is more useful than parallel measurements of PSA
      and PAP, when utilized together with standard criteria for assessing treated
      prostate cancer patients.

PMID- 1380224
TI  - Peripheral blood stem cell transfusion for marrow replacement.
AB  - A patient is presented who was treated with ablative therapy for Hodgkin's
      disease and rescued by reinfusion of peripheral blood stem cells (PBSC). The PBSC
      were used because previous therapy (chemotherapy and radiation to the pelvis) had
      resulted in fatty hypocellular marrow which was inadequate for marrow
      transplantation. The PBSC were collected by leukapheresis before and after
      recovery of the marrow from suppression with cyclophosphamide to bring the stem
      cells into cohort cycle and to increase the proportion of stem cells in the
      peripheral blood for collection. The patient showed a successful recovery on a
      time scale somewhat longer cells administered, the absence of stimulation by
      granulocyte macrophage-colony stimulating factor or other cytokine, or potential
      damage done to stromal elements during previous radiation and chemotherapy. The
      patient remains in clinical complete remission, fully engrafted, more than one
      year since his autologous transplant.

PMID- 1380225
TI  - Hyperthermic potentiation of bleomycin cytotoxicity in the presence of Bacillus
      thuringiensis subsp. israelenis delta-endotoxin.
AB  - We previously reported that a 25-kDa Bacillus thuringiensis subsp. israelensis
      (BTI) delta-endotoxin potentiated the antitumor activity of bleomycin (BLM) in
      both in vitro and in vivo systems. We report here a characteristic hyperthermic
      synergy toward the cytocidal activity of BLM in the presence of BTI endotoxin in
      cultured L1210 cells. Cytocidal gain, i.e., the ratio of the IC50 of BLM in the
      absence versus the presence of BTI delta-endotoxin, reached ca. 20 at 40 degrees
      C, suggesting that a more effective heat-BLM combination treatment may be
      achieved in the presence of BTI delta-endotoxin.

PMID- 1380226
TI  - Heterogeneity and multiple expression of intermediate filament proteins, S-100
      protein and neuron specific enolase in skin mixed tumor.
AB  - Intermediate filament proteins, keratin (KL1, PKK1, K8.12) and vimentin, S-100
      protein alpha and beta subunits and neuron specific enolase were evaluated
      immunohistochemically to determine their distribution patterns in the tumor
      components of mixed tumor of skin. Keratin proteins were distributed widely in
      tumor epithelial cells or modified myoepithelial (MME) or neoplastic
      myoepithelial (NME) cells. Luminal cells of the tubulo-ductal structure of the
      tumor mass showed positive staining of KL1 and PKK1 keratins and an infrequently
      positive reaction of MoAb K8.12. The outer or basal tumor cells were
      characterized by coexpression of K8.12 keratin, vimentin, S-100 protein and
      infrequently neuron specific enolase reactivity. Heterogeneity of keratin
      distribution was seen in tumor epithelial cells. MME cells or NME cells of skin
      mixed tumor showed coexpression of keratin and vimentin, and multiple expression
      of intermediate filament proteins, S-100 protein and neuron specific enolase.
      Hyaline and chondroid changed cells stained intensely to vimentin and S-100
      proteins, as well as to neuron specific enolase. The authors evaluate the
      histogenesis of skin mixed tumor in relation to epithelial and myoepithelial
      cells of the sweat gland and their immunohistochemical findings.

PMID- 1380227
TI  - Prognostic value of cell proliferation in breast cancer as determined by
      proliferating cell nuclear antigen (PCNA) immunostaining.
AB  - A series of 175 biopsies from primary tumours were subjected to immunostaining
      for proliferation cell nuclear antigen (PCNA) and histopathological analysis for
      prognostic factors in 175 women with breast cancer followed up for nine years. In
      normal breast epithelium, only occasional nuclei were positive for PCNA. In
      breast carcinomas, the fraction of nuclei positive for PCNA showed considerable
      intratumoural variation, usually being highest at the invasive tumour margins.
      The fraction of positive nuclei was significantly related to histological grade
      (p less than 0.001), histological type (p = 0.049) and tumor recurrence (p =
      0.01). The fraction of positive nuclei predicted recurrence-free survival (p =
      0.007) and overall survival (p = 0.0158) in univariate analysis. In the
      multivariate analysis including also the standard prognostic factors, the PCNA
      positivity predicted recurrence-free survival (p = 0.004) and overall survival (p
      = 0.030) independently. The results show that the light microscopic assessment of
      the growth fraction as determined by PCNA immunolabeling has independent
      prognostic value in breast carcinomas like some other (e.g. S phase fraction,
      mitotic index, Ki-67) previously characterized proliferation indices.

PMID- 1380228
TI  - Determination of estrogen and progesterone receptors in endometrial
      adenocarcinomas. Comparison between dextran-coated charcoal and immunoenzymatic
      methods on curettage biopsies.
AB  - Estrogen receptors (ER) and progesterone receptors (PR) were determined on
      curettages from women with endometrial adenocarcinoma. The results obtained with
      the enzyme immunoassay (EIA) and the dextran-coated charcoal (DCC) assay were
      compared. A highly significant correlation was obtained between these methods for
      the ER measurement (Rs = 0.91). For PR determination, the Rs value between EIA
      and DCC assay was 0.57 and the mean value of PR-DCC is significantly higher than
      the mean value of PR-EIA. These results suggest that EIA is a suitable method for
      ER measurement. For PR determination on curettage material the DCC assay seems
      more accurate than EIA.

PMID- 1380229
TI  - (-)-2'-deoxy-3'-thiacytidine is a potent, highly selective inhibitor of human
      immunodeficiency virus type 1 and type 2 replication in vitro.
AB  - The (-)-enantiomer of 2'-deoxy-3'-thiacytidine (3TC) was found to be a potent and
      selective inhibitor of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV-2)
      in vitro. We determined its antiviral activity against a number of laboratory
      strains of HIV-1 and HIV-2 in a range of CD4-bearing lymphocyte cell lines (mean
      50% inhibitory concentration [IC50] range, 4 nM to 0.67 microM). 3TC was also
      active against a range of HIV-1 strains in peripheral blood lymphocytes (mean
      IC50 range, 2.5 to 90 nM). The IC50 for cytotoxicity in seven lymphocyte cell
      cultures, including human peripheral blood lymphocytes, ranged from 0.5 to 6 mM.
      3TC had no detectable antiviral activity against a range of other viruses or in
      cells chronically infected with HIV-1 or HIV-2. The effects of time of addition
      of the compound and varying the multiplicity of infection on the antiviral
      activity of 3TC were determined. The results showed that 3TC is a potent and
      selective inhibitor of HIV-1 and HIV-2 replication in vitro.

PMID- 1380231
TI  - Expression of cytokeratins in granulosa cell tumors and ovarian carcinomas.
AB  - One of the problems in histopathology of ovarian tumors is differential diagnosis
      between the poorly differentiated carcinomas and granulosa cell tumors of the
      sarcomatoid type. Hence we evaluated the expression of various cytokeratins (CK 1
      19; CK 10, 13, 14, 15, 19; CK 8, 18, 19; CK HMW 1, 5, 10, 11; CK 8; CK 1-19
      Stahli; CK AE1/AE3) immunohistochemically in 53 ovarian malignancies (11 of them
      poorly differentiated carcinomas and 12 granulosa cell tumors). CK HMW was not
      detected in granulosa cell tumors, and in only half of the carcinomas. AE1/AE3
      was expressed by more than 90% of ovarian carcinomas but by one granulosa cell
      tumor only. The other keratins we investigated showed higher expression rates in
      granulosa cell tumors and/or lower expression rates in ovarian carcinomas. We
      think that cytokeratin immunohistochemistry is of value in differentiating
      between granulosa cell tumors and ovarian carcinomas.

PMID- 1380230
TI  - Macrophages in melanocytic naevi.
AB  - Whereas the inflammatory infiltrates of malignant melanoma have been widely
      investigated, little is known about the infiltrates accompanying benign
      melanocytic naevi. Using monoclonal antibodies directed against HLA-DR antigens,
      the CD1 antigen, the transferrin receptor and functionally divergent macrophage
      subpopulations, frozen fresh material of 87 melanocytic naevi (MN), ten primary
      cutaneous melanomas (PCM) and ten samples of normal skin were studied. Compared
      with normal skin, abundant HLA-DR+ cells were found in the stroma of MN
      equivalent to the quantity present in PCM. In MN we found higher numbers of
      dermal CD1+ dendritic cells compared with PCM and normal skin. There were more
      macrophages that expressed the transferrin receptor or the antigens 27E10, RM3/1
      and 25F9 in MN than in normal skin but fewer than in PCM. No significant
      differences were found between congenital MN (n = 40), common acquired MN (n =
      27) and dysplastic MN (n = 20) macrophage subpopulations. Also, no correlations
      were evident between macrophage infiltrates and naevus location or patients' age.
      Our data show that potential melanoma precursors among melanocytic naevi cannot
      be identified by the pattern of macrophage infiltrates.

PMID- 1380232
TI  - Distribution of peptide-containing nerve fibers in the gastric musculature of
      patients undergoing surgery for gastroesophageal reflux.
AB  - The distribution of nerve fibers and cell bodies reactive for the peptides
      enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide were
      studied in biopsies of external muscle taken from the gastric body and antrum of
      17 patients undergoing surgery for gastroesophageal reflux, and in regions of
      healthy stomach resected as part of gastric cancer operations. The results were
      correlated with preoperative measurements of liquid and solid emptying from the
      stomach in the patients with gastro-esophageal reflux. In three cases, no delay
      was detected in either liquid or solid emptying, and the distribution of peptide
      immunoreactive fibers in the external muscle was similar to that of healthy
      muscle. In 14 cases, the emptying of either liquids or solids or both was
      delayed, and in eight of these clearcut changes in the distribution of peptide
      immunoreactive fibers occurred. In six cases, the number of enkephalin
      immunoreactive fibers was fewer than normal in the biopsy from the gastric body
      (in one of these samples the number of substance P-immunoreactive fibers was also
      reduced). In another cae, the number of substance P-immunoreactive fibers in the
      antrum was reduced, and in another the number of vasoactive intestinal peptide
      and neuropeptide Y-immunoreactive fibers in the antral biopsy was reduced. It is
      concluded that in patients with gastroesophageal reflux who have delayed gastric
      emptying, a proportion demonstrate abnormalities of the peptide-immunoreactive
      fibers that innervate the gastric external muscle.

PMID- 1380233
TI  - Two-dimensional electrophoresis and densitometric analysis of solubilized bovine
      sperm plasma membrane proteins detected by silver staining and radioiodination.
AB  - Bovine sperm plasma membranes were extracted with deoxycholate and subjected to
      two-dimensional gel electrophoresis. Proteins were visualized either by silver
      staining or autoradiography using 125I. When 1.5-2.0 micrograms of protein
      extract was applied to the first-dimension get, 250 spots could be detected by
      autoradiography. Thirty micrograms of protein was required to obtain spot
      visualization using silver strain, revealing more than 500 spots on the gel.
      These data establish the limit under which two-dimensional electrophoresis can be
      used in conjunction with flow cytometric sorting of sperm for the analysis of
      possible sex-specific membrane differences. The necessity of orienting sperm as
      they past the laser in the cell sorting system reduces throughput; thus, the
      number of sperm sorted within a given time is limited. It is suggested that
      autoradiography will allow the flow cytometer to be used in a time-efficient
      manner. Longer sorting times would be required to obtain sufficient sample to
      analyze total protein composition.

PMID- 1380234
TI  - Immunocytochemical localization of bioregulatory peptides in marmoset testes.
AB  - Immunocytochemical localization of neuropeptides (beta-endorphin, substance P,
      arginine vasopressin, oxytocin), pituitary hormones (adrenocorticotropin,
      prolactin, growth hormone, follicle stimulating hormone (FSH), gonadal inhibin,
      gastrin, and human chorionic gonadotrophin (hCG)) was carried out in marmoset
      testis during development. Both intensity of immunostaining and distribution of
      these peptides in testicular compartments viz. seminiferous tubules and Leydig
      cells changed dramatically during development. In vitro biosynthesis of inhibin
      and FSH was increased by hCG, whereas prolactin (5 micrograms) and prostatic
      inhibin peptide suppressed the synthesis of these hormones.

PMID- 1380235
TI  - Analysis of urinary protein by immunoblot method using unconcentrated urine in
      preeclampsia.
AB  - In order to investigate the renal change in preeclampsia, molecular weight and
      specific protein analyses in unconcentrated urine were performed by the
      immunoblot method. Urine samples were taken from 34 preeclamptic cases (pure
      type), including 20 severe cases. Polypeptide profiles of urine consisted of four
      patterns: low MW (L) pattern (tubular damage), high MW (H) pattern (glomerular
      damage), high and low MW (HL) pattern, and middle MW (M) pattern. The incidences
      of the HL, H, L, and M patterns were 26.5%, 14.7%, 11.8%, and 47.1%,
      respectively. The HL pattern was found more frequently in severe proteinuria than
      in mild proteinuria. High incidences of the HL and H patterns were found in the
      hypertensive group. Larger amounts of IgM, fibronectin, IgG, and beta 2
      microglobulin in urine were confirmed using specific antibodies. Our results
      suggest that the immunoblot method makes it possible to differentiate glomerular
      and tubular damages and to evaluate the severity of renal damage in preeclampsia
      using unconcentrated urine.

PMID- 1380236
TI  - A binding profile of manganese to the nucleus of rat liver cells, and manganese
      induced aberrations in thyroid hormone content and RNA synthesis in the nucleus.
AB  - Manganese (Mn) is accumulated in the nuclear and mitochondrial fractions when
      excess Mn is administered. However, little is known with respect to the behaviors
      of Mn in nuclei. In the present study, rats were given excess Mn and the nuclei
      were purified from liver cells by differential and sucrose gradient
      centrifugations. Being subjected to equilibrium dialysis with a radioactive 54Mn,
      the binding capacity of Mn in nuclei from the control rat was five-fold higher
      than BSA, which was used as a reference protein; and the capacity of 54Mn-binding
      rose in the nuclei from the Mn-treated animals in comparison with those from the
      control. On the analyses of nuclear materials with partial solubilization,
      sepharose column chromatography and HPLC, there were two major fractions which
      associated with a lot of Mn; one fraction was of large molecules of DNA, and the
      other fraction seemed to be peptides with small molecular weights. Therefore, Mn
      may open up a superhelical structure of DNA to provide more negatively charged
      phosphate moiety as a binding-site for a positively charged Mn. The results also
      disclosed a possible aberration in biological functions due to excess Mn in
      nuclei; the apparent association constant of triiodothyronine, a physiologically
      active thyroid hormone, to the nucleus was reduced by 75% and the uptake of 14C
      labelled orotic acid to a newly synthesized RNA in the liver was severely
      inhibited.

PMID- 1380237
TI  - [Catalytic activity of immune complexes of peroxidase and its conjugates with
      cortisol in Aerosol OT reverse micelles].
AB  - Conjugates containing 1, 6 or 11 cortisol molecules per peroxidase molecule were
      obtained by the reaction of the N-hydroxysuccinimide ester of cortisol 3-O
      carboxymethyloxime (COR) with horse-radish peroxidase (HRP). Activities of the
      peroxidase conjugates and their immunocomplexes with antibodies against cortisol
      in the orthophenylenediamine oxidation in reversed Aerosol OT micelles in heptane
      at various hydration degrees of the micelles (omega 0) were studied. Catalytic
      activities of HRP and its conjugates, on one hand, and of the immunocomplexes of
      HRP with anti-HRP and the conjugates with antibodies against cortisol, on the
      other hand, differed significantly and depended in a different manner on the
      hydration degree of AOT micelles. These differences became the basis of a
      homogeneous enzyme-immunoassay of cortisol in the reversed micelles of AOT in
      heptane.

PMID- 1380238
TI  - [The exposure of the population to toxic substances in the interior of motor
      vehicles--the example of benzene].
AB  - The exposure of the population to benzene is caused in the first place by
      emissions of the motor-vehicle traffic. The air pollution concentrations in main
      traffic routes and in the sphere of influence of industrial plants amount to 5-30
      micrograms Benzene/m3 in the course of the year. In indoor air about 6-12
      micrograms/m3 are detectable, in the interior of motor-vehicles between 50 and
      200 micrograms/m3. Smoking raises the individual burden significantly; in
      contrast food and drinking water amount only for a small part of the total intake
      of benzene. In rural areas with low outdoor-air concentrations the main source of
      burden can be the intake of benzene during the use of motor-vehicles. Despite the
      relatively low carcinogenic potency of benzene but because of the unfavourable
      exposure conditions and the comparatively high concentrations measures for the
      reduction of benzene in fuel should be taken immediately.

PMID- 1380239
TI  - MHC-binding peptides for immunotherapy of experimental autoimmune disease.
AB  - It is now well accepted that T helper cells play a central role in the induction
      and maintenance of autoimmune disease. Many experimental models have emphasized
      this fact and have illustrated the efficacy of therapeutic strategies aimed at
      disrupting T cell recognition of autoantigens. Antibodies directed at either
      class II proteins of the major histocompatibility complex (MHC) or CD4 accessory
      molecules have been universally successful. However, the potential use of
      antibodies for therapy in humans is complicated by host anti-globulin and anti
      idiotype responses. An alternative approach to anti-MHC blockade with antibodies
      is peptide blockade of MHC molecules. In addition, peptides may be used as
      agonists of autoantigens in order to modulate the autoimmune response. The use of
      synthetic peptides for therapy is an innovative yet relatively unexplored
      approach and will be the subject for discussion in this article.

PMID- 1380240
TI  - The forces driving autoimmune disease.
AB  - There are two classes of autoimmune disease, organ-specific and non-organ
      specific or systemic. That cells producing autoantibodies are selected by antigen
      is strongly suggested by the presence of mutations and high affinity antibody. T
      cells are pivotal in all forms of autoimmunity as evidenced by the therapeutic
      benefit of anti-T-cell monoclonals such as anti-CD4, and the frequent development
      of high affinity IgG autoantibodies. The production of anergic T-cells by the use
      of non-depleting anti-CD4 in the presence of antigen is discussed with particular
      reference to its potential for immunological intervention in autoimmune disease.
      It is possible to identify T-cell epitopes in organ-specific autoimmunity using
      pathogenic T-cell clones or hybridomas to identify the peptide sequences which
      are reactive. Antigen-specific therapy may ultimately be based on such peptide
      epitopes. The specificity of the T-cells in systemic autoimmunity is still
      obscure, but there is some evidence that reactivity with certain germ-line
      idiotypes can lead to the development of systemic autoimmunity. The possibility
      of stimulating B-cells specific for auto-antigens such as DNA becomes feasible if
      a complex of antibody and DNA is taken up by these specific B-cells and processed
      idiotype is presented to T-helpers specific for those idiotype epitopes. Evidence
      is presented that there may be pre-existing defects in the target organ in
      certain organ-specific disorders, and the evidence for a glycosylation defect in
      the IgG in patients with rheumatoid arthritis is explored. It is noted that the
      spouses of probands with rheumatoid arthritis is explored. It is noted that the
      spouses of probands with rheumatoid arthritis also tend to have this
      glycosylation defect and this raises the possibility of an effect due to an
      environmental factor, such as a microbial infection. Molecular mimicry of
      autoantigens by microbes can stimulate autoreactive cells by their cross
      reactivity. It is emphasized that cross-reaction which gives rise to the priming
      of autoreactive T-cells could give rise to the establishment of a chronic
      autoimmune state. In animals with normal regulatory immune systems, such induced
      autoimmunity is ultimately corrected and it is only in animals where there are
      defects in regulation, that autoimmunity persists. Thus, there are many factors
      giving rise to autoimmunity, and the diseases are rightly regarded as
      multifactorial in origin.

PMID- 1380241
TI  - Interleukin-6 and its receptor in autoimmunity.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine which acts on a wide variety
      of cells, regulating immune response, acute phase reaction and hematopoiesis. In
      accordance with its pleiotropic functions, IL-6 is indicated to be involved in
      the pathogenesis of several diseases including autoimmunities, lymphoid
      malignancies and inflammations. An elevated level of IL-6 is demonstrated in
      patients with rheumatoid arthritis and cardiac myxoma, which can explain symptoms
      of these diseases, such as autoantibody production and increase in acute phase
      proteins. Therefore, inhibitors of IL-6 production or IL-6 receptor-mediated
      signal transduction may be used for treatment of IL-6-related diseases. The IL-6
      receptor system consists of two membrane proteins, a ligand-binding chain (IL-6R)
      and a non-ligand-binding signal transducer, gp130, both of which belong to the
      cytokine receptor family. Binding of IL-6 to IL-6R triggers the association of IL
      6R and gp130, and gp130 in turn transduces the signal. A nuclear factor for
      controlling IL-6 gene expression (NF-IL6) is also involved in the transcriptional
      regulation of various acute-phase protein genes. IL-6-stimulation of hepatocytes,
      through modification of pre-existing NF-IL6 protein, leads to binding of NF-IL6
      to IL-6-responsive elements and activation of acute-phase protein genes. NF-IL6
      is shown to recognize the enhancer core sequence of several viruses, suggesting a
      possible relationship of virus infection and IL-6 expression.

PMID- 1380242
TI  - SRC-related proto-oncogenes and transcription factors in primary human T cells:
      modulation by cyclosporin A and FK506.
AB  - Activation of T lymphocytes induces transcription of genes encoding for
      lymphokines. Interleukin-2 (IL-2) gene expression is controlled transcriptionally
      by the cooperative activity of specific trans-activating factors that bind to the
      IL-2 enhancer. Cyclosporin A (CsA) and FK506 inhibit the production of IL-2 in T
      lymphocytes at the level of gene transcription. A member of the src gene family,
      the lymphocyte-specific protein tyrosine kinase, p56lck, has been implicated in
      IL-2 production. CsA was found not to inhibit lck gene expression, nor the
      activity of the lck gene product. However, CsA and FK506 inhibit the appearance
      of DNA binding activity of factors that bind to the NF-AT and AP-1 sites in the
      IL-2 enhancer. Since the induction of NF-AT and AP-1 is induced by the same
      stimuli that stimulate IL-2 production, these results indicate that the
      immunosuppressant action of CsA and FK506 is exerted at the level of these trans
      activating factors.

PMID- 1380244
TI  - Towards peptide immunotherapy in rheumatoid arthritis: competitor-modulator
      concept.
AB  - By the introduction of single-amino acid substitutions in well-defined T cell
      epitopes of autoimmunogenic proteins, e.g., mycobacterial heat shock protein
      (hsp60) in adjuvant arthritis (AA) and myelin basic protein (MBP) in experimental
      allergic encephalomyelitis (EAE), efficiently blocking MHC binding peptides were
      selected. Despite the finding that a substituted variant of epitope 180-188 of
      hsp60 was 'blocking' not only responses of the 180-188 specific arthritogenic T
      cell A2b, but also responses of the MBP specific encephalitogenic T cell Z1a, in
      vivo testing of this competitor peptide revealed a very prominent disease
      inhibitory activity in AA but not in MBP-induced EAE. The selectivity of this
      peptide in suppressing the disease in which native 180-188 appears to be of
      critical relevance, offers the possibility of achieving disease specific
      immunological intervention. Based on the results collected so far, it seems that,
      in vivo in addition to blocking activity, a variant peptide itself could trigger
      responses that confer protective activity in AA. Such combined activities may
      well be required for achieving full in vivo inhibition of a disease in which
      multiple distinct epitopes may play a role, possibly through presentation by more
      than one MHC product.

PMID- 1380243
TI  - Molecular mode of action of cyclosporin and FK506 in human thymocytes.
AB  - The molecular mode of action of cyclosporin, three of its non-immunosuppressive
      analogs, N-methyl-l-alanyl cyclosporin, acetyl cyclosporin and cyclosporin S3,
      and of FK506 was studied in primary cultures of human thymocytes. Nuclear factors
      derived from thymocytes activated with phorbol myristate acetate and concanavalin
      A were tested for their ability to bind to a synthetic radiolabelled probe
      corresponding to the NF-AT region (-285 to -255) of the IL-2 gene. Binding was
      observed, and it was inhibited by CsA (100 ng/ml), while the analogs at ten-fold
      higher concentrations (1000 ng/ml) were only partially inhibitory. CsA in
      combination with FK506 inhibited binding of nuclear factors at the NF-AT site,
      and acted in concert.

PMID- 1380245
TI  - Immunointervention in autoimmune diseases from cellular selectivity to
      autoantigen specificity.
AB  - Immunosuppressive agents have proved to be remarkably successful in controlling
      the course of a growing number of autoimmune diseases. The usual occurrence of
      relapses when the treatment is stopped and the persisting risk of long term
      complications linked to over-immunosuppression have prompt the search for new
      approaches, aiming at more rapid and selective intervention and earlier onset of
      therapy. New chemicals and monoclonal antibodies presently represent the main
      clinical orientations, while at the experimental level major efforts are directed
      towards peptide therapy (autoantigen, T cell receptor) and tolerance induction.

PMID- 1380246
TI  - Molecular mechanisms of immunosuppression.
AB  - The immunosuppressive drug cyclosporin A (CsA, Sandimmun, SIM) is currently being
      evaluated in a variety of autoimmune disorders with some remarkable successes.
      Despite the wide empiric application of CsA, the precise mechanism of action of
      this drug remains elusive. To identify the molecular mode of action of CsA in the
      process of T cell activation, we have compared the biological profile of
      cyclophilin-binding cyclosporin analogues (CBCA), which lack immunosuppressive
      properties, with CsA. We have found that CsA binding to its intracellular
      receptor (cyclophilin) is required but not sufficient for immunosuppression.
      Moreover, inhibition of the peptidyl-prolyl cis-trans isomerase activity of
      cyclophilin does not seem to be relevant for the inhibitory effects of CsA. In
      analogy to the immunosuppressants FK506 and rapamycin, a specific structure at
      the 'effector' domain of the CsA molecule different from the immunophilin
      'binding' domain determines the biological activity. Overall, a significant
      understanding of the structure-activity relationship of CsA has emerged. This
      will have a major impact on the identification of the precise mechanism of action
      of CsA and its side effects in the process of immunosuppression.

PMID- 1380247
TI  - Relationship between the expression of differentiation-specific keratins 1 and 10
      and cell proliferation in epidermal tumors.
AB  - In normal epidermis, the expression of keratins 1 and 10 is associated with the
      loss of proliferative capacity and the onset of terminal differentiation.
      Keratins 1 (K1) and 10 (K10) are commonly expressed in the differentiating layer
      of benign tumors, but are lost during progression from the benign to the
      malignant state in skin carcinogenesis. Active gene constructs of mouse K1 and
      K10 were introduced into papilloma and carcinoma cell lines derived from
      keratinocytes to analyze the consequences of the expression of these keratins on
      the organization of the endogenous cytoskeletal network and on the mitotic
      activity of the recipient cells. Exogenous K1 integrated into the preexisting
      keratin K5/K14 network of both SLC-1 carcinoma and 308 papilloma cells. The
      formation of a recombinant cytoskeleton was more restricted for K10 than for K1
      and appeared to be related to a requirement for cessation of cell division before
      K10 could integrate. The integration of exogenous K1 filaments into the
      endogenous keratin network was compatible with sustained proliferation of SLC-1
      carcinoma cells in vitro. However, the exogenous gene was not expressed in tumor
      grafts in vivo. In contrast, stable K1 or K10 transfectants could not be selected
      in 308 cells, suggesting that benign tumor cells expressing suprabasal keratins
      cannot sustain proliferation.

PMID- 1380248
TI  - Alloimmune thrombocytopenia: in utero treatment by high doses of intravenous
      gamma globulins.
AB  - The authors report successful in utero treatment by high doses of intravenous
      gamma globulins in a case of neonatal alloimmune thrombocytopenia. Early
      diagnosis allows an appropriate management: fetal blood sampling as early as 20
      weeks of gestation; in case of fetal thrombocytopenia, treatment by intravenous
      gamma globulin (1.0 g/kg/b.w.) each week during 8 weeks or more; ultrasound
      screening of in utero hemorrhage, particularly intracranial hemorrhage; fetal
      blood sampling before delivery at term and in utero transfusion of platelet
      antigen negative in case of persistence of fetal thrombocytopenia.

PMID- 1380249
TI  - Effect of gamma-interferon on the expression of major histocompatibility complex
      class I and II gene products in neural cells isolated from the developing human
      fetal peripheral nervous system.
AB  - The effect of gamma-interferon (gamma-IFN) on the expression of major
      histocompatibility complex (MHC) gene products was examined in the developing
      human fetal peripheral nervous system. RNA blot hybridization analysis of total
      RNA isolated from human fetal dorsal root ganglia (DRG) neural cell populations
      cultured in vitro for 5 days resulted in the detection of both MHC class I- and
      class II-specific RNAs. As determined by protein immunoblotting and fluorescence
      activated flow cytometry, MHC class I and II proteins were also readily
      detectable in cultured human fetal DRG neural cell populations 5 days after
      isolation. In addition, treatment of 3-day human fetal DRG neural cells with
      gamma-IFN (100 U/ml; 48 h) resulted in a marked increase in the level of MHC
      class I- and class II-specific RNA and protein without inhibiting the
      proliferation of the neural cell population. These results suggest that changes
      in the levels of selected cytokines such as gamma-IFN may alter the ability of
      specific neural cell populations present in the developing human nervous system
      to participate in immune reactions by alteration of MHC class I and II antigen
      expression which may lead to perturbation in glial cell function and ultimately
      to nervous system dysfunction in general.

PMID- 1380250
TI  - A simple procedure for recovering the denaturing effect of methylmercury in
      agarose gel electrophoresis.
AB  - A simple and rapid procedure for recovering the denaturing effect of
      methylmercuric hydroxide in agarose gel electrophoresis is described. The
      procedure consisted of the treatment of the commercial methylmercuric hydroxide
      solutions with Amberlite, a mixture of anion- and cation-exchange resins. This
      treatment greatly improved the resolution of RNA species when fractionated by
      electrophoresis through agarose-CH3HgOH slab gel.

PMID- 1380251
TI  - Reverse staining of sodium dodecyl sulfate polyacrylamide gels by imidazole-zinc
      salts: sensitive detection of unmodified proteins.
AB  - We report here a modification to copper and zinc chloride staining methods. The
      introduction of a preincubation of the gels, prior to metal staining, with 0.2 M
      imidazole allows the formation of a homogeneous background for the subsequent
      precipitation of the metal chelate. The reported imidazole-zinc staining takes
      minutes, resulting in reproducible staining patterns with only slightly lower
      sensitivity than silver staining. The method allows efficient recovery of
      proteins from previously stained gels and is compatible with immunoidentification
      on Western blots and also with amino acid analysis and NH2-terminal sequence
      analysis of transferred proteins. A mechanism is proposed to explain the observed
      improvement in reproducibility and sensitivity of imidazole preincubation to zinc
      staining.

PMID- 1380252
TI  - Use of in vitro-transcribed RNAs as immobilized targets during RNA:RNA
      hybridization.
AB  - We describe the use of in vitro-transcribed complementary RNAs as filter-bound
      targets during nuclear run-on analyses. Use of these single-stranded reagents in
      high-stringency RNA:RNA hybridizations increases signal-to-background
      hybridization seen using DNA targets and allows efficient measurement of
      transcriptional rates across genes in either direction.

PMID- 1380253
TI  - Acidic fibroblast growth factor accelerates dermal wound healing.
AB  - Acidic fibroblast growth factor (aFGF) is a potent mitogen in vitro for many
      cells of ectodermal and mesodermal embryonic origin including skin-derived
      epidermal keratinocytes, dermal fibroblasts and vascular endothelial cells. Based
      on the mitogenic activity for these skin-derived cells, we tested the ability of
      topically applied aFGF to promote healing of full-thickness dermal wounds in
      healthy rodents. Low doses of aFGF can produce almost a two-fold maximum
      acceleration in the rate of closure of full-thickness dermal punch biopsy wounds
      in young healthy mice and rats. The mitogen also produces a 3 to 4 day
      acceleration in the time to complete closure in rats. Quantitative
      histomorphometric analysis of wound tissue shows that aFGF induces a marked
      stimulation of angiogenesis, granulation tissue formation and the growth of new
      epithelium, but does not promote dermal contraction. Application of aFGF to
      linear incisions in rat skin produces a transient increase in wound tensile
      strength accompanied by enhanced cellularity and deposition of collagen.
      Therefore, aFGF functions as a pharmacological agent that can accelerate dermal
      wound healing in rodents and could act therapeutically to promote dermal tissue
      repair in humans.

PMID- 1380254
TI  - The vascular endothelial growth factor proteins: identification of biologically
      relevant regions by neutralizing monoclonal antibodies.
AB  - Angiogenesis plays critical roles in organ development during embryonic and fetal
      life, wound healing and in a variety of pathological conditions. Vascular
      endothelial growth factor (VEGF) is a secreted growth factor specific for
      vascular endothelial cells which induces angiogenesis in vivo. To gain a better
      understanding of the physiological role of VEGF, we have generated and
      characterized four murine monoclonal antibodies (mAbs) using the 165 amino acid
      species of recombinant human VEGF as immunogen. These mAbs (A3.13.1, A4.6.1,
      B4.3.1 and B2.6.2) belong to IgG1 isotype and have high affinities for VEGF
      (dissociation constants range from 2.2 x 10(-9) to 4 x 10(-10) M). Two different
      epitopes were detected with these mAbs. One epitope is recognized by mAbs A3.13.1
      and B2.6.2, and the other recognized by mAbs A4.6.1 and B4.3.1. The epitope
      recognized by mAb A4.6.1 appears to be continuous while mAb B2.6.2 recognizes a
      discontinuous epitope. MAb A4.6.1 recognized three species of VEGF generated by
      alternative splicing, VEGF121, VEGF165 and VEGF189 while mAb B2.6.2 binds only
      VEGF165 and VEGF189. Results using an in vitro bovine adrenal cortex endothelial
      cell proliferation assay, in in vivo vascular permeability assay and an in vivo
      embryonic chicken angiogenesis assay showed that mAb A4.6.1 has potent VEGF
      neutralizing activities. MAb A4.6.1 was shown to block the binding of VEGF to its
      receptor(s) suggesting the inhibitory mechanism for VEGF activities. These well
      defined mAbs should be very powerful tools to understand the structure-function
      relationship of various domains of VEGF and may have therapeutic potential.

PMID- 1380255
TI  - Differentiation and activation associated expression of IL-6 and IL-6 receptors
      in U-937 monocytic cells: relationship to the expression of CD14.
AB  - Activated monocytes play an important role as producers of IL-6 during
      inflammation and immune response. We show that during monocytic differentiation
      of U-937 cells, induced by phorbolester (PMA), IL-6 mRNA expression was
      transiently up-regulated and IL-6 protein was secreted into the medium. In
      contrast, differentiation induced by VitD3 or Retinoic acid (RA) did not lead to
      an increase in the IL-6 expression. Thus, IL-6 expression does not seem to be
      associated with monocyte differentiation per se. However, U-937 cells terminally
      differentiated by VitD3, rapidly responded to bacterial lipopolysaccharide (LPS)
      induced activation by IL-6 expression and secretion. In cells, differentiated by
      PMA, the IL-6 expression was super-induced after activation by interferon-gamma
      (IFN-gamma) and LPS. The capacity of U-937 cells to respond to LPS activation by
      IL-6 expression was associated with the expression of CD14 and some serum
      components(s) were a prerequisite for a successful LPS induction. The IL-6R
      expression was down-regulated during monocytic differentiation of U-937 cells. In
      the terminally differentiated U-937 cells, the expression of IL-6R could be
      induced after activation by IFN-gamma and to a lesser extent by LPS, suggesting a
      mechanism by which activation positively regulates the response to IL-6 in
      macrophages.

PMID- 1380256
TI  - Hematopoietic growth factors as adjuncts to antiretroviral therapy.
AB  - Anemia and neutropenia are common complications of HIV infection. Antiretroviral
      therapy with zidovudine exacerbates bone marrow suppression by inhibiting
      proliferation of blood cell progenitor cells. In addition, treatment for
      opportunistic infections or malignancies can involve the use of myelosuppressive
      drugs. As a consequence, severe anemia and neutropenia can result, thereby
      limiting the utilization of antiretroviral drugs. Since antiretroviral therapy
      can increase survival, drugs that ameliorate myelosuppression are important
      adjuncts in the treatment of HIV-infected patients. Three hematopoietic growth
      factors are effective in the treatment of anemia or neutropenia. In four placebo
      controlled trials, erythropoietin (EPO) at doses up to 600 U/kg/wk decreased mean
      transfusion requirements by 37%, increased mean hematocrit by 4.5% and corrected
      anemia in the majority of patients receiving zidovudine over a 12-week period. In
      a separate study, granulocyte colony-stimulating factor (G-CSF) corrected
      leukopenia and isolated neutrophil defects in 22 patients with AIDS without
      altering HIV expression. When erythropoietin was added to the regimen, combined G
      CSF and EPO corrected both anemia and leukopenia and lessened subsequent
      zidovudine toxicity. Similarly, granulocyte macrophage-colony-stimulating factor
      (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients
      with HIV infection. In controlled and uncontrolled trials, GM-CSF also appears to
      reduce toxicity from zidovudine, ganciclovir, and antineoplastic therapy. New
      combinations of hematopoietic stimulants are being used to decrease the toxicity
      from combination antiretroviral therapy with alpha interferon and cytotoxic
      chemotherapy in the treatment of AIDS-related malignancies.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1380257
TI  - Production of human monoclonal antibodies specific for conformational and linear
      non-V3 epitopes of gp120.
AB  - Three IgG1 human monoclonal antibodies (MAbs) directed against conformational
      epitopes of the gp120 envelope protein of HIV-1 were produced, as was a single
      human MAb to a linear epitope spanning amino acids 487-509 in the C-terminal
      portion of gp120. All three conformation-dependent MAbs reacted optimally with
      recombinant gp120 (rgp120) captured on plastic via its carbohydrate moieties with
      Concanavalin A. These MAbs were able to block the interaction between recombinant
      CD4 (rCD4) and rgp120; they were also able to achieve 50% neutralization of HTLV
      IIIB and MN strains of HIV-1 in a concentration range of 0.5-12.8 micrograms/mL.
      The MAb to the linear determinant is the first reported human MAb specific for
      the immunodominant portion of gp120; this MAb was most reactive with rgp120 when
      it was coated directly on plastic. It could neither inhibit rCD4-rgp120 binding
      nor neutralize either HTLV-IIIB or MN. The binding affinities of the four human
      MAbs for rgp120 in solution, reflected by their dissociation constants (Kd),
      ranged from 0.5 x 10(-8) to 7.5 x 10(-8) M.

PMID- 1380259
TI  - Delineation of immunoreactive, conserved regions in the external glycoprotein of
      the human immunodeficiency virus type 1.
AB  - Immunization of mice and rats with purified external glycoprotein gp120 from two
      divergent human immunodeficiency virus type 1 (HIV-1) isolates resulted in the
      development of seven hybridomas secreting monoclonal antibodies able to recognize
      regions of gp120 which are common among divergent strains of HIV-1. These
      monoclonal antibodies cross-reacted with env glycoproteins from one African
      (Rutz), one Haitian (RF), and three North American viral isolates, namely IIIB,
      MN, and 451 by either immunoblot or radioimmunoprecipitation assays. All
      recognized denatured gp120 in immunoblots with the exception of one which
      required a conformationally intact glycoprotein for reactivity. The gp120
      epitopes identified by these antibodies were mapped by screening of an env gene
      library in the lambda gt11 expression system. Three out of four epitopes were
      found to reside in the amino-terminal half of gp120 (Cys9 to Cys35, Thr44 to
      Glu72 and Val108 to Met130), the other was located in the middle region (Thr221
      to Ser255). By virtue of their extent of cross-reactivity these reagents might
      provide a unique resource for the detection of new viral isolates related to HIV
      1.

PMID- 1380258
TI  - Characterization of a mouse/human chimeric monoclonal antibody (C beta 1) to a
      principal neutralizing domain of the human immunodeficiency virus type 1 envelope
      protein.
AB  - A chimeric mouse-human antibody (C beta 1) was constructed that recognized the
      principal neutralizing domain (PND) of human immunodeficiency virus type 1 (HIV
      1) gp120. The constant (C) immunoglobulin regions (C gamma 1 and C kappa) of a
      mouse monoclonal antibody, 0.5 beta, were substituted for the human C gamma 1 and
      C kappa by recombining the DNA modules encoding variable or C regions. The DNA
      constructs were then transfected into X63 Ag8.653 myeloma cells. A clone with a
      high production of the chimeric antibody (C beta 1) was selected. This antibody
      was tested for its biological activity against HIV-1. It bound to the surface of
      HTLV-IIIB-infected cells and reacted with gp120/160 with equal affinity and
      specificity to that of the parental 0.5 beta murine monoclonal antibody in a
      Western blot assay. Neutralization and/or enhancement of HIV infection were
      evaluated with C beta 1 and 0.5 beta. Both C beta 1 and 0.5 beta neutralized cell
      to-cell infection and cell-free virus infection by HTLV-IIIB. Antibody-dependence
      enhancement of HIV infection was not observed with either C beta 1 or 0.5 beta in
      the presence or absence of human complement. Antibody-dependent cell-mediated
      cytolysis (ADCC) and antibody-dependent complement-mediated cytolysis (ACC) were
      observed with C beta 1 but not with the parental 0.5 beta. These findings suggest
      that the neutralizing antibodies to PND may neutralize but not enhance HIV
      infection. Furthermore, the high levels of ACC and ADCC shown against HIV
      infected cells by C beta 1 indicate that the clinical application of such
      monoclonal antibodies may be possible.

PMID- 1380260
TI  - Study of viral replication in HIV-1-infected CEM T-cell subclones which are
      reduced in their ability to form syncytia.
AB  - The derivation of ethyl-methanesulfonate (EMS) mutagenized subclones from the CEM
      T-cell line has been described. These clones expressed CD4 and bound soluble
      gp120, however, two of the generated clones were markedly reduced in their
      ability to form syncytia after infection with either gp160-vaccinia vector or
      cell-free human immunodeficiency virus type 1 (HIV-1). Here, we asked at what
      stage(s) viral infection is blocked in these cells. Polymerase chain reaction
      (PCR) analysis revealed that at 6 and 72 h postinfection with HIV-1, cells of the
      syncytia-deficient clones expressed markedly reduced amounts of viral-specific
      DNA compared with cells of the parental line or the syncytia-positive clones.
      Long-term cultures revealed a marked delay in the appearance of reverse
      transcriptase (RT) activity in the supernatants of these subclones when compared
      with the parental line and viral replication did not lead to massive cell death.
      Syncytia formation in HIV-1-infected cultures of the syncytia-deficient subclones
      was enhanced by tumor necrosis factor alpha (TNF alpha) when added 24 h
      postinfection. In contrast, pretreatment with TNF alpha for 48 h followed by
      washing and infection of the cells with HIV-1 augmented syncytia formation of the
      syncytia-positive subclones, but not of the syncytia-negative subclones. Thus,
      the EMS-mutagenized subclones may provide a tool to study host cell factors
      required for the establishment of a productive HIV-1 infection and responsiveness
      to TNF alpha.

PMID- 1380261
TI  - Identification of two neutralizing and 8 non-neutralizing epitopes on simian
      immunodeficiency virus envelope using monoclonal antibodies.
AB  - Ten new monoclonal antibodies (MAbs) to SIV envelope were produced and
      characterized. Using a panel of 28 MAbs, 10 antibody binding sites on SIV
      envelope protein were identified. Seven sites were located in gp120 and three in
      gp41. Five sites in gp120 and two in gp41 were defined by overlapping peptides.
      The remaining two sites on gp120 and one on gp41 were distinguished by
      competition binding assays but could not be defined by overlapping peptides,
      suggesting that they were discontinuous or conformational epitopes. Five of the
      28 MAbs consistently and reliably neutralized the infectivity of SIVmac251. Two
      of these bound to a peptide (aa171-190) in the V2 region. The remaining three
      MAbs bound to a conformational epitope on gp120. These two neutralizing epitopes
      on SIV are analogous to similar epitopes recently described in HIV-1. In
      contrast, three MAbs binding to the V3 region of SIV failed to neutralize
      infectivity, suggesting that this region in SIV may by functionally different
      from the V3 loop in HIV-1.

PMID- 1380262
TI  - Identification of broadly reactive continuous antigenic determinants of simian
      immunodeficiency virus glycoproteins.
AB  - The env polyprotein sequences of several simian immunodeficiency virus (SIV)
      isolates were analyzed using computer algorithms designed to predict
      immunologically reactive protein segments. Peptides corresponding to predicted
      epitopes were synthesized and employed in peptide enzyme-linked immunosorbent
      assay (ELISA) screening of serum panels from experimentally infected macaques, as
      well as naturally infected, asymptomatic mangabeys and African green monkeys.
      Several of the peptides are recognized by a high percentage of antisera from each
      panel of monkeys indicating that they represent group-specific antigenic
      determinants of SIV. Several type-specific determinants also were identified.
      These peptides may be a useful tool for studying the kinetics of SIV glycoprotein
      specific immune responses produced by infected and vaccine-protected monkeys at
      the epitope level.

PMID- 1380263
TI  - Identification of a neutralizing domain in the external envelope glycoprotein of
      simian immunodeficiency virus.
AB  - Two murine monoclonal antibodies (MAbs), designated MATG2014 and MATG2033, were
      generated. They are reactive with the external envelope glycoprotein gp130 of the
      simian immunodeficiency virus of macaque monkey (SIVmac251), and display a cell
      free virus neutralizing activity in vitro. In addition, MATG2014 cross-reacts
      with HIV-2Rod gp140. Epitope mapping of these MAbs was performed by screening and
      SIVmac peptide library expressed in yeast and confirmed using synthetic peptides.
      MATG2014 and MATG2033 recognize two overlapping epitopes localized in an 18
      residue domain between amino acid 171 and 188 of the SIVmac251 gp130. Sera from
      experimentally SIV-infected macaques are immunoreactive with this neutralizing
      domain. Sequence comparison with related SIV and HIV-2 viral strains indicates a
      low variability of this region, consistent with the cross-reactivity of MATG2014
      with HIV-2Rod gp140. This domain should then be considered in designing
      experimental vaccines.

PMID- 1380264
TI  - The pathophysiology of pain.
AB  - The two most common types of pain presented to dentists are acute orofacial pain
      and chronic craniofacial pain. This article presents some newer concepts in the
      understanding of the pathophysiology of pain. Pain perception, modulation and
      transmission are briefly described, followed by a discussion of the physiological
      and biochemical aspects of chronic and recurrent facial pain.

PMID- 1380265
TI  - [Chronic, post-traumatic scaphoid-lunate instability treated by scaphoid-lunate
      arthrodesis].
AB  - The authors after a review of certain elements of the physiology and
      pathophysiology of the scapho-lunate couple, report a series of 10 patients
      presenting a post-traumatic scapho-lunate instability stabilized by scapho-lunate
      bone graft in order to obtain scapho-lunate arthrodesis. The bone fusion was
      obtained 5 times out of 10, 3 times complete and 2 times by an incomplete bony
      bridge. In 5 cases, bone fusion was not evident, a fibrous non-union probably
      occurred which maintained the correction. Nevertheless, the overall results were
      considered good in 9 out of 10 cases with only one poor result. The outcome with
      a mean follow-up of 4 years did not show any arthritic changes. The authors
      consider that scapho-lunate stabilization with an interposed bone graft is a good
      method which can ensure good stabilization and good clinical results.

PMID- 1380266
TI  - [Lesions of the ligaments associated with distal fractures of the radius. 58
      intraoperative arthrographies].
AB  - Intracarpal ligamentous tears and fractures of the radius often have a similar
      mechanism. For instance, no prospective studies have defined the real incidence
      of such associations, which are not antagonistic. The authors performed a
      systematic operative wrist arthrogram during distal radius fractures in a group
      of 58 patients with a mean age less than 50 years. Such a population was at low
      risk of degenerative ligamentous tears. Triangular fibrocartilage complex was
      torn in two-thirds of all types fractures. Extra-articular radius fractures were
      associated with an intracarpal ligamentous tear in 25% and always a luno
      triquetral lesion type. In contrast, intra-articular and radius styloid fractures
      were frequently associated with a scapho-lunate lesion.

PMID- 1380267
TI  - [Distal ischemia of the upper limb due to obliteration of the ulnar artery at the
      wrist: surgical treatment].
AB  - So-called "Raynaud's distal ischaemic phenomena of the upper limb may be
      responsible for disabling functional impairement and even lesions requiring
      amputation of one or several fingers. The ulnar artery is usually involved in
      these phenomena because of its anatomical position and its importance in the
      blood supply of the hand and the fingers. The authors present three clinical
      cases of distal ischaemia of the upper limb due to obliteration of the ulnar
      artery at the wrist, treated by microsurgical vein graft. A review of the
      literature revealed only 23 well documented cases of this type of treatment, i.e.
      10% of all treatment options, which gave 95 to 100% of favourable results. The
      three patients in our series, reviewed after 2, 3 and 5 years, were considered to
      be cured. Although the severity of the disease can be evaluated by the clinical
      course, arteriography appears to be the key examination for diagnosis, prognosis
      and choice of treatment. However, two practical attitudes are recommended to
      avoid the risk of progression towards digital necrosis: when the symptoms are
      chronic, arteriography is indicated in the case of resistance to medical
      treatment or immediately in the case of unstable symptoms. The diagnosis of
      occlusion of the ulnar artery at the wrist then justifies treatment by
      microsurgical vein graft; when the symptoms are acute, treatment should preserve
      as much as possible the palmar and digital ulnar arterial blood supply.

PMID- 1380268
TI  - [Chemical burns of the hand and upper limb: therapeutic approach].
AB  - Clinical burns of the hand and the upper limb induce various lesions, depending
      on the degree of tissue penetration and their aggressive properties; strong
      acids, particularly sulfuric acid and strong bases such as lime are the most
      dangerous. The clinical attitude should be surgical. Early skin excision, as
      economic as possible, will be indicated, taking into account the difficulties of
      precisely determining the limit between normal and necrotic tissues; fluorhydric
      acid, rapidly dissociates into H+ and Fl- which, because of its small size, will
      rapidly penetrate deeply into the blood circulation. Moreover this molecule has
      the peculiar power to provoke marked hypocalcemia able to cause death, due to its
      avidity for Ca++, with a subsequent cellular lysis. There is currently an
      increase in domestic accidents, as fluorhydric acid is present in several
      scouring solutions; in every case of chemical burns, the main treatment remains
      emergency washing with water possibly, followed by a specific neutralization;
      skin excision must be the rule when the power of neutralization is limited,
      because of the risk of progressively deepening lesions due to the presence of
      residual scouring solutions.

PMID- 1380269
TI  - [Techniques of continuous nerve block at the level of the wrist].
AB  - Functional treatment without pain is a condition for good results after
      operations at gliding structures (tendons) or periarticular structures. Good
      analgesia of the arm and hand is obtained with continuous axillary nerve blocks.
      Often there is concomitant paralysis and active motion is not possible. We
      therefore use continuous nerve blocks at the wrist. The technique of these blocks
      is described in the paper. We use a prefabricated catheter set to introduce the
      polyethylene catheter and to place it near the nerve as in single shot wrist
      block. This technique for continuous analgesia of the hand can be used for
      functional treatment after tenolyses, arthrolyses and stable osteosyntheses of
      fingers. Median, radial and ulnar nerves can be blocked all at the same time or
      alone.

PMID- 1380270
TI  - [Three rare fractures of the radius associated with an ulnar slipped epiphyses].
AB  - Over a period of 7 years, three adolescent boys had an associated diaphyseal
      fracture of the distal third of the radius with separation of the distal ulnar
      epiphysis. The fracture involved towards early epiphysiodesis of the growth plate
      of the distal ulna leading to a shortened ulna without any severe functional
      disability. The mechanisms of injury and complication are described. The
      treatment of this associated lesion is classical emergency, but the radiological
      follow-up must be extended in time because the growth potential of the forearm
      bones is important even during adolescence. The onset of a growth disturbance
      requires rapid surgical epiphysiodesis of the radius to prevent the development
      of deformity.

PMID- 1380271
TI  - ["Congenital" dislocation of the radial head. A bilateral case developing around
      the age of ten].
AB  - Dislocation of the head of the radius has important repercussions on pronation
      supination, elbow stability and on the wrist joint. In the absence of a history
      of trauma, this anomaly is generally considered to be "congenital". Few authors
      have described the progressive acquisition of this dislocation during growth. The
      case of a 20 year old man is presented, corresponding to initial subluxation
      which gradually evolved towards dislocation of the head of the radius at about
      the age of 11 years. This type of dislocation appears to be related to abnormal
      growth of the proximal radial epiphysis, responsible for repercussions on the
      humero-radial articular relations and on the anatomy of the upper extremity of
      the radius. The patient was treated by ulnar osteotomy at the age of 17 years
      according to Hirayama's technique, when he was probably already too old. Surgical
      correction of the subluxation of the head of the radius at an earlier age would
      probably have been preferable.

PMID- 1380272
TI  - [A case of primary intraneural ossification of the ulnar nerve].
AB  - The authors report a case of ossification of the ulnar nerve at the elbow. The
      dense bone tissue spread into the interfascicular space while the epineurium and
      the fasciculi were undamaged. The pathological tissue was removed and the patient
      recovered. No similar report has been found in the literature.

PMID- 1380273
TI  - [Traumatic avulsion of the triceps brachialis tendon. A case report].
AB  - We report a triceps tendon avulsion (less than 40 cases reported in the medical
      literature). Clinical and radiological signs are: 1) Impossible elbow extension
      against gravity, 2) Flecks of avulsed osseous materiel from the olecranon on
      lateral elbow radiograph. Immediate surgical repair always produces good results.

PMID- 1380274
TI  - [Pseudoaneurysm of the common digital artery].
AB  - Palmar aneurysms are very rare. The authors report a case of pseudoaneurysm in an
      18 year old waiter. The mechanism was puncture by a chip of porcelain. The
      diagnostic errors, clinical and pathological criteria are recalled and the
      literature concerning this problem is reviewed.

PMID- 1380275
TI  - [Primary malignant lymphoma localized in the trunk of the ulnar nerve at the
      elbow. A case report].
AB  - The subject of this report is the exceptional observation of an ulnar nerve
      syndrome in the right elbow induced by the intra and extra neural development of
      a primary malignant lymphoma. The patient is a man of sixty-eight. The syndrome
      evolved over one year. The electromyogram showed marked slowing of the conduction
      speed on the ulnar nerve. The operation unabled us only to carry out a partial
      biopsy resection. Complementary chemotherapy was then carried out making a
      survival of two years and seven months possible without any sign of recurrence or
      other sites. We have only been able to locate two other published cases of
      primary malignant lymphoma developing on a nerve trunk and more precisely in on
      the level of the sciatic nerve. No other case has been described in a nerve trunk
      in the upper limb.

PMID- 1380276
TI  - [Lesions of the distal radio-ulnar joint in compression-extension fractures of
      the distal extremity of the radius. Six cases with associated anterior
      dislocation of the ulnar head].
AB  - A particular course of markedly displaced wrist fracture associated with complete
      dislocation of the distal radio-ulnar joint and a real anterior dislocation of
      the ulnar head is related. In 5 other identical cases, treatment with external
      fixation achieved a more favourable result. These 6 cases concerning a particular
      type of wrist fracture, and a review of the literature, led us to suggest a
      potential pattern of TFCC lesions. Finally, from an anatomical classification of
      the ulnar compartment, we propose some therapeutic guidelines concerning the
      ulnar side for more common fractures.

PMID- 1380277
TI  - Whipple's disease, familial Mediterranean fever, adult-onset Still's disease, and
      enteropathic arthritis.
AB  - Whipple's disease is a rare multisystem disorder of infectious etiology. Efforts
      to culture the responsible organism have been unsuccessful. Nucleotide sequencing
      and amplification of bacterial 16S ribosomal DNA revealed the organism to be most
      similar to bacteria of the Rhodococcus, Streptomyces, and Arthrobacter genera.
      Several clinical studies of the long-term use of colchicine for the treatment of
      familial Mediterranean fever demonstrate its utility for symptom control and
      prevention of complications by amyloidosis in both adults and children. Normal
      growth, development, and subsequent fertility were seen in children treated with
      colchicine. Adult-onset Still's disease has previously been thought to have a
      generally good outcome, although some patients develop chronic arthritis and
      disability. No markers have been available for prognosis. A study of 62 patients
      revealed the presence of polyarthritis, root joint involvement, and rash at
      initial presentation to be associated with a poorer outcome. Enteropathic
      arthritis may be seen as a complication of both Crohn's disease and ulcerative
      colitis. The onset of peripheral arthritis coincides with or follows the onset of
      bowel symptoms in most cases, whereas spondylitis may precede the onset of
      inflammatory bowel disease by years. HLA-B27 is present in 50% to 75% of cases of
      spondylitis. No HLA association with inflammatory bowel disease or peripheral
      arthritis has been consistently found.

PMID- 1380278
TI  - The cytokine-like action of substance P upon B cell differentiation.
AB  - B cells respond to a variety of effector molecules that can induce these cells to
      differentiate. One such molecule is the neuropeptide, substance P (SP). Previous
      studies have demonstrated the presence of SP receptors on lymphocytes while
      limited studies have been able to demonstrate the biological significance of
      their expression. SP has been shown to enhance IgA and IgM responses by Peyer's
      patch and splenic B cells. A limitation of these studies was that the direct
      effect of SP upon B cells was not ascertained, suggesting these B cells were
      stimulated via alternate mechanisms. To this end, evidence here will be discussed
      that SP can directly interact with clonal B lymphoma cells and highly purified
      splenic B cells. The data implicate SP as a late-acting B cell differentiation
      factor that requires an additional triggering mechanism to initiate the B cell
      differentiation process.

PMID- 1380279
TI  - Modulation of the mRNAs encoding substance P and its receptor in rat macrophages
      by LPS.
AB  - Numerous soluble factors and their receptors contribute to the regulation of
      immune responses. An important area of investigation concerns defining the
      regulation of expression of such receptor/ligand pairs, since understanding such
      events are central in the quest to manipulate immune responses. Receptors for the
      neuropeptide, substance P, are present on a variety of leukocytes, and these
      receptor positive cells respond to in vitro stimulation with substance P in a
      variety of ways. Unfortunately, little is known about the regulation of
      expression of substance P or its receptor in leukocytes. Here we begin to address
      this question by examining the ability of macrophages to express mRNAs which
      encode substance P and its receptor. A radiolabeled oligonucleotide probe
      complementary to the mRNA which encodes substance P (i.e., preprotachykinin mRNA)
      hybridized to a 1.3 kb RNA species present in rat macrophages. In addition, the
      expression of this RNA could be upregulated 6 to 8 fold when macrophages were
      stimulated with LPS. The ability of macrophages to synthesize and secrete
      immunoreactive-substance P was demonstrated by incorporation of L-[35S]methionine
      into material from macrophage cultures which could be recognized by a monoclonal
      antisubstance antibody. Macrophage RNA of approximately 3.1 kb in size was
      capable of hybridizing with an oligonucleotide probe complementary to rat brain
      substance P receptors. In addition, this RNA could be upregulated when cells were
      exposed to LPS. Taken together, these studies suggest that the genes used by
      neuronal cells and macrophages to encode substance P and its receptor are similar
      if not identical.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380280
TI  - Quantitative determination of mdr1 gene expression in leukaemic cells from
      patients with acute leukaemia.
AB  - By using a quantitative RNA-RNA solution hybridisation method, the average number
      of mdr1 RNA transcripts per cell was measured in total nucleic acid extracts of
      leukaemic cells from patients with acute leukaemia. The results in different
      types of leukaemia were (number of patients with detectable mdr1 RNA/total number
      of patients; median number of transcripts per cell in samples with detectable
      mdr1 RNA); de novo untreated acute myelocytic leukaemia (AML): 20/44; 0.7,
      secondary acute myelocytic leukaemia: 8/13; 1.1, acute lymphocytic (ALL) and
      undifferentiated leukaemia: 5/14; 0.6, relapsed leukaemia: 7/15; 0.7. Forty-six
      patients with de novo untreated acute leukaemia (AML: n = 34, ALL: n = 12) were
      evaluable for response to induction chemotherapy. Twelve of 18 patients (67%)
      with detectable mdr1 RNA levels achieved complete remission compared to 23 of 28
      (82%) with undetectable levels (P = 0.40). The remission duration tended to be
      longer among patients with undetectable mdr1 RNA (P = 0.08). Leukaemic cells were
      analysed on consecutive occasions in 12 patients. The level of expression
      increased in four and decreased in two. In conclusion, expression of mdr1 RNA is
      common in acute untreated leukaemia. However, treatment with cytostatic drugs
      seems only rarely to increase the proportion of leukaemic cells that express mdr1
      RNA. Expression of the mdr1 gene could be one of several equally important
      factors contributing to drug resistance in acute leukaemia.

PMID- 1380281
TI  - Expression of basic fibroblast growth factor, FGFR1 and FGFR2 in normal and
      malignant human breast, and comparison with other normal tissues.
AB  - The expression of basic fibroblast growth factor (bFGF) and two of its receptors,
      FGFR1 and FGFR2, was detected using the polymerase chain reaction, and quantified
      by comparison to the relative amount of product obtained following co
      amplification of the ubiquitous glyceraldehyde phosphate dehydrogenase
      transcript. Varying levels were found in the vast majority of both cancer and non
      malignant breast biopsies as well as in samples of several other normal human
      tissues. Significantly less bFGF was present in cancers (P less than 0.0001).
      Similarly, FGFR2 product was also much less in cancer tissues (P = 0.0078), as
      was FGFR1 (P = 0.002). FGFR1 levels in cancers tended to be higher in those which
      were oestrogen receptor positive (P less than 0.06). Amplification of different
      coding regions showed evidence of variant forms of FGFR1 RNA. Cancers appeared to
      have a significantly greater proportion of PCR product corresponding to the
      region between the third immunoglobulin like domain and the tyrosine kinase
      domain (P = 0.046). Differential expression was observed in breast cell lines,
      with bFGF in the normal derived HBL100, HBR SV1.6.1 and 184A1 but little or none
      in ZR-75-1, MCF-7, T47D and MDA-MB-231. FGFR1 was present in most of these but
      FGFR2 was absent from T47D, MDA-MB-231 and HBL100. ZR-75-1 cells had a marked
      preponderance of FGFR1 variants lacking part of the coding sequence. Aberrant
      receptor processing may provide clues concerning the role of FGF's and their
      potential involvement in malignancy.

PMID- 1380282
TI  - Suramin prevents neovascularisation and tumour growth through blocking of basic
      fibroblast growth factor activity.
AB  - Inhibition of angiogenesis through blocking of growth factors involved in this
      process could be a novel therapeutic approach in several important pathologies,
      neoplasia among them. Suramin has recently been described to possess
      antineoplastic activity in animals and humans, and it has been proposed that an
      important role in this activity is played by antagonism of growth factors and
      especially bFGF. To investigate this hypothesis in vivo, we used gelatin sponges
      loaded with bFGF and implanted subcutaneously in mice. Suramin showed an
      inhibitory activity on bFGF-induced angiogenesis, whereas it was inactive in the
      case of heparin-complexed bFGF. Suramin was also studied in an in vivo model of
      tumour-induced angiogenesis using the murine M5076 reticulosarcoma, a tumour
      producing significant levels of bFGF. Suramin was able to reduce tumour growth
      and tumour induced angiogenesis, and exogenous administration of bFGF countered
      suramin effects.

PMID- 1380283
TI  - Prognostic factors in juvenile chronic granulocytic leukaemia.
AB  - A retrospective analysis of the clinical and haematological characteristics of
      patients diagnosed as having juvenile chronic granulocytic leukaemia between 1971
      and 1986 was carried out. Thirty-three children were identified who were between
      the ages of 18 weeks and 8.8 years at diagnosis. The disease was more frequent in
      boys than girls (23:10). The most common presenting symptoms were skin rash (58%)
      and bleeding manifestations (45%). All patients had some degree of splenomegaly
      and in 88% this was more than 3 centimetres below the costal margin. Hepatomegaly
      and lymphadenopathy were also frequent findings. Anaemia was common and
      leucocytosis an invariable finding with a white cell count above 50 x 10(9) 1-1
      in 42%. Monocytosis was found in 78%. Haemoglobin F measurements were available
      in 31 children and above 10% in 22 (67%). No child had the Philadelphia
      chromosome or monosomy 7. Thirty children were treated with chemotherapy, with a
      variable degree of symptomatic improvement. Twenty-nine patients had died with a
      median survival time of 5 months. The commonest cause of death was complications
      of bone marrow failure and no child developed acute leukaemia. Presenting
      characteristics associated with a longer survival period were age less than 6
      months (P = 0.02), female sex (P = 0.02), HbF less than 10% (P = 0.0004) and the
      absence of bleeding manifestations (P = 0.03). We conclude that the prognosis for
      children aged over 6 months, with a raised HbF level is very poor, and that, in
      the absence of possible bone marrow transplantation, consideration should be
      given to novel treatment approaches for these patients.

PMID- 1380284
TI  - Phylogeny of rapidly growing members of the genus Mycobacterium.
AB  - The 16S rRNAs from nine rapidly growing Mycobacterium species were partially
      sequenced by using the dideoxynucleotide-terminated, primer extension method with
      cDNA generated by reverse transcriptase. The sequences were aligned with 47 16S
      rRNA or DNA sequences that represented 30 previously described and 5 undescribed
      species of the genus Mycobacterium, and a dendrogram was constructed by using
      equally weighted distance values. Our results confirmed the phylogenetic
      separation of the rapidly and slowly growing mycobacteria and showed that the
      majority of the slowly growing members of the genus represent the most recently
      evolved organisms. The 24 strains which represented 21 rapidly growing species
      constituted several sublines, which were defined by the following taxa: (i)
      Mycobacterium neoaurum and M. diernhoferi, (ii) M. gadium, (iii) the M. chubuense
      cluster, (iv) the M. fortuitum cluster, (v) M. kommossense, (vi) M. sphagni,
      (vii) M. fallax and M. chitae, (viii) M. aurum and M. vaccae, (ix) the M.
      flavescens cluster, and (x) M. chelonae subsp. abscessus. Our phylogenetic
      analysis confirmed the validity of the phenotypically defined species mentioned
      above, but our conclusions disagree with most of the conclusions about
      intrageneric relationships derived from numerical phenetic analyses.

PMID- 1380285
TI  - Delineation of Borrelia burgdorferi sensu stricto, Borrelia garinii sp. nov., and
      group VS461 associated with Lyme borreliosis.
AB  - We studied 48 Borrelia isolates that were associated with Lyme borreliosis or
      were isolated from ticks and identified three DNA relatedness groups by using the
      S1 nuclease method. The three DNA groups (genospecies) were associated with
      specific rRNA gene restriction patterns, protein electrophoresis patterns, and
      patterns of reactivity with murine monoclonal antibodies. Genospecies I
      corresponded to Borrelia burgdorferi sensu stricto since it contained the type
      strain of this species (strain ATCC 35210); this genospecies included 28 isolates
      from Europe and the United States. Genospecies II was named Borrelia garinii sp.
      nov. and included 13 isolates from Europe and Japan. Genospecies III (group
      VS461) included seven isolates from Europe and Japan.

PMID- 1380286
TI  - rRNA gene restriction patterns as taxonomic tools for the genus Aeromonas.
AB  - In the genus Aeromonas there are at least 13 DNA hybridization groups, which are
      difficult to differentiate biochemically. We investigated the usefulness of rRNA
      gene restriction patterns for characterization and identification of the various
      groups. Genomic DNA was digested with restriction endonuclease SmaI, transferred
      to a nylon membrane, and hybridized with biotinylated plasmid pKK3535 containing
      the rrnB operon of Escherichia coli. The SmaI bands at 0.8 to 4 kb but not those
      at positions corresponding to sizes larger than 4 kb showed a good correlation
      with hybridization groups, allowing identification of strains to the level of
      genetic species. We demonstrated that the 567-bp fragment localized between
      positions 80 and 647 of the 16S ribosomal gene of E. coli was essential for
      hybridization to the low-molecular-weight fragments, whereas the remainder of the
      operon did not hybridize to these fragments. On the basis of these results, we
      concluded that the Aeromonas chromosome contains multiple rRNA operons which may
      be used for species identification.

PMID- 1380287
TI  - Desulfovibrio longus sp. nov., a sulfate-reducing bacterium isolated from an oil
      producing well.
AB  - A novel type of sulfate-reducing bacteria with unusual morphology was isolated
      from an oil-producing well in the Paris Basin. The cells of this bacterium,
      strain SEBR 2582T (T = type strain), are long, thin, flexible rods, contain
      desulfoviridin, and are physiologically similar to members of the genus
      Desulfovibrio. On the basis of 16S rRNA sequence data, this strain should be
      included in the genus Desulfovibrio. However, strain SEBR 2582T differs from
      other members of this genus morphologically, physiologically, and
      phylogenetically. Thus, a new species, Desulfovibrio longus sp. nov., is proposed
      for this organism.

PMID- 1380288
TI  - DNA relatedness among some thermophilic members of the genus Methanobacterium:
      emendation of the species Methanobacterium thermoautotrophicum and rejection of
      Methanobacterium thermoformicicum as a synonym of Methanobacterium
      thermoautotrophicum.
AB  - DNA reassociation was used to determine levels of relatedness among four
      thermophilic Methanobacterium strains that are able to use formate and between
      these organisms and two representative strains of Methanobacterium
      thermoautotrophicum, strain delta HT (= DSM 1053T = ATCC 29096T) (T = type
      strain) and strain Marburg (= DSM 2133). Three homology groups were delineated,
      and these groups coincided with the clusters identified by antigenic
      fingerprinting. The first group, which had levels of cross hybridization that
      ranged from 73 to 99%, included M. thermoautotrophicum delta HT, Methanobacterium
      thermoformicicum Z-245, Methanobacterium sp. strain THF, and Methanobacterium sp.
      strain FTF. The second and third groups were each represented by only one strain,
      Methanobacterium sp. strain CB-12 and M. thermoautotrophicum Marburg,
      respectively (cross-hybridization levels, 13 to 30 and 29 to 33%, respectively).
      Our results indicate that the name M. thermoformicicum should be rejected as it
      is a synonym of M. thermoautotrophicum. The taxonomic positions of strains
      Marburg and CB-12 need further investigation.

PMID- 1380289
TI  - Phylogenetic interrelationships of members of the genera Aeromonas and
      Plesiomonas as determined by 16S ribosomal DNA sequencing: lack of congruence
      with results of DNA-DNA hybridizations.
AB  - The phylogenetic interrelationships of members of the genera Aeromonas and
      Plesiomonas were investigated by using small-subunit ribosomal DNA (rDNA)
      sequencing. Members of the genus Aeromonas formed a distinct line within the
      gamma subclass of the Proteobacteria. Plesiomonas shigelloides also clustered
      within the confines of the gamma subclass of the Proteobacteria but exhibited a
      closer association with members of the family Enterobacteriaceae than with
      members of the family Aeromonadaceae. Species of the genus Aeromonas exhibited
      very high levels of overall sequence similarity (ca. 98 to 100%) with each other.
      Several of the relationships derived from an analysis of the rDNA sequence data
      were in marked disagreement with the results of chromosomal DNA-DNA pairing
      experiments. Diagnostic rDNA signatures that have possible value for
      differentiating most Aeromonas species were discerned.

PMID- 1380290
TI  - Bacillus methanolicus sp. nov., a new species of thermotolerant, methanol
      utilizing, endospore-forming bacteria.
AB  - The generic position of 14 strains of gram-positive bacteria able to use methanol
      as a growth substrate was determined. All are obligately aerobic, thermotolerant
      organisms that are able to grow at temperatures of 35 to 60 degrees C. Nine of
      the strains produce oval spores at a subterminal-to-central position in slightly
      swollen rod-shaped cells. DNA-DNA hybridization studies, 5S rRNA sequence
      analysis, and physiological characteristics revealed that all 14 strains cluster
      as a well-defined group and form a distinct new genospecies. Analysis of the 16S
      and 5S rRNA sequences indicated that this new species is distinct from Bacillus
      brevis but closely related to B. firmus and B. azotoformans. The name proposed
      for this new species is B. methanolicus. The type strain, PB1, has been deposited
      in the National Collection of Industrial and Marine Bacteria as NCIMB 13113.

PMID- 1380291
TI  - Characterization of three thermophilic strains of Methanothrix ("Methanosaeta")
      thermophila sp. nov. and rejection of Methanothrix ("Methanosaeta")
      thermoacetophila.
AB  - Three thermophilic Methanothrix ("Methanosaeta") strains, strains PTT (= DSM
      6194T) (T = type strain), CALS-1 (= DSM 3870), and Z-517 (= DSM 4774), were
      characterized chemotaxonomically and compared with five mesophilic strains,
      Methanothrix soehngenii ("Methanosaeta concilii") GP6 (= DSM 3671), Opfikon (=
      DSM 2139), FE (= DSM 3013), UA, and PM. These methanogens were exclusively
      acetotrophic and had a characteristic sheathed structure. The DNA base
      compositions of the strains which we studied ranged from 50.3 to 54.3 mol%
      guanine plus cytosine. The thermophilic strains often had phase-refractive gas
      vesicles inside their cells. Denaturing electrophoresis of proteins showed that
      the mesophilic and thermophilic Methanothrix strains formed two distinct groups
      and that there were differences in protein patterns between the groups. The
      difference between the thermophiles and mesophiles was also verified by comparing
      partial 16S rRNA sequences (ca. 30 base differences in ca. 540 bases). On the
      basis of our results, we propose the name Methanothrix thermophila for the three
      thermophilic strains. The type strain of M. thermophila is strain PT (= DSM
      6194). We also propose that the name Methanothrix thermoacetophila ("Methanosaeta
      thermoacetophila"), which was given to strain Z-517 (type strain), should be
      rejected because of its description, which was based on an enrichment culture,
      was inadequate.

PMID- 1380292
TI  - Phylogenetic position of Cowdria ruminantium (Rickettsiales) determined by
      analysis of amplified 16S ribosomal DNA sequences.
AB  - The 16S ribosomal DNA sequence of Cowdria ruminantium, the causative agent of
      heartwater disease in ruminants, was determined. An analysis of this sequence
      showed that C. ruminantium forms a tight phylogenetic cluster with the canine
      pathogen Ehrlichia canis and the human pathogen Ehrlichia chaffeensis. Although a
      close relationship between the genus Cowdria and several members of the tribe
      Ehrlichieae has been suspected previously, the tight phylogenetic cluster with E.
      canis and E. chaffeensis is surprising in view of known differences in host
      preference and target cells.

PMID- 1380293
TI  - [For child-friendly treatment in pediatric hospitals. Pediatric-surgical
      treatment and pediatric nursing in pediatric hospitals].

PMID- 1380294
TI  - Comparison of the solophenyl-red polarization method and the immunohistochemical
      analysis for collagen type III.
AB  - In the present study, we have compared the staining pattern of the Solophenyl-Red
      3 BL-method for the visualization of collagen type III with the
      immunohistochemical staining in serial sections from 7 skin wounds (wound age 3
      days up to 4 weeks) to elucidate the specificity of the histochemical staining
      method. Large amounts of collagen type III were clearly detectable in the
      investigated wounds using the immunohistochemical technique. In the sections
      stained with Solophenyl-Red, however, only 3 out of 7 skin lesions showed a
      significant positive red staining at the wound margin or in the granulation
      tissue, while the adjacent normal connective tissue revealed a typical intensive
      staining. Using polarization microscopy no characteristic bright green fibrils,
      as reported for collagen type III, could be seen in the wound areas without
      positive Solophenyl-Red staining. Since the localization of collagen type III
      detected by immunohistochemistry and the presumed distribution of this collagen
      type by the Solophenyl-Red method was not identical, the histochemical
      polarization method has to be regarded as non-specific for visualization of this
      collagen type.

PMID- 1380295
TI  - Angiostatic activity and metabolism of cortisol in the chorioallantoic membrane
      (CAM) of the chick embryo.
AB  - There is considerable interest in the discovery of compounds which inhibit
      angiogenesis dependent (neovascular) diseases. The chick embryo, due to the rapid
      development of an extensive vascular capillary network in the chorioallantoic
      membrane (CAM), has been used extensively as a model for studying angiogenesis.
      Angiostatic steroids are a new class of compounds which inhibit the growth of new
      capillaries in the chick CAM and in other models of neovascularization. Despite
      the potential therapeutic importance of these compounds, little is known about
      the ability of the CAM to metabolize these steroids. We have evaluated the
      ability of the chick CAM to metabolize cortisol which is both an angiostatic
      steroid as well as a glucocorticoid. When CAM homogenate was incubated with
      [3H]cortisol and NADPH at 37 degrees C and pH 7.4, and the reaction products
      analyzed by reverse phase HPLC, [3H]cortisol was converted exclusively to 20 beta
      dihydrocortisol (4-pregnen-11 beta,17 alpha,20 beta,21-tetrol-3-one). The
      cortisol metabolite, 20 beta-dihydrocortisol, has very little glucocorticoid
      activity, but shows significant angiostatic activity in the CAM comparable to
      cortisol. The apparent Km determined for cortisol metabolism was 12 microM and
      the observed Vmax was 1.4 mumol cortisol/mg protein/min. The majority of the 20
      beta-reductase activity was found in the soluble (242,000 g) fraction of CAM
      homogenate. 20 beta-Reductase activity in chick embryo CAM has not been
      previously reported.

PMID- 1380296
TI  - Increased levels of interferon regulatory element-binding activities in nuclei of
      high interferon-producing If-1h mice.
AB  - The transient induction of type I interferon (IFN) genes following a viral
      infection involves transcriptional derepression and activation, mediated by
      positive and negative factors which bind to upstream cis-acting elements. We have
      transfected the human IFN-beta gene into primary splenocytes from mice regulated
      by the If-1 locus and have shown that the exogenous gene is regulated by this
      locus in a manner similar to that of endogenous IFN genes. Using nuclear extracts
      from splenocytes of C57BL/6 (If-1h) and BALB/c (If-1l) mice in gel retardation
      assays, we found that levels of DNA-binding activities for the interferon
      regulatory element and its subelements were constitutive in nuclear extracts of
      spleen cells. Levels of DNA binding to the interferon regulatory element were
      higher in extracts from the nuclei of If-1h mice and thus correlate with the
      higher levels of human IFN-beta mRNA detected in these transfected cells and the
      transcription of the endogenous IFN genes. Higher levels of DNA
      binding/transcription factors found in nuclei from spleen cells of If-1h mice may
      be involved in the expression of the If-1 phenotype.

PMID- 1380297
TI  - Effects of granulocyte colony-stimulating factor, interleukin-1 alpha, and
      interleukin-6 on prolonged myelosuppression induced by nimustine hydrochloride in
      rats.
AB  - The myelorestorative effects of granulocyte colony-stimulating factor (G-CSF),
      interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6) were studied in F-344
      rats which had been treated with cyclophosphamide (CY), carboplatin (CBDCA), or
      nimustine hydrochloride (ACNU). In CY- or CBDCA-pretreated rats, significantly
      higher peripheral white blood cell (WBC) count was observed in animals treated
      with G-CSF and IL-1 alpha, while the platelet (PLT) count was elevated by IL-6
      treatment. All of the cytokines had little effect on the hemoglobin (HB) value.
      Animals treated with ACNU had prolonged myelosuppression. Treatment of these
      animals with G-CSF and IL-1 alpha significantly enhanced the recovery of HB value
      as well as WBC count. Higher PLT counts were observed in treated groups, but a
      statistical difference was not evident. Combination therapy with G-CSF and IL-1
      alpha, G-CSF and IL-6, or IL-1 alpha and IL-6 did not have any significant
      beneficial effects on the peripheral blood cell count in ACNU-pretreated rats
      over single agent therapy. Conversely, the combination of IL-6 and G-CSF had an
      unfavorable effect on HB and PLT levels. In rats which received multiple doses of
      ACNU, G-CSF treatment exhibited a beneficial effect on WBC, HB, and PLT levels,
      the most prominent on the HB value. These findings suggest that treatment with
      hematopoietic cytokines may be most beneficial when combined with anticancer
      drugs which are known to cause prolonged myelosuppression.

PMID- 1380298
TI  - Effect of benzodiazepine ligands on Ca2+ channel currents in Xenopus oocytes
      injected with rat heart RNA.
AB  - Voltage-dependent Ca2+ channel (VDCC) currents have been measured in Xenopus
      oocytes injected with heart RNA purified from 7 day old rats, using voltage clamp
      technique. The currents were evoked by depolarizing voltage steps, using Ba2+ as
      charge carrier. Electrophysiological analysis of the current revealed two
      components: a slow, L-type, dihydropyridine (DHP)-sensitive current and a
      transient, DHP-insensitive, current. The benzodiazepine (BZ) ligands diazepam and
      Ro5-4864 decreased the current with micromolar affinity, with potency order of
      Ro5-4864 greater than diazepam greater than clonazepam. The central antagonist
      Ro15-1788 did not interfere with the effect of these drugs, thus excluding the
      possible involvement of the "central type" receptor. The slow current that was
      increased about 3 fold in the presence of 0.5 microM Bay K 8644, was less
      potentiated when previously treated with Ro5-4864 or diazepam. Current-voltage
      relation of the peak inward current and the steady state activation curve showed
      a small shift towards negative potentials in the presence of 50 microM diazepam.
      It is concluded that the benzodiazepine ligands block DHP-sensitive voltage
      dependent Ca2+ channels with a very marginal effect on the transient, DHP
      insensitive current. Also it is emphasized that Xenopus oocytes can serve as a
      useful model system to study the pharmacology of these important drugs on cardiac
      Ca2+ channels.

PMID- 1380299
TI  - Protein kinase C stimulates dense tubular Ca2+ uptake in the intact human
      platelet by increasing the Vm of the Ca(2+)-ATPase pump: stimulation by phorbol
      ester, inhibition by calphostin C.
AB  - The effects of protein kinase C (PKC) on Ca2+ transport were investigated in
      human intact platelets. The indicator quin2 was used to measure the free
      cytoplasmic Ca2+ concentration ([Ca2+]cyt) and to search for possible PKC effects
      on the Ca(2+)-ATPase extrusion pump located in the plasma membrane. The Ca2+
      indicator chlorotetracycline (CTC) was used to study PKC effects on the dense
      tubular Ca(2+)-ATPase uptake pump. The activity of PKC was stimulated by phorbol
      12-myristate 13-acetate (PMA) and was inhibited with calphostin C. Neither PKC
      activation nor inhibition had any effect on [Ca2+]cyt or the Ca2+ extrusion pump.
      Substantial activation of the dense tubular pump was observed with PMA. In
      resting platelets bathed in 2 mM external Ca2+ giving [Ca2+]cyt = 102-106 nM,
      activation of PKC by PMA (100 nM) increases the rate and extent of dense tubular
      Ca2+ uptake to 1.62 +/- 0.35 and 1.25 +/- 0.3 times control value (respectively).
      The Vm of the dense tubular pump was measured by using ionomycin to manipulate
      [Ca2+]cyt. It is shown that PMA increases the Vm by a factor of 1.7 +/- 0.4 but
      has no effect on the Km value (= 180 nM). An unexpected finding was that PKC
      activity supports a portion of the basal activity of the dense tubular Ca2+ pump
      in resting platelets. Preincubation with the inhibitor calphostin C (100 nM)
      decreases the rate and extent of dense tubular Ca2+ uptake in resting platelets
      by 38 +/- 5% and 29 +/- 21% (respectively). This is due to a 28 +/- 9% decrease
      in the Vm of the dense tubular pump. This suggests that there is a low level of
      stimulation of dense tubular Ca2+ pump mediated by PKC in resting platelets.

PMID- 1380300
TI  - The role of anion channels in the mechanism of acrosome reaction in bull
      spermatozoa.
AB  - The involvement of anion channels in the mechanism of the acrosome reaction (AR)
      was investigated. The AR was induced by Ca2+ or by addition of the Ca2+ ionophore
      A23187. The occurrence of AR was determined by following the release of acrosin
      from the cells. In order to investigate the role of anion channels in the AR,
      several anion-channel inhibitors were tested, mainly DIDS (4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid). Other blockers, like SITS (4
      acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid), furosemide, probenecid
      and pyridoxal 5-phosphate, were also tested. We found that DIDS binds covalently
      to sperm plasma membrane in a time- and concentration-dependent manner. Maximal
      binding occurs after 2 h with 0.3 mM DIDS. DIDS and SITS inhibit AR in a
      concentration-dependent manner. The IC50 of DIDS and SITS in the presence of
      A23187 is 0.15 and 0.22 mM, respectively. Tributyltin chloride (TBTC), an Cl-/OH-
      exchanger, partially overcomes DIDS inhibition of the AR. HCO3- is required for a
      maximal acrosin release and Ca(2+)-uptake, in the presence or absence of A23187.
      It is known that HCO3- activates adenylate cyclase and therefore, increases the
      intracellular level of cAMP. The inhibition of the AR by DIDS decreases from 95
      to 50% when (dibutyryl cyclic AMP (dbcAMP) was added, i.e., HCO3- is no longer
      required while elevating the level of cAMP in an alternative way. Moreover, we
      show that the stimulatory effect of HCO3- on Ca(2+)-uptake is completely
      inhibited by DIDS. We conclude that DIDS inhibits AR by blocking anion channels,
      including those that transport HCO3- into the cell.

PMID- 1380301
TI  - Sterol specific inactivation of gramicidin A induced membrane cation
      permeability.
AB  - Channel inactivation, a time-dependent decrease of the high-cationic permeability
      induced by gramicidin A, has been found both in cholesterol containing red blood
      cell membranes and lipid bilayers (Schagina et al., (1989) Biochim. Biophys. Acta
      978, 145-150). The rate of channel inactivation strongly depends on the
      phospholipid to cholesterol molar ratio of the membrane. The channel inactivation
      is suggested to be the result of an interaction between gramicidin and
      cholesterol in a stoichiometry of 1:5. Cholesterol dependent inactivation is
      shown also for gramicidin A analogs: tryptophan-N-formylated gramicidin A, o
      pyromellitilgramicidin and malonylbisdesformylgramicidin. When cholesterol in the
      membrane is substituted by sitosterol, the inactivation of gramicidin-induced
      cation permeability is preserved, while in the presence of either ergosterol or 7
      dehydrocholesterol no indication of the channel inactivation is observed. Thus,
      the structure of the 'B', ring, not the apolar tail of the sterol molecule,
      appears to be important in the inactivation process.

PMID- 1380302
TI  - Proteolytic modification of raw-starch-digesting amylase from Bacillus circulans
      F-2 with subtilisin: separation of the substrate-hydrolytic domain and the raw
      substrate-adsorbable domain.
AB  - Raw starch-digesting amylase (BF-2A, 93,000 Da) from Bacillus circulans F-2 was
      converted into two components during digestion with subtilisin. The two
      components were separated and designated BF-2A' (63 kDa) and BF-2B (30 kDa),
      respectively. BF-2A' exhibited the same hydrolysis curve for soluble starch as
      the original amylase (BF-2A). Moreover, the catalytic activities of original and
      modified enzymes were indistinguishable in Km, Vmax and in their specific
      activity for soluble starch hydrolysis. However, its absorbability and
      digestibility on raw starch was greatly decreased. Furthermore, the enzymatic
      action pattern on soluble starch was differed greatly from that of BF-2A. The
      stability of the enzymes decreased below pH 5.5 and at 50 degrees C, while it was
      quite stable even at pH 12. On the other hand, the smaller peptide (BF-2B) could
      be adsorbed onto raw starch. From these results, it is suggested that the larger
      peptide (BF-2A') has a region responsible for the expression of the enzyme
      activity to hydrolyze soluble substrate, and the smaller peptide (BF-2B) plays a
      role on raw starch adsorption and also contributes to the original enzyme-to
      enzyme stabilization. A proposed model of the raw-starch-digesting enzyme from
      this strain is extensively discussed.

PMID- 1380303
TI  - Interaction of catalytic-site mutants of Bacillus subtilis alpha-amylase with
      substrates and acarbose.
AB  - The interactions of the three catalytic-site mutants of Bacillus subtilis alpha
      amylase/(DN176 [Asp-176----Asn], EQ208 [Glu-208----Gln] and DN269 [Asp-269---
      Asn]) with substrates and a pseudo-oligosaccharide inhibitor, acarbose, have been
      studied by means of difference absorption spectroscopy and affinity
      chromatography. The addition of maltopentaose or soluble starch to the inactive
      mutant enzymes mostly resulted in difference spectra characteristic of tryptophan
      perturbation, enabling determination of the dissociation constants. The results
      show that conversion of Glu-208 to Gln greatly enhanced substrate binding,
      implying that Glu-208 interacts unfavorably with the substrate's ground state,
      preventing its optimal fit to the active site. The affinity for acarbose was
      greatly reduced in DN269 and EQ208, but less so in DN176, suggesting that Asp-269
      and Glu-208 are more important than Asp-176 in stabilizing the transition state.
      These results are consistent with Glu-208 and Asp-269 being the key catalytic
      residues, as proposed for Taka-amylase A.

PMID- 1380304
TI  - Endothelin increases [Ca2+]i in rat pancreatic acinar cells by intracellular
      release but fails to increase amylase secretion.
AB  - In individual fura-2 loaded cells of rat pancreatic acini endothelin-1 (ET-1) (10
      50 nM) induced sustained oscillations in [Ca2+]i. At higher concentrations a
      larger, but transient increase in [Ca2+]i was observed, which was largely
      unaffected by removal of extracellular Ca2+. ET-1 induced the release of Ca2+i
      from the same store as cholecystokinin (CCK), but with less potency. At
      concentrations of endothelin which transiently increased Ca2+, ET-1 increased the
      accumulation of inositol phosphates. Specific binding sites for 125I-endothelin
      were demonstrated on rat pancreatic acini. A single class of binding sites was
      identified with an apparent Kd 108 +/- 12 pM and Bmax of 171 +/- 17 fmol/mg for
      ET-1. The relative potency order for displacing [125I]ET was ET-1 greater than ET
      2 greater than ET-3. In contrast to CCK and the non-phorbol ester tumour promoter
      Thapsigargin (TG) which induce both transient and sustained components of [Ca2+]i
      elevation, ET-1 failed to increase amylase release over the range 100 pM-1
      microM.

PMID- 1380305
TI  - Signal mechanisms in the activation of basophils and mast cells.
AB  - While several important biochemical steps have been observed to occur in
      basophils and mast cells, there remain some very important links to be
      established. Notably, it is important to understand the exact role of the IgE
      receptor and the need for its aggregation. The description of the GTP-binding
      protein involved in IgE-mediated signal transduction is necessary, as is a
      description of the proteins involved in calcium movement. Control mechanisms
      remain unclear, and the length of the signal transduction pathway has yet to be
      defined. Much of the data points to multiple requisite pathways, and yet only
      calcium elevations have a relatively well-demonstrated pro-degranulatory role.
      Until some of these events are understood in detail, the means by which cell
      sensitivity is regulated may remain a mystery. Finally, it will be important to
      determine if mast cells and basophils use distinctive IgE-mediated signal
      transduction pathways.

PMID- 1380306
TI  - Interferon activation of eosinophils.

PMID- 1380307
TI  - Cytokine stimulation of human basophil histamine release.

PMID- 1380308
TI  - Hemopoietic growth factors regulate basophil function and viability.
AB  - Table 1 summarizes the activities of hemopoietins on immature and mature
      basophils. IL-3, GM-CSF, and IL-5 enhanced basophil histamine release and in
      vitro survival, while G-CSF, M-CSF, and IL-4 had no enhancing activities at all.
      In addition, IL-3 and GM-CSF induced basophil chemotaxis. Although IL-3 was
      proved to have proliferative and differentiation-inducing activities on basophils
      in vitro and in vivo, the other two factors (GM-CSF and IL-5), which are also
      capable of regulating basophil functions and viability, might potentially
      participate in proliferation or differentiation of human basophils, but this
      hypothesis remains without sure foundation. Studies on the roles of both factors
      in human basophilopoiesis need extension. The fact that IL-3, GM-CSF, and IL-5
      regulate basophil function and viability in vitro demonstrates possible
      mechanisms for the regulation of basophil function and viability in IgE-mediated
      reactions (especially in late-phase reactions) in vivo by these factors. Since
      these factors could be produced by antigen-stimulated T-cells or epithelial cells
      through the inflammatory process, these factors could participate in exacerbation
      and prolongation of hypersensitivity reactions by inducing the migration and
      enhancing functions and the lifespan of basophils.

PMID- 1380309
TI  - Effects of cytokines on the expression of adhesion molecules in allergic
      diseases.

PMID- 1380310
TI  - Granulocyte colony-stimulating factors as therapeutic agents.

PMID- 1380311
TI  - G-CSF and M-CSF: preclinical and clinical results.

PMID- 1380312
TI  - Clinical trials of granulocyte colony-stimulating factors for treatment of bone
      marrow depression associated with cancer chemotherapy.

PMID- 1380313
TI  - AIDS and palliative care.

PMID- 1380314
TI  - Augmented secretion of lysosomal enzyme into pancreatic juice after short term
      obstruction of the pancreatic duct in rats.
AB  - To find out if and when lysosomal enzymes are excreted into pancreatic juice in
      physiological and pathological conditions, the changes in the secretion of
      cathepsin B into pancreatic juice were investigated in 66 Wistar rats with
      cannulation of common pancreatic-biliary duct and common bile duct, and infusions
      of caerulein and secretin. In a separate experiment ducts were cannulated and
      secretin infused as before, but in one group the ducts were "obstructed" and in
      another they were allowed to remain patent. Obstruction of the pancreatic duct
      for three hours caused a moderate significant rise in serum amylase activity.
      Cathepsin B activity in the pancreatic subcellular fractions was redistributed,
      and the amount of cathepsin B increased. In rats with obstructed ducts the
      secretion of cathepsin B and other lysosomal enzymes that were stimulated by
      caerulein was significantly greater than in the animals in which the ducts
      remained patent. Lysosomal enzymes associated with zymogen granules are secreted
      into pancreatic juice together with digestive enzymes after stimulation by gut
      hormones, and they may have pathophysiological roles in pancreatic juice.

PMID- 1380315
TI  - Techniques for clearing ovules for studies of megagametophyte and early
      postfertilization development in Rhododendron.
AB  - Using ovule clearing, more than 33,600 ovules of Rhododendron nuttallii T. W.
      Booth (Ericaceae) were examined for megagametophyte and early postfertilization
      stages at daily intervals from anthesis until 3 weeks after pollination.
      Pretreatments with amyloglucosidase to digest integumentary and gametophyte
      starch and Stockwell's bleach to remove tannins from the integumentary epidermis
      were necessary. Ovules were cleared by a combination or modifications of Herr's
      four-and-a-half or Stelly's hemalum-methyl salicylate techniques and were
      observed using differential interference contrast optics. The method proved
      suitable for large-scale quantitative studies of ovule development and
      fertilization. A general protocol is suggested as a starting point for ovule
      clearing studies.

PMID- 1380316
TI  - A mixture of paraphenylenediamine and imidazole: its effect on the extraction of
      lipid droplets during electron microscopy staining.
AB  - To prevent extraction of lipids during a double staining procedure for electron
      microscopy, the tissue slices, double fixed with glutaraldehyde and osmium
      tetroxide to preserve microvesicular lipid droplets in the cytoplasm, were
      immersed for 2 hr in veronal buffer (pH 9.0) containing 0.5% p-phenylenediamine
      and 0.5% imidazole immediately after postfixation. The stained sections of the
      immersed tissue slice showed blackened, well circumscribed lipid droplets similar
      to those in corresponding unstained sections. Moreover, highly contrasting
      features of the cellular architecture could be visualized with the double
      stained, as well as routinely prepared sections.

PMID- 1380317
TI  - An update on protein stains: amido black, coomassie blue G, and coomassie blue R.
AB  - Samples of amido black, Coomassie blue G, and Coomassie blue R obtained over a
      number of years were tested for dye content, impurities, and effectiveness for
      staining proteins after polyacrylamide gel electrophoresis and for protein dye
      binding assays. Some impurities produced reactions resembling metachromasia with
      specific proteins, although instances of true metachromatic staining are also
      reported. Several simple assays are given for determining dye content and
      relative levels of impurities. Recommendations are made for selecting batches of
      commercial dyes which are most likely to perform satisfactorily.

PMID- 1380318
TI  - A comparison of substrates for human umbilical vein endothelial cell culture.
AB  - We have studied culture conditions which facilitate the growth of stable, non
      proliferating, human umbilical vein endothelial cell (HUVEC) monolayers. Gelatin
      and fibronectin coatings, with or without glutaraldehyde cross-linking, on both
      plastic and glass were investigated for initial attachment of HUVEC and growth
      characteristics. The presence during culture of intercellular (IC) junctions
      demonstrated by silver staining, expression of platelet endothelial cell adhesion
      molecule-1 (PECAM-1) and maintenance of a cobblestone appearance of HUVEC
      monolayers were assessed over time. Glutaraldehyde cross-linked fibronectin and
      gelatin coatings on glass and glutaraldehyde cross-linked gelatin or untreated
      fibronectin coatings on plastic served as good substrates for short term culture.
      Long term (20 days) cultures of HUVEC which maintained silver and PECAM-1
      staining of IC junctions and a cobblestone appearance could be achieved if
      glutaraldehyde cross-linked gelatin coatings on glass were used as substrates.

PMID- 1380319
TI  - Epitope mapping by photobleaching fluorescence resonance energy transfer
      measurements using a laser scanning microscope system.
AB  - The donor photobleaching method (T. M. Jovin and D. J. Arndt-Jovin. 1989. Annu.
      Rev. Biophys. Biophys. Chem. 18:271-308.) has been adapted to an ACAS 570 (laser
      scanning microscope) system to measure fluorescence resonance energy transfer
      (FRET) on individual human peripheral blood T cells. Photobleaching was completed
      in approximately 100 ms in our case and it followed double-exponential kinetics.
      The energy transfer efficiency (E) was approximately 20% between the CD4 epitopes
      OKT4-FITC and Leu-3a-PE as well as between OKT4E-FITC and OKT4-PE. E was
      approximately 8% between OKT4-FITC and Leu-4-PE (alpha CD3) and barely detectable
      (approximately 4%) from OKT4-FITC to Leu-5b-PE (alpha CD2). The E values obtained
      by the photobleaching method were highly reproducible both in repeated
      measurement of identical samples and in experiments with different batches of
      cells and were in agreement with the flow cytometric donor quenching
      measurements. As expected, E measured between primary and secondary layers of
      antibodies increased (from approximately 14% to approximately 28%) when F(ab')2
      fragments were substituted for whole antibody molecules as the donor. On a T cell
      line we mapped the distance between the idiotypic determinant of the T cell
      receptor (TcR) and the Leu-4 epitope of CD3 as proximal as E = 28%, as compared
      to E = 4% between a framework TcR epitope and Leu-4. In the latter case, however,
      approximately 40% less Leu-4 was bound suggesting that the antigen binding site
      of TcR is in close proximity with one of the two CD3 epsilon chains, which hence
      are not equivalent.

PMID- 1380320
TI  - Constant helical pitch of the gramicidin channel in phospholipid bilayers.
AB  - X-ray diffraction has been applied in measuring the helical pitch of the
      gramicidin channel in oriented bilayers of dilauroylphosphatidylcholine (DLPC)
      and dimyristoylphosphatidylcholine (DMPC) at a polypeptide concentration of 9.1
      mol %. The diffraction data show the helical pitch of gramicidin to be 4.7 +/-
      0.2 A in both gel and liquid-crystalline phase bilayers, with and without
      monovalent cations. In addition, the width of the reflection due to the pitch of
      the helical gramicidin channel is consistent with a five turn helix.

PMID- 1380321
TI  - Models for gramicidin channels.

PMID- 1380322
TI  - Free-radical mechanisms involved in the formation of sequence-dependent
      bistranded DNA lesions by the antitumor antibiotics bleomycin, neocarzinostatin,
      and calicheamicin.

PMID- 1380323
TI  - The beginning of the Liege School of Comparative Physiology.

PMID- 1380324
TI  - Evidence that endothelium-dependent relaxation to histamine in the rat common
      carotid artery is mediated by EDRF.
AB  - The mechanism of histamine-induced relaxation in the isolated rat common carotid
      artery was analysed. Histamine (3 x 10(-7)-10(-4) mol/l) caused a concentration
      dependent relaxation of the artery. Indomethacin, a cyclo-oxygenase inhibitor,
      and diethylcarbamazine, a lipoxygenase inhibitor, did not affect the relaxant
      response of the artery to histamine. After removal of the vascular endothelium
      the histamine-induced relaxation was strongly reduced. Moreover, hemoglobin and
      methylene blue, inhibitors of endothelium-derived relaxing factor (EDRF),
      prevented or reversed the relaxant effect of histamine. These findings confirm
      that the histamine-induced relaxation is to a greater extent endothelium
      dependent. It is concluded that the endothelium-dependent component in the
      relaxant response of the rat common carotid artery to histamine results from the
      release of EDRF.

PMID- 1380325
TI  - Phosphoamino acid phosphatases in normal and cancerous tissues of the human
      uterus, cervix and ovary.
AB  - The activities of phosphoamino acid phosphatases were measured in human
      myometrium and fibroma and normal and cancerous tissues of the cervix and ovary.
      Phosphoserine and phosphothreonine phosphatases were detected only in myometrium
      and fibroma and the values were relatively low. Phosphotyrosine phosphatase
      activities in myometrium and fibroma fell within a similar range; this was also
      the case for ovary and ovarian carcinoma, whereas values for cervical tumours
      were significantly higher than for normal cervix. Activities of phosphotyrosine
      phosphatase in serum from patients with cervical or other tumours were, in most
      cases, within the range of values obtained for normal serum.

PMID- 1380326
TI  - [Heart volume overload in the rabbit during growth via chronic arteriovenous
      fistula. Evaluation of an original model].
AB  - A heart volume overload model was developed in male New Zealand rabbit nine weeks
      old, using femorofemoral or jugulo-carotid fistulae, producing 50% increase of
      the mean cardiac output. An evaluation was performed after 2 and 11 weeks. It was
      evaluated by dimensional echocardiogram and doppler system flow measurement at
      the aorta ring, angiography and right cardiac pressure recording. This
      hemodynamic analysis was completed by a heart and fistulae histopathological
      study. In some volume overload cases, an increasing volume index parameter was
      described. Two weeks later an increase of the cardiac frequency and a dilatation
      of the aorta ring were observed but the stroke volume remained unchanged. 11 old
      weeks fistula animals presented similar frequency and stroke volume. So, the
      heart compensatory mechanisms varied with the age of the rabbit. The right
      catheter and cardiac angiography were not useful for ventricular volume overload
      estimation. Histopathological study showed parenchymal changes and alveolo
      capillary congestion. An increase of the heart weight/body weight ratio was
      described. When analysed by ultrasound and blood flow measurement, data were
      similar to those obtained by invasive pressure recordings or by dilution system.
      An experimental model of overload volume in rabbit with non invasive recording
      methods (bidimensional ultrasound and doppler system) can be proposed.

PMID- 1380327
TI  - Characterization of chick serum lipoproteins isolated by density gradient
      ultracentrifugation.
AB  - Serum lipoproteins from 12h fasted male chicks (15-day-old) were separated into
      20 fractions by isopycnic density gradient ultracentrifugation. A new procedure
      was described by collecting the different fractions from the bottom of tube
      instead of by aspiration from the meniscus of each tube. Analyses of chemical
      composition of serum lipoproteins have permitted to reevaluate the density limits
      of major classes: VHDL, d greater than 1.132 g/ml; HDL, d 1.132-1.084 g/ml; LDL,
      d 1.084-1.038; IDL, d 1.038-1.022; and VLDL d less than 1.022. HDL fractions
      clearly predominated (approx. 77% of total lipoproteins) while IDL and VLDL were
      present at low percentage. LDL was the fraction richest in cholesterol;
      triacylglycerol content clearly increased from HDL to VLDL, while protein content
      decreased. All the chemical components of chick serum lipoproteins were
      accumulated in HDL, although triacylglycerol was relatively distributed in all
      the lipoprotein classes.

PMID- 1380328
TI  - Bound and purified alkaline phosphatase from rat duodenal and jejunal brush
      border membranes: kinetics and magnesium stimulation.
AB  - Brush-border membranes from rat duodenal and jejunal mucosa were prepared by
      differential Ca(2+)-precipitation. Kinetical properties and Mg(2+)-stimulation of
      alkaline phosphatase were studied for the enzyme either bound to these membranes
      or purified from these membranes by liquid chromatography. With p
      nitrophenylphosphate as substrate, the alkaline phosphatase apparent Km was lower
      in jejunum (90 microM) as compared with duodenum (160 microM), and lower for the
      purified enzyme (jejunum: 55 microM; duodenum: 97 microM) as compared to the
      bound one. In the presence of 5 mM MgCl2, the substrate affinity was in all cases
      decreased. For the bound enzyme Vmax was 10 times greater in duodenum compared to
      jejunum. 5 mM MgCl2 tripled the Vmax of the duodenal bound enzyme and increased
      it by 50% for the jejunal one, but a seven-fold increase was recorded for the
      purified enzyme at both levels of intestine. The apparent affinity for Mg2+ was
      similar for the bound and the free enzyme, for duodenum and for jejunum (Mg0.5:
      +/- 40 microM).

PMID- 1380329
TI  - The digestive and metabolic utilization of the dietary protein: effect of
      clenbuterol and protein level.
AB  - The influence of a beta-agonist, clenbuterol, added to the diet at 0, 30 and 50
      mg/Kg was studied on the digestive and metabolic use of the dietary protein in
      Wistar rats of two different weights (70 and 200 g). The rats had been fed diets
      containing different protein levels (4, 10 and 15%). Treatment with clenbuterol
      did not have any effects on the absorption of the dietary protein in any of the
      studies released. The beta-agonist did not alter fecal nitrogen excretion nor did
      it change the digestion coefficient of the protein at the doses used. Clenbuterol
      significantly increased (P less than 0.01) urinary nitrogen excretion in younger
      animals fed diets containing low levels of protein (4%). On the other hand, in
      animals of greater age/weight that had been fed diets with a sufficient protein
      content (15%), the beta-agonist significantly reduced urinary nitrogen excretion
      (P less than 0.001). From the results of this study, it can be concluded that in
      order that clenbuterol can significantly increase nitrogen balance and protein
      retention, the animals must be given a sufficient exogenous protein intake and
      they must not be at a stage of maximum growth potential.

PMID- 1380330
TI  - Are the unusual morphological and physiological features of the leatherback
      turtle (Dermochelys coriacea) paralleled at the molecular level? A study on A4
      (muscle-type) isozyme of its lactate dehydrogenase.
AB  - A4 (muscle-type) Lactate Dehydrogenase was purified to homogeneity from
      Dermochelys coriacea. The steady-state kinetic features of the enzyme show
      remarkable similarities with those displayed by many other heterothermal LDH's
      from cold-blooded vertebrates.

PMID- 1380332
TI  - [Involvement of 3-dehydroecdysteroids in the ecdysone biosynthetic pathway in
      Locusta migratoria, in vitro].
AB  - Prothoracic glands of the locus, Locusta migratoria, incubated in vitro converted
      tritiated 3-dehydrocetodiol (22,23,24,25 3H4-14 alpha-hydroxy-5 beta-cholest-7-en
      3,6-dione) into ecdysteroids and 3-dehydroecdysteroids as far as the final
      products of the two series, ecdysone and 3-dehydroecdysone. In the two series,
      the different compounds are formed in the same quantities, except for 2,22-desoxy
      products, the nature of which could not have been determined. Converted 3
      dehydroecdysone issued from 3-dehydrocetodiol is transformed into ecdysone after
      several hours incubation with Locusta last instar larvae hemolymph. Till now is
      has been impossible to determine if the reduction of 3-dehydroecdysteroids took
      place into the prothoracic glands or in the incubation medium. In no case is 3
      dehydrocetodiol converted into cetodiol. Conversion rates of the different
      compounds, either issued from cetodiol or from 3-dehydrocetodiol as precursors,
      are of same importance, so that a weak specificity of the hydroxylation enzymes
      must be considered.

PMID- 1380331
TI  - Biochemical changes in progressive muscular dystrophy, XVI. Effect of glutamic
      acid, aspartic acid and glycine on the amino acid content of skeletal muscle of
      dystrophic mice.
AB  - The effect of exogenous administration of glutamic acid (GL), aspartic acid (A)
      and glycine (G) on individual amino acids in the free amino acid pool was studied
      in skeletal muscles of 60- to 70-day-old normal (N) and dystrophic (D) mice. Both
      N and D mice received either 0.25 ml of saline (S) or 250 mg/kg weight of GL, A
      or G in 0.25 ml S subcutaneously for 13 days. GL, A, G or S did not cause any
      significant changes in the body and skeletal muscle weights of either group. Most
      of the individual amino acids were increased in skeletal muscles of GL-treated
      mice and were decreased in A- or G-treated animals compared to S administration
      in the N group. The picture was more dramatic in the D group: GL-induced amino
      acid elevations were more pronounced than the values of N- or S-treated D
      controls. A and G elicited amino acid increases in D mice compared to their S
      treated counterparts. Most of the individual amino acids in skeletal of the D
      group were decreased relative to N mice after S, GL or A administration. This was
      evident when the D/N ratio was calculated for S, GL and A. The situation was very
      different after G administration since of the individual amino acids were
      augmented in the skeletal muscle of D mice compared to N animals.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380333
TI  - An arginine regulated gamma-guanidobutyrate ureahydrolase from tench liver (Tinca
      tinca L.).
AB  - A gamma-guanidobutyrate ureahydrolase isolated from tench liver has been
      characterized. Some of its physicochemical properties like pH effect and thermal
      stability resemble those of arginases, however it shows some peculiarities that
      makes it different from arginases and other amidino hydrolases. Thus cation
      requirement is not as strong as in arginases, and the Km value for gamma-guanido
      butyric acid (230 +/- 25 mM) is shifted to a lower value (45 +/- 5 mM) by 5 mM
      arginine. The possible regulatory role of arginine on gamma-guanidobutyrate
      ureahydrolase activity is discussed.

PMID- 1380335
TI  - Effect of diet on folates levels and distribution in selected tissues of the rat.
AB  - A technique for the extraction, purification and concentration of folates,
      followed by high performance liquid chromatography assay with fluorometric
      detection of the three principal derivatives (tetrahydrofolic, 5-methyl
      tetrahydrofolic and formyl-tetrahydrofolic acids) has been applied to the
      determination of tissue folates in rats. The levels found are compared to those
      of the microbiological assay using Lactobacillus casei. When rats were fed a diet
      containing 1 mg of folic acid per kg of food, levels in the intestinal mucosae,
      liver, whole blood and brain were 0.59, 14.87, 0.28 and 0.83 nmol/g of tissue. An
      exogenous supply of 200 mg of folic acid/kg of food significantly increased
      folate levels in all tissues studied, except for the brain: 1.51, 28.93, 0.52 and
      0.99 nmol/g, respectively in the above four tissues. The separation of the
      various derivatives and a variable supply of folic acid have enabled the
      conversions of these metabolites to be studied.

PMID- 1380334
TI  - Inhibition of the cholinergic twitch response in guinea-pig common bile duct: an
      evaluation of the effects of noradrenaline, clonidine and fentanyl.
AB  - Presynaptic inhibitory effects of noradrenaline, clonidine and fentanyl on twitch
      contractions evoked by transmural electrical stimulation were investigated in
      guinea-pig common bile duct (CBD). Antagonism of the response to fentanyl by
      naloxone and to noradrenaline and clonidine by yohimbine confirmed the
      involvement of presynaptic opiate and alpha 2-adrenoceptors respectively.
      Clonidine caused desensitization of presynaptic alpha 2-adrenoceptors. No cross
      desensitization between clonidine and fentanyl was observed. Furthermore, partial
      agonistic activity of clonidine at presynaptic alpha 2-adrenoceptors was also
      observed by the antagonism of noradrenaline response in this preparation.

PMID- 1380336
TI  - Modification of electrophysiological properties of rat heart with age.
AB  - The authors have determined the serum thyroid hormone levels [total (TT3) and
      free (FT3) triiodothyronine], the heart weight/body weight ratio and the heart
      rate of differently aged male rats. The variations of these parameters show a
      modification of thyroid state as a function of ageing. The authors have also
      recorded, at about 26 degrees C, resting and action potentials from single cells
      of papillary muscles isolated from the same groups of rats. The animals in the
      higher thyroid state exhibited a repolarization speed higher than the other
      animals. The thyroidectomy, performed on 50 day old rats, and T3 treatment of the
      thyroidectomized rats give rise to modifications of repolarization speed and then
      of action potential duration analogous to ones obtained in previous study for
      animals thyroidectomized at 30 days of age. These data demonstrate that the
      modifications of heart electrophysiological properties with age, are due
      fundamentally to thyroid state modifications. The results suggest also that the
      cardiac chronotropism modifications which the rat undergoes as a function of
      ageing are due to the changes of levels of thyroid hormone which might exert its
      effect by modifying the ion channel kinetics as well as the cardiac receptors.

PMID- 1380337
TI  - A new method for the measurement of tremor at rest.
AB  - This paper establishes a standard method for measuring human tremor. The
      electronic instrument described is an application of this method. It solves the
      need for an effective and simple tremor-measuring instrument fit for wide
      distribution. This instrument consists of a piezoelectric accelerometer connected
      to an electronic circuit and to an LCD display. The signal is also analysed by a
      computer after accelerometer analogic/digital conversion in order to test the
      method. The tremor of 1079 healthy subjects was studied. Spectral analysis showed
      frequency peaks between 5.85 and 8.80 Hz. Chronic cigarette-smoking and coffee
      drinking did not modify the tremor as compared with controls. Relaxation session
      decreased tremor significantly in healthy subjects (P less than 0.01). This new
      tremor-measuring method opens new horizons in the understanding of physiological
      and pathological tremor, stress, anxiety and in the means to avoid or compensate
      them.

PMID- 1380338
TI  - Prophenoloxidase activation in the hemolymph of American cockroach, Periplanata
      americana.
AB  - Prophenoloxidase has been successfully extracted in a stable condition from the
      Hemocytes of Periplaneta americana using cane sugar saline solution. Other media
      used to extract prophenoloxidase were found not suitable. Among the activators
      used (trypsin, chymotrypsin, sodium oleate and SDS), trypsin activated the
      proenzyme maximum. Activation during electrophoresis resulted in the dissociation
      of proenzyme in to two sub-units. The enzyme has also been localised by the
      agarose gel electrophoresis. The proenzyme was stable up to 50 degrees C and
      precipitated at 60 degrees C and above. The activated enzyme showed maximum
      activity at pH 7.0. Preliminary attempt has also been made to precipitate the
      enzyme protein against the antibody raised in rabbit.

PMID- 1380339
TI  - Circadian rhythms in glutathione and glutathione-S transferase activity of rat
      liver.
AB  - The experiments were conducted to examine the existence of circadian rhythms in
      glutathione concentration and glutathione S-transferase activity in the liver of
      the rat. In animals synchronized to a 12:12 h light-dark cycle and fasted at 6
      different time points to allow exactly 24 h of fasting, both, glutathione
      concentration and glutathione S-transferase activity show diurnal variation with
      a maximum during the light period and a minimum at night. On the other hand the
      hepatic protein level was maximal during the light period and decreased to its
      lowest level during the dark period. The implications of such oscillations in the
      circadian rhythms of toxicological or therapeutical effects of many xenobiotic
      agents are clear.

PMID- 1380340
TI  - Bleeding stress and metabolic changes in the crab Scylla tranquebarica
      (Fabricius).
AB  - In the crab scylla tranquebarica, bleeding stress is characterized by changes in
      proteins, lactic acid and water content of muscles, hepatopancreas and
      haemolymph. Proteins seemed to be involved in energy expenditure and internal
      osmotic balance. Lactate levels increased, suggesting a shift in aerobic
      metabolism. Water content fell.

PMID- 1380341
TI  - In vitro electro-mechanical activity of the human colon. Simultaneous recording
      of the electrical patterns of the two muscle layers.
AB  - Electrical and mechanical activity on longitudinal and circular layers of the
      human sigmoid colon were simultaneously studied. Recordings were obtained from
      two electrode sites spaced 3 cm apart in a piece of colon which had been resected
      surgically and perfused in an organ bath. Spontaneous electrical activity of the
      colon showed slow waves and spikes. Slow waves were present for only 24.5% and
      12% of the recording time on the longitudinal and circular layers, respectively,
      and they appeared as localized activity which was irregular in amplitude and
      varying in frequency. Electrical coupling between the two muscle layers was
      rarely seen and slow waves were not associated with pressure changes. Spiking
      activity were recorded as short and long spike bursts on both muscle layers.
      Short spike bursts were localized activity superimposed on slow waves. The
      associated mechanical activity, which consisted of single weak pressure changes
      or prolonged contractions with summation, was determined by slow wave frequency.
      Long spike bursts were seen at irregular intervals and were either propagated or
      not propagated activity associated with electrical oscillations ranging from 24
      to 46 cpm. Mechanical activity consisted of sustained tonic contractions
      propagated or not propagated in the same way as the electrical pattern.
      Coordinated electrical activity of the two muscle layers seldom occurred when
      spontaneous activity was being recorded. Electrical activity on both muscle
      layers was very sensitive to stretching and could be initiated or modulated by
      pharmacological agents. In particular, our findings showed that stimulation
      induced coordinated spiking activity on the two muscle layers and caused
      mechanical activity, propagated orally or aborally, which consisted of long
      lasting, high amplitude contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380342
TI  - Management of non-Hodgkin's lymphoma.
AB  - This brief review of non-Hodgkin's lymphomas emphasizes aspects of clinical
      research which have led to important improvements in the management of patients,
      and examines research questions with relevance for the future. In the
      intermediate- and high-grade lymphomas, strategies to intensify drug regimens
      have proved successful in raising rates of curative outcome. With the
      introduction of growth factors and peripheral stem cell transfusion to support
      nadir cytopenias it becomes possible to further develop dose-intense regimens.
      Identification and selection of poor prognostic subsets is key to the further
      application of these approaches, since the therapeutic ratio may be narrow and up
      to 50% of patients may be cured with less toxic regimens. In the low-grade
      lymphomas where a curative outcome is less certain, the application of intensive
      therapy has proved more controversial and results remain preliminary.
      Nevertheless, durable remissions appear achievable in advanced-stage CR patients
      utilizing low-dose consolidative irradiation or autologous transplantation. In
      contrast to intermediate- and high-grade lymphomas where intensive therapy is
      often reserved for responding poor-risk presentations, in low-grade lymphoma
      intensive therapy and consolidation is most successfully applied to good-risk
      patients.

PMID- 1380343
TI  - Direct chemical ionization mass spectrometry of short-chain polysaccharides.
AB  - Underivatized short-chain polysaccharides such as two inulins from different
      plants containing up to 35-40 monosaccharide units with molecular weights of up
      to 6500 Da and dextran T 1.5 containing up to 16-20 monosaccharide units with
      molecular weights of up to 3200 Da have been investigated by direct chemical
      ionization. Under soft ionization conditions such as ammonia chemical ionization
      and reduced ion-source temperature, it was possible to obtain spectra of the
      native polysaccharides showing dominant ion series corresponding to ammonia
      adduct ions of oligosaccharides, and also ion series corresponding to ammonia
      adduct ions of anhydro-oligosaccharides.

PMID- 1380345
TI  - Chromaffinity, uranaffinity and argentaffinity of small granule-containing (SGC)
      cells in rat superior cervical ganglia.
AB  - A systemic examination on the small granule-containing (SGC) cells in rat
      superior cervical ganglia was conducted by conventional and cytochemical electron
      microscopy including chromaffin, argentaffin and uranaffin reactions. According
      to the fine structure of dense cored vesicles (DCVs) in the cytoplasm, three
      types of small granule-containing (SGC) cells were revealed--Type I: 90-160 nm
      vesicles with cores of moderate or low electron density; Type II: 130-330 nm
      vesicles, polymorphic with highly electron dense cores; Type III: elongated
      vesicles (170 nm x 60 nm) with cores of moderate to low electron density. The
      majority of SGC cells were the Type I cells (78%) and Type II and III cells made
      up 13% and 9% of SGC cell population, respectively. Cytochemical results
      demonstrated that only the Type II cells displayed a positive chromaffin reaction
      and all three types of SGC cells showed argentaffinity and uranaffinity. The
      present study is the first to demonstrate the argentaffin reaction at
      ultrastructural level in SGC cells of sympathetic ganglia. Based on the results
      of the present study we also concluded that (1) the DCVs of Type II SGC cells
      contained noradrenaline and (2) biogenic amines and nucleotides (ATPs) coexisted
      in the DCVs of all three types of SGC cells.

PMID- 1380344
TI  - N,N dimethylglycine and L-carnitine as performance enhancers in athletes.

PMID- 1380346
TI  - Organochlorine residues in human adipose tissue of the population of Zaragoza
      (Spain).

PMID- 1380347
TI  - Aliphatic and aromatic hydrocarbons in indoor air.

PMID- 1380348
TI  - Distribution of sub-slab injected Dursban TC (chlorpyrifos) in a loamy sand soil
      when used for subterranean termite control.

PMID- 1380349
TI  - Toxicity of selected insecticides to the penaeid prawn, Metapenaeus monoceros
      (Fabricius).

PMID- 1380350
TI  - Impact of corn canopy on foliar distribution of chlorpyrifos (Lorsban) when
      applied via a center pivot irrigation system.

PMID- 1380351
TI  - Dermal levels of methyl-parathion, organochlorine pesticides, and
      acetylcholinesterase among formulators.

PMID- 1380352
TI  - Residue levels of organochlorines and mercury in cattle egret, bubulcus ibis,
      eggs from the Faiyum Oasis, Egypt.

PMID- 1380354
TI  - Survival rate of patients with glomerulonephritis.
AB  - This is a fourteen-year follow-up study of patients with primary and secondary
      glomerulonephritis, diagnosed by percutaneous renal biopsy. The survival curves
      of 271 patients were determined, applying the method described by Cutler 1958.
      The term "kidney death" was used for the patients who had died or developed end
      stage renal failure. The five-year survival rates were: 32 for diffuse
      proliferative glomerulonephritis (chronic), 22 for focal glomerulosclerosis, 30
      for membranoproliferative glomerulonephritis, 62 for membranous nephropathy, 90
      for focal and mesangioproliferative glomerulonephritis, and 94 for IgA
      nephropathy. Two diseases of the secondary glomerulonephritis group were
      analyzed: renal amyloidosis with a survival rate of 8 and lupus nephritis 51.

PMID- 1380353
TI  - Persistence of some pesticides in the aquatic environment.

PMID- 1380355
TI  - Phagocytic function in patients with recurrent urinary tract infections.
AB  - Phagocytes play an essential role in the host's defence against uropathogenic
      bacteria which are mostly extracellular pathogens. The functional capacity of
      peripheral blood phagocytes (predominantly polymorphonuclears, PMN) was
      investigated in 47 patients (urethrocystitis, acute or chronic pyelonephritis)
      and in healthy persons. The random mobility of phagocytes was determined by
      measuring their spontaneous migration from a capillary tube. Using radioactively
      labelled sheep erythrocytes as targets and the phagocytes as effector cells,
      ingestion, digestion and extracellular cytotoxicity were determined. All the four
      phagocytic functions in patients were significantly lower than in healthy
      controls, especially in patients with chronic pyelonephritis. These results link
      reduced phagocytosis by blood phagocytes with recurrent urinary tract infections
      (UTI). Whether the defect is primary or secondary to infection (and only
      transient) should be the object of further studies.

PMID- 1380356
TI  - Electrocardiographic and clinical anticipation of the left ventricular systolic
      function, systemic vascular resistance, and myocardial hypertrophy--normal values
      and validation of method in patients with arterial hypertension.
AB  - In order to study the hemodynamic effects of the antihypertensive drugs in
      patients with essential hypertension, systolic time intervals from ECG data were
      extrapolated. The study was performed in 36 healthy individuals and 38 patients
      with essential hypertension without a drug therapy and/or in the wash out period
      more than three weeks and after a treatment. The stroke volume (SV) was
      determined as a product of the ejection time (ET), the pulse pressure (PP) and
      the flow coefficient (Kf). The Kf was extrapolated from Doppler-cardiographic
      parameters and it significantly correlated with the normal diastolic blood
      pressure (TA(d)) if the QT is not prolonged and the electrical systole/mechanical
      systole ratio (QS2/MS) not disturbed: Kf = 9.356 e-0.008 TA(d); r = -0.9. In
      arterial hypertension the correlation was also curvilinear: kf = 3.962 e-0.001
      TA(d); r = -0.99. The arteriolar stiffness was defined as the PP/SV ratio. The
      cardiac output (CO) and systemic vascular resistance (SVR) were determined
      according to conventional formulas by known clinical and extrapolated ECG data.
      The cardiac contractile or muscle performance was defined as corrected changes of
      the ejection function for the given afterload according to the formula: I (-0.004
      TA(d) + PEP/ET) -0.014 x 100; the normal 95% confidence limits for the laboratory
      used are -6.6% to +6%. Systolic time intervals were extrapolated from ECG data in
      the consecutive manner: QS2 = kQS2 x QT, ET = kET x JT, and MS = kMS x ET. The
      correlation of kQS2 with QT is curvilinear: kQS2 = 2.760 e-2.732 QT.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380357
TI  - Partial laryngectomy in transglottic carcinoma.
AB  - At the ENT Department of Zagreb University from 1973 to 1982 119 cases of
      transglottic carcinoma were treated. In the first group of 20 cases total
      laryngectomy was done. Five years later, ten of the patients treated had
      survived. Primary and secondary neck metastases were present in 6 cases, i.e.
      30%. In the second group of 99 cases partial laryngectomy (vertical and combined)
      was done. Five years later 70 cases had survived, i.e. 70%. Primary and secondary
      neck metastases were present in 19 cases, i.e. 19%. In the partial laryngectomy
      the reconstruction was done by fascia sternohyoidea and partial resection of the
      cricoid and totally of the arythenoid in the cases where there was the
      indication. Postoperative irradiation was given in cases with neck metastases and
      where resection margin was inadequate.

PMID- 1380358
TI  - Mentally ill offenders and their medical treatment according to the criminal law
      of Croatia.
AB  - The authors have analyzed psychopathological and criminal characteristics of the
      75 patients, regarding the census on 31. 12. 1985. Group 1 (N = 55) was committed
      by court for inpatient treatment and group 2 (N = 20) was committed by court for
      outpatient treatment. The analysis was based on the data in psychiatric
      expertises and medical files containing the relevant facts for the study. 46
      patients (92%) in the first group are diagnosed as psychotic disturbances,
      regarding the ICD-9, while in the second group there were 15 patients (75%) of
      the same diagnostic category. The other patients were diagnosed as mentally ill
      (including the mentally retarded, epileptic etc. patients). The age distribution
      shows that a majority of the patients of the first group are between 31-50 years
      (73%) and for the second group the rate is 50%. According to the criminal acts
      the first group mainly consists of patients who had committed one murder or more
      (36 + 3), while in the second group the patients offended against property and
      committed body violations (8 + 6). The average institutional treatment, which is
      not legally limited, is over 10 years, and for outpatient treatment group it is
      13 months, legally limited up to 2 years. The main criterion for psychiatric and
      legal distribution of the patients into two groups is the estimation of their
      social danger. The given data prove that the estimation of the social danger is
      mainly defined by the psychopathological characteristics of the subjects and the
      type of the criminal act they committed, while the other parameters are less
      influential for the estimation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380359
TI  - Serum gastrin concentration in chronic renal failure.
AB  - On the basis of the existing experimental and clinical studies about the factors
      affecting the appearance of hypergastrinemia in renal failure, it can be
      concluded that the kidney plays an important, but not the only, role in the
      degradation of endogenous gastrin in humans. In this process the key role is
      played by the blood flow through the kidney, the preservation of the peritubular
      capillary system, and the functional kidney mass. Glomerular filtration has no
      particular importance in the extraction of gastrin from the circulation, while
      through the urine only a small amount of gastrin is excreted. In the
      decomposition of a part or at least some molecular gastrin forms, an important
      role is played by the capillary systems of extra-renal tissue. One further
      conclusion is that hypergastrinemia in patients with renal failure is the result
      of the combined effects of the reduced catabolism of gastrin in the kidney and
      its increased synthesis which is for the most part connected with hypochlohydria
      and secondary hyperparathyroidism. In patients with renal failure there exists
      the inhibition of the gastrin acid secretion which is the cause of the weakening
      of the mechanism of the feedback connection between HCl and gastrin, while
      because of a permanent stimulation of G-cells, the hyperplasia of these cells
      develops, as well as the increased secretory activity, and hypergastrinemia.
      Parietal cells become less sensitive to a permanently increased serum gastrin
      concentration but still capable of reacting to the maximal stimulus. In patients
      with renal failure, especially those with extreme hypergastrinemia, there
      develops the increased concentration of large, mainly biologically inactive (big
      big gastrin, component I) molecular forms of gastrin.

PMID- 1380360
TI  - Stereological analysis of the female breast alveolar ductulus epithelial cells in
      premenopause and postmenopause.
AB  - Stereological characteristics of the ductular parenchyma epithelial cells were
      analysed ultrastructurally in 18 cases of normal breast tissue. Different
      physiological states were compared in the premenopause and postmenopause. The
      volume density (VV), surface density (SV) and specific surface density (SV/VV) of
      nuclei and the epithelial cell cytoplasm were stereologically examined and
      compared. After a menopause a slight decrease of the volume density (VVj),
      surface density (SVj) and specific surface density (SVj/VVj) of epithelial cell
      nuclei was noted, while the volume density (VVc), surface density (SVc) and the
      specific surface density (SVc/VVc) of the epithelial cell cytoplasm were slightly
      increased.

PMID- 1380361
TI  - Risks of retrobulbar application of anesthetics and drugs.
AB  - In spite of hundreds of harmless retrobulbar applications of anesthetics and
      drugs, a certain risk still exists. In the past ten years in our Department with
      7200 retrobulbar procedures performed in local anesthesia and 12500 retrobulbar
      applications of the drugs (corticosteroids, antibiotics, vasodilatators) 14
      incidents were registered. Palpebral chemosis and retrobulbar hematoma or eyeball
      protrusion were transient in 11 patients. Acute disturbance of the chorioretinal
      circulation occurred in three patients. In one of them vascular occlusion was
      total with permanent loss of vision, while in the other two recuperation of
      vision was the sign that vascular spasm was transient.

PMID- 1380362
TI  - Cor triatriatum dextrum.
AB  - Cor triatriatum dextrum was an incidental echocardiographic finding in a 5 year
      old boy and a 9 year old girl, who were evaluated for the presence of a heart
      murmur. Apart from slightly enlarged right atria, they had otherwise normal
      hearts and were symptomless. Most of the patients reported until then had been
      symptomatic due either to the persistent right sinus venosus valve or to commonly
      associated structural heart anomalies. Therefore, the clinical significance of
      asymptomatic cor triatriatum dextrum remains coniectural, but might lie in the
      possibility of development of arrhythmia, progressively worsening interference
      with the systemic venous return and thrombus formation.

PMID- 1380363
TI  - Prognostic value of some parameters of cellular immunity in breast cancer
      patients.
AB  - In 45 histologically verified breast cancer patients the cell-mediated immune
      responses were tested prior to surgical therapy. The cell immunity was assessed
      by the percentage of T and active T-lymphocytes and by measuring the lymphocyte
      reactivity to phytohemagglutin (PHA) and concanavalin A (Con A). Disease-free
      interval was longer and the mortality after 3, 5 and 8-year follow-up
      significantly lower in the group of patients with the normal number of T and
      active T-lymphocytes than in the group of patients with the lower number of those
      cells. The proliferative response of lymphocytes to Con A and PHA assessed in
      allogeneic and autologous serum also seemed to be a useful prognostic parameter.
      The survival was significantly longer in the group of patients with a normal
      lymphocyte reactivity to those mitogens than in the non-reactive group.

PMID- 1380364
TI  - Influence of phenobarbital and triiodothyronine on the development of hepatic
      eosine transport in rats.
AB  - In male Wistar rats aged 20 and 60 days the influence of a 5-day-treatment with
      phenobarbital (PB, 75 mg/kg b.m. i.p.), triiodothyronine (T3, 100 micrograms/kg
      b.m. s.c.) and both agents simultaneously (PB+T3) on eosine accumulation of liver
      slices in vitro and biliary excretion of eosine in vivo was investigated. PB
      enhanced bile acid independent bile flow. T3 accelerated eosine accumulation in
      liver slices. The combined treatment with PB+T3 had no additional effects. The
      simultaneous action of PB+T3 could not induce the maturation of the rate limiting
      excretion process for organic anions in 20-day-old rats.

PMID- 1380365
TI  - Influence of stepwise uncoupling and temporary anoxia on pancreatic enzyme
      secretion by isolated rat acini.
AB  - For special studies on pancreatic diseases a parameter is needed to record
      alterations of the cellular energy metabolism. In the in vitro model of isolated
      pancreatic acini, we investigated whether or not at standardized cholecystokinin
      stimulation the energy-consuming process of enzyme secretion can be used to
      monitor changes of the energy-supplying capacity. Rat pancreatic acini were
      isolated via collagenase digestion and characterized by basal and stimulated
      release of amylase and trypsin, oxygen uptake under resting and maximally
      uncoupled conditions and by their ability to accumulate actively rhodamine-6G, as
      a measure of the mitochondrial membrane potential. The stimulation of enzyme
      release did not find a measurable reflection in rhodamine-6G accumulation and in
      the respiratory rat. Stepwise uncoupling of oxidative phosphorylation by 2,4
      dinitrophenol (DNP) and temporary anoxia were used to simulate disturbances of
      the pancreatic energy metabolism in vitro. With increasing DNP concentration the
      enzyme release was significantly reduced. While after 30 min anoxia the enzyme
      release still exceeded that of unstimulated control, after 60 min anoxia there
      was no further response to hormonal stimulation. At standardized stimulation and
      after suitable calibration the enzyme release by acini may be used to monitor
      alterations of the pancreatic energy metabolism in vitro.

PMID- 1380366
TI  - Methods in exposure assessment. A summary report of work group I.

PMID- 1380367
TI  - Use of gasoline exposure data and assessment. A summary report of work group III.
AB  - The overall consensus of the Work Group was that the workshop provided an
      excellent opportunity for discussion of the scientific issues pertaining to non
      occupational exposures to gasoline as it related to public health officials,
      legal and regulatory agencies, and industrial (workplace) concerns. It was
      enlightening to discuss the implications of new and existing data and methods for
      determining the public's exposure to gasoline. The workshop resulted in a list of
      data needs and a vision of the future research that will be required to aid
      future users of exposure data.

PMID- 1380368
TI  - Individual and population exposures to gasoline.
AB  - Gasoline is a complex mixture of many constituents in varying proportions. Not
      only does the composition of whole gasoline vary from company to company and
      season to season, but it changes over time. The composition of gasoline vapors is
      dominated by volatile compounds, while "gasoline" in groundwater consists mainly
      of water-soluble constituents. Hydrocarbons, including alkanes, alkenes, and
      aromatics, make up the large majority of gasoline, but other substances, such as
      alcohols, ethers, and additives, may also be present. Given this inability to
      define "gasoline,h' exposures to individual chemicals or groups of chemicals must
      be defined in a meaningful exposure assessment. An estimated 111 million people
      are currently exposed to gasoline constituents in the course of refueling at self
      service gasoline stations. Refueling requires only a few minutes per week,
      accruing to about 100 min per year. During that time, concentrations in air of
      total hydrocarbons typically fall in the range 20-200 parts per million by volume
      (ppmV). Concentrations of the aromatic compounds benzene, toluene, and xylene
      rarely exceed 1 ppmV. Some liquid gasoline is also released, generally as drops
      less than 0.1 g each, but with enough larger spills to raise the average loss per
      gallon dispensed to 0.23 g for stations with conventional nozzles and 0.14 g per
      refueling for stations with vapor recovery nozzles (Stage II controls). Some skin
      exposure may occur from these spills but the exposure has not been quantified.
      Two major types of vehicular emissions have been studied. Evaporative emissions
      include emissions while the vehicle is driven (running losses), emissions after
      the engine has been shut off but is still warm (hot soak), and emissions during
      other standing periods (diurnal) emissions. These evaporative emissions are
      dominated by the more volatile gasoline components. Tailpipe emissions include
      some unreacted gasoline constituents as well as products of combustion (including
      chemicals identical to some of the original constituents of the gasoline) and a
      variety of hydrocarbons and related compounds. Running losses are reported to
      fall in the range of 0.2 to 2.8 g of total hydrocarbons per mile driven, while
      benzene evaporative emissions range from 0.002 to 0.007 g/mile. Benzene levels
      inside travelling vehicles have been reported to average about 13 ppbV in Los
      Angeles. Tailpipe emissions amount to 0.3 to 1.0 g/mile of total hydrocarbons;
      emissions of benzene, polycylic aromatic hydrocarbons, and 1,3-butadiene have
      been reported to range from 0.015 to 0.04 g/mile, 0.00025 to 0.00046 g/mile, and
      0.001 to 0.005 g/mile, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380369
TI  - Exposure to emissions from gasoline within automobile cabins.
AB  - Gasoline is emitted from automobiles as uncombusted fuel and via evaporation.
      Volatile organic compounds (VOC) from gasoline are at higher levels in roadway
      air than in the surrounding ambient atmosphere and penetrate into automobile
      cabins, thereby exposing commuters to higher levels than they would experience in
      other microenvironments. Measurements of VOC concentrations and carbon monoxide
      were made within automobiles during idling, while driving on a suburban route in
      New Jersey, and on a commute to New York City. Concentrations of VOC from
      gasoline were determined to be elevated above the ambient background levels in
      all microenvironments while VOC without a gasoline source were not. The
      variability of VOC concentrations with location within the automobile was
      determined to be smaller than inter-day variability during idling studies. VOC
      and carbon monoxide levels within the automobile cabin differed among the
      different routes examined. The levels were related to traffic density and were
      inversely related to driving speed and wind speed. Overall, daily VOC exposure
      for gasoline-derived compounds during winter commuting in New Jersey was
      estimated to range between 5 and 20% and constituted between 15 and 40% of an
      individual's daily exposure based on comparison to urban and suburban settings,
      respectively. VOC exposure during commuting in Southern California was estimated
      to range between 15 and 60%.

PMID- 1380370
TI  - [A study of infant and child health care "follow up clinic"].
AB  - Health screening examinations of children. The 1st. health screening forms a
      major part of the public health services in community health, but it still
      encounters many problems. In the present study, the health screening programs and
      the infant and child health care follow-up clinic (2nd health screening)
      conducted by the Yoshikawa health center in Saitama-pref., as well as by each
      city and town, were investigated and analyzed. The findings are as follows: 1. In
      the first, health screening they pointed out some developmental disorders of
      21.2%. About 80% of them are "to continue with follow-up observation". And 20%
      are "to go to the hospital and are to have an examination at once". Almost all of
      the above problems are related to psychomotor developmental disorders and
      physical growth delay. 2. The number of the children who made use of public
      expense was only 7 in 1st health screening. 3. The major complaints of the 2nd
      health screening are as follows: 1) speech and language delay 130 (36.4%); 2)
      motor behavior delay 117 (32.8%); 3) physical growth retardation 51 (14.3%); 4)
      emotional disturbances 12 (4.8%). The results of medical diagnosis for 2 years
      (1988-1990) were as follows: 1) speech and language disorders 55 (27.5%); 2)
      mental retardation 29 (14.5); 3) motor disturbances 28 (14.0%). The number of
      children without any problems is 18 (9.0%). 5. After they took the 2nd health
      screening, 138 (38.7%) children consulted with this clinic, and still keep
      consulting. 107 (30.0%) children had a medical examination, and 44 other children
      (12.3%) were introduced to other related facilities. As matters stand, there are
      not enough nurseries or training facilities for borderline children, and high
      risk children. We don't have a complete system for border and high-risk children.
      The facilities for border and high-risk children do not give any specific details
      as to the various special services available. In the future, we forecast that the
      number of children with speech disorders and children with emotional disorders
      including infantile autism will increase, we should analyze the system of border
      and high-risk infants and children in connection with the 2nd health screening
      and discuss how to serve high-risk children effectively.

PMID- 1380371
TI  - Hematopoietic growth factors and human megakaryocyte differentiation.

PMID- 1380372
TI  - Identification of inhibitors of nitric oxide synthase that do not interact with
      the endothelial cell L-arginine transporter.
AB  - The effects of inhibitors of nitric oxide (NO) synthase and other cationic amino
      acids on unidirectional L-arginine transport were studied in porcine aortic
      endothelial cells cultured in microwell plates or perfused in microcarrier
      columns. L-Homoarginine, L-lysine and L-ornithine inhibited transport of L
      arginine. The NO synthase inhibitors NG-monomethyl-L-arginine and NG-iminoethyl-L
      ornithine also reduced L-arginine uptake, whereas NG-nitro-L-arginine and its
      methyl-ester had no inhibitory effect. The ability to modulate selectively
      endothelial cell L-arginine transport or NO synthase activity will allow further
      characterization of the arginine transporter and its role in regulating NO
      biosynthesis.

PMID- 1380373
TI  - Tachykininergic transmission to the circular muscle of the guinea-pig ileum:
      evidence for the involvement of NK2 receptors.
AB  - 1. The effect of newly developed, receptor-selective tachykinin antagonists (GR
      71,251 for NK1 receptors, MEN 10,376 and L 659,877 for NK2 receptors) on
      noncholinergic transmission to the circular muscle of the guinea-pig ileum has
      been investigated. 2. In circular muscle strips of the ileum, electrical field
      stimulation in the presence of atropine (2 microM) and apamin (0.1 microM) evoked
      a complex motor response. The tonic primary contraction in this response was
      reduced by GR 71,251 (10 microM) and MEN 10,376 (3-10 microM) but not by L
      659,877 (up to 10 microM). The presence of apamin was necessary in this
      experimental arrangement to unmask an atropine-resistant primary contraction,
      sensitive to tachykinin antagonists. The motor response was abolished by
      tetrodotoxin. 3. In circular strips of the ileum GR 71,251 (10 microM) inhibited
      the tonic contraction produced by [Sar9] substance P sulphone, a selective NK1
      receptor agonist but not that produced by [beta Ala8] neurokinin A (4-10), a
      selective NK2 receptor agonist. By contrast, MEN 10,376 antagonized the effect of
      the NK2 agonist while leaving the response to the NK1 agonist unaffected. 4. In
      whole segments of the ileum, distension of the gut wall by an intraluminal
      balloon placed at about 1 cm from the point of recording of mechanical activity
      of the circular muscle produced atropine-sensitive phasic contractions (ascending
      enteric reflex). In the presence of atropine (2 microM), a noncholinergic
      response was elicited, which required larger volumes of distension that the
      cholinergic one. The atropine-resistant ascending enteric reflex was enhanced by
      apamin (0.1 microM) and abolished by tetrodotoxin, either in the presence or
      absence of apamin.5. MEN 10,376 (3-lOmicroM) inhibited the atropine-resistant
      ascending enteric reflex in the presence of apamin while GR 71,251 or L 659,877
      (10 microM each) were ineffective. MEN 10,376 inhibited the atropine-resistant
      ascending enteric reflex to a larger extent in the absence than in the presence
      of apamin and also slightly inhibited the ascending enteric reflex in the absence
      of atropine.6. These findings provide evidence for an involvement of NK2
      tachykinin receptors in excitatory transmission to the circular muscle of the
      guinea-pig ileum. NK2 receptors are also involved in the physiological-like
      circular muscle activation produced by stimulation of intramural neuronal
      pathways which subserve the atropine-resistant ascending enteric reflex.

PMID- 1380374
TI  - Characterization of the receptor mediating relaxation to substance P in canine
      middle cerebral artery: no evidence for involvement of substance P in
      neurogenically mediated relaxation.
AB  - 1. The aim of this study was to characterize the neurokinin receptor which
      mediates relaxation of dog isolated middle cerebral artery by the use of
      selective agonists and antagonists and to establish whether substance P is
      involved in the neurogenically mediated relaxant response in this vessel. 2.
      Substance P caused concentration-related, endothelium-dependent relaxations of
      dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha. The
      selective NK1 receptor agonists, GR73632 and substance P methyl ester (SPOMe),
      also caused relaxation with similar maximum effects to those of substance P.
      GR73632 and SPOMe were approximately 20 times and 6 times less potent
      respectively than substance P. The selective NK2 and NK3 receptor agonists,
      GR64349 and senktide, were only weakly active in causing relaxation being at
      least 425 times and 245 times less potent respectively than substance P. 3. The
      selective NK1 receptor antagonist, GR82334, was a potent, specific, competitive
      antagonist of the relaxant effects of substance P. In contrast, the selective NK2
      receptor antagonist, R396 (10 microM) had no effect on the response to substance
      P. 4. Electrical field stimulation of dog isolated middle cerebral artery,
      contracted with prostaglandin F2 alpha, caused neurogenically mediated, non
      adrenergic non-cholinergic (NANC) relaxations. These NANC relaxations were
      unaffected by endothelium removal, GR82334 (10 microM) or by capsaicin (10
      microM) treatment. However, the nitric oxide synthesis inhibitor, L-NG-monomethyl
      arginine methyl ester (L-NMMA) (100 microM) markedly attenuated the response to
      electrical stimulation. 5. These results suggest that substance P causes
      relaxation of dog isolated middle cerebral artery via activation of NK1
      receptors. However, substance P does not appear to be involved in NANC
      neurotransmission. In contrast, the marked inhibitory effect of L-NMMA on NANC
      relaxations implicates nitric oxide in NANC neurotransmission in this vessel.

PMID- 1380375
TI  - Differences in neurokinin receptor pharmacology between rat and guinea-pig
      superior cervical ganglia.
AB  - 1. The depolarizations elicited by seven neurokinin receptor agonists were
      examined in both rat and guinea-pig superior cervical ganglia by use of grease
      gap methodology in the presence of tetrodotoxin (0.1 microM). Responses were
      normalised with respect to 1 microM eledoisin. 2. The rank order of agonist
      potency in the rat ganglia was senktide greater than substance P greater than
      substance P methyl ester = eleidosin = Sar-Met-substance P greater than
      neurokinin B greater than neurokinin A, whereas in guinea-pig superior cervical
      ganglion (SCG) the rank order was senktide greater than Sar-Met-substance P
      greater than neurokinin B = eledoisin = substance P methyl ester. The
      concentration-effect curves for substance P and neurokinin A in guinea-pig
      ganglia were biphasic which precluded the determination of meaningful potency
      values. 3. The maximal depolarization achieved by subtype selective ligands was
      different between these two species. On rat and guinea-pig SCG, the NK3-selective
      ligand, senktide, produced a maximal depolarization of 27% and 274% respectively,
      whereas the NK1-selective ligand, substance P methyl ester, produced
      depolarizations of 77% and 64% respectively. 4. The depolarizations induced by
      substance P methyl ester and senktide in either species were unaffected by
      atropine (1 microM), suggesting a lack of involvement of presynaptic neurokinin
      receptors in the generation of the response. 5. The potency of substance P methyl
      ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the
      peptidase inhibitors bacitracin (40 micrograms ml-1), leupeptin (4 micrograms ml
      1), and chymostatin (2 micrograms ml-1). Similarly, these peptidase inhibitors
      had no effect on the maximal depolarizations achieved by any of these agonists.6.
      It is evident that rat and guinea-pig superior cervical ganglia possess both NK,
      and NK3 receptors, but that their net contribution to depolarizations are
      different between the two species. The depolarizations in guinea-pig SCG are
      mediated predominantly by an NK3 subtype and in rat SCG by an NK, receptor
      subtype.

PMID- 1380376
TI  - Bronchodilatation by tachykinins and capsaicin in the mouse main bronchus.
AB  - 1. The effect of sensory neuropeptides and capsaicin on basal and stimulated tone
      of mouse bronchial smooth muscle has been evaluated. 2. In basal conditions
      neither sensory neuropeptides (substance P, neurokinin A or calcitonin gene
      related peptide (CGRP) nor capsaicin exerted any contractile effects. However,
      when a tonic contraction was induced with carbachol (1 microM) a prompt
      relaxation was induced by substance P (1- 100 nM) and by neurokinin A (1- 100
      nM), with substance P being more potent. A second application of substance P was
      without effect. CGRP (10 nM) produced only a very small and erratic relaxation.
      Relaxation was also induced by capsaicin (1 microM), and this response could be
      evoked only once in each preparation. In 4 out of 6 preparations a cross
      desensitization between substance P and capsaicin was observed. 3. The selective
      NK1 tachykinin agonist, [Pro9]-SP sulphone (1 microM), exerted potent
      bronchodilator actions on carbachol-contracted mouse bronchial preparations. In
      contrast, neither [beta Ala8]-NKA (4-10) nor [MePhe7]-NKB (both at a
      concentration of 1 microM), selective synthetic agonists for NK2 and NK3
      receptors, exerted significant relaxant effects. Furthermore, the selective NK1
      tachykinin antagonist, (+/-)-CP 96,345 (1 microM), abolished substance P (1 nM)-
      but not isoprenaline (0.1 microM)-induced relaxations. 4. Application of
      electrical field stimulation (EFS) (20 Hz, supramaximal voltage, 0.5 ms for 10 s)
      to carbachol-contracted preparations evoked a transient contraction followed by a
      relaxation. The tetrodotoxin-sensitive slow component of this relaxation was
      reduced following capsaicin desensitization. 5. In the presence of indomethacin
      (5 microM) the relaxation induced by substance P, capsaicin or EFS was
      suppressed.6. In conclusion, the mouse main bronchus appears to be a
      monoreceptorial tissue containing only NK, receptors which subserve
      bronchodilator functions. Such receptors could be activated by exogenous or
      endogenously (capsaicin or EFS) released tachykinins and the consequent
      relaxation is probably mediated by the generation of prostanoids.

PMID- 1380378
TI  - FR 113680: a novel tripeptide substance P antagonist with NK1 receptor
      selectivity.
AB  - 1. We have discovered a novel tripeptide substance P (SP) antagonist, FR 113680
      [N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N'-formyl-D- tryptophyl]-N-methyl-N
      phenylmethyl-L-phenylalaninamide]. In binding experiments, FR 113680 inhibited
      [3H]-SP binding to guinea-pig lung membranes (NK1) in a competitive manner but
      had not effect on [3H]-SP binding to rat cerebral cortical membranes (NK1), [3H]
      neurokinin A ([3H]-NKA) binding to rat duodenum smooth muscle membranes (NK2) and
      [3H]-eledoisin (Ele) binding to rat cerebral cortical membranes (NK3). 2. In
      bioassay experiments, FR 113680 dose-dependently inhibited SP-induced guinea-pig
      ileum contraction (NK1), but did not inhibit either NKA-induced rat vas deferens
      contraction (NK2) or neurokinin B (NKB)-induced contraction of rat portal vein
      (NK3). According to Schild plot analysis, the inhibitory effect of FR 113680 on
      SP-induced guinea-pig ileum contraction is competitive and the pA2 value is 7.53.
      3. The inactivity of FR 113680 on NK1 receptors in rat compared to guinea-pig may
      represent species-specific forms of the NK1 receptor. 4. These findings suggest
      that FR 113680 interacts selectively with the NK1 neurokinin receptor.

PMID- 1380377
TI  - Chloride channels and anion fluxes in a human colonic epithelium (HCA-7).
AB  - 1. Colonic epithelial cells, derived from a human adenocarcinoma (HCA-7), were
      examined by the patch clamp technique. 2. Outwardly rectifying anion (Cl-)
      channels were identified in the apical membrane. The conductance was g(in)
      approximately 26 pS, g(out) approximately 40 pS. The open state probability of
      the channels increased with depolarization and the selectivity for Cl- over K+
      (PCl/PK) was approximately 7.5. 3. The channels were sensitive to intracellular
      adenosine 3':5'-cyclic monophosphate (cyclic AMP, 0.1 mM), but not to Ca2+ (at
      concentrations up to 1 mM). At depolarized potentials the channels were blocked
      by pirentanide (1-5 microM) applied intracellularly. 4. HCA-7 monolayers loaded
      with 125I- (as a marker for Cl-) were used to measure I- efflux and converted to
      instantaneous rate constants. 5. The rate constant for I- efflux was increased by
      forskolin and lysylbradykinin (LBK). The effects of forskolin were not effected
      by BAPTA (an intracellular calcium chelator). The effects of LBK were inhibited
      by BAPTA and by Ba2+, indicating that LBK raised intracellular Ca2+ (Cai) which
      activates Ca(2+)-sensitive K-channels, the latter being blocked by Ba2+. 6.
      Although it cannot be conclusively proved that the outwardly rectifying chloride
      channels described here are solely or partially responsible for the increased
      anion efflux or transepithelial chloride secretion, the channels are likely to be
      more relevant for cyclic AMP-requiring rather than Ca(2+)-requiring
      secretagogues.

PMID- 1380379
TI  - Endothelium-dependent relaxation to acetylcholine in the rabbit basilar artery:
      importance of membrane hyperpolarization.
AB  - 1. Muscarinic stimulation of isolated, preconstricted segments of the basilar
      artery, with either acetylcholine or carbachol, was followed by endothelium
      dependent smooth muscle relaxation and membrane hyperpolarization. 2. Smooth
      muscle relaxation to acetylcholine was stimulated in the presence of lower
      concentrations than the associated hyperpolarization (EC50 values 3.2 microM and
      31.6 microM, respectively), and was sustained during agonist application, while
      the hyperpolarization was relatively transient. 3. Repeated exposure to
      acetylcholine was associated with loss of membrane hyperpolarization, while
      smooth muscle relaxation was unaltered. Following a second exposure to 100 microM
      acetylcholine, mean hyperpolarization was markedly depressed from 8.5 to 2 mV,
      and subsequent exposures failed to induce any hyperpolarization. Relaxations with
      a similar amplitude and rate of development, were recorded with each subsequent
      addition of acetylcholine. 4. The competitive substrate inhibitors for nitric
      oxide synthase, L-NG-monomethyl arginine (100 microM L-NMMA) or L-NG-nitro
      arginine methyl ester (100 microM L-NAME), modified the form and amplitude of
      both the relaxation and the hyperpolarization to acetylcholine. In the majority
      of experiments, both the hyperpolarization and the relaxation were almost totally
      abolished. 5. Neither nitric oxide, applied directly in physiological salt
      solution, nor sodium nitroprusside, produced smooth muscle hyperpolarization
      except in high concentrations. Reproducible, small amplitude (around 2 mV)
      hyperpolarization followed the application of either NO gas (15 microM) or sodium
      nitroprusside (100 microM), both of which induced almost maximal smooth muscle
      relaxation. 6. These data show that muscarinic stimulation of endothelial cells
      in the rabbit basilar artery is followed by both smooth muscle hyperpolarization
      and relaxation. They indicate that nitric oxide is involved in both of these
      responses, but that the smooth muscle hyperpolarization is not an essential
      component of the relaxation.

PMID- 1380380
TI  - Kinetic modulation of guinea-pig cardiac L-type calcium channels by fendiline and
      reversal of the effects of Bay K 8644.
AB  - 1. The modulation of L-type calcium channel current (ICa) by fendiline, a
      diphenylalkylamine type of calcium channel blocker was investigated on guinea-pig
      ventricular myocytes by use of the whole-cell patch-clamp technique. 2. Fendiline
      induced block of ICa is accompanied by modulation of the channel kinetics in a
      complex manner. The time course of ICa inactivation is significantly faster and
      the channel availability (f infinity) curve is shifted considerably to more
      negative potentials by fendiline. These findings can be interpreted qualitatively
      in terms of a modulated receptor. 3. When the 1,4-dihydropyridine agonist (4R,
      4S)-Bay K 8644 was added in presence of 30 microM fendiline a further reduction
      of ICa instead of the expected stimulatory effect was observed. 4. A similar
      'paradoxical' inhibition of ICa was produced by the pure agonist enantiomer (4S)
      Bay K 8644. Thus this novel effect of Bay K 8644 cannot be attributed to changes
      in affinity of the 1,4-dihydropyridine receptor site for (4R)-Bay K 8644 during
      fendiline action. 5. The IC50 for fendiline was reduced to 3.0 +/- 0.1 microM
      (control value: 17.0 +/- 2.4 microM) and the Hill slope in its presence was
      increased to 1.90 +/- 0.1 (control value: 1.39 +/- 0.23) by 1 microM (4R, 4S)-Bay
      K 8644. 6. (4R,4S)-Bay K 8644 caused the expected stimulation of ICa in the
      presence of verapamil, diltiazem and nifedipine, overcoming the inhibitory effect
      of these calcium channel blockers. 7. The 'paradoxical' inhibitory effect of the
      agonist Bay K 8644 can be explained in terms of an allosteric interaction between
      fendiline and the dihydropyridine agonist.

PMID- 1380381
TI  - The effect of monoclonal antibodies to calcitonin gene-related peptide (CGRP) on
      CGRP-induced vasodilatation in pig coronary artery rings.
AB  - 1. The modification of the vasodilator effect of calcitonin gene-related peptide
      (CGRP) by a panel of monoclonal antibodies (MAbs), which map to discrete epitopes
      on the CGRP molecule, was investigated in pig coronary artery rings (PCA). The
      preparations were pre-constricted with acetylcholine (3 x 10(-7) M) and
      concentration-response curves to CGRP (2 x 10(-10)-2.56 x 10(-8) M) were obtained
      in the presence or absence of each MAb. 2. CGRP caused a concentration-dependent
      relaxation of PCAs which reached a maximum (98.2 +/- 4.8%, n = 25) at 1.28 x 10(
      8) M and gave an EC50 of 3.8 +/- 0.8 x 10(-9) M. 3. Two MAbs which map to the N
      terminal, CN1 and CRA3, did not affect the CGRP response whilst a third, CRA5,
      significantly inhibited its effect. 4. The C-terminal MAb, CRA2, did not modify
      the CGRP response whilst, in contrast, CB3 (C-terminal) potentiated its effect. A
      similar augmentation of the CGRP-induced vasodilatation was seen in the presence
      of the middle-region MAb, CRA8. 5. These results suggest that regional specific
      MAbs can modify the vasodilator effect of CGRP causing either inhibition (CRA5, N
      terminal) or potentiation (CB3, C-terminal; CRA8, middle region).

PMID- 1380382
TI  - Actions of arginine polyamine on voltage and ligand-activated whole cell currents
      recorded from cultured neurones.
AB  - 1. Toxins from invertebrates have proved useful tools for investigation of the
      properties of ion channels. In this study we describe the actions of arginine
      polyamine which is believed to be a close analogue of FTX, a polyamine isolated
      from the American funnel web spider, Agelenopsis aperta. 2. Voltage-activated
      Ca2+ currents and Ca(2+)-dependent Cl- currents recorded from rat cultured dorsal
      root ganglion neurones were reversibly inhibited by arginine polyamine (AP; 0.001
      to 100 microM). Low voltage-activated T-type Ca2+ currents were significantly
      more sensitive to AP than high voltage-activated Ca2+ currents. The IC50 values
      for the actions of AP on low and high voltage-activated Ca2+ currents were 10 nM
      and 3 microM respectively. AP was equally effective in inhibiting high voltage
      activated currents carried by Ba2+, Sr2+ or Ca2+. However, AP-induced inhibition
      of Ca2+ currents was attenuated by increasing the extracellular Ca2+
      concentration from 2 mM to 10 mM. 3. The actions of AP on a Ca(2+)-independent K+
      current were more complex, 1 microM AP enhanced this current but 10 microM AP had
      a dual action, initially enhancing but then inhibiting the K+ current. 4. gamma
      Aminobutyric acid-activated Cl- currents were also reversibly inhibited by 1 to
      10 microM AP. In contrast N-methyl-D-aspartate currents recorded from rat
      cultured cerebellar neurones were greatly enhanced by 10 microM AP. 5. We
      conclude that at a concentration of 10 nM, AP is a selective inhibitor of low
      threshold T-type voltage-activated Ca2+ currents. However, at higher
      concentrations 1-10 microM AP interacts with ion channels or other membrane
      constituents to produce a variety of actions on both voltage and ligand gated ion
      channels.

PMID- 1380383
TI  - Adenosine modulation of calcium currents in postganglionic neurones of avian
      cultured ciliary ganglia.
AB  - 1. Calcium currents in postganglionic neurones of cultured 7- to 10-day embryonic
      avian ciliary ganglia were analyzed under whole-cell voltage-clamp and their
      modulation by 2-chloroadenosine determined. 2. In the presence of tetrodotoxin
      (200 nM) in the medium to block the Na+ current and CsCl (105 mM) in the patch
      clamp electrode to block the K+ current, two different components of the calcium
      currents (transient and sustained) were identified on the basis of their voltage
      dependent kinetics as well as their sensitivity to the dihydropyridine agonist
      Bay K 8644 and antagonist nifedipine. 3. The sustained current inactivated very
      slowly (tau greater than 1000 ms; for test potentials from -20 mV to +40 mV) but
      was reactivated at a holding potential (Vh) of -40 mV. The current was increased
      on average over 50% by 1 microM of Bay K 8644 at a test potential of 0 mV and
      decreased over 35% by 1 microM of nifedipine. 4. The transient current
      inactivated slowly (tau less than 200 ms; for test potentials from -20 mV to +40
      mV), and could be completely reactivated at a Vh of -80 mV. This current was
      unaffected by Bay K 8644 (1 microM) but reduced on average by 8% with nifedipine
      (1 microM). 5. The sustained and transient currents were decreased more than 70%
      by 5 microM of omega-conotoxin and decreased more than 50% by 250 microM
      verapamil. 6. 2-Chloroadenosine (1 microM) decreased the transient current by
      over 50% and the sustained current by less than 10%. In the presence of
      nifedipine (1 microM), 2-chloroadenosine decreased the transient current by over
      30% and the remaining sustained current by 35%.In the presence of 8
      phenyltheophylline (10 microM), 2-chloroadenosine no longer decreased either the
      transient or sustained currents but did have a slight potentiating effect on both
      the transient and sustained currents.7. These observations of the effects of 2
      chloroadenosine on the transient and sustained currents are discussed in relation
      to the different calcium channel types at preganglionic nerve terminals.

PMID- 1380384
TI  - Stimulation of noradrenaline release in human cerebral cortex mediated by N
      methyl-D-aspartate (NMDA) and non-NMDA receptors.
AB  - 1. Human brain cortical slices from patients undergoing neurosurgery for
      treatment of epilepsy resistant to antiepileptic drugs were used to identify and
      characterize N-methyl-D-aspartate (NMDA) and non-NMDA receptors mediating
      stimulation of noradrenaline release. The slices preincubated with [3H]
      noradrenaline were superfused with Krebs-Henseleit solution with or without Mg2+
      (1.2 mmol l-1) and were stimulated by 2-min exposure to NMDA, kainic acid or (RS)
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). 2. In slices
      superfused without Mg2+, NMDA induced a concentration-dependent tritium overflow.
      3. The NMDA-evoked tritium overflow was almost abolished by tetrodotoxin (TTX),
      Mg2+ or by omission of Ca2+ from the superfusion fluid. 2-Amino-5
      phosphonopentanoic acid (AP5; a competitive NMDA receptor antagonist) or
      dizocilpine (formerly MK-801; an antagonist at the phencyclidine receptor within
      the NMDA-gated ion channel) inhibited the NMDA-evoked tritium overflow. The
      stimulatory effect of NMDA was not significantly enhanced by glycine added to the
      superfusion fluid but was reduced by 7-chlorokynurenic acid (an antagonist at the
      glycine site coupled to the NMDA receptor). 4. In slices superfused with solution
      containing Mg2+, kainic acid or AMPA induced a concentration-dependent tritium
      overflow which was susceptible to blockade by TTX. 5. The kainic acid-evoked
      tritium overflow was not affected by DL-(E)-2-amino-4-methyl-5-phosphono-3
      pentanoic acid (CGP37849; a competitive NMDA receptor antagonist), but was
      inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; an antagonist at
      glutamate receptors of the non-NMDA type). 6. The AMPA-evoked tritium overflow
      was also inhibited by CNQX.2n

PMID- 1380385
TI  - Penicillin-induced potentiation of glycine receptor-operated chloride current in
      rat ventro-medial hypothalamic neurones.
AB  - 1. Effects of penicillin G (PCN) on glycine (Gly)-evoked Cl- current (IGly) were
      investigated in acutely dissociated rat ventro-medial hypothalamic (VMH) neurones
      by the whole cell mode of patch clamp technique. 2. When PCN was applied
      simultaneously with Gly, PCN depressed IGly like a Cl- channel blocker. 3. The
      PCN-induced blocking action was clearly observed at a low PCN concentration (30
      u), while the maximal blockade was achieved by 600 u (units per 10 ml) PCN. 4.
      When tested solution containing both PCN and Gly was quickly substituted with one
      containing Gly only, a new rebound-like transient current (I(T)) which also
      passed through Cl- channel, was elicited. 5. The peak amplitude of I(T) induced
      by PCN at concentrations higher than 100 u was greater than that induced by
      glycine alone. We termed this phenomenon PCN-induced potentiation of IGly. In all
      cells tested, PCN potentiated IGly. 6. At a lower PCN concentration below 30 u,
      I(T) generation was not clear in the presence of 10(-5) M gamma-aminobutyric
      acid. With PCN a higher concentration than 300 u, I(T) amplitude was greater than
      that of the original peak IGly. This was observed in 18 neurones out of 21. The
      maximal amplitude of the I(T) was achieved with 600 u PCN.

PMID- 1380386
TI  - Comparison of the contractile effects of endothelin-1 and sarafotoxin S6b in goat
      isolated cerebral arteries.
AB  - 1. The effects of endothelium-derived endothelin-1 and snake venom-derived
      sarafotoxin S6b, peptides with striking structural and functional similarities,
      were examined and compared in isolated middle cerebral arteries of goats. 2.
      Endothelin-1 and sarafotoxin S6b contracted cerebral arteries in a concentration
      dependent manner. The potency of endothelin-1 (EC50 = 4.9 (3.9-6.2) x 10(-10) M)
      was about ten times higher than that of sarafotoxin S6b (EC50 = 5.5 (4.4-6.9) x
      10(-9) M). The tension returned to basal values after repeated washings and
      contraction with endothelin-1 could be reproduced. Endothelin-1 and sarafotoxin
      S6b induced further contraction in arteries precontracted with prostaglandin F2
      alpha (10(-5) M). 3. Mechanical removal of the endothelium or incubation with
      indomethacin (10(-5) M) displaced the concentration-response curves to endothelin
      1 and, more pronouncedly, to sarafotoxin S6b to the left. The maximum response to
      sarafotoxin S6b was also increased by either of these two treatments. 4.
      Incubation in 'nominally' Ca(2+)-free medium attenuated the vasoconstrictor
      response to endothelin-1 but not to sarafotoxin S6b, which was inhibited after
      incubation in Ca(2+)-free medium to which EGTA (10(-4) M) had been added.
      Pretreatment with caffeine (2 x 10(-2) M) in Ca(2+)-free medium abolished
      responses to endothelin-1 and sarafotoxin S6b. 5. Bay K 8644 (10(-10) M, 10(-8)
      M) enhanced and nicardipine (10(-10) M, 10(-8) M) inhibited in a concentration
      dependent manner vasoconstrictor response to endothelin-1. Response to
      sarafotoxin S6b was only affected by 10(-8) M Bay K 8644 or nicardipine.6. It is
      concluded that endothelin-1 and sarafotoxin S6b are potent vasoconstrictors of
      goat cerebral arteries, having direct effects on smooth muscle which are
      counteracted by the endothelium through the release of a vasodilatator substance,
      probably prostacyclin. Both endothelin-l and sarafotoxin S6b depend on
      extracellular Ca2+ and on intracellular, caffeine-sensitive Ca2+ stores to
      develop vasoconstriction.However, endothelin-l depends to a larger extent than
      sarafotoxin S6b on free extracellular Ca2+.

PMID- 1380387
TI  - Kinetics of nicotinic acetylcholine ion channels in the presence of intravenous
      anaesthetics and induction agents.
AB  - 1. Single channel currents activated by 250 nM acetylcholine were recorded from
      cell-attached patches of BC3H1 mouse tumour cells grown in culture. Channels were
      recorded in the absence and presence of alphaxalone, diazepam, etomidate,
      fentanyl, ketamine, meperidine, or propofol. 2. All of the anaesthetics tested
      shortened channel open time but did not alter single channel current amplitude.
      Drug concentrations calculated to reduce the time constant of open-time
      distributions by 50% were 99 microM alphaxalone, 66 microM diazepam, 57 microM
      etomidate, 26 microM fentanyl, 15 microM ketamine, 16 microM meperidine, or 81
      microM propofol. 3. Ketamine, meperidine, and propofol reduced channel open time
      at concentrations comparable to plasma levels attained during therapeutic use of
      these agents, while alphaxalone, diazepam, etomidate, and fentanyl reduced
      channel open time only at levels higher than those encountered clinically. 4. The
      potency of these drugs in decreasing channel open time appears to be directly
      correlated with their octanol/buffer partition coefficients. In contrast to
      expectations, however, agents with higher partition coefficients were less potent
      in altering channel open time. 5. Ketamine and meperidine produced a prominent
      third component in closed-time distributions, which were otherwise well described
      by the sum of two exponential components. Alphaxalone, diazepam, and etomidate
      also produced a small third component, while no additional component was seen
      with propofol or fentanyl. These additional components probably arise from
      creation of an additional closed state of the channel. 6. We conclude that these
      agents are not altering channel properties merely by exerting non-specific
      effects via the lipid bilayer and that they are probably not all acting by
      similar mechanisms.

PMID- 1380388
TI  - Effect of human recombinant interleukin-5 on in vitro responsiveness to PAF of
      lung from actively sensitized guinea-pigs.
AB  - 1. The intra-tracheal (i.t.) administration of human recombinant interleukin-5
      (rhIL-5; 100 or 300 ng) to isolated perfused lungs from guinea-pigs actively
      sensitized to ovalbumin induced an increased bronchoconstriction and release of
      thromboxane A2 (TXA2) and histamine into the lung effluent following the
      subsequent (10 min) intra-arterial injection of platelet-activating factor (PAF).
      Lung responses to 5-hydroxytryptamine were unaffected by rhIL-5. 2.
      Hyperresponsiveness to PAF was observed when the lungs were obtained from guinea
      pigs used 2 or 7 days after a booster injection of the antigen and, to a lower
      extent, when they were from animals sensitized by a single antigen
      administration. By contrast, rhIL-5 did not modify the responses to PAF of lungs
      from passively sensitized or from adjuvant-treated guinea-pigs, suggesting that
      immunological stimulation is required to allow the expression of synergism
      between rhIL-5 and PAF. 3. Guinea-pigs killed 2 and 7 days after the booster
      injection of the antigen exhibited a marked increase in the number of eosinophils
      in the bronchoalveolar lavage fluid (BAL), as compared to non-sensitized animals.
      4. Our results demonstrate that rhIL-5 and PAF act synergistically to induce
      enhanced bronchoconstriction and mediator release exclusively when lungs are
      obtained from guinea-pigs sensitized once to ovalbumin and then boosted. Since
      recruitment of eosinophils into the airways and the development of
      hyperresponsiveness to PAF are concomitant, it is suggested that eosinophils are
      the target cells for interaction between rhIL-5 and PAF.

PMID- 1380389
TI  - Calcitonin gene-related peptide increases blood flow and potentiates plasma
      protein extravasation in the rat knee joint.
AB  - 1. The effects of calcitonin gene-related peptide (CGRP) and other vasoactive
      mediators of inflammation on blood flow in the synovial vessels and plasma
      protein extravasation into the knee (femoro-tibial) joint of the pentobarbitone
      anaesthetized rat were measured. 2. Changes in synovial blood flow were estimated
      by 133xenon clearance from the synovial cavity. CGRP (0.1 pmol and 10 pmol) and
      prostaglandin E1 (PGE1; 3 pmol and 300 pmol) significantly increased clearance
      from the knee joint measured 5 min after intra-articular injection. Substance P
      (10 pmol) had no effect on synovial blood flow. 3. Intra-articular perfusion of
      the rat knee with CGRP at concentrations up to 0.1 mM, or PGE1 at concentrations
      up to 10 microM, did not increase plasma extravasation into the synovial cavity
      measured by accumulation of intravenously injected 125I-albumin in the perfusate.
      4. Plasma extravasation into the knee was significantly increased by infusion of
      bradykinin (0.1 microM), 5-hydroxytryptamine (1 microM) and histamine (0.1 mM),
      compared with the contralateral joints in the same animals which were perfused
      with Tyrode solution. 5. Perfusion of the knee joint with substance P did not
      specifically induce 125I-labelled albumin accumulation in the synovial cavity
      even at doses that had systemic effects as observed by marked plasma
      extravasation into other tissues. 6. The increase in plasma extravasation induced
      by histamine (0.1 mM) was potentiated by co-infusion with CGRP (0.1 microM) and
      PGE1 (3 microM). However the response to a submaximal dose (0.1 microM) of
      bradykinin, which induced similar plasma extravasation to histamine (0.1 mM), was
      not increased by co-infusion with CGRP or PGE1.7. These results show that CGRP is
      a potent vasodilator in the rat knee. CGRP released from sensory nerves may act
      synergistically with mediators of increased vascular permeability to modify the
      inflammatory response in this site.

PMID- 1380390
TI  - Long-term potentiation is associated with increased [3H]AMPA binding in rat
      hippocampus.
AB  - The location and nature of the changes underlying long-term potentiation (LTP)
      remain controversial issues. In this study, we tested the possibility that
      changes in binding properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate (AMPA/quisqualate and N-methyl-D-aspartate (NMDA) subtype of glutamate
      receptors are associated with LTP. LTP was elicited in vivo by stimulation of the
      perforant pathway in anesthetized rats. One hour following stimulation the
      animals were sacrificed. We performed quantitative ligand binding autoradiography
      on frozen brain sections using [3H]AMPA and [3H]N-(1-(2-thienyl)cyclohexyl)-3,4
      piperidine ([3H]TCP) to label the AMPA/quisqualate and the NMDA receptors,
      respectively. No changes in [3H]TCP binding were detected in any of the treatment
      groups. However, increases in [3H]AMPA binding were observed only in animals that
      exhibited LTP. These increases were bilateral and present in several subfields of
      the hippocampus and cortical areas. Administration of the NMDA receptor
      antagonist, ketamine, prior to tetanic stimulation prevented both the increase in
      binding and the induction of LTP. These results suggest that changes in the
      characteristics of AMPA/quisqualate receptors are a biochemical correlate of LTP.

PMID- 1380391
TI  - Age-related differences in proliferative responses of Schwann cells during
      Wallerian degeneration.
AB  - Age-related differences in proliferative responses of Schwann cells during
      Wallerian degeneration were investigated in the mouse sciatic nerves after nerve
      transection at 3, 10 and 60 days of age, corresponding to the periods of early
      myelination, active myelination and post-myelination. As assessed by thymidine
      incorporation for the first 24 h in culture, Schwann cells from adult nerve
      proliferated rapidly within day 1 post-transection and reached a peak at day 3.
      In the nerves from neonatal or suckling mice, however, division rate of Schwann
      cells declined after transection, and was even less in the transected nerves than
      in the contralateral uninjured nerves. The reduction in thymidine uptake by
      Schwann cells was more pronounced in nerves sectioned at postnatal day 3 than
      those sectioned at day 10. By contrast, fibroblasts divided rapidly following
      transection regardless of age. These data suggest that mitogens from myelin
      components are important for proliferation of Schwann cells and that in the
      degenerating nerves of young mice, mitotic capacity of Schwann cells declined due
      to not only a loss of axonal mitogens but also the paucity of mitogens from
      myelin components. Proliferation of fibroblasts is likely to be stimulated by
      more general growth-promoting polypeptides common to any other tissues during
      wound repair.

PMID- 1380392
TI  - Evidence for a substance P containing subpopulation in the primate
      suprachiasmatic nucleus.
AB  - Immunohistochemical detection of substance P (SP) in the suprachiasmatic nucleus
      (SCN) of the Old World monkey, Macaca fascicularis, was performed using two
      different rabbit polyclonal antisera. Immunostaining revealed a large population
      of neurons located in the dorsal subdivision of the nucleus identified by Nissl
      stain. This neuronal group represents the only cluster of SP-like immunoreactive
      (SP-IR) perikarya observed within the hypothalamus. In contrast with our present
      finding in the macaque, earlier studies only reported a few scattered SP-IR
      neurons in the SCN of other mammalian species. In agreement with previous
      descriptions of neuropeptides in the SCN, the topographical distribution of SP-IR
      neurons in the monkey confirms that cellular segregation is a significant feature
      of the mammalian SCN. This particular peptidergic subpopulation may represent a
      characteristic of the monkey circadian pacemaker. Together with other anatomical
      data previously reported in monkey and man, this finding also relates to the
      anatomical evolution of the circadian system from non-primates to humans.
      Although convincing data support the implication of SP in cyclic neuroendocrine
      regulations, the role of this tachykinin in circadian rhythmicity remains to be
      elucidated.

PMID- 1380393
TI  - The segmental distribution of afferent fibers from the vaginal cervix and
      hypogastric nerve in rats.
AB  - Injections of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) into the
      walls of the vagina and cervix (vaginocervical injections) of rats resulted in
      labeling of dorsal root ganglia (DRG) cells located at T11-L4 and L6-S2. In a
      second group of animals, exposure of the hypogastric nerve to HRP-WGA resulted in
      a similar bimodal distribution of labeled cells as compared to vaginocervical
      injections. In a third group, unilateral hypogastric nerve transection prior to
      injection of HRP-WGA into the vaginocervical walls resulted in a significant
      reduction in DRG cells labeled at T13, L1, L2, L6 and S1. Bilateral transection
      of the hypogastric nerves prior to vaginocervical injections eliminated labeled
      DRG cells at thoracolumbar levels but not at L6 and S1. Bilateral pelvic
      neurectomy reduced, but did not eliminate labeled DRG cells at L6 and S1
      following vaginocervical injections. These results indicate that the hypogastric
      nerve constitutes a major sensory pathway from the vaginocervical walls to
      thoracic, lumbar and sacral levels of the spinal cord. The hypogastric nerve may
      subserve the transmission of noxious input from the vaginocervical walls as well
      as the activation of ascending spinal pathways involved in neuroendocrine
      reflexes during parturition.

PMID- 1380394
TI  - N-methyl-D-aspartate (NMDA) and opioid receptors mediate dynorphin-induced spinal
      cord injury: behavioral and histological studies.
AB  - Both N-methyl-D-aspartate (NMDA) and opioid receptors have been implicated in the
      pathophysiology of traumatic spinal cord injury and dynorphin-induced paralysis.
      The present studies compared the effects of the non-competitive NMDA antagonist
      dextrorphan (Dex) and the kappa-selective opioid antagonist nor-binaltorphimine
      (nor-BNI) on the acute motor deficits and chronic neuropathological alterations
      caused by intrathecally administered dynorphin A-(1-17) (Dyn A). Infusion of Dyn
      A into the rat lower thoracic spinal subarachnoid space produced acute,
      reversible hindlimb paresis. Histological evaluations of spinal cord sections
      from these animals at 2 weeks post-infusion revealed ventral grey matter
      necrosis, neuronal loss and gliosis as well as axonal loss in adjacent white
      matter; however, there was minimal alteration in serotonin immunocytochemistry
      caudal to the injury zone. Dex or non-BNI pretreatment each significantly (P less
      than 0.05) reduced, and to a similar degree, the acute motor deficits and certain
      histological changes associated with Dyn A administration. These findings further
      support the hypothesis that dynorphin-induced spinal cord injury involves both
      NMDA receptors and opioid receptors.

PMID- 1380395
TI  - Intraseptal connections redefined: lack of a lateral septum to medial septum
      path.
AB  - The integrity of the septohippocampal system is essential for memory formation
      and spatial behavior as well as for the electrical stability of the hippocampus.
      For many years it has been tacitly assumed or explicitly stated that the
      reciprocal septohippocampal loop is closed by a massive lateral septum-medial
      septum path. In the present study we reexamined the intraseptal connectivity with
      Phaseolus vulgaris leucoagglutinin tracing combined with choline
      acetyltransferase and parvalbumin immunohistochemistry at both the light and
      electron microscopic levels. We found that the previously hypothesized lateral
      septum to medial septum projection is extremely sparse and that the major medial
      septum to lateral septum path is parvalbumin-immunoreactive (likely GABAergic).
      The redefined circuitry has important implications for the understanding of the
      septal regulation of hippocampal electrical activity and the operations of the
      septo-hippocampal system.

PMID- 1380396
TI  - Presence of GABA-immunoreactive neurons within intracortical patches in area 18
      of the cat.
AB  - In cat visual cortex, horizontal, intracortical connections spread laterally to
      link together specific columnar sites. When visualized by retrograde tracers,
      these intracortical connections appear as periodic, columnar patches of dense
      cellular labeling interspersed with areas of much less dense labeling. We looked
      for anatomical evidence for direct inhibition among the patchy, horizontal
      connections in area 18, by combining retrograde labeling using wheat germ
      agglutinin (WGA) conjugated to horseradish peroxidase (HRP) with
      immunohistochemistry using an antiserum against the inhibitory neurotransmitter
      gamma-amino butyric acid (GABA). We found numerous double-labeled cells
      associated with some, but not all, of the local patches nearest to the injection
      site. In the superficial layers, the GABA-immunoreactive cells also labeled with
      WGA-HRP were confined to a zone approximately 1.0 mm from the center of the
      injection, while the double-labeled cells in the deeper layers spanned greater
      distances, up to 3.0 mm from the injection center. These more distant, double
      labeled cells in the deeper layers were located on the edges or outside of the
      patches of dense labeling. Thus, all of the more distant intracortical patches,
      as well as some of the more proximal patches were devoid of double-labeled cells-
      a finding which suggests that direct inhibition may occur among only a selected
      group of the 'short range' intracortical patches and among none of the long-range
      patches.

PMID- 1380397
TI  - Stimulation of inositol phosphate formation in cultured human retinal pigment
      epithelium.
AB  - Several hormones, neurotransmitters, and neuropeptides were screened for the
      ability to stimulate inositol phosphate formation in cultured human retinal
      epithelial (RPE) cells. Carbachol, vasopressin and thrombin were found to be
      effective. Treatment of RPE cells with all three agents produced increases in
      inositol monophosphate, inositol bisphosphate and inositol trisphosphate in the
      presence of 10 mM LiCl. Carbachol stimulated a 4-fold increase in the total of
      inositol phosphates at 1 mM. Studies with cholinergic antagonists showed a rank
      order of 4 DAMP greater than QNX greater than pirenzepine greater than
      methoctramine, suggesting the presence of M3 muscarinic receptors. Vasopressin
      gave a 2.5-fold stimulation at 10 microM. Agonists of vasopressin were also
      tested and gave differential responses. Studies using a V1 agonist (PIOVP) and a
      V2 agonist (DAVP) showed DAVP matching the level of stimulation elicited by
      vasopressin whereas treatment with PIOVP only reached 50% of the vasopressin
      response. These data suggested the presence of V2 receptors in the RPE cells.
      Several proteases were tested for their ability to stimulate RPE inositol
      phosphates. Thrombin caused a 7-fold increase in inositol phosphate formation at
      1 U/ml, whereas trypsin and plasmin elicited smaller responses (approximately 2
      fold). The thrombin effect was blocked by the thrombin-specific inhibitor,
      hirudin, but not by other protease inhibitors. Several mediators of inflammation
      such as bradykinin, histamine and serotonin were also tested, and they were
      ineffective in stimulating inositol phosphate turnover in the RPE cells.

PMID- 1380398
TI  - Agents that affect calcium influx can change cyclic nucleotide levels in cultured
      chick pineal cells.
AB  - Previous experiments examined interactions among the effects of cyclic AMP and
      calcium-related agents on melatonin output by cultured chick pineal cells, and
      suggested that changes in calcium influx might act through cyclic AMP. Here,
      effects of calcium-related agents and manipulations on cyclic AMP (and cyclic
      GMP) levels are demonstrated directly. These effects support a role for cyclic
      AMP (but not cyclic GMP) in the effects of changes in calcium influx on melatonin
      production by these cells.

PMID- 1380399
TI  - Immunohistochemical characterization of NPY and substance P containing nerve
      terminals in aged and diabetic human sympathetic ganglia.
AB  - To compare the neuropeptide specificity of dystrophic axon formation in aging
      versus diabetic human sympathetic ganglia we have immunohistochemically
      characterized neuropeptide Y (NPY) and substance P containing intraganglionic
      nerve terminals. Prevertebral superior mesenteric but not paravertebral superior
      cervical ganglia developed markedly swollen NPY containing axonal termini with
      both aging and diabetes. Substance P containing nerve terminals failed to develop
      dystrophic changes. Selective loss of classes of nerve terminals may result in
      discrete functional sequellae.

PMID- 1380400
TI  - gamma-Aminobutyric acid, through GABAA receptors, inhibits the potassium
      stimulated release of calcitonin gene-related peptide- but not that of substance
      P-like material from rat spinal cord slices.
AB  - Superfusion of slices of the dorsal zone of the lumbar enlargement with an
      artificial cerebrospinal fluid was used to investigate the possible modulation by
      GABA receptor ligands of the in vitro release of calcitonin gene-related peptide-
      and substance P-like materials (CGRPLM and SPLM) from the rat spinal cord.
      Whereas the spontaneous outflow of both peptides remained unaffected, the K+ (30
      mM)-evoked overflow of CGRPLM could be partially inhibited (approx. -30%) by GABA
      (1 microM-0.1 mM) and muscimol (10 microM-0.1 mM) but not by baclofen (1-10
      microM). Bicuculline methiodide (1 microM) completely prevented the inhibition by
      GABA (1 microM) and muscimol (10 microM) as expected from an action through GABAA
      receptors. By contrast, the K(+)-evoked SPLM overflow was altered neither by GABA
      nor muscimol and baclofen. These data further support that GABA exerts a
      presynaptic inhibitory control of (CGRP-containing) primary afferent fibres
      within the rat dorsal horn.

PMID- 1380401
TI  - Distribution of bulbospinal neurons supplying bilateral innervation to the
      phrenic nucleus in the rat.
AB  - The location of bulbospinal neurons with axon collaterals in both phrenic nuclei
      were determined by injecting two different fluorescent tracers into the right and
      left C4 cervical spinal cord. In contrast to single-labeled neurons that were
      found throughout the rostrocaudal extent of the medulla, the majority of double
      labeled neurons were located in the rostral ventral respiratory group. Only a few
      double-labeled neurons were found in the ventrolateral nucleus of the solitary
      tract. The role of this bilateral pathway in synchronizing the activity of the
      phrenic nucleus is discussed.

PMID- 1380402
TI  - Susceptibility of brain to AMPA induced excitotoxicity transiently peaks during
      early postnatal development.
AB  - The excitatory and excitotoxic actions of the endogenous excitatory amino acid
      (EAA) neurotransmitter, glutamate, are mediated by activation of three common
      subtypes of EAA receptors: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionic acid (AMPA)/quisqualate and kainate receptors. EAA
      neurotransmitter systems play a number of physiological roles in the regulation
      and organization of neural systems during development. However, excessive
      activation of this neurotransmitter system is also implicated in the
      pathophysiology of several forms of acute and chronic brain injury. In this
      study, the susceptibility of the developing rat brain to AMPA/quisqualate
      receptor mediated injury was examined at eight postnatal ages (1-90 days). The
      receptor agonists, AMPA (25 nmol) or quisqualate (100 nmol), were stereotaxically
      microinjected unilaterally into the anterior striatum. The severity of resulting
      brain injury was assessed 5 days later by comparison of reductions in regional
      cortical and striatal cross-sectional areas. Microinjection of AMPA (25 nmol)
      produced widespread unilateral forebrain injury in the intermediate postnatal
      period (days 5-28). The severity of injury resulting from microinjection of a
      fixed dose of AMPA (25 nmol) transiently exceeded the severity of injury in
      adults between PND 5-28 with peak sensitivity occurring near PND 10. At PND 1,
      microinjection of AMPA produced a 24.5 +/- 1.7% reduction in striatal cross
      sectional area, which is similar to the response observed in adult animals, and
      the lesion was confined to the injection site. Susceptibility to AMPA toxicity
      increased 2-fold from PND 1 to PND 5. At PND 10, the age of maximal sensitivity,
      the excitotoxic reaction to AMPA extended throughout the entire cerebral
      hemisphere and the mean striatal cross-sectional area was reduced by 81.7 +/-
      3.9%. With advancing postnatal age, the severity of injury progressively
      diminished and the lesion became confined to the injection site. The
      developmental pattern of sensitivity to AMPA toxicity in other brain regions
      differed although peak sensitivity consistently occurred near PND 10.
      Microinjection of quisqualate produced a developmental pattern of striatal
      susceptibility similar to AMPA although quisqualate was a considerable less
      potent neurotoxin. In additional experiments, the in vivo pharmacology of AMPA
      and quisqualate mediated brain injury was evaluated in a PND 7 rat model in order
      to determine the neurotoxic characteristics and specificity of these agonists in
      vivo. The severity of brain injury was assessed 5 days after intrastriatal
      excitotoxin injection by comparison of cerebral hemisphere weights.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1380403
TI  - Dopaminergic neuron development in rats: biochemical study from prenatal life to
      adulthood.
AB  - Dopaminergic cell development has been studied mainly using morphological
      techniques and especially histofluorescence. However, the biochemical
      characteristics of dopamine (DA) neuron development and its physiological role
      during ontogeny are much less known. In the present article, the biochemical
      development of DA neurons, from day 13 of prenatal life to adulthood, is
      evaluated in Sprague-Dawley rats. DA was first detected on day 14 of gestation.
      The brain increase in this neurotransmitter begins on day 17 in the proencephalon
      and on day 18 in the mesencephalon, reaching on day 20 a level similar to that
      found during adulthood in the latter but not in the former. DA levels in the
      proencephalon rise slowly to adulthood level when compared to DA in the
      mesencephalon. The modifications observed in tyrosine levels are also largely
      similar to those reported for DA. Finally, the study of the first 48 h of life
      shows an increase in tyrosine levels and a decrease in dihydroxyphenylacetic acid
      levels (with a reduction of DA turnover) during the first 4-5 h of postnatal
      life. Since the serotonergic modification was completely different from DA
      modification, we conclude that the biochemical alteration of DA neurons during
      early postnatal development is specific. The present data suggest that DA neurons
      play different roles before and after reaching adult development.

PMID- 1380404
TI  - In vivo Paramecium mutants show that calmodulin orchestrates membrane responses
      to stimuli.
AB  - Paramecium generates a Ca2+ action potential and can be considered a one-cell
      animal. Rises in internal [Ca2+] open membrane channels that specifically pass
      K+, or Na+. Mutational and patch-clamp studies showed that these channels, like
      enzymes, are activated by Ca(2+)-calmodulin. Viable CaM mutants of Paramecium
      have altered transmembrane currents and easily recognizable eccentricities in
      their swimming behavior, i.e. in their responses to ionic, chemical, heat, or
      touch stimuli. Their CaMs have amino-acid substitutions in either C- or N
      terminal lobes but not the central helix. Surprisingly, these mutations naturally
      fall into two classes: C-lobe mutants (S101F, I136T, M145V) have little or no
      Ca(2+)-dependent K+ currents and thus over-react to stimuli. N-lobe mutants
      (E54K, G40E+D50N, V35I+D50N) have little or no Ca(2+)-dependent Na+ current and
      thus under-react to certain stimuli. Each mutation also has pleiotropic effects
      on other ion currents. These results suggest a bipartite separation of CaM
      functions, a separation consistent with the recent studies of Ca(2+)-ATPase by
      Kosk-Kosicka et al. [41, 55]. It appears that a major function of Ca(2+)
      calmodulin in vivo is to orchestrate enzymes and channels, at or near the plasma
      membrane. The orchestrated actions of these effectors are not for vegetative
      growth at steady state but for transient responses to stimuli epitomized by those
      of electrically excitable cells.

PMID- 1380405
TI  - Ca2+/calmodulin-regulated nitric oxide synthases.
AB  - NO synthase (NOS) catalyzes the oxidation of L-arginine to L-citrulline and
      nitric oxide (NO) or a NO-releasing compound. At least three isoforms of NOS
      exist (types I-III). The activities of the type I isoform purified from brain and
      the type III isoform purified from endothelial cells are regulated by the
      intracellular free calcium concentration ([Ca2+]i) and the Ca(2+)-binding protein
      calmodulin. At resting [Ca2+]i, both isozymes are inactive; they become fully
      active at [Ca2+]i greater than or equal to 500 nM Ca2+. Longer lasting increases
      in [Ca2+]i may downregulate NO formation, for in vitro phosphorylation by
      Ca2+/calmodulin protein kinase II decreases the Vmax of NOS. Besides the
      conversion of L-arginine, type I NOS, Ca2+/calmodulin dependently, generates H2O2
      and reduces cytochrome c/P450. Other redox activities, i.e. the reduction of
      nitroblue tetrazolium to diformazan (NADPH-diaphorase) or of quinoid
      dihydrobiopterin to tetrahydrobiopterin, by NOS appear to be Ca2+/calmodulin
      independent.

PMID- 1380406
TI  - The germ cell-less gene product: a posteriorly localized component necessary for
      germ cell development in Drosophila.
AB  - The first cell fate specification process in the Drosophila embryo, formation of
      the germline precursors, requires posteriorly localized germ plasm. We have
      cloned a gene, germ cell-less (gcl), required for germline formation. Posterior
      localization of the gcl messenger RNA (mRNA) requires the function of those genes
      essential for the localization of both nanos RNA, which specifies the abdomen,
      and the germ cell determinants. Mothers with reduced gcl function give rise to
      sterile adult progeny that lack germ cells. In embryos with reduced maternal gcl
      product, the germ cell precursors fail to form properly. Consistent with this
      phenotype, gcl protein specifically associates with those nuclei that later
      become the nuclei of the germ cell precursors. These observations suggest that
      gcl functions in the germ cell specification pathway.

PMID- 1380407
TI  - Biochemical modulation of 5-fluorouracil with or without leucovorin by a low dose
      of brequinar in MGH-U1 cells.
AB  - Combination of low doses of de novo pyrimidine biosynthesis inhibitors with 5
      fluorouracil (FU) has been proposed to increase the antitumor activity of FU.
      Brequinar is such an inhibitor that has little clinical anti-tumor effect when
      used alone. We determined the clonogenic survival of MGH-U1 cells treated with FU
      +/- leucovorin (LV) +/- brequinar and examined the effects of these treatments on
      thymidylate synthase (TS). After 24 h exposure, the concentrations resulting in
      50% inhibition of cell growth (IC50) for brequinar, FU, and FU+LV (100 microM)
      were 0.4, 20, and 10 microM, respectively. Both 24 h pretreatment and 48 h
      continuous treatment with the IC10 (0.1 microM) of brequinar increased the
      cytotoxicity of FU but did not enhance that of FU+LV. Simultaneous 24 h exposure
      to 0.1 microM brequinar and FU +/- LV did not increase the cytotoxicity of FU +/-
      LV. Intracellular cytidine triphosphate (CTP) and uridine triphosphate (UTP)
      pools, free TS binding sites, and levels of free fluorodeoxyuridine monophosphate
      (FdUMP) and deoxyuridine monophosphate (dUMP) were measured in cells pretreated
      with 0.1 microM brequinar for 24 h alone or followed by a 2-h exposure to FU (25
      microM) +/- LV (100 microM). In brequinar-treated cells, CTP and UTP pools
      amounted to 68% and 46% of control values, respectively. The free TS binding
      sites remaining amounted to 70% of control values in cells treated with FU and 9%
      of control levels in those treated with FU+brequinar. Free FdUMP levels increased
      5-fold in cells pretreated with brequinar as compared with those treated with FU
      alone. The increased formation of FdUMP was inhibited by simultaneous exposure to
      100 microM hypoxanthine and 25 microM FU. Intracellular dUMP levels were not
      affected by brequinar. We conclude that a low dose of brequinar increases the
      cytotoxicity of FU but does not enhance that of FU+LV when exposure to brequinar
      precedes FU treatment. This potentiation appears to be mediated by the increased
      formation of FdUMP as a consequence of an increase in the cosubstrate
      phosphoribosyl pyrophosphate (PRPP).

PMID- 1380408
TI  - In vivo effects of doxorubicin on kinase C in cultured cells.
AB  - The ability of doxorubicin to inhibit kinase C in vivo in cultured BALB/c 3T3
      mouse fibroblasts was determined by the phosphorylation of the myristoylated
      alanine-rich C kinase substrate (MARCKS) and the induction of c-fos transcription
      following treatment with 200 nM phorbol 12-myristate 13-acetate. A concentration
      of 60 microM doxorubicin did not inhibit MARCKS phosphorylation but completely
      inhibited c-fos expression. The inhibition of c-fos expression was not
      specifically mediated via kinase C, since both the total RNA synthesis as
      measured by [3H]-uridine uptake and the fraction of serum-induced c-fos
      expression that was not attributable to kinase C were inhibited by doxorubicin.
      The present data do not support the hypothesis that the cytotoxic effect of
      doxorubicin is attributable to the inhibition of kinase C in vivo.

PMID- 1380409
TI  - Tc-99m HMPAO WBC imaging to detect carditis and to evaluate the results of high
      dose gamma globulin treatment in Kawasaki disease.
AB  - Eighteen patients with Kawasaki disease and suspected carditis (11 boys, 7 girls,
      mean age 18 months) in acute stages underwent Tc-99m HMPAO WBC imaging of the
      heart. Signs and symptoms subsided after conventional aspirin therapy and the
      intravenous injection of high-dose (400 mg/kg per day for 5 days) gamma-globulin
      treatments. Tc-99m HMPAO WBC imaging of the heart was arranged a second time to
      evaluate the effects of the treatments for carditis. The results showed that a
      significant difference existed in the severity of carditis before and after the
      treatments (P less than 0.001, by signed rank test), 39% (7/18) with significant
      improvement in severity of carditis, 50% (9/18) without definite change. However,
      11% (2/18) became more severely ill after the treatments. Tc-99m HMPAO WBC
      imaging may be useful in detecting carditis in Kawasaki disease and in evaluating
      the effects of aspirin plus the newly recommended gamma-globulin for the
      treatment of carditis in Kawasaki disease.

PMID- 1380411
TI  - Epoetin enhances erythropoiesis in normal men undergoing repeated phlebotomies.
AB  - Epoetin may enhance autologous blood donation, but efficacy and dose response
      have not been established. This multicenter, double-blind trial compared
      intravenous placebo (n = 23) with epoetin beta, 250 U/kg (n = 23), 500 U/kg (n =
      19), and 1000 U/kg (n = 22), administered three times weekly for 26 days. Normal
      men (age, 28 +/- 7 years; mean +/- SD) received phlebotomies up to three times
      weekly as long as the hemoglobin remained greater than or equal to 12 gm/dl.
      Subjects treated with epoetin donated 32% more units of blood (p less than 0.05)
      compared with placebo. A dose response was not observed. Platelet counts
      increased with epoetin compared with placebo, but platelet function and bleeding
      time did not change. Prothrombin times increased and partial thromboplastin times
      decreased with both epoetin and placebo. The supernatant of packed red blood
      cells collected after multiple phlebotomies and stored 42 days had slightly lower
      glucose concentrations and pH after therapy with epoetin. Blood pressure did not
      change with epoetin or placebo. These findings support the efficacy and safety of
      epoetin for enhancing the erythropoietic response of normal subjects during
      intensive phlebotomy.

PMID- 1380410
TI  - Intrathecal drug administration. Present use and future trends.

PMID- 1380412
TI  - A member of the selectin family (GMP-140/PADGEM) is expressed on thrombin
      stimulated rat platelets in vitro.
AB  - 1. Granule membrane protein (GMP-140) is an integral alpha-granule membrane
      glycoprotein, expressed on the surface of human platelets following
      degranulation, and is part of a new family of adhesion molecules (selectins)
      related to the endothelial leukocyte adhesion molecule (ELAM-1) and to the
      lymphocyte homing receptors in man (Leu-8/TQ1) and in mouse (gp90MEL-14). 2. The
      cross-reactivity with rat platelets of the monoclonal antibodies (MAb), LYP20 and
      S12, directed against human GMP-140 was examined, with the purpose of assessing
      the homology of GMP-140 between human and rat platelets and of using positive
      MAbs to detect platelet activation in vivo in response to vascular disease in
      rats. 3. By ELISA technique, LYP20 gave a greater OD reading with thrombin
      stimulated rat platelets than with resting platelets. 4. 125I-LYP20 bound
      significantly more to thrombin-stimulated rat platelets (3875 +/- 750
      molecules/platelet) than to resting platelets (645 +/- 240 molecules/platelet, P
      less than 0.01) with 50% maximum binding at 0.13 +/- 0.02 microgram/ml; 125I-S12
      did not bind to rat platelets. 5. By fluorescence-activated flow cytometry there
      were significantly more fluorescent thrombin-stimulated platelets (56 +/- 7% of
      total), compared with resting platelets (8 +/- 1% of total, P less than 0.001).
      6. Western blots of rat platelet lysates showed that LYP20 bound to a single band
      identified, under non-reducing conditions, as having the same apparent M(r) as
      GMP-140. 7. LYP20 immunoprecipitated a protein which became radiolabelled on the
      surface of thrombin-activated rat platelets; S12 did not recognize any
      protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380413
TI  - Vasoactive intestinal polypeptide-containing nerve fibers are increased in
      abundance in the choroid of dystrophic RCS rats.
AB  - As photoreceptor degeneration progresses in Royal College of Surgeons (RCS) rats,
      a variety of morphological and physiological alterations occur in the outer
      retina. Since the choriocapillaris responds to changes in the outer retina in
      other retinopathies, we examined the possibility that changes in the choroidal
      vasculature also occur in RCS rats. The choroidal and choriocapillary vessels in
      RCS and control (RCS-rdy+) rats were examined during the period after which
      photoreceptor loss and retinal vascular changes had occurred (7-mos to 28-mos).
      Light microscopic (LM) morphometry and electron microscopic (EM) examination
      showed no significant differences between these groups in the number, size or
      morphology of these vessels. However, EM image analysis revealed that nerve
      fibers and bundles were twice as abundant in the RCS choroid than in the control.
      Using immunohistochemical techniques at the LM level combined with image analysis
      we found that vasoactive intestinal polypeptide positive (VIP+) fibers were
      significantly increased in the RCS choroid compared with control choroid. In
      contrast, the abundance of immunoreactive fibers labelled for substance P and
      dopamine beta hydroxylase appeared similar in both the control and RCS choroid.
      Since VIP is a potent vasodilator, the increased abundance of nerve fibers in the
      RCS choroid in conjunction with the unaltered number and size of these vessels
      suggests that choroidal blood flow may be increased. It is uncertain whether this
      increase is a response to the outer retinal pathology or contributes to it.

PMID- 1380414
TI  - Localization of the lysosomal protease dipeptidyl peptidase II in the young
      normal rat lens: a correlative light and electron microscopic analysis.
AB  - This investigation was follow-up to an earlier biochemical and light microscopic
      histochemical study, in which the lysosomal protease dipeptidyl peptidase II (DPP
      II) was demonstrated in rodent lenses. In the present study, a method was
      employed that allowed a more precise histochemical localization of the enzyme,
      one that was suitable for ultrastructural as well as light microscopic analysis.
      Successful demonstration of the enzyme using either of two synthetic substrates,
      and the significant reduction of the enzyme reaction by phenylmethylsulphonyl
      fluoride (PMSF), a serine protease inhibitor, pointed to the sensitivity of the
      method. A flat-embedding technique allowed the correlative light and electron
      microscopic analysis of specific areas of the specimen. Examination of the
      epithelium and outer cortical regions of the lens revealed the
      compartmentalization of DPP II activity within lysosomal dense bodies that were
      concentrated primarily in the equatorial and sutural regions, and also an
      association of the reaction product with larger bodies that were confined to the
      sutural regions. The latter structures appeared to represent fiber cell fragments
      that were enwrapped with narrow extensions of the surrounding fiber cells. The
      location of enzyme activity within the sutural bodies and also within the
      intercellular spaces of the modified fiber cell extensions surrounding these
      bodies suggested that lysosomal proteases may play a role in the segregation and
      degradation of specific regions of normal lens fiber cells.

PMID- 1380415
TI  - Pathogenesis and immunology in shigellosis: applications for vaccine development.

PMID- 1380416
TI  - Shigella lipopolysaccharide: structure, genetics, and vaccine development.

PMID- 1380417
TI  - Cytogenetics of bisexual/unisexual species of Poecilia. II. Analysis of
      heterochromatin and nucleolar organizer regions in Poecilia mexicana mexicana by
      C-banding and DAPI, quinacrine, chromomycin A3, and silver staining.
AB  - Chromosomes of Poecilia mexicana mexicana, one of the bisexual species involved
      in the hybrid origin of the unisexual teleost fish species P. formosa, were
      analyzed by several staining techniques. Sex-specific, differential
      heterochromatin, found in other congeneric species, was not observed in P. m.
      mexicana. Nucleolar organizer regions were polymorphic among individual specimens
      within a given population sample. A single specimen exhibiting intraindividual
      variability of chromosome pair 1 and a specimen with a triploid karyotype are
      also described.

PMID- 1380418
TI  - Localization by in situ hybridization of a type I keratin intermediate filament
      gene (Krt-1.14) to band D of mouse chromosome 11.
AB  - A probe from the 3' noncoding region of a murine type I keratin intermediate
      filament (IF) gene (Krt-1.14) localizes to band D of murine Chromosome 11 using
      in situ hybridization. This localization provides a physical confirmation of the
      assignment of the type I keratin genes by linkage analysis in the mouse. It also
      demonstrates that the Krt-1.14 genes are at a single locality in the mouse in
      contrast to the two locations on the short and long arms of chromosome 17 in
      humans.

PMID- 1380420
TI  - [Surgical interventions of proximal bile duct tumors. Resectability, forms of
      resection and surgical palliative measures, liver transplantation--a critical
      evaluation of current status].

PMID- 1380419
TI  - Localization of four human chromosome 21 genes--SOD1, ETS2, IFNAR, and CBR--to
      two different chromosomes in the marsupial species Macropus eugenii.
AB  - We have mapped the chromosomal location of four genes previously assigned to
      human chromosome 21--Cu/Zn superoxide dismutase (SOD1), the protooncogene ETS2,
      the interferon alpha/beta receptor gene (IFNAR), and the carbonyl reductase gene
      (CBR)--in the tammar, Macropus eugenii. The genes are localized on two separate
      autosomes: SOD1 and CBR map to chromosome 7 and ETS2 and IFNAR map to chromosome
      3 or 4. These results provide the first example of asynteny between SOD1/CBR and
      ETS2/IFNAR in a mammalian species. The results suggest that either this synteny
      group has been disrupted in the marsupial lineage, or, alternatively, the genes
      located on human chromosome 21 may have been joined after the marsupials diverged
      from the eutherian mammals some 130-150 million years ago.

PMID- 1380421
TI  - [Free intraperitoneal tumors cells in pancreatic cancer--significance for
      clinical course and therapy].
AB  - Intraoperative peritoneal cytology was performed in 36 patients with pancreatic
      ductal adenocarcinoma. 12 patients (33%) showed malignant cells in the peritoneal
      cavity. In the further course these patients developed more non-local metastases
      and had a significantly shorter survival rate. Peritoneal carcinomatosis became
      evident in 75% of the patients with free cancer cells in contrast to only 14% of
      the patients without. Detection of free cancer cells was directly related to the
      histological tumor stage (TNM-system). Iatrogenic shedding of malignant cells by
      surgical tumor manipulation or needle biopsy was not observed. The technique of
      intraoperative peritoneal lavage with consecutive cytology and its possible
      effects on further treatment is discussed.

PMID- 1380422
TI  - [Hemodynamic surveillance in pregnancy induced hypertension during volume
      expansion therapy].
AB  - Hemodynamic parameters were studied in 80 cases of pregnancy induced hypertension
      (PIH) using noninvasive cardiovascular detector (TP-CBS). Women were categorized
      into 3 kinds of hemodynamic patterns: (1) normal cardiac output, 45 cases,
      cardiac index (CI) = 2.5-4 L.min-1/m2; (2) high cardiac output, 10 cases, CI
      greater than 4 L.min-1/m2; (3) low cardiac output, CI less than 4 L.min-1/m2, 25
      cases (31.5%). Ten cases in each category were selected for test after volume
      expansion therapy. MAP decreased in varying degrees. CI showed marked increase in
      the low cardiac output group, but decreased to normal in the high output group.
      The monitoring criteria for protecting against pulmonary edema during volume
      expansion therapy were discussed.

PMID- 1380423
TI  - CD5+ B cells are decreased in peripheral blood of patients with Crohn's disease.
AB  - B cells bearing the CD5 surface marker comprise a substantial minority of the
      circulating lymphocyte population in healthy individuals. These recently
      described cells have been implicated in T-independent humoral responses,
      immunoregulation, and autoimmunity. We undertook to enumerate circulating CD5+ B
      cells by three-color fluorescence activated flow cytometry in 28 patients with
      Crohn's disease (CD). None of the CD patients were using immunosuppressive
      medication. The CD patients were subdivided into "inactive" and "active" groups
      based upon their Crohn's disease activity index (CDAI). Thirty-two normal
      subjects served as a control population. The percentage of CD19+ B cells was
      significantly reduced in both active and inactive CD patients as compared with
      normal controls (P less than or equal to 0.01). CD5+ B cells were likewise found
      to be significantly decreased in both inactive and active CD patients (P less
      than or equal to 0.01) as compared with normal controls. The proportion of CD5+ B
      cells was significantly lower in the peripheral blood of active as compared with
      inactive CD patients (P less than or equal to 0.05). The finding that CD5+ B
      cells are reduced in CD may provide an important clue to immunological
      dysfunction in inflammatory bowel disease and merits further study.

PMID- 1380424
TI  - Role of ischemia in acute pancreatitis. Hemorrhagic shock converts edematous
      pancreatitis to hemorrhagic pancreatitis in rats.
AB  - Ischemia has been considered to play a role in the development of acute
      pancreatitis. The aim of this study was to investigate the effect of ischemia,
      caused by hemorrhagic shock, on cerulein-induced acute pancreatitis in rats.
      Acute pancreatitis was induced by the intravenous infusion of a supramaximally
      stimulating dose of cerulein (10 micrograms/kg/hr) for 6 hr. Hemorrhagic shock
      was induced by the removal of blood until the mean arterial blood pressure
      reached 35 mm Hg. This level was maintained for 30 min, after which time all the
      blood was reinfused. Hemorrhagic shock alone induced no morphological change in
      the pancreas. However, after the induction of hemorrhagic shock in animals
      treated with cerulein, hemorrhage and parenchymal necrosis were frequently
      observed in the pancreas. Seven of 20 rats (35%) receiving cerulein plus
      hemorrhagic shock had died by 48 hr after the start of cerulein infusion, whereas
      none of the rats in the cerulein or shock group died during this experiment.
      Cathepsin B activity in the pancreas of the cerulein plus shock group was
      significantly higher than in the other groups at 48 hr. These results suggest
      that ischemia may be a contributing factor in the pathogenesis of acute
      pancreatitis.

PMID- 1380425
TI  - Histopathologic correlates of serum amylase activity in acute experimental
      pancreatitis.
AB  - The association of serum amylase activity with the extent of pancreatic injury in
      acute pancreatitis is unclear. To clarify this relationship, we induced acute
      pancreatitis ranging from mild to lethal in 118 Sprague-Dawley rats (350-450 g).
      This was achieved by controlled intraductal infusion of low- or high-dose bile
      salt, with or without enterokinase, followed by intravenous cerulein or saline
      for 6 hr. Serum amylase was measured at baseline and 6 hr. Pancreatic
      histopathology was evaluated by two blinded pathologists employing total surface
      scoring (N = 118) and morphometric 20-field documentation (N = 22). Serum amylase
      correlated best with edema (r = 0.61) and fat necrosis (r = 0.58), less well with
      acinar necrosis (r = 0.53) and inflammation (r = 0.50), and poorly with
      hemorrhage (r = 0.33) and perivascular infiltrate (r = 0.31). Inasmuch as edema
      and fat necrosis are not important determinants of severity, these observations
      could explain the poor prognostic value of serum amylase activity in patients
      with acute pancreatitis.

PMID- 1380426
TI  - Effects of long-acting somatostatin analog (SMS 201-995) on eicosanoid synthesis
      and survival in rats with acute necrotizing pancreatitis.
AB  - The effects of a long-acting somatostatin analog (SMS 201-995) were studied in an
      established model of acute necrotizing pancreatitis in rats. SMS 201-995, when
      given prior to induction of pancreatitis, decreased the mortality rate from 100%
      to 40% (P = 0.0001). When treatment was given after induction of pancreatitis,
      the mortality rate was 75% (P = 0.2). Administration of SMS 201-995 did not
      influence the serum concentrations of amylase markedly, but the lipase levels
      were significantly lowered (P less than 0.05). The low levels of serum insulin
      and the glucose level in whole blood were not influenced. The volume of ascitic
      fluid was reduced (P less than 0.01). Moreover, less peritoneal fat necrosis was
      seen, suggesting a reduction in toxic factors in the ascitic fluid. Treatment
      with SMS 201-995 prior to induction of pancreatitis caused a significant increase
      in the levels of circulating 6-keto-PGF1 alpha, the stable metabolite of
      prostaglandin I2 (P less than 0.01). The levels of thromboxane B2 and
      prostaglandin E2 did not change significantly. The present data support the
      hypothesis that SMS 201-995 is an activator of prostaglandin I2, thereby
      modifying the course of the disease.

PMID- 1380427
TI  - Methodology of antiemetic trials.
AB  - Progress in antiemetic research dictates that clinical trials of antiemetic
      agents be conducted according to guidelines for Good Clinical Practice, as
      follows. Studies must be of a prospective, parallel-group design in which the new
      treatment is compared with the existing best available treatment, after optimal
      dosage schedules for each have been established. Ethically, placebo-controlled
      trials can only be justified when chemotherapy with a low emetogenic potential is
      used. All end-points (nausea, vomiting, adverse events and quality of life
      parameters) must be specified in detail before the trial is begun. Patient
      populations must be homogenous with respect to prior chemotherapy and other
      confounding variables. Finally, patients must actively participate in the
      evaluation of antiemetic therapy, since only they can provide reliable
      information regarding the impact of nausea and vomiting on their quality of life.

PMID- 1380428
TI  - Tropisetron. A review of the clinical experience.
AB  - This review describes clinical experience with tropisetron, a new 5
      hydroxytryptamine type 3 (serotonin 3)-receptor antagonist, which was found to
      possess antiemetic properties in animal studies and pilot studies in chemotherapy
      treated patients. Tropisetron 5mg once daily is an effective and well tolerated
      antiemetic treatment for chemotherapy-induced emesis. Tropisetron can be
      administered without special precautions to all patients who undergo aggressive
      chemotherapy, and remains effective during multiple chemotherapy courses. The
      efficacy of tropisetron compares well with that of the best available complicated
      antiemetic cocktails, but tropisetron is better tolerated. The simple dosage
      schedule of either 1 injection or 1 capsule per day makes tropisetron ideal for
      both inpatient and outpatient treatment.

PMID- 1380429
TI  - Prevention of chemotherapy-induced nausea and emesis in patients responding
      poorly to previous antiemetic therapy. Comparing tropisetron with optimised
      standard antiemetic therapy.
AB  - In a multicentre trial, 78 patients with a variety of malignancies, who had
      experienced insufficient control of emesis (greater than or equal to 3 episodes
      within 24 hours) while receiving standard antiemetics during previous
      chemotherapy, were randomly assigned to receive tropisetron 5mg once daily for 5
      days or conventional antiemetic drugs. No attempt was made to standardise the
      conventional antiemetic treatment, which was given according to the usual
      practice of the participating institutions. Emesis was evaluated by counting
      emetic episodes and nausea by asking the patients to record on a diary chart the
      duration and severity of the nausea. Emesis was much better controlled with
      tropisetron than with standard drugs, complete control during the first 24 hours
      being achieved in 42% and 8% of patients, respectively, (p less than 0.001).
      Nausea was of significantly shorter duration (6.9 vs 10.3 hours; p less than
      0.01) and was less severe (p less than 0.005) in the tropisetron group. The
      patients' overall assessment of treatment outcome was markedly better for
      tropisetron than for the standard antiemetic therapy. The superior efficacy of
      tropisetron was especially marked during the first 24 hours. For delayed nausea,
      no significant difference between treatments was seen. No serious adverse effects
      were observed.

PMID- 1380430
TI  - Compassionate use of a 5-HT3-receptor antagonist, tropisetron, in patients
      refractory to standard antiemetic treatment.
AB  - The efficacy of tropisetron in the prevention of nausea and vomiting induced by
      chemotherapy of varying emetogenic potential was evaluated in 545 patients with a
      variety of malignancies who had either proved refractory to antiemetic treatment
      during previous chemotherapy courses or who were considered to be at high risk of
      nausea and vomiting. Tropisetron 5 or 10mg was administered intravenously just
      before chemotherapy, with the possibility of additional oral or intravenous doses
      on the day before chemotherapy and on 1 or more subsequent days. On day 1 of the
      first course of chemotherapy, a complete response (no nausea and no vomiting) was
      achieved in 62% of patients and a partial response (1 to 4 vomits and/or episodes
      of nausea) in 29%. Among the 325 patients who received a second course of
      chemotherapy, more than 80% of those with a complete response on day 1 of course
      1 also had a complete response on day 1 of course 2; 37% and 26%, respectively,
      of patients with a partial response or failure (1 or more vomits and/or episodes
      of nausea) on day 1 of course 1 then had a complete response on day 1 of course
      2.

PMID- 1380431
TI  - Tropisetron, a new 5-HT3-receptor antagonist, in the prevention of radiation
      induced nausea, vomiting and diarrhoea.
AB  - Oral tropisetron, a 5-hydroxytryptamine type 3 (serotonin3) [5-HT3]-receptor
      antagonist, at a dose of 5mg daily was evaluated as antiemetic prophylaxis during
      postoperative abdominal irradiation. 20 women with International Federation of
      Gynecology and Obstetrics (FIGO) stage I to III ovarian carcinoma were included.
      12 women received irradiation of whole abdominal fields and 8 of lower
      abdominal/pelvic fields. Efficacy and adverse events were recorded by the
      patients in diary-form booklets. The cumulative weekly incidence of patients with
      nausea, which was generally mild and of short duration, increased from 30% at the
      start of radiotherapy to 54% at the end of treatment. Episodes of vomiting
      occurred in less than 10% of the patients. Diarrhoea was common towards the end
      of the radiotherapy courses, and the proportion of patients needing extra
      antidiarrhoeal medication (loperamide) increased from 38% during the first week
      to 100% at the end of the radiotherapy course. Mean weight loss was 1.2kg during
      the 5- to 6-week course. Overall ratings for quality of life were excellent or
      good in 75 to 85% of patients. Tropisetron seems to be a promising and well
      tolerated drug in conjunction with extended radiotherapy of abdominal fields.
      This was an open study, establishing the methodology for long term follow-up of
      patients during fractionated radiotherapy.

PMID- 1380432
TI  - Three years' experience with tropisetron in the control of nausea and vomiting in
      cisplatin-treated patients.
AB  - The efficacy and tolerability of tropisetron in preventing cisplatin-induced
      nausea and vomiting was studied in 2 open trials and compared with the efficacy
      and tolerability of metoclopramide plus lorazepam in a randomised crossover
      trial. In the first study, tropisetron 10mg was administered intravenously over
      15 minutes before the cisplatin infusion and a second 10mg dose was given after
      the 60-minute infusion of cisplatin (greater than 50 mg/m2) in 54 patients with
      advanced cancers, for a total of 165 courses. Good responses for nausea and
      vomiting were recorded in 83.0% and 87.9% of courses, respectively, with complete
      protection from nausea and vomiting in 44.8% and 66.1% of courses, respectively.
      In the second study in 25 patients whose characteristics and cisplatin schedule
      were comparable with those of the first study, very similar results were achieved
      in 104 courses of chemotherapy, despite a reduction in tropisetron dose to a
      single 5mg intravenous infusion 15 minutes before cisplatin. The efficacies of
      intravenous tropisetron 5mg and metoclopramide 2 mg/kg plus lorazepam
      administered 15 minutes before cisplatin in preventing acute and delayed nausea
      and vomiting were compared in a randomised crossover study involving 20 patients.
      Tropisetron was significantly superior (p less than 0.001) in controlling both
      acute and delayed (day 1) symptoms. In all studies, the tolerability of
      tropisetron was excellent. The most frequent side effect was mild to moderate
      headache, occurring in 5 to 7% of patients. In conclusion, our experience
      suggests that tropisetron is an effective and well tolerated antiemetic drug that
      improves the quality of life of cancer patients administered highly emetogenic
      chemotherapy regimens.

PMID- 1380433
TI  - Biochemical analyses of proteolytic nicking of the human glycoprotein hormone
      alpha-subunit and its effect on conformational epitopes.
AB  - Conformational features of two epitopes on the glycoprotein hormone alpha-subunit
      were investigated using two antihuman FSH (anti-hFSH) monoclonal antibodies
      (mAbs) 3A and 5F that recognize different epitopes and are specific for alpha
      subunit. These mAbs were used to investigate whether the conformation of these
      epitopes was different in heterodimeric hFSH, hTSH, hLH, or hCG. Any differences
      in the mass of hormone in each preparation were accounted for by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis/Western blot analysis of all hormone
      preparations used in this study. Rabbit anti-hFSH alpha-(11-27) antipeptide
      antisera and [125I]protein-G were used in the Western blot analysis.
      Radioactivity associated with each band was determined and used to normalize the
      mass of alpha-subunit in each reference preparation used in the displacement
      assays. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was also
      performed in order to examine the integrity of each of the hormone reference
      preparations. hTSH alpha and, to a lesser extent, hLH alpha preparations
      contained an internal nick in the polypeptide chain. RIA analysis performed using
      heterodimeric glycoprotein hormones as competitors revealed that an average 100
      fold difference in the ED50 values for hFSH compared to the other glycoprotein
      hormones was seen with mAb 3A. Therefore, the conformation of 3A epitope appeared
      to be different in hFSH than in hTSH, hLH, or hCG. In comparison, the epitope
      recognized by mAb 5F only had an average 7-fold difference in reactivity (ED50
      values) for hFSH compared to hTSH, hLH, and hCG. Likewise, competition assays
      using the respective alpha-subunits and mAb 5F revealed a pattern of competition
      similar to that observed with heterodimers, with an average 4-fold difference in
      the ED50 values for hFSH alpha compared to those for hTSH alpha, hLH alpha, and
      hCG alpha. Therefore, the conformation of the 5F epitope appears unaffected by
      association of alpha-subunit with beta-subunit. Accordingly, any differences in
      the conformation of the four alpha-subunits, as demonstrated by these small
      differences in ED50 values, appear to be inherent to each alpha-subunit. In fact,
      the 5F epitope appears to be quite rigid, since nicked alpha-subunit preparations
      could compete with [125I]hFSH for binding to 5F with comparable potency to non
      nicked alpha-subunits. These findings support the concept that epitopes on
      heterodimeric hFSH alpha may have different conformational features. Some are
      specific for heterodimeric hFSH alpha, and we refer to these as conformationally
      active (flexible). Others are common to the four human glycoprotein hormone alpha
      subunits, suggesting that they are conformationally constrained (rigid).

PMID- 1380434
TI  - Mitogenic activity of epidermal growth factor on newborn rat astroglia:
      interaction with insulin-like growth factors.
AB  - Newborn rat astroglia cells possess epidermal growth factor (EGF) and insulin
      like growth factor (IGF) receptors, which suggests that these growth factors
      regulate their growth and development. To determine the relative roles and
      interactions between the two growth factors on astroglial growth, primary
      cultures of astroglial cells from newborn rats (1 day postnatal) were treated
      with pure peptides, singly or in combination in various concentrations, and the
      growth response was determined by DNA synthesis ([3H]thymidine incorporation).
      EGF, IGF-I, and IGF-II, as single peptides, stimulated DNA synthesis, with half
      maximal stimulatory concentrations of 0.25 ng/ml for EGF, 2.0 ng/ml for IGF-I,
      and 25 ng/ml for IGF-II, respectively. These findings indicate that astroglial
      cells are responsive to these growth factors in physiological concentrations,
      with the relative sensitivity of EGF greater than IGF greater than IGF-II. When
      EGF and IGF-I were added in combination, the growth stimulatory effect was
      greater than the additive effects of each growth factor added alone, indicating
      that the two growth factors act in synergism with each other. In particular,
      addition of increasing concentrations of EGF from 0.25-10 ng/ml to a constant
      concentration of 50 ng/ml IGF-I resulted in significant potentiation of
      [3H]thymidine incorporation of astroglial cells. To determine if the synergistic
      effect was due to a local synthesis of IGF-I by astroglia, a specific monoclonal
      antibody against IGF-I (Sm 1.2) was added to the peptides. Sm 1.2 decreased not
      only IGF-I-stimulated DNA synthesis, but also EGF-stimulated DNA synthesis,
      suggesting that the effects of EGF were contributed to in part by the local
      synthesis of IGF-I by astroglial cells. Analysis of conditioned medium from cells
      treated with EGF revealed a significant increase (approximately 2-fold) in IGF-I
      (from 4.5 to 8.8 ng/ml), but not IGF-II. To determine if the EGF effect on IGF
      synthesis was at the level of IGF-I mRNA transcription, stable IGF-I mRNA levels
      were determined in the astroglial cells before and after stimulation with EGF,
      using Northern analysis and quantification by densitometry. Astroglia expressed
      four IGF-I mRNA transcripts as in the adult and fetal liver, but only one (3.6
      kilobases) IGF-II mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380435
TI  - Diverse effects of tachykinins on luteinizing hormone release in male rats:
      mechanism of action.
AB  - The tachykinins are a group of structurally related peptides found in the rat
      hypothalamus and anterior pituitary. We have evaluated the effects of four
      tachykinins on LH release in male rats. In intact male rats,
      intracerebroventricular (icv) injection of neurokinin A (NKA), neuropeptide K
      (NPK), and neuropeptide-gamma (NP gamma) elicited dose-related, transient
      increases in plasma LH. Substance P (SP) was ineffective under these conditions.
      A further examination showed that in vitro incubation with either NPK or NP gamma
      of hemipituitaries from intact but not castrated male rats promoted release of LH
      into the medium, thereby revealing that the excitatory effects of tachykinins in
      intact male rats may, in part, be a result of stimulation of LH release directly
      from the anterior pituitary. On the other hand, the effects of these four
      tachykinins on LH release were different in castrated rats.
      Intracerebroventricular injection of NPK, NKA, and NP gamma as well as SP, which
      was ineffective in intact male rats, evoked a long-lasting suppression of LH
      release. Comparatively, NPK was the most effective tachykinin in eliciting LH
      responses in both of these tests involving different endocrine environments. We
      next evaluated the possibility that the inhibitory effects of tachykinins (NPK)
      may be mediated by activation of inhibitory endogenous opioid peptides. The
      results showed that iv infusion of the opiate receptor antagonist naloxone, to
      block the possible inhibitory effects of endogenous opioid peptides, only
      partially counteracted the suppressive effects of icv NPK on plasma LH levels.
      Thus, in addition to revealing the diverse effects of structurally related
      tachykinins on LH release, the results of these investigations showed
      specifically that the NK-2 receptor agonists NPK, NP gamma, and NKA stimulated LH
      release in intact rats, in part, by a direct action at the level of the
      pituitary, whereas the NK-1 receptor agonist SP was inactive under these
      conditions. These findings imply a paracrine/autocrine mode of excitatory action
      on LH release involving pituitary NK-2 receptor subtypes. On the other hand, in
      castrated rats, all four tachykinins readily suppressed LH release by a central
      action involving, in part, an activation of hypothalamic opioid systems.

PMID- 1380436
TI  - Effect of follicle-stimulating hormone on insulin-like growth factor-I-stimulated
      rat granulosa cell deoxyribonucleic acid synthesis.
AB  - Granulosa cells from diethylstilbestrol-treated immature rats were cultured in a
      defined medium on collagen-coated plates. Thymidine incorporation was
      significantly increased by insulin (ED50, 656 +/- 110 ng/ml) and insulin-like
      growth factor (IGF-I; ED50, 95 +/- 10 ng/ml). Insulin and IGF-I stimulations were
      amplified by methylisobutylxanthine an inhibitor of phosphodiesterase activity.
      The effect of both peptides were also enhanced by low doses of (Bu)2cAMP (0.2-1
      mM). In contrast, higher concentrations were inhibitory. Similarly, FSH produced
      a biphasic enhancement of the insulin- and IGF-I-stimulated DNA synthesis.
      Maximal effects (2- to 6-fold increases) were observed with the lower doses (2-20
      ng/ml) of the gonadotropin. FSH enhancement of IGF-I-stimulated DNA synthesis was
      dependent on cell density. Plating densities of 3-5 x 10(5) cells/cm2 were
      required for a maximal interaction. It is concluded that FSH, acting through a
      cAMP-mediated pathway, may regulate granulosa cell proliferation by modulating
      the mitogenic effects of insulin and/or IGF-I.

PMID- 1380437
TI  - Insulin-like growth factor-II and its binding proteins in placental development.
AB  - To identify potential mediators or modulators of insulin-like growth factor-II
      (IGF-II) action in the placenta, we used in situ hybridization to map patterns of
      gene expression for IGF-II, the functionally related IGF-binding proteins
      (IGFBPs) 1-4, and the type 1 and 2 IGF receptors in developing rat and term human
      placentas. IGF-II mRNA was highly abundant in trophoblast-derived elements of the
      rat placenta from implantation to maturity, except for a significant local
      reduction in IGF-II gene expression in the junctional zone just before term.
      IGFBP2 mRNA was barely detected during early placental development, but increased
      significantly toward term and was most abundant in the junctional zone. The basal
      plate of the term human placenta showed a similar pattern, with a superficial
      layer of cytotrophoblasts containing IGF-II mRNA anatomically apposed to a deeper
      layer of cells expressing IGFBP2 mRNA. Placental IGFBP1, -3, and -4 mRNAs were
      much less abundant than IGFBP2 and were restricted to the yolk sac and
      vasculature. Type 1 and 2 IGF receptor mRNAs were abundant and shared the same
      distribution, together with IGF-II, in the labyrinthine zone. These findings
      suggest that IGFBP2 may be an important modulator of IGF-II action in placental
      development. Furthermore, the colocalization of both types of IGF receptor mRNA
      supports the view that these receptors may compete for IGF-II binding in the
      placenta.

PMID- 1380438
TI  - Phosphorylation of the rodent negative acute-phase protein alpha 1-inhibitor-III
      by the insulin receptor tyrosine kinase.
AB  - alpha 1-Inhibitor-III (alpha 1I3), a broad range proteinase inhibitor, member of
      the alpha-macroglobulin family, is abundant in normal rat plasma. Insulin
      dependent tyrosine phosphorylation of a monomeric 195K glycoprotein (pp195) was
      observed in wheatgerm agglutinin (WGA)-Sepharose-purified insulin receptor
      preparations from rat liver and muscle. Phosphorylation of pp195 in vitro
      required a basic poly-amino acid, i.e. poly-L-lysine. We present evidence
      identifying pp195 as alpha 1I3. In situ perfusion with saline essentially removed
      pp195 from rat livers. Addition of normal rat plasma to liver homogenates or to
      WGA eluates restored insulin-stimulated phosphorylation of pp195; plasma from
      streptozotocin-diabetic rats was much less effective. Liver-derived pp195
      copurified with an abundant plasma protein, with the characteristics of alpha
      1I3, on size exclusion and ion-exchange chromatography. An approximately 195K
      protein, comigrating with alpha 1I3, was markedly diminished in plasma from
      diabetic rats, and alpha 1I3 concentration was decreased by approximately 70%
      upon immunoblot analysis. Highly purified alpha 1I3 was phosphorylated by muscle-
      or liver-derived insulin receptors in the presence of 1 microM poly-L-lysine and
      comigrated with pp195 on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. alpha 1I3 phosphorylation was half-maximal at approximately 70
      nM and was stimulated by insulin 7-fold. Hindlimb perfusion removed more than 90%
      plasma albumin but only approximately 20% pp195 from muscles. alpha 1I3 messenger
      RNA was identified in liver but not in muscle. A specific antibody against alpha
      1I3 immunoprecipitated phosphorylated pp195 in WGA-purified insulin receptor
      preparations from nonperfused liver and from saline perfused and nonperfused
      muscle. alpha 1I3 is bound and internalized by alpha-macroglobulin receptors;
      whether it is phosphorylated in vivo is unknown. Hepatic alpha 1I3 synthesis may
      diminish in diabetic rats.

PMID- 1380439
TI  - Alpha 2-macroglobulin expression in the mesometrial decidua and its regulation by
      decidual luteotropin and prolactin.
AB  - During decidualization, cells of the endometrium grow and differentiate giving
      rise to two different decidual tissues located in either the antimesometrial or
      mesometrial site of the uterus in the rat. These tissues have different functions
      in pregnancy. The antimesometrial decidua is an endocrine gland that secretes
      hormones, whereas the mesometrial decidua appears to play an important role in
      limiting trophoblast invasion. Since the decidual tissue of the rat produces
      alpha 2-macroglobulin (alpha 2MG), we examined whether this potent protease
      inhibitor is specifically expressed by the mesometrial tissue, the site of
      trophoblast invasion, and whether the alph 2MG gene is regulated by decidual
      luteotropin (DLt), the PRL-like hormone secreted by the neighboring
      antimesometrial cells. To determine the secretory proteins of the rat decidua,
      antimesometrial and mesometrial tissues were dissected out from pseudopregnant
      rats and cultured with [35S]methionine. The major protein secreted by the
      antimesometrial cell was the 29-kilodalton decidual luteotropin, whereas a 180
      kilodalton protein was predominantly secreted by the mesometrial tissue.
      Immunoprecipitation studies of 35S-radiolabeled proteins revealed that this high
      mol wt protein is alpha 2MG and that it is secreted exclusively by the cells
      forming the mesometrial tissue. To examine whether the alpha 2MG gene was also
      expressed specifically in the mesometrial decidua, total RNA was isolated from
      both mesometrial and antimesometrial tissues of day 9-12 pseudopregnant rats and
      hybridized with alpha 2MG cDNA. Northern blot analysis revealed a 5.4-kilobase
      message, which was abundantly expressed in the mesometrial decidua. Little, if
      any, alpha 2MG mRNA was detected in antimesometrial decidua. The ontogeny of the
      message in the decidua correlated well with the development of the mesometrial
      tissue. To examine whether alpha 2MG expression is regulated by DLt and/or PRL, a
      highly specific polyclonal antibody to DLt was generated and decidual tissues
      were cultured in the presence or absence of DLt antibodies with or without PRL.
      Neutralization of DLt caused a marked decrease in alpha 2MG mRNA levels. This
      down-regulation was totally reversed by the addition of PRL and was not affected
      by alpha 2MG antibodies. In summary, the results of this investigation revealed a
      compartmentalized gene expression, synthesis and secretion of alpha 2MG in the
      decidua. The secretion of this protease inhibitor, specifically by the
      mesometrial tissue which is the site of trophoblast invasion, may be the reason
      for the minimal amount of tissue damage that occurs during placentation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1380440
TI  - Cytoplasmic estrogen receptors in rat brain: immunocytochemical evidence using
      three antibodies with distinct epitopes.
AB  - The existence of cytoplasmic estrogen receptors (ERs) has been reported in the
      guinea pig brain using immunocytochemical techniques. While cytoplasmic ERs have
      been reported recently in other species, such as opossum, musk shrew, and
      ferrets, an exclusively cell nuclear pattern of ER immunoreactivity has been
      reported in the rat brain. Because all studies that have reported the existence
      of cytoplasmic ERs in the brain have used the H 222 monoclonal antibody, the
      possibility exists that this observation is idiosyncratic to this antibody. In
      the present experiment three antibodies directed against diverse epitopes on the
      ER protein were used to immunocytochemically stain ERs in rat brain. With each
      antibody, ER immunoreactivity was observed in the hypothalamus, preoptic area,
      amygdala, and midbrain periaqueductal gray. In all cases we observed the highest
      density of reaction product in cell nuclei, but extensive cytoplasmic
      immunostaining was observed in most areas as well. In addition to demonstrating
      the existence of neural ER immunoreactivity in perikaryal cytoplasm and
      cytoplasmic processes in the brain, this study suggests that the neural
      cytoplasmic ER immunoreactivity is not just a small fragment of the receptor
      protein; rather, it is likely to be the entire receptor.

PMID- 1380441
TI  - Secretion of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 by
      intestinal epithelial (IEC-6) cells: implications for autocrine growth
      regulation.
AB  - To identify the factors regulating the proliferation of intestinal epithelium, we
      examined the effects of various growth factors on [3H] thymidine incorporation
      into the DNA of IEC-6 cells, an intestinal epithelial cell line derived from rat
      jejunal crypts. Insulin-like growth factor-I (IGF-I), IGF-II, and insulin
      stimulated the DNA and protein synthesis of IEC-6 cells in serum-free medium
      supplemented with transferrin, dexamethasone, and BSA (basal medium).
      Concentration-response experiments demonstrated that IGF-I is approximately 10
      times more potent than IGF-II or insulin in producing 2- to 3-fold stimulations
      of DNA and protein synthesis by IEC-6 cells. In addition, IEC-6 cells
      proliferated slowly in the basal medium without any added growth factors.
      Analysis of medium conditioned by IEC-6 cells by gel filtration chromatography,
      RIA, HPLC, and N-terminal sequencing revealed that IEC-6 cells synthesize and
      secrete mature, 7,500 mo wt (M(r)) IGF-II as well as high M(r) forms of IGF-II.
      In addition, ligand blot, immunoblot, and N-terminal sequence analyses showed
      that IEC-6 cells produce the 34,000 M(r) IGF-binding protein-2 (IGFBP-2). To
      determine if IGFBP-2 modulates IGF responses in IEC-6 cells, the IGF-I analogs,
      Des-(1-3)-IGF-I and [Gln3,Ala4,Tyr15,Leu16]IGF-I, both of which have a reduced
      affinity for IGFBPs, were tested for their effects on IEC-6 cell proliferation.
      Both analogs exhibited 10-fold greater potency than IGF-I, presumably because
      endogenously secreted IGFBPs depress IGF-I binding to cell surface receptors.
      Finally, purified IGFBP-2 attenuated the DNA synthesis of IEC-6 cells in a dose
      dependent manner. We conclude that IGFBP-2 secreted by intestinal epithelial
      cells is capable of limiting the mitogenic activity of both exogenous and
      endogenous IGFs by blocking the association of the growth factors with cell
      surface binding sites. These results further suggest that the growth of IEC-6
      cells is modulated by autocrine mechanisms involving IGF-II and IGFBP-2.

PMID- 1380442
TI  - Arginine vasopressin stimulates atrial natriuretic peptide gene expression and
      secretion from rat diencephalic neurons.
AB  - The central nervous system modulates cardiovascular function and fluid and
      electrolyte balance in part through the actions of vasoactive
      peptides/neurotransmitters. The presence of several vasoactive peptides and their
      receptors in the hypothalamus suggests a possible interaction at this site. One
      level at which vasoactive peptides such as arginine vasopressin (AVP) and atrial
      natriuretic peptide (ANP) might interact is through the mutual regulation of
      production and secretion in the hypothalamus. To determine whether AVP modulates
      ANP gene expression and secretion, we cultured fetal rat diencephalic neurons in
      the presence of AVP. AVP induced a significant increase in ANP secretion in dose
      related fashion (mean +/- SEM basal ANP, 87 +/- 4 pg/ml; maximal mean AVP
      stimulated ANP, 146 +/- 6 pg/ml; P less than 0.05, by analysis of variance).
      Neither oxytocin nor the vasoactive neuropeptide angiotensin-II had any effect on
      ANP secretion. The stimulatory effect of AVP was significantly blocked by
      coincubation with a V1 receptor antagonist, but was unaffected by a V2 receptor
      antagonist. The immunoreactive ANP secreted in response to AVP was the major
      brain isoform, ANP-(103-126). Coincubation with a calcium channel antagonist,
      nifedipine, had no effect on AVP-induced ANP secretion, while ryanodine, an
      inhibitor of intracellular calcium mobilization, significantly reduced the
      stimulatory effect of AVP. AVP induced a dose-related, nearly 3-fold maximal
      increase in ANP mRNA expression at 4 h. Coincubation of the neurons with a V1
      receptor antagonist also significantly attenuated the increased ANP gene
      expression induced by AVP. These results indicate that AVP acts directly through
      V1 receptors on cultured fetal rat diencephalic neurons to augment ANP gene
      expression and secretion of the peptide. The effects are probably related to AVP
      stimulated mobilization of intracellular calcium and not the result of calcium
      influx into the cell. These studies provide the first evidence that AVP modulates
      ANP production from cultured neurons. In the central nervous system, these two
      vasoactive neuropeptides might interact in part through the regulation of ANP
      production by AVP.

PMID- 1380443
TI  - Insulin-like growth factor binding protein expression in the hypothyroid rat is
      age dependent.
AB  - Thyroid hormone is essential for normal growth and development. For certain T4
      effects, there is a critical period during ontogeny when normal T4 levels are
      required, and thyroid replacement after that period cannot correct the changes in
      hypothyroid animals. We have previously described a prolonged high expression of
      serum insulin-like growth factor binding protein (IGFBP)-2 during the perinatal
      period in congenitally hypothyroid rats. To see if this effect was confined only
      to a certain period during rat ontogeny, we made rats hypothyroid with
      methimazole treatment either prenatally, or at different postnatal ages from 1 to
      14 days of life, and at adult age. Serum IGF-I levels were reduced by
      approximately 30% in all the 18-day-old hypothyroid animals, and did not
      correlate with the duration of the hypothyroid state. Serum IGF-I levels in the
      adult animals were 50% of control levels. At the age of 18 days, control animals
      had only very low levels of IGFBP-2 demonstrable by western ligand blotting,
      whereas the congenitally hypothyroid animals had elevated levels. Pups placed on
      methimazole treatment since the first day of life showed higher IGFBP-2 levels at
      the age of 18 days, although the change was not as prominent as in the
      congenitally hypothyroid animals (200% vs. 500% of control levels, respectively).
      Binding protein changes were approximately 2-fold at the mRNA level. Rats started
      on methimazole after the first 5 days of life showed normal low levels of IGFBP-2
      at the age of 18 days. Abnormal IGBFP-2 expression in congenitally or neonatally
      hypothyroid animals could be corrected by thyroid hormone replacement, if started
      during the first week of the life, but not later. In adult hypothyroid animals,
      there was no induction of IGFBP-2 expression, but the levels of IGFBP-3 and -4
      were decreased to 80% and to 30% of control levels, respectively. IGFBP-3
      messenger RNA (mRNA) levels were decreased to 50% of control levels but IGFBP-4
      mRNA levels were paradoxically increased in the hypothyroid animals. All these
      changes could be corrected by T4 replacement. In conclusion, there exists a
      critical period during the perinatal development of the rat, when thyroid hormone
      is essential for a subsequent normal IGFBP-2 ontogenic pattern. Adult animals
      show a completely different IGFBP response to hypothyroidism, with a decrease of
      IGFBP-3 and -4 levels. Thus, the effects of thyroid hormone on IGF-IGFBP axis
      regulation depend on the developmental stage of the animal.

PMID- 1380444
TI  - Spatio-temporal expression of estrogen sulfotransferase within the hepatic lobule
      of male rats: implication of in situ estrogen inactivation in androgen action.
AB  - Estrogen sulfotransferase (EST) catalyzes transfer of the sulfate group from
      phosphoadenosine phosphosulfate to estrogenic steroids. Since estrogen sulfates
      do not bind to the estrogen receptor with high affinity, EST can control the
      intracellular level of the receptor-active estrogens. Androgen action in the rat
      liver, as indicated by the androgenic induction of alpha 2u-globulin, is
      inhibited by low levels of estrogens. Thus, in situ estrogen inactivation by EST
      is expected to increase hepatic androgen sensitivity. During the lifespan of the
      animal, rat liver undergoes three distinct phases of androgen sensitivity, i.e.
      prepubertal androgen insensitivity, androgen sensitivity after approximately 40
      days of age, and androgen insensitivity during senescence (greater than 750
      days). EST in the liver is expressed only after puberty, when the liver becomes
      androgen sensitive. Furthermore, localization of EST and its corresponding mRNA
      within the lobular unit of the liver demonstrates that only androgen-responsive
      hepatocytes located around the central vein contain immunoreactive EST and its
      corresponding mRNA. These temporal and spatial correlations of EST expression and
      hepatic androgen sensitivity support the concept that steroid-inactivating
      enzymes play important roles in sex hormone action.

PMID- 1380445
TI  - Inhibition of human fibroblast insulin-like growth factors binding protein
      (IGFBP) production by IGFBP-3.
AB  - Human neonatal fibroblasts in monolayer culture secrete a number of insulin-like
      growth factor binding proteins (IGFBPs), including IGFBP-3, which may alter
      paracrine or autocrine IGF activity. Studies in vitro have demonstrated that
      exogenous IGFBP-3 can both inhibit and potentiate IGF action in these cells;
      however, it is not known to what extent there is regulatory interaction between
      the IGFBPs. In this study we report that exogenous and endogenous IGFBP-3 inhibit
      production of an IGF inducible IGFBP. When analyzed by SDS-PAGE and [125I]IGF-II
      ligand blotting, human neonatal fibroblasts secrete IGFBP-3, an IGFBP of 29-31
      kDa, and a 22-24 kDa IGFBP after treatment with 50 ng/ml IGF-I. When IGF-I
      treatment was carried out in the presence of increasing concentrations (50-1000
      ng/ml) of pure human serum-derived IGFBP-3, there was a dose-dependent decrease
      in the 29-31 kDa protein. In the presence of excess (250 ng/ml) IGF-I, IGFBP-3
      had approximately 20-fold reduced potency in inhibiting 29-31 kDa IGFBP. When
      endogenous production of IGFBP-3 was increased by treatment with transforming
      growth factor-beta 1 (TGF beta 1), there was complete inhibition of 29-31 kDa
      IGFBP, while at high IGF-I concentrations TGF beta 1 had 2 to 3-fold reduced
      potency. These results demonstrate that fibroblast IGFBP production can be
      altered by exogenous and endogenous IGFBP-3, and suggest the existence of
      regulatory interactions between fibroblast IGFBPs.

PMID- 1380446
TI  - Implantation of self-expanding esophageal metal stents for palliation of
      malignant dysphagia.
AB  - Eleven self-expanding metal stents were perorally implanted in ten patients with
      locally advanced malignant obstruction of the esophagus. After bougienage of the
      strictures, the stents were painlessly inserted and properly released by means of
      an 18 French gauge delivery catheter. In all cases, the endoprostheses expanded
      to a diameter of 14-20 mm and achieved immediate improvement of dysphagia. One
      perforation was seen after a single session of dilatation and subsequent stent
      insertion. No other early complication was observed. After a median follow-up of
      74 days (Range, 33-252 days), one of eight patients is still alive and 7 died of
      non-procedural causes. The grade of dysphagia improved from a mean of 2.9 to a
      mean of 1.6 and 2.0, respectively, depending on the follow-up period (scale 0-4).
      Esophageal reobstruction occurred in four patients due to food impaction (two
      patients) or tumor ingrowth into the stent through the wire mesh (two patients).
      Recanalisation of the obstructed stent lumen was achieved by endoscopic
      irrigation (two patients), laser therapy only (one patient) or diathermia with
      subsequent insertion of a conventional plastic endoprosthesis into the metal
      stent (one patient). The initial results are promising. The delivery system, the
      wide-bore diameter, the macroporous configuration and the low mass of the self
      expanding stents would seem to be associated with a less traumatic insertion
      procedure and a lower rate of stent migration as compared with conventional
      prostheses. Technical improvement may be required for prevention of tumor
      infiltration. Controlled trials are warranted to determine the future role of
      metallic stents for palliation of esophagocardial tumors.

PMID- 1380447
TI  - Self-expanding metal stents for palliation of malignant esophageal obstruction--a
      pilot study of eight patients.
AB  - We sought to determine whether the application of a self-expanding metal stent
      enables palliation of malignant dysphagia with minimal risk. The results of pilot
      studies from two centers are reported. We treated 8 inoperable patients with a 14
      mm self-expanding metal stent (Wallstent). The stent was applied without general
      anesthesia under mild i.v. sedation. The procedure was successful in all cases.
      No side effects were noted. In one patient, tumor ingrowth through the meshes of
      the stent occurred. This patient was additionally treated with a percutaneous
      gastrostomy. One patient experienced tumor overgrowth of the proximal end,
      necessitating laser treatment. Three patients were still alive after three
      months. The mean number of cumulative endoscopic interventions per patient was
      2.2 (SD: +/- 2; median 2). The mean observation time was 10.7 weeks +/- 2 (median
      12). Dysphagia was graded from 0 (normal swallowing) to 4 (inability to swallow
      saliva). Dysphagia was significantly (p less than 0.0005) reduced from grade 3.1
      (SD: +/- 0.35) to 0.5 (SD: +/- 0.5) immediately after stenting. 62.5% of the
      patients were able to manage a virtually normal diet (in one of these patients
      dysphagia recurred six weeks after stent placement due to tumor ingrowth). Six
      patients (75%) were able to ingest all necessary calories orally. The application
      of a 14 mm self-expanding metal stent in cases of inoperable malignant esophageal
      obstruction seems to offer safe and effective palliation of malignant dysphagia.

PMID- 1380448
TI  - Self-expanding metal stents for palliation of malignant gastric outlet
      obstruction.
AB  - Treatment of inoperable gastric outlet obstruction caused by tumor compression is
      difficult and often unsatisfactory. The case of a 56-year-old female patient in
      whom self-expanding stents were implanted, successfully enabling oral nutrition,
      is reported.

PMID- 1380449
TI  - Analysis of human tear proteins by two-dimensional electrophoresis.
AB  - Human tear proteins in the conjunctival sac were separated on the basis of the
      differences in their isoelectric points and molecular weights using micro two
      dimensional electrophoresis combined with immunoblotting. The two-dimensional
      electrophoretic patterns of tear proteins from patients with conjunctivitis were
      compared with those from normal individuals. We also measured integrated
      intensities of seven protein spots, lactoferrin (LF), albumin and five specific
      tear proteins (STP), to examine differences in the amounts of these proteins in
      tears from normal individuals of different sexes. In the tears from patients with
      conjunctivitis, secretory immunoglobulin A (IgA), LF and STP spots were stained
      more weakly, whereas the albumin spot was stained more strongly as compared with
      those from normal individuals. Furthermore, haptoglobin and IgG spots appeared in
      the tears from patients with conjunctivitis. These were more prominent in the
      tears from patients with severe conjunctivitis. There were significant
      differences in the amounts of LF and two kinds of STPs in the different sexes.
      The amounts of these proteins were larger in females.

PMID- 1380450
TI  - Specific polypeptide markers in chronic B cell malignancies detected by two
      dimensional gel electrophoresis.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analysis of silver
      stained polypeptides was used to discriminate the cell protein profiles in
      chronic B cell malignancies. We identified 5 distinct polypeptides (H1 to H5)
      present in hairy cell leukemia (HCL) (14 cases) and absent in most chronic
      lymphocytic leukemia (CLL) and normal B lymphocytes. Two polypeptides, H2 and H5,
      were absolutely specific of HCL. The 2-D PAGE profiles found in 3 splenic
      lymphoma with villous lymphocytes (SLVL) and 2 HCL variants (HCL-V) were similar
      to HCL with a unique additional peptide present in 3/3 SLVL and 1/2 HCL-V. When
      HCL and SLVL were assessed for the CLL stage-specific 2-D PAGE patterns, HCL was
      related to stage A/B while SLVL was related to stage C. In conclusion, 2-D PAGE
      analysis of the molecular pattern of B lymphocytes provides a new means to
      recognize the leukemic origin of the sample and distinguish HCL from CLL and
      SLVL.

PMID- 1380451
TI  - Molecular architecture of acetylcholinesterase collagen-tailed forms;
      construction of a glycolipid-tailed tetramer.
AB  - Asymmetric forms of Torpedo acetylcholinesterase (AChE) are produced in COS cells
      by the simultaneous expression of collagenic subunits (Q) and catalytic T
      subunits (AChET). Truncated AChET delta subunits, from which most of the C
      terminal peptide (TC) had been deleted by mutagenesis, did not associate with Q
      subunits. The TC peptide is therefore necessary for the association of the AChET
      and Q subunits. In order to determine the orientation of the Q subunit in the
      collagen-tailed forms, we have developed an antiserum against its non-collagenic
      C-terminal domain, expressed as a fusion protein in Escherichia coli. This
      antiserum, which recognized the Q subunit in Western blots, was found to react
      with intact asymmetric forms, but not with collagenase-treated forms, from which
      the distal part of the tail had been cleaved, suggesting that the N-terminal non
      collogenic domain (QN) is responsible for the interaction with the AChET
      subunits. This was confirmed by creating a chimeric subunit (QN/HC), in which QN
      was linked to the C-terminal peptide of the H subunit of Torpedo AChE, which
      contains the glycophosphatidylinositol (GPI) cleavage/attachment signal: co
      expression of AChET and QN/NC produced GPI-anchored tetramers, which were
      sensitive to PI-PLC and largely exposed to the external surface of the cells. We
      thus demonstrate that: (i) the HC peptide is sufficient to determine the addition
      of a glycolipid anchor and (ii) the QN domain is sufficient to bind a catalytic
      AChET tetramer by interacting with the TC peptide.

PMID- 1380452
TI  - Interaction of the RNA-binding domain of the hnRNP C proteins with RNA.
AB  - The hnRNP C proteins are among the most abundant and avid pre-mRNA-binding
      proteins and they contain a consensus sequence RNA-binding domain (RBD) that is
      found in a large number of RNA-binding proteins. The interaction of the RBD of
      the hnRNP C proteins with an RNA oligonucleotide [r(U)8] was monitored by nuclear
      magnetic resonance (NMR). 15N and 13C/15N-labelled hnRNP C protein RBD was mixed
      with r(U)8 and one- and two-dimensional (1D and 2D) NMR spectra were recorded in
      a titration experiment. NMR studies of the uncomplexed 93 amino acid hnRNP C RBD
      (Wittekind et al., 1992) have shown that it has a compact folded structure (beta
      alpha beta beta alpha beta), which is typical for the RBD of this family of
      proteins and which is comprised of a four-stranded antiparallel beta-sheet, two
      alpha-helices and relatively unstructured amino- and carboxy-terminal regions.
      Sequential assignments of the polypeptide main-chain atoms of the hnRNP C RBD
      r(U)8 complex revealed that these typical structural features are maintained in
      the complex, but significant perturbations of the chemical shifts of amide group
      atoms occur in a large number of residues. Most of these residues are in the beta
      sheet region and especially in the terminal regions of the RBD. In contrast;
      chemical shifts of the residues of the well conserved alpha-helices, with the
      exception of Lys30, are not significantly perturbed. These observations localize
      the candidate residues of the RBD that are involved in the interaction with the
      RNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380453
TI  - Monoclonal antibodies to NF-Y define its function in MHC class II and albumin
      gene transcription.
AB  - NF-Y is a sequence-specific DNA-binding protein which, as a heterodimer,
      recognizes CCAAT motifs in a variety of transcriptional promoters. We have
      generated a panel of monoclonal and affinity-purified polyclonal antibodies
      directed against various epitopes of NF-Y. These reagents are highly specific for
      either of the A or B subunits; we have mapped the epitopes recognized by the
      monoclonal antibodies to the glutamine-rich activation domain of NF-YA. The
      antibodies inhibit in vitro transcription from the promoters of the albumin gene
      and of Ea, a class II gene of the major histocompatibility complex. These data
      definitively demonstrate the role of NF-Y in regulating the transcription of two
      tissue-specific genes whose expression patterns do not overlap. Interestingly,
      the antibodies cannot inhibit a formed pre-initiation complex, but do block
      reinitiation of subsequent rounds of transcription from the same templates.

PMID- 1380455
TI  - Hepadnaviral assembly is initiated by polymerase binding to the encapsidation
      signal in the viral RNA genome.
AB  - Hepadnaviruses, as well as other pararetroviruses, express their pol (P) gene
      product unfused to the preceding core gene implying that these retroelements have
      developed a mechanism for initiating assembly and replication that is principally
      different from the one used by retroviruses and retrotransposons. We have
      analysed this mechanism for the human hepatitis B virus by using a newly
      developed, highly sensitive detection method based upon radiolabelling of the P
      protein at newly introduced target sites for protein kinase A. The results
      obtained demonstrate that polymerase encapsidation depends on the concomittant
      encapsidation of the HBV RNA pregenome and that packaging of the viral RNA, in
      turn, depends on the presence of P protein. Loss of P protein encapsidation by
      mutations inactivating the HBV RNA encapsidation signal epsilon could be
      compensated by trans-complementation with recombinant RNA molecules carrying the
      epsilon sequence. Thus, in contrast to retroviral replication, the interaction of
      the hepadnaviral P protein and the RNA genome at its packaging signal appears to
      be crucial for initiating the formation of replication-competent nucleocapsids.
      Furthermore, RNA control of P protein packaging stringently limits the number of
      polymerase molecules that can be encapsidated.

PMID- 1380457
TI  - Effects of Captan on DNA and DNA metabolic processes in human diploid
      fibroblasts.
AB  - The fungicide Captan has been examined for its effects on DNA and DNA processing
      in order to better understand the genotoxicity associated with this agent. Captan
      treatment resulted in production of DNA single strand breaks and DNA-protein
      cross-links and elicited an excision repair response in human diploid
      fibroblasts. Captan was also shown to inhibit cellular DNA synthesis and to form
      stable adducts in herring sperm and human cellular DNA. Misincorporation of
      nucleotides into Captan-treated synthetic DNA templates was significantly
      elevated in an in vitro assay using E. coli DNA polymerase I, suggesting that DNA
      adduct formation by Captan could have mutagenic consequences. In sum, these
      studies demonstrate that Captan is capable of interacting with DNA at a number of
      levels and that these interactions could provide the basis for Captan's
      genotoxicity. The extreme cytotoxicity of this fungicide, however, could be due
      to other cellular effects since at the IC50 for cell killing, approximately 0.8
      microM, none of the above genotoxic events could be detected by the methods
      employed.

PMID- 1380456
TI  - Phosphatidylinositol 3'-kinase is activated by association with IRS-1 during
      insulin stimulation.
AB  - IRS-1 undergoes rapid tyrosine phosphorylation during insulin stimulation and
      forms a stable complex containing the 85 kDa subunit (p85) of the
      phosphatidylinositol (PtdIns) 3'-kinase, but p85 is not tyrosyl phosphorylated.
      IRS-1 contains nine tyrosine phosphorylation sites in YXXM (Tyr-Xxx-Xxx-Met)
      motifs. Formation of the IRS-1-PtdIns 3'-kinase complex in vitro is inhibited by
      synthetic peptides containing phosphorylated YXXM motifs, suggesting that the
      binding of PtdIns 3'-kinase to IRS-1 is mediated through the SH2 (src homology-2)
      domains of p85. Furthermore, overexpression of IRS-1 potentiates the activation
      of PtdIns 3-kinase in insulin-stimulated cells, and tyrosyl phosphorylated IRS-1
      or peptides containing phosphorylated YXXM motifs activate PtdIns 3'-kinase in
      vitro. We conclude that the binding of tyrosyl phosphorylated IRS-1 to the SH2
      domains of p85 is the critical step that activates PtdIns 3'-kinase during
      insulin stimulation.

PMID- 1380454
TI  - Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair
      enzyme.
AB  - The DNA binding activity of Fos and Jun is regulated in vitro by a post
      translational mechanism involving reduction-oxidation. Redox regulation occurs
      through a conserved cysteine residue located in the DNA binding domain of Fos and
      Jun. Reduction of this residue by chemical reducing agents or by a ubiquitous
      nuclear redox factor (Ref-1) recently purified from Hela cells, stimulates AP-1
      DNA binding activity in vitro, whereas oxidation or chemical modification of the
      cysteine has an inhibitory effect on DNA binding activity. Here we demonstrate
      that the protein product of the ref-1 gene stimulates the DNA binding activity of
      Fos-Jun heterodimers, Jun-Jun homodimers and Hela cell AP-1 proteins as well as
      that of several other transcription factors including NF-kappa B, Myb and members
      of the ATF/CREB family. Furthermore, immunodepletion analysis indicates that Ref
      1 is the major AP-1 redox activity in Hela nuclear extracts. Interestingly, Ref-1
      is a bifunctional protein; it also possesses an apurinic/apyrimidinic (AP)
      endonuclease DNA repair activity. However, the redox and DNA repair activities of
      Ref-1 can, in part, be distinguished biochemically. This study suggests a novel
      link between transcription factor regulation, oxidative signalling and DNA repair
      processes in higher eukaryotes.

PMID- 1380458
TI  - Mutations causing defective splicing in the human hprt gene.
AB  - Ten intron mutations and one exon mutation giving rise to defective splicing in
      the human gene for hypoxanthine phosphoribosyl transferase (hprt) in T
      lymphocytes have been characterized. The splicing mutants were detected by PCR
      amplification of hprt cDNA and direct sequencing. Nine of the mutants showed
      skipping of whole exons or parts of exons in the cDNA, one mutant had an
      inclusion of an intron sequence into the cDNA, and one mutant showed both
      inclusion of an intron sequence and skipping of exons as well as a normal cDNA.
      Genomic PCR and direct sequencing of the splice sites involved showed one
      deletion of three base pairs and 10 different single base alterations to be
      responsible for these splice alterations. One mutation in the last base pair of
      exon 6 causing skipping of the entire exon 6 was found, whereas an identical
      mutation in the last base pair of exon 2 caused no aberrant splicing. It was also
      found that a deletion mutation in the pyrimidine rich stretch of the acceptor
      site of intron 7 caused skipping of the entire exon 8, whereas a base
      substitution in the last base of intron 7 caused exclusion of only the first 21
      base pairs of exon 8 as a result of the activation of a cryptic acceptor site in
      exon 8. The results show that many different types of mutations at several
      different sites can cause splicing errors in the hprt gene and that the sequence
      differences between the splice sites influence the possible spectrum of mutations
      in each site.

PMID- 1380460
TI  - Assessment of new immunosuppressive drugs in a rat cardiac allograft heterotopic
      model.
AB  - We assessed FK506 (FK) and rapamycin (RPM) in a heterotopic abdominal rat heart
      transplant model using a major histocompatibility mismatch (DA to LEW). The end
      point of our study was histologic grading of rejection (Billingham and working
      formulation) at 1 week. Two doses of FK (2.0 and 8.0 mg/kg p.o., q.d.) and RPM
      (1.5 and 6.0 mg/kg i.p., q.d.) were compared to allografts without and with
      ciclosporin (12.5 mg/kg p.o., q.d.) treatment. Results show: (1) weak heartbeat
      and full rejection on day 5 in all untreated allografts; (2) weak heartbeat and
      high degree of rejection in groups receiving low doses of FK and RPM; (3) strong
      heartbeat and mild rejection in both high FK and RPM dose groups comparable to
      the results of the hearts treated with ciclosporin; (4) 1 animal in each high FK
      and RPM dose group showed possible signs of toxicity, and (5) the strength of the
      heartbeat was not a reliable indicator of the efficacy of an immunosuppressive
      drug. We conclude that even in a major histocompatibility mismatch model at the
      time of the strongest immune response (1 week), all three tested drugs can reduce
      the degree of rejection from severe (untreated allografts) to mild if given in an
      adequate dosage.

PMID- 1380459
TI  - Growth hormone treatment in children with preterminal chronic renal failure: no
      adverse effect on glomerular filtration rate.
AB  - Impaired growth and stunting remains a major therapeutic problem in children with
      chronic renal failure (CRF). Recombinant human growth hormone (rhGH) treatment
      may be beneficial, but concern has been raised about possible side-effects, i.e.
      deterioration of renal function and glucose intolerance. We have treated 10
      prepubertal children with CRF (median age 7.5 [1.7-10.0] years) with 4 IU rhGH/m2
      per day s.c. over a period of 1 year. Height velocity increased significantly (P
      less than 0.03) from basal 4.6 (2.0-14.0) cm/year to 9.7 (6.8-17.6) cm/year.
      Height velocity SDS for chronological age and for bone age increased in all
      children from basal median -2.3 to +3.8 (P less than 0.005). Median glomerular
      filtration rate (GFR) measured by single injection inulin clearance at onset was
      18 (11-66) ml/min per 1.73 m2 and did not change significantly during the
      treatment year. The loss of GFR as estimated by creatinine clearance was similar
      during the treatment year (median loss 1.3 ml/min per 1.73 m2) compared to the
      year before treatment (median loss 3.7 ml/min per 1.73 m2). Serum glucose levels
      during an oral glucose tolerance test did not change, but fasting as well as
      stimulated insulin levels increased significantly with time during the study
      period. It is concluded that the rhGH regimen employed was remarkably effective
      in improving growth velocity in children with CRF without adversely affecting
      GFR. Glucose homeostasis remained stable, but at the expense of increased serum
      insulin levels.

PMID- 1380461
TI  - Drug-protein binding kinetics in patients with type I diabetes.
AB  - Sera from 17 patients with Type I diabetes and 19 healthy volunteers have been
      examined to evaluate whether the kinetics of the binding of drugs to Site II of
      serum albumin is altered in diabetes. Stopped-flow measurements showed that the
      association velocity and the affinity constants of the fluorescent marker
      dansylsarcosine were significantly lower in diabetes (160 s-1 and 2.0 x 10(5)
      l.mol-1) than in non-diabetics (196 s-1 and 4.0 x 10(5) l.mol-1). The
      dissociation velocity was not different [20.3 s-1 vs. 19.4 s-1]. Although
      patients with a reduced albumin concentration were excluded the diabetics had
      significantly lower concentrations than the healthy volunteers. There was a
      significant correlation between decreased glycosylation of albumin and increased
      association velocity. The dissociation velocity constants were correlated with
      the molar concentration ratio of free fatty acids/human serum albumin. Thus, the
      extent of glycosylation and the amount of fatty acids bound per mole albumin can
      both affect the kinetics of drug binding to Site II. The lower affinity in
      patients with Type I diabetes is due to the increased in the glycoalbumin
      concentration.

PMID- 1380462
TI  - Interleukin (IL1 to IL7) gene expression in fetal liver and bone marrow stromal
      clones: cytokine-mediated positive and negative regulation.
AB  - Mouse bone marrow and fetal liver stromal clones have been analyzed for their
      cytokine mRNA expression. The reverse transcriptase polymerase chain reaction (RT
      PCR) has allowed us to detect interleukin (IL) mRNA levels, even if synthesized
      at levels not detectable by Northern blot analysis. We found that stromal cells
      possess the potential to constitutively express a much larger number of
      interleukins than previously described. The three stromal clones analyzed here
      expressed mRNA for IL3 and IL2, in addition to mRNA for IL1, IL4, IL6, and IL7.
      None of the stromal clones synthesized IL5 mRNA. Cytokine mRNA synthesis by
      stromal cells was found to be subjected to negative and positive regulation by
      interleukins. IL2, IL3, IL6, and IL7 gene expression was much more sensitive to
      cytokine regulation than that of IL1 and IL4.

PMID- 1380463
TI  - Tumor necrosis factor alpha in human long-term bone marrow cultures: distinct
      effects on nonadherent and adherent progenitors.
AB  - Although tumor necrosis factor alpha (TNF alpha) exerts a variety of activities
      on hematopoietic cells, suggesting it may have some potential therapeutic
      applications, its long-term effects on hematopoiesis are not well defined.
      Therefore, we took the advantage of long-term bone marrow cultures (LTBMCs) to
      evaluate the long-term role of TNF alpha on both the microenvironment and the
      hematopoietic progenitors. LTBMCs were inoculated with 100 U/ml of recombinant
      human TNF alpha (rhTNF alpha) either at the onset of the cultures (d0) or at day
      21 (d21) when the adherent layer (AL) was already established. Then TNF alpha was
      added at each weekly medium change. The cellularity and the content of
      progenitors in both the nonadherent layer (NAL) and AL, the formation of the AL,
      and the presence of various cytokines in the supernatants were examined weekly.
      The data showed 1) a strong and durable inhibitory effect on total nonadherent
      cells; 2) a rapid and transient inhibition of NA progenitors, whereas adherent
      progenitors were lately affected; and 3) microenvironmental changes consisting of
      the disappearance of adipocytes and the secretion of high levels of interleukin
      6. The results suggest that the inhibitory effects of TNF alpha on the NAL are in
      part counterbalanced by stromal modifications that in turn lead to a faster
      exhaustion of hematopoiesis.

PMID- 1380464
TI  - Aortic features in Tangier disease and pathogenetic considerations--Part I. Fatty
      dots and streaks.
AB  - Morphological studies of aortic fatty dots and streaks, and the adjacent normally
      appearing intima, in a 5 3/4-year-old boy who died of pneumonia, showed several
      hitherto unreported features. In lesions, lipid vacuoles and/or other cytoplasmic
      "inclusions" (ultrastructurally considered to present complex forms of lipids)
      were present on occasion in the endothelium but consistently involved the
      (intimal) smooth muscle cells (SMC). Similar changes were present in the adjacent
      intima, but were here less prominent and "tapered off" distally. A moderate
      number of macrophages also contained cytoplasmic lipids but such cells entirely
      free of lipid inclusions were observed, too. Most surprisingly, dilated and many
      cisternae of rough-surfaced endoplasmic reticulum (ER) in the SMC of lesions were
      associated spatially with cytoplasmic droplets and other forms of lipids. The
      results of these studies question the generally accepted central role of
      macrophages as being primarily involved in the pathogenesis of tissue changes in
      Tangier disease. It is possible that in view of the absence or paucity of high
      density lipoproteins (HDL) and alterations of (their) apo A-I and apo A-II (as
      well as of other lipids), the arterial SMC may be in some way involved in the
      metabolism of the above substances in this disorder. Support of this tentative
      (and highly speculative) assumption must await further work utilizing tissues and
      cells other than those containing macrophages and other derivatives of reticulo
      endothelial system.

PMID- 1380465
TI  - Binding of RNA by the alfalfa mosaic virus movement protein is biphasic.
AB  - The movement protein of alfalfa mosaic virus was expressed in Escherichia coli
      and purified by cation exchange chromatography. The purified protein bound single
      stranded RNA cooperatively in a biphasic manner. At protein saturation,
      RNA/protein complexes (designated 'primary complexes') were detected by a
      nitrocellulose-retention assay within 1 min of mixing, both at 4 and 22 degrees
      C. In contrast, an incubation of 30 min at 22 degrees C was necessary to obtain
      electrophoretically retarded complexes ('stabilized complexes'), containing a
      large number of protein molecules bound stably to each molecule of RNA.
      Stabilization did not take place at 4 degrees C. The rate of formation of the
      primary complexes was strongly dependent on protein concentration, and thus
      appeared limited by a bimolecular interaction. In contrast, the rate of
      stabilization was independent of protein concentration, suggesting that this
      process consisted of a rearrangement of the primary complexes without binding of
      additional protein molecules. In agreement with this suggestion, the amount of
      complexed RNA at equilibrium was the same when assayed by nitrocellulose
      retention and by electrophoretic retardation. The possibility that these peculiar
      kinetics could be caused by the presence of Tween 20 in the incubation media is
      discussed.

PMID- 1380466
TI  - Interleukin-1 beta induces the expression of an isoform of nitric oxide synthase
      in insulin-producing cells, which is similar to that observed in activated
      macrophages.
AB  - The suppressive and cytotoxic effects of interleukin-1 beta (IL-1 beta) on rodent
      insulin-producing cells observed in vitro are probably mediated through formation
      of nitric oxide (NO). In this study we demonstrate that IL-1-induced NO formation
      in isolated rat islets and insulin-producing HIT cells is more sensitive to
      inhibition by NG-monomethyl-L-arginine than to inhibition by NG-nitro-L-arginine,
      thus suggesting that IL-1-exposed insulin-producing cells express an isoform of
      nitric oxide synthase similar to that present in activated macrophages.
      Furthermore, IL-1 beta markedly increased the mRNA levels of the inducible
      macrophage form of nitric oxide synthase in HIT cells.

PMID- 1380467
TI  - Mutations in a putative agonist binding region of the AMPA-selective glutamate
      receptor channel.
AB  - The region preceding putative transmembrane segment M1 of the glutamate receptor
      (GluR) channel is well conserved among subunits and has been proposed to
      constitute a part of the agonist binding site. The functional significance of
      this region was examined by introducing point mutations into charged residues of
      the alpha 1 subunit of the mouse alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA)-selective GluR channel. The dose-response relationships of
      the mutant receptors were studied after expression in Xenopus oocytes by
      injection of the mutant alpha 1 subunit-specific mRNA together with the wild-type
      alpha 2-subunit-specific mRNA. Variable changes in the EC50 values for different
      agonists were found for the replacement of glutamic acid 398 by lysine and for
      the replacement of lysine 445 by glutamic acid. These residues may be involved in
      selective interaction of the GluR channel with agonists.

PMID- 1380468
TI  - Spontaneous thioester bond formation in alpha 2-macroglobulin, C3 and C4.
AB  - Purified alpha 2-macroglobulin and complement proteins C3 and C4 were treated
      with ammonia to break their intramolecular thioester bonds and reform the
      original free cysteinyl and glutamyl side chains. When this reaction was
      performed at low temperature a conformational intermediate was trapped which
      lacked a thioester, but which could refold to the native structure and
      spontaneously reform the thioester and full biological function. The findings
      suggest that these proteins may undergo spontaneous post-translational self
      modification forming the thioesters without involvement of enzymes or high energy
      metabolites such as ATP.

PMID- 1380469
TI  - Construction of dystrophin fusion proteins to raise targeted antibodies to
      different epitopes.
AB  - For the study of the structure and function relationship of dystrophin, defective
      in DMD, and for diagnostic purposes it is important to dispose of antibodies
      against different parts of the protein. We have made five different constructs
      for the expression of fusion proteins containing parts of the four domains of
      dystrophin. Two different recombinant expression vectors, pATH2 and pEX1, were
      used. Rabbits were immunized with the fusion products and several polyclonal
      antibodies were raised. At a later stage, monoclonal antibodies were also raised
      to some of the fusion proteins. One polyclonal antibody, named P20 AB, is
      directed against the region covering amino acid sequence 1749-2248 or the
      nucleotide sequence 5456-6953 of the mRNA, which corresponds to the major
      deletion-prone region of the DMD gene. We show the particular value, sensitivity
      and specificity of the P20 AB in dystrophin analysis.

PMID- 1380470
TI  - Conformation of two non-immunosuppressive FK506 analogs when bound to FKBP by
      isotope-filtered NMR.
AB  - The 3D structure of two unlabeled FK506 analogs, (R)- and (S)-[18-OH]ascomycin,
      when bound to [U-13C,15N]FKBP were determined by isotope-filtered 2D NMR
      experiments. The structures for the R and S isomers that bind tightly to FKBP but
      lack immunosuppressive activity are compared to each other and to the
      conformation of the potent immunosuppressant, ascomycin, when bound to FKBP. The
      results are interpreted in terms of calcineurin binding to the FKBP/ascomycin
      complex.

PMID- 1380471
TI  - Activation mechanism of human Hageman factor-plasma kallikrein-kinin system by
      Vibrio vulnificus metalloprotease.
AB  - Vivrio vulnificus, an opportunistic human pathogen, secretes a metalloprotease
      (VVP). The VVP inoculated into a guinea pig is known to generate bradykinin
      through activation of the Hageman factor-plasma kallikrein-kinin system. VVP was
      shown to possess the ability to activate the human system through the same
      mechanism as that clarified in the guinea pig system, namely, VVP converted both
      human zymogens (Hageman factor and plasma prekallikrein) to active enzymes
      (activated Hageman factor and plasma kallikrein), and the then generated
      kallikrein liberated bradykinin from high-molecular-weight kininogen. However, in
      the presence of plasma alpha 2-macroglobulin (alpha 2M), the VVP action was
      drastically decreased. This finding suggests that the human system might be
      activated only at the interstitial-tissue space which contains negligible amounts
      of alpha 2M or in the bloodstream of the individuals whose plasma alpha 2M level
      is extremely reduced.

PMID- 1380472
TI  - The molecular mechanism of the control of excitation energy dissipation in
      chloroplast membranes. Inhibition of delta pH-dependent quenching of chlorophyll
      fluorescence by dicyclohexylcarbodiimide.
AB  - Non-radiative dissipation of absorbed excitation energy in chloroplast membranes
      is induced in the presence of the trans-thylakoid proton motive force; this
      dissipation is measured as high energy state quenching of chlorophyll
      fluorescence, qE. It has been suggested that this results from a low pH-induced
      structural alteration in the light harvesting complex of photosystem II, LHCII
      [(1991) FEBS Letters 292, 1-4]. The effect of the carboxyl-modifying agent,
      dicyclohexylcarbodiimide (DCCD), on energy dissipation in chloroplast membranes
      has been investigated. At concentrations below that required to inhibit electron
      transport, DCCD caused a decrease in the steady state delta pH, completely
      inhibited qE and also inhibited the low pH-dependent induction of qE. DCCD
      binding to polypeptides in the 22-28 kDa range correlated with inhibition of qE.
      It is suggested that DCCD reacts with amino acid residues in LHCII whose
      protonation is the primary event in the induction of energy dissipation. This
      LHCII domain may be identical to one forming a proton channel linking the site of
      PSII-dependent water oxidation to the thylakoid lumen [(1990) Eur. J. Biochem.
      193, 731-736].

PMID- 1380473
TI  - Office aeroallergen sampling.
AB  - Aeroallergen sampling is a simple procedure that can be performed in any
      physician's office. The necessary equipment is a pollen and mold collecting
      device, a microscope with an eye-piece micrometer, pollen stain, and appropriate
      slides. The inexperienced observer can learn to count easily recognizable pollen
      and mold, such as ragweed and Alternaria in a matter of minutes. The counting can
      be simple (of one or two pollens) and can be complex, including counting of
      various molds under oil immersion.

PMID- 1380474
TI  - [Brachytherapy: endobronchial irradiation for primary and secondary bronchial
      tumors].
AB  - Intrabronchial obstruction is one of the serious complications of primary and
      secondary lung tumors. Brachytherapy (intraluminal irradiation) aims at
      palliation and opening airway obstruction. Of our first 10 patients, 4 had
      primary and 6 metastatic pulmonary lesions. Brachytherapy was administered
      through the fiberoptic bronchoscope under topical anesthesia from a 192iridium
      source delivered with an afterload system. In 3 patients laser therapy was used
      initially. In 6 complete opening of the airway was achieved, and in 3 others
      partial opening. In all patients there was symptomatic relief without significant
      side-effects. We conclude that endobronchial brachytherapy is a safe, useful
      procedure for palliation of malignant endobronchial obstruction.

PMID- 1380475
TI  - Can somatostatin prevent injection pancreatitis after ERCP?
AB  - In a double-blind randomized study, 30 patients received somatostatin infusion
      during ERCP and 30 patients placebo with the aim of evaluating whether
      somatostatin can reduce the incidence of injection pancreatitis. S-amylase, U
      amylase and S-lipase were evaluated before, during and after (up to 48 hours)
      ERCP. C-peptide was also determined as a marker of the function of the endocrine
      pancreas. While no statistically significant effect of somatostatin in terms of
      amylase and lipase was to be found, somatostatin did significantly decrease c
      peptide levels in plasma, indicating that the peptide inhibited beta-cell
      secretion. About 40% of patients in the somatostatin group and about 50% in the
      placebo group showed signs of injection pancreatitis (elevated levels of enzymes)
      and in both groups there are patients with clinically apparent pancreatitis.

PMID- 1380476
TI  - Alpha-fetoprotein-producing pancreatic cancer--a case report and review of 28
      cases.
AB  - The case of a female patient with an alpha-fetoprotein (AFP)-producing acinar
      cell carcinoma of the pancreas is reported, and 28 cases in the literature are
      reviewed. In our case, the serum AFP level declined drastically after removal of
      the tumor, but increased when widespread metastases appeared. AFP was detected in
      the cytoplasm of the cancer cells by immunohistochemical staining. Immunoelectron
      microscopic studies revealed AFP on the endoplasmic reticulum of the cancer
      cells. Of the 28 cases with AFP-producing pancreatic cancer, liver metastases
      were identified in 21 cases (76% overall). There was no correlation between the
      serum AFP level and liver metastases. Immunohistochemical studies revealed
      localization of AFP at the primary lesion in 6 out of eight cases tested. In
      cases of AFP-producing pancreatic cancer, serum AFP levels are useful for the
      diagnosis and as a marker for evaluating recurrent disease and therapeutic
      response, and for the management of gastrointestinal disease it should be
      remembered that some pancreatic cancers produce AFP.

PMID- 1380477
TI  - The degree of variability in the amino terminal region of the E2/NS1 protein of
      hepatitis C virus correlates with responsiveness to interferon therapy in viremic
      patients.
AB  - We investigated amino acid heterogeneity in the variable regions of the E2/NS1
      viral protein in interferon-responsive and interferon-nonresponsive patients with
      chronic hepatitis C virus infection. The study assessed whether any particular
      heterogeneity pattern(s) could be useful in predicting responsiveness to
      interferon treatment. The nucleic acid sequences of the hepatitis C virus genome
      were analyzed from six patients with chronic hepatitis treated with an interferon
      beta, three of whom did not respond to the therapy and another three who showed
      remarkable improvement in the serum levels of liver enzymes and hepatitis C virus
      RNA after 6 mo. The complementary DNA clones propagated from each of the
      nonresponders showed significant diversity of both nucleotide and amino acid
      sequence, especially at the hypervariable region 1 within the putative E2/NS1
      gene of the virus, suggesting that these patients were infected with a large
      heterogeneous pool of hepatitis C virus variants. In contrast, the responders
      showed little or no diversity in the sequence of the complementary DNA clones,
      suggesting that they were infected with one or a small population of viral
      genotypes containing significantly less variability in the E2/NS1 hypervariable
      region 1. These results suggested that a large variable population of hepatitis C
      virus genotypes is implicated in patients who are nonresponders to interferon
      treatment. In addition, a significant change in the hepatitis C virus genotype
      population was observed in nonresponders after interferon treatment. This may
      reflect a differential viral sensitivity to interferon, selective immune pressure
      by the host or both.

PMID- 1380478
TI  - Spontaneous exacerbation of disease activity in patients with chronic delta
      hepatitis infection: the role of hepatitis B, C or D?
AB  - Forty-six patients with chronic hepatitis delta virus infection were followed
      between 6 and 116 mo (mean = 32.8 mo; median = 24 mo). Nineteen patients (41%)
      demonstrated clinical courses with episodes of biochemical reactivation (ALT
      levels greater than or equal to 10 times baseline values [group A]). Twenty-seven
      patients (59%) had stable clinical courses without biochemical reactivation
      (group B). Patients in group A were younger than those in group B (30.5 vs. 35.3
      yr; p = 0.03), were less likely to be intravenous drug abusers (16% vs. 52%; p =
      0.01) and were more likely to be homosexual (58% vs. 22%; p = 0.01). Serum
      hepatitis B virus DNA, hepatitis delta virus RNA, IgM antibody to HBc, HBeAg,
      antibody to HBe and IgG and IgM antibody to hepatitis delta virus were measured
      in all patients. In group A, these markers were studied before and during
      reactivation and during remission. In group B, these parameters were studied in a
      random fashion at 7- to 10-mo intervals. The presence of antibodies to human
      immunodeficiency virus and hepatitis C virus was assessed in all patients. A
      total of 38 biochemical reactivation episodes was noted among the 19 patients in
      group A. Eleven had sequential changes in hepatitis delta virus markers,
      suggesting that the exacerbations were due to hepatitis delta virus. In three,
      the sequential changes of viral markers were consistent with the exacerbations
      due to hepatitis B virus. In five other patients, no sequential changes in viral
      markers could be demonstrated to correlate with the biochemical
      exacerbations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380479
TI  - Liver/kidney microsome antibody type 1 and hepatitis C virus infection.
AB  - Recent studies have shown that hepatitis C virus antibodies are present in a
      large proportion of patients with autoimmune hepatitis type 2. We have studied 83
      patients with liver/kidney microsome antibody-positive type 1 hepatitis.
      Hepatitis C virus antibodies were sought in every case by second-generation tests
      (hepatitis C virus enzyme-linked immunosorbent assay and recombinant immunoblot
      assay). Hepatitis C virus RNA sequences were sought in 22 patients (12 with
      recombinant immunoblot assay-positive results and 10 with recombinant immunoblot
      assay-negative results) by means of polymerase chain reaction and by use of
      primers located in the 5' noncoding region. Sixty-four patients (77%) had
      positive results for hepatitis C virus antibodies in the enzyme-linked
      immunosorbent assay test, and 41 (49.3%) were confirmed by recombinant immunoblot
      assay. Hepatitis C virus RNA sequences were found in all the recombinant
      immunoblot assay-positive patients but in none of the 10 who were recombinant
      immunoblot assay-negative. The recombinant immunoblot assay-negative patients
      were younger than those who were positive (13 +/- 11 vs. 50 +/- 11 years) and had
      higher gamma-globulin levels and liver/kidney microsome antibody-positive type 1
      titers (61% had a titer of 1:1,000 or more, vs. only 17% of the recombinant
      immunoblot assay-positive patients).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380480
TI  - Hepatitis B and C viral infections in patients with hepatocellular carcinoma.
AB  - The prevalence of hepatitis B and C virus infections was studied in 70 patients
      diagnosed as having hepatocellular carcinoma. In addition to viral serological
      markers, serum hepatitis B virus DNA and hepatitis C virus RNA were determined
      with a nested polymerase chain reaction assay. Twelve patients (17%) were HBsAg
      positive, 26 (37%) had antibodies to HBs, HBc or both and 32 (46%) were negative
      for all hepatitis B virus serological markers. Prevalence of the antibody to
      hepatitis C virus was 63% (44 patients). Hepatitis B virus DNA was detected in 24
      of the 66 tested patients (36%). Twelve of these hepatitis B virus DNA-positive
      patients were HBsAg negative (seven were positive for antibody to HBs, antibody
      to HBc or both and five were negative for all hepatitis B virus serological
      markers). Hepatitis C virus RNA was found in 42 of 68 patients (62%). A high
      correlation (95%) existed between hepatitis C virus RNA and hepatitis C virus
      antibodies. Nevertheless, two patients without antibody to hepatitis C virus had
      serum hepatitis C virus RNA sequences. Coinfection by the two viruses was
      detected in nine subjects (14%), but no clinical differences were found between
      these and the rest of the patients. We conclude that nearly 90% (62 of the 70
      patients studied) of cases of hepatocellular carcinoma in our geographical area
      are related to hepatitis virus infections (detected by serological or molecular
      studies). Hepatitis C is more prevalent than hepatitis B virus in patients with
      hepatocellular carcinoma, and the infection is still active when the tumor is
      diagnosed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380481
TI  - Cytokeratin expression in mucinous sweat gland carcinomas: an immunohistochemical
      analysis of four cases.
AB  - Four mucinous sweat gland carcinomas were examined for the distribution of
      cytokeratin (CK) polypeptides using immunohistochemical techniques on paraffin
      embedded sections. All the tumour specimens reacted with monoclonal antibodies to
      CK 7, CK 8, CK 18 and CK 19. Antibodies to CK 1, CK 1/2/10/14, CK 1/5/10/11, CK
      13, CK 14 and CK 20 did not stain any of the carcinomas. The results add
      additional support to the notion that mucinous sweat gland carcinoma represents a
      tumour histogenetically related to the eccrine secretory coil. Furthermore, the
      absence of CK 20 might significantly contribute to the differentiation of this
      tumour from cutaneous metastases from gastrointestinal carcinomas.

PMID- 1380482
TI  - Analyzing and comparing nucleic acid sequences by hybridization to arrays of
      oligonucleotides: evaluation using experimental models.
AB  - An efficient method was developed for making complete sets of oligonucleotides of
      defined length, covalently attached to the surface of a glass plate, by
      synthesizing them in situ. A device carrying all octapurine sequences was used to
      explore factors affecting molecular hybridization of the tethered
      oligonucleotides, to develop computer-aided methods for analyzing the data, and
      to test the feasibility of using the method for sequence analysis. Further
      development is needed before the method can be used routinely, but our work shows
      that it has a number of potential advantages over gel-based methods: it should be
      easy to automate; the quality of the sequence results can be evaluated
      statistically; it provides a powerful way of comparing related sequences and
      detecting mutation; it can be applied to both DNA and RNA; and specific motifs
      can be incorporated into all sequences of the array to focus analysis on
      sequences of biological interest.

PMID- 1380483
TI  - Mapping the human acetylcholinesterase gene to chromosome 7q22 by fluorescent in
      situ hybridization coupled with selective PCR amplification from a somatic hybrid
      cell panel and chromosome-sorted DNA libraries.
AB  - To establish the chromosomal location of the human ACHE gene encoding the
      acetylcholine hydrolyzing enzyme acetylcholinesterase (ACHE, acetylcholine
      acetylhydrolase, E.C. 3.1.1.7), a human-specific polymerase chain reaction (PCR)
      procedure that supports the selective amplification of ACHE DNA fragments from
      human genomic DNA was employed with 19 human-hamster somatic cell hybrids
      carrying one or more human chromosomes. Informative ACHE-specific PCR fragments
      were produced from two cell lines, both of which include human chromosome 7, but
      not with DNA from 17 cell hybrids carrying various combinations of all human
      chromosomes other than 7. Fluorescent in situ hybridization of biotinylated ACHE
      DNA with metaphase chromosomes from human peripheral blood lymphocytes revealed
      prominent labeling on the 7q22 position. Therefore, further tests were performed
      to confirm the chromosome 7 location. DNA samples from the two cell lines
      including chromosome 7 and the ACHE gene were positive with PCR primers
      informative for the human cystic fibrosis CFTR gene, known to reside at the
      7q31.1 position, but negative for the ACHE-related butyrylcholinesterase (BCHE,
      acylcholine acylhydrolase, E.C. 3.1.1.8) gene, mapped at the 3q26-ter position,
      confirming that these lines contain chromosome 7 but not chromosome 3. In
      contrast, three other cell lines including chromosome 3, but not 7, were BCHE
      positive and ACHE-negative. In addition, genomic DNA from a sorted chromosome 7
      library supported the production of ACHE- but not BCHE-specific PCR products,
      whereas with DNA from a sorted chromosome 3 library, the BCHE but not the ACHE
      fragment was amplified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380484
TI  - 11p15.5-specific libraries for identification of potential gene sequences
      involved in Beckwith-Wiedemann syndrome and tumorigenesis.
AB  - Constitutional and somatic chromosomal abnormalities of the chromosome 11p15
      region are involved in an overgrowth malformation syndrome, the Beckwith
      Wiedemann syndrome (BWS), and in several types of associated tumors. The bias in
      parental origin for the different etiologic forms of this syndrome and for loss
      of heterozygosity in the tumors suggests that a gene (or genes) mapping to this
      region undergoes genomic imprinting. However, the precise localization of the
      locus (or loci) for the BWS and associated tumors is still unknown and more
      markers are required. We therefore isolated 11p15 markers from two libraries: the
      first one obtained by microdissection of the chromosome 11p15.5 region and the
      second one, a phage library, constructed from a hybrid cell line containing this
      region as its sole human DNA. Of 19 microclones isolated from the microdissection
      library, 11 were evolutionarily conserved. Four phage clones were isolated; one
      (D11S774) detected a highly informative variable number of tandem repeats (VNTR)
      and another (D11S773) a biallelic polymorphism. These clones were sublocalized
      using a panel of somatic cell hybrids that defines eight physical intervals in
      11p15.5. Twenty-one clones map to the distal interval that harbors the BWS locus.

PMID- 1380485
TI  - PCR amplification and analysis of yeast artificial chromosomes.
AB  - A strategy for the analysis of yeast artificial chromosome (YAC) clones that
      relies on polymerase chain reaction (PCR) amplification of small restriction
      fragments from isolated YACs following adapter ligation was developed. Using this
      method, termed YACadapt, we have amplified several YACs from a human Xq24-qter
      library and have used the PCR products for physical mapping by somatic cell
      hybrid deletion analysis and fluorescent in situ hybridization. One YAC, RS46,
      was mapped to band Xq27.3, near the fragile X mutation. The PCR product is an
      excellent renewable source of YAC DNA for analyses involving hybridization of YAC
      inserts to a variety of DNA/RNA sources.

PMID- 1380486
TI  - Multiplex PCR amplification of three microsatellites within the CFTR gene.
AB  - Multiplex PCR amplification has been developed for three highly polymorphic
      microsatellites (IVS8CA, IVS17BTA, and IVS17BCA) located in intronic regions of
      the CFTR (cystic fibrosis (CF) transmembrane conductance regulator) gene. The
      triplex PCR reaction required different concentrations of each pair of primers
      and labeling of primers in the same reaction. Total informativity is obtained in
      90.25% of couples requiring analysis of polymorphisms, and when triplex
      microsatellite analysis is combined with analysis for the six most common CF
      mutations in the Spanish population, informativity reaches more than 99%.

PMID- 1380487
TI  - Thermal model for the local microwave hyperthermia treatment of benign prostatic
      hyperplasia.
AB  - A system for the noninvasive localized, hyperthermia treatment of benign
      prostatic hyperplasia was investigated. The system uses a microwave transrectal
      antenna with a water cooled jacket to achieve localized hyperthermia. The purpose
      of this study is to model the temperature rise in the prostate and in the
      surrounding tissue during treatment. The SAR distribution for the transrectal
      probe is measured in a muscle tissue equivalent phantom. The SAR information is
      used with a finite element solution of the bioheat transfer equation to give the
      temperature rise during the treatment. Also the finite element solution is
      further used to determine the effect of the microwave power, the cooling fluid
      temperature and the blood perfusion on the tissue temperature rise. The results
      of the solution are compared to temperature measurements in a canine protocol. It
      was found that the maximum temperature rise in the tissue during treatment is 44
      degrees C at a depth of 2 cm from the rectal mucosa.

PMID- 1380488
TI  - IL-6 and NF-IL6 in acute-phase response and viral infection.
AB  - NF-IL6 was originally identified as a DNA-binding protein responsible for IL-1
      stimulated IL-6 induction. Direct cloning of NF-IL6 revealed its homology with
      C/EBP. C/EBP is expressed in liver and adipose tissues and is supposed to
      regulate several hepatocyte- and adipocyte-specific genes. In contrast, NF-IL6 is
      suppressed in normal tissues, but is rapidly and drastically induced by LPS or
      inflammatory cytokines such as IL-1, TNF, and IL-6. NF-IL6 can also bind to the
      regulatory region of various genes including IL-8, G-CSF, IL-1 and immunoglobulin
      genes. Furthermore, NF-IL6 is shown to be identical to IL-6DBP, a DNA-binding
      protein responsible for IL-6-mediated induction in acute-phase proteins,
      demonstrating that NF-IL6 is responsible for the genes regulated by IL-6. These
      results indicate that NF-IL6 may be a pleiotropic mediator of many inducible
      genes involved in acute, immune, and inflammatory responses, like NFkB. In this
      regard, it is noteworthy that both an NF-IL6 binding site and an NFkB binding
      site are present in the inducible genes such as IL-6, IL-8, and several acute
      phase genes. On the other hand, accumulating evidence has revealed that
      overproduction of IL-6 may be responsible for the pathogenesis and/or several
      symptoms of a variety of diseases, including autoimmune diseases, malignancies,
      and viral diseases. At present, the molecular mechanisms of abnormal expression
      of the IL-6 gene are not known. Recently it has become evident that interplays
      between viral proteins and cellular proteins play an important role in viral
      oncogenesis and infection. The fact that NF-IL6 binds to the enhancer core
      sequences of various viruses strongly suggests a possible relationship of virus
      infection and IL-6 expression. In fact some evidence (Mahe et al. 1991, Spergel
      et al. 1992) indicates that NF-IL6 may interact with viral gene enhancers or
      viral products, although there are no definite data about the involvement of NF
      IL6 in viral pathogenesis. Future studies will be required to clarify whether or
      not the interplay between NF-IL6 and viral infection is responsible for
      deregulation of the IL-6 gene.

PMID- 1380489
TI  - Indigenous silicone rubber endoprosthesis for malignant esophago-pulmonary
      fistula.
AB  - Endoscopic placement of an esophageal endoprosthesis is the most rational therapy
      for relieving the distress of malignant esophago-pulmonary fistula. The
      commercial prostheses are very expensive for widespread use in India. We have
      indigenously prepared silicone rubber endoprostheses. The wall of the prosthesis
      was hardened in a graded manner until the desired resistance to compression with
      flexibility is achieved. This prosthesis was placed successfully in five patients
      with malignant esophago-pulmonary fistula. Dysphagia and aspiration were relieved
      in all the patients. One patient had delayed esophageal perforation and died of
      massive bleeding 3 weeks after the placement of prosthesis. The indigenous
      endoprosthesis is cost-effective and safe.

PMID- 1380490
TI  - Hepatitis C virus in patients with acute and chronic liver disease.

PMID- 1380491
TI  - Immunoblot analysis of antibody responses to Shigella dysenteriae type 1
      infection.
AB  - Immunoblot analysis was used to identify the antigenic components of the outer
      membrane protein (OMP) extract from Sh. dysenteriae type 1 that may be relevant
      in protection against infection. The OMPs were extracted by ultrasonic disruption
      followed by Sarkosyl extraction. The macromolecular bands were separated by
      sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE),
      electroeluted to a nitrocellulose matrix and complexed with peroxidase conjugated
      antibodies in human convalescent sera. IgG specific reaction was found to a major
      antigenic component at 57 kilodaltons. In addition, weakly reactive three
      antigenic determinants of greater than 57 kD and four of less than 57 kD were
      found. Control sera from a rabbit immunized against OMP also exhibited a similar
      pattern of antigenic reactivity. Some of the OMPs with high antigenicity may be
      important in immunoprophylaxis.

PMID- 1380493
TI  - The nuclear envelope of the yeast Saccharomyces cerevisiae.

PMID- 1380492
TI  - Methyl parathion induced regional alterations in the regulatory proteins during
      critical stage of central nervous system development in albino rat pups.
AB  - Sublethal doses of methyl parathion (O,O-dimethyl-O-nitrophenyl- thiophosphate)
      injected intraperitoneally to 15 and 21 day old rat pups induced regional
      alterations in the central nervous system (CNS) in the levels of total RNA, total
      proteins, modulatory protein Calmodulin (CaM), in the activity levels of membrane
      bound enzyme Ca(2+)-ATPase and phospholipids. Levels of RNA and total proteins
      increased considerably in 15 days old methyl parathion treated (MPT) rat pups.
      Contrary to this the RNA and total protein content exhibited remarkable decrease
      in 21 day old methyl parathion treated animals. Calmodulin level showed an
      increase in cerebral cortex and brain stem and decrease in cerebellum and spinal
      cord in 15 day old methyl parathion treated rat pups. Whereas the level of
      Calmodulin decreased in cerebral cortex and cerebellum and increased in brain
      stem and spinal cord in 21 day old methyl parathion treated rat pups. Activity
      levels of calcium dependent ATPase showed significant inhibition in all the
      regions of Central Nervous System (CNS) of 15 and 21 day old methyl parathion
      treated rat pups. Phospholipids showed a general increase in all the regions of
      Central Nervous System on methyl parathion exposure. In the light of these
      observations, it has been suggested that the molecular regulatory mechanisms
      involving Ca2+/CaM are rendered inefficient due to toxic impact of methyl
      parathion.

PMID- 1380494
TI  - [Current status and trends in treatment of scleroderma].
AB  - Owing to the wide variety of symptoms, the long clinical course, the inadequate
      knowledge of the points at which therapeutic action is appropriate and the
      difficulty of obtaining objective measurements of the treatment results, therapy
      for systemic sclerosis has to be planned individually. Besides basic
      recommendations (avoidance of noxious substances, sensible diet, keeping warm,
      active exercises), physiotherapy and psychological guidance, the therapy is
      directed at three pathogenetic complexes. Among the vasoactive substances the
      prostacyclins, calcium channel blockers and angiotensin-converting-enzyme
      inhibitors (in the case of complicated renal involvement) are recommended. They
      inhibit the thrombocyte hyperaggregation and lead to vasodilatation. The anti
      inflammatory substances prednisolone and azathioprine also exert
      immunosuppressant (and cytotoxic) effect. Their use is indicated in inflammatory,
      immunologically active forms of systemic sclerosis. Antifibrotic agents inhibit
      cross-link formation, prolylhydroxylase, extrusion of collagen from fibroblasts
      and, thus, collagen synthesis. In addition, they favour the degradation of
      collagen via the activation of collagenase. Good results have been reported with
      penicillamine and penicillin G. Pentoxyphyllin leads to vasodilatation and also
      inhibits collagen metabolism. Promising agents and procedures for future use
      include cyclosporin A, CD4 antibodies, photopheresis, interferon gamma and factor
      XIII. A critical attitude to therapy and a great deal of patience are necessary
      to avoid harming the patients, especially as it is often some months before any
      effects of the treatment are seen.

PMID- 1380495
TI  - Immunocytochemical localisation of substance P-like nerves in the cardiac ganglia
      of the monkey (Macaca fascicularis).
AB  - Substance P-like immunoreactive (SP-IR) nerves formed 2 types of relationships
      with nerve cells in the cardiac ganglia of the monkey (Macaca fascicularis). The
      first type consisted of varicose SP-IR nerve fibres that ramified throughout the
      cardiac ganglia, forming a loose network with several nerve cell bodies. The
      second type consisted of several nerve cell bodies enwrapped by a dense
      pericellular (basket-like) investment of varicose SP-IR nerve fibres. Numerous SP
      IR nerve fibres formed perivascular networks around the walls of the blood
      vessels within the cardiac ganglia and the muscle. The cardiac muscle cells were
      also innervated either by an isolated single varicose SP-IR nerve fibre or by
      complex networks. At the ultrastructural level, the substance P reaction product
      appeared to be associated with the microtubules and the outer mitochondrial
      membranes of labelled axons. Substance P reaction product was also localised on
      the membranes of small agranular vesicles of the labelled axon terminals. The SP
      IR axons and axon terminals were closely related to the nerve cell bodies and
      they occurred either singly or in small groups. Most of the axons were enwrapped
      by a sheath from the adjacent Schwann cells which often exhibited pseudopodia
      like processes. None of the axon terminals was observed to make synaptic contact
      with the cell bodies. However, a few axoaxonal contacts involving SP-IR and non
      SP-IR axon terminals were present, the significance of which is not understood.
      Several axon terminals lay close to blood vessels, and may modulate the activity
      of these vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380496
TI  - O3-induced airway hyperresponsiveness to noncholinergic system and other stimuli.
AB  - The effect of O3 exposure (3 ppm, 1 h) on the in vivo and in vitro airway
      responsiveness, as well as the changes in cell contents in bronchoalveolar lavage
      (BAL) fluid, were evaluated 16-18 h after O3 exposure in sensitized and
      nonsensitized male guinea pigs. The sensitization procedure was performed through
      repeated inhalation of ovalbumin for 3 wk. Increase in pulmonary insufflation
      pressure produced by the excitatory nonadrenergic noncholinergic (eNANC) system,
      histamine, and antigen were assessed in in vivo conditions, whereas airway
      responsiveness to histamine and substance P was evaluated in in vitro conditions
      by use of tracheal chains with or without epithelium and lung parenchymal strips.
      We found that O3 exposure 1) increased the neutrophil content in BAL fluids in
      both sensitized and nonsensitized guinea pigs, 2) caused hyperresponsiveness to
      eNANC stimulation in nonsensitized guinea pigs (although combination of
      sensitization and O3 exposure paradoxically abolished the hyperresponsiveness to
      eNANC stimulation), 3) increased the in vivo bronchoconstrictor responses to
      histamine and antigen, 4) caused hyperresponsiveness to substance P in
      nonsensitized tracheae with or without epithelium and in sensitized tracheae with
      epithelium, 5) did not modify the responsiveness to histamine in tracheae with or
      without epithelium (and in addition, epithelium removal caused
      hyperresponsiveness to histamine even in those tracheae exposed to O3), and 6)
      produced hyperresponsiveness to histamine in lung parenchymal strips either from
      sensitized or nonsensitized guinea pigs.

PMID- 1380497
TI  - Minireview series. Mitochondrial channels.

PMID- 1380498
TI  - The mitochondrial megachannel is the permeability transition pore.
AB  - Single-channel electrophysiological recordings from rat liver mitoplast membranes
      showed that the 1.3-nS mitochondrial megachannel was activated by Ca++ and
      inhibited by Mg++, Cyclosporin A, and ADP, probably acting at matrix-side sites.
      These agents are known to modulate the so-called mitochondrial permeability
      transition pore (Gunter, T. E., and Pfeiffer, D. R. (1990) Am. J. Physiol. 258,
      C755-C786) in the same manner. Furthermore, the megachannel is unselective, and
      the minimum pore size calculated from its conductance is in agreement with
      independent estimates of the minimum size of the permeabilization pore. The
      results support the tentative identification of the megachannel with the pore
      believed to be involved in the permeabilization process.

PMID- 1380499
TI  - Voltage activation of heart inner mitochondrial membrane channels.
AB  - The patch clamp records obtained from mitoplast membranes prepared in the
      presence of a calcium chelator generally lack channel activity. However,
      multiconductance channel (MCC) activity can be induced by membrane potentials
      above +/- 60 mV [Kinnally et al., Biochem. Biophys. Res. Commun. 176, 1183-1188
      (1991)]. Once activated, the MCC activity persists at all voltages. The present
      report characterizes the activation by voltage of multiconductance channels of
      rat heart inner mitochondrial membranes using patch-clamping. In some membrane
      patches, the size of single current transitions progressively increases with time
      upon application of voltage. The inhibitor cyclosporin has also been found to
      decrease channel conductance in steps. The results suggest that voltage-induced
      effects which are inhibited by cyclosporin A are likely to involve either an
      increase in effective pore diameter or the assembly of low-conductance units. In
      activated patches, we have found at high membrane potentials (e.g., 130 mV)
      changes in conductance as high as 5 nS occurring in large steps (up to 2.7 nS).
      These were generally preceded by a smaller transition. Similar results were
      obtained less frequently at lower voltages. These results can be explained on the
      assumption that once assembled the channels may act in unison.

PMID- 1380501
TI  - Determination of the number of polypeptide subunits in a functional VDAC channel
      from Saccharomyces cerevisiae.
AB  - Genes encoding VDAC proteins containing specific site-directed amino acid
      alterations were introduced into wild-type Saccharomyces cerevisiae. The mutant
      VDAC proteins form channels with ion selectivities very different from that of
      the wild-type channel. Therefore, the resulting yeast strains express two
      different genes capable of coding for functional, yet distinct, VDAC channels. If
      VDAC were an oligomeric channel, analysis of VDAC from these strains should have
      revealed not only the presence of channels with wild-type or mutant selectivity
      but also channels with intermediate selectivities. While channels with wild-type
      and mutant selectivities were observed with approximately equal frequency, no
      channels with intermediate selectivity were observed. Sufficient observations
      were performed with two different mutant genes K61E.K65E and K19E.K61E) that the
      likelihood of having missed hybrid channels was less than 1 in 10(7). These
      findings favor the hypothesis that each functional VDAC channel is composed of a
      single 30-kDa polypeptide chain.

PMID- 1380500
TI  - Transmembrane arrangement of mitochondrial porin or voltage-dependent anion
      channel (VDAC).
AB  - Porin or voltage-dependent anion-selective channel (VDAC) is the main protein
      responsible for the high permeability of the outer mitochondrial membrane. The
      mitochondrial porin is mainly composed of sided beta-strands, in analogy with
      bacterial porin, whose structure has been resolved at 1.8 A resolution. In
      mitochondrial porins the N-terminal region forms an amphipathic alpha-helix, a
      structure conserved in organisms very distant from the evolutionary point of
      view. This part of the protein is exposed to the water phase, as demonstrated by
      ELISA assays. Various extramembranous loops have been identified by specific
      proteolytic cleavages. These overall, combined results were used to draw a model
      of the transmembrane arrangement of mammalian porin. This model is compared to
      other mitochondrial and bacterial porin models.

PMID- 1380502
TI  - The emerging picture of mitochondrial membrane channels.

PMID- 1380503
TI  - The cation-selective substate of the mitochondrial outer membrane pore: single
      channel conductance and influence on intermembrane and peripheral kinases.
AB  - The polyanion-induced substate of the outer mitochondrial membrane was studied in
      vivo and in vitro. Study of the substate in artificial bilayers showed that it is
      highly cation selective. The induction of the substate in intact mitochondria
      leads to a complete inhibition of the intermembrane kinases, such as creatine
      kinase and adenylate kinase, which were excluded from the external ATP pool.
      Peripheral kinases, such as hexokinase, were blocked when they utilized internal
      ATP. The results with intact mitochondria suggested the existence of two regions
      of the outer membrane containing channels of different states, which may be
      involved in the regulation of intermembrane and peripheral kinases.

PMID- 1380504
TI  - A soluble mitochondrial protein increases the voltage dependence of the
      mitochondrial channel, VDAC.
AB  - A soluble protein isolated from mitochondria has been found to modulate the
      voltage-dependent properties of the mitochondrial outer membrane channel, VDAC.
      This protein, called the VDAC modulator, was first found in Neurospora crassa and
      then discovered in species from other eukaryotic kingdoms. The modulator
      containing fraction (at a crude protein concentration of 20 micrograms/ml)
      increases the voltage dependence of VDAC channels over 2-3-fold. At higher
      protein concentrations (50-100 micrograms/ml), some channels seem to remain in a
      closed state or be blocked while others display the higher voltage dependence and
      are able to close at low membrane potentials. By increasing the steepness of the
      voltage-dependent properties of VDAC channels, this modulator may serve as an
      amplifier in vivo to increase the sensitivity of the channels in response to
      changes in the cell's microenvironment, and consequently, regulate the metabolic
      flux across the outer mitochondrial membrane by controlling the gating of VDAC
      channels.

PMID- 1380505
TI  - Binding of a synthetic targeting peptide to a mitochondrial channel protein.
AB  - Membrane crystals of the mitochondrial outer membrane channel VDAC (porin) from
      Neurospora crassa were incubated with a 20-amino-acid synthetic peptide
      corresponding to the N-terminal targeting region of subunit IV of cytochrome
      oxidase. The peptide caused disordering and contraction of the crystal lattice of
      the membrane arrays. Also, new stain-excluding features were observed on the
      peptide-treated arrays which most likely correspond to sites at which the peptide
      accumulates. The stain exclusion zones associated with binding of the targeting
      peptide (and with binding of apocytochrome c in an earlier study) have been
      localized on a two-dimensional density map of frozen-hydrated, crystalline VDAC
      previously obtained by cryo-electron microscopy. The results indicate that both
      the peptide and cytochrome c bind to protein "arms" which extend laterally
      between the channel lumens. The finding that imported polypeptides bind to a
      specific region of the VDAC protein implicates this channel in the process by
      which precursor proteins are recognized at and translocated across the
      mitochondrial outer membrane.

PMID- 1380506
TI  - The mitochondrial benzodiazepine receptor: evidence for association with the
      voltage-dependent anion channel (VDAC).
AB  - Specific, high-affinity receptors for numerous drugs have recently been localized
      to mitochondrial membrane proteins. This review discusses the association of the
      mitochondrial receptor for benzodiazepines (mBzR) with the voltage-dependent
      anion channel (VDAC), indicating a possible auxiliary role for VDAC as a putative
      drug binding protein. The proposed subunit composition of the purified mBzR
      complex isolated from rat kidney mitochondria includes VDAC, which functions as a
      recognition site for benzodiazepines (e.g., flunitrazepam), the adenine
      nucleotide carrier (ADC), and an 18 kDa outer membrane protein identified by
      covalent labelling with the mBzR antagonists isoquinoline carboxamides (e.g.,
      PK14105).

PMID- 1380508
TI  - Evidence for extra-mitochondrial localization of the VDAC/porin channel in
      eucaryotic cells.
AB  - The expression of bacterial porin in outer membranes of gram-negative bacteria
      and of mitochondrial porin or voltage-dependent anion channel (VDAC) in outer
      mitochondrial membranes (OMM) of eucaryotic cells was demonstrated about 15 years
      ago. However, the expression of VDAC in the plasmalemma (PLM) of transformed
      human B lymphoblasts has recently been indicated by cytotoxicity and indirect
      immunofluorescence studies. New data suggest that the expression of VDAC may be
      even more widespread. Different cell types express porin channels in their PLM
      and in intracellular membranes other than OMM. The functional expression of these
      channels may differ in the various compartments since recent experiments have
      demonstrated that the voltage dependence and ion selectivity of mitochondrial
      VDAC may be altered by their interaction with modulators. The present paper
      proposes a unifying concept for the ion-selective channels of cell membranes, in
      particular, those whose regulation is affected in cystic fibrosis.

PMID- 1380507
TI  - Toward the molecular structure of the mitochondrial channel, VDAC.
AB  - A summary is presented of the most recent information about the structure and
      mechanism of closure of the mitochondrial channel, VDAC. Considerable information
      has come from studies involving electron microscopy of two-dimensional crystals
      and from electrophysiological studies of wild-type channels and site-directed
      mutants. Available evidence points to a beta-barrel as the basic structural model
      for VDAC. Two models for voltage- or effector- induced closure have been
      proposed, the first involving removal of strands from the wall of the pore, the
      second invoking movement of protein domains into the lumen. Experimental
      strategies to resolve the actual mechanism are presented.

PMID- 1380509
TI  - Properties of the inner membrane anion channel in intact mitochondria.
AB  - The mitochondrial inner membrane possesses an anion channel (IMAC) which mediates
      the electrophoretic transport of a wide variety of anions and is believed to be
      an important component of the volume homeostatic mechanism. IMAC is regulated by
      matrix Mg2+ (IC50 = 38 microM at pH 7.4) and by matrix H+ (pIC50 = 7.7).
      Moreover, inhibition by Mg2+ is pH-dependent. IMAC is also reversibly inhibited
      by many cationic amphiphilic drugs, including propranolol, and irreversibly
      inhibited by N,N'-dicyclohexylcarbodiimide. Mercurials have two effects on its
      activity: (1) they increase the IC50 values for Mg2+, H+, and propranolol, and
      (2) they inhibit transport. The most potent inhibitor of IMAC is tributyltin,
      which blocks anion uniport in liver mitochondria at about 1 nmol/mg. The
      inhibitory dose is increased by mercurials; however, this effect appears to be
      unrelated to the other mercurial effects. IMAC also appears to be present in
      plant mitochondria; however, it is insensitive to inhibition by Mg2+, mercurials,
      and N,N'-dicyclohexylcarbodiimide. Some inhibitors of the adenine nucleotide
      translocase also inhibit IMAC, including Cibacron Blue, agaric acid, and
      palmitoyl CoA; however, atractyloside has no effect.

PMID- 1380510
TI  - Modulation of inner mitochondrial membrane channel activity.
AB  - Three classes of inner mitochondrial membrane (IMM) channel activities have been
      defined by direct measurement of conductance levels in membranes with patch clamp
      techniques in 150 mM KCl. The "107 pS activity" is slightly anion selective and
      voltage dependent (open with matrix positive potentials). "Multiple conductance
      channel" (MCC) activity includes several levels from about 40 to over 1000 pS and
      can be activated by voltage or Ca2+. MCC may be responsible for the Ca(2+)
      induced permeability transition observed with mitochondrial suspensions. A "low
      conductance channel" (LCC) is activated by alkaline pH and inhibited by Mg2+. LCC
      has a unit conductance of about 15 pS and may correspond to the inner membrane
      anion channel, IMAC, which was proposed from the results obtained from suspension
      studies. All of the IMM channels defined thus far appear to be highly regulated
      and have a low open probability under physiological conditions. A summary of what
      is known about IMM channel regulation and pharmacology is presented and possible
      physiological roles of these channels are discussed.

PMID- 1380511
TI  - Inhibition of angiogenesis in vitro and in ovo with an inhibitor of cellular
      protein kinases, MDL 27032.
AB  - Protein kinase C (PKC) was implicated as an important positive regulator of angio
      genesis by studies showing that tumor promoting phorbol esters, which activate
      PKC, stimulate angiogenesis both in vitro and in vivo. Therefore, inhibitors of
      PKC might be expected to block angiogenesis. MDL 27032 [4-propyl-5-(4-pyridinyl)
      2(3H)-oxazolone], an inhibitor of cellular protein kinases, prevented capillary
      like tube formation by human umbilical vein endothelial cells (HUVEC) on basement
      membrane preparations, an in vitro model for angiogenic activity. MDL 27032 had
      an IC50 = 50 microM, whereas MDL 27044, the 4-methyl analog of MDL 27032, was
      less effective (IC50 greater than 100 microM). This selectivity was reflected in
      the relative abilities of the two compounds to inhibit PKC and protein kinase A
      (PKA) activity prepared from HUVEC, and also to inhibit the basic fibroblast
      growth factor stimulated proliferation of HUVEC. MDL 27032 (0.3 microgram/egg)
      also significantly inhibited neovascularization in yolk sac membranes of
      developing chick embryos, whereas MDL 27044 added at concentrations up to 3
      micrograms/egg was not inhibitory when compared with vehicle treated controls.
      Adhesion of HUVEC to individual extracellular matrix proteins, including laminin,
      fibronectin, and fibrinogen, but not to the mixture of matrix components or
      collagen type I and IV, was inhibited after treatment with MDL 27032. These
      studies suggest that MDL 27032, may have potential as an anti-angiogenic agent
      because it disrupts both formation of tube-like structures by HUVEC on Matrigel
      and normal neovascularization in ovo. This inhibition may in part be due to
      altered cellular interactions with the extracellular matrix.

PMID- 1380512
TI  - Role of protein kinase C in transforming growth factor-beta 1 induction of
      carcinoembryonic antigen in human colon carcinoma cells.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) regulates the expression of the
      carcinoembryonic antigen (CEA) gene family in the human colon carcinoma cell line
      Moser. The mechanisms through which it acts, however, are unknown. In this
      communication, several lines of evidence are presented to show that the induction
      of CEA expression and secretion (collectively called CEA responses) by TGF-beta 1
      is associated with protein kinase C (PKC) pathway of signal transduction.
      Treatment of intact cells with the PKC-specific inhibitor calphostin C down
      modulated cellular PKC phosphotransferase activity and blocked the induction of
      the CEA responses by TGF-beta 1. Depletion of PKC by treatment of intact cells
      with phorbol ester also blocked the action of TGF-beta 1. The induction of the
      CEA responses by TGF-beta 1 was also blocked by the protein kinase inhibitor 1
      (isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), which also
      inhibited cellular PKC activity. However, TGF-beta 1 did induce the CEA responses
      in intact cells treated with the calmodulin antagonist N-(6-aminohexyl)-5-chloro
      1-naphthalenesulfonamide hydrochloride (W-7), the calmodulin-dependent
      phosphodiesterase inhibitor calmidazolium, the diacylglycerol kinase inhibitor
      R59 022, and the G-protein inhibitors cholera toxin and pertussis toxin.
      Treatment of intact cells with TGF-beta 1 induced a rapid and transient increase
      in PKC phosphotransferase activity. TGF-beta 1, however, was unable to induce PKC
      enzymatic activity in cells pretreated with calphostin C. Therefore, it is
      concluded that TGF-beta 1 regulates the CEA responses through a signal
      transducing pathway associated with PKC.

PMID- 1380513
TI  - Beta 1 integrins isolated from embryonic chicken fibroblasts bind to monomers and
      polymers of type I collagen.
AB  - The avian integrin beta 1 subfamily consists of multiple alpha-beta subunit
      heterodimers. We employed two different physical states of type I collagen,
      monomers and fibrils, in the isolation and characterization of avian collagen
      integrins. Affinity chromatography showed that three integrins, tentatively
      designated alpha 155 beta 1 (band 1), alpha 5a beta 1, and alpha 3 beta 1 (band
      2), bind fibrillar and monomeric collagen under physiological ionic conditions
      and require divalent cations for binding activity. Sodium chloride gradients (0
      0.5 M) were used to assess the functional ability of the integrins to remain
      bound to the two forms of type I collagen. The results show that integrins elute
      from the two forms of collagen with distinct fractionation profiles. One
      integrin, alpha 155 beta 1, binds fibrillar collagen with relatively higher
      affinity than the other beta 1 receptors. This same avian integrin, alpha 155
      beta 1, is immunoreactive with an antiserum (Hynes et al., 1989) raised against a
      peptide that corresponds to the entire alpha 5 cytoplasmic domain, and
      coincidently, part of the alpha 6 cytoplasmic domain (de Curtis et al., 1991).
      Cell biological studies employing double immunofluorescence show that integrins
      recognized by this antiserum co-localize with extracellular deposits of type I
      collagen.

PMID- 1380514
TI  - Induction of acetylcholine receptor clustering by native polystyrene beads.
      Implication of an endogenous muscle-derived signalling system.
AB  - Aneural muscle cells in culture often form acetylcholine receptor (AChR)
      clusters, termed hot spots, which are similar to those found at the postsynaptic
      membrane both in structure and in molecular composition. Although hot spots form
      on both dorsal and ventral surfaces of the cell, the ventral ones are better
      characterized because of their association with sites of cell-substratum contact.
      To understand the stimuli and mechanisms involved in ventral hot spot formation,
      native, uncoated polystyrene beads were applied to cultured Xenopus myotomal
      muscle cells to create local membrane-substratum contacts. These beads were able
      to induce a postsynaptic-type development as evidenced by the clustering of AChRs
      and the development of a set of ultrastructural specializations, including
      membrane infoldings and a basement membrane. Whereas these native beads were
      effective in inducing clustering, beads coated with bovine serum albumin or
      treated with serum-containing medium were ineffective. Native beads were also
      capable of inducing clusters in serum-free medium, indicating that their effect
      was mediated by endogenous molecules that were locally presented by the beads,
      rather than by bead adsorption of components in the medium. Heparan sulfate
      proteoglycan (HSPG) is a major component of the muscle extracellular matrix and
      our previous study has shown that basic fibroblast growth factor (bFGF), a member
      of the heparin-binding growth factor (HBGF) family, and its receptor are present
      in Xenopus myotomal muscle during the period of synaptogenesis. Therefore, we
      tested the involvement of HBGF in bead induction. The results of this study show
      the following: (1) preincubation of cultures in heparin, which solubilizes matrix
      bound HBGFs, suppressed the bead-induced AChR clustering. (2) Suramin, which
      interferes with the interaction between several growth factors and their
      receptors, also inhibited bead-induced clustering. (3) Tyrphostin, which blocks
      tyrosine kinase activity associated with a number of growth factor receptors, was
      also inhibitory to the bead effect. (4) The percentage of bead-induced AChR
      clusters was significantly enhanced by pretreating the cultures with bFGF prior
      to bead application. This exogenously applied bFGF could be largely removed by
      treatment of cultures with heparin, suggesting its association with HSPG at the
      cell surface. (5) An anti-bFGF neutralizing antiserum significantly reduced the
      efficacy of the bead stimulation. These data suggest that uncoated beads, which
      adhere to the cell surface and can mimic the cell-substratum interaction, effect
      a local presentation of HBGFs, such as bFGF, residing with the HSPG to their
      membrane receptors, thereby locally activating receptor-associated tyrosine
      kinases.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380515
TI  - Inhibition of nitric oxide synthesis increases focal ischemic infarction in rat.
AB  - We investigated whether inhibition of nitric oxide (NO) biosynthesis with N-omega
      nitro-L-arginine (NNA), a competitive inhibitor of NO synthase (NOS), would
      modify the volume of the focal ischemic infarction produced by occlusion of the
      middle cerebral artery (MCA) in spontaneously hypertensive rats. NNA was infused
      for 1 h (2.4 mg/kg/h) immediately following occlusion of the MCA. NNA increased
      lesion volume 24 h later by 32% over controls (150.8 +/- 16.6 to 199.2 +/- 17.4
      mm3; p less than 0.001, n = 6). This effect was antagonized by co-infusion of L-
      but not D-arginine. The antihypertensive rilmenidine (0.75 mg/kg) reduced the
      lesion by 27% (p less than 0.05, n = 4). Changes in lesion size were confined to
      the penumbra. NNA increased arterial pressure (AP) (118 +/- 8.9 to 149 +/- 16.0
      mm Hg; p less than 0.01, n = 3) but did not change regional CBF. However,
      elevation of AP did not change the lesion volume or distribution. We conclude
      that inhibition of the constitutive form of NOS in vivo increases the volume of
      focal ischemic infarction as a consequence of reduced NO biosynthesis. The
      absence of NO availability may extend lesion formation by inhibition of reactive
      hyperemia, platelet disaggregation, and/or release of neuroprotective
      neuromodulators in the penumbra, which may counteract and override any of its
      neurotoxic actions.

PMID- 1380516
TI  - Area 3a in the cat. I. A reevaluation of its location and architecture on the
      basis of Nissl, myelin, acetylcholinesterase, and cytochrome oxidase staining.
AB  - Current knowledge on the anatomy of area 3a of the cat mainly derives from the
      cyto- and myeloarchitectonic study of Hassler and Muhs-Clement (J Hirnforsch
      6:377, 1964). Previous investigations in the cat had failed to identify a
      cortical region comparable to monkey's area 3a. In the present study, Nissl,
      myelin, acetylcholinesterase, and cytochrome oxidase staining techniques were
      applied to coronal and sagittal serial sections of the cat brain. Area 3a appears
      as a slender band of cortex between areas 4 and 3b, and in Nissl-stained sections
      it is mainly characterized by an attenuated granular layer IV, overlying a thin
      layer V with pyramidal cells of various sizes, including a few large ones. These
      cytoarchitectonic features are sufficient to differentiate area 3a from
      neighboring areas, although the borders between them are not sharp in many cases.
      After the Nissl staining, the acetylcholinesterase staining proved to be the most
      helpful in defining the structure and borders of area 3a. Acetylcholinesterase
      staining was dense in layer I (in contrast with a lighter staining of outer layer
      I in area 4), and light in layers II and IIIa, changing to moderate in IIIc and
      IV (a pattern which is accentuated in area 3b). Myelin and cytochrome oxidase
      techniques also yielded differential staining patterns of area 3a and neighboring
      areas 4 and 3b, although the borders were not easily drawn with these techniques.
      Whereas our cyto- and myeloarchitectonic findings were comparable to those of
      Hassler and Muhs-Clement ('64) and applied well to area 3a in the convexity of
      the hemisphere, we found that most of the area 3a described by these authors in
      the medial face of the hemisphere had a number of distinguishing architectonic
      (as well as connectional and physiological) features which enabled us to define
      it as a separate area (7m). The techniques we used to delineate area 3a are
      compatible with most current procedures of histo- and immunohistochemical
      staining of the brain, and may also provide valuable supporting data for
      electrophysiological studies.

PMID- 1380517
TI  - The striatum and the globus pallidus send convergent synaptic inputs onto single
      cells in the entopeduncular nucleus of the rat: a double anterograde labelling
      study combined with postembedding immunocytochemistry for GABA.
AB  - The entopeduncular nucleus is one of the major output stations of the basal
      ganglia. In order to better understand the role of this structure in information
      flow through the basal ganglia, experiments have been performed in the rat to
      examine the chemical nature, morphology, and synaptology of the projections from
      the globus pallidus and striatum to the entopeduncular nucleus. In order to
      examine the morphology and synaptology of pallidoentopeduncular terminals and
      striatoentopeduncular terminals, rats were subjected to a double anterograde
      labelling study. The globus pallidus was injected with Phaseolus vulgaris
      leucoagglutinin (PHA-L), and on the same side of the brain, the striatum was
      injected with biocytin. The entopeduncular nuclei of these animals were then
      examined for anterogradely labelled pallidal and striatal terminals. Rich
      plexuses of PHA-L-labelled pallidal terminals and biocytin-labelled striatal
      terminals were identified throughout the entopeduncular nucleus. At the electron
      microscopic level, the pallidal boutons were classified as two types. The
      majority (Type 1), were large boutons that formed symmetrical synapses with the
      dendrites and perikarya of neurones in the entopeduncular nucleus. Type 2 PHA-L
      labelled terminals were much rarer, slightly smaller, and formed asymmetrical
      synapses. It is suggested that the Type 2 boutons are not derived from the globus
      pallidus but from the subthalamic nucleus. The biocytin-labelled terminals from
      the striatum had the typical morphological features of striatal terminals and
      formed symmetrical synapses. The distribution of the postsynaptic targets of the
      pallidal terminals and the striatal terminals differed in that the pallidal
      terminals preferentially made synaptic contact with the more proximal regions of
      the neurones in the entopeduncular nucleus, whereas the striatal terminals were
      located more distally on the dendritic trees. Examination in the electron
      microscope of areas where there was an overlap of the two sets of anterogradely
      labelled boutons revealed that terminals from the globus pallidus and the
      striatum made convergent synaptic contact with the perikarya and dendrites of
      individual neurones in the entopeduncular nucleus. In order to examine the
      chemical nature of the input to the entopeduncular nucleus from the globus
      pallidus and the striatum, ultrathin sections were immunostained by the
      postembedding method to reveal endogenous GABA. Three classes of GABA-containing
      terminals were identified; two of them formed symmetrical synapses and one rare
      type formed asymmetrical synapses. The combination of the GABA
      immunocytochemistry and anterograde labelling revealed that both the striatal and
      pallidal afferents that make symmetrical synapses with neurones in the
      entopeduncular nucleus, including those involved in convergent inputs, are
      GABAergic.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380518
TI  - Afferent projections to the cholinergic pedunculopontine tegmental nucleus and
      adjacent midbrain extrapyramidal area in the albino rat. I. Retrograde tracing
      studies.
AB  - The afferent connections of the pedunculopontine tegmental nucleus (PPT) and the
      adjacent midbrain extrapyramidal area (MEA) were examined by retrograde tracing
      with wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). Major
      afferents to the PPT originate in the periaqueductal gray, central tegmental
      field, lateral hypothalamic area, dorsal raphe nucleus, superior colliculus, and
      pontine and medullary reticular fields. Other putative inputs originate in the
      paraventricular and preoptic hypothalamic nuclei, the zona incerta, nucleus of
      the solitary tract, central superior raphe nucleus, substantia innominata,
      posterior hypothalamic area, and thalamic parafascicular nucleus. The major
      afferent to the medially adjacent MEA originates in the lateral habenula, while
      other putative afferents include the perifornical and lateral hypothalamic area,
      periaqueductal gray, superior colliculus, pontine reticular formation, and dorsal
      raphe nucleus. MEA inputs from basal ganglia nuclei include moderate projections
      from the substantia nigra pars reticulata, entopeduncular nucleus, and a small
      projection from the globus pallidus, but not the subthalamic nucleus. Dense
      anterograde labeling was observed in the substantia nigra pars compacta,
      entopeduncular nucleus, subthalamic nucleus, globus pallidus, and caudate-putamen
      only following WGA-HRP injections involving the MEA. The results of this study
      demonstrate that the PPT and MEA share many potential afferents. Remarkable
      differences were found that support distinguishing between these two nuclei in
      future studies regarding the functional organization of the midbrain and pons.
      The results, for example, confirm our previous observations that the largely
      reciprocal connections between the midbrain and basal ganglia distinguish the MEA
      from the PPT. Afferents from the lateral habenula and contralateral superior
      colliculus represent extensions of more traditional basal ganglion circuitry
      which further delineate the MEA from the PPT. The results are discussed with
      respect to the important role of the midbrain and pons in behavioral state
      control and locomotor mechanisms.

PMID- 1380519
TI  - Pathway from the zona incerta to the superior colliculus in the rat.
AB  - In order to test the proposal that the zona incerta contributes to the generation
      of orienting movements, we examined the synaptic relationships between the
      incertotectal pathway and the cells of origin of the predorsal bundle. The
      predorsal bundle cells give rise to the major premotor pathway from the superior
      colliculus to the brainstem gaze centers. First, cytochrome oxidase
      histochemistry, gamma-aminobutyric acid (GABA), and glutamic acid decarboxylase
      (GAD) immunocytochemistry, and the axonal transport of markers were used to
      define the borders of a ventral subdivision of the zona incerta. This subdivision
      projects topographically to the same sublamina of the intermediate grey layer of
      the superior colliculus that contains the vast majority of the predorsal bundle
      cells. Experiments in which incertotectal cells were labeled by both retrograde
      transport and immunocytochemistry showed that this pathway is GABAergic.
      Retrograde and anterograde experiments also showed that this pathway is
      reciprocated by a pathway from the intermediate grey layer of the superior
      colliculus to the same ventral subdivision of the zona incerta. Finally,
      experiments combining axonal transport and electron microscopic methods showed
      that the incertotectal pathway is the source of a monosynaptic GABAergic input to
      the cells of origin of the predorsal bundle. The ventral subdivision of the zona
      incerta is contrasted with a second source of GABAergic input to the predorsal
      bundle cells, the substantia nigra pars reticulata.

PMID- 1380520
TI  - Progressive morphological abnormalities observed in rat spinal motor neurons at
      extended intervals after axonal regeneration.
AB  - It is generally accepted that mammalian spinal motor neurons return to normal
      after axotomy if their regenerated axons successfully reinnervate appropriate
      peripheral targets. However, morphological abnormalities, recently observed in
      spinal motor neurons examined 1 year after nerve crush injury, raise the
      possibility that delayed perikaryal changes occur after regeneration is complete.
      In order to distinguish between chronic and progressive alterations in neurons
      with long-term regenerated axons, rat spinal motor neurons and dorsal root
      ganglion cells were examined at 5 and 10 months following unilateral sciatic
      nerve crush. Neurons with regenerated axons were identified by retrograde
      labelling with horseradish peroxidase. The structural properties of neurons
      ipsilateral to nerve injury were compared to those of neurons from the spinal
      cord and dorsal root ganglia on the contralateral side and from age-matched
      control rats. At 5 months postcrush, the morphology of motor and sensory neurons
      ipsilateral to injury was comparable to that of control cells. However, several
      features of the motor neurons with regenerated axons distinguished them from
      control motor neurons at 10 months postcrush. Mean perikaryal area of ipsilateral
      spinal motor neurons was larger than the means for control motor neurons (p less
      than .001). Ipsilateral spinal motor neurons also appeared clustered within the
      spinal cord and had thicker dendrites. Dorsal root ganglion cells with
      regenerated axons were slightly larger than control cells at 10 months postcrush
      but they exhibited no other morphological changes. The present findings indicate
      that spinal motor neurons are progressively altered after their regenerated axons
      have reestablished functional synapses with their peripheral targets.

PMID- 1380521
TI  - Effect of neonatal degranulation on the morphological development of rat CA3
      pyramidal neurons: inductive role of mossy fibers on the formation of thorny
      excrescences.
AB  - Intracellular peroxidase injections were made on CA3 pyramidal neurons from
      slices obtained from 3-60 day old control and experimental rats. Experimental
      rats had been irradiated at birth with gamma-rays to destroy the granule cells of
      the fascia dentata. Neonatal gamma-ray irradiation induced a clear cut reduction
      of the total number of granule cells (80% decrease at P60) and mossy fibers as
      revealed by Nissl and Timm stains. The number of branching points and segments,
      total dendritic length, and density of dendritic spines in the stratum radiatum
      and stratum oriens on CA3 pyramidal cells were not significantly different
      between control and irradiated rats. To quantify the development of thorny
      excrescences we measured the number and total area of the thorny excrescences per
      neuron at different stages of development. gamma-Ray irradiation induced a
      reduction in the number and total area of thorny excrescences. This effect was
      readily apparent by postnatal day (P) 12, and a reduction of 70% in the total
      area was observed at P30. In conclusion, gamma-ray irradiation destroys the
      majority of granule cells and induces a reduction in the development of thorny
      excrescences. Our data strongly suggest that this effect is directly caused by
      the lack of mossy fibers rather than by the irradiation itself since other
      parameters (i.e., the number of segments and branching points, density of non
      mossy spines, and total dendritic length) were not affected. Therefore, we
      suggest that mossy fibers play an inductive role in the formation of thorny
      excrescences.

PMID- 1380522
TI  - Ventral pallido-striatal pathway in the rat brain: a light and electron
      microscopic study.
AB  - Most theories of basal ganglia functions have been based on a model circuit in
      which the flow of information follows a one-way loop proceeding from the cerebral
      cortex to the striatum, the pallidum/nigra, the thalamus, and then returns to the
      cortex. However, this model neglects data from several studies that show a direct
      feedback projection from the pallidum to the striatum. In this study, we have
      examined this feedback connection in the ventral striopallidal system to
      determine the morphology and chemical properties of ventral pallido-striatal
      projection neurons and to determine the morphology of ventral pallidal efferents
      in the ventral striatum. Fluoro Gold was injected into the ventral striatum to
      retrogradely label ventral pallidal projection neurons. Substance P
      immunoreactivity was used as a pallidal marker to delineate the ventral pallidum.
      The results show that most neurons retrogradely labeled by Fluoro Gold lie in the
      ventral pallidum. Additional double-labeling experiments show that none of these
      Fluoro Gold-labeled cells are cholinergic neurons; however, some are
      immunoreactive for parvalbumin, a calcium-binding protein found in many pallidal
      neurons. Electron microscopy revealed that the somata and dendrites of these
      labeled ventral pallidal projection neurons form many synapses with unlabeled
      terminals. Injection of Phaseolus vulgaris-leucoagglutinin into the ventral
      pallidum anterogradely labeled many fibers in the ventral striatum. Electron
      microscopy revealed that these labeled axons form both symmetric and asymmetric
      synapses with ventral striatal neurons. We have thus confirmed that there is a
      significant direct projection from the ventral pallidum to the ventral striatum.
      Whether this projection forms a part of either monosynaptic or polysynaptic
      feedback loops remains to be clarified. Nevertheless, this pallidostriatal
      projection must be integrated into the theories on basal ganglia functions.

PMID- 1380523
TI  - The influence of inhibitory afferents on the development of postsynaptic
      dendritic arbors.
AB  - The growth and maintenance of dendritic form is dependent on normally functioning
      excitatory afferents. We have now examined the development of dendritic arbors in
      the gerbil lateral superior olive (LSO), following contralateral cochlear removal
      at postnatal day 7, a manipulation that substantially eliminates driven
      inhibitory transmission. Previous studies have demonstrated that the morphology
      of LSO dendritic arbors varies with tonotopic position and becomes more
      restricted with age. The presumed decrease of inhibitory transmission in the
      contralateral LSO resulted in a hypertrophic response. Quantification of Golgi
      impregnated neurons revealed that dendrites had a significantly greater number of
      branch points, and their arbors were more spread out along the frequency axis
      compared to normal. This was especially apparent in the high frequency projection
      region where the glycine receptor density is known to be 4-fold higher than in
      the low frequency projection region. A measure of LSO nucleus size, cross
      sectional area, was identical to control values, indicating no overt signs of
      degenerative phenomena. Cochlear ablation resulted in a significant atrophy of
      the ipsilateral LSO, with significant effects on dendritic structure. We conclude
      that decreased inhibitory transmission during development does not lead to a net
      degenerative response. Rather, the postsynaptic neurons exhibit a hypertrophic
      phenotype that may be due to the persistence of an immature state. These results
      indicate that activity-dependent morphogenetic events are a consequence of both
      excitatory and inhibitory synaptic transmission.

PMID- 1380524
TI  - Transneuronal labeling of cochlear nucleus neurons by HRP-labeled auditory nerve
      fibers and olivocochlear branches in mice.
AB  - Auditory nerve fibers were labeled by extracellular injections of horseradish
      peroxidase into the spiral ganglion in mice. The labeled fibers were traced in an
      anterograde direction through the auditory nerve into the cochlear nucleus. In
      almost half of the injections, the labeled endings of auditory nerve fibers
      contacted cochlear nucleus neurons that were also labeled with horseradish
      peroxidase and were presumably transneuronally labeled. Only darkly labeled
      endings were associated with transneuronally labeled neurons, but not all darkly
      labeled endings had targets that were transneuronally labeled. Transneuronal
      labeling occurred almost exclusively in the ventral cochlear nucleus, often
      between endbulbs and bushy cells. Both "modified" endbulbs and the larger
      endbulbs of Held transneuronally labeled the bushy cells that they contacted. At
      the ultrastructural level, transneuronal labeling was evident as a darkening of
      ribosomes and the membrane surfaces of mitochondria, endoplasmic reticulum, and
      the nucleus. Transneuronal labeling occurred rarely in octopus, small, and
      stellate cells, and in neurons of the dorsal cochlear nucleus. Spiral ganglion
      injections also label olivocochlear fibers, efferent fibers that pass through the
      ganglion en route to the hair cells. These fibers give off branches to the
      cochlear nucleus that were rarely associated with transneuronal labeling. In
      eight instances, the targets of olivocochlear branches were stellate cells or
      small cells. We suggest that in our mouse preparation, horseradish peroxidase is
      effective as a transneuronal marker because the short distance from injection
      site to the cochlear nucleus results in a high concentration of horseradish
      peroxidase in the endings of the auditory nerve fibers.

PMID- 1380525
TI  - Immunolocalization of integrin alpha 6 beta 4 in mouse junctional epithelium
      suggests an anchoring function to both the internal and the external basal
      lamina.
AB  - The localization of the integrin alpha 6 beta 4, a transmembrane adhesion
      molecule associated with hemidesmosomes, was studied in mouse junctional
      epithelium (JE) by the use of monoclonal antibodies in indirect
      immunofluorescence microscopy. The results showed that the integrin a6 subunit
      was expressed throughout the JE and was localized to the cell membranes,
      including the aspects facing the internal and external basal laminae. The beta 4
      subunit had a more restricted distribution. It was expressed only in cells facing
      the internal and the external basal laminae and had a basally polarized
      distribution. In other parts of gingival epithelium, both integrin subunits were
      mainly expressed at the basal aspects of basal epithelial cells. The basement
      membrane components, type IV collagen and laminin, could be detected only in the
      external basal lamina and in other basement membranes of gingival epithelium. The
      results indicate that the a6 beta 4 integrin, expressed in mouse JE, has a role
      in mediating the attachment of the cells to the basement membranes facing the
      connective tissue and the tooth.

PMID- 1380526
TI  - Long-term follow-up of hepatitis B chronic carriers who responded to interferon
      therapy.
AB  - We studied the long-term outcome of patients with chronic hepatitis B virus (HBV)
      infection who responded to interferon (IFN) therapy. Between 1983 and 1988, 120
      patients were included in 5 different protocols; 94 patients were treated with
      IFN and 26 were controls. Loss of serum HBV-DNA was considered a partial response
      and occurred in 34 of the treated patients and in 10 of the controls. Only the
      partial-response patients were followed up for 14-64 months (mean 46 months).
      HBeAg disappeared in 32/34 of the partial-response treated patients and in 9/10
      of the controls. During the follow-up period, 6/34 (18%) treated patients and
      1/10 controls suffered a reactivation of the disease with reappearance of HBV
      DNA. Only 8/34 (23%) treated patients and 1/10 of the controls lost HBsAg; no
      statistical differences were observed in baseline characteristics between HBsAg
      negative patients and patients who remained HBsAg-positive. Of eight HBsAg
      negative treated patients, four were serum HBV-DNA-negative upon polymerase chain
      reaction and thus formed the HBsAg-negative control cases. Although the frequency
      of HBsAg loss in treated patients is relatively low, the improvement in liver
      disease obtained from IFN therapy is sustained over a long period.

PMID- 1380527
TI  - Demonstration of peptide-specific and cross-reactive epitopes in proteins
      reacting with antimitochondrial antibodies of primary biliary cirrhosis.
AB  - Recently the main targets of antimitochondrial antibodies (AMA) of primary
      biliary cirrhosis have been identified as parts of three related mitochondrial
      multienzyme complexes, namely pyruvate dehydrogenase (PDH), branched chain alpha
      ketoacid dehydrogenase (BKDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH).
      Usually AMA-positive PBC serum samples show reactivity to more than one of these,
      raising the question whether they are exclusively different antibodies or are, at
      least in part, the result of cross-reactive specificities. With Western
      immunoblotting, four antigens with molecular masses of 74, 52, 51 and 43 kDa, are
      recognized by PBC sera. In this study, using affinity purified antibodies from
      mitochondrial proteins immobilized on nitrocellulose blots, we demonstrate the
      presence of peptide-specific and cross-reactive epitopes in some targets. In
      particular, at least three different epitopes present in the 74-kDa protein
      (presumed to by PDH-E2) are also present in the 51-kDa protein (probably PDH-X),
      and two in the 52-kDa peptide (possibly BCKDH-E2). Moreover, the 43-kDa
      mitochondrial protein (the identity of which is more problematic) has three
      epitopes. One of these is also present in the 74-, 52- and 51-kDa proteins, a
      second in the 74- and 51-kDa, and a third seems to be peptide-specific. These
      results show that different sera with the same immunoblotting pattern of
      reactivity can have antibodies with different antigenic specificities and,
      conversely, that the same specificity can be responsible for more than one band.

PMID- 1380528
TI  - Post-embedding staining with high-iron diamine-thiocarbohydrazide-silver
      proteinate and its application to visualizing sulfated glycoconjugates in
      cryofixed kidney and cartilage.
AB  - Cryofixation is generally believed to provide optimal tissue preservation.
      However, certain post-embedding cytochemical reactions, such as high-iron diamine
      (HID) staining for sulfated glycoconjugates, are not applicable to cryofixed and
      freeze-substituted tissues. In the present study, the HID technique was therefore
      adapted for post-embedding staining. HID staining was performed on thin sections
      of chemically and cryofixed kidney and growth plate cartilage, embedded in Epon
      and various acrylic-based resins. All resins and most tissue preparation
      conditions allowed post-embedding staining with HID, albeit to variable degrees.
      However, no significant cytochemical reaction was obtained with tissue sections
      of osmicated kidney embedded in Epon. Profile views of re-embedded sections
      showed that large stain deposits were usually restricted to the surface, whereas
      small ones were observed throughout the entire thickness of the section. The
      staining pattern was essentially similar between chemically fixed and cryofixed
      specimens. In the glomerulus, stain deposits were mainly seen over the free
      surface of podocyte foot processes and over the lamina rara externa. The
      pericellular cartilage matrix of chemically fixed specimens often appeared as
      condensed elements, usually stained with large deposits. In cryofixed tissues
      this matrix formed a meshwork composed of thin, extended filamentous structures,
      many of which showed linear arrays of smaller stain deposits. The data presented
      here indicate that post-embedding HID-TCH-SP staining can be successfully
      performed on thin sections of tissues embedded in various resins and, as a
      result, can be further adapted to cryo-prepared specimens to give a high
      resolution localization of sulfated glycoconjugates in tissues with optimal
      molecular preservation.

PMID- 1380529
TI  - Differential expression of proline-rich proteins in rabbit salivary glands.
AB  - Salivary glands synthesize and secrete an unusual family of proline-rich proteins
      (PRPs) that can be broadly divided into acidic and basic PRPs. We studied the
      tissue-specific expression of these proteins in rabbits, using antibodies to
      rabbit acidic and basic PRPs as well as antibodies and cDNA probes to human PRPs.
      By immunoblotting, in vitro translation, and Northern blotting, basic PRPs could
      be readily detected in the parotid gland but were absent in other salivary
      glands. In contrast, synthesis in vitro of acidic PRPs was detected in parotid,
      sublingual, and submandibular glands. Ultrastructural localization with
      immunogold showed heavy labeling with antibodies to acidic PRPs of secretory
      granules of parotid acinar cells and sublingual serous demilune cells. Less
      intense labeling occurred in the seromucous acinar cells of the submandibular
      gland. With antibodies to basic PRPs, the labeling of the parotid gland was
      similar to that observed with antibodies to acidic PRPs, but there was only weak
      labeling of granules of a few sublingual demilune cells, and no labeling of the
      submandibular gland. These results demonstrate a variable pattern of distribution
      of acidic and basic PRPs in rabbit salivary glands. These animals are therefore
      well suited for study of differential tissue expression of PRPs.

PMID- 1380530
TI  - Plasmodium falciparum-infected erythrocyte receptor(s) for CD36 and
      thrombospondin are restricted to knobs on the erythrocyte surface.
AB  - Adherence of Plasmodium falciparum-infected RBCs (PRBC) to endothelial cells
      causes PRBC sequestration in cerebral microvessels and is considered to be a
      major contributor to the pathogenesis of cerebral malaria. Both CD36 and
      thrombospondin (TSP) are glycoproteins that mediate PRBC adherence to endothelial
      cells in vitro. Because they are both expressed on the surface of endothelial
      cells, they probably contribute to PRBC sequestration and vascular occlusion in
      vivo. By applying affinity labeling of receptor binding sites with purified
      ligands, we showed for the first time that both CD36 and TSP can bind
      independently to the PRBC surface and that the PRBC receptor(s) for CD36 and TSP
      are localized specifically to the electron-dense knob protrusions of the PRBC
      surface. These findings may help in efforts to develop a malaria vaccine to
      prevent cerebral malaria.

PMID- 1380531
TI  - Superantigen-mediated human monocyte-T lymphocyte interactions are associated
      with an MHC class II-, TCR/CD3-, and CD4-dependent mobilization of calcium in
      monocytes.
AB  - The present study was designed to examine the potential involvement of calcium
      ions as second messengers in the mediation of the staphylococcal enterotoxin A
      (SEA)/MHC class II-induced activation of human monocytes. Treatment of monocytes
      with a monomeric form of SEA failed to induce detectable changes in the level of
      intracellular calcium in either monocytes or THP-1 cells. However, cross-linking
      of SEA with biotin-avidin induced a rapid and transient increase in calcium
      levels in monocytes and in INF-gamma-treated THP-1 cells. This artificial cross
      linking system was reproduced by natural physiologic ligands expressed on the
      surface of T lymphocytes. Delayed, transient, and concentration (cell as well as
      toxin)-dependent increases in the cytoplasmic level of free calcium in SEA
      treated monocytes were observed upon the addition of autologous resting T cells
      or purified CD4+ cells, but not of CD8+ cells, B cells, or neutrophils.
      Antibodies against MHC class II Ag, TCR/CD3, and CD4 molecules inhibited the SEA
      dependent interaction between monocytes and T cells as indicated by significant
      decreases in the rise of calcium levels observed in monocytes. Anti-CD8 and anti
      class I antibodies did not affect the interaction between the monocytes and the T
      cells and failed to alter the calcium response. Taken together, these results
      suggest that the SEA-induced, T cell-dependent calcium mobilization in monocytes
      requires physical interactions between SEA-MHC class II, TCR/CD3, and CD4
      molecules. The ability to mediate a T cell-dependent calcium increase in
      monocytes was shared by several enterotoxins including staphylococcal enterotoxin
      B and toxic shock syndrome toxin-1. The characteristics of the SEA-mediated
      calcium mobilization in monocytes strongly support the hypothesis that this
      response is an integral part of the signal transducing machinery linked to MHC
      class II molecules.

PMID- 1380532
TI  - In vivo induced allo-reactive natural killer cells.
AB  - We have previously shown that rat allo-selective cells of the CD2+CD5- phenotype
      were generated in Brown Norway (BN) rats after immunization with allogeneic
      Wistar/Furth (WF) cells, whereas immunization with semi-allogeneic F1 (WF/BN)
      cells generated CD2+CD5+ effector T cells. We now report that the allo-selective
      CD2+CD5- lymphocytes lacked expression of intact CD3 complexes and expressed NKR
      P1 molecules although lower as compared to classical NK cells, implicating that
      these lymphocytes constitute a subset of NK cells. The CD5+ T cells were not
      cytolytically active in BN rats immunized with WF cells indicating an intersubset
      regulation with mutually exclusive activation of either allo-selective T cells or
      allo-selective NK cells. Cold target inhibition showed that lysis of both
      allogeneic target cells and NK-sensitive target cells was mediated by the same
      NKR-P1 intermediate effector cells. These NK cells lysed WF but not allogeneic
      Fischer 344 or autologous BN target cells, indicating selective recognition of an
      allogeneic determinant. Semiallogeneic F1 (WF/BN) target cells were not lysed.
      Furthermore, target cells from F1 (WF/BN) x WF back-cross hybrids lacking
      expression of RT1n (self-MHC class I) were susceptible to lysis, whereas back
      cross hybrids expressing RT1n were protected from lysis, indicating that self-MHC
      molecules conferred protection from lysis. These findings implicate the existence
      of NKR-P1intermediate and NKR-P1high NK cell subsets with different regulation
      and function in vivo.

PMID- 1380533
TI  - The CD28 ligand, B7, enhances IL-2 production by providing a costimulatory signal
      to T cells.
AB  - Previous studies demonstrated that a human pre-B acute lymphoblastic leukemia
      cell line, NALM-6, failed to stimulate a primary MLR, despite expression of class
      II MHC and adhesion molecules. Here we demonstrate that this is the result of the
      fact that NALM-6 cells do not express the ligand for CD28, namely B7. NALM-6
      transfectants that expressed high levels of B7 gained the capacity to stimulate
      IL-2 production by class II MHC molecule-specific alloreactive T cells and to
      costimulate a polyclonal population of purified T cells cultured with immobilized
      anti-CD3 mAb. In the presence of PMA, NALM-6 cells transfected with B7
      polyclonally stimulated T cells in a cyclosporine A-resistant fashion, a property
      previously attributed only to agonistic anti-CD28 mAb. The gain of these
      functions could not be explained solely by an increased capacity of the
      transfectants to form conjugates with T cells, suggesting that the CD28/B7
      interaction transduces a costimulatory signal in T cells.

PMID- 1380534
TI  - Activation-driven T cell death. II. Quantitative differences alone distinguish
      stimuli triggering nontransformed T cell proliferation or death.
AB  - Clonal deletion is the major mechanism by which T cell tolerance is achieved in
      vivo. The process of activation-driven cell death, originally characterized with
      T cell hybridomas, likely represents the mechanism of clonal deletion because it
      shares a number of properties with the in vivo process, especially the ability to
      be triggered in an Ag-specific manner, the cell-autonomous nature of the
      response, and its sensitivity to the drug cyclosporin A. We now have extended our
      analysis of activation-driven cell death to clonal populations of nontransformed
      T cells. Activation-driven cell death can be induced in nontransformed T
      lymphocytes by combinations of mitogenic stimuli. In particular, two mitogenic
      stimuli at high dose, one a lymphokine and the other delivered via the TCR or
      another activation structure, are required to induce activation-driven cell
      death. Activation-driven cell death is an active cell suicide process with
      attributes typical of physiological cell death, including early nuclear
      disintegration and a requirement for macromolecular synthesis, and is distinct
      from death by factor deprivation. Susceptibility to the induction of cell death
      by antigenic or activating stimulation is a common aspect of most T cells and is
      consistent with observations that clonal deletion can occur throughout T cell
      ontogeny. Most importantly, the alternative cellular responses of cell death and
      cell proliferation in nontransformed T cells appear to be triggered solely as a
      function of quantitative differences in the doses of identical stimuli. This can
      be viewed as a dose-dependent switch that determines cell fate. Developmental
      regulation of this switch may explain the processes of positive and negative
      selection during T cell ontogeny and also provide a mechanistic rationale for a
      strategy of selective anti-tumor therapy.

PMID- 1380535
TI  - A single amino acid mutation in CDR3 of the 3-14-9 L chain abolished expression
      of the IDA 10-defined idiotope and antigen binding.
AB  - The ABPC 48 myeloma protein and the 3-14-9 mAb derive their V region genes from
      the same VH and V kappa gene families. They also share a cross-reactive idiotope
      defined by the anti-Id mAb IDA 10. Whereas ABPC 48 is specific for bacterial
      levan, 3-14-9 showed a significant Ag-binding activity to aminophenyl-beta-N
      acetylglucosaminide (AZO). In order to define the molecular basis of idiotope
      expression and Ag-binding activity, we have cloned the genes encoding the 3-14-9
      H and L chain V region genes, generated antibodies that carry mutations within
      the L chain genes, by site-directed mutagenesis, and investigated the effects of
      those mutations with respect to IDA 10 idiotope expression and binding to AZO.
      Our findings show that, whereas expression of the IDA 10-defined idiotope
      requires association of both the H and L chains, a single change (glycine to
      phenylalanine) at position 91 in the third complementarity-determining region of
      the L chain abolished both idiotope expression and Ag-binding activity. In
      addition, a L chain change of alanine to threonine at position 25 allowed
      idiotope expression to some extent but significantly reduced binding activity to
      AZO. These data suggest that a single amino acid change can play a crucial role
      in the functional activity and structural integrity of antibodies.

PMID- 1380536
TI  - Multiple hemopoietic growth factors stimulate activation of mitogen-activated
      protein kinase family members.
AB  - Stimulation of hemopoietic cells with IL-3, IL-4, IL-5, granulocyte-macrophage
      CSF and Steel factor-(SLF) induced tyrosine phosphorylation of a number of
      protein substrates. Two of these proteins, designated p42 and p44, were tyrosine
      phosphorylated rapidly in response to treatment with IL-3, IL-5, granulocyte
      macrophage-CSF and SLF, but not IL-4. We demonstrate that these common substrates
      are members of the mitogen-activated protein kinase (MAP kinase) family of
      protein serine/threonine kinases. Ion-exchange chromatography yielded a peak of
      MAP kinase activity eluting at 0.3 to 0.32 M NaCl. Immunoblotting of column
      fractions with antiphosphotyrosine antibodies showed coelution of the peak of MAP
      kinase enzyme activity with the p42 and p44 tyrosine phosphorylated species, and
      with two proteins of 42 and 44 kDa which were immunoreactive with anti-MAP kinase
      antibodies. Moreover, a characteristic shift in mobility of the p42 and p44
      species was observed after factor treatment. Time-course analyses and subsequent
      ion-exchange chromatography demonstrated SLF activation of MAP kinase activity
      was maximal after 2 min of factor treatment and decreased to basal levels after
      30 min stimulation. By contrast, activation of MAP kinase after IL-5 treatment
      was not as rapid. Maximal activity was observed 15 min after stimulation and
      remained elevated for up to 60 min after IL-5 addition. Investigation of the role
      of protein kinase C in the mechanism of activation by these growth factors
      demonstrated that specific inhibition of protein kinase C led to a reduction, but
      not ablation, of the SLF and IL-3 induced stimulation of MAP kinase activity. The
      use of synthetic peptide substrates confirmed SLF and IL-5 activate isoforms of
      MAP kinases. These results demonstrate that members of the MAP kinase family are
      involved in common signal transduction events elicited by IL-3, IL-5, granulocyte
      macrophage-CSF and Steel factor, but not those involving IL-4.

PMID- 1380537
TI  - Human recombinant soluble decay accelerating factor inhibits complement
      activation in vitro and in vivo.
AB  - Complement plays a role in activating the inflammatory response and has been
      implicated in the pathogenesis of some inflammatory diseases. With a view toward
      controlling unwanted C activation, we evaluated the C regulator, human decay
      accelerating factor (DAF). Three forms of recombinant DAF were purified from
      transfected Chinese hamster ovary cells: glycophosphatidylinositol (GPI)-linked
      membrane DAF (mDAF) extracted from cell membranes; spontaneously shed soluble DAF
      (sDAF) derived from mDAF; and a novel secreted protein (seDAF), generated by
      deletion of the signal for GPI attachment. We show that all three molecules
      inhibit both the classical and alternative pathways of C activation. The
      following observations indicate that mDAF extracted from Chinese hamster ovary
      cells reincorporates into RBC membranes via its GPI anchor: 1) cells that are
      preincubated with mDAF and then washed remain fully protected from C-mediated
      hemolysis; 2) incubation with phosphatidylinositol-specific phospholipase C
      abolishes this protection; and 3) sDAF and seDAF, which lack a GPI anchor, do not
      associate with cell membranes. mDAF is a more potent inhibitor of C-mediated
      hemolysis than either sDAF or seDAF, suggesting that incorporation into cell
      membranes greatly enhances the efficiency with which DAF inhibits C activation on
      the cell surface. In contrast, C activation in the fluid phase is inhibited by
      sDAF and seDAF, but not by mDAF, possibly due to interference by serum
      lipoproteins. A reversed passive Arthus reaction in guinea pigs was used to
      evaluate the ability of recombinant seDAF to inhibit C activation in vivo. When
      administered at dermal sites, seDAF reduced the severity of immune complex
      mediated inflammatory reactions induced by a reversed passive Arthus reaction, as
      judged by both gross and histologic examination. These data indicate that seDAF
      may be useful as an anti-inflammatory therapeutic.

PMID- 1380538
TI  - Decay-accelerating factor functions as a signal transducing molecule for human
      monocytes.
AB  - Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol-anchored
      membrane protein that protects cells from damage by autologous complement
      activation. Of the four mAb against DAF prepared in our laboratory, 1C6
      completely blocked DAF function, whereas 5B2 partially blocked it. Using these
      mAb, we investigated whether human monocytes were activated via DAF molecules.
      When monocytes were incubated with 1C6 alone, glucose was consumed in significant
      amounts and phagocytosis of latex beads was enhanced, indicating that the
      monocytes had been activated. However, 1C6 did not enhance the production of
      monokines, TNF-alpha, and IL-1 alpha and -beta. The F(ab')2 fragment of 1C6 also
      activated monocytes, whereas 5B2 and the Fab fragment of 1C6 could not. To
      further examine monocyte activation, these cells were treated with
      phosphatidylinositol-specific phospholipase C. Increased glucose consumption and
      enhanced phagocytic activity by 1C6 were considerably reduced in monocytes
      treated with phosphatidylinositol-specific phospholipase C. In addition, we found
      that 1C6 stimulated the generation of inositol trisphosphate. These results
      demonstrate that the signal transmitted via the DAF molecule is capable of
      stimulating monocytes.

PMID- 1380539
TI  - Inhibition of HIV infection by a novel CD4 domain 2-specific monoclonal antibody.
      Dissecting the basis for its inhibitory effect on HIV-induced cell fusion.
AB  - HIV use the CD4 molecule as their primary cellular receptor. Residues in the N
      terminal domain (D1) of CD4 are crucial to HIV attachment through the gp120
      envelope component. However, other regions of CD4 appear to be required
      subsequently for virus- and cell-cell fusion. Little is understood of the post
      binding steps which may differ between HIV variants. We report a novel anti-CD4
      mAb that does not block CD4/gp120 binding, but that does efficiently block both
      viral infection and cell-cell syncytia formation, and define its contact site as
      residues in CD4 D2 using both mouse/human CD4 chimeras and CD4 substitution
      mutants. We also investigated the basis for its antiviral effect. Using the CD4
      D2 specific mAb, we identify another conserved step in HIV infection, as
      evidenced by its ability to neutralize a broad range of primary isolates and T
      cell-line passaged strains. Monovalent forms of the mAb were used to determine if
      its activity was due to masking of the D2 epitope, to steric inhibition, or
      bivalency. Our data indicate that both binding site and bivalency of the mAb
      underlie its potency. The need for bivalency is not simply explained by affinity,
      because monovalent forms can displace the intact mAb and reverse its protective
      effect. These results provide evidence that binding of the D2-specific mAb
      prevents structural alterations necessary for membrane fusion.

PMID- 1380540
TI  - Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus
      restricted tissue distribution indicates heterogeneity among human cytotoxic T
      lymphocyte-defined non-MHC antigens.
AB  - We determined the tissue distribution of 7 human minor histocompatibility (H) Ag.
      Each of these Ag is defined by one or more MHC class I-restricted CTL clones,
      previously generated from PBL primed against minor H Ag by HLA-identical bone
      marrow transplantation (BMT). CTL-mediated lysis of tissue-derived cells and
      cultured cell lines was used as an in vitro assay for minor H Ag expression of
      several human tissues. The Ag HA-3 (HLA-A1-restricted), HA-4 (HLA-A2 restricted),
      HA-6 and HA-7 (HLA-B7 restricted), and the male-specific Ag H-Y (HLA-A2 and B7
      restricted) were found to be expressed on cells of all tissues tested. In
      contrast, the HLA-A2-restricted Ag HA-1 and HA-2 were demonstrated on PHA-blasts,
      EBV-BLCL, purified T cells, B cells, monocytes, and immature thymocytes, but
      could not be demonstrated on skin-derived cultured fibroblasts, keratinocytes,
      melanocytes, cultured epithelial cells of kidney proximal tubili, and umbilical
      cord vein-derived endothelial cells. Incubation of the latter cell lines with
      rIFN-gamma, rTNF-alpha, and/or rIL-1 alpha, in concentrations shown to maximally
      increase their susceptibility to lysis by allo-MHC class I CTL, did not induce
      recognition by HA-1- and HA-2-specific CTL in vitro. These results indicate an
      ubiquitous tissue expression of the minor H Ag HA-3, -4, -6, -7 and H-Y in
      contrast to a to the hemopoietic cell lineage-restricted expression for HA-1 and
      HA-2. The heterogeneity in tissue expression of T cell-defined, class I
      restricted non-MHC Ag implies that they might be derived from intracellular
      proteins with either an ubiquitous or a more specialized cell type-specific
      function.

PMID- 1380541
TI  - Heteroclitic polyclonal and monoclonal anti-Gm(a) and anti-Gm(g) human rheumatoid
      factors react with epitopes induced in Gm(a-), Gm(g-) IgG by interaction with
      antigen or by nonspecific aggregation. A possible mechanism for the in vivo
      generation of rheumatoid factors.
AB  - Heteroclitic rheumatoid factors (RF) are specific for allotypic determinants,
      e.g., Gm(a) or Gm(g) on allogeneic, but not autologous IgG. All polyclonal RF we
      isolated from nine rheumatoid arthritis patients with circulating Gm(a-), (b+),
      (g-), (f+) IgG displayed dual heteroclitic activity for the Gm(a) and Gm(g)
      allotypes, as shown by using appropriate RBC agglutination assays and affinity
      columns bearing Gm(a+) or Gm(g+) IgG. To investigate possible mechanisms
      underlying the in vivo generation of heteroclitic RF, we tested the ability of
      nonspecifically and immune-specifically aggregated Gm(a-), (g-) IgG to function
      as targets for RF from Gm(a-), (g-) patients with rheumatoid arthritis. Heat
      aggregation (63 degrees C for 20 min) or binding to Ag (as in tetanus toxoid
      antitetanus toxoid complexes) induced a "functional" Gm(a+) and/or (g+) phenotype
      in Gm(a-), (g-) IgG from five healthy subjects and five rheumatoid patients, as
      suggested by the ability of these altered IgG to function as efficient targets
      for six heteroclitic RF in direct binding and competitive inhibition experiments.
      That heterocliticity and dual Gm(a), Gm(g) specificity can be features of a
      single antibody molecule was formally demonstrated by analysis of a monoclonal RF
      (IgM mAb 61) generated from a Gm(a-), (g-) rheumatoid patient. RF mAb 61
      displayed a high affinity (Kd, 10(-7) M) for IgG Fc fragment of Gm(a+) and (g+)
      IgG or aggregated autologous Gm(a-), (g-) IgG but did not bind to native
      autologous IgG. To investigate the molecular basis of the acquired Gm(a)
      phenotype, PBMC from five Gm(a-) patients with rheumatoid arthritis and two Gm(a
      ) normal subjects arthritis and two Gm(a-) normal subjects were cultured in vitro
      after activation with PWM. In most instances, these PBMC produced IgG that
      behaved as Gm(a+) in sensitive ELISA. Application of the polymerase chain
      reaction (PCR), using probes specific for the nucleotide sequence coding for the
      Gm(a) tetrapeptide, to the amplification of DNA from the in vitro-stimulated Gm(a
      ) normals or rheumatoid patients' PBMC provided no evidence for Gm(a) nucleotide
      sequences. The present data suggest that acquisition of the Gm(a) determinant by
      Gm(a-) IgG may result from subtle changes in the CH2-CH3 RF-binding region. Such
      changes would occur when Gm(a) IgG are complexed with Ag or nonspecifically
      altered, thereby providing a possible explanation for the induction of
      heteroclitic RF in Gm(a-) rheumatoid arthritis patients.

PMID- 1380542
TI  - Effect of phosphodiesterase inhibitors on bovine ciliary muscle and outflow
      facility.
AB  - To understand the aqueous outflow mechanism, we compared changes in the outflow
      facility with the response of ciliary muscle in fresh bovine eyes. The facility
      was measured in intact ocular globes. Theophylline, caffeine, and
      isobutylmethylxanthine (IBMX), all phosphodiesterase (PDE) inhibitors, increased
      outflow facility in a dose-dependent manner. However, neither epinephrine nor
      isoproterenol increased the outflow facility, regardless of their concentrations
      up to 10(-3) M. Neither epinephrine nor isoproterenol (0.01-1 microM)) relaxed
      the tone of bovine ciliary muscle, whereas theophylline and IBMX remarkably
      relaxed the muscle which had been contracted by carbachol, and also inhibited the
      nerve-mediated contraction. It is interesting that PDE inhibitors have a much
      greater influence on changes in outflow facility and ciliary muscle contraction
      than beta-adrenergic agonists.

PMID- 1380543
TI  - Pitfalls in the double labelling immunoelectron microscopy using one face of the
      grid.
AB  - We compared two procedures in the double labelling immunoelectron microscopic
      method of hormone-storing cells: one-faced and two-faced procedures. With the two
      faced procedure we got convincing results consistent with morphological finding,
      while we often got false results with the one-faced procedure. By the misleading
      one-faced procedure, the cell storing any one hormone will be misinterpreted as a
      multihormone storing cell. Therefore, it is concluded that the two-faced method
      is safer for the double labelling immunoelectron microscopic study.

PMID- 1380544
TI  - Temporal and spatial patterns of expression of laminin, chondroitin sulphate
      proteoglycan and HNK-1 immunoreactivity during regeneration in the goldfish optic
      nerve.
AB  - Current views suggest that the extracellular environment is critically important
      for successful axonal regeneration in the CNS. The goldfish optic nerve readily
      regenerates, indicating the presence of an environment that supports
      regeneration. An analysis of changes that occur during regeneration in this model
      may help identify those molecules that contribute to a favourable environment for
      axonal regrowth. We examined the distribution and expression of two extracellular
      matrix molecules, laminin and chondroitin sulphate proteoglycan, and a
      carbohydrate epitope shared by a family of adhesion molecules (HNK-1), using
      immunocytochemical detection in sections from the normal adult goldfish optic
      nerve and in nerves from one hour to five months following optic nerve crush. We
      also used in vitro preparations to determine if neurites in retinal explants
      could express these same molecules. The linear distributions of laminin and
      chondroitin sulphate proteoglycan immunoreactivity in control optic nerves are co
      extensive with the glia limitans, suggesting both are expressed by non-neuronal
      components surrounding the axon fascicles. Between one and three weeks
      postoperatively when axons elongate and reach their target, laminin and
      chondroitin sulphate proteoglycan immunoreactivity increases around the crush
      site and distally. At six weeks postoperatively the pattern of immunoreactivity
      has returned to normal. While the temporal pattern of changes in immunoreactivity
      is similar, the spatial pattern of these two extracellular proteins in the
      regenerating nerve differs. Chondroitin sulphate proteoglycan immunoreactivity is
      organized in discrete columns associated with regenerating axons while laminin
      immunoreactivity is more diffusely distributed. Examination of retinal explants
      reveals growing neurites express chondroitin sulphate proteoglycan but not
      laminin. Our results suggest that laminin is only associated with non-neuronal
      cells, while chondroitin sulphate proteoglycan is associated with axons as well
      as non-neuronal cells. HNK-1 immunoreactivity is co-extensive with both the glia
      limitans and axon fascicles and is more extensively distributed in the intact
      nerve than either laminin or chondroitin sulphate proteoglycan immunoreactivity.
      In contrast to laminin and chondroitin sulphate proteoglycan, HNK-1
      immunoreactivity is substantially decreased at the crush site within one week
      following optic nerve crush. HNK-1 immunoreactivity reappears through the crush
      site during the next several weeks, although non-immunoreactive regions, co
      extensive with areas predominantly containing non-neuronal cells, persist both
      proximal and distal to the crush, up to six weeks postoperatively. The pattern
      suggests that HNK-1 epitope expression by these non-neuronal cells is decreased
      during axonal regeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380545
TI  - Characterization of the sprouting response of axon-like processes from retinal
      ganglion cells after axotomy in adult hamsters: a model using intravitreal
      implantation of a peripheral nerve.
AB  - Peripheral nerves provide a favourable environment for damaged CNS axons to
      sprout and regenerate. It has also been demonstrated that retinal ganglion cells
      respond to a peripheral nerve segment grafted to the retina by emitting axon-like
      processes from the somatodendritic compartment into the graft. The factors
      influencing the pattern of sprouting of axotomized retinal ganglion cells were
      explored in this study by implanting a short segment of peripheral nerve, which
      did not come into contact with the retina, into the vitreous body of an eye whose
      optic nerve was concurrently crushed. Silver staining was used to assess the
      morphology of the retinal ganglion cells which underwent sprouting. Some retinal
      ganglion cells were induced to sprout axon-like processes; these emerged
      primarily from dendrites and less frequently from the soma or intraretinal axon.
      Implantation of a nonviable graft (freeze-thawed) elicited only minimal
      sprouting. These results suggest that diffusible factors secreted by cells in the
      graft are a possible stimulus to sprouting in axotomized retinal ganglion cells.
      Examination of the pattern of dendritic sprouting indicates that sprouting was
      most intense (in terms of number of sprouts per cell) at early times post
      axotomy. Moreover, a differential pattern of development of sprouts arising from
      individual primary dendrites of the same cell was observed; sprouts tend to arise
      from all primary dendrites initially but as the post-axotomy time increased,
      retraction of sprouts from some primary dendrites occurred. Concomitant with this
      retraction, however, there was an increase in the number of sprouts on those
      primary dendrites which were still in the active phase of sprouting. Selective
      stabilization of sprouts by extrinsic factors may account for this phenomenon.
      Changes in the area and outline (irregularity) of the somata of retinal ganglion
      cells with sprouts from two weeks to two months after optic nerve crush could be
      correlated temporally with the intensity of sprouting from the dendritic tree,
      suggesting that during sprouting, intrinsic mechanisms coordinate the responses
      of different cellular compartments. In contrast to extensive ectopic sprouting of
      axotomized retinal ganglion cells in the presence of an intravitreal graft, when
      a long peripheral nerve segment is grafted to the cut optic nerve, there is
      extensive axonal regeneration into the graft from retinal ganglion cells, most of
      which did not exhibit ectopic sprouting. Thus, a hierarchy of sprouting sites
      within a neuron seems to exist, with the damaged axonal tip being the most
      favoured site, followed by the dendrites, and then the intraretinal
      axon.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380546
TI  - Clearance of brain edema and macromolecules through the cortical extracellular
      space.
AB  - The transit routes of fluid and particulate matter through brain tissue remain
      unclear. The object of this study was to examine the movement of macromolecules
      through brain tissue to further clarify the clearance pathways of edema proteins
      as they migrate toward the cortex. For this purpose, albumin solution (20
      microliters rat albumin diluted to 65 mg/ml with mock cerebrospinal fluid (CSF))
      was intracerebrally infused into the caudate putamen, and the migration through
      brain tissue as well as through the ultrastructure of the cortical surfaces was
      explored using an immunocytochemical technique. The authors observed
      immunoreactive product on the glial limitans and pial lining as well as in the
      extracellular space of the cortical neuropil at 24 hours postinfusion, confirming
      that the protein had reached the cortical surface. To confirm the efflux of
      macromolecules into the subarachnoid CSF, 71,200 D fluorescein isothiocyanate
      dextran (FITC-dextran 71,200) was infused; cortical surfaces of brains removed en
      bloc as well as coronal sections were macroscopically observed under ultraviolet
      illumination at 15 minutes and 24 hours postinfusion. It was observed that
      infused FITC-dextran 71,200 mainly localized in the cortical white matter and
      caudate putamen of the infusion site at 15 minutes postinfusion and by 24 hours
      was distributed in the entire cortex of the infused hemisphere. However, the
      dynamics of lower-molecular-weight substances was completely different. The
      spatial distribution of FITC-dextran 4400 diverged upward toward the cortical
      surface and spread more extensively than FITC-dextran 71,200. These observations
      were consistent with a diffusion process as the spread of the tracer was
      dependent upon molecular size. These studies provide compelling evidence that a
      process other than bulk flow was involved in the spread of macromolecules through
      the extracellular space of the normal cortical neuropil to sink into the
      subarachnoid space. It was concluded that the CSF pathway via the extracellular
      space of the cortical neuropil is a primary route for clearance of extracellular
      edema proteins to the subarachnoid space and that diffusion is involved in this
      process.

PMID- 1380548
TI  - Effect of free gingival grafts on naturally-occurring recession in miniature
      swine.
AB  - Miniature swine exhibit naturally-occurring, progressive recession on facial
      surfaces of the permanent mandibular incisors. The purpose of this study was to
      determine whether placing a free gingival graft to augment the width of
      keratinized gingiva of mandibular incisors in miniature swine would prevent or
      retard recession at the grafted site compared to an untreated contralateral
      control site. In 8 litter-mate miniature swine, free gingival grafts were placed
      on the facial surface of the permanent central and lateral incisors on one side
      of the mandible. The contralateral mandibular incisors did not receive any
      treatment and served as controls. Clinical measurements, including eruption,
      recession, pocket depth, attachment level, and keratinized gingival width were
      obtained preoperatively, 2 to 3 weeks after surgery to assess the success of
      gingival augmentation, and 3, 6, and 9 months postoperatively. Eight grafted
      sites were successful and showed significant augmentation of the keratinized
      gingival width, with a mean increase of 5.8 +/- 0.7 mm, while 6 grafts failed and
      showed a slight decrease in the mean width of -0.4 +/- 0.5 from the preoperative
      to postoperative examination. All sites showed significant recession during the
      experimental period. Successful sites showed no statistically significant or
      clinically major difference in the rate or amount of recession than contralateral
      control sites. By 9 months, the average increase in recession from the baseline
      examination was 2.8 +/- 1.5 mm for successfully grafted sites and 2.6 +/- 1.3 mm
      for contralateral controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380547
TI  - Immunohistological localization of cell adhesion proteins and integrins in the
      periodontium.
AB  - The distribution of the cell adhesion proteins vitronectin, fibronectin,
      tenascin, and laminin as well as several integrin subunits, alpha 2, alpha 5, and
      alpha v, was studied in primate periodontal tissues. Full baboon mandibular
      sections were analyzed by immunohistochemical methods in order to localize the
      molecules studied in both soft and hard tissues. Vitronectin was associated with
      the connective tissue of the marginal gingiva, the periodontal ligament, as well
      as the endosteum and periosteum. A notable finding was the particularly high
      staining intensity of vitronectin in the periodontal ligament. Fibronectin was
      widely distributed in the periodontal connective tissue and was also localized to
      the pericellular matrix of osteocytes and blood vascular elements. Epithelial
      basement membranes stained positively for both fibronectin and tenascin. These
      proteins were also expressed in the periosteal and endosteal connective tissues
      and the periodontal ligament. The staining intensity for tenascin was higher in
      zones along the cementum and bone surfaces. Laminin was, characteristically,
      limited to basement membranes of epithelium and endothelium. The distribution of
      fibronectin, tenascin, and laminin is related to previous findings in other
      species. The localization of the several integrin alpha-subunits is also
      described in full baboon mandibular sections. The vitronectin receptor (alpha v)
      had a uniquely strong expression in osteoclasts of the alveolar bone and was
      found, at lesser intensity, on periodontal ligament fibroblasts. The fibronectin
      receptor alpha subunit, alpha 5, was also observed on osteoclasts, and, in
      addition, was widely distributed on fibroblasts, cementoblasts, and
      osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380549
TI  - Identification of luteinizing hormone-like proteins in the ovine pineal gland.
AB  - A chemical analysis was instigated to investigate the identity of the luteinizing
      hormone (LH)-like immunoactivity present in ovine pineal protein homogenates.
      Isolation of pineal LH-like material was accomplished using a 0.1 M ammonium
      sulphate (pH 4.0) extraction followed by anion-exchange chromatography. The
      resulting 3.0 M ammonium sulphate precipitate containing 70% of the LH-like
      immunoactivity was refractionated by cation-exchange and Sephadex G-100
      chromatography. Analysis of the pattern of recovered LH-like immunoactivity in
      the Sephadex G-100 eluate indicated the presence of molecular weight (MW) less
      than 60,000 besides MW 21,000 species of LH-like proteins. Bioactivity was tested
      in the rat Leydig cell steroidogenesis assay. In terms of steroid production, the
      activity was associated with the MW 21,000 LH-like proteins only. Further
      purification by CM-Sephadex chromatography and gel permeation HPLC was conducted
      in order to determine whether the physicochemical properties of pineal LH-like
      material represented endogenous LH, synthesized and released by the ovine
      pituitary. It is concluded by a variety of means, including polyacrylamide gel
      electrophoresis, and amino acid and carbohydrate analyses, that at least two
      molecular forms of immunoactive LH-like proteins occur in ovine pineal tissue.
      The MW 21,000 forms showed much similarity with ovine adenohypophyseal LH or with
      a complex mixture of its subunits. These observations contribute to the
      understanding of endocrine-endocrine transducing events that may occur in this
      organ.

PMID- 1380550
TI  - Serotonin content and melatonin production in the pineal gland of the male
      Djungarian hamster (Phodopus sungorus).
AB  - Diurnal variations in serum melatonin levels and pineal concentrations of
      serotonin (5-HT), N-acetylserotonin (NAS), 5-hydroxyindole acetic acid (5-HIAA),
      and melatonin were estimated in adult male Djungarian hamsters kept under long
      day (LD 16:8) or short-day (LD 8:16) photoperiods. The nocturnal increase in
      melatonin production was accompanied by a marked drop in pineal serotonin
      concentrations. Serotonin levels, however, decreased approximately 4 hr before
      pineal melatonin increased. Correlations of the mean values for pineal serotonin
      and pineal melatonin indicated significant correlations at both LD 16:8 (r = 
      0.92, P less than 0.001) and LD 8:16 (r = -0.85, P less than 0.001). The mean
      levels of pineal serotonin and serum melatonin were correlated as well (LD 16:8,
      r = -0.91, P less than 0.001; LD 8:16, r = -0.81, P less than 0.01). The levels
      of pineal serotonin declined at approximately the same time as serum melatonin
      levels increased. These data suggest that the drop in pineal serotonin is
      primarily a consequence of melatonin production (as reflected by increasing serum
      concentrations). Consequently, pineal concentrations of melatonin may not be the
      best estimate of actual melatonin production, but a measure of how much melatonin
      is accumulated within the pineal due to high synthesis rates while the release of
      the hormone from the gland is limited.

PMID- 1380552
TI  - Increase in susceptibility to EcoRII restriction of bacteriophage lambda produced
      by propagation on host cells growing in 5-azacytidine: a new in-vivo method for
      demonstration of DNA-methylation inhibition.
AB  - The efficiency of plating on EcoRII-restricting cells of bacteriophage lambda vir
      propagated on an Escherichia coli K-12 dcm+ host decreased with increase in
      concentration of 5-azacytidine (5-azaC) in the propagating medium. This
      illustrates, in-vivo, the inhibition of DNA-cytosine methylation induced by 5
      azaC and provides a simple system for the detection of DNA-methylation
      inhibitors.

PMID- 1380551
TI  - Evidence against substance P as a neurotransmitter at the neuroepithelial
      junction in rat colonic mucosa.
AB  - Substance P (SP) caused a concentration-dependent increase in short-circuit
      current of rat isolated colonic mucosal preparations (ED50 10 nM). The SP
      antagonist [D-Arg1,D-Pro2,D-Trp7,9, Leu11]SP (50 microM) did not increase short
      circuit current. Tetrodotoxin (3.1 microM) reduced the effect of a maximum
      concentration of SP (300 nM). This reduction was increased when tetrodotoxin was
      given with [D-Arg1,D-Pro2,D-Trp7,9,Leu11]SP. Increases in short-circuit current
      produced by electrical field stimulation were not reduced by [D-Arg1,D-Pro2,D
      Trp7,9,Leu11]SP. It is concluded that SP is not a transmitter at the
      neuroepithelial junction in rat colonic mucosa.

PMID- 1380553
TI  - Suppression of aflatoxin B1-induced lipid abnormalities and macromolecule-adduct
      formation by L-carnitine.
AB  - The fatty liver and hypolipidemia caused by aflatoxin B1 (AFB1) were studied in
      male Sprague-Dawley rats fed Purina Rat Chow with or without L-carnitine
      supplement for 6 weeks. In Experiment 1, the rats (n = 20) were divided into four
      groups, i.e., nonsupplemented control (NSC), nonsupplemented AFB1 (NSA),
      carnitine supplemented control (CSC), and carnitine supplemented AFB1 (CSA). The
      NSA and CSA groups were given an oral dose of [3H]AFB1 (1 mg/kg) 6 hr before
      kill. In Experiment 2 (n = 10) there were only NSA and CSA groups and they were
      killed 24 hr post-AFB1 administration. Hepatic and plasma concentrations of total
      lipid, triglycerides, AFB1-macromolecules adducts and urinary excretion of AFB1
      were determined. Carnitine supplementation ameliorated AFB1-induced hepatic
      steatosis and hypolipidemia. Supplementary carnitine reduced covalent binding of
      AFB1 to hepatic DNA, RNA, and protein. The carnitine effect was more pronounced
      after 24 hr than after 6 hr of AFB1 treatment. We conclude that supplementary
      carnitine suppressed AFB1-induced fatty liver and AFB1-macromolecule adduct
      formation in the rat.

PMID- 1380554
TI  - In vivo DNA/RNA adduction of 7,12-dimethylbenz(a)anthracene (DMBA) and
      benzo(a)pyrene (BaP) in the liver of rainbow trout (Oncorhynchus mykiss).
AB  - Juvenile rainbow trout were exposed via two intramuscular injections to either
      14C-DMBA for 24 hr or 14C-BaP for 48 hr, after which the livers were removed for
      DNA extraction and analysis. In the fish exposed to 14C-BaP, 0.2 ng was bound to
      the DNA, representing 0.5% of the total liver PAH-derived radioactivity and 2.38%
      of the administered dose. Liver DNA and RNA were found to contain 0.5% of the
      administered dose, respectively. Liver analysis of rainbow trout exposed to 14C
      DMBA demonstrated that 0.4 ng and 0.3 ng were bound to the DNA and RNA,
      respectively. This represents 1.0% and 0.6% of the liver DMBA burden,
      respectively. The DNA adduct concentrations formed were comparable to both in
      vitro and in vivo experiments with both mammals and fishes, indicating that
      relatively small, "environmentally realistic" doses of PAH have the ability to
      bind significantly to critical cellular macromolecules of young fish in vivo.

PMID- 1380555
TI  - Effect of two dentin bonding agents on microleakage in two different cavity
      designs.
AB  - Studies have shown that cavity design and dentinal bonding agents can affect
      composite resin microleakage. This study compared the microleakage at cementum
      dentin margins of box- and Vshaped preparations restored with two different
      bonding agents. Twenty freshly extracted, human third molars were prepared with
      one box-shaped and one V-shaped preparation on the mesial or distal surface.
      Occlusal margins were terminated in etched enamel and gingival margins were in
      cementum-dentin. There was no statistically significant difference (p greater
      than 0.05) between Dual Cure Scotchbond and Scotchbond 2 samples restored in the
      box-shaped preparations, but Scotchbond 2 had statistically significantly less
      microleakage (p less than 0.05) than Dual Cure adhesive in V-shaped preparations.
      The sealing of dentinal bonding agents varied in different cavity designs.

PMID- 1380556
TI  - Structural chromosome analysis by whole chromosome painting for assessment of
      radiation-induced genetic damage.

PMID- 1380557
TI  - Cholecystokinin-induced inhibition of endocytosis of receptor-bound substance P
      in pancreatic acinar cells.
AB  - Association of 125I-Bolton-Hunter labelled substance P (125I-BH-SP) to suspended
      pancreatic acinar cells of the guinea pig was studied. Cellular association at 37
      degrees C and 22 degrees C was inhibited by cholecystokinin octapeptide (CCK-8)
      in concentrations from 10(-9) to 10(-6)M, whereas another pancreatic
      secretagogue, carbachol, was uneffective. The CCK induced inhibition disappeared
      at low temperatures. CCK-8 mainly interfered with internalization of 125I-BH-SP
      into acinar cells. Increased extracellular Ca2+ and the Ca2+ ionophores A23187
      and ionomycin reduced association of 125I-BH-SP to cells whereas extracellular
      Ca2+ chelation with EGTA had the opposite effect. However, extra- and
      intracellular Ca2+ chelation did not affect the degree of CCK-induced reduction
      of 125I-BH-SP association to acinar cells but eliminated the effect of the
      calcium ionophore ionomycin. Three agents known to interfere with receptor
      recycling, namely monensin, methylamine and ammonium chloride reduced cell
      associated 125I-BH-SP. In a series of experiments, the cytoplasmic calcium
      concentrations ([Ca2+]i) during exposure to these three agents, to the CCK-8
      analogue caerulein and to ionomycin were determined. In all cases, [Ca2+]i was
      raised. The results indicate that endocytosis of receptor-bound 125I-BH-SP is
      regulated by CCK and that the endocytotic process is influenced by calcium.

PMID- 1380558
TI  - Prenatal biochemical screening.
AB  - Most fetal abnormalities occur in low-risk pregnancies. Screening techniques have
      been developed to help determine who in the low-risk group may actually be at
      high risk. Biochemical screening for chromosomal abnormalities and neutral tube
      defects have significantly increased their detection, but there is still
      considerable room for improvement.

PMID- 1380559
TI  - Prenatal differentiation of ventral abdominal wall defects. Are amniotic fluid
      markers useful adjuncts?
AB  - We retrospectively reviewed 29 cases of ventral abdominal wall defects to
      evaluate the usefulness of amniotic fluid markers in the prenatal assessment of
      those disorders. Amniotic fluid alpha-fetoprotein (AF-AFP) values were available
      in 17 cases diagnosed prior to 22 weeks' gestation and acetylcholinesterase (AF
      ACE) values, in 21 cases. All 7 fetuses with a gastroschisis had an elevated AF
      AFP, while only 2 of the 10 fetuses with an omphalocele had elevated values (P =
      .002). ACE was present in 80% of the cases of gastroschisis versus 27.3% of the
      cases of omphalocele (P = .03). With equivocal sonographic findings, a normal AF
      AFP and negative AF-ACE may be more compatible with an omphalocele.

PMID- 1380560
TI  - Studies on neurokinin antagonists. 2. Design and structure-activity relationships
      of novel tripeptide substance P antagonists, N alpha-[N alpha-(N alpha-acetyl-L
      threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-(phenylmethyl)-L-phenylalaninamide
      and its related compounds.
AB  - Continuing studies on the chemical modification of the previously reported novel
      tripeptide SP antagonist, N alpha-[N alpha-[N alpha- (tert
      butyloxycarbonyl)glutaminyl]-N1-formyl-D-tryptophyl]phenylalanine benzyl ester
      [Boc-Gln-D-Trp-(CHO)-Phe-OBzl (1)], are described herein. We initially
      investigated the stability of 1 in guinea pig plasma and liver homogenate to
      elucidate the most labile part in the structure. It was consequently revealed
      that the benzyl ester part was easily hydrolyzed to produce the inactive acid
      analog. Thus we searched for a benzyl ester surrogate that would be more
      resistant to hydrolytic enzymes. This approach found an isosteric amide
      structure, N-methyl-N-(phenylmethyl)amide, suitable in terms of potency and
      stability. Subsequent modification of the amino terminal into N alpha-acetyl-L
      threonine led to the most potent compound, N alpha-[N alpha-(N alpha-acetyl-L
      threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-(phenylmethyl)-L-phenylalaninamide
      [Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (5a, FR113680)]. This compound 5a potently blocked
      3H-SP binding to guinea pig lung membranes with IC50 of (5.8 +/- 0.78) x 10(-9)
      M. In vitro, 5a inhibited SP-induced contraction of isolated guinea pig trachea
      strips with IC50 of 2.3 x 10(-6) M and caused no contraction when used alone in
      this preparation up to 3.2 x 10(-5) M. In addition 5a exhibited no effect on the
      contraction induced by histamine or acetylcholine. Intriguingly, it was
      demonstrated in vivo that 5a suppressed the SP-induced bronchoconstriction and
      airway edema in guinea pigs with ED50 of 0.42 mg/kg and 0.66 mg/kg, respectively,
      when administered intravenously.

PMID- 1380561
TI  - 3'-Azido-3',5'-dideoxythymidine-5'-methylphosphonic acid diphosphate: synthesis
      and HIV-1 reverse transcriptase inhibition.
AB  - 3'-Azido-3'-deoxythymidine-5'-phosphonate was synthesized by a five-step reaction
      sequence. The 5'-phosphonate was inactive against HIV-1 in MT4 cells. The absence
      of activity against HIV-1 was at least partially explained by demonstrating that
      the Km value for the 5'-deoxy-5'-methylphosphonic acid diphosphate analog with
      HIV-1 reverse transcriptase (RT) was 320-fold greater than the Km value for 3'
      azido-3'- deoxythymidine-5'-triphosphate (AZTTP), and the kcat value for the 5'
      deoxy-5'-methylphosphonic acid diphosphate analog was one-seventh the value for
      AZTTP. These differences in kinetic constants were due to a change in the rate
      determining step from dissociation of the RT chain-terminated template-primer
      complex to the catalytic step. Thus, substitution of a methylene group for the 5'
      oxygen atom of AZTTP resulted in an 1800-fold reduction in the rate constant for
      RT-catalyzed phosphodiester bond formation.

PMID- 1380562
TI  - Mechanism of killer gene activation. Antisense RNA-dependent RNase III cleavage
      ensures rapid turn-over of the stable hok, srnB and pndA effector messenger RNAs.
AB  - The hok/sok, srnB and pnd systems of plasmids R1, F and R438 mediate plasmid
      maintenance by killing plasmid-free segregants. The systems encode exceptionally
      stable full-length mRNAs that code for potent cell toxins that kill the cells
      from within. The systems also produce truncated mRNAs whose appearance is
      correlated with killing activity. The truncated mRNAs are shortened by 35 to 70
      nucleotides in the 3' ends, but have the same 5' ends as the full-length
      transcripts. Translation of the stable killer mRNAs is regulated by unstable
      antisense RNAs that are complementary to the leader regions of the full-length
      and truncated mRNAs. We show here, that both the presence of the antisense RNA
      and of the host enzyme RNase III is required for rapid cleavage of the truncated
      mRNAs, and we map the cleavage point in the Hok mRNA in vitro and in vivo to be
      located between nucleotides +245 and +246. The RNase III cleavage products of the
      Hok mRNA were found to be very unstable in vivo. Thus, RNase III cleavage seems
      to be the initial event leading to decay of the killer mRNAs. In an rnc- strain,
      the truncated mRNA species were found in steady-state cells. This observation
      indicates that the truncated mRNAs are formed constitutively and independently of
      the presence of the antisense RNAs. Thus, the antisense RNAs prevent the
      accumulation of the truncated mRNAs solely by mediating their rapid hydrolysis by
      RNase III. Furthermore, the generation of the truncated killer mRNAs in the rnc-
      host indicate that RNase III is dispensable for induction of the killer gene
      systems. Based on these and on observations obtained previously, we present a
      molecular model that explains the activation of the killer mRNAs in plasmid-free
      segregants and after addition of rifampicin.

PMID- 1380563
TI  - High resolution functional analysis of antibody-antigen interactions.
AB  - A comprehensive mutational analysis was used to analyze the side-chains on human
      growth hormone (hGH) important for binding 21 different anti-hGH mouse monoclonal
      antibodies (MAbs) whose equivalent concentrations for 50% binding (EC50) ranged
      from approximately 10(7) to 3 x 10(10) M-1. A combination of homolog- and alanine
      scanning mutagenesis coupled with a robot-aided enzyme-linked immunosorbent assay
      were used to create high resolution "functional epitopes" for each MAb. Every
      functional epitope mapped to at least two polypeptide segments of hGH that were
      close together in the folded protein to form a patch. Although these patches
      sometimes overlapped, each was different indicating no two MAbs bound identically
      to hGH. The MAbs bound to determinants in loops and helices that were generally
      most accessible to a 9 A radius probe. Only a few side-chains dominated each
      functional epitope and these tended to be Arg greater than Pro greater than Glu
      approximately Asp approximately Phe approximately Ile (Ala, Cys and Trp were not
      tested). Our studies indicate that most of the accessible surface of hGH is
      potentially antigenic in the mouse and suggest that functional epitopes are
      dominated by fewer side-chains than may be in the contact epitope.

PMID- 1380564
TI  - Autism and developmental abnormalities in children with perinatal cocaine
      exposure.
AB  - Cocaine in all forms is the number one illicit drug of choice among pregnant
      women. Records of 70 children with cocaine exposure in utero who were referred
      for developmental evaluation at a large inner-city hospital were reviewed in an
      effort to determine whether a specific pattern of abnormalities could be
      discerned. Patients received physical examinations, neurological screenings, and
      behavioral and developmental assessments based on the Gesell Developmental
      Inventory, and the Denver Developmental Screening Test. Documentation of
      specified drug use was obtained by history. Mean age (SEM) at referral was 19.2
      (1.7) months. All mothers used cocaine in one of its forms, although polydrug use
      was common. Growth parameters were low (median = 15th percentile). Significant
      neurodevelopmental abnormalities were observed, including language delay in 94%
      of the children and an extremely high frequency of autism (11.4%). The high rate
      of autistic disorders not known to occur in children exposed to alcohol or
      opiates alone suggests specific cocaine effects.

PMID- 1380565
TI  - Mesenteric microcirculatory changes in nonlethal hemorrhagic shock: the role of
      resuscitation with balanced electrolyte or hypertonic saline/dextran.
AB  - Class I and II hemorrhage has been routinely treated clinically with 2-2.5 times
      the volume of shed blood as balanced electrolyte solution. Although this regimen
      has been shown to adequately restore arterial pressure in trauma patients, it is
      not clear that it uniformly restores regional perfusion. Since it is becoming
      apparent that the gut plays a major role in the development of the posttraumatic
      septic state, we studied the effects of graded doses of balanced electrolyte
      resuscitation on the mesenteric microcirculation. Regimens consisting of one (1 x
      LR), two (2 x LR), or three (3 x LR) times the volume of shed blood as lactated
      Ringer's (LR) solution or 7.5% hypertonic saline and 6% dextran (HSD) equal to
      one seventh the volume of shed blood were given to groups of anesthetized
      (urethane-chloralose) male Sprague-Dawley rats after 30 minutes of hemorrhage to
      50% of baseline mean arterial blood pressure. The microcirculation of the distal
      ileum was observed using an in vivo video microscope. Mean arterial pressure and
      ileal A1 diameters returned to baseline values with HSD within 20 minutes
      following this moderate hemorrhage. Additionally, A1 diameters returned to
      baseline in the 2 x LR and 3 x LR groups. A1 vessels remained significantly
      constricted in the 1 x LR group. Mean arterial pressure remained significantly
      lower than the baseline value in all of the LR groups. We conclude that in this
      model, HSD is superior to LR for restoration of blood pressure. In restoring A1
      diameters, LR is equivalent to HSD only when volumes of balanced electrolyte two
      and three times shed blood volume are given.

PMID- 1380566
TI  - Clinical and haematological diversity of sickle cell disease in Saudi children.
AB  - Sickle cell disease (SCD) exhibits itself in a broad spectrum of clinical
      behaviour ranging from a mild disease to an incapacitating condition. In this
      study, we have attempted to investigate the clinical diversity of SCD in
      different regions of Saudi Arabia. The results of haematological parameters and
      clinical manifestations in 41 children with SCD from the eastern province where
      the disease is mild, were compared with results obtained in 51 children from the
      south-western province (SWP), where the disease has been shown to be more severe.
      The severity index (SI) of patients from the eastern province ranged from 2 to 11
      with a mean of 4.5 and in patients from the south-western province, the SI ranged
      from 2 to 18 with a mean of 9.5. In addition, the occurrence of hand and foot
      syndrome, vaso-occlusive crisis, and increased frequency of requirement of blood
      transfusion and hospitalization differentiated the clinical presentation of SCD
      in the patients from south-western province from those in the eastern province.
      Red blood cell level, total haemoglobin and packed cell volume were lower in the
      SCD children from the south-western province. Haemoglobin A2 level was
      significantly higher, while haemoglobin F, packed cell volume (PCV), mean
      corpuscular volume (MCV), and mean corpuscular haemoglobin concentration (MCHC)
      did not show any significant differences. HbF level did not influence the
      haematological parameters significantly in the SWP patients. It is concluded that
      the SCD in Saudi population is heterogeneous clinically and haematologically.

PMID- 1380567
TI  - Therapies for benign prostatic hyperplasia.

PMID- 1380568
TI  - Therapies for benign prostatic hyperplasia.

PMID- 1380569
TI  - [Enrichment of stem cells--with special reference to the analysis of CD34
      positive cells].

PMID- 1380570
TI  - [IgM HCV antibody in chronic hepatitis and liver cirrhosis].
AB  - To evaluate the role of IgM specific antibody in the diagnosis and monitoring of
      the patients with chronic hepatitis C, sera from 114 cases with chronic hepatitis
      C and liver cirrhosis were tested. IgM antibody to hepatitis C virus was detected
      in 40.0% of CAH, as compared with 21.4% of CIH, 17.4% of LC, 20.0% of LC with
      HCC. IgM antibody was also detectable in cases with high level of s-ALT. Patients
      with positive this antibody have high titer of IgG antibody to hepatitis C virus.
      In summary, testing for this antibody may be useful to evaluate the recurrence or
      disease activity and may also be helpful in IFN therapy.

PMID- 1380571
TI  - [Clinical studies of recombinant human granulocyte colony-stimulating factor in
      elderly patients with malignant lymphoma].
AB  - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given in
      combination with chemotherapy in elderly patients (greater than or equal to 65
      years old) with malignant lymphoma, and the therapeutic efficacy and the
      incidence of side effects were determined. The subjects consisted of 5 males and
      8 females with a median age of 74 years. One patient had Hodgkin's disease and 12
      had non-Hodgkin's lymphoma. Regarding lymphoma stage, 2 were in stage II, 3 were
      in stage III, and 8 were in stage IV. The chemotherapy used was COP-BLAM in 8
      patients, COP-BLAM III in 2, IMV-triple P in 2, and ACVP-16 in 1. Treatment with
      rhG-CSF (1.5 micrograms/kg/day) was commenced during or after the 2nd course of
      chemotherapy when the neutrophil count dropped to greater than or equal to
      1,000/microliters, and was continued until the recovery of either the neutrophil
      or leukocyte count to 10,000/microliters or 20,000/microliters, respectively. The
      neutrophil nadir in the non-G-CSF group was 367.3 +/- 231.6/microliters. In the G
      CSF group it was 754.6 +/- 116.4/microliters for the second course, with the
      difference between the 2 groups being significant (p less than or equal to 0.05).
      Also, the following time periods were significantly shorter in the G-CSF group
      than the non-G-CSF group: 1) the duration of a neutrophil count less than
      1,000/microliters, 2) the duration of fever (greater than or equal to 37.5
      degrees C), and 3) the time to recovery from the neutrophil nadir.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380573
TI  - Ion channels and control of contractile activity in urinary bladder smooth
      muscle.

PMID- 1380572
TI  - Ionic mechanisms involved in muscarinic regulation of neuronal and paraneuronal
      activity.
AB  - The characteristics of neuronal and paraneuronal muscarinic inhibition and
      excitation were analyzed using rat caudate nucleus (CN) slices and isolated
      chromaffin cells obtained from the rat adrenal medulla. In CN neurons, either
      acetylcholine (ACh), carbachol, or muscarine inhibited orthodromically activated
      firing, while nicotine had no effect on neuronal activity. Muscarine decreased
      the amplitude of EPSPs without altering the resting membrane potential (RMP),
      input impedance and EPSP time courses. These results indicate that muscarinic
      receptors produce the presynaptic inhibition of synaptic transmission in the CN.
      In adrenal chromaffin cells, it was found that ACh, muscarine, and nicotine all
      increased extracellularly recorded firing. During voltage clamp recording at the
      RMP, ACh induced a transient inward current (fast response) followed by a long
      lasting current (slow response). Muscarine induced the slow response, whereas
      nicotine induced the fast response. Muscarine reduced the inward K+ current
      produced by the application of a high K+ medium to cells. During patch clamp
      recording, muscarine decreased the opening rate of the single K+ channels. These
      results indicate that the muscarinic excitation of adrenal chromaffin cells was
      triggered by a reduction in the number of active K+ channels at the RMP.

PMID- 1380574
TI  - Inducible nitric oxide synthase and vascular smooth muscle.

PMID- 1380575
TI  - Formation of muscle-derived nitric oxide (MDNO) is mediated by an inducible
      nitric oxide synthase.

PMID- 1380576
TI  - Depolarization-activated chloride current inhibitable by isoprenaline and 8-Br
      cAMP in endothelial cells.

PMID- 1380577
TI  - Stabilized recording of ACh activated non-selective cationic conductance in
      guinea-pig ileal smooth muscle using a nystatin-permeabilized whole-cell
      recording.

PMID- 1380578
TI  - Excitatory effect of substance P on the antral circular muscle of the guinea-pig
      stomach.

PMID- 1380579
TI  - Propagation of electrical and mechanical activity in uterine smooth muscle: a
      functional role for stretch-sensitive channels.

PMID- 1380580
TI  - Increased function of Ca(2+)-activated K+ channels in the resting state of
      carotid arteries from spontaneously hypertensive rats.

PMID- 1380581
TI  - Effects of potassium channel blockers on the spontaneous electrical and
      mechanical activities of circular smooth muscles of the guinea-pig stomach.

PMID- 1380582
TI  - Potentiation of muscarinic inward current by calcium released from internal
      stores.

PMID- 1380583
TI  - Mechanisms for glucocorticoid inhibition of immediate hypersensitivity reactions
      in rats.
AB  - The inhibitory mechanisms of immediate hypersensitivity reactions by
      glucocorticoid (GC) were studied in rats. Homologous passive cutaneous
      anaphylaxis (PCA) mediated by IgE antibodies and cutaneous reactions caused by
      histamine, serotonin and leukotriene C4 were elicited at the same time in the
      same rats. Three kinds of GC, hydrocortisone, prednisolone and dexamethasone,
      inhibited all these reactions significantly. Although mediator-induced cutaneous
      reactions were inhibited transiently around 2 hours after GC administration,
      inhibition of PCA was more potent and lasted longer. A time lag seemed to be
      essential for both inhibitions. IgE antibody-mediated histamine release in vivo
      in the rat peritoneal cavity was also inhibited by GC administration
      significantly, and the inhibition was long lasting when compared to those of the
      mediator-induced cutaneous reactions. Tyrosine amino-transferase (TAT) activity
      in the rat liver increased significantly by GC administration, and the increased
      TAT activity was completely abrogated by simultaneous administration of 5 mg/kg
      of cycloheximide (CH). In the same experimental condition, although inhibition of
      histamine-induced cutaneous reaction by GC was completely abrogated, the
      inhibition of PCA elicited at the same time in the same rats was only partially
      attenuated. Furthermore, the same dose of CH little affected the dexamethasone
      inhibition of histamine release in the rat peritoneal cavity, although the
      increase of TAT activity in the liver of the same rats was completely abrogated.
      These results demonstrate that PCA is inhibited by GC through at least 2
      mechanisms, inhibition of mediator release from mast cells and non-specific
      inhibition of vascular permeability increase caused by released mediators.
      Although the latter action of GC is dependent upon protein synthesis, the former
      seems to be mediated by a unique mechanism independent of protein synthesis.

PMID- 1380584
TI  - [Immediate results of surgical treatment of gastric cancer complicated by
      anemia].
AB  - The immediate results of surgical treatment of gastric cancer complicated by
      anemia in 137 patients are presented. Resectability rate was 66.4%, total
      postoperative lethality--4.4%, incidence of postoperative complications--21.9%.
      In the process of preoperative preparation, correction of anemia was performed in
      35% of the patients. At the postoperative period, severity degree of anemia had
      no influence on the incidence of postoperative complications provided that the
      reliable methods for creation of esophago-intestinal and gastrointestinal
      anastomoses were used.

PMID- 1380585
TI  - [Use of the fluorescent analysis in early diagnosis of cancer of the stomach].
AB  - The effectiveness of a fluorescent analysis in the diagnosis of gastric cancer
      was studied in 280 patients. Fluorescence of a tumor was noted in 87% of cases.
      Dependence of fluorescence of a tumor on its sizes was revealed: in tumor
      diameter less than 1 cm, fluorescence was revealed in 94% of cases, more than 4
      cm--in 76%. In infiltrative growth, only 74% of tumors were fluorescent. To
      define the possibility of the use of a fluorescent analysis in the differential
      diagnosis of gastric diseases, 490 patients with presumptive diagnosis of chronic
      gastritis, gastric ulcer disease, polyposis were examined. In diagnosis of
      +malignant polyps in 91.5% of cases, results of the fluorescent analysis
      concurred with the findings of histologic study. Probability of establishing the
      correct diagnosis by the data of fluorescent analysis in ulcer disease is equal
      to 87.5%, in chronic gastritis--86%.

PMID- 1380586
TI  - [Several components of plasma hemostasis in patients with suppurative processes
      in the abdominal cavity].
AB  - Blood and urine concentrations of antithrombin-III, plasminogen, alpha 2
      macroglobulin, alpha 1-antitrypsin, degradation products of fibrinogen-fibrin
      were studied in patients with abdominal suppuration. Noticeable deviations from
      the normal values especially marked in the severe process indicated the
      development of DIC syndrome and renal failure. Heavy combined treatment promoted
      normalization of the hemostasis shifts and eliminated pyo-inflammatory processes
      in the abdominal cavity.

PMID- 1380587
TI  - Amiodarone decreases cardiac beta-adrenoceptors through an antagonistic effect on
      3,5,3' triiodothyronine.
AB  - Because surprising similarities exist between the cardiac effects of amiodarone
      and those observed during hypothyroidism, we tested three different mechanisms of
      action in rats to determine whether amiodarone might act by inducing a tissular
      hypothyroidism: (a) a decrease in thyroid secretion, (b) an inhibiting effect on
      the conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3), and (c) a
      direct antagonistic effect on the cellular action of T3. Five groups of rats,
      treated orally for 7 or 13 days, were studied: I, control (0.5 ml saline for 7 or
      13 days, n = 14); II, amiodarone (50 mg/kg for 7 days, n = 5); III, iopanoic acid
      (100 mg/kg for 13 days, n = 7); IV, control + T3 (0.5 ml saline for 13 days and
      0.5 mg/kg T3 for the last 6 days, n = 5); V, amiodarone + T3 (amiodarone 50 mg/kg
      for 13 days and 0.5 mg/kg T3 for the last 6 days, n = 5). Cardiac beta
      adrenoceptor density (CBARD) and heart rate (HR) were the two endpoint parameters
      investigated. Thyroid status was evaluated by serum thyrotropin (TSH), T4, T3,
      rT3 concentrations and liver type I 5'-deiodinase (5'D-I) activity. Amiodarone
      (group II) decreased CBARD (-22%, p less than 0.05) without altering thyroid
      secretion and T3 serum level, whereas 5'D-I was strongly inhibited (-90%, p less
      than 0.01). Iopanoic acid had no effect on CBARD and HR, but deeply inhibited 5'D
      I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380588
TI  - Combination of nifedipine and doxazosin in essential hypertension.
AB  - Pharmacodynamic and pharmacokinetic interactions have been reported when an alpha
      1-antagonist is combined with a calcium antagonist. We evaluated the clinical
      usefulness of the combination of nifedipine (20 mg twice daily, b.i.d.) and
      doxazosin (2 mg once daily, o.d.) in hypertensive patients in whom blood pressure
      (BP) control was suboptimal after doxazosin (group A) or nifedipine (group B) as
      monotherapy and investigated the underlying kinetic and dynamic interactions,
      including changes in vascular responsiveness to i.v. infusions of angiotensin II
      (ANGII) and phenylephrine (PE). The combination was well tolerated and associated
      with further significant reductions in BP. After 4 weeks of combined therapy,
      average supine BP over 8 h was 122/77 in group A and 137/80 in group B as
      compared with 140/86 and 150/88 mm Hg, respectively, during monotherapy +
      placebo. The combination attenuated both phenylephrine and ANG-induced pressor
      responses: e.g., the mean PD15 values (dose of agonist required to increase
      systolic BP by 15 mm Hg) for group A at 1.5-3 h were 3.5 micrograms/kg/min for PE
      and 7.5 ng/kg/min for ANGII as compared with 2.9 and 2.3, respectively, during
      treatment with doxazosin and placebo. There was no evidence of a significant
      kinetic interaction between the two drugs and, in particular, addition of
      nifedipine had no effect on the steady-state kinetics of doxazosin. In
      conclusion, doxazosin and nifedipine are an effective antihypertensive
      combination in patients who require treatment with more than one drug.

PMID- 1380589
TI  - Sotalol exhibits reverse use-dependent action on monophasic action potentials in
      normal but not in infarcted canine ventricular myocardium.
AB  - In 12 anesthetized mongrel dogs (30 mg/kg pentobarbital), a thoracotomy was
      performed, and the left anterior descending coronary artery was ligated
      proximally. Eight to 12 days later, monophasic action potentials were recorded
      endocardially from the apex of the noninfarcted right ventricle and infarcted
      areas of the left ventricle, and the effects of 1.5 mg/kg intravenous sotalol
      were evaluated. Monophasic action potentials from the infarcted zone of the left
      ventricle were obtained from areas where fractionated bipolar electrograms could
      be recorded; this was histologically confirmed. After sotalol, in sinus rhythm,
      the monophasic action potential duration at 90% repolarization of the infarcted
      zone increased from 186 +/- 31 to 226 +/- 45 ms (+ 22%, p less than 0.05), and
      monophasic action potential duration of the noninfarcted zone increased from 184
      +/- 31 to 225 +/- 47 ms (+ 22%, p less than 0.05). Programmed ventricular
      stimulation was performed with single extrastimuli at a basic drive cycle length
      of 300 ms. With long coupling intervals (290 ms), monophasic action potential
      duration of the infarcted zone increased from 165 +/- 23 to 183 +/- 25 ms (+ 11%,
      p less than 0.05) after sotalol; and monophasic action potential duration of the
      noninfarcted zone increased from 159 +/- 20 to 180 +/- 25 ms (+ 13%, p less than
      0.05). With short coupling intervals (200 ms), the monophasic action potential
      duration of the noninfarcted zone increased from 157 +/- 19 to 173 +/- 18 ms (+
      10%, p less than 0.05), and monophasic action potential duration of the
      noninfarcted zone increased from 150 +/- 18 to 157 +/- 18 ms (+ 5%, NS).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380590
TI  - d-Sotalol has opposite effects from encainide and propafenone on the proportion
      of episodes of ventricular tachycardia that are sustained in an experimental
      substrate for reentry.
AB  - Conversion of sustained ventricular tachycardia (VT) to nonsustained VT may be a
      potent mode of antiarrhythmic drug action, whereas a drug's conversion of
      nonsustained VT to sustained VT could produce serious clinical complications. We
      tested the effects of two class Ic drugs [encainide (1, 2, and 4 microM) and
      propafenone (0.1, 0.3, and 0.6 microM)) and a class III drug (d-sotalol (25, 50,
      and 100 microM)] on the proportion of VT episodes that were sustained (duration
      greater than 1 min) in an acute in vitro model of reentrant VT in left
      ventricular (LV) epicardium: a Langendorff-perfused rabbit heart whose LV
      endocardial and midwall cells have been killed by a selective freezing procedure.
      Multiple VT episodes were generated by increasing the stimulation rate until self
      sustained activity occurred. Some episodes spontaneously terminated in less than
      1 min; others lasted longer and were terminated by transient cooling of the
      heart. Both encainide and propafenone increased the fraction of episodes of
      sustained VT in all preparations; the increase was significant in 4 of the 5
      encainide preparations (p less than 0.02) and 4 of the 5 propafenone preparations
      (p less than 0.003). d-Sotalol, on the other hand, decreased the fraction of
      sustained VT in all preparations; the decrease was significant (p less than
      0.002) in 4 of the 5 preparations. All 3 drugs increased the basic cycle length
      of pacing at which VT was induced and the cycle time of the resulting VT. These
      results of this new assay of drug action may be related to the drugs' different
      mechanisms of prolonging refractoriness.

PMID- 1380591
TI  - Effects of isradipine on plasma renin activity in sodium-loaded and -depleted
      conscious rabbits.
AB  - The antihypertensive effect of calcium antagonists is altered little by high salt
      intake or concomitant diuretic treatment. We therefore investigated whether
      modest changes in the salt balance might alter the acute response of the renin
      angiotensin system to the calcium antagonist isradipine in conscious rabbits.
      Mongrel rabbits with indwelling arterial and venous catheters were pretreated
      with either a single subcutaneous injection of 20 mg/kg furosemide 24 h before
      the experiment [sodium depletion (SD)] or the addition of 0.45% NaCl to the
      drinking water, which was available ad libitum for 24 h [sodium loading (SL)].
      Compared with SL, SD pretreatment modestly increased plasma renin activity and
      lowered body weight; mean arterial pressure and heart rate were unchanged.
      Isradipine (10, 30, and 100 micrograms/kg) infused into the femoral vein catheter
      decreased blood pressure and increased heart rate similarly in both groups.
      Increases in plasma renin activity plotted as a function of the decreases in
      blood pressure showed a significantly steeper slope in SD than in SL animals.
      When blood pressure started to recover 15 min after the end of drug infusion,
      plasma renin activity decreased in SL animals only. Therefore, SL or SD strongly
      influences the responsiveness of the renin-angiotensin system to calcium
      antagonists, and this may be one reason why high salt intake does not diminish
      the antihypertensive effect of calcium antagonists and a calcium
      antagonist/diuretic combination may not yield optimal therapeutic results.

PMID- 1380592
TI  - Stimulation by retinoids of tissue-type plasminogen activator secretion in
      cultured human endothelial cells: relations of structure to effect.
AB  - Retinoic acid induces tissue-type plasminogen activator (t-PA) but not
      plasminogen activator inhibitor-1 (PAI-1) expression in cultured human umbilical
      vein endothelial cells (HUVEC). To further investigate the relation between the
      structure of the retinoids and their ability to induce t-PA synthesis in vitro,
      11 analogues were studied in HUVEC culture. The retinoid analogues were
      classified into one of three groups according to their t-PA-inducing potential.
      Group 1 showed little induction (0.9- to 1.9-fold after 48 h) at concentrations
      between 10(-8) and 10(-6) M. Group 2, which includes all-trans-retinoic acid,
      induced t-PA threefold to fivefold at 10(-6) M but had little effect at 10(-8) M
      (less than threefold). Group 3, which comprises arotinoid acid (RO-13-7410) and
      RO-13-6307, induced t-PA antigen secretion fivefold at 10(-8) M. The retinoids of
      groups 2 and 3 had a terminal carboxyl group and alkyl substitution of the
      lipophylic head of the retinoid skeleton. The group 3 retinoids also contained an
      aromatic ring. The t-PA-inducing activity of these third-generation retinoids
      correlates to some extent with other activities, including regression of
      papilloma, keratinization in vivo, and clonal inhibition of tumor cell lines in
      vitro. Some of the retinoids caused a small but significant (up to 1.5-fold at 24
      h) increase in PAI-1 antigen secretion. The group 3 retinoids appear to be
      sufficiently potent inducers of t-PA secretion to warrant further investigation
      in in vivo animal models.

PMID- 1380594
TI  - Isoproterenol impairs the rat coronary vasculature: effects of angiotensin
      converting enzyme inhibition.
AB  - The purpose of the present study was to evaluate whether in addition to its
      myocardial effects, chronic beta-adrenergic stimulation with isoproterenol could
      modify the coronary vasculature. For this purpose, rats were treated for 2 weeks
      with isoproterenol, and the hearts were isolated for determination of the minimal
      coronary vascular resistance under maximal vasodilation and then perfused-fixed
      for morphometry of the coronary arteries. In addition, because isoproterenol
      stimulates the renin-angiotensin system (RAS), the effects of angiotensin
      converting enzyme (ACE) inhibition on the coronary vasculature were assessed.
      Isoproterenol increased heart weight by 65% and minimal coronary resistance by
      55%. This effect was associated with medial thickening in intermediate (32%) and
      large coronary arterioles (26%). Cilazapril, a long-acting ACE inhibitor,
      completely prevented the medial thickening induced by isoproterenol and
      normalized the minimal coronary resistance. We conclude that impairment of the
      rat coronary vasculature induced by chronic beta-adrenergic stimulation might be
      in part mediated by activation of the RAS.

PMID- 1380593
TI  - A comparison of the characteristics of angiotensin receptors in the renal and
      mesenteric vascular beds of the anesthetized cat.
AB  - Experiments were performed in anesthetized cats to compare the characteristics of
      angiotensin receptors in the renal and mesenteric vascular beds. Injection of
      either angiotensin II (Ang II; 0.3-30 ng) or angiotensin III (Ang III; 0.3-30 ng)
      directly into the superior mesenteric or renal artery caused dose-related,
      reproducible reductions in mesenteric and renal blood flow, respectively. Ang II
      and Ang III were equipotent as vasoconstrictors in both vascular beds. The
      peptide angiotensin receptor antagonists saralasin and Ile7-Ang III (1
      microgram/kg/min intravenously, i.v.) and the nonpeptide angiotensin receptor
      antagonist DuP 753 (3 mg/kg plus 20 micrograms/kg/min i.v.) caused a rightward
      displacement of dose-response curves to Ang II or Ang III in both the mesenteric
      and renal vasculature. Vasoconstrictor responses to Ang II or Ang III in either
      vascular bed were blocked to similar extents by each antagonist. In separate
      cats, the dose of the antagonists required to cause a 10-fold rightward
      displacement of the Ang II dose-response curve (DR10) in both vascular beds was
      determined. The DR10 values indicated that the potency of each antagonist was
      similar in the renal and mesenteric vascular beds. These results provide no
      evidence to suggest that angiotensin receptors mediating vasoconstriction in the
      renal and mesenteric vasculature have different characteristics.

PMID- 1380595
TI  - Characterization of membrane-bound cyclic nucleotide phosphodiesterases from
      bovine aortic smooth muscle.
AB  - This study reports the isolation and characterization of cyclic nucleotide
      phosphodiesterases (PDEs) associated with membrane fraction in comparison to
      cytosolic forms from bovine aorta. DEAE-Sephacel chromatography of a solubilized
      membrane fraction from a homogenate, prepared under isotonic conditions in the
      presence of protease inhibitors, yielded one major peak of PDE activity that
      specifically hydrolyzed cAMP and was not stimulated by calmodulin: It appeared to
      contain two subtypes of PDE. The first subtype belonged to the cyclic GMP (cGMP)
      inhibited PDE family, (PDE III): It had an apparent Km value of 0.4 microM and
      was potently inhibited by cGMP, LY186126, and cilostamide. The second was a
      rolipram-sensitive PDE form (PDE IV) that had an apparent Km value for cAMP
      hydrolysis of 1.1 microM, was selectively inhibited by rolipram and denbufylline,
      and was insensitive to cGMP. These two forms had kinetic and pharmacologic
      profiles similar to those resolved by DEAE-Sephacel from the cytosolic fraction
      (105,000 g supernatant). In addition, DEAE-Sephacel chromatography of the
      cytosolic fraction revealed another peak of PDE activity that could be resolved
      with high-performance liquid chromatography (HPLC) into a calmodulin-sensitive
      form that preferentially hydrolyzed cGMP (PDE I) and a calmodulin-insensitive
      form that specifically hydrolyzed cGMP (PDE V). The presence of a PDE III in
      vascular smooth muscle that exhibited similarities to the cGMP-inhibited PDE from
      cardiac tissues, the target of several new cardiotonic agents, suggests that a
      single mechanism of action may account for the cardiotonic and vasodilating
      properties of PDE III inhibitors.

PMID- 1380596
TI  - In vivo effects of amiodarone on cardiac beta-adrenoceptor density and heart rate
      require thyroid hormones.
AB  - To assess if the anti-beta-adrenergic effect and the bradycardia induced by
      amiodarone were mediated by thyroid hormone, we investigated these effects of
      amiodarone in euthyroid and hypothyroid rats. We studied control rats,
      thyroidectomized rats, control rats treated with amiodarone (50 mg/kg for 8
      days), and thyroidectomized rats treated with amiodarone. At the end of the
      treatment, free thyroid hormone levels (FT4 and FT3) were determined, and cardiac
      beta-receptor density (Bmax) and affinity (Kd) were assayed by using (-)
      [125I]iodocyanopindolol as radioligand. Resting heart rate (rHR) was also
      assessed every day in control and thyroidectomized rats, before and after
      amiodarone. In hypothyroid rats, in which free thyroxine (FT4) was not detectable
      and free 3,5,3'-triiodothyronine (FT3) was only 16% that of euthyroid rats, Bmax
      (14.1 +/- 2.5 fmol/mg, n = 7) and rHR (259 +/- 9.7 beats/min, n = 6) were
      significantly lowered compared with euthyroid rats (Bmax:18.4 +/- 3.4 fmol/mg, n
      = 7; rHR:277 +/- 4.1 beats/min, n = 5). Amiodarone treatment decreased Bmax (13.6
      +/- 2.9 fmol/mg, n = 8) and rHR (252 +/- 5.5 beats/min, n = 5) only in euthyroid
      rats and did not produce significant cardiac effects in hypothyroid rats. (Values
      are given as mean +/- SD.) We conclude that a minimum serum thyroid hormone
      concentration is a necessary condition for amiodarone to produce some of its
      cardiac effects. An antagonistic reaction to thyroid hormones at the cellular
      level can be postulated as a mechanism of the cardiac anti-beta-adrenergic action
      of amiodarone.

PMID- 1380597
TI  - Inotropic effects of calcium antagonists in the cardiomyopathic Syrian hamster.
AB  - The inotropic responses of papillary muscles isolated from the BIO 14.6
      cardiomyopathic Syrian hamster were compared with those of age-matched F1B
      controls. Length-tension curves revealed the preservation of contractile function
      at 1-2 months of age and significant loss of function at 4-6 months of age.
      Papillary muscles prepared from 4-6-month-old myopathic hamsters were
      significantly less sensitive to increasing frequency of stimulation than were
      controls (p less than 0.05). There were no differences in the responses to
      nifedipine, Bay K 8644, diltiazem, or gallopamil. Only verapamil demonstrated a
      biphasic inotropic response in the cardiomyopathic hamster with a low-dose
      positive inotropic effect (131 +/- 4% at 4 +/- 2 x 10(-7) M) and a 50-fold higher
      IC50 for negative inotropy compared with F1B controls (200 +/- 30 vs. 4.0 +/- 1.0
      microM). Verapamil is also a less potent negative inotrope in 1-2-month-old
      myopathic papillary muscles compared with controls (IC50, 280 +/- 70 vs. 32 +/-
      10 microM; p less than 0.05). These inotropic effects are not shared by the other
      calcium channel modulators studied (i.e., nifedipine, Bay K 8644, diltiazem,
      gallopamil). These findings do not support the presence of a functional defect in
      the sarcolemmal L-type calcium channel in the cardiomyopathic Syrian hamster. The
      mechanism of action of verapamil in the cardiomyopathic Syrian hamster remains to
      be elucidated.

PMID- 1380598
TI  - Na(+)-channel activators increase cardiac glycoside sensitivity in failing human
      myocardium.
AB  - Na(+)-channel activators increase intracellular Na+ and thereby enhance the
      transport rate of sarcolemmal Na+,K(+)-ATPase. We investigated the interaction of
      the new Na(+)-channel activator BDF 9148 (BDF) with the cardiac glycoside ouabain
      (OUA) in human myocardium. The influence of OUA (0.01-0.1 microM) and of OUA
      after prestimulation with BDF (0.1 microM, 1 microM; BDF+OUA) on isometric force
      of contraction (FOC, force of contraction; +T/-T, peak rate of tension
      increase/decay) of electrically driven (1 Hz, 37 degrees C) papillary muscle
      strips from terminally failing [New York Heart Association classification IV
      (NYHA IV) heart transplants, n = 19] human myocardium was studied. We also
      examined the effects of BDF and OUA on nonfailing human myocardium (brain death
      resulting from traumatic injury, n = 5). 0.01 microM OUA enhanced FOC only after
      prestimulation with BDF (NYHA IV+2.9 +/- 0.4 mN; p less than 0.01). The time
      until maximal (Tmax: BDF+OUA 117 min, OUA 166 min), half-maximal (T1/2max:
      BDF+OUA 47 min, OUA 85 min) inotropic effects and time until toxic signs
      (contracture, extrasystoles) occurred were significantly shorter with BDF+OUA as
      compared with OUA alone. BDF influenced Tmax, T1/2max, and time until toxic side
      effects occurred (Ttox) of the OUA-mediated inotropism in a concentration
      dependent manner. Both OUA and BDF enhanced +T and -T. The effectiveness of OUA
      and BDF in increasing FOC was similar to that of Ca2+ (1.8-15 mM) but
      significantly (p less than 0.01) higher as compared with the beta-adrenoceptor
      agonist isoprenaline in NYHA IV. In myocardial membranes, [3H]ouabain binding
      (Bmax, Kd) was not affected by BDF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380599
TI  - The interrelationship between the effects of captopril and nifedipine on pressor
      responses elicited by selective alpha-adrenoceptor agonists in the pithed rat
      preparation.
AB  - The interrelationship between the effects of the angiotensin converting enzyme
      inhibitor captopril and the calcium channel antagonist nifedipine on alpha
      mediated vasoconstriction elicited by the administration of the full and partial
      alpha 1-adrenoceptor agonists St 587 and cirazoline, respectively, and the alpha
      2-adrenoceptor agonist B-HT 920 were examined in pithed normotensive rats.
      Treatment with captopril was found to attenuate pressor responses produced by the
      administration of either alpha 1- or alpha 2-adrenoceptor agonists, resulting in
      the displacement to the right of the agonist dose-response curves and
      significantly increasing the calculated ED50 values. The maximum response was
      unaltered and the calculated dose ratios for alpha-agonists in the presence or
      absence of captopril were found to be 3, 4.6, and 3.8 for B-HT 920, St 587, and
      cirazoline, respectively. In comparison, nifedipine displaced the dose-response
      curves for all three alpha-agonists to the right but only significantly increased
      the ED50 values for the partial alpha 1-agonist St 587 and the alpha 2-agonist B
      HT 920, with the calculated dose ratios being 3.2 and 3.8, respectively.
      Following treatment with nifedipine, however, the maximum responses were
      significantly reduced. A combination of captopril and nifedipine did not result
      in any significant additive increase in the ED50 values compared to those
      obtained with captopril or nifedipine alone. However, the inhibition of the
      maximum response to B-HT 920 by a combination of captopril and nifedipine was
      additive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380600
TI  - Comparison of vasoconstrictor actions of endothelin-1 in cerebral, coronary, and
      mesenteric arteries of the dog.
AB  - Vasoconstrictor actions of endothelin-1 (ET) were compared between endothelium
      removed strips of cerebral (basilar, posterior cerebral, and middle cerebral) and
      peripheral (coronary and mesenteric) arteries of the dog. ET produced a
      concentration-dependent contraction in these arteries. A threshold concentration
      and EC50 value for ET were significantly lower in the basilar, posterior
      cerebral, middle cerebral, and coronary arteries than in the mesenteric artery.
      In the basilar artery, nifedipine caused a rightward displacement of the
      concentration-response curve for ET with a significant reduction in the maximum
      response to ET. On the other hand, nifedipine showed a typical noncompetitive
      antagonism against ET in the mesenteric artery. Contractile responses of the
      mesenteric artery to ET determined under an elevation of extracellular K+
      concentration were comparable to the responses of the basilar artery to this
      peptide determined under normal K+ concentrations. The cerebral and coronary
      arteries, but not the mesenteric artery, relaxed significantly from the resting
      level when placed in a Ca(2+)-free solution containing 0.1 mM EGTA (0-Ca
      solution). The readdition of Ca2+ to the cerebral and coronary arteries soaked in
      the 0-Ca solution caused a biphasic contraction that was susceptible to
      inhibition by nifedipine. When ET in concentrations below 10(-9) M was introduced
      before the Ca(2+)-induced contraction, this peptide produced no detectable
      contraction, but potentiated the Ca(2+)-induced contraction. The extent of
      potentiation induced by ET was much greater in the cerebral and coronary arteries
      than in the mesenteric artery. Even in the 0-Ca solution, higher concentrations
      of ET (1 x 10(-8) and 3 x 10(-8) M) produced a contraction that was weaker in the
      basilar artery than in the mesenteric artery. These results indicate that the
      cerebral and coronary arteries exhibited more potent contractions in response to
      lower concentrations (below 10(-9) M) of ET than the mesenteric artery. A likely
      possibility for these enhanced responses to ET in the cerebral and coronary
      arteries appears to be that the voltage-dependent Ca2+ channels in these arteries
      are more activated in the resting state than those in the mesenteric artery.

PMID- 1380601
TI  - Effect of epinine on systemic hemodynamics and regional blood flow in conscious
      pigs.
AB  - Intravenous (i.v.) infusions (1, 2.5, 5, and 10 micrograms/kg/min for 10 min)
      were used to evaluate the cardiovascular effects of epinine (N-methyl-dopamine)
      in 8 conscious pigs. Epinine is a nonselective and nonspecific dopamine (DA)
      agonist, that also stimulates alpha- and beta-adrenoceptors. Epinine (1-5
      microgram/kg/min) increased cardiac output (CO) by up to 15 +/- 5% (p less than
      0.05), owing to an increase in heart rate (HR, 24 +/- 6%), but an increase in
      stroke volume (SV, 16 +/- 4%) caused the further increase in CO at 10
      micrograms/kg/min. Mean arterial blood pressure decreased gradually from 100 +/-
      5 mm Hg to 84 +/- 4 mm Hg during infusions up to 5 microgram/kg/min, but
      increased to 89 +/- 4 mm Hg during infusion of 10 micrograms/kg/min (p less than
      0.05). Systemic vascular resistance had decreased from 36.5 +/- 2.8 to 27.5 +/-
      3.0 mm Hg/L/min after infusion of 5 micrograms/kg/min but did not change further
      during infusion of 10 micrograms/kg/min. LV dP/dtmax increased only at 10
      micrograms/kg/min. Myocardial blood flow did not change at any dose, owing to
      metabolically regulated coronary vasodilatation (myocardial work did not change).
      Flow to the adrenals (up to 110 +/- 37%) and the spleen (up to 95 +/- 13%)
      increased dose dependently. Cerebral blood flow increased only at the highest
      dose (15 +/- 5%, p less than 0.05); flow to the kidneys, liver, small intestine,
      and skeletal muscle did not change. Flow decreased to the stomach (21 +/- 5%) and
      skin (for doses less than 2.5 micrograms/kg/min).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1380602
TI  - Nonadrenergic sympathetic vascular control of the human forearm in hypertension:
      possible involvement of neuropeptide Y.
AB  - Animal experimental evidence suggests that neuropeptide Y (NPY) is coreleased
      with norepinephrine (NE) from sympathetic nerve endings and is involved in
      nonadrenergic neurogenic vascular control of skeletal muscle. We wished to
      determine whether these findings may be extended to humans. Forearm blood flow
      (venous occlusion plethysmography) and the regional overflows of NE and NPY-like
      immunoreactivity (NPY-LI) were studied at rest and during sympathetic nerve
      activation by lower body negative pressure (LBNP; -10 mm Hg, 10 min) in 10
      hypertensive men before and after local alpha-adrenergic blockade by a dose of
      phenoxybenzamine (60 micrograms x 100 ml-1 x min-1 for 60 min), which most
      markedly attenuated responses to exogenous NE; propranolol (10 micrograms x 100
      ml-1 x min-1) was present throughout. Phenoxybenzamine increased forearm blood
      flow at rest (11.5 +/- 1.0 vs. 3.9 +/- 0.3 ml x 100 ml-1 x min-1; p less than
      0.001). LBNP-evoked reduction of forearm blood flow (37 +/- 2%, p less than
      0.001) was attenuated (p less than 0.001) but not abolished (18 +/- 2%, p less
      than 0.001) by phenoxybenzamine. LBNP increased the overflow of NE from 5.0 +/-
      1.7 to 8.2 +/- 3.0 pmol x 100 ml-1 x min-1 (p less than 0.05) and that of NPY-LI
      from -9.0 +/- 4.4 to 8.0 +/- 4.9 fmol x 100 ml-1 x min-1 (p less than 0.05) after
      phenoxybenzamine; effects on the evoked overflows of NE and NPY-LI before
      phenoxybenzamine were slight. Prejunctional inhibitory alpha-adrenoceptors may
      thus modulate NPY release as well.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380603
TI  - Potential cellular mechanisms of hydrogen peroxide-induced cardiac arrhythmias.
AB  - The electrophysiologic effects of hydrogen peroxide on the isolated guinea pig
      right ventricular free wall were studied using simultaneous recordings of action
      potentials from the epicardium and the endocardium. Exposure to hydrogen peroxide
      caused a time- and concentration-dependent change in action potential
      characteristics. Action potential durations at 50 and 90% of repolarization
      (APD50 and APD90, respectively) were significantly prolonged by hydrogen peroxide
      in both the epicardium and the endocardium. Although prolongation occurred at
      lower concentrations (0.5 mM) in the epicardium, increases in APD in response to
      higher concentrations of hydrogen peroxide (1 or 4 mM) were maintained for a
      longer period of time in the endocardium. In addition, hydrogen peroxide (1 or 4
      mM) caused significant depolarization in the epicardium after 10 min, although
      this effect was observed only in the endocardium exposed to 4 mM hydrogen
      peroxide. Ventricular arrhythmias were observed in 5 of 7, 6 of 7, and 7 of 7
      preparations exposed to 0.5, 1, and 4 mM hydrogen peroxide, respectively. The
      most frequently observed electrophysiologic abnormalities were associated with
      increased automaticity. Coupled beats, including clearly identifiable early and
      delayed depolarizations, were also observed. Verapamil (2 microM) and amiloride
      (0.1 mM) reduced both the incidence and the duration of hydrogen peroxide-induced
      arrhythmias but did not influence the effects on APD. This study is the first
      demonstration of hydrogen peroxide-mediated transmural dispersion in APD that
      could play an important role in the development of ventricular arrhythmias. In
      addition, our results demonstrate that hydrogen peroxide can induce ventricular
      arrhythmias through several cellular mechanisms, including increased
      automaticity, coupled beats, and triggered activity.

PMID- 1380604
TI  - Effects of chronic treatment with SQ29852 on spontaneous smooth muscle tone and
      endothelium-dependent relaxation in aorta of stroke-prone spontaneously
      hypertensive rats.
AB  - The effects of chronic treatment with SQ29852, an angiotensin-converting enzyme
      inhibitor, on spontaneous smooth muscle tone and endothelium-dependent relaxation
      of aorta from stroke-prone spontaneously hypertensive rats (SHRSP) were studied
      and compared with those of captopril. Endothelium-removed aorta from 16-week-old
      SHRSP exhibited a high amplitude of spontaneously developed active tension
      (active tone), whereas no active tone was observed in the preparation from
      control normotensive Wistar-Kyoto (WKY) rats. Treatment with SQ29852 or captopril
      at age 5-16 weeks prevented the development of hypertension. No active tone could
      be detected in the preparation from SQ29852-treated SHRSP. Endothelium-dependent
      relaxation was markedly reduced in the preparation from nontreated SHRSP compared
      with WKY rats. Treatment with SQ29852 prevented the impairment of endothelium
      dependent relaxation. It was also shown that norepinephrine-induced contraction
      was markedly depressed in endothelium-intact aorta from SQ29852-treated rats. The
      effects of SQ29852 were more prominent than those of hydralazine when blood
      pressure was maintained at similar levels. It was suggested that SQ29852 exerts
      an action on both vascular smooth muscle and endothelium that is mediated by the
      inhibition of angiotension-converting enzyme in addition to indirect actions of
      SQ29852 that are brought about by blood pressure lowering.

PMID- 1380606
TI  - Inhibition by glibenclamide of negative chronotropic and inotropic responses to
      pinacidil, acetylcholine, and adenosine in the isolated dog heart.
AB  - The blocking effects of glibenclamide on the chronotropic and inotropic responses
      to K+ channel openers pinacidil (ATP-sensitive) and acetylcholine (ACh) or
      adenosine (receptor-operated) were investigated in the isolated, blood-perfused
      canine atrium or ventricle. Glibenclamide (0.1-3 mumol) induced no significant
      cardiac effects. Cumulative administration of pinacidil (0.03-3 mumol) dose
      dependently decreased sinus rate much less than the contractile force of the
      atrial and ventricular muscles. Glibenclamide similarly inhibited the negative
      chronotropic and inotropic responses to pinacidil in a dose-related manner. A
      high dose of glibenclamide (3 mumol) slightly but significantly attenuated the
      negative chronotropic and inotropic responses to ACh and adenosine but not to
      verapamil. These results demonstrate that glibenclamide inhibits the negative
      chronotropic and inotropic responses to the ATP-sensitive K+ channel opener
      pinacidil and the receptor-operated K+ channel openers ACh and adenosine but more
      selectively antagonizes the responses to pinacidil in the dog heart and suggest
      that in contrast to ACh and adenosine, an ATP-sensitive K+ channel opener has a
      greater effect on the ventricle than on the sinoatrial node.

PMID- 1380605
TI  - Radioligand binding and inotropic effects of ryanodine in the cardiomyopathic
      Syrian hamster.
AB  - We compared the radioligand-binding and inotropic effects of ryanodine [known
      specific regulator of sarcoplasmic reticulum (SR) calcium release channel] on BIO
      14.6 cardiomyopathic Syrian hamsters with those on age-matched F1B controls.
      Scatchard analyses of [3H]ryanodine binding to cardiac membranes prepared from 1
      2-month-old BIO 14.6 and F1B Syrian hamsters revealed the presence of a
      significant increase in binding capacity (Bmax = 942 +/- 49 vs. 567 +/- 33
      fmol/mg protein) with no difference in affinity (KD = 3.9 +/- 0.4 vs. 3.5 +/- 0.5
      nM, p less than 0.01). Ryanodine is a significantly less potent negative inotrope
      in isolated papillary muscles prepared from 1-2-month-old BIO 14.6 hamsters than
      in muscles from F1B controls (IC50 = 4.3 +/- 1 vs. 0.5 +/- 0.4 microM, p less
      than 0.05). Ryanodine was 200-fold less potent in the 4-6-month-old myopathic
      muscles than in controls (IC50 = 20 +/- 5 vs. 0.1 +/- 0.01 microM, p less than
      0.01). A paradoxic positive inotropic effect of ryanodine observed in 4-6-month
      old myopathic muscles at low concentrations was not seen in controls (ECmax = 126
      +/- 5% at 1 +/- 0.1 x 10(-8) M). These data support the presence of a defect both
      biochemical and physiologic in the ryanodine-sensitive SR calcium release channel
      in the BIO 14.6 cardiomyopathic Syrian hamster. Purification, cloning,
      sequencing, and expression studies will be required to distinguish among primary,
      secondary, intrinsic, and regulatory defects in the ryanodine-sensitive SR
      calcium release channel in the cardiomyopathic Syrian hamster.

PMID- 1380607
TI  - Cardiovascular and adenylate cyclase stimulant properties of NKH477, a novel
      water-soluble forskolin derivative.
AB  - The cardiovascular effects of NKH477 (6-(3-dimethylaminopropionyl)forskolin
      hydrochloride), a novel water-soluble forskolin derivative, were investigated in
      dogs. Intravenous (i.v.) injections of NKH477 (1-30 micrograms/kg) caused dose
      related increases in left ventricular dP/dtmax (LVdP/dtmax), coronary and femoral
      artery blood flow (CBF, FBF), heart rate (HR), and myocardial oxygen consumption
      (MVO2) and a dose-related decrease in blood pressure (BP) in anesthetized dogs.
      The regression analysis between CBF and MVO2 showed that NKH477 did not influence
      substantially the balance of oxygen supply and demand. Infusions of NKH477 (0.15
      0.6 microgram/kg/min i.v.) also increased LVdP/dtmax, cardiac output (CO), and HR
      and decreased BP, pulmonary arterial diastolic pressure, and total peripheral
      resistance (TPR) in a dose-dependent manner. In contrast to forskolin, NKH477
      administered intraduodenally (0.05-0.2 mg/kg) and orally (0.15 and 0.3 mg/kg)
      clearly exhibited cardiovascular actions, as it did in i.v. administration,
      indicating that NKH477 is orally active. No arrhythmias were induced by NKH477 in
      any study. NKH477, like forskolin, showed adenylate cyclase stimulant activity in
      guinea pig ventricular membrane but did not inhibit Na+, K(+)-ATPase or
      phosphodiesterase (PDE) activity. Thus, NKH477 can be characterized as a potent,
      orally active, water-soluble forskolin derivative, which suggests that NKH477 is
      a useful inodilator for treatment of heart failure, especially in the severe
      stage with beta-adrenoceptor downregulation.

PMID- 1380608
TI  - Acute hemodynamic, hormonal, and renal effects of neutral endopeptidase
      inhibition in ovine heart failure.
AB  - The effects of neutral endopeptidase inhibition (NEP-I) were studied in 6
      conscious sheep with heart failure (HF) induced by rapid ventricular pacing for 7
      days. Measurements were performed 1 h before and for 6 h after intravenous (i.v.)
      bolus administration of vehicle and SCH 39370 (1.25 and 5 mg/kg) on separate
      days. After the higher dose, an index of serum NEP activity decreased from 0.83
      +/- 0.05 to 0.13 +/- 0.07 nmol/ml/min (p less than 0.001) at 1 h and then
      returned to control levels at 6 h. Plasma atrial natriuretic peptide (ANP) and
      cyclic GMP rose from 328 +/- 28 and 20.2 +/- 4.3 to a peak of 570 +/- 65 pmol/L
      (p less than 0.001) and 28.7 +/- 6.3 nmol/L (p less than 0.05) respectively.
      Natriuresis and diuresis were significant and left atrial pressure (LAP)
      decreased from 21.9 +/- 1.1 to 20.1 +/- 0.8 mm Hg (p less than 0.05). Despite
      high endogenous ANP levels in HF, NEP-I further increases both ANP and its
      "second messenger." Its natriuretic and hemodynamic effects are consistent with
      enhanced ANP activity in renal and vascular tissues, suggesting that NEP-I may be
      useful for treating HF.

PMID- 1380609
TI  - Mechanism of nitrate-induced improvement on arterial compliance depends on
      vascular territory.
AB  - The link between arterial caliber and distensibility has been studied
      extensively, with conflicting results. As have other researchers, we previously
      showed evidence of an increase in arterial diameter and a decrease in arterial
      stiffness with use of nitrates at the site of the brachial artery (BA) and the
      aorta. Whether these results would apply to other large superficial arteries
      remained to be established. In the present study, by means of an original pulsed
      ultrasound echo-tracking system based on Doppler shift, we measured internal
      diastolic diameter and stroke change in diameter of the common carotid artery
      (CCA), the femoral artery, and the BA in patients with essential hypertension and
      determined the acute effects of administration of isosorbide dinitrate (ISDN 20
      mg). Twenty untreated hypertensive patients entered this randomized, placebo
      controlled, double-blind, parallel study. No significant change occurred during
      placebo. During ISDN therapy, blood pressure (BP) decreased significantly; cross
      sectional compliance increased at the site of the CCA, the BA, and the common
      femoral artery (CFA). The increase in cross-sectional compliance was mainly due
      to an increase in internal diameter for CCA and to an increase in distensibility
      coefficient (DC) for BA. The pattern of cross-sectional compliance was
      intermediate for CFA. During ISDN therapy, the augmentation index of the CCA
      distension waveform was significantly reduced, whereas no change occurred during
      placebo, suggesting a reduction in wave reflection by nitrates.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1380610
TI  - Treatment of transient myocardial ischemia in patients with stable angina: a
      comparative study of verapamil slow-release and nifedipine plus propranolol.
AB  - We compared the effect of verapamil slow-release (VSR) and the combination of
      nifedipine plus propranolol on transient myocardial ischemia in a double-blind
      study comprising 20 patients with proven coronary artery disease and chronic
      stable angina. According to the results of 24-h Holter-monitoring recording,
      patients were divided into two groups: 10 patients with fixed coronary reserve
      and 10 patients with variable coronary reserve. The number of ischemic events was
      reduced with both therapies: from 12 +/- 10 at baseline to 3.4 +/- 4.0 (p less
      than 0.05) with verapamil and to 3.9 +/- 7.0 (p less than 0.05) with nifedipine
      plus propranolol (N + P). When total ischemic burden was measured, findings were
      similar: It was reduced from 104 +/- 196 min to 27 +/- 57 (p less than 0.05) with
      N + P and to 17 +/- 18 min with verapamil in patients with fixed coronary reserve
      and from 36 +/- 44 to 5 +/- 9 min (p less than 0.05) with verapamil and to 5 +/-
      10 min with N + P in patients with a variable coronary reserve. VSR shows
      antiischemic efficacy similar to that of the combination of N + P in treatment of
      transient myocardial ischemia in patients with stable angina.

PMID- 1380611
TI  - Development and modulation of experimental right ventricular hypertrophy in rats.
AB  - Two models of right ventricular (RV) hypertrophy in rats have been created and
      characterized: chronic myocardial infarction and pulmonary artery stenosis. A
      Millar ultraminiature catheter pressure transducer designed specifically for
      right heart catheterization was used for the measurement of RV function in closed
      chest, anesthetized rats. Four weeks after coronary artery ligation, left
      ventricular (LV) function was depressed as evidenced by the reduction of LV
      systolic pressure (LVSP), the maximal rate of rise in LV pressure (LV dp/dtmax),
      cardiac output, and by the elevation of LV end-diastolic pressure (LVEDP). There
      was an increase in RVSP and an elevation in RV dp/dtmax as well as an increase in
      the RV weight/body weight ratio. Myocytes isolated from the RV 4 weeks after
      coronary artery ligation had a greater volume and cross-sectional area. In
      addition, 14 days after pulmonary artery stenosis, there also was an elevation in
      RVSP and in RV dp/dtmax. In this model, the effect of angiotensin-converting
      enzyme (ACE) inhibition with ramipril (1 mg/kg daily) was examined. The increase
      in RVSP from 35 +/- 2 to 61 +/- 4 mm Hg after pulmonary artery stenosis was not
      influenced by ramipril (63 +/- 4 mm Hg), neither was the elevation of RV weight.
      However, the increase in cell volume and cross-sectional area of myocytes
      isolated from the RV was less pronounced in the ramipril-treated group (+27%
      compared with +58% in untreated animals). Thus, ACE inhibition with ramipril
      altered the hypertrophic response at the cellular level.

PMID- 1380612
TI  - Cardiovascular hypertrophy: from molecular biology to clinics, therapy, and
      prevention. Franz Gross Hypertension Symposium. Kronberg, March 7-9, 1991.

PMID- 1380613
TI  - Morphometric investigation of intramyocardial arterioles in right septal
      endomyocardial biopsy of patients with arterial hypertension and left ventricular
      hypertrophy.
AB  - A reduced maximal coronary vasodilatator capacity is reported in patients with
      hypertensive heart disease, suggesting structural abnormalities of
      intramyocardial arterioles. Right septal endomyocardial catheter biopsies (EMCB)
      of 30 patients with arterial hypertension and of 10 heart donors were
      investigated morphometrically. In hypertension, the mean external diameter (21.9
      +/- 3.0 vs. 17.4 +/- 2.9 microns, p less than or equal to 0.01) of arterioles and
      the mean arterial wall area (284 +/- 80 vs. 167 +/- 69 microns2, p less than or
      equal to 0.05) were increased as compared with heart donors. Perivascular
      fibrosis was markedly increased (260 +/- 183 vs. 41 +/- 30 microns2, p less than
      or equal to 0.05) as well as volume density of fibrosis (3.0 +/- 1.7 vs. 0.9 +/-
      0.8 Vv%, p less than or equal to 0.01) in hypertensive heart disease. There was
      no significant correlation between echocardiographically determined left
      ventricular mass index (115 +/- 25 g/m2 for men and 104 +/- 12 g/m2 for women)
      and mean arteriolar wall area (r = +0.17) or volume density of fibrosis (r =
      +0.2) in hypertensive heart disease. Our investigations show that in patients
      with arterial hypertension there is a thickening of intramyocardial arteriolar
      walls and an increase in fibrosis. Intramyocardial vascular alterations seem to
      manifest in hypertension independent from left ventricular hypertrophy.

PMID- 1380614
TI  - Cyclic GMP-dependent protein kinase and smooth muscle relaxation.
AB  - Cyclic guanosine monophosphate (cGMP)-dependent protein kinase has been cloned
      from bovine trachea. The isozymes I alpha and I beta, which differ only in their
      amino-terminal domains were expressed transiently in COS-7 cells. Both isozymes
      were activated by cGMP and cyclic adenosine monophosphate (cAMP). However,
      approximately 10-fold higher concentrations of cyclic nucleotides were needed to
      activate the I beta enzyme than the I alpha enzyme. The KA values for cAMP were
      9.1 and greater than 20 microM for the I alpha and I beta isozymes, respectively.
      It is therefore unlikely that an unmodified I beta enzyme that occurs in high
      concentrations in vascular smooth muscle can be activated in vivo by cAMP.

PMID- 1380615
TI  - Molecular biology of the coronary vascular and myocardial responses to ischemia.
AB  - To understand the complex mechanism(s) involved in molecular responses to
      ischemia, we developed two experimental models in pigs. In a "stunning" model of
      repetitive ischemia and reperfusion, we studied the mRNA expression of immediate
      early genes like c-fos, c-myc and heat shock protein-70 (HSP-70). Myocardial
      stunning was achieved by two cycles of 10-min left anterior descending coronary
      artery (LAD) occlusion and 30 min reperfusion. We observed several-fold enhanced
      expression of c-fos and HSP-70 mRNA in the stunned myocardium as compared with
      the control, whereas c-myc mRNA levels remained almost unchanged. In the second
      model, we examined the expression of the peptide mitogens heparin-binding growth
      factor 1 (HBGF-1) and transforming growth factor beta 1 (TGF-beta 1) after a
      chronic coronary artery occlusion leading to myocardial collateralization.
      Progredient stenosis of the circumflex coronary artery was induced by implanting
      a hygroscopic ameroid constrictor ring around it and occlusion was verified by in
      vivo angiography. Using polymerase chain reaction (PCR) and Northern
      hybridization techniques, we observed significantly enhanced expression of HBGF-1
      and TGF-beta 1 in collateralized myocardium as compared with normal. In situ
      techniques revealed the localization of HBGF-1 transcripts in the blood vessel
      wall, and TGF-beta 1 in cardiac myocytes and Purkinje cells. Our results clearly
      indicate that myocardial stunning stimulates the expression of transcription
      factors which might be involved in regulation of certain growth factors like HBGF
      1 and TGF-beta 1 which may play a significant role in the development of a
      collateral circulation.

PMID- 1380616
TI  - Medical repair of hypertensive left ventricular remodeling.
AB  - Hypertensive left ventricular (LV) hypertrophy leads to myocytic hypertrophy,
      interstitial fibrosis, and structural alterations of the coronary
      microcirculation. This structural remodeling of the myocardium results in an
      impairment of diastolic function of the left ventricle and of coronary flow
      reserve despite normal epicardial arteries. Consequently, an antihypertensive
      treatment should aim at (a) reversing myocytic hypertrophy, (b) regression of
      myocardial fibrosis, and (c) improvement of coronary flow reserve apart from
      blood pressure lowering. In recent years many clinical studies have shown that
      regression of hypertensive hypertrophy can be induced by long-term treatment with
      angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, beta
      receptor blockers, and antisympathonic drugs. However, vasodilators and
      diuretics, which stimulate adrenoceptor activity and increase angiotensin II
      levels, were found to be less effective in reversing LV hypertrophy. The trophic
      influence of catecholamines and angiotensin II on the myocardium counteracts the
      effect of systolic wall stress reduction due to blood pressure lowering. In
      respect of reversal of interstitial fibrosis, ACE inhibitors seem to be effective
      because the growth of fibroblasts was found to be stimulated by angiotensin II.
      Recently, clinical studies have confirmed previous experimental data that an
      improvement of the impaired coronary vasodilator reserve can be realized by long
      term antihypertensive therapy. An antihypertensive treatment strategy which fully
      restores myocardial structure and completely repairs coronary microcirculation
      has to be considered as a causative treatment of hypertensive heart disease.

PMID- 1380617
TI  - The role of angiotensin II in vascular smooth muscle cell growth.
AB  - One of the major consequences of hypertension is an increase in the thickness of
      the arterial medial smooth muscle cell layer. This has been shown in both large
      and medium size resistance vessels caused by smooth muscle cell hypertrophy. Both
      in vivo and in vitro data suggest that the vasoconstrictor peptide angiotensin II
      (Ang II) may play an important role in the development of the smooth muscle
      hypertrophy. We have demonstrated that Ang II, when added to quiescence cultures
      of vascular smooth muscle cells, results in the rapid induction of the early
      growth response genes c-fos, c-myc, and c-jun. This is due to new transcription
      as demonstrated by nuclear runoff transcription assay, but is not dependent on
      new protein synthesis, as it is not blocked by the addition of cycloheximide. The
      effect is due, however, to an increase in intracellular calcium, suggesting that
      any vasoconstrictor which results in an increase in intracellular calcium may act
      in this manner. Following the induction of the early growth response genes there
      is delayed induction of the platelet derived growth factor A-chain gene. Data
      from our laboratory and from that of others has shown in preliminary studies that
      blockade of either the Ang II-induced increases in c-fos or in the platelet
      derived growth factor A-chain increases smooth muscle cell protein synthesis.
      This suggests that Ang II and other vasoconstrictors may play an important role
      in vascular smooth muscle growth, in hypertension and also in atherosclerosis and
      following balloon injury of the arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380618
TI  - Left ventricular remodeling after myocardial infarction: does the cardiac renin
      angiotensin system play a role?
AB  - Possible cardioprotective effects are one of the most intriguing aspects of the
      expanding spectrum of clinical indications for the use of converting-enzyme
      inhibitors. Among them, the prevention of postinfarction ventricular remodeling-
      a deleterious process leading to eccentric cardiac hypertrophy and, eventually,
      to congestive heart failure--has attracted particular interest and attention.
      This communication examines the possible role of the endogenous cardiac renin
      angiotensin system in the pathophysiology of ventricular remodeling. Although
      much of the evidence is indirect, there are several lines of investigation that
      strongly support the causative participation of the cardiac renin-angiotensin
      system in ventricular remodeling.

PMID- 1380619
TI  - Myocardial fibrosis and the renin-angiotensin-aldosterone system.
AB  - In both men and women left ventricular hypertrophy (LVH) is the major risk factor
      associated with the appearance of diastolic and/or systolic myocardial failure.
      It is not the growth of cardiac myocytes, however, that is responsible for an
      abnormal structural remodeling of the hypertrophied myocardium in pathologic LVH,
      but instead, nonmyocyte cells whose behavior and growth are altered by chronic
      elevations in circulating hormones. Hormone-mediated cardiac fibroblast
      proliferation and/or enhanced collagen synthesis, for example, account for
      myocardial fibrosis. The signals mediating nonmyocyte cell involvement in LVH may
      also involve locally generated hormones having paracrine properties. Herein we
      review experimental findings pertaining to the reparative and reactive fibrosis
      of the myocardium seen in various forms of acquired and genetic arterial
      hypertension, where circulating or tissue renin-angiotensin-aldosterone systems
      are respectively activated. These hormonal systems determine whether myocardial
      structure will be altered in arterial hypertension and, accordingly, if
      myocardial failure ensues. The mechanisms by which these hormones lead to
      myocardial fibrosis remain to be elucidated and correspondingly will determine if
      fibrosis can be effectively prevented. At the same time, experimental strategies
      that regress excess collagen in LVH have been identified, but need to be
      developed further to determine if myocardial failure, caused by fibrosis, is
      indeed reversible in humans.

PMID- 1380620
TI  - Vasoactive peptides and growth factors in the pathophysiology of hypertension.
AB  - A hallmark of vascular disease is the inappropriate proliferative and synthetic
      behavior of smooth muscle cells. This phenotypically immature behavior arises as
      a consequence of the myocytes undergoing conversion from a contractile to
      proliferative/secretory cell type. The stimulus invoked for this
      dedifferentiative process has been, until recently, endothelial desquamation and
      subsequent acute exposure of the smooth muscle cells to platelet-derived
      mitogens. Pathogenic conversion of myocytes occurs even in the absence of damage
      to the endothelium, however, and therefore normal components of blood vessels are
      implicit in this process. These include vasoconstrictor and growth factor
      peptides, as well as extracellular matrix molecules and associated compounds such
      as low-density lipoproteins. In vitro experimentation has indicated a number of
      compounds that, individually, are only mild stimulators of smooth muscle
      proliferative metabolism but which combine synergistically to induce robust
      responses. The enhanced proliferative metabolism exhibited by smooth muscle cells
      derived from the vessels of hypertensive animals, may arise as a consequence of
      their response to stimulation and/or to perturbation of the mechanisms involved
      in the inhibition of growth. In vitro experimental models such as the co-culture
      of smooth muscle and endothelial cells will facilitate definition of the
      influence of the endothelium on the processes that lead to smooth muscle
      conversion and modulated gene expression.

PMID- 1380621
TI  - Vascular growth in hypertension.
AB  - This article discusses some of the mechanisms controlling the development of the
      vasculature. The process is complex, and the result makes it possible for the
      cardiovascular system to supply each tissue with the required amount of blood at
      the correct pressure. In general, the changes appear to be adaptive, such that
      the vessels perform their tasks more effectively. Increasing flow appears to be a
      powerful stimulus to growth, resulting in an increased lumen, whereas raised
      pressure is associated with an increased media: lumen ratio, which in human
      essential hypertension may be caused by remodeling (rearrangement of otherwise
      normal cells) rather than vascular growth. Thus, the physical environment
      (intravascular flow and pressure) plays an important role in determining vascular
      structure. This suggests that an important aspect of future research will be to
      understand more closely the mechanism by which the physical factors can stimulate
      growth, a process that must presumably be mediated by proto-oncogenes.

PMID- 1380622
TI  - [Granulocyte colony-stimulating factor in a patient with toxic neutropenia and
      acquired immunodeficiency syndrome].

PMID- 1380623
TI  - [Unfortunately, lack of judgement is not unusual].

PMID- 1380624
TI  - [Alzheimer's disease, growth disorders, pain... Galanin--a new peptide in front
      line research. Interview by Bigit Wilhelmson].

PMID- 1380625
TI  - [Recurrent infections should be investigated with consideration to primary
      immunodeficiency].

PMID- 1380626
TI  - Transmission of Pseudomonas cepacia among cystic fibrosis patients.

PMID- 1380627
TI  - Aprotinin and orthotopic liver transplantation.

PMID- 1380628
TI  - The extent of Down's syndrome screening in Britain in 1991.

PMID- 1380630
TI  - Finasteride for benign prostatic hypertrophy.

PMID- 1380629
TI  - [Atopic dermatitis. Clinical aspects, pathogenesis and therapy].

PMID- 1380631
TI  - [The identification of marker strains of Leishmania major, L. turanica and L.
      gerbilli by the polymer chain reaction with a universal primer].
AB  - The Leningrad Nuclear Physics Institute, Academy of Science of the USSR, and
      Martsinovskii Institute of Medical Parasitology and Tropical Medicine, USSR
      Ministry of Health, developed polymerase chain reaction (PCR) technique with
      universal primer 3-2 for Leishmania identification. The primers were patented in
      the USSR (Patent No 4757254, 1989). Reference strains of three Leishmania species
      were identified: L. major--MRHO/SU/59/Neal P; L. gerbilli--MRHO/CN/60/gerbilli;
      L. turanica--MRHO/SU/80/Cl 3720 and MRHO/SU/83/KD 051. Each Leishmania species is
      specific and different in its PCR pattern whereas the two L. turanica strains
      have identical PCR patterns of the given primer.

PMID- 1380633
TI  - [Postoperative changes in acute phase protein in patients with esophageal
      cancer].
AB  - Thirty-three patients with esophageal cancer were studied to assess the
      relationship between nutritional state and the acute phase protein responses.
      Blood samples taken preoperatively and days 1, 4, 7 and 14 after operation were
      analyzed for C-reactive protein, fibrinogen, alpha 1-antitrypsin, alpha 1-acid
      glycoprotein and haptoglobin. Significant Spearman's coefficients were found
      between percent of ideal body weight (IBW) and alpha 1-acid glycoprotein (r = 
      0.42), between prealbumin and alpha 1-anti-trypsin (r = -0.55), and between
      retinol-binding protein and alpha 1-antitrypsin (r = -0.51). Postoperatively, the
      levels of C-reactive protein, fibrinogen, alpha 1-anti-trypsin and alpha 1-acid
      glycoprotein were significantly lower in the poorly nourished group than in the
      other groups. The changes of acute phase proteins in the immediate postoperative
      period were affected by the preoperative nutritional state, and were less marked
      in the poorly nourished patients. Between two groups of patients in whom lymph
      node dissection was carried out in 2 or 3 areas, no significant differences were
      observed in the acute phase protein responses postoperatively. The measurement of
      acute phase proteins is very important in assessing the body defense capacity of
      the patient, but it should be noted that the changes may be affected by several
      factors including malnutrition.

PMID- 1380632
TI  - [Interferon status and the HLA antigen system. 1. Unilocular echinococcosis].
AB  - In 26 patients with hydatid disease interferons (IFN) blood levels by titration
      method and HLA-antigens by lymphocyte cytotoxicity microtest were estimated. In
      total group B5 antigen frequency was significantly (p = 0.007 after Fischer)
      higher than in the control group of 155 practically healthy persons: 38.5% and
      14.7% respectively. The determination of possible correlation between IFN-alpha
      and IFN-gamma production, HLA-antigens specificity and the localisation of
      Echinococcus granulosus cysts showed that in hydatid disease A2 and B5 antigens
      carriers are significantly stronger producers of the cytokines as compared with
      patients having A3 and B13 antigens. The highest titers of IFN-alpha was found in
      A2 antigen carriers with the liver cysts, the highest level of IFN-gamma had B5
      antigen carriers with the lung damage. A3 and B13 antigens carriers had low IFN
      titers independently of the character of damaged organ. Relatively high IFN-gamma
      blood titers in B5 antigen carriers with the lung cysts, persons predisposed to
      hydatid disease, permit supposing the stimulation of the cytokine production by
      the parasite for cysts formation in the lungs.

PMID- 1380634
TI  - [Immunohistochemical study and biodistribution of monoclonal antibody (Nd2)
      against human pancreatic cancer].
AB  - Nd2 was a murine monoclonal antibody produced against a mucin fraction purified
      from xenografts of the human pancreatic cancer cell line SW1990. The reactivity
      of Nd2 was reduced by trypsin, but was not influenced by neuraminidase, so the
      epitope recognized by Nd2 may involve peptide but not sialic acid. The antigen
      recognized by Nd2 was present in 83% of pancreatic cancer, whereas in tissue of
      normal pancreas and chronic pancreatitis no reactivity was detected. By
      biodistribution study, tumor/blood ratio was elevated 8.27 on the 7th day after
      injection of 125I-labeled Nd2, while tissue/blood ratio in liver was remained
      0.53. These results indicate that Nd2 had possibilities in clinical application
      such as radio-immunodetection and targeting therapy of pancreatic cancer.

PMID- 1380635
TI  - B-cell epitopes on autoantigens in connective tissue disease.

PMID- 1380636
TI  - Protein antigenicity.

PMID- 1380637
TI  - Molecular mimicry and autoantigens in connective tissue diseases.

PMID- 1380638
TI  - Methods of epitope mapping.

PMID- 1380639
TI  - Mapping of epitopes recognized by anti-(U1)RNP autoantibodies.

PMID- 1380640
TI  - B-cell epitopes of Sm autoantigens.

PMID- 1380641
TI  - B-cell epitopes of La and Ro autoantigens.

PMID- 1380642
TI  - B-cell epitopes of scleroderma-specific autoantigens.

PMID- 1380643
TI  - B-cell epitopes of autoantigenic DNA-binding proteins.

PMID- 1380644
TI  - B-cell epitopes of RNA autoantigens.

PMID- 1380645
TI  - [Cloning and expression in Escherichia coli of reverse transcriptase coded by the
      mobile genetic element jockey].
AB  - The mobile element jockey is similar in structural organization and coding
      potential to the LINEs of various organisms. Current models of the mechanism of
      transposition involve reverse transcription of an RNA intermediate and
      utilization of element-encoded proteins. As it is demonstrated here, a 2.23 kb
      DNA fragment from the region of the jockey encoding the putative reverse
      transcriptase, was stably introduced into the expression system under inducible
      control of the Escherichia coli lac regulatory elements. We describe the
      expression of the 92 kDa protein and identify this polypeptide alone as authentic
      jockey reverse transcriptase based on some of its physical and enzymic
      properties. The jockey polymerase demonstrates RNA-directed and DNA-directed DNA
      polymerase activities, but lacks detectable RNase H, has a temperature optimum at
      26 degrees C, requires Mg2+ or Mn2+ as a cofactor and is inactivated by
      sulfhydryl reagent. The enzyme prefers poly(rC) and poly(rA) as template and
      "activated" DNA is not effective. The results of this work suggest that the RNA
      directed DNA polymerase coded by jockey elements may be involved in the
      transcription of the elements.

PMID- 1380646
TI  - Increased gene-specific repair of cisplatin interstrand cross-links in cisplatin
      resistant human ovarian cancer cell lines.
AB  - We have studied several aspects of DNA damage formation and repair in human
      ovarian cancer cell lines which have become resistant to cisplatin through
      continued exposure to the anticancer drug. The resistant cell lines A2780/cp70
      and 2008/c13*5.25 were compared with their respective parental cell lines, A2780
      and 2008. Cells in culture were treated with cisplatin, and the two main DNA
      lesions formed, intrastrand adducts and interstrand cross-links, were quantitated
      before and after repair incubation. This quantitation was done for total genomic
      lesions and at the level of individual genes. In the overall genome, the initial
      frequency of both cisplatin lesions assayed was higher in the parental than in
      the derivative resistant cell lines. Nonetheless, the total genomic repair of
      each of these lesions was not increased in the resistant cells. These differences
      in initial lesion frequency between parental and resistant cell lines were not
      observed at the gene level. Resistant and parental cells had similar initial
      frequencies of intrastrand adducts and interstrand cross-links in the
      dihydrofolate reductase (DHFR) gene and in several other genes after cisplatin
      treatment of the cells. There was no increase in the repair efficiency of
      intrastrand adducts in the DHFR gene in resistant cell lines compared with the
      parental partners. However, a marked and consistent repair difference between
      parental and resistant cells was observed for the gene-specific repair of
      cisplatin interstrand cross-links. DNA interstrand cross-links were removed from
      three genes, the DHFR, multidrug resistance (MDR1), and delta-globin genes, much
      more efficiently in the resistant cell lines than in the parental cell lines. Our
      findings suggest that acquired cellular resistance to cisplatin may be associated
      with increased gene-specific DNA repair efficiency of a specific lesion, the
      interstrand cross-link.

PMID- 1380647
TI  - Hemimethylation and hypersensitivity are early events in transcriptional
      reactivation of human inactive X-linked genes in a hamster x human somatic cell
      hybrid.
AB  - Reactivation of the hypoxanthine phosphoribosyltransferase (HPRT) gene on an
      inactive human X chromosome in a somatic cell hybrid was analyzed following
      exposure to 5-aza-2'-deoxycytidine. Hemimethylation and chromatin
      hypersensitivity in the 5' CpG island appeared by 6 h after exposure and
      continued to increase for 24 h in an exponentially growing cell culture. These
      results imply that the conformation of inactive chromatin requires a
      symmetrically methylated 5' G+C-rich promoter region. In addition, quantitative
      analysis of the time course patterns suggest that chromatin sensitivity changes
      may depend on strand-specific demethylation. Symmetrically demethylated DNA was
      first detected at 24 h and continued to increase until 48 h. HPRT mRNA was first
      detected at 24 h and increased in a biphasic pattern until 48 h. These results
      suggest that hemimethylation permits nuclease attack but not transcription factor
      binding, which requires symmetrically demethylated DNA. We also show that in G1
      arrested cells, 5-aza-2'-deoxycytidine has no effect on methylation, chromatin
      conformation, or transcription. We conclude that reactivation of the HPRT gene
      present on the inactive X chromosome of a somatic cell hybrid involves the
      initial events of DNA hemimethylation and chromatin hypersensitivity at the 5'
      CpG island, followed by symmetrical demethylation and transcriptional
      reactivation.

PMID- 1380648
TI  - 5-Azacytidine treatment of HA-A melanoma cells induces Sp1 activity and
      concomitant transforming growth factor alpha expression.
AB  - Evidence indicates DNA methylation as a part of the regulatory machinery
      controlling mammalian gene expression. The human melanoma cell line HA-A
      expresses low levels of transforming growth factor alpha (TGF-alpha). TGF-alpha
      mRNA accumulated, however, in response to DNA demethylation induced by a
      nucleoside analog, 5-azacytidine (5-azaC). The importance of DNA methylation in
      the TGF-alpha promoter region was examined by a transient transfection assay with
      luciferase reporter plasmids containing a portion of the TGF-alpha promoter. 5
      azaC treatment of HA-A cells before the transfection caused a significant
      increase in the luciferase activity. Since input plasmids were confirmed to
      remain unmethylated, DNA demethylation of the TGF-alpha promoter itself does not
      account for the observed increase in TGF-alpha mRNA. Using an electrophoretic
      mobility shift assay, enhanced formation of protein-TGF-alpha promoter complex
      was detected in response to 5-azaC treatment. This 5-azaC-induced complex was
      shown to contain the transcription factor Sp1 by the following criteria: the
      protein-DNA complex formed on the TGF-alpha promoter contained immunoreactive
      Sp1; the mobility of the complex in an electrophoretic mobility shift assay was
      similar to that formed by recombinant Sp1; and DNase I footprinting analysis
      demonstrated that the 5-azaC-induced complex produced a footprint on the TGF
      alpha promoter identical to that of authentic Sp1. These observations suggest
      that 5-azaC induces TGF-alpha expression by augmenting the Sp1 activity. However,
      neither the Sp1 mRNA nor its protein was induced by 5-azaC. These results suggest
      that in HA-A cells, TGF-alpha expression is down-modulated by DNA methylation. In
      addition, this process may involve the specific regulation of Sp1 activity
      without altering the amount of the transcription factor.

PMID- 1380649
TI  - Translation of the rat LINE bicistronic RNAs in vitro involves ribosomal
      reinitiation instead of frameshifting.
AB  - The genomic structure of the rat LINE (L1Rn) DNA element contains two overlapping
      open reading frames (ORFs) and apparently has a potential to code for a DNA/RNA
      binding protein (in ORF1) and a reverse transcriptase (in ORF2). We have
      characterized a 1,630-bp L1Rn cDNA clone encompassing the overlapping ORFs and a
      600-bp genomic fragment derived from a full-length L1Rn member and containing the
      beginning of ORF1. These DNAs were used to restore in part the ORF1-ORF2
      organization of L1Rn after being cloned into the pSP65 vector under the control
      of SP6 polymerase promoter. To test whether L1Rn ORF1 and ORF2 are expressed as a
      fusion protein, a series of capped RNAs with progressive truncations containing
      one or both ORFs were prepared and translated in the rabbit reticulocyte lysate.
      Our analysis indicates that the expression of a putative reverse transcriptase
      encoded L1Rn ORF2 in vitro is regulated by reinitiation or internal initiation of
      translation but not by ribosomal frameshifting.

PMID- 1380650
TI  - Cell cycle progression in denV-transfected murine fibroblasts exposed to
      ultraviolet radiation.
AB  - Repair-proficient murine fibroblasts transfected with the denV gene of
      bacteriophage T4 repaired 70-80% of pyrimidine dimers within 24 h after exposure
      to 150 J/m2 ultraviolet radiation (UVR) from an FS-40 sunlamp. Under the same
      conditions, control cells repaired only about 20% of UVR-induced pyrimidine
      dimers. After UVR exposure, both control and denV-transfected cells exhibited
      some degree of DNA-synthesis inhibition, as determined by flow cytometric
      analysis of cell-cycle kinetics in propidium iodide-stained cells. DenV
      transfected cells had a longer and more profound S phase arrest than control
      cells, but both control and denV-transfected cells had largely recovered from UVR
      effects on cell-cycle kinetics by 48 h after UVR exposure. Inhibition of DNA
      synthesis by UVR was also measured by determining post-UVR incorporation of
      bromodeoxyuridine (BrdU). The amount of BrdU incorporated was quantitated by
      determining with flow cytometry the quenching of Hoechst dye 33342 by BrdU
      incorporated in cellular DNA. DenV-transfected cells showed more marked
      inhibition of BrdU incorporation after low fluences of UVR than control cells.
      Differences between denV-transfected and control cells in cell-cycle kinetics
      following UVR exposure may be related to differences in mechanisms of repair when
      excision repair of pyrimidine dimers is initiated by endonuclease V instead of
      cellular repair enzymes.

PMID- 1380651
TI  - Increased sensitivity of a Chinese hamster ovary cell line to alkylating agents
      after overexpression of the human metallothionein II-A gene.
AB  - The elevation of intracellular levels of metallothionein has been associated with
      the development of resistance to the cytotoxic effects of some alkylating agents.
      In order to study the mechanisms underlying metallothionein associated drug
      resistance we transfected the alkylating agent sensitive CHO cell line MMC-1
      (Robson et al., 1985) with an episomally replicating plasmid coding for the human
      metallothionein II-A gene. Two transfectants were isolated which carried about 10
      copies of the plasmid. The basal expression of metallothionein was increased from
      undetectable levels in the recipient cell line MMC-1 to between 22 and 26
      micrograms metallothionein per 10(7) cells in the transfectants. Treatment with
      cadmium salts increased metallothionein levels a further 1.7-fold. Cytotoxicity
      assays revealed that MTII-A transfection increased the sensitivity of the
      parental MMC-1 cells to N-methyl-N'-nitro-N-nitrosoguanidine and N-nitroso-N
      methylurea. These results suggest that metallothionein does not act as a simple
      scavenger of alkylating agents, but interacts with unknown factor(s) in host
      cells.

PMID- 1380652
TI  - Mutations affecting sensitivity of the cellular slime mold Dictyostelium
      discoideum to DNA-damaging agents.
AB  - We describe 22 new mutants of D. discoideum that are sensitive to DNA damage.
      These mutants were isolated on the basis of sensitivity to either temperature,
      gamma-rays, or 4-nitroquinolone-1-oxide (4NQO). The doses of gamma-rays,
      ultraviolet light (UV), and 4NQO required to reduce the survival of colony
      forming ability of these mutants to 10% (D10) range from 2% to 100% of the D10s
      for the nonmutant, parent strains. For most of the mutants, those which are very
      sensitive to one agent are very sensitive to all agents tested and those which
      are moderately sensitive to one agent, are moderately sensitive to all agents
      tested. One mutant is sensitive only to 4NQO. Linkage relationships have been
      examined for 13 of these mutants. This linkage information was used to design
      complementation tests to determine allelism with previously characterized
      complementation groups affecting sensitivity to radiation. 4 of the new mutants
      fall within previously identified complementation groups and 3 new
      complementation groups have been identified (radJ, radK and radL). Other new loci
      probably also exist among these new mutants. This brings the number of
      characterized mutants of D. discoideum which are sensitive to DNA-damaging agents
      to 33 and the number of assigned complementation groups to 11.

PMID- 1380653
TI  - Homologous recombination of adenovirus DNA in mammalian cells: enhanced
      recombination following UV-irradiation of the virus.
AB  - We have used adenovirus as a molecular probe to examine the recombination of
      viral DNA following infection of mammalian cells. The technique gives a
      quantitative measure of homologous recombination between adenovirus type 2 (Ad2)
      and Ad5PyMTR3. Ad5PyMTR3 is an insertion mutant of Ad5 containing polyoma virus
      (Py) DNA inserted into a deleted E1 region of the Ad5 genome. Cells were
      coinfected with Ad2 and Ad5PyMTR3 and at an appropriate time after infection,
      viral DNA was extracted from the infected cells, digested with restriction
      endonuclease and electrophoresed through an agarose gel. Although Ad2 and Ad5
      have more than 99% DNA homology, they differ sufficiently in their restriction
      endonuclease patterns, such that recombinant viral DNA molecules containing the
      Py insert could be detected and quantified by Southern blotting and hybridization
      to a radioactive Py DNA probe. Using this method we are able to detect and
      quantitate recombinant viral DNA molecules containing the Py insert which are
      present at frequencies down to at least 1 in 100. Recombination was detected in
      Chinese hamster ovary cells, monkey kidney cells, human HeLa cells, normal human
      fibroblasts and SV40 transformed human fibroblasts. In experiments using HeLa
      cells, the frequency of recombination between the Py insert on Ad5PyMTR3 and a
      number of unique restriction enzyme sites on Ad2 increased with the distance from
      the Py insert to the restriction site. Also in HeLa cells, recombination
      increased with increasing amounts of viral DNA synthesis and with increasing UV
      dose to the virus. UV-irradiation of both coinfecting viruses with 1500 J/m2
      resulted in a more than 100-fold reduction in the amount of viral DNA synthesized
      and about a 3-fold increase in the frequency of recombination.

PMID- 1380654
TI  - Xeroderma pigmentosum group A correcting protein from calf thymus.
AB  - A proteinous factor was purified from calf thymus and HeLa cells, which
      specifically corrects the excision repair defect of xeroderma pigmentosum
      complementation group A (XP-A) cells. Recovery of UV-induced unscheduled DNA
      synthesis after microinjection of XP-A cells was used as a quantitative assay for
      the correcting activity of protein preparations. XP-A correcting protein appears
      to be very stable as it withstands heating to 100 degrees C and treatment with
      SDS or 6 M urea. A molecular weight of 40-45 kD was found both under native (gel
      filtration) and denaturing (SDS-PAGE) conditions. Calf XP-A protein binds to
      single-stranded DNA more strongly than to double-stranded DNA, but shows no clear
      preference for UV-irradiated DNA. Polyclonal antibodies raised against human
      recombinant XP-A protein, which strongly inhibit UV-induced unscheduled DNA
      synthesis of normal human cells, completely abolished XP-A correcting activity
      when mixed with calf thymus preparations. This indicates a close relationship
      between human gene product and the calf protein. In the final preparation two
      main protein bands were present. Only one band at approx. 41 kD showed both DNA
      binding activity in Southwestern blots and immune reaction with human XP-A
      antibody, suggesting that this is the active calf XP-A correcting factor.

PMID- 1380655
TI  - Mammalian cells share a common pathway for the relief of DNA replication arrest
      by O6-alkyl guanine, incorporated 6-thioguanine and UV photoproducts.
AB  - We previously reported the cloning of a mammalian gene that restores UV
      resistance to a postreplication recovery defective and mex- Indian muntjac mutant
      cell line, SVM, by improving daughter-strand DNA replication on a UV-damaged
      template. The improved replication was, however, found to be error-prone, as
      judged by a hypermutable phenotype (Bouffler et al. (1990) Somatic Cell Mol.
      Genet., 16, 507-516). We now report that this gene also increases the resistance
      of SVM to the cytotoxic effects of methyl- and ethyl-nitrosourea, though not to
      dimethyl sulphate, by a similar postreplication recovery process. The gene does
      not increase the activity of O6-alkylguanine-DNA-alkyltransferase in the cell. We
      conclude that at least one mechanism of postreplication recovery in mammalian
      cells allows UV photoproducts and O6-alkylguanine lesions to be tolerated by the
      replication complex. The fact that the gene also confers resistance to 6
      thioguanine suggests that, once incorporated, this base analogue can disrupt
      normal DNA replication and that a single mechanism can allow replication to
      proceed beyond 3 diverse DNA lesions.

PMID- 1380656
TI  - Differential gene expression in wild-type and X-ray-sensitive mutants of Chinese
      hamster ovary cell lines.
AB  - Complementary DNA cloning, differential screening and Northern hybridization
      techniques were used to study differential gene expression in the wild-type
      Chinese hamster ovary (CHO) K1 cell line and its two X-ray sensitive mutants, xrs
      5 and xrs-6. 11 species of mRNAs were found underexpressed in the two
      independently isolated mutants. The steady-state levels of those mRNAs are 3-26
      fold less in the two mutants, depending on the particular species. 6 of the
      underexpressed mRNAs have been identified by comparing the sequences of the
      cloned cDNAs to the known sequences in GenBank. 4 of them code for the structural
      proteins of ferritin heavy chain, nonmuscle myosin light chain 3nm, ribosomal
      protein S17 and L7, respectively. The other two have strong homology with mouse
      B2 or retroviral sequences. The remaining 5 mRNAs did not show significant
      homology with any of the known sequences and apparently represent newly isolated
      species. The effect of 137Cs gamma-rays on the expression of the 11 mRNAs has
      been studied. Radiation inhibited the expression of the B2-like gene in the
      mutants but not in the wild-type CHO cells. The levels of the other 10 mRNAs were
      not affected by radiation. The underexpression of this group of genes in both xrs
      5 and xrs-6 mutants seems to be related to their radiation-sensitive phenotype,
      although the specific gene responsible has not been identified. Two models are
      proposed to explain the mechanism of underexpression. It is suggested that a
      cellular factor or/and chromosome structural changes are involved.

PMID- 1380657
TI  - Comparison of DNA adduct detection between two enhancement methods of the 32P
      postlabelling assay in rat lung cells.
AB  - 32P-Postlabeling analysis is a useful assay system for detecting the covalent
      binding of mutagens and/or carcinogens to DNA. The detection ability of this
      system has been tremendously enhanced by the incorporation of butanol extraction
      or nuclease P1 treatment into the experimental protocol. In this study, the
      sensitivity of adduct detection between these two enhancement methods was
      compared in vivo or in vitro with 2-aminoanthracene (2AA), 2,4,7-trinitro-9
      fluorenone (TNF), and nitrosated coal dust extract (NCDE) using the lung cells of
      rats. For the in vivo assay, male CD rats were dosed 3 times via intratracheal
      instillation, whereas for the in vitro study, rat lungs cut into small pieces
      were treated with test substances for 16 h without exogenous activation.
      Although, under the conditions tested, both the butanol and the nuclease P1
      methods detected DNA adducts caused by all 3 test agents in rat lung cells in
      vivo or in vitro, a higher adduct detecting ability was found with the butanol
      enhancement for 2AA and TNF, and with the nuclease P1 enhancement for NCDE. The
      results suggest that overall the butanol enhancement method is a more sensitive
      protocol. However, for detecting unknown adduct-forming chemicals, especially
      when they are present in complex mixtures, both enhancement methods may have to
      be used.

PMID- 1380659
TI  - 5-azacytidine induces micronuclei in and morphological transformation of Syrian
      hamster embryo fibroblasts in the absence of unscheduled DNA synthesis.
AB  - It is known that 5-azacytidine (5-AC) induces tumors in several organs of rats
      and mice. The mechanisms of these effects are still poorly understood although it
      is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA
      methylation. The known data on its clastogenic and/or gene mutation-inducing
      potential are still controversial. Therefore, we have investigated the kinds of
      genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts.
      Three different endpoints (micronucleus formation, unscheduled DNA synthesis
      (UDS) and cell transformation) were assayed under similar conditions of
      metabolism and dose at target in this cell system. 5-AC induces morphological
      transformation of SHE cells, but not UDS. Therefore, 5-AC does not seem to cause
      repairable DNA lesions. Furthermore, our studies revealed that 5-AC is a potent
      inducer of micronuclei in the SHE system. Immunocytochemical analysis revealed
      that a certain percentage of these contain kinetochores indicating that 5-AC may
      induce both clastogenic events and numerical chromosome changes.

PMID- 1380658
TI  - V(D)J recombinase-mediated deletion of the hprt gene in T-lymphocytes from adult
      humans.
AB  - The hprt T-cell cloning assay allows the detection of mutations occurring in vivo
      in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene of T
      lymphocytes. We have shown previously that the illegitimate activity of V(D)J
      recombinase accounts for about 40% of the hprt mutations in T-lymphocytes of
      human newborns as measured with umbilical cord blood samples (Fuscoe et al.,
      1991). This mechanism results in deletion of hprt exons 2 + 3. In this report, we
      examined a collection of 314 HPRT-deficient clones derived from adult humans for
      evidence that the mutations were caused by this mechanism by analyzing exons 2 +
      3 deletion mutations. DNA sequence analysis of deletion breakpoint junctions
      showed that 8 of the mutations were the result of V(D)J recombinase activity. The
      frequency of the recombinase-mediated mutations was similar in the adults and
      newborns (2-4 x 10(-7). However, since the hprt mutant frequency is about 10-fold
      higher in the adult than in the newborn, the recombinase-mediated mutations
      account for only a few percent of the adult mutations. These mutations are likely
      to have occurred during early development and persist into adulthood. Unregulated
      expression of V(D)J recombinase activity may be an important mechanism for
      genomic rearrangements in the genesis of cancer.

PMID- 1380660
TI  - Preferential induction of AT-TA transversion, but not deletions, by chlorambucil
      at the hisG428 site of Salmonella typhimurium TA102.
AB  - The chemotherapeutic agent chlorambucil effectively induces deletion mutations in
      mouse germ cells. The possibility that this chemical also effectively induces
      deletion mutations in bacterial DNA was examined using Ames Salmonella tester
      strains. Chlorambucil was mutagenic only to strains TA102 (hisG428, rfa/pKM101)
      and YG2975 (hisG46, rfa/pKM101) when S9 mix was absent. Since strain TA102 can
      detect short deletions, the mutational changes of TA102 induced by this agent
      without S9 mix were directly determined by the DNA sequencing technique. It
      turned out that chlorambucil did not induce deletion mutations but preferentially
      induced AT-TA transversions at the hisG428 site of plasmid pAQ1 of strain TA102.
      These results caution that the positive results induced by chlorambucil in
      mutagenicity tests do not necessarily mean the occurrence of deletions.

PMID- 1380661
TI  - Mutagenicity of nitro derivatives produced by exposure of dibenzofuran to
      nitrogen oxides.
AB  - Dibenzofuran (DF) was reacted with various concentrations of nitrogen oxides
      (NOx) under light irradiation. The mutagenicities of the reaction mixtures were
      tested using Salmonella typhimurium strains TA98, TA100, TA98NR and TA98/1,8-DNP6
      in the presence or absence of a mammalian metabolic activation system (S9 mix).
      DF-Nox (molar ratios 1:3, 1:6 and 1:18) reaction mixtures exhibited mutagenic
      potency in strain TA98 without S9 mix, and their direct-acting mutagenicity was
      reduced in strains TA98NR and TA98/1,8-DNP6. Four mononitrodibenzofurans and 2
      dinitrodibenzofurans, i.e., 1-nitrodibenzofuran (NDF), 2-NDF, 3-NDF, 4-NDF, 2,7
      dinitrodibenzofuran (DNDF) and 2,8-DNDF, were identified with authentic samples
      in the DF-NOx (1:18) reaction mixture by HPLC cochromatography and a gas
      chromatography/mass spectrometry study. The order of mutagenicity of
      nitrodibenzofurans in strain TA98 without S9 mix was as follows: 2,7-DNDF greater
      than 2,8-DNDF greater than 3-NDF greater than 2-NDF greater than 4-NDF greater
      than 1-NDF. The mutagenic potency of 2,7-DNDF in strains TA98 and TA100 was
      enhanced by the addition of S9 mix. Since these nitrodibenzofurans were less
      mutagenic in strains TA98NR and TA98/1,8-DNP6 than in strain TA98 without S9 mix,
      it was presumed that their mutagenicity was dependent on their activation by the
      'classical' bacterial nitroreductase and/or transacetylase, which are absent in
      strains TA98NR and TA98/1,8-DNP6 but present in strain TA98, respectively. 3-NDF
      and 4-NDF were mutagenic in strain TA100 without S9 mix. 2-NDF and 3-NDF were
      determined as corresponding amino derivatives in DF-NOx (1:3), (1:6) and (1:18)
      reaction mixtures. They contributed about 30-65% of the direct-acting
      mutagenicity of reaction mixtures in strain TA98.

PMID- 1380662
TI  - Mutagenicity of nitro-polycyclic aromatic hydrocarbons with the nitro substituent
      situated at the longest molecular axis.

PMID- 1380663
TI  - Induction of kinetochore positive and negative micronuclei in mouse bone marrow
      cells by salicylazosulfapyridine and sulfapyridine.
AB  - Salicylazosulfapyridine (SASP) and its major metabolite sulfapyridine (SP) have
      been shown to induce chromosomal damage in vivo. Both chemicals were tested in
      the micronucleus (MN)/kinetochore (KC) staining test to gain insight into the
      question of whether chromosomal breakage, aneuploidy-inducing events, or both
      were important to the observed production of MN in bone marrow cells of mice. In
      this test, both SASP and SP were shown to be strong inducers of kinetochore
      positive (KC+) MN. Although small increases in kinetochore negative (KC-) MN were
      also observed in SP treated mice, as well as in mice receiving the highest dose
      of SASP tested, the results suggest that both chemicals induce predominantly
      aneuploidogenic type damage.

PMID- 1380664
TI  - Induction of chromosomal damage in mammalian cells in vitro and in vivo by
      sulfapyridine or 5-aminosalicylic acid.
AB  - Sulfapyridine (SP) and 5-aminosalicylic acid (5-ASA) are the two primary
      metabolites of the anti-inflammatory drug salicylazosulfapyridine (SASP). These
      two metabolites were studied for induction of chromosomal damage in mammalian
      cells, in vitro and in vivo, in an attempt to understand better the genetic
      effects produced by SASP in humans and laboratory mice. To this end, SP and 5-ASA
      were tested for induction of sister-chromatid exchanges (SCE) and chromosomal
      aberrations (Abs) in Chinese hamster ovary (CHO) cells in vitro. In addition,
      they were tested in vivo for induction of micronuclei (MN) in mouse bone marrow
      polychromatic erythrocytes (PCE). SP gave positive results in the in vitro SCE
      test and the in vivo MN test, and negative results in the in vitro Abs test. 5
      ASA was negative in all three tests. These results indicate that it is the SP
      metabolite of SASP that is necessary for the induction of chromosomal damage
      reported to occur in humans and mice after treatment with SASP.

PMID- 1380665
TI  - Effect of phototherapy on sister-chromatid exchange in infants with Down
      syndrome.

PMID- 1380666
TI  - The frequencies of constitutional chromosome abnormalities in an apparently
      normal adult population.
AB  - Constitutional karyotypes were determined in 1405 apparently normal adults
      referred for population studies of acquired chromosome abnormalities in
      peripheral blood lymphocytes. A total of 7 translocations (4 reciprocal, 3
      Robertsonian), 1 extra structurally abnormal chromosome, 2 47,XXY and 12 inv(9)
      were detected. An examination of previous population studies illustrates the
      importance of considering differences in the resolution of the chromosome
      analysis when comparing frequencies of abnormalities.

PMID- 1380667
TI  - Evaluation of amitrole mutagenicity in Salmonella typhimurium using prostaglandin
      synthase activation.
AB  - Amitrole is a herbicide which has been found to induce thyroid and liver tumours
      in rodents, yet demonstrates limited genotoxic activity. The lack of mutagenicity
      of this compound in Salmonella typhimurium when employing a standard liver
      microsomal fraction, combined with evidence of activation of amitrole by
      peroxidases, warranted an investigation employing this other pathway of metabolic
      activation. Using prostaglandin H synthase as the activating system, the aromatic
      amine 2-aminofluorene provided a convenient positive control for optimisation of
      the metabolising system. Under such conditions, amitrole did not induce elevated
      numbers of revertant colonies in Salmonella typhimurium TA98, neither did it
      display evidence of interference with histidine biosynthesis as had been
      reported. Amitrole also remained nonmutagenic when preincubated at varying pHs.
      Thus, it has been shown that the alternative activation system, prostaglandin H
      synthase, does not produce metabolites which are mutagenic in the Ames test.

PMID- 1380668
TI  - Cytogenetic and molecular characterization of the mutagenicity of chlorambucil in
      V79 cells.
AB  - Chlorambucil (CBC) is used as a chemotherapeutic agent and immunosuppressant.
      Recently, it could be shown that CBC is considerably more effective than
      radiation or any chemical investigated to date in inducing high yields of germ
      line mutations that appear to be multilocus deletions or other structural
      changes. We therefore reinvestigated the in vitro genotoxic effects of CBC in V79
      cells and characterized induced sister-chromatid exchanges (SCEs), chromosome
      aberrations and gene mutations by means of cytogenetic and molecular methods. CBC
      effectively induced chromosome aberrations and SCEs in a dose-dependent manner.
      The chromosome aberrations found after a 14-h treatment were mainly chromatid
      type aberrations. 3-Aminobenzamide (3AB) did not influence the incidence of CBC
      induced SCEs and chromosome aberrations. Combined treatment with CBC and caffeine
      (CAF) strongly increased the frequency of aberrations, but had no effect on the
      yield of SCEs. CAF at lower concentrations enhanced the production of chromatid
      breaks and exchange figures while higher concentrations (10(-3) M) caused
      multiple breaks and pulverised mitoses. Mutations at the hprt locus were induced
      in a narrow range of CBC concentrations (10(-5) M-2 x 10(-5) M) and the mutagenic
      effect was accompanied by strong cytotoxicity. The CBC-induced gene mutation
      frequency was not increased after CAF treatment. The molecular analysis of CBC
      induced mutations by Southern hybridization and PCR demonstrated that CBC
      predominantly produced small alterations but not deletions or gross structural
      alterations in the hprt gene of V79 cells. For the first time, these results
      reveal striking differences in the mutagenic action of an alkylating agent in
      cultivated cells compared to germ-line cells at the molecular level.

PMID- 1380669
TI  - A straight correlation between mutagenic activity and beta-galactosidase activity
      induced by monofunctional alkylating agents.
AB  - Eight monofunctional alkylating agents were examined for their ability to induce
      mutation in Salmonella typhimurium. The assay was carried out in S. typhimurium
      TA100 with the preincubation method. The SN1-type agents were more mutagenic than
      the SN2-type ones; besides, methylating agents exerted more mutagenic activity
      than ethylating ones. Those responses in the reversion assay were quite similar
      to the results obtained previously with the beta-galactosidase assay in
      Escherichia coli CSH26/pMCP1000 (alkA'-lacZ') as to the induction of the adaptive
      response. A good correlation was found between mutagenic potency in the reverse
      mutation assay and inducing potency in the beta-galactosidase assay.

PMID- 1380670
TI  - Cystic fibrosis. Another protein out in the cold.

PMID- 1380671
TI  - Crystal structures explain functional properties of two E. coli porins.
AB  - Porins form aqueous channels that aid the diffusion of small hydrophilic
      molecules across the outer membrane of Gram-negative bacteria. The crystal
      structures of matrix porin and phosphoporin both reveal trimers of identical
      subunits, each subunit consisting of a 16-stranded anti-parallel beta-barrel
      containing a pore. A long loop inside the barrel contributes to a constriction of
      the channel where the charge distribution affects ion selectivity. The structures
      explain at the molecular level functional characteristics and their alterations
      by known mutations.

PMID- 1380672
TI  - Uncoupling of hypomyelination and glial cell death by a mutation in the
      proteolipid protein gene.
AB  - Proteolipid protein (PLP; M(r) 30,000) is a highly conserved major polytopic
      membrane protein in myelin but its cellular function remains obscure.
      Neurological mutant mice can often provide model systems for human genetic
      disorders. Mutations of the X-chromosome-linked PLP gene are lethal, identified
      first in the jimpy mouse and subsequently in patients with Pelizaeus-Merzbacher
      disease. The unexplained phenotype of these mutations includes degeneration and
      premature cell death of oligodendrocytes with associated hypomyelination. Here we
      show that a new mouse mutant rumpshaker is defined by the amino-acid substitution
      Ile-to-Thr at residue 186 in a membrane-embedded domain of PLP. Surprisingly,
      rumpshaker mice, although myelin-deficient, have normal longevity and a full
      complement of morphologically normal oligodendrocytes. Hypomyelination can thus
      be genetically separated from the PLP-dependent oligodendrocyte degeneration. We
      suggest that PLP has a vital function in glial cell development, distinct from
      its later role in myelin assembly, and that this dichotomy of action may explain
      the clinical spectrum of Pelizaeus-Merzbacher disease.

PMID- 1380673
TI  - Processing of mutant cystic fibrosis transmembrane conductance regulator is
      temperature-sensitive.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane
      Cl- channel regulated by cyclic AMP-dependent phosphorylation and by
      intracellular ATP. Mutations in CFTR cause cystic fibrosis partly through loss of
      cAMP-regulated Cl- permeability from the plasma membrane of affected epithelia.
      The most common mutation in cystic fibrosis is deletion of phenylalanine at
      residue 508 (CFTR delta F508) (ref. 10). Studies on the biosynthesis and
      localization of CFTR delta F508 indicate that the mutant protein is not processed
      correctly and, as a result, is not delivered to the plasma membrane. These
      conclusions are consistent with earlier functional studies which failed to detect
      cAMP-stimulated Cl- channels in cells expressing CFTR delta F508 (refs 16, 17).
      Chloride channel activity was detected, however, when CFTR delta F508 was
      expressed in Xenopus oocytes, Vero cells and Sf9 insect cells. Because oocytes
      and Sf9 cells are typically maintained at lower temperatures than mammalian
      cells, and because processing of nascent proteins can be sensitive to
      temperature, we tested the effect of temperature on the processing of CFTR delta
      F508. Here we show that the processing of CFTR delta F508 reverts towards that of
      wild-type as the incubation temperature is reduced. When the processing defect is
      corrected, cAMP-regulated Cl- channels appear in the plasma membrane. These
      results reconcile previous contradictory observations and suggest that the mutant
      most commonly associated with cystic fibrosis is temperature-sensitive.

PMID- 1380674
TI  - Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC
      related molecules and are heterogeneous in size.
AB  - Peptides bound to class I molecules are 8-10 amino acids long, and possess a
      binding motif representative of peptides that bind to a given class I allele. In
      the only published study of naturally processed peptides bound to class II
      molecules (mouse I-Ab and I-Eb), these peptides were longer (13-17 amino acids)
      and had heterogenous carboxy terminals but precise amino-terminal truncations.
      Here we report the characterization of acid-eluted peptides bound to HLA-DR1 by
      high-performance liquid chromatography, mass spectrometry and microsequencing
      analyses. The relative molecular masses of the peptides varied between 1,602 and
      2,996 (13-25 residues), the most abundant individual M(r) values being between
      1,700 and 1,800, corresponding to an average peptide length of 15 residues.
      Complete sequence data were obtained for twenty peptides derived from five
      epitopes, of which all but one were from self proteins. These peptides
      represented sets nested at both the N- and C-terminal ends. Binding experiments
      confirmed that all of the isolated peptides had high affinity for the groove of
      DR1. Alignment of the peptides bound to HLA-DR1 and the sequences of 35 known HLA
      DR1-binding peptides revealed a putative motif. Although peptides bound to class
      II molecules may have some related features (due to the nonpolymorphic HLA-DR
      alpha-chain), accounting for degenerate binding to different alleles, particular
      amino acids in the HLA-DR beta-chains presumably define allelic specificity of
      peptide binding.

PMID- 1380675
TI  - Protein kinase C in rat brain myelin.
AB  - It has been suggested that phosphorylation of myelin basic protein (MBP) in CNS
      is catalyzed by protein kinase C (PKC). In order to demonstrate that PKC in the
      myelin phosphorylates MBP, PKC was partially purified from rat CNS myelin by
      solubilization with Triton X-100 followed by a DEAE-cellulose column. MBP and
      histone III-S were phosphorylated in the presence of Ca2+ and phospholipid by rat
      myelin PKC. High voltage electrophoresis revealed that the phosphoamino acids in
      MBP by this kinase was serine residue, which is known to be the amino acid
      phosphorylated by PKC. The activity of PKC extracted from myelin was inhibited by
      the addition of psychosine to the incubation mixture. To confirm the presence of
      PKC molecule and to identify the isoform of PKC in the myelin, the solubilized
      myelin fraction was applied on SDS-PAGE, transferred to a nitrocellulose sheet
      and stained with anti-PKC monoclonal antibodies. Rat CNS myelin contained the PKC
      of about 80 kDa (intact PKC), and no proteolytic fragments were observed. PKC
      isozymes in myelin were type II and III. A developmental study from 14 to 42
      postnatal days showed that PKC activity in CNS myelin seemed to parallel the
      deposition of myelin protein.

PMID- 1380676
TI  - [A case of malignant glioma associated with verbal recent memory disturbance due
      to left hippocampal atrophy; case report].
AB  - Verbal recent memory disturbance was observed in a patient with a malignant
      glioma associated with left hippocampal atrophy. A 25 year-old male was admitted
      because of seizures. CT scan and MRI showed enhanced mass lesions in the left
      temporal lobe associated with ipsilateral hippocampal atrophy. Neurological
      examination disclosed right homonymous hemianopsia, word amnesia, alexia,
      agraphia and acalculia. Neuropsychological examination disclosed verbal recent
      memory disturbance, which consisted of impaired recall of the precisely memorized
      words after some interruption. Although hippocampal lesions are known to be often
      associated with cerebrovascular disease, hippocampal atrophy due to brain tumor
      is quite unusual. This case suggested that the left hippocampus is closely
      related to verbal recent memory. Hippocampal atrophy in this case conceivably
      derived from the decreased arterial flow due to perifocal edema or obstructive
      hydrocephalus.

PMID- 1380677
TI  - CCK mRNA expression, pro-CCK processing, and regulated secretion of
      immunoreactive CCK peptides by rat insulinoma (RIN 5F) and mouse pituitary tumor
      (AtT-20) cells in culture.
AB  - The rat insulinoma RIN 5F and the mouse pituitary AtT-20 cell line, which are
      known to express several biologically active peptides, were found to express CCK
      mRNA, to correctly process, and to release immunoreactive cholecystokinin (CCK)
      peptides. They expressed low levels of these peptides (about 0.4 and 0.2 ng/mg
      protein, respectively) and both cell lines processed pro-CCK to a form which co
      eluted with CCK 8 sulfate on Sephadex gel filtration chromatography and HPLC. The
      major CCK 8 immunoreactive peptide which they secreted co-eluted with CCK 8 on
      Sephadex G-50 chromatography. The secretion of CCK from both cell lines was
      significantly enhanced by treatment for 24 h with forskolin + IBMX (3-isobutyl-1
      methyl-xanthine, a phosphodiesterase inhibitor). This treatment also doubled the
      CCK content of the AtT-20 cells. It appears that the ability of different
      endocrine tumor cells to express and process CCK is not as uncommon as previously
      thought. These cells should be useful for future studies of CCK expression,
      processing, and regulation of secretion.

PMID- 1380678
TI  - Role of the cerebral ganglia in the organization of alimentary behavior of the
      pteropod mollusc Clione limacina.
AB  - The role of the cerebral ganglia in the switching of the behavior of a mollusc
      from free swimming to hunting behavior was studied. For this purpose the bodies
      of neurons providing processes to sensory and motor nerves were stained by means
      of retrograde axonal transport of Co2+ ions, and the behavioral reactions
      occurring during extracellular stimulation of particular regions of the ganglia
      were investigated. Comparison of the morphological data with the behavioral
      reactions showed that the cerebral neurons participate on the basis of sensory
      information in the switching of quiet swimming to one of three modes: hunting
      behavior (including the seizure of food), active avoidance, and passive-defensive
      behavior.

PMID- 1380679
TI  - Slow axonal transport of soluble proteins and calpain in retinal ganglion cells
      of aged rabbits.
AB  - The rate of slow axonal transport of soluble proteins in retinal ganglion cells
      of the rabbit decreased with approximately 25% in aged (6 years) compared to
      previous estimates in adult (2 years) animals. Immunobinding of calpain to
      microtiter plates coated with a monoclonal antibody to mu-calpain was used to
      isolate labelled axonally transported mu-calpain from the nerve extracts. It was
      found that the distribution of labelled mu-calpain in the retrobulbar optic
      pathway was similar to the distribution profile of the slowly migrating phase of
      soluble proteins.

PMID- 1380681
TI  - Retrograde labelling of dorsal root ganglion cells in the rat: a quantitative and
      morphological comparison of Fluoro-Gold with horseradish peroxidase labelling.
AB  - We have compared retrograde labelling of rat primary sensory neurons using Fluoro
      Gold (FG) and horseradish peroxide conjugated with wheat germ agglutinin (HRP
      WGA). Fluoro-Gold 2.5% after 48 h transit time and FG 5% after 24 and 48 h
      retrogradely labelled similar numbers of cell profiles as HRP-WGA (P greater than
      0.1% Student's t-test). The calculated cell size distribution for the above FG
      groups were similar to those for the HRP-WGA. However, FG 2.5% after a 24 h
      transit time labelled significantly fewer cells (P less than 0.001 Student's t
      test). FG retrograde transport may be used to identify the same population of DRG
      cells as HRP-WGA.

PMID- 1380680
TI  - Ontogeny of cholecystokinin receptors in the human striatum.
AB  - The distribution of cholecystokinin binding sites was studied by receptor
      autoradiography in the human striatum at midgestation, birth and adulthood. In
      the adult, cholecystokinin receptors are inhomogeneously distributed with patches
      of reduced labeling. In the caudate nucleus but not in the putamen these patches
      match the striosomal organization as revealed by acetylcholinesterase staining.
      At midgestation, patches of high density of cholecystokinin receptors are in
      register with the dopamine D1 receptor-enriched striosomes. At birth, this
      striosomal organization has already evolved into the adult pattern of higher
      matrix level in contrast to the striosomal pattern of acetylcholinesterase
      staining.

PMID- 1380682
TI  - The effects of kainate and the glutamate agonist, AMPA, are not separable in rat
      neocortical cultures.
AB  - The excitotoxic and [3H]gamma-aminobutyric acid ([3H]GABA)-releasing effects of
      quisqualate, alpha-amino-3-hydroxy-4-methyl-5-isoxazolepropionic acid (AMPA),
      kainate (KA), and their combinations were examined in primary cultures of the rat
      cerebral cortex. [3H]GABA efflux was evoked by a 5 min exposure of preloaded
      cultures to the respective agonist(s) (0.5 mM each). Cell death was induced by a
      24 h exposure of cells to 1 mM quisqualate, AMPA and/or KA, and was quantified by
      measuring lactic dehydrogenase leakage. When applied alone, each agonist induced
      remarkable [3H]GABA release and excitotoxic cell death. Simultaneous
      administration of AMPA or quisqualate and KA did not evoke stronger responses
      than KA alone. These results indicate that AMPA and KA receptors are located on
      the same cortical cells and may activate the same receptor channels and/or
      intracellular messengers.

PMID- 1380683
TI  - Nerve growth factor (NGF) receptors on mast cells: effects of the cholinergic
      neurotoxin ethylcholine mustard aziridinium ion (ECMA).
AB  - The effects of nerve growth factor (NGF) on rat peritoneal mast cells were
      studied as a model for delineating the potential actions of the cholinergic
      neurotoxin ethyl choline mustard aziridinium (ECMA) on cholinergic neuronal NGF
      receptors. Both NGF and compound 48/80 (a polycationic secretagogue) were used to
      induce histamine release from a mixed population of rat peritoneal cells in
      vitro. NGF induced a dose-dependent release of up to 80% of the total cellular
      content (160% of endogenous release) in the presence of L-alpha-phosphatidyl
      serine (10 micrograms/ml) at concentrations of 0.1-10 micrograms/ml. Compound
      40/80 also elicited comparable release of histamine over a concentration range of
      1-10 micrograms/ml. ECMA had no effect on endogenous histamine release and was
      also shown to partially block the NGF induced histamine release at a
      concentration of 6 microM and 12.5 microM, and significantly at 50 microM (50
      microM blocking up to 60% of the release). ECMA did not affect the 48/80 induced
      release. However, preincubation of the cells with ECMA (2 hr 37 degrees C)
      followed by replacement with fresh medium did not affect NGF induced histamine
      release. This suggests that although ECMA can alkylate NGF it probably does not
      inactivate the receptor in this peripheral model. Ouabain (1-10 mM) decreased
      histamine release by 25% supporting the proposed links between NGF receptor
      mediated events in neurones and the sodium pump.

PMID- 1380684
TI  - Increase in rat pup ultrasonic isolation calls induced by lindane.
AB  - The neurotoxic agent lindane was tested for its ability to alter the rate of
      ultrasonic isolation calls of suckling rats. Doses that did not produce any sign
      of convulsant activity significantly increased the number of calls and the
      cumulative time of calling in male pups. At days 10-13 of age after a single dose
      of 20 mg/kg lindane, animals showed more than twice the control call values.
      After daily dosing with 10 mg/kg during the first week of age call increases also
      appeared. It is suggested that lindane has an anxiogenic effect mediated through
      its action on the benzodiazepine-GABAA receptor-chloride channel complex.

PMID- 1380685
TI  - Effect of gamma-hexachlorocyclohexane and its isomers on proto-oncogene c-fos
      expression in brain.
AB  - By means of in situ hybridization, the induction of proto-oncogene c-fos in rat
      brain after administration of several convulsants has been studied. The
      organochlorine insecticide gamma-hexachlorocyclohexane (lindane) has been shown
      to induce c-fos expression in a dose dependent manner. 30 mg/kg of lindane
      increased c-fos expression in cortical and hippocampal areas. The two non
      convulsant isomers of lindane, alpha- and delta-HCH, were not able to induce the
      expression of the proto-oncogene, but blocked that elicited by lindane.
      Pentylenetetrazole (PTZ) and picrotoxin (PTX), a known GABAA-receptor antagonist,
      have also been considered. Both of them were able to induce c-fos, although the
      pattern of expression was not the same in each case. alpha- and delta-HCH, were
      administered prior to the mentioned toxicants, affecting the proto-oncogene
      expression in different ways. We propose here that the distribution of c-fos mRNA
      after different treatments can be used as a marker of neurotoxic action.

PMID- 1380686
TI  - Animal models for human behavioral deficiencies during development.
AB  - Often considered to be a subdiscipline of neurotoxicology, experimental
      behavioral teratology has difficulties to be acknowledged by its own right.
      Results obtained in the laboratory concerning purely behavioral effects induced
      by low level prenatal exposure to substances are often doubted to contain any
      relevance with respect to humans. This doubt is based on many debates going on in
      the numerous extrapolation steps between observed effects on animal behavior and
      human psychopathology. Taking the inverse path, extrapolation from a typical
      human behavioral syndrome (minimal brain dysfunction) to observations which can
      be made on laboratory animals, the following main debates are discussed: the
      psychology debate (behaviorism--perceptionism--cognitivism); the psychopathology
      debate (hyperactivity--attention deficit--tactile-kinesthetic perception
      deficiency--sensory integration deficits); the relevance debate (behavior is
      reprogrammable software--behavioral deficits may reflect undetectable hardware
      defects); the interpretation debate (behavioral teratogenicity is chemical
      imprinting--behavioral disturbances due to chemicals reflect neurotoxicity); the
      intelligence debate (IQ decrements--attention deficits); the developmental delay
      debate (the relevance of a delay in the behavioral development); the sensitivity
      debate (behavior is the most sensitive measure in toxicology--the brain
      redundancy and plasticity compensates subtle deficiencies); the statistics debate
      (gather as many behavioral variables as possible--stay simple and measure only
      one aspect of behavior); the regulation debate (behavioral teratology should be
      regulated in detail--tests should not be prescribed). It is attempted to find
      rational solutions for these debates which menace to jeopardize the very
      existence of behavioral teratology.

PMID- 1380687
TI  - Topographical organization of the projections from physiologically identified
      areas of the motor cortex to the striatum in the rat.
AB  - The present study was undertaken to determine in the rat the topography of the
      neostriatal projections originating from the motor cortex. For that purpose,
      anterograde tracers (Phaseolus vulgaris leucoagglutinin: PHA-L; wheat germ
      agglutinin conjugated to horseradish peroxidase: WGA-HRP) were deposited in
      discrete cortical sites physiologically identified by microstimulation. Five
      major motor areas were considered in this study: the rostral (RFL) and caudal
      (CFL) forelimb areas, the hindlimb (HL) area, the vibrissae motor-frontal eye
      field (V-FEF) region and the jaw, lips and tongue (JLT) area (according to the
      nomenclature of Neafsey et al.). The results indicate that functionally different
      regions of the motor cortex project to different sectors of the caudate putamen
      (CPU). All 3 distinct limb areas RFL, CFL and HL project to the dorsolateral
      quarter of the CPU, V-FEF area projects to the dorsomedial quarter, whereas the
      JLT area projects to the ventrolateral quarter. The pattern of terminal labeling
      is relatively consistent, whatever the cortical area in which the tracer is
      deposited. This pattern is characterized by the presence of two or more labeled
      bands which are obliquely oriented along a ventrolateral-dorsomedial axis.
      Control experiments were also undertaken in which a retrograde tracer (WGA-HRP)
      was deposited in various neostriatal loci. The results are congruent with the
      findings of the anterograde study and further indicate that a given neostriatal
      sector receives projections from cytoarchitectonically different but functionally
      related regions of the neocortex. The somatotopic features of both motor and
      somatosensory corticostriatal projections appear to be in register. In addition,
      the striatal distribution of motor cortical fibers was compared in 6 experimental
      cases to the compartmental subdivision of the striatum in patches and matrix,
      following immunohistochemical localization of calbindin 28 kDa. The calbindin
      immunoreactivity is extremely weak in the dorsolateral sector but is higher in
      the central and ventrolateral parts of the CPU. In these deep striatal regions
      receiving fibers from V-FEF, JLT and, to a lesser extent, from the limb areas,
      the cortical fibers are mostly directed to the matrix. The band-like organization
      of the projection from the motor cortex is correlated to the patch-matrix
      organization. The patches correspond to the bands of low density of terminal
      fibers and the matrix to the bands of high terminal density. The present results
      provide an anatomical basis to both electrophysiological and behavioral
      observations suggesting that functional distinctions can be established between
      subregions of the striatum.

PMID- 1380688
TI  - Oxidation of hemoglobin F is associated with the aging process of neonatal red
      blood cells.
AB  - Previously, we reported that in cord blood there is a population of very dense,
      surface area-depleted red blood cells (RBC). We hypothesized that oxidative
      damage might account for the generation of this cell population because Hb F is
      known to be mildly unstable in vitro. Accordingly, we examined density-separated
      subpopulations of neonatal red cells searching for evidence of oxidant injury to
      Hb in vivo. Cord or adult RBC were separated into populations of varying density
      and an increased amount of membrane-associated globin was found in the densest
      fraction of cord RBC. Solubilized ghosts from each fraction were analyzed by
      thiol-disulfide exchange chromatography for the presence of oxidized Hb and
      spectrophotometrically for the presence of membrane-bound hemichrome. About four
      times more oxidized Hb was found in unseparated cord RBC than in adult RBC. This
      difference was most evident in the densest 10-15% RBC subfractions. Membrane
      bound hemichrome levels in cord cells were twice those found in adult cells. We
      found that in cord membrane skeletons there was 2.5 to 9 times as much globin in
      the dense fraction as compared to the light fraction. Membrane skeletons from
      dense and light adult RBC differed little from one another. We postulate that
      membrane (and perhaps membrane skeleton)-associated oxidized Hb is a marker for
      more generalized oxidative damage, which may create the population of unusually
      dense cells found in cord blood and ultimately shorten their life span.

PMID- 1380689
TI  - Genotype/phenotype association in cystic fibrosis: analyses of the delta F508,
      R553X, and 3905insT mutations.
AB  - A striking clinical phenomenon of cystic fibrosis is the heterogeneous disease
      expression. It must therefore be assumed that the nature of the mutations
      associated with cystic fibrosis might partly determine the phenotypic
      manifestations. The relation between the cystic fibrosis mutations delta F508,
      R553X, and 3905insT and clinical parameters such as sweat test electrolytes, age
      at chronic Pseudomonas aeruginosa colonization, Chrispin-Norman x-ray scores, and
      relative underweight have been investigated in 45 patients homozygous for delta
      F508 (delta F2), in 12 compound heterozygotes for delta F508/R553X (delta
      F1/RX1), in three R553X homozygotes (RX2), and in 13 patients compound
      heterozygous for delta F508/3905insT (delta F16). We have found significant
      differences between the genetically defined subgroups concerning the mean age at
      onset and the cumulative incidence of chronic P. aeruginosa colonization and
      Chrispin-Norman x-ray scores. The significant results as well as some trends
      regarding the relative underweight demonstrate a milder clinical course in R553X
      heterozygotes and more severe disease in the delta F16 group compared to delta
      F508 homozygotes. The three patients homozygous for R553X presented with a two
      stage course showing mild progression before P. aeruginosa infection and as
      severe a course as the delta F16 patients after P. aeruginosa colonization at the
      age of 12 y. The findings presented here indicate that specific mutations can
      influence the severity and progression of the disease, implicating the importance
      of mutation and haplotype analyses. However, wide variations within the
      genetically homogeneous subgroups illustrate that other determinants of the
      clinical status do exist.

PMID- 1380690
TI  - The effects of a unique D-loop structure of a minor tRNA(UUALeu) from
      Streptomyces on its structural stability and amino acid accepting activity.
AB  - Streptomyces bldA gene, which encodes a tRNA corresponding to a very minor
      leucine codon, UUA, regulates pleiotropic gene expression which is involved in
      sporulation and secondary metabolism. The unique structural feature of this tRNA
      is the lack of GG sequence in dihydrouridine loop (D-loop) that generally is
      conserved in tRNAs involved in cytoplasmic protein biosynthesis. In order to
      investigate the relationship between the D-loop structure and the stability and
      leucine accepting activity of this tRNA, the wild and D-loop mutant tRNA
      transcripts were constructed with T7 RNA polymerase in vitro. The wild type
      tRNA(UUALeu) showed the structural stability and leucine accepting activity at
      physiological temperature for Streptomyces. The E.coli type D-loop mutant, which
      has a larger loop size and contains a GG doublet, exhibited increased
      thermostability. The kinetical analyses of the aminoacylation reaction of
      tRNA(UUALeu) with S.lividans and E.coli leucyl-tRNA synthetase (LeuRS) suggest
      there is a unique recognition mechanism of Streptomyces LeuRS toward
      tRNA(UUALeu).

PMID- 1380691
TI  - Foret1, a reverse transcriptase-like sequence in the filamentous fungus Fusarium
      oxysporum.
AB  - We report here the isolation of Foret1, a repeated DNA sequence cloned from the
      fungal plant pathogen Fusarium oxysporum. This clone exhibits a high degree of
      sequence similarity with the retroviral pol genes. Sequences homologous to
      protease, reverse transcriptase, ribonuclease H are found in that order. The
      overall structure is homologous to the 'gypsy' class of LTR-retrotransposons. Its
      similarity to elements present in widely different organisms may result from its
      horizontal transmission in recent evolutionary time.

PMID- 1380692
TI  - The mechanism of trans-activation of the Escherichia coli operon thrU(tufB) by
      the protein FIS. A model.
AB  - Transcription of the thrU(tufB) operon is trans-activated by the protein FIS
      which binds to the promoter upstream activator sequence (UAS). Deletions of parts
      of the UAS and insertions show that optimal trans-activation requires occupation
      by FIS of the two FIS-binding regions on the UAS and specific helical positioning
      of these regions. On the basis of these and other data, a model for the mechanism
      of thrU(tufB) trans-activation by FIS is proposed. This model implies that the
      mechanisms underlying stimulation by FIS of two totally different processes:
      inversion of viral DNA segments and transcription of stable RNA operons, are
      essentially the same.

PMID- 1380693
TI  - Nucleotide sequence of tRNA(Thr1) of Escherichia coli and of the gene (thrV) that
      encodes it.

PMID- 1380695
TI  - Rapid characterisation of differentially expressed members of multigene families.

PMID- 1380694
TI  - The human gene for apurinic/apyrimidinic endonuclease (HAP1): sequence and
      localization to chromosome 14 band q12.

PMID- 1380696
TI  - Bleomycin mediated degradation of DNA-RNA hybrids does not involve C-1'
      chemistry.
AB  - Incubation of Fe(II) bleomycin and O2 with a number of 'A'-like DNA-RNA hybrid
      homopolymers at 4 atm O2 results in formation of base propenal and base in a
      ratio of approximately 1.0:1.0. This ratio differs dramatically from the
      corresponding ratio of approximately 10:1.0 observed when activated BLM degrades
      'B'-like DNA homopolymers. Experiments were undertaken to determine if the shift
      to enhanced base production observed in the A-like hybrids is the result of C-1'
      chemistry in addition to the C-4' chemistry normally observed with B-like DNA
      under identical conditions. Increased accessibility of the 1'-hydrogen might be
      anticipated due to widening of the minor groove in the A-like conformers.
      Experiments using poly([1'-3H]dA) poly(rU) and poly([U-14C]dA) poly(rU) indicated
      that neither 3H2O nor deoxyribonolactone accompanied adenine release. In
      addition, studies using poly([4'-2H]dA) poly(rU) and poly([1'-2H]dA) poly(rU)
      unambiguously establish that the altered base to base propenal ratio is not the
      result of C-1' chemistry, but a direct consequence of C-4' chemistry.

PMID- 1380697
TI  - A ribosomal ambiguity mutation in the 530 loop of E. coli 16S rRNA.
AB  - A series of base substitution and deletion mutations were constructed in the
      highly conserved 530 stem and loop region of E. coli 16S rRNA involved in binding
      of tRNA to the ribosomal A site. Base substitution and deletion of G517 produced
      significant effects on cell growth rate and translational fidelity, permitting
      readthrough of UGA, UAG and UAA stop codons as well as stimulating +1 and -1
      frameshifting in vivo. By contrast, mutations at position 534 had little or no
      effect on growth rate or translational fidelity. The results demonstrate the
      importance of G517 in maintaining translational fidelity but do not support a
      base pairing interaction between G517 and U534.

PMID- 1380698
TI  - RNA-DNA hybridization promoted by E. coli RecA protein.
AB  - RecA protein of E. coli plays a central regulatory role that is induced by damage
      to DNA and results in the inactivation of LexA repressor. In vitro, RecA protein
      binds preferentially to single-stranded DNA to form a nucleoprotein filament that
      can recognize homology in naked duplex DNA and promote extensive strand exchange.
      Although RecA protein shows little tendency at neutral pH to bind to RNA, we
      found that it nonetheless catalyzed at 37 degrees C the hybridization of
      complementary RNA and single-stranded DNA sequences. Hybrids made by RecA protein
      at 37 degrees C appeared indistinguishable from ones prepared by thermal
      annealing. RNA-DNA hybridization by RecA protein at neutral pH required, as does
      RecA-promoted homologous pairing, optimal conditions for the formation of RecA
      nucleoprotein filaments. The cosedimentation of RNA with those filaments further
      paralleled observations made on the formation of networks of nucleoprotein
      filaments with double-stranded DNA, an instrumental intermediate in homologous
      pairing in vitro. These similarities with the pairing reaction support the view
      that RecA protein acts specifically in the hybridization reaction.

PMID- 1380699
TI  - Regioselective ligation of oligoribonucleotides using DNA splints.

PMID- 1380700
TI  - Phenol as grinding material in RNA preparations.

PMID- 1380701
TI  - [Biosynthesis of substance P and other mammalian neurokinins].

PMID- 1380702
TI  - [Neurokinin receptors. The role of substance P in inflammatory processes].

PMID- 1380703
TI  - Effects of nitric oxide synthase inhibitors on the relaxation induced by non
      adrenergic non-cholinergic nerve-stimulation in the rat gastric fundus.

PMID- 1380704
TI  - Ischemia-reperfusion injury and histamine release in isolated perfused guinea-pig
      heart: effects of nitric oxide generators.

PMID- 1380705
TI  - Peripheral cardiovascular effects of tachykinins in conscious freely moving
      spontaneously hypertensive and Wistar Kyoto rats.

PMID- 1380706
TI  - Thermic and UV instability of hetastarch.

PMID- 1380707
TI  - Effects of indomethacin and diclofenac on substance P induced chemotaxis of human
      monocytes and polymorphonuclear cells.

PMID- 1380708
TI  - Domoic acid toxicity in rats and mice after intracerebroventricular
      administration: comparison with excitatory amino acid agonists.
AB  - A behavioural study of the domoic acid (DOM)-induced convulsive behaviour after
      intracerebroventricular administration was carried out in rats and mice. DOM
      induced behaviours were compared to those elicited by other excitatory amino acid
      (EAA) agonists N-methyl-D-aspartate (NMDA), alpha-amino-3- hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) and kainic acid (KA), in such a way as to assess
      the possible similarities between DOM-induced effects and EAA subtype receptor
      activation in vivo. In rat, DOM (0.03-3 nmol/rat) caused a complex pattern of
      convulsive behaviour, quantified by means of a 15-point rating scale. DOM-induced
      behavioural profile was characterized at the lower doses by "preconvulsive"
      behaviours as wet dog shakes, hypermotility, mild facial clonus. At higher doses,
      DOM caused clonic convulsions followed by the "status epilepticus" syndrome (wet
      dog shakes, forelimb clonus, rearing, salivation). Rats treated with KA (0.3-10
      nmol/rat) showed an almost identical behavioural profile. AMPA (1-10 nmol/rat)
      induced convulsive behaviour was similar to DOM and KA only at the higher doses.
      NMDA (0.25-10 nmol/rat) caused clonic convulsions but not "status epilepticus".
      In mice, similar results were obtained: all the tested drugs induced generalized
      seizures, but only animals treated with DOM, KA and AMPA showed a prolonged
      sequence of seizures with forelimb clonus. Our results confirm the findings
      reported in the literature and support the hypothesis that DOM and KA act at the
      same EAA receptor.

PMID- 1380709
TI  - Comparison of the effects of thapsigargin and BAY K 8644 on spontaneous
      mechanical activity in rat portal vein and contractile responses of rat cardiac
      muscle.
AB  - The effect of thapsigargin, 10(-9)-10(-6) M, and Bay K 8644, 10(-9)-10(-7) M, was
      studied on isolated portal veins and cardiac muscles from rats. In rat portal
      veins thapsigargin induced a concentration dependent increase in the amplitude of
      the spontaneous mechanical activity without increasing the frequency of
      spontaneous activity. Thapsigargin was less effective than Bay K 8644 in
      increasing the amplitude of the mechanical activity. In contrast to thapsigargin
      Bay K 8644, 10(-6) M increases the frequency of the mechanical activity.
      Atropine, 10(-6) M, and phentolamine, 10(-6) M, had no effect on the thapsigargin
      and Bay K 8644 induced increase in mechanical activity. Nitrendipine, 10(-6) M,
      totally abolished the mechanical response in preparations stimulated by
      thapsigargin and Bay K 8644. In rat atrial and papillary muscles Bay K 8644
      increases the frequency in right atrium and tension in both atrial and papillary
      muscles. Thapsigargin was without effect on the frequency and tension in the
      cardial preparations. In conclusion, thapsigargin increases the amplitude of
      spontaneous activity in rat portal veins. In contrast to Bay K 8644 thapsigargin
      was less effective in increasing the amplitude and had no effect on the frequency
      of spontaneous activity; furthermore, thapsigargin was without effect on cardiac
      muscles. The results support the view that an endoplasmatic Ca2(+)-pump sensitive
      to thapsigargin is of importance for spontaneous activity in portal veins while
      such pump is of minor importance for contractile activity in cardiac muscles.

PMID- 1380710
TI  - GTP-binding proteins and post-receptor components in hypertension.
AB  - Alterations in neurohormonal response are a widely-observed feature in various
      forms of hypertension. Such responses depend not only on levels of
      hormones/neurotransmitters, but also on receptors and post-receptor components.
      With respect to G protein-coupled receptors, such as those for catecholamines,
      angiotensin II, and bradykinin, it is possible that G-proteins or G protein
      coupled effector molecules are altered in hypertension. In this article, several
      classes of G alpha proteins and effectors which link to these proteins are
      briefly discussed. Evidence is presented in support of the concept that signal
      amplification in G protein-coupled receptor systems occurs at the level of
      receptor activation of the G proteins. Limited data are as yet available that
      directly assess whether changes in the amount or properties of particular G alpha
      proteins or G-protein-linked effectors, are altered in hypertension. The
      availability of antibody, cDNA and other genetic probes should prove highly
      useful in testing the hypothesis that such alterations are important for the
      pathogenesis and maintenance of the hypertensive state.

PMID- 1380711
TI  - hCG, AFP, and uE3 patterns in the 14-20th weeks of Down's syndrome pregnancies.

PMID- 1380712
TI  - [Spindle cell carcinoma of the pancreas: a case report with immunohistologic
      study].

PMID- 1380714
TI  - Correlation of magnetic resonance image and histology of human teeth.
AB  - Current methods for diagnosis of pulpal pathosis are often inadequate and there
      is a need for an in vivo method to visualize dental pulp tissue. This report
      compares micromagnetic resonance imaging (MMRI) with routine H & E histology on a
      cross sectional view of a molar tooth. The extracted tooth was imaged with a
      Bruker AM-400 NMR spectrometer modified with a microimaging accessory. The tooth
      was then decalcified and sectioned at the same level as the MMR image. Image
      intensity readings were acquired for specific areas of the pulp chamber for
      comparison with histology. The results demonstrate that there is a close
      correlation between the MMRI and the low power H & E appearance of pulp tissue.

PMID- 1380713
TI  - Effects of dental trauma on pulpal and periodontal nerve morphology.
AB  - Regeneration and morphological changes in sensory peptidergic nerves in pulp and
      periodontium were studied after general dental trauma by means of
      immunohistochemistry. In control teeth also the total nerve supply was
      demonstrated by using antibody to the general neuronal marker, protein gene
      product (PGP)9.5. Two experimental rat models were used, i.e. tooth replantation
      and induced traumatic occlusion. Results from these studies are reviewed here. In
      the controls, the PGP9.5-immunoreactive(IR) nerve supply in pulp and periodontium
      was generally denser compared to CGRP-IR and SP-IR nerves. In the replanted
      teeth, regeneration of CGRP-IR nerves closely followed the pulp cell renewal.
      Density and distribution of the regenerated nerves showed two different patterns
      which seemed to depend on the capacity of the renewed pulp to form postoperative
      dentine. The nerve density never reached the same level as the controls. In teeth
      not able to form irregular dentine, the pulp was sparsely innervated and the pulp
      cavity was filled with innervated bone. Nerve responses in CGRP-IR and SP-IR
      nerves after unilateral induced traumatic occlusion in the first maxillary molar
      were studied at different observation periods up to 30 days. After 5 days,
      localized morphological nerve changes were found both in the pulp and
      periodontium within the total rat molar dentition. With increasing observation
      periods, the pulpal neural changes progressed and were extended to all pulpal
      areas compared to the periodontium, where the nerve responses remained localized
      to cervical and apical tissues throughout the experiment.

PMID- 1380715
TI  - Effect of substance P administration on vascular permeability in the rat dental
      pulp and submandibular gland.
AB  - The effects of substance P (SP) administration on vascular permeability were
      studied in the dental pulp (DP) of upper and lower incisors and in the
      submandibular gland (SMG) of male rats. Vascular permeability was assessed by
      means of extravasation of Evans blue dye. SP was diluted in 0.5% bovine serum
      albumin (BSE) and infused into the left common carotid artery. Separate groups of
      animals receive chloropyramine, an H1 histamine receptor antagonist (10 mg kg-1
      i.v.) or indomethacin, a prostaglandin synthesis inhibitor (4 mg kg-1 i.v.) prior
      to SP infusions. Infusion of SP for 5 min increased plasma extravasation both in
      DP and SMG, with a threshold of about 30 pmol min-1 and 74 pmol min-1,
      respectively. Enhanced salivary secretion was also observed. Although the
      administration of 74 pmol min-1 of SP significantly lowered the systemic blood
      pressure, experimental hypotension elicited by haemorrhage did not influence
      vascular permeability in either organ tested. After chloropyramine administration
      the SP effect on vascular permeability in both DP and SMG was abolished.
      Indomethacin pretreatment failed to prevent the permeability-enhancing action of
      SP. Our results suggest that substance P increases both pulpal and glandular
      plasma extravasation in the rat indirectly, via the release of histamine and the
      activation of H1 histamine receptors.

PMID- 1380716
TI  - Vascularization after pulpotomy.
AB  - The vascular changes of the pulpal vessels in experimentally induced pulpotomy in
      dog tooth were investigated using microcorrosive resin casts technique and
      scanning electron microscopic examination. The pulpal tissues of the permanent
      mandibular molars were amputated and then dressed with calcium hydrate. At one to
      eight weeks after pulpotomy, the experimental teeth were prepared for resin casts
      of pulpal vessels with hard tissues. One week after pulpotomy, a concave region,
      which was supposed to be due to the compression by the calcium hydrate, was found
      in the newly formed pulpal vascular network. Around the concave region was a
      flat, dense capillary network. In eight weeks, the thick dentin bridge was formed
      in close proximity to the amputated pulpal surface. The vascular network just
      beneath the dentin bridge changed into similar features in the three layers of
      the normal pulpal vascular architecture, which are (i) terminal capillary network
      (TCN), (ii) capillary network (CN), and (iii) venular network (VN) and which
      distributed in the superficial layer of the pulpal vessels.

PMID- 1380717
TI  - Jamaican studies in nutrition and child development, and their implications for
      national development.

PMID- 1380718
TI  - Neurochemical and motor effects of high dose haloperidol treatment: exacerbation
      by tryptophan supplementation.
AB  - The neurochemical and motor effects of a high dose (25 mg/kg) of haloperidol were
      assessed in male Sprague-Dawley rats. In Experiment 1, this high dose of
      haloperidol caused dramatic increases in striatal dopaminergic and serotonergic
      turnover that only returned to control levels 100 hr after injection. In the
      second experiment, the same dose of haloperidol was administered twice over a 3
      week interval in the presence or absence of a dietary tryptophan supplement added
      to the drinking water. Rats were assessed for disruption of locomotor behavior
      (using the rotorod) as well as the occurrence of spontaneous (dyskinetic-like)
      chewing and head twitching. It was observed that haloperidol impaired rotorod
      performance in a manner that paralleled the time course of the neurochemical
      changes in Experiment 1. In addition, the tryptophan (consumed at an average of
      157 mg/kg/day) exacerbated the deficit in rotorod performance in haloperidol
      treated rats after the first, but not after the second, haloperidol injection.
      Finally, the combination of haloperidol plus tryptophan was found to cause a long
      lasting increase in spontaneous chewing movements that lasted 56 days after the
      first injection. These observations are interpreted in the context of tryptophan
      supplementation to antipsychotic therapy.

PMID- 1380720
TI  - FK 506 reduces the injury experienced following renal ischemia and reperfusion.
AB  - The effect of FK 506 pretreatment on renal ischemia and reperfusion (I/R) injury
      was investigated. Adult male rats were assigned to one of two groups (20 animals
      each). Group 1 (controls) received 0.5 mL saline while group 2 received FK 506
      (0.3 mg/kg) intravenously 24 h prior to the induction of renal ischemia. After a
      60-min period of ischemia of the right kidney, a left nephrectomy was performed.
      Blood for BUN, creatinine, and tumor necrosis factor (TNF) was obtained prior to
      ischemia and on days 1, 2, 3, 5, 7, and 10. All surviving animals were sacrificed
      at day 10. FK 506 pretreatment reduced the serum levels of BUN (p less than .02),
      creatinine (p less than .02) and TNF (p less than .05) as compared to that seen
      in controls. Based upon these data, it appears that: (a) renal ischemia induces
      the release of TNF; (b) FK 506 pretreatment inhibits TNF production; and (c) FK
      506 reduces renal injury association with I/R.

PMID- 1380719
TI  - Stabilities of double- and triple-strand helical nucleic acids.
AB  - In this selected literature survey, we have seen that the stabilities of duplexes
      and triplexes are governed by the vertical base stacking, the horizontal specific
      base-paired H-bonding and the environmental parameters. The entropic contribution
      in the solvation/desolvation process is important in driving the aggregation of
      NA strands and duplex formation, but base stacking and specific H-bonding
      maintain the helical order. Triplex formation shares most of the physical
      environmental prerequisites with those of duplex NAs. However, some additional
      environmental conditions are often needed. Only in low pH solution is the
      polycytidylic strand protonated and, thus, it is possible for the strand to bind
      to a G.C duplex sequence to give the C+(G.C) triplex. High ionic strength is
      often necessary for the screening of inter-phosphate repulsion due to the high
      linear charge density in triplexes. The presence of specific counterions is
      important for complexation. In the absence of negative supercoiling, existence of
      an intramolecular triplex is rare except under very acidic conditions for the
      formation of C+(G.C)-type intramolecular triplex. As expected, the stabilities of
      both inter- and intramolecular triplexes increase with sequence length. The
      thermodynamic principles of helix-coil transition of oligo-duplex may be
      described by the van't Hoff relationship, which assumes a two-state cooperative
      melting profile. Thus, the enthalpy, entropy and free energy of transition can be
      evaluated from the experimental melting curves (e.g. OD, DSC). For
      polynucleotides, because of the non-two-state nature of transition, the simple
      van't Hoff relationship is no longer valid, and direct calorimetry is needed to
      obtain reliable thermodynamic parameters. The pH and salt concentration
      dependence of duplex stability can be formulated and derived from a van't Hoff
      equation. Base-stacking patterns are simple in duplexes but not so in triplexes
      due to the diversity in triplet schemes. The sequence dependence of base stacking
      for duplexes has been characterized and employed to predict the stability of an
      arbitrary sequence. In conclusion, the stability of duplex is relatively well
      characterized by thermodynamic data in terms of both base stacking and specific H
      bonding. Thermodynamic studies of triplexes have been far fewer in number.
      Oligonucleotides have found application in the detection and localization of a
      mRNA or its gene, the detection of bacterial or viral sequences, and the
      inhibition of the translation of mRNA and the transcription and replication of
      DNA (Englisch and Gauss, 1991). In a different approach, oligonucleotides have
      been targeted directly to a DNA duplex motif of a gene in order to inhibit the
      expression at the beginning of the transcriptional process.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1380721
TI  - Protective effects of diltiazem and the prostazycline analogue iloprost in human
      renal transplantation.
AB  - To test the hypothesis that calcium antagonists decrease the incidence and
      severity of delayed graft function, we conducted three separate, prospective,
      randomized trials. In these trials, we investigated the effects of diltiazem and
      those of the prostacycline analogue iloprost. In the first study, 22 control
      patients and 20 diltiazem patients received grafts perfused with either vehicle
      or diltiazem 20 mg/L in the Euro-Collins solution. Subsequently, the diltiazem
      subjects were given the drug as a bolus of 0.28 mg/kg, followed by a continuous
      infusion of 0.002 mg/min/kg for the following 2 days. Thereafter, diltiazem 60 mg
      was given to the treated subjects orally for up to 4 years. In the second study,
      11 control subjects and 10 diltiazem subjects received the same postoperative
      regimen, but all grafts were harvested without addition of diltiazem to the
      perfusion solution. In the third protocol, four groups were studied as follows:
      19 control subjects who received no specific treatment, 16 subjects who received
      diltiazem, 16 subjects who were given iloprost, and 14 subjects who received both
      iliprost and diltiazem. The donor kidney of treated patients was perfused with
      either diltiazem, iloprost, or both drugs. Primary graft function occurred more
      commonly in the groups receiving diltiazem. Further, in the first study the
      number of hemodialyses per patient was reduced in those patients with delayed
      graft function. Fewer rejection episodes occurred in patients receiving
      diltiazem. Plasma levels of soluble interleukin-2 receptors decreased
      significantly during diltiazem treatment. Moreover, renal biopsies showed less
      severe signs of cyclosporin-A (CyA) nephrotoxicity in diltiazem-treated patients
      compared to controls, even though these patients also exhibited higher CyA trough
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380722
TI  - IgE-mediated reaction to vancomycin and teicoplanin after treatment with
      vancomycin.
AB  - A 38-year-old male patient developed severe signs of type 1 allergy after
      treatment with vancomycin. By the basophil histamine release test, the patient's
      isolated basophil leucocytes were shown to react IgE dependent after challenge
      with vancomycin and teicoplanin. This indicates that the patient is type 1
      allergic towards vancomycin and teicoplanin.

PMID- 1380723
TI  - An animal model for cystic fibrosis made by gene targeting.
AB  - Cystic fibrosis results from defects in the gene encoding a cyclic adenosine
      monophosphate-dependent chloride ion channel known as the cystic fibrosis
      transmembrane conductance regulator (CFTR). To create an animal model for cystic
      fibrosis, mice were generated from embryonic stem cells in which the CFTR gene
      was disrupted by gene targeting. Mice homozygous for the disrupted gene display
      many features common to young human cystic fibrosis patients, including failure
      to thrive, meconium ileus, alteration of mucous and serous glands, and
      obstruction of glandlike structures with inspissated eosinophilic material. Death
      resulting from intestinal obstruction usually occurs before 40 days of age.

PMID- 1380724
TI  - Defective epithelial chloride transport in a gene-targeted mouse model of cystic
      fibrosis.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an
      adenosine 3',5'-monophosphate (cyclic AMP)-activated chloride channel. In cystic
      fibrosis (CF) patients, loss of CFTR function because of a genetic mutation
      results in defective cyclic AMP-mediated chloride secretion across epithelia.
      Because of their potential role as an animal model for CF, mice with targeted
      disruption of the murine CFTR gene [CFTR(-/-)] were tested for abnormalities in
      epithelial chloride transport. In both freshly excised tissue from the intestine
      and in cultured epithelia from the proximal airways, the cyclic AMP-activated
      chloride secretory response was absent in CFTR(-/-) mice as compared to
      littermate controls. Thus, disruption of the murine CFTR gene results in the
      chloride transport abnormalities predicted from studies of human CF epithelia.

PMID- 1380725
TI  - Mutations in the rod domains of keratins 1 and 10 in epidermolytic
      hyperkeratosis.
AB  - Epidermolytic hyperkeratosis is a hereditary skin disorder characterized by
      blistering and a marked thickening of the stratum corneum. In one family,
      affected individuals exhibited a mutation in the highly conserved carboxyl
      terminal of the rod domain of keratin 1. In two other families, affected
      individuals had mutations in the highly conserved amino terminal of the rod
      domain of keratin 10. Structural analysis of these mutations predicts that
      heterodimer formation would be unaffected, although filament assembly and
      elongation would be severely compromised. These data imply that an intact keratin
      intermediate filament network is required for the maintenance of both cellular
      and tissue integrity.

PMID- 1380726
TI  - Immunodominant T cell epitope from signal sequence.

PMID- 1380727
TI  - [Interpretation of experimental data in the presence of accidental perturbations:
      characterization of the bladder].
AB  - Some tests are subject to the influence of a special kind of "irreducible"
      effects which do not satisfy the Central Limit Theorem of statistics, even though
      they show no systematic character or tendency. These effects especially present
      when physiological experiments are concerned "in vivo". In such the lack of
      specific methods to reduce these effects brings about the necessity of special
      case in minimizing the loss of information. Contained in the experimental data as
      well as the accumulation of useless information. Recent work has suggested the
      extensive use of several indexes derived from combination of available variables
      and their respective mathematic correlation. The information obtained by
      following this methodology has the character of "working hypothesis" so it needs
      many favorable confirmation to assess its reliability. It is convenient to
      analyze a large number of relations in order to emphasize the concordant effects
      and discord the others. In order to obtain some preliminary indication of the
      reliability of this procedure we have analyzed some CMG curves in prostatic and
      non-prostatic subject. The final slope of the curves (urge point) t = dP/dVr has
      been adapted as an index of the "elasticity" of the bladder; it was compared with
      the filling volume, the muscular volume and their ratio, i.e. with a geometric
      index of the bladder shape. The correlation show that the index t can, to some
      extent significantly represent the mechanical behaviour of the bladder in its
      physiological condition or when there is a partial obstruction of urine
      deflection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380728
TI  - Basic biology of the hematopoietic growth factors.

PMID- 1380729
TI  - Granulocyte colony-stimulating factor (G-CSF): preclinical and clinical studies.

PMID- 1380730
TI  - Hematopoietic growth factors in AIDS.
AB  - Three hematopoietic growth factors, erythropoietin, GM-CSF, and G-CSF, have all
      been evaluated in the context of HIV infection. Recombinant human Epo is
      currently licensed for therapy of anemia related to zidovudine and is well
      tolerated in this patient population. Although myelosuppression can clearly be
      overcome using recombinant human GM-CSF or G-CSF in HIV-infected hosts, the
      clinical benefits for such patients are still not determined. It is likely that
      these growth factor therapies will allow for delivery of certain important
      myelosuppressive medications that otherwise could not be tolerated. Improvements
      in virological quantitation in vivo should help settle the controversies
      regarding modulation of HIV replication caused by cytokine treatment. The
      clinical use of hematopoietic growth factors in HIV disease requires further
      study with regard to the optimization of increases in blood cell number and/or
      modulation of blood cell function.

PMID- 1380731
TI  - The role of colony-stimulating factors in infectious disease: current status,
      future challenges.

PMID- 1380732
TI  - In vivo biology and therapeutic potential of hematopoietic growth factors and
      circulating progenitor cells.

PMID- 1380733
TI  - Regulatory issues involved in hematopoietic growth factor approval.

PMID- 1380735
TI  - Concomitant radiotherapy and chemotherapy for anal cancer.
AB  - Concomitant radiotherapy/chemotherapy is widely used to treat epidermoid cancers
      of the anal canal. The drugs most frequently combined with radiotherapy are 5
      fluorouracil and mitomycin, but other schedules include 5-fluorouracil and
      cisplatin, 5-fluorouracil alone, or bleomycin alone. Since mechanisms of possible
      interaction between radiotherapy and the cytotoxic drugs are not well understood,
      schedules have been developed empirically. Randomized trials comparing
      radiotherapy/chemotherapy with radical radiotherapy alone have not yet been
      completed. In nonrandomized studies, however, some drug and radiotherapy
      combinations appear to be superior to radiotherapy alone. Combined modality
      therapy has resulted in 5-year survival rates of 65% to 80%; approximately 85% of
      patients retain anorectal function when the primary tumor is controlled by
      concomitant radiotherapy/chemotherapy.

PMID- 1380734
TI  - Future of basic/clinical hematopoiesis research in the era of hematopoietic
      growth factor availability.

PMID- 1380736
TI  - Recent advances in the treatment of chronic lymphocytic leukemia: defining the
      role of intravenous immunoglobulin.

PMID- 1380737
TI  - The role of hematopoietic growth factors in the treatment of neoplastic diseases.

PMID- 1380738
TI  - From illness to symbol and symbol to illness.
AB  - This paper explores two aspects of the relationship between illness and social
      symbols: one in which illnesses become symbols; the other, in which symbols
      become implicated in processes that eventuate in illness. Illness is first
      discussed as a symbol of social beliefs, attitudes, norms, values, and other
      social phenomena conceptualized in relation to them. This symbolization is
      analyzed as it relates to various dimensions of illness that lend themselves to
      figurative thinking. The paper then turns to processes through which social
      symbols may generate illness. In this regard, ways in which social symbols may
      attract people to behavior that puts their health at risk are discussed. The
      paper concludes with an analysis of how the development of illness may be
      affected by the relationship between social symbols and somatization.

PMID- 1380739
TI  - Three distinct candidate point mutations of the von Willebrand factor gene in
      four patients with type IIA von Willebrand disease.
AB  - Type IIA von Willebrand disease (vWD) is the most common type II vWD and is
      characterized by the selective loss of large and intermediate sized multimers.
      One explanation for this disorder has been postulated to be a qualitative defect
      in von Willebrand factor (vWF) which results in increased susceptibility to
      proteolysis at the bond between residues Tyr842 and Met843. Four missense
      mutations that may cause type IIA vWD have recently been identified near the
      cleavage site. We analyzed the molecular basis for type IIA vWD in six patients.
      A 512 bp DNA sequence spanning the proteolytic cleavage site was targeted for PCR
      amplification and sequencing. We exploited a difference in restriction sites
      between the vWF gene and the pseudogene and have designed allele-specific
      oligomer used with PCR to distinguish these two genes. Three candidate missense
      mutations; Ser743 (TCG)----Leu (TTG), Leu799 (CTG)----Pro (CCG), and Arg834 (CGG)
      ---Trp (TGG) were identified in 4 out of 6 patients. The amino acid substitution
      at Arg834 has been reported previously, but the other substitutions at Ser743 and
      Leu799 are novel candidate mutations locating 99 and 43 amino acids to the N
      terminal side of the cleavage site, respectively. Our results indicate that amino
      acid substitutions located relatively distant from the cleavage site may also be
      involved in type IIA vWD.

PMID- 1380740
TI  - Monoclonal antibodies to toxin II from the scorpion Androctonus australis Hector:
      further characterization of epitope specificities and neutralizing capacities.
AB  - The epitope specificities of two previously prepared monoclonal antibodies (mAb)
      to the toxin II from Androctonus australis Hector were characterized. Neither mAb
      4C1 nor mAb 3C5 was able to recognize any of the 58 overlapping synthetic
      heptapeptides which cover the whole sequence of toxin II. Thus, both mAbs
      probably recognize conformation-dependent epitopes at the surface of the toxin.
      Experiments were designed to check whether or not the two mAbs, or their Fab
      fragments, were able to bind simultaneously to the toxin. The results indicated
      that the epitopes recognized by the two antibodies are probably close together at
      the surface of the toxin, thus preventing the simultaneous binding of both mAbs
      to a single toxin molecule. Given the proximity of the two epitopes and the fact
      that mAb 4C1 is known to be a neutralizing antibody, the capacity of mAb 3C5 to
      inhibit the toxic effects of the toxin was re-evaluated in C57BL/6 mice. A clear,
      but weak, neutralizing effect was found, consistent with the low affinity binding
      of the mAb in the proximity of a neutralizing site of the toxin.

PMID- 1380741
TI  - Nonpeptide antagonists herald new era in tachykinin research.

PMID- 1380742
TI  - Glutamate receptor channels: novel properties and new clones.
AB  - Glutamate is the principal excitatory neurotransmitter in the brain. Glutamate
      activates cation-selective receptor channels carried by nearly every neuron and
      by glial cells. Bernd Sommer and Peter Seeburg describe how our concepts
      concerning the molecular and functional design of ionotropic glutamate receptors
      are rapidly progressing, with the recent discovery of novel receptor properties
      and new subunits following the landmark cloning of the first receptor subunit by
      M. Hollmann and his colleagues. New properties currently revealed by the cloned
      receptor channels may guide physiologists in characterizing the elementary steps
      in synaptic transmission, help neurologists to define the role of glutamate
      receptors in acute and chronic neuropathologies, and enlighten all
      neuroscientists whose models for learning and memory involve the idiosyncracies
      of particular channel subtypes.

PMID- 1380743
TI  - [Beta-HCG-producing ovarian dysgerminoma].
AB  - A patient with stage 2C pure dysgerminoma which produced free beta-HCG subunit is
      described. The importance of excluding elements of other germ cell tumors is
      stressed. HCG-positive dysgerminomas should be treated like other pure
      dysgerminomas, and beta-HCG will in this case be a useful monitor of the effect
      of treatment.

PMID- 1380744
TI  - [Palliative treatment of rectal and sigmoid cancer with Nd-YAG laser].
AB  - Nd-YAG laser treatment was employed as palliative treatment in 47 patients with
      colorectal cancer. Thirty-eight patients (81%) experienced good symptomatic
      effect from the treatment. Four complications occurred: three cases of
      perforation and one case of moderate bleeding. There was no mortality. It is
      concluded that laser treatment is a good palliative method in patients with
      colorectal cancer, especially in elderly patients with complicating diseases and
      in patients with local recurrence or symptoms from nonresected tumours.

PMID- 1380745
TI  - The effect of acute distension on vasoactive intestinal polypeptide (VIP),
      neuropeptide Y (NPY) and substance P (SP) immunoreactive nerves in the female rat
      urinary bladder.
AB  - The effect of acute distension on vasoactive polypeptide (VIP)-, neuropeptide Y
      (NPY)- and substance P (SP)-immunoreactive nerves in the wall of the urinary
      bladder was investigated. At the age of 3 months, 25 female albino rats underwent
      forced diuresis combined with balloon obstruction to achieve maximal distension
      for 3 h. A modified, indirect immunofluorescence detection method was applied 2
      days, 7 days and 21 days after distension. A marked, extensive depletion of VIP,
      NPY- and SP-immunoreactive nerves was observed after distension. This disturbance
      was reversible, and increased fluorescence of VIP-, NPY- and SP-immunoreactive
      nerve fibres compared with control specimens was seen in bladder specimens taken
      even as soon as 21 days after distension. This transient depletion of peptidergic
      innervation may partly explain the prolonged voiding problems that often occur
      after acute urinary retention. The depletion of sensory nerves containing SP
      shortly after distension may explain the transient benefit obtained from
      distension therapy in patients with painful bladder disease. It is suggested that
      the increased SP activity during the recovery phase may be related to neurogenic
      inflammation.

PMID- 1380746
TI  - Androgen concentrations in expressed prostatic secretions: no correlation with
      tissue levels.
AB  - In an attempt to determine whether the androgen profiles of the prostate fluid
      (EPS) mirror the concentrations in the prostate tissue, we have measured
      testosterone and dihydrotestosterone (DHT) in EPS and correlated their levels to
      the concentrations found in hyperplastic prostate tissue (BPH) obtained from the
      same 19 patients. Although androgen concentrations in EPS were very high
      (testosterone = 106.7 +/- 81.9 ng/g dry weight; DHT = 54.2 +/- 11.2 ng/g dry
      weight), they did not reflect the concentrations measured in BPH tissue
      (testosterone = 7.56 +/- 1.54 ng/g dry weight; DHT = 10.54 +/- 0.63 ng/g dry
      weight). Additionally the accumulation of tissular DHT usually associated with
      BPH was not mirrored in the EPS specimens which demonstrated a relatively higher
      concentration of testosterone when compared to DHT. In EPS, there was also a very
      strong correlation between testosterone and DHT concentrations (r = 0.89; P less
      than 0.01). We have also measured zinc concentrations in EPS and BPH tissue but
      were unable to detect any relationship between the two parameters. Significantly,
      however, EPS zinc concentrations showed a close correlation with EPS testosterone
      (r = 0.73; P less than 0.01) and DHT (r = 0.69; P less than 0.01) concentrations.

PMID- 1380748
TI  - Cytological detection of copper for the diagnosis of inherited copper toxicosis
      in Bedlington terriers.
AB  - The reliability of a cytological examination of impression smears of the liver
      was investigated in 89 Bedlington terriers by using the rubeanic acid staining
      method for copper and comparing the results with the results of a histological
      examination. Histological examination revealed copper accumulation in the liver
      of 24 dogs. The cytological method had a sensitivity of 0.96 for detecting copper
      toxicosis and a specificity of 1.0. When a grading system for the amount of
      copper was applied, the coefficient of correlation (r) between the cytological
      and histological techniques was 0.917 (P less than 0.0001). It was concluded that
      a cytological examination of impression smears stained with rubeanic acid for
      copper offers a rapid and reliable method for the detection of copper toxicosis
      in Bedlington terriers.

PMID- 1380747
TI  - Modulation of in vitro cell growth of human and murine urothelial tumor cell
      lines under the influence of interleukin-3, granulocyte-, macrophage- and
      granulocyte-colony-stimulating factor.
AB  - To elucidate possible growth-modulating effects of interleukin 3 (IL-3),
      granulocyte-macrophage-colony-stimulating factor (GM-CSF) and granulocyte-colony
      stimulating factor (G-CSF), human transitional cell carcinoma (TCC) cell lines
      T24, RT112, EJ and 647 V were solitarily and continuously exposed to these
      hematopoietic growth factors at concentrations of 1-100 ng/ml. The murine line
      MBT-2 was used as a negative and the colon carcinoma cell line HTB38 as a
      positive control, because of species specificity and known proliferation in
      response to growth factors, respectively. In the T24 TCC-line solitary and
      continuous exposure to IL-3, GM-CSF and G-CSF at the highest concentration of 100
      ng/ml led to a significant proliferation of cell growth in vitro. Significant
      proliferation in the RT112 line was only achieved with continuous exposure to IL
      3 and GM-CSF (100 ng/ml); G-CSF failed to induce growth modulation in the RT112
      line. No significant proliferative effect of any of cytokines administered was
      observed in the 647V line. Exposure of the EJ line to cytokines at the highest
      activity levels had a proliferative effect only in suboptimal growth conditions.

PMID- 1380750
TI  - Lung cancer mortality in Wisconsin: year 2001.
AB  - Lung cancer is the major cause of cancer mortality in Wisconsin, with an
      estimated 2,300 deaths in 1991. The low 5-year survival rate of about 10% in lung
      cancer is primarily attributed to advanced inoperable stage at diagnosis, limited
      response to therapy, and a high incidence of metastatic spread. Since smoking is
      the major etiologic factor associated with lung cancer, this is a largely
      preventable disease. Many current smokers may already have severe
      bronchopulmonary dysplasia or neoplastic changes that may manifest many years
      later. We report on a model developed to evaluate the effect of improved therapy
      for lung cancer patients in the next decade. Based on this model, Wisconsin's
      projected lung cancer mortality is estimated at 2,117 in the year 2001, without
      improved treatment, resulting in nearly 25,000 "years of potential life lost."
      According to this model, a 10% reduction in lung cancer mortality plus a 12-month
      increase in palliation in the year 2001 will "regain" more years of potential
      life lost than the current mortality for stomach, cervical, or uterine cancer.
      Thus, improved cure and palliation for lung cancer patients represents an
      important goal for Wisconsin's medical community.

PMID- 1380749
TI  - [Side effects of administration of gamma globulin preparations in patients with
      primary agammaglobulinemia].
AB  - Eight patients with adverse reactions were observed in a group of 20 primary
      agammaglobulinaemic patients treated with gammaglobulin derivatives. In four
      cases only sporadic reactions were observed, but in 2 cases repeated reactions
      made gammaglobulin therapy impossible. In the remaining two patients a change of
      gammaglobulin derivatives made adequate therapy possible. Possible causes of
      adverse reactions during gammaglobulin treatment and their prevention are
      discussed.

PMID- 1380751
TI  - [Serum cholinesterases as activity parameters in chronic inflammatory bowel
      diseases].
AB  - Significantly decreased levels of serumcholinesterase (CHE) were found in acute
      Crohn's disease (= CD) (3.2 +/- 1.0 KU/L) and acute ulcerative colitis (= UC)
      (3.54 +/- 1.6 KU/L) as compared to patients with mild or quiescient disease (CD:
      5.5 +/- 1.1 KU/L; UC: 5.59 +/- 0.94 KU/L) and healthy controls (5.69 +/- 1.3
      KU/L). Suppression of CHE was most evident in Crohn's colitis (2.98 +/- 1.0 KU/L)
      and extensive UC (2.96 +/- 1.28 KU/L). Intraindividual comparison showed an
      increase of CHE-levels during treatment with steroids and salicylates. There was
      no significant correlation to the reduced bodyweight-levels in severe IBD. Best
      correlations were seen between CHE/albumin (CD: r = +0.61; UC: r = +0.73) and
      CHE/hematocrit (CD: r = +0.50; UC: r = +0.61) in severe inflammatory bowel
      disease. The results of a discriminant analysis showed that CHE-levels can
      predict the degree of activity correctly in the majority of patients with CD and
      UC. It is suggested that the decrease of serumcholinesterase reflects an
      inhibition of liver synthesis as an acute phase response-induced by endotoxins
      and cytokines.

PMID- 1380752
TI  - Occurrence of keratinolytic fungi and related dermatophytes in soils in Cairo,
      Egypt.
AB  - 120 soil samples collected from various sites of Cairo were processed for the
      isolation of keratinophilic fungi by "ToKaVa" hair baiting technique. 22 species
      belonging to 6 genera were isolated viz.: Chrysosporium tropicum, C. indicum, C.
      keratinophilum, C. queenslandicum, C. merdarium, C. anamorph of Arthroderma
      curreyi, C. pannicola, C. lobatum, C. anamorph of Renispora flavissima, C.
      pseudomerdarium, Microascus mangini, Malbranchea gypsea, Ml. State of Uncicarpus
      reesii, Ml. State of Coccidioides immitis, Microsporum gypseum, Mr. distortum Mr.
      audouinii, Mr. fulvum, Trichophyton mentagrophytes, T. terrestre, T. verrucosum
      and Epidermophyton floccosum. The frequency of occurrence of the isolated fungi
      was determined. Microsporum gypseum, Chrysosporium tropicum and Chrysosporium
      indicum were the most frequent species recovered from soil. Most species of
      keratinophilic fungi were isolated from university, public garden and zoo garden.
      The distribution of the isolates are discussed.

PMID- 1380753
TI  - [Immunobiological properties and therapeutic effectiveness of preparations from
      Klebsiella bacteriophages].
AB  - The purified preparations of Klebsiella bacteriophages, viz. the monovalent
      preparation of K. pneumoniae bacteriophage and the polyvalent bacteriophage
      preparation for the treatment of infections caused by K. ozaenae, K.
      rhinoscleromatis scleromatis and K. pneumoniae sensu lato, have been obtained.
      The bacteriophage preparations have proved to be nontoxic and safe for laboratory
      animals after the intraperitoneal injection of these preparations followed by the
      pathomorphological study of the internal organs of the animals. The clinical
      study of the newly developed bacteriophage preparations in the course of the
      treatment of purulent inflammatory diseases in 109 patients has revealed that the
      preparations are not reactogenic and exhibit sufficient effectiveness in the
      therapy of ozena, rhinoscleroma and Klebsiella infections with different
      localization of the infectious process.

PMID- 1380754
TI  - [Value of prostate-specific antigen as prognostic factor of metastatic cancer of
      the prostate].
AB  - This paper examines the behaviour of PSA in 70 patients with metastatic prostate
      cancer. PSA serum concentration, prior to therapy, was directly related to the
      tumoral mass and inversely related to the histological degree, which does not
      constitute a prognostic factor with regard to the disease evolution. Within 3
      months of therapy, PSA concentration decreased more noticeably in clinically
      responding patients, down to less than 10 ng/ml in 93% of them. Also, this level
      represented a prognostic factor with regard to the free-of-progression interval
      of the disease.

PMID- 1380755
TI  - [Medical treatment of benign prostatic hyperplasia in patients with high surgical
      risk].
AB  - Eight patients with prostate adenoma and high surgical risk were given leuprolide
      in depot. Prostate volume decreased by 44.7% after 3 months of treatment and by
      58.9% at six months. Two of the 7 patients were resident vesical catheter
      carriers, 28% re-started spontaneous miction.

PMID- 1380756
TI  - Modulation of GABAA-gated C1- currents in nigral neurons in slices.

PMID- 1380758
TI  - GABAA and NMDA receptor function during chronic administration of ethanol.

PMID- 1380757
TI  - Modulation of GABAergic transmission by ethanol.

PMID- 1380759
TI  - Modulation of GABA receptor-channel complex by alcohols and general anesthetics.

PMID- 1380760
TI  - Evoked endogenous taurine release from cultured cerebellar neurons.

PMID- 1380761
TI  - Taurine protection of lungs in hamster models of oxidant injury: a morphologic
      time study of paraquat and bleomycin treatment.

PMID- 1380762
TI  - Taurine and niacin offer a novel therapeutic modality in prevention of chemically
      induced pulmonary fibrosis in hamsters.
AB  - The bleomycin (BL)-hamster model of interstitial pulmonary fibrosis (IPF) is
      generally associated with increased lung lipid peroxidation, measured as
      malondialdehyde equivalent (MDAE), calcium and collagen content; and superoxide
      dismutase (SOD), prolyl hydroxylase (PH) and poly(ADP-ribose) polymerase
      activities. We found that combined treatment with taurine in drinking water (1%)
      and niacin IP (250 mg/kg) daily, significantly decreased the BL-induced increases
      in lung MDAE and calcium content, and SOD, PH and poly(ADP-ribose) polymerase
      activities. This treatment almost completely ameliorated the BL-induced increases
      in the lung collagen accumulation as well. Findings of a similar nature were also
      demonstrated when taurine (2.5%) and niacin (2.5%) were supplemented in the diet
      of hamsters used in the same BL model of IPF. The diet supplemented with taurine
      (2.5%), niacin (2.5%), or taurine (2.5%) + niacin (2.5%) also reduced AD-induced
      increases in lung collagen accumulation, phospholipids, MDAE and SOD activity. It
      was concluded that diet supplemented with taurine and/or niacin would completely
      or partially ameliorate chemically-induced pulmonary fibrosis.

PMID- 1380763
TI  - The short term effect of peripherally administered brain-gut peptides on gastric
      acid secretion in rats.
AB  - Certain brain gut-peptides are known to either stimulate or inhibit gastric acid
      secretion in several species after direct injection into the central nervous
      system. However there is inconsistency of published results on the gastric acid
      secretory response to some of these peptides after peripheral administration in
      different experimental systems. Seven peptides, namely neurotensin (NT),
      substance P, cholecystokinin (CCK), thyrotropin releasing hormone (TRH), human
      calcitonin (hCT), rat calcitonin-gene-related peptide (rCGRP) and bombesin, all
      known to modulate gastric acid secretion after central administration, were
      initially screened for activity after peripheral (subcutaneous) injection of 10
      micrograms/kg body weight in a single rat model. Peptides showing an effect were
      retested at lower doses. Despite the inherent variability of the gastric acid
      secretory response in the non-anaesthetized pylorus ligated rat, a standardized
      experimental design confirmed that reproducible and statistically valid results
      could be obtained. The technical feasibility of using a one hour collection
      period as might be appropriate for short acting peptides was demonstrated by the
      significant dose dependent inhibitory activity of salmon calcitonin. In this
      model, NT and substance P had no significant effect on either volume or
      concentration of acid secreted, CCK showed a slight stimulation of acid output,
      and TRH, hCT, rCGRP and bombesin all inhibited acid output; CGRP and bombesin
      were active at 10 and 100-fold lower doses. The potent and inhibitory activity of
      bombesin in this system is in disagreement with other publications reporting no
      effect or variable stimulatory effect in rats. Time and dose dependent responses
      in our rat system indicate that this apparent discrepancy may be explained by the
      short duration of action of bombesin.

PMID- 1380766
TI  - Hepatitis C virus antibody in Swaziland.

PMID- 1380765
TI  - The efficacy of cyclosporin A, FK-506 and prednisolone to modify the adoptive
      transfer of experimental allergic encephalomyelitis (EAE).
AB  - The in vitro potency of the immunosuppressants Cyclosporin A (CsA), FK-506 and
      Prednisolone was assessed using the adoptive transfer model of EAE in the Lewis
      rat. Co-culture of encephalitogen-sensitised splenic leukocytes with Prednisolone
      did not inhibit the transfer of disease to naive histocompatible recipients
      despite significant suppression of neuroantigen-stimulated leukocyte
      proliferation by the drug. The addition of CsA (100 nM) to cultures inhibited the
      induction of adoptive EAE but a lower dose of the agent (10 nM) did not prevent
      the development of clinico-histopathological signs of disease. FK-506 (1 nM) was
      100 times more effective than CsA at suppressing adoptive EAE thus emphasising
      the usefulness of the model in determining the relative efficacy of compounds to
      modify cell-dependent autoimmune disease.

PMID- 1380764
TI  - Formation of histamine-releasing activity from albumin by medium conditioned by
      endotoxin-stimulated rat peritoneal macrophages.
AB  - Incubation of bovine serum albumin (BSA), rat serum albumin or rat plasma with
      medium conditioned by endotoxin stimulated rat peritoneal macrophages produced an
      activity that released histamine from isolated rat serosal mast cells. The amount
      of histamine-releasing activity (HRA) produced increased with the length of the
      incubation period, with the concentration of albumin, with the number of
      macrophages stimulated, and with the duration of exposure of the macrophages to
      endotoxin. Moreover, the formation of the HRA showed a dependency on the pH of
      the incubation medium with an optimum at pH 4.5. Boiling the medium conditioned
      by stimulated macrophages before its incubation with albumin or including the
      acid protease inhibitor, pepstatin with the conditioned medium prevented the
      formation of HRA. The generation of HRA was not inhibited by pretreatment of the
      macrophages with the inhibitor of protein synthesis, cycloheximide. Media from
      macrophages not stimulated with endotoxin failed to generate HRA. Histamine
      release from mast cells in response to the HRA was inhibited by pretreatment of
      the cells with antimycin A and deoxyglucose or by preincubation in Ca-free
      Locke's solution containing a calcium chelating agent. When injected
      intradermally into anesthetized Evan's Blue treated rats, the generated HRA
      produced a change in vascular permeability that was prevented by the H1
      antagonist, diphenhydramine. Treatment of the HRA with carboxypeptidase A reduced
      its ability to stimulate histamine release from mast cells. Histamine-Releasing
      Peptide (HRP), a neurotensin-related octapeptide, shown previously by us to be
      formed by the action of cathepsin D or pepsin on albumin, was identified by
      radioimmunoassay in acid:acetone extracts of the histamine-releasing activity. It
      is concluded that the formation of HRA is due to the actions of enzymes released
      from macrophages acting on albumin. It is suggested that such histamine-releasing
      activity could be formed during the later stages of the inflammatory response and
      that HRP is one of the peptides present.

PMID- 1380768
TI  - The study cellular subpopulations in peripheral blood from a normal reference
      group population (blood donors).
AB  - The spectacular development of monoclonal antibodies against cellular antigens an
      technology such as flow cytometry allow the investigation of cellular
      subpopulations that until now have been unknown. At the same time, the functional
      study of these subpopulations becomes of maximal interest, as this information
      could have future applications for pathological processes. Due ti this basic need
      for information, we have studied diverse lymphocytic subpopulations in a normal
      population that serves as a reference group, using the following antigens: CD3,
      CD4, CD8, CD20, CD45RA, CD25, LAM1, CD29, CD11b and CD23. Some of these
      subpopulations had not been previously studied in a normal reference group.

PMID- 1380767
TI  - [Substance P: immuno-allergic implications].
AB  - Substance P is a decapeptide which forms part of the group known as
      neuropeptides, that is, peptides released by some neurones such as the slow
      conducting C fibres and the rapid-conducting A-delta fibres. These neurones
      belong to the category of non-adrenergic non-cholinergic nerves (NANC), which
      perform their action through a mechanism known as "axonic reflex". This mechanism
      is an antidromic stimulation which produces a secretion of neuropeptides,
      especially substance P. It is known that substance P, once released, is able to
      exert a number of actions including among others inflammatory and bronchospastic
      activities and a stimulation of the immunologic system. Other effects attributed
      to this substance are an increase in capillary permeability and oedema and the
      perpetuation of certain conditions such as asthma, rhinitis and chronic urticaria
      or hives. The production, metabolism and actions of this neuropeptide are
      described.

PMID- 1380769
TI  - Distribution of CA 125 in adenocarcinomas. An immunohistochemical study of 481
      cases.
AB  - To determine the distribution of CA 125 in adenocarcinomas, formalin-fixed,
      paraffin-embedded tissue from 481 cases of adenocarcinoma from a variety of
      primary sites were studied using a monoclonal antibody to CA 125 (B27.1) and an
      avidin-biotin immunohistochemical technique. Positive reactivity was most common
      in adenocarcinomas of the endocervix, ovary, and endometrium (61% to 94%).
      However, relatively frequent positive reactions also were seen in adenocarcinomas
      of the pancreas (48%) and bile ducts (56%). Adenocarcinomas of the breast, lung,
      thyroid, distal esophagus/stomach, and liver (hepatocellular carcinoma) showed
      positive reactions in 7% to 20% of cases. Staining of rare tumor cells was seen
      in 2 of 45 colonic adenocarcinomas and in 1 of 61 prostatic adenocarcinomas. No
      reactivity was seen in the 54 renal cell carcinomas studied. Although CA 125 is
      most commonly present in gynecologic adenocarcinomas, it is also produced by some
      adenocarcinomas from many other sites. Immunostaining for CA 125 may be helpful
      in ruling out renal cell carcinoma in certain clinical settings.

PMID- 1380770
TI  - A rare lymphoepithelial cyst of the pancreas.
AB  - Reported is a case of a rare lymphoepithelial cyst of the tail of the pancreas
      that developed in a young man with no symptoms. To the authors' knowledge, it is
      the first case described to be entirely situated within the pancreas, thus
      confirming its pancreatic origin. Biologic behavior appears to be entirely
      benign, and the primary importance of its recognition is in the distinction from
      cystic malignant neoplasms.

PMID- 1380771
TI  - The heart in Tangier disease. Severe coronary atherosclerosis with near absence
      of high-density lipoprotein cholesterol.
AB  - Cardiac necropsy findings are described in a 72-year-old man with Tangier disease
      whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein
      cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level
      was 1.4 mg/dL, and who had coronary artery bypass grafting for severe
      atherosclerotic coronary artery disease. At necropsy, 24 of the 72 (33%) 5-mm
      segments of the 4 major (right, left main, left anterior descending, and left
      circumflex) native coronary arteries and 4 of the 27 (15%) 5-mm segments of the
      saphenous vein aortocoronary bypass conduits were narrowed by more than 75% in
      cross-sectional area by atherosclerotic plaques. The plaques were composed
      primarily (91% to 97%) of fibrous tissue. Oil red O staining, polarized light
      microscopy, and electron microscopy revealed cholesterol deposits in the plaques
      and in the walls of coronary arteries, saphenous vein grafts, and aorta. Such
      deposits also were found in foam cells of histiocytic origin, fibroblasts in all
      four cardiac valves, and in Schwann cells of cardiac nerves.

PMID- 1380772
TI  - Systemic polyclonal B-immunoblastic proliferation with marked peripheral blood
      and bone marrow plasmacytosis.
AB  - The clinical and pathologic features of a case of acute systemic polyclonal B
      immunoblastic proliferation characterized by pronounced peripheral blood and bone
      marrow plasmacytosis and infiltration of the hepatic portal areas by
      immunoblasts, plasma cells, and lymphocytes are reported. Clinical and laboratory
      findings during the acute phase and long-term follow-up support the diagnosis of
      a benign process, possibly related to Pseudomonas aeruginosa septicemia. The
      patient experienced a dramatic clinical recovery on administration of high-dose
      intravenous corticosteroids. Pathologists should be aware of this entity so as
      not to confuse it with non-Hodgkin's lymphoma or a form of plasma cell dyscrasia.

PMID- 1380773
TI  - Filtration dynamics and natriuretic response to volume expansion in humans.
AB  - We used differential solute clearances and a theoretical analysis of glomerular
      ultrafiltration and dextran sieving to characterize the hemodynamic response of
      nine healthy humans to infusion of isoncotic, 5% albumin in saline or saline
      vehicle alone. During albumin infusion (10.2 +/- 0.2 ml.kg-1.30 min-1) plasma
      volume increased by 18%, but oncotic pressure rose by only 0.8 mmHg. Despite the
      hypervolemia, renal blood flow (RBF) declined by 140 ml/min and glomerular
      filtration rate (GFR) declined by 16 ml/min during the infusion. RBF increased
      progressively postinfusion, exceeding baseline by 135 ml/min after 4 h; GFR was
      restored to baseline. Although oncotic pressure declined by 2 mmHg, a similar
      transient decline in GFR (-13 ml/min) was associated also with infusion of saline
      vehicle alone (9.4 +/- 0.3 ml.kg-1.30 min-1), which increased plasma volume by
      9%. Sieving coefficients of dextrans (radius 32-42 A) were lowered during and
      after either infusion, a phenomenon that we compute to reflect a reduction in
      glomerular pore size. Assuming that the transcapillary hydraulic pressure
      difference was not lowered, we calculate that there was a simultaneous depression
      of the ultrafiltration coefficient (Kf) during volume expansion with saline and
      possibly also to a lesser extent with albumin. The hypofiltration during either
      infusion delayed the onset of a natriuretic response until the filtered sodium
      load was restored to baseline in the postinfusion period. We propose that the net
      effect of changes in intracapillary pressures and Kf during volume expanding
      infusions is to transiently lower GFR, thereby preventing the human kidney from
      mounting an immediate natriuretic response to acute hypervolemia.

PMID- 1380776
TI  - Familial thrombocytopenia with micromegakaryocytes.
AB  - Chronic thrombocytopenia was noted in two siblings and a first cousin. The
      initial impression was of immune thrombocytopenic purpura (ITP) with decreased
      megakaryocytes. One patient had splenectomy for presumed chronic ITP but showed
      no improvement. Bone marrow buffy coat slides were examined in the three children
      with thrombocytopenia, four normal controls, and five children with "classic"
      acute ITP. Megakaryocyte size, maturation, and ploidy were determined with Wright
      Giemsa and Feulgen-stained material. Mean megakaryocyte diameters were 23.1
      microns in the three related patients, 30.8 microns in normal controls, and 63.1
      microns in children with "classic" acute ITP. Many "micromegakaryocytes" were
      noted in the three related children with chronic thrombocytopenia. An exhaustive
      family history was obtained, which showed multiple points of consanguinity. These
      patients represent an apparently new autosomal recessive disorder of
      megakaryocytopoiesis, characterized by disturbed megakaryocyte ploidization and
      maturation. More sensitive recognition of micromegakaryocytes should be attempted
      in children with atypical chronic thrombocytopenia, familial history of
      thrombocytopenia, or patients who have ITP and who have not responded to initial
      therapy.

PMID- 1380774
TI  - Dual action of phosphonoformic acid on Na(+)-phosphate cotransport in opossum
      kidney cells.
AB  - Phosphonoformic acid (PFA, foscarnet) was found to exert both an inhibitory and a
      stimulatory effect on Na(+)-dependent Pi transport in opossum kidney (OK) cells.
      When added in the uptake media, PFA produced a dose-dependent inhibition of Na(+)
      Pi cotransport. PFA had no effect on the Na(+)-dependent transports of methyl
      alpha-D-glucopyranoside (AMG) or L-alanine or on amiloride-sensitive Na(+)-H+
      antiport. The inhibition of Na(+)-Pi cotransport was competitive [inhibitory
      constant (Ki) = 6.0 mM], reversible by dilution, and solute specific. When OK
      cells were incubated with PFA for longer time periods (1-15 h), the Na(+)-Pi
      uptake measured after removal of PFA was significantly increased, i.e.,
      "upregulated." The extent of Na(+)-Pi cotransport upregulation was dependent on
      time (greater than or equal to 30 min) and dose of PFA (2-10 mM). The increase in
      Na(+)-Pi cotransport by upregulation with PFA was due to higher apparent Vmax
      with no change in apparent Michaelis constant (Km) for Pi and was solute
      specific: uptakes of AMG or L-proline were not changed. Removal of PFA from
      culture medium resulted in a fast reversal of upregulation. Upregulation was not
      inhibited by cycloheximide, actinomycin D, or cordycepin. Solute-specific
      increase of Na(+)-Pi cotransport was also found when measured in apical membrane
      vesicles isolated from OK cells. Thus PFA exerts a dual action on the Na(+)-Pi
      cotransporter of OK cells: 1) acute, competitive inhibition and 2) after
      prolonged exposure it increases Na(+)-Pi uptake, probably by insertion of Na(+)
      Pi cotransporters into apical membrane.

PMID- 1380775
TI  - Characteristics of calcium currents in rabbit portal vein myocytes.
AB  - The properties of voltage-dependent Ca2+ channels were studied in isolated portal
      vein myocytes using the whole cell voltage-clamp method. Ca2+ currents (ICa) were
      identified based on their activation and inactivation potential, their dependence
      on external Ca2+ ([Ca2+]o), their suppression by organic or inorganic Ca2+
      channel blockers, their augmentation by BAY K 8644, and their insensitivity to
      tetrodotoxin or alterations in external Na+ ([Na+]o). Changing the holding
      potential from -90 to -40 mV decreased ICa from 4.6 +/- 0.6 to 2.0 +/- 0.3 pA/pF
      at 0 mV but did not shift its voltage dependence significantly. The voltage
      dependence of steady-state inactivation and activation was represented by
      Boltzmann distributions with the following parameters: inactivation, half-maximal
      voltage (V0.5) = -32 +/- 7 mV and slope factor (k) = 6.1 +/- 0.2 mV; activation,
      V0.5 = -15 +/- 4 mV and k = 5.6 +/- 0.6 mV. Doubling the [Ca2+]o increased ICa
      and shifted the voltage dependence of its activation and inactivation by
      approximately 10 mV toward more positive potentials without altering the window
      currents. Substituting Na+, Ba2+, or Sr2+ for Ca2+ as the charge carrier through
      the Ca2+ channel slowed the rate of its inactivation and shifted its voltage
      dependence toward more negative potentials. Divalent selectivity of the Ca2+
      channel showed an apparent concentration dependence: at 2 mMISr less than IBa =
      ICa, while at 10 mM ICa less than ISr = IBa. Because 50-100 microM ethylene
      glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid abolished the
      apparent concentration dependence of the divalent ion selectivity, this
      phenomenon was attributed to a high Ca2+ selectivity of the channel. Our data
      support the presence of only one type of Ca2+ channel in rabbit portal vein
      myocytes with characteristics similar to the L-type Ca2+ channel described in
      other cells, but with somewhat different divalent selectivity, holding potential,
      and [Na+]o dependence.

PMID- 1380777
TI  - Impairment of cerebral biogenic amine synthesis in a patient receiving high-dose
      methotrexate.
AB  - A transient acute neurologic syndrome occurred in a 15-year-old boy receiving
      high-dose methotrexate (MTX) for acute lymphoblastic leukemia. Cerebrospinal
      fluid analysis revealed a decrease of homovanillic acid and 5-hydroxyindoleacetic
      acid concentrations with a rise of biopterin levels. These findings suggest that
      MTX can induce a transient alteration of the metabolism of tetrahydrobiopterin
      leading to the defect of biogenic amine neurotransmitter synthesis.

PMID- 1380778
TI  - A study of keratin expression in benign familial chronic pemphigus.
AB  - We studied keratin expression in the involved and uninvolved skin of six benign
      familial chronic pemphigus (BFCP) patients, using monoclonal antibodies specific
      for various keratin polypeptides and immunohistopathologic techniques. Normal and
      psoriatic (i.e., hyperproliferative) skin specimens served as controls. The
      uninvolved BFCP epidermis showed keratin profiles identical to that of normal
      epidermis. In the acantholytic epidermal segments of the involved BFCP skin, some
      of the lower suprabasal acantholytic cells failed to express keratin polypeptides
      10 and 11 (Moll's catalog). This delay in expression of suprabasal keratins was
      not accompanied by an expression of hyperproliferative keratin polypeptide 16.
      Also, some of the lower suprabasal acantholytic cells of the involved BFCP
      epidermis retained staining by the antikeratin KS-1A3 antibody, which in the
      normal, psoriatic, and uninvolved epidermis was limited to the basal cell layer.
      Staining for keratin polypeptide 18 was negative in the epidermis of all four
      types of specimens. We believe that the delay in suprabasal keratin expression in
      the involved BFCP epidermis was more likely secondary to the acantholysis (i.e.,
      "arrest of differentiation" due to acantholysis) rather than due to a primary
      defect in keratin expression.

PMID- 1380779
TI  - Markers of keratinocyte maturation and differentiation.

PMID- 1380780
TI  - Apocrine type of cutaneous mixed tumor with follicular and sebaceous
      differentiation.
AB  - Eight cases of apocrine (tubular branching lumina) type cutaneous mixed tumors
      with follicular and sebaceous differentiation are presented. All eight tumors
      arose on facial skin; six patients were male and two were female. The lesions
      showed a cystic or nodular clinical appearance and were surgically excised.
      Histopathological examination confirmed the diagnosis of apocrine type of
      cutaneous mixed tumor in each case. Follicular differentiation consisted of (a)
      keratinous cysts with infundibular keratinization (infundibular differentiation);
      (b) hair bulbs with papillary mesenchyma, matricial differentiation with
      basophilic, transitional, and shadow cells, trichohyaline granules, vellous hair
      shafts, and clear cells of the outer root sheath (anagen differentiation); and
      (c) epithelial columns composed of inner cells with plump oval nuclei and scant
      cytoplasm, and similar cells at the periphery that were arranged in a palisade,
      resembling the inferior segment of a normal hair follicle in telogen. Sebaceous
      differentiation was represented by mature sebaceous cells, either as single cells
      or as small islands, within epithelial tracts of the tumor. The proportion of the
      areas showing these different types of differentiation varied among lesions, but
      some follicular differentiation was always present, whereas three cases lacked
      sebaceous differentiation. Immunohistochemical analysis in three cases with
      respect to their eccrine or apocrine differentiation showed contradictory results
      as in a previously reported series of cutaneous mixed tumors. The presence of
      follicular and sebaceous differentiation in the apocrine (tubular branching
      lumina) type of cutaneous mixed tumor is a confirmation of the apocrine nature of
      this neoplasm as well as an expression of the common embryologic derivation of
      all elements of the folliculosebaceous-apocrine unit.

PMID- 1380781
TI  - Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell
      carcinomas and their absence in basal cell carcinomas. Indicator of tumor type
      and differentiation.
AB  - Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in
      lectin binding have been reported to accompany epidermal cell differentiation,
      marking alterations in membrane sugars during this process. The presence of UEA I
      (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been
      used as a marker for terminally differentiated (committed) keratinocytes. In this
      article, we report the presence of UEA-I-binding sites on squamous keratinocytes
      of well-differentiated squamous cell carcinomas, with patchy loss of UEA I
      positivity on poorly differentiated cells of squamous cell carcinomas, suggesting
      a possible use for this technique in the rapid assessment of less differentiated
      areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal
      cell carcinomas may be related to an inability of cells comprising this tumor to
      convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting
      in an inability of basal cell carcinoma cell to undergo terminal differentiation
      into a committed keratinocyte.

PMID- 1380782
TI  - Food allergy: identification of the major IgE-binding component of peach (Prunus
      persica).
AB  - Since peaches are a relatively common cause of food allergy, we set out to
      identify the allergens involved. With the use of a panel of 48 sera from patients
      allergic to peach, we demonstrate that most of the allergenicity of that fruit is
      confined to the skin, rather than to the flesh of peaches, and corresponds to a
      protein doublet with an estimated molecular weight of 8-10 kD.

PMID- 1380783
TI  - Circulating elevated levels of soluble CD23, interleukin-4, and CD20+CD23+
      lymphocytes in atopic subjects with elevated serum IgE concentrations.
AB  - Circulating IgE protein levels, leukocyte counts, lymphocyte subsets, IL-4, and
      soluble CD23 levels were quantitated in 43 atopic and 19 nonatopic subjects. Mean
      values of IgE protein levels, total eosinophil counts, CD20+CD23+ cells (B cells
      with low-affinity IgE receptor), IL-4 and sCD23 levels were elevated in atopic
      patients compared with nonatopic controls. The results suggest that sCD23, IL-4,
      and CD20+CD23+ lymphocytes may play a role in the increased production of IgE in
      atopic subjects in a manner similar to that observed by other investigators in
      prior in vitro studies.

PMID- 1380784
TI  - Soy hypersensitivity in children with food allergy.
AB  - To evaluate humoral (IgE antibodies) and clinical (positive challenge test) soy
      hypersensitivity prevalence, we studied 317 children (271 boys and 100 girls)
      with a median age of 5 months (range 1-120) who visited the Division of Allergy
      and Clinical Immunology of the Pediatric Department of the University of Roma "La
      Sapienza" because of histories and symptoms suggestive of food allergy. Atopic
      dermatitis (AD) was present in 247/317 children (78%), diarrhea in 19 (6%),
      urticaria in 22 (7%), and rhinitis and/or asthma in 29 (9%). All children
      underwent diagnostic procedures including family and personal history, physical
      examination, PRIST, and RAST to cows milk (CM), egg, wheat, soy, and
      Dermatophagoides pteronyssinus (Dpt). Open challenge tests to soy were performed
      in the hospital under observation and with emergency equipment at hand. The
      prevalence of humoral sensitization to CM was 54%, to egg 46%, to Dpt 35%, to
      wheat 24%, and to soy 22%. Only five children had IgE only to soy; six to soy and
      egg; and 58 to soy, CM, and egg. Only ten children (3%) had positive challenge to
      soy and only five of them had IgE to soy. RAST had a sensitivity of 0.69, a
      specificity of 0.83, a negative predictive value of 0.77, and a positive
      predictive value of only 0.06.

PMID- 1380785
TI  - A pore transport model for pulmonary alveolar epithelium.
AB  - Hydrodynamic heteropore flow models for transport of solutes across alveolar
      epithelial tissue have been developed. A two-size cylindrical pore model and a
      similar parallel-plate model were formulated, tested and used to predict
      effective pore sizes from literature data on transport in bullfrog, canine and
      rat lungs. The best fit equivalent pore-size estimates were obtained using a
      modified, nonlinear least squares procedure, with alveolar surface area to volume
      ratio (S/V) and small-pore area fraction of total pore area as parameters. Small
      pore and large-pore width estimates of 4 nm (84% of total flow area) and 10 nm,
      respectively, with an average deviation of 20% from experimentally derived
      permeabilities were obtained from the bullfrog alveolar epithelium parallel-plate
      pore model (13 solutes, diameters 0.3 to 2.8 nm). The equivalent cylindrical pore
      model diameter estimates were 5 nm and 10 nm, with small-pore area fraction and
      percentage deviations similar to the parallel-plate model estimates. Eighty-eight
      percent of the bulk water driven by a sucrose osmotic gradient was predicted to
      be transported through the small pores. The rat alveolus parallel-plate pore
      model (6 solutes) yielded small-pore and large-pore widths of 0.4 nm and 50 nm,
      respectively. Clearance rate-constant data for dextran macromolecules (3,000 to
      250,000 Daltons), using a single parallel-plate pore model, resulted in a pore
      width estimate of 98 nm for canine alveoli with an average deviation of the
      predicted rate constants of 18% from literature experimental values. In all cases
      tested, the parallel-plate pore model predicted lower small-pore size estimates
      than did the cylindrical pore model, and both models had appreciably smaller
      percentage deviations from experimental data than previous models.

PMID- 1380786
TI  - Comparison of the effects of intragastric infusions of equal volumes of water,
      dioctyl sodium sulfosuccinate, and magnesium sulfate on fecal composition and
      output in clinically normal horses.
AB  - A Latin square design was used to compare the effects of laxatives and a
      corresponding volume of water on gastrointestinal tract function in 4 healthy
      horses. Horses were intragastrically infused with each of the following: dioctyl
      sodium sulfosuccinate (DSS; 50 mg/kg of body weight); magnesium sulfate (0.5 g/kg
      -low dosage); magnesium sulfate (1.0 g/kg--high dosage); and an equal volume of
      water (6 L) given as a control infusion. From 5 to 33 hours after the high dosage
      of magnesium sulfate, feces were slightly softer than usual in all horses. In 1
      horse, DSS caused mild colic, hyperpnea, and diarrhea from 0.3 to 3 hours after
      administration. After all laxative treatments and the control infusion, fecal
      output, fecal water, number of defecations, and fecal water percentage were
      greater during the first 6 and 12 hours, compared with each subsequent 6-hour
      period (P less than 0.05). The high dosage of magnesium sulfate had greater
      effect on fecal output and fecal water than did the low dosage and control
      infusion (P less than 0.05). However, this effect preceded arrival of the liquid
      transit marker, polyethylene glycol, and magnesium at their highest
      concentrations in feces by 12 to 18 hours. Compared with the control infusion,
      none of the laxative treatments affected excretion of polyethylene glycol and
      plastic particulate markers, nor did they increase water consumption. It was
      concluded that the response to intragastric infusions may involve reflex
      mechanisms in the gastrointestinal tract and that these responses could be used
      for treatment of colon impactions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380787
TI  - Hemostatic defects associated with two infusion rates of dextran 70 in dogs.
AB  - We investigated changes in hemostatic function after infusion of 6% dextran 70
      (high molecular weight dextran) at 2 rates. Six healthy dogs underwent 3
      regimens: 20 ml of dextran/kg of body weight administered in 1 hour (trial A), 20
      ml of dextran/kg administered in 30 minutes (trial B), and 0.9% sodium chloride
      solution as a control administered over 1 hour to achieve hemodilution equivalent
      to that for 20 ml of dextran/kg (trial C). Before and at 2, 4, 8, and 24 hours
      after the start of trials A and B, we measured PCV, total solids (TS)
      concentration, amount of von Willebrand factor antigen (vWf:Ag), factor VIII
      coagulant activity (VIII:C), prothrombin time, activated partial thromboplastin
      time (APTT), platelet retention in a glass bead column, and buccal mucosa
      bleeding time (BMBT). Values were not obtained at 8 and 24 hours for trial C.
      Saline-induced changes in hemostasis were significant (P less than 0.05) from
      baseline throughout the sample collection period. Significant differences (P less
      than 0.05) between trial A and control were observed for vWf:Ag, VIII:C, BMBT,
      APTT, TS, and PCV values at 2 hours, and for VIII:C at 4 hours. Significant
      differences (P less than 0.05) between trial B and control were observed for
      APTT, TS, and PCV values at 2 hours, and for vWf:Ag, VIII:C, BMBT, APTT, TS, and
      PCV values at 4 hours. During trials A and B, mean values of analytes
      infrequently deviated from reference intervals, and clinical signs of bleeding
      were not observed in any dog.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380788
TI  - L-696,229 specifically inhibits human immunodeficiency virus type 1 reverse
      transcriptase and possesses antiviral activity in vitro.
AB  - L-696,229 (3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-pyridin-2 (1H)-one) is a
      specific inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) activity that possesses antiviral activity in cell culture
      (W.S. Saari, J.M. Hoffman, J.S. Wai, T.E. Fisher, C.S. Rooney, A.M. Smith, C.M.
      Thomas, M. E. Goldman, J. A. O'Brien, J. H. Nunberg, J. C. Quintero, W. A.
      Schleif, E. A. Emini, and P. S. Anderson, J. Med. Chem. 34:2922-2925, 1991). In
      the present study, the RT-inhibitory activity and antiviral properties were
      characterized in detail. The inhibition of RT activity was template-primer
      dependent with 50% inhibitory concentrations of 0.018 to 0.50 microM and was
      noncompetitive with respect to deoxynucleoside triphosphates. L-696,229 inhibited
      RT activity in a mutually exclusive manner with respect to either
      phosphonoformate or azidothymidine triphosphate and was a weak partial inhibitor
      of the RNase H activity associated with HIV-1 RT. The compound did not
      significantly inhibit other retroviral or cellular polymerases at 300 microM.L
      696,229 inhibited the spread of HIV-1 infection in cell cultures with all cell
      types and viral isolates tested, including human peripheral blood mononuclear
      cells and a virus isolate resistant to azidothymidine.

PMID- 1380789
TI  - Identification of the human immunodeficiency virus reverse transcriptase residues
      that contribute to the activity of diverse nonnucleoside inhibitors.
AB  - The reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is
      potently inhibited by a structurally diverse group of nonnucleoside compounds.
      These include pyridinone derivatives, tetrahydroimadazo[4,5,1-j,k][1,4]
      benzodiazepin-2(1H)-one and -thione, and BI-RG-587 (nevirapine). The compounds
      act noncompetitively, by an unknown mechanism, with respect to template-primer
      and nucleotide substrates. Despite a high degree of similarity between the HIV-1
      and HIV-2 RTs, the HIV-2 enzyme is totally insensitive to these inhibitors. Using
      a novel method for joining DNA sequences, we have exploited this difference
      between the two enzymes to identify the regions of the RT that contribute to the
      compounds' inhibitory activities. The relative in vitro sensitivities of HIV
      1/HIV-2 chimeric and site-specific mutant enzymes were determined. Sensitivity to
      inhibition was largely, though not exclusively, dependent upon the RT region
      defined by amino acid residues 176 to 190, with specific contributions by
      residues 181 and 188. The region defined by residues 101 to 106 was found to
      functionally interact with the domain from 155 to 217. In addition, the
      functional equivalence of the three inhibitor groups was shown.

PMID- 1380790
TI  - Effector-assisted refolding of recombinant tissue-plasminogen activator produced
      in Escherichia coli.
AB  - Recombinant tissue-plasminogen activator (r-tPA), expressed in Escherichia coli
      cells in an aggregated form, was solubilized with a strong chaotrope in the
      absence of any reducing agent. The solubilized molecule was reactivated by a
      procedure that was developed to mimic the physiological conditions optimal for
      the functional folding and activity of the native protein. The use of partially
      purified fibrinogen, as a source of fibrin (the effector), is shown to facilitate
      the reactivation process and increase its yield by at least a factor of two. The
      yield of the process is also shown to be particularly dependent on the
      recombinant protein concentration. At a concentration level of 3-3.7 mg r-tPA/L
      in the reactivation mixture, up to a 90% yield of activity was obtained.
      Purification of the activated form of r-tPA was achieved with a two-step column
      chromatography scheme. This included a gel filtration step on a Sephadex G-50
      column followed by an affinity chromatography step on a lysine-sepharose column.
      The product was composed of roughly equal amounts of one-chain and two-chain t
      PA. The feasibility of using a two water-soluble polymeric phase system, with a
      centrifugal partition chromatography (CPC), in scaling up the reactivation
      process or the purification step was also evaluated.

PMID- 1380791
TI  - [Enterovesical fistula secondary to leiomyosarcoma].
AB  - We report an unusual case of an enterovesical fistula caused by leiomyosarcoma
      infiltrating the intestinal wall and urinary bladder. The patient had previously
      presented recurrent urinary tract infection for one year. Although he has
      residual tumor, so far this elderly patient has survived for three years post
      operatively without further antineoplastic treatment.

PMID- 1380792
TI  - Use of endotracheal silicone stents for relief of tracheobronchial obstruction.
AB  - In this article we describe our initial experience with bifurcated and
      longitudinal silicone stents that can be inserted entirely endoscopically. A
      total of 10 patients were stented; half had upper airways obstruction resulting
      from malignant disease and half had anastomotic obstruction after single-lung (3
      patients), double-lung (1 patient), or heart-lung transplantation (1 patient).
      All patients derived immediate relief of life-threatening stridor. Stents were in
      place for between 5 days and 2 1/2 years (mean, 232.9 days). In the patients with
      malignant disease, the stents have provided effective relief from stridor for the
      remainder of their lives. In the transplant recipients, the medium-term results
      are encouraging, with the stents providing effective relief from stridor,
      although the longitudinal stents have been associated with distal migration,
      requiring that the stents be replaced on up to five occasions. The stents have
      not been associated with infection in the nonimmunosuppressed patients, and
      during the relatively short follow-up period there has been no tissue reaction to
      the material.

PMID- 1380793
TI  - The hypothalamo-cerebellar projection in the rat: origin and transmitter.
AB  - Hypothalamic neurons projecting to cerebellum were identified by retrograde
      tracing with wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the rat.
      Selective D-[3H]aspartate labelling was used to investigate whether any of these
      connections may use excitatory amino acids as transmitters. The WGA-HRP
      experiments revealed that the hypothalamo-cerebellar fibers have their main
      origins in the lateral, dorsal and posterior hypothalamic areas, and the tubero
      mammillary nucleus, while smaller numbers of cells were observed in tuber
      cinereum, the anterior hypothalamic area, and the periventricular and
      paraventricular nuclei. After injections of D-[3H]aspartate into the cerebellar
      cortex, intense labelling of the olivocerebellar climbing fiber system was
      observed, but hypothalamic cells were not retrogradely labelled with this
      selective tracer. The absence of D-[3H]aspartate labelling indicates that
      hypothalamo-cerebellar neurons lack specific uptake mechanisms for excitatory
      amino acids, but it does not entirely preclude the possibility that some of these
      hypothalamic neurons may use such transmitters. Many cerebellar projecting cells
      were located in the tubero-mammillary nucleus, which is known to contain
      histaminergic and GABAergic neurons, and it was concluded that part of the
      hypothalamo-cerebellar pathways may use histamine and/or GABA as transmitters.
      The transmitter remains unknown for other parts of the hypothalamo-cerebellar
      pathways.

PMID- 1380794
TI  - Cloning and expression of an amylase gene from Streptococcus bovis in Escherichia
      coli.
AB  - An amylase gene was identified in a Streptococcus bovis 033 lambda gtWES lambda B
      genomic library. Using a starch overlay and a Congo red-iodine staining
      procedure, amylase positive clones could be identified by zones of clearing. Ten
      amylase positive clones were identified using this procedure. The clone chosen
      for further study, lambda SBA105, contained an insert of approximately 7.5 kb.
      The insert was mapped, and subcloning localized the amylase gene to a region of
      approximately 3.1 kb. Cloning of the 3.1 kb amylase fragment into pUC18 in both
      orientations revealed that the amylase gene was transcribed from its own
      promoter. Amylase activity was expressed by the Escherichia coli subclones and
      was found to be largely associated with the cytoplasmic fraction. Southern
      hybridization of genomic DNA from the amylolytic strains, S. bovis 033, S. bovis
      077, Butyrivibrio fibrisolvens 194 and 195 revealed a single hybridizing band in
      S. bovis 033 DNA only. This indicates that the amylase gene from S. bovis may
      differ from the amylases of these other amylolytic bacteria.

PMID- 1380795
TI  - Detection of glycoproteins in Borrelia burgdorferi.
AB  - The presence of carbohydrates on proteins of Borrelia burgdorferi, the causative
      agent of Lyme disease, was investigated by using a digoxigenin labeling method
      together with Schiff staining and N-glycosidase F assay. The two major outer
      surface exposed proteins of 31 kDa and 34 kDa showed to be glycosylated and gel
      filtration high pressure liquid chromatography (HPLC) of proteins of B.
      burgdorferi metabolically labeled with 14C-N-acetylglucosamine revealed the
      incorporation of the carbohydrate into the glycosyl residue of these proteins.

PMID- 1380796
TI  - Identification of the hepatocyte mitogen in bovine spleen as heparin-binding
      growth factors.
AB  - Growth promoting activity for rat hepatocytes in bovine spleen was identified as
      three heparin-binding growth factors. All the features tested, such as heparin
      affinity, molecular mass, cross reactivity with antibody, and partial amino acid
      sequence, indicated that one of the three factors was identical to FGF-1
      (fibroblast growth factor-1, acidic FGF), another one was related to FGF-2
      (fibroblast growth factor-2, basic FGF), whereas it was more potent for
      hepatocytes than the FGF-2 purified from bovine brain. The third one was eluted
      from heparin-Sepharose column at 0.75M NaCl, of which activity was not abolished
      by anti-FGF-1 or FGF-2 antibodies. In addition, the mitogenic effect of this
      factor was synergistic with that of HGF (hepatocyte growth factor), a known
      potent hepatocyte mitogen, suggesting that it is a novel growth factor for
      hepatocytes.

PMID- 1380797
TI  - Expression of TAPA-1 in preimplantation mouse embryos.
AB  - TAPA-1 is a member of a new family of evolutionarily conserved transmembrane
      proteins which may be involved in regulation of cell growth and/or cell
      signalling. We have examined the temporal pattern of TAPA-1 RNA expression during
      mouse development. Using a sensitive reverse transcription/polymerase chain
      reaction assay, we show that TAPA-1 RNA is present in oocytes, fertilized eggs
      and cleavage stage embryos.

PMID- 1380799
TI  - Template. Phosphorothioate oligonucleotides duplexes as inhibitors of HIV-1
      reverse transcriptase.
AB  - We have investigated the interaction between a number of 14 mers phosphorothioate
      oligonucleotides and HIV-1 reverse transcriptase. Two methods were used to
      measure the affinity of the analogs for the enzyme. In the first, the
      oligonucleotide or its duplex with Poly(rl) were used as inhibitors of the enzyme
      using Poly(rA).(dT)14 as template primer. In the second, the oligonucleotides or
      their duplexes were used to displace a fluorescent template primer complex of
      known affinity from its binding site on reverse transcriptase. The two methods
      gave the same relative order of affinity. Phosphorothioate
      oligodeoxyribonucleotides had a much higher affinity than oligo(dC)14 and it was
      increased on hybridization. Quantitatively similar results were obtained for
      S(dC)14 or its analog with bases in the alpha-configuration. Of the analogs
      tested, only S(dC)14 showed priming activity.

PMID- 1380798
TI  - Molecular cloning of rabbit CAP-50, a calcyclin-associated annexin protein.
AB  - CAP-50 is a member of annexin family proteins which binds specifically to
      calcyclin in a Ca2+ dependent manner (Tokumitsu. H., Mizutani. A., Minami. H.,
      Kobayashi. R., and Hidaka. H. (1992) J. Biol. Chem. 267,8919-8924). The cDNA
      representing the rabbit form of this protein has been cloned from rabbit lung
      cDNA library. Sequence analysis of two overlapping clones revealed a 81
      nucleotides 5'-nontranslated region, 1512-nucleotides of open reading frame, a
      672-nucleotides 3'-nontranslated region, and a poly(A) tail. Authenticity of the
      clones was confirmed by comparison of portions of the deduced amino acid sequence
      with eight sequences of proteolytic peptides obtained from rabbit lung protein.
      CAP-50 cDNA encodes a 503 residue protein with a calculated M(r) of 54,043 and
      shows that the protein is composed of four imperfect repeats and hydrophobic N
      terminal region. C-terminal region including four imperfect repeats shows 58.1%
      identity with human synexin (annexin VII), 48.0% identity with annexin I, 47.4%
      identity with annexin II, 60.1% identity with annexin IV, 54.5% identity with
      annexin V. Hydrophobic N-terminal region composed of 202 amino acid residues is
      not homologous with other annexin proteins suggesting that CAP-50 is a novel
      member of annexin family proteins.

PMID- 1380800
TI  - Adhesion promotes transcellular leukotriene biosynthesis during neutrophil
      glomerular endothelial cell interactions: inhibition by antibodies against CD18
      and L-selectin.
AB  - Eicosanoid formation by transcellular routes can amplify the levels and types of
      lipid mediators within a local milieu. To evaluate the role of adhesion in this
      process, we assessed the influence of mAb against adhesion molecules on LTC4
      generation by PMN-endothelial cell interaction. Transcellular LTC4 generation was
      initiated by addition of fMLP to coincubations of GM-CSF-primed PMN and TNF
      activated endothelial cells cultured from kidney glomeruli. Both PMN-endothelial
      cell adhesion and transcellular LTC4 generation were inhibited by mAb against
      leukocyte L-selectin and CD18. These results indicate that cytokine-treated PMN
      and endothelial cells generate LTC4 via transcellular routes by receptor
      triggered mechanisms. They suggest that adhesion promotes transcellular
      eicosanoid biosynthesis and that adhesion molecules may also be targets for
      blockade of transcellular biosynthesis of lipid mediators.

PMID- 1380801
TI  - Rapamycin inhibits the phosphorylation of p70 S6 kinase in IL-2 and mitogen
      activated human T cells.
AB  - Phosphorylation of 40S ribosomal protein S6 is regulated in part by the mitogen
      activated p70 S6 kinase (p70s6k). Following the addition of IL-2 to the IL-2
      dependent human cell line Kit225, or mitogenic activation of resting human T
      cells, a rapid phosphorylation of p70s6k was observed by immunoblotting.
      Rapamycin (RAP), a potent suppressor of T-cell proliferative responses, markedly
      inhibited the phosphorylation of p70s6k induced by IL-2 in Kit225 cells or by the
      mitogens added to resting T cells. Other immunosuppressants such as cyclosporin A
      or an FK506 analogue were without effect. Moreover, the effect of RAP was
      restricted to p70s6k; it did not inhibit the phosphorylation of p90rsk, another
      kinase which utilizes the S6 protein as a substrate. These data indicate for the
      first time that RAP may target the pathway leading to p70s6k phosphorylation
      during human T-cell proliferation.

PMID- 1380802
TI  - Mapping the orientation of an antigenic peptide bound in the antigen binding
      groove of H-2Kb using a monoclonal antibody.
AB  - The major histocompatibility complex class I molecules are receptors for
      intracellular peptides, both of self and non-self origin. When non-self peptides
      (eg., pathogen derived) are bound to the class I molecules, they form ligands for
      T cell receptors resulting in antigen specific lysis of the infected cells by
      cytotoxic T lymphocytes. Therefore, an understanding of the process of antigen
      recognition requires the precise definition of the structural features of the
      bimolecular complex formed by a single well defined antigenic peptide bound to
      the class I molecule. A strategy using antibodies was developed to probe the
      structural features of the H-2Kb containing a defined peptide in the antigen
      cleft. We report that the binding surface area of a Kb specific monoclonal
      antibody (28-13-3s) includes residues in the alpha 1 (Gly56 and Glu58) and alpha
      2 (Trp167) helices of Kb thus, binding across the antigen binding groove. When
      cells treated with the antigenic peptide of vesicular stomatitis virus, N52-59,
      and its alanine substituted analogs were tested for 28-13-3s binding, it was
      found that position 1 of the peptide also forms a part of the antibody binding
      site. This finding strongly supports the positioning of the N-terminus of N52-59
      proximal to pocket A, thus, assuming an orientation parallel to the alpha 1
      helix.

PMID- 1380803
TI  - Alteration of RNA I metabolism in a temperature-sensitive Escherichia coli rnpA
      mutant strain.
AB  - E. coli strain A49 carries the themosensitive mutation in the rnpA gene encoding
      the protein component of RNase P, a tRNA-processing enzyme. Two small RNAs were
      highly accumulated in the A49 carrying derivatives of ColE1-type plasmids, at
      nonpermissive temperature. Characterization of these RNAs showed that they were
      the processed or degraded products derived from RNA I, which is the negative
      controller of ColE1-type plasmid replication. These derivatives of RNA I only
      differ in size at the 5' ends. The data of their degradation and synthesis
      kinetics suggest that they are intermediates of RNA I metabolism.

PMID- 1380804
TI  - A model system for tumor angiogenesis: involvement of transforming growth factor
      alpha in tube formation of human microvascular endothelial cells induced by
      esophageal cancer cells.
AB  - Tumor growth is dependent on angiogenesis, which is thought to be mediated
      through growth factors, such as transforming growth factor-alpha (TGF-alpha) and 
      beta (TGF-beta), epidermal growth factor (EGF), and basic fibroblast growth
      factor (bFGF), produced by tumor cells. We have developed a model system for
      tumor angiogenesis in vitro: tube formation of human omentum microvascular
      endothelial (HOME) cells in type I collagen gels when these cells are co-cultured
      with tumor cells. Exogenously added TGF-alpha induced tube formation of HOME
      cells in collagen gel. In contrast, TGF-beta inhibited the TGF-alpha-induced tube
      formation of endothelial cells. We investigated whether tube formation could be
      induced in HOME cells in collagen gel when the HOME cells were co-cultured with
      three esophageal cancer cell lines, TE1, TE2, and TE5. TE1 and TE2 cells
      expressed both TGF-alpha and TGF-beta mRNA, but the level of TGF-alpha mRNA in
      TE2 was found to be much lower than in TE1 cells. TE5 did not express either TGF
      alpha or TGF-beta. The tube formation of HOME cell was induced when they were co
      cultured with TE1 cells, while both TE2 and TE5 cell lines induced tube formation
      at much lower rates than TE1. TE1-induced tube formation of HOME cells was
      specifically blocked by co-administration of anti-TGF-alpha-antibody, but not by
      anti-bFGF-antibody. The present study suggests that, in our model system,
      esophageal tumor angiogenesis is partly controlled by TGF-alpha, possibly through
      a paracrine pathway.

PMID- 1380805
TI  - Platelet-derived growth factor activation of gastric mucosal calcium channels.
AB  - Gastric mucosal calcium channel complex was isolated from the solubilized
      epithelial cell membranes by affinity chromatography on wheat germ agglutinin.
      The complex following labeling with [3H]PN200-100 was reconstituted into
      phospholipid vesicles which exhibited active 45Ca2+ uptake. The channels
      responded in a dose dependent manner to dihydropyridine calcium antagonist, PN200
      110, which at 0.5 microM exerted maximal inhibitory affect of 66% on 45Ca2+
      uptake, while a 52% enhancement in 45Ca2+ uptake occurred with a specific calcium
      channel activator, BAY K8644. On platelet-derived growth factor (PDGF) binding in
      the presence of ATP, channels showed an increase in protein tyrosine
      phosphorylation of 55 and 170kDa subunits of calcium channel. Such phosphorylated
      channels following reconstitution into vesicles displayed a 78% greater 45Ca2+
      uptake. The results point towards the importance of PDGF in the regulation of
      gastric mucosal calcium homeostasis.

PMID- 1380806
TI  - Enhanced photorelaxation in aorta, pulmonary artery and corpus cavernosum
      produced by BAY K 8644 or N-nitro-L-arginine.
AB  - Segments of endothelium-denuded aorta, pulmonary arterial rings and strips of
      corpus cavernosum from rabbits were superfused with Krebs medium. Photorelaxation
      elicited by ultraviolet light (366 nm) was significantly enhanced by either BAY K
      8644 (20 nM) or N-nitro-L-arginine (100 and 500 microM) and was associated with
      increased cyclic GMP. This action of both drugs was greater in pulmonary artery
      than aorta and corpus cavernosum and persisted in vascular rings for 90 min after
      drug removal. The effect was significantly attenuated by hemoglobin (10 microM)
      but was unaltered by superoxide dismutase (30 u/ml). The mechanism of such
      photosensitization is presently unclear.

PMID- 1380807
TI  - Solubilization of ribosomes in reverse micelles.
AB  - Pig liver ribosomes have been solubilized in reverse micelles constituted by bis
      (2-ethyl hexyl) sodium sulfosuccinate (AOT) in isooctane and 3.6% water, v:v. The
      micellar ribosomal solutions are transparent, show no significant scattering and
      permit direct spectroscopic observation of the ribosomes to be made. Ultraviolet
      absorption and circular dichroic spectra have been recorded and indicate that the
      ribosomes maintain in the micellar environment their structural integrity. Some
      possible applications of these micellar systems are discussed.

PMID- 1380808
TI  - Serotonin stimulates a Ca2+ permeant nonspecific cation channel in hepatic
      endothelial cells.
AB  - The contraction of hepatic endothelial cell fenestrae after exposure to serotonin
      is associated with an increase in intracellular Ca2+ which is derived from
      extracellular Ca2+, is inhibited by pertussis toxin and is not associated with
      activation of phosphoinositol turnover or cAMP. Using cell-attached and excised
      patches in primary cultures of rat hepatic endothelial cells, we identified a
      serotonin-activated channel with conductance of 26.4+/-2.3 pS. The channel was
      also permeant to Na+, K+ and Ca++ but not to anions. In cell-attached patch
      recordings, addition of serotonin to the bath significantly increased channel
      activity with Ca2+ or Na+ as the charge-carrying ions. This channel provides a
      mechanism whereby serotonin can raise the cytosolic Ca2+ concentration in hepatic
      endothelial cells.

PMID- 1380809
TI  - Modulation of K+ channels by hydrogen peroxide.
AB  - External application of hydrogen peroxide (H2O2) was found to inhibit the time
      dependent fast inactivation process of three cloned voltage-gated K+ channels
      expressed in Xenopus oocytes: KShIIIC, KShIIID and HukII. As expected from
      kinetic models where some channels are still opening while a significant fraction
      of channels is already inactivated there was a large increase in current
      magnitude concomitant to inactivation block. The channels otherwise functioned
      normally. The effects of H2O2 were specific (other cloned voltage-gated K+
      channels were not affected), and reversible, the currents returned to normal upon
      removal of the H2O2. H2O2 is produced during normal metabolism; it could act as a
      modulator of excitability through effects on K+ channels if effective local
      concentrations are reached in neuronal regions close to the channel. KShIIIC and
      KShIIID currents are very similar to an O2-sensitive K+ current present in type I
      cells of the carotid body which is believed to underlie the modulation of
      excitability of these cells by changes in arterial O2 pressure. H2O2 has been
      proposed as an intermediary between O2 and cellular response in the carotid body;
      our results provide support for this model.

PMID- 1380810
TI  - The suppression of hepatic cytochrome P4504A mRNA mediated by the interferon
      inducer polyinosinic acid.polycytidylic acid.
AB  - Interferon and interferon inducers are well known to depress the cytochrome P450
      dependent hepatic mixed-function oxidase system and cause a decrease in the
      capacity of the liver to metabolize drugs and xenobiotics. In this study we have
      shown that the interferon-mediated changes in an induced form of hepatic
      cytochrome P450 (CYP4A) are mediated via a depression in the levels of mRNA as
      assessed by Northern blot and slot blot analyses using a 20-base synthetic
      oligodeoxyribonucleotide hybridization probe. Rats were pretreated with
      clofibrate to maximize CYP4A mRNA levels prior to the administration of
      polyinosinic acid.polycytidylic acid (poly IC), an alpha/beta interferon inducer.
      Hepatic CYP4A mRNA levels were decreased by 49 and 30% at 6 and 24 hr,
      respectively, following poly IC administration. In hepatic microsomes cytochrome
      P450 and functional CYP4A as measured by lauric acid hydroxylation, were not
      affected at 6 hr, but were depressed by 39 and 27%, respectively, 24 hr following
      poly IC administration. These results suggest that interferon depresses induced
      levels of hepatic drug metabolism by lowering the level of cytochrome P450 mRNAs
      and subsequent synthesis of cytochrome P450 apoproteins.

PMID- 1380811
TI  - Neuropharmacological mechanisms of capsaicin and related substances.
AB  - Capsaicin activates poorly myelinated primary afferent neurons, many of which are
      polymodal nociceptors. Activation is accompanied by membrane depolarization and
      the opening of a unique, cation-selective, ion channel which can be blocked by
      the polyvalent dye ruthenium red. The capsaicin-induced activation is mimicked by
      resiniferatoxin, a potent analogue, and by low pH. Activation is mediated by a
      specific membrane receptor which can be selectively and competitively antagonized
      by capsazepine. Repetitive administration of capsaicin produces a desensitization
      and an inactivation of sensory neurons. Several mechanisms are involved including
      receptor inactivation, block of voltage activated calcium channels, intracellular
      accumulation of ions leading to osmotic changes, and activation of proteolytic
      enzyme processes. Systemic and topical capsaicin produces a reversible
      antinociceptive and anti-inflammatory action after an initial undesirable algesic
      effect. Capsaicin analogues, such as olvanil, have similar properties with
      minimal initial algesic activity. Antinociception produced by capsaicin does not
      involve neurotoxicity, sensory neuropeptide depletion or activity at peripheral
      receptors; rather, systemic capsaicin produces antinociception by activating
      capsaicin receptors on afferent nerve terminals in the spinal cord. Spinal
      neurotransmission is blocked by a prolonged inactivation of sensory
      neurotransmitter release. However, local or topical applications of capsaicin
      block C-fibre conduction and inactive neuropeptide release from peripheral nerve
      endings. These mechanisms account for localized antinociception and the reduction
      of neurogenic inflammation, respectively.

PMID- 1380812
TI  - Expression of the cytochrome P4502E and 2B gene families in the lungs and livers
      of nonpregnant, pregnant, and fetal hamsters.
AB  - Members of the cytochrome P4502E and 2B gene families have been implicated in the
      activation of nitrosamines to reactive species capable of binding to cellular
      macromolecules and initiating tumor formation in various rodent species. This
      study was initiated to determine the relative prevalence of these isozymes and
      their response to ethanol during pregnancy and late gestation. Nonpregnant and
      pregnant hamsters were given a 10% ethanol solution in their drinking water for
      10 days (gestation days 5-15) prior to being killed. RNA blot analysis of liver
      and lung tissue from nonpregnant, pregnant, and fetal hamsters demonstrated
      tissue-specific expression of CYP2E and 2B in adult and fetal animals. The levels
      of RNA expression of both P450s in fetal hamsters were less than 30% of
      nonpregnant adult values. In pregnant hamsters, the hepatic levels of CYP2E and
      2B RNAs were decreased compared to nonpregnant animals. In contrast, the
      pulmonary levels of CYP2B RNA were increased in pregnant versus non-pregnant
      hamsters, while no effect of pregnancy on the levels of CYP2E RNA was seen.
      Although rats contain a single CYP2E1 gene transcript. Northern analysis
      demonstrated the presence of 1.8 and 2.8 kb bands in both liver and lung tissue
      of the hamster. Pretreatment with ethanol had little effect on the levels of
      either P450 RNA species in the lungs or livers of nonpregnant, pregnant, and
      fetal hamsters. These results demonstrate differences in the levels of expression
      of members of the CYP2E and 2B gene families during pregnancy and late gestation
      compared to nonpregnant adult hamsters. Fetal animals, like the adults,
      apparently respond to ethanol treatment by altering the levels of these P450
      isozymes at the post-transcriptional level.

PMID- 1380813
TI  - Transmembrane signalling in T cells.
AB  - Transmembrane signalling to activate T cells to proliferate and differentiate is
      a complex multistep process. It is the focus of much current interest, mostly
      because a selective and well-controlled inhibition of the process will allow
      regulation, or at least modulation, of the immune response. Here, Sandor
      Damjanovich and colleagues review the contributions of Hungarian scientists to
      the understanding of signalling in lymphocytes in particular, and cell activation
      in general.

PMID- 1380814
TI  - Synthetic peptides in the search for T- and B-cell epitopes.
AB  - In this article, Eva Rajnavolgyi describes two aspects of the rigorous
      application of organic chemistry to the task of synthesizing peptides that induce
      immune responses. First, the development of viral peptides that activate T and B
      cells without the need for carrier molecules and secondly, the production of a
      new generation of immunologically inert carrier molecules.

PMID- 1380815
TI  - Allorecognition by NK cells: nonself or no self?
AB  - The issue of antigen recognition by NK cells is complex, fascinating and, as yet,
      unresolved. This article reviews recent research on the repertoire of human NK
      cell clones for the recognition of different allogeneic cells, and summarizes the
      studies, most of which have been performed in mice, that implicate the MHC in NK
      cell recognition. It goes on to provide a common conceptual framework within
      which these different systems may be understood.

PMID- 1380816
TI  - Image analysis of Feulgen-stained NIH/3T3 cells transformed with DNA of 4
      nitroquinoline 1-oxide treated human breast epithelial cells.
AB  - The nuclear phenotypes of Feulgen-stained NIH/3T3 cells transformed with 4
      nitroquinoline 1-oxide (4NQO) treated, human breast epithelial cell (HBEC) DNA
      were studied by scanning microspectrophotometry and image analysis and compared
      with data obtained for nontransformed cells and for NIH/3T3 cells under ras
      oncogene transfecting situations. The Feulgen-DNA content of the individual
      nuclei (NQ1, NQ2, and NQ3 phenotypes) of the transformed cells was found not to
      be deeply affected, although presence of chromatin structures resembling double
      minutes could be verified in part of the metaphases of the transformed cells. On
      the other hand, the chromatin supraorganization of these cells showed some
      changes involving increased (NQ2, NQ3) or decreased (NQ1) levels of condensation.
      The changes in chromatin packing states, however, were of small magnitude
      compared with those reported for NIH/3T3 cells transfected with a c-H-ras
      oncogene or an N-ras-containing MCF-7 cell DNA. It was assumed that the
      transformation of the NIH/3T3 cells is not always necessarily accompanied by high
      levels of chromatin condensation. The transformation of the NIH/3T3 cells induced
      by the 4NQO-treated HBEC DNA and particularly the changes in chromatin
      condensation in these transformed cells could not be attributed merely to a ras
      activation elicited by the carcinogen. It is suggested that a more complex
      transforming mechanism is involved, probably owing to the fact that a whole
      genomic DNA of the 4NQO-treated HBEC has been used for transfection.

PMID- 1380817
TI  - Effects of cholinergic drugs on cell interactions during fertilization and early
      development of the sea urchin Paracentrotus lividus.
AB  - In the present work we tested the effects of cholinergic drugs on the early
      development of P. lividus. Fertilization was performed in the presence of
      cholinergic drugs, and the embryos were fixed after 2 hours, when the controls
      (untreated) completed the second segmentation cleavage. We identified four
      classes of stages in the development of the embryos affected by the drugs, i.e.:
      unhatched zygotes, first cleaved stage, second cleaved stage (= unaffected), and
      anomalous embryos. Statistical analysis indicated that that drugs with analogous
      action mechanism caused similar alterations in the distribution of the treated
      embryos in these four classes. This finding supports the hypothesis of the
      presence of a complete "pre-nervous" cholinergic system, with a true cholinergic
      role. It is tempting to speculate that this system is involved in the first cell
      to cell interactions during early segmentation and possibly in the block to
      polyspermy.

PMID- 1380818
TI  - Spatial distribution of active genes implicated in the regulation of insulin-like
      growth factor stimulatory loops in human decidual and placental tissue of first
      trimester pregnancy.
AB  - We have previously shown that the insulin-like growth factor-2 (IGF-2) gene is
      partially coexpressed with the IGF-1 and -2 receptor genes in proliferative
      cytotrophoblasts of the human extraembryonic tissue. Here we show that high
      levels of IGF-2 gene expression are not restricted to the embryonic tissue but
      can also be found in the decidua compacta. The IGF-2 gene is thus expressed at
      high levels in the mesenchymal stroma of the decidua to establish potentially
      short-range communication with primarily IGF-1 receptor-positive mesenchymal
      stroma cells. Conversely, the glandular and surface epithelia coexpress the IGF-1
      receptor and IGF-1 genes, while the IGF-2 gene is not detected above background
      levels. The potential control mechanisms of these cell-cell signalling pathways
      were investigated by the analysis of the spatial distribution of active IGF
      binding proteins (IGFBP) genes. The IGFBP-3 gene is coexpressed with the IGF-2
      gene in proliferative cytotrophoblasts of the embryonic placenta. While active
      IGFBP-1 and -2 genes in our hands cannot be detected in the embryonic placenta,
      all three IGFBP genes are expressed in complex and overlapping patterns in the
      decidua compacta. The results are discussed in terms of how the various IGFBP
      genes may operate in different cell types to restrict IGF local stimulatory
      pathways.

PMID- 1380819
TI  - Communicable disease mortality: now you see it, now you don't.

PMID- 1380820
TI  - Cholera situation in the Americas.

PMID- 1380821
TI  - AIDS surveillance in the Americas.

PMID- 1380822
TI  - Expression of the tumour suppressor gene p53 in oral cancer.
AB  - In this preliminary series, the product of the tumour suppressor gene p53 was
      detected in 12/15 cases of oral squamous cell carcinoma (SCC) and in two cases of
      leukoplakia. The tumours either expressed the mutant form of p53 throughout the
      specimen or contained focal areas of positive cells. p53 expression was commonly
      observed in tumours obtained from patients who were heavy smokers and drinkers
      suggesting that alterations in the p53 gene may be one of the sites of genetic
      damage in this group of patients.

PMID- 1380824
TI  - Influence of acylation on the channel characteristics of gramicidin A.
AB  - The influence of acylation on the conductance, average duration, and channel
      forming potency of channels formed by gramicidin A analogues was investigated
      using single-channel and multichannel techniques. Lauroyl-, myristoyl-, palmitoyl
      , stearoyl-, and oleoylgramicidin A were prepared by covalent coupling of that
      fatty acid to the C-terminal ethanolamine group. Acylation of gramicidin A does
      not affect the single-channel conductance or the minichannel frequency in
      diphytanoylphosphatidylcholine/n-decane black lipid membranes. However, the
      average duration of all acylgramicidin channels was increased approximately 5
      fold as compared to unmodified gramicidin A, which has a duration of 0.9 s at 200
      mV applied potential. Somewhat surprisingly the rate of channel formation of the
      acylgramicidins is decreased relative to gramicidin A: lauroyl- and
      stearoylgramicidin are approximately 200 times less effective in channel
      formation as compared to gramicidin A. We conclude that channels formed by the
      acylgramicidins and by gramicidin A are structurally and conformationally
      equivalent.

PMID- 1380823
TI  - Molecular and channel-forming characteristics of gramicidin K's: a family of
      naturally occurring acylated gramicidins.
AB  - The gramicidin K family is a set of naturally occurring acylated linear peptides
      in which a fatty acid is esterified to the ethanolamine hydroxyl of either
      gramicidin A or C, and possibly also to gramicidin B (Koeppe, R. E., II,
      Paczkowski, J. A., & Whaley, W. L. (1985) Biochemistry 24, 2822-2826). These
      acylated gramicidins form membrane-spanning channels in planar lipid bilayers and
      therefore constitute a model system with which to study the structural and
      functional consequences of acylation on membrane proteins. This paper serves to
      characterize further the channels formed by acylated gramicidins A and C and to
      demonstrate that these channels are structurally equivalent to the channels
      formed by the standard gramicidins. We also present additional evidence for the
      ester linkage in the natural acylated gramicidins A and C and identify the fatty
      acyl chains.

PMID- 1380825
TI  - Molecular cloning and tissue distribution of alternatively spliced mRNAs encoding
      possible mammalian homologues of the yeast secretory pathway calcium pump.
AB  - Rat stomach and testis cDNAs corresponding to two alternatively spliced mRNAs
      encoding variants of a P-type ion-transport ATPase that closely resembles the
      yeast secretory pathway Ca2+ pump have been isolated and characterized. A partial
      kidney cDNA was identified previously using an oligonucleotide probe
      corresponding to part of the sarcoplasmic reticulum Ca(2+)-ATPase [Gunteski
      Hamblin, A., Greeb, J., & Shull, G.E. (1988) J. Biol. Chem. 263, 15032-15040]. In
      the present study, we first isolated and characterized a stomach cDNA that
      contains the entire coding sequence. The 919 amino acid enzyme has the same
      apparent transmembrane organization and contains all of the conserved domains
      present in other P-type ATPases. Northern blot analyses demonstrate that 3.9- and
      5-kilobase mRNAs corresponding to the cDNA were present in all tissues examined,
      suggesting that the protein it encodes performs a housekeeping function. Rat
      testis also contained a 3.7-kilobase mRNA that hybridized with a probe from the
      5' end of the stomach cDNA but did not hybridize with a probe from the 3' end.
      Cloning and characterization of cDNAs corresponding to the smaller testis mRNA
      revealed that it is derived from the same gene but encodes a variant of the
      enzyme in which the C-terminal residue, Val-919, is replaced by the sequence Phe
      919-Tyr-Pro-Lys-Ile-923. Similarity comparisons show that the two enzymes are
      more closely related to the known Ca2+ pumps than to other P-type
      ATPases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380826
TI  - Active site studies of human immunodeficiency virus reverse transcriptase.
AB  - The active site of human immunodeficiency virus reverse transcriptase (HIV1-RT)
      was probed using three group-specific reagents: phenylglyoxal (PG), N
      ethylmaleimide (NEM), and pyridoxal 5'-phosphate (PLP). The inactivation of HIV1
      RT by arginine-specific PG was found to be completely protected against by adding
      primer-template. The potential active site arginine was localized to position 277
      in the primary structure, suggesting that the polymerase domain of the enzyme
      should be considered as extending at least this far from the N terminus. The
      sulfhydryl-modifying reagent NEM completely inhibits NY5-HIV1-RT, which contains
      a cysteine at position 162, and such inhibition is protected against by primer
      template. However, it does not strongly inhibit LAV-HIV1-RT, in which C162 is
      replaced by S162, indicating that while C162 may be at or near the active site or
      interact allosterically with primer-template, it is not essential for activity.
      The lysine-specific reagent PLP was found to be a noncompetitive inhibitor with
      respect to both primer-template [poly(rA).oligo(dT)] and dTTP. The latter result
      differentiates HIV1-RT from other RTs, for which PLP has been shown to be a
      competitive inhibitor with respect to dTTP.

PMID- 1380827
TI  - Mapping function to structure in a channel-blocking peptide: electrostatic
      mutants of charybdotoxin.
AB  - Electrostatic interactions between charybdotoxin (CTX), a specific peptide pore
      blocker of K+ channels, and a Ca(2+)-activated K+ channel were investigated with
      a genetically manipulable recombinant CTX. Point mutations at certain charged
      residues showed only small effects on the binding affinity of the toxin molecule:
      Lys11, Glu12, Arg19, His21, Lys31, and Lys32. Replacement by Gln at Arg25, Lys27,
      or Lys34 strongly decreased the affinity of the toxin. These affinity changes
      were mainly due to large increases of toxin dissociation rates without much
      effect on association rates, as if close-range interactions between the toxin and
      its receptor site of the channel were disrupted. We also found that the
      neutralization of Lys27 to Gln removed the toxin's characteristic voltage
      dependence in dissociation rate. Mutation and functional mapping of charged
      residues revealed a molecular surface of CTX which makes direct contact with the
      extracellular mouth of the K+ channel.

PMID- 1380828
TI  - Analysis of side-chain organization on a refined model of charybdotoxin:
      structural and functional implications.
AB  - The spatial organization of side chains on a refined model of charybdotoxin is
      presented. First, the structural role of two groups of well-defined, low
      accessible side chains (Thr3, Val5, Val16, Leu20, Cys33 and Leu20, His21, Thr23,
      Cys17, Cys35) is discussed. These side chains are conserved in three out of the
      five known scorpion toxins acting on K+ channels. Interestingly, they are not
      conserved in scyllatoxin which presents a slightly different secondary structure
      organization. Second, the spatial organization of all positively charged residues
      is analyzed. Comparison with the results presented by Park and Miller [(1992)
      Biochemistry (preceding paper in this issue)] shows that all functionally
      important positive residues are located on the beta-sheet side of the toxin.
      These results are different from those obtained by Auguste et al. [(1992)
      Biochemistry 31, 648-654] on scyllatoxin, which blocks a different type of K+
      channel. This study shows, in fact, that functionally important positive residues
      are located on the helix side of the toxin. Thus, charybdotoxin and scyllatoxin,
      which present the same global fold, interact with two different classes of K+
      channels by two different parts of the motif.

PMID- 1380829
TI  - Structure-function analysis of DNA polymerase-beta using monoclonal antibodies:
      identification of a putative nucleotide binding domain.
AB  - DNA polymerase-beta was purified from Novikoff hepatoma and used as an antigen in
      an in vitro immunization system to produce monoclonal antibodies. These reagents
      surprisingly showed cross-reactivity to a number of proteins, including several
      DNA polymerases. Nearly all of these proteins possess nucleotide binding sites,
      which suggested the potential value of using the monoclonals to elucidate
      structure-function relationships within polymerase-beta. Furthermore, these
      antibodies were able to partially neutralize (40-50%) polymerase-beta activity,
      and this effect could be blocked by dNTP1 but not by dNMP or rNTP. The limited
      neutralization phenomenon is at least partially explained by the weak binding
      affinity of these antibodies. Scatchard analysis of immunoprecipitation data
      predicted a Kd of 1.8 x 10(-8) M. Epitope mapping studies showed that the region
      of polymerase-beta recognized by one of the monoclonal antibodies is within
      residues 235-335, and sequence homology studies indicated that the epitope is
      probably located in the region of amino acids 283-320. At least a portion of this
      area, namely residues 301-308 and 311-315, appears to be part of a nucleotide
      binding domain which has sequence homology with a portion of the highly conserved
      ATP binding site in adenylate kinase.

PMID- 1380830
TI  - Importance of asparagine-61 and asparagine-109 to the angiogenic activity of
      human angiogenin.
AB  - Two distinct regions of angiogenin are critical for angiogenic activity: a
      catalytic site capable of cleaving RNA and a noncatalytic site, encompassing
      residues 60-68, which may bind to an endothelial cell-surface receptor [Hallahan,
      T. W., Shapiro, R., & Vallee, B. L. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 2222
      2226]. We have now shown that Asn-61 is an essential residue within the cell
      binding site and that in addition a segment containing Asn-109 is part of this
      site. Both asparagines undergo nonenzymatic deamidation during long-term storage
      or treatment at alkaline pH. While the isolated desamido-61 and desamido-109
      derivatives retain nearly full enzymatic activity, their angiogenic activity on
      the chicken embryo chorioallantoic membrane is markedly attenuated and they do
      not inhibit angiogenin-induced neovascularization. Tryptic peptide mapping and
      Edman degradation demonstrate that the isolated deamidated derivatives primarily
      contain isoaspartic rather than aspartic acid at the positions in question (83%
      for desamido-61, greater than 99% for desamido-109). Aspartic acid replacement of
      Asn-61 and Asn-109 by site-directed mutagenesis results in the same
      ribonucleolytic and angiogenic activities as those of the spontaneous deamidation
      products. However, the aspartyl derivatives differ strikingly from their
      isoaspartyl counterparts in that they do inhibit angiogenin-induced angiogenesis.
      These results indicate that the combination of ribonucleolytic activity and
      receptor-binding capacity is not sufficient for angiogenic activity and that Asn
      61 and Asn-109 within the noncatalytic site are required for some additional
      function, as yet undefined.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380831
TI  - Characterization of gramicidin A in an inverted micellar environment. A combined
      high-performance liquid chromatographic and spectroscopic study.
AB  - We have investigated the conformational adaptability of gramicidin A incorporated
      into reverse micelles of sodium bis(2-ethylhexyl)sulfosuccinate
      (AOT)/isooctane/water, a so far unexplored "host" membrane-mimetic model system
      for this peptide. A high-performance liquid chromatographic strategy previously
      developed for the study of gramicidin in phospholipid vesicles and normal
      micelles [Bano et al. (1989) FEBS Lett. 250, 67; Bano et al. (1991) Biochemistry
      30, 886] has been successfully extended to this system. The method has permitted
      the separation of peptide conformational species, namely, double-stranded dimers
      and monomers, and an accurate quantitation of their proportion in the inverted
      micellar environment. It has been demonstrated that, once inserted in the
      micelle, the double-stranded dimers undergo a dissociation process toward a
      thermodynamically stable monomeric configuration, whose monomerization rate
      constant (k1) is dependent in a bell-shaped manner on the water:surfactant mole
      ratio, w0. A tight correlation between k1 and the double-stranded dimer backbone
      conformation has been found from the comparison of chromatographic and circular
      dichroism data. In addition, fluorescence experiments indicate that the peptide
      tryptophans are in a rather nonpolar environment, with a restricted accessibility
      to water-soluble quenchers such as acrylamide.

PMID- 1380833
TI  - Different patterns of gene expression of topoisomerase II isoforms in
      differentiated tissues during murine development.
AB  - The expression of DNA topoisomerase II alpha and beta genes was studied in murine
      normal tissues. Northern blot analysis using probes specific for the two genes
      showed that the patterns of expression were different among 22 tissues of adult
      mice. Expression levels of topoisomerase II alpha gene were high in proliferating
      tissues, such as bone marrow and spleen, and undetectable or low in 17 other
      tissues. In contrast, high or intermediate expression of topoisomerase II beta
      gene was found in a variety of tissues (15) of adult mice, including those with
      no proliferating cells. Topoisomerase II gene expression was also studied during
      murine development. In whole embryos both genes were expressed at higher levels
      in early than late stages of embryogenesis. Heart, brain and liver of embryos two
      days before delivery, and these same tissues plus lung and thymus of newborn (1
      day-old) mice expressed appreciable levels of the two genes. Interestingly, a
      post-natal induction of the beta gene expression was observed in the brain but
      not in the liver; conversely, the expression of the alpha gene was increased 1
      day after birth in the liver but not in the brain. However, gene expression of a
      proliferation-associated enzyme, thymidylate synthase, was similar in these
      tissues between embryos and newborns. Thus, the two genes were differentially
      regulated in the post-natal period, and a tissue-specific role may be suggested
      for the two isoenzymes in the development of differentiated tissues such as the
      brain and liver. Based on the differential patterns of expression of the two
      isoforms, this analysis indicates that topoisomerase II alpha may be a specific
      marker of cell proliferation, whereas topoisomerase II beta may be implicated in
      functions of DNA metabolism other than replication.

PMID- 1380832
TI  - Human inter-alpha-trypsin inhibitor: full-length cDNA sequence of the heavy chain
      H1.
AB  - Inter-alpha-trypsin inhibitor (ITI), called inter-alpha-inhibitor, is a 220 kDa
      serine proteinase inhibitor found in human serum. It is composed of at least
      three distinct polypeptide chains. These chains, named H1, H2 and L, are an
      independently synthesized and proteolytically processed precursor protein. Only
      the complete structure of H2 and L has been established so far. We used a PCR
      based cloning approach and a cDNA screening library to isolate the full-length
      cDNA H1. The amino acid sequences of the two heavy chains deduced from the cDNA
      are highly similar (40% identity). Nevertheless, the structure of the signal
      peptide and propeptide in the N-terminal region is different in these two chains.
      A complex posttranslational cleavage at both ends of H1 and H2 may be proposed
      prior to assembly of the ITI chains.

PMID- 1380835
TI  - A serine, threonine and proline-rich region near the carboxyl-terminus of a rat
      intestinal mucin peptide.
AB  - Further sequencing of a cDNA encoding the C-terminal region of a rat intestinal
      mucin peptide reveals a region corresponding to 258 amino acids enriched in
      serine, threonine and proline, but no typical mucin-like tandem repeat
      structures. Between this region and a previously described stretch of 4.5
      degenerate S,T,P-rich tandem repeats, there is a 42 amino acid cysteine-rich
      segment. The discontinuity of cysteine-rich and S,T,P-rich areas near the C
      terminus has not been observed in other mammalian mucin structures reported to
      date.

PMID- 1380834
TI  - Molecular cloning of rat glucose-dependent insulinotropic peptide (GIP).
AB  - A cDNA clone encoding glucose-dependent insulinotropic peptide (GIP) was
      identified that consisted of 34 bp of 5' untranslated sequence, an open reading
      frame of 432 bp and 115 bp in the 3' untranslated region. The deduced amino acid
      sequence revealed a 144 amino acid preprohormone consisting of a 43 amino acid N
      terminal extension including a signal peptide, a 42 amino acid hormone, and a 59
      amino acid C-terminal extension. Rat GIP differs from the human hormone by two
      amino acid substitutions: arginine for histidine at position 18 and leucine for
      isoleucine at position 40. A single mRNA from small intestine of approximately
      800 bases was identified on Northern blot analysis in equivalent amounts in
      proximal and distal small intestine.

PMID- 1380836
TI  - The primary structure of chicken ribosomal protein L37a.
AB  - The amino acid sequence of chicken ribosomal protein L37a was deduced from the
      nucleotide sequence of a recombinant cDNA and its genomic DNA. Chicken ribosomal
      protein L37a has 92 amino acids and a molecular mass of 10,247 Da including the
      initiator methionine. The protein contains a typical Cys2Cys2 zinc finger motif,
      which may be involved in protein-RNA interaction.

PMID- 1380837
TI  - Supportive care of neurologic complications.
AB  - Approximately one cancer patient in five will suffer from injuries to either the
      central or peripheral nervous system. These complications occur preferentially in
      the advanced stages of neoplastic disease, and their management is an important
      aspect of the supportive care of these patients. The most common neurologic
      complications seen in patients with cancer are related to metastases or to local
      tumor spread. Antineoplastic treatments, mainly chemotherapy or radiotherapy,
      account for more than 10% of these complications. A much smaller percentage
      (probably less than 1%) are paraneoplastic manifestations. In this review, we
      discuss the most recent developments in the management of neurologic
      complications specifically related to cancer as well as some less specific
      problems such as thromboembolic complications and the use of steroids.

PMID- 1380838
TI  - Kaposi's sarcoma.
AB  - In the era before the acquired immunodeficiency syndrome, Kaposi's sarcoma was a
      rare cutaneous event. Most reported cases usually originated from one of two
      geographic regions, an induced immunosuppressed state, or sporadically with
      various neoplasms that have been known to cause immunosuppression. Since the
      first cases described with acquired immunodeficiency syndrome in 1981 from New
      York and San Francisco, this uncommon disorder has had an increased incidence
      that crosses geographic boundaries. This article describes the current
      understanding of the pathogenesis of Kaposi's sarcoma and treatments used to
      ameliorate this disorder.

PMID- 1380839
TI  - Current strategies for the treatment of hepatocellular carcinoma.
AB  - Although hepatic resection for hepatocellular carcinoma is the only known
      modality that offers an opportunity for cure, the practicing oncologist must be
      aware of alternative modes of therapy. A multidisciplinary approach between
      surgeon, medical oncologist, and invasive radiologist is necessary in exploring
      all potential therapeutic options. The oncologist must not only consider the
      stage of the tumor, but must also take into account the functional reserve of the
      nontumor-bearing liver in selecting appropriate therapy. More recently, hepatic
      transplantation has been recognized as a potential curative modality for specific
      tumor types and stages. Percutaneous ethanol injection and chemoembolization are
      excellent palliative measures. However, it remains clear that new and innovative
      techniques are necessary in the therapeutic, adjuvant, and palliative settings in
      the comprehensive care of the patient with hepatocellular carcinoma.

PMID- 1380840
TI  - CAPD and pancreatitis: no connection.
AB  - Autopsy studies have shown that approximately 56% of patients on long-term
      continuous ambulatory peritoneal dialysis (CAPD) develop various pancreatic
      abnormalities, such as acute and chronic pancreatitis, fibrosis, and acinar
      dilatation. This prevalence of anatomical abnormalities is similar to that
      observed in patients on hemodialysis and higher than that in those with normal
      renal function. However, clinical acute pancreatitis is an uncommon complication
      of CAPD (0.9%), and this prevalence is similar to that (1.7%) of patients on
      hemodialysis. We can attribute acute pancreatitis in CAPD patients to no single
      factor. Perhaps preexisting anatomical abnormalities of the pancreas make the
      CAPD patient susceptible to acute pancreatitis when exposed to a variety of
      physiological and nonphysiological influences. The diagnosis of acute
      pancreatitis in CAPD patients is difficult, because symptoms and signs are
      similar to those of dialysis-associated peritonitis. Serum amylase values three
      times greater than the upper limit of normal and effluent amylase greater than
      100 U/L suggest the diagnosis of acute pancreatitis. Serum lipase, isoamylase,
      and pancreatic secretory trypsin inhibitor are not helpful. In confirming the
      diagnosis, a computed tomography (CT) scan is more helpful than ultrasound,
      although it is positive in only 50-60% of cases. One should harbor a high index
      of suspicion concerning acute pancreatitis if a CAPD patient presenting with
      suspected peritonitis has either a negative effluent culture or does not respond
      to antibiotic therapy.

PMID- 1380841
TI  - Distribution of proline-specific aminopeptidases in human tissues and body
      fluids.
AB  - The proline-specific peptidases, aminopeptidase P (EC 3.4.11.9) and dipeptidyl
      peptidase IV (EC 3.4.14.5), were measured in human tissue homogenates and
      physiological fluids. All tissues examined contained measurable aminopeptidase P
      and dipeptidyl peptidase IV activities. High specific activities for both enzymes
      under study were found in benign prostatic hypertrophy. Normal prostate and
      prostatic adenocarcinoma had a much lower activity. This difference, however, is
      not reflected in the serum values of the patients. The most striking finding is
      the extremely high activity of dipeptidyl peptidase IV in prostatosomes, prostate
      derived organelles, which occur freely in human seminal plasma, and which are
      important for enhancement of sperm forward motility.

PMID- 1380843
TI  - Increased plasma decay-accelerating factor levels in paroxysmal nocturnal
      hemoglobinuria.
AB  - Decay-accelerating factor (DAF) is a complement regulatory membrane protein that
      is often absent from the cell surface of blood cells in paroxysmal nocturnal
      hemoglobinuria (PNH). DAF has also recently been found in the body fluids of
      healthy individuals. However, its precise structure and biological significance
      are not yet clear. To clarify the clinical and pathological implications of free
      DAF, we measured plasma DAF levels in PNH patients, using a newly developed
      quantitative enzyme-linked immunosorbent assay (ELISA), with a measurable range
      between 0.2-12 ng, for soluble DAF. ELISA assays revealed significantly increased
      plasma DAF levels in PNH patients (258 +/- 150 ng/ml, mean +/- S.D., n = 9) as
      compared with healthy controls (80 +/- 41 ng/ml, n = 17) (p less than 0.01).
      Taken together with the finding that DAF is synthesized in and released
      extracellularly from affected PNH cells, plasma DAF levels would be useful for
      clinical diagnosis and for the quantitative evaluation of the clonal expansion of
      affected cells in PNH.

PMID- 1380842
TI  - Effect of progestin, antiprogestin, and relaxin on the accumulation of prolactin
      and insulin-like growth factor-binding protein-1 messenger ribonucleic acid in
      human endometrial stromal cells.
AB  - Prolactin (PRL) and insulin-like growth factor-binding protein (IGFBP-1) are two
      major secretory proteins of human endometrial/decidual cells. We have
      characterized the mRNA of PRL and IGFBP-1 and studied the effect of progestin,
      medroxyprogesterone acetate (MPA), anti-progestin (RU486), and relaxin (RLX) on
      the levels of these two mRNA transcripts in a long-term culture of human
      endometrial stromal cells. Northern blot analysis showed that the size of PRL
      mRNA was 1.15 kb and that of IGFBP-1 mRNA, 1.6 kb. Primer extension of
      endometrial/decidual IGFBP-1 mRNA showed two transcription initiation sites
      identical to those found in HepG2 human hepatoma cell line. The levels of mRNA in
      control samples remained low, approximately 2 pg PRL and approximately 5 pg IGFBP
      1/microgram RNA at various times of culture. When stromal cells were treated with
      MPA for 28 days, PRL mRNA gradually increased 100-fold whereas IGFBP-1 mRNA
      exponentially increased approximately 1000-fold compared to control values and
      leveled after 25 days in culture. The timing of maximal stimulation was shortened
      by withdrawing MPA or by replacing MPA with RU486. After removal of MPA, levels
      of both mRNAs increased and each peaked after approximately 10 days, with PRL
      showing a 2-fold and IGFBP-1 a 20-fold increase compared to cells treated with
      MPA continuously. Replacing MPA by RU486 caused a rapid increase of PRL mRNA (2-3
      fold) in 2-3 days followed by a gradual reduction to less than 20% of peak levels
      over the next 3 days. IGFBP-1 mRNA levels increased 30- and 100-fold in 1-2 days
      followed by a reduction to less than 20% of peak levels over the next 24 h. The
      reduction of mRNA levels by RU486 was reversed when cells were rechallenged with
      MPA. Relaxin alone caused a transient stimulation of PRL and IGFBP-1 mRNA.
      Maximal stimulation occurred between 10 and 20 days of culture and was 100-fold
      for PRL and 1000-fold for IGFBP-1 relative to control values. Cells treated with
      MPA and RLX in sequence had higher mRNA levels than cells treated with MPA
      continuously or cells subjected to MPA withdrawal. Maximal mRNA levels reached
      0.4 ng PRL and approximately 8 ng IGFBP-1/microgram total RNA, approximately
      0.04% and 0.8% of cellular RNA. The mRNA levels under various hormonal
      manipulations were similar to the previously published synthesis and secretion
      patterns of PRL and IGFBP-1 proteins in this system.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1380844
TI  - Interleukin-3 and granulocyte colony-stimulating factor as survival factors in
      murine hemopoietic stem cells in vitro.
AB  - We examined the role of various hemopoietic factors in the survival of
      hemopoietic stem cells in methylcellulose culture. Bone marrow cells from 5
      fluorouracil (5-FU)-treated mice were cultured without hemopoietic factors.
      Several days later, a mixture of colony-stimulating factors (CSF interleukin-3
      (IL-3), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and
      erythropoietin (Ep)) was added to the culture (delayed addition of CSF) to induce
      the maximal colony growth in surviving progenitors. In this system few colonies
      grew, suggesting that some hemopoietic factors are required for the survival of
      hemopoietic stem cells in vitro. In a further series of experiments, similar
      cultures were initiated with single known hemopoietic factors or with a mixture
      of CSF, followed by the addition of CSF 7 days later. Although IL-3 and G-CSF, as
      single factors, supported colony growth, the other factors did not. In this
      experiment, while the total number of colonies in cultures initiated with IL-3 or
      G-CSF was less than that observed in cultures initiated with a mixture of CSF,
      the number of multipotential GEMM (granulocyte-erythrocyte-macrophage
      megakaryocyte) colonies remained constant. We concluded that IL-3 and G-CSF
      played important roles as single factors in the survival of murine dormant
      hemopoietic stem cells in vitro.

PMID- 1380845
TI  - Colocalization of thrombospondin and syndecan during murine development.
AB  - Thrombospondin is an adhesive glycoprotein that is thought to play a role in
      tissue genesis and repair. We have used a monoclonal anti-thrombospondin
      antibody, designated 5G11, to localize thrombospondin in paraformaldehyde fixed,
      paraffin-embedded sections of developing mouse embryos. Thrombospondin expression
      is observed in uterine smooth muscle, endometrial glands, the decidua, and
      trophoblastic giant cells during the initial phase of post-implantation
      development in the embryo. Cardiac myocytes and neuroepithelial cells show
      positive staining for thrombospondin at day 8.5 of gestation, and this expression
      continues throughout the development of the myocardium and central nervous
      system. Strong staining for thrombospondin is seen in developing bone and in the
      liver. Thrombospondin is also observed in developing smooth muscle and skeletal
      muscle, as well as in a variety of epithelia, including the epidermis, small
      intestinal epithelium, lens epithelium, renal tubular epithelium, and the
      epithelium of the developing tooth. Comparison of thrombospondin staining with
      that of two known cell surface receptors for thrombospondin, syndecan and the
      vitronectin receptor, reveals remarkable colocalization of thrombospondin and
      syndecan in all tissues, but almost no coexpression with the vitronectin
      receptor. Coexpression of thrombospondin and syndecan may play an important role
      in cell-cell or cell-matrix interactions during development.

PMID- 1380846
TI  - Histochemical localization of Statin--a non-proliferation-specific nuclear
      protein--in nuclei of normal and abnormal human thyroid tissue.
AB  - Surgical specimens of 29 human thyroid masses, both benign and malignant, were
      examined by means of a novel monoclonal antibody immunoreactive to statin, which
      is expressed only in quiescent G0 cells. The nuclei of normal thyroid follicle
      tissue together with nodular goitres and follicular adenomata had similar
      labelling indices of 96 +/- 2.67, 95 +/- 2.43 and 94 +/- 1.98 respectively. By
      contrast the labelling indices of papillary and undifferentiated thyroid
      malignancies were 82 +/- 3.05 and 15.2, respectively. These results indicate that
      normal thyroid tissues as well as benign thyroid tumors have similar non
      proliferative activities. The differentiated papillary cancers have a smaller non
      cycling compartment, the smallest being present in the most biologically
      aggressive undifferentiated thyroid cancer. The immunohistological evaluation of
      statin in the nuclei of human thyroid malignancies correlates with their
      biological behaviour in an inverse relationship.

PMID- 1380847
TI  - Study of infection by human papillomavirus in severe dysplasias and carcinomas in
      situ of the uterine cervix using immunohistochemistry and in situ hybridization.
AB  - Diagnosis of human papillomavirus (HPV) infection in uterine cervical lesions is
      usually based on histopathological criteria and, in some cases, is confirmed by
      immunohistochemistry. The recent development of in situ hybridization techniques
      has facilitated the detection of HPV in these lesions. Consequently, we carried
      out a study on 18 uterine cervical biopsy specimens histopathologically diagnosed
      as severe dysplasias and carcinomas in situ, using an immunohistochemical method
      with a rabbit polyclonal antibody against the HPV common structural antigen and
      in situ hybridization techniques with three biotinylated DNA probes for HPV types
      6/11, 16/18, and 31/35/51. By immunohistochemistry only one case (5.5%) proved to
      be positive, whereas by in situ hybridization 12 HPV-positive cases were obtained
      (66.6%), of which 7 were positive for HPV types 16/18 (38.8%) and 6 for HPV types
      31/35/51 (33.3%). One case was positive with positive with both DNA probes. From
      our results it can be inferred that in situ hybridization is a more sensitive
      technique than immunohistochemistry for confirming the presence of HPV in severe
      dysplasias and carcinomas in situ of the uterine cervix. Furthermore, in situ
      hybridization provides much more information than immunohistochemistry since it
      permits the identification of the HPV types causing the lesion.

PMID- 1380848
TI  - Staining reaction for beta-galactosidase in immunocytochemistry and in situ
      hybridization.
AB  - beta-galactosidase, revealed by an indigo blue reaction product, represents a
      valid tracer in immunohistochemistry. Observations on the instability of the
      indigo precipitate led us to investigate this phenomenon. We conclude that
      avoiding of xylene, and mounting of the preparates in Histoclear (a xylene
      substitute) and Canada balsam (instead of synthetic resin mountants) yields a
      sharp and stable indigo precipitate. In addition, we propose a sensitive
      alternative staining procedure for beta-galactosidase, based on TNBT reduction
      and precipitation. These reactions can be used both in immunohistochemistry and
      in in situ hybridization.

PMID- 1380849
TI  - Morphological and histochemical study of supragingival human calculus and dental
      plaque using ruthenium hexammine trichloride and acridine orange.
AB  - Ruthenium hexammine trichloride (RHT) and acridine orange were used to preserve
      and visualize anionic groups in human plaque and dental calculus. RHT-reacting
      material was present on the membrane of micro-organisms and in intermicrobial
      spaces of the calcifying areas, and seems to correspond to, and derive from,
      acidic glyco- and phospholipids of the plasma membrane of the micro-organisms.
      However, the presence of acidic salivary peptidoglycans cannot be ruled out. Two
      types of calcification were found: extramicrobial and intramicrobial. The former
      consisted of calcified deposits irregularly scattered in the intermicrobial
      matrix. They were in close relationship with RHT-reacting material, or were
      placed inside vesicular structures delimited by a membrane. Intramicrobial
      calcification consisted of small aggregates of needle-shaped crystals and/or of
      granular deposits; in both cases, they either masked the whole cytoplasm of the
      micro-organisms, or were located only over the plasma membrane. These results
      suggest that mineral deposition occurs in connection with acidic components of
      intermicrobial matrix, microbial plasma membranes, and cytoplasms. The addition
      of RHT and acridine orange to fixing and decalcifying solutions yields
      satisfactory preservation of dental calculus and plaque, and apparently reduces
      loss of their anionic organic components and increases their electron density.
      However, these substances are not sufficient to preserve all ultrastructural
      details in decalcified areas, probably because the inorganic substance prevents
      reaction of acridine orange and RHT with the organic components of the calcified
      matrix.

PMID- 1380851
TI  - Recurrent chromosome alterations in transitional cell bladder carcinomas.
AB  - A karyotype study was performed in 42 cases of transitional cell bladder
      carcinoma. The results, confirmed by DNA content evaluation, showed a prevalence
      of near-diploid modes not related to the histologic grade of differentiation.
      Nonrandom alterations were represented by monosomy of chromosome 13 and 22,
      trisomy of chromosome 7 and deletion of chromosomes 6 and 11. These anomalies
      allow the identification of different sub-groups of tumors, each with its own
      biological characteristics of aggressiveness. Prognosis was particularly poor in
      cases with monosomy of chromosomes 13 and 22 but more favourable in poorly
      differentiated carcinomas with trisomy of chromosome 7.

PMID- 1380850
TI  - Importance of acidic mucin secretions by foveolar and mucous neck cells of rat
      fundic mucosa as the defence mechanisms against HCl as revealed by fasting.
AB  - The localization of neutral mucin and acidic mucins in both control and fasted
      rat gastric fundic mucosa were examined by microscopic and electron microscopic
      histochemical methods. By Carnoy's fixation, the surface mucous coat of the
      control rat gastric fundic mucosa was found to be composed of alternating layers
      of acidic mucins and neutral mucin, indicating the synchronous and cyclic
      secretions of them. In many gastric pits of the fundic glands, the acidic mucins
      were found to spring out from the deep foveolar regions like volcanoes. This
      phenomenon may suggest that the acidic mucins play a fundamental role in
      protecting the pit cells against HCl during its passage, and the layers of
      neutral mucin and acidic mucins in the surface coat is the safeguard against the
      HCl and digestive enzymes in the gastric lumen. In the fasting rat gastric fundic
      mucosa, the acidity and the amount of the gastric juice were markedly decreased,
      indicating the suppressed secretions of mucins and HCl. The decreased production
      of sulfomucin was directly demonstrated by 35SO4-autoradiography. Many mucous
      neck cells existing in close association with the parietal cells were ballooned
      due to accumulation of alcian blue (AB)-positive but high iron-diamine (HID)
      negative sialomucin, which was not demonstrable in the control. The secretory
      granules of sialomucin contained in the ballooned mucous neck cells were
      positively stained ultrastructurally with cacodylate-ferric colloid to stain acid
      mucopolysaccharides.

PMID- 1380852
TI  - Mallory stain may indicate differential rates of RNA synthesis: II. Comparative
      observations in vertebrate nuclei.
AB  - The differential staining of nuclei by the use of the Mallory trichrome method
      was investigated in a variety of tissues of representative vertebrates. By this
      method nuclei stained orange or blue; erythrocyte nuclei stained red. Since the
      higher affinity for aniline blue is due to an increased RNA synthesis, it was
      possible to reveal not only the changing metabolic status of a cell type, as
      shown for instance in the liver parenchyma and other glandular tissues, and
      nervous tissue, but also in different cell populations in the same tissue, such
      as the spleen.

PMID- 1380853
TI  - Electron spectroscopic imaging and X-ray microanalysis of phosphorus in mouse
      sperm chromatin.
AB  - The influence of HCl hydrolysis on DNA detection in a Feulgen-type reaction using
      osmium ammine has been analyzed at the electron microscopic level by means of
      electron spectroscopic imaging, electron energy loss spectroscopy and X-ray
      microanalysis in energy dispersive spectroscopy. Both the stained DNA and the
      phosphorus mapping for a given hydrolysis condition were studied in parallel on
      the same nucleus. We have found that the pattern of osmium ammine-stained DNA and
      phosphorus imaging can be superimposed for a short hydrolysis time. After long
      HCl treatment, DNA is barely detectable by osmium ammine while phosphorus is
      still present in the thin sections. Taking into account the fact that the cells
      are embedded in a plastic resin, it is reasonable to think that in this case DNA
      depolymerization does not completely correspond to DNA loss. An incomplete loss
      of this highly denatured and depolymerized DNA from the plastic sections will
      explain both the presence of phosphorus and the poor stainability with a Schiff
      type reagent.

PMID- 1380854
TI  - Immunocytochemical detection of dendritic cell by S-100 protein in the chicken.
AB  - Positivity for S-100 protein in paraffin embedded chicken lymphoid tissue was
      found by using a polyclonal antibody against whole bovine S-100 protein. The S
      100 protein-containing cells were observed in the locations which have been
      reported to contain avian dendritic cells such as the medulla of the bursal
      follicles, and the germinal centers and T-dependent areas in the spleen, Peyer's
      patches, caecal tonsil and Harderian gland. Positive cells were also found in the
      location where ellipsoid associated cell have been described, and between
      epithelial cells covering the Peyer's patches and the caecal tonsil, as well as
      between the cells lining the ducts within the Harderian gland. Macrophages were
      devoid of immunostaining. Our results confirm the location described elsewhere
      for chicken dendritic cells and indicate that S-100 protein can be considered as
      a cell marker for the identification of the chicken dendritic cell.
      Intraepithelial positive cells may be interdigitating dendritic cells in an
      unusual location (their function being the transport of the antigen from the
      epithelium to the diffuse lymphoid tissue), or cytotoxic T-lymphocytes which, in
      mammals, are immunoreactive for S-100 protein.

PMID- 1380855
TI  - A histochemical study of the microglial cells in the brain of Salamandra
      salamandra by lectin binding.
AB  - Seven biotinylated lectins were utilized as histochemical markers for the study
      of microglial cells in the brain of Salamandra salamandra. It has been
      demonstrated that SBA, BSA-I, BSA-I-B4 and RCA120 label the microglial cells and,
      on the basis of the binding selectivity of the single lectins for specific
      carbohydrates, it was found that alpha-galactosyl residues are present in high
      density on the microglial membrane of S. salamandra. The reaction was localized
      not only to the ramified microglial cells, but also to other round cells without
      extensions, interpreted as ameboid microglial cells. The results show that lectin
      binding is a reliable molecular probe for identifying microglial cells in
      urodels.

PMID- 1380857
TI  - Acid phosphatase activity in the supramedullary neurons of Coris julis (L.).
AB  - This work describes the acid phosphatase activity in supramedullary neurons of
      Coris julis, analyzed by a cytochemical method. The presence of both acid
      phosphatase-positive and -negative membrane bound granules indicates that only a
      part of the numerous electrodense granules in the supramedullary neurons can be
      interpreted as lysosomes. The great number of lysosomes in these large neurons of
      young animals is indicative of the rapid turnover of cell structures, which may
      be correlated with the high rate of synthesis. The electrodense granules showing
      no acid phosphatase activity are postulated to be vesicles containing gastrin/CCK
      like peptide or precursors of this neuromediator.

PMID- 1380856
TI  - Comparative histopathological alterations in the digestive gland of marine
      bivalves exposed to Cu and Cd.
AB  - This study compares the histopathological alterations in the digestive gland
      cells of mussels, Mytilus galloprovincialis and clams, Ruditapes phillipinarum
      following exposure to copper and cadmium. The results show degenerative processes
      undergone in the digestive gland ranging from inflammatory responses to extreme
      vacuolation, particularly in Cd-exposed individuals. Unsaturated neutral lipids
      tend to accumulate in pathologically enlarged lysosomes of the homogeneous-type
      or heterogeneous-type depending of the species and of metal. Lipofucsins
      containing granules were mainly found in Cu-exposed mussels and Cd-exposed clams.
      No granules were detected in Cd-mussels. The comparison of the methods indicate
      that paraffin sections are also a suitable material for the localization of
      lipofucsins.

PMID- 1380858
TI  - A light-microscopic immunocytochemical study of the endocrine pancreas in the
      Australian brush-tailed possum (Trichosurus vulpecula).
AB  - The endocrine pancreas of the Australian brush-tailed possum (Trichosurus
      vulpecula) was investigated by means of immunocytochemistry using the avidin
      biotin-peroxidase technique. This was a light microscopic study using this
      established technique. Serial paraffin sections were stained individually with
      primary antibodies for glucagon, insulin, somatostatin, and pancreatic
      polypeptide (PP), showing the same islet. Cells immunoreactive to glucagon,
      insulin, somatostatin and PP were found in endocrine islets. PP cells appear to
      be scattered amidst the exocrine portion also. Insulin immunoreactive cells were
      located in the central region of islet, glucagon in the periphery, somatostatin
      in periphery and had elongated processes. PP cells were more sparse and located
      both in the periphery of islet and amidst the exocrine tissue. These results can
      then be related to a similar study in the same marsupial, but using the
      immunofluorescence technique and to studies in other marsupials such as grey
      kangaroo (Macropus fuliginosus) fat-tailed dunnart (Sminthopsis crasicaudata) and
      the American opossum (Didelphis virginiana). These investigations are part of a
      study in Australian mammals.

PMID- 1380859
TI  - Correction of emission spectra in microspectrofluorimetry using a reference lamp:
      computations.
AB  - Accurate correction of emission spectra in microspectrofluorimetry, using a
      reference lamp, may require that a factor for the emissivity of tungsten be
      introduced. This is only possible provided that the true temperature of the lamp
      filament is known. A method is given for obtaining the true temperature from the
      knowledge of the colour temperature. Also, the values of the spectral
      concentration of the radiance of the black body, either computed according to
      Planck's equation or taken from available published tables, have to be converted
      from energetic units to units of quanta since the photomultiplier is linear not
      to absorbed power but to units of quanta. When the fluorescence spectra to be
      corrected extend into the far red it is preferable to use a lower temperature (by
      lowering the supply voltage) than that for which the lamp is certified. It is
      possible to determine the new temperature (and then the corresponding spectral
      distribution) by taking a few pairs of measurements at different wavelengths both
      at the lower voltage and at the voltage for which the lamp is certified and then
      introducing these values in a non-linear regression soluble on a PC with a curve
      fitting program. The microscope tungsten halogen lamp can conveniently be used as
      a reference, thanks to its small size and its steady spectral characteristics.
      When high accuracy is required, however, the halogen lamp should be calibrated
      against a certified ribbon filament lamp.

PMID- 1380860
TI  - Neonatal plasma concentrations of secretory leucocyte protease inhibitor.

PMID- 1380861
TI  - Neurochemical predisposition to self-administer morphine in rats.
AB  - Using in vivo microdialysis, this study attempted to determine whether a
      neurochemical predisposition to self-administer morphine could be identified.
      Extracellular levels of dopamine and its metabolites were measured bilaterally in
      the mesocorticolimbic and nigrostriatal systems of naive rats that were
      subsequently trained to self-administer morphine intravenously. There were
      several significant relationships between dopamine metabolite 3,4
      dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and rates
      of morphine self-administration during both acquisition and asymptotic phases of
      testing. DOPAC and HVA levels in the striatum were inversely correlated with self
      administration rates during the asymptotic phase whereas hemispheric asymmetries
      in striatal metabolite levels were inversely correlated with self-administration
      during the acquisition phase. DOPAC and HVA levels in in the right but not in the
      left side of the medial prefrontal cortex were positively correlated with self
      administration rates during the acquisition phase; right/left asymmetries in
      cortical metabolite levels were also correlated with acquisition rates. There
      were no significant relationships between neurochemical indices and rates of bar
      pressing for water. These results suggest that the normal variability in drug
      seeking behavior is at least in part attributable to individual differences in
      the organization and activity of brain dopamine systems. Furthermore, different
      mechanisms appear to be responsible for the initiation and maintenance of
      morphine intake: DA release in the nucleus accumbens appears to be a critical
      component of both mechanisms; DA release in the striatum appears to modulate
      maintenance and, in relationship to striatal lateralization, modulate initiation;
      DA release in the right but not in the left medial prefrontal cortex appears to
      be an important predictor of initiation.

PMID- 1380862
TI  - Effects of repeated injections of cocaine on catecholamine receptor binding
      sites, dopamine transporter binding sites and behavior in rhesus monkey.
AB  - In order to determine if repeated injections of cocaine produced long-lasting
      alterations in catecholaminergic binding sites, rhesus monkeys were treated with
      saline (1.0 ml/15 kg) or cocaine (3.0-4.0 mg/kg) four times daily for 14
      consecutive days and sacrificed two weeks after the last injection. The densities
      of dopamine D1 receptor binding sites, dopamine transporter binding sites and
      beta adrenergic receptor binding sites were significantly decreased in caudate
      nucleus to 51%, 17% and 61% of control, respectively, two weeks after repeated
      cocaine injections. There were no differences in D2 receptor binding site
      densities in the caudate, nor were there differences in binding sites between
      groups in the other brain regions examined: prefrontal cortex (D1, D2, dopamine
      transporter, beta), nucleus accumbens (D1, D2, dopamine transporter) and
      substantia nigra (D2). Behavioral observation showed that the cocaine-treated
      monkeys became sensitized to the repeated injections. Early in the regimen, these
      animals displayed stereotypic grooming, buccal movements and visual checking
      after each injection that differed significantly from the saline-treated animals.
      As the regimen progressed, the frequency of grooming decreased while the
      frequencies of visual tracking and splayed legs increased in a manner consistent
      with the development of behavioral sensitization. Together, these findings
      suggest that the caudate nucleus may be more sensitive than other dopamine
      containing brain regions to long-lasting pre- and post-synaptic effects of
      repeated cocaine administration, and that the changes seen in dopaminergic
      neurons may be related to behavioral sensitization.

PMID- 1380864
TI  - The anatomical evidence of recurrent axonal collaterals of the thalamus
      projecting neurons of the rostral pole of the trigeminal sensory nuclear complex
      in the rat.
AB  - Thalamus projecting neurons and their recurrent axonal collaterals were observed
      in the dorsomedial part of the trigeminal principal sensory nucleus (Vpdm) and
      the caudolateral part of supratrigeminal nucleus (Vsup CL) after injection of
      horseradish peroxidase (HRP) into the contralateral ventrobasal complex of the
      thalamus (VBm) by using the HRP retrogradely tracing-Golgi-like staining method.
      About 7% (8/120) parent axons of the labeled cells gave rise to recurrent axon
      collaterals. However, no retrogradely labeled cells were observed in the VBm
      after injection of HRP into the Vpdm and Vsup CL. In an electron microscopic
      study, the terminals of recurrent axon collaterals made synapses with the
      dendrites of the thalamus projecting neurons or non-labeled neurons in the
      neuropil of the Vpdm and Vsup CL. It is suggested that the recurrent axon
      collaterals might play a role of negative feedback in transmission of the
      proprioceptive message from the jaw-closing muscle spindles to the thalamus.

PMID- 1380863
TI  - Chloride current induced by alcohols in rat dorsal root ganglion neurons.
AB  - We have recently demonstrated that ethanol and longer-chain alcohols (n-alcohols)
      enhance gamma-aminobutyric acid (GABA)-induced chloride currents before
      desensitization takes place. The potencies of n-alcohols increase with
      lengthening of the carbon chain. We now report that n-alcohols induce chloride
      currents by themselves in rat dorsal root ganglion neurons in primary culture.
      The whole cell variation of the patch clamp techniques was used to record
      currents as induced by external application of alcohols and other test compounds.
      Ethanol, n-butanol, n-hexanol and n-octanol induced inward currents with their
      potencies increasing in that order. The potencies were approximately one order of
      magnitude less than those to augment GABA-induced currents. The maximum
      amplitudes of currents induced by the alcohols were less than those produced by
      GABA. The n-octanol-induced currents were carried largely by chloride ions
      because the reversal potentials were changed according to the Nernst chloride
      potential as the internal chloride concentration was changed. Bicuculline and
      picrotoxin suppressed the n-octanol-induced current, and chlordiazepoxide and
      pentobarbital augmented the n-octanol-induced current. Therefore, the alcohol
      induced chloride currents flow through the chloride channels associated with the
      GABAA receptors. When applied after the GABA-induced current was desensitized to
      a lower level, n-octanol suppressed rather than augmented the current. Thus, n
      alcohols mimic barbiturates in augmenting the GABA-induced currents and in
      generating chloride currents by themselves. These actions of both agents may play
      a role in causing anxiolytic, sedative and/or anesthetic effects.

PMID- 1380866
TI  - Modulation of dye coupling among glial cells in the myenteric and submucosal
      plexuses of the guinea pig.
AB  - Dye coupling among glial cells in the ganglia of the myenteric and submucosal
      plexuses of the guinea-pig ileum was studied by intracellular injection of the
      dye Lucifer yellow (LY), which crosses gap junctions. The injection of a single
      glial cell with LY resulted in the staining of many glia. The mean number of
      cells coupled to the injected one was 87.0 +/- 7.9 in the myenteric plexus, and
      20.7 +/- 5.6 in the submucosal plexus. As previously shown for myenteric plexus,
      injection of horseradish peroxidase into submucosal glia resulted in the staining
      of only a single cell. Dye coupling was significantly reduced in both plexuses by
      lowering intracellular pH, by replacing 100 mM of the chloride ions with
      propionate ions or by bubbling the solution with 100% CO2. Octanol (0.3 mM) also
      markedly diminished dye coupling in the two preparations. These treatments are
      known to block gap junctions in a variety of tissues. It is concluded that, like
      central glial cells, enteric glia are extensively coupled. This coupling is
      apparently mediated by gap junctions.

PMID- 1380865
TI  - Tyrosine hydroxylase-, neurotensin-, or cholecystokinin-containing neurons in the
      nucleus tractus solitarii send projection fibers to the nucleus accumbens in the
      rat.
AB  - A double-labeling method combining the retrograde tracing of horseradish
      peroxidase (HRP) with the immunocytochemical technique was used in the present
      study. The results suggest that the neurons containing tyrosine hydroxylase (TH),
      neurotensin (NT) or cholecystokinin (CCK) in the nucleus tractus solitarii (NTS)
      of the rat send their axons to the nucleus accumbens bilaterally with ipsilateral
      dominance. HRP-TH, HRP-NT or HRP-CCK double-labeled cell bodies were mainly
      located in the medial and the commissural subnucleus of the NTS. HRP-TH double
      labeled cells were the largest in number, followed by HRP-NT cells, with HRP-CCK
      cells present in the lowest numbers.

PMID- 1380867
TI  - Chronic MPTP treatment reduces substance P and met-enkephalin content in the
      basal ganglia of the marmoset.
AB  - Common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP, 1.25-2.5 mg/kg s.c., twice a week) for 5-10 consecutive months. The
      initial doses of MPTP produced a severe parkinsonian syndrome but motor activity
      was partially recovered at the end of treatment. Fifteen days or 6 months after
      the last MPTP dose, monkeys were sacrificed. In addition to a strong decrease of
      dopamine in the striatum, there were significant reductions in substance P and
      Met-enkephalin content in the substantia nigra, caudate nucleus and putamen. In
      the globus pallidus, the reduction in peptide levels did not reach statistical
      significance as compared to controls. Neurotensin levels were also decreased in
      the caudate nucleus. The chronic administration of MPTP for 5-10 months induces
      changes in substance P and Met-enkephalin systems which resemble the degeneration
      found in brains from parkinsonian patients.

PMID- 1380868
TI  - Immunohistochemical localization of nerve growth factor in the rat pineal gland.
AB  - Sympathetic nerve fibers arising from the superior cervical ganglia are the main
      innervation of the rat pineal gland. Since most organs innervated by these
      ganglia contain nerve growth factor (NGF), the hypothetical existence of NGF in
      the pineal gland was investigated. The peroxidase anti-peroxidase technique was
      applied for the immunohistochemical demonstration of NGF using a polyclonal
      antiserum on Bouin-fixed, paraffin-embedded pineal glands from adult, young and 6
      hydroxydopamine (6-OHDA)-treated rats. Few immunopositive cells were observed in
      the adult pineal gland. A more conspicuous population of immunoreactive cells was
      noted in young animals (20-45 days old), especially in those chemically
      denervated with 6-OHDA. NGF immunoreactive cells displayed a stellate shape
      resembling the interstitial or glial cells previously described in the rat pineal
      gland. Since NGF plays a trophic effect on sympathetic neurons during development
      and adulthood, we postulate that its presence in the pineal gland may exert a
      trophic role on its sympathetic innervation.

PMID- 1380869
TI  - Projection from the deep cerebellar nuclei to the pedunculopontine nucleus in the
      squirrel monkey.
AB  - Large injections of the anterograde tracer biocytin in the deep nuclei of the
      cerebellum of squirrel monkeys (Saimiri sciureus) led to a massive labeling of
      the superior cerebellar peduncle fibers which could be followed up to their major
      termination site in the thalamus. Along their course through the brainstem,
      biocytin-labeled fibers emitted fine collaterals that arborized profusely within
      the entire rostrocaudal extent of the pedunculopontine nucleus (PPN). These
      fibers were long, slightly varicose, and broke off into numerous shorter and
      thinner fibers whose terminal portions consisted of a few large varicosities that
      were often closely apposed to dendrites and cell bodies of PPN neurons. Some PPN
      cells that were contacted displayed immunoreactivity for choline
      acetyltransferase. Ultrastructural analysis revealed that synapses formed by
      cerebellar fibers in PPN were of the asymmetric type and occurred predominantly
      on dendrites of PPN neurons. Thus, beside the well established cerebellothalamic
      projection, our findings reveal the existence of a cerebellotegmental projection,
      whereby the cerebellum may influence the basal ganglia and/or the thalamus via a
      relay in PPN.

PMID- 1380870
TI  - Dynamics of 7B2 and galanin expression in solitary magnocellular hypothalamic
      vasopressin neurons of the homozygous Brattleboro rat.
AB  - The homozygous Brattleboro rat (di/di), displaying a hypothalamic form of
      diabetes insipidus, synthesizes a vasopressin (VP) precursor with an abnormal C
      terminus. The phenotypic expression of coexisting peptides in mutant
      magnocellular VP cells shows a differential pattern. 7B2 is one of the peptides
      which is not detectable, whereas there is a clear galanin expression. During
      postnatal life a small but increasing number of solitary post-mitotic VP neurons
      of the di/di rat undergoes a switch to a heterozygous phenotype. Here we report
      the presence of 7B2 and galanin in these heterozygous cells, which suggests that
      for the expression of 7B2, but not for that of galanin, the relative amount of
      mutant VP precursor must be diminished. Possible underlying mechanisms for this
      differential phenotypic expression of coexisting peptides are
      compartmentalization of precursor synthesis within the RER or a competition for
      sites involved in the translocation of the functionally reduced RER.

PMID- 1380872
TI  - Chondroitin sulfate in the extracellular matrix of the medial and lateral
      superior olivary nuclei in the dog.
AB  - Chondroitin sulfate was examined in the extracellular matrix of the canine medial
      and lateral superior olivary nuclei by light and electron microscopic
      immunocytochemistry. The extracellular matrix around the large neurons was
      intensely stained with a monoclonal antibody recognizing D-glucuronic acid 2
      sulfate----N-acetylgalactosamine 6-sulfate (D-unit) and this staining degree was
      remarkably reduced after chondroitinase ABC digestion. Neuronal cytoplasm, glial
      cells or capillaries in these nuclei were not stained with the monoclonal
      antibody. The results indicate the presence of disaccharide residue of D
      glucuronic acid 2-sulfate----N-acetylgalactosamine 6-sulfate in the chondroitin
      sulfate proteoglycan of the extracellular matrix.

PMID- 1380871
TI  - Identification of a src family protein specifically expressed in rat astrocytes
      by immunohistochemistry and double immunofluorescent study.
AB  - Identification of a src-related tyrosine kinase and its regional and cellular
      distributions were studied in rat brain. The study was performed using a specific
      antibody raised against a synthetic peptide corresponding to the conserved
      autophosphorylation site of src-family tyrosine kinases. The antibody (alpha-src
      antibody) recognized a 43 kDa polypeptide in plasma membrane enriched fraction.
      The immunohistochemical data revealed that the polypeptide is localized in
      astrocytes of corpus callosum and fimbria hippocampus. The presence of this src
      related protein in astrocytes suggests that it may have some control in their
      proliferation and differentiation.

PMID- 1380873
TI  - Intracellular calcium release in N1E-115 neuroblastoma cells is mediated by the
      M1 muscarinic receptor subtype and is antagonized by McN-A-343.
AB  - Experiments using muscarinic receptor antagonists were done to determine which
      muscarinic receptor subtypes(s) mediate carbachol-evoked calcium release in N1E
      115 cells. McN-A-343 and a new analog, (+/-)BN228, were weak antagonists and
      neither compound caused release on its own. The rank order of potency was 4-DAMP
      greater than pirenzepine greater than AFDX116 greater than (+/-)BN228 and McN-A
      343. This profile, pirenzepine's high potency (19-fold greater than AFDX116) and
      its IC50 of 31 nM suggest that calcium release in this neuronal cell line is
      mediated by the M1 muscarinic receptor subtype.

PMID- 1380874
TI  - Non-dopaminergic neurons in the substantia nigra project to the reticular
      formation around the trigeminal motor nucleus in the rat.
AB  - The dorsolateral part of the substantia nigra (SN) of the rat was observed to
      send projection fibers to the reticular formation (RF) around the trigeminal
      motor nucleus (Vm), bilaterally with a clear-cut ipsilateral dominance, by the
      anterograde and retrograde tracing techniques with PHA-L and WGA-HRP. A
      combination of retrograde tracing and immunohistochemistry for tyrosine
      hydroxylase (TH) revealed that no SN neurons sending their axons to the RF around
      the Vm showed TH-like immunoreactivity.

PMID- 1380875
TI  - Post-train administration of 9-amino-1,2,3,4-tetrahydroacridine enhances passive
      avoidance retention and decreases beta-adrenoceptor-linked cyclic AMP formation
      in middle-aged rats.
AB  - The possible involvement of beta-adrenoceptor system in the effectiveness of 9
      amino-1,2,3,4-tetrahydroacridine (THA) to attenuate retention deficits exhibited
      by middle-aged rats in a one-trial passive avoidance task has been investigated.
      THA (2.5 mg.kg-1), injected i.p. after training, induced a significant increase
      in test step-through latency (STL) in middle-aged rats. Post-training injection
      of THA reduced basal and isoprenaline stimulated cyclic AMP accumulation in
      cortex and hippocampus of every group of rats. It is suggested that the effect of
      THA on memory processes may involve an action on beta-adrenoceptor-linked cyclic
      AMP accumulation.

PMID- 1380876
TI  - Protection of rat hippocampus against ischemic neuronal damage by pretreatment
      with sublethal ischemia.
AB  - We examined whether preconditioning with sublethal ischemia protects against
      neuronal damage following subsequent lethal ischemic insults. Forebrain ischemia
      for 3 min in Wistar rats increased heat shock protein-70 immunoreactivity in the
      hippocampal CA1 subfield but produced no neuronal damage. Preconditioning with 3
      min of ischemia followed by 3 days of reperfusion protected against hippocampal
      CA1 neuronal damage following 6 and 8 min of ischemia but not damage after 10 min
      of ischemia. The result strongly suggests that stress response induced by
      sublethal ischemia protects against ischemic brain damage.

PMID- 1380877
TI  - 1,9-Dideoxyforskolin does not mimic all cAMP and protein kinase A independent
      effects of forskolin on GABA activated ion currents in adult rat sensory neurons.
AB  - The effect of forskolin on GABAA receptor activated events has been the subject
      of recent investigations, the conclusions of which are conflicting. Forskolin can
      reduce current amplitude and increase the rate of decay of current activated by
      100 microM GABA and these effects are not mimicked by 1,9-dideoxyforskolin
      (Tehrani et al., Synapse, 4 (1989) 126-131). On the other hand, both forskolin
      and 1,9-dideoxyforskolin inhibit 36Cl- flux induced by lower concentrations of
      muscimol (Heuschneider and Schwartz, Proc. Natl. Acad. Sci. USA, 86 (1989) 2938
      2942). Using the whole-cell patch clamp technique to measure GABA activated
      current in dorsal root ganglion neurons that were freshly isolated from adult
      rats, we have confirmed the finding of Tehrani et al. (Synapse, 4 (1989) 126-131)
      using 100 microM GABA; however, the effects of forskolin that were not mimicked
      by 1,9-dideoxyforskolin were not blocked by the kinase inhibitor H-7 (50 microM).
      In contrast, at lower concentrations of GABA (10-20 microM), both forskolin and
      1,9-dideoxyforskolin increased the decay rate of GABA activated current. In
      addition, all effects of forskolin occurred within 200 ms of application of
      forskolin and the effects were not blocked or occluded by H-7, 10 microM cAMP, or
      the active subunit of protein kinase A. We conclude that: (1) 1,9
      dideoxyforskolin is not a reliable indicator of forskolin specificity in this
      system because its effects are dependent upon GABA concentration; and (2) the
      most prominent effects of forskolin on amplitude and decay time course of GABA
      activated ion current are not mediated by cAMP or protein kinase A (PKA).

PMID- 1380878
TI  - Trigeminal nerve endings of lingual mucosa and musculature of the rat.
AB  - Horseradish peroxidase conjugated with wheat germ agglutinin (HRP-WGA) was
      injected into the trigeminal ganglion of adult rats to label the peripheral
      sensory receptors of the tongue. The conjugate was transported anterogradely to
      all the ipsilateral fungiform papillae and filiform papillae. Some labeled fibers
      crossed over to the contralateral papillae. In the intrinsic tongue muscle
      undulating nerve fibers along or across muscle fibers were often observed, and
      formed simple spiral endings.

PMID- 1380879
TI  - Laminin immunohistochemistry in brain is dependent on method of tissue fixation.
AB  - Normal adult and lesioned rat and mouse brains were fixed by formaldehyde
      perfusion by two methods that differ primarily in the length of the post-fixation
      period. Sections were subsequently immunostained using monoclonal and polyclonal
      antibodies to laminin. With relatively short post-fixation periods (up to 4 h),
      vascular basement membrane (BM)-laminin was immunostained, but intraneuronal
      laminin-like immunoreactivity was faint. With longer post-fixation periods (18-24
      h), intraneuronal laminin-like immunoreactivity was distinct, while vascular BM
      laminin immunoreactivity was reduced drastically. These findings are particularly
      relevant to studies examining laminin immunoreactive blood vessels in response to
      lesions, especially ischemic stroke. In fact, the present results suggest that
      the apparent neovascularization or up-regulation of vascular BM-laminin following
      CNS injury likely relates to differences in regional tissue fixation.

PMID- 1380880
TI  - Identification of nociceptive neurons in the medial thalamus: morphological
      studies of nociceptive neurons with intracellular injection of horseradish
      peroxidase.
AB  - Somatosensory neurons including nociceptive ones in the medial thalamus have been
      studied extracellularly, and are classified into three types: nociceptive
      specific, wide dynamic range, and tap neurons. However, the morphological
      characteristics of these three neurons have not yet been clarified. We studied
      the morphological characteristics of the neurons by iontophoretic injection of
      HRP into single neurons in 32 cats. Nine wide dynamic range neurons and two tap
      neurons were electrophysiologically identified and successfully stained with HRP
      in and around the parafascicular and subparafascicular nuclei, and in the
      mediodorsal nucleus. All nine wide dynamic range neurons had fewer dendrites
      which formed scanter tufts, whereas the two tap neurons had many more dendrites
      which formed denser tufts: i.e. wide dynamic range neurons were of the
      isodendritic type, and the tap neurons were of the allodendritic type, according
      to Ramon-Moliner's classification. The axons of the two tap neurons ran antero
      laterally whereas those of wide dynamic range neurons ran in many directions.
      These morphological differences suggest that tap neurons may have more
      specialized and fixed functions than wide dynamic range neurons.

PMID- 1380881
TI  - Glutamine synthetase immunoreactivity in two types of mouse brain glial cells.
AB  - The localization and distribution of glutamine synthetase (GS) in the adult mouse
      brain were studied by immunohistochemistry. GS immunoreactivity was found in two
      morphologically distinct types of glial cells apart from Bergmann glia, one
      asteroid and the other ovoid. The light and electron microscopic features of the
      GS-positive asteroid and ovoid cells were well consistent with those of
      astrocytes and oligodendrocytes, respectively. The GS-positive asteroid cells
      were present in the hippocampus, cerebral cortex, neostriatum, and cerebellar
      granular layer, where many synapse receptors for excitatory amino acids such as
      glutamate are densely distributed. Weakly GS-positive asteroid cells were also
      scattered in the white matter. The GS-positive ovoid cells were present
      throughout the gray matter regions of the brain except for the hippocampus, and
      they were the predominant type of GS-positive cells in the thalamus and brainstem
      gray matter where excitatory amino acid receptors are relatively sparse. No GS
      positive ovoid cells were found in the white matter. These results suggest that,
      in the mouse brain, GS is localized in oligodendrocytes of the gray matter and in
      astrocytes. These two types of GS-positive glial cells may play different roles
      in the metabolism of glutamate.

PMID- 1380882
TI  - Melittin enhances excitatory amino acid release and AMPA-stimulated 45Ca2+ influx
      in cultured neurons.
AB  - Melittin, a potent activator of phospholipase A2, enhanced both spontaneous and
      depolarization-induced release of D-[3H]aspartate in primary cultures of
      cerebellar granule cells. The action of melittin was concentration-dependent
      (EC50 value = 300 ng/ml) and did not require the presence of extracellular Ca2+.
      Melittin also stimulated the release of glutamate and aspartate, in addition to
      other endogenous amino acids (taurine, alanine and gamma-aminobutyric acid).
      These effects were accompanied by an enhanced influx of 45Ca2+, which was in part
      mediated by the activation of excitatory amino acid receptors by endogenous
      agonists. Low concentrations of melittin (50 ng/ml) potentiated the efficacy of
      AMPA in stimulating 45Ca2+ influx without affecting stimulation by kainate or by
      glutamate added in the absence of extracellular Mg2+ (a condition that favors the
      activation of NMDA receptors). These results indicate that activation of
      phospholipase A2 evokes both an enhanced glutamate release and an increased
      sensitivity of AMPA receptors, two events that may support synaptic facilitation
      and LTP formation.

PMID- 1380883
TI  - Xanthine derivatives IBMX and S-9977-2 potentiate transmission at an Aplysia
      central cholinergic synapse.
AB  - In an attempt to investigate the role of cAMP-dependent phosphorylations on
      synaptic transmission at an Aplysia cholinergic buccal ganglion synapse, the
      effects of xanthine derivatives such as 3-isobutyl-1-methylxanthine (IBMX), which
      is well known to inhibit phosphodiesterase activity thereby promoting cAMP
      accumulation, and a novel xanthine derivative, S-9977-2 were evaluated. They were
      found to potentiate cholinergic transmission by significantly increasing the time
      constant of decay (Tc) of inhibitory postsynaptic currents (IPSCs). The
      postsynaptic origin of the phenomenon was supported by the observation that
      responses to the ionophoretic application of acetylcholine (ACh) were also
      potentiated in duration as well as in amplitude. No effects of S-9977-2 on the
      ACh-gated Cl- channel conductance or mean open time were observed. The finding
      that responses to the hydrolysis-resistant cholinergic analogue carbachol were
      unaffected by the two xanthines suggested that the observed effects were at least
      partly caused by an inhibition of acetylcholinesterase (AChE) activity. That
      these substances inhibit AChE activity was confirmed in vitro. Phosphorylation
      processes nonetheless appear to be partly involved in the synaptic effect of the
      xanthines as the kinase blocker H-8 blocked part of the IPSC Tc lengthening.
      Possible mechanisms are discussed.

PMID- 1380884
TI  - Pain control. Barriers to the use of available information. World Health
      Organization Expert Committee on Cancer Pain Relief and Active Supportive Care.
AB  - One of the World Health Organization's (WHO) top priorities is cancer pain
      relief. Simple guidelines for assessing and relieving pain have been developed,
      published, and field tested. WHO has concluded that there is enough knowledge
      currently to permit an approach to cancer pain relief that can be implemented on
      a worldwide basis. This information, when used correctly, allows pain control in
      75% or more of patients with cancer pain. However, numerous barriers prevent the
      application of this knowledge and the achievement of cancer pain relief.
      Assessing the patient's cancer pain and effective use of analgesic drugs,
      especially opioid agents, are hampered by a lack of education of health-care
      professionals and the fact that the pain sensation is entirely subjective.
      Unfortunately, these factors often result in pain management being determined on
      the basis of personal opinion rather than scientific knowledge. This leads to
      inconsistent and often inadequate care of patients with cancer pain. The extent
      of the cancer pain problem and the WHO analgesic-ladder approach to cancer pain
      relief are reviewed along with recommendations from the American Pain Society.
      Lack of education of health-care professionals is discussed, focusing on pain
      assessment, underuse of oral and rectal routes of administration, fears of
      addiction, and titration of doses of opioid drugs. Simple strategies for
      beginning to correct these problems are presented.

PMID- 1380885
TI  - Specific diagnosis by CT and HRCT in six chronic lung diseases.
AB  - CT and high-resolution CT (HRCT) are both important modalities for imaging lung
      chronic disease, and certain features (distribution of disease in the axial
      plane, unilateral or bilateral disease, bronchovascular bundle thickening, septal
      thickening, central dot thickening, polygons, distortion of parenchyma, air-space
      disease, nodules) are well known to suggest specific diagnoses. In a series of 54
      consecutive patients with six specific diseases (scleroderma or UIP, sarcoidosis,
      lymphangitic carcinomatosis, drug toxicity, lymphomas, eosinophilic granuloma),
      these diagnostic CT features were always present. In 50/54 cases, a histologic
      proof was obtained. In 36 patients with histologic confirmation of four different
      diseases and in six normal controls, we compared sensibility, specificity, and
      accuracy of chest radiography, chest CT, and HRCT and found the highest
      diagnostic accuracy by HRCT together with standard CT.

PMID- 1380886
TI  - Expression of human prostatic acid phosphatase activity and the growth of
      prostate carcinoma cells.
AB  - Human prostatic acid phosphatase (PAcP) is a tissue-specific differentiation
      antigen and is the major phosphotyrosyl (p-tyr) protein phosphatase in normal
      differentiated prostate epithelial cells. In prostate carcinomas, cellular PAcP
      has a low expression. We examined the expression of cellular PAcP activity and
      its correlation with cell growth that may lead us to understand the role of
      tyrosine phosphorylation in human prostate cells. LNCaP cells, which expressed
      the highest cellular PAcP activity, had the slowest growth rate and the lowest p
      tyr level among three human prostate carcinoma cell lines: LNCaP, DU145, and PC
      3. This inverse correlation was further examined in LNCaP cells, since these
      cells remain hormone-sensitive. Androgen, a classical stimulator of prostate
      cells, stimulated the growth of LNCaP cells while cellular PAcP activity
      decreased and p-tyr levels increased. This phenomenon was also observed when
      cells were treated with epidermal growth factor and fetal bovine serum. Both
      epidermal growth factor and fetal bovine serum stimulated the growth of LNCaP
      cells whereas cellular PAcP activity decreased. Furthermore, when cell growth was
      arrested at low temperatures (23 degrees C), cellular PAcP activity was elevated.
      To establish the relationship of cellular PAcP activity with cell growth rate, we
      transfected a complementary DNA encoding the full length PAcP protein into
      another human prostate carcinoma line, PC-3, that lacks endogenous PAcP. Two
      stable transfectants, designated PC-18 and PC-416 cells, were obtained and shown
      to express PAcP mRNA transcribed from the transfected complementary DNA. The
      expression of PAcP activity in PC-416 cells, but not PC-18 cells, was associated
      with a lower p-tyr level and a slower growth rate than control cells transfected
      with the expression vector alone. In conclusion, in LNCaP cells, the stimulated
      cell growth is associated with an increased p-tyr level and a decreased cellular
      PAcP activity. In PAcP complementary DNA-transfected PC-416 cells, the low level
      of p-tyr corresponds to a slow growth rate.

PMID- 1380887
TI  - Down-regulation of tenascin expression by antiprogestins during terminal
      differentiation of rat mammary tumors.
AB  - Studies on tenascin expression in hormonally dependent growing tissues of breast
      and endometrium suggested that its expression parallels the progression of normal
      or malignant proliferative alteration of the tissue. With the study presented
      here we addressed the question of whether antiprogestin-induced terminal
      differentiation down-regulates tenascin expression. By comparative
      immunolocalization of tenascin in sections of untreated 7,12
      dimethylbenz[alpha]anthracene-induced tumors, tumors grown in ovariectomized
      animals, tamoxifen-treated tumors, and antiprogestin-treated tumors, we obtained
      the following results. (a) The entire extracellular space of the stromal
      mesenchyme was filled by tenascin immunoreactivity in cases of untreated control
      tumors. (b) Both ovariectomy and antiestrogen treatment with tamoxifen did not
      affect the overall staining pattern and resulted in a slight increase of the
      arbitrarily judged staining intensity. (c) Within antiprogestin-treated tumors
      tenascin-like immunoreactivity predominantly was restricted to fiber-like,
      collagenous connective tissue structures, which appeared in the stromal
      compartment as a result of the antiprogestin treatment. In large areas of the
      tumor composed of apparently secretory active tumor cells we failed to
      immunolocalize tenascin. Our results provide further evidence that expression of
      tenascin reflects both benign and malignant proliferative alterations of the
      tissue, whereas its down-regulation is correlated to differentiation of the
      tissue. Additionally, evidence is provided that the mechanism of tumor growth
      inhibition by antiprogestins indeed is induction of terminal differentiation of
      tumor cells.

PMID- 1380888
TI  - Sensitive detection of rare circulating neuroblastoma cells by the reverse
      transcriptase-polymerase chain reaction.
AB  - The presence of circulating tumor cells in patients with localized or
      disseminated neuroblastoma may be a significant prognostic factor at diagnosis
      and may antedate the detection of relapse by other diagnostic studies. We report
      the development of a highly sensitive detection assay for circulating neuroblasts
      based on the reverse transcriptase-polymerase chain reaction (RT-PCR), using the
      neuroendocrine protein gene product 9.5 (PGP 9.5) as the tumor marker. Analysis
      of RT-PCR products by agarose gel electrophoresis demonstrated that neuroblastoma
      cell lines were uniformly positive, whereas peripheral blood mononuclear cells
      were negative. Alkaline Southern blotting with a PGP 9.5-specific probe revealed
      scant expression of PGP 9.5 in peripheral blood mononuclear cells, well below the
      limits of detection by electrophoresis alone. The system was able to detect a
      single neuroblastoma cell in 10(7) peripheral blood mononuclear cells. Eighteen
      patient samples were analyzed by PGP 9.5 RT-PCR and the results compared with
      immunocytology in 16. Ten of the 18 were negative by both studies. Eight of the
      18 were positive by PGP 9.5 RT-PCR, 4 of which were also positive by
      immunocytology. PGP 9.5 RT-PCR was able to detect circulating neuroblasts in two
      patients with negative immunocytology, the first with progressive bone marrow
      disease and the second at high risk for relapse but no other evidence of disease.
      PGP 9.5 RT-PCR allows the detection of circulating neuroblastoma cells with a
      sensitivity greater than immunocytology. It will be useful in evaluating the
      clinical significance of circulating tumor cells with respect to prognosis and
      early detection of relapse, and in the screening of peripheral stem cell harvests
      prior to autologous infusion.

PMID- 1380889
TI  - Influence of tamoxifen on plasma levels of insulin-like growth factor I and
      insulin-like growth factor binding protein I in breast cancer patients.
AB  - Plasma levels of insulin-like growth factor I (IGF-I) and insulin-like growth
      factor binding protein I (IGFBP-I) were measured in fasting blood samples
      obtained from 16 postmenopausal breast cancer patients before and during
      tamoxifen treatment for 1 to 6 months. Tamoxifen suppressed total plasma IGF-I by
      a mean of 28.5% (P less than 0.001) but elevated plasma IGFBP-I by a mean value
      of 78% (P less than 0.001). Changes in plasma levels of growth hormone, insulin,
      or insulin C-peptide were not observed. These findings suggest that tamoxifen
      exerts its influence on plasma IGF-I and IGFBP-I by mechanisms other than those
      known to regulate the plasma levels of these peptides, primarily growth hormone
      and insulin, respectively. A dual effect suppressing plasma IGF-I and elevating
      plasma IGFBP-I suggests that tamoxifen may have a significant influence on
      endocrine and possibly paracrine delivery of IGF-I to breast cancer cells in
      vivo.

PMID- 1380891
TI  - Characterization of protein tyrosine kinases from human breast cancer:
      involvement of the c-src oncogene product.
AB  - Tyrosine phosphorylation is an important regulatory mechanism in response to the
      action of growth factors and oncogenes. Since many oncogenes code for tyrosine
      kinases, increased or altered oncogene expression may be reflected in increased
      tyrosine kinase activity. In a recent study (Hennipman et al., Cancer Res., 49:
      516-521, 1989), we found that the tyrosine kinase activity of the cytosolic and
      membrane fractions of malignant human breast tissue was significantly higher
      compared to the benign or the normal breast tissue. Moreover, the increase in the
      cytosolic fractions was found to be of prognostic value. In the present study we
      determined the protein tyrosine kinase (PTK) activity of another 72 breast cancer
      specimens, and it could be shown again that the PTK activity in all 72 of these
      tumors was elevated compared to normal controls. We characterized these cytosolic
      PTKs by anion exchange chromatography using fast protein liquid chromatography,
      and it could be shown that at least two different forms of PTK exist. Using
      antibodies against a number of known oncogene products, we could determine that
      at least 70% of the PTK activity in the cytosol originated from the presence of
      the c-src oncogene product. Both of the PTK activity peaks seen in the fast
      protein liquid chromatography patterns could be precipitated with the anti-Src
      antibody. Furthermore, using the MCF-7 breast cancer cell line, it could be shown
      that the antibody against c-src also precipitated a part of the cytosolic PTK
      activity. In normal human peripheral lymphocytes, no precipitation of the
      cytosolic and membrane PTK activity could be achieved using the anti-Src
      antibody. Inasmuch as the cytosolic PTK activity parallels the malignancy in
      breast tumors (Hennipman et al., Cancer Res., 49: 516-521, 1989), and the
      majority of this activity is precipitated by anti-Src antibodies, the c-src
      protooncogene may play a key role in the manifestation of breast cancer.

PMID- 1380890
TI  - Resistance of human cervical carcinoma cells to tumor necrosis factor correlates
      with their increased sensitivity to cisplatin: evidence of a role for DNA repair
      and epidermal growth factor receptor.
AB  - Alterations in cellular biochemistry which are associated with the development of
      resistance to cytotoxic peptides, such as tumor necrosis factor (TNF), may also
      be responsible for changes in the response of cells to cytotoxic agents.
      Culturing ME-180 cervical carcinoma cells in the presence of escalating
      concentrations of TNF resulted in the development of an ME-180 cell variant (ME
      180R) resistant to TNF but expressing a 3-5-fold increased sensitivity to
      cisplatin (CDDP) when measured following continuous exposure (low doses) or short
      term incubation with CDDP (high doses) and clonogenic analysis. Cellular platinum
      uptake, efflux, and nuclear platinum content as well as the extent of DNA
      platination were examined and found to be identical in both ME-180 parental and
      ME-180R cell lines. Although ME-180R cells showed a relatively higher glutathione
      content than ME-180 parental cells, the effect of buthionine sulfoximine on the
      cellular sensitivity to CDDP and glutathione S-transferase activities of both
      cell lines were almost identical, suggesting that glutathione content or its
      metabolism did not appear to play a major role in differential CDDP cytotoxicity.
      Unscheduled DNA synthesis following exposure to CDDP was more inducible in ME-180
      parental cells than in CDDP-sensitive ME-180R cells. Alkaline elution studies of
      cross-linked DNA in CDDP-treated ME-180 cells suggested that accumulation of DNA
      adducts reached maximal levels 10-15 h after CDDP treatment and was similar in
      both TNF-resistant and parental cells. Within 24 h after CDDP exposure, the
      extent of DNA cross-linking was markedly reduced in parental cells but remained
      elevated in the CDDP-sensitive ME-180R cell line. To examine the proposed
      regulatory role of phosphorylation in CDDP and TNF-mediated cytotoxicity,
      epidermal growth factor (EGF) receptor tyrosine kinase activity was measured in
      both TNF-resistant and parental ME-180 cells. Analysis of cell lysates
      demonstrated a 3-4-fold higher EGF receptor tyrosine kinase activity in ME-180R
      cells when compared to the parental population which correlated with increased
      expression of EGF receptor protein by immunoblot analysis. Based upon colony
      forming assays, EGF treatment of ME-180 parental cells resulted in an increased
      sensitivity to CDDP (similar to ME-180R cells) and 3-fold stimulation of EGF
      receptor tyrosine kinase activity. Taken together, these results suggest that TNF
      resistance in ME-180 cervical carcinoma cells correlates with both increased EGF
      receptor expression and enhanced CDDP cytotoxicity.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1380892
TI  - Stereocontrolled synthesis of sialyl Lewis X ceramide consisting of a
      pentasaccharide recognized by the selectin family.

PMID- 1380893
TI  - Detection of allogeneic Qa/TL and Ly specificities on murine tumor cells with IgD
      in tumor-regressor serum.
AB  - Serum from C3H/He mice, which show regression of MM2 tumor cells after
      transplantation and removal (regressor serum, RS) contains non-gammaglobulin
      components that cross-react with various tumor cells of mice [22, 23]. In
      addition to tumor cells, various allogeneic lymphocytes are also susceptible to
      an RS-dependent lymphocyte-mediated cytotoxic reaction. To identify tumor cell
      surface antigens that cause the cross-reactive host response, the serum
      components were analyzed by absorption of RS with allogeneic lymphocytes. RS
      components were found to recognize allogeneic lymphocyte antigens including Qa-2
      and Ly6.2. Specificity for the Qa-2 antigen was further tested using Qa-2
      congenic mice. The expression of Qa-2 antigen was detected on the surfaces of MM2
      and other tumor cells derived from H-2k mice (seven among nine cell lines tested)
      by a membrane immunofluorescence method using a Qa-2-specific mAb. Physical
      characteristics of the Qa-2-specific component in RS were determined and found to
      differ from those of regular IgGs but to be similar to those of IgDs. Using an
      enzyme-linked immunosorbent assay with an IgD-specific mAb and Qa-2-lacZ fusion
      protein, the existence of IgD in RS with specificity for Qa-2 was confirmed.
      These results suggest that the RS component with Qa-2 specificity is an IgD, the
      specificity and physiological role of which are unknown.

PMID- 1380894
TI  - Silencing of immunodominant epitopes by contiguous sequences in complex synthetic
      peptides.
AB  - We have previously shown that the T cell response to the synthetic peptide cI12
      26:NP365-380 (covalently linked epitopes of lambda repressor (cI) and influenza A
      nucleoprotein (NP) polypeptides) requires amino acid sequences located in the
      junctional region between the cI12-26 and NP365-380 epitopes in the H-2d and H-2k
      haplotypes. In this study, we show that the dominant epitope of cI12-26:NP365-380
      in H-2b mice is also located within the junctional region of the peptide,
      indicating that the same amino acid sequence is immunodominant in three different
      H-2 haplotypes. Based on results using fixed APC, there was no qualitative
      difference in epitope recognition due to antigen processing. In addition, antigen
      presentation by APC expressing mutant I-A molecules constructed by hemiexon
      shuffling of regions of the molecule containing primarily beta sheet or alpha
      helix showed that many different substitutions were permissive for at least one
      of the T hybridomas. More importantly, however, when the junctional sequences are
      covalently linked in composite synthetic peptides containing additional
      previously defined T cell epitopes, antigenicity of the immunodominant junctional
      region was silenced and a new epitope assumed immunodominance. Thus,
      immunodominance does not correlate with the primary amino acid sequence of the
      potential epitope. Instead, the immunodominant epitope is determined by complex
      interactions among the epitopes, which most likely depend on the structural
      conformation of the composite peptide.

PMID- 1380895
TI  - Induction of strong homotypic adhesion in human T cell lines positive with human
      T-cell leukemia virus type 1 by monoclonal antibodies to MHC class I and beta 2
      microglobulin.
AB  - To identify the cellular receptors and other cell surface molecules playing
      essential roles in the transmission of human T-cell leukemia virus type 1 (HTLV
      1), we have been isolating monoclonal antibodies (mAbs) that are capable of
      inhibiting HTLV-1-induced syncytium formation. In the present study, we isolated
      two mAbs, H11 (IgM) and H14 (IgG1), inhibitory to syncytium formation in the
      coculture of TOM-1 or C91/PL (both HTLV-1-positive human T-cell lines) and MOLT
      4/8 (HTLV-1-negative human T-cell line) by immunizing the membrane fraction of
      human osteosarcoma line HOS. By immunoprecipitation and immunoblotting, H11 and
      H14 were found to be specific for MHC class I heavy chain and beta 2
      microglobulin (beta 2 M), respectively. Among the four commercially obtained
      mAbs, two mAbs for MHC class I antigen and two mAbs to beta 2 M, one mAb to MHC
      class I antigen and one mAb to beta 2 M were also found to be inhibitory to the
      syncytium formation. The functional comparison of these mAbs revealed that the
      syncytium-inhibitory mAbs induced strong homotypic cell adhesion particularly in
      the HTLV-1-positive T-cell lines. This cell adhesion was dependent on
      temperature, energy metabolism, and microfilament function but not on the
      activity of protein kinase C or divalent cations. These results suggest a novel
      type of LFA-1-independent cell adhesion induced by signal transduction via MHC
      class I antigen.

PMID- 1380896
TI  - Modulation of human lymphocyte marker expression by gamma irradiation and
      mitomycin C.
AB  - gamma irradiation (GR) or mitomycin C (MC) treatment of stimulator cells is
      frequently used to achieve unidirectionality of response in the mixed lymphocyte
      reaction. As GR differs from MC in the pathways used to block lymphocyte
      replication, this study analyzes the effects of these modalities upon the
      expression of various differentiation and Class II major histocompatibility
      antigens on lymphocytes cultured for 24, 48, and 72 hr. There was a decrease in
      the mean density of HLA-DR expression on CD3+ and on CD8+ cells at 24, 48, and 72
      hr after exposure to GR (42 and 35, 60 and 69, and 26 and 49%, respectively) or
      to MC (26 and 11, 26 and 18, and 46 and 30%, respectively). There was a parallel
      decrease in the levels of the corresponding cell subsets when compared with
      control cultured cells not exposed to GR or MC. In contrast, the density of HLA
      DR markers on CD3-negative cells was increased at 24, 48, and 72 hr of culture
      following exposure to GR (73, 82, and 102%, respectively) or to MC (9, 45, and
      80%, respectively). There was a more profound decrease in CD3+, CD8+, and CD19+
      cell subset levels and in the density of the corresponding markers in GR-treated
      cells than in those of cells exposed to MC when the results were compared with
      those of untreated cultured control cells. Although GR appears to exert a more
      profound effect than MC, the results indicate that both modalities have the
      capacity to reduce the density of polymorphic determinants on Class II (HLA-D
      region)-encoded molecules on T (CD3+ and CD8+) and B (CD19+) cells which are
      known to trigger potent MLR responses. Both modalities may therefore affect
      profoundly the relative strength of MLC responses and the derived measurements of
      the degree of HLA Class II compatibility between stimulator and responder cells.

PMID- 1380897
TI  - Antibodies to adhesion molecules inhibit the lytic function of MHC-unrestricted
      cytotoxic cells by preventing their activation.
AB  - We evaluated the effect of the antibodies to adhesion molecules CD2, CD11a/CD18
      (LFA-1), and CD56 (N-CAM) on MHC-unrestricted cytotoxicity mediated by polyclonal
      NK cells and LAK cells or by CD3+ or CD3- cytolytic cell clones against a panel
      of tumor cell targets selected according to expression or absence of the
      corresponding ligands. We show that (i) antibodies to CD11a/CD18 and, to a lesser
      extent, antibodies to CD2 inhibit target cell lysis, whereas anti-CD56 antibodies
      exert little if any effect; (ii) in a model system using polyclonal NK/LAK cells
      as effectors and K562 or HL60-R (NK-resistant) cells as targets, inhibition of
      cytotoxicity occurs without a significant impairment of effector to target cell
      binding; (iii) the cytotoxic function of CD3+ or CD3- cytotoxic cell clones is
      inhibited differentially by antibodies to adhesion molecules; (iv) conjugates
      formed in the presence of antibodies which inhibit target cell lysis display a
      significant reduction of target to effector cell contact surface; and (v) this
      may lead to defective activation of effector cells, as indicated by lack of
      redistribution of the microtubular apparatus. We conclude that (i) MHC
      unrestricted cytotoxicity is regulated by a number of molecular interactions that
      span far beyond our present knowledge and that it is strictly dependent on the
      surface phenotype of the effector cell and of the target cell; (ii) in certain
      types of effector/target cell interactions, antibodies to adhesion molecules do
      not prevent conjugate formation but reduce the extent of cell-to-cell surface
      contact which, in turn, leads to defective activation of the effector cell and,
      therefore, to inhibition of target cell lysis.

PMID- 1380899
TI  - Developmental changes in the effects of drugs acting at NMDA or non-NMDA
      receptors on synaptic transmission in the chick cochlear nucleus (nuc.
      magnocellularis).
AB  - The developmental pharmacology of excitatory amino acid (EAA) receptors in the
      chick cochlear nucleus (nucleus magnocellularis, NM) was studied by means of bath
      application of drugs and recording of synaptically-evoked field potentials in
      brain slices taken from chicks aged embryonic day (E) 14 through hatching (E21).
      The abilities of various EAA agonists (N-methyl-D-aspartate [NMDA], kainic acid,
      and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]) to suppress
      postsynaptic responses by depolarization block and of EAA antagonists ((3-[RS]-2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid [CCP], dizocilpine [MK-801], 6
      nitro-7-sulfamoyl-benzo(F)quinoxaline-2,3 dione [NBQX], 6-cyano-7
      nitroquinoxaline-2,3-dione [CNQX] and 6,7-dinitroquinoxaline-2,3-dione [DNQX]) to
      suppress these responses directly were assessed quantitatively. The results
      support the existence of NMDA receptors in NM and suggest that the ability of
      these receptors to influence synaptically-evoked responses declines dramatically
      during the last week of embryonic life. The results similarly suggest that the
      non-NMDA receptors in NM undergo changes in density and/or function during a
      period of development when the cochlear nucleus is undergoing a variety of
      morphological and functional transformations.

PMID- 1380900
TI  - Galanin-like immunoreactivity in the adult and developing Brazilian opossum
      brain.
AB  - The distribution of galanin-like immunoreactivity has been characterized in the
      brain of the adult and developing Brazilian opossum (Monodelphis domestica). Two
      commercially available antisera were used to examine the distribution of galanin
      like immunoreactive (GAL-IR) cells and fibers. Nuclear groups containing GAL-IR
      cell bodies and fibers were seen throughout the adult opossum brain. The
      distribution of GAL-IR elements seen is similar to that reported for other
      mammals. Based on these findings, we believe that galanin may have similar
      physiological functions in the adult Brazilian opossum as has been reported for
      other mammals. In the developing brain, GAL-IR structures were seen as early as 1
      day postnatal (PN) in the developing hypothalamus and brainstem. By days 5 and 10
      PN, there was a robust expression of galanin-like immunoreactivity in specific
      regions of the brain. Since neurogenesis and brain morphogenesis are actively
      occuring postnatally in the opossum, galanin may be playing a role in the
      differentation of specific regions of the brain.

PMID- 1380898
TI  - Hyaluronan and cell locomotion.
AB  - Hyaluronan (HA), a glycosaminoglycan, has long been implicated in cell
      locomotion. We have shown that HA production regulates the locomotion of H-ras
      transformed cells. This autocrine motility mechanism is mediated by a novel HA
      receptor termed RHAMM, an acronym for Receptor for HA Mediated Motility. HA:RHAMM
      interactions regulate directional locomotion of tumor cells and result in
      enhanced protein tyrosine phosphorylation that may be a critical messenger
      mechanism for initiation of locomotion.

PMID- 1380901
TI  - Early myelination in zitter rat: morphological, immunocytochemical and
      morphometric studies.
AB  - Early myelination in zitter rat was investigated by light and electron
      microscopic observations, by immunostaining for myelin basic protein (MBP),
      proteolipid protein (PLP) and myelin-associated glycoprotein (MAG), and by
      morphometric analysis from the 1st to the 28th day of age. Although the
      commencement of myelination in zitter rats was not delayed in comparison with
      control rats, the density or the number of myelinated fibers in zitter rats was
      significantly below that in controls, both in the ventral column of the cervical
      spinal cord and in the optic nerve. In contrast, the density or the number of
      aberrant myelin sheaths was increased in zitter rats, and this difference became
      more marked with increasing age. The persistent presence of abnormal membranous
      structures associated with the oligodendroglial nuclear membrane and the
      increased number of aberrant myelin sheaths were characteristic to the zitter
      mutation, although these alterations were also observed transiently in control
      rats. Quantitative analysis supported the proposition that hypomyelination in
      zitter rats is primarily pathological and becomes more prominent with advancing
      age. However, the fundamental structure of the myelin lamellae appeared to be
      normal and the immunoreactivities for MBP, PLP and MAG were slightly delayed and
      weakend in comparison with age-matched controls. Thus, in zitter rat there is the
      functional abnormality of the oligodendrocytes to integrate the processes of
      membrane biosynthesis and to expel excessive production of membranous structures
      associated with the membranous organellae such as nuclear membrane, and it is
      postulated that this functional abnormality is characteristic to only the zitter
      mutation.

PMID- 1380902
TI  - Adrenergic expression in the rat adrenal gland: multiple developmental regulatory
      mechanisms.
AB  - Phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) has been used as a
      marker to examine development of adrenergic expression in the rat adrenal gland
      and the putative role of glucocorticoids in this process. PNMT enzymatic activity
      increases 7-10-fold from birth to postnatal day 35. Immunotitration studies show
      that PNMT protein only increases 4-5-fold during this same time period. Moreover,
      the slopes from the immunotitration curves decrease with increasing age. Thus, a
      more active enzyme with lower affinity for the antiserum appears to be present in
      the older animals. Quantitative solution hybridization shows that PNMT mRNA
      increases 2.5-fold from birth through postnatal day 11. Thereafter, it declines,
      and eventually plateaus at values insignificantly different from birth by
      postnatal day 25. Northern analysis further shows that two forms of PNMT mRNA are
      expressed. Adrenal corticosterone remains low from birth through postnatal day
      11, but then increases nearly 10-fold by adulthood. The lack of concordance
      between changes in PNMT activity, protein, and mRNA suggests that adrenergic
      expression is developmentally regulated at multiple levels; the above provides
      evidence for both transcriptional and post-transcriptional controls, since
      changes in PNMT mRNA may differ in both magnitude and direction from changes in
      PNMT activity and protein during the developmental window examined. These
      developmental regulatory mechanisms may be in part glucocortocoid-mediated, but
      corticosteroid control of PNMT gene expression does not appear to be the
      predominant mechanism of control.

PMID- 1380903
TI  - Induction of molecular layer ectopias by puncture wounds in newborn rats and
      mice.
AB  - Molecular layer ectopias spontaneously occur in immune-disordered mice, and the
      accompanying paper demonstrates that these ectopias are associated with a break
      in the external glial limiting membrane and with distortion of radial glial
      fibers at birth. It was hypothesized that injury to the developing neocortex is
      the main etiologic event for molecular layer ectopias. To test this hypothesis,
      puncture wounds were made on the surface of the cerebral cortex of newborn rats
      and mice. These wounds produced, in adulthood, molecular layer ectopias similar
      in appearance to those seen spontaneously in immune-disordered mice. Further,
      these ectopias show similar distortions of radial glial fibers during
      development, and of neurofilaments in adulthood. This work supports the notion
      that injury could be a factor in the production of molecular layer ectopias.

PMID- 1380905
TI  - Diffusion of tosufloxacin into prostatic tissue.
AB  - The diffusion of tosufloxacin (TFLX) into the prostatic tissue was studied in 25
      patients with benign prostatic hypertrophy. TFLX concentrations in the serum and
      prostatic tissue were measured at scheduled intervals after oral administration
      of 450 mg of TFLX on the day before surgery, followed by administration of 150 mg
      of TFLX immediately before surgery. The mean TFLX levels in prostatic tissue (and
      tissue/serum levels) at 2, 4 and 6 h were 0.35 +/- 0.16 microgram/g (0.93 +/-
      0.36) in 7 patients, 0.58 +/- 0.92 microgram/g (1.10 +/- 0.45) in 10 patients and
      0.22 +/- 0.09 microgram/g (0.95 +/- 0.45) in 8 patients. The TFLX levels in
      prostatic tissue exceeded the minimum inhibitory concentration for several
      pathogenic bacteria detected in the infected prostatic fluid. Therefore, TFLX
      shows promise as a useful drug in the treatment of bacterial prostatitis and
      infections developing after prostatic surgery.

PMID- 1380906
TI  - Development of effective drug combinations for the inhibition of multiply
      resistant mycobacteria, especially of the Mycobacterium avium complex.
AB  - Rationally designed combinations of rifampicin (RAMP) and thiacetazone plus
      isonicotinic acid hydrazide and/or ethambutol are highly effective in the
      treatment of patients (including HIV-positive) infected with multiply resistant
      mycobacteria of the Mycobacterium avium complex (MAC). Clinical results are very
      promising. The high efficacy of these combinations is due to the synergistic
      potentiation of single-drug activities. As soon as rifabutin is marketed, it
      should replace RAMP in the combination treatment of patients with highly RAMP
      resistant MAC bacteria.

PMID- 1380904
TI  - Effect of long-term use of Norplant implants on haemostatic function.
AB  - This study describes the effects of Norplant on haemostatic function after 5
      years of use in 97 women. There was a decrease in vitamin-K dependent Factors II,
      V, VII and reduction in fibrinolytic activity at 2 and 4 years of use. Increased
      platelet numbers and accelerated platelet aggregation were found throughout the 5
      years of Norplant use, whilst raised alpha 2-Macroglobulin (a2-M) and
      antithrombin III (ATIII) antigen level were observed for up to 4 years of use.
      Prolonged Norplant use does not appear to activate the coagulation system and
      does not enhance a state of hypercoagulation.

PMID- 1380907
TI  - [Repertoire of epitopes of human immunodeficiency virus proteins and the search
      for vaccines and diagnostic kits].

PMID- 1380908
TI  - American Association of Electrodiagnostic Medicine, 38th annual meeting.
      Vancouver, 25-28 September 1991. Abstracts.

PMID- 1380909
TI  - Changes in motor and sensory nerve conduction parameters with temperature in
      normal and diseased nerve.
AB  - The effects of temperature on conventional motor and sensory nerve conduction
      parameters were studied in normals and in some pathological conditions. Surface
      stimulating and recording electrodes were used to examine the function of the
      median nerve. The motor and sensory conduction velocities, the parameters of
      compound muscle action and sensory nerve potentials were correlated with skin
      temperature. In the control subjects all nerve conduction parameters changed with
      temperature. These findings were similar to those published previously, but the
      mean slope for MCV was lower than that reported in the literature. The amplitude
      values widely scattered as a consequence of methodological factors, which may
      mask effects of temperature. Only minor differences were revealed between control
      subjects and patients. The effect of temperature proved to be similar in the
      patients and in the normal controls. Therefore, the correction factors determined
      in normals may be acceptable for abnormal nerves in standardising the measured
      values with respect to temperature. However, in pathological cases, above all in
      diabetes mellitus, the slightly reduced changes of conduction velocities vs.
      temperature may be the source of false negative results in borderline cases when
      using the normal correction factors. The combination of preserved temperature
      dependence but decreased conduction velocities may indicate that demyelination
      and temperature influence the conduction velocities via different mechanisms.

PMID- 1380910
TI  - Human startle reflex: technique and criteria for abnormal response.
AB  - Because quantitative norms for the normal audiogenic startle response to repeated
      stimuli have not been previously reported, we now describe a technique for
      eliciting the startle response and analysing its habituation with repeated
      stimuli. We used binaural 105 dB tones delivered in 5 blocks of 4 tones.
      Successive blocks were separated by a 5 min period without tones stimuli and had
      progressively shorter inter-stimulus intervals (ISIs) beginning with 5 min in the
      first block and reducing to 1 min in the final, fifth block. We contrast the
      response and its habituation in a group of 8 normal subjects with that in a
      patient with clinically exaggerated startle. Based on the differences observed,
      we propose that the following criteria may be used to ascertain an abnormally
      increased startle response: (1) excessive duration of the myogenic response; (2)
      persistence of extracranial responses after the initial two blocks of stimuli;
      and (3) reduced habituation of the response (as measured by decreases in response
      duration and in the area under the curve of rectified EMG for the orbicularis
      oculi myogenic response). Our patient was abnormal on each of these measures.
      This result is consistent with past qualitative reports which have indicated that
      abnormal startle is associated both with excessive startle and with subnormal
      habituation. Study of further patients with hyperekplexia will be necessary to
      either confirm our data or modify our proposed criteria.

PMID- 1380911
TI  - Repetitive doublets of human motoneurones: analysis of interspike intervals and
      recruitment pattern.
AB  - In order to study the probable mechanisms of repetitive doublets in human
      motoneurones, the firing patterns of single motor units (MUs) of the trapezius
      were analysed during a weak voluntary muscle contraction. The mean frequencies of
      MUs were 9.4-21.7 imp/sec (the mean interspike interval ranged from 46.0 to 106.7
      msec). Repetitive doublets (up to 28 in succession) were recorded in 21 out of
      120 MUs, mostly at the onset of a slow recruitment. These were followed by single
      discharges. Intradoublet intervals ranged between 2.5 and 20.0 msec. A
      significant difference between single spike firing and doublet firing was
      revealed by plotting interspike interval histograms, showing that two distinct
      mechanisms were involved. The analysis of interspike interval successions
      belonging to several MUs firing simultaneously showed that one of the MUs could
      start with doublets while the others went on firing single spikes with the
      regular mean frequency and interspike interval scatter. The results lead us to
      suggest that the intrinsic properties of motoneurones can be regarded as the main
      factor in the origin of repetitive doublets. It seems that a descending synaptic
      drive also contributes to the control of double firing since in a number of cases
      no doublets were produced at the beginning of MU activity. The findings are
      discussed with regard to the problems of regulating repetitive firing of human
      motoneurones by after-potentials. Steady delayed depolarization is assumed to be
      a possible mechanism of repetitive doublets.

PMID- 1380912
TI  - Motor potentials of inferior orbicularis oculi muscle to transcranial magnetic
      stimulation. Comparison with responses to electrical peripheral stimulation of
      facial nerve.
AB  - Magnetic stimulation at the vertex evoked a motor potential (MP) in the inferior
      orbicularis oculi muscle of 10 healthy subjects with an onset latency of 8-13
      msec. Its amplitude increased and its latency decreased when the muscle was
      contracted: the latency measured 9.5 +/- 1.3 msec with an intensity of
      stimulation 10-15% above threshold in the contracted muscle. This MP is secondary
      to excitation of the motor cortex. With the coil placed over the occipital scalp
      and the same stimulation intensity, an MP was recorded with an onset latency at
      4.5 +/- 0.6 msec. This response reflects the activation of the facial nerve root.
      The peripheral electrical stimulation of the facial nerve at the mandible angle
      elicited an MP with an onset latency at 3.5 +/- 0.4 msec. Most records showed the
      presence of late components at about 30 msec for all types of stimulation.

PMID- 1380913
TI  - Determining the site of stimulation during magnetic stimulation of a peripheral
      nerve.
AB  - Magnetic stimulation has not been routinely used for studies of peripheral nerve
      conduction primarily because of uncertainty about the location of the stimulation
      site. We performed several experiments to locate the site of nerve stimulation.
      Uniform latency shifts, similar to those that can be obtained during electrical
      stimulation, were observed when a magnetic coil was moved along the median nerve
      in the region of the elbow, thereby ensuring that the properties of the nerve and
      surrounding volume conductor were uniform. By evoking muscle responses both
      electrically and magnetically and matching their latencies, amplitudes and
      shapes, the site of stimulation was determined to be 3.0 +/- 0.5 cm from the
      center of an 8-shaped coil toward the coil handle. When the polarity of the
      current was reversed by rotating the coil, the latency of the evoked response
      shifted by 0.65 +/- 0.05 msec, which implies that the site of stimulation was
      displaced 4.1 +/- 0.5 cm. Additional evidence of cathode- and anode-like behavior
      during magnetic stimulation comes from observations of preferential activation of
      motor responses over H-reflexes with stimulation of a distal site, and of
      preferential activation of H-reflexes over motor responses with stimulation of a
      proximal site. Analogous behavior is observed with electrical stimulation. These
      experiments were motivated by, and are qualitatively consistent with, a
      mathematical model of magnetic stimulation of an axon.

PMID- 1380914
TI  - Cerebello-frontal cortical projections in humans studied with the magnetic coil.
AB  - Focal stimulation over human cerebellum with a figure 8 magnetic coil (MC)
      results in an evoked wave recorded from bipolar scalp electrodes on the
      interaural line and more anteriorly. In 3 subjects, the wave responses along the
      interaural line had latencies of 8.8-13.8 msec, lasted 17.4-29.0 msec and had a
      maximum amplitude of 14.4-26.8 microV. The responses were recorded more
      anteriorly from leads midway between the interaural line and frontal leads;
      responses recorded from frontal leads were up to 3.5 msec later. The evoked wave
      was preceded by a diphasic EMG response with a latency of 1.2-2.0 msec. Analysis
      of the averaged responses recorded by adjoining bipolar leads indicated that the
      response was predominantly surface positive and crossed. Control experiments
      eliminated eye movement and somatosensory input as explanations of the evoked
      response, thereby identifying it as a cortical response. The surface positive
      wave in humans was compared with the responses recorded in cat and monkey to
      cerebellar stimulation. The responses in humans could reflect dysfacilitation
      through MC activation of Purkinje cells, or feed-forward facilitation through
      transsynaptic or antidromic activation of dentate neurons. The latency of the
      surface positive wave exceeds that of cerebellar inhibition of MC elicited hand
      muscle responses, but the discrepancy is at least partly accounted for by the
      extra delay required to set up the indirect cortico-spinal component required for
      motoneuron discharge. Estimates made of the cerebello-frontal cortical and
      peripheral feedback loop times suggest that the central has less than one quarter
      the delay of the peripheral loop, which would be especially advantageous during
      fast skilled movements of the fingers.

PMID- 1380915
TI  - Inhibitory period following motor potentials evoked by magnetic cortical
      stimulation.
AB  - Following motor potentials evoked (MEPs) by magnetic cortical stimulation, there
      is a transient suppression of muscle action potentials (inhibitory period). We
      recorded MEPs, the inhibitory period, V1 waves and F waves from the abductor
      pollicis brevis muscle in 20 normal subjects and in 17 patients with spastic
      hyperreflexia due to cerebral infarction. The duration of the inhibitory period
      increased in correspondence with increasing stimulus intensity and did not
      necessarily depend on the amplitude of the MEPs. The duration of the inhibitory
      period elicited by a twin coil, which can stimulate the motor cortex locally, was
      shorter than by a single coil. The mean duration of the inhibitory period was
      significantly shorter in patients with spastic hyperreflexia than in normal
      subjects, and it correlated with the amplitude of F waves. The effects of the
      inhibitory period on V1 waves were different from its effects on F waves in one
      patient with large V1 and F waves. The amplitudes of V1 waves recorded during the
      inhibitory period were approximately 30-50% of the maximal amplitude of V1 waves,
      but F waves were not smaller. The inhibitory period is probably caused primarily
      by central inhibitory mechanisms.

PMID- 1380916
TI  - Analysis of the coil generated impulse noise in extracranial magnetic
      stimulation.
AB  - An intense impulse noise artifact is generated by the coil used in extracranial
      magnetic stimulation (EMS) of the brain and cranial nerves. In this study we
      measured and analyzed the sound pressure level (SPL), spectral content, wave
      form, and time course of the magnetic coil acoustic artifact (MCAA) impulse noise
      in the sound field and in the ear canal of life-size models of the human cranium.
      Two different clinical magnetic stimulators and coils were used. Sound field
      measurements from both coils showed the MCAA to be a transient impulse noise with
      a rapid rise-time, brief duration, broad acoustic spectrum, and high intensity.
      Measurements made on models of the human head with the magnetic coils positioned
      at selected standard clinical positions for EMS, particularly the peripheral
      facial nerve, auricle and mastoid areas, indicated that the MCAA may reach sound
      pressure levels that exceed noise damage-risk criteria limits for sensorineural
      hearing loss. The maximum peak energy in the acoustic spectrum of the MCAA
      measured in the ear canal of the model heads was from 2 to 5 kHz, the range of
      highest sensitivity in human ears. Ear protectors were found to attenuate the SPL
      of the MCAA, reaching the ear canal of the model heads by 15-22 dB SPL, and were
      recommended for use by patients and subjects exposed to EMS.

PMID- 1380917
TI  - Activated human T lymphocytes express albumin binding proteins which cross-react
      with alpha-fetoprotein.
AB  - The kinetics of iodinated human serum albumin ([125I]Hu-SA) and alpha-fetoprotein
      ([125I]Hu-AFP) binding and endocytosis by resting and phytohemagglutinin (PHA)
      activated human T lymphocytes were studied comparatively. The binding of both SA
      and AFP appeared considerably increased upon blastic transformation. SA, like
      AFP, binds in a saturable way to the surface of PHA-stimulated human T
      lymphocytes at 4 degrees C and is endocytosed at 37 degrees C. Two saturation
      plateaus were observed by incubating at 4 degrees C activated T lymphocytes with
      [125I]Hu-AFP at different concentrations (10 ng-250 micrograms/ml), while only
      one saturation plateau was obtained by incubating cells with [125I]Hu-SA in the
      same conditions. Scatchard analysis of binding data revealed two types of binding
      sites for Hu-AFP and one for Hu-SA. Competition experiments using proteins of
      human and bovine origin are in favor of the presence on the surface of these
      cells of a common binding site for AFP and SA. Pulse-chase experiments showed
      that internalized [125I]SA was released mainly in a degraded form from the cells,
      in agreement with detection by ultrastructural cytochemistry of peroxidase
      conjugated SA in lysosome-like bodies by ultrastructural cytochemistry. This
      contrasts with the intracellular pathway of AFP, which as previously described
      (Geuskens, M., et al., Eur. J. Cell Biol. 50, 418-427 (1989)), moves to tubular
      vesicular structures in the Golgi region and is recycled for the most part
      undegraded.

PMID- 1380918
TI  - Characterization of human cytokeratin 2, an epidermal cytoskeletal protein
      synthesized late during differentiation.
AB  - Among the more than 30 different human proteins of the cytokeratin (CK) group of
      intermediate filament (IF) proteins, the significance of the epidermal
      polypeptide CK 2 (Moll et al., 1982, Cell 31, 11-24) has been repeatedly
      questioned in the literature. Here, we show, by in vitro translation and protein
      gel electrophoresis, that human epidermis from various body sites does indeed
      contain relatively large amounts of mRNA encoding a distinct polypeptide
      comigrating with native epidermal CK 2. We also report the isolation of a cDNA
      clone encoding the complete sequence of CK 2, which is a type II CK different
      from--but related to--epidermal CKs 1 and 5 on the one hand and corneal CK 3 on
      the other. The mRNA of approximately 2.6 kb encodes a polypeptide of 645 amino
      acids and M(r) 65,852, in good agreement with the value of 65.5 kDa previously
      estimated from gel electrophoresis. This human CK, the largest so far known,
      displays several features typical of CKs of stratified epithelia, including
      numerous repeats of glycine-rich tetrapeptides in the head and tail domains.
      Northern blot and in situ hybridizations have shown that CK 2 is expressed
      strictly suprabasally, usually starting in the third or fourth cell layer of
      epidermis, and this was confirmed at the protein level by immunohistochemistry
      using CK 2-specific antibodies. The protein has been detected as a regular
      epidermal component in skin samples from different body sites, albeit as a minor
      CK in "soft skin" (e.g., breast nipple, penile shaft, axilla), but not in
      foreskin epithelium and in other epithelia, in squamous metaplasias and
      carcinomas, or in cultured cell lines derived therefrom. We propose that CK 2 is
      a late cytoskeletal IF addition synthesized during maturation of epidermal
      keratinocytes which probably contributes to terminal cornification.

PMID- 1380919
TI  - Regulation of U3 snRNA expression during myoblast differentiation.
AB  - Differentiation of proliferating rat L6 myoblasts to syncytial multinucleated
      myotubes results in a significant downshift in the rate of U3 snRNA gene
      transcription, paralleling the decrease in rRNA synthesis previously documented.
      Coordinate production of U3 snRNA and rRNA during the differentiation process
      adds further support for a role of U3 snRNA in ribosome biogenesis. Despite the
      dramatic decrease in U3 snRNA transcription during differentiation, a
      corresponding drop in the cellular level of U3 snRNA does not occur. In myotubes,
      the amount of U3 snRNA is regulated at the post-transcriptional level in which
      there is a significant accumulation of U3 snRNA in the cytoplasm of myotubes.
      This intracellular redistribution of U3 snRNA may significantly affect the entire
      process of rRNA maturation or result from the decrease in ribosome production
      accompanying terminal differentiation of myoblasts.

PMID- 1380920
TI  - Hypomethylation of human heterochromatin detected by restriction enzyme nick
      translation.
AB  - Using the restriction enzymes MspI and HpaII in the nick translation procedure it
      has been shown that decondensation of the paracentric heterochromatin of
      chromosome 9 during human spermatogenesis is associated with hypomethylation of
      the DNA sequences in this domain. Somatic cells treated with 5'-azacytidine also
      showed decondensation of centromeric heterochromatin. In this instance, however,
      hypomethylation is detected both in the extended heterochromatin at the
      centromeres and in the euchromatin of the chromosome arms.

PMID- 1380921
TI  - Protein kinase C associates with intermediate filaments and stress fibers.
AB  - The subcellular distribution of protein kinase C (PKC) was determined by
      immunofluorescence using anti-PKC monoclonal antibodies (MAbs). The antibodies
      used were: (1) 1.9 MAb that is directed against an epitope in the catalytic
      domain of PKC, (2) 1.3 MAb that recognizes an isozyme of PKC (Mochly-Rosen, D.,
      and Koshland, D. E., 1987, J. Biol. Chem. 262, 2291-2297; Mochly-Rosen, D., et
      al. 1987 Proc. Natl. Acad. Sci. USA 84, 4660-4664) and (3) MC-2a MAb that is
      directed against the beta-isozyme of PKC (Usuda, N., et al. 1991, J. Cell Biol.
      112, 1241-1247). The cells used in this study were baby hamster kidney cells,
      vimentin+ and vimentin- clones of SW13 (a human adrenal carcinoma cell line), CEM
      (a human T cell line), U937 (a histiocytic myeloid cell line), and HL60 (a
      promyelocytic leukemia cell line). The 1.9 MAb was found to recognize a variety
      of subcellular components, viz., nucleus (nucleoplasm and nucleolus), cytoplasm,
      vimentin-type intermediate filaments (IF), stress fibers, and cell membrane.
      Among these components the beta-isozyme-specific MAbs (1.3 and MC-2a) recognized
      only the IF network, stress fibers, and edges of the cell membrane. Experiments
      with vimentin+ and vimentin- mutants of SW13 cells, double indirect
      immunofluorescence studies with anti-vimentin and anti-PKC antibodies, and drug
      studies confirmed that the IF network is the predominant cytoskeletal network
      labeled with all anti-PKC MAbs. Immunoblotting studies with the MC-2a MAb
      revealed that the observed staining of the IF network was not due to a cross
      reaction of the MAb with IF proteins and that the MAb specifically recognizes
      PKC. These studies, while identifying the diverse cell components to which PKC
      binds, have demonstrated, for the first time, that PKC associates with the IF
      network in a variety of cell types. Additionally, the studies have confirmed the
      studies by others concerning the association of PKC with stress fibers.

PMID- 1380922
TI  - Scattering of the silver-stained proteins of nucleolar organizer regions in
      Ishikawa cells by actinomycin D.
AB  - Scattering of the silver-stained proteins of nucleolar organizer regions (Ag-NOR
      proteins) was produced by actinomycin D in Ishikawa cells. Scattering of Ag-NOR
      proteins was found only in cells treated with actinomycin D and various other
      agents had no effect. Scattering was dose-dependent up to 10(-2) micrograms/ml of
      actinomycin D, but it was not found at higher concentrations that caused marked
      inhibition of total DNA and RNA synthesis. Actinomycin D (10(-2) micrograms/ml)
      caused the following changes: (i) nucleolar segregation and (ii) emergence of
      dense fibrillar bodies in the nucleoplasm. Ag-NOR proteins were observed on the
      fibrillar centers and surrounding fibrillar components in control nucleoli, on
      the fibrillar and amorphous zones in segregated nucleoli, and on the dense
      fibrillar bodies emerging in the nucleoplasm. The scattering of Ag-NOR proteins
      was due to the argyrophilic nature of the dense fibrillar bodies. Actinomycin D
      (10(-1) micrograms/ml) also caused similar morphological alterations in the
      nucleolus and nucleoplasm, but Ag-NOR proteins were observed only on nucleolar
      remnants.

PMID- 1380923
TI  - Reduction in heat shock gene expression correlates with increased
      thermosensitivity in senescent human fibroblasts.
AB  - The expression of three major classes of heat shock genes was examined in human
      diploid cells at differing in vitro ages. Metabolic labeling of cellular proteins
      following a brief heat shock showed that the synthesis of heat shock proteins was
      significantly reduced in late-passage cells. Northern blot analyses revealed that
      the reduced expression of heat shock proteins in old cells correlated with a
      reduced accumulation of heat shock-specific transcripts. The attenuation of heat
      shock gene activity in senescent cells was not unique to thermal stress since
      exposure of cells to sodium arsenite (10-50 microM) elicited a similar response.
      The reduced expression of heat shock gene products correlated with an increased
      thermal lability in late-passage cells following acute hyperthermic (49 degrees
      C) exposure. The preinduction of heat shock genes protected cells against the
      lethal effects of acute hyperthermia and abolished the increased thermal lability
      observed in senescent cells. The reduced expression of the heat shock response
      demonstrates that old cells possess a diminished ability to withstand adverse
      environmental conditions and maintain homeostasis.

PMID- 1380925
TI  - Parental imprinting of the human H19 gene.
AB  - It has only recently become clear that genetic imprinting plays an important role
      in human embryogenesis and in processes leading to the development of pediatric
      cancers and other human diseases. Using a unique human tissue, the androgenetic
      complete hydatidiform mole, we established that the maternally inherited allele
      of the imprinted H19 gene is expressed. Our results also show that the paternal
      allele of the human IGF-II gene, a gene suspected to be parentally imprinted in
      humans, is expressed.

PMID- 1380924
TI  - Absence of PDGF-induced, PKC-independent c-fos expression in a chemically
      transformed C3H/10T1/2 cell clone.
AB  - The effect of platelet-derived growth factor (PDGF) on c-fos mRNA transcription
      was studied in the immortalized mouse embryo fibroblast C3H/10T1/2 Cl 8 (10T1/2)
      cells and the chemically transformed, tumorigenic subclone C3H/10T1/2 Cl 16 (Cl
      16). In the 10T1/2 cells as well as the Cl 16 subclone, the dose-dependent PDGF
      stimulation of c-fos mRNA synthesis was similar in both logarithmically growing
      and confluent cultures. c-fos mRNA was induced severalfold by 12-O
      tetradecanoylphorbol-13-acetate (TPA) in both 10T1/2 and Cl 16. Down-regulation
      of protein kinase C (PKC) activity by TPA pretreatment inhibited PDGF-stimulated
      c-fos mRNA expression in Cl 16 cells but did not affect this induction in the
      10T1/2 cells. This inhibition was not a general phenomenon of 3
      methylcholanthrene-mediated transformation of 10T1/2 cells since experiments with
      another transformed 10T1/2 cell clone, C3H/10T1/2 TPA 482, gave qualitatively the
      same results as the 10T1/2 cells. Receptor binding experiments showed that the
      nontransformed and transformed cells had a comparable number of PDGF receptors,
      1.3 x 10(5) and 0.7 x 10(5) receptors per cell, respectively. Furthermore, cAMP
      induced c-fos expression induced by forskolin is formerly shown to be independent
      of PKC down-regulation. In our experiments, forskolin induced c-fos expression in
      both clones. However, PKC down-regulation inhibited the forskolin-induced c-fos
      expression in Cl 16 cells. This apparently demonstrates cross talk between PKC
      and PKA in the c-fos induction pathway. The present results provide evidence for
      an impaired mechanism for activating c-fos expression through PKC-independent,
      PDGF-induced signal transduction in the chemically transformed Cl 16 fibroblasts
      compared to that in nontransformed 10T1/2 cells.

PMID- 1380926
TI  - The jasmonate precursor, 12-oxo-phytodienoic acid, induces phytoalexin synthesis
      in Petroselinum crispum cell cultures.
AB  - The pentacyclic biosynthetic precursor of jasmonic acid, 12-oxo-phytodienoic
      acid, was found to induce synthesis of the major flavonoid, apiin, in cell
      suspension cultures of Petroselinum crispum. The accumulation of apiin was
      preceded by an increase in the relative levels of poly (A)+ RNAs that code for
      the flavonoid biosynthetic enzymes phenylalanine ammonia lyase, 4-coumarate:CoA
      ligase and chalcone synthase, Poly (A)+ RNAs reached maximal levels at
      approximately 4-6 h after the addition of elicitor while flavonoids continued to
      accumulate in the cultures for at least 6 days. 12-Oxo-phytodienoic acid is the
      first pentacyclic precursor in the jasmonic acid biosynthetic chain which
      functions as a signal transducer for phytoalexin induction.

PMID- 1380927
TI  - Receptor-binding regions in human glycoprotein hormones.

PMID- 1380928
TI  - Polyclonal antibodies against the polypeptide and carbohydrate epitopes of
      recombinant human choriogonadotropin beta-subunit.
AB  - In our previous paper (Chen et al. (1991) J. Biol. Chem. 266, 4081-4087) we
      reported the preparation and characterization of recombinant human
      choriogonadotropin beta subunit (hCG beta) using the baculovirus-insect cell
      expression system. The rhCG beta was found to contain high mannose type N-linked
      carbohydrates and 3-4 serine-linked disaccharide chains. Despite the carbohydrate
      structural variation, the rhCG beta was similar to hCG beta in in vitro
      immunological and biological properties. In order to evaluate its in vivo
      immunological properties, rabbit antiserum against rhCG beta was produced. The
      antiserum was found to be almost identical to anti-hCG beta in binding to hCG
      beta as well as in its crossreactivity with human lutropin (hLH), hCG and human
      follitropin (hFSH) as indicated by radioimmunoassays using 125I-hCG beta as a
      tracer. Further characterization of the anti-rhCG beta antiserum revealed that
      there are three types of antibodies in terms of antigenic specificity present in
      the anti-rhCG beta antisera pool as shown by dot blot and radioimmunoassays. The
      carbohydrate-specific antibodies were separated by affinity chromatography using
      an ovalbumin-glycopeptide-Sepharose column. The antibodies held on the ovalbumin
      affinity adsorbent were specific for the high mannose type carbohydrates such as
      those present in rhCG beta, rhCG and thyroglobulin and failed to react with
      transferrin, alpha 1-acid glycoprotein and hCG alpha, all containing complex type
      carbohydrates. This was further supported by the fact that the recombinant
      unglycosylated hCG or periodate oxidized rhCG beta also did not show any
      reactivity with the carbohydrate specific antibodies. Two types of peptide
      epitopes seemed to be present in rhCG beta since when the flowthrough fraction
      from the ovalbumin-glycopeptide-affinity column was passed through the hCG beta
      Sepharose column, the antibodies in the flowthrough from the latter column were
      specific to the unique antigenic determinants present only in the rhCG beta and
      not in hCG beta. The eluate from the hCG beta-Sepharose column contained the
      third type of antibodies, being the predominant ones, directed to the common
      epitopes between rhCG beta and hCG beta. The high mannose type specific
      antibodies are potentially useful in differentiating between the high mannose and
      complex type of N-linked carbohydrates present in a glycoprotein. Also, the
      antibody could provide an effective reagent in studying the intracellular
      processing of the N-linked oligosaccharides.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380929
TI  - Monoamines (serotonin and catecholamines) and their derivatives in infantile
      autism: age-related changes and drug effects.
AB  - Levels of dopamine (DA) and its derivatives homovanillic acid (HVA), 3-4
      dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3MT) and
      norepinephrine+epinephrine (NE + E), and serotonin (5HT) and its derivative 5
      hydroxyindolacetic acid (5HIAA) were determined from the urine of 156 autistic
      children aged two to 12 years 6 months, and compared with those of age-matched
      mentally retarded non-autistic and normal controls. Very significant group and
      age effects were found for DA, HVA, 3MT, NE + E and 5HT. High HVA, 3MT, NE + E
      and 5HT levels were found in autistic and non-autistic children. The DA, HVA,
      3MT, NE + E, 5HT and 5HIAA levels decreased significantly with age in the three
      groups. Significantly decreased levels of DA and HVA were observed in autistic
      children on haloperidol, compared with non-medicated autistic children. The
      results are discussed in relation to the hypothesis of a maturation defect of
      monoaminergic systems in autism.

PMID- 1380930
TI  - Intellectual and physical outcome of children undernourished in early life is
      influenced by later environmental conditions.
AB  - Thirty-five schoolchildren who share a common history of early undernutrition and
      who were reared after recovery by adoptive families (16), in institutional care
      (eight) or by their biological families (11) were assessed for physical and
      intellectual outcome. The adopted children had mean normal weight and height for
      age, but the children from institutions were significantly shorter. Adopted
      children had mean Full-scale, Verbal and Performance IQs in the normal ranges,
      with significant differences from the other two groups, mainly for the Verbal
      subscale. These results emphasize that the growth and development of early
      undernourished children are not irreversibly fixed by the acute illness, but are
      highly sensitive and modifiable by early and stable environmental improvement.

PMID- 1380931
TI  - Instability of the intelligence quotient-motor quotient relationship.
AB  - The authors evaluated the stability over one- and two-year periods of the
      relationship between a cognitive measure (McCarthy General Cognitive Index) and a
      motor measure (McCarthy Motor Scale) to examine whether the cognitive-motor
      relationship changed significantly over time and whether children remained in the
      same service eligibility category, based on the cognitive referencing model.
      Results indicated substantial changes in the cognitive-motor relationship. Over a
      two-year period, more than 42 per cent of children changed their cognitive-motor
      relationship by at least 16 points. Children's eligibility for service, based on
      the cognitive referencing model, also fluctuated substantially over time. The
      authors conclude that the cognitive referencing model of triage is not an
      effective means of determining who should receive physical and occupational
      therapy services. Alternative methods are suggested.

PMID- 1380932
TI  - Double stents for carcinoma of the esophagus invading the tracheo-bronchial tree.
AB  - Extrinsic compression, neoplastic involvement of the trachea or left main
      bronchus, and esophago-airway fistula may cause airway obstruction and infection
      in patients with esophageal carcinoma. Further reduction of airway lumen may
      result from palliative treatment of dysphagia by radiation or esophageal stent
      insertion. In order to evaluate the extent of airway compromise, bronchoscopy was
      systematically performed in 39 consecutive patients with advanced carcinoma of
      the esophagus requiring esophageal endoprostheses. Airway obstruction observed in
      10 patients (mean age, 60 years) resulted in the additional placement of a
      silicone stent in the trachea (five patients) or left main bronchus (five
      patients). Esophageal and airway procedures were performed under general
      anesthesia. All had squamous cell carcinoma of the middle third of the esophagus.
      Severe dyspnea at rest was documented in five patients prior to intervention.
      Esophago-tracheal fistula was present in five. Eight patients with associated,
      neoplastic invasion of the tracheo-bronchial tree required airway Nd:YAG laser
      therapy. The esophageal prosthesis contributed significantly to airway compromise
      in four patients. Symptomatic relief of dysphagia and dyspnea was obtained in all
      individuals. Mean survival was 121 days (range, 12 to 350 days). Complications
      were not serious, but included esophageal or tracheal stent migration in three
      patients.

PMID- 1380933
TI  - The nature of the acetylcholine receptor in a Buccinum proboscis muscle examined
      by the sucrose-gap voltage clamp technique.
AB  - 1. ACh dose-response curves for the radicular retractor muscle of Buccinum showed
      maximum force and membrane depolarisation of 3.3 mV at 50 mumol l-1 ACh. 2. PCh
      was found to be almost a full agonist for force and induced higher membrane
      depolarisations than ACh while BCh was only a partial agonist of very low
      potency. This suggests an AChR neither muscarinic nor nicotinic in mammalian
      terminology. 3. Neither muscarine nor nicotine had any direct agonistic effects
      on the muscle but pre-exposure to nicotine inhibited both force and membrane
      depolarisation induced by a subsequent dose of ACh. 4. The specific muscarinic
      and nicotinic antagonists atropine, d-tubocurarine and gallamine all inhibited
      ACh responses in a dose-dependent manner. 5. Single sucrose-gap recording showed
      that ACh induced a depolarisation resulting in a contracture. Double sucrose-gap
      voltage clamp recording showed that 10 mumol l-1 ACh induced an inward
      transmembrane current of ca 2 microA. Both ACh-induced depolarisation and inward
      current were abolished in Na-free media. 6. When clamped at a series of membrane
      voltages between natural Em and positive potentials the ACh-induced Na-dependent
      inward current declined as Em was reduced and was abolished at -10 mV. This
      current showed no reversal even at strong positive membrane voltages. 7. The AChR
      of this muscle appears to be neither exclusively nicotinic nor muscarinic but a
      hybrid and shows characteristics of voltage inactivation.

PMID- 1380934
TI  - Na+/Ca2+ exchange mediation in the ouabain-induced contraction in human placental
      vessels.
AB  - 1. Ouabain induced concentration-dependent contractions in segments of human
      placental arteries and veins, which were practically abolished in a Ca(2+)-free
      medium and not modified by the calcium antagonist nifedipine or the calcium
      agonist Bay K 8644. 2. Ouabain (10(-4) M) elicited a time-dependent enhancement
      of the 45Ca2+ uptake, which remained equal in presence of nifedipine or Bay K
      8644. 3. The Na+/Ca2+ exchange blocker amiloride reduced both the contractions
      and the 45Ca2+ uptake induced by ouabain, whereas the Na ionophore monensin
      produced a parallel shift to the left of the concentration-response curve to
      ouabain. 4. These results suggest that ouabain-induced contractions in these
      vessels are dependent on the extracellular Ca2+, which mainly enters into the
      cell through the Na+/Ca2+ exchange system.

PMID- 1380935
TI  - Effects of clonixin on the electrical activity of cardiac pacemaker cells.
AB  - 1. The electrophysiological effects of clonixin, a non-steroidal analgesic, on
      cardiac pacemaker cells of spontaneously beating frog sinus venosus, were studied
      by intracellular recording of transmembrane potentials. 2. Results show that
      clonixin (Clx) between 1 x 10(-6) M and 3 x 10(-4) M, decreases the OS, APA, Vmax
      and frequency of primary and subsidiary cells, however pacemaker cells differ in
      their sensitivity to Clx. 3. At 2 x 10(-6) M, Clx completely blocked the
      spontaneous beating of primary cells. It is necessary to increase the Clx
      concentration about two orders of magnitude in order to attain a similar degree
      of blockade of subsidiary cells. 4. Previous or simultaneous superfusion with
      atropine does not modify Clx effects, thus a probable cholinergic mechanism of
      action for Clx is discarded. 5. When Clx concentrations were lower than 5 x 10(
      4) M, their effects on both types of cells were partially reversed by a 100%
      increase of external calcium concentration. 6. BAY K-8644 which stimulates
      calcium influx through calcium L-type channels, reverted Clx effects on pacemaker
      cells. 7. It is suggested that Clx blocks calcium inward current which generates
      all or part of the upstroke of primary cells and subsidiary ones, respectively.

PMID- 1380937
TI  - Calcitonin enhances the effects of nimodipine on biogenic amines of rat brain.
AB  - 1. Nimodipine affects the brain biogenic amines suggesting both inhibition of the
      striatal dopaminergic system and activation of serotonergic systems in various
      brain areas. 2. Salmon calcitonin affects serotonergic systems as nimodipine
      does. 3. It was hypothesized that these effects could be more than additive since
      they all have been ascribed to inhibition of neuronal calcium influx. 4. Biogenic
      amines and metabolites were determined in brain areas obtained from rats
      pretreated with saline or salmon calcitonin (10 MRC U/kg, s.c.) and treated with
      nimodipine (2.5-20 mg/kg, i.p.). 5. The effects of nimodipine and salmon
      calcitonin appeared to be merely additive.

PMID- 1380936
TI  - Differential effect of calcium and Bay K 8644 on the inhibitory action of
      estrogens in the rat uterus.
AB  - 1. The effects of the estrogens estradiol (E2, 10(-7) to 3 x 10(-5) M) and
      diethylstilbestrol (DES, 10(-7) to 3 x 10(-6) M) on tonic contractions of the rat
      uterus induced by KCl and CaCl2 have been studied. 2. E2 and DES relaxed, in a
      dose-dependent way, the tonic contraction induced by KCl (60 mM) (IC50: 5.16 +/-
      1.49 x 10(-6) and 4.51 +/- 0.03 x 10(-7) M); the tonic contraction induced by
      CaCl2 (3 mM) in the rat uterus incubated in depolarizing Krebs (127 mM of K+)
      have also been relaxed (IC50: 8.6 +/- 0.03 x 10(-7) and 2.56 +/- 0.07 x 10 M) by
      both drugs. 3. The CaCl2 (0.1 to 10 mM) counteracted the relaxing effect of E2
      and DES, respectively, up to 28.13 +/- 10.2% and 34.71 +/- 11.5%, on KCl-induced
      contractions, and up to 126.36 +/- 19.35% and 95.8 +/- 16.3% on CaCl2-induced
      contractions. 4. Bay K 8644 (10(-10) to 10(-6) M) reversed the relaxing effect of
      E2 and DES, respectively, up to 42.49 +/- 2.28% and 43.31 +/- 3.59% on KCl
      induced contractions, and up to 21.73 +/- 4.16% and 75.97 +/- 9.63% on CaCl2
      induced contractions. 5. Propranolol (10(-6) M) did not modify the relaxing
      effect of E2 or DES on CaCl2-induced contractions.

PMID- 1380938
TI  - The differential staining pattern of the X chromosome in the embryonic and
      extraembryonic tissues of postimplantation homozygous tetraploid mouse embryos.
AB  - (C57BL x CBA)F1 hybrid female mice were mated with hemizygous Rb(X.2)2Ad males to
      distinguish the paternal X chromosome. Homozygous tetraploids were produced by
      blastomere fusion at the 2-cell stage, and 161 of these were transferred to
      recipients and analysed on the 10th day of gestation. 59 implants contained
      resorptions and 76 contained either an embryo and/or extraembryonic membranes. 38
      (20, XXXX and 18, XXYY) were analysed to investigate their X-inactivation
      pattern. Embryonic and yolk sac endodermally- and mesodermally-derived samples
      were analysed by G-banding and by Kanda analysis. In the XX and XY controls, the
      predicted pattern of X-inactivation was observed, though 12.2% of metaphases in
      the XX series displayed no X-inactivation. In the XY series the Y chromosome was
      seen in a high proportion of metaphases. In the XXXX tetraploids, 8 cell lineages
      were recognized with regard to their X-inactivation pattern, though most belonged
      to the following 3 categories: (XmXm)XpXp, Xm(XmXp)Xp and XmXm(XpXp). The other
      categories were only rarely encountered. In the embryonic and mesodermally
      derived tissue the ratio of these groups was close to 1:2:1, whereas in the
      endodermally-derived tissue it was 1:4.11:4.88, due to preferential paternal X
      inactivation. A significant but small proportion of all 3 tissues analysed
      displayed no evidence of X-inactivation. Indirect evidence suggests that this
      represents a genuine group because of the high efficiency of the Kanda staining.
      The presence of the Xm(XmXp)Xp category is consistent with the expectation that X
      inactivation occurs randomly in 2 of the 4 X chromosomes present. The presence of
      small numbers of preparations with no evidence of X-inactivation and other
      unexpected categories suggests that these are probably selected against during
      development.

PMID- 1380939
TI  - Expression of heterologous peptides at two permissive sites of the MalE protein:
      antigenicity and immunogenicity of foreign B-cell and T-cell epitopes.

PMID- 1380940
TI  - Identification of a repetitive element in the snail Biomphalaria glabrata:
      relationship to the reverse transcriptase-encoding sequence in LINE-1
      transposons.
AB  - BamHI-digested Biomphalaria glabrata DNA contains a repetitive 2.0-kb fragment
      which is readily discernible by ethidium bromide staining. We present evidence
      that this repetitive element is related at both the nucleotide and amino acid
      levels to long interspersed nuclear element (LINE)-like transposons. Although
      comparable elements have been described in several invertebrates, this is the
      first report of a molluscan homologue. In common with LINE transposons, an open
      reading frame in the B. glabrata element shows significant homology to reverse
      transcriptase--a feature believed to allow the dissemination of these elements in
      the eukaryotic genome.

PMID- 1380941
TI  - Prostate specific antigen: clinical use in the diagnosis and management of
      prostate cancer.
AB  - Prostate specific antigen (PSA) has replaced prostatic acid phosphatase as the
      preeminent clinical tumor marker in the management of patients with prostate
      cancer. Serum PSA levels have been shown to be proportional to clinical and
      pathologic stage of prostate cancer and in particular to correlate closely with
      prostate cancer volume. Serum levels of PSA thus serve as a useful adjunct in the
      initial clinical staging of men with prostate cancer. Serum PSA values provide a
      unique and valuable tool in monitoring prostate cancer progression over time and
      its response to surgical, radiation, and/or hormonal therapies. Unfortunately,
      its lack of specificity for prostate cancer leaves many questions unanswered as
      to the efficacy and advisability of using PSA as a screening test for this
      cancer.

PMID- 1380942
TI  - Omission of exon 12 in cystic fibrosis transmembrane conductance regulator (CFTR)
      gene transcripts.
AB  - Cystic fibrosis transmembrane conductance regulator (CFTR) mRNA transcripts
      isolated from both expressing and "non-expressing" cell types of normal
      individuals exhibit differential splicing to a variable extent in a region
      encoding the putative nucleotide binding fold of the CFTR polypeptide. Sequence
      analysis of the aberrant fragments obtained after cDNA polymerase chain reaction
      amplification confirmed the in-frame joining of exons 11 and 13. The proportion
      of alternative splicing is reproducible and constant in a given individual. The
      omission of exon 12 in a significant proportion of transcripts supports the
      hypothesis that a minimal amount of correctly expressed CFTR is sufficient for
      the maintenance of a clinically normal phenotype.

PMID- 1380943
TI  - Incidence and expression of the N1303K mutation of the cystic fibrosis (CFTR)
      gene.
AB  - The N1303K mutation was identified in the second nucleotide binding fold of the
      cystic fibrosis (CF) gene last year. We have gathered data from laboratories
      throughout Europe and the United States of America in order to estimate its
      frequency and to attempt to characterise the clinical manifestations of this
      mutation. N1303K, identified on 216 of nearly 15,000 CF chromosomes tested,
      accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele
      varies significantly between countries and ethnic groups, being more common in
      Southern than in Northern Europe. This variation is independent of the delta F508
      allele. It was not found on UK Asian, American Black or Australian chromosomes.
      N1303K is associated with four different linked marker haplotypes for the
      polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for
      this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in
      the other CF allele. We classify N1303K as a "severe" mutation with respect to
      the pancreas, but can find no correlation between this mutation, in either the
      homozygous or heterozygous state, and the severity of lung disease.

PMID- 1380944
TI  - Relationships between %Hb F or %G gamma and the haplotypes in the beta-globin
      gene cluster in the normal adult Japanese and Korean populations.
AB  - Haplotypes or subhaplotypes in the beta-globin gene cluster were examined in 31
      normal Japanese and 21 Korean families. Major haplotypes were VII, V, and I,
      which shared a common subhaplotype [+----], and occurred in 70% of the Japanese
      and 68% of the Koreans. Three haploypes which shared a common subhaplotype [-+
      ++], bearing the XmnI site 5' to the G gamma-globin gene, occurred in 13% of the
      Japanese and 7.3% of the Koreans. One subhaplotype [-++-+], which is closely
      linked to the A gamma T-globin gene, had an incidence of 6.6% in the Japanese and
      20% in the Koreans. Rare subhaplotypes [---++], and [- +] which has been observed
      mainly in Melanesians and Polynesians, and a very rare subhaplotype [-----] were
      observed. The present study suggests that high or low G gamma-globin chain
      production is closely related to subhaplotypes [-+-++] and [+----], respectively,
      among the normal adult population.

PMID- 1380945
TI  - %Hb A2, %Hb F, %G gamma values and the haplotypes in the beta-globin gene cluster
      in Japanese adults with elevated Hb F.
AB  - The percentages of minor adult hemoglobin (%Hb A2) in hemolysates and G gamma
      globin chain (%G gamma) in fetal Hb (Hb F) of 15 individuals with elevated Hb F
      levels (2.0-11%) among 11,000 healthy Japanese adults were examined. Most of them
      might be carriers for the determinants of hereditary persistence of fetal
      hemoglobin. Subjects with less than 1.3% Hb A2, some of whom might be also
      carriers for delta-thalassemia determinants, had high G gamma values (54-70%).
      Those homozygous for a subhaplotype [+-----] 5' to the delta-globin gene had low
      to mid G gamma values (7-49%), while those homozygous for [-++-++] possessed high
      G gamma values (60-85%), but varied Hb F values (3.1-11%). Those heterozygous for
      the presence of the XmnI site 5' to (-158 bp to the cap site of) the G gamma
      globin gene had mid to high G gamma values (53-65%). Factors for the high or low
      G gamma-globin gene expression in the Japanese adult with elevated Hb F level
      should be highly associated with a subhaplotype [-++-++] or [+-----],
      respectively.

PMID- 1380946
TI  - The XmnI site 5' to the G gamma-globin gene polymorphism and its relationship to
      %Hb F and %G gamma in normal Japanese and Korean adults.
AB  - The ratio of fetal hemoglobin to total hemoglobin (%Hb F), the ratio of G gamma
      to total gamma globin (%G gamma), and the polymorphism of the XmnI site at -158
      base pairs from the cap site of the G gamma-globin gene were examined in normal
      unrelated Japanese (n = 113) and Korean (n = 44) adults. The frequency of the
      presence of the XmnI site was 0.15 in the Japanese and 0.16 in the Korean
      population. There were statistically significant differences in the %G gamma
      values of the Japanese between those +/+ and those +/- or -/- at the XmnI site (p
      less than 0.01). The Korean %G gamma values showed a statistically significant
      difference (p less than 0.01) between those +/- and those -/-. The presence of
      the XmnI site was significantly associated with the elevation of G gamma-globin
      chain synthesis, but this relationship was not necessarily absolute. The absence
      of the XmnI site in an adult with a gamma-globin gene triplication (G gamma AG
      gamma A gamma/G gamma A gamma) more or less reduced the level of G gamma-globin
      chain synthesis, but the presence of the XmnI site in an adult with a gamma
      globin gene deletion (GA gamma/G gamma A gamma) had no effects on the proportion
      of the two gamma-globin chains.

PMID- 1380947
TI  - Enzyme-linked immunosorbent assay for riboflavin carrier protein and modified
      protein: application for epitope analysis.
AB  - Rabbit antibodies to native riboflavin carrier protein (RCP), are to a large
      extent directed towards the conformational epitopes and antibodies to disulphide
      bond reduced carboxymethylated riboflavin carrier protein (RCM-RCP) to the
      sequential epitopes. Taking advantage of this premise and in order to map the
      epitopes of RCP recognized by the antibodies, enzyme-linked immunosorbent assays
      were validated for RCP and RCM-RCP using the Avidin-Biotin system. The usefulness
      of these assays were illustrated when antigenicity of peptides derived from RCM
      RCP following trypsinization were examined. Two major (T1,T2) and one minor
      peptide (T3) fractions were obtained when the tryptic peptides were fractionated
      on DEAE-cellulose. RCP has a blocked N-terminal. Tryptic peptides (T1 and T2) on
      microsequencing revealed the absence of an N-terminal amino acid, indicating that
      these fragments emanate from the N-terminal region of RCP. In support of this
      observation is the finding that antipeptide antibody to cRCP (10-24) of cRCP
      interacted with T1 as well as T2 indicating the presence of the sequential
      epitope (10-24) of cRCP in these fragments. In RCP-ELISA, only T2 displaced RCP
      and peptides T1 and T2 displaced RCM-RCP in RCM-RCP ELISA. Differences in the
      ability of these fragments (T1 and T2) to displace RCP and RCM-RCP reflect the
      subtle changes in the spatial structures of these epitopes in RCP and RCM-RCP.

PMID- 1380948
TI  - Hormonal modulation of biosynthesis of prostatic specific antigen, prostate
      specific acid phosphatase and prostatic inhibin peptide.
AB  - Hormonal modulation of in vitro biosynthesis of three prostatic secretory
      proteins, prostate specific acid phosphatase (PSAP), prostate specific antigen
      (PSA) and prostatic inhibin peptide (PIP) by human benign hyperplasia (BPH)
      tissue was studied. LH and inhibins caused increase in the synthesis of all three
      proteins whereas FSH enhanced the synthesis of PIP and PSA only but decreased
      PSAP synthesis. Prolactin and thyroid releasing hormone decreased synthesis of
      PIP and PSAP. However, PSA synthesis was enhanced by TRH and was decreased by
      prolactin. Estradiol caused significant increase in PSA and PSAP but no
      discernible changes in PIP synthesis were noticed. Testosterone caused an
      increase in PIP, PSA and PSAP. These data indicate that biosynthesis of PIP, PSA
      and PSAP by BPH tissue is under multihormonal regulation.

PMID- 1380949
TI  - Amoeboid and ramified microglia: their interrelationship and response to brain
      injury.
AB  - Rio-Hortega's hypothesis that transiently appearing amoeboid microglia might
      become ramified microglia in the adult and that the latter could differentiate
      into brain macrophages in the event of brain damage could not be proved because
      of inherent limitations in existing techniques. The present investigation used a
      novel method of labelling the rat supraventricular amoeboid microglia with an
      enduring fluorescent marker, rhodamine B isothiocyanate, introduced
      intraperitoneally. Observation of their subsequent development showed that they
      became transformed into the ramified microglia. Both the amoeboid and ramified
      microglia were OX-42 positive, indicating their macrophage/monocyte lineage.
      Other microglia in the cerebral neocortex, which were also OX-42 positive, were
      not derived from any of the rhodamine-labelled cells. Rhodamine-labelled
      microglia did not migrate toward the site of a superficial cerebral injury.
      Following a deep lesion reaching the corpus callosum, greatly increased numbers
      of labelled amoeboid microglia were frequently observed at or near the lesion
      site. Large rhodamine-labelled cells, which were OX-42 positive, appeared at all
      lesioned sites, and such were most likely blood derived monocytes. The
      antigenicity of the ramified microglia became elevated when rhodamine B
      isothiocyanate was present intracellularly and even more so with the presence of
      a nearby intracerebral stab wound.

PMID- 1380950
TI  - Changes of host cell infiltration into Meth A fibrosarcoma tumor during the
      course of regression induced by injections of a BCG nucleic acid fraction.
AB  - MY-1, which consists of DNA and RNA extracted and purified from Mycobacterium
      bovis strain BCG, causes the regression of various experimental syngeneic tumors
      when injected intratumorally. In order to identify the host cells involved in the
      antitumor mechanism(s) of MY-1, we examined Meth A tumors inoculated
      intradermally to BALB/c mice, which were given multiple injections of MY-1
      following tumor inoculation. Histological and immunohistochemical examinations
      were performed at several time points. On day 4 after inoculation, the MY-1
      treated tumors were heavily infiltrated with a heterogeneous population of
      mononuclear cells with low density nuclei. The MY-1-injected tumors contained
      asialo-GM1-positive cells and Mac-1-positive cells, which indicated that the
      infiltrating mononuclear cells were natural killer cells and macrophages. On day
      14 after inoculation, the tumors were infiltrated with a large number of L3T4
      positive cells and fewer Lyt-2-positive cells, both of which were more abundant
      in the MY-1-treated tumors than in the control tumors. The observed sequence of
      host cell infiltration corresponded well with our previous studies which have
      indicated that the antitumor mechanism of MY-1 is divided into two phases, i.e.
      the early phase when natural killer cells and macrophages inhibit tumor growth,
      and the late phase when L3T4-positive cells act to induce tumor regression via a
      delayed-type hypersensitivity against tumor cells.

PMID- 1380951
TI  - The effects of the antifungal azoles itraconazole, fluconazole, ketoconazole and
      miconazole on cytokine gene expression in human lymphoid cells.
AB  - The antifungal azole drugs itraconazole (itra; R51,211), fluconazole (flu; UK
      49,858), ketoconazole (keto) and micronazole (mico) have been investigated for
      their suppressive influence on the gene expression of the immunoregulatory
      cytokines IL2, IL4, IL9, GM-CSF, TNF-alpha, IFN-gamma, as well as both chains of
      the IL2 receptor in human PBMC and of the cytokines in the human keratinocyte
      cell line HaCat 17.5. The results obtained in Northern blot analysis were
      compared with the effects of the established immunosuppressant drug CSA and the
      new immunosuppressive drug FK 506, as well as the cytokine TGF-beta, which is
      also immunosuppressive. While 1 microgram/ml CSA and 0.1 microgram/ml FK 506
      completely suppressed PHA-stimulated accumulation of mRNA for IL2, IL4, IL9, GM
      CSF, TNF-alpha and IFN-gamma in PBMC, flu, keto and TGF-beta failed to inhibit
      any (except TNF-alpha blocked by TGF-beta). Itra and mico did suppress
      accumulation of mRNA, but unlike CSA and FK 506, only at high doses (10
      micrograms/ml) and after extended incubation (24 h). None of the drugs nor TGF
      beta suppressed the expression of the IL2R-alpha and IL2R-beta genes or TNF-alpha
      stimulated cytokine gene expression in keratinocytes. Itra and mico, 1 mg/ml
      (achievable serum level), caused only slight inhibition of the cytokines in PBMC
      after 6 and 24 h of incubation. These results demonstrate that the mode of action
      of the azoles is different from CSA and FK 506.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380952
TI  - Fibrinolysis activity promotes tumor invasiveness of B16 melanoma cell lines
      through a reconstituted gel matrix.
AB  - We studied the role of the fibrinolytic function in the invasiveness of murine
      melanoma B16F1 and F10 cells using a reconstituted matrix on a filter in a
      modified Boyden chamber. The main species of plasminogen activators (PAs)
      synthesized in cell lysates and released into conditioned media by these cells
      was found to be tissue-type PA (t-PA). The invasiveness of these cell lines was
      enhanced by adding plasminogen to the gel matrix. This enhancing effect of
      plasminogen was markedly suppressed by adding anti-t-PA IgG and plasmin
      inhibitors into the gel matrix, but less affected by anti-urokinase-type PA (u
      PA) IgG, offering more evidence to the hypothesis that the activation of the
      fibrinolytic system by PAs plays an important role in the invasiveness of murine
      melanoma B16 cell lines, and indicating that t-PA contributed more than u-PA to
      the invasive potential of these cells into the pericellular matrix.

PMID- 1380953
TI  - Restoration with phorbol ester of a locomotor defect in human leukaemic
      lymphocytes: a visual study of chronic lymphocytic leukaemia cells.
AB  - Visual assays were used to study the effect of phorbol myristate acetate (PMA) on
      the locomotion of lymphocytes from 14 patients with chronic lymphocytic leukaemia
      (CLL). Previous reports had shown that CLL cells from blood were defective in
      locomotor capacity and that adding PMA to the cells did not restore locomotion in
      a short-term (30 min) assay, but did stimulate unusual non-locomotor, multipolar,
      morphologies in a small proportion of the cells. Here we describe experiments in
      which CLL cells were cultured for 48 h in PMA. Many of the cells acquired
      locomotor morphologies with front-tail polarity which was unlike the short-term
      multipolar morphology. These cultured cells were also capable of locomotion and
      invaded collagen gels. Autoradiography suggested that after culture in PMA, the
      locomotory cells were the most active cells in 3H-uridine uptake. A computer
      analysis suggested that the cells in locomotor morphology were the same cells
      that increased in size. These findings suggest that, to acquire locomotor
      capacity, CLL lymphocytes require an appropriate signal to allow the cells to
      enter the cell cycle. During G1 the lymphocytes develop the capacity for
      locomotion. Long-term, but not short-term, culture in PMA provides such a signal
      but the mechanism by which it does so is unclear.

PMID- 1380954
TI  - Gamma-aminobutyric acidA receptor structure and function.

PMID- 1380956
TI  - Primary sequence and functional expression of a novel ouabain-resistant Na,K
      ATPase. The beta subunit modulates potassium activation of the Na,K-pump.
AB  - In order to understand the molecular mechanism of ouabain resistance in the toad
      Bufo marinus, Na,K-ATPase alpha and beta subunits have been cloned and their
      functional properties tested in the Xenopus laevis oocyte expression system.
      According to sequence comparison between species, alpha 1, beta 1, and beta 3
      isoforms were identified in a clonal toad urinary bladder cell line (TBM 18-23).
      The sequence of the alpha 1 isoform is characterized by two positively charged
      amino acids (Arg, Lys) at the N-terminal border of the H1-H2 extracellular loop
      and no charged amino acid at the C terminus, a pattern distinct from the ouabain
      resistant rat alpha 1 isoform. The coexpression of alpha 1 beta 1 or alpha 1 beta
      3 TBM subunits in the Xenopus oocyte resulted in the expression of identical
      maximum Na,K-pump currents with identical inhibition constant for ouabain (Ki)
      (alpha 1 beta 1: 53 +/- 3 microM; n = 7 vs. alpha 1 beta 3: 57 +/- 3.0 microM; n
      = 8) but distinct potassium half activation constant (K1/2) (alpha 1 beta 1: 0.87
      +/- 0.08 mM, n = 16; alpha 1 beta 3: 1.29 +/- 0.07 mM, n = 17; p less than
      0.005). We conclude that (i) the TBM alpha 1 isoform is necessary and sufficient
      to confer the ouabain resistant phenotype; (ii) the beta 3 or beta 1 subunit can
      associate with the alpha 1 equally well without affecting the ouabain-resistant
      phenotype; (iii) some specific sequence of the beta subunit can modulate the
      activation of the Na,K-pump by extracellular potassium ions.

PMID- 1380955
TI  - NH2-terminal modification of the phosphatase 2A catalytic subunit allows
      functional expression in mammalian cells.
AB  - Functional expression of recombinant wild-type phosphatase 2A catalytic subunit
      has been unsuccessful in the past. A nine-amino-acid peptide sequence (YP
      YDVPDYA) derived from the influenza hemagglutinin protein was used to modify the
      NH2 and/or COOH terminus of the phosphatase 2A catalytic subunit. Addition of the
      nine-amino-acid sequence at the NH2 terminus allowed recombinant phosphatase 2A
      expression as a predominantly cytosolic phosphatase 2A enzyme. The 12CA5
      monoclonal antibody that recognizes the nine-amino-acid hemagglutinin peptide
      sequence was used to immunoprecipitate the epitope-tagged phosphatase 2A
      catalytic subunit. Assay of the immunoprecipitated epitope-tagged phosphatase 2A
      demonstrated an okadaic acid-sensitive dephosphorylation of [32P] histone H1 and
      [32P]myelin basic protein similar to that measured with the wild-type enzyme.
      Functional phosphatase activity could be demonstrated for the NH2-terminal
      modified phosphatase 2A catalytic subunit following transient expression in COS
      cells or stable expression in Rat1a cells. In contrast, the COOH-terminal
      modified phosphatase 2A catalytic subunit was very poorly expressed. The NH2-,
      COOH-modified subunit, having the nine-amino-acid hemagglutinin peptide sequence
      encoded at both termini of the polypeptide, was also expressed as a functional
      phosphatase 2A enzyme. Thus, NH2-terminal modification of the phosphatase 2A
      catalytic subunit results in a functional plasmid-expressed enzyme. The unique
      nine-amino-acid epitope-tag sequence also provides a method to easily resolve the
      recombinant phosphatase 2A from the endogenous wild-type gene product and related
      phosphatases expressed in cells.

PMID- 1380957
TI  - Characterization of putative glycoinositol phospholipid anchor precursors in
      mammalian cells. Localization of phosphoethanolamine.
AB  - A number of mammalian cell surface proteins are anchored by glycoinositol
      phospholipid (GPI) structures that are preassembled and transferred to them in
      the endoplasmic reticulum. The GPIs in these proteins contain linear ethanolamine
      (EthN)-phosphate (P)-6ManManManGlcN core glycan sequences bearing an additional
      EthN-P attached to the Man residue (Man 1) proximal to GlcN. The biochemical
      precursors of mammalian GPI anchor structures are incompletely characterized. In
      this study, putative [3H]Man-labeled GPI precursors were obtained by in vitro GDP
      [3H] Man labeling of HeLa cell microsomes and by in vivo [3H]Man labeling of
      class B and F Thy-1 negative murine lymphoma mutants known to accumulate
      incomplete GPIs. The high performance liquid chromatography-purified in vitro and
      accumulated in vivo GPI products were structurally analyzed by nitrous acid
      deamination, hydrofluoric acid, trifluoroacetic acid hydrolysis, biosynthetic
      labeling, and exoglycosidase treatment. The data were consistent with a
      biosynthetic scheme in which Man and EthN-P are added stepwise to the developing
      glycan. Several additional points were demonstrated: 1) putative mammalian GPI
      precursors contain incomplete core glycans corresponding to those in previously
      characterized trypanosome GPI precursors. 2) The proximal EthN-P found in mature
      mammalian GPI anchor structures is added to Man 1 prior to incorporation of Man 2
      and Man 3. 3) Glycans in the incomplete GPIs that accumulate in classes B and F
      lymphoma mutants consist of Man2- and Man3GlcN in which EthN-P is linked to Man
      1. 4) Distal EthN-P linked to the 6-position of Man, characteristic of the
      complete GPI core, is found both in a subsequent GPI species with the glycan
      sequence EthN-P-6ManMan(EthN-P----)ManGlcN and in a more polar GPI product.

PMID- 1380958
TI  - Five PDGF B amino acid substitutions convert PDGF A to a PDGF B-like transforming
      molecule.
AB  - We used site-directed mutagenesis to determine the minimum number of PDGF B
      residues needed to convert PDGF A to a potently transforming PDGF B-like
      molecule. Substitution of two PDGF B subdomains, 106-115 and 135-144, were found
      to be critical. These substitutions were sufficient to broaden the ability of
      PDGF A to activate beta as well as alpha platelet-derived growth factor (PDGF)
      receptors and increase its transforming efficiency to that of PDGF B. Within
      subdomain I, either PDGF B residues Arg-109 and Asn-115 or Arg-109, Leu-110, and
      Arg-113, in combination with subdomain II PDGF B residues Asn-136, Arg-137, and
      Arg-142 were identified as being essential. Those mutants with transforming
      ability comparable with PDGF B showed significantly lower efficiencies of beta
      receptor triggering. Thus, our studies identify a small number of PDGF B amino
      acids indispensable for beta PDGF receptor interaction and suggest that a low
      level of beta PDGF receptor activation is sufficient to dramatically increase
      PDGF transforming efficiency in NIH 3T3 cells.

PMID- 1380959
TI  - Alteration of phosphotyrosine-containing proteins at the early stage of erythroid
      differentiation of mouse erythroleukemia (MEL) cells.
AB  - Following treatment of mouse erythroleukemia (MEL) cells with dimethyl sulfoxide
      and other typical erythroid inducing agents, the profile of cellular
      phosphotyrosine-containing proteins was drastically altered. We found that the
      level of almost all of the phosphotyrosine-containing proteins was either
      decreased or disappeared at a very early stage of differentiation. Addition of
      sodium orthovanadate (Na3VO4), a specific inhibitor of phosphotyrosine
      phosphatases, prevented the alteration as well as erythroid differentiation.
      Mutant MEL cells, which are resistant to differentiation by dimethyl sulfoxide,
      were apparently insensitive to the alteration. These results indicate that
      dephosphorylation of phosphotyrosine residues in cellular proteins is coupled
      with a reaction(s) which is responsible for triggering differentiation of MEL
      cells.

PMID- 1380960
TI  - The amyloid beta-protein precursor promoter. A region essential for
      transcriptional activity contains a nuclear factor binding domain.
AB  - A manifestation of Alzheimer's disease is the presence of amyloid depositions in
      brains of afflicted individuals. A major component of these depositions is the
      amyloid beta-protein, which is a truncated form of the larger amyloid beta
      protein precursor (APP). To investigate the regulation of APP gene expression,
      the APP promoter and selected deletions were placed 5' to the reporter gene
      chloramphenicol acetyltransferase. The promoter deletions were transfected into
      different cell lines that showed variant levels of endogenous APP transcripts.
      Transient transfection assays showed that 96 base pairs 5' to the transcriptional
      start site are sufficient for cell type-specific promoter activity. A nuclear
      factor that binds to this region in a sequence-specific manner was identified by
      mobility shift electrophoresis, DNase footprinting, and methylation interference.
      The DNase-protected region covers about 25 base pairs on both strands (position 
      31 to -55). Mutations within this domain revealed a sequence of 12 base pairs
      that is crucial for factor binding. This sequence overlaps with the consensus
      sequences for transcription factors AP-1 and AP-4. However, competition
      experiments suggest that the nuclear factor that binds to the APP promoter is
      distinct from both AP-1 and AP-4. Factor binding to the characterized recognition
      sequence is observed in nuclear extracts originating from human, mouse, and rat
      cells, suggesting a high degree of conservation.

PMID- 1380961
TI  - Evidence for association of the cloned liver growth hormone receptor with a
      tyrosine kinase.
AB  - The ability of the cloned liver growth hormone (GH) receptor, when expressed in
      mammalian cell lines, to copurify with tyrosine kinase activity and be tyrosyl
      phosphorylated was examined. 125I-human growth hormone-GH receptor complexes
      isolated from COS-7 cells transiently expressing high levels of the cloned liver
      GH receptor bound to anti-phosphotyrosine antibody, suggesting that the cloned GH
      receptor is tyrosyl phosphorylated in vivo. GH-GH receptor complexes purified
      from transfected COS-7 cells using anti-GH antibody incorporated 32P when
      incubated with [gamma-32P]ATP, indicating association of tyrosine kinase activity
      with cloned liver GH receptor. The level of phosphorylation of the GH receptor
      was very low, as compared with the endogenous GH receptor in 3T3-F442A cells,
      suggesting that tyrosine kinase activity is not intrinsic to the cloned GH
      receptor but rather resides with a kinase present at low levels in the COS-7
      cells. To test whether a higher level of GH receptor phosphorylation would be
      observed when the GH receptor was expressed in a different cell line, GH receptor
      cDNAs were stably transfected into mouse L and CHO cells, which have few or no
      endogenous GH receptors, and RIN5-AH cells, which do express endogenous GH
      receptors. In vivo tyrosyl phosphorylation of the cloned GH receptor in mouse L
      cells and in vitro phosphorylation of the cloned GH receptor in both L and CHO
      cells were higher than in transfected COS-7 cells but still substantially lower
      than in untransfected 3T3-F442A cells. Significantly increased 32P incorporation
      into tyrosyl residues in GH receptors in the in vitro kinase assay was
      demonstrated for GH receptors isolated from the transfected RIN5-AH cells. These
      studies show that the cloned liver GH receptor can be tyrosyl phosphorylated when
      expressed in a variety of cell types. The finding that the level of
      phosphorylation of GH receptor appears to vary with cell type is consistent with
      the cloned liver GH receptor being a substrate for an associated tyrosine kinase
      and with the amount of such a GH receptor-associated tyrosine kinase being cell
      type-specific.

PMID- 1380962
TI  - Novel amino-terminal propeptide configuration in a fibrillar procollagen
      undergoing alternative splicing.
AB  - We isolated overlapping cDNAs from embryonic libraries of the sea urchin
      Strongylocentrotus purpuratus coding for a fibrillar procollagen (2 alpha chain)
      with a predicted molecular mass of about 320 kDa. The deduced primary structure
      of the echinoid chain consists of a 265-amino acid carboxyl-propeptide, a triple
      helical domain made of 337 uninterrupted Gly-X-Y repeats, and an unusually long
      amino-propeptide. Aside from a 10-cysteine globular region, a collagenous
      sequence, and a nonhelical segment, this protein domain includes a novel 4
      cysteine motif repeated several times. Interestingly, preliminary evidence
      indicates that different combinations of the 4-cysteine repeats are encoded by
      alternatively spliced transcripts. Irrespective of this, the sea urchin 2 alpha
      procollagen chain represents the longest fibrillar molecule identified to date by
      cDNA cloning experiments in both vertebrate and invertebrate organisms.

PMID- 1380963
TI  - Nerve growth factor promotes the activation of phosphatidylinositol 3-kinase and
      its association with the trk tyrosine kinase.
AB  - We investigated the involvement of phosphatidylinositol 3-kinase (PtdIns 3
      kinase) in the initiation of signal transduction by nerve growth factor (NGF) in
      the rat pheochromocytoma PC12 cell line. PtdIns 3-kinase catalyzes the formation
      of phosphoinositides with phosphate in the D-3 position of the inositol ring and
      previously has been found to associate with other activated protein tyrosine
      kinases, including growth factor receptor tyrosine kinases. Anti-phosphotyrosine
      immunoprecipitates had PtdIns 3-kinase activity that reached a maximum (9 times
      the basal activity) after a 5-min exposure of PC12 cells to NGF (100 ng/ml).
      Since NGF activates the tyrosine kinase activity of gp140trk, the protein product
      of the trk proto-oncogene, we also examined the association of PtdIns 3-kinase
      with gp140trk. Anti-gp140trk immunoprecipitates from NGF-stimulated PC12 cells
      had increased PtdIns 3-kinase activity compared to that of unstimulated cells,
      and larger increases were detected in cells overexpressing gp140trk, indicating
      that PtdIns 3-kinase associates with gp140trk. NGF produced large increases in
      [32P]phosphatidylinositol 3,4-bisphosphate and [32P]phosphatidylinositol 3,4,5
      trisphosphate in PC12 cells labeled with [32P]orthophosphate, indicating an
      increase in PtdIns 3-kinase activity in intact cells. Using an anti-85-kDa PtdIns
      3-kinase subunit antibody, we found that NGF promoted the tyrosine
      phosphorylation of an 85-kDa protein and two proteins close to 110 kDa. These
      studies demonstrate that NGF activates PtdIns 3-kinase and promotes its
      association with gp140trk and also show that NGF promotes the tyrosine
      phosphorylation of the 85-kDa subunit of PtdIns 3-kinase. Thus, PtdIns 3-kinase
      activation appears to be involved in differentiation as well as mitogenic
      responses.

PMID- 1380964
TI  - Microvascular leakage induced by substance P in rat urinary bladder: involvement
      of cyclo-oxygenase metabolites of arachidonic acid.
AB  - 1. Intravenous administration of substance P (SP) or of the NK1 selective agonist
      [beta-Ala4, Sar9, Met (O2)11] SP-(4-11) increased vascular permeability in the
      urinary bladder of urethane-anaesthetized rats, providing evidence for an NK1
      receptor-mediated inflammatory response. 2. BW 755C, a dual inhibitor of
      arachidonate cyclo-oxygenase and lipoxygenase, significantly reduced the plasma
      extravasation induced by SP, but did not modify the effect of [beta-Ala4, Sar9,
      Met (O2)11] SP-(4-11). 3. SP-induced microvascular leakage was also inhibited by
      systemic pretreatment with indomethacin or with the prostaglandin receptor
      antagonist SC-19220, while it was unaffected by the selective 5-lipoxygenase
      inhibitor BW A4C or the leukotriene antagonist FPL 55712. 4. Pretreatment of rats
      with the mast cell degranulating agent compound 48/80 significantly attenuated
      the inflammatory effect of SP. Indomethacin administration to 48/80-pretreated
      animals failed to produce further inhibition. 5. These findings indicate that
      intravascular SP promotes plasma exudation in rat urinary bladder through an NK1
      mediated effect on venular permeability and the release of cyclo-oxygenase
      metabolites of arachidonic acid. The latter effect largely derives from the
      interaction of the neuropeptide with mast cells.

PMID- 1380966
TI  - Factors influencing survival of patients with heterotaxy syndrome undergoing the
      Fontan procedure.
AB  - OBJECTIVES: This study was undertaken to determine those factors that may
      influence survival in patients with heterotaxy syndrome undergoing the Fontan
      procedure. BACKGROUND: The Fontan procedure remains the preferred palliative
      procedure for patients with heterotaxy syndrome. Although the mortality rate has
      improved for patients without this syndrome undergoing the Fontan procedure, it
      remains high for patients with heterotaxy syndrome. METHODS: The medical records
      of 20 consecutive pediatric patients with asplenia (n = 12) and polysplenia (n =
      8) who underwent the Fontan procedure between January 1, 1986 and December 31,
      1990 were reviewed. Anatomic and hemodynamic data were collected, as well as data
      on types of surgical palliative procedures and on outcome of the Fontan
      procedure. RESULTS: There were two early and two late deaths for a total
      mortality rate of 20% in the patients with heterotaxy syndrome, as compared with
      8.5% for the patients without this syndrome who underwent the Fontan procedure
      during the same time period. Factors that significantly increased the risk of the
      Fontan procedure in these patients were 1) preoperative findings of greater than
      mild atrioventricular valve regurgitation, b) hypoplastic pulmonary arteries, and
      c) mean pulmonary artery pressure greater than or equal to 15 mm Hg after 6
      months of age. Systemic and pulmonary venous anomalies coupled with single
      ventricle anatomy were not significant risk factors for determining a poor
      outcome of the Fontan procedure. CONCLUSIONS: This study suggests that the
      outcome of the Fontan procedure in patients with heterotaxy syndrome may be
      improved by early protection of the pulmonary vascular bed, despite the existence
      of other cardiac anomalies.

PMID- 1380965
TI  - Characterization of histamine-releasing activity: role of cytokines and IgE
      heterogeneity.
AB  - Histamine-releasing factors (HRFs) are a group of cytokines that cause histamine
      release (HR) from basophils and mast cells. The concept of the priming effect of
      cytokines and the heterogeneity of IgE involved in the HRF-induced HR have been
      emphasized in recent years. In this study, we performed a series of experiments
      to elucidate the above-mentioned hypotheses. The stock HRF were obtained by
      stimulating mononuclear cells (MNC) with phytohemagglutinin (PHA). Maximal
      activity was observed 36 hr after culture. By gel filtration, HRF was eluted with
      a peak activity ranging from 12 to 18 KD. A large portion (75%) of HRF activity
      could be neutralized by a combination of antibodies against interleukin 1 (IL-1),
      IL-3, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor
      necrosis factor-alpha (TNF-alpha). The stimulation of basophils with 100 ng/ml
      each of IL-3, IL-6, IL-7, GM-CSF, or TNF-alpha alone caused 10% HR; however, when
      the cells were pretreated with 10 ng/ml of either IL-3, IL-6, IL-7, IL-8, TNF
      alpha, or GM-CSF and then stimulated with anti-IgE, a marked increase in HR was
      regularly observed. The combination of 100 ng/ml each of IL-1, IL-3, IL-8, GM
      CSF, and TNF-alpha could induce only about 20% HR; furthermore, such combinations
      did not have an additive or synergistic priming effect on anti-IgE-induced HR
      compared to the effect of single cytokines. Stripping of surface-bound IgE with
      lactic acid markedly reduced the capacity of basophils to release histamine in
      response to MNC-HRF and anti-IgE. Passive sensitization of IgE-stripped basophils
      with high-HRF responders' serum could restore their responsiveness to both MNC
      HRF and anti-IgE, but passive sensitization with low-HRF responders' serum could
      restore responsiveness to anti-IgE only. Moreover, passage of MNC-HRF through
      high-, but not low-HRF, responders' IgE-Sepharose columns significantly reduced
      the HR activity of MNC-HRF. Finally, although the eluant could induce only 10%
      HR, the majority of its HR activity could be restored by the addition of effluent
      but not by the mixture of IL-1, IL-3, IL-8, GM-CSF, and TNF-alpha, suggesting the
      presence of a complex interaction among those cytokines. In summary, MNC-HRF
      contained at least two types of HRF activity; one was IgE dependent and the other
      was IgE independent.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1380967
TI  - Tyrosine-specific protein phosphorylation in response to anti-CD3 antibody is
      diminished in old mice.
AB  - Antiphosphotyrosine immunoblots were used to characterize phosphotyrosine
      containing proteins (PY-PPNs) in anti-CD3 stimulated murine T lymphocytes.
      Activation led to increased phosphorylation of three PY-PPNs (MWs of 120, 80, and
      40 kD) within 2 minutes, and maximal phosphoprotein levels were sustained for at
      least 30 min. There was a progressive decline with age in the responses of these
      three PY-PPNs to anti-CD3 stimulation, and some 20-23-month-old mice were
      virtually nonresponsive. A second group of PY-PPNs was present in unstimulated
      cells and not affected by anti-CD3 treatment or by age. Responses to Con A and to
      an antibody to the T-cell receptor were also found to be lower in old mice. Our
      data show that the pattern of tyrosine-specific phosphorylation in normal murine
      T cells is similar but not identical to patterns previously defined in murine
      tumor T-cell lines, and that T cells in old mice have defects in tyrosine
      specific phosphorylation that could contribute to their diminished responsiveness
      to mitogenic stimuli.

PMID- 1380968
TI  - Sera and leukocyte elastase-type protease and antiprotease activity in healthy
      and atherosclerotic subjects of various ages.
AB  - Serum and granulocyte elastase-type protease activities were determined
      simultaneously with their main plasma proteinase inhibitors such as alpha-1
      antitrypsin and alpha-2-macroglobulin in healthy control and atherosclerotic
      (ATS) subjects. The age-related associations of these parameters were also
      investigated. Serum elastase-type protease activity increased, but not
      statistically significantly, with aging in both control and ATS subjects. The
      enhancement of elastase-type protease activity in sera of ATS patients was
      significantly (p less than .02) greater than control subjects only in the case of
      the elderly. The granulocytes' elastase activity was significantly greater in
      granulocytes derived from both middle-aged and elderly ATS patients (p less than
      .03 and p less than .06) compared to age-matched control subjects. Alpha-1
      antitrypsin was not significantly lower, whereas alpha-2-macroglobulin was
      significantly lower in sera of ATS subjects compared to age-matched control
      subjects (p less than .01). The conclusion is that increased elastase-type
      activity and decreased antiproteinase activity should be considered as potential
      factors in atherosclerotic arterial wall damage. The similarity of the results in
      the elderly and the ATS subjects suggest that atherosclerosis is an early aging
      process.

PMID- 1380969
TI  - [The effects of glucocorticoids on angiogenesis in vitro].
AB  - Glucocorticoids administration presumably affects the vascular system and causes
      avascular necrosis of the femoral head. However, the mechanism by which this
      occurs is still unknown. In order to clarify the action of glucocorticoids on the
      vascular system, we investigated the effects of dexamethasone on an angiogenesis
      model in vitro. The angiogenesis model was obtained by co-culturing vessel
      fragments and myofibroblastic cells from rat epididymal fat pads. In this model,
      myofibroblastic cells induce capillary formation by producing an endothelial cell
      growth factor and collagen. Dexamethasone at physiological doses inhibited
      significantly capillary growth by suppressing the collagen synthesis by
      myofibroblastic cells. However, dexamethasone had no effect on endothelial cells.
      These results indicate that glucocorticoids are related to the pathogenesis of
      avascular necrosis of the femoral head by inhibiting the repair of the vascular
      system in vivo.

PMID- 1380970
TI  - [Terminal care of final stage for digestive system diseases].

PMID- 1380971
TI  - [A case of AFP-producing lung cancer with erythrocytosis].

PMID- 1380972
TI  - Thrombin cleavage of apolipoprotein Bh of rabbit LDL: structural comparisons with
      human apolipoprotein B-100.
AB  - Rabbit plasma low density lipoprotein (LDL) contains one major apolipoprotein of
      apparent molecular weight of 320 kDa, designated apolipoprotein (apo) Bh, while
      another component termed apoB1 of apparent molecular weight of 220 kDa is found
      in chylomicrons. The fragments generated by thrombin digestion of the protein
      moieties of rabbit and human LDL were separated by polyacrylamide gradient gel
      electrophoresis and compared. As in the human species, the enzyme produced
      limited cleavage patterns of rabbit LDL apoB. Within the first 2 h, two fragments
      (Tr1 and Tr2, with apparent molecular weights 280,000 and 44,000, respectively)
      appeared. Longer incubations led to the production of two additional peptides,
      Tr3 and Tr4 (apparent molecular weights 180,000 and 96,000, respectively). Ten
      monoclonal antibodies, developed against rabbit LDL and designated P01 to P10,
      were found to react with rabbit apoB. Some also cross-reacted with human apoB.
      Epitope mapping, performed with these antibodies, showed that Tr3 and Tr4 were
      derived from the further degradation of Tr1. The rabbit is one of the most
      frequently used animals in atherosclerosis research. Its LDL receptor has been
      characterized and there exists a strain of homozygous LDL receptor-deficient
      rabbits referred to as WHHL rabbits. Despite this, little has been done to
      characterize the structure of rabbit apoB; only a short region has been sequenced
      and shown to be the carboxyl-terminal region, the rabbit apoB1. The molecular
      weight of human apoB (550,000) is much larger than rabbit apoBh. In both species,
      a primary and secondary thrombin cleavage occur, but the size of the fragments
      produced is very different between the two species. Identification of the
      thrombolytic fragments of the rabbit apoB have afforded the opportunity to
      compare the structures of both apoB species.

PMID- 1380973
TI  - Granulocyte colony-stimulating factor: a new approach in the treatment of
      childhood neutropenia.

PMID- 1380974
TI  - Disease inhibition by major histocompatibility complex binding peptide analogues
      of disease-associated epitopes: more than blocking alone.
AB  - Peptide analogues of disease-associated epitopes were studied for inhibition of
      experimental allergic encephalomyelitis (EAE) and adjuvant arthritis (AA) in
      Lewis rats. EAE- and AA-associated analogues were selected as competitors because
      of their in vitro inhibitory activity on proliferation of encephalitogenic and
      arthritogenic T cells. Although the EAE-associated competitor had a superior
      major histocompatibility complex (MHC) binding affinity, the AA-associated
      competitor was a better inhibitor of the in vitro proliferation of arthritogenic
      T cells. Furthermore, although in vivo EAE was inhibited by both competitors, AA
      was only inhibited by the AA-associated competitor. Remarkably, in contrast to
      what was expected of a regular MHC competitor peptide, the AA-associated peptide
      analogue also prevented AA upon immunization before disease induction and
      appeared to induce T cell responses that crossreacted with the original disease
      associated epitope. Therefore, it is concluded that antigen-specific regulatory
      mechanisms were involved in synergy with MHC competition. The integration of both
      qualities into a single "competitor-modulator" analogue peptide may lead to the
      development of novel, more effective, disease-specific immunomodulatory peptides.

PMID- 1380975
TI  - Septin: a factor in plasma that opsonizes lipopolysaccharide-bearing particles
      for recognition by CD14 on phagocytes.
AB  - We have previously reported that lipopolysaccharide (LPS) binding protein (LBP)
      opsonizes endotoxin (LPS) for recognition by CD14 on phagocytes. Here we show
      that normal human plasma contains high titers of an activity that also binds LPS
      (Re, 595) and mediates recognition by CD14. Opsonization of LPS-coated particles
      with plasma enables the particles to be bound by phagocytes. Further,
      opsonization with plasma also enables subnanogram-per-milliliter concentrations
      of LPS to induce dramatic alterations in the function of leukocyte integrins on
      polymorphonuclear leukocytes and to induce secretion of tumor necrosis factor by
      monocytes, suggesting that opsonization by factors in plasma may be important in
      responses of cells to endotoxin. The opsonic activity in plasma appears distinct
      from LBP since it is not blocked by neutralizing antibodies against LBP.
      Surprisingly, the opsonic activity of plasma is not present in a single protein
      species, but at least two species must be combined to observe activity. Further,
      the opsonic activity of plasma for LPS is blocked by addition of protease
      inhibitors, suggesting that proteolytic activity or activities are required for
      opsonization. These properties are suggestive of the action of a protease
      cascade, but opsonic activity of plasma is not affected by blockade or depletion
      of either the complement or clotting cascades. We propose the name "septin" to
      describe this novel LPS-opsonizing activity in plasma.

PMID- 1380976
TI  - The immunosuppressive and toxic effects of FK-506 are mechanistically related:
      pharmacology of a novel antagonist of FK-506 and rapamycin.
AB  - FK-506 inhibits Ca(2+)-dependent transcription of lymphokine genes in T cells,
      and thereby acts as a powerful immunosuppressant. However, its potential
      therapeutic applications may be seriously limited by several side effects,
      including nephrotoxicity and neurotoxicity. At present, it is unclear whether
      these immunosuppressive and toxic effects result from interference with related
      biochemical processes. FK-506 is known to interact with FK-binding protein-12
      (FKBP-12), an abundant cytosolic protein with cis-trans peptidyl-prolyl isomerase
      activity (PPIase) activity. Because rapamycin (RAP) similarly binds to FKBP-12,
      although it acts in a manner different from FK-506, by inhibiting T cell
      responses to lymphokines, such an interaction with FKBP-12 is not sufficient to
      mediate immunosuppression. Recently, it was found that the complex of FKBP-12
      with FK-506, but not with RAP, inhibits the phosphatase activity of calcineurin.
      Here, we used L-685,818, the C18-hydroxy, C21-ethyl derivative of FK-506, to
      explore further the role of FKBP-12 in the immunosuppressive and toxic actions of
      FK-506. Although L-685,818 bound with high affinity to FKBP-12 and inhibited its
      PPIase activity, it did not suppress T cell activation, and, when complexed with
      FKBP-12, did not affect calcineurin phosphatase activity. However, L-685,818 was
      a potent antagonist of the immunosuppressive activity of both FK-506 and RAP.
      Moreover, L-685,818 did not induce any toxicity in dogs and rats or in a mouse
      model of acute FK-506 nephrotoxicity, but it blocked the effect of FK-506 in this
      model. Therefore, FK-506 toxicity involves the disruption of biochemical
      mechanisms related to those implicated in T cell activation. Like
      immunosuppression, this toxicity is not due to the inhibition of the PPIase
      activity of FKBP-12, but may be linked to the inhibition of the phosphatase
      activity of calcineurin by the drug FKBP-12 complex.

PMID- 1380977
TI  - The CD45 tyrosine phosphatase regulates phosphotyrosine homeostasis and its loss
      reveals a novel pattern of late T cell receptor-induced Ca2+ oscillations.
AB  - CD45 is a transmembrane tyrosine phosphatase implicated in T cell antigen
      receptor (TCR)-mediated activation. In T cell variants expressing progressively
      lower levels of CD45 (from normal to undetectable), CD45 expression was inversely
      related to spontaneous tyrosine phosphorylation of multiple proteins, including
      the TCR zeta chain, and was directly correlated with TCR-driven phosphoinositide
      hydrolysis. The Ca2+ response in these cells was altered in an unexpected
      fashion. Unlike wild-type cells, stimulated CD45- cell populations did not
      manifest an early increase in intracellular Ca2+, but did exhibit a delayed and
      gradual increase in mean intracellular Ca2+. Computer-aided fluorescence imaging
      of individual cells revealed that CD45- cells experienced late Ca2+ oscillations
      that were not blocked by removal of extracellular Ca2+. CD45 revertants had the
      signaling properties of wild-type cells. Thus, CD45 has a profound influence on
      both TCR-mediated signaling and phosphotyrosine homeostasis, and its loss reveals
      a novel role for this tyrosine phosphatase in Ca2+ regulation.

PMID- 1380978
TI  - Activation of nonselective cation channels by physiological cholecystokinin
      concentrations in mouse pancreatic acinar cells.
AB  - The activation of the nonselective cation channels in mouse pancreatic acinar
      cells has been assessed at low agonist concentrations using patch-clamp whole
      cell, cell-attached patch, and isolated inside-out patch recordings. Application
      of acetylcholine (ACh) (25-1,000 nM) and cholecystokinin (CCK) (2-10 pM) evoked
      oscillatory responses in both cation and chloride currents measured in whole cell
      experiments. In cell-attached patch experiments we demonstrate CCK and ACh evoked
      opening of single 25-pS cation channels in the basolateral membrane. Therefore,
      at least a component of the whole cell cation current is due to activation of
      cation channels in the basolateral acinar cell membrane. To further investigate
      the reported sensitivity of the cation channel to intracellular ATP and calcium
      we used excised inside-out patches. Micromolar Ca2+ concentrations were required
      for significant channel activation. Application of ATP and ADP to the
      intracellular surface of the patch blocked channel opening at concentrations
      between 0.2 and 4 mM. The nonmetabolizable ATP analogue, 5'
      adenylylimidodiphosphate (AMP-PNP, 0.2-2 mM), also effectively blocked channel
      opening. The subsequent removal of ATP caused a transient increase in channel
      activity not seen with the removal of ADP or AMP-PNP. Patches isolated into
      solutions containing 2 mM ATP showed channel activation at micromolar Ca2+
      concentrations. Our results show that ATP has two separate effects. The
      continuous presence of the nucleotide is required for operation of the cation
      channels and this action seems to depend on ATP hydrolysis. ATP can also close
      the channel and this effect can be demonstrated in excised inside-out patches
      when ATP is added to the bath after a period of exposure to an ATP-free solution.
      This action does not require ATP hydrolysis. Under physiological conditions
      hormonal stimulation can open the nonselective cation channels and this can be
      explained by the rise in the intracellular free Ca2+ concentration.

PMID- 1380979
TI  - Demonstration of peptidoglycan-associated Brucella outer-membrane proteins by use
      of monoclonal antibodies.
AB  - A monoclonal antibody (3D6) was produced which reacted only with Brucella
      sonicated cell extracts that had been lysozyme-treated after sonication. The
      monoclonal antibody (mAb) reacted with the three major outer-membrane proteins
      (OMPs) of B. melitensis B115 in Western blots. A large number of reactive bands
      ranging from 12 to 43 kDa were present in lysozyme-treated Escherichia coli and
      Yersinia enterocolitica sonicated cell extracts. In a latex agglutination
      inhibition immunoassay, mAb 3D6 showed better reactivity with purified
      peptidoglycan (PG) of B. melitensis B115 than with that of Escherichia coli. This
      mAb was also used in immunogold electron microscopy with whole Brucella cells and
      sections. No binding was observed on whole cells and immunogold labelling in
      sections was observed close to the outer membrane, in the periplasmic space and
      in the cytoplasm. These findings indicate that mAb 3D6 is specific for PG
      subunits. Immunoblot analysis of B. melitensis B115 rough sonicated cell extracts
      after SDS-PAGE, with or without lysozyme treatment, was performed using mAbs
      specific for Brucella OMPs of molecular masses of 10, 16.5, 19, 25-27, 31-34, 36
      38 and 89 kDa, for PG and for rough lipopolysaccharide (R-LPS) and smooth
      lipopolysaccharide (S-LPS). mAbs specific for the 25-27, 31-34 and 36-38 kDa OMPs
      reacted with three to six bands. All of them except the band of lowest molecular
      mass reacted with the PG-specific mAb and not with R-LPS- and S-LPS-specific
      mAbs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380980
TI  - Pharmacological models of generalized absence seizures in rodents.
AB  - A number of animal models of generalized absence seizures in rodents are
      described. These include absence seizures induced by gamma-hydroxybutyrate (GHB),
      low dose pentylenetetrazole, penicillin, THIP, and AY-9944. All of these models
      share behavioral and EEG similarity to human absence seizures and show
      pharmacologic specificity for antiabsence drugs such as ethosuximide and
      trimethadione. Moreover, the absence seizures induced by these agents are
      exacerbated by GABAergic agonists, a property unique to experimental absence
      seizures. These models are predictable, reproducible, and easy to standardize.
      They are useful both in studying mechanisms of pathogenesis of absence seizures
      as well as in screening for antiabsence activity of potential antiepileptic
      drugs.

PMID- 1380981
TI  - Argentophilic intracytoplasmic inclusions in multiple system atrophy.
AB  - Argentophilic intracytoplasmic glial inclusions were recently reported in olivo
      ponto-cerebellar atrophy (OPCA). We examined the brains of 3 cases of OPCA [2
      with striato-nigral degeneration (SND) and 1 without SND], 1 case of pure
      autonomic failure (PAF) without pathology of OPCA or SND, as well as 36 controls
      including 2 cases of Holmes' type cerebellar cortical atrophy and 2 cases of
      Joseph's disease. Although the inclusions were tubulin-positive, the
      immunoreactivity was different from that of the dendrites. Electron
      microscopically, the microtubular structures composing the inclusion were fuzzy
      with granular material. These findings may indicate that the microtubules
      composing the inclusions are modified. Inclusion-bearing cells appeared to be
      oligodendrocytes while many of them had larger and lighter nuclei than those of
      normal-looking oligodendrocytes without the inclusions. The inclusions were
      widely distributed in a characteristic fashion beyond the typical lesions of
      OPCA, SND and PAF. The distribution pattern was essentially the same in the case
      of PAF and 3 cases of OPCA irrespective of the presence or absence of OPCA or SND
      lesions. In contrast, argentophilic inclusions were not observed in other types
      of spinocerebellar degeneration, in Holmes' type cerebellar cortical atrophy or
      in Joseph's disease. It is suggested, in line with other studies, that the
      inclusion may be specific to OPCA and related disorders which include PAF and a
      useful marker to distinguish OPCA from other neurodegenerative diseases.

PMID- 1380982
TI  - Growth charts only marginally improved maternal learning from nutrition education
      and growth monitoring in Lesotho.
AB  - A study done in Lesotho in 1985-1986 assessed whether growth charts increased the
      impact of nutrition education and growth monitoring on maternal learning about
      weaning practices and diarrhea. Seven hundred and seventy six mothers were given
      three monthly sessions of group nutrition education along with growth monitoring
      of children and individual counseling. Growth charts, which were taught to one of
      two groups, fostered learning but only on issues related to diarrhea and only
      among new clinic attendants, mothers with less than secondary schooling and
      mothers of malnourished children. These benefits, however, were small
      (differences less than 10%) compared with the overall impact of the nutrition
      education and growth monitoring intervention (increases between baseline and post
      intervention were greater than 50% for some questions). Our findings suggest that
      well-designed clinic-based nutrition education and growth monitoring can have a
      significant impact on maternal nutrition knowledge. Teaching growth charts to
      mothers may not be necessary for obtaining such results in programs conducted
      under ideal conditions. More research is needed to determine under what
      circumstances, for what purposes and for whom growth charts may be beneficial.

PMID- 1380983
TI  - Carbohydrate intake determines pancreatic acinar amylase activity and release
      despite chronic alcoholemia in rats.
AB  - Adverse effects observed in alcoholic rats are often attributed to alcohol per
      se. Alcoholic liver damage, however, can be avoided by modulating nutritional
      factors despite high blood alcohol concentrations. Hence, we examined the effect
      of blood alcohol concentration on pancreatic enzyme activity and release. Three
      liquid diets containing 36 and 18% of total energy derived from alcohol and
      protein, respectively, were fed. Each alcohol diet contained 11, 21 or 31% of
      energy from carbohydrate, and the fat concentration was appropriately adjusted.
      The control groups of rats (fed an isoenergetic liquid diet without alcohol) and
      the alcoholic groups of rats were maintained for 2 wk. The three groups of
      alcoholic rats consumed 13.3 +/- 2.3, 13.3 +/- 2.2 and 13.2 +/- 1.9 g/kg of
      alcohol daily, and their corresponding blood alcohol levels were 41.5 +/- 4.3,
      55.4 +/- 8.9 and 44.6 +/- 2.2 mmol/L. Pancreatic acinar amylase activity in
      alcoholic rats was proportional to carbohydrate ingested, despite high blood
      alcohol concentrations; chymotrypsin and trypsin activities were unchanged.
      Acinar enzyme activities in control rats were similar. Furthermore,
      cholecystokinin-octapeptide-stimulated amylase release in alcoholic rats
      corresponded with the amylase concentration in acini, whereas stimulated trypsin
      output was unaltered in both control and alcoholic rats. These results
      demonstrate that neither alcohol ingestion nor high blood alcohol concentration
      affects the activities of pancreatic proteases and that the changes in the
      activity and release of amylase are related to the intake of carbohydrate.

PMID- 1380984
TI  - [Studies on the function of mast cells infiltrating in nasal polyps].
AB  - The function of nasal polyp mast cells has not been elucidated despite the large
      number of these cells observed in tissues. We examined these mast cells
      histochemically, immunohistologically and functionally. Ninety-three percent of
      collagenase dispersed cells in a nasal polyp were formalin-sensitive. These
      dispersed cells released histamine in reaction to calcium ionophore A23187 in a
      dose dependent manner, but not in response to C5a, Compound 48/80 or Substance P.
      From these results, dispersed mast cells from nasal polyps were considered to be
      analogous to dispersed mast cells from the human lung and nasal mucosa but not
      those from human skin. On the other hand, in the reaction with anti-human IgE,
      dispersed mast cells from a non allergic nasal polyp could not be seen to release
      histamine. In only 2 of 7 patients, could histamine release in response to
      Japanese red cedar antigen, from mast cells sensitized passively with the serum
      of Japanese red cedar pollinosis, seen. Using small tissue samples from polyps,
      histamine was released by anti-human IgE in allergic patients but not in non
      allergic patients. Immunohistologically in allergic nasal polyps, some IgE
      positive mast cells could be seen, whereas in non allergic polyps these cells
      were absent. These observations suggest that mast cells which had accumulated in
      nasal polyps both with and without allergy were capable of functional histamine
      release, whereas in the nasal polyps of allergy patients but not in non-allergic
      patients these cells are involved in IgE mediated reactions.

PMID- 1380985
TI  - [Inhibitory activity of mite IgG4, antibody on antigen-induced histamine release
      from human peripheral blood leukocytes].
AB  - Several reports have yielded conflicting results on the role of IgG4 antibody on
      the surfaces of target cells in immediate type allergy. This study was performed
      to elucidate whether IgG4 antibody inhibits IgE-mediated histamine release from
      target cells after antigenic stimulation, and whether it has reaginic activity.
      Serum was obtained from patients with nasal allergy receiving specific
      immunotherapy for housedust and mites. IgE and IgG4 were enriched affinity
      chromatographically using monoclonal antibodies to IgE and IgG4, respectively,
      from the pooled sera. Both fraction revealed high antibody activity to
      Dermatophagoides Farinae antigen. Peripheral blood leukocytes from three non
      allergic donors were passively sensitized with 100 or 300 micrograms of IgG4
      according to the method of Levy and Osler with a slight modification. Minimal or
      no histamine release was observed from leukocytes after challenge with both mite
      antigen and anti-IgG4 monoclonal antibodies. Furthermore, to investigate the
      reaginic activity of IgG4, leukocytes from patients with nasal allergy were
      stimulated with anti-IgG4 antibodies. The leukocytes of only three out of twenty
      patients released up to 10% histamine regardless of the IgG4 concentration, while
      the other patients' leukocytes released minimal amounts of histamine. Two of the
      three above-mentioned non-allergic donors were passively sensitized with 100 or
      300 micrograms of IgG4 either one hour after sensitization with 100 ngs of IgE or
      simultaneously with the same amount of IgE. After sensitization with 100 ngs of
      IgE, one showed high-grade histamine release after challenge with 0.5
      micrograms/ml mite antigen and the other showed middle-grade release with 0.1
      micrograms/ml mite. With the presence of 300 micrograms of IgG4, histamine
      release was significantly inhibited in both donors regardless of the manner of
      sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1380986
TI  - Endodermal sinus tumor of vulva (a case report).
AB  - An unusual case of endodermal sinus tumor (EST) of the ovary at an extragonadal
      site-vulva, in an unmarried female of 25 yr is reported. The patient presented
      only with a vulval swelling on the right side without any other signs or
      symptoms. The internal genital organs mainly the ovaries were normal.

PMID- 1380987
TI  - Activation and differentiation of myelomonocytic cells in rheumatoid arthritis
      and healthy individuals--evidence for antagonistic in vitro regulation by
      interferon-gamma and tumor necrosis factor alpha, granulocyte monocyte colony
      stimulating factor and interleukin 1.
AB  - We analyzed expression of HLA-DR and CD14 molecules on myelomonocytic cells and
      its regulation by various inflammatory cytokines in 6 patients with rheumatoid
      arthritis (RA) and 4 healthy individuals who had undergone bone marrow
      aspiration. At start of the bone marrow culture there was a significantly higher
      number of HLA-DR and CD14 positive bone marrow mononuclear cells in patients with
      RA than in normals. In addition, RA bone marrow mononuclear cells expressed an up
      to 10-fold higher mean density of both molecules than normal bone marrow
      mononuclear cells during the whole culture period of up to 14 days. The effect of
      the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF
      alpha), granulocyte monocyte colony stimulating factor (GM-CSF) and interleukin 1
      (IL-1) on the expression of CD14 or HLA-DR was different: IFN-gamma strongly
      upregulated HLA-DR expression and down-regulated CD14 expression while TNF alpha,
      GM-CSF and IL-1 mainly stimulated CD14 expression on bone marrow mononuclear
      cells. Our data suggest that RA bone marrow mononuclear cells exhibit an
      activated phenotype and that TNF-alpha GM-CSF and IL-1 mainly stimulate the
      differentiation of bone marrow macrophages whereas IFN-gamma activates them.

PMID- 1380988
TI  - Analysis of lymphocyte phenotype and T cell receptor genotype in Felty's
      syndrome.
AB  - Natural killer (NK) cells and CD3+ large granular lymphocytes (LGL) were
      investigated in patients with Felty's syndrome (FS), rheumatoid arthritis (RA)
      and healthy controls. In most patients with FS, NK cell number and activity were
      decreased. CD3+ LGL were unchanged. However, in one patient a marked expansion of
      CD3- CD16+ CD56+ (NK) cells was seen and in a second, an expansion of CD3+ LGL.
      In FS there was also an increase in HLA- DR+ and CD8+ but not gamma delta+ T
      cells. Three of 11 patients with FS studied demonstrated a dominant rearrangement
      of the T cell receptor beta gene constant region consistent with oligoclonal T
      cell expansion.

PMID- 1380990
TI  - Influence of testicular carcinoma on ipsilateral spermatogenesis.
AB  - A histological review of radical orchiectomy specimens was performed to assess
      the impact of testicular cancer on spermatogenesis. Slides from 28 patients with
      testicular cancer were available for review, consisting of 14 pure seminomas, 12
      embryonal carcinomas and 2 mixed tumors. For each specimen tubules adjacent (less
      than 3 mm.) to the tumor and distant (more than 3 mm.) from the tumor were
      evaluated. This study indicates that marked impairment of ipsilateral
      spermatogenesis is associated with testicular carcinoma, particularly in the
      vicinity of the tumor. The quality of distant spermatogenesis appears to be
      influenced by tumor type and not by elevation of known serum tumor markers, such
      as human chorionic gonadotropin and alpha-fetoprotein, nor by the presence of
      carcinoma in situ.

PMID- 1380989
TI  - Treatment of recurrent gliomas with eflornithine.
AB  - BACKGROUND: Oral eflornithine in combination with intravenous mitoguazone
      (methylbisguanylhydrazone) has shown activity against recurrent anaplastic
      gliomas. Eflornithine alone, however, has not been evaluated against recurrent
      gliomas. PURPOSE: This study compared the antitumor activity of oral eflornithine
      with that of oral eflornithine combined with intravenous mitoguazone in the
      treatment of patients with recurrent or progressive glioblastoma multiforme as
      well as nonglioblastoma anaplastic gliomas. METHODS: During the 1st year of
      therapy with eflornithine alone, the drug was given at a dose of 3.6 g/m2 on days
      1-14, 22-35, and 43-56 every 8 hours; cycles were repeated every 63 days until
      progression. For the 2nd year, the drug was given on days 1-14, 29-42, and 57-70,
      with 84 days between cycles. For the 1st and 2nd years of eflornithine
      mitoguazone therapy, eflornithine was given at 1.8 g/m2 on the same schedule.
      Mitoguazone was given intravenously at 200 mg/m2 on the final day of each 2-week
      sequence of eflornithine therapy. Response was determined by evaluating changes
      in the size of contrast-enhanced neuroimages. RESULTS: Because of two cases of
      lethal hepatic necrosis, the initial random allocation of patients to the
      eflornithine-mitoguazone arm was stopped after 23 patients had been accrued.
      Ninety-eight patients were entered in the eflornithine arm; 80 patients (36
      glioblastoma multiforme patients and 44 anaplastic glioma patients) were
      assessable for response. Antitumor activity (partial response, minor response,
      and stable disease) was seen in 45% of the patients with anaplastic gliomas, for
      a median of 49 weeks, but in only 17% of patients with glioblastoma multiforme
      (median not attained). Twenty-one (20%) of the patients with anaplastic glioma
      and 33% of the patients with glioblastoma multiforme were removed from the study
      before completing the first 8-week course of therapy because of neurological
      deterioration and tumor progression by the 5th week of treatment. CONCLUSION:
      This study suggests that eflornithine alone is an effective palliative therapy
      for recurrent anaplastic gliomas. Additional studies are needed to confirm our
      finding.

PMID- 1380991
TI  - Detection of clinically significant prostate cancer by transrectal ultrasound
      guided systematic biopsies.
AB  - Systematic biopsies are a useful, sensitive means to detect carcinoma of the
      prostate. However, multiple biopsies pose a risk for detecting clinically
      insignificant prostate cancer, that is those cancers less than 0.5 cc in volume,
      which occur in approximately 32% of all white men more than 50 years old.
      Systematic biopsies were positive for cancer in 442 of 816 patients and 60 (14%)
      demonstrated only a minute focus of cancer (3 mm. or less) in 1 of the 6 biopsy
      specimens. In 27 patients with these minute foci who underwent radical
      prostatectomy a wide range of cancer volumes was observed; 30% of these 27
      cancers were less than 0.5 cc (15% less than 0.2 cc) and may not have required
      therapy. Thus, the overall risk of detecting an insignificant cancer is 4.0% with
      systematic biopsies. Performance of confirmatory biopsies in patients with a
      minute focus (3 mm. or less) of cancer on initial systematic biopsies resulted in
      cancers less than 0.5 cc being removed in only 1 of 10 radical prostatectomies
      (10%, none was less than 0.2 cc). Thus, with the addition of confirmatory
      biopsies the risk of detecting insignificant cancer is 1.4%. Conservative
      management is recommended for patients without significant cancer on repeat
      biopsies in whom initial biopsies have revealed only a minute focus of cancer in
      1 of the biopsy cores. We believe that concern is also warranted for patients who
      have 3 mm. or less of cancer demonstrated by several nonsystematic biopsies
      directed at a suspicious hypoechoic lesion in whom the digital rectal examination
      is normal.

PMID- 1380992
TI  - Quantitative estimation of tissue prostate specific antigen, deoxyribonucleic
      acid ploidy and cytological grade in fine needle aspiration biopsies for
      prognosis of hormonally treated prostatic carcinoma.
AB  - The prognostic value of deoxyribonucleic acid (DNA) flow cytometry, cytological
      grading and the direct assay of prostate specific antigen (PSA) in the material
      of fine needle aspirates was studied in 67 consecutive patients with newly
      detected prostatic carcinoma. All patients were hormonally treated (castration in
      27 and luteinizing hormone-releasing hormone agonist or parenteral estrogens in
      40). The patients were followed for a minimum of 2 years. PSA was analyzed in the
      biopsy material by a direct radioimmunoassay and related to the total amount of
      DNA. In parallel biopsies DNA ploidy using flow cytometry and cytological grade
      were established. Patients with a geometric mean value of greater than or equal
      to 0.12 microgram. PSA/microgram. DNA had a progression rate of 7%, compared to
      59% for those with less than 0.12 microgram. PSA/microgram. DNA. In Cox
      multivariate analysis cytology and tissue PSA content were the most important
      factors in expressing the difference for interval to progression in hormonally
      treated patients.

PMID- 1380993
TI  - Comparative response of nestling European starlings and red-winged blackbirds to
      an oral administration of either dimethoate or chlorpyrifos.
AB  - Red-winged blackbird (Agelaius phoeniceus; blackbird) and European starling
      (Sturnus vulgaris; starling) nestlings were dosed with either 2.0 mg/kg body mass
      chlorpyrifos, 50.0 mg/kg body mass dimethoate, or a propylene glycol carrier in
      situ. Four growth measurements (body mass, culmen, tarsus, wing) were recorded
      from nestlings to determine if these organophosphorus compounds caused
      perturbations in development at sublethal concentrations. Blackbird nestlings
      were more sensitive to chlorpyrifos than starling nestlings were more sensitive
      to dimethoate than blackbird nestlings. This was in contrast to reported adult
      LD50 values where the reverse was true. Blackbird nestlings were more tolerant of
      a substantially higher concentration of dimethoate than the adult LD50. The
      sensitivity of starling nestlings to dimethoate was similar to adults. In
      contrast, juveniles of both species were more sensitive to chlorpyrifos than
      adults. After the initial 24 hr, surviving nestlings dosed with either chemical
      recovered and continued their development. Exposure to dimethoate caused
      significant depression in starling body mass during the initial 24 hr period.
      Survivors obtain body mass equal to controls within 48 hr post dosing. The
      research presented here demonstrates that the simple supposition that passerine
      nestlings are typically more sensitive to toxins than adults does not always hold
      true. It also indicates that sensitivity relationships among adults do not
      necessarily apply to their nestlings.

PMID- 1380995
TI  - From the Food and Drug Administration.

PMID- 1380994
TI  - Keratitis in free-ranging koalas (Phascolarctos cinereus) on Magnetic Island,
      Townsville.
AB  - Seventy free-ranging koalas (Phascolarctos cinereus) from Magnetic Island
      (Queensland, Australia) underwent an ocular examination, blood collection and
      serological examination for Chlamydia psittaci antibodies, and an examination of
      their teeth and genitalia. In 12 koalas long-standing unilateral keratitis was
      noted and in another 10 animals long-standing bilateral keratitis was observed.
      All animals were seronegative for Chlamydia psittaci and apart from some nasal
      discharge and a variety of assorted medical findings there was no sign of
      chlamydial infection. These ocular findings probably represent a new disease of
      unknown etiology.

PMID- 1380996
TI  - [Effects of oxygen free radicals on cell growth and productions of alpha
      fetoprotein (AFP) and albumin (ALB) by human hepatoma cell line (HH2-6)].
AB  - Secreting and producing capacities of alpha-fetoprotein (AFP) and albumin (ALB)
      by human hepatoma cell line (HH2-6) exposed to oxygen free radicals generated by
      dihydroxyfumarate (DHF) were studied in vitro. It was found that cell number were
      declined in proportion to DHF concentrations for 48 hrs culture and cell
      proliferations were inhibited by DHF in growth curve. The amount of AFP secreted
      per cell (secreting capacity) was decreased at high concentration of DHF (50
      micrograms/ml) for 48 hrs culture, and remarkable elevation of AFP-secreting
      capacity for growth stage was inhibited even by DHF (10 micrograms/ml). On the
      other hand, ALB-secreting capacity was not affected with DHF. Producing
      capacities of AFP and ALB were correlated with secreting capacities. Cu, Zn
      superoxide dismutase (Cu, Zn-SOD) interfered these reactions. These results
      suggest that oxygen free radicals inhibit cell proliferations and suppress AFP
      secreting and producing capacities of HH2-6 cells selectively.

PMID- 1380997
TI  - [Molecular size heterogeneity of SPan-1 antigen and co-expression with Lewis
      phenotype determinants in sera from gastrointestinal malignant diseases].
AB  - Molecular size of SPan-1 antigen and co-expression between SPan-1 epitope and
      Lewis phenotype determinants (LPD) on the same molecule in sera from patients
      with pancreatic, gastric and colon cancer and in culture medium from cancer cell
      line were studied. Column chromatography study on culture medium and sera showed
      that SPan-1 immunoreactivity was found in the void volume region as single major
      peak, or followed by one or two minor peak in the included volume. All of 4
      pancreatic cancer cell lines showed molecular size heterogeneity. Co-expression
      between SPan-1 epitope and LPD on the same molecule was recognized in sera from
      cancer patients with Lewis a or Lewis b positive, but not in patients with Lewis
      a-, b-. Molecular carrying SPan-1 epitope had more frequently SPan-1 epitope than
      LPD in sera from cancer patients. These findings suggest that molecular size
      heterogeneity of SPan-1 antigen was more often in pancreatic cancer cells and
      overexpression of SPan-1 epitope on the same molecule seems to be specific for
      cancer.

PMID- 1380998
TI  - [Effects of nutritional status on contents of tryptophan, serotonin and 5
      hydroxyindoleacetic acid in rat brain].
AB  - Effects of nutritional status on the levels of tryptophan (Trp), serotonin (5HT),
      and its metabolite, 5-hydroxyindoleacetic acid (5HIAA) in six brain regions of
      rats were investigated. 1) A low-protein high-carbohydrate diet decreased Trp,
      5HT and 5HIAA levels in the cortex and hippocampus, and those of 5HT and 5HIAA in
      the hypothalamus. This diet did not affect the contents of Trp and 5HT in the
      midbrain, but decreased 5HIAA. No significant changes of Trp, 5HT and 5HIAA were
      observed in the pons and medulla and striatum. 2) A low-carbohydrate high-protein
      diet increased the levels of Trp, 5HT and 5HIAA in the striatum, and 5HT and
      5HIAA in the cortex, but showed no effect on the contents of Trp, 5HT and 5HIAA
      in the hippocampus, midbrain, pons and medulla and hypothalamus. 3) An energy
      restriction low-carbohydrate diet increased Trp, 5HT and 5HIAA contents in the
      striatum, and 5HT and 5HIAA in the cortex and pons and medulla. In the
      hypothalamus, only 5HIAA was increased by this diet. The diet did not influence
      Trp, 5HT and 5HIAA contents of the midbrain and hippocampus. These results
      suggest that i) lowered fat and carbohydrate intakes enhance 5HT synthesis and
      metabolism in the cortex and that lowered carbohydrate intake enhances them in
      the striatum, ii) energy restriction enhances the 5HT metabolism in the cortex,
      pons and medulla and hypothalamus, and 5HT synthesis in the cortex and pons and
      medulla, iii) lowered protein intake inhibits 5HT metabolism in the cortex,
      midbrain, hippocampus and hypothalamus, and 5HT synthesis in the cortex,
      hippocampus and hypothalamus.

PMID- 1380999
TI  - Sites of action of 2-thiazoline-2-thiol on biogenesis of thyroid hormones.
AB  - 2-Thiazoline-2-thiol is an antithyroid agent that strongly reduces thyroid
      hormone levels. Synthesis of these hormones is catalyzed in vivo by thyroid
      peroxidase. The interaction of this drug with molecular iodine and its effect on
      peroxidase activity were investigated. Iodine and 2-thiazoline-2-thiol form a
      complex of the charge transfer type of 1:1 stoichiometry characterized by a
      formation constant of 2,527 l.mole-1 at 20 degrees C. This drug was found to
      inhibit both horseradish peroxidase and lactoperoxidase (used as a model of
      thyroid peroxidase) in a competitive manner, giving inhibition constants of 5.7
      mM and 0.13 mM, respectively. T3 and T4 levels were reduced significantly after a
      three-week administration of this drug to a group of 10 rats. Histological
      examination of the thyroid gland showed the presence of a cylindrical epithelium,
      which is indicative of hyperactivity of the gland. The results indicated that 2
      thiazoline-2-thiol acts on both molecular iodine and thyroid peroxidase.

PMID- 1381000
TI  - Effects of inhibitors of protein kinase C on the release and synthesis of
      histamine in rat basophilic leukemia cells (2H3).
AB  - In rat basophilic leukemia cells (2H3), a tumor analog of mast cells, the
      aggregation of IgE receptors results in histamine secretion and the increase in
      histidine decarboxylase activity which synthesizes histamine. Using inhibitors of
      protein kinases C, we studied the relationships between these events and protein
      kinase C which is activated by antigens. Histamine release is suppressed by
      inhibitors of protein kinase C, staurosporine, K252-a and H-7, in this decreasing
      order of effectiveness; and the IC50 values are 1.5 nM, 29.9 nM and 3.8 microM,
      respectively. The changes in the intracellular Ca concentration monitored by fura
      2 fluorescence is not modified by staurosporine, although the histamine response
      is suppressed. Meanwhile, the increase of histidine decarboxylase was abolished
      by inhibitors of protein kinase C; staurosporine was the strongest, K-252a of
      moderate activity and H-7, the weakest, having IC50 values of 0.8 nM, 100 nM and
      11.5 microM, respectively. The inhibitors of protein kinase C suppress both
      histamine secretion and synthesis. Therefore, the histamine synthesis may be
      stimulated via activation of protein kinase C to supplement the released
      histamine.

PMID- 1381001
TI  - Sialogogic effects on rat submandibular gland of analogs of the C-terminal
      hexapeptide of substance P.
AB  - The sialogogic response of submandibular glands to analogs of the C-terminal
      hexapeptide of substance P with various amino acids at the N-terminus was
      investigated in urethane-anesthetized rats. The rank order of potencies was as
      follows: SP greater than (pGlu6)SP6-11 much greater than (Dab6)SP6-11 greater
      than (Orn6)SP6-11 greater than (Gln6)SP6-11 greater than (Lys6)SP6-11 much
      greater than (Ala6)SP6-11. These results suggest that the sialogogic activity of
      the analogs of the C-terminal hexapeptide is influenced by the steric effects of
      the N-terminal amino acid, and the nature of its side chain is of particular
      importance.

PMID- 1381002
TI  - Risk factors for dialysis-associated hepatitis C in Venezuela.
AB  - Utilizing the first and second generation of enzyme immunoassays which detect
      antibodies to the C virus we investigated the frequency of anti-HCV antibodies in
      315 patients undergoing hemodialysis. Other subpopulations at risk were used as
      reference groups. One hundred and twenty-three samples (39%) from the
      hemodialysis group repeatedly showed anti-HCV positive antibodies while only 19%
      and 1% were positive in the reference groups. The rate of anti-HCV reactive
      patients correlated with time on hemodialysis (less than 1 year, 17%; 1 to 5
      years 43%; greater than 5 years, 64%; r = 0.94, P less than 0.001) and with the
      number of blood transfusions (1 to 10, 40%; greater than 10, 76%; r = 0.97; P
      less than 0.001). Length of time on hemodialysis was shown to be the major risk
      factor in thirty-three anti-HCV positive patients who had no previous record of
      blood transfusions. Co-infection with HBV was demonstrated in 41% out of 123 anti
      HCV reactive patients, and increased alanine aminotransferase (ALT) activity was
      documented in this co-infected group. Our results further extend the observations
      on the predisposing factors to HCV spread in hemodialysis units, and suggest that
      in these renal patients co-infection with C and B viruses is a major cause of
      rising ALT activity.

PMID- 1381003
TI  - HLA class II specificities in vasculitis with antibodies to neutrophil
      cytoplasmic antigens.
AB  - HLA class II genes were examined in patients with small vessel vasculitis
      associated with anti-neutrophil cytoplasmic antibodies (ANCA) using restriction
      fragment length polymorphism and allele specific oligonucleotide typing. Fifty
      nine patients were studied, 34 with Wegener's granulomatosis and 25 with
      microscopic polyarteritis, and their results were compared with those from 1103
      British Caucasoid controls. The frequency of HLA-DQw7 was significantly increased
      in patients with vasculitis (patients 53%; controls 27.8%, chi 2 17.8, Pc less
      than 0.0025, relative risk 2.9), and all the DQw7 bearing haplotypes commonly
      found in Caucasoid populations contributed to the increase. By contrast, the
      frequency of HLA-DR3 bearing haplotypes was decreased in the patients (patients
      6.8%; controls 21.6%, chi 2 6.7, P less than 0.01). HLA specificities were
      similar in the groups of patients presenting with Wegener's granulomatosis and
      microscopic polyarteritis and with different types of ANCA assessed by indirect
      immunofluorescence. However, patients with the DQw7, DR4 haplotype were
      significantly more likely to have transiently positive tests for ANCA than
      patients with other DQw7 bearing haplotypes, whereas patients with DR2 bearing
      haplotypes were more likely to have persistently positive ANCA. These results
      show that HLA class II genes are associated with small vessel vasculitis and may
      influence the duration of the associated autoimmune response.

PMID- 1381004
TI  - Early increased renal procollagen alpha 1(IV) mRNA levels in streptozotocin
      induced diabetes.
AB  - Changes in renal procollagen mRNA levels were measured shortly after the
      induction of streptozotocin induced diabetes in the rat. "Medullary" procollagen
      alpha 1(IV) levels seven days after diabetes induction was significantly higher
      in untreated diabetic rats (DM, N = 12; 244 +/- 57% of the mean control value),
      than in diabetic rats receiving small doses of insulin insufficient to achieve
      euglycemia (NPH, N = 10; 87 +/- 12%) and in diluent injected nondiabetic control
      rats (C, N = 15; 100 +/- 12%; P less than 0.01, DM vs. C and DM vs. NPH).
      "Medullary" procollagen alpha 1(I) mRNA levels were numerically increased in DM
      to a lesser degree (141 +/- 5%, ANOVA not significant) compared to C (100 +/-
      13%), and this small increment was further normalized by insulin treatment (NPH,
      120 +/- 11%). A trend for increased beta-actin mRNA levels in DM did not reach
      significance (P greater than 0.05). Increases in "medullary" procollagen mRNA
      levels did not correlate with kidney weight, glomerular tuft volume, creatinine
      clearance, food intake, or body weight gain, and occurred when renal morphology
      was normal by light microscopy. Statistically significant but weak correlations
      were noted between the serum glucose levels and "medullary" procollagen alpha
      1(IV) mRNA levels (r = 0.43, P less than 0.05). In addition, weak correlations
      were noted between glycosuria and "medullary" procollagen alpha 1(I) levels (r =
      0.38, P less than 0.05). In situ hybridization studies localized the increased
      procollagen alpha 1(IV) mRNA levels predominantly in the DM group primarily in
      the deep cortex and medullary outer stripe of proximal tubules. Glomerular
      procollagen alpha 1(IV), alpha 1(I), alpha 1(III) and beta-actin mRNA levels were
      not increased in untreated diabetic rats 7 or 28 days after diabetes induction.
      Thus, tubular procollagen alpha 1(IV) mRNA levels increased prior to any
      measurable change in glomerular levels and were ameliorated by insulin
      administration.

PMID- 1381005
TI  - Glomerular size-selectivity and microalbuminuria in early diabetic glomerular
      disease.
AB  - Sieving coefficients of uncharged dextrans of graded size (radii 30 to 60 A) were
      used to characterize barrier size-selectivity in nonazotemic diabetic humans with
      microalbuminuria (Group 1, N = 11) or macroalbuminuria (Group 2, N = 21).
      Compared to a non-diabetic control group (N = 21) the low radius end of the
      sieving profile was depressed, whereas the high radius end was elevated in each
      diabetic group, more so in Group 2 than Group 1. A heteroporous membrane model
      revealed the major portion of the glomerular barrier to be perforated by
      restrictive pores of approximately 56 A radius in all three groups. However, in
      keeping with a parallel trend for GFR, the relative density of restrictive pores
      was control greater than Group 1 greater than Group 2. The remaining minor
      portion of the barrier was perforated by large, shunt-like pores, the relative
      prominence of which ranked Group 2 greater than Group 1 greater than control.
      Although the hypothetical, fractional clearance of macromolecules attributable to
      the shunt-like pores varied directly with fractional clearances of albumin and
      IgG, the progressive increment in the latter fractional protein clearances in the
      two diabetic groups was disproportionate. This raises the possibility that
      factors in addition to barrier size defects contribute to the development,
      magnitude and composition of proteinuria early in the course of diabetic
      glomerular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381006
TI  - Mesangial expression of intercellular adhesion molecule-1 in primary
      glomerulosclerosis.
AB  - Frozen sections of renal biopsy specimens from eight patients with primary focal
      segmental glomerulosclerosis (FSGS) and 10 patients with membranous nephropathy
      (MN) were stained in immuno-peroxidase with the intercellular adhesion molecule-1
      (ICAM-1) monoclonal antibody (MoAb), CL203.4. ICAM-1 was expressed by mesangial
      cells in six patients with FSGS. On the other hand, ICAM-1 was not detected in
      mesangial cells in patients with MN or in the non-affected portion of tumoral
      kidneys used to control normal renal expression of ICAM-1. De novo mesangial
      expression of ICAM-1 in FSGS suggests that sclerosis results from an inflammatory
      process, possibly associated with local release of cytokines.

PMID- 1381007
TI  - Prevention of catecholamine-induced cardiac damage and death with a nucleoside
      transport inhibitor.
AB  - The effect of a potent and specific nucleoside transport inhibitor, R 75,231, on
      catecholamine-induced cardiac toxicity has been studied in rabbits. Epinephrine
      (1 mg/kg) or norepinephrine (2.5 mg/kg) subcutaneously were lethal in 25 (42%) of
      60 control animals, while survivors showed major myocardial damage, as judged
      from high plasma lactate dehydrogenase (LDH) and its myocardial isoenzyme (LDH1)
      after 24 h. When a low dose of R 75,231 (0.1 mg/kg) was given intravenously
      either 1 h before or 1 h after the catecholamine insult, only 1 of 60 animals
      died. The plasma total LDH and the LDH1 myocardial isoenzyme were low in these
      animals compared with untreated survivors. Studies ex vivo on isolated perfused
      hearts confirmed that with treatment using R 75,231, there was both left
      ventricular nucleoside retention and functional preservation after in vivo
      exposure of the animals to epinephrine. R 75,231 did not affect the peripheral
      venous hyperglycemic response to epinephrine. Nucleoside transport inhibition
      offers a new approach to the prevention and treatment of several cardiac
      disorders characterized by a pathogenic effect of catecholamines.

PMID- 1381008
TI  - Effects of probucol on impaired cardiac performance and lipid metabolism in
      streptozotocin-induced diabetic rats.
AB  - Plasma lipids and cardiac performance were studied in diabetic rats treated with
      probucol. Male Wistar rats were rendered diabetic with a single intraperitoneal
      injection of streptozotocin (STZ, 75 mg/kg). Nondiabetic control rats received
      the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic
      rats were randomly assigned to probucol-treated or untreated groups. The rats in
      the two probucol-treated groups (control- and diabetic-probucol groups) were fed
      a diet containing 1% probucol (w/w) for 4 weeks. Blood was drawn, and then
      cardiac performance was assessed by the isolated perfused working heart
      technique. Probucol treatment had no effect on the cardiac performance of the
      nondiabetic control rats. The peak left ventricular developed pressure and
      maximum rate of change in left ventricular pressure during systole were
      significantly greater in the probucol-treated diabetic rats than in the untreated
      diabetic rats (p less than 0.05), although cardiac performance did not improve to
      the level in the nondiabetic rats. Plasma cholesterol, free fatty acid, and
      phospholipid were significantly elevated in the untreated diabetic rats, and
      probucol treatment decreased significantly the plasma cholesterol and free fatty
      acid concentrations (p less than 0.05). These data suggest that probucol
      treatment improves plasma lipids and cardiac performance in rats with
      experimental diabetes and may prevent diabetic cardiomyopathy.

PMID- 1381009
TI  - Suppressive effects of R 56865 on triggered propagated contractions and triggered
      arrhythmias in rat cardiac trabeculae.
AB  - Triggered arrhythmias in rat right ventricular trabeculae are induced by
      triggered propagated contractions (TPCs) that start in damaged regions of the
      muscle and propagate along the preparation. We analyzed the effects of the
      Na+/Ca2+ overload inhibiting agents R 56865 on both TPCs and triggered
      arrhythmias. This compound has been shown to prevent ultrastructural signs of
      intracellular calcium overload and arrhythmias caused by exposure to toxic
      concentrations of cardiac glycosides. TPCs were induced by trains of 15 stimuli
      (2 Hz, 15 s intervals) at 19-21 degrees C and a [Ca2+]o of 1.0-2.5 mM in the
      superfusate. Force was measured with a silicon strain gauge; length and
      shortening of sarcomeres were measured at two sites of the muscle using laser
      diffraction techniques. Exposure to 1.14 x 10(-7) M R 56865 for 30 min decreased
      the force of the last stimulated twitch (twitch force) to 89.7 +/- 4.7% (mean +/-
      SEM) of control, the force produced by TPCs to 39.4 +/- 9.8%, and the velocity of
      propagation of TPCs to 52.8 +/- 6.3%, while TPC latency increased not
      significantly to 104.7 +/- 2.8% of control. R 56865 suppressed TPC force, for the
      same small decrease in twitch force (10%), significantly more than 100 nM D-600
      did (29.5 +/- 2.0 vs. 12.4 +/- 3.1%). Eventually, TPCs disappeared in 8 of 14
      muscles, in 2 of them without any decrease in twitch force. At 5.7 x 10(-7) M, R
      56865 abolished TPCs in five additional trabeculae. An increase in [Ca2+]o
      reintroduced TPCs. During stimulation of 0.5 Hz, 1.14 x 10(-7) M R 56865
      increased the stimulus threshold by 21 +/- 4% in 6 of 14 muscles and decreased
      the twitch force by 26 +/- 3% in 7 of 14 trabeculae. Triggered arrhythmias were
      induced in six muscles with the use of 0.5 mM caffeine or 5 nM Bay K 8644; R
      56865 rapidly terminated these arrhythmias in all muscles. Although the mechanism
      of the antiarrhythmic effects of R 56865 remains to be determined, we speculate
      that the drug raises the threshold for both generation of triggered action
      potentials and calcium-induced calcium release from the sarcoplasmic reticulum.

PMID- 1381010
TI  - Electrophysiologic interactions of procainamide and N-acetylprocainamide in
      isolated canine cardiac Purkinje fibers.
AB  - The study objective was to characterize the electrophysiologic interactions of
      procainamide (PA) and its metabolite, N-acetylprocainamide (NAPA), in canine
      Purkinje fibers. Cell (N = 43) action potentials were measured in Tyrode's
      solution (K+ = 4.0 mM, 36 degrees C) at a basic cycle length of 1,000 ms using
      standard microelectrode techniques. Six PA concentrations (0.020-0.32 mM) and six
      NAPA concentrations (0.010-0.24 mM) were studied alone and in combination. PA
      caused concentration-dependent decreases in Vmax and APD50 but did not alter
      APD90, ERP, or RMP. NAPA caused a small but not significant concentration
      dependent decrease in Vmax, no change in RMP, and significant concentration
      dependent increases in APD50, APD90, and ERP. Low NAPA concentrations increased,
      intermediate concentrations did not affect, and high NAPA concentrations again
      increased PA's effect on Vmax. PA-NAPA combinations resulted in concentration
      dependent changes in APD50 that were intermediate between the effects of PA or
      NAPA alone. PA did not significantly alter NAPA's effects on APD90 at NAPA
      concentrations less than or equal to 0.040 mM, while it antagonized NAPA's effect
      at higher concentrations. The effects of PA-NAPA combinations on ERP were
      generally similar to their effects on APD90. The electrophysiologic effects of PA
      NAPA combinations in normal canine Purkinje fibers are complex functions of the
      relative and absolute concentrations of the two compounds.

PMID- 1381011
TI  - Temporal alterations in peripheral vascular responsiveness during both the
      development and recovery from pacing-induced heart failure.
AB  - The responsiveness of both the in vitro dorsal pedal artery and in vitro
      saphenous vein to alpha-adrenergic agents and prostaglandin F2 alpha was
      evaluated at baseline (prior to the onset of rapid ventricular pacing), at 1 week
      of pacing (mild heart failure), and 4 weeks after pacing when there was recovery
      from congestive heart failure. Eleven dogs were paced at 250 beats/min for 1 week
      and 7 dogs were paced for 3 weeks at 250 beats/min and allowed to recover from
      pacing for a further 4 weeks. At 1 and 4 weeks of recovery, compared to control,
      the maximal responsiveness of the dorsal pedal artery to norepinephrine was
      increased from 5.7 +/- 0.9 to 12.9 +/- 3.3 and 18.6 +/- 1.0 g/mm2, respectively.
      A similar finding was observed in the saphenous vein. The response of the artery
      to the selective alpha 1-agonist, phenylephrine, was also enhanced at 1 week.
      Moreover, the response of the artery and vein to phenylephrine was enhanced
      further at 4 weeks of recovery. In contrast, the response to the selective alpha
      2-agonist, BHT 920, remained unaltered at these time points compared to control.
      Oxymetazoline, an agent used to differentiate between alpha 1-subdivisions,
      produced a significantly higher maximal response at 4 weeks of recovery (18.4 +/-
      1.6 g/mm2 for the artery and 27.7 +/- 2.6 g/mm2 for the vein) compared to control
      (8.2 +/- 0.5 g/mm2 for the artery and 10.3 +/- 0.8 g/mm2 for the vein). The
      artery also displayed lower EC50 values for norepinephrine and phenylephrine at 1
      week (0.7 and 2.2 microM, respectively) and 4 weeks of recovery (0.9 and 3.1
      microM, respectively) compared to control (6.0 and 9.0 microM, respectively). In
      contrast, the only significant decreases in EC50's in the vein were the
      norepinephrine and oxymetazoline at 1 week of pacing (0.2 and 0.06 microM,
      respectively) compared to control (1.5 and 0.09 microM, respectively). The
      maximal tension developed to PGF2 alpha was enhanced after 1 week of pacing in
      both vessels and persisted 4 weeks following the cessation of pacing. Compared
      with control, EC50 values for PGF2 alpha were decreased at 1 and 4 weeks of
      recovery. We conclude that differences exist in peripheral vascular reactivity to
      both alpha 1-adrenoceptor agents and PGF2 alpha at 1 week of pacing and 4 weeks
      of recovery from pacing. Furthermore, the subtle reactivity differences between
      the artery and vein reflect different populations of alpha 1-adrenoceptors
      possibly associated with different signal transduction processes.

PMID- 1381012
TI  - Comparison of the cardiac and hemodynamic effects of lisinopril and atenolol in
      patients with hypertension: therapeutic implications.
AB  - The antihypertensive and hemodynamic effects of lisinopril and atenolol were
      evaluated in 21 patients with mild-to-moderate essential hypertension. Left
      ventricular systolic and diastolic performances were assessed prior to and
      following treatment by first-pass radionuclide cineangiography at rest and during
      peak upright bicycle exercise. Both lisinopril and atenolol treatment
      significantly reduced the blood pressure. Lisinopril therapy was associated with
      a reduction in systemic vascular resistance and left ventricular end-diastolic
      and end-systolic volumes but no change in stroke volume, cardiac output, peak
      ejection rate, peak filling rate, time to peak ejection rate, or time to peak
      filling rate. In contrast, atenolol therapy was associated with an increase in
      end-diastolic volume and stroke volume but no change in cardiac output; the left
      ventricular peak ejection and peak filling rates were decreased by atenolol
      treatment. Although both lisinopril and atenolol each significantly reduced the
      blood pressure, lisinopril had no effect on left ventricular systolic or
      diastolic performance; in contrast, atenolol decreased both systolic and
      diastolic parameters of ventricular performance. Left ventricular function may be
      affected in significantly different ways despite apparent similarities in blood
      pressure control in patients who respond to angiotensin converting enzyme
      inhibition or beta-adrenergic receptor blockade. Differences in hemodynamic
      response to an antihypertensive agent may be important in the selection of a drug
      for the treatment of subsets of patients with cardiac function abnormalities.

PMID- 1381013
TI  - The effects of aging on the electrophysiologic and hemodynamic responses to
      nifedipine in isolated perfused hearts.
AB  - Age effects on responses to calcium channel blockade with nifedipine were studied
      in isolated Langendorff-perfused Fischer 344 rat hearts. Responses to 25 min of
      perfusion with nifedipine concentrations of 0, 25, 50, 75, and 100 ng/ml were
      studied in hearts from 11 mature (6 months) and 13 senescent (23-27 months) male
      F344 rats. Nifedipine produced significant increases in the atrial cycle length
      (p less than 0.001), paced atrioventricular (AV) conduction time (p less than
      0.001), AV Wenckebach cycle length (p less than 0.001), left ventricular (LV)
      diastolic pressure (p less than 0.001), and decreases in LV systolic pressure (p
      less than 0.001) and peak dP/dt (p less than 0.001) in hearts from both mature
      and senescent rats. Greater decreases in the atrial rate (p less than 0.05) and
      depression of peak dP/dt (p less than 0.05) were detected in senescent vs. mature
      rat hearts. No age difference in responses of AV conduction parameters were
      detected although increases in the AV Wenckebach cycle length appeared to be
      greater in senescent hearts at concentrations greater than 75 ng/ml.

PMID- 1381014
TI  - The lazaroid U74006F, a 21-aminosteroid inhibitor of lipid peroxidation,
      attenuates myocardial injury from ischemia and reperfusion.
AB  - U74006F, a novel new 21-aminosteroid inhibitor of lipid peroxidation, has been
      effective in preventing free-radical-mediated injury in central nervous system
      models. To assess its ability to diminish myocardial injury due to ischemia and
      reperfusion, U74006F (n = 11) or its vehicle (n = 11) were administered
      intravenously to New Zealand white rabbits. After allowing for distribution, the
      hearts were excised and exposed to 30 min of stop-flow ischemia and 30 min of
      reperfusion on a nonrecirculating Langendorf apparatus. There was diminished
      creatine phosphokinase release; improved peak positive dP/dt, developed pressure,
      and peak negative dP/dt; and diminished diastolic pressure in the group treated
      with U74006F. Thus, pretreatment with U74006F diminished myocardial injury and
      enhanced systolic and diastolic functional recovery, probably by protecting the
      lipid component of cell membranes from peroxidation by reactive oxygen
      metabolites.

PMID- 1381015
TI  - Rapid infusions of bidisomide or disopyramide in conscious dogs: effect of
      myocardial infarction on acute tolerability.
AB  - The acute tolerability of rapid infusions of bidisomide or disopyramide was
      evaluated in normal conscious dogs and in conscious dogs 48 h after the creation
      of myocardial infarctions (MIs). Both drugs were given in total doses of 15 mg/kg
      (1.5 x the canine antiarrhythmic dose for each drug). Bidisomide was well
      tolerated at infusion rates of 3, 5, 11, and 15 mg/kg/min by normal dogs.
      Disopyramide was well tolerated, except for anticholinergic effects, by normal
      dogs given infusions at rates of 1.5 and 3 mg/kg/min. Disopyramide caused a
      ventricular arrhythmia at 4.5 mg/kg/min in one dog, however. Bidisomide (15
      mg/kg/min) was well tolerated and antiarrhythmic in dogs with infarctions.
      Disopyramide (3 and 4.5 mg/kg/min) was lethal in dogs that had myocardial
      infarctions. A 1 mg/kg/min infusion rate of disopyramide was antiarrhythmic and
      well tolerated, except for anticholinergic effects, in the post-MI dogs. Both
      drugs prolonged the ECG lead II P duration, PR interval (bidisomide more so than
      disopyramide), and QRS duration. Both bidisomide and disopyramide shifted the
      mean electrical axis of the QRS complex from a right axis deviation to the normal
      range in dogs with infarctions. The data indicated that the desired cardiac
      electropharmacologic effects of bidisomide can be achieved in a 1 min infusion.
      Normal dogs, and especially dogs with infarctions, revealed the potential hazards
      of rapidly infusing disopyramide.

PMID- 1381016
TI  - Effect of calmodulin and protein kinase C inhibitors on globally ischemic rat
      hearts.
AB  - Several calmodulin inhibitors have been reported to be cardioprotective, but the
      ability of these compounds to inhibit protein kinase C (PKC) suggests that
      calmodulin inhibition may not be the sole mechanism responsible. To distinguish
      between the effects, we determined the cardioprotective activity of several
      calmodulin inhibitors with differing PKC inhibitory potencies in isolated
      globally ischemic rat hearts. Twenty-five minutes of global ischemia caused
      significant myocardial dysfunction, contracture formation, and lactate
      dehydrogenase (LDH) release on reperfusion in vehicle-treated hearts. The
      calmodulin inhibitors trifluoperazine, W-7, calmidazolium, W-13, and CGS 9343B
      improved postischemic contractile function and/or reduced LDH release. They also
      reduced preischemic cardiac function, although cardioprotection did not appear to
      be correlated with cardiodepression. Calmodulin inhibitors increased preischemic
      coronary flow (CF) and decreased heart rate (HR), but controlling these
      parameters did not affect the cardioprotection. Pretreatment of ischemic hearts
      with trifluoperazine was associated with preservation of myocardial ATP.
      Pretreatment of ischemic rat hearts with the PKC inhibitors staurosporine,
      calphostin C, polymyxin B, and H-7 did not result in cardioprotection. Thus,
      calmodulin inhibition causes cardioprotection that appears to be independent of
      PKC inhibition.

PMID- 1381017
TI  - Profile of cardiovascular effects of NKH477, a novel forskolin derivative,
      assessed in isolated, blood-perfused dog heart preparations: comparison with
      isoproterenol.
AB  - Cardiac and coronary vasodilator effects of NKH477, a novel water-soluble
      forskolin derivative, and isoproterenol, a nonselective beta-adrenoceptor full
      agonist, were compared in isolated, blood-perfused papillary muscle, sinoatrial
      (SA) node, and atrioventricular (AV) node preparations of dogs. Both agents were
      injected intraarterially. The two agents increased the force of contraction of
      the paced papillary muscle and of the unpaced muscle, and the rate of
      automaticity of the latter. They increased sinus rate and accelerated AV nodal
      conduction. In producing these cardiac effects, both agents were similar,
      although NKH477 was 120-350 times less potent than isoproterenol; however, NKH477
      differed distinctly from isoproterenol in that the former increased coronary
      blood flow more greatly than the latter. Thus, NKH477 is more coronary
      vasodilatory than positive inotropic, and more positive inotropic than positive
      chronotropic. Such a cardiovascular profile of NKH477 was similar to that of
      forskolin, except for the duration of actions; NKH477 was longer-acting than
      forskolin.

PMID- 1381018
TI  - Comparison of the effect of celiprolol and nifedipine on blood pressure and
      plasma lipids.
AB  - During a double-blind, randomized study in hypertensive patients, changes in
      blood pressure (BP) and in plasma lipid and lipoprotein levels during treatment
      with celiprolol were compared with those occurring during nifedipine treatment.
      Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension,
      aged 20-64 years, were studied. After a 1-month placebo run-in period, patients
      were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol
      (200 mg daily) each time using a double dummy technique. After 6 weeks, dosages
      of each drug could be doubled. Both drugs caused similar reductions in blood
      pressure but after 12 weeks treatment, the percentage of decrease in diastolic BP
      (DBP) was more pronounced (p less than 0.01) in the nifedipine group (-18%) than
      in the celiprolol group (-12%). After 6 weeks, there were no differences in
      plasma lipids between the two treatment groups. However, the changes after 12
      weeks treatment were different (p less than 0.05) between the groups, leading to
      lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL)
      cholesterol and apoprotein AI, AII, and B in the celiprolol group. Plasma
      lecithin cholesterol acyltransferase activity (LCAT) was not modified, suggesting
      that reverse cholesterol transport was not affected by the drugs. In both
      treatment groups, a significant positive relationship was observed between
      changes in LDL cholesterol and apoprotein B. As compared with nifedipine,
      celiprolol after 12-week therapy had a rather favorable plasma lipid profile. The
      clinical relevance of such findings, in terms of prevention of cardiovascular
      complications, has yet to be established.

PMID- 1381019
TI  - Vasodilator therapy for acute heart failure: haemodynamic comparison of
      hydralazine/isosorbide, alpha-adrenoceptor blockade, and angiotensin-converting
      enzyme inhibition.
AB  - Haemodynamic comparison of three vasodilation regimens [intravenous (i.v.)
      hydralazine and isosorbide dinitrate (ISDN) combined, i.v. doxazosin, and i.v.
      enalaprilat] was undertaken in 36 patients with acute left ventricular (LV)
      failure due to recent myocardial infarction. Each regimen achieved similar
      reductions in pulmonary artery occluded pressure (PAOP, preload) and systemic
      arterial pressures (afterload), with increased cardiac and stroke volume (SV)
      indexes (p less than 0.01). Only the hydralazine and isosorbide combination
      induced resting tachycardia. Balanced vasodilatation after selective alpha
      adrenoceptor blockade (doxazosin) and angiotensin-converting enzyme (ACE)
      inhibition (enalaprilat) without increase in heart rate (HR) suggests that these
      therapies may have definite haemodynamic advantages over the hydralazine/ISDN
      combination.

PMID- 1381020
TI  - Comparison of peptide and nonpeptide receptor-mediated responses in rat tail
      artery.
AB  - Chronic uremia and metabolic acidosis impair vascular responses to norepinephrine
      (NE) and also cause multiple metabolic defects in skeletal muscle. These studies
      were conducted to determine whether decreased vascular responsiveness resulted
      from putative second messenger metabolism. Tail arteries were used from rats with
      metabolic acidosis or nonacidotic uremia and from normal controls. In normal
      arteries, the maximal responses were the same for arginine vasopressin (AVP), NE,
      and mixtures of the two agonists, suggesting that the two receptor types use the
      same transduction mechanism. Nonetheless, qualitative differences exist between
      AVP- and NE-induced responses: (a) Concentration-response curves are steeper for
      AVP than for NE, (b) EC50 values are similar for AVP between inositol phosphates
      (IP assays) and contraction, but not for NE, and (c) arteries from rats with
      metabolic acidosis or uremia show selective blunting of biochemical and
      contractile responses to NE but not to AVP. We conclude that these metabolic
      derangements selectively affect alpha-adrenergic receptors, but not AVP receptors
      or the transduction mechanism leading to contraction.

PMID- 1381021
TI  - Dexamethasone potentiates production of inositol trisphosphate evoked by
      endothelin-1 in vascular smooth muscle cells.
AB  - To investigate the possibility of participation of glucocorticoids in the action
      of endothelin-1 (ET-1), the effect of glucocorticoids on ET-1-induced inositol
      trisphosphate (IP3) production was studied in cultured vascular smooth muscle
      cells (VSMC). ET-1 transiently increased IP3 in a dose-dependent manner.
      Pretreatment with 1 microM dexamethasone for 48 h shifted the dose-response curve
      of ET-1-induced IP3 production to the left; i.e., it significantly reduced the
      half-maximal effective concentration of ET-1 (from 50 to 10 nM). This action of
      dexamethasone required a minimum of 12 h of incubation. A glucocorticoid
      antagonist, RU 38486, completely blocked this effect. To elucidate the
      interaction with prostaglandin, we used indomethacin, a potent inhibitor of
      prostaglandin synthesis. Treatment with 1 microM indomethacin shifted the dose
      response curve of ET-1-induced IP3 production to the left, but this shift was
      significantly less than that observed after treatment with dexamethasone and no
      additive effect between indomethacin and dexamethasone was noted. Glucocorticoids
      potentiate the IP3 production response to ET-1 in cultured VSMC, and this action
      of glucocorticoids depends partially on prostaglandin inhibition. These results
      suggest that glucocorticoids play an important role in modulation of ET-1 action.

PMID- 1381023
TI  - Differential effects of quinidine on transmembrane action potentials of normal
      and infarcted canine Purkinje fibers.
AB  - Fourteen days after proximal ligation of the left anterior descending coronary
      artery (LAD) of mongrel dogs, the effects of quinidine on action potentials of
      normal and infarcted Purkinje fibers were evaluated. The concentration-dependent
      (10(-7)-3 x 10(-5) M) and frequency-dependent (1 and 3 Hz) actions of quinidine
      were evaluated by the following parameters: maximum upstroke velocity (Vmax),
      action potential duration at 50 and 95% repolarization (APD50, APD95), effective
      refractory period (ERP), resting membrane potential (RMP), and action potential
      amplitude (APA). Quinidine reduced Vmax in normal and abnormal Purkinje fibers in
      a concentration- and frequency-dependent manner; these effects were more
      pronounced in infarcted tissue. The APD50 was shortened significantly at 1 Hz in
      noninfarcted Purkinje fibers, whereas in infarcted Purkinje fibers quinidine had
      no effect on APD50. The APD95 was not significantly altered by quinidine in
      normal Purkinje fibers; in infarcted areas APD95 was significantly prolonged at 1
      and 3 Hz. The effective refractory period (ERP) was prolonged in normal and
      infarcted Purkinje fibers, these effects were more marked in ischemically damaged
      fibers. No effects were observed on resting membrane potential (RMP). APA was
      reduced significantly after quinidine at 1 and 3 Hz; there was no difference
      between normal and infarcted tissue. These data indicate a differential effect of
      quinidine in normal and infarcted Purkinje fibers which may be an important
      mechanism of action of quinidine in infarcted tissue.

PMID- 1381022
TI  - Efficacy and tolerability of isradipine and metoprolol in treatment of
      hypertension: the Finnish Isradipine Study in Hypertension (FISH).
AB  - Eight hundred seventy-six men and women with diastolic blood pressure (DBP) of 95
      115 mm Hg during a 4-week placebo period were included in a multicenter trial;
      479 patients had previously been treated for hypertension. The patients were
      randomized to receive isradipine or metoprolol; both groups were comparable for
      age, weight, height, smoking habits, and duration of hypertension. By the end of
      the placebo period, 79 patients did not fulfill the final entry criteria and were
      withdrawn. The isradipine group consisted of 398 patients (164 women and 234
      men), and the metoprolol group consisted of 399 patients (173 women and 226 men).
      The initial dose of isradipine was 1.25 mg twice daily (b.i.d.), and the initial
      dose of metoprolol was 50 mg b.i.d.; the doses were doubled after 4 weeks if DBP
      had not decreased to less than or equal to 90 mm Hg. After 8 weeks, the
      isradipine group began combination therapy with metoprolol 50 mg b.i.d. and the
      metoprolol group began combination therapy with isradipine 1.25 mg b.i.d. if DBP
      was not less than or equal to 90 mm Hg. After 8 weeks monotherapy, mean BP (MBP)
      was reduced by 13/11 mm Hg (161/104 to 148/93) in the isradipine group and by
      15/12 mm Hg (160/103 to 145/91) in the metoprolol group. Monotherapy with
      isradipine normalized DBP to less than or equal to 90 mm Hg in 52% with a mean
      dose of 4.26 mg daily, and monotherapy with metoprolol normalized DBP in 58% with
      a mean dose of 155 mg daily.1+

PMID- 1381024
TI  - Twenty-four-hour beta-blockade in stable angina pectoris: a study of atenolol and
      betaxolol.
AB  - We examined the importance of a long plasma half-life (t1/2) on the antianginal
      effects of beta-blockade by comparing equivalent doses of once-daily atenolol 100
      mg (t1/2 6-8 h) and betaxolol 20 mg (t1/2 20-22 h) in a double-blind placebo
      controlled cross-over study of 20 patients with stable angina pectoris. At 20 h
      postdose, heart rate (HR) was lower with betaxolol than with atenolol whereas
      blood pressure (BP) was equally reduced by both drugs. Twenty-four-hour
      ambulatory HR recording demonstrated that this difference existed for the last 6
      h of the dosage cycle. During treadmill exercise, HR remained lower with
      betaxolol than with atenolol and exercise time was significantly prolonged only
      by betaxolol. With placebo, radionuclide ventriculography demonstrated that left
      ventricular ejection fraction (LVEF) decreased during exercise. Betaxolol, but
      not atenolol, significantly attenuated the exercise-induced decrease in EF. Thus,
      the long plasma t1/2 of betaxolol is associated with a reduction in exercise
      induced ischemia when tested toward the end of the 24-h dosage cycle. Plasma t1/2
      therefore is of clinical relevance to the antianginal, but not antihypertensive,
      actions of beta-blockers.

PMID- 1381025
TI  - Cardiac responses after norepinephrine-induced ventricular hypertrophy in rats.
AB  - The increase in norepinephrine (NE) blood levels in human heart failure
      correlates with prognosis. In this study, we determined whether continuous NE
      infusion alters the positive inotropic and chronotropic responses of isolated rat
      cardiac muscles. Osmotic minipumps were implanted subcutaneously (s.c.) in 43
      adult male rats to deliver NE (160 micrograms/kg/h for 14 days); 42 rats were
      sham-operated. Isolated left and right atria and left and right ventricular (LV,
      RV) papillary muscles were prepared to measure positive inotropic or chronotropic
      responses to NE, phenylephrine, forskolin, dibutyryl cyclicAMP (dbcyclicAMP), and
      calcium chloride. NE infusion caused (a) a 22% increase in LV wet weight without
      altering atrial or RV wet weights; (b) an 18% decrease in maximal inotropic
      response to calcium chloride in LV papillary muscles only; (c) a significantly
      decreased peak response to NE [72 +/- 5 vs. 93 +/- 5% (sham rats) of calcium
      chloride] but not to forskolin or dbcyclicAMP in RV papillary muscles; (d) an
      increased incidence of ectopy at low concentrations of NE, forskolin, and
      dbcyclicAMP in LV papillary muscles; (e) no alteration in papillary muscle
      responses to phenylephrine but significantly increased left atrial inotropic
      responses [51 +/- 5 vs. 33 +/- 2% (sham rats) of calcium chloride] and right
      atrial chronotropic responses [30 +/- 2 vs. 18 +/- 4 (sham rats) beats/min]; and
      (f) a selective decrease in beta 1-adrenoceptor density in both ventricles. Thus,
      NE infusion causes selective LV hypertrophy; responses of compounds that increase
      intracellular cyclicAMP are affected to a greater extent in papillary muscles
      from the hypertrophied ventricle than in tissues from the other chambers of the
      heart.

PMID- 1381026
TI  - Stereoselective interactions of (R)- and (S)-propafenone with the cardiac sodium
      channel.
AB  - The specific interactions of both (R)- and (S)-propafenone with the cardiac
      sodium channel were studied with patch clamp techniques in the whole-cell
      recording mode at reduced extracellular Na+ on guinea pig ventricular cells. Both
      (R)- and (S)-propafenone (10 microM) shifted the membrane potential required for
      half-maximal steady-state inactivation (E0.5) of the cardiac sodium channel to
      considerably more negative membrane potentials [E0.5 = -70.8 +/- 2.9 mV for
      controls vs. -85 +/- 3.1 mV for (R)-propafenone and -91.9 +/- 1.7 mV for (S)
      propafenone]. (S)-Propafenone at a concentration of 10 microM is more effective
      in shifting the h infinity curve of the cardiac sodium channel. Recovery from
      inactivation of the cardiac sodium current is prolonged by orders of magnitude by
      both stereoenantiomeric forms [time constants were estimated to be 38 +/- 15 ms
      at -90 mV vs. 46.5 +/- 14.3 s for (R)-propafenone and 74.2 +/- 37.9 for (S)
      propafenone]. Development of block occurs mainly through the inactivated channel
      conformation for both (R)- and (S)-propafenone. Development of block of
      inactivated cardiac sodium channels occurs with time constants of 15.9 +/- 3.9 s
      for (R)-propafenone and 19.7 +/- 7.3 s for (S)-propafenone at 10 microM. Action
      potential duration and possible stereoselective interaction with ion transport
      systems other than sodium channels may influence the block developed by either
      (R)- or (S)-propafenone at a given concentration and beating frequency indirectly
      through the membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381027
TI  - Central action of atropine on cardiovascular reflexes in humans.
AB  - Effects of exciting the central nervous system (CNS) with low doses of atropine
      on cardiovascular reflexes was investigated in 6 healthy volunteers. Cumulative
      doses of atropine sulfate (1.43-28.57 micrograms/kg intravenously, i.v.) were
      used. The ECG parameters used to quantify the nervous activities on the heart
      were ratios of the longest to the shortest R-R intervals recorded during forced
      expirations and deep inspirations (respiratory sinus arrhythmia), the ratio of
      the longest to the shortest R-R intervals which occur immediately after one rises
      from a low sitting position (30:15 ratio), and the SD of R-R intervals recorded
      in standing and supine positions. Very low doses of atropine (1-3 micrograms/kg)
      increased the 30:15 ratios from (means +/- SEM) 1.21 +/- 0.07 to 1.34 +/- 0.04
      (60% increase, p less than 0.01) and SD recorded in standing positions from 32.4
      +/- 3.5 to 56.0 +/- 11.0 ms (71% increase, p less than 0.01). Respiratory sinus
      arrhythmia was not affected in either the standing or supine position, nor was SD
      recorded in supine positions significantly affected by these low doses of
      atropine. The only indexes increased by low doses of atropine were those that
      measure cardiovascular responses to active standing, consistent with an increased
      excitability of the medullary cardiovascular (vasomotor) centre. There was no
      evidence of central vagal excitation caused by low doses of atropine in the
      conscious, spontaneously breathing volunteers. The increased excitability of the
      medullary cardiovascular centre in response to a low dose of atropine may suggest
      that normal responses of this centre to arterial baroreceptor stimulation is
      restrained by a cholinergic inhibitory pathway.

PMID- 1381028
TI  - Aprotinin decreases release of 6-keto-prostaglandin F1 alpha and increases
      release of thromboxane B2 in cultured human umbilical vein endothelial cells.
AB  - Use of the proteinase inhibitor aprotinin significantly improves hemostasis and
      reduces bleeding after operations in which extracorporeal circulation is used.
      The mechanism of action, however, has been only partially clarified. In this work
      we investigated whether aprotinin influenced the production and release of the
      eicosanoids prostacyclin, measured as the stable metabolite 6-keto-prostaglandin
      F1 alpha, and thromboxane A2, measured as the stable metabolite thromboxane B2,
      from endothelial cells. Human umbilical vein endothelial cells were incubated
      with different concentrations of aprotinin (5.5, 20, 55, and 100 mumol/L). The
      levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 were measured at
      baseline and after thrombin stimulation. A concentration-dependent effect of
      aprotinin on 6-keto-prostaglandin F1 alpha synthesis was demonstrated. After
      incubation with 100 mumol/L of aprotinin, a 90% reduction in 6-keto-prostaglandin
      F1 alpha production was seen (31.69 versus 307.44 picograms per million cells; p
      less than 0.001). Conversely, thromboxane B2 production showed a 345% increase
      after incubation with aprotinin (287.80 versus 83.82 picograms per million cells;
      p less than 0.0001). Since 6-keto-prostaglandin F1 alpha inhibits and thromboxane
      B2 strongly enhances platelet aggregation, it appears that one mechanism of the
      clinically observed effectiveness of aprotinin lies in the altered ratio of 6
      keto-prostaglandin F1 alpha: thromboxane B2 in endothelial cells, which leads to
      enhanced platelet aggregation and improved vessel sealing.

PMID- 1381029
TI  - Limiting edema in neonatal cardiopulmonary bypass with narrow-range molecular
      weight hydroxyethyl starch.
AB  - The marked edema observed in neonatal cardiopulmonary bypass is thought to result
      from pathologic increases in capillary permeability. Pentafraction is a
      subfraction of hydroxyethyl starch that is thought to be of appropriate size and
      shape to be retained by leaking capillaries and seal endothelial gaps in
      capillary basement membranes. To test the hypothesis that pentafraction would
      reduce edema in neonatal cardiopulmonary bypass, we established a model of edema
      formation in neonatal bypass in which neonatal piglets underwent 2 hours of
      normothermic cardiopulmonary bypass with crystalloid prime and no myocardial
      ischemia. Before initiation of bypass, experimental animals (n = 11) received
      intravenous pentafraction, 3 gm/kg. Control animals (n = 10) received an
      equivalent volume of saline. Hemodynamic parameters, animal weight, fluid
      redistribution, and percent tissue water of individual organs were assessed
      during and after bypass. Pentafraction treatment resulted in significant
      differences in (1) lowered percent body weight gain from baseline (11% versus
      48%), (2) lowered volume requirement to maintain venous reservoir during
      cardiopulmonary bypass (148 ml/kg versus 581 ml/kg), (3) less fluid loss from the
      peritoneum (11 ml/kg versus 115 ml/kg), and (4) lowered percent tissue water of
      kidney, pancreas, stomach, jejunum, colon, and skeletal muscle (p less than 0.05
      by unpaired t test). Pentafraction had no effect on hemodynamic parameters during
      bypass nor in percent tissue water of heart, lung, liver, spleen, skin, or brain.
      In summary, pentafraction lessened weight gain and fluid requirements during
      cardiopulmonary bypass, favorably influencing the percent tissue water of certain
      organs. If pentafraction functions as proposed, it may have wide applicability
      not only in cardiopulmonary bypass (or extracorporeal membrane oxygenation) but
      also in other clinical scenarios with altered capillary permeability.

PMID- 1381030
TI  - Age-dependent ventricular response to pressure overload. Considerations for the
      arterial switch operation.
AB  - Success with the arterial switch operation for D-transposition of the great
      arteries and the concept of left ventricular suitability for systemic work
      stimulated this literature review of the age-dependent mechanisms in normal
      cardiac growth and pressure-induced left ventricular hypertrophy. Normal
      postnatal myocardial growth is markedly influenced by hemodynamic factors. It
      consists of an early hyperplastic phase of both myocytes and capillaries that is
      followed by a myocyte hypertrophic phase. Similarly, imposition of a pressure
      overload induces both myocyte hyperplasia/hypertrophy and increased angiogenesis
      in neonates, but only myocyte hypertrophy at a later age. The functional
      consequences of ventricular hypertrophy are the result of adaptive and
      nonadaptive changes resulting from the overload stimulus, for example, induction
      of protooncogene expression, myosin isoenzyme shifts, degree of coronary
      perfusion, responsiveness to beta-adrenergic stimulation, and myocyte capacity to
      re-accumulate or sequester cytosolic calcium. Strikingly, both the capacity and
      the rapidity of left ventricular hypertrophy decrease with increasing age. This
      experimental information supports the current use of primary arterial switching
      for neonates with D-transposition of the great arteries and the use of "rapid"
      two-stage arterial switching in infants more than 3 to 4 weeks of age; it raises
      some concern about the practice of late retraining of the left ventricle in cases
      of failed atrial inversion operation.

PMID- 1381031
TI  - Implantation of in vitro endothelialized polytetrafluoroethylene grafts in human
      beings. A preliminary report.
AB  - To assess the impact of in vitro endothelialization on prosthetic graft patency,
      we performed femorotibial reconstruction in four patients.
      Polytetrafluoroethylene grafts (6 mm), lined with cultivated autologous
      endothelial cells, harvested from the veins of the forearm, were used. Autologous
      endothelial cells were harvested enzymatically and characterized by morphology
      and factor VII staining. After a cultivation period of 17 to 23 days, the cell
      count increased from 27 +/- 3 x 10(4) endothelial cells to 5.4 +/- 1.1 x 10(6).
      Endothelial cell seeding on polytetrafluoroethylene prostheses was then
      performed. To improve endothelial cell attachment to the graft surface,
      polytetrafluoroethylene grafts (60 to 70 cm; 6 mm diameter) were precoated with
      fibrin glue containing fibrin and fibronectin and the fibrinolysis inhibitor
      aprotinin. Seeding density of 49 +/- 10 x 10(3) endothelial cells per square
      centimeter yielded a preconfluent monolayer immediately after seeding, as
      demonstrated by scanning electron microscopy. A second cultivation period of 6
      days, after seeding and before implantation, was necessary for establishment of a
      confluent monolayer and to allow for maturation of the endothelial cell
      cytoskeleton as well as production and excretion of extracellular matrix. Grafts
      endothelialized in vitro were implanted in four patients requiring femorotibial
      reconstruction. Scintigraphic studies with indium 111-labeled platelets
      demonstrated little or no platelet deposition, indicating persistent
      endothelialization. All grafts remained patent at 3 months after implantation.

PMID- 1381032
TI  - Malignant melanoma metastatic to the right atrium: an asymptomatic solitary
      metastasis diagnosed incidentally by magnetic resonance imaging.

PMID- 1381033
TI  - Kinetics of diffusion in a spherical cell. II. Solute buffering included.
AB  - This paper on diffusion kinetics in neurons presents an analysis of diffusion in
      the presence of solute buffering. Computational rather than theoretical methods
      are usually necessary since buffering generally precludes an analytical solution
      to the diffusion equations. As in the companion paper, our methods are
      illustrated in the context of calcium diffusion in a spherical cell. However, the
      same methods can be applied to the spread of any second messenger and other
      geometries. Analytical or computational predictions of the time course of
      diffusion and buffering may help guide further experiments and simulations. For
      example, simulations of calcium diffusion in a model of the bullfrog sympathetic
      ganglion cell show that buffering at depths greater than 5-6 microns is almost
      instantaneous compared to diffusion from sources at the cell membrane. Since
      buffering complicates the design of multicompartmental models, we demonstrate
      that a few compartments designed on the basis of diffusion alone (Carnevale and
      Rosenthal, 1992) may be a satisfactory framework for a model that includes
      bimolecular buffering. An analytical solution may be possible if the buffering
      reaction can be linearized. We describe a method for linearizing bimolecular
      saturating buffering, i.e., approximating it by a unimolecular non-saturating
      process that immobilizes solute. The analytical solution for the linearized
      reactive diffusion problem fits a non-linear model of calcium movement in the
      bullfrog sympathetic ganglion cell quite well after a few milliseconds.

PMID- 1381034
TI  - Biotinylated dextran amine as an anterograde tracer for single- and double
      labeling studies.
AB  - Fluorescent dextran amines have recently been reported to be useful for
      anterograde pathway tracing. However, fluorescent markers are not always ideal
      for detailed mapping studies. We therefore evaluated the efficacy of a
      biotinylated dextran amine (BDA) for anterograde labeling in several different
      preparations. BDA was visualized with an avidin-biotinylated HRP (ABC) procedure
      followed by a standard or metal-enhanced diaminobenzidine (DAB) reaction. After
      iontophoretic injections of BDA into neocortex-like telencephalic regions in
      pigeons or into visual or somatosensory cortex in rats, there was excellent and
      abundant labeling of axons and terminals in forebrain, midbrain and hindbrain
      target areas with 1-week survival times. Large pressure injections of BDA into
      the avian telencephalon were also found to result in extensive anterograde
      labeling. We then carried out a series of studies using 2-color DAB double
      labeling to determine effective approaches for combining BDA labeling with other
      labeling methods. Using an isolated embryonic chick spinal cord-hindlimb
      preparation, we combined BDA labeling with another anterograde labeling method to
      differentially label two sets of projections. In these studies, sensory neuron
      and motoneuron projections into the limb from the same segmental level, or
      motoneuron projections into the limb from two separate segments were
      differentially labeled by using HRP (visualized first with a blue/black metal-DAB
      reaction) and BDA (visualized second with a brown DAB reaction). In other double
      labeling studies, we combined BDA labeling of axons and terminals with
      immunohistochemical labeling of neurons. In these experiments, telencephalic
      neurons in pigeons or rats were labeled immunohistochemically for parvalbumin or
      substance P (using a brown DAB reaction) and BDA-labeled axons were labeled
      blue/black (using a metal-intensified DAB reaction). Double-labeling was
      successful regardless of whether the entire immunohistochemical labeling
      procedure preceded or followed the BDA labeling procedure. Together, these
      studies show that BDA is effective for anterograde pathway tracing and can be
      used in double-label studies with other labeling methods.

PMID- 1381035
TI  - Antithyroid drugs and release of inflammatory mediators by complement-attacked
      thyroid cells.
AB  - Thyroid cells are exposed to complement attack in Graves' disease and Hashimoto's
      thyroiditis, but are resistant to killing by homologous complement. We have
      examined the effects of sublethal complement attack on thyroid cells in vitro.
      Extracellular reactive oxygen metabolites were produced and prostaglandin E2,
      interleukin-1 alpha, and interleukin-6 were released after complement attack.
      Cells pretreated with interferon-gamma and interleukin-1 alpha, which increase
      expression of CD59, were more resistant to these effects of complement.
      Conversely, blockade of CD59 with monoclonal antibody increased complement
      mediated oxygen radical production and release of prostaglandin E2, interleukin-1
      alpha, and interleukin-6. The antithyroid drugs methimazole and propylthiouracil
      abolished or reduced oxygen radical production by complement-attacked thyroid
      cells and reduced cytokine release. These results suggest that sublethal
      complement attack in autoimmune thyroid diseases exacerbates tissue injury by
      causing thyroid cells to release potent phlogistic mediators, although some
      degree of protection may be afforded in vivo by cytokine-mediated upregulation of
      CD59. Antithyroid drugs, concentrated within thyroid cells, will prevent the
      release of these inflammatory molecules, which may in turn explain the
      amelioration of thyroiditis and remission of Graves' disease after such
      treatment.

PMID- 1381036
TI  - Ventricular arrhythmia and long-term survival with maintenance dialysis.

PMID- 1381037
TI  - Induction of cytokines in human peripheral blood mononuclear cells by
      mycoplasmas.
AB  - Various species of mycoplasmas were tested for their ability to induce cytokine
      production in human peripheral blood mononuclear cells (PBMC). Human PBMC were
      incubated with Mycoplasma pneumoniae, M. hyorhinis, M. arginini, M. salivarium,
      M. orale, M. gallisepticum or A. laidlawii for 48 hr, and the activities of
      interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, tumor necrosis factor-alpha
      (TNF-alpha) and interferon (IFN) in the supernatants were determined by ELISA or
      bioassay. All mycoplasma species induced IL-1 beta, IL-6 and TNF-alpha, although
      IL-2 was induced only by M. pneumoniae. IFN was induced by 5 of the 7 species,
      and the IFN produced was antigenically confirmed to be mainly IFN-alpha. On the
      other hand, mycoplasma-stimulated cultures did not contain detectable amounts of
      IFN-beta and IL-4 activities. Furthermore, the cytokines were induced by
      mycoplasmal contaminating cells in human PBMC as well as by mycoplasma alone.
      These results suggest that many kinds of cytokines induced by mycoplasma
      contamination in cell culture affect immunological experiments in vitro.

PMID- 1381038
TI  - A possible role for nitric oxide in glutamate (MSG)-induced Chinese restaurant
      syndrome, glutamate-induced asthma, 'hot-dog headache', pugilistic Alzheimer's
      disease, and other disorders.
AB  - Endogenous glutamate is thought to be a major neurotransmitter. After binding to
      a cell membrane receptor there can be a stimulation of what can be called the
      nitric oxide (NO)-mediated neurotransmission pathway (NO-MNP). The activity of
      the enzyme that produces NO from arginine, NO synthase, and the level of NO
      become elevated. NO has little activity within the cell in which it is produced,
      but it rapidly leaks out of that cell and produces effects in neighboring cells.
      The NO-MNP can be activated to release NO in endothelial cells which in turn acts
      on neighboring vascular smooth muscle cells to induce vasodilation. Therefore, we
      suggest that exogenous, ingested glutamate, like endogenous glutamate, can lead
      to the same stimulation of the NO-MNP in sensitive individuals which would then
      cause the symptoms of the Chinese restaurant syndrome and/or glutamate-induced
      asthma. Further, since ingested nitrite and related compounds can be metabolized
      to NO, NO may more directly cause the symptoms of 'hot dog headache'. In
      addition, it has been suggested that NO production can also be controlled in
      endothelial cells by fluid forces that stimulate pressure receptors. Therefore,
      elevations of NO and stimulation of the NO-MNP may occur due to sudden, local,
      alterations of blood pressure during pugilistic activities and play a role in the
      symptoms of pugilistic Alzheimer's disease. If these ideas are correct, then
      inhibitors of the NO-MNP and/or temporary reduction of the plasma level of
      arginine may be useful in preventing at least some of the symptoms of these
      disorders.

PMID- 1381039
TI  - Update: cholera--western hemisphere, 1992.

PMID- 1381040
TI  - Update: eradication of paralytic poliomyelitis in the Americas.
AB  - On August 23, 1991, a 2-year-old boy in the district of Junin, Peru, had onset of
      symptoms of culture-confirmed paralytic poliomyelitis. This is the last case of
      paralytic poliomyelitis with a wild poliovirus isolate reported to the Pan
      American Health Organization (PAHO) and the first time since reporting of
      poliomyelitis began in the Western Hemisphere that no such paralytic disease has
      been detected for an entire year. This report updates the poliomyelitis
      eradication effort in the Americas.

PMID- 1381041
TI  - Metabotropic glutamate receptors potentiate ionotropic glutamate responses in the
      rat dorsal horn.
AB  - The effects of the metabotropic glutamate receptor agonist (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] were examined on responses
      mediated by the ionotropic glutamate receptor agonists N-methyl D-aspartate
      (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), and
      kainic acid (KA), in neurons acutely isolated from the dorsal horn of the rat
      spinal cord. (1S,3R)-ACPD produced an increase in the intracellular Ca2+
      concentration in 50% of acutely isolated dorsal horn neurons, which could be
      prevented by blockers of voltage-sensitive Ca2+ channels. (1S,3R)-ACPD markedly
      potentiated increases in the intracellular Ca2+ concentration induced by NMDA,
      AMPA, and KA but not by 10-50 mM KCl. This potentiation occurred in all cells,
      required the simultaneous presence of both agonists, and was rapidly reversible.
      In the spinal cord slice preparation, (1S,3R)-ACPD potentiated the inward
      currents evoked by pressure application of AMPA, NMDA, and KA, an effect that was
      also rapidly reversible. These short term effects of (1S,3R)-ACPD may play an
      important role in the regulation of ionotropic responses mediated by glutamate in
      the spinal cord.

PMID- 1381042
TI  - Biochemical characterization of kainate receptors from goldfish brain.
AB  - Kainate receptors from goldfish brain were purified by affinity chromatography.
      Unlike previously published purifications, which have yielded single proteins of
      48-50 kDa from frog, chick, and pigeon brain, our preparations contained two
      polypeptides, of 41 kDa and 45 kDa. In addition, a broad band centered at 120 kDa
      was present. Some of the 41-kDa and 45-kDa polypeptides were derived from the
      higher molecular mass protein. All of these proteins were recognized by a
      monoclonal antibody produced against a purified frog kainate receptor. The
      distribution of the 41-kDa and 45-kDa proteins varied independently in different
      major brain regions, suggesting that they can exist as separate independent
      proteins. A partial amino acid sequence of the 41-kDa polypeptide is very similar
      (40-60% identity) to specific segments of the frog and chick kainate-binding
      proteins and the alpha-amino-3-hydroxy-5-methylisoxazolepropionate/kainate ion
      channels. The characteristics of the 41-kDa and 45-kDa polypeptides suggest that
      these two proteins are distinct. Photo-affinity labeling with [3H]kainate showed
      that a [3H]kainate binding site is associated with the 41-kDa polypeptide, and
      peptide mapping suggests that the two proteins are not identical. In addition,
      the two peptides do not appear to be related by differential glycosylation or
      phosphorylation. The 41-kDa and 45-kDa polypeptides, therefore, appear to be
      distinct and may represent kainate receptor subtypes or, in some cases, possibly
      two different subunits of a kainate receptor complex.

PMID- 1381043
TI  - Histamine increases cytosolic Ca2+ in dibutyryl-cAMP-differentiated HL-60 cells
      via H1 receptors and is an incomplete secretagogue.
AB  - Human neutrophils and dibutyryl-cAMP (Bt2cAMP)-differentiated HL-60 cells possess
      receptors for the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L
      phenylalanine (fMet-Leu-Phe), which mediate activation of phospholipase C, with
      subsequent increase in cytosolic Ca2+ concentration ([Ca2+]i) and activation of
      specific cell functions. In many cell types, histamine, via H1 receptors,
      activates phospholipase C, but it is unknown whether neutrophilic cells possess
      functional H1 receptors. We compared the effects of histamine with those of fMet
      Leu-Phe on activation of these cells. In Bt2cAMP-differentiated HL-60 cells,
      substances increased [Ca2+]i in the effectiveness order fMet-Leu-Phe greater than
      histamine greater than betahistine. Pertussis toxin diminished fMet-Leu-Phe
      induced rises in [Ca2+]i to a greater extent than those induced by histamine. H1
      but not H2 antagonists inhibited histamine- and betahistine-induced rises in
      [Ca2+]i. fMet-Leu-Phe and histamine activated phospholipase C and increased
      [Ca2+]i through release of Ca2+ from intracellular stores and sustained influx of
      Ca2+ from the extracellular space. The substances also induced Mn2+ influx. Ca2+
      and Mn2+ influxes were inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxyl]-4
      methoxyphenethyl)-1H-imida zole hydrochloride (SK&F 96365). The stimulatory
      effects of histamine on [Ca2+]i were more sensitive to inhibition by 4 beta
      phorbol 12-myristate 13-acetate than were those of fMet-Leu-Phe. Unlike fMet-Leu
      Phe, histamine did not activate superoxide anion formation, release of beta
      glucuronidase, and tyrosine phosphorylation. In neutrophils, histamine and
      betahistine did not induce rises in [Ca2+]i. Our data show that (i) in Bt2cAMP
      differentiated HL-60 cells, histamine increases [Ca2+]i via H1 receptors coupled
      to pertussis toxin-sensitive and possibly, pertussis toxin-insensitive
      heterotrimeric regulatory guanine nucleotide-binding proteins, (ii) histamine
      activates nonselective cation channels, and (iii) unlike fMet-Leu-Phe, histamine
      is an incomplete secretagogue.

PMID- 1381044
TI  - Histamine increases cytosolic Ca2+ in HL-60 promyelocytes predominantly via H2
      receptors with an unique agonist/antagonist profile and induces functional
      differentiation.
AB  - Histamine H1 receptors mediate activation of phospholipase C, with subsequent
      increases in cytosolic Ca2+ concentration ([Ca2+]i), and H2 receptors mediate
      accumulation of cAMP. HL-60 promyelocytes possess H2 receptors, but it is not
      known whether these cells also possess H1 receptors. We studied the effects of
      histamine on [Ca2+]i and the functional importance of histamine receptors in HL
      60 promyelocytes. In these cells, histamine and dimaprit increased [Ca2+]i with
      EC50 values of 15 microM and 30 microM, respectively. Diphenhydramine inhibited
      the effect of histamine (100 microM) on [Ca2+]i up to 40%, with an IC50 of 100
      nM. Famotidine and cimetidine diminished the effect of histamine (100 microM) up
      to 75%, with IC50 values of 85 nM and 300 nM, respectively. Diphenhydramine plus
      famotidine abolished histamine-induced rises in [Ca2+]i. Impromidine, with an
      IC50 of 100 nM, abolished the effect of histamine (100 microM) on [Ca2+]i.
      Diphenhydramine, famotidine, cimetidine, and impromidine showed marked
      noncompetitive antagonism with histamine. Histamine-induced increases in [Ca2+]i
      were largely due to influx of Ca2+ from the extracellular space. Ca2+ influx was
      inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl)-1H-imida
      zole hydrochloride (SK&F 96365). Histamine activated phospholipase C. Histamine
      induced expression of formyl peptide receptors, which effect was abolished by
      famotidine. In U-937 promonocytes and in the human erythroleukemia cell lines HEL
      and K-562, histamine did not induce rises in [Ca2+]i. Our data suggest the
      following. (i) In HL-60 promyelocytes, histamine increases [Ca2+]i predominantly
      via H2 receptors and to a lesser extent via H1 receptors. (ii) The
      agonist/antagonist profile of the H2 receptor-mediated increases in [Ca2+]i
      differs markedly from that for cAMP accumulation, suggesting the involvement of
      different H2 receptor subtypes. (iii) In HL-60 promyelocytes, histamine activates
      nonselective cation channels and induces functional differentiation via H2
      receptors.

PMID- 1381045
TI  - Both enantiomers of 1-aminocyclopentyl-1,3-dicarboxylate are full agonists of
      metabotropic glutamate receptors coupled to phospholipase C.
AB  - We tested the effects of two enantiomers of a glutamate analogue, (trans)-1
      aminocyclopentyl-1,3-dicarboxylate (t-ACPD), in striatal and cerebellar neurons
      in primary culture, as well as in Xenopus oocytes injected with cerebellar rat
      RNA. In the presence of MK-801, to avoid N-methyl-D-aspartate receptor
      activation, and 3 microM tetrodotoxin, both enantiomers [(1R,3S)- and (1S,3R)-t
      ACPD] stimulated inositol phosphate (InsP) formation both in striatal neurons
      after 9-11 days in vitro [EC50, 3.7 +/- 1.1 microM, three experiments, and 33 +/-
      7.5 microM, three experiments; maximal stimulatory effects, 252 +/- 15%, 13
      experiments, and 269 +/- 15% of basal InsP formation, 14 experiments, for (1R,3S)
      and (1S,3R)-t-ACPD, respectively] and in cerebellar granule cells after 9-11
      days in vitro [EC50, 50 +/- 18 microM, four experiments, and 307 +/- 92 microM,
      four experiments; maximal stimulatory effects, 401 +/- 71%, eight experiments,
      and 423 +/- 75% of basal InsP formation, eight experiments, for (1R,3S)- and
      (1S,3R)-t-ACPD, respectively]. These effects were not additive, indicating that
      both enantiomers acted at the same receptor molecule. When we monitored t-ACPD
      induced increases in intracellular Ca2+ concentration ([Ca2+]i) with fura-2 ratio
      imaging, we found that both enantiomers could elicit similar increase in [Ca2+]i,
      in the presence of 1 microM MK-801 and 3 microM tetrodotoxin; these effects were
      also observed in the absence of external Ca2+. Moreover, in Xenopus oocytes
      injected with adult rat cerebellar RNA, both drugs elicited oscillatory increases
      of a Ca(2+)-dependent chloride conductance, with similar efficacy, with (1R,3S)-t
      ACPD being the more potent isomer. These data are in contradiction to previous
      reports showing that, in "immature" cerebellar neurons and adult hippocampal
      slices, (1S,3R)-t-ACPD was either the only active enantiomer or a full agonist of
      metabotropic receptors, with (1R,3S)-t-ACPD being ineffective or a partial
      agonist. However, performing these experiments in immature (2-3 days in vitro)
      striatal or cerebellar neurons, we found that only (1S,3R)-t-ACPD was active in
      stimulating [Ca2+]i.

PMID- 1381046
TI  - Enalapril reduces the enhanced 1,2-diacylglycerol content and RNA synthesis in
      spontaneously hypertensive rat hearts before established hypertension.
AB  - There is evidence that cardiac hypertrophy in spontaneously hypertensive rats
      (SHR) occurs before the development of hypertension. 1,2-Diacylglycerol, which is
      thought to be a second messenger activating protein kinase C, is also produced in
      excess in SHR hearts at 4 weeks of age, before established hypertension. We
      determined myocardial 1,2-diacylglycerol content in SHR with and without prazosin
      and enalapril from 3 to 4 weeks of age. Hearts from untreated SHR had greater RNA
      and DNA synthesis and greater relative weights at 4 weeks of age than those from
      Wistar-Kyoto (WKY) rats. There was no difference in triglyceride content or
      phospholipid species between WKY rats and untreated SHR, except for a higher
      cholesterol content in SHR. Treatment of SHR with enalapril, but not prazosin,
      lowered not only 1,2-diacylglycerol content but also RNA synthesis to the levels
      of WKY rats. Moreover, fatty acids involved in 1,2-diacylglycerol were altered by
      enalapril despite the lack of a difference between WKY rats and untreated SHR.
      Prazosin did not have any effect on 1,2-diacylglycerol fatty acid composition.
      Enalapril may decrease cardiac hypertrophy in SHR by lowering myocardial 1,2
      diacylglycerol production.

PMID- 1381047
TI  - 'Run-off' polymerization with digoxigenin labelled nucleotides creates highly
      sensitive and strand specific DNA hybridization probes: synthesis and
      application.
AB  - In this paper the in vitro synthesis and application of non-radioactively
      labelled strand specific DNA probes is described. The probe is labelled by
      incorporation of nucleotides with the hapten digoxigenin into single-stranded DNA
      during a 'run-off' reaction catalyzed by Thermus aquaticus (Taq) DNA-polymerase.
      The 'run-off' reaction requires a linearized plasmid template and one primer
      binding site at a defined distance from the restriction site. Single-stranded DNA
      can be synthesized during repeated cycles of denaturation, annealing, and
      extension. The conditions for the incorporation of digoxigenin-11-dUTP (dig-11
      dUTP) during polymerization were optimized to generate strand specific DNA
      hybridization probes up to a length of 5000 nt. The strand specificity is
      demonstrated by a dot-blot, with in vitro-transcribed target RNA of c-sis. The
      sensitivity of the probe was tested in a Northern blot, and found to be identical
      to a probe radiolabelled by nick-translation (specific activity 6.5 x 10(8) cpm
      micrograms-1). The resolution of the signals and speed of development was even
      superior compared to the radiolabelled probe.

PMID- 1381048
TI  - The genetic toxicology of cinnamaldehyde.

PMID- 1381049
TI  - Review of the mutagenicity/genotoxicity of butylated hydroxytoluene.
AB  - Butylated hydroxytoluene (BHT) is an effective, widely used, low cost
      antioxidant. A host of studies examining the potential of BHT to cause point
      mutations have been published. They include in vitro studies on various bacterial
      species and strains and on various types of mammalian cell lines as well as in
      vivo studies on Drosophila melanogaster, silk worms and also the mouse specific
      locus test (involving long-term exposure). Together these studies convincingly
      show the absence of a potential for BHT to cause point mutations. A great number
      of studies on many cell types and species have also been carried out to examine
      the potential of BHT to cause chromosome aberrations. In vitro studies have been
      published using plant cells and the WI-38, CHL, CHO, and V79 mammalian cell
      lines. In vivo studies have been carried out on somatic and/or germ cells of
      Drosophila melanogaster, rats and mice. Nearly all studies, especially those
      using validated test systems, indicate that BHT lacks clastogenic potential. In
      vitro studies on bacterial, yeast and various mammalian cell lines including DON,
      CHO, CHL cells and primary hepatocytes demonstrate the absence of interactions
      with or damage to DNA. Taking all the existing data into account, the weight of
      evidence suggests that BHT does not represent a relevant mutagenic/genotoxic risk
      to man.

PMID- 1381050
TI  - Mutagenicity of azo dyes: structure-activity relationships.
AB  - Azo dyes are extensively used in textile, printing, leather, paper making, drug
      and food industries. Following oral exposure, azo dyes are metabolized to
      aromatic amines by intestinal microflora or liver azoreductases. Aromatic amines
      are further metabolized to genotoxic compounds by mammalian microsomal enzymes.
      Many of these aromatic amines are mutagenic in the Ames Salmonella/microsomal
      assay system. The chemical structure of many mutagenic azo dyes was reviewed, and
      we found that the biologically active dyes are mainly limited to those compounds
      containing p-phenylenediamine and benzidine moieties. It was found that for the
      phenylenediamine moiety, methylation or substitution of a nitro group for an
      amino group does not decrease mutagenicity. However, sulfonation, carboxylation,
      deamination, or substitution of an ethyl alcohol or an acetyl group for the
      hydrogen in the amino groups leads to a decrease in the mutagenic activity. For
      the benzidine moiety, methylation, methoxylation, halogenation or substitution of
      an acetyl group for hydrogen in the amino group does not affect mutagenicity, but
      complexation with copper ions diminishes mutagenicity. The mutagenicity of
      benzidine or its derivatives is also decreased when in the form of a
      hydrochloride salt with only one exception. Mutagenicity of azo dyes can,
      therefore, be predicted by these structure-activity relationships.

PMID- 1381051
TI  - Review of the genotoxicity of ozone.
AB  - Ozone is a powerful oxidant, reactive to biomolecules. In aqueous solution it
      decomposes to give hydrogen peroxide, superoxide and hydroxy radicals which can
      take part in secondary reactions. Ozone is a disinfectant that inactivates both
      viruses and bacteria. Although other reactions are primarily responsible for the
      inactivation, cellular DNA is also damaged. Ozone is genotoxic to microorganisms,
      plants and cell cultures in vitro. The results from in vivo cytogenetic studies
      with laboratory animals after inhalation exposure are contradictory. Chromosome
      aberrations in lymphocytes, but not SCEs, have been demonstrated in Chinese
      hamsters but not in mice. Chromatid deletions were induced in pulmonary
      macrophages in rats. No cytogenetic effects have been reported for bone marrow
      cells or spermatocytes. The few experimental and epidemiological studies with
      human subjects do not allow a conclusion on the cytogenetic effects of ozone in
      lymphocytes in humans. No life-long cancer studies have been performed with
      ozone. However, after 4 and 6 months of inhalation exposure, lung adenomas were
      induced in strain A/J mice, but not in Swiss-Webster mice.

PMID- 1381052
TI  - Using the polymerase chain reaction to estimate mutation frequencies and rates in
      human cells.
AB  - The Polymerase Chain Reaction (PCR) has had a significant impact on molecular
      studies of human mutagenesis, mainly in the acceleration of molecular
      characterisation of mutant genes in cells isolated by a phenotypic selection. PCR
      can also be used to study genetic alterations in cells which have not undergone
      phenotypic selection. By modifying the standard PCR parameters, the presence of
      mutations can be assayed in single human cells, creating the potential to
      determine mutation rates in gametes on a cell-by-cell basis (Section I).
      Alternatively, PCR can be used to selectively amplify a mutant gene in a pool of
      normal genomes and thus determine a mutation frequency (Section II). Current
      applications of these two approaches are summarised and critically reviewed.

PMID- 1381053
TI  - Recombinant DNA approaches for the development of metabolic systems used in in
      vitro toxicology.
AB  - In the past few years there has been considerable progress in the development of
      mammalian cell systems for use in genetic toxicology by the stable transfer of
      genes/cDNAs coding for drug metabolizing enzymes directly into the target cell.
      Alternative approaches have also been developed in which mammalian cells are
      transiently transfected with cDNAs coding for drug-metabolizing enzymes and S9
      preparations expressing a single metabolizing enzyme isolated and used for
      metabolic activation. Progress in these areas is reviewed here and the relative
      merits of the different approaches are discussed. Work to date has focused
      primarily on the cytochrome P450 family of enzymes, although other enzyme systems
      involved in xenobiotic metabolism have been used. The central theme of this
      review is the transfer of genetic information to improve the metabolic capability
      of cell systems used in genetic toxicology. However, a basic philosophy of the
      review is that genetic manipulation of cultured mammalian cells has the potential
      for developing systems to be used to better understand chemically induced
      toxicological effects.

PMID- 1381054
TI  - Birth of a normal girl after in vitro fertilization and preimplantation
      diagnostic testing for cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is a common, severe autosomal recessive disease
      caused in a majority of cases by a three-nucleotide deletion (delta F508) in the
      cystic fibrosis transmembrane regulator gene. Current methods of prenatal
      diagnosis involve chorionic-villus sampling or amniocentesis. In vitro
      fertilization and diagnosis during embryonic development before implantation
      would allow only unaffected embryos to be selected for transfer to the uterus,
      thereby avoiding the need to terminate a pregnancy. METHODS: Preimplantation
      diagnosis of cystic fibrosis was attempted in the cases of three couples, both
      members of which carried the delta F508 deletion. In vitro fertilization
      techniques were used to recover oocytes from each woman and fertilize them with
      her husband's sperm. Three days after insemination, embryos in the cleavage stage
      underwent biopsy and removal of one or two cells for DNA amplification and
      analysis. RESULTS: Only two oocytes from one woman were fertilized normally; DNA
      analysis of one of the embryos failed and cystic fibrosis was diagnosed in the
      other (i.e., it was homozygous for delta F508), so neither was transferred. The
      oocytes of each of the other two women produced noncarrier, carrier, and affected
      embryos. Both couples chose to have one noncarrier embryo and one carrier embryo
      transferred. One woman became pregnant and gave birth to a girl free of the
      deletion in both chromosomes. CONCLUSIONS: Preimplantation diagnosis of the delta
      F508 deletion causing cystic fibrosis is possible through in vitro fertilization,
      biopsy of a cleavage-stage embryo, and amplification of DNA from single embryonic
      cells. This approach should be equally applicable to other single-gene diseases
      in which the defect has been identified. Analysis of a series of pregnancies,
      however, will be required to assess the method adequately.

PMID- 1381056
TI  - Vascular endoscopy for intravascular surgery--an experimental study.
AB  - A combination of endoscope and high-pressure saline irrigation system was tested
      in the occlusion of experimental aneurysms, and angioplasty and fibrinolysis of
      vascular occlusive lesions in canine femoral arteries. Endoscopy provided
      detailed information about the aneurysmal orifice and lumen and aided balloon
      placement and detachment. Endoscopy visualized the dynamic changes accompanying
      thrombolysis and the fine intimal injury due to angioplasty invisible on
      angiography. Vascular endoscopy is valuable for pre-, intra-, and postoperative
      evaluation of intravascular interventions.

PMID- 1381055
TI  - Effects of cyclic AMP and butyrate on cell cycle, DNA, RNA, and purine synthesis
      of cultured astrocytes.
AB  - Dibutyryl cyclic monophosphate (dBcAMP) has been shown to inhibit growth, and
      alter the morphology of astrocytes. However, the potential contribution of its
      hydrolytic product, butyrate, in inducing some of the changes that have been
      attributed to dBcAMP, is not clear. DNA, RNA, and purine synthesis were therefore
      studied in primary astrocyte cultures after 24 hours of exposure to varying
      concentrations of butyrate, dBcAMP, and agents that increase intracellular cAMP
      levels. Progression of cells through cell cycle was also studied by flow
      cytometry. Dibutyryl cAMP partially arrested cells in Go/G1 phase of cell cycle
      while sodium butyrate increased the percentage population of cells in G2/M phase.
      DNA synthesis and de novo purine synthesis were inhibited after treatment with
      dBcAMP, sodium butyrate, and various drugs that increase intracellular cAMP
      levels. RNA synthesis was increased with cAMP but was not affected by sodium
      butyrate. Our study shows that at millimolar concentrations, butyrate is capable
      of altering the cell cycle and inhibiting DNA synthesis in primary astrocyte
      cultures, in a manner that is similar although not identical to the effects of
      dBcAMP.

PMID- 1381057
TI  - Effect of radiation therapy against intracranial hemangiopericytoma.
AB  - Seven cases of intracranial hemangiopericytoma were studied retrospectively to
      investigate the efficacy of radiation therapy. Tumor response evaluated by
      computed tomography and magnetic resonance imaging was obvious after 20-30 Gy
      irradiation. The total reduction rate was 80-90% and continued as long as 5-7
      months after treatment. In five patients receiving radiation therapy before
      radical removal, the tumors were easily removed without massive hemorrhage.
      Histological inspection of specimens after irradiation showed a significant
      disappearance of tumor cells. Pyknosis frequently occurred in endothelial cells,
      and proliferating vessels with hyalinoid degeneration were also seen. Reticulin
      fibers between tumor cells were fewer, split, or absent. Preoperative radiation
      therapy is useful in the treatment of hemangiopericytoma involving considerable
      surgical risk. Postoperative radiation therapy should be given even if removal is
      complete.

PMID- 1381058
TI  - New three-dimensional moving field radiation therapy for brain tumors.
AB  - A new modified rotation radiation method called "three-dimensional moving field
      radiation therapy" is described. The new method uses rotation in many planes
      while maintaining the the same isocenter to achieve a good spatial dose
      distribution. This delivers a high dose to tumors and spares the surrounding
      normal structures. This easy method can be carried out using the equipment for
      conventional rotation radiation therapy. The new method was superior to the one
      plane rotation radiation therapy using a physical phantom with film, a chemical
      phantom using the iodine-starch reaction, and a new biological model using tumor
      cells. Treatment of six brain tumors irradiated with total air doses of 50-60 Gy
      caused no hair loss or radiation necrosis.

PMID- 1381059
TI  - "True" posterior communicating artery aneurysm--report of two cases.
AB  - Two cases of true posterior communicating artery (PcomA) aneurysm are described.
      A 27-year-old female with subarachnoid hemorrhage demonstrated a saccular
      aneurysm at the branch of the anterior choroidal artery from the PcomA. The
      aneurysm was successfully clipped. A 23-year-old male involved in an automobile
      accident suffered from traumatic subarachnoid hemorrhage. Computed tomography 10
      weeks after head injury demonstrated a high-density mass in the right parasellar
      region, diagnosed as a traumatic aneurysm arising from the PcomA. The aneurysm
      was successfully clipped. Histological examination demonstrated findings
      consistent with true aneurysm.

PMID- 1381060
TI  - Ruptured cerebral aneurysm associated with coarctation of the aorta--report of
      two cases.
AB  - Two cases of ruptured cerebral aneurysm associated with coarctation of the aorta
      are presented. The aneurysms were successfully clipped in the acute stage prior
      to correction of the coarctation. Ruptured aneurysm should be treated as early as
      possible, and unruptured aneurysm should also be treated before aortic repair, if
      the general condition of the patient allows.

PMID- 1381061
TI  - Lymphocytic adenohypophysitis with sudden onset of diabetes insipidus in
      menopausal female--case report.
AB  - A rare case of a postmenopausal (60-year-old) female with lymphocytic
      adenohypophysitis manifesting as a sudden onset of diabetes insipidus is
      reported. Magnetic resonance imaging with gadolinium-diethylene
      triaminepentaacetic acid enhancement showed a spherical lesion, approximately 1
      cm in diameter, in the sella turcica and a thickened, deviated pituitary stalk.
      The abnormal tissue was totally removed. Histological examination showed marked
      infiltration of lymphocytes and plasma cells. Postoperatively, the pituitary
      stalk became normal. Preoperative differentiation of lymphocytic
      adenohypophysitis from pituitary adenoma is extremely difficult, and biopsy is
      essential.

PMID- 1381062
TI  - Recurrent intracranial germinoma refractory to conventional irradiation:
      effective chemotherapy consisting of cisplatin and etoposide--case report.
AB  - Recurrent intracranial germinoma with multiple spinal metastases occurred in a 16
      year-old male presenting with persistent headache and visual disturbances.
      Computed tomography revealed enhanced lesions in the pineal region, anterior
      horn, and infundibulum. Conventional irradiation achieved remission, but local
      recurrences requiring further irradiation occurred after 23 months. Magnetic
      resonance imaging showed multiple spinal metastases 11 months later. Partial
      removal of the spinal lesions gave a histological diagnosis of typical germinoma.
      Postoperatively, intracranial recurrences were again detected. Chemotherapy
      consisting of intravenous cisplatin and etoposide achieved remission and no
      recurrence has occurred for 12 months.

PMID- 1381063
TI  - Cerebellar astrocytoma with repeated episodes of fourth ventricle isolation
      causing peritoneal shunt tube obstruction--case report.
AB  - A 9-year-old girl underwent total removal of a cerebellar astrocytoma complicated
      by hydrocephalus after postoperative meningitis, requiring a ventriculoperitoneal
      shunt. Five months later, headache, vomiting, and gait disturbance appeared and
      computed tomography detected enlarged fourth ventricle. A fourth
      ventriculoperitoneal shunt resulted in immediate relief of all symptoms. After 2
      months, obstruction of the peritoneal tube required shunt reconstruction. This
      recurred three times in 8 months. At the last operation, tumor cells were
      detected in the cerebrospinal fluid and the substance clogging the tube. This
      suggested that the tumor had recurred and clogging by tumor cells had caused the
      repeated episodes of isolated fourth ventricle. Radiation therapy prevented
      further shunt obstruction and achieved remission of all signs and symptoms.

PMID- 1381065
TI  - Brain tumor registry of Japan.

PMID- 1381064
TI  - Intracavernous epidermoid tumor presenting with abducens nerve paresis--case
      report.
AB  - An unusual case of a pediatric epidermoid tumor entirely located in the cavernous
      sinus is reported. A 6-year-old boy presented with left abducens nerve paresis
      which developed over 2 months. Neuroimaging demonstrated a lesion in the left
      cavernous sinus. Part of the tumor capsule and the pearly contents were removed
      by the left pterional approach through Dolenc's anterolateral triangle. No
      bleeding from the cavernous sinus occurred. The tumor was histologically
      identified as an epidermoid tumor. Postoperatively, the abducens nerve paresis
      improved. The presence of dural reflection in the lateral wall of the cavernous
      sinus and displacement of the intracavernous internal carotid artery are useful
      indicators for intracavernous lesions.

PMID- 1381066
TI  - Dorsal column stimulation induces release of serotonin and substance P in the cat
      dorsal horn.
AB  - The neurohumoral mechanisms behind the pain-suppressing effect of dorsal column
      stimulation (DCS) still remain obscure. Experimental observations have indicated
      an inhibitory role for serotonin and, under certain conditions, also for
      substance P (SP), on nociceptive transmission in the spinal cord. Furthermore,
      some observations suggest that these substances might be involved in the effect
      of DCS. The present series of experiments was undertaken to investigate whether
      serotonin and SP are released in the dorsal horn by DCS. Twenty-one adult cats,
      in some experiments anesthetized, in others decerebrated at the midcollicular
      level, were used. Microdialysis probes were implanted bilaterally in lumbar
      dorsal horns (L5-L7) and perfused with Krebs' solution. Dialysates were analyzed
      for serotonin by high-performance liquid chromatography or for SP by
      radioimmunoassay. DCS was applied at the thoracolumbar junction with current
      parameters similar to those used clinically in humans. DCS induced a significant
      release of serotonin in the dorsal horn of decerebrated animals (173 +/- 83%
      increase; mean +/- standard error; n = 4; P less than 0.01), whereas the levels
      of the metabolite 5-hydroxyindoleacetic acid were not significantly influenced.
      In contrast, no release of SP could be recorded in response to DCS in the
      decerebrated preparation, although peripheral nociceptive stimulation (pinch) and
      noxious electric dorsal root stimulation induced an elevation of the SP levels.
      However, in intact animals DCS provoked a marked SP release in the dorsal horn
      (190 +/- 92% increase; n = 7; P less than 0.01). The release of serotonin and SP
      after DCS may indicate that these substances participate in the mediation of the
      pain alleviating effect of DCS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381067
TI  - Antibodies against Epstein-Barr nuclear antigen (EBNA) in multiple sclerosis CSF,
      and two pentapeptide sequence identities between EBNA and myelin basic protein.
AB  - The Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to
      several disparate malignancies. Prior studies on patients with multiple sclerosis
      (MS) showed that 100% are EBV-seropositive and that their blood contains higher
      antibody titers than those of controls to both transformation and lytic cycle
      antigens. We performed three different assays for antibodies in CSF to three
      major EBV antigens from patients with MS and controls. Among 93 patients with MS,
      79 (85%) had CSF that reacted with a 70 kD protein, shown to be the nuclear
      antigen, EBNA-1, whereas only 11 (13%) of 81 EBV-seropositive controls reacted, p
      less than 0.001. The CSF of all 14 MS patients, unreactive on immunoblots,
      contained oligoclonal bands on agarose electrophoresis. Together, the two
      techniques exhibit 100% sensitivity in the confirmatory diagnosis of MS. We also
      performed amino acid searches of the Protein Identification Resource sequence
      database for protein homologies to EBNA. Two pentapeptide identities were found
      between EBNA-1 and myelin basic protein: QKRPS and PRHRD. None of more than
      32,000 other proteins in the database contained both pentapeptides. In healthy
      EBV-seropositive persons, the EBV-specific, MHC-restricted T lymphocytes keep the
      EBV-containing B lymphocytes locked in the transformed state. However, in the
      host genetically susceptible to MS, the same population of lymphocytes might
      recognize and interact with either of the two identified pentapeptides,
      inadvertently damaging MBP.

PMID- 1381068
TI  - Prostate-specific antigen and the bone scan.

PMID- 1381069
TI  - U.S. Government disseminates acute pain treatment guidelines: will they make a
      difference?

PMID- 1381070
TI  - Follow-up results from a randomised controlled trial evaluating in- and
      outpatient pain management programmes.
AB  - This study reports a 9-18 month follow-up of a randomised controlled trial of
      pain management programmes for chronic, non-malignant pain. Twenty-two
      inpatients, 18 outpatients and 12 control subjects completed the follow-up
      assessments. Significant treatment effects were demonstrated by the inpatient
      group on pain ratings, the Pain Behaviour Checklist, and General Health
      Questionnaire, with similar effects demonstrated by the outpatient group on the
      former 2 measures. The findings were confounded by higher inpatient scores at
      pretreatment, in comparison with the 2 other conditions. There was a high drop
      out rate of subjects, particularly from the control condition which illustrates
      the limitations of controlled group designs in this area. Analgesic use, activity
      levels and pain ratings were also evaluated using the criteria for 'success'
      described by Malec et al. (1981). Results indicated that 68% of inpatients, 61%
      of outpatients and 21% of control subjects met all 3 criteria. Both treatment
      programmes were effective in returning patients to paid employment, whilst 3
      control group patients gave up work. The cost-benefit implications of these
      changes are discussed. We conclude that pain management programmes contribute
      substantially to the rehabilitation of chronic pain sufferers.

PMID- 1381071
TI  - Automated 'pain drawing' analysis by computer-controlled, patient-interactive
      neurological stimulation system.
AB  - We have developed a new method for the collection and analysis of pain drawings,
      as part of a computer-controlled, patient-interactive system for use with
      implanted neurological stimulators. The system has been tested in 44 patients
      with permanently implanted spinal cord stimulators for the relief of chronic,
      intractable pain. Patients interact directly with the system, using a graphics
      tablet, to enter pain drawings and corresponding outlines of their perceptions of
      stimulation paresthesias, for different stimulating pulse parameters and
      electrode geometries. Image analysis software has been developed to examine these
      data quantitatively. This precludes the inter-rater inconsistencies reported for
      manual pain drawing scoring techniques. A highly significant correlation has been
      observed between patients' analog ratings of the overlap of pain by paresthesias
      and the results of our automated analysis of graphic data. This in turn has been
      found to correlate with clinical observations of pain relief. The contemporary
      implantable stimulation devices supported by our system permit non-invasive
      selection of stimulating anodes and cathodes from a linear array of 4 electrodes.
      The 50 possible electrode combinations have certain geometric features, which we
      have entered into a multivariate statistical analysis, to determine their
      relationship with the overlap of pain by paresthesias. One particular
      configuration (cathode(s) flanked by anode(s) above and below) is significantly
      better, by this measure, than all the alternatives. This is consistent with prior
      clinical observations that this configuration is favored by patients whose
      systems have been adjusted by conventional, manual methods. Pain drawing' entry
      and analysis by a computerized, patient-interactive system has been useful in
      this specialized setting and may have broader applications.

PMID- 1381072
TI  - The use of methylphenidate in patients with incident cancer pain receiving
      regular opiates. A preliminary report.
AB  - In this open, uncontrolled trial, 15 patients with severe incident cancer pain
      receiving regular opiates were administered 10 mg oral methylphenidate (MP) at
      08.00 h and 15 mg at 12.00 h in order to antagonize opiate-induced sedation. The
      daily dose of opiate was increased by 30% 24 h after starting MP, followed by a
      10% increase twice a day until maximal tolerated dose. In 14 evaluable patients,
      pain (VAS 0-100 mm), sedation (VAS), and mean equivalent daily dose (MEDD) of
      morphine were 55 +/- 17, 65 +/- 18 and 248 +/- 150 48 h before MP, versus 38 +/-
      12 (P less than 0.01), 42 +/- 12 (P less than 0.01), and 405 +/- 130 (P less than
      0.01) 48 h after MP, respectively. After 48 h of treatment, 12 of 14 patients
      felt better on MP, 2 of 12 patients felt no difference, and no patients felt
      worse (P less than 0.05). We conclude that the addition of MP allowed for an
      increase in the MEDD of morphine and increased pain control. Controlled double
      blind trials should be performed.

PMID- 1381073
TI  - [Ring chromosome 14].

PMID- 1381074
TI  - Pacemaker polarity configuration--what is best for the patient?

PMID- 1381075
TI  - Right atrial diverticulum presenting as Wolff-Parkinson-White syndrome.
AB  - A 7-year-old male presenting with Wolff-Parkinson-White syndrome and tachycardia
      was suspected by echocardiographic and magnetic resonance imaging evaluation to
      have an associated pericardial cyst anterior to the right atrium and ventricle.
      Electrophysiological evaluation demonstrated short antegrade and retrograde
      accessory connection refractory periods, with inducible orthodromic
      atrioventricular reentrant tachycardia. Surgical observation revealed a rare
      congenital right atrial diverticulum bridging the anterior right atrioventricular
      groove, with the functional accessory connection lateralized to the medial aspect
      of this structure. Endocardial and epicardial incisions and cryolesions placed
      along the anterior right atrioventricular groove initially appeared successful,
      but preexcitation recurred within 4 weeks postoperatively.

PMID- 1381076
TI  - Coronary air embolism complicating transseptal radiofrequency ablation of left
      free-wall accessory pathways.
AB  - Radiofrequency catheter ablation is an important new technique for curing
      patients with accessory pathway-mediated tachycardia. Ablation of left free-wall
      accessory pathways may be accomplished either by a retrograde, transarterial
      approach or via a transseptal approach using a long vascular sheath. We describe
      air embolization into the coronary artery as a complication of the transseptal
      approach, which was temporally associated with catheter exchange. While there
      were no permanent adverse sequelae, this report emphasizes the need for
      scrupulous attention to the possible insinuation of air during procedures
      involving long vascular sheaths across the atrial septum. To prevent air
      embolism, we recommend slow removal of the ablation catheter along with
      continuous flushing with heparinized saline during exchanges.

PMID- 1381077
TI  - Does dual chamber or atrial pacing prevent atrial fibrillation? The need for a
      randomized controlled trial.
AB  - Partially due to recent reports that cardiac antiarrhythmic therapy may have
      adverse effects on patient survival, clinicians have become more interested in
      the nonpharmacological prevention of atrial fibrillation. There is a large body
      of literature that suggests that the rate of development of atrial fibrillation
      in paced sick sinus syndrome patients is much lower in those patients who have
      received an atrial-based system, rather than a VVI system. However, all the
      published studies to date are retrospective, and fraught with potential bias
      favoring the AAI or DDD group. The authors strongly believe that the only way to
      determine if these suggestive but uncertain retrospective analyses are correct is
      to apply the same scientific rigor to this problem as has been applied to many
      other problems in cardiovascular medicine and perform a prospective randomized
      trial. A proposed trial design is discussed.

PMID- 1381078
TI  - Significance of ventricular pacing site in manifest entrainment during
      orthodromic atrioventricular reentrant tachycardia with left-sided accessory
      pathway.
AB  - We examined entrainment by ventricular pacing in six patients during orthodromic
      atrioventricular reentrant tachycardia (AVRT) utilizing a left-sided lateral
      accessory pathway. Constant fusion and progressive fusion were demonstrated in
      all patients by left ventricular pacing during tachycardia, but in none of the
      patients by right ventricular pacing. When left ventricular pacing was performed
      during AVRT, the antidromic wave front from the pacing impulse (n) collided with
      the orthodromic wave front of the previous pacing beat (n - 1) within the
      ventricle, therefore, constant fusion and progressive fusion were demonstrated in
      the surface electrocardiographic QRS complexes. On the other hand, when right
      ventricular pacing was performed during orthodromic AVRT, the antidromic wave
      front from the pacing impulse (n) collided with the orthodromic wave front of the
      previous paced beat (n - 1) within the normal atrioventricular pathway, and
      constant fusion and progressive fusion were therefore not demonstrated. These
      phenomena were explained by the relationship of the ventricular pacing site and
      the reentrant circuit. This study demonstrates the importance of the pacing site
      in manifest entrainment of orthodromic AVRT during ventricular pacing.

PMID- 1381079
TI  - Radiofrequency ablation of accessory pathways: characteristics of transiently and
      permanently effective pulses.
AB  - The purpose of this study was to characterize and compare the radiofrequency
      current applications that produced permanent or transient accessory pathway
      conduction block. One hundred fifty-two radiofrequency energy applications that
      induced permanent (permanently effective pulses, n = 48) or transient
      (transiently effective pulses, n = 104) accessory pathway block in 57 patients
      with 60 accessory pathways were analyzed. The time from the onset of current
      application to disappearance of preexcitation or termination of supraventricular
      tachycardia by permanently effective pulses was 1-15 seconds (mean 3.6 +/- 3.8
      sec) compared to 2-29 seconds (mean 11.5 +/- 7.5 sec) by transiently effective
      pulses (P less than 0.01). After transiently effective pulses that induced block
      in accessory pathway, conduction resumed within 5 minutes while induced block by
      permanently effective pulses persisted in 44 of 48 patients (92%) during follow
      up of 11 +/- 12 months. The accessory pathway conduction returned in the
      remaining four patients after ablation 2 weeks to 7 months. After transiently
      effective pulses, 41 impulses were delivered to the same site using a higher
      power output (n = 32) and/or longer energy delivery duration (n = 20) without new
      mapping of accessory pathway location. Thirty-six of these impulses again
      resulted in transient accessory pathway block, four had no effect, only one
      impulse induced a permanent block in the accessory pathway. Pulses with higher
      power outputs tended to induce transient effects more frequently than pulses with
      lower energy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381080
TI  - Driving restrictions advised by midwestern cardiologists implanting cardioverter
      defibrillators: present practices, criteria utilized, and compatibility with
      existing state laws.
AB  - Although some patients remain at risk of losing physical control or collapsing
      after implantation of a cardioverter defibrillator for sustained ventricular
      arrhythmias, little is known about restrictions advised by arrhythmia specialists
      to patients with implanted devices concerning physical activities such as
      driving. In this study, all of the 58 cardiologists implanting cardioverter
      defibrillators in three contiguous midwestern states were surveyed to determine
      present practices and the compatibility of these practices with existing state
      law. Of the 51 respondents (88%), 27 cardiologists (53%) advised only those
      implanted patients who had had arrhythmia-induced presyncope or physical collapse
      to cease driving. Twenty two of the remaining cardiologists (43%) advised all
      implanted patients to cease driving, whereas two cardiologists (4%) never advised
      any implanted patient to restrict driving. Permanent driving abstinence was
      advised by seven of the responding cardiologists (14%), while temporary driving
      abstinence for periods of 2-12 months (mean 6 +/- 3 months) was recommended by
      the remaining 42 respondents (82%) who advised against driving. The criteria
      utilized, driving restrictions advised, and durations advised for driving
      restrictions were not uniform in any of the 13 surveyed university and
      nonaffiliated cardiology practices with greater than or equal to 2 implanting
      cardiologists. Overall, 38 cardiologists (74%) advised against driving and
      recommended durations that equaled or exceed their state's minimum legal
      requirements, although only 27 of the 51 cardiologists (53%) based their practice
      upon knowledge of their state's driving laws. The results of this survey suggest
      that the majority of cardiologists who implant cardioverter defibrillators advise
      their patients against driving postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381081
TI  - Direct current application: easy induction of ventricular fibrillation for the
      determination of the defibrillation threshold in patients with implantable
      cardioverter defibrillators.
AB  - For the determination of the defibrillation threshold, the induction of
      ventricular fibrillation is mandatory. However, in severely damaged hearts it is
      sometimes difficult to induce ventricular fibrillation by rapid stimulation or
      alternating current. Only rapid nonclinical ventricular tachycardias may result,
      and their cardioversion threshold may be different from the defibrillation
      threshold. Therefore, it was the purpose of this study to test the potential of
      direct current (DC) application to rapidly induce ventricular fibrillation in
      patients with an implanted cardioverter defibrillator. The defibrillation
      threshold had to be determined in 13 patients (9 with coronary heart disease, 4
      with dilative cardiomyopathy, ejection fraction 35%) during and 2 weeks after the
      implantation of a cardioverter defibrillator. DC was applied 37 times by a
      commercially available 9-V DC battery via a bipolar catheter for about 3 seconds.
      Ventricular fibrillation was induced 23 times (62%) and rapid nonclinical
      ventricular tachycardias were induced six times (16%). In one patient clinical
      ventricular tachycardia was observed. In seven instances (19%) sinus rhythm
      remained. In 12 of the 13 patients, ventricular fibrillation could be induced by
      DC. Thus, the induction of ventricular fibrillation by DC application may serve
      as an additional tool to induce ventricular fibrillation, determining the
      defibrillation threshold in implantable cardioverter defibrillator patients.

PMID- 1381082
TI  - Transtelephonic interrogation of the implantable cardioverter defibrillator.
AB  - Third generation implantable cardioverter defibrillators (ICDs) have extensive
      memory capability to store data about the patient's arrhythmias and the effect of
      therapies delivered by the ICD. However, this data has so far been accessible
      only when the patient attends the pacing clinic. Two Medtronic 9421 PCD
      TeletraceR transmitters have been used to interrogate Medtronic 7216A and 7217B
      PCD S at distances of up to 300 miles from our hospital and transmit the data to
      a 9420 PCD TeletraceR receiver. Successful transmission of data has been obtained
      on 50 occasions with 100% data concordance with repeat transmission. The system
      can reduce the number of unscheduled clinic visits, reduce delay in making a
      diagnosis following unexpected delivery of a shock therapy, and reassure patients
      about to be discharged following ICD implantation. The benefits are magnified
      where patients reside far away from the implanting center.

PMID- 1381083
TI  - Improved chronic epicardial pacing in children: steroid contribution to porous
      platinized electrodes.
AB  - Although new "low threshold" epicardial electrodes combine steroid with a porous,
      platinized-platinum surface, the actual contribution of steroid elution has not
      been established. We evaluated this new electrode surface design with and without
      steroid in 13 children, ages 1-22 years. Both electrodes are unipolar and of
      similar surface area. The Medtronic Model 4951-P is a barb design for
      epimyocardial insertion without steroid while the Model 10295A is a steroid
      eluting, epicardial disk-shaped design. Both electrodes were implanted for atrial
      and ventricular pacing. At implant, sensed P and R waves, and pacing impedances
      were comparable between both electrodes. There were no significant differences
      between initial measured pulse width or calculated energy thresholds for the
      first 2 months following implant. Strength-duration curves for both electrodes at
      1 month were comparable to implant values. After 2 months, the threshold of the
      nonsteroid electrode peaked and stabilized at a significantly higher (P less than
      0.05) level than the more constant steroid eluting electrode. This difference
      continued for the first year following implant. We conclude that the new porous,
      platinized-platinum electrode design intrinsically limits initial electrode
      tissue interface reactivity in children and improves epicardial pacing with low
      chronic threshold values. Steroid elution augments these intrinsic qualities by
      maintaining fibrous capsule stability with more constant low thresholds over
      time.

PMID- 1381084
TI  - Comparison of isoproterenol and exercise tests in asymptomatic subjects with
      Wolff-Parkinson-White syndrome.
AB  - In order to evaluate the effects of increases of sympathetic tone in ventricular
      response during atrial fibrillation and in the relationship between the accessory
      pathway effective refractory period (ERP) and ventricular rate during atrial
      fibrillation, 20 male subjects, aged 19 +/- 6 years, were studied
      electrophysiologically in basal conditions, after isoproterenol infusion (2-4
      micrograms/min) and during submaximal bicycle exercise test, at a constant
      workload equal to that which increases the sinus rate to the same extent (140
      beats/min) induced by isoproterenol infusion. Accessory pathway ERP was evaluated
      at the same driven rate (150 beats/min) in both instances. In the control study
      as during both tests atrial fibrillation paroxysms were induced by burst
      stimulation. In control conditions the rate increase from 100 to 150 beats/min
      induced a reduction of accessory pathway ERP from 266 +/- 27 msec to 244 +/- 22
      msec (P less than 0.005). At the same driven rate of 150 beats/min, isoproterenol
      infusion and exercise test induced a more marked shortening of accessory pathway
      ERP to 211 +/- 28 msec (P less than 0.005) and to 214 +/- 29 msec (P less than
      0.005), respectively. Atrial fibrillation paroxysms lasting more than 10 seconds
      were induced in 20/20 cases in the control study, in 15/20 during isoproterenol
      infusion and in 13/19 cases during exercise test. The shortest cycle length
      during atrial fibrillation was reduced from a basal value of 253 +/- 72 msec to
      204 +/- 27 msec (P less than 0.05) during isoproterenol infusion and to 236 +/-
      32 msec (NS) during exercise test.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381085
TI  - Ablation of ventricular tachycardia using multiple sequential transcatheter
      application of radiofrequency energy.
AB  - Multiple sequential radiofrequency energy was applied in the left and right
      ventricles of 24 dogs to produce large ablated areas limited to endocardial and
      subendocardial regions. Endocardial ablation was performed in nine dogs with
      normal ventricles and 15 that had survived remote myocardial infarcts, three with
      inducible sustained monomorphic ventricular tachycardia. A quadripolar catheter
      was positioned either at the site of earliest ventricular activation during
      induced monomorphic ventricular tachycardia or at circumscribed areas of the left
      ventricle. Radiofrequency energy was delivered between two adjacent poles of the
      catheter, successively applying radiofrequency energy to the distal, middle, and
      proximal electrode pairs; this was repeated 9 to 11 times with the catheter in a
      slightly different position. A cumulative energy of 9,688 +/- 4,191 joules
      resulted in an ablated endocardial/subendocardial surface area of 4.7 +/- 2.2 cm2
      (range 2.4-10 cm2, maximum depth 4 mm). Sustained tachycardia was not inducible
      by aggressive programmed ventricular stimulation in the dogs with previously
      inducible tachycardia, indicating successful ablation of the tachycardia foci.
      Only seven normal dogs were available for electrophysiological studies; three
      were used in acute and four in chronic studies. Ventricular tachycardia was not
      induced in the remaining dogs either before or after radiofrequency ablation,
      indicating the lack of an arrhythmogenic effect of this method. Histologic
      examination was performed in all nine normal dogs (five were sacrificed for acute
      pathological examination) as well as in the 15 with myocardial infarction. The
      late pathological examination of the radiofrequency lesion in these 19 animals
      showed homogeneous areas of coagulation necrosis and endocardial proliferation.
      Thus, this modified technique of radiofrequency ablation produced large
      homogeneous endocardial/subendocardial scars suitable for treating ventricular
      tachycardia and showed no evidence of an arrhythmogenic influence.

PMID- 1381086
TI  - The range of sensors and algorithms used in rate adaptive cardiac pacing.
AB  - Implantable sensors play an important role in physiological cardiac pacing.
      Sensors can be classified according to the technical methods in which sensing is
      achieved: the sensing of the evoked ventricular response, intrathoracic impedance
      and body acceleration forces, and the incorporation of special sensors on pacing
      electrodes. These sensors differ in their relative merits in terms of speed,
      proportionality, sensitivity, and specificity of rate response. The efficacy of a
      sensor can be significantly modified by the algorithm used in relating sensor
      signal to a pacing rate change. The currently available types of sensors and
      algorithms are summarized and compared in this review article. The relative
      merits of these sensors and algorithms form the basis for designing a multisensor
      pacing system.

PMID- 1381087
TI  - How a computer computes? Hardware and software based pacemakers.

PMID- 1381088
TI  - A case of cardiac foreign bodies associated with four types of tachycardias.
AB  - A case of cardiac foreign bodies leading to development of four varieties of
      automatic tachycardia is reported. A 51-year-old male with aortic regurgitation
      was admitted to our hospital because of palpitations. An electrocardiogram
      revealed junctional tachycardia with or without left bundle branch block, and two
      types of fascicular tachycardias. Computed tomography showed metallic foreign
      bodies from a fractured guidewire in the membranous portion of the
      interventricular septum, which was inadvertently retained when he underwent
      diagnostic cardiac catheterization at the age of 27.

PMID- 1381089
TI  - Late development of conduction block over the Mahaim fibers after electrical
      atrioventricular junction ablation for Mahaim fiber tachycardia.

PMID- 1381090
TI  - Activity-based pacing: comparison of a device using an accelerometer versus a
      piezoelectric crystal.

PMID- 1381091
TI  - Blood culture results as determinants in the organism identification of bacterial
      meningitis.
AB  - The diagnosis of bacterial meningitis depends on a lumbar puncture (LP).
      Sometimes, antibiotics are administered before a LP that is delayed owing to
      prior need for computerized tomography (CT) scan, technical problems, inability
      to obtain consent, or an unstable patient. We examined the accuracy of blood
      culture, cerebrospinal fluid (CSF) Gram's stain, and antigen detection by latex
      for organism identification of meningitis. All patients admitted to the
      Children's Hospital of Buffalo between January 1, 1984 and December 31, 1989 and
      having a CSF culture diagnosis of bacterial meningitis had their charts
      retrospectively reviewed. Patients excluded from the study were those with neural
      tube defects or CSF catheters, those admitted directly to the Intensive Care
      Nursery (ICN), those whose positive CSF cultures were determined to be a
      contaminant, those whose medical records were not found, or those older than 16
      years. We analyzed a total of 178 patients with positive CSF cultures and the
      confirmed diagnosis of bacterial meningitis. Of 169 patients who had a blood
      culture performed, 86% had the organism responsible for meningitis recovered by
      this test, with the highest yield of 91% occurring in the 2.5-month to 24-month
      age group. Blood culture identified the bacteria in 94% of those patients with
      Haemophilus influenzae meningitis, and this yield increased to 100% when patients
      who had been pretreated with antibiotics were excluded. The combination of blood
      culture, CSF Gram's stain, and/or latex agglutination identified the causative
      bacteria in 92% of patients with meningitis. Blood culture, CSF Gram's stain, and
      latex agglutination are useful in identifying the organism causing pediatric
      meningitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381093
TI  - Aneuploidy indices in biochemical screening.

PMID- 1381092
TI  - Evidence for a relationship between recovery from anaesthesia, modified state of
      consciousness and striatal voltammetric levels of ascorbic acid.
AB  - The effects of various procedures which modify consciousness were studied on the
      extracellular concentration of ascorbic acid (AA), 3,4-dihydroxyphenylacetic acid
      (DOPAC) and 5-hydroxyindolacetic acid (5HIAA) in rat striatum, as measured by
      differential pulse voltammetry (DPV) with electrically pretreated carbon fibre
      micro-electrodes (CFE). Recovery from anaesthesia (produced by 500 mg/kg i.p.
      chloral hydrate) was accompanied by a six-fold increase in extracellular striatal
      AA levels, while negligible changes in DOPAC and 5HIAA occurred. Following
      complete recovery from anaesthesia, the animals were re-injected with the same
      dose of anaesthetic which specifically reduced AA levels by 90% (DOPAC levels
      were unchanged and 5HIAA concentrations slightly reduced). In conscious rats, the
      neuroleptic haloperidol (1 mg/kg i.p., n = 5) and the minor tranquillizer
      diazepam (10 mg/kg i.p., n = 5), both considered as behaviourally depressant
      drugs, reduced extracellular AA levels to 50% of controls. The psychomotor
      stimulant D-amphetamine (1 mg/kg i.p., n = 5) increased AA levels by 90% over
      controls. Stress activation of animals (handling for 10 min, n = 10) also
      produced a transient, significant increase (180% of control values) in this
      striatal parameter. Taken together with previous reports, our results suggest a
      close relationship between the state of consciousness and extracellular AA levels
      in the rat striatum and that this relationship appears to be more correlated to
      AA as no such clear interdependence was noted between the levels of consciousness
      and extracellular striatal DOPAC or 5HIAA.

PMID- 1381094
TI  - [Determining the time of diabetes mellitus onset by the level of glycosylated
      keratin in hair].
AB  - The levels of glycosylated hemoglobin (HbA1c) and glycosylated keratin were
      studied along the hair length in 17 patients with newly detected insulin
      dependent diabetes mellitus (IDDM) aged 7 to 33, in 14 patients with newly
      detected noninsulin dependent diabetes mellitus (NIDDM) aged 46 to 73, and in 41
      healthy subjects. The level of glycosylated keratin in healthy hairs along the
      entire length varied within 0.094-0.124 mumol of fructosamine per 100 mg of hair.
      In 10 of 17 patients of the IDDM group measurements of glycosylated keratin
      levels made it possible to determine the time of appearance of diabetes mellitus,
      in 13 patients of the NIDDM group these levels along the entire hair length were
      elevated. The determination of these levels permitted the estimation of the time
      of appearance of IDDM. Its manifestation followed a long period (1-2 yrs.) of
      latent derangements of carbohydrate metabolism. In NIDDM patients the time of
      appearance of disease is difficult to determine because of the limited hair
      length and a long latent period of disease (over 2-3 yrs.).

PMID- 1381096
TI  - Trophic effects of unsulfated cholecystokinin on mouse pancreas and human
      pancreatic cancer.
AB  - The effect of unsulfated cholecystokinin on pancreatic growth was evaluated in
      two experimental models in vivo and in vitro. Mice were injected with sulfated
      cholecystokinin (CCKs) or unsulfated cholecystokinin (CCKu) (10 or 20
      micrograms/kg) or vehicle twice daily for 15 days. Animals were then killed and
      pancreatic weights, protein, amylase, and DNA content were evaluated. In vitro,
      growth was evaluated by DNA synthesis and viable cell counts. MIA PaCa-2 and BxPC
      3 human pancreatic cancer cells were treated with CCKs or CCKu (10(-12) to 10(-9)
      M) for 48 or 72 h in the presence of [3H]thymidine to evaluate DNA synthesis.
      Viable cell counts were performed on both cell lines grown in the presence or
      absence of unsulfated CCK (10(-12) to 10(-9) M) for 96 h. Pancreatic weight,
      protein, amylase, and DNA were significantly increased in animals treated with
      either CCKs or CCKu. However, pancreatic weight, protein, and amylase were
      significantly higher in mice treated with CCKs compared to CCKu (p less than
      0.005). DNA content and index of hyperplasia were the same whether mice were
      treated with CCKs or CCKu. CCKu was as potent a stimulus for DNA synthesis as
      CCKs in MIA PaCa-2 and BxPC-3 cells. Finally, CCKu increased cell counts in both
      pancreatic cancer cell lines. These data suggest that the mechanisms responsible
      for CCK-induced growth of normal pancreas and pancreatic cancer may differ from
      those that regulate secretion.

PMID- 1381095
TI  - Endogenous cholecystokinin, the major factor responsible for dietary protein
      induced pancreatic growth.
AB  - This study was undertaken to clarify the role of endogenous cholecystokinin (CCK)
      in induction of pancreatic growth stimulated by a high protein diet. Rats with
      i.v. jugular cannulae in place and kept in Bollman cages were adapted to 5%
      casein diet for 9 days and switched to 70% casein for 2 days. MK-329, a CCK
      receptor antagonist, and SMS 201-995, a somatostatin agonist, were continuously
      infused at 0.5 mg/kg/h and 5 micrograms/kg/h, respectively, starting at the onset
      of feeding 70% casein. The 5 and 70% casein control groups were infused with
      saline. Feeding 70% casein significantly stimulated pancreatic hyperplasia and
      tissue hypertrophy. MK-329 and SMS 201-995 totally prevented 70% casein-induced
      increases in pancreatic weight and total RNA and DNA contents. The results
      indicate that endogenous CCK is the major factor responsible for pancreatic
      growth induced by a high protein diet.

PMID- 1381097
TI  - Effects of stress on the development of chronic pancreatitis.
AB  - In this study, the effects of chronic water immersion stress on the pancreas were
      investigated in four groups of rats (each group, n = 9): stress + cerulein group,
      stress group, cerulein group, and control group. Stress + cerulein rats were
      treated with water immersion stress for 5 h and two intraperitoneal injections of
      20 micrograms/kg body wt of cerulein once a week for 16 weeks. In the macroscopic
      findings of the pancreas, all rats in the stress+cerulein group exhibited
      moderate or distinctive congestion of blood vessels, gland atrophy, and fatty
      changes, while some of them showed bleeding. Microscopically, they all exhibited
      moderate or severe fibrosis, inflammatory cell infiltration, fatty changes,
      destruction of lobular architecture, and hemosiderin deposits, while some of them
      also showed bleeding. The stress group without treatment with cerulein injections
      showed slight fibrosis, hemosiderin deposits, and bleeding. The cerulein group
      without stress treatment showed fatty changes, but no inflammatory cell
      infiltration or fibrosis. In the stress + cerulein group only, the contents of
      digestive enzymes and protein in the pancreas were approximately 55% lower than
      those of the control group, whereas those in other groups did not show
      significant reduction. These findings suggest that stress plays some role in the
      development of chronic pancreatitis, perhaps by causing circulatory disturbance
      and blood vessel injury.

PMID- 1381098
TI  - Carbonic anhydrase II gene expression in mouse pancreatic duct cells.
AB  - Our goal is to create a transgenic mouse model for human pancreatic duct cell
      adenocarcinoma using the promoter/enhancer region of the carbonic anhydrase (CA)
      II gene to drive the expression of SV-40 T-antigen in pancreatic duct cells. This
      requires that the CA II gene be expressed in mouse pancreatic duct cells and not
      in other pancreatic cells, as has already been shown to be the case in the human
      and guinea pig pancreas. We have shown with an enzyme histochemical assay that
      mouse pancreatic duct cells contain CA activity in both intact pancreas and
      cultured interlobular duct epithelium. In addition, CA activity was detected with
      a biochemical assay in homogenates of cultured duct epithelium. The specific
      activity of duct cells was 2.75-fold greater than in whole pancreas, suggesting
      that a substantial amount of total pancreatic CA activity is contributed by duct
      cells. At least some of the CA in cultured duct cells was inferred to be CA II by
      Northern blot analysis of RNA extracted from the cells. The concentration of CA
      II mRNA in the cultured duct cells was substantially greater than in whole
      pancreas and would appear to account for the majority, if not all, of the CA II
      in the mouse pancreas.

PMID- 1381099
TI  - Central monoaminergic changes induced by morphine in hypoalgesic and hyperalgesic
      strains of domestic fowl.
AB  - The present research examined morphine dose-response effects on both the formalin
      test and on CNS monoamine (MA) levels and the metabolites dihydroxyphenylacetic
      acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in hypoalgesic (76) and
      hyperalgesic (SN) strains of domestic fowl. Morphine produced a significant
      hypoalgesic response in the 76 strain at 15-45 mg/kg and a significant
      hyperalgesic response in the SN strain at 5-10 mg/kg. In subsequent experiments,
      analyses of whole brain (minus tectum), brainstem, and spinal cord MA, DOPAC, and
      5-HIAA via high-performance liquid chromatography with electrochemical detection
      (HPLC-EC) were performed following morphine administration in both the 76 and SN
      strains. Morphine produced a significant elevation of brain dopamine (DA) and a
      significant elevation of brain, brainstem, and spinal cord serotonin (5-HT) in
      both the 76 and SN strains. Morphine elevated brain norepinephrine (NE) in the 76
      strain. However, morphine failed to affect brain NE in the SN strain. This
      distinct morphine effect on brain NE differentiates strain-dependent hypoalgesia
      and hyperalgesia in domestic fowl.

PMID- 1381100
TI  - Rapid histochemical identification of motor and sensory fascicles: preparation of
      solutions.
AB  - We report a rapid and inexpensive staining method for identification of motor and
      sensory fibers within 1 hour (intraoperatively). This method should be easy to
      use in any hospital where frozen histologic sectioning is available.

PMID- 1381101
TI  - Treatment of the stuck slide.

PMID- 1381102
TI  - Risperidone: clinical safety and efficacy in schizophrenia.
AB  - Risperidone represents a unique pharmacology of potent antagonism of both
      serotonin and dopamine receptors. In a randomized, parallel-group, double-blind
      trial of risperidone vs. haloperidol and placebo in 36 schizophrenic patients in
      acute exacerbation, risperidone showed a quicker onset of antipsychotic activity
      than did haloperidol. Risperidone treatment was statistically superior to
      placebo, with a trend toward superiority to haloperidol. Risperidone did not
      differ from placebo on assessment scales of extrapyramidal side effects, but
      produced significantly less than did haloperidol. There were no major adverse
      reactions associated with risperidone use, but it was noted to reduce the signs
      of tardive dyskinesia. This study suggests that risperidone may offer a superior
      side-effect profile, and possibly greater efficacy, than a standard neuroleptic
      such as haloperidol.

PMID- 1381103
TI  - Neurotransmitter changes in early- and late-onset Alzheimer-type dementia.
AB  - Neurotransmitter-related markers were examined in Alzheimer-type dementia (ATD)
      and studied whether or not there is biochemical difference between the early- and
      late-onset sub-groups. Postmortem brains were obtained from neuropathologically
      diagnosed ATD patients and control subjects with no clinico-neuropathological
      findings indicative of neuropsychiatric diseases. Neurochemical data in the early
      and late-onset groups were compared to the age-matched younger and older control
      groups, respectively, and expressed as a percentage of the mean value in the
      respective controls. Choline acetyltransferase activity and concentrations of
      serotonin and noradrenaline were more severely depleted in the early-onset ATD
      group than in the late-onset ATD group. These findings indicative of
      heterogeneity of ATD patients were discussed from the pathogenetic and
      therapeutic viewpoints.

PMID- 1381104
TI  - Modulation of NMDA receptors by ACh in the central nervous system.
AB  - The effect of acetylcholine (ACh) on N-methyl-D-aspartate (NMDA)-induced
      responses in neurons acutely dissociated from the rat nucleus basalis of Meynert
      (nBM) was investigated with a conventional patch-clamp technique. The whole-cell
      recording revealed that NMDA-induced inward current (INMDA) consisted of
      transient peak and successive steady-state components. With outside-out
      recording, these components were shown to have the identical single channel
      conductance. Pretreating the nBM neurons with the low concentration of ACh
      suppressed the peak component of INMDA, whereas the high concentration
      potentiated it. The modulatory action of ACh was observed in nBM neurons
      dissociated from mature rats. The action was deficient, however, in those from
      immature animals. These results suggest that ACh is either an inhibitory or an
      excitatory modulator of glutamatergic transmission in the central nervous system.

PMID- 1381105
TI  - [The clumsy child].

PMID- 1381106
TI  - Subcellular localization of transferrin and pyrophosphate in liver cells after
      perfusion in situ or incubation in vitro.
AB  - Rat livers were perfused in situ with [125I]-transferrin, FITC-dextran and [32P]
      inorganic pyrophosphate (PP). In a parallel set of experiments rat liver
      homogenates was incubated with [125I]-transferrin and [32P]-PPi. In both sets of
      experiments cellular organelles were prepared by density gradient centrifugation
      in metrizamide. In the perfusion experiments [125I]-transferrin and FITC-dextran
      accumulated in fractions rich in plasma membrane enzymes, whereas in the
      homogenate experiments [125I]-transferrin remained in soluble fractions. [32P]
      PPi remained in soluble fractions in both sets of experiments, i.e. PPi did not
      co-localize with transferrin taken up by intact cells. In another set of
      experiments fractions rich in endosomes were tested for their ability to
      synthesize PPi from ATP. No PPi was found. The results argue against a role for
      PPi in transferrin-iron release within endosomes.

PMID- 1381107
TI  - Serum, disc and egg ELISA for the serodiagnosis of Salmonella gallinarum and S.
      enteritidis infections in chickens.
AB  - An ELISA was evaluated for the serodiagnosis of fowl typhoid and paratyphoid due
      to Salmonella enteritidis in chickens. The hot phenol: water lipopolysaccharide
      (LPS) extract of Salmonella was used as the antigen. Chicken serum, eggs and
      discs impregnated with chicken blood were tested for the presence of antibodies
      against Salmonella factor 'O' 9 antigen. The substrate and chromogen used were
      hydrogen peroxide and orthophenylenediamine respectively. Serological results
      from the experimentally and naturally infected chickens showed close agreement
      between the conventional Serum Tube Agglutination Test (SAT) and serum ELISA
      while serum ELISA results were in close agreement with the egg and disc ELISA
      results. It was noted that ELISA was highly sensitive, convenient and versatile.
      It is concluded that ELISA, especially disc ELISA, ought to replace SAT for
      seroscreening chickens against S. gallinarum and other Salmonella Group D
      infections.

PMID- 1381109
TI  - Production, immunoanalysis and selection of monoclonal antibodies for studies of
      polymorphism of bovine MHC class I antigens.
AB  - Two monoclonal antibodies (MoAbs) were raised against bovine lymphocyte antigens
      of the major histocompatibility complex (MHC) for studies of the polymorphism of
      MHC class I antigens of African cattle. Immunoanalysis of lymphoid tissues and
      molecular weight data were used to characterize the epitopes seen by the MoAbs.
      Competitive binding assays indicated specificity of the MoAbs for two distinct
      epitopes. Application of the MoAbs for MHC typing of a cattle population showed
      that the epitopes were co-expressed on the target MHC antigen but occurred
      independently on non-target MHC antigens. It is concluded that, to obtain MoAbs
      for studies of MHC polymorphism, it is important to conduct large-scale analysis
      using immunoassays and population studies.

PMID- 1381108
TI  - Enhanced spontaneous and induced LAK function in baboons receiving total lymphoid
      irradiation (TLI).
AB  - TLI has potent immunosuppressive effects, but there is concern over its possible
      carcinogenic properties. The aim of the study was to assess to what degree TLI
      may compromise natural killer (NK) and lymphokine activated killer (LAK) cell
      function. There was a significant increase (P less than 0.0001) in both NK-cell
      function (measured against K562 targets) and spontaneous LAK-cell function
      (measured against DAUDI targets) in fresh blood lymphocytes throughout a course
      of 8 x 100 cGy fractionated TLI. This may be related to a three- and sevenfold
      increase, respectively, in CD16+ CD8- and CD56+ CD2- cell frequencies over the
      same period. Mitogen-induced interleukin 2 (IL-2) synthesis from blood
      lymphocytes was inhibited by up to 75% with as little as 100 cGy of TLI.
      Expression of IL-2 receptors on fresh lymphocytes did not vary and remained low.
      Therefore spontaneous LAK occurrence appeared to be triggered through an IL-2
      independent pathway. The in vitro addition of IL-2 verified that cells retained
      their ability to respond to this lymphokine resulting in greatly enhanced induced
      LAK function. This was most probably mediated by CD56+ cells which were found to
      readily express IL-2 receptors upon mitogen stimulation. In conclusion,
      fractionated low-dose TLI appears to enhance MHC unrestricted immune surveillance
      in a manner independent of IL-2 production.

PMID- 1381110
TI  - Development of a malaria T-cell vaccine for blood stage immunity.
AB  - We have defined a strategy for the development of a T-cell vaccine for blood
      stage immunity, taking into consideration the central role of T cells and MHC
      restriction in malaria immune responses. We have used the AMPHI computer
      algorithm to identify putative T-cell epitopes from conserved regions of 11
      Plasmodium falciparum asexual stage proteins. Ten of the eleven proteins are
      currently candidates for vaccine development. Using this algorithm we selected 22
      putative T-cell epitope peptides and 8 control peptides. These peptides were used
      to test the T-cell responses of three defined populations of Caucasians who have
      (1) recovered from P. falciparum malaria, (2) been exposed, but never clinically
      infected, (3) never been exposed or infected. Preliminary analysis of our data
      shows population differences in T-cell responses to putative T-cell epitope
      peptides. Ultimately, these studies will help to identify those T epitopes that
      can be incorporated into a T-cell vaccine for protective immunity.

PMID- 1381111
TI  - Hypoxemia and increased fetal hemoglobin synthesis during the perinatal period.

PMID- 1381112
TI  - Coagulation dynamics after hemodilution with polyhemoglobin.
AB  - The effect of polyhemoglobin solution (PHS), a candidate erythrocyte cell
      substitute, on blood coagulation, was investigated. Whole blood samples from six
      male Sprague-Dawley rats were diluted in vitro 3:1, 1:1 and 1:3 with normal
      saline solution, stroma-free hemoglobin (SFH) (7 grams of hemoglobin per
      deciliter), PHS (14 grams of hemoglobin per deciliter) or 5 percent bovine
      albumin (ALB) and tested with a thrombelastograph (TEG) for effects of
      hemodilution on coagulation. For in vivo tests, 24 rats were randomly divided
      into four groups of six each and 50 percent of the estimated blood volume was
      replaced with SFH, PHS, ALB or 6 percent hydroxyethyl starch. Blood samples
      collected before and after the hemodilution were tested with a TEG. The TEG
      parameters (r, k, Ma, and fi) were determined and analyzed statistically. At 50
      percent in vitro or in vivo hemodilution, PHS did not cause significant
      alteration (p greater than 0.05) in initial coagulation mechanism, while SFH
      slightly, but significantly (p less than 0.05), accelerated coagulation. Tensile
      strength of formed clot (Ma) did decrease after hemodilution with PHS (p less
      than 0.05), but the effect was attributable to dilutional effect. At moderate
      hemodilution (50 percent), PHS does not seem to cause undue coagulopathy in this
      rat model.

PMID- 1381113
TI  - Use of absorbable clips for tube-saving laparoscopic operations in tubal
      pregnancies.

PMID- 1381114
TI  - Genetic analyses of mammalian ear development.

PMID- 1381115
TI  - Santiago Ramon y Cajal and methods in neurohistology.
AB  - Controversy, misunderstanding or uninformed opinion abound over the extent to
      which the great Spanish neurohistologist, Santiago Ramon y Cajal, specified his
      staining methods in his analytical papers, the methods by which he analysed and
      presented his data, and the microscopes available to him. In this paper, we have
      attempted to outline the information on these points that we have been able to
      obtain from a detailed examination of his writings and a study of the evidence
      remaining in the Cajal Museum in Madrid.

PMID- 1381116
TI  - Three-dimensional images of Ramon y Cajal's original preparations, as viewed by
      confocal microscopy.
AB  - The drawings prepared by Santiago Ramon y Cajal have an inherent beauty as well
      as being accurate and arose partly as a result of the difficulty contemporary
      photographic methods had in reproducing informative images of the thick sections
      he used. Modern methods are better and in this brief article Alan Boyde presents
      some three-dimensional images of these historical preparations, generated by
      confocal microscopy.

PMID- 1381117
TI  - Differential effects of ACh on cardiac pacemaker cells.

PMID- 1381118
TI  - Pain and somatosensory activation.

PMID- 1381119
TI  - Pain and activation in the thalamus.

PMID- 1381120
TI  - Immune activation and neuronal injury in AIDS.

PMID- 1381121
TI  - Mechanoelectrical transduction by hair cells.
AB  - Hair cells of the inner ear are one of nature's great success stories, appearing
      early in vertebrate evolution and having a similar form in all vertebrate
      classes. They are specialized columnar epithelial cells, with an array of
      modified microvilli or stereocilia on their apical surface, interconnected by a
      series of linkages. The mechanical stimulus causes deflection of the stereocilia,
      stretching linkages between them, and opening the mechanotransducer channels. On
      a slower timescale, hair cells adapt in order to maintain optimum sensitivity,
      with an adaptation motor within the stereocilia acting to keep the resting
      tension on channels constant.

PMID- 1381122
TI  - Changes in Ca(2+)-binding proteins in human neurodegenerative disorders.
AB  - The cellular distribution of Ca(2+)-binding proteins has been extensively studied
      during the past decade. These proteins have proved to be useful neuronal markers
      for a variety of functional brain systems and their circuitries. Their major
      roles are assumed to be Ca2+ buffering and transport, and regulation of various
      enzyme systems. Since cellular degeneration is accompanied by impaired Ca2+
      homeostasis, a protective role for Ca(2+)-binding proteins in certain neuron
      populations has been postulated. As massive neuronal degeneration takes place in
      several brain diseases of humans, such as Alzheimer's disease, Parkinson's
      disease and epilepsy, changes in the expression of Ca(2+)-binding proteins have
      therefore been studied during the course of these diseases. Although the data
      from these studies are inconsistent, the detection and quantification of Ca(2+)
      binding proteins and the neuron populations in which they occur may nevertheless
      be useful to estimate, for example, the location and extent of brain damage in
      the various neurological disorders. If future studies advance our knowledge about
      the physiological functions of these proteins, the neuronal systems in which they
      are expressed may become important therapeutical targets for preventing neuronal
      death in an array of neurodegenerative diseases.

PMID- 1381124
TI  - [Early detection of prostatic cancer].

PMID- 1381123
TI  - Neurotransmitter transporters (plus): a promising new gene family.
AB  - Neurotransmitter transporter genes encode proteins with 12 putative transmembrane
      regions, which mediate Na(+)-dependent reaccumulation of released
      neurotransmitters into presynaptic terminals and are the sites of action of
      important abused and therapeutic drugs. Studies of these genes show promise for
      improving our understanding of transport mechanisms and modes of drug action, and
      may even uncover previously unanticipated neurotransmitters.

PMID- 1381125
TI  - [After care of prostatic cancer].

PMID- 1381126
TI  - A rapid method for detection of Yersinia enterocolitica serotype O:3 in pig feces
      using monoclonal antibodies.
AB  - A simple colony immunoblotting method using monoclonal antibodies (MAbs) was
      developed to detect Y. enterocolitica serotype O:3 in pig feces. One of the MAbs
      studied was able to detect single colonies of the organism in the presence of
      calculated 3.1 x 10(8) heterologous organisms in pig feces. The MAb was found to
      be specific for the lipopolysaccharide (LPS) O-antigens of Y. enterocolitica
      serotype O:3. No significant cross-reactivity was found against a variety of
      closely related serotypes and Gram-negative organisms. The MAb could also be used
      in a slide agglutination test and an indirect fluorescence antibody assay for
      rapid identification of Y. enterocolitica serotype O:3.

PMID- 1381127
TI  - Purification and adhesion receptor phenotype of ovine bone marrow-derived
      haemopoietic colony-forming cells.
AB  - Ovine haemopoietic progenitor cells that form colonies (CFC) in soft agar
      cultures were compared to more mature bone marrow cells for their level of
      expression of the adhesion receptor molecules ovine (ov) CD44, ov CD11a (LFA-1)
      and ov CD58 (LFA-3) as well as the 175-antigen using specific monoclonal
      antibodies. Ov CD44, ov CD11a and ov CD58 were expressed on all CFC of the
      myeloid (non-erythroid) series, whereas ov CD44 and ov CD11a expression was very
      low or absent from a small number of blast and erythroid series CFC. Within the
      mature non-erythroid population of myeloid cells, neutrophils retained a low
      level of expression of ov CD11a. Most CFC representing all lineages strongly
      expressed the ov CD44 antigen. In contrast, the majority of CFC lacked the 175
      antigen, as did bone marrow lymphocytes, basophils and mast cells. This property
      of CFC was exploited in a negative selection technique using panning and
      immunomagnetic beads to select CFC from other bone marrow cells with a 116-125
      fold enrichment, 12-14% purity and 29-40% yield. These results demonstrate that
      ovine CFC express some of the molecules necessary to allow adhesion to
      haemapoietic stromal cells and vascular endothelium in the tissues. Future
      studies will concentrate on the function of the adhesion receptor molecules in
      medullary and extra-medullary haemopoiesis and inflammatory cell development in
      sheep.

PMID- 1381128
TI  - Changes in cytokeratin expression accompany squamous metaplasia of the human
      respiratory epithelium.
AB  - To determine the characteristics of metaplastic changes of the nasal respiratory
      epithelium, the distribution of individual cytokeratins (CKs) was studied
      immunohistochemically and by two-dimensional gel electrophoresis. The authors
      define four types of changes of the normal pseudostratified columnar epithelium:
      (1) transitional pseudostratified epithelium (first unusual CK.: no. 13); (2)
      stratified columnar epithelium (increased expression of CKs 4 and 13; CKs 7, 8,
      18 and 19 reduced); (3) stratified squamous epithelium, nonkeratinized
      (appearance of CK 16); and (4) stratified squamous epithelium, keratinized
      (expression of CKs 1 and 10, variable CK5 and 14 patterns in basal cells). These
      phenotypes were found simultaneously within single specimens, resulting in
      apparent overall variability in the immunohistochemical staining patterns.
      Spatially, changes in CK expression towards "normal" parts were not abrupt but
      rather gradual. Biochemical data confirmed the immunohistochemical findings and
      added CK 6 to the pattern of altered nasal mucosa. The findings of this study
      suggest a stem cell metaplasia in the nasal epithelium which is based on its
      inherent bimodal developmental programme. A gradual loss of normal respiratory
      epithelial differentiation, as seen by the loss of CKs 7, 8, and 18, was
      paralleled by the appearance of squamous epithelial type CKs, e.g. the expression
      of CKs 1, 10 and 13. Basal cell types CKs 5, 14, 17 and 19 were maintained during
      this process. Implications of these results for general concepts of CK expression
      in the metaplastic process are discussed.

PMID- 1381131
TI  - Establishment and characterization of a human papillary thyroid carcinoma cell
      line with oxyphilic differentiation (ONCO-DG 1).
AB  - In the present study the establishment and characterization of a new oxyphilic
      papillary thyroid carcinoma cell line--ONCO-DG1- is given. With
      immunohistological, histochemical and flow cytometric methods, ONCO-DG 1 cells
      revealed features of epithelial differentiation. Furthermore the cells formed von
      Kossa-positive deposits resembling psammoma bodies in monolayer and spheroid
      culture until late passages. The tumor cell line is now in the 40th subculture.
      Because of the ability to form multicellular tumor spheroids (MCTS), this cell
      line is a good model for examining the interaction between thyroid tumor cells
      and confluent human endothelial cells on extracellular matrix in vitro. It is
      also suitable for xenotransplantation studies, because it is tumorigenic in NMRI
      nude mice in vivo.

PMID- 1381130
TI  - Testicular sex cord-stromal lesions: immunohistochemical analysis of cytokeratin,
      vimentin and steroidogenic enzymes.
AB  - We have studied immunolocalization of all steroidogenic enzyme involved in sex
      steroids biosynthesis, P-450 side chain cleavage (P-450scc), 3 beta hydroxy
      steroid dehydrogenase (3 beta-HSD), P-450 17 alpha hydroxylase (P-450(17 alpha))
      and P-450 aromatase (P-450arom) and that of vimentin and cytokeratin in 14 cases
      of testicular sex cord-stromal tumours (6 Leydig cell tumours, 5 Sertoli cell
      tumours, 2 fibromas and 1 granulosa cell tumour) as well as 4 cases of
      hyperplasia (2 Leydig and 2 Sertoli). Leydig cell tumour expressed all four
      steroidogenic enzymes examined, indicating that this tumour can synthesize
      oestrogen from cholesterol. In 2 cases of Sertoli cell tumour, the tumour cells
      with clear cytoplasm and without Reinke's crystals expressed P-450ssc, 3 beta-HSD
      and P-450(17 alpha), suggesting the capability of androgen production in these
      tumour cells. Fibromas and granulosa cell tumour were negative for the enzymes
      examined. In immunohistochemistry of intermediate filaments, Leydig cell tumours
      demonstrated only vimentin. Sertoli cells in hyperplasia and non-neoplastic
      testis expressed only vimentin but Sertoli cell tumours expressed both
      cytokeratin and vimentin. Cytokeratin immunoreactivity was correlated with
      morphological epithelial differentiation in Sertoli cell tumour. These findings
      in testicular Sertoli cell tumour are considered to represent the multiple
      differentiation capacity of this neoplasm. Immunohistochemical study of
      steroidogenic enzymes and intermediate filaments provided new insight into
      neoplastic steroidogenesis and the differentiation capacity of testicular sex
      cord-stromal neoplasms.

PMID- 1381129
TI  - Keratin profiles in normal/hyperplastic prostates and prostate carcinoma.
AB  - Immunoreactivities in 25 cases of prostatic adenocarcinoma and 10
      normal/hyperplastic prostates were investigated in methacarn-fixed, paraffin
      embedded serial sections using a panel of nine anti-keratin monoclonal antibodies
      (mAbs); 34 beta E12, CK8.12, 312C8-1, CK4.62, RPN1165, RPN1162, 35 beta H11, CK5,
      M20, and one of anti-actin mAb, HHF35. In normal/hyperplastic prostates, RPN1162,
      35 beta H11, CK5 and M20 stained luminal cells without staining basal cells, and
      34 beta E12, CK8.12 and 312C8-1 stained basal cells but not luminal cells. Other
      mAbs, CK4.62 and RPN1165, stained basal cells as well as luminal cells. All of
      the mAbs labelling luminal cells stained cancer cells with variable frequencies
      in a manner unrelated to the grade of tumour differentiation. Of the prostate
      cancer cases 92% were scored positive with M20, 84% with 35 beta H11, 80% with
      CK5, 68% with CK4.62, 60% with RPN1165 and 4% with RPN1162. However, basal cell
      specific keratins labelled with 34 beta E12, CK8.12 and 312C8-1 were totally
      negative in the cancer cells. HHF35 showed no labelling in normal, hyperplastic
      or neoplastic epithelial cells of the prostate. Our findings indicate that the
      major part of the cells of prostatic adenocarcinomas have keratin phenotypes
      similar to luminal cells but not basal cells, and that no myoepithelial
      differentiation can be detected in epithelial cell of the prostate. Thus, mAbs
      for keratins facilitate the identification of epithelial cell phenotypes in
      normal, benign and malignant conditions of the prostate.

PMID- 1381132
TI  - Pancreatic islet transplantation: isolation, separation, and
      microvascularization.
AB  - Twenty years ago Ballinger and Lacy were the first to report cure of experimental
      diabetes in rats after free transplantation of isolated pancreatic islets. In a
      remarkable number of experimental studies on transplantation of isolated islets
      of Langerhans reversal of diabetes and restoration of normal glucose metabolism
      has been achieved in rodents. However, studies in larger animals and clinical
      attempts have been less successful. Beside graft rejection, the isolation and
      purification of a sufficient mass of islets have been identified as major
      obstacles. In addition, insufficient revascularization is thought to be, in part,
      responsible for early graft failure. Recent developments allow for consistently
      high yields of isolated islets using an automated method, in particular for
      isolation of human pancreatic islets. Furthermore, a variety of techniques have
      been implemented during the past years improving purification, including gradient
      separation, fluorescence-activated sorting, magnetic microsphere extraction and
      cryopreservation. Revascularization of the islet grafts may be enhanced by
      selection of adequate sites for transplantation and/or by supportive application
      of angiogenic peptides. Progress achieved during the past years allow for new
      hope for successful clinical islet transplantation.

PMID- 1381133
TI  - [Value of 24-hour blood pressure measurement in patients with arterial
      hypertension, left heart enlargement and increased cardiac risk].
AB  - Non-invasive 24-h blood pressure and a 24-h electrocardiogram were recorded in 45
      normotensive and 97 matched, untreated, hypertensive subjects, with and without
      echocardiographic signs of left-ventricular hypertrophy and without signs of
      coronary artery disease. Forearm vascular resistance was calculated from mean
      blood pressure and postischemic blood flow, which was measured by venous
      plethysmography. Systolic ambulant 24-h blood pressure exhibited the closest
      correlation with left-ventricular mass index in hypertensives (r = 0.48; p less
      than 0.001). No relation could be found between blood-pressure fall overnight and
      left-ventricular hypertrophy. Blood-pressure variability was significantly higher
      in hypertensive subjects. Furthermore, systolic 24-h blood pressure significantly
      correlated with the rate of ventricular arrhythmias in hypertensives. Casual
      blood pressure exhibited no comparable correlations. A significant close
      correlation between 24-h blood pressure and vascular resistance was identified in
      hypertensives. Furthermore, left-ventricular mass index and vascular resistance
      were correlated (in hypertensives: r = 0.32; p less than 0.01). This finding
      speaks for a parallel development of total peripheral resistance and left
      ventricular hypertrophy in essential hypertension. The close relationships
      between ambulatory 24-h blood pressure, left-ventricular hypertrophy, ventricular
      arrhythmias, and vascular resistance demonstrates the high diagnostic and,
      possibly, the prognostic value of long-term blood-pressure measurement.

PMID- 1381134
TI  - Intrinsic organization of the paramedian pontine reticular formation of the cat.
AB  - A morphoquantitative analysis was carried out to clarify the cytoarchitectural
      organization of the paramedian pontine reticular formation (PPRF) which is
      considered to be an important site in the control of eye movements. The study was
      carried out on the cat, using the Golgi staining method. The topographic position
      and detailed structure of the neurons were demonstrated using morphoquantitative
      methods. On the basis of their neuronal arborization, fusiform neurons and two
      types of multipolar cells were identified. Fusiform neurons show dendrites which
      are given off from the two poles of the small- to medium-sized cell body. The
      arborization generally runs caudorostrally, ending inside the PPRF. These neurons
      are ubiquitous. Type 1 multipolar neurons, the most frequent elements of the
      neuronal population (60%), have a small- to large-sized cell body from which 2 or
      3 primary spiny dendrites and the axon emerge. Their dendritic field is oval and
      generally oriented in the vertical plane. These neurons are scattered everywhere
      in the PPRF. Type 2 multipolar cells are large neurons endowed with numerous
      primary spiny dendrites constituting a wide round dendritic field and with a
      thick axon. They are located almost exclusively at the boundaries of the PPRF and
      preferentially in the caudal region. The characteristics of the neurons suggest
      that the fusiform cells may play an interneuronal role, while the multipolar
      neurons could have both a projective function and an important receptive role for
      the afferent fibers to the PPRF. The lack of homogeneity found among the
      multipolar neurons is in agreement with the variety of projective elements shown
      by functional investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381135
TI  - [Morphometric analysis in the rat spinal cord following peripheral nerve
      transection with the use of MAP2 immunohistochemistry].
AB  - The physiological function of the spinal cord is regulated by two different kinds
      of information, namely, afferent inputs from the primary sensory fibers and
      descending inputs from the brain. The former conveys the sensory information from
      the peripheral region via the dorsal root ganglia to spinal interneurons or
      directly to motor neurons and brings about the voluntary and/or involuntary
      muscle movement. In the present study, the time-related changes in the
      dendrocytoarchitecture of the rat spinal cord following the transection of
      afferent and efferent connections from/to the peripheral organs were observed by
      using immunohistochemistry for microtubule-associated protein 2 (MAP2) and Nissl
      staining. To investigate the changes quantitatively, morphometric analyses were
      performed on the section of gray matter of tissue samples stained with MAP2
      antisera. One to 24 weeks after hemitransection of the dorsal and ventral roots,
      a remarkable reduction in the area and progressive changes in the shape of the
      gray matter were seen in both the anterior and posterior horns on the lesioned
      side. These changes were found to be due to the reduction of the width of the
      anterior and posterior horns on the lesioned side rather than of the height. At
      the later postoperative stage, atrophy of the Fasciculus gracilis and
      disappearance of motoneurons on the lesioned side were recognized in Nissl
      stained tissue samples.

PMID- 1381136
TI  - Cross-reactivity of a commercial chemiluminescence immunoassay for human
      chorionic gonadotropin with the free beta-subunit.
AB  - An enhanced chemiluminescence immunoassay for the determination of serum human
      chorionic gonadotropin (HCG) in specimens from oncology patients has been
      assessed with respect to its cross-reactivity with the free HCG beta-subunit (HCG
      beta). The assay, standardized against the First International Reference
      Preparation 75/537, had a cross-reactivity with the free beta-subunit of 625%
      (molar basis). Therefore this assay achieves high sensitivity for the detection
      of either intact HCG or free HCG-beta in serum of patients with seminomatous or
      nonseminomatous testicular cancers. Results of both assays, the in-house
      immunoradiometric assay (+HCG-beta) and the Amerlite HCG-60 assay, showed a close
      correlation (R = 0.854-0.960) when serum samples from tumour patients were
      analyzed. Moreover, the content of free beta-subunit determined in a specific HCG
      beta assay, could be quantitatively measured in the enhanced chemiluminescence
      immunoassay. Thus, this assay is suitable for oncology use, but also highlights
      the limitations of measuring HCG in serum samples.

PMID- 1381138
TI  - Cytokeratins in intracranial and intraspinal tissues.
AB  - The intermediate filament distribution pattern in cells and tissues of
      vertebrates reflects their differentiation or functional specialization state,
      their histogenesis, and their malignant transformation. In the case of
      cytokeratins, the characteristic epithelial intermediate filaments representing a
      complex group of about 30 polypeptides, extensive attention has been given to
      their expression in diverse epithelial and epithelioid cells. However, little is
      known about their distribution during fetal development and in neuroectodermal
      cells. This review specifically focuses on the data concerning cytokeratin
      expression in intracranial and intraspinal tissues, as expressed alone or as
      coexpressed with other intermediate filament proteins. Furthermore, the
      expression pattern of individual cytokeratin polypeptides was investigated by
      immunocytochemistry in diverse human and animal tissues using a broad panel of
      monoclonal antibodies. Only the cytokeratins typical of simple epithelia with the
      primary keratin pair 8/18 as a significant component have been detected in
      neuroectodermal tissues such as the choroid plexus and ciliary body epithelia,
      the retinal pigment epithelium, the subcommissural organ, and the ependymal cell
      clusters in fetal pineal gland (only in humans) as well as in various
      "unspecialized" ependymal cells of brain ventricles and spinal cord ependyma.
      Focal cytokeratin 19 expression in rat ciliary body and ventricle ependyma
      represents a rare exception. In addition, a group of intracranial and intraspinal
      tissues with controversial histogenesis express solely the cytokeratins 8 and 18:
      endocrine pituitary cells, arachnoid cells, and corneal endothelium. In most
      cases of tissues with neuroectodermal derivation, coexpression of cytokeratins
      and vimentin, or triple expression of cytokeratin, vimentin, and GFAP (fetal and
      neonatal choroid plexus of humans, rat and guinea pig ependymal cells in the
      neighborhood of the subcomissural, folliculostellate cells of human and guinea
      pig pituitary) is detectable. The coexpressions are discussed in the light of
      several hypotheses based on morphological and functional data concerning
      intermediate filament protein expression. Both the occurrence of more than one
      intermediate filament protein and the individual cytokeratin composition in the
      corresponding tumors of neuroectodermal origin reflect, in principle, the
      patterns found in their normal tissues. In the fetal neuroectodermal tissues
      studied, the cytokeratin pair 8/18 is the first one to be expressed during
      embryonic development.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1381137
TI  - Effects of dorsal root entry zone lesions on CSF and plasma neuropeptides and
      catecholamines.
AB  - Effects of dorsal root entry zone lesions (DREZLs) on cerebrospinal fluid (CSF)
      and plasma concentrations of neuropeptides, catecholamines, and cyclic
      nucleotides were studied in 9 patients with intractable chronic pain. Contents of
      beta-endorphin-like-material in CSF decreased in all patients 12-17 days
      following DREZLs during which complete to good pain relief was achieved. Contents
      of beta-endorphin-like-material in CSF increased again about one month after
      DREZLs in two and remained unchanged in one of three patients tested, who
      complained of partial reappearance of pain. Contents of beta-endorphin-like
      materials in plasma showed no significant changes after DREZLs. Substance P,
      noradrenaline, adrenaline, and cyclic nucleotide levels in both CSF and plasma
      were variable among the subjects and did not change significantly following the
      operations. Thus, the results suggest that production of beta-endorphin-like
      material in the central nervous system is decreased by DREZL, though the increase
      in its turn-over might not be neglected. The mechanisms of the decrease in
      contents of beta-endorphin-like-material in CSF after DREZLs were discussed in
      terms of our current knowledge of pain and pain inhibitory systems.

PMID- 1381139
TI  - Improved detection of antibodies to hepatitis C virus using a second generation
      ELISA.
AB  - A screening assay for the detection of antibodies to hepatitis C virus (HCV);
      ORTHO HCV ELISA Test System, Second Generation, was compared with the currently
      licensed c100-3 based test (ORTHO HCV ELISA Test System). The second generation
      ELISA differs from the c100-3 based assay in that it detects circulating
      antibodies to both structural (nucleocapsid) and non-structural (NS3/NS4) HCV
      proteins. Specimens tested consisted of a cohort of 35 patients diagnosed with
      non-A, non-B hepatitis (NANBH) and 3971 presumably healthy volunteer blood
      donors. Second generation ELISA demonstrated significantly greater clinical
      sensitivity in patients with acute phase NANBH (80% vs. 60%) as well as chronic
      disease (88% vs. 72%). Additional specimens reactive only in second generation
      ELISA, demonstrated reactivity to HCV antigens c33c and/or c22-3 in supplemental
      testing by the Chiron HCV RIBA Assay System. The second generation ELISA also
      detected additional RIBA reactive volunteer blood donors (0.18% of the population
      tested) that were nonreactive in first generation ELISA. This data indicated that
      second generation ELISA would detect approximately 2 additional anti-HCV reactive
      donors per 1,000 screened. Specificities obtained with this low risk population
      were 99.6% for first generation and 99.7% for second generation ELISA.

PMID- 1381140
TI  - A novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.

PMID- 1381142
TI  - Mechanism of irregular parasystole: differentiation of second-degree entrance
      block from electrotonic modulation.

PMID- 1381141
TI  - Transient coronary stenosis associated with arrhythmia and ischemia 24 hours
      after reperfusion.
AB  - We examined the electrophysiologic sequelae of transient reductions in coronary
      blood flow (CBF) in conscious dogs. Animals were instrumented to measure arterial
      pressure, heart rate, repetitive extrasystole threshold (RET), and CBF before
      coronary stenosis, during 90 minutes of a 50% reduction in CBF, and at 1, 24, 48,
      and 72 hours after reperfusion. RET was decreased at 24 and 48 hours but returned
      to baseline by 72 hours after reperfusion. Frequent ventricular ectopic activity
      (VEA), absent during the control period, was noted during stenosis and at 1, 24,
      and 48 hours after reperfusion. beta-Adrenergic blockade (metoprolol) normalized
      the decreased RET at 24 hours. Addition of alpha 1-adrenergic blockade (prazosin)
      abolished VEA. Endocardial blood flow in the posterior papillary muscle of the
      left ventricle was reduced by 52 +/- 9% during stenosis, was similar to baseline
      levels by 1 hour after reperfusion, and decreased by 39 +/- 5% at 24 hours. We
      conclude that episodes of modest coronary artery stenosis may be followed by
      electrophysiologic changes indicative of increased vulnerability to malignant
      ventricular arrhythmias.

PMID- 1381143
TI  - Combination chemotherapy and radiation for palliation of hepatocellular
      carcinoma.
AB  - Twenty seven patients with hepatocellular carcinoma were treated by sequential
      methotrexate (75 mg/m2) and 5-fluorouracil (5-FU) (750 mg/m2) on day 1 followed
      on days 8-36 by external beam radiotherapy (total dose 30 cGy). The response was
      assessed by liver size on clinical examination. One patient had complete
      response, and six patients had partial response. The overall response to the
      treatment was 25.9%. More than a 50% reduction in serum alfa-fetoprotein level
      was noted in 66.6% patients. Seventy-one percent of patients had palliation of
      pain following therapy. The median survival of responders was 11 months and of
      nonresponders, 2 months. Radiation was discontinued in two patients who developed
      radiation hepatitis. Additional trials with different dosages and schedules are
      needed to fully evaluate this form of therapy.

PMID- 1381144
TI  - Extragonadal abdominal germ cell cancers.
AB  - The charts of eleven patients with abdominal germ cell tumors were reviewed; one
      had a seminoma. They all had normal testes by physical examination. Therapy
      consisted of cisplatin-based chemotherapy and, in some cases, surgical debulking.
      A complete clinical response occurred in seven patients (63%). Two patients
      relapsed after achieving pathology complete responses and died of progressive
      disease despite second-line chemotherapy. All patients that failed to achieve a
      complete clinical response died of progressive disease. Five patients (45%) are
      long-term disease-free survivors, having no recurrence 4-10 years from the time
      of the diagnosis (median 6 years). The outcome for this group of patients did not
      differ significantly from that for patients with mediastinal germ cell tumors in
      this institution. They do not fare as well as patients with testicular cancer.

PMID- 1381145
TI  - Radiation therapy in a case of systemic mastocytosis: evaluation of histamine
      levels and mucosal effects.
AB  - Plasma histamine levels were obtained during palliative radiation therapy of the
      spine involved with systemic mastocytosis in a 68-year-old woman. Baseline plasma
      histamine levels were obtained before irradiation and compared to levels obtained
      on the third, fifth, eighth, and tenth treatment days. Despite concerns regarding
      histamine release with mast cell destruction following irradiation, plasma
      histamine levels remained within normal limits. No change in dermatologic or
      other systemic manifestations were observed. No untoward systemic or localized
      sequelae associated with mast cell degranulation in response to the administered
      large field of radiation was observed. Effective palliation was accomplished, and
      it was concluded that radiation therapy can effectively be applied in treatment
      of systemic mast cell disease without significant morbidity.

PMID- 1381146
TI  - CFTR!
AB  - Cystic fibrosis (CF) is a fatal genetic disease primarily affecting Caucasians,
      although cases have been reported from other ethnic groups. CF has a complex
      etiology, but it is chiefly a disease of electrolyte transport and is
      characterized by defects in fluid secretion by several epithelia, including the
      sweat duct, exocrine pancreas, and the pulmonary airways. The link between CF and
      a defect in cAMP-mediated Cl- transport in secretory epithelia was established in
      the early 1980s. Since then, numerous electrophysiological studies have focused
      on the characterization and regulation of individual Cl- channels underlying the
      macroscopic Cl- currents of secretory epithelia in the airways, sweat ducts, and
      gut. In this review the results of these studies in the light of current
      knowledge of the function of the CF gene product, the CF transmembrane
      conductance regulator (CFTR) protein, will be analyzed. The CFTR protein is a
      member of a family of ATP-binding proteins that act as unidirectional solute
      pumps. These proteins are membrane spanning, are found in both prokaryotic and
      eukaryotic cells, and have two ATP-binding domains. The family includes the p
      glycoproteins that are involved with the expression of multidrug resistance in
      certain tumor cells. The majority of CF chromosomes (70%) have a single codon
      deletion that translates to a missing phenylalanine residue at position 508
      (delta F508) of the protein. Unique for this family of proteins, the CFTR protein
      possesses an additional highly charged domain (the R domain) containing several
      consensus polypeptide sequences for kinase phosphorylation. Although CFTR bears
      structural resemblance to this family of ATP-dependent pumps, overexpression of
      the protein in a variety of different cell types is associated with the
      appearence of a cAMP-sensitive Cl- channel. We critically examine current
      information concerning the structure-function relationships of the CFTR protein
      obtained from both electrophysiological and biochemical approaches. We also
      summarize recent evidence suggesting that the CFTR protein may act as a pump and
      a channel, a hypothesis in keeping with the multifaceted nature of the disease.

PMID- 1381147
TI  - Oncotic pressure regulates gene transcriptions of albumin and apolipoprotein B in
      cultured rat hepatoma cells.
AB  - The mechanism of the accelerated syntheses of albumin and apolipoprotein B (apo
      B) in response to decreased oncotic pressure was investigated in cultured rat
      hepatoma H4-II-E cells. Addition of dextran (mol wt 6-9 x 10(4)) to the culture
      medium decreased the levels of albumin and apo B mRNAs in an oncotic pressure
      dependent manner. The reductions of both mRNAs were attenuated with increase in
      the molecular weight of dextran, which resulted in a decrease in oncotic
      pressure. Addition of macromolecule increased the viscosity in medium; however,
      alteration of viscosity appeared not to correlate with albumin and apo B mRNA
      levels. Transcriptional run-on assays with isolated nuclei from dextran-treated
      vs. untreated hepatoma cells indicated that the changes in steady-state mRNA
      levels were mainly controlled at the transcriptional step. Treatment with
      cycloheximide increased albumin mRNA to the basal level, which was effectively
      suppressed by dextran, and resulted in superinduction of apo B mRNA. These
      changes occurred primarily at the transcriptional step. These results suggest
      that regulations of the expressions of the albumin and apo B genes for adaptive
      increases in the mRNAs may require the continued synthesis of a labile protein(s)
      or a limiting transcription factor(s). We conclude that oncotic pressure plays an
      important role in regulation of expression of the albumin and apo B genes at the
      transcriptional step.

PMID- 1381148
TI  - Low K+ increases Na(+)-K(+)-ATPase alpha- and beta-subunit mRNA and protein
      abundance in cultured renal proximal tubule cells.
AB  - Studies from this laboratory demonstrate that LLC-PK1/Cl4 cells, a cultured renal
      cell line, respond to incubation in low-K+ medium by coordinately increasing
      abundance of both alpha- and beta-subunits of Na(+)-K(+)-ATPase but increase only
      beta- and not alpha-mRNA levels (Lescale-Matys et al. J. Biol. Chem. 265: 17935
      17940, 1990) and that alpha-abundance is likely increased as a result of
      increased efficiency of alpha-mRNA translation (L. Lescale-Matys and A. A.
      McDonough. J. Cell Biol. 111: 311A, 1990). The aim of this report was to
      determine if nontransformed kidney cells would respond to low K+ in a similar
      manner. We incubated primary cultures of rat proximal tubule cells in low K+
      (0.25 mM) for up to 24 h to address this aim. Na(+)-K(+)-ATPase activity,
      measured enzymatically, and abundance of alpha- and beta-subunits, measured by
      immunoblot, were increased significantly and coordinately by 8 h of low K+, and,
      by 24 h of low K+, these parameters were increased to 2.17 +/- 0.34 (activity),
      2.03 +/- 0.21 (alpha), and 2.39 +/- 0.48 (beta)-fold over control.
      Pretranslationally, beta-mRNA, measured by Northern blot analysis, increased to
      1.76 +/- 0.35 after 3 h of low K+ and to 3.4 +/- 0.75-fold over control after 24
      h of low K+. The increase in alpha-mRNA was smaller and delayed compared with the
      beta-mRNA response, but it was sufficient to account for the observed increase in
      alpha-protein and Na(+)-K(+)-ATPase activity at steady state: alpha-mRNA
      increased to 1.27 +/- 0.09 after 6 h and to 1.91 +/- 0.41-fold over control after
      24 h in low K+. We conclude that the accumulation of sodium pumps in cultured
      renal proximal tubule cells, unlike LLC-PK1 cells, can be accounted for by
      increases in both alpha- and beta-subunit mRNA levels.

PMID- 1381149
TI  - Right-angle light scattering to assay basal and regulated plasma membrane Cl-
      conductances.
AB  - We describe a simple and rapid technique for assaying both constitutive and
      regulated plasma membrane Cl- conductances. The method uses right-angle light
      scattering to measure the rate of swelling of cells in suspension, in which the
      anion conductance is rate limiting for swelling, due to introduction of high
      plasma membrane cation conductance using gramicidin. The technique was verified
      using Chinese hamster ovary cells and mouse L cells, both stably transfected with
      the cystic fibrosis transmembrane conductance regulator (CFTR), to confer a
      specific cAMP-activated Cl- conductance not normally present in these cell types.
      In agreement with results obtained using other methods for assaying Cl-
      permeability in these cells, forskolin stimulated a significant increase in
      plasma membrane Cl- conductance in CFTR-expressing cells, as indicated by an
      increase in light scattering. That the enhanced light scattering by the cells was
      the result of cell swelling due to NaCl influx was shown by ion substitution
      experiments, in which no forskolin-induced increase in light scatter occurred in
      N-methyl-D-glucamine Cl- or Na+ gluconate medium. Enhanced light scattering was
      also observed in both CFTR-expressing and control cells stimulated with the Ca2+
      ionophore, ionomycin. Extracellular anion substitution, to exploit the inwardly
      directed halide gradient utilized in this protocol, enabled determination of the
      anion selectivities of both the cAMP- and Ca(2+)-activated Cl- channels. Thus
      this technique provides a simple optical method for rapidly assaying not only
      constitutive and regulated Cl- conductance pathways but also their anion
      selectivities.

PMID- 1381150
TI  - Stretch-dependent regulation of atrial peptide synthesis and secretion in
      cultured atrial cardiocytes.
AB  - We have developed a novel system to study stretch-dependent secretion of atrial
      natriuretic peptide (ANP) using cultured neonatal rat atriocytes in vitro.
      Application of tension (i.e., 2 sequential stretches) to cells grown on a
      flexible culture surface effected a dose-dependent increase in immunoreactive
      (ir) ANP release into the medium. Analysis of atriocyte cytoplasmic RNA 24 h
      poststretch revealed an increase in ANP mRNA levels of about ninefold relative to
      the unstretched controls. Medium ATP levels, measured as an index of cellular
      damage, were similar in control and stretched cells. Furthermore, cooling the
      cultures to 0 degrees C suppressed both basal as well as stretch-stimulated
      release. These findings argue against cellular damage and nonspecific release of
      irANP as an explanation for the increase in medium immunoreactivity. Stretch was
      incapable of amplifying the secretory response to prostaglandin F2 alpha,
      suggesting possible overlap in the pathways whereby these stimuli effect release
      of the peptide. The calcium channel blocker verapamil had no effect on stretch
      dependent irANP release, whereas calmidzolium, a calmodulin inhibitor, suppressed
      basal as well as stretch-dependent secretion, implying a potentially important
      relationship between intracellular calcium metabolism and irANP release.

PMID- 1381151
TI  - NADPH diaphorase and nitric oxide synthase colocalization in enteric neurons of
      canine proximal colon.
AB  - Considerable evidence has recently been presented that suggests that nitric oxide
      (NO) is a nonadrenergic noncholinergic (NANC) neurotransmitter in
      gastrointestinal tissues. One of the criteria that must be satisfied before this
      hypothesis can be accepted is that enteric neurons must be shown to contain the
      enzymatic apparatus necessary to synthesize NO. Specific antibodies have been
      developed for NO synthase (NOS) isolated from rat cerebellum, and studies have
      shown that NOS copurifies and colocalizes with NADPH diaphorase activity, a
      commonly used neural marker. We used antibodies raised against the cerebellar NOS
      to determine the distribution of NOS-like immunoreactivity (NOS-LI) in enteric
      neurons of the canine proximal colon. We also tested whether NADPH diaphorase
      staining would label the population of neurons containing NOS-LI in this species.
      A subpopulation of neurons in myenteric and submucosal ganglia displayed NOS-LI
      and were colabeled with NADPH diaphorase. Labeled neurons had morphological
      characteristics similar to the Dogiel type I morphology. Cryostat sections showed
      NOS-positive nerve trunks throughout the circular and longitudinal muscle layers,
      but a high density of NOS-LI was observed within the submucosal pacemaker region,
      as predicted from physiological studies. These studies provide the first
      morphological support for the hypothesis that NO serves as a NANC
      neurotransmitter in the canine colon. The study also shows that the NADPH
      diaphorase reaction provides a useful method to label cells with NOS-LI.

PMID- 1381152
TI  - Bronchial epithelial cells release neutrophil chemotactic activity in response to
      tachykinins.
AB  - The purpose of this study was to determine whether substance P (SP), neurokinin A
      (NKA), and neurokinin B (NKB) induce the release of neutrophil chemotactic
      activity (NCA) from bovine bronchial epithelial cells (BBEC) and whether neutral
      endopeptidase (NEP), a membrane-bound metalloenzyme that hydrolyzes tachykinins,
      modulates these effects. BBEC monolayers were exposed to SP, NKA, and NKB in the
      absence or presence of phosphoramidon (10(-6) M), a selective NEP inhibitor, for
      72 h. Using a modified blind-well in vitro neutrophil chemotaxis assay, we found
      that tachykinin-exposed BBEC culture supernatant fluids induced significant
      neutrophil chemotaxis compared with supernatants obtained from unstimulated BBEC.
      Maximal effect was observed after 48 h of incubation and at SP concentration of
      10(-13) M [92 +/- 3 (SP) vs. 64 +/- 2 (media) cells/high-power field (HPF), mean
      +/- SE, n = 7, P less than 0.05]. Release of NCA was mediated by the COOH
      terminal of the SP molecule. The rank order of potency of tachykinins in inducing
      release of NCA was SP greater than NKA = NKB. SP-induced response was
      significantly potentiated by phosphoramidon (109 +/- 3 vs. 92 +/- 3 cells/HPF, n
      = 7, P less than 0.05), whereas other proteinase inhibitors had no effect. The
      released NCA was composed of protein and lipid-soluble components. These data
      indicate that mammalian tachykinins induce the release of NCA from BBEC and that
      NEP modulates these effects. We suggest that tachykinins regulate neutrophil
      recruitment into the lower respiratory tract, in part, by inducing the release of
      NCA from airway epithelial cells.

PMID- 1381153
TI  - Cat tracheal gland cells in primary culture.
AB  - Conditions for the primary culture of isolated cat tracheal gland cells were
      established. Cells plated onto glutaraldehyde-fixed gels of rat tail collagen
      grew to confluency after 8 days of culture forming a monolayer of cuboidal cells
      with ultrastructural characteristics of epithelial cells and immunoreactivity to
      antikeratins. Cultured cells synthesized and released radiolabeled high-molecular
      weight glycoconjugates. Glycoconjugate secretion was increased approximately 10%
      in response to the cholinergic agonist, carbachol. Secretion of glycoconjugates
      was unrelated to regulated exocrine secretion, since these cells were devoid of
      secretion granules as assessed by light and electron microscopy. Confluent
      cultures also generated a spontaneous potential difference and short-circuit
      current, which were both inhibited by ouabain and increased by carbachol. This
      suggested gland cells contribute to fluid secretion by active ion-transport
      mechanisms. We also plated cells onto unfixed collagen gels that were released
      from the culture dish at confluency. Cells were columnar with apically oriented
      secretion granules that stained with alcian blue and for blood group A
      immunoreactivity. Secretion of radiolabeled high-molecular-weight glycoconjugates
      was increased 27% by carbachol. These cell culture systems may serve as models to
      investigate glandular secretory mechanisms and their regulation.

PMID- 1381154
TI  - Purification of plasma membranes by aqueous two-phase affinity partitioning.
AB  - A rapid method for purifying rat liver plasma membranes of high purity and yield
      is described. Squashed liver was homogenized in an aqueous polyethylene glycol
      dextran two-phase system. After phase separation and reextraction of the bottom
      phase with fresh top phase, the combined polyethylene glycol-rich top phases were
      affinity partitioned in the presence of borate buffer with new bottom phase
      containing dextran-linked wheat-germ agglutinin. Under these conditions the
      lectin selectively pulled plasma membranes into the dextran-rich bottom phase,
      while other membranes preferentially distributed in the top phase. The lectin
      containing bottom phase was reextracted with fresh top phase before collecting
      the purified plasma membranes by centrifugation. This protocol resulted in a
      preparation that was 30- to 40-fold enriched compared to the homogenate in plasma
      membrane markers for both the apical and basolateral domains and had yields of 55
      70%. The contamination by other membranes was low. The entire procedure was
      completed within 90 min. The method should be useful for purifying plasma
      membranes also from other sources.

PMID- 1381155
TI  - Development of gel staining techniques for detecting the secretion of
      procathepsin D (52-kDa protein) in MCF-7 human breast cancer cells.
AB  - 17 beta-Estradiol stimulates the secretion of the 34- and 52-kDa protein (i.e.,
      cathepsin D and procathepsin D, respectively) from MCF-7 human breast cancer
      cells and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits this estrogen
      stimulated response. A comparison of the effects of 17 beta-estradiol, TCDD, and
      their combinations on the secretion of these two proteins was determined using
      four different assay procedures, namely autoradiographic analysis of the 35S
      labeled proteins (from [35S]methionine) separated by polyacrylamide gel
      electrophoresis (PAGE), densitometric analysis of the silver- and double-stained
      proteins separated by PAGE, and radioimmunoassay of the proteins using
      commercially available antibodies to the 52-kDa protein. The results showed that
      the autoradiographic, staining, and radioimmunoassay procedures gave comparable
      results with only a few minor differences in the relative amounts of the 52-kDa
      detected in the various treatment groups. In the medium obtained from 17 beta
      estradiol-treated cells that was serially diluted, there was an excellent linear
      correlation for the relative concentrations of the 52-kDa protein using the
      double-staining/densitometric procedure and the radioimmunoassay. These results
      indicate that the double- or silver-staining method may be a useful and rapid
      method for screening new compounds as antiestrogens in MCF-7 cells.

PMID- 1381156
TI  - Determination of amino sugars and amino acids in glycoconjugates using precolumn
      derivatization with o-phthalaldehyde.
AB  - This report examines the RP-HPLC separation of o-phthalaldehyde derivatives of
      amino acids, amino sugars, and amino sugar alcohols using either 2
      mercaptoethanol or 3-mercaptopropionic acid. A method with pmol sensitivity for
      the analysis of N-acetylamino sugars of glycoconjugates was elaborated. Upon
      hydrolysis, amino sugars are reduced with borohydride. Automated precolumn
      derivatization and chromatographic conditions for the resulting hexosaminitols
      are the same as those used for the analysis of amino acids. The method has been
      tested with as little as 2 micrograms of bovine fetuin, with a glycopeptide from
      bromelain and with an oligosaccharide after periodate oxidation.

PMID- 1381157
TI  - Application of 3-[3-(3-(trifluoromethyl)diazirin-3-yl)phenyl]-2,3-
      dihydroxypropionic acid, carbene-generating, cleavable cross-linking reagent for
      photoaffinity labeling.
AB  - N-Hydroxysuccinimide ester of 3-[3-(3-(trifluoromethyl)diazirin-3-yl)phenyl]-2,3
      dihydroxypro pionic acid was successfully tested in a ribosomal tRNA binding
      system. It is an originally designed trifluoromethyl-diazirine-based cleavable
      cross-linking reagent with a very short distance between the active points (about
      8.5 A). The reagent was coupled to the amino acid amino group of Phe-tRNAPhe to
      obtain a photoactivatable analog of peptidyl-tRNA. This analog was bound to
      ribosomes and the complex was irradiated with uv light. After isolation, the
      cross-linked product was cleft by periodate treatment to reveal the properties of
      the new reagent.

PMID- 1381160
TI  - Carotid artery resection for head and neck cancer.
AB  - Occasionally, the head and neck surgeon encounters a patient whose malignancy
      involves the carotid artery. In these patients, curative or palliative surgery
      may require excision of the common or the internal carotid artery. However, the
      high complication and death rates dissuade many surgeons from undertaking carotid
      artery resection. This study reviews the outcomes in 20 patients treated between
      1979 and 1985 at the Department of Otolaryngology-Head and Neck Surgery, The
      University of Iowa Hospitals and Clinics, with resection of the carotid artery
      for head and neck cancer. The carotid artery was electively resected in 16
      patients, while 4 patients underwent emergent carotid artery ligation. In the
      group of patients studied the stroke rate was 25%, the death rate 20%, and the
      combined stroke and death rate 30%. Of the patients who survived the procedure,
      all but 1 died of complications caused by tumor recurrence. These results are
      discussed, and compared with results from other studies.

PMID- 1381161
TI  - [Treatment of prostatic adenomas].

PMID- 1381159
TI  - Use of hypertonic saline/dextran versus lactated Ringer's solution as a
      resuscitation fluid after uncontrolled aortic hemorrhage in anesthetized swine.
AB  - STUDY OBJECTIVE: We tested the hypothesis that following aortotomy,
      administration of hypertonic saline/dextran increases hemorrhage and mortality.
      We also compared hypertonic saline/dextran with the standard therapy of
      attempting to replace three times the amount of lost blood with lactated Ringer's
      solution. DESIGN: In this model of uncontrolled arterial hemorrhage resulting
      from aortotomy, 24 anesthetized Yorkshire swine underwent splenectomy, stainless
      steel wire placement in the infrarenal aorta, and instrumentation with Swan-Ganz
      and carotid artery catheters. The wire was pulled, producing a 5-mm aortotomy and
      spontaneous intraperitoneal hemorrhage. INTERVENTIONS: The animals were randomly
      assigned to one of three study groups: control; hypertonic saline/dextran group
      in which six minutes after aortotomy a 4-mL/kg mixture of IV 7.5% NaCl and 6%
      Dextran-70 was given over one minute; or lactated Ringer's group in which six
      minutes after aortotomy 80 mL/kg IV lactated Ringer's was given over nine
      minutes. MEASUREMENTS AND MAIN RESULTS: The volume of hemorrhage and the
      mortality rate in hypertonic saline/dextran-treated animals were significantly
      greater than in the nonresuscitated controls (1,340 +/- 230 mL versus 783 +/- 85
      mL and five of eight versus zero of eight, respectively; P less than .05).
      Although the mortality rate in the lactated Ringer's group was not significantly
      different from the hypertonic saline/dextran group, survival time was
      significantly shorter than in the hypertonic saline/dextran group. CONCLUSION: In
      this model of uncontrolled hemorrhage, immediate IV administration of hypertonic
      saline/dextran significantly increased hemorrhage volume and mortality. However,
      the accentuation of hemorrhage and reduction in survival were not as great as
      that produced by the standard practice of attempting to replace the lost blood
      with three times that volume of lactated Ringer's.

PMID- 1381158
TI  - The development of substance P-like immunoreactivity in the goldfish brain.
AB  - The development of substance P-like immunoreactivity (SPLI) in the goldfish brain
      was studied by means of the indirect peroxidase-antiperoxidase technique and an
      antibody to substance P. By 80 h after fertilization, the first SPLI-cell bodies
      appear in the ventricular zone of the future diencephalon and the first SPLI
      fibers appear in the olfactory bulbs. Two days after hatching (which occurs at
      100 h after fertilization), SPLI fibers connecting the olfactory bulbs and
      hypothalamus are seen. In the optic tectum SPLI-fibers appear for the first time
      5 days after hatching. In the brain stem, SPLI-cell bodies appear in juvenile
      animals 40 days after hatching. The highest number and intensity of SPLI-cell
      bodies and fibers are found in the area postrema. SPLI-cell bodies are also seen
      in the gustatory nucleus, nucleus ambiguous, reticular formation of the medulla,
      dorsal motor nucleus of the vagus and commissural nucleus of Cajal. The
      significant information gained from the present study is: 1. The rostro-caudal
      sequence in which the SPLI appears in the developing nuclei of the goldfish brain
      2. The reduction of SPLI-cell bodies in some nuclei with age Thus, in the brain
      stem, SPLI-cell bodies that were labeled in juvenile goldfish were not seen in
      adults. This might be due to changes in the rate of axonal transport, changes of
      the SP phenotype during development or cell death. The developmental sequence and
      relative timing in which SPLI-cell bodies appear in the goldfish, rat and mice
      are similar.

PMID- 1381162
TI  - [Current therapies of benign prostatic hypertrophy. Can the new medical
      treatments replace endoscopic resection?].
AB  - There has been a renewed interest in benign prostatic hypertrophy over the last
      two years due to the development of new therapeutic modalities. A recent
      consensus conference was organized by the World Health Organization (WHO) in
      Paris in July 1991, at which conventional treatment by transurethral resection
      was compared with new methods. An updated review is made of the basic concepts
      concerning BPH and the indications, technique and results of the various
      treatments: drug treatment by alpha-blockers, hormones, other instrumental
      treatments: cryotherapy, bladder neck incision, metal stent, hyperthermia.
      Transurethral resection will be studied in detail: technique, results. The
      respective indications for these various modalities are discussed.

PMID- 1381163
TI  - [Long-term results of treatment of benign prostatic hypertrophy by trans-rectal
      prostatic hyperthermia].
AB  - From November 1987, 250 patients with symptomatic benign prostatic hyperplasia
      underwent transrectal prostatic hyperthermia. Forty-six patients had an
      indwelling catheter while 204 patients were obstructed but could still void
      spontaneously. Hyperthermia was administered in 5 or 10 sixty-minute sessions,
      with a calculated intraprostatic temperature of 42.5 or 43 degrees C. At the two
      year follow-up, residual urine volume was significantly decreased while peak flow
      rate, maximum flow nomogram and subjective symptoms were only slightly improved,
      i.e. patients were still obstructed postoperatively. Transrectal prostatic
      hyperthermia cannot be considered as a first choice therapy for symptomatic
      benign hyperplasia but it can be offered only to carefully selected patients who
      cannot undergo any alternative therapeutic procedure.

PMID- 1381164
TI  - [The alpha blockers].
AB  - Because the bladder neck contains a large number of alpha-adrenergic receptors,
      use of alpha-blockers to facilitate micturition in early benign prostatic
      hypertrophy has been advocated. Effects on micturition and urinary flow were
      fairly favorable. No adverse effects were recorded. The effect of therapy was
      transient and slightly greater than the effect of the placebo.

PMID- 1381165
TI  - [Current role of cryosurgery in benign prostatic hypertrophy compared to recent
      minimally invasive methods].
AB  - The authors review results of 20 years of cryosurgery for benign prostatic
      hypertrophy based on 992 cases treated by this method. In particular, they
      compare the 500 more recent cases of cryocauterisation with the new minimally
      invasive techniques proposed:balloon dilatation, prostatic stent, thermotherapy,
      hyperthermia, medical treatment with a 5-alpha-reductase. A study of the cost of
      these treatments with similar performances places cryosurgery in a good position.
      It covers the largest range of therapeutic indications with the fewest
      contraindications in high-risk patients. Good long-term objective results were
      observed. In their current state of application, thermotherapy and hyperthermia
      are essentially palliative modalities.

PMID- 1381166
TI  - [History of benign prostatic hypertrophy].

PMID- 1381167
TI  - Shared T-cell receptor gene usage in experimental allergic neuritis and
      encephalomyelitis.
AB  - Experimental allergic neuritis, an autoimmune disease of the peripheral nervous
      system, is a model for human Guillain-Barre syndrome. Experimental allergic
      neuritis is mediated by CD4+ T cells reactive with myelin P2 protein. We
      demonstrate that these T cells use the same members of T-cell receptor V gene
      families for both their alpha (V alpha 2) and beta (V beta 8) chains as T cells
      that cause experimental allergic encephalomyelitis, an autoimmune disease of the
      central nervous system. Furthermore, these T cells appear to be idiotypically
      related. Therefore, completely different T-cell lines with different antigen
      specificities, producing entirely different diseases, share common T-cell
      receptors.

PMID- 1381168
TI  - Sensory neuropathy associated with monoclonal immunoglobulin M to GD1b
      ganglioside.
AB  - A 67-year-old woman with a sensory polyneuropathy was shown to have a serum
      monoclonal immunoglobulin M lambda antibody with a titer of 1:10,000 toward GD1b
      ganglioside. The immunoglobulin M also reacted with some other gangliosides
      containing disialosyl groups such as GD2, GD3, and GQ1b, but it did not react
      with GM1, LM1, or GD1a. The principal reactive ganglioside in human cauda equina
      was GD1b.

PMID- 1381169
TI  - Monoclonal gammopathy and neuropathy.

PMID- 1381170
TI  - Monoclonal gammopathy and neuropathy.

PMID- 1381171
TI  - Degradation of Giardia lamblia cysts in mixed human and swine wastes.
AB  - This study was conducted to determine the persistence of Giardia lamblia cysts in
      mixed septic tank effluent and swine manure slurry and to correlate fluorescein
      diacetate-propidium iodide staining of G. lamblia cysts with their morphology
      under low-voltage scanning electron microscopy. Under field conditions, G.
      lamblia cysts were degraded more rapidly in the mixed waste than in the control
      Dulbecco's phosphate-buffered saline (PBS). For total and viable cysts, the mixed
      waste had D values (time for a 90% reduction in number of cysts) of 18.3 and 15.5
      days, and the Dulbecco's PBS control had D values of 41.6 and 26.8 days. The
      rates of cyst degradation in septic tank effluent and in Dulbecco's PBS were
      similar. Increasing the proportion of swine manure slurry in the mixed waste
      favored degradation of the parasite. These results indicate that the mixed waste
      treatment was the predominant factor affecting the cyst persistence and that it
      was swine manure slurry that played the role of degrading the parasite.
      Visualization of viable and nonviable Giardia cysts with low-voltage scanning
      electron microscopy revealed an excellent correlation between the viability of
      the cysts determined by fluorescein diacetate-propidium iodide staining and their
      electron microscopic morphology.

PMID- 1381172
TI  - Utilization of 3-chloro-2-methylbenzoic acid by Pseudomonas cepacia MB2 through
      the meta fission pathway.
AB  - Pseudomonas cepacia MB2 grew on 3-chloro-2-methylbenzoate as a sole carbon source
      by metabolism through the meta fission pathway with the subsequent liberation of
      chloride. meta pyrocatechase activity in cell extracts was induced strongly by 3
      chloro-2-methylbenzoate, but not by nongrowth analogs 4- or 5-chloro-2
      methylbenzoate. Although rapid turnover of metabolites precluded direct
      identification, a mutant strain MB2-G5 lacking meta pyrocatechase activity
      produced 4-chloro-3-methylcatechol when incubated with 3-chloro-2-methylbenzoate.
      The catecholic product, confirmed by nuclear magnetic resonance and mass spectral
      analyses, produced a transient meta fission product (lambda max = 391 nm) from
      cell extracts of the wild-type MB2 strain. Further confirmation of meta
      pyrocatechase activity was noted by conversion of 4-chlorocatechol to 2-hydroxy-5
      chloromuconic semialdehyde, which was not further metabolized. In contrast to 3
      chlorocatechol, which was not metabolized and is known to generate suicidal
      products, 4-chlorocatechols do not generate acyl halides. Thus, further
      metabolism of the ring fission products is governed in strain MB2 by their
      suitability as substrates for the hydrolase.

PMID- 1381173
TI  - Rapid in situ hybridization technique using 16S rRNA segments for detecting and
      differentiating the closely related gram-positive organisms Bacillus polymyxa and
      Bacillus macerans.
AB  - A rapid, sensitive, inexpensive in situ hybridization technique, using 30-mer 16S
      rRNA probes, can specifically differentiate two closely related Bacillus spp., B.
      polymyxa and B. macerans. The 16S rRNA probes were labeled with a rhodamine
      derivative (Texas Red), and quantitative fluorescence measurements were made on
      individual bacterial cells. The microscopic fields analyzed were selected by
      phase-contrast microscopy, and the fluorescence imaging analyses were performed
      on 16 to 67 individual cells. The labeled 16S rRNA probe, POL, whose sequence was
      a 100% match with B. polymyxa 16S rRNA but only a 60% match with B. macerans 16S
      rRNA, gave quantitative fluorescence ratio measurements that were 34.8-fold
      higher for B. polymyxa cells than for B. macerans cells. Conversely, the labeled
      probe, MAC, which matched B. polymyxa 16S rRNA in 86.6% of its positions and B.
      macerans 16S rRNA in 100% of its positions, gave quantitative fluorescence
      measurements that were 59.3-fold higher in B. macerans cells than in B. polymyxa
      cells. Control probes, whose 16S rRNA sequence segment (P-M) was present in both
      B. polymyxa and B. macerans as well as a panprokaryotic probe (16S), having a
      100% match with all known bacteria, hybridized equally well with both organisms.
      These latter hybridizations generated very high fluorescence signals, but their
      comparative fluorescence ratios (the differences between two organisms) were low.
      The control paneukaryotic probe (28S), which had less than 30% identity for both
      B. macerans and B. polymyxa, did not hybridize with either organism.

PMID- 1381175
TI  - [Interferon-inducing activity of hydroxybenzylamine derivative].
AB  - Interferon-inducing activity of the interferon inductor savrats, an
      oxybenzylamine derivative of was studied. It was shown on experimental animals
      that along with its low toxicity, savrats had a high interferon inducing
      capacity. There were early and late peaks of interferon production (4-8 and 48-96
      hours later, respectively) depending on the route of the inductor administration.
      It was noted that for optimization of the schemes for using interferon inductors,
      careful choosing of the drug pairs participating in the induction and employment
      of various routes for administration of the same drug are required.

PMID- 1381176
TI  - Immunohistochemical study of nerve fibres with substance P- or calcitonin gene
      related peptide-like immunoreactivity in the junctional epithelium of developing
      rats.
AB  - The beginning of innervation in the junctional epithelium of maxillary first
      molars was examined in gingival tissues from 19 to 32-day-old rats. Substance P-
      or calcitonin gene-related peptide (CGRP)-like immunoreactivity was demonstrated
      by the avidin-biotin peroxidase complex method. In 19-day-old rats, nerve fibres
      with substance P- or CGRP-like immunoreactivity were seen in the connective
      tissue and oral epithelium, but not in the reduced enamel epithelium, which would
      be transformed into the junctional epithelium. In 21-day-old rats, the fibres
      with substance P- or CGRP-like immunoreactivity formed a plexus in the oral
      sulcular epithelium and thin varicose fibres were seen for the first time
      entering the adjacent reduced enamel epithelium. These fibres also penetrated the
      middle portion of the reduced enamel epithelium, but did not reach the cuboidal
      reduced ameloblasts. More nerve fibres had CGRP-like immunoreactivity than
      substance P-like immunoreactivity. In 23-day-old rats, many fibres with both
      immunoreactivities were seen in the basal layers of the junctional epithelium,
      but only a few were seen in its superficial layers. In 28-32-day-old rats,
      numerous fibres with both immunoreactivities were distributed in the whole
      junctional epithelium and showed a similar pattern of innervation. For all
      immunoreactive fibres, the density in the middle portion in the junctional
      epithelium was the highest. The nerve plexus was formed in the basal layers and
      some fibres with a varicose appearance were found in the superficial layers.

PMID- 1381174
TI  - Genus- and species-specific identification of mycoplasmas by 16S rRNA
      amplification.
AB  - Systematic computer alignment of mycoplasmal 16S rRNA sequences allowed the
      identification of variable regions with both genus- and species-specific
      sequences. Species-specific sequences of Mycoplasma collis were elucidated by
      asymmetric amplification and dideoxynucleotide sequencing of variable regions,
      using primers complementary to conserved regions of 16S rRNA. Primers selected
      for Mycoplasma pneumoniae, M. hominis, M. fermentans, Ureaplasma urealyticum, M.
      pulmonis, M. arthritidis, M. neurolyticum, M. muris, and M. collis proved to be
      species specific in the polymerase chain reaction. The genus-specific primers
      reacted with all mycoplasmal species investigated as well as with members of the
      genera Ureaplasma, Spiroplasma, and Acholeplasma. No cross-reaction was observed
      with members of the closely related genera Streptococcus, Lactobacillus,
      Bacillus, and Clostridium or with any other microorganism tested. On the basis of
      the high copy number of rRNA, a highly sensitive polymerase chain reaction assay
      was developed in which the nucleic acid content equivalent to a single organism
      could be detected.

PMID- 1381177
TI  - Pancreatic juice cytology for monitoring pancreatic grafts in the early
      postoperative period.
AB  - Thirty-one pancreas transplant recipients were monitored by pancreatic juice
      cytology in the early postoperative period. An increase in the total amount of
      cells and, in particular, signs of immunoactivation with the appearance of two or
      more blast-transformed cells per specimen were taken as evidence of acute
      rejection. According to these criteria a total of 38 rejection episodes were
      diagnosed. The first positive cytology appeared after 9 days (mean) and lasted
      for 2 days (mean). Immunocytochemical analysis of the juice showed increased
      amounts of CD3+ cells during rejection. When rejection occurred during
      prophylaxis with antithymocyte globulin, neutrophils were preponderant in the
      pancreatic juice while during OKT-3 prophylaxis a high percentage of monocytes
      was a characteristic finding. Antirejection treatment was started when the
      cytology became positive and all rejection episodes except one were reversed. A
      decrease in the pancreatic juice amylase activity occurred in 66% of the
      rejection episodes, but in only 5 of the 38 episodes was the decrease highly
      significant. No correlation was found between graft rejection and volume
      excretion of pancreatic juice. There were no persistent or characteristic changes
      in serum amylase or peripheral white blood cell count at the time of rejection.
      Graft pancreatitis was diagnosed cytologically in 7 patients, in 5 of whom the
      grafts were eventually lost.

PMID- 1381178
TI  - Challenges and choices.

PMID- 1381179
TI  - Relationship between gonadotrophin subunit gene expression, gonadotrophin
      releasing hormone receptor content and pituitary and plasma gonadotrophin
      concentrations during the rebound release of FSH after treatment of ewes with
      bovine follicular fluid during the luteal phase of the cycle.
AB  - The modulation of FSH secretion at the beginning and middle of the follicular
      phase of the cycle represents the key event in the growth and selection of the
      preovulatory follicle. However, the mechanisms that operate within the pituitary
      gland to control the increased release of FSH and its subsequent inhibition in
      vivo remain unclear. Treatment of ewes with bovine follicular fluid (bFF) during
      the luteal phase has been previously shown to suppress the plasma concentrations
      of FSH and, following cessation of treatment on day 11, a rebound release of FSH
      occurs on days 12 and 13. When luteal regression is induced on day 12, this
      hypersecretion of FSH results in an increase in follicle growth and ovulation
      rate. To investigate the mechanisms involved in the control of FSH secretion,
      ewes were treated with twice daily s.c. injections of 5 ml bFF on days 3-11 of
      the oestrous cycle and luteal regression was induced on day 12 with prostaglandin
      (PG). The treated ewes and their controls were then killed on day 11 (luteal), or
      16 or 32 h after PG and their pituitaries removed and halved. One half was
      analysed for gonadotrophin and gonadotrophin-releasing hormone (GnRH) receptor
      content. Total pituitary RNA was extracted from the other half and subjected to
      Northern analysis using probes for FSH-beta, LH-beta and common alpha subunit.
      Frequent blood samples were taken and assayed for gonadotrophins. FSH secretion
      was significantly (P less than 0.01) reduced during bFF treatment throughout the
      luteal phase and then significantly (P less than 0.01) increased after cessation
      of treatment, with maximum secretion being reached 18-22h after PG, and then
      declining towards control values by 32h after PG. A similar pattern of LH
      secretion was seen after bFF treatment. Pituitary FSH content was significantly
      (P less than 0.05) reduced by bFF treatment at all stages of the cycle. No
      difference in the pituitary LH content was seen. The increase in GnRH receptor
      content after PG in the controls was delayed in the treated animals. Analysis of
      pituitary mRNA levels revealed that bFF treatment significantly (P less than
      0.01) reduced FSH-beta mRNA levels in the luteal phase. Increased levels of FSH
      beta, LH-beta and alpha subunit mRNA were seen 16h after PG in the bFF-treated
      animals, at the time when FSH and LH secretion from the pituitary was near
      maximum.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1381180
TI  - LH receptor RNA and protein levels after hormonal treatment of porcine granulosa
      cells in primary culture.
AB  - Granulosa cells were prepared from small follicles (less than 3 mm) from the
      ovaries of 5-month-old gilts. They were cultured in plastic dishes coated with a
      synthetic adhesion peptide in a chemically defined medium supplemented with 2%
      serum substitute. After 3 days of culture, the cells reached confluence and
      expression of the LH receptor could be stimulated in a hormonally defined medium.
      LH receptor RNAs were estimated by autoradiography using Northern blots and dot
      blots of total cell RNA. LH receptor RNAs were hybridized with a homologous 32P
      labelled random-primed DNA probe. The LH receptor was measured using 125I
      labelled human chorionic gonadotrophin (hCG) as tracer. Northern blots of LH
      receptor RNAs revealed a predominant signal of 4.4 kb and two less-intense
      hybridization bands of 7.5 and 1.9 kb. The 4.4 kb band was used for
      quantification of LH receptor RNAs because it was the most intense and may be
      attributed to the full-length messenger RNA. In these conditions, after 72 h
      stimulation, FSH (0.6 nM), insulin (5 micrograms/ml), oestradiol (30 nM) and
      deoxycorticosterone (0.3 nM) yielded high LH receptor RNA levels (eight times
      unstimulated cell level), while dibutyryl cyclic AMP (1 mM), cortisol (5.4 nM),
      thyroxine (100 nM) and epidermal growth factor (16 pM) gave low LH receptor RNA
      levels (one to five times). However, the respective amounts of the receptor RNA
      did not give yield to the same proportion of LH receptor for every factor,
      indicating some post-transcriptional regulations. The kinetic study of the
      production of the LH receptor obtained in a defined medium supplemented with FSH,
      oestradiol and insulin showed that the receptor appeared after 48 h of
      stimulation and reached a maximum of about 7000 receptors per cell at 72 h. The
      three hybridization bands on Northern blots evolved in parallel and appeared as
      early as 24 h. They were at maximal level from 24 to 48 h of stimulation. When
      the granulosa cells were pulse-treated for 2 h with cycloheximide (10
      micrograms/ml), they exhibited a transient rise in LH receptor RNA content which
      was followed by a delayed receptor increase especially at 72 h of stimulation.
      Taken together, these results indicate that the LH receptor in primary culture of
      granulosa cells seems to be regulated by different physiological factors both at
      the transcriptional and the translational levels.

PMID- 1381181
TI  - Differential expression of the insulin-like growth factor binding proteins in
      spontaneously diabetic rats.
AB  - Diabetes-induced growth retardation in the rodent is associated with both reduced
      circulating insulin-like growth factor-I (IGF-I) and enhanced levels of
      inhibitors of somatomedin activity. IGF-binding proteins (IGFBPs) are present in
      the circulation and tissue fluids and are believed to modulate the actions of IGF
      I. Since elevated concentrations of the IGFBPs may contribute to the enhanced
      somatomedin-inhibitor activity observed in serum from diabetic animals, we have
      examined the amounts of hepatic IGFBP-1, -2, -3 and -4 mRNA in the spontaneously
      diabetic BioBreeding/Worcester rat. The study used two types of diabetic animal:
      mildly diabetic animals, which received suboptimal insulin treatment (0.5-1
      U/day) and diabetic animals, which received intensive insulin treatment (3-6
      U/day). A significant increase in the amount of IGFBP-1 and IGFBP-2 mRNA was seen
      1 month and 3 months after the onset of diabetes. Intensive insulin treatment for
      3 weeks normalized the amount of IGFBP-1 mRNA in diabetic rats and resulted in a
      decrease in IGFBP-2 mRNA. In contrast to the increase in IGFBP-1 and IGFBP-2
      mRNA, a significant decrease in IGFBP-3 mRNA was seen in diabetic rats (54.6% of
      control, P less than 0.0005 and 64.6% of control, P less than 0.005 for 1 and 3
      months respectively) and intensive insulin treatment for 3 weeks did not restore
      the IGFBP-3 mRNA level in diabetic rats. No significant difference in IGFBP-4
      mRNA levels was seen in diabetic compared with non-diabetic rats. When serum was
      analysed by ligand blotting the major finding was a reduction in the 39-42 kDa
      binding protein. No increase in 29-30 kDa IGFBP in the serum was detected in the
      diabetic rats. From these studies we conclude that the major change in IGFBPs in
      mildly hyperglycaemic spontaneously diabetic rats is a decrease in IGFBP-3. The
      changes in hepatic IGFBP-1 and -2 mRNA do not appear to be of sufficient
      magnitude to result in an increase in serum concentrations of these binding
      proteins.

PMID- 1381182
TI  - The characterization and expression of ovine insulin-like growth factor-binding
      protein-2.
AB  - We have isolated an ovine insulin-like growth factor-binding protein-2 (IGFBP-2)
      cDNA from an adult sheep cDNA library, to determine the structure of ovine IGFBP
      2 and to examine the pattern of IGFBP-2 gene expression in adult sheep tissues.
      This cDNA had 81, 96 and 87% identity with the rat, bovine and human sequences
      respectively. The deduced amino acid sequence of the ovine IGFBP-2 showed 86, 95
      and 85% homology with the rat, bovine and human peptide sequences respectively.
      The ovine IGFBP-2 cDNA encoded a precursor protein of 317 amino acids which
      comprised a 33 residue hydrophobic leader sequence and a 284 residue, 30.9 kDa,
      mature peptide. The 18 cysteine residues, which are a characteristic feature of
      IGFBPs, were conserved. Also, an Arg-Gly-Asp (RGD) sequence near the C terminus
      was present. A single transcript of approximately 1.5 kb was expressed in
      abundance in selected tissues of an adult sheep, namely liver, kidney, adrenal,
      pituitary and choroid plexus. Southern blot analysis of ovine genomic DNA with
      the cDNA probe demonstrated that IGFBP-2 is encoded by a single gene. These
      findings indicate that the ovine IGFBP-2 protein is similar to that in other
      species and that, in the adult, the mRNA is expressed only in selected tissues.

PMID- 1381183
TI  - Macromolecular prodrugs. XX. Factors influencing model dextranase-mediated
      depolymerization of dextran derivatives in vitro.
AB  - Endo-dextranase-mediated depolymerization of dextran and dextran derivatives
      under various experimental conditions in vitro was determined. By a simultaneous
      determination of Mn and MW of dextrans treated with the enzyme in aqueous buffer,
      an initial increase of the polydispersity of the polysaccharide sample was
      observed, indicating that dextranase cleaved the dextran molecules into chains
      which differed significantly in length. A pH optimum of 5 for the enzyme action
      was found. However, in the pH range 5-8, which prevails in the colon, the initial
      depolymerization rates differed by a factor of less than 2. Dextranase treatment
      of a dextran sample resulted in a constant increase of the concentration of
      terminal reducing glucose residues per time unit suggesting, that the initial
      depolymerization reaction followed zero-order kinetics. For degrees of
      substitution below 12 the efficacy of dextranase fragmentation of dextran
      conjugates decreased almost linearly with increasing DS. The chemical nature of
      the attached drug did not significantly affect the depolymerization rates.
      Maximally depolymerized dextran derivatives were obtained by the combined action
      of dextranase and various alpha-glucosidases. Treatment of such solutions with:
      a) model esterases b) 80% plasma and c) 20% liver homogenate did not give rise to
      an acceleration of the initial drug regeneration, as compared to identical
      experiments carried out in pure buffer solution (pH 7.4 and 37 degrees C).

PMID- 1381184
TI  - Studies on human porin. VII. The channel properties of the human B-lymphocyte
      membrane-derived "Porin 31HL" are similar to those of mitochondrial porins.
AB  - Porin 31HL was isolated and purified from total membrane preparations of a human
      B-lymphocyte cell line. The protein showed a single band of apparent molecular
      mass 31 kDa on SDS-PAGE. Reconstitution of the protein into artificial lipid
      bilayer membranes defines its function as a channel-forming protein. The
      distribution of single-channel conductances had two maxima of 2.4 and 4.3 nS in
      1M KCl. The channel formed by Porin 31HL of human B-lymphocytes was found to be
      voltage-dependent and switched to ion-permeable substates at membrane voltage
      larger than 20mV. In the open state the pore exhibited the characteristics of a
      general diffusion pore because the mobility sequence of the ions inside the pore
      was similar to that in the bulk aqueous phase. The effective diameter was
      estimated to be about 1.7 nm. The properties of the low conductance state of the
      channel were studied in detail. In this state the pore favored the passage of
      cations, in contrast to the open state which favored anions slightly. Monoclonal
      antibodies against the N-terminal end of Porin 31HL blocked its reconstitution
      but had otherwise no influence on the channel properties. This result suggested
      that the amphipathic alpha-helical structure at the N-terminal end is probably
      not involved in channel gating. The channel-forming properties of Porin 31HL were
      compared to those of porins isolated from mitochondrial outer membranes and to
      those of the "maxi chloride channel" observed in the cytoplasmic membrane of
      several eukaryotic cells.

PMID- 1381185
TI  - Induction and detection of anti-peptide antibody specificity is critically
      affected by the mode of hapten presentation.
AB  - C-Terminal cholecystokinin (CCK)-peptides of increasing chain lengths were all
      linked at their N-termini to the single surface-exposed cysteine residue 107 of
      yeast iso-1-cytochrome c by the maleimide/thiol reaction. The resulting
      CCK/cytochrome 1:1 conjugates with the haptenic peptides in the identical protein
      environment were used to immunize outbred guinea pigs in order to assess the
      critical size of CCK peptides required for the expression of a CCK-specific
      epitope and the induction of antibodies not crossreacting with the homologous
      gastrin sequence. By using standard ELISA techniques with polystyrene-adsorbed
      antigen to evaluate the specificity of the antisera, none of the conjugates were
      found to induce anti-CCK antisera not crossreacting with gastrin. However, when
      the biotinyl-CCK-antigen was immobilized by polystyrene-adsorbed avidin, i.e. via
      a procedure which assures maximum accessibility of the bound antigen, we were
      able to demonstrate that with CCK-12 and particularly CCK-13, linked through
      their N-termini to the carrier, the critical length for the expression and
      recognition of a CCK-specific epitope was reached. The related polyclonal
      antisera did not crossreact with the homologous gastrin in the modified ELISA.

PMID- 1381186
TI  - Quaternary structure of apolipoprotein E in solution: fluorimetric,
      chromatographic and immunochemical studies.
AB  - Self-association and stability in solution of apolipoprotein E (apoE), isolated
      from human plasma very low density lipoproteins, were studied in the nanomolar
      concentration range. Equilibrium denaturation of fluorescein-labelled apoE
      (induced by guanidine hydrochloride) was studied by measurement of fluorescence
      anisotropy, total fluorescence emission intensity, the shift in wavelength of
      maximal fluorescence emission, and gel-chromatographic behaviour. The protein
      denaturation was reversible, displayed biphasic behaviour, and was dependent on
      the apoE concentration. As measured by fluorescence anisotropy, the kinetics of
      apoE denaturation in the presence of 6M denaturant were heterogeneous, and the
      contribution of the long-lived component increased with the apoprotein
      concentration. The results are in agreement with the following scheme: Oligomer
      (in aged preparations) in equilibrium with tetramer in equilibrium with native or
      partially denatured monomer in equilibrium with fully denatured monomer. It is
      suggested that self-association of individual apoE molecules in solution is due
      to their lipid-binding domains, and leads to additional stabilization of
      apoprotein structure. Monoclonal antibody 3D12F11 of the IgG1 subclass bound with
      high affinity to apoE (Kd = 3.5 +/- 0.5 nM), and had no effect on apoprotein
      binding to heparin-Sepharose or the apoprotein-induced destabilization of
      liposomes formed from dipalmitoyl-phosphatidylcholine. This indicates that the
      epitope to the antibody is localized outside the heparin- and lipid-binding sites
      of the apoprotein molecule.

PMID- 1381187
TI  - Gene expression of the high molecular weight proteinase inhibitor alpha 2
      macroglobulin.

PMID- 1381188
TI  - Flow cytometric analysis of protease activities in vital cells.
AB  - The analysis of lysosomal proteases in cell lysates is complicated by pH
      dependent and oxidative changes of their activity and complex formation with
      cytosolic inhibitors. Therefore, new flow cytometric methods were developed for
      the intracellular measurement of protease activities in viable cells.
      Intracellular cleavage of substrates such as Z-Arg-Arg-4
      trifluoromethylcoumarinyl-7-amide to green fluorescent 7-amino-4
      trifluoromethylcoumarin (AFC) in viable neutrophils and monocytes was only
      detected following phagocytosis of Escherichia coli. A measurement of the
      cysteine or serine proteinase activities in resting human leukocytes was,
      however, not possible with AFC derivatives as the overlapping blue fluorescence
      of the substrates reduces sensitivity. Nonfluorescent bis-substituted peptide
      derivatives of rhodamine 110 (R110), which are intracellularly cleaved to green
      fluorescent mono-substituted R110 and free R110 proved to be more sensitive
      substrates. The activity of the lysosomal cysteine proteinases of human monocytes
      or rat macrophages, i.e. cathepsin B and L, was specifically measured with (Z-Arg
      Arg)2-R110, (Z-Phe-Arg)2-R110, or (Z-Ala-Arg-Arg)2-R110. Fluorescence generation
      was completely inhibited by Z-Phe-Ala-diazomethane or E-64. The serine
      proteinases of human neutrophils were analyzed with Elastase-substrates such as
      (Z-Ala-Ala)2-R110 or (Z-Ala-Ala-Ala)2-R110. Specificity was shown by inhibition
      with diisopropylfluorophosphate.

PMID- 1381189
TI  - Tumor necrosis factor regulation of endothelial cell extracellular proteolysis:
      the role of urokinase plasminogen activator.
AB  - Morphological and functional changes in the endothelial cell phenotype which may
      be central to proinflammatory processes can be elicited by tumor necrosis factor
      alpha (TNF). Recent observations have indicated that TNF can promote the
      expression, synthesis and secretion of urokinase plasminogen activator (uPA) in
      low passage human umbilical vein endothelial cells which normally synthesize
      little uPA. To further address this issue, we evaluated the ability of TNF to
      regulate: 1) PA and plasminogen activator inhibitor (PAI-1) mRNA expression and
      2) endothelial cell surface associated PA and PAI-1. TNF (100 U/ml) treatment of
      endothelial cultures induced steady state levels of uPA and PAI-1 mRNA following
      a 18 hr treatment both 6-fold and 2-fold, respectively utilizing northern
      analysis. In accord with Northern analyses, TNF stimulated a time and dose
      dependent increase in cell surface associated uPA antigen as determined by a cell
      based ELISA assay and immunofluorescence in conjunction with flow cytometry.
      Treatment of endothelial cell cultures with 100 U/ml of TNF resulted in a 3-fold
      increase in cell surface uPA antigen levels which peaked at 8 hr. In contrast, no
      changes in tissue-PA (tPA) and PAI-1 cell surface antigen expression were evident
      under analogous conditions over a 24 hr period. The TNF mediated increase in both
      uPA mRNA and cell surface uPA expression correlated with the increased ability of
      endothelial cells to invade matrix and organize into tube-like structures when
      cultured on Matrigel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381190
TI  - Induction of 2'-5' oligoadenylate synthetase during interferon treatment of
      chronic myelogenous leukemia.
AB  - Activity of the interferon-induced enzyme 2'-5' oligoadenylate synthetase (2-5
      OAS) was measured in peripheral blood mononuclear cells (PBMCs) and serum of
      patients with chronic phase Ph'-positive chronic myelogenous leukemia (CML)
      treated with interferon-alpha (IFN-alpha) (4 x 10(6) IU/m2) alone or in
      combination with 50 micrograms IFN-gamma. At the beginning of IFN therapy, marked
      elevation of 2-5 OAS titers was detected in PBMCs (pretreatment 0.03-1.62, median
      0.2; during treatment 0.8-13.14, median 4.31; 22 patients studied) and in serum
      (pretreatment 21-156 pmol/dl, median 62; during treatment 532-1740 pmol/dl,
      median 800; eight patients studied). However, 2-5 OAS titers were not related to
      clinical outcome or IFN therapy and also during IFN resistance elevated 2-5 OAS
      activity in PBMCs (median 3.45; range 1.05-13.14; 11 patients studied) were
      detected. These data argue against direct involvement of the 2-5 OAS system in
      the therapeutic effect of IFN in CML. However, 2-5 OAS titers in PBMCs or serum
      appear to be a reliable control of biologically active IFN therapy.

PMID- 1381191
TI  - The 80L5C4 epitope overlaps with the homophilic binding site of the cell adhesion
      molecule gp80 of Dictyostelium.
AB  - The monoclonal antibody (mAb) 80L5C4 is a potent inhibitor of the cell adhesion
      molecule gp80 of Dictyostelium discoideum. To map the exact location of the
      epitope recognized by mAb 80L5C4, overlapping hexapeptides were synthesized on
      plastic pins and the binding p6 mAb 80L5C4 to these peptides was monitored by
      enzyme-linked immunosorbent assay. The 80L5C4 epitope is mapped to a single
      hexapeptide sequence GYKLNV, which shares five amino acid residues with the
      octapeptide sequence YKLNVNDS involved in gp80 homophilic binding. Analogue
      studies indicate that the hydrophobic residues within this sequence are crucial
      for antigen recognition.

PMID- 1381192
TI  - Modifications of the guanidine hydrochloride procedure for the extraction of RNA:
      isolation from a variety of tissues and adherent/nonadherent cell types.
AB  - In a previous report dealing with the guanidine hydrochloride protocol for the
      extraction of RNA from mouse peritoneal macrophages, we identified a major source
      of RNA-degrading activity and showed that its removal early in the extraction
      procedure resulted in a more dependable method for the recovery of high-quality
      RNA. This report extends these findings and demonstrates the general
      applicability of the technique to a variety of fresh or frozen adherent cell
      types, cell suspensions and tissues, further highlighting stages at which
      degradation is most likely to occur and how to avoid a variety of pitfalls
      associated with the extraction procedure.

PMID- 1381193
TI  - Western blots using stained protein gels.
AB  - A general method is described for the electrophoretic transfer of proteins from
      stained gels to membranes and subsequent Western detection of specific proteins
      on the stained membranes. Proteins are separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and the gels are stained using either of two
      different methods followed by electrophoretic transfer to nitrocellulose or
      Immobilon-P membranes. The transferred proteins remain stained during
      immunodetection, providing a set of background markers for protein location and
      size determination.

PMID- 1381194
TI  - A rapid procedure for isolating RNA from small-scale Bacillus cultures.

PMID- 1381195
TI  - A simplified, single tube, single buffer system for RNA-PCR.

PMID- 1381196
TI  - RNA abundance measured by a lysate RNase protection assay.
AB  - We describe a sensitive ribonuclease protection assay that we have used to
      measure the amount of interferon-beta RNA directly in lysates of human cells.
      Cell lysates were prepared in concentrated guanidine thiocyanate. Molecular
      hybridization with RNA probes was then performed directly in crude cell lysate,
      and native RNase-resistant duplexes were characterized by polyacrylamide gel
      electrophoresis. Comparison of interferon-beta RNA abundance by quantitative
      solution hybridization and lysate RNase protection showed that lysate RNase
      protection was highly quantitative. A high degree of reproducibility of the
      method was determined with a glyceraldehyde-3-phosphate dehydrogenase
      "housekeeping" gene probe. Sensitivity of lysate RNase protection was determined
      using both induced interferon-beta RNA and synthetic human endogenous reverse
      transcriptase RNA as target. The lysate RNase protection method was able to
      measure as few as 10(4)-10(5) RNA molecules.

PMID- 1381197
TI  - Comparison of embryonic developmental competence of mouse oocytes grown with and
      without serum.
AB  - The first objective of this study was to determine whether oocyte growth in serum
      free medium affects the solubility of the zona pellucida to alpha-chymotrypsin
      digestion, which is an index of zona pellucida "hardening" and reflects the
      potential penetrability of the zona pellucida by sperm. Oocyte-granulosa cell
      complexes were isolated from the preantral follicles of 12-day-old mice and
      cultured for 10 days in medium containing 5% fetal bovine serum (FBS) or in serum
      free medium. The zonae pellucidae of oocytes grown in serum-free medium were four
      times as hard as freshly isolated germinal vesicle (GV)-stage oocytes grown in
      vivo or oocytes grown in vitro in FBS-containing medium. The hardening of the
      zonae pellucidae of oocytes grown in serum-free medium was prevented by addition
      of fetuin. The second objective was to compare the competence to undergo
      embryogenesis of oocytes that grew in serum-free vs. FBS-containing medium.
      Approximately 70% of the oocytes underwent maturation regardless of whether the
      medium was serum-free or contained FBS. Of the mature ova grown in medium
      containing FBS, 53% cleaved to the two-cell stage after insemination compared
      with only 6% of the ova grown in serum-free medium. Addition of fetuin to the
      serum-free medium used for oocyte growth increased the frequency of cleavage to
      the two-cell stage. Of the embryos derived from oocytes that grew in FBS
      containing medium, 70% completed the two-cell stage to blastocyst
      transition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381198
TI  - Human zona pellucida during in vitro fertilization: an ultrastructural study
      using saponin, ruthenium red, and osmium-thiocarbohydrazide.
AB  - The human zona pellucida (ZP) and its changes during in vitro fertilization in
      oocytes at different maturational stages and polypronuclear ova at one- to four
      cells stages were studied by transmission electron microscopy (TEM) and
      correlative scanning electron microscopy (SEM). To define the microstructure of
      the ZP, its amorphous masking material was removed using a detergent (saponin),
      and its structural glycoproteins were stabilized with a cationic dye, ruthenium
      red, followed by osmium-thiocarbohydrazide treatment. These methods allowed in
      all samples the clear visualization of variously arranged networks of filaments
      composing the outer and inner surfaces of the ZP. These filaments were straight
      or curved, 0.1-0.4 microns in length and 10-14 nm thick as seen via TEM or 22-28
      nm thick as seen via SEM (the difference in thickness was due to the presence of
      the metal coating for SEM). The filament arrangement was remarkably different
      between the inner and outer surfaces of the ZP and among the various stages
      studied. The filaments of the outer surface of the ZP were basically arranged in
      "large" and "tight" meshed networks. Mature oocytes and fertilized
      (polypronuclear) ova had a regular alternating pattern of wide and tight meshed
      networks of filaments. On the other hand, immature and atretic oocytes displayed
      almost exclusively a tight meshed network of filaments. The inner surface
      filaments of the ZP of unfertilized oocytes at any stage were arranged in
      repetitive structures characterized by numerous short and straight filaments
      anastomosing with each other and sometimes forming at the intersections small,
      rounded structures. After fertilization, the inner surface of the ZP displayed
      numerous areas where filaments fused together. Collectively, these data clearly
      reveal that oocyte maturation and fertilization in humans are accompanied by
      changes of ZP filaments arrangement, which may be relevant in the processes of
      binding, penetration, and selection of spermatozoa.

PMID- 1381199
TI  - Identification of a small epitope in domain Ib of Pseudomonas aeruginosa exotoxin
      A that elicits enzyme-neutralizing antibodies.
AB  - A peptide corresponding to amino acids 392-404 of the amino acid sequence of
      Pseudomonas aeruginosa exotoxin A (the last 13 amino acids of domain Ib) was
      synthesized and coupled to thyroglobulin. The conjugate induced an antiserum in
      rabbits with high antibody titer against native toxin as measured by ELISA, and
      this antiserum was highly efficient in inhibiting the ADP-ribosyltransferase
      activity of exotoxin A. These data corroborate the potential importance of amino
      acids 400-404 in the enzymatic mechanism of exotoxin A.

PMID- 1381200
TI  - Uridine and cytidine nucleotide synthesis in renal hypertrophy: biochemical
      differences in response to the growth stimulus of diabetes and unilateral
      nephrectomy.
AB  - The effects of unilateral nephrectomy (UN) and streptozotocin (STZ) diabetes on
      the activities of enzymes involved in uridine and cytidine synthesis in early
      renal growth (3-14 days after stimulus to growth) have been compared.
      Measurements were also made of glucose-6-phosphate dehydrogenase (G6PDH) and 6
      phosphogluconate dehydrogenase (6PGDH) and of glucose 6-phosphate (G6P), UDP
      glucose, and glycogen, in relation to phosphoribosyl pyrophosphate,
      ribonucleotide, and complex carbohydrate formation. There were striking
      differences in the activities of CTP synthetase, G6PDH, and 6PGDH in the two
      conditions, with a three-fold increase in all three enzymes at 3 and 5 days and a
      two-fold increase above basal values at 14 days of STZ diabetes. The UN group
      showed no significant change in CTP synthetase at any stage and the activity of
      G6PDH and 6PGDH only kept pace with renal growth. Changes in routes of uridine
      synthesis were less marked, with a more rapid rise in carbamoyl-phosphate
      synthetase (glutamine) and a lesser response of dihydroorotate dehydrogenase in
      the UN relative to the STZ-diabetic groups. The enzymes of complex II and of
      uracil phosphoribosyltransferase showed essentially similar patterns during renal
      hypertrophy in UN and STZ diabetes. The parallel increase in CTP synthetase,
      G6PDH, and 6PGDH in the kidney in diabetes, also known to increase in growth
      situations in hepatomas and in renal tumors, is discussed in relation to hormone
      signals involved in renal growth. The importance of the concentration of CTP, and
      thus of CTP synthetase, in the CTP-cytidyltransferase reaction, an enzyme with a
      high Km for CTP, makes the present observation of the striking increase in CTP
      synthetase in STZ diabetes of particular interest in relation to
      phosphatidylcholine formation and hormone signal transduction.

PMID- 1381201
TI  - Functional activity of an HIV-1 neutralizing IgG human monoclonal antibody: ADCC
      and complement-mediated lysis.
AB  - The IgG1 kappa, human monoclonal antibody (HMAb), F105, was studied for
      functional activity in antibody-dependent cellular cytotoxicity (ADCC) and
      complement-dependent cytotoxicity (CDC). F105 reacts with a discontinuous epitope
      on the CD4 binding site of the HIV-1 envelope glycoprotein, gp120, expressed on
      the surfaces of infected cells and neutralizes diverse viral strains at antibody
      concentrations readily achievable in humans. Neither F105 nor serum (diluted
      1:50) from HIV seropositive donors mediate CDC against an SF2-infected cell line
      with rabbit or human sera as a source of complement. F105 and HIV-1 sera mediate
      ADCC against the SF2 strain. Normal human serum reduced spontaneous lysis of SF2
      by peripheral blood monocytes (PBM). Although mixing of F105 with normal human
      serum reduced the lysis observed (36 +/- 8 vs. 42 +/- 8%), this still was
      significantly greater than lysis in media (30 +/- 5%) or normal human serum (23
      +/- 6%) (p less than .05). A murine antibody to CD16 significantly reduced
      spontaneous lysis observed with media (30 +/- 5 vs. 18 +/- 3%) while normal mouse
      serum had no effect (31 +/- 7%). ADCC mediated by F105 is completely abrogated by
      the anti-CD16 antibody (42 +/- 8 vs. 22 +/- 4%), while only a fraction of ADCC
      mediated by HIV sera is inhibited by anti-CD16 (60 +/- 9 vs. 46 +/- 6%),
      suggesting that several populations of effector cells function in ADCC mediated
      by the polyclonal sera. Thus, F105, as opposed to polyclonal sera, mediates ADCC
      through a CD16+ PBM population.

PMID- 1381202
TI  - Class II (I-Ad) restricted T-cell recognition of the V3 loop region of HIV-1
      gp120.
AB  - A CD4+ and gp120-specific T-cell line, and subclone, were established from BALB/c
      mice following immunization with recombinant gp120, using an adjuvant formulation
      (alum) acceptable for use in the human. The recognition specificity was
      determined against a panel of synthetic peptides corresponding to the primary
      sequence of the HXB2 strain of human immunodeficiency virus (HIV). An epitope was
      identified, corresponding to amino acid residues 322-341, and a further series of
      truncated peptides established the minimum determinant to be 327-341. Possible
      reasons for the immunodominance of the V3 loop, and adjacent regions, for both
      antibody and T-cell recognition are discussed.

PMID- 1381203
TI  - Recombinant glycoprotein 120 of human immunodeficiency virus is a potent
      interferon inducer.
AB  - Cells infected with human immunodeficiency virus (HIV) induce antiviral activity
      in peripheral blood mononuclear cells (PBMC) from healthy donors. This activity
      is neutralized by anti-interferon-alpha antibody and partially destroyed at pH 2.
      Previous studies with enriched cell populations and monoclonal antibodies suggest
      that B lymphocytes are the main IFN-producing cells, and that both CD4 and HLA
      class II antigens are essential for IFN induction. Since the initial event of HIV
      infection of CD4+ cells is the interaction of the virus coat glycoprotein gp120
      with CD4 molecule, we investigated whether gp120 is responsible for IFN
      induction. Using PBMC and recombinant gp120 obtained from a baculovirus
      expression system, dose-dependent induction of antiviral activity was observed
      with titers approaching 10(3) IU/ml. This induction was blocked in the presence
      of antibody to gp120. The antiviral activity was characterized as IFN-alpha by
      neutralization with IFN alpha-specific antibody. Preincubation of PBMC with anti
      CD4 or the presence of soluble CD4 during incubation inhibited IFN induction,
      indicating that interaction of gp120 with cell-associated CD4 is responsible for
      this induction. Neither lymphoproliferation nor interleukin-2 (IL-2) production
      was observed during IFN induction. However, class G immunoglobulin secretion was
      enhanced by gp120, indicating that B cells are direct or indirect targets of
      gp120 stimulation in this experimental system. Since gp120 is shed from HIV
      infected cells and occurs in the serum of acquired immunodeficiency syndrome
      (AIDS) patients, our data suggest that this glycoprotein is responsible for the
      induction of endogenous IFN and the polyclonal activation of B cells both of
      which are observed in AIDS patients.

PMID- 1381204
TI  - Pyridoxal-5'-phosphate inhibits the polymerase activity of a recombinant RNAase H
      deficient mutant of HIV-1 reverse transcriptase.
AB  - We have investigated the ability of pyridoxal-5'-phosphate to inhibit a
      recombinant deletion mutant of human immunodeficiency virus type 1(HIV-1) reverse
      transcriptase (RT) which is missing the last 23 amino acids of the C-terminus.
      This mutant reverse transcriptase is characterized by normal polymerase activity
      as compared with full-length enzyme; however, it has no RNase H activity.
      Inhibition studies with pyridoxal-5'-phosphate showed several differences as
      compared with inhibition of full-length enzyme: (1) Inhibition of mutant reverse
      transcriptase was independent of divalent cation, (2) Either substrate alone
      could protect mutant reverse transcriptase from inactivation by pyridoxal-5'
      phosphate, and (3) stoichiometry of pyridoxal-5'-phosphate binding to mutant
      reverse transcriptase was 2 mol/mol under the same conditions in which 1 mol/mol
      bound to full-length enzyme. Furthermore, in the presence of either substrate
      alone, the stoichiometry of pyridoxal-5'-phosphate binding to the mutant was
      reduced to 1 mol/mol. These results indicate that the second binding site for
      pyridoxal-5'-phosphate seen in the mutant reverse transcriptase is at or near the
      primer-template binding site of the enzyme. They also suggest that the RNase H
      domain of HIV RT plays a functional role in substrate binding at the polymerase
      domain.

PMID- 1381205
TI  - Inhibition of the reverse transcriptase activity and replication of human
      immunodeficiency virus type 1 by AS 101 in vitro.
AB  - In a search for compounds active against human immunodeficiency virus type 1 (HIV
      1), it was found that the novel low-molecular weight immunoenhancer ammonium
      trichloro(dioxyethylene-O,O'-) tellurate (AS101) suppresses production of HIV-1
      in vitro. Treatment of HIV-1-infected peripheral blood mononuclear cells (PBMC)
      with increasing concentrations of AS101 resulted in substantial inhibition of
      virus production as measured by both reverse transcriptase (RT) activity and
      antigen presence in supernatants of treated cells. AS101 had no effect on PBMC
      viability, growth, or morphology up to a concentration of 15 microM for 14 days.
      To elucidate a possible mechanism for the inhibition of AS101, we have analyzed
      the effect of the drug on the catalytic functions associated with HIV RT, namely
      the RDDP, DDDP, and RNase H activities. RDDP and DDDP activities were impaired by
      the drug with calculated IC50 value of about 4 microM. On the other hand, the
      RNase H activity was less sensitive to AS101, with an apparent IC50 value of
      about 30 microM. The anti-HIV-1 activity of AS101 as reflected by inhibition of
      the different catalytic functions associated with viral RT, in the absence of
      drug-related toxicity to lymphocytes, together with its immunomodulating activity
      strongly argues in favor of its evaluation, as a therapeutic agent for patients
      with HIV infection.

PMID- 1381206
TI  - Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of
      HIV-1 IIIB replication.
AB  - Down-regulation of Epstein-Barr virus (EBV) induced transformation of human
      lymphocytes in vitro by dehydroepiandrosterone (DHEA), a naturally occurring
      human steroid secreted by the adrenal gland has been demonstrated. This article
      reports on the effects of DHEA and its novel synthetic analogs 16 alpha-fluoro-5
      androsten-17-one (8354) and 3 beta-hydroxy-16 alpha-fluoro-5 alpha-androstan-17
      one (OH8356) on human immunodeficiency virus (HIV-1) replication. Treatment with
      DHEA, 8354, or OH8356 resulted in a modest down-regulation of HIV-1 replication
      in phytohemagglutinin-stimulated peripheral blood lymphocytes as measured by
      syncytia formation, release of p24 antigen, and accumulation of reverse
      transcriptase activity. DHEA and 8354 also reduced syncytia formation in HIV-1
      infected SupT1 lymphoblasts. DHEA and synthetic analogs of DHEA, which have been
      shown previously to have antiproliferative effects, now are shown to reduce HIV-1
      replication. DHEA or synthetic analogs of DHEA could provide an alternative
      and/or adjuvant for HIV-1 infection.

PMID- 1381207
TI  - Studies on a type D retrovirus isolated from an AIDS patient lymphoma.
AB  - The development of AIDS-related lymphomas (ARL) has been on the rise in recent
      years. During an analysis of ARL from AIDS patients, one individual developed
      atypical syncytial variants of high-grade Burkitt's-type B-cell lymphomas, which
      prompted further study. However, the search for a HIV-1 retrovirus, which we
      hypothesized was infecting these cells, led to the subsequent discovery of a type
      D retrovirus in two early-passage lymphoma cell lines derived from this patient.
      Nucleotide and amino acid sequence analysis, as well as immunologic reactivity,
      indicated that the virus was closely related to Mason-Pfizer monkey virus (MPMV)
      or simian retrovirus type 1 (SRV-1). MPMV and SRV-1 are immunosuppressive type D
      retroviruses that cause an AIDS-like syndrome in rhesus macaques. Amplification
      of DNA from the patient's diagnostic bone marrow biopsy specimen by the
      polymerase chain reaction generated MPMV-specific fragments indicative of
      infection by a retrovirus similar to MPMV. Additionally, the patient's serum
      contained antibodies that recognized type D retroviral env proteins (gp20 and
      gp70) and gag proteins (p27 and p14) as assayed by immunoblot and
      radioimmunoprecipitation techniques. Although there have been reports of human
      cell lines infected with type D retroviruses and of type D reactive human sera,
      this is the first report of a type D retrovirus infection in a human confirmed by
      virus isolation, serum immunoreactivity, and viral DNA identification in tumor
      tissue.

PMID- 1381208
TI  - T cell epitopes: synthetic antigens and multiple sclerosis.

PMID- 1381209
TI  - The interferon receptors: an unfinished story.

PMID- 1381212
TI  - Self-replicating systems.

PMID- 1381210
TI  - Clinical and laboratory evaluation of the myeloprotective effect of
      medroxyprogesterone acetate in head and neck cancer.
AB  - The action of high-dose medroxyprogesterone acetate (MPA) was studied by
      analysing the behaviour of colony-forming-unit granulocyte-macrophage (CFU-GM)
      during chemotherapy. 21 non-pretreated men with locally advanced carcinoma of the
      head and neck were randomised into two arms: A (11 patients) received three
      alternating cycles of cisplatin, 5-fluorouracil (CF)/cisplatin, methotrexate,
      bleomycin, vincristine and then CF every 4 weeks and B (10 patients) were treated
      with the same schedule plus 1000 mg per day of MPA. MPA was administered 14 days
      before the start of chemotherapy (day 0) and continued daily up to the 90th day.
      Bone marrow was harvested in arm A on days 0, +14 and +90, and in B, also on day 
      14. There was diverse CFU-GM behaviour in the two arms on the 14th day. These
      data support the hypothesis that the myeloprotective effect of MPA is due to
      induction of a mitotic rest in the stem cells, which protects them from drug
      action.

PMID- 1381211
TI  - Fulminant hepatic failure in non-Hodgkin lymphoma patients treated with
      chemotherapy.
AB  - Chemotherapy is the mainstay of therapy for patients with non-Hodgkin lymphoma.
      Among side-effects associated with the use of chemotherapy, immunosuppression is
      one which can be potentially fatal. In hepatitis B carriers, immunosuppression
      permits widespread infection of the hepatocytes and its subsequent withdrawal
      causes an "immunological rebound" leading to massive necrosis of hepatocytes. 4
      patients who died of fulminant hepatitis following chemotherapy are reported.
      These were patients with positive hepatitis B serology. Caution is advised when
      treating non-Hodgkin lymphoma in patients from hepatitis B endemic regions.

PMID- 1381213
TI  - Immunoreactive "calcitonin-like" material in heroin addicts: varying reactivity
      with different antibodies.
AB  - High levels of immunoreactive calcitonin (iCT) in the blood of heroin addicts
      were previously reported. As it is well known that multiple forms of calcitonin
      exist in the blood and in tissues, the purpose of the present study was to
      investigate the immunological nature of the CT-like immunoreactive material found
      in the blood of these subjects. We investigated 25 addicts, who had been using
      heroin for more than one year and were hospitalized for a 2 week detoxication
      program. Blood samples were drawn at the start of the program (when the subjects
      were still on heroin) and after 5 and 12 days of abstinence from heroin. Twenty
      five healthy subjects served as controls. We used 2 commercial RIA kits,
      calibrated against the same reference material (WHO 70-234), but employing
      different antisera. One antiserum substantially confirmed the previous findings
      of increased levels of calcitonin during heroin use, but the other seemed to
      exclude any change in the hormone concentrations. This suggests that the
      "calcitonin like" material found in heroin addicts contains some epitopes similar
      to those found in the calcitonin standard which are detected by the first
      antiserum. However it lacks other epitopes which are also present in calcitonin
      standard and which are recognized by the second antiserum. Therefore, this
      substance seems to be different from the standard human calcitonin 1-32. A
      possible involvement of a calcitonin analogue (precursor or metabolite) in the
      biochemical changes occurring during chronic opiate use is suggested.

PMID- 1381214
TI  - Rat prostate cancer cell line-specific production and apparent secretion of
      heparin-binding growth factors.
AB  - Cultured C3 and T5 AXC/SSh rat prostate cancer cells and their conditioned media
      contained 1000-fold more heparin-binding mitogens than did normal AXC/SSh rat
      prostates. Immunological analyses confirmed that rat ventral prostate contained
      only a 17.5 kilodalton (kDa) basic fibroblast growth factor (bFGF)-like mitogen.
      In contrast, combined immunological and metabolic radiolabeling analyses showed
      that C3 cells contained 23/24 and 14 kDa bFGF-like polypeptides, whereas the
      principal bFGF-like polypeptides of C3 cell conditioned medium were proteins
      having masses of 17.5 and 14 kDa. Identical analyses showed that T5 cells
      contained 17.5 and 14 kDa bFGF-like polypeptides, whereas the principal bFGF-like
      polypeptides of T5 cell conditioned medium were proteins having masses of 17.5,
      16, and 14 kDa. We found that bFGF-like proteins of mass less than 17.5 kDa,
      which were present in conditioned medium, were not derived by proteolysis of
      higher molecular weight bFGF-like mitogens after these were processed into
      conditioned medium. Northern analyses showed that normal prostate and prostate
      cancer cells contained acidic fibroblast growth factor transcripts of 6.5 and 3.4
      kilobases (kb) and bFGF transcripts of 6.0 and 2.5 kb. Prostate cancer cells also
      contained a 12-kb bFGF transcript that was not present in normal prostate.
      Southern analysis of restriction endonuclease-digested normal prostate or
      prostate cancer cell genomic DNA showed that the 12-kb bFGF transcript was not
      the product of a rearranged bFGF gene. Our data show that rat prostate cancer
      cells contain bFGF-like polypeptides of mass 14 to 23/24 kDa and suggest that
      these cells secrete bFGF-like polypeptides.

PMID- 1381215
TI  - The RNP motif protein family.
AB  - RNA-protein interactions play critical roles in a variety of important processes
      in the cell, such as mRNA splicing and translation. Many RNA binding proteins
      contain an approximately 80-aminoacid conserved sequence, the RNP motif, that has
      been shown in several cases to constitute the binding domain. As a class, RNP
      motif proteins bind many different RNAs with varying degrees of sequence
      specificity. A major area of current interest is the elucidation of the structure
      function relationships in these proteins: the structure of the motif and the
      residues that are important for sequence-specific binding, the roles of the
      individual motifs in proteins with multiple RNP motifs, and the functions of
      other domains found in RNP motif proteins. Recent experiments have provided some
      insight into these issues and have paved the way for a more detailed
      understanding of this protein family.

PMID- 1381216
TI  - FLP-mediated intermolecular recombination in the cytoplasm of Drosophila embryos.
AB  - We show that when a heat-shock-driven gene that encodes the yeast FLP recombinase
      is injected into preblastoderm Drosophila embryos, it promotes intermolecular
      recombination between two coinjected plasmids that bear the specific
      recombination target sequence, FRT. Minimal, 34-bp FRT sites in the two plasmids
      are sufficient for their cointegration. The reaction is efficient enough to
      produce detectable recombinants when one of the plasmids is present in as little
      as 1000 molecules per embryo. This is comparable to the concentration of unique
      chromosomal sites, raising the possibility that integration of injected plasmid
      DNA into FRT-bearing fly chromosomes may also be achievable. Since integrants
      might be stabilized against the reverse excision reaction if the recombinase
      could be provided in a sharp pulse, it is encouraging that efficient plasmid
      cointegration is also achieved when in vitro synthesized FLP RNA rather than DNA
      is injected into the embryos.

PMID- 1381217
TI  - Growth inhibition of human colorectal carcinoma cell lines by tumor necrosis
      factor-alpha correlates with reduced activity of pp60c-src.
AB  - One molecular alteration that has been observed in the majority of colorectal
      carcinomas is the activation of pp60c-src kinase. To address the role of pp60c
      src in growth control of colon carcinoma cell lines, the effects of the biologic
      response modifier, tumor necrosis factor (TNF)-alpha were studied on the
      established HT29 colorectal carcinoma cell line and two clonal variants derived
      from the parental line. In one clone, HT29-A34, approximately 55% growth
      inhibition was observed following a 120-h incubation period with 10(3) U/ml TNF.
      In this TNF-sensitive cell line, pp60c-src immune complex kinase activity was
      reduced 3.9-fold accompanied by only a slight reduction in pp60c-src protein
      levels. Growth inhibition and decreased pp60c-src kinase activity correlated in a
      dose-dependent manner. The HT29-A14 TNF-resistant clone was not growth-inhibited
      by TNF, and no changes in pp60c-src were observed following treatment. Growth
      inhibition also correlated with reduced pp60c-src kinase specific activity in a
      number of other established colon carcinoma cell lines that were TNF-sensitive.
      In TNF-resistant colon carcinoma cell lines, pp60c-src kinase activity and levels
      remained unchanged. When changes in specific activity of pp60c-src were observed
      in sensitive cells, they occurred after decreased [3H]-thymidine uptake was
      observed. Therefore, these changes in pp60c-src activity are not the earliest
      event in TNF-induced growth inhibition. Nevertheless, our results suggest that
      modulation of pp60c-src kinase activity may be important in growth control of
      colorectal carcinoma cell lines.

PMID- 1381218
TI  - Treatment of hairy cell leukemia with granulocyte colony-stimulating factor and
      recombinant consensus interferon or recombinant interferon-alpha-2b.
AB  - Patients with hairy cell leukemia and neutropenia (absolute neutrophil count less
      than 1.5 x 10(9)/L) were treated with recombinant granulocyte colony-stimulating
      factor (G-CSF) at doses of 3.6 and 7.2 micrograms/kg by daily subcutaneous
      injection, until normalization of neutrophil counts occurred. Patients then
      received either recombinant interferon-alpha-2b (r-IFN-alpha-2b) or a unique IFN,
      recombinant consensus IFN (rIFN-con-1), each given at doses of 10 micrograms/m2
      subcutaneously three times a week, coupled with continued daily G-CSF therapy,
      for 3 months. After 3 months the G-CSF was discontinued; patients continued to
      take IFN for 1 year. All 10 patients responded to G-CSF with normalization of
      neutrophil counts within 2 weeks; the increase in neutrophil counts was greater
      in previously splenectomized patients. Four patients were treated with r-IFN
      alpha-2b, and six were treated with rIFN-con-1. No patients developed recurrent
      neutropenia with the initiation of IFN therapy. Nine patients are evaluable for
      response to IFN. Five of six patients demonstrated hematologic improvement with
      rIFN-con-1, with two patients obtaining complete responses. All three patients
      receiving r-IFN-alpha-2b demonstrated hematologic improvement; one complete
      response was observed. Toxicities of both IFNs included influenza-like symptoms.
      We conclude that G-CSF can abrogate the myelosuppressive effects of IFN, and may
      be a useful adjunct to this therapy in neutropenic patients. We conclude that
      rIFN-con-1, the product of a synthetic gene, has activity in the treatment of
      hairy cell leukemia, and merits clinical investigation in other settings.

PMID- 1381219
TI  - Single-flush perfusion with modified Euro-Collins solution: experience in
      clinical lung preservation.

PMID- 1381220
TI  - Human prostatic aldehyde dehydrogenase of healthy controls and diseased
      prostates.
AB  - Aldehyde dehydrogenase (ALDH, EC 1.2.1.3) of the human prostate was the subject
      of investigation in this study. The possible physiological role of aldehyde
      dehydrogenase in the human prostate might be to detoxify aldehydes arising from
      the oxidation of the polyamines via monoamine or diamine oxidases. The specific
      activity of the enzyme with 1 mM propionaldehyde as substrate and 0.5 mM NAD at
      pH 7.4 in the control normal prostates and prostates afflicted with the disease,
      benign prostatic hyperplasia (BPH), was 26.06 +/- 2.96 and 5.17 +/- 0.48 nmol/g
      prostate per min, respectively. When 100 microM gamma-aminobutyraldehyde was used
      as a substrate, the specific activity in the normal controls and prostates with
      benign prostatic hyperplasia was 19.80 +/- 1.33 and 2.95 +/- 2.46 nmol/g prostate
      per min, respectively. Upon isoelectric focusing of the extracts of the control
      prostates when the gels were developed for aldehyde dehydrogenase activity, there
      were three aldehyde dehydrogenase activity bands visible, pI 4.9 (mitochondrial),
      5.4 (cytosolic) and about 6.0-6.5, on the IEF gels developed with gamma
      aminobutyraldehyde as a substrate. With the extracts of prostates with benign
      prostatic hyperplasia the pI 4.9 band was significantly reduced, the pI 5.4 band
      enhanced and the approx. pI 6.0 band was not detectable on the IEF gels with
      propionaldehyde as a substrate. There was no detectable aldehyde dehydrogenase
      activity in the extract of the prostate with cancer on IEF gels nor in the
      activity assays with propionaldehyde or gamma-aminobutyraldehyde as substrates.

PMID- 1381222
TI  - Isolation, mass spectrometric characterization, and protein phosphatase
      inhibition properties of cyclic peptide analogues of gramicidin-S from Bacillus
      brevis (Nagano strain).
AB  - Six substitutional variants of gramicidin-S, present in a commercial extract of
      Bacillus brevis, have been characterized using a combination of liquid
      chromatographic/mass spectrometric analysis of the crude extract, plus accurate
      mass measurements, tandem mass spectrometric investigations, and amino acid
      analyses, of isolated high-performance liquid chromatographic fractions. Two of
      these variants were shown previously (Nozaki and Muramatsu, J. Antibiotics 37,
      689 (1984)) to involve replacement of one or both Val residues in gramicidin-S by
      aminobutyric acid, and these findings are confirmed here. One of the four unknown
      variants corresponds to substitution of one Val residue by Leu, while the other
      three all involve substitution of one of the Orn residues in gramicidin-S by Lys,
      or by citrulline (gamma-carbamoyl ornithine), or by gamma-formyl ornithine. The
      biological activities of the purified fractions were assessed with respect to
      their in vitro inhibition of protein phosphatases PP1 and PP2A. For both protein
      phosphatases inhibition levels fell in the micromolar range, about four orders of
      magnitude higher than IC50 values for other small cyclic peptides such as
      microcystins and nodularins.

PMID- 1381221
TI  - Ionic selectivity of volume-sensitive currents in human epithelial cells.
AB  - The ion selectivity of swelling-activated Cl- currents has been investigated in
      three different human epithelial cell lines, two derived from the airway
      epithelium (9HTEo- and CFNPE9o-) and one from a colon carcinoma (T84). The
      relative permeability of volume-sensitive currents with respect to Cl- is: I-
      (1.19) greater than NO3- (1.07) approximately Br-(1.05) greater than Cl-(1.0)
      greater than F-(0.5) approximately HCO3-(0.48) greater than isethionate(0.28)
      greater than aspartate (0.14) approximately gluconate(0.13) approximately SO4(2
      )(0.12). This type of ion selectivity is similar to that described for
      depolarization-activated outwardly rectifying Cl- channels found in epithelial
      cells.

PMID- 1381223
TI  - Preparation and properties of the immunoconjugate composed of anti-human colon
      cancer monoclonal antibody and mitomycin C-dextran conjugate.
AB  - Monoclonal antibody (mAb) A7, produced against human colon cancer, was conjugated
      with a polymeric prodrug of mitomycin C (MMC), the MMC-dextran conjugate with an
      anionic charge (MMCDan) and a molecular weight of 70,000. The amino groups were
      introduced into the MMCDan by reacting ethylenediamine with the carboxyl group in
      the spacer arm of the dextran bridge by a carbodiimide-catalyzed reaction. The
      coupling to mAb A7 was performed using SPDP. A 15 M excess of ethylenediamine
      produced an optimal MMCDan with amino groups, which resulted in a homogenous
      conjugate (A7-MMCD) with minimal formation of high-molecular-weight aggregates in
      about a 30% yield of both IgG and MMC. The molar binding ratio of IgG:dextran:MMC
      in A7-MMCD was estimated to be 1:1.2:40. A7-MMCD, having MMC prodrug properties,
      released active MMC with a half-life of 29.1 h and had an almost neutral electric
      charge under physiological conditions. A competitive binding assay using 125I
      labeled A7 revealed that the A7-MMCD almost fully retained its antibody-binding
      activity. The cytotoxicity of A7-MMCD was assayed by determining the degree of
      inhibition of [3H]-thymidine in corporation in two different ways using the human
      colon cancer cell line SW1116. A 48-h continuous exposure test revealed that the
      pharmacological activity of MMC in A7-MMCD was completely preserved. In addition,
      A7-MMCD exhibited about a 14-fold greater cytotoxicity than MMCDan when the IC50
      values determined using a 2-h pretreatment exposure system were compared. These
      results suggest that A7-MMCD could be useful in immunotargeting chemotherapy for
      colorectal cancer.

PMID- 1381224
TI  - Molecular amplifiers: synthesis and functionalization of a
      poly(aminopropyl)dextran bearing a uniquely reactive terminus for univalent
      attachment to biomolecules.
AB  - The synthesis and characterization of the versatile dextran-based molecular
      amplifier 6 is described. Dextran (Mr = 40,200) was selectively
      monofunctionalized in high yield at its reducing terminus via reductive amination
      with 2-(4-nitrophenyl)ethylamine to give 1. The nitro group in 1 serves as a
      masked amino group which is eventually converted into a reactive isothiocyanato
      group used for monovalent attachment of the completed assembly to a target
      molecule. Cyanoethylation of 1 gave the terminally nitrophenylated
      poly(cyanoethyl)dextran 5 which was selectively reduced to the corresponding
      poly(aminopropyl) derivative 6 with BH3.THF, a reagent which preserved the end
      nitro group. Conjugation of amplifier 6 with the isothiocyanate-derivatized
      Gd(III) chelate 7 gave conjugate 9 containing about 22 mol of chelate/mol of
      amplifier. The T1 relaxivity per Gd(III) ion of 9 in H2O was 15.0 mM-1 s-1, about
      3-fold higher than that of free Gd(III)DTPA in H2O. The nitro group of 9 was then
      selectively reduced to the corresponding amine 10, which was converted into
      isothiocyanate 11. The reactivity of the single isothiocyanate group in 11 was
      demonstrated by coupling to 5-aminoeosin, giving conjugate 12. Amplifier 6 was
      also conjugated with the acid-labile N-cis-aconityl derivative 8 of the potent
      anticancer agent daunomycin. The nitro group of the resulting conjugate 13 was
      then reduced and the resulting amine 14 was converted into mono isothiocyanate
      15. Compound 15 reacted with a water-insoluble amine-containing solid support to
      give 16. Free daunomycin was released from 16 by exposure to citrate-phosphate
      buffer at pH 4.0.

PMID- 1381225
TI  - Evaluation of commercially available antibodies to cytokeratin intermediate
      filaments and laminin in normal cat pinna.
AB  - The pattern of distribution of cytokeratin (CK) intermediate filaments can be
      used to characterize subsets of epithelial tissues. The purpose of the study was
      to examine the CK expression of feline pinna skin. Six normal feline pinnae were
      routinely processed in formalin. An immunohistochemical method was used to stain
      the pinnae with 8 commercially available anti-human CK antibodies (Abs) (PKK1,
      CAM 5.2, UCD 10/11, 35BH11, 34BE12, AE1/AE3, MAK 6, A575) and an anti-human
      laminin Ab. All the CK Abs selectively localized to epithelium except 35BH11,
      which did not react with any part of the pinna. Some epithelial subsets were
      identified by their unique staining pattern with CK Abs. Basal cells but not
      suprabasal cells of the epidermis stained with PKK1; basal but not lumenal cells
      of apocrine glands stained with 34BE12. Apocrine glands stained with all CK Abs
      except 35BH11. All epithelial structures were stained with A575. Basal lamina of
      epithelial and mesenchymal tissues was clearly identified by the anti-laminin Ab.
      The results indicate that in cat pinna some commercially available anti-human CK
      Abs selectively stain subsets of epithelium and adnexa. PKK1, 34BE12, and A575
      were the CK Abs with the most consistent staining patterns, the other Abs stained
      more variably from pinna to pinna. The pattern of epithelial and adnexal staining
      was similar but not identical to that reported for humans.

PMID- 1381226
TI  - Fixation of aldehydic dextrans onto human deoxyhemoglobin.
AB  - A procedure commonly used to transform native adult human hemoglobin (Hb) into a
      physiological oxygen carrier consists of a pyridoxylation of the protein to lower
      its oxygen affinity, followed by its polymerization in the presence of
      glutaraldehyde, with or without further reduction, to increase its circulating
      half-life. This series of reactions yields derivatives presenting a great
      molecular heterogeneity that have to be fractionated for use in vivo. Hemoglobin
      derivatives with low oxygen affinity and a narrow distribution of molecular
      weights were obtained by linking a dextran polyaldehydic derivative to
      deoxyhemoglobin at pH 8. From oxygen-binding measurements carried out in the
      presence of inositolhexaphosphate, a strong effector of hemoglobin, it appeared
      that the allosteric site of hemoglobin was blocked, probably by crosslinking
      bonds, which stabilizes its deoxy structure. On the other hand, when the reaction
      was performed in the presence of inositolhexaphosphate, the resulting conjugates
      exhibited an oxygen affinity identical to that of unmodified hemoglobin. After
      treatment with NaBH4, the polymer-hemoglobin derivatives were stable and
      possessed a reversible oxygen-carrying capacity similar to that of blood. The
      conjugates prepared from oxyhemoglobin all possessed a lower P50 than native
      hemoglobin whatever the reaction conditions.

PMID- 1381227
TI  - Tumour necrosis factor induction of ELAM-1 and ICAM-1 on human umbilical vein
      endothelial cells--analysis of tumour necrosis factor-receptor interactions.
AB  - Induction of the adhesion molecules ELAM-1 and ICAM-1 on endothelial cells is a
      key pro-inflammatory effect of tumour necrosis factor (TNF). Earlier work in non
      human systems has suggested that unlike other cell types, endothelial cells
      interact with the N-terminus of the TNF molecule, thereby implying novel TNF
      receptors on endothelial cells. This is also supported by 125I-TNF cross-linking
      studies on bovine endothelial cells. The present study aimed to see whether TNF
      induction of ELAM-1 and ICAM-1 on human umbilical vein endothelial cells (HUVECs)
      involved novel TNF-receptor interactions. Three approaches were employed. First,
      antibodies directed at different sites on the TNF molecule were tested for
      inhibition of TNF-induction of ELAM-1 and ICAM-1 on HUVECs. Inhibition was seen
      only with antibodies reacting with epitopes outside the N-terminal region.
      Second, an N-terminal TNF peptide (residues 1-26) failed to induce ELAM-1 and
      ICAM-1 on HUVECs or antagonise TNF induction of these molecules. Third,
      HUVEC/125I-TNF cross-linking revealed a major complex characteristic of the known
      55 kDa TNF receptor: this was confirmed with receptor-specific monoclonal
      antibodies. It is concluded that (a) the same part of the TNF molecule interacts
      with TNF-receptors on HUVECs and other cell types and (b) TNF induction of ELAM-1
      and ICAM-1 on HUVECs is mediated via the well-characterized 55 kDa TNF receptor.

PMID- 1381228
TI  - Alpha-fetoprotein expression in hepatocellular carcinoma: a clinical study.
AB  - Alpha-fetoprotein (AFP) levels were studied in 51 consecutive patients with
      hepatocellular carcinoma that presented to the Surgical Hepatobiliary Unit at
      Westmead Hospital over 12 years. Twenty-three were hepatitis surface antigen
      (HBsAg) positive and 13 of those patients were Asian. Thirteen patients drank
      more than 60 g of alcohol each day. A significantly raised level of AFP was
      defined as more than 20 ng/mL, and 31 of the 51 patients had AFP levels exceeding
      this at some stage during surveillance. Twenty-five demonstrated levels above 200
      ng/mL. Univariate statistical methods suggested that men were more likely to
      express raised AFP than women, Asians more likely than other races, patients with
      chronic active hepatitis more likely than those without and those with chronic
      hepatitis B infection more likely than those who were HBsAg negative. Those who
      drank more than 60 g alcohol each day were less likely to demonstrate a raised
      serum AFP than those who drank less. Multivariate logistic regression
      demonstrated that HBsAg carriage was the only statistically significant
      independent determinant of a raised AFP. Age 65 years or more was associated with
      a chance of a raised AFP.

PMID- 1381229
TI  - Beta/A4 deposits and their relationship to senile plaques in Alzheimer's disease.
AB  - The density and spatial pattern of immunostained beta/A4 deposits and mature
      senile plaques (SP) stained by the Glees method were compared in Alzheimer's
      diseased brain. Thirty-seven percent of the variance in Glees SP density in a
      tissue could be explained by beta/A4. Both lesions were clustered with the
      beta/A4 clusters often larger than the Glees SP clusters. Beta/A4 and Glees SP
      cluster size were not correlated in a tissue. The size of Glees SP clusters was
      positively correlated with SP density but no correlation could be detected for
      beta/A4. Hence, the density and spatial pattern of beta/A4 deposits in most
      tissues did not predict the development of Glees SP.

PMID- 1381230
TI  - Galanin- and CGRP-like immunoreactivity coexist in rat spinal motoneurons.
AB  - We can report, that by the use of indirect immunofluorescence techniques, that
      rat spinal motoneurons contain galanin-like immunoreactivity (LI). Furthermore,
      that galanin and calcitonin gene-related peptide (CGRP)-LI coexist in a number of
      spinal motoneurons. Co-localization could be demonstrated as thoracic, lumbar as
      well as sacral spinal cord levels in individual neurons by studying adjacent
      sections each stained by one of the two antisera, as well as by double labelling
      experiments. Small neurons, within the gamma-motoneuron and interneuron size
      range, were also positive for galanin-LI.

PMID- 1381231
TI  - Colocalization of nitric oxide synthase and NADPH-diaphorase in cultured
      myenteric neurones.
AB  - Nitric oxide synthase immunoreactivity and NADPH-diaphorase activity were
      examined in explant culture preparations of the myenteric plexus from beneath the
      taenia coli of the guinea-pig caecum. Nitric oxide synthase immunoreactive
      neurones formed approximately one third of the total neuronal population. NADPH
      diaphorase positive neurones, demonstrated histochemically, constituted a similar
      proportion of the total number of neurones. Immunocytochemistry and NADPH
      diaphorase histochemistry performed on the same preparations revealed that all
      nitric oxide synthase immunoreactive neurones expressed NADPH-diaphorase
      activity. This histochemical evidence is consistent with the view that nitric
      oxide may act as a regulatory agent in the guinea-pig caecum.

PMID- 1381232
TI  - Structure of the mouse 5-HT1C, 5-HT2 and stomach fundus serotonin receptor genes.
AB  - By analysis of the mouse 5-HT1C receptor gene we found that its coding region
      contains three introns. We next isolated cDNA and genomic clones for the closely
      related 5-HT2 receptor using a probe derived from the 5-HT1C receptor sequence.
      This probe also hybridized to an additional gene, called SRL (Serotonin Receptor
      Like). We have evidence demonstrating that it encodes the stomach fundus 5-HT
      receptor. Two introns are present within the coding regions of the mouse 5-HT2
      receptor gene and the SRL gene at positions which correspond to those of introns
      in the 5-HT1C receptor gene. This intron distribution is unique and distinguishes
      these receptors from other members of the family of receptors coupled to G
      proteins.

PMID- 1381233
TI  - Isolation and characterization of two wound-regulated tomato extensin genes.
AB  - Extensins comprise a family of structural cell wall hydroxyproline-rich
      glycoproteins in plants. Two tomato genomic clones, Tom J-10 and Tom L-4, were
      isolated from a tomato genomic DNA library by in situ plaque hybridization with
      extensin DNA probes. Tom J-10 encoded an extensin with 388 amino acid residues
      and a predicted molecular mass of 43 kDa. The Tom J-10 encoded extensin lacked a
      typical signal peptide sequence, but contained two distinct protein domains
      consisting of 19 tandem repeats of Ser-Pro4-Ser-Pro-Lys-Tyr-Val-Tyr-Lys at the
      amino terminus which were directly followed by 8 tandem repeats of the consensus
      sequence Ser-Pro4-Tyr3-Lys-Ser-Pro4-Ser-Pro at the carboxy terminus. RNA blot
      hybridization analysis with the Tom J-10 extensin probe demonstrated the presence
      of a 4.0 kb tomato stem mRNA which accumulated markedly in response to wounding.
      Tom L-4 encoded an extensin with 322 amino acid residues and a predicted
      molecular mass of 35 kDa. The Tom L-4 encoded extensin contained a typical signal
      peptide sequence at the amino terminus and was followed by at least 3 distinct
      domains. These domains consisted of an amino terminal domain containing several
      Lys-Pro and Ser-Pro4 repeat units, a central domain with repeats of the consensus
      sequence Ser-Pro2-5-Thr-Pro-Ser-Tyr-Glu-His-Pro-Lys-Thr-Pro, and a carboxy
      terminal domain containing repeats of the consensus sequence Ser-Ser-Pro4-Ser-Pro
      Ser-Pro4-Thr-Tyr1-3. RNA blot hybridization analysis with the Tom L-4 extensin
      probe demonstrated the presence of a 2.6 kb tomato stem mRNA which accumulated in
      response to wounding.

PMID- 1381234
TI  - Membrane glycoprotein CD36: a review of its roles in adherence, signal
      transduction, and transfusion medicine.

PMID- 1381235
TI  - Defective transport as a mechanism of acquired resistance to methotrexate in
      patients with acute lymphocytic leukemia.
AB  - Although the mechanisms of resistance to methotrexate (MTX) are known in
      experimental tumors made resistant to this drug, little information is available
      regarding acquired resistance to MTX in patients. A competitive displacement
      assay using the fluorescent lysine analogue of MTX, N-(4-amino-4-deoxy-N10
      methylpteroyl)-N epsilon-(4'-fluorescein-thiocarbamyl)-L-lysine (PT430), was
      developed as a sensitive method of detection of transport resistance to MTX in
      cell lines, as well as in blast cells from patients with leukemia. Rapid uptake
      of PT430 at high concentrations (20 mumol/L) in leukemic blasts resulted in
      achievement of steady-state levels within 2 hours. Subsequent incubation with the
      folate antagonists, MTX and trimetrexate (TMTX), which differ in the mode of
      carrier transport, produced characteristic patterns of PT430 displacement. Flow
      cytometric analysis of the mean fluorescence intensity in the human CCRF-CEM T
      cell lymphoblastic leukemia cell line and its MTX-resistant subline clearly
      identified the presence of transport deficiency in the resistant subline.
      Analysis of blasts from 17 patients with leukemia, nine with no prior
      chemotherapy and eight previously treated with chemotherapy, found evidence of
      MTX transport resistance in two of the four patients who were treated with MTX
      and considered to be clinically resistant to the drug. The finding that blast
      cells of some patients with leukemia considered clinically resistant to MTX is
      due to decreased MTX transport has important implications for clinical use of
      this drug and for new drug development.

PMID- 1381236
TI  - Diethyldithiocarbamate induction of cytokine release in human long-term bone
      marrow cultures.
AB  - Diethyldithiocarbamate (DDTC) is a biochemical modulating agent that protects
      murine bone marrow progenitor cells from the cytotoxicity of a variety of cancer
      chemotherapeutic agents. However, the mechanism of this protection is not well
      understood. Long-term human bone marrow cultures (LTBMC) were established and at
      day 17 treated with 30 mumol/L DDTC for 1 hour, after which DDTC was removed and
      replaced with complete medium. Conditioned medium was then collected 6, 12, 24,
      and 48 hours later and analyzed for the presence of cytokines. A time-dependent
      increase in granulocyte-macrophage colony-stimulating factor (GM-CSF) (12-fold),
      granulocyte-CSF (G-CSF) (66-fold), interleukin (IL)-6, (three-fold), IL-1 beta
      (161-fold), and tumor necrosis factor (TNF)-alpha (25-fold) was observed. The
      maximum increase for the factors other than TNF-alpha was at 24 to 48 hours
      posttreatment. However, TNF-alpha peaked as early as 6 hours post-DDTC. When
      conditioned medium from these cultures was tested in a granulocyte-macrophage
      progenitor cell (GM-CFC) assay, an increase in colony formation was observed that
      correlated with the increased levels of cytokines in the medium. The specificity
      of this effect was confirmed by the fact that the closely related congener
      bis(hydroxyethyl)dithiocarbamate was devoid of colony-stimulating activity. The
      addition of antibodies for TNF-alpha and/or IL-1 alpha following DDTC treatment
      did not inhibit the release of GM-CSF, G-CSF, or IL-6 from the LTBMC. These
      results suggest that DDTC accelerates bone marrow recovery following myelotoxic
      drug treatment via increased production of cytokines that are known to be
      essential for hematopoiesis.

PMID- 1381237
TI  - Bone marrow stromal fibroblasts secrete interleukin-6 and granulocyte-macrophage
      colony-stimulating factor in the absence of inflammatory stimulation:
      demonstration by serum-free bioassay, enzyme-linked immunosorbent assay, and
      reverse transcriptase polymerase chain reaction.
AB  - Bone marrow (BM) stromal fibroblasts produce hematopoietic growth factors (HGFs)
      in response to inflammatory mediators such as tumor necrosis factor-alpha or
      interleukin-1 alpha (IL-1 alpha). In the absence of such inflammatory stimuli,
      production of HGFs by BM stromal cells has been problematic and controversial. In
      vivo, however, basal hematopoiesis maintains blood counts within a normal
      homeostatic range even in the absence of inflammation, and HGFs are required for
      progenitor cell differentiation in vitro. To better ascertain the contribution of
      BM stromal fibroblasts to basal hematopoiesis, we therefore studied HGF
      production in quiescent BM stromal fibroblasts by three sensitive assays: serum
      free bioassay, enzyme-linked immunosorbent assay, and reverse transcriptase
      polymerase chain reaction. Stromal fibroblasts were cultured in the presence or
      absence of normal human serum to determine if serum factor(s) present in the
      noninflammatory (basal) state induce secretion of HGFs. Human serum was found to
      induce or enhance transcription and secretion of granulocyte-macrophage colony
      stimulating factor (GM-CSF) and enhance secretion of constitutively expressed IL
      6. In contrast, no secretion of either granulocyte-CSF (G-CSF) or IL-3 was found.
      These data indicate that factors in normal human serum are active in enhancing GM
      CSF and IL-6 production by stromal fibroblasts and suggest that these growth
      factors contribute to the maintainance of normal, basal hematopoiesis in vivo.

PMID- 1381238
TI  - Effects of human stem cell factor (c-kit ligand) on proliferation of myeloid
      leukemia cells: heterogeneity in response and synergy with other hematopoietic
      growth factors.
AB  - A novel hematopoietic growth factor, the stem cell factor (SCF), for primitive
      hematopoietic progenitor cells has recently been purified and its gene has been
      cloned. In this study we tested the mitogenic activity of recombinant human SCF
      on myeloid leukemia cells as well as the expression of its receptor. We have
      investigated the proliferation of 31 myeloid leukemia cell lines as well as fresh
      myeloid leukemic blasts from 17 patients in a 72-hour 3H-thymidine uptake assay
      in the presence of various concentrations of recombinant human (rh) SCF alone or
      in combination with saturating concentrations of granulocyte-macrophage colony
      stimulating factor (GM-CSF), G-CSF, M-CSF, interleukin-3 (IL-3), or
      erythropoietin (EPO). Only five of 31 lines, but fresh leukemic blasts from 12 of
      17 patients with acute myeloid leukemia (AML), significantly responded to SCF.
      The responding cell lines were of the acute promyelocytic, chronic myeloid,
      megakaryoblastic, and erythroleukemia origin, the responding blast preparations
      of all French-American-British subtypes. Synergistic activities of SCF were found
      with G-CSF, GM-CSF, EPO, and IL-3. To determine the SCF binding sites on leukemic
      cells, we used 125I-radiolabeled SCF in Scatchard analysis and cross-linking
      studies. The leukemic cell lines responding to SCF expressed from 2,300 up to
      29,000 binding sites per cell. The SCF receptor expression was downregulated in
      vitro by the presence of its ligand. Cross-linking studies demonstrated a 150-Kd
      SCF receptor on the surface of all responding myeloid leukemias. This study
      suggests that SCF may be an important factor for the growth of myeloid leukemia
      cells, either as a direct stimulus or as a synergistic factor for other
      cytokines. Furthermore, using polymerase chain reaction analysis of total RNA
      from the myeloid leukemia lines, we found expression of SCF-mRNA in 17 of 30
      lines, suggesting autocrine mechanisms in the growth of a subgroup of leukemic
      cells by coexpression of SCF and its receptor.

PMID- 1381239
TI  - Kit ligand improves in vitro erythropoiesis in myelodysplastic syndrome.
AB  - Erythropoiesis in response to erythropoietin (Epo) in myelodysplastic syndrome
      (MDS) in vitro and in vivo is severely impaired. We investigated the stimulative
      effect of c-kit ligand (KL) on the erythroid colony-forming abilities of bone
      marrow cells from 17 patients with MDS. The effects of normal donor-derived
      marrow were examined in comparison. Suppression of erythroid colony formation in
      MDS in response to Epo could not be restored by the addition of interleukin-3 (IL
      3) to culture. In cultures dishes supplemented with KL, erythroid colony
      formation was dramatically enhanced, regarding both colony number and size.
      Colony-forming abilities by MDS progenitors were improved following costimulation
      with KL, particularly in refractory anemia (RA) and refractory anemia with ring
      sideroblasts (RARS); however, little enhancement was apparent following KL
      stimulation of marrow from patients with refractory anemia with excess of blasts
      (RAEB), refractory anemia with excess of blasts in transformation (RAEB-t), and
      chronic myelomonocytic leukemia (CMML). These results suggest that KL
      responsiveness of patients with low-risk MDS may still be intact, and that with
      progression to high-risk MDS, erythroid progenitors lose proliferative reactivity
      to both KL and Epo stimulation. KL may have a therapeutic role in restoring
      erythropoiesis in a subset of patients with MDS.

PMID- 1381240
TI  - Interleukin-11 stimulates multiple phases of erythropoiesis in vitro.
AB  - Interleukin-11 (IL-11), a pleiotropic cytokine originally isolated from a primate
      bone marrow stromal cell line, has been shown to stimulate T-cell-dependent B
      cell maturation, megakaryopoiesis, and various stages of myeloid differentiation,
      but to inhibit adipogenesis. Because stromal cells are essential for the
      maintenance of early hematopoietic progenitor cells in long-term culture, we
      investigated the effects of IL-11 on multipotent and erythroid precursors from
      murine bone marrow in vitro in suspension and semisolid cultures. Our results
      show that in the presence of IL-3 or c-kit ligand (KL), IL-11 has profound
      stimulatory effects on primitive multilineage hematopoietic progenitors, pre
      CFC(multi), as well as on precursors representing various stages of erythroid
      differentiation observable in vitro, including CFC(multi), BFU-E, and CFU-E. In
      addition, the combination of KL with IL-11 also stimulated highly proliferative
      erythroid progenitors that yield remarkable macroscopic erythroblast colonies in
      culture. These results indicate that IL-11 is likely to play a pivotal role in
      early hematopoiesis and at multiple stages of erythropoiesis.

PMID- 1381241
TI  - Functional expression of c-kit by acute myelogenous leukemia blasts is enhanced
      by tumor necrosis factor-alpha through posttranscriptional mRNA stabilization by
      a labile protein.
AB  - The c-kit proto-oncogene encodes a transmembrane glycoprotein identical to the
      receptor for the recently cloned stem cell factor (SCF). The present study
      examines constitutive synthesis of transcripts in primary acute myelogenous
      leukemia (AML) blasts and the effects of recombinant human tumor necrosis factor
      (TNF)-alpha on c-kit mRNA expression in these cells. The c-kit transcripts were
      detectable at low levels in 10 of 10 different AML samples investigated. TNF
      treatment of AML cells was associated with enhanced c-kit mRNA expression in all
      specimens. Nuclear run-on transcription assays indicated that the c-kit gene was
      transcriptionally active in all leukemias examined and the rate of transcription
      was unaffected by exposure to TNF, suggesting posttranscriptional control
      mechanisms of c-kit mRNA accumulation. In the absence of TNF, the half-life of c
      kit transcripts was 2 to 3 hours, while in TNF-treated AML cells, c-kit half-life
      was found to be 5 to 9 hours. Inhibition of protein synthesis reduced TNF-induced
      c-kit mRNA expression by Northern blot analysis, but did not affect the rate of c
      kit gene transcription. In the presence of inhibition of protein synthesis, the
      half-life of c-kit transcripts in TNF-induced leukemia cells decreased to 2 to 4
      hours. These findings indicate that levels of c-kit mRNA are controlled by a
      labile protein that is involved in TNF-mediated stabilization of c-kit
      transcripts. The effects of TNF-alpha also extended to the protein level in that
      TNF-alpha treatment of primary AMLs was associated with enhanced surface
      expression of the SCF receptor by some of these cells. While exogenous SCF
      induced clonogenic growth of all primary AML samples investigated, TNF-alpha
      failed to stimulate leukemic cells to proliferate. However, the combination of
      SCF and TNF-alpha resulted in synergistic growth stimulation in seven of nine
      different AML specimens investigated. The finding of transmodulation of the SCF
      receptor through posttranscriptional modifications might further contribute to
      our understanding of the synergistic interplay of TNF-alpha and SCF.

PMID- 1381242
TI  - Human fetal liver-derived CD7+CD2lowCD3-CD56- clones that express CD3 gamma,
      delta, and epsilon and proliferate in response to interleukin-2 (IL-2), IL-3, IL
      4, or IL-7: implications for the relationship between T and natural killer cells.
AB  - Cells from fetal liver or fetal and adult bone marrow that are membrane (m)CD3
      negative and have not rearranged TCR genes but express CD3 proteins in their
      cytoplasm are considered to be committed T-cell progenitors. Recent findings
      question whether CD3 is T-cell specific because fetal natural killer (NK) cells
      have been shown to express cCD3 delta and epsilon proteins. To further examine
      the relationship between T and NK cells, we generated mCD3-cCD3+ clones from
      fetal liver. Two stable clones, FL412 and FL508, isolated from different donors,
      were selected on the basis of absence of the NK cell marker CD56. These clones
      shared a common phenotype of CD7+CD2lowCD3-CD4-CD8-CD5-CD6-CD11b+CD16-CD56 -.
      Like fetal NK clones, these clones expressed cytoplasmic CD3 delta and epsilon
      transcripts and proteins. However, the clones exhibited no or very low levels of
      cytotoxic activity against K562, JY, or Daudi, which were lysed efficiently by
      fetal NK clones. TCR beta, gamma, and delta genes in these clones were in
      germline configuration. Furthermore, both FL412 and FL508 responded not only to
      interleukin-2 (IL-2), IL-4, or IL-7, but also to IL-3 with proliferation. These
      results suggest that FL412 and FL508 retained some characteristics of a putative
      T or NK precursor in the fetal liver and may be useful for analyses of this
      poorly defined cell type.

PMID- 1381243
TI  - Interleukin-4 inhibits both paracrine and autocrine tumor necrosis factor-alpha
      induced proliferation of B chronic lymphocytic leukemia cells.
AB  - The proliferative response of purified malignant B cells from 26 patients with
      chronic lymphocytic leukemia (CLL) was investigated in vitro. In the majority of
      these patients, a proliferative response could be induced by the combination of
      tumor necrosis factor (TNF)-alpha and PMA. The concentration of PMA was found to
      be critical and showed a sharp optimum. In most cases maximal proliferation was
      obtained with as little as 0.1 ng/mL PMA. In all cases tested, TNF-alpha-induced
      proliferation could be inhibited completely by the addition of low doses of
      interleukin-4 (IL-4). Maximal inhibition was already found with 400 pg/mL IL-4.
      Inhibition by IL-4 was not caused by a downmodulation of TNF receptors. Apart
      from TNF-alpha, IL-2 was also in synergy with PMA able to induce proliferation in
      B-CLL cells of some patients. This IL-2-induced proliferation could be inhibited
      both by IL-4 and by neutralizing anti-TNF-alpha antibodies. This shows that TNF
      alpha also can act as an autocrine growth factor. These data indicate that TNF
      alpha is an important growth factor for neoplastic B-CLL cells and that IL-4
      provides a tool to interfere with this TNF-alpha response.

PMID- 1381244
TI  - Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from
      children with hyperdiploid (greater than 50 chromosomes) B-lineage acute
      lymphoblastic leukemia: a Pediatric Oncology Group study.
AB  - Hyperdiploidy (greater than 50 chromosomes, or a DNA index greater than 1.16)
      confers a favorable prognosis in B-lineage acute lymphoblastic leukemia of
      childhood. Children with B-lineage acute lymphoblastic leukemia whose
      lymphoblasts at diagnosis accumulate high levels of methotrexate (MTX) and MTX
      polyglutamates (MTXPGs) in vitro experience a better event-free survival than
      those whose lymphoblasts do not (Blood 76:44, 1990). Lymphoblasts from 13
      children with hyperdiploidy (greater than 50 chromosomes) accumulated high levels
      of MTX-PGs (1,095 and 571 to 2,346 pmol/10(9) cells [median and 25% to 75%
      intraquartile range]). These levels were higher than those in B-lineage
      lymphoblasts from 19 children with other aneuploidy (326 and 159 to 775
      pmol/10(9) cells) and 15 children with diploidy (393 and 204 to 571 pmol/10(9)
      cells) (P = .0015). Chromosomal trisomies in hyperdiploid cases were highly
      nonrandom. Chromosome 9 was not one of the chromosomes involved in trisomies,
      even though this chromosome contains the gene for folate polyglutamate
      synthetase, which is the enzyme required for MTXPG synthesis. The correlation
      between MTXPG level and percentage of S-phase cells was weak, suggesting that
      increased levels of MTXPGs could not be attributed to elevated proportions of
      cells in active DNA synthesis. The ability of hyperdiploid lymphoblasts to
      accumulate high levels of MTXPGs may increase their sensitivity to MTX
      cytotoxicity, accounting in part for the improved outlook for hyperdiploid
      patients treated with regimens that emphasize MTX as a primary component of
      continuation therapy.

PMID- 1381245
TI  - FK 506: a new immunosuppressive agent for organ transplantation. Pharmacology,
      mechanism of action and clinical applications.

PMID- 1381246
TI  - Inflammatory mediators and the pathogenesis of inflammatory bowel disease.

PMID- 1381248
TI  - Recombinant human granulocyte-colony-stimulating factor in the treatment of
      patients with chronic benign granulocytopenia and congenital agranulocytosis
      (Kostmann's syndrome).
AB  - Seven patients with chronic benign granulocytopenia and nine patients with
      congenital agranulocytosis, received consecutive seven-day courses of recombinant
      human granulocyte-colony stimulating factor at a starting dose of 50
      micrograms/m2/day, subcutaneously. If there was no response the doses were
      increased to 300 micrograms/m2. All patients with chronic benign granulocytopenia
      responded rapidly at the minimum dose within 1-3 days after administration. By
      contrast, only three of the nine patients with congenital agranulocytosis
      responded within 1-7 days at this dose. Four patients with congenital
      agranulocytosis showed a response between days 7-19 at a dose of granulocyte
      colony-stimulating factor 100-200 micrograms/m2 but in the remaining two cases no
      response was obtained. The administration of granulocyte-colony-stimulating
      factor was shown to be safe and effective also in reducing infectious episodes in
      these patients. Previously it was reported that granulocyte-colony-stimulating
      factor 10-30 micrograms/kg/day was effective for patients with congenital
      agranulocytosis. These results indicate that patients with congenital
      agranulocytosis may require much higher doses of recombinant human granulocyte
      colony-stimulating factor than patients with chronic benign granulocytopenia and
      that the response to ordinary doses of recombinant human granulocyte-colony
      stimulating factor may be useful in differentiating between chronic benign
      granulocytopenia and congenital agranulocytosis.

PMID- 1381249
TI  - Comparison of microenvironmental CO concentrations in two cities for human
      exposure modeling.
AB  - The microenvironmental components of the CO concentration in two cities are
      compared by subtracting the ambient background concentration from personal
      exposures measured in Denver, Colorado, and Washington, DC. Two surrogate
      measures for the ambient background concentration are tested. Both improve the
      similarity of the means in the two cities, but the Denver standard deviations are
      higher than those in Washington, DC. Microenvironments containing the internal
      combustion engine have both higher means and standard deviations in Denver
      compared with Washington, DC. The Washington, DC, mean concentration for
      automobiles, for example, was 59% of the Denver mean (2.0 ppm versus 4.9 ppm).
      Washington, DC, had approximately 57% of the Denver emissions, and the difference
      in mean CO concentrations is roughly consistent with the lower emissions in
      Washington, DC, due to lower elevation. A surprising finding is that mean CO
      exposure levels caused by cooking with gas stoves in Washington, DC, were only
      58% of the levels in Denver (1.9 ppm and 3.3 ppm, respectively). This result
      suggests that elevation may exert an influence on gas stove emissions that is
      similar to its influence on internal combustion engines. Using an averaging time
      model, analysis of the autocorrelation of sleeping and office microenvironments
      suggests that considerable serial dependency exists. The microenvironmental data
      and findings in this paper have important implications for constructing human
      exposure-activity pattern models. For future human exposure field studies, the
      findings emphasize the importance of measuring background values in a location
      that is extremely close to each microenvironment studied.

PMID- 1381247
TI  - Characterization of the Saccharomyces Golgi complex through the cell cycle by
      immunoelectron microscopy.
AB  - The membrane compartments responsible for Golgi functions in wild-type
      Saccharomyces cerevisiae were identified and characterized by immunoelectron
      microscopy. Using improved fixation methods, Golgi compartments were identified
      by labeling with antibodies specific for alpha 1-6 mannose linkages, the Sec7
      protein, or the Ypt1 protein. The compartments labeled by each of these
      antibodies appear as disk-like structures that are apparently surrounded by small
      vesicles. Yeast Golgi typically are seen as single, isolated cisternae, generally
      not arranged into parallel stacks. The location of the Golgi structures was
      monitored by immunoelectron microscopy through the yeast cell cycle. Several
      Golgi compartments, apparently randomly distributed, were always observed in
      mother cells. During the initiation of new daughter cells, additional Golgi
      structures cluster just below the site of bud emergence. These Golgi enter
      daughter cells at an early stage, raising the possibility that much of the bud's
      growth might be due to secretory vesicles formed as well as consumed entirely
      within the daughter. During cytokinesis, the Golgi compartments are concentrated
      near the site of cell wall synthesis. Clustering of Golgi both at the site of bud
      formation and at the cell septum suggests that these organelles might be directed
      toward sites of rapid cell surface growth.

PMID- 1381250
TI  - Medical treatment for benign prostatic hyperplasia.

PMID- 1381251
TI  - Urinary 5-hydroxyindole acetate concentration in pregnancy induced hypertension.

PMID- 1381252
TI  - Tenascin: a potential modulator of cell-extracellular matrix interactions during
      vertebrate embryogenesis.
AB  - Tenascin is a large oligomeric extracellular matrix (ECM) glycoprotein whose
      expression is highly restricted during vertebrate development. It has a
      characteristic hexameric quaternary structure with six arms linked to a central
      globular domain. Each arm contains a single polypeptide with the central globular
      domain formed by the covalent association of the N-terminal ends of the six
      polypeptides. Tenascin first appears during development, associated with the
      neural crest cell migration pathways of mammalian, avian and amphibian embryos.
      During later development, it is observed at sites of cartilage, bone and tendon
      formation. Tenascin expression also occurs in defined areas in the developing
      nervous system and in condensing mesenchyme, in response to epithelio-mesenchymal
      interactions. The function of tenascin in these different morphogenetic processes
      is not yet clearly understood. Tenascin can promote neurite outgrowth in vitro
      and can inhibit cell interactions with fibronectin. Results based on antibody
      mapping and molecular cloning indicate that these properties involve two distinct
      cell binding sites. Together with its highly regulated expression in the embryo,
      these properties suggest that tenascin plays a key role in the control of cell
      migration and differentiation during development.

PMID- 1381253
TI  - Cloning and sequencing of a 24-kDa Trypanosoma cruzi specific antigen released in
      association with membrane vesicles and defined by a monoclonal antibody.
AB  - In the present study we have used the Tcr7 monoclonal antibody (mAb) previously
      characterized as directed against Trypanosoma cruzi 24-25-kDa specific antigens,
      both are immunogenic in man and during experimental T cruzi infections. We have
      demonstrated that mAb Tcr7 was able to recognize two in vitro translation
      products of molecular weights of 24 and 25 kDa. This suggested the holoproteic
      nature of these two related antigens bearing at least a common epitope and
      allowed us to use Tcr7 for an immunoscreening of a lambda ZAPII T cruzi cDNA
      library. Indeed, we have obtained several positive clones and completely
      sequenced the largest one which encoded theoretically for a protein of 23.7 kDa.
      The sequence analysis revealed a nearly perfect homology between this clone and
      one already described by other investigators and was shown to express a major
      flagellar protein of T cruzi able to bind calcium. Using different overlapping
      peptides derived from the sequence of the cDNA clone, we have localized the
      immunoreactivity of mAb Tcr7 mainly on several primary sequences present in the N
      terminal part of the sequence, suggesting that the mAb could recognize a
      discontinuous epitope. Moreover, the immunoelectron microscopy allowed us to show
      that the antigen(s) carrying the epitope reacting with mAb Tcr7 is (are) released
      in association with membrane vesicles which protruded from the parasite surface
      and the flagellar pocket. This new mechanism of antigen shedding is likely to be
      independent of phospholipase C-mediated release of GPI-anchored molecules.

PMID- 1381254
TI  - Ultrastructural immunodetection of a Pichia anomala killer toxin: a preliminary
      study.
AB  - A monoclonal antibody (mAb KT4), produced against a Pichia anomala killer toxin,
      was used to study the secretion process of toxin producing cells. The indirect
      immunofluorescence assay, performed with large concentrations of mAb KT4, showed
      a homogeneous distribution of the epitope at the cell surface of the P anomala
      cells. When increasing dilutions of mAb KT4 were employed, a 'punctuated'
      labeling appeared on the yeast's cell wall which suggested a heterogeneous
      secretion of the killer toxin. Similar labeling was also observed by
      immunodetection on live yeast cells held in buffered suspension. These results
      confirmed that 'punctuated' labeling was not an artefact due to a distortion of
      the cell's shape by having been dried on glass slides. Indirect immunodetection
      was performed in electron microscopy on ultra-thin sections of cells embedded in
      Araldite resin. The labeling thus obtained showed both the presence of the
      epitope in the cytoplasm and its sensitivity to strong glutaraldehyde fixation.
      Indirect immunodetection, performed on ultra-thin frozen sections, showed a
      cytoplasmic and cell wall labelling. However, the amount of gold particles
      observed in the cell wall was too low to confirm the heterogeneous killer toxin
      secretion observed in immunofluorescence. In this case, killer cells were fixed
      with a low concentration of glutaraldehyde which preserved the structure of the
      epitope complementary with mAb KT4.

PMID- 1381255
TI  - Cellular analysis of the kinetics of alpha-fetoprotein and nuclear oncogene
      activation in primary cultures of adult rat hepatocytes stimulated by epidermal
      growth factor.
AB  - Alpha-fetoprotein (AFP), a fetal gene normally inactivated in quiescent adult
      hepatocytes, is re-expressed in hepatocytes during the proliferating response
      induced by liver regeneration in vivo, or epidermal growth factor (EGF) in vitro.
      The nuclear oncogenes c-jun, c-fos and c-myc are 'immediate early' genes also
      activated during the proliferative response of hepatocytes. Whether AFP gene
      activation is linked to oncogene activation is not known. As a first step in
      answering this question, we have analysed the cellular kinetics of nuclear
      oncogene and AFP gene activation in primary cultures of adult rat hepatocytes
      stimulated by EGF. Gene activation was evaluated at the mRNA level by dot blot
      and in situ hybridization, and at the protein level by immunoperoxidase. C-jun, c
      fos and c-myc mRNA steady state levels in total cellular RNA were increased from
      30 min-2 h after EGF stimulation. In situ hybridization analysis showed that
      transcripts of the three oncogenes increased in all hepatocytes after EGF
      stimulation. While unstimulated cultures did not immunostain for Fos and Myc
      proteins. Fos immunostaining was visible in the majority of hepatocyte nuclei 1
      and 2 h after EGF addition, and Myc cytoplasmic immunostaining of the majority of
      hepatocytes was observed at 2 h of stimulation. AFP mRNA increased in total
      cellular RNA 2 and 4 h after EGF stimulation, with elevated in situ hybridization
      signal for AFP mRNA in all hepatocytes. No hepatocytes immunostained for AFP in
      unstimulated cultures, but a cytoplasmic labeling of 20-30% of the hepatocytes
      was observed 6 h after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381256
TI  - Bombesin-like immunoreactivity in eosinophils. A light and electron microscopic
      study: effect of fixatives and cross-reactivity with various compounds.
AB  - Eosinophils immunopositive for bombesin tetradecapeptide were detected by means
      of light and electron microscopy in human and rat gastrointestinal tract and
      pulmonary tissue. This immunoreaction was only evidenced after the use of acetic
      acid-containing fixative such as Bouin's fluid. The dependence of this
      immunostaining on fixatives and time course were extensively studied. This
      immunoreaction promotes mainly one epitope probably associated with the C
      terminal sequence. This epitope seems also to be present in other neuropeptides
      such as substance P (SP) and, to a lesser extent in chemotactic factors like
      formyl peptide (fMLP) or eosinophil chemotactic factor of anaphylaxis (ECF-A). At
      the electron microscopic level, the immunopositivity was associated with
      eosinophil membranes.

PMID- 1381257
TI  - Do forebrain structures compete for behavioral expression? Evidence from
      amphetamine-induced behavior, microdialysis, and caudate-accumbens lesions in
      medial frontal cortex damaged rats.
AB  - The neurochemical basis of behavioral changes following medial frontal cortex
      damage were investigated. Experiment 1 examined locomotion in response to D
      amphetamine (1.5 and 5 mg/kg) in rats that had received bilateral aspirative
      lesions of the medial frontal cortex alone or in combination with 6
      hydroxydopamine (6-OHDA) lesions of the nucleus accumbens or caudate-putamen.
      Relative to controls, medial frontal cortex rats were initially hypoactive (day 1
      postoperative) but rapidly became hyperactive (days 5-15 postoperative).
      Locomotor-time profiles and stereotypy ratings showed that amphetamine produced a
      selective enhancement of locomotion at the expense of stereotyped behavior.
      Nucleus accumbens lesions blocked the locomotion but enhanced stereotyped
      behavior in the medial frontal cortex damaged rats, suggesting that amphetamine
      enhanced locomotion is dependent upon the integrity of the nucleus accumbens. In
      Experiment 2, intracerebral microdialysis was used to examine whether alterations
      in dopamine (DA) or monoamine metabolites in the nucleus accumbens or caudate
      putamen accompanied the lesion-induced changes in locomotion. There were no
      differences in extracellular DA or monoamine levels between control rats and
      medial frontal cortex rats when tested on day 1 or day 15 postsurgery, either
      when they were at rest, while they walked on a motor-driven belt, or after
      amphetamine treatment. Therefore, it seems unlikely that changes in amphetamine
      induced locomotion following medial frontal cortex lesions are related to
      underlying modifications in dopaminergic activity in the nucleus accumbens. It is
      suggested that neural structures compete for behavioral expression and that
      postlesion behavioral alterations reveal the competitive advantage of remaining
      intact neural systems.

PMID- 1381258
TI  - Competitive interactions during dendritic growth: a simple stochastic growth
      algorithm.
AB  - A simple growth algorithm is presented that deals with one feature of dendritic
      growth, the distance between branches. The fundamental assumption of our growth
      algorithm is that the lengths of dendritic segments are determined by the
      branching characteristics of the growing neurite. Realistic-appearing dendritic
      trees are produced by computer simulations in which it is assumed that: (1)
      growth of individual neurons occurs only at the tips of each growing neurite; (2)
      the growing neurite can either branch (as a bifurcation) or continue to elongate;
      (3) events at any one growing tip do not affect the events at any other growing
      tip; and (4) the probability of branching is a function only of the distance
      grown either from the cell body (if branching has not occurred) or from the
      previous branch point. An analytic solution of a differential equation based on
      these same assumptions produces a distribution of dendritic segment lengths that
      accurately fits an experimentally determined distribution of dendritic segment
      lengths of reconstructed neurons, accounting for about 89% of the sample
      variance. Our analysis indicates that, immediately following branching, the
      temporary suppression of further branching during dendritic growth may be an
      important mechanism for regulating the distance between branches.

PMID- 1381259
TI  - Presence of the binding of a variety of ligands related to ionotropic excitatory
      amino acid receptors in rat retina.
AB  - The binding of [3H]L-glutamic (Glu), [3H](+/-)-3-(2-carboxypiperazin-4-yl)propyl
      1-phosphonic and [3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acids was
      detected in rat retinal membranes extensively washed and treated with a low
      concentration of Triton X-100, in addition to the binding of both [3H]glycine
      (Gly) and [3H]5,7-dichlorokynurenic acid. Furthermore, retinal membranes
      exhibited the binding of [3H](+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imi ne in the presence of Glu, Gly and spermidine
      irrespective of the incubation period employed. Rat retina also contained the
      binding of [3H]kainic acid as well as the binding of [3H]alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid which was sensitive to potentiation by potassium
      thiocyanate. In addition, the binding of both [3H](+)-3-(hydroxyphenyl)-N-(l
      propyl)piperidine and [3H]1,3-di-o-tolyl-guanidine was found in rat retinal
      membranes extensively washed but not treated with Triton X-100. These results
      give support for the proposal that the rodent retina contains subclasses of
      ionotropic brain excitatory amino acid receptors including the N-methyl-D
      aspartate receptor ionophore complex as well as sigma sites.

PMID- 1381260
TI  - Distinct populations of neurons in the ventromedial periaqueductal gray project
      to the rostral ventral medulla and abducens nucleus.
AB  - Following microinjections of a colloidal gold complex into the nucleus
      paragigantocellularis (PGi) of the ventral medulla, and of latex microspheres
      into the nucleus abducens (Abd) of the same animal, retrogradely labeled neurons
      were identified in the region of the contralateral supraoculomotor nucleus (SOM)
      in the ventromedial periaqueductal gray (PAG). Neurons labeled from the Abd were
      found in the SOM in the ventromedial PAG throughout the midbrain, as well as
      scattered ventrally in the oculomotor nucleus. Neurons in the SOM area
      retrogradely labeled from the PGi were most numerous rostral to the dorsal raphe
      nucleus and extended throughout the level of the oculomotor nucleus. Direct
      comparison of the two labels revealed that the neurons that project to the Abd
      were located slightly more ventrally than PGi-projecting neurons. Almost no
      doubly labeled neurons were identified, although singly labeled neurons formed
      adjacent but separate populations. These results indicate that neurons in the SOM
      area projecting to the PGi are distinct from those projecting to the Abd, and
      that the PGi-projecting neurons are probably not pre-oculomotor neurons. Given
      their more dorsal location and the nature of their target neurons in the rostral
      ventrolateral medulla, PGi-projecting neurons may be related to visceromotor, as
      opposed to oculomotor functions.

PMID- 1381261
TI  - TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase.
AB  - Intracerebral hemorrhage occurs in tumors, stroke and head trauma. Proteolysis of
      the extracellular matrix around cerebral capillaries by naturally occurring
      mammalian 72-kDa type IV collagenase may initiate this pathologic event. To
      investigate this hypothesis adult rats underwent intracerebral injection of type
      IV collagenase purified from human melanoma cells. Histologically, at 4 h there
      was perivascular cellular infiltration with hemorrhage, and by 24 h there was
      infarction with necrosis, edema and hemorrhage. Ultrastructurally, the basal
      lamina of endothelial cells was disrupted at 2 h. Brain uptake of [14C]dextran
      and [3H]sucrose increased after intracerebral injection of type IV collagenase
      compared to controls (P less than 0.0001). Tissue inhibitor of metalloproteinase
      2 (TIMP-2) reduced the tracer uptake (P less than 0.02). Metalloproteinase
      inhibitors reduce extracellular matrix proteolysis and protect the blood-brain
      barrier.

PMID- 1381262
TI  - Intracellular electrophysiological and morphological study of the medullary
      inspiratory neurons of the decerebrate rat.
AB  - Intracellular recordings and labelings with horseradish peroxidase (HRP) of
      inspiratory neurons were performed in decerebrate, paralyzed and ventilated rats.
      A total of 58 neurons were located within the ventrolateral medulla. They were
      identified as bulbospinal neurons (n = 15), cranial motoneurons (n = 9) and not
      antidromically activated (NAA) neurons (n = 34) by antidromic stimulation or HRP
      labeling, or both. These inspiratory neurons had rhythmical changes in membrane
      potentials similar to those reported in cats, i.e. an abrupt depolarization at
      the onset of phrenic discharge followed by trajectories of depolarization which
      evolved into augmenting I, bell-shaped I or decrementing I patterns until a rapid
      repolarization at the start of expiration. All types were hyperpolarized during
      expiration by chloride-dependent inhibitory postsynaptic potentials (IPSPs) which
      were demonstrated in 13 neurons from which the reversal was obtained. Such IPSPs
      were apparent in two waves throughout expiration, an early one in post
      inspiration (stage I of expiration) and a late one in late expiration (stage II
      of expiration). These properties are also similar to those of feline inspiratory
      medullary neurons. Four labeled bulbospinal neurons had axonal collaterals which
      were ipsi- and contralateral to the site of their somata. Two of 6 labeled NAA
      neurons exhibited profuse axonal arborizations within various medullary nuclei.
      No medullary axonal collateral was seen from 6 labeled motoneurons. These results
      indicate that even though in the rat a single concentration of inspiratory
      neurons within the ventrolateral medulla has been demonstrated, there is no
      fundamental difference in the organization of the inspiratory neuronal network
      compared to that of the cat.

PMID- 1381264
TI  - Demonstration of a neuronal projection from the entopeduncular nucleus to the
      substantia nigra of the rat.
AB  - The two neuronal tracers, Phaseolus vulgaris leucoagglutinin (PHA-L) and Cholera
      toxin subunit B (CHB) were used in order to study a possible neuronal projection
      from the entopeduncular nucleus to the ventral mesencephalon in the rat. Both
      tracers were identified in brain sections by means of immunohistochemistry. After
      injection of PHA-L in the entopeduncular nucleus PHA-L-positive nerve fibers
      observed in the mesencephalon were moderate in number and mostly restricted to
      the mediodorsal part of the substantia nigra, pars reticulata. In addition, a low
      number of PHA-L-immunoreactive nerve fibers was found in the substantia nigra,
      pars compacta, the rostral part of the ventral tegmental area, and in the deep
      mesencephalic nucleus. In agreement with these observations, several labeled
      neurons were observed in the ipsilateral entopeduncular nucleus after injections
      of CHB in the substantia nigra. These results indicate the presence of a direct
      neuronal projection between the two major output channels of the basal ganglia.

PMID- 1381263
TI  - Blockade of acute hypertensive response does not prevent changes in behavior or
      in CSF acetylcholine (ACH) content following traumatic brain injury (TBI).
AB  - There is evidence that the blood-brain barrier (BBB) is breached following
      traumatic brain injury (TBI), allowing the unregulated entry of circulating
      neuroactive substances into the central nervous system. As the traumatic episode
      is typically associated with an acute hypertensive event, which in itself may
      alter BBB status, the effects of the blockade of TBI-associated hypertension on
      injury-associated behavioral and cerebrospinal fluid (CSF) neurochemical changes
      were assessed in rats. Animals were injected with either saline or hexamethonium
      15 min prior to a moderate fluid percussion injury while under light
      methoxyflurane anesthesia. This dose of hexamethonium was demonstrated to block
      the hypertensive response to TBI. Pretreatment with hexamethonium prevented
      neither acute nor more enduring behavioral deficits observed after TBI.
      Hexamethonium did not prevent TBI-associated increases in CSF acetylcholine (ACh)
      content in separate group of rats sampled 12 min following TBI. Furthermore,
      histological inspection indicated that hexamethonium did not prevent TBI-induced
      disruption of the BBB, as assessed by intravascular horseradish peroxidase (HRP).
      Thus, blockade of the hypertensive response to TBI does not afford behavioral
      protection nor does it prevent changes in the BBB or CSF ACh content following
      TBI. TBI is in itself sufficient to modify behavior, neurochemistry and BBB
      function in the absence of hypertension.

PMID- 1381265
TI  - AMPA glutamate receptor activation in the posterior zona incerta inhibits
      amphetamine- and apomorphine-induced stereotypy.
AB  - Previous work demonstrated that alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) glutamate receptor antagonism in the zona incerta (ZI)
      dorsal to the subthalamic nucleus inhibits stereotypy in rats. The current
      investigation was undertaken to determine if AMPA receptors in a more caudal
      portion of the ZI have a role in the expression of stereotyped behavior. Rats
      were injected bilaterally with AMPA into the posterior ZI dorsal to the
      substantia nigra, and immediately given a systemic injection of d-amphetamine (10
      mg/kg, s.c.) or apomorphine (1 mg/kg s.c.). AMPA produced a dose-dependent
      inhibition of stereotypy induced by both drugs which was prevented by the
      coadministration of the AMPA/kainic acid antagonist, 6,7-dinitroquinoxaline-2,3
      dione (DNQX) (0.5 microgram/0.5 microliter). A dose of AMPA as low as 62.5 ng
      completely abolished the oral component of stereotypy induced by both apomorphine
      and amphetamine. This dose of AMPA alone had no significant effect on spontaneous
      locomotor activity but enhanced the locomotor response stimulated by amphetamine
      (10 mg/kg, s.c.) due to an inhibition of stereotypy. The finding that activation
      of AMPA receptors in the posterior ZI inhibits stereotypy shows a contrast to
      results in the neighboring medial ZI dorsal to the subthalamic nucleus, where
      blockade of AMPA/kainic acid glutamate receptors with DNQX inhibits stereotypy.

PMID- 1381266
TI  - Mechanotransducing ion channels in astrocytes.
AB  - Ion channels present on the soma of neonatal rat astrocytes in primary cell
      culture were studied using the single channel recording technique. Ion channels
      were activated by changing the pressure in the back of the pipette. The
      morphological structure of the patch membrane was examined while recording
      channel activity. One class of channel was activated by increasing the pipette
      pressure (curvature-sensitive or CS channels). CS channels were observed in 150
      mM KCl, 150 mM NaCl, or 150 mM sodium gluconate. At constant pressure the closed
      times decreased with depolarization. CS channels had a conductance of 50 pS in
      150 mM NaCl, and displayed an inwardly rectifying current-voltage relationship.
      CS channel activity was found only in cell-attached patches, and were active only
      when the patch membrane curved towards the soma. The other class of channel was
      found to be activated by both suction and pressure (stretch-activated or SA
      channels). Four SA conductance levels were found: 360, 230, 144, and 70 pS in 150
      mM KCl. Each conductance displayed a linear current-voltage relationship. At
      negative membrane potentials SA channels were inhibited by Cs+, Ba2+ or Na+. The
      relationship between average mechanosensory current and pressure was biphasic for
      SA channels and monophasic for CS channels. Combinations of SA and CS channels
      could be observed in the same patch. We propose that CS channels are non-specific
      cation channels which sense membrane tension only when the patch membrane is in a
      specific, permissive curvature. SA channels appear to be K(+)-selective channels
      that sense membrane tension independent of the direction of curvature.

PMID- 1381267
TI  - Guanethidine sympathectomy increases substance P concentration in the superior
      sympathetic ganglion of adult rats.
AB  - Adult rats received intraperitoneal injections of guanethidine or saline for 5
      weeks. Six to 8 weeks following completion of treatment, concentrations of
      substance P and neuropeptide Y (NPY) were measured by radioimmunoassay in the
      superior cervical ganglion (SCG) and thoracic spinal cord. The SCG was also
      immunostained for NPY and substance P. No differences were observed in thoracic
      spinal cord content of either NPY or substance P. We observed depletion of NPY
      immunoreactive neurons and NPY levels in the SCG, and pharmacologic evidence of
      postganglionic denervation in guanethidine-treated rats. In guanethidine-treated
      rats, there was a marked increase of substance P levels in the SCG, where
      substance P was localized in fibers, but not cell bodies. Thus, sprouting of
      substance P-containing sensory fibers in the sympathetic ganglia occurs following
      postganglionic sympathectomy in adult rats.

PMID- 1381268
TI  - Serum alpha-L-fucosidase. A useful marker in the diagnosis of hepatocellular
      carcinoma.
AB  - BACKGROUND AND METHODS: The value of serum alpha-L-fucosidase activity in the
      diagnosis of hepatocellular carcinoma (HCC) was investigated by determining the
      enzyme activity levels in 21 patients with HCC, 76 patients with cirrhosis, 22
      patients with other malignant neoplasms, and 23 healthy subjects. RESULTS: The
      serum alpha-L-fucosidase activity level in patients with HCC (575.76 +/- 212.86
      nmol/ml/h) was significantly higher than that found in patients with cirrhosis
      (274.55 +/- 138.97 nmol/ml/h; P less than 0.001) or other neoplasms (257.91 +/-
      128.12 nmol/ml/h; P less than 0.001) and in controls (221.23 +/- 114.45
      nmol/ml/h; P less than 0.001). No significant differences were found between
      controls and patients with cirrhosis and between controls and patients with other
      malignant neoplasms. When 443 nmol/ml/h is taken as the cutoff value (mean value
      of controls plus 2 standard deviations), alpha-L-fucosidase sensitivity and
      specificity were 76% and 90.9%, respectively. CONCLUSIONS: These results suggest
      that alpha-L-fucosidase is a useful marker for detecting HCC, in conjunction with
      alpha-fetoprotein and ultrasonography.

PMID- 1381269
TI  - A comparative immunohistochemical study of jejunoileal and appendiceal
      carcinoids. Implications for histogenesis and pathogenesis.
AB  - BACKGROUND: The purpose of this study was to determine the histogenesis of
      jejunoileal and appendiceal carcinoids and to ascertain whether this could be
      useful in further explaining the pathology of these neoplasms. METHODS: Eight
      cases each of multiple jejunoileal carcinoids and appendiceal carcinoids together
      with their respective age-matched and sex-matched controls were stained with
      silver stains, chromogranin A, serotonin, and S-100. Histomorphometric
      evaluations of the endocrine cells in the mucosa adjacent to the carcinoids were
      carried out and compared with the respective controls using the Student's t test.
      RESULTS: All the carcinoids from both groups stained for argyrophilia,
      argentaffinity, chromogranin A, and serotonin. Histomorphometric evaluations
      showed intraepithelial endocrine cell hyperplasia (IECH) in the jejunoileal
      carcinoid group (P = 0.007, chromogranin; P = 0.004, serotonin) but not in the
      appendiceal carcinoid group. On the other hand, subepithelial endocrine cell
      aggregates that were separate from the main tumor were seen in two cases of
      appendiceal carcinoids. With S-100, all appendiceal carcinoids showed intrinsic
      tumor positivity whereas the jejunoileal carcinoids did not. CONCLUSIONS: The
      finding of IECH with multiple jejunoileal carcinoids suggests that these
      carcinoids arise from a field effect. The absence of IECH with appendiceal
      carcinoids as well as their association with subepithelial endocrine cell
      aggregates and their intimate relationship with Schwann cell processes suggests
      that appendiceal carcinoids arise from a more discrete unit, the subepithelial
      neuroendocrine complex.

PMID- 1381270
TI  - Immunohistochemical identification of tissue factor in solid tumors.
AB  - Patients with cancer experience a much higher than expected incidence of
      thromboembolic disorders, commonly referred as Trousseau syndrome. Although this
      association has been well documented, the etiology of the hypercoagulable state
      is not known. The expression on tumor cells of tissue factor (TF), a membrane
      bound lipoprotein that functions as a cofactor to factor VIIa in the initiation
      of the extrinsic pathway of blood coagulation, has been postulated as a possible
      mechanism. Whereas the distribution of TF in normal tissues is known, no large
      survey of TF expression in malignant tissues has been reported. In this study a
      polyclonal, monospecific rabbit anti-human TF IgG was used for
      immunohistochemical localization of TF antigen in 85 different tumor specimens.
      In general, cell types which normally express TF continued to do so after
      malignant transformation (41 of 60 epithelial tumor specimens were positive for
      TF). Tumors of nonepithelial origin frequently lacked TF, with only 3 of 19
      specimens containing evidence of TF antigen. In addition five of six benign
      tumors did not express TF. Many tumor types commonly associated with Trousseau
      syndrome, for example lung, pancreatic, breast, colon and gastric carcinomas,
      stained positively for TF. Based on this survey, it appears that TF expression by
      tumors may be an important factor in the pathogenesis of a hypercoagulable state
      in some patients with cancer.

PMID- 1381271
TI  - Serum CA 19-9 and alpha-fetoprotein levels in primary hepatocellular carcinoma
      and liver cirrhosis.

PMID- 1381273
TI  - Induction of intercellular adhesion molecule 1 on small cell lung carcinoma cell
      lines by gamma-interferon enhances spontaneous and bispecific anti-CD3 x
      antitumor antibody-directed lymphokine activated killer cell cytotoxicity.
AB  - The interaction between LFA-1 and its natural ligand, ICAM-1, plays an important
      role in leukocyte adhesion and signal transduction. LFA-1-mediated T-cell
      adhesion is generally activated by CD3-mediated signal in association with T-cell
      receptor-mediated recognition of the antigen/major histocompatibility complex on
      antigen-presenting cells. In the present study, we compared spontaneous or
      bispecific antibody (BsAb)-directed LAK cell cytotoxicity against ICAM-1+ or ICAM
      1- small cell lung cancer (SCLC) cell lines. gamma-Interferon (IFN-gamma)-induced
      ICAM-1 expression on ICAM-1- SCLC cell lines, and susceptibility to LAK cells was
      increased simultaneously. Increased cytolysis of the IFN-gamma-treated SCLC was
      inhibited by an anti-ICAM-1 monoclonal antibody (mAb). Furthermore, LAK cell
      cytotoxicity directed by BsAb, which was composed of OKT3 and anti-SCLC mAb, was
      also increased by the IFN-gamma treatment of SCLC, and this increase was
      inhibited by an anti-ICAM-1 mAb but not by anti-Class I or anti-CD2 mAb. These
      results suggest that a prior administration of IFN-gamma would enhance the
      efficacy of the following specific targeting therapy utilizing BsAb and LAK cells
      by up-regulating the ICAM-1 expression on tumor target cells. The combinational
      use of IFN-gamma and anti-CD3 x anti-tumor BsAb might be a promising way of
      enhancing LAK cell-mediated adoptive immunotherapy in small cell lung cancer
      patients.

PMID- 1381272
TI  - A novel Arg-Gly-Asp containing peptide specific for platelet aggregation and its
      effect on tumor metastasis: a possible mechanism of RGD peptide-mediated
      inhibition of tumor metastasis.
AB  - A novel cyclic tetrapeptide containing L-arginine-glycine-L-aspartic acid-L
      phenylglycine (cyclo-RGDPhg) was synthesized and found to be a potent inhibitor
      of platelet aggregation induced by highly metastatic murine squamous cell
      carcinoma (SCCVII) cells (IC50 = 3.3 microM) as well as ADP (1.5 microM). This
      cyclic peptide, however, showed similar or less inhibitory activities on adhesion
      of SCCVII cells to fibronectin, vitronectin and type IV collagen as compared with
      those of parent linear tetrapeptide, RGDS. These results show that cyclo-RGDPhg
      peptide is a highly specific antagonist for gpIIb/IIIa on platelets. Moreover,
      this peptide failed to suppress pulmonary metastasis of SCCVII cells in an
      experimental metastasis model. These results indicate that RGD peptide-mediated
      inhibition of tumor metastasis is attributed to the suppression of cell adhesion
      but not platelet aggregation. These also suggest that platelet aggregation is not
      an essential step during blood circulation of tumor cells for the completion of
      metastasis.

PMID- 1381274
TI  - A new tumor-associated antigen useful for serodiagnosis of hepatocellular
      carcinoma, defined by monoclonal antibody KM-2.
AB  - After immunization of mice with the human hepatocellular carcinoma (HCC) cell
      line PLC/PRF/5, we produced monoclonal antibody KM-2, which allowed us to
      characterize a new HCC-associated antigen (KM-2 antigen) and to develop a
      sandwich-type radioimmunoassay. The KM-2 antigen was strongly expressed on the
      cell surface of HCC cell lines. Immunofluorescence staining of frozen sections of
      different tissues and tumors confirmed its specific expression on the cell
      surface of a group of HCC. The antigen was also detected in the bile canaliculi
      of normal liver. Its biochemical characterization revealed a high molecular
      weight (M(r) approximately 900,000) glycoprotein with an N-linked carbohydrate
      chain close to the peptide epitope recognized by the KM-2 monoclonal antibody. By
      the radioimmunoassay for the KM-2 antigen, the antigen was detected in sera of 72
      (47%) of 154 patients with HCC and 3 (3%) of 102 patients with liver cirrhosis;
      it was not detected in 96 patients with chronic hepatitis or in 100 healthy
      control individuals. The positive rate of KM-2 antigen (72 of 154, 47%) was
      significantly (P less than 0.01) higher than that (51 of 154, 33%) of alpha
      fetoprotein (AFP) when the cut-off level of AFP was taken as the widely accepted
      400 ng/ml. No significant correlation was recognized between serum levels of the
      KM-2 antigen and AFP (r = 0.15; P greater than 0.05). In addition, among 103
      patients with HCC whose AFP levels were less than 400 ng/ml, 31 (30%) were
      positive for the KM-2 antigen. Determination of the serum KM-2 antigen would be
      useful for the serodiagnosis of patients with HCC, particularly in cases with
      normal or low AFP levels.

PMID- 1381275
TI  - Acidic fibroblast growth factor-Pseudomonas exotoxin chimeric protein elicits
      antiangiogenic effects on endothelial cells.
AB  - It has recently been shown that chimeric toxins composed of acidic fibroblast
      growth factor fused to mutant forms of Pseudomonas exotoxin (aFGF-PE) are
      cytotoxic to a variety of tumor cell lines with FGF receptors. Although aFGF-PE
      might be considered as a possible chemotherapeutic toxin, limited knowledge is
      available concerning its effect on endothelia. This study investigates whether
      one of the aFGF-PE fusion proteins, aFGF-PE664GluKDEL, can function as an anti
      angiogenic agent. Protein synthesis studies using rat epididymal fat pad
      microvascular endothelial cells (RFCs) indicated that after 24 h in culture, aFGF
      PE had a significant inhibitory effect on protein synthesis at concentrations
      greater than 100 ng/ml. In cultures incubated with 1000 ng/ml aFGF-PE, RFC
      protein synthesis was inhibited as much as 83%. RFCs were also cultured in a 3
      dimensional type I collagen gel and incubated with either transforming growth
      factor beta 1, aFGF-PE, or a combination of both. Transforming growth factor beta
      1 elicits in vitro angiogenesis in these 3-dimensional cultures which consist of
      rapid formation of complex tubular structures. Transforming growth factor beta 1
      treated RFCs incubated with aFGF-PE were unable to produce this angiogenic
      response, nor were they able to migrate out of the 3-dimensional culture to form
      a monolayer as shown by controls. Cell viability analyses showed that aFGF-PE
      produced a dose-dependent toxic effect which ranged from 10 to 90% cell death.
      Competition assays in which the chimeric toxin was preincubated with antibodies
      to aFGF resulted in an 89% reversal of the inhibitory effects of aFGF-PE on
      endothelial cells. Acidic FGF-PE with a mutation in the ADP ribosylation domain
      of PE was inactive in both 2-dimensional and 3-dimensional cultures. These data
      show that aFGF-PE has specific in vitro cytotoxic, antiangiogenic, and
      antimigratory effects on microvascular endothelia.

PMID- 1381276
TI  - Inhibition of angiogenesis by suramin.
AB  - In this study, we have determined the ability of suramin to inhibit angiogenesis
      in the chick chorioallantoic membrane. Suramin alone showed significant
      angiostatic activity in a dose-related manner. Suramin also potentiated the
      activity of the angiostatic steroids, cortisol-21-phosphate, 17 alpha
      hydroxyprogesterone, tetrahydrocortisol, and tetrahydrocortexolone. The presence
      of heparin decreased the angiostatic activity of suramin. These results suggest
      that suramin may decrease tumor growth by inhibiting angiogenesis. These novel
      findings indicate that suramin, perhaps in combination with angiostatic steroids,
      may be the basis for important new therapeutic approaches for diseases of
      neovascularization.

PMID- 1381277
TI  - IGFBP-3 gene expression and estrogen receptor status in human breast carcinoma.
AB  - Insulin-like growth factors (IGF) I and II are potent mitogens for breast
      carcinoma proliferation. IGF-mediated proliferative activity can be markedly
      enhanced by the presence of specific IGF-binding proteins (IGFBPs). IGFBP-3 has
      been shown to enhance IGF-mediated growth in a number of systems. Studies have
      demonstrated IGFBP-3 secretion only in estrogen receptor (ER)-negative breast
      carcinoma cell lines while IGFBP-3 could not be detected in media conditioned by
      ER-positive cell lines. We investigated whether a relationship exists between ER
      status and IGFBP-3 mRNA expression in human breast carcinoma biopsy specimens. We
      have detected IGFBP-3 mRNA in breast carcinoma tissue obtained from patients
      utilizing in situ hybridization. Quantitation of IGFBP-3 mRNA levels was
      performed utilizing image cytometry. There was a significantly higher expression
      of IGFBP-3 mRNA in ER-negative breast carcinoma specimens when compared to the ER
      positive specimens. Whether this higher expression of IGFBP-3 mRNA and presumed
      secretion of IGFBP-3 by ER-negative tumors play a role in the rapid proliferation
      and poor prognosis of these tumors remains to be determined.

PMID- 1381278
TI  - The use of porcine liver (2----3)-alpha-sialyltransferase in the large-scale
      synthesis of alpha-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-D-GlcpNAc, the epitope
      of the tumor-associated carbohydrate antigen CA 50.
AB  - alpha-Neup5Ac-(2----3)-beta-D-Galp-(1----3)-D-GlcpNAc (2) and, alpha-Neup5Ac-(2--
      -3)-beta-D-Galp-(1----3)-beta-D-GlcpNAcOMBn+ ++ were prepared on a large scale by
      the action of beta-D-Galp-(1----3)-D-GalpNAc (2----3)-alpha-sialyltransferase
      (partially purified from porcine liver) on beta-D-Galp-(1----3)-D-GlcpNAc and
      beta-D-Galp-(1----3)-beta-D-GlcpNAcOMBn, respectively. The trisaccharide 2 is the
      epitope of the tumor-associated carbohydrate antigen CA 50, highly expressed in
      human pancreatic adenocarcinoma.

PMID- 1381279
TI  - Further definition of the size of the blood group-i antigenic determinant using a
      chemically synthesised octasaccharide of poly-N-acetyllactosamine type.
AB  - In earlier studies, the minimum structure which inhibited the binding of anti-i
      to an i-active glycoprotein was the linear trisaccharide, beta-D-Galp-(1----4)
      beta-D-GlcpNAc-(1----3)-D-Gal. There was an increasing hierarchy of inhibitory
      activities in the linear tetrasaccharide, beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1-
      --3)-beta-D-Galp-(1----4)-beta-D -GlcNAc , its methyl beta-glycoside, and in the
      methyl beta-glycoside of the hexasaccharide. The linear octasaccharide methyl
      beta-glycoside in this series is approximately only half as active as the
      hexasaccharide methyl beta-glycoside. Analyses by high resolution 1H-n.m.r. of
      these two oligosaccharides indicated that they have similar conformations in
      solution, and there is no evidence for the occurrence of inter-molecular
      interactions which might partially hinder the binding of anti-i to the
      octasaccharide methyl beta-glycoside. These results are consistent with the size
      of the i antigen being in the region of a hexasaccharide. It is proposed that the
      methyl aglycon group of the hexasaccharide methyl beta-glycoside confers an above
      normal activity by presenting a hydrophobic area for additional contact in the
      vicinity of the antibody-combining site.

PMID- 1381280
TI  - The structure of O-specific polysaccharide from Pseudomonas solanacearum ICMP
      4157.

PMID- 1381281
TI  - Synthesis of allyl 6-O-(3-deoxy-alpha- and -beta-D-manno-oct-2- ulopyranosylonic
      acid)-(1----6)-2-deoxy-2-[(3R)-3-hydroxytetradecanamido]- beta-D-glucopyranoside
      4-phosphate and of the copolymer of the alpha anomer with acrylamide.
AB  - The title disaccharides were synthesized by mercuric cyanide-catalyzed
      condensation of methyl (4,5,7,8-tetra-O-acetyl-3-deoxy-alpha-D-manno-oct-2
      ulopyranosyl bromide)onate and allyl 2-[(3R)-3-acetoxy-tetradecanamido]-3-O
      benzyl-2-deoxy-beta-D- glucopyranoside, followed by phosphorylation of the
      alcoholic function of the amino sugar. The phosphorylated anomers were separated
      by chromatography and deprotected by conventional methods. Polymeric material was
      obtained by copolymerisation, catalyzed by peroxosulphate and N,N,N',N'
      tetramethylethylenediamine, of the alpha anomer with acrylamide; it contained ca.
      one disaccharide unit for 18 acrylamide residues.

PMID- 1381282
TI  - Synthesis of 1-deoxynojirimycin-containing glycans related to the Lewis X and
      sialyl-Lewis X epitopes recognized by LEC-CAMs.

PMID- 1381283
TI  - Stereoselective syntheses of a di-, tri-, and tetra-saccharide fragment of
      Shigella dysenteriae type 1 O-antigen using 3,4,6-tri-O-acetyl-2-azido-2-deoxy
      alpha-D-glucopyranosyl chloride as a glycosyl donor.
AB  - Methyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranoside (1) furnished a crystalline 3-O
      bromoacetyl derivative that was treated with the dichloromethyl methyl ether
      ZnCl2 reagent to give 2,4-di-O-benzoyl-3-O-bromoacetyl-alpha-L-rhamnopyranosyl
      chloride (3). Compounds 1 and 3 were condensed under the conditions of base
      deficient, silver trifluoromethanesulfonate-mediated glycosylation to give a
      fully protected rhamnobioside, which on O-debromoacetylation afforded the
      disaccharide nucleophile 10. Similar condensation of 3 with methyl 3-O-benzoyl
      4,6-O-benzylidene-alpha-D-galactopyranoside, followed by O-debromoacetylation and
      condensation of the thus formed methyl O-(2,4-di-O-benzoyl-alpha-L
      rhamnopyranosyl)-(1----2)-4,6-O-benzylidene- 3-O-benzoyl-alpha-D
      galactopyranoside again with 3, gave the trisaccharide glycoside. Subsequent O
      debromoacetylation gave 17, having only HO-3(3) unsubstituted. Silver perchlorate
      mediated glycosylations of 1, 10, and 17 with 3,4,6-tri-O-acetyl-2-azido-2-deoxy
      alpha-D-glucopyranosyl chloride afforded, with high alpha stereoselectivity,
      protected di-, tri-, and tetra-saccharide glycosides. Subsequent hydrogenation,
      followed by N-acetylation and O-deacylation, afforded three oligosaccharide
      glycosides having nonreducing terminal 2-acetamido-2-deoxy-alpha-D-glucopyranosyl
      residues and comprising successively larger portions of the repeating unit of
      Shigella dysenteriae type 1 O-antigen.

PMID- 1381284
TI  - Protein synthesis in pulmonary, cardiac, and skeletal muscle in acute
      hypertension induced by aortic constriction in the rat.
AB  - OBJECTIVE: The aim was to investigate nucleic acid composition and rates of
      protein synthesis in cardiopulmonary tissues and skeletal muscle in response to
      hypertension induced by aortic constriction. METHODS: After five days of
      abdominal aortic constriction, protein, RNA, and DNA contents were measured in
      the lung, the left and right atria, the left and right ventricles, and
      gastrocnemius muscle from young male Wistar rats weighing 120-140 g. Rates of
      protein synthesis were also measured in these tissues with L[4-3H]phenylalanine.
      RESULTS: Aortic constriction significantly increased the right atrial weight and
      in contrast reduced the lung weight, compared to pair fed and sham operated
      controls. The wet weights of all other tissues were unaffected. The
      concentrations of right atrial proteins, RNA, and DNA were also significantly
      reduced though total protein, RNA, and DNA contents were unaltered. The left
      ventricular RNA concentration increased and there were variable alterations in
      protein and DNA composition. The protein, RNA, and DNA compositions of the other
      tissues showed patterned responses, which included reductions in lung and
      skeletal muscle DNA concentrations, reductions in the skeletal muscle RNA/DNA
      ratio, and a decrease in the lung protein/DNA ratio. In response to aortic
      constriction there were increases in the left ventricular fractional rate of
      protein synthesis in mixed, high salt (myofibrillar), and low salt (sarcoplasmic)
      fractions. Rates of protein synthesis in all other regions of the heart, lung and
      skeletal muscle were not significantly changed. CONCLUSIONS: We conclude that in
      abdominal aortic constriction, the left ventricles display early adaptive
      responses without any concomitant change in mass. Those regions of the rat
      cardiopulmonary system which are not directly exposed to the acute pressure
      overloading, ie, right atrium, lungs, and skeletal muscle, also show
      disturbances.

PMID- 1381285
TI  - Nitric oxide, a novel biologic messenger.

PMID- 1381286
TI  - New reactions catalyzed by a group II intron ribozyme with RNA and DNA
      substrates.
AB  - Here we describe three novel reactions of the self-splicing group II intron bI1
      (the first intron of the COB gene of yeast mitochondria) demonstrating its
      catalytic versatility: reversal of the first step of the self-splicing reaction
      catalyzed by a linear form of the intron utilizing the energy of a
      phosphoanhydride bond for transesterification, ligation of a single-stranded DNA
      to an RNA, and cleavage of a single-stranded DNA substrate. These results have
      the following evolutionary implications: use of the alpha-beta bond of a terminal
      triphosphate for transesterification suggests that an RNA RNA replicase could use
      mononucleotide triphosphates as precursors, and cleavage of single-stranded DNA
      and DNA-RNA ligation suggests that excised group II introns might integrate
      directly into DNA without prior reverse transcription.

PMID- 1381287
TI  - The genetic basis of epidermolytic hyperkeratosis: a disorder of differentiation
      specific epidermal keratin genes.
AB  - Epidermolytic hyperkeratosis (EH) is a skin disease characterized by keratin
      filament clumping and degeneration in terminally differentiating epidermal cells.
      We have discovered that the genetic basis for EH resides in mutations in
      differentiation-specific keratins. Two of six distinct incidences of EH had a
      keratin 10 (K10) point mutation in a highly conserved arginine. Remarkably, this
      same residue is mutated in the basal epidermal K14 in three incidences of another
      skin disease, epidermolysis bullosa simplex (EBS). By genetic engineering, gene
      transfection, and 10 nm filament assembly, we show that this mutation is
      functionally responsible for the keratin filament clumping that occurs in basal
      (EBS) or suprabasal (EH) cells. These studies strengthen the link between
      filament perturbations, cell fragility, and degeneration first established with
      EBS. They also suggest a correlation between filament disorganization and either
      cytokinesis or nuclear shape, giving rise to the seemingly binucleate cells
      typical of EH.

PMID- 1381288
TI  - A leucine----proline mutation in the H1 subdomain of keratin 1 causes
      epidermolytic hyperkeratosis.
AB  - Epidermolytic hyperkeratosis is an autosomal dominant disorder affecting the
      structural integrity of the suprabasal layers of human epidermis. We have
      recently documented in one family linkage of the disease phenotype to the cluster
      of type II keratins. We have now identified a leucine----proline amino acid
      substitution in the conserved H1 subdomain of keratin 1 that is present only in
      affected family members. Using a quantitative assay and electron microscopy with
      synthetic peptides, we show that, whereas the wild-type H1 peptide rapidly
      disassembles preformed keratin filaments in vitro, the mutant peptide does this
      far less efficiently. Therefore the mutation in keratin 1 is likely to cause
      defective keratin filaments and hence a defective cytoskeleton in the epidermal
      cells in vivo.

PMID- 1381289
TI  - Derivation of pluripotential embryonic stem cells from murine primordial germ
      cells in culture.
AB  - Steel factor (SF) and LIF (leukemia inhibitory factor) synergistically promote
      the proliferation and survival of mouse primordial germ cells (PGCs), but only
      for a limited time period in culture. We show here that addition of bFGF to
      cultures in the presence of membrane-associated SF and LIF enhances the growth of
      PGCs and allows their continued proliferation beyond the time when they normally
      stop dividing in vivo. They form colonies of densely packed, alkaline phosphatase
      positive, SSEA-1-positive cells resembling undifferentiated embryonic stem (ES)
      cells in morphology. These cultures can be maintained on feeder layers for at
      least 20 passages, and under appropriate conditions give rise to embryoid bodies
      and to multiple differentiated cell phenotypes in monolayer culture and in tumors
      in nude mice. PGC-derived ES cells can also contribute to chimeras when injected
      into host blastocysts. The long-term culture of PGCs and their reprogramming to
      pluripotential ES cells has important implications for germ cell biology and the
      induction of teratocarcinomas.

PMID- 1381290
TI  - An immunofluorescence study of the effects of ultraviolet radiation on the
      organization of microfilaments, keratin intermediate filaments, and microtubules
      in human keratinocytes.
AB  - Indirect immunofluorescence microscopy has been used to investigate the
      ultraviolet (UV) radiation induced disruption of the organization of
      microfilaments, keratin intermediate filaments, and microtubules in cultured
      human epidermal keratinocytes. Following irradiation, concurrent changes in the
      organization of the three major cytoskeletal components were observed in cells
      incubated under low Ca2+ (0.15 mM) conditions. UV irradiation induced a dose
      dependent condensation of keratin filaments into the perinuclear region. This
      collapse of the keratin network was accompanied by the reorganization of
      microfilaments into rings and a restricted distribution of microtubules,
      responses normally elicited by exposure to high Ca2+ (1.05 mM) medium. The UV
      induced alteration of the keratin network appears to disrupt the interactions
      between keratin and actin, permitting the reorganization of actin filaments in
      the absence of Ca2+ stimulation. In addition to the perinuclear condensation of
      keratin filaments, UV irradiation inhibits the Ca2+ induced formation of keratin
      alignments at the membrane of apposed cells if UV treatment precedes exposure to
      high Ca2+ medium. Incubation of keratinocytes in high Ca2+ medium for 24 hours
      prior to irradiation results in the stabilization of membrane associated keratin
      alignments and a reduced susceptibility of cytoplasmic keratin filaments to UV
      induced disruption. Unlike results from investigations with isogenic skin
      fibroblasts, no UV induced disassembly of microtubules was discernible in
      irradiated human keratinocytes.

PMID- 1381291
TI  - Expression of cystic fibrosis transmembrane regulator Cl- channels in heart.
AB  - Cyclic AMP (cAMP)-dependent chloride channels modulate changes in resting
      membrane potential and action potential duration in response to autonomic
      stimulation in heart. A growing body of evidence suggests that there are marked
      similarities in the properties of the cAMP-dependent chloride channels in heart
      and cystic fibrosis transmembrane regulator (CFTR) chloride channels found in
      airway epithelia or in cells expressing the CFTR gene product. We isolated poly
      A+ mRNA from rabbit ventricle and converted it to cDNA for amplification using
      the polymerase chain reaction (PCR). A fragment corresponding to the nucleotide
      binding domain 1 (NBD1) of the CFTR transcript was cloned. Comparison of the
      amino acid sequence of NBD1 of human CFTR with the deduced sequence of the rabbit
      heart PCR product indicated 98% identity. Northern blot analysis, using the heart
      amplification product as a cDNA probe, demonstrated expression of homologous
      transcripts in human atrium, guinea pig and rabbit ventricle, and dog pancreas.
      Xenopus oocytes injected with poly A+ mRNA extracted from rabbit and guinea pig
      ventricle or dog pancreas expressed robust time-independent chloride currents in
      response to an elevation of cAMP. We conclude that CFTR chloride channels are
      expressed in heart and are responsible for the observed cAMP-dependent chloride
      conductance.

PMID- 1381292
TI  - Thrombin receptor 14-amino acid peptide mediates endothelial hyperadhesivity and
      neutrophil adhesion by P-selectin-dependent mechanism.
AB  - Thrombin cleaves its receptor at arginine-41, resulting in the generation of a
      new receptor NH2-terminus with the sequence SFLLRNPNDKYEPF. This peptide (TRP-14)
      may signal a variety of thrombin's responses. We examined the effects of TRP-14
      in inducing endothelial cell hyperadhesivity and neutrophil (PMN) adhesion to
      endothelial cell monolayers. Human umbilical vein endothelial cells (HUVECs)
      challenged with TRP-14 (10(-4) to 10(-5) M) produced concentration-dependent
      increases in endothelial adhesivity to PMN. In contrast, position 1 to 2 inverted
      peptide (FSLLRNPNDKYEPF) did not induce the response. The adhesion response was
      transient; that is, PMN adhesion increased within 15 minutes and decreased by 75
      minutes after TRP-14 challenge of HUVECs. The transient endothelial adhesiveness
      paralleled the time course of P-selectin expression. TRP-14-induced release of P
      selectin from intracellular stores may be a critical determinant of the response
      since treatment of endothelial cells with anti-P-selectin monoclonal antibody
      (mAb) G1 prevented the increase in PMN adhesion. Control nonneutralizing anti-P
      selectin mAb S12 and mAb RR1/1 directed against intercellular adhesion molecule-1
      (ICAM-1) on HUVECs were ineffective. The results indicate that the "tethered
      ligand" of the thrombin receptor created by the proteolytic action of thrombin on
      its receptor (i.e., TRP-14) signals increased endothelial adhesiveness by a P
      selectin-dependent mechanism. Thrombin-induced PMN adhesion may involve formation
      of a new NH2-terminus of the endothelial thrombin receptor with the sequence
      SFLLRNPNDKYEPF followed by activation of endothelial second messenger pathways
      and the transient expression of P-selectin.

PMID- 1381293
TI  - Ionic currents in single smooth muscle cells of the canine renal artery.
AB  - Membrane currents from single smooth muscle cells enzymatically isolated from
      canine renal artery were recorded using the patch-clamp technique in the whole
      cell and cell-attached configurations. These cells exhibited a mean resting
      potential, input resistance, membrane time constant, and cell capacitance of 
      51.8 +/- 2.1 mV, 5.2 +/- 0.98 G omega, 116.2 +/- 16.4 msec, and 29.1 +/- 2.0 pF,
      respectively. Inward current, when elicited from a holding potential of -80 mV,
      activated near -50 mV, reached a maximum near 0 mV and was sensitive to the
      dihydropyridine agonist Bay K 8644 and dihydropyridine antagonist nisoldipine.
      Two components of macroscopic outward current were identified from voltage-step
      and ramp depolarizations. The predominant charge carrier of the net outward
      current was identified as K+ by tail-current experiments (reversal potential, 
      61.0 +/- 0.8 mV in 10.8 mM [K+]o 0 mM [K+]i). The first component was a small,
      low-noise, voltage- and time-dependent current that activated between -40 and -30
      mV (IK(dr)), and the second component was a larger, noisier, voltage- and time
      dependent current that activated at potentials positive to +10 mV (IK(Ca)). Both
      IK(dr) and IK(Ca) displayed little inactivation during long (4-second) voltage
      steps. IK(Ca) and IK(dr) could be pharmacologically separated by using various
      Ca2+ and K+ channel blockers. IK(Ca) was substantially inhibited by external
      NiCl2 (500 microM), CdCl2 (300 microM), EGTA (5 mM), tetraethylammonium (Ki at
      +60 mV, 307 microM), and charybdotoxin (100 nM) but was insensitive to 4
      aminopyridine (0.1-10 mM). IK(dr) was inhibited by 4-aminopyridine (Ki at +10 mV,
      723 microM) and tetraethylammonium (Ki at +10 mV, 908 microM) but was insensitive
      to external NiCl2 (500 microM), CdCl2 (300 microM), EGTA (5 mM), and
      charybdotoxin (100 nM). Two types of single K+ channels were identified in cell
      attached patches. The most abundant K+ channel that was recorded exhibited
      voltage-dependent activation, was blocked by external tetraethylammonium (250
      microM), and had a large single-channel conductance (232 +/- 12 pS with 150 mM K+
      in the patch pipette, 130 +/- 17 pS with 5.4 mM K+ in the patch pipette). The
      second channel was also voltage dependent, was blocked by 4-aminopyridine (5 mM),
      and exhibited a smaller single-channel conductance (104 +/- 8 pS with 150 mM K+
      in the patch pipette, 57 +/- 6 pS with 5.4 mM K+ in the patch pipette). These
      results suggest that depolarization of canine renal artery cells opens
      dihydropyridine-sensitive Ca2+ channels and at least two K+ channels.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1381294
TI  - Decreased collagen gene expression and absence of fibrosis in thyroid hormone
      induced myocardial hypertrophy. Response of cardiac fibroblasts to thyroid
      hormone in vitro.
AB  - The regulatory effects of thyroid hormone on biosynthesis of myocardial proteins
      that originate from cardiac myocytes are well established. Little is known,
      however, of regulatory effects of thyroid hormone on interstitial proteins. In
      this study we examined the effects of thyroid hormone on collagen gene expression
      in thyroid hormone-induced myocardial hypertrophy and the response of cardiac
      fibroblasts to thyroid hormone in culture. Adult male Sprague-Dawley rats were
      treated intraperitoneally with L-thyroxin (10 micrograms/100 g body wt) for 2
      hours or 1, 2, 3, 6, 12, or 14 days. Northern blot analysis of RNA from total
      ventricular tissue showed that after 2 hours of treatment, the abundance of mRNA
      for pro alpha 2(I) collagen decreased by 53% (p less than 0.05) and reached the
      lowest level (60% decrease, p less than 0.02) at day 1, remained diminished at
      day 3, and then gradually returned toward normal levels. After transient
      transfection of chimeric DNA containing collagen type I promoter-chloramphenicol
      acetyl transferase (CAT) gene into the thyroxin-treated cardiac fibroblasts, the
      level of CAT activity decreased significantly. Treatment of cardiac fibroblasts
      in culture (10 nM L-thyroxin) resulted in a 33% (p less than 0.005) decrease in
      the abundance of mRNA for pro alpha 2(I) collagen. The stability of the mRNA for
      pro alpha 2(I) collagen in cardiac fibroblasts, as measured by mRNA half-life,
      was slightly (16.6%) decreased by thyroid-hormone treatment. Collagen synthesis
      as shown by immunofluorescent staining of intracellular collagen in cultured
      fibroblasts and in frozen sections of myocardium was also diminished.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1381295
TI  - Epicardial excitation during ventricular pacing. Relative independence of
      breakthrough sites from excitation sequence in canine right ventricle.
AB  - In a previous investigation, epicardial recordings with 1,124 closely spaced
      electrodes revealed 20-35 breakthrough (BKT) sites and an equal number of
      separate wave fronts on the ventricular surface of exposed dog hearts during
      normal sinus rhythm. In the present study we tried 1) to determine whether
      ventricular pacing also produced multiple BKTs and wave fronts and 2) to
      determine whether the number and location of BKTs were, to some degree,
      independent of pacing site. The study mainly focused on right ventricular BKTs
      observed during right ventricular pacing. To test hypotheses 1 and 2 we
      identified many breakthrough sites during sinus rhythm in seven exposed dog
      hearts and then paced the heart from several BKT and non-BKT sites on the right
      ventricle. Epicardial potential maps and excitation time maps were obtained by
      using 1,124 epicardial electrodes covering the anterior right ventricle and part
      of the anterior left ventricle. A primary wave front spread radially for several
      centimeters from the pacing site, and no BKTs appeared in the areas covered by
      the primary wave front. In the remaining areas (secondary areas), multiple BKTs
      appeared; their number was close to that observed during sinus rhythm in the same
      areas (113 versus 115, respectively, in 12 paced beats). The majority of paced
      BKTs (83 out of 115, or 72%) occurred exactly at the same locations where they
      appeared during sinus rhythm. However, 30 right ventricular BKTs observed during
      sinus rhythm disappeared in the secondary areas and were replaced by
      approximately the same number of new BKTs. Many areas without BKTs in normal
      beats remained so in paced beats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381296
TI  - Electrophysiological effects of myocardial stretch and mechanical determinants of
      stretch-activated arrhythmias.
AB  - BACKGROUND: Although the existence of myocardial mechanoelectrical feedback is
      well established, the mechanism of arrhythmia induction by ventricular dilatation
      or stretch remains insufficiently defined. In particular, controversy exists when
      comparing the arrhythmogenic potential of chronic versus acute myocardial
      stretch. Also, assessment of cellular electrophysiological effects of myocardial
      stretch has been incomplete. METHODS AND RESULTS: To evaluate the
      electrophysiological and arrhythmogenic effects of slow versus rapid ventricular
      wall stretch, we developed an isolated Langendorff-perfused rabbit heart model in
      which left ventricular (LV) volume can be changed by a computer-controlled
      servopump. Cellular electrophysiological effects and premature ventricular
      excitations (PVEs) and their origin produced by the volume increases were
      assessed by a multiple-site monophasic action potential (MAP) recording system
      and by volume-conducted ECGs obtained by immersing the entire preparation in a
      saline-filled tank. Volume was increased either gradually with slow volume ramps
      (0.1 ml/sec) or suddenly by volume pulses of varying pulse waveforms (three
      different amplitudes and five different rise velocities) applied randomly 250-350
      times to each of eight hearts. Gradual LV volume loading caused gradual decreases
      in MAP resting and action potential amplitude, whereas rapid, transient volume
      pulses caused transient depolarizations. Despite similar membrane potential
      effects of stretch, gradual volume increases rarely (11%) produced PVEs, even
      with large volume loads, whereas rapid volume pulses of moderate amplitudes
      regularly triggered PVEs (45-100% of interventions). Logistic regression analysis
      showed that the probability of PVE occurrence increased independently with both
      the amplitude and the velocity of the volume increase, with the greatest
      sensitivity to stretch velocity exhibited at low and intermediate pulse
      amplitudes. Faster volume pulse rise velocities triggered PVEs at a lower
      instantaneous pulse amplitude than lower rise velocities, further corroborating
      the dependence of stretch-activated arrhythmias on the velocity of stretch. In
      contrast, an increase in the basic ventricular volume had no effect on the
      probability of PVE occurrence during the volume pulses. The MAP recordings
      demonstrated spatial variability in the extent of local depolarizations and site
      of PVE origin; transient depolarizations occurred, and PVEs originated most often
      in the posterolateral region of the left ventricle. CONCLUSIONS: Membrane
      depolarization is caused by both gradual and rapid ventricular stretch, but PVEs
      are more easily elicited by rapid stretch. Regions of greater myocardial
      compliance that experience greater relative stretch may act as "foci" for stretch
      activated arrhythmias during dynamic ventricular loading. These whole-heart data
      corroborate the existence of stretch-activated membrane channels in ventricular
      myocardium and may help explain ventricular ectopy under conditions of
      differential ventricular loading, as in ventricular dyskinesia, or regional
      muscle traction, as in mitral valve prolapse syndrome.

PMID- 1381297
TI  - Protective effects of cyclophosphamide, cyclosporin A and FK506 against antigen
      induced lung eosinophilia in guinea-pigs.
AB  - A close association has been recognized between activated T cells and eosinophils
      in asthma, albeit circumstantial. The present study attempted to investigate this
      relationship in an animal model of lung eosinophilia using the new generation of
      T cell-selective immunosuppressants, cyclosporin A and FK506, compared with the
      myelotoxic immunosuppressive agent cyclophosphamide. Antigen challenge of
      ovalbumin-sensitized guinea-pigs resulted in a lung eosinophilia which was
      assessed by bronchoalveolar lavage. All three agents caused a marked suppression
      of lung eosinophilia at 24 h post-challenge when the compounds were administered
      at the time of sensitization but not when administered for 3 days before lavage.
      However, the lung eosinophilia at 72 h post-challenge was reduced significantly
      by FK506 and by cyclophosphamide, but not by cyclosporin A, when the drugs were
      administered for 3 days, before lavage. These results strongly suggest the
      involvement of T cells in antigen-induced late phase (72 h) eosinophilia in
      guinea-pigs but not at 24 h. The effects of cyclophosphamide were always
      associated with a reduction in circulating white cell counts, whereas cyclosporin
      A and FK506 showed no myelotoxic properties. These results suggest the potential
      therapeutic use of selective, non-cytotoxic immunosuppressive agents in asthma.

PMID- 1381298
TI  - Increased LAK activity against HIV-infected cell lines in HIV-1+ individuals.
AB  - The role of natural killer (NK) cells and their inducible counterparts,
      lymphokine-activated killer (LAK) cells in AIDS with regard to HIV-1 viral
      immunosurveillance and the control of secondary opportunistic disease has yet to
      be established. In this study, we have demonstrated that LAK cells derived from
      all HIV-1+ groups showed striking increases in their capacity to lyse HIV-1
      infected U-937 cells relative to their uninfected U-937 counterparts.
      Surprisingly, similarly derived LAK cells from healthy seronegative controls
      showed no differences in their lysis of HIV-1-infected versus uninfected U-937
      cells. The differential ability of LAK effectors from seropositive donors to lyse
      HIV-1-infected targets was demonstrable using a number of U-937 subclones and
      their HIV-1-infected counterparts. Again, no differences in LAK cell-mediated
      lysis of HIV-1-infected and uninfected U-937 subclones were observed in
      seronegative individuals. Our findings that HIV-1+ individuals show selective
      expansion of non-MHC restricted, HIV-1-directed cytotoxic LAK cells indicate that
      natural immunity may indeed play a role in HIV-1 viral immunosurveillance.

PMID- 1381299
TI  - Characterization of an anti-idiotypic MoAb bearing an internal image of the
      receptor-binding epitope of cholera toxin.
AB  - A mouse anti-cholera toxin (CT) MoAb, mAb1, specific for the GM1-binding epitope
      of CT, was used to raise a syngenic anti-idiotypic MoAb, mAb2. Purified mAb2 was
      specific for mAb1 as shown by latex particle counting immunoassay and ELISA.
      Several experiments of competition between mAb2 and CT for binding to mAb1
      demonstrated that mAb2 bore an internal image of the GM1-binding epitope of CT.
      Binding of mAb2 to GM1 unambiguously corroborated the mAb1-paratopic specificity
      of mAb2. Furthermore, mAb2 acted as a CT-surrogate antigen: rabbits injected with
      mAb2 produced some anti-CT antibodies, Ab3, which resembled mAb1 in specificity
      as expected. The potential use of this mAb2 as vaccine or as prophylactic agent
      to prevent CT from binding to its cellular receptor is discussed.

PMID- 1381300
TI  - Characterization of B cell epitopes on the 16K antigen of Mycobacterium
      tuberculosis.
AB  - To characterize the antigenic parts of the 16K protein of Mycobacterium
      tuberculosis, overlapping peptides according to the amino acid sequence of the
      16K protein were synthesized. In total, 14 peptides of 20 amino acids in length
      with an overlap of 10 amino acids and two additional decapeptides (amino acids 31
      40 and 61-70) were tested with eight anti-16K MoAbs and human sera. The common
      recognition site of MoAbs F67-8 and F67-16 was LRPTFDTRLM (amino acids 31-40) and
      of MoAbs F159-1 and F159-11 DPDKDVDIMV (amino acids 61-70). However, for binding
      of the MoAbs to these peptides additional amino acids were required at either the
      N- or C-terminus, suggesting that some kind of conformation is required. The
      recognition sites of the MoAbs F23-41, F23-49, F24-2 and TB68 could not be
      identified using the peptides, indicating that the MoAbs only bound to
      conformational epitopes and not to peptides which may contain parts of these
      epitopes. The MoAbs bound to beta-galactosidase fusion proteins comprising parts
      of the 16K protein, indicating that some kind of native conformation is present
      on the recombinant proteins. Sera from 14 of 19 patients with tuberculosis and
      none from 19 controls reacted with the purified 16K protein. Sera from four of
      these 14 patients reacted with two overlapping peptides (amino acids 71-100).
      Apparently, antibodies in patients' sera against the 16K protein are
      predominantly directed against conformational epitopes.

PMID- 1381301
TI  - Cells with natural killer activity in human rabies.
AB  - Cytotoxic lymphocyte function in 13 patients with rabies was studied by counting
      the number of CD56 cells and assessing natural killer (NK) cell activity. There
      was no significant difference in the number of killer cells between rabies
      patients and 31 normal controls (P greater than 0.05). Two of six non-fatal
      encephalitic patients due to causes other than rabies had reduced CD56 numbers.
      Base-line NK cell responses versus K562 cell targets did not differ among the
      normal control and rabies groups (P greater than 0.05). Study of the non-rabies
      encephalitis group showed heterogeneous results with wide variation. Significant
      enhancement of NK activity was seen in four rabies patients and in 10 normal
      control subjects tested after interferon-alpha (IFN-alpha) and IL-2. None of the
      four patients with encephalitis due to causes other than rabies showed such
      enhancement. Our results suggest that NK cells of rabies patients are not fully
      stimulated and that this might contribute to the virulence of rabies. The cause
      of this phenomenon remains unknown.

PMID- 1381302
TI  - Hepatitis C: a possible etiology for cryoglobulinaemia type II.
AB  - Out of 15 successive patients with mixed essential cryoglobulinaemia type II
      (monoclonal IgM kappa/IgG), 13 had serological evidence for hepatitis C infection
      as shown by specific enzyme immunoassays and immunoblot. RNA was purified from
      the serum of seven patients and hepatitis C sequences were identified in five
      following reverse transcription and DNA amplification. The liver histology showed
      chronic active hepatitis with or without cirrhosis in the 12 patients with
      hepatitis C who had a liver biopsy. The two patients without serological evidence
      of hepatitis C suffered from haematological malignancies. Hepatitis C may be a
      major etiological agent of cryoglobulinaemia type II.

PMID- 1381303
TI  - Induction of a pharmacologically active clonotypic B cell response directed to an
      immunogenic region of the human beta 2-adrenergic receptor.
AB  - It has been reported that autoantibodies against the beta 2-adrenergic receptors
      are involved in the pathology of allergic disorders and of Chagas' disease.
      Therefore, the immune response against a peptide (H26Q) corresponding to the
      putative second extracellular loop of the human beta 2-adrenergic receptor, which
      could be a target for autoantibody attack, was analysed in view of its possible
      immunogenicity. The free peptide induced a T cell-mediated humoral response in
      the context of three different murine MHC haplotypes. The T cell epitope was
      found to be localized in the N-terminal region of the peptide. Highly specific T
      helper cells were capable of stimulating B cells with the potential to generate a
      large antibody repertoire reactive with the loop peptide. MoAbs were screened to
      analyse this B cell response for antibodies potentially interfering with receptor
      function and a MoAb was found that impaired ligand binding to the receptor.

PMID- 1381304
TI  - Expression of CD56 (NKH-1) differentiation antigen in human thyroid epithelium.
AB  - Leu-19 (CD56) MoAb is well known to recognize gp220 expressed on natural killer
      (NK) cells and is widely used as a NK cell marker. The expression of CD56 antigen
      was tested by means of sensitive alkaline phosphatase-anti-alkaline phosphatase
      (APAAP) immunohistochemical technique and the above mentioned MoAb as a primary
      antibody, on frozen sections of various fresh human tissues. Out of 11 organs
      examined only thyroid gland provided a distinct reaction confined to cell
      membranes of epithelial follicular cells. The reaction had a diffuse pattern in
      cases of Graves' disease and colloidal goitre while in Hashimoto's thyroiditis
      presented as a focal pattern. Other anti-NK cell MoAbs such as VD4 (CD16) and Leu
      7 (CD57) reacted only with single cells of thyroid stroma. The results of APAAP
      staining were confirmed by the cytofluorimetric assessment of isolated thyroid
      cells. It is speculated that CD56 expression on thyroid cells may have a
      functional significance, perhaps related to neural-endocrine interactions.

PMID- 1381305
TI  - The prognostic significance of very low frequency ventricular ectopic activity in
      survivors of acute myocardial infarction. BHAT Study Group.
AB  - Survivors of myocardial infarction with less than 2 PVC/h on 24-h ambulatory
      electrocardiography were followed up for an average of 25 months (11 to 40
      months) while receiving a placebo (1,222 patients) or propranolol, 180 or 240
      mg/day (1,234 patients). Three quarters of the participants with PVCs had an
      average of less than 2 PVC/h. Only 16 percent did not have any ventricular
      ectopic activity during the 24 h. Analysis of total mortality according to the
      number of premature ventricular complexes per hour showed that patients who had
      PVCs with a very low frequency (less than 0.5/h) had 49 percent higher mortality
      than patients who did not have any PVC. Patients who had greater than 0.5 PVC/h
      but less than 1 PVC/h had a statistically significant higher mortality rate, 11.7
      vs 4.1 percent (p less than 0.0001) than patients who had no PVC. These data
      indicate that low ventricular ectopic activity frequency is associated with
      increased mortality in survivors of acute myocardial infarction.

PMID- 1381306
TI  - The thermal transition in crude myelin proteolipid has a lipid rather than
      protein origin.
AB  - Myelin proteolipid has been isolated from bovine brain and purified using organic
      solvents according to conventional procedures. The protein content of the
      purified sample, or crude proteolipid, contains a minimum of 75% w/w of
      proteolipid, with DM-20, a proteolipid molecule with an internal deletion of 35
      out of 276 amino acid residues, as the only other component. Biochemical analysis
      has shown the differences in lipid composition between brain white matter, myelin
      and crude proteolipid preparations. The latter contained practically no
      cholesterol, while the other two samples had about 22-23% w/w. High-sensitivity
      differential scanning calorimetry experiments with both crude proteolipid and its
      extracted pool of lipids have shown similar reversible thermal transitions at 52
      degrees C and 48 degrees C. The effect of increasing amounts of cholesterol on
      the two calorimetric transitions led in both cases to a continuous decrease in
      the melting temperature and in the transition enthalpy. Parallel Fourier
      transform infrared spectroscopy studies of crude proteolipid have detected a
      reversible, co-operative lipid transition centred at 49 degrees C, with no
      detectable change in the amide region between 20 degrees C and 60 degrees C. Once
      more an increase in cholesterol content led to a decrease in the sharpness of
      this transition. It is concluded that the thermal transition detected in crude
      proteolipid, which has in the past been attributed to proteolipid thermal
      denaturation (Mateo et al. 1986), actually corresponds to a thermotropic phase
      transition of the lipids included in the crude proteolipid sample.

PMID- 1381307
TI  - The inhibition of rat adrenal cytochrome P-45011 beta gene expression by
      androgens.
AB  - The synthetic androgen methylandrostenediol (MAD) and the naturally occurring
      one, testosterone, both bring about hypertensive cardiovascular disease when
      chronically administered to rats. The pathogenesis of this form of experimental
      hypertension is thought to result from inhibition of steroid 11 beta-hydroxylase
      activity. In contrast to the above androgens, 19-nortestosterone, androstenedione
      and dehydroepiandrosterone (DHEA) have been reported to be without effect in
      elevating blood pressure. To examine the mechanism(s) involved, we have in this
      study compared the effects of a number of androgens on adrenal cytochrome P-
      45011 beta enzyme and mRNA steady state levels. These parameters were also
      correlated with the ability of adrenal mitochondria isolated from these groups to
      hydroxylate 11-deoxycorticosterone (DOC) to corticosterone and 18-hydroxy-11
      deoxycorticosterone (18-hydroxy-DOC). Rats treated for seven days with 10 mg per
      day of dihydrotestosterone, testosterone, 19-nortestosterone or MAD showed a
      profound decrease in cytochrome P-45011 beta mRNA levels (to less than 20% of
      controls). This was accompanied by similar changes in both the level and activity
      of the enzyme. Androstenedione and DHEA were less potent in effecting these
      changes. In addition, for MAD and testosterone we tested the dose dependence of
      these changes and found that increasing doses (0.1 mg to 10 mg per day) of either
      androgen caused progressive decreases in the parameters measured. To assess
      selectivity we also determined the steady state level of cytochrome P-450scc mRNA
      in rats treated with the various androgens. In contrast to what was found with
      cytochrome P-45011 beta, the mRNA transcript for cytochrome P-450scc was equal to
      or above control levels. We conclude that, in general, the extent of inhibition
      of cytochrome P-45011 beta enzyme and mRNA level by a given androgen correlates
      with its reported facility in producing hypertension in rats. Increased secretion
      of DOC continues to be a likely mechanism for the development of this
      hypertension but with some androgens extra-adrenal effects may be involved.

PMID- 1381308
TI  - Altered patterns of T cell migration through lymph nodes and skin following
      antigen challenge.
AB  - Antigen challenge has profound effects on a regional lymph node (LN); it leads to
      an increase in blood flow to the node, and a marked increase in lymphocyte output
      through the efferent lymphatics. We used the isolated LN model developed in the
      sheep to see if antigen challenge in a LN resembled inflammation in peripheral
      tissues. Following stimulation with an antigen (purified protein derivative of
      tuberculin), lymphocyte output from the LN showed the typical periods of
      "lymphocyte shutdown" and "recruitment". The shutdown phase, when cell numbers in
      efferent lymph dropped by approximately 80%, affected almost exclusively the
      naive-type (adhesionlo, L-selectin+) T cell population. The large increase in T
      cell traffic through the node during the recruitment phase was mostly due to CD4+
      memory-type T cells and, moreover, the majority of these T cells were L-selectin
      , indicating that these cells were crossing from the blood by a molecular
      mechanism other than L-selectin interaction with its ligand, the "lymph node
      vascular addressin" (MECA-79). Examination of LN high endothelial venules
      revealed the presence of vascular cell adhesion molecule-1 (VCAM-1), an
      endothelial adhesion molecule which has been reported to bind preferentially
      memory-type T cells in inflammatory lesions. Within the skin, antigen challenge
      also induced the rapid expression of VCAM-1 on vascular endothelium. It was
      purely memory-type T cells (beta 1+, L-selectin+/-) that collected in lymph
      draining from this tissue. However within chronically inflamed skin, the MECA-79
      determinant appeared on vascular endothelium, and a small proportion of T cells
      draining from chronically inflamed skin were of naive-type. The present results
      illustrate that there are similarities in the cellular and molecular events that
      characterize antigen stimulation of a LN and inflammation in a peripheral tissue.

PMID- 1381309
TI  - Cytotoxic T lymphocyte responses in the peripheral blood of children born to
      human immunodeficiency virus-1-infected mothers.
AB  - Cytotoxic T lymphocytes (CTL) are present at high activities in adult patients
      infected with the human immunodeficiency virus (HIV). In this report, CTL
      effectors were identified in peripheral blood mononuclear cells (PBMC) of
      children born to HIV-1-infected mothers. These CTL killed HLA-matched HIV-1
      infected H9 target cells or doubly transfected P815-A2-env, gag or nef mouse
      tumor cells, which expressed the viral antigens in association with HLA-A1/A3 or
      HLA-A2, respectively. HIV-1-specific CTL were detected early after birth (less
      than 2 months) and remained present during the asymptomatic phase of the
      infection. As in HIV-1-infected adults, HIV-specific CTL declined with disease
      progression. Surprisingly, HIV-1-specific CTL were detected in the PBMC of three
      children who subsequently became seronegative.

PMID- 1381310
TI  - Production of 17.2.25 mu transgenic and endogenous immunoglobulin in X-linked
      immune deficient mice.
AB  - In M54 mice transgenic for a completely rearranged mu(a) heavy chain there is a
      decrease in total B cells and the rearrangement of endogenous immunoglobulin
      genes is partially inhibited. Surprisingly, however, endogenous immunoglobulin
      gene rearrangement and significant heavy chain polypeptide production does occur.
      We tested the hypothesis that only CD5+ B cells produce endogenous immunoglobulin
      by taking advantage of the fact that X-linked immune deficient (xid) mice
      normally are deficient in CD5+ B cells. We found that the frequency of CD5+
      splenic B cells was similar in XxidY transgenic and non-transgenic F1 males, and
      in XxidX transgenic and non-transgenic F1 females. In both XxidX and XxidY
      transgenic F1 mice some, but not all, splenic B cells are CD11b+. There was a
      striking deficit of splenic B cells expressing endogenous immunoglobulin in XxidY
      transgenic mice, although this was not true for peritoneal cells. Thus, the
      introduction of the 17.2.25 mu transgene does not prevent the development of CD5-
      B cells nor does it limit endogenous immunoglobulin gene arrangement and
      expression solely to CD5+ B cells. However, in mice capable of expressing B cell
      surface CD5 or CD11 this transgene can lead to expansion of the fraction of B
      cells positive for these molecules. We conclude that while the introduction of
      the 17.2.25 mu transgene alters the frequencies of B cell populations, maturation
      is not limited to one subpopulation.

PMID- 1381311
TI  - The adjuvant effect of Vibrio cholerae and Escherichia coli heat-labile
      enterotoxins is linked to their ADP-ribosyltransferase activity.
AB  - This study addressed the question of whether the mucosal adjuvant property of
      cholera toxin (CT) and the structurally closely related Escherichia coli heat
      labile toxin (LT) requires the enterotoxic and adenylate cyclase/cAMP activating
      property of these molecules. Therefore, we investigated the cytotoxic and
      adjuvant abilities of the enterotoxins and compared the results with those
      obtained with the non-toxic CT and LT derivatives; recombinant CTB (rCTB) and a
      mutated LT (mLT), which had a single amino acid substitution in position 112 (Glu
      ---Lys) of the A subunit. Detailed functional studies revealed that, in contrast
      to the enterotoxins, both rCTB and mLT lacked ADP-ribosylating and cAMP
      stimulating abilities. However, similar membrane ganglioside GM1-receptor binding
      ability of all the putative adjuvants was demonstrated. When the probe antigen,
      keyhole limpet hemocyanin (KLH), was given perorally together with CT or LT
      strong gut mucosal anti-KLH immune responses were stimulated, whereas no or very
      low anti-KLH responses were seen in the groups which received antigen admixed
      with rCTB or the mLT. Moreover, the specific serum antibody responses to the
      various immunization protocols closely paralleled the local anti-KLH response in
      the gut. From these results it appears that the adjuvant mechanism of LT, and
      probably also of CT, is linked to the ability to ADP-ribosylate and to stimulate
      cAMP formation. However, this study does not unequivocally rule out other
      possibilities such as interactions by the A1 fragment of CT or LT with other G
      proteins than Gs alpha or events that parallel or precede the effects on the
      adenylate cyclase/cAMP system. Thus, the levels of ADP-ribosylation and cAMP
      induction that are required and the key event or target cell that is responsible
      for the adjuvant effect of CT and LT remain to be elucidated. Studies are
      underway to address these issues.

PMID- 1381312
TI  - Mouse tumor rejection antigens P815A and P815B: two epitopes carried by a single
      peptide.
AB  - Mouse mastocytoma P815 expresses several distinct tumor rejection antigens
      recognized by syngeneic cytolytic T lymphocytes (CTL). Two of these tumor
      rejection antigens, P815A and P815B, are encoded by gene P1A, the sequence of
      which was reported previously. Tumor cell variants having lost one or both of
      these antigens were isolated by in vitro selection with CTL and also by
      collecting tumor cells that progressed in vivo after escaping a nearly complete
      immune rejection process. The structure of gene P1A in these antigen-loss
      variants was examined. Several A-B- variants presented a complete or partial
      deletion of the gene. One variant that had lost only antigen A displayed a point
      mutation in the first exon. Peptides were synthesized that corresponded to the
      normal sequence located in the region of this point mutation. They sensitized
      target cells to both anti-A and anti-B CTL. The homologous peptide encoded by the
      mutated gene of the P815 A-B+ variant sensitized cells only to anti-B CTL. We
      conclude that anti-A and anti-B CTL recognize on the same peptide two distinct
      epitopes that are affected differently by the mutation.

PMID- 1381313
TI  - Discrimination of human CD4 T cell clones based on their reactivity with antigen
      presenting T cells.
AB  - In this report, we describe the discrimination of human T cell clones based on
      their reactivity with activated T cells as antigen-presenting cells (APC). CD4+ T
      cell clones specific for peptide P30 of tetanus toxin (amino acids 947-967) and
      restricted to the DP4 molecule were established and tested for proliferation to
      peptide presented either by peripheral blood mononuclear cells (PBMC), Epstein
      Barr virus (EBV)-transformed B cells or major histocompatibility complex (MHC)
      class II-expressing T cells. We found two sets of T cell clones: one set
      proliferated to peptide presentation by PBMC, EBV-transformed B cell lines (EBV-B
      cells) and MHC class II+ T cells (termed T-responder clones), while the other set
      of clones was only stimulated to proliferate, if the peptide was presented by
      PBMC or EBV-B cells, but not by T cells (T-nonresponder clones). Nevertheless,
      these T-nonresponder clones recognized P30 also on T cells, as revealed by Ca2+
      influx. The discrimination of the clones was not due to different avidities of
      the T cell receptors (TcR) of individual clones for the MHC-peptide complex as T
      responder and T-nonresponder clones had similar dose-response curves to P30
      presented by fixed EBV-B cell lines. Addition of cytokines [interleukin (IL)-1,
      IL-2, IL-4 and interferon gamma] did not change the proliferative response of the
      clones, which was consistent throughout an observation period of greater than 4
      months. T-nonresponder clones, exposed to P30 on MHC class II-expressing T cells,
      became not anergic, as they could be restimulated by P30 presented on EBV-B
      cells. The measurement of a panel of T cell activation markers and adhesion
      molecules on T-responder and T-nonresponder clones revealed a higher expression
      of the CD28 molecule on the T-nonresponder clones. The data suggest that freshly
      cloned T cells can be differentiated by peptide presentation on classical (PBMC,
      EBV-B cells) or non-classical APC (class II+ T cells), and that this
      discrimination is further underlined by different levels of adhesion molecules.

PMID- 1381315
TI  - Protective effect of anti-interleukin (IL)-6 antibody against endotoxin,
      associated with paradoxically increased IL-6 levels.
AB  - Two rat monoclonal antibodies (6B4 and 20F3) against mouse interleukin (IL)-6
      were studied for their effects on the generalized Shwartzman reaction and on
      cytokine production elicited by endotoxin injections. Both antibodies were found
      to protect mice against the generalized Shwartzman reaction. Production of
      interferon and tumor necrosis factor in these animals, as assessed from serum
      levels, were not consistently affected by the antibody treatment, although rather
      increased levels were occasionally noted. Paradoxically, however, endotoxin
      induced serum levels of IL-6 in anti-IL-6-treated mice were consistently found to
      be markedly increased and also to persist for longer time periods. The more
      vigorous and persistent response may have been due to slower elimination,
      increased synthesis, or a combination of both. Endogenous production of IL-6 in
      mice may be sufficiently large to supersede the neutralizing potential of an
      excess of antibody, as was evident from the fact that ascites fluid of the anti
      IL-6-producing 6B4 hybridoma was biologically active in the IL-6 assay.

PMID- 1381314
TI  - Enhancers of nonspecific immunity induce nitric oxide synthase: induction does
      not correlate with toxicity or adjuvancy.
AB  - A range of bacterial products and related synthetic compounds, either alone or in
      combination, enhance nonspecific resistance to infection and tumors. These
      compounds, which vary in their other properties such as pyrogenicity, toxicity
      and adjuvancy, were used to assess the hypothesis that nonspecific resistance is
      mediated by induction of the L-arginine: nitric oxide (NO) pathway. The results
      obtained show that agents which stimulate nonspecific immunity, such as
      endotoxin, muramyl dipeptide (MDP) and combinations of monophosphoryl lipid A
      (MPL) with either trehalose dimycolate (TDM) or MDP cause a substantial induction
      of Ca(2+)-independent NO synthase in murine lung. In contrast, agents which do
      not stimulate nonspecific resistance, such as either MPL or TDM alone or threonyl
      MDP (ThrMDP), do not induce NO synthase. This difference in the ability of MDP
      and ThrMDP to induce NO synthase in the lung in vivo was also manifest in
      peritoneal macrophages in vivo as well as being evident in the greater than 100
      fold greater potency of MDP in inducing the enzyme in vitro in lung slices. In
      contrast to the good correlation between induction of NO synthase and induction
      of nonspecific resistance, no correlation was observed with either the toxic
      effects of these agents or their adjuvancy.

PMID- 1381316
TI  - Netwhat?
AB  - The hallmark of an antibody response is considered to be its specificity for the
      immunogen. Nonetheless, most antibody elicited by an immunogen has been reported
      to be unreactive with it. We have evaluated specificity by characterizing the
      primary antibody response of mice to heat-aggregated human gamma-globulin with
      four approaches: (a) quantification of antibody-producing cells; (b) hybridoma
      analysis; (c) in situ antigen binding and (d) analysis of secreted antibody. The
      results show that the nonspecific component of this response is negligible. These
      observations suggest that such a component is not a basic feature of the antibody
      response and it is discussed that nonantigen-specific antibody may arise from a
      variety of causes many of which are artifactual.

PMID- 1381317
TI  - Actions of novel bombesin receptor antagonists on pancreatic secretion in rats.
AB  - Recently synthesized highly specific and potent bombesin receptor antagonists
      permit study of the role of endogenous bombesin-like peptides in the
      physiological regulation of pancreatic secretion. We now tested the action of
      three novel pseudononapeptide bombesin/gastrin releasing peptide (GRP)
      antagonists (RC-3095, RC-3100 and RC-3120) on amylase release in vitro from
      isolated rat pancreatic acini and on protein secretion in vivo in chronic
      pancreatic fistula rats. In isolated pancreatic acini, all three bombesin
      receptor antagonists inhibited the amylase secretion induced by bombesin by
      shifting to the right the amylase response to bombesin without altering the
      maximal response. These antagonists alos reduced concentration dependently the
      near-maximal amylase response to bombesin, the concentration required for 50%
      reduction (IC50) being about 10(-7) M for RC-3095 and RC-3100 and 10(-6) M for RC
      3120. None of the bombesin/GRP antagonists used affected the amylase response to
      CCK, pentagastrin or urecholine. In conscious rats with a chronic pancreatic
      fistula, all three bombesin antagonists shifted to the right the pancreatic
      protein response to graded doses of bombesin without changing the maximal
      response. These antagonists inhibited the protein response to constant background
      stimulation with bombesin in a dose-dependent manner, the ID50 being about 20
      nmol/kg per h for RC-3095 and RC-3100 and about 160 nmol/kg per h for RC-3120.
      None of the antagonists significantly affected basal pancreatic secretion or
      secretion induced by sham-feeding, ordinary feeding or the diversion of
      pancreatic juice from the duodenum. These results indicate that exogenous
      bombesin is a potent direct stimulant of pancreatic enzyme secretion.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1381318
TI  - Effect of maturation on histamine-induced airflow obstruction and airway
      microvascular leakage in guinea pig airways.
AB  - To study the effect of maturation on histamine-induced airflow obstruction and
      airway microvascular leakage, we measured concomitant changes in lung resistance
      (RL) and in extravasation of Evans Blue dye in the airways of anesthetized
      immature (aged 14 +/- 2 days) and adult guinea pigs (aged 60 +/- 12 days). RL was
      measured for 6 min after iv. histamine (0, 5, 15, 30 and 50 micrograms/kg). For
      comparison, responses after 1 microgram/kg substance P were also examined. After
      measurement of RL, microvascular leakage in trachea, main bronchi, and proximal
      and distal intrapulmonary airways was also examined in the same animal. Immature
      animals required a larger dose of histamine than adults to achieve a similar
      degree of maximal bronchoconstriction after histamine. In contrast, equal doses
      of histamine (15 and 30 micrograms/kg) induced a significantly greater
      extravasation of dye in immature airways in both proximal and distal
      intrapulmonary airways, although not in trachea or main bronchi. Substance P did
      not cause any age-related differences in dye extravasation at any airway level.
      These results suggest that i.v. histamine specifically causes a greater degree of
      airway microvascular leakage in peripheral airways but induces less smooth muscle
      contraction in the airways of immature guinea pigs than in the airways of adult
      animals.

PMID- 1381319
TI  - Activity of peptide and non-peptide antagonists at peripheral NK1 receptors.
AB  - We investigated the affinity of several tachykinin antagonists reportedly
      selective for NK1 receptors at various tachykinin receptors and NK2 receptors
      subtypes. The four antagonists tested were: L 668,169, Spantide II, Ac-Thr
      DTrp(for)-Phe-NMeBzl (FR 113680) and the novel nonpeptide antagonist (+/-)-CP
      96,345. The four antagonists were found to be effective against NK1 receptor
      mediated responses in the guinea-pig ileum with the following rank order of
      potency (pKB values in parentheses): (+/-)-CP-96,345 (8.11) greater than Spantide
      II (7.08) greater than FR 113680 (6.61) greater than or equal to L 558,169
      (6.44). (+/-)-CP-96,345, Spantide II and FR 113680 were distinctly more potent at
      NK1 receptors than at NK2 receptors (NK2A in the rabbit pulmonary artery, NK2B in
      the hamster trachea). L 668,169 antagonized neurokinin A-induced contractions in
      the hamster trachea with an affinity similar (pKB value 6.16) to that found in
      the guinea-pig ileum for NK1 receptors (pKB value 6.44). All antagonists were
      inactive at NK3 receptors of the rat portal vein. In a second series of
      experiments, the affinities of test antagonists for NK1 receptors in the guinea
      pig ileum were compared to those for NK1 receptors in the guinea-pig vas
      deferens, the rabbit jugular vein and the rat urinary bladder. For each
      antagonist, the affinity measured in the guinea-pig vas deferens and the rabbit
      jugular vein was comparable to that found in the guinea-pig ileum. In the rat
      urinary bladder, (+/-)-CP-96,345 was about 100 times less potent in blocking NK1
      receptor-mediated contractions than in the guinea-pig ileum.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1381320
TI  - Characterization of Chilean, Bolivian, and Argentinian Trypanosoma cruzi
      populations by restriction endonuclease and isoenzyme analysis.
AB  - Ninety-one Chilean, 15 Bolivian, and 9 Argentinian Trypanosoma cruzi stocks,
      isolated from various hosts and vectors, were characterized by schizodeme
      analysis with EcoRI and MspI endonucleases. The three major similar pattern
      groups that emerged from this sample correlated with results of isoenzyme
      analysis. This result confirms previous work and supports the hypothesis of the
      clonal structure of natural populations of T. cruzi, fully defined at the level
      of isoenzyme analysis, quantitative kinetoplast DNA restriction fragment length
      polymorphism, and kinetoplast DNA hybridization analysis. In Chile, sylvatic and
      domestic cycles of T. cruzi transmission appear to be mainly independent:
      genetically different families of natural clones are specific to these cycles.
      Nevertheless, the possibility of overlap remains unclear. Results described here
      indicate that natural clones inhabiting Chilean regions appear genetically
      related to the natural clones identified in neighboring countries. In Chile the
      more frequently sampled parasite types are natural clone 39 and a genetically
      closely related clone NP13. In this work an evaluation of T. cruzi natural clone
      mixtures in T. cruzi stocks from Chile was performed for the first time by
      schizodeme analysis before and after serial transfer in mouse maintenance. The
      results indicate that six of nine stocks are composed of two or more natural
      clones. This observation raises the relevant question of whether specific T.
      cruzi natural clones generate different clinical features of Chagas' disease.

PMID- 1381321
TI  - Brain factor from Galleria mellonella (Lepidoptera) stimulating silk gland
      activity.
AB  - Brain extracts from day 1-4 last instar larvae of Galleria mellonella
      (Lepidoptera) stimulate RNA synthesis in cultured silk glands from day 3 last
      instar larvae. When the fibroin-synthesizing posterior parts of silk glands were
      incubated for 3 h in vitro in the presence of brain extract (0.1 brain
      equivalent), [3H]-uridine incorporation into RNA was stimulated more than
      twofold. The stimulating effect of brain extract showed a dose response
      relationship. It is suggested that the heat-resistant and protease-sensitive
      brain factor is a peptide.

PMID- 1381322
TI  - A marine algal Na(+)-activated ATPase possesses an immunologically identical
      epitope to Na+,K(+)-ATPase.
AB  - Immunological homology was investigated between Heterosigma akashiwo (a marine
      algae) Na(+)-activated ATPase and animal Na+,K(+)-ATPase. The former polypeptide
      [(1989) Plant Cell Physiol. 30, 923-928] reacted with anti-serum raised against
      the amino-terminal half of the pig kidney Na+,K(+)-ATPase alpha subunit. It is
      suggested that the Na+,K(+)-ATPase epitope within the amino-terminal region is
      conserved in the plant Na(+)-activated ATPase, and the region containing the
      epitope may be important for Na ion transport.

PMID- 1381323
TI  - Endothelial nitric oxide synthase is myristylated.
AB  - The enzyme responsible for the synthesis of endothelium-derived relaxing factor
      and/or nitric oxide in the endothelium has been described as a particulate
      enzyme, whereas other isoforms of nitric oxide synthase are soluble enzymes. Here
      we are reporting that endothelial cells metabolically incorporate myristate
      (C14), but not palmitate (C16), into nitric oxide synthase. We are postulating
      that the endothelial-derived nitric oxide synthase is a particulate enzyme
      because of the fatty acid acylation of the protein which 'anchors' the enzyme
      into the membrane either directly or via another membrane-bound protein.

PMID- 1381324
TI  - [Structure-function studies of galanin].
AB  - Galanin is widely distributed in the central and peripheral nervous system and
      exerts a variety of physiological effects. This review briefly describes the
      chemical structure, tissue distribution, physiological effects, receptors and
      structure-function relationships of galanin. It is worth noting that the
      inhibitory effect of newly synthesized galanin (1-15)-ol on guinea pig ileum
      contractions was of the same magnitude as that of galanin. This observation gives
      us an important clue as to the discovery of antagonists of galanin for neural
      systems.

PMID- 1381325
TI  - Analysis of DNA encoding 23S rRNA and 16S-23S rRNA intergenic spacer regions from
      Plesiomonas shigelloides.
AB  - Amplification of the gene encoding 23S rRNA of Plesiomonas shigelloides by
      polymerase chain reaction (PCR), with primers complementary to conserved regions
      of 16S and the 3' end of 23S rRNA genes, resulted in a DNA fragment of
      approximately 3 kb. This fragment was cloned in Escherichia coli and its
      nucleotide sequence determined. The region encoding 23S rRNA shows high homology
      with the published sequences of 23S rRNA from other members of the gamma division
      of Proteobacteria. The sequence of the intergenic spacer region, between the 16S
      and 23S rRNA genes, was determined in a further two clones. In one the sequence
      of a single tRNA(Glu) was found which was absent from the other two. This
      variation in sequence suggests that the different clones may be derived from
      different ribosomal RNA operons.

PMID- 1381326
TI  - Ribosomal RNA gene restriction fragment diversity amongst Lior biotypes and
      Penner serotypes of Campylobacter jejuni and Campylobacter coli.
AB  - Diversity based on ribosomal RNA gene-restriction endonuclease digest patterns
      was detected amongst 42 strains of Campylobacter jejuni and 18 strains of C. coli
      including representatives of 53 different Penner serotypes. HaeIII ribopatterns
      were coded for numerical analysis which showed that all except two were different
      including those of several strains of the same serotype (P2 and P20). At the 30%
      similarity level, four groupings were formed in the analysis of which three
      corresponded to C. jejuni, C. coli and C. lari phenotypes respectively. Eight
      strains (13%) were atypical as their phenotypic and ribopattern associations did
      not correspond. Ribopattern fragments of 3.0, 5.0 and 9.3 kb were characteristic
      of the majority of C. jejuni, whereas 1.5, 2.2-, 2.3- and 4.7-kb fragments were
      commonly present in C. coli. These fragments provided novel species-specific
      markers. We conclude that HaeIII ribotyping was as discriminatory as Penner
      serotyping of C. jejuni and C. coli and may even provide a basis for
      distinguishing between strains of the same serotype and for identifying new
      groups within the thermophilic campylobacters.

PMID- 1381327
TI  - Comparison of DNA strand break induction in CHO cells measured by alkaline
      elution and by fluorometric analysis of DNA unwinding (FADU).
AB  - DNA damage in X-irradiated CHO cells was measured by alkaline filter elution and
      compared to fluorometric analysis of DNA unwinding (FADU). The FADU method proved
      to be as sensitive as the alkaline filter elution technique in detecting X-ray
      induced DNA breaks. Strand break induction was also measured after treatment with
      four radical generating chemicals (hydrogen peroxide, bleomycin, mitomycin C and
      methyl viologen) using the FADU technique.

PMID- 1381328
TI  - [Drug modification of post-traumatic edema of the extremities by the proteinase
      inhibitor aprotinin. An animal experiment study].
AB  - Posttraumatic edema remains a serious problem in traumatology. Unrecognized or
      improperly treated, edema poses a threat to the survival of any extremity,
      particularly the hand, where a number of intricate functional structures are at
      stake. This study, as well as other recent clinical and experimental work, show
      that aprotinin, a proteinase inhibitor, is valuable in the treatment of
      posttraumatic edema, provided it is given as early as possible and in an adequate
      dosage.

PMID- 1381329
TI  - [Synthetic grafts for palliative bilioenteric bypass in proximal malignant
      biliary obstruction].
AB  - Hepatico-jejunostomy bypass is technically very demanding when used for proximal
      malignant biliary obstruction. The use of synthetic vascular grafts may simplify
      these operations. Our recent clinical experience and published reports support
      the selective use of synthetic grafts in the operative treatment of malignant
      obstructive jaundice.

PMID- 1381330
TI  - [Drug therapy in severe tumor pain. Comparative study of a new combination
      preparation versus diclofenac-Na].
AB  - In a multicentric, interindividual, double-blind study, the analgesic action,
      duration of effect, tolerability and side effects of the new combination
      preparation, Combaren (diclofenac-Na 50 mg+codeine phosphate 50 mg), were
      compared with those of diclofenac-Na 50 mg (Voltaren 50) in 184 patients with
      severe tumor-related pain. The results show that Combaren is a highly effective
      preparation for the treatment of severe tumor pain. The combination of diclofenac
      Na with codeine phosphate leads to a clear, statistically significant,
      augmentation of the effectiveness of additionally used analgesics on pain
      severity, and the general effectiveness of the combination is more positively
      assessed that that of monotherapy with diclofenac (also effective). In the staged
      approach to the treatment of malignancy-related pain in which the aim is to
      provide continuous, preventive analgesia rather than ad hoc treatment of newly
      developing or worsening pain, this combination preparation will presumably find a
      permanent place in stage I/II of the generally accepted staged pain-treatment
      scheme.

PMID- 1381331
TI  - Thyrotropin and prolactin secretion are not affected by porcine and rat galanin
      in normal subjects.

PMID- 1381332
TI  - Characterization of HeLa cell vacuoles induced by Helicobacter pylori broth
      culture supernatant.
AB  - Helicobacter pylori broth culture supernatants induce eukaryotic cell vacuolation
      in vitro, a phenomenon that has been attributed to cytotoxic activity. We sought
      to characterize further the vacuolation of HeLa cells that occurs in response to
      H pylori culture supernatant. Nascent vacuoles were detectable by electron
      microscopy after 90 minutes of incubation with H pylori supernatant and were not
      associated with any identifiable organelle. After 6 days of incubation with H
      pylori supernatant, vacuoles were membrane-bound structures filled with electron
      dense debris, which resembled secondary lysosomes. Acid phosphatase activity was
      detected within the vacuoles. The vacuoles induced by H pylori supernatant were
      then compared with vacuoles induced by trimethylamine, a weak base known to
      induce lysosomal swelling. Neutral red dye rapidly entered the vacuoles induced
      by either H pylori supernatant or trimethylamine, and both types of vacuoles were
      reversible. Compared with trimethylamine-induced vacuoles, the vacuoles induced
      by H pylori supernatant were larger and typically lacked a limiting membrane. In
      the early stages of formation, vacuoles induced by trimethylamine were labeled by
      lucifer yellow, a pinocytotic marker, whereas H pylori cytotoxin-induced vacuoles
      were not. These data suggest that trimethylamine-induced vacuoles arise directly
      from endocytic compartments, whereas H pylori cytotoxin induces vacuole formation
      via an autophagic mechanism.

PMID- 1381333
TI  - Analysis of epithelial and lymphoid phenotypic markers in relation to growth
      pattern of colorectal adenomas.
AB  - The relationship of villous to tubular adenomas is poorly understood and often
      difficult to characterize morphologically. A villous growth pattern in colorectal
      adenomas has been associated with a higher frequency of high-grade dysplasia. We
      compared phenotypic markers using immunoperoxidase techniques in paired samples
      of villous (75% to 100% villous) and pure tubular adenomas matched for size and
      degree of dysplasia, which were selected by review of 1,000 polyps from our
      files. The following monoclonal antibodies were used: CAM 5.2 and AE1/AE3 to
      cytokeratins; B18, D14, B7.1, and B7.8 to four distinct carcinoembryonic antigen
      epitopes; Leu-M1 and LN3 to HLA-DR antigen; LN2 to invariant chain class II major
      histocompatibility complex; LN1 and MB2 to B-cell markers; UCHL1 and MT1 to T
      cell markers; Leu-7 to natural killer cells; Mac 387 to macrophages; S-100 to
      Langerhans-type cells; and a polyclonal antibody to secretory component. LN3
      reactivity correlated with villous morphology and secretory component correlated
      with tubular morphology. Combined HLA-DR and secretory component expression
      discriminated between tubular and villous growth patterns in 12 of 15 pairs of
      adenomas (P less than .001). LN2 was expressed more frequently than LN3, but did
      not correlate with growth pattern. Neuroendocrine cells (Leu-7) were more
      frequent in tubular adenomas. Carcinoembryonic antigen epitopes did not relate to
      growth pattern. We did not confirm previously reported differences in cytokeratin
      expression. We concluded that among the markers tested, HLA-DR expression, which
      may have an immunologic basis, is most characteristic of colorectal adenomas that
      exhibit a villous growth pattern.

PMID- 1381334
TI  - Monocytoid B-cell lymphomas: an assessment of diagnostic criteria and a
      perspective on histogenesis.
AB  - To determine which morphologic criteria are most useful in distinguishing
      reactive from malignant monocytoid B cells (MBCs), we compared 16 monoclonal
      cases (11 nodal, five extranodal) of monocytoid B-cell lymphoma (MBCL) with 12
      cases of various reactive diseases in which MBCs were polyclonal. The results of
      our study showed that in MBCL the MBC component was the predominant architectural
      finding and that there was confluence of MBCs in all but one case. In contrast,
      the MBC component did not predominate in the reactive group (P less than .000001)
      and focal confluence was seen in only one case. A cytologic comparison showed
      that in MBCL areas there were more large transformed (prominent nucleolated) MBCs
      (P = .003), a higher mitotic rate (P = .03), and more nuclear irregularities (P =
      .007) than were present in the reactive group. In addition, evolution to an
      aggressive histologic type was found in four cases of MBCL. Our results also
      revealed concomitant multiple, monoclonal, morphologically distinct populations
      in other compartments (follicular center cells in seven, mantle cells in five,
      small lymphocytes in five, and plasma cells in 11). These unique findings can be
      reconciled by postulating (1) that the simultaneous presence of these diverse
      cytologic types represents morphologic expressions of a B cell whose population
      is in different phases of its cell cycle and/or its evolution or (2) that the
      histogenesis of MBCL is possibly from a nodal pluripotent B-stem cell that can
      differentiate directly into these various cytologic types.

PMID- 1381335
TI  - Basal cell (basaloid) carcinoma of the lung: a new morphologic and phenotypic
      entity with separate prognostic significance.
AB  - On review of 115 poorly or undifferentiated lung cancers from 671 lung tumors
      resected over a 7-year period, we have found 38 cases of basaloid carcinoma. The
      cardinal histopathologic features distinguishing this tumor from other non-small
      cell lung cancers are a lobular growth pattern of small cells with moderately
      hyperchromatic nuclei, with no prominent nucleoli, and with scant cytoplasm, a
      high mitotic rate, and peripheral palisading. Basaloid carcinoma was present in a
      pure form in 19 cases and the other 19 tumors were of a mixed, but prominent,
      basaloid type associated with squamous cell carcinoma, large cell carcinoma, or
      adenocarcinoma. The immunophenotype of basaloid cancers was close to that of
      basal bronchial epithelial cells, with a low level of expression of low molecular
      weight cytokeratins. Staining for neuroendocrine markers was infrequent and
      inconsistent. Ultrastructural study showed an absence of neurosecretory granules
      and the presence of some squamous and/or glandular differentiation. This
      morphologic and immunologic phenotype suggests that basaloid carcinoma is derived
      from a pluripotent reserve cell or a basal bronchial epithelial stem cell. This
      unique histologic form of lung tumor has a poor prognosis, with a median survival
      rate of 22 months for stage I and II disease. This justifies classification of
      basaloid carcinoma as a distinct form of lung cancer, separate from small cell
      lung carcinoma.

PMID- 1381336
TI  - Modulation of norepinephrine release by galanin in rat medulla oblongata.
AB  - Galanin, a 29-amino acid peptide, is widely distributed in both the central and
      peripheral nervous systems and is colocalized with catecholamines, although its
      physiological significance remains to be elucidated. In the present study we
      investigated the regulatory mechanisms of galanin on norepinephrine release in
      rat medulla oblongata. In slices of medulla oblongata of Sprague-Dawley rats,
      galanin inhibited the stimulation-evoked [3H]norepinephrine release in a
      concentration-dependent manner (fractional release ratio during electrical
      stimulation: control 0.937 +/- 0.043, mean +/- SEM, n = 6; galanin 1 x 10(-7) M
      0.501 +/- 0.037, n = 6, p less than 0.05; and galanin 1 x 10(-6) M 0.299 +/-
      0.018 n = 6, p less than 0.05). Galanin potentiated inhibition of
      [3H]norepinephrine release by the alpha 2-agonists (UK 14,304 and clonidine). The
      blockade of alpha 2-adrenergic receptors by RX 781094 diminished the inhibition
      of norepinephrine release by galanin. Pretreatment of pertussis toxin, which
      interferes with the coupling of inhibitory guanosine triphosphate-binding
      proteins to adenylate cyclase, significantly attenuated the suppressive effects
      of galanin on norepinephrine release. In slices of medulla oblongata obtained
      from spontaneously hypertensive rats (SHR), the inhibitory effect of galanin on
      norepinephrine release was significantly less than in those from age-matched
      Wistar-Kyoto rats. These results show that galanin might inhibit the stimulation
      evoked norepinephrine release in rat medulla oblongata, at least partially
      mediated by alpha 2-adrenergic receptors and the pertussis toxin-sensitive
      guanosine triphosphate-binding proteins. Moreover, less suppression of
      norepinephrine release by galanin in SHR suggests that galanin might be involved
      in the regulation of central sympathetic nervous activity in hypertension.

PMID- 1381338
TI  - Treatment of chronic hepatitis.
AB  - Chronic hepatitis is an etiologically diverse syndrome. The approach to treatment
      depends on the cause of the disease. The efficacy of immunosuppressive treatment
      of chronic autoimmune hepatitis has long been established, and most patients with
      this disease can be treated successfully with prednisone and azathioprine.
      Interferon therapy has revolutionized the treatment of chronic viral hepatitis.
      Although the response in chronic hepatitis delta is disappointing, hepatitis C is
      often controlled, and certain patients with chronic hepatitis B may actually be
      cured of the disease. Future studies will seek to optimize the therapeutic
      effects of interferon in these viral diseases. Certainly, studies with other
      antiviral agents and biologic response modifiers are forthcoming. We have entered
      a new era in the treatment of chronic liver disease. It is reasonable to hope and
      expect that progress will continue and that most forms of chronic viral hepatitis
      will become curable within the next several years.

PMID- 1381337
TI  - Calcium channel activation in arterioles from genetically hypertensive rats.
AB  - Enhanced contractile responsiveness to the calcium channel agonist Bay K 8644 has
      been documented in large conduit arteries and small muscular arteries from
      hypertensive rats. The present study examined the effects of Bay K 8644 on the
      intracellular calcium concentration ([Ca2+]i) in microvessels from stroke-prone
      spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Using
      microspectrofluorometry of fura-2, [Ca2+]i was measured in smooth muscle cells
      localized on arteriolar fragments (15-35 microns external diameter) isolated
      after collagenase digestion of the pancreas. Resting [Ca2+]i in hypertensive
      arterioles (94 +/- 6 nM, n = 29) did not differ from that in normotensive vessels
      (81 +/- 4 nM, n = 40). KCl (50 mM), applied alone and in the presence of Bay K
      8644 (30 nM), stimulated increases in [Ca2+]i that were reversed in calcium-free
      solution and with nifedipine (10 microM), consistent with activation of potential
      operated calcium channels. Potassium-induced calcium transients were consistently
      potentiated by Bay K 8644. The change in [Ca2+]i evoked by KCl alone or in
      combination with Bay K 8644 did not differ between arterioles from hypertensive
      and normotensive rats. In 24% of the vessels from hypertensive rats and in 29% of
      those from normotensive rats, Bay K 8644 evoked an increase in [Ca2+]i that did
      not differ significantly between the two strains. The findings indicate that, in
      contrast to observations made in larger arteries, there is no evidence of a
      functional abnormality in potential-operated calcium channels in very small
      arterioles from genetically hypertensive rats.

PMID- 1381339
TI  - Cisplatin-based chemotherapy in advanced adenoid cystic carcinoma of the head and
      neck.
AB  - Nineteen patients, nine men and 10 women, with advanced adenoid cystic carcinoma
      (ACC), were treated with cisplatin either alone or in combination with
      doxorubicin and bleomycin. Median age was 51 years (range: 32-73 years). Two
      groups of patients were distinguished: Group 1 (N = 10) received single-agent
      cisplatin (50-120 mg/m2 IV every 4 weeks) for locoregional recurrence (N = 4),
      pulmonary metastases (N = 5), or as neoadjuvant therapy (N = 1). Five patients
      failed previous chemotherapy. No objective responses were observed, five patients
      showed stabilization of their disease for a median duration of 20 months (range:
      3-50 months). Group 2 (N = 9) received a combination of cisplatin (20 mg/m2 IV on
      days 1-5), doxorubicin (50 mg/m2 IV on day 1), and bleomycin (30 mg IV on days 1
      5), every 3 weeks. A complete remission (CR) was seen in one patient, lasting for
      2 years, a partial remission (PR) in two patients (duration: 6 months and 6
      years) (33%), and a stable disease (SD) in five patients (median duration: 15
      months; range 3-24 months). One patient showed progression from the start. The
      observed toxicity was acceptable: dose reduction was required in five patients
      for myelosuppression or impairment of renal function; vomiting grade III (WHO)
      was seen in 10 patients. The median progression-free survival was 36 months
      (range: 7-77 months). Median overall survival was 81 months (range: 14-216
      months). The role of cisplatin in this disease remains questionable.

PMID- 1381341
TI  - CD7 expression in malignant pleural mesothelioma.
AB  - CD7 antigen was found to be expressed on malignant mesothelioma arising from the
      right pleura in a 15-year-old girl not only by immunostaining using monoclonal
      antibodies, but also by Northern blot analysis. The level of expression in this
      tumor was comparable to those in T-cell lines, Jurkat and CCRF-CEM. Cytogenetic
      analysis of the tumor showed hypodiploidy (n = 43). CD7 has been regarded as one
      of the hematopoietic cell markers selectively expressed on the majority of T
      cells and multipotential stem cells. To our knowledge, this is the first report
      of a non-hematopoietic tumor expressing CD7.

PMID- 1381340
TI  - Low frequency of rearrangements of the ret and trk proto-oncogenes in Japanese
      thyroid papillary carcinomas.
AB  - We investigated the frequency of rearrangements of the ret and trk proto
      oncogenes in Japanese thyroid tumors. DNAs from 38 thyroid papillary carcinomas
      and 14 follicular adenomas were analyzed by Southern blotting. Rearrangements of
      the ret and trk proto-oncogenes were detected in one and two papillary
      carcinomas, respectively, but not in follicular adenomas. Analysis by a reverse
      transcriptase-polymerase chain reaction method showed that the ret rearrangement
      positive tumor contained the PTC/retTPC chimeric transcript, which was reported
      to be found specifically in thyroid tumors and adenomatous goiter. We also found
      that rearranged mRNA of the trk proto-oncogene was expressed at high levels in
      one of two trk rearrangement-positive tumors. Our results indicated that the
      frequency of rearrangements of these proto-oncogenes in Japanese papillary
      carcinomas was much lower than that in Italian patients.

PMID- 1381343
TI  - WS9326A, a novel tachykinin antagonist isolated from Streptomyces violaceusniger
      no. 9326. I. Taxonomy, fermentation, isolation, physico-chemical properties and
      biological activities.
AB  - Data from several studies suggest that tachykinins may play an important role in
      the pathophysiology of airway diseases, especially asthma. Our aim is to discover
      tachykinin antagonists which exhibit therapeutically useful anti-asthmatic
      activity. In our search for activities inhibiting the binding of [3H]substance P
      to guinea-pig lung membrane preparations, we have found that the fermentation
      product, WS9326A, isolated from Streptomyces violaceusniger, is a potent
      tachykinin receptor antagonist.

PMID- 1381342
TI  - Granulocyte-colony-stimulating factor enhances the circulating hematopoietic
      progenitors in lung cancer patients treated with cisplatin-containing regimens.
AB  - A phase II study examining the effects of human recombinant granulocyte-colony
      stimulating factor (G-CSF) on the growth of colony-forming unit-granulocyte
      macrophage (CFU-GM) in the bone marrow and in the peripheral blood was performed
      in lung cancer patients treated with cisplatin-containing regimens. Treatment
      with G-CSF following chemotherapy significantly increased the absolute
      granulocyte count. No significant effect of G-CSF on either the platelet or the
      red blood cell count was observed. Treatment with G-CSF did not affect the CFU-GM
      levels in the bone marrow, but did have a significant effect on peripheral blood
      CFU-GM levels 14 days after initiation of chemotherapy (P less than 0.05). Four
      patients demonstrated a rebound increase in the level of peripheral blood CFU-GM
      during the first course of chemotherapy without G-CSF. In contrast, eight
      patients displayed increase in peripheral blood CFU-GM levels during the second
      course of chemotherapy with G-CSF treatment. These findings demonstrate that G
      CSF is a potent stimulator of granulocyte proliferation as well as a potent agent
      for promoting transport of hematopoietic progenitors from the bone marrow into
      the peripheral blood.

PMID- 1381344
TI  - WS9326A, a novel tachykinin antagonist isolated from Streptomyces violaceusniger
      no. 9326. II. Biological and pharmacological properties of WS9326A and tetrahydro
      WS9326A (FK224)
AB  - WS9326A binds competitively to [3H]substance P (NK-1 receptor) binding sites on
      guinea-pig lung membranes (IC50 = 3.6 x 10(-6) M), and acts as a tachykinin
      antagonist in various functional assays. WS9326A inhibited tracheal constrictions
      produced by exogenously added substance P and neurokinin A, with IC50 values of
      9.7 x 10(-6) M and 3.5 x 10(-6) M, respectively. WS9326A inhibited neurokinin A
      induced bronchoconstriction in a dose dependent manner when administered to
      guinea-pigs intravenously together with neurokinin A, and was also effective in
      preventing capsaicin-induced bronchoconstriction, which is known to be caused by
      release of endogenous tachykinins (substance P and neurokinin A). FK224
      (tetrahydro-WS9326A; catalytic hydrogenation of WS9326A gave FK224) was more
      potent than WS9326A in the [3H]substance P receptor binding assay using guinea
      pig lung membrane (IC50 = 1.0 x 10(-7) M).

PMID- 1381345
TI  - Inhibition of angiogenesis by staurosporine, a potent protein kinase inhibitor.
AB  - The effect of staurosporine, a potent inhibitor of protein kinases, on embryonic
      angiogenesis was studied in an in vivo assay system involving chorioallantoic
      membranes of growing chick embryo. Staurosporine inhibited embryonic angiogenesis
      in a dose-related manner, the ID50 value being 71 pmol/egg. Staurosporine dose
      dependently suppressed the proliferation of vascular endothelial cells, an
      important event involved in the angiogenesis process. The IC50 value was 0.88 nM.
      In contrast, staurosporine did not affect the migration of vascular endothelial
      cells. These results suggest that staurosporine affected embryonic angiogenesis
      probably by inhibiting endothelial cell proliferation. In addition, these results
      might support the notion that certain protein kinase(s) could be implicated in
      induction of angiogenesis and also that staurosporine would be a useful compound
      for studying a mode of action of angiogenesis occurring in various diseases,
      including tumor development.

PMID- 1381346
TI  - Use of the polymerase chain reaction and oligonucleotide probes for the rapid
      detection and identification of Carnobacterium species from meat.
AB  - The polymerase chain reaction (PCR) was used selectively to amplify specific rDNA
      sequences of Carnobacterium divergens, C. mobile, C. piscicola and C. gallinarum
      in purified DNA extracts, crude cell lysates and food samples. The PCR products
      were visualized by agarose gel electrophoresis and identified, at species level,
      by hybridization reactions with three specific oligonucleotide probes for C.
      divergens, C. mobile and C. piscicola/C. gallinarum designed from 16S rRNA
      sequence data. The PCR was sufficiently sensitive to amplify DNA from a single
      bacterium to detectable levels after 30 cycles of amplification. Both radioactive
      (32P) and non-radioactive alkaline phosphatase labelled probes was able to detect
      the PCR products. Detection was highly specific and the probes did not hybridize
      with DNA samples from any other of the bacterial species tested. These methods
      enabled the rapid and specific detection and identification of carnobacteria from
      pure cultures and samples of meat.

PMID- 1381347
TI  - RNA catalysis by a group I ribozyme. Developing a model for transition state
      stabilization.

PMID- 1381348
TI  - Insulin and insulinomimetic agents induce activation of phosphatidylinositol 3'
      kinase upon its association with pp185 (IRS-1) in intact rat livers.
AB  - The major cytosolic substrate of the insulin receptor is a 185-kDa phosphoprotein
      (IRS-1) that contains multiple putative attachment sites for the p85 alpha
      regulatory subunit of phosphatidylinositol 3'-kinase (PI3K). To examine the
      possible interaction of pp185 with p85 alpha in vivo, we injected insulin or
      insulinomimetic agents (a combination of H2O2 and vanadate (H/V)) into the portal
      vein of anesthetized rats. IN this model system, H/V treatment and, to a lesser
      extent, injection of insulin resulted in rapid and sustained tyrosine
      phosphorylation of multiple cellular proteins, including pp185/IRS-1. The latter
      was found to undergo specific association with the p85 alpha regulatory subunit
      of PI3K but not with two other proteins that contain src homology domains. As p85
      alpha was not detectably phosphorylated on tyrosine residues and did not appear
      to interact directly with the insulin receptor, we conclude that tyrosine
      phosphorylation of pp185 promotes its association with p85 alpha and the
      catalytic subunit of PI3K. The recruitment of the holoenzyme may also involve its
      enzymatic activation and thus constitute an important step in the transduction of
      insulin signals.

PMID- 1381349
TI  - Identification of a sequence within the C-terminal 26 amino acids of cholesteryl
      ester transfer protein responsible for binding a neutralizing monoclonal antibody
      and necessary for neutral lipid transfer activity.
AB  - The cholesteryl ester transfer protein (CETP; 476 amino acids) mediates the
      transfer of neutral lipids and phospholipids between plasma lipoproteins.
      Previous studies showed that the epitope of a neutralizing monoclonal antibody
      (TP2) was located within the C-terminal 26 amino acids (aa) of CETP. To determine
      possible involvement of this region in lipid transfer activities, we generated
      six deletion mutants between Arg-451 and Leu-475 by in vitro mutagenesis and
      expressed mutant proteins in mammalian cells. Only deletion mutants between aa
      Phe-463 and Leu-475 failed to bind TP2; these mutant proteins were well secreted
      by cells but showed markedly reduced cholesteryl ester transfer activity. One of
      the deletion mutants (delta 470-475) showed similar reductions in cholesteryl
      ester and triglyceride transfer activities but normal or increased phospholipid
      transfer activity. Limited proteolysis of this mutant protein indicated a similar
      overall folding pattern to the wild-type protein. Thus, aa between Phe-463 and
      Leu-475 are necessary for binding TP2. Deletions within this sequence selectively
      impair neutral lipid transfer activity, suggesting a direct involvement in
      neutral lipid transfer.

PMID- 1381351
TI  - Up-regulation of surface CD34 is associated with protein kinase C-mediated
      hyperphosphorylation of CD34.
AB  - CD34 is a transmembrane sialoglycoprotein expressed by early hematopoietic
      progenitor cells as well as endothelial cells. Previously we found that CD34 is
      rapidly and stoichiometrically phosphorylated by activated protein kinase C (PKC)
      (Fackler, M.J., Civin, C.I., Sutherland, D.R., Baker, M.A., and May, W.S. (1990)
      J. Biol. Chem. 265, 11056-11061). In the present study, we find dose-dependent up
      regulation of CD34 surface expression following treatment of normal human CD34+
      bone marrow progenitor cells, cord blood-derived KMT-2, or KG1 a myeloid leukemia
      cells with the PKC activator 12-O-tetradecanoylphorbol-13-acetate. Up-regulation
      begins within 1 min of treatment, is maximal by 30 min, is maintained for at
      least 3 h, and is associated with CD34 hyperphosphorylation. A specific inhibitor
      of PKC, 2,6-diamino-N-(1[1-(1-oxotridecyl)-2-piperadinyl]methyl)h exan-amide (NPC
      15437), blocks both up-regulation and hyperphosphorylation of CD34. CD34 up
      regulation is independent of transcription and/or translation and results from
      the recruitment of preformed intracellular CD34. The endocytosis rate of surface
      CD34 is unaltered by 12-O-tetradecanoylphorbol-13-acetate. Thus, activation of
      PKC mediates increased surface expression of the CD34 molecule possibly as a
      result of phosphorylation of CD34.

PMID- 1381350
TI  - Functional analysis of HIV-1 reverse transcriptase amino acids involved in
      resistance to multiple nonnucleoside inhibitors.
AB  - Several novel, structurally distinct classes of specific human immunodeficiency
      virus type 1 (HIV-1) reverse transcriptase (RT) nonnucleoside inhibitors have
      been described recently. These include the pyridinone derivatives L-697,639, L
      697,661, and L-696,229 as well as BI-RG-587 and the tetrahydroimidazo[4,5,1-j,k]
      benzodiazepin-2(1H)-one and -thione compounds. Previous studies have implicated
      involvement of the RT amino acid residues at positions 103, 181, and 188 in the
      activity of the compounds. Accordingly, HIV-1 RT mutants containing a series of
      amino acid substitutions at these positions were constructed. The relative
      resistance of purified mutant enzymes to each of the inhibitors was assessed.
      This analysis established the functional equivalence of the three inhibitor
      classes and provided evidence for the interaction of the 103 site with the
      181/188 region. Amino acid substitutions at these positions were also found to
      influence RT sensitivity to inhibition by phosphonoformate, thereby suggesting a
      close association between this pyrophosphate analog's binding site in RT and the
      binding site of the nonnucleoside inhibitors. In addition, aromatic stacking of
      the amino acid side groups at residues 181 and 188 was suggested to be required
      for inhibitor activity.

PMID- 1381352
TI  - Distinct properties of the recognition sites for beta-very low density
      lipoprotein (remnant receptor) and alpha 2-macroglobulin (low density lipoprotein
      receptor-related protein) on rat parenchymal cells.
AB  - The properties of the recognition sites for alpha 2-macroglobulin (alpha 2
      macroglobulin receptor; low density lipoprotein receptor-related protein) and
      beta-migrating very low density lipoprotein (beta-VLDL) (remnant receptor) on rat
      parenchymal cells were directly compared to analyze whether both substrates are
      recognized and internalized by the same receptor system. In cholesterol-fed rats,
      the large circulating pool of beta-VLDL is unable to diminish the liver uptake of
      125I-labeled alpha 2-macroglobulin, while liver uptake of 125I-labeled beta-VLDL
      in these rats is reduced by 87.3% at 10 min after injection. In vitro competition
      studies with isolated parenchymal liver cells demonstrate that the binding of
      125I-labeled alpha 2-macroglobulin to rat parenchymal cells is not effectively
      competed for by beta-VLDL, whether this lipoprotein is additionally enriched in
      apolipoprotein E or not. Binding of alpha 2-macroglobulin to parenchymal cells
      requires the presence of calcium, while binding of beta-VLDL does not. Incubation
      of parenchymal cells for 1 h with proteinase K reduced the subsequent binding of
      alpha 2-macroglobulin by 90.1%, while the binding of beta-VLDL was reduced by
      only 20.2%. In the presence of monensin, the association of alpha 2-macroglobulin
      to parenchymal cells at 2 h of incubation was reduced by 64.7%, while the
      association of beta-VLDL was not affected. Preincubation of parenchymal cells
      with monensin for 60 min at 37 degrees C reduced the subsequent binding of alpha
      2-macroglobulin by 54.5%, while binding of beta-VLDL was only reduced by 14.6%.
      The results indicate that the recognition sites for alpha 2-macroglobulin and
      beta-VLDL on rat parenchymal cells do exert different properties and are
      therefore likely to reside on different molecules.

PMID- 1381353
TI  - Human placental brush-border membrane Na(+)-biotin cotransport.
AB  - Membrane transport pathways for transplacental transfer of the water-soluble
      vitamin biotin were investigated by assessing the possible presence of a Na(+)
      biotin cotransport mechanism in the maternal-facing membrane of human placental
      epithelial cells. The presence of Na(+)-biotin cotransport was determined from
      radiolabeled tracer flux measurements of biotin uptake using preparations of
      purified brush-border membrane vesicles. The imposition of an inwardly directed
      Na+ gradient stimulated vesicle uptake of biotin to levels approximately 25-fold
      greater than those observed at equilibrium. The voltage sensitivity of Na+
      gradient-driven biotin uptake suggested Na(+)-biotin cotransport is electrogenic
      occurring with net transfer of positive charge. A kinetic analysis of the
      activation of biotin uptake by increasing Na+ was most consistent with an
      interaction of Na+ at 2 sites in the transport protein. Static head
      determinations used to identify the magnitude of opposing driving forces bringing
      flux through the cotransport mechanism to equilibrium indicated a coupling ratio
      of 2 Na+ per biotin. Substrate specificity studies using chemical analogues of
      biotin suggested both the terminal carboxylic acid of the valeric acid side chain
      and a second nucleus of anionic charge were important determinants for substrate
      interaction with the cotransport protein. Initial rate determinations of biotin
      uptake indicate biotin interacts with a single saturable site (Km = 21 microM)
      with a maximal transport rate of 4.5 nmol/mg/min. The results of this study
      provide evidence for an electrogenic Na(+)-biotin cotransport mechanism in the
      maternal-facing membrane of human placental epithelial cells.

PMID- 1381354
TI  - Regulation of expression of the neuronal POU protein Oct-2 by nerve growth
      factor.
AB  - POU proteins are a class of homeobox-containing transcription factors that
      regulate tissue-specific gene expression and influence cell differentiation and
      function. We have investigated the possible role of such factors in mediating the
      actions of nerve growth factor (NGF) on sensory neurons. NGF has been found to
      have differential effects on the levels of three POU protein transcription
      factors that are expressed in adult rat sensory neurons. A sensory neuron octamer
      binding protein with the properties of the transcription factor Oct-2 is up
      regulated 3-4-fold by NGF, as measured by mobility shift assays using nuclear
      extracts from adult rat dorsal root ganglion neurons grown in the presence or
      absence of NGF. Quantitation of Oct-2 mRNA by polymerase chain reaction
      amplification of RNA from such cells shows a parallel increase in Oct-2 mRNA
      levels. In contrast, the levels of mRNA encoding the ubiquitous POU protein Oct-1
      or the neuron-specific POU protein Brn-3, also present in sensory neurons, are
      unaffected by NGF. These observations suggest a role for Oct-2 in mediating
      transcriptional effects induced by NGF. In particular, as Oct-2 is known to
      inhibit herpes simplex virus immediate-early gene expression in neuronal cells,
      these findings provide a mechanism for the known action of NGF in the maintenance
      of latent herpes virus infections in sensory neurons.

PMID- 1381355
TI  - Structure/function studies on vascular cell adhesion molecule-1.
AB  - Vascular cell adhesion molecule-1 (VCAM1) is a member of the immunoglobulin (Ig)
      superfamily which interacts with the integrin very late antigen-4 (VLA4). The
      VCAM1/VLA4 interaction mediates both adhesion and signal transduction and is
      thought to play an important role in inflammatory and immune responses in vivo.
      The major form of human VCAM1 contains seven extracellular Ig-like domains, with
      domain 1 designated as the most N-terminal. We have examined the relationship
      between human VCAM1 structure and function using a combination of domain
      truncation mutants and proteolytic fragmentation of recombinant soluble VCAM1. We
      have characterized two regions of VCAM1, localized to domains 4 and 5, which are
      highly sensitive to proteolytic cleavage, localized the epitope of the blocking
      monoclonal antibody 4B9 to domain 1, and found that domains 1-3 are sufficient
      for both its adhesive function and its ability to initiate T cell activation.

PMID- 1381356
TI  - Structure of the gene for human transglutaminase 1.
AB  - Transglutaminase 1 (TG1) is an enzyme that is expressed and activated during
      terminal differentiation of keratinocytes and synthesizes cornified envelope by a
      cross-linking reaction. The gene encoding human TG1 was isolated from human
      genomic DNA and characterized. It spans 14.3 kilobase pairs and is composed of 15
      exons. All exon-intron junctional sequences conformed to the canonical GT-AG
      rule. The translation start was located in the second exon. The active site Cys
      residue of the enzyme was in exon 7. The coding sequence for human TG1 was
      comprised of 2454 nucleotides identical with the published human TG1-cDNA
      sequence (Yamanishi, K., Liew, F.-M., Konishi, K., Yasuno, H., Doi, H., Hirano,
      J., and Fukushima, S. (1991) Biochem. Biophys. Res. Commun. 175, 906-913). The
      sizes of exons from 3 to 14 were markedly conserved between the genes for the
      human TG1 and factor XIIIa, another member of the transglutaminase family. The
      one major and two minor transcription initiation sites of the TG1 gene were
      determined by primer extension. The 5'-flanking region of the human TG1 gene
      showed features of a housekeeping gene and contained potential regulatory motifs,
      including elements found in keratinocyte-related genes. The chromosome
      sublocalization of the TG1 gene was assigned to 14q11.2.

PMID- 1381357
TI  - Sp1 DNA binding efficiency is highly reduced in nuclear extracts from aged rat
      tissues.
AB  - To explore the role of transcriptional factors in the genesis of the senescent
      phenotype, nuclear extracts from 4- and 30-month-old rat brains were analyzed for
      the presence of DNA-binding proteins able to interact with double-stranded
      oligonucleotides containing recognition sites for sequence-specific DNA-binding
      factors. Gel shift assays revealed that the DNA-binding efficiency of Sp1 is
      significantly reduced in aged animals compared to young ones, whereas CTF/NF1 and
      AP1 from young and old rat nuclear extracts bind their DNA targets with the same
      efficiency. The quantitative analysis of Sp1 by immunoblotting indicated that
      equivalent quantities and degrees of heterogeneity of Sp1 protein are present in
      both nuclear extracts, suggesting that the observed difference is not due to a
      different expression of this transcriptional factor. DNase I footprinting of the
      heavy chain ferritin gene promoter, which contains a Sp1 binding site,
      demonstrated that the nuclear extract from 30-month-old rat brain does not
      protect the region involved in the regulation of the H ferritin gene by Sp1. This
      results in a reduction of about 50% of the expression of the H ferritin mRNA in
      aged rat brains. Furthermore, the Sp1 binding sites present in the SV40 early
      promoter are not protected in a DNase I footprinting assay where a nuclear
      extract from 30-month-old rat brain was used as a source of DNA binding proteins.
      Liver nuclear extracts prepared from young and aged rats demonstrated that a
      decrease of Sp1 binding efficiency is similarly present in this tissue.

PMID- 1381358
TI  - Cysteine synthase from Capsicum annuum chromoplasts. Characterization and cDNA
      cloning of an up-regulated enzyme during fruit development.
AB  - Cysteine synthase (O-acetylserine sulfhydrylase) has been purified to homogeneity
      from bell pepper (Capsicum annuum) fruit chromoplasts. This enzyme consists of
      two subunits of 35 kDa. Immunocytochemical localization experiments confirmed the
      plastid location of this enzyme. A full-length cDNA was isolated from an
      expression library of C. annuum. The deduced peptide sequence revealed high
      similarity between the C. annuum cysteine synthase and its bacterial
      counterparts. In vitro transcription and translation of the cDNA and subsequent
      import experiments demonstrated that the encoded cysteine synthase is located in
      the plastids. The steady-state level of the cysteine synthase mRNA is almost
      constant in dark-grown hypocotyls, leaves, and fruits. However, a slight increase
      in this mRNA level was detected during fruit development (when the 25 S rRNA was
      taken as an internal standard). Similarly, the cysteine synthase activity in
      plastids was found to increase during fruit development and reaches the highest
      levels in the chromoplasts of red fruits. To address the physiological role of
      this phenomenon, we have shown that cysteine is engaged in the active metabolism
      of glutathione. Thus, in connection with the previous demonstration of an active
      tocopherol metabolism, it is concluded that differentiation of chloroplast to
      chromoplast in C. annuum involves an active synthesis of potential antioxidants
      or redox modulators.

PMID- 1381359
TI  - Transcriptional activation of the tumor necrosis factor alpha-inducible zinc
      finger protein, A20, is mediated by kappa B elements.
AB  - A20 was first identified as a tumor necrosis factor (TNF) primary response
      transcript encoding a 790-amino acid protein with a unique zinc finger motif.
      Recently, A20 was shown to protect cells from TNF-induced cytotoxicity in a
      variety of cell lines. Nuclear run-on studies previously established that TNF
      activates A20 at the transcriptional level. To further characterize the mechanism
      by which TNF activates the A20 gene, we have cloned the A20 5'-flanking sequences
      and identified TNF-responsive elements within the promoter. The transcription
      initiation site was mapped by both primer extension and S1 nuclease protection
      experiments to a position 4.2 kilobases (kb) upstream of the initiator
      methionine; the first and second exon were separated by a 3.9-kb intron.
      Sequences upstream of the transcription start site were 76% GC-rich and contained
      six Sp1 binding sites and a TATA-like sequence at -29 but lacked a consensus
      CCAAT site. Transfection of Jurkat T-cells with an array of A20 promoter CAT
      constructs showed that two kappa B elements residing at -54 and -66 were required
      for induction by TNF. Supporting this notion, DNA electrophoretic mobility shift
      assays using nuclear extracts from unstimulated and TNF-stimulated Jurkat cells
      demonstrated kappa B-specific binding of a TNF-activated factor to an end-labeled
      probe containing the two A20 kappa B sequences. Finally, evidence obtained from
      cotransfection experiments showed that A20 negatively regulated its own
      expression.

PMID- 1381360
TI  - Steel factor stimulates the tyrosine phosphorylation of the proto-oncogene
      product, p95vav, in human hemopoietic cells.
AB  - Steel factor (SF) (also called stem cell factor, mast cell growth factor, or c
      kit ligand) is a recently cloned hemopoietic growth factor that is produced by
      bone marrow stromal cells, fibroblasts, and hepatocytes. In both mouse and man it
      acts synergistically with several colony stimulating factors, including
      interleukin-3 (IL-3) and granulocyte macrophage-colony stimulating factor (GM
      CSF), to induce the proliferation and differentiation of primitive hemopoietic
      precursor cells. In order to study its mechanism of action and to explore the
      molecular basis for its synergistic activity we have examined the proteins that
      become tyrosine phosphorylated in response to SF, IL-3, and GM-CSF. We report
      herein that SF, but not IL-3 or GM-CSF, dramatically stimulates the tyrosine
      phosphorylation of the product of the recently discovered proto-oncogene, vav, in
      two SF-responsive human cell lines, M07E and TF-1. Although phosphorylation is
      very rapid, reaching maximal levels within 2 min at 37 degrees C, co
      immunoprecipitation studies suggest that c-kit may either not associate directly
      with p95vav or bind to it with very low affinity. Nonetheless, our data suggest
      that c-kit may utilize p95vav to mediate downstream signaling in hemopoietic
      cells.

PMID- 1381361
TI  - Cyclic AMP and calcium regulate at a transcriptional level the expression of the
      CD7 leukocyte differentiation antigen.
AB  - CD7 is a 40-kDa cell surface glycoprotein expressed on T-cell precursors before
      their entry into the thymus during fetal development and whose functional role
      remains uncertain. T-cell activation has been shown to increase the expression of
      this surface molecule. In this report we describe the intracellular signals and
      the mechanisms involved in the regulation of CD7 antigen expression on human T
      lymphocytes. The elevation of intracellular calcium by using the A23187 ionophore
      increased the cell surface expression of CD7, whereas protein kinase C activation
      caused its down-regulation. Interestingly, the increase of intracellular cAMP
      with Bt2cAMP stimulated CD7 expression as well. Upregulation of CD7 on the cell
      surface following either Bt2cAMP or calcium ionophore stimulation of T
      lymphocytes correlated with a raise of the steady-state levels of CD7-specific
      mRNA, without de novo protein synthesis requirements. No differences between the
      half-life of basal CD7 mRNA and that induced by either Bt2cAMP or calcium
      ionophore were detected. Run-on experiments showed that both stimuli enhanced the
      transcriptional rate of the CD7 gene. Our results provide the evidence for a
      positive regulatory effect mediated by cAMP on the expression of a leucocyte
      differentiation antigen.

PMID- 1381362
TI  - mdr2 encodes P-glycoprotein expressed in the bile canalicular membrane as
      determined by isoform-specific antibodies.
AB  - We have produced antibodies specific for the three P-glycoprotein (P-gp) isoforms
      encoded by the mouse mdr1, mdr2, and mdr3 genes. The anti-Mdr2 and anti-Mdr3
      antibodies were generated against synthetic peptides derived from the "linker"
      region, whereas the anti-Mdr1 antibody was raised against a fusion protein
      containing the amino terminus of Mdr1. Western blot analysis showed that the
      three antibodies could discriminate between the three isoforms in membrane
      fractions from Hamster cells transfected with the corresponding full-length or
      chimeric mdr cDNAs. Immunocytochemistry studies of mdr-transfected cells showed
      that the three antibodies specifically recognized each P-gp isoform expressed in
      whole cells. Immunoblotting of normal mouse tissues revealed that the Mdr2
      isoform was expressed at very high levels in liver canalicular membrane vesicles
      (CMV) but not in membrane vesicles prepared from the basolateral (sinusoidal)
      domain (SMV). Mdr3 was detected in intestinal brush border membrane vesicles and
      also in CMV, although at levels much lower than Mdr2. Mdr1 was not detected in
      CMV or SMV but was detected in endometrial tissue from the gravid uterus.
      Photolabeling experiments with [125I]iodoarylazidoprazosin followed by
      immunoprecipitation with isoform-specific antibodies indicated that, in CMV, Mdr3
      but not Mdr2 could bind the drug analogue.

PMID- 1381363
TI  - Chemoattractant-induced tyrosine phosphorylation and activation of microtubule
      associated protein kinase in human neutrophils.
AB  - Activation of human neutrophils by the chemotactic peptide formyl-methionyl
      leucyl-phenylalanine (fMLP) induces tyrosine phosphorylation of several
      polypeptides, including a prominent band of approximately 41 kDa. A polypeptide
      of identical electrophoretic mobility was recognized by a monoclonal antibody
      raised against a sequence corresponding to amino acids 325-345 of ERK-1, one of a
      family of mitogen-activated protein (MAP) kinases. To establish the possible
      identity of these polypeptides, extracts from control and fMLP-treated cells were
      immunoprecipitated with immobilized antiphosphotyrosine antibodies. Reactivity
      with anti-ERK-1 antibodies was observed only in the precipitate of
      chemoattractant-stimulated cells. These data imply that a MAP kinase constitutes
      at least part of the tyrosine-phosphorylated 41-kDa polypeptide. By using an in
      vitro renaturation assay, treatment of intact cells with fMLP was found to
      stimulate several protein kinases, including one of approximately 41 kDa.
      Renaturation of samples immunoprecipitated with antiphosphotyrosine antibodies
      revealed the presence of an active protein kinase in chemoattractant-stimulated,
      but not in control cells. The immunoprecipitated kinase comigrated with the 41
      kDa tyrosine phosphorylated polypeptide and the anti-ERK-1 reactive band. We
      conclude that a MAP kinase closely related or identical to ERK-1 is tyrosine
      phosphorylated and activated when human neutrophils are stimulated by chemotactic
      peptides. The rapid phosphorylation of this kinase, which is apparent within
      seconds, is compatible with a role in the activation of the respiratory burst
      and/or other neutrophil responses.

PMID- 1381364
TI  - Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase
      of human liver.
AB  - Fifty human livers obtained at autopsy were analyzed for N-acetyltransferase and
      classified into six genotypes. Determination of N-acetyltransferase activity and
      proteins from supernatants of liver homogenates indicate that genotype I
      corresponds to rapid acetylator, genotypes II and III to intermediate acetylator,
      and genotypes IV, V, and VI to slow acetylator phenotypes. Northern blot analysis
      shows that levels of mRNA for N-acetyltransferase in the livers do not markedly
      differ among the six genotypes. Three alleles of the N-acetyltransferase gene
      were cloned and sequenced. mRNA is coded in two exons. Comparison of alleles 2
      and 3, which correspond to low N-acetyltransferase activity, with allele 1, which
      corresponds to high N-acetyltransferase activity, revealed several polymorphisms.
      Two gene sequence differences occur in the coding exons of alleles 2 and 3, one
      of which would produce different amino acids in the proteins. Those sequence
      differences that lead to amino acid substitutions result in a loss of BamHI and
      TaqI sites for alleles 2 and 3, respectively. Expression studies of the alleles
      in Chinese hamster ovary cells show that allele 1 expresses high levels of N
      acetyltransferase activity and enzyme protein, while alleles 2 and 3 express low
      levels of both protein and activity.

PMID- 1381365
TI  - Characterization and epitope mapping of monoclonal antibodies directed against
      the beta' subunit of the Escherichia coli RNA polymerase.
AB  - Monoclonal antibodies (mAbs) raised against the beta' subunit of the Escherichia
      coli RNA polymerase were used to probe the structure and function of this
      subunit. Of the five anti-beta' monoclonal antibodies studied, only mAb 311G2 is
      a strong inhibitor of RNA polymerase activity. This antibody binds to an epitope
      which is exposed in both the assembled holoenzyme and isolated beta' subunit. In
      contrast, the null antibodies bind to the free beta' subunit but very weakly to
      native RNA polymerase. It would appear that the beta' domain in which their
      epitopes reside is either conformationally altered or blocked due to interaction
      with other subunits in native RNA polymerase. In order to locate the positions of
      the epitopes for these five monoclonal antibodies, a series of overlapping
      deletion mutants have been constructed by partial restriction and religation of
      the beta' gene present in pT7 beta' (Zalenskaya, K., Lee, J., Gujuluva, C. N.,
      Shin, Y. K., Slutsky, M., nd Goldfarb, A. (1990) Gene 89, 7-12). The presence of
      the epitopes for each of the anti-beta' monoclonal antibodies was assessed by
      Western blotting. The results indicate that the epitopes for mAb 340F11, mAb
      370F3, mAb 371D6, and mAb 372B2 are located between amino acids 817-876. This
      region may be important in enzyme assembly or subunit-subunit interaction. The
      epitope for the inhibitory antibody, mAb 311G2, is located between amino acids
      1047-1093. This region may be involved in the catalytic function of RNA
      polymerase.

PMID- 1381366
TI  - Urokinase plasminogen activator cleaves its cell surface receptor releasing the
      ligand-binding domain.
AB  - The cellular receptor for urokinase-type plasminogen activator (uPAR) is a
      glycolipid-anchored three-domain membrane protein playing a central role in
      pericellular plasminogen activation. We have found that urokinase (uPA) can
      cleave its receptor between domains 1 and 2 generating a cell-associated uPAR
      variant without ligand-binding properties. In extracts of U937 cells there are
      two uPAR variants which after complete deglycosylation have apparent molecular
      masses of 35,000 and 27,000. Analysis with monoclonal antibodies showed that
      these variants represented the intact uPAR and a two-domain form, uPAR(2+3),
      lacking ligand-binding domain 1. Trypsin treatment showed that both variants are
      present on the outside of the cells. Addition to the culture medium of an
      anticatalytic monoclonal antibody to uPA inhibited the formation of the
      uPAR(2+3), indicating that uPA is involved in its generation. Purified uPAR can
      be cleaved directly by uPA as well as by plasmin. The uPA-catalyzed cleavage does
      not require binding of the protease to the receptor through its epidermal growth
      factor-like receptor-binding domain, since low molecular weight uPA that lacks
      this domain also cleaves uPAR. This unusual reaction in which a specific binding
      protein is proteolytically inactivated by its own ligand may represent a
      regulatory step in the plasminogen activation cascade.

PMID- 1381367
TI  - CD36 peptides enhance or inhibit CD36-thrombospondin binding. A two-step process
      of ligand-receptor interaction.
AB  - CD36 (glycoprotein IV or IIIB) is an integral plasma membrane protein of wide
      cellular distribution and functions as a receptor site for thrombospondin (TSP),
      an adhesive protein important in cell-cell and cell-matrix interactions. OKM5, a
      monoclonal anti-CD36 antibody, has been reported to block CD36 cell adhesive
      functions suggesting that the OKM5 epitope on CD36 is functionally important. A
      panel of 10 synthetic CD36 peptides was made. One peptide, P139-155, specifically
      inhibited the immunoadsorption of CD36 by OKM5, and P139-155 was directly
      immunoadsorbed by OKM5, indicating that CD36 sequence 139-155 represents part of
      the OKM5 epitope. TSP bound to immobilized P139-155 in a dose-dependent and
      saturable manner. Surprisingly, P139-155 significantly augmented, instead of
      inhibited, binding of CD36 to TSP. This peptide did not induce platelet
      aggregation but augmented ADP- and collagen-induced aggregation in platelet-rich
      plasma. Another CD36 peptide, P93-110, which had no effect on OKM5
      immunoadsorption, blocked binding of CD36 to immobilized TSP and partially
      inhibited collagen-induced platelet aggregation. P93-110 by itself did not bind
      to TSP; however, in the presence of P139-155, there was a marked enhancement of
      P93-110 binding to TSP, with a stoichiometry consistent with the trimeric nature
      of TSP. The data suggest that CD36-TSP interaction is a two-step process; the
      sequence 139-155 region of CD36 binds first to TSP, triggering a change in TSP to
      reveal a second site, which binds the 93-110 region of CD36 with high affinity.
      CD36 peptides can be used as stimulators or inhibitors in cellular adhesive
      events involving TSP-CD36 interaction. Conformational changes leading to the
      exposure or activation of high affinity binding sites may occur in both the
      receptor and the ligand upon cell-cell and cell-matrix adhesion.

PMID- 1381368
TI  - Analysis of the interaction between an alpha (1----6)dextran-specific mouse
      hybridoma antibody and dextran B512 by affinity electrophoresis.
AB  - Carbohydrates are common environmental antigens. As dextran B512 is composed of a
      repeating structure of simple antigenic determinants, it is widely used to study
      the immunochemical properties of immunoglobulins. Two-dimensional affinity
      electrophoresis patterns of a mouse monoclonal antidextran antibody (35.8.2H;
      IgG1, BALB/c) were produced to obtain insights into the microheterogeneity of the
      monoclonal antibody. The monoclonal antibody was separated into about six spots
      which had an identical affinity to dextran B512, but differed in their
      isoelectric points (pI). In addition, the pH dependence of the binding affinity
      of this antidextran to dextran B512 was examined. By comparing affinities
      obtained by affinity electrophoresis between weakly basic (pH 9.5) and weakly
      acidic (pH 3.8) discontinuous buffer systems, the latter showed an affinity about
      500 times lower than the former. The change in the affinity was investigated with
      a continuous pH gradient by an affinity titration curve and was seen to change
      markedly at about pH 6. This suggests that the histidine at residue 34 in the
      light-chain CDR1 is largely responsible for the dextran binding.

PMID- 1381369
TI  - Cellulose bearing covalently linked copper phthalocyanine trisulphonate as an
      adsorbent selective for polycyclic compounds and its use in studies of
      environmental mutagens and carcinogens.
AB  - A method useful as a preconcentration technique for isolating mutagens and
      carcinogens is described. Cotton bearing covalently linked copper phthalocyanine
      trisulphonate as ligand (blue cotton) can adsorb selectively compounds having
      three or more fused rings. The adsorption takes place in aqueous media, involving
      1:1 complex formation between the ligand and the polycyclic compound. The
      desorption can be done by elution with organic solvents, most effectively with
      methanol containing ammonia. As many important environmental mutagens and
      carcinogens are polycyclics, this adsorption is useful as a means of extracting
      this class of materials from crude samples such as food, urine and river waters.
      The use of copper phthalocyanine as a ligand for chromatographic supports has
      recently been initiated, yielding promising results for the effective separation
      of polycyclic aromatic compounds from each other.

PMID- 1381370
TI  - Mapping of viral epitopes with conformationally specific monoclonal antibodies
      using biosensor technology.
AB  - An automated biosensor system (BIAcore) designed for measuring molecular
      interactions in real time and without labelling any of the reactants was used for
      mapping the epitopes of tobacco mosaic virus protein using conformationally
      specific monoclonal antibodies (MAbs). Some of the MAbs used as capturing
      antibody on the sensor chip allowed a conformational change to occur in the viral
      protein. As a result, MAbs specific for the quaternary structure of polymerized
      viral protein were able to bind to monomeric viral subunits. Compared with
      classical solid-phase enzyme immunoassay, the biosensor technology possesses
      several advantages for epitope mapping of viral proteins.

PMID- 1381371
TI  - Coexpression of renin, angiotensinogen, and their messenger ribonucleic acids in
      adrenal tissues.
AB  - The presence of the two components of the renin-angiotensin system (RAS) has been
      systematically investigated in human normal and pathological adrenal tissues with
      two aims: 1) the detection of renin and especially angiotensinogen, which has not
      been reported before; and 2) to study possible differences in the coexpression of
      renin and angiotensinogen in tissue of cortical and medullary origin. The
      relative levels of renin and angiotensinogen mRNAs were determined by Northern
      blot analysis in normal (n = 5) and pathological adrenal tissues of cortical (n =
      23) and medullary (n = 10) origin. Renin, prorenin, and angiotensinogen levels
      were also measured. Renin concentrations in normal and pathological adrenals were
      around 30-fold higher than those in the plasma of normal subjects, except for a
      Cushing's adenoma, which contains an extremely high renin content. Renin
      accounted for 56% of the total renin in normal adrenals and up to 87% in
      neoplastic tissues. This high proportion of renin indicates a likely conversion
      of prorenin to renin within these tissues. Renin mRNA was detected in each group
      of adrenal tissues. There was a significant correlation between the concentration
      of renin and its mRNA (r = 0.75; P less than 0.05). Angiotensinogen and its mRNA
      were detected in all normal and pathological adrenals. Compared to normal adrenal
      tissues, the relative amount of angiotensinogen mRNA was significantly higher in
      pheochromocytomas. However, the increased mRNA level in these tissues was not
      accompanied by a parallel increase in tissue angiotensinogen levels. Since the
      translational efficiency of angiotensinogen was verified by in vitro cell-free
      translation, the low level of angiotensinogen compared to the relatively high
      amount of its mRNA suggests a lack of storage of this protein in adrenal cells,
      as in liver cells. This study demonstrates that renin and angiotensinogen are
      coexpressed in normal and pathological tissues. Tissues of different cellular
      origin (zona glomerulosa, fasciculata, and medullary tissue), were able to
      express, store, and process renin and synthesize angiotensinogen. There was no
      obvious relationship between the expression of these proteins and the
      pathophysiology of the adrenal gland.

PMID- 1381372
TI  - The effect of anorexia nervosa and refeeding on growth hormone-binding protein,
      the insulin-like growth factors (IGFs), and the IGF-binding proteins.
AB  - We studied the relationship of serum insulin-like growth factor-I (IGF-I), IGF
      II, the IGF-binding proteins IGFBP-1, IGFBP-2, and IGFBP-3, and GH-binding
      protein (GHBP; which is postulated to be derived from the extracellular portion
      of the GH receptor) in normal volunteers and patients with anorexia nervosa
      before and after a refeeding program. Serum GHBP, IGF-I, and IGFBP-3 were all
      significantly decreased in low weight patients with anorexia nervosa and returned
      to nearly normal levels with refeeding. Fasting serum GH and serum IGFBP-1 and
      IGFBP-2 were significantly increased in low weight patients with anorexia nervosa
      and also returned to nearly normal levels with refeeding. Serum IGF-II was 27%
      lower in the low weight group than in normal subjects, but this difference was
      not statistically significant. Both serum IGF-I and IGF-II were positively
      correlated with serum IGFBP-3 and negatively correlated with serum IGFBP-1 and
      IGFBP-2. These data are consistent with the hypothesis that nutritional
      deprivation alters the GH-IGF axis by down-regulation of the GH receptor or its
      postreceptor mechanisms, and that this effect is reversible with refeeding.

PMID- 1381373
TI  - Major histocompatibility complex class I gene expression in rat thyroid cells is
      regulated by hormones, methimazole, and iodide as well as interferon.
AB  - Autoimmune thyroid disease is associated with enhanced expression of major
      histocompatibility complex class I antigens on thyrocytes. To better understand
      this phenomenon, we have studied the normal expression of class I genes in FRTL-5
      rat thyroid cells. A variety of hormones and growth factors that regulate the
      growth and function of these thyroid cells were found to decrease class I RNA
      levels: serum, insulin or insulin-like growth factor-I (IGF-I), and
      hydrocortisone. Antibody preparations from Graves' patients (thyroid-stimulating
      antibodies), which increase cAMP levels and stimulate the thyroid, also decrease
      class I RNA levels. This is consistent with the fact that TSH, via its cAMP
      signal, reduces class I transcripts. The class I response to TSH, serum, insulin,
      IGF-I, or hydrocortisone is specific, in that the same agents do not similarly
      affect TSH receptor, thyroglobulin, thyroid peroxidase, malic enzyme, or beta
      actin RNA levels. Both gamma- and alpha-interferon increase class I RNA levels in
      FRTL-5 cells, even in the presence of the serum, IGF-I, or hormones noted above,
      i.e. they overcome hormonal negative regulation in normal thyrocytes. In
      contrast, methimazole treatment of rat FRTL-5 thyroid cells, but not rat
      fibroblasts or rat FRT thyroid cells, which have no TSH receptor and no TSH
      regulated function, results in reduced class I RNA levels. The action of
      methimazole can inhibit interferon action, is transcriptional, is duplicated by
      iodide, and is additive with the negative regulatory action of hormones and serum
      factors, including TSH.

PMID- 1381374
TI  - Interleukin-1 beta stimulates colony-stimulating factor-1 production in placental
      villous core mesenchymal cells.
AB  - The human placenta is known to produce hematopoietic growth factors, including
      colony-stimulating factor-1 (CSF-1). We have previously demonstrated interleukin
      1 beta (IL-1 beta) production by decidualized endometrium during pregnancy. Since
      IL-1 stimulates CSF-1 production in fibroblasts, endothelial cells, and bone
      marrow stromal cells, our present study was designed to determine whether IL-1
      could also regulate CSF-1 production by placental villous core mesenchymal cells.
      Initial studies using enzymatic digestion separation of the trophoblast and
      villous core demonstrated that CSF-1 mRNA is mainly expressed in the placental
      villous core. Subsequently, long term monolayer cultures of villous core
      mesenchymal cells isolated from 9- to 16-week gestation placentas were
      established after enzymatic dissociation of intact placental villi to study the
      regulation of villous core cell CSF-1 production. The morphology of the cells and
      immunohistochemical staining for vimentin, cytokeratin, and CD45 antigen
      confirmed that cultured cells were more than 95% mesenchymal fibroblasts. Time
      course experiments demonstrated a maximal increase in CSF-1 mRNA expression of
      approximately 6.0-fold over baseline levels 3 h after IL-1 beta treatment (10
      ng/mL), whereas increased CSF-1 protein production was first detected in the
      culture medium 3 h after IL-1 beta treatment and rose progressively over 42
      hours. Villous core mesenchymal cells incubated with 0-10 ng/mL IL-1 beta
      demonstrated a specific dose-response relationship for CSF-1 mRNA expression and
      protein production, first seen at 0.10 ng/mL and maximal with 10 ng/mL IL-1 beta.
      These results demonstrate that production of CSF-1 by placental villous core
      mesenchymal cells can be stimulated by IL-1 beta in vitro and suggest that
      decidual IL-1 may regulate placental CSF-1 production in vivo.

PMID- 1381375
TI  - Immunohistochemical localization of 3 beta-hydroxy-5-ene-steroid
      dehydrogenase/delta 5----delta 4 isomerase in human placenta and fetal membranes
      throughout gestation.
AB  - The regulation of steroid production by the placenta and fetal membranes is
      important for both the maintenance of pregnancy and the timing of parturition. 3
      beta-Hydroxy-5-ene-steroid dehydrogenase/delta 5----delta 4-isomerase (3 beta
      HSD) catalyzes an obligatory step in the biosynthesis of steroid hormones. We
      have determined the localization of 3 beta HSD in the human placenta, fetal
      membranes, and umbilical cord throughout gestation by immunohistochemical
      analysis, using a polyclonal antibody raised in rabbits against a purified
      preparation of human placental 3 beta HSD. In placenta, immunoreactive (IR-) 3
      beta HSD was localized in the syncytiotrophoblast and intermediate trophoblast
      cells at both villous and extravillous sites, but not in cytotrophoblast cells
      from 6 weeks gestation to term. At 6-7 weeks gestation, IR-3 beta HSD was
      distributed in the cytoplasm of syncytiotrophoblast in about half of placental
      villi. By 12-14 weeks, the syncytiotrophoblast of all placental villi stained
      positively for 3 beta HSD. In the fetal membranes, strong IR-3 beta HSD staining
      was found in the trophoblast and reticular layers of chorion and in invasive
      trophoblast cells in decidua, and weakly in decidual stromal cells and amniotic
      epithelium. No IR-3 beta HSD was found in amnion on the placental plate, but in
      the umbilical cord, IR-3 beta HSD was present in the amniotic epithelium and also
      in fibroblast cells in Warton's jelly. These observations demonstrate that the
      localization of 3 beta HSD immunoreactivity and, therefore, the presumed sites of
      delta 5- to delta 4-steroid interconversion throughout gestation are principally
      the syncytiotrophoblast and intermediate trophoblast cells in placenta and the
      trophoblast cells in chorion and decidua in fetal membranes.

PMID- 1381376
TI  - Insulin-like growth factor system gene expression in the human kidney.
AB  - Insulin-like growth factors (IGFs) have significant effects on renal function and
      have been implicated in renal development and hypertrophy. In order to
      investigate the renal IGF system in the human, we have used in situ hybridization
      to map the patterns of gene expression for IGF-I, IGF-II, IGF binding proteins-1
      and -2 and both the type-I and type-II IGF receptors in the adult kidney. Since
      the rat is a model for the study of IGFs in renal physiology and pathophysiology,
      we compared patterns of IGF gene expression in the rat and human kidney. IGF-I
      messenger RNA (mRNA) is not detected in the human but is abundant in the rat
      kidney, while IGF-II is abundant in the human but not detected in the adult rat
      kidney. IGF-II mRNA is concentrated in renal vascular system, including afferent
      arterioles and the medullary interstitium. IGF-I and IGF binding protein-1 mRNAs
      are colocalized in the rat medullary thick ascending limbs of Henle's loops, but
      neither is detected in the human kidney. IGF binding protein-2 mRNA is
      concentrated in glomeruli in both species, but, whereas in the human it is
      expressed in the epithelium of the distal nephron and collecting ducts, in the
      rat it is localized in the medullary interstitium. The patterns for both type-I
      and type-II IGF receptor gene expression are identical in both species; however,
      type-I receptor, mRNA is distinctly more abundant than type-II. Both IGF receptor
      mRNAs are abundant in the renal tubular epithelium of the medulla and both are
      barely detectable in proximal tubules. Type I receptor mRNA alone is abundant in
      glomerular structures. These observations suggest that the autocrine/paracrine
      roles of IGFs are quite different in rat and human kidney. The conserved patterns
      of IGF receptor expression, however, suggests that the role of circulating IGFs
      in regulating renal function may be similar across the species.

PMID- 1381377
TI  - Insulin-like growth factor-I and follicle-stimulating hormone suppress insulin
      like growth factor binding protein-1 secretion by human granulosa-luteal cells.
AB  - Local regulation of insulin-like growth factor binding protein-1 (IGFBP-1)
      production in the human ovarian follicle was investigated using cultured human
      granulosa-luteal cells. Both insulin-like growth factor-I (IGF-I) and follicle
      stimulating hormone (FSH) exerted a dual effect on granulosa cells: while
      estradiol (E2) production was increased by both stimulants, the addition of
      either of the two hormones led to a reduction in IGFBP-1 secretion by more than
      50%. Inhibition of IGFBP-1 production in response to IGF-I was dose
      dependent,with the highest effect observed at 5 nM IGF-I. A significant
      correlation was found between the increase in E2 and inhibition of IGFBP-1
      secretion in response to IGF-I. These observations may suggest a novel mechanism,
      at the follicular level, by which FSH and IGF-I amplify the IGF-I effect in the
      ovarian follicular cells.

PMID- 1381378
TI  - Interactions between CD4+ T-cells and rat Schwann cells in vitro. 1. Antigen
      presentation by Lewis rat Schwann cells to P2-specific CD4+ T-cell lines.
AB  - Interactions between CD4+ P2-specific T-cell lines and Schwann cells were
      examined in vitro by scanning electron microscopy (SEM) and T-cell proliferation
      studies. CD4+ T-cell lines clustered around and attached to Schwann cells which
      expressed Major histocompatibility complex (MHC) class II molecules. Only those
      P2-specific T-cell lines capable of inducing experimental allergic neuritis (EAN)
      when injected into adult Lewis rats clustered around the Schwann cells. T-cell
      lines responsive to P2 but not able to induce EAN did not cluster around Schwann
      cells. The addition of exogenous P2 protein inhibited in a dose-dependent way
      clustering and proliferation of the P2-specific T-cell lines. Cytoplasmic P2 was
      detected in Schwann cells by immunofluorescent labelling and the results of
      proliferation assays in this study suggest that endogenous P2 protein was
      processed by the Schwann cells and presented to T-cell lines in association with
      MHC class II molecules. The clustering and proliferation of class II-restricted
      CD4+ P2-specific T-cell lines in the presence of Schwann cells provides evidence
      for a role for Schwann cells as facultative antigen presenting cells, processing
      and presenting 'self' endogenous antigen to CD4+ T-cell lines capable of inducing
      EAN.

PMID- 1381380
TI  - Interactions between CD4+ T-cells and rat Schwann cells in vitro. 2. Cytotoxic
      effects of P2-specific CD4+ T-cell lines on Lewis rat Schwann cells.
AB  - The cytotoxic effects of CD4+ P2-specific T-cell lines on Schwann cells were
      examined in vitro with 51Cr-release cytotoxicity assays. Only those P2-specific T
      cell lines capable of inducing EAN when injected back into adult Lewis rats were
      cytotoxic to the Schwann cells. The addition of exogenous P2 protein was not
      necessary for the cytotoxic effect. The monoclonal antibody (mAb) OX6 directed
      against Major histocompatibility complex (MHC) class II molecules blocked
      cytotoxicity, indicating an essential role for MHC class II molecules in this
      interaction between CD4+ T-cell lines and Schwann cells.

PMID- 1381379
TI  - Adoptive transfer of experimental allergic encephalomyelitis using serum-free,
      chemically defined in vitro culture conditions.
AB  - Enhanced adoptive transfer of experimental allergic encephalomyelitis (EAE) in
      rats requires in vitro culture of encephalitogen-sensitized donor spleen cells
      with either myelin basic protein or T-cell mitogen for 18-72 h prior to transfer
      to unimmunized recipients. The required in vitro culture period offers an
      opportunity to address in detail cellular and molecular immunoregulatory
      processes involved in the development of EAE. Conventional culture conditions
      using fetal bovine serum may impose analytical limitations due to the chemical
      complexity of the media. To permit better definition of the chemical events
      associated with the development of EAE, we report the successful adoptive
      transfer of EAE in Lewis rats using completely chemically defined, serum-free
      culture conditions.

PMID- 1381381
TI  - Experimental allergic encephalomyelitis in susceptible and resistant strains of
      mice after adoptive transfer of T cells activated by antibodies to the T cell
      receptor complex.
AB  - Lymphoid cells from normal and myelin basic protein (MBP)-immune PL/J, SJL/J and
      (SJL x PL)F1 hybrid mice were activated by in vitro culture with monoclonal
      antibodies specific for CD3 or specific T cell receptor (TCR) V beta chains.
      Lymphoid cells activated in this manner from MBP-immune animals did not readily
      transfer experimental acute encephalomyelitis (EAE) to naive syngeneic recipients
      in contrast to lymphoid cells from the same source cultured with concanavalin A
      (ConA) or myelin basic protein (MBP). However, recipients of anti-TCR antibody
      activated MBP-specific blasts showed accelerated onset and increased severity of
      EAE following immunization with MBP as compared to unmanipulated control animals.
      Anti-TCR activated cells incorporated [3H]-thymidine at a level comparable to
      ConA or antigen-stimulated cells and secreted interleukin (IL)-2 at comparable
      levels Anti-TCR activated blasts were greater than 90% positive for CD3 and
      alpha/beta TCR, 60% CD4+ and 30% CD8+. PL/J or (SJL x PL)F1 recipients of anti
      TCR-activated spleen cells from syngeneic normal mice also had more severe EAE
      than control mice following immunization with MBP. Non-responder C57BL/10SnJ mice
      could be converted to responders by infusion of anti-CD3 or anti-V beta 8
      monoclonal antibody-treated syngeneic spleen cells taken from normal syngeneic
      unimmunized mice.

PMID- 1381382
TI  - Direct demonstration of the infiltration of murine central nervous system by Pgp
      1/CD44high CD45RB(low) CD4+ T cells that induce experimental allergic
      encephalomyelitis.
AB  - In experimental allergic encephalomyelitis (EAE), autoimmune T cells infiltrate
      the central nervous system (CNS) and initiate demyelinating pathology. We have
      used flow cytometry to directly analyse the migration to the CNS of MBP-reactive
      CD4+ T cells labelled with a lipophilic fluorescent dye (PKH2), in SJL/J mice
      with passively transferred EAE. Labelled cells constituted about 45% of the CNS
      CD4+ population at the time of EAE onset. Almost all (greater than 90%) of the
      PKH2-labelled CD4+ T cells from EAE CNS were blasts and were alpha/beta T cell
      receptor (TCR)+, CD44(Pgp-1)high, and the majority were CD45RB(low). By contrast,
      most PKH2-labelled CD4+ T cells in lymph nodes, although CD44high, were
      CD45RBhigh cells. The cells that were transferred to induce EAE were essentially
      similar to antigen-primed lymph node cell populations, containing less than 15%
      CD44high cells, and most of them were CD45RBhigh. The CD44high CD45RB(low)
      phenotype is characteristic of memory/effector T cells that have been activated
      by antigen recognition. The difference in CD45RB expression between CNS and LN
      could therefore reflect differential exposure and/or response to antigen.
      Consistent with this, PKH2-labelled CD4+ cells isolated from the CNS were
      responsive to MBP in vitro, whereas PKH2+ CD4+ cells from lymph nodes showed
      almost undetectable responses. In control experiments in which ovalbumin (OVA)
      reactive T cells were transferred, a small number of fluorescent-labelled CD4+ T
      cells were also detected in CNS, but there were very few blasts, and these
      remained CD45RBhigh. These results argue for induction of the memory/effector
      phenotype of CD4+ T cells, and their selective retention in the CNS, as a
      consequence of antigen recognition.

PMID- 1381384
TI  - Two techniques for electron opaque staining of elastic fibres using tannic acid
      in fresh and formalin fixed tissue.
AB  - Two electron microscopic staining techniques, one using tannic acid
      glutaraldehyde as a fixative, and the other using tannic acid-uranyl acetate
      solution as a stain on ultra-thin sections of glutaraldehyde fixed material, were
      directly compared for elastic fibre staining on several human and animal tissues.
      Various concentrations of tannic acid were compared using both techniques. The
      two techniques were also compared on formalin fixed tissues. The use of tannic
      acid-uranyl acetate solution as a stain on processed tissue is by far the more
      consistent technique and achieves equally good results on glutaraldehyde or
      formalin fixed tissue. It is suggested that the use of the term tannic acid
      technique/method should be reserved for this particular method to achieve a
      meaningful interpretation of results in scientific papers.

PMID- 1381385
TI  - Cortical and striatal structure and connectivity are altered by neonatal
      hemidecortication in rats.
AB  - The cortical cytoarchitecture, cortical thickness, corticostriatal connections,
      cortical dendritic arborization, and striatal patch-matrix compartmentalization
      were compared in rats with neonatal (1 day of age) or adult hemidecortication.
      Neonatal hemidecortication produced few changes in cytoarchitecture of the
      remaining hemisphere and did not preclude the development of a patch-matrix
      compartmentalization in either striatum. There was a significant modification of
      contralateral cortical-striatal connections, however, as there were extensive
      crossed connections from layer II/III of the prefrontal cortex in the neonatal
      hemidecorticates, which contrasts with connections from layer V in the normal
      brain. Adult hemidecorticates had no crossed corticostriatal connections.
      Neonatal hemidecortication also led to an increase in cortical thickness relative
      to adult operates or controls and the neonatal hemidecorticates, and led to an
      increase in dendritic arborization in layer II/III pyramidal cells of the
      somatosensory and motor cortex but not in the visual or temporal cortex. The
      results suggest that the behavioral sparing of sensorimotor and some prefrontal
      functions after neonatal hemidecortication could be supported, in part, by the
      anatomical changes in the prefrontal and sensorimotor connectivity and dendritic
      arborization.

PMID- 1381386
TI  - Enhanced activation is the mechanism of negative cross-resistance to Chlorpyrifos
      in the Dicofol-IR strain of Tetranychus urticae (Acari: Tetranychidae).
AB  - The mechanism responsible for negative cross-resistance to chlorpyrifos was
      examined in isogenic dicofol susceptible (Orchard-12) and resistant (Dicofol-IR)
      two-spotted spider mites, Tetranychus urticae Koch. The acetylcholinesterase of
      both strains was equally sensitive to inhibition by chlorpyrifos oxon. However,
      the Dicofol-IR strain showed increased oxidative activation of chlorpyrifos to
      chlorpyrifos oxon relative to the Orchard-12 strain, suggesting this mechanism is
      responsible for the observed negative cross-resistance.

PMID- 1381383
TI  - Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers
      of tubular malfunction in "non-tubular" renal disease.
AB  - AIM: To determine whether urinary beta 2-glycoprotein-1 assays can provide
      improved discrimination between chronic renal diseases which are primarily of
      tubular or glomerular origin. METHODS: Urinary beta 2-glycoprotein-1, retinol
      binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D
      glucosa-minidase and albumin were measured in 51 patients with primary glomerular
      disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease,
      and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in
      52 patients and plasma creatinine in all 89. The findings were compared between
      the diagnostic groups and with previously published data relating to primary
      tubular disorders. RESULTS: All 31 patients with plasma creatinine greater than
      200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding
      protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D
      glucosaminidase; the quantities were generally similar to those found in
      comparable patients with primary tubular pathology. Among 58 with plasma
      creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1,
      retinol-binding protein, and alpha 1-microglobulin excretion were less common and
      much smaller, especially in those with obstructive nephropathy and polycystic
      disease. The ratios of the excretion of albumin to the other proteins provided
      the clearest discrimination between the patients with glomerular or tubular
      malfunction, but an area of overlap was present which embraced those with
      obstructive nephropathy and polycystic disease. CONCLUSIONS: Increased excretion
      of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of
      tubular reabsorption, or both, is common in all the forms of renal disease
      investigated, and both plasma creatinine and urinary albumin must be taken into
      account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein
      1 greater than 1000 are highly suggestive of primary glomerular disease and those
      less than 40 of primary tubular disease. Used in this way, beta 2-glycoprotein-1
      assays provide superior discrimination between glomerular and tubular malfunction
      when compared with retinol binding protein but the best discrimination is
      provided by albumin: alpha 1-microglobulin ratios.

PMID- 1381387
TI  - Effect of stilbene-type anion channel blockers on the immune response during
      experimental allergic neuritis (EAN).
AB  - We have studied the role of anion channel gating for the autoimmune response in
      experimental allergic neuritis (EAN) induced by bovine peripheral myelin (BPM).
      The influence of the stilbene-type anion channel blockers SITS and DIDS on T cell
      function was assessed by measurement of proliferation and by counting of
      interferon-gamma (IFN-gamma) secreting cells (IFN-gamma-sc) in response to BPM
      and phytohemagglutinin (PHA). SITS caused a dose-dependent increase of
      spontaneous proliferative activity as well as of proliferation in response to the
      antigenic stimulus BPM. In contrast, the drug caused a decrease of proliferation
      of cells stimulated with PHA. The number of cells induced to IFN-gamma secretion
      was reduced by SITS. The suppressive effect was dependent on the degree of
      activity of cells without drugs. Cultures showing high numbers of BPM reactive T
      cells were more easily suppressed than cultures with low numbers of BPM reactive
      T cells. Our results suggest that anion channel gating is involved in the
      triggering of T cells to IFN-gamma secretion. The anion channel signal pathway in
      lymphocytes could be a target for pharmacological intervention in inflammatory
      disorders. In the presently used autoimmune model, EAN, the net effect of in vivo
      treatment with SITS resulted in worsening of clinical signs and increased
      inflammatory cell infiltration in sciatic nerve, whereas the in vitro
      conductivity of sciatic nerve was not significantly affected by the drug. Thus
      anion channel gating seems to regulate activities of immune cells, and drugs with
      anion channel blocking properties may have effects that enhance autoimmune
      disease.

PMID- 1381388
TI  - Mechanism of peripheral T cell activation by coengagement of CD44 and CD2.
AB  - A number of CD44 antibodies are known to augment peripheral T cell proliferation
      stimulated with suboptimal concentrations of activating pairs of CD2 mAb. These
      findings have implicated the CD44 adhesion receptor in the activation of
      peripheral T cells via CD2. We have investigated early events after CD44 and CD2
      coengagement on peripheral T cells. CD44 and CD2 coengagement resulted in
      enhanced [Ca2+]i mobilization. However, the increase in [Ca2+]i mobilization did
      not occur until at least 3 min after CD2 and CD44 coengagement, suggesting that
      other events precede the elevation in [Ca2+]i. Using a T cell/fibroblast adhesion
      assay, we could demonstrate a dramatic increase in T cell adhesiveness after
      about 1 min after CD44 and CD2 coengagement. The increase in T cell adhesiveness
      was comparable to that induced by PMA. In the absence of antibodies or treatment
      with mAb directed to other T cell surface Ag, there was little if any adhesion
      between unstimulated peripheral T cells and fibroblasts. Enhancement of T cell
      adhesiveness through CD44 engagement was not mediated by a direct effect on
      lymphocyte-function associated Ag-3, the known ligand of CD2. However, cross
      linking of CD44 resulted in epitopic modulation of CD2 as demonstrated by the
      increased expression of the T11(3) activation epitope. Furthermore, anti-CD44
      could substitute for anti-T11(2) in the activation of peripheral T cells via CD2.
      These results suggest that CD44 ligation has profound effects on CD2-mediated
      events by inducing epitopic modulation of CD2.

PMID- 1381389
TI  - Identification of ezrin as an 81-kDa tyrosine-phosphorylated protein in T cells.
AB  - We have used APT affinity purification to isolate tyrosine-phosphorylated
      proteins from MRL lpr/lpr (lpr) mouse T cells. One such protein is pp81 ezrin,
      previously identified as a tyrosine-phosphorylated protein in epidermal growth
      factor-stimulated A431 carcinoma cells. Biochemical analyses in A431 and gastric
      parietal cells have revealed ezrin to be a cytoskeleton-associated cytosolic
      protein. In Jurkat T cells, however, using similar methods we have shown ezrin to
      be a cytosolic protein with no measurable cytoskeletal association. We also
      observed no increases in ezrin tyrosine phosphorylation in TCR-stimulated Jurkat
      T cells, unless the cells were pretreated with protein tyrosine phosphatase
      inhibitors, suggesting that T cell ezrin tyrosine phosphorylation is tightly
      controlled by protein tyrosine phosphatases. The fraction of tyrosine
      phosphorylated ezrin in lpr T cells was 5 to 10 times that observed in Jurkat T
      cells, which along with constitutive TCR-zeta phosphorylation and pp60fyn
      overexpression, is a feature of the lpr defect.

PMID- 1381390
TI  - Expression of murine beta 7, alpha 4, and beta 1 integrin genes by rodent mast
      cells.
AB  - The screening of a rat mast cell cDNA library with a probe selected to recognize
      those genes preferentially or exclusively expressed by mast cells identified a
      rat gene sequence, RF-17, that shared homology with the beta-integrins. This
      integrin was expressed in rat tissues enriched for mast cells and T cells. The
      rat RF-17 sequence was used to isolate the murine homologue from a spleen cDNA
      library. The murine gene encodes a protein of 806 amino acids that is the
      probable homologue to the human beta 7 chain. Transcripts specific for the murine
      gene are found in the thymus, spleen, and lung. To attempt to identify the gene
      product for this new integrin chain, we examined the murine T cell line TK-1,
      which expresses a novel integrin heterodimer, lymphocyte Peyer's patch high
      endothelial venule adhesion molecule (LPAM-1), of a known alpha 4 chain and an
      unknown beta P chain, for expression of murine beta 7 (RF-17). This cell line
      expresses high levels of RF-17 transcripts, suggesting that beta P is encoded by
      the beta 7 gene. Bone marrow cells induced to differentiate into mast cells via
      IL-3 express the beta 7 gene as well as the genes encoding the murine integrin
      alpha 4 and beta 1 proteins. Surface staining analysis indicates that these cells
      express an alpha 4-containing integrin complex throughout the differentiation
      process. These data suggest that the Peyer's patch homing LPAM-1 receptor
      expressed by a subset of T cells consists of the beta 7 gene product and the
      alpha 4 chain, and that this integrin chain complex is also found on the surface
      of maturing mast cells. The presence of beta 1 transcripts also suggests that
      these maturing mast cells possess the LPAM-2 integrin complex (alpha 4/beta 1) as
      well. The experimental strategy described in this manuscript has, thus,
      identified a novel murine beta-integrin chain that is expressed by rodent T cells
      and mast cells.

PMID- 1381391
TI  - Status of kappa L chain gene rearrangements and c-kit and IL-7 receptor
      expression in stromal cell-dependent pre-B cells.
AB  - Studies from several laboratories have provided evidence that distinct stromal
      cell-derived signals are involved in the maturation of pre-B cells into surface
      Ig expressing B lymphocytes. In order to define the stage of development at which
      these stimuli act, various polymerase chain reaction strategies were used to
      characterize the status of kappa L chain gene rearrangements in nontransformed,
      stromal cell dependent pre-B cells. These cells were obtained from lymphoid
      colonies whose growth was potentiated by factors from a stromal cell line. kappa
      L chain genes in cells from many of these colonies were rearranged, and analysis
      of the Jk genes used indicated a bias toward the most 3' loci. However, the use
      of a reverse transcriptase PCR strategy failed to detect mature kappa
      transcripts, indicating that stromal cell mediators exist that allow pre-B cells
      to progress to the stage at which L chain genes are rearranged but not expressed.
      Reverse transcriptase PCR further revealed that no transcripts for c-kit (the
      receptor for kit-ligand) and the IL-7R could be detected in these cells. This
      suggests that these receptors are no longer expressed by the time cells have
      undergone kappa rearrangements and minimize a role for stromal cell-derived kit
      ligand and IL-7 in mediating the pre-B to B cell transition.

PMID- 1381392
TI  - MHC molecules protect T cell epitopes against proteolytic destruction.
AB  - There is a subtle duality in the role of proteolytic enzymes in Ag processing.
      They are required to fragment protein Ag ingested by APC. However, prolonged
      exposure to proteolytic enzymes may lead to a complete degradation of the Ag,
      leaving nothing for the T cell system to recognize. What ensures that some of the
      Ag is salvaged? Using a cell-free system we demonstrate that an Ag fragment, once
      bound to a MHC class II molecule, is effectively protected against proteolytic
      destruction by cathepsin B and pronase E. The bound fragment, however, can be
      modified by aminopeptidase N. We suggest that MHC class II molecules play an
      important regulatory role in the physiologic processing of Ag.

PMID- 1381393
TI  - Complex of soluble human IL-6-receptor/IL-6 up-regulates expression of acute
      phase proteins.
AB  - IL-6 is a major regulator of acute phase protein synthesis in the liver. It
      exerts its action via a plasma membrane receptor consisting of two subunits, a
      ligand binding 80-kDa glycoprotein and a 130-kDa glycoprotein involved in signal
      transduction. We genetically generated a soluble form of the 80-kDa subunit of
      the human IL-6R (shIL-6R) in mouse fibroblasts (NIH/3T3 cells). The shIL-6R added
      to human hepatoma cells (HepG2) amplified the induction of alpha 1
      antichymotrypsin and haptoglobin by IL-6 at the mRNA and protein level. Moreover,
      a model for a liver permanently exposed to high IL-6 concentrations has been
      developed; HepG2 cells were stably transfected with human IL-6-cDNA; 10(6) of the
      transfected cells (HepG2-IL-6) synthesized and secreted 2 micrograms of IL-6
      within 24 h. Incubation of these cells with endogenous or exogenous IL-6 did not
      result in acute-phase protein induction. However, these IL-6-desensitized cells
      responded to other cytokines such as leukemia inhibitory factor, transforming
      growth factor beta 1, and IFN-gamma, known to modulate acute phase protein
      synthesis in the liver. Incubation of HepG2-IL-6 cells with shIL-6R reconstituted
      their responsiveness to IL-6 in a dose- and time-dependent manner. The possible
      biologic role that might be played by the shIL-6R in disease is discussed.

PMID- 1381394
TI  - Decay-accelerating factor expression on either effector or target cells inhibits
      cytotoxicity by human natural killer cells.
AB  - Previous studies have shown that freshly isolated CD16+ NK cells are deficient in
      the expression of decay-accelerating factor (DAF), or CD55, a membrane regulator
      of C3 activation. In this study we investigated the significance, for NK cell
      mediated lysis, of DAF expression on the target and effector cells. The effect of
      DAF expression on the susceptibility of NK cell targets was investigated by
      several means: first, DAF- cell lines were cloned from K562; second, the cloned
      DAF- cells were reconstituted with exogenous purified DAF; and third, anti-DAF
      F(ab')2 was used to block DAF function on the DAF+ K562 cells. Consistently, the
      presence of DAF in the target cell membrane, either naturally occurring or
      experimentally incorporated, afforded the target cell protection against lysis,
      and this protection could be blocked with anti-DAF. Similarly, targets for
      antibody-dependent cell-mediated cytotoxicity with exogenous DAF incorporated in
      their plasma membrane became less sensitive to antibody-dependent cell-mediated
      cytotoxicity by NK cells compared with the same target cells without incorporated
      DAF in their membranes. DAF incorporated in the plasma membranes of the effector
      NK cells made the NK cells less effective at killing K562 targets. The known
      function of DAF is to regulate C3 activation, and we were able to demonstrate
      that the isolated NK cell is capable of releasing C3. It is also possible that
      the participation of DAF in NK cell function represents a new, noncomplement
      dependent function for DAF.

PMID- 1381395
TI  - Cytotoxic activity and production of toxic nitrogen oxides by macrophages treated
      with IFN-gamma and monoclonal antibodies against the 73-kDa lipopolysaccharide
      receptor.
AB  - The hamster IgM mAb 5D3 is specific for an 73-kDa LPS receptor on murine
      leukocytes. This mAb inhibits binding of radiolabeled LPS to splenocytes and acts
      as an agonist for induction of LPS-mediated changes in macrophage function.
      Resident peritoneal macrophages treated with IFN-gamma and mAb 5D3 developed
      potent cytotoxic activity against tumor cells. Cells treated with IFN-gamma or
      mAb 5D3 alone were inactive. Macrophage cytotoxic activity induced by IFN-gamma
      and mAb 5D3 was inhibited by NGMMLA and coincident with high levels of NO2
      released into culture fluids. These data show that mAb 5D3 serves as an effective
      trigger signal for induction of cytotoxic activity with IFN-gamma-primed
      macrophages. Indeed, mAb 5D3 exactly mimicked the effects of LPS in these same
      systems. Unlike LPS, effects of mAb 5D3 on induction of macrophage cytotoxic
      activity and production of nitrogen oxides was abrogated after boiling, and not
      affected by addition of polymyxin B. The effects of LPS and mAb 5D3 as a trigger
      signal for IFN-gamma-primed macrophages were associated with production of TNF
      activity in culture fluids and inhibited by mAb against rTNF-alpha. Expression of
      class II MHC on macrophages induced by IFN-gamma treatment was suppressed by both
      LPS and mAb 5D3. These suppressive effects of LPS and mAb 5D3 were not affected
      by NGMMLA or mAb against rTNF-alpha. Finally, macrophages treated with LPS or mAb
      5D3 before exposure to IFN-gamma and LPS or mAb 5D3 did not develop cytotoxic
      activity or high levels of NO2- in the culture fluids. These same cells developed
      both effector activities after addition of rTNF-alpha. These results in toto
      identify the 73-kDa protein as a receptor that mediates LPS-induced changes in
      macrophage effector function. The mAb 5D3 serves as a specific and defined
      reagent agonist for analysis of LPS receptor-linked change.

PMID- 1381396
TI  - Identification of a new group-specific determinant on hepatitis B surface antigen
      with a synthetic peptide.
AB  - In a recent study we demonstrated that a synthetic peptide representing residues
      124-147 of the major protein of hepatitis B surface Ag (HBsAg) undergoes
      spontaneous oligomerization to reconstruct one or more conformational group
      specific determinants on HBsAg. The present study was undertaken to identify and
      characterize the HBsAg-related antigenic determinants on this oligomeric peptide
      (peptide OS[124-147]). A panel of nine analogs of this peptide was generated by
      either deleting, substituting, or chemical side chain modification of specific
      amino acid residues. With HBsAg subtype-specific antisera a single "a" epitope
      was identified as one that includes Met133 and Lys141. In addition a "d" epitope
      toward the amino-terminal end of the sequence was also observed. Perturbation of
      certain amino acid residues was found to enhance a antigenicity and subsequent
      experiments indicated that maximal expression of this a antigenicity is dependent
      in part on accessibility of the Lys141 side chain and in part on the primary
      sequence. With a total of 50 human anti-HBsAg serum samples obtained from
      individuals vaccinated against hepatitis B, it was demonstrated that these sera
      recognize the Met133-Lys141-dependent a epitope as the dominant, and in many
      cases the only, determinant on peptide OS[124-147]. Finally, on immunization,
      peptide OS[124-147] elicits an anti-HBsAg response that is predominantly anti-a
      though a lesser contribution from an anti-d response was also obtained.

PMID- 1381397
TI  - Expression of CD7 on normal human myeloid progenitors.
AB  - Existence of biphenotypic leukemias co-expressing CD7 and CD34 has prompted the
      question of whether a similar population of cells is present in normal human bone
      marrow. As CD7 is considered to be a T cell-restricted Ag, the co-expression of
      CD7 with the "human stem cell Ag" CD34 may identify a bipotent stage within
      hemopoietic differentiation. Cells with this phenotype have previously been
      isolated from human thymus. In this report we provide evidence that human marrow
      mononuclear cells also contain a minor subpopulation of cells co-expressing CD7
      and CD34. The CD7+/CD34+ cells were found to contain committed myeloid
      progenitors assayed both as CFU in semi-solid media and by their ability to
      produce granulocytes in long term marrow cultures. Expression of CD7 on myeloid
      committed progenitors was further confirmed in a C-mediated cytotoxic assay. We
      conclude that CD7 expression is not restricted to T cells but is also expressed
      during early stages of myeloid differentiation.

PMID- 1381399
TI  - Analysis of HIV-induced autoantibodies to cryptic epitopes on human CD4.
AB  - Antilymphocyte antibodies, including autoantibodies to CD4, have been reported in
      AIDS patients and are postulated to contribute to T cell depletion and
      immunologic dysfunction. In this paper, we characterize and localize binding
      sites of human anti-CD4 autoantibodies from a number of HIV+ patients. Epitope
      mapping by ELISA and Western blotting, together with cross-competition
      experiments, showed that common autoepitopes were localized to at least two
      topographically separate sites on the fourth domain of sCD4. These sites were
      partially dependent on the carboxyl terminus of the soluble molecule and were not
      exposed on full length membrane CD4, even under denaturing Western blotting
      conditions. Peptide screening identified peptides from the fourth and third
      domains that were recognized by several, but not all, anti-CD4 serum samples.
      Soluble CD4 affinity-purified antibodies were predominantly IgG1 and were not
      induced to bind mCD4 after gp120 binding to T cells. Analysis of HIV
      seroconversion panels showed that the appearance of anti-CD4 antibodies followed
      HIV seroconversion by 6 to 12 months and paralleled anti-gp120 reactivity. This
      suggested a correlation between immune reactivity to envelope and anti-CD4
      antibody production. Together, the data indicate that human anti-CD4 antibodies
      recognize cryptic conformational and linear epitopes on a cleaved form of CD4.
      These findings suggest that HIV may induce abnormal cleavage of full length CD4,
      thereby exposing immunogenic self epitopes normally hidden from humoral and
      cellular immune interactions. This model of abnormal processing of self Ag has
      general implications for autoantigen exposure in other autoimmune disorders.

PMID- 1381398
TI  - In vitro inhibitory effect of IL-8 and other chemoattractants on neutrophil
      endothelial adhesive interactions.
AB  - We have previously reported that cytokine- or LPS-activated human umbilical vein
      endothelial cell (HUVEC) monolayers secrete IL-8 that can act as a neutrophil
      selective adhesion inhibitor. In our study we investigated the mechanisms
      involved in the leukocyte adhesion inhibitory action of IL-8. The leukocyte
      adhesion inhibitory effect appears to be mediated by the action of IL-8 on the
      neutrophil, does not involve down-regulation of relevant endothelial adhesion
      molecules such as endothelial-leukocyte adhesion molecule-1 or intercellular
      adhesion molecule-1, and is quantitatively similar in different endothelial
      activation states that are predominantly endothelial-leukocyte adhesion molecule
      1 dependent or intercellular adhesion molecule-1 dependent. In addition to
      inhibiting the attachment of freshly isolated peripheral blood neutrophils to
      cytokine-activated HUVEC monolayers, IL-8 also promoted a rapid detachment of
      tightly adherent neutrophils from activated HUVEC, and abolished neutrophil
      transendothelial migration. Certain other chemoattractants, including FMLP and
      C5a, had similar inhibitory actions, indicating IL-8 was not unique in its
      ability to inhibit various neutrophil-endothelial interactions. In contrast, two
      other neutrophil agonists 1-0-alkyl-2-acetyl sn-glycero-3-phosphocholine and
      granulocyte-macrophage-CSF, which, like IL-8, are produced by activated HUVEC, as
      well as the leukocyte-derived chemoattractant leukotriene B4, exerted minimal
      inhibitory effects on adhesion. Regardless of their ability to modulate
      neutrophil-endothelial cell adhesion, all these agents induced altered leukocyte
      surface expression of functionally important adhesion molecules, including loss
      of L-selectin (leukocyte adhesion molecule-1, LECAM-1) and increase in
      CD11b/CD18. Thus, although the above agonists have been characterized primarily
      as chemoattractants, our findings demonstrate that these agents can exert a wide
      range of modulatory effects on neutrophil-endothelial adhesive interactions.

PMID- 1381401
TI  - Tolerance mechanism in experimental ovarian and gastric autoimmune diseases.
AB  - Neonatal splenocytes, neonatal thymocytes, or phenotypically mature adult
      thymocytes, transferred from normal BALB/c mice to syngeneic athymic nu/nu (or
      SCID) mice, led to autoimmune oophoritis and autoimmune gastritis, with
      corresponding serum autoantibodies, in the recipients. The overall disease
      incidence was 73%; the pathology ranged from mild to severe, with complete loss
      of ovarian follicles and gastric parietal cells. CD4+ neonatal spleen cells and
      CD4+ CD8- adult thymocytes were required for autoimmune disease induction. Adult
      spleen cells did not elicit disease, but they prevented disease when co
      transferred with neonatal spleen cells. However, in confirmation of an earlier
      report by Sakaguchi et al., (J. Exp. Med. 161:72, 1985), a subset of adult
      splenic T cells expressing a low level of CD5 molecules elicited similar
      autoimmune diseases. Thus, self-reactive T cells responsible for autoimmune
      disease of the stomach and ovary are not effectively deleted in the thymus, and
      they exist in the peripheral lymphoid organs of normal mice. We conclude that the
      functional expression of the self-reactive T cells is ontogenetically regulated;
      whereas T cells in the neonatal mice readily elicited autoimmune diseases in
      nu/nu recipients, regulatory cells may render self-reactive T cells in the normal
      adults unresponsive.

PMID- 1381400
TI  - Human decidual leukocytes from early pregnancy contain high numbers of gamma
      delta+ cells and show selective down-regulation of alloreactivity.
AB  - The mononuclear lymphoid cell population in human pregnant uterus mucosa,
      decidua, from early normal pregnancies was studied phenotypically and
      functionally. The phenotype was determined in situ by immunohistochemistry, and
      in isolated decidual mononuclear cell preparations by immunofluorescence and flow
      cytometry. A mild isolation procedure of gentle mechanical disruption followed by
      density gradient centrifugation was used. Leukocytes comprised a large part of
      the decidual tissue. They were present in aggregates mainly situated adjacent to
      the glandular epithelium. In addition, individual leukocytes were present
      intraepithelially, as well as scattered between the stromal cells and around
      vessels and lacunes. Four lymphocyte populations of approximately the same size
      were identified: TCR gamma delta+/CD56+ cells, TCR gamma delta+/CD56- cells, TCR
      gamma delta-/CD56+ cells, and TCR alpha beta+/CD8+ cells. TCR gamma delta-
      expressing cells comprised about 60% of the T cells. They were CD4-/CD8-, and
      about half of the TCR gamma delta+ cells expressed the memory/activation marker
      CD45RO. The Kp 43 Ag, earlier described on activated CD56+ and TCR gamma delta+
      cells in peripheral blood, was essentially only expressed on the TCR gamma delta
      /CD56+ cell population in decidua. At least 50% of the TCR alpha beta+ cells were
      CD8+. The function(s) of either one of these populations might be to prevent
      immunologic reactions against the fetus, to protect the uterus from unwanted
      extensive invasion of trophoblasts, or to protect the uteroplacental unit from
      infection. Decidual T cells did not respond to stimulation by alloantigens or
      mitogenic anti-CD3 mAb but responded to the same extent as PBMC to mitogenic
      lectins. The surface density of the TCR/CD3 complex was low on freshly isolated
      decidual lymphocytes, but could be up-regulated upon stimulation with
      PMA/Ionomycin. Local selective down-regulation of surface expression of the
      TCR/CD3 complex and of activation involving this complex might be one of the
      mechanisms by which a maternal immunologic reaction against the semiallogeneic
      fetus is prevented.

PMID- 1381402
TI  - Influence of free thiol group(s) on autoantibody-defined epitope of proliferating
      cell nuclear antigen.
AB  - Proliferating cell nuclear Ag (PCNA) is an intranuclear protein involved in DNA
      replication directed by DNA polymerase delta and is the target Ag of
      autoantibodies in some patients with SLE. There is evidence that the epitope on
      PCNA recognized by human autoantibodies is conformation-dependent and is not a
      continuous peptide sequence. Thimerosal, a mercury-containing sulfhydryl blocking
      compound, markedly reduced or abolished the reactivity of this autoantibody
      defined PCNA epitope. The thimerosal effect was observed in various Ag-detecting
      systems including indirect immunofluorescence, immunodiffusion,
      immunoprecipitation, and flow cytometry. The mechanism of the thimerosal effect
      appeared to be mediated through free but not readily accessible sulfhydryl group
      or groups. The sulfhydryl-modification by thimerosal could be reversed by
      competition with thiol-containing compounds. Experimentally induced mAb to PCNA
      generated by immunization with purified PCNA have been shown to recognize
      epitopes that are continuous peptide sequences and these epitopes were not
      affected by thimerosal. It has been shown that the human autoantibody-defined
      epitope is related to the function of PCNA because autoantibodies are able to
      inhibit DNA polymerase delta directed DNA replication, whereas experimentally
      induced antibodies are not. These studies show that certain sulfhydryl groups in
      PCNA have a role in determining the antigenicity of the epitope recognized by
      autoantibody and raise the possibility that certain sulfhydryl groups might also
      be associated with its function.

PMID- 1381403
TI  - Measuring cytokine levels in blood. Importance of anticoagulants, processing, and
      storage conditions.
AB  - The stability and recovery of six human recombinant cytokines (tumour necrosis
      factor (TNF), interferon-alpha (IFN-alpha), IFN-gamma, interleukin-1 alpha (IL-1
      alpha), IL-1 beta, and IL-6) from whole blood was investigated with a view to
      optimizing blood collection and storage procedures prior to performing
      immunoassays. Blood from healthy volunteers was subjected to various processing
      and storage procedures. Blood samples were treated with either: ethylenediamine
      tetraacetic acid (EDTA) (1.5 mg/ml blood) (E); EDTA/Trasylol (1.5 mg and 1000
      KIU/ml blood) (ET); heparin (30 IU/ml) (H) or allowed to clot (serum). The bloods
      were spiked with individual cytokines, split into aliquots and kept at 4 degrees
      C or RT. In the first instance spiked bloods from healthy volunteers (n = 5 per
      cytokine) were processed using sterile and non-pyrogenic materials and
      procedures. At regular time intervals, samples were cold spun, separated, flash
      frozen and assayed for the appropriate cytokine using RIA/IRMA methods. In a
      further study, timed separation was repeated with spiked blood from healthy
      volunteers (n = 5 per cytokine) using normal commercially available blood
      collection materials and procedures. In a third study, spiked blood from healthy
      volunteers (n = 3 per cytokine) was processed under sterile and non-pyrogenic
      conditions, and the blood samples separated, aliquoted and flash frozen within
      half hour of collection. These were then subjected to repeated cycles of freeze
      thawing at 4 degrees C or RT before assaying. In general, the stability of
      cytokines in whole blood was improved by storage at 4 degrees C and/or rapid
      separation. There was no significant difference between samples handled under
      sterile, non-pyrogenic conditions and those collected using normal blood
      collection procedures. The blood collection procedures described in this paper
      did not induce any of the six cytokines in the unspiked blood. Overall, EDTA
      treated samples performed most consistently. The addition of trasylol did not
      significantly affect the results. Most of the cytokines appeared unaffected by up
      to three freeze thaw cycles. The stability and recovery of the spiked cytokines
      varied from least stable to most stable spiked cytokine as follows; TNF-alpha
      less than IL-6 less than IFN-gamma less than IL-1 alpha less than IFN-alpha less
      than IL-1 beta. The recovery of spiked IFN-gamma from heparinized plasma samples
      was considerably higher than any other plasma or serum samples. The recovery of
      spiked TNF-alpha and IL-6 from serum samples was consistently lower than amounts
      recovered from plasma samples (anticoagulant treated).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1381404
TI  - A comparison of specific IgG antibody levels to the cell wall mannan of Candida
      albicans in normal individuals and in patients with primary antibody deficiency.
AB  - An enzyme-linked immunosorbent assay (ELISA) has been developed to measure
      specific IgG antibody to the polysaccharide, cell wall mannan of Candida albicans
      (mannan). The results were expressed as arbitrary units/ml, with an inter- and
      intra-assay coefficient of variation of 7-11%. In establishing normal ranges we
      found that specific IgG to the mannan increased with age, with 18% of healthy
      children aged 3-10, 48% of healthy children aged 11-19 and 76% of an adult donor
      population having specific IgG antibody to mannan (greater than 30 U/ml). We have
      compared these normal ranges, with a group of patients with primary antibody
      deficiency (PAD). None of the 23 patients with PAD, which included common
      variable immunodeficiency, IgG subclass deficiency, and selective IgA deficiency,
      had titres greater than 30 U/ml. The patients with PAD had significantly lower
      levels of specific IgG anti-mannan antibody (median 9 U/ml) compared to healthy
      children aged 11-19 (median 26 U/ml) or adults (median 58 U/ml) (p = less than
      0.001) but not children aged 3-10, (median 1 U/ml) (p = 0.08).

PMID- 1381405
TI  - A monoclonal antibody-based enzyme immunoassay for human GMP-140/P-selectin.
AB  - Two hybridoma cell lines producing monoclonal antibodies WGA-1 and PL7-6,
      reactive only with thrombin-stimulated human platelet have been established. Both
      these antibodies were investigated for their specific reactivity against GMP-140,
      based on the amino acid composition analysis of immunopurified antigen and N
      terminal amino acid sequencing of its protease fragments. A two-site enzyme
      immunoassay for quantification of human GMP-140 was developed using WGA-1
      monoclonal antibody immobilized on 96-well microplates and horseradish peroxidase
      labeled PL7-6 monoclonal antibody as detector. The assay was able to measure GMP
      140 in serum and plasma with a sensitivity of about 5 ng/ml and a precision
      better than 10%. This assay will be useful for the detection of GMP-140 derived
      from platelets or endothelium in biological fluids and tissue extracts.

PMID- 1381406
TI  - A monoclonal antibody recognising an epitope associated with pig interleukin-2
      receptors.
AB  - A monoclonal antibody is described which recognises an epitope associated with a
      receptor for interleukin-2 (IL-2) on pig lymphocytes. The monoclonal antibody
      inhibits high affinity binding of radiolabelled recombinant human IL-2 (rhIL-2)
      by pig lymphoblasts and also non-competitively inhibits both pig-TCGF and rhIL-2
      maintained proliferation. By flow cytometry the antigen is apparently not present
      on freshly isolated blood lymphocytes but is detectable on small cells between 6
      and 12 h after activation and on large cells by 24-h. These findings are
      comparable with those obtained using monoclonal antibodies recognising the 55 kDa
      alpha chain of the human and mouse IL-2 receptor (p55, TAC) expressed on
      activated cells in vivo and in vitro. However, the molecular weight of the
      porcine antigen is between 65 and 70 kDa.

PMID- 1381407
TI  - Galanin and the regulation of islet hormone secretion.

PMID- 1381408
TI  - P amylase is always greater than S in spot urine of normal subjects. Diagnostic
      implications.
AB  - Single random samples of urine were collected from 50 control subjects; 27
      patients with chronic pancreatitis; 19 with acute pancreatitis; 6 with acute on
      chronic pancreatitis; five in the recovery phase of acute attack; four patients
      with pseudocysts. Salivary (S) and pancreatic (P) amylase values were measured by
      cellulose acetate electrophoresis. The P amylase values always exceeded those of
      S amylase in the control specimens. In acute pancreatitis, both the lower and
      upper levels of total and P amylase were considerably higher than in the
      controls, and these high values tended to return to normal during the recovery
      phase of acute pancreatitis. The S amylase values were often very low or
      undetectable during the acute phase. Values for P amylase exceeded control values
      in patients with pseudocysts even in the presence of chronic pancreatitis. In
      chronic calcific pancreatitis, S amylase was higher than P amylase. We conclude
      that P amylase is always greater than S amylase in normal urine specimens, and a
      change in this pattern may be helpful in diagnosing various forms of
      pancreatitis.

PMID- 1381409
TI  - Chromatographic characterization of insulin-like growth factor-binding proteins
      in human pregnancy serum.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) in maternal and umbilical
      cord sera have been analysed by combinations of gel filtration chromatography,
      affinity cross-linking and electrophoresis. On gel filtration chromatography, the
      majority of circulating IGF-I in non-pregnant and pregnant women was present in
      the large molecular mass (150 kDa) binding proteins (IGFBP-3). In umbilical cord
      serum, by contrast, most IGF-I was present in the 40 kDa binding proteins
      (consisting of IGFBP-1 and IGFBP-2). Western blots demonstrated an apparent
      progressive attenuation of IGFBP-3 and IGFBP-2 in serum from pregnant women with
      an increase in IGFBP-1. After prior cross-linking with disuccinimidyl suberate,
      the 150 kDa fractions (IGFBP-3) from non-pregnant and pregnant serum showed a
      similar pattern on SDS-PAGE (several bands at different molecular masses).
      However, IGFBP-2 (one of the components of the 40 kDa fractions) was
      undetectable, even after cross-linking, in serum from pregnant women later than 8
      weeks of gestational age and in a mixture of maternal serum at term delivery and
      serum from non-pregnant women. This suggests that serum IGFBP-2 was degraded by
      specific proteases present in pregnancy serum. Following acid treatment, the 150
      kDa fractions from pregnancy serum were split into smaller subunits or fragments
      while the 40 kDa fractions remained unchanged, suggesting that the 40 kDa binding
      proteins, are acid-stable. The present data demonstrate that IGFBP-3 is the
      principal IGFBP in pregnancy serum even though there is an apparent reduction in
      serum IGFBP-3 activity as revealed on Western blots. The absence of IGFBP-2 in
      serum from pregnant women may be due to degradation by proteases. In the fetal
      circulation IGFBP-1 and IGFBP-2 appear to be the major binding proteins for IGF
      1.

PMID- 1381410
TI  - Motor unit function during evolution of proximal axonal swellings.
AB  - beta,beta'-Iminodipropionitrile (IDPN) impairs axonal transport of
      neurofilaments; their accumulation leads to the formation of proximal swellings
      in motor axons. Similar proximal swellings are a feature of some cases of motor
      neuron disease such as amyotrophic lateral sclerosis (ALS). Motor units in IDPN
      treated animals were assessed to determine their relative susceptibilities to
      impaired function and whether the functional changes resulting from proximal
      axonal swellings share certain electromyographic features with ALS. Intrinsic
      properties of medial gastrocnemius motoneurones (MN) and contractile responses of
      their motor units were examined during the evolution of proximal axonal swellings
      in cats administered IDPN (50 mg/kg once weekly) for 7, 14 or 35 days. While
      conduction velocities were significantly decreased in all motor unit types by 35
      days, the conduction slowing was greater in fast fatigable (types FF and FI)
      motor units than in fatigue resistant (types FR and S) motor units. Normal
      correlations between axonal conduction velocity and MN input resistance (Rin) and
      the inverse relationship between Rin and rheobase were lost with progression of
      the neuropathy. Twitch and maximum tetanic tension developed by fast-fatigable
      motor units declined early in the neuropathy, whereas fatigue-resistant units did
      not show similar changes until later stages of the intoxication. In some motor
      units, irregular and abnormal tetanic tensions were elicited by repetitive MN
      discharge. At 14 and 35 days, a novel, intermediate motor unit response
      classified as slow and fatigable (SF) was observed. Conduction block,
      characterized by repetitive MN firing without a corresponding contractile
      response, was observed in some type FF and S units by 35 days. Morphometric
      analysis of muscle fiber types showed significant atrophy, particularly in the
      type I fibers at 14-35 days; the atrophy reversed following cessation of IDPN
      administration. The influence of proximal axonal swellings on motor unit function
      in IDPN neuropathy is discussed in terms of reported electrophysiological
      alterations in motoneurone disease.

PMID- 1381411
TI  - Effect of treatment on oligoclonal IgG bands and intrathecal IgG synthesis in
      sequential cerebrospinal fluid and serum from patients with subacute sclerosing
      panencephalitis.
AB  - Oligoclonal IgG bands were analyzed in matching pairs of cerebrospinal fluid
      (CSF) and serum from 12 subacute sclerosing panencephalitis (SSPE) patients,
      using isoelectric focusing and immunofixation. Each patient was given
      isoprinosine, and four of the 12 patients were given alpha-interferon in
      addition. Two to 4 serial CSF and serum samples were collected from each SSPE
      patient during periods ranging from 1 to 16 months. In 3 SSPE patients a small
      number of new oligoclonal bands were seen in the follow-up CSF samples. In the
      other 9 SSPE patients there was no change in CSF band patterns between initial
      and follow-up specimens. Band patterns in serum remained unchanged between
      initial and follow-up samples. Although all 12 SSPE cases had higher IgG indices
      and increased rate of intra blood-brain barrier (BBB) IgG synthesis in comparison
      to patients with other neurological diseases, the values did not significantly
      differ between the first and follow-up specimens. We conclude that treatment of
      SSPE patients with isoprinosine or with isoprinosine and alpha-interferon had no
      significant effect on the CSF oligoclonal band profiles or IgG synthesis within
      the central nervous system.

PMID- 1381412
TI  - Optic neuritis anti-myelin basic protein synthetic peptide specificity.
AB  - Elevated titers of anti-myelin basic protein (anti-MBP) are highly associated
      with acute idiopathic unilateral optic neuritis as well as acute relapses of
      multiple sclerosis (MS). During acute phases of optic neuritis, free/bound
      antibody ratios are generally above unity, with high titers of free anti-MBP and
      relatively low or undetectable values of bound antibody. Three to 5 months after
      the acute phase when the majority of patients have recovered, free/bound anti-MBP
      ratios are below unity with low titers of free antibody and relatively higher
      levels of bound anti-MBP. Anti-MBP purified from cerebrospinal fluid of patients
      with optic neuritis are neutralized by synthetic peptides of human MBP containing
      overall amino acid residues 61-106 and do not react with synthetic peptides
      corresponding to residues 1-60 and 107-170. Anti-MBP may either have multiple
      epitopes in the region corresponding to residues 61-106 or it may react with a
      discontinuous epitope in this range. The mechanism of the optic nerve
      demyelination may be associated with anti-MBP binding in situ to MBP in the 61
      106 amino acid region.

PMID- 1381413
TI  - Vascular smooth muscle hyperplasia underlies the formation of glomeruloid
      vascular structures of glioblastoma multiforme.
AB  - The origin of the vascular hyperplasia seen in glioblastoma multiforme is a
      matter of debate. To test the predominant hypothesis that these glomeruloid
      structures are of endothelial origin the following study was undertaken. Seven
      glioblastomas containing prominent glomeruloid vascular structures were stained
      with Ulex europaeus agglutinin I (UEA-1) and with antibodies against factor
      VIII/related antigen (fVIII/RAg), glial fibrillary acidic protein (GFAP), S-100
      protein, muscle specific alpha-actin (MSA) and smooth muscle specific alpha-actin
      (SMSA). The GFAP and S-100 antibodies stained the neoplastic glial component of
      each tumor but did not bind to vascular cells. Endothelial cells lining the
      lumina of normal vessels and the lumina of glomeruloid vascular structures
      stained positively with both UEA-1 and fVIII/RAg antibody. No other cells were
      found to be stained by UEA-1 or by fVIII/RAg antibody. Smooth muscle cells of the
      normal vasculature stained positively exclusively with anti-MSA and anti-SMSA
      antibodies. The same pattern of positive actin antibody staining was seen in the
      majority of cells forming the glomeruloid structures; however, the cells lining
      the vascular lumina did not bind the MSA and SMSA antibodies. These data strongly
      suggest that the vascular proliferation resulting in glomeruloid structures is
      due in large measure to smooth muscle hyperplasia.

PMID- 1381414
TI  - Smooth muscle can comprise the sarcomatous component of gliosarcomas.
AB  - The sarcomatous component of gliosarcomas is thought by many to originate from
      the vascular proliferation seen in glioblastoma multiforme and has, therefore,
      been assumed to be endothelial. Immunohistochemical staining of four gliosarcomas
      has led us to an alternate theory. Pathologically all four tumors were composed
      of at least two cell types; the first had a stellate, glial appearance and the
      second was either spindled or polygonal in shape. Polygonal cells were associated
      with glomeruloid vascular structures in some areas. Both components of each
      neoplasm were cytologically malignant. Glial fibrillary acidic protein and S-100
      antibodies stained most of the glial-appearing cells and some of the spindled
      cells, but not the polygonal cells. Muscle specific alpha-actin and smooth muscle
      specific alpha-actin antibodies stained only the malignant spindled and polygonal
      cells and normal vascular smooth muscle. Ulex europaeus agglutinin I and anti
      factor VIII/related antigen antibody stained only cells lining vascular lumina.
      The staining results suggest that the malignant mesenchymal component of these
      tumors is of smooth muscle origin. Having demonstrated elsewhere that glomeruloid
      vascular structures of glioblastoma multiforme contain smooth muscle cells, we
      propose here that gliosarcomas can represent one end of the spectrum of glioma
      induced vascular smooth muscle proliferation.

PMID- 1381415
TI  - Progressive hind limb paralysis in mice carrying a v-Mos transgene.
AB  - To study the function of the protooncogene Mos in mouse brain development we have
      created a transgenic mouse model system in which an activated form of the gene,
      the murine retroviral v-Mos gene, is highly overexpressed in the brain. Six
      transgenic founder animals and mice of one established transgenic line (line
      TG66) displayed a progressive hind limb paralysis with onset between 18 days and
      9 months. The severity of the neurological phenotype correlated with pathological
      alterations and the degree of v-Mos expression in the brain which varied between
      individual animals of line TG66. The most striking feature of the brain pathology
      was the presence of large, abnormal astrocytes in the cerebellum, medulla,
      thalamus and in the dorsal horn of the spinal cord. These areas also contained
      shrunken and basophilic neurons whose cytoplasm was abnormally immunoreactive for
      phosphorylated epitopes of neurofilaments. In addition to neuropathologic
      changes, these mice also displayed aberrant eye lens differentiation and absence
      of hair cells in the inner ear. These results establish v-Mos transgenic mice as
      a model system to study progressive neurodegenerative disease and provide further
      evidence that the Mos protein-serine/threonine kinase has a function in brain
      development.

PMID- 1381416
TI  - Peripherin and neurofilament protein coexist in spinal spheroids of motor neuron
      disease.
AB  - We have compared the immunolocalization of neurofilament protein (NF) with two
      other neuronal-specific intermediate filament proteins in large spinal axonal
      swellings (spheroids) of motor neuron disease and controls. All spheroids labeled
      each of the three different subunits of NF, the low, middle, and high molecular
      weight polypeptides. In doublelabel immunofluorescence, 300 axonal swellings were
      immunostained for NF, and 87% of them contained the intermediate protein
      peripherin. The pattern of immunostaining of NF and peripherin was
      indistinguishable at a high resolution viewed in 1 microns optical sections by
      confocal microscopy. A minority of the spheroids contained alpha-internexin,
      another intermediate protein, but it was weakly immunoreactive. The
      immunostaining of axonal swellings was similar for all epitopes tested in motor
      neuron disease and control subjects. The findings suggest that peripherin as well
      as neurofilament protein are major components of the proliferated intermediate
      filaments in spheroids.

PMID- 1381417
TI  - Expression of mRNA for glial fibrillary acidic protein after experimental
      cerebral injury.
AB  - This study was undertaken to determine whether a mRNA for glial fibrillary acidic
      protein (GFAP) was present in increased amounts as a response to injury and, if
      so, how was its temporal expression related to the demonstration of GFAP by
      immunocytochemical techniques. A cerebral freeze-injury was produced in mice and
      at intervals thereafter the animals were anesthetized, perfused with formalin and
      histological sections of the brain through the injured area were prepared. A
      riboprobe for GFAP mRNA labeled with S35 and an immunocytochemical probe for GFAP
      were utilized to localize mRNA and GFAP immunoreactivity, respectively. For mRNA
      studies, the histological slide exposed to either sense or antisense probe was
      overlaid with x-ray film or dipped in photographic emulsion. The developed film
      was quantitated by digital image analysis. Emulsions were examined by dark-field
      microscopy. The results indicate that mRNA for GFAP is increased in the cortex in
      the environs of the injury by 6 hours, becomes maximal at 4-5 days, and is
      present in increased amounts up to 14 days. The message is enhanced in the
      adjacent cortex, the subpial region, the adjacent corpus callosum and in the
      ipsilateral and contralateral callosal radiations. This pattern of enhancement
      follows the distribution of post-injury edema. Glial fibrillary acidic protein is
      demonstrable at 24-48 hours after injury. Thus, there is a rapid response of the
      astrocyte to injury with increased mRNA expression that is followed by expression
      of GFAP immunoreactivity.

PMID- 1381418
TI  - Shunting of excitatory input to dentate gyrus granule cells by a depolarizing
      GABAA receptor-mediated postsynaptic conductance.
AB  - 1. Stimulation of the perforant path in the outer molecular layer of the adult
      rat dentate gyrus produced a depolarizing post-synaptic potential (DPSP) in
      granule cells when recorded using whole-cell techniques in the standard
      hippocampal slice preparation at 34 degrees C. The postsynaptic currents (PSCs)
      contributing to the DPSP were analyzed using specific receptor antagonists in
      current- and voltage-clamp recordings. 2. The DPSP reversal potential was
      dependent on the intracellular chloride concentration, and the amplitude of the
      DPSP was increased 55% after perfusion of the gamma-aminobutyric acid-A (GABAA)
      receptor antagonist bicuculline methiodide (BMI). The GABAA receptor-mediated PSC
      reversed at -66 mV, which was 19 mV positive to the resting membrane potential (
      85 mV) but hyperpolarized relative to action potential threshold. At -35 mV, the
      GABAA PSC had a latency to peak of 12.9 ms after the stimulus and decayed
      monoexponentially with an average time constant of 23.4 ms. 3. The component of
      the PSC blocked by the Quis/AMPA receptor antagonist 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX) had a latency to peak of 7.1 ms and decayed monoexponentially
      with a time constant of 9.9 ms at -35 mV. The N-methyl-D-aspartate (NMDA)
      receptor-mediated PSC, which was blocked by D-amino-5-phosphonovaleric acid (D
      AP5), had a waveform that was similar to the GABAA PSC: the latency to peak was
      16 ms and the decay was monoexponential with a time constant of 24.5 ms at -35
      mV. 4. The ratio of the peak PSCs mediated by GABAA, Quis/AMPA, and NMDA
      receptors measured at -35 mV with cesium gluconate electrode solutions was
      1:0.2:0.1. This ratio was essentially constant over the range of stimulus
      intensities that produced compound PSC amplitudes of 80-400 pA. 5. Measured at
      its reversal potential, the GABAA receptor-mediated postsynaptic conductance
      (GGABA-A) decreased the peak DPSP amplitude by 35%, shunted 50% of the charge
      transferred to the soma by the excitatory PSC, and completely inhibited the NMDA
      receptor-mediated component of the DPSP. 6. Simultaneous stimulation of
      presynaptic fibers from both the perforant path and interneurons results in a
      large depolarizing GGABA-A that inhibits the granule cell by shunting the
      excitatory PSCs. As predicted by models of shunting, the similar kinetics of the
      GABAA and NMDA PSCs leads to particularly effective inhibition of the NMDA PSC.
      The more rapid Quis/AMPA PSC is less affected by the GGABA-A, so that granule
      cell excitation under these conditions is primarily due to Quis/AMPA receptor
      activation.

PMID- 1381419
TI  - Modulation of excitatory amino acid responses in rat dorsal horn neurons by
      tachykinins.
AB  - 1. In freshly isolated spinal dorsal horn (DH) neurons (laminae I-III) of the
      young rat, the effects of tachykinins (substance P, neurokinin A) on inward
      current induced by excitatory amino acids were studied under whole-cell voltage
      clamp conditions. 2. When the cells were clamped to a holding potential of -60
      mV, a simultaneous application of N-methyl-D-aspartate (NMDA) (10(-4) M) and
      substance P (SP) (2 x 10(-9)-10(-7) M) for 10 s reversibly enhanced (by 129.6 +/-
      8.2%, mean +/- SE) the peak amplitude of the initial transient component of the
      NMDA-induced current in approximately 60% of the examined cells and reduced it
      (to 83.3 +/- 2.7%) in 27% of the cells. In addition, SP produced an increase (by
      133.6 +/- 11.7%) or a small decrease (to 85.9 +/- 1.4%) in the steady-state
      component of the NMDA response. In difference to SP, a simultaneous application
      of NMDA (10(-4) M) and neurokinin A (NKA) (10(-10)-10(-7) M) reversibly
      suppressed (to 86.8 +/- 2.1%) the peak amplitude of the NMDA-induced current in
      75% of the examined cells. 3. The NMDA-induced currents were modulated by
      tachykinins not only during the coadministration but up to 20 min after the
      removal of the peptide. SP potentiated the initial peak NMDA current by 147.9 +/-
      8.1% in 78% of examined cells and decreased it (76.3 +/- 5.7%) in 11% of cells.
      The potentiating effect was concentration-dependent (range: 10(-11)-10(-8) M) and
      reversible, but it was reduced with repeated applications. In addition, SP
      increased (by 125.4 +/- 3.6%) or reduced (to 86.0 +/- 1.8%) the steady-state
      component of the NMDA response. 4. When the single DH neurons were exposed to SP
      or NKA for 30 s-7 min before the testing of the NMDA responses, tachykinins had
      two distinct effects on the peak amplitude of the transient component of the NMDA
      induced current, consisting of an initial depression (SP: to 64.8 +/- 2.1%; NKA:
      to 76.3 +/- 4.4%) followed by a potentiation (SP: by 146.6 +/- 6.8%; NKA: by
      178.4 +/- 35.2%). The enhancing effect in some cells lasted less than or equal to
      1 h. 5. A claimed novel nonselective tachykinin antagonist, spantide II (10(-8)
      M) coadministered with NMDA (10(-4) M), slightly depressed the peak component of
      NMDA-induced current. In addition, it effectively blocked the SP-induced
      potentiation of the responses of DH neurons to NMDA.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1381420
TI  - Charybdotoxin and apamin sensitivity of the calcium-dependent repolarization and
      the afterhyperpolarization in neostriatal neurons.
AB  - 1. Intracellular recordings from neostriatal neurons in an in vitro slice
      preparation of the rat brain were used to analyze the pharmacological sensitivity
      of the action potential (AP) repolarization and the afterhyperpolarization (AHP)
      that follows a single action potential. The interspike voltage trajectory and the
      AHP could be divided into two main parts: a fast component lasting a few
      milliseconds and better observed during a train of spikes, and a slow component
      lasting approximately 250 ms and that comprises the main portion of the AHP. In
      some cells, a slow (up to 1 s) component of low amplitude was also detected. 2.
      Single APs were elicited at two imposed membrane potentials (around -60 and
      around -80 mV). The AP amplitude was larger, the repolarization rate was faster,
      and the duration was shorter when spikes were evoked at -80 mV. When measured
      from the -60 mV holding potential, the afterpotential was an AHP with peak
      amplitude of -5 mV. The afterpotential became a delayed depolarization (DD) at 
      80 mV. 3. Firing frequency adaptation was voltage sensitive. The firing of APs
      induced by long intracellular current pulses from a holding potential of -80 mV
      exhibited only a slow-frequency adaptation (time constant of seconds). However,
      at -60 mV, an initial and faster frequency adaptation was evident (time constant
      of tens of milliseconds). 4. The Ca2+ channel blocker Cd2+ retarded AP
      repolarization rate. This effect correlated with a significant block of the fast
      and slow components of the AHP. In contrast, Ni2+ had no significant effects on
      the same parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381421
TI  - NMDA receptor-mediated currents are prominent in the thalamocortical synaptic
      response before maturation of inhibition.
AB  - 1. The N-methyl-D-aspartate subtype of glutamate receptor (NMDAR) is thought to
      underlie synaptic plasticity in both adult and developing CNS; however, its
      involvement in the thalamocortical synapse has not yet been directly
      demonstrated. 2. Whole-cell, thalamus-evoked synaptic currents were recorded from
      layer IV cells in slices of immature mouse somatosensory cortex. 3. Earlier than
      postnatal day 9 the majority of responses were monosynaptic and purely
      excitatory, with both non-NMDAR and NMDAR-mediated glutamatergic components. 4.
      In older animals, disynaptic inhibitory currents summated with the excitatory
      ones and lowered the reversal potential of the response to voltages at which the
      NMDAR conductance is mostly blocked. 5. These findings suggest a cellular basis
      for the transient plasticity observed in layer IV during early postnatal
      development.

PMID- 1381422
TI  - Histamine activates chloride conductance in motor neurons of the lobster cardiac
      ganglion.
AB  - 1. Individual motor neurons of the lobster cardiac ganglion were voltage clamped
      with two microelectrodes. Superfusion of histamine evoked a concentration
      dependent membrane current. The mean effective concentration (EC50) for the
      concentration-effect relationship was 28 microM. 2. The amplitude and polarity of
      the histamine-activated current depended on intracellular and extracellular Cl-
      concentration. The membrane potential at which the current polarity reversed was
      a function of the Cl- equilibrium potential. 3. The histamine-activated Cl-
      conductance was voltage dependent, increasing with depolarization. As a
      consequence, the histamine-evoked current showed outward rectification. 4. We
      conclude that histamine activates a Cl- conductance with biophysical properties
      similar to the crustacean Cl- conductance activated by gamma-aminobutyric acid
      (GABA) and to the histamine responses described in lobster olfactory and
      stomatogastric neurons. 5. The response to histamine was competitively inhibited
      (IC50 = 7 microM) by cimetidine, an H2 subtype inhibitor in mammals. Ranitidine,
      pyrilamine, chlorpheniramine, diphenhydramine, and cyproheptadine were 50-100
      times less potent than cimetidine. Tubocurarine, a Cl- channel blocker, blocked
      with an IC50 of 20 microM, but picrotoxin did not begin to inhibit the histamine
      response until concentrations exceeded 0.1 mM. 6. These results suggest that the
      response cannot easily be classified with the use of the pharmacological
      categories developed in mammals. Like the Cl(-)-dependent responses to various
      neurotransmitters in a number of invertebrates, the histamine response in the
      lobster cardiac ganglion was inhibited by tubocurarine. 7. Both GABA and
      histamine had similar effects on the motor neurons, but only GABA inhibited
      pacemaker bursts. In this respect, GABA more resembles the endogenous inhibitory
      postsynaptic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381423
TI  - Cellular localisation of c-myc product in human colorectal epithelial neoplasia.
AB  - Aberrant expression of c-myc has been implicated in the development of colorectal
      carcinomas. We have used monoclonal antibodies 6E10 and 9E10, raised against mid
      sequence and C-terminal peptides of the c-myc protein, to study the distribution
      of myc protein in normal and diseased bowel at the light microscope and
      ultrastructural levels. Normal mucosa showed staining only of some nuclei in the
      proliferative zones of crypts. In adenomas, staining varied from predominantly
      nuclear to pancellular to focal or pancytoplasmic. Moderately well differentiated
      areas of carcinomas gave strong focal cytoplasmic staining, while in poorly
      differentiated tumours staining was pancytoplasmic. Electron microscopy with
      these antibodies detected myc protein associated with dense chromatin and, where
      cytoplasmic staining occurred, with polyribosomes. Tumours showed a reduced
      staining of nuclear pores compared with normal tissue. Comparison of staining
      patterns with 6E10 and 9E10 in normal tissue, adenomas, and tumours suggests that
      tumour progression is associated with an accumulation of cytoplasmic c-myc
      protein, perhaps resulting from alterations to the C-terminus which reduce the
      efficiency of nuclear targeting of the protein and thus disrupt the regulation of
      the cell cycle.

PMID- 1381424
TI  - P53 protein expression in lymphomas and reactive lymphoid tissue.
AB  - P53 is a tumour suppressor gene, located in the short arm of chromosome 17, which
      encodes for a nuclear protein involved in the control of cellular growth,
      regulating the entry of the cell into the S-phase. P53 mutations have been
      identified in a progressively increasing number of human malignancies. Nuclear
      p53 protein is usually present in non-tumour cells in minute concentrations, due
      to its short half-life. In contrast, tumours with p53 mRNA mutations show a
      higher nuclear protein concentration, detectable by immunohistological
      techniques, due to stabilization by complexing with other proteins such as heat
      shock protein or wild-type p53 protein. Levels of nuclear p53 protein detected by
      immunohistochemistry with the monoclonal antibody PAb 1801 were measured with the
      aid of an image analysis system in 83 non-Hodgkin's lymphomas (NHLs) and 13 cases
      of Hodgkin's disease, as well as in 14 cases of normal thymus, reactive tonsils,
      and lymphadenitis. High levels of p53 protein (greater than 5 per cent of the
      cells) were present only in high-grade lymphomas (in the proportion 13/55), with
      a peak incidence in Burkitt's lymphoma (5/8 cases). Lower levels (less than 5 per
      cent) of p53 protein were detected in low-grade B- and T-cell lymphomas, as well
      as in most of the cases of Hodgkin's disease, where p53 protein was selectively
      present in Hodgkin and Reed-Sternberg cells. In 5/14 reactive tonsils or lymph
      nodes, occasional p53-positive cells were identified. These results suggest a
      relationship between levels of p53 protein and the aggressiveness of
      NHL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381425
TI  - Lymphocytes in pseudomembranes of late prosthetic joint failure.
AB  - The pseudomembrane formed in association with late aseptic prosthesis failure
      contains a mixed giant cell and histiocytic infiltrate with variable numbers of
      lymphocytes. Immunolabelling with a panel of antibodies on paraffin sections was
      undertaken to define the nature of the lymphoid infiltrate in 19 cases. In all
      cases, the predominant lymphoid cell was a memory (CD45RO+, CD45RA-) T-cell. B
      cells were rare. Tissue from patients with rheumatoid arthritis (RA) contained
      greater numbers of T-cells when compared with patients with osteoarthritis (OA),
      suggesting that the intensity of the lymphoid infiltrates reflects the underlying
      joint disease rather than necessarily being part of a hypersensitivity response
      to wear debris.

PMID- 1381426
TI  - An immunohistological study of cartilage and synovium in primary synovial
      chondromatosis.
AB  - The antigenic phenotype of cartilage and synovial cells from six cases of primary
      synovial chondromatosis (PSC) was determined. This was compared with profiles
      similarly obtained for adult and fetal cartilage cells. The Ki-67 (proliferation
      associated) antigen was present on 40-50 per cent of chondrocytes in the
      proliferative zone of fetal epiphyseal cartilage but absent in chondrocytes of
      adult articular cartilage and PSC cartilage nodules. The absence of Ki-67 antigen
      suggests that there were no proliferating cells in the synovium or cartilage in
      these cases of PSC. In PSC alone, some chondrocytes in the cartilage nodules and
      mononuclear subintimal cells around the nodules also reacted for CD68, suggesting
      that growth of the cartilage nodules may occur by a metaplastic process. All
      synoviocytes in PSC were positive for leucocyte common antigen, HLA-DR, and CD68,
      a pattern typical of reactive rather than normal synovium.

PMID- 1381427
TI  - Tissue-type plasminogen activator and its inhibitor in human glomerulonephritis.
AB  - We carried out an immunohistochemical study of tissue-type plasminogen activator
      (PA) and urokinase-type PA, and their inhibitors, PA inhibitor-1 and PA inhibitor
      2, using renal biopsy specimens obtained from 86 patients with various forms of
      glomerulonephritis. The controls were four normal renal tissue specimens. On
      immunofluorescent observation, granular staining for tissue-type PA was found to
      be distributed along the glomerular capillary walls. The fluorescence was weak in
      the normal renal tissue and occasionally intense in the tissues of patients with
      IgA nephritis, minimal change nephrotic syndrome, and lupus nephritis. PA
      inhibitor-1 was abundant in the glomerular epithelial cells and scarce in the
      mesangial area and glomerular capillary lumens of the normal renal tissues. This
      was confirmed by immunoelectron microscopy using gold staining. The fluorescence
      of PA inhibitor-1 was weaker in some specimens of nephritic tissues than in the
      normal renal tissues. Urokinase-type PA and PA inhibitor-2 were negative within
      the glomeruli in all the specimens. In the glomerulonephritic tissues which were
      fibrin deposition-positive, tissue-type PA expression in the glomeruli tended to
      be strong. An association between fibrin deposition and PA inhibitor-1 staining
      was not clear. These data suggest that expression of tissue-type PA in the
      glomeruli increases in association with fibrin deposition.

PMID- 1381428
TI  - The search for the universal fixative or 'magic juice'.

PMID- 1381429
TI  - Immunolocalization of regenerating cells after submassive liver necrosis using
      PCNA staining.
AB  - Little data exist on the proliferative state of liver cells and its relationship
      with various morphological findings in acute liver failure (ALF) in man. In this
      study we used the monoclonal antibody NCL-PCNA (clone PC-10) against the
      proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin
      sections of 3 normal livers, 14 post-mortem needle-specimens of submassive
      hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy
      specimens obtained at transplantation in patients with acute or subacute liver
      failure of presumed viral aetiology. In normal livers, only occasional sinusoid
      lining cells were stained, whereas in SHN following POD or presumed viral
      hepatitis, hepatocytes of variable morphology showed significant
      immunoreactivity. Following POD, immunoreactivity was higher in samples taken
      within 5-6 days than in those obtained at 9-11 days, a pattern reminiscent of the
      decrease in the rate of regeneration, previously documented after partial
      hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar
      'nodules' in cases with a map-like distribution of collapsed and non-collapsed
      parenchyma. Ductules demonstrated comparatively less staining, but extensive
      labelling was exceptionally found in areas of complete hepatocellular dropout. In
      these areas, small elongated cells with strongly PCNA-positive ovoid nuclei,
      forming periportal sprouting cords or incorporated into the lining of ductules,
      were most remarkable in that they closely resembled 'oval cells' described in
      animal studies.

PMID- 1381430
TI  - The distribution of LH39 basement membrane epitope in the tumour stroma of oral
      squamous cell carcinomas.
AB  - LH39 monoclonal antibody detects a novel component of epithelial and endothelial
      basement membranes. The expression of LH39 antigen was investigated by
      immunohistochemistry in 55 oral squamous cell carcinomas and compared with 15
      pyogenic granulomas of skin and oral mucosa, 20 non-specific oral ulcers, and 20
      specimens of normal oral mucosa. The distribution of this basement membrane
      epitope was compared with that of other basement membrane components, type IV
      collagen, and laminin. LH39 monoclonal antibody labelled basement membrane
      surrounding small blood vessels in normal human organs. In oral squamous cell
      carcinomas, in contrast to the other basement membrane antigens, the LH39 epitope
      was not detectable in vessels within histologically recognizable tumour stroma.
      Neovascularization is known to attend malignant neoplasms and this finding was
      interpreted as absence of LH39 antigen within newly formed vessels. In support of
      this hypothesis, LH39 immunoreactivity was absent in newly formed blood vessels
      within pyogenic granulomas and the granulation tissue within ulcers. As
      increasing neovascularization is reported to correlate with a rising rate of
      metastasis, assessment of tumour angiogenesis may be of value in selecting
      patients for initial aggressive therapy.

PMID- 1381431
TI  - Assessment of p53 protein expression in normal, benign, and malignant oral
      mucosa.
AB  - Recent studies have shown the accumulation of high levels of p53 protein to be
      associated with malignant disease, within a range of tissues. This paper assesses
      p53 expression in oral mucosal disease. Biopsies were obtained from a range of
      oral disorders which included normal, benign, premalignant, and malignant oral
      tissue. In addition, oral smears were obtained from a limited number of patients
      with biopsy-proven oral cancer. Expression of the p53 protein was assessed using
      the polyclonal antibody CM1, together with a standard immunoperoxidase technique.
      A total of 37 oral cancers were assessed, of which 20 were found to express the
      p53 protein (54 per cent of cases). The p53 protein was not identified in normal,
      benign, or premalignant oral mucosa (54 cases). The identification of p53 within
      biopsies of oral mucosal lesions would appear to correlate with oral malignancy.

PMID- 1381432
TI  - Epstein-Barr virus latent membrane protein expression by Hodgkin and Reed
      Sternberg-like cells in acute infectious mononucleosis.
AB  - In the light of reports of latent membrane protein (LMP) expression by Hodgkin
      and Reed-Sternberg (HRS) cells, paraffin sections of tonsil (two cases), lymph
      nodes (eight cases; three cervical, one axillary, and four inguinal) and spleen
      (four cases) from 14 patients with acute infectious mononucleosis (IM) have been
      examined for the presence of HRS-like cells and immunostained with an antibody to
      LMP. Sections of the tonsils and one lymph node were also stained with a panel of
      antibodies which characterize HRS cells of Hodgkin's disease. The tonsils
      contained abundant HRS-like cells, mainly adjacent to the crypts, which were
      highlighted by strong LMP expression. The immunophenotype of these cells closely,
      but not completely, resembled that of HRS cells of Hodgkin's disease. The lymph
      nodes and spleens showed the typical changes of acute IM but only few LMP
      positive HRS-like cells were present in the cervical lymph nodes and hardly any
      were present in the inguinal nodes and spleen. These findings suggest that
      tonsillar crypt squamous epithelium may play a role in the formation of LMP
      positive HRS-like cells; these cells could be progenitors of Hodgkin's disease
      HRS cells and, if so, this might explain the restricted sites of presentation of
      Hodgkin's disease.

PMID- 1381434
TI  - Parathyroid glands in primary hyperparathyroidism: an ultrastructural
      morphometric study of 25 cases.
AB  - In parathyroid glands removed from patients with primary hyperparathyroidism
      (pHPT), hyperplasias and adenomas cannot be distinguished from one another by
      light microscopy when only one gland is available for examination. When a second
      gland is available, it is necessary to establish whether it is normal,
      suppressed, or hyperplastic. This distinction may be difficult, and the main
      criterion is the amount of cytoplasmic lipid in the parenchymal cells. If the
      lipid is abundant, the gland is considered normal or suppressed, and if it is
      scanty, the gland is interpreted as hyperplastic. We have performed a
      morphometric ultrastructural study to test the reliability of this criterion.
      Twenty-five adenomatous glands removed from patients with pHPT, when compared
      with glands of normal size from euparathyroid patients, showed a significant
      increase in the parameters indicative of metabolic activity, namely the size of
      the Golgi apparatus, the amount of rough endoplasmic reticulum, and the length of
      plasmalemmas. In addition, the amount of cytoplasmic lipid was significantly
      reduced. Furthermore, 25 glands of normal size removed from the same patients
      with pHPT showed an amount of lipid similar to that of normal glands from
      euparathyroid patients. However, all the parameters indicative of metabolic
      activity were significantly higher than those in glands from euparathyroid
      patients and comparable to those found in adenomatous glands. These results
      suggest that in pHPT, normal-size glands are as active as adenomatous glands,
      regardless of a higher lipid content.

PMID- 1381433
TI  - Mitochondrial and chromosomal DNA alterations in human chromophobe renal cell
      carcinomas.
AB  - Renal cell tumours are characterized by the loss of chromosome 3p and trisomy of
      5q segments (common, non-papillary renal cell carcinoma), or by trisomy of
      chromosomes 7 and 17 and loss of the Y chromosome (papillary renal cell
      carcinoma), or by random karyotype changes and mitochondrial DNA alterations
      (renal oncocytoma). We have studied by means of RFLP analysis the genomic and
      mitochondrial DNA in 11 chromophobe renal cell carcinomas, which have a unique
      morphology among kidney cancers. We found a loss of the constitutional
      heterozygosity at chromosomal regions 3p, 5q, 17p, and 17q, a combination of
      allelic losses that has not been found in other types of renal cell tumours.
      Three of the tumours showed a gross alteration in the restriction pattern of the
      mitochondrial DNA. A combined morphological and genetic analysis suggests that
      chromophobe renal cell carcinoma is a distinct entity.

PMID- 1381435
TI  - Flow cytometry of oesophageal mucosal biopsies; epidermal growth factor receptor,
      and CD15.
AB  - Flow cytometry may be used to examine the properties of single or isolated cells.
      We have shown that it is possible to disaggregate and label oesophageal
      epithelial cells for two surface markers, CD15 and epidermal growth factor
      receptor. We have previously demonstrated these markers in oesophageal squamous
      cells using immunoperoxidase techniques. These labelled disaggregated cells could
      then be measured by flow cytometry.

PMID- 1381436
TI  - Differential expression of integrin alpha chains by renal epithelial cells.
AB  - We have investigated the expression of integrin chains by human renal epithelial
      cells during in vivo renal differentiation and in vitro cell culture on different
      extracellular matrices. Using the immunoperoxidase technique to visualize the
      binding of monoclonal antibodies to different integrin chains in fetal and adult
      kidneys, we found a change during development from alpha 1 beta 1, alpha 3 beta
      1, and alpha 4 beta 1-positive blastemal cells to alpha 2 beta 1, alpha 3 beta 1,
      and alpha 6 beta 1-positive epithelial cells. The pattern of integrin expression
      correlates with the presence in the extracellular matrix of the appropriate
      ligands. In in vitro cell culture experiments, renal epithelium expressed alpha 3
      and alpha 5 integrins on all extracellular matrices. Integrins alpha 2 and alpha
      6 were found only in cells grown on a laminin-containing substratum. Fibronectin
      and alpha 5 integrin co-localized on the ventral surface of cells grown on a
      laminin substratum and at the periphery of cells on glass coverslips. These
      results suggest that there is a close relationship between integrin alpha chain
      usage and the presence of appropriate ligands in the extracellular matrix.

PMID- 1381437
TI  - Collagen composition and ultrastructure of the so-called amianthoid fibres in
      palisaded myofibroblastoma. Ultrastructural and immunohistochemical study.
AB  - A very prominent feature of the recently described intranodal palisaded
      myofibroblastoma is the occurrence of stellate crystalline extracellular deposits
      known as 'amianthoid fibres', and thought to represent abnormally thick collagen
      fibrils. We showed at the ultrastructural level that these deposits are composed
      of fibrils with the periodicity and width typical of normal native collagen.
      Using antibodies directed against various extracellular components, we have
      determined that these structures contain type I and III collagens. Our results
      indicate that the crystalloid deposits in intranodal palisaded myofibroblastoma
      called 'amianthoid fibres' do not contain giant collagen fibrils widely regarded
      as characteristic of the morphological concept 'amianthoid' in other locations.

PMID- 1381438
TI  - Characterization of HIV isolates arising after prolonged zidovudine therapy.
AB  - Human immunodeficiency virus type 1 (HIV-1) was isolated from five patients with
      late-stage disease treated with zidovudine (ZDV) for more than 1 year. Peripheral
      blood mononuclear cells (PBMCs) were used for all virus isolations and to assay
      for drug resistance. The isolates exhibited a 10- to 100-fold decrease in ZDV
      susceptibility compared to pretreatment isolates. Multiple clones of a 618 bp
      segment of the HIV reverse transcriptase gene encompassing codons 60-250 were
      sequenced for each isolate. The association of alterations at codons Asp67---
      Asn, Lys70----Arg, Thr215----Phe or Tyr, and Lys219----Gln with ZDV resistance
      has been previously noted (ref. 5). In this study, the most frequent alterations
      was Thr215----Tyr although genotypic mixtures of Thr/Tyr and Phe/Tyr were also
      observed. One isolate with a Tyr215 alteration and unaltered codons at 67, 70,
      and 219 had high-level ZDV resistance. Alterations at codons 67, 70, and 219 did
      not appear to increase resistance when seen in combination with Tyr215. Virus
      isolates obtained from each patient by cultivation with either 0 or 4 microM ZDV
      were compared and found to have similar alterations at codons 67, 70, 215, and
      219, although one instance of apparent in vitro selection for Tyr215 over Phe215
      was observed. Assays using PBMCs for virus propagation will permit susceptibility
      testing of HIV isolates from most patients on antiretroviral drugs to investigate
      the clinical significance of drug resistance.

PMID- 1381439
TI  - Concentrations of major plasma proteins in serum and whole-tissue extracts of
      porcine fetuses during development.
AB  - In extracts from fetuses up to 32 days of gestation, the major serum proteins
      were fetuin, alpha-fetoprotein and alpha 1-antitrypsin, but albumin was not
      detected. The concentration of all proteins rose with age until 40-50 days of
      gestation; and then the serum concentration of alpha-fetoprotein (2.9 mg ml-1),
      alpha 1-antitrypsin (4.4 mg ml-1) and transferrin (2.6 mg ml-1) fell
      progressively to about 1 mg ml-1 at birth, whereas those of fetuin, albumin and
      alpha 1-acid glycoprotein increased. The patterns of serum proteins in fetuses at
      about the middle of gestation were similar in extracts and sera. At birth, the
      major proteins were alpha 1-acid glycoprotein and fetuin, which accounted for 45
      and 18% of serum proteins, respectively. Albumin represented only 7% of serum
      proteins at this age. For most of the second gestational period, the six
      quantified proteins accounted for about 85% of total serum proteins. In early
      gestation, a significant proportion of serum proteins was intracellular.

PMID- 1381440
TI  - Viable embryos and normal calves after nuclear transfer into Hoechst stained
      enucleated demi-oocytes of cows.
AB  - Bovine oocytes were bisected, stained with Hoechst 33342 and observed under a
      fluorescent microscope to identify nucleated and enucleated demi-oocytes. Other
      oocytes were bisected but not stained, or bisected and only half of each oocyte
      stained, and viewed under a fluorescent microscope. The oocytes were then used
      for nuclear transfer by fusing them with embryonic blastomeres from a 5-6 day
      bovine embryo. The fusion rate and proportion developing into compact morulae or
      blastocysts was compared among different types of demi-oocytes. Expt 1 examined
      the effect of staining and indicated no effect on either fusion rate or embryonic
      development whether or not the oocytes were stained. In Expt 2, stained and
      unstained nucleated and enucleated oocytes were compared. As in the first
      experiment, there were no differences between stained and unstained demi-oocytes.
      There was no difference between fusion rates of nucleated and enucleated oocytes.
      However, there was a significant difference in embryonic development between
      nucleated (10.4%) and enucleated (22.6%) demi-oocytes (P less than 0.05). In a
      final experiment, stained and unstained enucleated oocytes were used for nuclear
      transfer and the resulting embryos transferred into recipient cows. There was no
      difference in pregnancy rates or in the number of normal calves born whether
      stained or unstained recipient oocytes were used. Results from these experiments
      indicate that Hoechst staining and fluorescent microscopy can be used to identify
      enucleated demi-oocytes, and that these can be used for nuclear transfer, and
      result in viable embryos and normal calves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381441
TI  - Motility characteristics and membrane integrity of cryopreserved human
      spermatozoa.
AB  - The motility characteristics of washed spermatozoa from 50 normal ejaculates were
      measured by time-lapse photography, before and after cryopreservation. Plasma
      membrane integrity was assessed by the hypo-osmotic swelling test and with the
      supravital fluorescent dye bisbenzimide (H33258). There was a marked decline in
      the percentage of progressively motile spermatozoa after cryopreservation, the
      extent varying widely among donors. Results were, however, consistent between
      different ejaculates from the same individual. The ability of spermatozoa to
      survive cryopreservation could not be predicted from the properties of the semen
      beforehand. The mean velocity of the spermatozoa was significantly reduced after
      freezing, but the lateral head displacement was unaltered. There was a
      significant reduction in the proportion of spermatozoa with intact plasma
      membranes after cryopreservation and the results of the hypo-osmotic swelling
      test and H33258 tests correlated closely. There was no correlation between the
      declines in the percentage of motile spermatozoa, or intact spermatozoa and the
      sperm velocity. We conclude that membrane rupture is not the sole cause of loss
      of motile spermatozoa during freezing and that the decrease in the proportion of
      motile spermatozoa is caused, at least in part, by a separate process from that
      responsible for the decrease in the average swimming speed of spermatozoa.

PMID- 1381442
TI  - Nine cystic fibrosis patients homozygous for the CFTR nonsense mutation R1162X
      have mild or moderate lung disease.
AB  - The clinical course of nine cystic fibrosis patients homozygous for the CF gene
      nonsense mutation R1162X was investigated. Since this mutation should lead to an
      interruption in the synthesis of the cystic fibrosis transmembrane regulator
      (CFTR) protein, a severe clinical course was expected. All patients showed
      pancreatic insufficiency, while the course of the lung disease was mild to
      moderate. These results suggest that this form of truncated CFTR protein, still
      containing the regulatory region, the first ATP binding domain, and both
      transmembrane domains, could be partially working in the lung tissues.

PMID- 1381443
TI  - Linkage of epidermolysis bullosa simplex to keratin gene loci.
AB  - Epidermolysis bullosa simplex (EBS) is an autosomal dominant disorder
      characterised by intraepidermal blistering of the skin. Two families with Weber
      Cockayne EBS have been analysed for linkage to keratin gene loci. In the first
      family, linkage was found to chromosome 17 markers flanking the keratin 14 gene
      (D17S74: Zmax = +2.45, theta = 0.10; COL1A1: Zmax = +0.97, theta = 0.00) and
      markers near the keratin 5 gene on chromosome 12 were excluded (D12S17: Z less
      than -2.0, theta = 0.08; COL2A1: Z less than -2.0, theta = 0.13). In contrast,
      the second family showed linkage to the region containing the keratin 5 gene
      (D12S17: Zmax = +1.37, theta = 0.08; COL2A1: Zmax = +0.33, theta = 0.15) and was
      not linked to the keratin 14 gene (D17S74: Z less than -2.0, theta = 0.14). The
      Weber-Cockayne form of EBS is genetically heterogeneous with linkage to different
      keratin gene loci.

PMID- 1381444
TI  - Structure of an isolated gramicidin A double helical species by high-resolution
      nuclear magnetic resonance.
AB  - A conformational species of gramicidin A has been isolated in dioxane by high
      pressure liquid chromatography and characterized by circular dichroism and two
      dimensional proton nuclear magnetic resonance. Double-quantum filtered two
      dimensional correlation spectroscopy, two-dimensional homonuclear Hartman Hahn
      spectroscopy and two-dimensional nuclear Overhauser effect spectra at 500 MHz
      were used to obtain virtually complete proton assignments and produce 192
      distance constraints. Protocols to determine the state of aggregation, monomer
      specific assignment of nuclear Overhauser enhancement values, hydrogen bonding
      pattern and helix handedness are described. A distance geometry/simulated
      annealing routine was used to generate well-defined backbone and side-chain
      structures. The species isolated is a right-handed intertwined double helix, with
      approximately 5.7 residues per turn. Unique values for helical dimensions are
      also specified.

PMID- 1381445
TI  - Crystal structure analysis, refinement and enzymatic reaction mechanism of N
      carbamoylsarcosine amidohydrolase from Arthrobacter sp. at 2.0 A resolution.
AB  - N-carbamoylsarcosine amidohydrolase from Arthrobacter sp., a tetramer of
      polypeptides with 264 amino acid residues each, has been crystallized and its
      structure solved and refined at 2.0 A resolution, to a crystallographic R-factor
      of 18.6%. The crystals employed in the analysis contain one tetramer of 116,000
      M(r) in the asymmetric unit. The structure determination proceeded by multiple
      isomorphous replacement, followed by solvent-flattening and density averaging
      about the local diads within the tetramer. In the final refined model, the root
      mean-square deviation from ideality is 0.01 A for bond distances and 2.7 degrees
      for bond angles. The asymmetric unit consists of 7853 protein atoms, 431 water
      molecules and four sulfate ions bound into the putative active site clefts in
      each subunit. One subunit contains a central six-stranded parallel beta-pleated
      sheet packed by helices on both sides. On one side, two helices face the solvent,
      while two of the helices on the other side are buried in the tight intersubunit
      contacts. The catalytic center of the enzyme, tentatively identified by inhibitor
      binding, is located at the interface between two subunits and involves residues
      from both. It is suggested that the nucleophilic group involved in hydrolysis of
      the substrate is the thiol group of Cys117 and a nucleophilic addition
      elimination mechanism is proposed.

PMID- 1381446
TI  - Mutations affecting RNA-DNA hybrid formation of the ColE1 replication primer RNA.
      Restoration of RNA I sensitivity to a copy-number mutant by second-site
      mutations.
AB  - Certain high copy-number mutants of the ColE1 plasmid produce a primer RNA that,
      unlike the wild-type, is resistant to inhibition by the plasmid-encoded
      replication inhibitor RNA I. We show that this resistance is associated with the
      ability of mutant primer RNA to hybridize to the DNA template strand more
      efficiently than does the wild-type transcript in vitro. We have isolated two
      second-site intramolecular suppressor mutations that partially restore wild-type
      copy number behavior to the high copy-number mutant in vivo. Each of these
      mutations alters a second base in primer RNA near the original mutation. We show
      that the primer RNA made by the pseudo-revertants regained wild-type-like
      sensitivity to RNA I in vitro. Also, the efficiency of RNA-DNA hybrid formation
      by the pseudo-revertant primer RNAs is restored to a level similar to that of
      wild-type primer. Using non-denaturing gel electrophoresis as an indication of
      RNA conformation, we identified two primer RNA conformers, each of 550
      nucleotides, whose equilibrium distribution differs between wild-type and the
      mutant plasmid. The pseudo-revertant plasmids have a conformer distribution
      similar to that of wild-type, indicating that these primer sequence changes have
      long-range effects on primer conformation. An oligonucleotide complementary to
      the primer domain containing the mutation reduced hybrid formation when present
      during primer elongation. These results indicate that the copy-number behavior of
      these plasmids is a consequence of conformational alterations in primer RNA that
      alter its hybridization efficiency with the DNA template strand and its
      sensitivity to inhibition by RNA I.

PMID- 1381447
TI  - Behavior of postcapillary venule pericytes during postnatal angiogenesis.
AB  - Autogeneic bone marrow was implanted into an artificially created cavity in a
      segment of rat sciatic nerve, after removal of nerve fascicles, without damaging
      the epineurium or surrounding microcirculation. Under these conditions, the bone
      marrow induces capillary growth and forms granulation tissue from surrounding
      tissues, the behavior of pericytes being studied in the preformed (preexisting)
      postcapillary venules of the latter. Beginning 20 h after bone marrow
      implantation, the pericytes of the preexisting postcapillary venules hypertrophy,
      with shortening of their processes, prominent nucleoli, dispersal of ribosomes
      into their free form, fragmentation of basal lamina, and increased DNA synthesis.
      The number of contact surfaces between pericytes and endothelium is noticeably
      lower than in controls. Many pericytes are in mitosis. Cells with a shape
      transitional between pericytes and interstitial fibroblast-like cells appear. In
      some cases, Monastral Blue (MB) was used as a marker of the cells in preexisting
      venule walls of the graft bed. In the earlier stages of the experiment, the MB
      labelling is restricted to the cytoplasm of pericytes and endothelial cells of
      postcapillary venules, and to the macrophages that occur in the space between
      pericytes and endothelium. Furthermore, the marker continues to be observed, at a
      later stage, in some of the following cells: pericytes and endothelial cells of
      the newly formed vessels, macrophages migrating into the interstitium,
      transitional cells between pericytes and fibroblasts, and typical fibroblasts of
      the granulation tissue. The present study provides greater evidence that
      preformed microvasculature pericytes are substantially activated during postnatal
      angiogenesis and granulation tissue formation, suggesting that they may
      contribute to the origin of new pericytes and fibroblasts.

PMID- 1381448
TI  - [Detection of minimal residual disease using reverse transcriptase polymerase
      chain reaction technique].
AB  - Polymerase chain reaction (PCR) is a highly sensitive technique to detect minimal
      residual disease (MRD) of hematological malignancy by amplifying tumor specific
      nucleotide sequences. When breakpoint is located over large lesions of genomic
      DNA, like t(9;22) leukemia, PCR amplifying cDNA of chimeric mRNA, called reverse
      transcriptase PCR (RT-PCR), can be utilized. We applied this method for the
      detection of MRD in patients with t(1; 19) acute lymphoblastic leukemia. RT-PCR
      detection of MRD in patients with leukemia might be useful for estimating of the
      depth of remission, for disclosing preclinical relapse, and for evaluating the
      efficacy of in vitro purging in autologous bone marrow transplantation.

PMID- 1381449
TI  - [Recent advances in the chemotherapy of leukemias].
AB  - Most recent progress in the treatment of leukemia and choice of therapies for
      obtaining "cure" from leukemia are discussed. Chemotherapy can now provide about
      40% long term survival in acute myeloblastic leukemia (AML) and about 20% disease
      free survival in acute lymphoblastic leukemia (ALL) of adults. Bone marrow
      transplantation (BMT) should be applied for the patients at risk in those
      leukemias (Cytogenetic abnormalities for AML and prognostic factors in ALL). In
      CML patients, BMT offers the only cure. Update result of interferon (IFN) therapy
      for CML is still a matter of controversy. Ex vivo treatment of autologous cells
      with IFN or drugs may be beneficial for CML patients without HLA identical donor.

PMID- 1381450
TI  - [Recent progress in the chemotherapy program and its theoretical background-
      malignant lymphoma].
AB  - Recently developed third generation chemotherapy programs have improved long-term
      disease free survival of patients with non-Hodgkin's lymphoma of aggressive
      histology, as compared with their predecessors. These protocols have been
      developed based on the cancer chemotherapy principles derived mainly of
      experimental tumor studies by H. Skipper and his group, and the theoretical
      approach by Goldie and Coldman to the occurrence of and chemotherapeutic
      overcoming of resistant clones. They are characterized by the use of multiple non
      cross-resistant drugs in maximally elevated dose intensity. Our third generation
      protocol, CAMBO-VIP, has produced 90% CR and 76% DFS at 3 years. Further
      improvement may be obtained by application of new drugs with different mechanism
      of action, effective means to destruct resistant cells, and further elevation of
      dose intensity by myelostimmulatory cytokines or transplantation of
      autologous/allogeneic peripheral blood or bone marrow stem cells.

PMID- 1381451
TI  - [Differentiation therapy of hematologic malignancies: principles, current status
      and perspectives].
AB  - There is increasing evidence that various tumor cells can be induced by
      differentiation inducers including biological response modifiers, synthetic
      chemicals and conventional anticancer drugs to differentiate terminally both in
      vitro and in vivo into cells with normal characteristics. The differentiated
      cells lose their abilities for proliferation and transplantation in animals.
      Furthermore, survival times of the animals inoculated with various tumors were
      found to prolong by administration with the differentiation inducers. These basic
      findings suggest that induction of terminal tumor cell differentiation is another
      strategy for cancer therapy: differentiation therapy of cancer. Principles,
      current status and perspectives of the differentiation therapy of leukemia are
      reviewed in this article.

PMID- 1381452
TI  - [High dose chemotherapy with autologous bone marrow transplantation and G-CSF for
      hematologic malignancies].
AB  - High dose chemotherapy (HDCT) followed by autologous bone marrow transplantation
      (ABMT) is one of the cure-oriented therapies for hematologic malignancies. Colony
      stimulating factors (CSFs) are currently used to stimulate hematopoiesis in
      various cytopenic conditions including post BMT. Granulocyte CSF (G-CSF)
      significantly accelerates granulocyte recovery after ABMT. Earlier recovery of
      neutrophils is associated with lower incidence of severe infections and shorter
      duration of reverse barrier nursing and hospitalization. Widespread use of G-CSF
      in ABMT may contribute to managing this treatment safely in multi-centers.
      Further prospective clinical study to define the optimal application and timing
      of HDCT with ABMT in hematologic malignancies is required.

PMID- 1381453
TI  - [Diagnostic value of measurement of RNA in platelets by fluorescence flow
      cytometry].
AB  - We analyzed the RNA in platelets by fluorescence flow cytometry after staining
      with thiazole orange(TO) in whole blood samples from hematologically normal
      subjects and patients with thrombocytopenia. The percentage of TO-positive
      platelets and their mean fluorescence channel number in 32 control subjects were
      6.2 +/- 2.5% (mean +/- SD) and 6.9 +/- 0.7, respectively. In 11 patients with
      idiopathic thrombocytopenic purpura, the percentage of fluorescently labeled
      platelets was significantly elevated (p less than 0.05) to 21.5 +/- 14.3%. By
      contrast, the proportion of positively stained platelets in 14 patients with
      thrombocytopenia due to impaired platelet production did not significantly differ
      from that of the controls, whereas the absolute counts of TO-positive platelets
      were significantly lowered (p less than 0.05). In both patient groups, the mean
      fluorescence channel numbers of TO-positive platelets were significantly elevated
      to 16.1 +/- 16.8 and 6.9 +/- 0.7, respectively (p less than 0.05, 0.005). We
      conclude that flow cytometric analysis of platelets after staining with TO
      provides information on the thrombopoietic activity in thrombocytopenic
      disorders. The main advantages of this method for clinical use are its simplicity
      and the rapidity.

PMID- 1381454
TI  - [Therapy of malignant liver tumors in childhood. An intermediate report of the HB
      89 multicenter study of the GPOH].
AB  - After a pilot phase in 1988 the liver tumour study HB-89 of the German Society of
      Pediatric Oncology and Hematology (GPOH) was started on January 1st 1989. It
      comprises the malignant epithelial liver tumours of childhood--hepatoblastoma and
      hepatocellular carcinoma. The objectives of the study are 1. to reduce surgical
      complications and incomplete tumour resections by restricting the primary
      operation to a lobectomy of the liver in case of small tumours or to a biopsy in
      case of extended disease, and 2. to reduce the size of large tumours by means of
      chemotherapy for subsequent resection. The tumourreductive and adjuvant
      chemotherapy consists of the combinations of ifosfamide, cisplatinum, adriamycin
      (IPA) and cisplatinum plus adriamycin as continuous infusion (PA-cont). Up to
      December 31st 1991 a total of 78 pediatric liver tumours were registered, 51 of
      those hepatoblastomas and 10 hepatocellular carcinomas. 19 (37%) hepatoblastomas
      were resected at primary operation (stage I and II). After chemotherapy 24 (83%)
      of 29 primarily inoperable hepatoblastomas (stage III and IV) became resectable,
      one child received a liver transplant. At the time all hepatoblastoma patients of
      stages I and II and 20 (69%) of stages III and IV are in remission, the overall
      remission rate is 81% (39/48). Seven patients with multifocal hepatoblastoma had
      an unfavourable outcome, only two are free of tumour. Of 10 patients with a
      hepatocellular carcinoma only three with a primary complete tumour resection are
      disease free. The IPA and PA-cont therapies were highly effective on
      hepatoblastomas (96%), but not on hepatocellular carcinomas.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1381456
TI  - Retention of progenitor cell function in CD34+ cells purified using a novel O
      sialoglycoprotease.
AB  - We previously showed that the sialoglycoprotein, CD34, which is expressed on
      primitive human hematopoietic progenitor cells, is cleaved by a unique
      glycoprotease from Pasteurella haemolytica (P.h. glycoprotease). This proteolytic
      enzyme specifically cleaves glycoproteins rich in O-sialoglycans. Glycoproteins
      containing only N-linked glycans are not cleaved. Cleavage of the CD34 antigen
      results in the loss of epitopes detected by five of seven CD34-designated
      antibodies. In this study, we investigated the role of the P.h. glycoprotease in
      isolating CD34+ cells from unfractionated normal human bone marrow mononuclear
      cells (MNCs), and determined the effect of the glycoprotease on the proliferative
      capacity of the progenitor-enriched fraction. CD34+ cells were isolated from MNCs
      using immunomagnetic beads attached via a CD34 antibody whose epitope is
      susceptible to removal by the cleavage with the glycoprotease. Subsequent
      cleavage with P.h. glycoprotease for 30 min at 37 degrees C released the CD34+
      cells from the beads with a recovery of up to 78%. Using a CD34 antibody whose
      epitope was not removed by the glycoprotease, up to 95% of the recovered cells
      expressed CD34. Compared to unseparated MNCs, the CD34+ cells showed the
      following enrichment of committed hematopoietic progenitors, as assayed in semi
      solid media: CFU-GM, 45-fold; CFU-M, 13-fold; BFU-E, 26-fold and CFU-GEMM, 81
      fold. Hematopoiesis was also studied in two-stage long-term bone marrow cultures
      in which the CD34+ cells were co-cultured over irradiated, allogeneic adherent
      layers. Output of CFU-GM over a seven week period from these cultures was similar
      to that from control cultures with autologous adherent-cell-depleted marrow MNCs.
      These data suggest that the loss of O-sialo-glycosylated peptide moieties from
      P.h. glycoprotease-released CD34+ cells neither affects the functional capacity
      of committed progenitors, nor impairs the proliferation of long-term culture
      generating cells. The P.h. glycoprotease can be used to facilitate the isolation
      and recovery of functionally competent CD34+ cells at high yield and purity,
      without prior removal of other adherent cells. The ability to rapidly purify
      CD34+ cells using this non-cytotoxic enzyme has important implications for bone
      marrow transplantation as well as for gene transfer studies in vitro.

PMID- 1381455
TI  - Value of retroperitoneal lymph node dissection in advanced testicular seminoma.
AB  - Seven patients with advanced seminoma of the testis (stages II C and III) were
      treated with 3 induction cycles of VAB-6 chemotherapy. Three patients had
      complete remission after chemotherapy and are alive disease free at 32, 38, and
      40 months with no additional treatment. Four patients were subjected to
      retroperitoneal lymph node dissection for residual retroperitoneal masses
      measuring 2-4 cm after chemotherapy, which revealed fibrosis in 2 patients and
      metastatic seminoma in the other 2. Patients with metastatic residual masses were
      given postoperative radiation therapy to the retroperitoneum and are alive
      disease free at 33 and 34 months, while those with fibrosis are alive disease
      free at 30 and 52 months, respectively, with no additional treatment.

PMID- 1381457
TI  - Effects of lorazepam tolerance and withdrawal on GABAA receptor operated chloride
      channels in mice selected for differences in ethanol withdrawal severity.
AB  - Withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) mice were
      treated with 5 mg/kg lorazepam for 7 days via implanted osmotic mini pumps.
      Following chronic drug treatment, brains were assayed for GABA-mediated chloride
      flux (GABA-Cl-). Under control (drug naive) conditions, brain membranes prepared
      from WSP and WSR lines did not differ in flunitrazepam or ethanol stimulation of
      GABA-mediated 36Cl- uptake, but the WSP lines were more sensitive to inhibition
      of 36Cl- flux by the inverse agonist, FG-7142. Membranes from lorazepam tolerant
      WSP and WSR mice were resistant to flunitrazepam- and ethanol-stimulation of GABA
      Cl-. Withdrawal from chronic treatment, by an acute injection with the
      benzodiazepine antagonist RO15-1788, returned flunitrazepam stimulation of GABA
      Cl- to near control levels in WSR membranes but not in WSP membranes and restored
      ethanol modulation of the channel to control levels in both lines. Inhibition of
      chloride flux by the benzodiazepine partial inverse agonist, FG-7142 was greater
      in membranes from WSP mice compared with WSR mice. Tolerance to lorazepam
      increased sensitivity of the WSR membranes to FG-7142 without altering the
      response in the WSP line. Again, withdrawal restored the Cl- flux response to FG
      7142 back to near control levels. Lorazepam tolerance lowered [3H]-flunitrazepam
      binding affinity slightly only in the WSR strain with no change in binding
      number. Withdrawal from chronic lorazepam treatment produced no significant
      change in binding affinity or number. The initial genotypic differences in
      benzodiazepine inverse agonist sensitivity, may be related to the selection for
      withdrawal seizure severity. Chronic administration of lorazepam reduces the
      coupling between the benzodiazepine agonist site and the chloride channel and
      concomitantly increases coupling between the channel and the inverse agonist
      site, while withdrawal resets the receptor coupling back to control response
      levels. However, for the WSP line, this drug environment dependent shift in
      channel coupling bias appears to be deficient compared with the WSR line.

PMID- 1381458
TI  - Mouse bone marrow micronucleus test using flow cytometry.
AB  - At present, the micronucleus test is the most popular short-term assay for the in
      vivo detection of clastogens or spindle poisons. As micronuclei are rare events,
      it has been argued that the conventional microscopical analysis based on 500-2000
      cells per animal does not provide enough sensitivity. In addition, the manual
      scoring of micronuclei is time-consuming and tedious. As an attempt to solve
      these problems, an automated method for the analysis of micronuclei in mouse bone
      marrow erythrocytes was developed using flow cytometry. Femoral bone marrow
      cells, from mice treated with known in vivo clastogens [mitomycin C (MMC): 0.5, 1
      or 2 mg/kg body weight intraperitoneally; benzene: 1000, 2000 or 4000 mg/kg body
      weight orally] or vehicles for the clastogens (physiological saline, olive oil;
      for control animals), were fixed with 1% glutaraldehyde, suspended in 70% ethanol
      for storing, stained with 4',6-diamidino-2-phenylindole (0.5 microgram/ml) and
      analyzed (50,000 cells per sample) in an EPICS V flow cytometer using a Coherent
      5W UV laser at 150-200 mV. The frequency of micronucleated erythrocytes (MNEs)
      was calculated from the cytometer, by a computer program involving model fitting
      to normal Gaussian distribution. Correlations between MNE frequencies obtained by
      manual microscopic observations (1000-2000 cells per animal) and by the flow
      cytometric measurements were good for both group results (means of 4-5 mice;
      linear correlation coefficient r = 0.89-0.998) and individual data (r = 0.82
      0.96). Repeated experiments with MMC showed good reproducibility for the flow
      cytometric scoring of micronuclei.

PMID- 1381459
TI  - Glutamine and macrophage function.
AB  - The effects of glutamine concentration on the phagocytosis of an opsonized
      antigen, the synthesis of RNA, and the production of interleukin-1 (IL-1) by
      macrophages were investigated in vitro. A minimum A minimum of 0.125 mmol/L
      glutamine was required for a significant increase in phagocytosis of opsonized
      sheep erythrocytes, compared with that recorded for macrophages cultured in the
      absence of glutamine. The synthesis of 3H-RNA by macrophages also required 0.125
      mmol/L glutamine in the culture medium before it was significantly increased
      above the levels of control cultures. A minimum of 0.03 mmol/L glutamine was
      required for the induction of significant levels of IL-1 by lipopolysaccharide
      (LPS)-stimulated macrophages. Therefore, recent findings suggesting that
      decreases in plasma glutamine resulting from major burn injury, sepsis, trauma,
      and surgery may be partly responsible for the associated impairment of immune
      function now have a basis in both phagocytosis and in modulation of the synthesis
      of IL-1 (the first cytokine of the interleukin cascade that leads to specific
      immunity) by macrophages, in addition to the previously established dependency of
      lymphocytes on external sources of glutamine for their replication.

PMID- 1381460
TI  - Transition metal complexes as probes of nucleic acids.

PMID- 1381461
TI  - Rapid screening for deletion mutations in the hprt gene using the polymerase
      chain reaction: X-ray and alpha-particle mutant spectra.
AB  - Conditions were devised for the isolation of DNA from single-mutant colonies on
      dishes, to give reproducible results in the polymerase chain reaction (PCR).
      Primers for 3 exons of the hamster hprt gene were used in a multiplex reaction to
      show rapidly whether the mutants carried deletions at these sites. 138
      independent mutants were screened in total, some spontaneous and others induced
      by X-rays or by alpha-particles from plutonium-238. Few deletions were found
      among the spontaneous set, while 'total' gene deletions formed about half the
      mutants found after irradiation. At equitoxic doses, little difference in mutant
      spectrum was found for the X-ray set compared to the alpha-particle set. This
      rapid technique should be applicable to many instances of comparative
      mutagenesis.

PMID- 1381462
TI  - Telomere association of human chromosomes induced by aphidicolin.
AB  - Telomere associations were studied in metaphase chromosomes from 96-h cultures of
      peripheral blood lymphocytes of two healthy women, treated with 0.4 microM
      aphidicolin for the last 72 h. Telomere associations were encountered in 2.9% and
      3.2% of the metaphases screened, whereas no such associations were encountered in
      5-fluorodeoxyuridine-treated cultures. The chromosome arms involved in telomere
      associations were nonrandom: 1q, 2q, 3q, 6p and 16q were more frequently involved
      in the associations (P less than 0.01). Of the 51 combinations of telomere
      associations encountered, those occurring nonrandomly were 1q/2q, 2q/2q, 4q/4q,
      6q/6q and 6p/6p associations.

PMID- 1381463
TI  - Effects of antioxidants on induction of micronuclei in rat peripheral blood
      reticulocytes by potassium bromate.
AB  - Micronucleus induction in male F344 rat peripheral blood by potassium bromate
      (KBrO3), a rat renal carcinogen, and its inhibition by several antioxidants were
      studied using the acridine orange supravital staining method. The frequency of
      micronucleated reticulocytes (MNRETs) peaked 32 h after a single i.p. treatment
      of rats with KBrO3 at a dose of 60 mg/kg. Co-treatment with glutathione (GSH) or
      cysteine (Cys) i.p. at doses of 800 mg/kg and 400 mg/kg, respectively, 30 min
      before and 30 min after the KBrO3 treatment significantly inhibited the
      micronucleus induction by KBrO3. Daily i.g. administration of vitamin C for 5
      days at a dose of 200 mg/kg/day was also effective in protecting against
      micronucleus induction by KBrO3 given on the 4th day. However, co-treatment with
      superoxide dismutase in liposome-encapsulated form by i.p. injection at a dose of
      18,000 U/kg 30 min before and 30 min after the KBrO3 application exerted no
      effect. The results indicate that antioxidants, especially sulfhydryl compounds,
      have protective potential against the clastogenicity of KBrO3, also suggesting
      that active oxygen species may play an important role in its clastogenicity.

PMID- 1381464
TI  - Persistence of chromosomal lesions induced in actively proliferating bone marrow
      cells of the mouse.
AB  - The persistence of chromosomal lesions induced in vivo by mitomycin C (MMC) was
      evaluated by cytogenetic analysis of mouse bone marrow cells. Chromosome
      aberration (CA) and micronucleus (MN) frequencies were estimated at different
      times after treatment, up to 42 days. The frequency of CA per cell decreased in
      the first 3 days after treatment, but a secondary peak appeared on the 4th day,
      followed by a stabilization around 0.03 CA per cell (significantly different from
      the control value), which persisted up to 17 days. At the next time intervals
      tested (28 and 42 days), the CA frequency returned to the control level. In
      disagreement with these data obtained directly on metaphases, the MN frequency,
      as evaluated in polychromatic erythrocytes, decreased quickly after treatment,
      reaching the control value on the 5th day. We attempted to enhance the
      sensitivity of the MN test by using CREST antibodies and indirect
      immunofluorescence. However, higher proportions of CREST- MN in treated than in
      control animals were observed only at short time intervals, confirming the
      results obtained with the conventional MN assay.

PMID- 1381465
TI  - Strand specificity for mutations induced by (+)-anti BPDE in the hprt gene in
      human T-lymphocytes.
AB  - Mutations in the hprt gene in T-lymphocyte clones isolated from primary cultures
      treated with the (+)-anti enantiomer of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-
      tetrahydrobenzo[a]pyrene (BPDE) in vitro, and from untreated control cultures,
      were characterized using polymerase chain reaction and direct sequencing of hprt
      cDNA and genomic fragments. The spectrum of BPDE-induced mutations was very
      specific and clearly different from the background spectrum, which comprised many
      different types of mutations. Of the BPDE-induced mutations, 20/22 were
      transversions of GC base pairs and 18/22 were GC greater than TA transversions,
      which is in agreement with what has been found in other mammalian systems. While
      no particular 'hotspot' was observed for BPDE in the hprt gene, a sequence
      context specificity was detected. Ten of the 14 BPDE-induced mutations in the
      coding region were located in the sequence context AGG, and 2 in AG
      dinucleotides, which indicates that such sequences are sensitive to BPDE
      mutagenesis. Nine of the 22 BPDE-induced mutations and 2/12 background point
      mutations caused mRNA splicing errors. Six of the BPDE-induced splicing errors
      were caused by GC greater than TA transversions in the AG dinucleotide of
      different splice acceptor sites, which indicates that these sites may be frequent
      targets of BPDE mutagenesis. All mutated GC base pairs in the BPDE-induced
      spectrum were oriented so that the guanine was located on the non-transcribed
      strand. Assuming that the premutagenic lesion in these cases was covalent binding
      of BPDE to guanine and that BPDE bound randomly to both strands, the strand
      specificity of the BPDE-induced mutations indicates that preferential excision
      repair of BPDE adducts on the transcribed strand occurs in the hprt gene in human
      T-cells.

PMID- 1381467
TI  - X-ray-induced specific-locus mutations in the ad-3 region of two-component
      heterokaryons of Neurospora crassa. XI. Heterozygous effects of gene/point
      mutations of genotype ad-3A or ad-3B.
AB  - Previous studies on X-ray-induced irreparable adenine-3 mutants (designated ad
      3IR), induced in heterokaryon 12 of Neurospora crassa, showed that they were not
      recessive, and that they demonstrated heterozygous effects in terms of markedly
      reduced linear growth rates as compared with a wild-type control (de Serres,
      1965, 1988). Homology tests on X-ray-induced irreparable mutants showed that they
      map, in the main part, as a series of overlapping multilocus deletions that
      extend both proximally and distally into the immediately adjacent genetic
      regions, as well as into the 'X' region (a region of unknown, but essential,
      function) between ad-3A and ad-3B (de Serres, 1969, 1989a). Studies on a larger
      sample of X-ray-induced multilocus deletion mutations of genotype (ad-3A)IR or
      (ad-3B)IR (de Serres et al., 1992) demonstrated that heterozygous effects are
      allele specific and that there was no correlation with genotype, radiation dose
      or complementation map position. Furthermore, the heterozygous effects of
      multilocus deletions in the ad-3 region can be modified genetically and
      biochemically (de Serres and Miller, 1988). In the present paper, the
      heterozygous effects of X-ray-induced gene/point mutations of genotype ad-3AR or
      ad-3BR, induced in heterokaryon 12 (Webber and de Serres, 1965; de Serres, 1988,
      1989a), were determined. The studies presented in this paper show that 8.1%
      (3/37) of X-ray-induced ad-3AR mutations exhibit heterozygous effects in terms of
      reduced linear growth rates in forced dikaryons with a gene/point mutant at the
      ad-3B locus, and 10.8% (4/37) in forced dikaryons with a multilocus deletion
      mutation covering the ad-3B locus. In addition, 24.3% (9/37) of ad-3AR mutations
      exhibit heterozygous effects in terms of enhanced linear growth rates in forced
      dikaryons with a gene/point mutant at the ad-3B locus. Similar studies with X-ray
      induced ad-3BR mutations showed that 54.9% (28/51) exhibit heterozygous effects
      in terms of reduced growth rates in forced dikaryons with a gene/point mutant at
      the ad-3A locus and 100.0% (48/48) in forced dikaryons with a multilocus deletion
      covering the ad-3A locus. These studies have also shown that about a 13-fold
      higher percentage of X-ray-induced multiple-locus mutations of genotype ad-3AR +
      RLCL have heterozygous effects resulting in reduced growth rates than X-ray
      induced single-locus mutations of genotype ad-3AR. The overall data base on X-ray
      induced ad-3 gene/point mutations in the present studies demonstrates that
      heterozygous effects are allele specific, genotype specific, and locus
      specific.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1381466
TI  - Forward mutations and DNA-protein crosslinks induced by ammonium metavanadate in
      cultured mammalian cells.
AB  - Ammonium metavanadate yielded a dose-dependent increase in mutation frequency at
      the V79 hprt locus following a 24-h exposure period in serum-free F12 medium.
      Vanadate also increased the mutation frequency of V79 cells by exposure of cells
      in salts-glucose medium, but these effects were not as striking, or as dose
      dependent as they were in serum-free F12 medium. Ammonium metavanadate enhanced
      the mutation frequency in a V79 variant containing a transfected bacterial gpt
      gene. These cells are known to be more responsive to oxidative type mutations,
      and to mutations involving deletions. Although the absolute level of mutations
      was greater in these cells with ammonium metavanadate, so was the background, and
      these cells did not exhibit an enhanced mutagenic response to vanadate when
      compared to the wild-type V79 cells. The vanadate results were compared to a
      positive control potassium chromate, which exhibited a dose-dependent increase in
      mutation frequency. Ammonium metavanadate induced DNA-protein crosslinks
      formation in both Chinese hamster ovary and human MOLT4 cells, and the role of
      these relatively unrepaired genetic lesions in the mutations produced by vanadate
      and chromate are discussed.

PMID- 1381468
TI  - Directly acting geno- and cytotoxic agents from a wild mushroom Dermocybe
      sanguinea.
AB  - The wild mushroom, Dermocybe sanguinea, contains several anthraquinone pigments,
      of which emodin (1,3,8-trihydroxy-6-methylanthraquinone) is quantitatively the
      most important. In our preliminary tests, Dermocybe sanguinea extracts were
      genotoxic without metabolic activation. The ethanol extract of Dermocybe
      sanguinea was fractionated by flash chromatography, and the emodin contents of
      the fractions were determined by HPLC. Their genotoxicities were assayed using a
      bacterial repair assay and sister-chromatid exchange analysis. The cytotoxicity
      of the fractions was assayed with mouse hepatoma cells using growth inhibition as
      the endpoint. The results of the biological tests were compared with those
      obtained with pure emodin. It was concluded that, in addition to emodin,
      Dermocybe sanguinea contains several other geno- and cytotoxic compounds.

PMID- 1381469
TI  - Lower birth weight of offspring born after self-poisoning of parent.
AB  - Birth weight was evaluated in 777 and 217 livebirths, respectively, of index
      females and female partners of index males born before and after severe self
      poisoning with drugs. Birth weight was also evaluated in matched controls. Babies
      born to index females months or years after an attempted self-poisoning were
      found to have a lower birth weight than before this suicide attempt. The
      difference in the birth weight of subsequent pregnancies of index and control
      females was also highly significant. A similar trend was observed in livebirths
      of female partners of index males. However, the differences were not significant
      between previous and subsequent pregnancies and between index cases and matched
      controls.

PMID- 1381470
TI  - Screening for mutations in human HPRT cDNA using the polymerase chain reaction
      (PCR) in combination with constant denaturant gel electrophoresis (CDGE).
AB  - Previously, we reported the modification of denaturing gradient gel
      electrophoresis called constant denaturant gel electrophoresis (CDGE). CDGE
      separates mutant fragments in specific melting domains. CDGE seems to be a useful
      tool in mutation detection. Since the hypoxanthine phosphoribosyltransferase
      (HPRT) gene is widely used as target locus for mutation studies in vitro and in
      vivo, we have examined the approach of analyzing human HPRT cDNA by polymerase
      chain reaction (PCR) and CDGE. All nine HPRT exons are included in a 716-bp cDNA
      fragment obtained by PCR using HPRT cDNA as template. When the full-length cDNA
      fragment was examined by CDGE, it was possible to detect mutations only in the
      last part of exon 8 and exon 9. However, digestion of the cDNA fragment with the
      restriction enzyme AvaI prior to CDGE enabled us to detect point mutations in
      most of exon 2, the beginning of exon 3, the last part of exon 8 and exon 9. With
      the use of two internal primer sets, including a GC-rich clamp on one of the
      primers in each pair, a region containing most of exon 3 through exon 6 was
      amplified and we were able to resolve fragments with point mutations in this
      region from wild-type DNA. The approach described here allows for rapid screening
      of point mutations in about two thirds of the human HPRT cDNA sequence. In a test
      of this approach, we were able to resolve 12 of 13 known mutants. The mutant
      panel included one single-base deletion, one two-base deletion and 11 single-base
      substitutions.

PMID- 1381471
TI  - Allelic losses in mutations at the aprt locus of human lymphoblastoid cells.
AB  - We analyzed the nature of mutations at the autosomal locus coding for adenine
      phosphoribosyltransferase (aprt) in human cells to elucidate the process(es)
      governing mutagenesis at autosomal loci. A human lymphoblastoid cell line, WR10,
      was found to be heterozygous for mutated allele at the aprt locus, and was used
      for mutation analyses. By the use of a restriction fragment length polymorphism
      associated with the aprt locus in WR10 cells, the molecular characteristics of
      mutations arising spontaneously or induced by gamma-rays were investigated.
      Eighty-five percent (22/26) of the spontaneous mutant clones and 93% (64/69) of
      the gamma-ray-induced mutant clones resulted from loss of one of the two aprt
      alleles. Determination of the dosage of aprt genes in those mutants with allelic
      losses revealed that approximately half of them retained two copies of the
      mutated allele. These data suggest that the mutational events leading to APRT
      deficiency are analogous to those reported for tumor suppressor genes in
      malignancies.

PMID- 1381472
TI  - Visible mutations induced by P-M hybrid dysgenesis in Drosophila melanogaster
      result predominantly from P element insertions.
AB  - This study supplied no evidence that P-M hybrid dysgenesis is a general release
      mechanisms for transposon movement. Newly induced mutations (23 singed, three
      yellow, and one white) were generated by hybrid dysgenesis and were molecularly
      analyzed for the presence or absence of P element insertions. Only one
      dysgenically-induced insertion mutation out of 27 analyzed was the result of a
      non-P insert; this frequency is not statistically above the non-dysgenic control
      level. Thus, it appears that individual transposable elements families are
      independently regulated.

PMID- 1381473
TI  - Comparative toxicity and mutagenicity of N-hydroxy-2-acetylaminofluorene and 7
      acetyl-N-hydroxy-2-acetylaminofluorene in human lymphoblasts.
AB  - Exponentially growing TK6 human lymphoblasts were exposed to either 0-50 microM N
      hydroxy-2-acetylaminofluorene (N-OH-AAF) or 0-10 microM 7-acetyl-N-hydroxy-2
      acetylaminofluorene (7-acetyl-N-OH-AAF) in both the absence and presence of a
      partially purified preparation of hamster-liver N-arylhydroxamic acid N,O
      acyltransferase (AHAT). Neither N-arylhydroxamic acid was toxic to the
      lymphoblasts, nor mutagenic at the thymidine kinase (tk) locus, in the absence of
      AHAT over the concentration range examined. In the presence of AHAT, an enzyme
      that activates N-arylhydroxamic acids to electrophilic N-acetoxyarylamine
      intermediates, both compounds caused toxicity and mutagenicity in TK6 cells. The
      7-acetyl-N-OH-AAF was approximately 10-fold more toxic and mutagenic than the
      unsubstituted N-OH-AAF. These data demonstrate that metabolism of these N
      arylhydroxamic acids, presumably to N-acetoxyarylamine intermediates by AHAT, is
      a key event in the biological activity of these agents. In addition, the presence
      of electron-withdrawing 7-acetyl substituent that is thought to stabilize N
      acetoxy intermediates, appears to enhance the biological activity of the
      unsubstituted N-OH-AAF.

PMID- 1381474
TI  - Enhancing effects of heterocyclic amines and beta-carbolines on the induction of
      chromosome aberrations in cultured mammalian cells.
AB  - The effects of post-treatment with heterocyclic amines and beta-carbolines on the
      induction of chromosome aberrations were studied in Chinese hamster CHO K-1 cells
      and SV40-transformed excision repair-deficient human XP2OSSV cells. The number of
      chromosome aberrations induced by UV and MMC were increased by post-treatment
      with Trp-P-1 and Trp-P-2, in both the presence and the absence of S9 mix. A alpha
      C, MeA alpha C, Glu-P-1, Glu-P-2, IQ, MeIQ, harman and harmine increased
      chromosome aberrations only in the presence of S9 mix. Glu-P-2, IQ, MeIQ, harman,
      and harmine did not induce chromosome aberrations by themselves at the
      concentrations used in this study. Trp-P-1, Trp-P-2, A alpha C, MeA alpha C and
      Glu-P-1 were weak clastogens by themselves, but at much higher concentrations
      than those at which they increased the induction of chromosome aberrations in
      cells pretreated with UV or MMC. Therefore, the increases in chromosome
      aberrations were not considered to be additive.

PMID- 1381475
TI  - Structure-activity relationships of aromatic diamines in the Ames Salmonella
      typhimurium assay. Part II.
AB  - Structure-activity relationships in the case of aromatic monoamines, diversely
      substituted on the ring, using the mutagenic activity in the Ames test were
      studied in part I. This part II is based on the same general principles but
      applied to phenylene diamines (ortho, para and meta) diversely substituted on the
      ring.

PMID- 1381476
TI  - Toxicological significance of dog liver cytochrome P-450: examination with the
      enzyme expressed in Saccharomyces cerevisiae using recombinant expression
      plasmid.
AB  - A complementary DNA (cDNA) coding for a form of beagle dog cytochrome P-450
      (Dah1), which is the orthologue to the CYP1A1 cDNA of rat, mouse and human, was
      inserted between the alcohol dehydrogenase (ADH) promoter and terminator regions
      of the yeast expression vector pAAH5. On introduction of the resulting
      recombinant plasmid pDC-1, Saccharomyces cerevisiae strain AH22 cells synthesized
      up to 1.5 x 10(5) molecules per cell of cytochrome P-450 protein (P-450(Dah1)).
      The carbon monoxide-bound reduced form of P-450(Dah1) showed an absorption peak
      at 447 nm and specific content of P-450(Dah1) was about 0.1 nmole P-450 per mg of
      microsomal protein. P-450(Dah1) cross-reacted with antibodies to rat P-448-H
      (CYP1A2) and dog P-450-D2 (CYP1A2). P-450(Dah1) activated 2-amino-3-methyl
      imidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline
      (MeIQ) most efficiently in the umu test and exhibited a high activity of aryl
      hydrocarbon hydroxylase toward benzo[a]pyrene.

PMID- 1381477
TI  - Monitoring and assessment of mercury pollution in the vicinity of a chloralkali
      plant. III. Concentration and genotoxicity of mercury in the industrial effluent
      and contaminated water of Rushikulya estuary, India.
AB  - Aquatic mercury pollution of the Rushikulya estuary in the vicinity of the
      chloralkali plant at Ganjam, India was monitored over a period from October 1987
      to May 1989. The concentrations of aquatic mercury in the water samples taken
      from the effluent channel and from different sites along the course of the
      estuary covering a distance of 2 km were periodically recorded and ranged from 0
      to 0.5 mg/l. The bioconcentration and genotoxicity of aquatic mercury in the
      samples were assessed by the Allium micronucleus (MNC) assay. The frequency of
      cells with MNC was highly correlated not only with bioconcentrated mercury (root
      mercury) but also with the levels of aquatic mercury. The threshold assessment
      values such as effective concentration fifty (EC50) for root growth, lowest
      effective concentration tested (LECT), and highest ineffective concentration
      tested (HICT) for induction of MNC in Allium MNC assay for the present aquatic
      industrial mercury were determined to be 0.14, 0.06 and 0.02 mg/l, respectively.

PMID- 1381478
TI  - Effects of supercypermethrin, a synthetic developmental pyrethroid, on four
      biological test systems.
AB  - The genotoxic potential of the insecticide supercypermethrin, a second-generation
      pyrethroid, was studied on four different test systems. It was non-mutagenic to
      Salmonella typhimurium strains TA1535, TA100, TA1538, TA98 and TA97 in the
      presence and absence of S9 mixture. It induced gene conversion at the tryptophan
      locus and induced point mutations at the isoleucine locus in Saccharomyces
      cerevisiae cells. A slight increase in the frequency of aberrant anaphases and
      telophases in root tips of Hordeum vulgare and Vicia faba was observed, but no
      genotoxic effects were detected in Drosophila melanogaster.

PMID- 1381479
TI  - Methyl parathion-induced sperm shape abnormalities in mouse.
AB  - Metacid 50, the commercial grade of methyl parathion (O,O-dimethyl-O-4
      nitrophenyl phosphorothionate), a commonly used organophosphorus insecticide, was
      tested for its genotoxicity in Swiss albino mice using the sperm abnormality
      assay. Sperms of albino mice were examined at two time intervals, 1 week and 5
      weeks after a single acute oral treatment with the pesticide at four dose levels,
      viz., 75.0, 37.5, 18.75 and 9.375 mg/kg body weight corresponding to 1/2 LD50,
      1/4 LD50, 1/8 LD50 and 1/16 LD50 values respectively. A dose-related
      statistically significant increase in the percentage of abnormal sperm observed
      indicates the genotoxic potency of methyl parathion.

PMID- 1381480
TI  - Genotoxicity of 2,4,6-trichlorophenol in V79 Chinese hamster cells.
AB  - The genotoxicity of the rodent carcinogen 2,4,6-trichlorophenol (TCP) was studied
      without exogenous metabolic activation in V79 Chinese hamster cells. TCP did not
      induce mutation at the hprt locus to 6-thioguanine resistance or structural
      chromosome aberrations. However, it produced statistically significant, dose
      related increases in hyperdiploidy and micronuclei. From these results it appears
      that TCP causes chromosome malsegregation as its major mode of genotoxic action.

PMID- 1381481
TI  - Detection of vincristine-induced hyperploidy in meiotic II metaphases of male
      Chinese hamsters.
AB  - Induction of hyperploidy in germ cells of male Chinese hamsters treated with
      vincristine at dose levels of 0.25, 0.50 or 0.75 mg/kg of body weight was
      investigated. Animals were killed at 6, 24, 48, 72 and 96 h after administration
      of the chemical by a single intraperitoneal injection. The testes were removed
      and processed for spermatogonial, meiotic I, and meiotic II metaphases.
      Significantly increased frequencies of hyperploidy were obtained in meiotic II
      cells harvested 6, 24 and 48 h but not 72 and 96 h after treatment, indicating
      the importance of multiple sampling times. Analysis of spermatogonial cells shows
      that the frequencies of hyperploidy in the treated samples were comparable to
      those of controls. Limited sampling times used in the present study as well as
      small sample size or possible loss of hyperploid cells may be responsible for the
      negative findings for spermatogonial cells. Examination of meiotic I cells from
      53 animals reveals the presence of one animal with an elevated level of
      hyperploidy unrelated to the vincristine treatment.

PMID- 1381482
TI  - The effect of gamma-irradiation on the toxicity of malathion in V79 Chinese
      hamster cells and Molt-4 human lymphocytes.
AB  - There is growing interest in the irradiation of food and agricultural products
      for insect disinfestation, sprout inhibition, delayed ripening and the reduction
      of microbiological loads. Extensive research has been done on this process, and
      irradiation to a maximum dose of 10 kGy is recognized as safe by national and
      international regulatory agencies. The question has been raised, however, whether
      irradiation of pesticide residues might produce radiation products that were more
      toxic or less toxic than the original pesticide. To address this question, we
      observed the effects of 10 kGy of gamma-radiation on malathion as measured by
      sister-chromatid exchange (SCE), micronuclei formation, cell survival, growth
      rate and polyploid formation. We found no significant differences between the
      effects of irradiated and unirradiated malathion on any of these end-points.
      Polyploid formation was the most dramatic effect of both irradiated and control
      malathion on V79 Chinese hamster cells. Cell survival, polyploid formation and
      growth rate were slightly better in cells treated with irradiated malathion. In
      Molt-4 human lymphocyte cells, micronuclei formation was not affected by
      irradiated or unirradiated malathion. Compared to malathion alone, the lack of
      such biological effects indicates that none of the presumed radiation-induced
      breakdown products increased or decreased the endpoints studied. The number of
      SCE was consistently, but not significantly, higher in the cells treated with
      irradiated malathion. There were no significant differences in cell survival or
      micronucleus formation in the human lymphocyte cell line Molt-4 treated with
      irradiated or control malathion. Thus, the irradiation of the pesticide malathion
      to 10 kGy, a recommended upper dose for most food irradiations, does not
      significantly alter its toxicity in these in vitro systems.

PMID- 1381483
TI  - The genotoxicity of organotin compounds in SOS chromotest and rec-assay.
AB  - In these days pollution by organotin compounds in the environment extends widely
      and effects on human health are feared. We studied the genotoxicity of various
      organotin compounds (butyltins, phenyltins, methyltins) and inorganic tin
      (SnCl4), which are present in the environment, with the SOS chromotest and the
      rec-assay. Mono-n-butyltin oxide, n-butyltin trichloride and di-n-butyltin
      dichloride showed high SOS-inducing potency in the SOS chromotest with
      Escherichia coli PQ37. Di-n-butyltin dichloride, tri-n-butyltin chloride, bis(tri
      n-butyltin)oxide, dimethyltin dichloride and trimethyltin chloride were
      recognized as genotoxic chemicals by the rec-assay.

PMID- 1381484
TI  - Genotoxicity assessment of pirmenol, a new antiarrhythmic drug.
AB  - The genotoxicity of pirmenol was tested in the E. coli and S. typhimurium
      mutagenesis assay, an in vitro mammalian cell chromosome-aberration assay and an
      in vivo mouse micronucleus assay. The E. coli tester strain WP2s was exposed to
      concentrations of pirmenol as high as 10,000 micrograms/plate both in the absence
      (S9-) and presence (S9+) of metabolic activation. Five strains of S. typhimurium
      (TA98, TA100, TA1535, TA1537, TA1538) were exposed to concentrations of pirmenol
      as high as 5000 micrograms/plate in the absence and presence of S9. Pirmenol was
      not mutagenic toward either E. coli or S. typhimurium. Chinese hamster lung V79
      cell cultures were exposed to pirmenol at concentrations of 500-2500
      micrograms/ml (S9-) and 500-3000 micrograms/ml (S9+). Pirmenol increased the
      frequency of structural chromosome aberrations (SCAs). The minimum clastogenic
      concentration was 1500 micrograms/ml (both S9- and S9+) with a peak clastogenic
      response of 6% (S9-) and 34% (S9+) cells with aberrations. Although there were
      statistically significant results in the S9- experiment, the percent cells with
      aberration values for treated groups were within the historical control range (0
      6%) of this laboratory. The observed effects in both the absence and presence of
      S9 appear at high concentrations compared to human circulating plasma levels of 1
      3 micrograms/ml and the clastogenicity was confined to chromosome gaps and
      breaks. Consequently, this in vitro effect would not be expected to be reflected
      by either in vivo clastogenic or carcinogenic activity. This was supported by
      findings in the mouse micronucleus study of pirmenol in which single oral doses
      administered to male CD-1 mice at 5, 55, or 115 mg/kg (80% LD50) produced no
      statistically significant increases in the frequency of micronucleated
      polychromatic erythrocytes in bone marrow at 24, 48 or 72 h postdosing.
      Additionally, no evidence of carcinogenicity was seen in a mouse or rat bioassay.

PMID- 1381485
TI  - A survey of lymphocyte chromosomal damage in Slovenian workers exposed to
      occupational clastogens.
AB  - Assays for sister-chromatid exchanges (SCE), unstable chromosome and chromatid
      aberrations and micronuclei were performed on blood lymphocytes from persons
      exposed protractedly to radiation or chemical hazards in the workplace. There was
      a general tendency with all endpoints examined for the yields to increase with
      years of working in the industry. This was especially marked for SCE. By
      comparison with a control group of administrative workers the levels of damage
      were higher, usually significantly so, in the occupational groups. These
      comprised workers at a nuclear research reactor, a hospital diagnostic X-ray
      department, a coal mine and a mercury ore mine.

PMID- 1381486
TI  - The genotoxicity status of sorbic acid, potassium sorbate and sodium sorbate.

PMID- 1381487
TI  - Sister-chromatid exchanges in human lymphocytes induced by dimethoate, omethoate,
      deltamethrin, benomyl and their mixture.
AB  - Dimethoate and omethoate, two common organophosphorus insecticides, induced a
      dose-related increase in the frequency of sister-chromatid exchanges (SCEs) in
      human lymphocytes in vitro (P of the regression lines less than 0.01). Two other
      common pesticides, the pyrethroid insecticide deltamethrin and the systemic
      fungicide benomyl, induced a modest increase in SCEs which bordered on
      statistical significance (P = 0.053 and 0.055, respectively). Mixtures of the
      four pesticides at total concentrations of 41.5 and 83 micrograms/ml (composed of
      43% dimethoate, 43% omethoate, 12% deltamethrin and 1.2% benomyl) induced a dose
      dependent increase in SCEs (P less than 0.01). The effects of these mixtures of
      pesticides were variable using lymphocytes from different individuals, although
      these differences did not attain statistical significance. Moreover, low
      concentrations of the four pesticides that did not increase SCEs significantly
      when tested alone, were positive for SCE induction when tested as a mixture. The
      experiments show that sub-threshold doses of pesticides may increase SCEs when
      present in a mixture.

PMID- 1381488
TI  - Evaluation of the ligase chain reaction (LCR) for the detection of point
      mutations.
AB  - The ligase chain reaction (LCR) was evaluated as an amplification method for an
      in vivo mutation assay. Specifically, the ligase was tested for its ability to
      selectively amplify a DNA sequence mutated at a single base, in the presence of
      an excess of wild-type DNA. As a model template a 370-bp DNA fragment of the
      mouse Ha-ras protooncogene containing an A to T mutation at the second position
      of codon 61 was used. With the commercially available ligase Ampligase
      (Epicenter), 250 molecules of mutant fragments could be detected by an enzyme
      linked immunoassay with digoxigenin marker (giving a theoretical detection limit
      of 1 target gene per 10(4) copies of genome). In the analysis of mixtures with
      corresponding wild-type DNA fragments, a 1:1 mixture resulted in a clearly
      stronger signal than control samples lacking wild-type and mutant DNA. However,
      the signal obtained from a 100-fold dilution of the mutant DNA with wild-type DNA
      could not be distinguished from the background noise. In this particular form,
      LCR lacks sufficient selectivity to be applied to an in vivo situation, where the
      ratio of mutant to wild-type DNA sequences might be expected to lie around
      1:10(6).

PMID- 1381489
TI  - Chinese hamster ovary cells deficient or proficient in O6-alkylguanine-DNA
      alkyltransferase activity are equally sensitive to X-rays.
AB  - In mammalian cells, under aerobic conditions, ionizing radiations and
      radiomimetic chemical agents can induce an enzymatic activity involved in DNA
      repair, O6-alkylguanine-DNA alkyltransferase (O6-AT). This catalytic protein is
      active against alkyl-radical-induced DNA damages. This induction was proposed to
      be linked to the formation of hydroxyl radicals. The possible involvement of O6
      AT in the defense mechanism of the cell against aerobic radiation damage was
      investigated by comparing the X-ray sensitivity of two Chinese hamster ovary
      (CHO) cell lines, the first deficient (CHO mex-) and the second proficient by
      transfection of O6-AT (CHO mex+). The colony-forming ability after X-irradiation
      was appreciably reduced in CHO mex- in comparison to CHO mex+ cells.
      Nevertheless, pretreatment of proficient cells with O6-methylguanine, a specific
      inhibitor of O6-AT, reduced the DNA repair activity but did not modify the degree
      of sensitivity to X-rays of the CHO mex+ cells. Since the glutathione
      concentrations as well as the DNA damage amounts induced by X-irradiation were
      comparable in the variously treated cell lines, these results suggest that the
      observed induction of O6-AT by ionizing radiation in aerobic conditions could be
      a generalized rather than a specific response to damage by radicals.

PMID- 1381490
TI  - Efficiency of DNA-histone crosslinking induced by saturated and unsaturated
      aldehydes in vitro.
AB  - Using a filter-binding assay based on precipitation of pUC13 plasmid DNA bound to
      calf-thymus histones, we have determined the efficiency of formation of DNA
      protein crosslink formation induced by several aldehyde compounds in vitro.
      Formaldehyde, glutaraldehyde and acrolein were the most potent, causing 1
      crosslink per 2.7 kbp of DNA at 1.5, 8 and 150 microM, respectively. All other
      compounds tested gave 1 crosslink per plasmid molecule in the mM concentration
      range as follows: acetaldehyde, 115 mM; propionaldehyde, 295 mM; butyraldehyde,
      360 mM; crotonaldehyde, 8.5 mM; trans-2-pentenal, 6.3 mM. Significant decreases
      in the efficiency of DPXL formation were observed with monofunctional aldehydes
      of higher carbon chain length. For example, the concentration of formaldehyde
      needed to give 1 crosslink per molecule was almost 10(5) times less than that of
      acetaldehyde. Acetaldehyde differs from formaldehyde only by one saturated
      carbon. The presence of an unsaturated bond between the 2-3 carbons improved the
      potential for crosslink formation. For example, acrolein was over 500-fold more
      potent than propionaldehyde. Glutaraldehyde was almost as potent as formaldehyde,
      indicating that the bifunctional nature of this 5-carbon saturated aldehyde may
      be crucial to its high efficiency of DNA-protein crosslinking.

PMID- 1381491
TI  - Lack of adaptive response to low doses of ionizing radiation in human lymphocytes
      from five different donors.
AB  - Various investigators reported a reduced yield of chromosome and chromatid
      aberrations in short-term cultures of human lymphocytes if a 'challenge' exposure
      to ionizing radiation was preceded by an 'adaptive' exposure. In order to examine
      the cell cycle dependence of the 'adaptive response', chromosome and chromatid
      aberration yields were estimated after challenge doses in the G1, S or G2 phase
      of lymphocytes which had been adapted in the early G1 phase. On testing two
      donors no protective adaptive response was found. Blood samples of four donors
      were tested for their capability to evoke the adaptive response in a standard
      experiment with the adaptive dose in the S phase and the challenge dose in the G2
      phase. A synergistic response occurred in one out of two similar experiments
      performed with the same blood sample. The three other blood samples tested did
      not respond. Apparently these data indicate a high frequency of human lymphocyte
      cultures that do not display an adaptive response.

PMID- 1381492
TI  - Mechanism of mutagenicity by 5-hydroperoxymethyl-2'-deoxyuridine, an intermediate
      product of ionizing radiation, in bacteria. HPMdU bacterial mutagenicity and
      oxidation of DNA bases.
AB  - The specific objective was to find what processes are responsible for the
      mutagenicity of 5-hydroperoxymethyl-2'-deoxyuridine (HPMdU), which is a product
      of ionizing radiation, and what role transition metal ions play in those
      processes. We found that HPMdU is a more potent mutagen than its decomposition
      products 5-hydroxymethyl-2'-deoxyuridine (HMdU) and 5-formyl-2'-deoxyuridine
      (FdU) in the Salmonella typhimurium strains tested, with the TA100 strain being
      the most sensitive. HMdU exerted intermediate mutagenicity and FdU was the
      weakest of the three compounds. At 50 nmoles/plate, HPMdU increased the number of
      revertants by 4-fold, whereas 1000 nmoles HMdU was required to enhance the number
      of revertants by 5-fold. Pretreatment of TA100 with o-phenanthroline, a membrane
      permeable Fe and Cu chelator, caused an increase in mutagenicity of the low HPMdU
      doses but inhibited that of the 50 nmoles HPMdU/plate, while desferal, a membrane
      impermeable Fe chelator, had virtually no effect. Azide (a catalase inhibitor)
      enhanced HPMdU mutagenicity, whereas 3-amino-1,2,4-triazole (a catalase and
      peroxidase inhibitor) and ammonium formate (a hydroxyl radical scavenger) were
      protective. Preincubation of TA100 cells with 20 and 40 nM HPMdU caused dose
      dependent formation of the oxidized DNA base derivatives HMdU, thymidine glycol
      and 8-hydroxyl-2'-deoxyguanosine (8-OHdG), known hydroxyl radical-mediated
      oxidation products. Cumulatively, these results suggest that the genetic effects
      of HPMdU are due to its hydroperoxide moiety, which upon reacting with Fe
      generates hydroxyl radicals that in turn oxidize neighboring bases in cellular
      DNA. This also may be a mechanism by which ionizing radiation exerts its long
      term effects.

PMID- 1381493
TI  - Influence of white blood cell count on SCE frequency in peripheral lymphocytes.

PMID- 1381494
TI  - Inorganic arsenic effects on human lymphocyte stimulation and proliferation.
AB  - Lymphocyte cultures from individuals exposed to high levels of hydroarsenicism
      showed a slower cell cycle kinetics than cultures from low-exposed individuals.
      Since this difference in proliferation could be due to chronic arsenic exposure,
      the in vitro effects of inorganic arsenic in human whole blood lymphocyte
      cultures were investigated. When lymphocytes were exposed to concentrations of
      arsenite and arsenate similar to those found in the blood of exposed subjects
      (10(-7), 10(-8) and 10(-9) M) during the last 24 h before harvesting, a dose
      related inhibition of proliferation was observed. Cultures were also treated with
      10(-9) M of arsenite and arsenate for 2, 6 and 24 h at the beginning of the
      cultures in the presence or absence of phytohemagglutinin (PHA). Inhibition of
      stimulation and proliferation was directly related to the length of treatment.
      The results show that, at the concentrations tested, arsenite and arsenate impair
      lymphocyte stimulation and proliferation and confirm the fact that chronic
      arsenic exposure can affect the proliferation of whole blood lymphocytes.

PMID- 1381496
TI  - Trypanosoma brucei mitochondrial ribosomal RNA synthesis, processing and
      developmentally regulated expression.
AB  - The steady-state levels of the mitochondrial ribosomal RNAs of Trypanosoma brucei
      are repressed in the early bloodstream developmental stage of the parasite and
      accumulate approximately 30-fold during differentiation to the stage found in the
      midgut of the insect vector. In order to determine the mechanism regulating this
      developmental process, we have examined the transcription and processing of the
      9S and 12S mitochondrial rRNAs of T. brucei. A short-lived RNA was detected in
      pulse labeling experiments which contains the mature 12S and 9S rRNAs and at
      least 1200 nucleotides of RNA transcribed from upstream of the 12S rRNA gene.
      This putative processing precursor RNA was identified in both intact cells and in
      run-on experiments using isolated mitochondria. The transcripts containing the
      upstream sequences are unstable and reach isotopic equilibrium within 15 min.
      Mature rRNAs in the insect developmental stage are stable and show no detectable
      turnover during a 36-h chase. Comparison of rRNA synthesis in bloodstream and
      insect life-stages indicates that mitochondrial rRNA levels are controlled not at
      the transcriptional level, but rather by a mechanism which likely modulates the
      stability of the mature rRNAs. These results suggest that a short-lived rRNA
      precursor is synthesized and processed at comparable rates in both bloodstream
      and insect stages of the parasite. Thus, it appears that differential stability
      of the mature 9S and 12S rRNAs plays a major role in modulating mitochondrial
      gene expression during the developmental cycle of T. brucei.

PMID- 1381495
TI  - Selective reactivities of isocyanates towards DNA bases and genotoxicity of
      methylcarbamoylation of DNA.
AB  - The reactivities of methyl isocyanate (MIC) and phenyl isocyanate (PIC) with DNA,
      and the genotoxicity of MIC were investigated. MIC and PIC reacted with the
      exocyclic amino group of deoxycytidine, deoxyadenosine and deoxyguanosine to
      produce carbamoylated products. The reactions of both isocyanates with
      deoxycytidine were 2 and 4 orders of magnitude higher than with deoxyadenosine
      and deoxyguanosine, respectively. To explore the genotoxicity of MIC, M13mp9 RF
      DNA was modified with MIC and then introduced into E. coli. The plaque-forming
      efficiencies of DNA decreased with increasing dose levels, and the decreases were
      more pronounced in Uvr endonuclease-deficient strains (uvrA, uvrB and uvrC) than
      in the Uvr endonuclease-proficient strain, JM103. The differences in survival in
      JM103 and uvr- strains suggest that the methylcarbonyl adducts can be removed by
      the uvr excision-repair system. Modification of M13mp9 RF DNA with MIC induced
      MIC-dose-related, SOS-dependent mutations in the beta-galactosidase locus. These
      results demonstrate the genotoxic response of MIC-modified DNA in E. coli.

PMID- 1381497
TI  - The effects of neuropeptides on mucous glycoprotein secretion from human nasal
      mucosa in vitro.
AB  - The role of neuropeptides in the regulation of macromolecule secretion from human
      nasal mucosa is incompletely understood. Previous in vitro explant culture
      studies have demonstrated the effects of neuropeptides on lactoferrin release
      from serous cells and 3H-glucosamine labeled respiratory glycoconjugate secretion
      from mucus-containing cells. The generation of a new monoclonal antibody, 7F10,
      has led to the development of an ELISA for high molecular weight respiratory
      mucous glycoproteins (MGP). This ELISA was used to measure the ability of
      sensory, parasympathetic and sympathetic neuropeptides to stimulate MGP release
      from human nasal mucosal fragments in short term explant culture in vitro.
      Significant MGP release was stimulated by the sensory neuropeptides gastrin
      releasing peptide (10 microM GRP: 10.6% +/- 2.4% increase, n = 8, P less than
      0.01 vs. control), substance P (1 microM SP: 12.5% +/- 5.4%, n = 11, P less than
      0.05), neurokinin A (1 microM NKA: 17.8 +/- 4.3%, n = 6, P less than 0.01), while
      calcitonin gene related peptide (CGRP) was without effect. Vasoactive intestinal
      peptide (VIP), a neurotransmitter from parasympathetic nerves, induced
      significant dose dependent MGP secretion, but had no additive or inhibitory
      interaction with methacholine-induced secretion. Neuropeptide Y (NPY), present in
      sympathetic nerves, had no effect on MGP secretion. These observations correlate
      with the effects of neuropeptides on serous cell lactoferrin secretion, and the
      presence of specific GRP, SP, and VIP binding sites on human nasal submucosal
      glands that have been detected by autoradiography. GRP and tachykinins (SP and
      NKA) from sensory nerves, and VIP released during parasympathetic reflexes may
      significantly stimulate mucous and serous cell secretion from human nasal mucosa
      in vivo.

PMID- 1381498
TI  - Presence of beta-2 microglobulin and alpha-2 macroglobulin in kappa AL
      amyloidosis.

PMID- 1381499
TI  - The poster session as a learning experience for master's students.

PMID- 1381500
TI  - Does Denver II produce meaningful results?

PMID- 1381501
TI  - Hydroxyl radical cleavage of tRNA in the ribosomal P site.
AB  - Hydroxyl radical is a useful probe of the accessibility of the sugar moiety of
      nucleic acids to solvent. Here we compare the accessibility of free and ribosome
      bound yeast tRNA(Phe), Escherichia coli tRNA(Phe), and E. coli tRNA(Leu2) to
      attack by hydroxyl radicals generated from Fe(2+)-EDTA. When bound to the P site
      of 30S ribosomal subunits, a discrete region, corresponding almost precisely to
      the anticodon stem-loop, is strongly protected; weaker protection is observed in
      the 3' strand of the D stem and in the variable loop. The protected nucleotides
      constitute a well-defined substructure, corresponding to the lower half of the
      anticodon-D loop coaxial arm of the tRNA crystal structure. This result suggests
      that the 30S P site contains a pocket that becomes inaccessible to the Fe(2+)
      EDTA complex when tRNA is bound, whose minimum dimensions can be inferred from
      the boundaries of the protected region of tRNA. When bound to the P site of 70S
      ribosomes, the entire tRNA backbone becomes inaccessible to hydroxyl radicals.
      Since previous studies have shown that virtually the entire footprint of a P-site
      tRNA on 16S and 23S rRNAs is mimicked by the extremities of the tRNA (the
      anticodon stem-loop plus the 3'-terminal aminoacyl-pentanucleotide), protection
      of the entire tRNA was unexpected. We conclude that protection of the elbow of
      tRNA is due either to interactions with ribosomal proteins or to enclosure in an
      inaccessible site formed by association of the two ribosomal subunits.

PMID- 1381502
TI  - Induction of cytotoxic T lymphocytes with peptides in vitro: identification of
      candidate T-cell epitopes in human papilloma virus.
AB  - A set of overlapping peptides corresponding to the L1, E6, and E7 proteins of
      human papilloma virus 16 was tested for their ability to bind to major
      histocompatibility complex class I molecules and to stimulate cytotoxic T
      lymphocyte (CTL) responses in vitro. A class I binding assay using intact RMA-S
      cells showed that 20 of the 99 human papilloma virus peptides bound to H-2Kb
      and/or Db molecules. Fifteen of the 20 class I-binding peptides stimulated
      primary CTL responses, whereas peptides that were negative in the binding assay
      failed to do so. Peptide-induced CTLs recognized the immunizing peptide very
      efficiently, requiring no more than 1-10 nM peptide for target cell lysis.
      However, two observations were made that have important implications for the
      design of peptide-based vaccines for inducing CTLs. (i) Not all major
      histocompatibility complex-binding peptides that contained known motifs
      characteristic of naturally processed peptides induced CTLs. (ii) The efficiency
      of CTL lysis was strongly decreased when the size of the target peptide differed
      by only one amino acid residue from that of the immunizing peptide. We conclude
      that peptides chosen for vaccination must correspond in length to naturally
      processed peptides.

PMID- 1381503
TI  - Structure of the CD59-encoding gene: further evidence of a relationship to murine
      lymphocyte antigen Ly-6 protein.
AB  - The gene for CD59 [membrane inhibitor of reactive lysis (MIRL), protectin], a
      phosphatidylinositol-linked surface glycoprotein that regulates the formation of
      the polymeric C9 complex of complement and that is deficient on the abnormal
      hematopoietic cells of patients with paroxysmal nocturnal hemoglobinuria,
      consists of four exons spanning 20 kilobases. The untranslated first exon is
      preceded by a G+C-rich promoter region that lacks a consensus TATA or CAAT motif.
      The second exon encodes the hydrophobic leader sequence of the protein, and the
      third exon encodes the amino-terminal portion of the mature protein. The fourth
      exon encodes the remainder of the mature protein, including the hydrophobic
      sequence necessary for glycosyl-phosphatidylinositol anchor attachment. The
      structure of the CD59 gene is very similar to that encoding Ly-6, a murine
      glycoprotein with which CD59 has some structural similarity. The striking
      similarity in gene structure is further evidence that the two proteins belong to
      a superfamily of proteins that may also include the urokinase plasminogen
      activator receptor and a squid glycoprotein of unknown function.

PMID- 1381504
TI  - Catalysis of serine and tyrosine autophosphorylation by the human insulin
      receptor.
AB  - The protein kinase activity of human insulin receptors purified from Sf9 insect
      cells after infection with a recombinant baculovirus was evaluated. The following
      experimental observations led to the unexpected conclusion that this receptor
      protein catalyzes both serine and tyrosine autophosphorylation at significant
      stoichiometries. (i) Phosphorylation of lectin-purified insulin receptors with
      [gamma-32P]ATP resulted in rapid receptor tyrosine phosphorylation (7 mol of P
      per high-affinity binding site) and the delayed onset of insulin-stimulated
      receptor serine phosphorylation (about 7% of total phosphorylation). The tyrosine
      kinase inhibitor (hydroxy-2-naphthalenylmethyl)phosphonic acid (HNMPA), which has
      no effect on protein kinase C or cyclic AMP-dependent protein kinase activities,
      inhibited both the receptor serine and tyrosine phosphorylation. (ii)
      Phosphorylation of a synthetic peptide substrate composed of insulin receptor
      residues 1290-1319 on serines-1305/1306 by partially purified insulin receptors
      was also inhibited by HNMPA. (iii) Insulin receptors sequentially affinity
      purified on immobilized wheat germ agglutinin and immobilized insulin showed no
      apparent contaminant proteins on silver-stained SDS/polyacrylamide gels yet
      catalyzed autophosphorylation on receptor serine and tyrosine residues when
      incubated with [gamma-32P]ATP. These results suggest that the catalytic site of
      the insulin receptor tyrosine kinase also recognizes receptor serine residues as
      substrates for the phosphotransfer reaction. Furthermore, insulin-stimulated
      receptor serine phosphorylation in intact cells may occur in part by an
      autophosphorylation mechanism subsequent to tyrosine phosphorylation of the
      insulin receptor.

PMID- 1381505
TI  - Targeted cleavage of mRNA by human RNase P.
AB  - Ribonuclease P from Escherichia coli can cleave RNAs in simple, hydrogen-bonded
      complexes of two oligoribonucleotides that resemble the aminoacyl stem and 5'
      leader sequence of tRNA precursors. RNase P from human (HeLa) cells cannot
      catalyze the cleavage in vitro of the 5'-proximal oligoribonucleotide that
      contains the leader sequence in such simple complexes but can do so when the 3'
      proximal oligoribonucleotide (external guide sequence) is altered to resemble
      three-quarters of a tRNA molecule. In such a complex, the efficiency of cleavage
      of the mRNA for chloramphenicol acetyltransferase, as the 5'-proximal
      oligoribonucleotide, depends on the structural details of the external guide
      sequence and on the choice of target site within the mRNA. The presence of the
      appropriately designed external guide sequence in cells in tissue culture reduces
      chloramphenicol acetyltransferase activity and the level of the corresponding
      intact mRNA in the cells. Thus, it appears that the use of such external guide
      sequences may provide a general technique for gene inactivation.

PMID- 1381506
TI  - Extracellular matrix regulates smooth muscle responses to substance P.
AB  - Little is known about the extracellular factors that determine a cell's
      responsiveness to neurotransmitters. This is a particularly important issue for
      pharmacologically diverse cell types such as neurons and smooth muscle. This
      report demonstrates that the contractile responses of amniotic smooth muscle to a
      specific neuropeptide, substance P, is controlled by a molecule(s) intimately
      associated with the extracellular basement membrane. This molecule(s) normally
      represses the expression of substance P responsiveness in this tissue. When the
      amniotic smooth muscle is separated from the basement membrane by dissociation,
      normally unresponsive cells exhibit a progressive increase in responsiveness to
      substance P, beginning within the first 24 hr in culture. The induction of
      substance P responses was completely inhibited when the cells were plated onto
      isolated amniotic basement membrane rather than onto polyornithine or collagen I.
      Similar changes in the responsiveness to another agonist, histamine, did not
      occur. The data demonstrate that extracellular matrix exerts a major instructive
      influence in determining the responsiveness of avian amniotic smooth muscle to
      specific ligands. We suggest that similar regulatory mechanisms may operate in
      other tissues.

PMID- 1381507
TI  - Purification of a murine protein-tyrosine/threonine kinase that phosphorylates
      and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene
      product.
AB  - We report the purification to near homogeneity of a 45-kDa phorbol ester
      stimulated protein kinase that phosphorylates and activates the Erk-1 gene
      product. This kinase, which we provisionally denote MEK for MAPK/Erk kinase,
      phosphorylated kinase-inactive Erk-1 protein primarily on a tyrosine residue and,
      to a lesser extent, on a threonine. We extend our previous results and show that
      two forms of purified MEK activated the myelin basic protein kinase encoded by
      Erk-1. MEK was inactivated by the serine/threonine phosphatase 2A but not by the
      protein-tyrosine phosphatase 1B. Sequence analysis of peptides generated by
      trypsin digestion of MEK revealed similarity to the proteins encoded by the
      Schizosaccharomyces pombe byr1 and Saccharomyces cerevisiae STE7 genes. These
      data are discussed with regard to a possible signal transduction mechanism.

PMID- 1381508
TI  - Increased tyrosine kinase activity of c-Src during calcium-induced keratinocyte
      differentiation.
AB  - In cultured human epidermal keratinocytes, induction of differentiation by Ca2+
      and ionophore treatment was found to result in rapid elevation of c-Src tyrosine
      kinase activity and inactivation of the c-Yes tyrosine kinase. Activation of c
      Src kinase was accompanied by tyrosine dephosphorylation, which might be
      explained by a rapid increase in intracellular protein-tyrosine phosphatase
      activity. Ca(2+)-induced differentiation was also associated with altered
      tyrosine phosphorylation of several cellular proteins and correlated with a
      marked redistribution of intracellular phosphotyrosine from membrane and adhesion
      sites to the nucleus. Some of the c-Src protein was also found in the nucleus
      after Ca2+ treatment, and Ca(2+)-activated c-Src bound to three cellular proteins
      (120 kDa, 65 kDa, and 34 kDa). In agreement with these results,
      immunohistochemistry on human epidermis revealed an increase in c-Src expression
      and tyrosine phosphorylation in cells undergoing differentiation, which strongly
      suggests a possible role of non-receptor tyrosine kinases in epithelial cell
      maturation.

PMID- 1381509
TI  - Inhibition of human immunodeficiency virus and growth of infected T cells by the
      immunosuppressive drugs cyclosporin A and FK 506.
AB  - The effects of the immunosuppressive drugs cyclosporin A and FK 506 were studied
      on cells chronically infected with human immunodeficiency virus type 1 (HIV-1) as
      well as on uninfected and newly infected cells. When cells chronically infected
      with HIV-1 or with HIV-2 were cocultivated with uninfected cells in the presence
      of cyclosporin A or FK 506 there was a delay in the formation of syncytia and of
      cytopathic effects. This inhibitory effect was not due to decreased membrane
      expression of CD4. In addition, there was an approximately 100-fold reduction in
      the yield of infectious HIV-1 when the infected cells were grown in the presence
      of these drugs, a finding consistent with other evidence of decreased HIV
      expression. Both drugs were found to inhibit the growth of chronically infected
      cells at concentrations that did not inhibit the growth of the uninfected cells.
      These results, demonstrating that cyclosporin A and FK 506 interfere with HIV
      production and selectively inhibit the growth of infected cells, suggest that
      they may be useful in the treatment of this infection and indicate further
      cellular targets for antiviral agents.

PMID- 1381510
TI  - [Peptide inhibitors of the renin-angiotensin system. 2. Polymer-bound tri-, penta
      and nonapeptide inhibitors of angiotensin converting enzyme].
AB  - Inhibitors of the angiotensin converting enzyme (ACE, EC 3.4.15.1) are important
      in the treatment of the high blood pressure. The therapeutically used drugs
      captopril, enalapril and ramipril are enzymatic stable short pseudo-peptides.
      They are stabilized against enzymatic degradation and therefore usefully for oral
      application. But for some indications e.g. post operative treatment and shock
      therapy well dosed infusions are needed. For this purpose we attached nona-,
      penta- and tripeptide inhibitors of the ACE to immunologically inert dextran
      polymers. The inhibitors are derived as well from the bradykinin potentiating
      nonapeptide BPP9 alpha (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) and the bradykinin
      potentiating pentapeptide BPP5 alpha (Pyr-Lys-Trp-Ala-Pro), both originally
      isolated from snake venoms, as from acylated tripeptides with the structure Acyl
      AA1-Arg-Pro. We estimated the influence on the biological activity of two
      different linkers to the dextran polymers. The coupling to the polymer was
      achieved on the one hand via the aldehyd moiety (DAD-AK) and on the other hand by
      the carboxyl residue (KMD). In the case of DAD-AK-polymers the condensation of
      the peptides was performed by the N-hydroxysuccinimide ester of the polymer.
      Because of the instability of the KMD-OSU in this case water soluble
      carbodiimides are used. The polymer bound peptides inhibit the isolated ACE, but
      in the most cases with a reduced activity. Only the tripeptide DPhe-Arg-Pro has a
      enhanced activity in the polymer bound state. The polymer bound inhibitors show a
      prolongated action on normotensive rats by intravenous application.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1381511
TI  - [The application of the problem-solving method in a situation of surgical
      intervention; a case report].
AB  - This study used the problems solving method for directing nursing assistance to
      the hospitalized surgical patient. We present the elaborate instrument founded in
      the Bailey e Claus model which is analyzed and exemplified. The authors consider
      the available resources concluding that the proposed is possible to be
      established. They realize how necessary is in nursing all the taking decision
      process to reach the proposed objectives, toward the resolution of the patient
      problems.

PMID- 1381512
TI  - Interleukins 9, 10, 11 and 12 and kit ligand: a brief overview.

PMID- 1381513
TI  - Comparison of L-5-hydroxytryptophan and L-5-hydroxytryptophan inosinate as agents
      for increasing brain serotonin formation in rats.
AB  - The effects of L-5-hydroxytryptophan (L-5HTP) and L-5HTP inosinate injection on
      brain 5-hydroxyindoles in rats were compared. L-5HTP and L-5HTP inosinate caused
      indistinguishable dose-dependent increases in 5HTP and 5HIAA (5
      hydroxyindoleacetic acid) but not serotonin concentrations in whole brain at 1 hr
      in rats. Our results do not substantiate a previous claim that L-5HTP inosinate
      is superior to L-5HTP itself in increasing brain serotonin formation.

PMID- 1381515
TI  - Human and murine monoclonal antibodies directed against a conserved sequence from
      gp41 (aa583-599) of human immunodeficiency virus type 1.
AB  - Human spleen cells from an HIV-seropositive donor were immunized in vitro with
      the aa583-599 peptide conjugated to an heptalysyl core. This sequence was derived
      from the putatively HIV-immunosuppressive region of HIV1 gp41. The same
      conjugated peptide was used to immunize mice. One human and one mouse IgM
      monoclonal antibody (mAb) directed against the aa583-599 peptide were obtained.
      The two mAb had distinct patterns of reactivity against a panel of 42 peptides
      with modified sequences. Neither of the mAb inhibited the immunosuppressive
      effect of aa583-599 octopus-lys-conjugated peptide on anti-CD3 Ab-induced
      lymphoproliferation. In addition, both mAb did not neutralize cell-free virus
      transmission or enhance HIV infection. However, HmAb inhibited formation of
      syncytia between HIV1-infected (but not HIV2-infected cells) and non-infected
      target cells at concentrations above 20 micrograms/ml, whereas MmAb did not have
      any effect. The degree of conservation of the aa583-599 region makes HmAb a
      candidate for use as a group-specific reagent in future HIV1 passive
      immunotherapy protocols.

PMID- 1381514
TI  - Detection of potyviruses with antisera to synthetic peptides.
AB  - Eight peptides corresponding to conserved regions of the coat protein of
      potyviruses were synthesized. All the peptides were recognized by anti-virus or
      anti-core-virus. Antisera raised to the synthetic peptides were tested with
      purified viruses and viral antigens present in plant sap. In many cases, the
      extent of cross-reactivity between different potyviruses was not correlated with
      the degree of sequence homology between the peptide used for immunization and the
      corresponding region in the coat protein of the potyvirus tested. An antiserum
      raised to a peptide of 18 residues containing a highly conserved region was found
      to react with all seven potyviruses tested.

PMID- 1381516
TI  - [A case of medically treated type A acute aortic dissection: trial of
      antifibrinolytic therapy while monitoring the thrombotic and fibrinolytic
      parameters].
AB  - A 56-year-old male was admitted with severe chest and abdominal pain. Enhanced CT
      revealed type-A acute aortic dissection. Enhancement of false lumen was complete
      in the aortic arch, but it was incomplete in the ascending and descending aorta.
      This finding suggested a thrombosing tendency of the false lumen. Marked
      elevation of Thrombin-Antithrombin III complex (TAT) and Plasmin-alpha 2 Plasmin
      inhibitor complex (PIC) indicated the activation of both coagulation and
      fibrinolysis in the false lumen. Aprotinin and Tranexamic acid were used in order
      to suppress the fibrinolysis. Both TAT and PIC were completely normalized at the
      20th hospital day. Enhanced CT on the 40th hospital day showed that the false
      lumen had disappeared, and the adventitia had thickened. Care should be taken to
      notice activated coagulation and fibrinolysis in the false lumen. This report
      appears to be the first statement about the effectiveness of antifibrinolytic
      therapy to facilitate thrombosing and healing of the false lumen in the treatment
      of acute aortic dissection.

PMID- 1381517
TI  - A monoclonal antibody-based immunodiagnostic assay for onchocerciasis.
AB  - Five murine monoclonal antibodies raised against Onchocerca volvulus cuticular
      extracts and termed MOVs (1-4 and 6) were selected based on reactivity with O.
      volvulus cryosections, and non-reactivity with cryosections of human skin and/or
      nodular tissue. Two others MOVs 5 and 7 reacted with both. Using the peroxidase
      anti- peroxidase (PAP) histochemical method, the target epitopes of MOV 1 were
      located in the cuticle's basal and cortical layers, those of MOV 2 in the
      cortical layer; whilst MOV 3-7 stained the basal layer. A sandwich ELISA was then
      developed. The trapping polyclonal antibody was raised in rabbits utilising the
      same antigens as for preparation of the MOVs. Once captured on microtiter plates,
      target antigens were identified by the sequential binding of a MOV, followed by a
      goat anti-mouse globulin/peroxidase or alkaline phosphatase conjugate that
      catalysed a colorimetric reaction in the presence of appropriate substrates. In
      this system, MOV 1 emerged as the most specific and potent reagent capable of
      recognizing antigens of Onchocerca sp. with a minimal detection limit of 78 ng
      per test. MOV 1, failed to react with extracts of Loa Loa, Ascaris lumbricoides
      and Ascaris suum in the test. The developed assay relied on the use of MOV 1,
      required only 1 ml of urine or 0.05 ml serum. About 97.8% of the 47 urines and
      50% of the 20 sera from patients studied gave positive results. Only 1 (3%) of 32
      control urines and up to 80% of the 10 control sera studied tested positive,
      suggesting urine as a better specimen source.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381518
TI  - The T-cell repertoire in myasthenia gravis involves multiple cholinergic receptor
      epitopes.
AB  - Antibodies against the alpha-subunit of the acetylcholine receptor (AChR) are
      found in most patients with myasthenia gravis and are considered to contribute to
      the receptor damage which leads to the characteristic signs and symptoms of the
      disease. This B-cell response is T-cell driven. Elevated T-cell reactivities to
      AChR and its alpha-subunit have been described in myasthenia gravis, and AChR
      alpha-subunit peptide reactive T-cell lines and clones preferentially recognizing
      certain defined sequence segments have been reported, thereby disclosing the
      possibility of specific immunotherapy. We have defined the T-cell repertoire to
      AChR, its alpha-subunit and the synthetic peptide sequences 100-117, 113-130, 143
      163, 161-179, 207-225, 221-240, and 235-255 of the alpha-subunit in an immunospot
      assay which is based on secretion of interferon-gamma (IFN-gamma) by individual
      memory T cells upon stimulation with specific antigen in short-term cultures.
      Most patients with myasthenia gravis displayed T-cell reactivities to 1 to 6
      different peptides. The mean numbers of T cells recognizing individual peptides
      varied in the myasthenia gravis patients between 1 per 77,000 and 1 per 167,000
      peripheral blood mononuclear cells. None of the seven peptides evaluated could be
      identified as an immunodominant T-cell epitope, and any of them was found to
      dominate in individual patients. The numbers of T cells reacting with AChR and
      recombinant human AChR alpha-subunit were slightly higher (mean numbers 1 per
      26,000 and 1 per 50,000 mononuclear cells, respectively). Such cells, as well as
      AChR alpha-subunit peptide reactive T cells, were also found in patients with
      other neurological diseases and in healthy subjects, but at lower frequencies and
      numbers. In myasthenia gravis, the elevated numbers of memory T cells recognizing
      multiple AChR alpha-subunit peptides may be crucial for the development of the
      disease, and the IFN-gamma released by such T cells might be important for its
      perpetuation.

PMID- 1381519
TI  - T-cell epitopes on the human acetylcholine receptor alpha-subunit residues 10-84
      in myasthenia gravis.
AB  - In myasthenia gravis the production of anti-acetylcholine receptor antibodies is
      modulated by acetylcholine receptor-specific T cells. Most B- and T-cell epitopes
      are located on the alpha-subunit of the receptor. In order to map the fine
      specificity of the antigen-specific T cells in myasthenia gravis, T-cell
      stimulation in response to 70 hexapeptides was studied in 24 patients and 24
      healthy individuals. The hexapeptides overlapped with one amino acid and
      represented residues 10-84 of the NH2-terminal part of the alpha-subunit of the
      receptor. The IFN-gamma secretion from single T cells was used to detect T-cell
      stimulation. A significant difference in the T-cell response to several of the
      peptides was found between patients and healthy controls. The majority of the
      hexapeptides induced T-cell stimulation in at least one of the patients. Peptide
      induced T-cell stimulation was evident in all but one of the patients. The
      results indicate that different epitopes and multiple T-cell clones are involved
      in the T-cell recognition of the acetylcholine receptor.

PMID- 1381520
TI  - The effect of calcium mobilization on LPS-induced IL-1 beta production depends on
      the differentiation stage of the monocytes/macrophages.
AB  - The role of elevated intracellular calcium concentration [Ca2+]i in the LPS
      induced activation of interleukin-1 beta (IL-1 beta) production was examined in
      cells representing different stages of myeloid differentiation (undifferentiated
      monocytic leukaemia cell line THP-1, THP-1 cells induced to adherent, macrophage
      like cells by phorbol ester treatment and normal peripheral blood-derived
      adherent monocytes). LPS did not elevate the [Ca2+]i as measured by the Fura-2
      fluorescence technique. When these cells were stimulated with LPS in the presence
      of the calcium ionophore A23187, a clear increase in the IL-1 beta protein
      production was observed in the undifferentiated THP-1 cells but not in the more
      differentiated cell types. This ionophore-induced increase was also seen in the
      IL-1 beta mRNA levels. Thus these data confirm the previous findings
      demonstrating that elevation of [Ca2+]i is not involved in the LPS-dependent
      signal transmission. However, the LPS-induced signals are greatly potentiated by
      the elevated [Ca2+]i, but only in undifferentiated monocytic cells.

PMID- 1381521
TI  - Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by
      spinal cyclooxygenase inhibition.
AB  - Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs (NSAIDs) in
      the periphery is commonly accepted as the primary mechanism by which these agents
      produce a selective attenuation of pain (analgesia). NSAIDs are now shown to
      exert a direct spinal action by blocking the excessive sensitivity to pain
      (hyperalgesia) induced by the activation of spinal glutamate and substance P
      receptors. These findings demonstrate that the analgesic effects of NSAIDs can be
      dissociated from their anti-inflammatory actions. Spinal prostanoids are thus
      critical for the augmented processing of pain information at the spinal level.

PMID- 1381522
TI  - Women and access to health care.
AB  - This paper is concerned with access to health care for women in developing
      countries, with specific reference to Latin American and Caribbean countries. It
      reviews the available literature on the concept of access as it relates to other
      variables such as accountability, affordability and acceptability of health
      services, taking into consideration the effects of the generalized socio-economic
      crisis that has affected most countries during the last decade, as well as equity
      objectives. Various approaches to defining variables affecting access to health
      care appear in the literature reviewed. While some of them indicate that ability
      to pay for services act as a major determinant of access to health care, others
      point to behavioral issues related to motivation, health seeking behavior or
      perception of illness as a deterrent to women in the low socioeconomic strata,
      while others indicate that sociocultural issues, such as values, education,
      religion or demographic variables related to age, influence access to health
      care. The paper concludes with some comments on policies and strategies for
      securing access to health and healthcare, indicating the need to move away from
      traditional solutions including framing gender-based health differences in status
      and access adequately, promoting and strengthening social participation of women
      in policy making.

PMID- 1381523
TI  - [Radiologic diagnosis during conservative and surgical treatment of bone
      injuries].

PMID- 1381524
TI  - Aprotinin increases release of von Willebrand factor in cultured human umbilical
      vein endothelial cells.
AB  - Through the perioperative administration of the proteinase inhibitor aprotinin,
      hemostasis can be improved and postoperative bleeding reduced after cardiac
      operations. The mechanism of action has been only partially clarified. The goal
      of our study was to investigate the influence of aprotinin on the synthesis of
      von Willebrand factor (vWF) in human endothelial cells. Human umbilical vein
      endothelial cells (HUVEC) were cultivated in vitro and incubated with different
      aprotinin concentrations (55, 100, and 215 mol/L). With all investigated
      aprotinin concentrations, there was an increase in vWF synthesis compared with
      basal secretion (p less than 0.001). When the HUVEC were preincubated with
      aprotinin and stimulated with thrombin, there was a further significant increase
      in vWF synthesis. HUVEC that, were first incubated with aprotinin and then
      stimulated with thrombin demonstrated a significant increase in vWF synthesis
      compared with basal secretion in nonincubated cells (p less than 0.0001). Also,
      compared with the cells that had received thrombin stimulation alone, the
      combination of aprotinin incubation and thrombin stimulation led to a
      significantly higher vWF concentration (p less than 0.05). Because vWF is
      necessary for the interaction with platelet factor glycoprotein Ib and platelet
      adhesion, the demonstrated increase in vWF synthesis could be one of the
      mechanisms of action of aprotinin leading to its blood-sparing effect.

PMID- 1381525
TI  - Acute radiation enteritis in rats: bile salts and trypsin.
AB  - Surgically exteriorized rat intestine divided into segments containing saline
      solution, a bile salt binder, or a trypsin inhibitor were radiated (1100 cGy) and
      subsequently evaluated for histologic damage. Five days after radiation, crypt
      cell numbers, mucosal height, and mucous cell numbers were significantly greater
      in segments protected by the binding of bile salts or the absence of trypsin
      activity compared with saline-bathed mucosa. Thus both proteolytic enzymes and
      bile salts in the lumen contribute to the acute enteritis that follows a single
      dose of x-radiation.

PMID- 1381526
TI  - [The mechanism of tachycardic arrhythmias].
AB  - The mechanisms of cardiac tachyarrhythmias are discussed on the basis of
      experimental animal studies. Two major mechanisms are discussed in detail:
      membrane oscillations arising form electrically unstable cells and acting as
      ectopic foci of a tachycardia, and disturbances of impulse propagation which
      cause vortex-like circulating excitation with re-entry. These vorteces from the
      origin of the re-entrant tachycardias and of ventricular fibrillation.

PMID- 1381527
TI  - Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored
      at 22 degrees C.
AB  - Platelets stored in CLX blood bags, under normal blood banking conditions, were
      studied for up to 7 days to determine if changes occurred in the levels of
      membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal
      antibodies (MAB) were used to estimate the number of glycoprotein molecules on
      the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained
      essentially unaltered during storage. In contrast, the content of GP Ib at day 7
      decreased by 45% of the total when fresh. The aggregation response to ristocetin,
      which requires GP Ib, was also diminished after 7 days. Addition of protease
      inhibitors, leupeptin and/or aprotinin did not appear to influence the
      degradation of this glycoprotein. We conclude that storage at 22 degrees C had
      deleterious effects on the GP Ib content of platelets.

PMID- 1381528
TI  - Multimeric analysis of von Willebrand factor by vertical sodium dodecyl sulphate
      agarose gel electrophoresis, vacuum blotting technology and sensitive
      visualization by alkaline phosphatase anti-alkaline phosphatase complex.
AB  - To detect von Willebrand factor multimers in plasma samples and factor VIII
      concentrates, a vertical discontinuous SDS electrophoresis was developed. A
      vacuum blotting system allowed to improve the transfer to the nitrocellulose
      membrane. The visualization of the separated multimers was sensitized by applying
      an alkaline phosphatase anti-alkaline phosphatase staining technique. The
      reported method clearly shows structural abnormalities of von Willebrand factor
      and deficiency of high multimers, the vacuum transfer is efficient and the
      sensitivity of the staining system is very high.

PMID- 1381529
TI  - Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat
      focal ischemia.
AB  - BACKGROUND AND PURPOSE: Neutrophils are critically involved with ischemia and
      reperfusion injury in many tissues but have not been studied under conditions of
      reperfusion after focal cerebral ischemia. The present studies were conducted to
      confirm our previous observations quantifying neutrophils in rat permanent focal
      stroke using a myeloperoxidase activity assay and to extend them to transient
      ischemia with reperfusion. In addition, leukotriene B4 receptor binding in
      ischemic tissue was evaluated as a potential marker for inflammatory cell
      infiltration. METHODS: Histological, enzymatic, and receptor binding techniques
      were used to evaluate neutrophil infiltration and receptor binding in infarcted
      cortical tissue 24 hours after permanent middle cerebral artery occlusion (n =
      25) or temporary occlusion for 80 (n = 12) or 160 (n = 22) minutes followed by
      reperfusion for 24 hours in spontaneously hypertensive rats. RESULTS: Sham
      surgery (n = 26) produced no changes in any parameter measured. After permanent
      middle cerebral artery occlusion, neutrophil accumulation was observed
      histologically, but the infiltration was moderate and typically within and
      adjacent to blood vessels bordering the infarcted cortex. After temporary middle
      cerebral artery occlusion with reperfusion, marked neutrophil infiltration was
      observed throughout the infarcted cortex. Myeloperoxidase activity was increased
      (p less than 0.05) after permanent occlusion and to a greater extent after
      temporary occlusion with reperfusion. Myeloperoxidase activity (units per gram
      wet weight) in ischemic cortex was increased over that in nonischemic (control)
      cortex 32.2-fold, 54.6-fold, and 92.1-fold for permanent occlusion and 80 and 160
      minutes of temporary occlusion with reperfusion, respectively (p less than 0.05).
      Sham surgery produced no changes in myeloperoxidase activity. Leukotriene B4
      receptor binding also was increased (p less than 0.05) after focal ischemia and
      paralleled the increases in myeloperoxidase activity. Ischemic cortex-specific
      receptor binding (femtomoles per milligram protein) was 3.87 +/- 0.63 in sham
      operated rats and 4.57 +/- 0.98, 8.98 +/- 1.11, and 11.12 +/- 1.63 for rats
      subjected to permanent occlusion and 80 and 160 minutes of temporary occlusion
      with reperfusion, respectively (all p less than 0.05 different from sham
      operated). Cortical myeloperoxidase activity was significantly correlated with
      the degree of cortical leukotriene B4 receptor binding (r = 0.66 and r = 0.79 in
      two different studies, p less than 0.01). CONCLUSION: These data indicate that
      neutrophils are involved in focal ischemia and that there is a dramatic
      accumulation of neutrophils in infarcted tissue during reperfusion that can be
      quantified using the myeloperoxidase activity assay. Leukotriene B4 receptor
      binding increases in infarcted tissue in a parallel manner, which suggests that
      the increased leukotriene B4 binding is to receptors located on the accumulating
      neutrophils.

PMID- 1381530
TI  - Therapeutic monitoring of cyclosporine, FK-506, and rapamycin.

PMID- 1381533
TI  - The use of recombinant granulocyte-colony-stimulating factor for granulocyte
      harvest.

PMID- 1381532
TI  - Prestorage removal of Yersinia enterocolitica from red cells with white cell
      reduction filters.
AB  - Prestorage removal of phagocytic white cells (WBCs) may increase the
      survivability of contaminating bacteria in units of stored red cells. Fourteen
      units of whole blood were inoculated with 65 colony-forming units per mL of
      Yersinia enterocolitica (serotype O:3) and processed into AS-3-preserved red
      cells. Five red cell units were filtered with a prototype third-generation filter
      and five red cell units with a second generation filter. WBC reduction was
      performed on the day of collection. Four red cell units were not filtered. Three
      noninoculated whole blood units served as negative controls; two were filtered
      (one with each type of WBC-reduction filter) and one remained unfiltered. All red
      cell units were then stored at 4 degrees C for 42 days. One of the five filtered
      red cell units (20%) in each filter group supported growth of Y. enterocolitica.
      In contrast, 4 (100%) of 4 unfiltered inoculated red cell units had growth (p =
      0.04). Overall, 2 (20%) of 10 units of WBC-reduced red cells supported the growth
      of Y. enterocolitica, as compared to 100 percent of unfiltered red cell units
      after inoculation (p = 0.015). Bacterial contamination was not detected in any of
      the three noninoculated units. It can be concluded that prestorage WBC filtration
      significantly reduces the potential for growth of Y. enterocolitica in red cells
      stored at 4 degrees C for 42 days.

PMID- 1381531
TI  - Enzyme-linked immunosorbent assay for the detection of substances that carry
      blood group A specificity.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed to estimate the amount
      of material carrying blood group A activity in biologic samples. A soluble
      synthetic form of the A antigenic determinant (A trisaccharide, ATS) conjugated
      to peroxidase competes with the blood group A substance present in a biologic
      sample for anti-A attached to a solid phase by a second antibody coating the
      plastic micro-wells. A reference curve is constructed by using known quantities
      of ATS to compete with a fixed amount of ATS-peroxidase conjugate. The A
      substance activity in a sample is obtained by extrapolating the degree of
      inhibition of the binding of the ATS-peroxidase conjugate to an equivalent amount
      of ATS in the reference curve. The assay is reproducible, specific, and
      sensitive. It has been used in pharmacologic studies to estimate the
      concentration of ATS in the blood and urine of rats, rabbits, and baboons and in
      a study with human samples, testing the potential clinical use of ATS to
      neutralize anti-A when therapeutically indicated. It is also useful for the
      detection of ABO natural products in secretions, thus allowing the accurate
      classification of secretor and nonsecretor individuals.

PMID- 1381534
TI  - [Determination of melittin antigenic determinants in a model membrane].
AB  - Monospecific polyclonal antibodies labelled with colloid gold were obtained
      against melittin in different conformations (monomer, tetramer and complex with
      BSA). They were used for electron analysis of the position of antigenic
      determinants of melittin in DMPC model membrane. The antibodies reacted in cross
      immunoassay in different titres with all antigenes and this evidences for the
      presence of common antigenic determinants in their structures. It was found that
      melittin antigenic determinants in the model membrane are exposed and accessible
      to reaction with antibodies and, therefore, they serve the agent for stimulation
      of immune response and production of antibodies.

PMID- 1381535
TI  - The replication of cymbidium ringspot tombusvirus defective interfering-satellite
      RNA hybrid molecules.
AB  - A DNA copy of DI RNA of cymbidium ringspot tombusvirus was cloned downstream of a
      phage T7 promoter. In vitro-transcribed RNA replicated in Nicotiana clevelandii
      when co-inoculated with full-length viral genomic RNA transcripts and protected
      plants from apical necrosis. Artificial deletion mutants derived from the DI RNA
      clone showed that most of the central sequence block is necessary for
      replication. Hybrid DI RNA-satRNA clones were prepared and in vitro-synthesized
      RNA was inoculated to plants in the presence of helper viral RNA. There was
      replication only of in vitro transcripts derived from hybrid clones where satRNA
      sequences were inserted upstream or downstream from the central block, but not of
      those derived from clones where satRNA sequence replaced the central block.
      Progeny RNA of biologically active clones was either full-length or showed
      deletions depending on the insertion of satRNA sequences in DI RNA. DI RNA-satRNA
      constructs having part of the 5' region exchanged were not replicated.

PMID- 1381536
TI  - Processing of linear longer-than-unit-length potato spindle tuber viroid RNAs
      into infectious monomeric circular molecules by a G-specific endoribonuclease.
AB  - Different cDNA constructs were used for the in vitro synthesis of RNA transcripts
      that contain a complete monomeric unit of the potato spindle tuber viroid (PSTVd)
      plus an additional repeat of a part of the circular RNA genome. These permutated
      linear longer-than-unit-length PSTVd RNAs were incubated with the G-specific
      endoribonuclease RNase T1 which generated monomeric circular PSTVd RNA molecules
      that were infectious when mechanically inoculated to tomato plants. Besides the
      correct monomeric PSTVd RNA, smaller and larger circular RNAs were also formed
      during the reaction. The comparison of different transcripts revealed that
      correct in vitro processing of PSTVd RNA can proceed at alternative sites
      indicating that circularization is driven by RNA structure and not governed by a
      particular sequence. Based on these data, we propose a novel model for the
      processing of multimeric replicative viroid RNA intermediates through RNA
      cleavage and ligation catalyzed by a host endoribonuclease.

PMID- 1381537
TI  - Epitope mapping of the gp53 envelope protein of bovine viral diarrhea virus.
AB  - Epitopes recognized by nine monoclonal antibodies (mAbs) on the envelope protein,
      gp53, of two strains of bovine viral diarrhoea virus (NADL and Oregon C24V) were
      mapped by competitive binding assays and by the characterization and sequence
      analyses of mAb neutralization escape mutants. This defined an antigenic domain
      on gp53 that was shared by many BVDV strains, while other less conserved epitopes
      were possibly distinct. Sequencing of escape mutant viruses revealed that a
      cluster of three amino acids in the N-terminal half of gp53 were involved in the
      main antigenic domain shared by both NADL and Oregon C24V viruses, while an amino
      acid 31 residues further toward the N-terminus was involved in a second site
      present only on the NADL strain. Since other amino acids defining these epitopes
      were located at distant positions within the gp53 protein, it is likely that a
      major domain [corrected] on gp53 consist of composite, conformation-dependent
      epitopes.

PMID- 1381538
TI  - Presentation of hepatitis B virus preS2 epitope on bluetongue virus core-like
      particles.
AB  - A chimeric protein containing most of the hepatitis B virus preS2 region (amino
      acid residues 1-48) upstream to, and colinear with the amino-terminus of
      bluetongue virus VP7 protein (preS2-VP7) was expressed by a recombinant
      Autographa californica nuclear polyhedrosis virus (AcNPV). The chimeric protein
      formed BTV core-like particles (CLPs) in Spodoptera frugiperda cells only when
      the cells were coinfected with this recombinant virus and a recombinant
      baculovirus that expresses unmodified VP7 and VP3 of BTV. The ratio of preS2-VP7
      incorporated into CLPs was influenced by the relative multiplicities of infection
      of the two viruses. Immunoelectron microscopy of the chimeric particles indicated
      that the preS2 epitope was exposed on the surface of the CLPs. When insect cells
      were coinfected with the preS2-VP7 recombinant virus and a baculovirus vector
      that synthesized only the VP3 protein, no CLPs were identified.

PMID- 1381539
TI  - Biologically selected recombinants between feline leukemia virus (FeLV) subgroup
      A and an endogenous FeLV element.
AB  - In efforts to elucidate the proximal leukemogens that might be produced during a
      feline leukemia virus (FeLV) infection of cats, homologous recombinations between
      molecularly cloned exogenous and endogenous FeLV proviruses of known sequences
      were examined in cell cultures in vitro. A plasmid containing an infectious
      member of the most commonly occurring FeLV subgroup (FeLV subgroup A or FeLV-A)
      was coexpressed with noninfectious constructs containing the envelope (env) gene
      of an endogenously inherited FeLV-like feline genomic element in transfected
      feline fibroblasts. The viruses generated were selected for their ability to
      propagate in human cells which are resistant to infection by the parental
      ecotropic FeLV-A or the noninfectious endogenous constructs. An analysis of the
      recombinants thus derived identified a limited number of sites in the env gene
      which were preferentially utilized in the generation of recombinant FeLVs under
      the selection conditions used. These sites were clustered in the surface
      glycoprotein (SU) moiety of the env gene, and it appeared that most, but not all,
      of the SU gene product of FeLV-A, beginning from the N-terminus, can be replaced
      by sequences from an endogenous element, still allowing the virus to be
      biologically viable. In fact, these substitutions in the env gene expanded
      infectivity of the parental FeLV-A from ecotropic to polytropic cell tropism.
      Additionally, substitutions in the SU region yielded many recombinants in which a
      primary neutralizing pentapeptide epitope of FeLV-A was altered because of its
      variance in the endogenous element. In several of the recombinants, this sequence
      was also found to be frequently mutated. Consistent with the changes identified
      in this antibody-binding domain, the recombinant viruses were only weakly
      inhibited by a monoclonal antibody directed against this epitope, while FeLV-A
      was highly sensitive to neutralization.

PMID- 1381540
TI  - Interferon-inducible gene expression in chimpanzee liver infected with hepatitis
      C virus.
AB  - The molecular host response to hepatitis C virus (HCV) infection was examined by
      isolation of HCV-induced genes from a cDNA library constructed from chimpanzee
      liver during the acute phase of hepatitis C. Two cDNA clones, 130-7 and 130-51,
      were obtained by differential hybridization with cDNA probes prepared from
      poly(A)+ RNAs of infected and uninfected livers. Northern blot analysis revealed
      that the 130-7 and 130-51 cDNAs were expressed as 1.5- and 1.0-kb products,
      respectively, in chimpanzee liver and that their induction rates of the two were
      20 and 4, respectively. Nucleotide sequence analyses of these cDNA inserts showed
      that the sequence of cDNA 130-7 was that of a class I major histocompatibility
      antigen and that the sequence of cDNA 130-51 was 98% homologous with a human
      interferon-inducible mRNA. These results suggest that HCV infection may actively
      induce interferon, which in turn induces the expressions of these interferon
      inducible genes. Furthermore, the high expression of HLA class I antigen in the
      acute phase of hepatitis C suggests that liver cell injury in HCV infection may
      be mediated by cytotoxic T cells that recognize viral antigen in association with
      HLA class I antigen.

PMID- 1381541
TI  - The influence of N-linked glycosylation on the antigenicity and immunogenicity of
      rubella virus E1 glycoprotein.
AB  - Rubella virus E1 glycoprotein contains three functional N-linked glycosylation
      sites. The role of N-linked glycosylation on the antigenicity and immunogenicity
      of E1 glycoprotein was studied using vaccinia recombinants expressing E1
      glycosylation mutants. Expressed E1 glycosylation mutant proteins were recognized
      by a panel of E1-specific monoclonal antibodies in radioimmunoprecipitation,
      immunofluorescence, and immunoblotting, indicating that carbohydrate side chains
      on E1 are not involved in the constitution of epitopes recognized by these
      monoclonal antibodies. This observation was further supported by the fact that
      removal of oligosaccharides on E1 by glycosidase digestion did not significantly
      change the antigenicity of E1. All the glycosylation mutants were capable of
      eliciting anti-RV E1 antibodies. The single glycosylation mutants (G1, G2, and
      G3), but not the double mutant (G23) or the triple mutant (G123), were found to
      be capable of inducing virus neutralizing antibodies. Among the single
      glycosylation mutants, only G2 and G3 were active in producing hemagglutination
      inhibition antibodies in mice. Our findings suggest that although carbohydrate on
      E1 is not directly involved in the antigenic structures of E1, it is important in
      maintaining proper protein folding and stable conformation for expression of
      immunological epitopes on E1.

PMID- 1381542
TI  - [Multi-visceral upper abdominal resection and orthotopic liver transplantation--a
      surgical treatment concept for regionally metastatic tumors of the endocrine
      pancreas].
AB  - Islet cell carcinoma is rare. Even in advanced metastasizing tumors, relatively
      long survival times were reported. Aim of surgical treatment is complete removal
      of the tumor mass, if possible. When not, palliative procedures were described to
      be efficient in some of the cases. In the literature, among the first patients
      with regional metastasizing intraabdominal malignancies and upper abdominal
      exenteration, some cases with neuroendocrine tumors were reported. Aim of the
      following study is to describe the results in 4 patients with metastasizing islet
      cell carcinomas, which were treated by multi-visceral upper abdominal
      exenteration and combined orthotopic liver transplantation.

PMID- 1381543
TI  - Enhanced effect of mutant granulocyte-colony-stimulating factor (KW-2228) on the
      growth of normal and leukemic hemopoietic progenitor cells in comparison with
      recombinant human granulocyte-colony-stimulating factor (G-CSF).
AB  - We tested the in vitro effect of a novel granulocyte colony-stimulating factor (G
      CSF) derivative (KW-2228) on the growth of G-CSF-dependent hemopoietic progenitor
      cells: granulocyte precursor cells (CFU-G), leukemic blast progenitors freshly
      obtained from 9 patients with acute myeloblastic leukemia (AML) and cells of a G
      CSF-dependent human AML cell line (OCI/AML 1a). KW-2228 showed a higher
      stimulating effect than recombinant human G-CSF (rhCSF) on CFU-G; 3 out of 9
      leukemic blast progenitors and OCI/AML 1a cells. The difference in biochemical
      stability between rhG-CSF and KW-2228 was considered to explain the superior
      colony-stimulating activity of KW-2228. The results show that KW-2228 will be a
      new granulopoietic factor.

PMID- 1381544
TI  - Thyroid hormone regulation of human pituitary alpha subunit gene expression.
AB  - The thyroid hormone T3 exerts an inhibitory effect upon pre-translational
      expression of the alpha subunit gene in the anterior pituitary. In the intact
      animal oestrogen alone is without effect upon alpha gene expression but oestrogen
      modulates the influence of T3 deficiency upon the alpha gene. T3 effects upon
      alpha transcription are mediated via sequences within 98 bp of the
      transcriptional start site of the gene and similar 5' flanking sequences of the
      alpha gene mediate both T3 regulation and oestrogen modulation of T3 inhibition.
      This oestrogen effect may be mediated directly via interaction of the oestrogen
      receptor with the alpha gene thyroid hormone response element to which the
      oestrogen receptor is able to bind.

PMID- 1381545
TI  - The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway.

PMID- 1381546
TI  - Increased release of tissue plasminogen activator and its inhibitor in human
      parotid saliva upon stimulation.
AB  - Parotid saliva from 12 healthy volunteers was collected prior to and after 5 and
      25 min of stimulation at a constant flow rate of 0.25 or 1.0 ml min-1. In the
      salivary samples the concentrations of tPA (tissue-type plasminogen activator),
      PAI-1 (plasminogen activator inhibitor type-1), albumin and total protein were
      determined and the activity of amylase, tPA and PAI assessed. Presence of both
      tPA and PAI-1 antigen was demonstrated in all samples, and in unstimulated saliva
      the ratio between the activator and its inhibitor was 1:7. Upon stimulation we
      found a significantly increased concentration of PAI-1, a less pronounced
      increase in tPA concentration, unchanged amylase and total protein levels and
      significantly decreased albumin concentration. tPA activity was significantly
      reduced after prolonged stimulation which had no effect on PAI activity. In
      stimulated saliva a significant positive correlation between concentration of tPA
      and PAI-1 was demonstrated. Stimulation with citric acid had no effect on output
      of albumin which is passively filtered from blood, whereas the increase in flow
      rate corresponded to the significantly increased secretion rate of total protein
      and amylase which is secreted by gland cells. The secretion pattern of tPA and
      PAI-1 differed significantly from that of albumin in showing markedly increased
      output rate during the stimulation period, and the relative increase in output of
      PAI-1 was significantly higher than that of amylase and total protein. Thus, the
      results from this study suggest an active release of both tPA and its main
      inhibitor PAI-1 into saliva.

PMID- 1381547
TI  - The FGF family of growth factors and oncogenes.

PMID- 1381548
TI  - [An experimental model of intravitreal neovascularization in rabbits].
AB  - The author developed a consistent model of intravitreal neovascularization in the
      eyes of pigmented rabbits by incomplete posterior vitreous detachment after air
      injection followed by implantation of basic fibroblast growth factor (b-FGF; 250
      ng or 1 microgram) in the vitreous and simultaneous intravitreal injection of DL
      alpha-aminoadipic acid in physical saline solution (1 mg/kg). Newly formed
      vessels were observed in the proliferative fibrous membrane that surrounded the b
      FGF pellet. In fluorescein angiography, we observed fluorescein leakage from the
      newly formed vessels. Histologically, the newly formed vessels showed
      fenestration of endothelial cells. This method provides an easy and consistent
      model to study neovascularization.

PMID- 1381549
TI  - Long-term prognostic significance of ambulatory electrocardiographic findings in
      apparently healthy subjects greater than or equal to 60 years of age.
AB  - To determine the long-term prognostic significance of frequent or complex ectopic
      beats and ST-segment changes on 24-hour ambulatory electrocardiogram (ECG) in
      apparently healthy older subjects, 98 volunteers were followed up from the
      Baltimore Longitudinal Study of Aging who were 60 to 85 years old and free of
      cardiac disease by history, physical examination and maximal treadmill testing at
      the time of ambulatory ECG between 1978 and 1980. Over a mean follow-up period of
      10 years, coronary events developed in 14 subjects: angina pectoris in 7,
      nonfatal myocardial infarction in 3 and sudden cardiac death in 4. The incidence
      of coronary events did not differ significantly between subjects who developed
      the following arrhythmias and those who did not, respectively: greater than or
      equal to 30 supraventricular ectopic beats in any hour, 18 vs 13%; greater than
      or equal to 100 supraventricular ectopic beats in 24 hours, 20 vs 12%; paroxysmal
      atrial tachycardia, 15 vs 14%; greater than or equal to 30 ventricular ectopic
      complexes (VECs) in any hour, 17 vs 14%; greater than or equal to 100 VECs in 24
      hours, 18 vs 14%; or repetitive VECs, 20 vs 13%. The mean 24-hour heart rate (75
      +/- 8 vs 72 +/- 9 beats/min) as well as the maximal (116 +/- 20 vs 111 +/- 18
      beats/min) and minimal (51 +/- 6 vs 53 +/- 7 beats/min) heart rate also did not
      differ between the coronary event and non-event groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1381550
TI  - The prognostic significance of ventricular ectopic activity.

PMID- 1381551
TI  - Expression of galanin in rat primary sensory afferents after moxibustion to the
      skin.
AB  - We examined the effects of moxibustion on primary sensory neurons in the skin of
      rats using immunocytochemistry combined with a fluorescent retrograde tracer dye,
      fluoro gold (FG). Galanin-like immunoreactive (IR) fibers were often observed in
      the dermis of treated skin at 18 hours after moxibustion, while such fibers were
      rarely detected in untreated (control) skin. Moreover, most of galanin-IR fibers
      also displayed substance P (SP)-like immunoreactivity. About 20-30% of the dorsal
      root ganglion (DRG) neurons labeled when FG was injected intradermally into the
      moxibustion-treated skin showed galanin-like immunoreactivity, while the
      proportion of FG-labeled neurons with such immunoreactivity was less than 10% in
      control DRGs. These results show that moxibustion induced galanin expression by
      primary sensory neurons containing SP. The possible functions of this peptide are
      discussed in relation to the effects of moxibustion.

PMID- 1381552
TI  - A sacred symbol of an organ associated with birth resembling omega.
AB  - As a result of analogous thinking Birth = Creation, then the organs associated
      with birth have been projected as partaking in creation. Birth of a new life-form
      begins with reproduction of union of a pair as male-female. They depend upon
      their reproductive organs. Their external sex-organs are the first to initiate
      reproduction and both are considered auspicious. Reproduction leads to pregnancy
      of the female whose internal organ becomes the organ where the fetus grows until
      an independent life-form issues into the world. As this organ resembles the
      letter Omega of the Greek alphabet those who believe in prudery speak of it as
      the omega-shaped organ. Nevertheless, it is the place where a new life form
      develops and it is considered auspicious. Everything promoting the formation of a
      life-form is considered auspicious.

PMID- 1381553
TI  - Glycosulfatase activity of H. pylori toward human gastric mucin: effect of
      sucralfate.
AB  - Colonization of gastric mucosa by Helicobacter pylori, a bacterium implicated in
      the etiology of gastric disease, involves the cell surface sulfated
      glycosphingolipid receptors for the attachment. Evidence has also been obtained
      recently that sulfated mucus glycoproteins have the ability to interfere with
      this process. Here, we show that H. pylori displays glycosulfatase activity, and
      report the specificity of this enzyme toward gastric mucosal sulfated
      glycoproteins and glycolipids. With 35S-labeled human gastric sulfated mucin as
      substrate, the enzyme activity was identified in the extracellular material
      elaborated by the bacterium. The glycosulfatase exhibited maximum activity at pH
      5.7 in the presence of Triton X-100 and CaCl2, and gave on SDS-PAGE a protein
      band of 30 kDa. Specificity studies revealed that the enzyme effectively caused
      desulfation of N-acetylglucosamine-6-sulfate and galactose-6-sulfate present in
      carbohydrate chains of gastric mucins, as well as that of glucose-6-sulfate, a
      constituent of mucus glyceroglucolipids. However, the H. pylori glycosulfatase
      was ineffective toward galactosyl- and lactosylceramide sulfates which serve as
      receptors for this bacterium attachment and contain the sulfate ester group at C
      3 of galactose. The glycosulfatase activity toward human sulfated gastric mucin
      was inhibited by sucralfate. The inhibitory effect was proportional to the
      concentration of sucralfate up to 120 micrograms/ml, at which a 78% decrease in
      mucin desulfation occurred. The results demonstrate that H. pylori, through its
      glycosulfatase activity, affects the sulfated mucin and glyceroglucolipid content
      of the protective mucus layer, and that antiucler drug sucralfate is able to
      counteract the detrimental action of this enzyme.

PMID- 1381554
TI  - Serum trypsin in chronic renal failure and transplant patients.
AB  - The frequency and degree of elevated serum levels of trypsin (T) and correlation
      with other pancreatic enzymes were determined in several groups of patients with
      renal disease, i.e., patients with chronic renal failure (CRF), hemodialysis
      patients (HD), renal transplant recipients (RT), and in a control (C) group. Mean
      values of T were significantly higher in all other groups than in the C group (p
      less than 0.0001). A statistically significant correlation between T and
      creatininemia levels was found only for the RT group (p less than 0.0001).
      Correlations between T versus pancreatic amylase and T versus lipase activity
      were found to be statistically significant in the CRF and RT groups (p less than
      0.01), but not in the HD group. Most patients in all groups had T values higher
      than the maximum value observed in the controls and, of them, most had very
      elevated values. The results suggest that in chronic renal pathology there are
      frequent and significant increases in serum T levels, circulating in parallel
      with the other pancreatic enzymes. It is possible that, together with the renal
      excretion impairment, there could also be subclinical pancreatic damage or a
      dysfunction of the other means of elimination of T that can be responsible for,
      or contribute to, the serum increase in the enzyme.

PMID- 1381555
TI  - Persistence of colonic India ink tattoos.

PMID- 1381556
TI  - Cell-matrix adhesion receptors: relevance to glomerular pathology.

PMID- 1381557
TI  - A health survey of toll booth workers.
AB  - The prevalence of respiratory and other health problems in a cohort of highway
      toll booth workers was surveyed by mailed questionnaire. In a low proportion of
      respondents (43.2%), a high prevalence of central nervous system complaints
      (headaches, irritability, or anxiety, and unusual tiredness), mucous membrane
      irritation (eye irritation, nasal congestion, and dry throat), and
      musculoskeletal problems (joint and back pains) was found. We believe these
      symptoms are reflective of the acute irritant and central nervous system effects
      of exposure to motor vehicle exhaust. The musculoskeletal complaints are likely
      the result of bending, reaching, and leaning out of the toll booth. The need for
      in-depth evaluation of the ventilation systems and the ergonomic and job
      stressors of work at toll booths is suggested by these results.

PMID- 1381558
TI  - Detection of bone marrow metastases in small cell lung cancer patients.
      Comparison of immunologic and morphologic methods.
AB  - An immunocytochemical method, involving four monoclonal antibodies (MAbs)
      previously selected for their specific binding to small cell lung cancer (SCLC)
      cells in human bone marrow, was used for detection of bone marrow metastases in
      81 patients with diagnosed SCLC. This procedure was compared with two routine
      morphologic methods with regard to diagnostic efficiency and sensitivity. Bone
      marrow involvement was found in 26 patients (32%), one of which had limited
      disease according to conventional clinical criteria. Eight of the positive cases
      were exclusively diagnosed by immunocytochemistry, whereas the histologic and
      cytologic methods separately identified two patients each. Immunocytochemistry
      had a detection level of tumor cells in the mononuclear cell fraction of
      approximately 1-2%, whereas no patients with less than 10% immunocytologically
      detectable tumor cells were diagnosed by cytomorphologic examination of bone
      marrow aspirates. Evidence was obtained that the diagnostic efficiency of any
      method increased with the number of samples examined. Of the four MAbs used, the
      anti-NCAM antibody, MOC-1, labeled tumor cells in all immunologically positive
      patients, and in all but one of these patients all cytologically confirmed tumor
      cells were stained. The antibodies MOC-31, which recognize a cluster-2 antigen,
      and NrLu10 bound nearly all tumor cells in most cases, whereas MLuC1 only
      diagnosed tumor cells in a fraction of the patients. The results show that the
      immunocytochemical application of these antibodies is superior to morphologic
      techniques in detecting SCLC bone marrow metastases. Further use of the method
      might provide prognostically and therapeutically useful information.

PMID- 1381559
TI  - Distribution of albumin and alpha-fetoprotein mRNAs in normal, hyperplastic, and
      preneoplastic rat liver.
AB  - The nature of bile duct-like (oval) cells proliferating during chemical
      hepatocarcinogenesis has been controversial. To investigate this issue further,
      the authors compared the hepatic distribution of albumin (ALB) and alpha
      fetoprotein (AFP) mRNAs in rats in which oval cell proliferation was induced by
      feeding a choline-devoid diet containing 0.1% ethionine (CDE, a
      hepatocarcinogenic diet) with that in normal rats and in rats in which biliary
      epithelial cell hyperplasia was induced by either bile duct ligation or feeding
      alpha-naphthylisothiocyanate (ANIT). Northern blot analysis in parenchymal and
      nonparenchymal liver cells isolated from these animals demonstrated that ALB mRNA
      was present in the hepatocytes of both control and experimental animals, whereas
      this transcript was detected in nonparenchymal epithelial cells only in CDE-fed
      rats. Alpha-fetoprotein mRNA was not seen in either parenchymal or nonparenchymal
      cells isolated from normal or hyperplastic livers induced by bile duct ligation
      or ANIT feeding. In CDE-fed rats, however, both parenchymal and nonparenchymal
      cell populations displayed AFP message. In situ hybridization directly
      demonstrated nonparenchymal cell expression of both ALB and AFP transcripts in
      CDE-fed rats. Most surprisingly, ALB and AFP mRNAs were also detected by in situ
      hybridization in occasional nonparenchymal cells located in portal tracts near
      the limiting plate in normal liver, as well as under conditions associated with
      bile duct hyperplasia. Immunohistochemical studies of intermediate filament
      proteins, cytokeratin 19 (a marker of glandular epithelia), vimentin (a marker of
      mesenchymal lineage), and desmin (a marker of muscle cell differentiation)
      demonstrated that oval cells, as well as normal and hyperplastic bile duct cells,
      were positive for cytokeratin 19 and negative for both vimentin and desmin.
      Cytokeratin-positive oval cells formed duct profiles and were connected to
      preexisting ductules and ducts. These results are construed to suggest that oval
      cells proliferating during CDE hepatocarcinogenesis are derived from epithelial
      cells within the biliary tree. The presence of cells with similar morphologic
      appearance, periportal location, and AFP and ALB expression in normal liver
      suggests that these cells may be the progenitors of oval cells induced by some
      carcinogenic regimens.

PMID- 1381560
TI  - Proliferating cell nuclear antigen immunohistochemistry in rat aorta after
      balloon denudation. Comparison with thymidine and bromodeoxyuridine labeling.
AB  - The authors compared detection of proliferating vascular smooth muscle cells
      (SMC) in vitro and in vivo with proliferating cell nuclear antigen (PCNA)
      immunohistochemistry and two established methods: [3H]thymidine autoradiography
      and bromodeoxyuridine immunohistochemistry. Labeling with [3H]thymidine and
      bromodeoxyuridine of rat vascular SMC in culture stained 11% +/- 2% and 11% +/-
      1% of cells, and PCNA immunohistochemistry 22% +/- 2% of cells. Proliferation in
      the media of the denuded rat aortae was highest 3 days after denudation: 4.2%,
      3.8%, and 4.7% of labeled cells with [3H]thymidine, bromodeoxyuridine, and PCNA,
      respectively. In the intima, proliferation was highest 7 days after denudation
      with 42% [3H]thymidine, 40% bromodeoxyuridine, and 46% PCNA-positive cells. With
      double labeling, all [3H]thymidine-positive cells were PCNA positive, whereas
      some cells were only positive for PCNA. The authors conclude that PCNA
      immunohistochemistry compares favorably with [3H]thymidine autoradiography, and
      bromodeoxyuridine immunohistochemistry.

PMID- 1381561
TI  - T lymphocytes expressing HECA-452 epitope are present in cutaneous acute graft
      versus-host disease and erythema multiforme, but not in acute graft-versus-host
      disease in gut organs.
AB  - Lymphocytes in formalin-fixed skin biopsies from patients with cutaneous acute
      graft-versus-host disease (aGVHD) were studied with HECA-452 (an antibody
      recognizing lymphocytes with skin-homing properties) and a panel of antibodies
      recognizing pan-B (L26 [CD20]), pan-T (L60 [CD43] and A6 [CD45RA]), and T-helper
      subset (OPD4) antigens in paraffin sections. Biopsies from patients with erythema
      multiforme (EM) were similarly studied for comparison. In both conditions, T
      lymphocytes stained by OPD4 were predominantly confined to the dermis, whereas
      those stained by HECA-452 were concentrated in the epidermis; however, there was
      considerable variation between cases, and overlap between findings in the dermis
      and epidermis. Lymphocytes similarly studied in paraffin sections of liver,
      salivary gland, and gut affected by aGVHD were essentially unreactive with HECA
      452, although they were largely stained by pan-T markers and showed some
      comparable reactivity with OPD4. The findings suggest that aGVHD of the skin is
      mediated by a different set of lymphocytes than in gut organs, and may have a
      similar immunologic mechanism to EM.

PMID- 1381562
TI  - Assessment of proliferative activity in ovarian neoplasms by flow and static
      cytometry. Correlation with prognostic features.
AB  - We undertook a prospective flow and static cytometric study of proliferative
      activity in 74 malignant, borderline and benign ovarian neoplasms. Proliferative
      activity as assessed by S phase fraction (SPF), and immunostaining of tissue
      sections with Ki-67 antibody was compared with prognostically important
      clinicopathologic features. Malignant neoplasms had higher median percentage Ki
      67 staining (27.6%) than borderline (12.3%) and benign (2.7%) tumors (P less than
      0.05). Percentage Ki-67 staining correlated with SPF, DNA index, architectural
      grade, nucleolar grade, and mitotic count in malignant tumors; with nucleolar
      grade in benign tumors and with none of these variables in borderline tumors.
      Similarly, malignant neoplasms had a higher median SPF (11.5%) than borderline
      (3.4%) and benign (2.9%) neoplasms (P less than 0.05). In malignant neoplasms,
      SPF correlated with percentage Ki-67 staining, DNA index, age, and stage, but
      with none of these in borderline or benign neoplasms.

PMID- 1381564
TI  - Morphologic changes in basal cells during repair of tracheal epithelium.
AB  - Basal cells are differentiated with respect to junctional adhesion mechanisms and
      play a role in attachment of columnar epithelium to the basal lamina. Although
      much is known about nonciliated and ciliated cell differentiation during the
      repair process after injury, little is known about the basal cell. We studied the
      morphology of basal cells and quantitated junctional adhesion structures during
      repair of tracheal epithelium exposed to toxic cotton smoke. Ten adult ewes were
      given a smoke injury to a portion of the upper cervical trachea and were killed
      at 4, 6, 8, 10, and 18 days after injury for morphometric studies. At 4 days,
      there was a stratified reparative epithelium over the basal lamina, which was two
      to four cells in depth. The basal cells were identified by their hemidesmosome
      (HD) attachment to the basal lamina. Basal cells were about 69% larger than
      controls and flattened rather than columnar. The amount of HD attachment was 192%
      greater than controls. In contrast, volume density of cytokeratin filaments had
      decreased about 47%. Basal cells had returned to normal numbers and size and a
      columnar shape by day 18. The amount of desmosome (D) and HD attachment and
      volume density of cytokeratins had also reached control levels by day 18. These
      data indicate that morphology of basal cells changes during the initial stages of
      reparative regeneration but returns to normal by 18 days. Morphologic changes
      appear to reflect changes in size of the cell associated with cell division
      rather than differentiation of recently divided basal cells.

PMID- 1381563
TI  - Adhesion receptor profile of thymic B-cell lymphoma.
AB  - Primary thymic B-cell lymphoma is clinically characterized by aleukemic, highly
      aggressive local growth, infrequent distant metastasis, and infrequent secondary
      lymph node involvement. VLA-1 to VLA-6 are cell surface molecules binding to
      matrix molecules such as collagen, fibronectin, epiligrin, and laminin. VLA-4
      additionally binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion.
      Other molecules involved in cell/cell adhesion are LFA-1 (CD11a/CD18), Mac
      1(CD11b/CD18) and their ligand ICAM-1 (CD54), p150,95 (CD11c/CD18), LFA-3 (CD58),
      CD44, and LECAM-1. Twenty-three tumors, together with normal lymphoid tissue,
      were immunohistochemically examined to investigate the expression pattern of
      these molecules in thymic B-cell lymphomas and in their putative normal
      counterparts, namely thymic medullary B cells. Thymic B-cell lymphomas
      consistently lacked VLA-1,-2,-3,-5,-6, and CD11b, expressed ICAM-1 in 21 of 23
      cases but were heterogenous for VLA-4, LFA-1, CD11c, LFA-3, CD44, and LECAM-1.
      Presence of LFA-1 correlated with LFA-3 expression (P = 0.029). The receptor
      profile of thymic B-cell lymphoma was reminiscent of the expressional status of
      normal thymic medullary B cells in some aspects but deviated in others: Assuming
      that, in terms of differentiation, thymic B-cell lymphoma is related to the
      asteroid variant of thymic medullary B cells, a propensity to down-regulate/lose
      VLA-4, CD11a, CD44, and LECAM-1 would have to be supposed in conjunction with a
      tendency to overexpress ICAM-1 and LFA-3. Sclerosis as an inconsistent phenomenon
      in thymic B-cell lymphoma was absent in 8 of 23 tumors. Presence of sclerosis
      correlated with LECAM-1 expression of the tumor cells (P = 0.038). Recent studies
      suggest that a locally growing/aleukemic phenotype of a B-cell neoplasia might be
      determined by the phenotype VLAs-, LFA-1+, ICAM-1+, CD44-, and LECAM-1-. Our data
      corroborate this view.

PMID- 1381566
TI  - Detection and quantitation of recombinant granulocyte colony-stimulating factor
      charge isoforms: comparative analysis by cationic-exchange chromatography,
      isoelectric focusing gel electrophoresis, and peptide mapping.
AB  - Routine quantitation of recombinant human granulocyte colony-stimulating factor
      charge isoforms in the purified protein product requires development of a
      reliable analytical method. In this report, isoelectric focusing gel
      electrophoresis, peptide mapping, and cation-exchange high-performance liquid
      chromatography are compared and evaluated in the analysis of charge isomers that
      may be present in the recombinant factor. Due to a lack of sensitivity and
      reliability, isoelectric focusing gel electrophoresis and peptide mapping are not
      recommended. However, peptide mapping can distinguish aberrant peptides with
      differences in charges and provide separation for subsequent structural
      characterization. By this approach, an N-terminally blocked formylmethionyl
      species was identified to be the minor charge isoform in the purified
      preparations of recombinant human granulocyte colony-stimulating factor. In
      contrast to electrophoresis and peptide mapping, a strong cationic-exchange
      chromatographic procedure was found to be the most selective, sensitive, and
      reproducible analytical method. The sensitivity and reliability of the method
      were evaluated and validated using the formylmethionyl isoform and several
      deamidated analogs (Gln----Glu) made by site-directed mutagenesis. Recombinant
      human granulocyte colony-stimulating factor preparations contain a very low to
      undetectable level of the formylmethionine isoform and have no detectable
      deamidated isoforms.

PMID- 1381567
TI  - Substance P, thyrotropin-releasing hormone, and monoamine metabolites in
      cerebrospinal fluid in sleep apnea patients.
AB  - The cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone
      (TRH), substance P (SP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid
      (HVA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were measured in 15
      consecutive patients with the sleep apnea syndrome (SAS) and in healthy control
      subjects. Second measurements were performed 6 months after surgical treatment in
      10 of the patients. The mean (+/- SD) concentration of TRH-like immunoreactive
      material (TRH-LIM) (pg/ml) did not differ significantly between patients with SAS
      (8.1 +/- 2.8) and control subjects (7.5 +/- 2.2). However, postoperatively, this
      concentration was increased in the six clinically cured patients with SAS, from
      6.9 +/- 2.7 to 9.4 +/- 1.6 (p less than 0.03). Substance P-like immunoreactive
      material (SP-LIM) was higher in untreated patients with SAS than in control
      subjects: 19.2 +/- 6.7 versus 14.4 +/- 4.2 fmol/ml (p less than 0.02), and the
      level remained high after operation in the group treated surgically. The HVA, 5
      HIAA, and MHPG concentrations were similar in patients with SAS and control
      subjects, and no consistent changes were found postoperatively. The CSF
      deviations in TRH-LIM and SP-LIM concentrations in the patients may reflect a
      primary central nervous system defect or they may be secondary to intermittent
      nocturnal hypoxia, progressive hypercapnia, and/or sleep fragmentation. In this
      sense, both these systems may be markers of SAS-SP as a "trait" marker and TRH as
      an indicator of the current state.

PMID- 1381568
TI  - [Stem cell factor/c-kit interaction in primordial germ cell, melanoblast and
      hematopoietic progenitors].
AB  - Mutation at S1 or W loci are characterized by lacks of pigmentation,
      gametogenesis and hematopoiesis. Stem cell factor and its receptor, which is
      encoded by c-kit proto-oncogene, play an important role in the survival and
      proliferation of these primitive cells. Primordial germ cell is maintained and
      expanded on cells transfected with membrane-bound SCF gene. Pigmentation of mouse
      embryo is influenced by administration of monoclonal antibody for c-kit product,
      ACK 2, because of inhibition of melanoblast migration to epidermal tissue.
      Moreover, hematopoietic progenitors are considered to be maintained and expanded
      in liquid culture in the presence of SCF and other growth factors. All of these
      primitive cells express c-kit product and the direct action of SCF is expected.
      However, two types of SCF, soluble form and membrane-bound form, exist and the
      physiological significance of these forms in vivo remain unsolved.

PMID- 1381565
TI  - Continuous spectrophotometric assay of protein tyrosine phosphatase using
      phosphotyrosine.
AB  - A continuous activity assay for protein tyrosine phosphatases (PTPs), employing
      phosphotyrosine (P-Tyr) as a substrate, has been developed and applied to measure
      the activities of two purified enzymes, namely, the full length T-cell protein
      tyrosine phosphatase (TC PTP) and its truncated form (TC delta C11 PTP). The
      reaction was followed by changes in ultraviolet absorption and fluorescence
      resulting from the dephosphorylation of P-Tyr. Both enzymes obey Michaelis-Menten
      kinetics, with Km = 304 microM, Vmax = 62,000 units/mg for TC PTP and Km = 194
      microM, Vmax = 73,000 units/mg for TC delta C11 PTP. The D- and L-forms of P-Tyr
      are equally effective as substrates. The optimum pH for both enzymes is 4.75. The
      known effectors of PTPs have the predicted effects on catalytic activity.

PMID- 1381569
TI  - [Treatment of elderly patients with hematological malignancies].
AB  - Treatment of elderly patients with hematological malignancies is difficult and a
      matter of controversy. Low responsiveness to therapy and high risk of mortality
      have been reported. The risk of chemotherapeutic death increases after age 60,
      and an age-adjusted chemotherapy schedule is needed. In stage III and IV
      Hodgkin's disease, for example, an age-adjusted COPP regimen may be adopted. Many
      non-Hodgkin lymphomas (NHL) of elderly patients have a slow course. However, for
      intermediate to high grade aggressive NHL, dose-reduced CHOP regimen, or non- or
      low-dose methotrexate-containing programs like BECALM, CNOP, and low dose-ACOP-B
      are acceptable. MACOP-B regimen with G-CSF may be used for patients under age 65.
      For the treatment of elderly patients with AML, it is reported that a reduced
      dose DAT regimen is better than the standard dose for inducing CR in patients
      older than 60. In elderly AML patients over 60, the dose-adjustment reported by
      Mori, or low-dose cytarabine with G-CSF, is recommended. Information about
      elderly patients with acute lymphoblastic leukemia is scarce. Aggressive
      treatments like L-17 M regimen are not tolerable by elderly patients, and a
      combination chemotherapy consisting of vincristine and prednisolone is
      recommended.

PMID- 1381570
TI  - [Quality of life for older people under oncological treatment].
AB  - Recently, an argument over the medical treatment of older patients has arisen in
      the field of clinical oncology. In the past oncological treatment has been geared
      to young and middle-aged people. Currently, oncological treatment takes the
      peculiarities of older people into consideration. Firstly, it highlights the
      multidimensionality of Quality of Life (QOL) as an important element, with
      subjectivity the second element. This notion has gained a worldwide consensus.
      The domain of "multidimensionality" consists of: 1. Physical status and
      functional abilities 2. Psychological status and well-being 3. Social interaction
      4. Economic status and factors With these factors in mind, different questions
      are asked, depending on the condition of each patient, in order to let the
      patient form his/her own judgment on possible medical treatment. However, it is
      sometimes difficult for older people to make such judgments due to problems such
      as depression or their diminishing mental ability. Also, it is impossible to
      define life satisfaction indiscriminately without regard to individual outlook.
      QOL for older people is generally characterized by "individuality" which
      includes: 1) A person's integrity; 2) independence; and 3) autonomy. Though these
      elements are taken into account in adopting the above-mentioned methodology, the
      field of clinical oncology's two concepts of QOL still apply in principle.
      Flexibility to put emphasis on different elements of the domain will be
      necessary. Even though QOL for older people is a matter of subjective judgment,
      the "sound judgment of professionals" (objective and scientific judgment of
      caregivers) can be adopted in cases when there is difficulty in
      communication.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381571
TI  - [High-dose adjuvant chemotherapy with peripheral blood stem cell transplantation
      for breast cancer with poor prognosis--a pilot study].
AB  - Three patients with breast cancer with poor prognosis were treated with high-dose
      chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as
      adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with
      Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and
      Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human
      granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery
      from myelosuppression. This combination chemotherapy was given every 3 weeks for
      3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC)
      were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day,
      Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3
      consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x
      10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT
      were well tolerated, recovery from myelosuppression of the HD-CT was very quick
      and no serious side effects were observed.

PMID- 1381572
TI  - [Anticancer effect and side effect of arterial chemoembolization using cis
      diamine-dichloroplatinum (II)/4-0-tetrahydropyranyl-adriamycin-lipiodol (CTL)
      suspension on hepatocellular carcinoma].
AB  - Seventeen patients with hepatocellular carcinoma were treated by intraarterial
      injection of CTL suspension. The doses of CTL suspension, CDDP and THP(mean +/-
      SD)/injection were 4.1 +/- 1.6 ml, 81.9 +/- 31.6 mg and 13.5 +/- 5.2 mg,
      respectively. The therapy was given once in 10 patients, twice in 6 and 4 times
      in one. Over 50 per cent reduction in tumor size was obtained in 5 patients
      (30%). Fifty or more % decrease in serum alpha-feto-protein (AFP) levels was
      observed in 3 of 7 patients (43%) with the initial serum AFP level of more than
      200 ng/ml, Fever, abdominal pain, nausea and vomiting were noted in most cases.
      However, they disappeared within 2 weeks after therapy was completed. No severe
      complications were encountered except one case of a liver abscess which healed by
      administration of antibiotics. No severe changes in laboratory data were
      observed. This study suggests that a new method of intraarterial injection must
      be developed to enhance the therapeutic effect even more, in addition to an
      increased injection dose of CDDP/THP-LPD and higher concentration of CDDP and THP
      in LPD.

PMID- 1381573
TI  - Transient hypothyroxinaemia associated with developmental delay in very preterm
      infants.
AB  - In 563 surviving very preterm (less than 32 weeks gestational age) and/or very
      low birthweight (less than 1500 g) infants the relationship between neonatal
      thyroxine concentration and psychomotor development at 2 years of age (corrected
      for preterm birth) was studied. A significant association was found between low
      neonatal thyroxine concentration and a negative score on the three milestones of
      development. These findings do not support the view that transient
      hypothyroxinaemia in preterm infants is harmless.

PMID- 1381574
TI  - Children of parents in prison.

PMID- 1381575
TI  - Histamine release and morphological changes in basophilic granulocytes of atopic
      asthmatics induced by antigen, anti-IgE and Ca ionophore A 23187.
AB  - Morphological changes of basophils from atopic asthmatics were compared among
      antigen, anti-IgE and Ca ionophore A23187 stimulation. 1. Antigen induced rapid
      and marked increase of histamine release from basophils compared with Ca
      ionophore A23187. 2. The decrease in number of basophils following stimulation
      with the agents was significantly higher in antigen stimulation than in Ca
      ionophore A23187 stimulation. 3. The increased ratio of short to long axis
      diameter (L/Sb ratio) of the cells, which shows an increased motility of
      basophils, was significantly higher in antigen stimulation. The ratio did not
      change by stimulation with Ca ionophore A23187. 4. Stimulation of basophils by Ca
      ionophore A23187 induced marked increase in mean diameter (MD) of the cells.
      Activation of basophils by anti-IgE was similar to that by antigen, but slower in
      start and shorter in duration compared with antigen. The results show that an
      increase in motility is essential for release mechanism of chemical mediators
      from basophils in antigen and anti-IgE stimulation, but not in Ca ionophore
      A23187 stimulation.

PMID- 1381576
TI  - Anti-peptide antibodies reactive with epitopic domains of porcine amelogenins at
      the C-terminus.
AB  - This was an immunological investigation of the processing of porcine amelogenins
      in situ. Rabbit and rat anti-peptide sera reacted specifically with the
      hydrophilic segment of the intact amelogenins at the C-terminus. The immunogens
      used were the synthetic peptides: (a) C13 composed of PATDKTKREEVDC and (b) C25
      composed of MQSLLPDLPLEAWPATDKTKREEVD. These peptides correspond to the C
      terminal 12- and 25-residue segments of porcine amelogenin, respectively. Cystine
      was introduced at the C-terminus of C12 for KLH-binding (C13). Western blot
      analysis disclosed that: (i) both rabbit and rat anti-C13 sera reacted
      selectively with the 25-kDa porcine amelogenin and three other minor components
      (27, 22 and 18 kDa); (ii) anti-C25 peptide sera, additionally, reacted with the
      23-kDa amelogenins (a degradation derivative of the 25-kDa protein, lacking the
      12-residue segment at the C-terminus) and as trace components, 20-, 16- and 14
      kDa moieties. Importantly, all the proteins reactive with the anti-C13 serum were
      concentrated in the outer secretory enamel adjacent to the ameloblasts,
      decreasing significantly in the underlying inner secretory enamel.
      Immunohistochemical studies applying the anti-peptide sera to the developing
      tooth germs of a minipig also confirmed the localization of reactivity in the
      outer secretory region. Neither anti-peptide serum reacted with porcine non
      amelogenins, serum proteins nor dentine matrix proteins at the dilutions tested.
      however, it was found that both the anti-C13 and C25 sera reacted with human
      keratin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381577
TI  - Regulation of secretion by vasoactive intestinal peptide in isolated perfused rat
      submandibular glands.
AB  - The isolated, perfused gland was used to examine the regulation of saliva volume
      and protein content by vasoactive intestinal peptide (VIP). In the absence of
      other secretagogues, VIP produced a modest, sustained saliva flow with a biphasic
      dose-response curve in which saliva volume was greatest at 1 nM VIP (28.5 +/- 3.8
      microliters in the first 5 min, n = 4) but reduced at lower and higher
      concentrations. The protein concentration in saliva released in response to VIP
      (0.86 +/- 0.13 micrograms/microliters) was substantially higher than with 30 nM
      acetylcholine (0.06 +/- 0.02 micrograms/microliters) or 1 nM substance P (0.30 +/
      0.05 micrograms/microliters). During the first 5 min of stimulation, VIP and
      substance P were synergistic in terms of volume and protein content whereas
      inclusion of VIP did not increase acetylcholine-stimulated flow in the first 5
      min but produced a higher sustained flow over the next hour. After stimulation
      with acetylcholine, subsequent addition of VIP transiently enhanced saliva volume
      and protein content in a monophasic, dose-dependent manner with effects at 1 pM
      VIP and higher. The responses were different for VIP compared with other cAMP
      mobilizing agents and the involvement of multiple VIP receptor subtypes was
      suggested from experiments in which a VIP antagonist blocked the VIP enhancement
      of saliva volume but not the increase in protein.

PMID- 1381579
TI  - Primary nonkeratinized epithelial ('conjunctival') orbital cysts.
AB  - The types of orbital cysts that are most familiar to ophthalmologists are
      epidermoid and dermoid cysts, both of which are lined by keratinized stratified
      squamous epithelium. We studied six patients who had orbital cysts lined by
      nonkeratinized epithelium that resembled normal conjunctiva. Compared with
      epidermoid and dermoid cysts, these primary nonkeratinized cysts tend to cause
      symptoms later in life, occur preferentially in the superonasal aspect of the
      orbit, and are less likely to be associated with underlying bony changes.

PMID- 1381578
TI  - Immunofluorescent lectin binding patterns and glycoprotein co-localization in the
      developing murine molar tooth.
AB  - Fluorescein-conjugated lectins were used in conjunction with antibodies to
      laminin, tenascin and amelogenin to investigate saccharide expression in the
      developing tooth germ. At the bud stage, peanut agglutinin (PNA) binding
      demonstrated residues that may be D-galactose-(beta 1----3)DGalNAc, and this
      staining occurred after the expression of tenascin. Only the cap-stage enamel
      organ suprabasal cells and the enamel knot stained intensely with Ulex europeus
      agglutinin-I, but not Lotus tetragonolobus agglutinin, implying the transient
      presence of blood group H type I oligosaccharides. At the late stages of
      amelogenesis, enamel synthesis is preceded by en bloc loss of inner enamel
      basement membrane components. Before this, Bandeiraea (Griffonia) simplicifolia-
      I (BSL-I) staining was lost from postmitotic ameloblasts, suggesting that a
      glycosylated species is initially removed. Additionally, PNA was co-localized
      with amelogenin protein, suggesting that it may express beta-D-galactosyl
      sequences. These results indicate that the glycosylation patterns of matrix
      components during odontogenesis may be important as they vary in a manner similar
      to that of the well-known glycoproteins.

PMID- 1381580
TI  - Visual symptoms associated with choroidal neovascularization. Photopsias and the
      Charles Bonnet syndrome.
AB  - One hundred consecutive patients with macular choroidal neovascularization were
      studied in a cross-sectional fashion. Evidence of bilateral choroidal
      neovascularization was present in 31 patients. Among the 100 subjects, 59%
      related a history of seeing flickering or flashing lights (photopsias) in the
      affected eye or eyes. The colors varied, but in 59% of instances the lights were
      white. Twelve subjects experienced formed hallucinations (Charles Bonnet
      syndrome); in nine (75%) of these patients, the sequelae of choroidal
      neovascularization were bilateral. Symptoms that are commonly attributed to
      vitreoretinal tractional phenomena as well as neurologic and/or psychiatric
      disease are also frequently encountered in patients with macular degeneration
      associated with choroidal neovascularization.

PMID- 1381581
TI  - Recovery of mitochondrial DNA from blood leukocytes using detergent lysis.
AB  - Mitochondrial DNA (mtDNA) was isolated from leukocytes contained in whole blood
      of cattle. Leukocyte membranes except the nuclear envelope were solubilized in a
      buffer that contained 1% Triton X-100. After sedimentation of cell nuclei, mtDNA
      was purified from the cell lysate by organic solvent extraction and ethanol
      precipitation. Approximately 5 micrograms of mtDNA was recovered from 400 ml of
      whole blood, a quantity sufficient for routine DNA cloning procedures or for
      detailed restriction mapping studies. mtDNA isolated with this method is a
      suitable substrate for several DNA-modifying enzymes. Thus, preparation of mtDNA
      from blood by detergent lysis provides a noninvasive alternative to tissue biopsy
      for characterization of mitochondrial genotypes in studies of evolutionary
      genetics and population dynamics.

PMID- 1381582
TI  - Nucleotide sequence and expression of a cDNA encoding rabbit liver cytosolic
      serine hydroxymethyltransferase.
AB  - A rabbit liver cDNA library in phage lambda gt10 was screened using a portion of
      the coding sequences for rabbit cytosolic serine hydroxymethyltransferase (amino
      acids 244-420) that had been amplified by PCR, with total rabbit liver RNA as a
      template. A clone of 2.3 kb (pUS1203) was isolated and the nucleotide sequence
      showed that it contained an open reading frame of 1452 bp, which coded for serine
      hydroxymethyltransferase and was flanked by 155 bp at the 5' end and 653 bp at
      the 3' end. The full-length cDNA was cloned into an expression vector and
      transfected into COS-1 cells. Serine hydroxymethyltransferase activity was
      increased by 33% in the transfected cells and a new protein band of the
      appropriate size was seen by SDS/PAGE analysis of proteins extracted from
      transfected cells. The protein sequence for rabbit cytosolic serine
      hydroxymethyltransferase derived from the cDNA nucleotide sequence was compared
      with three other derived or known prokaryotic and eukaryotic sequences. An
      overall sequence similarity of 34% was noted between all four sequences, whereas
      the similarity between the rabbit cytosolic and mitochondrial isoforms was 62%.

PMID- 1381583
TI  - Age-dependent decrease in the amount of eukaryotic initiation factor 2 in various
      rat tissues.
AB  - Recent studies have suggested that the decline in protein synthesis that occurs
      in rat liver and brain during development and aging is associated with a decrease
      in the activity of eukaryotic initiation factor 2 (eIF-2). One way in which eIF-2
      activity could be decreased in tissue extracts would be through a decrease in the
      activity of the GDP exchange factor, eIF-2B. In the present study, the activity
      of eIF-2B was measured in tissue extracts and was found to be less in older than
      in younger rats. Thus a decrease in eIF-2B activity could account for part of the
      decrease in protein synthesis that occurs during aging. Another way in which eIF
      2 activity could be decreased would be through a decrease in amount of the
      protein. Therefore the amount of eIF-2 in various tissues was quantified by
      protein immunoblot analysis. We found that the amount of eIF-2 relative to total
      protein tended to fall with increasing age. Furthermore, eIF-2 content was
      directly proportional to the rate of protein synthesis in the tissues examined.
      Finally, slot-blot analysis of polyadenylated RNA revealed no significant change
      in the relative abundance of eIF-2 alpha mRNA with age. The last-mentioned
      experiments suggest that the synthesis of eIF-2 may be regulated through changes
      in the deficiency of translation of eIF-2 alpha mRNA rather than through changes
      in gene transcription.

PMID- 1381584
TI  - Structure and expression of the Drosophila ubiquitin-52-amino-acid fusion-protein
      gene.
AB  - Ubiquitin belongs to a multigene family. In Drosophila two members of this family
      have been previously described. We report here the organization and expression of
      a third member, the DUb52 gene, isolated by screening a Drosophila melanogaster
      genomic library. This gene encodes an ubiquitin monomer fused to a 52-amino acid
      extension protein. There are no introns interrupting the coding sequence.
      Recently, it has been described that this extension encodes a ribosomal protein
      in Saccharomyces, Dictyostelium, and Arabidopsis. The present results show that
      the 5' regulatory region of DUb52 shares common features with the ribosomal
      protein genes of Drosophila, Xenopus and mouse, including GC- and pyrimidine-rich
      regions. Moreover, sequences similar to the consensus Ribo-box in Neurospora
      crassa have been identified. Furthermore, a sequence has been found that is
      similar to the binding site for the TFIIIA distal element factor from Xenopus
      laevis. The DUb52 gene is transcribed to a 0.9 kb mRNA that is expressed
      constitutively throughout development and is particularly abundant in ovaries. In
      addition, the DUb52 gene has been found to be preferentially transcribed in
      exponentially growing Drosophila cells.

PMID- 1381585
TI  - Lipoprotein (a) promotes plasmin inhibition by alpha 2-antiplasmin.
AB  - Plasmin inhibition by alpha 2-antiplasmin (alpha 2AP) is regulated by the
      vascular components fibrin(ogen) fragments, plasminogen and lipoprotein (a).
      Kinetic analysis demonstrates that CNBr-derived fibrinogen fragments completely
      protect plasmin from alpha 2AP. Plasminogen and 6-aminohexanoic acid decrease the
      rate of inhibition by 5- and 10-fold respectively. These studies show that CNBr
      derived fibrinogen fragments and 6-aminohexanoic acid bind plasmin kringle(s)
      with binding constants of 2 micrograms/ml and 120 microM respectively, and that
      plasminogen binds to alpha 2AP with an affinity of 0.5 nM. The unmodulated
      inhibition is not effected by the presence of lipoprotein (a), but in the
      presence of protective CNBr-derived fibrinogen fragments the rate of inhibition
      is increased by the presence of the lipoprotein. The kinetics demonstrate that
      lipoprotein (a) binds to CNBr-derived fibrinogen fragments with an affinity of 4
      nM, displacing plasmin from the protective surface. In addition, tissue-type
      plasminogen activator and trypsin inhibition by alpha 2AP is not slowed by the
      presence of CNBr-derived fibrinogen fragments or plasminogen (Pg), respectively.
      These kinetics suggest that the initial reversible interaction between plasmin
      and alpha 2AP is mediated by binding of the inhibitor to the kringle 1 domain of
      plasmin, with a reversible inhibition constant (Ki) of 5.0 x 10(-10) M. Under
      conditions where this kringle-inhibitor interaction is blocked, the reversible
      inhibition still occurs between the plasmin and alpha 2AP, but the initial Ki is
      increased to 5.0 x 10(-9) M. These data suggest that, in the circulation, plasmin
      inhibition by alpha 2AP may be down-regulated by fibrin, fibrin(ogen) fragments
      and Pg, but up-regulated by lipoprotein (a) in the presence of fibrin or
      fibrin(ogen) fragments. The lipoprotein (a)-mediated promotion of plasmin
      inhibition may provide an additional mechanism by which the lipoprotein impairs
      fibrinolysis and promotes atherosclerosis.

PMID- 1381586
TI  - Effects of Taxotere on murine and human tumor cell lines.
AB  - Taxotere (RP 56976, NSC 628503), an analog of taxol, is an inhibitor of
      depolymerisation of microtubules and is currently in Phase I clinical trials.
      Comparisons of the cytotoxicities of Taxotere and taxol have been studied on
      several murine (P388, SVras) and human cell lines (Calc18, HCT116, T24, N417,
      KB). Taxotere was found more potent than taxol (1.3-12 fold), a result which
      could be explained by its higher affinity than taxol for microtubules. In
      agreement with its postulated mechanism of action, Taxotere is more cytotoxic on
      proliferating than on non proliferating N417 cells and does not inhibit cellular
      DNA, RNA and protein synthesis. Taxotere gives partial cross resistance on P
      glycoprotein resistant P388/DOX cell line, in contrast to taxol which gives a
      complete cross resistance. On the other hand, no cross resistances were observed
      on Calc18/AM and P388/CPT5 cell lines, bearing modified activities of
      topoisomerase II and topoisomerase I, respectively. These results underline the
      higher cytotoxic activity of Taxotere compared to taxol, and the lack of cross
      resistance of that class of agent with the topoisomerase I and II-related
      multidrug resistance phenotypes.

PMID- 1381587
TI  - CD11b is a calcium-dependent epitope in human neutrophils.
AB  - Human neutrophils expressing complement receptor 3 (CR3) were treated with
      various concentrations (0.04-10 mM) of Ca2+/Mg(2+)-chelating agent EDTA and the
      expression of CD11b, the CR3 alpha chain antigenic epitope, was examined using
      monoclonal antibodies and flow cytometry. EDTA caused a dose-dependent decrease
      in the reactivity of two anti-CD11b monoclonal antibodies, Leu15 and IOM1. The
      reduced expression of CD11b in EDTA-treated cells was partly restored by the
      addition of Ca2+ ions whereas the addition of Mg2+ ions had no effect on CD11b
      level. The expression of the CR3 beta chain epitope, CD18, was markedly decreased
      only by 10 mM EDTA. These results suggest that the CD11b epitope may be
      associated with the Ca(2+)-binding domains of CR3 alpha chain and its recognition
      by antibodies depends on the presence of bound Ca2+.

PMID- 1381588
TI  - Ozonation of lysozyme in the presence of oleate in reverse micelles of sodium di
      2-ethylhexylsulfosuccinate.
AB  - Ozone is shown to react with lysozyme in reverse micelles formed by 0.1 M sodium
      di-2-ethylhexylsulfosuccinate and 1.2-3 M water (pH 7.4) in isooctane solvent.
      The reaction of ozone is assessed by the oxidation of tryptophan residues in the
      protein to N-formylkynurenine. Cosolubilization of oleate in lysozyme-containing
      reverse micellar solutions at concentrations of 0.5-10 mM results in a
      progressive inhibition (19% to 82%) of the oxidation of tryptophan residues with
      a concentration for 50% inhibition around 2 mM. At this concentration of oleate,
      the magnitude of inhibition is independent of the micelle size and concentration,
      the overall interfacial area of reverse micelles, and the amount of ozone
      employed. These findings are discussed in terms of competitive reactions of ozone
      with unsaturated fatty acids and proteins in the lung lining fluid and in
      biological membranes.

PMID- 1381589
TI  - The sulfhydryl reagent N-ethylmaleimide induces hyperphosphorylation on tyrosine
      residues in the Jurkat T-cell line.
AB  - Tyrosine protein kinases have been shown to be functionally involved in
      regulation of cellular signalling, proliferation and transformation. The activity
      of tyrosine protein kinases is counterbalanced by phospho tyrosine phosphatases
      that maintain constitutively low levels of protein phosphotyrosine in most cells.
      In this study the effect of N-ethylmaleimide on the protein tyrosine
      phosphorylation was tested in Jurkat T-cells. Treatment of intact cells for 5-10
      mins with 50-100 microM N-ethylmaleimide resulted in a dramatic increase in
      phosphorylation on tyrosine residues. Phosphoaminoacid analysis revealed an up to
      ten-fold increase in the content of phosphotyrosine. N-ethylmaleimide blocked the
      phospho tyrosine phosphatases activity of immunoprecipitated CD45 while in a
      kinase assay N-ethylmaleimide did not affect the 32P-gamma-ATP phosphorylation of
      substrates. The N-ethylmaleimide-induced hyperphosphorylation was reversed by
      treatment with 2 mM dithiotreitol. It is concluded that N-ethylmaleimide offers a
      novel useful tool for identification of substrates for tyrosine protein kinases
      and for studies on phosphotyrosine-dependent protein interactions.

PMID- 1381590
TI  - CSF monoamine metabolites in old age dementias.
AB  - Cerebrospinal Fluid (CSF) levels of the main metabolites of monoamines (MHPG, 5
      HIAA, and HVA) were measured in patients with early onset (AD) and late-onset
      (SDAT) Alzheimer's disease, vascular dementia (VD), and elderly controls.
      Psychobehavioral assessment was carried out by means of MMSE and GBS. Mean MHPG
      levels did not differ from controls; 5-HIAA was lower in VD when compared to both
      controls and SDAT. HVA was decreased in AD, SDAT, and VD with respect to
      controls. Significant correlations between HVA and psycho-behavioral parameters
      were observed in SDAT and VD groups, whereas no relationship was documented in
      AD. The SDAT group was divided in SDAT-A (age at onset: greater than 65 less than
      or equal to 80 yr) and SDAT-B (age at onset: greater than 80 yr). SDAT-A had
      significantly lower CSF HVA values than SDAT-B (165 +/- 64 vs 235.7 +/- 85). SDAT
      B HVA levels were similar to those observed in controls. Correlation analysis
      between HVA and neuropsychological variables was significant in SDAT-A, but not
      in SDAT-B. These results might support the evidence of SDAT heterogeneity.

PMID- 1381591
TI  - Synthesis of hydrolytic enzymes during production of tylosin by Streptomyces
      fradiae.
AB  - The exposure of a wild-type tylosin producing strain of Streptomyces fradiae to
      mutagenic agents resulted in the isolation of several tylosin over-producing
      strains. Examination of three mutants, T4310, 612 and 3204 showed that improved
      tylosin production was associated with increased hydrolytic enzyme activity and
      cell growth. The wild-type strain showed lower levels of hydrolytic activity
      including, protease, amylase, lipase and esterase activities and attained a lower
      cell density than the mutants.

PMID- 1381592
TI  - How sweet it is: selectin-mediating drugs.

PMID- 1381593
TI  - In situ hybridization: a valuable tool in diagnostic pathology.
AB  - In situ hybridization or hybridohistochemistry has evolved in recent years in a
      new histologic modality. In situ hybridization (ISH) can be used for the
      detection of DNA (DISH) or RNA (RISH). The potential diagnostic value within a
      pathologic setting are well recognized. In this review paper, we summarize the
      use of DISH in a pathologic setting for the detection of chromosomal aberrations
      and localization of DNA-viruses like cytomegalovirus and Epstein Barr virus. RISH
      which is still in a more experimental stage can be applied for the localization
      of RNA-virus, like human immunodeficiency virus. However, the most important
      application of RISH will be the detection of gene-expression at the level of
      mRNA. Potentially this has many applications especially in early diagnostics of
      neoplastic tissues. Finally, we have summarized some pitfalls which may hamper
      the introduction of in situ hybridization for diagnostic purposes and some future
      developments in ISH.

PMID- 1381594
TI  - Participation of lipopolysaccharide-binding protein in lipopolysaccharide
      dependent macrophage activation.
AB  - Only recently has the mechanism for lipopolysaccharide (LPS) recognition by
      macrophages been elucidated. In contrast to many ligand receptor interactions,
      the interaction of LPS with its receptor, CD14, on myeloid cells is greatly
      enhanced by prior complexation of LPS with LPS-binding protein (LBP), a recently
      discovered plasma glycoprotein. LBP is found in normal serum or plasma in the 5
      to 10 micrograms/ml range. In plasma, it reacts rapidly but transiently with LPS.
      LPS-LBP complexes then react with CD14 bearing cells. Blocking CD14 with
      monoclonal antibodies or removal of LBP from plasma blocks the ability of the
      cells to react with LPS-LBP complexes and also blocks release of cytokines and
      other mediators from the cells. In the normal lung, bronchoalveolar lavage fluid
      contains low levels of LBP. However, during acute lung injury, LBP levels may
      rise by transudation and enhance activation of alveolar macrophages to release
      injurious mediators. Description of this pathway for LPS recognition by
      macrophages and other leukocytes offers the possibility of developing new
      reagents to block LPS recognition and prevent the development of endotoxemia.

PMID- 1381595
TI  - Altered adhesion molecule expression and endothelial cell activation accompany
      the recruitment of human granulocytes to the lung after segmental antigen
      challenge.
AB  - Mounting evidence suggests that inflammatory cells recruited to the lung can
      contribute to the pathogenesis of asthma. The factors governing the activation
      and recruitment of circulating cells to the lung remain unknown, but an early
      step in this process is the interaction of adhesion molecules on circulating
      cells with those on endothelial cells. We used a segmental antigen challenge
      model followed 18 h later by bronchoalveolar lavage (BAL) to study granulocyte
      recruitment to the lung in 14 allergic subjects. Using immunofluorescence and
      flow cytometry, we determined the expression of the adhesion molecules CD11b, L
      selectin (LECAM-1), and VLA-4 on BAL and peripheral blood granulocytes. Total
      cell count and percentages of recovered eosinophils and basophils were
      significantly increased in BAL fluids from antigen-challenged segments. Compared
      with their peripheral blood counterparts, CD11b expression was increased 2- to 3
      fold on BAL eosinophils, basophils, and neutrophils (n = 9, P less than 0.05). In
      contrast, L-selectin expression was significantly decreased on BAL cells (n = 3
      to 4, P less than 0.05). Similar phenotypic changes were observed on all three
      cell types, and on neutrophils recovered from saline-challenged control lung
      segments. In two subjects, VLA-4 alpha (CD49d) expression on BAL eosinophils was
      78 +/- 5% of that seen on peripheral blood eosinophils. Because ELAM-1
      (endothelial leukocyte adhesion molecule-1, E-selectin) expression occurs during
      allergic inflammation and is shed after endothelial activation, we used a
      sensitive enzyme-linked immunosorbent assay to analyze BAL supernatants for a
      soluble form of this molecule (sELAM-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381596
TI  - Carbohydrate changes in colon carcinoma.
AB  - The colonic epithelium preferentially expresses only certain types of
      carbohydrate antigens. The most prevalent ones are the lacto-series type 1 (Gal
      beta 1,3GlcNAc) and type 2 (Gal beta 1,4GlcNAc) chain blood group-related
      substances, which can reside on both glycolipids and glycoproteins, and mucin
      type O-linked structures such as Tn, T, and sialosyl-Tn, which reside exclusively
      on glycoproteins. This review focuses on the tissue expression in the colon of
      those carbohydrate tumour-associated antigens which have been most extensively
      studied and for which the epitope structure has been defined.

PMID- 1381597
TI  - Cell surface carbohydrate in cell adhesion. Sperm cells and leukocytes bind to
      their target cells through specific oligosaccharide ligands.
AB  - During the past few years it has become increasingly evident that specific
      oligosaccharides in glycoproteins/glycolipids may play a central role in
      mammalian cell adhesion. This review deals with two of the best studied systems,
      the interaction of sperm cells with the Zona pellucida layer surrounding
      mammalian eggs, and the binding of leukocytes to endothelial cells. In the sperm
      cell-Zona pellucida system, it is known that a specific oligosaccharide(s) in the
      Zona pellucida glycoprotein 3 is responsible for binding. In the leukocyte
      endothelial cell interaction, sialyl Le(x), sialyl Le(a), sulfatides, and other
      less well-defined sugar structures are involved in cellular binding.
      Oligosaccharides involved in these adhesion events may turn out to have
      clinically important applications.

PMID- 1381598
TI  - Glycosylation of neural cell adhesion molecules of the immunoglobulin
      superfamily.
AB  - Cell adhesion molecules (CAMs) are believed to play key roles during
      morphogenesis. In this review we focus on neural CAMs belonging to the
      immunoglobulin superfamily. Data concerning distribution, expression pattern,
      structure and function of these CAMs are accumulating these years. In general,
      little is known about the importance of glycosylation for the function of these
      CAMs. The neural cell adhesion molecule, NCAM, is probably the best described
      CAM, and this molecule exhibits special carbohydrate characteristics, e.g. NCAM
      is polysialylated. Glycosylation of NCAM seems to be regulated during development
      and to influence the adhesive function of the molecule. Structure, function and
      glycosylation of NCAM are described in detail.

PMID- 1381599
TI  - Selective inhibition of HIV replication by adriamycin in macrophages but not in
      lymphocytes.
AB  - Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV
      related cancers. Due to its effect on DNA metabolism, ADR might be able to
      modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially
      less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy
      of ADR against HIV replication in both lymphocytes and M/M. We further
      investigated the mechanism(s) of action of ADR and its potential synergistic
      activity with zidovudine (AZT) or alpha-interferon (IFN alpha). ADR consistently
      inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005
      micrograms/ml ADR, while greater 90% viral inhibition was obtained with 0.05
      micrograms/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5
      micrograms/ml. No anti-HIV activity was shown by ADR in lymphocytes at
      concentrations up to 0.05 micrograms/ml, that is also the toxic dose 50% (TCID50
      for these cells). ADR neither inactivates HIV virions nor affects HIV binding
      with CD4 receptors. No inhibition of HIV reverse transcriptase by ADR was found
      at concentrations at least 2,000-fold greater than the 50% HIV inhibitory
      concentration in M/M. Molecular analysis by polymerase chain reaction (PCR)
      suggests that ADR substantially affects virus DNA production at concentrations
      that inhibit viral replication. Finally, late stages of HIV replication were not
      affected by ADR. At least additive effects of the association ADR + AZT and ADR +
      IFN alpha were obtained against de novo HIV infection of M/M.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1381601
TI  - [A patient with epilepsy presenting developmental regression after seizures-
      consideration of the mechanism from the findings of CT-scan and SPECT].
AB  - We report a 6-month-old female infant with frequent brief seizures who
      subsequently showed developmental regression. CT-scans right after her seizures
      revealed enlargement of bilateral subdural space more on the right side with an
      evidence to suggest destruction of the blood brain barrier in enhanced CT-scan,
      CT-scan, one month after the onset, showed diffuse brain atrophy. 123I-SPECT,
      which was performed 11 days after cessation of her seizures, still showed diffuse
      hypoperfusion predominantly in the right temporal area, and it returned to normal
      3 months after the onset. We discussed the mechanisms of developmental regression
      in this case from the neuroradiological findings.

PMID- 1381600
TI  - Human immunodeficiency virus replication: modulation by cellular levels of cAMP.
AB  - HIV infection is associated with qualitative and functional immune deficiencies.
      It has been shown that the in vitro infection of CD4+ cells with HIV was
      associated with sustained elevation of cAMP and cGMP. In the present report the
      role of cAMP on HIV replication in MT-4 cells was investigated. The MT-4 cells
      were infected with HIV (strain 3b), in the presence or absence of agents that
      increase intracellular levels of cAMP, through different mechanisms. At selected
      times postinfection, HIV replication was measured by reverse transcriptase
      activity or HIV P24Ag in culture supernatants. Forskolin (FK, an activator of
      adenylate cyclase 1-100 microM), Isobutyl-methylxanthine (IBMX, a
      phosphodiesterase inhibitor, which indirectly increases intracellular levels of
      cAMP, 30-100 microM) and dibutyryl (db) cAMP (0.1-10 microM) enhanced HIV
      replication, in a dose-dependent manner. FK, IBMX, and db cAMP enhanced HIV
      replication by 2- to 10-fold, 4- to 7-fold, and 2- to 6-fold, respectively.
      Intracellular levels of cAMP were measured by radioimmunoassay and were also
      enhanced. Since cAMP exerts its catalytic effects through activation of protein
      kinase (PK) A the effect of H-8 (a specific inhibitor of the cAMP dependent PK A)
      on HIV replication was simultaneously examined. The H8 at doses of 0.1 to 10
      microns inhibited HIV replication by 25 to 99.9%. Moreover H9 inhibited HIV
      replication in peripheral blood mononuclear cells by more than 90%. The
      replication of HIV appears to be a cAMP-dependent event, and PK A could possibly
      be a target for the development of anti-HIV therapies.

PMID- 1381602
TI  - 12-O-tetradecanoylphorbol 13-acetate induced differentiation in human lung
      squamous carcinoma cells.
AB  - Three human lung squamous carcinoma cell lines (NX002, CX140 and CX143)
      demonstrate features of squamous differentiation including involucrin synthesis
      and competence to form cornified envelopes. 12-O-Tetradecanoylphorbol 13-acetate
      inhibits growth of these cell lines and this growth inhibition is associated with
      enhanced differentiation.

PMID- 1381603
TI  - Control of H-2 expression in transformed nonhaemopoietic cells by autocrine
      interferon.
AB  - The relationship between autocrine interferon (IFN) production and the expression
      of class I Major Histocompatibility Complex (MHC) membrane glycoproteins in vitro
      was investigated in a panel of murine transformed cells of nonhaemopoietic
      origin. The panel included 11 cell lines of H-2Kb haplotype derived from
      fibrosarcomas, carcinomas and melanoma, and from transformed fibroblasts. IFN
      activity was detected in the conditioned medium of nine cell lines; fibrosarcomas
      were among the high IFN producers, while the non-producers were a melanoma clone
      and a lung carcinoma cell line. A significant correlation was found between IFN
      production and the expression of H-2K/D glycoproteins, thus suggesting that long
      term maintainment of MHC glycoprotein expression in vitro could be mediated by
      self produced IFN. Two IFN producer cell lines, MN/MCA1 and R80/17, were cultured
      in the presence of a blocking antiserum against IFN-alpha/beta: a significant
      decrease in H-2b expression was observed, thus indicating the existence of an
      autocrine IFN circuit. Taken together these findings suggest that release of IFN
      is a frequent event among transformed nonhaemopoietic cells, and that self
      produced IFN contributes to the regulation of MHC antigen levels in solid
      tumours.

PMID- 1381604
TI  - Antibodies for denatured human H-ferritin stain only reticuloendothelial cells
      within the bone marrow.
AB  - Human H-ferritin homopolymer was denatured in sodium dodecyl sulphate and
      injected in mice to obtain antibodies for dissociated H-subunit. The antisera and
      Moabs obtained were specific for the denatured H-chain with no cross-reactivity
      with assembled ferritins in immunoblotting experiments. In contrast the Moabs for
      native recombinant H-ferritin are specific for the assembled ferritin molecules
      with weak cross-reactivity with the denatured H-subunits. The epitope recognized
      by one of the anti-denatured H-chain Moabs was mapped on the C-terminal helix of
      ferritin. The antibodies were used to study H-ferritin conformation in cells. In
      immunocytochemistry experiments the antibodies for denatured H-ferritin stained
      HeLa and K562 cells weakly, with a different intensity and pattern to those
      obtained with anti-native H-ferritin antibody. In human bone marrow smears the
      anti-denatured ferritin antibodies stained only reticuloendothelial cells, and
      did not recognize the H-ferritin rich immature erythroblasts. It is concluded
      that assembled and denatured H-ferritins are immunogenically distinct, and that
      erythroid and reticuloendothelial cells within the bone marrow contain H-ferritin
      in different conformations.

PMID- 1381605
TI  - Use of recombinant human granulocyte colony stimulating factor in reticular
      dysgenesis.

PMID- 1381606
TI  - Amylase production in monoclonal gammopathy of undetermined significance.

PMID- 1381607
TI  - Peroxidase positive CD7+ myeloid leukaemia expressing only T lymphoid cell
      membrane markers: a new entity.

PMID- 1381608
TI  - Surface marker expression in acute myeloid leukaemia at first relapse.
AB  - Surface markers were studied at first relapse in 66 cases of acute myeloid
      leukaemia (AML), using a panel of five monoclonal antibodies directed to CD13,
      CD14, CD15, CD33 and CD34 antigens. At time of relapse, there was increased
      expression of CD33 (P = 0.002) and CD34 (P = 0.0001), and decreased expression of
      CD13 (P = 0.004) and CD15 (P = 0.0001) antigens by comparison to initial
      diagnosis. There was no strict correlation with the FAB classification. However,
      CD13 and CD33 expression changes preferentially affected granulocytic leukaemias.
      At relapse, CD14 and CD34 were significantly more expressed in monocytic than in
      granulocytic AML (P = 0.01 and 0.003 respectively). In a multivariate analysis,
      CD34 expression was associated with a low CR rate (P = 0.001) and short survival
      (P = 0.05), whereas CD15 expression was associated with long survival (P =
      0.0004). These results suggest that AML tends to relapse with a less
      differentiated phenotype than observed at diagnosis and that AML with less
      differentiated phenotype is of poor prognosis after first relapse, as also
      observed at diagnosis.

PMID- 1381609
TI  - Conserved natural humoral immunity to thyroglobulin in patients with multiple
      myeloma.
AB  - We studied humoral immunity to human thyroglobulin (hTg) during the course of
      multiple myeloma (MM). In this report, we describe the anti-hTg antibody activity
      in the sera of patients with MM. Among 63 sera tested, 28 (44%) had IgG anti-hTg
      autoantibodies (aAb), 16 (25%) exhibited IgM aAb, and six (9%) had IgA anti-hTg
      aAb. For the majority of sera the anti-hTg autoantibody activity was associated
      with more than one immunoglobulin class. IgG anti-hTg antibodies were observed in
      9/11 patients with IgA MM and in 19/40 patients with IgG MM. The IgM anti-hTG
      antibody activity was found in the sera of 11 patients with IgG MM. These results
      show that the anti-hTg activity in these patients is associated with residual
      polyclonal immunoglobulins. However, in the serum of one patient presenting a
      double monoclonal gammopathy (IgG and IgA lambda MM), the anti-hTg activity was
      carried by both the IgG lambda and the IgA lambda molecules, suggesting that in
      this case the activity was due to the monoclonal immunoglobulin itself. We also
      studied the epitopic specificity pattern of all these anti-hTg aAb. Only three
      sera recognized one antigenic region on hTg, suggesting that the majority of the
      anti-hTg aAb in MM patients were directed against antigenic regions other than
      those recognized by our panel of murine mAb. In conclusion, our results
      demonstrated that humoral immunity to hTg is maintained in MM patients. These
      data contrast with the well-documented suppression of immunity to foreign,
      especially bacterial, antigens described in MM.

PMID- 1381610
TI  - Normal aggregations of glycoprotein IV (CD36)-deficient platelets from seven
      healthy Japanese donors.
AB  - Since glycoprotein IV (GPIV) has been shown to play an important role in the
      interaction of platelets with collagen and thrombospondin, the aggregation and
      secretion of GPIV-deficient platelets were examined. Using a binding assay with
      monoclonal 125I-OKM5 antibody against CD36 antigen and crossed
      immunoelectrophoresis of the solubilized platelets against anti-GPIV antibody,
      the platelets from seven (4.1%) out of 170 healthy Japanese donors were found to
      be deficient in GPIV. The GPIV-deficient platelets showed normal aggregations in
      response to collagen as well as ADP, epinephrine, arachidonic acid and thrombin
      in comparison with GPIV-positive platelets. Polyclonal anti-GPIV antibody
      aggregated GPIV-positive platelets but not the GPIV-negative ones. The F(ab')2
      fragments of the anti-GPIV antibody competitively inhibited the anti-GPIV-induced
      aggregation, but did not affect the collagen-induced aggregation of GPIV-positive
      platelets. These results suggest that the deficiency of GPIV does not affect
      platelet aggregability.

PMID- 1381612
TI  - Quantitation of physical-chemical properties of the aqueous phase inside the phoE
      ionic channel.
AB  - The anion-specific channel of the phoE porine is a miniature body of water
      surrounded by peptide walls. The physical and chemical properties of the water in
      such a microscopic space were measured by monitoring the dynamics of a well
      studied reaction--the protolytic dissociation of a strong acid. To attain this
      purpose, we allowed pyranine (8-hydroxypyrene-1,3,6-trisulfonate) to bind to the
      anion-specific channel. The dye is bound, with a 1:1 stoichiometry, with a delta
      G = -9.5 kcal/mol. Photoexcitation of the dye, to its first electronic singlet
      state (phi OH*), renders it very acidic and the hydroxyl proton dissociates to H+
      and excited anion (phi O*-). We employed single photon-counting time-resolved
      fluorimetry, to monitor the reversible dissociation of pyranine as it proceeds
      within the channel and reconstructed the observed signal by a numerical
      integration of the differential diffusion equation pertinent for a proton within
      the channel. The most characteristic feature of the water-filled channel, is the
      intensified electrostatic interactions attained by the low dielectric constant of
      the diffusion space, epsilon eff = 24. For this reason, the electric field of a
      few positive charges is sufficient to ensure that an anion entering the channel
      will be effectively sucked in. The interaction of the water molecules with the
      peptide structure forming the channel affects the physical properties of the
      water. Their capacity to conduct proton, quantitated by the protons diffusion
      coefficient (4.5.10(-5) cm2/s), is reduced by 50% with respect to that of bulk
      water. The activity of the water in the channel is reduced to alpha H2O = 0.966.
      These observation are in accord with our previous studies of water in small
      defined cavities in proteins.

PMID- 1381611
TI  - Effects of arotinolol on exercise capacity and humoral factors during exercise in
      normal subjects.
AB  - A placebo-controlled, double-blind crossover study was undertaken in 10 normal
      subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta
      blocker with alpha-blocking activity, on exercise capacity and hormone levels
      during exercise after a 2-week treatment period. Maximal oxygen uptake (VO2 max)
      and blood lactic acid concentration (LA) were measured during progressive
      exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for
      the constant workload exercise test. Humoral factors were measured after 20
      minutes of constant workload exercise. The administration of arotinolol
      significantly decreased systolic blood pressure and heart rate at rest and during
      exercise, but diastolic blood pressure did not change. No significant difference
      was found between arotinolol and placebo with regard to VO2 max and maximal
      workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE)
      levels at rest and during exercise did not differ between the two treatments. In
      contrast, plasma epinephrine (EN) levels at rest and during exercise were
      significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest
      did not differ between the two treatments. However, exercise caused a significant
      increase in ANP after arotinolol treatment. These findings suggest that
      arotinolol decreases blood pressure and heart rate without affecting exercise
      capacity.

PMID- 1381613
TI  - Cholecystokinin-induced changes in polysome structure regulate protein synthesis
      in pancreas.
AB  - Translational regulation of digestive enzyme synthesis during short-term
      stimulation by cholecystokinin-octapeptide (CCK-OP), was examined in minced
      rabbit pancreas by measuring protein synthesis and monitoring alterations in the
      size of polysomes attached to the rough endoplasmic reticulum (RER). The effect
      of CCK-OP on protein synthesis was determined by measuring [3H]leucine
      incorporation into trichloroacetic-acid-precipitable proteins. Concentrations of
      CCK-OP that caused maximal enzyme secretion (10 and 30 nM) decreased protein
      synthesis by approx. 50% compared to control. Protein synthesis returned to the
      control level 60 min after terminating the action of CCK-OP. Autoradiography of
      [35S]methionine-labeled proteins separated by one-dimensional SDS-polyacrylamide
      gel electrophoresis demonstrated that CCK-OP reversibly inhibited the synthesis
      of all of the major groups of digestive enzymes. Northern blot analysis revealed
      that CCK-OP did not alter the cellular content of amylase and elastase mRNA.
      Incubation with CCK-OP caused a decrease in the size distribution of RER-bound
      polysomes. Polysome profiles returned to the control pattern 60 min following
      termination of the stimulus. These results suggest that the inhibitory effects of
      CCK-OP on the synthesis of digestive enzymes is regulated at translation by
      decreasing the number of RER-bound ribosomes that are actively translating
      digestive enzyme mRNA.

PMID- 1381614
TI  - Differential regulation of glucose transporter isoforms by thyroid hormone in rat
      heart.
AB  - Since thyroid hormone stimulates cardiac metabolism, for which glucose is an
      important fuel, we examined the effects of thyroid hormone on glucose transporter
      gene expression in rat heart. Treatment of hypothyroid animals with T3 for up to
      6 days caused a 2-fold increase in GLUT4 mRNA at 1 day, and a 4-fold increase at
      6 days (per unit DNA). GLUT4 protein, however, was not increased. In contrast,
      GLUT1 mRNA was transiently decreased by T3 treatment at 1 and 3 days, but
      returned to normal by 6 days. Concomitantly, GLUT1 protein decreased to 18% of
      the control value at 6 days. In chronically hypothyroid or hyperthyroid rats,
      GLUT4 mRNA varied directly with thyroid status, but GLUT4 protein was invariant,
      consistent with the acute effects of T3 treatment. Moreover, hypothyroidism
      increased GLUT1 mRNA and protein expression. We conclude that, in contrast to
      previous observations in skeletal muscle, GLUT4 protein content in rat heart is
      not altered by thyroid hormone. Cardiac GLUT1 expression is increased in
      hypothyroidism, and suppressed by thyroid hormone, at both the protein and mRNA
      levels. The observed discrepancy between GLUT4 mRNA and protein levels suggests
      that post-transcriptional regulatory events play a major role in GLUT4 expression
      in rat heart.

PMID- 1381615
TI  - [Endothelium-derived relaxation factor from vessels--a nitrosyl iron complex with
      thiol-containing ligands (hypothesis)].
AB  - A hypothesis is presented concerning the nature of endothelium--derived relaxing
      factor (EDRF) of blood vessels--a compound isolated from endothelial cells under
      the effect of acetylcholine, bradykinin and other agents. This factor causes
      relaxation of the smooth muscles of these vessels. EDRF is suggested to be a
      nitrosyl complex of iron with low-molecular thiol-containing ligands, most
      probably with cysteine. Nitric oxide produced from arginine by NO-synthetase is
      their active component. Incorporation of NO into iron complexes stabilizes it
      providing transfer inside the cells and between them. Subsequent liberation of NO
      from these complexes results from the oxidation of thiol ligands.

PMID- 1381616
TI  - [Photochemical transformation of Hoescht 33258 dye molecules complexed with cell
      nucleus DNA under the effect of UV-irradiation].
AB  - It is found that with time a decrease of fluorescence intensity of the basic band
      at 460 nm and appearance of a new band of fluorescence of DNA-specific dye
      Hoechst 33258 in complex with the cell nucleus DNA under the action of UV
      emission are observed. It is shown that phototransformation is related to the
      withdrawal of the nitrogen atom proton of piperazine ring in an excited state of
      the complex of the dye Hoechst 33258 with the cell nucleus DNA.

PMID- 1381617
TI  - Construction of protein analogues by site-specific condensation of unprotected
      fragments.
AB  - The extreme sensitivity to periodate of 1-amino, 2-hydroxy compounds permits the
      selective conversion of N-terminal serine and threonine to an aldehydic group. We
      have used this reaction to construct analogues of human granulocyte colony
      stimulating factor (G-CSF) by allowing such oxidized peptides to react with
      others that have had a hydrazide derivative attached to the C-terminus by
      reversed proteolysis. Two recombinant analogues of G-CSF were used as starting
      materials. Both had only a single lysine residue (at position 62 and 75,
      respectively) followed immediately by a serine. Digestion of each analogue by the
      lysine-specific protease from Achromobacter lyticus gave two fragments, one of
      which could be N-terminally oxidized and the other converted to the C-terminal
      hydrazide derivative by reversed proteolysis using the same enzyme. After
      preliminary studies with model peptides, we first reacted the corresponding
      peptide pairs together and then, in order to eliminate the 64-74 disulfide loop,
      fragment 1-62 from the first analogue with fragment 76-174 from the second.
      Reactions are efficient (up to 80% product based on the oxidized fragment) and
      take place under very mild conditions. The hydrazone bond can easily be
      stabilized by reduction with NaBH3CN. This method represents a new, reasonably
      general route for the construction of large protein chimeras of precisely
      controlled structure.

PMID- 1381618
TI  - Kinetics and stability of delta 5-3-ketosteroid isomerase from Pseudomonas
      testosteroni in the system of reverse micelles of aerosol OT in isooctane.
AB  - Partially purified delta 5-3-ketosteroid isomerase (KSI) from Pseudomonas
      testosteroni was studied kinetically after solubilization in reverse micelles of
      aerosol OT (AOT) in isooctane and water, as regards its application to
      biotechnology. With delta 5,10-estren-17 beta-ol-3-one as a substrate, KSI
      displays an enzyme activity in the micellar system but a low stability. In the
      presence of urea, the enzyme is, however, stable. Kinetic parameters of the
      stabilized enzyme are highly sensitive to both the hydration degree of the
      surfactant and its concentration. The hypothesis of the geometric correspondence
      of a non-spherical enzyme and spherical micellar matrix is considered.

PMID- 1381619
TI  - The 23S-5S spacer of two rRNA loci of Streptococcus salivarius subsp thermophilus
      includes a promoter.
AB  - The nucleotide sequence of the 3' part of a ribosomal and transfer RNA locus from
      Streptococcus salivarius subsp thermophilus NST1403 was determined. The sequenced
      DNA fragment includes the 3' end of a 23S rRNA gene, a 5S rRNA gene, a tRNA(asn)
      gene and a potential transcriptional terminator. The tRNA gene does not encode
      for the CCA 3'terminus of mature tRNA. We compared this sequence to a promoter
      carrying DNA fragment sequence (P20) of Streptococcus salivarius subsp
      thermophilus A054 [1]. We found that the P20 sequence included the 3' end of a
      23S rRNA gene, a 5S rRNA gene and the 5' part of a tRNA(val) gene. The two 23S-5S
      spacer sequences are identical and contain a promoter and a potential 23S rRNA
      processing site. Therefore, 5S rRNA and tRNA genes could be transcribed from a
      promoter located within the 23S-5S spacer of at least two of the six rRNA loci.

PMID- 1381620
TI  - Identification and epidemiological typing of clinical and environmental isolates
      of the genus Rhodococcus with use of a digoxigenin-labeled rDNA gene probe.
AB  - Rhodococcus species are ubiquitous in the environment, and several species have
      been reported to have pathogenic potential for humans. Rhodococcus equi, in
      particular, has been reported to cause infections in patients with AIDS. However,
      the identification of Rhodococcus species with use of conventional biochemical
      tests is problematic, and no simple and reproducible method exists for their
      rapid identification and differentiation. We found that the type strains of the
      20 recognized species in the genus Rhodococcus could be clearly distinguished
      with use of a combination of the Pvu II and Pst I rRNA gene restriction
      endonuclease patterns and a digoxigenin-labeled Escherichia coli rDNA probe.
      Analysis of four clinical or environmental isolates confirmed as Rhodococcus
      bronchialis showed no interstrain variation of rRNA gene bands. Analysis of 15
      isolates confirmed as R. equi from 13 patients showed 11 different rRNA gene
      patterns. No discernible difference was observed in the ribotype patterns between
      R. equi isolates from patients for whom AIDS had been diagnosed and those from
      patients who did not have AIDS, and there was no evidence of geographic
      clustering of R. equi ribotype patterns. Three of five Rhodococcus species
      isolates that could not be differentiated with use of conventional biochemical
      methods were identified with use of ribotype analysis. Therefore, ribotype
      analysis may provide an important adjunct to current biochemical identification
      of environmental and clinical isolates of Rhodococcus species.

PMID- 1381621
TI  - Hypothesis for vaccine development: protective immunity to enteric diseases
      caused by nontyphoidal salmonellae and shigellae may be conferred by serum IgG
      antibodies to the O-specific polysaccharide of their lipopolysaccharides.
AB  - Immunoprophylaxis for bacterial enteric diseases is hindered because the
      protective immune mechanism(s) against nontyphoidal salmonellae or shigellae in
      humans are not established. On the basis of the similarities between the clinical
      signs, epidemiology, pathogenesis, and pathology of as well as protective
      immunity to salmonellae and shigellae, we propose that serum IgG antibodies to
      the O-specific polysaccharide (O-SP) of their lipopolysaccharides (LPSs) will
      confer protective immunity to these two pathogens. Critical to this notion is
      that (1) the virulence of these two pathogens requires full expression of their
      LPS; (2) active or passive immunization with serum IgG O-SP antibodies confers
      protection of mice against Salmonella typhimurium (there are no comparable data
      for humans); and (3) in humans, convalescence from shigellosis confers type (O
      SP) -specific protective immunity, and indirect evidence shows a correlation
      between the level of serum LPS antibodies and resistance to shigellosis. We
      designed conjugate vaccines to elicit high levels of long-lived serum IgG O-SP
      antibodies to nontyphoidal salmonellae and shigellae to test this hypothesis.

PMID- 1381622
TI  - Transcripts of the mitochondrial gene ND5 are overexpressed in highly metastatic
      murine large cell lymphoma cells.
AB  - The relative levels of mitochondrial specific gene transcripts were compared in
      two murine large cell lymphoma cell lines that differ in their propensities to
      form liver metastases and in their sensitivity to macrophage mediated antitumor
      cytostasis and cytolysis. Full-length transcripts of the mitochondrial genes were
      hybridized on electroblots from citrate/urea gels with specific gene prodes. The
      mitochondrially encoded gene NADH dehydrogenase subunit 5 (ND5), that encodes a
      component of NADH dehydrogenase (complex I) of the electron transport chain, was
      significantly overexpressed in the highly metastatic RAW117-H10 compared to low
      metastatic RAW117-P cells. Results from analysis of RNA blots were confirmed in
      an S1 nuclease protection assay. Since RAW117-H10 cells are significantly more
      resistant to cytostasis by activated macrophages in coculture and such macrophage
      activity can inhibit RAW117 tumor cell respiration and growth, a mechanism was
      suggested that allows RAW117 cell escape from certain host effector mechanisms
      that block cellular respiration by an increase in the in vivo concentrations of
      translatable messenger RNA (mRNA) that codes for key components of the electron
      transport chain.

PMID- 1381623
TI  - Role of the modified (glycosaminoglycan producing) perisinusoidal fibroblasts in
      the CCl4-induced fibrosis of the rat liver.
AB  - Development and regression of liver fibrosis and cirrhosis induced by CCl4 in
      male F-344 rats were strictly followed during and after an 8-week treatment. The
      relative amount of collagen was measured by morphometry and the number of
      glycosaminoglycan (GAG) containing fat storing cells was counted at each time
      point. The expression of proteoglycan genes (decorin, versican and BPG-5 HSPG)
      was studied in parallel with the development of cirrhosis. Collagen content of
      the liver as well as the number of GAG-containing mesenchymal (fat storing) cells
      increased in parallel until two weeks after the cessation of CCl4 treatment.
      Later, both the collagen content and the number of GAG-containing cells decreased
      in parallel and significantly. Proteoglycan gene expression in the nonparenchymal
      fraction of liver cells indicated an active proteoglycan synthesis in the course
      of the development of cirrhosis. It is concluded that modified Ito (fat storing)
      cells synthesize proteoglycans and play an important role in the formation of
      connective tissue fibers in liver fibrosis.

PMID- 1381624
TI  - The development of granulocyte colony-stimulating factor in its various clinical
      applications.

PMID- 1381625
TI  - Ex vivo expansion and maturation of peripheral blood CD34+ cells into the myeloid
      lineage.
AB  - Hematopoietic reconstitution (HR) after peripheral blood stem cell
      transplantation is characterized by a delay of 8 and 12 days for recovery to safe
      levels of neutrophils and platelets even in patients with the most rapid
      engraftment. We postulate that a further enhancement in the rate of HR may be
      achieved by transplanting with an expanded postprogenitor cell population that
      can provide mature functional cells within days of infusion. In this study we
      investigated the ability of combinations of hematopoietic growth factors (HGF) to
      generate nascent granulocyte-macrophage colony-forming units (CFU-GM) in a 7-day
      suspension culture of peripheral blood CD34+ cells. A combination of 6 HGF, ie,
      interleukin-1 beta (IL-1), IL-3, IL-6, granulocyte colony-stimulating factor (G
      CSF), granulocyte-macrophage-CSF (GM-CSF), and stem cell factor (SCF), was
      identified as the most potent combination of those tested. Subsequently, large
      volume suspension cultures of CD34+ cells from the same patients using the same 6
      factor combination were established and monitored for 21 days. An exponential
      rate of nucleated cell production (mean 1,324-fold increase) occurred during
      culture. CFU-GM production paralleled nucleated cell production until day 10,
      peaked at day 14 (mean 66-fold increase), and was then maintained until day 21.
      Cells produced in culture were predominantly neutrophil precursors and developed
      normally as assessed by morphology, immunophenotype, and superoxide generation.
      This stroma-free, cytokine-driven culture system can achieve a degree of
      amplification, which suggests the feasibility of ex vivo culture of hematopoietic
      progenitor cells as an adjunct to hematopoietic stem cell transplantation.

PMID- 1381626
TI  - Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non
      Hodgkin's lymphoma: a randomized controlled trial.
AB  - The effect of granulocyte colony-stimulating factor (G-CSF) on neutropenia,
      infection, and cytotoxic chemotherapy administration was studied in a randomized
      trial in patients receiving intensive weekly chemotherapy for non-Hodgkin's
      lymphoma (NHL). Eighty patients (aged 16 to 71 years) with high-grade NHL (Kiel)
      of any stage were randomized to receive VAPEC-B chemotherapy alone (39 patients)
      or with G-CSF administered as a daily subcutaneous dose of 230 micrograms/m2 (41
      patients). Prophylactic ketoconazole and cotrimoxazole were administered to all
      patients throughout treatment. The protocol specified identical dose modification
      and antibiotic treatment criteria bor both groups. Neutropenia (absolute
      neutrophil count [ANC] less than 1.0 x 10(9)/L) occurred in 15 of 41 (37%) of the
      G-CSF-treated patients and in 33 of 39 (85%) of the controls, giving a relative
      risk for control patients of 2.31 (95% confidence interval [CI], [1.51, 3.54]; P
      = .00001). Fever (greater than or equal to 37.5 degrees C) with neutropenia (ANC
      less than 1.0 x 10(9)/L) occurred in 9 of 41 (22%) of the G-CSF group and in 17
      of 39 (44%) of the controls (relative risk for control, 2.26; 95% CI [1.01,
      5.06]; P = .04). There were fewer treatment delays, with shorter duration (P =
      .01) in patients receiving G-CSF. Chemotherapy doses were reduced in 4 of 41
      (10%) of the G-CSF patients and 13 of 39 (33%) of the controls (P = .01). The
      dose intensity of cytotoxic chemotherapy was significantly increased in patients
      receiving G-CSF (median of 95% in G-CSF group compared with 83% in control
      patients). Three vascular deaths occurred in the G-CSF group. Delays in the
      control group most commonly resulted from neutropenia (19 patients, compared with
      2 patients in the G-CSF-treated group, P = .000007). Severe mucositis was the
      major dose-limiting toxicity in G-CSF-treated patients, but did not occur more
      frequently than in controls (15 patients in each group). Overall, patients
      randomized to receive G-CSF achieved a greater dose intensity than control
      patients, but this did not result in significant differences in drug toxicity
      (other than neutropenia), intravenous antibiotic usage, or hospitalization
      between the two groups.

PMID- 1381627
TI  - c-kit Gene was not transcribed in cultured mast cells of mast cell-deficient
      Wsh/Wsh mice that have a normal number of erythrocytes and a normal c-kit coding
      region.
AB  - The Wsh is a mutant allele at the W (c-kit) locus of mice. Mice of Wsh/Wsh
      genotype have white hairs and black eyes. Although adult C57BL/6-Wsh/Wsh mice
      were not anemic, they showed a remarkable depletion of mast cells. Most
      homozygous or double heterozygous mutant mice at the W (c-kit) locus, of which
      mast-cell depletion was comparable to that of Wsh/Wsh mice, are deficient in germ
      cells. However, male and female Wsh/Wsh mice have an appreciable number of germ
      cells in their gonads. We investigated the mechanism of specific depletion of
      mast cells in Wsh/Wsh mice. Cultured mast cells (CMC) derived from the spleen of
      Wsh/Wsh mice neither attached to normal (+/+) fibroblasts nor survived in the
      coculture with +/+ fibroblasts. The c-kit messenger RNA (mRNA) was strongly
      expressed in +/+ CMC, but not detectable in Wsh/Wsh CMC. Despite the lack of c
      kit mRNA in Wsh/Wsh CMC, the c-kit mRNA was normally detectable in the cerebellum
      and weakly detectable in the testis and spleen of Wsh/Wsh mice. No significant
      changes were found in the nucleotide sequence of the c-kit transcripts obtained
      from the cerebellum of Wsh/Wsh mice. Development of mast cells, erythrocytes, and
      germ cells in Wsh/Wsh mice appeared to be parallel with the magnitude of the c
      kit gene expression in each cell type.

PMID- 1381628
TI  - Low c-kit expression of cultured mast cells of mi/mi genotype may be involved in
      their defective responses to fibroblasts that express the ligand for c-kit.
AB  - Mutant mice of mi/mi genotype are osteopetrotic and deficient in tissue mast
      cells due to a defect in osteoclasts and mast cells. In an effort to further
      understand the mechanisms behind why mi/mi mouse-derived cultured mast cells
      (mi/mi-CMC) responded to interleukin-3 (IL-3), but not to the proliferative
      stimuli presented by fibroblasts, mi/mi-CMC and congenic normal (+/+) mouse
      derived CMC (+/+-CMC), both of which expressed the phenotypic characteristics of
      immature mast cells, were cocultured with Swiss albino/3T3 fibroblasts in a
      medium containing IL-3. In the in vitro CMC/fibroblast coculture, mi/mi-CMC did
      not acquire the phenotypes of connective tissue-type mast cells (CTMC), while +/+
      CMC did. In addition, attachment of mi/mi-CMC to the fibroblasts was found to be
      significantly lower than that of +/+-CMC. Because the interaction of c-kit
      product with its ligand (stem cell factor [SCF]) is known to play an important
      role not only in proliferation and differentiation of mast cells but also in
      attachment of CMC to fibroblasts, the expression and function of c-kit were
      investigated in mi/mi-CMC and +/+-CMC. Recombinant rat SCF (rrSCF164) induced a
      dose-dependent proliferation of +/+-CMC. Also, rrSCF164 induced +/+-CMC to
      acquire the phenotypes of CTMC in the medium containing IL-3. By contrast,
      rrSCF164 did not stimulate the proliferation of mi/mi-CMC nor induce a phenotypic
      change of the cells from immature mast cells to mature, CTMC-like mast cells.
      Immunoblotting with antiphosphotyrosine antibody showed that rrSCF164 induced
      considerable tyrosine phosphorylation of 145- to 165-Kd protein, the product of c
      kit, in +/+-CMC, whereas tyrosine phosphorylation of the protein was barely
      detectable in mi/mi-CMC. Northern blot and flow cytometry analyses showed that
      mi/mi-CMC expressed much less c-kit at both protein and message levels than +/+
      CMC. Further, mi/mi-CMC were found to differ from +/+-CMC in the expression of
      mouse mast cell protease-6 (MMCP-6) and MMCP-2 messenger RNA transcripts. These
      results suggest that the gene product of the mi locus may be important in
      regulating the expression of gene products such as c-kit, and that mast cell
      deficiency of mi/mi mice appears to be due, at least in part, to impaired
      signaling through the c-kit receptor because of the low c-kit expression.

PMID- 1381629
TI  - Immunosuppressants FK506 and rapamycin function as reversal agents of the
      multidrug resistance phenotype.
AB  - The multidrug-resistant (MDR) phenotype is characterized in vitro by the
      resistance displayed by cell lines to a broad spectrum of natural product
      cytotoxic agents. This high level of cross-resistance is due to the increased
      expression of a membrane glycoprotein termed P-glycoprotein. Encoded in humans by
      the mdr1 gene, P-glycoprotein functions as an energy-dependent efflux pump of
      these cytotoxic agents. In this report, we demonstrate that the newly
      characterized immunosuppressant FK506 and its structural analogue, rapamycin, are
      capable of functioning as MDR reversal agents. FK506 and rapamycin increase both
      intracellular, cytotoxic drug (daunomycin) accumulation, and the cytotoxicity of
      chemotherapeutic agents in multidrug-resistant cells. The increase in cytotoxic
      drug accumulation is observed at concentrations of FK506 and rapamycin 1,000-fold
      greater than the concentrations required for FK506 and rapamycin to inhibit T
      lymphocyte activation and similar to those shown to be effective for other MDR
      reversal agents such as cyclosporine A (CsA) and verapamil. The effect of FK506
      or rapamycin on both intracellular accumulation and cytotoxicity of daunomycin is
      additive. This is supported by the ability of FK506 and rapamycin to directly
      compete the binding of the photoaffinity analogue 125I-iodoaryl azidoprazosin to
      the P-glycoprotein. The data demonstrate that FK506 and rapamycin represent a new
      class of structurally distinct molecules that can function as MDR reversal agents
      and suggest a previously unidentified, potential clinical role for these
      compounds.

PMID- 1381630
TI  - Induction of erythroid differentiation and fetal hemoglobin production in human
      leukemic cells treated with phenylacetate.
AB  - There is considerable interest in identifying nontoxic differentiation inducers
      for the treatment of various malignant and nonmalignant blood disorders,
      including inborn beta-chain hemoglobinopathies. Using the human leukemic K562
      cell line as a model, we explored the efficacy of phenylacetate, an amino acid
      derivative with a low toxicity index when administered to humans. Treatment of
      K562 cultures with pharmacologically attainable concentrations of phenylacetate
      resulted in erythroid differentiation, evident by the reduced growth rate and
      increased hemoglobin production. The effect was time- and dose-dependent, further
      augmented by glutamine starvation (phenylacetate is known to deplete circulating
      glutamine in vivo), and reversible upon cessation of treatment. Molecular
      analysis showed that phenylacetate induced gamma globin gene expression with
      subsequent accumulation of the fetal form of hemoglobin (HbF). Interestingly, the
      addition of phenylacetate to antitumor agents of clinical interest, eg,
      hydroxyurea and 5-azacytidine, caused superinduction of HbF biosynthesis. The
      results suggest that phenylacetate, used alone or in combination with other
      drugs, might offer a safe and effective new approach to treatment of some
      hematopoietic neoplasms and severe hemoglobinopathies.

PMID- 1381631
TI  - Quantitation of CD34+ cells.

PMID- 1381632
TI  - Microbiologic and pathologic aspects of pulpal and periapical disease.
AB  - The greatest cause of endodontic and periapical pathosis is microbial infection
      of the pulp. Most odontogenic infections are of a polymicrobial nature. With
      advances in anaerobic isolation and culturing techniques, much has been learned
      about the presence of pathogenic organisms such as Porphyromonas and Prevotella
      species (formerly classified as black-pigmented Bacteroides species) in infected
      root canals. This review provides a summary of recent developments in endodontic
      microbiology, virulence factors, and host defense systems as they relate to the
      pathogenesis of pulpal and periapical inflammatory lesions.

PMID- 1381634
TI  - Gram-positive infection in surgery--the role of teicoplanin. Proceedings of a
      symposium within the 17th International Congress of Chemotherapy. Berlin, 25 June
      1991.

PMID- 1381633
TI  - Gram-positive infection in surgery--the role of teicoplanin. Introduction.

PMID- 1381635
TI  - Teicoplanin in open fractures: a preliminary report.
AB  - The occurrence of infection following open fractures varies with the severity of
      the fracture and associated soft tissue damage. In order to study the effect of
      antibiotics given prophylactically, teicoplanin has been used in a prospective
      study. On admission, fractures were graded according to the severity of the
      tissue damage: Type I--soft tissue injury less than 1 cm Type II--soft tissue
      injury more than 1 cm. Type III fractures characterized by extensive soft tissue
      and bone damage were not included in the study. Type I patients were given a
      single dose of teicoplanin, 400 mg i.v.; Type II patients were given a single
      dose of teicoplanin, 400 mg i.v., followed by two further intravenous injections
      at 12 and 24 hours. Patients were assessed for the presence of wound and bone
      infections and follow up was for 1 year. Preliminary results, predominantly from
      Type II fractures involving long bones, show that teicoplanin is effective in
      lowering the incidence of infection following open fractures.

PMID- 1381636
TI  - Teicoplanin vs cephamandole for antimicrobial prophylaxis in prosthetic joint
      implant surgery: (preliminary results).
AB  - Infection following prosthetic joint implant jeopardizes the prosthesis and may
      lead to long-term locomotor disability. Interoperative antimicrobial prophylaxis
      can reduce the incidence of infectious complications. The comparative safety and
      efficacy of single-dose teicoplanin and four doses of cephamandole over a 24-hour
      period is currently being assessed in a single-blind, randomized concurrent study
      of patients who undergo first time hip or knee arthroplasty. Of 660 evaluated
      patients, 352 have received cephamandole and 308 teicoplanin. Two patients in
      each group had a surgical wound infection at 1 week after surgery. Reassessment
      30 days postoperatively showed resolution of the infection in both of the
      teicoplanin patients and in one of the cephamandole patients. Proven or suspected
      infection involving other body systems occurred in 30 teicoplanin and 38
      cephamandole patients at 1 week postoperatively and in 5 teicoplanin and 3
      cephamandole patients 1 month after surgery. Adverse events occurred in 20 (5.1%)
      teicoplanin patients and 29 (7.1%) cephamandole patients. These preliminary
      results suggest that single-dose teicoplanin is a safe and effective prophylactic
      agent in prosthetic joint implant surgery.

PMID- 1381637
TI  - Teicoplanin--home therapy for prosthetic joint infections.
AB  - Infection with methicillin-resistant organisms is increasingly common among
      implanted orthopaedic devices. The organisms involved are often multiresistant to
      other commonly used antibiotics. Rifampicin resistance is less common at
      isolation but may develop during treatment unless combination therapy with
      another drug is employed. However, tolerance of combinations is poor,
      particularly among elderly patients. These patients may require at least 6 weeks
      of antibiotic therapy, and where there is no suitable oral therapy, this has
      meant prolonged hospitalization solely for administration of parenteral
      antibiotics. Recently we have started treating such patients with teicoplanin, 6
      mg/kg once daily, by intravenous bolus injection. The injections are administered
      by relatives at home and the patients attend the ward twice weekly for inspection
      and changing of the intravenous cannula. The potential for home administration of
      parenteral teicoplanin gives this drug a major advantage over other parenteral
      drugs for the treatment of prosthetic joint infections.

PMID- 1381638
TI  - Teicoplanin--domiciliary use in surgical infections.
AB  - This is an ongoing study designed to evaluate the role of teicoplanin in the
      therapy of sternal wound infections following cardiac surgery caused by Gram
      positive microorganisms. Intravenous teicoplanin therapy is begun in the
      hospital, but once the patients return home it is given as a single intramuscular
      dose of 400 mg/day. Only a limited number of patients have been recruited so far,
      but in these, the clinical success rate and the bacteriological elimination rate
      are 85%. Only one patient had to be withdrawn from the study due to intolerable
      side-effects. These preliminary results suggest that teicoplanin is suitable for
      the therapy of chest wound infections following cardiac surgery; a major part of
      the course can be administered at home in a single daily intramuscular injection.
      This novel therapy regimen is expected to reduce considerably the hospital costs
      involved in the therapy of sternal wound infections.

PMID- 1381639
TI  - Teicoplanin--its role as systemic therapy of burn infections and as prophylaxis
      for orthopaedic surgery. Italian Study Groups for Antimicrobial Prophylaxis in
      Orthopaedic Surgery and Burns.
AB  - Two randomized studies have been initiated to establish the role of teicoplanin
      as systemic therapy for infections in burns patients and as short-term
      prophylaxis for orthopaedic implant surgery. Opportunistic micro-organisms
      causing infections in burn patients are often acquired in hospital. These
      infections commonly involve Gram-positive organisms which may be resistant to
      several antibiotics. Teicoplanin, alone and in combination with additional
      antibacterial drugs, is effective in the treatment of Gram-positive infections of
      various types. In addition, teicoplanin has proved useful as prophylaxis against
      infection in orthopaedic surgery. Deep prosthetic infections are very difficult
      to cure without removing the infected device; the outcome can be devastating,
      such as total loss of joint function, amputation, and, occasionally, death.
      Preliminary results from the two studies are encouraging and show that
      teicoplanin has a role to play both in treatment of infection and as prophylaxis
      against hospital-acquired infection.

PMID- 1381640
TI  - Antibiotic prophylaxis in clean surgical cases and the role of community
      surveillance.
AB  - In an ongoing prospective study of clean surgical procedures, patients have been
      examined by specialist research nurses on a minimum of three occasions during the
      postoperative period to determine the incidence of wound complications. Whereas a
      previous retrospective audit suggested a wound infection rate of 2%, this
      community surveillance programme revealed the true rate as at least fourfold
      greater (p less than 0.001). Of these complications, more than 70% were detected
      only by the surveillance programme. Immediate benefit was obtained by a reduction
      in all complications. Despite these improvements, a core of postoperative sepsis
      remained, particularly in high-risk cases. Thus, a prospective, controlled,
      prophylactic antibiotic trial has been undertaken, in an attempt to reduce the
      infection rate still further. An antibiotic regimen of teicoplanin, 400 mg i.v.,
      given as a single dose, was chosen because of the excellent activity of this
      agent against staphylococci and streptococci, and also because of the long half
      life which renders it suitable for single-dose administration.

PMID- 1381641
TI  - Efficacy, tolerability and pharmacokinetics of teicoplanin in patients undergoing
      breast surgery.
AB  - In a prospective open trial, 21 female patients undergoing breast surgery
      received a single intravenous bolus injection of teicoplanin, 400 mg, 30 minutes
      before the operation. During surgery, (1 hour after teicoplanin administration),
      samples of breast and fat tissue and serum were collected; 24 hours and 48 hours
      after dosing, samples of wound exudate were taken. Teicoplanin concentrations
      were determined using the RASA method. Teicoplanin levels were lowest in fat
      tissue. Teicoplanin levels in wound exudate were found to be satisfactorily high.
      However, teicoplanin levels in fat and breast tissue and in wound exudate
      exceeded the MIC90 for various staphylococcus strains, such as S. aureus and S.
      epidermidis. No local or systemic adverse reactions were observed during the
      trial. Teicoplanin was well tolerated. Preliminary results from this trial,
      therefore, indicate that teicoplanin may be a suitable antibiotic for use in the
      prophylaxis of infection in breast surgery.

PMID- 1381642
TI  - Teicoplanin and prophylaxis of Hickman catheter insertions.
AB  - A total of 88 patients with haematological malignancies who required Hickman
      catheters for intensive chemotherapy, were randomized to receive either a single
      bolus intravenous injection of teicoplanin, or no teicoplanin, immediately before
      insertion of a double lumen Hickman catheter. There was a lower incidence of
      catheter-related Gram-positive sepsis in patients receiving prophylactic
      teicoplanin. This benefit was particularly clear in patients who were already
      neutropenic at the time of catheter insertion. Prophylactic teicoplanin may,
      therefore, be useful as a routine procedure during the insertion of Hickman
      catheters for this group of patients.

PMID- 1381643
TI  - Teicoplanin vs cephradine and metronidazole in the prophylaxis of sepsis
      following vascular surgery: an interim analysis of an ongoing trial.
AB  - This paper presents further preliminary results of a trial of the prophylaxis of
      sepsis in 165 patients undergoing vascular surgery. The efficacy and safety of a
      single dose of teicoplanin was examined and compared with three doses of
      cephradine plus metronidazole. No significant differences were detected in the
      prophylactic efficacy in either group. The first interim report indicated
      abnormalities in liver function, maximum at 7 days, in both groups. These
      findings are confirmed in this second interim report. Raised levels of GGT and
      alkaline phosphatase are more prominent in patients receiving teicoplanin. Liver
      function improved by 28 days, however, suggesting that any abnormality is
      transient.

PMID- 1381644
TI  - Teicoplanin in the treatment of bone and joint infections. Teicoplanin Bone and
      Joint Cooperative Study Group, USA.
AB  - Teicoplanin is a new glycopeptide antibiotic with activity against Gram-positive
      bacteria, including methicillin-resistant organisms. Teicoplanin is administered
      once daily, either intravenously or intramuscularly. Teicoplanin was given once
      daily, intravenously or intramuscularly, in the treatment of hospitalized or
      ambulatory patients with Gram-positive bone or joint infections. A total of 90/98
      patients were evaluated for efficacy; 41 had acute osteomyelitis, 41 had chronic
      osteomyelitis, and 8 had septic arthritis. At the end of therapy, 37 acute
      osteomyelitis patients were cured/improved with a 90% cure rate at 6-month follow
      up; 2 relapsed and 1 failed. At the end of therapy 30 chronic osteomyelitis
      patients were cured/improved with an 88% cure rate at 6-month follow-up; 2
      relapsed and 1 failed. 100% of the septic arthritis patients were cured at the
      end of therapy and at 1-month follow-up. The most common bacterial isolates
      cultured from bone were S. aureus (39 isolates), S. epidermidis (11 isolates),
      other coagulase-negative staphylococci (20 isolates), enterococci (6 isolates),
      and other streptococcal species (20 isolates). The most common bacterial isolates
      cultured from joint fluid were S. aureus (6 isolates) and S. epidermidis (2
      isolates). All patients tolerated the intramuscular or intravenous routes of
      administration well. Adverse reactions were mild and most cases did not require
      discontinuation of therapy. The majority of therapy was administered on an
      outpatient basis. Teicoplanin was safe, effective, convenient and relatively well
      tolerated in patients with acute or chronic osteomyelitis or septic arthritis.

PMID- 1381645
TI  - Vitronectin-binding surface proteins of Staphylococcus aureus.
AB  - S. aureus strain ISP 546 was selected (of 55 strains tested) to define optimal
      conditions for expression of vitronectin binding. High binding was expressed when
      the strain was grown on blood agar and in Todd-Hewitt broth. Binding was optimal
      in the 6.0 to 7.2 pH range and was unaffected by divalent cations and ionic
      strength. Binding was partially inhibited by D-mannose, heparin, types I and IV
      collagen, fibronectin, fibrinogen and vitronectin, but was not affected by other
      carbohydrates or glycoproteins tested. Cell surface binding components were
      extracted with the aid of 1 M LiCl (pH 5.0) from strain ISP 546 grown in Todd
      Hewitt broth. Vitronectin binding proteins were purified by affinity
      chromatography on heparin-Sepharose. Fractions inhibiting binding of 125I
      labelled vitronectin to strain ISP 546 were eluted by 0.01 M NaOH, dialysed,
      concentrated and subjected to SDS-PAGE. Silver staining revealed one major band
      (70 kDa) and two minor bands (34 and 36 kDa).

PMID- 1381646
TI  - Binding of laminin, type IV collagen, and vitronectin by Streptococcus
      pneumoniae.
AB  - Forty-three strains of Streptococcus pneumoniae were tested for their ability to
      bind radiolabelled laminin, collagen types I, II and IV, fibronectin, and
      vitronectin. Two basement membrane components, laminin and type IV collagen,
      interacted with many S. pneumoniae strains. All strains bound laminin and 28
      (65%) bound collagen type IV. Approximately 60% of the strains bound vitronectin
      but only a few strains showed low binding of fibronectin and collagen type I and
      II.

PMID- 1381647
TI  - Some biochemical characteristics of a partially purified extracellular keratinase
      from Trichophyton schoenleinii.
AB  - A Trichophyton schoenleinii (T. schoenleinii) strain from tinea favus was
      cultured in a liquid medium, from which an extracellular keratinase extract was
      obtained. The keratinase was partially purified with carboxymethyl-cellulose
      (CMC) column chromatography. Some biochemical characteristics of the keratinase
      were then examined. Its molecular weight was estimated to be 38,000 on sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The optimal
      temperature was 50 degrees C, and the optimal pH value was 5.5. The keratinolytic
      activity was specifically increased by Fe++ and Fe .

PMID- 1381649
TI  - Axonal blockade induces the expression of vasoactive intestinal polypeptide and
      galanin in rat dorsal root ganglion neurons.
AB  - Nerve growth factor (NGF) undergoes retrograde transport from peripheral target
      organs, and has been recently reported to regulate the production of some
      neuropeptides in dorsal root ganglion (DRG) neurons. Therefore, to ascertain
      whether or not the expression of calcitonin gene-related peptide (CGRP),
      vasoactive intestinal polypeptide (VIP), and galanin was regulated by the
      retrograde transport of factors such as NGF, we carried out an immunocytochemical
      analysis using vinblastine as an axonal transport blocker and a monoclonal
      antibody to the NGF receptor (NGFR) as a marker of NGF-responsive neurons. The
      percentage of CGRP-containing DRG neurons (L5) was decreased by sciatic nerve
      transection or by the application of higher doses of vinblastine (0.3-0.6 mM) to
      the sciatic nerve. VIP and galanin were expressed in some DRG neurons after the
      application of a low dose of vinblastine (0.15 mM), which can block axonal flow
      without causing neuronal damage. The expression of these peptides was not
      affected by dorsal rhizotomy. About 70% of the CGRP-containing neurons also
      expressed NGFR, while most of the VIP-containing or galanin-containing neurons
      lacked NGFR. These findings indicate that the depletion of peripheral target
      derived neurotrophic factor(s) other than NGF by axonal blockade may induce the
      gene expression of VIP and galanin.

PMID- 1381648
TI  - Nicotinic and muscarinic modulation of 5-hydroxytryptamine (5-HT) release from
      porcine and canine small intestine.
AB  - Strips of porcine and canine small intestine were incubated in vitro and the
      release of 5-hydroxytryptamine (5-HT) was determined by HPLC with electrochemical
      detection. The spontaneous outflow of 5-HT from the porcine and canine small
      intestine largely reflects calcium-dependent 5-HT secretion from enterochromaffin
      cells which are under a spontaneous neuronal, excitatory input as indicated by
      the inhibitory effect (30-40%) of tetrodotoxin. In both species, nicotine
      enhanced the release of 5-HT in a concentration-dependent manner by a maximum of
      about 50% at 100 microM. This effect was blocked by the nicotine receptor
      antagonist hexamethonium, but not by the subtype-selective nicotine receptor
      antagonist alpha-bungarotoxin. The effect of nicotine was rapidly desensitized.
      The presence of tetrodotoxin abolished the effect of nicotine on 5-HT release in
      canine tissue but not in porcine tissue. The presence of the muscarine receptor
      antagonist scopolamine prevented the effect of nicotine on 5-HT release from
      canine tissue, but significantly enhanced 5-HT release from porcine tissue. The
      muscarine receptor agonist oxotremorine inhibited 5-HT release from porcine
      tissue, but increased 5-HT release from canine tissue. However, in the presence
      of tetrodotoxin, oxotremorine enhanced 5-HT release in tissue from both species.
      In conclusion, activation of nicotine receptors induce the release of 5-HT from
      porcine and canine small intestine. In the dog, the effect of nicotine is
      mediated via the release of acetylcholine which then stimulates 5-HT release via
      muscarine receptors on the enterochromaffin cells. In the pig, the stimulatory
      effect of nicotine appears to be located directly on the enterochromaffin cells.
      In addition, activation of neuronal muscarine receptors in the porcine small
      intestine induced the release of a previously unidentified neurotransmitter which
      inhibited 5-HT release. Nicotine, via cholinergic interneurons, also appears to
      induce the release of this inhibitory neurotransmitter which opposes the direct
      stimulatory action of nicotine on 5-HT release.

PMID- 1381650
TI  - Origins and collateralization of corticospinal, corticopontine, corticorubral and
      corticostriatal tracts: a multiple retrograde fluorescent tracing study.
AB  - Cerebral cells of origin for the corticospinal (CST), corticopontine (CP),
      corticorubral (CR) and corticostriatal (CS) fibers in the rat were identified
      following the simultaneous retrograde transport of propidium iodide (PI), fast
      blue (FB), fluorogold (FG) and diamidino yellow (DY). PI was injected into the
      contralateral C4 spinal cord segment while FB, FG and DY were injected into the
      ipsilateral medial pontine nuclei, red nucleus and striatum, respectively.
      Labeled pyramidal neurons projecting corticospinal axons were contralateral to
      injection in lamina V and ranged in size from small to large. These CST neurons
      occupied two distinct cortical areas. The cortical neurons of origin for the
      corticopontine, corticorubral and corticostriatal fibers were ipsilateral to
      injections. Labeled neurons were localized in cortical lamina V for the
      corticopontine and corticorubral fibers while corticostriate neurons were located
      in laminae III, V and VI. The CP, CR and CS labeled cells occupied one large
      cortical area which topographically included parts of the medial (AGm) and
      lateral (AGl) agranular cortices and the primary (SI) somatosensory cortex.
      Considerable overlapping of the cortical neurons of origin for the four motor
      fiber systems was apparent. More than 98% of the labeled cells were single
      labeled while less than 2% were double labeled. No triple or quadruple labeled
      neurons were observed. Hence, morphological evidence is presented that cortical
      motor neurons project mainly individual, rather than collateral, axons to each of
      the four motor associated nuclei investigated in this study. However, only a few
      cortical neurons projected axons simultaneously to a maximum of two nuclei
      involved in the motor pathways.

PMID- 1381651
TI  - Changes in rapidly transported proteins associated with development of abnormal
      projections in the diencephalon.
AB  - The development of the hamster visual system is accompanied by striking changes
      in the pattern of proteins that are synthesized in retinal ganglion cells and
      rapidly transported to their nerve terminals. To determine whether any of these
      protein changes are regulated by interactions between the developing nerve
      endings and the cells with which they form synapses, we induced retinofugal axons
      to form abnormal projections in the lateral posterior (LP) nucleus of the
      thalamus and dense patches of hyperinnervation in the lateral geniculate nucleus
      (LGN) by removing their principal target, the superior colliculus (SC), the day
      after birth. Under these experimental conditions, two rapidly transported
      proteins, including the neural cell adhesion molecule, NCAM, showed significant
      changes in their time course of expression. NCAM, identified here using a
      monospecific antibody, is normally synthesized and transported at high levels at
      early stages of development and then declines during the second and third
      postnatal weeks. However, this decline was delayed when optic fibers were re
      routed. A second rapidly transported protein, M(r) = 67 kDa, pI = 4.7, normally
      shows a rise in its synthesis and transport during terminal arbor formation and a
      subsequent decline, but it also remained elevated for a prolonged period when the
      SC was absent. These findings cannot be accounted for by a simple delay in the
      retinal ganglion cells' program of axonal growth, since other rapidly transported
      proteins, including the growth-associated protein GAP-43, showed a normal
      developmental time-course when the SC was removed. Target interactions therefore
      appear to influence the retinal ganglion cells' expression of different proteins
      in a specific fashion.

PMID- 1381652
TI  - Anatomical and physiological study of interneurons in an oligosynaptic cutaneous
      reflex pathway in the cat hindlimb.
AB  - Morphological and physiological studies were undertaken in the cat lumbosacral
      spinal cord in order to examine individual last-order excitatory interneurons in
      the disynaptic pathway between low threshold superficial peroneal (SP) afferents
      and flexor digitorum longus (FDL) motoneurons. Last-order interneurons projecting
      to the FDL motor nucleus were visualized with activity-dependent trans-synaptic
      transport of lectin-conjugated horseradish peroxidase (WGA-HRP). The location of
      lumbar interneurons that responded at short latencies (less than 3 ms) to
      electrical stimulation of the SP nerve was further defined using extracellular
      recording. The projection of individual interneurons to motoneurons in the L6
      segment was defined by spike-triggered averaging of population ventral root
      potentials (VRPs) using the sucrose gap technique. Measurements of the central
      latencies from the arrival of the SP afferent volley to interneuron firing, and
      from interneuron spike to the onset of the VRP EPSPs, confirm the existence of a
      low threshold, disynaptic SP pathway that excited motoneurons. These data provide
      useful latency constraints for the interpretation of the synaptic length of
      cutaneous reflex pathways in the cat hindlimb.

PMID- 1381653
TI  - Neurokinin A-like immunoreactivity in articular afferents of the cat.
AB  - Dorsal root ganglion cells with axons innervating the cat's knee joint via the
      medial articular nerve were retrogradely labelled with Fast blue. Neurokinin A
      like immunoreactivity was found in 4.5 +/- 1.1% (mean +/- S.D. of 5 nerves and
      695 cells) of the articular afferents. Colchicine treatment of the ganglia
      increased the percentage of immunopositive cells to 8.5 +/- 0.7% (mean +/- S.D.
      of 6 nerves and 554 cells) after 3-22 h. The diameter distribution of the
      immunopositive somata ranged from 20 to 50 microns with a maximum at 26-30
      microns. Comparing the proportions of neurokinin A-immunopositive cells with
      those of substance P, it can be calculated on the basis of mRNA encoding that
      neurokinin A is synthetized in about half of the substance P-containing primary
      articular afferents.

PMID- 1381654
TI  - Effects of intracerebroventricularly administered neostigmine on hypothalamic
      monoaminergic neuronal activities in awake rats.
AB  - Hypothalamic neuronal activities of noradrenaline, dopamine and serotonin as well
      as serum glucose concentrations were simultaneously monitored 60 min after the
      third cerebroventricular injection of neostigmine, a cholinesterase inhibitor, in
      rats. Each neuronal activity was assessed from a ratio of the concentration of
      the major metabolite to that of its precursor monoamine itself by using the
      technique of gas chromatography-mass spectrometry. Neostigmine caused significant
      increases in serum glucose concentrations, hypothalamic noradrenergic and
      dopaminergic neuronal activities, and significantly suppressed hypothalamic
      serotonergic neuronal activity. All these responses to neostigmine were
      completely inhibited by the co-administration of atropine. These observations
      emphasize the important role of the interactions between cholinergic (muscarinic)
      and monoaminergic neurons in the brain.

PMID- 1381656
TI  - Substance P inhibits carbamylcholine-stimulated 22Na+ efflux from acetylcholine
      receptor-enriched Torpedo electroplaque membrane vesicles.
AB  - The effect of substance P on nicotinic acetylcholine receptor function was
      examined in Torpedo electroplaque membranes. The peptide inhibited
      carbamylcholine-stimulated 22Na+ efflux in a concentration-dependent manner. By
      irreversibly blocking spare receptors with alpha-bungarotoxin, the IC50 for
      substance P was shown to be less than 3 microM. Inhibition by substance P was
      slow relative to receptor activation by carbamylcholine, consistent with an
      enhancement of desensitization or a slow allosteric block.

PMID- 1381655
TI  - Cyclic AMP and the nicotinic response of bovine adrenal chromaffin cells.
AB  - The effects of cAMP analogs on the nicotinic responses of bovine adrenal
      chromaffin cells were examined by monitoring nicotine-induced whole cell
      currents, [3H]norepinephrine release, and membrane conductance changes. None of
      the three methods revealed an increased nicotinic response after treatment with
      cAMP analogs. The compounds did increase [3H]norepinephrine release from the
      cells but the effect was not exerted at the level of nicotinic receptors. Bovine
      adrenal chromaffin cells differ in this respect from chick ciliary ganglion
      neurons which do show increased nicotinic responses after treatment with cAMP
      analogs.

PMID- 1381658
TI  - [Neurotransmission and sudden infant death. Study of cerebrospinal fluid].
AB  - The study of 33 cerebrospinal fluids of infants victims of sudden death shows a
      very significant increase of the metabolites of dopamine and serotonin. These
      determinations, compared to a control group, indicate a failure, concerning these
      two neurotransmitters, which could induce a cardiorespiratory seizure. This
      failure has likely a multifactorial origin.

PMID- 1381657
TI  - [Isolation and characterization of monoclonal antibody directed against antigenic
      peptide presented by class I histocompatibility molecule].
AB  - We describe the isolation and several characteristics of a monoclonal antibody
      (X5.3.7) which recognizes a peptide derived from influenza virus nucleoprotein
      and presented by the murine class I major histocompatibility molecule Kd. X5.3.7
      is thus an example of an antibody capable of recognizing an epitope normally
      recognized by T cells.

PMID- 1381659
TI  - [Potentiation of the antitumoral effect of electrochemotherapy by immunotherapy
      with allogeneic cells producing interleukin 2].
AB  - Electrochemotherapy (ECT) is a new antitumour treatment which consists of
      delivering electric pulses to the tumour a few minutes after an intravenous
      injection of bleomycin. The antitumour efficacy of ECT is increased by local
      injections of interleukin 2 (IL2) in the oedema which appears at the site of the
      treated tumours. We have shown that tumour cells inoculated in syngeneic mice are
      rejected if IL2 secreting allo- or xenogeneic cells are co-injected with tumour
      cells. We report here the large increase of ECT therapeutical efficacy when
      allogeneic cells secreting IL2 are injected into the peri-tumoural oedema.

PMID- 1381660
TI  - Channels activated by stretch in neurons of a helix snail.
AB  - Single-channel recordings from central neurons of the helix snail, Cepaea
      nemoralis, revealed two types of channels that could be activated by stretch
      (i.e., by the membrane deformation produced when suction is applied to the patch
      pipette). One, a K+ channel (58 pS in physiological solution), was evident in
      excised and cell-attached patches. Its conductance in symmetrical [K+] solutions
      indicated a channel of high K+ permeability (PK = 3.4 x 10(-13) cm/s). Though
      osmoregulation has been suggested as a function for such channels, comparisons
      among molluscs indicate osmotic milieu does not govern their expression; Cepaea
      is terrestrial, and stretch-activated K+ channels similar to those described here
      occur in aquatic and marine molluscs. The second type of channel, observed only
      in excised patches, was Cl- permeant; it had a large conductance (130 pS) and was
      inactive prior to patch excision. Membrane tension may not be the physiological
      activator of either the K+ or Cl- channel; the channels are designated as stretch
      activated channels on the basis of their experimental behaviour during single
      channel recording.

PMID- 1381661
TI  - Partial inhibition of skeletal muscle contraction by dantrolene sodium and its
      modification with perchlorate and Bay K 8644.
AB  - The effects of dantrolene sodium (DAN) on the dihydropyridine receptor (DHPR) of
      the transverse (T) tubule voltage sensor (Ca2+ channel) was studied with single
      fibers from bullfrog toe muscle. Perchlorate (ClO4-), which acts selectively on
      the DHPR, overcame DAN-induced inhibition of twitch tension. Bay K 8644, a DHPR
      agonist, slowed the rate of twitch inhibition by DAN. DAN inhibited twitch
      tension to a greater extent in Ca(2+)-free solution than in Ringer solution or
      solution containing Zn2+, whereas twitch inhibition by DAN was less in caffeine
      containing solution than in the control. The effects of DAN on Zn(2+)- and
      caffeine-treated fibers and on fibers in Ca(2+)-free solution suggest that DAN
      must act near the voltage sensor of the T tubule. However, differences in net
      twitch inhibition by DAN between control fibers and fibers potentiated by ClO4-
      or Bay K 8644 suggest that DAN does not bind to the same site as these
      potentiating agents do. The role of myoplasmic Ca2+ in DAN-induced inhibition of
      twitch and the effects of DAN on the mechanical threshold and membrane potential
      in skeletal muscle are discussed.

PMID- 1381662
TI  - Nonselective cation channels in intact human T lymphocytes.
AB  - Nonselective cation channels were found in single channel recordings from cell
      attached patches on human T lymphocytes. These channels were active under
      conditions that should lead to cell swelling (hypotonic bath solutions with NaCl
      or KCl); however, a definite dependence of activity on cell swelling has not been
      proven. Under these conditions similar channels were found in 20 of 23 patches
      from 11 different blood donors. The current-voltage relation was approximately
      linear for outward current (11-14 pS) and inwardly rectifying (to 23 pS) when the
      intact cells were depolarized with high KCl in the bath. The voltage dependence
      of channel activity is consistent with closing at hyperpolarized membrane
      potentials (Vm less than or equal to -50 mV) and block of open channels at
      strongly depolarized membrane potentials (Vm greater than 0 mV). Reversal
      potentials under all ionic gradients tested are consistent with a channel that is
      poorly selective between Na+ and K+ ions. Active channels in cell-attached
      patches were rapidly blocked by bath addition of the membrane-permeant inhibitor
      quinine. Channels that were active in cell-attached became quiescent after patch
      excision; however, two patches remained active long enough to obtain current
      voltage relations. These were linear with a slope conductance for outward current
      of 8-11 pS. Because of the clustering of single-channel openings, detailed
      voltage dependence of kinetics and probability of opening were not studied.

PMID- 1381663
TI  - Mode of antibacterial action of dodine (dodecylguanidine monoacetate) in
      Pseudomonas syringae.
AB  - Treatment of Pseudomonas syringae cells with 50 microM dodecylguanidine
      monoacetate (dodine) resulted in the rapid degradation and release of RNA and
      cell lysis. Higher concentrations resulted in a progressive decrease in the
      intensity of these responses, and the appearance of extensive zones of coagulated
      cytoplasm, indicating that the decrease in RNA degradation probably resulted from
      an inhibition of the RNases, due to protein denaturation. Dodine also induced
      expansion of the outer membrane, with the formation of protuberances and
      intracellular myelin-like structures, which were already evident after 1 min of
      treatment, indicating that dodine is able to cross the outer and cytoplasmic
      membranes rather rapidly, and to form, alone or in combination with cell
      phospholipids and proteins, considerable amounts of triple-layered profiles. In
      P. syringae cells, saturation levels of dodine corresponded to more than five
      times the amount needed to form a close-packed monolayer of dodine on the cell
      surface. The different membranous structures formed in dodine-treated cells, and
      the coagulation of the cytoplasm, seem to be responsible for the uptake of such
      high amounts of dodine. The uptake isotherm was essentially Langmuirian. The
      results presented in this and previous reports indicate that the antibacterial
      activity of dodine on P. syringae is mainly the result of the action of micelles
      of the surfactant.

PMID- 1381664
TI  - Substance-P-like immunoreactive amacrine cells in the adult and the developing
      rat retina.
AB  - Substance-P-like immunoreactivity (SP-LI) cells in the Long-Evans rat retina were
      investigated by combining immunohistochemistry with [3H]thymidine
      autoradiography. Two subpopulations of SP-LI amacrine cells, with cell bodies in
      either the proximal portion of the inner nuclear layer (INL) or the ganglion cell
      layer (GCL), were identified based on morphology, pattern of distribution and
      development. In the INL, SP-LI cells were found scattered throughout the retina.
      However, in the GCL, they were limited to the superio-temporal region. Such a
      contrast in distribution specific to nuclear layers was present upon first
      detection of SP-LI amacrine cells and persisted throughout development.
      Birthdating revealed a temporal lag in the histogenesis of SP-LI cells situated
      in the GCL relative to that in the INL, suggesting that the two subpopulations
      developed separately. Overall, unique anatomical features of the SP-LI amacrine
      cells in the rat retina were observed which could only have been uncovered
      through detailed analyses in the adult as well as during postnatal development.

PMID- 1381665
TI  - alpha-fetoprotein and screening markers of congenital disease.
AB  - Alpha-fetoprotein (AFP) is produced in the gut and liver during fetal life and
      appears to act like albumin in the adult. Because AFP appears in the maternal
      circulation during pregnancy, interest has been focused on its measurement in
      maternal serum to predict fetal abnormality. In addition, AFP, as an embryonic
      product, is elevated in certain malignant states. This article provides a summary
      of current clinical knowledge of AFP and its applications.

PMID- 1381666
TI  - Serum concentrations of immune parameters during acute cardiogenic pulmonary
      edema.
AB  - OBJECTIVE: To evaluate the effect of acute cardiogenic pulmonary edema on the
      concentrations of immune parameters in serum. DESIGN: Prospective, controlled
      study. SETTING: Medical ICU. PATIENTS: Twenty-four consecutive patients with
      acute pulmonary edema who had significant clinical improvement within 30 mins and
      did not show any evidence of either tissue damage or infection. For comparison,
      25 healthy, age-matched controls and 25 patients with mild chronic heart failure
      were also studied. INTERVENTIONS: Treatment with oxygen, nitrates, and loop
      diuretics. MEASUREMENTS: Lymphokines, acute-phase reactants, and cortisol
      concentrations were measured in serial serum and plasma samples. MAIN RESULTS:
      Serum concentrations of soluble CD-8 antigen (soluble CD-8) decreased from 928 +/
      124 (SEM) U/mL on admission to 712 +/- 112 and 579 +/- 67 U/mL after 2 and 6
      hrs, respectively (p less than .05, p less than .01), and returned to baseline
      values within 48 hrs (853 +/- 109 U/mL). Concentrations of soluble interleukin-2
      receptor increased from 721 +/- 71 to 1078 +/- 112 and 1226 +/- 128 U/mL 12 and
      36 hrs, respectively, after admission (p less than .05, p less than .01). Plasma
      cortisol concentrations were markedly increased on admission (56.9 +/- 4.7 vs.
      13.1 +/- 1.3 micrograms/dL after recovery, p less than .001). Increased cortisol
      concentrations coincided with the nadir of soluble CD-8. Tumor necrosis factor
      alpha remained within normal limits in all patients. Neither acute-phase
      reactants nor angiotensin converting enzyme activity showed significant changes
      during the observation period. CONCLUSION: The present results indicate
      significant alterations in the serum concentrations of immune parameters as an
      effect of an uncomplicated acute cardiogenic pulmonary edema.

PMID- 1381667
TI  - Effect of bicarbonate on intracellular potential of rabbit ciliary epithelium.
AB  - Extracellular HCO3- hyperpolarizes the intracellular potential and makes the
      aqueous medium negative with respect to the stromal surface of the rabbit ciliary
      epithelial syncytium. The bases for these observations have been unclear. We have
      been studying the bicarbonate-induced hyperpolarization (BIH) with sustained
      intracellular recordings for periods as long as 1-2 hrs. The BIH was observed
      [6.0 +/- 0.4 mV (mean +/- SE, N = 22)] even when the external pH was clamped
      constant by appropriately changing the CO2 tension. External HCO3- was required
      since aeration with CO2 at low external pH did not replicate the BIH. DIDS [4,4'
      diisothiocyano-2,2'-disulfonic acid] did not abolish the effect. The
      hyperpolarization is unlikely to reflect the pH dependence of K+ channels alone,
      since the effect was not reduced by either 2 mM Ba2+ alone or 2 mM Ba2+ together
      with 50-100 microM quinidine. The BIH depends directly or indirectly on external
      Na+, since the sign of the polarization response was reversed either by replacing
      Na+ with N-methyl-D-glucamine or by blocking the Na+,K(+)-exchange pump with 50
      100 microM ouabain. Replacement of external Cl- with NO3- or application of the
      Cl(-)channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)-benzoate] depolarized
      the membrane and reversed the sign of the BIH. The response of the ciliary
      epithelium to HCO3- is complex and may arise from several mechanisms. We suggest
      that one important element is an anion channel whose conductance is reduced by
      bicarbonate and whose reversal potential is indirectly dependent on the
      operations of the Na+,K(+)-pump and a Cl(-)-linked symport.

PMID- 1381668
TI  - Differential expression of basal and hydrocarbon-induced cytochrome P-450
      monooxygenase and quinone reductase activities in subpopulations of murine
      epidermal cells differing in their stages of differentiation.
AB  - The activities of NAD(P)H-dependent quinone reductase (QR) and the cytochrome P
      450 monooxygenases 7-ethoxycoumarin O-deethylase (7-ECD) and 7-ethoxyresorufin O
      deethylase (7-ERD) were measured in four subpopulations of murine epidermal
      keratinocytes (MKs) that differed in their stages of differentiation. Noninduced
      per cell 7-ECD and 7-ERD activities were the lowest in basal cell MKs and
      progressively increased as the MKs underwent differentiation. In contrast,
      noninduced per cell QR activities in the three less differentiated MK
      subpopulations were very similar to one another and greater than the activities
      measured in the most differentiated subpopulation. Treatment of dorsal skin with
      100 nmol of dibenz[a,c]anthracene (DB[a,c]A) increased CYPIA1 mRNA abundance and
      elevated 7-ERD activities to similar per cell levels in all MK subpopulations.
      This was achieved by differential inductions (200- to greater than or equal to
      1850-fold) of 7-ERD in the different subpopulations. In contrast, QR induction by
      DB[a,c]A was similar (less than 3-fold) in all MK subpopulations. Consequently,
      the expressions of noninduced QR and 7-ERD activities in skin are regulated as a
      function of MK differentiation. However, the distributions of the noninduced
      activities of these two enzymes in MK subpopulations are the exact opposite.
      Furthermore, the relative inducibility of 7-ERD, but not QR, in skin is also
      regulated as a function of epidermal differentiation.

PMID- 1381669
TI  - Dependence of presaccadic cortical potentials on the type of saccadic eye
      movement.
AB  - Premovement cortical potentials were studied with 4 types of saccadic eye
      movement: (a) visually triggered saccades of normal reaction time (RT; regular
      saccades); (b) visually triggered saccades of extremely short RT (express
      saccades); (c) saccades towards predicted target locations (anticipatory
      saccades); (d) saccades back towards predicted location of fixation point
      (refixation saccades). With all 4 saccade types a "presaccadic negativity" with
      the maximum at the vertex (Cz) was observed. A bilaterally symmetrical component
      contained in this potential (being smallest with almost unconsciously performed
      refixation saccades and smaller in trained than in naive subjects) appeared to be
      related mainly to the subjects' volitional effort. In addition, anticipatory and
      refixation saccades were preceded by an early, widespread contralateral
      negativity, which we relate to cortical activities that prepare, in general
      terms, action within or towards the hemifield containing the saccade goal. During
      the 60 msec before anticipatory saccades, a negativity occurred over the
      contralateral central lead, which may reflect neural activation in the frontal
      eye field (FEF) and premotor cortex. In contrast, regular saccades were preceded
      30 msec before onset by a negativity over the contralateral parietal cortex,
      which probably reflects an activation of parietal visuo-motor neurons. No
      lateralization of the cortical potentials was observed before express saccades,
      which suggests that these saccades are generated in a reflex-like way mainly by
      subcortical mechanisms.

PMID- 1381670
TI  - Cortical somatosensory magnetic responses in multiple sclerosis.
AB  - Somatosensory evoked magnetic fields (SEFs) to contralateral median and ulnar
      nerve stimulation were analyzed in 10 patients with multiple sclerosis and in 8
      healthy controls. SEFs were recorded with a 24-channel SQUID gradiometer over
      both hemispheres. Seven patients showed abnormally large-amplitude SEF
      deflections at 60-80 msec; 5 of them had multiple lesions around lateral
      ventricles in magnetic resonance imaging. In 2 patients with plaques at the level
      of 3rd and 4th ventricles and medulla, the 30 msec responses were enlarged. The
      equivalent sources of 20 msec and 30-80 msec responses were in the primary hand
      sensorimotor cortex both in patients and in control subjects. The results suggest
      that early and middle-latency SEFs reflect parallel processing of somatosensory
      input. Recording of middle-latency evoked responses, electric or magnetic, may
      give additional information about the somatosensory function in multiple
      sclerosis.

PMID- 1381671
TI  - Chemosensory event-related potentials in the investigation of interactions
      between the olfactory and the somatosensory (trigeminal) systems.
AB  - The aim of the study was to investigate the interaction of the olfactory and
      somatosensory systems in the perception of chemical stimuli. Stimuli were chosen
      so as to selectively activate the olfactory (hydrogen sulphide, H2S) and
      trigeminal (carbon dioxide, CO2) nerves. In addition, carvone was included as a
      stimulus with mixed properties. Thirty healthy volunteers participated in the
      experiments. Subjects rated the intensity of each of the stimulants when
      presented alone and as a component of binary mixtures. Chemosensory event-related
      potentials (CSERPs) were obtained from 5 recording positions. Analysis of the
      intensity ratings indicated that there was no difference between the 3 stimulants
      when used as single components. In binary mixtures intensity estimates of H2S
      were suppressed by CO2 and carvone. In addition, while estimates of CO2 were
      suppressed by carvone estimates of the latter were enhanced in the same mixture.
      CSERP data confirmed earlier findings with regard to the topographic distribution
      of amplitudes, i.e., if the olfactory system had been activated largest
      amplitudes were observed at position Pz, whereas activation of the trigeminal
      nerve produced largest amplitudes at Cz. Moreover, the suppression of CO2
      estimates by carvone was reflected in a corresponding suppression of the CSERP
      amplitudes. In addition, when CO2 was mixed with H2S or carvone there was a
      decrease in the CSERP latency indicating interactions of both sensory systems in
      the time domain.

PMID- 1381672
TI  - Evidence for terminal decline in the event-related potential of the brain.
AB  - Precipitous decline (terminal decline) characterizes changes in the elderly just
      prior to death. The neurological and temporal parameters of terminal decline are
      not defined. The present study compared sensitive changes in the brain event
      related potential (ERP) in 7 subjects who died within 1 year of evaluation with
      matched controls. Cross-correlation of annual ERPs revealed disorganization
      within and between subjects in response to memory dependent conditions but not in
      response to a novel stimulus (oddball). Motor reaction time to targets was not
      sensitive to decline. The changes associated with impending death were restricted
      to decline in reliability of the ERP within 1 year of death.

PMID- 1381673
TI  - A 10 Hz "alpha-like" rhythm in the visual cortex of the waking cat.
AB  - Rhythms at about 10 Hz were recorded from the primary visual cortex of the cat
      (anterior part of area 18), with characteristics close to those of the alpha
      rhythm in man: frequency band (7-14 Hz), localization and reactivity to visual
      stimulation. Coherence analysis of this activity with the "mu" rhythms on the
      somatosensory cortex showed that although both types develop in the same overall
      behavioural situations (quiet waking and/or expectancy of an event to occur),
      they are independent.

PMID- 1381674
TI  - Single photon emission computed tomography study of subclinical rhythmic
      electrographic discharge in adults.
AB  - Subclinical rhythmic electrographic discharge in adults (SREDA) is considered a
      benign EEG pattern of uncertain significance, although it may closely resemble an
      EEG seizure pattern. We investigated a 57-year-old man with a very lateralized
      epileptiform activity localized to the occipito-temporal areas of the right
      hemisphere. Neuropsychological tests, clonazepam injection and 99m Tc-HMPAO-SPECT
      were performed during the SREDA and compared to the interparoxysmal data,
      providing further evidence that SREDA cannot be considered as an epileptic
      pattern and that, in some instances, it may be related to chronic
      hypoxic/ischemic mechanisms.

PMID- 1381675
TI  - Isotope archaeology: reading the past in metals, minerals, and bone.
AB  - The latest edition of the Oxford Dictionary (1989) defines archaeology as '...
      the scientific study of the remains and monuments of the prehistoric period'. It
      is not surprising, therefore, that modern archaeology draws as much as possible
      on scientific methods of investigation developed in other fields. In the last ten
      years the powerful method of quantitative isotope analysis has brought a new
      dimension to the examination of archaeological finds.

PMID- 1381676
TI  - Kinase inhibition by a phosphorylated peptide corresponding to the major insulin
      receptor autophosphorylation domain.
AB  - We studied the inhibitory effect of non-phosphorylated and triphosphorylated
      synthetic peptides, corresponding to amino acids 1143-1155 of the insulin
      proreceptor (domain 1151) on autophosphorylation and kinase of the insulin
      receptor. Tyrosine-phosphorylated peptides were synthesized using the N-(9
      fluorenylmethoxycarbonyl)-O-dibenzylphosphono-L- tyrosine. The triphosphorylated
      peptide (1151-P3) and the non-phosphorylated peptide (1151-NP), respectively,
      inhibited insulin receptor autophosphorylation by 65% and 70%, in a dose
      dependent and additive manner. When the receptor was pre-phosphorylated for 1 min
      with [gamma-32P]ATP, 1151-P3 decreased autophosphorylation to 60% of maximum,
      whereas 1151-NP had no further effect. In both non-activated and preactivated
      receptors, 1151-P3 inhibition of receptor autophosphorylation was prevented by
      adding 2 mM vanadate. Kinase activity towards exogenous substrate poly(Glu4, Tyr)
      was dose-dependently inhibited by both analogues. This effect was independent of
      the state of receptor phosphorylation or the addition of vanadate. Since 1151-P3
      inhibited the exogenous kinase without altering receptor endogenous
      autophosphorylation after the addition of vanadate, we investigated 1151-NP and
      1151-P3 competition for the phosphorylation of a resin-immobilized 1151 peptide.
      While 1151-NP (at 2 mM) was highly competitive, inhibiting phosphate
      incorporation by 70%, 1151-P3 caused a four-fold increase in the phosphorylation
      of 1151-NP--resin. The receptor underwent conformational changes during
      autophosphorylation and an antibody directed against a peptide corresponding to
      amino acids 1314-1330 of the proreceptor (1322Ab) was previously shown to
      immunoprecipitate specifically the non-phosphorylated receptor forms.
      Nevertheless, the 1322Ab immunoprecipitated a fully autophosphorylated receptor
      in the presence of 1151-NP, but not of 1151-P3, thus suggesting a conformational
      change induced by the non-phosphorylated peptide. In conclusion, kinase
      inhibition was still observed after the addition of phosphate groups to three
      1151-peptide tyrosines, but the peptide effect on receptor autophosphorylation,
      phosphorylation of homologous 1151-NP--resin and conformational changes induced
      in the receptor was altered dramatically. These data may provide a basis for
      further understanding the role of tyrosine phosphorylation in insulin receptor
      kinase activation or regulation.

PMID- 1381677
TI  - Glutamatergic regulation of histamine release from rat hypothalamus.
AB  - A microdialysis method was used to study the effects of glutamate on the in vivo
      release of histamine from the anterior hypothalamic area of rats anesthetized
      with urethane. Infusion of 1 mM glutamate through a microdialysis probe increased
      histamine release to about 150% of the basal release. Infusion of N-methyl-D
      aspartate (NMDA, 0.1 mM) caused a similar increase. Glutamate-evoked histamine
      release was completely blocked by D-(-)-2-amino-5-phosphonopentanoic acid (AP5,
      0.1 mM), a specific antagonist of NMDA receptors. AP5 alone also reduced
      histamine release to about 60% of the basal level. Infusion of tetrodotoxin (100
      nM) reduced histamine release to about 30% of the basal release, but had no
      effect on glutamate-evoked release. These results clearly indicate that glutamate
      enhances histamine release through NMDA receptors located on histaminergic nerve
      terminals, and suggest that there is a tonic glutamatergic regulation of this
      release.

PMID- 1381678
TI  - Effect of resiniferatoxin on the isolated rabbit iris sphincter muscle:
      comparison with capsaicin and bradykinin.
AB  - The effect of resiniferatoxin on the isolated iris sphincter muscle of the rabbit
      was compared with the effects of capsaicin and bradykinin. The three compounds
      all contracted the sphincter muscle in a concentration-dependent manner. The
      contractions were inhibited by spantide II, a tachykinin antagonist. The
      concentration-response curve of resiniferatoxin was biphasic, yielding two EC50
      values, one about 10,000 times lower than the other, the latter value being
      similar to that for capsaicin. The responses to resiniferatoxin, capsaicin or
      bradykinin were progressively reduced upon repeated application. The contraction
      evoked by either of the three compounds was not affected by thiorphan (an
      enkephalinase inhibitor) or captopril (an angiotensin-converting enzyme
      inhibitor). Pretreatment with capsaicin concentration dependently reduced the
      contractile response to a subsequent application of resiniferatoxin and vice
      versa. Bradykinin pretreatment reduced the resiniferatoxin response by about 50%;
      resiniferatoxin pretreatment completely abolished the response to bradykinin.
      Also, the contractile response to electrical stimulation was reduced
      concentration dependently by resiniferatoxin, capsaicin and bradykinin
      pretreatment. The response to electrical stimulation could be completely
      abolished by pretreatment with large doses of resiniferatoxin or capsaicin;
      pretreatment with large doses of bradykinin reduced the response by about 50%.
      Pretreatment with high concentrations of resiniferatoxin, or capsaicin, but not
      bradykinin, reduced the contractile response to the NK1 receptor agonist, [Sar9,
      Met(O2)11]SP (10(-8) M). The results suggest that the three compounds produce
      tachyphylaxis, mainly through partial (bradykinin) or complete (capsaicin,
      resiniferatoxin) exhaustion of the neuronal pool of releasable tachykinins
      although desensitization of tachykinin receptors may also contribute.

PMID- 1381679
TI  - Interleukin-6 (IL-6) gene expression and secretion by cytokine-stimulated human
      retinal pigment epithelial cells.
AB  - Retinal and choroidal inflammatory lesions are important causes of visual loss,
      but the mechanisms regulating intraocular inflammation remain poorly understood.
      By virtue of its position at the blood-retina barrier, the retinal pigment
      epithelium (RPE) cells may be critical to the initiation and propagation of
      ocular inflammation. Previously we showed that cytokine-stimulated RPE cells
      produce interleukin-8, a well-defined chemotactic factor for neutrophils and
      lymphocytes. In this study, we found that human RPE cells stimulated by human
      recombinant interleukin-1-beta (rIL-1 beta) or tumor necrosis factor-alpha (rTNF
      alpha) produce interleukin-6 (IL-6). Using a plasmacytoma proliferation assay,
      significant levels of IL-6 were found in media of RPE cells stimulated with
      either rIL-1 beta or rTNF-alpha for 4 hr. Progressive accumulation of IL-6 in
      media overlying stimulated RPE cells occurred over the subsequent 20 hr. IL-1
      beta was a significantly more potent stimulator of RPE IL-6 production than TNF
      alpha, RPE IL-6 production in response to each of these cytokines was also dose
      dependent over a range of 20 pg to 20 ng ml-1. Specific anti IL-6 antibody, but
      not control immunoglobulin, neutralized RPE-derived IL-6 activity in the
      plasmacytoma proliferation assays. RPE IL-6 mRNA levels were detectable 1 hr
      after cytokine stimulation, plateaued within 8 hr in 24-hr assays, and
      demonstrated dose-dependent kinetics in 6 hr assays. Lipopolysaccharide failed to
      induce RPE IL-6 mRNA expression or RPE IL-6 production.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1381680
TI  - Hypertonic stress induces alpha B-crystallin expression.
AB  - Alpha B-crystallin, a major lens protein, was induced in primary cultures of dog
      lens epithelial cells and glomerular endothelial cells when they were grown under
      conditions of hypertonic stress. With Western blot analysis using a specific
      alpha B-crystallin antibody, we observed a significant increase in the
      concentration of alpha B-crystallin protein in cells grown for 4-6 days in media
      supplemented with 150 mM NaCl or 250 mM cellobiose. These supplements increased
      the osmolarity of the medium from 300 to 550-600 mosmol kg-1. Alpha B-crystallin
      mRNA was also increased reaching a maximum four-fold increase in lens and 16-fold
      increase in kidney cells within 1-2 days. These studies demonstrate a type of
      regulation of alpha B-crystallin expression in cells from lenticular and non
      lenticular tissues.

PMID- 1381681
TI  - An in situ perfused guinea-pig eye model for blood-ocular transport studies:
      application to amino acids.
AB  - A technique for in situ vascular eye perfusion (VEP) in the guinea-pig has been
      developed for measurements of the blood-ocular transport kinetics of substrates
      under controlled conditions of arterial inflow. The blood-aqueous and blood
      vitreous barriers remained intact to the vascular space marker [3H]dextran (MW 70
      kDa) with the perfusion pressure maintained between 80 and 100 mmHg. Several 3H-,
      14C- or 35S-labeled amino acids, and 3H- or 14C-labeled sucrose (extracellular
      space marker) were used to validate the VEP model for transport kinetic studies.
      Multiple time-point graphic analysis was used to estimate the compartmental
      unidirectional blood-ocular transport constants, K(in), within the 20 min period
      of the VEP experiment. Blood-to-aqueous humor K(in) values for [3H]serine, [14C]N
      methyl-alpha-aminoisobutyric acid (MeAIB) and [3H] or ]14C]sucrose were 3.57 +/-
      0.38, 1.21 +/- 0.13 and 1.13 +/- 0.17 microliters min-1 g-1, respectively. The
      respective blood-to-lens K(in) values for labeled serine, MeAIB and sucrose were
      1.71 +/- 0.19, 0.09 +/- 0.03 and 0.03 +/- 0.002 microliters min-1 g-1. The uptake
      of newly secreted amino acids from the aqueous humor in the lens followed the
      order: [35S]methionine greater than [3H]serine greater than or equal to
      [35S]cysteine greater than or equal to [3H]alanine greater than [14C]cycloleucine
      greater than or equal to [14C]MeAIB greater than or equal to [3H] or
      [14C]sucrose. The data indicate lack of a rapid blood-to-lens uptake of two model
      amino acids defining the A and L amino acid carriers.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1381682
TI  - Photoreceptor-specific mRNAs in mice carrying different allelic combinations at
      the rd and rds loci.
AB  - Several retinal mRNAs encoding photoreceptor-specific proteins have been examined
      in congenic lines of mice carrying different allelic combinations at the rd and
      rds loci, to determine how mRNA expression is affected by the presence of both
      the rd and rds genes together or by the presence of one or two rd and rds alleles
      in the visual cells. Slot blots with retinal RNA from 9 to 30 days old C3H +/+,
      +/+; rd/+, +/+; rd/rd, +/+; +/+, +/rds; +/+, rds/rds; and the rd/rd, rds/rds
      double homozygous mutant mice were hybridized successively to several [32P]cDNA
      probes encoding proteins involved in phototransduction. The increases and
      decreases in the levels of mRNA coding for opsin, the alpha-subunit of
      transducin, 48 kDa protein and the beta-subunit of cGMP-phosphodiesterase in the
      heterozygous and homozygous rds and rd mouse retinas reflected the growth and
      degeneration of the photoreceptor cells. The heterozygous rd mouse (rd/+, +/+)
      retina expressed cGMP-phosphodiesterase beta mRNA levels halfway between those in
      the control (+/+, +/+) and homozygous (rd/rd, +/+) mice, indicating a possible
      dosage effect. The double homozygous mutant (rd/rd, rds/rds) showed intermediate
      levels between those observed in the two homozygotes for all mRNAs studied,
      suggesting a possible interaction between the rd and rds genes.

PMID- 1381683
TI  - Cl- transport in frog retinal pigment epithelium.
AB  - Cl- transport across the retinal membrane of the frog retinal pigment epithelium
      was studied by means of double-barrelled Cl- selective microelectrodes. Three
      types of experiments were performed. In the first group of experiments, the ionic
      dependence of Cl- influx across the retinal membrane was studied. The
      intracellular Cl- activity was first decreased by perfusing the retinal side of
      the epithelium with low Cl- solutions (3.6 mM Cl-); then the perfusate was
      changed to high Cl- solutions (90.1 mM), and the resulting Cl- influx was
      studied. In these experiments, the combined presence of extracellular Na+ and K+
      was a necessary condition for Cl- influx across the retinal membrane. This
      supports the hypothesis of Na+,K+,Cl- co-transport across this membrane. In a
      second group of experiments, the effect of furosemide was studied. Furosemide
      (100 microM) inhibited Cl- influx when the retinal extracellular Cl-
      concentration was increased from 3.6 to 90.1 mM. When administered to cells in
      steady state, furosemide in concentrations between 5 and 1000 microM decreased
      the intracellular Cl- activity. Michaelis-Menten analysis yielded a Ki for
      furosemide of 7 +/- 2 microM. The effect of furosemide on the intracellular Cl-
      activity required the combined presence of extracellular Na+ and K+. When the
      retinal extracellular K+ concentration was increased to between 0 and 10 mM, the
      furosemide-sensitive Cl- influx across the retinal membrane increased. Michaelis
      Menten analysis yielded a half maximal stimulation at an extracellular K+
      concentration of 0.5 mM. Stimulation of the epithelium with 1 mM cAMP and 0.5 mM
      IBMX reduced the effect of furosemide on the intracellular Cl- activity by 26%.
      In a third group of experiments, the effect of transepithelial currents on the
      intracellular Cl- activity was investigated. Currents that depolarized the
      choroidal membrane potential increased the intracellular Cl- activity; currents
      that hyperpolarized this membrane potential decreased the intracellular Cl-
      activity. These findings are compatible with conductive Cl- transport across the
      choroidal membrane. The apparent Cl- conductance of this membrane was estimated
      to be 0.59 mS cm-2. This represents 27% of the total conductance in the choroidal
      membrane. Administration of 1 mM cAMP and 0.5 mM IBMX caused a 21% increase in
      the apparent Cl- conductance of the choroidal membrane.

PMID- 1381684
TI  - The influence of age and chronic restricted feeding on protein synthesis in the
      small intestine of the rat.
AB  - Rates of protein synthesis (measured in vivo) and growth of the small intestine
      were studied as a function of age in ad libitum fed (control) and chronic dietary
      restricted rats. At weaning, the fractional rates of synthesis in the mucosal and
      muscularis externa and serosal layers of the small intestine of control animals
      were similarly high (90-100% per day). Although these rates subsequently declined
      with age in the muscularis externa and serosa, they remained constant in the
      mucosa. Restricted feeding (50% reduced intake), when imposed from weaning
      onwards, significantly extends the maximum life span of rodents. However, the
      change in nutritional status slows the accumulation of protein, RNA, and DNA in
      both layers of the small intestine. Although underfeeding did not prevent the age
      related fall in muscularis externa and serosal protein synthesis, significantly
      higher rates (both fractional and per ribosome) were found when compared age for
      age with controls. Mucosal fractional synthetic rates were similarly increased by
      the reduced food intake. These changes in protein turnover in the small intestine
      are consistent with the higher rates of whole body turnover previously observed
      in chronically underfed rats.

PMID- 1381685
TI  - Anatomical and functional compartmentalization of the subparafascicular thalamic
      nucleus in the rat.
AB  - The localization and the transmitter phenotype of subparafascicular thalamic
      nucleus (Spf) neurons projecting to the inferior colliculus (IC) and to the
      spinal cord (Sp) were studied by using a retrograde fluorescent double labeling
      technique, and a combined technique of retrograde tracing and
      immunohistochemistry for tyrosine hydroxylase (TH) and glutamate decarboxylase
      (GAD). The cell population of Spf-IC neurons was totally differentiated from that
      of Spf-Sp neurons which have been reported to be dopaminergic. The former were
      densely distributed, small to medium sized cells and localized in the central
      portion of the Spf, while the latter were sparsely distributed, large cells and
      localized in the marginal portion of the Spf. Spf-IC neurons were completely
      devoid of TH immunoreactivity and, instead, approximately half of them showed GAD
      immunoreactivity. From these findings, it is concluded that the Spf is distinctly
      compartmentalized by the presence at least two separate neuronal subpopulations,
      which are distinguishable in terms of their cell size, distribution patterns,
      transmitter phenotypes and trajectories.

PMID- 1381687
TI  - Operative bypass for incurable cancer of the head of the pancreas.
AB  - A series of 83 patients with incurable cancer of the pancreatic head were
      analysed. Obstructive jaundice required surgical intervention in all of them.
      Different biliary decompression operations, either single or with concomitant
      prophylactic gastro-enterostomy were constructed in different ways. From our
      study we conclude: a single bypass, using the gallbladder and anastomosed with
      the jejunum is preferred in those cases where life expectation is estimated to be
      less than 3 months. Delayed gastric emptying after gastro-enterostomy is a
      frequent complication. Double bypasses are recommended only in those cases where
      duration of life is estimated at more than 3 months.

PMID- 1381686
TI  - Perturbation of cellular energy state in complete ischemia: relationship to
      dissipative ion fluxes.
AB  - Loss of cellular ion homeostasis during anoxia, with rapid downhill fluxes of K+,
      Ca2+, Na+ and Cl-, is preceded by a slow rise in extracellular K+ concentration
      (Ke+), probably reflecting early activation of a K+ conductance. It has been
      proposed that this conductance is activated by either a rise in intracellular
      calcium concentration (Cai2+), or by a fall in ATP concentration. In a previous
      study from this laboratory (Folbergrova et al. 1990) we explored whether the
      early activation of a K+ conductance could be triggered by a rise in Cai2+. To
      that end, labile metabolites and phosphorylase a, a calcium sensitive enzyme,
      were measured after 15, 30, 60 and 120 s of complete ischemia ("anoxia"). In the
      present study, we investigated whether brief anoxia is accompanied by changes in
      ATP/ADP ratio, or in the phosphate potential, which could cause activation of a
      K+ conductance. To provide information on this issue, we added a group with 45 s
      of anoxia to the previously reported groups, and derived changes in intracellular
      pH (pHi). This allowed calculations of the free concentrations of ADP (ADPf) and
      AMP (AMPf) from the creatine kinase and adenylate kinase equilibria, and hence
      the derivation of ATP/ADPf ratios. In performing these calculations we initially
      assumed that the free intracellular Mg2+ concentration remained unchanged at 1
      mM. However we also explored how a change in Mgi2+ of the type described by
      Brooks and Bachelard (1989) influenced the calculation. The results showed that
      ADPf must have risen to 150-200% of control within 15 s, and to 330-350% of
      control within 45 s of anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381689
TI  - Intrauterine pregnancy in a patient with a sole remaining tube after local
      treatment of tubal pregnancy with hyperosmolar glucose.
AB  - A spontaneous IUP occurred 8 months after laparoscopic instillation of
      hyperosmolar glucose solution into a tubal pregnancy in a patient with a sole
      remaining tube. This is the first unequivocal proof of intact tubal function
      after treatment of a tubal pregnancy with local hyperosmolar glucose.

PMID- 1381688
TI  - The effect of estrogen level on glucose-induced changes in serum insulin-like
      growth factor binding protein-1 concentration.
AB  - OBJECTIVE: To investigate the regulation of insulin-like growth factor binding
      protein-1 (IGFBP-1) concentration during ovarian stimulation. DESIGN: A
      prospective study of patients undergoing in vitro fertilization treatment.
      SETTING: Infertility unit at the University Central Hospital of Oulu, a tertiary
      referral center. PATIENTS: Sixteen healthy, regularly menstruating lean tubal
      infertility patients. INTERVENTIONS: Oral glucose tolerance test was performed
      first in a hypoestrogenic state after suppression by long-term gonadotropin
      releasing hormone (GnRH) agonist and, second, in a hyperestrogenic state after
      stimulation by human menopausal gonadotropins. MAIN OUTCOME MEASURES: Serum
      concentrations of IGFBP-1, insulin-like growth factor I (IGF-I), insulin and sex
      hormone-binding globulin were measured before and 2 hours after glucose
      administration. RESULTS: Before and after glucose administration, the serum IGFBP
      1 concentrations were significantly higher in the hyperestrogenic state
      (estradiol [E2] level 3.5 +/- 0.57 nmol/L) after ovarian stimulation than in the
      GnRH-analogue-induced hypoestrogenic state before the gonadotropin treatment (E2
      level 0.10 +/- 0.02 nmol/L). On both occasions glucose-induced hyperinsulinemia
      caused a significant decrease in the circulating IGFBP-1 levels, whereas the IGF
      I levels remained unchanged. There was a significant correlation between E2 and
      the insulin-suppressed IGFBP-1 level. The sum of follicular diameters correlated
      positively with the serum IGFBP-1 concentration. CONCLUSIONS: Gonadotropin
      induced hyperestrogenism is related to elevated serum IGFBP-1 levels, either via
      estrogen-stimulated synthesis or via increased contribution from multiple
      follicles. Glucose-induced hyperinsulinemia suppresses serum IBFBP-1
      concentration equally both in the hypoestrogenic and hyperestrogenic states.
      Because of similar IGF-I levels, it is likely that the biological activity of IGF
      I is different before and after gonadotropin stimulations.

PMID- 1381691
TI  - Nitric oxide as a secretory product of mammalian cells.
AB  - Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to
      mediate both servoregulatory and cytotoxic functions. This article reviews how
      different forms of nitric oxide synthase help confer specificity and diversity on
      the effects of this remarkable signaling molecule.

PMID- 1381690
TI  - The effect of dextran on the pharmacokinetics of lignocaine during epidural
      anaesthesia.
AB  - The clinical significance of combining local anaesthetics with dextran is
      controversial. Although a number of investigators have found that dextran can
      prolong the action of local anaesthetics, others have not been able to
      demonstrate any significant change in the duration of anaesthesia. A study was
      carried out to investigate the effect of dextran on the pharmacokinetic behaviour
      of lignocaine during epidural anaesthesia in 20 adult male patients, who were
      randomly allocated to two treatment groups: group 1 (n = 10) was given lignocaine
      dextran; group 2 (n = 10) was given lignocaine-saline. The results of the study
      demonstrated that the addition of dextran to epidural lignocaine significantly
      slowed systemic absorption of lignocaine as indicated by a smaller absorption
      rate constant, a reduced peak plasma concentration (Cmax), a delayed time to
      reach Cmax. and a smaller area under the concentration-time curve. The observed
      findings suggest that dextran reduces vascular uptake of lignocaine from epidural
      space and that it may prolong the duration of action. The significance of these
      findings on systemic toxicity, dosage and onset of action of lignocaine need to
      be investigated.

PMID- 1381692
TI  - [Acute trichinosis. Epidemics of 166 cases in Delicias City, Chih. Diagnosis with
      tissue compression and staining].
AB  - The purposes of this report are: a) To show outstanding clinicopathological
      characteristics from the largest outbreak of trichinosis in Mexico. b) To
      describe a modification to the traditional trichinoscopy through the use of
      compressed muscle stained with ordinary dyes an immediate observation; we have
      called the procedure tissular compression and dyeing technique (TCDT). The
      outbreak occurred in Delicias, Chihuahua, and affected 166 inhabitants who ate a
      not well cooked pork sausage. All patients showed malaise, 85.5 percent myalgias,
      and 72.7 percent facial edema; leucocytosis was seen in 75 percent of the
      patients, 60 percent with eosinophilia. Electromyography was performed in 21
      patients in the acute phase of the illness and it was found abnormal in 85.7
      percent. Only one patient died (0.6%). From 59 patients who were considered very
      ill, muscle biopsies were taken, and the conventional histopathological study
      showed larvae in 88.1 percent. TCDT demonstrated worms in 90.3 percent out of 47
      biopsies; larvae were seen free and into muscle fibers with or without capsule
      cells. In conclusion TCDT is a simple, fast and easy reproducible procedure.

PMID- 1381694
TI  - Synthesis of unusual thick pili by Escherichia coli of EPEC serogroup O119.
AB  - Unique very thick pili were found in varying numbers on cells of five out of 11
      clinical isolates of enteropathogenic Escherichia coli belonging to the classic
      EPEC serogroup O119. They were approximately 12.5 nm in diameter, which is
      thicker than any other known E. coli pilus type. Analysis of the plasmid profiles
      of the O119 isolates showed that one strain was plasmid-free while the remainder
      contained numerous plasmids with a wide range of sizes. The thick pilus
      determinants were located on a 140-kb non-transferrable plasmid. They were not
      associated with adherence or a putative 90-kb enteroadherence factor plasmid.

PMID- 1381693
TI  - Bovine Escherichia coli of serotypes O55:H4 and O55:H21 which produce CNF2
      express P fimbriae and Vir surface antigen, respectively.
AB  - We have characterized the toxic and adhesive properties of Escherichia coli
      strains producing the second type of cytotoxic necrotizing factor (CNF2) and
      belonging to the classic enteropathogenic serogroup O55. Bovine CNF2 strains of
      serotype O55:H4 express P fimbriae as do pyelonephritic Escherichia coli that
      cause infections in humans. In contrast, strains of serotype O55:H21 which
      produce CNF2 from bovine origin possess the Vir surface antigen. One human strain
      of serotype O55:H- was positive for production of CNF2, but was negative for the
      two adhesive factors and for mannose-resistant haemagglutination.

PMID- 1381695
TI  - Comparative analysis of 23S ribosomal RNA gene sequences of Bacillus anthracis
      and emetic Bacillus cereus determined by PCR-direct sequencing.
AB  - The primary structures of the 23S ribosomal RNA genes of Bacillus anthracis and
      an emetic strain of Bacillus cereus were determined by direct sequencing of
      enzymatically amplified chromosomal DNA. The 23S rRNA gene sequences of B.
      anthracis and B. cereus were found to be almost identical and showed only two
      differences (a single nucleotide change, and a single base insertion in B.
      cereus). The feasibility of using PCR-direct sequencing for the rapid sequence
      determination of large-subunit rRNA genes is demonstrated.

PMID- 1381697
TI  - Inhibition effects of KRDS, a peptide derived from lactotransferrin, on platelet
      function and arterial thrombus formation in dogs.
AB  - KRDS (Lys-Arg-Asp-Ser), a tetrapeptide from human lactotransferrin, was tested
      for its effects in vitro on dog platelet function and in vivo on femoral arterial
      thrombus formation in dogs. KRDS inhibited ADP (8 microM)-induced platelet
      aggregation (IC50: 350 microM) and arachidonic acid (2 mM)-induced thromboxane B2
      generation (IC50: 175 microM). In addition, the thrombin (0.2 U/ml)-induced
      serotonin release was inhibited by KRDS (IC50: 525 microM) and the expression of
      alpha-granule membrane protein (GMP-140) was also inhibited (IC50: 350 microM).
      The results show that KRDS is an inhibitor for platelet aggregation and secretion
      to which the inhibition is more potent. Meanwhile, in the experiment of arterial
      thrombosis in dogs, KRDS (5 microM/kg) and 125I-SZ-51 (a monoclonal antibody
      against GMP-140) were injected before operation and immediately after the
      thrombus formation, respectively. In the KRDS group, the weight of removed
      thrombi was reduced to 50% of that in controls and the radioactivity per mg of
      labeled thrombi to 33.3% while in blood the radioactivity increased 2 times that
      in controls at the 4th hour after the injection of 125I-SZ-51. The radioactivity
      ratio between removed thrombi and blood was only 16% of that in controls. These
      results indicate that KRDS can inhibit thrombus formation in vivo and is a
      promising antithrombotic agent.

PMID- 1381696
TI  - Apolipoprotein E polymorphism in a Danish population compared to findings in 45
      other study populations around the world.
AB  - Apolipoprotein E (apoE) phenotypes were determined in a random sample of 466
      Danish men born in 1948. The frequencies of the common alleles of the apoE gene
      were (with 95% confidence intervals) epsilon 2 = 0.085 (0.068-0.105), epsilon 3 =
      0.741 (0.712-0.769), and epsilon 4 = 0.174 (0.150-0.200). These frequencies were
      compared to findings in 45 other study populations around the world (n greater
      than 100). The Danish population was found to cluster with populations from
      Iceland, Norway, Iceland, Scotland, the Netherlands, Germany, France (Paris), and
      Caucasian populations in Canada and the USA. The compiled data further show that
      dissimilarities in apoE allele frequencies among Caucasian populations are
      comparable to dissimilarities between some Caucasian and Asian populations.
      Notably, the frequency of epsilon 4 appears to be higher in northern regions of
      Europe (the Nordic countries, Scotland, Germany, and the Netherlands) than in
      southern regions (Switzerland, Tyrol, France [Nancy], Italy, and Spain).

PMID- 1381698
TI  - [Treatment of chronic hepatitis B. Part 1: Critical overview of current results
      of studies].
AB  - AIMS: Critical appraisal of presently available results of studies on the
      treatment of chronic hepatitis B. MAIN POINTS CONSIDERED: Even the controlled
      studies on the treatment of chronic hepatitis B carried out in recent years, in
      particular involving the use of interferons, possibly in combination with
      glucocorticosteroids, real methodological shortcomings that, in part, are due to
      the characteristics of chronic hepatitis, such as variations in its evolution,
      inadequate information provided by individual evolution-related parameters and
      failure to take account of patient variables. Moreover, the spontaneous evolution
      of the disease is difficult to predict, and a definitive assessment of the
      results of treatment always requires longterm follow-up. CONCLUSIONS: Despite the
      shortcomings of the individual studies, treatment with interferon represents a
      great advance in the therapy of chronic hepatitis B. However, the high percentage
      of treatment failures makes the continued search for new therapeutic modalities
      necessary.

PMID- 1381699
TI  - Evaluation of keratinolytic potential of some fungal isolates from gelatin
      factory campus.
AB  - During hair degradation, majority of organic sulphur was oxidized to inorganic
      sulphate and thiosulphate by four fungal isolates (Cylindrocarpon lichenicola,
      Graphium cuneiferum, Microsporum gypseum, and M. fulvum) from gelatin factory
      soil. Inorganic thiosulphate, an unusual metabolite, was regularly detected in
      the culture filtrates of all fungi, although in less amounts. Maximum quantity
      (44 micrograms/ml) was released by G. cuneiferum on 50th day of incubation. All
      four fungi showed significant extracellular keratinase activity on human hair.
      Sulphydryl compounds were present in low amounts throughout the experiment.
      Detection of inorganic sulphate and thiosulphate with significant release of
      total protein and keratinase and changes in alkalinity, established the role of
      sulphitolysis and peptidolysis during keratin biodegradation by fungi which
      ultimately results in complete keratin degradation.

PMID- 1381700
TI  - Anti-implantation role for substance P and neurotensin in rat.
AB  - Substance P (SP) and neurotensin (NT), two structurally related peptides with
      contrasting biological actions, have been shown to have some role in peripheral
      reproductive processes. Intrauterine microinjection of SP or NT on day 4 or 5 of
      pregnancy in the rat significantly reduced the number of viable fetuses, weight
      and glycogen content of the uterus. The number of viable fetuses, uterine weight
      or glycogen content were not modified when SP/NT was microinjected on day 8, 9,
      10 or on day 14, 15 and 16. The results indicate that the peptides possibly exert
      a direct local alteration in uterine vascular permeability causing failure in
      implantation.

PMID- 1381702
TI  - Progression of human cutaneous melanoma is associated with loss of expression of
      c-kit proto-oncogene receptor.
AB  - Mutations at the white spotting (w) locus in mice have deleterious effects on
      germ cells, melanocytes and hematopoietic stem cells. The w locus encodes the c
      kit tyrosine-kinase receptor whose ligand is the product of the SI locus. Using
      monoclonal antibodies (MAb(s)) to the extracellular domain, we have evaluated the
      expression of c-kit in normal and transformed melanocytes. This cell lineage
      synthesizes a receptor with a mw of 145 kDa. The gene product is expressed in
      epidermal melanocytes and in a fraction of nevocytic and blue nevi. In primary
      melanomas, loss of the receptor is observed in more invasive lesions. Only 30% of
      the metastatic lesions express detectable levels of the receptor. These findings
      demonstrate that the c-kit product is down-regulated in melanocytes following
      malignant transformation. The functional relevance of this modulation remains to
      be evaluated.

PMID- 1381701
TI  - G-CSF: status quo and new indications.

PMID- 1381703
TI  - The effect of endocrine therapy with medroxyprogesterone acetate, 4
      hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin-like
      growth factor (IGF)-I, IGF-II and IGFBP-1 in women with advanced breast cancer.
AB  - Tamoxifen treatment of women with advanced breast cancer has previously been
      reported to reduce plasma insulin-like growth factor-type I (IGF-I)
      concentrations. In this study we have examined the effect of treatment with
      Tamoxifen, medroxyprogesterone acetate (MPA) or 4-hydroxyandrostenedione (4-OHA)
      on plasma IGF-I and IGF-II concentrations. As IGF-binding proteins (IGFBPs) can
      modulate the biological effects of IGF-I, plasma IGFBP-I levels were also
      measured. Treatment with Tamoxifen for 2 weeks resulted in a small, but
      significant, decrease in IGF-I levels, but increase in the plasma concentration
      of IGFBP-I. In contrast, treatment with MPA increased levels of IGF-I, but
      significantly reduced plasma IGFBP-I concentrations. Treatment with 4-OHA had no
      significant overall effect on plasma IGF-I or IGFBP-I levels, although changes
      were detected for some subjects. Plasma IGF-II concentrations were not altered by
      treatment with Tamoxifen, MPA or 4-OHA. It is concluded that although treatment
      with Tamoxifen or MPA produced significant changes in plasma IGF-I
      concentrations, any physiological effects of such changes are likely to be
      modulated by the corresponding alterations in plasma IGFBP-I concentrations.

PMID- 1381704
TI  - Phenotype-specific "tissue" transglutaminase regulation in human neuroblastoma
      cells in response to retinoic acid: correlation with cell death by apoptosis.
AB  - Neuroblastomas in culture are characterized by the presence of 2 morphologically
      and biochemically distinct phenotypes (i.e., neural "N-type" and flat substrate
      adherent "S-type") which undergo transdifferentiation. Human neuroblastoma SK-N
      BE(2) cells differentiate toward a neural phenotype upon retinoic acid (RA)
      treatment. However, we recently showed that, during the RA treatment, a subset of
      SK-N-BE(2) cells undergo apoptosis; these cells specifically express a high
      "tissue" transglutaminase (tTG) level. This study was undertaken to investigate
      the cellular and molecular basis of the action of retinoic acid on apoptosis in
      human neuroblastoma cells. As a biochemical marker of the phenomenon we studied
      the tTG gene expression in the parental line SK-N-BE(2) and in 2 clones which
      stably express neuroblastic [BE(2)-M17] and substrate-adherent [BE(2)-C]
      features, respectively. Data showed a differential phenotype-specific regulation
      of tTG gene expression. In fact, RA treatment enhanced tTG expression and
      apoptotic index in the flat substrate-adherent variant, whereas, in cells
      expressing the neural phenotype, very low tTG expression and apoptosis were
      found. Northern-blotting analysis revealed that the substrate-adherent cells had
      a basal 3-fold higher level of tTG mRNA. An increase in tTG mRNA major transcript
      levels (3.7 kb) occurred within a few hours of exposure to RA in both the
      phenotypic variants. By contrast, tTG protein level was very low in the cell
      expressing the neuronal phenotype, even after prolonged exposure to RA.
      Immunohistochemical analysis indicated that tTG protein, in addition to mature
      apoptotic cells, was specifically localized in the flat substrate-adherent
      variant both in the wild-type and in the BE(2)-C clone. These findings suggest
      that the ability to undergo apoptosis in the neuroblastoma cells is associated
      with the expression of a non-neuronal neuroectodermal (substrate-adherent cells)
      immature phenotype.

PMID- 1381705
TI  - Schedule-dependent effects of two consecutive, divided, low doses of actinomycin
      D on translocation of protein B23, inhibition of cell growth and RNA synthesis in
      HeLa cells.
AB  - The effects of 2 consecutive, divided, low doses of actinomycin-D (Act-D) on
      cellular localization of protein B23, inhibition of cell growth, RNA synthesis
      and colony formation were studied in HeLa cells. The second dose of Act-D was
      administered at various times after removal of the first dose. One short exposure
      of HeLa cells to Act-D had previously been shown to induce "reversible"
      translocation of protein B23, inhibition of cell growth, and RNA synthesis.
      Relocalization of protein B23 from the nucleoplasm to nucleoli as well as
      "reversible" inhibition of cell growth and RNA synthesis were still observed in
      cells that had been treated with a second dose of Act-D administered as early as
      0-2 hr or as late as 30 hr after removal of the first dose of Act-D. In contrast,
      no relocalization of protein B23 from the nucleoplasm to nucleoli was observed in
      cells that had been treated with a second dose of Act-D administered 9 hr after
      removal of the first dose. A second exposure to Act-D, administered 9 hr after
      removal of the first dose, caused irreversible inhibition of cell growth and RNA
      synthesis; a significant inhibitory effect on colony formation was also observed.
      RNA synthesis in HeLa cells after 2 sequential exposures to Act-D was further
      analyzed by 1% agarose gel electrophoresis. There were higher-molecular-weight
      bands above 28S RNA, which may be the 45S and 32S RNA, observed in the controls
      and in the cells that had been exposed to Act-D treatment once or in the cells
      that underwent Act-D exposure twice, in which the second dose was administered as
      early as 0-2 hr or as late as 30 hr after removal of the first dose. These high
      molecular-weight bands were not observed in the cells that underwent Act-D
      exposure twice, in which the second dose was administered 9 hr after removal of
      the first. These results indicated that cells at different stages of inhibition
      or that have recovered from the first exposure to Act-D respond differently to
      the second short Act-D exposure.

PMID- 1381706
TI  - Ovulation induction increases serum levels of insulin-like growth factor binding
      protein 1.
AB  - The effect of ovulation induction on serum insulin-like growth factor binding
      protein 1 (IGFBP-1) level in relation to sex hormone binding globulin (SHBG)
      levels was evaluated. Serum samples were collected 8 to 12 days after ovulation
      from 26 women undergoing ovulation induction with clomiphene citrate (CC), and
      from 58 women treated with CC in combination with human menopausal gonadotropin
      (hMG) and human chorionic gonadotropin (hCG). In addition, serum samples were
      obtained from 63 spontaneously ovulating women and from 12 women during an
      anovulatory cycle. Luteal phase serum IGFBP-1 levels were 4.22 +/- 2.95
      micrograms/L (P less than .05) in the CC group and 7.31 +/- 6.13 micrograms/L (P
      less than .001) in the CC/hMG/hCG group as compared to unstimulated ovulatory
      cycles (2.64 +/- 2.52 micrograms/L). No significant difference in IGFBP-1 levels
      was seen between spontaneously ovulatory and anovulatory cycles. The serum IGFBP
      1 levels correlated positively to SHBG levels (r = .52, P less than .001). The
      data show that ovulation induction increases serum IGFBP-1 levels in parallel to
      SHBG levels, indicating that ovarian stimulation, which results in increased
      steroid hormone production, also induces changes in other factors known to
      modulate steroid hormone actions.

PMID- 1381707
TI  - Immunophenotype of SV40-T gene transfected epithelial cell lines derived from
      human benign breast tumors.

PMID- 1381708
TI  - In vitro keratinization of normal human salivary gland cells.

PMID- 1381709
TI  - Receptor phenotype underlies differential response of hepatocytes and
      nonparenchymal cells to heparin-binding fibroblast growth factor type 1 (aFGF)
      and type 2 (bFGF).
AB  - Heparin-binding fibroblast growth factors (HBGF) have been implicated in the
      regeneration of both parenchymal and nonparenchymal cells of the liver. The
      response to and phenotype of hepatocyte receptors for HBGF-1 (acidic fibroblast
      growth factor) and HBGF-2 (basic fibroblast growth factor) were compared to
      keratinocytes, fibroblasts, and endothelial cells. HBGF-1 stimulated DNA
      synthesis in hepatocytes, keratinocytes, fibroblasts, and endothelial cells
      whereas activity of HBGF-2 was limited to fibroblasts and endothelial cells. HBGF
      2 antagonized the mitogenic activity of HBGF-1 for hepatocytes and keratinocytes.
      Hepatocytes and keratinocytes exhibited both high- and low-affinity, nonmatrix
      receptor sites for HBGF-1, but only low-affinity sites for HBGF-2. The
      mesenchymal cells displayed only high-affinity sites for both HBGF-1 and HBGF-2.
      Northern blot and immunochemical analysis revealed that the expression of HBGF
      receptor genes bek and flg are partitioned between normal hepatocytes and
      nonparenchymal cells, respectively. Expression of epithelial cell-specific,
      mesenchymal cell-derived HBGF-7 (keratinocyte growth factor) mRNA in regenerating
      liver tissue was undetectable relative to HBGF-1. The results support a
      multifunctional role of HBGF-1 acting through different receptor phenotypes in
      hepatocyte and nonparenchymal cells during liver regeneration.

PMID- 1381710
TI  - FK-506-binding proteins from streptomycetes producing immunosuppressive
      macrolactones of the FK-506 type.
AB  - FK-506-binding proteins (FKBPs), which in T cells are supposed to mediate the
      immunosuppressive effects of the compounds FK-506 and rapamycin, have been
      isolated from Streptomyces chrysomallus, S. hygroscopicus subsp. ascomyceticus,
      and S. hygroscopicus. The latter two strains are producers of ascomycin (the
      ethyl analog of FK-506) and rapamycin, respectively. Like the 12-kDa FKBP in
      eukaryotic organisms such as humans, bovines, and Saccharomyces cerevisiae, or
      the FKBPs from gram-positive streptomycetes are peptidyl-prolyl-cis-trans
      isomerases. Inhibition studies using FK-506, rapamycin, or ascomycin, revealed
      inhibition of the peptidyl-prolyl cis-trans isomerase activity of the proteins at
      the nanomolar level, which is in the same range as with eukaryotic FKBPs. The
      M(r)s of the various FKBPs were 13,500 to 15,000, and they had the same pI of
      approximately 4.5. The N-terminal sequences of the three FKBPs were nearly
      identical in the first 20 amino acids. The amino acid sequence deduced from the
      gene sequence of S. chrysomallus gave a polypeptide of 124 amino acids. The
      homologies to FKBPs from humans, S. cerevisiae, and Neurospora crassa were 38,
      39, and 50% identity in relevant positions, respectively. Significant homology of
      38% was also seen with the C-terminal halves of bacterial protein surface
      antigens like the Mip protein of Legionella pneumophila and the 27-kDa Mip-like
      protein of Chlamydia trachomatis. In addition, two more open reading frames in
      Pseudomonas aeruginosa and Neisseria meningitidis of unknown function show
      regions of homology to the S. chrysomallus FKBP. In contrast to fungi,
      streptomycetes are resistant to macrolactones. Ascomycin-producing S.
      hygroscopicus subsp. ascomyceticus excretes the compound almost quantitatively
      into medium, which indicates that the organism has an efficient self-protection
      mechanism against its own secondary metabolite.

PMID- 1381711
TI  - Involvement of a vitronectin-like protein in attachment of Agrobacterium
      tumefaciens to carrot suspension culture cells.
AB  - Infections of dicotyledonous plants by Agrobacterium tumefaciens result in the
      formation of crown gall tumors. Attachment of the bacteria to plant host cells is
      required for tumor formation. Human vitronectin and antivitronectin antibodies
      both inhibited the binding of A. tumefaciens to carrot cells. Wild-type bacteria
      are able to bind radioactive vitronectin; nonattaching mutants showed a reduction
      in the ability to bind vitronectin. The binding of biotype 1 A. tumefaciens to
      carrot cells or to radioactive vitronectin was not affected by high ionic
      strength. Detergent extraction of carrot cells removed the receptor to which the
      bacteria bind. The extract was found to contain a vitronectin-like protein. These
      results suggest that A. tumefaciens utilizes a vitronectin-like protein on the
      plant cell surface as the receptor for its initial attachment to host cells.

PMID- 1381712
TI  - A switch in cytokeratin expression and intermediate filament organization
      associated with epithelial stratification.
AB  - Low density gingival epithelial cells were cultured on the side of glass slides
      facing rat's tail collagen lattices. Under these conditions and in the presence
      of physiological level of calcium, colony formation was enhanced and
      stratification was slowed down. The strong attachment of the cells to glass
      slides permitted immunocytochemical examination of cytokeratin (CK) expression
      and their organization within individual cells during the different stages of
      epithelial maturation. The present results showed that during the stage of cell
      migration and colony formation, the cells express the same set of cytokeratins
      (basal cell marker 14, simple epithelial markers 8, 18 and 19, and marker of
      hyperproliferation 16) which forms a well-defined network of organized filaments.
      At the stratification stage, the filament network became dense by the additional
      expression of the markers of differentiation in non-keratinized stratified
      epithelia (CK 4 and 13). These appeared once individual cells started to overlap
      the basal cells, a period during which the cell-temporarily changed morphology.
      Whilst the suprabasal cells exhibited dense filament network labelled for CK 4
      and 13, the density of labelled filaments for CK 14, 8 and 18 was much lower,
      indicating that these cells contained newly-formed filaments lacking the basal
      and simple epithelial keratins. The simple epithelial cytokeratins became weakly
      labelled in older cultures. The uncoupling of paired expression of cytokeratins 4
      and 13 was observed in non-colony forming aged cells. This provides an example of
      altered program of cytokeratin expression during epithelial maturation.

PMID- 1381713
TI  - Insulin-like growth factor binding protein (IGFBP-3), an inhibitor of serum
      growth factors other than IGF-I and -II.
AB  - Our results show that an insulin-like growth factor binding protein, IGFBP-3,
      purified from rat serum, is an inhibitor of chick embryo fibroblast (CEF) growth.
      It abolished DNA synthesis in CEF stimulated by IGF-I as well as by human serum.
      Rat IGFBP-3 and IDF45 (an inhibitory diffusible factor secreted by mouse cells)
      had the same activities, confirming that they have an intrinsic capacity to
      inhibit serum stimulation and may be considered as growth inhibitors. Our data
      show that inhibition by IGFBP-3 of serum stimulation was not simply the result of
      its inhibition of IGF present in the serum: 1) While anti-IGF-I IgG was able to
      completely inhibit stimulation induced by added IGF-I, it did not decrease
      stimulation induced by 1% human serum. Anti-IGF-II IgG inhibited the stimulation
      induced by added IGF-II, but only 25% decreased the stimulation induced by 0.7%
      serum. The percent inhibition was not significantly increased when the
      concentration of serum was decreased to 0.2%, which induced 140% stimulation of
      DNA synthesis; 2) stimulation by 0.2% serum was much more inhibited by IGFBP-3
      than by IgG anti IGF-II; 3) after separation of IGF-I and IGF-II from serum by
      chromatography of acidified serum proteins on BioGel P150, the remaining serum
      proteins (with a molecular mass greater than 45 kDa) which were depleted in IGF-I
      and -II (verified by RIA determination) still stimulated DNA synthesis, and this
      stimulation was 80% inhibited by IGFBP-3.

PMID- 1381714
TI  - Granulocyte-macrophage colony-stimulating factor and steel factor induce
      phosphorylation of both unique and overlapping signal transduction intermediates
      in a human factor-dependent hematopoietic cell line.
AB  - Steel factor (SF), the ligand for the proto-oncogene c-kit, acts synergistically
      with GM-CSF or IL-3 to support the growth of normal human hematopoietic
      progenitor cells. We examined the effects of SF on GM-CSF or IL-3 induced
      proliferation of a human factor-dependent cell line, MO7. SF supported MO7 cell
      proliferation as well as IL-3 or GM-CSF alone, and its addition dramatically
      enhanced (three- to sixfold) maximal GM-CSF or IL-3 stimulated proliferation. SF
      did not increase the number or affinity of cell surface GM-CSF receptors. We
      examined several early events of signal transduction in an effort to elucidate
      the biochemical mechanisms of synergy of these factors. Since each of these three
      cytokines is believed to function in part through activation of a tyrosine
      kinase, we examined their effects on cellular phosphotyrosine containing
      proteins. Each cytokine induced rapid, transient, and concentration dependent
      tyrosine phosphorylation of a number of substrates. For GM-CSF and IL-3, these
      phosphoproteins were indistinguishable (150, 125, 106, 93, 80, 79, 73, 44, 42,
      and 36 kDa), while SF induced major or minor tyrosine phosphorylation of 205, 140
      150, 116, 106, 94, 90, 80, 79, 73, 44, 42, 39, 36, 32 kDa phosphoproteins. Two
      other signal transduction intermediates known to be phosphorylated and activated
      by GM-CSF and IL-3, the 70-75 kDa Raf-1 kinase, and p42 mitogen-activated protein
      kinase-2 (MAPK), were also phosphorylated by SF. Combinations of GM-CSF or IL-3
      with SF did not further increase the phosphorylation of Raf-1 or p42 MAPK when
      compared to any of the factors alone. In contrast SF, but not GM-CSF or IL-3,
      induced tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma). These
      results indicate that SF and GM-CSF/IL-3 have partially overlapping effects on
      early signal transducing events, as well as striking differences, such as
      tyrosine phosphorylation of PLC-gamma. This cell line should provide a useful
      model system to investigate the complicated process of hematopoietic growth
      factor synergy.

PMID- 1381715
TI  - Neutrophil adhesion to TNF alpha-activated endothelial cells potentiates
      leukotriene B4 production.
AB  - Since adhesion of neutrophils (PMN) to endothelial cells may influence PMN
      activation responses, we examined whether adhesion of PMN to TNF alpha-activated
      human umbilical vein endothelial cells (HUVEC) stimulates leukotriene B4 (LTB4)
      production. Endothelial adhesivity towards PMN increased after HUVEC pretreatment
      with TNF alpha for 4 h. LTB4 production increased markedly in response to
      stimulation with arachidonic acid (20 microM) when PMN were added to the
      hyperadhesive HUVEC. In contrast, stimulation of PMN in suspension did not
      potentiate LTB4 production. LTB4 production persisted when PMN were applied to
      TNF alpha-pretreated HUVEC fixed with 1% paraformaldehyde excluding the
      possibility that metabolic activity of endothelium participates in this response.
      PMN adhesion to plastic and gelatin also enhanced LTB4 indicating that adhesion
      was a critical event in inducing LTB4 production. We used monoclonal antibodies
      (mAb) to adhesion molecules on endothelial cells (i.e., endothelial leukocyte
      adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1)) or
      on PMN (CD18) to assess the role of PMN adhesion to the activated endothelium on
      LTB4 potentiation. Both anti-ELAM-1 mAb and anti-ICAM-1 mAb inhibited PMN
      adhesion (by 55 and 41%, respectively) as well as LTB4 production (by 65 and 50%,
      respectively). Anti-CD18 mAb also reduced the adhesion (65%) and the LTB4
      production (66%). Furthermore, combination of anti-ELAM-1 mAb (H18/7) and anti
      ICAM-1 mAb (RR1/1) or of anti-ELAM-1 mAb (H18/7) and anti-CD18 mAb (IB4) had an
      additive effect in inhibiting both PMN adhesion as well as LTB4 production. PMN
      adherence to immobilized recombinant soluble rELAM-1 or rICAM-1 also increased
      LTB4 production, which was prevented with relevant mAbs. However, neither rELAM-1
      nor rICAM-1 stimulated LTB4 production of PMN in suspension. We conclude that PMN
      adhesion to TNF alpha-stimulated endothelial cells enhances LTB4 production by
      PMN, a response activated by binding of PMN to expressed endothelial cell surface
      adhesion molecules.

PMID- 1381716
TI  - Current status of HIV therapy: I. Antiretroviral agents.
AB  - The clinician's armamentarium is no longer limited to zidovudine as the only
      antiretroviral agent that enhances both quality and length of life. ddI has shown
      clinical benefit in patients previously treated with zidovudine. Recently, the
      combination of zidovudine and ddC has been approved on the basis of surrogate
      marker activity; its clinical role awaits results of ongoing trials.

PMID- 1381717
TI  - Optimization of the separation of the Rp and Sp diastereomers of phosphate
      methylated DNA and RNA dinucleotides.
AB  - The separation by reversed-phase high-performance liquid chromatography of Rp and
      Sp diastereomers of phosphate-methylated DNA and RNA dinucleotides was studied
      with respect to pH, organic modifier type and concentration and reversed-phase
      packing material. Drylab G was used to deduce optimum conditions. On the basis of
      the observed discrepancies between the computer predictions and experimental
      results, the gradient operation procedure with volatile buffers was improved. By
      repetitive chromatography on a 250 x 22 mm I.D. reversed-phase column, fourteen
      diastereomeric pairs were obtained in at least 97% purity and 60% yield, in
      amounts of 10-100 mg.

PMID- 1381718
TI  - Interleukin-7 is a growth factor for Sezary lymphoma cells.
AB  - Sezary syndrome is a cutaneous T cell lymphoma characterized by infiltration of
      the skin by CD4+ cells. These cells generally respond poorly to mitogens and T
      cell activators. We have studied the action of IL1 to IL4, IL6, and IL7 on the
      proliferation of Sezary cells from 12 patients. With the exception of IL2 and
      IL7, the cytokines studied had no proliferative effect on these cells. Whereas
      IL2 had only a low proliferative capacity (two- to threefold increase) on
      peripheral blood mononuclear cells, recombinant IL7 constantly induced a very
      significant (3-40-fold increase) proliferative response, and was used
      successfully to generate cell lines in three out of eight cases. Growth of Sezary
      cell lines was shown to be strictly dependent on IL7, and after 2-5 wk of culture
      presented a switch to a homogeneous phenotype CD3+4+8-7- (except for one line
      that remained CD7+), with a typical morphology of Sezary cells. Their tumoral
      origin was demonstrated by the expression of the same T cell receptor-beta gene
      rearrangement as the patients' T cells. Importantly, cultured normal epidermal
      keratinocyte supernatants could support the growth of our Sezary lines.
      Furthermore, the proliferative activity contained in these supernatants was
      completely blocked by a monoclonal anti-IL7 antibody. These results suggest that
      IL7 may, therefore, represent an important cytokine in the physiopathology of
      cutaneous T cell lymphoma.

PMID- 1381719
TI  - Inhibition of the complement membrane attack complex by the galactose-specific
      adhesion of Entamoeba histolytica.
AB  - The human complement system is an important early host defense against infection.
      Entamoeba histolytica activates the complement system but is resistant to killing
      by complement C5b-9 complexes deposited on the membrane surface. Our aim was to
      identify components of the amebic plasma membrane that mediate resistance to
      human complement C5b-9 by screening for neutralizing monoclonal antibodies. A
      monoclonal antibody was identified that abrogated amebic resistance to C5b-9, and
      the mAb was shown to recognize the parasite's galactose-specific adhesin. The
      purified adhesin bound to C8 and C9 and conferred C5b-9 resistance to sensitive
      ameba upon reconstitution; these activities of the adhesin were inhibited by the
      antiadhesin mAb. The E. histolytica adhesin shared sequence similarities and
      antigenic cross-reactivity with CD59, a membrane inhibitor of C5b-9 in human
      blood cells, suggesting both molecular mimicry and shared complement-inhibitory
      functions.

PMID- 1381721
TI  - Molecular genetics of the cutaneous basement membrane zone. Perspectives on
      epidermolysis bullosa and other blistering skin diseases.

PMID- 1381720
TI  - Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces
      mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial
      endothelial cells.
AB  - Accumulation of monocyte-derived foam cells in focal areas of the arterial intima
      is one of the key events in early atherogenesis. We have examined the effect of
      lysophosphatidylcholine (lyso-PC; lysolecithin), a major phospholipid component
      of atherogenic lipoproteins, on the expression of adhesion molecules for
      monocytes, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular
      adhesion molecule-1 (ICAM-1), in cultured human and rabbit arterial endothelial
      cells. Cultured rabbit aortic endothelial cells treated with lyso-PC showed
      increased mRNA and cell surface expression of VCAM-1 and ICAM-1, which was
      associated with increased adhesion of monocytes and monocyte-like cells (THP-1,
      U937). In cultured human iliac artery endothelial cells, lyso-PC similarly
      induced both VCAM-1 and ICAM-1, whereas in umbilical vein endothelial cells only
      ICAM-1 was up-regulated. In all endothelial cells examined, the effect of lyso-PC
      on E-selectin (endothelial-leukocyte adhesion molecule-1) expression was
      negligible, thus differentiating this stimulus from other endothelial activators,
      such as interleukin 1, tumor necrosis factor, or lipopolysaccharide. We conclude
      that lyso-PC can selectively induce VCAM-1 and ICAM-1 in arterial endothelial
      cells and that this action, in addition to its monocyte chemoattractant activity,
      may play an important role in monocyte recruitment into atherosclerotic lesions.

PMID- 1381722
TI  - Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a
      dominant conformational epitope on human thyroid peroxidase.
AB  - To characterize the nature of thyroid peroxidase (TPO) autoantibodies present in
      the sera of patients with autoimmune thyroid disease, we cloned three IgG1/kappa
      Fab fragments which bind 125I-TPO. This was accomplished by the molecular cloning
      and expression in bacteria of IgG gene fragments from B cells infiltrating the
      thyroid of a patient with Graves' disease. The three Fab fragments (SP2, SP4, and
      SP5) are coded for by a common heavy chain (VH1, D, JH3) and three related, but
      different, light chains (VK1, JK2). The SP Fab fragments bind specifically to TPO
      with high affinities (6 x 10(-11)-2 x 10(-10) M) comparable to those of serum TPO
      autoantibodies. TPO autoantibodies represented by the SP Fab fragments are
      present in all 11 patients studied, constitute a high proportion (36-72%) of
      serum TPO autoantibodies in individual patients and interact with a
      conformational epitope on TPO.

PMID- 1381723
TI  - Extensive posttranscriptional deletion of the coding sequences for part of
      nucleotide-binding fold 1 in respiratory epithelial mRNA transcripts of the
      cystic fibrosis transmembrane conductance regulator gene is not associated with
      the clinical manifestations of cystic fibrosis.
AB  - Cystic fibrosis (CF) is a recessive hereditary disorder, requiring both parental
      cystic fibrosis conductance transmembrane regulator (CFTR) genes to carry
      mutations for clinical disease to manifest, i.e., only 50% of normal CFTR gene
      expression is required to maintain a normal phenotype. To help define the minimum
      amount of normal CFTR gene expression necessary to maintain normalcy, we have
      capitalized on our prior observation (Chu, C.-S., B. C. Trapnell, J. J. Murtagh,
      Jr., J. Moss, W. Dalemans, S. Jallat, A. Mercenier, A. Pavirani, J.-P. Lecocq, G.
      R. Cutting, et al. 1991. EMBO [Eur. Mol. Biol. Organ] J. 10:1355-1363) that
      normal individuals can have up to 66% of bronchial CFTR mRNA transcripts that are
      missing exon 9, a region representing 21% of the sequence coding for the critical
      nucleotide (ATP)-binding fold 1 (NBF1) of the predicted CFTR protein. The study
      population included 78 individuals with no prior diagnosis of CF. Evaluation of
      bronchial epithelial cells (obtained by bronchoscopy) revealed that exon 9 was
      variably deleted in all individuals. Remarkably, there were four individuals, all
      greater than or equal to 35 yr, in whom bronchial epithelial cells exhibited 73,
      89, 90, and 92% CFTR transcripts with inframe deletion of exon 9, respectively,
      despite normal sweat Cl- and no clinical manifestation of CF. In the context that
      only 8% or less of bronchial CFTR transcripts need exon 9 to maintain normal
      airway function, these observations strongly suggest that either exon 9 is not
      necessary for CFTR structure and/or function or that only a very small fraction
      of bronchial epithelial cells need to express normal CFTR mRNA transcripts with
      exon 9 to perform the function of CFTR sufficient to maintain a normal phenotype
      in vivo.

PMID- 1381724
TI  - Differential pp60c-src activity in well and poorly differentiated human colon
      carcinomas and cell lines.
AB  - The results presented in this report demonstrate increased pp60c-src kinase
      activity associated with moderate to well differentiated colon tumors,
      corroborating previous observations by other groups. Extension of this analysis
      to include a small number of poorly differentiated colon carcinomas revealed src
      kinase activity comparable to that observed in normal colonic mucosa,
      considerably less than that observed in moderate/well differentiated lesions.
      Correlations of src kinase activity with differentiation was confirmed within a
      panel of colon cell lines where increased activity, associated with moderate/well
      differentiated lines, was accompanied by increased expression of pp60c-src
      protein. Use of an antiphosphotyrosine antibody in immunoprecipitation revealed
      the presence of novel phosphotyrosyl cellular substrates in human colon cell
      lines displaying elevated pp60c-src kinase activity. These observations suggest a
      role for the src protooncogene in colonic differentiation pathways.

PMID- 1381725
TI  - Effects of interferon-gamma on nitric oxide synthase activity and endothelin-1
      production by vascular endothelial cells.
AB  - Given the pivotal role suggested for IFN-gamma in immune diseases of the vascular
      wall, we investigated the effects of IFN-gamma on nitric oxide (NO) and
      endothelin-1 (ET-1) expression in bovine aortic endothelial cells (BAEC). We have
      previously reported that TNF-alpha enhanced NO synthase activity in BAEC as
      assessed by quantifying release of bioactive NO with reporter monolayers and
      measuring conversion of L-[14C]arginine to L-[14C] citrulline. In murine
      macrophages IFN-gamma synergizes with TNF-alpha or lipopolysaccharide to induce
      robust increases in calcium-independent NO synthase activity. In this study we
      have found that IFN-gamma alone failed to have a significant effect on NO
      synthase activity in BAEC. In contrast to murine macrophages, IFN-gamma inhibited
      TNF-alpha-stimulated induction of endothelial NO synthase activity in a
      concentration-dependent manner. This observation suggests that there is major
      difference in the response of BAEC and murine macrophages to IFN-gamma. A second
      major aim of this study was to determine the effect of IFN-gamma on preproET-1
      mRNA expression and ET-1 secretion rates in BAEC. IFN-gamma alone had little or
      no effect on ET-1 mRNA levels and basal ET release when measured for 8 h.
      However, cotreatment with IFN-gamma potentiated the stimulatory effect of TNF
      alpha on BAEC ET-1 mRNA transcript levels and ET release. In contrast,
      pretreatment of cells with IFN-gamma for 16-24 h blunted the stimulatory effect
      of TNF-alpha. These findings suggest that endothelial cell expression of
      vasoactive mediators is modified by the temporal interplay of at least two immune
      mediators, IFN-gamma and TNF-alpha.

PMID- 1381727
TI  - Proportion of glutamate- and aspartate-immunoreactive neurons in the efferent
      pathways of the rat visual cortex varies according to the target.
AB  - Immunohistochemistry, with antisera directed against glutamate (Glu) or aspartate
      (Asp), was combined with wheat germ agglutinin-horseradish peroxidase (WGA-HRP)
      histochemistry to examine the distribution, morphology, and proportions of Glu-
      and Asp-containing neurons that give rise to corticofugal and callosal
      projections of the rat visual cortex. WGA-HRP injections in the dorsal lateral
      geniculate nucleus resulted in retrograde labelling of small and medium-sized
      cells throughout layer VI of the visual cortex. Of these cells, 60% were also Glu
      immunoreactive and 61% Asp-positive. WGA-HRP injections in the superior
      colliculus labelled large and medium-sized neurons in the upper portion of layer
      V of the visual cortex. Of these cells, 46% were also stained for Glu and 66% for
      Asp. Injections in the pontine nuclei resulted in retrograde labelling of cells
      in the deeper part of cortical layer V. Retrogradely labelled cells, which were
      also immunoreactive for Glu or Asp, were large pyramidal cells. Corticopontine
      neurons, which were also Glu-positive, accounted for 42% of the total number of
      WGA-HRP labelled cells, whilst for Asp-positive neurons this percentage was 51%.
      Finally, after injections in the visual cortex, retrogradely labelled small and
      medium-sized cells were found throughout layers II-VI in the contralateral visual
      cortex. Of these neurons, 38% were also labelled for Glu while 49% were also Asp
      immunoreactive. The present results demonstrate that substantial proportions of
      projection neurons in the rat visual cortex are immunoreactive for Glu or Asp,
      suggesting that these excitatory amino acids are the major transmitters used by
      the cortical efferent systems examined. Furthermore, the proportions of these
      immunoreactive neurons in the efferent pathways vary according to the target.

PMID- 1381728
TI  - Noradrenergic innervation of the thalamic reticular nucleus: a light and electron
      microscopic immunohistochemical study in rats.
AB  - Fluoro-ruby injections in the rat locus coeruleus result in scattered chain-like
      arrays of varicose anterogradely labeled axons within the thalamic reticular
      nucleus of rats. An abundant meshwork of axons giving rise to en passant boutons
      is detected immunohistochemically within this thalamic nucleus by means of an
      antibody to dopamine-beta-hydroxylase (DBH). The density of DBH-positive axonal
      boutons within the reticular nucleus neuropil is greater than that found in the
      relay nuclei of the dorsal thalamus (with the exception of the anterior group
      nuclei). Single DBH-positive axons appear to contact both proximal and distal
      dendrites and occasionally the somata of reticular nucleus neurons. Labeled axons
      are seen closely juxtaposed not only to the swollen segments of the beaded
      reticular neuron dendrites, but to the constricted segments as well. Electron
      microscopic examination of DBH-positive axon terminals within the reticular
      nucleus neuropil indicates that many of the axonal boutons detected light
      microscopically participate in asymmetric synaptic contacts. The postsynaptic
      densities of these synapses are thicker than those of nearby symmetric synapses,
      but often subtend a shorter length of the postsynaptic membrane than the
      densities associated with other nearby asymmetric synapses. These observations
      indicate that the ascending noradrenergic system, in addition to influencing the
      dorsal thalamus and the cerebral cortex directly, is well situated to influence
      signal transmission through the nuclei of the dorsal thalamus indirectly via a
      moderately dense terminal projection upon the thalamic reticular nucleus.

PMID- 1381726
TI  - Cultured human synovial fibroblasts rapidly metabolize kinins and neuropeptides.
AB  - Kinins and substance P have been implicated in the pathogenesis of inflammatory
      arthritis by virtue of their abilities to induce vasodilation, edema, and pain.
      The relative biological potencies of these peptides in vivo would depend at least
      in part upon their rates of catabolism in the joint. We hypothesized that human
      synovial lining cells may regulate intraarticular levels of kinins and
      neuropeptides via degradation by cell surface-associated peptidases. We exposed
      intact human synovial fibroblasts to kinins and substance P, in the presence or
      absence of specific peptidase inhibitors, and measured the amount of intact
      substrate remaining and degradation product(s) generated over time.
      Aminopeptidase M (AmM; EC 3.4.11.2), neutral endopeptidase-24.11 (NEP-24.11; EC
      3.4.24.11), and dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5) were
      identified on the cell surface of synovial cells. Bradykinin degradation was due
      entirely to NEP-24.11 (1.39 +/- 0.29 nmol/min per well). Lysylbradykinin was also
      degraded by NEP-24.11 (0.80 +/- 0.19 nmol/min per well); however, in the presence
      of phosphoramidon, AmM-mediated conversion to bradykinin (3.74 +/- 0.46 nmol/min
      per well) could be demonstrated. The combined actions of NEP-24.11 (0.93 +/- 0.15
      nmol/min per well) and DAP IV (0.84 +/- 0.18 nmol/min per well) were responsible
      for the degradation of substance P. AmM (2.44 +/- 0.33 nmol/min per well) and NEP
      24.11 (1.30 +/- 0.45 nmol/min per well) were responsible for the degradation of
      the opioid peptide, [Leu5]enkephalin. The identity of each of the three
      peptidases was confirmed via synthetic substrate hydrolysis, inhibition profile,
      and immunological identification. The profiles of peptidase enzymes identified in
      cells derived from rheumatoid and osteoarthritic joints were identical. These
      data demonstrate the human synovial fibroblast to be a rich source of three
      specific peptidases and suggest that it may play a prominent role in regulating
      peptide levels in the joint.

PMID- 1381730
TI  - Cytoarchitectonic heterogeneities in the thalamic reticular nucleus of cats and
      ferrets.
AB  - The thalamic reticular nucleus has been classically defined as a group of cells
      surrounding most of the rostral and lateral surfaces of the dorsal thalamus,
      lateral to the fibres of the external medullary lamina and medial to those of the
      internal capsule. With the use of Nissl staining and antibodies to gamma
      aminobutyric acid (GABA), somatostatin, and parvalbumin, this study describes the
      cytoarchitecture of the thalamic reticular nucleus of cats and ferrets. In cats,
      three subdivisions of the nucleus are distinguished, two of which are distinct in
      ferrets also. First, the main body of the reticular nucleus lies lateral to the
      fibres of the external medullary lamina (except ventrally) and medial to those of
      the internal capsule. In both cats and ferrets, this structure is heterogeneous,
      consisting of distinct layers, the details of which vary along the dorsoventral
      axis. A prominent rostroventral portion of comparatively small rounded cells is
      also apparent within the main body. Most reticular cells in all areas of the main
      body are labelled with all of the above mentioned antibodies. Second, the inner
      small-celled region is a group of small cells located between the external
      medullary lamina (ventrally) and the medial margin of the ventral regions of the
      main body of the reticular nucleus: the inner small-celled region is clearly
      differentiated in cats only. Previous studies have referred to this area as being
      part of the main body of the reticular nucleus, but we suggest that it may form a
      separate subnucleus. For example, the inner small-celled region stands in
      striking contrast to the main body of the reticular nucleus in that none of its
      cells are GABA immunoreactive and only a small caudal subpopulation are
      parvalbumin immunoreactive. A very similar pattern of immunostaining is apparent
      for the cells in the zona incerta, although the latter contains a small rostral
      subpopulation of GABA immunoreactive cells. Furthermore, although morphologically
      distinct from the zona incerta, the inner small-celled region fuses with it
      ventrocaudally. We suggest that the inner small-celled region may constitute a
      previously undescribed dorsal extension of the zona incerta, rather than a
      subdivision of the reticular nucleus. Third, the perireticular nucleus, hitherto
      unidentified, is a discrete group of small cells lateral to the main body of the
      reticular nucleus and medial to the corpus striatum (globus pallidus and caudate
      putamen). It is apparent throughout most of the dorsoventral extent of the main
      body of the reticular nucleus of cats and ferrets.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1381729
TI  - Spatial organization of the auditory nerve according to spontaneous discharge
      rate.
AB  - Auditory-nerve fibers in mammals have been classified into three functional
      subclasses according to spontaneous discharge rate (SR). In cat, the peripheral
      terminals of these SR groups are segregated around the sensory cell circumference
      (Liberman, '82, Science 216:1239-1241). The present study shows that this spatial
      segregation is at least partly maintained through the peripheral axonal course
      from sensory cell to spiral ganglion. Analysis of intracellularly labeled
      auditory-nerve fibers shows that peripheral axons and cell bodies of low- and
      medium-SR fibers tend to be found closer to scala vestibuli than high-SR fibers.
      Since low- and medium-SR fibers tend to be thinner, this SR-based segregation can
      also be demonstrated as a fiber-caliber gradient in the osseous spiral lamina.
      The issue of SR-based spatial segregation is relevant to reports that ganglion
      cells near scala vestibuli project to different regions of the cochlear nucleus
      than cells near scala tympani (Leake and Snyder, '89, J. Comp. Neurol. 281:612
      629). Combining the results of the two studies suggests that there may be some SR
      based spatial segregation of inputs to the cochlear nucleus.

PMID- 1381731
TI  - Paucity of glutaminase-immunoreactive nonpyramidal neurons in the rat cerebral
      cortex.
AB  - Glutaminase has been considered to be a synthesizing enzyme of transmitter
      glutamate in pyramidal neurons of the cerebral cortex. In the present study, an
      attempt was made to examine with a double immunofluorescence method whether or
      not nonpyramidal neurons of the cerebral cortex are immunoreactive for
      glutaminase. Glutaminase was stained with mouse anti-glutaminase IgM and FITC
      labeled anti-[mouse IgM] antibody. In the same section, parvalbumin (PA),
      calbindin (CB), choline acetyltransferase (CAT), vasoactive intestinal
      polypeptide (VIP), corticotropin releasing factor (CRF), cholecystokinin (CCK),
      somatostatin (SS), or neuropeptide Y (NPY) was visualized as a marker for
      nonpyramidal neurons with an antibody to each substance, biotinylated secondary
      antibody and Texas Red-labeled avidin. Virtually no glutaminase immunoreactivity
      was seen in PA-, CB-, CAT-, VIP-, CRF-, CCK-, SS-, or NPY-immunoreactive neuronal
      perikarya in the neocortex and mesocortex (cingulate and retrosplenial cortices),
      although it was detected in a few PA-, CB-, VIP-, CCK-, SS-, or NPY
      immunoreactive nonpyramidal neurons in the piriform, entorhinal, and hippocampal
      cortices. PA- and CB-positive neurons have been reported to constitute the major
      population of GABAergic neurons in the cerebral cortex. Thus, the present
      results, together with the previous reports, suggest that most GABAergic,
      cholinergic and peptidergic nonpyramidal neurons in the neo- and mesocortex do
      not contain glutaminase.

PMID- 1381732
TI  - Identification and analysis of the gap region in the 23S ribosomal RNA from
      Actinobacillus actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans is a Gram-negative coccobacillus which can
      cause certain severe extra-oral infections as well as forms of human periodontal
      disease such as localized juvenile periodontitis. In contrast to many prokaryotic
      and eukaryotic species which exhibit an intact 23S ribosomal RNA (rRNA) molecule,
      examination of six A. actinomycetemcomitans strains--including three serogroup
      representative strains and two strains from non-human primates--revealed that
      this micro-organism does not produce an intact 23S ribosomal RNA (rRNA) molecule
      but, rather, two smaller forms of 1.8 kb and 1.2 kb designated as 23S alpha and
      23S beta fragments. On the other hand, 14 other strains of Actinobacillus,
      Haemophilus, and Pasteurella species demonstrated intact 23S rRNA. The sequence
      of the region of the 23S rRNA gene in A. actinomycetemcomitans strain ATCC 43718
      containing the cleavage site was determined by dideoxynucleotide sequencing,
      while the location of the 3' and 5' termini of the 23S alpha and 23S beta
      fragments was resolved by S1 nuclease mapping and cDNA primer-extension. A
      deletion of 112 bases was noted in comparisons of base sequences from A.
      actinomycetemcomitans rRNA and rDNA. The DNA intervening sequence was localized
      to nucleotide 1180 of the Escherichia coli 23S rRNA map. While the primary
      structure of the gap region showed little homology with the gap regions described
      in other organisms, the secondary structure was similar to that previously
      described in the parasitic helminth Schistosoma japonicum. Restriction enzyme and
      nucleotide sequence analysis of the gap region in eight other A.
      actinomycetemcomitans strains showed it to be highly conserved.

PMID- 1381733
TI  - Adsorption of human salivary proteins to hydroxyapatite: a comparison between
      whole saliva and glandular salivary secretions.
AB  - The protein compositions of in vitro pellicles formed from whole saliva and
      parotid and submandibular secretions were determined by use of synthetic
      hydroxyapatite as a model for dental enamel. The adsorbed and unadsorbed protein
      fractions were analyzed by amino acid analysis and both anionic and cationic
      discontinuous polyacrylamide gel electrophoresis. For further characterization of
      the in vitro pellicle, the adsorbed fractions were subjected to gel filtration on
      Sephadex G-100 and reversed-phase chromatography on C18 columns. Amylase, acidic
      and glycosylated proline-rich proteins, statherins, and histatins were identified
      in the parotid-derived pellicle. Detailed analysis of the statherin-containing
      fractions resulted in the observation of several statherin-like proteins. The use
      of cationic gel electrophoresis allowed for the identification of histatin 3 and
      histatin 5, which have not been previously detected in pellicle formed in vitro.
      The protein composition of submandibular-derived pellicle was similar to that of
      parotid-derived pellicle except for the presence of cystatins and the absence of
      glycosylated proline-rich proteins. In contrast, in vitro pellicle derived from
      whole saliva exhibited a vastly different composition, consisting primarily of
      amylase, acidic proline-rich proteins, cystatins, and proteolytically-derived
      peptides. The results indicate that acidic phosphoproteins as well as neutral and
      basic histatins from pure secretions selectively adsorb to hydroxyapatite,
      whereas in whole saliva some of these proteins are proteolytically degraded,
      dramatically changing its adsorption pattern.

PMID- 1381734
TI  - Evaluation of subsurface defects created during the finishing of composites.
AB  - The objective of this study was to test the hypothesis that a degraded subsurface
      layer containing microcracks is produced in dental composites as a result of
      finishing procedures. Various composites in the form of rectangular bars were
      finished with a 12-fluted carbide bur or a fine diamond within minutes of light
      curing, and were subsequently stained with silver nitrate. Microscopic evaluation
      revealed that significant penetration of stain occurred in the unfinished as well
      as in the finished surfaces. The extent of dye penetration that could be directly
      attributed to a damaged layer produced by the finishing procedure was less than
      10 microns, being greatest for a microfill (Silux Plus) and a hybrid (P-50)
      composite. There was no difference between the effects of the finishing
      instruments. SEM analysis of the subsurface showed an absence of any cracks for
      the composites. However, occasional disruption of the interface between the pre
      polymerized resin fillers and the matrix was apparent for the microfill material.
      The results showed that only a very limited subsurface damage may be created in
      certain composites during the initial contouring of a restoration.

PMID- 1381735
TI  - Hepatitis C virus RNA and hepatitis C virus antibody in the serum of patients
      with abnormal liver function.
AB  - In order to elucidate the relation between hepatitis C virus (HCV) RNA and
      antibody to HCV (anti-HCV) in serum, we examined samples of serum collected from
      228 HBsAg-negative patients, with abnormal alanine aminotransferase (ALT) values,
      for HCV-RNA by nested polymerase chain reaction (PCR) assay and for anti-HCV
      using C100 protein as the antigen. HCV-RNA was detected in 99 (92.5%) of 107 anti
      HCV-IgG-positive samples, regardless of ELISA optical density cut-off value
      (ELISA ratio), and in 34 (28.1%) of 121 anti-HCV-IgG-negative samples in which
      the frequency of the presence of HCV-RNA became higher in proportion to the ELISA
      ratio. Among 42 discordant cases (34 anti-HCV-IgG-negative, RNA-positive cases
      and eight anti-HCV-IgG-positive, RNA-negative cases), 10 were positive for anti
      HCV-IgM (8/34 and 2/8, respectively) irrespective of clinical status. These
      findings suggest that in patients with abnormal ALT values, even if they are anti
      HCV-IgG negative, HCV infection cannot be excluded. Furthermore, PCR assay for
      detecting HCV-RNA may be more suitable for identifying patients with infectious
      virus than is detection of anti-HCV-IgG. Detection of anti-HCV-IgM may also be
      useful.

PMID- 1381736
TI  - [Tau protein kinase].

PMID- 1381737
TI  - [Cyclophilin and FK506-binding protein].

PMID- 1381738
TI  - Role of nitric oxide signal transduction pathway in regulation of vascular tone.
AB  - Nitric oxide signal transduction pathway has been detected in a number of cell
      types including vascular endothelial cells, smooth muscle cells, and
      noncholinergic nonadrenergic nerve endings. Nitric oxide synthase is a key enzyme
      which produces nitric oxide from L-arginine. Three different types of this enzyme
      have been described: constitutive soluble, inducible soluble, and constitutive
      particulate. Nitric oxide is a lipophilic molecule that can rapidly diffuse
      through biological membranes. It provides communication between endothelial and
      smooth muscle cells as well as between nerve endings and smooth muscle cells.
      Decreased production of nitric oxide may lead to vasospasm, whereas its
      overproduction may cause pathological vasodilatation. Understanding of the role
      of nitric oxide signal transduction pathway in regulation of vascular tone will
      facilitate design of better strategies for the prevention and treatment of
      vascular diseases.

PMID- 1381739
TI  - Antibody responses to the 18-kDa protein of Mycobacterium leprae in leprosy and
      tuberculosis patients.
AB  - The 18-kDa protein of Mycobacterium leprae, as recognized by the monoclonal
      antibody L5, has a restricted species distribution, being confined to M. leprae
      and M. habana. We have developed a solid-phase ELISA using purified, recombinant
      M. leprae 18-kDa protein and compared the serological responses of Nepali leprosy
      and tuberculosis patients and endemic control subjects to the protein and the M.
      leprae phenolic glycolipid-I (PGL-I). Few control subjects had anti-18-kDa
      antibodies. A small proportion of paucibacillary (PB) leprosy and 42% of
      multibacillary (MB) leprosy patients had IgG anti-M. leprae antibodies. A similar
      proportion (47%) of Nepali tuberculosis (TB) patients were seropositive, and IgG
      anti-18-kDa antibody levels were significantly higher in MB and TB patients than
      in control subjects. By comparison, IgM anti-PGL-I antibodies were detected in
      88% of MB leprosy patients and only 7% of TB patients. The possible reasons for
      the 18-kDa protein seroreactivity in TB patients are discussed, and the anti-18
      kDa assay is compared with other antibody assays for protein and nonprotein
      antigens of M. leprae. It is concluded that the sensitivity and specificity of
      the anti-M. leprae 18-kDa ELISA are insufficient for the assay to be of clinical
      utility in leprosy patients.

PMID- 1381740
TI  - Polymerase chain reaction amplifying DNA coding for species-specific rRNA of
      Mycobacterium leprae.
AB  - The sensitivity of the polymerase chain reaction (PCR) on the DNA coding for the
      species-specific fragment of 16S rRNA of Mycobacterium leprae studied on mouse
      foot pad harvests and human skin biopsies varies widely between 1 and 3 x 10(4)
      organisms. This is probably the result of variations in the proportions of
      organisms with sufficiently intact DNA suitable for PCR. Preserving human skin
      biopsies for 3 weeks at an ambient temperature even after boiling for 6 minutes
      gives rise to a 10-fold decrease in sensitivity. Fixation of tissues in formol
      10% or Lowy fixative or preserving in Dubos OAA broth is very harmful to the PCR,
      mainly due to the enhancement of an inhibitory effect on the PCR reaction. For
      preservation, the best choice at the moment seems to be alcohol 70%. Sample
      preparation of five cycles of freeze-boiling is simple and generally more
      efficient than proteinase K treatment and DNA extraction.

PMID- 1381741
TI  - [Sensitizing capacity, cross-reactivity and antigenic determinants of bisphenol
      A].
AB  - Bis-GMA and epoxy resins are known to cause allergic reactions in some patients.
      The purpose of this research was to investigate the sensitizing capacity, cross
      reactivity and antigenic determinants of bisphenol A (BPA), a major constituent
      of Bis-GMA and BPA type epoxy resins. Anti-BPA antibodies were prepared from mice
      injected with BPA-ovalbumin conjugates (BPA-OVA), and the reactions of the
      structurally BPA-related compounds were compared with that of BPA using these
      antibodies by the enzyme immunoassay (EIA) and EIA inhibition test. The findings
      are as follows: 1) Injection of BPA failed to generate anti-BPA antibodies.
      However, injection of BPA-OVA was effective in producing antibodies strongly
      reacting with BPA. 2) Polyclonal anti-BPA antibodies cross-reacted with bisphenol
      B (BPB), p-isopropyl-phenol (IPP), diethylstilbestrol (DES) and 2,4-dinitrophenyl
      (DNP). 3) Five kinds of monoclonal anti-BPA antibodies were obtained. These
      monoclonal antibodies reacted specifically with BPA and moderately cross-reacted
      with IPP, DES and BPB, but not with DNP. The results suggest that BPA-OVA is
      capable of eliciting anti-BPA antibody production in mice and that the antigenic
      determinant of BPA is the structure of one central carbon atom, covalently bound
      with two phenyl groups and two methyl groups.

PMID- 1381742
TI  - Relationship of large and small CD3- CD56+ lymphocytes mediating NK-associated
      activities.
AB  - We have defined a population of CD3-, CD56+ small lymphocytes (SLs) that exhibit
      the same phenotype and lytic capacity as natural killer (NK) cells. NK cells
      characteristically express the surface markers CD16 and CD56, mediate non-major
      histocompatibility complex (MHC)-restricted lysis, and have been equated with CD3
      large granular lymphocytes (LGLs). In the present study we extended the
      observation that CD3-, CD56+ SLs can mediate NK- and antibody-dependent cellular
      cytotoxicity activity by studying the activation signals and lytic mechanisms
      that might be utilized by CD3-, CD56+ SLs in comparison to CD3- CD56+ LGLs. Our
      results show that CD3- SLs, similar to CD3- LGLs, exhibited activated killing in
      response to interleukin-2 (IL-2). In addition, after IL-2 activation, the CD3-
      SLs exhibited morphologic changes, including increases in size and granularity,
      and both morphologically and phenotypically became virtually indistinguishable
      from CD3- LGLs. Similar to CD3- LGLs, CD3- SLs could be directly activated by IL
      2 alone to secrete significant quantities of interferon-gamma (IFN-gamma) and to
      express IL-2 receptor (IL-2R) p55. Examination of serine esterases and pore
      forming protein (PFP) demonstrated that these cells exhibited a cytoplasmic
      distribution of perforin, which, unlike that of CD3- LGLs, was not associated
      with dense cytoplasmic azurophilic granules. Serine esterase levels were similar.
      However, after IL-2 activation PFP was concentrated in dense cytoplasmic
      granules, similar or identical to the situation in CD3-, CD56+ LGLs. These CD3-,
      CD56+ subsets appear to represent a continuum of activated cells that might
      represent various states of maturation of NK cells.

PMID- 1381743
TI  - Low response of BALB/c macrophages to priming and activating signals.
AB  - Trehalose dimycolate (TDM), a mycobacterial glycolipid, is a powerful macrophage
      priming agent. However, its efficiency seems limited in the case of BALB/c mice.
      Peritoneal macrophages harvested from TDM-treated BALB/c mice did not control BCG
      growth in vitro as efficiently as similar macrophages from two other mouse
      strains, (B6 x D2)F1 and C57BL/6, which are respectively Bcgr and Bcgs. BALB/c
      macrophages elicited by TDM also exhibited a low capacity to produce hydrogen
      peroxide and, after activation by lipopolysaccharide (LPS), weak cytostatic
      activity against P815 mastocytoma cells. Finally, alkaline phosphodiesterase, a
      marker of resident and inflammatory macrophages, was still expressed at a high
      level in macrophages of BALB/c mice treated with TDM. Low responsiveness of
      BALB/c macrophages to stimuli was not observed with TDM only; activation for
      tumor cytotoxicity of thioglycolate-elicited macrophages from BALB/c mice
      required also higher doses of interferon-gamma, and LPS. L-Arginine-dependent
      production of nitric oxide was inducible in macrophages from BALB/c mice, but the
      conditions required for its induction were more stringent. Thus, the reduced
      antiproliferative effects of BALB/c macrophages may be due to uncomplete
      induction of NO synthase after suboptimal stimulation.

PMID- 1381744
TI  - Interferon-gamma and interleukin-4 down-regulate soluble CD14 release in human
      monocytes and macrophages.
AB  - CD14 is a 53-kd glycoprotein that is mainly expressed in myeloid cells and exists
      in two forms. The membrane-bound form represents the receptor for complexes of
      lipopolysaccharide (LPS) with LPS binding protein. The function and regulation of
      the soluble form are unknown. In the present study we investigated the release of
      soluble CD14 (sCD14) in cultures of human mononuclear leukocytes, elutriated
      monocytes, and monocyte-derived macrophages. The release of sCD14 into the medium
      of the cells cultured for 15 and 45 h was investigated in the absence or presence
      of selected cytokines. sCD14 release occurred constitutively and correlated with
      cell number. In monocytes differentiating into macrophages, cumulative release of
      sCD14 was linear from day 1 to day 7. Spontaneous sCD14 release after 15 h of
      culture (2 x 10(6) cells/ml) was higher in the supernatant from monocytes (314 +/
      58 ng/ml) than that from mononuclear leukocytes (68 +/- 10 ng/ml) and similar to
      that from macrophages (469 +/- 79 ng/ml). Cycloheximide and actinomycin D
      inhibited sCD14 release. Recombinant interferon-gamma (rIFN-gamma) and
      recombinant interleukin-4 (rIL-4) directly decreased sCD14 release in mononuclear
      leukocyte, monocyte, and macrophage cultures. rIL-2 and rIFN-alpha reduced sCD14
      release into the supernatants of mononuclear leukocytes only. Use of anti-IFN
      gamma antibodies indicated that the down-regulation of sCD14 release by rIL-2 and
      rIFN-alpha was partially due to induction of endogenous IFN-gamma. The down
      regulation of sCD14 release by all four cytokines was both time and dose
      dependent. rIFN-gamma and rIL-4 added simultaneously had a synergistic effect on
      sCD14 down-regulation. In conclusion, sCD14 release may have an immunomodulatory
      role in circulating monocytes, is apparently not related to the process of
      macrophage differentiation, and is selectively down-regulated during an immune
      response when levels of IFN-gamma and IL-4 are high.

PMID- 1381745
TI  - An empirical evaluation of three components of the tetrahedron model of clinical
      judgment.
AB  - The tetrahedron model of clinical judgment (Rock, Bransford, Maisto, and Morey,
      Clin. Psychol. Rev. 7:645-661, 1987; Rock, Bransford, Morey, and Maisto, Clin.
      Psychol. Rev. 8:411-416, 1988) provides a framework for identifying factors that
      may influence the judgments of psychotherapists (e.g., clinical and counseling
      psychologists, psychiatrists, social workers, etc). Three parameters of the model
      were experimentally manipulated: mode of of presentation of clinical information,
      patient, and judgment task. Sixteen clinical psychology graduate student
      therapists evaluated two patients on axis I and axis II of the DSM-III.
      Judgmental accuracy was influenced by main effects and two- and three-way
      disordinal interactions among the three model parameters. Additionally, we found
      that judgemental accuracy was positively related to experience and training. This
      relationship was evident only when experience was assessed with specific rather
      than general measures, and when the clinical materials were presented in an
      audiovideo format and hence resembled the conditions under which the clinicians
      in the study acquired that training and experience. Implications for the design
      of training programs that facilitate competency in clinical judgment are
      discussed.

PMID- 1381746
TI  - Injection of bleomycin as a primary therapy of cystic lymphangioma.
AB  - Forty-five patients (19 boys and 26 girls) with lymphangioma have been treated at
      Osaka University Hospital during the 10-year period from January 1978 to December
      1987. Twenty-nine underwent initial bleomycin (BLM) therapy. These patients'
      lesions consisted of large cystic masses that were demonstrated by echography or
      computed tomography scans. BLM was administered as a solution of 1 mg/mL in
      saline, after aspiration of the cyst contents using a puncture needle. The total
      dose ranged from 3 mg to 32 mg (average, 10 mg) and was administered between 1
      and 16 times. Of the 29 cases treated with BLM, 25 cases (86%) showed significant
      reduction of the mass and 16 (55%) showed complete disappearance. Recurrence
      occurred in 3 patients. One responded to further injection of BLM, and the other
      2 required surgical resection. Thirteen patients required surgical resection;
      however, in those cases, the previous injection of BLM was found to minimize the
      extent of surgical resection required. There were no serious side effects with
      BLM injection. Injection of BLM as an initial treatment of cystic lymphangioma
      was found to be very useful. It can reduce the size of the mass and even result
      in complete disappearance; consequently, it can minimize the frequency and extent
      of surgical intervention.

PMID- 1381747
TI  - Uptake of fractionated [3H]heparin by rat parenchymal hepatocytes in primary
      culture: effects of alpha-globulin, temperature, and pH.
AB  - The mechanism of uptake of fractionated [3H]heparin in conjunction with the
      effect of alpha-globulin (the major binding protein of heparin) was investigated
      in primary cultures of rat parenchymal hepatocytes. The uptake clearances were
      estimated from the initial linear phase, up to 1 min, of the uptake-versus-time
      profile. The uptake clearance for fractionated [3H]heparin was 11.0 mL/min/g of
      liver at 7.5 nM fractionated [3H]heparin in the absence of alpha-globulin. This
      value decreased with increasing concentration of alpha-globulin in the incubation
      solution, a fact suggesting that the rate of uptake of alpha-globulin-bound,
      fractionated [3H]heparin is lower than that of unbound [3H]heparin, as generally
      assumed for hepatic drug elimination. However, the uptake clearance in the
      presence of alpha-globulin at 8 mg/mL, where free, fractionated [3H]heparin was
      supposed to be negligible according to the results of our in vitro study, was
      approximately 12% of that in the absence of alpha-globulin. These results suggest
      that alpha-globulin-bound, fractionated [3H]heparin also contributes to the
      uptake of fractionated [3H]heparin. This effect on uptake could be explained by
      the protein-mediated transport concept rather than the traditional assumption
      that protein-bound drugs are not transported. The uptake clearance was reduced
      significantly by reducing the incubation temperature from 37 to 4 degrees C.
      However, neither the pH of the incubation solution (6.4-8.4) nor several
      inhibitors of active transport had any clear effects on the uptake clearance.

PMID- 1381748
TI  - Role of intracellular Ca2+ on histamine release from rat peritoneal mast cells.
AB  - The benzoic acid derivative 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
      hydrochloride (TMB-8) strongly inhibited histamine release from rat peritoneal
      mast cells induced by various secretagogues. TMB-8 also inhibited Ca2+
      mobilization from intracellar Ca2+ stores. However, histamine release induced by
      compound 48/80 (condensation product of N-methyl-p-methoxy-phenethylamine and
      formaldehyde) was not affected by TMB-8. These results indicate that Ca2+
      mobilization is necessary to elicit the release of histamine from mast cells.

PMID- 1381749
TI  - Cationic channels sensitive to extracellular ATP in rat lacrimal cells.
AB  - 1. Responses of isolated rat lacrimal cells to local applications of ATP were
      studied using tight-seal whole-cell recording and/or Fura-2-derived calcium
      concentration measurements. 2. In cells where variations in Ca2+ concentration
      were prevented by use of a strong Ca2+ buffer, ATP was found to induce an inward
      current response at negative holding potentials. With 10 microM-ATP, the current
      amplitude ranged between 20 and 200 pA. The reversal potential of this ATP
      induced current was close to 0 mV with normal external solution and shifted to 
      19 +/- 3 mV (mean +/- S.D.) when the concentration of external monovalent cations
      was halved. These results indicate that the channels have a cationic selectivity.
      The response amplitude decreased markedly from trial to trial, indicating a
      desensitization process which was irreversible on the time scale of the
      recordings. 3. Steady state I-V curves for the ATP-induced current in normal
      saline showed a marked inward rectification. This rectification appeared to be
      linked to a time-dependent activation of the channels, as hyperpolarizing voltage
      jumps elicited a time-dependent current increase. This relaxation could be fitted
      by a double-exponential function, with time constants (at -120 mV) of 0.9 +/- 0.3
      ms and 110 +/- 6.4 ms. 4. Variance analysis of the ATP-induced current gave a
      single-channel current value of 0.34 pA at -60 mV. The single-channel current
      amplitude varied linearly with potential, with a slope close to 6 pS. The
      relation between noise covariance and time could be fitted by a double
      exponential function, with time constants (at -60 mV) of 0.8 +/- 0.4 ms and 6.8
      +/- 3.4 ms (mean +/- S.D.). 5. In an isotonic Ca2+ solution, 10 microM-ATP
      induced an inward current at -60 mV with a calculated single-channel current
      amplitude obtained from noise analysis close to 0.2 pA. In an external solution
      containing 10 mM-calcium and no sodium, 50 microM-ATP elicited a current with a
      reversal potential of -19 mV. 6. Fura-2 measurements were performed in intact
      cells or in cells dialysed with a low concentration of Ca2+ buffer (e.g. 0.5 mM
      EGTA). Under such conditions ATP induced increases of the internal Ca2+
      concentration with very variable amplitudes. In some cells Ca2+ rises of 50 nM or
      lower were found. Minimal activation of Ca(2+)-dependent channels was then
      observed. In other cells large Ca2+ rises (up to 500 nM) were observed and were
      then correlated with marked activation of Ca(2+)-dependent channels.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1381750
TI  - Role of cyclic nucleotides and calcium in the nutrient-induced release of
      cholecystokinin-like immunoreactivity in rats.
AB  - 1. This study was undertaken with an isolated vascularly perfused rat
      duodenojejunal preparation to investigate the mechanisms of the release of
      cholecystokinin measured by immunoassay (cholecystokinin-like immunoreactivity,
      CCK-LI). 2. Intra-arterial infusion of forskolin (2-20 microM) evoked a prompt
      and well-sustained secretion of CCK-LI which was increased to a mean value of
      600% of basal with the highest dose tested. 3-Isobutyl-1-methylxanthine (IBMX)
      (10(-6)-10(-4) M) stimulated the secretion of CCK-LI (maximal increase of 400% of
      basal at 10(-4) M). 3. Intra-arterial infusion of beta-phorbol 12-myristate 13
      acetate (5 x 10(-7)-5 x 10(-6) M) and calcium ionophore A23187 (10(-6)-10(-5) M)
      alone or in combination provoked only a transient increase in the release of CCK
      LI. 4. Luminal infusion of a 5% ovalbumin hydrolysate solution produced an
      immediate release of CCK-LI followed by a well-sustained secretion at 580% of
      basal. Intra-arterial infusion of IBMX (10(-5) or 10(-4) M) in combination with
      luminal peptone induced a release of CCK-LI which was equal to the sum of the CCK
      responses evoked by IBMX and peptone given separately. 5. Intra-arterial infusion
      of EGTA (2 mM) abolished the forskolin- and peptone-induced CCK secretion while
      luminal EGTA (2 mM) had no inhibitory effect. Verapamil (5 x 10(-5)-10(-4) M) or
      nifedipine (10(-5)-5 x 10(-5) M) inhibited the peptone-evoked CCK secretion. A
      high concentration of trifluoperazine (10(-4) M) strongly reduced the release of
      CCK-LI induced by intraluminal peptone while 10(-5) M was ineffective. 6. It is
      concluded that the peptone-induced secretion of CCK-LI involves a cyclic AMP
      dependent mechanism and the activation of calcium channels possibly located at
      the basolateral side of the CCK cell.

PMID- 1381751
TI  - Changes in the electrical properties of chick ciliary ganglion neurones during
      embryonic development.
AB  - 1. Whole-cell recording techniques were used to examine the expression of ionic
      currents in chick ciliary ganglion neurones dissociated acutely at various stages
      of embryonic development. Currents were also examined in dissociated cells that
      had been maintained in vitro for several days. 2. Voltage-activated, tetrodotoxin
      (TTX)-sensitive Na+ currents (INa) could be detected in all cells tested between
      stage 25 and stage 40 (embryonic days 4.5-14). INa increased in both amplitude
      and density throughout development, but no obvious changes in kinetics or
      sensitivity to TTX were observed. 3. High-threshold Ca2+ currents (ICa) were also
      detectable between stage 25 and stage 40. ICa increased in both amplitude and
      density throughout this time. No obvious changes in kinetics or voltage
      dependence were observed. 4. Delayed rectifier K+ currents (IDR) and A-currents
      (IA) could be detected in Ca(2+)-free salines, and distinguished on the basis of
      differences in kinetics, voltage dependence, and sensitivity to
      tetraethylammonium (TEA). IA was either absent, or present at very low densities
      at stages 26-30, but showed a sharp increase in density thereafter. In contrast,
      IDR was detectable as early as stage 25, and did not display a significant
      increase in density during development. 5. Ca(2+)-activated K+ currents (IK(Ca))
      were either undetectable or present at very low density between stage 26 and
      stage 30 (embryonic days 5-9) but showed a large increase in amplitude and
      density thereafter. 6. Ionic currents were examined in age-matched cells
      dissociated acutely on embryonic day 13, or isolated on embryonic day 9 and
      maintained in vitro for an additional 4 days. Most of the cells maintained in
      culture for 4 days did not express detectable IK(Ca), and had significantly
      reduced IA compared to acutely isolated controls. The cultured cells expressed
      normal densities of IDR, ICa and INa. 7. All ionic currents increased in
      amplitude during normal embryonic development, and all but IDR increased in
      density. The largest change in density generally occurred between stages 30 and
      40, during which time ciliary ganglion neurones form synapses with target
      tissues. 8. Isolation of ciliary neurones from the in ovo environment prevented
      the normal development of IA and IK(Ca), suggesting that the expression of these
      channels is controlled by one or more extrinsic environmental factors. In
      contrast, the normal expression of INa, ICa and IDR is not dependent upon
      extrinsic factors.

PMID- 1381752
TI  - Direct modulation of GABAA receptor by intracellular ATP in dissociated nucleus
      tractus solitarii neurones of rat.
AB  - 1. Effect of intracellular ATP on Cl- current (ICl) mediated by the GABA (gamma
      aminobutyric acid) receptor subtype, GABAA, was studied in dissociated nucleus
      tractus solitarii (NTS) neurones using the whole-cell mode of patch clamp. A
      concentration-jump technique termed 'Y tube' was used to rapidly apply agents
      externally. Dissociated neurones were obtained from 1- to 3-week-old rats. 2.
      When the patch-pipette solution contained 2 mM-ATP, the amplitude of ICl elicited
      by 10(-5) M-GABA did not show any time-dependent decrease (apparent run-down),
      for more than 60 min after the initial recording. In the presence of ATP, the
      half-maximum concentration (KD) and Hill coefficient calculated from the GABA
      concentration-response curve were 9.12 microM and 1.47, respectively. 3. In the
      absence of intracellular ATP, the amplitude of GABA-induced ICl decreased with
      time. The relative peak amplitudes after 20 and 60 min from the initial recording
      were 0.40 +/- 0.09 (n = 11) and 0.16 +/- 0.05 (n = 8) with respect to the initial
      response. 4. Removal of Mg2+ from the internal solution induced run-down of the
      GABA response even in the presence of 2 mM-intracellular ATP, suggesting that
      both intracellular ATP (2 mM or more) and Mg2+ are necessary to prevent run-down
      of the GABA response. 5. Activation of dephosphorylation processes by alkaline
      phosphatase (100-200 microM) did not affect the GABA response in neurones
      perfused with internal solution containing 2 mM-ATP and 3 mM-Mg2+. Blocking the
      dephosphorylation process by okadaic acid, a phosphatase inhibitor, did not
      prevent the run-down of the GABA response. 6. Calcium influxes passing through
      both the voltage-dependent L-type Ca2+ channel and the glutamate receptor
      operated cation channel did not affect ICl induced by GABA. 7. GABA-induced ICl
      was also maintained by adding 2 mM-ADP or ATP gamma S (adenosine-5'-O-3
      thiotriphosphate) to the internal solution containing Mg2+. Addition of 2 mM
      adenosine, AMP, cyclic AMP, AMP-PNP (adenylimido-diphosphate) or ADP beta S
      (adenosine-5'-O-2-thiodiphosphate) to the internal solution did not prevent the
      run-down of the GABA response even in the presence of 3 mM-intracellular Mg2+.
      Based on the chemical specificity of these ATP analogues, it is suggested that
      there is an ATP-sensitive binding site (ATP receptor) in the cytoplasmic side of
      the cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1381754
TI  - Cation interactions within the cyclic GMP-activated channel of retinal rods from
      the tiger salamander.
AB  - 1. The ionic dependence of current through the 3',5'-cyclic guanosine
      monophosphate (cyclic GMP)-activated channels of salamander rods was studied in
      excised inside-out membrane patches from isolated outer segments. Voltage-clamp
      experiments on transducing rods were performed so that the channels in intact
      cells could be compared with those in excised patches. 2. The reversal potential
      of the cyclic GMP-induced patch current was close to the Na+ equilibrium
      potential when the concentration of NaCl on the cytoplasmic surface of a patch
      was varied at constant external NaCl concentration. Fitting the Goldman-Hodgkin
      Katz equation indicated that the apparent ratio of permeabilities for Na+ and Cl-
      was at least 50. This confirms a previous report that the channel's Na+
      permeability is much larger than its Cl- permeability. 3. Na+ currents through
      the channel did not obey the independence principle. The outward patch current at
      large positive potential began to saturate with increasing concentrations of
      internal Na+, as if permeation required Na+ to bind to a site with an apparent
      dissociation constant around 180 mM. 4. In symmetrical NaCl solutions containing
      very low concentrations of divalent cations the current-voltage relation measured
      from excised patches 50 microseconds after switching the voltage showed mild
      outward rectification. By 1 ms the rectification was more pronounced. The
      rectification at 50 microseconds is attributed to voltage dependence of Na+
      permeation. The additional rectification at later times is attributed to voltage
      dependence of the channel's probability of being open, depolarization favouring
      the open state. 5. In symmetrical Mg2+ solutions the cyclic GMP-induced patch
      currents were smaller and the outward rectification was more pronounced. 6.
      Addition of Mg2+ or Ca2+ to an internal Na+ solution blocked the cyclic GMP
      induced Na+ current through the channels, as if by occupying a single binding
      site with an affinity in the 0.1-2 mM range. Block by Mg2+ was voltage dependent,
      suggesting that the binding site was within the channel's transmembrane electric
      field. Raising the Mg2+ concentration on the external surface of the patch
      increased the apparent dissociation constant of block by internal Mg2+, as
      expected if external and internal Mg2+ compete for the same binding site. 7.
      Block by internal Ca2+ had an opposite and weaker voltage dependence than block
      by internal Mg2+. 8. In symmetrical solutions containing both Na+ and Mg2+ the
      outward rectification was more pronounced than in solutions containing Na+ alone.
      In solutions thought to be close to physiological the outward patch current
      increased e-fold for a depolarization of 24-30 mV.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1381755
TI  - Loss of epithelial L1 expression is associated with cellular invasion of oral
      squamous cell carcinomas.
AB  - Recent studies have suggested that the epithelial expression of two leukocyte
      related proteins, human class II HLA-DR antigen and myelomonocytic L1 antigen,
      depends on a certain state of cellular maturation and differentiation. We have
      studied HLA-DR and L1 expression in oral squamous cell carcinomas. The epithelial
      distribution of these proteins was evaluated in relation to differentiation
      alterations by two-color immunofluorescence staining with cytokeratins (K14 and
      K13) as a baseline. HLA-DR was infrequently expressed in oral carcinomas,
      apparently being unrelated to the degree of differentiation and the subepithelial
      leukocyte infiltration. L1 was generally present in oral epithelium but
      disappeared in the most invasive cells of carcinomas. These cells were also K14
      and K13 negative suggesting an abnormal state of differentiation. L1 has been
      suggested to have an inhibitory effect on casein kinases I and II, enzymes
      possibly associated with cell proliferation; it might therefore exert an
      inhibitory effect on tumor growth. Its absence could be an interesting aspect of
      the invasiveness of oral carcinoma cells.

PMID- 1381753
TI  - Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate
      receptors in Xenopus oocytes.
AB  - 1. N-Methyl-D-aspartate (NMDA) receptors were expressed in Xenopus oocytes
      injected with rat brain RNA. The modulation of NMDA-induced currents was examined
      by activating protein kinase C (PKC) either directly (using phorbol esters) or
      indirectly (via metabotropic glutamate agonists). 2. Bath application of the PKC
      activator, 4-beta-phorbol-12,13-dibutyrate (PDBu) resulted in a two-fold increase
      in the NMDA-evoked current at all holding potentials examined (-80 to 0 mV). The
      inactive (alpha) stereoisomer of phorbol ester was ineffective. 3. The increase
      was observed under conditions that eliminate the oocyte's endogenous calcium
      dependent chloride current, which often contributes to the NMDA response in
      oocytes. 4. The PDBu effect was specific to the NMDA subclass of glutamate
      receptors in that no increase was observed in the responses to two other
      glutamate agonists, kainate and AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid). 5. Stimulation of PKC by activation of metabotropic receptors
      via either quisqualate or trans-ACPD (trans-1-aminocyclopentane-1,3-dicarboxylic
      acid) also led to an increase in NMDA currents. 6. Both methods of enhancement
      induced transient effects. PDBu effects lasted 10-45 min, depending upon both
      dose and length of application. Quisqualate and trans-ACPD effects were shorter,
      lasting less than 10 min under these conditions of application. 7. Both methods
      of enhancement were blocked by the PKC inhibitor, staurosporine. In addition, the
      phorbol ester-induced enhancement of NMDA responses occluded further enhancement
      by quisqualate. 8. The results suggest a role for metabotropic glutamate
      receptors in modulation of NMDA-mediated processes.

PMID- 1381756
TI  - Inhibition of fertilization by a monoclonal antibody recognizing the
      oligosaccharide sequence GalNAc beta 1----4Gal beta 1----4 on the mouse zona
      pellucida.
AB  - Mouse eggs and pre-implantation stage embryos express on their surfaces a
      carbohydrate epitope, TEC-2, defined by an IgM monoclonal antibody, TEC-02. The
      TEC-2 epitope involves the oligosaccharide sequence GalNAc beta 1----4Gal beta 1-
      --4 that is expressed on the plasma membrane and zona pellucida of mouse eggs and
      on a very limited number of other cell types. In this study we addressed the
      question whether or not the binding of TEC-02 antibody to the mouse eggs would
      interfere with their fertilization. Our data showed that the TEC-2 epitope is
      carried by two zona pellucida glycoproteins, ZP2 and ZP3. Binding of TEC-02
      antibody to mouse eggs inhibited specifically and in a dose-dependent manner
      their fertilization in vitro. The inhibitory effect of TEC-02 antibody was
      dependent on the presence of an intact zona pellucida. Direct radioantibody
      binding assays indicated that the TEC-02 antibody completely inhibited
      fertilization at a concentration at which one quarter of all available TEC-2
      binding sites was occupied. Binding of TEC-02 antibody to an egg did not
      interfere with initial attachment of the sperm to the egg but inhibited
      maintenance of sperm binding to the zona pellucida, the secondary binding. The
      combined data indicate that TEC-2, which is a well-defined zona pellucida
      specific carbohydrate epitope, might be a part of the secondary sperm receptor.

PMID- 1381757
TI  - Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab
      complex.
AB  - The crystal structure of the complex between neuraminidase from influenza virus
      (subtype N9 and isolated from an avian source) and the antigen-binding fragment
      (Fab) of monoclonal antibody NC41 has been refined by both least-squares and
      simulated annealing methods to an R-factor of 0.191 using 31,846 diffraction data
      in the resolution range 8.0 to 2.5 A. The resulting model has a root-mean-square
      deviation from ideal bond-length of 0.016 A. One fourth of the tetrameric complex
      comprises the crystallographic model, which has 6577 non-hydrogen atoms and
      consists of 389 protein residues and eight carbohydrate residues in the
      neuraminidase, 214 residues in the Fab light chain, and 221 residues in the heavy
      chain. One putative Ca ion buried in the neuraminidase, and 73 water molecules,
      are also included. A remarkable shape complementarity exists between the
      interacting surfaces of the antigen and the antibody, although the packing
      density of atoms at the interface is somewhat looser than in the interior of a
      protein. Similarly, there is a high degree of chemical complementarity between
      the antigen and antibody, mediated by one buried salt-link, two solvated salt
      links and 12 hydrogen bonds. The antibody-binding site on neuraminidase is
      discontinuous and comprises five chain segments and 19 residues in contact,
      whilst 33 neuraminidase residues in eight segments have 899 A2 of surface area
      buried by the interaction (to a 1.7 A probe), including two hexose units.
      Seventeen residues in NC41 Fab lying in five of the six complementarity
      determining regions (CDRs) make contact with the neuraminidase and 36 antibody
      residues in seven segments have 916 A2 of buried surface area. The interface is
      more extensive than those of the three lysozyme-Fab complexes whose crystal
      structures have been determined, as judged by buried surface area and numbers of
      contact residues. There are only small differences (less than 1.5 A) between the
      complexed and uncomplexed neuraminidase structures and, at this resolution and
      accuracy, those differences are not unequivocal. The main-chain conformations of
      five of the CDRs follow the predicted canonical structures. The interface between
      the variable domains of the light and heavy chains is not as extensive as in
      other Fabs, due to less CDR-CDR interaction in NC41. The first CDR on the NC41
      Fab light chain is positioned so that it could sterically hinder the approach of
      small as well as large substrates to the neuraminidase active-site pocket,
      suggesting a possible mechanism for the observed inhibition of enzyme activity by
      the antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1381758
TI  - Candida onychomycosis--an evaluation of the candida species as primary
      keratinolytic yeasts in nail disease.
AB  - This is a pilot study of 5 nail specimens to evaluate the role of candida species
      in onychomycosis by taking pure isolates of different species of candida, growing
      these yeasts with normal nail keratin and assessing the growth of fungus
      periodically macroscopically and the final evaluation was made under electron
      microscope. The results suggest that the candida albicans primarily has an
      important role in keratolysis of nails.

PMID- 1381759
TI  - Oesophageal carcinoma caused by betel nut.

PMID- 1381760
TI  - Adenosine 3':5'-cyclic monophosphate inhibits in vitro angiogenesis induced by
      endothelial cell growth factor.
AB  - The formation of new blood capillaries (angiogenesis) occurs in response to
      angiogenic factors released by either normal or tumoral cells. In the present
      study, we cultured human umbilical vein endothelial cells (HUVEC) on collagen
      gels and aimed to clarify the effects of cyclic nucleotides on angiogenesis
      induced by endothelial cell growth factor (ECGF). HUVEC invaded the underlying
      collagen matrix and formed tube-like structures when ECGF was added. ECGF (9.4 to
      75 micrograms/ml) induced angiogenesis in a concentration-dependent manner; the
      effect reached a plateau at 75 micrograms/ml. Cyclic AMP (10(-3) M), dibutyryl
      cyclic AMP (10(-3) M), 8-bromo cyclic AMP (10(-5) M) and Sp-cAMPS (10(-3) M), a
      stimulator of cyclic AMP-dependent protein kinase, each significantly inhibited
      ECGF-induced angiogenesis by 64.2, 86.1, 46.5, 74.7%, respectively. Forskolin and
      cholera toxin, which are activators of adenylate cyclase, did not inhibit ECGF
      induced angiogenesis. Dibutyryl cyclic GMP (10(-4), 10(-3) M) also did not affect
      the formation of capillary-like tubes induced by ECGF. In conclusion, cyclic AMP,
      but not cyclic GMP, inhibits angiogenesis in vitro. This antiangiogenic activity
      may be applicable to the treatment of such conditions as solid tumors, diabetic
      retinopathy and rheumatoid arthritis in which the suppression of angiogenesis is
      important.

PMID- 1381761
TI  - Hemodynamic effects of cibenzoline on normal myocardium and after pretreatment
      with DL-sotalol.
AB  - The circulatory and myocardial effects of cibenzoline were investigated in 78
      open-chest rats during and after a 7-min intravenous (i.v.) infusion.
      Measurements were performed in the intact circulation, and myocardial function
      was also examined by isovolumic registrations independent of circulatory changes.
      In the first part of the study, the dose-dependent effects of cibenzoline were
      investigated (2, 4, and 8 mg/kg vs. NaCl controls). Cibenzoline caused a dose
      dependent decrease in heart rate (HR) (-16, -34, -37% vs. preinfusion values),
      mean aortic blood pressure (AoPm) (-8, -20, -30%), cardiac output (CO) (-6, -29, 
      39%), and dP/dtmax (+1, -21, -59%). The isovolumic peak left ventricular systolic
      BP (LVSBP) (-6, -6, -17%) and peak dP/dtmax (-8, -18, -54%) were also reduced. In
      the second part of the study, we examined the effects of 2 mg cibenzoline/kg
      after pretreatment with 2 mg DL-sotalol/kg: HR was -22% AoPm was -12%, CO was 
      29%, dP/dtmax was -40%, isovolumic LV pressure (LVP) was -12%, and peak dP/dtmax
      was -41%. Cibenzoline caused dose-dependent bradycardia, which cannot be
      explained by beta-adrenoceptor blockade. The auxotonic and isovolumic
      measurements indicate that cibenzoline possesses a dose-dependent negative
      inotropic effect: 2 mg cibenzoline/kg caused only a slight decrease in myocardial
      performance, but this effect was aggravated after pretreatment with DL-sotalol.
      Cibenzoline also increased peripheral resistance. The observed combination of
      negative inotropism and vasoconstriction caused by cibenzoline should be taken
      into consideration especially in patients with reduced LV function. This is of
      particular importance if cibenzoline is combined with DL-sotalol.

PMID- 1381762
TI  - Concentration/effect relationship and enantioselective analysis of verapamil in
      hypertensive patients.
AB  - The concentration/effect relationship of verapamil was analyzed in 9 hypertensive
      patients using concentrations of racemic verapamil and the corresponding decrease
      in mean arterial blood pressure (MBP) in a sigmoidal Emax model.
      Concentration/effect data were obtained after a first dose (240 mg sustained
      release preparation) and at steady state after stepwise dose adjustment to obtain
      satisfactory BP control (less than 90/150 mm Hg). Emax (MBP) ranged from 15 to 40
      mm Hg, and EC50 averaged 81 +/- 40 ng/ml (mean +/- SD). The fraction of S
      verapamil in the overall racemic verapamil concentrations was measured in two
      patients by chiral high-performance liquid chromatography (HPLC) and showed a
      slight increase at steady state from 12.2 +/- 1.5 to 14.4 +/- 1.4% and from 14.0
      +/- 1.3 to 16.3 +/- 0.6%. Concentration/effect curves for S-verapamil
      concentrations were similar to those obtained with racemic verapamil
      concentrations.

PMID- 1381763
TI  - Effects of nifedipine and indomethacin on cough induced by angiotensin-converting
      enzyme inhibitors: a double-blind, randomized, cross-over study.
AB  - Prostaglandins (PG) have been suggested to play a role in the genesis of cough
      induced by angiotensin-converting enzyme inhibitors (ACE-I) and that inhibition
      of PG synthesis can reduce or abolish the incidence of this side effect.
      Moreover, experimental and clinical data suggest that nifedipine, a
      dihydropyridine Ca antagonist, can inhibit PG synthesis. Therefore, we wished to
      determine whether nifedipine can reduce cough induced by ACE-I as compared with
      indomethacin, a known inhibitor of PG synthesis. Fourteen hypertensive patients
      who developed cough during captopril chronic therapy randomly received slow
      release nifedipine 20 mg twice daily (b.i.d.), indomethacin 50 mg b.i.d., and
      placebo b.i.d. for 1 week in a double-blind, cross-over design. At the end of
      each treatment phase, cough was evaluated by a self-administered questionnaire
      containing an ordinal scale for daily cough intensity and frequency. Indomethacin
      abolished or markedly reduced cough induced by ACE-I, whereas nifedipine reduced
      it but to a lesser degree. These findings suggest that PG can play a role in
      cough caused by ACE-I, and a dihydropyridine Ca antagonist can reduce the
      occurrence of this side effect.

PMID- 1381764
TI  - Selectivity of class I antiarrhythmic agents, disopyramide, pirmenol, and
      pentisomide for peripheral muscarinic M2 and M3 receptors.
AB  - The interactions of the class I antiarrhythmic agents, disopyramide, pirmenol,
      and pentisomide with peripheral muscarinic receptors were investigated by binding
      assay with [3H]N-methylscopolamine ([3H]NMS) as a ligand. All the agents
      inhibited the specific [3H]NMS binding to membrane preparations obtained from
      guinea pig submandibular gland (SG) and urinary bladder (UB) smooth muscle. The
      competition curves of these agents for [3H]NMS binding to SG membranes were
      monophasic, indicating competition with [3H]NMS at a single site. Comparison of
      results with those of our previous binding experiments using guinea pig left
      atrial (LA) membranes, showed that pirmenol had sevenfold lower affinity for
      glandular-type muscarinic receptors (M3) than for cardiac-type muscarinic
      receptors (M2). On the other hand, the dissociation constants (Ki) for
      disopyramide and pentisomide in SG were comparable to the high-affinity Ki values
      for these agents at M2 receptors. The competition curves of the three agents for
      [3H]NMS binding to UB membranes were biphasic and showed high- and low-affinity
      states of binding. The high- and low-affinity Ki values for pirmenol in UB were
      similar to its Ki values at M2 and M3 receptors obtained in LA and SG,
      respectively. The high-affinity Ki values for disopyramide and pentisomide were
      consistent with the respective Ki values determined in SG, whereas the low
      affinity binding sites for these agents were presumably the result of their
      allosteric interactions with the receptors. All agents at higher concentrations
      slowed the dissociation of [3H]NMS elicited by an excess of atropine in both UB
      and SG, thus indicating allosteric interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381765
TI  - Further observations to confirm the arrhythmia mechanism-specific effects of
      flunarizine.
AB  - In conscious dogs with chronic atrioventricular (AV) block, we recently
      demonstrated that flunarizine is effective against ouabain-induced arrhythmias
      (triggered activity resulting from delayed afterdepolarizations, DADs) but fails
      to suppress spontaneous ventricular tachycardias (VT) occurring 24 h after left
      anterior descending coronary artery occlusion (abnormal automaticity). Neither
      does flunarizine affect normal automaticity, which suggests that flunarizine
      could be used as a clinical tool to recognize cardiac arrhythmias based on
      triggered activity. To elucidate further the arrhythmia mechanism-specific action
      of flunarizine, we investigated (a) its hemodynamic and electrophysiologic
      effects in 6 anesthetized dogs, (b) its ability to prevent pacing-induced VT 7
      days after myocardial infarction (reentry) in 9 anesthetized animals, and (c) its
      effect on premature escape beats (PEBs) in 9 conscious dogs with chronic AV
      block. PEBs are probably caused by DADs. Flunarizine decreased systemic blood
      pressure (p less than 0.01), and left ventricular dP/dt (p less than 0.01), but
      did not affect AH or HV internal, QRS duration, QT time, or the effective
      refractory period of either AV node or right ventricle over a wide range of
      (paced) cycle lengths. Flunarizine decreased the inducibility of PEBs by 42% (p
      less than 0.01), but not that of the reentrant VT in any of the 6 inducible dogs.
      Therefore, we conclude that although flunarizine has no electrophysiologic
      effects in normal heart, it prevents induction of PEBs. The inability of
      flunarizine to prevent induction of reentrant VT confirms the mechanism-specific
      action of flunarizine against triggered activity.

PMID- 1381766
TI  - Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation
      to biologic effects in severe heart failure.
AB  - The pharmacokinetics of synthetic atrial natriuretic factor (ANF) and its effects
      on cyclic GMP, urinary sodium excretion, and hemodynamics were compared in 18
      control subjects with normal hemodynamics and 12 patients with severe heart
      failure. Human 99-126 ANF was administered intravenously (0.2 micrograms/kg i.v.
      followed by 0.07 micrograms/kg/min for 30 min). As compared with controls,
      baseline plasma ANF concentration was higher in the heart failure group (329.2 +/
      166.1 vs. 33.6 +/- 17.3 pg/ml in controls, means +/- SD, p less than 0.01).
      Synthetic ANF increased plasma ANF concentration by similar amounts, but the
      elimination half-life (t 1/2) for synthetic ANF was longer in the heart failure
      group (6.5 +/- 2.6 vs. 3.8 +/- 0.8 min, p less than 0.05). Baseline plasma cyclic
      GMP concentration was higher in the heart failure group (13.8 +/- 6.8 vs. 4.2 +/-
      2.2 pmol/ml, p less than 0.01) but ANF increased plasma cyclic GMP concentration
      to a lesser degree (14.4 +/- 7.6 pmol/ml, p less than 0.05 vs. 24.9 +/- 10.1
      pmol/ml, p less than 0.001). Baseline urinary sodium excretion was less in the
      heart failure group (13.3 +/- 14.0 vs. 53.7 +/- 37.3 mumol/min, p less than 0.01)
      and ANF induced a smaller increase in urinary sodium excretion (22.1 +/- 32.3
      mumol/min, p less than 0.05 vs. 305.7 +/- 242.9 mumol/min, p less than 0.001).
      Baseline plasma norepinephrine (NE), renin, and aldosterone were higher in the
      heart failure group. Synthetic ANF increased plasma NE only in the control group,
      had no effect on renin, and decreased aldosterone in both groups. Hemodynamic
      responses were similar in both groups except the decreased arterial blood
      pressure (BP) was accompanied by increased heart rate (HR) only in the controls.
      Therefore, in heart failure, the t 1/2 of ANF is prolonged and there appears to
      be a limit for further increase in cyclic GMP. These changes may explain in part
      the blunted renal response to ANF.

PMID- 1381767
TI  - Slow channel calcium blockers attenuate reoxygenation-mediated vascular
      contraction, but augment anoxia-mediated vascular contraction.
AB  - Anoxia and reoxygenation modulate vasomotor tone. To determine the effect of the
      slow channel calcium blockers verapamil and diltiazem in vascular smooth muscle
      contraction during states of altered oxygenation, rat aortic rings with intact
      endothelium were contracted with norepinephrine (NE) or the thromboxane A2 mimic
      U46,619 and then exposed abruptly to anoxia (switch from 95% O2 to 95% N2) for 30
      min and then reoxygenated (switch from 95% N2 to 95% O2). Anoxia caused a
      transient 40 +/- 9% (mean +/- SE, n = 15) increase in contraction, whereas
      reoxygenation resulted in an initial decrease followed by a large (83 +/- 21%)
      increase in contraction. Treatment of vascular rings with verapamil or diltiazem
      (1 microgram/ml or 2 microM) decreased contractile response to the agonists (p
      less than 0.01). Both these agents consistently augmented the magnitude and
      duration of anoxia-induced contraction (p less than 0.01). In other experiments,
      pretreatment of vascular rings with NG-monomethyl-L-arginine (L-NMMA), an
      inhibitor of endothelium-derived relaxing factor (EDRF) synthesis, or with
      oxyhemoglobin, an inhibitor of EDRF activity, or de-endothelialization resulted
      in marked (p less than 0.01) decrease in anoxic contraction, indicating that
      anoxia-induced contraction is caused by modulation of EDRF. Treatment of aortic
      rings with verapamil also reduced acetylcholine-mediated relaxation (from 86 +/-
      6% to 45 +/- 5%, p less than 0.02) and cyclic GMP accumulation (from 192 +/- 53
      to 111 +/- 35 fmol/mg, p less than 0.02), indicating reduction in EDRF synthesis
      or activity by verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381768
TI  - Adenosine increases total venous capacitance in awake instrumented rats.
AB  - To determine the effect of adenosine on the venous system, mean circulatory
      filling pressure (MCFP) was determined during infusion of intravenous (i.v.)
      adenosine (66.5 to a maximum of 532 microgram.kg-1.min-1) in 9 awake instrumented
      rats before and during ganglionic blockade with i.v. hexamethonium, 0.6 mg.kg
      1.min-1. MCFP, the equilibrated pressure (mm Hg) occurring when the circulation
      is arrested by transient inflation of a balloon in the right atrium, is inversely
      related to total venous capacitance. Both adenosine and hexamethonium caused a
      reduction in mean arterial pressure (MAP); heart rate (HR) decreased during
      adenosine infusion in the blocked, but not the unblocked, state. In the unblocked
      state, baseline MCFP was 6.5 +/- 0.3 mmHg; hexamethonium caused baseline MCFP to
      decrease to 5.3 +/- 0.3 mm Hg. In both the unblocked and the blocked state,
      adenosine caused a dose-related decrease in MCFP [6.5 +/- 0.3 to 5.5 +/- 0.6 mm
      Hg (532 microgram.kg-1.min-1 adenosine dose) unblocked state; and 5.3 +/- 0.3 to
      4.3 +/- 0.3 mm Hg (400 microgram.kg-1.min-1 adenosine dose) blocked state]. This
      decrease in MCFP induced by adenosine was highly significant. Intravenous
      adenosine, in an awake instrumented rat model, increases venous capacitance, with
      and without ganglionic blockade.

PMID- 1381769
TI  - Comparative effects of R 80122, enoximone, and milrinone on left ventricular
      phosphodiesterase isoenzymes in vitro and on contractility of normal and stunned
      myocardium in vivo in dogs.
AB  - Using different subtypes of cyclic nucleotide phosphodiesterase (PDE) isoenzymes
      isolated from canine left ventricle, we identified R 80122, a 1,2,3,5-tetrahydro2
      oxoimidazo[2,1-b]quinazoline derivative that was a more selective and potent
      inhibitor of PDE type III than milrinone or enoximone. Such substances improve
      cardiac contraction and relaxation, elicit vasodilation, and increase cardiac
      output (CO). To determine the extent to which these compounds affect the
      contractile force of stunned myocardium, the effects of enoximone, milrinone, and
      R 80122 on cardiac function were compared in anesthetized dogs subjected to 15
      min occlusion of the left anterior descending coronary artery (LAD) followed by
      reperfusion, and treated beginning 30 min after reperfusion, with the compound
      being studied. During occlusion, all dogs exhibited passive systolic ventricular
      wall bulging in the ischemic area. Thirty minutes after reperfusion, systolic
      wall thickening was significantly decreased in the reperfused LAD segments and
      remained low (at 36% of baseline) in control animals. After enoximone
      administration, global left ventricular (LV) function was improved with i.v.
      doses greater than or equal to 0.64 mg/kg. Systolic wall thickening in the
      ischemic myocardium was restored less than or equal to 70% of baseline at 1.25
      mg/kg i.v., but this dose also induced a marked decrease in arterial pressure and
      an increase in heart rate (HR). Milrinone and R 80122 significantly increased
      global LV function and systolic wall thickening in ischemic areas at doses
      greater than or equal to 0.16 mg/kg i.v. At the highest doses, HR increased
      slightly with both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381770
TI  - Increase in the hypotensive effect of bromocriptine induced by spinal transection
      in rats: contribution of spinal dopamine receptors.
AB  - Intravenous (i.v.) administration of bromocriptine (150 micrograms/kg) in
      conscious normotensive rats with chronic spinal cord transection (at T5-T7),
      pretreated or not with i.v. propranolol (0.5 mg/kg), induced significant
      decreases in mean arterial blood pressure (MAP) which were greater and longer
      lasting than those in intact rats (-15 to -20 as compared with -10 mm Hg) for 8
      days after transection. To assess the spinal and/or peripheral origin of this
      phenomenon, rats were also pretreated with either i.v. (0.3 mg/kg) or intrathecal
      (i.t.; 93 nmol/rat; at T9-T10) administration of domperidone, a selective
      dopamine (DA)2 receptor antagonist incapable of crossing the blood-brain barrier
      (BBB) freely. The increase in hypotension induced by spinal section was
      suppressed by i.t. but not by i.v. domperidone. In intact rats, bromocriptine
      elicited an increase in heart rate (HR; approximately 50 beats/min more), which
      was prevented by i.v. propranolol treatment. In spinal cord-transected rats,
      however, it had a significant bradycardic effect (approximately 50 beats/min
      less), which was antagonized by i.t.-administered domperidone. These results
      suggest that enhancement of the hypotensive effects induced by systemic
      administration of bromocriptine after a complete thoracic spinal transection is
      fully mediated by spinal DA2 receptors. This finding may help explain the
      increased orthostatic hypotension induced by DA receptor agonists in Parkinsonian
      patients with spinal lesions.

PMID- 1381772
TI  - Captopril modifies the response of infarcted rat hearts to isoprenaline
      stimulation.
AB  - In this study the effect of the angiotensin converting enzyme (ACE) inhibitor
      captopril on beta-receptor responsiveness was investigated in failing rat hearts
      after experimental myocardial infarction. Infarcted rats were treated for 8 weeks
      with either captopril added to the drinking water (100 mg/kg/day; n = 5) or
      drinking water alone (n = 7). Treatment was started 2-3 days before myocardial
      infarction. A third group of untreated rats without myocardial infarction served
      as control (n = 6). At the end of the treatment period the hearts were perfused
      as described by Langendorff, and a cumulative dose-response curve of isoprenaline
      was obtained in each heart. In comparison with noninfarcted hearts, the response
      of heart rate and peak pressure rate (dP/dt) to isoprenaline stimulation was
      significantly depressed in hearts of infarcted rats. Chronic treatment with
      captopril significantly attenuated the reduced responsiveness to isoprenaline
      stimulation. This improved responsiveness in captopril-treated rat hearts might
      be due to prevention of "down-regulation" of myocardial beta-adrenoceptors. Other
      factors should also be considered, such as prevention of structural alterations
      in the noninfarcted myocardium, e.g., myocardial hypertrophy and fibrosis.
      Differences in infarct size did not play an important role, since infarct size
      was comparable in both groups of infarcted rats. This partial preservation of
      beta-adrenergic responsiveness was accompanied by a significant reduction in
      right ventricular weight and lung weight, suggesting that captopril also improved
      the signs of heart failure. Therefore, the results of this study indicate that
      early ACE inhibition in myocardial infarction may be useful in preventing
      deterioration of cardiac function.

PMID- 1381771
TI  - The angiotensin converting enzyme inhibitor perindopril improves survival after
      experimental myocardial infarction in pigs.
AB  - In this randomized, blinded study the effect of the angiotensin converting enzyme
      inhibitor perindopril on electrical stability after myocardial infarction in pigs
      was compared to placebo. The left anterior descending artery was occluded for 45
      min. Perindoprilat (0.06 mg/kg, n = 12) or saline (n = 12) was injected 15 min
      before reperfusion. Treatment was continued till day 13 with perindopril (12 mg,
      once daily) or placebo. At day 14 an electrophysiologic study was performed. The
      release of creatine phosphokinase did not differ significantly. During the
      subsequent days, seven of 12 placebo-treated pigs died (six within 24 h), whereas
      two of the 12 perindopril-treated pigs died (one within 24 h; p less than 0.04).
      Sustained ventricular tachycardia was inducible in one of five placebo-treated
      pigs versus three of 10 perindopril-treated survivors (NS). Late potentials had
      developed in one placebo-treated pig but not in pigs that received perindopril.
      Characteristics of infarct border zone heterogeneity (percentages of a reference
      electrode in viable myocardium) such as a dispersion of current thresholds (127
      +/- 96 vs. 238 +/- 463% in perindopril-treated pigs, NS) and refractoriness (9.8
      +/- 8.4 vs. 11.9 +/- 6.0% in perindopril-treated pigs, NS) were comparable. This
      treatment with perindopril significantly improved survival while electrical
      stability was comparable between survivors. The latter indicates that a
      comparable electrical stability 2 weeks after myocardial infarction is obtained
      in perindopril-treated pigs at a significantly higher survival rate.

PMID- 1381773
TI  - Antiarrhythmic effects of the angiotensin converting enzyme inhibitor
      perindoprilat in a pig model of acute regional myocardial ischemia.
AB  - Previous studies on the possible antiarrhythmic effects of angiotensin converting
      enzyme (ACE) inhibitors during early ischemia in pigs have been inconclusive or
      negative; however, proof of adequate ACE inhibition was not provided.
      Perindoprilat, 0.06 mg/kg, i.v., was administered 30 min prior to ligation of the
      anterior descending coronary artery (CAL) in anesthetised open-chest pigs. Plasma
      ACE activity was decreased by 95.0 +/- 1.9% when measured 5 min before CAL.
      Within 5 min of CAL, the ventricular fibrillation threshold (VFT) in the control
      group was decreased from 11.8 +/- 1.9 to 7.2 +/- 1.2 mA (p less than 0.01).
      Perindoprilat prevented the fall in the VFT and the increase in left ventricular
      end-diastolic pressure caused by CAL. Perindoprilat decreased arterial pressure.
      Cardiac output (thermodilution) was decreased by 23 +/- 3% after CAL in the
      control group and by only 10 +/- 5% (p less than 0.05) in the perindoprilat group
      (both versus pre-CAL values). In the control group cyclic AMP was increased from
      0.97 +/- 0.04 (pre-CAL) to 1.16 +/- 0.04 nmol/g (p less than 0.05) in the central
      ischemic zone 20 min after CAL. Perindoprilat prevented this increase in cyclic
      AMP. Twenty minutes after CAL blood flow (microsphere method) in the nonischemic
      zone of the perindoprilat group was increased, whereas blood flow in the central
      ischemic zone was decreased compared to the control group. However, levels of
      tissue metabolites (ATP, phosphocreatine, lactate) measured in drill biopsies in
      the same zones of the two groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381774
TI  - Effects of nitroglycerin on the coronary microcirculation in normal and ischemic
      myocardium.
AB  - Nitroglycerin dilates conduit coronary vessels and only transiently increases
      flow, however the effects of nitroglycerin in the microcirculation of normal
      myocardium and during myocardial ischemia have not been assessed. The goal of
      this investigation was to determine the effects of steady-state levels of
      nitroglycerin on the microcirculation of normal and ischemic myocardium.
      Microvessels on the left ventricle were viewed using stroboscopic epi
      illumination in anesthetized, open-chest dogs. Myocardial perfusion was measured
      with radioactive microspheres. Aortic pressure and heart rate were kept constant
      by an aortic snare and left atrial pacing. Microvessel diameters were measured
      under control conditions and during steady-state infusion of nitroglycerin (n =
      11, 0.01-100 micrograms kg-1 min-1, i.v.). Nitroglycerin selectively dilated
      arteries from 201 to 386 microns, but had no effect on large arterioles less than
      200 microns. Total coronary vascular resistance remained constant except at the
      highest dose. When mean coronary pressure was decreased to 35 mm Hg, small
      arterioles less than 100 microns dilated. Diameters of larger arterioles
      decreased. Nitroglycerin (10 micrograms kg-1 min-1, i.v., n = 8) selectively
      dilated microvessels greater than 200 microns in the region distal to the
      stenosis, although myocardial perfusion was not affected. Thus, nitroglycerin
      altered the distribution of microvascular resistance without altering overall
      resistance. We conclude that steady-state infusion of nitroglycerin selectively
      dilates coronary arterial microvessels greater than 200 microns. During decreased
      perfusion pressure, recruitable vasodilation in response to nitroglycerin is due
      to dilation of microvessels greater than 200 microns.

PMID- 1381775
TI  - Effect of age on endothelin-1 binding sites in rat cardiac ventricular membranes.
AB  - To establish whether the density, affinity, or selectivity of endothelin-1 (ET-1)
      binding sites in cardiac ventricular membranes varies with age, membranes were
      harvested from 5- to 7-day-, 20-day-, and 8- to 9-week-old Sprague Dawley rats
      and labeled with [125I]ET-1. Selectivity was established by using cold ET-1, ET
      2, ET-3, big ET-1, and (+)PN200-110 to inhibit specific binding of [125I]ET-1.
      Over the age span studied, selectivity and affinity of the [125I]ET-1 binding
      sites was unchanged, but density (Bmax) decreased from 209.7 +/- 18.4 at 5-7 days
      to 154.0 +/- 8.9 (p less than 0.02) at 20 days, and to 89.7 +/- 5.2 (p less than
      0.01) fmol/mg protein at 8-9 weeks. These age-dependent differences in Bmax were
      not accompanied by a change in membrane yield and occurred at a time when the
      specific binding of (+)[3H]PN200-110 increased.

PMID- 1381776
TI  - Chronic adriamycin treatment and its effect on the cardiac beta-adrenergic system
      in the rabbit.
AB  - Treatment of male rabbits with adriamycin at a cardiotoxic dose (1 mg/kg
      intravenously, i.v., twice a week for 9 weeks) caused cardiovascular disturbances
      characteristic of chronic heart failure. The severity of symptoms varied,
      indicating differences in the individual sensitivity of the animals to
      adriamycin. Thus, cardiac output (CO) was decreased by greater than 40% in only 4
      of the 7 animals in which it was measurable at 9 weeks. Elevated levels of atrial
      natriuretic factor (ANF) and plasma renin activity (PRA), as well as pulmonary
      congestion, hydrothorax, and ascites were also evident. The baroreflex response
      to sodium nitroprusside (NPS) was blunted. The response to the inotropic drug
      dobutamine was depressed by 50% as compared with the control animals. Right
      ventricular beta-adrenoceptor density was significantly reduced in these animals
      (22.9 +/- 3.1 as compared with 31.8 +/- 1.0 fmol/mg protein in control animals)
      owing to a selective downregulation of the beta 1-adrenoceptor population. The
      loss of beta-adrenoceptors was highly correlated with severity of heart failure
      symptoms: i.e., baroreflex dysfunction as indicated by the NPS slope (r = 0.91),
      decrease in CO during the previous weeks (r = 0.88), and plasma norepinephrine
      (NE) levels (r = 0.96). However, when all adriamycin-treated animals were
      compared collectively regardless of the severity of heart failure, with the
      controls, no difference in the beta-adrenoceptor density was detectable, a
      finding in agreement with previous observations in this model. Chronic treatment
      of rabbits with adriamycin thus causes low-output failure, reflecting some of the
      findings reported for the human disease; however, individual sensitivity to
      adriamycin varies considerably between rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381777
TI  - Cardiotonic and coronary vasodilator responses to milrinone, forskolin, and
      analog P87-7692 in the anesthetized dog.
AB  - Forskolin and milrinone both increase cyclic AMP concentrations to enhance
      cardiac contractility and cause vascular dilation in vitro and in vivo. However,
      forskolin acts via direct stimulation of adenylate cyclase while milrinone
      inhibits phosphodiesterase (PDE-III) activity. The forskolin analog, 7-desacetyl
      7-(O-propionyl)-hydroxyl-aminocarbonyl-forskolin (P87-7692) has also been shown
      to directly stimulate adenylate cylase and increase cyclic AMP production in
      isolated cardiac tissue; however, the in vivo activity of this compound has not
      been described. Thus, the purpose of this study was to compare the cardiovascular
      effects of equivalent doses of these compounds and to further characterize the
      cardiotonic activity of P87-7692 in the anesthetized dog. It was found that both
      i.v. (3-30 micrograms/kg) and intracoronary (0.1-30 micrograms) administration of
      milrinone, forskolin, and P87-7692 caused dose-related positive inotropic,
      coronary, and peripheral vasodilator effects in anesthetized dogs; however, P87
      7692 produced significantly greater and more sustained cardiotonic activity
      following a single 30-micrograms/kg, i.v., bolus injection when compared to the
      same dose of milrinone and forskolin. Analysis of the dose-response relationship
      between the changes in contractile force and heart rate for these compounds
      revealed that a 50% augmentation in contractile force was associated with
      increases in heart rate of 2.1% for milrinone, 6.4% for P87-7692, and 13.7% for
      forskolin. These data indicate an improved separation between the chronotropic
      and inotropic effects for P87-7692 as compared to forskolin. All three compounds
      also produced coronary vasodilation in vivo and in vitro; however, P87-7692
      consistently showed greater activity relative to the same doses of milrinone and
      forskolin. Moreover, P87-7692 was significantly (p less than 0.05) more potent at
      relaxing KC1-precontracted canine coronary rings, with an EC50 of 2.1 x 10(-7) M
      as compared to 1.1 x 10(-6) M for forskolin and 3.2 x 10(-6) M for milrinone. The
      results of these studies indicate that structural modification of the forskolin
      molecule can increase the separation between positive inotropic and chronotropic
      effects, improve the overall hemodynamic profile, and prolong the duration of
      cardiotonic activity for this class of compounds.

PMID- 1381779
TI  - Epicardial controlled-release verapamil prevents ventricular tachycardia episodes
      induced by acute ischemia in a canine model.
AB  - Sustained-release preparations composed of verapamil-polymeric controlled-release
      matrices were characterized in vitro and utilized as epicardial implants in dogs
      with ischemic ventricular arrhythmias. Anesthetized open-chest dogs were
      subjected to 5 hourly, 10-min complete occlusions of the left anterior descending
      coronary artery followed by reperfusion. A controlled-release matrix preparation
      (20% verapamil, 80% polyurethane), placed on the left ventricular epicardium
      prior to the third occlusion, resulted in successful inhibition of ventricular
      tachycardia (VT) during acute ischemia in a dose-dependent manner. The largest
      matrix size used, 300 mg (20% verapamil), provided a net systemic dose of 0.52 +/
      0.18 mg/kg over 140 min and significantly reduced VT episodes during acute
      ischemia (fifth occlusion) compared to untreated controls (0.16 +/- 0.04 vs. 1.01
      +/- 0.35 episodes/min, respectively; t = 2.62, p = 0.01). In controls, by the
      fifth occlusion ventricular fibrillation (VF) occurred after 5.41 +/- 0.78 min in
      89% of animals. However, after a 300-mg verapamil matrix was placed on the left
      ventricular ischemic zone, VF occurred in only 45% (chi-squared = 4.1, p = 0.04,
      vs. controls) of the animals after 7.87 +/- 0.92 min (fifth occlusion). Systemic
      venous plasma verapamil levels during the 2 h following the 300-mg matrix
      ischemic zone implantation ranged from 8.4-22.0 ng/ml, while simultaneous
      regional coronary venous levels were 125.0-387.0 ng/ml. Sonomicrometry studies of
      left ventricular wall thickening carried out with a series of 300-mg verapamil
      matrix cardiac implants did not demonstrate any significant myocardial
      dysfunction. It is concluded that controlled-release verapamil, administered
      directly to the heart, was effective for preventing VT and VF associated with
      acute coronary ischemia, and that this route of administration was not associated
      with any significant deterioration of cardiac function.

PMID- 1381778
TI  - Cerebral vasodilating and spasmolytic actions of a new Ca-antagonist, clentiazem
      (TA-3090), in anesthetized animals.
AB  - The effect of a new 1,5-benzothiazepine calcium antagonist, clentiazem (TA-3090),
      on the cerebral circulation was studied in anesthetized animals. Intravenous
      infusion of clentiazem at doses of 2.5, 5, and 10 micrograms/kg/min increased
      vertebral blood flow without causing hypotension in anesthetized dogs. After i.v.
      injection to anesthetized dogs, clentiazem, diltiazem, and papaverine all dose
      dependently increased the regional cerebral blood flow and raised the
      intracranial pressure (ICP). However, the effect of clentiazem on the ICP was
      weaker than that of diltiazem and papaverine. In anesthetized monkeys, clentiazem
      (3-100 micrograms/kg, i.v.) increased the internal carotid blood flow to the
      intracranial tissues. In anesthetized cats, topical or i.v. clentiazem inhibited
      basilar artery vasospasm induced by the topical application of serotonin,
      prostaglandin F2 alpha, and incubated blood. These findings suggest that
      clentiazem has favorable properties as a cerebral vasodilator.

PMID- 1381780
TI  - A proarrhythmic response to sodium channel blockade: modulation of the vulnerable
      period in guinea pig ventricular myocardium.
AB  - The vulnerable period (VP) is an interval of time during the cardiac cycle within
      which premature stimulation may lead to trains of responses (one: many stimulus
      response coupling). Although the VP parallels the recovery of sodium channel
      availability, modulators of its boundaries remain unclear. Numerical studies of a
      uniform cable demonstrated that reduction in sodium channel availability
      increased the range of premature stimuli, resulting in unidirectional block, a
      precursor of reentrant activation. Consequently, we hypothesized that the
      kinetics of use-dependent sodium channel blockade could reflect one dimension of
      a drug's proarrhythmic potential. In strips from guinea pig right ventricle, we
      probed the boundaries of the VP in the presence of use-dependent sodium channel
      antagonists utilizing a train of stimuli followed by a premature stimulus. Under
      drug-free conditions when the sites of drive and premature stimulation were the
      same, the VP was less than 4 ms in duration. When the drive and premature sites
      were different, the drug-free VP was greater than 5 ms in 22 of 24 preparations
      and 0 in the other two, with an average VP duration of 16 +/- 10 ms (mean +/-
      SD). In the presence of 1 microM moricizine, VP = 17 +/- 4 ms; 12 microM
      moricizine, VP = 35 +/- 4 ms; 3 microM flecainide, VP = 50 +/- 17 ms; and 4
      microM quinidine, VP = 2 +/- 1 ms. These results suggest that residual
      unsuppressed premature ventricular contractions (PVCs) in the presence of some
      class 1 drugs have a greater potential for initiating a proarrhythmic response
      than PVCs in the absence of a class 1 drug.

PMID- 1381782
TI  - Contribution of delayed rectifier and inward rectifier to repolarization of the
      action potential: pharmacologic separation.
AB  - Outward potassium (K) currents contribute to the repolarization process of
      cardiac action potentials. There are, however, multiple K currents. Recently, two
      putatively specific K channel blockers have been developed as potential class III
      antiarrhythmic agents. E-4031 appears to block specifically a fast component of
      the delayed rectifier (IK), and RP 58866 is a reported inward rectifier current
      (IK1) blocker. In the present experiments, we examined the effects of E-4031 and
      RP 58866 on action potentials recorded from guinea pig papillary muscles to
      determine whether the properties of IK and IK1 measured in whole-cell experiments
      would be manifested in distinct effects. Both compounds prolonged the APD50
      (action potential duration at 50% repolarization) and APD90 (action potential
      duration at 90% repolarization). However, RP 58866 did not significantly prolong
      the action potential at voltages of 0 mV and above, while E-4031 did. The results
      suggest that preferential IK1 block results in a change in action potential
      waveform that is distinct from that resulting from block of other outward K
      currents. This could thus be used as a simple first-pass screening tool in
      determining a preliminary mechanism of action of class III antiarrhythmics prior
      to more time-consuming but necessary whole-cell voltage clamp experiments.

PMID- 1381781
TI  - Effects of interleukin-1 receptor antagonist on three types of responses to
      interleukin-1 in rabbit isolated blood vessels.
AB  - Interleukin-1 receptor antagonist (IRA) is a secretory product of human monocytes
      or related cell lines that acts as a pure interleukin-1 (IL-1) antagonist in
      several bioassays. IRA administration was reportedly a life-saving intervention
      in rabbits injected with lethal doses of bacterial lipopolysaccharide (LPS). We
      report the inhibitory effect of IRA on three distinct types of vascular responses
      to IL-1 in rabbit isolated blood vessels. The rabbit isolated superior mesenteric
      artery, when precontracted with phenylephrine, relaxed in a sustained manner in
      less than 30 min following application of recombinant interleukin-1 beta (12-290
      pM), and this was a prostaglandin (PG)-dependent and endothelium-independent
      process. IRA (human recombinant sequence; 0.9-15 nM) behaved as an antagonist of
      IL-1 alpha or IL-1 beta, based on the surmountability and the concentration
      dependence, but could only prevent the effect of IL-1, not reverse it. IRA had no
      direct effect on the preparation and did not influence the acute relaxing effect
      elicited by substance P or iloprost, a PGI2 mimetic. Exposure to IL-1 beta
      depressed the response to noradrenaline (NA) in several hours in rabbit aorta
      rings. The inhibitory effect of IL-1 beta was endothelium and prostaglandin
      independent, but was prevented by a treatment with NG-nitro-L-arginine (a nitric
      oxide synthesis inhibitor), cycloheximide, dexamethasone, or IRA. Using the
      residual NA-induced contraction as a quantification of the IL-1 agonist effect,
      IRA was a very potent antagonist of IL-1 beta but was not totally
      surmountable.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381783
TI  - ACE inhibitors and end-organ damage in cardiovascular disease: vessel-wall damage
      and cardiac function in hypertension. Proceedings of the Erasmus Medical
      Workshops.

PMID- 1381785
TI  - Role of arterial compliance in the physiopharmacological approach to human
      hypertension.
AB  - Arterial compliance in humans is generally measured by modeling analysis of pulse
      tracing or of pulse wave propagation in the arterial tree. It is decreased in
      hypertension in part because elevation of blood pressure stiffens the arteries by
      stretching the rigid collagen fibres of their walls. Using a modeling evaluation
      of the compliance-pressure relationship in large arteries, it is possible to
      correct compliance from the mechanical effect (passive effect) due to pressure
      elevation. This makes it possible to show that, at the same pressure as in normal
      controls, hypertensive patients maintain decreased arterial compliance. This
      finding suggests that functional and/or structural changes other than pressure
      mediated stretching of arteries (active effect) contribute toward reducing
      arterial compliance. Thus, the response of compliance to antihypertensive drugs
      must be studied by differentiating between passive and active effects. The
      diameter and compliance-pressure relationship in arteries allow differentiation
      of a passive arterial effect due to the pressure-lowering action of the drug, and
      an active pharmacological effect calculated at the same pressure before and after
      drug administration. Four drugs--ketanserin, urapidil, nitrendipine, and
      nicardipine (acute administration)--are given as examples. No active or passive
      compliance changes are observed with urapidil and ketanserin. In contrast, an
      active increase in compliance is observed in isobaric conditions with calcium
      antagonists, together with large-artery dilation due to a potent smooth muscle
      relaxing effect. This active increase in compliance is potentiated by a passive
      increase due to the pressure-lowering effect that reduces the mechanical stretch
      exerted by blood pressure on arterial bioelastomers. Finally, an optimum increase
      in arterial compliance is achieved by drugs that vasodilate large arteries by
      smooth muscle relaxation and concomitantly decrease blood pressure. This may be
      of importance because low compliance has adverse effects on the cardiovascular
      system by contributing to the pathogenesis of systolic hypertension and left
      ventricular hypertrophy. Loss of arterial compliance may also be an early marker
      of atherosclerosis.

PMID- 1381784
TI  - Determinants of vascular structure.
AB  - The development of the vasculature is a complex process, the end result of which
      enables the cardiovascular system to supply each tissue with the required amount
      of blood at the correct pressure. The mechanisms controlling this development are
      poorly understood, and this article seeks to review briefly some of the
      mechanisms that may be involved. At the capillary level, it appears that
      capillary proliferation is closely related to tissue metabolism. The lumen
      diameter of the feeding arterioles and arteries then develops (through a
      mechanism that appears to be dependent on endothelial factors) to accommodate the
      new flow requirements. In studies of the development of esophageal varices, it
      seems that the increased lumen diameter resulting from increased flow is due to
      the rapid synthesis of wall material. Within the walls of the feeding arterioles
      and arteries, the smooth muscle develops to insure a constant loading of the
      individual smooth muscle cells. This development is not necessarily associated
      with alterations in the amount of smooth muscle, but can be due to "remodeling,"
      i.e., the rearrangement of existing smooth muscle cells to allow them to perform
      their function more effectively. Clearly, if we assume that antihypertensive
      therapy should seek not only to reduce blood pressure but also to normalize
      vascular structure, a better understanding of the mechanisms controlling vascular
      development is needed.

PMID- 1381786
TI  - Systolic and diastolic cardiac function in hypertension.
AB  - Hemodynamic variables in hypertension are governed in part by pressure-volume
      relationships that in turn can be subdivided between systolic and diastolic
      cardiac functions. These variables are of great consequence when screening
      patients with high blood pressure, in particular in the early stages. Both
      systolic and diastolic cardiac function, now detectable by echocardiography, can
      be affected by antihypertensive agents. Against this background, various
      antihypertensives gain significance, as in addition to their blood pressure
      lowering effect they may also change detrimental metabolic and (para-) endocrine
      variables associated with hypertension.

PMID- 1381787
TI  - Effects of antihypertensive therapy on diastolic dysfunction in left ventricular
      hypertrophy.
AB  - In systemic hypertension, a certain degree of impairment of left ventricular
      diastolic function is often detectable, and is the consequence of two factors:
      elevated afterload and left ventricular hypertrophy. The goal of improving
      diastolic dysfunction can thus be achieved by lowering blood pressure and by
      inducing a regression in left ventricular hypertrophy. A reduction in blood
      pressure by intravenous administration of verapamil has proved capable of
      enhancing left ventricular filling properties in patients with hypertension. This
      finding has not been corroborated, however, in midterm protocols using an array
      of drugs (beta-blockers, dihydropyridines, diltiazem, and diuretics). Reduction
      in left ventricular mass can be achieved by several categories of drugs, and it
      has been shown that a decrease in mass is accompanied by an improvement in the
      early diastolic filling pattern. The kind of drug used to accomplish mass
      reduction seems to be irrelevant as far as the improvement in diastolic function
      is concerned. The pattern of left ventricular hypertrophy, however, might play a
      role in influencing the outcome on diastolic mechanics of left ventricular mass
      decrease.

PMID- 1381788
TI  - The effects of antihypertensive medications on the physiological response to
      maximal exercise testing.
AB  - This study compared the effects of clinically prescribed doses of cilazapril,
      nifedipine, and atenolol on maximal exercise performance in physically active
      subjects. In a double-blind crossover trial, 10 healthy male volunteers performed
      progressive aerobic exercise to exhaustion for determination of maximal oxygen
      consumption (VO2 max), after single dose ingestion of cilazapril, nifedipine,
      atenolol, and placebo. Measurements were made at exhaustion and at a single
      submaximal workload (250 W). Exercise time to exhaustion and peak workload were
      decreased by all agents (p less than 0.05 vs. placebo), but VO2 max was decreased
      by atenolol only (p less than 0.05 vs. placebo). Although both atenolol and
      cilazapril decreased the maximum systolic blood pressure, the peak heart rate was
      decreased only by atenolol (p less than 0.001 vs. placebo). Whereas submaximal
      oxygen consumption, minute ventilation, and blood lactate concentrations were not
      different between groups, ratings of perceived exertion were increased during
      submaximal exercise by atenolol and cilazapril (p less than 0.05 vs. placebo).
      Cilazapril, nifedipine, and atenolol all impaired exercise performance and
      increased ratings of perceived exertion during submaximal exercise without
      altering rates of oxygen consumption or blood lactate accumulation. Maximal
      exercise performance was impaired to a greater extent by atenolol than by
      nifedipine or cilazapril. This study suggests that either angiotensin-converting
      enzyme inhibitors or calcium-channel antagonists might be preferable for the
      management of hypertension in athletic patients as they have a lesser effect on
      exercise performance, at least in healthy individuals.

PMID- 1381789
TI  - Acute effects of cilazapril on coronary hemodynamics in patients with
      renovascular hypertension.
AB  - The effects of converting enzyme inhibition on coronary and systemic hemodynamics
      in the presence of a chronically activated renin-angiotensin system were
      investigated in five renovascular hypertensive patients with no
      ECG/echocardiographic evidence of left ventricular hypertrophy. Coronary blood
      flow (CBF, thermodilution technique), intra-arterial blood pressure, AVO2
      difference (coronary sinus), heart rate, and coronary vascular resistance were
      measured at rest, during isometric exercise (handgrip to 50% of maximal effort
      for 3 min) before and 60 min after 2.5 mg of oral cilazapril. The drug induced a
      prompt, significant decrease in mean arterial pressure and a sustained increase
      in CBF. The performance of handgrip after cilazapril resulted in higher increases
      in CBF for a given increase in myocardial oxygen requirements. These observations
      suggest that angiotensin II (Ang II) maintains the ability to alter the control
      mechanisms of CBF even under long-term conditions and that converting enzyme
      inhibition reverses the Ang II-induced effects on coronary hemodynamics.

PMID- 1381791
TI  - Role of angiotensin-converting enzyme inhibitors in preventing or reducing end
      organ damage in hypertension.
AB  - Angiotensin-converting enzyme inhibitors have been shown to be effective therapy
      for hypertension, and also for severe congestive heart failure, whether due to
      hypertension or to other causes. The reduction in cardiac hypertrophy that
      follows the use of these drugs is undoubtedly due in part to their favorable
      hemodynamic effects of reducing peripheral resistance and inducing venodilation.
      The same factors reduce cardiac dilation and left ventricular remodeling after
      myocardial infarction. The prevention of the hemodynamic effects of angiotensin
      II (Ang II) is probably the major factor in preventing end-organ damage, but
      there are some indications that Ang II may have an effect independent of blood
      pressure in promoting vascular hypertrophy. The separation of vasoconstrictor
      effects from any metabolic effects of Ang II is not easy, and final elucidation
      of the mechanisms involved is not yet available.

PMID- 1381790
TI  - Effects of converting enzyme inhibitors on coronary flow and myocardial ischemia.
AB  - The regulation of coronary hemodynamics is a complex process. One important
      factor that interferes with the regulation of coronary tone is the
      pathophysiological state of the vessels: stimuli that in normal vessels provoke
      no or only a slight vasoconstriction may cause a severe vasoconstriction in
      diseased vessels. This effect is related to the function of the endothelium and
      its ability to produce nitric oxide and prostaglandins. The presence of a local
      renin-angiotensin system implies the possibility of influencing the coronary flow
      via interference with this local system. Therefore, it is interesting to
      determine the effects of converting enzyme inhibitors on coronary flow. In animal
      experiments, a bradykinin-dependent coronary vasodilation by angiotensin
      converting enzyme (ACE) inhibitors is suggested. However, reports on the effect
      of converting enzyme inhibitors in patients with angina pectoris are not
      consistent. Some authors found an increase in coronary flow and others found no
      change or a decrease. The importance of the activation of the renin-angiotensin
      system is discussed. Moreover, it is shown that captopril reduces sympathetic
      mediated coronary vasoconstriction during the cold pressor test and that
      captopril enhances the parasympathetic-mediated bradycardia during the diving
      response. In conclusion, the effects of converting enzyme inhibitors on coronary
      flow is an interesting but not fully understood topic. Therefore, the
      multifactorial mechanism of action of converting enzyme inhibitors deserves
      further investigation. There are probably subgroups of anginal patients who may
      benefit from converting enzyme inhibitor therapy. These subgroups have to be
      defined. Especially, the finding that a converting enzyme inhibitor reduces
      sympathetically induced coronary vasoconstriction seems promising.

PMID- 1381793
TI  - Endothelium-dependent regulation of resistance arteries: alterations with aging
      and hypertension.
AB  - Small arteries with a diameter of 200 microns or less play an important role in
      the regulation of peripheral vascular resistance. Dysregulation of vascular tone
      of these arteries may contribute significantly to high blood pressure. The
      contractile state of blood vessels is regulated by peripheral neurons, vascular
      smooth muscle, and the endothelium. In perfused mesenteric resistance arteries of
      the rat, removal of the endothelium markedly augments the sensitivity and maximal
      response to norepinephrine and endothelin-1. Acetylcholine causes profound
      endothelium-dependent relaxation of resistance arteries contracted with
      norepinephrine or endothelin-1. The potency of the muscarinic agonist is
      particularly pronounced with intraluminal application. The inhibitory effects of
      the endothelium against contractions induced by norepinephrine and endothelin-1
      are reduced with aging and hypertension. The endothelium-dependent relaxation in
      response to intraluminal, but not extraluminal, acetylcholine is blunted in
      mesenteric resistance arteries of hypertensive rats and in the forearm
      circulation of hypertensive patients studied in vivo. The sensitivity of vascular
      smooth muscle to the effects of endothelin decreases with advancing age and in
      the spontaneously hypertensive rat. Thus, endothelium-derived vasoactive
      substances can profoundly affect vascular tone of resistance arteries studied in
      vitro and in vivo. The inhibitory effects of the endothelium against
      vasoconstrictor stimuli decreases with aging and hypertension, indicating a
      dysfunction of these regulatory mechanisms under these conditions.

PMID- 1381792
TI  - Vascular protection with cilazapril in hypertension.
AB  - Anatomical changes of arteries and arterioles secondary to hypertension explain
      most of the late complications of this disease. Therefore, a series of
      experiments was performed to characterize the vascular protective effects of
      cilazapril in experimental hypertension. These experiments aimed to answer three
      types of questions: (a) In which vascular bed is cilazapril effective? (b) Are
      the vascular changes induced by cilazapril associated with functional effects?
      (c) Is the effect of cilazapril only preventive or can cilazapril also be
      effective when hypertension is already present? Our results show that cilazapril
      is acting on nearly every vascular bed. Its vascular morphological effects
      (decrease of vascular hypertrophy) are associated with functional changes such as
      improvements of coronary or cerebral vascular reserves. Cilazapril is active
      either as a preventive treatment or given when hypertension is already present.

PMID- 1381795
TI  - The molecular basis of cardiovascular hypertrophy: the role of the renin
      angiotensin system.
AB  - Factors that can influence cardiovascular growth are becoming increasingly
      important for our understanding of such complex diseases as cardiac hypertrophy,
      coronary artery disease, atherosclerosis, and hypertension. Several proto
      oncogenes were found to be involved in the regulation of abnormal cell growth in
      cardiovascular disease. It is also evident that some peptide hormones, which are
      well known to be involved in blood pressure control, may play a role as growth
      modulators. Angiotensin II is one such peptide. It elevates blood pressure
      through its direct vasoconstrictor, sympathomimetic, and (through release of
      aldosterone) sodium-retaining activity but also appears to have mitogenic
      actions. Interestingly, all components of the renin-angiotensin system were found
      locally in cardiovascular tissues. The question remains whether angiotensin can
      act directly as a growth factor or whether it does so indirectly by influencing
      or modulating cell growth factors. A better understanding of the renin
      angiotensin system as a direct or indirect mediator for cardiovascular
      hypertrophy would offer new and interesting insights into the pathophysiology of
      hypertension and possibly novel options for the treatment of cardiovascular
      disease.

PMID- 1381794
TI  - Determining hypertensive end-organ damage in trials: a review of current
      methodologies and techniques.
AB  - The determination of hypertensive end-organ damage is the most crucial aspect of
      any long-term hypertension trial. Definition of inclusion criteria and withdrawal
      rules, and the evaluation of the treatment regimen in light of the cardiovascular
      prognosis, are all largely dependent on the trialists' abilities to identify
      vascular lesions and/or functional deteriorations of the major target organs.
      Although the vascular complications of hypertension tend to be diffuse, some
      organs and tissues are particularly sensitive: brain, eye fundus, heart, conduit
      arteries, and kidneys. To achieve a modicum of diagnostic accuracy, trial
      investigators will have to combine clinical acumen with a selection of ancillary
      techniques. This article reviews the compromises resulting from weighing the
      available technological potential against such conflicting factors as convenience
      and compliance of trial subjects, and expenditure.

PMID- 1381796
TI  - Hypertensive heart disease: pathophysiology and clinical and prognostic
      consequences.
AB  - The determinants of cardiac output were investigated in 161 patients with
      essential hypertension World Health Organization (WHO) stages I and II. In
      multiple regression analysis, cardiac output was inversely and independently
      related to blood pressure and to age. In patients with more severe hypertension,
      the lower cardiac output was associated with a lower stroke volume and a higher
      peripheral oxygen extraction. When age and blood pressure were taken into
      account, cardiac output was not a significant predictor of total mortality and of
      future cardiovascular events. Clinic and casual blood pressure explain only up to
      about 30% of the variability of echocardiographic left ventricular mass. The
      relationship of electrocardiographic voltages with blood pressure at various
      levels of bicycle exercise was highly significant in 169 patients with essential
      hypertension (r = 0.29-0.38; p less than 0.001) but the relationship was not
      better than with pressure at rest (r = 0.39). Ambulatory blood pressure, however,
      may be better related to left ventricular mass than clinic pressure. Several
      studies indicate that left ventricular hypertrophy is a significant risk factor
      for future cardiovascular events, independent of age and blood pressure. Left
      ventricular systolic function is usually normal in established hypertension, but
      diastolic function is frequently impaired, which could explain the reduced peak
      oxygen uptake in patients with more severe hypertension.

PMID- 1381797
TI  - The concept of coronary flow reserve.
AB  - Coronary reserve has been defined as the ratio of coronary resistance under
      control (rest) conditions and of coronary resistance after maximal coronary
      vasodilation. The latter can be achieved by various interventions, the most
      important and clinically relevant example being intravenous administration of
      dipyridamole at 0.5 mg/kg of body weight. For patients without coronary artery
      disease, the coronary reserve is about 400 to 500%, i.e., the normal heart is
      capable of reducing its coronary resistance to minimal values of 0.18 to 0.2 mm
      Hg/ml/min/100 g or to increase coronary flow by approximately four- to fivefold.
      The determination of coronary reserve in humans implies the availability of
      adequate methods. Systematic analyses of different coronary blood flow
      measurements have proved the gas chromatographic argon method to be the most
      appropriate and accurate method for clinical conditions, as previously described
      in detail. In this report, our findings on the coronary reserve analysis in
      various clinical conditions are described as follows: (a) coronary artery
      disease, (b) inflammatory disturbances of the microcirculation, (c) hypertensive
      microangiopathy, (d) rheologic abnormalities of the heart, and (e) pressure and
      volume overload due to hypertension and heart valve lesions (metabolic overload).

PMID- 1381798
TI  - Hypertension and vascular disease.
AB  - The use of antihypertensive drug treatment has altered the natural history of
      hypertension. Whereas congestive heart failure, cerebral hemorrhage, and renal
      failure were the major complications of untreated severe hypertension, myocardial
      infarction and thrombotic stroke have emerged as major problems in treated
      hypertensive patients. None of the major therapeutic trials in hypertension have
      provided evidence that reducing blood pressure reduces the risk of
      atherosclerotic complications of hypertension. Hypertension certainly aggravates
      the severity of atheromatous lesions in experimental animals, and may do so in
      humans. However, atherosclerosis is more closely related to disturbances in
      lipoprotein metabolism than to other factors. The common finding that serum
      cholesterol is raised in hypertensive patients may be due to atherosclerosis
      being the primary lesion, and hypertension a secondary complication rather than
      hypertension being the primary lesion.

PMID- 1381799
TI  - Diagnosis of left ventricular hypertrophy by echocardiography.
AB  - Left ventricular hypertrophy in systemic arterial hypertension is associated with
      an increased risk of morbidity and mortality due to cardiovascular disease.
      Therefore, the diagnosis of left ventricular hypertrophy is clinically important.
      In current clinical practice, echocardiography is the method of choice for
      diagnosing left ventricular hypertrophy. This review describes current,
      clinically applied techniques of measuring left ventricular mass using M-mode and
      two-dimensional echocardiography. Using M-mode techniques, left ventricular
      hypertrophy is usually present when myocardial mass estimates exceed 150 g/m2 in
      males and 120 g/m2 in females. Using two-dimensional echocardiography, upper
      limits of normal have been described to be slightly lower (102 g/m2 in males and
      88 g/m2 in females). In serial clinical two-dimensional echocardiographic
      studies, image acquisition and quantitation predominantly determine total
      variability in left ventricular mass estimates. Using any single technician and
      any single reader, left ventricular mass estimates in normal subjects may vary by
      35 g (standard deviation) between serial studies. Strategies to reduce the
      magnitude of this variability include increasing the number of technicians and
      readers acquiring and analyzing a single study.

PMID- 1381800
TI  - Studies of the heart using magnetic resonance.
AB  - Cardiovascular medicine is based on high-technology management of end-stage
      disease. Preventive medicine is preferable but, before magnetic resonance (MR),
      there was no noninvasive, safe, repeatable method of detecting occlusive vascular
      disease, which accounts for more deaths than any other disease at a
      presymptomatic stage. Demographic and animal studies show that occlusive vascular
      disease is not a normal aging process and is reversible. There was no method of
      monitoring the efficacy of preventive and therapeutic measures other than long,
      expensive, and sometimes inconclusive clinical trials. The rate of precession of
      atomic nuclei in a magnetic field is related to field strength. Creating a unique
      magnetic field in each volume of interest allows analysis of emitted radio
      signals to produce an image containing information about movement and local
      biochemical environments. MR produces accurate high resolution anatomical images
      and functional information including blood flow. It is already established as a
      method of choice in clinical cardiology for congenital heart disease and aortic
      disease. It is becoming established as a method of evaluating cardiovascular
      active drugs, and in the future MR will be used for diagnosis and as a population
      screening instrument for all cardiovascular disease including coronary artery
      disease.

PMID- 1381801
TI  - Prognostic significance of micrometastatic tumour cells in bone marrow of
      colorectal cancer patients.
AB  - Much of the information recorded at the time of surgery for malignant disease has
      been used, alone or in combination, to indicate the outlook for that patient,
      including probability of metastasis. However, direct evidence of tumour seeding
      in distant organs at that time is not available. An immunocytochemical assay for
      the epithelial cytokeratin protein (CK18) may fill this gap since it is a feature
      of epithelial cells but would not normally be in bone marrow. We looked for
      disseminated tumour cells preoperatively in bone marrow from 88 patients with
      radically resected colorectal carcinomas. Smears for 28 (32%) patients were
      positive for cells of epithelial origin, which were absent from aspirates taken
      from 102 controls with non-malignant disease. The prognostic value was assessed
      in a follow-up study with a median observation time of 35 (12-58) months.
      Patients who had bone marrow tumour cells in the aspirate showed a significantly
      shorter disease-free survival than those without tumour cells (p = 0.0084). In a
      Cox regression model multivariate analysis demonstrated that the finding of
      tumour cells in bone marrow is an independent, significant (p = 0.0035)
      determinant of relapse. Although the skeleton is not a preferred site of overt
      metastasis in colorectal cancer the demonstration of tumour cells in bone marrow
      has to be taken as evidence of the general disseminative capability of an
      individual tumour.

PMID- 1381802
TI  - Ganglioside-induced inhibition of in vivo immune response in mice.
AB  - In vitro immunomodulatory properties of gangliosides have been well characterized
      such as the ganglioside-induced modulation of CD4 on T lymphocytes and inhibition
      of lectin-induced proliferative response of lymphocytes. These findings have led
      to an interesting suggestion that gangliosides play a role as in vivo immune
      modulators, although this possibility is not clearly defined yet. We then first
      confirmed in vitro effects of gangliosides on murine immunocytes and examined in
      vivo effects of gangliosides on immune response in mice. Murine spleen cells that
      were treated with a ganglioside mixture (GS) purified from bovine brain exhibited
      a marked decrease in CD4 expression, while CD8 expression was slightly
      suppressed. Transplantation of GS-untreated control immunocytes that were
      isolated from syngeneic mice into the immune suppressed mice by X-ray irradiation
      restored in vivo immune responses, while GS-treated cells could not. Immune
      response was assayed by the evaluation of footpad swelling which was induced by
      immunization with sheep erythrocytes as antigens. Moreover, intramuscular
      administration of gangliosides into mice suppressed both immediate (Arthus)-type
      and delayed-type allergic reactions. These results suggest that gangliosides
      would be potential in vivo immune modulators.

PMID- 1381803
TI  - Site-specific antibodies to the DNA-binding domain of estrogen receptor
      distinguish this protein from the 3H-estradiol-binding protein in pancreas.
AB  - The estradiol-binding protein (EBP) in extracts of rat and rabbit pancreata was
      characterized by sucrose density gradient analysis, immunoaffinity adsorption and
      Western blot (immunoblot) analysis using polyclonal antibodies raised against
      EBP. Rat pancreatic extracts labeled with 3H-estradiol contained a readily
      resolvable peak of steroid-binding activity that sedimented as a 4S complex on
      sucrose density gradients in the presence or absence of 0.4 M KCl. Estrogen
      receptor (ER) from calf uterine cytosols sedimented as a 4S complex on gradients
      containing 0.4 M KCl and as an 8S entity on gradients without KCl. Incubation of
      cytosol fractions from rat pancreas and calf uterus with benzoyl-DL-arginyl-p
      nitroanilide (BAN) increased specific binding of 3H-estradiol to EBP but not to
      ER. Furthermore, two distinct site-specific antibodies to the DNA-binding domain
      of ER caused a marked increase in sedimentation rate of 3H-estradiol-labeled ER
      while normal rabbit serum and antibodies against EBP were ineffective in this
      regard. These data suggest that a significant portion, if not all, of the DNA
      binding domain of ER is absent from EBP. Examination of the amino acid sequence
      of the DNA-binding domain of ER revealed a region of 10 amino acids that is
      significantly homologous to somatostatin, a tetradecapeptide that is a co-ligand
      in the binding of 3H-estradiol to EBP. Based on this observation, a possible mode
      of action of EBP in pancreatic acinar cells is proposed.

PMID- 1381804
TI  - Induction of a humoral immune response to a Shiga toxin B subunit epitope
      expressed as a chimeric LamB protein in a Shigella flexneri live vaccine strain.
AB  - Shigella flexneri vaccine strain (SFL124) given orally, evokes humoral immune
      response in human volunteers. Such a strain, expressing antigenic epitope of B
      subunit of Shiga toxin, would also provide immunity to the toxin produced by some
      species of Shigella. A synthetic oligonucleotide, specifying an epitope [13-26
      amino acids (aa)] of the B subunit of Shiga toxin, was inserted into the lamB
      gene of Escherichia coli and expressed in the S. flexneri vaccine strain. The
      chimeric LamB protein functioned normally and the epitope was expressed at the
      surface of the bacteria. The animals immunized with the live bacteria, expressing
      the epitope or sonicated lysates, showed a humoral response that was specific to
      the peptide (13-26 aa) and to the whole B subunit molecule. The elicited antisera
      neutralized the toxin activity on HeLa cells up to 40%, while the purified IgG
      fractions from the sera gave 90% neutralization.

PMID- 1381805
TI  - Ultrastructural study on the adherence of Branhamella catarrhalis to
      oropharyngeal epithelial cell.
AB  - In the present study, it was observed that Branhamella catarrhalis adhere to the
      microplicae of the oropharyngeal epithelial cells. Both long and short
      microplicae patterns are present on the surface of oropharyngeal epithelial cells
      and the adherence ability of fimbriated Branhamella catarrhalis also varies
      according to the microplicae pattern. It was found that Branhamella catarrhalis
      attached more to one surface of the epithelial cell than to the other, suggesting
      that the presence of receptors are more on one surface than on the other.
      Branhamella catarrhalis did not attach to the mucus layer but directly to the
      epithelial cell surface. Ruthenium red staining specimen showed that Branhamella
      catarrhalis attached to a granular ruthenium red positive layer on the
      microplicae and also to a ruthenium red positive component, external to the unit
      membrane of the epithelial cell membrane.

PMID- 1381806
TI  - Serological cross-reaction between Yersinia enterocolitica O9 and non-O1 Vibrio
      cholerae bio-serogroup Hakata and antigenic analysis of their relationship by
      their lipopolysaccharides.
AB  - Cross-agglutination and cross-agglutinin absorption experiments were carried out
      on non-O1 Vibrio cholerae bio-serogroup Hakata (Hakata) and Yersinia
      enterocolitica O9 (O9). It was shown that the O-antigen of Hakata was closely
      related to that of O9 in an a, b-a, c type of relationship. The antigenic
      relationship between the O-antigens of the two bacteria was analyzed by passive
      hemolysis (PH) and passive hemolysis inhibition (PHI) tests by using their
      lipopolysaccharides (LPS) as antigen for sensitizing sheep red blood cells (SRBC)
      and, in the case of the latter, as an inhibitor in a PH system consisting of LPS
      coated SRBC, guinea-pig complement and anti-Hakata or O9 antiserum, both
      unabsorbed and absorbed with the heterologous Hakata or O9 antigen. In the PH
      experiment, unabsorbed anti-Hakata antiserum had hemolytic titers of 126,100 and
      2,600 against Hakata- and O9-LPS-coated SRBC, respectively, and anti-O9 antiserum
      had hemolytic titers of 19,400 and 38,800, respectively, against these SRBC. The
      PH experiment showed that anti-O9 antiserum contains a hemolysin reacting with
      the heterologous Hakata antigen at a high titer (19,400), while anti-Hakata
      antiserum contains a hemolysin reacting with the heterologous O9 antigen at a
      significant titer (2,600). The former was completely removed from anti-O9
      antiserum with the Hakata antigen and the latter from anti-Hakata antiserum with
      the O9 antigen. Thus, serological cross-reactivity was demonstrated between the
      Hakata and O9 strains.

PMID- 1381807
TI  - Prostate specific antigen.

PMID- 1381808
TI  - Prevalence of hepatitis C virus infections in dialysis patients and their
      contacts using a second generation enzymed-linked immunosorbent assay.
AB  - The prevalence of antibodies to the hepatitis C virus (HCV) was determined in 498
      hemodialysis patients from three german dialysis units, 121 staff members and 42
      family members using an enzyme-linked immunosorbent assay (ELISA) of the second
      generation which detects antibodies to a structural (C22) and to non-structural
      (C33c, C100, 5-1-1) recombinant antigens to HCV. Using the second generation
      ELISA 115 patients (23.1%) were anti-HCV positive versus 77 (15.5%) when sera
      were tested by an ELISA of the first generation containing only a non-structural
      antigen (C100). In 34 of these 40 discordant sera antibodies against at least one
      viral protein was found by a recombinant immunoblot assay. Of 5 sera containing
      antibodies to only one viral protein (C22) 3 were HCV RNA positive by polymerase
      chain reaction. Epidemiological evaluation of the patients revealed that the
      prevalence of anti-HCV was correlated to the duration of dialysis but not to the
      number of blood transfusions. Of 121 staff members 2 (1.6%) and 2 of 42 family
      members (4.7%) were positive indicating a low risk of the patients' contacts of
      acquiring HCV infection.

PMID- 1381809
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 40-1992. A 43-year-old Cambodian man with several years of
      recurrent bouts of fever and abdominal pain.

PMID- 1381810
TI  - Neural subsystems for object knowledge.
AB  - Critical issues in the cognitive neuroscience of language are whether there are
      multiple systems for the representation of meaning, perhaps organized by
      processing system (such as vision or language), and whether further subsystems
      are distinguishable within these larger ones. We describe here a patient (K.R.)
      with cerebral damage whose pattern of acquired deficits offers direct evidence
      for a major division between visually based and language-based higher-level
      representations, and for processing subsystems within language. K.R. could not
      name animals regardless of the type of presentation (auditory or visual), but had
      no difficulty naming other living things and objects. When asked to describe
      verbally the physical attributes of animals (for example, 'what colour is an
      elephant?'), she was strikingly impaired. Nevertheless, she could distinguish the
      correct physical attributes of animals when they were presented visually (she
      could distinguish animals that were correctly coloured from those that were not).
      Her knowledge of input stimulus. To explain this selective deficit, these data
      mandate the existence of two distinct representations of such properties in
      normal individuals, one visually based and one language-based. Furthermore, these
      data establish that knowledge of physical attributes is strictly segregated from
      knowledge of other properties in the language system.

PMID- 1381811
TI  - ATP receptor-mediated synaptic currents in the central nervous system.
AB  - Until now, the only well documented, fast excitatory neurotransmitter in the
      brain has been glutamate. Although there is evidence for adenosine 5'
      triphosphate (ATP) acting as a transmitter in the peripheral nervous system,
      suggestions for such a role in the central nervous system have so far not been
      supported by any direct evidence. Here we report the recording of evoked and
      miniature synaptic currents in the rat medial habenula. The fast rise time of the
      currents showed that they were mediated by a ligand-activated ion channel rather
      than a second messenger system, thus limiting the known transmitter candidates.
      Evidence was found for the presence on the cells of glutamate, gamma-aminobutyric
      acid, acetylcholine and ATP receptors, but not for 5-hydroxytryptamine (5HT3) or
      glycine receptors. The evoked currents were unaffected by blockers of glutamate,
      gamma-aminobutyric acid or acetylcholine receptors but were blocked by the ATP
      receptor-blocker, suramin and the desensitizing ATP receptor-agonist alpha,beta
      methylene-ATP. Our evidence identifies for the first time synaptic currents in
      the brain, mediated directly by ATP receptors.

PMID- 1381812
TI  - [Controversies concerning the pathogenesis and treatment of diabetic
      neuropathies].

PMID- 1381813
TI  - [The Aachen Aphasia Bedside Test--criteria for validity of psychologic tests].
AB  - The Aachen Aphasia Bedside Test (AABT) has been developed in order to examine
      aphasic patients within the first 4 to 6 weeks after onset of illness. The
      psychometric properties of the AABT were established by repeated examination of
      82 acute stroke patients, ratings by 20 raters on the basis of 10 videotapes,
      repeated examination of 28 chronic aphasics three times with an interval of 2
      days, and parallel examination of 47 chronic aphasic patients with the AABT and
      the Aachen Aphasia Test (AAT), administered on the same day. Objectivity,
      reliability and validity of the AABT were highly rated, indicating its usefulness
      in acute stroke cases. Data on the 82 acute stroke patients showed that an
      initial prognosis can be made as early as the fourth day after the stroke.

PMID- 1381814
TI  - Immunological characterization of the region of tau protein that is bound to
      Alzheimer paired helical filaments.
AB  - Tau protein is known to be present in the paired helical filaments (PHFs) of
      Alzheimer brains. This study investigated the fragments of tau protein that
      remain bound to pronase-treated PHFs and conditions that lead to the release of
      these tau fragments from the core structure of the PHF. Antibody 423 reacted with
      PHFs and with fetal rat tau but not with adult rat tau, pig tau, or recombinant
      human tau. Three other antibodies that react with the tubulin binding region of
      tau only reacted with PHFs after they were disrupted with formic acid or
      guanidine. Other antibodies that recognize tau sequences C terminal to the
      tubulin binding region also recognized pronase-treated PHFs. Antibodies SMI34 and
      T3P that recognize phosphorylated epitopes were reactive with pronase-treated
      PHFs. Tau fragments from the PHF were solubilized by acid or guanidine treatment.
      These findings suggest that the fragments of tau that are bound to PHFs and
      protected from pronase digestion include sequences from the tubulin binding
      region to the C terminus of tau. In addition, some of these sequences appear to
      be conformationally or post-translationally modified.

PMID- 1381815
TI  - Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged
      Fischer-344 rats.
AB  - Pergolide, a potent D2 presynaptic agonist with postsynaptic D2 agonist activity
      and some D1 agonist activity was administered in the diet (0.5 mg/kg/day) of male
      Fischer 344 rats from age 3 to age 26 months. We hypothesized that the potent D2
      presynaptic activity would reduce the baseline release of dopamine (DA) and
      thereby slow the formation of toxic oxidative metabolites that lead to age
      related deterioration of nigrostriatal DA neurons. Pair-fed rats served as
      controls. We observed age-related losses of fluorescent DA cell bodies in the
      substantia nigra pars compacta and of fluorescent DA terminals in the striatum;
      chronic pergolide administration prevented these losses. Pergolide administration
      also prevented the age-related diminution of DA fluorescence intensity in
      substantia nigra cell bodies. A large decline in 3H-DA uptake with age was
      partially prevented by pergolide administration. We found no age-related
      alteration in the concentration of DA in the striatum and pergolide did not alter
      this concentration. Pergolide treatment resulted in only minor alterations in
      striatal 3H-spiperone binding and no change in dendritic arborizations of either
      DA substantia nigra neurons or medium spiny striatal neurons. Pergolide
      administration also prevented an age-related decline in circulating FSH levels.
      The uptake data and quantitative morphological findings suggest that pergolide
      administration in the diet for 2 years exerts a protective effect on age-related
      deterioration of DA nigrostriatal neurons. This finding was consistent with
      clinical reports of a subset of patients with Parkinson's disease in whom long
      term efficacy of pergolide therapy is observed.

PMID- 1381816
TI  - The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in
      brain: evidence for the protective effect of chlormethiazole.
AB  - Studies were undertaken in mice and rats on the neurotoxic effects of
      methamphetamine on dopaminergic and 5-hydroxytryptaminergic neurones in the brain
      and the neuroprotective action of chlormethiazole. In initial studies, mice were
      injected with methamphetamine (5 mg/kg, i.p.) at 2 hr intervals, to a total of 4
      times. This procedure produced a 66% loss of striatal dopamine and a 50% loss of
      tyrosine hydroxylase activity 3 days later. Chlormethiazole (50 mg/kg, i.p.),
      given 15 min before each dose of methamphetamine, totally prevented the
      methamphetamine-induced loss of tyrosine hydroxylase activity and partly
      prevented the loss of dopamine. Phencyclidine (20 mg/kg, i.p.), given in place of
      chlormethiazole, also prevented the loss of tyrosine hydroxylase. Administration
      to rats of 4 doses of methamphetamine (15 mg/kg, i.p.) at 3 hr intervals resulted
      in a 75% loss of striatal dopamine 3 days later and a similar loss of 5-HT and 5
      HIAA in cortex and hippocampus. Chlormethiazole (50 mg/kg, i.p.), given 15 min
      before each injection of methamphetamine, protected against the loss of dopamine
      and indoleamine content, in the respective regions. Pentobarbital (25 mg/kg,
      i.p.) also provided substantial protection but diazepam (2.5 mg/kg, i.p.) was
      without effect. Confirming earlier studies, dizocilpine (1 mg/kg) also provided
      substantial protection against the methamphetamine-induced neurotoxicity.
      Preliminary data indicated that chlormethiazole was not neuroprotective because
      of a hypothermic action. These data therefore demonstrate that chlormethiazole is
      an effective neuroprotective agent against methamphetamine-induced neurotoxicity
      and extend the evidence for the possible value of this drug in preventing
      neurodegeneration.

PMID- 1381817
TI  - Effects of short- and long-term administration of fluoxetine on the monoamine
      content of rat brain.
AB  - The effects of repeated doses of fluoxetine over time and dose-responses of the
      content of indoles and catecholamines and metabolism, were examined in rats in
      relation to the concentrations of the parent compound and its active metabolite
      norfluoxetine in brain. Brains were removed for assays of the regional content of
      monoamines and concentrations of drugs 24 hr after the last dose on days 1, 7 and
      21 of a twice-daily schedule of fluoxetine (15 mg/kg, i.p.). Measurements were
      also taken 1 week after the last dose (7.5 and 15 mg/kg, b.i.d.) of the 21-day
      regimen. On day 1 fluoxetine did not change the content of serotonin (5-HT) but
      reduced the concentrations of 5-hydroxyindolacetic acid (5-HIAA) in the
      hippocampus and cortex, compatible with the action of a blocker of the uptake of
      5-HT. Continued injections of fluoxetine, however, significantly reduced 5-HT in
      the brain of the rat, the depletion being significant on days 7 and 21 in the
      hippocampus and cortex, respectively. The content of indoles remained
      significantly decreased for at least a week after the last dose of fluoxetine in
      the 21-day regimen, although the concentrations of 5-HIAA (but not 5-HT) totally
      recovered at the smaller dose (7.5 mg/kg) in all regions of the brain (cortex,
      hippocampus and striatum). In spite of slight changes in the concentrations and
      metabolism of dopamine (DA) in the striatum, 24 hr after the last dose (15
      mg/kg), treatment with drug had no significant long-term effects on the content
      of catecholamines in these regions of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381818
TI  - Detection of activated platelets using activation-dependent monoclonal antibody
      (SZ-51) in clinical disorders.
AB  - Platelets may become activated in a number of clinical disorders and participate
      in thrombus formation. A direct test for activated platelets in whole blood has
      been developed by radioimmunoassay with 125I labelled SZ-51, an antibody specific
      for an alpha-granule membrane protein (GMP-140) that associates with the platelet
      surface during secretion. The assay with sufficient sensitivity can be applied
      satisfactorily to detect as few as 2% activated platelets. In 50 normal subjects,
      minimal GMP-140 molecules per platelet were expressed on the surface of
      circulating platelets. The expression of GMP-140 molecules was increased
      transiently in 10 patients undergoing cardiopulmonary bypass, especially at the
      end of bypass. Evaluation of 18 patients with epidemic hemorrhagic fever (EHF)
      showed that the number of GMP-140 molecules on the platelet surface increased
      significantly, particularly at the shock phase, and closely related to the four
      different phases of EHF. In 9 patients suffered from acute myocardial infarction
      (AMI), the number of GMP-140 molecules changed with the procession of AMI and the
      highest occurred at the 48th h after AMI. The GMP-140 molecules were also
      increased in patients with asthma attack (n = 14), but not in patients with
      idiopathic thrombocytopenic purpura (n = 11). Considered together, these results
      suggest that activated platelets can be measured reliably in whole blood using
      radiolabeled SZ-51 antibody and the detection of activated platelets is
      potentially useful in identifying patients with certain thrombotic disorders.

PMID- 1381819
TI  - Platelets and vitronectin: immunocytochemical localization and platelet
      interaction with exogenously added vitronectin.
AB  - Vitronectin stores were localized in human platelets by immunofluorescence,
      confocal laser microscopy, and immunoelectron microscopy. In ultrathin
      cryosections, the immunogold labelling was mainly observed in the alpha-granules,
      although occasional immunolabelling of the platelet surface was present. The
      interaction between thrombin-stimulated platelets and exogenously added
      vitronectin was also explored. This vitronectin had been purified by heparin
      affinity chromatography. Binding of vitronectin to thrombin-stimulated platelets
      was demonstrated by flow cytometry. The immunoelectron microscopical studies
      revealed that this binding was mainly restricted to clumps of released alpha
      granular material on the platelet surface. The possible significance of the
      interaction between exogenous vitronectin and released platelet proteins is
      discussed.

PMID- 1381820
TI  - Nurses' perceptions of the dimensions of nursing care episodes.
AB  - The purpose of this exploratory study was to describe the dimensions of 17
      nursing care episodes as perceived by nurses. The episodes represented recurrent
      nursing care situations in the postoperative period. Nineteen nurses judged the
      dissimilarity of all possible pairs of the episodes. An additional 14 nurses
      rated each episode on 10 attribute scales. Multidimensional scaling (MDS), was
      used to analyze nurses' dissimilarity judgments. A three-dimensional MDS
      configuration, which accounted for 51% of the variance of nurses' optimally
      scaled data, was chosen to describe the structure of the episodes. To interpret
      the dimensions of the MDS configuration objectively, multiple regression was used
      to correlate the attributes, one at a time, with the coordinates of the episodes
      in the configuration. The dimensions of the MDS configuration were interpreted as
      (a) the degree of independence patients could achieve in the episodes, (b) the
      nursing knowledge or skill needed in the episodes, and (c) the degree to which
      nurses could individualize the episodes for patients. Information obtained from
      the MDS analysis can be used to help nurses (a) explicitly evaluate and
      communicate their expectations for patients regarding activities to promote
      independence and (b) better articulate the specialized knowledge and skills
      needed to provide nursing care.

PMID- 1381822
TI  - [Long-term mexiletine treatment of ventricular arrhythmia in patients after
      myocardial infarction].
AB  - Eighty two patients with ventricular extrasystole (VES) after myocardial
      infarction had been treated with antiarrhythmic drugs in the half (41 patients)
      with mexiletine (M) and in the half (41 patients) with other ones. The mortality
      rate in the M-group was twice time lower than in the other, however this
      difference was statistically not significant. M was mostly effective in VES of
      III and IVb degree after Lown's classification and did not cause any
      deterioration of the left ventricle function.

PMID- 1381821
TI  - [Early results of the treatment of Hodgkin's disease in adults using the seven
      drug cytostatic protocol].
AB  - 65 adult patients with Hodgkin's disease were treated acc. to multidrug protocol
      proposed by I. Koza et al. including doxorubicin, vincristine, vinblastine,
      bleomycin, procarbazine, lomustine and prednisone. 4 drugs (3 cytostatics and
      prednisone) including cycles were given repeatedly every 4 weeks. In the group of
      first line therapy (39 persons) 61.5% CR and 23% PR was obtained i.e. 84.5%
      therapeutic responses. The protocol used as salvage therapy resulted in 30% CR
      and 23% PR. Undesirable gastrointestinal effects were observed less commonly than
      after ABVD and CVPP schemes but myelosuppressive effect was more often seen and
      required attenuation of cytostatic drugs doses in the further cycles of therapy.
      The considered protocol seems to be a valuable one approaching to -but not
      achieving- the results of MOPP and ABVD schemes: is better tolerated because of
      elimination of strong emetic cytostatics (chlormethine and decarbazine) but late
      toxicity could be evaluable only after several years.

PMID- 1381823
TI  - [Effect of epirubicin on the heart conduction system in patients with Hodgkin's
      disease].
AB  - 24 patients (12 women and 12 men) aged 17 to 70 years with Hodgkin's disease in
      the clinical stages IIA-IVB were treated according to the polychemotherapeutic
      schemes containing epirubicin (epiDX). Using the 24-hour ambulatory ECC on the
      day before and the day of drug application as well as after completion of the
      therapy, heart rate, arrhythmias and conduction abnormalities were estimated.
      There was statistically insignificant decrease in heart rate (mean, minimal and
      maximal) on the day of epiDX administration and after therapy completion.
      Arrhythmias in form of supraventricular and ventricular extrasystoles including
      bigeminy and couplets of VES in one patient and two episodes of atrial
      tachycardia in another one on the day of drug injection were noticed. In 2 young
      women occurred interruption of sinus rhythm lasting longer than 3 sec., due to
      sinus arrest in one and due to 2:1 sinus exit block in the second one. The above
      mentioned disturbances were in majority of patients not associated with clinical
      symptoms. The authors conclude that the reduction in heart rate and SVES
      formation might be in the majority of patients neurogenic but in some of them as
      well as VES generation result from epiDX action.

PMID- 1381824
TI  - [Prospects in the treatment of AIDS. I. Research trends].

PMID- 1381825
TI  - [Prospects in the treatment of AIDS. II. AZT and related compounds; practical
      conclusions].

PMID- 1381826
TI  - Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria
      terminalis project to the midbrain central gray in the rat.
AB  - The central nucleus of the amygdala, bed nucleus of the stria terminalis, and
      central gray are important components of the neural circuitry responsible for
      autonomic and behavioral responses to threatening or stressful stimuli. Neurons
      of the amygdala and bed nucleus of the stria terminalis that project to the
      midbrain central gray were tested for the presence of peptide immunoreactivity.
      To accomplish this aim, a combined immunohistochemical and retrograde tracing
      technique was used. Maximal retrograde labeling was observed in the amygdala and
      bed nucleus of the stria terminalis after injections of retrograde tracer into
      the caudal ventrolateral midbrain central gray. The majority of the retrogradely
      labeled neurons in the amygdala were located in the medial central nucleus,
      although many neurons were also observed in the lateral subdivision of the
      central nucleus. Most of the retrogradely labeled neurons in the BST were located
      in the ventral and posterior lateral subdivisions, although cells were also
      observed in most other subdivisions. Retrogradely labeled neurotensin,
      corticotropin releasing factor (CRF), and somatostatin neurons were mainly
      observed in the lateral central nucleus and the dorsal lateral BST. Retrogradely
      labeled substance P-immunoreactive cells were found in the medial central nucleus
      and the posterior and ventral lateral BST. Enkephalin-immunoreactive retrogradely
      labeled cells were not observed in the amygdala or bed nucleus of the stria
      terminalis. A few cells in the hypothalamus (paraventricular and lateral
      hypothalamic nuclei) that project to the central gray also contained CRF and
      neurotensin immunoreactivity. The results suggest the amygdala and the bed
      nucleus of the stria terminalis are a major forebrain source of CRF, neurotensin,
      somatostatin, and substance P terminals in the midbrain central gray.

PMID- 1381827
TI  - Masculinization of growth hormone (GH) secretory pattern by dihydrotestosterone
      is associated with augmentation of hypothalamic somatostatin and GH-releasing
      hormone mRNA levels in ovariectomized adult rats.
AB  - The role of androgen in the sexual dimorphism in hypothalamic growth hormone (GH)
      releasing hormone (GHRH) and somatostatin (SS) gene expression was examined in
      rats. In the first study, the SS and GHRH mRNA levels were measured in both male
      and female rats at 4, 6, 8, and 10 weeks of age. A significant sex-related
      difference in the SS and GHRH mRNA levels was observed after 8 weeks of age, when
      sexual maturation is fully attained. Male rats had higher SS and GHRH mRNA levels
      than the female rats. In the second study, adult ovariectomized rats received
      daily injection of dihydrotestosterone (DHT), nonaromatizable testosterone, at a
      dose of 2 mg/rat for 21 days. The DHT treatment masculinized the GH secretory
      pattern, which was indistinguishable from that of intact male rats, and
      simultaneously augmented the SS and GHRH mRNA levels. The DHT treatment of
      ovariectomized rats after hypophysectomy significantly raised the level of SS
      mRNA, but not that of GHRH mRNA compared to the control animals. These findings
      suggest that the activation of the SS gene expression through androgen receptor
      plays an important role in the maintenance of sexual dimorphism in GH secretion
      in rats.

PMID- 1381829
TI  - Morphological evidence for a substance P projection from medial septum to
      hippocampus.
AB  - The medial septal nucleus provides one of the major afferents to the hippocampal
      formation. The two major types of neurons present in the medial septum are
      cholinergic and GABAergic, but other types of neurons are also present. A small
      population of substance P-containing neurons is present along the border between
      the medial and lateral septum, but it is unclear whether these project to the
      hippocampus. The present study, by employing both anterograde and retrograde
      tracing techniques, combined with immunocytochemistry for substance P, provides
      direct morphological evidence for a substance P projection from the lateral
      region of medial septum to a portion of CA2/3a, which is restricted to the mid
      septotemporal portion of the hippocampus.

PMID- 1381828
TI  - Galanin inhibits rat pancreatic amylase release via cholinergic suppression.
AB  - The effects of galanin on pancreatic exocrine function were examined using rat
      pancreatic tissues. In anesthetized rats, galanin (40 micrograms/kg/h) decreased
      amylase secretion stimulated by 2-deoxy glucose (5.8 +/- 0.1 vs. 3.1 +/- 0.1
      times basal) and cholecystokinin octapeptide (21.5 +/- 0.6 vs. 16.8 +/- 0.5),
      while not inhibiting bethanechol-stimulated secretion. In dispersed acini, there
      was no effect of galanin alone (10(-8) to 10(-13) M) on amylase release, nor did
      galanin (10(-6) or 10(-8) M) coincubation affect amylase release stimulated by
      bethanechol (10(-3) to 10(-7) M) or CCK-8 (10(-8) to 10(-13) M). Using pancreatic
      lobules, coincubation with galanin (10(-6) M) suppressed 75 mM KCl-stimulated
      amylase secretion and ACh release (10.1 +/- 0.6% vs. 7.3 +/- 0.4%). Veratridine
      stimulated (10(-4) M) amylase secretion and ACh release (12.4 +/- 1.7% vs. 8.5 +/
      0.7%) were similarly diminished.

PMID- 1381830
TI  - Distribution and effects of neuropeptide Y, vasoactive intestinal peptide,
      substance P, and calcitonin gene-related peptide in human middle meningeal
      arteries: comparison with cerebral and temporal arteries.
AB  - A sparse to moderate supply of nerve fibers containing neuropeptide Y-like
      immunoreactivity (NPY-LI), vasoactive intestinal polypeptide (VIP-LI), substance
      P (SP-LI), and calcitonin gene-related peptide (CGRP-LI) was demonstrated in the
      walls of human middle meningeal arteries. Comparison with similar studies on
      human cerebral and temporal arteries indicated a similar distribution and
      density. The immunoreactive material in all three arterial regions was
      characterized by reversed-phase high pressure liquid chromatography (HPLC) and
      radioimmunoassay (RIA). The major peak of NPY-LI, VIP-LI, SP-LI, and CGRP-LI in
      each extract eluted approximately with the same elution volume as that of the
      corresponding synthetic analogues. The concentration of NPY in the middle
      meningeal arteries was lower as compared to the temporal arteries. Low
      concentrations of SP-LI and CGRP-LI were found in the middle meningeal arteries
      as compared to the cerebral arteries. In isolated ring segments of human middle
      meningeal and cerebral arteries, NPY caused vasoconstriction but did not
      potentiate the contractile response of noradrenaline. In the temporal artery, NPY
      did not induce contraction but potentiated the vasoconstrictor response to
      noradrenaline. Vasoactive intestinal polypeptide, peptide histidine methionine
      27, SP, neurokinin A, and CGRP relaxed all three types of cephalic arteries. The
      peptide effects were not antagonized by propranolol, atropine, or cimetidine.
      Comparison of the responses to VIP and SP of vessels from the different regions
      showed a similar pattern of reactivity. The response to SP was slightly (p less
      than 0.05) more potent, whereas the responses to CGRP were less potent in the
      middle meningeal as compared to that in cerebral (p less than 0.005) vessels.

PMID- 1381831
TI  - Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity
      in rats.
AB  - Neuropeptide Y (NPY) is a powerful appetite stimulant, and hypothalamic
      concentrations rise after food deprivation and in experimental diabetes.
      Serotonergic drugs such as dexfenfluramine are inhibitors of feeding. We measured
      hyothalamic NPY and NPY mRNA, along with galanin, neurotensin, and somatostatin
      in chow-fed rats and in rats with dietary obesity, and examined the effect of
      dexfenfluramine on these peptides in this model. Sixty-five rats were fed a
      palatable diet (condensed milk, sucrose and chow) for 6 weeks, which produced
      significant weight gain compared to twenty fed standard chow (145.1 +/- 2.3 g vs.
      113.4 +/- 3.2 g, p less than 0.001). Groups of animals were treated for 7 days or
      28 days with dexfenfluramine (1.8 mg/kg/day) or saline intraperitoneally via
      miniosmotic pumps. Hypothalami were dissected into medial and lateral blocks, and
      NPY, galanin, neurotensin, and somatostatin were measured by radioimmunoassay.
      Neuropeptide Y mRNA was measured by Northern blotting. Hypothalamic NPY was
      significantly higher in the palatable diet group compared to chow-fed controls
      (medial hypothalamus: 86.6 +/- 7.6 vs. 65.7 +/- 4.0 pmol/g tissue, p less than
      0.02, lateral hypothalamus 71.2 +/- 6.6 vs. 53.1 +/- 3.6 pmol/g tissue, p less
      than 0.05), but NPY mRNA was unchanged. Although dexfenfluramine was effective at
      reducing weight gain in the animals fed the palatable diet, this did not result
      in any changes in the hypothalamic neuropeptides measured. Neuropeptide Y may be
      of importance in diet-induced obesity but the weight loss produced by
      dexfenfluramine in such animals is not mediated by changes in hypothalamic NPY.

PMID- 1381832
TI  - Characterization of porcine gastric galanin.
AB  - The presence of a peptide capable of producing powerful contractions of rat small
      intestinal smooth muscle was detected in chromatographic fractions derived from
      porcine gastric corpus extracts. The pharmacological characteristics of this
      entity suggested that it might be galanin and on its purification to homogeneity,
      amino acid composition and sequence analysis demonstrated the identify of the
      gastric and intestinal forms of galanin. The presence of galanin in the gastric
      corpus tissue and its ability to affect gastric smooth muscle activity, gastrin
      release, and gastric acid secretion suggest potential important physiological
      roles for galanin in the stomach.

PMID- 1381833
TI  - Effects of an interferon inducer bropirimine on bleomycin-induced lung fibrosis
      in hamsters.
AB  - The antifibrotic effect of an interferon inducer, bropirimine (2-amino-5-bromo-6
      phenyl-4(3H)-pyrimidinone, ABPP) was evaluated in bleomycin (BLM)-hamster model
      of lung fibrosis. ABPP is an orally active biological response modifier and has
      immunomodulatory, antiviral, and antineoplastic activities. The hamsters were
      randomized in four groups and treated with either bropirimine (100 mg/kg,
      intraperitoneally) suspended in carboxymethylcellulose (CMC, 10 mg/10 mg/ml) or
      CMC alone each day for sixteen days. After two days, the hamsters received either
      single bolus of BLM (7.5 U/5 ml/kg) or an equivalent volume of saline by the
      transoral endotracheal route. Groupings were assigned as: CMC + saline (CS), ABPP
      + saline (AS), CMC + BLM (CB) and ABPP + BLM (AB). Animals were sacrificed at
      fourteen days after intratracheal installation of either BLM or saline. Their
      lungs were lavaged and processed for morphometric and biochemical studies. ABPP
      had little effect in preventing BLM-induced weight loss and lung injury. ABPP was
      found to reduce the BLM-induced accumulation of collagen in the lung as measured
      by hydroxyproline content. The hamsters in AB group had significantly less
      collagen than the hamsters in CB group: 995 and 1157 micrograms
      hydroxyproline/lung, respectively. Administration of ABPP prevented the BLM
      induced increase in the lung prolyl hydroxylase activity. The total number of
      monocytes and eosinophils recovered from the bronchoalveolar lavage fluid (BALF)
      of the AB group were significantly lower than that of the animals in CB group.
      However, the BALF supernatant protein content from animals in AB group (7.9
      mg/lung) was significantly higher than that of CB group (4.5 mg/lung).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1381834
TI  - Rod opsin cDNA sequence from the sand goby (Pomatoschistus minutus) compared with
      those of other vertebrates.
AB  - The absorbance spectra of rods from the sand goby were measured by using
      microspectrophotometry. Analysis of the averaged spectra shows that the rod
      visual pigment has a maximum absorbance (lambda max) at approximately 501 nm. A
      sand goby retinal cDNA library was constructed and then screened with a partial
      sand goby rod opsin clone obtained by the polymerase chain reaction (PCR). The
      screening of the library yielded a full length rod opsin clone. The cDNA sequence
      and deduced amino acid sequence of this clone are compared with those of other
      vertebrate rod opsins.

PMID- 1381835
TI  - Cloning of ShIII (Shaw-like) cDNAs encoding a novel high-voltage-activating, TEA
      sensitive, type-A K+ channel.
AB  - Transient voltage-dependent potassium (K+) currents, also known as A currents,
      have been of great interest to neurophysiologists due to their special roles in
      neuronal excitability. Several cDNAs encoding transcripts expressing A currents
      have been characterized. Recently, a cDNA (KShIIIC or Raw3) was isolated which
      expresses an unusual A current that is highly sensitive to TEA, and activates at
      potentials more positive than -20 mV. Channels containing this protein may have
      specialized roles in modulating the electrical behaviour of neurons. Here we
      report the isolation and characterization of two rat cDNAs corresponding to two
      alternatively spliced transcripts (KShIIID.1 and KShIIID.2) from another gene
      (KShIIID) of the same subfamily as KShIIIC, the ShIII or Shaw-related gene
      subfamily. KShIIID.1 also expresses an unusual high-voltage-activating, TEA
      sensitive A-type channel. There are, however, significant differences between
      KShIIIC and KShIIID channels which may have interesting functional consequences.
      The two most important differences are: (i) KShIIID channels conduct in the
      steady-state over a much broader window of potentials than KShIIIC; this reflects
      differences between the kinetic schemes of the two channels; and (ii) KShIIID
      inactivates with significantly slower kinetics than KShIIIC. The identification
      of KShIIID transcripts contributes to our knowledge of the molecular components
      that may determine the functional diversity of A currents and provides exciting
      opportunities to increase our understanding of the structure and function of K+
      channels.

PMID- 1381836
TI  - Protection by a new synthetic protease inhibitor, ONO3307, of the rat exocrine
      pancreas during acute edematous pancreatitis induced by a supramaximal dose of
      caerulein in comparison with FOY007.
AB  - The present study investigated the protective effects of the new potent synthetic
      protease inhibitors, ONO3307 (4-sulfamoyl phenyl-4-guanidinobenzoate
      methanesulfonate) and FOY007 (gabexate misilate), on the exocrine pancreas in rat
      caerulein-induced acute pancreatitis in both in vitro and in vivo experiments.
      These protease inhibitors prevented hyperamylasemia, pancreatic edema, congestion
      of amylase, redistribution of lysosomal enzyme in acinar cells, and lactic
      dehydrogenase (LDH) discharge from dispersed acini. They also inhibited the
      cathepsin B leakage from the lysosomes in a dose-dependent manner in doses of 2
      10 mg/kg.h of ONO3307 and 20-50 mg/kg.h of FOY007. These results indicate that
      both ONO3307 and FOY007 exert protective effects against pancreatitis at
      subcellular levels in lysosomes and cellular or organelle membranes. Proteases
      appear to be important in the pathogenesis and development of acute pancreatitis,
      and low-molecular-weight protease inhibitors may be of clinical use in the
      treatment of acute pancreatitis.

PMID- 1381837
TI  - Voltage-dependent calcium current and the effects of adrenergic modulation in rat
      aortic smooth muscle cells.
AB  - Smooth muscle cells from rat aorta were cultured in defined, serum-free medium
      and studied using whole-cell patch-clamp techniques. Under conditions designed to
      isolate currents through Ca channels, step depolarizations produced inward
      currents which were fast in onset and inactivated rapidly, with little sustained
      inward current being observed. Both Ni and Cd blocked these currents, with Ni
      being effective at 50 microM. Removal of external Na or addition of 1 microM
      tetrodotoxin had no effect. Peak inward currents were attained at about -15 mV,
      with half-maximal activation at -41 mV using -80 mV holding potentials. The
      transient inward currents were reduced by depolarized holding potentials, with
      half-maximal steady-state inactivation at -48 mV. In three of the 98 cells
      studied, small maintained inward currents were observed with a -40 mV holding
      potential. The Ca channel antagonist nicardipine (5 microM) blocked the transient
      inward current while neither of the dihydropyridine Ca channel agonists S(+)202
      791 and (-)BAY K 8644 produced a significant augmentation of sustained inward
      current. At 10 microM, both noradrenaline and adrenaline but not phenylephrine
      decreased the peak inward current. This inhibition was unaffected by a variety of
      adrenoceptor antagonists and was also observed when internal solutions having
      high Ca buffering capacity were used, but was absent when GDP-beta-S instead of
      GTP was included in the pipette solution. The main conclusions from this study
      are that under our cell culture conditions, rat aortic smooth muscle cells
      possess predominantly a transient, low-threshold-activated inward Ca current and
      that this Ca current is inhibited by certain adrenoceptor agonists but with a
      quite atypical adrenoceptor antagonist pharmacology.

PMID- 1381838
TI  - Housing influences exploration and social interaction of control and DSP-4
      treated rats.
AB  - Exploratory behavior and social interaction were investigated in rats that were
      reared in different social environments following neonatal injection with either
      water vehicle or the norepinephrine neurotoxin, DSP-4. At weaning, they were
      placed in a familiar or novel bedding type and were housed in either vehicle
      control-only, DSP-4-only, or mixed vehicle control and DSP-4 groups for 10 days.
      They were then observed in three different situations: the home cage, the cage of
      an unfamiliar rat, and an open field. Compared to rats housed in vehicle control
      only or DSP-4-only groups, rats housed in mixed DSP-4 and vehicle control groups
      showed elevated exploration behavior in the home cage. Also, rats housed in mixed
      groups in the familiar bedding, but not the novel one, showed abnormally low
      levels of rearing in an open field test and reduced social interaction with
      unfamiliar rats. The implications of these results for a new animal model of
      anxiety are discussed.

PMID- 1381839
TI  - Incidental finding of rectal carcinoma during transrectal US for prostatic
      diseases.
AB  - During transrectal ultrasound (TRUS), rectal carcinoma was an incidental finding
      in seven patients among a series of 5,000 TRUS examinations. TRUS was performed
      in seven patients with symptoms characteristic of prostatic diseases. All seven
      patients underwent examination by at least one physician before TRUS and, except
      for abnormal prostatic findings, no tumors were detected during digital rectal
      examination (DRE). The tumors were clearly visualized with TRUS and were easily
      palpated during DREs performed after TRUS. They were large and were located
      mainly along the posterior and lateral walls of the rectum. All the tumors were
      diagnosed by means of proctoscopy; the biopsy findings were positive, and the
      pathologic staging indicated advanced disease: adenocarcinoma of the rectum with
      a minimum grade of Dukes C. It is recommended that, in addition to evaluation of
      scans obtained in the transverse plane, the multiplane transducer be used to
      evaluate the longitudinal plane of the rectum for detection of possible
      undiscovered tumors.

PMID- 1381840
TI  - [Epilepsy and thyrotoxicosis in a 4-year-old boy].
AB  - Hyperthyroidism in childhood has a relative incidence of 5%. The presence of
      epilepsy secondary to thyrotoxicosis is very unusual. We report the case of a
      four-year old boy with thyrotoxicosis due to Graves' disease. This patient
      developed a generalized tonic-clonic seizure followed by left sided partial motor
      status epilepticus. The EEG was markedly abnormal. The EEG was normal after five
      months of the ablative therapy. At the present time the patient is seizure-free
      without any antiepileptic medication and receiving replacement therapy with
      thyroxin due to post-ablation hypothyroidism. We conclude that this is the first
      reported case with this association in our country. We discuss the possible
      pathophysiological mechanism involved in the development of seizures in this
      patient.

PMID- 1381841
TI  - Prostatic heat treatments.

PMID- 1381842
TI  - [The little Dagoberts of Saint-Eloi].

PMID- 1381843
TI  - [When the music begins!].

PMID- 1381844
TI  - Amplification of dengue 2 virus ribonucleic acid sequence using the polymerase
      chain reaction.
AB  - The polymerase chain reaction (PCR) has been adapted to the amplification of
      dengue type 2 virus (DEN2) nucleic acid sequences. A pair of 20-mer
      oligonucleotides were designed and synthesized based on conserved sequence blocks
      of DEN2 strains isolated from different geographical areas. RNA samples were
      prepared from two DEN2 strains, prototype New Guinea C (NGC) and local isolate
      Hainan 98 (HN98). The reverse transcription step was performed for cDNA synthesis
      before the standard PCR procedures. The amplified products were fragments about
      476 bp in length, corresponding to the upper one third of DEN2 envelope gene (E1
      to E476 nt). Specificity of the amplification products was confirmed by "nested"
      PCR using the internal primers and by Southern and dot blot hybridization to
      cloned DEN2 cDNA probes following agarose gel electrophoresis. Further
      improvement and the potential application of the methods in study of dengue virus
      RNA are discussed.

PMID- 1381845
TI  - Serological and virological studies of Japanese encephalitis in the Terai region
      of Nepal.
AB  - In 1987 and 1990, serum samples were collected from people living in the two
      districts (Itahari and Chitwan) of the Terai region of Nepal. Antibodies against
      Japanese encephalitis (JE) virus in these sera were detected by the
      hemagglutination inhibition (HI) and neutralization (N) tests. By the HI test, 26
      out of 172 (15.1%) sera from Chitwan and 15 out of 137 (10.9%) sera from Itahari
      showed positive titers. Higher positive rates were shown by the N test, where 46
      out of 172 (26.7%) sera from Chitwan and 22 out of 137 (16.1%) sera from Itahari
      had antibodies against JE virus. A JE strain was isolated from a blood specimen
      of a pig raised in Kathmandu. When the nucleotide sequence of the pre-M region of
      the strain was compared to the same region of the other JE virus strains
      reported, the highest similarity was observed to the strains isolated in Nepal in
      1985. These results suggest that the Terai region has been an epidemic area of
      JE.

PMID- 1381846
TI  - Studies on common antigenicities between the Belo Horizonte strain, Brazil of
      Schistosoma mansoni eggs and Biomphalaria snails by immunoelectrophoresis.
AB  - Immunoelectrophoretic studies of common antigenicities were carried out by using
      rabbit sera immunized against the Belo Horizonte strain of Schistosoma mansoni
      eggs and crude antigens of Biomphalaria snails and vice versa. With regard to
      common antigenicities between S. mansoni eggs and Biomphalaria snails, S. mansoni
      eggs produced 4 to 5 bands with Biomphalaria glabrata pigmentado, 3 to 4 bands
      with B. glabrata albino and only 1 band with B. straminea. In our laboratory, the
      infection rate of S. mansoni miracidia to B. glabrata pigmentado was 64.3% and
      55.0% for B. glabrata albino, but B. straminea was not found to be susceptible to
      S. mansoni miracidia. It was observe that more bands were seen between S. mansoni
      egg and suitable hosts. Biomphalaria snail crude antigens were fractionated by
      Sephadex G-100 column, and each fraction antigen was tested with anti-S. mansoni
      egg sera by immunoelectrophoresis. As results, three fractions were collected
      form each snail strains. The common antigenicities between fractionated antigens
      from Biomphalaria snails crude antigens and anti-S. mansoni egg sera mostly
      existed in the first fraction and they were estimated to have molecular weights
      over 45,000.

PMID- 1381847
TI  - [Gamma delta T cells and collagen disease].

PMID- 1381848
TI  - [The role of serotonin, histamine and the kallikrein-kinin system in the
      pathogenesis of asphyxic attacks in bronchial asthma].
AB  - Altogether 300 patients suffering from bronchial asthma were examined for
      serotonin metabolism, the kallikrein-kinin system and histamine. A study was also
      made of the information relations of the indicated parameters to diverse groups
      of the signs using Shannon's technique. It has been revealed that serotonin and
      the kallikrein-kinin system are of importance in the pathogenesis of changes in
      the efficacy of the diffusion lung capacity in severe bronchial asthma. The
      authors discuss the significance of excessive accumulation of serotonin and
      bradykinin as a marker of the impairment of endothelial function of pulmonary
      vessels, specified by the damaging action of free radicals and immune complex
      allergic vasculitis as well. Histamine along with macrophages act as delimiters
      of allergic inflammation, with their action being mediated by negative feedback.

PMID- 1381849
TI  - Heparin cofactor II deficiency in the elderly: comparison with antithrombin III.
AB  - We investigated heparin cofactor II (HC II) levels and their relationship to
      other haemostatic factors in the elderly in comparison with antithrombin III (AT
      III). We measured plasma HC II activity levels in 166 subjects aged from 61 to 99
      years using a chromogenic method. HC II levels (94.4 +/- 18.5%) in the healthy
      elderly subjects were significantly (p less than 0.001) lower than in 40 healthy
      adult controls under 60 years of age (mean age: 51.5 years; 111.6 +/- 21.2%). HC
      II levels in the elderly subjects decreased further with age (r = 0.308, p less
      than 0.001) and the extent of the decrease was more marked than that for AT III
      (r = 0.179, p less than 0.05). There was no significant sex difference in HC II
      levels in the elderly. HC II levels correlated significantly with AT III levels
      and with acute phase reactants including sialic acid, fibrinogen, and PAI-1. HC
      II levels also correlated with factor VII, plasminogen, alpha 2-plasmin
      inhibitor, serum lipid, pseudocholinesterase, and albumin levels. These
      correlations were also found for AT III except active PAI-1 and tPA-PAI-1
      complexes, but the correlations with acute phase reactants were stronger for HC
      II than AT III. We divided 154 elderly subjects into 4 groups by their
      pseudocholinesterase and albumin levels to estimate the effect of nutritional
      status on antithrombin activity in the elderly. HC II levels were normal in the
      elderly subjects with a good nutritional state (103 +/- 18%), but were
      significantly decreased in those with malnutrition (85 +/- 15%, p less than
      0.001). AT III levels also showed the same tendency. These results indicate a
      decrease in the reserve capacity to inhibit thrombin generation at sites of
      atherosclerosis in response to trigger events. The deficiency of two major
      antithrombin factors in the elderly may indicate a tendency to thrombosis,
      especially in individuals with malnutrition. When considering the clinical
      significance of HC II, several other parameters, including age, nutritional
      status, hepatic synthetic ability, and the presence or absence of acute phase
      reaction should also be assessed.

PMID- 1381850
TI  - Modulation of heparin cofactor II activity by glycosaminoglycans and adhesive
      glycoproteins.
AB  - Heparin cofactor II (HCII) is a specific thrombin inhibitor; its inhibitory
      activity is stimulated by heparin (Hep) and dermatan sulfate (DS). Vitronectin
      (VN), a heparin binding adhesive glycoprotein present in plasma and extracellular
      matrix, has been shown to decrease the stimulatory effect of Hep but not of DS on
      thrombin inhibition by HCII (Preissner and Sie, 1988). We analyzed the effect of
      glycosaminoglycans (GAGs) and GAG-binding proteins on the HCII/thrombin
      interaction in more detail. HCII was purified from the supernatant of barium
      citrate adsorbed normal human plasma by polyethylene glycol precipitation
      followed by affinity chromatography on heparin-Sepharose CL-6B and ion-exchange
      chromatography on a QAE-Sephadex A-50. Inhibition of thrombin by HCII was studied
      in the absence and presence of GAGs (hep 0.03-30 micrograms/ml, DS 0.05-50
      micrograms/ml, heparan sulfate (HS) 0.05-50 micrograms/ml) in a chromogenic
      substrate assay using S-2366 as a thrombin substrate. The effects of VN and
      fibronectin (FN) on HCII stimulation by GAGs were determined. In addition to Hep
      and DS the inhibitory effect of HCII was stimulated by HS, however, to a lesser
      extent. Using 0.03U/ml thrombin and 1nM HCII the stimulatory effect of GAGs was
      completely inhibited when Hep (less than or equal to 0.3 micrograms/ml) was
      preincubated with VN (60 micrograms/ml) and decreased to less than 50% when HS
      (50 micrograms/ml) was preincubated with VN (60 micrograms/ml). VN had no effect
      on DS as already described previously.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381851
TI  - A longitudinal study on anthropometric and clinical development of Indian
      children adopted in Sweden. II. Growth, morbidity and development during two
      years after arrival in Sweden.
AB  - One hundred and fourteen consecutively recruited children adopted from India (60%
      girls) to Sweden were studied during 2 years after arrival, with examinations
      monthly the first 6 months and thereafter every 3 months. Sixty-two percent were
      below 1 year of age at arrival. There was a mean increase from -2.2 standard
      deviation scores (SDS) height/age to -0.7 SDS during the two years, and a similar
      development for weight/age, with no significant difference between boys and
      girls. The weight/height remained at around -0.8 throughout the study period.
      Those who had lowest height/age at arrival had the most marked catch-up, but
      remained smaller throughout the 2 years. The psychomotor development was
      initially delayed in nearly 30% of the children, mainly among those stunted
      and/or with very low weight at arrival. After 2 years the rate was at a level
      similar to Swedish children. In a sub-sample, birth weight was found to be
      correlated to subsequent height and weight development. Hepatitis B, salmonella,
      giardia lamblia, trichuris trichiura, ascaris and hymenolepis nana were still
      found in a small percentage after 2 years. Other morbidity was at the same level
      as in Swedish children. Adopted children who are stunted and/or have a very low
      weight at arrival should be followed up with special care, and infectious
      diseases found at arrival should be kept in mind for differential diagnosis at
      subsequent disease episodes.

PMID- 1381852
TI  - Basal cell hyperplasia of prostate: an elusive lesion?
AB  - We report a case of basal cell hyperplasia of the prostate accompanying benign
      prostatic hypertrophy. The histogenesis of the basal cells as well as the
      histologic features and differential diagnosis of basal cell hyperplasia are
      reviewed.

PMID- 1381853
TI  - [Quality control in the allergy laboratory--4 years "Allergy Ring Trial" in
      Austria].
AB  - In 1988 the Austrian Society for Allergology and Immunology initiated an external
      quality control program for the in vitro allergy diagnosis. In 12 mailings, 62
      sera from allergic patients were sent to selected laboratories in order to
      determine total and antigen specific IgE according to the laboratory-specific
      methods. The values for total IgE varied considerably (73.9% were within +/- 1
      SD, 94.3% within +/- 2 SD and 99.1% within +/- 2 SD, but only 0.9% beyond that).
      Sources of error were mainly attributable to inappropriate equipment and low
      quality reagents, but also bad test performance, with respect to personnel and
      the routines. In contrast, antigen specific IgE against pollen, mites, moulds,
      insect venoms, animal danders, drugs, parasites, environmental and food antigens
      revealed quite homogeneous results. Out of 1492 data, only 46 (3.1%) had to be
      declared as "wrong", and the variability of the RAST-classes was low. Whereas the
      quality of the reagents from all the different suppliers was not absolutely
      reliable at the beginning of the study, it improved considerably with time, as
      consequence of our complaints. The comparability of the methods for detecting
      total-IgE were non-satisfactory, whereas those for antigen specific IgE were
      generally good. The variety of methods employed (radio- and enzyme immunologic,
      fluoro- and nephelometric methods, etc.) should entail appropriate consequences,
      especially critical comparisons within one and the same laboratory; in addition,
      international standardization of the "normal" values should replace company
      standards, and quality control programs for each test system before it is
      marketed should be mandatory. Our results confirm, that external control should
      be obligatory for any laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381854
TI  - [Familial Mediterranean fever. Case of a 48-year-old patient with recurrent
      abdominal pain].
AB  - A 48 year-old male patient from Turkey underwent laparotomy 13 years before
      admission to one unit because of persistent pain in the upper abdomen and fever.
      Subsequently, he was repeatedly admitted to surgical departments with recurrent
      upper abdominal pain and fever. The patient was admitted for medical
      investigation to our department with fever and left pleuritic pain. During this
      observation period he repeatedly had attacks of fever lasting for one day with
      leucocytosis. The diagnosis of familial Mediterranean fever was made. Therapy
      with colchicine (1.5 mg/day) led to complete remission, maintained over the
      follow-up period of 2 years to date.

PMID- 1381855
TI  - [Various indicators of serotonin metabolism in the cerebrospinal fluid of
      patients with neurasthenia and cerebral arachnoiditis].
AB  - Thirty patients with cerebral arachnoiditis and 26 with neurasthenia were found
      to have differences in the content of serotonin, 5-hydroxyindoleacetic++ acid and
      melatonin in the cerebrospinal fluid, which depended in arachnoiditis on the
      degree of intracranial pressure elevation. The data on serotonin metabolism can
      be used in objective evaluation of the organic background in neurotic patients
      and serve for estimating the intensity of hypertension in patients with cerebral
      arachnoiditis.

PMID- 1381857
TI  - Presenile dementia with progressive supranuclear palsy tangles and Pick bodies:
      an unusual degenerative disorder involving the cerebral cortex, cerebral nuclei,
      and brain stem nuclei.
AB  - Degeneration of heterogeneous systems in the central nervous system, with
      widespread distribution of argyrophilic neuronal fibrillary inclusions, was found
      in a patient with presenile dementia. Atrophy was circumscribed in the frontal
      and temporal lobes. Neuronal loss was severe in the basal ganglia, subthalamic
      nucleus, and substantia nigra. Immunocytochemical study using anti-phosphorylated
      tau and anti-ubiquitin antibodies in conjunction with ultrastructural
      observations revealed two types of inclusions: neurofibrillary tangles (NFTs) of
      progressive supranuclear palsy (PSP) in the Edinger-Westphal nucleus, locus
      coeruleus, cerebellar dentate nucleus, inferior olivary nucleus, and posterior
      horn of the spinal cord; and Pick bodies (PBs) in the atrophied cerebral cortex
      and red nucleus. PSP-type NFTs and PBs have been demonstrated in a single case
      for the first time. Despite their pathognomonic significance in certain
      disorders, we suggest that these inclusions may reflect a form of cytoskeletal
      disorganization, which is not entirely restricted to a single disease entity.

PMID- 1381856
TI  - Ultrastructural studies of the cells forming amyloid in the cortical vessel wall
      in Alzheimer's disease.
AB  - Ultrastructural studies of serial sections of the vessels with amyloid deposits
      in the brain cortex of patients with Alzheimer's disease showed that cells in the
      position of pericytes--perivascular cells--and perivascular microglial cells are
      producers of amyloid fibrils in the vascular wall. Three types of changes from
      normal are distinguishable in the vessel wall: (1) semicircular or circular
      thickening of vascular wall containing a large amount of amorphous material and
      various number of amyloid fibrils, (2) tuberous amyloid deposits containing both
      amorphous material and amyloid fibrils, some of the fibrils being arranged in
      strata and others arranged radially, and (3) amyloid star composed of a
      predominantly radial arrangement of bundles of amyloid fibrils and a less
      prominent amorphous component. A mixture of amorphous material and amyloid
      fibrils is present in cell membrane invaginations of perivascular cells, and
      occasionally perivascular microglial cells. Bundles of amyloid fibrils are found
      in altered cisternae of the endoplasmic reticulum and in the channels confluent
      with the infoldings of the plasma membrane of perivascular microglial cells. The
      amyloid deposition in the wall of the vessel causes degeneration of endothelial
      cells and the reduction of, and in some vessels obliteration of, the vessel
      lumen. In areas affected by amyloid angiopathy, extensive degeneration both of
      the neuropil and of neurons was observed. These changes were accompanied by
      astrogliosis. This study demonstrates similarities in amyloid formation in
      amyloid angiopathy and in beta-amyloid plaques in the neuropil and suggests that
      cells of the mononuclear phagocyte system of the brain (perivascular cells and
      perivascular microglia) are engaged in amyloid fibril formation.

PMID- 1381858
TI  - Modifications in myotendinous junction structure following denervation.
AB  - Changes in the structure of myotendinous junctions in response to peripheral
      nerve lesions are examined by transmission electron microscopy and morphometric
      analysis. Modifications in the folding of the plasma membrane at myotendinous
      junctions relative to the cross-sectional area of myofibrils terminating at the
      membrane are evaluated quantitatively using a morphometric analysis in which the
      muscle cell processes at the myotendinous junction are modeled as circular
      paraboloids. Denervated frog semitendinosus muscles were analyzed at 2, 4 and 8
      weeks following denervation and compared to innervated, contralateral controls.
      No significant differences were found in relative folding of junctional plasma
      membranes between any two data sets, although myofibril diameter decreased over
      time following denervation. This shows that junctional plasma membrane and
      associated junctional structures, such as basement membrane, are removed from the
      myotendinous junction at a rate similar to that of myofibril thinning, thereby
      keeping constant the ratio between junction area and myofibril cross-sectional
      area. Electron microscopic observations indicate that 4 weeks post-denervation is
      the most active stage of junction remodeling of the time points sampled.

PMID- 1381859
TI  - Infectivity of human T-lymphotropic virus type I to human nervous tissue cells in
      vitro.
AB  - Infectivity of human T-lymphotropic virus type I (HTLV-I) to human nervous tissue
      cells was explored using co-cultivation with X-irradiated, HTLV-I-producing MT2
      cells. Examined cells included normal cerebellar cells, brain tumor cells
      (astrocytoma, medulloblastoma, meningioma, hemangioblastoma, and schwannoma), and
      various cell lines (astrocytoma, ependymoma, oligodendroglioma, medulloblastoma,
      and neuroblastoma). Successful HTLV-I infection was confirmed
      immunohistochemically using monoclonal antibodies to HTLV-I p19, p24, and pX
      product. All cell lines and primary cultures from normal cerebellar tissues and
      brain tumors could be infected with HTLV-I. Double immunostaining showed that
      glial fibrillary acidic protein-, S-100 protein- or vimentin-positive cells were
      susceptible to infection. Neurofilament- or neuron-specific enolase-positive
      cells in medulloblastoma could also be infected. Reverse-transcriptase assay
      revealed the productive infection in U251-MG (astrocytoma) and KG-IC
      (oligodendroglioma) lines. Co-cultivated U251-MG cells formed syncytial
      polykaryons after serial passages, and polymerase chain reaction assay detected
      HTLV-I genome in U251-MG syncytial polykaryons and p19+ mononuclear cells. HTLV-I
      viral RNA was also detected in infected U251-MG cells by in situ hybridization.
      These data show that HTLV-I may have a wide spectrum of infectivity in human
      nervous tissues.

PMID- 1381860
TI  - Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase
      alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer
      region counts.
AB  - The growth potential of 65 pituitary adenomas was determined by histochemical
      analysis with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies,
      bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar
      organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs)
      determined by Ki-67 and anti-DNA polymerase alpha and the BrdUdR labeling index
      (LI) were generally very low [1.0 +/- 0.2%, 1.1 +/- 0.2%, and 0.5 +/- 0.1% (+/-
      SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas,
      which had significantly higher indices, there were no statistically significant
      differences in the indices among the other subtypes of pituitary adenomas.
      Recurrent tumors had higher Ki-67 and DNA polymerase alpha PCIs and BrdUdR LIs
      (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P less than 0.005). The
      number of Ag-NORs did not correlate significantly with any of the three indices.
      The mean number of Ag-NORs was higher in nonfunctioning adenomas than in
      functioning adenomas (2.04 vs 1.66, P less than 0.005); among prolactin-positive
      adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than
      untreated tumors (1.75 vs 1.57, P less than 0.005). These results suggest that
      the Ki-67 and DNA polymerase alpha PCIs and the BrdUdR LI predict the growth
      potential of individual pituitary adenomas, whereas the number of Ag-NORs appears
      to correlate with hormone production rather than with the proliferative
      potential.

PMID- 1381861
TI  - Neuronal damage, glial response and cerebral metabolism after hypothermic
      forebrain ischemia in the rat.
AB  - We investigated the effect of 30 degrees C whole body hypothermia on neuronal
      injury, astroglial reactivity and intracellular pH in rats subjected to 15 min of
      forebrain ischemia. Experimental groups included: (1) normothermic ischemia (n =
      8), ischemia induced under 37 degrees C body temperature, (2) hypothermic
      ischemia (n = 6), ischemia induced under 30 degrees C body temperature. Cerebral
      intracellular pH was measured using in vivo 31P NMR spectroscopy over 7 days.
      Neuronal injury and astrocytic reactivity were evaluated using hematoxylin and
      eosin staining, and immunoreactivity to glial fibrillary acidic protein,
      respectively. Normothermic animals revealed significant alkalosis (P less than
      0.01) at 48 h after ischemia compared to the pre-ischemic value. No significant
      intracellular pH change was detected after ischemia in the hypothermic group.
      Ischemic neuronal injury was prevented in the hypothermic animals, compared to
      the severe neuronal injury found in the normothermic animals (P less than 0.01).
      The marked astrocytosis of normothermic animals was significantly inhibited in
      the hypothermic animals (P less than 0.01). Our data indicate, that hypothermia
      significantly inhibits neuronal injury as well as post-ischemic alkaloids and
      astrocytosis, induced by 15 min of forebrain ischemia in the rat.

PMID- 1381862
TI  - Muscle pathology correlates with permanent weakness in hypokalemic periodic
      paralysis: a case report.
AB  - We present a morphological follow-up in a case of familial hypokalemic periodic
      paralysis with progressive weakness. At age 12 years muscle biopsy revealed mild
      vacuolar changes. Seventeen years later, after the patient had developed
      permanent weakness, light and electron microscopy disclosed tubular aggregates in
      about 15% of the fibers and medium-grade myopathic alterations. We describe
      correlation of muscle pathology with permanent weakness in hypokalemic periodic
      paralysis.

PMID- 1381863
TI  - [The effect of sodium-4-[2-(2,3-dimethyl-4-[1-(4-
      isobutylphenyl)ethoxy]benzolamino)phenoxy] butyrate (ONO-3805) and antiandrogenic
      agents on the rat accessory sex organs].
AB  - The effects of sodium-4-[2-(2,3-dimethyl-4-[1-(4-isobutylphenyl)
      ethoxy]benzolamino)phenoxy]butyrate (ONO-3805), newly developed as a non
      steroidal 5 alpha-reductase inhibitor, on rat accessory sex organs was compared
      with chlormadinone acetate (CMA) and non-steroidal antiandrogen, flutamide (FLU).
      ONO-3805 demonstrated excellent antiandrogenic activity which was similar to that
      of CMA in reducing the accessory sex organ weight. Moreover this agent did not
      show any significant effects on the serum testosterone level, but CMA and FLU
      changed it significantly. We previously reported the androgenic activity of
      antiandrogen (CMA, FLU, AA560, cyproterone acetate, medroxy progesterone,
      estrogen), but ONO-3805 is free of androgenic activity.

PMID- 1381864
TI  - [Papillary adenocarcinoma of the prostate with good response to antiandrogen
      therapy and delayed radiotherapy: a case report].
AB  - A 76-year-old man complained of initial hematuria and dysuria. Right lobe of the
      prostate was elastic soft, enlarged and hypoechoic. The serum levels of PA and
      gamma-Sm were abnormally high. Prostatic biopsy showed papillary adenocarcinoma
      which was stained by prostatic specific antigen (PA). The cancer was clinically
      diagnosed as stage C. Antiandrogen therapy was performed. After three months, the
      prostatic tumor markers decreased to the normal range and the tumor reduced in
      size without any findings of metastasis on CT scan. Because prostatic biopsy
      showed viable cancer cells, radiotherapy was added. After six months, the tumor
      reduced in size without any signs of metastasis on CT scan and prostatic biopsy
      revealed no viable cancer cells or elevation of the tumor markers. The positive
      staining for PA and the good response to antiandrogen therapy in our case support
      the view that papillary adenocarcinoma of the prostate is only a morphologic
      variant of ordinary prostatic carcinoma (acinous adenocarcinoma).

PMID- 1381865
TI  - Papillary cystoadenocarcinoma of the prostate.
AB  - We report a papillary cystadenocarcinoma of the prostate found in a 66-year-old
      man presenting with gross hematuria. The tumor was identified as prostatic in
      origin because of positive immunohistochemical staining of prostate specific
      antigen.

PMID- 1381866
TI  - [Determination of ER-D5 (estrogen receptor related antigen) in prostatic cancer
      and its significance].
AB  - The existence of an estrogen receptor and various other sex steroid receptors has
      been confirmed in prostatic cancer. However, the action mechanism of hormone
      therapy and relationship between the disappearance of hormone response, which is
      observed in the recurrence of prostatic cancer, and various sex steroid receptors
      have yet to be identified. The use of monoclonal antibody ERICA is known as a
      method of detecting the estrogen receptor in the immuno-histological chemistry
      method. However, this monoclonal antibody is difficult to use on paraffin
      sections. Therefore, using monoclonal antibody D5, which allows ER-D5 detection
      of the estrogen receptor related antigen on paraffin sections, we investigated
      whether or not estrogen receptors are present in the prostatic cancer preparation
      and studied the survival rate of prostatic cancer as well as relationship with
      recurrence. Positive ER-D5 results were obtained in 37 of 93 prostatic cancer
      cases (39.8%) and in all 20 prostatic hypertrophy cases (100%). ER-D5 tended to
      be more densely stained in prostatic hypertrophy than in prostatic cancer. The
      survival rate was obviously higher in the ER-D5 positive prostatic cancer cases
      than in ER-D5 negative cases for a certain period of time after the start of
      treatment. Despite differences in the histo-differentiation degree and clinical
      stage of prostatic cancer, the ER-D5 positive percentage did not change and
      remained between 35% and 45%. In cases where another prostatic cancer preparation
      was taken because of recurrence of prostatic cancer, there were no ER-D5 positive
      cases at the time of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381867
TI  - [A case of urinary bladder hernia].
AB  - A 77-year-old male visited our hospital complaining of swelling in the right
      scrotal and inguinal region, urinary urgency and difficulty of urination.
      Physical examination revealed an elastic soft mass in the right inguinal region
      toward the right scrotum. Rectal examination proved that the prostate was
      moderately enlarged. Cystogram and urethrography showed hernia of the bladder
      into the right scrotum and benign prostatic hyperplasia. Urodynamic studies
      demonstrated organic obstruction in the lower urinary tract. Transurethral
      resection of the prostate was done for benign prostatic hyperplasia. Later,
      surgical treatment for the bladder hernia was performed by replacing the bladder
      into the pelvic cavity and closing the hernial ring without resection of the
      bladder wall. The bladder hernia proved to be a para-peritoneal type. The
      postoperative course was uneventful. The previous reports of urinary bladder
      hernia are reviewed and the incidence, etiology, diagnosis the treatment are
      discussed.

PMID- 1381868
TI  - [A case of giant prostatic calculi].
AB  - A 83-year-old man was admitted because of fever and painful swelling of the right
      scrotal contents on January 23, 1989. Kidney-ureter-bladder X-ray (KUB) showed
      multiple big prostatic calculi which were compressed postero-laterally by benign
      prostate hyperplasia (BPH) according to the CT film. UCG film revealed urethral
      stricture in the anterior urethra. He was diagnosed as having right epididymitis,
      urethral stricture, BPH and giant prostatic calculi. He was treated with right
      orchiectomy, urethral bougie and suprapubic prostatectomy with removal of the
      calculi. The total weight of the prostatic calculi was 28 g of consisted of 125
      pieces. The postoperative course was uneventful and two years after the operation
      he has been well and free from evident disease.

PMID- 1381870
TI  - [Clinical evaluation of oral ofloxacin in 3-day therapy for transurethral
      resection of the prostate].
AB  - The effectiveness of oral administration of an antibacterial alone was compared
      with that of intravenous administration of an antibiotic in patients with benign
      prostatic hyperplasia undergoing transurethral resection of the prostate (TUR-P).
      In group A (23 patients), surgery was carried out by administering 200 mg of
      ofloxacin (OFLX) alone, during the day before surgery and in the morning of the
      day of surgery and three times a day from the morning after surgery for two days,
      making the total dose 1,800 mg, and total period of administration 3 days. In
      group B (22 patients), 1 g of Cefotetan (CTT) was intravenously infused twice a
      day for 3 days from the operative day, making the total dose 6 g. The patients in
      both groups were given no other antibacterials or antibiotics. The maximum body
      temperature was recorded for post-operative 2 weeks. Negativization of bacteria
      by bacterial culture in the urine and disappearance of the pyria, were followed
      up on an outpatient bases. The mean maximum body temperature up to post-operative
      week 2 was 37.1 +/- 0.3 degrees C and 37.0 +/- 0.3 degrees C in groups A and B,
      respectively. The mean number of days required until negativization of bacteria
      in the urine was 41.5 +/- 38.9 days and 43.3 +/- 24.9 days in groups A and B,
      respectively. The mean number of days required until disappearance of the pyuria
      was 76.5 +/- 23.0 days and 68.2 +/- 17.9 days in groups A and B, respectively. No
      significant differences were noted by Student's t-test between groups A and
      B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381869
TI  - [A multicenter, fixed-flexible dose study of terazosin hydrochloride in the
      treatment of symptomatic benign prostatic hypertrophy].
AB  - In this study the multicenter, fixed-flexible dose regimen was taken to evaluate
      the effective dose range of Terazosin for the treatment of micturition
      disturbance in benign prostatic hypertrophy (BPH) and to clarify the
      characteristics of patients who are more responsive to Terazosin therapy. After a
      1-week washout (placebo) the first two weeks 1 mg/day of Terazosin was
      administered, then depending on efficacy of subjective symptoms, Terazosin doses
      were increased up to 2 mg/day and 4 mg/day at intervals of two weeks. After six
      weeks the final efficacy and safety were assessed. The subjective symptom
      improvement rate was 18.5% by 1 mg/day, 55.6% by 2 mg/day and 65.4% by 4 mg/day
      cumulatively. The objective symptom improvement rate were 13.2% by 1 mg/day,
      42.1% by 2 mg/day and 50.0% by 4 mg/day cumulatively. The global improvement rate
      was 14.5% by 1 mg/day, 50.0% by 2 mg/day and 61.8% by 4 mg/day cumulatively. The
      patients who had a higher subjective symptom score in the lead-in period were
      more improved rather than those who had a lower score. In objective symptoms,
      voided volume, maximum flow rate (MFR), MFR nomogram score and average flow rate
      improved and the ratio of residual urine volume decreased. There was no
      relationship between clinical improvement on either subjective or objective
      symptoms and prostatic weight. Adverse reactions, such as dizziness, vertigo,
      tinnitus, nausea and blurred vision; were seen in 10 cases. In conclusion
      Terazosin was effective and well tolerated for the treatment of patients who had
      micturition disturbance with BPH in the dose range of 2 to 4 mg/day.

PMID- 1381871
TI  - Compatibility of bupivacaine hydrochloride with hydromorphone hydrochloride or
      morphine sulfate.

PMID- 1381872
TI  - Staining for enzymatic activity after gel electrophoresis, I.

PMID- 1381873
TI  - Development of solid-phase enzyme-linked immunosorbent assays for the
      determination of epidermal growth factor receptor and pp60c-src tyrosine protein
      kinase activity.
AB  - Solid-phase ELISAs for the determination of EGF receptor (EGF-R) and pp60c-src
      tyrosine protein kinase activity are described. The methods were developed and
      optimized using purified recombinant EGF-R intracellular domain (ICD) and pp60c
      src tyrosine protein kinases. A standardized assay that utilizes poly (GluNa
      Tyr)4:1 as substrate and a monoclonal antiphosphotyrosine antibody for detection
      is described. Assay conditions for both enzymes were optimized with respect to
      substrate and ELISA plate-coating condition, divalent metal ion preferences,
      enzyme concentration, apparent kinetic constants for ATP, and reaction linearity.
      Following standardization, a number of reference tyrosine protein kinase
      inhibitors were tested in the ELISAs and compared to results obtained using
      solution-phase radioactive tyrosine protein kinase assays, which are based on the
      transfer of 32P from [gamma-32P]ATP to synthetic substrate. To enable a
      comprehensive comparison, IC50 values obtained in the ELISA were compared with
      values obtained in radioactive assays using both the holo-EGF-R and EGF-R ICD
      kinases. No substantial qualitative differences between these assays were seen.
      For many routine tyrosine protein kinase assays, semiquantitative or qualitative
      measurement of TPK activity is adequate. For such purposes, the ELISAs would be
      an attractive alternative to radioactive assays.

PMID- 1381874
TI  - Exogenous primer-independent cDNA synthesis with commercial reverse transcriptase
      preparations on plant virus RNA templates.
AB  - Upon reverse transcription and cloning manipulations with virion RNAs of several
      plant viruses, namely beet yellows virus, brome mosaic virus, and potato virus X,
      we came across a significant background synthesis of cDNA on the virion RNA
      template in vitro independent of exogenous primers added. When tested with beet
      yellow virus RNA template, several commercial preparations of avian
      myeloblastosis virus (AMV) reverse transcriptase showed the background activity
      monitored by the [alpha-32P]dNTP incorporation in vitro, while the enzyme from
      murine moloney leukemia virus (MMLV) was found strictly exogenous-primer
      dependent. To detect possible nucleic acid contaminations in reverse
      transcriptase, the enzyme preparations from several commercial sources were
      incubated with [gamma-32P]ATP and polynucleotide kinase. The labeled material
      from AMV reverse transcriptase preparations comigrated with a tRNA marker in
      polyacrylamide gels and was found to be RNase-sensitive. The MMLV reverse
      transcriptase preparations were free from such a contamination. These results
      indicate that the exogenous-primer-independent cDNA synthesis by some AMV reverse
      transcriptases could be due to a contaminating tRNA (or its low-molecular-weight
      degradation products) serving as an endogenous primer.

PMID- 1381876
TI  - Molecular weights of glycosylated and nonglycosylated forms of recombinant human
      stem cell factor determined by low-angle laser light scattering.
AB  - The molecular weight of recombinant human stem cell factor (SCF) was determined
      using a low-angle laser light scattering combined with a differential
      refractometer and a uv detector. The protein samples were applied to these
      detectors through a gel filtration column by a high-performance liquid
      chromatographic pump. The Chinese hamster ovary (CHO) cell-derived SCF gave a
      molecular weight of 53,000 for the entire molecule and 35,000 for the protein
      moiety only at pH 7.0, indicating that the CHO cell-derived protein is
      glycosylated by 34%. Since the molecular weight of the polypeptide is 18,600, the
      results demonstrate that the CHO cell-derived SCF forms a dimer. The molecular
      weight of Escherichia coli-derived SCF was determined to be 39,000, similar to
      the above value (35,000). Essentially identical molecular weights were obtained
      at pH 3.0, indicating no dissociation of the dimer.

PMID- 1381875
TI  - Centrifugal elutriation of large fragile cells: isolation of RNA from fixed
      embryonic blastomeres.
AB  - In order to analyze the RNA populations present in different cells of very early
      embryos, we have developed a protocol to purify these large blastomeres using
      counterflow centrifugal elutriation (CCE). This procedure employs ethanol
      fixation to stabilize the cells against shear forces encountered during CCE.
      Using this method, we fractionated the three different blastomere types of the 16
      cell sea urchin embryo, the micromeres, mesomeres, and macromeres, achieving 96,
      94, and 96% mean purities, respectively. We show here that intact RNA is
      recovered with equal efficiency from each blastomere preparation. Using this
      method, we have identified several RNAs that are distributed non-uniformly among
      these cells.

PMID- 1381877
TI  - Management of an outbreak of Norwegian scabies.
AB  - An outbreak of Norwegian scabies in a 170-bed acute care hospital was controlled
      through an organized plan for delivering treatment to those affected: four
      patients, 50 staff members, and 14 family members of staff members. Health
      departments in two counties were notified and found four additional cases in the
      long-term care facility at which the index patient lived. Contact isolation was
      used for the index patient and any other patients with nosocomial scabies. Staff
      members infested with Sarcoptes scabiei were released from work until they had
      been treated with lindane. Staff members who had been in contact with infested
      persons and staff members' families were treated prophylactically with lindane.
      This aggressive treatment plan resulted in rapid resolution of the outbreak.

PMID- 1381878
TI  - Neutrophil activation associated with increased neutrophil acyloxyacyl hydrolase
      activity during inflammation in cattle.
AB  - Acyloxyacyl hydrolase (AOAH) is a lysosomal enzyme found in neutrophils and
      macrophages that acts to partially deacylate the lipid-A component of the
      endotoxin of gram-negative bacteria rendering it less toxic, yet maintaining much
      of its immunostimulatory potential. We have found that the activity of neutrophil
      AOAH per cell increased during localized inflammation. The purpose of this study
      was to determine the mechanism(s) responsible for these increases in neutrophil
      AOAH activity. Because changes in neutrophil maturity commonly are associated
      with inflammation, intravascular infusion of purified gram-negative bacterial
      lipopolysaccharide and SC injection of bovine recombinant granulocyte colony
      stimulating factor was used to induce large numbers of circulating immature
      neutrophils. Immature neutrophils were found to have AOAH activity equal to that
      of mature cells; however, when neutrophils were stimulated in vitro with known
      activators, AOAH activity of activated cells was more than that of unstimulated
      cells. The increase in AOAH activity was inversely related to prestimulation
      activity. Increases in AOAH activity after neutrophil activation were not a
      result of de novo synthesis of the enzyme, because cycloheximide did not prevent
      activation-induced increases in activity.

PMID- 1381879
TI  - Culture and initial characterization of the secretory response of neoplastic cat
      mast cells.
AB  - Mast cells isolated from feline splenic mastocytomas were cultured to study their
      structural and functional properties. Isolated cells from various cats were grown
      as monolayer cultures for a mean of 56 days (range, 30 to 76 days). Cat mast
      cells released allergic mediators in response to compound 48/80, anti-cat serum
      antibodies, and concanavalin A. On the basis of the finding that secretion from
      cat mast cells was stimulated by anti-cat serum antibodies and concanavalin A,
      these cells contain surface-bound immunoglobulins. The presence of mast cell
      sensitizing antibodies has been suspected in cats, but never before directly
      demonstrated. Cultured cat mast cells have cytochemical and functional
      characteristics common to connective tissue-type mast cells and provide one of
      the few non-rodent models of cultured cells for the study of this type of mast
      cell.

PMID- 1381880
TI  - Immunologic responses in healthy random-source cats fed N,N-dimethylglycine
      supplemented diets.
AB  - The immunomodulatory capacities of N,N-dimethylglycine (DMG) were examined in
      random-source cats. Blood mononuclear leukocytes of healthy adult cats that had
      negative results to tests for FeLV and feline immunodeficiency virus were exposed
      in vitro to various concentrations of DMG (10 to 1,000 micrograms/ml) and were
      evaluated for proliferative responses to T- or B-cell phytomitogens. Although
      increased, mean lymphocyte blastogenic responses to phytolectins in DMG-treated
      cultures did not differ significantly from responses of untreated cultures. For
      in vivo studies, cats were given a solution containing either 100 mg of DMG or a
      control solution without DMG orally at 8 AM and 6 PM for 40 consecutive days. On
      post-treatment day 24 and 25, mean blastogenic responses to phytolectins in DMG
      treated and control cats inoculated 10 days earlier with an inactivated feline
      virus vaccine were similar. Cats given DMG and inoculated twice in a 3-week
      interval with a commercial vaccine containing inactivated feline herpesvirus-1
      and feline calicivirus had significantly (P = 0.045) lower virus neutralizing
      serum antibody titers against feline herpesvirus-1, compared with titers of
      control cats, whereas feline calicivirus titers were similar in both groups. On
      day 25, mean serum interferon activity, induced after IV inoculation of Newcastle
      disease virus, was significantly (P = 0.021) lower in the DMG-treated cats.
      Results of this study of DMG in healthy cats failed to demonstrate enhancement of
      either specific or nonspecific immunity.

PMID- 1381881
TI  - Serum amylase activity and calcium and magnesium concentrations in young cattle
      grazing fescue and Bermuda grass pastures.
AB  - The study reported here was part of a long-term investigation of the effects of
      genotype on growth, reproduction, and metabolism in cattle grazing common Bermuda
      grass and endophyte-infected fescue pastures. In June 1990, blood samples were
      collected from the tail vein of yearling heifers and steers (Angus [AA], Brahman
      [BB], and their reciprocal crosses [AB, BA], n = 97). Serum amylase activity was
      assayed enzymatically; serum Ca and Mg concentrations were determined by atomic
      absorption spectrophotometry. The effects of endophyte-infected fescue depended
      on genotype (P less than 0.001). In yearlings having at least 1 Angus parent (AA,
      AB, BA), grazing endophyte-infected fescue was associated with higher serum
      amylase activity than was grazing Bermuda grass. But serum amylase activities of
      BB yearlings consuming either forage were similar. Moreover, for either forage,
      substantial differences were related to genotype (P less than 0.007) and gender
      (P less than 0.05). Angus yearlings had higher serum amylase activity than did
      Brahman yearlings; AB and BA yearlings had intermediate values. Heifers had
      higher amylase activity than did steers. The relationship among serum values of
      amylase, Ca, and Mg depended on forage. Yearlings consuming endophyte-infected
      fescue and having at least 1 Angus parent had a moderate negative correlation
      between serum amylase activity and Ca concentration (r = -0.53; P less than
      0.0005); that is, in calves of genotypes with increased amylase activity while
      consuming endophyte-infected fescue (AA, AB, BA), the higher the amylase
      activity, the lower the serum Ca concentration. However, in yearlings consuming
      Bermuda grass, serum amylase and Ca values were not correlated.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1381882
TI  - Severe pancreatico-duodenal injuries: the effectiveness of pyloric exclusion with
      vagotomy.
AB  - The operative management and clinical course of 17 patients treated for severe
      pancreatico-duodenal injuries from 1983 to 1990 was reviewed. The etiology of
      these injuries was gunshot wound in 15 patients; stab wound in 1 patient; and a
      motor vehicle accident in 1 patient. Seven patients presented in shock with a
      systolic blood pressure of less than 80. At exploration, 57 associated injuries
      were found in the 17 patients including 16 major vascular injuries. All patients
      were treated with pyloric exclusion and drainage. Vagotomy was performed in eight
      patients. None of these 17 patients were felt to have extensive enough damage to
      require pancreatico-duodenectomy. Two patients died in the immediate
      postoperative period of severe coagulopathy and two patients died of sepsis.
      Seven patients had complications related to the pancreatico-duodenal injury. All
      seven developed pancreatic fistulas; three also had pancreatitis and two
      developed multiple enterocutaneous fistulas. Systemic complications included
      pulmonary complications in eight patients and sepsis in five patients, including
      two patients with abdominal abscesses. Six patients bled in the immediate
      postoperative period secondary to coagulopathy. Three patients had complications
      related to pyloric exclusion. One developed afferent loop syndrome necessitating
      reoperation. The other two had marginal ulcers, which either perforated or bled
      and required reoperation. Of interest, neither of these two patients had vagotomy
      initially. The results of this series confirm the effectiveness of pyloric
      exclusion with vagotomy for severe pancreatico-duodenal injury.

PMID- 1381883
TI  - What is going to happen tomorrow in the field of soluble anti-nuclear antigen
      antibodies?

PMID- 1381884
TI  - Ring chromosome 17. Case report and review of the literature.
AB  - A 46,XX,r(17) karyotype was observed in a 9-year-old infant with short stature,
      moderate mental retardation but without other physical abnormality. Eight cases
      with an r(17) have since been reported: 4 can be compared with our patient, one
      was detected by amniocentesis, and 3 have Miller-Dieker syndrome. Submicroscopic
      deletions in the subband p13.3 are probably the cause of Miller-Dieker syndrome.
      They are present in some cases of r(17) but, in others, this short arm region is
      entirely preserved.

PMID- 1381885
TI  - Sickle cell anaemia in Sudan: clinical findings, haematological and serum
      variables.
AB  - Ninety homozygous patients with Hb S haemoglobinopathy from Sudan were reported
      with respect to clinical findings, haematological and serum parameters. For
      comparison, 27 Hb AS heterozygous subjects and 28 Hb AA controls were
      investigated also. The patients showed an extreme type of illness presenting with
      severe clinical signs such as dactylitis, liver enlargement and cardiac
      complications. There was marked haemolytic anaemia (mean haemoglobin 66 g/l).
      Some patients also presented with low serum (S)-iron levels, indicating iron
      deficiency. S-bilirubin, S-ASAT, S-ALAT, S-GT and S-urate were notably raised,
      most probably as a consequence of haemolysis with liver involvement. The patients
      had lower S-calcium levels when compared with the AS and AA subjects. This may
      suggest a possible role of HB S in the production of this feature.

PMID- 1381886
TI  - Multi-drug-resistant Salmonella typhi--a need for therapeutic reappraisal.
AB  - Enteric fever caused by Salmonella typhi resistant to all the standard first-line
      antibiotics is emerging as a major problem in developing countries. Fifteen such
      culture-proven cases were treated with ceftriaxone (6), cefotaxime (5) or
      ciprofloxacin (4). The earliest defervescence occurred with ceftriaxone (mean 3.3
      days). Clinical cures were obtained with all three drugs with only one child
      having a relapse. Ciprofloxacin, by virtue of its cost and an oral route of
      administration, is the ideal choice in a developing country.

PMID- 1381888
TI  - Prognostic factors influencing mortality in meningococcal meningitis.
AB  - The clinical features and some laboratory parameters of 247 cases of
      meningococcal meningitis admitted between January 1983 and April 1990 to a
      paediatric ward in Jawahar Lal Nehru Medical College Hospital, India were
      analyzed retrospectively. A total of 189 (76.5%) were more than 5 years of age.
      The maximum number of cases occurred between October and April each year.
      Complications included bleeding tendencies, neurological deficits, gangrene of
      limbs, arthritis, uveitis and cataract. The overall mortality rate was 16%. A
      scoring system based on some clinical characteristics correctly predicted a fatal
      outcome in all but three children.

PMID- 1381887
TI  - A study of bacterial meningitis in Kumasi, Ghana.
AB  - A prospective study of acute bacterial meningitis in infants and children in
      Kumasi, Ghana identified 69 cases by culture or antigen detection. Of these,
      50.7% (n = 35) were S. pneumoniae, 34.8% (n = 24) N. meningitidis and 14.5% (n =
      10) H. influenzae. The mortality for each pathogen was 36.4%, 17.4% and 30%,
      respectively, showing no significant difference. In pneumococcal meningitis, the
      most significant clinical factor associated with an increased mortality rate or
      subsequent neurological sequelae was a lowered level of consciousness at
      admission (chi 2 = 8.66, d.f. = 1, p = 0.003). Antibiotic susceptibilities were
      determined in the 40 positive isolates. Six cases of N. meningitidis and two of
      S. pneumoniae were penicillin-resistant, and there was a single case of
      chloramphenicol-resistant S. pneumoniae.

PMID- 1381889
TI  - Hyperparasitaemia: not a reliable indicator of severity or poor prognosis in
      falciparum malaria in children in endemic African countries.
AB  - Hyperparasitaemia as an indicator of severity or poor prognosis in falciparum
      malaria and response to oral antimalarial therapy were evaluated in an outpatient
      study of 77 consecutive African children from an endemic area. At presentation,
      clinical illness was graded as mild in 37, moderate in 14 and severe in 26. There
      was no evidence of renal, hepatic or cerebral complications. Clinical response to
      oral antimalarial drugs was characterized by rapid and uneventful recovery from
      illness in all but one patient who required hospital admission with prompt
      clearance of parasitaemia and fever within 96 hours. It is concluded that greater
      than 5% parasitaemia may be well tolerated by semi-immune African children. Semi
      immune subjects with hyperparasitaemia and no other evidence of severe or
      complicated disease in an endemic area may well be treated with oral
      antimalarials providing the infecting strain is fully sensitive to the drug
      chosen and the drug is rapidly absorbed.

PMID- 1381890
TI  - Visceral leishmaniasis in Libya--review of 21 cases.
AB  - Visceral leishmaniasis is an important public health problem in Libya, but its
      exact prevalence is not known. Prompted by the paucity of information in the
      literature relevant to Libyan children, we reviewed the records of 21 children
      treated at El-Fatah Children's Hospital, Benghazi between March 1982 and May
      1990. Visceral leishmaniasis was diagnosed on the basis of the history, physical
      findings and confirmatory laboratory tests including examination of bone marrow.
      The duration of illness before seeking medical advice ranged from 3 months to 1.5
      years. The commonest presenting features were fever, abdominal distension,
      anorexia with weight loss, hepatosplenomegaly and pallor. The consistent
      laboratory findings were anaemia with reticulocytosis and normal serum iron,
      neutropenia, thrombocytopenia, high ESR and hyperglobulinaemia. The bone marrow
      was positive for L. donovani in 86% of cases and the indirect haemagglutination
      test was positive in all patients. Bronchopneumonia was the most common
      complication and responded rapidly to antibiotics. All patients were treated with
      sodium stibogluconate 10 mg/kg/day. There were no major side-effects or
      complications of drug therapy. The relative paucity of cases and their late
      presentation may reflect a lack of awareness of the occurrence of visceral
      leishmaniasis by doctors in the community.

PMID- 1381892
TI  - Alterations in serum electrolytes in congenital hypertrophic pyloric stenosis: a
      study in Nigerian children.
AB  - This is a retrospective analysis of serum electrolyte values recorded at
      presentation in 20 infants who had pyloromyotomy for congenital hypertrophic
      pyloric stenosis (CHPS) during a 5-year period at Ahmadu Bello University
      Teaching Hospital, Zaria, Nigeria. All patients showed disturbance of the normal
      serum electrolyte pattern which, with one exception, was characterized by
      metabolic alkalosis associated with normal potassium levels in cases presenting
      early and metabolic alkalosis with hypokalaemia in cases presenting 3 weeks or
      later from the onset of symptoms. Late presentation of CHPS occurred much more
      frequently in this series than is reported from Europe and America.

PMID- 1381891
TI  - Lymphadenopathy and hepatosplenomegaly in the 1st year in children infected by
      HIV-1 in Zaire.
AB  - The children of 50 women positive for antibody to human immunodeficiency virus
      type 1 (HIV-1) and 42 children of antibody-negative mothers were examined for
      lymphadenopathy and hepatosplenomegaly at 3-month intervals during the 1st year
      of life. Lymphadenopathy was found to be significantly more frequent at 6 months
      (p less than 0.01), 9 months (p less than 0.001) and 12 months (p less than 0.01)
      in children who were subsequently shown to be infected with HIV-1. Hepatomegaly
      was seen more frequently (p less than 0.05) in the 1st year in HIV-1-infected
      children than in uninfected children. Splenomegaly was not more frequent in HIV-1
      infected children in this area which is holoendemic for falciparum malaria.

PMID- 1381893
TI  - Hypokalaemic paralysis in malnourished children.
AB  - Six malnourished children presenting with acute flaccid paralysis caused by
      hypokalaemia are described. Their ages ranged from 6 to 36 months. The extent of
      paralysis varied from neck flop to quadriparesis. Two cases had respiratory
      paralysis requiring ventilatory support for 48-72 hours. All were successfully
      treated with potassium supplementation. Hypokalaemia should be considered in the
      differential diagnosis of acute flaccid paralysis in malnourished children.

PMID- 1381894
TI  - Comparison of an in vitro faecal hydrogen test with the lactulose breath test:
      assessment of in vivo hydrogen-producing capability in Burmese village children.
AB  - In the assessment of carbohydrate malabsorption, it is important to determine if
      patients with a flat breath hydrogen (H2) response to an absorbable carbohydrate
      challenge are capable of producing H2. We compared the reliability of a rapid
      faecal incubation system with the lactulose breath test to assess in vivo H2
      production in 64 children. Overall, 70% of subjects were in vivo H2-producers,
      with breath H2 peaks greater than 10 parts per million within 3 h of ingesting 10
      g of the non-absorbable disaccharide lactulose. Faecal specimens from the 64
      children had a mean (SE) pH of 5.0 (0.077). Faecal homogenates were incubated
      with lactulose at both the initially measured faecal pH and at neutral pH. In
      predicting a normal in vivo H2-producing ability (sensitivity), the faecal H2
      test was correct in only 22% (faecal pH) to 44% (pH7) of cases. In predicting an
      abnormal lactulose breath test result (specificity), faecal homogenate analysis
      was correct in 53% of cases, at both faecal and neutral pH. These findings
      indicate that the faecal hydrogen test is unsuitable as a screening test for in
      vivo H2 production.

PMID- 1381895
TI  - Nosocomial respiratory syncytial virus infection in a newborn nursery.
AB  - The nosocomial spread of respiratory syncytial virus (RSV) was studied in a
      newborn nursery in Benin City, Nigeria at a time the virus was known to be highly
      prevalent in the community. Nasopharyngeal washings were obtained from babies on
      admission and, thereafter, every 4 days until discharged. Questionnaires were
      administered to medical personnel with upper respiratory tract infection (URTI).
      RSV was detected by an ELISA technique. A total of 56 babies were studied, made
      up of 33 preterm and 23 full term babies. Fourteen of the 56 babies (25%)
      developed RSV infection. Eleven babies (20.8%) acquired the infection
      nosocomially. The infected babies were all symptomatic and some had significant
      morbidity. One preterm baby died following acquisition of RSV. The study
      demonstrated that medical personnel working in our newborn nursery were a major
      contributor to the spread of nosocomial RSV infection. Babies hospitalized for
      more than 4 weeks were more likely to acquire RSV infection. Control measures are
      outlined for the reduction of nosocomial spread of RSV infection in our newborn
      nursery.

PMID- 1381896
TI  - Arm/head ratio in the nutritional evaluation of newborn infants: a report of an
      African population.
AB  - A total of 848 appropriate-for-gestational age (AGA) infants were recruited for
      the study, and fully analysed, from three hospitals in Benin City, Nigeria. They
      were examined in order to develop a standard of arm/head ratio for nutritional
      assessment of the newborn in an African population. The anthropometric
      measurements were correlated with gestational age and the standard was developed
      from the regression line of arm/head ratio and gestational age and the
      corresponding 95% confidence belt. There was a highly significant positive
      correlation between arm/head ratio and gestational age (r = 0.89; p less than
      0.001). Using clinical nutritional status as the reference, the standard had a
      good sensitivity of 85.5% and a specificity of 92.9%. Comparatively, age, weight
      classification had a sensitivity and a specificity of 67.7% and 85.3%,
      respectively. The arm/head ratio is simple and reliable. It is recommended for
      routine use, particularly in an African population.

PMID- 1381897
TI  - Concentration of fat, protein, lactose and energy in milk of mothers using
      hormonal contraceptives.
AB  - Energy, protein, lactose and fat were studied in the milk of mothers who were
      using different types of contraceptives. One hundred and eleven mothers made up
      the following groups. C: control (barrier and natural methods, or sterilization),
      n = 22; combined pill: LDP (low dose pill (levonorgestrel 0.15 mg +
      ethinylestradiol 0.03 mg)), n = 12 and MDP (medium dose pill (levonorgestrel 0.25
      mg + ethinylestradiol 0.05 mg)), n = 13; MP (minipill (norethindrone 0.35 mg)), n
      = 37; DMPA (injectable progesterone (depot medroxiprogesterone acetate 150 mg)),
      n = 17; and IUD (plastic or copper intrauterine device), n = 10. The mean stages
      of lactation were, respectively, 15, 17, 5, 9, 5 and 9 weeks. The mean duration
      of observation for the study groups ranged from 2 to 4 weeks. Milk samples were
      collected before and after initiation of treatment (mean = 20 days; range = 14
      103 days). The stage of lactation and the interval of nursing before sampling
      were recorded so that statistical account could be taken of these uncontrollable
      sources of variability. When incorporated as covariates, they showed that no
      significant differences existed between the groups tested, either before or after
      treatment.

PMID- 1381898
TI  - Intrafamilial transmission of hepatitis C virus (HCV): a major mode of spread in
      the Saudi Arabia population.
AB  - Age-specific prevalence of antibody to hepatitis C virus (anti-HCV) was studied
      in 831 Saudis (441 males, 390 females; 1-53 years old) from Al Baha region, south
      west Saudi Arabia. There was a gradual exposure to HCV early in life with a
      gradual increase with age, reaching a peak of 5.3% in the 30-40 years age group.
      The overall prevalence was 3.6% and 3.1% in males and females, respectively, with
      no statistical difference. Comparison of positivity in family members of seven
      anti-HCV-positive index cases (15/44) with those of five anti-HCV-negative index
      cases (2/44) showed a statistically significant association (chi 2 10.5 with
      Yates' correction). This points to intrafamilial transmission of HCV as a route
      of spread among the Saudi population.

PMID- 1381899
TI  - Seropositivity to hepatitis C virus (HCV) in Saudi children with chronic renal
      failure maintained on haemodialysis.
AB  - Twenty Saudi children (mean age: 7.7 years) with chronic renal failure who had
      received several blood transfusions were screened for antibodies to hepatitis C
      virus (anti-HCV), antibodies to the human immunodeficiency virus (anti-HIV) and
      antibodies to the various markers of hepatitis B virus (HBV). Prevalence of anti
      HCV antibodies was significantly higher in these patients (45%) than in controls
      (1%) (p less than 0.001). In contrast, the exposure rate to HBV was similar in
      both groups (15.0% in patients vs 16.8% in controls). These results underscored
      the high risk of acquiring HCV infection in patients on haemodialysis
      irrespective of age. Currently, practices such as screening blood for HBsAg and
      other preventive measures seem to be effective in controlling HBV but not HCV
      infection in patients on haemodialysis. Perhaps, as with HBV, a stringent policy
      regarding HCV should be implemented if HCV is to be controlled. None of our
      patients or controls was anti-HIV positive.

PMID- 1381900
TI  - Right diaphragmatic eventration simulating neonatal pleural effusion: a case
      report.
AB  - This is a report of a 10-day-old term female infant with right diaphragmatic
      eventration in whom the initial diagnosis was right pleural effusion with
      probable ipsilateral lung hypoplasia. The diagnostic pitfalls in such a case and
      suggestions of how to avoid them are discussed.

PMID- 1381901
TI  - Infected teratodermoid tumour of the mediastinum.
AB  - Teratomas of diverse sites in infants and children have been seen in this
      institution, but this is the first primary germ-cell tumour of the mediastinum in
      a child reported from Northern Nigeria. The patient had an infected teratodermoid
      tumour of the mediastinum which was erroneously diagnosed as chronic empyema
      thoracis.

PMID- 1381902
TI  - Occurrence of chloroquine-induced psychotic manifestations in children with
      malaria.

PMID- 1381903
TI  - Electrocardiographic changes in measles.

PMID- 1381904
TI  - Kawasaki disease in an Egyptian boy.

PMID- 1381905
TI  - Post-translational processing of membrane-associated recombinant human stem cell
      factor expressed in Chinese hamster ovary cells.
AB  - This report describes the structure of soluble human stem cell factor isolated
      from the conditioned medium of Chinese hamster ovary (CHO) cells transfected with
      stem cell factor (SCF) cDNA, which encodes a leader sequence plus 248 additional
      amino acids. The 248 amino acids include a hydrophobic transmembrane region at
      positions 190-212. The isolated material is glycosylated and three bands
      (apparent M(r) 28,000, M(r) 35,000, and M(r) 40,000) are evident by sodium
      dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. After complete
      deglycosylation, the molecular weight by SDS-polyacrylamide gel electrophoresis
      is 18,000-19,000. Structural analyses of the intact SCF, the deglycosylated SCF,
      and a deglycosylated C-terminal peptide were performed by laser desorption, fast
      atom bombardment, or electrospray mass spectrometry. Pulse-labeling of cells with
      35S-labeled Met and Cys resulted in cell-associated glycosylated SCF of M(r)
      33,000-45,000 which was converted to M(r) 33,000 by in vitro treatment with
      glycosidases. During a chase with unlabeled Met and Cys, labeled SCF of M(r)
      28,000, M(r) 35,000, and M(r) 40,000 appeared in the medium; it was converted to
      M(r) 18,000-19,000 by glycosidase treatment. SCF at the surface of the
      transfected CHO cells could be demonstrated by immunofluorescence. The data
      obtained indicate that the recombinant human stem cell factor, as isolated,
      represents proteolytically processed forms containing amino acids 1-165, derived
      from the initially synthesized membrane-bound form of 248 amino acids. Further
      characterization indicated that the M(r) 28,000 form is glycosylated at Asn120,
      the M(r) 35,000 form at Asn120 and Asn65, and the M(r) 40,000 form at Asn120,
      Asn93, and Asn65. Each form also contains O-linked carbohydrate. The N-linked
      glycosylation, particularly that at Asn93 and at Asn65, adversely affects in
      vitro biological activity and receptor binding.

PMID- 1381906
TI  - Species differences and interindividual variation in liver microsomal cytochrome
      P450 2A enzymes: effects on coumarin, dicumarol, and testosterone oxidation.
AB  - Antibody against purified CYP2A1 recognizes two rat liver microsomal P450
      enzymes, CYP2A1 and CYP2A2, that catalyze the 7 alpha- and 15 alpha-hydroxylation
      of testosterone, respectively. In human liver microsomes, this antibody
      recognizes a single protein, namely CYP2A6, which catalyzes the 7-hydroxylation
      of coumarin. To examine species differences in CYP2A function, liver microsomes
      from nine mammalian species (rat, mouse, hamster, rabbit, guinea pig, cat, dog,
      cynomolgus monkey, and human) were tested for their ability to catalyze the 7
      alpha- and 15 alpha-hydroxylation of testosterone and the 7-hydroxylation of
      coumarin. Antibody against rat CYP2A1 recognized one or more proteins in liver
      microsomes from all mammalian species examined. However, liver microsomes from
      cat, dog, cynomolgus monkey, and human catalyzed negligible rates of testosterone
      7 alpha- and/or 15 alpha-hydroxylation, whereas rat and cat liver microsomes
      catalyzed negligible rates of coumarin 7-hydroxylation. Formation of 7
      hydroxycoumarin accounted for a different proportion of the coumarin metabolites
      formed by liver microsomes from each of the various species examined. 7
      Hydroxycoumarin was the major metabolite (greater than 70%) in human and monkey,
      but only a minor metabolite (less than 1%) in rat. The 7-hydroxylation of
      coumarin by human liver microsomes was catalyzed by a single, high-affinity
      enzyme (Km 0.2-0.6 microM), which was markedly inhibited (greater than 95%) by
      antibody against rat CYP2A1. The rate of coumarin 7-hydroxylation varied
      approximately 17-fold among liver microsomes from 22 human subjects. This
      variation was highly correlated (r2 = 0.956) with interindividual differences in
      the levels of CYP2A6, as determined by immunoblotting. These results indicate
      that CYP2A6 is largely or entirely responsible for catalyzing the 7-hydroxylation
      of coumarin in human liver microsomes. Treatment of monkeys with phenobarbital or
      dexamethasone increased coumarin 7-hydroxylase activity, whereas treatment with
      beta-naphthoflavone caused a slight decrease. These results suggest that
      environmental factors can increase or decrease CYP2A expression in cynomolgus
      monkeys, which implies that environmental factors may be responsible for the
      large variation in CYP2A6 levels in humans, although genetic factors may also be
      important. In contrast to rats and mice, the expression of CYP2A enzymes in
      cynomolgus monkeys and humans was not sexually differentiated. Despite their
      structural similarity to coumarin, the anticoagulants dicumarol and warfarin do
      not appear to be substrates for CYP2A6. The overall rate of dicumarol metabolism
      varied approximately 5-fold among the human liver microsomal samples, but this
      variation correlated poorly (r2 = 0.126) with the variation observed in CYP2A6
      levels and coumarin 7-hydroxylase activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1381907
TI  - An O-linked carbohydrate neutralization epitope of HIV-1 gp 120 is expressed by
      HIV-1 env gene recombinant vaccinia virus.
AB  - Previous studies have disagreed about the presence of O-linked carbohydrate
      epitopes on gp 120 of HIV, although antibodies against short-chain O-linked
      glycans neutralize HIV infection and block syncytium formation in vitro. To
      settle this question, we analysed the O-linked glycans of gp 120 by chemical
      methods using purified HIV-1 gp 120 from cells infected with recombinant vaccinia
      virus solely expressing gp 160 or gp 120. Alkaline borohydride degradation of
      recombinant gp 120 released monosaccharides and also slightly larger structures
      (di/trisaccharides) by a beta-elimination, confirming the presence of simple O
      linked oligosaccharides. The functional activity as neutralisation epitopes of
      the O-linked oligosaccharides expressed on recombinant gp 120 was preserved,
      since fusion between uninfected CD4+ cells and cells infected with recombinant
      vaccinia was blocked by monoclonal antibodies to the O-linked oligosaccharides of
      gp 120. Although the mechanism for HIV induction of O-linked oligosaccharide
      neoantigens is unknown, these results indicate that the O-linked neutralization
      epitopes are inherent to the glycoprotein itself, and that the unusual appearance
      of simple O-linked oligosaccharides on gp 120 is independent of any interaction
      between the host cell and retroviral genes other than env.

PMID- 1381909
TI  - Correlation between detection of anti-viral antibody and histopathological
      disease activity in an epidemic of hepatitis C.
AB  - There was an epidemic of non-A non-B hepatitis in a small area of a town in the
      central part of Japan, which began with an outbreak of several patients in 1981
      and then spread extensively with the result that about one third of the
      inhabitants showed abnormality in serum liver function tests at the health check
      performed in 1985. We determined histological diagnoses on that occasion for 167
      individuals of the abnormal population and recently assayed antibodies against
      hepatitis C virus (HCV) for most of their sera left available. Histologically,
      chronic active hepatitis (CAH) was the major pattern, accounting for 59.3% (99
      cases) of the total. Others were chronic persistent hepatitis (CPH) (13.2%),
      chronic lobular hepatitis (CLH) (16.2%), liver cirrhosis (LC) (6.6%) and fatty
      liver (4.8%). In the serological studies, the newly developed system to detect
      antibodies against the viral core protein p 22 was found to be much more
      sensitive than the conventional system to detect anti C 100-3 antibodies. By
      using these two methods in combination, we found that 82% were antibody-positive,
      indicating strong implication of HCV in this epidemic. This was further supported
      by direct detection of the viral genome in patients' sera by polymerase chain
      reaction following reverse transcription. We further found a strong correlation
      between the histological inflammatory activity and the antibody prevalence, since
      nearly all (97.6%) of the CAH cases were antibody-positive by at least either of
      the antibody assays, while only about 50% were positive in the less active cases
      such as CPH and CLH.

PMID- 1381908
TI  - Comparison and fine mapping of both high and low neutralizing monoclonal
      antibodies against the principal neutralization domain of HIV-1.
AB  - Monoclonal antibodies raised against viral lysate of HIV-1 (strain LAV-1) and
      against recombinant gp 160 of HIV-1 (strain HTLV IIIB) which neutralized HIV-1 in
      a type specific manner were mapped with the aid of peptides (Pepscan analysis).
      Each of these monoclonal antibodies bound to peptides located on the principal
      neutralizing domain (PND) of HIV-1. We found that the antigenic sites of the MAbs
      described in this paper are represented by linear peptides of at least 10 amino
      acids long. The affinity of the MAbs is high for these peptides and in the same
      order of magnitude as for native gp 160. The fine mapping of the epitopes may
      reflect structural features of the PND, for instance which amino acid side chains
      are exposed and which are buried in the protein. Furthermore the fine mapping of
      the epitopes explained the HIV type-specific neutralizing activity of the MAbs.
      Antibodies that bound to the tip of the loop (amino acids QRGPGRAF) have a higher
      neutralizing activity than antibodies that bound to amino acids towards the N
      terminal side of the loop (amino acids KSIRI). Furthermore, MAbs that bound to
      virtually the same amino acids on the tip of the loop (amino acids IQRGPGRAF and
      RGPGRAFV) had different neutralizing activities due to different affinities for
      native gp 160. These data reveal that neutralizing activity not only is
      determined by the affinity of an antibody to the neutralizing site but also by
      its fine binding specificities to the V 3 loop of gp 120.

PMID- 1381910
TI  - Characterization of neutralizing antibodies to bovine enterovirus elicited by
      synthetic peptides.
AB  - Six synthetic peptides corresponding to regions of bovine enterovirus (BEV),
      strain VG-5-27, elicited antibodies in mice which reacted with the virus in
      various assays. These antibodies have been characterised on the basis of their
      ability to (1) neutralize the virus, (2) bind to the intact virus particle in an
      immunoprecipitation test, (3) react with the denatured viral proteins, and (4)
      give immunofluorescent staining of virus infected cells. We have also determined
      the proportion of antipeptide antibody which binds to the virus in each case. All
      of the sera immunoprecipitated the virus and neutralized its activity to varying
      extents. Two of the sera specific for VP 1 sequences failed to react with
      denatured VP 1 whereas all the other antisera reacted with their respective
      parental proteins. All of the sera reacted with VG-5-27 infected cells in an
      immunofluorescence test. The proportion of antibodies to each peptide recognizing
      intact virus was variable and did not appear to correlate with neutralizing
      activity. In addition, the ability of each of the sera to react with and
      neutralize three other strains of the virus was analysed. With one of these
      strains significant cross-neutralization was observed.

PMID- 1381911
TI  - Protective role of antigenic sites on the envelope protein of Hantaan virus
      defined by monoclonal antibodies.
AB  - To investigate the role of Hantaan virus envelope glycoprotein in infection, a
      panel of monoclonal antibodies (MAbs) was examined in vitro with several
      serological tests and in vivo by passive transfer experiments in mice. An
      antigenic site, specific for the inhibition of infected cell focus was detected
      with the focus inhibition neutralization test (FINT), in addition to the
      neutralization related antigenic sites, which were revealed by the ordinary focus
      reduction neutralization test (FRNT). Suckling mice were given the MAbs by
      passive transfer followed by lethal Hantaan virus challenge. All neutralizing
      MAbs detected by either FRNT or FINT protected all mice from lethal infection,
      confirming the importance of the antigenic sites as a protective antigen. Mice
      given non-neutralizing MAbs by passive transfer, however, began to die earlier
      than the control group; mean time to death (18.2 +/- 2.1 to 21.5 +/- 2.8 days)
      being significantly shorter than that of the control group (25.8 +/- 1.8, p less
      than 0.01, Mann-Whitney, U probability test). Virus titers in brains of mice
      which died early, were about 10 times higher than those of control mice. These
      results indicated the early death phenomenon of mice which was mediated by the
      anti-virus antibody.

PMID- 1381912
TI  - Immunogenicity of recombinant core particles of hepatitis B virus containing
      epitopes of human immunodeficiency virus 1 core antigen.
AB  - A Gag protein segment of human immunodeficiency virus 1 (HIV-1) has been fused to
      a C terminally truncated core antigen of hepatitis B virus (HBcAg) using an E.
      coli expression system. Fusion of 90 amino acids of HIV-1 Gag protein to HBcAg
      still allowed the formation of capsids presenting on their surface epitopes of
      HIV-1 core protein, whereas fusion of 317, 189, or 100 amino acids of Gag
      prevented self-assembly of chimeric particles. Mice immunized with recombinant
      particles emulsified with Freund's complete adjuvant (CFA) or aluminium hydroxide
      developed high anti-HBcAg titers. However, anti-HIVp24 antibodies were detected
      only in mice inoculated with immunogen emulsified with CFA.

PMID- 1381913
TI  - Characterization and anti-HIV properties of CD 4-coated red blood cells.
AB  - Entry of HIV into its target cells requires its binding to the CD 4 molecule, the
      HIV receptor. Blocking this initial step of HIV life cycle is a potential target
      for the design of anti-HIV drugs. Soluble recombinant CD 4 efficiently blocks HIV
      infection in vitro and is the least toxic anti-HIV drug in humans. However, this
      molecule has a short half-life in vivo, and poorly neutralizes fresh isolates of
      HIV-1. Modifications of soluble CD 4 have been constructed, aimed at increasing
      its half life and other anti-viral properties. We have previously described an
      efficient method to cross-link soluble CD 4 to human red blood cells. We show
      here that these cells are uniformly coated as observed by immunofluorescence
      staining. Each of 8 different anti-CD 4 monoclonal antibodies stained these cells
      indicating that the epitopes recognized by these antibodies are correctly exposed
      at the cell membrane. These CD 4-expressing RBC inhibit specifically and in a
      dose dependent manner the HIV binding to, and infection of, CD 4+ target cells.
      On a CD 4 molar basis, this inhibition is approximately 15 times more efficient
      with CD 4-coated red blood cells than with soluble CD 4.

PMID- 1381915
TI  - [Dependence of keratin No. 17 distribution on the degree of malignancy of bladder
      tumors].
AB  - Keratin No 17 expression (Mab E3) correlated with the stage and degree of
      malignancy of transitional-cell bladder carcinoma (TCC). Antibodies to keratin No
      17 stained only the basal layer of the tumour growth in the TCC I while in TCC II
      III positively stained cells were found everywhere in the tumour and staining was
      diffuse. Immunostaining for the simple keratins No 7, 8, 18, 19 in TCC I-III was
      diffuse. Distribution of keratin No 17 as well as that of the simple keratins was
      not regular in the metaplastic and anaplastic forms of TCC. Thus, the expression
      of keratin No 17 and simple keratins may serve an objective criterion of the
      tumour progression stage.

PMID- 1381914
TI  - Bank vole monoclonal antibodies against Puumala virus envelope glycoproteins:
      identification of epitopes involved in neutralization.
AB  - Bank vole (Clethrionomys glareolus) monoclonal antibodies (MAbs) against the two
      envelope glycoproteins (G 1 and G 2) of the Puumala (PUU) virus were generated
      and characterized. Analyses of the MAbs' antigen and epitope specificities showed
      non-overlapping reactivities of one anti-G 1 and two anti-G 2 MAbs. A significant
      neutralizing activity was shown by the anti-G 1 and one of the anti-G 2 MAbs,
      suggesting the existence of at least one neutralizing domain on each of the two
      glycoproteins. The two neutralizing MAbs reacted with eight PUU-related (serotype
      3) virus strains, but did not react with Hantaan, Seoul, or Prospect Hill viruses
      in an immunofluorescence assay, indicating reactivity with epitopes unique for
      PUU virus. The non-neutralizing anti-G 2 MAb also reacted with Seoul virus,
      revealing the presence of a conserved G 2-epitope common for PUU and Seoul
      viruses, not involved in neutralization. Competitive binding of the MAbs and sera
      from nephropathia epidemica patients indicated that the defined neutralizing and
      non-neutralizing epitopes of the glycoproteins were immunodominant also in
      humans. In another experiment, magnetic beads coated with two MAbs were bound
      with the virus glycoproteins and used for selective enrichment of cells secreting
      anti-glycoprotein antibodies.

PMID- 1381916
TI  - Channel-forming proteins of man and amoebae.

PMID- 1381917
TI  - [Spatial structure and antigenic activity of non-glycosylated forms of embryonal
      prealbumin-1 (EPA-1NG)].
AB  - The influence of temperature and pH on the spatial structure of EPA-1NG has been
      studied by means of circular dichroism and differential UV-spectroscopy,
      indicating the molecule to consist mainly of beta-structures. A conformational
      transition in the molecule was observed within the range of 40-50 degrees C. The
      further temperature elevation (up to 70 degrees C) was accompanied to the
      complete distortion of the parent conformation, which is reversed after cooling
      down to 20 degrees C. A correlation of the spectral data with the antigenic
      activity of genuine EPA-1NG and its carboxymethylated, heat-degraded and pH
      denatured derivatives demonstrates that some antigenic determinants of EPA-1NG
      appear to be topographic.

PMID- 1381918
TI  - [Chemical-enzymatic synthesis and cloning in Escherichia coli of a gene coding
      for human granulocyte-colony stimulating factor].
AB  - Two artificial genes, encoding two forms of human granulocyte colony stimulating
      factor as products of a normal and an alternative splicing, have been by a
      chemical-enzymatic way synthesized and cloned in Escherichia coli. The genes are
      supplied with recognition sites of restriction endonucleases to facilitate the
      further cassette mutagenesis.

PMID- 1381919
TI  - [Gramicidin channels: a new mechanism for transmembrane transfer of ions (from
      high resolution x-ray structural studies of the antibiotic)].
AB  - The crystal structure of the membrane-active antibiotic-cyclopeptide gramicidin S
      complex with urea was determined by the X-ray structure analysis. The gramicidin
      S molecule possesses an antiparallel beta-structure, its slightly twisted 30
      membered cycle has a roughly rectangular form about 4.8 x 13.6 A in size, with
      the lesser side being formed by the main chain atoms of Phe and Pro residues. The
      maximum size of the molecule is 22.9 A. A characteristic feature of the molecule
      is the position of the extended side chains of the Orn residues on one side of
      the molecular cycle in the form of peculiar "legs--tentacles". One of these legs
      is "fastened" by the intramolecular H-bond to O atom of the nearer Phe4 residue,
      the other being free. The distance between the terminal NE atoms of the Orn
      residues is 5.7 A. The side chains of the Phe and Orn2 residues have trans
      orientation, those of the Val, Orn7, Leu residues gauche-orientation. For Val1
      and Leu3 side chains statistical disorder of the terminal C atoms is realized.
      The pyrrolidine rings of the Pro residues adopt Cs-C beta-exo conformation. There
      are one urea and 20 water molecules per one antibiotic molecule in the structure.
      The positions of three water molecules are fully occupied, the others with the
      probability of 0.56-0.20. One of the "water" positions is occupied on 2/3 by
      water, and on 1/3 by the O atom of the alcohol. There is a complicated system of
      intra- and intermolecular H-bonds in the structure, with and without the
      participation of water, alcohol and urea molecules. The gramicidin S molecules,
      collecting around 3(1) axis according to the left-handed double helix, form the
      channels whose outside hydrophobic surface is built of the side uncharged
      radicals, the inside surface being built of the main chain atoms, mainly of the O
      and N atoms and of the ornithine "tails" with uncharged NE atoms at the termini.
      The outer diameter of the channel is 29-43 A, inner (without ornithine "tails")
      is about 12.7 A. At the expense of the change of these "tails" conformation, the
      inner diameter of the channel filled with water molecules may change from 3.4 up
      to 6.3 A. Thus, the ions and particles of a rather large size may pass through
      the channel. The gramicidin channels are discovered and described for the first
      time. The channels in the crystal structure are close-packed under the hexagonal
      law.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1381920
TI  - [Immunochemical study of neurotoxins from Radianthus macrodactylus actinin].
AB  - Polyclonal antibodies to neurotoxin Rm-III from sea anemone Radianthus
      macrodactylus have been obtained. Constants of inhibition of the Rm-III binding
      to its antibodies by the homologous toxins have been determined. Antigenic
      activity of the second type toxins is shown to depend not only on the degree of
      homology but also no the type of substitution in the amino acid sequence. As
      shown by the calculation methods, the antigenic determinants of all the
      homologues have similar positions. Amino acid residues at positions 2, 11, 20,
      28, and 46-48 seem to be included into the antigenic sites of the toxins studied.

PMID- 1381921
TI  - [Immunochemical and functional study of the latrotoxin molecule].
AB  - A panel of monoclonal antibodies (mAb) against alpha-latrotoxin (LT) has been
      produced and their main characteristics have been determined. The influence of
      mAb on the functional effects of LT in synaptosomes from rat brain and on the
      channel formation in bilayer lipid membrane has been investigated. These mAbs do
      not inhibit binding of LT to rat synaptosomes but modify LT-receptor interaction
      in terms of LT's channel-forming and secretogenic effects. Antibodies A6 and A24
      block these effects, whereas A4 partially preserves the secretogenic action of LT
      and completely blocks its channel-forming action. Only antibodies A15 affect the
      LT ability to form cationic channels in BLM, inducing considerable decrease in
      the frequency of the channel formation. These data and their analysis allow to
      identify several functional (and, probably, structural) domains of LT responsible
      for: 1) toxin-receptor interaction; 2) channel-forming and related calcium
      dependent secretogenic effects; 3) calcium-independent secretogenic effects; 4)
      formation of cationic channels in the artificial lipid bilayer.

PMID- 1381923
TI  - Effects of chronic bupropion on interstitial concentrations of dopamine in rat
      nucleus accumbens and striatum.
AB  - Bupropion is a novel atypical antidepressant that inhibits dopamine (DA) uptake.
      The present experiments investigated the effects of acute (10 mg/kg, twice daily
      for 2 days) and chronic (10 mg/kg, twice daily for 21 days) bupropion treatment
      on interstitial DA concentrations using simultaneous in vivo microdialysis in the
      nucleus accumbens (NAC) and striatum of awake freely moving rats. Compared to
      animals that had not previously been exposed to the drug, bupropion (25 mg/kg,
      IP) induced increases in extracellular DA were significantly enhanced in the NAC
      of the chronic but not the acute bupropion group. This effect was regionally
      selective, as it was not observed in the striatum. In accordance with previous
      reports, concurrent behavioral measurements indicated that the locomotor
      stimulant effects of bupropion were also enhanced in the chronic group. These
      results demonstrate that bupropion-induced behavioral sensitization is
      accompanied by a selective potentiation of the effects of this compound on
      interstitial DA concentrations in the NAC.

PMID- 1381922
TI  - [Structure of the O-specific polysaccharide of Vibrio fluvialis serovar 3].
AB  - O-Specific polysaccharide composed of L-rhamnose and 2-acetamido-2-deoxy-D
      mannose was obtained on mild acid degradation of the V. fluvialis
      lipopolysaccharide. On the basis of the 13C-NMR data and methylation studies, the
      following structure was suggested for the polysaccharide repeating unit: ----4)
      alpha-L-Rhap-(1----3)-beta-D-ManpNAc-(1---- This structure was confirmed by
      calculations using known glycosidation effects on 13C chemical shifts.

PMID- 1381925
TI  - Inhibitory effects of azelastine on nasal allergic responses in sensitized guinea
      pigs.
AB  - The in vivo effects of the antiallergic drug azelastine were investigated in
      sensitized guinea pigs. Topical administration of antigen into the nasal cavity
      produced an increase in nasal vascular permeability together with an increase in
      both the histamine and leukotriene C4 (LTC4) concentrations of nasal lavage
      fluid. Pre-treatment with azelastine significantly inhibited both the LTC4
      release and the increase in nasal vascular permeability. These results suggest
      that azelastine inhibits the release of antigen-induced leukotrienes and
      increases nasal vascular permeability in vivo.

PMID- 1381926
TI  - A functional view of the entrances of L-type Ca2+ channels: estimates of the size
      and surface potential at the pore mouths.
AB  - At extreme membrane potentials, the unitary inward and outward currents through L
      type Ca2+ channels become diffusion controlled and saturate. The magnitudes of
      these currents indicate that the pore entrances are asymmetric, with the external
      mouth being much larger than the internal one. On the other hand, negative
      surface potentials at the two ends of the pore are rather similar. Both would be
      significant only when the ambient ionic strength is 110 mM or less. We conclude
      that the surface charges will not help much in concentrating the channel's
      favorite divalent cations in the physiological condition. However, the pore does
      possess an external mouth large enough to make the important inward Ca2+ flow not
      limited by diffusion, even with only 1 mM external Ca2+.

PMID- 1381924
TI  - Structure and dynamics of ligand-template interactions of topoisomerase
      inhibitory analogs of Hoechst 33258: high field 1H-NMR and restrained molecular
      mechanics studies.
AB  - The binding characteristics of Hoechst 33258 (1), a synthetic bis-benzimidazole,
      and its structural analog 2, with one of the benzimidazoles replaced by a
      pyridoimidazole, to the self-complementary decadeoxyribonucleotide sequences
      d(CGCAATTGCG)2 (A) and d-(CATGGCCATG)2 (B) respectively, were examined using high
      field 1H-NMR techniques. Selective complexation induced chemical shift changes,
      the presence of exchange signals and intermolecular NOE contacts between the
      ligands and the minor groove protons of the oligonucleotides suggest the
      preferred binding sites as the centrally located AATT segment for complex A1, and
      the CCAT segment for complex B2. The B-type conformations of the two DNA duplexes
      are preserved upon complexation, as confirmed by the 2D-NOESY based sequential
      connectivities involving DNA base and sugar protons. Close intermolecular NOE
      based contacts between the ligands and their respective DNA sequences were
      further refined to model the ligand-DNA complexes starting from the computer
      generated B-type structures for the oligonucleotides. Force field calculations of
      ligand-DNA interaction energies indicate a more favorable contribution from the
      van der Waals energy component in the case of complex A1 consistent with its
      stronger net binding compared with the complex B2. Overall, the incorporation of
      a pyridinic nitrogen in Hoechst 33258 structure alters its selectivity for base
      pair recognition from A.T to G.C, resulting largely from the formation of a
      hydrogen bond between the new basic center and the 2-NH2 group of a guanosine
      moiety. The rates for the exchange of ligands between the two equivalent binding
      sites (AATT for 1, and CCAT for 2) of the self-complementary DNA sequences, are
      estimated from analyses of coalescence of NMR signals to be 189s-1 at 301 K for
      A1 and 79s-1 at 297 K for B2; which correspond to delta G++ of 13.8 and 18.6
      kcal.mol-1 respectively.

PMID- 1381927
TI  - Palliation of malignant phaeochromocytoma with combination chemotherapy.

PMID- 1381928
TI  - Induction of resistance to 6-thioguanine and cytarabine by a range of anticancer
      drugs in Chinese hamster AA8 cells.
AB  - A mutagenicity assay using AA8 Chinese hamster cells has been used to explore the
      potential of some currently used clinical anticancer drugs to induce cells
      resistant to 6-thioguanine and cytarabine. Preliminary experiments gave evidence
      of a "low dose" and "high dose" resistance to cytarabine, and subsequent work
      considered only the latter of these events. When ethyl methane sulphonate was
      used as a reference mutagen, induced resistance to cytarabine developed
      substantially later and at a lower frequency than resistance to 6-thioguanine. Of
      the clinical drugs tested, carmustine showed the highest ability to induce either
      6-thioguanine or cytarabine resistant cells. Bleomycin, daunomycin and amsacrine
      showed moderate ability, while vincristine was essentially inactive in these
      assays. Such information could potentially be used in selecting new drug
      combinations or timing of drug administration in cancer chemotherapy.

PMID- 1381929
TI  - Does extragonadal presentation impart a worse prognosis to abdominal germ-cell
      tumours?
AB  - The prognostic significance of extragonadal rather than gonadal presentation of
      germ-cell tumour in 51 patients presenting between 1979 and 1988 with abdominal
      tumours was compared with that of 51 control patients with testicular primary
      tumours matched for bulk fo disease, serum tumour marker concentration, age and
      year of treatment. Very large volume tumour was found at initial staging in 24
      extra-gonadal cases (47%) and high tumour markers in 29 (57%). Actuarial survival
      at 2 and 5 years was 82% and 70% for cases and 78% and 63%, respectively, for
      controls. These outcomes were not significantly different and the relative hazard
      of death for cases compared with controls was 0.7 (95% confidence intervals 0.3
      1.5). Thus the presentation of germ-cell tumours with a retroperitoneal mass does
      not itself adversely influence prognosis compared with testicular presentation
      with equivalent disease extent. However it is rare for extragonadal presentation
      to be associated with small volume disease.

PMID- 1381930
TI  - Neuroendocrine and epithelial markers in diagnostic bronchial lung cancer biopsy
      specimens.
AB  - The incidence of neuroendocrine and epithelial markers was investigated by
      immunocytochemistry in archival, lung cancer, bronchial biopsy specimens (n =
      48). No correlation of antigenicity with histological type was observed. 79% non
      small cell lung carcinoma (NSCLC) and 61% small cell lung carcinoma (SCLC) were
      positive for epithelial markers. HuTu-m3 did not discriminate adenocarcinomas and
      squamous cell carcinomas from SCLC. 83% SCLC and 93% NSCLC were positive for one
      or more neuroendocrine marker. Multiple neuroendocrine markers were found in 61%
      SCLC, 83% NSCLC and 83% squamous cell carcinomas, this incidence being greater in
      the NSCLC group, and in the squamous carcinomas in particular, than previously
      reported.

PMID- 1381931
TI  - [Differential diagnosis of thalassemia syndromes].
AB  - In Sardinia, as in other areas with a high incidence of thalassemia syndromes, a
      prevention program based on the detection of healthy carriers through mass
      screening and on prenatal diagnosis in the at-risk couples has been in course for
      several years. The commonly adopted beta-thalassemia flow-chart consists of a
      first operative step involving simple and widely standardized tests: the
      estimation of red cell indices, the measurement of Hb A2 and Hb electrophoresis.
      These investigations permit the identification of the majority of the at-risk
      couples for beta-thalassemia. However, the not infrequent evidence of Hb A2
      borderline levels, with or without microcytosis, isolated microcytosis or Hb F
      increased values, causes some problems in differential diagnosis, because these
      findings can indicate the presence of silent beta-thalassemic traits or other
      beta-thalassemic like states. A diagnostic definition of these unusual
      hematological phenotypes is particularly important for the identification of
      eventual at-risk couples. In this paper we report our data concerning the
      voluntary screening for beta-thalassemia carried out in North Sardinia. The
      operative flow-chart is shown. In a population with a high incidence of
      phenotypically heterogeneous thalassemic syndromes, such as that of Sardinia,
      differential diagnosis of thalassemic traits can require molecular studies. This
      molecular characterization, which could be carried out in specialized reference
      centers, is today absolutely necessary both for exact identification of at-risk
      couples and eventual prenatal diagnosis.

PMID- 1381932
TI  - The effect of dietary copper on rat plasma apolipoprotein B, E plasma levels, and
      apolipoprotein gene expression in liver and intestine.
AB  - The plasma levels of apo B and apo E, and the level of hepatic and intestinal
      mRNA coding for these apolipoproteins were investigated in weanling male rats
      pair-fed for 6 wk with a control or copper-deficient diet. Plasma cholesterol,
      triglycerides, and phospholipids were significantly increased, and plasma apo B
      and apo E levels were also markedly increased in copper-deficient rats as
      compared to control rats. Copper deficiency significantly increased triglyceride
      levels and decreased cholesterol levels in the liver. No major differences in the
      levels of hepatic and intestinal apo B and apo E mRNA occurred between control
      and copper-deficient rats. These data imply that hypertriglyceridemia dn
      hypercholesterolemia owing to the copper deficiency are not accompanied by
      modifications in the gene expression at the mRNA level in the liver and intestine
      of the apolipoproteins studied.

PMID- 1381933
TI  - Disturbances in heme biosynthesis in rabbits after administration per os of low
      doses of tin or lead.
AB  - The experiment was performed on female rabbits that received per os equimolar
      doses (17 microM Me/kg) of SnCl2 x 2 H2O or Pb (CH3 COO)2 every day for 5 d. The
      activity of delta-aminolevulinic acid dehydratase (ALA-D) in the whole blood,
      liver, kidneys, brain, spleen, and bone marrow, concentration of free erythrocyte
      protoporphyrins (FEP), activity of delta-aminolevulinic acid synthetase (ALA-S)
      in the liver and bone marrow, urine delta-aminolevulinic acid (ALA-U), and
      coproporphyrins (CP-U) were determined. Lead and tin concentrations in the blood
      were estimated. Lead caused a significant inhibition of ALA-D in the blood,
      increased FEP concentration, and ALA and CP excretion in urine of rabbits. Lead
      also decreased ALA-D activity in the bone marrow and in the liver, and did not
      change ALA-S activity in the liver and bone marrow. Tin did not change any of the
      examined indices. Tin doses applied in the present study, maintained within the
      limits of permissible standards of metal levels in human diet, did not affect the
      process of heme biosynthesis in rabbits.

PMID- 1381935
TI  - A comparative study in rats of measures of the availability of dietary zinc and
      iron.
AB  - The purpose of this study was to compare three measures of the availability of
      dietary Zn and Fe in order to test their validity. Thirty-six 5-wk-old rats were
      fed deionized water and wheat crispbread made from endosperm flour, whole-grain
      flour, or endosperm flour supplemented with Zn and Fe to the whole-grain levels
      ad libitum for 14 d. The retention of 65Zn and 59Fe from test meals of the same
      breads after 1 wk and the sum of the excretion of endogenous Zn and Fe (injected
      65Zn and 59Fe) with the Zn and Fe balances, respectively, were used as
      independent measures of Zn and Fe absorption. Measurements of Zn absorption, Zn
      balance, and serum Zn concentration gave quite different results with regard to
      the availability of Zn in the three breads, presumably because of the homeostatic
      regulation of the absorption and excretion of Zn when the Zn in the diet is in
      excess of the body's needs. Measurements of Fe absorption, Fe balance, and Fe
      concentrations in liver and serum were consistent in demonstrating overloading of
      Fe in the group given wheat-endosperm crispbread supplemented with Zn and Fe, but
      there was evidence that the isotope retention method overestimated iron
      absorption.

PMID- 1381936
TI  - Lithium in scalp hair of adults, students, and violent criminals. Effects of
      supplementation and evidence for interactions of lithium with vitamin B12 and
      with other trace elements.
AB  - The lithium content of human hair shows an approximately linear response to
      extradietary lithium supplementation at dosage levels of up to 2000 micrograms/d.
      From the mean hair lithium concentration of 0.063 micrograms/g in 2648
      predominantly American adults, and the reference hair lithium concentrations
      determined in the present study, the mean lithium intakes were calculated to be
      730 micrograms/d. Hair lithium concentrations were extremely low in nearly 20% of
      the American samples, and in samples collected in Munich, Germany and Vienna,
      Austria. Hair lithium levels are low in certain pathological conditions, e.g.,
      heart disease, in learning-disabled subjects, and in incarcerated violent
      criminals. The highest levels were observed in samples of a lithium-treated
      psychiatric patient. A statistically highly significant direct association was
      observed between the hair lithium and cobalt concentrations, which suggests a
      role of lithium in the transport and distribution of vitamin B12. Interactions of
      lithium with other trace elements are also discussed.

PMID- 1381934
TI  - Roles of iron in neoplasia. Promotion, prevention, and therapy.
AB  - Research and clinical observations during the past six decades have shown that:
      1. Iron promotes cancer cell growth; 2. Hosts attempt to withhold or withdraw
      iron from cancer cells; and 3. Iron is a factor in prevention and in therapy of
      neoplastic disease. Although normal and neoplastic cells have similar qualitative
      requirements for iron, the neoplastic cells have more flexibility in acquisition
      of the metal. Excessive iron levels in animals and humans are associated with
      enhanced neoplastic cell growth. In invaded hosts, cytokine-activated macrophages
      increase intracellular ferritin retention of the metal, scavenge iron in areas of
      tumor growth, and secrete reactive nitrogen intermediates to effect efflux of
      nonheme iron from tumor cells. Procedures associated with lowering host intake of
      excess iron can assist in prevention and in management of neoplastic disease.
      Chemical methods for prevention of iron assimilation by neoplastic cells are
      being developed in experimental and clinical protocols. The antineoplastic
      activity of a considerable variety of chemicals, as well as of radiation, is
      modulated by iron. The present article focuses on recent findings and suggests
      directions for further cancer-iron research.

PMID- 1381937
TI  - Copper organo-chelators in Aspergillus fumigatus and Penicillium chrysogenum.
AB  - The presence of copper in the growth medium induces the biosynthesis of several
      low-mol-wt copper ogano-chelators in Aspergillus fumigatus and Penicillium
      chrysogenum. By use of P. chrysogenum, we were able to prepare several low-mol-wt
      metallothionein chelators, as well as several short-chain copper chelatins. The
      amino acid composition of a chelatin of mol wt approx 799 Da revealed the
      presence of cysteine, glutamic acid, glycine, and leucine. Use of A. fumigatus
      led to fewer copper chelators and one very short-chain peptide: a chelatin of mol
      wt approx 624 Da. composed of four amino acids, asparagine, glutamic acid,
      cysteine, and glycine. These results may confirm our assumption that fungi
      detoxify the deleterious action of toxic elements by producing high levels of
      heavy metal chelators/chelatins.

PMID- 1381938
TI  - Silicon metabolism. The interrelations of inorganic silicon (Si) with systemic
      iron (Fe), Zinc (Zn), and copper (Cu) pools in the rat.
AB  - The influence of silicon treatment on the levels of trace elements zinc (Zn),
      copper (Cu), and iron (Fe) in serum and tissues was studied in rats. The
      concentrations of silicon, iron, and zinc were estimated in samples of sera and
      tissues of rats receiving per os a soluble, inorganic silicon compound--sodium
      metasilicate nonahydrate (Na2SiO3.9H2O), dissolved in the drinking water. An
      increase of copper concentrations in liver and aortic walls in the experimental
      group was observed, with simultaneous reduction of zinc amounts in serum and all
      the tissue samples in the course of the experiment. The iron concentrations in
      the analyzed samples did not show any significant changes between both groups.
      The silicon levels in serum and in all the examined tissues were significantly
      higher in the tested group. The results provide evidence for the silicon
      interaction with copper and zinc, which could result in a number of metabolic
      process modifications, antiatheromatous activity among them.

PMID- 1381939
TI  - Indices of iron and copper status during experimentally induced, marginal zinc
      deficiency in humans.
AB  - This study examined the effect of diet-induced, marginal zinc deficiency for 7
      wks in 15 men (aged 25.3 +/- 3.3 yrs; mean +/- SD) on selected indices of iron
      and copper status. The regimen involved low-zinc diets based on egg albumin and
      soy protein with added phytate and calcium such that mean [phytate]/[Zn] and
      [phytate] X [Ca]/[Zn] molar ratios were 209 and 4116, respectively, for 1 wk,
      followed by 70 and 2000, respectively, for 6 wks. Subjects were then repleted
      with 30 mg Zn/d for 2 wks. Plasma copper, Cu,Zn-superoxide dismutase (Cu,Zn-SOD)
      activity in plasma and red blood cells (RBC), hemoglobin, hematocrit, and serum
      ferritin were determined weekly on fasting blood samples. Significant reductions
      (p less than 0.05) after 7 wks in RBC Cu,Zn-superoxide dismutase (49.5 +/- 7.2 vs
      33.6 +/- 6.3 U/mg Hb) and serum ferritin (69.2 +/- 38.7 vs 53.8 +/- 33.7
      micrograms/L) occurred; no comparable decline was noted for plasma Cu,
      hemoglobin, or hematocrit. Significant (p less than 0.05) but less consistent
      changes were also observed in plasma superoxide dismutase activity. None of the
      changes were associated with the decreases in plasma, urinary and hair zinc
      concentrations, and alkaline phosphatase activity in RBC membranes. Results
      indicate that the biochemical iron and copper status of the subjects was
      marginally impaired, probably from the dietary regimen that induced marginal zinc
      deficiency.

PMID- 1381940
TI  - Transient encephalopathy following a single exposure of high-dose methotrexate in
      a child with acute lymphoblastic leukemia.
AB  - An episode of transient encephalopathy after the first course of intravenous high
      dose methotrexate (HD-MTX; 1000 mg/m2) was observed in a 4-year-old girl with
      acute lymphoblastic leukemia. The neurological abnormalities took place 5 days
      after HD-MTX therapy. She experienced complex partial seizure and left
      hemiparesis, which resolved spontaneously in 5 days. Cranial computed tomographic
      scan and magnetic resonance imaging showed multiple low-density lesions in
      bilateral hemispheres. It is well appreciated that neurotoxicity from MTX follows
      prolonged exposures, often accompanying or following radiation therapy. To our
      knowledge, however, there have been no reports that such neurological
      complications developed following a single exposure of HD-MTX in patients with
      ALL. Follow-up electroencephalograms showed that she had periodic lateralized
      epileptiform discharges (PLEDS), suggesting functional deafferentation of
      cortical neurons following HD-MTX. Moreover, the serum and CSF MTX levels
      following a second low-dose course and her clinical course suggested that she had
      presumably central nervous system leukemia at the time of HD-MTX therapy, which
      might have been related to neurological complications. The pathogenesis of MTX
      induced neurotoxicity is discussed.

PMID- 1381942
TI  - Cellular and molecular aspects of mouse primordial germ cell migration and
      proliferation in culture.
AB  - The development of mouse primordial germ cells is followed from their first
      appearance in the extraembryonic mesoderm of the posterior amniotic fold (7 dpc
      embryo) to their settlement in the genital ridges (12.5 dpc embryo). The role of
      fibronectin as adhesive substrate and/or in stimulating cell motility during PGC
      migration is discussed. Recent papers showing how PGCs migrate when cultured in
      vitro on cellular monolayers are reviewed. The process of PGC homing is proposed
      to be controlled by chemotaxis as well by developmentally regulated cell-to-cell
      interactions. Finally, evidence that survival and proliferation of PGCs is
      strictly dependent on growth factors such as LIF and MGF, and possibly on a cAMP
      dependent mechanism is reported.

PMID- 1381941
TI  - Treatment of chemotherapy-induced neutropenia in children with subcutaneously
      administered recombinant human granulocyte colony-stimulating factor.
AB  - Fifty-six children with various malignancies were treated subcutaneously with
      recombinant human granulocyte colony-stimulating factor (rhG-CSF, KRN 8601) for
      neutropenia induced by cancer chemotherapy. Patients received the first
      chemotherapy without rhG-CSF (control course). In the second course, rhG-CSF was
      given once daily, starting 3 days after completion of identical chemotherapy (day
      3) and continuing until day 12. At day 12, the white blood counts and neutrophil
      counts were found to be 6.8 and 30 times higher in the rhG-CSF course than in the
      control course (P = .0001) Nadirs of white blood counts and neutrophils were
      significantly elevated in the rhG-CSF course (P = .003 and .0001, respectively).
      rhG-CSF administration shortened the neutropenic period in the majority of
      patients. Children tolerated the rhG-CSF administration well and we have hereby
      confirmed that rhG-CSF administration is useful for proceeding with chemotherapy
      in children with cancer.

PMID- 1381943
TI  - The development of normal and ectopic sensilla in the wings of hairy and Hairy
      wing mutants of Drosophila.
AB  - We have utilized enhancer trap markers to follow the development of ectopic
      sensillar precursors in the wings of Drosophila induced by the mutations hairy
      and Hairy wing. Normal sensilla are still present in these mutations, and can be
      distinguished from ectopic sensilla based upon both the position and the timing
      of their development. This correlates well with the development of ectopic
      achaete expression in these mutations: such staining is detected only after the
      appearance of normal staining. Thus, neither mutation appears to alter the
      specification of proneural clusters in the wing, as identified with anti-achaete,
      or the specification of sensillar precursors within these clusters. Rather, both
      act to induce the formation of a temporally and spatially distinct phase of
      sensillar development.

PMID- 1381944
TI  - Diminution of antibodies directed against tumor cell surface epitopes: a single
      chain Fv fusion molecule specifically recognizes the extracellular domain of the
      c-erbB-2 receptor.
AB  - We are evaluating strategies for the inhibition of growth or the selective
      killing of tumor cells. Cell surface antigens which are exclusively expressed or
      which are enhanced in their expression in tumor cells might provide the means to
      target cytotoxic or cytostatic agents to these cells. Few tumor specific cell
      surface antigens have been found, but the enhanced expression of growth factor
      receptors has been described for several types of tumors. A prominent example is
      the overexpression of the c-erbB-2 receptor in a high percentage of primary
      breast and ovarian carcinomas. We have derived monoclonal antibodies against the
      extracellular domain of the c-erbB-2 receptor. The antibody molecules were
      genetically engineered to minimize their size and to allow for their functional
      modification. For this purpose the cDNA sequences corresponding to the variable
      domains of one monoclonal antibody (FRP5) were molecularly cloned and joined by a
      short linker. The resulting single chain antibody molecule (scFv) was expressed
      in bacteria and purified. We show in an immunoprecipitation experiment that this
      molecule retains its ability to recognize the c-erbB-2 extracellular domain. This
      molecule could become a valuable vehicle to specifically transport anti-tumor
      agents to breast cancer cells.

PMID- 1381945
TI  - Molecular analysis of a partial deletion of 22q in a central nervous system
      rhabdoid tumor.
AB  - We previously reported the non-random occurrence of monosomy 22 in rhabdoid or
      atypical teratoid tumors of the brain in three young children. We now present
      cytogenetic and molecular studies of an additional rhabdoid tumor with the
      karyotype 46,XX,-9,-22,+i(1q),+der(22)t(9;22)(p13;q11)/45,XX,-9,-10,-
      22,+i(1q),+der(22)t(9;22)(p13;q11). These studies further demonstrate the
      involvement of chromosome 22, and they begin to define the critical region
      containing a gene or genes involved in the development or progression of rhabdoid
      tumors of the brain.

PMID- 1381946
TI  - Detection of RAS mutations in archival testicular germ cell tumors by polymerase
      chain reaction and oligonucleotide hybridization.
AB  - Preliminary studies of RAS mutational activation in human testicular germ cell
      neoplasms have yielded conflicting results. Whereas two studies of clinical
      material revealed a significant incidence of N- and KRAS mutations, two studies
      of a variety of germ cell lines failed to document RAS mutations. To clarify the
      incidence of RAS mutations in these tumors, we studied archival paraffin
      embedded, formalin-fixed orchiectomy specimens from 25 nonseminomas (NSGCT), 18
      seminomas (SEM), and one Leydig cell tumor. For 14 of the 44 neoplasms, DNA was
      also available from nonmalignant testis adjacent to the tumor. Six age-matched
      patients had testes removed because of nonmalignant disease and were studied as
      controls. Polymerase chain reaction (PCR) amplified the K-, N-, and HRAS 12, 13,
      and 61 codons of these specimens, and mutations were detected with mutation
      specific oligonucleotide probe hybridization of Southern and slot blots. Four
      mutations were found in KRAS 12 (4/44;[9.1%]). One seminoma [1/18(5.6%)]
      contained the mutation GGT(GLY)----CGT(ARG), and three NSGCT [3/25(12%)] were
      found to have GGT(GLY)----GAT(ASP) mutations. One of the NSGCT mutations was
      detected in adjacent nonmalignant tissue, but the corresponding tumor did not
      contain any detectable mutation. No mutations were detected at KRAS 13 or 61, in
      NRAS or HRAS 12, 13, or 61, or in the control normal testes. PCR, slot blots, and
      hybridizations were performed twice by two separate investigators for
      confirmation of results. PCR-generated mutation-specific positive controls were
      created for all possible RAS mutations, and these along with wild-type DNA
      controls were integral to interpretation of the oligonucleotide mismatch
      hybridization assay. By using positive and negative controls, we have detected a
      relatively low incidence of RAS mutations in archival human testicular germ cell
      tumors.

PMID- 1381947
TI  - Molecular characterization of a large homozygous deletion in the small cell lung
      cancer cell line U2020: a strategy for cloning the putative tumor suppressor
      gene.
AB  - Homozygous deletions are instrumental in the detection and cloning of tumor
      suppressor genes. We report the isolation and characterization of 39 new single
      copy probes saturating a submicroscopic homozygous deletion detected in the DNA
      of the small cell lung cancer (SCLC) cell line U2020. The probes were selected
      from a large collection, covering the entire length of chromosome 3 with an
      estimated average spacing of 100-150 kb. Based on the number of probes in the
      deletion and the probe density, the size of the U2020 submicroscopic deletion was
      estimated to be in the range of 4-7 megabases. Among the deleted loci, 17 showed
      conservation across species, probably representing potential coding gene
      sequences. By genetic and physical mapping of a large randomly chosen fraction of
      the deleted probes, we defined the location of the U2020 deletion within
      chromosome band 3p12. Our cloning strategy is based on narrowing the region of
      interest by eliminating probes that retain heterozygosity in SCLC samples, thus
      selecting for probes in the region of common loss.

PMID- 1381948
TI  - Identification of a whole-arm translocation by in situ hybridization with
      directly fluorochrome-labeled probes in a myelodysplastic syndrome.
AB  - A case of myelodysplasia was found to have a complex bone marrow karyotype,
      involving an apparent whole-arm translocation between 17q and 18q. The
      application of a simplified fluorescence in situ hybridization technique, using
      directly fluorochrome-labeled centromere-specific alpha-satellite DNA probes,
      demonstrated the presence of sequences from both chromosomes 17 and 18 in the
      centromere of the derivative chromosome. This proves that a true whole-arm
      translocation had occurred. The case exemplifies how in situ hybridization
      analysis can be used to resolve interpretation problems in cancer cytogenetics.

PMID- 1381949
TI  - Wilms' tumor-specific methylation pattern in 11p13 detected by PFGE.
AB  - The analysis of 2,550 kb from 11p13 in Wilms' tumor (WT) material revealed two
      regions that differed significantly in their methylation between tumor and normal
      tissue. In WT a hypomethylated area defined by an NruI and MluI recognition site
      100-150 kb centromeric of the WT gene WT1 (site A) and hypermethylation defined
      by an NruI and SacII site 100 kb telomeric of the WT1 gene were found (site B).
      The degree of methylation in region B varied between 20 and 100% in the different
      samples; the highest level was observed in tumors without preoperative
      chemotherapy. The CpG island 5' of the WT1 gene was partially methylated in 2/29
      tumors analyzed. The methylation state of regions A and B could reflect the
      normal pattern present in a subset of embryonal kidney cells, from which WT
      develops.

PMID- 1381950
TI  - Clinical impact of chromosome 1 aberrations in neuroblastoma: a metaphase and
      interphase cytogenetic study.
AB  - Neuroblastoma tumors are characterized by aberrations of chromosome 1. Rapid
      detection of these chromosomal aberrations at diagnosis could give important
      clues to outcome and therapy. We attempted to detect numerical and structural
      aberrations of chromosome 1 not only by classical metaphase cytogenetics but also
      by interphase cytogenetics in order to overcome difficulties of karyotyping due
      to diminished metaphase quality and quantity in primary neuroblastoma samples.
      Karyotypic changes of chromosome 1 in 53 primary neuroblastomas were evaluated.
      In addition, we successfully performed interphase cytogenetics using single and
      double in situ hybridization procedures with chromosome 1-specific repetitive DNA
      probes on nuclei preparations obtained from 46 and 20 tumors, respectively.
      Polysomies of structurally normal chromosomes 1 were predominantly seen in tumors
      with good prognosis, whereas deletions of 1p material were nearly exclusively
      confined to progressive tumors. Numerical and structural chromosome 1 aberrations
      as studied by metaphase and interphase cytogenetics are thus valuable prognostic
      markers in neuroblastoma.

PMID- 1381951
TI  - Viral integration and fragile sites in human papillomavirus-immortalized human
      keratinocyte cell lines.
AB  - Human papillomavirus (HPV) types 16 and 18 integration sites were mapped in six
      HPV-immortalized human keratinocyte cell lines by fluorescence in situ
      hybridization (FISH). Mapping of HPV sequences in these cell lines revealed that
      HPV integration varied in copy number and location but that integration sites
      were stable over extended passages in culture. Integration occurred at different
      sites throughout the genome and did not correspond to the location of specific
      cellular genes. However, integration sites were consistent with integration near
      or within known fragile sites in five of the six cell lines. Induction of
      aphidicolin-sensitive fragile sites in one cell line prior to in situ
      hybridization revealed that integrated HPV DNA was disrupted by fragile-site
      expression, suggesting that integration occurred within a fragile site.

PMID- 1381952
TI  - Translocation t(11;14)(q13;q32) in chronic lymphoid disorders.
AB  - The translocation t(11;14)(q13;q32) has been described in a spectrum of B
      lymphoproliferative diseases and involves a putative oncogene, BCL1, which maps
      to chromosome band 11q13. Recent evidence indicates that this abnormality may
      delineate particular subtypes of lymphoma, such as intermediate lymphocytic and
      centrocytic lymphomas. Thus the possible significance of the t(11;14) within B
      cell disorders should be reexamined in the light of a more objective approach to
      classifying these diseases by morphology, histology, and immunophenotype. We
      describe 16 patients with t(11;14)(q13;q32) from a series of 90 patients with
      chronic lymphoid disorders in whom clonal chromosome abnormalities were detected.
      All the cases were leukemic: prolymphocytic (B-PLL; 4/15 cases), chronic
      lymphocytic leukemia (CLL) with increase in prolymphocytes (2/9 cases), or non
      Hodgkin lymphoma in leukemic phase, intermediate (3/4 cases), lymphoplasmacytic
      (2/2 cases), splenic lymphoma with villous lymphocytes (4/18 cases), and
      follicular (1 case). None of the CLL (25) or hairy cell leukemia cases (15) had
      t(11;14). Our findings showed that t(11;14) occurred in leukemias of mature B
      cells with lymphoplasmacytic features as judged by morphology and
      immunophenotype.

PMID- 1381953
TI  - Molecular analysis of 12 patients with the t(8;21) translocation and M2 acute
      myelogenous leukemia.
AB  - The t(8;21)(q22;q22) is a nonrandom cytogenetic abnormality associated with acute
      myelogenous leukemia of the M2 subtype (FAB classification). The 8q- and 21q+
      derivative chromosomes have previously been isolated in somatic cell hybrids and
      used to map the anonymous sequences D21S65 and D21S17, which were proximal and
      distal, respectively, to the breakpoint on chromosome 21. DNA from a series of 12
      t(8;21) patients and 7 controls was analyzed by pulsed field gel electrophoresis.
      Physical linkage of probes D21S65 and D21S17 on a 2100 kb NruI fragment was
      established by partial digestion experiments. In all the patients, the
      translocation generated a rearranged D21S65 NruI fragment of 650 to 750 kb,
      suggesting heterogeneity in the breakpoints. This heterogeneity was confirmed by
      using BssHII, SacII, and EagI enzymes. Our results are consistent with the
      presence of a 100 Kb breakpoint cluster region on chromosome 21 encompassing the
      AML1 gene. Interestingly, in half of the patients, demethylation of an NruI site
      located 7 kb proximal to the last exon of the AML1 gene occurred on the
      nontranslocated chromosome 21.

PMID- 1381954
TI  - Chromosome changes in a case of hibernoma.
AB  - Cytogenetic analysis of a rare adipose tissue tumor, hibernoma, a benign
      proliferation of the brown fat, is presented for the first time. A complex
      translocation involving bands 1p36, 2q33, 5q22, and 11q13 was found as the sole
      chromosome abnormality.

PMID- 1381956
TI  - Translocation (12;22)(q13-14;q12) is a nonrandom aberration in soft-tissue clear
      cell sarcoma.

PMID- 1381957
TI  - No alterations in exon 21 of the RB1 gene in sarcomas and carcinomas of the
      breast, colon, and lung.
AB  - Studies of mutant genotypes of the retinoblastoma susceptibility gene (RB1) in
      different solid tumors have mainly been concentrated on the demonstration of loss
      of heterozygosity (LOH) at both internal and external polymorphic sites. One
      reason for this is the complex organization of the gene. The p105RB protein has
      been shown to interact with both DNA and regulatory cellular proteins and
      oncoproteins. The amino acids encoded by exon 21 are implicated in several of
      these interactions. Both point mutations and intragenic deletions involving exon
      21 have previously been reported in human tumors. We have examined RB1 exon 21
      from a number of human tumor types where significant LOH in or around the RB1
      gene has been reported. DNA from 78 primary tumors was amplified using the
      polymerase chain reaction (PCR) with primers covering exon 21, followed by
      constant denaturant gel electrophoresis (CDGE). The 78 tumors included 11 breast
      carcinomas, 30 nonsmall cell lung carcinomas, 6 colon carcinomas, and 31
      sarcomas. The small cell lung cancer cell line NCI-H209, previously shown to
      harbour a point mutation in codon 706: TGT- greater than TTT (Cys- greater than
      Phe), was detected using CDGE. Apart from this control mutant cell line, we did
      not detect any mutations in the examined region in any of the tumors.

PMID- 1381955
TI  - Isochromosome 1q in acute monocytic leukemia: a new nonrandom association.
AB  - We report a case of de novo acute monocytic leukemia in a 25-year-old man in whom
      the sole clonal cytogenetic abnormality was an additional isochromosome 1q.
      Cytogenetic polymorphisms indicate that, in addition to the formation of the
      isochromosome, a duplication of the remaining normal chromosome 1 had taken
      place. Other reported cases suggest an association between acute monocytic
      leukemia and i(1q).

PMID- 1381959
TI  - Determination of the three-dimensional structure of iberiotoxin in solution by 1H
      nuclear magnetic resonance spectroscopy.
AB  - The solution structure of chemically synthesized iberiotoxin, a scorpion toxin
      that blocks Ca(2+)-activated K+ channels, has been determined using 2D 1H NMR
      spectroscopy. Analysis of the NOEs, coupling constants, and HN-DN exchange rates
      indicates the structure consists of an antiparallel beta-sheet from residues 25
      to 36, with a type 1 turn at residues 30-31, and a helix from residues 13 to 21.
      The carboxyl-terminal residues form a short, and distorted, third strand of the
      sheet. The NMR data are consistent with disulfide bonds from residues 7 to 28, 13
      to 33, and 17 to 35. The disulfide bridging presents the same profile as in other
      scorpion toxins, where a Cys-X-Cys sequence in a strand of sheet forms two
      disulfide bonds to a Cys-X-X-X-Cys sequence in a helix. Three-dimensional
      structures were generated using the torsion angle space program PEGASUS. The best
      ten structures had an average rmsd over all pairwise comparisons of 1.49 A. The
      average rmsd to a calculated average structure is 1.0 A. The resulting structures
      appear very similar to those of charybdotoxin, a related scorpion toxin.

PMID- 1381958
TI  - Inhibition of leukocyte extravasation with a monoclonal antibody to CD18 during
      formation of experimental intimal thickening in rabbit carotid arteries.
AB  - In the rabbit model of electrically induced intimal thickening, the adherence
      processes of different leukocyte subsets as well as the functional significance
      of leukocyte invasion in the initial migration of smooth muscle cells (SMCs) into
      the intima were studied by using monoclonal antibody (MAb) 60.3 (directed to the
      leukocyte adherence glycoprotein CD18), a known potent inhibitor of leukocyte
      adhesive functions. In control carotid arteries exposed to two periods of
      electrical stimulation within 36 hours, leukocytes, including all granulocyte
      subsets, monocytes, and lymphocytes, invaded the cell-free subendothelium.
      Concomitantly, SMCs were observed to migrate from the media into the intima. In
      the MAb 60.3-treated rabbits, however, neutrophil emigration into the stimulated
      arteries was abolished, whereas mononuclear leukocyte accumulation in the intima
      was only partially inhibited, indicating a complete CD18-dependent mechanism for
      neutrophil extravasation and additional receptor-ligand systems for the
      emigration of mononuclear leukocytes. SMCs moved into the intima despite complete
      blockage of neutrophils and the reduced accumulation of mononuclear cells within
      the subendothelium after MAb administration. These results preclude neutrophils
      as initiators of SMC migration into the intima. The influence of mononuclear
      cells on the migratory behavior of SMCs in intimal thickening formation, however,
      needs further elucidation.

PMID- 1381960
TI  - Conformational changes of HIV reverse transcriptase subunits on formation of the
      heterodimer: correlation with kcat and Km.
AB  - The reverse transcriptase (RT) from the human immunodeficiency virus (HIV) is
      initially expressed as a 66-kDa protein and is subsequently proteolytically
      processed in vivo to form a 66-kDa/51-kDa heterodimer. Comparison of circular
      dichroism spectra of the 66-kDa, 51-kDa, and heterodimeric forms of RT indicates
      that the conversion is accompanied by dramatic changes in subunit conformation.
      The mean residue ellipticity per subunit at 220 nm decreases from -10.7 x 10(3)
      deg cm2 dmol-1 for the 66-kDa protein to -6 x 10(3) deg cm2 dmol-1 for the
      heterodimer. The same loss of ellipticity is observed whether the heterodimer is
      produced by proteolysis or by mixing a separately-expressed cloned 51-kDa subunit
      with the 66-kDa protein. Comparison with the spectrum of the cloned 51-kDa
      protein suggests that much of the conformational change arises from formation of
      the 51-kDa subunit but substantial changes occur in the remaining 66-kDa subunit
      as well. A kinetic analysis was performed to correlate these conformational
      changes with changes in enzyme function. Application of an integrated Michaelis
      Menten equation to the catalysis of poly(dT) formation using a d(pT)20-poly(rA)
      primer-template shows that the kcat for the heterodimer is approximately half
      that of the 66 kDa enzyme, decreasing from 2.9 to 1.2 nucleotides/s upon
      formation of the heterodimer. However, km values for the primer-template decrease
      from 0.54 to 0.12 microM upon heterodimer formation. Thus, kcat/Km is 2-fold
      larger for the heterodimer, giving it a distinct catalytic advantage at
      undersaturating concentrations of enzyme and primer-template.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1381961
TI  - Lipoxin generation by permeabilized human platelets.
AB  - Human platelets convert leukocyte-derived leukotriene (LT) A4 to lipoxins during
      transcellular lipoxin biosynthesis. Here, we examined lipoxin generation in
      intact human platelets and compared it with that elicited from permeabilized
      platelets. Conversion of LTA4 to lipoxins by permeabilized cells exceeded (10-15
      times) that to peptidoleukotrienes, while intact cells exposed to thrombin
      generated similar amounts of these two series (LT/LX). Permeabilized platelets
      also generated 3-5 times more lipoxins than intact cells. Lipoxin A4 (LXA4),
      lipoxin B4 (LXB4), and their respective all-trans isomers were identified by
      physical methods including HPLC and GC-MS. Chiral analysis of platelet-derived
      all-trans-containing LXs revealed that greater than 69.5 +/- 0.5% carried alcohol
      groups in the R configuration at carbons 6 and 14 (e.g., 11-trans-LXA4 and 8
      trans-LXB4), respectively. More than 50% of these all-trans LX were formed by
      isomerization of native LXA4 and LXB4 during isolation. Lipoxin formation with
      permeabilized platelets gave an apparent Km of 8.9 microM and Vmax of 83.3
      ng/(min-10(9) platelets) with maximal conversion in pH range 7-9. In addition,
      permeabilized platelets converted 14,15-LTA4 and LTA5, but not LTA3, to lipoxins.
      Consecutive exposure to LTA4 did not alter LXA4 generation but inhibited LXB4 by
      40-50%, suggesting that LXB4 formation can be regulated by suicide inactivation.
      Unlike platelets, human endothelial cells did not convert LTA4 to lipoxins. These
      results indicate that lipoxin formation is a major route of LTA4 metabolism in
      thrombin-activated platelets and those that have undergone a loss of membrane
      barriers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381962
TI  - Binding properties and DNA sequence-specific recognition of two bithiazole-linked
      netropsin hybrid molecules.
AB  - We report the DNA binding properties of two hybrid molecules which result from
      the combination of the DNA sequence-specific minor groove ligand netropsin with
      the bithiazole moiety of the antitumor drug bleomycin. The drug-DNA interaction
      has been investigated by means of electric linear dichroism (ELD) spectroscopy
      and DNase I footprinting. In compound 1 the two moieties are linked by a flexible
      aliphatic tether while in compound 2 the two aromatic ring systems are directly
      coupled by a rigid peptide bond. The results are consistent with a model in which
      the netropsin moiety of compound 1 resides in the minor groove of DNA and where
      the appended bithiazole moiety is projected away from the DNA groove. This
      monocationic hybrid compound has a weak affinity for DNA and shows a strict
      preference for A and T stretches. ELD measurements indicate that in the presence
      of DNA compound 2 has an orientation typical of a minor groove binder. Similar
      orientation angles were measured for netropsin and compound 2. This ligand which
      has a biscationic nature tightly binds to DNA (Ka = 6.3 x 10(5) M-1) and is
      mainly an AT-specific groove binder. But, depending on the nature of the sequence
      flanking the AT site first targeted by its netropsin moiety, the bithiazole
      moiety of 2 can accommodate various types of nucleotide motifs with the exception
      of homooligomeric sequences. As evidenced by footprinting data, the bithiazole
      group of bleomycin acts as a DNA recognition element, offering opportunities to
      recognize GC bp-containing DNA sequences with apparently a preference (although
      not absolute) for a pyrimidine-G-pyrimidine motif. Thus, the bithiazole unit of
      bleomycin provides an additional anchor for DNA binding and is also capable of
      specifically recognizing particular DNA sequences when it is appended to a
      strongly sequence selective groove binding entity. Finally, a model which
      schematizes the binding of compound 2 to the sequence 5'-TATGC is proposed. This
      model readily explains the experimentally observed specificity of this netropsin
      bithiazole conjugate.

PMID- 1381963
TI  - Occupancy of the cancer cell urokinase receptor (uPAR): effects of acid elution
      and exogenous uPA on cell surface urokinase (uPA).
AB  - The development of a simple, sensitive fluorimetric assay for the measurement of
      cell surface-associated urokinase plasminogen activator (uPA) on viable, adherent
      HCT116 cells in microtitre plates, after a preincubation with purified human
      plasminogen is described. The assay determines plasmin activity by the cleavage
      of H-D-Val-Leu-Lys 4-aminomethyl coumarin under near physiological pH and ionic
      conditions with a sensitivity in the range of 5-100 mIU uPA/well at excitation
      355 nm and emission 460 nm. Plasmin generated during the assay converted all cell
      surface sc-uPA to tc-uPA, allowing the determination of total uPA activity.
      Inhibitor studies (PAI-2, amiloride or Glu-Gly-Arg chloromethylketone) confirmed
      the specificity of the uPA assay. Removal of these agents prior to assay allowed
      determination of the cell surface sc-uPA:tc-uPA ratio. Cell surface activity was
      only partially removed by acid elution. This corresponded with the loss of a
      number of proteins and uPA-containing species as detected by SDS-PAGE, gelatin
      enzymography and Western blotting. Although the major protein species eluted had
      a M(r) of 55 kDa, reacted with a commercial anti-human uPA mAb and correlated
      with the main lytic zone, other higher M(r) species were also eluted from HCT116
      cells. Exogenous uPA increased cell-surface activity markedly on cells previously
      treated with acid. Following acid elution, cell surface uPA activity was restored
      after 30h in culture suggesting either de novo synthesis or release of pre-formed
      uPA with subsequent secretion and binding to uPAR. The assay has enabled studies
      on adherent cells to address questions about the regulation and expression of
      cell-surface uPA.

PMID- 1381964
TI  - Enhanced intracellular stability of dextran-horse radish peroxidase conjugate: an
      approach to enzyme replacement therapy.
AB  - Horse radish peroxidase (HRP), a mannose-containing glycoprotein was covalently
      modified by conjugation with dextran. The rapid uptake of HRP by the liver is
      markedly inhibited by mannan. The uptake of dextran-HRP conjugate by the liver,
      though lower compared to that of the free enzyme, is also partially inhibited by
      mannan. Liposomes were therefore used as carriers for delivering the free and the
      modified HRP to the liver. The dextran-HRP conjugate showed greater stability
      intracellularly as compared to the free enzyme. The enhanced stability of enzymes
      upon their extensive glycosylation with nondegradable sugar polymers would be of
      importance in extending the catalytic life of therapeutically active enzymes and
      thereby improve their therapeutic potential for the treatment of certain enzyme
      deficiency disorders.

PMID- 1381965
TI  - Enzyme immunoassays for anti-hepatitis C virus antibodies improved specificity
      and analytical sensitivity by combination of three different recombinant viral
      proteins in second generation tests.
AB  - The detection of hepatitis C virus infection currently relies on a "virology
      without a virus" approach. So far, only viral nucleic acid has been isolated and
      sequenced by the methods of genetic engineering. The resulting viral sequence was
      then used to "design" proteins for diagnostic use as antigens in enzyme
      immunoassays (EIA). A first-generation EIA (EIA I), which uses a non-structural
      hepatitis C virus protein as antigen, detected 26 (0.6%) reactive sera out of a
      total of 4350 blood donors. An inhibition test using recombinant hepatitis C
      virus antigen, and EIAs using other, both synthetic and recombinant hepatitis C
      virus peptides were used as a specificity enhancing measure and as confirmatory
      tests, respectively. Only 7 of these reactives (0.16%, inhibition test) and 5
      (0.11%, peptide EIA) were confirmed positive. Of the 26 initially reactive donor
      sera, 5 sera (0.11%) reacted positive in a second-generation anti-hepatitis C
      virus antibody EIA (EIA II), which uses two different recombinant non-structural
      hepatitis C virus proteins and one recombinant core protein. Seventeen (77%) of
      22 haemophiliacs reacted positive in EIA I, and 19 (86%) did so in EIA II. There
      were no false positives in this cohort. Twenty-eight (19%) out of 148 liver
      disease patients showed a positive reaction in EIA I, and 31 (21%) were reactive
      in EIA II. Based on the results of the peptide enzyme immunoassay, 1 serum of
      this group was false positive in EIA I, while none of the sera of this group were
      false positive in EIA II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381966
TI  - Clinical validity of a continuous colorimetric method for serum lipase.
AB  - The clinical validity of a continuous colorimetric method for measuring
      pancreatic lipase was assessed. 1,2-Diacylglycerol containing long-chain fatty
      acid residues was used as substrate, and the method was adapted to a discrete
      analyser. The dynamic range was ascertained up to at least 30-fold the upper
      reference limit. Precision tests on three control sera yielded overall CVs of
      4.6% (mean value 21 U/l), 2.4% (115 U/l), and 1.0% (386 U/l), respectively. Using
      serum samples from normal subjects and patients with pancreatic and non
      pancreatic disorders, the present method was compared with a turbidimetric method
      (r = 0.997; n = 281) and a homogeneous enzyme immunoassay (r = 0.987; n = 93).
      The reference interval established on 121 healthy subjects was 8-57 U/l (central
      95th percentile, median 22 U/l). The sensitivity of this lipase assay in the
      diagnosis of acute pancreatitis (100%, median 5.6-fold the upper reference limit)
      was equal to that of the pancreatic isoamylase assay, and higher than that of the
      total alpha-amylase assay (88.2%); the specificity for acute pancreatitis with
      respect to a group of patients with acute and chronic non-pancreatic abdominal
      diseases (91%) was higher than that of both pancreatic isoamylase (76%) and total
      alpha-amylase (71%).

PMID- 1381967
TI  - Influence of laminin or fibroblasts upon colony formation in the mouse by B16
      melanoma cell spheroids: a morphometric analysis.
AB  - By microscopical observation and using an original morphometric method, we
      analyzed on histological sections the rate of lung colony formation after the
      intravenous injection into the mouse of B16 melanoma cells previously cultivated
      in vitro as aggregates. After the injection of B16 pure spheroids, superficial
      lung colonies were more numerous than internal lung colonies. After the injection
      of mixed spheroids (B16 + 3T3 fibroblasts), the size of colony sections was
      increased. Addition of laminin to pure or mixed spheroids decreased the size of
      colony sections but increased the number of internal lung colonies.

PMID- 1381968
TI  - Effects of some natural products as components of Chinese herbal medicines on
      mammary gland growth and function in mice.
AB  - As a possible step to evaluate the role in the mammary glands of the scales of
      Guanshanjia, the fruits of Lulutong and the seeds of Wangbuliouxing, which are
      the natural products used widely as the components of herbal medicine in China
      for the improvement of lactation and the therapy of breast disorders, the effects
      of these agents on mammary gland growth and function were studied in female mice.
      The chronic administration of each agent in drinking water improved several
      parameters; however, the mode of action differed markedly among agents. The
      results indicate the necessity of acquiring enough knowledge of the
      characteristics of each agent for the efficient prescription of herbal medicine
      as well as the single use of the agent.

PMID- 1381969
TI  - Changes in PSA and early diagnosis of cancer of the prostate.
AB  - During the last four years approximately 400 men were evaluated in the early
      detection program for prostate cancer at The Ohio State University. Of these 400
      men, 25 were found to have cancer. Eleven of the 25 had normal PSAs at the time
      cancer was diagnosed. The rise with a Hybritech assay, PSA of 1.2 ng/ml per year,
      one to two and subsequent years of greater than 1.2 ng/ml in this study indicates
      a higher likelihood of having a diagnosis of prostate cancer. Of the 25 patients
      who have been evaluated, only 4 patients had a subsequent drop of PSA from year
      one to two when the value dropped less than 0.6 ng/ml. Prostate intraepithelial
      neoplasia grade III has also been associated in these patients.

PMID- 1381971
TI  - An infection control bulletin as an educational tool: is it useful?
AB  - For five years a bulletin has been issued to provide information, increase
      awareness and educate staff on current issues and problems in infection control.
      To obtain readers' feedback on the value of receiving this one-page bulletin, an
      evaluation was conducted with the following objectives: to evaluate the content
      and structure in terms of relevant and current information; to evaluate the
      format; and to obtain information on frequency and suggested topics. Categories
      for response were: poor, fair, good and excellent. All respondees (67) rated the
      topics as good to excellent in the current and applicable category. The detail
      and clarity were rated as good/excellent by 59 of 67 (88%) and 59 of 67 (88%) of
      the respondees, respectively. The majority, 61 of 67 (91%), indicated the
      references were useful. The readability, organization and length were rated as
      good/excellent by 63 of 67 (94%), 62 of 67 (92.5%) and 65 of 67 (97%),
      respectively. All but one wished to remain on the mailing list. The results of
      this evaluation and the list of suggested topics for future bulletins support the
      conclusion that the infection control bulletin is a useful educational tool.

PMID- 1381970
TI  - Cross-sectional survey of HIV infection among patients with tuberculosis in
      Nairobi, Kenya.
AB  - Evidence from many countries suggests an association of human immunodeficiency
      virus (HIV) infection and tuberculosis of major public health significance. In
      order to begin assessing the impact of HIV on tuberculosis in Kenya, we have
      determined the HIV-1 seroprevalence among tuberculosis patients and compared the
      clinical characteristics of tuberculosis in HIV-positive and HIV-negative
      patients in two cross-sectional studies at the Infectious Disease Hospital (IDH)
      and the Ngaira Avenue Chest Clinic (NACC), Nairobi, Kenya. The diagnosis in 92%
      of all patients with pulmonary tuberculosis was confirmed by culture. The
      remainder were diagnosed on histological, clinical or radiological grounds. HIV
      seroprevalence among tuberculosis patients at IDH was 26.5% (52/196) compared to
      9.2% (18/195) at NACC (P less than 0.001). There was no association between
      numbers of streptomycin injections in the previous 5 years and HIV infection.
      Positive sputum smear rates in HIV-positive patients were slightly lower than in
      HIV-negative patients at both study sites (71% vs 83% at IDH and 73% vs 82% at
      NACC) but the difference was not significant. Only Mycobacterium tuberculosis was
      isolated. Miliary disease was not associated with HIV infection. Persistent
      diarrhoea, oral candidiasis, generalized itchy rash, herpes zoster and
      generalized lymphadenopathy were all associated with HIV infection, but 46% (95%
      CI:38-54%) of all HIV-positive patients had none of the clinical features listed
      in the WHO Clinical Criteria for the Diagnosis of AIDS, apart from fever, cough
      and weight loss. Stevens-Johnson Syndrome was reported in 7/52 (13%) patients
      with HIV infection, and in 4/144 (3%) patients without (RR 4.85, 95% CI: 1.45
      15.88).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1381972
TI  - Effects of 5-aza-2'-deoxycytidine and interferon-alpha on differentiation and
      oncogene expression in HL-60 myeloid leukemic cells.
AB  - The antineoplastic effects of 5-aza-2'-deoxycytidine (5-AZA-CdR) and interferon
      alpha (IFN-alpha) on human HL-60 myeloid leukemic cells were investigated. 5-AZA
      CdR and IFN-alpha in combination produced a greater inhibition of DNA synthesis
      and cell growth than either agent alone. The co-treatment produced a synergistic
      reduction in the clonogenicity of the HL-60 leukemic cells. In addition, this
      combination also produced a greater reduction in mRNA expression for c-myc than
      each agent alone. This antileukemic action produced by 5-AZA-CdR and IFN-alpha in
      combination correlated with the increase in induction of differentiation of the
      HL-60 leukemic cells. These results suggest that 5-AZA-CdR and IFN-alpha in
      combination produces an enhancement of their antineoplastic action on HL-60 human
      myeloid leukemic cells.

PMID- 1381973
TI  - Effect of 15-deoxyspergualin, a microbial angiogenesis inhibitor, on the
      biological activities of bovine vascular endothelial cells.
AB  - We found recently that 15-deoxyspergualin, an analog of spergualin, which is an
      antibiotic and includes a spermidine moiety in its structure, exhibits anti
      angiogenic activity. We have now carried out in vitro experiments with bovine
      vascular endothelial cells to determine which events occurring during
      angiogenesis are affected by this microbial angiogenesis inhibitor. 15
      Deoxyspergualin did not inhibit the production of urokinase-type plasminogen
      activator (u-PA) or type IV collagenase by vascular endothelial cells. The direct
      inhibition of u-PA activity by 15-deoxyspergualin was not observed either. The
      angiostatic antibiotic neither affected the migration of vascular endothelial
      cells nor inhibited the endothelial cell proliferation in a two-dimensional
      culture system. We also examined the effect of 15-deoxyspergualin on the
      proliferation of endothelial cells in a three-dimensional culture system
      involving collagen gel, in which cell growth resembles more closely the
      endothelial cell proliferation during in vivo angiogenesis than that in a two
      dimensional culture system without collagen gel. The antibiotic inhibited cell
      proliferation in a dose-dependent manner, indicating that the three-dimensional
      culture system is useful for finding a new angiogenesis inhibitor with a
      different mode of action from those of angiogenesis inhibitors found by using a
      two-dimensional assay system; however, no cause-effect relationship has yet been
      established. Taken together, these results suggest the possible involvement of
      the inhibition of vascular endothelial cell growth by 15-deoxyspergualin in its
      angiogenesis-inhibitory effect. 15-Deoxyspergualin appears to be a promising
      candidate as an angiogenesis inhibitor for controlling aberrant angiogenic
      responses occurring in different states, including tumor development.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1381974
TI  - Protein composition of follicular fluid and oocyte cleavage occurrence in in
      vitro fertilization (IVF).
AB  - The present study was carried out from in vitro fertilization (IVF) attempts to
      analyze further the total and specific protein contents of 47 follicular fluids
      yielding one oocyte. The aim was to find correlations between the follicular
      concentrations of such proteins and the occurrence of coupled oocyte cleavage.
      These findings would be used as markers of IVF outcome. Two groups of follicular
      samples were distinguished: one group with cleavage occurrence (25 cases) and
      another group without cleavage or even fertilization (22 cases). In the group
      with cleavage a significantly higher level was observed for six proteins: C3
      complement fraction and ceruleoplasmin (P less than 0.02), alpha-antitrypsin and
      transferrin (P less than 0.01), and alpha 2-macroglobulin and beta 2
      microglobulin (P less than 0.001). The data are discussed with respect to changes
      in follicle permeability with advancing maturity.

PMID- 1381975
TI  - The permeation pathway of neurotransmitter-gated ion channels.

PMID- 1381976
TI  - The single-nucleotide addition cycle in transcription: a biophysical and
      biochemical perspective.
AB  - This review has summarized the known features of the single-nucleotide addition
      reaction cycle in transcription. The reader will have noted that the information
      available is very incomplete, and that, in some cases, related experiments seem
      to lead to contradictory conclusions. We have tried to point out these
      discrepancies as they occur and to indicate areas where more experimentation is
      needed. We look forward to the day when all the microscopic steps of the single
      nucleotide addition cycle can be identified and defined in thermodynamic,
      kinetic, and structural terms. At that point, we can begin to understand the
      principles that relate these parameters to template position and to the pathway
      of formation of a specific complex. It should be possible to provide specific
      molecular interpretations for observed effects on activation barrier heights to
      elongation and termination (154, 155) and to begin to understand the molecular
      bases of the regulation in these phases of transcription. Much work remains
      before this happy situation can be totally realized, but we feel that now the
      problem can at least be approached at this level. We hope that this review helps
      to illuminate the difficulties that remain.

PMID- 1381977
TI  - A cell line that produces the glycoprotein hormone alpha-subunit contains
      specific nuclear factors similar to those present in thyrotropes.
AB  - A unique characteristics of thyrotrope-specific gene expression is the
      coordinated expression and regulation of the alpha- and beta-subunits of TSH. A
      cell line (alpha TSH) derived from the transplantable mouse thyrotropic tumor
      MGH101A, which no longer expresses the TSH beta-subunit gene but continues to
      secrete large amounts of alpha-subunit, was used as a model to study alpha
      subunit gene expression independent from the TSH beta-subunit gene and was
      compared with the expression in TSH-secreting TtT97 tumors. Transient
      transfection studies showed a striking similarity in the activity of 5' deletions
      of the mouse alpha-subunit gene promoter in both alpha TSH and TtT97 cells and
      localized two regions important for expression that spanned 100 base pairs, from 
      480 to -417 and from -417 to -381. These regions were found to have no activity
      in nonthyrotrope pituitary GH4 cells and L-cell fibroblasts. Analysis of the
      alpha-subunit 5' flanking DNA interactions with alpha TSH and TtT97 nuclear
      extracts showed two DNase I protected sequences, from -474 to -452 and from -447
      to -400, both of which colocalized with the functionally important regions. Gel
      retardation analysis demonstrated the specificity of these interactions, and a
      similar migration of the DNA-protein complexes suggested that protein factors
      were similar in the two cell types. We conclude that the nuclear factors
      necessary for alpha-subunit expression in thyrotropes are retained in alpha TSH
      cells. Moreover, since alpha TSH cells do not express the TSH beta-subunit gene,
      the factors that determine the expression of the alpha-subunit may not be
      sufficient for TSH beta-subunit gene expression.

PMID- 1381978
TI  - Matrix mineralization in hypertrophic chondrocyte cultures. Beta glycerophosphate
      increases type X collagen messenger RNA and the specific activity of pp60c-src
      kinase.
AB  - The phenomenon of chondrocyte hypertrophy is accompanied by the expression of
      type X collagen and the appearance of matrix mineralization. These events are
      also associated with changes in the phosphorylation of intracellular proteins. In
      this study the addition of 10 mM beta-glycerophosphate to hypertrophic
      chondrocytes resulted in stimulation of type X collagen synthesis up to 10 days
      in culture and an increase in the expression of type X collagen mRNA. This was
      followed by the onset of mineralization and the appearance of calcium
      hydroxyapatite. In contrast, the addition of beta-glycerophosphate to non
      hypertrophic chondrocytes failed to induce expression of type X collagen or to
      produce changes in calcium and phosphate. The increased formation of type X
      collagen and of mineral in hypertrophic chondrocytes was accompanied by changes
      in the tyrosine kinase pp60c-src. While the level of c-src protein decreased
      approximately 2.5-fold in hypertrophic chondrocytes after 17 days of beta
      glycerophosphate treatment, the specific activity of pp60c-src kinase increased
      approximately 3-fold in the cells that could be induced to mineralize but
      remained unchanged in cells that did not exhibit this property. Regulation of
      kinase activity may be an important event in endochondral ossification.

PMID- 1381979
TI  - Adhesion molecule expression in human hepatic graft-versus-host disease.
AB  - An immunohistological study of the distribution of three cellular adhesion
      molecules, ICAM-1, VCAM-1 and ELAM-1, was undertaken on normal liver and liver
      biopsies taken from allogeneic bone marrow transplant (BMT) recipients. In normal
      controls, ICAM-1 was seen on vascular endothelium and sinusoidal lining cells,
      and VCAM-1 on Kuppfer cells and dendritic macrophages in portal tracts. ELAM-1
      staining was virtually absent. Biopsies from BMT recipients with histological
      evidence of hepatic graft-versus-host disease (GVHD) showed ICAM-1 expression on
      damaged bile duct epithelium in only one of five cases, in contrast to four of
      five showing epithelial HLA-DR expression. Increased numbers of VCAM-1 positive
      portal tract macrophages were seen in GVHD and also in non-GVHD pathology. No
      increase in vascular endothelial expression of VCAM-1 or ELAM-1 was seen. These
      findings contrast with previous studies on other target sites for GVHD, namely
      skin and gastrointestinal tract, where the expression of all three molecules is
      increased on various cells. Although the lack of adhesion molecule expression in
      the liver in GVHD in this study may be related to the timing of biopsies or
      immunosuppressive therapy, it is likely to represent to some extent variation in
      cell and molecular changes occurring in the different tissues affected by GVHD.

PMID- 1381980
TI  - Cartilage oligomeric matrix protein: a novel marker of cartilage turnover
      detectable in synovial fluid and blood.
AB  - Cartilage oligomeric matrix protein (COMP) is a tissue specific non-collagenous
      matrix protein. We have developed an enzyme-linked immunosorbent assay for the
      detection of this protein in synovial fluid and serum. The protein has been
      quantified in these fluids in patients with rheumatoid arthritis (RA), reactive
      arthritis, juvenile chronic arthritis, osteoarthritis and in sera of control
      subjects. The protein was detectable in all fluids and the synovial fluid levels
      were always higher than in serum in paired samples. The highest knee joint
      synovial fluid levels were found in reactive arthritis patients and the lowest in
      RA patients with advanced destruction of the knee joint. However, the relative
      synovial fluid content of COMP was higher in these RA patients than in patients
      with advanced osteoarthritis. In patients with long-standing reactive synovitis
      the concentrations decreased. This decrease, however, was less marked than for
      proteoglycan concentrations. The serum concentrations were low in patients with
      juvenile chronic arthritis and in patients with RA with advanced cartilage
      destruction of the studied knee joint. In the other groups serum levels did not
      differ between groups or from controls.

PMID- 1381981
TI  - Effects of COMT inhibitors on striatal dopamine metabolism: a microdialysis
      study.
AB  - In vivo microdialysis was used to examine the effect of two new catechol-O
      methyltransferase (COMT) inhibitors, Ro 40-7592 and OR-611, on extracellular
      levels of dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA),
      and 5-hydroxyindoleacetic acid (5-HIAA) in rat striatum. The interactions of the
      COMT inhibitors with nomifensine, clorgyline and deprenyl were also studied. Ro
      40-7592 (3-30 mg/kg, i.p.) decreased dose-dependently the efflux of HVA,
      increased that of DOPAC, and tended to increase that of dopamine. Higher doses of
      OR-611 (30-100 mg/kg, i.p.) also decreased the dialysate level of HVA, increased
      that of DOPAC, and tended to increase that of dopamine. Ro 40-7592 was about ten
      fold as potent as OR-611. Neither of the COMT inhibitors changed dialysate levels
      of 5-HIAA. An OR-611 dose of 10 mg/kg i.p. had no significant effect, in contrast
      to Ro 40-7592, on any of the parameters studied; this dose was thus used to
      differentiate between the effects of central and peripheral COMT inhibition. Both
      nomifensine (15 mg/kg, i.p.) and clorgyline (4 mg/kg, i.p.) alone elevated
      extracellular dopamine levels, and lowered those of DOPAC and HVA, though there
      were quantitative and temporal differences between the drugs. L-Deprenyl (1
      mg/kg, i.p.) alone had no significant effect on any of the compounds measured. Ro
      40-7592 (10 mg/kg, i.p.) potentiated the effect of nomifensine on dopamine
      efflux, and it tended to increase clorgyline-induced dopamine efflux.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1381982
TI  - Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal
      cell death.
AB  - The role of inflammatory cytokines in the pathogenesis of neurological diseases
      is not well understood. The neurotoxic effects of cytokines could be mediated by
      immunostimulation of glial cells to produce toxic concentrations of nitric oxide
      (NO) and reactive nitrogen oxides. Cultured microglia and meningeal fibroblasts,
      but not Type 1 astrocytes, were induced by lipopolysaccharides and cytokines to
      synthesize NO and reactive nitrogen oxides from L-arginine. In co-cultures of
      immunostimulated microglia and cerebellar granule neurons, neurotoxicity was
      blocked by an inhibitor of NO synthase, NG-nitroarginine, and by oxyhemoglobin,
      which inactivates NO. Microglial-induced neurotoxicity was also partially
      attenuated by the N-methyl-D-aspartate (NMDA) receptor antagonists, MK-801 and 2
      amino-5-phosphovalerate (APV). Superoxide dismutase, which stabilizes NO through
      inactivation of superoxide anion, augmented microglial-mediated neurotoxicity
      either alone or in combination with MK-801 or APV. Hence, immunostimulated
      microglia mediate neurotoxicity by NO, reactive nitrogen oxides, superoxide anion
      and NMDA-like substances. These findings suggest a novel role for microglial
      produced NO and reactive nitrogen oxides as a neurotoxic agent in
      neurodegenerative disease states.

PMID- 1381983
TI  - Tachykinins preferentially excite certain complex cells in the infragranular
      layers of feline striate cortex.
AB  - Microiontophoretically administered substance P (SP) affected the visually evoked
      responses (VER) and the spontaneous firing of 22 (14%) of the 152 neurons
      recorded from the striate cortex of anaesthetised cats. Enhancing effects were
      seen in 14 neurons and suppressant actions in 8 neurons. Most of the cells
      excited by SP were located in infragranular layers and had complex receptive
      fields; a few belonged to the movement-sensitive class or responded only weakly
      to visual stimulation. Of the neurons recorded in layer V, about 70% were excited
      by SP; the respective proportions were 8% in layer VI, and 2% in layer IV. Cells
      suppressed by SP had either simple or unimodal receptive fields including
      hypercomplex varieties; most of them were located in layer IVc. The effects of
      other tachykinins (neurokinin A, neurokinin B) and of the NK-3 receptor agonist
      Senktide tested in 36 cells were identical to those of SP with respect to types,
      and intracortical locations, of cells affected. During the enhancement induced by
      the tachykinins functional parameters of the neurons such as orientation and
      direction sensitivity were not substantially affected. It seems likely therefore
      that the effect of tachykinins in the primary visual cortex is not a shaping of
      receptive field properties, but rather a modulation of the general excitability
      of neurons projecting to subcortical centers, in particular to the midbrain and
      pons.

PMID- 1381984
TI  - Ultrastructural morphology of projections from the medial geniculate nucleus and
      its adjacent region to the basal ganglia.
AB  - The efferent projections of the medial geniculate nucleus (MG) and its adjacent
      nuclei to the basal ganglia were studied in the rat by the antero- and retrograde
      tracing methods. Injections of wheat germ agglutinin conjugated to horseradish
      peroxidase into the caudal parts of the striatum and globus pallidus produced
      retrograde neuronal labeling in the medial division of the MG (MGm) and its
      adjacent structures including the suprageniculate, posterior intralaminar and
      peripeduncular nuclei, and substantia nigra pars lateralis. Injections of
      [3H]leucine into the MG and its surroundings resulted in anterograde labeling not
      only in the striatum but also in the globus pallidus. The resulting labeling was
      distributed exclusively in the caudal parts of these two nuclei. The electron
      microscopic autoradiography showed preferential radiolabeling of terminals and
      myelinated axons in both the globus pallidus and striatum. Labeled terminals in
      the pallidum mostly made symmetrical synapses on somata and major dendrites,
      while labeled terminals in the striatum established asymmetrical synapses on
      dendritic spines. These morphological differences in the synapses of the efferent
      systems originating from the MGm and its surrounding region suggest
      functional/chemical differentiations at their target sites in the basal ganglia.

PMID- 1381985
TI  - Distribution of substance P-like immunoreactivity in guinea pig central nervous
      system.
AB  - The distribution of substance P-like immunoreactivity (SP-LI) in the guinea pig
      brain has been studied by immunohistochemistry and the results compared with the
      distribution in similar regions in the rat brain. In both species, dense SP-LI
      staining was found in the median eminence, arcuate hypothalamic nucleus,
      substantia nigra, dorsal raphe and dorsal tegmental nuclei, nucleus of the
      solitary tract, substantia gelatinosa of the spinal trigeminal nucleus, and
      spinal cord. Less dense staining was found in the caudate putamen, globus
      pallidus, nucleus accumbens, habenula, hypothalamic areas, and central grey. SP
      LI cell bodies were found in areas previously described for the rat brain
      including several hypothalamic areas, limbic areas, central grey, and dorsal
      raphe and solitary tract nuclei. The major difference between the two species was
      found in the cortex and hippocampus. The guinea pig cortex contained many more SP
      LI cells and fibres, distributed in layers II-VI, than the rat cortex. The guinea
      pig hippocampus contained marked staining, particularly in the pyramidal cell
      layer of CA1-3 fields of Ammon's horn and in the granular layer of the dentate
      gyrus, and SP-LI cells in the hilus of the dentate gyrus, whereas rat hippocampus
      contained few cells and no regions of dense staining. It is concluded that
      because the guinea pig brain has an extensive distribution of SP-LI in the cortex
      and hippocampus it resembles the primate brain more closely than does the rat
      brain.

PMID- 1381986
TI  - Supraoptic nucleus afferents from the accessory olfactory bulb: evidence from
      anterograde and retrograde tract tracing in the rat.
AB  - Our earlier electrophysiological work provided evidence of a direct input to the
      supraoptic nucleus (SON) from the olfactory bulbs; however, these experiments
      could not determine if the input originated in the main and/or accessory portions
      of the olfactory bulb. Here, a connection between the accessory olfactory bulb
      (AOB) and the SON of the rat was examined using a combination of anatomic
      techniques. We employed neurophysin immunocytochemistry to delineate the
      morphological boundaries of the SON and the proximal arborizations of supraoptic
      dendrites. Accessory olfactory bulb efferents to the SON were studied by
      injection of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP)
      into the AOB. The distribution of retrogradely labeled cells within the AOB was
      also determined after injection of either rhodamine-labeled latex microspheres
      (rhodamine beads) or Fluoro-Gold (FG) into the SON. Neurophysin
      immunocytochemistry revealed that SON dendrites extended beyond the generally
      accepted boundaries of the nucleus, coursing ventrolaterally along the surface of
      the periamygdaloid cortex. Anterograde tract tracing with WGA-HRP labeled AOB
      efferents including a dense plexus of terminals and fibers around the ipsilateral
      SON along the path of the ventrally projecting dendrites. Injections of
      retrograde tracers into the SON resulted in rhodamine bead or FG labeling of
      mitral cells throughout the ipsilateral AOB. Taken together, these anatomic
      studies suggest a direct projection from the accessory olfactory bulb to the SON
      of the rat and thus a vomeronasal organ to SON pathway.

PMID- 1381987
TI  - Hypothalamo-spinal pathways and responses to photoperiod in Syrian hamsters.
AB  - Descending projections from the hypothalamic paraventricular nucleus (PVN) to the
      spinal cord mediate the effects of photoperiod on the reproductive system of
      hamsters. To elucidate the course of these PVN efferent fibers, injections of
      horseradish peroxidase conjugated to either cholera toxin or wheat germ
      agglutinin were made into the T1-C7 region of the spinal cord of hamsters. Four
      sets of descending tracts were identified in males and females. Two sets of
      fibers originated from the medial PVN and exited the nucleus dorsally and
      ventrally, respectively. Most of the descending fibers, however, organized
      themselves into two tracts that exited the PVN laterally. In earlier experiments,
      destruction of these lateral pathways prevented photoperiodic responses in
      hamsters of both sexes.

PMID- 1381988
TI  - Mineralization and bone formation on microcarrier beads with isolated rat
      calvaria cell population.
AB  - Using enzymatically isolated rat bone cells in the presence of cytodex
      microcarrier beads, osteoblastic cell differentiation and bone nodule formation
      were studied at the optical and electron microscopic level. Cytochemical method
      showed an intense alkaline phosphatase activity mainly around the microcarriers
      where the cells have formed multilayers on day 4 of cultures. On day 7 of
      experiment cultures, Von Kossa method stained positively only the cytodex
      microcarriers. During the following days, bone nodule formation was closely
      associated with cytodex microcarriers. In contrast, in control cultures with
      negatively charged glass beads, cells failed to pile up around the glass beads,
      and bone nodule formation occurred randomly in the culture dishes with 24 hour
      delay. Light microscopy observations of experiment cultures revealed the
      formation of nodular structures, with active osteoblastic cells forming a
      mineralized matrix in which osteocytes were present. Transmission electron
      microscopy revealed first, a mineralization process of the surface of the cytodex
      microcarriers which appeared like a granular electron-dense, collagen-free layer
      followed by the deposit of a collagenous matrix. These results indicated that
      cytodex microcarriers provided an excellent matrix for bone cell differentiation
      and mineralization.

PMID- 1381989
TI  - Elevated serum alpha-fetoprotein levels in primary gallbladder carcinoma without
      hepatic involvement.
AB  - BACKGROUND: Elevated serum alpha-fetoprotein (AFP) levels, although frequently
      associated with hepatocellular carcinoma, have also been reported in cases of
      primary gallbladder carcinoma. METHODS: The case of a 56-year-old man with a
      markedly elevated serum AFP level and primary gallbladder carcinoma without
      detectable hepatic involvement is reported. RESULTS: The patient had right upper
      quadrant abdominal pain and a palpable right upper quadrant mass. Computerized
      tomography scan of the abdomen showed a large, subhepatic mass consistent with
      the gallbladder, and normal liver parenchyma. Liver enzyme levels were normal.
      Management included cholecystectomy followed by postoperative radiation therapy
      to the gallbladder bed and portal areas and systemic chemotherapy. At the end of
      therapy, the AFP level had returned to normal. CONCLUSIONS: Gallbladder carcinoma
      is rarely diagnosed before surgery, which sometimes inhibits operative planning.
      AFP may be a useful preoperative tumor marker in differentiating the patient with
      primary gallbladder carcinoma from the patient with gallbladder hydrops.

PMID- 1381990
TI  - Tumor-associated antigen 43-9F is of prognostic value in squamous cell carcinoma
      of the lung. A retrospective immunohistochemical study.
AB  - BACKGROUND: Squamous cell lung carcinoma (SLC), the most frequent type of lung
      cancer, generally is treated surgically and its prognosis is poor. The only
      current clinically useful prognostic criterion is lymph node staging (TNM
      classification). Expression of a novel tumor-associated carbohydrate epitope Gal
      beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3 Gal beta 1
      4Glc identified by the 43-9F monoclonal antibody (MoAb) is associated with the
      growth pattern of SLC cell lines in athymic mice and in vitro. This implies that
      the 43-9F epitope may be related to tumor progression in patients with SLC and
      that, as such, it could be of prognostic value. METHODS: Primary tumor specimens
      from 231 patients with lung carcinoma (130 with SLC, 64 with adenocarcinoma, 10
      with small cell carcinoma, 16 with large cell carcinoma, and 11 with
      adenosquamous carcinoma) were examined by immunohistochemical studies on formalin
      fixed, paraffin-embedded tissue samples for immunoreactivity with an MoAb to the
      43-9F antigen. Univariate and step-wise Cox regression analyses were used to
      compare survival time by histopathologic diagnosis, smoker status, TNM
      classification, and type of surgical treatment. RESULTS AND CONCLUSIONS: Patients
      with 43-9F epitope-positive SLC tumors had a significantly (P less than 0.01)
      better prognosis than patients with epitope-negative tumors. In contrast, no
      association was seen between 43-9F epitope expression and survival time for
      patients with lung adenocarcinomas. Further, the prognostic value of 43-9F
      expression in SLC was found to be superior to the N-classification with the added
      advantage that it requires access only to primary tumor tissue and thus is
      available before therapy.

PMID- 1381992
TI  - Neuroblastoma. Correlation of neuropeptide expression in tumor tissue with other
      prognostic factors.
AB  - BACKGROUND: The neuropeptide contents in neuroblastomas were quantified by
      radioimmunoassay (RIA) to assess their possible biologic significance. METHODS:
      Neuroblastoma tumor tissue was obtained from the primary tumor site before
      therapy in 16 patients with newly diagnosed neuroblastoma and in 7 patients with
      central nervous system medulloblastomas or gliomas. RESULTS: The tumor tissue was
      assayed for vasoactive intestinal peptide (VIP), somatostatin (SRIF), substance
      P, and neurotensin by both immunostaining and RIA techniques. Increased VIP
      levels of 1.2 pg/micrograms DNA or more correlated significantly with cellular
      differentiation (P = 0.003) and favorable disease stage (P = 0.002) in
      neuroblastomas. Increased SRIF contents (greater than 1.3 pg/micrograms DNA)
      correlated with differentiation of the tumor (P = 0.002). Increased VIP and SRIF
      content did not correlate with N-myc oncogene expression or ras oncogene protein
      immunostaining. No VIP was detectable in brain tumors, and other neuropeptides
      were variable in content. CONCLUSIONS: RIA of VIP and SRIF levels in primary
      tumor tissue may offer an independent objective assay of biologic behavior in
      neuroblastoma biopsy specimens.

PMID- 1381993
TI  - Acute phase reactants in predicting disease outcome.
AB  - From the studies which are reviewed above, it is generally apparent that in terms
      of the acute phase response, the initial findings in early inflammatory arthritis
      (particularly rheumatoid arthritis, with which the majority of such studies are
      concerned) have little predictive value for either the functional outcome or
      mortality. The wide interindividual variability in these measurements is also
      likely to limit their clinical usefulness as predictors of disease outcome. The
      trend in certain acute phase reactants may be more useful in indicating disease
      activity, although the number of satisfactory studies in this area is very
      limited.

PMID- 1381991
TI  - A phase II trial of biochemical modulation using N-phosphonacetyl-L-aspartate,
      high-dose methotrexate, high-dose 5-fluorouracil, and leucovorin in patients with
      adenocarcinoma of unknown primary site.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) has modest activity as a single agent in a
      number of human adenocarcinomas. The technique of biochemical modulation has been
      used preclinically to increase the activity of 5-FU. METHODS: With doses based on
      a Phase I study, the authors performed a Phase II trial in patients with advanced
      metastatic adenocarcinoma of an unknown primary site using N-phosphonacetyl-l
      aspartate (PALA), methotrexate (MTX), 5-FU, and leucovorin. In some patients, 5
      phosphoriosyl-l-pyrophosphate (PRPP) and uridine triphosphate (UTP) metabolite
      pools were assayed before and after PALA and MTX to assess metabolite pool
      shifts. RESULTS: Twenty-one patients were treated in this Phase II trial.
      Toxicity was tolerable. Biopsy specimens of tumor tissue showed increases in PRPP
      and decreases in UTP levels in two of three and three of four patients,
      respectively. However, only one objective response was seen, which is not
      different from that expected with 5-FU alone. CONCLUSIONS: Expected PRPP and UTP
      metabolite pool shifts were seen when biochemical modulation was performed with
      these drugs according to this schedule. Because toxicity was mild, more intense
      dose schedules of 5-FU are planned for future studies.

PMID- 1381995
TI  - Amino acids and peptides. XXXIII. Synthesis of N-terminal epitope peptides of
      mammalian metallothioneins (MTs).
AB  - In order to determine the fine structure of the mammalian metallothionein (MT)
      epitope to a monoclonal anti-rat Zn-MT-II antibody (MT 189-14-7), N-terminal
      peptides of various lengths of mammalian metallothioneins (MTs) were synthesized
      by a conventional solution method using the newly developed beta-2
      adamantylaspartate, and their immunological properties were examined. It was
      found that the N-terminal acetyl group was indispensable for the reaction with
      the monoclonal antibody and the N-terminally acetylated pentapeptide, Ac-Met-Asp
      Pro-Asn-Cys-OH, was the smallest peptide which exhibited a significant reactivity
      with the antibody.

PMID- 1381994
TI  - Transcription in maize mitochondria: effects of tissue and mitochondrial
      genotype.
AB  - Mitochondrial run-on assays were used to determine transcriptional rates for nine
      B37(N) maize mitochondrial genes. Quantitation by radiographic imaging detected a
      15-fold range in transcriptional rates; the order of apparent promoter strength
      was rps12 greater than rrn26 greater than atp6 greater than rrn18 greater than
      cox2 greater than atp alpha greater than atp9 greater than cox3 greater than cob.
      By probing single-stranded DNAs of both polarities with the run-on-products we
      showed that gene-specific antisense transcription did not occur. We also tested
      whether relative transcriptional rates were dependent on either the mitochondrial
      genotype or the tissue from which the mitochondria were isolated. Although tissue
      specific differences in transcriptional rates were not detected, significant
      variation in apparent promoter strength for at least one gene, rps12, was
      dependent on the cytoplasmic genotype; rps12 had a five-fold reduced
      transcriptional rate in B37(T), the Texas male cytoplasmic strain of maize. Pulse
      chase experiments suggested that differential transcript stability was not a
      major determinant of steady state mitochondrial RNA levels. These results
      indicate not only that promoter strength is an important component of the
      regulation of transcript levels in maize mitochondria, but also that the strength
      of a specific gene promoter can be dependent on the cytoplasmic genotype.
      Finally, the high transcriptional rate of both ribosomal RNA genes and the one
      mitochondrially encoded ribosomal protein gene studied suggests coordinate
      transcriptional regulation of both RNA and protein components of the
      mitochondrial ribosome.

PMID- 1381996
TI  - Synthesis and anti-human immunodeficiency virus type 1 (HIV-1) activity of 3
      substituted derivatives of 3'-azido-3'-deoxythymidine (AZT), and inhibition of
      HIV-1 reverse transcriptase by their 5'-triphosphates.
AB  - Various 3-substituted 3'-azido-3'-deoxythymidine analogs (2a-i) were prepared by
      the reaction of 3'-azido-3'-deoxythymidine (1), AZT with N,N-dimethylformamide
      dialkylacetal or alkyl bromide in the presence of base and their activities
      against human-immunodeficiency virus type-1 (HIV-1) were evaluated. The
      corresponding 5'-triphosphate analogs (9) were also synthesized in order to
      examine inhibition of HIV-1 reverse transcriptase activity. Beyond expectation,
      some N3-derivatives of AZT were found to reserve the anti-HIV-1 activity to some
      extent. Among the compounds (2a-i) obtained, 3-allyl-AZT (2e) was the most active
      against HIV-1 replication in MT-4 cells in vitro with an EC50 value of 0.9
      microM. 3-Allyl-AZT 5'-triphosphate (9e), however, exhibited no inhibition of HIV
      1 reverse transcriptase activity.

PMID- 1381997
TI  - Antiandrogen. I. 2-azapregnane and 2-oxapregnane steroids.
AB  - 2-Azachlormadinone acetate (5a, 17-acetoxy-6-chloro-2-azapregna-4,6-diene- 3,20
      dione), 2-oxachlormadinone acetate (6, 17-acetoxy-6-chloro-2-oxapregna-4,6-diene
      3,20-dione) and the derivatives were prepared as potential antiandrogenic agents.
      Biological evaluation showed that 5a and 6 had a potent antiandrogenic activity
      when tested in the castrated male rat.

PMID- 1381998
TI  - Flow cytometric measurement of intracellular bilirubin in human peripheral blood
      mononuclear cells exposed to unconjugated bilirubin.
AB  - Human peripheral blood mononuclear cells were incubated at 37 degrees C with
      bilirubin in bovine albumin solution. Histological analysis of bilirubin-treated
      cells demonstrated a prominent brown pigment deposited in the cytoplasm.
      Homogenates of these cells in chloroform-methanol solution showed an identical
      absorption spectrum with pure bilirubin dissolved in the same solution. When
      bilirubin-treated cells were excited at 488 nm, a significant autofluorescence
      was detected by flow cytometry at 585 nm in a dose-dependent manner, which had a
      significant correlation with the amount of bilirubin chemically extracted from
      the cells (r = 0.963, n = 34, p less than 0.001). Intraassay and interassay
      variability of the autofluorescence by flow cytometric analysis was small (both
      less than 5%). When bilirubin-treated cells were stained with fluorescein-labeled
      anti-CD14 antibody, the CD14 positive cell population can be fractionated without
      interference of autofluorescence derived from intracellular bilirubin. These
      results suggest that flow cytometric analysis of bilirubin-treated cells can
      quantitate intracellular bilirubin, and that bilirubin does not interfere with
      analysis of surface antigens.

PMID- 1381999
TI  - Macroamylases: differences in activity against various-sized substrates.
AB  - Hyperamylasemia caused by macroamylases can lead to the overdiagnosis of acute
      pancreatitis. We examined whether interference from macroamylase is less in
      assays that use high-molecular-mass (high-M(r)) substrates rather than
      oligosaccharide substrates. We hypothesized that high-M(r) substrates would be
      sterically excluded from macroamylasemic complexes and thus would be hydrolyzed
      less efficiently. Eighteen macroamylasemic samples were assayed by using red-dyed
      amylopectin or blue-dyed starch as polysaccharide substrates or by using
      maltoheptaose or maltotetraose as oligosaccharide substrates. The oligosaccharide
      substrates gave comparable results (y = 0.81x + 83), but we observed consistently
      lower activities for amylopectin than for maltotetraose (y = 0.32x + 38). We
      observed no bias among methods when nonmacroamylasemic specimens were analyzed.
      The mechanism of this difference was examined by adding antihuman pancreatic
      amylase antibodies to hyperamylasemic serum samples from patients without
      macroamylasemia and to purified human pancreatic or salivary isoamylases. In each
      case, polyclonal and monoclonal antibodies lowered amylase activity more in
      assays with complex polysaccharides than in those with oligosaccharides. The use
      of high-M(r) substrates diminishes interference, and detection of suspected
      macroamylasemia may be possible through comparing activities determined from
      automated methods that use different substrates.

PMID- 1382000
TI  - Influence of a serotonin- and dopamine-rich diet on platelet serotonin content
      and urinary excretion of biogenic amines and their metabolites.
AB  - Using high-performance liquid chromatography and gas chromatography, we
      reevaluated the 24-h influence of a serotonin- and dopamine-rich diet on platelet
      serotonin and serotonin, 5-hydroxyindoleacetic acid (5-HIAA), and major
      catecholamine metabolites in the urine of 15 healthy adults. Although there were
      significant responses in urinary free serotonin and catecholamine metabolites,
      their concentrations did not exceed the upper limits of the reference ranges for
      any of the participants. For urinary 5-HIAA, pronounced effects were observed
      within 2-4 h. After 6-8 h, results for 11 participants exceeded the upper limit
      of the reference range. The median recovery of dietary serotonin as urinary 5
      HIAA was 20% and subject to a large range (1-50%). There was no significant
      change in platelet serotonin. We conclude that, using specific analytical
      methods, no dietary restrictions need be imposed to diagnose catecholamine
      (metabolite)-producing tumors. For diagnosis of carcinoids on the basis of
      urinary 5-HIAA it is appropriate to completely abstain from serotonin-containing
      foods for greater than or equal to 12 h before testing. Platelet serotonin is a
      more sensitive marker for carcinoids that produce only small amounts of
      serotonin, and is unaffected by dietary serotonin.

PMID- 1382001
TI  - Detection of antithyroglobulin autoantibodies with defined epitopic specificity
      by a microparticle-enhanced nephelometric immunoassay.
AB  - To hydrophilic, polyfunctional spherical microparticles of predetermined
      diameter, produced by copolymerization of acrylic monomers, we covalently bound
      human thyroglobulin. The thyroglobulin-microsphere conjugate was agglutinated, in
      the presence of antimouse immunoglobulins antiserum, by four monoclonal
      antibodies, each recognizing a different antigenic domain on the thyroglobulin
      molecule. These agglutinations were quantified by measuring with a specially
      designed nephelometer the light scattered by clusters of the conjugates.
      Agglutination with the monoclonal antibody recognizing antigenic domain II of the
      thyroglobulin molecule was specifically inhibited by some human sera that
      contained antithyroglobulin autoantibodies. This allowed us to develop a
      microparticle-enhanced nephelometric immunoassay for these autoantibodies with
      defined epitopic specificity. Using this assay, we detected and quantified
      antithyroglobulin autoantibodies in serum samples from all eight patients
      examined with Hashimoto disease and from most (75%) patients with untreated
      Graves disease.

PMID- 1382002
TI  - Rhabdomyosarcoma of the head and neck in children.
AB  - Twenty-two children, 9 male and 13 female, with a non-orbital rhabdomyosarcoma of
      the head and neck, treated between 1970 and 1988, have been reviewed. Since 1972,
      treatment has consisted of combination chemotherapy, and where necessary
      radiotherapy and/or surgery. Complete clinical remission after initial
      chemotherapy was observed in 21 children. Six children were cured after primary
      treatment but 15 developed recurrent disease. Thirteen children had a
      parameningeal localized tumour, with eventual meningeal involvement in 5.
      Survival in this group was worse than in the non-meningeal group. Lymph node
      metastasis at first presentation (5 patients) had no influence on prognosis,
      whereas development of lymph node metastases during follow-up resulted in 100%
      mortality. All patients were retrospectively classified according to both the IRS
      classification and TNM-descriptive system. No correlation with either system
      could be established. Fourteen of 15 children with recurrent disease were
      treated, 4 of whom were cured. Thus, 10 out of 22 (45%) children were long-term
      survivors.

PMID- 1382003
TI  - The effects of diuretics on nasal transmucosal potential difference.
AB  - The effects of application of frusemide, amiloride and bumetanide on nasal
      transmucosal potential difference (NTPD), at rest and during exercise, were
      studied in 8 normal subjects. In a double-blind placebo controlled study, 8
      volunteers had NTPD recorded at 4-min intervals during 12-min periods of rest,
      before and after treatment, during 12 min of exercise, and recovery. Application
      of placebo, frusemide and bumetanide did not significantly alter NTPD at rest.
      Amiloride caused a significant reduction (P less than 0.025). During exercise
      there was a significant rise in NTPD with placebo (P less than 0.05), frusemide
      (P less than 0.05) and amiloride (P less than 0.05). There was no increase in
      NTPD during exercise with bumetanide.

PMID- 1382004
TI  - Neurodevelopmental outcome in infants with bronchopulmonary dysplasia.
AB  - It appears that the survivor of BPD is at risk for neurodevelopmental compromise
      but not necessarily to any greater extent than are prematurely born infants in
      general. What appears to be true is that as the neonatal course becomes more
      complicated, and the birth weight drops, the risk increases. If a BPD survivor
      sustains a moderate to severe IVH, particularly if accompanied by periventricular
      leukomalacia, the risk of significant handicap increases substantially. Effects
      of socioeconomic status (SES) are also important, and become more evident over
      time with a direct correlation between SES and outcome. Maximizing the
      environmental conditions while in the special care nursery, and reducing stress
      on the infant during the illness, may help to reduce risk of a compromised
      developmental outcome in the survivors. Careful monitoring of oxygen saturation
      postdischarge may similarly have a positive effect on outcome. Although direct
      comparability among studies is not possible, it appears that most reports suggest
      about half the survivors are free of any handicapping condition at follow-up, and
      about half are either moderately or severely impaired. Cerebral palsy is the most
      frequently reported handicapping condition. Since the presence or absence of
      significant IVH is not consistently reported across studies, it is not possible
      to know if infants who subsequently develop CP sustained a bleed, in addition to
      BPD, in the neonatal period. In studies in which this is more carefully
      delineated, that appears to be the case. In studies in which infants with
      significant hemorrhage were either excluded or dropped out, no survivors with
      cerebral palsy are reported. Approximately 4% of survivors across all studies
      reviewed were blind as a result of severe retinopathy of prematurity. Several
      studies excluded infants who developed significant ROP from their follow-up, so
      this percentage may be an underestimate of the actual incidence across all BPD
      survivors. With a greater number of gestationally younger infants surviving, this
      is one area of handicap that may increase in the years to come. Not all studies
      report on the presence of sensorineural hearing loss in survivors, but there is
      the suggestion this may occur perhaps in up to 4% of survivors. This is an area
      that future research should address. For infants who fall in the moderately
      handicapped category, typically defined as more than one standard deviation below
      the mean on a standardized developmental examination, that rating may change over
      time in either direction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1382005
TI  - Effect of various polyamino acids and D- and L-amino acids on the blood
      fibrinolytic system.
AB  - 1. Comparative additional effects of 24 commercially obtained amino acids and
      their derivatives were studied by the whole blood clot lysis time (WBCLT) method.
      D-Arg and L-Lys (greater than 50 micrograms/ml) activated the fibrinolytic
      system, and poly-L-Glu (mol. wt 6000-90,000) (less than 50 micrograms/ml) were
      less effective. 2. Poly-L-Arg, poly-L-Lys and poly-(Lys-Ala-Glu-Tyr) accelerated
      the TPA inhibition in the presence of human plasma. 3. For in vivo experiments, 5
      mg of poly-L-Glu were given intravenously to 10 rats. 4. The shortening of WBCLT
      and elevation of EFA (P less than 0.01) were found after 1 hr administration. 5.
      The main enzymes which increased in plasma were proved to be the endogenous
      plasminogen activators with mol. wt higher than 70,000, by zymography.

PMID- 1382006
TI  - Platelet immunology. ELISA for detection of platelet antibodies, platelet
      specific antigens and platelet glycoproteins.
AB  - The development of an enzyme linked immuno-sorbent assay (ELISA) for detection of
      platelet antibodies and platelet specific-antigens has been described. In the
      assay, intact platelets fixed to the bottom of microplates have been used as
      targets. After incubation with serum, the attached antibody has been detected by
      antiglobulin serum labelled with enzyme followed by assay of the enzyme reaction
      with its substrate. The clinical significance of platelet antibodies in
      alloimmune neonatal thrombocytopenia (AINT), post-transfusion purpura (PTP), and
      refractoriness to platelet transfusion therapy has been described. The clinical
      significance of autoantibodies in autoimmune thrombocytopenic purpura (AITP) and
      the detection of platelet surface glycoproteins by a modification of the platelet
      ELISA has also been described. In addition, a survey of the present state of
      knowledge of human platelet immunology, especially platelet-specific alloantigens
      and alloantibodies has been given. The studies of AINT and PTP have revealed a
      human immune response gene located in the MHC region: The susceptibility to anti
      Zwa alloimmunization is strongly associated with the HLA-B8 and even more DR3 and
      DRw52a tissue types. In the studies of PTP, the first example of PTP due to anti
      Zwb (only detectable in the platelet ELISA) has been described, and an
      association of the presence of anti-Zw antibodies of IgG3 subclasses (defined in
      the platelet ELISA using monoclonal mouse antibodies) and destruction of
      autologous platelets has been described. In an investigation of Ig classes and
      IgG subclasses of platelet associated Ig (PAIg) in children suffering from
      autoimmune thrombocytopenic purpura, no correlation was found between the
      immunochemical properties of the PAIg and the clinical course of the disease.
      However, a correlation between increased amounts of PAIgG3 and very low platelet
      counts was observed. A modification of the platelet ELISA using monoclonal
      antibodies against glycoproteins (GP) has been described. Using antibodies
      against GPIb and GPIIb/IIIa, it has been possible to diagnose Glanzmann's
      thrombasthenia (GT) and Bernard-Soulier syndrome (BSS). Especially in the
      diagnosis of thrombocytopenic patients suspected for BSS where platelet
      aggregation studies has been impossible due to low platelet counts, the detection
      of decreased amounts of surface GPIb in ELISA has been of great value. In
      conclusion, the platelet ELISA has been found simple and sensitive, and suitable
      for routine investigations of AINT, PTP, AITP, and refractoriness to platelet
      transfusion.

PMID- 1382007
TI  - Psychosis and idiopathic precocious puberty in two 7-year-old boys.
AB  - The authors present case reports of psychosis and idiopathic precocious puberty
      (IPP) with tall stature in two 7-year-old boys. Other similarities in the two
      cases are discussed. Review of the literature revealed only one report regarding
      the role of accelerated sexual maturation in the clinical picture of psychoses in
      children and one case report of Pervasive Developmental Disorder and IPP in a 5
      year-old girl. Possible mechanisms by which psychosis and IPP with tall stature
      may be related are discussed.

PMID- 1382008
TI  - Chromosome detection by in situ hybridization in cancer cell populations which
      were flow cytometrically sorted after immunolabeling.
AB  - We examined the feasibility of performing non-radioactive in situ hybridization
      (ISH) in flow cytometrically sorted (tumor) cells with a chromosome #1 specific
      centromere probe. The study was performed in a model system of HL60 cells mixed
      with different quantities of HeLa cells. These latter cells were sorted directly
      onto poly-l-lysine coated glass slides on the basis of their keratin content, a
      cytoskeletal component not present in HL60 cells. Overall morphology of the
      separated HeLa cells was excellent and, after the ISH procedure, the appropriate
      number of ISH spots was observed in more than 85% of the sorted cells. This
      percentage did not differ significantly in cell mixtures with different
      percentages of HeLa cells (down to 1%). Sorting of HeLa cells in different phases
      of the cell cycle, and subsequent ISH, revealed the same spot number for
      chromosome #1 in all cell cycle stages, including mitosis. In the latter phase of
      the cell cycle we did not find a duplication of the chromosome #1 centromere, not
      even after sorting of the mitotic cells on the basis of specific labeling with an
      antibody to mitotin. The early G2 mitotin negative fraction, however, showed a
      significant percentage of cells with a duplicate spot number, most likely
      representing a tetraploid cell fraction in this HeLa cell culture. The protocol
      that evolved from these model studies was applied to cell suspensions of
      malignant body cavity effusions as well as solid bladder carcinomas. In several
      of these cases numerical chromosome aberrations could be detected by ISH more
      evidently after sorting on the basis of keratin labeling.

PMID- 1382009
TI  - Analytical methods for the study of liver cell proliferation.
AB  - Various cytometric methods for analysis of regenerating rat liver growth (DNA
      ploidy distributions, binucleation, and DNA synthesis by in vivo BrdUrd
      incorporation) were evaluated. The overall hepatocellular growth rate (labeling
      index), the binucleation rate, and separate indices for mononuclear and binuclear
      cells could be measured simply by microscope counting of collagenase-isolated
      hepatocytes immunostained for BrdUrd. Flow cytometry of cells stained for BrdUrd
      and DNA provided labeling indices for the various hepatocellular DNA ploidy
      classes as well as for nonparenchymal cells (identified by their size-dependent
      light scatter), but could not distinguish between mononuclear and binuclear
      hepatocytes. Image cytometry, using fluorescence or Feulgen staining, was
      inferior to flow cytometry in terms of speed and DNA resolution, but allowed a
      complete analysis of all hepatocellular DNA ploidy and nuclearity classes. It may
      therefore be the method of choice, particularly for analysis of liver cell
      cultures from which single cells are not easily obtained. Fluorescence staining
      would seem to be preferable to Feulgen staining, since the latter could not be
      used simultaneously with BrdUrd staining and therefore required a two-step
      analysis. A non-immunological method, based on the ability of incorporated BrdUrd
      to quench DNA staining by a Hoechst dye, could only be applied to isolated
      nuclei, thus giving no information about binucleation. The latter method may be
      useful for analysis of tumors which are difficult to dissociate to intact whole
      cells.

PMID- 1382010
TI  - Sequential paraformaldehyde and methanol fixation for simultaneous flow
      cytometric analysis of DNA, cell surface proteins, and intracellular proteins.
AB  - A cell fixation and permeabilization procedure consisting of sequential
      paraformaldehyde and methanol was evaluated and found suitable for concomitant
      flow cytometric quantification of total cellular DNA, immunofluorescence
      measurements of cell surface proteins, and immunofluorescence measurements of
      intracellular proteins. Paraformaldehyde/methanol-fixed cells exhibited
      significantly greater intracellular antitubulin immunofluorescence than cells
      fixed with paraformaldehyde or methanol alone (p less than 0.002) and
      significantly greater intracellular antitubulin immunofluorescence than cells
      fixed with methanol followed by paraformaldehyde (p less than 0.006). With
      paraformaldehyde/methanol fixation, cell morphology was well preserved and
      forward and right angle light scatter properties were sufficiently well
      maintained to permit gating on these parameters. Cell surface marker staining
      with fluorescent anti-leukocyte antibodies was unaffected by fixation with
      paraformaldehyde/methanol. Paraformaldehyde effects on the intensity of DNA
      staining with propidium iodide were dependent on paraformaldehyde concentration
      and fixation temperature; these effects were least pronounced at low
      paraformaldehyde concentrations (0.25% or less), and at temperatures lower than
      37 degrees C. Paraformaldehyde fixation may result in differences in propidium
      iodide staining of DNA in some diploid cells, which may produce small spurious
      aneuploid peaks in normal peripheral blood leukocytes. Paraformaldehyde fixation
      also produces an apparent increase in the DNA index of aneuploid cell populations
      in comparison with methanol fixation, particularly when the DNA index exceeds
      1.5. Occasionally, this paraformaldehyde fixation-induced effect is useful in
      identifying biologically distinct near-diploid subpopulations in tumors.

PMID- 1382011
TI  - Benzodiazepines. Depressants or antidepressants?

PMID- 1382012
TI  - Multiple myeloma. New treatment options.
AB  - Before proceeding to treatment selection for multiple myeloma, it is important to
      exclude monoclonal gammopathy of unknown significance or any similar smouldering
      or indolent type of myeloma not requiring immediate chemotherapy. In patients
      with active myeloma, pretreatment prognostic classification is important for
      appropriate balancing of the risks and benefits of particular treatment options.
      For example, conventional chemotherapy such as melphalan/prednisone may be
      appropriate for an elderly patient with active stage III myeloma, whereas high
      dose chemotherapy with or without bone marrow transplantation or cytokine support
      may be considered for the patient under age 45 with even earlier stage disease. A
      variety of options are now available for patients with relapsing or resistant
      disease, particularly using agents with potential for reversal of multi-drug
      resistance. The use of interferon-alpha as maintenance following initial response
      to chemotherapy is important for prolongation of remission, duration and
      potentially survival. A variety of supportive measures are also helpful including
      the use of epoetin (erythropoietin) to improve refractory anaemia and
      bisphosphonates for the inhibition of ongoing bone resorption. With the
      availability of various treatment options, it has become important for patients
      to be evaluated by a specialist in the field.

PMID- 1382013
TI  - Newer neuromuscular blocking drugs. An overview of their clinical pharmacology
      and therapeutic use.
AB  - Four new nondepolarising muscle relaxants, pipecuronium bromide, doxacurium
      chloride, mivacurium chloride and Org 9426 (rocuronium) offer alternatives to the
      established agents atracurium besilate and vecuronium bromide. Pipecuronium and
      Org 9426 are steroidal compounds, the latter being a monoquaternary agent,
      whereas doxacurium and mivacurium are bisquaternary benzylisoquinolinium
      compounds. Pipecuronium and doxacurium have a relatively slow onset and a long
      duration of action. Pipecuronium produces maximum block in 3 to 6 min when given
      in a dose of 45 to 80 micrograms/kg, and a duration of clinical relaxation of
      between 40 and 110 min. Doxacurium is more potent, but is the least rapid and the
      longest acting relaxant currently available. When administered in doses of 37 to
      80 micrograms/kg, it produces maximum block within 3.5 to 10 min, with a duration
      of clinical relaxation of 77 to 164 min. The advantage of both pipecuronium and
      doxacurium is their cardiovascular stability. Both agents are primarily
      eliminated via the kidneys and both have now been licensed for use in the US.
      Mivacurium is a muscle relaxant with a short duration of action. When
      administered in doses of 0.1 to 0.25 mg/kg it produces maximum block in 2 to 4
      min, but the duration of clinical relaxation is less than 20 min. Higher doses
      which could induce a faster neuromuscular block are unfortunately associated with
      some histamine liberation. The drug is metabolised by plasma cholinesterase.
      Mivacurium has also been licensed for use in the US. Org 9426 is an agent with a
      rapid onset but an intermediate duration of action. A dose of 0.5 to 0.6 mg/kg
      induces maximum block in about 1.5 min and has a duration of clinical relaxation
      of about 30 min. The rapid onset of effect could be useful for early intubation
      as an alternative to suxamethonium chloride. However, much more clinical
      experience is needed with this agent, particularly with regard to duration of
      action of larger doses and occurrence of side effects. The drug is mainly
      eliminated via the liver.

PMID- 1382014
TI  - Drug treatment of the irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is defined as a functional bowel disorder in which
      abdominal pain is associated with defecation or a change in bowel habit, and with
      features of disordered defecation and distension. The irritable bowel syndrome
      occurs in 10 to 20% of people worldwide and is very commonly encountered in
      clinical practice. This has encouraged the pharmaceutical industry to search for
      effective drug therapy. So far, a universally effective agent has not been found,
      and since this is a chronic, benign disorder, beginning in youth, long term drug
      use should be avoided. Nevertheless, if a specific IBS symptom, such as
      constipation or abdominal pain dominates, a specific drug may be helpful.
      However, tests and treatment should be minimised or even avoided in order to do
      no harm. A largely nonpharmaceutical approach to IBS should be taken. This
      approach employs drugs sparingly and then only targeted at specific and resistant
      symptoms.

PMID- 1382015
TI  - Effective treatment of urethritis. A practical guide.
AB  - Most cases of urethritis can be readily treated using recommended regimens. The
      most important causes of urethritis are Chlamydia trachomatis and Neisseria
      gonorrhoeae, and initial treatment is directed at them. Optimal management
      requires obtaining a thorough sexual history, evaluation for objective clinical
      and laboratory evidence of infection, antimicrobial therapy directed towards the
      major aetiologies, and evaluation and treatment of sexual partners. Treatment of
      gonorrhoea requires a single-dose regimen active against N. gonorrhoeae, plus a
      regimen active against C. trachomatis and nongonococcal urethritis. The usually
      recommended treatment for N. gonorrhoeae is a single dose of ceftriaxone 250mg
      intramuscularly, but there are many alternatives, including oral ones. Only in
      very restricted geographical areas and under restricted situations are
      penicillins still reliable against N. gonorrhoeae. Recommended optimal treatment
      of C. trachomatis or nongonococcal urethritis currently requires 7 days'
      treatment with a tetracycline. Some guidelines now propose ofloxacin 300 mg
      orally twice daily for 7 days as an equivalent alternative, and there are very
      promising data with a single dose therapy with azithromycin, a long-acting
      macrolide antimicrobial. Using recommended regimens, microbiological failure is
      infrequent in compliant patients. Recurrent urethritis is, however, frequent. For
      patients who receive recommended treatment and do well, no follow-up cultures are
      needed. Patients with persistent or recurrent symptoms require careful re
      evaluation of the patient, documentation of urethritis, and retreatment with
      antimicrobial agents a second time if urethritis is documented by positive
      cultures or increased numbers of polymorphonuclear leucocytes in urethral
      secretions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382016
TI  - Diabetes insipidus. Current treatment recommendations.
AB  - Cranial diabetes insipidus (DI) arises when release of arginine vasopressin (AVP,
      antidiuretic hormone) in response to osmotic stimuli is inadequate. The correct
      diagnosis and management of cranial DI is particularly important when it arises
      as an acute complication of surgery, trauma or in subjects who lack thirst
      sensation. Desmopressin (1-desamino-8-D-arginine-vasopressin, DDAVP) provides an
      effective and convenient replacement therapy when given by the intranasal route.
      However, nasal administration is difficult for some patients, and in the future
      oral or transcutaneous desmopressin formulations may prove to be satisfactory
      alternatives. By contrast, treatments for nephrogenic DI, where there is failure
      of the antidiuretic response to endogenous or exogenous vasopressin, have been
      disappointing and water replacement remains the mainstay of therapy. An
      understanding of the physiology and pathophysiology of water homeostasis and
      correct interpretation of water balance and electrolyte data are essential for
      correct diagnosis and management of all cases of DI.

PMID- 1382017
TI  - Lansoprazole. A review of its pharmacodynamic and pharmacokinetic properties and
      its therapeutic efficacy in acid-related disorders.
AB  - Lansoprazole is an effective acid pump inhibitor acting at the final enzymatic
      step of the acid secretory pathway of the parietal cell, decreasing gastric acid
      secretion regardless of the primary stimulus. Results of short term (less than 8
      weeks) clinical trials have shown lansoprazole to be significantly superior to
      placebo and ranitidine in the treatment of duodenal ulcer, both in the rate of
      healing and in overall healing at 4 weeks. Lansoprazole appears to heal duodenal
      ulcer more quickly than famotidine, and demonstrates slightly greater efficacy at
      4 weeks, although both drugs appear to have equivalent efficacy overall. Gastric
      ulcers and reflux oesophagitis are also healed by lansoprazole 30 mg/day for 4 to
      8 weeks, with healing rates after 8 weeks of approximately 85 to 95% for both
      indications. Lansoprazole appears to be superior to ranitidine and comparable to
      omeprazole in treating reflux oesophagitis. Furthermore, lansoprazole has
      relieved reflux symptoms more quickly than either ranitidine or omeprazole.
      Preliminary data also indicate that lansoprazole may be effective in the
      treatment of peptic ulcer disease and reflux oesophagitis refractory to H2
      receptor antagonists, and in patients with Zollinger-Ellison syndrome. While
      direct comparisons with omeprazole are limited, results suggest that
      lansoprazole, used for short term treatment, is at least as effective as
      omeprazole in the treatment of peptic ulcer and reflux oesphagitis. Lansoprazole
      has been well tolerated in short term clinical trials, with an incidence of
      adverse effects comparable with that of other agents in its therapeutic class.
      Trials assessing long term tolerability data are ongoing and will be required as
      part of the assessment of the safety profile, if lansoprazole is to be used
      prophylactically to prevent ulcer recurrence. Thus, by virtue of its ability to
      heal ulcers and rapidly relieve associated symptomatology, lansoprazole
      represents a useful alternative for the treatment of acid related disorders.

PMID- 1382019
TI  - Effects of substance P on extracellular dopamine in neostriatum and nucleus
      accumbens.
AB  - Microdialysis was used to monitor changes in dopamine release in the neostriatum
      and nucleus accumbens after peripheral administration of substance P in freely
      moving rats. Substance P in a dose of 50 micrograms/kg produced a steady moderate
      increase in dopamine levels in the neostriatum, which persisted for at least 5 h.
      In contrast, a dose of 250 micrograms/kg caused an acute increase in dopamine
      levels in the nucleus accumbens, which lasted about 2 h. These data suggest that
      the peripheral administration of substance P can influence dopamine release in
      mesolimbic and mesostriatal terminals.

PMID- 1382020
TI  - Characterization of cell selectivity of two novel inhibitors of nitric oxide
      synthesis.
AB  - We have assessed the capacity of two novel inhibitors to block cytokine-induced
      nitric oxide (NO) synthesis by macrophages and vascular smooth muscle cells, as
      well as NO production by the constitutive enzyme in central nervous system
      tissue. NG-Cyclopropyl-L-arginine selectively inhibited Ca2+/calmodulin-dependent
      NO synthesis, with an IC50 of 0.55 microM in brain versus 184 and 258 microM in
      macrophages and vascular smooth muscle cells, respectively. In contrast, NG-amino
      L-homoarginine blocked NO production by all of the cell types examined, with IC50
      values ranging from 6.6 to 26 microM. Both inhibitors were active in an in vivo
      model of endotoxic shock.

PMID- 1382018
TI  - Felodipine. A review of the pharmacology and therapeutic use of the extended
      release formulation in cardiovascular disorders.
AB  - Felodipine is a vascular-selective, dihydropyridine calcium antagonist previously
      investigated as a conventional tablet formulation administered twice daily. More
      recently considerable experience has been gained with an extended release (ER)
      formulation which has the convenience of once daily administration. Felodipine ER
      has been well studied in patients with essential hypertension. As monotherapy in
      mild to moderate essential hypertension, felodipine ER is at least as effective
      in reducing blood pressure as other calcium antagonists, beta-blockers, diuretics
      and ACE inhibitors, with some results favouring felodipine ER at a statistically
      significant level at the dosages used. It is also effective combined with
      controlled release metoprolol or enalapril in patients with mild to moderate
      essential hypertension. In patients with more severe forms of essential
      hypertension uncontrolled by beta-blocker and/or diuretic therapy, felodipine ER
      was effective as an 'add-on' therapy in placebo-controlled trials, and, at the
      dosages used, more effective than either sustained release nifedipine or
      nitrendipine. Felodipine produces effective control of blood pressure without
      negative effects on cardiac performance. In addition to its antihypertensive
      action, results suggest that felodipine therapy is associated with significant
      regression of left ventricular hypertrophy. Furthermore, it appears suitable for
      use in patients with concomitant diabetes, renal dysfunction or asthma, and is
      also being investigated for use in patients with congestive heart failure or
      angina pectoris. Felodipine ER is an effective drug for the treatment of all
      grades of essential hypertension, and can be used both as monotherapy and in
      combination with other antihypertensive agents. Further clinical experience
      should fully establish the long term tolerability of felodipine ER and
      consequently its place in therapy relative to other accepted antihypertensive
      drugs. However, with the convenience of once daily administration, felodipine ER
      is a worthwhile innovation in the treatment of hypertension.

PMID- 1382021
TI  - Nitric oxide releases acetylcholine in the basal forebrain.
AB  - In conscious rats, the basal forebrain was superfused through a push-pull cannula
      and the release of acetylcholine was determined in the superfusate. Superfusion
      with the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine, diminished
      the release of acetylcholine. Subsequent superfusion with the NO donor, 3
      morpholino-sydnonimine, enhanced the release of the neurotransmitter. It is
      concluded that endogenous NO enhances the release of acetylcholine from its
      neurons.

PMID- 1382022
TI  - Effect of a benzodiazepine (chlordiazepoxide) on a GABAA receptor from rat brain.
      Requirement of only one bound GABA molecule for channel opening.
AB  - Chlordiazepoxide (CDPX) enhanced the rate of chloride exchange mediated by the
      major GABAA receptor found on sealed native membrane vesicles from rat cerebral
      cortex. The initial rate constant for chloride exchange for this receptor, (JA),
      a measure of open channel, was determined from the progress of GABA-mediated
      influx of 36Cl-. The dependence of JA on GABA concentration was hyperbolic in the
      presence of CDPX (150 microM, sufficient to give maximum enhancement of chloride
      exchange rate) but sigmoid in its absence. Enhancement of channel opening (10
      fold at 0.3 microM GABA) decreased with increasing GABA concentration. The
      maximal response, above 1,000 microM GABA, was unaltered. The half-response
      concentration was reduced from 80 microM to 50 microM. CDPX alone caused no
      measurable 36Cl- exchange. In the presence of CDPX, channel opening occurred with
      only one bound GABA molecule, whereas in its absence, channel opening with two
      bound GABA molecules was much more favorable. This could not be direct allosteric
      modulation of the channel opening conformational change by binding of CDPX at
      effector sites, but could be explained by an additional change of the receptor on
      binding CDPX to give a closed state which gave channel opening mediated by a
      single GABA binding site. Another possibility is that CDPX could act at one of
      the channel opening binding sites without a postulated, second closed
      conformational state.

PMID- 1382023
TI  - Human interleukin-1 receptor antagonist is expressed in liver.
AB  - Using PCR and Northern blot analysis, an IL-1 receptor antagonist specific
      transcript was amplified from HepG2- and liver mRNA. cDNA clones coding for IL-1
      receptor antagonist were isolated from a liver cDNA library and sequence
      comparison revealed complete identity with the secreted, monocytic form of IL-1
      receptor antagonist.

PMID- 1382024
TI  - 1,4-Dihydropyridines modulate GTP hydrolysis by Go in neuronal membranes.
AB  - Several lines of evidence suggest that L-type Ca2+ channels (1,4-dihydropyridine
      receptors) are modulated by GTP-binding proteins. We have further examined this
      interaction by measuring the effect of 1,4-dihydropyridines on GTPase activity in
      brain membranes. Dihydropyridine agonists significantly increased GTPase,
      reflected by an increase in the maximal rate of GTP hydrolysis, without affecting
      the affinity for GTP or the binding of a non-hydrolysable analogue of GTP. The
      stimulating effect on GTPase was abolished by antisera raised against Go alpha
      but not Gi alpha. L-type Ca2+ channels may act as endogenous GTPase activating
      proteins (GAPs) to stimulate GTP hydrolysis by Go.

PMID- 1382026
TI  - Identification of assembled epitopes on the alpha-subunit of human follicle
      stimulating hormone.
AB  - In order to characterize further the antigenic structure of human follitropin
      (hFSH), BALB/c mice were immunized with hFSH and anti-hFSH monoclonal antibodies
      (mAbs) were generated. The hFSH subunit specificity of the mAbs was assessed by a
      solid-phase enzyme-linked immunosorbent assay (ELISA) and a solution-phase
      radioimmunoassay (RIA), each using hFSH, hFSH alpha, and hFSH beta. Five mAbs
      bound hFSH and hFSH alpha in the ELISA and the RIA. In addition, some mAbs
      recognized hFSH beta, albeit to a much lower degree, as demonstrated by
      displacement of [125I]hFSH binding to the mAbs by hFSH beta, in the solution
      phase RIAs. Next, synthetic peptides corresponding to the hFSH alpha-subunit
      sequence were used to identify sequences specific to the epitopes of each of the
      five mAbs. Using this epitope mapping strategy, two assembled epitopes were
      identified. mAbs 3A and 4B distinguish one discontinuous epitope comprised
      minimally of sequences alpha-16-21 and alpha-66-92, whereas mAbs 5F and 2E
      distinguish a second discontinuous epitope comprised minimally of sequences alpha
      40-50 and alpha-66-72.

PMID- 1382025
TI  - Glucagon-like peptide-1(7-37)/(7-36)amide is a new incretin.
AB  - Glucagon-like peptide-1 (GLP-1) is the main product of the intestinal processing
      of proglucagon. It is released from the intestinal K-cells into the circulation
      in response to the oral ingestion of food. At the pancreatic beta cell GLP-1 is a
      potent insulin secretagogue in the presence of elevated glucose levels, defining
      glucagon-like peptide-1 as a new incretin. Its action is mediated by specific
      receptors coupled to the adenylate cyclase system by a stimulatory G-protein.
      Finally, glucagon-like peptide-1 stimulates proinsulin gene expression and it is
      thus involved at several levels in the regulation of insulin synthesis and
      secretion.

PMID- 1382027
TI  - Effects of calcitonin on human trophoblastic cells in culture: absence of
      autocrine control.
AB  - The purpose of this work was to investigate the effects of calcitonin (CT) on
      trophoblastic cells with respect to cAMP levels and human chorionic gonadotrophin
      (hCG) secretion in cultured cells from first-trimester and term placentas and in
      a choriocarcinoma cell line (JEG-3). The expression of the CT gene was
      investigated to elucidate a putative autocrine control of CT during pregnancy.
      The addition of salmon CT (10(-10) M and above) resulted in concentration
      dependent increases in cAMP secretion by normal trophoblastic cells from term and
      first-trimester placentas. Moreover, CT was found to increase cAMP secretion
      preferentially in completely differentiated cells, i.e. after 4-7 days in
      culture. Addition to the culture medium of JEG-3 cells slightly increased cAMP
      secretion only at a concentration of 10(-8) M. The basal level of hCG in the
      medium was found to be higher in the first-trimester than in the term trophoblast
      culture, but salmon CT induced an increase in hCG secretion by term placenta
      cells only. CT gene expression in our experimental model was investigated to
      elucidate a putative autocrine control of CT action during pregnancy. It was not
      found to be expressed in syncytiotrophoblast cells from either first-trimester or
      term placenta cells by the method used. Our data demonstrate the absence of
      autocrine control of CT effects in trophoblastic cells, and suggest that CT is
      likely to exert its effect preferentially on differentiated cells.

PMID- 1382028
TI  - Topographic analysis of human follicle-stimulating hormone-beta using anti
      peptide antisera.
AB  - The purpose of this study was to identify peptide sequences of human follicle
      stimulating hormone-beta (hFSH beta) which are accessible subsequent to
      association with hFSH alpha in heterodimeric hFSH. Antisera were raised against
      synthetic peptides (Abpep) corresponding to hFSH beta sequences 1-20, 16-36, 33
      53, 49-67, 66-85, 81-100 and 98-111. The topography of hFSH beta was studied by
      testing the binding of these antisera to hFSH beta and hFSH captured by
      monoclonal antibodies (MAb) in an enzyme-linked immunosorbent assay (ELISA). When
      hFSH and hFSH beta were captured by the same MAb, binding of Ab16-36, Ab33-53,
      Ab81-100 and Ab98-111 to hFSH was significantly lower compared to hFSH beta.
      However, compared to other Abpep, binding of Ab35-53 to hFSH was strong. Similar
      results were obtained when hFSH was captured by an alpha-specific MAb (10.3A6).
      Using 10.3A6, it was also possible to demonstrate significant binding of Ab49-67
      to hFSH. The data suggests that residues in regions 33-53 and 49-67 of hFSH beta
      appear to be accessible in the heterodimeric hFSH in addition to the glycosylated
      region of 1-15. Regions 16-36, 33-53, 81-100 and 98-111 of hFSH beta appear to
      contain subunit contact-associated sequences which are either masked or
      structurally altered subsequent to association with hFSH alpha in the
      heterodimeric hFSH.

PMID- 1382029
TI  - [Liver transplantation and hepatitis B virus. Some reasons to advance].

PMID- 1382030
TI  - A separating method for quantifying mucus glycoprotein localized in the different
      layer of rat gastric mucosa.
AB  - A method was devised for separating rat gastric mucosa into three layers each
      containing a different mucin species. The mucus gel (first layer) was removed by
      stirring the gastric mucosa in a solution of phosphate-buffered saline containing
      2% N-acetylcysteine. The surface mucosa (second layer), rich in surface mucus
      cells, was then separated from the deep mucosa (third layer) containing mucus
      neck cells, by scraping with forceps. The effectiveness of this method was
      confirmed by light microscopical observation after GOCTS-PCS (dual staining by
      the galactose oxidase-cold thionin Schiff method and paradoxical concanavalin A
      method) and AB-PAS staining (dual staining with alcian blue and the periodic acid
      Schiff method). The fixed specimen of scraped mucus and cell debris was rich in
      AB-PAS and GOCTS positive mucus, but was hardly stained by PCS, indicating mucus
      derived from surface mucus cells to have been efficiently recovered from this
      preparation. The residual mucosa could be stained by PCS but hardly at all by AB
      PAS or GOCTS. The lyophilized powder specimens obtained from the three different
      layers of rat gastric mucosa were used to extract and quantify mucus glycoprotein
      (mucin). This was done to examine changes in mucin content in the three layers of
      gastric mucosa one hour following the oral administration of 20% ethanol or 0.35
      N hydrochloric acid, both mild irritants. Mucin content was noted to
      significantly increase in the first layer but hardly at all in the second layer.
      In the third layer, it decreased significantly by 0.35 N hydrochloric acid, but
      changed only slightly by 20% ethanol administration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382032
TI  - PCNA staining and its problems in gastrointestinal tract.

PMID- 1382031
TI  - Overlap and discrepancy between tests for anti-C100, anti-GOR and anti-CP9 in
      patients with chronic liver disease and inhabitants in Saga, Japan.
AB  - The authors evaluated the clinical significance of anti-C100, anti-GOR and anti
      CP9 in hepatitis C virus (HCV)-related liver disease in two populations: 459
      healthy subjects and 385 patients with chronic liver disease (CLD). Previously we
      reported high rates of mortality and morbidity (5.3%) of CLD in subjects in Saga,
      Japan. This was ascribed to the high prevalence (10.8%) of anti-HCV among
      randomized populations, as detected by the C100 ELISA test system, as compared
      with a finding of 2-3% in Japanese blood donors in the same decade. The incidence
      of anti-C100, anti-GOR and anti-CP9 detected by ELISA test system in the healthy
      population currently surveyed was 17.0%, 19.2% and 32.0% respectively, as
      compared with 75.3%, 60.3% and 73.0% respectively, in those with CLD. The
      incidence of positivity for at least one of the three antibodies was high (36.4%)
      among healthy subjects, and even higher (86.5%) among the patients with CLD. In
      the healthy subjects, incidence of positivity increased with age. The healthy and
      CLD populations differed in the proportion of cases positive for all three
      antibodies vs. those positive for at least one antibody: healthy subjects,
      52/167, 31.1%, vs. CLD patients, 197/333, 59.2%; P less than 0.01. Among the anti
      C100-positive healthy cases, these was a significantly high level of AST, ALT,
      ZTT and gamma GTP compared with negative cases, with or without anti-GOR and anti
      CP9 (P less than 0.01-0.05). These observations suggest that the presence of anti
      C100 may be related to the active state of HCV-related liver disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1382033
TI  - Comparative sequence analyses of the 16S rRNA genes of Lactobacillus minutus,
      Lactobacillus rimae and Streptococcus parvulus: proposal for the creation of a
      new genus Atopobium.
AB  - 16S rRNA gene sequencing was performed on the species Lactobacillus minutus,
      Lactobacillus rimae and Streptococcus parvulus in order to clarify their
      taxonomic position. Based on comparative sequence analyses these organisms
      represent a hitherto unknown line of descent within the lactic acid group of
      bacteria for which a new genus, Atopobium gen. nov., is proposed.

PMID- 1382034
TI  - Effect of human chorionic gonadotropin (hCG) on reverse transcriptase activity in
      HIV-1 infected lymphocytes and monocytes.
AB  - The majority of infants born to HIV-positive mothers are not infected in utero,
      suggesting that the pregnancy factors produced by fetal trophoblasts may provide
      protection against HIV-1 infection. Except for steroid female hormones, little is
      known of other pregnancy factors that may regulate either resistance or
      susceptibility to HIV-1. Human chorionic gonadotropin (hCG)--the major
      glycoprotein produced by the placental trophoblast throughout the pregnancy--was
      tested on reverse transcriptase activity in HIV-infected ACH-2 lymphocytes and U1
      monocytes. The results suggest that low non-cytotoxic doses of hCG (0.01-1.0 IU
      range) may inhibit viral replication in maternal blood cells.

PMID- 1382035
TI  - Arg276 of GseA, a Chlamydia trachomatis Kdo transferase, is required for the
      synthesis of the chlamydial genus-specific epitope in Escherichia coli.
AB  - GseA is an enzyme from Chlamydia trachomatis that can catalyse the addition of
      three 3-deoxy-D-manno-octulosonic acid (Kdo) residues onto lipid A precursors.
      GseA is similar, and in a few stretches identical, in its amino acid sequence to
      KdtA, an Escherichia coli Kdo transferase. In this study we altered an amino acid
      of GseA in a region that is identical between GseA and KdtA to test its
      importance in the structure or catalytic activity of GseA. We found that when
      Arg276 was changed to Lys, Ile or Ser, GseA activity was lost, suggesting an
      enzymatic role for this amino acid residue.

PMID- 1382036
TI  - [Microcephalic children without mental retardation].
AB  - 8 microcephalic children, mean age 3.06 years, with head circumferences -3.5 SD
      to -6 SD, achieved IQ scores of 79-115 on the Thermann, WPPSI, WISC-R, and/or
      Columbia tests. They had no dysmorphic features nor congenital anomalies, and
      their fundi were normal. 7 had congenital microcephaly, associated with proven
      autosomal dominant heritage in 3, 1 had suspected autosomal recessive heritage, 1
      had intrauterine growth retardation (overall smallness), 1 had cerebral palsy,
      and in 1 there was an unknown prenatal cause. 6 of these children had 1 or 2
      developmental disabilities, including neurosensory deafness, cerebral palsy,
      short attention span, perceptual dysfunctions, and learning disability.
      Microcephaly, most probably secondary to malnutrition in early infancy, was
      diagnosed in 1 child without developmental disabilities. However, our data
      support the concept that some microcephalic children with significantly small
      head circumference, who function without mental retardation, have a high
      incidence of other developmental disabilities.

PMID- 1382037
TI  - [Evans syndrome in a child].
AB  - A Bedouin girl, aged 2 3/12, was first seen at the age of 9 months for sequential
      onset of Coombs-positive hemolytic anemia and immune thrombocytopenia.
      Comprehensive laboratory workup revealed no underlying disease. Evans' syndrome,
      relatively rare in childhood, was diagnosed and corticosteroid therapy initiated.
      She responded well and normal hemoglobin and thrombocyte counts were achieved
      within a month. All attempts at tapering-off the dose of corticosteroids resulted
      in relapses, until high-dose intravenous gamma-globulin was given.

PMID- 1382038
TI  - Research in child language disorders: what do we know and where are we going?
AB  - Advances in understanding the nature of language impairment in children over the
      past decade have been abundant. In this paper, several recurring hypotheses about
      the nature of the clinical disorder of language impairment in children and
      underlying etiologies are explored and the ways in which we are moving forward in
      our understanding of them are considered. Specifically, in the first part, the
      recent thinking on the nature of specific language impairment as a clinical
      concept is examined. Characteristics of the population are reviewed and the
      search for causation is considered. Literature on the relations between language
      and cognition and between language and social cognition is probed for
      contributions to our understanding of developmental disorders of language. Two
      areas in which we have seen marked progress and which hold promise for
      development in the coming decade are the focus of the second part of the paper.
      The focal areas are: computer-assisted language sample analyses and
      neurophysiological contribution to understanding language impairment in children.
      Thoughts about future directions for work in the area of developmental disorders
      of language are offered in conclusion.

PMID- 1382039
TI  - Inhibition of the alternative pathway of complement by glomerular chondroitin
      sulphate proteoglycan.
AB  - Cultured rat glomerular epithelial cells (GEC) synthesize and secrete a
      complement inhibitory chondroitin sulphate B proteoglycan (termed GCRF). As
      proteoglycans and their component glycosaminoglycans may affect several different
      steps of complement activation, the functional properties of GCRF were
      investigated in this study. GCRF inhibited preformed alternative pathway
      convertases (C3bBbP), but did not substantially accelerate their decay. In
      contrast to other polyanions, GCRF did not affect the activity of human or rat
      factor H, nor did it inhibit the terminal complement proteins. GCRF inhibited the
      effect of decay-accelerating factor (DAF) on C3bBbP when the two were incubated
      together and DAF was in excess, but it did not affect the decay of DAF of
      classical pathway convertases. However, when DAF was first incorporated into the
      erythrocyte membrane, the effect of GCRF on C3bBbP was additive to that of DAF.
      Thus, GCRF inhibits the activity of C3bBbP and blocks the action of DAF, but not
      that of factor H, perhaps by binding to factor B in the alternative pathway
      convertase.

PMID- 1382040
TI  - Enhancement of trinitrophenyl-specific humoral response to TNP proteins as the
      result of carrier chlorination.
AB  - Trinitrophenyl (TNP)-specific humoral response was tested after immunization with
      TNP-protein conjugates composed of either native proteins or proteins modified by
      chlorination. Significant enhancement of the hapten-specific response was
      observed as a result of carrier chlorination. This effect was dose dependent and
      affected mainly T-helper-cell activation. Since stimulated neutrophils chlorinate
      in vivo proteins, we propose that they take part in the induction phase of immune
      response by facilitation of antigen processing and/or presentation.

PMID- 1382042
TI  - Extracellular matrix protein tenascin-like gene found in human MHC class III
      region.

PMID- 1382041
TI  - Aphidicolin-induced proliferative arrest of murine mast cells: morphological and
      biochemical changes are not accompanied by alterations in cytokine gene
      induction.
AB  - Investigations of mast cell biology have often used immortalized cultured cells
      which are continuously proliferating. In vivo, however, only 2% or fewer tissue
      mast cells are actively dividing. We used aphidicolin, an inhibitor of DNA
      polymerase to induce a proliferative arrest of murine mast cells characterized by
      an inhibition of cell division and thymidine incorporation, with accumulation of
      cells in G1 and early S phase of the cell cycle. Uridine incorporation and cell
      viability were not significantly impaired. DNA synthesis and cell division both
      resumed rapidly upon removal of the drug. Morphometric analysis demonstrated that
      cell size, granule size, and number of granules per cell were all increased in
      aphidicolin-treated cells. Proliferative arrest also produced a 14-fold increase
      in cellular histamine content, but did not alter the proteoglycans synthesized by
      the cell. The level of c-myc mRNA was reduced in aphidicolin-arrested cells, but
      returned to the level observed in untreated cells within 1 hr of removal of the
      drug. In contrast, the constitutive steady-state RNA levels of tumour necrosis
      factor-alpha (TNF-alpha), B2-microglobulin, actin, and the c-Ha-ras and c-fes
      protooncogenes were not altered. Aphidicolin-induced proliferative arrest did not
      prevent the induction of TNF-alpha, interleukin-6 (IL-6) and c-fos genes in
      response to calcium ionophore. Both the magnitude and induction kinetics of these
      messages were similar in aphidicolin-treated and untreated cells. We conclude
      that proliferative arrest results in morphological and biochemical changes
      suggestive of cellular maturation, but inhibition of cell division alone is not
      sufficient to alter mast cell phenotype. Although optimal c-myc expression
      appears to require active proliferation, cytokine gene induction can occur in non
      dividing cells. These data suggest that the proliferative quiescence of in vivo
      mast cells should not preclude their involvement in biological events via
      elaboration of multi-functional cytokines.

PMID- 1382043
TI  - In vitro effects of drugs on production of mucins in rabbit tracheal epithelial
      cells expressing mucin gene: a model system for studying upper airway respiratory
      diseases.
AB  - Rabbit tracheal epithelial cells, cultured on collagen-coated dishes in serum
      free and hormone-supplemented medium, were found to incorporate [3H]glucosamine
      into high-molecular-weight components that were secreted in the medium. The
      chemical analysis of the secreted products resulted in a profile that resembled
      that of mucous glycoproteins (mucins). When examined by dot blot analysis, the
      total RNA isolated from these cells hybridized to an antisense 30-mer
      oligonucleotide corresponding to a rat intestine mucin peptide sequence,
      indicating that mucin gene was expressed in these cell lines. Lung and liver
      tissues of rabbit did not express this gene. Transmission electron microscopy
      exhibited secretory granules in these cells. The incorporation of [3H]glucosamine
      into mucins was inhibited by three aryl-N-acetyl-galactosaminides and a chemical
      carcinogen, N-nitroso-N-ethyl urea, whereas 5-azacytidine enhanced the
      proliferation of cells as well as the radiolabeling of mucins. Parasympathetic
      agent (pilocarpine), cholinergic antagonist (atropine), and beta-adrenergic
      agonist (isoproterenol) alone have little effect on the secretion of mucins. The
      cholinergic agonist, methacholine, was found to increase the production of mucins
      and addition of atropine to the medium before methacholine blocked this
      stimulation. Histamine was found to stimulate mucin production in these cells.

PMID- 1382044
TI  - Diminished epinephrine excretion in genetically obese (ob/ob) mice and monosodium
      glutamate-treated rats.
AB  - While numerous studies have examined sympathetic nervous system activity in
      experimental obesity, adrenal medullary function in this condition has received
      less attention. The experiments described herein evaluated adrenal medullary
      secretion by measurement of urinary epinephrine (Epi) excretion in genetically
      obese (ob/ob) mice and monosodium glutamate (MSG)-treated rats. In both male and
      female ob/ob mice Epi excretion was reduced 42% (P less than 0.015) and 47% (P
      less than 0.025), respectively, despite higher rates of urine output and
      excretion for other amines in obese compared to lean animals. In a similar
      fashion, urinary Epi was also lower in MSG-treated adult rats than in untreated
      controls; this reduction was out of proportion to group differences in body
      weight or excretion of other catecholamines. Administration of D,L-fenfluramine
      to mice, or dietary protein supplementation in rats, increased Epi excretion to
      the same extent in obese and lean animals. These findings indicate that secretion
      of Epi by the adrenal medulla is diminished, but is normally responsive to
      stimulation in these two models of animals obesity, and are thus consistent with
      accumulating evidence of a functional impairment in adrenal medullary secretion
      in animal and human obesity.

PMID- 1382045
TI  - Transferrin receptor expression by retinal pigment epithelial cells in
      proliferative vitreoretinopathy.
AB  - Immunotoxins directed against a membrane marker of cell proliferation,
      transferrin receptor, were investigated to inhibit the growth of retinal pigment
      epithelial (RPE) cells in proliferative vitreoretinopathy (PVR). We undertook an
      immunocytological study in specimens of vitreous, subretinal fluid, and
      epiretinal membranes from patients with PVR to address the expression of
      transferrin receptor by proliferating pigment epithelial cells during the course
      of PVR and in normal human ocular structures. Thirty four specimens of vitreous
      and subretinal fluid, as well as seven epiretinal membranes, were
      immunocytologically examined using monoclonal antibodies to transferrin receptor.
      They showed a strong expression of this marker by a large majority of the cells
      in these two periretinal fluids (mean percentages 80 and 91% in vitreous and
      subretinal fluid, respectively). In contrast, only a few cells within epiretinal
      membranes were found to express transferrin receptor. In normal human eye
      sections conjunctival and corneal epithelial cells, subcapsular epithelium of the
      lens strongly expressed transferrin receptor, whereas RPE cells remained negative
      to antitransferrin receptor antibodies. A few iris or ciliary pigment epithelial
      cells reacted weakly. Thus, this study shows that most intravitreal and
      subretinal fluid proliferating cells strongly express transferrin receptor on
      their surface. Also confirmed is that immunotoxins to this membrane antigen could
      constitute potentially useful therapeutic agents in PVR.

PMID- 1382046
TI  - Lithium inhibits substance P and vasoactive intestinal peptide-induced
      relaxations on isolated porcine ophthalmic artery.
AB  - Lithium is currently a major drug used as a treatment for affective disorders and
      cluster headache, among other conditions. Its mechanism of action remains
      unknown. The trigeminovascular system may be involved in the pathophysiology of
      cluster headache and related diseases by liberating neuropeptides such as
      substance P (SP) and calcitonin gene-related peptide (CGRP) in the eye-forehead
      region. The objective of this study was to investigate whether or not a low
      concentration of lithium may interfere with peptidergic neuro-transmission at
      this level. Vasoactive intestinal peptide (VIP), SP, CGRP, capsaicin, and SP+CGRP
      concentration-response relaxation curves were obtained in the presence and
      absence of 2 x 10(-4) M lithium in isolated porcine ophthalmic arteries. Lithium
      inhibited the SP and VIP, but not the CGRP responses. Capsaicin-(a neurotoxin
      causing release of stored sensory neuropeptides) induced relaxations were
      partially inhibited by lithium. It is concluded that lithium may interfere with
      SP- and VIP-induced relaxation. If SP and VIP are of pathogenic significance in
      cluster headache, lithium may possibly work by counteracting unwanted effects of
      such peptides.

PMID- 1382047
TI  - Reoxygenation in the RIF-1 tumor after chemotherapy.
AB  - The proportion of hypoxic cells in the RIF-1 tumor was observed for 24 hr after
      treatments with bleomycin, cisplatin, cyclophosphamide, and mitomycin C. The
      assays were based upon the paired survival curve method for determining the
      hypoxic fraction using irradiation of aerobic and artificially hypoxic tumors. It
      was observed that at 1/2 hr after bleomycin, hypoxic fraction was elevated but
      returned to baseline levels by 2 hr. Following cisplatin, hypoxic fraction did
      not rise above baseline. However, after cyclophosphamide, hypoxic fraction was
      elevated and did not return to baseline over the 24-hr observation period of this
      study. At 1/2 hr after mitomycin treatment, the hypoxic fraction was raised but
      within 1 hr returned to baseline. These results indicate that tumor reoxygenation
      varies after different drug treatments and that the determination of drug
      specificity for aerobic versus hypoxic cells may be strongly biased by the choice
      of the time after treatment for making the determination.

PMID- 1382048
TI  - Location of motoneurons innervating the middle ear muscle of the chicken, (Gallus
      domesticus).
AB  - The motoneuron pool for the musculus columellae, the avian equivalent to the m.
      stapedius, was identified by retrograde labeling with WGA-HRP. It consists of a
      discrete group of approximately 65 neurons located along the dorsolateral border
      in the ventral subnucleus of the facial nuclear complex. Other facial motoneurons
      were only labeled when diffusion of the tracer into neighbor structures was not
      excluded. The dorsal subnucleus of the facial nerve innervates the m. depressor
      mandibulae.

PMID- 1382049
TI  - Ca(2+)-activated nonselective cation, maxi K+ and Cl- channels in apical membrane
      of marginal cells of stria vascularis.
AB  - Patch clamp recordings on the apical membrane of marginal cells of the stria
      vascularis of the gerbil were made in the cell-attached and excised
      configuration. Marginal cells are thought to secrete K+ into and absorb Na+ from
      endolymph. Four types of channel were identified; the most frequently observed
      channel was a small, nonselective cation channel which was highly similar to that
      found in the apical membrane of vestibular dark cells (Marcus et al., (1992) Am.
      J. Physiol. 262, C1423-C1429). The small nonselective cation channel was equally
      conductive (26.7 +/- 0.3 pS; N = 49) for K+, Na+, Rb+, Li+ and Cs+, 1.6 times
      more permeable to NH4+, but not permeable to Cl-, Ca2+, Ba2+ or N-methyl-D
      glucamine. This channel yielded linear current-voltage relations which passed
      nearly through the origin (intercept: -2.2 +/- 0.4 mV, N = 49) when conductive
      monovalent cations were present on both sides of the membrane in equal
      concentrations. Channel activity required the presence of Ca2+ at the cytosolic
      face but not the extracellular (endolymphatic) face; there was essentially no
      activity for cytosolic Ca2+ less than or equal to 10(-7) M Ca2+ and full activity
      for greater than or equal to 10(-5) M. Cell-attached recordings had a conductance
      of 28.6 +/- 2.2 pS (N = 6) and a reversal voltage of -2.2 +/- 5.2 mV (N = 3)
      which was interpreted to reflect the intracellular potential of marginal cells
      under the present conditions. The three other types of channel were a Cl- channel
      (approximately 50 pS; N = 2), a maxi-K+ channel (approximately 230 pS; N = 1),
      and another large channel, probably cation nonselective (approximately 170 pS; N
      = 1). The 27 pS nonselective cation channel may be involved in K+ secretion and
      Na+ absorption under stimulated conditions which produce an elevated
      intracellular Ca2+; however, consideration of the apparent channel density in
      relation to the total transepithelial K+ flux suggests that these channels are
      not sufficient to account for K+ secretion.

PMID- 1382050
TI  - Muscle sarcomere lesions and thrombosis after spaceflight and suspension
      unloading.
AB  - Spaceflight (flight) and tail suspension-hindlimb unloading (unloaded) produced
      significant decreases in fiber cross-sectional areas of the adductor longus (AL),
      a slow-twitch antigravity muscle. However, the mean wet weight of the flight AL
      muscles was near normal, whereas that of the suspension unloaded AL muscles was
      significantly reduced. Interstitial edema within the flight AL, but not in the
      unloaded AL, appeared to account for this apparent disagreement. In both
      experimental conditions, the slow-twitch oxidative fibers atrophied more than the
      fast-twitch oxidative-glycolytic and fast-twitch glycolytic fibers.
      Immunostaining showed that slow-twitch oxidative fibers expressed fast myosin,
      producing hybrid fibers containing slow and fast myosin isoforms. Two-dimensional
      gel electrophoresis of flight AL muscles revealed increased content of fast
      myosin light chains and decreased amounts of slow myosin light chains and fatty
      acid-binding protein. In the flight AL, absolute mitochondrial content decreased,
      but the relatively greater breakdown of myofibrillar proteins maintained
      mitochondrial concentration near normal in the central intermyofibrillar regions
      of fibers. Subsarcolemmal mitochondria were preferentially lost and reduced below
      normal concentration. Elevated fiber immunostaining for ubiquitin conjugates was
      suggestive of ubiquitin-mediated breakdown of myofibrillar proteins. On return to
      weight bearing for 8-11 h, the weakened atrophic muscles exhibited eccentric
      contraction-like lesions (hyperextension of sarcomeres with A-band filaments
      pulled apart and fragmented), tearing of the supporting connective tissue, and
      thrombosis of the microcirculation. Segmental necrosis of muscle fibers,
      denervation of neuromuscular junctions, and extravasation of red blood cells were
      minimal. Lymphocyte antibody markers did not indicate a significant immune
      reaction. The flight AL exhibited threefold more eccentric-like lesions than the
      unloaded AL; the high reentry G forces experienced by the flight animals, but not
      the unloaded group, possibly accounted for this difference. Muscle atrophy
      appears to increase the susceptibility to form eccentric contraction-like lesions
      after reloading; this may reflect weakening of the myofibrils and extracellular
      matrix. Microcirculation was also compromised by spaceflight, such that there was
      increased formation of thrombi in the post-capillary venules and capillaries.
      This blockage led to edema by 8-11 h after resumption of weight bearing by the
      COSMOS 2044 rats. The present findings indicate that defective microcirculation
      most likely accounted for the extensive tissue necrosis and microhemorrhages
      observed for COSMOS 1887 rats killed 2 days after landing.

PMID- 1382051
TI  - Skeletal muscle atrophy in response to 14 days of weightlessness: vastus
      medialis.
AB  - The vastus medialis (VM) from rats after 14 days of microgravity on COSMOS 2044
      (F) was compared with VM from tail-suspended hindlimb-unloaded rats (T) and
      ground controls, including vivarium (V), synchronous (S), and basal (B) animals.
      The VM is composed chiefly of fast-twitch fibers; however, it contains a deep
      portion closer to the bone with mixed slow- and fast-twitch fibers. In the mixed
      fiber portion, type I and II fiber areas were significantly reduced in F animals.
      In the homogeneous portion with chiefly fast-twitch fibers, F rats also showed
      reductions in cross-sectional areas compared with T, V, and B but not S rats.
      Fiber densities (fibers/mm2) were greatest in VM from F rats. Capillary density
      changes paralleled fiber density changes. F animals have significantly greater
      density of capillaries in the mixed-fiber portion. Concentrations of protein,
      RNA, and DNA were highest in V controls, whereas F rats had the lowest level of
      total RNA. Lactate dehydrogenase activity, one measure of anaerobic capacity, was
      greater in F than in S rats. Citrate synthase activity, a measure of oxidative
      capacity, showed no significant differences between groups. Although triglyceride
      stores of VM were greater in F than in T rats, there were no significant
      differences from any of the control groups. It was concluded that VM wet weights
      may be a less sensitive measure of atrophy than the fiber area measurements.
      Fiber area decreases and fiber density increases in F animals were quantitatively
      comparable to those in soleus and extensor digitorum longus after 7 days of
      weightless flight in Spacelab 3. Our results suggest that VM shows measurable
      responses to weightlessness.

PMID- 1382052
TI  - Functional analysis of novel selective mutants of the reverse transcriptase of
      human immunodeficiency virus type 1.
AB  - We have generated by site-directed mutagenesis plasmids that induce the synthesis
      of specific mutants of the reverse transcriptase (RT) of human immunodeficiency
      virus type 1 (HIV-1). These recombinant mutants of HIV-1 RT, designed on the
      basis of our previous studies of HIV-1 and HIV-2 RTs, were analyzed for structure
      function relationship by assessing their RNA-dependent and DNA-dependent DNA
      polymerase as well as the ribonuclease H activities. Three groups of mutants were
      studied. 1) We have investigated the importance of the only two sets of highly
      conserved double prolines found in the sequence of HIV-1 RT. The results indicate
      that the conversion of either one or both prolines (at positions 225 and 226) to
      threonines have no significant effect on all catalytic activities of the enzyme.
      The mutants in which prolines 419 and 420 were individually modified to
      threonines exhibit full activities, whereas the double proline 419/420 mutant
      lost most of its RNase H activity (although the DNA polymerase function was fully
      retained). 2) We have deleted phenylalanine 346 from HIV-1 RT, which is absent in
      wild type HIV-2 RT. This mutant of HIV-1 RT lost practically all catalytic
      activities. 3) A mutant of HIV-1 RT in which a cysteine residue substituted for
      alanine 446, was found to be slightly hyperactive for both DNA polymerase and
      RNase H activities.

PMID- 1382053
TI  - The 10 S BC-1 ribonucleoprotein particle contains identifier sequence-binding
      proteins that interact with an array of GCAAG/CTTGC motifs between split promoter
      sequences for RNA polymerase III.
AB  - BC-1 RNA is a brain-specific small RNA transcript of identifier sequences present
      in the somas and dendrites of neurons. We recently reported that the RNA is
      complexed with a protein(s) to form a 10 S ribonucleoprotein particle (Kobayashi,
      S., Goto, S., and Anzai, K. (1991) J. Biol. Chem. 266, 4726-4730). We demonstrate
      here that this 10 S BC-1 ribonucleoprotein particle contains a DNA-binding
      protein(s) (Bp-1 protein) capable of interacting with a region between split
      promoter sequences for RNA polymerase III within the identifier sequences. The
      region has short inverted repeats: a perfect octanucleotide repeat
      (GCGCTTGCCTAGCAAGCGC) and an imperfect heptanucleotide repeat
      (GCCTAGCAAGCGCAAGGC), each of which contains a GCAAG/CTTGC motif. We also
      demonstrate that the binding of this protein either to the array of pentamer
      motifs or to BC-1 RNA is mutually exclusive. The molecular masses of photo-cross
      linking adducts of Bp-1 protein to a 32P-labeled GCAAG/CTTGC motif-specific probe
      were estimated to be about 31 and 36 kDa, indicating that two species of Bp-1
      proteins may be present in the brain.

PMID- 1382054
TI  - Functional homogeneity of the non-mitochondrial Ca2+ pool in intact mouse
      lacrimal acinar cells.
AB  - In the absence of extracellular Ca2+, treatment of mouse lacrimal acinar cells
      with maximal concentrations of methacholine released Ca2+ from intracellular
      stores. No additional Ca2+ was mobilized by subsequent application of the
      intracellular Ca(2+)-ATPase inhibitor, thapsigargin, the stable inositol 1,4,5
      trisphosphate ((1,4,5)IP3) analog, inositol 2,4,5-trisphosphate ((2,4,5)IP3) (by
      microinjection), or the Ca2+ ionophore, ionomycin. However, following prolonged
      activation of cells by methacholine in the presence of extracellular Ca2+, Ca2+
      accumulated into a pool which was released by ionomycin but not by thapsigargin.
      This latter accumulation was blocked by prior microinjection of ruthenium red,
      indicating that it represents mitochondrial uptake. In saponin-permeabilized
      lacrimal cells, two Ca(2+)-sequestering pools were detected: (i) a ruthenium red
      sensitive, thapsigargin-insensitive pool, presumed to be the mitochondria; and
      (ii) a ruthenium red-insensitive, thapsigargin-sensitive pool. Only the
      thapsigargin-sensitive pool accumulated Ca2+ at concentrations similar to those
      in unstimulated cells. The thapsigargin-sensitive Ca2+ pool was sensitive to
      (1,4,5)IP3; however, in contrast to findings in intact cells, only 44% of this
      pool was releasable by (1,4,5)IP3 or (2,4,5)IP3. These data indicate that, in
      intact lacrimal acinar cells, all exchangeable (ionomycin-sensitive) Ca2+
      residues in a pool which responds homogeneously to agonists, (1,4,5)IP3, and
      thapsigargin. Prolonged elevation of [Ca2+]i results in Ca2+ accumulation into a
      second, ruthenium red-sensitive pool, presumably mitochondria. Finally,
      permeabilization of the cells fragments the non-mitochondrial pool, resulting in
      two pools, one sensitive and one insensitive to (1,4,5)IP3.

PMID- 1382055
TI  - Analysis of a 43-kDa glycoprotein from the intracellular parasitic nematode
      Trichinella spiralis.
AB  - The L1 larvae of the parasitic nematode Trichinella spiralis invade skeletal
      muscle and initiate a process that has been interpreted to represent skeletal
      muscle dedifferentiation. In this process, the infected region of the muscle cell
      is converted into a unique structure, called the Nurse cell. The nematode T.
      spiralis can survive for tens of years within the cytoplasm of the Nurse cell and
      secretes proteins into the cytoplasm that are believed to play a role in
      mediating the Nurse cell formation or maintenance. We have cloned a cDNA encoding
      the T. spiralis-derived, 43-kDa secreted protein. Structural analysis of the
      predicted 344-amino acid sequence revealed an N terminally located signal peptide
      and a potential helix-loop-helix motif in the main body of the protein.
      Antibodies raised against the 43-kDa recombinant protein were used in
      immunocytolocalizations of T. spiralis-infected skeletal muscle sections. These
      antibodies strongly stained the Nurse cell nuclei and the nematode itself.
      Specific, though slightly weaker staining also occurred in the Nurse cell
      cytoplasm. In Western blots, the antibodies react with the 43-kDa protein but
      also detected at least two other T. spiralis-secreted proteins. DNA
      hybridizations reveal at least one additional 43-kDa-related sequence encoded in
      the T. spiralis genome. We conclude that either the 43-kDa protein and/or a
      closely related 43-kDa family member is secreted into the muscle and translocates
      to the muscle-derived nuclei. This model may provide insights into the mechanisms
      involved in Nurse cell formation.

PMID- 1382056
TI  - Lactoferrin specifically inhibits endocytosis of chylomicron remnants but not
      alpha-macroglobulin.
AB  - Our recently found nonlipoprotein inhibitor of chylomicron remnant uptake,
      lactoferrin, has been investigated in vivo and in vitro. Lipoprotein lipase
      extracted triglycerides from chylomicrons, doubly labeled with
      [3H]retinol/[14C]oleate, in the presence of lactoferrin normally. The subsequent
      uptake of remnants into liver was retarded considerably. In the intact rat,
      chylomicron remnants (CRs), predominantly labeled in the apoB48 moiety by 125I,
      were excluded from the hepatic endosomal compartment in the presence of
      lactoferrin as shown in subcellular fractionation studies of rat livers. In
      tissue culture, internalization of [125I]chylomicron remnants was inhibited in
      the presence of 14 pM lactoferrin by 70%. Upon removal of lactoferrin,
      internalization was rapidly restored. Protease digestion eliminated the
      inhibitory effect completely. Modification of arginine residues with
      cyclohexanedione reversibly removed the inhibitory potency of lactoferrin. We
      located by molecular modeling an alpha-helical segment in lactoferrin on the
      exposed surface of the molecule containing the sequence Arg-X-X-Arg-Lys-X-Arg,
      which resembles the receptor recognition structure in apolipoprotein E (apoE).
      This firmly established ligand correspondence with apoE, the candidate ligand for
      CR recognition by the receptor. Finally, the postulated second function of low
      density lipoprotein receptor-related protein, uptake of alpha-2-macroglobulin
      (alpha 2M) was found to be distinct from lipoprotein binding, since lactoferrin
      inhibited CR but not alpha 2M internalization. In addition, CR uptake was not
      affected by alpha 2M. We conclude that if a bifunctional receptor were to
      operate, its diverse functions were exerted by independently operating
      substructures. The results of our in vivo and cell culture experiments are,
      however, entirely compatible with the existence of two receptors as well.

PMID- 1382057
TI  - Ligand-independent oligomerization of natriuretic peptide receptors.
      Identification of heteromeric receptors and a dominant negative mutant.
AB  - Activation of many single-transmembrane receptors requires ligand-induced
      receptor oligomerization. We have examined the oligomerization of the atrial
      natriuretic peptide receptor, NPR-A, using epitope-tagged receptor in a co
      immunoprecipitation assay. Unlike other single-transmembrane receptors, NPR-A
      oligomerized in a ligand-independent fashion. Extracellular receptor sequences
      were both necessary and sufficient for oligomer formation. NPR-A was also able to
      oligomerize with the related natriuretic peptide receptor, NPR-B. A truncated NPR
      A lacking most of the cytoplasmic domain blocked activation of the full-length
      receptor, presumably through formation of an inactive heteromer. These results
      indicate that oligomerization of this single-transmembrane receptor is important
      for the transduction of a conformational change across the plasma membrane but
      are not consistent with models in which natriuretic peptide receptor
      oligomerization serves merely to bring intracellular domains together.

PMID- 1382059
TI  - An intramolecular DNA triplex is disrupted by point mutations associated with
      hereditary persistence of fetal hemoglobin.
AB  - Several investigators have suggested that secondary structures in DNA may be
      involved with physiologic gene regulatory processes in higher organisms. This
      hypothesis has been difficult to prove, however, since naturally occurring
      mutations that alter secondary DNA structures have not yet been identified. In
      this report, we describe a secondary DNA structure upstream from the human gamma
      globin genes; this structure is formed in a homopyrimidine-homopurine tract and
      is stabilized by acidic pH and negative supercoiling of plasmid DNA. Since this
      structure is asymmetrically cleaved by S1 nuclease, it probably contains a single
      stranded region and an intramolecular triplex. The single-stranded region is
      actually accessible for Watson-Crick base pairing with exogenous oligomers, a
      characteristic that permitted us to directly map the secondary DNA structure
      without additional chemical modifications of the supercoiled DNA. Five different
      point mutations just downstream from the single-stranded region are associated
      with hereditary persistence of fetal hemoglobin; four of these mutations
      dramatically reduce the stability of the secondary DNA structure, suggesting that
      these mutations alter formation of the intramolecular triplex by destabilizing
      critical Hoogsteen (triple-stranded) base pairs. These mutations may therefore
      represent a novel class of genetic defects that alter gene expression by changing
      the interaction of a critical regulatory molecule with a secondary DNA structure.

PMID- 1382058
TI  - Accelerated proliferation and interleukin-2 production of thymocytes by
      stimulation of soluble anti-CD3 monoclonal antibody in transgenic mice carrying a
      rabbit protein kinase C alpha.
AB  - Protein kinase C (PKC) has been believed to play an important role in the
      differentiation/proliferation of various kinds of mammalian cells. To analyze its
      function in living animals, we have established a transgenic mouse line carrying
      rabbit protein kinase C alpha cDNA under the control of the regulatory element of
      human CD2. Thymocytes of these transgenic mice overexpressed PKC alpha.
      Interestingly, the increase of PKC alpha was detected mainly in membrane
      fractions of transgenic thymocytes. Although the transgenic thymocytes did not
      show any distinct proliferative features in vivo, they displayed a unique
      property to extensively proliferate and produce interleukin-2 (IL-2) in response
      to the stimulation by a soluble form of anti-CD3 monoclonal antibody (mAb), an
      incomplete agonist for proliferation of normal thymocytes. Furthermore, co
      stimulation of the phorbol 12-myristate 13-acetate and anti-CD3 mAb intensely
      provoked the transgenic thymocytes to release IL-2. For the first time this
      result provided the direct evidence that PKC alpha translocated to the cell
      membrane of thymocytes works as an active second messenger of the T cell receptor
      CD3 complex-delivered signal for proliferation and IL-2 production.

PMID- 1382060
TI  - A novel 3-deoxy-D-manno-octulosonic acid transferase from Chlamydia trachomatis
      required for expression of the genus-specific epitope.
AB  - DNA cloned from Chlamydia trachomatis is able to direct the formation of the
      genus-specific lipopolysaccharide epitope of chlamydiae in enteric Gram-negative
      bacteria. We now demonstrate that a single C. trachomatis gene (gseA) is
      sufficient to impart this trait to Escherichia coli. The deduced amino acid
      sequence of gseA shows 23% identity (66% similarity) to kdtA, an E. coli gene
      that codes for a bifunctional enzyme catalyzing the addition of two 3-deoxy-D
      manno-octulosonic acid (Kdo) residues to lipid A precursors (Clementz, T., and
      Raetz, C. R. H. (1991) J. Biol. Chem. 266, 9687-9696). Extracts of E. coli
      expressing gseA transfer at least one additional Kdo unit from CMP-Kdo to
      precursors already bearing the two Kdo residues attached by the kdtA gene
      product. Introduction of gseA into an E. coli mutant with a thermolabile kdtA
      gene product endows cell extracts with the ability to transfer not only the third
      but also the first two Kdos to lipid A precursors, demonstrating that the C.
      trachomatis enzyme is at least trifunctional. Given the similarities of these two
      Kdo transferases and the essentiality of Kdo in Gram-negative bacteria,
      lipopolysaccharide biosynthesis may be a target for development of novel drugs
      effective against chlamydiae.

PMID- 1382061
TI  - Induction of endogenous myosin light chain 1 and cardiac alpha-actin expression
      in L6E9 cells by MyoD1.
AB  - Rat L6E9 muscle cells commit to terminal differentiation by forming a large
      muscle syncitia complete with the expression of a large number of muscle-specific
      contractile protein genes. To determine whether these cells, which fail to
      synthesize MLC (myosin light chain) 1 and cardiac alpha-actin, exhibit a
      deficiency in the expression of muscle determination genes, we measured
      expression of MyoD1, myogenin, Myf-5, and MRF-4. Results show these cells do not
      synthesize MyoD1, yet express the other myogenic determination genes. Transient
      expression of exogenous MyoD1 in these cells is sufficient to activate endogenous
      MLC 1 and cardiac alpha-actin mRNA synthesis during muscle differentiation.
      Previously undetected myosin heavy chain (MHC) isoforms (beta-MHC and perinatal
      MHC) are also transcribed at low levels in L6E9 muscle cells, and in MyoD1
      transfected L6E9 cells no change occurs in their expression. Furthermore,
      treatment with the demethylating agent 5-azacytidine activates expression of the
      endogenous MyoD1 gene in L6E9 cells and, subsequently, rescues deficiencies in
      their myogenic biochemical program. These results demonstrate that the endogenous
      MyoD1 gene in L6E9 cells is not defective and can be functionally activated.
      Also, the MyoD1 protein plays an essential role, which cannot be compensated by
      other known muscle determination proteins, in the induction of MLC 1 and cardiac
      alpha-actin expression.

PMID- 1382062
TI  - A bifunctional genetic regulatory element of the rat dopamine beta-hydroxylase
      gene influences cell type specificity and second messenger-mediated
      transcription.
AB  - Dopamine beta-hydroxylase, the enzyme which converts dopamine to norepinephrine,
      is expressed in a cell type-restricted pattern in neuroendocrine tissue. A
      segment of the rat gene containing 395 bases of 5'-flanking sequence regulates
      expression of a reporter gene in a cell type-selective pattern in mammalian cell
      cultures. Using deletion mutants of the 5'-flanking sequence, we have identified
      a 30-base genetic regulatory element, designated DB1, which enhances
      transcription from a heterologous promoter 5-20-fold in neuroendocrine cell
      lines. DB1-specific DNA-protein complexes are found in nuclear extracts from all
      cell lines examined, but the migration pattern differs between cell lines. The 5'
      flanking region of the dopamine beta-hydroxylase gene is also responsive to
      cyclic AMP and phorbol ester treatment of SHSY-5Y neuroblastoma cells. The
      simultaneous presence of both effectors results in synergistic increases in DBH1
      mRNA and reporter gene activity. The second messenger regulatory element was
      localized to the region containing the DB1 element, and reporter plasmids
      containing multiple copies of the DB1 element are responsive to treatment with
      inducers. The results of this study identify a cis-acting regulatory element
      which influences both cell type selectivity and second messenger responsiveness
      of the rat dopamine beta-hydroxylase gene.

PMID- 1382063
TI  - Regulation and light-harvesting complex II association of a Dunaliella protein
      homologous to early light-induced proteins in higher plants.
AB  - The unicellular green alga Dunaliella bardawil responds to high light, nutrient
      deprivation, and several other types of stress by massive accumulation of beta
      carotene. We have previously cloned a nuclear gene, cbr, that is co-induced with
      accelerated carotenogenesis. The predicted product of cbr is closely related to
      early light-induced proteins (Elips) of higher plants, and also shows resemblance
      to chlorophyll a/b-binding proteins. In the present study, the determination of
      the cbr transcription start site supported the previously proposed site of
      translation initiation. Antibodies raised against a synthetic oligopeptide
      matching the predicted sequence of Cbr recognized two polypeptides of apparently
      17 and 19 kDa that were induced in parallel to cbr transcript accumulation in
      highly illuminated or sulfate-starved D. bardawil cells. The antibodies also
      cross-reacted with an approximately 20-kDa polypeptide in sulfate-starved
      Dunaliella salina. In both D. bardawil and D. salina, Cbr was found exclusively
      in the thylakoid membranes. After mild solubilization, Cbr co-fractionated with
      light-harvesting complex II (LHCII) in sucrose gradient centrifugation and gel
      electrophoresis and was specifically associated with a minor LHCII complex. An
      occasionally observed, faster mobility Cbr form, free of LHCII, was probably
      released from the larger complex. These results support the conclusion that Cbr
      belongs to a class of stress-induced proteins transiently associated with
      antennae complexes.

PMID- 1382064
TI  - Cloning and characterization of the 5'-flanking region of the human topoisomerase
      II alpha gene.
AB  - Topoisomerases are essential enzymes for DNA metabolism in prokaryotes and
      eukaryotes. In human cells, DNA topoisomerase II enzyme activity can be modulated
      by both viral transformation and changes in proliferation status. To identify
      elements important for regulation of topoisomerase II alpha gene expression,
      genomic DNA clones covering the 5'-end of the gene were isolated. The intron/exon
      structure of a 2.5-kilobase region encompassing the translation start site was
      determined. Transcription was found to initiate at multiple sites clustered
      around 90 base pairs 5' to the ATG initiation codon. Transient expression of
      chimeric topoisomerase II-reporter gene constructs in HeLa cells revealed that
      the 5'-flanking region exhibited promoter activity. The region -90 to -1 upstream
      of the major transcription start site was shown by deletion analysis to include a
      promoter. This minimal promoter lacks a TATA box, is moderately GC-rich, and
      contains a high frequency of CpG dinucleotides; characteristic of a
      "housekeeping" gene promoter. Maximal promoter activity was observed using a
      fragment extending to position -562. Putative regulatory elements are contained
      within and immediately upstream of the minimal promoter region. The regulatory
      region of the topoisomerase II alpha gene identified here is similar in basic
      structure to those of the human thymidine kinase and DNA polymerase alpha genes,
      which are also controlled by proliferation-specific factors.

PMID- 1382065
TI  - Bombesin, vasopressin, and endothelin stimulation of tyrosine phosphorylation in
      Swiss 3T3 cells. Identification of a novel tyrosine kinase as a major substrate.
AB  - Neuropeptide-stimulated tyrosine phosphorylation of specific components in Swiss
      3T3 cells was investigated using monoclonal antibodies directed against the src
      transformation-associated substrates p125 focal adhesion kinase (FAK), a novel
      type of cytosolic tyrosine kinase, and p130. Treatment of Swiss 3T3 cells with
      the mitogenic peptides bombesin, vasopressin, and endothelin caused a striking
      increase in the tyrosine phosphorylation of p125FAK, as judged either by anti
      phosphotyrosine (anti-Tyr(P)) Western blots of anti-p125FAK immunoprecipitates,
      or by anti-p125FAK immunoblots of anti-Tyr(P) immunoprecipitates. Bombesin
      stimulated tyrosine phosphorylation of p125FAK was detectable within seconds and
      concentration-dependent (half-maximum effect of 0.3 nM). Neuropeptides also
      stimulated the tyrosine phosphorylation of a second component of M(r) 130,000,
      previously identified as the major p130 phosphotyrosyl protein in src-transformed
      cells. Bombesin stimulated p130 tyrosine phosphorylation with kinetics and
      concentration dependence similar to those observed for p125FAK. This is the first
      report to identify substrates for neuropeptide-stimulated tyrosine
      phosphorylation; the finding that one of these substrates is a tyrosine kinase
      suggests the existence of a novel signal transduction pathway in the action of
      mitogenic neuropeptides.

PMID- 1382066
TI  - Selective suppression of growth factor-induced cell cycle gene expression by
      Na+/H+ antiport inhibitors.
AB  - Activation of Na+/H+ exchange activity is a ubiquitous response to growth factors
      and has been implicated in the mitogenic response. Little is known of how the
      antiport influences events in the nucleus which ultimately control the cell
      cycle. Using potent Na+/H+ exchange inhibitors we show for normal mouse bone
      marrow-derived macrophages that this activity is required for the colony
      stimulating factor-1-induced gene expression of the M1 and M2 subunits of
      ribonucleotide reductase, an enzyme critical for DNA synthesis. Suppression of M1
      and M2 mRNA levels occurred when the inhibitors were added up to 8 h after the
      growth factor, mirroring their ability to prevent entry into S phase at similar
      times. Antiport activity was not required for the induction of other genes
      associated with cell cycle progression including proliferating cell nuclear
      antigen and the G1 cyclin, CYL1. These results highlight the differential
      expression of various cell cycle-associated genes and demonstrates that non
      coordinate regulation of CYL1 cyclin and DNA synthesis gene expression can occur.
      The selective dependence of ribonucleotide reductase subunit gene expression on
      Na+/H+ exchange activity may provide a biochemical basis for the requirement of
      persistent antiporter activity during G1 for subsequent entry into S phase.

PMID- 1382067
TI  - Location of the cytoplasmic epitope for a K(+)-competitive antibody of the
      (H+,K+)-ATPase.
AB  - The monoclonal antibody (mAb) 95-111 binds the alpha subunit of (H+,K+)-ATPase
      and inhibits the K(+)-ATPase activity. To map the epitope, all of the partial
      sequences of the alpha subunit were expressed in Escherichia coli HB101 using
      rabbit alpha subunit cDNA restriction fragments ligated into PuEx vector.
      Bacterial recombinant lysates were separated by sodium dodecyl sulfate-gel
      electrophoresis, and the epitope was detected by Western blotting. The antibody
      site was mapped between Cys529 and Glu561. This is close to the Lys517 that binds
      fluorescein isothiocyanate (FITC) and is considered to be between M4 and M5 close
      to the ATP binding domain. However, the mAb inhibition of ATPase is not ATP
      competitive but is K(+)-competitive with a KI of 2 x 10(-9) M. The mAb also
      inhibits K+ quench of FITC fluorescence competitively with a KI of 8 x 10(-9) M.
      The K+ activation of ATPase activity and quench of FITC fluorescence are
      dependent on K+ binding to an E2 form of the enzyme from the extracytoplasmic
      surface. The mAb epitope is cytoplasmic since the K(+)-ATPase activity of ion
      tight gastric vesicles is inhibited. The 125I-mAb 95-111 binds to a single class
      of sites with an apparent KD of 2.3 +/- 0.8 x 10(-9) M and K+ does not displace
      bound mAb. Hence, antibody binding to a cytoplasmic Cys529-Glu561 epitope
      allosterically competes with K(+)-dependent reactions at extracytoplasmic sites.

PMID- 1382068
TI  - On the mechanism by which bupivacaine conducts protons across the membranes of
      mitochondria and liposomes.
AB  - Bupivacaine and etidocaine possess the remarkable property of stimulating
      mitochondrial respiration to levels comparable with those observed with classical
      anionic protonophores (Dabadie, P., Bendriss, P., Erny, P., and Mazat, J.P.
      (1987) FEBS Lett. 226, 77-82). We show that these amphiphilic amines conduct
      protons across the membranes of mitochondria and liposomes and stimulate
      respiration by a true protonophoretic mechanism. The kinetics of drug-induced H+
      flux exhibited integer Hill coefficients that were greater than two under all
      conditions, suggesting that multimers are required for H+ transport. When the
      energy barrier for ion transport was lowered in mitochondria, by increasing the
      membrane potential, or in liposomes, by adding phloretin, the Hill coefficients
      decreased to lower integer numbers. Protonophoretic activity depended exclusively
      on medium concentration of free base, leading us to conclude that bupivacaine and
      etidocaine conduct protons as associated, intramembrane multimers of the free
      base. Bupivacaine-induced H+ leak was ohmic rather than nonohmic, as would be
      expected of a mobile charged carrier. This kinetic behavior seems improbable for
      a multimeric mobile carrier mechanism and suggests a channel mechanism, in which
      ohmicity results from splitting of the energy barrier by energy wells along the
      transport pathway (Garlid, K. D., Beavis, A. D., and Ratkje, S. K. (1989)
      Biochim. Biophys. Acta 976, 109-120). We hypothesize that bupivacaine and
      etidocaine act by a novel "flickering channel" mechanism, in which transient
      linear complexes of free base molecules provide weak binding sites (energy wells)
      for protons within lipid bilayer membranes.

PMID- 1382069
TI  - Labile proteins play a dual role in the control of endothelial leukocyte adhesion
      molecule-1 (ELAM-1) gene regulation.
AB  - Endothelial leukocyte adhesion molecule-1 (ELAM-1) is a membrane protein
      exclusively expressed on endothelial cells, where it plays a key role in the
      inflammatory response by adhering to a subset of leukocytes. The expression of
      the ELAM-1 gene is very tightly regulated. ELAM-1 is undetectable in uninduced
      cells, and it is transiently expressed following cytokine induction. Treatment of
      resting endothelial cells with three different protein synthesis inhibitors,
      cycloheximide (CHX), anisomycin, and emetine, caused an increase in the steady
      state level of ELAM-1 mRNA above that observed with IL (interleukin)-1 alone.
      Furthermore, ELAM-1 mRNA was found in the presence of all three protein synthesis
      inhibitors without IL-1 treatment. Analysis of the mRNA half-life indicated that
      the protein synthesis inhibitors act, in part, by stabilizing ELAM-1 mRNA. In
      addition, protein synthesis inhibitors potentiate the effect of IL-1 beta at the
      level of transcription initiation as shown by nuclear run-on experiments. The NF
      kappa B-like binding activity to the ELAM-1 promoter sequence induced by IL-1
      beta is augmented by inhibitors of protein synthesis. The NF kappa B binding
      sequence was found to be necessary and sufficient for superinduction of the ELAM
      1 gene by CHX. These results show that regulation at the level of protein
      synthesis is implicated in the overall regulation of ELAM-1 gene expression.
      Mechanisms which could explain these effects are discussed.

PMID- 1382070
TI  - Identification of the two major epidermal growth factor-induced tyrosine
      phosphorylation sites in the microvillar core protein ezrin.
AB  - In response to epidermal growth factor (EGF) the microvillar core protein ezrin
      is phosphorylated transiently to a high level on tyrosine residues in human
      epidermoid carcinoma A431 cells. Here we report the identification of the
      tyrosine phosphorylation sites in ezrin using bacterially expressed protein as a
      substrate for in vitro phosphorylation with the EGF receptor. The two major
      phosphotyrosine-containing peptides observed in vivo were also phosphorylated in
      vitro. By secondary digestions and site-directed mutagenesis tyrosines 145 and
      353 were identified as the sites of phosphorylation. One of the sites, Tyr145,
      lies in the N-terminal region of homology that is common to the band 4.1-talin
      ezrin protein family. This tyrosine residue and its vicinal amino acids are
      conserved throughout the family members, including radixin, moesin, and the two
      phosphotyrosine phosphatases, PTP H1 and PTP MEG, but not in band 4.1 or talin.
      Tyr353 is localized within the alpha-helical domain of ezrin and comparison of
      the protein sequences reveals that this site is unique to ezrin.

PMID- 1382071
TI  - Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) gene
      transcription and alternative RNA splicing in a model of developing intestinal
      epithelium.
AB  - Transcriptional and post-transcriptional regulation of CFTR (cystic fibrosis
      transmembrane conductance regulator) gene expression was studied in HT29 cells.
      It is known that the abundance of CFTR mRNA increases during differentiation of
      pluripotent HT29-18 cells and is maintained at high levels in the stably
      differentiated HT29-18-C1 subclone. Nuclear run-on assays suggest that increased
      transcription of the CFTR gene explains the increased abundance of total CFTR
      mRNA in differentiated HT29 cells. The increased transcription cannot be ascribed
      to cell cycle-dependent expression of the CFTR gene or to changes in CFTR gene
      copy number between subcloned cells. Similar to native tissue cells,
      differentiated HT29 cells contain low copy numbers of CFTR transcripts (1
      5/cell), and a portion of the CFTR transcripts are alternatively spliced to
      remove exon 9 (and make 9-mRNA). During differentiation of HT29-18 cells, the
      absolute amount of full-length CFTR mRNA increases 8-fold, whereas the amount of
      9- mRNA increases 18-fold. The fraction of 9- mRNA in the CFTR mRNA pool is
      increased in differentiated HT29 cells. The results show that gene transcription
      regulates the abundance of CFTR transcripts and that regulatory control of
      alternative RNA splicing may also be a cellular mechanism to modulate CFTR
      function.

PMID- 1382072
TI  - Interaction of tRNALys with the p66/p66 form of HIV-1 reverse transcriptase
      stimulates DNA polymerase and ribonuclease H activities.
AB  - The precursor homodimeric p66/p66 form of human immunodeficiency virus type-1
      reverse transcriptase (HIV-1 RT) possesses the DNA polymerase and RNase H
      activities involved in the synthesis of the double-stranded provirus DNA. Reverse
      transcription is initiated from tRNALys in the case of HIV-1. The present study
      confirmed that interactions between HIV-1 RT and tRNALys induce protein
      conformational changes and demonstrated that these interactions stimulate the
      enzymatic activities associated with the p66 subunit. Thus, the p66/p66 form of
      the enzyme is strongly stimulated in both DNA polymerase and RNase H activities.
      Preincubation of the enzyme with tRNA is an obligatory step to obtain the
      stimulatory effect. The affinity of template, primer, or substrate for RT p66/p66
      did not change when the enzyme was preincubated with tRNALys at stimulatory
      concentrations; the interaction of tRNA with p66/p66 has an effect only on the
      maximal rate of polymerization. It is further shown that the RNase H domain of RT
      is much more accessible to protease attack than the DNA polymerase active site.

PMID- 1382073
TI  - Interaction of secreted insulin-like growth factor-I (IGF-I) with cell surface
      receptors is the dominant mechanism of IGF-I's autocrine actions.
AB  - In a prior report we presented evidence that insulin-like growth factor-I (IGF-I)
      can act in an autocrine fashion by demonstrating that FRTL-5 cells transfected
      with hIGF-IA fusion genes express and secrete biologically active IGF-I that
      renders the stimulation of DNA synthesis in FRTL-5 cells independent of their
      requirement for exogenous IGFs or insulin. To determine if IGF-I's autocrine
      actions require secretion or can be mediated by interactions with intracellular
      receptors, we have created a new line of FRTL-5 cells that express a mutant IGF
      IA precursor containing the endoplasmic reticulum retention amino acid sequence,
      Lys-Asp-Glu-Leu (KDEL), at its carboxyl terminus. The mutant IGF-IA/KDEL
      precursor expressed by stably transfected FRTL-5 cells was shown to be retained
      intracellularly and to have biological activity comparable with mature IGF-I, as
      judged by the activity of partially purified IGF-IA/KDEL in wild type FRTL-5
      cells. Expression of IGF-IA/KDEL in FRTL-5 cells, however, neither augmented TSH
      stimulated DNA synthesis nor stimulated IGF-binding protein-5 expression, as does
      IGF-IA expression in transfected FRTL-5 cells and the addition of exogenous IGF-I
      to wild type FRTL-5 cells. IGF-IA/KDEL expression, however, desensitized FRTL-5
      cells to the actions of exogenous IGF-I despite having only minimal effects on
      cell surface type I receptor number, suggesting that intracellular IGF-I is
      capable of significant biological actions. The failure of IGF-IA/KDEL to
      replicate the actions of secreted IGF-I, taken together with the findings that a
      monoclonal antibody against IGF-I blocked IGF-I's actions in IGF-I-secreting
      transfected FRTL-5 cells, provides evidence that IGF-I secretion and interaction
      with cell surface type I IGF receptors is the dominant mechanism of IGF-I's
      autocrine actions.

PMID- 1382074
TI  - Role of CAAT-enhancer binding protein isoforms in the cytokine regulation of
      acute-phase plasma protein genes.
AB  - Rat hepatic cells respond to interleukin (IL) -1, IL-6, and dexamethasone
      treatment by increasing the transcription rate of acute-phase plasma protein
      genes. The same conditions lead to changes in the expression of CAAT-enhancer
      binding protein (C/EBP) isoforms which are specific to the hepatic cell line. To
      identify the relationship between C/EBP isoforms and acute-phase protein gene
      activation, the hormone-specific expression of C/EBP alpha, beta, and delta was
      determined in H-35 and HTC cells and was compared to acute-phase liver. C/EBP
      beta was found to be the principal isoform in hepatoma cells and to be strongly
      stimulated by cytokines and dexamethasone in H-35 cells. Transactivating
      functions were observed for all three C/EBP isoforms by cotransfection of CAT
      gene reporter constructs containing cytokine and glucocorticoid response elements
      of acute-phase protein genes and expression plasmids for mouse C/EBP alpha, beta,
      and delta into rat and human hepatoma cells. The degree of C/EBP-mediated
      transactivation was, however, extremely variable among the different regulatory
      elements. Transcription run-on reactions with nuclei from transiently transfected
      H-35 cells indicated that cotransfected C/EBP beta increases basal expression of
      reporter gene constructs as well as the dexamethasone-mediated stimulation of
      constructs containing the glucocorticoid response elements of the rat alpha 1
      acid glycoprotein gene, but did not accelerate or enhance hormone-dependent
      transcription activation of reporter gene plasmids containing the IL-6 regulatory
      element of the beta-fibrinogen gene. Activation of the reporter gene constructs
      appeared to be temporally and quantitatively correlated with the amount of
      nuclear C/EBP as determined by two-dimensional Western and Southwestern blot
      analyses.

PMID- 1382075
TI  - Physical and biological properties of a new synthetic amino acid copolymer used
      as wound dressing.
AB  - A new synthetic amino acid copolymer has been evaluated as wound covering. It is
      permeable to water vapor in the region of 4.1 kg/m2/24 h, it does not allow
      microbial proliferation after in vitro inoculation, it is impermeable to
      bacteria, and is stable and flexible. In vivo experiments were designed to
      provide qualitative and quantitative evaluation on its possible use as a skin
      substitute in full-thickness skin excision in the guinea pig. Two excisions,
      approximately 12-14 cm2 were performed on each side of the spine, leaving the
      panniculus carnosus. One site was treated with the membrane, the other with
      gauze. Each animal served as its own control. Photographs with a fixed focal
      length camera were taken in identical conditions for all wounds immediately and
      7, 14, and 21 days after excision. They were analyzed by planimetry. Histological
      studies were performed at 7, 14, and 21 days. The rate of healing between 0 and
      21 days of the wounds treated with the copolymer membrane was significantly
      accelerated in comparison with wounds covered with a dry dressing (p less than
      0.05). This increased epithelialization rate was confirmed by histology, which
      also suggested a reduction of the inflammatory response of the wound. In vivo
      biodegradation studies were also performed by subcutaneous implantation in the
      rat followed at 15, 30, 60, and 90 days by histology and physicochemical
      analyses. The results demonstrate that the membrane is not biodegradable.

PMID- 1382076
TI  - Neuronal cell adhesion molecule contactin/F11 binds to tenascin via its
      immunoglobulin-like domains.
AB  - Adhesive interactions between neurons and extracellular matrix (ECM) play a key
      role in neuronal pattern formation. The prominent role played by the
      extracellular matrix protein tenascin/cytotactin in the development of the
      nervous system, tied to its abundance, led us to speculate that brain may contain
      yet unidentified tenascin receptors. Here we show that the neuronal cell adhesion
      molecule contactin/F11, a member of the immunoglobulin(Ig)-superfamily, is a cell
      surface ligand for tenascin in the nervous system. Through affinity
      chromatography of membrane glycoproteins from chick brain on tenascin-Sepharose,
      we isolated a major cell surface ligand of 135 kD which we identified as
      contactin/F11 by NH2-terminal sequencing. The binding specificity between
      contactin/F11 and tenascin was demonstrated in solid-phase assays. Binding of
      immunopurified 125I-labeled contactin/F11 to immobilized tenascin is completely
      inhibited by the addition of soluble tenascin or contactin/F11, but not by
      fibronectin. When the fractionated isoforms of tenascin were used as substrates,
      contactin/F11 bound preferentially to the 190-kD isoform. This isoform differs in
      having no alternatively spliced fibronectin type III domains. Our results imply
      that the introduction of these additional domains in some way disrupts the
      contactin/F11 binding site on tenascin. To localize the binding site on
      contactin/F11, proteolytic fragments were generated and characterized by NH2
      terminal sequencing. The smallest contactin/F11 fragment which binds tenascin is
      45 kD and also begins with the contactin/F11 NH2-terminal sequence. This implies
      that contactin/F11 binds to tenascin through a site within the first three Ig
      domains.

PMID- 1382077
TI  - Identification of an E-selectin region critical for carbohydrate recognition and
      cell adhesion.
AB  - E-selectin elicits cell adhesion by binding to the cell surface carbohydrate,
      sialyl Lewis X (sLe(x)). We evaluated the effects of mutations in the E-selectin
      lectin domain on the binding of a panel of anti-E-selectin mAbs and on the
      recognition of immobilized sLe(x) glycolipid. Functional residues were then
      superimposed onto a three-dimensional model of the E-selectin lectin domain. This
      analysis demonstrated that the epitopes recognized by blocking mAbs map to a
      patch near the antiparallel beta sheet derived from the NH2 and COOH termini of
      the lectin domain and two adjacent loops. Mutations that affect sLe(x) binding
      map to this same region. These results thus define a small region of the E
      selectin lectin domain that is critical for carbohydrate recognition.

PMID- 1382080
TI  - Visualization of DNA within mitochondria by osmium-ammine staining of mouse
      duodenal crypt cells.
AB  - Previous investigators have examined mitochondrial DNA (mtDNA) in the electron
      microscope (EM) after extraction from mitochondria and rotary shadowing. We have
      observed mtDNA in situ by the osmiumammine procedure for specific staining of DNA
      in the EM. The procedure was modified to improve the regularity of the staining
      and then applied to the rapidly dividing cells present in mouse duodenal crypts.
      In the stained sections of these cells, 25% of the mitochondria exhibited
      discrete reactive filaments. The filaments, whether observed directly or in
      stereopairs, appeared either irregular or arranged into distinct patterns, some
      of which were similar to those previously described after rotary shadowing of
      duplicating mtDNA: namely, simple and double circular figures, displacement loops
      and supercoiled forms. The filaments could be traced in serial sections of the
      same mitochondria and, therefore, were not artifacts. Moreover, their
      disappearance after DNase digestion demonstrated that they were composed of DNA.
      It is concluded that mtDNA can be visualized by the modified osmium-ammine
      technique and may show patterns that can be interpreted as phases in its
      replication.

PMID- 1382078
TI  - Soluble L-selectin is present in human plasma at high levels and retains
      functional activity.
AB  - L-selectin expressed by granulocytes, lymphocytes, and monocytes is responsible
      for initial leukocyte attachment to inflamed endothelium and high endothelial
      venules of peripheral lymph nodes. After leukocyte activation in vitro, L
      selectin is rapidly shed from the cell surface. In this study, shed L-selectin
      (sL-selectin) from both lymphocytes and neutrophils was demonstrated to be
      present in high levels in human plasma by Western blot analysis and using a
      quantitative ELISA. In serum from normal human blood donors, a mean sL-selectin
      level of 1.6 +/- 0.8 micrograms/ml (n = 63) was found by ELISA. In addition,
      semipurified sL-selectin from plasma inhibited L-selectin-specific attachment of
      lymphocytes to cytokine-activated endothelium in a dose-dependent manner. L
      selectin-dependent leukocyte attachment was completely inhibited at sL-selectin
      concentrations of 8-15 micrograms/ml, while physiological concentrations of sL
      selectin caused a small but consistent inhibition of lymphocyte attachment. sL
      selectin in plasma also inhibited anti-L-selectin mAb (2-5 micrograms/ml) binding
      to the surface of leukocytes. Interestingly, one epitope present within the EGF
      like domain of L-selectin was lost in sL-selectin, suggesting a conformational
      change in the structure of the receptor after shedding. The presence of serum sL
      selectin with functional activity indicates a potential role for sL-selectin in
      the regulation of leukocyte attachment to endothelium.

PMID- 1382079
TI  - Second messengers regulate endosomal acidification in Swiss 3T3 fibroblasts.
AB  - Acidification of the endosomal pathway is important for ligand and receptor
      sorting, toxin activation, and protein degradation by lysosomal acid hydrolases.
      Fluorescent probes and imaging methods were developed to measure pH to better
      than 0.2 U accuracy in individual endocytic vesicles in Swiss 3T3 fibroblasts.
      Endosomes were pulse labeled with transferrin (Tf), alpha 2-macroglobulin (alpha
      2M), or dextran, each conjugated with tetramethylrhodamine and carboxyfluorescein
      (for pH 5-8) or dichlorocarboxyfluorescein (for pH 4-6); pH in individual labeled
      vesicles was measured by ratio imaging using a cooled CCD camera and novel image
      analysis software. Tf-labeled endosomes acidified to pH 6.2 +/- 0.1 with a t1/2
      of 4 min at 37 degrees C, and remained small and near the cell periphery. Dextran
      and alpha 2M-labeled endosomes acidified to pH 4.7 +/- 0.2, becoming larger and
      moving toward the nucleus over 30 min; approximately 15% of alpha 2M-labeled
      endosomes were strongly acidic (pH less than 5.5) at only 1 min after labeling.
      Replacement of external Cl by NO3 or isethionate strongly and reversibly
      inhibited acidification. Addition of ouabain (1 mM) at the time of labeling
      strongly enhanced acidification in the first 5 min; Tf-labeled endosomes
      acidified to pH 5.3 without a change in morphology. Activation of phospholipase C
      by vasopressin (50 nM) enhanced acidification of early endosomes; activation of
      protein kinase C by PMA (100 nM) enhanced acidification strongly, whereas
      elevation of intracellular Ca by A23187 (1 microM) had no effect on
      acidification. Activation of protein kinase A by CPT-cAMP (0.5 mM) or forskolin
      (50 microM) inhibited acidification. Lysosomal pH was not affected by ouabain or
      the protein kinase activators. These results establish a methodology for
      quantitative measurement of pH in individual endocytic vesicles, and demonstrate
      that acidification of endosomes labeled with Tf and alpha 2M (receptor-mediated
      endocytosis) and dextran (fluid-phase endocytosis) is sensitive to intracellular
      anion composition, Na/K pump inhibition, and multiple intracellular second
      messengers.

PMID- 1382081
TI  - A monoclonal antibody, raised against mammalian centrosomes and screened by
      recognition of plant microtubule organizing centers, identifies a pericentriolar
      component in different cell types.
AB  - We have used monoclonal antibodies raised against isolated native calf thymus
      centrosomes to probe the structure and composition of the pericentriolar
      material. To distinguish prospective antibodies as specific to conserved elements
      of this material, we screened clones by their identification of microtubule
      organizing centers (MTOCs) in different animal and plant cells. Among the clonal
      antibodies that reacted with MTOCs in both plant and mammalian cells, we describe
      one (mAb 6C6) that was found to immunostain centrosomes in a variety of bovine
      and human cells. In cycling cells this signal persisted through the entire cell
      cycle. Microscopy showed that the mAb 6C6 antigen was a component of the
      pericentriolar material and this was confirmed by biochemical analysis of
      centrosomes. Using immunoblot analysis of protein fractions derived from purified
      components of centrosomes, we have characterized the mAb 6C6 antigen as a 180 kDa
      polypeptide. We conclude that we have identified a protein component permanently
      associated with the pericentriolar material. Surprisingly, monoclonal antibody
      6C6 also stained other mitotic organelles in mammalian cells, in a cell-cycle
      dependent manner. During prometaphase and metaphase the antibody stained both
      centrosomes and kinetochores. At the onset of anaphase the kinetochore-specific
      staining dissociated from chromosomes and was subsequently redistributed onto a
      newly characterized organelle, the telophase disc while the centrosomal stain
      remained intact. It is not known if the 180 kDa centrosomal protein itself
      redistributes during mitosis, or if the pattern observed represents other
      antigens with shared epitopes. The pericentriolar material is thought to be
      composed of conserved elements, which appeared very early during the evolution of
      eukaryotes. Our results strongly suggest that mAb 6C6 identifies one of these
      elements.

PMID- 1382082
TI  - Endothelium-dependent dilator response to substance P in patients with coronary
      spastic angina.
AB  - OBJECTIVE: This study was designed to examine whether patients with coronary
      spastic angina have an impaired coronary artery dilator response to substance P,
      an endothelium-dependent vasodilator. BACKGROUND: Impairment of the endothelium
      dependent vasodilator response has been suggested to be involved in the
      pathogenesis of coronary spasm. METHODS: In 11 patients with coronary spastic
      angina and 11 control patients, substance P was infused into the coronary artery
      at 20 pmol/min for 5 min. Incremental doses of acetylcholine were then injected
      into the coronary artery. The effects of these drugs and nitroglycerin on the
      coronary artery diameter were quantitatively analyzed. RESULTS: Heart rate,
      systolic blood pressure and rate-pressure product did not change after substance
      P infusion. In 12 coronary arteries of the patients with coronary spastic angina,
      spasm was induced with acetylcholine. At the site of coronary spasm documented,
      the lumen diameter, which was 1.6 +/- 0.5 mm at baseline, increased to 2.1 +/-
      0.7 mm after substance P infusion (p less than 0.01). It decreased to 0.2 +/- 0.3
      mm during acetylcholine-induced spasm (p less than 0.001) and increased to 2.3 +/
      0.8 mm after nitroglycerin administration (p less than 0.001 vs. baseline and p
      = NS vs. after substance P infusion). Of the 12 arteries with spasm, 5 were
      angiographically normal and the other 7 were minimally or moderately
      atherosclerotic: the diameter change after substance P was +28 +/- 20% and +30 +/
      22%, respectively (p = NS). In control patients, the diameter of the middle
      portion of the left anterior descending artery, which was 2.0 +/- 0.4 mm at
      baseline, increased to 2.5 +/- 0.4 mm after substance P infusion (p less than
      0.001). The diameter changes after substance P infusion were not different
      between the patients with coronary spastic angina and control patients.
      CONCLUSIONS: Substance P dilated the artery with spasm of the patients with
      coronary spastic angina to a degree similar to that in control patients,
      indicating the preserved endothelium-dependent dilator response at the site of
      coronary spasm by way of substance P receptor.

PMID- 1382083
TI  - Cells and mediators involved in immunoglobulin synthesis by human circulating
      mononuclear cells. IV. B cells synthesize but do not secrete immunoglobulins
      because of a defect in the non-T non-B (null) cells.
AB  - Null cells (non-T and non-B lymphocytes) have previously been demonstrated to be
      obligatory participants for immunoglobulin synthesis and secretion by normal B
      cells in culture. Normal null cells have been demonstrated to secrete a factor,
      human immunoglobulin synthesis/secretion-facilitating factor (HISFF), which can
      replace the null cells in the culture. In this investigation, the B cells of an 8
      month-old male infant and a 46-year-old male adult who presented with a humoral
      (antibody) immunodeficiency syndrome synthesized immunoglobulin but did not
      secrete immunoglobulin after culture with pokeweed mitogen and autologous T
      cells, monocytes, and null cells. In contrast, the patients' B cells synthesized
      and secreted immunoglobulin after the addition of allogeneic normal null cells or
      HISFF to the cultures. The same results were obtained with the cells of the
      infant and the adult patient tested at monthly intervals for 4 months. The
      results demonstrate that the patients' T cells, B cells, and monocytes functioned
      normally and that only the patients' null cells were defective. These findings
      provide an explanation for the absence of immunoglobulin in the circulation of
      "non(immunoglobulin)secretors," although they possess normal numbers of
      circulating immunoglobulin-synthesizing B cells. The defect is in the null cell
      and not in the B cell and consists of the inability of the null cell to secrete
      HISFF that facilitates the synthesis and secretion of immunoglobulin by the B
      cell.

PMID- 1382084
TI  - Prospects for ancillary treatment of sinusitis in the 1990s.
AB  - The basis for ancillary therapy of sinusitis derives from anecdotal accounts and
      personal beliefs rather than definitive data. The recent appreciation that
      noninfectious inflammatory causes predispose to infectious sinusitis has
      stimulated renewed interest in developing and documenting efficacious ancillary
      therapies that could supplement or abrogate antibiotic use. Ancillary therapies
      of sinusitis could be directed toward (1) preventing viral upper respiratory
      tract infections (immunizations, virucidal-impregnated tissues, and proper hand
      washing techniques); (2) blocking rhinoviral replication and suppressing mediator
      release with supraphysiologic nasal hyperthermia, although contradictory studies
      exist with regard to efficacy; (3) promoting sinus and nasal ventilation with
      both topical and oral alpha-agonists and exercise; (4) improving mucociliary
      clearance by reducing mucus viscosity and elasticity with saline solution
      irrigation, mucoregulators (N-acetylcysteine, S-carboxymethylcysteine, and
      iodinated glycerol), and ciliary stimulants (adenosine triphosphate); and (5)
      suppressing/modulating cellular inflammation (eosinophilic, basophilic, and
      neutrophilic) with topical nasal corticosteroid sprays and mediator antagonists.
      Recommendations are forwarded for future investigations of promising
      nonantibiotic ancillary therapies of chronic sinusitis.

PMID- 1382085
TI  - Sinusitis and asthma: an animal model.
AB  - We have developed an animal model in which nonspecific lower airways
      hyperresponsiveness to inhaled histamine was elicited in rabbits after complement
      induced maxillary sinusitis. The most likely mechanism to explain this occurrence
      is the direct passage ("postnasal drip") of inflammatory mediators from the upper
      to the lower respiratory tract. The contribution of other potential mechanisms,
      such as the blood-borne delivery of inflammatory mediators, nasobronchial
      reflexes, and passage of cells with the induction of a secondary inflammatory
      process, could not be demonstrated. Rather, the most likely explanation for the
      current finding is the passage of mediators elaborated from activated
      inflammatory cells into the lower airways. Whether these findings explain the
      common clinical association of upper airways disease to lower airways dysfunction
      in sinusitis and asthma remains to be determined. These results suggest that even
      small numbers of granulocytes, when activated, can exert significant effect on
      lower airways function. It is perhaps appropriate to speculate at this point
      about the anecdotal but dramatic improvement in the asthma of patients with
      sinusitis who undergo surgery. The current results cause us to suggest that this
      success is due to the removal of the source of inflammatory products that drip
      into the lung. More important, these current results may have an important
      implication in the diagnosis of asthma. Finally, there is the clear conclusion
      that airways dysfunction can be caused by a mechanism that is associated with
      inflammation but without evidence of cell migration into the airways.

PMID- 1382086
TI  - Bioavailability and biological activity of wheat-bound chlorpyrifos-methyl
      residues in rats.
AB  - Wheat grain was treated with 14C-chlorpyrifos-methyl to generate bound residues
      for determining their bioavailability to rats. In a parallel experiment, bound
      residues were prepared with non-labelled chlorpyrifos-methyl to determine
      possible adverse effects in rats fed the grain-bound residue for 28 and 90 days.
      Two dose levels of 10 and 50 ppm were initially used on the grain. The 10 ppm led
      to the formation of 25.1% bound residues (2.51 ppm) after 6 months as determined
      by radiomeasurement. The higher dose was assumed to form 12.55 ppm bound
      residues. When 14C-bound residues were fed to male rats for 24 hours, the animals
      eliminated 75% of the radioactivity in urine, 7% in expired air and 8% in faeces
      after 3 days, indicating that the bound residues were highly bioavailable. A
      further "bioavailable" amount (4%) was found in selected organs.

PMID- 1382087
TI  - Mapping of neural nitric oxide synthase in the rat suggests frequent co
      localization with NADPH diaphorase but not with soluble guanylyl cyclase, and
      novel paraneural functions for nitrinergic signal transduction.
AB  - Nitric oxide synthases (NOS Types I-III) generate nitric oxide (NO), which in
      turn activates soluble guanylyl cyclase (GC-S). The distribution of this NO
      mediated (nitrinergic) signal transduction pathway in the body is unclear. A
      polyclonal monospecific antibody to rat cerebellum NOS-I and a monoclonal
      antibody to rat lung GC-S were employed to localize the protein components of
      this pathway in different rat organs and tissues. We confirmed the localization
      of NOS-I in neurons of the central and peripheral nervous system, where NO may
      regulate cerebral blood flow and mediate long-term potentiation. GC-S was located
      in NOS-negative neurons, indicating that NO acts as an intercellular signal
      molecule or neurotransmitter. However, NOS-I was not confined to neurons but was
      widely distributed over several non-neural cell types and tissues. These included
      glia cells, macula densa of kidney, epithelial cells of lung, uterus, and
      stomach, and islets of Langerhans. Our findings suggest that NOS-I is the most
      widely distributed isoform of NOS and, in addition to its neural functions,
      regulates secretion and non-vascular smooth muscle function. With the exception
      of bone tissue, NADPH-diaphorase (NADPH-d) activity was generally co-localized
      with NOS-I immunoreactivity in both neural and non-neural cells, and is a
      suitable histochemical marker for NOS-I but not a selective neuronal marker.

PMID- 1382088
TI  - Renal tubule gp330 is a calcium binding receptor for endocytic uptake of protein.
AB  - gp330, a large glycoprotein located in renal proximal tubules, has sequence
      similarities with the low-density lipoprotein receptor and the alpha 2
      macroglobulin receptor/low-density lipoprotein receptor-related protein. The 40
      KD human alpha 2-macroglobulin receptor-associated protein is a newly discovered
      heparin binding protein homologous to a major rat Heymann nephritis factor and
      exhibiting high affinity binding to the alpha 2-macroglobulin receptor. The
      present study shows by ligand blotting, light and electron microscopic
      autoradiography, and cytochemistry that gp330 located in coated apical membrane
      regions of the rat proximal tubule strongly binds the 40 KD protein. Furthermore,
      45Ca2+ blotting experiments disclosed gp330 as a quantitatively important Ca2+
      binding protein in renal cortex. Binding of 125I-labeled 40 KD protein to
      electroblotted gp330 and to coated apical membrane regions in sections of renal
      proximal tubules was abolished by excess unlabeled 40 KD protein, heparin, and
      EDTA. The endocytic properties of gp330 were investigated by in vivo
      microperfusion of rat proximal tubules. After 6 min, 125I-labeled 40 KD protein
      was mainly found in endocytic vacuoles and later accumulated in lysosomes. These
      data demonstrate that gp330 is a Ca2+ binding receptor for endocytosis of protein
      and is functionally related to the alpha 2-macroglobulin receptor/low-density
      lipoprotein receptor-related protein. Furthermore, our results demonstrate the
      usefulness of semi-thin and ultra-thin cryosections in studies of ligand binding
      and subcellular localization of receptors with autoradiographic techniques.

PMID- 1382089
TI  - Mosaic lectin and enzyme staining patterns in rat skeletal muscle.
AB  - We compared the localizations of lectin binding and activity for myosin ATPase
      and succinic dehydrogenase in sections of the gracilis, soleus, and masseter
      muscles from 10- and 60-day-old rats. In the 60-day-old rats, incubation of the
      muscle sections with the lectins ConA, GS-II, HPA, and jacalin gave rise to a
      mosaic staining pattern, especially in the gracilis muscle, in which the same
      fibers were strongly stained for ConA, GS-II, and HPA, whereas the staining with
      jacalin in these fibers was weak, and vice versa. There was no correspondence in
      the staining patterns for the enzymes and the lectins. In the masseter muscle
      only GS-II gave rise to distinct differences in the staining intensity between
      muscle fibers. In 10-day-old rats all fibers in the muscles were moderately
      stained with ConA, HPA, and jacalin, whereas a chessboard staining pattern could
      be observed after incubation with GS-II. In an extract of hindleg muscle from 60
      day-old rats there was strong affinity for ConA and HPA and weak affinity for GS
      II and jacalin, as shown by dot-blotting. After electrophoresis and blotting to
      nitrocellulose membranes, three muscle protein bands with apparent molecular
      weights of 100,000, 90,000, and 43,000 showed affinity for ConA, HPA, and GS-II,
      whereas no bands were jacalin positive. The complex lectin staining pattern in
      skeletal muscle might be related to development, specialization, and function of
      the muscles.

PMID- 1382090
TI  - Cytoskeleton in neuroectodermally derived epithelial and muscle cells of the
      human iris and ciliary body.
AB  - The cytoskeleton of epithelial and muscle cells of the human iris and ciliary
      body was analyzed by immunohistochemistry in three morphologically normal
      formalin-fixed, paraffin-embedded eyes and in 34 eyes containing a uveal
      melanoma. Both layers of the iris epithelium reacted with monoclonal antibodies
      (MAb) V9 and Vim 3B4 to vimentin, whereas the ciliary epithelia additionally
      reacted with MAb CAM 5.2, CK5, KS-B17.2, and CY-90, recognizing cytokeratins 8
      and 18. The same cytokeratin MAb labeled the retinal pigment epithelium, which
      lacked vimentin. The muscle portion of the anterior iris epithelium, which forms
      the dilator muscle, as well as the sphincter and ciliary muscles, reacted with
      MAb DE-U-10 to desmin and 1A4 to alpha-smooth muscle actin. The dilator and
      ciliary muscles also reacted with V9 and Vim 3B4 to vimentin, and some dilator
      fibers were weakly immunopositive for cytokeratin 8 and 18 with CY-90 and CAM
      5.2. The antigenic profile of iris and ciliary epithelia infiltrated by melanoma
      cells remained unchanged. The intraocular epithelia, which are developmentally
      related but differ in function, and the intraocular muscles, which differ in
      origin but are functionally related, have distinct cytoskeletal profiles and may
      provide insights into the functional significance of intermediate filament
      expression.

PMID- 1382091
TI  - Detection of CD1 mRNA in Paneth cells of the mouse intestine by in situ
      hybridization.
AB  - Cluster of differentiation 1 (CD1) antigens are a family of non-MHC but Class I
      like molecules that have been identified in humans and rodents. Although their
      function(s) remains unknown, it has been proposed that CD1 may present antigens
      to specific subsets of peripheral T-cells. We now provide evidence in support of
      this hypothesis through the demonstration by in situ hybridization that Paneth
      cells of the mouse intestine express CD1 mRNA. These cells are thought to be
      involved in the immunological regulation of intestinal flora and could accomplish
      this task through interactions with intestinal intraepithelial lymphocytes. The
      expression and localization of CD1 mRNA was confirmed by both autoradiographic
      and non-isotopic techniques. The relevance of these results to CD1 function as
      well as to Paneth cell biology is discussed.

PMID- 1382092
TI  - Fast myosin light chain expression in chicken muscles studied by in situ
      hybridization.
AB  - We have studied the fiber type-specific expression of the fast myosin light chain
      isoforms LC 1f, LC 2f, and LC 3f in adult chicken muscles using in situ
      hybridization and two-dimensional gel electrophoresis. Type II (fast) fibers
      contain all three fast myosin light chain mRNAs; Types I and III (slow) fibers
      lack them. The myosin light chain patterns of two-dimensional gels from
      microdissected single fibers match their mRNA signals in the in situ
      hybridizations. The results confirm and extend previous studies on the fiber type
      specific distribution of myosin light chains in chicken muscles which used
      specific antibodies. The quantitative ratios between protein and mRNA content
      were not the same for all three fast myosin light chains, however. In bulk muscle
      samples, as well as in single fibers, there was proportionally less LC 3f
      accumulated for a given mRNA concentration than LC 1f or LC 2f. Moreover, the
      ratio between LC 3f mRNA and protein was different in samples from muscles,
      indicating that LC 3f is regulated somewhat differently than LC 1f and LC 2f. In
      contrast to other in situ hybridization studies on the fiber type-specific
      localization of muscle protein mRNAs, which reported the RNAs to be located
      preferentially at the periphery of the fibers, we found all three fast myosin
      light chain mRNAs quite evenly distributed within the fiber's cross-sections, and
      also in the few rare fibers which showed hybridization signals several-fold
      higher than their surrounding counterparts. This could indicate principal
      differences in the intracellular localization among the mRNAs coding for various
      myofibrillar protein families.

PMID- 1382093
TI  - The nature of large noncovalent complexes containing glycosyl
      phosphatidylinositol-anchored membrane glycoproteins and protein tyrosine
      kinases.
AB  - A significant fraction of human glycosyl-phosphatidylinositol-anchored Ag CD59,
      CD55, CD48, and CDw52 is present in several cell lines tested (HPB-ALL, Jurkat,
      HL-60, Raji) in very large noncovalent complexes relatively resistant to
      dissociation by detergents. These complexes also contain some (glyco)lipids, such
      as these bearing the CD15, CDw17, and CDw65 determinants, and several
      intracellular components including protein tyrosine kinases and probably several
      of their potential substrates. Preclearing of the detergent lysates with
      different antibodies indicated that all these components are present jointly in a
      common single type of complexes the size of which is around 100 nm (molecular
      mass in the range of at least tens of thousands kilodaltons) as determined by
      ultrafiltration and gel chromatography. These results indicate the existence of
      cell-surface domains, specifically enriched in the above listed components, that
      may play a critical role in the so far poorly understood phenomenon of cell
      activation mediated through many different glycosyl-phosphatidylinositol-anchored
      (glyco)proteins and glycolipids.

PMID- 1382094
TI  - Phenotypic and functional characterization of c-kit expression during intrathymic
      T cell development.
AB  - We have studied the expression and function of c-kit on subsets of mouse
      thymocytes. c-kit was primarily expressed on subpopulations of CD4-CD8-CD3-
      triple negative (TN) cells. The strongest c-kit expression was associated with
      subsets that represent the least mature TN cells, including CD44+CD25- TN, and a
      subpopulation of CD25+ TN. These cells were also Thy-1lo, H-2Khi TSA-1hi, HSAlo,
      B220-, Mac-1-, and Gr-1-. Additionally, the recently described pre-TN thymocyte
      population (CD4loCD3-CD8-) was also c-kit+. CD25+ TN thymocytes proliferated in
      the presence of IL-7 and stem cell factor (the ligand for c-kit), and this
      proliferation was completely inhibited in the presence of anti-c-kit.
      Furthermore, the addition of anti-c-kit to 2-deoxyguanosine-treated fetal thymic
      lobes undergoing reconstitution with fetal liver-derived precursor cells
      inhibited their T cell differentiation potential. These observations indicate an
      important role for c-kit/stem cell factor interactions during early thymocyte
      development.

PMID- 1382095
TI  - Self-reactive, T cell receptor-gamma delta+, lymphocytes from the intestinal
      epithelium of weanling mice.
AB  - Intraepithelial T lymphocytes (IEL) are dispersed throughout the intestinal
      epithelial lining but their role in cellular immune defense is unknown. Their
      location suggests that their highly activated state may be due to constant
      exposure to bacterial Ag. To study IEL specificity and function we have prepared
      a panel of IEL-T cell hybridomas from both adult and weanling C57B1/6 mice. Many
      of these expressed TCR-gamma delta, a cell type rare in peripheral lymph nodes
      and spleen but predominant at epithelial surfaces. We have identified a subset of
      gamma delta T cells from weanling mice which is self reactive, i.e., these
      hybrids secrete IL-2 spontaneously, without antigenic stimulation or a
      requirement for APC. Self-reactive TCR-gamma delta+ hybrids and lines, all of
      which bear a particular TCR (V gamma 1.1C gamma 4V delta 6), have previously been
      derived from neonatal thymus and the skin. Northern blot and immunoprecipitation
      analyses suggest that the self-reactive IEL hybrids also bear a C gamma 4/V delta
      6 TCR. Antibody inhibition experiments showed that the self-reactivity of the IEL
      hybrids is TCR mediated. Spontaneous IL-2 production was blocked by soluble anti
      CD3 and anti-TCR-gamma delta antibodies but not by antibodies to the TCR-alpha
      beta. The self-reactive IEL hybrids lack class II MHC and the class I-like
      proteins CD1 and TLA but express class I MHC. IEL hybrids may also require the
      vitronectin receptor as an accessory molecule for their activation because
      spontaneous IL-2 production is blocked by antibody to the vitronectin receptor as
      well as by the extracellular matrix protein active site peptide RGDS, but not the
      control peptide RGES. V gamma 1.1C gamma 4V delta 6 T cells in the thymus, skin,
      and intestine may represent a small and unique subpopulation of lymphocytes with
      a potential for autoimmune reactivity at peripheral sites.

PMID- 1382096
TI  - Limited T cell receptor beta-chain usage in the sperm whale myoglobin 110-121/E
      alpha dA beta d response by H-2d congenic mouse strains.
AB  - The specificity and TCR gene usage of a panel of sperm whale myoglobin (SpWMb)
      reactive T cell clones from DBA/2 mice have previously been characterized, to
      study structure-function relationships between components of the ternary complex
      consisting of Ag, TCR, and MHC class II molecules, whose interaction leads to Th
      cell activation. These DBA/2 clones were specific for epitopes within the residue
      110 to 121 region of SpWMb, in the context of the mixed isotype molecule E alpha
      dA beta d, and expressed the TCR V beta 8.2 gene element. SpWMb-specific T cell
      hybridomas from the H-2d-congenic B10.D2 mouse strain, which differs from the
      DBA/2 strain only in the non-MHC background, were generated and compared with the
      T cell hybridomas from DBA/2 mice, in order to investigate the influence of non
      MHC genes on the specificity of the T cell response to the 110-121 epitope. V
      beta usage by these hybridomas was very homogeneous; three of three DBA/2 and
      eight of nine B10.D2 hybridomas specific for the 110-121 epitope, in the context
      of the mixed isotype molecule E alpha dA beta d, expressed the V beta 8.2 gene
      product. Nucleotide and amino acid sequences of D beta, J beta, and N regions
      were also similar. One 110-121/E alpha dA beta d-specific B10.D2 hybridoma used V
      beta 7, a V beta that is clonally deleted in DBA/2 mice. These experiments
      suggest that a similar set of TCR beta genes are used to respond to a given
      epitope, regardless of non-MHC background, and they support the hypothesis that,
      despite great variability between individuals in their non-MHC background genes,
      human HLA-associated diseases might result from the formation of a particular
      ternary complex consisting of a shared MHC molecule, a common "disease
      associated" epitope, and a shared TCR.

PMID- 1382097
TI  - Genetic mechanisms for dominant VH gene expression. The VHB512 gene.
AB  - A total of 37 mAb with reactivity for dextran B512 have been studied; 30 of them
      were products of independent rearrangements and 21 made use of the same VH gene,
      the VHB512 gene. These results unambiguously established that the immune response
      to dextran in the high responder mouse strain C57BL/6 was restricted. Idiotypic
      determinants are located all over the Ig V region. Many but not all Id described
      so far can be ascribed to protein structures encoded by VH or VL gene segments.
      The expression of the major Id, 17-9 Id, in C57BL/6 was not absolutely correlated
      with the expression of the dominant VHB512 gene in the same mouse strain.
      Inspection of amino acid sequences of the CDR3 of idiotypic positive and negative
      clones suggested that idiotypic structures may be associated with the expression
      of Tyr at position 95 and Phe or Leu at position 96 in the H and L chains,
      respectively. Therefore the indiscriminate use of idiotypic markers to
      characterize VH genes and the relevance of idiotypic regulation in VH gene
      expression are questioned. Id-positive and Id-negative clones displayed similar
      affinity values for dextran, indicating that idiotypic and binding structures
      were probably separated. The exchange of Asp65 for Gly65 in one of the clones
      reduced affinity for dextran, suggesting the involvement of CDR2 in dextran
      binding. The dominant expression of VH genes can be explained by somatic and/or
      genetic mechanisms. Because somatic mechanisms such as idiotypic regulation or
      selection based on affinity for dextran did not seem to influence the expression
      of the VHB512 gene we favor a genetic alternative. We discuss a model based on
      the distance between VH genes and D and JH elements. This model is compatible
      with somatic and genetic regulation in other systems and provides a new
      theoretical approach to the understanding of immune VH dominance and low
      responsiveness.

PMID- 1382098
TI  - VH restriction among human cold agglutinins. The VH4-21 gene segment is required
      to encode anti-I and anti-i specificities.
AB  - We previously reported that human autoantibodies with cold agglutinin activity
      contained a single human VH gene segment (VH4-21) which was also responsible for
      the cross-idiotypic specificity characteristic of the cold agglutinin response.
      To confirm and extend this observation we have analyzed at the nucleotide level
      the H and L chains of six new cold agglutinin molecules derived from different
      patients. We found that regardless of whether the antibody recognizes the i or
      the I red cell Ag, restriction at the VH gene segment level is absolute. We also
      found that even in the absence of somatic mutation the VH4-21 gene segment can
      encode both anti-i and anti-I specificities. Finally, although the VH4-21 gene
      segment is essential for cold agglutinin activity, the other genetic elements
      that contribute to the V region of the antibody molecules can be extremely
      diverse. The structural information provided in this report sharply restricts the
      requirement for encoding pathogenic cold agglutinin activity to one of the
      components of the H chain V region, specifically the VH gene segment. The
      implications of this apparently absolute requirement for a single VH gene
      segment, unprecedented in the human autoimmune response, are discussed.

PMID- 1382100
TI  - IFN increases class I MHC antigen expression on adenovirus-infected human cells
      without inducing resistance to natural killer cell killing.
AB  - It has been previously shown that unstimulated NK cells cannot preferentially
      lyse adenovirus serotypes 2 and 5-infected human cells. In this study, the
      ability of IFN to promote the selective NK cell-mediated lysis of adenovirus
      infected human cells was determined. The relationship between target cell
      susceptibility to NK cell-mediated killing and class I Ag expression was also
      analyzed through the use of adenovirus serotype 2 and 5 mutants that do not make
      the adenovirus early region 3 19-kDa class I binding protein. IFN induced the
      selective lysis of adenovirus serotype 2 and 5-infected human cells by activating
      NK cells (IFN-alpha) and protecting uninfected, but not adenovirus-infected
      cells, from NK cell-mediated lysis (IFN-gamma). IFN-gamma increased the
      expression of class I Ag on the surface of cells infected with the adenovirus
      early region 3 deletion mutants, dl327 or dl801, to a level equal to or greater
      than that expressed on uninfected cells. Despite the increased expression of
      class I Ag, IFN-gamma could not protect these adenovirus-infected cells from NK
      cell-mediated lysis. Thus, dl327 or dl801 infection prevented IFN-gamma's
      induction of cytolytic resistance to NK cell-mediated killing but left IFN
      gamma's induction of class I Ag intact. Surface class I Ag levels were
      substantially higher on IFN-gamma-treated, dl327-, and dl801-infected cells in
      comparison to cells infected with wild type adenovirus serotype 5. Again, higher
      target cell levels of class I Ag did not correlate with increased resistance to
      NK cell-mediated lysis because there was equivalent NK cell-mediated killing of
      IFN-gamma-treated adenovirus serotype 5-, dl327-, or dl801-infected cells. Thus,
      IFN-gamma only protects uninfected cells from NK cell-mediated killing,
      irrespective of target class I Ag levels, and thereby concentrates NK lytic
      activity on just adenovirus-infected cells. These data demonstrate that IFN
      gamma's ability to protect target cells from NK cell-mediated cytolysis is
      unrelated to IFN-gamma's induction of surface class I MHC Ag.

PMID- 1382099
TI  - Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating
      factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis
      factor-alpha.
AB  - Astrocyte-enriched populations were established from human embryonic brain
      analyzed for their ability to synthesize cytokines potentially relevant for
      mechanisms of inflammation and immunity in the brain. Unstimulated astrocytes did
      not secrete significant IL-6, IL-8, macrophage CSF (M-CSF), granulocyte
      macrophage CSF (GM-CSF), or granulocyte-CSF (G-CSF), as determined by specific
      ELISA and/or bioassay. With the exception of M-CSF mRNA, transcripts for the
      above factors were not detected in unstimulated astrocytes. On exposure of human
      astrocytes to IL-1 beta, high levels of IL-6, IL-8, M-CSF, G-CSF, and GM-CSF
      mRNAs were detected; moreover, active secretion of all the above cytokines was
      demonstrated. TNF-alpha was also able to stimulate IL-6, IL-8, M-CSF, GM-CSF, and
      G-CSF synthesis and secretion, but was generally less potent than IL-1 beta. No
      IL-3 mRNA or protein was detected in unstimulated or cytokine-treated astrocytes.
      IL-1 alpha and IL-1 beta mRNAs and proteins were not detected in unstimulated
      astrocytes, but were present in very small amounts after stimulation with TNF
      alpha/IL-1 beta. No IL-6, M-CSF, GM-CSF, G-CSF, or IL-8 were induced by IL-1 beta
      or TNF-alpha in early primary cultures, which mainly contain undifferentiated
      neuronal/glial progenitor cells. These studies demonstrate for the first time the
      production of multiple cytokines by normal human astrocytes stimulated in culture
      by IL-1 beta and TNF-alpha. The capacity of human astrocytes to synthesize and
      release cytokines active on hemolymphopoietic cells supports the concept that
      these cells play an important role in the regulation of inflammatory and immune
      responses in a variety of brain pathologies.

PMID- 1382101
TI  - Immunogenic properties of multiple antigen peptide systems containing defined T
      and B epitopes.
AB  - Immunization with chemically defined synthetic polymers, multiple Ag peptide
      (MAP) systems, containing T and B epitopes of the circumsporozoite protein of P.
      berghei induce high levels of circulating antibodies that are detectable several
      months after boosting. The anti-MAP secondary antibody response is characterized
      by an increase in the levels of circulating IgG and a concomitant decrease in the
      IgM levels. In vitro and in vivo experiments indicated that Th epitopes included
      in the MAP are recognized by T cells induced after immunization with the native
      protein and, also, that MAP-induced T cells can recognize the native protein. In
      addition to high levels of anti-B epitope antibodies, MAP immunization also
      induces antibodies against the T epitope. This anti-T epitope immune response
      does not affect the generation of the anti-B epitope antibodies. Immunization of
      different strains of mice revealed that the antibody response is consistent with
      the genetically restricted pattern of recognition of the T epitope. There are,
      however, significant differences in the levels of antibody responses observed
      among responder strains. The findings of this study indicate that MAP are potent
      immunogens capable of inducing immunologic memory and are, thus, good candidates
      for the development of subunit vaccines designed to induce high levels of
      circulating antibodies.

PMID- 1382102
TI  - Differential mapping of Fc gamma-binding and monoclonal antibody-reactive
      epitopes on gE, the Fc gamma-binding glycoprotein of herpes simplex virus type 1.
AB  - The entire 396 residue extracellular sequence of gE the HSV-1 Fc gamma-binding
      glycoprotein has been studied to determine epitopes binding to two mAb II-481 and
      88S previously demonstrated to react with gE at or near the Fc gamma-binding
      regions. Overlapping 7-mers constructed from the established sequence were tested
      with mAb II-481 and 88S along with their Fab fragments. Control mAb of the same
      IgG 2b subclass as well as whole rabbit and human IgG and Fc were also tested for
      binding to overlapping linear sequences using the ELISA pin assay to map Fc gamma
      binding regions. Six sequences PKTSWRRVS, GLYTLSV, QVASVVLVVQP, PAPPRSWP,
      CLYHPQLP, and ASTWTSRL were found that constituted major regions binding to the
      two different mAb of the same specificity. Glycine substitution for each residue
      within these sequences indicated that arginine 29, tryptophane 70, valine 144,
      valine 157, arginine 208, histidine 283, and arginine 305 constituted important
      portions of the II 481 mAb-reactive epitope. Many of the same regions along with
      one other, GPLHPSW, appeared to be involved in Fc gamma binding. Substitution of
      glycine for each residue indicated that histidine 67, tryptophane 70, valine 71,
      valine 157, valine 158, valine 160, valine 161, tryptophane 210, serine 279,
      cysteine 280, leucine 281, tyrosine 282, histidine 283, proline 284, glutamine
      285, proline 287, tryptophane 302, and arginine 305 were important for Fc gamma
      binding. Inhibition by gE peptides of rosetting of E sensitized with rabbit IgG
      antibody around HSV-1-infected cells, as well as inhibition of rosetting using
      F(ab)2 fragments of rabbit antibodies to these peptides was used to assay
      relative contributions of all seven regions to Fc gamma-binding activity. Our
      results provide a tentative map of mAb binding and Fc gamma-reactive sites on gE.
      mAb and Fc gamma binding of a limited number of individual antigenic amino acids
      widely distributed among the separate reactive regions suggest that many of the
      same separate residues contribute both to antigenicity as well as to Fc gamma
      binding activity.

PMID- 1382104
TI  - Conservation of signal transduction mechanisms via the human Fc epsilon RI alpha
      after transfection into a rat mast cell line, RBL 2H3.
AB  - The high affinity receptor for IgE (Fc epsilon RI) is present on mast cells and
      basophils, and the aggregation of IgE-occupied receptors by Ag is responsible for
      the release of allergic mediators. The Fc epsilon RI is composed of at least
      three different subunits, alpha, beta, and gamma, with the alpha subunit binding
      IgE. The series of biochemical events linking receptor aggregation to the release
      of mediators has not been fully delineated. As a step towards understanding these
      processes, and for the development of functional cell lines, we have transfected
      the human Fc epsilon RI alpha subunit into the rat mast cell line RBL 2H3. These
      human Fc epsilon RI alpha-transfected cell lines have been characterized with
      respect to the association of the human alpha subunit with endogenous rat beta
      and gamma subunits and the ability of aggregated Fc epsilon RI alpha subunits to
      mediate a variety of biochemical events. The signal transduction events monitored
      include phosphoinositide hydrolysis, Ca2+ mobilization, tyrosine phosphorylation,
      histamine release, and arachidonic acid metabolism. In all cases, the events
      mediated by aggregating human Fc epsilon RI alpha subunits were indistinguishable
      from those produced via the rat Fc epsilon RI alpha. These results demonstrate
      that the human Fc epsilon RI alpha subunit can functionally substitute for the
      rat Fc epsilon RI alpha subunit during signal transduction. The availability of
      this cell line will provide a means of evaluating potential Fc epsilon RI
      antagonists.

PMID- 1382103
TI  - Neutrophils, monocytes, and lymphocytes bind to cytokine-activated kidney
      glomerular endothelial cells through L-selectin (LAM-1) in vitro.
AB  - The role of L-selectin (LAM-1) as a regulator of leukocyte adhesion to kidney
      microvascular glomerular endothelial cells was assessed in vitro by using L
      selectin-directed mAb and an L-selectin cDNA-transfected cell line. The initial
      attachment of neutrophils, monocytes, and lymphocytes to TNF-activated bovine
      glomerular endothelial cells was significantly inhibited by the anti-LAM1-3 mAb.
      Under static conditions, anti-LAM1-3 mAb inhibited neutrophil adhesion by 15 +/-
      5%, whereas the anti-LAM1-10 mAb, directed against a functionally silent epitope
      of L-selectin, was without effect. The binding of a CD18 mAb inhibited adhesion
      by 47 +/- 6%. In contrast, when the assays were carried out under nonstatic
      conditions or at 4 degrees C, the anti-LAM1-3 mAb generated significantly greater
      inhibition (approximately 60%). CD18-dependent adhesion was minimal
      (approximately 10%) under these conditions. TNF-activated glomerular endothelial
      cells also supported adhesion of a mouse pre-B cell line transfected with L
      selectin cDNA, but not wild-type cells. This process was also inhibited by the
      anti-LAM1-3 mAb. Leukocyte adhesion to unstimulated endothelial cells was
      independent of L-selectin, but, after TNF stimulation, L-selectin-mediated
      adhesion was observed at 4 h, with maximal induction persisting for 24 to 48 h.
      Leukocyte adhesion was not observed if glomerular endothelial cells were exposed
      to TNF in the presence of RNA or protein synthesis inhibitors. Leukocyte
      attachment to TNF-activated glomerular endothelial cells was also partially
      inhibited by treatment of the cells with mannose-6-phosphate or phosphomannan
      monoester, a soluble complex carbohydrate, or by prior treatment of glomerular
      endothelial cells with neuraminidase, suggesting that the glomerular endothelial
      cell ligand shares functional characteristics with those expressed by lymph node
      and large vessel endothelial cells. These data suggest that TNF activation
      induced the biosynthesis and surface expression of a ligand(s) for L-selectin on
      glomerular endothelial cells, which supports neutrophil, monocyte, and lymphocyte
      attachment under nonstatic conditions.

PMID- 1382105
TI  - Importance of endothelial VCAM-1 for inflammatory leukocytic infiltration in
      vivo.
AB  - The microvascular endothelia of rejecting DBA/2----C57B1/6 murine cardiac
      allografts develop reactivity with the mAb M/K-2, which recognizes the murine
      homologue of the human leukocyte adhesion molecule VCAM-1. This reactivity does
      not develop in DBA/2----DBA/2 cardiac isografts or normal DBA/2 cardiac tissues.
      To determine whether endothelial VCAM-1 plays a role in allograft inflammation,
      cardiac allograft recipients were treated with M/K-2 antibody and monitored for
      leukocytic graft infiltration and graft survival. Treatment of the graft
      recipients with 200 micrograms/day M/K-2 Ig prolonged graft survival by 5 to 6
      days (statistically significant); whereas treatment with 100 micrograms M/K-2 Ig
      every other day after transplant did not influence graft survival. Neither
      treatment interfered with leukocytic infiltration, as detected histologically or
      by limiting dilution analysis. The high dose treatment, but not the low dose
      treatment, resulted in high circulating levels of M/K-2, as detected by serum
      ELISA, and prominent antibody deposition on the graft vascular endothelia, as
      demonstrated by immunohistologic analysis. These data demonstrate that VCAM-1 is
      uniquely expressed on the vascular endothelia of rejecting murine cardiac
      allografts, and that a mAb to VCAM-1 can interfere with the allograft rejection
      process. Although this antibody can interfere with lymphocyte-endothelial
      adhesion in vitro, it has little effect on leukocytic infiltration in rejecting
      allografts suggesting that this process does not depend exclusively on VCAM-1
      expression.

PMID- 1382106
TI  - Evidence for a human immunodeficiency virus type 1-mediated suppression of
      uninfected hematopoietic (CD34+) cells in AIDS patients.
AB  - Hematopoietic progenitor (CD34+) cells were purified from the bone marrow of 6
      human immunodeficiency virus (HIV) type 1-seropositive cytopenic patients and 10
      healthy donors. HIV-1-seropositive patients showed a reduced number of
      granulocyte/macrophage, erythroid, and megakaryocyte progenitors and also a
      progressive and significant decline of numbers of CD34+ cells in liquid culture,
      which did not result from a productive or latent HIV-1 infection of CD34+ cells.
      However, all HIV-1-seropositive patients showed signs of active viral replication
      at the bone marrow level. Moreover, virus isolates from 3 HIV-1-seropositive
      patients showed a dose-dependent inhibition on growth of normal CD34+ cells. This
      suppressive activity was almost completely reversed by incubating the virus
      isolates with an anti-gp120 polyclonal antibody before adding to normal CD34+
      cells.

PMID- 1382107
TI  - Intrafamilial transmission of hepatitis C virus: the important role of infections
      between spouses.
AB  - To investigate the intrafamilial transmission of hepatitis C virus (HCV) and
      related risk factors, anti-HCV antibodies in 186 family members of 48 index
      patients were studied. The index patients were anti-HCV-positive and had chronic
      liver disease. Overall, 10 family members (5.4%) were positive for anti-HCV,
      indicating a higher prevalence of anti-HCV among family members than among the
      Taiwanese general population. Spouses had the highest prevalence (21%) of anti
      HCV, with older age and longer duration of marriage of index patients the most
      evident risk factors. HCV RNA, recovered from the infected couples by reverse
      transcription-nested polymerase chain reaction and subsequently sequenced
      directly, was identical at the nucleotide level in 3 of the 4 couples studied,
      and the remaining couple had a homology of greater than 96%. These results
      strongly support that interspousal transmission may be the most important route
      of intrafamilial spreading of HCV, and thus sexual transmission, although with
      low efficiency, should be considered important in HCV infection.

PMID- 1382108
TI  - Modification of bleomycin-induced chromosome aberrations by hyperthermia and
      under energy depleting conditions in human peripheral lymphocytes.
AB  - Synergistic effects of bleomycin (BLM) and hyperthermia were studied in human
      peripheral lymphocytes (HPL). The frequencies of breaks produced by BLM were
      dependent on dose, incubation temperature, and treatment time. Heat alone did not
      induce chromosome aberrations. Synergistic effects of heat and BLM occurred at 43
      degrees C, either when hyperthermia was for 60 min following treatment with BLM
      or when hyperthermia was for 30 min simultaneously with BLM treatment. At
      incubation temperatures below 43 degrees C as many dicentric chromosomes as
      chromosome breaks were found, but about twice as many dicentric chromosomes as
      chromosome breaks were found when cells were treated with BLM at 43 degrees C for
      60 min. In all experiments with BLM chromosomal anomalies were overdispersed.
      Comparison with unstimulated HPL, heated after X-irradiation, suggested that heat
      inhibits repair of BLM-induced lesions to a smaller extent than X-ray-induced
      lesions. Experiments with sodium azide and 2-deoxyglucose led to the conclusion
      that cellular uptake of BLM is partly energy-dependent. Additionally, an energy
      independent uptake of BLM, which could not be blocked by inhibitors, was
      apparent.

PMID- 1382109
TI  - Acute phase reactant proteins--an aid to monitoring surgical treatment of
      laryngeal carcinoma.
AB  - The serum concentration of four acute phase reactant proteins (haptoglobin,
      sialic acid, alpha 1-antitripsin, ceruloplasmin) were determined in 160 patients
      with laryngeal cancer. In 50 cases treated by surgery serial determinations were
      performed. The control group included healthy persons and patients with non
      neoplastic diseases. The levels of haptoglobin, alpha 1-antitripsin and sialic
      acid were significantly higher in cancer patients than in control group. The
      levels of ceruloplasmin reveals no statistically significant difference between
      particular groups of patients. The serum concentrations of haptoglobin, alpha 1
      antitripsin and sialic acid correlated with the clinical status of cancer
      patients. We suggest that serial determination of certain acute phase reactant
      proteins may be useful as a prognostic acid in following patients with laryngeal
      carcinoma.

PMID- 1382110
TI  - Nucleolar organizer regions (NORs) and myoepitheliomas: a comparison with DNA
      content and clinical course.
AB  - Nucleolar organizer regions (NOR) were studied in 15 salivary gland
      myoepitheliomas by an argyrophilic staining technic (AgNOR). The AgNOR data were
      then compared with flow cytometric DNA content of the neoplasms and also with
      selected clinicopathologic parameters. We conclude that AgNOR's: (1) do not
      correlate well with DNA cytometric indices and (2) at best, provide redundant
      information.

PMID- 1382111
TI  - O-chain expression in the rough Brucella melitensis strain B115: induction of O
      polysaccharide-specific monoclonal antibodies and intracellular localization
      demonstrated by immunoelectron microscopy.
AB  - Spleen cells from mice infected with the rough Brucella melitensis strain B115
      were fused with NSO myeloma cells. Hybridoma supernatants were screened in ELISA
      with cell walls (CW), sonicated cell extracts (CE) and rough lipopolysaccharide
      (R-LPS) of B. melitensis strain B115 and whole B. melitensis B115 cells.
      Surprisingly, 22 monoclonal antibodies (mAbs) reacting in ELISA with both CW and
      CE but not with R-LPS and bacterial cells were shown by immunoblot analysis and
      ELISA to react with smooth lipopolysaccharide (S-LPS). These mAbs also reacted in
      ELISA with O polysaccharides (OPS) from the smooth Brucella abortus strain 99 and
      the smooth B. melitensis strain 16M and thus recognize epitopes present on the O
      chain. Proteinase K LPS preparations from B. melitensis B115 analysed by
      immunoblotting with one mAb (12G12) recognizing S-LPS of both A and M specificity
      displayed the typical S-LPS high-molecular-mass ladder pattern but no S-LPS was
      detected in the phenol/water/chloroform/light petroleum LPS preparation of the
      same strain. mAb 12G12, specific for S-LPS, and a mAb (A68/03F03/D05) specific
      for R-LPS were used to localize the O-chain and R-LPS expressed in B. melitensis
      strain B115 by immunoelectron microscopy. Immunogold labelling was observed at
      the surface of B. melitensis B115 cells with the anti-R-LPS mAb but not with the
      anti-S-LPS mAb. In ultrathin sections, immunogold labelling with the S-LPS
      specific mAb was observed in the cytoplasm and in the periphery of the cytoplasm,
      probably at the cytoplasmic membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382112
TI  - The role of lipopolysaccharide in the exposure of protective antigenic sites on
      the major outer membrane protein of Chlamydia trachomatis.
AB  - A species-specific monoclonal IgM antibody (mAb) 9BF8 directed against the major
      outer membrane protein (MOMP) of Chlamydia trachomatis neutralized several
      chlamydial serovars in a complement-independent manner. The presence of Mg2+ ions
      negated the neutralization in serovars F, L1 and L2, but not in serovars A, B, E,
      D and K. The ability of monovalent Fab-fragments of this mAb to neutralize
      chlamydial infectivity in a Mg-independent manner suggested that conformational
      alterations on the chlamydial surface induced by the cation hindered the IgM but
      allowed the smaller Fab fragment access to its epitope. In order to determine the
      chlamydial component that binds Mg, elementary bodies (EB) of serovars E and L1
      were treated with EDTA at pHs 8 and 9. The infectivity of the treated EB and the
      amount of released LPS were determined. Only after EDTA treatment at pH 9, as the
      LPS release increased, did the binding of the mAb on the chlamydial surface
      become Mg-independent. The infectivity of the EB was almost completely lost after
      such a treatment. These results suggest that the chlamydial LPS has the potential
      to modulate the exposure of antigenic sites on the MOMP, when it is cross-linked
      by Mg2+. They further imply that serovars protected by Mg and those that are not
      differ in the surface topology of one particular MOMP epitope, but are
      antigenically very similar. This difference might be of considerable importance
      in vivo.

PMID- 1382113
TI  - Immunochemical analysis and possible biological role of an Aeromonas hydrophila
      surface array protein in septicaemia.
AB  - The biochemical, immunological, and biological properties of an S layer purified
      from an Aeromonas hydrophila strain (AH-342) involved in a case of bacteraemia
      were investigated. The S layer selectively removed from the cell surface was
      composed of a single acidic (pI 4.56) protein subunit (surface array protein,
      SAP) with a molecular mass of approximately 52 kDa. Amino acid analysis of this
      52 kDa protein indicated a molecule composed of 498 amino acids with 46%
      hydrophobic residues. No cysteine residues were detected. The first 35 residues
      of the N-terminus were sequenced by Edman degradation; only 4-24% homology was
      noted between this sequence and those previously published for SAPs of Aeromonas
      salmonicida (A450) and a strain of A. hydrophila (TF7) originally isolated from a
      moribund fish. Polyclonal antibodies raised against AH-342 SAP were genospecific,
      reacting only against S layers produced by A. hydrophila strains and not those
      from Aeromonas veronii. Acute serum from the bacteraemic patient from whom AH-342
      was isolated reacted strongly with the SAP of AH-342 in immunoblot studies.
      Purified SAP, when intraperitoneally co-inoculated with SAP- strains of A.
      hydrophila into Swiss-Webster mice, could reduce the 50% lethal dose by
      approximately 30-70 fold. The results suggest that the SAP of A. hydrophila
      strains may play an important role in systemic dissemination after invasion
      through the gastrointestinal mucosa.

PMID- 1382114
TI  - The nucleotide sequence of the promoter, 16S rRNA and spacer region of the
      ribosomal RNA operon of Mycobacterium tuberculosis and comparison with
      Mycobacterium leprae precursor rRNA.
AB  - Mycobacterium tuberculosis H37Rv has a single rrn (ribosomal RNA) operon. The
      operon was cloned and a region of 1536 nucleotides was sequenced, starting 621 bp
      upstream from the 5'-end of the 16S rRNA coding region and continuing to the
      start of the 23S rRNA coding region. The 16S rRNA sequence inferred from the gene
      sequence was found to differ in one position from Mycobacterium bovis (nucleotide
      1443) and from Mycobacterium microti (nucleotide 427). A single putative promoter
      was identified on the basis of similarities with the sequence of rrn operons of
      Bacillus subtilis and Escherichia coli. The regions of similarity include a -35
      box, a -10 box, a stringent response element, antitermination signals, potential
      RNAase III processing sites and features of precursor rRNA secondary structure.
      Sequences upstream from the 5'-end of Mycobacterium leprae 16S rRNA were also
      investigated. Homologous schemes of secondary structure were deduced for
      precursor rRNA of both M. tuberculosis and M. leprae; although the principal
      features are common to both species there are notable differences.

PMID- 1382115
TI  - Glycoconjugates are stage- and position-specific cell surface molecules in the
      developing olfactory system, 1: The CC1 immunoreactive glycolipid defines a
      rostrocaudal gradient in the rat vomeronasal system.
AB  - Primary sensory neurons in the vomeronasal organ (VNO) project axons to the
      glomeruli of the accessory olfactory bulb (AOB) where they form connections with
      mitral cell dendrites. We demonstrate here that monoclonal antibodies to specific
      carbohydrate antigens define stage- and position-specific events during the
      development of the vomeronasal system (VN). CC1 monoclonal antibodies react with
      specific N-acetyl galactosamine containing glycolipids. In the embryo, CC1
      antigens are expressed throughout the VNO and on vomeronasal nerves. Beginning
      approximately at birth and continuing into adults, CC1 expression is spatially
      restricted in the VNO to centrally located cell bodies. In the postnatal AOB, CC1
      is expressed in the nerve layer and glomeruli, but only in the rostral half of
      the AOB. These data suggest that CC1 antigens may participate in the targeting of
      axons from centrally located VNO neurons to rostral glomeruli in the AOB. In
      contrast, CC2 monoclonal antibodies, which recognize complex alpha-galactosyl and
      alpha-fucosyl glycoproteins and glycolipids, react with all VNO cell bodies and
      VN nerves from embryonic (E) day 15 to adults. CC2 antibodies do not distinguish
      rostral from caudal regions of the AOB, nor are the CC2 glycoconjugates
      developmentally regulated. P-Path monoclonal antibodies, which recognize 9-O
      acetyl sialic acid, react with cell bodies in the VNO and nerve fibers from E13
      to postnatal (P) day 2. P-Path immunoreactivity disappears from the VNO system
      almost completely by P14, when only a few P-Path reactive nerve fibers can be
      seen. These studies suggest that specific cell surface glycoconjugates may
      participate in spatially and temporally selective cell-cell interactions during
      development and maintenance of vomeronasal connections.

PMID- 1382116
TI  - Antitumor activity of some metal complexes: effect on hepatic DNA, RNA, and
      protein synthesis in rats bearing transplanted tumors by Dalton's lymphoma cells.
AB  - In order to ascertain the antitumor properties of metal complexes, we have
      investigated their effect on hepatic DNA, RNA pools, and protein levels in rats
      bearing transplanted tumors by Dalton's Lymphoma cells because antitumor agents
      are directed against DNA, RNA transcription, and synthesis. These coordination
      complexes have been synthesized by the condensation of 2,6-diacetylpyridine with
      FaHh and DAP-Th2, thereafter they were complexed with nickel, cobalt, and iron.
      The structure of these metal complexes have been elucidated on the basis of IR,
      UV, NMR, Mass, EPR, and magnetic studies. The tumor-transplanted rats were
      treated with these metal complexes and ligands (2 ml of 1 mM sol/Kg body weight,
      s.c.) for two weeks to study their effect on DNA, RNA pools, and protein levels.
      The metal complexes have altered the hepatic DNA, RNA pools, and protein levels
      in the liver, kidney, and spleen of rats.

PMID- 1382117
TI  - Membrane currents of horizontal cells isolated from turtle retina.
AB  - 1. Membrane currents of horizontal cells isolated from the retina of the turtle,
      Pseudemys, were characterized by the whole-cell patch-clamp technique. 2. Four
      membrane currents were identified: an anomalous rectifier blocked by barium, a
      transient A-current, a sustained L-type calcium current enhanced by Bay K 8644,
      and a fast, tetrodotoxin-sensitive sodium current. Each of these four currents
      was found in both horizontal cell somata and axon terminals. 3. The current
      voltage relations of axon terminals and somata were similar, but, in the normal
      operating range of the cell (-30 to -50 mV), the mean slope resistance of the
      axon terminal was higher (1.38 G omega) than that of the soma (0.26 G omega). 4.
      Exposure to either glutamate, kainate, or quisqualate induced a sustained inward
      current in horizontal cell axon terminals. The reversal potential for this
      current was -3 mV when tested with voltage steps and +9.1 mV when measured by a
      voltage ramp. The same horizontal cells were insensitive to N-methyl-D-aspartate.
      5. A continuum model was developed to compute the degree of signal transfer
      between a horizontal cell body and its axon terminal. The model consisted of a
      network of electrically coupled somata that communicates with a network of
      electrically coupled axon terminals through the connecting axons. The specific
      membrane resistances used for the model derived from the patch-clamp measures. 6.
      We computed the voltage change elicited in either the layer of somata or of axon
      terminals by a static light stimulus of arbitrary dimensions. The amplitude of a
      spot response as a function of its radius was given by the weighted sum of two
      Bessel functions with different space constants. 7. The computed responses of the
      cell body were dominated by the Bessel function with the smaller space constant,
      whereas those of the axon terminal depended primarily on the Bessel function with
      the larger space constant. 8. The model predicts that, in contrast to the
      findings in teleost retina, there is little signal transfer between the somata
      and axon terminals of horizontal cell in the turtle retina.

PMID- 1382119
TI  - The functional anatomy of middle-latency auditory evoked potentials:
      thalamocortical connections.
AB  - 1. An 8 x 8-channel microelectrode array was used to map epicortical field
      potentials from a 4.375 x 4.375-mm2 area in the right parietotemporal neocortex
      of four rats. Potentials were evoked with bilaterally presented click stimuli and
      with electrical stimulation of the ventral and dorsal divisions of the medial
      geniculate body. 2. Epicortical responses to click stimuli replicated earlier
      findings. The responses consisted of a positive-negative biphasic waveform (P1a
      and N1) in the region of primary auditory cortex (area 41) and a positive
      monophasic waveform (P1b) in the region of secondary auditory cortex (area 36).
      Two potential patterns, one at the latency of the N1 and the other at the latency
      of the P1b, were used to represent activation of cells within areas 41 and 36. A
      linear combination of these patterns was sufficient to explain from 90 to 94% of
      the variance of the evoked potential complex at all latencies. 3. In the same
      animals, epicortical responses to electrical stimulation of the ventral and
      dorsal divisions of the medial geniculate body were also localized to areas 41
      and 36, respectively. A linear combination of potential patterns from these
      separate stimulation conditions was sufficient to explain from 80 to 93% of the
      variance of the original click-evoked potential complex at all latencies. 4.
      These data provide functional evidence for anatomically defined topographical
      thalamocortical projections to primary and secondary auditory cortex. They
      suggest that short-latency cortical evoked potentials (10-60 ms poststimulus) are
      dominated by parallel thalamocortical activation of areas 41 and 36.

PMID- 1382118
TI  - Nicotinic acetylcholine receptors are directly affected by agents used to study
      protein phosphorylation.
AB  - 1. Messenger RNAs for the subunits of the muscle nicotinic acetylcholine receptor
      (nAChR) were expressed in Xenopus oocytes. A two-electrode voltage clamp was used
      to measure the acetylcholine (ACh)-induced macroscopic currents. In addition,
      patch-clamp techniques were used to study nAChR channels in whole cells and in
      outside-out patches excised from BC3H-1 cells and in patches from oocytes. The
      single-channel and macroscopic currents were modified by compounds that are
      usually used to study protein phosphorylation. 2. IBMX (3-isobutyl-1
      methylxanthine) is a phosphodiesterase inhibitor. Because it elevates the
      intracellular concentration of adenosine 3',5'-cyclic monophosphate (cAMP), IBMX
      is often used to indirectly activate cAMP-dependent protein kinase. H-7 [1-(5
      isoquinolinylsulfonyl)-2-methylpiperazine] is mainly used as a rather nonspecific
      inhibitor of protein kinase activity. Both IBMX and H-7 directly inhibit ACh
      induced currents independent of their action on phosphorylation. This direct
      effect of these compounds is similar to the previously reported inhibition of
      nAChRs and K+ channels by forskolin, which is commonly used to elevate
      intracellular cAMP. 3. Macroscopic currents induced in the oocytes by 50 microM
      ACh had an average peak current of 605 nA, and the currents decayed
      biexponentially with tau of 15 and 225 s. When 300 microM H-7 was added
      simultaneously with the ACh, the average peak current was 228 nA and the tau were
      1 and 108 s. When 500 microM IBMX was added simultaneously with the ACh, the
      average peak current was 308 nA and the tau were 9 and 237 s. H-7 and IBMX
      decreased the peak current induced by ACh, and the compounds increased the decay
      rate of the current. Under these experimental conditions, the IC50 for reduction
      of peak amplitude at -30 mV was 160 microM for H-7 and 475 microM for IBMX. 4. H
      7 preferentially inhibits the open conformation of the nAChR channel, but there
      is also some inhibition of the closed channel. The inhibition is voltage
      dependent: inhibition decreases e-fold per 34 mV depolarization. H-7 does not
      become trapped within the closed channel and does not significantly alter
      desensitization under our experimental conditions. 5. H-7 and IBMX interrupt or
      terminate single-channel openings in membrane patches excised from oocytes or
      BC3H-1 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1382120
TI  - 5-HT modulation of hyperpolarization-activated inward current and calcium
      dependent outward current in a crustacean motor neuron.
AB  - 1. Serotonergic modulation of a hyperpolarization-activated inward current, Ih,
      and a calcium-dependent outward current, Io(Ca), was examined in the dorsal
      gastric (DG) motor neuron, with the use of intracellular recording techniques in
      an isolated preparation of the crab stomatogastric ganglion (STG). 2.
      Hyperpolarization of the membrane from rest with maintained current pulses
      resulted in a slow time-dependent relaxation back toward rest and a depolarizing
      overshoot after termination of the current pulse. In voltage clamp,
      hyperpolarizing commands negative to approximately -70 mV caused a slowly
      developing inward current, Ih, which showed no inactivation. Repolarization back
      to the holding potential of -50 mV revealed a slow inward tail current. 3. The
      reversal potential for Ih was approximately -35 mV. Raising extracellular K+
      concentration ([K+]o) from 11 to 22 mM enhanced, whereas decreasing extracellular
      Na+ concentration ([Na+]o) reduced the amplitude of Ih. These results indicate
      that Ih in DG is carried by both K+ and Na+ ions. 4. Bath application of
      serotonin (5-HT; 10 microM) caused a marked increase in the amplitude of Ih
      through its active voltage ranges. 5. The time course of activation of Ih was
      well fitted by a single exponential function and strongly voltage dependent. 5-HT
      increased the rate of activation of Ih. 5-HT also slowed the rate of deactivation
      of the Ih tail on repolarization to -50 mV. 6. The activation curve for the
      conductance (Gh) underlying Ih was obtained by analyzing tail currents. 5-HT
      shifted the half activation for Gh from approximately -105 mV in control to -95
      mV, resulting in an increase in the amplitude of Gh active at rest. 7. Two to 4
      mM Cs+ abolished Ih, whereas barium (200 microM to 2 mM) had only weak
      suppressing effects on Ih. Concomitantly, Cs+ also blocked the 5-HT-induced
      inward current and conductance increase seen at voltages negative to rest. In
      current clamp, Cs+ caused DG to hyperpolarize 3-4 mV from rest, suggesting that
      Ih is partially active at rest and contributes to the resting membrane potential.
      8. Depolarizing voltage commands from a holding potential of -50 mV resulted in a
      total outward current (Io) with an initial transient component and a sustained
      steady-state component. Application of 5-HT reduced both the transient and
      sustained components of Io. 9. Io was reduced by 10-20 mM tetraethylammonium
      (TEA), suggesting that it is primarily a K+ current.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1382121
TI  - Pharmacological properties of N-methyl-D-aspartate receptors on ganglion cells of
      an amphibian retina.
AB  - 1. The pharmacological characteristics of the N-methyl-D-aspartate (NMDA)
      receptors on amphibian retinal ganglion cells were studied to determine their
      similarities or differences from NMDA receptors found in mammalian central
      nervous system (CNS) cells. Cells were tested with a variety of NMDA antagonists
      acting at sites on the NMDA receptor/ion channel complex. 2. Whole-cell voltage
      clamp recordings were obtained from ganglion cells of the larval tiger salamander
      with a retinal slice preparation. All cells responded with inward currents (Vhold
      = -70 mV) when exposed to bath applications of NMDA, kainate (KA), and glutamate
      (GLU). NMDA currents reversed near 0 mV and showed a negative slope conductance
      region in the presence of external Mg2+. 3. NMDA-evoked inward currents could be
      blocked by application of 300 microM D-2-amino-7-phosphonoheptanoate (DAP7), 100
      microM Zn2+, 25 microM 7-chloro-kynurenate (7-cl-KYN), 1 microM MK-801, and 5 mM
      Mg2+. These results indicate that like mammalian NMDA receptors the amphibian
      NMDA receptor possesses binding sites for NMDA, glycine, zinc, dissociative
      anesthetics, and Mg2+. 4. NMDA responses were evoked in the presence of 1 mM
      extracellular Mg2+ in 100% of cells tested when held at -70 mV. Furthermore,
      there was a resting conductance at -70 mV and membrane current noise that could
      be attenuated by the application of NMDA-specific antagonists suggesting a tonic
      activation of NMDA receptors for cells at the resting potential.

PMID- 1382122
TI  - Evidence for nitric oxide synthase inhibitor-sensitive and insensitive
      hippocampal synaptic potentiation.
AB  - 1. Nitric oxide (NO) has been proposed as a retrograde messenger, mediating the
      postsynaptic to presynaptic transfer of the effects of conditioning stimulation,
      responsible for the initiation of hippocampal long-term potentiation (LTP). To
      further test this hypothesis, we inhibited nitric oxide synthase (NOS) to
      determine whether synaptic potentiation produced by different conditioning
      stimulus patterns and intensities was differentially affected by reduction of
      stimulation-dependent NO production. 2. Synaptic potentiation was produced in
      hippocampal slices from young F-344 rats by two different conditioning
      stimulation protocols. Conditioning stimuli were delivered to the Schaffer
      collateral commissural system, and moderate levels of potentiation of the
      population excitatory postsynaptic potential (EPSP) in area CA1 were produced by
      a single 100 Hz, 1-s conditioning train delivered at half-maximal stimulus
      intensity. Higher levels of potentiation of the population EPSP were obtained by
      delivering two 100 Hz, 1-s conditioning stimulus trains, with a 60-s intertrain
      interval, at high stimulus currents. 3. Application of the nitric oxide synthase
      inhibitors NG-nitro-L-arginine (NOARG; 0.1-200 microM) and NG-monomethyl-L
      arginine (NMMA; 100 microM) produced no significant direct effects on synaptic
      responses. 4. In slices that received a single conditioning stimulus train, both
      NOARG and NMMA were ineffective in blocking or reducing potentiation at
      concentrations between 0.1 and 200 microM. In slices receiving the more intense
      pair of conditioning stimulus trains, levels of potentiation in control slices
      were higher, and there was a very significant reduction by both NOARG (50 and 100
      microM) and NMMA (100 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382123
TI  - Expression of the period clock gene within different cell types in the brain of
      Drosophila adults and mosaic analysis of these cells' influence on circadian
      behavioral rhythms.
AB  - The product of the period (per) gene of Drosophila melanogaster is continuously
      required for the functioning of the circadian pacemaker of locomotor activity. We
      have used internally marked mosaics to determine the anatomical locations at
      which per expression is required for adult rhythmicity, and thus where the fly's
      circadian pacemaker is likely located in this holometabolous insect. We first
      provide a detailed description of the distribution and nature of per-expressing
      cells in the fly's CNS. Using an antibody to the per gene product, or to that of
      a reporter of per expression, in conjunction with an antibody to the embryonic
      lethal-abnormal visual system (elav) gene product--which is used as a marker of
      neuronal identity--we have experimentally confirmed previously proposed
      assignments of per-expressing cells to the neuronal and glial classes. Thus, we
      found that per expression and elav immunoreactivity colocalized in large cells
      located in the lateral cortex of the central brain, as well as in more dorsally
      located cells in the posterior central brain. In contrast, we found that cells
      located at the margins of the cortex and the neuropil, and within the neuropil,
      as well as smaller cortical cells found throughout the brain's cortex, were elav
      negative, supporting the notion that they are glial in nature. Using internally
      marked mosaics, we find that the pacemaker is located in brain but is not
      exclusive to the eyes, the ocelli, or the optic lobes, which is consistent with
      previous reports obtained in this and other insects of this class. Although the
      pacemaker may be a paired structure, we show that the functioning of one of them
      is sufficient for rhythmicity. Finally, we report that glial expression is
      sufficient for some behavioral rhythmicity to be manifest. However, the
      rhythmicities of animals for which per expression was confined to glia were weak,
      suggesting that neuronal per expression as well may be required for normal
      pacemaker function.

PMID- 1382124
TI  - Primary demyelination induced by exposure to tellurium alters Schwann cell gene
      expression: a model for intracellular targeting of NGF receptor.
AB  - Exposure of developing rats to tellurium results in a highly synchronous
      segmental demyelination of peripheral nerves with sparing of axons; this
      demyelination is followed closely by a period of rapid remyelination.
      Demyelination occurs subsequent to a tellurium-induced block in the synthesis of
      cholesterol, the major myelin lipid. We utilized the techniques of Northern
      blotting, in situ hybridization, and immunocytochemistry to examine temporal
      alterations in Schwann cell gene expression related to demyelination and
      remyelination. Tellurium-induced demyelination is associated with downregulation
      of myelin protein expression and a corresponding upregulation of NGF receptor
      (NGF-R) and glial fibrillary acidic protein (GFAP) expression. Steady-state mRNA
      levels (expressed on a "per nerve" basis) for P0, the major myelin protein, were
      decreased by about 50% after 5 d of tellurium exposure, while levels of mRNA for
      NGF-R and GFAP were markedly increased (about 15-fold). In situ hybridization of
      teased fibers suggested that the increase in steady-state mRNA levels for NGF-R
      was primarily associated with demyelinated internodes and not with adjacent
      unaffected internodes. Although P0 message was almost totally absent from
      demyelinating internodes, it was also reduced in normal-appearing internodes as
      well. This suggests that limiting the supply of a required membrane component
      (cholesterol) may lead to partial downregulation of myelin gene expression in all
      myelinating Schwann cells. In partially demyelinated internodes, NGF-R and GFAP
      immunofluorescence appeared largely confined to the demyelinated regions. This
      suggests specific targeting of these proteins to local areas of the Schwann cell
      where there is myelin loss. These results demonstrate that demyelination is
      associated with reversion of the affected Schwann cells to a precursor cell
      phenotype. Because axons remain intact, our results suggest that these changes in
      Schwann cell gene expression do not require input from a degenerating axon, but
      instead may depend on whether concerted synthesis of myelin is occurring.

PMID- 1382125
TI  - Childhood medical and behavioral consequences of maternal cocaine use.
AB  - Reviewed available studies of the impact of fetal cocaine exposure on child
      medical and developmental outcome, as well as the current status of clinical
      psychological interventions and research strategies. Current studies are
      inconclusive but suggest that prenatal exposure to crack-cocaine can have
      significant effects on the growth and neurological development of the infant,
      with the potential of later learning and behavioral disabilities. Social
      environmental correlates of maternal cocaine use are confounding factors with
      known negative effects on child outcome. Large, population-based studies using
      multivariate analyses are needed to determine the independent effects of cocaine
      on child outcome relative to other confounding variables.

PMID- 1382126
TI  - Transport and hydrolysis of maltose by Schwanniomyces castellii.
AB  - Hydrolysis and transport of maltose into Schwanniomyces castellii was studied
      under aerobic and anaerobic conditions. Amylase and glucosidase were not
      synthetized in presence of maltose in anaerobic conditions. Maltose permease was
      synthesized in anaerobiosis and its functioning is not inhibited. Glucose
      strongly repressed induction. The half-saturation constant for uptake of maltose
      was 0.06 mM. The rate of uptake of maltose was decreased by 2,4-dinitrophenol,
      antimycin or sodium azide. The significance of these results in relation to the
      Kluyver effect is discussed.

PMID- 1382127
TI  - Discrimination of multiple binding sites for antagonists of the calcium release
      channel complex of skeletal and cardiac sarcoplasmic reticulum.
AB  - The mechanisms by which ruthenium red (RR), neomycin and FLA 365 ([2,6-dichloro-4
      aminophenyl]isopropylamine) inhibit calcium channels of skeletal and cardiac
      sarcoplasmic reticulum (SR) are characterized. Neomycin and FLA 365 inhibit
      ryanodine-enhanced calcium release from skeletal SR vesicles in a dose-dependent
      manner. The apparent affinity of [3H]ryanodine is reduced in a dose-dependent
      manner by each inhibitor indicative of competitive mechanisms. Displacement
      studies with skeletal and cardiac SR demonstrate that the order of inhibitory
      potency is RR greater than neomycin greater than FLA 365 and RR greater than FLA
      365 greater than neomycin, respectively. Neomycin is 100-fold less potent in
      cardiac SR and inhibition of [3H]ryanodine binding is biphasic in both tissues.
      Neomycin induces a greater proportion of [3H]ryanodine binding states
      recalcitrant to inhibition in cardiac SR. The ability of neomycin to increase the
      apparent affinity of [3H]ryanodine for its binding sites is potentiated by RR and
      attenuated by FLA 365. Kinetic binding studies reveal that increasing neomycin
      concentrations decreases the association of [3H]ryanodine as predicted for
      competitive inhibition. However, high (much greater than Kn) neomycin increases
      [3H]ryanodine binding affinity by slowing dissociation of the radioligand
      demonstrating that, like micromolar ryanodine, neomycin induces allosterism.
      Studies with combinations of antagonists demonstrate the existence of two non
      overlapping inhibitor recognition sites within the ryanoid site, one polycationic
      inhibitor site and one FLA 365 inhibitor site. These results suggest that
      aminoglycoside-induced muscle paralysis may be mediated by direct block of pre-
      and postsynaptic calcium release channels of endoplasmic reticulum.

PMID- 1382128
TI  - Differential effects of glyburide on premature beats and ventricular tachycardia
      in an isolated tissue model of ischemia and reperfusion.
AB  - Possible anti- and proarrhythmic effects of glyburide, an ATP-sensitive K+
      channel blocker, were assessed in an isolated tissue model of reperfusion.
      Transmembrane electrical activity was recorded from endo- and epicardium of
      isolated segments of guinea pig right ventricular free walls, or two sites on
      papillary muscles with microelectrodes. An electrocardiogram was recorded by two
      electrodes placed at opposite ends of the tissue bath. Regular stimulation was
      delivered to endocardium. Tissues were exposed to simulated ischemia for 15 min
      and then were reperfused with normal Tyrode's solution. Rapid sustained or
      nonsustained ventricular tachycardia, bigeminy or trigeminy with characteristics
      of transmural re-entry occurred early in reperfusion in 50% of free walls.
      Triggered arrhythmias with characteristics of oscillatory afterpotentials
      (delayed afterdepolarizations) occurred in 20%. Arrhythmias were accompanied by
      prolongation of transmural conduction times and abbreviation of endocardial
      effective refractory periods and action potential durations. Glyburide (3 or 30
      microM) significantly attenuated abbreviation of action potential durations and
      effective refractory periods during ischemic conditions and early reperfusion.
      Neither endocardial nor transmural conduction times were modified by glyburide;
      however, glyburide significantly decreased the incidence of transmural conduction
      block during ischemic conditions. Glyburide abolished reperfusion arrhythmias
      with characteristics of re-entry, but potentiated oscillatory afterpotentials in
      papillary muscles and triggered arrhythmias with characteristics of oscillatory
      afterpotentials in free walls. Identical effects were seen with glyburide present
      in ischemic solution, or in both ischemic and reperfusion solutions, but no
      effect was observed with glyburide present only in reperfusion. Our study
      demonstrates possible cellular mechanisms underlying simultaneous pro- and
      antiarrhythmic drug effects exerted on late premature beats and rapid arrhythmias
      and closely coupled premature beats.

PMID- 1382129
TI  - Effect of the phospholipase A2 inhibitors quinacrine and 7,7
      dimethyleicosadienoic acid in isolated globally ischemic rat hearts.
AB  - Phospholipase A2 (PLA2) activity results in the formation of lysophospholipids
      and free fatty acids which may contribute to ischemic myocardial dysfunction. We
      evaluated the cardioprotective activity of two putative PLA2 inhibitors,
      quinacrine and 7,7-dimethyleicosadienoic acid (DEDA), in isolated globally
      ischemic rat hearts. Pretreatment with 1, 5 and 50 microM quinacrine before
      ischemia did not alter coronary flow but did cause significant cardiodepression.
      Twenty five minutes of global ischemia and 30 min of reperfusion caused severe
      myocardial dysfunction and lactate dehydrogenase release. Quinacrine
      significantly improved reperfusion contractile function and reduced lactate
      dehydrogenase release, indicative of cardioprotection. In contrast, 30 to 100
      microM DEDA produced neither preischemic cardiodepression nor cardioprotective
      activity. PLA2 inhibition was inferred from measurements of the prostacyclin
      metabolite, 6-keto-prostaglandin F1 alpha in the coronary effluent and myocardial
      palmitoyl-lysophosphatidylcholine. Quinacrine and DEDA reduced both 6-keto
      prostaglandin F1 alpha and palmitoyl-lysophosphatidylcholine by similar degrees.
      These results suggest that the cardioprotective activity of quinacrine is
      independent of PLA2 inhibition. A possible role of calcium inhibition was
      investigated in rat aortic smooth muscle strips. Norepinephrine-, KCl- and BAY
      K8644-induced contractions were antagonized in the presence of 5 and 50 microM
      quinacrine, but were unaffected by 30 to 60 microM DEDA. The ability of
      quinacrine to inhibit calcium was investigated further in cardiac ventricular
      myocytes. Measurement of mean whole cell calcium currents showed that quinacrine
      (5 microM) could inhibit this current up to 70%. Thus, these results suggest that
      quinacrine-induced cardioprotection may not be due to PLA2 inhibition, but may be
      related to calcium entry blocking activity.

PMID- 1382130
TI  - Constitutive and inducible nitric oxide synthases in human megakaryoblastic
      cells.
AB  - Human megakaryoblastic cells (Meg-01) were found to possess constitutive and
      express inducible nitric oxide (NO) synthase activities. The constitutive NO
      synthase was Ca+(+)- and NADPH-dependent, as is the NO synthase found previously
      in human platelets. Stimulation of Meg-01 cells by the cytokines interleukin-1
      beta (0.15-32.5 ng/ml) and tumor necrosis factor-alpha (0.15-10 ng/ml) resulted
      in expression of the inducible, Ca+(+)-independent, NO synthase. This activity
      was increased by the addition of NADPH, tetrahydrobiopterin and sepiapterin as
      cofactors. Induction of this enzyme was accompanied by a decrease in the
      constitutive NO synthase activity, a phenomenon which was prevented or reversed
      by dexamethasone (1 microM). Thus, human early differentiated megakaryocytic
      cells can synthesize NO from L-arginine by both the constitutive and the
      inducible NO synthases. These findings indicate that these enzymes may play an
      important biological role in megakaryocyte and platelet functions.

PMID- 1382131
TI  - Characteristics of a cytosolic arylacylamidase metabolizing thiacetazone.
AB  - The N-deacetylation of thiacetazone, an antitubercular drug possessing
      hepatotoxic side effects, by an exclusively cytosolic arylacylamidase has been
      identified in the liver and kidney of rat by monitoring the appearance of its
      metabolite p-aminobenzaldehydethiosemicarbazone spectrophotometrically. Studies
      toward its characterization in liver cytosol revealed that the hydrolase
      possesses a broad pH optimum ranging from 6.0 to 9.0. The Km and Vmax values for
      the N-deacetylation of thiacetazone are 5.7 x 10(-4) M and 0.123 nmol of p
      aminobenzaldehydethiosemicarbazone formed/min/mg cytosolic protein, respectively.
      The ability to metabolize thiacetazone was the same in the livers of cat, mouse
      and human, but lagged significantly in that of rat. Among the biodegradable
      esters examined as potential rivals of thiacetazone, only aspirin competitively
      inhibited thiacetazone hydrolysis (Ki = 2.1 x 10(-4) M). Discrimination of
      cytosolic thiacetazone N-deacetylase from nonspecific p-nitrophenylacetate
      esterase on the basis of their differential reactivity toward various inhibitors
      and activators disclosed that low concentrations of p-chloromercuribenzoate,
      AgNO3 and CuSO4 selectively undermine the activity of thiacetazone N-deacetylase,
      whereas SKF 525-A, ZnSO4 and FeCl3 are effective inhibitors of p
      nitrophenylacetate esterase. However, divalent ions (Ca++ and Mg++) and EDTA
      failed to alter the activity of the enzyme. Besides, thiacetazone metabolism was
      significantly retarded upon exposure to malathion. Notably, Nal/Kl stimulated the
      N-deacetylase activity as a function of iodide concentration. The hydrolysis of
      thiacetazone in the liver and kidney remained uninduced by phenobarbital, 3
      methylcholanthrene or benzo(a)pyrene (80 mg/kg, p.o., 8 days).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1382132
TI  - Effect of H1 receptor blockade on the early and late response to cutaneous
      allergen challenge.
AB  - We investigated whether cutaneous antigen-induced inflammatory cell infiltration
      and mediator release were modified by H1 receptor antagonists. Three chemically
      unrelated antihistamines (cetirizine, promethazine and chlorpheniramine) were
      tested in three groups of allergic subjects in a double-blind, crossover design.
      Chamber fluids were collected for 12 hr and histamine release, prostaglandin D2
      production and cellular infiltration were quantified. Cetirizine significantly
      decreased late leukocyte migration into antigen-challenged chambers: eosinophils
      by 68% (P less than .04), basophils by 64% (P less than .04) and neutrophils by
      72% (P less than .04), whereas mononuclear cells were not significantly affected.
      No alteration in the numbers of peripheral blood leukocytes or eosinophils
      occurred while on cetirizine treatment, suggesting that the decrease in
      inflammatory cells during the late phase reaction in the skin is not secondary to
      alterations in the peripheral leukocyte pool. In contrast, neither promethazine
      nor chlorpheniramine induced any significant alteration in inflammatory cell
      infiltration. All three antihistamines caused significant inhibition of the
      immediate reaction to antigen without any significant alteration in late phase
      reaction cutaneous reactivity. None of the three antihistamines caused any
      significant alteration in histamine or prostaglandin D2 levels. Thus, cetirizine
      may be an antihistamine uniquely capable of downregulating the late phase
      reaction inflammatory cell milieu without altering either early or late mediator
      production. The mechanisms involved and the clinical relevance of these findings
      remain to be explored.

PMID- 1382133
TI  - Synthesis and excitatory amino acid pharmacology of a series of heterocyclic
      fused quinoxalinones and quinazolinones.
AB  - As part of our program aimed at the development of potent excitatory amino acid
      antagonists, we synthesized and evaluated a series of substituted 1,2,4
      triazolo[4,3-a]quinoxalin-4(5H)-ones, 4, tetrazolo[1,5-a]quinoxalin-4(5H)-ones,
      5, and pyrazolo[1,5-c]quinazolin-5(6H)-ones, 6, and an imidazo[1,2-a]quinoxalin
      4(5H)-one, 7. In general, the same heterocycles which demonstrated the best
      affinity for the AMPA receptor also demonstrated the best affinity for the
      glycine site on the NMDA receptor complex. 1-Propyl-7,8-dichloro-1,2,4
      triazolo[4,3-a]quinoxalin-4(5H)-one, 4d, was found to bind with the greatest
      affinity to the AMPA receptor with an IC50 of 0.83 microM and antagonized 40
      microM AMPA-induced depolarization in the cortical slice preparation with an IC50
      of 44 microM. 7,8-Dichloro-1,2,4-triazolo[4,3-a]quinoxalin-4(5H)-one, 4a, and 7,8
      dichloroimidazo[1,2-a]quinoxalin-4(5H)-one, 7, possessed the best affinity for
      the glycine site with IC50 values of 0.63 and 1.26 microM, respectively. It is
      noteworthy that the SAR for the heterocyclic compounds did not directly parallel
      that of known quinoxalinediones (e.g. DNQX, 2, and DCQX, 15) at the AMPA receptor
      nor that of the kynurenic acids at the glycine site on the NMDA receptor complex.

PMID- 1382134
TI  - Atomic force microscopy of conventional and unconventional nucleic acid
      structures.
AB  - Images of conventional (Watson-Crick base paired) and unconventional (G4 RNA)
      nucleic acid structures have been obtained by atomic force microscopy. The images
      are reproducibly generated from samples deposited on freshly cleaved mica.
      Periodic substructural features are evident in fibres observed in both cases. In
      the case of G4 RNA, tip-induced formation of large fibres is observed.

PMID- 1382135
TI  - Insulin-like growth factor-I counteracts bFGF-induced survival of nitric oxide
      synthase (NOS)-positive spinal cord neurons after target-lesion in vivo.
AB  - We have used nitric oxide synthase (NOS) histochemistry as a perikaryal viability
      marker to trace the retrograde reaction of spinal cord intermediolateral (IML)
      sympathoadrenal projection (SAP)-neurons to target-removal, i.e., selective
      adrenomedullectomy and local administration of either insulin-like growth factor
      I (IGF-I), basic fibroblast growth factor (bFGF) or a combination of both.
      Counting of NOS-positive preganglionic spinal cord neurons 4 weeks post surgery
      indicated that more than 80% of stained neurons were lost from the IML-cell
      column. This percentage loss corresponds to the numerical loss of NOS-stained SAP
      neurons labeled retrogradely with Fast-blue prior to adrenomedullectomy. Basic
      FGF-supplementation at the site of lesion resulted in maintenance of the majority
      of NOS-positive IML-neurons, a finding confirmed by the survival rate of Fast
      blue prelabeled SAP-neurons. Thus, besides maintenance of the structural
      integrity of SAP-neurons, bFGF prevents loss of intracellular NOS-activity which
      may reflect unaltered cell metabolism (and function) of these neurons following
      target-removal in vivo. By contrast, IGF-I failed to alter the rate of
      disappearance of NOS-staining and labeling index of neurons within the IML-cell
      column postlesion, suggesting that IGF-I is not neurotrophic for SAP-neurons by
      itself. Combined treatment with both factors resulted in a more widespread loss
      of NOS-stained and Fast-blue-prelabeled SAP-neurons than registered after bFGF
      only treatment. No co-trophic effect of bFGF and IGF-I was evident; rather, the
      pronounced bFGF-induced rescuing effect was significantly suppressed by exogenous
      IGF-I in vivo, supporting the idea that this or another molecule induced by the
      treatment enhances rather than prevents retrograde degeneration and neuronal
      death within the adult lesioned IML-adrenal pathway.

PMID- 1382136
TI  - Alterations in slow transport kinetics induced by estramustine phosphate, an
      agent binding to microtubule-associated proteins.
AB  - Estramustine phosphate (EP) disassembles microtubules by binding to microtubule
      associated proteins (MAPs) rather than tubulin. In this study, EP-induced
      alterations of MAP integrity caused a unique form of axonal atrophy in rats.
      Initially, EP-induced axonal atrophy occurred in both proximal and distal axons
      of the sciatic nerve, characterized by an increase in neurofilament packing
      density, associated with a decrease in axonal area. In chronic exposure, distal
      axonal atrophy was associated with decreased numbers of microtubules, while the
      neurofilament number remained unaltered for the myelin spiral length. Continued
      exposure caused enlargement of proximal axons associated with an increase in
      neurofilament content. Correlative slow transport studies done at two different
      times, 7 and 14 days after [35S] methionine injection showed that EP retards the
      transport of cytoskeletal proteins migrating with both components of slow
      transport (SCa and SCb). However, there was a differential effect on SCb which
      showed progressive slowing along the nerve while the rate of SCa stayed
      relatively constant. In this model, the early occurring distal axonal atrophy can
      best be explained by reduced cytoskeletal components, particularly those
      traveling in SCb. Later in the course of intoxication, a relatively constant rate
      of SCa permitted continuous transport of neurofilament triplets, accounting for
      unaltered numbers of neurofilaments in distal axons with increased packing
      density. This model of axonal atrophy is unique because spacing of
      neurofilaments, not numbers determined axon size. Furthermore, EP-induced
      dissociation of the SCa and SCb kinetics suggests that MAPs play a role in the
      orderly, cohesive migration of slow transport components, essential for the
      normal organization of cytoskeleton.

PMID- 1382137
TI  - Sub-chronic exposure to opiates in the rat: effects on brain levels of substance
      P and calcitonin gene-related peptide during dependence and withdrawal.
AB  - Substance P (SP) and calcitonin gene-related peptide (CGRP) are putative
      transmitters in the central and peripheral (sensory) nervous systems. In this
      study, we examined the effects of dependence on and withdrawal from morphine and
      methadone on brain SP and CGRP content. Female Long Evans rats (70-100 g) were
      provided with plain drinking water or solutions containing opiate. No choice of
      drinking fluid was allowed. The maintenance level of each opiate (0.8 and 0.4
      mg/ml for morphine and methadone, respectively) was continued for 4 days.
      Following an injection with naloxone (10 mg/kg i.p.) or saline, animals were
      decapitated 0, 20, or 60 min later and regional brain peptide content was
      measured by specific radioimmunoassays. SP and CGRP content in opiate-maintained
      and naive animals were similar following saline injection. However, following
      naloxone injection in morphine-maintained animals, SP content was elevated in the
      hypothalamus and midbrain at 20 min, but by 60 min was no longer distinguishable
      from basal (0 min) level. CGRP content was increased in the medulla oblongata and
      followed a comparable time course but, unlike SP, was not altered in the
      hypothalamus or midbrain. No alterations were observed in methadone-maintained
      animals. These results correlated with the peak of the behavioral morphine
      withdrawal syndrome and were consistent with the comparatively milder abstinence
      encountered in methadone medication.

PMID- 1382138
TI  - Isolation and characterization of periaxolemmal and axolemmal enriched membrane
      fractions from the rat central nervous system.
AB  - In this report, we describe the fractionation of crude axolemmal fractions from
      rat lower brainstem into subfractions enriched in markers for either
      periaxolemmal myelin or axolemma. These subfractions were isolated on density
      gradients as bands layering on 0.8M and 1.0M sucrose. Both subfractions consisted
      of unilamellar vesicles. Relative to myelin purified from the same starting
      material, the 0.8M subfraction was enriched in MAG, CNPase, carbonic anhydrase
      and Na+, K+ ATPase but was extremely low in PLP and MBP. In addition, this
      fraction exhibited a protein profile distinct from myelin. The 1.0M fraction was
      also highly enriched in Na+, K+ ATPase and had an overall composition similar to
      the 0.8M subfraction. However, it differed from the 0.8M subfraction by being low
      in MAG, CNPase, and carbonic anhydrase, but enriched in voltage-dependent Na+
      channel, axon-specific fodrin, and MAP-1B. Based on these characteristics we
      concluded that the 0.8M and 1.0M subfractions were highly enriched in
      periaxolemmal myelin and axolemmal membrane, respectively. Plasmolipin10 was
      unique with equally high levels in myelin and in the 0.8M and 1.0M subfractions.
      Both subfractions were enriched, relative to myelin, in the alpha subunit of the
      GTP binding protein, Go, and the alpha subunit common to all G proteins, GA/1.
      Electrophysiology with membrane subfractions fused to lipid bilayers showed that
      both membranes contained sets of K+ and Cl- channels, which based on channel
      sizes and open times, are largely distinct from one another.

PMID- 1382139
TI  - Sickle cell/beta-thalassemia in North Jordan.
AB  - Clinical and haematological features of 50 patients with sickle cell/beta
      thalassemia (SB0 or SB+) are investigated. Total haemoglobin value was not
      significantly different (P greater than 0.05) in both types. Haemoglobin F and S
      were significantly higher (P less than 0.05) in SB0 than SB+ while haemoglobin A2
      level was lower in SB0 than SB+. One SB0 case with exceptionally high HbF (32 per
      cent) with severe clinical course was found. In this case, the high HbF did not
      ameliorate the clinical severity. Heterogeneity in each type of sickle cell/beta
      thalassemia is discussed. The differentiation of SB0 and sickle cell disease is
      best made on the basis of family study.

PMID- 1382140
TI  - Characterization of unintegrated retroviral DNA with long terminal repeat
      associated cell-derived inserts.
AB  - We have used a replication-competent shuttle vector based on the genome of Rous
      sarcoma virus to characterize genomic rearrangements that occur during retrovirus
      replication. The strategy involved cloning circular DNA that was generated during
      an acute infection. While analyzing a class of retroviral DNA clones that are
      greater than full length, we found several clones which had acquired nonviral
      inserts in positions adjacent to the long terminal repeats (LTRs). There appear
      to be two distinct mechanisms leading to the incorporation of cellular sequences
      into these clones. Three of the molecules contain a cell-derived insert at the
      circle junction site between two LTR units. Two of these molecules appear to be
      the results of abortive integration attempts, because of which, in each case, one
      of the LTRs is missing 2 bases at its junction with the cell-derived insert. In
      the third clone, pNO220, the cellular sequences are flanked by an inappropriately
      placed copy of the tRNA primer-binding site on one side and a partial copy of the
      U3 sequence as part of the LTR on the other side. A fourth molecule we
      characterized, pMD96, has a single LTR with a U5-bounded deletion of viral
      sequences spanning gag and pol, with cell-derived sequences inserted at the site
      of the deletion; its origin may be related mechanistically to pNO220. Sequence
      analysis indicates that all of the cellular inserts were derived from the cell
      line used for the acute infection rather than from sequences carried into the
      cell as part of the virus particle. Northern (RNA) analysis of cellular RNA
      demonstrated that the cell-derived sequences of two clones, pNO220 and pMD96,
      were expressed as polyadenylated RNA in uninfected cells. One mechanism for the
      joining of viral and cellular sequences suggested by the structures of pNO220 and
      pMD96 is recombination occurring during viral DNA synthesis, with cellular RNA
      serving as the template for the acquisition of cellular sequences.

PMID- 1382141
TI  - Monoclonal anti-idiotypes induce neutralizing antibodies to enterovirus 70
      conformational epitopes.
AB  - Monoclonal antibodies (MAbs) directed against the prototype enterovirus 70 (EV
      70) strain J670/71 were generated and characterized in order to produce anti
      idiotypic MAbs (MAb2s) for use as surrogate immunogens. Western immunoblot and
      radioimmunoprecipitation assays suggested that all the MAbs recognize
      conformational epitopes on the virion surface. An EV-70-neutralizing antibody,
      MAb/ev-12 (MAb1), was selected for the production of MAb2s. Five MAb2s were
      selected for their capacities to inhibit the interaction of MAb/ev-12 with EV-70
      in dot immunobinding inhibition and immunofluorescence assays. In addition, these
      five MAb2s inhibited virus neutralization mediated by MAb/ev-12, suggesting that
      they recognize paratope-associated idiotopes. In competition enzyme immunosorbent
      assays, none of the five MAb2s recognized other neutralizing and nonneutralizing
      EV-70-specific MAbs, demonstrating that the MAb2s were specific for private
      idiotopes. Immunization with each of the MAb2s was carried out for the production
      of anti-anti-idiotypic antibodies (Ab3). All five MAb2s induced an immune
      response. Moreover, results suggested that they share idiotopes, since MAb2
      MAb/ev-12 binding could be inhibited by homologous as well as heterologous Ab3s.
      Ab3 sera were shown to possess antibodies capable of immunoprecipitating 35S
      labeled viral proteins in the same manner as MAb/ev-12. Nine of 15 mice immunized
      with MAb2s demonstrated Ab3 neutralizing activity specific for the prototype EV
      70 strain, J670/71. The potential application of MAb2s to serve as surrogate
      immunogens for conformational epitopes is substantiated by the results presented
      in this report.

PMID- 1382142
TI  - Constitutive expression of human double-stranded RNA-activated p68 kinase in
      murine cells mediates phosphorylation of eukaryotic initiation factor 2 and
      partial resistance to encephalomyocarditis virus growth.
AB  - The cDNA encoding interferon-induced human double-stranded RNA-activated p68
      kinase was expressed in murine NIH 3T3 cells by using the pcDNA1/neo vector.
      Several stable clones were selected which expressed either the wild-type kinase
      or an inactive mutant possessing a single amino acid substitution in the
      invariant lysine 296 in the catalytic domain II. The transfected wild-type kinase
      showed properties similar to those of the natural kinase, such as subcellular
      ribosomal localization and dependence on double-stranded RNA for
      autophosphorylation. Upon infection with encephalomyocarditis virus (EMCV), wild
      type- but not mutant-expressing clones were found to partially resist virus
      growth. Such natural antiviral activity was virus specific, since no inhibition
      was observed in the case of vesicular stomatitis virus infection. In accord with
      EMCV inhibition, the wild-type p68 kinase was found to be highly phosphorylated
      during infection. Furthermore, its natural substrate, the small subunit of
      protein synthesis initiation factor eIF2, was phosphorylated. These results
      demonstrate that p68 kinase is activated during EMCV infection, leading to
      reduced virus production.

PMID- 1382143
TI  - Wild-type equine infectious anemia virus replicates in vivo predominantly in
      tissue macrophages, not in peripheral blood monocytes.
AB  - In situ hybridization of tissues from two horses infected with the wild-type
      Wyoming strain of equine infectious anemia virus (EIAV) identified the liver,
      spleen, lymph nodes, kidney, lung, and adrenal gland as the primary host tissue
      sites for viral transcription during acute infection. Combined
      immunohistochemistry, with a monoclonal antibody recognizing a cytoplasmic
      antigen of equine mononuclear phagocytes, and in situ hybridization for viral RNA
      identified most infected cells as mature tissue macrophages. In contrast, in situ
      hybridization of adherent peripheral blood mononuclear cells collected from
      horses on various days during the first 2 weeks postinfection with the Wyoming
      strain of EIAV failed to detect any viral RNA in these cells. For the two horses
      described here, serum reverse transcriptase activity correlated directly with the
      degree of replication detected in tissue macrophages on the day of sacrifice.
      These results suggest that unlike other lentivirus infections in which mature
      tissue macrophages accumulate cytoplasmic viral RNA to a high level but fail to
      produce infectious virions, mature tissue macrophages are the likely primary
      source of the high titer of viremia present during acute infection with EIAV. No
      significant posttranscriptional block of viral replication in tissue macrophages
      appears to occur with EIAV.

PMID- 1382144
TI  - Poliovirus-specific major histocompatibility complex class I-restricted cytolytic
      T-cell epitopes in mice localize to neutralizing antigenic regions.
AB  - A major histocompatibility complex (MHC) class I-restricted cytotoxic T
      lymphocyte (CTL) response is induced in BALB/c mice upon immunization with
      poliovirus serotype 1 (Mahoney strain). A similar class I-restricted response is
      also induced upon immunization with purified VP1 capsid proteins. Thus,
      poliovirus-specific MHC class I CTL responses can be induced independently of
      viral infection in murine hosts. In experiments using recombinant vaccinia virus
      vectors expressing different segments of the poliovirus capsid proteins and
      synthetic peptides, two regions of the VP1 capsid protein appear to contain
      epitopes recognized by this bulk CTL population. These epitope regions contain a
      Kd-restricted peptide-binding motif. Interestingly, each of these CTL epitopes is
      located near previously defined neutralizing antigenic sites.

PMID- 1382147
TI  - From the Centers for Disease Control. Update: cholera--western hemisphere, 1992.

PMID- 1382148
TI  - From the Centers for Disease Control. Update: eradication of paralytic
      poliomyelitis.

PMID- 1382145
TI  - Worldwide prevalence of lentivirus infection in wild feline species:
      epidemiologic and phylogenetic aspects.
AB  - The natural occurrence of lentiviruses closely related to feline immunodeficiency
      virus (FIV) in nondomestic felid species is shown here to be worldwide. Cross
      reactive antibodies to FIV were common in several free-ranging populations of
      large cats, including East African lions and cheetahs of the Serengeti ecosystem
      and in puma (also called cougar or mountain lion) populations throughout North
      America. Infectious puma lentivirus (PLV) was isolated from several Florida
      panthers, a severely endangered relict puma subspecies inhabiting the Big Cypress
      Swamp and Everglades ecosystems in southern Florida. Phylogenetic analysis of PLV
      genomic sequences from disparate geographic isolates revealed appreciable
      divergence from domestic cat FIV sequences as well as between PLV sequences found
      in different North American locales. The level of sequence divergence between PLV
      and FIV was greater than the level of divergence between human and certain simian
      immunodeficiency viruses, suggesting that the transmission of FIV between feline
      species is infrequent and parallels in time the emergence of HIV from simian
      ancestors.

PMID- 1382149
TI  - [Assessing the clinical significance of extrasystolic arrhythmias in healthy
      young people].

PMID- 1382146
TI  - Identification of a feline immunodeficiency virus gene which is essential for
      cell-free virus infectivity.
AB  - Feline immunodeficiency virus (FIV) contains at least three small open reading
      frames (ORFs) in the genome, in addition to the three structural genes. Two of
      these ORFs (putative vif and ORF-A) have unknown functions. Northern (RNA) blot
      analysis of mRNAs from an FIV-infected cell line showed that the putative-vif
      specific mRNA was expressed as a 5.2-kb species. To examine the function of the
      putative vif gene, we constructed mutants carrying a deletion in either the vif
      like gene or the rev gene from an infectious molecular clone of FIV. Although the
      vif mutant produced virion-associated reverse transcriptase at a normal level
      upon transfection, cell-free virus prepared from the transfected cells could not
      infect feline CD4+ cells. The infectivity of the vif mutant, however, was
      demonstrated in a coculture of the transfected cells and feline CD4+ cells. We
      conclude that FIV contains the vif gene, which is structurally and functionally
      similar to that of the primate lentiviruses.

PMID- 1382150
TI  - 3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the
      relevance of prenatal diagnosis in a 'new' type ('type 4').
AB  - The Mendelian disorder known as 3-methylgutaconic aciduria (McKusick 250950)
      gives evidence of allelic and locus heterogeneity. Type 1 has a mild clinical
      phenotype and confirmed 3-methylgutaconyl-CoA hydratase deficiency; inheritance
      is autosomal recessive. Other forms have major clinical manifestations and
      subdivide into X-linked (type 2), a form in Iraqi Jews with optic atrophy (so
      called type 3); and untyped (putative autosomal recessive) forms without
      identified enzyme defects. In the latter, 3-methylglutaconic aciduria may simply
      be a marker for another metabolic disorder. We describe a male proband with 3
      methylglutaconic aciduria designated here as 'type 4' (autosomal recessive, with
      severe psychomotor phenotype and cerebellar dysgenesis). He is the offspring of
      Italian consanguineous parents. Born with congenital malformations, he has been
      followed for 18 years, showing profound developmental delay and cerebellar
      dysgenesis. Measures of hydratase activity in cultured fibroblasts from the
      proband and 11 additional patients (two with type 1 disease, 9 with either type 2
      or an unspecified form) revealed deficient enzyme activity in type 1 cases and
      normal activity in the proband and the other 11 cases. Two of the untyped cases
      probably have 3-methylglutaconic aciduria of the type described here. Prenatal
      diagnosis in the form described here may be feasible by analysis of amniotic
      fluid metabolites in pregnancies at risk if the mother does not entirely remove
      elevated concentrations. A female sibling of the proband had normal metabolite
      values in amniotic fluid. Postnatal follow-up confirmed absence of the disease.
      We give the normal values for amniotic fluid and results on these additional
      fetuses at risk (none affected).

PMID- 1382151
TI  - Direct assessment of the role of NK cells in autoimmune diabetes.
AB  - Considerable indirect evidence implicates participation of natural killer cells
      (NK) in the pathogenesis of diabetes in BB rats. The most convincing evidence
      derives from studies showing that anti-CD8 antibody effectively prevents both
      primary disease onset and autoimmune damage to transplanted islets. However, anti
      CD8 treatment depletes both NK and cytotoxic T cells (CTL) since both cell types
      express the CD8 marker. To study directly the role of NK in diabetic BB rats we
      used MCA 3.2.3, a monoclonal antibody which selectively depletes normal Lewis
      rats of NK cells but not CTL. A regimen of ip injected antibody achieved rapid
      reduction of NK cells in diabetic and nondiabetic BB rats by FACS analysis. NK
      cell activity remained low in rats treated weekly as evidenced by YAC tumor cell
      killing. We next studied the effect of NK depletion on disease incidence in
      diabetes-prone BB rats of which about one half are expected to develop diabetes.
      Onset and incidence of diabetes in 3.2.3-treated and control antibody-treated
      aged matched litter mates were equal. These studies suggest that NK cells are not
      necessary for autoimmune islet destruction in spontaneously diabetic BB rats and
      support a role for CTL in pathogenesis of the disease.

PMID- 1382152
TI  - Mucosal glutamine utilization after small-bowel transplantation: an
      electrophysiologic study.
AB  - A short course of FK 506 after small bowel transplantation averts rejection in
      the rat and achieves indefinite survival of the recipient whose nutritional
      status is dependent on the function of the intestinal graft. Ex vivo
      electrophysiologic studies using the Ussing Cell were conducted to delineate
      functional competence of the graft by evaluating mucosal ion transport and
      glutamine utilization. Orthotopic small-bowel transplantation was performed in
      Lewis (LEW) rats as recipients of either Brown-Norway (BN) allografts or LEW
      syngeneic grafts. Allograft recipients received FK 506 either as a short course
      (2 mg/kg on Day 0-4 after transplantation) or continuously (2 mg/kg Day 0-4, then
      0.5 mg/kg weekly). Ileal mucosa was harvested from small bowel grafts 9 and 60
      days after transplantation and mounted in the Ussing Cell containing Hanks'
      balanced salt solution with/without L-glutamine (20 mM). Transmembrane potential
      difference (PD), which represents mucosal active ion transport, and mucosal
      resistance, an index of membrane integrity, were recorded. Nine days after
      transplantation, mucosal PD was the same in the ileum from syngeneic grafts,
      allografts treated with FK 506 and normal LEW and BN rats, and the addition of
      glutamine increased PD equally in all groups. In comparison, PD was markedly
      decreased in allografts undergoing rejection, and the glutamine response was
      blunted. Sixty days after transplantation, mucosal PD was reduced in allografts
      treated with a short course of FK 506, but normal in allografts receiving
      continuous immunosuppression with FK 506 and in syngeneic grafts. A decrease of
      mucosal resistance was not a feature of rejection nor a sequel of limited FK 506
      therapy. Our data indicate that allograft rejection results in a significant
      decrease in mucosal PD and a poor response to glutamine. Control of rejection by
      FK 506 preserves normal electrophysiologic responses of the allograft mucosa.

PMID- 1382154
TI  - ACE inhibitors and end-organ damage in cardiovascular disease: kidney and nervous
      system in hypertension. Proceedings of the Erasmus Medical Workshops.

PMID- 1382153
TI  - Intraoperative liver radiation after partial hepatectomy in a rat model.
AB  - Hepatic resection of metastatic tumor is a treatment option in selected patients.
      Resection margin is a prognostic factor of hepatic recurrence and survival.
      Although intraoperative radiation therapy (IORT) has been clinically useful in
      some gastrointestinal cancers, there is little information regarding its use
      following hepatic metastasectomy. In this study, a rat model was employed to
      evaluate histological changes and DNA synthesis as an indication of hepatic
      regenerative capacity following hepatectomy and liver IORT. All rats (N = 40) had
      a partial hepatectomy and were divided into four random groups: a nonradiated
      group and three groups of 1000, 2000, and 3000 cGy given by IORT. The only deaths
      occurred in the 3000 cGy group. Routine H and E staining of liver sections after
      3, 6, and 10 days suggested progressive hepatocyte damage notably in the 3000 cGy
      group. Comparison of the final average liver weights at 10 days confirmed a
      diminished liver mass in the 2000 and 3000 cGy animals. DNA synthesis in
      hepatocytes measured by [3H]-thymidine label incorporation 3, 6, and 10 days
      after hepatectomy and IORT indicated a comparative and overall decrease in Day 6
      peak activity between the three IORT groups. This study demonstrated delayed but
      substantial hepatic regeneration in the post-resected liver within the clinically
      useful IORT dose range (1000-2000 cGy) needed to control minimal residual tumor.
      This model has importance concerning the feasibility of IORT to the hepatic
      resection bed for patients where resection margins are inadequate.

PMID- 1382155
TI  - The interrelationships among filtration surface area, blood pressure, and chronic
      renal disease.
AB  - A primary role for the kidney in hypertension has long been recognized, but the
      pathogenetic interactions among renal hemodynamics, hormonal and hereditary
      factors, and dietary sodium intake remain ill defined. Reduction in the
      filtration surface area, whether acquired in the course of intrinsic renal
      disease or after surgical renal ablation, leads to systemic hypertension as well
      as to progressive renal insufficiency, sequellae made even more severe by dietary
      sodium excess. Moreover, hypertension and progressive renal disease occur in some
      individuals born with a solitary kidney, and occur almost invariably with more
      severe degrees of dysgenesis. Hypertension is also commonly observed in certain
      inbred rat strains in which the filtration surface area is congenitally
      deficient. Based on these and other lines of evidence reviewed herein, we
      postulate that a renal abnormality that contributes to essential hypertension in
      the general population is a reduced number of glomeruli and tubules, the
      consequences of which are limitations in the ability to excrete sodium and thus
      salt-sensitive hypertension. Furthermore, congenitally decreased filtration
      surface area may explain why only some, but not all, patients exposed to
      potentially injurious renal stimuli eventually manifest chronic nephropathy, and
      may also account for the susceptibility of subsets of type I and type II
      diabetics to develop overt glomerulopathy. Clinically, tests of renal reserve
      capacity may serve as a useful guide to identification of those patients at risk
      for the development of hypertension and progressive renal disease.

PMID- 1382156
TI  - Cognitive function and angiotensin-converting enzyme inhibitors in comparison
      with other antihypertensive drugs.
AB  - This review mainly considers randomized studies where angiotensin-converting
      enzyme (ACE) inhibitors were compared with other antihypertensive drugs in terms
      of objectively assessed cognitive function, subjectively evaluated cognitive
      function, work performance, and general vitality. An overall assessment of the
      data suggests that ACE inhibitors may improve performance on tests of alertness
      but it is unlikely that they produce either deleterious or beneficial effects on
      memory. On the other hand, methyldopa interferes with cognitive function and work
      performance. Propranolol was also associated with impairment of activity and
      satisfaction at work. In subjective evaluation of cognitive function, two trials
      suggest an increased reporting of impairment with nifedipine but this has not yet
      been confirmed. Vitality was reduced on both methyldopa and propranolol. It is
      concluded that the ACE inhibitors, in common with atenolol and verapamil, do not
      appear to have any major effects on cognitive function in hypertensive patients.

PMID- 1382157
TI  - Alpha-adrenergic and angiotensin II pressor sensitivity in hypertensive patients
      treated with an angiotensin-converting enzyme inhibitor.
AB  - We investigated pressor sensitivity to infused phenylephrine (PE), 0.05 to 0.4
      micrograms/kg/min, and angiotensin II (Ang II), 2.5 to 10 ng/kg/min, in 35
      patients with mild-to-moderate hypertension, before and at the end of a 4-week
      treatment period with the angiotensin-converting enzyme (ACE) inhibitor,
      cilazapril, 2.5 or 5.0 mg/day. Cilazapril lowered the mean systolic and diastolic
      blood pressure by 10.6/3.5 mm Hg, but had no effect on the dose-response curves
      of dose of PE or Ang II vs. the increase in systolic, diastolic, or mean blood
      pressure, or heart rate. There were also no significant effects of cilazapril on
      PD20 values, i.e., the dose of PE or Ang II required to increase mean arterial
      blood pressure (MAP) by 20 mm Hg, or on delta R-R/delta MAP (ratio of the
      increase of the ECG R-R interval to the increase in mean arterial blood pressure)
      as a measure of baroreflex sensitivity. Plasma renin activity was significantly
      increased by cilazapril therapy, but there were no changes in plasma
      concentrations of Ang II or atrial natriuretic factor. We conclude that
      cilazapril, an ACE inhibitor, does not alter alpha 1-adrenoceptor and Ang II
      receptor sensitivity to selective agonists, nor does it affect baroreflex
      sensitivity.

PMID- 1382158
TI  - Effects of chronic cilazapril treatment on cardiovascular control: a spectral
      analytical approach.
AB  - In 11 subjects with mild hypertension (sitting arterial pressure of 146 +/- 5/97
      +/- 2 mm Hg), the effects of chronic angiotensin-converting enzyme (ACE)
      inhibition (cilazapril, 5 mg p.o. once daily for 4 weeks) were studied at rest
      and during active standing by means of spectral analysis. Sympathetic vascular
      control was inferred from the power of the low-frequency (LF) component of the
      systolic arterial pressure (SAP) variability, assessed noninvasively with a
      plethysmographic technique. Simultaneously, quantitative indices of neural
      control of the sinoatrial (SA) node were obtained with the power of the LF and of
      the high-frequency (respiration linked) component of R-R variability. Before
      treatment, active standing produced a clear increase in the LF components of R-R
      and SAP variabilities. At the end of the 4 weeks of cilazapril treatment, the LF
      component of SAP variability during standing was significantly lower than prior
      to treatment, while the increase in the LF component of R-R variability was left
      unchanged. These findings suggest an inhibitory effect of chronic ACE inhibition
      upon vasomotor sympathetic control, as assessed non-invasively by this technique.

PMID- 1382159
TI  - Twenty-four-hour ambulatory noninvasive continuous finger blood pressure
      measurement with PORTAPRES: a new tool in cardiovascular research.
AB  - PORTAPRES model 1 is a portable 24 h continuous noninvasive blood pressure
      recorder based on the same principles as FINAPRES, the volume-clamp method of
      Penaz and the physiocal criteria of Wesseling. In addition, PORTAPRES measures
      two adjacent fingers in alternation every 30 min and automatically corrects
      hydrostatic effects due to height changes of the measured fingers. The device
      measures 255 x 210 x 60 mm and weights about 3,000 g, including a lithium battery
      pack and a TEAC cassette FM instrumentation tape recorder to record the finger
      pressure wave form, the height signal, and beat-to-beat derived systolic, mean
      and diastolic pressure as well as heart rate. It appears to be an excellent new
      tool for cardiovascular research in humans. In a randomized, placebo-controlled,
      double-blind, crossover study the effect of oral administration of 2.5 mg
      cilazapril, a new potent long-acting, nonsulfhydryl-group angiotensin converting
      enzyme (ACE) inhibitor, given once daily for 7 days, was investigated in 16
      healthy young men (mean age 25.3 +/- 1.6 years). Finger blood pressure and heart
      rate were measured with PORTAPRES for 24 h during everyday life and during
      standardized laboratory tasks, once about 1 to 2 h A.M. and once about 10 to 11 h
      P.M. once about 1 to 2 h A.M. and once about 10 to 11 h P.M. after drug
      administration. Physical activity was controlled by integrated thigh-EMG. Using
      stepwise multiple linear regression analysis it was shown that based on 64 s mean
      values, this measure of physical activity explains 34-77% of the heart rate
      variance within 24 h (median 53%), 10-52% (31%) of systolic, and 4-38% (25%) of
      diastolic blood pressure variance when up to 20 time lags of the EMG signal were
      introduced as possible predictors. This indicates that varying degrees of
      physical activity have a great impact on everyday blood pressure and heart rate.
      After one week cilazapril did not alter 24-h means of systolic and diastolic
      blood pressure or heart rate significantly, but reduced 30 min averages of both
      systolic and diastolic blood pressure by 6-10 and 4-6 mm Hg between 1 1/2 and 4
      or 6 h after drug administration respectively during everyday life (p = 0.0067
      0.066) without changing heart rate. On adjusting cardiovascular variables for the
      effects of physical activity, this blood pressure reduction was
      confirmed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1382160
TI  - Renoprotective action of angiotensin-converting enzyme inhibition in diabetes
      mellitus.
AB  - Roughly 40% of all diabetics, whether insulin dependent or not, develop
      persistent albuminuria, a decline in their glomerular filtration rate, and
      elevated blood pressure, i.e., diabetic nephropathy. Diabetic nephropathy is the
      single most important cause of end-stage renal disease in the Western world,
      accounting for over one-quarter of all end-stage renal disease.
      Systemic/glomerular hypertension plays a role in the initiation and progression
      of diabetic glomerulopathy. Angiotensin-converting enzyme (ACE) inhibitors are
      superior to conventional antihypertensive drugs in preventing the development of
      glomerular lesions in insulin-treated streptozotocin diabetic rats. Lowering of
      glomerular hypertension may be the crucial factor involved. Human studies suggest
      that ACE inhibitors postpone the progression to clinical overt diabetic
      nephropathy in normotensive diabetic patients with persistent microalbuminuria.
      ACE inhibitors combined with a diuretic reduce albuminuria and postpone renal
      insufficiency in hypertensive diabetics with overt nephropathy. No treatment
      modality other than antihypertensive treatment has yet been proven to be
      effective in protecting renal function in diabetic nephropathy. All previous
      reports dealing with the natural history of diabetic nephropathy have
      demonstrated a cumulative death rate between 50 and 77% 10 years after the onset
      of proteinuria. Effective antihypertensive treatment has reduced the cumulative
      death rate to 15-20% 10 years after the onset of nephropathy.

PMID- 1382161
TI  - Renal effects of angiotensin II in normotensive subjects on short-term cilazapril
      treatment.
AB  - In 13 normotensive subjects on a normal sodium diet, we studied renal vascular,
      blood pressure, and hormonal changes induced by infusion of exogenous angiotensin
      II (Ang II) (5 ng/kg/min) during baseline conditions and after 5 days of
      cilazapril administration. In both conditions, Ang II elicited a slight pressor
      response accompanied by renal hemodynamic and hormonal changes that were similar.
      This suggests that hourly changes in Ang II concentrations and/or in Ang II
      receptor density after short-term administration of the angiotensin-converting
      enzyme (ACE) inhibitor cilazapril does not significantly affect renal vascular
      reactivity. In addition, these results also indirectly suggest that most of the
      renal effects of ACE inhibition are mediated through suppression of Ang II
      formation.

PMID- 1382162
TI  - The antiproteinuric effects of blood pressure-lowering agents: differences
      between nondiabetics and diabetics.
AB  - The mechanism of the antiproteinuric effect of angiotensin-converting enzyme
      (ACE) inhibitors in diabetic and nondiabetic renal disease is as yet unknown. A
      meta-analysis of studies on the effects of ACE inhibitors and other
      antihypertensive drugs on proteinuria, blood pressure, and renal hemodynamics in
      nondiabetic renal disease revealed that ACE inhibitors lower proteinuria more
      than other antihypertensives. Moreover, a close correlation (p less than 0.01)
      between changes in urinary protein loss and in filtration fraction was found,
      whereas such a correlation could not be detected between changes in proteinuria
      and in blood pressure. This suggests that, at least in nondiabetic renal disease,
      the fall in proteinuria during ACE inhibition is the consequence of the
      intrarenal effect of the drug more than the systemic effect. Data on the
      mechanism of action of ACE inhibitors in diabetic microalbuminuria and in
      diabetic overt proteinuria are less consistent. A fall in proteinuria on
      antihypertensive drugs in these patients can be observed also without a
      significant fall in blood pressure, and without any change in filtration
      fraction. We therefore conclude that one should be cautious in extrapolating the
      data from studies in diabetic renal disease to patients with nondiabetic
      nephropathies. Moreover, we argue also that nonhemodynamic effects of ACE
      inhibitors also could be involved in the antiproteinuric effect of these drugs.

PMID- 1382163
TI  - Angiotensin-converting enzyme inhibition and diabetic nephropathy.
AB  - Hypertension and diabetes mellitus are strongly associated conditions from
      epidemiologic, genetic, and pathophysiologic points of view. The prevalence of
      hypertension is high in patients with diabetes, and, conversely, many patients
      with essential hypertension are glucose intolerant. Proteinuria appears in 40-50%
      of patients with insulin-dependent diabetes mellitus and 20-30% of patients with
      non-insulin-dependent diabetes mellitus. Progressive renal failure occurs in 30
      40 and 3-8% of patients, respectively, hypertension being a leading factor in its
      rate of progression. In various animal experiments, ACE inhibitors are able to
      prevent proteinuria and glomerular sclerosis, presumably by lowering
      transglomerular capillary pressure. In the diabetic human, ACE inhibitors are
      powerful antihypertensive drugs, devoid of metabolic side effects. Clinical
      studies indicate that ACE inhibitors reduce proteinuria and possibly slow the
      rate of decline in renal function. Such an effect is not observed with beta
      blockers. Large-scale studies are needed to confirm this very important
      hypothesis.

PMID- 1382164
TI  - Renal prostaglandin synthesis and angiotensin-converting enzyme inhibition.
AB  - Renal prostaglandins (PGs) help maintain renal blood flow and glomerular
      filtration rate when the kidney is exposed to a vasoconstrictor stress. In
      addition, they aid pressure natriuresis and blunt the antidiuretic effect of
      vasopressin. Angiotensin-converting enzyme (ACE) inhibitors could decrease renal
      PG synthesis by reducing angiotensin II (Ang II) formation or increase it by
      preventing kinin inactivation. Additionally, they could affect PG synthesis or
      catabolism directly. The effects of ACE inhibitors on blood pressure and renal
      hemodynamics appear to be largely independent of changes in renal PG synthesis.
      Similarly, there is no evidence that pressure natriuresis is modified by ACE
      inhibitors. A kinin induced increase in collecting duct PG synthesis may account
      for the water diuresis seen clinically with ACE inhibitors. A possible beneficial
      interaction between thromboxane synthesis inhibitors and ACE inhibitors may
      exist. Thromboxane synthetase inhibitors can reduce renal vascular resistance by
      redirecting PG endoperoxide synthesis toward prostacyclin. This effect may be
      offset by a prostaglandin-induced increase in renin release and Ang II formation.
      ACE inhibitors, by preventing Ang II synthesis, may increase the vasodilation due
      to thromboxane synthesis inhibition.

PMID- 1382165
TI  - Renal effects of antihypertensive agents in parenchymal renal disease and
      renovascular hypertension.
AB  - Treatment of hypertension by conventional antihypertensive medications usually
      has no significant effect on renal function in patients with essential
      hypertension and normal glomerular filtration rate. In this condition, new agents
      such as angiotensin-converting enzyme (ACE) inhibitors and calcium-channel
      blockers (CCBs) also do not appear to modify renal function. Reduction of
      arterial pressure is crucial for renal protection in patients with chronic renal
      disease and the effect of the new agents on the progression of renal failure
      remains unknown despite some promising reports. In patients with renovascular
      hypertension, mainly those with bilateral stenosis or stenosis of a solitary
      kidney, the use of ACE inhibitors may be associated with reversible renal
      deterioration, particularly in subjects with already impaired renal function and
      receiving diuretics. In this situation, reduction in arterial pressure by CCBs
      does not appear to lead to renal deterioration.

PMID- 1382166
TI  - The brain renin-angiotensin system: localization and general significance.
AB  - This report summarizes the present data about the existence of components of the
      renin-angiotensin system in the rat brain. Angiotensinogen mRNA, mas proto
      oncogene mRNA, angiotensin II (Ang II), and Ang II receptors have been mapped in
      the brain by using in situ hybridization, immunocytochemistry, and receptor
      autoradiography. These markers turned out to be widely distributed throughout the
      brain and to be not only restricted to areas related to cardiovascular control,
      but also to be present in functionally different areas, suggesting also other
      functions of angiotensin peptides. The distribution patterns of these components
      were correlated with data on the distribution of angiotensinogen, renin,
      angiotensin converting enzyme, and angiotensin fragments that revealed
      substantial topological mismatches. Using the model of "volume transmission,"
      possible explanations for these mismatches are proposed. In this regard, a
      possible involvement of angiotensin fragments and the mas proto-oncogene in the
      functioning of the brain renin-angiotensin system is also discussed,
      demonstrating the increasing complexity of this central regulatory system.

PMID- 1382167
TI  - Angiotensin-converting enzyme inhibition, angiotensin, and cognition.
AB  - In these studies, we have investigated possible cognition-enhancing effects of
      angiotensin-converting enzyme (ACE) inhibition, and putative neurochemical
      correlates for these actions. In a mouse habituation model, ACE inhibitors
      improved basal performance and antagonized scopolamine-induced deficits. The
      performance of aged mice and those with lesions of the nucleus basalis was also
      improved. ACE inhibition also improved scopolamine-impaired performance of rats
      in a swim-maze model. Neurochemical studies showed that a low dose (10
      micrograms/kg i.p.) of ceranapril caused significant alterations in ex vivo rat
      brain catecholamine levels in the nucleus accumbens, amygdala, and septum. In
      further studies, angiotensin II (Ang II) was shown to decrease potassium
      stimulated [3H] acetylcholine release from slices of rat entorhinal and human
      temporal cortex, an effect that could be antagonized by the angiotensin receptor
      antagonist [1-sar,8-thr]Ang II. It is concluded that ACE inhibition can improve
      both basal and impaired performance in animal models of learning, and that this
      improvement may be in part a consequence of the removal by ACE inhibition of an
      inhibitory tone on central acetylcholine release, and/or an effect on central
      catecholaminergic function.

PMID- 1382168
TI  - Role of brain angiotensin in cardiovascular regulation.
AB  - The brain is one of the organs where an intrinsic renin-angiotensin system (RAS)
      has been described. Stimulation of circumventricular or brainstem angiotensin II
      (Ang II) receptors engenders a distinct pattern of cardiovascular, endocrine, and
      behavioral responses featuring blood pressure increase, attenuation of the
      baroreceptor reflex, drinking, release of pituitary hormones such as vasopressin,
      oxytocin, and ACTH, and natriuresis. In contrast to most of the other central
      actions of Ang II, the natriuretic effect cannot be elicited by Ang II as a
      circulating hormone. Recently, we have shown that stimulation of Ang II AT-1
      receptors in the circumventricular organs causes a selective release of
      norepinephrine (NE) in the paraventricular nucleus (PVN) and in the supraoptic
      nucleus (SON). As vasopressin is also released from the PVN and SON, it is
      possible that the Ang II-NE interaction is involved in the release of
      vasopressin, thereby contributing to central blood pressure regulation and volume
      control. Finally, a substantial body of results suggests that an overactivity of
      the brain renin-angiotensin system is one of the contributors to genetic
      hypertension. However, this idea needs further confirmation.

PMID- 1382169
TI  - Diabetes and hypertension.
AB  - Arterial hypertension is more common in diabetes mellitus than in nondiabetic
      subjects, and many metabolic and hemodynamic features of diabetes mellitus
      contribute to the etiology of hypertension. Control of hypertension in diabetes
      mellitus is extremely important as high blood pressure accelerates both
      macrovascular and microvascular complications of this disease. Most classes of
      antihypertensive agents are effective in blood pressure control in diabetes
      mellitus, so the choice of antihypertensive therapy is based on the differences
      in adverse effects of these agents on metabolic control and their effect on other
      cardiovascular risks.

PMID- 1382170
TI  - Interaction between the renin-angiotensin-aldosterone and sympathetic nervous
      systems.
AB  - The renin-angiotensin-aldosterone system is mainly involved in the regulation of
      arterial blood pressure and fluid balance. One of the main stimuli for the
      secretion of renin present in the renal juxtamedullary cells, but also in some
      other tissues, is provided by the sympathetic nervous system via the action of
      norepinephrine on beta 1-adrenoceptors. There is good evidence in animal
      experiments that angiotensin II (Ang II) facilitates sympathetic
      neurotransmission by several mechanisms, all of which seem to involve distinct,
      but perhaps heterogeneous, Ang II receptors. Acting within the central nervous
      system, angiotensin augments sympathetic nerve outflow directly, but probably
      also by inhibiting the reflex decrease in sympathetic nerve activity following an
      increase in arterial pressure. Ang II also stimulates adrenomedullary and
      ganglionic transmission as well as enhances the release of sympathetic
      transmitter by a presynaptic action. In addition, there is some evidence that
      angiotensin can inhibit norepinephrine reuptake and augment its biosynthesis and
      responses mediated via both extrasynaptic alpha 2- and intrasynaptic alpha 1
      adrenoceptors. Angiotensin-converting enzyme inhibitors, particularly when the
      endogenous renin-angiotensin activity is high, attenuate sympathetic
      neurotransmission. Despite a clear demonstration that the renin-angiotensin
      system augments the activity of the sympathetic nervous system in animals,
      evidence for such a role in humans is tenuous. This is probably mainly due to the
      difficulty in quantitatively monitoring and assessing the autonomic function in
      humans. It is possible that in congestive heart failure, where the renin
      angiotensin system can be highly activated, sympathetic facilitation by
      angiotensin as well as its attenuation by converting enzyme inhibitors may be
      important.

PMID- 1382171
TI  - Regulation of cerebral blood flow in health and disease.
AB  - A review is given of the normal regulation of cerebral blood flow (CBF) and its
      pathophysiology in hypertension and stroke. In otherwise healthy hypertensive
      patients, the absolute level of CBF is the same as in normal subjects. CBF
      autoregulation, however, is shifted towards higher pressure, thus impairing the
      tolerance to hypotension. In most patients, this does not interfere with the
      beneficial effect of treatment, i.e., stroke prevention. Cerebral ischemia,
      however, may be provoked by overzealous pressure lowering in selected clinical
      settings: initial or intensified treatment of very severe hypertension, treatment
      of hypertension in the elderly, and treatment of hypertension in acute stroke. In
      the latter, a complicated sequence of brain ischemia and hyperemia makes
      antihypertensive intervention difficult in the early phase, when blood pressure
      is probably best allowed to decrease spontaneously.

PMID- 1382172
TI  - Protective effect of cilazapril on the cerebral circulation.
AB  - The goal of an antihypertensive treatment is to prevent "end-organ" damage.
      Cerebral vascular complications are among the most important because they are
      life threatening and can occur even at an early stage of the disease. Recently,
      it has been shown that cilazapril can decrease the mortality of stroke-prone
      rats, suggesting a decrease in the incidence of strokes, which occur
      spontaneously in these animals. The present article reviews the different
      functional and morphological changes that may explain the cerebral protective
      effects of cilazapril, such as the normalization of cerebral vascular reserve,
      decrease in the media, increase in the external diameter, and normalization of
      the mechanics and endothelial function of cerebral arterioles. In addition, the
      inhibition by cilazapril of injury-induced proliferation of smooth muscle cells
      and the infiltration of the endothelium by macrophages could prevent the
      development of atherosclerosis.

PMID- 1382173
TI  - Immunocytochemical detection of factor XIII A--subunit in acute leukemia.
AB  - Factor XIII (FXIII) is a plasma pro-transglutaminase consisting of A and B
      subunits in a tetrameric structure. A cellular form of FXIII consisting
      exclusively of A subunits exists in platelets and monocytes: monocyte FXIII may
      be involved in connective tissue organization. To evaluate the expression and
      diagnostic significance of FXIII A subunit (FXIIIA) in acute leukemia, we
      performed an immunocytochemical study (PAP technique) with rabbit antiserum
      against FXIIIA on leukemic blasts of 48 cases. FXIIIA was detected only in
      myelomonocytic (M4), monocytic (M5) and megakaryocytic (M7) cases: in M4 and M5
      samples the amount of blast cytoplasmic FXIIIA was closely correlated with the
      expression of monocyte-specific antigenic and cytochemical markers. Our data show
      immunocytochemical detection of FXIIIA to be useful for acute leukemia
      characterization.

PMID- 1382174
TI  - Single-channel and whole-cell recordings from non-dissociated sympathetic
      neurones in rabbit coeliac ganglia.
AB  - A procedure is described for performing patch-clamp recordings on mammalian
      sympathetic neurones within intact ganglia. The plasma membrane of superficial
      neurones was cleaned by blowing (1.5-3 h) a gentle stream of Ringer saline onto
      ganglia, the connective sheath of which was previously softened by a short
      protease treatment. This procedure preserved the intraganglionic connectivity so
      that the neurones could be activated either synaptically or antidromically by
      stimulating the appropriate nerves. Depending on the duration of the mechanical
      cleaning step, recordings were performed on either the neurones or the satellite
      glial cells covering the neuronal cell bodies. The applicability of the various
      configurations of the patch-clamp technique to studying sympathetic neurones is
      illustrated by recordings of whole-cell voltage, whole-cell currents and single
      channel currents in cell-attached and excised patches. With these techniques, the
      resolution of the membrane current recordings is higher than with conventional
      microelectrodes. The results obtained show that mammalian sympathetic neurones
      have a very high input resistance (0.5 G omega), are electronically compact and
      may display pacemaker activity. These techniques provide a useful tool for
      studying the synaptic transmission and neuromodulation mechanisms operating
      within the sympathetic ganglia.

PMID- 1382175
TI  - A computerized 2-dimensional vibrating probe for mapping extracellular current
      patterns.
AB  - We describe a computer-assisted 2-dimensional vibrating probe system for mapping
      endogenous electric current patterns in biological preparations. This system
      overcomes some of the main limitations of the original 1-dimensional vibrating
      probe design and adds several new capabilities. Two piezo-electric bender
      elements mounted perpendicularly are used to vibrate the probe in a circle by
      applying 2 sine waves (1 to each element) that are 90 degrees out-of-phase with
      each other. The circular rotation of the probe allows it to detect simultaneously
      the 2 orthogonal components of a current in the horizontal plane. The voltages
      measured by the probe are digitized and analyzed by a computer and are used to
      calculate a current vector. A graphical representation of the current vector is
      then superimposed on a video image of the experimental preparation. This probe
      system responds to known currents in the expected manner and exhibits a low
      inherent noise level. Also included in this paper are some preliminary
      measurements made with this instrument on neurulating Xenopus embryos and on
      transected larval sea lamprey (Petromyzon marinus) spinal cords.

PMID- 1382176
TI  - Effect of different convulsants on calmodulin levels and proto-oncogene c-fos
      expression in the central nervous system.
AB  - In the present study, a relationship between convulsant activity and two cellular
      events, changes in calmodulin (CaM) concentration and proto-oncogene c-fos
      expression has been considered. c-fos has been found activated after the
      administration of the organochlorine insecticide lindane, the Ca2+ channel
      agonist Bay K, and N-methyl-D-aspartate (NMDA). The administration of the voltage
      dependent Ca2+ channel antagonist nifedipine was able to block the expression
      elicited by lindane. The effect of lindane on c-fos expression could not be
      blocked by prior administration of MK-801, a non-competitive antagonist of the
      NMDA receptor. These results suggest a possible role for the voltage-dependent
      Ca2+ channels in the mechanism of action of lindane. By means of in situ
      hybridization, the different patterns of c-fos expression after the
      administration of the mentioned compounds have been described. A possible
      modification of the levels of CaM has also been investigated. Among all the
      subcellular fractions considered, only levels of nuclear CaM appeared to be
      affected after the different treatments. The changes observed seemed to follow a
      similar pattern to that described for c-fos induction. Calcium entry through
      these voltage-dependent calcium channels would be the link between membrane
      depolarizing events and expression of c-fos and/or increase in nuclear CaM.

PMID- 1382177
TI  - Altered amounts of G-protein mRNA and cAMP accumulation after long-term opioid
      receptor stimulation of neurons in primary culture from the rat cerebral cortex.
AB  - Primary neuronal enriched cultures were incubated with mu (morphine, 10(-5) M),
      delta (DPDPE, 10(-6) M) and kappa (U-50,488H, 10(-5) M) receptor agonists for 5
      days, respectively. Thereafter the acute inhibitory actions of mu, delta or kappa
      receptor agonists on forskolin stimulated cAMP accumulation was assayed. The
      effect of long term opioid treatment on the steady-state level of G-protein mRNA
      (G alpha s, G alpha i-1 and G alpha i-2) was analyzed using an RNAase protection
      hybridization assay. Incubation for 5 days with kappa receptor agonist resulted
      in an attenuated ability to decrease the accumulation of cAMP by kappa receptors,
      as well as mu and delta receptors, which was also observed after 5 days of
      incubation with the delta receptor agonist. Furthermore, the adenylate cyclase
      responsiveness to forskolin stimulation was markedly reduced in cultures treated
      with either delta or kappa receptor agonists. Five days of incubation with kappa
      receptor agonist resulted in an increase in the levels of G alpha s and G alpha i
      2 mRNAs. No effects on the amounts of G alpha s mRNA, G alpha i-1 mRNA or G alpha
      i-2 mRNA were detected after 5 days of delta receptor stimulation. On the other
      hand, 5 days of mu receptor stimulation decreased the amounts of G alpha s, G
      alpha i-1 and G alpha i-2 mRNA. Incubation with kappa receptor agonist for 24 h
      resulted in a significant decrease in the forskolin-stimulated accumulation of
      cAMP. The stimulatory effect of forskolin was further decreased after 3 days
      incubation with kappa receptor agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382178
TI  - Chronic administration of NMDA antagonists induces D2 receptor synthesis in rat
      striatum.
AB  - Dopamine D2 receptor gene expression was examined in rat striatum after chronic
      treatment with N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine at 15
      mg/kg/day or MK-801 at 0.1, 0.2 and 0.4 mg/kg/day per os, for 50 days). The long
      isoform mRNA, as well as the total D2 mRNA expression were induced. No change was
      noticed in striatal dopamine release or turnover. D2 binding studies carried out
      in MK-801 chronically treated (0.3 mg/kg/day per os, for 50 days) and control
      rats revealed an increased receptor density in treated animals without a
      significant change in receptor affinity. These results suggest that the synthesis
      of both striatal D2 receptor isoforms is postsynaptically regulated at the
      transcriptional level, by events triggered by glutamate through the NMDA-type
      receptor.

PMID- 1382180
TI  - Ion channels.

PMID- 1382179
TI  - Rate and mode differences between nuclear and mitochondrial small-subunit rRNA
      genes in mushrooms.
AB  - Sequences from homologous regions of the nuclear and mitochondrial small-subunit
      rRNA genes from 10 members of the mushroom order Boletales were used to construct
      evolutionary trees and to compare the rates and modes of evolution. Trees
      constructed independently for each gene by parsimony and tested by bootstrap
      analysis have identical topologies in all statistically significant branches.
      Examination of base substitutions revealed that the nuclear gene is biased toward
      C-T transitions and that the distribution of transversions in the mitochondrial
      gene is strongly effected by an A-T bias. When only homologous regions of the two
      genes were compared, base substitutions per nucleotide were roughly 16-fold
      greater in the mitochondrial gene. The difference in the frequency of length
      mutations was at least as great but was impossible to estimate accurately because
      of their absence in the nuclear gene. Maximum likelihood was used to show that
      base-substitution rates vary dramatically among the branches. A significant part
      of the rate inconstancy was caused by an accelerated nuclear rate in one branch
      and a retarded mitochondrial rate in a different branch. A second part of the
      rate variability involved a consistent inconstancy: short branches exhibit ratios
      of mitochondrial to nuclear divergences of less than 1, while longer branches had
      ratios of approximately 4:1-8:1. This pattern suggests a systematic error in the
      branch length calculation. The error may be related to the simplicity of the
      divergence estimates, which assumes that all base positions have an equal
      probability of change.

PMID- 1382181
TI  - Prevention of rundown in electrophysiological recording.

PMID- 1382182
TI  - Patch voltage clamping with low-resistance seals: loose patch clamp.

PMID- 1382183
TI  - Patch-clamping cells in sliced tissue preparations.

PMID- 1382184
TI  - Preparation of RNA for injection into Xenopus oocytes.

PMID- 1382185
TI  - Tissue RNA as source of ion channels and receptors.

PMID- 1382186
TI  - Patch clamp techniques: an overview.

PMID- 1382187
TI  - In vitro synthesis of RNA for expression of ion channels in Xenopus oocytes.

PMID- 1382188
TI  - Electrophysiological recording from Xenopus oocytes.

PMID- 1382189
TI  - Use of stage II-III Xenopus oocytes to study voltage-dependent ion channels.
AB  - Stage II-III Xenopus oocytes represent a useful extension of the standard Xenopus
      oocyte expression system. The oocytes are smaller; the reduction in membrane
      area, and therefore capacitance, leads to a faster settling time during a voltage
      clamp step. In addition, there appears to be less Ca(2+)-activated chloride
      current; this may render the stage II-III oocyte a useful system for studying K+
      channels, where chloride currents can be a significant problem. Conversely,
      though, these early stage oocytes may not be useful for expression of
      neurotransmitter receptors coupled to phospholipase C, for such receptors are
      often monitored by activation of the Cl-current. The injections of RNA are
      technically more difficult in stage II-III oocytes. This can, however, be
      overcome with some simple modifications of the injection apparatus, mainly
      inclusion of a pump or similar device for actual injections.

PMID- 1382190
TI  - Intracellular perfusion of Xenopus oocytes.

PMID- 1382191
TI  - Recording of gating currents from Xenopus oocytes and gating noise analysis.

PMID- 1382192
TI  - Ligand-binding assays in Xenopus oocytes.

PMID- 1382193
TI  - Expression of gap junctional proteins in Xenopus oocyte pairs.

PMID- 1382194
TI  - Vaccinia virus as vector to express ion channel genes.

PMID- 1382195
TI  - Probing molecular structure and structural changes of voltage-gated channel by
      expressing mutant channels in yeast and reconstituting them into planar
      membranes.

PMID- 1382196
TI  - Insertion of ion channels into planar lipid bilayers by vesicle fusion.

PMID- 1382197
TI  - Planar lipid bilayers on patch pipettes: bilayer formation and ion channel
      incorporation.

PMID- 1382198
TI  - Surface charge effects on ion conduction in ion channels.

PMID- 1382199
TI  - Determination of ion permeability by fluorescence quenching.

PMID- 1382200
TI  - Synthetic peptides and proteins as models for pore-forming structure of channel
      proteins.

PMID- 1382202
TI  - Isolation of ion channel genes by expression cloning in Xenopus oocytes.

PMID- 1382201
TI  - Purification and reconstitution of skeletal muscle calcium channels.

PMID- 1382203
TI  - Hybrid arrest technique to test for functional roles of cloned cDNAs and to
      identify homologies among ion channel genes.

PMID- 1382204
TI  - Cloning of ion channel gene families using the polymerase chain reaction.

PMID- 1382205
TI  - Overview of toxins and drugs as tools to study excitable membrane ion channels:
      II. Transmitter-activated channels.

PMID- 1382206
TI  - Patch clamp techniques to study ion channels from organelles.

PMID- 1382207
TI  - Patch clamp studies of microbial ion channels.

PMID- 1382208
TI  - Studies on intact sarcoplasmic reticulum: patch clamp recording and tension
      measurement in lobster split muscle fibers.

PMID- 1382209
TI  - Software for acquisition and analysis of ion channel data: choices, tasks, and
      strategies.

PMID- 1382210
TI  - Ion channels. Single-channel analysis.

PMID- 1382211
TI  - Ion channels. Analysis of nonstationary single-channel currents.

PMID- 1382212
TI  - Ion channels. Preventing artifacts and reducing errors in single-channel
      analysis.
AB  - The power of single-channel analysis techniques has rapidly expanded during the
      past few years, giving investigators increased ability to identify models and
      estimate parameters while reducing error and artifacts. At present, however,
      there is no single best method, as even the most advanced techniques have various
      limitations which depend on the experimental data and models being examined.
      Consequently, for the examined models and experimental data, the most critical
      part of single-channel analysis is to estimate errors and evaluate the ability of
      the methods used to discriminate among possible gating mechanisms. The magnitudes
      of the errors and the ability to identify models and estimate parameters depend
      on the models being examined as well as the experimental conditions and data.
      Consequently, the evaluation of the errors associated with each method needs to
      be repeated when the experimental data and examined models change.

PMID- 1382214
TI  - Calculation of ion currents from energy profiles and energy profiles from ion
      currents in multibarrier, multisite, multioccupancy channel model.

PMID- 1382213
TI  - Analysis of drug action at single-channel level.
AB  - Many drugs interact directly with ion channel proteins to alter gating and
      permeation functions. Single-channel recording affords resolution of drug-induced
      functional changes in channel behavior at the molecular level. Drug and toxin
      molecules that block ion channels are useful probes of channel mechanisms because
      blocking sites are often coupled to other pharmacologically relevant binding
      sites. Simple kinetic schemes describing fast block, slow block, and binding
      competition between two blocking molecules provide useful models of drug-induced
      blocking processes. From a careful perspective, a single channel is best
      approached as the analog of a purified enzyme preparation in the hands of an
      enzymologist. The confidence gained by knowing that one is viewing a single
      subtype must be weighed against the possibility that the channel could have been
      altered in the process of patch isolation or bilayer reconstitution. As in all
      kinetic studies, a curve fit to a two-state scheme is contingent on the
      possibility that a more complex multi-state system can masquerade as the simple
      cartoon one would like to put forward.

PMID- 1382215
TI  - Ion channel selectivity, permeation, and block.

PMID- 1382216
TI  - [Prevalence of hepatitis C virus antibodies in hospital personnel].
AB  - In this study, 416 hospital staffs from different departments and profession were
      screened for Hepatitis C virus (HCV) antibody by Enzyme Immune Assay method. Two
      hundred fifty blood bank donors were tested as a control group. Anti HCV
      positivity were found in four of hospital staffs (0.9%) and in four of donors
      (1.6%). According to our results, generally we didn't find any data about
      transmission of hepatitis C virus from hospital but it is interesting that all of
      the positive cases were from intensive care units.

PMID- 1382217
TI  - [An epidemiological study of the health conditions of Milan traffic police with
      respect to pollution from vehicular traffic].
AB  - An investigation on the health effects of occupational exposure to motor vehicle
      exhaust and environmental pollutants was carried out on traffic wardens in Milan
      (Italy). Randomized samples of 292 traffic wardens (exposed group) and 60
      hospital staff members (control group) underwent a physical examination and
      laboratory tests. No significant difference was observed between the exposed and
      control groups as regards general morbidity, apart from musculo-skeletal
      disorders in females. The mean blood lead level (PbB) among traffic wardens was
      15.2 micrograms/dl compared with 11.7 in control (p less than 0.01). The
      carboxyhaemoglobin concentration (COHb) in traffic wardens at the beginning of
      the shift was 2.8% for smokers and 1.2% for non-smokers (3.0% and 0.9%
      respectively in controls). At the end of the shift COHb in the exposed group was
      4.3% for smokers and 2.5% for non-smokers (p less than 0.01). PbB was
      significantly correlated (r = 0.17) with Median Nerve Motor Conduction Velocity
      (NCV) in the exposed but not in the control group. The same pattern was observed
      for the correlation of PbB and Systolic Blood Pressure (SBP) (r = -0.24). COHb
      was significantly correlated with HDL cholesterol (r = -0.20) in the exposed
      group only. It is questionable whether very low PbB levels can affect NCV and SBP
      directly or rather whether PbB, as well as COHb, should be regarded as tracers of
      exposure to those urban pollutants leading also to cardiovascular and nervous
      disorders.

PMID- 1382218
TI  - Characterization of the 5'-flanking transcriptional regulatory region of the
      human Fc gamma receptor gene, Fc gamma RIIA.
AB  - The human Fc gamma receptor gene Fc gamma RIIA is expressed in platelets,
      neutrophils, monocytes and macrophages. Understanding the regulation of
      expression of Fc gamma RIIA will enhance our knowledge of regulated gene
      expression and immune function in these cells. We cloned a 3.65 kb region of the
      5' end of the Fc gamma RIIA gene and characterized 3.4 kb of previously
      unreported sequence of the 5'-flanking region. Primer extension studies and RNase
      protection analyses of mRNA from HEL, K562 and U937 cells revealed multiple
      transcription start sites. One transcription start site mapped to a 5'
      untranslated (5'UT) exon approximately 1 kb 5' to the ATG translation initiation
      codon, while a second start site mapped near the ATG codon. Reverse transcription
      combined with PCR (RT-PCR) employing an oligonucleotide in the putative 5'UT exon
      and an antisense oligonucleotide in the translated region yielded products which
      confirm that transcription starts in this 5'UT exon 881 bp upstream of the ATG
      codon. Sequence analysis of the RT-PCR products showed two related RNA splice
      products which use alternative 3'-consensus AG splice acceptor sites. Fc gamma
      RIIA mRNA thus has three distinct potential 5'UT regions, two alternatively
      spliced forms from the start site in the 5'UT exon and the third from the start
      site near the ATG codon. Comparisons of the human Fc gamma RIIA 5'-flanking
      region with human Fc gamma RI and mouse Fc gamma RII beta genes as well as with
      other genes expressed in megakaryocytes, neutrophils and monocytes reveal
      structural similarities and shared promoter elements.

PMID- 1382219
TI  - Subtyping of human immunodeficiency virus isolates with a panel of monoclonal
      antibodies: identification of conserved and divergent epitopes on p17 and p25
      core proteins.
AB  - We have investigated the feasibility and significance of subtyping of human
      immunodeficiency virus (HIV) isolates with monoclonal antibodies (mAb) raised
      against the core proteins of HIV. A panel of 37 mAb tested for reactivity with
      HIV1 oligopeptides was used to analyse the antigenic relatedness among 14 HIV
      isolates which included 12 isolates of HIV1 from different geographical origins
      and 2 isolates of HIV2. Three out of these 37 mAb reacted with conserved epitopes
      expressed by all 14 HIV isolates tested. These reagents which included 2 mAb
      reacting with the 285-310 amino acid sequence of p25 and 1 mAb reacting with an
      epitope of p25 not mapped by the peptides' approach, also reacted with a non
      human primate lentivirus. Five mAb reacting either with the 11-25 or 121-132
      amino acid sequences of p17 or the 302-320 amino acid sequence of p25 reacted
      with strain-specific epitopes. The other 29 mAb reacted with polymorphic epitopes
      and thereby define subfamily and subtype-specific markers.

PMID- 1382220
TI  - Epitope analysis of the allergen ovalbumin (Gal d II) with monoclonal antibodies
      and patients' IgE.
AB  - Ovalbumin (OVA) is a major allergen (Gal d II) of hen egg white and is often the
      cause of hypersensitivity reactions to food. Further knowledge of the antigenic
      and allergenic epitopes of allergens will provide better treatment of this
      disease. To analyse these epitopes we produced a panel of monoclonal antibodies
      (mAbs) against native OVA. The initial information about the epitopes was
      obtained with the binding patterns of these mAbs in IEF-immunoprints and western
      blots of OVA under reducing and non-reducing conditions. It was possible to
      demonstrate that the different conformations of OVA exhibit different epitopes,
      and that there are other epitopes which are shared by each conformation. Seven
      different, although sometimes overlapping epitopes, could be determined on native
      OVA; four different epitopes on denaturated non-reduced OVA by means of
      immunoblots of the intact molecule. The number of epitopes which could be
      differentiated by the mAbs was increased by the use of peptide blots after CNBr
      fragmentation of the molecule. IgE binding to different OVA conformations and to
      CNBr-fragments of OVA was also detectable and appears in the same regions as the
      reactivity of some mAbs. Western blots of OVA and CNBr-peptides demonstrate that
      some antigenic/allergenic binding sites seem at least partly to be continuous
      epitopes. The identification of the CNBr-fragments was performed by a
      microsequence analysis of blotted CNBr-fragments after a 2-dimensional
      electrophoresis. IgE was found to bind the two largest CNBr-fragments (residues
      41-172 and 301-385), but not the fragment corresponding to residues 173-196. A
      number of monoclonal antibodies also reacted with the two large fragments,
      especially with fragment 301-385, and some bind also to shorter peptides, such as
      fragment 173-196, which were not reactive to patients' IgE. Most of the
      monoclonal antibodies and patients' IgE bind to the fragments 41-172 and 301-385
      in 2D-PAGE blots suggesting that these fragments are involved in an immunogenic
      structure.

PMID- 1382221
TI  - DNA probes for Bordetella species and a colorimetric reverse hybridization assay
      for the detection of Bordetella pertussis.
AB  - Three oligonucleotide probe sequences were inferred from the 16S ribosomal
      ribonucleic acid (rRNA) and the 16S-23S rRNA spacer sequences of Bordetella
      pertussis ATCC 10380. These probes were used in hybridization tests with
      deoxyribonucleic acid from Bordetella species and other relevant bacterial taxa.
      A probe from the spacer region hybridized exclusively to the B. pertussis strains
      tested and not to strains from other species. Using a combination of three
      probes, B. pertussis, B. parapertussis/B. bronchiseptica and B. avium could be
      specifically identified and differentiated from other taxa. Differentiation
      between B. parapertussis and B. bronchiseptica was not possible with the probes
      used. Using the spacer probe, a colorimetric hybridization assay specific for B.
      pertussis was developed based on enzymatic amplification of the 16S-23S rRNA
      spacer and reverse hybridization in microtitre wells. As compared with results
      using agarose gel electrophoresis, and Southern and dot-spot hybridization with a
      32P-labelled probe, this assay proved to be faster and easier to perform and was
      found to be at least as sensitive and specific.

PMID- 1382222
TI  - Fluorescence-based, multiplex allele-specific PCR (MASPCR) detection of the delta
      F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR)
      gene.
AB  - Cystic fibrosis (CF) is a common genetic disorder in Caucasians, and in some
      populations 70% of cases are associated with a 3 base pair (bp) deletion (delta
      F508) in the CFTR gene. We have implemented a fluorescence-based, multiplex
      allele-specific polymerase chain reaction (MASPCR) assay for deletion of the
      delta F508 mutation. Different allele-specific fluorescently-tagged primers are
      used in the PCR reaction to distinguish between normal and delta F508 alleles.
      Fluorescent PCR products are then visualized in a single lane on an agarose gel
      following electrophoresis combined with real-time multicolour fluorescence
      detection. The approach simplifies diagnosis of the most common mutation in the
      CFTR gene, and holds promise for a multiplex allele-specific, fluorescence-tagged
      gene amplification strategy for detection of additional CF mutations which may
      result in more cost-effective testing without increasing the risk of missed or
      erroneous diagnoses.

PMID- 1382223
TI  - Structure-mutagenicity relationships in a series of indolo[3,2-c]quinoline-1,4
      diones that have shown cytotoxic properties on leukemia cells.
AB  - A series of seven 6-methylindolo[3,2-c]quinoline-1,4-diones substituted either in
      the 2 position or in 3 position by various groups were examined for their ability
      to induce mutation in the Ames test at several concentrations in four strains of
      Salmonella typhimurium (TA97, TA98, TA100, and TA102). First, relationships were
      established between their mutagenic activities and either the nature or the
      position of the substituent on the quinonic nucleus. Compounds substituted in the
      2 position were less mutagenic than the 3 isomers. In the second study, the
      mutagenic properties were compared to the in vitro antitumor activity.
      Interestingly, some very cytotoxic quinones were only weak mutagens. So where the
      cytotoxicity is similar, the less mutagenic compounds may be suitable for
      clinical use as antitumor drugs, in order to avoid important side effects; the
      Ames test can then be used guide the selection of molecules for further in vivo
      antitumor screening. It can also be very helpful in selecting the best candidate
      molecules to be synthesized.

PMID- 1382224
TI  - Mutagenic activities of azido analogues of amsacrine and other 9-anilinoacridines
      in Salmonella typhimurium and their enhancement by photoirradiation.
AB  - Analogues of amsacrine and other 9-anilinoacridines, bearing azide groups at
      various positions, were tested for their mutagenic activity in five strains of
      Salmonella typhimurium, both before and after photoirradiation. Azido
      substitution at the 2- or 3-position of the acridine or the 1'-position of the
      aniline led to compounds which were active frameshift mutagens, as detected in
      strain TA1537. Photoirradiation enhanced both the mutagenicity and the
      cytotoxicity of the azido compounds. Analogues bearing two azido groups at either
      the 2,6- or 3,6-positions were less strongly mutagenic in the dark, and light
      activation led to a toxic but only weakly mutagenic product. The effects of
      photoirradiation were decreased by aniline ring substitution, and were
      essentially eliminated by additional methyl substitution in the acridine ring.
      Comparison of events in TA1537 and TA98 suggested that photoirradiation of the 2-
      or 3-azido compounds gave a product which was capable of forming covalent bonds
      with DNA. The azide-containing analogues readily formed single strand DNA breaks
      on irradiation in the presence of DNA, but the efficiency of this reaction varied
      considerably.

PMID- 1382225
TI  - 1,4-Dioxane: prediction of in vivo clastogenicity.
AB  - 1,4-Dioxane was analyzed with the CASE program to determine the structural basis
      of its potential genotoxicity and carcinogenicity. These investigations led to
      the prediction that while 1,4-dioxane was not genotoxic in vitro, it was an
      inducer of micronuclei in the bone marrow of rats and a carcinogen for both rats
      and mice. If it is assumed that the induction of micronuclei is the result of DNA
      damage, then this potential and the previous report of the in vivo induction of
      DNA strand breaks in rat liver raise the possibility of a genotoxic action for
      1,4-dioxane. However it is also conceivable that we have identified a structural
      feature which contributes to the induction of micronuclei by a non-genotoxic
      mechanism.

PMID- 1382226
TI  - A cytogenetic study of men environmentally and occupationally exposed to airborne
      pollutants.
AB  - The level of sister-chromatid exchanges (SCE), high-frequency cells (HFC),
      chromosomal aberrations (CA) as well as the proliferation rate index (PRI) were
      measured in peripheral blood lymphocytes from three groups of volunteers. The
      environmentally exposed donors were residents from the vicinity of a coke
      factory; the occupationally exposed persons were cokery workers, while rural
      region inhabitants served as a control group. Compared with the control group,
      statistically significant increases of SCE and HFC, as well as decreased cell
      kinetics (PRI) were observed for both occupationally and environmentally exposed
      groups. The effect was especially pronounced when only smokers were taken into
      account. A statistically significant increase of CA was observed in the
      environmentally exposed group when CA including gaps (CA + G) were evaluated. The
      proportion of HFC was found to be the most sensitive method to detect genetic
      effects on the tested human population. This study demonstrates the usefulness of
      all 4 biomarkers (SCE, HFC, CA and PRI) in monitoring populations exposed to
      ambient pollution and clearly indicates effects from residential as well as
      occupational exposure to industrial air pollutants.

PMID- 1382227
TI  - Cytogenetics study on coke oven workers with abnormal blood counts.
AB  - Thirty steelworkers with abnormal blood counts and 22 controls were studied
      cytogenetically. Fifty percent of the workers had a combination of leukopenia,
      neutropenia and lymphocytosis, and the remaining 50% showed different
      combinations or even a single type of alteration. The frequency of chromosome and
      chromatid gaps and chromosome deletions was significantly higher among workers
      than among controls, and the same was true for the number of individuals with
      some type of chromosome alteration. We also noted that the major factor related
      to the production of chromosome breaks is not the total time of work in the steel
      mill, but specifically the time of work at the coke oven.

PMID- 1382228
TI  - Cytogenetic study in peripheral blood lymphocytes from asthmatic patients
      receiving continued therapy with theophylline.
AB  - Possible cytogenetic effects of theophylline have been investigated in asthmatic
      patients undergoing continuous therapy with this drug. Sister-chromatid exchanges
      (SCE), chromosome aberrations (CA) and proliferating rate indices (PRI) were
      evaluated in cultured peripheral blood lymphocytes from patients receiving
      theophylline alone, theophylline plus inhaled beta 2 adrenergic drugs or
      theophylline in combination with beta 2 adrenergic agents and corticoids. Two
      samples from each individual were obtained in order to perform a prospective
      study: before the theophylline medication (sample A) and at a time after the
      beginning of treatment (sample B). After treatment (66.3 +/- 37.8 days), an
      increase in SCE was observed without modifications either in PRI or in CA.
      Patients receiving beta 2 adrenergics or beta 2 adrenergics plus glucocorticoids
      before and during theophylline treatment, did not respond differently than those
      on theophylline alone.

PMID- 1382229
TI  - Effects of amino acids on sister-chromatid exchanges.
AB  - The effects of 10 amino acids on sister-chromatid exchange (SCE) frequency in
      human peripheral blood lymphocytes (PBL) and six amino acids on the SCE frequency
      in root tip cells of Hordeum vulgare were studied. Alanine (Ala), glycine (Gly),
      phenylalanine (Phe), valine (Val), histidine (His) and serine (Ser) induced a
      significant increase in SCE in PBL but threonine (Thr), isoleucine (Ile), lysine
      (Lys) and arginine (Arg) did not. Ala, Gly, Thr, Ile and Val induced a
      significant increase in SCE in root tip cells of Hordeum vulgare but Lys did not.
      The effect of Lys and bromodeoxyuridine (BrdU) on SCE levels in PBL and the
      interaction between them were also studied. The results show that Lys can inhibit
      the SCE induced by BrdU.

PMID- 1382230
TI  - Cytogenetic studies on gas station attendants.
AB  - Forty-nine gas station attendants employed to pump fuel and 24 controls were
      studied cytogenetically. This type of worker is occupationally exposed to fuel
      fumes and to automotive vehicle emissions. Chromosome analysis showed a
      significantly higher frequency of chromosome deletions among the gas station
      attendants than a control group. Taking into account the relationship between
      clastogenicity and increased cancer risk, we may consider these workers to form a
      risk group.

PMID- 1382231
TI  - Genotoxicity of four herbicides in the Drosophila wing spot test.
AB  - The herbicides alachlor, atrazine, maleic hydrazide and paraquat were evaluated
      for genotoxicity in the Drosophila melanogaster wing spot test. Third-instar
      larvae trans-heterozygous for two recessive mutations of wing trichomes, multiple
      wing hairs (mwh) and flare (flr3), were treated by chronic feeding with different
      concentrations of the four herbicides. Feeding ended with pupation of the
      surviving larvae. The genotoxic effects were determined from the appearance of
      clones of cells with mwh, flr3 or mwh-flr3 phenotypes. Exposure to maleic
      hydrazide resulted in a significant increase in the frequency of the three
      categories of spots recorded (small single, large single and twin spots) in a
      dose-related fashion. Exposure to alachlor induced significant increases in both
      small and total spots at the four concentrations assayed and in the frequency of
      twin spots at the highest concentration tested (10 mM). Atrazine and paraquat
      also induced significant increases in both small and total spots at three of the
      four concentrations tested, without indication of a direct dose-effect
      relationship.

PMID- 1382232
TI  - Cystic fibrosis in the mouse by targeted insertional mutagenesis.
AB  - Cystic fibrosis is a fatal genetic disorder which afflicts 50,000 people
      worldwide. A viable animal model would be invaluable for investigating and
      combating this disease. The mouse cystic fibrosis transmembrane conductance
      regulator gene was disrupted in embryonal stem cells using an insertional gene
      targeting vector. Germ-line chimaeras were derived and the offspring of
      heterozygous crosses studied. These homozygous mutant mice survive beyond
      weaning. In vivo electrophysiology demonstrates the predicted defect in chloride
      ion transport in these mice and can distinguish between each genotype.
      Histological analysis detects important hallmarks of human disease pathology,
      including abnormalities of the colon, lung and vas deferens. This insertional
      mouse mutation provides a valid model system for the development and testing of
      therapies for cystic fibrosis patients.

PMID- 1382233
TI  - Synthesis of nucleic acids in blood cells in mice after irradiation with gamma
      rays.
AB  - In the blood of mice irradiated with a single total-body dose of 8 Gy gamma rays
      we examined the concentration of nucleic acids and incorporation of 3H-thymidine
      and 14C-orotic acid. The concentration of nucleic acids, above all that of DNA in
      the so-called blood leukocyte mass dropped significantly in the course of the
      first three days after irradiation. Recovery began in the course of the second
      week following irradiation. On day 21 after irradiation, DNA concentration was
      found to be recovered temporarily and RNA concentration to exceed the control
      values. The increase of incorporation of 3H-thymidine confirmed an increased
      incidence of DNA synthesizing cells in the blood within days 12-15 after
      irradiation. Since the increase of incorporation of 3H-thymidine into DNA was not
      preceded by an increase of incorporation of 14C-orotic acid into RNA, we presume
      that the DNA synthesizing cells in the blood of irradiated animals do not
      represent the stimulated lymphocytes but circulating hemopoietic cells.
      Therefore, the examination of DNA synthesis in blood cells enables to record the
      course of bone marrow regeneration after irradiation or after application of
      hemopoiesis depressing substances.

PMID- 1382234
TI  - Intensive combination chemotherapy (TTL-I protocol) of large cell and
      immunoblastic lymphomas--long-term observation.
AB  - Fifty patients with advanced (Stage III and IV) large cell and immunoblastic
      lymphoma were treated with eight 4-week courses of chemotherapy. The first two
      identical A courses were composed of high dose cyclophosphamide, vincristine, 5
      day administration of bleomycin, 2-week prednisone, and methotrexate with calcium
      leucovorin. The next two "B" courses were composed of vincristine, 3-day
      administration of doxorubicin together with bleomycin, and prednisone. The next
      two "C" courses were composed of cyclophosphamide, vincristine, bleomycin,
      prednisone, methotrexate, and calcium leucovorin. The last two "D" courses were
      the same as "B" courses. CNS prophylaxis was done with intrathecal methotrexate.
      Fourty-two patients (84%) achieved complete remission, 7 patients entered partial
      remission, and 1 patient failed to respond. The median survival of all groups was
      80 + months (range 2-181 + months). Nine patients relapsed (21%), and seven
      patients died in complete remission, three of them died of toxicity. The most
      frequent toxicity was myelosuppression, mostly leukopenia, frequently followed by
      infection, sometimes severe. Neurotoxicity and stomatitis were frequent, but
      usually not severe. Two patients developed secondary malignancies. Most of the
      patients (54%) are alive without evidence of disease at present.

PMID- 1382235
TI  - Quality control program of steroid receptor assays: an international study.
AB  - Lyophilized calf uterine cytosol standards were prepared for quality control of
      estrogen receptor (ER) determination, and lyophilized cytosols and tissue powders
      were used for quality control of progesterone receptor (PR) analysis. Two series
      of four samples were analyzed either for ER or PR contents, twice within one
      month, by 7 laboratories in 5 countries. Coefficient of variation (CV) of the
      between-laboratory averages assayed in a single run of ER-positive (ER+) and PR
      positive (PR+) standards varied from 29.6 to 61.8% and from 32.4 to 76.2%,
      respectively. All laboratories, with the exception of a single value, could
      recognize samples of low, medium, an high ER level, as well as a negative sample.
      Most laboratories evaluated properly also the level of PR samples. The average
      between-laboratory CV values of protein determination in the relevant standards
      were 23%.

PMID- 1382236
TI  - Renal involvement in sickle cell-beta thalassemia.
AB  - Renal function studies were performed in 41 patients with sickle cell-beta
      thalassaemia (S/b thal) and compared to 14 normal controls and 8 sickle cell (SS)
      patients. Polyuria, hyposthenuria and mild proteinuria were common in both S/b
      thal and SS patients. A renal concentrating defect was manifest in all patients
      studied, and in 4 of the 7 S/b that patients tested, an abnormal acidification
      test was found. A statistically significant negative correlation (n = 19, r = 
      0.48, p less than 0.05) was noted between creatinine clearance (CCr) and age for
      the patients over 30 years. There was no correlation between hemoglobin and CCr;
      on the contrary, a statistically significant negative correlation was found
      between CCr and hemoglobin F (n = 29, r = -0.428, p less than 0.05) Our S/b thal
      and SS patients showed a decreased daily excretion of sodium, calcium, phosphate
      and magnesium and lower serum magnesium levels than the controls. One third of
      the S/b thal patients showed hyperuricosuria, and a statistically significant
      negative correlation was noted between serum uric acid and its fractional
      excretion in all S/b thal patients (n = 41, r = -0.450, p less than 0.01). Serum
      phosphate levels were independent of age. A statistically significant positive
      correlation was found between the tubular reabsorptive capacity for phosphate and
      the number of painful crises per year (n = 33, r = 0.836, p less than 0.001). We
      conclude that renal involvement in the double heterozygous state is as severe as
      in homozygous sickle cell disease.

PMID- 1382237
TI  - Hepatitis C virus infection and hepatic function in chronic hemodialysis
      patients.

PMID- 1382238
TI  - HES as an osmotic agent for continuous ambulatory peritoneal dialysis solutions.

PMID- 1382240
TI  - Comparative immunohistochemical study on the expression of alpha B crystallin,
      ubiquitin and stress-response protein 27 in ballooned neurons in various
      disorders.
AB  - This report deals with a comparative study on the expression of alpha B
      crystallin, ubiquitin, stress-response protein 27 (srp 27), srp 72 and
      phosphorylated neurofilament protein (pNFP) by ballooned neurons in Pick's
      disease, Creutzfeldt-Jakob disease (CJD), amyotrophic lateral sclerosis (ALS),
      leptomeningeal carcinomatosis, anterior spinal artery syndrome and pellagra.
      Immunohistochemical techniques were used. alpha B Crystallin was expressed by the
      majority of ballooned neurons of Pick's disease and CJD, but not by those of the
      other disorders. Ubiquitin and srp 27 expression was also restricted to abnormal
      neurons of Pick's disease and CJD, but the proportion of stained cells was less
      than that expressing alpha B-crystallin. There was no evidence of ballooned
      neurons expressing srp 72. Except for those of pellagra patients, phosphorylated
      neurofilament protein (pNFP) was detected in most abnormal neurons. Our results
      suggest that the mechanisms involved in formation and maintenance of swollen
      neurons in Pick's disease and CJD may be different than those of ballooned
      neurons in the other entities studied.

PMID- 1382239
TI  - Some regional anatomical relationships of TRH to 5-HT in rat limbic forebrain.
AB  - It is now a recognized principle that various neuropeptides are neuronally co
      localized with biogenic amine or aminoacid neurotransmitters. In the rat CNS it
      has previously been shown that TRH is co-localized with 5-HT (and also with
      substance P) in cell bodies of the posterior raphe that project to the spinal
      cord. Although TRH cell bodies are known to be widely distributed throughout the
      forebrain there is no other known co-localization with 5-HT. In this study we
      further specify the forebrain there is no other known co-localization with 5-HT.
      In this study we further specify the anatomical relationship of TRH with 5-HT by
      use of surgical and neurotoxic lesioning with reference to limbic forebrain
      regions wherein TRH is greatly increased following seizures. In groups of rats,
      the fimbria-fornix was lesioned alone, or combined with a lesion of the dorsal
      perforant path or the ventral perforant path. There was a sham lesioned control
      group. Additional groups were lesioned with 5,7 dihydroxytryptamine, 100
      micrograms i.v.t., 45 min. after i.p. desipramine, 25 mg/kg. All rats were
      sacrificed three weeks after lesions. Indoleamines were determined by HPLC in
      left anterior cortex, left pyriform/olfactory cortex, left dorsal hippocampus and
      left ventral hippocampus. TRH was determined by specific RIA in the corresponding
      right brain regions. The modal n was 7 rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382241
TI  - Ubiquitin, PGP 9.5 and dense body formation in trimethyltin intoxication:
      differential neuronal responses to chemically induced cell damage.
AB  - Ubiquitin in normal cells may be important in degrading or transferring short
      lived or aberrant proteins to lysosomal dense bodies. To examine its role in
      degrading proteins produced by a chemical insult, changes in the distribution of
      ubiquitin and the carboxy-terminal hydrolase, PGP 9.5, have been studied in rat
      hippocampal neurons and cerebellar Purkinje cells in trimethyltin intoxication.
      Here tubulovesicular dense bodies (TVBs) form from 12h onwards associated with
      vacuolation of the Golgi apparatus. Striking accumulations of lysosomal dense
      bodies follow in hippocampal pyramidal cells but not in cerebellar Purkinje
      cells; many of the hippocampal neurons later die, while the Purkinje cells
      generally survive. Ubiquitin immunoreactivity was diffusely increased in
      hippocampal pyramidal and Purkinje cells 6 h after dosing. By 12 h both diffuse
      and granular ubiquitin immunoreactivity was present that intensified over 24 and
      48 h. Both by light and electron microscopy TVBs showed ubiquitin
      immunoreactivity, but dense bodies in hippocampal perikarya did not stain with an
      anti-ubiquitin antibody. PGP 9.5 immunoreactivity was not altered in hippocampal
      cells at any time, while Purkinje and Golgi cell dendrites and perikarya showed
      intensified labelling at 3 h that reached a peak of 12 h. At 48 h Western blot
      analysis of hippocampal homogenates showed significant increases in high
      molecular weight (HMW) ubiquitin conjugates, while cerebellar homogenates showed
      an increase in ubiquitin-histone conjugates. Northern blot analyses showed no
      change in ubiquitin or PGP9.5 gene expression in hippocampus or cerebellum. These
      findings suggest that the material in the TVBs in hippocampal cells is not being
      degraded by the ubiquitin system but passes ubiquitinated into the lysosomal
      system, while material in Purkinje cell TVBs is degraded by the ubiquitin system,
      suggesting it may have a different composition in each type of neuron.

PMID- 1382242
TI  - Experimental traction injuries of cervical spinal nerve roots: a scanning EM
      study of rupture patterns in fresh tissue.
AB  - This study examines the levels at which fresh rat ventral and dorsal C4 to T1
      spinal roots rupture under traction stress. Rupture rarely occurs at the CNS-PNS
      transitional zone. Despite its delicate appearance this is strengthened in a
      number of ways, so that it is less vulnerable than the roots and their
      constituent rootlets and aggregated rootlet bundles (ARBs). Ventral roots
      commonly rupture either where the rootlets join to form the ARBs, along the
      course of the latter, or where these in turn join to form the ventral root.
      Dorsal root rupture shows a similar pattern but has a higher frequency of rupture
      within the root proper than is the case with the ventral roots. The level of
      rupture also varies systematically over the series of roots examined: rupture
      points tend to be located at more distal levels in caudal roots. This may occur
      because of mechanical differences in the distribution of traction stress along
      roots, related to their courses through the vertebral canal. Upper roots run
      transversely and the traction force is transmitted directly to rootlet levels,
      while more caudal roots run obliquely and tend to rupture where they are drawn
      taut against the pedicle. Many of the morphological features of ruptured roots
      would tend to inhibit regeneration of fibres distally. Differences in the pattern
      of rupture between fresh and fixed roots are examined. The latter tend to rupture
      at levels closer to the CNS than the former.

PMID- 1382243
TI  - The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat
      and mouse--1. Rubidium.
AB  - The administration of TCP (15 mg/kg, i.p.) to rats pretreated with either
      intraperitoneal RbCl (3 mmol/kg, twice daily for 5 days) or dietary RbCl (30
      mmol/kg diet, for 14 days), resulted in the complete 5-HT behavioural syndrome.
      Pretreatment with p-chlorophenylalanine (i.p. 300 mg/kg x2) or (-)-propranolol
      (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg, s.c.)
      prevented the occurrence of the 5-HT syndrome, produced by dietary RbCl plus TCP.
      Intraperitoneal administration of RbCl had no effect upon the 5-HT behavioural
      syndrome, produced by 8-OH-DPAT (0.5 mg/kg, s.c.) or 5-MeODMT (2 mg/kg, i.p.) but
      enhanced the 5-HT syndrome produced by quipazine (20 mg/kg, i.p.), DOI (8 mg/kg,
      s.c.), p-chloramphetamine (4 mg/kg, i.p.) or by TCP plus L-tryptophan (50 mg/kg,
      i.p.) in rats. Dietary administration of RbCl resulted in the enhancement of the
      5-HT2-mediated head-twitches in the mouse and the attenuation of hypothermia in
      the mouse, induced by 8-OH-DPAT (0.5 mg/kg, s.c.). The accumulation of 5-HT
      (after inhibition of monoamine oxidase) and the rate of synthesis of 5-HT in the
      whole brain (minus cerebellum) were enhanced by dietary and intraperitoneal
      administration of RbCl, respectively. The effects of lithium and rubidium,
      respectively, on 5HT function in brain are compared.

PMID- 1382244
TI  - 5-HT3 receptors are not involved in the modulation of the K(+)-evoked release of
      [3H]5-HT from spinal cord synaptosomes of rat.
AB  - The ability of 5-HT3 receptor agonists to modulate the resting efflux or K(+)
      evoked release of [3H]5-HT from superfused synaptosomes from the spinal cord of
      the rat was investigated. Phenylbiguanide did not alter the resting efflux of
      [3H]5-HIAA or [3H]5-HT or modify the K(+)-evoked release of [3H]5-HT. 2-Methyl-5
      HT (10 microM) caused an increase in resting efflux of [3H]5-HIAA, an effect that
      was blocked by the inhibitor of the uptake of 5-HT fluoxetine. No effect on K(+)
      evoked release of tritium was observed. Bufotenine (100-1000 nM) increased the
      resting efflux of [3H]5-HT and [3H]5-HIAA. These effects were not antagonized by
      the 5-HT3 antagonist ICS 205-930 but were antagonized by fluoxetine. The drug ICS
      205-930 (1 microM) did not alter resting efflux or block the ability of serotonin
      (30 and 100 nM) to decrease K(+)-evoked release of tritium. Quipazine, a potent
      antagonist of peripheral 5-HT3 receptors (subnanomolar concentrations), was also
      unable to alter resting or K(+)-evoked release of [3H]5-HT. It did, however,
      attenuate the inhibitory effect 5-HT on K(+)-evoked release. The concentrations
      required were in the micromolar range, consistent with the ability of the drug to
      antagonize the 5-HT1B autoreceptor. These results support the idea that 5-HT3
      receptors do not act as nerve terminal autoreceptors in the spinal cord of the
      rat.

PMID- 1382245
TI  - Behavioural consequences following infusion of selective neurokinin agonists into
      the median raphe nucleus of the rat.
AB  - The locomotor activity induced after infusion of selective neurokinin (NK)
      agonists into the median raphe nucleus of rats was investigated. In photocell
      cages, the NK-2-agonist, GR64349, and the NK-3 agonist, senktide, both increased
      motor activity in a dose-dependent manner. However, the NK-1 agonist, GR73632,
      had little effect over a range of doses. In the open field, the motor effect of
      all three NK agonists was identical to that observed in the photocell cages. In
      addition, senktide induced straub-tail, hind-limb splaying and various oral
      movements. Such effects were not noted with the other two agonists. These results
      suggest that activation of NK-2 or NK-3 receptors by the neurokinins, in the
      median raphe nucleus of the rat, leads to an increase in locomotor activity.

PMID- 1382246
TI  - Delta sleep-inducing peptide as a factor increasing the content of substance P in
      the hypothalamus and the resistance of rats to emotional stress.
AB  - The influence of delta sleep-inducing peptide (DSIP, 60 and 120 nmole/kg,
      intraperitoneally) on the content of substance P (SP) in the hypothalamus of rats
      was studied in male rats of the August line. It was demonstrated that the
      administration of DSIP significantly increases the average content of SP in the
      hypothalamus, as well as its content in animals resistant to and predisposed to
      emotional stress. A daily one-time administration of DSIP before placing the rats
      in conditions of stress increases the content of SP in the hypothalamus which was
      decreased during emotional stress. The preliminary one-time administration of
      DSIP to animals subjected to a stressor influence also increases the SP content
      in the hypothalamus. It was established that a one-time administration of DSIP in
      a dose of 60 nmole/kg sharply decreases the classical manifestations of stress
      such as the hypertrophy of the adrenals and involution of the thymus.

PMID- 1382248
TI  - The management of symptomatic benign prostatic hyperplasia with the once-daily
      alpha 1 blocker, terazosin.
AB  - The once-daily alpha 1 blocker terazosin was administered to 36 men with
      symptomatic benign prostatic hyperplasia (BPH) who had previously been scheduled
      for transurethral resection of the prostate (TURP). At 3 months, terazosin at 5
      mg q.d. produced improvements in symptom scores, peak urinary flow rates, mean
      urinary flow rates, and residual urine. These improvements were maintained at 6
      and 9 months. Terazosin also proved to be well tolerated, with no cases of
      hypotension or erectile dysfunction. We conclude that terazosin is effective in
      relieving obstructive urinary symptoms of BPH and that it allows many patients to
      be placed in a "holding pattern," allowing surgery to be delayed until the
      disease progresses. The use of terazosin also increased the capabilities of our
      urologic clinic. By reducing the urgency of surgery, it allowed us to schedule
      TURPs more conveniently and thereby accommodate more prostate surgery within the
      limited resources of our clinic. As a result, the use of terazosin saved
      considerable CHAMPUS dollars that would otherwise have been lost to the system.

PMID- 1382247
TI  - Influence of taurine on the electrically regulated ionic channels of the somatic
      membrane of neurons of the pond snail.
AB  - The influence of taurine (in concentrations of 10(-8) to 10(-2) mole/liter) on
      the fast sodium, calcium, and potassium, the slow potassium, and the leakage
      currents of the somatic membrane of the neurons of the pond snail was
      investigated. A monotonic decrease was demonstrated in the calcium and the slow
      potassium currents with an increase in the concentration of taurine. The sodium
      currents increased at taurine concentrations of 10(-8)-10(-4) mole/liter, while
      at concentrations of 10(-3)-10(-2) mole/liter they decreased. The fast potassium
      currents remained essentially unchanged at all concentrations of taurine. The
      leakage currents of the membrane at small concentrations of taurine decreased
      somewhat, and increased insignificantly at higher concentrations of it. All of
      the effects of taurine were reversible. It is hypothesized that the mechanism of
      the neuromodulatory, anticonvulsant, antihypoxic effects of taurine is at its
      base associated with changes in the electrically regulated ionic channels of the
      cell membrane.

PMID- 1382249
TI  - Inadequate prostate screening procedures.

PMID- 1382250
TI  - Unnecessary mastectomy for gynecomastia in testicular cancer patient.
AB  - A young man presented with a 4-month history of progressive, bilateral tender
      gynecomastia and underwent a bilateral subcutaneous mastectomy without regard for
      a possible occult testicular tumor. Following the mastectomy, metastatic
      testicular cancer was discovered; the patient had an overlooked scrotal mass and
      a very elevated serum human chorionic gonadotropin tumor marker. The possibility
      of testicular tumor must be considered in any male, especially those in the
      younger age group, who present with gynecomastia.

PMID- 1382252
TI  - Fast and slow depolarizations produced by substance P and other tachykinins in
      sympathetic neurons of rat prevertebral ganglia.
AB  - Using intracellular recording, we examined the effects of three mammalian
      tachykinins, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), on
      sympathetic neurons of isolated rat coeliac-superior mesenteric ganglia (C-SMG).
      The 3 tachykinins elicited two distinct depolarizing responses in ganglion cells:
      fast depolarization with time-to-peak of 1-2 sec and duration of 5-10 sec, and
      slow depolarization with time-to-peak of about 20 sec and duration of 120-140
      sec. Both fast and slow responses persisted in a solution containing low Ca2+ and
      high Mg2+ or tetrodotoxin, which indicates that the tachykinins directly act on
      ganglion cells to produce fast and slow depolarizations. The two types of
      tachykinin-induced responses exhibited clearly distinguishable properties. The
      membrane conductance was increased during the fast response, but not
      significantly changed, slightly decreased or sometimes increased during the slow
      response. Within certain range of membrane potential, the amplitude of fast
      response increased upon membrane hyperpolarization and decreased upon
      depolarization of ganglion cells. In contrast, the amplitude of slow response
      associated with membrane conductance decrease was increased with membrane
      depolarization and decreased with hyperpolarization. The fast response was
      markedly suppressed in a Na(+)-deficient solution, a solution containing
      nominally zero Ca2+ (plus 0.1 mM EGTA in some cases), and in a solution
      containing Cd2+ or Mn2+, whereas the slow response was not affected in these
      solutions and was augmented in some cells in K(+)-free solution. Thus it seems
      that the increase in Ca(2+)-dependent cationic conductance underlies the fast
      response and that the slow response is produced at least in part by suppression
      of certain K+ channels. The fast response progressively decreased in amplitude
      upon repeated application of the peptides with short intervals, whereas the slow
      response was rather augmented by repeated application. Lowering the temperature
      markedly depressed the slow response, while the fast response remained almost
      unaffected. It is therefore likely that the fast and slow depolarizations are
      mediated by two different subtypes of tachykinin receptors or a single class of
      receptors linked with two different intracellular mechanisms. Measurement of
      tachykinins in several sympathetic ganglia by combined use of HPLC and
      radioimmunoassay revealed that the highest amount of SP occurs in the C-SMG where
      the content of SP (136.0 pmol/g protein) was higher than those of NKA (44.3) and
      NKB (18.7). SP thus appears to function as a major tachykinin in rat C-SMG.

PMID- 1382251
TI  - [Reducing bleeding during extracorporeal circulation interventions by high doses
      of aprotinin].
AB  - The great risk of severe infectious diseases transmission through blood
      transfusion, has increased during the last years the effort to reduce the bank
      blood and its derivates use. Many techniques have proposed to achieve this
      purpose during and post cardiopulmonary bypass: normovolemic hemodilution,
      perioperative blood autotransfusion, postoperative return of extra corporeal
      circuit and chest drains blood and the particular use of some drugs. In the last
      few years several reports have been presented in the literature concerning the
      reduction of intra and postoperative bleeding in cardiac surgery by high dose
      Aprotinin administration. A randomized study with the use of this pharmacologic
      agent is presented: a group of patients was treated with Aprotinin (shared in two
      subgroups receiving respectively a different dose of the drug) and a control
      group. The results were highly encouraging both because of the reduction of peri
      and postoperative bleeding and because of the bank blood use important reduction.

PMID- 1382253
TI  - Ascending projections from the gigantocellular reticular and dorsal
      paragigantocellular nuclei of the medulla oblongata in the rat: an anterograde
      PHA-L tracing study.
AB  - Ascending projections from the gigantocellular reticular (NGc) and dorsal
      paragigantocellular (DPG) nuclei of the medulla oblongata were examined in the
      rat by utilizing anterograde axonal transport of Phaseolus vulgaris
      leucoagglutinin (PHA-L). New observations of fiber connections could be made by
      the merits of the PHA-L. PHA-L-labeled axon terminals were observed in the dorsal
      part of the nucleus of the solitary tract, the rostrolateral subnucleus of the
      interpeduncular nucleus, bed nucleus of the stria terminalis, lateral septal
      nucleus and subfornical organ, in which no previous authors had found projections
      from the NGc or DPG. The strongest projections were observed in the motor nucleus
      of the trigeminal nerve, lateral and dorsolateral subnuclei of the facial
      nucleus, and prepositus hypoglossal nucleus, which suggested that both NGc and
      DPG had some relation to the movements around the mouth and to the eyeball
      movements. The projections to the dorsal part of the nucleus of the solitary
      tract and to the subfornical organ from the NGc and DPG are considered to reveal
      certain roles in cardiovascular regulation. Mainly, the facial nucleus received
      projections from the NGc, the subfornical organ from caudal NGc, the red nucleus
      from the DPG, and the rostrolateral subnucleus of the interpeduncular nucleus
      from the rostral DPG, respectively. The NGc and DPG would have partially
      different roles with regard to the ascending innervation. The present PHA-L study
      was partially confirmed using wheat germ agglutinin conjugated to horseradish
      peroxidase which was injected into the bed nucleus of the stria terminalis and
      subfornical organ.

PMID- 1382254
TI  - Substance P and neuropsychiatric disorders: an overview.
AB  - Substance P (SP) is a naturally-occurring tachykinin peptide isolated from brain
      tissues and gastrointestinal tract. In the brain, substantia nigra and basal
      ganglia contain relatively high amounts of substance P. There is evidence
      suggesting that substance P functions as a neurotransmitter. It has been
      implicated in the pathophysiology of several neuropsychiatric disorders.
      Substance P may also serve as a useful tool in studying the effects of
      antidepressant drugs and electroconvulsive therapy. However, the contribution of
      substance P to the understanding of neuropsychiatric disorders is far from clear.
      Future studies should focus on the interactions and coexistence of substance P
      with other neurotransmitters and neuropeptides.

PMID- 1382255
TI  - Combined chemotherapy and radiotherapy versus best supportive care in the
      treatment of inoperable non-small-cell lung cancer.
AB  - Between October 1984 and July 1988, 119 patients with limited-stage inoperable
      non-small-cell lung cancer (NSCLC) were randomized to receive either active
      treatment (arm 1) or best supportive treatment (arm 2). Arm 1 patients received 3
      courses of chemotherapy with cisplatin (100 mg/m2, day 1) and etoposide (125
      mg/m2 i.v., day 1; 250 mg/m2 p.o., day 2-3), followed by radiotherapy (4,000
      cGy/20 fractions/4 weeks). Arm 2 patients only received best supportive care.
      Fifty-three and 66 patients were randomized to arms 1 and 2, respectively. Thirty
      eight patients in arm 1 and 57 in arm 2 were evaluable for survival. Median
      survivals of arms 1 and 2 were 12.4 and 8.7 months, respectively (p = 0.047). In
      the multivariate analysis, only age and histology were independent prognostic
      variables in predicting survival. The overall response rate after chemotherapy
      was 20.6% (complete remission 5.9%, partial remission 14.7%). Toxicities were
      mainly anemia, leukopenia, vomiting and alopecia. This study suggests that active
      treatment has marginal survival benefit in NSCLC though with considerable
      toxicities.

PMID- 1382256
TI  - Randomized study with the pineal hormone melatonin versus supportive care alone
      in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy
      containing cisplatin.
AB  - At present, there is no effective medical therapy in metastatic nonsmall cell
      (NSC) lung cancer patients who progressed under a first-line chemotherapy
      containing cisplatin. Since recent data have demonstrated the antineoplastic
      properties and the lack of toxicity of the pineal hormone melatonin (MLT), a
      randomized study was designed to evaluate the influence of an MLT treatment (10
      mg/day orally at 7.00 p.m.) on the survival time at 1 year from the progression
      under chemotherapy in respect to supportive care alone in a group of metastatic
      NSC lung cancer patients, who did not respond to a first-line chemotherapy
      containing cisplatin. The study includes 63 consecutive metastatic NSC lung
      cancer patients, who were randomized to receive MLT (n = 31) or supportive care
      alone (n = 32). The percentage of both stabilizations of disease and survival at
      1 year was significantly higher in patients treated with MLT than in those
      treated only with supportive care. No drug-related toxicity was seen in patients
      treated with MLT, who, on the contrary, showed a significant improvement in
      performance status. This randomized study shows that the pineal hormone MLT may
      be successfully administered to prolong the survival time in metastatic NSC lung
      cancer patients who progressed under a first-line chemotherapy with cisplatin,
      for whom no other effective therapy is available up to now.

PMID- 1382257
TI  - Subclinical hepatocellular carcinoma in Hong Kong Chinese.
AB  - Of the 208 Chinese patients with histologically proven hepatocellular carcinoma
      (HCC) seen during a 5-year period, 191 patients presented with symptomatic HCC
      and 17 patients with asymptomatic HCC (subclinical HCC, SCHCC) being picked up by
      alpha-fetoprotein (AFP) screening. Compared with the patients with symptomatic
      HCC, patients with SCHCC had a better performance status (p less than 0.01),
      higher serum albumin levels (p less than 0.05) and lower alkaline phosphatase
      levels (p less than 0.01). In those patients with symptomatic HCC, 4.7% were
      operable and only 2 patients had a tumour diameter of less than 5 cm. In
      contrast, patients with SCHCC had a higher operability rate (76.5%, p less than
      0.0001) and all had a tumour of less than 5 cm in diameter (p less than 0.0001).
      Patients with SCHCC, most of whom had their tumour resected, had a better long
      term survival (p less than 0.0001). We conclude that patients with SCHCC picked
      up by AFP serosurveillance have a better performance status, higher operability
      and better prognosis.

PMID- 1382258
TI  - Nasal patency, aerobic capacity, and athletic performance.
AB  - The patency of the nasal airway may directly affect pulmonary ventilation, with
      obstruction and increased nasal resistance resulting in increased pulmonary
      resistance, hypoxia, and hypercapnea. Nine aerobic athletes were evaluated to
      assess the role of the nasal airway on aerobic capacity and athletic performance.
      A step-ladder graded maximal aerobic capacity test was performed under three test
      conditions: obstructed, decongested with oxymetazoline hydrochloride, and saline
      control. No differences in maximum VO2, work load, oxygen saturation, maximal
      blood pressure, heart rate, or respiratory rate were noted between test
      conditions. Pre-exercise nasal resistance was lower in the decongested compared
      to control conditions, but no differences were found after exercise. Athletic
      performance was not influenced by nasal patency in this model.

PMID- 1382259
TI  - Use of a replica-plate assay for the rapid assessment of salivary protein
      bacteria interactions.
AB  - A replica-plate assay was used to screen for the interaction of salivary
      molecules with dental plaque bacteria. Bacterial colonies cultured from
      supragingival plaque on sheep-blood (SB) agar were replica-plated onto
      nitrocellulose membranes overlaying SB or mitis-salivarius agar. Membranes with
      attached colonies were removed and incubated with 125I-amylase or 125I-proline
      rich glycoprotein (PRG). Positive interactions were detected by autoradiography.
      Only strains of Streptococcus gordonii and Actinomyces viscosus bound amylase,
      and strains of A. viscosus bound PRG. The results suggest that amylase and PRG
      bind to selected species of aerobic dental plaque bacteria.

PMID- 1382260
TI  - Whole-cell recordings of chloride currents in cultured human skeletal muscle.
AB  - Chloride currents in human myoballs were investigated with the tight-seal whole
      cell recording method in a wide range of membrane voltages (-125 to +145 mV). Two
      current components having different kinetics could be distinguished. In more than
      90% of the myoballs the following results were obtained. At negative potentials,
      the amplitude of the Cl- current was small and independent of time. The amplitude
      of the current increased as the membrane potential was made more positive. At
      potentials positive to +75 mV, the current increased monoexponentially with time.
      Inactivation occurred only during very long (greater than 3 s) pulses. When such
      a test pulse was preceded by a conditioning pulse to +60 mV, the current at
      potentials more than +90 mV was markedly smaller than in the absence of a
      prepulse, and no activation was provoked by strongly pulses. Recovery from
      inactivation could only be measured at potentials negative to -40 mV. The Cl-
      conductance at -85 mV was 5.9 +/- 3.64 microS/cm2 (SD; n = 10). In about 5% of
      the myoballs a kinetically different current was visible, characterized by fast
      inactivation at highly positive potentials. The current amplitudes were
      substantially larger in such cases, the Cl- conductance at -85 mV being 12.2 +/-
      9.02 microS/cm2 (n = 4).

PMID- 1382261
TI  - Single-channel recordings of chloride currents in cultured human skeletal muscle.
AB  - The Cl- channels in human myoballs were investigated with several recording
      techniques. Three types of channels were found and dubbed "small",
      "intermediate", and "large", according to their different conductance. The
      intermediate Cl- channel was observed most frequently. It was active at the
      resting potential immediately after seal formation in cell-attached as well as in
      excised patches. Its Cl- selectivity was rather high (PCl/PNa = 9.46; PCl/PMeSO4
      = 7.85 where P denotes permeability) and the slope conductance at the reversal
      potential with [Cl-]o/[Cl-]i equal to 160 mM/42 mM was 31 pS. The channel showed
      an open-channel substructure with two subconductance levels having equal
      amplitudes. It can conduct two kinetically different currents that correspond to
      the activating and the inactivating Cl- current components described by Zachar et
      al. (1992). The small Cl- channel had a conductance of 10 pS at the reversal
      potential, a PCl/PNa of 2.7, and a PCl/PMeSO4 of 22.6. Its open probability was
      biggest negative to -85 mV, resulting in an inactivating whole-cell Cl- current
      component. Because of the small channel density and conductance the contribution
      of this channel type to the whole-cell current seems to be small. Patches with
      only one small channel were never observed which suggests that this channel type
      occurs in clusters. A third type of channel with very large conductance (250 pS)
      was seen only four times.

PMID- 1382262
TI  - Properties of the inactivating outward current in single smooth muscle cells
      isolated from the rat anococcygeus.
AB  - The properties of the voltage- and time-dependent outward current in single
      smooth muscle cells isolated from the rat anococcygeus were studied. The outward
      current was activated by depolarizations to membrane potentials positive to -40
      mV. Activation followed third order kinetics; at +20 mV, the time for the current
      to reach half its maximal amplitude was around 55 ms. The current inactivated
      with a time course that could best be described by a single exponential with a
      time constant around 1500 ms. The steady-state inactivation curve was voltage
      dependent over the range -110 to -30 mV, with a half-inactivation point of -67
      mV. Recovery from inactivation followed an exponential time course with a time
      constant of around 770 ms at -90 mV. Deactivating tail current analysis revealed
      that a 10-fold change in the extracellular potassium ion concentration resulted
      in a 42 mV change in the reversal potential of the current. The current was
      blocked by 4-aminopyridine, tetraethylammonium, quinine and verapamil with IC50's
      -the concentrations producing 50% inhibition of the peak current--of 2 mM, 4 mM,
      12 microM and 20 microM respectively. The current was not blocked by Toxin I (100
      nM) or glibenclamide (10 microM). The current was still present in cells
      containing 5 mM EGTA; in these cells, replacing extracellular calcium with
      cadmium depressed the peak current by around 12%. This could be explained, at
      least in part, by a negative shift in the voltage dependence of inactivation.

PMID- 1382263
TI  - Calcium-dependence of the calcium-activated chloride current in smooth muscle
      cells of rat portal vein.
AB  - Ca(2+)-activated Cl- current in freshly isolated smooth muscle cells from rat
      portal vein was studied using the whole-cell patch-clamp technique.
      Simultaneously, the free-cytosolic Ca2+ concentration (Cai) was estimated using
      emission from the dye Indo-1. Pretreatment of the cells with amytal and carbonyl
      cyanide-m-chlorophenylhydrazone, which reduced the intracellular adenosine
      triphosphate concentration, was used to weaken the cellular Ca2+ homeostatic
      system. Cai of treated cells slowly increased during perfusion with an external
      Ca(2+)-containing solution. This rise in Cai gradually activated a Ca(2+)
      dependent Cl- current which allowed the study of the relationship between
      activation of this current and Cai levels. The threshold Cai for activation of Cl
      channels was around 180 nM and full activation occurred at 600 nM. The Cai
      dependence of the Cl- channels was not changed during application of
      noradrenaline and did not depend on the membrane potential. The gating of Ca(2+)
      dependent Cl- channels of rat portal vein myocytes seems to be mainly controlled
      by intracellular Ca2+.

PMID- 1382264
TI  - Disparate effects of calcium channel blockers on pressure dependence of renin
      secretion and flow in the isolated perfused rat kidney.
AB  - Using the model of isolated perfused rat kidneys this study was performed to
      investigate whether or not voltage-operated calcium channels are essentially
      involved in the pressure control of renin secretion from the kidneys. At a
      perfusion pressure of 100 mm Hg (13.3 kPa) renin secretory rates were 4.2 +/- 0.7
      (ng angiotensin I h-1) min-1 g-1. Stepwise reduction of renal perfusion pressure
      to 80, 60, and 40 mm Hg (10.6, 8.0, 5.3 kPa) resulted in an increase of renin
      release yielding a 30-fold stimulation at 40 mm Hg vs 100 mm Hg. Increasing the
      perfusion pressure above 100 mm Hg did not further significantly decrease renin
      secretion. The perfusate flow rate was also pressure-dependent. Flow rates
      increased linearly with pressure and reached a plateau at 100 mm Hg, which was
      maintained up to 160 mm Hg (21.3 kPa). The averaged flow rate at the plateau was
      15.5 ml min-1 g-1. In the presence of the three different calcium antagonists
      nifedipine (5 microM), nitrendipine (3 microM) and verapamil (5 microM), myogenic
      autoregulation of flow was abolished as indicated by the rise of the
      pressure/flow curve between 40 and 160 mm Hg. At the same time, however, these
      calcium channel blockers did not alter the relationship between perfusion
      pressure and renin secretion. Moreover, the calcium channel agonist Bay K 8644 (5
      microM) caused a strong and long-lasting vasoconstriction, without changing renin
      secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382265
TI  - Voltage-sensitive chloride channels of large conductance in the membrane of pig
      aortic endothelial cells.
AB  - Single, large-conductance chloride-selective channels were studied in the
      membrane of pig aortic endothelial cells. These channels were usually inactive in
      cell-attached recordings and activated spontaneously upon formation of inside-out
      patches or amphotericin B-perforated vesicles. Channel activity was voltage
      dependent, with a maximum open probability within the range of -20 mV to + 20 mV.
      Addition of 1 mM Zn2+ to either the cytoplasmic or extracellular side blocked
      channel activity reversibly. Extracellular 4,4'-diisothiocyanostilbene-2,2'
      disulphonic acid (DIDS) blocked the channels; the concentration necessary for
      half-maximum blockade was 100 mumol/l. The frequency of observing channels in
      cell-attached patches increased from less than 5% to 27% when cells were treated
      for several minutes with 1 mumol/l bradykinin and to 80% in the presence of the
      calcium ionophore A23187 (1 mumol/l). Both agents increase the cytoplasmic Ca2+
      concentration, thereby stimulating nitric oxide (NO) synthesis and cGMP formation
      in endothelial cells. Sodium nitroprusside (100 mumol/l), which spontaneously
      releases NO, did not increase Cl- channel activity in intact cells. Polymyxin B
      (100 mumol/l), an inhibitor of protein kinase C, clearly enhanced Cl- channel
      activity in intact cells, resulting in the observation of Cl- channels in 70% of
      cell-attached patches. Our results demonstrate the existence of a large
      conductance (LC-type) Cl- channel in vascular endothelium which is subject to a
      complex cellular regulation, possibly involving inhibition via phosphorylation by
      protein kinase C, and activation by a Ca2(+)-dependent process which is different
      from the NO/cGMP pathway.

PMID- 1382266
TI  - Transmitter-induced changes of the membrane voltage of HT29 cells.
AB  - The colonic carcinoma cell line HT29 was used to examine the influence of
      agonists increasing cytosolic cAMP and Ca2+ activity on the conductances and the
      cell membrane voltage (Vm). HT29 cells were grown on glass cover-slips. Cells
      were impaled by microelectrodes 4-10 days after seeding, when they had formed
      large plaques. In 181 impalements Vm was -51 +/- 1 mV. An increase in bath K+
      concentration from 3.6 mmol/l to 18.6 mmol/l or 0.5 mmol/l Ba2+ depolarized the
      cells by 10 +/- 1 mV (n = 49) or by 9 +/- 2 mV (n = 3), respectively. A decrease
      of bath Cl- concentration from 145 to 30 mmol/l depolarized the cells by 11 +/- 1
      mV (n = 24). Agents increasing intracellular cAMP such as isobutylmethylxanthine
      (0.1 mmol/l), forskolin (10 mumol/l) or isoprenaline (10 mumol/l) depolarized the
      cells by 6 +/- 1 (n = 13), 15 +/- 3 (n = 5) and 6 +/- 2 (n = 3) mV, respectively.
      In hypoosmolar solutions (225 mosmol/l) cells depolarized by 9 +/- 1 mV (n = 6).
      Purine and pyrimidine nucleotides depolarized the cells dose-dependently with the
      following potency sequence: UTP greater than ATP greater than ITP greater than
      GTP greater than TTP greater than CTP = 0. The depolarization by ATP was stronger
      than that by ADP and adenosine. The muscarinic agonist carbachol led to a
      sustained depolarization by 27 +/- 6 mV (n = 5) at 0.1 mmol/l, and to a transient
      depolarization by 12 +/- 4 mV (n = 5) at 10 mumol/l. Neurotensin depolarized with
      a half-maximal effect at around 5 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382267
TI  - cAMP-dependent activation of small-conductance Cl- channels in HT29 colon
      carcinoma cells.
AB  - The present study was performed to examine the conductance properties in the
      colon carcinoma cell line HT29 and the activation of Cl- channels by cAMP. A
      modified cell-attached nystatin patch-clamp technique was used, allowing for the
      simultaneous recording of the cell membrane potential (PD) and the conductance
      properties of the cell-attached membrane. In resting cells, PD was -56 +/- 0.4 mV
      (n = 294). Changing the respective ion concentrations in the bath indicate that
      these cells possess a dominating K+ conductance and a smaller Cl- conductance. A
      significant non-selective cation conductance, which could not be inhibited by
      amiloride, was only observed in cells examined early after plating. The K+
      conductance was reversibly inhibited by 1 - 5 mmol/l Ba2+. Stimulation of the
      cells by the secretagogues isoproterenol and vasointestinal polypeptide (VIP)
      depolarized PD and induced a Cl- conductance. Similar results were obtained with
      compounds increasing cytosolic cAMP: forskolin, 3-isobutyl-1-methylxanthine,
      cholera toxin and 8-bromoadenosine cyclic 3',5'-monophosphate (8-Br-cAMP). VIP (1
      nmol/l, n = 10) and isoproterenol (1 mumol/l, n = 12) depolarized the cells dose
      dependently and reversibly by 12 +/- 2 mV and 13 +/- 2 mV. The maximal
      depolarization was reached after some 20 s. The depolarization was due to
      increases in the fractional Cl- conductance. Simultaneously the conductance of
      the cell-attached membrane increased from 155 +/- 31 pS to 253 +/- 40 pS (VIP, n
      = 4) and from 170 +/- 43 pS to 268 +/- 56 pS (isoproterenol, n = 11), reflecting
      the gating of Cl- channels in the cell-attached membrane.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1382269
TI  - An act of love ... or an admission of failure? Euthanasia.

PMID- 1382268
TI  - Small-conductance Cl- channels in HT29 cells: activation by Ca2+, hypotonic cell
      swelling and 8-Br-cGMP.
AB  - The present study demonstrates the activation of Cl- channels in HT29 cells by
      agonist (ATP, neurotensin, carbachol) increasing cytosolic Ca2+, by hypotonic
      cell swelling and by cGMP. Cell-attached nystatin patch-clamp (CAN) as well as
      slow and fast whole-cell recordings were used. The cell membrane potential was
      depolarized in a dose-dependent manner with half-maximal effects at 0.4 mumol/l
      for ATP, 60 pmol/l for neurotensin and 0.8 mumol/l for carbachol. The
      depolarization, which was caused by Cl- conductances increases, occurred within 1
      s and was accompanied by a simultaneous and reversible increase of the input
      conductance of the cell-attached membrane from 295 +/- 32 pS to 1180 +/- 271 pS
      (ATP; 10 mumol/l, n = 21) and 192 +/- 37 pS to 443 +/- 128 pS (neurotensin; 1
      nmol/l, n = 8). The effects of the agonists could be mimicked by ionomycin (0.2
      mumol/l), suggesting that an increase in intracellular Ca2+ was responsible for
      the activation of Cl- channels. The depolarization was followed by a secondary
      hyperpolarization. Hypotonic cell swelling also depolarized the cells and induced
      an increase in the membrane conductance. With 120 mmol/l NaCl the depolarization
      was 10 +/- 0.8 mV and the cell-attached conductance increased from 228 +/- 29 pS
      to 410 +/- 65 (n = 26) pS. NaCl at 90 mmol/l and 72.5 mmol/l had even stronger
      effects. Comparable conductance increases were also obtained when the different
      agonists or hypotonic cell swelling were examined in whole cell experiments. 5
      Nitro-2-(3-phenylpropylamino)-benzoate (1 mumol/l) did not prevent the effects of
      Ca(2+)-increasing hormones and of hypotonic solutions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382270
TI  - Evaluation of ICD therapy.

PMID- 1382271
TI  - Catheter ablation for cardiac arrhythmias, personnel, and facilities. North
      American Society of Pacing and Electrophysiology Ad Hoc Committee on Catheter
      Ablation.

PMID- 1382272
TI  - Left ventricular free-wall rupture occurring during programmed ventricular
      stimulation in a patient with recent myocardial infarction.
AB  - In this report we describe a patient who died during programmed ventricular
      stimulation due to a rupture of the left ventricular free wall at the site of a
      recent myocardial infarction. The patient was a 75-year-old male who presented
      with an extensive anterior wall myocardial infarction complicated by sustained
      ventricular tachycardia occurring 8 days after admission. Cardiac catheterization
      revealed total occlusion of left anterior descending coronary artery and an
      anteroapical aneurysm. The patient died due to electromechanical dissociation
      during electrophysiological testing 11 days after myocardial infarction.
      Postmortem examination showed a rupture of the left ventricular free wall at the
      site of the myocardial infarction and distant from the site of catheter
      placement. It is suggested that caution be taken in choosing patients for
      electrophysiological studies who have had recent large myocardial infarctions
      with ventricular aneurysm.

PMID- 1382273
TI  - The performance of the probability density function in differentiating
      supraventricular from ventricular rhythms.
AB  - The ability of the probability density function (PDF) of an automatic implantable
      cardioverter defibrillator (AICD) to reject supraventricular arrhythmias being
      recognized as ventricular was evaluated in 12 patients who were treated with an
      AICD (Ventak P 1600). The PDF criterion was monitored via telemetry with the
      sinus rate during exercise test. PDF was satisfied in seven patients at a rate of
      75-144/min (mean 109/min), and not in the remaining five patients (mean rate
      141/min). PDF was fulfilled in five of ten patients at a lower heart rate than
      predicted by the duty cycle index, derived from the ventricular patch lead
      electrogram at the implantation. Thus PDF is often fulfilled already at a
      moderately elevated sinus rate. If used to prevent inadvertent AICD discharges
      during rapid supraventricular rhythms, its performance should be tested in the
      individual patient.

PMID- 1382274
TI  - Sinus node dysfunction after orthotopic cardiac transplantation: postoperative
      incidence and long-term implications.
AB  - We investigated incidence, normalization rates, and clinical significance of
      sinus node (SN) dysfunction after cardiac transplantation. Thirty-nine of 90
      patients systematically evaluated presented with impaired SN function in the
      postoperative period. Of these, 22 normalized their SN function during follow-up
      while 17 remained impaired after 3 months. The proportion normalized was higher
      in patients with prolonged SN recovery time (11/16, 68.8%) and those reverting
      from escape rhythm to sinus rhythm until discharge (5/8, 62.5%) when compared to
      patients in escape rhythm throughout the postoperative period (5/11, 45.5%) or
      pacemaker dependence (1/4, 25%). There was no reliable postoperative predictor of
      normalization and necessity of long-term pacing. A postoperative heart rate
      consistently less than 70 beats/min (irrespective of the native rhythm) was
      significantly related to outcome (P = 0.01), but revealed unacceptable
      sensitivity (61.5%) and specificity (81%). After all, both patients with severe
      symptoms (near syncopes and syncope), were derived from this group. These two
      patients, who had been discharged in sinus rhythm, had late pacemakers implanted.
      An additional 17 patients had early pacemaker placement, only seven of which were
      constantly paced during follow-up. Given the low normalization rates, patients
      with postoperative escape rhythm are those most likely to benefit from pacemaker
      therapy over the long term. Even those in, or reverting back to, sinus rhythm
      until discharge may experience severe symptoms, particularly in the setting of a
      postoperative rate consistently less than 70 beats/min since this indicates a
      relatively lower probability of recovery.

PMID- 1382275
TI  - Radiofrequency ablation of symptomatic but benign ventricular arrhythmias.
AB  - Two cases are presented where ablation of severely symptomatic ventricular
      arrhythmias not responding to medical therapy was accomplished with
      radiofrequency current application. After a routine programmed stimulation
      protocol, a quadripolar ablation catheter with a 4-mm tip was advanced
      percutaneously into the left ventricle in one case and into the right ventricle
      in the second case; and after precise pace mapping, the arrhythmogenic focus was
      successfully ablated using radiofrequency current. The postablation ambulatory
      recording revealed virtual eradication of ventricular ectopy in both cases. In
      conclusion, in severely symptomatic cases of "benign" ventricular arrhythmias,
      radiofrequency ablation offers an effective therapeutic alternative.

PMID- 1382276
TI  - The use of head-upright tilt table testing in the evaluation and management of
      syncope in children and adolescents.
AB  - Recurrent syncope in an otherwise healthy child or adolescent is a common anxiety
      provoking disorder. Vasovagally mediated hypotension and bradycardia are believed
      common, yet difficult to diagnose, causes of syncope in this age group. Upright
      tilt table testing has been suggested as a potential method to test for vasovagal
      episodes. This study evaluated the utility of this technique in the evaluation
      and management of recurrent syncope in children and adolescents. Thirty patients
      with recurrent unexplained syncope were evaluated by use of an upright tilt table
      test for 30 minutes, with or without an infusion of isoproterenol (1 to 3
      micrograms/min given intravenously), in an attempt to produce hypotension,
      bradycardia, or both. There were 15 males and 15 females, mean age 14 +/- 6
      years. Each of the tilt positive patients received therapy with either
      fluorohydrocortisone, beta blockers, or transdermal scopolamine. Syncope occurred
      in six patients (20%) during the base line tilt and in 15 patients (50%) during
      isoproterenol infusion (total positives 70%). All initially positive patients
      were rendered tilt negative by therapy. Over a mean follow-up period of 20
      months, no further episodes have occurred. We conclude that tilt table testing is
      a useful and effective test in the evaluation of unexplained syncope in
      childhood.

PMID- 1382277
TI  - Failure of a second and third generation implantable cardioverter defibrillator
      to sense ventricular tachycardia: implications for fixed-gain sensing devices.
AB  - Failure to sense ventricular tachycardia and/or ventricular fibrillation by
      implantable cardioverter defibrillators (ICDs) is rare. We report a case in which
      persistent undersensing of monomorphic and polymorphic ventricular tachycardia
      occurred with a second and third generation ICD using fixed-gain sensing. This
      occurred despite adequate R wave sensing during sinus rhythm. The use of an
      endocardial sensing lead did not correct the problem. Failure to sense
      ventricular tachycardia in the third generation device with fixed-gain sensing
      occurred late after implantation and was discovered only at follow-up
      electrophysiology testing of the ICD. This problem could not be corrected by
      reprogramming of the device, and was not related to lead dislodgement. Placement
      of a new device with an automatic-gain sensing algorithm and use of previously
      implanted epicardial leads with better sensing characteristics provided
      appropriate sensing of ventricular tachyarrhythmias. The case illustrates the
      importance of testing the sensing of all ventricular arrhythmias in patients with
      fixed-gain ICD's. Follow-up electrophysiology testing and evaluation of
      epicardial and endocardial leads may be necessary in certain cases to ensure
      adequate sensing of ventricular tachyarrhythmias late after implantation.

PMID- 1382278
TI  - Frequency and output-dependent change in conduction over slow pathways in a
      patient with sustained ventricular tachycardia unrelated to coronary artery
      disease.
AB  - In a patient with sustained ventricular tachycardia, we obtained two different
      paced QRS morphologies from a single pacing site. In one QRS morphology the
      stimulus to the QRS complex was long, 150 msec, and in the other it was 100 msec.
      At the paced cycle length of 600 msec and the stimulus output of 4 V, one QRS
      morphology with the stimulus to the onset of QRS activation (St-QRS) interval of
      150 msec was observed. At the paced cycle length of 400 msec, the other QRS
      morphology with a St-QRS interval of 100 msec was observed alternatively with the
      former. At the paced cycle length of 353 msec or 316 msec, the latter with a
      shorter St-QRS interval was exclusively observed. When the stimulus output was
      increased from 4 to 10 V, keeping with the paced cycle length at 400 msec, the St
      QRS interval was shortened from 100 to 80 msec. For the two QRS morphologies with
      two St-QRS intervals, two slowly conducting pathways would be responsible. The
      site of the block in the faster pathway must be located at the proximity of the
      pacing site and the conduction at a shorter paced cycle length would be explained
      by "supernormal conduction."

PMID- 1382279
TI  - Incidence and timing of activity parameter changes in activity responsive pacing
      systems.
AB  - The incidence and timing of rate response parameter reprogramming in activity
      responsive pacing systems during the year after implantation was evaluated in two
      groups of patients: 24 patients in whom a VVI,R system was implanted (Activitrax,
      Medtronic, Inc.), and 21 patients in whom a DDD,R system was implanted
      (Synchrony, Siemens Pacesetter, Inc.). Activity parameter changes in Activitrax
      patients were made based on the presence of symptoms, while in Synchrony
      patients, changes were based on objective data obtained using a sensor indicated
      rate histogram with a slow and fast walk protocol. No significant difference in
      the incidence of activity parameter reprogramming was noted at various time
      intervals during the first year in Activitrax patients; in Synchrony patients a
      greater incidence of reprogramming changes was noted at the 1-month follow-up
      visit compared to later follow-up visits (P less than 0.02). Further, the
      incidence of changes at 1 month was greater for Synchrony compared to Activitrax
      patients (P less than 0.001), while no difference was detected between groups at
      subsequent follow-up intervals. Use of the slow and fast walk protocol, by
      permitting serial evaluation of sensor response, demonstrated alterations in
      sensor drive rates with similar levels of activity over the initial 4 to 6
      postimplant weeks. This may result from postoperative changes at the pacemaker
      insertion site. Based on this experience, predischarge programming may not
      predict long-term rate response requirements. We recommend evaluation of sensor
      function using an exercise protocol performed at 4 to 6 postimplant weeks in all
      rate responsive pacing systems that utilize a piezoelectric crystal.

PMID- 1382280
TI  - Effect of the atrioventricular relationship on atrial refractoriness in humans.
AB  - Atrial arrhythmias occur frequently in the setting of increased atrial size and
      pressure. This may result from contraction-excitation feedback. The objective of
      this study was to investigate the effect of alterations in atrial pressure,
      induced by varying the atrioventricular (AV) interval, on atrial refractoriness,
      and on the frequency of induction of atrial fibrillation. Twenty-seven patients
      without structural heart disease participated in the study. In each patient the
      atrial effective (ERP) and absolute refractory period (ARP) were measured during
      AV pacing at a cycle length of 400 msec and AV intervals of 0, 120, and 160 msec.
      The ERP was defined as the longest extrastimulus coupling interval that failed to
      capture with an extrastimulus current strength of twice the stimulation
      threshold. The ARP was defined in a similar manner with an extrastimulus current
      strength of 10 mA. The ERP and ARP were determined during continuous pacing using
      the incremental extrastimulus technique. A subset of patients had the pacing
      protocol performed during autonomic blockade. As the AV interval was increased
      from 0 to 160 msec, the peak right atrial pressure decreased from 16 +/- 4 mmHg
      to 7 +/- 3 mmHg and the mean right atrial pressure decreased from 7 +/- 3 mmHg to
      3 +/- 22 mmHg (P less than 0.001). The atrial ERP and ARP did not change with
      alterations in the AV interval. There was no difference in the frequency of
      induction of atrial fibrillation. Similar results were obtained during autonomic
      blockade. These findings suggests that the phenomenon of contraction-excitation
      feedback may not be of importance in the development of atrial arrhythmias in
      patients without structural heart disease.

PMID- 1382281
TI  - Permanent AV block or modification of AV nodal function by selective AV nodal
      artery ethanol infusion.
AB  - The acute and chronic effects of selective AV nodal artery ethanol infusion on AV
      nodal function was studied in 9 closed chest anesthetized dogs. Using standard
      percutaneous techniques of arterial catheterization, a 2.2 French infusion
      catheter was positioned in the AV nodal artery. Ten minute infusions into the AV
      nodal artery of 25%, 50%, or 100% ethanol in normal saline at rates of 0.5 mL/min
      acutely resulted in complete AV nodal block (AVB) in 5 dogs, 2:1 AV nodal block
      in 1 dog, and prolongation of AV nodal effective refractory period and/or
      Wenckebach cycle length in the remaining 3 dogs. One dog died with persistent
      complete AV block 1 week after the ethanol infusion. When restudied 4 weeks
      later, 7 of the 8 surviving dogs had persistent modification of AV nodal
      function, including complete AV block in 5 dogs and lengthening of AV nodal
      effective refractory period and/or Wenckebach cycle length without AV block in 2
      dogs. Pathologic examination of the animals exhibiting chronic modification or
      ablation of AV nodal function revealed healing infarction of the AV node or its
      approaches. Distant myocardial necrosis was not observed and left ventricular
      function was normal. Slow infusion of low concentrations of ethanol into the AV
      nodal artery results in AV nodal modification or ablation due to localized
      necrosis in or around the AV node. This technique may have a role in AV nodal
      modification or ablation, particularly in patients who have failed DC shock or
      radiofrequency ablation.

PMID- 1382282
TI  - Stimulation hierarchy: optimal sequence for double and triple extrastimuli during
      electrophysiological studies.
AB  - To determine the optimal ventricular stimulation sequence, an 11-step programmed
      electrical stimulation (PES) protocol was completed, even if a ventricular
      arrhythmia (VA) was induced with earlier steps. The protocol consisted of one,
      two, and three extrastimuli during sinus rhythm (SR), and at two drive pacing
      rates (VP1 and VP2) plus rapid burst and ramp pacing. By analyzing the 79
      completed protocols that induced the clinical arrhythmia, the following were
      determined: (1) the frequency of induced clinical and nonclinical VA with each
      stimulation step; (2) the yield ratio (YR) of each step, defined as the
      probability of inducing clinical versus nonclinical arrhythmia; (3) the
      cumulative yield of induced clinical and nonclinical arrhythmia with two widely
      used stimulation sequences, i.e., triple extrastimuli delivered early in the
      stimulation protocol (MMC sequence) and triple extrastimuli delayed until after
      double extrastimuli failed to induce the clinical arrhythmia (B sequence); (4)
      the relative efficiency of these sequences were determined. The percentage of
      induced clinical and nonclinical arrhythmia with SR + 3 extrastimuli, VP1 + 2
      extrastimuli, and VP2 + 2 extrastimuli were (53%, 5%), (36%, 5%), and (41%, 9%),
      respectively. The cumulative yield of induced clinical VA with the MMC-type
      sequence reached 55% by the third step of the protocol, whereas 50% was attained
      only at the eighth step of the B-type sequence. The cumulative percentage of
      induced nonclinical VA with either sequence was similar during the early steps of
      the protocol. The MMC sequence was more efficient, requiring overall 36% of
      potential steps for clinical arrhythmia induction, compared with 48% for the B
      sequence (P less than 0.001). For questionable arrhythmia states, e.g., syncope
      of unknown origin and nonsustained VT, a modified sequence is proposed that may
      further reduce the induction of uninterpretable arrhythmias.

PMID- 1382283
TI  - Diagnosis and localization of accessory pathways.
AB  - The WPW syndrome is a curable disease. The evolution of nonpharmacological
      methods of accessory pathway ablation has had a significant impact on management
      strategies in patients with arrhythmias mediated by accessory pathways. Despite
      an incidence of preexcitation in the general population of 0.1% to 0.3%, curative
      therapy is underutilized. This review has highlighted the traditional and newer
      methods of diagnosing and localizing accessory pathways. The number of patients
      benefiting from definitive therapy will parallel increased physician awareness of
      these methods.

PMID- 1382284
TI  - Demonstration of the feasibility of implantation of a skeletal muscle pulse
      generator for fecal incontinence in a patient with an implanted unipolar DDD
      pacemaker.
AB  - Electromagnetic fields and myopotentials from skeletal muscle may interfere with
      the function of a cardiac pacemaker. A 65-year-old woman with a unipolar DDD
      cardiac pacemaker underwent dynamic graciloplasty (transposition of the gracilis
      muscle around the anal canal and subsequent implantation of a bipolar pulse
      generator to stimulate the gracilis muscle), for the treatment of fecal
      incontinence. This gracilis pulse generator is turned "off" with an external
      magnet to allow defecation. Appropriate functioning of these two pulse generators
      (the cardiac pacemaker and the gracilis pulse generator) was tested during
      implantation of the gracilis pulse generator and afterwards. It was demonstrated
      that the combination could be used safely in this patient.

PMID- 1382285
TI  - Bidirectional tachycardia induced by herbal aconite poisoning.
AB  - This report details the clinical, electrocardiographic, and
      electropharmacological characteristics of an unusual case of bidirectional
      tachycardia induced by aconites present in a Chinese herbal decoction consumed by
      a previously healthy subject. The tachycardia showed marked susceptibility to
      vagotonic maneuvers, cholinesterase inhibition, and adenosine triphosphate. The
      incessant nature of the tachycardia, rapid recurrence after transient
      suppression, and failure to respond to direct current cardioversion suggested an
      automatic tachycardia mechanism consistent with known data on the cellular
      electrophysiological mechanism of aconitine-mediated arrhythmogenesis. A
      fascicular or ventricular myocardial origin of the tachycardia with alternating
      activation patterns, or dual foci with alternate discharge, appeared most
      plausible. The rootstocks of aconitum plants have been commonly employed in
      traditional Chinese herbal recipes for "cardiotonic" actions and for relieving
      "rheumatism." Multiple pitfalls could occur during the processing of these herbs
      that might have predisposed to aconite poisoning. The need for strict control and
      surveillance of herbal substances with low margins of safety is highlighted.

PMID- 1382286
TI  - Undersensing as a consequence of lead incompatibility: case report and a plea for
      universality.

PMID- 1382287
TI  - The slide examination section. A new substitution for the oral examination
      section.

PMID- 1382288
TI  - Chronic hepatitis B and C. What is the status of drug therapy?
AB  - Chronic hepatitis remains difficult to treat. Use of interferon has been
      successful against both hepatitis B and C viruses, but the outcome of long-term
      administration has yet to be determined. Not all patients respond to interferon,
      however, and some have side effects that cause them to discontinue therapy. Dr
      Wright discusses the results of studies to evaluate therapy with alpha, beta, and
      gamma interferon as well as with other agents, such as ribavirin, thymosin, and
      ursodeoxycholic acid.

PMID- 1382289
TI  - Human monoclonal islet cell antibodies from a patient with insulin-dependent
      diabetes mellitus reveal glutamate decarboxylase as the target antigen.
AB  - The autoimmune phenomena associated with destruction of the beta cell in
      pancreatic islets and development of type 1 (insulin-dependent) diabetes mellitus
      (IDDM) include circulating islet cell antibodies. We have immortalized peripheral
      blood lymphocytes from prediabetic individuals and patients with newly diagnosed
      IDDM by Epstein-Barr virus transformation. IgG-positive cells were selected by
      anti-human IgG-coupled magnetic beads and expanded in cell culture. Supernatants
      were screened for cytoplasmic islet cell antibodies using the conventional
      indirect immunofluorescence test on cryostat sections of human pancreas. Six
      islet cell-specific B-cell lines, originating from a patient with newly diagnosed
      IDDM, could be stabilized on a monoclonal level. All six monoclonal islet cell
      antibodies (MICA 1-6) were of the IgG class. None of the MICA reacted with human
      thyroid, adrenal gland, anterior pituitary, liver, lung, stomach, and intestine
      tissues but all six reacted with pancreatic islets of different mammalian species
      and, in addition, with neurons of rat cerebellar cortex. MICA 1-6 were shown to
      recognize four distinct antigenic epitopes in islets. Islet cell antibody
      positive diabetic sera but not normal human sera blocked the binding of the
      monoclonal antibodies to their target epitopes. Immunoprecipitation of 35S
      labeled human islet cell extracts revealed that a protein of identical size to
      the enzyme glutamate decarboxylase (EC 4.1.1.15) was a target of all MICA.
      Furthermore, antigen immunotrapped by the MICA from brain homogenates showed
      glutamate decarboxylase enzyme activity. MICA 1-6 therefore reveal glutamate
      decarboxylase as the predominant target antigen of cytoplasmic islet cell
      autoantibodies in a patient with newly diagnosed IDDM.

PMID- 1382290
TI  - Epidermal growth factor stimulates tyrosine phosphorylation in the neonatal
      mouse: association of a M(r) 55,000 substrate with the receptor.
AB  - Administration of epidermal growth factor (EGF) to neonatal mice resulted in
      rapid tyrosine phosphorylation of a number of specific substrates in liver,
      kidney, lung, bladder, skin, and brain as detected by Western blot analysis of
      tissue homogenates with anti-phosphotyrosine antibodies. In the liver, three
      prominent EGF-dependent substrates of M(r) approximately 170,000, 120,000, and
      55,000 were detected. A number of less prominent EGF-dependent substrates also
      were noted. Maximal tyrosine phosphorylation of pp170, pp120, and pp55 occurred
      within 5 min of subcutaneous injection and the levels of these phosphoproteins
      remained elevated for at least 45 min. Direct hepatic injection of EGF resulted
      in the tyrosine phosphorylation of these substrates within 60 sec of treatment.
      Tyrosine-phosphorylated pp170 was identified as the EGF receptor (EGFR). The
      tyrosine-phosphorylated pp55 substrate appeared to be associated with EGFR; both
      pp55 and EGFR were adsorbed to EGF-Affi-Gel, wheat germ lectin-Sepharose, and
      anti-EGFR antibodies bound to protein A-Sepharose. pp55 was not immunoreactive
      with anti-EGFR antiserum by Western blot analysis, indicating that it was not a
      fragment of the receptor. These results were confirmed by repeating the liver
      experiments using 32P-labeled neonatal mice. Increased amounts of 32P-labeled
      pp170 and pp55 were detected in anti-EGFR immunoprecipitates from liver extracts
      of EGF-treated animals as compared with controls. Phospho amino acid analysis of
      the 32P-labeled phosphoproteins revealed that EGF stimulated both serine and
      tyrosine phosphorylation in pp55 as well as in EGFR. The neonatal mouse may be a
      useful model for the study of signal transduction mediated by a variety of growth
      factors.

PMID- 1382291
TI  - UV exposure reduces immunization rates and promotes tolerance to epicutaneous
      antigens in humans: relationship to dose, CD1a-DR+ epidermal macrophage
      induction, and Langerhans cell depletion.
AB  - Increasing UVB radiation at the earth's surface might have adverse effects on in
      vivo immunologic responses in humans. We prospectively randomized subjects to
      test whether epicutaneous immunization is altered by prior administration of
      biologically equalized doses of UV radiation. Multiple doses of antigens on upper
      inner arm skin (UV protected) were used to elicit contact sensitivity responses,
      which were quantitated by measuring increases in skin thickness. If a dose of UVB
      sufficient to induce redness (erythemagenic) was administered to the immunization
      site prior to sensitization with dinitrochlorobenzene (DNCB), we noted a marked
      reduction in the degree of sensitization (P less than 0.0006) that was highly
      dose responsive (r = 0.98). Even suberythemagenic UV (less than a visible
      sunburn) resulted in a decreased frequency of strongly positive responses (32%)
      as compared to controls (73%) (P = 0.019). The rate of immunologic tolerance to
      DNCB (active suppression of a subsequent repeat immunization) in the groups that
      were initially sensitized on skin receiving erythemagenic doses of UV was 31% (P
      = 0.0003). In addition, a localized moderate sunburn appeared to modulate
      immunization with diphenylcyclopropenone through a distant, unirradiated site
      (41% weak responses) as compared to the control group (9%) (P = 0.05). Monitoring
      antigen presenting cell content in the epidermis revealed that erythemagenic
      regimens induced CD1a-DR+ macrophages and depleted Langerhans cells. In
      conclusion, relevant and even subclinical levels of UV exposure have significant
      down modulatory effects on the ability of humans to generate a T-cell-mediated
      response to antigens introduced through irradiated skin.

PMID- 1382292
TI  - Heterogeneity of immunoglobulin-associated molecules on human B cells identified
      by monoclonal antibodies.
AB  - Two covalently linked transmembrane molecules, encoded in mice by the mb-1 and
      B29 genes, have been defined as integral components of the antibody receptor
      units expressed on B cells. We have produced monoclonal antibodies against an
      exposed extracellular epitope on the putative human equivalent of the mouse B29
      product. These antibodies, CB3-1 and -2, were used to show that cytoplasmic
      expression of this molecule begins in human pro-B cells (terminal
      deoxynucleotidyltransferase-positive, mu chain-negative), whereas surface
      expression coincides strictly with surface immunoglobulin expression of all
      isotypes. Immunochemical analysis of the human immunoglobulin-associated
      molecules revealed greater molecular heterogeneity than has been noted for the
      murine analogues. This molecular heterogeneity of immunoglobulin-associated
      molecules varied as a function of differentiation stage and the immunoglobulin
      isotypes expressed by B-lineage cells. Our data support the hypothesis that
      biochemical heterogeneity of the surface immunoglobulin-associated molecules may
      contribute to the variability in biological effects of antigen receptor
      crosslinkage on B cells of different maturational stages. Because the CB3
      antibodies are capable of down-modulating the antigen receptors on all B cells,
      they may prove therapeutically useful as universal B-cell suppressants.

PMID- 1382293
TI  - Effects of cyclosporin A and FK506 on Fc epsilon receptor type I-initiated
      increases in cytokine mRNA in mouse bone marrow-derived progenitor mast cells:
      resistance to FK506 is associated with a deficiency in FK506-binding protein
      FKBP12.
AB  - The inhibitory effects of cyclosporin A (CsA) and FK506 on Fc epsilon receptor
      type I-initiated increases in cytokine mRNA and the expression of their
      intracellular binding proteins were studied in interleukin 3 (IL-3)-dependent,
      mouse bone marrow-derived mast cells (BMMCs). In BMMCs sensitized with IgE anti
      trinitrophenyl, CsA inhibited trinitrophenylated bovine serum albumin-induced
      increases in mRNA for IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL
      6 in a dose-related manner (IC50 values of 4, 65, and 130 nM, respectively).
      FK506 did not inhibit hapten-specific increases of mRNA for TNF-alpha or IL-6,
      and for IL-1 beta the IC50 was greater than 50-fold higher than that of CsA.
      Neither agent inhibited exocytosis of the endogenous secretory granule mediators
      beta-hexosaminidase and histamine at the IC50 values for inhibition of increases
      in cytokine mRNA. BMMCs expressed cyclophilin, and CsA inhibited the phosphatase
      activity of cellular calcineurin with an IC50 of approximately 8 nM. That CsA
      inhibited IL-1 beta mRNA accumulation in IgE-activated BMMCs with an IC50 similar
      to that for inhibition of calcineurin activity, whereas the IC50 values were
      approximately 20-fold higher for the inhibition of TNF-alpha and IL-6 mRNA,
      suggests that the induction of TNF-alpha and IL-6 is less dependent upon
      calcineurin activity than is the induction of IL-1 beta. BMMCs were deficient in
      the 12-kDa FK506-binding protein FKBP12, but not FKBP13, as assessed by RNA and
      protein blot analyses. FK506 did not inhibit calcineurin phosphatase activity in
      BMMCs, even at drug concentrations of 1000 nM. The resistance of BMMCs to
      inhibition of Fc epsilon receptor type I-mediated increases in cytokine mRNA by
      FK506 is most likely due to their deficiency of FKBP12 and the related inability
      to inhibit the activity of calcineurin.

PMID- 1382294
TI  - Adenosine decreases neurotransmitter release at central synapses.
AB  - Adenosine, at concentrations ranging from 5 to 100 microM, decreases the efficacy
      of transmission at the perforant path synapses on dentate granule cells. We have
      used whole cell recording from these cells in slices to determine the mechanism
      of the reduced synaptic strength. We find that size of miniature excitatory
      postsynaptic currents (mepscs) is unaffected by adenosine at concentrations up to
      100 microM, an observation that indicates adenosine's mode of action is not
      through a decreased postsynaptic sensitivity to neurotransmitter. A quantal
      analysis indicates, however, that the quantity of neurotransmitter released is
      sufficiently diminished by adenosine to account entirely for the adenosine
      produced decrease in synaptic strength. Application of 3-isobutyl-1
      methylxanthine (IBMX), a drug that antagonizes the effects of endogenous
      adenosine, produces an increase in synaptic strength. This observation suggests
      that the resting level of adenosine in our slices is appreciable, and an analysis
      of the adenosine dose-response relation is consistent with endogenous adenosine
      levels of about 10 microM. IBMX application produces only slight changes in the
      amplitude of mepscs, whereas a quantal analysis demonstrates that the drug
      significantly increases the amount of neurotransmitter released. Thus IBMX acts
      as an "anti-adenosine" in our experiments. In some experiments we have been able
      to record excitatory and inhibitory synaptic currents produced by the same
      perforant path stimulus. In these instances we find that inhibitory transmission
      is unaffected by concentrations of adenosine that produce a marked decrease in
      the strength of excitatory synapses.

PMID- 1382295
TI  - Molecular organization of Leishmania RNA virus 1.
AB  - The complete 5284-nucleotide sequence of the double-stranded RNA genome of
      Leishmania RNA virus 1 (LRV1) was determined and contains three open reading
      frames (ORFs) on the plus (+) (mRNA) strand. The predicted amino acid sequence of
      ORF3 has motifs characteristic of viral RNA-dependent RNA polymerases. ORF2,
      which may encode the major viral coat protein, overlaps ORF3 by 71 nucleotides,
      suggesting a +1 translational frameshift to produce a gag-pol type of fusion
      protein. Two alternative models for the frameshift are presented. The 5' splice
      leader sequence of kinetoplastid mRNAs is not in LRV1 RNA. This suggests that the
      450-base region at the 5' end of the LRV1 (+)-strand, which contains ORF1 and is
      highly conserved among viral strains, does not encode protein but has a role in
      initiation of translation and/or RNA stability. The similarity of LRV1 genomic
      organization, replication cycle, and RNA-dependent RNA polymerase sequence to
      those of the yeast virus ScV L-A suggests a common ancestral origin. The
      possibility that LRV1 affects pathogenesis in leishmaniasis is intriguing.

PMID- 1382296
TI  - Defective signal transduction by the CD2 molecule in immature T-cell receptor/CD3
      thymocytes.
AB  - The CD2 accessory molecule mediates an activation pathway in mature T cells,
      transducing signals similar to those observed following stimulation of the T-cell
      receptor/CD3 (TCR/CD3) complex. CD2 is also one of the earliest cell surface
      markers to appear during thymic ontogeny and has been proposed to be a
      stimulatory pathway for immature thymocytes that have not yet expressed TCRs on
      their surface (TCR/CD3-). To examine this hypothesis highly purified TCR/CD3-
      human thymocytes were stimulated using mitogenic combinations of anti-CD2
      monoclonal antibodies or individual biotinylated anti-CD2 monoclonal antibodies
      crosslinked with avidin. TCR/CD3+ thymocytes responded readily to either stimulus
      as determined by anti-phosphotyrosine immunoblotting, and the pattern of tyrosine
      phosphorylated substrates was similar to that of mature T cells. In contrast,
      TCR/CD3- thymocytes responded weakly and with a distinct substrate pattern. In
      addition, the altered signal transduced by CD2 in TCR/CD3- thymocytes did not
      lead to a rise in intracellular calcium, failed to induce interleukin 2 receptor
      expression, and did not serve as a comitogen with phorbol ester or interleukin 2,
      functions that were all intact in TCR/CD3+ thymocytes. Failure of TCR/CD3-
      thymocytes to respond to CD2 stimulation was not due to an intrinsic defect in
      these cells as they responded normally to phorbol ester plus calcium ionophore.
      In TCR/CD3- thymocytes, CD2 stimulation also failed to affect steady-state mRNA
      levels of the recombination-activating genes RAG1 and RAG2, whereas in TCR/CD3+
      cells activation of the CD2 pathway terminated their expression. Together, these
      data support the concept that CD2 engagement does not deliver a stimulus to
      TCR/CD3- thymocytes and suggests that this molecule may not directly participate
      in the earliest stages of thymic development.

PMID- 1382297
TI  - Evidence that the deep keratin filament systems of the Xenopus embryo act to
      ensure normal gastrulation.
AB  - To study the role of keratin filaments in Xenopus development, fertilized eggs
      were injected with anti-keratin monoclonal antibodies. The anti-keratin
      monoclonal antibodies AE1 and AE3 induce abnormal gastrulation; in the most
      severely affected embryos gastrulation fails completely. In contrast, embryos
      injected with the anti-keratin antibody 1h5 develop normally. Immunocytochemical
      data indicate that injected 1h5 binds to the dense superficial keratin filament
      system of the embryo but not to the deeper keratin filament networks of
      ectodermal and subectodermal cells. Injected AE1 and AE3 do not bind to the
      superficial keratin system but appear to interact preferentially with the deep
      keratin filament systems of the embryo. We conclude that the superficial keratin
      filament system is not involved in the process of gastrulation per se but may
      protect the embryo from mechanical damage. On the other hand, our results suggest
      that the integrity of the deeper keratin filament systems is required for the
      mechanical integration of the morphogenetic movements that underlie gastrulation
      in Xenopus.

PMID- 1382298
TI  - Escherichia coli MutY protein has both N-glycosylase and apurinic/apyrimidinic
      endonuclease activities on A.C and A.G mispairs.
AB  - In Escherichia coli the mutY (or micA)-dependent DNA mismatch repair pathway can
      convert A degrees G and A degrees C mismatches to C.G and G.C base pairs,
      respectively, through a short repair-tract mechanism. The MutY protein has been
      purified to near homogeneity from an E. coli overproducer strain. Purified MutY
      has been shown to contain both N-glycosylase and 3' apurinic/apyrimidinic (AP)
      endonuclease activities. The N-glycosylase removes the mispaired adenines of A
      degrees G and A degrees C mismatches, and the AP endonuclease acts on the first
      phosphodiester bond 3' to the AP sites. The N-glycosylase and the nicking
      (combined N-glycosylase and AP endonuclease) activities copurified through
      multiple chromatographic steps without a change in relative specific activities.
      Furthermore, both N-glycosylase and AP endonuclease activities can be recovered
      by renaturation of a single polypeptide band from an SDS/polyacrylamide gel.
      Renaturation required the presence of iron and sulfide. These findings suggest
      that the MutY protein, like endonuclease III, is an iron-sulfur protein. DNA
      fragments with A degrees C mismatches were 20-fold less active than DNA with A
      degrees G mispairs as a substrate for purified MutY.

PMID- 1382300
TI  - Cytokine involvement in the regulation of sleep.

PMID- 1382299
TI  - Calcium-dependent increase in tyrosine kinase activity stimulated by angiotensin
      II.
AB  - The cellular effects of numerous hormones and neurotransmitters, including the
      vasoactive agents angiotensin II (AngII) and [Arg8]vasopressin, are mediated in
      part by protein-serine threonine kinases activated by increase of cytosolic Ca2+
      concentration. In this study, we have tested the ability of Ca(2+)-mobilizing
      agents to activate cellular tyrosine kinases. Treatment of intact GN4 liver
      epithelial cells with AngII rapidly (less than or equal to 15 sec) increased
      tyrosine kinase activity measured either in unfractionated cell lysates or in
      anti-phosphotyrosine immune complexes from detergent-solubilized cells. Increased
      phosphorylation of the exogenous substrate poly(Glu80Tyr20) (3- to 4-fold over
      control) by immunoprecipitated kinases closely paralleled the time- and dose
      dependence of the appearance of tyrosine phosphoproteins in intact cells. This
      effect of AngII was mimicked by thapsigargin, a Ca(2+)-elevating tumor promoter.
      The ability of AngII, but not epidermal growth factor, to increase tyrosine
      kinase activity was blocked in cells loaded with the Ca2+ chelator bis-(O
      aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid. Dephosphorylation of
      immunoprecipitated proteins by tyrosine phosphatase treatment was accompanied by
      a 60-70% loss in in vitro kinase activity, suggesting that the AngII-sensitive
      kinase(s) are activated by phosphorylation in intact cells. These findings
      demonstrate a link between two widely occurring signaling pathways, the tyrosine
      kinases and the Ca2+ second-messenger system, and suggest the possible
      involvement of Ca(2+)-activated tyrosine kinases in the endocrine actions of
      AngII and [Arg8]vasopressin.

PMID- 1382301
TI  - Studies on antigen specifity of immunoreactive arabinogalactan proteins extracted
      from Baptisia tinctoria and Echinacea purpurea.
AB  - In a series of experiments the cross-reactivity of antibodies raised against
      arabinogalactan proteins from Baptisia tinctoria and Echinacea purpurea was
      studied in order to prove the antigen specificity of the extracted
      glycoproteins/polysaccharides. Using the antigen-antibody reaction in a
      competitive ELISA it was evident that antibodies against glycoproteins from
      Baptisia tinctoria were specific because none of the other antigens like those
      from Echinacea purpurea, Thuja occidentalis, arabinogalactan from larch, LPS from
      E. coli 055:B5, and from Salmonella typhimurium were able to inhibit the antigen
      antibody reaction. The same results were obtained from ELISA experiments with
      Echinacea purpurea. From these studies it was concluded that the antigenic
      regions of immunoreactive proteins from both medicinal plants show structural
      differences.

PMID- 1382302
TI  - [The body--a symbol of the unconscious?].
AB  - Based on Lacan's differentiation between the real, the imaginary and the symbolic
      it is shown that Moser's connection between psychoanalysis and therapy is almost
      exclusively concentrated on the body in the sphere of the imaginary. According to
      Bittner, when the body is regarded symbolically, it represents a highly emotional
      "transcription" of the unconscious.

PMID- 1382303
TI  - Ionic currents in cochlear hair cells.

PMID- 1382304
TI  - [Growth factors and hematopoiesis. Physiopathology and clinical applications].
AB  - Recently biotechnologic progress has, through the technique of the recombinant
      DNA, allowed a low cost production of large amount of several growth factors.
      Such a large availability has made possible to either carry out deeper
      investigations on the physiopathology of the hemopoietic regulation and perform
      new therapeutic approaches under different pathologic conditions. The most
      interesting acquisition concerning the biology of hemopoiesis to which such
      investigations have addressed us is the inadequacy of the protocols adopted till
      now. Such protocols considered only a simple vision of an elective action of a
      given growth factor during an exact maturation period of a determined cell
      colony. On the contrary, it was possible to point out a close network of inter
      relationship among the different factors, which sometime impedes a clear
      distinction for each single factor, between actions of competence and progression
      in the cell maturation phenomena. However, the present uncertainty pertaining to
      the regulation of hemopoiesis has not impede the performance of clinical trials
      with positive findings in several pathologic conditions. The administration of
      recombinant erythropoietin has for example allowed to intervene in a resolutive
      way on the anemia in uremic subjects, and seems giving satisfactory results also
      in subjects with non renal origin anemic conditions. Satisfactory results were
      also obtained through the use of the Granulocyte-Macrophage CSF and of the
      Granulocyte-CSF, which by preventing neutropenia have allowed the performance of
      more adequate chemotherapeutic protocols in neoplastic subjects. New interesting
      perspectives are now coming for the use of Interleukin-3 in the treatment of the
      aplastic anaemia.

PMID- 1382305
TI  - [Rush immunotherapy in bronchial asthma].

PMID- 1382307
TI  - Our patients face recovery with confidence.

PMID- 1382306
TI  - [Hepatitis C infection and liver cell carcinoma].
AB  - Epidemiological data disclose that the incidence of hepatocellular carcinoma
      (HCC) is increasing world-wide, whereas the number of cases positive for HBV
      marker has remained almost stable, at least in Japan. Data from Europe show
      positivity of antibodies against hepatitis C virus (anti-HCV) in 72% of HBsAg
      negative cases with HCC and in 28% of patients positive for HBsAg. Nearly 90% of
      HBsAg negative patients with HCC showed a histology of cirrhosis or chronic
      active hepatitis in the noncancerous liver. Almost every third patient had a
      history of blood transfusion. These results suggest an increasing incidence of
      HCV - associated HCC's, as it already has been shown for patients suffering from
      chronic HBV infection.

PMID- 1382308
TI  - Nursing the thoracotomy patient.

PMID- 1382309
TI  - When your patient needs back surgery.

PMID- 1382310
TI  - [Vidarabine phosphate in the treatment of active chronic hepatitis B. A confirmed
      hope].

PMID- 1382311
TI  - MAP kinases: charting the regulatory pathways.

PMID- 1382312
TI  - Modulation of the dimerization of a transcriptional antiterminator protein by
      phosphorylation.
AB  - The transcriptional antiterminator protein BglG inhibits transcription
      termination of the bgl operon in Escherichia coli when it is in the
      nonphosphorylated state. The BglG protein is now shown to exist in two
      configurations, an active, dimeric nonphosphorylated form and an inactive,
      monomeric phosphorylated form. The migration of BglG on native polyacrylamide
      gels was consistent with it existing as a dimer when nonphosphorylated and as a
      monomer when phosphorylated. Only the nonphosphorylated dimer was found to bind
      to the target RNA. When the dimerization domain of the lambda repressor was
      replaced with BglG, the resulting chimera behaved like an intact lambda repressor
      in its ability to repress lambda gene expression, which suggests that BglG
      dimerizes in vivo. Repression by the lambda-BglG hybrid was significantly reduced
      by BglF, the BglG kinase, an effect that was relieved by conditions that
      stimulate dephosphorylation of BglG by BglF. These results suggest that the
      phosphorylation and the dephosphorylation of BglG regulate its activity by
      controlling its dimeric state.

PMID- 1382313
TI  - Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth
      factor.
AB  - Coronary collateral vessels reduce damage to ischemic myocardium after coronary
      obstruction. Factors that stimulate collateral formation are expected to have
      ameliorating effects on myocardial infarction. In a canine experimental
      myocardial infarct model, intracoronary injection of basic fibroblast growth
      factor (bFGF) improved cardiac systolic function and reduced infarct size.
      Treatment with bFGF increased the number of arterioles and capillaries in the
      infarct. Thus, the angiogenic action of bFGF might lead to a reduction in infarct
      size. The application of bFGF might bring about a therapeutic modality for the
      salvage of infarcted myocardium.

PMID- 1382314
TI  - Control by asparagine residues of calcium permeability and magnesium blockade in
      the NMDA receptor.
AB  - The N-methyl-D-aspartate (NMDA) receptor forms a cation-selective channel with a
      high calcium permeability and sensitivity to channel block by extracellular
      magnesium. These properties, which are believed to be important for the induction
      of long-term changes in synaptic strength, are imparted by asparagine residues in
      a putative channel-forming segment of the protein, transmembrane 2 (TM2). In the
      NR1 subunit, replacement of this asparagine by a glutamine residue decreases
      calcium permeability of the channel and slightly reduces magnesium block. The
      same substitution in NR2 subunits strongly reduces magnesium block and increases
      the magnesium permeability but barely affects calcium permeability. These
      asparagines are in a position homologous to the site in the TM2 region (Q/R site)
      of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that
      is occupied by either glutamine (Q) or arginine (R) and that controls divalent
      cation permeability of the AMPA receptor channel. Hence AMPA and NMDA receptor
      channels contain common structural motifs in their TM2 segments that are
      responsible for some of their ion selectivity and conductance properties.

PMID- 1382315
TI  - Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein
      kinase.
AB  - The double-stranded RNA-dependent protein kinase (dsRNA-PK) is thought to be a
      key mediator of the antiviral and antiproliferative effects of interferons
      (IFNs). Studies examining the physiological function of the kinase suggest that
      it participates in cell growth and differentiation by regulating protein
      synthesis. Autophosphorylation and consequent activation of dsRNA-PK in vitro and
      in vivo result in phosphorylation of the alpha subunit of eukaryotic initiation
      factor-2 (eIF-2) and inhibition of protein synthesis. Expression of a
      functionally defective mutant of human dsRNA-PK in NIH 3T3 cells resulted in
      malignant transformation, suggesting that dsRNA-PK may function as a suppressor
      of cell proliferation and tumorigenesis.

PMID- 1382316
TI  - Regulation by ATP and ADP of CFTR chloride channels that contain mutant
      nucleotide-binding domains.
AB  - Regulation of the cystic fibrosis transmembrane conductance regulator (CFTR)
      chloride channel is unusual in that phosphorylated channels require cytosolic
      adenosine triphosphate (ATP) to open. The CFTR contains two regions predicted to
      be nucleotide-binding domains (NBDs); site-directed mutations in each NBD have
      now been shown to alter the relation between ATP concentration and channel
      activity, which indicates that ATP stimulates the channel by direct interaction
      with both NBDs. The two NBDs are not, however, functionally equivalent: adenosine
      diphosphate (ADP) competitively inhibited the channel by interacting with NBD2
      but not by interacting with NBD1. Four cystic fibrosis-associated mutations in
      the NBDs reduced absolute chloride channel activity, and one mutation also
      decreased the potency with which ATP stimulates channel activity. Dysfunction of
      ATP-dependent stimulation through the NBDs may be the basis for defective CFTR
      chloride channel activity in some cystic fibrosis patients.

PMID- 1382317
TI  - Prostatic specific antigen in prostate cancer.

PMID- 1382318
TI  - Screening for prostate cancer: PSA blood test, rectal examination, and
      ultrasound.

PMID- 1382319
TI  - [Effects of mepartricin on the growth of hypertrophic prostatic tissue in primary
      culture. Creation of the experimental model and preliminary results].
AB  - The aim of this study was to standardise a method for the in vitro culture of
      hypertrophic prostatic tissue, to assay the morphological type of isolated cells,
      to evaluate the degree of proliferation and to identify their differentiated
      iter. In addition, the effects of mepartricina on growth was also studied
      obtaining preliminary results. Of a total of 40 biopsies used in this experiment,
      30 were placed directly in culture using Freshney's method, whereas the remaining
      10 were used in a method involving the primary culture of the dispersed cells
      obtained from enzymatically disaggregated tissue. In vitro proliferation was
      analysed using optic microscopy, histological and histochemical techniques, and a
      scanning electron microscope. Cellular kinetics were also studied by
      bromodeoxyuridine marking. Using these tests it was found that it is possible to
      obtain the development and growth in this form of culture of fibroblastic-type
      colonies of epithelial origin characterised by different morphologies and growth
      curves. In addition, cells from the epithelioid colonies are characterised by a
      high level of proliferative activity and a low degree of differentiation.
      Mepartricina appears, on the other hand, to inhibit the in vitro growth of
      hypertrophic prostatic tissue.

PMID- 1382320
TI  - [Role of mepartricin in the metabolism of intraprostatic epoxisterols. Clinico
      therapeutic implications].

PMID- 1382321
TI  - [Effect of mepartricin treatment on the concentrations of the receptors for the
      insulin-like growth factor-I (IGF-I) in human adenomatous tissue].

PMID- 1382322
TI  - [Epidermal growth factor binding and steroid receptor content in human benign
      prostatic hypertrophy].

PMID- 1382323
TI  - Pharmacological manipulation of peripheral resistance during distal vascular
      reconstruction.
AB  - A randomised placebo-controlled trial was conducted to investigate the effects of
      iloprost, a stable prostacyclin analogue, on peripheral resistance, during femoro
      crural arterial bypass. 3000 ng of iloprost, infused into the graft, produced an
      immediate drop in peripheral resistance by a mean (range) of 43% (4-80%; p less
      than 0.01, Wilcoxon). Decreased peripheral resistance persisted to 20 minutes.
      Graft flow during the same period increased by 59.8% (-7 to 294%; p less than
      0.01) and this increase persisted after the operation. Iloprost produces an
      immediate decrease in peripheral resistance associated with a prolonged increase
      in graft blood flow. This may reduce graft failure in the early postoperative
      period.

PMID- 1382324
TI  - Dimethylnitrosamine (DMN)-induced IL-1 beta, TNF-alpha, and IL-6 inflammatory
      cytokine expression.
AB  - Altered immune functions have been demonstrated in mice following exposure to
      dimethylnitrosamine (DMN). In particular, changes in cell-mediated immune
      responses resulted from chronic DMN exposure in vivo. Since cytokines are potent
      immunoregulatory peptides, experiments were performed to determine whether DMN
      exposure results in the induction of serum-borne inflammatory cytokines. Animals
      were exposed to either vehicle (PBS) or DMN (5.0 mg/kg) every 24 hr for 14 days.
      Serum and liver samples were obtained from individual mice at 0, 1, 2, 3, 6, 12,
      and 24 hr following the first exposure, with additional samples collected every
      24 hr preceding the daily DMN exposure. Sera were then analyzed for IL-1 beta, IL
      3, IL-6, CSF-1, GM-CSF, and TNF-alpha activities using either biological or
      immunological assays. In addition, liver total cellular RNA was probed for the
      induction of IL-1 beta transcripts using the solution hybridization/RNase
      protection assay. IL-1 beta, IL-6, and TNF-alpha serum activities were observed
      within 2 hr of DMN exposure and returned to vehicle control levels by 3 days even
      though DMN exposure was maintained. Chronic expression of cytokine activity
      (after 72 hr) was only observed for GM-CSF. A rapid induction of IL-1 beta
      transcripts (within 1 hr) in both vehicle and DMN-treated animals was observed by
      solution hybridization. However, by 3 hr postexposure, transcript levels
      decreased in the vehicle-treated animals while remaining elevated in the DMN
      treated animals for 6 hr. These results demonstrated that DMN exposure in vivo
      induced: (1) the expression of serum-borne cytokine activities, and (2) IL-1 beta
      transcription in liver tissue.

PMID- 1382325
TI  - Neutralization of myotoxic phospholipases A2 from the venom of the snake Bothrops
      asper by monoclonal antibodies.
AB  - The neutralization of two myotoxic phospholipases A2 from the venom of Bothrops
      asper, myotoxins I and II, by two murine monoclonal antibodies is reported. The
      monoclonal antibodies, MAb-3 and Mab-4, recognize different epitopes of the
      toxin. Both antibodies completely neutralized myotoxic activity of myotoxin I and
      crude venom. MAb-3 also completely neutralized myotoxic activity of myotoxin II,
      a lysine-49 phospholipase A2 isoform, whereas MAb-4 neutralized this toxin only
      partially. MAb-3 neutralized myotoxin II at a molar ratio of 1:1, showing a
      higher efficiency than affinity-purified polyclonal antibodies. A dissociation of
      myotoxic and enzymatic activities of myotoxin I was observed with both monoclonal
      antibodies.

PMID- 1382326
TI  - Alzheimer's disease and beta A4: getting to the core of the problem?

PMID- 1382327
TI  - Neuronal Ca2+: getting it up and keeping it up.

PMID- 1382328
TI  - Finding new genes in the nervous system by cDNA analysis.
AB  - There are several methods to isolate cDNAs that do not require prior biochemical
      characterization of their protein products, including isolation of new members of
      particular protein families based on sequences of known members, selection of
      specific clones by differential screening, and shotgun analysis of a particular
      cDNA population. This third approach will produce a huge catalogue of cDNA
      sequences and anatomical data that will be useful to investigators with diverse
      interests. Recent methodological advances allow cDNAs to be isolated and
      sequenced rapidly. These methods, coupled with fast and reliable techniques for
      in situ hybridization histochemistry, should permit cDNA catalogues to be
      assembled efficiently.

PMID- 1382329
TI  - The nerve growth factor family of receptors.
AB  - The neurotrophins, of which nerve growth factor (NGF) is the best known example,
      support the survival and differentiation of chick embryo sensory neurons at
      extremely low concentrations, 10(-12) M or less. These same neurons display two
      different classes of neurotrophin receptors with dissociation constants of 10(
      11) M and 10(-9) M, respectively, implying that only low occupancy of the higher
      affinity receptor is required to mediate the biological actions of the
      neurotrophins. Two structurally unrelated receptors have now been characterized
      for NGF, and one of them, p75NGFR, serves as a receptor for all the known
      neurotrophins. This is the receptor with a dissociation constant of 10(-9) M. The
      second NGF receptor is a member of the trk family of tyrosine kinase receptors,
      p140trkA. Other members, p145trkB and p145trkC, are receptors for brain-derived
      neurtrophic factor (BDNF) and neurotrophin-4 (NT-4) and neurotrophin-3 (NT-3),
      respectively, when assayed in fibroblasts. The specificity of neurotrophin
      binding to these receptors appears to be much higher in neurons than in the non
      neuronal cells. The receptor p140trkA has many of the properties of the higher
      affinity class of NGF receptors, and is able to mediate survival and
      differentiation of the PC12 cell line, and cell growth and transformation in
      fibroblast cells. On the other hand, expression of p75NGFR in several types of
      cells displaying p140trkA induces a component of higher affinity NGF binding not
      seen in its absence. Since it is unlikely that p75NGFR and p140trkA interact at
      the level of the receptors, the crosstalk between receptors probably occurs
      through their signal transduction mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382330
TI  - Vive la difference!
AB  - Hormonal effects are increasingly recognized as important influences on neuronal
      function and, ultimately, on animal behavior. Such 'higher' behavioral effects
      are well studied, particularly in relation to sexually dimorphic behaviors. Yet,
      somewhat surprisingly, a significant proportion of more basic neuroscience
      research papers fail to specify the sex of the subjects used. In this brief
      article Karen Berkley argues that knowledge of, and controlling for, the sex of
      research animals is important. In addition, if females are used, their
      reproductive-cycle status could provide a deliberate strategy to investigate the
      effects of gonadal steroid hormones on biological functions.

PMID- 1382331
TI  - Protein kinase C modulation of NMDA currents: an important link for LTP
      induction.
AB  - A brief high frequency tetanic stimulation of afferent fibers induces a long-term
      potentiation (LTP) of synaptic transmission, which is manifested by an increase
      in the size of the synaptic response elicited by low frequency stimulation of the
      same synapse. LTP persists for several hours in vitro and up to several weeks in
      vivo, and is at present the most extensively studied form of activity-dependent
      synaptic plasticity. This article focuses on the relationship between two key
      elements in the induction of LTP--the N-methyl-D-aspartate (NMDA) subtype of
      glutamate receptor and the Ca(2+)-phospholipid-dependent protein kinase C (PKC).
      In view of several recent findings that describe a direct positive modulation of
      NMDA currents by PKC, we suggest that PKC activity may, in fact, determine the
      threshold of LTP induction. Enhanced kinase activity may underlie the central
      role of the NMDA receptor--channel complex in neuronal plasticity.

PMID- 1382332
TI  - Is the brain too complicated for simple replacement therapy?

PMID- 1382333
TI  - Individual differences in the cognitive and neurobiological consequences of
      normal aging.
AB  - Defining the neural basis of age-related cognitive dysfunction is a major goal of
      current research on aging. Compelling evidence from laboratory animals and humans
      indicates that aging does not inevitably lead to cognitive decline. Conducting
      neurobiological investigations in subjects that have previously undergone
      behavioral characterization has therefore emerged as a promising strategy for
      identifying those alterations in brain structure and function that are
      specifically associated with age-related cognitive impairment.

PMID- 1382334
TI  - Voltage-gated ion channels in Schwann cells and glia.
AB  - In the past decade, particularly its last half, it has become clear that the
      satellite cells of the nervous system (oligodendrocytes and astrocytes in the
      CNS, Schwann cells in the PNS) are liberally endowed with a vast array of voltage
      gated ion channels. These original observations of the various channel types have
      been followed by the elucidation in considerable detail of the
      electrophysiological characteristics of the channels. Virtually all of the types
      of voltage-gated channel found in neurons have now also been found in the various
      populations of satellite cells. In spite of this, the intriguing questions
      concerning the physiological function of these channels remain to be fully
      elucidated.

PMID- 1382335
TI  - Distribution and functional significance of the P-type, voltage-dependent Ca2+
      channels in the mammalian central nervous system.
AB  - In addition to the three types of voltage-dependent calcium channels presently
      recognized in the CNS, the L-, the T- and the N-types, a fourth distinct type
      known as the P-type channel has recently been described. This channel, initially
      recognized in Purkinje cells (and thus the name), is not blocked by
      dihydropyridines or by omega-conotoxin (GVIA), but is blocked by native funnel
      web spider venom and by a polyamine (FTX) extracted from such venom. In addition,
      a synthetic polyamine (sFTX) has been produced that also specifically blocks P
      channels in brain slices and at the neuromuscular junction, and blocks
      presynaptic Ca2+ currents in other vertebrate and invertebrate forms, as well as
      channels expressed in Xenopus oocytes following CNS mRNA injections. Using sFTX
      to form an affinity gel, a protein was isolated and reconstituted into lipid
      bilayers where it manifests single-channel properties that are
      electrophysiologically and pharmacologically similar to those of the native P
      channels. Rabbits immunized with the isolated protein produced a polyclonal
      antibody that gave a positive western blot with the purified P-channel protein
      and generated a reaction product at specific sites in the CNS that agree with the
      physiological distribution of P-channel activity.

PMID- 1382336
TI  - Structural basis of voltage-gated K+ channel pharmacology.
AB  - Major advances have been made in understanding the domains and amino acid
      sidechains important for the function of voltage-gated K+ channels, by combining
      recombinant DNA techniques with pharmacological and electrophysiological
      approaches. As explained in this review by Olaf Pongs, the results of these
      experiments have enabled description of a detailed model of the K+ channel pore
      structure and provide an exciting picture of how open-channel blockers occlude
      the pore of K+ channels. Since the pore is a highly conserved structure among
      voltage-gated K+ channels, there are only limited possibilities for open K+
      channel blockers to distinguish between the many distinct voltage-gated K+
      channels, which have diverse kinetic and conductance properties.

PMID- 1382337
TI  - [Immunologic disorders in patients with idiopathic subretinal neovascular
      membrane].
AB  - The authors analyze the results of comprehensive clinical and immunologic
      examinations of 52 patients with this condition (SNVM) in its active and inactive
      phases, angiographically confirmed, aged 19 to 46; 32 of these were women
      (61.5%), 20 (38.4%) men. A complex of immunologic methods was employed to reveal
      the etiology of the condition and the immune status of SNMV patients. The origin
      of the condition was identified in 44.2% of patients; it was toxoplasmic in 19.2,
      autoimmune in 15.4, tuberculous in 7.7, and mixed toxoplasmic and tuberculous in
      1.9% of cases. T lymphocyte functional activity was inhibited in 37.5% of
      patients with the exudative hemorrhagic phase of SNMV and in 16.7% of those in
      the cicatrization phase. Changes in the humoral immunity presenting as
      gammapathies were detected in 34% of patients, those manifesting by
      hyperconcentrations of circulating immune complexes in 66.7%, and of
      cryoglobulins in 37.8% of patients. Krypton laser coagulation was employed in
      multiple-modality treatment of patients with SNMV. The remissions persisted for 3
      5 years.

PMID- 1382338
TI  - Distinctive pattern of infection and replication of HIV1 strains in blood-derived
      macrophages.
AB  - The macrophage-tropic virus HIV1-PAR, isolated from cerebrospinal fluid of HIV1
      seropositive man, induced cytopathic effect accompanied by different magnitude of
      the virus production in blood-derived macrophages (BDM) obtained from different
      donors. HIV1-PAR-specific RNA was detected by in situ hybridization in 15 and 66%
      of BDM producing low and high levels of virus, respectively. In contrast with
      HIV1-PAR, infection of BDM with two laboratory strains adapted to T-cell lines,
      HIV1-LAV prototype and HIV1-NDK, a Zairian virus that is highly cytopathic for T
      lymphocytes, resulted in a low production of HIV1 p24gag in culture fluid.
      Expression of HIV1-LAV and HIV1-NDK RNA was detected by in situ hybridization in
      a maximum of 1% of macrophages. Only HIV1-NDK, and not HIV1-LAV, induced
      ultrastructural alterations in BDM. In contrast with a striking difference in the
      production of macrophage-tropic and T-lymphotropic viruses, no significant
      differences were found in the proportion of macrophages containing
      retrotranscribed genomes of HIV1-. HIV1 DNA was detected by in situ hybridization
      in 93, 100, and 80% of macrophages infected with HIV1-PAR, HIV1-LAV, and HIV1
      NDK, respectively. A higher level of HIV1 DNA was detected by polymerase chain
      reaction in the BDM infected with HIV1-PAR than in that infected with HIV1-LAV
      and HIV1-NDK. The results indicate that both macrophage-tropic as well as T
      lymphotropic viruses can enter and retrotranscribe their genomes in a vast
      majority of macrophages.

PMID- 1382339
TI  - Amino acid residues of the human immunodeficiency virus type I gp120 critical for
      the binding of rat and human neutralizing antibodies that block the gp120-sCD4
      interaction.
AB  - We have characterized the discontinuous epitopes recognized by two rat and three
      human neutralizing monoclonal antibodies (mAb) by examining the effect of single
      amino acid changes in conserved residues of gp120 on mAb recognition. A human mAb
      derived from an infected individual, 448D, and two rat mAbs, 39.13g and 39.3b,
      respectively, derived by immunization with native recombinant gp120, recognize
      similar epitopes. Recognition of the envelope glycoproteins by these mAbs was
      affected by changes in gp120 amino acid residues 88, 113, 117, 257, 368, or 370.
      The gp120 amino acids 257, 368, and 370 have previously been reported to be
      important for CD4 binding, which is consistent with the ability of these mAbs to
      block the gp120-CD4 interaction. Residues 88, 113, and 117 are not thought to be
      important for CD4 binding, suggesting that the antibody epitopes overlap, but are
      distinct from, the CD4 binding region. We also found that some alterations in
      gp120 residues 88, 117, 368, or 421 reduced the ability of polyclonal sera from
      HIV-1-infected individuals to inhibit the interaction of the mutant gp120
      glycoproteins with soluble CD4. Thus, changes in the HIV-1 gp120 glycoprotein
      that minimally affect the receptor binding may allow escape from neutralizing
      antibodies directed against the CD4 binding region.

PMID- 1382340
TI  - Viral spliced RNA are produced, encapsidated and reverse transcribed during in
      vivo woodchuck hepatitis virus infection.
AB  - By the use of reverse transcription followed by polymerase chain reaction (RT
      PCR), we have identified one shorter than full-length, pregenomic viral RNA
      species in liver samples of woodchucks chronically infected with the woodchuck
      hepatitis virus (WHV). The spliced WHV RNA of about 2.4 kb in length was cloned
      and partially sequenced. The splicing donor and acceptor sites of this novel RNA
      are located, respectively, 130 nucleotides downstream of the ATG initiation codon
      of the core gene and 21 nucleotides upstream of the initiation codon of the pre
      S2 surface gene. The splicing event generates a new core-polymerase fusion
      protein and removes the terminal protein domain and the spacer region of the
      polymerase gene. A nucleotide probe specific for the splice junction was used
      following RT-PCR, to further confirm the existence of this spliced RNA in the
      liver of seven WHV-infected woodchucks. Deleted viral DNA molecules corresponding
      to the 2.4 kb spliced RNA were also detected in the liver and, to a lesser
      extent, in the serum of infected woodchucks, suggesting that this spliced RNA can
      be encapsidated and reverse-transcribed during the course of natural WHV
      infection.

PMID- 1382341
TI  - Prevention of the spread of HIV-1 infection with nonnucleoside reverse
      transcriptase inhibitors.
AB  - Certain bisheteroarylpiperazines (BHAPs) directly inhibit the replication of
      human immunodeficiency virus type 1 (HIV-1) and block the spread of infection to
      susceptible populations of cells. At a 1 microM concentration three analogs, U
      87201, U-88204, and U-89674, inhibited the replication of HIV-1 in MT-2 cells by
      83, 100, and 93%, respectively. At the same concentration, U-88204 completely
      inhibited replication of primary HIV-1 isolates in peripheral blood mononuclear
      cells. Replication of 3'-azido-2',3'-dideoxythymidine (AZT)-resistant strains of
      HIV-1 was also inhibited by U-88204. When MT-2 cells that were lytically infected
      with HIV-1 were mixed with uninfected MT-2 cells, U-88204 provided complete
      protection to the uninfected cells. Integrated proviral DNA sequences were not
      detected by the polymerase chain reaction technique in this culture after 15 days
      in the presence of drug. The resultant healthy cell culture was subsequently
      maintained without drug with no evidence of latent proviral DNA. Serial passage
      of a laboratory strain and a primary isolate of HIV-1 in cell culture in the
      presence of increasing concentrations of U-88204 yielded virus populations which
      were at least 100-fold resistant to the drug. These resistant viruses also showed
      cross-resistance to the pyridinone class of nonnucleoside inhibitors but were
      sensitive to AZT. Analysis of the nucleotide sequence of resistant viruses
      revealed mutations at conserved regions of the reverse transcriptase (RT) gene.
      The results presented here suggest the therapeutic potential of U-88204 in the
      combination therapy for HIV-1 infection.

PMID- 1382342
TI  - Antibody response to human papovavirus JC (JCV) and simian virus 40 (SV40) T
      antigens in SV40 T antigen-transgenic mice.
AB  - Human papovavirus JC (JCV) and simian virus 40 (SV40) genomes share approximately
      69% homology; and there is antigenic cross-reactivity between JCV and SV40 tumor
      or T antigens. In order to determine whether a selective immune response to JCV T
      antigen could be demonstrated, transgenic mice (SV11+) that express SV40 T
      antigen in the choroid plexus and are partially tolerant to antigenic
      determinants on SV40 T antigen were immunized with SV40 or JCV T antigens and
      their antibody responses were analyzed. The results show that SV11+ mice
      responded as well as their nontransgenic litter mates to JCV T antigen.
      Monoclonal antibodies were derived from hybridomas generated from immunized mice
      which reacted specifically with epitopes in the amino and carboxy terminal halves
      on JCV T antigen. These studies show that transgenic mice expressing SV40 T
      antigen are capable of responding to determinants not shared between JCV and SV40
      T antigen.

PMID- 1382343
TI  - The transmembrane domain of influenza A M2 protein forms amantadine-sensitive
      proton channels in planar lipid bilayers.
AB  - In a direct test of the hypothesis that the M2 coat protein of influenza A can
      function as a proton translocator, we incorporated a synthetic peptide containing
      its putative transmembrane domain into voltage-clamped planar lipid bilayers. We
      observed single proton-selective ion channels with a conductance of approximately
      10 pS at a pH of 2.3, consistent with the association of several monomers around
      a central water-filled pore. The channels were reversibly blocked by the anti
      influenza drug amantadine. These experiments imply a central role for M2 protein
      in virus replication and assembly and may explain the mechanism of action of
      amantadine. Analogous proteins may have a similar function in other viruses, and
      these may be susceptible to similar antiviral agents.

PMID- 1382344
TI  - Herpesvirus saimiri has a gene specifying a homologue of the cellular membrane
      glycoprotein CD59.
AB  - Herpesvirus saimiri (HSV) is a T-lymphotropic tumor virus that causes fulminant
      lymphomas and leukemias in various New World primates other than its natural
      host, the squirrel monkey (Saimiri sciureus). In the course of completing the
      nucleotide sequence of its genome, we identified an open reading frame of 363
      nucleotides, designated HVS-15, that has no detectable homology to any other
      viral sequences to date. HVS-15 encodes a 121-amino-acid protein which shows
      significant similarities to human CD59, a phosphatidyl-inositol-glycan-anchored
      glycoprotein involved in T-cell activation and restriction of complement-mediated
      lysis. The predicted HVS-15 gene product is more similar to human CD59 than to
      the related murine Ly-6 antigens. A nucleotide sequence identity of 64% was found
      between HVS-15 and the CD59 reading frame, and a 48% identity exists between the
      corresponding protein sequences. The comparison of the amino acid sequences
      revealed a number of conserved structural features such as a similar pattern of
      hydrophobic termini and an identical cysteine skeleton.

PMID- 1382345
TI  - HPV-1 L1 protein expressed in cos cells displays conformational epitopes found on
      intact virions.
AB  - Seven polyclonal and monoclonal antibodies were characterized for their ability
      to react specifically with either conformational or nonconformational epitopes of
      the HPV-1 virion. Using these antibodies, it was shown that the HPV-1 L1 protein
      (when expressed by an SV40 vector in cos cells) displayed conformational epitopes
      characteristic of intact viral particles. In addition, the L1 capsid protein was
      translocated normally into cell nuclei, was of appropriate size (57 kDa), and
      could be isolated in native form by immunoprecipitation techniques. Most
      importantly, the screening of expressed papillomavirus capsid proteins for
      reactivity with conformation-dependent antibodies represents a new, general
      methodology for ensuring that such proteins will be suitable for use in vaccine
      development or in the serologic detection/typing of human papillomavirus
      infections.

PMID- 1382346
TI  - The innervation of the great saphenous vein: an immunohistochemical study with
      special regard to regulatory peptides.
AB  - The human great saphenous vein is often used in by-pass surgery. In spite of its
      importance little is known about the neuronal regulation and innervation of this
      vessel. On the other hand, therapeutic phlebectomy of the saphenous vein provides
      a good basis for investigations on the nervous supply of human veins. In former
      studies the human great saphenous vein has been proved to be a richly innervated
      portion of the low pressure vascular system. We studied the innervation of the
      proximal femoral saphenous vein by immunohistochemical methods and with special
      regard to regulatory neuropeptides. A peptidergic innervation mainly localized
      along the vasa vasorum and associated with immunoreactivity of substance P and
      CGRP was found which yields evidence for a mechanosensory innervation of this
      vascular segment.

PMID- 1382347
TI  - The expression of insulin-like growth factor binding proteins is tissue specific
      during human fetal life and early infancy.
AB  - The insulin-like growth factors (IGFs) are bound to multiple IGF binding proteins
      (IGFBPs) that are present both in the circulation and in extracellular fluids.
      There are at least six different IGFBP species that have been fully characterized
      in terms of molecular structure and amino acid sequence. The tissue distribution
      and local production of these proteins as well as the regulation of IGFBP
      production in different tissues have not been elucidated. We have studied the
      distribution of multiple IGFBP species in protein extracts from human kidney,
      skeletal muscle, lung, liver and brain by ligand blotting employing [125I]IGF-2
      as the radiolabeled hormone. Five distinct IGFBP species with a respective
      molecular weight of 43, 38, 34, 30 and 20 kDa were detected on the ligand blots
      in tissues from human fetuses and infants (23 weeks of gestation till 24 months
      of postnatal age). The 34 kDa species and a 30-32 kDa IGFBP species were
      predominant in brain, whereas a 30 kDa IGFBP species was mainly detected in
      skeletal muscle. Immunoblotting experiments using an anti IGFBP-2 antiserum
      showed that the 34 kDa IGFBP species from human brain was presumably related to
      IGFBP-2. We conclude that IGFBPs are differentially expressed in different
      tissues throughout human fetal life and early infancy. Local production or
      accumulation of the different IGFBPs could modulate IGF action at a local level
      or alternatively have differential functions during development.

PMID- 1382348
TI  - Histochemistry of the porcine pilosebaceous unit.
AB  - The present study describes lectin and immunoreactivity in the pilosebaceous unit
      of porcine skin. Complex carbohydrates of mucin and biantennary Man/Gluc types
      were distributed among hair follicle epithelia (hair root sheaths, cuticula,
      shaft, and shaft matrix). Sebaceous glands expressed biantennary Man/Gluc
      carbohydrates and GalNAc residues. The expression of simple-type and epidermis
      like keratins was confirmed by immunohistochemistry with monoclonal antibodies.
      Filaggrin-positive cells were found in the keratinizing zone of Henle's layer in
      anagen follicles. The innermost layer of the outer hair root sheath was stained
      with antibodies against the epidermal growth factor-receptor, keratin 10 and Ki67
      antigen. The differences to humans were remarkably small.

PMID- 1382349
TI  - DNA cytochemistry in polytene chromosomes: electron contrasting agents for the
      ultrastructural detection of chromatin DNA after alkaline hydrolysis/methylation
      acetylation.
AB  - Salivary glands from Chironomus tentans larvae were fixed in glutaraldehyde and
      either subjected to alkaline hydrolysis followed by methylation-acetylation, or
      dehydrated without these treatments as controls. Ultrathin sections from Durcupan
      embedded samples were contrasted by means of uranyl acetate, ruthenium red,
      indium trichloride, or the complex indium (III)-hematoxylin. Electron microscopic
      observations revealed a general contrasting pattern in control sections, while
      after the hydrolytic and blocking procedure only chromatin from polytene
      chromosomes appeared selectively contrasted. The nucleolus, Balbiani ring
      granules and puff materials showed weak or no electron opacity. After toluidine
      blue staining of semithin sections, an orthochromatic blue colour was found in
      chromatin bands from treated samples. These results indicate that alkaline
      hydrolysis/methylation-acetylation followed by contrasting with cationic heavy
      compounds is a valuable procedure to visualize chromatin DNA in polytene
      chromosomes.

PMID- 1382351
TI  - Patterns of cytokeratins and vimentin in guinea pig and mouse eye tissue:
      evidence for regional variations in intermediate filament expression in limbal
      epithelium.
AB  - The anatomical distribution of different individual cytokeratin polypeptides and
      of vimentin was investigated by means of immunofluorescence with 41 monoclonal
      antibodies in guinea pig and mouse eyes. Simple epithelial type cytokeratins 7,
      8, 18, and 19 selectively decorated conjunctival goblet cell clusters in mouse
      specimens and a continuous superficial cell layer of the corresponding part of
      guinea pig conjunctiva. A changed pattern of squamous epithelial type
      cytokeratins was found in the limbal region of the guinea pig eye as compared to
      the corneal epithelium. Cytokertains 3 and 17, which stained the entire corneal
      epithelium, were not detected, whereas cytokeratin 4, 5 and 13 were expressed. A
      focal vimentin and cytokeratin coexpression in the limbus of guinea pig is
      interpreted as indicating corneal stem cells. Similar patterns of expressions
      were found in the mouse ocular surface. In both species, a cytokeratin 4 staining
      of basal conjunctival epithelial cells could be detected. The neuroectodermally
      derived epithelia of the eye such as the retinal pigment epithelium and the
      ciliary body epithelia expressed solely the cytokeratin pair 8/18.

PMID- 1382350
TI  - Influence of inorganic salts on the staining reaction of eosinophil leukocyte
      granules by anionic dyes.
AB  - The use of salts as competing agents in staining solutions allows to evaluate to
      what extent ionic interactions take place between microscopical substrates and
      cationic or anionic dyes. We have employed this method to study the staining
      reaction of horse eosinophil leucocyte granules by the anionic dyes nuclear fast
      red, naphthol yellow S, eosin Y, indigocarmin, acid fuchsin, alizarin red S,
      orange G, and Evans blue in the presence of NaCl (from 0.015 to 2 mol/l).
      Different values of "minimal electrolyte concentration" (the least amount of salt
      which reduces the staining intensity) were found for these dyes. Comparative
      observations using ammonium sulphate as competing salt showed that it is less
      effective than NaCl. Staining of eosinophil granules by anionic dyes could be not
      suppressed at 2 mol/l NaCl, which indicates that in addition to electrostatic
      forces, other non-ionic interactions are also responsible for some staining
      reaction of these acidophilic structures.

PMID- 1382352
TI  - Immunoelectron microscopic localization of microsomal alanine aminopeptidase.
AB  - The localization of microsomal alanine aminopeptidase was investigated in the rat
      kidney. Resin embedding failed to demonstrate the localization of the enzyme by
      immunogold labelling. Using a cryo-ultramicrotomy method the enzyme could be
      detected on the luminal side of the brush border membrane of proximal tubular
      cells and to a lesser degree in their mitochondria. Furthermore, vesicular
      structures labelled with gold were found in the cytoplasma in the apical region
      of these cells.

PMID- 1382353
TI  - Characterization of secretory cell glycoconjugates in the alimentary tract of the
      ruin lizard (Podarcis sicula campestris De Betta) by means of lectin
      histochemistry.
AB  - Secretory cell glycoconjugates of the alimentary canal of the ruin lizard
      (Podarcis sicula campestris De Betta) were characterized by traditional staining
      methods and by lectin histochemistry. The goblet cells of the upper esophagus
      produced sialo- and sulfomucins, while those of the lower esophagus mainly
      contained sulfomucins. Lectin histochemistry demonstrated the presence of N
      acetyl-D-glucosamine and terminal sialic acid. The epithelial mucous cells lining
      the surface of the stomach and the gastric pits contained neutral glycoproteins
      with glycosidic residues of N-acetyl-D-galactosamine, D-glucose, D-mannose, D
      galactose, and N-acetyl-D-glucosamine. The mucous cells of the gastric glands
      produced neutral glycoproteins that contained stable class-III mucosubstances, as
      revealed by Paradoxical Con A staining, with terminal residues of L-fucose and D
      galactose. They can be similar to the true neck cells of the gastric pits of
      other vertebrates. The goblet cells of the small intestine produced acidic
      glycoproteins with glycosidic residues of N-acetyl-D-glucosamine, sulfated esters
      on internal residues and terminal sialic acid. In the large intestine, there is a
      predominance of sulfated mucosubstances with D-galactose, N-acetyl-D-glucosamine,
      and N-acetyl-D-galactosamine. The microheterogeneity of mucins of the digestive
      tract, as proved by lectin histochemistry, is probably connected to their
      different functions.

PMID- 1382354
TI  - The rib perichondrium. An anatomical study in sheep of a tissue used as
      transplant in the treatment of hyaline-cartilage defects.
AB  - Perichondrial tissue is of great importance as a transplant for the repair of
      hyaline-cartilage defects of synovial joints because of its potential to produce
      hyaline-like cartilage. The histological and histochemical character and fiber
      orientation of rib perichondrial grafts prior to a transplantation procedure for
      the repair of full-thickness hyaline-cartilage defects is analyzed in a sheep
      model. Compared to other descriptions of the rib perichondrium of other different
      species and humans, the perichondrial architecture of different origins
      demonstrates the same histological, histochemical character and fiber
      orientation. The three different layers of this tissue are: the outer fibrous
      layer, the central part called proliferation zone and the inner part towards the
      underlying rib called transition zone. The fibrous layer demonstrates a wave-like
      extracellular configuration and contains a few fibrocytes. The proliferation zone
      is only a few cell rows thick and contains single cells with an oval shape and
      longitudinal fibrocyte-like nucleus. Because of the potential of these cells to
      produce cartilage this layer is called proliferation or cambium layer. The
      transition zone contains more oval-shaped cells with rounded nuclei and
      demonstrates a more chondrocytic character. Some cells lie in groups of 2 and
      more cells like in chondrons. The extracellular matrix shows an increasing stain
      towards the rib cartilage indicating new cartilage production. The fiber
      orientation is longitudinal in the fibrous part and vertical in the transition
      zone. Between these layers, fibers deviate from the longitudinal to the vertical
      orientation corresponding to the light-microscopically visible proliferation
      zone.

PMID- 1382355
TI  - Fine structure of the dorsal lingual epithelium of the Japanese monkey Macaca
      fuscata fuscata.
AB  - Filiform papillae, which were densely distributed all over the dorsal surface of
      the lingual body, were crown-shaped, with a central, circular area that sloped in
      the anterior direction and several branches that surrounded it in a semicircle
      from the back of the central area. Dome-shaped, fungiform papillae were scattered
      among these filiform papillae. At the posterior end of the lingual body, there
      were four circumvallate papillae. Prominent microridges and elevated
      intercellular borders were widely distributed in the central area of the filiform
      papillae and the interpapillar region. On the surface of the branches of the
      filiform papillae, microridges were rarely seen. On the surface of the fungiform
      papillae, indistinct microridges were observed. Histologically, the dorsal
      lingual epithelium revealed three different regions: the epithelium on the
      anterior side of the filiform papillae, the epithelium on the posterior side of
      the filiform papillae and the interpapillar epithelium. Whereas the basal and
      suprabasal cells are similar throughout, differences characterize the
      intermediate and surface layers. Keratohyalin granules appear predominantly in
      the intermediate layer in the epithelium on the anterior side of filiform
      papillae. In the epithelium on the posterior side of the filiform papillae, no
      keratohyalin granules occur and, instead, tonofibrils are prominent. The cells
      become significantly flattened. In the interpapillar epithelium, no keratohyalin
      granules are visible, and the tonofilaments occupy almost the entire cytoplasm of
      most cells in the intermediate and surface layers. The cells are larger in volume
      in these layers.

PMID- 1382356
TI  - [Development of resistance of herpes simplex virus to antivirus drugs in vitro].
AB  - Resistant variants of HSV-1 wt strain to ACV, CC, DHPG and PFA can be selected
      after several passages in drug-containing cultures. The degree of resistance of
      different variants varied and emerged at different times. The combination of
      antiviral agents can delay and even prevent the emergence of drug-resistant
      variants. At the same time, the concentration, dose and, therefore, toxicity of
      the antiviral agents can also be reduced. So, it is a feasible method for
      treating resistant HSV infections. Cross-sensitivity tests showed that ACVr
      variants are resistant to ACV, DHPG and PFA, but sensitive to CC; PFAr variants
      are sensitive to ACV, CC and DHPG; CCr variants are sensitive to ACV and DHPG,
      but resistant to PFA; DHPGr variants are sensitive to ACV, CC and PFA. These
      results suggest that the study of cross-sensitivity of HSV strains in vitro
      provide information which will aid the design of suitable therapy for drug
      resistant HSV infections.

PMID- 1382357
TI  - Myocardial force interval relationships: influence of external sodium and
      calcium, muscle length, muscle diameter and stimulation frequency.
AB  - Several inotropic interventions were studied in thin papillary muscles under
      dynamic conditions. The effects on mechanical restitution and postextrasystolic
      potentiation were analysed. The decay of postextrasystolic potentiation was taken
      as a measure of recirculation fraction of activator calcium. The mechanical
      restitution curve had a plateau phase on its rising phase which was abolished in
      low extracellular sodium but pronounced in increased extracellular calcium. The
      recirculation fraction (RF) in control was 0.35 +/- 0.03; lowering the
      extracellular sodium by 20% increased the RF to 0.46 +/- 0.04 (n = 10). A
      reduction of sodium by 40% increased the RF to 0.57 +/- 0.04, whereas increasing
      extracellular calcium to 4 mM gave an RF of 0.48 +/- 0.05 (n = 10 in all cases).
      There was no significant effect on RF of changing basic stimulation frequency or
      muscle preparation length. These findings support RF as a good index of
      myocardial contractility. Furthermore, at muscle diameters above 0.65 mm the RF
      was found to be reduced, suggesting this diameter as critical for muscle
      function. Also, postextrasystolic potentiation in relation to preceding steady
      state contraction was markedly increased at these diameters. In conclusion, this
      study shows that RF is independent of stimulation frequency and muscle length,
      and that it is increased when calcium extrusion by the sodium/calcium exchange is
      reduced. Furthermore, RF is critically dependent upon the diameter of the
      preparation and mechanical restitution is changed by altered extracellular sodium
      concentration.

PMID- 1382358
TI  - Effects of calcium release from the sarcoplasmic reticulum on intramembrane
      charge movement in skeletal muscle.

PMID- 1382359
TI  - nACh receptor-activity modulating intracellular Ca2+ (RAMIC); its finding,
      properties and roles.

PMID- 1382360
TI  - Effect of free radicals on excitation-contraction coupling in isolated rat and
      guinea pig ventricular myocytes.
AB  - Using the model of isolated myocytes, we have investigated under current- and/or
      voltage-clamp conditions: (i) the time-course of H2O2-induced changes in the
      action potentials and the contractility. (ii) the effect of pharmacological tools
      such as ryanodine, TTX and nifedipine on H2O2-induced changes; (iii) the effect
      H2O2 on ionic currents underlying the changes in APD; and (iv) the effect of
      deferoxamine on H2O2-induced changes.

PMID- 1382361
TI  - Action of vasoconstrictor hormones and calcium entry modulators on electrical
      activity and intracellular calcium of smooth muscle cells.

PMID- 1382362
TI  - Excitation-contraction coupling in canine tracheal smooth muscle cells.

PMID- 1382363
TI  - Role of guanylate cyclase activation in the smooth muscle actions of
      dihydropyridines.

PMID- 1382364
TI  - Effects on Ca2+ uptake of monoclonal antibodies raised against canine cardiac
      phospholamban and their correlation with epitopic location.

PMID- 1382365
TI  - Potassium channel activation in vascular smooth muscle.
AB  - 1. Numerous compounds and changes in physical state functions shift the membrane
      potential of vascular smooth muscle to more negative values. The consequence is a
      vasodilatation because Ca2+ channels are closed. K+ channel opening frequently
      causes the hyperpolarization. 2. Acidification of the blood substitute solution
      and a fall in O2 partial pressure dilate arterial vessels. Acidosis is associated
      with a rise in K+ permeability and a simultaneous fall in Na+ permeability.
      Prostacyclin has a 20-30% share, and EDHF a 70-80% share, in hypoxic
      vasodilatation. Experiments with iloprost (PGI2 analogue) confirmed the K+
      channel opening properties of this drug. A voltage-dependent K+ channel and a
      Ca(2+)-activated K+ channel, via the influence of cA-PK or cG-PK, are responsible
      for the hyperpolarization with iloprost and with oxygen deficiency. 3.
      Cicletanine and ajoene cause a concentration-dependent membrane hyperpolarization
      and are potent vasodilators. A cicletanine concentration, which is attained by
      the dosage given to patients, is sufficient to produce these effects. Ajoene
      exerts a hyperpolarizing and vasodilating influence even in a concentration which
      may occur in the extracellular space by the administration of a single garlic
      clove. 4. The stationary activation curve 'developed force vs. membrane
      potential' satisfactorily explains the effects of K+ channel openers. The tight
      electromechanical coupling expressed by this curve comprises a 50% vasorelaxation
      for a 2.5 mV hyperpolarization. In the linear part of the curve, the coupling
      ratio is 5.1 mV/g. 5. In the vascular smooth muscle, vasorelaxation can be evoked
      by membrane hyperpolarization which is linked to a simultaneous increase in K+
      outward current and 42K+ efflux. In the case of substances whose influence is
      solely or partially receptor-mediated, cyclic nucleotides may be involved in
      vasorelaxation. Since cyclic nucleotides also hyperpolarize through an increase
      in K+ conductance, the resulting dilatation often cannot be divided into its
      single components. Therefore, it is sensible not to give the term "K+ channel
      opener" too fine a definition. The term should be applied to all substances and
      changes in physical states which predominantly increase the open probability of
      K+ channels finally via a conformational change in the cell membrane. For
      example, giving an acidic blood substitute solution (acidosis) is an intervention
      opening K+ channels. Which K+ channel and which single channel conductance is
      concerned in a particular case, and which 'mediator' may participate, become
      secondary questions.

PMID- 1382366
TI  - The effect of prednisolone on substance P-induced vascular permeability in mice.
AB  - The effect of prednisolone on the substance P (SP)-induced vascular permeability
      increase in male ddY, WBB6 F1(-)+/+ (control) and WBB6 F1-W/WV (no mast cell in
      skin or internal organs) mice was investigated. 1) SP (1-10,000 pg/site)
      increased vascular permeability in ddY, WBB6 F1(-)+/+ and WBB6 F1-W/WV mice ears.
      2) SP (100 pg/site)-induced vascular permeability was inhibited by prednisolone
      (10 mg/kg) administered intraperitoneally 3 to 12 hours prior to the elicitation
      of the reaction in ddY mice. When dexamethasone at a dose of 1 mg/kg was
      administered intraperitoneally 2 to 24 hours prior to the elicitation of the
      reaction, significant inhibition was observed. When prednisolone was administered
      intraperitoneally 8 hours prior to the elicitation of the reaction, the SP
      induced capillary permeability increase in both ddY and WBB6 F1-W/WV mice was
      clearly inhibited by the drug at doses of 5 and 10 mg/kg. 3) Diphenhydramine (1
      and 10 mg/kg) inhibited SP-induced vascular reaction in ddY mice but not in WBB6
      F1-W/WV mice. 4) Atropine (10 mg/kg) inhibited SP-induced vascular reaction in
      both ddY and WBB6 F1-W/WV mice. But acetylcholine did not cause an increase of
      vascular permeability in ddY and WBB6 F1-W/WV mice ears. 5) Prednisolone (5
      mg/kg) inhibited histamine- and serotonin-induced vascular permeability in ddY
      and WBB6 F1-W/WV mice ears. 6) Prednisolone (5 and 10 mg/kg) inhibited the SP
      induced histamine release from ddY mice peritoneal mast cells. These results
      suggest that the vascular effect of SP is mediated by both mast cell dependent
      (release of histamine from mast cells) and mast cell independent mechanisms.
      Prednisolone inhibits the SP-induced vascular permeability mediated by both
      mechanisms in mice.

PMID- 1382367
TI  - Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from
      human basophils.
AB  - Increased osmotic pressure has been reported to cause non-cytotoxic histamine
      release (HR) from human basophils, as well as a potentiation of HR induced by
      anti-IgE. In this study, the effects of hyperosmolar Na-K-acetate (300-600
      mOsm/kg H2O) on HR was studied in washed human blood cells from newborns, adult
      volunteers and patients with severe atopic dermatitis. These three patient groups
      represented 3 very distinct populations with respect to total plasma IgE content,
      medians were less than 0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml; respectively.
      Increasing osmolarity to 500 mOsm/kg H2O caused little HR in the absence of other
      stimuli, whereas at 600 mOsm/kg H2O a significant increase in spontaneous HR was
      seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE
      receptor, was increased approximately twofold at 500 mOsm/kg H2O. Responses were
      highly correlated to results at 300 mOsm/kg H2O. The use of 600 mOsm/kg H2O
      buffers caused a further increase in most, but not all blood samples. The
      potentiation of IgE-receptor-mediated HR when using hyperosmolar media was
      clearly independent of plasma IgE contents, and did not change the concentration
      response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent
      stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at
      all by increased osmotic pressure. We conclude, that hyperosomolar media
      selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may
      therefore be beneficial in a diagnostic application of washed blood HR assays
      used in allergy diagnosis.

PMID- 1382368
TI  - Modulation of IgE-mediated histamine release from human leukocytes by a new class
      of histamine H2-agonists.
AB  - A new class of phenyl (pyridylalcyl) guanidines, acting as potent histamine H2
      agonists, inhibits IgE-mediated human basophil histamine release in a nanomolar
      range. IC30-level of three substitutes of this group (arpromidine, BUA-75, and
      FRA-19) were found to be 0.02, 0.015 and 0.008 microM. The inhibition appeared
      with a fast onset (plateau after 10 min. preincubation) and claimed its maximum
      (60 +/- 2.9%, 63 +/- 1.8%, and 61 +/- 3.1%, n = 7) with 10 microM of the
      compounds. H2-mediated inhibition was totally blocked by 10 microM famotidine, a
      potent histamine H2-antagonist. The amount of anti-IgE or antigen for the
      initiation of the immunological release influenced the strength of inhibition of
      H2-agonist FRA-19 (p less than 0.05). Combined preincubation of FRA-19 with
      zardaverine, a cAMP-specific phosphodiesterase III/IV inhibitor, produced a
      synergistical inhibitory effect of leukocyte histamine release, which might
      explained by their different sites of action on intracellular cAMP levels. The
      capability of histamine to inhibit its own release is mediated by H2-receptors
      exclusively. New, potent H2-receptor stimulating compounds with positive
      inotropic effects possess additional potent anti-allergic properties.

PMID- 1382370
TI  - Effects of human recombinant IL-1 on d-tubocurarine-induced histamine release
      from isolated rat peritoneal mast cells.
AB  - The relationship between d-tubocurarine (d-Tc) and human recombinant interleukin
      1 (rIL-1) was studied on the histamine-releasing property of isolated rat
      peritoneal mast cells. d-Tc induced histamine release in a dose-dependent manner
      (1 x 10(-4) M-3 x 10(-3) M) from isolated rat mast cells. Human rIL-1 (0.3-10
      ng/ml) potentiated the d-Tc-induced histamine release and shifted the dose
      response curve to left without changing the maximum histamine release by d-Tc.
      The potentiation by human rIL-1 was completely blocked by anti-IL-1-antibody.
      Human rIL-1 neither released histamine nor affected IgE-related histamine release
      in isolated rat peritoneal mast cells. Human recombinant IL-2, IL-3, and tumour
      necrosis factor neither released histamine from isolated rat mast cells nor
      affected d-Tc-induced histamine release. These results suggested that human rIL-1
      might hypersensitize d-Tc receptors distributed on plasma membrane of rat mast
      cells.

PMID- 1382369
TI  - Lymphocyte migration in the mouse. I. Time course of cell accumulation and the
      effect of antigen sensitisation and challenge in a murine model of chronic
      inflammation.
AB  - The effect of time and of antigen sensitisation and challenge on lymphocyte
      migration into a site of chronic inflammation has been examined in the mouse.
      Enhanced lymphocyte migration occurred at sites of chronic inflammation after
      sensitisation and challenge to Bordetella pertussis vaccine (BPV). Biphasic
      migration was observed with time (5 min to 24 h), the initial very rapid but
      transient localisation at the inflamed site being followed by a second slower
      more sustained influx of cells. Increased localisation was also obtained with
      time in the lymphoid tissues and was accompanied by a parallel decrease in the
      number of cells present in the blood. The relative importance of antigen
      sensitisation and challenge for lymphocyte migration to a site of chronic
      inflammation has also been assessed. Lymphocyte migration into the inflamed site
      was partially dependent on the immunological status of the injected lymphocytes,
      but the presence or absence of antigen at the site of inflammation was the major
      factor which determined the degree of migration to the site.

PMID- 1382372
TI  - Influence of CGS 9343B, an inhibitor of calmodulin activity, on histamine release
      from isolated rat mast cells.
AB  - Investigations of calmodulin involvement in cell responses has been complicated
      by the lack of selective calmodulin antagonists. A novel inhibitor, CGS 9343B,
      reportedly without influence on protein kinase C, is used in the present study of
      mast cell responses. The histamine release induced by antigen and compound 48/80
      in the presence of calcium was enhanced by 10-20 microM CGS 9343B and inhibited
      by higher concentrations. Only inhibitory effects on the response to compound
      48/80 in the absence of calcium and to the ionophore A23187 were observed, the
      latter being inhibited by 20 microM CGS 9343B. The influence on responses to
      combinations of the phorbol ester TPA and the ionophore A23187 was more complex,
      giving rise to enhancement at lower and inhibition at higher concentrations of
      CGS 9343B in a manner which depended on the experimental conditions. Unlike
      previously used calmodulin antagonists, CGS 9343B is devoid of detergent effects
      and without serious metabolic interference. The inhibitor seems useful to reveal
      differences in the mechanisms involved in responses to various histamine
      liberators. Our results conform with an inhibition of calmodulin by CGS 9343B but
      are at present inconclusive.

PMID- 1382371
TI  - The roles of calmodulin and protein kinase C in histamine secretion from mast
      cells.
AB  - The effect of a new calmodulin-antagonist, 5-iodo-1-C8, with a high selectivity
      for calmodulin in comparison to protein kinase C, has been investigated on
      histamine secretion from mast cells. It has been found to be much more sensitive
      for the inhibition of histamine secretion than the earlier calmodulin
      antagonists, trifluoperazine and W7. The effect of four inhibitors of protein
      kinase C, viz. staurosporine, K252a, tamoxifen and sphingosine, has also been
      studied on histamine secretion from mast cells. All of them caused dose-dependent
      inhibition of histamine secretion induced by the three secretagogues used:
      antigen, compound 48/80 and the calcium ionophore A23187. K252a was tested
      against histamine release, induced by the stimulation of protein kinase C alone
      with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) or the
      synthetic diacylglycerol, 1-oleoyl-2-acetyl-rac-glycerol (OAG). In both the cases
      K252a caused dose-dependent inhibition of histamine release. Staurosporine was
      also tested against TPA and was found to inhibit the release induced by it.
      Potentiation and inhibition (modulation) of secretagogue-induced histamine
      release by simultaneous protein kinase C stimulation with TPA or OAG have been
      demonstrated before. The potentiation and inhibition are shown to be antagonized
      by staurosporine. The observations point to the involvement of both calmodulin
      and protein kinase C in the histamine secretion process from mast cells.

PMID- 1382373
TI  - Inhibition of IgE-mediated histamine release from human peripheral leukocytes by
      selective phosphodiesterase inhibitors.
AB  - Several phosphodiesterase (PDE) inhibitors with the capacity to inhibit the PDE
      IV isoenzyme produce dose-dependent inhibition of IgE-mediated histamine release
      (HR) from human peripheral leukocytes in vitro. Inhibition reached a maximum
      after 20 min of preincubation (IC30: 6-30 microM, IC50: 30-80 microM). Motapizone
      -a potent inhibitor of the isoenzyme PDE III--was much less effective, thus
      giving indirect evidence that PDE IV plays a predominant role in the control of
      cAMP cleavage in human basophils. The inhibiting effect of PDE-III/IV-selective
      compounds on IgE-mediated HR did not exceed the action of PDE-IV-selective
      inhibitors. The inhibition of anti-IgE-induced HR by zardaverine (a PDE-III/IV
      inhibiting compound) was synergistically enhanced in the combined presence of
      forskolin or the recently synthesized histamine H2-agonist FRA 19).

PMID- 1382374
TI  - Inhibition of histamine release from human granulocytes by ions of the rare earth
      elements lanthanum and cerium.
AB  - The influence of the ATPase inhibitors, lanthanum or cerium, on histamine release
      in basophils and mast cells was studied. Both compounds inhibited IgE- or A23187
      induced histamine release. To exclude a general inhibition of calcium-dependent
      reactions in the cell, we tested the influence of these compounds on phagocytosis
      and superoxide production of neutrophil granulocytes. Phagocytosis of Candida
      albicans was inhibited partially, superoxide generation, measured by the INT test
      after stimulation with zymosan or aggregated gamma globulin, was not affected.
      Because of the inhibitory effect of lanthanum or cerium compounds on membrane
      ATPase and immunological function of epidermal Langerhans cells we propose that
      these compounds may be used in the treatment of atopic eczema, where both
      histamine-releasing mast cells and IgE-bearing Langerhans cell play a
      pathogenetically important role.

PMID- 1382375
TI  - A 5-lipoxygenase inhibitor, FR110302, suppresses airway hyperresponsiveness and
      lung eosinophilia induced by Sephadex particles in rats.
AB  - To study the role of chemical mediators in airway hyperresponsiveness and
      simultaneous eosinophilia, we examined effects of a potent 5-lipoxygenase
      inhibitor FR110302 and those of prednisolone, indomethacin, platelet-activating
      factor (PAF) antagonist (RP-59227) and leukotriene C4 (LTC4) antagonist (ONO
      1078) on airway hyperresponsiveness and lung eosinophilia induced by Sephadex
      particles. Sephadex G200 particles (2.5 mg/kg) were injected intravenously to
      rats and 3 days later the airway hyperresponsiveness to acetylcholine (ACh) and
      the eosinophilia in the bronchoalveolar lavage (BAL) fluids were observed.
      FR110302 (10 mg/kg b.i.d.p.o.) significantly suppressed both of these indicators
      of asthma. The amounts of immunoreactive LTB4,C4 (i-LTB4, C4) in the BAL fluid
      were measured by radioimmunoassay. The amounts of i-LTB4,C4 in the FR110302
      treated rats were significantly less compared with that in the Sephadex-injected
      controls. Prednisolone completely inhibited the airway hyperresponsiveness. PAF
      antagonist and LTC4 antagonist partially inhibited the airway
      hyperresponsiveness, and indomethacin had no effect. The results indicate that 5
      lipoxygenase products play important roles in the Sephadex-induced airway
      hyperresponsiveness and lung eosinophilia in rats.

PMID- 1382376
TI  - Effect of compounds from Mandevilla velutina on bradykinin-mediated contractile
      and relaxant responses of the isolated guinea pig trachea.
AB  - This study examines the action of three putative functional bradykinin (BK)
      antagonists isolated from Mandevilla velutina on BK and other agonist-induced
      contraction or relaxation responses in intact or in epithelium-denuded strips of
      tracheal muscle from guinea pigs. Compound MV 8612 (8 and 16 microM) and MV 8610
      (12 and 24 microM) caused a graded rightward displacement of BK dose-response
      curves in the isolated guinea pig trachea (dose ratio 2- to 4-fold). Compound MV
      8608 (28 microM) had a small effect on BK contractile responses. At high
      concentrations, compound MV 8612 (24 microM) caused a slight but significant
      depression of the BK-induced maximal responses. These pharmacological actions
      appear to be quite selective towards BK, since within the same concentration
      range these compounds failed to interfere with the sensitivities to prostaglandin
      F2 alpha, carbachol and histamine. However, these compounds significantly
      enhanced maximal responses to the latter two agonists, an action that was not
      influenced by indomethacin. In addition, MV 8612 and MV 8608 (16 and 56 microM)
      significantly potentiated BK-mediated epithelium-dependent relaxation responses
      in preparations precontracted with carbachol. These compounds also significantly
      potentiated isoprenaline but not theophylline-relaxant responses, an action that
      seems to occur independently of the generation of cyclooxygenase products of
      arachidonic acid pathway. These results further extend our previous studies and
      indicate that some of the M. velutina compounds exert a weak though selective
      antagonistic action against BK-induced contractile responses of the isolated
      epithelium-denuded guinea pig tracheal smooth muscle and potentiate BK-induced
      relaxations in tissues with intact epithelium precontracted with
      carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382377
TI  - Inhibition by calcium antagonists of shape changes induced in vitro by pro
      inflammatory mediators in venous endothelial cells.
AB  - The changes in shape of endothelial cells (ECs) lining rat inferior venae cavae
      in response to exposure in vitro to platelet activating factor (PAF, 5 x 10(-7)
      M), or 5-hydroxytryptamine creatinine sulphate (5HT, 3 x 10(-5) M), or calcium
      ionophore A23187 (1 x 10(-5) M), or cytochalasin B (CB, 1 x 10(-5) M) were
      assessed using an immunofluorescence technique and semi-automated image analysis.
      Most of these shape changes were prevented by lowering intracellular Ca2+ levels
      in several ways. Thus, pre-treatment with ryanodine (1 x 10(-6) M), verapamil HCl
      (2 x 10(-5) M), indomethacin (1 x 10(-4) M), isoprenaline sulphate (2 x 10(-6) M)
      or dibutyryladenosine 3'5' cyclic monophosphate (DbcAMP, 1 x 10(-5) M)
      significantly reduced the effects of PAF, 5HT and A23187. Pre-treatment of ECs
      with 8(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate HCl (TMB-8, 1 x 10(-5) M)
      or the nominal absence of Ca2+ in the extracellular medium prevented the effects
      of PAF and 5HT, but not those of A23187. The responses to 5HT were also reduced
      by cyproheptadine HCl (3 x 10(-6) M). However, only the absence of extracellular
      Ca2+ reduced the effects of CB. The calmodulin inhibitor N-(6-aminohexyl)-5
      chloro-1-naphthalene sulphonamide HCl (W7, 1 x 10(-5) M) and the protein kinase C
      inhibitor 1-(5-isoquinolinyl sulphanyl)-2-methylpiperazine 2HCl (H7, 1 x 10(-5)
      M) were without effect against all the above agonists, but H7 and verapamil
      prevented EC shape changes induced by phorbol myristate acetate (PMA, 1 x 10(-6)
      M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382378
TI  - Serine-protease inhibitors modulate nitric oxide-synthase activity of alveolar
      macrophages.
AB  - Immunostimulated peritoneal macrophages of mice and rat have been demonstrated to
      produce L-arginine-derived nitrogen oxides. This metabolic pathway has also
      recently been found in rat alveolar macrophages and is suggested to play a
      certain role in lung injury. In vitro nitrite production from alveolar
      macrophages stimulated in vitro with lipopolysaccharide and recombinant
      interferon-gamma was inhibited by the addition of the irreversible serine
      protease inhibitors, N-tosyl-L-phenylalanine chloromethyl-ketone (3 x 10(-7)-3 x
      10(-4) M) and N-tosyl-L-lysine chloromethyl-ketone (3 x 10(-7)-3 x 10(-4) M) in a
      concentration-dependent manner. Two reversible inhibitors, N-alpha-p-tosyl-L
      arginine methyl ester hydrochloride and benzoyltyrosine ethyl ester, were also
      effective but to a lesser extent. These antiproteases provide an opportunity to
      study the modulating influence on this recently discovered inflammatory pathway
      in alveolar phagocytic cells.

PMID- 1382379
TI  - PLA2-induced oedema in rat skin and histamine release in rat mast cells. Evidence
      for involvement of lysophospholipids in the mechanism of action.
AB  - Injection of phospholipase A2 (PLA2) in the rat skin produced a significant rise
      in oedema, which was inhibited by the simultaneous coinjection of aristolochic
      acid (100 micrograms), mepacrine (100 micrograms) and p-bromophenacyl bromide (10
      micrograms). Indomethacin, nordihydroguaiaretic acid and WEB 2086 were without
      inhibitory effect on this model, whereas dexamethasone (5 mg/kg, p.o.) and
      coinjection of chlorpheniramine (20 micrograms) inhibited the oedema formation by
      more than 60%. Dose-dependent histamine release by rat peritoneal cells was
      induced by PLA2 and by lysophosphatidylserine and this effect could be
      antagonized by aristolochic acid and mepacrine. Apomorphine, previously reported
      to be an antagonist at lysophospholipid receptors, was able to inhibit the
      histamine release by mast cells as well as the oedema formation in rat skin.
      Taken all together, these results suggest that lysophospholipids, produced by the
      action of PLA2, are the mediators for the histamine release in rat peritoneal
      cells and could play an important role in the early oedema development in rat
      skin after PLA2 administration.

PMID- 1382380
TI  - Participation of alpha 2-macroglobulin in counter-irritation.
AB  - The participation of corticosteroids and alpha 2-macroglobulin (alpha 2-M) in
      counter-irritation (CI) induced by carrageenin was studied. We observed that CI
      could be produced when the second stimulus was done after 24 h, at which time
      glucocorticoids had already returned to their basal levels but alpha 2-M levels
      were maximum. When the level of alpha 2-M decreased (48 h) the counter-irritatory
      effect was not observed. As the synthesis of this protein is corticosteroid
      dependent, we did not observe CI in adrenalectomized rats. However, when
      adrenalectomy was done 20 h after the first stimulus, allowing the synthesis of
      large amounts of alpha 2-M, the carrageenin stimulus again produced CI.
      Furthermore, adrenalectomized rats treated with aprotinin, a kallikrein
      inhibitor, after the first carrageenin stimulus, showed a reduction of the
      response to the second carrageenin stimulus. These observations demonstrated that
      corticosterone was not directly responsible for this inhibitory effect.
      Nevertheless, the anti-inflammatory factors involved in CI were, in fact,
      corticosteroid-dependent and alpha 2-M was probably one of the main factors.

PMID- 1382381
TI  - Biochemical changes in arthritic rats under the influence of vitamin E.
AB  - Two phases of adjuvant arthritis, acute phase (4 days after adjuvant inoculation)
      and chronic phase (21 and 29 days after adjuvant inoculation) were studied in
      male rats. The effect of administration of vitamin E in a daily oral dose of 147
      mg/kg body wt. for one week against these phases of arthritis were demonstrated
      before and after adjuvant inoculation. Results showed that administration of the
      vitamin before and after adjuvant inoculation increased the lowered serum-SH
      group in arthritic rats so that their level was restored to pre-arthritic values
      especially in chronic treated group. Meanwhile, these treatments produced no
      change in the increased level of blood GSH or erythrocyte SOD activity of
      arthritic rats. The results showed also that administration of vitamin E before
      adjuvant inoculation increased significantly the level of alpha 2-M while it did
      not alter the increased serum Cp in acute phase. However, administration of the
      vitamin after adjuvant inoculation failed to exert any change in these
      parameters. In the meantime, these treatments tended to increase the lowered A/G
      of arthritic rats in different phases especially in acute one. These observations
      suggest that antioxidants such as vitamin E may be beneficial for arthritis.

PMID- 1382382
TI  - Lobenzarit disodium (CCA) inhibits the proliferation of human endothelial cells
      and the activity of DNA polymerase alpha.
AB  - N-(2)-Carboxyphenyl-4-chloroanthranilic acid disodium [Lobenzarit disodium (CCA)]
      is widely used for the treatment of patients with RA in Japan; however, the
      pharmacological mechanism of the compound is still unclear. In this report, the
      effect of CCA on the proliferation and DNA synthesis of endothelial cells was
      examined. CCA inhibited DNA synthesis in endothelial cells at a rather lower
      concentration than that in fibroblasts and HeLa cells. The DNA polymerase alpha
      activity was inhibited by CCA at a lower concentration than E. coli DNA
      polymerase I and avian myeloblastosis virus reverse transcriptase. Thus, CCA is a
      potent inhibitor of DNA polymerase alpha and this inhibitory effect could cause
      the inhibition of endothelial cell proliferation, which may be related to the
      therapeutic and pharmacological mechanisms of CCA.

PMID- 1382383
TI  - [Measurement of serum PSA values by DELFIA PSA and its clinical significance on
      diagnosis and follow-up of prostate cancer patients].
AB  - Serum prostate specific antigen (PSA) values detected by DELFIA PSA were
      evaluated for usefulness in the diagnosis and follow-up of patients with prostate
      cancer. The system is time-resolved fluoroimmunoassay using europium as a tracer,
      which has a detectable range of 0.10-500 ng/ml with a small sample volume (25
      microliters) and reliable quality control data. Furthermore, serum PSA values
      detected by the assay were equivocal to those detected by Tandem-R PSA. From the
      mean +3 S.D. of serum PSA values obtained on 227 normal males, 1.98 ng/ml was
      decided as an upper normal level. Serum PSA values in benign prostatic
      hyperplasia (BPH) (n = 69) and prostate cancer (n = 86) patients were
      statistically higher than those in normal males. However, when 1.98 ng/ml was
      used as a cut-off value, the false positive rate in BPH cases elevated up to 80%.
      Therefore, in the differential diagnosis of prostate cancer and BPH, we recommend
      11.7 ng/ml (mean + S.D. in BPH cases) as a cut-off value, in which sensitivity is
      72.1%, 88.4% are true negative in BPH, and efficacy is 79.4%. Serially determined
      serum PSA values in following up the patients with prostate cancer were confirmed
      to be highly effective for diagnosing recurrence and evaluating treatment
      responses. These findings suggest that DELFIA PSA is a useful tool for
      determination of serum PSA values.

PMID- 1382384
TI  - Faster slide photography.

PMID- 1382385
TI  - Prevention of life-threatening arrhythmias by pharmacologic stimulation of the
      muscarinic receptors with oxotremorine.
AB  - The potential antiarrhythmic efficacy of pharmacologic parasympathetic activation
      is still controversial. This study assessed the antiarrhythmic effect of saline
      solution (n = 9) and of the muscarinic agonist oxotremorine (1.5 micrograms/kg
      administered intravenously) (n = 17) in a feline animal model in which malignant
      arrhythmias were reproducibly elicited by the combination of acute myocardial
      ischemia and left stellate ganglion stimulation. Although saline solution had no
      effect, oxotremorine significantly decreased heart rate, blood pressure, the
      incidence of ventricular fibrillation from 47% to 0% (p = 0.004), and the
      incidence of malignant arrhythmias (either ventricular tachycardia or ventricular
      fibrillation) from 88% to 12% (p less than 0.001). When reduction in heart rate
      was prevented by means of atrial pacing (n = 15), the incidence of malignant
      arrhythmias was still significantly reduced from 87% to 27% (p = 0.001).
      Arrhythmias were also graded as follows: 0 = no premature ventricular
      contractions; 1 = 1 to 10 premature ventricular contractions; 2 = 11 to 50
      premature ventricular contractions; 3 = ventricular tachycardia; 4 = ventricular
      fibrillation. Arrhythmia severity was 3.29 +/- 0.16 (SEM) in the control trials
      and was reduced to 0.76 +/- 0.26 (p less than 0.001) by oxotremorine and to 1.53
      +/- 0.34 by oxotremorine and pacing (p = 0.002). Therefore a muscarinic agonist
      can significantly reduce malignant arrhythmias during acute myocardial ischemia
      and may represent a novel approach to the prevention of sudden cardiac death.

PMID- 1382386
TI  - Influence of lidocaine on human muscle sympathetic nerve activity during
      programmed electrical stimulation and ventricular tachycardia.
AB  - Lidocaine directly affects conduction and refractoriness of ventricular
      myocardium, and may also indirectly affect these electrophysiologic properties by
      inhibition of cardiac sympathetic nerve traffic. Both effects may play important
      roles in preventing ventricular arrhythmias in humans. To determine if lidocaine
      has a direct effect on sympathetic nerve activity, the effects of a 100 mg
      lidocaine bolus followed by a 2 mg/min infusion of lidocaine on muscle
      sympathetic nerve activity was assessed in seven patients during programmed
      ventricular stimulation with single extrastimuli (premature ventricular
      contractions [PVCs]) in sinus rhythm, and in seven patients during induced
      hemodynamically stable monomorphic ventricular tachycardia. During single
      extrastimuli, the mean (+/- SEM) area of PVC-associated bursts of sympathetic
      nerve activity was unaffected by lidocaine (1101 +/- 16 units pre-lidocaine
      versus 1075 +/- 19 units following lidocaine; p = 0.30). Likewise, the transient
      decrease in blood pressure with induced PVCs was similar before and after
      lidocaine infusion (p = 0.46). In seven patients with induced monomorphic
      ventricular tachycardia, tachycardia cycle length did not change after the
      lidocaine bolus (393 +/- 18 versus 399 +/- 17 msec; p = 0.34) but increased
      during lidocaine maintenance infusion (428 +/- 17 msec; p = 0.01). After
      induction of ventricular tachycardia, systolic pressure decreased from 150 +/- 6
      to 117 +/- 9 mm Hg at 1 minute of tachycardia, to 109 +/- 6 mm Hg during the
      lidocaine bolus, and rebounded to 126 +/- 8 mm Hg during the lidocaine
      maintenance infusion (p = 0.04, bolus versus infusion).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382387
TI  - The importance of derived 12-lead electrocardiography in the interpretation of
      arrhythmias detected by Holter recording.
AB  - Holter monitoring has been used extensively for the detection, diagnosis, and
      evaluation of therapy for cardiac arrhythmias. The availability of three-channel
      monitors allows for the recording of vectorcardiographic leads X, Y, and Z. One
      method, which was recently described by Dower et al., (J Electrocardiol
      1988;21:5182-7), uses modified vectorcardiographic leads and allows for the
      acquisition of a derived 12-lead ECG of selected rhythm strips during the
      recording. In the present study, we evaluated the usefulness of the derived 12
      lead ECG in the detection of P-wave and ST-segment shifts, assessment of QRST
      changes, and distinction between ventricular ectopic and aberrant
      supraventricular complexes. Our preliminary findings indicate that careful
      analysis of the derived 12-lead ECG provides additional information for a more
      accurate diagnosis of arrhythmias that are detected by the Holter monitor. The
      clinical importance and cost-effectiveness of the derived 12-lead ECG needs
      further evaluation.

PMID- 1382388
TI  - Elevated levels of midtrimester maternal serum alpha-fetoprotein are associated
      with preterm delivery but not with fetal growth retardation.
AB  - OBJECTIVE: Our objective was to determine if the low birth weight associated with
      unexplained elevations of midtrimester maternal serum alpha-fetoprotein levels is
      due to prematurity or to fetal growth retardation. STUDY DESIGN: Rates of preterm
      delivery and fetal growth retardation were analyzed according to incremental
      maternal serum alpha-fetoprotein levels in 5555 women, predominantly white, who
      were screened for neural tube defects (group 1) and 843 women, predominantly
      black, with risk factors for low birth weight (group 2). Statistical methods
      included chi 2, t tests, analysis of variance, and regression analysis. RESULTS:
      In both groups increasing levels of maternal serum alpha-fetoprotein are
      significantly associated with preterm delivery but not with fetal growth
      retardation. The preterm delivery rate increased in each group from 8% at levels
      less than 0.5 multiples of the median to 18.1% (p less than 0.001) at levels
      greater than or equal to 2.5 multiples of the median in group 1 and 28.1% (p =
      0.01) in group 2. CONCLUSIONS: Women with unexplained elevations of maternal
      serum alpha-fetoprotein are at increased risk for preterm delivery but not fetal
      growth retardation. Because of the wide availability of maternal serum alpha
      fetoprotein screening, women at increased risk for preterm delivery can be
      identified in the midtrimester of pregnancy.

PMID- 1382389
TI  - Transient hyperthyroidism and hyperemesis gravidarum: clinical aspects.
AB  - OBJECTIVES: Our objectives were to describe the presentation and course of
      hyperemesis gravidarum with respect to thyroid function and to test the
      hypothesis that patients with biochemical hyperthyroidism differ in clinical
      presentation from euthyroid hyperemesis patients. STUDY DESIGN: Sixty-seven
      patients seen at Los Angeles County Women's Hospital over a 10-month period with
      hyperemesis gravidarum were studied prospectively with respect to thyroid
      function. RESULTS: Forty-four patients (66%) had biochemical hyperthyroidism
      (increased free thyroxine index [n = 39] or suppressed thyroid-stimulating
      hormone [n = 40]) that was self-limited, resolving by 18 weeks' gestation.
      Hyperthyroid patients were more likely than euthyroid patients to have abnormal
      electrolyte levels (23/39 [59%] vs 6/28 [21%] and increased liver enzyme levels
      (23/59 [59%] vs 5/28 [18%], p less than 0.01). The severity of hyperemesis was
      found to vary directly with the degree of hyperthyroidism. CONCLUSIONS:
      Hyperthyroidism is a common, self-limited finding in hyperemesis. The cause of
      the hyperthyroidism may be linked to the cause of hyperemesis itself.

PMID- 1382390
TI  - Overview of current treatment of neuroblastoma.
AB  - Neuroblastoma is the second most common solid tumor in infants and children.
      Improvement of therapy for stage IV patients remains the major goal of research
      in treatment of neuroblastoma. New approaches under study are focused in four
      main areas: (a) phase II studies; (b) mega-therapy procedures; (c) targeted
      therapy; and (d) immunotherapy. Future approaches will be closely linked to
      progress in laboratory investigation and more efficient use of currently
      available drugs. Of all the childhood malignancies, this is the one tumor where
      such an approach is most likely to be effective.

PMID- 1382391
TI  - Ethanol enhances the release of dopamine and serotonin in the nucleus accumbens
      of HAD and LAD lines of rats.
AB  - The effects of intraperitoneal administration of ethanol, 0.5, 1.0, and 2.0 g/kg
      body weight, on the extracellular concentrations of dopamine (DA), serotonin (5
      HT), and their major metabolites were studied in the nucleus accumbens (ACC) of
      alcohol-naive, selectively bred high-alcohol-drinking (HAD) and low-alcohol
      drinking (LAD) lines of rats using the technique of microdialysis. In both lines,
      the extracellular levels of DA were increased following the injection of 1.0 and
      2.0 g of ethanol/kg body weight while only the 2.0-g/kg dose elevated the
      concentration of 5-HT. None of the ethanol doses altered the extracellular levels
      of the major metabolites of DA and 5-HT. Dose-response curves for DA and 5-HT
      release indicated no marked difference in the sensitivity to ethanol between the
      lines. Local perfusion with 60 mM K+ through the microdialysis probe markedly
      enhanced the release of DA and 5-HT in the ACC of both lines; there was a small
      difference between the lines in the amounts of DA, but not 5-HT, released by K(+)
      stimulation. Overall, the results indicate that (1) the ACC DA system is more
      sensitive than the ACC 5-HT system to intraperitoneal ethanol administration in
      both lines and (2) there is no evidence for a relationship between alcohol
      preference and sensitivity of the ACC DA and 5-HT systems to acute
      intraperitoneal ethanol administration.

PMID- 1382392
TI  - Effects of prenatal ethanol exposure on hippocampal ionotropic-quisqualate and
      kainate receptors.
AB  - Previous studies from our laboratories have shown that the consumption of
      moderate quantities of ethanol by rat dams during pregnancy reduces N-methyl-D
      aspartate (NMDA) agonist receptor binding and NMDA-mediated electrophysiological
      responses in the hippocampal formation of adult offspring. We hypothesized that
      prenatal ethanol exposure would produce similar effects on receptor number and
      agonist-mediated responses of two so-called "non-NMDA" subtypes of glutamate
      receptors, the ionotropic-quisqualate (RS)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA)-sensitive and the kainate-sensitive receptors. Sprague
      Dawley rats were fed either a liquid diet containing 3.35% ethanol, an
      isocalorically matched liquid diet, or lab chow ad libitum throughout gestation.
      No significant differences between offspring from these three groups in the
      agonist concentration-response curves for either AMPA-induced or kainate-induced
      depolarization of hippocampal CA1 pyramidal neurons were observed. Furthermore,
      no significant differences in the density of [3H]-AMPA or [3H]-vinylidene kainic
      acid binding sites in any of the apical dendritic field regions of dorsal or
      ventral hippocampal formation were observed between the groups. These results
      indicate that the ionotropic quisqualate and kainate receptors, located in the
      apical dendritic field regions of the principal hippocampal neurons, are not
      affected by the same degree of prenatal ethanol exposure, which is known to
      reduce NMDA receptor binding and function in these same regions.

PMID- 1382393
TI  - Y-chromosome-specific fluorescence (f-body) of poorly decondensed bovine
      spermatozoa.
AB  - An account is given in this paper of a method of identifying the fluorescence
      body (f-body) as a marker of the Y-chromosome. Also covered by this method is
      poor decondensation of spermatozoal nuclei when exposed to action of 1.25% of
      papain, 0.155% of DTE, and 0.025% of DMSO. Quinacrine mustard was used as
      fluorescent stain, its final concentration being 0.0025%. For staining,
      spermatozoa were suspended for 1-5 h. Average f-body frequency accounted for 41.0
      +/- 5.1% in 35 ejaculates from 22 bulls. The overall variation coefficient
      amounted to 12.4% and thus was higher than each of the single values individually
      recorded from six bulls which were involved with three or four ejaculates (3.6
      7.0%). F-bodies could not be detected by the method generally used on human
      spermatozoa. The applicability of the f-body test to quantification of Y
      spermatozoa in experimental separation of androspermatozoa and gynospermatozoa is
      discussed and is demonstrated by an example.

PMID- 1382394
TI  - Dextran absorption during hysteroscopy with Hyskon, and the biodegradation of
      dextran.

PMID- 1382395
TI  - [The efficacy of transcatheter arterial infusion chemotherapy in patients with
      hepatocellular carcinoma].
AB  - The efficacy of transcatheter arterial infusion chemotherapy was examined for
      patients with hepatocellular carcinoma (HCC) between April 1986 and May 1992. We
      investigated the serial serum AFP level in patients with HCC. In 9 of 18
      patients, the AFP level decreased promptly to 70% of the pretreatment level after
      this treatment. In 29 HCC patients with intrahepatic metastasis or portal
      thrombosis, 10 cases survived more than one year. However, only 3 cases survived
      more than two years after treatment. Our results suggest that we should carefully
      select appropriate drugs sensitive to HCC and also give careful consideration to
      the resistance to anti-cancer drugs.

PMID- 1382396
TI  - [Intra-arterial chemotherapy with granulocyte colony-stimulating factor for
      breast cancer before surgical treatment].
AB  - Intra-arterial chemotherapy (IAC) for far advanced breast cancer is now performed
      as a routine adjuvant chemotherapy before surgical treatment. However, the
      following problems remain unsolved; (1) serious adverse reactions such as
      myelosuppression, (2) unsuccessful insertion of catheter into the internal
      thoracic artery, and (3) long waiting-period from IAC to surgical treatment. The
      present studies were conducted to evaluate the utility of a one-route IAC, in
      which the subclavian artery alone is used, and the efficacy of granulocyte colony
      stimulating factor (G-CSF). There was no significant difference in the antitumor
      effect between the patients with two-route IAC, in which both internal thoracic
      artery and subclavian artery are used, and the patients with one-route IAC.
      Administration of G-CSF in combination with IAC reduced both the frequency and
      the severity of IAC-induced side effects. G-CSF administration during IAC was
      more effective than after IAC. G-CSF prevented IAC-induced myelo-suppression
      and/or accelerated recovery from this complication and thus reduced significantly
      the waiting-period before surgical treatment.

PMID- 1382397
TI  - [A case of complete response of locally advanced breast cancer to arterial
      infusion chemotherapy: cannulation through the right femoral artery and combined
      use of G-CSF].
AB  - We reported a case of locally advanced breast cancer who was cannulated into the
      right internal thoracic artery through the right femoral artery by Seldinger's
      method for intra-arterial chemotherapy and obtained good results. In general,
      aggressive chemotherapy is often accompanied by bone marrow suppression
      necessitating discontinuation of chemotherapy. However, this patient recovered
      from this complication by G-CSF. It was suggested that Seldinger's method is
      suitable for locally advanced breast cancer and that G-CSF has an immediate
      effect of bone marrow suppression caused by aggressive chemotherapy.

PMID- 1382398
TI  - [Hyperthermia for cancer with dextran magnetite using tubular implants].
AB  - Dextran magnetite particles (Meito Sangyo Corp.) are an aqueous magnetite zol and
      a nanometer complex consisting of dextran chains surrounding a core of ultrafine
      iron oxide. The tubular implants were made with polyester tube (3 mm diameter, 20
      mm length) filled with DM aqueous zol (29%w/v). The temperature of an agar
      phantom with implants was measured in the inductive field. Heating was effected
      by creating an electromagnetic field with a 7 kW generator operating at 500kHz
      (Yamamoto Vinyter). The temperature was elevated 3.4 degrees at a distance of 5
      mm from the implant at an inductive power of 2.6 kW. An area of 20 x 20 mm was
      heated while changing the power, the number of implants, and their arrangement.
      Selective heating of cancer was considered possible by inductive heating at 500
      kHz and DM implants. Since the DM aqueous zol configuration can be readily
      changed, treatment of various cancers is possible.

PMID- 1382399
TI  - [Role of polymorphonuclear leukocytes (PMN) and active oxygen species in
      hyperthermia--antitumor effect of hyperthermia combined with rhG-CSF].
AB  - We have reported that polymorphonuclear leukocytes (PMN) and active oxygen
      species from PMN may play an important role in the mechanism of the antitumor
      effect of hyperthermia. At this time, we focused our experimental studies on rat
      AH109A carcinoma treated with hyperthermia combined with arterial injection of
      rhG-CSF. Rats with transplantable AH109A carcinoma at the hind leg received
      hyperthermia. These tumors showed mild suppression of further development only by
      hyperthermia. However, when arterial injection of rhG-CSF was applied together
      with hyperthermia, marked suppression of tumor development was observed. Our data
      suggest that hyperthermia combined with rhG-CSF is closely related to the
      generation of free radical-mediated tumor cell killing, and it can be an
      effective treatment for cancer.

PMID- 1382401
TI  - [Transcatheter arterial embolization therapy of metastatic bony tumor in
      hepatocellular carcinoma--a case report].
AB  - Metastatic bony tumor was found in a patient with liver metastasis of
      hepatocellular carcinoma, 5 years and 2 months after hepatectomy. Transcatheter
      arterial embolization therapy via lumbar artery was performed two times, at first
      with 20 mg of doxorubicin. The response was Progressive Disease by CT and bone
      scintigraphy, but recovery of performance status 4 to 2 was achieved in five
      days. In conclusion, transcatheter arterial embolization therapy may be a choice
      of therapy for metastatic bony tumor of hepatocellular carcinoma.

PMID- 1382400
TI  - [Role of polymorphonuclear leukocytes (PMN) and active oxygen species in
      hyperthermia--enhancing effect of G-CSF on superoxide generation from PMN].
AB  - We examined in vitro the effect of G-CSF and temperature on superoxide (O2-)
      generation by Cypridina luciferin analog (CLA) dependent chemiluminescence. PMN
      significantly generated O2- at the concentration of G-CSF 25 ng/ml or more at 37
      degrees C within the range of 0.1 from 1,000 ng/ml. O2- generation from PMN was
      remarkably enhanced, stimulated by opsonized zymosan (OZ) and phorbol myristate
      acetate (PMA), at 41 degrees C as compared with 37 degrees C. O2- generation was
      enhanced with the addition of 25 ng/ml of G-CSF at 41 degrees C as compared to
      without it at 41 degrees C. A significant enhancement of O2- generation from PMN
      was observed at 25 ng/ml G-CSF and 41 degrees C.

PMID- 1382402
TI  - [Pharmacokinetics of the interferon inducer PHL-6 and interferon synthesis in
      target organs under various methods of drug administration].
AB  - The pharmacokinetics of PHL-6 and interferon synthesis dynamic in the target
      organs (tissues) of mice were studied during its and intraperitoneal
      administration. In the experimental setting, there was a direct correlation
      between the interferon production in the murine organs with single PHL-6 and
      distribution of 14C PHL-6. The highest radioactivity with its oral administration
      was detected in the liver and intestine. Interferon was actively synthesized in
      the intestine, liver and serum, showing the levels of 20000, 1024-2048 and 512
      1024 IU/ml, respectively. The prolonged action of the drug was in good agreement
      with the low PHL-6 excretion from the body. It was also shown that almost the
      whole radiation dose 1 (greater than 98%) was excreted with feces and urine after
      single and chronic administrations of uniformly labeled PHL-6 which proved
      important clinical drug use.

PMID- 1382403
TI  - Secretion of lysosomal and digestive enzymes into pancreatic juice under
      physiological and pathological conditions in rabbits.
AB  - To investigate the possible secretion of lysosomal enzymes into pancreatic juice
      during stimulation with a pancreatic secretagogue under both physiological and
      pathological conditions, we measured the amount of cathepsin B, a lysosomal
      enzyme, in the pancreatic juice during the infusion of 6 different concentrations
      of caerulein (0.02, 0.05, 0.2, 0.5, 1.0, and 2.0 micrograms/kg. hr). In one group
      of rabbits the pancreatic duct was only cannulated (free-flow group); in others
      the pancreatic duct was obstructed for 7 hours and secretin was infused at 0.2
      CU/kg. hr (obstructed group). In addition, we evaluated the effect of the
      intraduodenal instillation of a liquid meal (2 g/kg) on the secretion of
      lysosomal enzymes into pancreatic juice. Caerulein stimulated the secretion of
      cathepsin B into pancreatic juice in a dose-dependent manner, as it did that of
      amylase, and at higher concentrations of caerulein (1.0 and 2.0 micrograms/kg.
      hr), both cathepsin B output and amylase output were decreased. There was a
      significant positive correlation between cathepsin B output and amylase output
      into pancreatic juice during stimulation with caerulein. Blockage of the
      pancreatic duct for 7 hours caused a significant rise in serum amylase levels and
      a redistribution of cathepsin B activity in the pancreatic subcellular fractions,
      as a result of which an increased amount of cathepsin B was recovered in the
      pellet obtained by 1000 x g centrifugation for 15 min, which contained many
      zymogen granules. These changes noted after short-term pancreatic duct
      obstruction are very similar to those previously noted in the early stage of diet
      and caerulein-induced experimental pancreatitis, suggesting the colocalization of
      lysosomal enzyme and digestive enzymes. In the duct-obstructed animals, the
      secretion of cathepsin B stimulated by caerulein was significantly greater than
      in the free-flow group. Furthermore, the intraduodenal instillation of a liquid
      meal caused the secretion of cathepsin B into the pancreatic juice along with
      amylase. These results indicate that under physiological conditions, such as food
      intake, lysosomal enzymes are secreted into the pancreatic juice in response to
      stimulation by gut hormones in the same manner as classical pancreatic digestive
      enzymes. Moreover, zymogen colocalized with lysosomal enzymes in duct-obstructed
      animals is secreted into pancreatic juice in increased amounts together with
      digestive enzymes; this finding suggests that lysosomal enzymes play important
      pathophysiological roles in pancreatic juice and that acinar cells are altered to
      maintain cellular organization by secreting the potentially dangerous lysosomal
      enzymes. This pancreatic duct-obstructed rabbit model should be useful in
      clarifying the early events of acute pancreatitis.

PMID- 1382404
TI  - Effect of 3-hour pancreatic duct obstruction on pancreatic lysosomal and
      digestive enzymes in rabbits.
AB  - We studied the effect of short-term (3 hours) pancreatic duct obstruction (PDO)
      on the exocrine pancreas and on the secretion of lysosomal enzymes into the
      pancreatic juice of rabbits during stimulation by pancreatic secretagogues. The
      following evaluations were made: serum amylase levels, pancreatic water content,
      pancreatic amylase, trypsinogen and cathepsin B content, and output of pancreatic
      enzymes and lysosomal hydrolases when stimulated by secretin and caerulein as
      well as the distribution of cathepsin B in subcellular fraction. PDO for 3 hours
      plus secretin infusion caused a significant rise in serum amylase levels,
      pancreatic water content, and pancreatic amylase and trypsinogen content due to
      congestion of digestive enzymes during PDO. There was also a redistribution of
      cathepsin B from the lysosomal fraction to the zymogen fraction. In normal
      rabbits and in those with only secretin infusion, caerulein stimulated the
      secretion of cathepsin B, into pancreatic juice. Just after PDO, the secretion of
      cathepsin B, amylase and trypsinogen significantly decreased. By 24 hours after
      PDO, the output of cathepsin B stimulated by caerulein and secretin had increased
      significantly. Amylase and trypsinogen output were also significantly increased
      at this stage, in both the secretin and caerulein fractions. These results
      indicate that the secretion of lysosomal enzymes into pancreatic juice is
      stimulated by gut hormones, such as caerulein, in the normal physiological state
      and in pathological states, such as PDO. These results also show augmented
      secretion of both lysosomal enzymes and pancreatic digestive enzymes in the
      recovery stage after PDO and their important roles at this stage.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1382405
TI  - [Relationship between endothelial cells and extracellular matrix: investigation
      using the model of angiogenesis in vitro].
AB  - Using model of angiogenesis in vitro, the relationship between endothelial cells
      and extracellular matrix was studied. Endothelial cells of bovine brain
      microvascular vessels (BBECs), carotid artery (BCECs) and aorta (BAECs) were
      cultured on type I collagen gel and Matrigel. BBECs make tubular structures and
      BCECs and BAECs grow and make confluent monolayer on type I collagen gel. BCECs
      and BAECs make tubular structures when second layer of collagen gel was overlaid.
      BBECs, BCECs and BAECs rapidly make tubular structures on Matrigel. These
      morphological changes were not affected by basic fibroblast growth factor. The
      effect of extracellular matrices on the cell kinetics and morphology of cultured
      bovine carotid artery endothelial cells was studied. Endothelial cells show a
      cobble stone appearance on plastic and type I collagen gel. They proliferate and
      make capillary-like structures on reconstituted gels composed of type I collagen
      and basement membrane substrata. And that endothelial cells forming capillary
      like structures were increased with the increase in the concentration of basement
      membrane substrata. Transmission electromicroscopic examination study revealed
      endothelial cells forming capillary-like structures have junctional complexes on
      type I collagen and its mixture with basement membrane substrata. But endothelial
      cells on basement membrane substrata have no junctional complexes. These results
      suggest that BBECs have more potent angiogenic ability than BCECs and BAECs. And
      that proliferation and morphogenesis of endothelial cells are regulated by
      extracellular matrices.

PMID- 1382406
TI  - [The effect of nicardipine on angiogenesis in vitro].
AB  - We studied the effect of nicardipine, a calcium channel blocker, on the
      morphological change of endothelial cells in vitro. Cultured endothelial cells
      derived from bovine carotid artery make tubular structures between collagen gel
      layers. Tube formation of endothelial cells was suppressed by culture with 10(-9)
      10(-5) M of nicardipine in a dose dependent manner. Migration of endothelial
      cells was also suppressed by the same dose of nicardipine. However, proliferation
      of endothelial cells was not enhanced. These findings suggest that nicardipine
      acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of
      endothelial cells.

PMID- 1382407
TI  - The detection of developmental problems in children.
AB  - General practitioners are ideally placed to assist in the identification of
      children whose development is slower than expected for age. In this article
      various methods of detecting developmental delay are discussed, and an algorithm
      is proposed for application in a busy office.

PMID- 1382408
TI  - Biological markers of alcoholism.
AB  - The roles of two categories of biological markers--those relating to alcohol
      consumption and those relating to the risk of developing alcohol related problems
      -are reviewed. Platelet Mono-amino oxidase levels are low in individuals with a
      strong inheritance of their drinking problem (Cloninger Type II alcoholics).
      Elevated gamma-glutamyl transpeptidase (GGT) levels identify regular heavy
      drinkers with a sensitivity between 40-60%. Mean corpuscular volume (MCV) has a
      high specificity (95%) and is useful in detecting regular heavy drinkers in the
      ambulatory care population if other causes of an elevated MCV can be included.

PMID- 1382410
TI  - Cloning of a functional Burkitt's lymphoma polypeptide-binding protein/78 kDa
      glucose-regulated protein (BiP/GRP78) gene promoter by the polymerase chain
      reaction, and its interaction with inducible cellular factors.
AB  - The promoter of the human gene encoding the stress-responsive protein polypeptide
      binding protein/78 kDa glucose-regulated protein (BiP/GRP78) was isolated from
      Burkitt's lymphoma cells by PCR. This promoter DNA segment (termed BiP670) or one
      of its 5' deletion derivatives was fused to the bacterial chloramphenicol
      acetyltransferase gene and introduced into HeLa cells for transient expression.
      BiP670 retained transcriptional activity at both the basal and Ca2+ ionophore
      A23187-inducible levels. However, there was no significant increase in promoter
      activity following a 5 h induction with 7 microM-A23187, and less than 5-fold
      induction at 15 h. In contrast, the steady-state mRNA level was induced by 18
      fold at 5 h. The in vivo transactivation assays with BiP670 5' deletion
      derivatives indicate that the putative A23187-inducible element is located within
      a 70 bp DNA segment (i.e. spanning -39 to -107 bp upstream of the transcriptional
      initiation site). Using an in vitro gel mobility shift assay, A23187-inducible
      nuclear factors were identified from HeLa cell extracts. DNA-binding competition
      experiments also suggest that the 70 bp DNA segment contains a potential sequence
      motif for the binding of the A23187-inducible nuclear factors.

PMID- 1382409
TI  - Involvement of tyrosine kinase and protein kinase C in platelet-activating-factor
      induced c-fos gene expression in A-431 cells.
AB  - In A-431 cells, platelet-activating factor (PAF) induces the expression of c-fos
      and TIS-1 genes in both the absence and the presence of cycloheximide in a
      structurally specific and receptor-coupled manner. We have now investigated the
      molecular mechanisms of this response, particularly in relation to the role of
      protein kinases. Pretreatment of cells with genistein or methyl-2,5
      dihydroxycinnamate (tyrosine kinase inhibitors) or staurosporine (a protein
      kinase C inhibitor) for 20 min abolished the c-fos expression induced by PAF.
      Interestingly, when genistein was added 90 s after addition of PAF, no inhibition
      was observed. Similarly, staurosporine did not inhibit c-fos expression when
      added 8 min after PAF addition to the cells. These inhibitions were dose
      dependent (IC50 for staurosporine was 180 nM, and for genistein 50 microM).
      Simultaneous addition of PAF and phorbol 12-myristate 13-acetate (PMA) did not
      give a synergistic effect on c-fos expression. Pretreatment of cells with PMA had
      no effect on [3H]PAF binding, but abolished the PAF-induced gene expression. PAF
      stimulated gene expression was desensitized if cells were pretreated with PAF.
      Interestingly, epidermal growth factor was able to stimulate c-fos expression in
      PAF-desensitized cells, and thus indicated involvement of distinct mechanisms for
      the two stimuli. Forskolin, an activator of adenylate cyclase, did not induce c
      fos expression and had no effect on the PAF response. Exposure of cells to PAF
      for as little as 1 min, followed by its removal, was sufficient to activate the
      gene expression and demonstrated the rapidity and the exquisite nature of the
      signalling involved in this process. It is concluded that activation of PAF
      receptor (a proposed G-protein-coupled receptor) causes rapid production of
      signals which induce the expression of c-fos gene and that this is mediated via
      tyrosine kinase and protein kinase C.

PMID- 1382411
TI  - The effect of insulin-like growth factor II on glucose uptake and metabolism in
      rat skeletal muscle in vitro.
AB  - The effect of insulin-like growth factor II (IGF II) on the rates of lactate
      formation, glycogen synthesis and glucose transport in the presence of a range of
      concentrations of insulin were investigated using an isolated preparation of rat
      skeletal muscle. IGF II, at a concentration of 65 ng/ml, caused a small but
      significant increase in the rates of these processes at a basal physiological
      insulin concentration (10 muunits/ml), but was without effect in the presence of
      1, 100, 1000 or 10,000 muunits of insulin/ml. Hence IGF II increased the insulin
      sensitivity of this tissue. This effect was removed if the incubation medium was
      supplemented with an equimolar concentration of IGF binding protein 1 (BP1). It
      is suggested that changes in the concentration of IGF II and/or BP1 may regulate
      glucose uptake and metabolism in skeletal muscle and have physiological
      significance in the control of blood glucose level.

PMID- 1382412
TI  - Sequence requirements for processing of proinsulin in transfected mouse pituitary
      AtT20 cells.
AB  - To investigate the sequence requirements for proteolytic processing of
      prohormones at pairs of basic amino acids, normal and mutant proinsulins were
      expressed in the mouse pituitary corticotrophic cell line AtT20. The extent of
      processing was determined by h.p.l.c. analysis of insulin-like immunoreactivity
      secreted into the media of transfected cells. In this model system, normal
      proinsulin was efficiently processed to insulin. The mutant des-38-62-proinsulin,
      in which all but six amino acids of the C-peptide were deleted, was also
      processed to insulin but less efficiently than the wild-type. The mutant Lys64
      Arg65 to Thr64-Arg65 was partially processed to insulin, while the mutant Arg31
      Arg32 to Arg31-Gly32 was not processed at either site. These results indicate:
      (i) that a six-amino-acid spacer between the two pairs of basic amino acids in
      proinsulin is sufficient to permit processing at both sites; (ii) that the
      endoproteinase responsible for cleavage at the Lys64-Arg65 site will also
      recognize Thr64-Arg65; (iii) that the endoproteinase responsible for cleavage at
      the Arg31-Arg32 site will not recognize Arg31-Gly32; and (iv) that the change
      Arg31-Arg32 to Arg31-Gly32 affects processing at the Lys64-Arg65 site.

PMID- 1382413
TI  - Cloning and properties of a cyanide hydratase gene from the phytopathogenic
      fungus Gloeocercospora sorghi.
AB  - The Cht gene encoding cyanide hydratase (CHT, EC 4.2.1.66), which detoxifies HCN
      and is thought to be important in fungal infection of cyanogenic plants, has been
      cloned from the phytopathogenic fungus Gloeocercospora sorghi. The gene was
      isolated by screening an expression library of G. sorghi using a CHT-specific
      antibody and using one of the positive cDNA clones as a probe in Southern
      hybridization to identify a 3.1 kb PstI genomic fragment. This PstI fragment
      expressed CHT activity when transformed into Aspergillus nidulans, a fungus that
      normally lacks CHT activity. Sequence analysis identified a single open reading
      frame of 1,107 base pairs which encodes a polypeptide of 40,904 daltons. The
      deduced amino acid sequence of CHT shares 36.5% identity to a nitrilase from the
      bacterium Klebsiella pneumoniae subsp. ozaenae.

PMID- 1382414
TI  - Lipopolysaccharide induces prostaglandin H synthase-2 in alveolar macrophages.
AB  - Prostaglandin H synthase is a key enzyme in the formation of prostaglandins and
      thromboxane from arachidonic acid. The recent cloning of a second prostaglandin H
      synthase gene, prostaglandin H synthase-2, which is distinct from the classic
      prostaglandin H synthase-1 gene, may dramatically alter our concept of how cells
      regulate prostanoid formation. We have recently shown that the enhanced
      production of prostanoids by lipopolysaccharide-primed alveolar macrophages
      involves the induction of a novel prostaglandin H synthase (J. Biol. Chem.,
      (1992), 267, 14547-14550). We report here that the novel PGH synthase induced by
      lipopolysaccharide in alveolar macrophages is prostaglandin H synthase-2.

PMID- 1382415
TI  - Common peptide epitopes in glycophorin and the endothelial sialoglycoprotein
      gp60.
AB  - Polyclonal anti-serum made against murine glycophorin gp3 (alpha gp) recognizes
      the endothelial albumin binding glycoprotein, gp60. In this study, we
      investigated the nature (peptide vs. carbohydrate) of the common epitope. First,
      a new technique was developed to remove oligosaccharides from glycoproteins that
      were first immobilized on filters and then subjected to beta-elimination. When
      greater than 90% of the glycans of gp60 were removed, alpha gp still recognized
      gp60 without apparent loss of affinity. Second, we used brefeldin A to accumulate
      unglycosylated glycophorin precursors in order to affinity-purify peptide
      specific alpha gp immuno-globulins; these antibodies recognized gp60. Finally,
      alpha gp recognized from in vitro translations a 48 kDa putative polypeptide
      precursor of gp60. These different approaches indicate that gp60 and gp3 have at
      least one common epitope in their peptide backbones.

PMID- 1382416
TI  - Alterations in the subcellular distribution of p21ras-GTPase activating protein
      in proliferating rat acinar cells.
AB  - Rat parotid acinar cells undergo transient proliferation in response to chronic
      administration of the beta-adrenergic agonist isoproterenol or epidermal growth
      factor (EGF). Treatment with these agents caused an increase in tyrosine
      phosphorylation of p21ras-GTPase activating protein (GAP). This phosphorylation
      event was accompanied by a redistribution of the protein from the plasma membrane
      to internal membrane compartments. Separation of subcellular membranes revealed
      increased GAP associated with a low density population of vesicles concomitant
      with growth stimulation as well as to the nuclear membrane, but not the
      nucleoplasm. Upon cessation of hyperplasia induced by isoproterenol,
      phosphorylated GAP present in the plasma membrane returned to control cell
      levels.

PMID- 1382417
TI  - Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of
      cytokine activated cultured endothelial cells.
AB  - Soluble forms of the adhesion molecules ICAM-1, VCAM-1 and E-selectin have been
      detected in supernatants from cytokine activated cultured endothelial cells. The
      release has been quantified using two site enzyme immunoassays. The molecular
      weights of the released molecules have been determined by immunoprecipitation and
      are consistent with the generation of soluble forms by cleavage at a site close
      to the point of membrane insertion.

PMID- 1382418
TI  - Regulation of the 202 gene expression by interferons in L929 cells.
AB  - Type I and II interferons (IFNs) stimulate the expression of the 202 and 2'-5'
      oligoadenylate synthetase (OASE) genes in L929, NIH 3T3 and LM-TK- fibroblastic
      cell lines. In two other cell lines, B16 melanoma and F9 teratocarcinoma, these
      cytokines induce OASE but not the 202 mRNA. In L929 cells, IFN-alpha induces the
      202 mRNA at concentrations between 10 and 10(3) units/ml. To achieve maximal
      induction of the 202 mRNA, continuous exposure of L929 cells to IFN-alpha is
      necessary, whereas 30 minutes of exposure are sufficient to trigger maximal
      upregulation of the OASE transcript. The induction of the 202 mRNA is the
      consequence of both transcriptional and post-transcriptional events.
      Cycloheximide, a known inhibitor of protein synthesis, does not block the
      induction of 202 mRNA by IFN-alpha, demonstrating that new protein synthesis is
      not required for this effect. Protein kinase C, arachidonic acid metabolism via
      the cyclooxygenase or the lipoxygenase pathways and cAMP are not involved as
      second messengers in the induction of the 202 mRNA by IFN-alpha in L929 cells.

PMID- 1382419
TI  - Cytosolic Ca(2+)-induced modulation of ion selectivity and amiloride sensitivity
      of a cation channel and beta agonist action in fetal lung epithelium.
AB  - The cytosolic Ca2+ concentration ([Ca2+]i) affects many cell functions, including
      the modulation of ion channel activity. In this study patch clamp experiments
      using primary cultures of fetal distal lung epithelium (FDLE) demonstrated that
      the elevation of [Ca2+]i modulated a 25pS amiloride-blockable non selective
      cation (NSC) channel's ion selectivity and sensitivity to amiloride. An elevation
      of [Ca2+]i from 0.1 microM to 1mM both increased open probability (Po) and
      decreased the ratio of the permeability to Na to the permeability to K (PNa/PK)
      from 1.96 +/- 0.11 (SEM, n = 6) to 0.88 +/- 0.04 (n = 6). Within the range of
      [Ca2+]i from 0.1 microM to 100 microM amiloride (0.5 microM) decreased Po,
      however amiloride (0.5 microM) no longer affected Po of the NSC channel when
      [Ca2+]i was increased to 1mM under physiologic membrane potentials. A beta
      adrenergic agonist (terbutaline, 10 microM) increased Po in cell-attached patches
      from almost 0 (Po less than 0.01; n = 9) to 0.39 +/- 0.09 (n = 9) and [Ca2+]i
      from 40 +/- 6nM (n = 9) to more than 1 microM. This suggested that amiloride
      blockable NSC channel activity and ion permeability are modulated by changes in
      [Ca2+]i near physiologic membrane potentials and a beta adrenergic agonist
      increases [Ca2+]i to more than 1 microM (unlike other epithelial including adult
      alveolar cells) which is associated with activation the NSC channel.

PMID- 1382420
TI  - Immunological and conformation characterization of a phosphorylated
      immunodominant epitope on the paired helical filaments found in Alzheimer's
      disease.
AB  - The immunological recognition pattern of one of the most commonly used monoclonal
      antibodies, PHF-1, which detects the paired helical filaments of Alzheimer's
      disease, exhibits a high degree of similarity with the recognition of a
      polyclonal antibody, anti-T3P, raised against a synthetic phosphopeptide,
      GAEIVYKS(Phospho)PVVSGD, corresponding to amino acids 389-402 of the microtubule
      associated protein tau. A panel of 16 synthetic non-phosphorylated and
      phosphorylated peptides, excised from different regions of tau and peptide
      analogs thereof, were used to show that PHF-1 is indeed directed against the T3
      fragment. Circular dichroism spectroscopy shows that the phosphorylated peptide
      exhibits a limited propensity to form intramolecular beta-pleated sheets, and
      alteration is found in the reverse-turn structure that dominates the middle
      section of the molecule. The shift in the turn-forming amino acids may also allow
      a stacking procedure, may interfere with microtubule assembly, and, consequently,
      may be accountable for deposit formation.

PMID- 1382421
TI  - The non specificity of specific nitric oxide synthase inhibitors.
AB  - L-NAME (Nw-Nitro-L-arginine methylester) and L-NMMA (NG- Monomethyl-L-arginine,
      monoacetate) are used widely as nitric oxide (NO) synthase inhibitors. Because of
      their functional groups (alcohols, amines and carboxylates), it appeared that
      they could interact with iron in a variety of systems. Using three in vitro
      models we observed these two compounds had inhibitory effects on cytochrome C
      reduction by ferrous iron, by ferrous iron accelerated by an unsaturated fatty
      acid or by epinephrine. This suggests that L-NAME and L-NMMA could have effects
      in iron containing systems found intracellularly apart from their inhibition of
      (NO) synthesis.

PMID- 1382422
TI  - Effects of insulin and tyrosine kinase inhibitor on ion transport in the alveolar
      cell of the fetal lung.
AB  - We studied the effect of insulin and lavendustin-A (a tyrosine kinase inhibitor)
      on the short-circuit current (ISC) of primary cultures of fetal distal rat lung
      epithelium (FDLE). Insulin (2 microM) on the basolateral side of the monolayer
      increased ISC from 5.76 +/- 0.83 microA/cm2 (SEM, n = 7) to 7.23 +/- 1.00
      microA/cm2 (p less than 0.01) under control conditions, and from 1.00 +/- 0.31
      microA/cm1 to 1.53 +/- 0.34 microA/cm2 (p less than 0.05, n = 4) when amiloride
      (10 microM) was present on the apical side of the monolayer. Thus insulin
      increased both the amiloride-sensitive and insensitive ISC with the insulin
      induced increase in ISC in the absence of amiloride (1.47 +/- 0.22 microA/cm2, n
      = 7) being significantly larger than that in the presence of 10 microM amiloride
      (0.53 +/- 0.14 microA/cm2, n = 4; p less than 0.025). Insulin's effect reached
      steady state in 1 hr. Lavendustin-A (10 microM), a tyrosine kinase inhibitor,
      applied to the apical side of the monolayer attenuated but did not completely
      block insulin's ability to increase in ISC; i.e., insulin increased ISC in
      lavendustin-A treated monolayers (0.63 +/- 0.09 microA/cm2, n = 5; p less than
      0.0025) but the increase was significantly smaller than that without the
      pretreatment of lavendustin-A (p less than 0.05). In the presence of amiloride
      (10 microM) and lavendustin-A (10 microM) insulin was no longer able to increase
      ISC (change in ISC = 0.04 +/- 0.03 microA/cm2, n = 6), suggesting that
      lavendustin-A had blocked the insulin's effect on the amiloride-insensitive ISC.
      Lavendustin-A (10 microM) had no significant effect on the basal ISC in control
      and amiloride treated monolayers. Our studies demonstrate that insulin increases
      amiloride-insensitive ISC in FDLE via lavendustin-A sensitive tyrosine kinase and
      that insulin's action on the amiloride-sensitive ISC of FDLE is mediated through
      a lavendustin-A insensitive (and presumably tyrosine kinase-independent) pathway.

PMID- 1382424
TI  - A comparison of drug binding sites on mammalian albumins.
AB  - The fluorescent probes warfarin and dansylsarcosine are known to selectively
      interact with binding sites I and II, respectively, on human albumin. This paper
      investigates whether similar binding sites exist on bovine, dog, horse, sheep and
      rat albumins. Binding sites on albumins were studied by: (1) displacement of
      warfarin and dansylsarcosine by site I (phenylbutazone) and site II (diazepam)
      selective ligands; (2) the effects of non-esterified fatty acids (carbon chain
      lengths: C5-C20) and changes in pH (6-9) on the fluorescence of warfarin and
      dansylsarcosine; and (3) the ability of site selective ligands to inhibit
      hydrolysis of 4-nitrophenyl acetate. For bovine, dog, horse, human and sheep
      albumins the fluorescence of bound warfarin and dansylsarcosine was selectively
      decreased by phenylbutazone and diazepam, respectively. For these albumins medium
      chain fatty acids (C1-C12) reduced the fluorescence of dansylsarcosine (maximum
      inhibition with C9) whereas long chain acids (C12-C20) enhanced the fluorescence
      of warfarin (maximum increases with C12). In addition, changes in pH from 6 to 9
      increased the fluorescence of warfarin and although site I ligands
      (warfarin/phenylbutazone) had no pronounced effects on 4-nitrophenyl acetate
      hydrolysis, site II ligands (dansylsarcosine/diazepam) significantly inhibited
      this reaction. Rat albumin behaved differently from the other albumins studied in
      that the C12-C20 fatty acids and changes in pH did not enhance the fluorescence
      of warfarin. Moreover, the differential effects of site I and site II ligands on
      the fluorescence of warfarin/dansylsarcosine and hydrolysis of 4-nitrophenyl
      acetate were less apparent with rat albumin. The results suggest bovine, dog,
      horse and sheep albumins have binding sites for warfarin and dansylsarcosine with
      similar properties to sites I and II on human albumin. By contrast, the warfarin
      binding site and to a lesser degree the dansylsarcosine site, of rat albumin have
      different characteristics from these sites on the other albumins studied.

PMID- 1382423
TI  - Tyrosine-protein kinase inhibition in human erythrocytes by polyphosphoinositides
      (PIP and PIP2).
AB  - In human erythrocytes Ser/Thr- and Tyr-phosphorylations of cytoplasmic domain of
      band 3 are catalyzed by casein kinase I and Tyr-protein kinase respectively, both
      distributed between cytosol and membrane structures. The results reported here
      show that purified cytosolic Tyr-protein kinase activity, assayed on added
      substrates such as poly(Glu,Tyr)4:1 and isolated chymotryptic fragments of band 3
      cytoplasmic domain (cdb3), is potently inhibited by PIP and even more by PIP2.
      Similar inhibitory effects are displayed by these polyphosphoinositides also on
      the endogenous Tyr-phosphorylation of band 3, when they are added to the isolated
      native membranes, thus suggesting their involvement in regulating in-vivo Tyr
      phosphorylation of membrane proteins.

PMID- 1382425
TI  - Inhibition of platelet activation by tyrosine kinase inhibitors.
AB  - Protein tyrosine kinase (PTK) blockers (tyrphostins) inhibit in a dose-dependent
      fashion thrombin-induced aggregation and serotonin release with IC50 values in
      the 10-35 microM concentration range. The inhibition of thrombin-induced
      aggregation correlates with their potency in inhibiting phosphorylation of
      proteins on tyrosine residues. Using metabolically 32P-labelled human platelets,
      it was found that the tyrphostins have no effect on the decrease in
      [32P]phosphatidylinositol bisphosphate but prevent the replenishment of
      [32P]polyphosphoinositide. Tyrphostins decreased [32P]phosphatidic acid
      production induced by thrombin, although never by more than 50%, and only delayed
      the peak of diacylglycerol, suggesting that phospholipase C was still activated.
      Tyrphostins inhibited the thrombin-elicited early phosphorylation of p43 and p20,
      substrates for protein kinase C (PKC) and myosin light chain kinase,
      respectively, at short times of activation. This inhibition, however, was
      overcome after 1 min of stimulation with thrombin. Tyrphostin AG213 also
      inhibited platelet aggregation and tyrosine protein phosphorylation induced by
      phorbol myristate acetate (PMA), but did not inhibit pleckstrin phosphorylation.
      These results suggest that thrombin induces the phosphorylation of proteins on
      tyrosine residues which most probably results in the activation of
      phosphoinositide kinases. The ability of tyrphostins to inhibit phosphorylation
      of p43 and p20 when induced by thrombin but not when induced by PMA confirms that
      PTKs may be involved subsequent to PKC activation.

PMID- 1382426
TI  - Inhibition of mouse glutathione transferases and glutathione peroxidase II by
      dicumarol and other ligands.
AB  - Dicumarol, often used as a specific inhibitor of DT diaphorase (NAD(P)H:(quinone
      acceptor) oxidoreductase; EC 1.6.99.2), was found to potently inhibit GSH
      transferases (EC 2.5.1.18). Dicumarol exhibited an IC50 of 11 microM in
      inhibiting the conjugation of 1-chloro-2,4-dinitrobenzene (50 microM) by GSH
      transferase GT-8.7, the major hepatic class mu isoenzyme of CD-1 mice. The
      activities of GT-8.7 and of the class pi isoenzyme, GT-9.0, toward a carcinogenic
      substrate, 4-nitroquinoline 1-oxide (100 microM), were inhibited by dicumarol
      with IC50 values of 14 and 9 microM, respectively. Dicumarol also affected GSH
      peroxidase II activity, inhibiting the reduction of cumene hydroperoxide by GT
      10.6, the predominant class alpha GSH transferase of mouse liver, with an IC50 of
      14 microM. GSH peroxidase I (EC 1.11.1.9) and GSH peroxidase II activities were
      resolved by chromatography of liver and testis cytosols. While inhibiting GSH
      peroxidase II with IC50 of 9-10 microM, dicumarol did not affect the activity of
      the selenoenzyme, GSH peroxidase I. Whereas several other non-substrate ligands
      were more potent inhibitors of 1-chloro-2,4-dinitrobenzene conjugation, dicumarol
      effectively inhibited GSH transferase and GSH peroxidase II activities in the
      range of dicumarol concentrations frequently used for detection of DT diaphorase
      action. These results indicate that physiological consequences resulting from the
      use of supramicromolar concentrations of dicumarol should not be interpreted in
      terms of DT diaphorase inhibition alone.

PMID- 1382427
TI  - [Bone marrow involvement in Whipple's disease].
AB  - The authors present the case of a 57 years old woman who had atypical Whipple's
      disease characterized solely by migratory arthralgia, weight loss and unexplained
      anemia which had lasted for 5 years. Once the diagnosis of Whipple's disease was
      established on abdominal lymph node biopsy, the retrospective study of a bone
      marrow biopsy revealed the presence of PAS-positive sickle-formed particles
      within medullary macrophages. Review of the literature attests the rarity of ante
      mortem diagnosis of Whipple's disease in bone marrow preparations. We suggest
      that bone marrow biopsies stained with the PAS technique be employed in clinical
      settings of chronic migratory arthralgia and unexplained anemia.

PMID- 1382428
TI  - Comparison of computer-based learning and seminar teaching of pulmonary
      auscultation to first-year medical students.

PMID- 1382429
TI  - Quinolinehydrazones as inhibitors of retroviral reverse transcriptase.
AB  - The inhibitory activity of a series of 2- and 4-quinolinehydrazones on retroviral
      reverse transcriptase has been studied on enzymes from M-MuLV, RAV-2, and on a
      crude lysate of HIV-1, assuming the first two enzymes as potential models of the
      third. The highest activity is mainly found in lipophilic, water soluble 4
      quinolinehydrazones. The inhibitory activity of these compounds decreases in
      changing from the M-MuLV to the RAV-2, and HIV-1 enzymes, in this order.

PMID- 1382430
TI  - [Growth behavior of Enterobacteriaceae in BRILA-MUG-broth and in different
      modifications of broth].
AB  - Both substances, brilliant green and bile, inhibit the growth of gram-positive
      bacteria in culture media and selectively enrich gram-negative bacteria.
      Therefore, the brilliant green-lactose-bile broth (BRILA) and the BRLA broth
      supplemented with tryptophan and methyl-umbelliferyl-beta-D-glucuronide (BRILA
      MUG) contain brilliant green as well as bile. Because BRILA-MUG broth as a
      selective enrichment and differentiating medium of faecal coliform and total
      coliform bacteria, E. coli and coliforms, respectively, is recommended for
      testing samples of surface water according to the EC guidelines for bathing
      waters (no. 76/160 EWG), the question arose of the optimal combination of
      components in the BRILA-MUG broth. As the described investigations show, the
      addition of buffer substances did not improve the culture properties of the BRILA
      MUG broth. However, the original BRILA broth was improved by supplementing it
      with buffer substances such as CaCO3 or Na2HPO4. The same effect of culture
      improvement was obtained by removing brilliant green. This modification of BRILA
      broth is practically identic with the well-known MacConkey broth. On the other
      hand, the modification of omitting bile from the original BRILA broth causes a
      remarkable impairment of the culture properties lowering bacterial counts per ml
      by 3-5 log. The observations suggest that brilliant green inhibits both, gram
      positive bacteria as well as the gram-negative Enterobacteriaceae. Therefore, it
      is a selective substance of doubtful usefulness.

PMID- 1382431
TI  - Identification of antigenic regions of the human Ro 60 kDa protein using
      recombinant antigen and synthetic peptides.
AB  - Autoantibodies reacting with the human Ro 60 kDa protein are present in anti
      Ro/SS-A positive sera from patients with several different connective tissue
      diseases including Sjogren's syndrome and systemic lupus erythematosus. To
      investigate the humoral immune response to this protein, the pattern of antibody
      recognition of recombinant Ro 60 kDa proteins encoded by both full-length and
      deletion clones was analysed by immunoblotting. An antigenic region recognized by
      nearly all anti-Ro 60 kDa positive sera was found to reside in the middle part of
      the protein. In addition, some sera reacted with two other antigenic regions
      located in the amino-terminal and carboxyl-terminal part of the protein. For
      further mapping, overlapping peptides covering the most frequently recognized
      region of the protein were synthesized by solid-phase methods and used as
      antigens in ELISA. Three major patterns of reactivity to Ro 60 kDa peptides were
      found. These results not only indicate the presence of an immunodominant region
      but also heterogeneity in the autoimmune human response to the Ro 60 kDa antigen.

PMID- 1382432
TI  - Neurochemical effects of electrically and chemically induced seizures: an in vivo
      microdialysis study in the rat hippocampus.
AB  - This study examined the effects of electroconvulsive shock (ECS) on interstitial
      concentrations of serotonin (5-HT), its metabolite 5-hydroxyindoleacetic acid (5
      HIAA), acetylcholine and choline, and the dopamine metabolite homovanillic acid
      (HVA) in the hippocampus of freely moving rats using online brain microdialysis.
      The effects of ECS on 5-HT, 5-HIAA, and HVA were compared to the effects of
      seizures induced by the convulsant agent flurothyl. Interstitial concentrations
      of 5-HT increased several fold in response to ECS and this increase was
      accompanied by a significant increase in the concentration of HVA. Acetylcholine
      and choline concentrations were also increased significantly by ECS. The ECS
      induced increase in interstitial 5-HT was markedly reduced when the voltage
      dependent sodium channel blocker tetrodotoxin (1 mumol/L) was added in the
      perfusion solution, indicating that the observed increase was of neuronal origin.
      Interstitial concentrations of 5-HT also increased in response to flurothyl
      induced seizures and this increase was accompanied by a significant increase in
      the concentration of HVA. These results provide direct in vivo evidence that
      interstitial concentrations of 5-HT increase several fold in response to both ECS
      and flurothyl-induced seizures. These observations are discussed in relation to
      the hypothesized role of 5-HT in ECS-induced memory deficits.

PMID- 1382433
TI  - Arthritis-regulating determinants on the collagen-like complement component C1q.

PMID- 1382434
TI  - Sequence homology between spirochaete flagellin and human myelin basic protein.

PMID- 1382435
TI  - Antigenic mapping of a human lambda light chain: correlation with three
      dimensional structure.
AB  - Although the amino acid sequence and three-dimensional structure of human
      immunoglobulin light chains have been known for more than 15 years, the location
      of antigenic markers characteristic of lambda chains has not been determined.
      Here, we use a set of synthetic overlapping peptides to completely model the
      sequence of the lambda chain Mcg and test these for the binding of rabbit and
      goat antisera specific for lambda chain determinants. We assess peptide
      contributions to lambda-antigenic reactivity and also to identify a portion of C
      region where conformational factors contribute to the antigenicity. Specific
      determinants occur both in the constant and variable (first and third framework)
      domains of the molecule. The fourth framework of the variable region, a segment
      specified by the joining gene, is also recognized and cross-reacts antigenically
      with the homologous region of T cell receptor beta chains. Major lambda specific
      determinants are localized in the N- and C-terminal segments, which are linear
      and devoid of major conformational folding. Other segments that are strongly
      antigenic, such as the third framework of the V region (residue 78-93) and a
      segment of the constant region (residues 177-192), show strong conformational
      dependence in antigenicity.

PMID- 1382436
TI  - Induced resistance of trypsin to sodium dodecylsulfate upon complex formation
      with trypsin inhibitor.
AB  - The stabilities of trypsin and soybean trypsin inhibitor in sodium dodecylsulfate
      (SDS) were examined by SDS-polyacrylamide gel electrophoresis (PAGE). Both
      samples contained several bands, all of which migrated to positions corresponding
      to the appropriate molecular weight or less, even when the samples were unheated,
      suggesting that both the trypsin and trypsin inhibitor are susceptible to SDS
      induced denaturation. When they were mixed together prior to addition of SDS-PAGE
      sample buffer (1% SDS), a new smearing band appeared which corresponded to a
      molecular weight of around 46,000, suggesting that these proteins form a stable
      complex in SDS. This was confirmed by electroblotting and sequence analysis,
      which indicated that this band contains both the trypsin and inhibitor sequences.
      At a fixed concentration of the inhibitor, increasing concentrations of the
      trypsin resulted in an increase in the intensity of the complex band. When the
      mixture was heated for 10 min in 1% SDS, the complex band disappeared in a
      temperature-dependent manner. The melting temperature determined under the
      experimental conditions used was about 35 degrees C. Similar results were
      obtained with Bowman-Birk trypsin inhibitor, except that the complex with the
      above inhibitor had a higher melting temperature, around 41 degrees C, suggesting
      that the Bowman-Birk inhibitor/trypsin complex is more stable than the soybean
      inhibitor/trypsin complex.

PMID- 1382437
TI  - Immunological evidence for a conformational difference between recombinant bovine
      rhodanese and rhodanese purified from bovine liver.
AB  - Rhodanese has been utilized as a model enzyme for the study of protein structure
      function relationships. The enzyme has recently been cloned and the recombinant
      enzyme is now available for investigation. However, prior to use in structure
      function studies, the recombinant enzyme must be shown to have the same structure
      and activity as the bovine liver enzyme used in the previous studies. An
      immunological study of the conformations of these enzyme conformers is described.
      Three antibodies (two monoclonal and one polyclonal, site-directed antibody) were
      shown to detect distinct and nonoverlapping epitopes. The epitopes of the
      monoclonal antirhodanese antibodies (R207 and MAB11) were mapped to the same CNBr
      digest fragment of the amino terminal domain of rhodanese, and the epitope of the
      site-directed antibody prepared against the interdomain tether sequence of
      rhodanese (PAT-T1) was mapped to that region of rhodanese (residues 142-156). The
      rhodanese conformers were studied by monitoring the accessibility of the epitopes
      recognized by each antibody in each conformer using an indirect ELISA. None of
      the antibodies could detect its epitope on the purified liver enzyme. Two of the
      antibodies (R207 and PAT-T1) could also not detect their epitopes on the
      recombinant enzyme. However, MAB11 did detect a conformational difference between
      the natural and recombinant rhodanese conformers, indicating the conformational
      difference is localized in the first 73 amino acids of rhodanese. This difference
      presumably reflects the difference in the histories of the two enzymes and may be
      due to differences in enzyme folding, differences in the purification procedures,
      and differences in storage conditions--all of which could influence the final
      conformation of the enzyme.

PMID- 1382438
TI  - High-level expression of recombinant human FK-binding protein from a fusion
      precursor.
AB  - The human peptidyl-prolyl isomerase FK-binding protein (FKBP) was cloned as a
      fusion partner with CMP-KDO synthetase (CKS), and the resultant construct was
      characterized as an improved high-expression source for FKBP. The CKS-FKBP fusion
      was expressed as a soluble protein at levels approaching 1 gm/L in Escherichia
      coli fermentations. The fusion protein was purified to near homogeneity by a one
      step ammonium sulfate fractionation of whole cell lysate. After selective
      cleavage, the fusion precursor produced yields approaching 300 mg of purified
      FKBP per liter of harvested culture, a approximately 30 to 60-fold increase over
      that observed for a nonfusion construct. Selective cleavage of the fusion
      partners was accomplished using either hydroxylamine or specific, limited
      proteolysis. Once separated from the CKS fusion partner, the FKBP was isolated in
      a single step by either reversed-phase HPLC or chromatography on Q-Sepharose. For
      comparison of physical and chemical properties, a nonfusion construct of
      recombinant human FKBP was expressed in E. coli and isolated. The purified FKBPs
      exhibited expected SDS-PAGE molecular weights and N-terminal sequences. The
      proteins had similar proton NMR spectra and binding to [3H]FK-506. The fusion
      construct, CKS-FKBP, was also found to bind [3H]FK-506. These data indicate that
      FKBP fused to the C-terminus of CKS folds independently of the fusion partner and
      suggests the fused FKBP adopts a conformation resembling that of the native
      protein.

PMID- 1382439
TI  - Both ends of Escherichia coli ribosomal protein S13 are immunochemically
      accessible in situ.
AB  - To investigate the structure of Escherichia coli ribosomal protein S13 in 30S
      ribosomal subunits, we have previously generated 22 S13 specific monoclonal
      antibodies and mapped their specific epitopes to the S13 sequence. The
      availability of these S13 epitopes in situ has been further examined by
      incubating these monoclonal antibodies with 30S ribosomal subunits and analyzing
      formation of monoclonal antibody-linked ribosome dimers by sucrose gradients
      centrifugation. We have found that none of the 22 monoclonal antibodies makes
      ribosome dimers individually as do typical antisera. However, one monoclonal
      antibody, designated AS13-MAb 2, reacts with 30S ribosomal subunits to form
      immunocomplexes sedimenting faster than subunit monomers. When AS13-MAb 2 is
      paired with any one of three monoclonal antibodies directed to the S13 C-terminal
      epitopes, dimer formation is observed. Other pairs of monoclonal antibodies
      directed to distinct S13 epitopes have been tested similarly for dimer formation.
      Monoclonal antibody AS13-MAb 22, directed to the N-terminal region of 22
      residues, also causes subunits to form typical dimers, but only if paired with
      one of the three monoclonal antibodies directed to the S13 C-terminal region. The
      close proximity of the epitopes recognized by AS13-MAbs 2 and 22 has been
      established by the mutual competition between the antibodies binding to intact
      30S subunits. These results corroborate our previous observation, using
      polyclonal antibodies, that S13 has more than one epitope exposed on 30S
      subunits. Our finding that sequences on both ends of the S13 molecule are
      immunochemically accessible provides information about the molecular organization
      of S13 in situ.

PMID- 1382440
TI  - Mast cell degranulating (MCD) peptide analogs with reduced ring structure.
AB  - Mast cell degranulating (MCD) peptide, a component of bee venom, is a 22 amino
      acid peptide with two disulfide bridges. In this first structure-activity study
      of MCD peptide, three analogs were synthesized and tested: two analogs shortened
      by omitting sequences 6-10 and 8-13, respectively, and one analog lacking the
      disulfide bridge between cysteine residues 5 and 19. These analogs were
      synthesized by solid-phase methods and were compared to MCD peptide in two assays
      for inflammation: histamine release from mast cells and superoxide anion release
      from neutrophils. All three analogs produced histamine release, although with
      only about one fifth of the activity of MCD peptide. Superoxide anion-releasing
      activity, however, did not parallel histamine release. MCD peptide did not
      release superoxide anion, while the 6-10 and 8-13 deletion analogs were strong
      and weak stimulants, respectively, of this anion. CD spectra showed that the
      secondary structures of the three analogs were very similar to that of MCD
      peptide, so that a change in secondary structure cannot completely explain the
      changes in releasing activities. Charge differences between the two deletion
      analogs and MCD peptide may explain some of the differences in activity. This is
      the first demonstration that the various activities of MCD peptide can be
      separated, and provides a lead through which the purported antiinflammatory
      activity of MCD peptide may possibly be explored in the future.

PMID- 1382441
TI  - Aberrant expression of the simple epithelial type II keratin 8 by mouse skin
      carcinomas but not papillomas.
AB  - Keratins have been demonstrated to be suitable markers of changes taking place
      during epithelial neoplasia. Therefore, we analyzed 18 mouse skin tumors (nine
      papillomas and nine squamous cell carcinomas), induced either by two-stage
      carcinogenesis with 7,12-dimethylbenz[a]anthracene(DMBA)/12-O
      tetradecanoylphorbol-13-acetat e or complete carcinogenesis with DMBA, by
      immunofluorescence with a monoclonal antibody to keratin (K) 8 (TROMA-1).
      Immunoperoxidase staining and immunoblotting were also used on selected tumor
      samples to further explore for the presence of K8. All of the papillomas tested
      were negative for the presence of K8, whereas the carcinomas were positive. The
      level of K8 expression in carcinomas showed a positive correlation with the
      degree of malignancy. Northern blot analysis using a K8 cDNA probe suggested that
      control of K8 expression in mouse skin tumors occurs at the transcriptional
      level. Double-label immunofluorescence staining using TROMA-1 and RK13 antibodies
      demonstrated that K8 did not generally colocalize with K13, a keratin normally
      found in internal stratified epithelial but aberrantly expressed in mouse
      epidermal tumors. Furthermore, tumors expressing high levels of K8 showed a
      reduced expression of K13. Histological examination of immunoperoxidase-stained
      tumors demonstrated that K8-positive cells were mainly found in anaplastic areas,
      whereas K13 foci were restricted to well-differentiated regions. Our results
      demonstrate that K8 expression is a marker of late stages of carcinoma
      progression in the mouse skin carcinogenesis model.

PMID- 1382442
TI  - Expression of the transin, c-fos, and c-jun genes in rat transplantable
      osteosarcomas and malignant fibrous histiocytomas.
AB  - The expression of the transin, c-fos, and c-jun genes was assessed in
      transplantable osteosarcomas and malignant fibrous histiocytomas, as well as in
      pancreatic duct adenocarcinomas and hepatocellular carcinomas of rats and
      hamsters. Northern blot analysis revealed that both an undifferentiated
      osteosarcoma of spontaneous origin (SOS) and 4-hydroxyaminoquinoline 1-oxide (4
      HAQO)-induced malignant fibrous histiocytomas with metastatic potential to the
      lung showed remarkably increased expression of transin mRNA transcripts. This was
      not the case for the other tumors. Interestingly, levels of transin mRNA were
      lower in lung metastatic lesions than in primary subcutaneous SOS tumors. The
      primary SOS and MFH expressed both c-fos and c-jun genes in conjunction with the
      transin gene, whereas the non-transin expressers, a 4-HAQO-induced osteosarcoma
      (COS) and the pancreatic duct adenocarcinomas, demonstrated one or the other, but
      not both. These results suggest a possible involvement of transin expression in
      the progression of spontaneous osteosarcomas and 4-HAQO-induced malignant fibrous
      histiocytomas in rats. Expression of the c-fos and c-jun genes may play a
      regulatory role in this process.

PMID- 1382443
TI  - p53 mutations are absent from carcinogen-induced mouse liver tumors but occur in
      cell lines established from these tumors.
AB  - Mutations in the p53 gene are frequent genetic alterations in human
      hepatocellular carcinomas. We have examined, by single-strand conformation
      polymorphism analysis of polymerase chain reaction products, a total of 93
      carcinogen-induced liver tumors from mice of three different strains (C3H/He,
      C57BL/6J, and B6C3F1) for the presence of p53 aberrations. Hepatoma lines,
      established from 12 liver tumors, were also included in the analysis. While
      structural aberrations of the p53 gene were not detected in any of the primary
      mouse liver tumors analyzed, single-base substitutions occurred at different
      locations within the p53 gene in three of the cell lines during in vitro
      propagation. One hepatoma line carried two point mutations on separate alleles.
      All four mutations were either G:C----C:G or C:G----G:C transversions. Mutations
      at codon 61 of the c-Ha-ras gene, which were frequent in primary liver tumors
      from C3H/He and B6C3F1 mice, were not detected in the hepatoma lines. Our data
      indicate (i) that c-Ha-ras but not p53 mutations play an important role during
      the early stages of mouse hepatocarcinogenesis and (ii) that p53 mutations confer
      a selective growth advantage to the mutated hepatoma cells in vitro.

PMID- 1382444
TI  - T-cell recognition of oncogene products: a new strategy for immunotherapy.

PMID- 1382445
TI  - T-cell receptors: germline polymorphism and patterns of usage in demyelinating
      diseases.
AB  - The genomic organization of the T-cell receptor (TCR) gene complexes accounts for
      many central aspects of T-cell immunobiology, including specificity and
      diversity. Recent data indicate that polymorphism of TCR genes is present within
      a species and may influence the immune phenotype of an individual. Such
      polymorphism has been detected by RFLP, by the presence of large regions of
      insertion or deletion of germline DNA, and by allelic variability of individual
      gene segments that are expressed. In addition to allelic variation of TCR genes,
      immune responses may also be influenced by the repertoire of the TCR molecules
      that are expressed by responding T-cell populations. In some situations,
      pathogenic T-cell responses may involve expression of limited numbers of TCR gene
      families. This is true, for example, in experimental allergic encephalomyelitis,
      an autoimmune nervous system disease mediated by T-cells reactive to myelin basic
      protein. In the human disease counterpart, multiple sclerosis, a more complex
      pattern of T-cell recognition to the putative autoantigen is generally present,
      although in some individuals a restricted response may occur. Specific therapies
      targeted to certain TCR molecules represents a promising approach to chronic
      inflammatory diseases in humans. The efficacy of such therapies will be
      determined in part by the TCR repertoire expressed in individual disease
      situations and by the potential for plasticity in the pathogenic T-cell response
      that may exist.

PMID- 1382446
TI  - Long-term consequences of interleukin-6 overexpression in transgenic mice.
AB  - With the aim of using interleukin-6 (IL-6)-inducible promoters to express
      transgenes, we investigated the long-term consequences of high levels of IL-6 in
      mice. As a first step, we generated transgenic mice constitutively expressing the
      murine IL-6 at a level sufficient to induce IL-6-responsive genes. These mice
      were analyzed with respect to the indirect and direct consequences of elevated IL
      6 expression over a time period of about 2 years. Although biologically active IL
      6 was expressed from the transgene and different alterations could be documented
      (less immature B cells in bone marrow, expression of IL-6-inducible liver genes),
      the mice appeared healthy and could easily be used for breeding. Only in mice
      older than 18 months did we find a high incidence of lymphomas associated with
      different tissues. These results indicate that the side effects of long-term
      treatment with IL-6 are relatively moderate, and that IL-6 might be used to
      mediate the expression of heterologous genes in the context of functional
      studies.

PMID- 1382448
TI  - Model systems in iontophoresis--transport efficacy.

PMID- 1382447
TI  - Human interferon regulatory factor 1: intron-exon organization.
AB  - Interferon (IFN) regulatory factor 1 (IRF-1) is a transcriptional regulatory
      protein that mediates the transcriptional activation of the IFN-alpha and IFN
      beta genes by viruses and IFNs. To characterize the mechanisms that govern the
      level of IRF-1 in cells, we isolated the IRF-1 gene and characterized the
      structure of its intronic and exonic domains and of its regulatory promoter
      region. A human placental genomic library was screened with an IRF-1 cDNA probe,
      and two clones that contained the IRF-1 gene and its 5' regulatory region were
      obtained. We used these clones to determine the complete nucleotide sequence for
      the IRF-1 gene, finding that the IRF-1 gene spanned 7.72 kb of DNA and included
      10 exons and 9 introns. When the deduced amino acid sequences were compared among
      different species, the most conserved exons were exons 2, 3, and 4, in which the
      putative DNA binding domain for the IRF-1 protein is located.

PMID- 1382449
TI  - Concurrent measurement of serotonin metabolism and single neuron activity changes
      in the lateral hypothalamus of freely behaving rat.
AB  - To further investigate the activity of serotonin neurons in relation to feeding
      behavior, the metabolic activity of the serotonergic system and single neuron
      activity changes in the lateral hypothalamic area (LHA) were investigated
      concurrently in freely behaving rats. The extracellular concentration of 5
      hydroxyindoleacetic acid (5-HIAA), a metabolic product of serotonin in the LHA,
      began to increase concomitantly with the early stage of nocturnal eating. The
      increased 5-HIAA returned to the basal level within 3 or 4 h. In conjunction with
      the increase in serotonin metabolism, activity of 12 out of 30 LHA neurons (40%)
      increased, whereas it decreased in 7 (23%), and in 11 (37%) it showed no change.
      An intracerebroventricular injection of lisuride suppressed the increased
      activity in 7 of the 12 neurons, but had no effect on the others. These results
      suggest that the concurrent increase in serotonin metabolism and neuron activity
      changes in the LHA may occur in the early portion of the nocturnal eating period,
      and may be important in controlling feeding behavior.

PMID- 1382450
TI  - Axonal transport, imaging, and the diagnosis of nerve compression.

PMID- 1382451
TI  - Self-reported prevalence of disability after subarachnoid haemorrhage, with
      special emphasis on return to leisure and work.
AB  - The prevalences of motor and language impairments and of disabilities in
      activities of daily living (ADL), leisure and work were investigated in a
      consecutive series (n = 296) of long-term survivors of subarachnoid haemorrhage
      (SAH). Motor and language impairments were present in 17 and 20%, respectively.
      The majority reported independence in self-care (91%) and instrumental (80%) ADL,
      but among the self-care independent, 23% reported need of personal assistance.
      Leisure disability occurred in 48% and vocational disability in 40%. Hence,
      disabilities are more common after SAH than is indicated by occurrences of motor
      and language impairments. It is concluded that the discrepancy between the
      prevalences of impairments and of disabilities may be to a great extent caused by
      coping difficulties in relation to socio-demographic and geographic
      circumstances. The findings indicate a need for rehabilitative follow-up for
      virtually all SAH-patients.

PMID- 1382452
TI  - Synthetic peptides as vaccines.
AB  - The use of synthetic peptides as an alternative approach to vaccination is
      currently being pursued. This is particularly true for viral and parasitic
      diseases in which no vaccines are yet available, most notably the acquired immune
      deficiency syndrome.

PMID- 1382453
TI  - Possible toxicity associated with L-697,661 administration in a patient with
      AIDS.

PMID- 1382454
TI  - DNA quantitation with a benchtop fluorometer.

PMID- 1382455
TI  - A histologic study of nonmorphogenetic forms of hereditary hearing impairment.
AB  - It appears that many forms of syndromic and nonsyndromic hereditary hearing
      impairment are secondary to either neuroepithelial or cochleosaccular
      dysfunction. Making this distinction can be difficult in human temporal bone
      specimens; however, this added knowledge may ultimately provide prognostic and
      therapeutic information in hearing habilitation. Fundamental studies using animal
      models of different types of hereditary deafness may also prove useful in this
      respect.

PMID- 1382456
TI  - [Proposal for a nutritional study using a survey of anthropometric data on school
      age children from the Molise countryside].
AB  - The present work is a preliminary study, preceding a larger one in the Molise
      countryside ; its aim is to set out methodological and operative basis to
      estimate the nutrition state of children aged 6-10 years, through a survey of
      anthropometric data. The list of considered parameters is here related. From the
      analysis of the different parameters it comes out that the tested population
      shows a trend to have a body weight too high compared to its height. That
      involves a more thick-set and less long-limbed body structure. Although the
      sample is small in number, the results enable us to believe that carrying on the
      study on a vast scale is suitable.

PMID- 1382457
TI  - High level expression on a chimeric anti-ganglioside GD2 antibody: genomic kappa
      sequences improve expression in COS and CHO cells.
AB  - We report a flexible strategy for the high level expression of a recombinant
      human monoclonal antibody (mAb) in Chinese hamster ovary (CHO) cells, initially
      using COS monkey kidney cell transfections to evaluate rapidly modifications to
      immunoglobulin (Ig) DNA constructs. Using sequential transfections with two
      amplifiable markers, we generated CHO cell lines and clones that secrete 80-110
      micrograms/10(6) cells/24 hours of a mouse-human chimeric IgG1 kappa mAb. This
      cellular productivity is considerably greater than most murine hybridomas and
      transfected myelomas. Our data also demonstrate that genomic kappa sequences can
      improve mAb expression in COS and CHO cells. As a paradigm, we focused our
      expression studies on a human chimeric form of 3F8, a murine mAb that binds to
      ganglioside GD2 on neuroblastoma and melanoma tumor cells.

PMID- 1382458
TI  - Growth and production kinetics of human x mouse and mouse hybridoma cells at
      reduced temperature and serum content.
AB  - The growth and production kinetics of a mouse hybridoma cell line and a human
      mouse heterohybridoma were analyzed under conditions of reduced temperature and
      serum content. The mouse hybridoma P24 had a constant cell specific production
      rate and RNA content, while the heterohybridoma 3D6-LC4 showed growth associated
      production kinetics and an increased RNA content at higher growth rates. This
      behaviour of 3D6-LC4 cells can be explained by the unusual cell cycle kinetics of
      this line, which can be arrested in any phase under growth limiting conditions,
      so that a low growth rate does not result in a greater portion of high producing
      G1-phase cells. Substrate limitation changes the cell cycle distribution of this
      cell line to a greater extent than low temperature or serum content, which
      indicates that this stress factor exerts a greater physiological control than
      assumed.

PMID- 1382459
TI  - Mathematical modelling and simulation of a recycle dialysis membrane reactor in a
      reversed micellar system.
AB  - A mathematical framework was developed for the evaluation of a recycle dialysis
      membrane reactor (RDMR). The lipase-catalyzed hydrolysis of olive oil in an AOT
      iso-octane reversed micellar system was employed as a model. Three specific
      operational strategies have been considered, namely batch, fed-batch, and fed
      batch--bleed. Simulation shows the conversion of substrate to be strongly
      dependent on efficient use of the substrate, since the permeability coefficients
      of both substrate and product are quite similar. Sensitivity analyses were
      performed to assess the influences of various parameters (membrane area,
      substrate feed rate, solvent bleed rate and permeability) on the performance of
      the reactor in different modes of operation. The analyses presented are useful to
      assist the optimization of the operational strategy used for the RDMR system.

PMID- 1382460
TI  - Surfactant interference on lipase catalysed reactions in microemulsions.
AB  - The hydrolysis of palm oil with lipase as a catalyst was carried out in two
      different microemulsion systems. One system was based on a nonionic surfactant,
      pentaethylene glycol monododecyl ether (C12EO5) and the other system was based on
      an anionic surfactant, sodium bis(2-ethylhexyl)sulphosuccinate (AOT). The yield
      of free fatty acid produced by the reaction was found to be much lower in the
      C12EO5 system compared to the AOT system. Radiochromatography showed that the low
      yield was due to enzymatic esterification on the nonionic surfactant. Kinetic
      measurements showed that the reaction rate is about ten times faster in the AOT
      based microemulsion than in the nonionic system. Differences in the microemulsion
      structure and interfacial tensions in the two systems were found to be of no
      significant importance for explaining this difference. Kinetic data of mixed
      surfactant microemulsions indicated that the observed difference in the reaction
      rates of the AOT and the C12EO5 microemulsion systems was a consequence of the
      C12EO5 surfactant competing with the substrate for the active site of the enzyme.
      The reason why C12EO5 surfactant inhibited the reaction, and AOT surfactant did
      not, was found to be related to differences in the structures of the hydrophobic
      part of the surfactant.

PMID- 1382461
TI  - Hepatitis C virus antibodies and hepatitis C virus RNA in Chinese blood donors
      determined by ELISA, recombinant immunoblot assay and polymerase chain reaction.
AB  - Antibodies to hepatitis C virus (anti-HCV) were determined in Chinese blood
      donors from the city of Wuhan by a second generation ELISA screening test and a
      confirmatory recombinant immunoblot assay (RIBA II). Two materials of 281 and 222
      sera were sampled under similar conditions in 1989 and 1990, respectively. The
      first collection of sera was sent to Sweden in lyophilized form, the second
      directly as fresh unfrozen sera. A high proportion (7.1%) of the lyophilized sera
      reacted positively in the anti-HCV screening assay, but only seven (2.5%) were
      positive by the RIBA confirmatory test. In four of these sera HCV-RNA could be
      detected by polymerase chain reaction (PCR) analysis. In the second material of
      fresh sera six reacted positively in the screening anti-HCV ELISA, but only one
      was RIBA positive and four were RIBA indeterminate. None of these sera was
      positive for HCV-RNA. Thus, the overall prevalence of anti-HCV among the 503
      Chinese blood donors, as identified by RIBA, was 1.6%, and of HCV-RNA by PCR
      0.8%. The confirmed antibody prevalence is higher than reported from the Western
      world. Caution about using data from the screening ELISA only, especially if sera
      have been handled in an unorthodox way, is emphasized.

PMID- 1382462
TI  - Long-term psychological consequences of childhood frontal lobe lesion in patient
      DT.
AB  - Patient DT was examined 26 years after she acquired focal frontal lobe damage at
      7 years of age. This report focused on several aspects of psychological outcome,
      including the empirical study of social development into early adulthood.
      Standardized measures of empathy, psychosocial development, and personality were
      analyzed, along with a moral judgment interview and patterns of adult social
      behavior. Results indicated that DT has a very limited capacity for empathic
      understanding, inadequate identity development, difficulties in vocational
      adjustment, and a concrete level of moral reasoning. Her social behavior and
      profile of test scores suggest that social development and adaptation have been
      arrested at early adolescent levels. We conclude that early frontal lobe damage
      has profound effects on social development, and that the frontal lobes provide a
      crucial neural substrate for social maturation.

PMID- 1382463
TI  - Developmental impact of frontal lobe injury in middle childhood.
AB  - Executive function of frontal lobe systems, like intelligent behavior, appears to
      demonstrate two major features: it is adaptive and goal-directed. Disruption of
      executive function following injury to the frontal lobes in childhood might be
      predicted to impact the trajectory of normal cognitive, behavioral, and social
      development. Case studies of two children injured at different ages showed the
      primary developmental impact to involve the behavioral and social realms. While
      cognitive development may be suspected to also be considerably influenced,
      assessment of changes in cognitive abilities by traditional psychometric means
      was found to be problematic. Psychometric changes were found to occur over a
      prolonged period of time, emphasizing the importance of documenting observations
      and chronicling postinjury events.

PMID- 1382464
TI  - Single-stranded DNA binding protein facilitates amplification of genomic
      sequences by PCR.

PMID- 1382465
TI  - The oocyte nucleus isolated in oil retains in vivo structure and functions.
AB  - We describe a technique for isolating the nucleus of the giant amphibian oocyte
      under paraffin oil. The method precludes the losses of small solutes and proteins
      that accompany isolation of nuclei into aqueous media. An individual oocyte is
      blotted, placed under oil, punctured near the animal pole and then squeezed to
      gently extrude the nucleus into the oil, thereby avoiding exposure to any aqueous
      environment. Light and electron microscopy of the oil-isolated nucleus
      demonstrate that its in vivo morphology is preserved. We also describe techniques
      that facilitate the study of nuclear functions under oil. Oil-isolated oocyte
      nuclei retain many in vivo functions for several hours, including size-selective
      envelope permeability, RNA synthesis and the ability to break down in response to
      cdc2/cyclin meiotic maturation promoting factor.

PMID- 1382466
TI  - In search of retrotransposons: exploring the potential of the PCR.
AB  - A rapid and universal procedure for isolating reverse transcriptase encoding
      elements from diverse mammalian genomes using PCR is described. We have designed
      short, degenerate primers to conserved amino acid domains of retroviral reverse
      transcriptase. These primers amplify a region, predicted to be 342-396 base pairs
      for most mammalian retroviruses, that spans several conserved domains of reverse
      transcriptase. The region encoded by the amplified PCR product contains a number
      of highly conserved amino acids that aid in identification of either degenerate
      reverse transcriptase or reverse transcriptase from new, undescribed elements.
      Additionally, these primers allow the amplification of a piece of DNA large
      enough to be used for phylogenetic analysis. The primers have been used
      successfully to isolate a region of three related reverse transcriptases from two
      mammalian taxa. The generality of this approach is discussed.

PMID- 1382467
TI  - An alternative staining procedure for detecting proteins in an agarose gel.

PMID- 1382468
TI  - Utility of internal markers to improve the accuracy of cystic fibrosis genotype
      analysis.
AB  - DNA diagnostic tests often utilize restriction endonuclease digestion of PCR
      amplified portions of genes under analysis. When partial digestion occurs, the
      resulting patterns may lead to error in diagnosis. To overcome such potential
      errors in cystic fibrosis testing, we have developed internal markers that can
      increase the precision and reliability of genotype assignments.

PMID- 1382469
TI  - A nonradioactive micro-assay for released reverse transcriptase activity of a
      lentivirus.
AB  - A nonradioactive micro-assay procedure for detection of released reverse
      transcriptase activity from cells infected with equine infectious anemia virus is
      described. This procedure utilizes biotinylated-dUTP in conjunction with a
      streptavidin-alkaline phosphatase conjugate. Detection of alkaline phosphatase is
      by autoradiography of the chemiluminescence produced during enzymatic
      dephosphorylation of Lumi Phos 530. This method, as with reverse transcriptase
      micro-assays employing 32P-labeled nucleotides, is suited to the processing of
      numerous samples, while having the advantages of safety and stability normally
      associated with nonradioactive methods of detection. Sensitivity is comparable to
      a reverse transcriptase micro-assay using 32P-dTTP.

PMID- 1382470
TI  - The use of synthetic peptide combinatorial libraries for the identification of
      bioactive peptides.
AB  - The systematic preparation of synthetic peptide combinatorial libraries (SPCLs),
      each composed of tens of millions of peptides that can be screened in existing
      diagnostically or pharmacologically relevant in vitro assay systems, is reviewed.
      The identification of optimal peptide sequences has been achieved through the
      screening in solution of SPCLs, each element of which is composed of more than
      100,000 nonsupport-bound peptides in equimolar representation, along with an
      iterative synthesis and screening process. Examples are presented in which an
      SPCL, composed in total of 52,128,400 acetylated hexa-peptides, is used along
      with an iterative selection process to precisely identify the antigenic
      determinant of a peptide recognized by a monoclonal antibody using competitive
      enzyme-linked immunosorbent assay. This same library was also used to develop
      highly potent antimicrobial peptides in bacterial growth inhibition assays. A
      separate non-acetylated SPCL was used to screen and identify high affinity
      peptide ligands using an opiate radio-receptor binding assay.

PMID- 1382471
TI  - Preferential expression of the Drosophila rutabaga gene in mushroom bodies,
      neural centers for learning in insects.
AB  - Seven lines were isolated with P element insertions in the cytogenetic vicinity
      of the learning and memory gene, rutabaga, from an enhancer detector screen
      designed to mark genes preferentially expressed in mushroom bodies. Six of these
      lines performed poorly in learning and memory tests, and several failed to
      complement an existing rutabaga allele. Molecular cloning revealed that the P
      elements were inserted in the putative promoter of the rutabaga gene. RNA in situ
      hybridization and immunohistochemistry demonstrated that the expression of the
      rutabaga gene, which encodes a Ca2+/calmodulin-responsive adenylyl cyclase, is
      markedly elevated in the mushroom bodies of normal flies and that the insertion
      elements compromised its expression in the new rutabaga mutants. The reisolation
      of a known learning and memory gene, but with a heretofore unknown expression
      pattern, strongly supports the postulate that mushroom bodies are principal sites
      mediating olfactory learning and memory.

PMID- 1382472
TI  - Role of the floor plate in axonal patterning in the zebrafish CNS.
AB  - To determine the role of the floor plate (FP) in CNS development, I have used
      labeling techniques, including immunolabeling, to analyze cyclops mutant embryos,
      which lack the FP. Except for the anterior brain, the mutant phenotype is almost
      exclusively confined to the vicinity of the ventral CNS midline. In the midbrain,
      the number of ventral neurons is reduced and cell patterning is disturbed. In
      contrast, the neuronal arrangement in the spinal cord is almost normal, including
      in particular both primary and secondary motoneurons. Longitudinal axonal bundles
      are disorganized in both the brain and spinal cord. Laser ablating the FP in wild
      type embryos locally phenocopies cyclops axonal disturbances, and transplanting
      wild-type FP precursor cells into mutants locally rescues the disturbances. These
      results demonstrate a significant role for the FP in pathfinding and
      fasciculation by axons in situ, especially during their longitudinal courses.

PMID- 1382473
TI  - PC12 cell neuronal differentiation is associated with prolonged p21ras activity
      and consequent prolonged ERK activity.
AB  - Expression of oncogenic ras in PC12 cells causes neuronal differentiation and
      sustained protein tyrosine phosphorylation and activity of extracellular signal
      regulated kinases (ERKs), p42erk2 and p44erk1. Oncogenic N-ras-induced neuronal
      differentiation is inhibited by compounds that block ERK protein tyrosine
      phosphorylation or ERK activity, indicating that ERKs are not only activated by
      p21ras but serve as the primary downstream effectors of p21ras. Treatment of PC12
      cells with nerve growth factor or fibroblast growth factor results in neuronal
      differentiation and in a sustained elevation of p21ras activity, of ERK activity,
      and of ERK tyrosine phosphorylation. Epidermal growth factor, which does not
      cause neuronal differentiation, stimulates only transient (< 1 hr) activation of
      p21ras and ERKs. These data indicate that transient activation of p21ras and,
      consequently, ERKs is not sufficient for induction of neuronal differentiation.
      Prolonged ERK activity is required: a consequence of sustained activation of
      p21ras by the growth factor receptor protein tyrosine kinase.

PMID- 1382474
TI  - Protein phosphatases modulate the apparent agonist affinity of the light
      regulated ion channel in retinal rods.
AB  - Ion channels directly activated by cGMP mediate the light response in retinal
      rods. Several components of the enzyme cascade controlling cGMP concentration are
      regulated, but there are no accepted mechanisms for modulation of the response of
      the channel to cGMP. Here we report evidence that in excised patches an
      endogenous protein phosphatase converts the channel from a state with low cGMP
      sensitivity to a state with almost 3 orders of magnitude higher sensitivity in
      the predicted physiological range of cGMP concentration. The action of this
      endogenous phosphatase was blocked by specific serine/threonine phosphatase
      inhibitors (microcystin-LR, okadaic acid, and calyculin A). An increase in
      apparent agonist affinity also was produced by addition of purified protein
      phosphatase 1. In contrast, protein phosphatase 2A decreased apparent agonist
      affinity, suggesting that two phosphorylation sites may regulate the agonist
      sensitivity of the channel in a reciprocal manner. This regulation may be
      involved in fine-tuning the light response or in light or dark adaptation.

PMID- 1382475
TI  - Activation of phosphatidylinositol-3 kinase by nerve growth factor involves
      indirect coupling of the trk proto-oncogene with src homology 2 domains.
AB  - Growth factor receptor tyrosine kinases can form stable associations with
      intracellular proteins that contain src homology (SH) 2 domains, including the
      p85 regulatory subunit of phosphatidylinositol (PI)-3 kinase. The activation of
      this enzyme by growth factors is evaluated in PC12 pheochromocytoma cells and NIH
      3T3 fibroblasts expressing the pp140c-trk nerve growth factor (NGF) receptor (3T3
      c-trk). NGF causes the rapid stimulation of PI-3 kinase activity detected in anti
      phosphotyrosine, but not in anti-trk, immunoprecipitates. This effect coincides
      with the tyrosine phosphorylation of two proteins, with molecular masses of of
      100 kd and 110 kd, that coimmunoprecipitate with p85. Similar phosphorylation
      patterns are induced when an immobilized fusion protein containing the amino
      terminal SH2 domain of p85 is used to precipitate tyrosine-phosphorylated
      proteins. Thus, although NGF produces the rapid activation of PI-3 kinase through
      a mechanism that involves tyrosine phosphorylation, there is no evidence for
      tyrosine phosphorylation of p85, or for its ligand-dependent association with the
      NGF receptor. Perhaps another phosphoprotein may link the NGF receptor to this
      enzyme.

PMID- 1382476
TI  - Comparison of pregnancy rates following gamete intrafallopian transfer (GIFT)
      under general anesthesia with thiopental sodium or propofol.
AB  - STUDY OBJECTIVE: To determine whether the pregnancy rate for gamete
      intrafallopian transfer (GIFT) patients who received thiopental sodium was
      different from the pregnancy rate for patients who received propofol for the
      induction of general anesthesia. DESIGN: Retrospective review of clinical
      records. SETTING: Private outpatient infertility clinic. PATIENTS: Two hundred
      eighty-two consecutive GIFT procedures performed on 230 patients with
      infertility. INTERVENTION: Patients undergoing GIFT were divided into two groups
      on the basis of whether they received thiopental or propofol for induction of
      anesthesia. MEASUREMENTS AND MAIN RESULTS: Clinical pregnancy following each GIFT
      procedure was assessed by multiple-serum beta human chorionic gonadotropin and
      ultrasound determinations. The pregnancy rates of 24.6% and 25.8% for the
      thiopental and propofol groups, respectively, were not significantly different.
      CONCLUSIONS: The pregnancy rate following GIFT for patients given propofol for
      induction of general anesthesia did not differ from that for patients given
      thiopental.

PMID- 1382477
TI  - Human lung mast cells and pulmonary macrophages produce tumor necrosis factor
      alpha in sensitized lung tissue after IgE receptor triggering.
AB  - Tumor necrosis factor (TNF) is considered to play a key role in the pathogenesis
      of allergic disorders. We examined TNF production in human lung fragments after
      IgE receptor triggering at mRNA and protein levels. IgE receptor triggering was
      performed by sensitizing lung fragments with monoclonal human IgE and then
      exposing them to anti-human IgE antibody. Cytotoxic activity against L929 cells
      appeared in the culture supernatant of lung fragments 2 h after IgE receptor
      triggering and increased for up to 4 h. This cytotoxic activity was completely
      neutralized by anti-human TNF antibody. Northern blot analysis demonstrated that
      1.8-kb TNF mRNA transcripts in sensitized lung fragments were expressed as early
      as 1 h after IgE receptor triggering and continued up to 4 h. Immunohistochemical
      analysis revealed TNF localization in tissue mast cells, alveolar macrophages,
      tissue macrophages, and bronchial epithelial cells. Double staining with anti-TNF
      antibody and alcian blue clearly identified that lung mast cells are one of the
      TNF-positive cell types in the pulmonary tissue. With immunoelectron microscopy,
      TNF immunoreactivity was detected in the rough endoplasmic reticulum and the
      perinuclear spaces in tissue macrophages, and in the cytosol and the perinuclear
      spaces in bronchial epithelial cells. In addition, IgE was detected on the cell
      surface of mast cells, tissue macrophages, and alveolar macrophages. These
      results suggest that TNF is released from mast cells and pulmonary macrophages
      through IgE receptor triggering and may play a key role in the allergic reaction
      in human airway.

PMID- 1382478
TI  - The expression of leukocyte-endothelial adhesion molecules is increased in
      perennial allergic rhinitis.
AB  - Accumulating evidence supports the importance of leukocyte-endothelial cell
      adhesion molecule (CAM) expression as an initiating process in tissue
      inflammation. To investigate the relevance of CAM expression to allergic airways
      inflammation, nasal biopsies from patients with perennial allergic rhinitis (n =
      8) and from nonatopic healthy volunteers (n = 8) were immunostained with
      monoclonal antibodies directed against the CAMs, intercellular adhesion molecule
      1 (ICAM-1), endothelial cell adhesion molecule-1 (ELAM-1), and vascular cell
      adhesion molecule-1 (VCAM-1). The endothelial staining of these CAMs was related
      to the number of vessels within each biopsy, delineated by a monoclonal antibody
      against Ulex europaeus-1 lectin bound to endothelial cells, and to the number of
      tissue leukocytes staining for one of the ligands of ICAM-1, the beta 2 integrin,
      lymphocyte function-associated antigen (LFA-1). Expression of CAMs was related to
      the number of infiltrating neutrophils, eosinophils, and lymphocytes identified
      immunohistochemically within the biopsies. ICAM-1 was the most prominent CAM
      present on the endothelium of the normal nasal mucosa, with less expression of
      ELAM-1 and only minimal or absent expression of VCAM-1. In perennial rhinitis,
      both ICAM-1 (P less than 0.05) and VCAM-1 (P less than 0.01) expression on
      endothelial cells were increased and were positively correlated in their level of
      expression (P less than 0.002). The number of tissue LFA-1-positive cells was
      significantly greater (P less than 0.05) in the biopsies from the perennial
      rhinitics (median, 27.3/mm2) than from the healthy controls (median, 5.3
      cells/mm2). LFA-1 expression significantly correlated with the number of ICAM-1
      positive vessels (P less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382479
TI  - Interleukin-8 and RANTES inhibit basophil histamine release induced with monocyte
      chemotactic and activating factor/monocyte chemoattractant peptide-1 and
      histamine releasing factor.
AB  - The objective of this study was to investigate the effect of interleukin-8 (IL-8)
      and RANTES on basophil histamine release induced with monocyte chemoattractant
      peptide-1 (MCP-1) and crude histamine releasing factor (HRF). IL-8 induced low
      levels of histamine release (8.5 +/- 0.5%) from basophils obtained from only six
      of 20 donors at high concentrations (10(-6) M). RANTES induced histamine release
      (16 +/- 2%) from basophils of four of 15 donors at 10(-7) M concentration.
      However, both IL-8 and RANTES inhibited MCP-1 and HRF-induced histamine release
      from basophils dose-dependently at concentrations of 10(-9) to 10(-7) M.
      Basophils from all donors showed a significant inhibitory response (greater than
      15%). The maximal inhibition of MCP-1 and HRF by IL-8 was 28 +/- 4% and 48 +/-
      8%, respectively. The maximal inhibition of MCP-1 and HRF by RANTES was 26 +/- 4%
      and 43 +/- 6%, respectively. Peripheral blood mononuclear cell-derived HRF was
      purified into three distinct peaks by reverse-phase high performance liquid
      chromatography. Peak I contained MCP-1 as judged by binding to an immunoaffinity
      column that was prepared with anti-MCP-1 antibody. IL-8 inhibited histamine
      release induced with all three peaks of HRF. The inhibition of histamine release
      by IL-8 was significantly higher in normal subjects than in allergic patients (59
      +/- 9% versus 31 +/- 7%, P less than 0.05). Both IL-8 and RANTES inhibited
      cytokine-induced histamine release only and did not affect histamine release by
      anti-IgE, FMLP, and C5a.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382480
TI  - The effect of T-cell depletion on enhanced basophil histamine release after in
      vitro incubation with live influenza A virus.
AB  - A number of mechanisms participate in virus-induced asthma. Previously, we
      described enhanced basophil histamine release (HR) during an experimentally
      induced rhinovirus infection and after in vitro incubation of peripheral blood
      mononuclear cells (PBMC) with influenza virus. This study extends our previous
      observations and examines the effect of influenza A virus on basophil leukotriene
      C4 (LTC4) release as well as the effect of T-cell depletion on virus-enhanced
      basophil HR. PBMC were isolated from ragweed-allergic subjects and incubated with
      live influenza A virus or control medium (allantoic fluid). After incubation with
      influenza A, ragweed antigen (AgE) stimulated LTC4 and HR were enhanced (P less
      than 0.05). To further define the role of T cells in virus-enhanced basophil
      secretion, PBMC were isolated and divided into two aliquots. In one aliquot, T
      cells were removed by magnetic bead separation of mouse monoclonal anti-CD3
      coated lymphocytes. T-cell-depleted and nontreated PBMC suspensions were
      incubated with influenza A or control medium, collected, and challenged with AgE
      to release histamine. Basophil HR was enhanced in the virus-treated group of PBMC
      that had not undergone T-cell depletion. In contrast, virus incubation did not
      enhance HR in the T-cell-depleted fraction. Finally, preliminary analysis of the
      supernate from virus-treated leukocytes indicates the presence of interferon
      gamma. These findings suggest that T cells, and their cytokine products, play an
      integral role in the process by which viruses enhance basophil HR.

PMID- 1382482
TI  - Granulocyte colony-stimulating factor: structure, function and physiology.

PMID- 1382481
TI  - Contrast transesophageal echocardiographic demonstration of coronary artery
      fistula within left atrial appendage thrombus in mitral stenosis.
AB  - Coronary neovascularization and fistula formation arising from the left
      circumflex artery demonstrated by coronary angiography is a specific sign for the
      presence of left atrial appendage thrombus in patients with mitral stenosis.
      However, the fistula drainage site in the left atrium in relation to the thrombus
      cannot be ascertained by the angiographic method. We performed transesophageal
      echocardiography simultaneously with coronary angiography in five patients with
      severe mitral stenosis and left atrial appendage thrombus. The angiography showed
      coronary neovascularization and fistula arising from the left circumflex artery
      in three patients. In these three patients, the transesophageal echocardiography
      confirmed the presence of a coronary fistula by identifying contrast exuding from
      the surface of the thrombus. Thus we have shown for the first time the usefulness
      of contrast transesophageal echocardiography in imaging the exact drainage site
      of coronary artery fistula from left atrial appendage thrombus.

PMID- 1382483
TI  - Clinical applications of granulocyte colony stimulating factor (G-CSF).

PMID- 1382484
TI  - Large systemic collateral arteries developing late after total repair of
      tetralogy of Fallot.
AB  - A 22-year-old man with tetralogy of Fallot successfully underwent a corrective
      operation. Twenty years after total correction, large systemic collateral
      arteries (SCA) developed. The SCA arose from the right subclavian and internal
      mammary arteries. The SCA were not present at the time of total repair and
      thoracotomy had not been performed on this side. A closed-tube thoracostomy for
      postoperative pneumothorax may be responsible for the development of the large
      SCA.

PMID- 1382485
TI  - [Effectiveness of early stimulation in the mentally handicapped or at-risk
      child].

PMID- 1382486
TI  - [Alterations in neuro-development in the 1st year of life in newborn infants
      weighing 2000 grams or less at birth].
AB  - The infants with low weight at birth have great chance of exhibiting early death
      or neurodevelopmental sequelae. We prospectively evaluated the neurological and
      psychological development during the first year of life in 118 infants who
      weighted less than 2,000 g at birth. All patients were examined with the Amiel
      Tison and Grenier test (neurologic evaluation), Gesell test (psychological) and
      Brunette-Lezine test (Psychomotor scale). Mean gestational age was 33 weeks (SD =
      3.1) and birth mean weight was 1495 g (SD = 291). Seventy per cent were delivered
      by cesarean section. Neurological abnormalities were found in 20 infants
      (alteration of muscular tone in all and motor deficit in 50%). Twenty five per
      cent had abnormal Gesell test and 17% psychomotor retardation (13% mild and 4%
      severe).

PMID- 1382487
TI  - Recent development of anti-allergic drugs.

PMID- 1382488
TI  - Drug treatment for allergic rhinitis: a clinical immunologist's view.

PMID- 1382489
TI  - Ultrahigh-resolution scanning electron microscopy and its application to medical
      researches.
AB  - By the development of an ultrahigh-resolution SEM, the resolution of SEM was
      markedly improved. Concerning specimen preparation, the osmium-DMSO-osmium
      method, which is effective for revealing intracellular structures, and the carbon
      plate method for observing smaller objects such as viruses and biological
      macromolecules were devised in recent years. With the improvement of instrumental
      resolution and specimen preparation techniques, the SEM has become a powerful
      tool for studying ultrastructure in biomedicine.

PMID- 1382490
TI  - The effectiveness of early intervention: a critical review.
AB  - The following principles are now clearly defined in the management of children
      with developmental delay: (1) Multidisciplinary teams are more effective than
      individual therapeutic approaches. (2) The whole development of the child needs
      to be considered rather than a single deficient area alone. (3) Home-based
      programmes are more effective in the young preschool child than centre-based
      programmes alone. (4) Parent involvement in partnership with professionals is
      essential for sustained progress. (5) Maximum effectiveness is achieved when
      parental skills are increased. (6) Programmes commencing earlier in preschool
      years are more effective than those that commence late. This concept has been
      recently challenged and evidence supports benefits for the disadvantaged rather
      than the disabled. White also contends that there is 'simply not enough
      information to be confident about the long-term impact of early intervention with
      handicapped children and evidence in support of many of the commonly held
      positions about mediating variables (e.g. parental involvement, age at start) is
      either non-existent or contradictory. Early intervention is clearly effective in
      offering parental support, fostering parent/child relationships and diminishing
      anxiety even for those programmes that have not at present been proven in
      altering the developmental disability. Programmes that involve high cost, disrupt
      total family functioning, deflect scarce resources away from more proven areas of
      effectiveness should be discouraged, and they should never cause guilt in either
      parent or professional when they seem ineffective. Future research should include
      investigation of outcomes other than cognitive and physical functioning alone. We
      should be warned from the somewhat crisp statement of Mark Twain: 'There is
      something fascinating about science. One gets such wholesale returns of
      conjecture out of such a trifling investment in fact'.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382491
TI  - Immunorecognition of ganglioside epitopes: correlation between affinity and
      cytotoxicity of ganglioside antibodies.
AB  - Cell-surface gangliosides have immunomodulatory effects that are presumed to play
      a role in tumour growth, progression, metastasis and therapy. To study the
      epitopes of gangliosides on human malignant melanomas and to search for
      monoclonal antibodies (Mabs) with superior immunological effector functions, 19
      ganglioside antibodies were established. Specificity and affinity of nine
      antibodies of IgG3 isotype were evaluated by enzyme linked immunosorbent assay
      and thin layer chromatography with a panel of purified gangliosides. All
      antibodies recognised the ganglioside GD3, but their epitope specificity divided
      them into five groups. Their affinity constants for ganglioside GD3 ranged from
      4.7 x 10(6) to 2.3 x 10(8), with 2 x 10(7) for Mab R-24. Two antibodies possessed
      a higher affinity for GD2 than for GD3. The functional properties of the
      antibodies were investigated in vitro. Differences in the degree of tumour lysis
      by complement fixation correlated with the affinity constants. Every ganglioside
      antibody differed in epitope recognition, affinity and cytotoxicity. Therefore
      some of these antibodies might even be more useful in the immunotherapy of
      malignant melanoma than Mab R-24.

PMID- 1382492
TI  - Octreotide and interferon alfa: a new combination for the treatment of malignant
      carcinoid tumours.
AB  - 24 patients with malignant carcinoid tumours received octreotide and interferon
      alfa (IFN-alpha). All the patients initially received octreotide 50-100
      micrograms, twice daily. When progressive symptoms or increasing biochemical
      markers were observed, the daily dose was raised to a median 300 micrograms. If
      the initial dose proved ineffective or if no improvement was seen after
      escalation, IFN-alpha was added (median 9 MU subcutaneously per week). After the
      addition of IFN-alpha, 17 of the 22 patients (77%) with elevated urinary 5
      hydroxyindoleacetic acid showed a significant (> 50%) reduction. Only 1 patient
      progressed and 4 had continuously stable biochemical disease. No significant
      reduction in tumour size was noted; in 5 patients, the tumour continued to grow
      despite decreasing hormone levels. 18 patients had carcinoid syndrome when IFN
      alpha was added in 10 (56%) symptoms ameliorated. Thus, the addition of IFN-alpha
      is beneficial for patients with malignant carcinoid tumours that progress and/or
      who do not respond to octreotide.

PMID- 1382493
TI  - Treatment of metastatic carcinoid tumour with recombinant interferon alfa.
AB  - 14 patients with metastatic carcinoid tumour were treated with recombinant
      interferon alfa 6-30 x 10(6) IU weekly for 3-25 (median 6.5) months. A decrease
      in the 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) level to less than 50% of
      the pretreatment value was observed in 5 of the 10 cases with an elevated urinary
      5-HIAA level. In 4 of the 5 remaining patients, the 5-HIAA level decreased 30-50%
      from the pretreatment value. 5 of the 9 evaluable patients with carcinoid
      syndrome experienced symptomatic relief, but none became symptom-free. Severe
      toxicity was not observed. The median time to progression was 4.5 months, and, in
      patients with a greater than 50% decrease in 24-h urinary-5-HIAA, it was 17
      months. Objective regression in tumour size could not be demonstrated in any of
      the patients.

PMID- 1382494
TI  - Antitumour effect and symptomatic control with interferon alpha 2b in patients
      with endocrine active tumours.
AB  - 26 patients with progressive neuroendocrine tumours received 3 x 10(6)U/m2
      interferon alfa (IFN-alpha 2b) subcutaneously thrice weekly, until progression,
      as outpatients with moderate toxicity. 4/16 carcinoids and none out of 10
      endocrine pancreatic tumours showed objective regression. Another 17 patients
      (68%) had no change. For a median of 34 weeks symptom control was excellent: 9 of
      17 patients had major relief from pain, 11 of 13 from diarrhoea, and 7 of 7 from
      flushing. Thus, low-dose INF-alpha 2b given thrice weekly might be as effective
      as daily treatment with higher dosages. Treatment was only administered to
      patients with progression or major symptoms and this did not seem to adversely
      affect remission quality and survival.

PMID- 1382495
TI  - ABEP as primary chemotherapy for Hodgkin's disease.
AB  - 20 untreated Hodgkin's disease patients and 1 patient relapsing after
      radiotherapy (17 stage IIB-IV and 4 stage I-IIA) were given doxorubicin,
      bleomycin, etoposide and prednisone on a 21-day cycle. The response rate was 95%
      and 16 patients (76%) achieved complete remission. 4 patients have relapsed 2, 5,
      22 and 50 months after treatment. Survival was 100% at a median follow-up of 35
      months. However, due to dyspnoea on exertion in 2 patients, bleomycin will be
      abandoned, and the occurrence of two second malignancies questions the role of
      etoposide as a leukaemogenic agent.

PMID- 1382496
TI  - Clinical oncology: case presentations from oncology centres. Intensive treatment
      of poor prognosis gastrointestinal lymphoma.

PMID- 1382497
TI  - Progress, problems and priorities in quality of life research.
AB  - Considerable progress has been made in the methodology of quality of life
      research and we now need to judge the clinical utility of this approach in
      clinical trials. Some of the logistic problems in implementing these studies are
      formidable, however, and this has contributed to a slow uptake of quality of life
      research in clinical practice. Pragmatic guidelines are now needed to help
      overcome problems of implementation and analysis. Further adaptation and
      refinement of instruments will be needed to meet new challenges in the field, but
      we must be selective in our research initiatives and ensure that quality of life
      becomes translated into improved patient care.

PMID- 1382498
TI  - Mediastinal non-seminomatous germ cell tumours: effectiveness of platinum,
      etoposide, bleomycin combination chemotherapy plus adjunctive surgery.

PMID- 1382499
TI  - Alternating chemo-radiotherapy with cisplatin and 5-fluorouracil plus bleomycin
      by continuous infusion for locally advanced undifferentiated carcinoma
      nasopharyngeal type.
AB  - More than 80% of undifferentiated carcinoma nasopharyngeal type patients with N3
      disease (AJC-UICC 1987) will die with or from distant metastases within 3 years
      after the first symptom. From February 1986 to November 1987 30 consecutive
      patients with very advanced local disease were entered in a programme with
      chemotherapy-radiotherapy (CT-RT) alternation after a thorough work-up to
      eliminate the possibility of distant metastases. PROTOCOL: two cycles of
      cisplatin 100 mg/m2 day 1, bleomycin 15 mg intravenously day 1 and 16 mg/m2 per
      day by continuous infusion days 1-5; 5-fluorouracil (5-FU) 650 mg/m2 per day by
      continuous infusion days 1-5 4 weeks apart. This was followed by two series of
      high-energy radiotherapy, 35 Gy/3.5 weeks, with a third chemotherapy cycle in
      between. 27 men and 3 women were treated, the median age was 37 years (range 17
      71) and the mean WHO performance status was 1 (range 0-3). TNM classification: 15
      T4, 9 T3, 6 T2, 28 N3 and 2 N2c. 18 patients had nodes larger than 8 cm and 24
      had bulky bilateral cervical nodes. Toxicity for this protocol was moderate,
      nausea and vomiting being the main side-effects. Results after two CT cycles were
      3 complete responses (CR; 10%), 22 partial responses (PR; 73%), 2 disease
      stabilizations, 2 progressions, and 1 patient inevaluable. Of the 30 patients, 27
      patients completed the CT-RT protocol, 2 patients died before radiotherapy and 1
      refused treatment after 2 days on protocol. 25 patients were in CR 3 months after
      the end of radiotherapy. As of August 1991, with a median follow-up of 55 months
      (range 43-63), there are 17 patients alive, 2 of them with active disease and 15
      are NED (2 after salvage therapy).

PMID- 1382500
TI  - Differential expression of insulin-like growth factor binding proteins in human
      non-small cell lung cancer cell lines.
AB  - The possible expression and secretion of insulin-like growth factor binding
      proteins (IGFBPs) by non-small cell lung cancer (NSCLC) cell lines was
      investigated and compared with possible IGFBP expression by primary NSCLC
      tumours. Cells growing under serum-free conditions released binding proteins with
      apparent molecular masses of 26-43 kD when analysed by a ligand blotting method
      under non-reducing conditions. Additionally, northern blot analysis of total RNA
      from NSCLC cell lines and tumours was performed using cDNAs coding for each of
      IGFBP-1, IGFBP-2, and IGFBP-3. This analysis revealed expression of all three
      mRNAs to varying degrees by all cell lines. In contrast all primary tumours
      analysed expressed predominantly IGFBP-2 and IGFBP-3 and none showed any evident
      expression of IGFBP-1. Both NSCLC cell lines and tumours synthesise IGFBPs but
      the pattern of expression differs significantly between cell lines and primary
      tumours.

PMID- 1382502
TI  - Failure of palliative radiotherapy in high-grade angiosarcoma of bone.

PMID- 1382501
TI  - Autocrine role of insulin-like growth factor (IGF)-I in a human thyroid cancer
      cell line.
AB  - An established cell line (TC-cell, clone 78) derived from human thyroid papillary
      cancer cells was investigated for production of peptide growth factors. The cells
      had specific binding sites for insulin-like growth factor-I (IGF-I) and responded
      to this growth factor with increased proliferation. Culture medium conditioned by
      TC cells was found to contain insulin-like growth factor (IGF)-I and IGF-binding
      protein(s). Furthermore, reverse transcription-polymerase chain reaction revealed
      expression of IGF-I mRNA. When monoclonal antibody to IGF-I receptors (alpha IR3)
      was added, the growth of TC cells cultured in serum-free medium was significantly
      reduced. The growth rate of the cells was restored when the antibody was removed
      from the medium. These results strongly suggest that TC cells produce IGF-I,
      which is involved in the regulation of their own growth.

PMID- 1382503
TI  - [Spheroid].

PMID- 1382504
TI  - An animal model for oral cancer.
AB  - Human head and neck squamous cell carcinogenesis (SCC) is a common malignancy
      that appears to be related to continuous exposure to putative carcinogens or
      promoters such as tobacco and alcohol. To understand the mechanisms of the
      development of head and neck cancer and to test the efficiency of new therapeutic
      approaches, the characterization of an animal model system is necessary. The
      check-pouch carcinogenesis model in Syrian golden hamsters is probably the best
      known animal system that is most closely comparable with the development of
      premalignant and malignant lesions in human oral cancer. Furthermore, it is one
      of the most well-characterized animal system models for SCC. Our first approach
      to understanding the cellular and molecular changes that occur in the hamster
      cheek-pouch carcinogenesis process was to compare this model to the mouse-skin
      system, in which a number of critical events have been well characterized. We
      examined the sequential expression of hyperplasia, micronucleated cells,
      ornithine decarboxylase activity, polyamine levels, transglutaminase I activity,
      epidermal growth factor receptor levels, expression of several keratins, gamma
      glutamyl transpeptidase, and nucleolar organizer regions. We suggest that these
      markers can be used to understand mechanisms of carcinogenesis and, in addition,
      can serve as alternative shorter end points in studies of chemoprevention. We
      also present preliminary molecular studies in the experimental oral model. We
      obtained a partial sequence of exon 2 of the Ha-ras gene and detected an A182---
      T transversion in codon 61 in hamster cheek-pouch SCC induced by 7,12
      dimethylbenz(a)anthracene.

PMID- 1382505
TI  - Influence of age on the relation between heart rate variability, left ventricular
      ejection fraction, frequency of ventricular extrasystoles, and sudden death after
      myocardial infarction.
AB  - AIMS: To examine the influence of age on the prediction of sudden death after
      acute myocardial infarction based on heart rate variability (HRv), left
      ventricular ejection fraction (LVEF), and the frequency of ventricular
      extrasystoles. BACKGROUND: Autonomic and left ventricular function and the
      frequency of ventricular extrasystoles change with age but the influence of age
      on the prediction of sudden death from these variables has not been examined.
      METHODS: The 477 patients who had been through an early postinfarction risk
      stratification protocol and followed up for a mean of 790 days were dichotomised
      at 60 years of age. RESULTS: Sudden deaths occurred with similar frequency in
      both age groups (12 (4.7%) of the 256 patients aged < 60 years and seven (3.2%)
      of the 221 older patients). Sudden death, however, accounted for 52% of all
      deaths in the young group but only 18.4% of all deaths in the older group (p <
      0.01). An HRv index of < 20 units combined with an average of more than 10
      ventricular extrasystoles an hour on Holter monitoring (VE10) had a sensitivity
      of 50%, a positive predictive accuracy of 33%, and a risk ratio of 18 in the
      young group (p < 0.001) but was not significantly predictive in older patients.
      The situation was similar when the combination of an LVEF < 40% with VE10 was
      considered. This combination had a sensitivity of 44%, positive predictive
      accuracy of 36.4%, and a risk ratio of 16.1 in young patients (p < 0.001), but
      was not significantly predictive in older patients. The combination of VE10 with
      either LVEF < 40% or HRv < 20 units gave a sensitivity of 75%, positive
      predictive accuracy of 30%, and a risk ratio of 30 in young patients (p < 0.001),
      but the relation between this combination and sudden death in older patients was
      not statistically significant. CONCLUSION: In postinfarction patients aged < 60
      sudden death was a more predominant mode of death and was more reliably predicted
      from a depressed HRv index, an LVEF < 40%, and VE10 than in older postinfarction
      patients. These findings may have important implications for post-infarction risk
      stratification and management.

PMID- 1382507
TI  - Multiple microsurgical toe-to-hand transfer in the reconstruction of the severely
      mutilated hand. A series of fifty-nine cases.
AB  - The severely mutilated hand is defined as the hand which has lost opposable digit
      function either through: a) The amputation of all four fingers proximal to the
      PIP joint or b) The loss of the thumb proximal to the IP joint combined with the
      loss of at least three fingers proximal to the PIP joint. We have outlined
      guidelines for the restoration of useful function and appearance to such hands
      utilising a variety of microsurgical toe-to-hand transfers. Specific points
      regarding postoperative management have been made.

PMID- 1382506
TI  - Establishment and characterization of a new murine cell line (SR-4987) derived
      from marrow stromal cells.
AB  - A new murine cell line designated as SR-4987 was established by treating a long
      term bone marrow culture with the supernatant from Y-1 cells which actively
      produce viral C-particles (MuLV). The line showed a fibroblast-like morphology
      and its mesodermal origin was confirmed by immunocytochemical staining. Flow
      cytometric analysis of DNA index evidenced a tetraploid number of chromosomes
      whereas cell cycle analysis showed 34.8% of cells in S phase and 60.7% in G1. In
      vitro growth studies demonstrated a population doubling time of 14.7 h, a good
      plating efficiency (52.3%) and a very poor agar clonogenic capacity (0.6%). SR
      4987 was tumorigenic only in syngeneic mice in which sarcomas were induced. The
      line produced M-CSF in the culture supernatant whereas G-CSF, IL-3 and GM-CSF
      were not detected. Studies are in progress to assess the production of other
      cytokines and to verify if same autocrine growth factor is involved in the
      control of SR-4987 proliferation. Our line provides a further model of stromal
      cells for studying the interaction between hemopoietic progenitors and their
      microenvironment, as well as to study factors produced by stromal cells acting as
      modulators of proliferation and differentiation of related cell populations.

PMID- 1382508
TI  - The results of conservative management of trigger finger. A series of 169
      patients.
AB  - The authors present the preliminary results of a series of 230 trigger fingers in
      169 patients managed conservatively by injection of 1 ml of hydrocortisone into
      the flexor sheath as described by Curtis. 'Good' results were obtained after a
      single infiltration in 73% cases, after two infiltrations in 81.6% cases and in
      83% cases after three infiltrations. Factors have been studied in order to
      identify variables with prognostic significance. The outcome was not influenced
      by the severity of symptoms, by the association with other disease, by sex or by
      the site of pathology. Outcome was affected by the duration of symptoms. Duration
      exceeding one year indicates surgical release as does failure of conservative
      treatment.

PMID- 1382509
TI  - Staged flexor tendon reconstruction in children.
AB  - The medical records of 12 children, aged 1 to 15 (mean 8.4 years) who had a total
      of 14 staged flexor tendon reconstructions for zone 2 flexor tendon injuries
      between the years of 1974 and 1989 were reviewed. One patient with one treated
      finger was lost to follow-up one month after Stage II surgery. The rest were
      followed either to failure or for a minimum of six months after Stage II surgery
      (range 6 to 108 months; mean 45 months). Results were graded by the percentage of
      total passive motion after Stage I converted to active motion after Stage II, and
      the final total active motion (TAM). Overall, there were seven poor, one fair,
      two good, and three excellent results. Mean final TAM was 140 degrees (range 90
      210 degrees). Results were better in those children whose rehabilitation was
      supervised by a trained hand therapist (three excellent, one good, and one poor
      result). Complications included four infections after Stage I, and one infection
      and one rupture after Stage II. After treatment, these complications resulted in
      four poor results. Staged flexor tendon reconstruction in children in this series
      had a higher risk of complications and failure than the same procedure in adults
      reported in a previous series from this institution. Results in children may be
      improved by close attention to postoperative care and by patient selection based
      on ability to cooperate with the postoperative program.

PMID- 1382511
TI  - Severe electric injuries of the hand and forearm.
AB  - Electrical injuries of the upper limb produce major destruction of tissue mainly
      affecting the forearm, since the hand is usually the site of entry of current.
      Limb salvage, if it is to be successful, requires the rapid institution of a
      number of surgical procedures. Vein grafting to restore blood supply is
      frequently required and just as frequently requires skin flap cover following
      adequate debridement. The most commonly used flap is the groin flap. Despite the
      progression of necrosis beneath the flap for a period of up to three weeks,
      healing is usually successful and it is usually possible to avoid amputation.
      Several surgical procedures are required as a rule. The initial surgery is
      followed, in order, by nerve graft, tendon transfer and skin transfer following
      the use of tissue expanders. Results long term, with regard to function and
      appearance, were judged good.

PMID- 1382510
TI  - Flexor tendon suture in zone 1 and distal zone 2 by the Mantero technique.
AB  - A series of 161 digits with flexor tendon division in zones 1 and 2 have been
      reviewed after management by the method described by Mantero. The concept of
      "urgence differee" (delayed primary suture) is still valid. In zone 2, we
      distinguish between division of tendons, where only profundus is divided (zone
      2.1) and, where both profundus and superficialis are divided (zone 2.2). Results
      from zone 2.1 are comparable to results from zone 1. Overall, our results are of
      the order of those achieved by management according to Kleinert, but we would
      maintain that the Mantero technique is easier to perform and more confortable for
      the patient.

PMID- 1382512
TI  - A new flap based on the distal branches of the radial artery.
AB  - A flap based on the distal branches of the radial artery is raised on the dorso
      lateral aspect of the distal third of the forearm. Thirty fresh cadaver
      dissections have established the anatomical rationale of the flap. The potential
      territory is supplied by a subaponeurotic plexus of vessels fed by lateral
      branches of the radial artery in the distal third of the forearm. This new
      knowledge of the anatomy has been applied to the performance of this flap in
      seven clinical cases. Various methods of application to hand and wrist
      reconstruction are described along with a discussion of the various advantages
      and disadvantages.

PMID- 1382513
TI  - MRI of hand and wrist with a dedicated low field mini imager: preliminary report.
AB  - In this paper we describe the development and the early results of an MRI system
      designed specifically for imaging of the hand and wrist. The imager takes up
      little space, uses a small 0.1 Tesla water-cooled electro-magnet with a vertical
      magnetic field and a 15 cm air gap. The system is based on a PC micro-computer
      and an integrated image processing board. There is no need for a Faraday cage.
      The image resolution is less than 1 mm using a 128 x 128 matrix format for a
      typical slice thickness of 3 mm. It is possible to achieve a 0.2 mm per pixel
      spatial resolution when imaging the fingers.

PMID- 1382514
TI  - Dorsal dislocation of the triquetrum: a case report.
AB  - A case of dorsal dislocation of the triquetrum associated with a dorsal
      dislocation of the distal radioulnar joint is reported. Open reduction and
      transfixation with Kirschner wires was performed. Eighteen months afterwards, the
      patient had marked volar intercalary segment instability deformity of the wrist
      joint assessed radiographically, with approximately half loss of range of motion
      of the wrist and grip strength.

PMID- 1382515
TI  - The right hand of Robert Schumann.

PMID- 1382516
TI  - Aluminum accumulation in serum, liver and spleen of Fe-depleted and Fe-adequate
      rats.
AB  - The study described here was planned to test the hypothesis that Al absorption
      and accumulation in the body are inversely related to Fe status. Aluminum3+ and
      Fe3+ have similar ionic radii and charge densities, pH-solubility relationships,
      and affinities for ligands, such as citrate and transferrin. Male weanling
      Sprague-Dawley rats were pair fed an Fe-deficient or Fe-adequate (control) diet
      for 2 wk. Each diet group was then randomly assigned to receive for four more
      weeks the Fe-deficient or adequate diet with: 1. 2% AlCl3; 2. AlCl3 + 3.5% Na
      citrate; or 3. No Al or citrate. Iron depletion, confirmed by measurements of
      hemoglobin, hematocrit, serum Fe, and Fe binding capacity, increased
      concentrations of serum, liver, and spleen Al in all groups fed AlCl3. However,
      the increase owing to Fe deficiency was significant only when Al was fed with
      citrate. The data suggest that Fe deficiency enhances both Al absorption and
      accumulation in liver and spleen.

PMID- 1382517
TI  - Comparison of molecular properties of rat plasma and erythrocyte selenium
      dependent glutathione peroxidase.
AB  - The molecular structure of plasma and erythrocyte selenium-dependent glutathione
      peroxidase (GSH-Px) was studied in rats drinking water containing [75Se]selenious
      acid, 1.3 mg Se/L. Substantial differences were found using three-step
      fractionation, including gel filtration of crude plasma and erythrocyte lysate,
      gel filtration of 75Se-GSH-Px treated by mercaptoethanol, and SDS
      electrophoresis. Native plasma 75Se-GSH-Px, which exhibited a molecular weight
      (M(r)) of approx. 700,000, could be destroyed by mercaptoethanol action,
      resulting in disintegration of enzyme into several different 75Se-protein
      fragments and release of part of low-mol-wt 75Se. Native erythrocyte 75Se-GSH-Px
      M(r) value was found to be 113,000; two 75Se-protein fragments arose after
      mercaptoethanol treatment without 75Se release from the enzyme. The 75Se-subunits
      of 22,500 and 21,900 were isolated from plasma and erythrocyte 75Se-GSH-Px,
      respectively. Another minor 75Se-GSH-Px was identified in erythrocyte lysate
      (M(r) 214,000, subunit 22,100), which was considered to be a dimer of the above
      mentioned erythrocyte enzyme. It can be assumed, based on these data, that native
      plasma GSH-Px, in contrast to erythrocyte enzyme, represents a high-molecular wt
      complex composed of several tetramers linked with S-S bonds. A certain part of
      selenium present in this complex is probably not selenocysteine and may be
      released with the mercaptoethanol treatment.

PMID- 1382518
TI  - Changes in free radicals, trace elements, and neurophysiological function in rats
      with liver damage induced by D-galactosamine.
AB  - The changes in trace elements, free radicals, and neurophysiological function
      were investigated in rats with liver damage induced by D-galactosamine (GalN).
      The elevated results showed that all the parameters related to free radical
      metabolism changed after administration of GalN. Relative free radical
      concentration, malonaldehyde (MDA), and oxidized glutathione (GSSG) elevated, but
      reduced glutathione (GSH) decreased. Concurrently, zinc, copper, manganese, and
      selenium contents in liver were significantly reduced, whereas iron was elevated.
      In rats with hepatic encephalopathy (HE) owing to fulminant hepatic failure (FHF)
      induced by a high dosage of GalN, the latencies of VEPs were delayed. Moreover,
      there is a correlation between Zn content of brain and the latencies of VEPs. The
      results of this study suggested that lipid peroxidation by free radicals might be
      responsible for GalN-induced liver damage in which trace elements were involved,
      and that change in brain Zn might play a role in the neural inhibition of HE
      owing to FHF.

PMID- 1382520
TI  - Inhibitory effects of some natural products on metal-induced lipid oxidation in
      cooked fish.
AB  - Divalent metal ions (Fe2+, Cu2+, Zn2+, Ni2+, and Mn2+) induced lipid oxidation in
      cooked, but not in raw fish. The extent of lipid oxidation, measured by the
      production of thiobarbituric acid reactive substances (TBRS), was increased with
      higher concentrations of iron, zinc, and nickel, but was decreased with
      increasing concentrations of copper and manganese. The natural products: ellagic
      acid, tannic acid, myricetin, and quercetin, inhibited lipid oxidation in cooked
      fish. The enhanced lipid oxidation caused by cupric ions (10(3) pmol/100 g fish)
      was also inhibited by the natural products. The degree of inhibition in copper
      treated fish, however, was less than that in fish that had no added copper. The
      inhibition was concentration dependent. The antioxidative potency of the various
      natural products was independent of the type of metal ion-induced lipid
      oxidation. Ellagic acid was the most potent antioxidant (75.7-83.9%), followed by
      tannic acid (60.4-77.3%), myricetin (52.9-70.4%), and quercetin (32.6-44.2%).

PMID- 1382519
TI  - Protective effect of zinc on liver injury induced by D-galactosamine in rats.
AB  - The protective effects of zinc on liver injury induced by D-galactosamine (GalN)
      were investigated in rats in vivo and in vitro. Zinc supplementation (50 mg/kg/d)
      for 5 d of rats treated with GalN (1.5 g/kg, ip) could reduce their mortality
      rate, restore liver pathomorphological changes, maintain zinc content, inhibit
      the lipid peroxidation, hasten the protein synthesis, and improve liver function.
      In vitro, zinc supplement could abate the death of GalN-intoxicated hepatocytes,
      decrease malonaldehyde (MDA) content, and maintain reduced glutathione (GSH). It
      is concluded that zinc has protective effects on GalN-induced liver damage. Its
      effects may be owing to inhibition of lipid peroxidation and hastening of protein
      syntheses.

PMID- 1382521
TI  - ATP-dependent strontium uptake by basolateral membrane vesicles from rat renal
      cortex in the absence or presence of calcium.
AB  - ATP-dependent Sr2+ transport was examined in vitro using basolateral membrane
      (BLM) vesicles isolated from rat renal cortex to clarify the discrimination
      mechanisms between strontium (Sr) and calcium (Ca) in renal tubules during
      reabsorption. ATP-dependent Sr2+ uptake and Ca2+ uptake were observed in renal
      BLM vesicles and were inhibited by vanadate. Hill plots indicate similar kinetic
      behavior for Ca2+ and Sr2+ uptake. The apparent Km and Vmax of ATP-dependent Sr2+
      uptake were both higher than those for Ca2+ uptake. ATP-dependent Sr2+ uptake by
      BLM vesicles diminished in the presence of 0.1 microM Ca2+ and was more markedly
      inhibited by 1 microM Ca2+. Hill plots of Sr2+ uptake data with and without 0.1
      microM Ca2+ showed that the cooperative behavior of Sr2+ uptake was not changed
      by Ca2+. In the presence of 0.1 microM Ca2+, the affinity of the transport system
      for Sr2+ and the velocity of Sr2+ uptake in the BLM were both decreased. However,
      the rate of Ca2+ uptake was not diminished by Sr2+ concentrations of less than
      1.6 microM. These results suggest that Ca2+ is preferentially transported in the
      renal cortex BLM when Ca2+ and Sr2+ are present at the same time.

PMID- 1382522
TI  - Effects of maternal marginal zinc deficiency on myelin protein profiles in the
      suckling rat and infant rhesus monkey.
AB  - In the current study, the effects of marginal Zn deficiency on myelin protein
      profiles in neonatal rats and rhesus monkeys were investigated. Following mating,
      rats were fed a Zn-adequate diet, ad libitum (50 micrograms Zn/g; 50 Zn AL), or a
      marginal Zn diet (10 micrograms Zn/g) from day 0 (10 Zn d0) or day 14 (10 Zn d14)
      of gestation to day 20 postnatal. An additional group of dams was restricted-fed
      the control diet to the food intake of the 10 Zn d0 group (50 Zn RF). Day 20 pup
      plasma and liver Zn concentrations in the 10 Zn groups were lower than in the 50
      Zn groups. In a parallel experiment, rhesus monkeys were fed a Zn-adequate ad
      libitum diet (100 micrograms Zn/g) or a marginal Zn diet (4 micrograms Zn/g diet;
      MZD) throughout gestation and lactation. Day 30 monkey infant plasma and liver Zn
      levels were similar in the MZD and control groups. Rat brain and monkey brain
      cortex weights were similar among the dietary groups. The amount of myelin
      recovered (mg protein/g brain) from day 20 rat pups from the 10 Zn groups was
      lower than that recovered from the 50 Zn rat pups. Myelin recovery from the MZD
      and control monkey infants was similar. When myelin protein profiles were
      characterized, it was found that the percentages of high-molecular-weight (HMW)
      proteins and Wolfgram protein were higher, whereas the percentages of small and
      large basic proteins were lower in myelin from the 10 Zn d0 and 50 Zn RF pups
      compared to the distribution in the 50 Zn AL rat pups. Results for the 10 Zn d0
      and 10 Zn d14 pups were similar for all of the parameters studied. The percentage
      of HMW proteins was higher and that of basic protein lower in myelin from MZD
      monkey infants compared to the percentage of these proteins in myelin from
      controls. Although the interpretation of the rat data is complicated because of
      the anorexia associated with Zn deficiency, the observed changes in monkey myelin
      protein profiles provide strong evidence that maternal Zn deficiency affects
      myelination in the offspring.

PMID- 1382523
TI  - Absorption, endogenous excretion, and balance of zinc in growing rats on diets
      with various sugars replacing starch.
AB  - The effect of partially replacing starch for various sugars on the apparent and
      true absorption, endogenous excretion, and balance of zinc was investigated in a
      study with growing rats. Six groups of five or six animals with an initial live
      weight of 39.4 +/- 2.7 g were fed diets that had the same Zn content (22 mg/kg),
      but differed in the sugar content: 1. Starch only (56%); 2. Glucose (15%); 3.
      Fructose (15%); 4. Sucrose (30%); 5. Galactose (15%); and 6. Lactose (30%). At
      the start of a 15-d fecal and urinary collection period, each animal was given an
      intramuscular injection of 380 kBq 65Zn for estimating endogenous Zn excretion by
      isotope dilution. The ratio of the specific activity of fecal Zn (after 12 d) to
      that of urinary Zn (after 9 d) was applied to reflect the ratio of endogenous to
      total fecal Zn collected from day 10 to 15. This ratio averaged 0.59, without
      significant differences among treatments. For this period, apparent and true
      absorption averaged 87.1 and 94.7% of Zn intake, respectively, and did not
      significantly differ among diets. Urinary excretion of 65Zn and of stable zinc by
      the galactose-fed rats was markedly higher than that by the other animals. Their
      Zn balance was, per unit weight gain, comparable with that of the other groups
      (30.7 vs 28.2 to 30.2 micrograms/g).

PMID- 1382524
TI  - Aluminum transfer through milk in female rats intoxicated by aluminum chloride.
AB  - Female rats received an ip injection of aluminum chloride (10 mg Al/kg/d) during
      the first 12 d after parturition; this treatment led to a reduction in food
      intake associated with a reduction in body wt. Pups of the intoxicated dams
      showed a growth retardation after postnatal day 7. One day after treatment, the
      female rats intoxicated with aluminum had a considerably higher level of aluminum
      in milk than controls. The aluminum levels of plasma, liver, spleen, and kidneys
      were also significantly higher in treated female rats than controls. On the
      contrary, in the same tissues of pups from treated or not treated dams, no
      differences in aluminum levels were observed. No effect of aluminum treatment was
      detected on plasma silicon levels in dams and pups.

PMID- 1382525
TI  - Elements in hair and nails of urban residents of New Delhi. CHD, hypertensive,
      and diabetic cases.
AB  - The concentrations of Cd, Cr, Cu, Mn, Ni, Pb, and Zn were estimated in hair and
      nails of urban residents of New Delhi. Particularly, hair levels of Cu and Mn in
      hypertensive males, Cr and Zn in hypertensive females, and Zn in CHD and diabetic
      females, and nail levels of Zn in CHD and hypertensive females were significantly
      lower than controls. Thus, it is observed that there exists some positive
      correlation between element levels in hair and nails and CHD, hypertension, and
      diabetes of these subjects.

PMID- 1382527
TI  - Immunological monitoring and clinical trials of biological response modifiers.

PMID- 1382526
TI  - Elements in hair and nails of residents from a village adjacent to New Delhi.
      Influence of place of occupation and smoking habits.
AB  - Samples of hair and nails collected from the residents of Wazirpur, a village
      adjacent to New Delhi, were analyzed for Cd, Cr, Cu, Mn, Ni, Pb, and Zn, and
      correlated with the residents' rural and urban places of occupations. It was
      observed that Pb and Cd hair levels of males working in rural areas were lower
      than in male businessmen and officers working in an urban area of New Delhi,
      thereby showing the different levels of elements exposure of the rural subjects.
      Such differences in the hair levels of elements were not observed among female
      subjects. The tobacco smoking habits of male and female rural subjects using
      hookah were associated with increased Cd levels in hair and nails.

PMID- 1382528
TI  - Colony-stimulating factors in cancer therapy.

PMID- 1382529
TI  - Bleomycins.

PMID- 1382530
TI  - AIDS surveillance in the Americas.

PMID- 1382531
TI  - [Hyperamylasemia or macroamylasemia? A clinical case].
AB  - The authors report a case of macroamylasaemia and discuss diagnostic implications
      especially in surgical emergencies. In fact, laboratory findings of
      hyperamylasaemia may lead to erroneus diagnosis or even to useless surgical
      operations.

PMID- 1382532
TI  - Phylogenetically conserved amino acids of MBP and P0 from amphibian myelin.
AB  - Myelin basic protein (MBP) and P0 glycoprotein are major structural proteins of
      myelin. In adult frog, MBP is found in both the central and peripheral nervous
      systems (CNS and PNS), while P0 is found exclusively in the PNS. To assess the
      phylogenetic conservation of these proteins, MBP and P0 were isolated from adult
      bull-frog. A cyanogen bromide cleavage peptide of MBP (8-26), and the amino
      terminal region (1-20) and an endoproteinase Lys-C peptide (67-79) of P0 were
      sequenced and compared to those of other vertebrate species. Residues that were
      conserved among other vertebrate species were found also to be conserved in frog:
      MBP--Ala18, Ser19, Thr20, Asp22; P0--Ile1, Val3, Thr5, Val13, Gly14, Ser15,
      Val17, Leu19, Trp72, Val73, Gly74, Lys79. These residues are located within or
      adjacent to regions that have been postulated to form beta strands and to be
      essential to the folding and function of these proteins.

PMID- 1382533
TI  - Isolation and characterization by cell density adjustment of a PC12
      pheochromocytoma variant with altered Ca2+ homeostasis.
AB  - Rat PC12 pheochromocytoma cells loaded with the fluorescent Ca2+ dye fluo-3 or
      indo-1 and scanned fluorimetrically on a cell sorter apparatus showed a rapid
      cell density-dependent increase in free cytosolic calcium concentration [Ca2+]i
      when maintained in suspension cultures. Cell adhesion, measured under a defined
      set of conditions, was low when cells were seeded at 1.5 x 10(4) cells/ml but
      reached maximal levels after addition of A23187 calcium ionophore. A six to
      sevenfold increase in cell density mimicked the effect of the ionophore.
      Densities above 2 x 10(6) cells/ml caused a decrease in cell adhesion, which was
      further reduced by the addition of A23187. BAPTA, AM (1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) and nifedipine (10 microM each),
      partially inhibited cell attachment (34% and 44% reduction), but at 0.25 microM
      and 1 microM, respectively, they enhanced attachment (46% and 67% increase). The
      data suggest that a certain permissive level of [Ca2+]i, attained by either
      increasing cell density or by the presence of a calcium ionophore, is sufficient
      for maximal cell adhesion. Above the permissive level, manipulation of [Ca2+]i
      either by altering cell density or by the addition of calcium blocking agents in
      high concentrations results in a significant reduction in cell adhesion. Based on
      these observations, we were able to isolate a biochemically and morphologically
      distinct cell population. The variant, designated PC12ds (density selected),
      differed substantially from the original cells. Most notable was a relatively
      lower content of free [Ca2+]i in the PC12ds cells, as independently assayed by
      using fluo-3 and indo-1 dyes. In addition, the variant cells exhibited a
      significantly diminished rate of 45Ca2+ uptake, most likely due to less efficient
      L-type voltage-dependent calcium (VDC) channels. Addition of several calcium
      channels agonists and antagonists suggested that PC12ds cells contained
      relatively more N-type VDC channels, possibly indicating a shift to a neuronal
      phenotype.

PMID- 1382534
TI  - Cholera in 1991.

PMID- 1382535
TI  - Compression hosiery in a surgical unit.
AB  - A small pilot study was set up to indicate the appropriateness of the assessment
      of patients for anti-embolus prophylaxis in a surgical unit. The results
      suggested some flaws in current practice, particularly in relation to assessment
      of risk factors and patient information procedures. Discussions with ward staff
      on the results have initiated changes in nursing interventions which will be
      evaluated on an on-going basis.

PMID- 1382536
TI  - Marinobacter hydrocarbonoclasticus gen. nov., sp. nov., a new, extremely
      halotolerant, hydrocarbon-degrading marine bacterium.
AB  - On the basis of phenotypical characteristics and analysis of 16S rRNA sequence, a
      new species belonging to a new genus is described, and the name Marinobacter
      hydrocarbonoclasticus is proposed. This organism, isolated from Mediterranean
      seawater near a petroleum refinery, is a gram-negative, aerobic, rod-shaped
      bacterium. It grows at NaCl concentrations of 0.08 to 3.5 M and uses various
      hydrocarbons as the sole source of carbon and energy. Its DNA has a guanine-plus
      cytosine content of 52.7 mol%. The 16S rRNA analysis shows a clear affiliation
      between M. hydrocarbonoclasticus and the gamma group of the phylum
      Proteobacteria. A close phylogenetic relationship appears among the species
      Marinomonas vaga, Oceanospirillum linum, Halomonas elongata, and Pseudomonas
      aeruginosa. Because of the impossibility of finding a single most closely related
      species, we suggest that this bacterium be assigned to a new genus, at least
      temporarily. The possibility of a revision of this status when new data appear
      is, however, not excluded. The type strain is M. hydrocarbonoclasticus SP.17 (=
      ATCC 49840).

PMID- 1382537
TI  - Widespread folliculitis induced by human granulocyte-colony-stimulating factor
      therapy.

PMID- 1382538
TI  - Dermatofibrosarcoma protuberans is a unique fibrohistiocytic tumour expressing
      CD34.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a slow growing, locally invasive tumour
      whose differentiation from other fibrohistiocytic tumours sometimes poses serious
      diagnostic problems. We investigated CD34 expression immunohistologically in
      various fibrohistiocytic tumours including dermatofibroma, DFSP, malignant
      fibrous histiocytoma (MFH), infantile myofibromatosis, fibrosarcoma, hypertrophic
      scar and keloid. Among these, DFSP was unique in that tumour cells themselves
      expressed CD34, whereas in other tumours. CD34 expression was observed only on
      vascular endothelial cells amongst the tumour cells. Until now, there have been
      no reports of useful immunohistological markers for DFSP. CD34 expression by the
      tumour cells can be an extremely useful marker in establishing a definitive
      diagnosis of DFSP.

PMID- 1382539
TI  - Further studies on the actions of endothelin-1 on blood flow in human skin.
AB  - When injected into human skin, endothelin-1 produces intense vasoconstriction
      localized to the site of the injection, but this area of vasoconstriction is
      surrounded by vasodilatation which spreads several centimetres from the injection
      site. The vasodilatation induced by intradermal injection of endothelin-1 (63
      pmol) into human skin is prevented by local anaesthetic. Pretreatment of human
      skin with capsaicin also inhibits this response. Pretreatment of subjects with
      the selective histamine H1-receptor antagonist cetirizine, 10 mg orally 4 h
      before intradermal injections, inhibited vasodilatation caused by the intradermal
      injection of histamine (750 pmol), endothelin-1 (63 pmol), and carbachol (750
      pmol). Endothelin-1 (0.3-10 microM) and carbachol (1-30 microM) failed to induce
      histamine release from rat peritoneal mast cells. We conclude that the
      vasodilatation caused by intradermal injection of endothelin-1 into human skin is
      neurogenic and is probably mediated by neuropeptide-containing primary afferent
      neurones. Because neither carbachol nor endothelin-1 cause histamine release from
      mast cells, our data suggest that histamine release from mast cells at the
      effector end of the axon reflex is responsible for the carbachol- and endothelin
      induced vasodilatation in human skin.

PMID- 1382540
TI  - Modern treatment of warts: cure rates at 3 and 6 months.
AB  - Four-hundred consecutive referrals with viral warts of the hands and/or feet were
      investigated to determine the cure rate from a combination of cryotherapy,
      keratolytic wart paint and paring. For treatment failures after 3 months, the
      value of continuing cryotherapy and of additional treatment with the
      immunomodulator inosine pranobex were assessed. Subjects were treated for 3
      months with wart paint and cryotherapy and were randomized to receive, or not,
      paring in addition. Those who did not respond by 3 months were randomized to
      receive, or not, 3 months further cryotherapy, and to receive inosine pranobex 60
      mg/kg/day for 1 week each month, or matching placebo. Fifty-two per cent of
      subjects were cured by 3 months. The chance of cure was inversely related both to
      the length of history and to the diameter of the largest wart. Paring improved
      the cure rate for plantar warts but not for hand warts. During the second 3
      months the cure rate fell to 41%. Neither cryotherapy nor inosine pranobex
      significantly improved this response.

PMID- 1382541
TI  - Effects of platelet activating factor (PAF) and other vasoconstrictors on a model
      of angiogenesis in the mouse.
AB  - The combination of sponge implant and 133Xe washout technique described in this
      paper provides a model to study neovascularization in mice which can be observed
      over several days in the same animal. The local blood flow within the ingrowing
      granulation tissue has been determined by measuring the washout rate of 133Xe
      injected into the implants. Tissue infiltration of the sponges was assessed by
      histological examination and by measurement of sponge wet weight, protein and
      glycosaminoglycans (GAG) content. The newly formed blood vessels, despite having
      abnormal configuration, responded to platelet activating factor (PAF) and to
      endothelin-1 (ET-1) similarly to the normal mature vessels in adjacent skin.
      However, the sponge blood vessels were more sensitive to angiotensin II than the
      skin blood vessels. Using this model we have also demonstrated an angiogenic
      activity of PAF substantiated by increased blood flow and biochemical variables
      in the implanted sponges.

PMID- 1382542
TI  - The in vitro effect of high-dose recombinant human erythropoietin on granulocyte
      macrophage colony production in premature infants using a defined serum deprived
      cell culture system.
AB  - Recent reports of neutropenia associated with the use of recombinant human
      erythropoietin (r-HuEpo) in preterm infants with the anaemia of prematurity have
      raised concern over the clinical use of this hormone. The present studies were
      undertaken to determine whether high-dose r-HuEpo has an effect on granulocyte
      production in vitro. The studies used a serum deprived, optimized semi-solid cell
      culture system to investigate the effect of lineage specific and non-specific
      granulocyte and erythroid colony stimulating factors on circulating peripheral
      blood granulocyte-macrophage colony forming units (CFU-GM), erythroid burst
      forming units (BFU-E) and multilineage colonies (CFU-Mix) from nine premature
      infants and seven healthy adults. CFU-GM were grown in the presence of
      interleukin 3 (IL3) 8 ng/ml, granulocyte-macrophage colony stimulating factor (GM
      CSF) 20 ng/ml and granulocyte colony stimulating factor (G-CSF) 15 ng/ml alone
      and combinations of G-CSF with GM-CSF or IL3. The number, size and
      differentiation of CFU-GM colonies were then analysed in the presence and absence
      of high dose r-HuEpo (4 U/ml). High-dose r-HuEpo did not exert any significant
      modulatory effects on the number of CFU-GM colonies produced in the presence of
      IL3, GM-CSF and G-CSF alone or in combination. The number of cells within each
      CFU-GM colony did not change significantly, nor was there a significant change in
      the degree of differentiation. The combined number of BFU-E, CFU-GM and CFU-Mix
      colonies increased with r-HuEpo in both adults (1.8 x) and preterm infants (1.4
      x), almost exclusively due to an increase in BFU-E derived colonies. Thus, no
      evidence was found for an r-HuEpo mediated redirection of multipotential
      haemopoietic stem cells into committed erythroid precursors at the expense of
      myeloid precursors.

PMID- 1382543
TI  - Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human
      plasma cells.
AB  - Normal and malignant plasma cells were investigated for the expression of seven
      cellular adhesion molecules by immunofluorescence microscopy. The antigens
      investigated were CD2 and its ligand, LFA-3 (CD58). LFA-1 alpha (CD11a) and LFA-1
      beta (CD18) and their ligand ICAM-1 (CD54), H-CAM (lymphocyte homing receptor;
      CD44) and N-CAM (CD56). Marrow from 18 patients with myeloma, two with plasma
      cell leukaemia (PCL), four with monoclonal gammopathy of uncertain significance
      (MGUS) and 10 normal allogeneic bone marrow donors was studied. All plasma cells
      from normals and multiple myeloma patients were negative for CD2, CD11a and CD18.
      All normal and myeloma marrow plasma cells were positive for ICAM-1. 16/18
      myeloma cases tested, and all other samples (normal, MGUS and PCL), contained
      plasma cells positive for H-CAM. Only one normal, but 12/16 myelomas tested were
      positive for N-CAM (P less than 0.02). One of four MGUS cases was moderately
      positive and one other weakly positive for N-CAM. Both PCLs were N-CAM negative.
      12/18 myelomas were positive for LFA-3, but only two normals (P less than 0.05).
      All MGUS cases were negative for LFA-3, as was one PCL, the other being weakly
      positive. Three cases were negative for both adhesion molecules, three cases
      expressed only N-CAM or LFA-3 and 10 cases expressed both. LFA-3 and N-CAM are
      expressed significantly in myeloma rather than normal plasma cells. Cases of MGUS
      may express N-CAM but not, in this small series, LFA-3. Plasma cells in the
      peripheral blood (PCL) and plasma cell lines express little or no LFA-3 or N-CAM.

PMID- 1382544
TI  - Further characterization of the NB 1 antigen as a variably expressed 56-62 kD GPI
      linked glycoprotein of plasma membranes and specific granules of neutrophils.
AB  - The human neutrophil-specific alloantigen NB1 was identified as a glycosyl
      phosphatidylinositol (GPI)-anchored N-glycosylated protein of M(r) 56-62 kD under
      reducing conditions. Under non-reducing conditions its M(r) was 49-55 kD. This
      glycoprotein antigen was found to be expressed by only a subpopulation of normal
      donor neutrophils, and could not be detected on other blood cells. The allotypic
      epitope recognized by human anti-NB1 IgG was also recognized by the mouse
      monoclonal antibody 1B5. The percentage of neutrophils stained by these
      antibodies varied greatly among healthy donors (range 0-100%). When 16 donors
      were repeatedly tested, the NB1-positive neutrophil fraction appeared to remain
      remarkably constant over time in most donors, but significant fluctuations were
      seen in some. NB1 antigen was found to be expressed not only on the plasma
      membrane, but also intracellularly on the membranes of small vesicles and
      specific granules. The neutrophils which expressed NB1 antigen on the plasma
      membrane were the same as those with intracellular expression of this antigen.
      Crosslinking of NB1 antigen on the plasma membrane with monoclonal antibody 1B5
      and goat-anti-mouse Ig resulted in internalization of the complex, while in-vitro
      stimulation of neutrophils caused an increase of the intensity of plasma membrane
      staining with anti-NB1, but only of those cells that were positive already prior
      to stimulation. The NB1 glycoprotein thus appears to identify a distinct subset
      of neutrophils, the size of which greatly varies among healthy donors. The
      function of the NB1 glycoprotein remains unclear, but its behaviour upon
      crosslinking and chemotactic peptide stimulation suggests a possible role as
      receptor molecule.

PMID- 1382545
TI  - Bone marrow involvement in non-Hodgkin's lymphoma: increased diagnostic
      sensitivity by combination of immunocytology, cytomorphology and trephine
      histology.
AB  - Diagnostic results from cytomorphology and immunocytology of aspirated bone
      marrow (BM) were compared with the findings from standard trephine histology of
      100 adult patients with non-leukaemic non-Hodgkin's lymphomas (NHL) in a
      retrospective study. Immunocytological investigations were performed by the
      immunoenzymatic APAAP-technique on BM smears monoclonal antibodies against CD19,
      Cd3, CD10 or TdT antigens and determination of positive cells in relation to
      total BM leucocytes. Corresponding results were obtained for trephine histology
      and for the combination of cytomorphology and immunocytology in 93/100 cases.
      Four cases with BM involvement by trephine histology were missed by the
      combination of immunocytology and cytomorphology. In turn, three cases negative
      by trephine histology, were found to be positive by the combination of
      immunocytology and cytomorphology. Immunocytochemistry considerably increased the
      number of true positive detected BM-infiltrations by cytomorphology in low grade
      B-cell lymphoma from 58% to 97%. For the diagnosis of BM involvement in high
      grade NHL cytomorphology of the aspirate was of equal sensitivity to the biopsy
      and was always confirmed by immunocytology. The high diagnostic sensitivity of
      immunocytology was mainly due to high B-cell counts in BM involved by B-cell
      lymphoma (means = 38%, s = 23) in contrast to low B-cell counts in BM not
      involved by NHL (means = 4.5%, s = 3.8). We conclude from our data that
      immunocytology in addition to standard cytomorphology improves diagnostic
      sensitivity in the detection of BM involvement by NHL.

PMID- 1382547
TI  - Identification of CD71 (transferrin receptor) expressing erythrocytes by
      multiparameter-flow-cytometry (MP-FCM): correlation to the quantitation of
      reticulocytes as determined by conventional microscopy and by MP-FCM using a RNA
      staining dye.
AB  - Reticulocytes express the CD71-defined antigen, the transferrin receptor. This
      report describes how by means of dual-colour immunofluorescence using MP-FCM
      (multiparameter-flow-cytometry) CD71+ erythrocytes can be detected regularly in
      blood of healthy adults. Percentages of these CD71+ erythrocytes were compared to
      the percentages of reticulocytes as determined by conventional microscopy using
      brilliant cressyl blue, and to the percentages of erythrocytes with high RNA
      content, as detected by MP-FCM using a RNA-staining dye (thiazole-orange). Only
      about two-thirds of the percentages determined by the two latter methods were
      detected by MP-FCM using the CD71 expression for definition of reticulocytes.
      Studying clinical samples, however, including both specimens with very low and
      very high numbers of reticulocytes, almost identical percentages were determined
      by all the three methods described. Studying reticulocytes in vitro, a rapid
      decline of the expression of the transferrin receptor was observed on
      reticulocytes. Due to the differential expression of the transferrin receptor on
      reticulocytes, different subsets of reticulocytes could be identified. The dual
      colour MP-FCM method described allows for the characterization and enumeration of
      immature erythrocytes, representing the major subset of reticulocytes as
      determined by conventional methods. Furthermore, it allows for subset dissection
      of reticulocytes.

PMID- 1382546
TI  - Acute myeloid leukaemia with an unusual phenotype: myeloperoxidase (+), CD13 (-),
      CD14 (-) and CD33 (-).
AB  - We herein describe an unusual case of acute myeloid leukaemia (AML) showing
      strong cytochemical reactivity for myeloperoxidase (MPO) but surprisingly no
      reactivity using flow cytometry for any of the lineage-specific cell surface
      markers, i.e. myelomonocytic antigens CD13, CD14 and CD33; or B-lymphoid antigens
      CD19, CD20 and immunoglobulins; or T-lymphoid antigens CD2, CD3 and CD5. The
      strong reactivity for MPO and the complete absence of reactivity for CD13 and
      CD14 was verified by an independent assay involving alkaline phosphatase-anti
      alkaline phosphatase (APAAP). Our case is of interest for at least two reasons:
      First, a poorly differentiated variant of AML (negative for MPO but positive for
      one or more of the myeloid-lineage CD antigens) has been designated FAB M0. In
      terms of the expression of phenotypic markers, our case may be considered as an
      'MPO (+), CD antigen (-) AML'. The CD antigens are known to be expressed very
      early during myeloid differentiation whereas MPO (in its functional form) is
      viewed as being expressed relatively late in the process. It is therefore
      intriguing from a biological standpoint why the supposedly early antigens (CD33
      and CD13) remain unexpressed; this may represent an example of 'asynchronous
      differentiation' in leukaemia. Second, from a practical standpoint, the use of
      immunophenotyping as a first-line diagnosis would fail to detect such cases. This
      case strengthens the notion that immunophenotyping by flow cytometry does not
      eliminate the necessity of performing peroxidase cytochemical staining.

PMID- 1382548
TI  - A variant of Glanzmann's thrombasthenia which fails to express a GPIIb-IIIa
      related epitope that is recognized by a specific monoclonal antibody (C17).
AB  - Binding of different antibodies to the GPIIb-IIIa complex in resting (AP2, EDU3,
      C17) or activated platelets (PAC1) was studied by flow cytometry in a patient
      with a platelet defect involving GPIIb-IIIa related functions. The patient has a
      mild history of bleeding. Aggregation induced by ADP and collagen were absent but
      normal response was obtained with ristocetin. Platelets from the patient do not
      bind fibrinogen. Perfusion studies with flowing blood showed that patient's
      platelets have a marked impairment in the process of spreading and aggregate
      formation on vascular subendothelium. Electrophoretic studies in SDS
      polyacrylamide gels demonstrated the presence of normal amounts and normal
      mobility of GPIIb-IIIa. Fibrinogen was present in the patient's platelets (68-74%
      of controls). The binding of AP2 and EDU3 to patient's resting platelets was
      normal as assessed by flow cytometry. In contrast, a decreased presence of the
      C17 antigen (10 fold lower than control platelets) was detected in resting
      platelets and a markedly reduced binding of PAC1 was found in thrombin activated
      platelets. These studies suggest that C17 recognizes an epitope of the GPIIb-IIIa
      in resting platelets that is implicated in the regulation of adhesive and
      cohesive properties of GPIIb-IIIa. Studies on this patient might be helpful for
      the understanding of GPIIb-IIIa functions.

PMID- 1382549
TI  - Lupus-like anticoagulant properties of murine monoclonal antibodies to beta 2
      glycoprotein I.
AB  - The lipid-binding inhibitor of coagulation, beta 2-glycoprotein I (beta 2GPI),
      has been shown to form the antigen to which some autoantibodies against anionic
      phospholipids (aPL) are directed. Six murine monoclonal antibodies (MAbs) of the
      IgG1 isotype were raised against human beta 2GPI and could be subdivided into
      three groups on the basis of mutual competition experiments. MAbs 9G1 and 8C3
      (group A) markedly inhibited the binding of immunoglobulins from aPL-positive
      sera to beta 2GPI-coated wells. Using a lipid-based solid-phase radioimmunoassay,
      the MAbs interacted with both anionic phospholipids and phosphatidylethanolamine,
      but not phosphatidylcholine, in a beta 2GPI-dependent manner. A cross-reaction
      between beta 2GPI from several (including bovine) species was seen with one of
      the MAbs (9G1). All six MAbs induced dose-dependent prolongation of the DAPTT,
      DRVVT, KCT and TTI clotting times of human plasma, whereas 9G1 was the sole
      antibody to be inhibitory with plasma from bovine origin. Synergistic inhibitory
      effects were observed with MAbs used in pairs provided that they did not compete
      with each other for beta 2GPI binding. The anticoagulant activity of the MAbs was
      fully neutralized by the addition of freeze-thawed platelets. The MAbs described
      here resemble lupus anticoagulants in several respects which makes them valuable
      to study the involvement of beta 2GPI in the autoimmune thrombotic
      pathophysiology.

PMID- 1382550
TI  - The rat liver cell nuclear imprint as a standard for DNA measurements.
AB  - Standards are used in DNA cytophotometry to determine the diploid reference
      value. Fixation and staining protocols have to be standardized because numerous
      sources of variation influence staining intensity of DNA. When Feulgen stained
      imprints of rat liver cell nuclei are used as an external DNA standard a
      significant difference of reference value of up to 60% between imprints, from the
      same liver and with all sources of variation minimized, is demonstrated.
      Different possible sources of intra-imprint variation were examined but its exact
      nature remains unknown. Due to this inter-imprint variation, the DNA-reference
      value from a single liver imprint is only an approximation with unknown error of
      the true diploid reference value. By drawing an aselective random sample of N
      diploid cells in M imprints the sampling distribution of TIOD (mean Total
      Integrated Optical Density) will have its expectation identical to the diploid
      reference value and is approached by TIOD (mean TIOD) with the confidence
      interval defined by the number, M, of imprints measured. The use of TIOD as an
      estimate of diploid reference value with known precision is proposed as a first
      approach for the definition of a standard for DNA measurements.

PMID- 1382551
TI  - Treatment of poor-risk germ-cell tumors with high-dose cisplatin and etoposide
      combined with bleomycin.
AB  - Seventy-two patients with far advanced ('high-risk') germ-cell tumors were
      treated with cisplatin 40 mg/m2 i.v. and etoposide 200 mg/m2 i.v. daily for 5
      days and bleomycin 15 mg/m2 i.v. once a week. At least 3 cycles of this treatment
      were given at three-week intervals to all patients. Seventy-five percent of the
      patients obtained CR and 67% are without evidence of disease after a median
      observation time of 47 months (range 5 to 80 months). Hematologic toxicity was
      severe and 10% of the patients died due to treatment-related toxicity.
      Neurotoxicity was a clinical problem in 58% of the patients. Glomerular
      filtration rate decreased significantly after 3 cycles (29% +/- 16%). No
      clinically significant pulmonary toxicity was observed. The specific role of high
      dose cisplatin in such intensive treatment has until now been the subject of only
      one randomized study in which no superiority of high-dose cisplatin was found.
      Significant improvement of therapeutic outcome over that of today's standard
      treatment conceivably necessitates an even greater increase in dose intensity of
      the active drugs--or inclusion of new drugs.

PMID- 1382552
TI  - The optimisation of carboplatin dose in carboplatin, etoposide and bleomycin
      combination chemotherapy for good prognosis metastatic nonseminomatous germ cell
      tumours of the testis.
AB  - An analysis of carboplatin dose response was performed in 121 patients with good
      prognosis metastatic nonseminomatous germ cell tumours (NSGCT) of the testis,
      referred to the Royal Marsden Hospital since 1984, who had been given combination
      carboplatin, etoposide and bleomycin (CEB) chemotherapy. With a median follow-up
      of 40 months (range: 7 to 85 months) nine patients (7%) have failed CEB.
      Carboplatin dose was analysed in all patients using body surface area (BSA) to
      derive a carboplatin dose per metre squared (mg/m2) and by calculation of a
      predicted serum concentration chi time (AUC: area under the curve) derived from
      the glomerular filtration rate (GFR), using the formula; Dose = AUC(GFR + 25). At
      a carboplatin dose of 400 mg/m2 or greater 2 out of 58 patients (3.4%) failed
      treatment while 7 out of 63 patients (11%) who received a dose less than this
      failed (p greater than 0.1). At an AUC of 5.0 mg.min/ml or greater, 2 out of 74
      patients (2.7%) failed while 7 out of 47 patients (14.9%) who had an AUC less
      than this failed (p less than 0.05). There was evidence for a dose/response
      relationship at relatively low doses and the failure rate rose to 26% for doses
      less than 4.5 mg.min/ml (p less than 0.001) or 15.6% for doses less than 350
      mg/m2 (p greater than 0.1). In view of the more precise determination of toxicity
      and efficacy it is recommended that carboplatin dose be based on the GFR.

PMID- 1382553
TI  - Cachexia and cancer: a clinician's view.
AB  - The cancer-related cachexia/anorexia syndrome is not well understood. It is
      related to several factors like metabolic changes, tumor types, and disease
      extent and is frequently accompanied by decreased performance status. An
      important aspect of anorexia is the psychosocial problem: the patient is unable
      to join the family for meals precisely when he or she most needs familial
      support. Several randomized studies have shown that megestrol acetate, possibly
      in a dose-dependent fashion, can improve appetite and lead to weight gain. This
      effect seems to be most prevalent in patients with breast cancer and also occurs
      in the absence of a tumor response. We have retrospectively analyzed 176 patients
      with cancer types other than breast cancer who received only palliative
      treatment. The patients were treated with megestrol acetate (160 mg tid) because
      they complained of anorexia. After 10 days of treatment, megestrol acetate was
      continued only in those patients whose appetite and/or general well-being
      improved. Fifty-seven patients (32%) experienced such an improvement and asked
      for continuation of therapy. Many basic questions are still unanswered;
      nonetheless, from a practical clinical view it seems worthwhile to offer
      anorectic patients a chance to improve, especially since side effects of
      megestrol acetate are absent or mild, and the distinction between responders and
      nonresponders can be made by 10 days of treatment.

PMID- 1382555
TI  - How should we palliate bladder cancer?

PMID- 1382554
TI  - HN-10200 causes endothelium-independent relaxations in isolated canine arteries.
AB  - HN-10200, a nonselective inhibitor of phosphodiesterase, has positive inotropic
      and vasodilator activity. The present study was designed to determine the role of
      endothelium in causing relaxation to HN-10200 in isolated canine femoral and
      basilar arteries. Rings with and without endothelium were suspended for isometric
      tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2, 6%
      CO2 (t = 37 degrees C; pH = 7.4). HN-10200 and another nonselective
      phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), caused similar
      concentration-dependent relaxations in femoral arteries with and without
      endothelium. In femoral arteries without endothelium, HN-10200 and IBMX
      significantly augmented relaxations to prostacyclin, but did not affect
      relaxations to a nitric oxide donor 3-morpholinosydnonimine (SIN-1) or
      endothelium-derived relaxing factor (EDRF) released by bradykinin. In basilar
      arteries, relaxations to HN-10200 were augmented by the removal of endothelium,
      whereas relaxations to IBMX were not affected. Relaxations to prostacyclin, SIN
      1, and EDRF were not affected by the presence of phosphodiesterase inhibitors.
      The results of the present study suggest that HN-10200 causes endothelium
      independent relaxations. In addition, it may augment relaxations to prostacyclin
      but does not affect relaxations to EDRF.

PMID- 1382556
TI  - The 1991 Crookshank Lecture of the Royal College of Radiologists, given by Sir
      Donald Acheson, 17 May, 1991. Does cancer control require a national policy?

PMID- 1382557
TI  - Is aggressive surgical palliation of proximal bile duct cancer with involvement
      of both main hepatic ducts worthwhile?
AB  - The only curative treatment for proximal bile duct cancer with involvement of
      both main hepatic ducts is liver transplantation. Most patients do not fulfill
      the requirements for liver transplantation. Our treatment strategy in appropriate
      cases is palliative tumor resection and reconstruction of the biliary passage by
      sutureless bilioenteric anastomosis. We have treated 12 patients, 5 in
      combination with intraluminal and percutaneous radiotherapy. Our results indicate
      that this strategy leads to effective palliation in some cases provided that only
      microscopic residual tumor is left in-situ. Our survival times compare favourably
      with survival after liver transplantation.

PMID- 1382558
TI  - Primary sclerosing cholangitis: palliative surgery or transplantation?

PMID- 1382560
TI  - Different localization of Epstein-Barr virus genome in two subclones of the
      Burkitt lymphoma cell line Namalwa.
AB  - The Epstein-Barr virus genome contained in the Burkitt lymphoma line Namalwa was
      previously localized to the short arm of chromosome 1. Analysis of a different
      subline of the same Namalwa line by means of Southern analysis carried out on
      genomic DNA, as well as in situ hybridization, showed a localization on the X
      chromosome.

PMID- 1382559
TI  - Two malignant peripheral primitive neuroepithelial tumor cell lines established
      from consecutive samples of one patient: characterization and cytogenetic
      analysis.
AB  - A 6-year-old girl presented with a tumor of the right shoulder involving bone,
      adjacent soft tissue, and regional lymph nodes. The conventional histologic
      diagnosis was ambiguous, initially suggesting lymphoma. After relapse on lymphoma
      therapy, reevaluation with additional multiple diagnostic techniques performed on
      the biopsy tissue and on two cell lines derived from the biopsies established the
      diagnosis of a primitive neuroepithelial tumor of bone and soft tissue. This was
      strongly supported by 1) focal rosette formation by the tumor cells and positive
      immunostaining for neuron-specific enolase and synaptophysin, with absent
      staining for leukocyte common antigen; 2) at the ultrastructural level, formation
      of cellular processes containing microtubules, a paucity of neurosecretory
      granules, absence of synaptic junctions, formation of long "intermediate"
      junctions between cells, and, in culture, widespread development of rosettes; 3)
      marked surface positivity to W 6/32 and negativity to HSAN 1.2 antibodies; and 4)
      elevated expression of MYC and lack of overexpression of MYCN oncogenes.
      Numerical and structural abnormalities were present in the karyotype, but the
      expected t(11;22)(q24;q12) was not present in the tumor-involved marrow or in
      either of the established tumor cell lines, although there was an interstitial
      deletion of 11q involving breakpoints in q21 and q23.

PMID- 1382561
TI  - The translocation (1;14)(p34;q11) in human T-cell leukemia: chromosome breakage
      25 kilobase pairs downstream of the TAL1 protooncogene.
AB  - Nearly 30 percent of patients with T-cell acute lymphoblastic leukemia (T-ALL)
      exhibit a tumor-specific rearrangement of the TAL1 gene (also called TCL5 or
      SCL). These rearrangements are generated by either local DNA deletion or a
      (1;14)(p34;q11) chromosome translocation, and they typically result in structural
      alterations of the TAL1 transcription unit. In this report we present a molecular
      characterization of the t(1;14)(p34;q11) from a T-ALL patient. As a consequence
      of the translocation, TAL1 is transposed from its normal position on chromosome 1
      into the T-cell receptor alpha/delta chain locus on chromosome 14. Unlike
      previous cases, the chromosome 1 breakpoint in this patient did not disrupt the
      continuity of the TAL1 transcription unit, but instead occurred approximately 25
      kilobase pairs (kb) downstream of TAL1. This observation suggests that malignant
      alteration of TAL1 can be mediated by long-range cis-activating mechanisms that
      are triggered by DNA rearrangement at a distant site. Genes Chrom Cancer 4:211
      216 (1992).

PMID- 1382562
TI  - Loss of chromosome 3 alleles and multiplication of chromosome 8 alleles in uveal
      melanoma.
AB  - Uveal melanoma is the most frequent primary intraocular tumor. The etiology is
      unknown. Using neutral DNA polymorphisms on chromosomes 2, 3, and 8, we have
      detected loss of chromosome 3 alleles in 8 of 13 tumors and multiplication of
      chromosome 8 alleles in 6 of 11 tumors. No anomalies at a locus on chromosome 2
      were found in 10 of 10 tumors. These results confirm and extend previous
      cytogenetic findings and suggest that a tumor suppressor gene on chromosome 3 and
      an oncogene on chromosome 8 may be involved in the formation or progression of
      this tumor.

PMID- 1382563
TI  - Characterization and molecular analysis of nondisjunction in 18 cases of trisomy
      21 and leukemia.
AB  - We recently began a cytogenetic and molecular study of nondisjunction in leukemic
      Down syndrome individuals to determine whether the mechanism by which the extra
      chromosome 21 originates predisposes the individual to leukemia. In the present
      report, we summarize our observations on 18 patients with trisomy 21 and acute or
      transient leukemia, including 11 patients with acute lymphocytic leukemia, three
      with acute myeloid leukemia, one with B-cell lymphoma, one with acute
      megakaryoblastic leukemia, and two with transient leukemia. Results of DNA marker
      studies of the parental origin of the extra chromosome 21 indicated that 16 of
      the 18 cases (89%) were maternally derived, a percentage similar to that seen
      among nonleukemic Down syndrome patients. We noted that most leukemic Down
      syndrome patients had one locus or more in which parental heterozygosity was
      maintained in the trisomic individual, indicating a meiotic rather than a mitotic
      origin for the trisomy.

PMID- 1382564
TI  - Ordering of six polymorphic DNA markers important in the delineation of 3p
      deletions in neoplasia.
AB  - Using fluorescence in situ hybridisation (FISH) the chromosomal location and
      relative order of six human chromosome 3 probes has been determined. The
      sensitivity of the technique has enabled the relative mapping of probes carrying
      inserts as small as 500 basepairs (bp), thus allowing the following proximal
      distal probe order to be proposed: D3S30 (3p13-14), D3S4 (3p13-14), D3S2 (distal
      3p14), D3S32 (3p21), D3S48E (3p21-23), and D3S11 (3p22-23). These data combined
      with the deletion mapping data of other researchers raise the possibility that
      the loss of more than one region of the short arm of chromosome 3 may be
      important in the development of small cell lung cancer.

PMID- 1382565
TI  - Clonal structural chromosome aberrations in nonneoplastic cells of the skin and
      upper aerodigestive tract.
AB  - Cytogenetic analyses of tumors of the skin and upper aerodigestive tract have
      repeatedly revealed small, pseudodiploid clones characterized by balanced
      structural rearrangements and a high frequency of cells with nonclonal structural
      aberrations. However, the lack of common cytogenetic denominators within the
      different histologic subtypes, the discrepancy between cytogenetic findings and
      data obtained from flow cytometric DNA content studies, and the occasional
      identification of tumors with massively rearranged karyotypes indicate that the
      chromosome rearrangements present in pseudodiploid cells have little to do with
      the tumorigenesis or progression. Further support for this conclusion, and
      indirect evidence that the pseudolipid clones probably do not represent the tumor
      cell populations, derives from the present study in which clonal and nonclonal
      structural rearrangements were also found in short-term cultures from
      nonneoplastic skin and pharyngeal mucosa. It is possible that the aberrations are
      present in subepithelial fibroblast that have accumulated DNA damage due to
      extensive exposure to potentially carcinogenic agents.

PMID- 1382566
TI  - Chromosomal sublocalization of the 2;13 translocation breakpoint in alveolar
      rhabdomyosarcoma.
AB  - A characteristic balanced reciprocal chromosomal translocation [t(2;13)(q35;q14)]
      has been identified in more than 50% of alveolar rhabdomyosarcomas. As the first
      step in characterization of the genes involved in this translocation, we
      constructed somatic cell hybrids that retained either the derivative chromosome 2
      or the derivative chromosome 13 without a normal chromosome 13 homologue. Ten
      linked DNA probes known to be located within bands 13q13-q14 were mapped relative
      to the breakpoint on chromosome 13, allowing localization of the breakpoint
      region between two loci separated by 5.5 cM. A long-range restriction map
      extending approximately 2,300 kb around these loci failed to provide evidence of
      rearrangement. Additionally, we confirmed that the FMS-like tyrosine kinase gene
      (FLT), previously localized to 13q12 by in situ hybridization, is located
      proximal to the breakpoint, and we demonstrated that FLT is not a target for
      disruption by this tumor-specific translocation.

PMID- 1382567
TI  - Retinoblastoma gene deletions in B-cell chronic lymphocytic leukemia.
AB  - Approximately 10% of B-cell chronic lymphocyte leukemia (B-CLL) cases have
      structural chromosomal aberrations involving band 13q14. To evaluate a possible
      role of RBl gene deletions in B-CLL we investigated the malignant cells of 27
      patients by molecular genetic and cytogenetic techniques. Four of the cases had
      chromosomal aberrations that involved 13q14 (including one case with a 13q14
      deletion that was observed in a single metaphase cell), and 11 had other
      chromosomal abnormalities, whereas the malignant cells of 12 patients were either
      cytogenetically normal or failed to divided in vitro. Eight patients (30%) were
      found to have hemizygous deletions of the RBl gene. These cases included all four
      patients with chromosomal changes at 13q14, but also three patients without
      chromosome abnormalities and one case with a chromosomal aberration not involving
      13q. The deletions were interstitial in all cases but one, as defined by probes
      located centromeric and telomeric of the RBl locus. Inactivation of RBl may thus
      be a significant event in the development of some B-CLL clones.

PMID- 1382568
TI  - Cytogenetic analysis by chromosome painting using DOP-PCR amplified flow-sorted
      chromosomes.
AB  - A novel polymerase chain reaction (PCR) technique has been combined with
      chromosome flow sorting to characterise two lymphoblastoid cell lines and one
      medullary thyroid carcinoma cell line carrying translocations close to the locus
      for multiple endocrine neoplasia type 2A (MEN 2A). Five hundred copies of the
      derivative chromosome(s) were flow sorted from each cell line and amplified by
      degenerate oligonucleotide-primed-polymerase chain reaction (DOP-PCR). This
      generated pools of DNA sequences corresponding to the abnormal chromosomes, which
      were then used as probes in fluorescence in situ hybridisation (FISH) experiments
      on normal metaphase cells. The resultant chromosome paints revealed the portions
      of the normal chromosomes related to those involved in the translocations. By
      this technique, translocation breakpoints in bands p15, q11.2, and q21 of
      chromosome 10 were defined in the above cell lines, in two cases refining
      previous cytogenetic data. This study shows that flow sorting of aberrant
      chromosomes and chromosome painting can be used as a rapid aid to cytogenetic
      analysis, particularly in cases of difficult karyotypes, such as tumours.
      Furthermore, the DOP-PCR technique described here will have applications to other
      areas of genome analysis, such as cloning of new markers; its design will allow a
      general and representative amplification to occur from any starting DNA in any
      species.

PMID- 1382569
TI  - Trisomy 5 and trisomy 7 are nonrandom aberrations in pigmented villonodular
      synovitis: confirmation of trisomy 7 in uncultured cells.
AB  - Pigmented villonodular synovitis (PVNS) is a proliferative lesion of disputed
      genesis. Recently, we reported trisomy 7 in short-term cultures of 1 PVNS. In the
      present report, we describe another specimen of PVNS in which 9 of 26 (35
      percent) metaphase cells demonstrated trisomy 7 when analyzed after 3-15 days of
      tissue culture. In situ hybridization analysis, with a biotinylated probe to
      chromosome 7 alpha-satellite DNA, revealed trisomy 7 in 53 of 200 uncultured
      cells from this PVNS sample. Our findings indicate that trisomy 7 is a nonrandom
      aberration that arises in vivo in PVNS.

PMID- 1382570
TI  - Low chromosome number in chromophobe renal cell carcinomas.
AB  - Cytogenetic analysis revealed low chromosome number, telomeric association, and
      pulverisation of chromosomes in three chromophobe renal cell carcinomas. One
      fully karyotyped and a previously published case showed the common loss of
      chromosomes 1, 2, 6, 10, 13, 17, and 21.

PMID- 1382571
TI  - Trisomy 8 in Philadelphia chromosome (Ph1)-negative cells in the course of Ph1
      positive chronic myelocytic leukemia.
AB  - A female patient with chronic myelocytic leukemia (CML) in chronic phase after
      busulfan and interferon treatment had four different cell lines in her bone
      marrow. In addition to cells with a normal karyotype there were cells with the
      Philadelphia chromosome (Ph1), cells with trisomy 8 and Ph1, and cells with
      trisomy 8 as the sole anomaly.

PMID- 1382572
TI  - [Induction of differentiation of human leukemia cells].
AB  - Human myeloid leukemia cells do not differentiate into functional end-cells but
      remain in the proliferation pool. Human cell lines can serve as model for
      hematopoietic cells arrested at different stages of myeloid differentiation and
      helps to dissect the cellular and molecular events involved in leukemogenesis.
      Furthermore, several agents have been identified as inducers of differentiation
      of leukemia cells. Exciting new clinical observation have shown that patients
      with APL respond well to the treatment with all-trans retinoic acid. RAR-alpha
      gene was proved to translocated from chromosome 17 to a locus PML on chromosome
      15. This new chimeric gene, PML-RAR alpha is extremely important to understand
      the leukemogenesis of APL.

PMID- 1382573
TI  - Studies on antitumor effects and mechanism of action of l-hexylcarbamoyl-5
      fluorouracil by DNA/BrdU double staining using flow cytometry.
AB  - An investigation was carried out to elucidate the mechanism of action of the oral
      antitumor agent 1-hexylcarbamoyl-5-fluorouracil (HCFU) by determining its effects
      on the growth and cell cycle of epipharyngeal carcinoma cells (KB cell) by
      DNA/BrdU double staining using flow cytometry (FCM). As a result, it was found
      that HCFU stimulates KB cells in the S phase to proliferate for the first 3 days
      of treatment in a low concentration (8 micrograms/ml) and caused cell
      accumulation in the later G2M phase. On the other hand, when administered in the
      concentration (20 micrograms/ml) that produces a 50 per cent cell kill, as
      determined from the cell growth curve, HCFU appeared to exhibit a cytocidal
      effect by blocking cells in S and G2M for the first 3 days after exposure. It was
      revealed by FCM for the first time that HCFU operates by a similar mechanism to
      that of 5-FU. This method seems to be of significance to therapeutic schemes that
      take into consideration the mechanism of action of antitumor drugs.

PMID- 1382574
TI  - The gene organization of the human beta 7 subunit, the common beta subunit of the
      leukocyte integrins HML-1 and LPAM-1.
AB  - The integrin beta 7 subunit associates with two alternative alpha subunits termed
      alpha HML-1 and alpha 4 to give the lymphocyte activation and homing receptors
      HML-1 and LPAM-1. Overlapping genomic clones that encoded the human beta 7
      subunit gene were isolated from cosmid and phage lambda libraries. The coding
      portion of the gene spanned approximately 10 kb and was composed of 14 exons.
      Exon 1 (123 bp) encoded 5' untranslated sequences; exon 2 (204 bp) encoded the
      initiation codon, signal peptide, and 50 amino acid residues of the N-terminus of
      the mature protein; 7 exons (exons 3-9), ranging in size from 90 bp to 242 bp,
      encoded most of the extracellular domain proximal to the four cysteine-rich
      repeats; the region corresponding to the beta 3 arginine-glycine-aspartic acid
      (RGD)-binding domain was divided amongst exons 4 and 5; the four cysteine-rich
      repeats were encoded by 3 exons (exons 10-12) with intron insertion into the
      first and third repeats; exon 13 (209 bp) provided a spacer between the cysteine
      rich domains and the transmembrane domain; exon 14 (161 bp) encoded the
      transmembrane domain and exactly half of the cytoplasmic domain; the remainder of
      the cytoplasmic domain and most of the 3' untranslated region was contained in
      the largest 313 bp exon 15. Comparison of integrin beta subunit genes revealed
      that the gene organization of beta 7 was almost identical to that of beta 2, but
      had diverged from that of beta 3. Amplification of integrin DNAs directly from
      genomic DNA, using PCR primers based on beta subunit consensus sequences
      corresponding to the beta 3 RGD-binding domain, yielded partial gene sequences
      for the beta 3, beta 5, and beta 6 subunits only. Inspection of the amplified
      sequences revealed that, as for beta 3, the regions in beta 5 and beta 6
      corresponding to the beta 3 RGD-binding domain lacked the intron present in beta
      7, beta 1, and beta 2, which divides this region in beta 2 into two subdomains
      that contribute to subunit assembly. This study provides genetic evidence for at
      least two major branches to the integrin beta subunit evolutionary tree, with
      beta 7, beta 2, and probably beta 1 in one branch, and the cytoadhesin beta 3 and
      probably also beta 5 and beta 6 in the other.

PMID- 1382575
TI  - Midpregnancy plasma zinc in normal and growth retarded fetuses--a preliminary
      study.
AB  - OBJECTIVE: To determine plasma zinc concentrations in normally and abnormally
      growing fetuses. DESIGN: Prospective observational study. SETTING: Fetal Medicine
      Unit, Queen Charlotte's Maternity Hospital. SUBJECTS: 53 pregnant women attending
      for fetal blood sampling at between 18 and 40 weeks gestation. 27 fetuses were
      normal (central group), 11 fetuses were growth retarded and 15 were malformed.
      MAIN OUTCOME MEASURES: Plasma zinc concentrations in maternal and fetal blood at
      time of fetal blood sampling. RESULTS: In normally growing fetuses, between 18
      and 40 weeks gestation, there was no fall in maternal plasma zinc concentration;
      the fetal level fell by 36%. In 10 fetuses with symmetrical growth retardation,
      plasma zinc concentration tended to be low, but was not significantly different
      from that in the normal control fetuses. CONCLUSION: The results suggest that (i)
      placental transfer of zinc is an uphill secretory process and that it is a rate
      limiting step in the accumulation of zinc by the fetus and (ii) in fetuses with
      symmetrical intrauterine growth retardation, a low plasma zinc is probably a
      parallel phenomenon and not necessarily an aetiological factor.

PMID- 1382577
TI  - Solution structure of an unusually stable RNA tetraplex containing G- and U
      quartet structures.
AB  - A model for the solution structure of an RNA tetraplex, (rUGGGGU)4, has been
      obtained by two-dimensional NMR spectroscopy and molecular dynamics. The molecule
      is parallel stranded and Hoogsteen base-paired in 50 mM KCl, and it is so stable
      that three of its six imino protons have exchange half-lives measured in days at
      40 degrees C. The tetraplex is stabilized by base stacking and by the hydrogen
      bonds in four G quartets and at least one U quartet. This is the first indication
      of the existence of U-quartet structures of which we are aware.

PMID- 1382576
TI  - In situ immunohistochemical analysis of cell adhesion molecules on human corneal
      endothelial cells.
AB  - Interaction of leucocytes with human corneal endothelial cells (HCECs) can be
      observed in several clinicopathological conditions, such as uveitis, keratitis,
      and corneal graft rejection. Since leucocyte-endothelial cell interactions
      involve various adhesion receptors we have analysed the expression and
      distribution pattern of the neural cell adhesion molecule (NCAM), the
      intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule-1
      (VCAM-1), the endothelial leucocyte adhesion molecule-1 (ELAM-1), and the cluster
      of differentiation antigen-44 (CD44) on flat preparations of normal and organ
      cultured HCECs. NCAM and ICAM were constitutively expressed on HCECs whereas VCAM
      1, ELAM-1, and CD44 were absent from normal HCECs. However flat mounts of HCECs
      from organ-culture preserved corneas showed a mosaic-like distribution pattern of
      VCAM-1 and ELAM-1 positive cells and garland-like clusters of CD44 positive
      cells. We suggest that modulation of ELAM-1, VCAM-1, and CD44 expression on HCECs
      may contribute to the regulation of leucocytes-HCECs interaction in the case of
      anterior segment inflammation.

PMID- 1382578
TI  - Cross-linking activity of the 14-kilodalton beta-galactoside-specific vertebrate
      lectin with asialofetuin: comparison with several galactose-specific plant
      lectins.
AB  - We have previously shown that plant lectins with a wide range of carbohydrate
      binding specificities can bind and cross-link (precipitate) specific
      multiantennary oligosaccharides and glycopeptides [cf. Bhattacharyya, L., Fant,
      J., Lonn, H., & Brewer, C. F. (1990) Biochemistry 29, 7523-7530]. This leads to a
      new source of binding specificity: namely, the formation of homogeneous cross
      linked lattices between lectins and carbohydrates. Recently, we have demonstrated
      the existence of highly ordered cross-linked lattices that form between the D
      Man/D-Glc-specific plant lectin concanavalin A and the soybean agglutinin which
      is a tetrameric glycoprotein possessing a single Man9 oligomannose chain per
      monomer [Khan, M. I., Mandal, D. K., & Brewer, C. F. (1991) Carbohydr. Res. 213,
      69-77]. In the present study, we have compared the ability of the 14-kDa beta
      galactoside-specific lectin from calf spleen, a dimeric S-type animal lectin, and
      several galactose-specific plant lectins from Erythrina indica, Erythrina
      cristagalli, and Glycine max (soybean agglutinin) to form specific cross-linked
      complexes with asialofetuin (ASF), a 48-kDa monomeric glycoprotein, using
      quantitative precipitation analyses. The results show the formation of 1:9 and
      1:3 stoichiometric cross-linked complexes (per monomer) of ASF to the 14-kDa
      lectin, depending on their relative ratio in solution. Evidence indicates that
      the three triantennary N-linked complex-type oligosaccharide chains of ASF
      mediate the cross-linking interactions and that each chain expresses either
      trivalency in the 1:9 cross-linked complex or univalency in the 1:3
      complex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382579
TI  - Spectroscopic study of the activation and oligomerization of the channel-forming
      toxin aerolysin: identification of the site of proteolytic activation.
AB  - The channel-forming protein aerolysin is secreted as a protoxin which can be
      activated by proteolytic removal of a C-terminal peptide. The activation and
      subsequent oligomerization of aerolysin were studied using a variety of
      spectroscopic techniques. Mass spectrometric determination of the molecular
      weights of proaerolysin and aerolysin permitted identification of the sites at
      which the protoxin is processed by trypsin and chymotrypsin. The results of far-
      and near-UV circular dichroism measurements indicated that processing with
      trypsin does not lead to major changes in secondary or tertiary structure of the
      protein. An increase in tryptophan fluorescence intensity and a small red shift
      in the maximum emission wavelength of tryptophans could be observed, suggesting
      that there is a change in the environment of some of the tryptophans. There was
      also a dramatic increase in the binding of the hydrophobic fluorescent probe 1
      anilino-8-naphthalenesulfonate during activation, leading us to conclude that a
      hydrophobic region in the protein is exposed by trypsin treatment. Using
      measurements of light scattering, various parameters influencing oligomerisation
      of trypsin-activated aerolysin were determined. Oligomerization rates were found
      to increase with the concentration of aerolysin, whereas they decreased with
      increasing ionic strength.

PMID- 1382580
TI  - A conformational rearrangement in gramicidin A: from a double-stranded left
      handed to a single-stranded right-handed helix.
AB  - A conformational transition is described for the polypeptide, gramicidin A, in
      which a dimer that forms a left-handed intertwined antiparallel helix is
      converted to a single-stranded amino terminus to amino terminus right-handed
      helix. The starting structure is determined here by solution NMR methods while
      reference is made to the well-established folding motif of gramicidin in a lipid
      bilayer for the ultimate conformation of this transition. Furthermore, an organic
      solvent system of benzene and ethanol in which gramicidin has a unique
      conformation is identified. This conformation is shown to be very similar to that
      derived from X-ray diffraction of crystals prepared from a similar solvent
      system.

PMID- 1382581
TI  - Ca(2+)-calmodulin regulated effectors of microtubule stability in bovine brain.
AB  - Stable microtubules (as defined by resistance to Ca2+, drug or cold temperature
      induced disassembly) form in abundance during tubulin assembly in brain crude
      extracts. We have previously shown that, in rat brain crude extracts, all
      microtubule stabilizing activity could be ascribed to a single Ca(2+)-calmodulin
      binding and Ca(2+)-calmodulin regulated protein, called "stable tubule only
      polypeptide", STOP145 [Pirollet, F., Rauch, C. T., Job, D., & Margolis, R. L.
      (1989) Biochemistry 28, 835-842]. We have now performed an exhaustive study of
      STOP-like effectors in bovine brain high-speed supernatants. All activity binds
      to cation exchangers and to Ca(2+)-calmodulin affinity columns. The activity can
      be resolved into two peaks on sizing columns. The first eluted peak contains a
      prominent 220-kDa protein. The second peak contains an apparently homogeneous 20
      kDa polypeptide. A monoclonal antibody specific to rat brain STOP145 recognizes
      the 220-kDa protein, but not the 20-kDa species. The 220-kDa protein can be
      purified on a STOP antibody column and accounts for the bulk of stabilizing
      activity in the first peak. The 20-kDa protein does not bind to STOP antibody
      affinity columns. Sequence analysis of oligopeptide fragments of the 20-kDa
      protein shows 100% homology with bovine myelin basic protein (MBP). Anti-MBP
      antibodies recognize the 20-kDa, but not the 220-kDa species. We conclude that
      the 220-kDa protein is the bovine equivalent to rat brain STOP145 and that the 20
      kDa species is MBP. Microtubule stabilization by MBP and STOP220 is abolished in
      the presence of Ca(2+)-calmodulin, and inhibition curves are similar for both
      proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382582
TI  - Thermodynamics of single-stranded RNA binding to oligolysines containing
      tryptophan.
AB  - The equilibrium binding to the synthetic RNA poly(U) of a series of oligolysines
      containing one, two, or three tryptophans has been examined as a function of pH,
      monovalent salt concentration (MX), temperature, and Mg2+. Oligopeptides
      containing lysine (K) and tryptophan (W) of the type KWKp-NH2 and KWKp-CO2 (p = 1
      8), as well as peptides containing additional tryptophans or glycines, were
      studied by monitoring the quenching of the peptide tryptophan fluorescence upon
      binding poly(U). Equilibrium association constants, K(obs), and the thermodynamic
      quantities delta G(o)obs, delta H(o)obs, and delta S(o)obs describing peptide
      poly(U) binding were measured as well as their dependences on monovalent salt
      concentration, temperature, and pH. In all cases, K(obs) decreases significantly
      with increasing monovalent salt concentration, with (delta log K(obs)/delta log
      [K+]) = -0.74 (+/- 0.04)z, independent of temperature and salt concentration,
      where z is the net positive charge on the peptide. The origin of these salt
      effects is entropic, consistent with the release of counterions from the poly(U)
      upon formation of the complex. Upon extrapolation to 1 M K+, the value of delta
      G(o)obs is observed to be near zero for all oligolysines binding to poly(U),
      supporting the conclusion that these complexes are stabilized at lower salt
      concentrations due to the increase in entropy accompanying the release of
      monovalent counterions from the poly(U). Only the net peptide charge appears to
      influence the thermodynamics of these interactions, since no effects of peptide
      charge distribution were observed. The binding of poly(U) to the monotryptophan
      peptides displays interesting behavior as a function of the peptide charge. The
      extent of tryptophan fluorescence quenching, Qmax, is dependent upon the peptide
      charge for z less than or equal to +4, and the value of Qmax correlates with z
      dependent changes in delta H(o)obs and delta S(o)obs(1 M K+), whereas for z
      greater than or equal to +4, Qmax, delta H(o)obs, and delta S(o)obs (1 M K+) are
      constant. The correlation between Qmax and delta H(o)obs and delta S(o)obs(1 M
      K+) suggests a context (peptide charge)-dependence of the interaction of the
      peptide tryptophan with poly(U). However the interaction of the peptide
      tryptophan does not contribute substantially to delta G(o)obs for any of the
      peptides, independent of z, due to enthalpy-entropy compensations. Each of the
      tryptophans in multiple Trp-containing peptides appear to bind to poly(U)
      independently, with delta H(o)Trp = -2.9 +/- 0.7, although delta G(o)Trp is near
      zero due to enthalpy-entropy compensations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1382583
TI  - Structure of alpha 2-macroglobulin-protease complexes. Methylamine competition
      shows that proteases bridge two disulfide-bonded half-molecules.
AB  - alpha 2-Macroglobulin (alpha 2M) forms several different covalent complexes with
      proteases. These include unusual forms in which more than one of the four
      identical subunits of alpha 2M are cross-linked by amide bonds to more than one
      lysyl amino group of the bound protease. The structure of these complexes and the
      question of how the identical subunits are arranged to form two protease binding
      sites are matters of current controversy. The 185-kDa subunits are arranged into
      two disulfide-bonded half-molecules which are, in turn, noncovalently associated.
      We have provided evidence that, in the major multivalent cross-linked form,
      proteases can span the two half-molecules, forming a covalently bonded tetramer
      [Wang, D., Yuan, A. I., & Feinman, R. D. (1984) Biochemistry 23, 2807-2811]. An
      alternative theory has recently been proposed in which the major high molecular
      weight form has two bonds to protease that are within half-molecules--a
      multivalent cross-linked dimer [Sottrup-Jensen, L., Hansen, H. F., Pedersen, H.
      S., & Kristensen, L. (1990) J. Biol. Chem. 265, 17727-17737]. To resolve this
      conflict, experiments were carried out to determine the structure of one of the
      high molecular weight bands (band 3) seen on SDS-PAGE. Band 3 has anomalous
      migration, corresponding to markers of apparent molecular mass of 550 kDa
      (between the tetramer and dimer). In the experiments described here, reactions of
      thrombin with alpha 2M were run in the presence of methylamine, which competes
      for one of the two thrombin-alpha 2M covalent bonds.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382584
TI  - Insulin stimulates tyrosine phosphorylation of multiple high molecular weight
      substrates in Fao hepatoma cells.
AB  - Insulin rapidly stimulates tyrosine phosphorylation of cellular proteins which
      migrate between 165 and 190 kDa during SDS-PAGE. These proteins, collectively
      called pp185, were originally found in anti-phosphotyrosine antibody (alpha PY)
      immunoprecipitates from insulin-stimulated Fao rat hepatoma cells. Recently, we
      purified and cloned IRS-1, one of the phosphoproteins that binds to alpha PY and
      migrates near 180 kDa following insulin stimulation of rat liver [Sun, X. J., et
      al. (1991) Nature 352, 73-77]. IRS-1 and pp185 undergo tyrosine phosphorylation
      immediately after insulin stimulation and show an insulin dose response similar
      to that of insulin receptor autophosphorylation. However, IRS-1 was consistently
      10 kDa smaller than the apparent molecular mass of pp185. The pp185 contained
      some immunoblottable IRS-1; however, cell lysates depleted of IRS-1 with anti-IRS
      1 antibody still contained the high molecular weight forms of pp185 (HMW-pp185).
      Furthermore, the tryptic phosphopeptide map of IRS-1 was distinct from that of
      HMW-pp185, suggesting that at least two substrates migrate in this region during
      SDS-PAGE. Moreover, the phosphatidylinositol 3'-kinase and its 85-kDa associated
      protein (p85) bound to IRS-1 in Fao cells, but weakly or not at all to HMW-pp185.
      Our results show that Fao cells contain at least two insulin receptor substrates,
      IRS-1 and HMW-pp185, which may play unique roles in insulin signal transmission.

PMID- 1382585
TI  - Interaction of cytochrome c with cytochrome c oxidase studied by monoclonal
      antibodies and a protein modifying reagent.
AB  - C/57 black mice were immunized with beef heart cytochrome c oxidase, generating
      48 hybrid cell lines that secrete antibodies against the different subunits of
      the enzyme. Immunoblot analysis showed reactions with 7 of the 13 subunits. Among
      the monoclonal antibodies produced, only those to subunit II gave significant
      inhibition; these inhibited the enzyme activity completely and prevented
      cytochrome c binding to the enzyme. Epitope mapping studies indicate that a
      peptide including residues 200-227 reacts with the antibody, suggesting that the
      C-terminus of the protein is essential for the binding of this antibody. The
      carboxyl modifying reagent 1-ethyl-3-[3-(trimethylammonio)propyl]carbodiimide
      (ETC) was chosen to investigate further the relationship between antibody and
      cytochrome c binding domains. ETC caused 50% inhibition of the enzyme activity
      with a first-order time during the first 20 min; a slower reaction over 3 h
      resulted in 90% inhibition. Cytochrome c binding to the oxidase was inhibited to
      a similar extent as cytochrome c oxidation, and protection against both effects
      was afforded by the presence of cytochrome c during ETC modification. Anion
      exchange of FPLC of the modified forms of cytochrome oxidase revealed extensive
      inhomogeneity, indicating random derivatization of a number of different
      carboxyls even during the first-order reaction, and precluding identification of
      carboxyl residues related to a specific phase of the reaction. Cytochrome c and
      the subunit II-specific antibody protected against radioactive labeling of
      subunit II by ETC in the presence of [14C]glycine ethyl ester, demonstrating that
      the antibody and cytochrome c occupy significant and overlapping areas on the
      subunit II surface.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382586
TI  - Novel sulfated ligands for the cell adhesion molecule E-selectin revealed by the
      neoglycolipid technology among O-linked oligosaccharides on an ovarian
      cystadenoma glycoprotein.
AB  - E-selectin is the inducible adhesion protein on the surface of endothelial cells
      which has a crucial role in the initial stages of recruitment of leucocytes to
      sites of inflammation. In addition, it is almost certainly involved in tumor cell
      adhesion and metastasis. This report is concerned with identification of a new
      class of oligosaccharide ligand--sulfate-containing--for the human E-selectin
      molecule from among oligosaccharides on an ovarian cystadenoma glycoprotein. This
      has been achieved by application of the neoglycolipid technology to
      oligosaccharides released from the glycoprotein by mild alkaline beta
      elimination. Oligosaccharides were conjugated to lipid, resolved by thin-layer
      chromatography, and tested for binding by Chinese hamster ovary cells which had
      been transfected to express the full-length E-selectin molecule. Several
      components with strong E-selectin binding activity were revealed among acidic
      oligosaccharides. The smallest among these was identified by liquid secondary ion
      mass spectrometric analysis of the neoglycolipid, in conjunction with methylation
      analysis of the purified oligosaccharide preparation as an equimolar mixture of
      the Le(a)- and Le(x)/SSEA-1-type fucotetrasaccharides sulfated at position 3 of
      outer galactose: [formula: see text] To our knowledge this is the first report of
      a sulfofucooligosaccharide ligand for E-selectin. The binding activity is
      substantially greater than those of lipid-linked Le(a) and Le(x)/SSEA-1 sequences
      and is at least equal to that of the 3'-sialyl-Le(x)/SSEA-1 glycolipid analogue.

PMID- 1382587
TI  - Analysis of the backbone dynamics of the ribonuclease H domain of the human
      immunodeficiency virus reverse transcriptase using 15N relaxation measurements.
AB  - The backbone dynamics of the uniformly 15N-labeled ribonuclease H (RNase H)
      domain of human immunodeficiency virus (HIV-1) reverse transcriptase have been
      investigated using two-dimensional inverse-detected heteronuclear 15N-1HNMR
      spectroscopy. 15N T1, T2, and nuclear Overhauser enhancement (NOE) data were
      obtained for 107 out of a total of 134 backbone amide groups. The overall
      rotational correlation time (tau R) for the protein at 26 degrees C is 10.4 ns.
      The backbone N-H vectors for all the measurable residues exhibit very fast
      motions on a time scale of less than or equal to 20 ps. The 15N relaxation data
      for only 14 residues can be explained by this single internal motion alone. A
      further 39 residues display a second motion on a time scale ranging from 28.8 ps
      to 3.9 ns, while another 15 residues are characterized by an additional motion on
      the 170-ns to 2.25-ms time scale resulting in 15N T2 exchange line broadening.
      There are 39 residues that exhibit both the additional 15N T2 exchange line
      broadening and the slow (28.8 ps-3.9 ns) internal motion. Thus, the RNase H
      domain experiences extensive mobility throughout its structure as evidenced by
      the 93 residues which exhibit multiple modes of motion. Distinctly mobile regions
      of the protein are identified by large decreases in the overall order parameter
      (S2) and correspond to the C-terminal residues and the loop regions between beta
      strands beta 1 and beta 2 and between alpha-helix alpha B and beta-strand beta
      4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382588
TI  - Identification of a second promoter which drives the expression of gamma-glutamyl
      transpeptidase in rat kidney and epididymis.
AB  - In rat, gamma-glutamyl transpeptidase (GGT) is encoded by multiple mRNAs (mRNAI,
      mRNAII, mRNAIII, and mRNAIV) that differ only in their 5' untranslated regions
      and are transcribed from a single-copy gene. Using oligonucleotides designed from
      the 5' untranslated sequences of the GGT mRNAII and mRNAIII, we amplified a 3.4
      kb genomic sequence which contains the promoter region for mRNAII. The sequence
      flanking the two initiation start sites for mRNAII contains consensus motifs for
      several potential regulatory proteins and a TATA-like element at the expected
      position 26 bp upstream from the predominant start site. The sequence from
      positions -528 to +72 associated with the chloramphenicol acetyltransferase (CAT)
      reporter gene drives a promoter activity in LLC-PK1, a pig kidney cell line.
      Deletion analysis revealed that the region from nucleotides -528 to -322 mediates
      an activation of the promoter activity, whereas the sequence from -322 to -114
      has a negative effect. Furthermore, the structural organization of the 5' end of
      the GGT gene reveals that the GGT mRNAIII is transcribed from a third promoter
      located upstream from the promoter II on the GGT gene. By Northern blot analysis,
      the promoter II was found to be expressed only in the kidney and in the
      epididymis. We also identified two new mRNA species which are expressed in the H5
      hepatoma cells. Therefore, the GGT gene expression reveals a strong tissue- or
      cell-specific pattern which is based on the transcription of several mRNA species
      from multiple promoters.

PMID- 1382589
TI  - Secondary structure of the pentraxin female protein in water determined by
      infrared spectroscopy: effects of calcium and phosphorylcholine.
AB  - The secondary structure of hamster female protein in aqueous solutions in the
      presence or absence of calcium and phosphorylcholine has been investigated using
      Fourier transform infrared spectroscopy. Our present studies provide the first
      evaluation of the secondary structure of FP and its calcium- and
      phosphorylcholine-dependent conformational changes. Quantitative analysis
      indicated that FP is composed of 50% beta-sheet, 11% alpha-helix, 29% beta-turn,
      and 10% random structures. Calcium- and phosphorylcholine-dependent infrared
      spectral changes were observed in regions assigned to beta-sheet, alpha-helix,
      turn, and random structures. The infrared-based secondary structure compositions
      were used as constraints to compute theoretical locations for the different
      secondary structures along the amino acid sequence of the FP protein. Two
      putative calcium-binding sites were proposed for FP (residues 93-109 and 150-168)
      as well as other members of the pentraxin family on the basis of the theoretical
      secondary structure predictions and the similarity in sequence between the
      pentraxins and EF-hand calcium-binding proteins. The changes in protein
      conformation detected upon binding of calcium and phosphorylcholine provide a
      mechanism for the effects of these ligands on physiologically important
      properties of the protein, e.g., activation of complement and association with
      amyloids.

PMID- 1382590
TI  - Fidelity of the RNA-dependent DNA synthesis exhibited by the reverse
      transcriptases of human immunodeficiency virus types 1 and 2 and of murine
      leukemia virus: mispair extension frequencies.
AB  - Human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2, respectively)
      exhibit extensive genetic variations. It was postulated that much of this genetic
      variability stems from the low fidelity of the reverse transcription step. Both
      HIV reverse transcriptases (RTs) were shown to be particularly error-prone during
      the in vitro DNA-dependent DNA synthesis relative to other retroviral RTs.
      Extension of mismatched 3'-termini of the primer DNA was shown to be a major
      determinant in the infidelity of HIV RTs. However, reverse transcriptases
      generally exhibit dual template specificities. Therefore, we determined in the
      current study the fidelity of RNA-dependent DNA synthesis catalyzed in vitro by
      the RTs of HIV-1 and HIV-2 in comparison with that of murine leukemia virus (MLV)
      RT. Consequently, we examined the ability of these enzymes to extend preformed 3'
      terminal A.A, A.C, and A.G mispairs by quantitating the amount and length of
      extended primers in a primer extension assay using ribosomal RNA as a template.
      The results demonstrate that the three RTs studied exhibited efficient extensions
      from 3'-terminal mispairs with a specificity of A.C greater than A.A greater than
      A.G. Nevertheless, the HIV RTs are qualitatively as well as quantitatively more
      error-prone than MLV RT. The mispair extension efficiency appears to be affected
      mainly by the increase of apparent Km values, rather than by the change in Vmax
      values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382591
TI  - Long-range changes in a protein antigen due to antigen-antibody interaction.
AB  - Amide exchange kinetics were used to probe the conformation of hen egg-white
      lysozyme complexed with the anti-lysozyme monoclonal antibody HyHEL-5. Following
      the technique developed by Paterson et al. [(1990) Science 249, 755-759] we used
      two-dimensional NMR to measure amide exchange kinetics of the lysozyme amide
      protons in the lysozyme-antibody complex. A total of 15 amide protons showed
      altered exchange kinetics in the presence of the complex. Five of these 15
      protons reside on residues that are found within the epitope as defined by X-ray
      crystallography. Five residues are located at the perimeter of the epitope. The
      remaining five residues are removed from the epitope. The perturbation of amide
      exchange rates at sites distant from the epitope indicates that the formation of
      antigen-antibody complexes can produce changes in the antigen at sites that are
      quite distant from the structural epitope.

PMID- 1382593
TI  - Ascorbate both activates and inactivates bleomycin by free radical generation.
AB  - The chemotherapeutic agent bleomycin (BLM) is activated by reducing agents to
      break isolated DNA. Paradoxically, these same reducing agents protect cellular
      DNA from BLM damage. To resolve this paradox, we have examined the reaction of
      FeIIIBLM with DNA in the presence of ascorbate. As expected, ascorbate augments
      FeIIIBLM-induced DNA damage. However, when ascorbate is added to FeIIIBLM prior
      to exposure to DNA, a redox-inactive BLM is produced in a reaction that generates
      the ascorbyl radical. This reaction occurs in both ascorbate-supplemented buffer
      and unsupplemented plasma. In buffered solution, this reaction was found to be
      stoichiometric; for each mole of BLM present, 6.9 mol of ascorbate was oxidized
      and 4.7 mol of oxygen was consumed. Iron was found to serve only as a catalyst
      for the reaction. These data suggest that both activation of BLM and the
      generation of redox-inactive BLM occur via the same reaction and that BLM-induced
      DNA damage depends upon BLM reaching DNA prior to its interaction with reducing
      agents.

PMID- 1382592
TI  - A model for the role of multiple cysteine residues involved in ribonucleotide
      reduction: amazing and still confusing.
AB  - Ribonucleotide reductase from Escherichia coli catalyzes the conversion of
      nucleotides to deoxynucleotides. Multiple cysteins have been postulated to play a
      key role in this process. To test the role of various cysteines in nucleotide
      reduction, a variety of single and double mutants of the R1 subunit were
      prepared: C754S, C759S, C754-759S, C462S, C462A, C230S, and C292S. Due to the
      expression system, each mutant contains small amounts of contaminating wt-R1
      (estimated to be 1.5-3% based on activity). An epitope tagging method in
      conjunction with anion exchange chromatography was used to partially resolve the
      mutant R1 from the wt-R1. The interaction of these mutants with the normal
      substrate was studied, which allowed a model to be proposed in which five
      cysteines of the R1 subunit of RDPR play a role in catalysis. C754S and C759S R1s
      catalyze CDP formation at rates similar to wt-R1 when DTT is used as a reductant.
      However, when thioredoxin (TR)/thioredoxin reductase (TRR)/NADPH is used as
      reductant, the rates of dNDP production are similar to those expected for
      contaminating wt-R1 present as a heterodimer with the mutant. The impaired nature
      of these mutants with respect to reduction by TR suggests that their function is
      to transfer reducing equivalents from TR to the active site disulfide of R1
      produced during NDP reduction. Single-turnover experiments, designed to avoid the
      problem of contaminating wt-R1, also support this role for C754 and C759. The
      double serine mutant of 754 and 759 has catalytic activity with DTT that is one
      third the rate of wt-R1 with thioredoxin. C225 and C462 are thought to be the
      active site cysteines oxidized concomitantly with NDP reduction. Conversion of
      these cysteines to serines results in R1 mutants which convert the normal
      substrate into a mechanism-based inhibitor. C462SR1 upon incubation with R2 and
      [3'-3H,U-14C]UDP results in uracil release, 3H2O production, 3H,14C-labeled
      protein which has an absorbance change at 320 nm, and slow loss of the tyrosyl
      radical on R2. The isotope effect (kH/k3H) on 3' carbon-hydrogen bond cleavage is
      1.7. This sequence of events is independent of the reductant, consistent with the
      postulate that C462 is an active site thiol. The C462AR1 has properties similar
      to C462SR1. Several additional mutant R1s, C230SR1, and C292SR1 were shown to
      have activities similar to wt-R1 with both TR/TRR/NADPH and DTT.

PMID- 1382594
TI  - Molecular dynamics simulation of solvated protein at high pressure.
AB  - We have completed a molecular dynamics simulation of protein (bovine pancreatic
      trypsin inhibitor, BPTI) in solution at high pressure (10 kbar). The structural
      and energetic effects of the application of high pressure to solvated protein are
      analyzed by comparing the results of the high-pressure simulation with a
      corresponding simulation at low pressure. The volume of the simulation cell
      containing one protein molecule plus 2943 water molecules decreases by 24.7% at
      high pressure. This corresponds to a compressibility for the protein solution of
      beta = 1.8 x 10(-2) kbar-1. The compressibility of the protein is estimated to be
      about one-tenth that of bulk water, while the protein hydration layer water is
      found to have a greater compressibility as compared to the bulk, especially for
      water associated with hydrophobic groups. The radius of gyration of BPTI
      decreases by 2% and there is a one third decrease in the protein backbone atomic
      fluctuations at high pressure. We have analyzed pressure effects on the hydration
      energy of the protein. The total hydration energy is slightly (4%) more favorable
      at high pressure even though the surface accessibility of the protein has
      decreased by a corresponding amount. Large pressure-induced changes in the
      structure of the hydration shell are observed. Overall, the solvation shell
      waters appear more ordered at high pressure; the pressure-induced ordering is
      greatest for nonpolar surface groups. We do not observe evidence of pressure
      induced unfolding of the protein over the 100-ps duration of the high-pressure
      simulation. This is consistent with the results of high-pressure optical
      experiments on BPTI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382595
TI  - Inhibition of SH2 domain/phosphoprotein association by a nonhydrolyzable
      phosphonopeptide.
AB  - Using the association between the pp60c-src/polyoma virus middle T antigen (mT)
      complex and phosphatidylinositol 3'-kinase (PI 3-kinase) as a prototype for
      phosphoprotein-SH2 domain interactions, we tested whether a nonhydrolyzable
      phosphonopeptide would inhibit association. (Phosphonomethyl)-phenylalanine (Pmp)
      is a nonnatural analogue of phosphotyrosine in which the > C-O-PO3H2 moiety is
      replaced by > C-CH2-PO3H2. We synthesized a 13 amino acid phosphonopeptide (mT
      Pmp315), a related phosphopeptide (mT-pY315), and an unmodified sequence (mT
      Y315), all corresponding to the pp60c-src-phosphorylated site of the mT which is
      within a YMXM motif common to proteins that bind to and activate PI 3-kinase.
      Only the phosphonopeptide persistently blocked the in vitro association of the
      baculovirus-expressed pp60c-src/mT complex with cytosolic PI 3-kinase activity.
      Sustained inhibition of association by the phosphopeptide required the additional
      presence of vanadate, a potent protein tyrosine phosphatase (PTPase) inhibitor.
      The phosphopeptide and L-phosphonopeptide bound tightly (KD approximately 10-20
      nM) and specifically to isolated SH2 domains of PI 3-kinase p85, demonstrating
      that the mechanism of inhibited association is competitive binding to PI 3-kinase
      SH2 domains. We conclude that the appropriate phosphonopeptide sequence inhibits
      the interaction between a tyrosine-phosphorylated protein and a cognate SH2
      domain-containing protein and is resistant to the actions of PTPases.
      Proteolytically stable phosphonopeptide derivatives should be useful inhibitors
      of protein-protein interactions when introduced into cells and may provide a
      basis for the rational design of a new class of chemotherapeutic agent.

PMID- 1382596
TI  - Purification and characterization of active and latent forms of recombinant
      plasminogen activator inhibitor 1 produced in Escherichia coli.
AB  - Plasminogen activator inhibitor 1 (PAI-1), the principal physiological inhibitor
      of tissue plasminogen activator (tPA), is a protein of 379 amino acids and
      belongs to the SERPIN family of serine protease inhibitors. We have previously
      described methods to express [Sisk et al. (1990) Gene 96, 305-309] and purify
      [Reilly et al. (1990) J. Biol. Chem. 265, 9570-9574] a highly active form of the
      protein in substantial amounts, from Escherichia coli. Further analyses of this
      material showed the presence of small but significant amounts of latent rPAI-1.
      The present paper describes for the first time purification of latent and active
      forms of rPAI-1 from a single preparation, as well as the functional and
      structural characteristics of the two forms. Latent rPAI-1, which has properties
      similar to the latent forms described by other groups, was separated from active
      rPAI-1 by high-resolution ion-exchange chromatography or by affinity
      chromatography using immobilized anhydrotrypsin. It had low intrinsic activity (<
      5% of active rPAI-1) and was partially reactivated by guanidine hydrochloride
      treatment or by incubation with vitronectin. Conversion of the active rPAI-1 to
      the latent form was influenced by temperature and additives including sucrose,
      EDTA, and arginine. Active and latent rPAI-1 did not show any obvious differences
      in their primary structures and displayed remarkably similar secondary structures
      as determined by circular dichroism spectral analyses. However, they did exhibit
      differences in tryptophan fluorescence, suggesting tertiary structural
      differences between the two forms.

PMID- 1382598
TI  - Regulation of phosphate transport by second messengers in capillaries of the
      blood-brain barrier.
AB  - Regulation of phosphate uptake by the blood-brain barrier was studied in isolated
      bovine capillaries. Dibutyryl cAMP, in the presence of 3-isobutylmethylxanthine,
      resulted in a dose-dependent inhibition of phosphate uptake. Phosphate influx,
      with or without 3-isobutylmethylxanthine, was not different. Inhibition of
      phosphate uptake was also observed when capillaries were preincubated with
      isoproterenol, parathyroid hormone, insulin and acidic or basic fibroblast growth
      factors. Treatment of capillaries with vasoactive intestinal peptide,
      prostaglandin E1, angiotensin II, epidermal growth factor and phorbol esters did
      not affect phosphate transport. Endothelin I increased phosphate uptake by 15%.
      Preincubation with cholera toxin also resulted in a dose-dependent decrease in
      phosphate uptake. In addition, pertussis toxin inhibited phosphate transport by
      29%, but only in the presence of 3-isobutylmethylxanthine. These results
      demonstrate that generation of second messengers, following receptor stimulation,
      can induce physiological effects on capillary phosphate influx and suggest that G
      proteins may modulate this transport.

PMID- 1382597
TI  - Determination of rate constants for nucleotide dissociation from Na,K-ATPase.
AB  - A method for determining individual rate constants for nucleotide binding to and
      dissociation from membrane bound pig kidney Na,K-ATPase is presented. The method
      involves determination of the rate of relaxation when Na,K-ATPase in the presence
      of eosin is mixed with ADP or ATP in a stopped-flow fluorescence apparatus. It is
      shown that the nucleotide dependence of this rate of relaxation--taken together
      with measured equilibrium binding values for eosin and ADP--makes possible a
      reasonably reliable determination of the rate constant for dissociation of
      nucleotide, i.e., determination of the rate constant k-1 in the following model
      (where E denotes Na,K-ATPase): [formula: see text] All experiments are carried
      out at about 4 degrees C in a buffer containing 200 mM sucrose, 10 mM EDTA, 25 mM
      Tris and 73 mM NaCl (pH 7.4). Values obtained for the rate constants for
      dissociation are about 6 s-1 for ADP and 2-3 s-1 for ATP.

PMID- 1382599
TI  - Interaction of sulfhydryl reagents with A-type channels of Lymnaea neurons.
AB  - The effect of sulfhydryl reagents on macroscopic inactivation of A-current in
      internally perfused Lymnaea neurons under voltage-clamp conditions was
      investigated. It was found that the binding of Hg2+ rather than PHMB with channel
      proteins resulted in a strong decrease of the peak current and the inactivation
      rate. Hg2+ markedly influenced the steady-state inactivation but did not change
      the rate of recovery from inactivation. It was found that both reagents reacted
      with the same groups of the channel protein and that those are most likely
      sulfhydryl groups. These groups seemed not to be involved in the gating charge
      movement. Hg2+ ions can immobilize some part of the gating charge thereby
      resulting in strong changes of the steady-state inactivation.

PMID- 1382600
TI  - Inhibitors of the plasma membrane redox system of Zea mays L. roots. The vitamin
      K antagonists dicumarol and warfarin.
AB  - The action of the 4-hydroxycoumarins dicumarol and warfarin, antagonists of
      probable vitamin K type components of the plasma membrane electron-transport
      system, on plasma membrane redox activity of intact maize roots was compared.
      Both effectors inhibited electron transfer to extracellular hexacyanoferrate III.
      While the effect of the strongly lipophilic dicumarol on the electron-transport
      system was irreversible by rinsing, the inhibition caused by the hydrophilic
      warfarin could be reverted completely by exchange of the incubation medium. We
      take these results as possible evidence for the integration of dicumarol into the
      plasma membrane. The action of warfarin may be confined to enzymic sites freely
      accessible from the aqueous apoplasmic solution.

PMID- 1382601
TI  - The mode of action of Vibrio cholerae cytolysin. The influences on both
      erythrocytes and planar lipid bilayers.
AB  - The interaction with erythrocytes of cholera cytolysin (CC) obtained from a non
      01 Vibrio cholerae strain results in the osmotic rupture of target cells upon
      formation by CC of the waterfilled pores in their membranes. The aggregation of
      several toxin monomers is required for the formation of one CC channel with a
      radius of 0.9-1.0 nm. The investigations using planar bilayer lipid membranes
      suggest that the CC-induced pore is an interprotein anion selective channel
      carrying a fixed positive charge. The role of the charge was supported by the
      influence of pH on the selectivity, single conductance and voltage gating of the
      CC channels. The ability of the CC to modify both model and natural membranes has
      a maximum at pH 6.0-7.0. It was found that CC channels insert into the membrane
      asymmetrically. The effect of proteolytic treatment of the channel by papain also
      indicates that the two entrances of the channel protrude from the plane of the
      membrane into the solution for different distances. It is proposed that the
      biological effects of the non-01 V. cholera cytolysin are based on its channel
      forming activity.

PMID- 1382602
TI  - A channel model with fluctuating barrier structures.
AB  - Following the theory 'Fluctuations of barrier structure in ionic channels'
      (Lauger, P., Stephan, W. and Frehland, E. (1980) Biochim. Biophys. Acta 602, 167
      180), we constructed a model of a channels with several conformational states.
      The origin of these conformational states and the source for the transitions from
      one to the other are given explicitly for the presented model. In this work the
      effect of multiple conformational states on the ion transport process is
      analyzed. We considered a channel protein with two main barriers and one binding
      site. The site is surrounded by dipolar groups. The dipole moment of these groups
      can be reoriented by thermal activity and also by electrical interaction with the
      transported ions. Differently polarized states generate different activation
      energy barriers for the ions. The set of conformational states of the channel is
      constituted by all the possible polarized states of the binding site. Using the
      rate-theory analysis of ion transport (Glasstone, S., Laider, K.J. and Eyring, H.
      (1941) The theory of rate processes, McGraw-Hill, New York), the possible
      coupling between ion flux and the channel conformational transitions has been
      incorporated into the model by considering the dependence of the rate constants
      on the heights of the energy barriers. The resulting multistate kinetic equations
      have been solved numerically. It was shown that the simple saturation
      characteristic of the flux-concentration curve was obtained. For certain values
      of the model parameters, the channel shows a strongly different conductance for
      anions compared to cations. In fact, the model contains an interesting mechanism
      that exhibits selectivity with respect to the charge of the ions.

PMID- 1382603
TI  - Mapping of the epitope on lipoprotein lipase recognized by a monoclonal antibody
      (5D2) which inhibits lipase activity.
AB  - A monoclonal antibody, 5D2, which inhibits human lipoprotein lipase (hLPL)
      activity has been widely used for assessment of LPL immunoreactive mass in the
      clinical evaluation of patients [1] and for analysis of structure-function
      relationships of LPL [2,3]. We have mapped the epitope on LPL, recognized by the
      5D2 antibody, within residues 396-405. Ala400 is the critical amino acid residue
      conferring epitope specificity. This knowledge confirms that the C-terminal
      domain of LPL plays a critical role in LPL activity and also provides important
      information for studies exploring the structure-function relationship of LPL
      using this antibody.

PMID- 1382604
TI  - Downregulation of hepatic albumin mRNA in response to induced
      hypercholesterolemia in rabbits.
AB  - Albumin gene expression was studied in rabbits fed on a cholesterol-rich diet for
      up to 16 weeks. Livers from experimental animals showed extensive lipid
      deposition. Hepatic albumin mRNA abundance decreased along the treatment to very
      low levels after 16 weeks. An 8-fold decrease in the rate of transcription of
      this gene was also detected. This downregulation of albumin gene expression
      cannot be attributed to a general impairment of RNA synthesis, as expression of
      other liver-specific and housekeeping genes did not vary significantly. There was
      a decrease in ascitic fluid albumin levels after 10 weeks, although serum albumin
      levels remained unchanged throughout the treatment. Our results are discussed in
      view of the relationship of albumin levels with hypercholesterolemia.

PMID- 1382605
TI  - Sequence and expression of human protein kinase C-epsilon.
AB  - Two human homologues of protein kinase C-epsilon (E1 and E2) were isolated from
      two distinct cDNA libraries. Sequence comparisons to PKC-epsilon cDNAs from
      several species indicated that each of these human epsilon clones contained
      cloning artifacts. Thus, a composite PKC-epsilon (E3) clone was derived from
      clones E1 and E2. Human PKC-epsilon (E3) has an overall sequence identity of 90
      92% at the nucleotide level compared to the previously characterized mouse, rat
      and rabbit clones. At the amino acid level, the deduced human epsilon sequence
      shows a 98-99% identity with the mouse, rat and rabbit sequences. Expression of
      the human PKC-epsilon clone in Sf9 cells confirmed that the recombinant protein
      displayed protein kinase C activity and phorbol ester binding activity. The
      recombinant protein was also recognized by two distinct epsilon-specific
      polyclonal antibodies.

PMID- 1382607
TI  - Failure of tachykinins including substance P and its fragments to influence
      proteoglycan and protein synthesis in bovine chondrocytes in vitro.
AB  - Adult bovine articular chondrocytes were exposed to substance P, neurokinins A
      and B or substance P fragments, SP1-4, SP1-6 and SP7-11 in vitro. Proteoglycan
      synthesis was assessed by measuring proteoglycans which were released into the
      culture medium or incorporated into the cell layer. The intact tachykinins or
      substance P fragments had no direct effect on proteoglycan synthesis. Nor was
      total protein production affected. Gel chromatography, under dissociative
      conditions, revealed that sulphated proteoglycans detected in the medium or cell
      layer following treatment of chondrocytes with substance P, contained
      proteoglycans of similar molecular weight to those produced by cells exposed only
      to diluent controls. Therefore, we conclude that the acceleration of arthritis by
      substance P does not appear to be mediated through an effect on chondrocyte
      synthetic function.

PMID- 1382606
TI  - Expression of a human chimeric transferrin gene in senescent transgenic mice
      reflects the decrease of transferrin levels in aging humans.
AB  - Transgenic mice provide a means to study human gene expression in vivo throughout
      the aging process. A DNA sequence containing 668 bp of the 5' regulatory region
      of the human transferrin gene was fused to the bacterial reporter gene
      chloramphenicol acetyl transferase (TF-CAT) and introduced into the mouse genome.
      Expression of the human chimeric transferrin gene was similar to the tissue
      patterns of mouse and human transferrin. In aging transgenic mice, expression of
      the human chimeric transferrin gene was found to diminish 40% in livers between
      18 and 26 months of age. Transferrin levels and serum iron levels in aging humans
      also diminish, as observed from measurements of total iron binding capacity and
      percent iron saturation in sera from 701 individuals ranging from 0 to 99 years
      of age. In contrast, in transgenic mice and nontransgenic mice, the mouse
      endogenous plasma transferrin and endogenous Tf mRNA increase significantly
      during aging. Neither the decrease of human TF-CAT nor the increase of mouse
      transferrin during aging appears to be part of a typical inflammatory reaction.
      Although the 5' regions of the human transferrin and mouse transferrin genes are
      homologous, sequence diversities exist which could account for the different
      responses to inflammation and aging observed.

PMID- 1382609
TI  - Pulsed static magnetic field effects on in-vitro pineal indoleamine metabolism.
AB  - In-vitro rat pineal glands stimulated with the beta-adrenergic receptor agonist
      isoproterenol to induce melatonin synthesis and exposed for 1 h to a pulsed 0.4-G
      static magnetic field demonstrated significant inhibition of serotonin-N
      acetyltransferase activity and melatonin content. 2-h exposure to pulsed magnetic
      field also resulted in a significant reduction in isoproterenol-induced serotonin
      N-acetyltransferase activity. These results support the idea that the cultured
      pineal gland can be affected directly by artificially generated weak magnetic
      fields.

PMID- 1382610
TI  - Molecular weight determination and compositional analysis of dextran-protein
      conjugates using low-angle laser light scattering technique combined with high
      performance gel chromatography.
AB  - The low-angle laser light scattering technique combined with high-performance gel
      chromatography was applied for characterization of the dextran-ovalbumin and
      dextran-lysozyme conjugates obtained from the mild heating in dry state, which is
      attracting interest as a way leading to stabilization of proteins and to
      production of proteins with excellent emulsifying or antimicrobial ability
      (Nakamura, S., Kato, A. and Kobayashi, K. (1991) J. Agric. Food Chem. 39, 647
      650). According to the above technique, providing the information about the
      molecular weight distribution and the composition of the conjugates, one or two
      dextran molecules were found to be linked to one molecule of the proteins. In
      addition, each of the conjugates was shown to exist as an oligomeric assembly of
      which formation is promoted by an increase in the salt concentration of buffer.
      The observations suggest that the increase in the hydrophobicity of the protein
      moiety as a result of partial denaturation and the introduction of the
      hydrophilic dextran chain affords the conjugate an amphiphilic property.

PMID- 1382608
TI  - Evidence for the existence of RNA of Ca(2+)-channel alpha 2/delta subunit in
      Xenopus oocytes.
AB  - Ba(2+)-currents (IBa) through voltage-dependent Ca(2+)-channels were studied in
      Xenopus oocytes injected with RNA from several excitable tissues, using the two
      electrode voltage-clamp technique. Previous studies have shown that the
      expression of cardiac Ca(2+)-channels can be suppressed by an hybrid-arrest
      procedure that includes co-injection of the tissue-derived RNA with an
      'antisense' oligonucleotide complementary to a part of RNA coding for the Ca(2+)
      channel alpha 1 subunit. In this study, this method was used to investigate the
      role of the alpha 2/delta subunit. Co-injection of RNA extracted from either
      rabbit heart, rat brain or rat skeletal muscle (SkM) with 'antisense'
      oligonucleotides complementary to the alpha 2/delta subunit RNA did not
      substantially affect the expression of IBa in the oocytes. Using the Northern
      blot hybridization method, it was shown that native oocytes contain large amounts
      of alpha 2/delta subunit RNA of Ca(2+)-channel. It is proposed that te
      oligonucleotide treatment fails to eliminate the alpha 2/delta RNA because of the
      vast excess of endogenous alpha 2/delta RNA. These results impose a limit on the
      use of the hybrid-arrest method.

PMID- 1382611
TI  - Membrane proteins from lymphoblastoid cells showing cross-affinity for alpha
      fetoprotein and albumin. Isolation and characterization.
AB  - AFP or SA immobilized on nitrocellulose membranes (AFP-NC or SA-NC) were used as
      affinity matrices to purify cell membrane proteins with affinity for AFP (AFP-BP)
      and for SA (SA-BP) from membrane-enriched extracts of Raji cells (a B-lymphoma
      cell line), as well as for normal resting and activated peripheral blood
      lymphocytes (PBMC). SDS-PAGE and ligand blotting assays showed that AFP-BP and SA
      BP isolated from Raji cells are probably identical molecules. They consisted of
      two sets of polypeptides of 31 kDa and 18 kDa. The glycoprotein nature of
      isolated 31 kDa and 18 kDa peptides was suggested by positive staining with
      Schiff's reagent, and amino-acid analysis revealed similar amino-acid composition
      for the two glycoproteins. In human PHA-activated PBMC, only the 18 kDa
      polypeptide was identified and isolated as AFP-BP or SA-BP. As in Raji cells,
      this 18 kDa polypeptide, isolated by affinity for AFP or for SA, appeared to be
      the same molecule. Contrary to Raji cells and activated PBMC, no proteins with an
      affinity for AFP or for SA were identified or isolated in resting PBMC. These
      observations strongly suggest that the isolated 31 kDa and 18 kDa glycoproteins
      are probably AFP receptors previously demonstrated in several neoplastic and
      normal cells undergoing growth and/or differentiation; indeed, they were
      identical to albumin-binding proteins described by others.

PMID- 1382612
TI  - Immunochemical study of equine chorionic gonadotropin (eCG/PMSG): antigenic
      determinants on alpha- and beta-subunits.
AB  - In the present study we have established an immunochemical mapping of equine
      Chorionic Gonadotropin (eCG/PMSG) using three monoclonal antibodies (mAbs),
      namely the antibodies ECG01, E10 and D7, raised against the native hormone. These
      antibodies do not bind to reduced, alkylated hormone, suggesting that they
      recognize discontinuous rather than continuous epitopes. We have also assessed
      the reactivity of mAbs towards human CG, and ovine, porcine, equine and bovine LH
      and FSH. The antigenic determinant recognized by ECG01 is localized on the alpha
      subunit of equine gonadotropins and of human CG and LH. The epitopes recognized
      by E10 and D7 mAbs appear to be very similar and are present on the beta-subunit
      of eCG and of LHs from all species tested, except hLH, as well as on porcine and
      equine FSHs. Attempts to specify the amino-acid residues involved in these
      epitopes suggest that ECG01 mAb might preferentially bind to residues around
      position 70 whereas the region around disulfide bridges Cys-88-Cys-90 might be
      involved in the epitopes recognized by D7 and E10 mAbs. Topographical
      relationships of epitopes show that ECG01 mAb never binds to eCG simultaneously
      with either D7 or E10 mAbs. Furthermore, simultaneous binding of D7 and E10 mAbs
      on eCG could not be achieved. Thus, these three epitopes appear to be closely
      located on the surface of eCG. Finally, ECG01 mAb inhibits eCG binding to LH and
      FSH receptors, suggesting that its antigenic site is closely related to hormone
      receptor interaction site(s).

PMID- 1382613
TI  - Characterization of the interaction of yeast enolase with polynucleotides.
AB  - Yeast enolase is inhibited under certain conditions by DNA. The enzyme binds to
      single-stranded DNA-cellulose. Inhibition was used for routine characterization
      of the interaction. The presence of the substrate 2-phospho-D-glycerate reduces
      inhibition and binding. Both yeast enolase isozymes behave similarly. Impure
      yeast enolase was purified by adsorption onto a single-stranded DNA-cellulose
      column followed by elution with substrate. Interaction with RNA, double-stranded
      DNA, or degraded DNA results in less inhibition, suggesting that yeast enolase
      preferentially binds single-stranded DNA. However, yeast enolase is not a DNA
      unwinding protein. The enzyme is inhibited by the short synthetic
      oligodeoxynucleotides G6, G8 and G10 but not T8 or T6, suggesting some base
      specificity in the interaction. The interaction is stronger at more acid pH
      values, with an apparent pK of 5.6. The interaction is prevented by 0.3 M KCl,
      suggesting that electrostatic factors are important. Histidine or lysine reverse
      the inhibition at lower concentrations, while phosphate is still more effective.
      Binding of single-stranded DNA to enolase reduces the reaction of protein
      histidyl residues with diethylpyrocarbonate. The inhibition of yeast enolase by
      single-stranded DNA is not total, and suggests the active site is not directly
      involved in the interaction. Binding of substrate may induce a conformational
      change in the enzyme that interferes with DNA binding and vice versa.

PMID- 1382614
TI  - Rapid purification and N-terminal sequencing of a potato tuber cyclic nucleotide
      binding phosphatase.
AB  - A high affinity cyclic nucleotide binding phosphatase was purified to homogeneity
      from potato tubers by a rapid procedure involving batchwise elution from
      carboxymethylcellulose and gel filtration. The phosphatase has a molecular weight
      of 28,000 as estimated from both SDS-PAGE and gel filtration. The phosphatase
      binds to Con A-agarose and is eluted by 0.5 M alpha-methylglucoside. The
      phosphatase catalyses the hydrolysis of nucleoside monophosphates, p
      nitrophenylphosphate and O-phospho-L-tyrosine, but not of O-phospho-L-serine or O
      phospho-L-threonine. N-terminal sequencing of the phosphatase has revealed
      significant homology with two similar-size soybean leaf and stem storage
      glycoproteins.

PMID- 1382615
TI  - Heat and autoclave resistance of cell-spreading activity of vitronectin.
AB  - We have investigated the heat- and autoclave-resistant properties of the cell
      spreading activity of vitronectin, a cell-spreading glycoprotein in animal blood
      plasma. Vitronectin heated at 100 degrees C for 10 min or autoclaved at 121
      degrees C at 1.2 kg/cm2 for 20 min retained the same cell-spreading activity as
      native vitronectin. In contrast, fibronectin and type-I collagen treated in the
      same way lost their activity almost completely. GRGDSP remarkably inhibited the
      cell-spreading activity of native, heated and autoclaved vitronectins. GRGESP did
      not inhibit the activity of native vitronectin, but, unexpectedly, partially
      inhibited the activity of both heated and autoclaved vitronectins. In SDS
      polyacrylamide gel analysis under reducing conditions, vitronectin heated at 100
      degrees C migrated mainly as a monomer, but autoclaved vitronectin migrated at
      both the top and front of the gel instead of at the position of the monomer. The
      change in molecular size during the heat- and autoclave treatments was partially
      prevented by adding 10 mM dithiothreitol or 2% 2-mercaptoethanol to the protein
      solution.

PMID- 1382616
TI  - The effect of vanadate upon the expression of phenylalanine hydroxylase in
      streptozotocin-diabetic rat liver.
AB  - Induction of diabetes in rats is associated with a significant elevation in the
      phenylalanine hydroxylating capacity of the liver. This phenomenon reflects an
      increase in the abundance of both phenylalanine hydroxylase protein and
      phenylalanine hydroxylase-specific mRNA. These changes can be abolished by
      insulin-dependent control of diabetes. We show here that the control of diabetes
      by oral administration of sodium orthovanadate will also nullify the diabetes
      related alterations in phenylalanine hydroxylase expression. In addition,
      diabetes-induced changes in the extent of phosphorylation of phenylalanine
      hydroxylase are reversed by either insulin or vanadate treatment in vivo. These
      treatments also abolished the diabetes-related, approx. 30-fold, decrease in
      glucagon sensitivity of phenylalanine hydroxylation in isolated liver cells.

PMID- 1382617
TI  - Expression of wild-type and mutant medium-chain acyl-CoA dehydrogenase (MCAD)
      cDNA in eucaryotic cells.
AB  - An effective EBV-based expression system for eucaryotic cells has been developed
      and used for the study of the mitochondrial enzyme medium-chain acyl-CoA
      dehydrogenase (MCAD). 1325 bp of PCR-generated MCAD cDNA, containing the entire
      coding region, was placed between the SV40 early promoter and polyadenylation
      signals in the EBV-based vector. Both wild-type MCAD cDNA and cDNA containing the
      prevalent disease-causing mutation A to G at position 985 of the MCAD cDNA were
      tested. In transfected COS-7 cells, the steady state amount of mutant MCAD
      protein was consistently lower than the amount of wild-type human enzyme. The
      enzyme activity in extracts from cells harbouring the wild-type MCAD cDNA was
      dramatically higher than in the controls (harbouring the vector without the MCAD
      gene) while only a slightly higher activity was measured with the mutant MCAD.
      The mutant MCAD present behaves like wild-type MCAD with respect to solubility,
      subcellular location, mature protein size and tetrameric structure. In immunoblot
      comparisons, the MCAD protein was present in normal fibroblasts, but essentially
      undetectable in patient fibroblasts homozygous for the prevalent mutation. We
      suggest that the MCAD protein carrying this mutation has an impaired ability to
      form correct tetramers, leading to instability and subsequent degradation of the
      enzyme. This finding is discussed in relation to the results from expression of
      human MCAD in Escherichia coli, where preliminary results show that production of
      mutant MCAD leads to the formation of aggregates.

PMID- 1382618
TI  - In vivo antitumor activity of a panel of four monoclonal antibody-vinca alkaloid
      immunoconjugates which bind to three distinct epitopes of carcinoembryonic
      antigen.
AB  - A panel of four murine monoclonal antibodies apparently directed against three
      distinct epitopes of carcinoembryonic antigen (CEA) was conjugated via oxidized
      carbohydrate groups to 4-desacetylvinblastine-3-carboxyhydrazide. The resulting
      antibody-vinca conjugates were evaluated for antitumor activity against 2-9-day
      established LS174T human colorectal carcinoma xenografts. The antibodies
      (immunoglobulin G, IgG) employed in this study were 11.285.14 (IgG1), 14.95.55
      (IgG2a), CEM231 (IgG1), ZCE025 (IgG1). Additive immunofluorescence studies
      indicated that CEM231 and ZCE025 recognized the same or a closely related
      epitope(s) on CEA which was distinct from the two epitopes bound by 11.285.14 and
      14.95.55. The in vivo antitumor efficacy studies demonstrated that
      chemoimmunoconjugates prepared from 14.95.55 and ZCE025 were more active than the
      conjugates constructed from the 11.285.14 and CEM231 antibodies. The 14.95.55 and
      ZCE025 immunoconjugates were also more efficacious than free drug or drug
      conjugated to irrelevant murine IgG. The presence of increased carbohydrate
      content on the light chain of ZCE025 may have been responsible for the ability to
      construct ZCE025-vinca conjugates with about twice the drug content
      (approximately 10 mol of vinca/mol of IgG) than was achieved with the other
      antibodies. The highly conjugated form of ZCE025 demonstrated similar efficacy
      but was much less toxic than a ZCE025 conjugate containing 5 mol of vinca/mol of
      IgG. These data indicated that significant differences existed in the ability of
      monoclonal antibodies to target a cytotoxic agent for effective antitumor
      activity even when the immunoconjugates recognized the same antigen or even the
      same or closely related antigen epitope(s). Furthermore, these differences could
      not have been identified without extensive in vivo evaluation for antitumor
      efficacy.

PMID- 1382619
TI  - Activity of ribosomal and tRNA promoters of Bacillus subtilis during sporulation.
AB  - The rrnB operon in Bacillus subtilis includes 21 tRNA genes downstream of the
      ribosomal genes. In addition to the dual promoters upstream of these ribosomal
      genes, a second promoter is found within the tRNA gene region. In this study,
      these two promoter regions were inserted before the lacZ gene and each was
      integrated as a single-copy into the B subtilis chromosome to examine their
      activity during sporulation. Both promoters exhibited similar strength and
      temporal downregulation from vegetative growth through t3 of sporulation. At t3,
      transcription from both promoters was approximately 20% of that in logarithmic
      growth. No obvious function of the second promoter is evident except to boost
      transcription of downstream genes. This function may be important because the
      ribosomal promoters of rrnB are weak relative to other ribosomal promoters. For
      instance, the rrnO promoters were much stronger than the rrnB ribosomal promoters
      and considerably more active at t3. Thus, all ribosomal promoters are not of the
      same strength nor are they transcriptionally downregulated to the same extent
      during sporulation. However, both the rRNA and tRNA promoters in the rrnB operon
      are similar in strength and downregulation.

PMID- 1382620
TI  - The DNA-binding protein HBsu is essential for normal growth and development in
      Bacillus subtilis.
AB  - The hbs operon of Bacillus subtilis comprises a single gene which is localized
      between the spoIVA and mtrA open reading frames, and is situated at 204 degrees
      of the standard map of B subtilis. Expression of hbs is initiated from two
      distinct promoters called P1 and P2. The transcription initiation sites have been
      mapped by primer extension analysis. Sequences upstream from P1 show a -35 and 
      10 region which may be recognized by the vegetative form of RNA polymerase E
      sigma A, whereas sequences upstream from P2 may be recognized by either E sigma C
      or E sigma H minor forms of RNA polymerase. In vegetative cells, hbs is highly
      and equally transcribed from both promoters, P1 and P2. In contrast, in
      sporulating cells, hbs is expressed predominantly from P2. In order to study the
      physiological role of HBsu, we must overcome our failure to interrupt the hbs
      gene within the B subtilis chromosome by using a previously constructed strain,
      BM19, bearing hbs under the control of the IPTG-inducible spac-1 promoter. In
      this strain, growth was found to depend highly on hbs expression. In the absence
      of IPTG, growth was strongly affected culminating in a filamentous cell
      morphology. Although sporulation in IPTG-uninduced BM19 cells was poor, due to
      the limited cell growth, the outgrowth of those spores was delayed by 1 h. In
      contrast, in the presence of IPTG, a condition that induces hbs expression,
      normal outgrowth of spores was observed. The proposed essentiality of the hbs
      gene product for growth and development in B subtilis may be attributed to its
      interaction with replication and transcription as a consequence of its facility
      to wrap DNA and to condense the chromosome into nucleosomelike structures. A
      comparative sequence analysis of HBsu with 18 homologous histonelike proteins of
      diverse origin demonstrated their high conservation throughout evolution.

PMID- 1382621
TI  - Leukocytoclastic vasculitis complicating granulocyte colony-stimulating factor (G
      CSF) induced neutrophil recovery in T gamma-lymphocytosis with severe
      neutropenia.

PMID- 1382622
TI  - [Hemobilia following biliary drainage: percutaneous treatment with arterial
      embolization and biliary fibrinolysis].
AB  - The Authors report a case of haemobilia following the performance of biliary
      drainage. Angiography of the celiac tripod and superior mesenteric artery was
      carried out in order to evidence the lesion and to perform, during the same
      session, embolization of the leaking vessel by means of fibrin sponge particles
      (Spongostan). Subsequent cholangiographic controls demonstrated the presence of
      bile ducts clots then treated by loco-regional infusion of urokinase. On the
      basis of the Authors' personal experience, the combination of loco-regional
      biliary fibrinolytic treatment and embolisation leads to the resolution of the
      cause of hematobilia and of retention jaundice.

PMID- 1382623
TI  - Acute phase reactants and interleukin 6 after total hip replacement. Effects of
      high dose corticosteroids.
AB  - A randomised study was performed to evaluate the association between some
      commonly measured acute phase proteins and interleukin-6 after a standard
      musculoskeletal operation, and to investigate the effect of high doses of
      corticosteroids on these proteins. Eight men and four women with osteoarthrosis
      but who were otherwise healthy and who were each to have an uncemented hip
      prosthesis inserted by the porous coated anatomical technique, were included.
      Patients were randomised to receive methylprednisolone 30 mg/kg body weight 1 1/2
      hours before, and four and 12 hours after, operation (n = 6) and compared to a
      control group (n = 6). Plasma concentrations of C reactive protein, haptoglobin,
      orosomucoid and alpha 1-antitrypsin; serum concentration of albumin; packed cell
      volume; white cell count; and plasma concentration of interleukin-6 were
      measured. The increases in concentrations of acute phase proteins in plasma were
      significantly less in the group given steroids, but this did not have any obvious
      clinical consequences. Increase in the concentration of interleukin-6 preceded
      the increases in acute phase proteins in both groups, reflecting the role of
      interleukin-6 in the regulation of expression of acute phase protein genes in
      hepatic cells. The increase of interleukin-6 in the group receiving steroids was
      less pronounced than that in the control group, indicating that corticosteroids
      inhibit the generation of interleukin-6 in vivo.

PMID- 1382624
TI  - Surgical treatment of acute malignant large bowel obstruction.
AB  - OBJECTIVE: To evaluate the morbidity and mortality in all patients operated on
      urgently for acute large bowel obstruction caused by carcinoma of the colon or
      rectum during a 10 year period. DESIGN: Retrospective study. SETTING: Aalborg
      Hospital, Denmark. SUBJECTS: 156 consecutive patients operated on for obstructing
      primary colorectal cancers. MAIN OUTCOME MEASURES: Operations done, morbidity and
      mortality. RESULTS: 95 patients (61%) had advanced disease (Dukes' stage C or
      "D") and their median age was 73 years (range 38-93). 97 had the obstructing
      lesion resected with a 30 day mortality of 5%. 43 patients underwent primary
      resection and 4 died (9%), and 54 underwent staged resection with one death (2%).
      Complications were common, particularly after staged resections, median hospital
      stay being 19 days after primary, compared with 30 days after staged resection.
      59 patients (38%) had palliative operations with 29 deaths (49%); in 39 the tumor
      was completely unresectable. CONCLUSION: Patients with obstructing primary
      colorectal cancers are a high risk group who are characterised by advanced
      disease and old age. Only prospective trials comparing different operations can
      assess whether it is possible to achieve a reduction in mortality.

PMID- 1382626
TI  - Trypanosoma congolense: the use of 4,6-diamidino-2-phenylindole (DAPI) in the
      akinetoplastic induction sensitivity test.

PMID- 1382625
TI  - Identification of the cross-reacting antigen among Actinobacillus
      pleuropneumoniae strains of serotype 1, 9 and 11 by use of monoclonal antibodies.
AB  - Two monoclonal antibodies (MAbs), lMAb-1 and lMAb-5, against Actinobacillus
      pleuropneumoniae serotype 1 were obtained. In enzyme-linked immunosorbent assay
      inhibition tests with whole cell antigens obtained from serotype 1 to 12 strains
      of A. pleuropneumoniae, lMAb-1 reacted to only a serotype 1, strain 4074. The
      epitope recognized by lMAb-1 was a carbohydrate sensitive to periodate oxidation
      and resided on capsular polysaccharide (CP) of A. pleuropneumoniae serotype 1. On
      the other hand, lMAb-5 reacted with serotype 1, 9 and 11 strains at the same
      degree and its epitope was found to be located on O-polysaccharide of serotype 1,
      9 or 11 lipopolysaccharide (LPS). These results showed that CP was one of the
      serotype-specific antigens of A. pleuropneumoniae, and that O-polysaccharide of
      LPS obtained from serotype 1, 9 or 11 strain was the cross-reacting antigen among
      these strains.

PMID- 1382627
TI  - Use of a modified Transwell culture to quantitate the contribution of non-IL-7
      substances to growth of an IL-7-dependent pre-B cell clone.
AB  - Clone 3 is a mouse pre-B cell line that cannot grow in standard tissue culture
      media but is immortalized by coculture with a bone marrow-derived feeder layer.
      In addition, clone 3 cells can be passaged indefinitely in recombinant
      interleukin-7 (IL-7) in the absence of a feeder layer if maintained at high cell
      density. Using monoclonal antibody to IL-7 and Transwells ligated to dialysis
      membranes, we have examined the relative contributions of IL-7, both endogenous
      and exogenous, and of "non-IL-7" feeder layer factors to growth promotion of
      clone 3 cells. There is synergy between feeder layers and exogenous IL-7 that is
      most marked when the latter is present in suboptimal concentrations. The
      synergizing activity is not neutralized by antibody to IL-7 and appears to be
      freely dialyzable. This "non-IL-7" effect is common to two different feeder
      layers, the one derived from bone marrow (3E) being an IL-7 producer, and the
      other, 3T3 fibroblasts, making no detectable IL-7. These experiments reveal a
      substantial contribution of the dialyzable moiety to the total feeder layer
      effect, and are the first to demonstrate cytokine-dependent low-molecular-weight
      synergy in a coculture. This demonstration is possible because the synergizing
      cofactor(s) can cross a semipermeable membrane whereas the cytokine and its
      neutralizing antibody cannot.

PMID- 1382628
TI  - Serotonergic measures in suicide brain: the concentration of 5-HIAA, HVA, and
      tryptophan in frontal cortex of suicide victims.
AB  - Concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA),
      and tryptophan (TRP) were determined in the frontal cortex of individuals who
      died by suicide, homicide, accident, or the result of physical diseases. Females
      had significantly higher tryptophan concentrations than males. There was a
      significant correlation HVA and the interval between death to refrigeration of
      the body. Mean HVA levels were higher from noon to 5 PM. Suicide and homicide
      victims had significantly higher cortical HVA concentrations than those who died
      of physical disease but not accident victims. This was not accounted for by
      gender, age, postmortem interval from death to refrigeration of the body or to
      autopsy, specimen storage time, or drug effects. The ratio of HVA/5-HIAA was also
      significantly higher in suicides compared with those who died of physical
      disease. No differences in cortical 5-HIAA or tryptophan concentrations between
      the four groups were found. There were no differences in the levels of the three
      substances in violent and nonviolent suicides. There were no significant
      correlations between 5-HIAA, HVA and TRP concentrations in all subjects or any of
      the four subgroups. The implications of these findings for the role of serotonin
      and dopamine in suicide and violence are discussed.

PMID- 1382629
TI  - Relationships among concentrations of steroids, inhibin, insulin-like growth
      factor-1 (IGF-1), and IGF-binding proteins during follicular development in
      weaned sows.
AB  - The experimental objective was to determine how insulin-like growth factor
      binding proteins (IGFBP), as examined by Western ligand blot procedures, related
      to porcine follicular steroidogenesis. Weaned sows were ovariectomized at various
      times after litter removal in three experiments. In experiments 1 and 2, sows
      were ovariectomized at 48-120 h after weaning. In experiment 1, pools of all
      small (1-3 mm), medium (greater than 3-6 mm), or large (greater than 6-9 mm)
      follicles were made for each sow; in experiment 2, fluid was collected
      individually from the 10 largest follicles per ovary. A third experiment was
      conducted to examine changes after an ovulatory dose of hCG, but prior to
      ovulation. In this experiment, sows were treated with eCG at weaning, given hCG
      72 h later, and ovariectomized 0-36 h after the ovulatory dose of hCG. Follicular
      fluid was collected from the 10 largest follicles per sow. In experiments 1 and
      2, IGFBP-3 in follicular fluid remained constant over follicle diameters and
      stage sof development, and IGFBP-2 decreased with advancing follicular
      development as concentrations of estradiol, androstenedione, and progesterone
      increased. In experiment 1, after the presumed LH surge when the concentration of
      all steroids was low, there was a sharp increase in band intensity for IGFBP-2.
      Similarly, estradiol and androstenedione were low in preovulatory sows in
      experiment 2, though progesterone increased and IGFBP-2 decreased with follicle
      diameter. In experiment 3, progesterone remained elevated from 0 to 36 h after
      hCG, even though IGFBP-2 did not increase until after 24 h post-hCG.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1382631
TI  - Expression of c-kit protein during placental development.
AB  - The c-kit proto-oncogene encodes a transmembrane tyrosine kinase receptor and is
      shown to be allelic with the white-spotting locus (W) of the mouse. In order to
      elucidate the role of c-kit protein during placental development, we have
      examined the expression of c-kit protein in the uterus and placenta of mice at
      pre- and post-implantation stages by the avidin-biotin-peroxidase (ABC) method
      using rat anti-mouse c-kit monoclonal antibody. At Days 3 and 5 of pregnancy and
      pseudo-pregnancy, c-kit protein was detected in the glandular epithelium, but
      little expression was observed in the luminal epithelium. At Day 7 of pregnancy,
      expression was detected in the stromal cells around the uterine crypts of the
      mesometrial portion, but not in the vigorously proliferating decidual cells
      around the developing embryo. At Days 9 and 10 of pregnancy, the decidua basalis
      facing invading trophoblasts gradually expressed c-kit protein. In the mature
      placenta, c-kit protein was detected in the labyrinthine and decidual layers, but
      in neither the giant trophoblastic nor the spongiotrophoblastic layer. By
      Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), c
      kit mRNA was detected at the stages of periimplantation and placental
      development. These results suggested that the c-kit protein might be involved in
      the proliferation and differentiation of placenta.

PMID- 1382630
TI  - Uterine uptake of alpha 2-macroglobulin and alpha 1-proteinase inhibitor from the
      blood during early implantation in the mouse.
AB  - The objective of this study was to investigate the uterine uptake of plasma alpha
      1-proteinase inhibitor (53,000 Da) and alpha 2-macroglobulin (725,000 Da) from
      the blood during implantation in the mouse using isotopic methods. The uterine
      uptake of albumin (67,000 Da) and immunoglobulin G (150,000 Da) were also
      measured for comparison. Rates of uptake were assessed from permeability-surface
      area products estimated from the rate at which the tissue volume of distribution
      approaches its steady-state value. The permeability-surface area product
      estimates at implantation sites were 13.3 and 54.8 ml/100 g.h for alpha 2
      macroglobulin and alpha 1-proteinase inhibitor, respectively. Given the
      circulating levels of these proteins in mice, these results demonstrate that
      considerable amounts of plasma proteinase inhibitors are extravasated into the
      interstitium in the vicinity of the implanting blastocyst. The permeability
      surface area products of all the proteins studied, except immunoglobulin G, were
      greater at implantation compared to non-implantation sites, confirming greater
      vascular permeability to plasma proteins at implantation sites compared to non
      implantation sites. Estimates of the permeability-surface area products of the
      studied proteins showed that the uterine vasculature was generally more permeable
      to proteins with a small than with a large molecular size. Nevertheless, the
      ratio of the permeability-surface area product between implantation and non
      implantation sites for the proteins ranged from 1.1 to 2.9 with no obvious
      relationship to molecular size.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382633
TI  - [Exocrine pancreas involvement in chronic enteropathies in infants and children].
AB  - On a number of 135 cases of chronic enteropathies in patients aged 6 months--15
      years, the trypsin, amilasis and lipasis levels in duodenal aspirate were
      investigated. In a high number, the decrease of pancreatic enzymes activity was
      noted and the majority of cases were accompanied by a marked dystrophy (grades II
      or III). Thus, it was not possible to indicate whether the low levels were
      primary or secondary determined.

PMID- 1382632
TI  - Mammary gland differentiation in hypophysectomized, pregnant mice treated with
      corticosterone and thyroxine.
AB  - Swiss Webster mice were hypophysectomized or sham-operated on Day 11 of
      pregnancy. The animals were fitted s.c. with osmotic minipumps containing either
      corticosterone (B) dissolved in Molecusol (Pharmatec, Alachua, FL) or the vehicle
      alone immediately after they were hypophysectomized. Animals in some of the
      experimental groups also received thyroxine (T4) in their drinking water. The
      mice were killed on Day 18 of gestation, and mammary tissue was homogenized and
      extracted for assessment of DNA, RNA, alpha-lactalbumin, and alpha-casein. Serum
      was assayed for placental lactogen-I (PL-I), and placental lactogen-II (PL-II),
      B, and T4. The concentration of PL-II in serum was elevated in the
      hypophysectomized mice, whereas the PL-I concentration did not differ among
      experimental groups. Hypophysectomy decreased both T4 and B concentrations in
      serum, and administration of these hormones restored their serum concentrations
      to normal or, in some cases, somewhat higher than normal levels. Hypophysectomy
      reduced the total RNA content and RNA/DNA ratio of the mammary gland, but
      treatment with B alone or with B and T4 restored RNA levels to those of sham
      operated animals. T4 alone was ineffective in restoring RNA levels. Sham-operated
      animals that received hormonal treatment (B and T4) had the highest levels of RNA
      in the mammary tissue. Hypophysectomized animals had reduced content and
      concentration of alpha-lactalbumin in the mammary gland as compared to all other
      experimental groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382634
TI  - [Cholinergic receptors and anesthesia].
AB  - Postsynaptic chemically controlled ion channels are a possible location for the
      action of anaesthetics. The nicotinic acetylcholine receptor (AcChoR) is a member
      of a superfamily of chemically controlled ion channels, which have a large number
      of structural similarities in common. This receptor provides an excellent model
      for studying the effects of anaesthetics on excitable membrane proteins since it
      is well characterised and available in large quantities. The AcChoR consists of
      five subunits that surround a central ion channel. Anaesthetics can inhibit the
      function of the AcChoR by several different mechanisms: 1. By directly blocking
      the ion channel, 2. by an allosteric inhibition of the ion channel, 3. by
      changing the properties of the cell membrane surrounding the receptor. In high
      concentrations, anaesthetics stabilize the receptor in a desensitized state.
      Investigation of the mode of action of anaesthetics on the AcChoR provides
      important information as to the mechanisms of anaesthesia.

PMID- 1382635
TI  - [Molecular and cellular actions of inhalation anesthetics].
AB  - The cellular and molecular basis of inhalational anaesthesia is still unknown.
      Recent biochemical, neurophysiological and pharmacological interest has focussed
      on membrane proteins in the neuron, the smallest functional entity in the brain.
      In this review, the effects on ion transport and ion channels potentially
      relevant to anaesthesia are analysed with reference to the most extensively
      investigated volatile anaesthetics ether, chloroform, halothane, methoxyflurane,
      isoflurane, and enflurane. Synaptic transmission proved a major target of all the
      volatile substances tested so far. Their inhibitory effect seems to be due to an
      alteration in the Ca(2+)-dependent stimulus-secretion coupling within the
      presynaptic nerve endings. In contrast, the phosphatidylinositol pathway proved
      relatively insensitive. In the postsynaptic membrane, receptor-operated ion
      channels, K+ and Cl- channels are considered possible targets for anaesthetic
      vapours. Likewise, guanine nucleotide-binding proteins, so-called G proteins, are
      promising candidates for future research. So far, only limited data exist on the
      effects of anaesthetics on non-neuronal cellular components of the CNS, e.g.
      glial cells. In view of the rapidly increasing number of potential target
      mechanisms, the future challenge of biologically oriented anaesthesia research
      will be to puzzle out those mechanisms most relevant to the still mysterious
      state of anaesthesia.

PMID- 1382636
TI  - Developmentally appropriate psychosocial care for children affected by parental
      chemical dependence.

PMID- 1382637
TI  - Cell growth on immobilized cell-growth factor. II. Adhesion and growth of
      fibroblast cells on poly(methyl methacrylate) membrane immobilized with proteins
      of various kinds.
AB  - The surface of poly(methyl methacrylate) membrane was partially hydrolysed and
      the carboxyl groups produced were coupled with various protein molecules with
      water-soluble carbodiimide. The immobilized proteins were a cell-growth factor
      insulin, cell adhesion factors fibrinogen and fibronectin, and serum proteins
      albumin and gamma-globulin. The insulin-immobilized poly(methyl methacrylate)
      membrane strongly accelerated the growth and slightly accelerated the adhesion of
      fibroblast cells. The immobilized fibronectin and fibrinogen enhanced the cell
      adhesion, and the former also accelerated the cell growth. The immobilized
      albumin and gamma-globulin influenced the adhesion and growth of cells very
      little. It was found that various proteins specifically influence the adhesion
      and growth of cells in an immobilized state.

PMID- 1382638
TI  - Complement activation and adsorption of protein fragments by functionalized
      polymer surfaces in human serum.
AB  - The interactions between blood and polymer surfaces used in extracorporeal
      circulations result in variable activations of the immune system of complement.
      Measuring concentrations of C3a or C5a in supernatant blood or serum after
      contact with the surface has been the most usual way of assessing this
      activation. Most polymer surfaces bearing various chemical groups were found to
      adsorb C3a and sometimes C5a. After taking into account adsorption, a good
      correlation was found between total C3a generated and CH50 units consumed by most
      of the polymer samples tested. Measuring only C3a remaining in the fluid phase
      should not be considered sufficient to conclude that a material surface is not an
      activator of complement.

PMID- 1382639
TI  - Inhibition of endotoxin-mediated activation of endothelial cells by a
      perfluorocarbon emulsion.
AB  - Endothelial cell (EC) activation plays a key role in the inflammatory response by
      promoting the margination of leukocytes in inflamed loci. Augmented leukocyte
      margination to activated EC is mediated by the increased display of leukocyte
      adhesion molecules on EC surface membranes. The biocompatibility of synthetic
      oxygen-transport fluids is intimately linked to EC function, since one of the
      first tissues encountered by such fluids is the vascular endothelium. We
      investigated the effect of one such agent, a phospholipid-based perfluorocarbon
      emulsion containing 90% w/v perflurooctyl bromide (perflubron, PFOB) on EC
      activation. Human umbilical vein EC (HUVEC) were activated by 5 U/ml interleukin
      1 (IL-1), 20 U/ml tumor necrosis factor (TNF), or 50 ng/ml E coli endotoxin (LPS)
      in the presence or absence of up to 20%, w/v perflubron. HUVEC activation was
      monitored by the extent of up-regulation of expression of intercellular adhesion
      molecule-1 (ICAM) and endothelial-leukocyte adhesion molecule-1 (ELAM). Exposure
      of HUVEC to perflubron did not alter the up-regulation of ICAM or ELAM in
      response to IL-1 or TNF (n = 20). However, at 10% perflubron ICAM up-regulation
      in response to LPS was inhibited by 95 +/- 6% (n = 9; p less than .05). ELAM
      expression was similarly affected. The concentration of perflubron required to
      diminish LPS-induced up-regulation by 50% was 6.0 +/- 0.6% (n = 3). The
      inhibitory effect of 10% perflubron was overcome by greater than 1 ug/ml LPS (n =
      3) and the inhibitory effect was attenuated by adding perflubron to the cultures
      after LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382640
TI  - Hemoglobin linked to polyanionic polymers as potential red blood cell
      substitutes.
AB  - A variety of chemical modifications of hemoglobin (Hb) have been proposed in
      order to transform it into cell-free oxygen carriers. These modifications are
      intended to increase the plasmatic half-life of the protein and to lower its
      affinity for oxygen. We have designed and prepared derivatives of dextran and
      polyoxyethylene functionalized so that, after their covalent fixation onto Hb,
      they can act as permanent effectors and thus lower the oxygen affinity of the
      protein while decreasing its renal excretion. The main characteristic of these
      functionalized polymers is that they possess a relatively high density of anionic
      groups. Benzene hexacarboxylate (BHC) and tetracarboxylate (BTC) linked to water
      soluble polymers such as polyoxyethylene or dextran, yielded polymeric
      derivatives which, even after reaction with oxyHb, gave rise to conjugates with a
      lower oxygen affinity than the native protein. We showed on a conjugate obtained
      by the fixation of a BHC-monosubstituted polyoxyethylene onto oxyHb, that the low
      oxygen affinity was due to the preferential binding of the polymer-linked BHC to
      the beta-terminal valine residues. In the reaction of dextran-linked benzene
      tetracarboxylate (dex-BTC) with oxyHb, a lot of parameters had to be optimized in
      order to obtain conjugates well fitted to the purpose of blood substitute. Thus
      the polymer content in BTC and the amounts of reagents used for the reaction
      determined the oxygen-binding properties, the molecular weights and the
      biochemical characteristics of the conjugates, as well as the viscosity and
      oncotic pressure of the solutions. This optimization resulted in products which
      are now studied in-vivo.

PMID- 1382641
TI  - A potential blood substitute from carboxylic dextran and oxyhemoglobin. I.
      Preparation, purification and characterization.
AB  - Human adult hemoglobin (Hb) from peripheral venous blood was covalently linked,
      under its oxygenated form, to a dextran polymeric effector to yield conjugates
      with low oxygen affinity. The polymeric effector was synthesized by directly
      coupling benzene tetracarboxylic anhydride to dextran (MW approximately 10,000)
      under mild conditions. The reaction parameters were chosen so that the resulting
      polymeric derivative was only very little cross-linked and possessed benzene
      tricarboxylate site concentrations lesser than 1 site for 10 glucose units, as it
      was found that for higher concentrations the polymer exhibited anticlotting
      properties. The reaction between oxyHb and the polymer (dex-BTC) was carried out
      in water in the presence of a water-soluble carbodiimide (EDCI). By optimization
      of the reaction conditions, a dextran-Hb conjugate with a P50 of 21 torr (37
      degrees C, 50mM Bis-tris buffer pH 7.4, 0.14M NaCl, 40 mM glucose) and a
      potential O2 release of 0.30 ml/g Hb between oxygen partial pressures of 100 and
      40 torr, was obtained. The viscosity and oncotic pressure of a solution
      containing about 6% of conjugated Hb were respectively 1.8 cSt (37 degrees C) and
      28 torr (25 degrees C). This solution could be stored frozen at -20 degrees C for
      a long time, without modification of its properties.

PMID- 1382642
TI  - Effect of dextran benzene polycarboxylates on the functional properties of human
      hemoglobin.
AB  - The present study deals with the fixation of benzene polycarboxylates such as
      benzene hexacarboxylate (BHC) or benzene tetracarboxylate (BTC) onto dextran,
      with the aim of obtaining polyanionic polymers capable of decreasing the oxygen
      affinity of Hb by interacting with its phosphate binding site. The synthesis was
      carried out according to several reaction schemes. The polyanionic polymers
      presented the strongest effector properties, when the polyanionic molecule (BHC
      or BTC) were directly fixed onto the hydroxyl functions of dextran in the
      presence of a carbodiimide or by means of the benzene tetracarboxylic anhydride.
      The introduction of a spacer arm between the polymer and the polyanionic molecule
      led to the formation of crosslinking between chains of dextran. Among the
      synthesized polymers those which possess effector properties similar to those of
      2,3-diphosphoglycerate (2,3-DPG) were bound onto oxyHb. The resulting covalent
      conjugates exhibited a low oxygen affinity and a molecular size quite fitted to a
      potential use as blood substitutes.

PMID- 1382643
TI  - A potential blood substitute from carboxylic dextran and oxyhemoglobin. II.
      Physicochemical and physiological assessments. Preliminary results on guinea pig.
AB  - The hemoglobin solution covalently linked to dextran benzene tetracarboxylate
      (dex-BTC) described in Part I, offered the following characteristics: [Hb] = 70
      g/l, non modified Hb less than 15%, metHb less than 5%, P50 close to blood value,
      viscosity and oncotic pressure near to physiological values (37 degrees C). It
      was biocompatible, stable in plasma, non hypotensive in rat model, non pyrogenic
      and did not present abnormal toxicity (on mice, according to the french
      Pharmacopea). Nevertheless, on account of the presence of dextran in the
      conjugate and due to the literature, we observed an anaphylactoid reaction in
      rats consecutive to the injections: absence of hypotension but presence of a
      massive oedema resulting from an important increase in the capillary permeability
      with harmful consequences to the vascular retention and survival time. As guinea
      pigs are insensitive to dextran, we are beginning to assess this conjugate
      solution in this animal. The first results are very promising: a lack of
      mortality after large injection, an almost complete vascular retention, a weak
      urinary loss (only non conjugated Hb), and a plasmatic half-disappearance time
      close to 7h. Results from haemorrhagic shocks to a final hematocrit less than
      0.10 l/l and total and isovolemic exchange transfusions seem to prove a real
      oxygen-carrying capacity of this new Hb solution.

PMID- 1382644
TI  - A potential blood substitute from carboxylic dextran and oxyhemoglobin. III.
      Evaluations by perfusion of normal and ischemic guinea-pig heart.
AB  - Hemodynamic parameters of six groups of guinea-pig hearts were studied by the
      working heart technic of Neely. Three groups were respectively perfused with:
      Krebs-Henseleit, purified native hemoglobin 1gm/dl and hemoglobin conjugated to
      dextran benzene tetracarboxylate 1 gm/dl. Three other groups were perfused under
      the same conditions except that after 30 mn of perfusion, 10 mn of total ischemia
      were produced followed by 30 mn of reperfusion with the previous solutions. All
      solutions contained 10 g/l of BSA. Hearts perfused with Hb solutions without
      ischemia or after ischemia show better parameters than with Krebs-Henseleit.
      These observations suggest that contrary to previously published results,
      purified Hb and more, dextran-BTC-Hb appear to be perfusable and are less
      deleterious for heart than saline without hemoglobin.

PMID- 1382645
TI  - Treatment of cerebral ischemia with Dextran-40 or Fluosol DA 20%.
AB  - A cat stroke model was used to evaluate the efficacy of Dextran-40 (DEX) or
      Fluosol-DA 20% (FDA) in the treatment of focal cerebral ischemia. The animals
      were assigned randomly to one of three treatment groups: control, isovolemic
      hemodilution with DEX or isovolemic hemodilution with FDA. The oxidation state of
      cytochrome aa3 was measured in-vivo using near infrared reflectance
      spectrophotometry. The cerebral edema was measured by magnetic resonance imaging
      (MRI). The MRI edema indices for the three groups revealed that the FDA group had
      less edema (p less than 0.05), approaching that of non-stroke controls. The
      relative oxidation state of aa3 for the DEX group declined both during and after
      hemodilution. At the ninth hour post stroke the FDA group was better (aa3 more
      oxidized. p less than 0.025). Changes in blood and plasma components were
      reflective of the extent of hemodilution. Whole blood viscosity analysis revealed
      a difference (p less than 0.05) at the lower shear rates comparing DEX to FDA
      with FDA being higher than DEX. Two animals in each of the groups were allowed to
      awaken at the end of the procedure for functional assessment. These observations
      suggest that hemodilution with FDA following stroke significantly reduces early
      post-ischemic cerebral edema, improves oxidation in the peri-infarct area and
      appears to minimize functional deficits.

PMID- 1382647
TI  - Mechanism of protein folding. IV. Forming and breaking of disulfide bonds in
      bovine pancreatic tripsin inhibitor.
AB  - The folding mechanism of bovine pancreatic tripsin inhibitor (BPTI) is explained
      theoretically on the basis of the island model, where the driving force of
      folding is hydrophobic interaction. For this purpose, we take a look at the
      formation and breaking of disulfide bonds during the folding process of BPTI. The
      intermediate conformations and the native one are successfully obtained, which
      satisfy the so-called "lampshade" geometrical criterion for the formation of the
      disulfide bonds. The folding pathway is consistent with the renaturation
      experiment by Creighton. In addition, an elaborate treatment of side chains of
      amino acid residues by the software programme CHARMm confirms quantitatively the
      formation of disulfide bridges.

PMID- 1382646
TI  - FK 506 and autoimmune disease: perspective and prospects.

PMID- 1382648
TI  - Rat liver metabolism of benzo[b]naphtho[2,1-d]thiophene.
AB  - Thioarenes, sulfur-containing polycyclic aromatic hydrocarbons, have been
      detected in a number of environmental sources. The metabolism of one thioarene,
      benzo[b]naphtho[2,1,d]thiophene ([2,1]BNT), by F344 rat liver 9000g supernatant
      (S-9) was studied. [2,1]BNT which is structurally analogous and has similar
      carcinogenic potency to chrysene, was metabolized to six ethyl acetate
      extractable metabolites when incubated with S-9 from Aroclor 1254-treated F344
      rats. Each metabolite was collected from reverse-phase HPLC, and their identities
      were determined by analysis of MS and NMR data. In order of elution from HPLC
      they are as follows: (1) trans-1,2-dihydroxy-1,2-dihydrobenzo[b]naphtho[2,1
      d]thiophene, (2) benzo[b]naphtho[2,1-d]-thiophene sulfone, (3)
      benzo[b]naphtho[2,1-d]thiophene sulfoxide, (4) trans-3,4-dihydroxy-3,4
      dihydrobenzo[b]naphtho[2,1-d]thiophene, (5) 8- or 9-hydroxybenzo[b]naphtho[2,1
      d]thiophene, and (6) 7-hydroxybenzo[b]naphtho[2,1-d]thiophene. In addition, the
      identities of metabolites 1, 2, 3, and 4 were confirmed by comparison to
      standards. The syntheses of the sulfone and sulfoxide of [2,1]BNT are reported
      here. The syntheses of the dihydrodiols were reported previously. Metabolite 5, a
      hydroxy[2,1]BNT, was the major metabolite formed by liver S-9 from untreated F344
      rats. Microsomal preparations from these rats also produced significant amounts
      of the dihydrodiols, 1 and 4, and the sulfoxide, 3. Microsomes prepared from
      Wistar rats produced dihydrodiols and the sulfone and sulfoxide of [2,1]BNT.
      Therefore, [2,1]BNT is metabolized by both ring oxidation and sulfur oxidation in
      these two strains of rats.

PMID- 1382649
TI  - Spectroscopic study of the interaction between poly-(9-vinyladenine) and single
      or multistrand RNA.
AB  - The interaction between poly(9-vinyladenine) (PVAd) and poly[r(U)] was
      investigated by means of uv, CD, 1H-, and 31P-nmr spectroscopies. The interaction
      was dependent on the molecular weight of PVAd determined by uv and CD
      spectroscopies. Based on imino proton nmr, it was clearly found that PVAd formed
      the complex with poly[r(U)] by complementary hydrogen bonding. The interaction of
      PVAd with double- and triple-stranded helices of RNA was also investigated by uv
      melting behavior and 31P-nmr spectroscopy. The results suggested that PVAd could
      not interact with the double-stranded poly[r(A)].poly[r(U)] but did with the
      triple-stranded RNA.

PMID- 1382650
TI  - Adenocarcinoma-reactive human monoclonal antibody MS2B6 defines an antigen in
      simple glandular epithelium.
AB  - A human monoclonal antibody (MAb), MS2B6, produced from splenocytes isolated from
      a patient with advanced papillary serous cystadenocarcinoma of the ovary, defines
      a unique human tumor-associated antigen. This antigen, EA2B6 (epithelial antigen
      2B6), is expressed in a tissue-restricted manner on cultured and fresh human
      adenocarcinomas and some normal glandular epithelial tissues. EA2B6 is a 38-48 kD
      protein antigen that co-fractionates with the nuclear matrix-intermediate
      filament scaffold of simple glandular epithelial tissues. EA2B6 is a molecule
      with restricted solubility, and in vitro antigen-antibody binding is dependent on
      the antigen being presented on a solid support. To determine if EA2B6 is a
      cytokeratin, competition studies were undertaken with several cytokeratin
      specific murine monoclonal antibodies. None of these antibodies inhibited the
      binding of human MAb MS2B6 to partially purified EA2B6. Less than 1% of HT29
      colon adenocarcinoma cells and fresh ovarian adenocarcinoma ascites cells express
      EA2B6 on their surface. The majority of EA2B6 is intracellular. Because of the
      restricted tissue distribution of this antigen and stability of the antibody, we
      believe MS2B6 is a good candidate for MAb-mediated diagnosis and therapy of human
      adenocarcinomas.

PMID- 1382651
TI  - Rapid toxicological model for use in assessing ocular drugs.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) were applied to corneas either by in
      vitro or in vivo methods. The in vitro method involved excising and mounting
      corneas in a perfusion system at 37 degrees and exposing drug for 2.5 h. The in
      vivo methods represent either topical administration to the rabbit eye or topical
      in vivo infusion using a fixed well which permitted a constant concentration
      (0.05 per cent) to be applied to the eye of anesthetized rabbits for up to 120
      min. An overlay grid procedure using scanning electron microscopy (SEM) showed
      less per cent endothelial damage with in vivo methods than with the in vitro
      method of administration, but per cent damage depended on which section was
      viewed. Damage to the epithelium and endothelium were also assessed by
      quantitative carboxyfluorescein and Janus green staining and uptake procedures,
      respectively, following drug exposure by the in vivo infusion method. Results for
      the epithelium indicated that the more lipophilic NSAIDs damaged the epithelial
      layer to a greater degree than newly synthesized hydrophilic NSAIDs. Damage to
      the epithelium correlated to the surface activity of the NSAIDs. Qualitative
      assessment of epithelial and endothelial toxicity can be performed with SEM and
      transmission electron microscopy (TEM) while vital staining procedures and the
      SEM grid procedure can be used to quantitatively assess corneal toxicity. The
      staining methods, however, possess advantages over SEM and TEM procedures in that
      they are rapid and do not require laborious preparation. As a result of these
      characteristics, the vital staining procedures could be used as part of a
      biopharmaceutical screening technique in evaluating new ophthalmic drugs.

PMID- 1382652
TI  - Decreased protein kinase C activity is associated with programmed cell death
      (apoptosis) in freshly isolated rat hepatocytes.
AB  - Apoptosis of freshly isolated rat hepatocytes was induced by either the omission
      of fetal bovine serum in the culture medium or addition of the protein kinase C
      inhibitors polymyxin B or staurosporine. The time-course of DNA breakdown into
      oligonucleosome-sized fragments and the activity of protein kinase C was
      determined. Hepatocytes were found to be sensitive to bleomycin which induced a
      high degree of DNA breakdown even within 30 min incubation. Both staurosporine
      and polymyxin B induced DNA degradation in hepatocytes after three hours
      incubation, an effect that was partially prevented by phorbol myristate acetate
      (PMA). After eight hours incubation, PMA failed to counteract this action and
      itself produced the apoptosis of rat hepatocytes. The results suggest the
      involvement of protein kinase C in hepatocyte survival.

PMID- 1382653
TI  - Remnant kidney oxygen consumption: hypermetabolism or hyperbole?
AB  - On the basis of observations in surgically created remnant kidneys of rat and
      dog, a novel hypothesis for progressive injury in the setting of reduced renal
      mass has been put forth. Both rat and dog remnant kidneys exhibit significant
      hypertrophy that is accompanied by an increased rate of oxygen consumption (QO2)
      per remaining nephron but not per gram of tissue. This putative "hypermetabolism"
      is seen in the face of progressive scarring of the tubulointerstitial compartment
      of the remnant kidney, and interventions that reduce QO2 in these models have
      been associated with reduced tissue injury in previous studies. The proposed
      pathway by which an increase in QO2 leads to cellular damage is via the
      production of oxygen-reactive species or free radicals. In this article, the
      available data upon which this "hypermetabolism" hypothesis is based are reviewed
      and the constructs within which these data have been analyzed are examined. From
      these considerations, a set of questions not yet answered that may serve to
      direct more fruitful query into this intriguing problem

PMID- 1382654
TI  - Determination of glomerular size-selectivity in the normal rat with Ficoll.
AB  - Diffusion studies in vitro indicate that Ficoll behaves more like an ideal
      spherical molecule than does dextran, suggesting that Ficoll would be a better
      probe of glomerular pore size than the commonly used dextran. To examine the
      differences between these macromolecules in vivo, the fractional clearances of
      tritiated Ficoll and dextran were measured over a wide range of molecular sizes
      (Stokes-Einstein radius, rs, from 19 to 65 A) in normal euvolemic Munich-Wistar
      rats. Whole-kidney and single-nephron hemodynamic conditions were characterized
      through a combination of clearance and micropuncture measurements. The fractional
      clearance, or sieving coefficient (theta), for dextran significantly exceeded
      that of Ficoll at all molecular sizes examined, theta for dextran being
      approximately 10 times that for Ficoll for rs greater than 30 A. Thus, the
      results with Ficoll imply a more size-restrictive barrier than do the results
      with dextran. The values of theta for Ficoll approximated previously reported
      values for uncharged globular proteins. Although theta for Ficoll at rs = 35 A
      was much smaller than the corresponding value for dextran, it was still
      approximately 30 times greater than typical values of the filtrate-to-plasma
      concentration ratio reported for serum albumin (a polyanion) in the rat, in
      agreement with the concept that glomerular charge-selectivity normally plays an
      important role in the prevention of albuminuria. Three membrane-pore models were
      compared in their ability to represent the dextran and Ficoll sieving data. A
      lognormal pore-size distribution in parallel with a nonselective "shunt" pathway
      was found to be more effective than either an isoporous membrane with a shunt or
      a purely lognormal distribution. On the basis of these laboratory results and
      computations, Ficoll may be preferred over dextran in future studies of
      glomerular size-selectivity.

PMID- 1382655
TI  - Relationship between fatty liver, alanine aminotransferase, HBsAg and hepatitis C
      virus.
AB  - A community health survey of 923 residents aged 30 years or more was performed in
      Putai Township of Taiwan. To elucidate the relationships between hepatitis C
      virus (HCV) and surrogate tests for non-A, non-B hepatitis in hyperendemic areas
      of hepatitis B virus (HBV) serum levels of alanine aminotransferase (ALT),
      triglycerides, cholesterol, hepatitis B surface antigen (HBsAg) and antibody to
      HCV (anti-HCV) were examined. Glucose tolerance tests and the history of diabetes
      treatment were used to define the diabetes status. Fatty liver was diagnosed by
      sonography. The prevalence of anti-HCV was 2.6% (95% confidence interval, 1.6
      3.6%). Elevated ALT and fatty liver were significantly associated with anti-HCV
      in univariate analysis. Anti-HCV was not an associated factor for fatty liver
      after adjusting for serum triglycerides and cholesterol, sex, body mass index and
      diabetes status through multiple logistic regression. However elevated ALT was
      still associated with anti-HCV after adjusting for serum triglycerides, sex, body
      mass index, HBsAg and age through multiple linear regression. The anti-HCV
      prevalence was similar between HBsAg-positive and negative subjects. Aggregation
      of HCV infection was found among spouses. It was concluded that elevated ALT and
      intimate contact with HCV carriers might be associated factors for HCV infection,
      and that HBV infection and fatty liver were not related to HCV infection in
      Taiwan.

PMID- 1382657
TI  - Analysis of cost-effectiveness of different strategies for hepatocellular
      carcinoma screening in hepatitis B virus carriers.
AB  - A mathematical model was used to calculate the efficacy of screening to detect
      hepatocellular carcinoma at a resectable stage in hepatitis B virus carriers.
      Data relating to tumour incidence, efficacy of screening tests and tumour growth
      times were obtained from a literature review. Various tests were costed according
      to charges currently prevailing at the authors' institution. The cost per early
      tumour detected is inversely proportional to tumour incidence. It is relatively
      low for populations with high incidences of hepatocellular carcinoma for example,
      male carriers over the age of 30. Both the costs and the proportions of early
      tumour detected increase with increasing frequency of screening. However, the use
      of ultrasonography at 10 monthly intervals or both ultrasonography and alpha
      fetoprotein estimation at yearly intervals will detect 90% of tumours early at a
      cost of S$20,000 (US$11,800) per early tumour detected. The results would be
      significantly altered if tumour growth times were markedly different from those
      reported in the literature.

PMID- 1382656
TI  - Hepatitis C as the cause of chronic non-A, non-B hepatitis: high sensitivity of
      simultaneous measurement of core and non-structural antibodies.
AB  - First generation serologic tests (ELISA-1) for hepatitis C virus infection
      measure antibodies directed against a short non-structural segment of the virus
      (anti-c100-3). A major disadvantage of this test is that it lacks sensitivity in
      the identification of hepatitis C virus among patients at risk of infection.
      Thus, only 70-90% of chronic non-A, non-B cases are ELISA-1 positive. The present
      study set out to determine whether antibodies directed against the core region
      would be a more sensitive indicator of hepatitis C virus infection in patients
      with chronic non-A, non-B hepatitis. Sera were studied from 97 patients with
      raised serum alanine aminotransferase levels for more than 6 months in whom other
      causes of abnormal alanine aminotransferase were excluded. Using ELISA-1, 85 sera
      (87%) were anti-c100-3 positive. Sera were then tested for presence of antibody
      directed against Po, a core peptide of a Japanese strain of hepatitis C virus,
      using an ELISA method. Eighty-eight sera (91%) were anti-Po positive. Among the
      12 anti-c100-3 negative patients, six were anti-Po positive. A second generation
      ELISA for anti-HCV (ELISA-2) incorporates a different antibody to the core region
      (c22-3) in addition to an expanded non-structural region, c200, which consists of
      c100-3 plus c33c. With these tests, all sera but one were positive, including 11
      of 12 ELISA-1 negative and eight of nine anti-Po negative sera.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1382659
TI  - Plasma disappearance of homologous and heterologous pancreatic enzymes in dogs.
AB  - Homologous and heterologous (human) pure pancreatic juice was infused into dogs
      to compare the behaviour of pancreatic enzymes in the circulation. This was
      achieved by estimating the magnitude of elevation and speed of disappearance of
      pancreatic enzymes in plasma. The half-lives of the plasma enzymes did not differ
      significantly between dogs and humans. However the half-lives of other enzymes
      (longest for amylase and shortest for trypsinogen) did differ. The magnitude of
      elevation expressed as a ratio of peak (5 min) to basal level was greatest for
      trypsinogen (28 times) and least for amylase (1.4 times). However, 289% and 410%
      of the initial lipase enzyme activity was recovered 5 min after infusion of dog
      and human pure pancreatic juice, respectively (44% when measured by
      immunoreactive human lipase activity). The excess recovery requires re-evaluation
      of diagnostic value of turbidimetric activity of plasma pancreatic lipase.

PMID- 1382658
TI  - Hypercholesterolaemia in patients with hepatocellular carcinoma.
AB  - Ninety-one (11.4%) subjects with hypercholesterolaemia (serum cholesterol level
      more than 250 mg/dL) of 792 Chinese patients with hepatocellular carcinoma (HCC)
      were studied in Taiwan. All 91 patients had large tumours greater than 7 cm in
      diameter and a tumour volume greater than 50%; 56 (61%) of these patients
      manifested tumour involvement in both lobes of the liver. The HCC patients with
      hypercholesterolaemia had significantly higher mean serum levels of albumin,
      triglyceride and alpha-fetoprotein (AFP) compared with age-sex-tumour volume
      matched HCC patients without hypercholesterolaemia. The associated incidence of
      hypoglycaemia in hypercholesterolaemic HCC patients was significantly higher than
      in HCC patients without hypercholesterolaemia (15/90 vs 4/90; P = 0.01). There
      was no significant difference in the survival analysis between HCC patients with
      and without hypercholesterolaemia. Eight and 11 of hypercholesterolaemic HCC
      patients had their tumours surgically resected and received transcatheter hepatic
      arterial chemoembolization (TAE), respectively. Serum cholesterol levels fell to
      the normal range after treatment and rose to abnormal levels again when tumours
      recurred after surgery or progressively enlarged after TAE. The change in pattern
      of serum cholesterol was parallel to the change in serum AFP. Serum cholesterol
      levels may serve as another marker in identifying tumour recurrence and the
      presence of a viable tumour mass in hypercholesterolaemic HCC patients who have
      received surgical resection or TAE.

PMID- 1382660
TI  - Phospholipase A2-induced changes in AMPA receptor: an autoradiographic study.
AB  - The expression of long-term potentiation and learning of a classical conditioning
      task increase [3H]-AMPA binding in hippocampus. Phospholipase A2 (PLA2) has been
      proposed to underly these changes, as PLA2 treatment of membrane preparations
      increases the affinity of AMPA receptors for agonists. We demonstrate here that
      preincubation of thin (10 microns) frozen rat brain sections with exogenous PLA2
      and calcium at physiological temperature changes the binding properties of AMPA
      receptors. Quantitative autoradiography reveals that PLA2-treatment produces a
      differential increase in [3H]-AMPA binding across brain regions. The same
      treatment also decreases the binding of an antagonist ([3H]-CNQX) throughout the
      brain. We propose that PLA2 treatment results in a modification of the AMPA
      receptors which is regionally specific, probably due to different AMPA receptor
      subunit compositions.

PMID- 1382661
TI  - Effect of NO synthase inhibition on NMDA- and ischaemia-induced hippocampal
      lesions.
AB  - We assessed the effect of NG-Nitro-L-arginine methylester (L-NAME), an inhibitor
      of nitric oxide synthase, on the hippocampal lesions induced either by the focal
      injection of N-methyl-D-aspartate (NMDA) or (s)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (s-AMPA) or by 10 min of severe forebrain ischaemia (4
      vessel occlusion), in the rat. We find that L-NAME, 20 or 40 mg kg-1, selectively
      decreases NMDA-induced CA1 lesions while it has no effect on AMPA toxicity. L
      NAME, 20 mg kg-1, does not decrease hippocampal damage induced by ischaemia.
      These results suggest that NO contributes to NMDA toxicity and support data
      indicating that NMDA receptor antagonists fail to protect against hippocampal CA1
      lesions in the 4-vessel occlusion model.

PMID- 1382662
TI  - Follicular dendritic cells in the alternative antigen transport pathway:
      microenvironment, cellular events, age and retrovirus related alterations.
AB  - Follicular dendritic cells (FDC) are located in lymphoid follicles of secondary
      lymphoid tissues and play a pivotal role in the initiation and maintenance of the
      secondary antibody response. FDC are an integral part of the microenvironment of
      the follicle and function as members of the 'alternative antigen transport
      pathway.' This pathway consisting of the antigen transport cell-FDC-ICCOSOME-B
      cell axis, leads to the formation of germinal centers where antibody-forming cell
      and memory B cell development are initiated through interaction of FDC-retained
      antigen, B cells and T helper cells. Evidence suggests that these interactions
      are down-regulated through antibody feedback, or as needed, reactivated with the
      utilization of FDC-retained antigen for the maintenance of antibody levels. Age-
      and retrovirus-related FDC defects seriously compromise the capacity of this
      pathway to maintain immunity.

PMID- 1382663
TI  - Treatment of diffuse non-Hodgkin's lymphoma with combined chemotherapy using
      methotrexate, adriamycin, cyclophosphamide, vincristine, prednisolone and
      bleomycin (MACOP-B).
AB  - Forty-nine previously untreated adult patients with diffuse non-Hodgkin's
      lymphoma were treated with MACOP-B (methotrexate, adriamycin, cyclophosphamide,
      vincristine, prednisolone and bleomycin) between December 1986 and December 1990.
      Forty patients (82%) achieved a complete response (CR), three (6%) a partial
      response (PR), while four (8%) had either no response or progression of disease,
      one (2%) patient ceased MACOP-B therapy and received other chemotherapy because
      of sustained neutropenia, and one patient (2%) died of sepsis during therapy. The
      factors that adversely affected the CR rate were by stage IV, the presence of B
      symptoms, the presence of a large mass (greater than 5 cm), and low serum total
      protein level. The 4-year survival for all 49 patients was 70% and the 4-year
      disease-free survival (DFS) for the 40 CR patients was 77%. Relapses were higher
      in patients whose initial serum lactic dehydrogenase (LDH) level was higher than
      660 IU/1 (DSF 89% vs. 49%). Toxicity was substantial but acceptable, with
      neutropenia and mucositis proving to be the most frequent severe side-effects.
      These preliminary results confirmed the effectiveness of MACOP-B therapy for
      diffuse non-Hodgkin's lymphoma.

PMID- 1382664
TI  - Exposure of platelet fibrinogen receptors by a monoclonal antibody to the GPIIb
      IIIa complex, PMA4.
AB  - We found that a monoclonal antibody to the glycoprotein (GP) IIb-IIIa complex,
      PMA4, induces fibrinogen binding to platelets, and we examined the mechanism
      involved. Affinity chromatography and crossed immunoelectrophoresis showed that
      PMA4 recognized an epitope on the GPIIb-IIIa complex-specific domain. The binding
      of 125I-fibrinogen to platelets was induced by PMA4 in a concentration-dependent
      manner and was blocked by EDTA, RGDS peptides and an anti-GPIIb-IIIa monoclonal
      antibody, PMA1. Binding of the divalent antibody to the GPIIb-IIIa complex was
      necessary to induce fibrinogen binding and subsequent platelet aggregation, since
      Fab fragments, unlike PMA4 IgG and F(ab')2 fragments, did not induce fibrinogen
      binding or aggregation. The PMA4 IgG induced fibrinogen binding, serotonin
      secretion, and Ca2+ mobilization, whereas F(ab')2 induced fibrinogen binding
      only. In addition, F(ab')2-induced fibrinogen binding was not abolished in the
      presence of aspirin, H-7, a protein kinase C inhibitor, PGE1 or dibutyryl cyclic
      AMP. These results demonstrate that the binding of PMA4 divalent molecules to the
      GPIIb-IIIa complex can expose platelet fibrinogen receptors in the absence of the
      stimulatory effects of intracellular mediators on platelets. Thus, we conclude
      that the fibrinogen receptors on the GPIIb-IIIa complex can be exposed by direct
      action of the antibody on the complex molecules.

PMID- 1382665
TI  - Late postprandial pancreatic secretion periods in conscious dogs. Effect of
      vagotomy.
AB  - It is well established that, in the dog, the exocrine pancreatic secretion in
      response to food intake is a two-phased mechanism with a first phase during 0-4 h
      period and a second one during 8-12 h period. In the present study we have
      investigated the role played by the vagus nerve in the genesis of this late
      pancreatic hypersecretion (second phase) in dogs with truncal vagotomy and
      pyloroplasty. Truncal vagotomy totally suppressed the first phase of the
      pancreatic secretion; it did not abolish the second postprandial phase but it
      increased its latency by delay of 4 hours. In fact, during the 12-18 h period a
      pancreatic hypersecretory response was evidenced after vagotomy which appeared to
      be statistically significant as compared to basal values (P less than 0.001). Our
      results indicate that the vagus nerve does not play a role in the genesis of the
      late hypersecretory second phase.

PMID- 1382666
TI  - Pattern of irregular dorsal root discharge in the spinal cat.
AB  - Pattern of irregular type of dorsal root discharge (DRD) in non-anaesthetized
      spinal cats was inferred from the distribution of its interspike intervals.
      Interspike interval histograms were compiled from antidromic spike potentials of
      irregular DRD which were recorded in the central ends of 33 single dorsal root
      fibres of L7 dorsal root. The majority of histograms was unimodal. The mean
      preferred interval of irregular DRD which indicated the most frequently occurring
      interspike interval was 6.1 +/- 0.5 ms. The shortest and longest intervals were
      3.7 +/- 0.3 ms and 45.9 +/- 4.4 ms, respectively. The coefficient of symmetry of
      the histogram was 0.06, indicating highly unsymmetrical distribution of intervals
      of irregular DRD. Conduction velocity of dorsal root fibres carrying irregular
      antidromic discharge amounted to 52.3 +/- 5.3 m/s (n = 23). There were no
      significant correlations between three analysed interspike intervals and
      conduction velocity. The results are discussed in view of the hypothesis of the
      modulating effect of antidromic discharge on the afferent inflow. Comparison of
      preferred interspike interval of irregular DRD with the existing data on the rate
      of orthodromic activity in afferent nerve fibres suggests that irregular
      antidromic discharge on many occasions is able to block othodromic impulses by
      collision.

PMID- 1382667
TI  - In vitro effects of divalent metal ions and metabolic modulators on purified
      glutamine synthetase from brain of teleostean fish.
AB  - The purified brain glutamine synthetase of a teleostean fish, Clarias batrachus
      has been examined under the influence of divalent metal ions activation and in
      vitro studies using different amino acids and metabolic modulators. All
      observations of the enzyme activity are based on transferase reaction at optimum
      temperature and pH. The enzyme exhibits an absolute requirement for Mn2+ (most
      potent) Mg2+ and Co2+. The activity is markedly inhibited by leucine, asparagine,
      isoleucine, carbamyl phosphate, uridine monophosphate and glutamate and activated
      by alpha-ketoglutarate. The significance of these results has been discussed in
      brief with emphasis on its involvement in teleostean physiology and metabolism.

PMID- 1382668
TI  - Effect of food deprivation and refeeding on rat organ temperatures.
AB  - Small thermocouple sensors were surgically implanted in the liver, kidney, hind
      leg muscle, interscapular brown adipose tissue, small and large intestines, dorso
      lumbar internal side of the skin, periovaric adipose tissue and the lower aorta
      of Wistar rats. The aortic temperature was taken as core temperature. The sensors
      allowed continuous long-term monitoring of the temperatures of these organs. A
      period of 18 hours of food deprivation resulted in an overall decrease of mean
      core and organ temperature, brown adipose tissue temperature dropping to values
      lower than those of the aorta in the fed state. Liver, kidney and small intestine
      maintained higher temperatures than the aorta both in fed and starved states.
      Refeeding overshot the core temperature with increases in most organs versus both
      the fed and food-deprived situations. The results are concordant with an active
      role of brown adipose tissue in dietary induced thermogenesis. Three days of food
      deprivation did not alter the basic circadian rhythm of core temperatures in the
      rat kept at 22 degrees C, whereas it did modulate both nightly maximum and
      diurnal minimum temperatures to much lower settings than either in the fed or
      refed situations. The rat adapts to starvation by decreasing core and organ
      temperatures and widening the amplitude of the daily temperature cycle.

PMID- 1382669
TI  - [Detailed analysis of human pancreatic secretions collected by retrograde
      catheterization. Parallel or non-parallel excretion of digestive enzymes?].
AB  - Pancreatic juices were collected by selective reverse catherism of the chief
      pancreatic duct in two patients, one free from pancreatic disease and the other
      having a pancreas cancer. They were analysed in detail especially in order to get
      information on the mechanism of enzyme excretion. The variations of the digestive
      enzyme activities (amylase, lipase, trypsin, chymotrypsin, carboxypeptidase A and
      B) were not superimposable among them or with the fluctuations of the protein
      concentration in the pancreatic juice samples. These results agree with a non
      parallel enzyme-excretion mechanism by the pancreas. However deep electrophoresis
      analyses of pancreatic juice samples showed that the ratio of each digestive
      enzyme concentration remained almost constant in the same patient. This
      observation disagrees with the above conclusion and suggests that the data
      obtained by using classical methods for estimating digestive enzyme activities
      have to be considered prudently. By another way, two main significant differences
      were reported by analysing the ionic composition of the pancreatic juice samples
      following their origin. The pancreatic juice samples of the patient having a
      pancreas cancer had a lower and more variable Na+ concentration than those coming
      from the patient who was free from pancreas disease. They had a HCO3-
      concentration which was almost constant, contrary to what was observed for the
      pancreatic juice secreted by the other patient.

PMID- 1382670
TI  - On the latency of blood phenoloxidase of painted locust Poeciloceros pictus.
AB  - The blood phenoloxidase of Poeciloceros pictus exists as proenzyme. The amidase
      activity present in the haemocyte is responsible for the activation of haemocyte
      phenoloxidase. There is an amidase inhibitor in the plasma. Plasma phenoloxidase
      could be activated by various fatty acids, biological compounds like
      lipopolysaccharide zymosan and detergents. Electrophoretic studies suggest that
      activation of haemocyte phenoloxidase involves limited proteolysis. It is
      suggested that the natural activator of plasma phenoloxidase may be fatty acid
      and it does not undergo proteolysis during activation. The biological compounds
      like zymosan or LPS are easily recognised by the factor(s) from the membranes of
      haemocytes.

PMID- 1382671
TI  - In the rat, intestinal lymph carries a significant amount of ingested glucose
      into the bloodstream.
AB  - Intestinal lymph flow in rats receiving an oral load of 3 mmoles of glucose was
      determined by measuring the amount of tritiated gavage water entering via the
      portal route [computed differential arterio-venous tritium water concentrations
      multiplied by portal blood flow) and measuring the total amount of tritium
      transferred from the intestinal lumen to the rest of the rat in a given time
      [from the blood tritium specific activity and the water space (795 ml.kg-1) of
      the rat]. The approximate figure obtained (79.8 ml.kg-1.h) was used for the
      evaluation of the amount of glucose (from 14C-labelled glucose in the gavage)
      transfer via intestinal lymph from the label present in the lymph and its flow.
      Lymph glucose concentration (c. 11 mM) and specific radioactivity were higher
      than those of blood. The amount of glucose actually taken up from the intestinal
      lumen was determined measuring the remaining label in the alimentary canal. The
      portal contribution to label distribution was measured as for tritium water
      transfer. Most glucose label passed through in the form of glucose, with much
      smaller proportions as CO2 and even smaller as lactate and other labelled
      compounds. The results suggest that the contribution of lymph circulation to
      dietary glucose incorporation into the bloodstream may be significant, amounting
      to values higher than 10% of the glucose actually incorporated.

PMID- 1382672
TI  - The 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine causes a differential
      incorporation of hexadecanol into neutral ether ester glycerolipids of 2 variant
      cell lines of rat colon carcinoma.
AB  - The 1-O-octadecyl 2-O-methyl-sn-glycerophosphocholine (ET-18-O-CH3), when
      incubated for 24-48h with cells in culture, exerts a highly selective cytotonic
      activity against a variety of tumor cells that is not seen in normal ones. In
      this study, we present data which indicate that this exogenous molecule altered
      the endogenous synthesis of the neutral ether, ester-sn-glycerols, in 2 variant
      cell lines of a rat colon carcinoma. ET-18-O-CH3, at 20 microM in the medium and
      for an incubation of 48h, inhibited the growth rates of the PRO cells which have
      the ability to metastasize and of the REG cells (the regressive cell line), by,
      respectively, 54 and 67%, as measured after [3H] thymidine uptakes. The synthesis
      of the ether, ester-glycerolipids was followed after an incorporation of [3H]
      hexadecanol into the cell lipids. The radiospecific activity of the alcohol in
      the ether, ester-glycerolipids was higher for the PRO cells than for the REG
      cells. ET-18-O-CH3 activated the incorporation of [3H] hexadecanol in the neutral
      ether, ester-sn-glycerols: 1.55 fold in the PRO cells, but 2.15 fold in the REG
      cells. No change was observed in the alkyl (alkenyl) acyl-sn
      glycerophospholipids. Most of the transformed cells have a low etherase activity
      and are known to accumulate the ether, ester-glycerolipids, (neutral and ionic
      structures).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382673
TI  - Cholinergic mechanisms and bronchoconstriction in guinea-pigs.
AB  - Seventy-four guinea-pigs have been actively sensitized against ovalbumin. The
      effects of bilateral cervical vagotomy and of cholinergic efferent blockade on
      the bronchoconstriction induced by inhaled acetylcholine, histamine or antigen
      have been quantified. Animals were curarized then tested during controlled
      ventilation to ensure constant conditions throughout the whole experiment by
      suppressing the post-vagotomy apneusis. Bronchial sensitivity was estimated by
      calculating the bronchoconstrictor dose-threshold provoking respiratory
      asynchronism. Corresponding variation of total lung resistance and dynamic
      compliance were also measured as indices of bronchial reactivity. The data
      obtained in 27 guinea-pigs indicated that the vagi section produced no
      significant effect on the direct bronchial response to histamine (P greater than
      0.5), to acetylcholine (P greater than 0.1) or to antigen (P greater than 0.5).
      In 47 guinea-pigs, atropine at doses 5 and 10 times higher than the acetylcholine
      blocking one did not alter the direct bronchial response to histamine (P greater
      than 0.5). Higher doses induced a progressive decrease in bronchial sensitivity
      to antigen (.05 greater than P greater than .01) which could be related to the
      repetitive administration of the antigen. According to the present results,
      peripheral cholinergic mechanisms play no significant role in guinea-pigs neither
      in histamine nor in anaphylactic bronchoconstriction. Curarization has no
      influence on resting bronchial tone.

PMID- 1382674
TI  - Simultaneous effect of initial weight, initial crowding, temperature and O2
      concentration on the nutritional use of food by rainbow trout (Oncorhynchus
      mykiss).
AB  - The simultaneous effects of initial weight, initial crowding, temperature and O2
      concentration on the following ratios: relative growth rate percent (RGRP), feed
      efficiency (FE), protein efficiency ratio (PER) and protein productive value
      (PPV) were studied in the rainbow trout. Multivariant equations were obtained for
      each of the mentioned indices. The joint effects of these factors were evidenced
      by means of a multiple correlation analysis. The influence of temperature and, to
      a lesser extent, of crowding, and O2 concentration on the nutritional use of food
      by the trout was demonstrated, their fundamental dependence on factors extrinsic
      to the animal being underlined. The non proportional changes in PER and PPV as
      temperature rises revealed that an increasing part of the ingested aminoacids
      were used for synthesis of fat, non for proteins edification.

PMID- 1382675
TI  - Parathyroid hormone-related peptide inhibits oxytocin-induced rat uterine
      contractions in vitro.
AB  - Synthetic human parathyroid hormone-related peptide (hPTHrP)-(1-34) fragment was
      compared with parathyroid hormone (bovine sequence, 1-34; bPTH-(1-34) for
      inhibiting oxytocin or prostaglandin F2 alpha (PGF2 alpha)-induced contractions
      on rat uterus in vitro. bPTH exhibited a potent (ED50 = 7 x 10(-9) M) inhibition
      on oxytocin-induced contractions. Both bPTH-(1-34) and hPTHrP-(1-34) were
      devoided of any significant effect upon PGF2 alpha-induced uterine contractions.
      Human PTHrP also inhibited oxytocin-induced uterine contractions (ED50 = 77 x 10(
      9) M) and this effect, like that of bPTH, was dose dependent. Human PTHrP-(140
      173) fragment had no significant effect on oxytocin-induced uterine contractions.
      The inhibitory effect of hPTHrP-(1-34) disappeared after pretreatment with
      [Tyr]34-bPTH-(7-34)-NH2, a competitive reversible antagonist of bPTH-(1-34). Thus
      PTHrP might be involved in the control of myometrial activity.

PMID- 1382676
TI  - [Tolerance to exertion after sleep reduction and after taking a hypnotic:
      zolpidem].
AB  - The aim of the present study was to investigate the effects of a delayed bedtime
      (3 a.m.), an advanced rising (3 a.m.), a sleep under placebo and under a hypnotic
      compound, i.e. 10 mg of zolpidem (Stilnox) on sleep structure and on the
      adaptations to a subsequent exercise in 8 male athletes. The chronology of these
      nights was randomized and each treatment administered in a double blind fashion.
      During each experimental night, subjects were monitored with conventional
      EEG/EOG/EMG polygraphic recordings. The next day, athletic performance was tested
      using a bicycle ergometer. A codified exercise was performed and consisted to a
      10 min warm up followed by a 30 min steady state cycling corresponding to 75% of
      predetermined VO2 max. Then the work load increased progressively by steps of 10
      W every minute until exhaustion. The recovery lasted 30 min. Heart rate,
      ventilation, VO2, ERO2 were monitored during all exercise and recovery. Plasma
      lactates and catecholamines were also measured at the same time. The data
      concerning sleep recordings showed that both nights with partial sleep
      deprivation resulted in a drop of time spent in slow wave sleep II (decrease of
      55%) and in rapid eye movement sleep (decrease of 45%) while the amount of slow
      wave sleep III and IV were identical to that observed after the reference night.
      The sleep onset latency and the amount of sleep in stage I was reduced only after
      the delayed bedtime. Sleep data under zolpidem did not show any significantly
      difference in the amount of different sleep stages.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382677
TI  - Measurement of rat lung blood flow with labelled microspheres.
AB  - A modification of the usual microsphere injection method is presented which is
      appropriate for rat lung blood flow measurement. The injection of microspheres
      into the abdominal cava vein, together with the sampling of a reference flow from
      the right ventricle, allowed to calculate pulmonary blood flows in the same range
      than the cardiac output. The differences between the two figures (about 30%) are
      attributed to arterio-venous shunts. The tissue distribution of the microspheres
      bypassing the lung capillary beds agree with this interpretation.

PMID- 1382679
TI  - Thiamin uptake by rat isolated enterocytes: relationship between transport and
      phosphorylation.
AB  - The membrane and intracellular steps of thiamin (T) uptake were studied in rat
      isolated enterocytes. The membrane step was investigated by using enterocytes
      deenergized with 25 microM rotenone and a short (30 s) incubation time, while the
      intracellular metabolic step was assessed by using normoenergized (normal) cells
      incubated for a longer (30 min) time. Evaluation of Km, Jmax and KD (apparent
      passive permeability coefficient) values, at 30 s incubation, indicated that
      deenergization slightly reduced both the affinity and the capacity of the
      saturable component of T uptake, as well as the capacity of the non-saturable
      component. At 30 min incubation, deenergization suppressed completely the
      saturable component, without affecting the non-saturable component. Comparison of
      the Km and Jmax values of the saturable components in normoenergized enterocytes
      at 30 s and 30 min indicated that intracellular metabolic phosphorylation is
      probably the event responsible for the active process involved in T uptake.

PMID- 1382678
TI  - Regional amines levels in the rat brain following intra-accumbens cholecystokinin
      and intraperitoneal amphetamine pre-treatment.
AB  - Cholecystokinin octapeptide (CCK8) coexists with dopamine (DA) in a subpopulation
      of mesolimbic DA neurons including the projections to the nucleus accumbens. In
      this structure, CCK8 has been reported to exert agonist-like or antagonist-like
      effects on DA-mediated behaviours and on amphetamine's locomotor-activating
      effects in rodents. These findings raise the possibility that CCK8 plays a role
      in modulating the neurochemical mechanisms underlying the effects of DA and
      amphetamine in the mesolimbic DA system. The purpose of this study was to
      determine regional tissue monoamine levels in the rat brain and their modulation
      following injection of CCK8 in the nucleus accumbens. The same paradigm was used
      to determine the effects of this octapeptide on changes in amine levels induced
      by amphetamine administered intraperitoneally. DA, norepinephrine (NE), serotonin
      (5-HT) and their primary metabolites, dihydroxyphenylacetic acid (DOPAC),
      homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured
      using a reversed-phase ion pair high-pressure liquid chromatography system with
      electrochemical detection (HPLC-ED). Frontal cortex displayed the highest
      DOPAC/DA ratio and the lowest DOPAC/HVA ratio in contrast to the olfactory
      tubercle. The intraperitoneal injection of amphetamine (1 mg/Kg) followed by the
      intra-accumbens administration of 0.15M saline decreased the levels of DOPAC and
      increased DA, 5-HT and 5-HIAA both in nucleus caudatus and nucleus accumbens. The
      DA agonist induced a decrease in the level of NE in olfactory tubercle and
      frontal cortex. The direct administration of CCK8 (300 pmol) into the nucleus
      accumbens decreased the level of DA, DOPAC and 5-HT mainly in olfactory tubercle
      and nucleus accumbens itself.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382680
TI  - Changes in carbohydrate metabolism of Pila globosa in response to crustacean
      hyperglycemic hormone.
AB  - Hyperglycemia was caused in the snail Pila globosa by the injection of the
      hyperglycemic hormones obtained from fresh water crabs (Oziotelphusa senex senex)
      and marine tiger prawns (Penaeus monodon). Tissue glycogen and total
      carbohydrates presented a significant decrease which indicated that the source of
      hyperglycemia was the tissue carbohydrates. The hyperglycemic principles also
      increased the tissue phosphorylase activity and provided evidence for a possible
      action of the crustacean hyperglycemic hormones in non-arthropod species.

PMID- 1382681
TI  - Absorbability of oleic and palmitic acid in young chicks. Effect of yolk sac
      ablation.
AB  - The aims of the present study were: 1) to describe the changes in the absorption
      of free oleic and palmitic acids in young chicks during the first two weeks after
      hatching; 2) to find out if yolk sac ablation induces any change in the
      absorbability of such fatty acids. The study was carried out in normal and yolk
      sac-ablated broiler chicks aged 2, 8 and 13 days. 14C-labelled oleic and palmitic
      acids were given p.o. in suspension. Stools were collected for 48h and the
      recovery of radioactivity was determined and considered as an indicator of the
      extent of absorption. Our results indicate that the absorption of palmitic acid
      decreased with age (p less than 0.05) whereas the absorption of oleic acid
      increased significantly (p less than 0.005). The changes in the absorptive
      capacity for each fatty acid occurred during the first week. The absorption of
      both fatty acids was greater in yolk-sac-ablated chicks (p less than 0.05). The
      relative contents of different fatty acids in yolk lipids was investigated. The
      results clearly indicate that the ratio OA/PA linearly increased from hatching
      until the 4th day. Thus the possibility that yolk sac lipids passing to the
      intestine through the yolk stalk are able to modify the absorptive processes
      cannot be excluded.

PMID- 1382682
TI  - Alkaline phosphatase and ATPases in brush-border membranes of rat jejunum:
      distinct effects of divalent cations and of some inhibitors.
AB  - The effects of divalent cations and of some inhibitors on the activities of
      alkaline phosphatase and ATPase were examined in rat jejunal brush-border
      membranes (BBM) isolated by tha Ca(2+)-(BBMCa) or the Mg(2+)-precipitation method
      (BBMMg). Similar results were found in BBMCa and BBMMg though generally higher in
      BBMCa. Alkaline phosphatase activity was stimulated by 5 mM MgCl2 (30% to 44%),
      but not by 5 mM CaCl2 or 0.1 mM ZnCl2, at pH 9.5 or 7.4. ATPase activity was
      equally stimulated by 5 mM MgCl2 and by 5 mM CaCI2 (about 150%). Alkaline
      phosphatase activity was significantly inhibited by 1 mM vanadate, 5 mM diamox,
      5.0 mM L-leucine and 1 mM theophylline. In contrast, Ca(2+)-ATPase and Mg(2+)
      ATPase activities were not depressed by those alkaline phosphatase inhibitors,
      but were inhibited by 0.1 mM trifluoperazine (more than 70%). 0.1 mM ZnCl2 also
      appeared to be inhibitory to Ca(2+)-ATPase and Mg(2+)-ATPase, but not to alkaline
      phosphatase activity even in the presence of Ca2+ and Mg2+. These results suggest
      that Ca(2+)-ATPase and Mg(2+)-ATPase activities of the rat jejunal BBM are not
      merely manifestations of alkaline phosphatase, but rather belong to (a) distinct
      enzyme(s).

PMID- 1382683
TI  - Identification of three-element windkessel model: comparison of time and
      frequency domain techniques.
AB  - The problem of the parameter identification of the three-element windkessel model
      is studied. Minimization by least-square technique--LSQ--in time domain and
      frequential techniques--FFT--are compared. Continuous pressure and flow curves
      were recorded in the proximal aorta of an open chest dog. Comparison shows very
      high correlations between the parameter estimations obtained by LSQ and FFT
      methods. However, systematic differences appear between the calculated values,
      but do not seem to endanger physiological interpretation of the results.

PMID- 1382684
TI  - [Structure and function of blood platelets].
AB  - Blood platelets are discoid cellular fragments without nucleus originating from
      megakaryocytes. Platelets are able to respond to a great variety of agonists
      which bind to specific receptors localized on the plasma membrane. This process
      takes place when blood vessels are cut. Platelets then change their shape, adhere
      to newly exposed subendothelial tissues, release the content of numerous
      secretory granules and aggregate together. During this process, a great numbers
      of biochemical reactions are triggered such as phospholipases activation,
      synthesis of mediators and protein phosphorylation. These events result from
      increased cytoplasmic free calcium originating through calcium channels from the
      extracellular medium and from internal stores. Involvement of blood platelets in
      cardiovascular diseases may result from an exaggeration of these mechanisms by
      risk factors and are also discussed.

PMID- 1382685
TI  - [Functional expression of calcium channels in reconstitution models].

PMID- 1382686
TI  - [Cellular mechanism of muscle contraction of bronchial smooth muscle].
AB  - Airway smooth muscle is one of the main effector of bronchial reactivity. The
      understanding of the cellular mechanisms involved in the contraction of this
      muscle has advanced in the recent past since isolated cells in culture can now be
      studied. Extracellular messengers (neurotransmitters and mediators) as well as
      their specific membrane receptors have been analyzed in some details. The
      membrane transduction of extracellular messengers brings about the formation (or
      the increase in the concentration) of the intracellular second messenger which,
      in airway smooth muscle, is the cytosolic calcium (Ca2+i) via activation of
      calcium channels which depend on surface membrane potential changes
      (electromechanical coupling) on the one hand and mainly via mechanisms
      independent of surface membrane potential changes-so-called the
      pharmacomechanical coupling--which involves membrane phosphoinositides
      metabolism. Changes in Ca2+i activate contractile proteins leading the muscle to
      shorten and to develop force via several controlled steps such as phosphorylation
      of myosin or changes in the sensitivity to Ca2+ of the contractile elements.
      Experimental techniques that enable to simultaneously study different aspects of
      the cellular response are being developed in airway smooth muscle and are likely
      to provide complementary information about the cellular physiology and
      pathophysiology of this muscle.

PMID- 1382687
TI  - [Release of acetylcholine and its regulation].
AB  - The mechanism of acetylcholine (ACh) release and its regulation is a widely
      studied subject still underdebated. Although the vesicular hypothesis for ACh
      release is at present largely accepted, alternative theories have been proposed.
      ACh release is triggered by calcium influx through specific presynaptic Ca2+
      channels. The modulation of this calcium influx appears as the main mechanism
      through which ACh release is regulated. This can be achieved by direct
      modification of the presynaptic Ca2+ channel opening or indirectly by a change in
      the polarization level of the presynaptic membrane due to the opening or closing
      of other presynaptic channels (usually K+ channels). The increase in the
      intracellular Ca2+ concentration that triggers ACh release is also under the
      control of Ca2+ membrane exchanges and intracellular Ca2+ buffers. ACh synthesis
      that takes place in the cytoplasm of the terminal, can itself be modulated
      leading to changes in the quantity of ACh available for release. All these
      regulatory mechanisms can be initiated by the activation of presynaptic receptors
      to either ACh itself (autoreceptors) or to other transmitters (heteroreceptors).
      Most often, these presynaptic receptors seem to require the transducing role of G
      proteins and the involvement of various second messengers. Some illnesses
      concerning the cholinergic system can be related to a disfunction of one of these
      presynaptic regulatory mechanisms.

PMID- 1382688
TI  - [Structure and secretory functions of the respiratory epithelium].
AB  - Airway secretions actively participate in respiratory epithelium protection.
      Apart from its main participation in transport of inhaled microorganisms and
      particles by mucociliary clearance, respiratory mucus also contributes to other
      protective purposes such as the control of airway humidification. Biochemical
      components found in secretions, such as mucins, lipids, antibacterial agents
      (secretory IgA, lysozyme, lactoferrin), antioxidant and antiprotease components,
      contribute significantly to the airway epithelium defense.

PMID- 1382689
TI  - [Morphogenesis and modifications of the respiratory epithelium].
AB  - The tracheobronchial tree begins to form during the fourth week of development
      through a series of dichotomic divisions of an entoblastic evagination. The
      morphogenesis and maturation of the respiratory tract depend both on the nature
      of the extracellular matrix which facilitates cell migration and on epithelial
      mesenchymal interactions which induce the proliferation and differentiation of
      epithelial cells. The study of the plasticity and the phenotypic modifications of
      secretory cells during both development and inflammatory remodeling of the
      tracheobronchial mucosa suggests an important role for secretory cells during
      ciliogenesis and repair.

PMID- 1382690
TI  - [Symposium on lactate].

PMID- 1382692
TI  - [Effects of intranasally administered substance P in parkinsonian syndrome].
AB  - The effect of intranasal substance P injection on parkinsonian syndrome and the
      generator of pathologically enhanced excitation (GPEE) in caudate nuclei (CN) was
      investigated. MPTP or reserpine administration in old rats induced oligokinesia,
      rigidity and tremor followed by the high amplitude slow and rapid waves in both
      CN. The bilateral intranasal injection of substance P (25 micrograms/kg) resulted
      in an increase in motor activity and almost completely abolished the rigidity and
      tremor. The reduction of extrapyramidal symptoms was considered as a result of
      the inhibition of GPEE in CN. The possibility of substance P entry from nasal
      cavity into the brain was discussed. The changes of the substance P balance in
      nigrostriatal system was suggested to be on of the pathogenetic links of
      parkinsonian syndrome.

PMID- 1382691
TI  - [RNA synthesis and transport in the rat liver under the effects of pesticide
      cotoran (fluometuron)].
AB  - The experiments on the investigation of pesticide cotoran-effect on RNA synthesis
      and transport were carried out. Cotoran was shown to destroy considerably the
      processes of RNA biosynthesis in rat liver, that results in the decrease of RNA
      transport from nuclei into cytoplasm. By special experiments it was established
      that functional activity and the integrity of nuclear membrane (according to the
      alteration in the activity of nuclear membrane enzyme Mg2-dependent ATP-ase) was
      not destroyed.

PMID- 1382693
TI  - [Cellular localization of human secretory beta globulin in normal and tumor
      tissues].
AB  - Distribution of secretory beta-globulin (S beta G) which possesses affinity for
      steroids was investigated immunohistochemically. Tissue specificity of S beta G,
      produced in adult secretory epithelial cells of the seminal vesicles, salivary
      glands, prostate, bronchi and mammary gland was discovered. The protein was not
      detected in fetal and embryonal tissues. S beta G synthesis is abnormal in
      neoplasms: its expression partly preserves in breast cancer cells and increases
      in epithelium of mammary ducts near the focus of malignancy. In lung cancer and
      bronchial glands cells near the focus of neoplastic transformation S beta G
      positive reaction was not observed.

PMID- 1382694
TI  - [Studies of kinin-like properties of a new peptide isolated from bovine brain].
AB  - Kinin-like properties of two new peptides NRP-11 and P7 which have structural
      similarity with neurotensin (NT) and kallidin (K) were investigated. It was found
      that, unlike NT and K, the new peptides possess reduced myotropic and hypotensive
      activity. On the other hand, similarly to NT and K, the new peptides exhibited a
      high histamine-releasing activity in rat peritoneal mast cells. Possible central
      effects are implied for peptide NRP-11 isolated from bovine brain and its
      fragment P7.

PMID- 1382695
TI  - [Study of the possibility to abolish the action of immunosuppressive factors of
      tumor cells].
AB  - We investigated the efficacy of IL-2, LPS, MDP, TRA, ionomycin and contrykal on
      proliferation of lymphocytes treated by tumor cell immunosuppressive factors
      (ISF). IL-2, LPS and/or MDP did not abolish the influence of P815 and B16 ISF on
      Con A or alloantigen-induced lymphocyte proliferation. TPA and in less extent
      ionomycin and combination of the above preparations totally abrogated the
      suppression of Con A-induced lymphocyte proliferation. In inverted experiments
      Con A abrogated ISF-mediated suppression of lymphocyte proliferation induced by
      TPA plus ionomycin.

PMID- 1382696
TI  - [Cultures of islet cells obtained from the fetal bovine pancreas].
AB  - The pancreas from bovine fetuses of 27-35 cm crown-rump length were used as a
      source of islet cell cultures. Pancreatic tissue was treated by collagenase,
      filtered through the metal sieve and incubated in MEM for 24 h. Using this
      method, cultures similar to so-called pseudo-islets were obtained. Aldehyde
      fuchsin staining and electron microscopy revealed a significant number of beta
      cells within the pseudo-islets, the insulin-producing activity of which was
      confirmed by RIA.

PMID- 1382697
TI  - [Effects of mechanical stimulation on vascularization of the wall of major
      arteries].
AB  - In vivo mechanical stretching induced angiogenesis in the t. adventitia of large
      artery. Vasa vasorum penetrate from t. adventitia into t. media with formation of
      vessel sprouting and migration of the endothelial cells.

PMID- 1382698
TI  - Interaction of human bone marrow fibroblasts with megakaryocytes: role of the c
      kit ligand.
AB  - Human kit ligand (KL), also known as stem cell factor (SCF), steel factor, or
      mast cell growth factor, is a recently identified hematopoietic growth factor
      whose receptor is the product of the c-kit proto-oncogene. Alternative splicing
      of the pre-mRNA of KL/SCF results in secreted and membrane-bound forms of the
      protein. We and others have recently shown that the c-kit gene product is
      expressed on human megakaryocytes and that soluble KL/SCF in combination with
      granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), or IL-6
      increased megakaryocyte progenitor colony formation (CFU-MEG) and stimulated
      mature megakaryocytes. Here we show that adhesion of human megakaryocytes to bone
      marrow stromal fibroblasts, which express the membrane-bound form of KL/SCF
      (mKL/SCF), is mediated in part by the interaction between mKL/SCF and the c-kit
      protein. This interaction also results in marrow fibroblast-stimulated
      proliferation but not an increase in ploidy of megakaryocytes; when the two cell
      types were separated by a transoluble membrane, proliferation did not occur.
      Adhesion and proliferation of human megakaryocytes to an immortalized murine
      stromal cell line SI/SI lacking the KL/SCF gene was impaired, whereas
      transfection of SI/SI cells with human mKL/SCF significantly increased both
      adhesion and proliferation. Marrow stromal fibroblast mKL/SCF may serve both as
      an adhesion structure and as a growth-potentiating factor for megakaryocytes in
      the bone marrow.

PMID- 1382699
TI  - Recombinant human interleukin-9 induces protein tyrosine phosphorylation and
      synergizes with steel factor to stimulate proliferation of the human factor
      dependent cell line, M07e.
AB  - Human interleukin-9 (IL-9) was originally identified and cloned based on its
      stimulatory effect on proliferation of human myeloid cell line, M07e. IL-9
      synergized with Steel factor, the ligand for the c-kit product, to stimulate M07e
      cell proliferation. To investigate potential mechanisms for this, IL-9 was
      assessed for effects on protein tyrosine kinase activities in M07e cells by
      immunoblotting with anti-phosphotyrosine monoclonal antibody; results were
      compared with those of Steel factor alone and in combination with IL-9, and those
      of 12-0-tetradecanoyl phorbol-13-acetate (TPA). Recombinant human IL-9 (10 ng/mL)
      rapidly and transiently induced or enhanced at least four tyrosine phosphorylated
      protein bands with molecular weights of 105, 97, 85, and 81 Kd. This tyrosine
      phosphorylation pattern was different from that generated by recombinant murine
      Steel factor or TPA stimulation and the combination of IL-9 and Steel factor did
      not change the IL-9-induced pattern. IL-9-induced tyrosine phosphorylated bands
      were completely blocked by treatment of IL-9 with anti-IL-9 antibody under
      conditions that also neutralized the synergistic effect of IL-9 with Steel factor
      on M07e cell proliferation. Genistein, a tyrosine kinase inhibitor, blocked
      phosphorylation of IL-9 and Steel factor-induced bands. Unlike Steel factor or
      TPA, IL-9 did not appear to stimulate phosphorylation of 42-Kd mitogen-activated
      protein (MAP) kinase or Raf-1, or enhance MAP kinase activity. MAP kinase and Raf
      1 are serine/threonine kinases that are phosphorylated and activated by many
      growth factors and by agonists for protein kinase C. While the combination of IL
      9 plus SLF did not appear to induce phosphorylation of new bands not already seen
      with either IL-9 or SLF alone, or enhance the phosphorylation of those bands seen
      with either cytokine alone, the results suggest that IL-9 activates specific and
      unique signal transduction pathways.

PMID- 1382700
TI  - CD34+ marrow cells, devoid of T and B lymphocytes, reconstitute stable
      lymphopoiesis and myelopoiesis in lethally irradiated allogeneic baboons.
AB  - CD34+ cells devoid of detectable mature and immature T and B lymphocytes,
      expressing the CD2, CD10, and CD20 antigens, were isolated from marrows of three
      pairs of sex-mismatched, mixed lymphocyte culture (MLC) nonreactive, sibling
      baboons. Reciprocal transplants were performed between members of each pair,
      using the sex chromosomes, identified by standard cytogenetic techniques, as
      markers of the transplanted cells. Five animals from these three pairs were
      transplanted with 0.6 to 2.1 x 10(6)/kg of isolated cryopreserved and/or fresh
      isolated cells that were greater than 95% to 97% CD34+. Before transplantation,
      animals were treated with either single (920 or 1,020 cGy) or split (700 cGy x 2)
      dose total body irradiation. All animals engrafted with donor cells, as
      demonstrated by cytogenetic analysis of bone marrow metaphase cells 4 weeks after
      transplantation, with days to white blood cell count (WBC) greater than 500 being
      19 +/- 2, to WBC greater than 1,000 23 +/- 2, to absolute neutrophil count
      greater than 500 24 +/- 3, and to platelets greater than 20,000 30 +/- 7. Three
      animals died of infectious-related complications at 34, 42, and 109 days after
      transplantation with evidence of host and donor cells (mixed chimerism) in
      marrow. Two animals remain alive and healthy more than 545 and 455 days after
      transplantation with stable mixed chimerism in marrow and blood. For these two
      animals, cytogenetic analysis of granulocyte/macrophage and erythroid colonies
      derived from marrow precursors between weeks 25 and 42 posttransplant showed
      evidence of mixed chimerism. Cytogenetic studies of CD2+ T cells and CD20+ B
      cells isolated from blood of these two animals between weeks 21 and 51
      posttransplant showed the presence of mixed chimerism in both lymphocyte
      populations. Thus, isolated allogeneic CD34+ marrow cells devoid of detectable
      mature and immature T and B lymphocytes can engraft and reconstitute stable long
      term myelopoiesis and lymphopoiesis in lethally irradiated baboons. These results
      are consistent with the hypothesis that CD34+ marrow cells contain pluripotent
      hematopoietic stem cells capable of fully reconstituting lymphohematopoiesis in
      the transplanted host.

PMID- 1382701
TI  - Interferon-gamma increases the expression of the gene encoding the beta subunit
      of the granulocyte-macrophage colony-stimulating factor receptor.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) activates a broad range
      of myeloid cells through binding to high-affinity receptors (GM-CSF-R) consisting
      of at least two distinct subunits, GM-CSF-R alpha and GM-CSF-R beta. The genes of
      these GM-CSF-R subunits have been identified recently, but little is known about
      the regulation of their expression. In this study, we investigated the expression
      of the GM-CSF-R subunit genes in normal human monocytes. Out of a panel of
      various cytokines and factors tested, only interferon-gamma (IFN-gamma) affected
      the expression of one of the GM-CSF-R subunit genes by increasing the GM-CSF-R
      beta mRNA expression threefold to sixfold with no effect on GM-CSF-R alpha.
      Maximal effects occurred 2 to 4 hours after stimulation with 500 to 5,000 U/mL
      IFN-gamma. Nuclear run-on assays and mRNA half-life studies showed that IFN-gamma
      modestly enhanced the transcription of the GM-CSF-R beta gene and stabilized the
      GM-CSF-R beta mRNA, with the latter mechanism predominant. Pretreatment of the
      monocytes with cycloheximide did not abrogate the increase of GM-CSF-R beta mRNA
      expression induced by IFN-gamma, indicating that de novo protein synthesis was
      not required for this activity. When monocytes were exposed to IFN-gamma for 6 to
      24 hours, the number of GM-CSF-R per cell was increased 79% as compared with
      controls, whereas the receptor affinity remained unchanged. These data indicate
      that the GM-CSF-R expression in monocytes may be upregulated by IFN-gamma via an
      increased expression of the beta subunit gene, involving both transcriptional and
      post-transcriptional mechanisms.

PMID- 1382702
TI  - Stem cell factor enhances proliferation, but not maturation, of murine
      megakaryocytic progenitors in serum-free culture.
AB  - The effects of recombinant rat stem cell factor (SCF/c-kit ligand) on murine
      megakaryocytopoiesis were studied using partially purified bone marrow cells
      derived from normal and 5-fluorouracil (5-FU)-treated mice in a serum-free
      culture system. SCF alone did not support the formation of megakaryocyte (M) and
      granulocyte-macrophage-megakaryocyte (GMM) colonies. However, the addition of SCF
      to cultures containing interleukin-3 (IL-3) resulted in a significant increase in
      the number of M and GMM colonies formed by bone marrow cells from normal mice,
      whereas IL-6 augmented only M colony growth. The stimulatory effect of SCF was
      approximately three to four times as high as that of IL-6 on the primitive
      progenitors capable of megakaryocytic-lineage expression derived from 5-FU
      treated mice. In addition, SCF, but not IL-6, significantly increased the number
      of constituent cells in the individual M colonies supported by IL-3. On the other
      hand, SCF did not exert any effect on the size and DNA content of megakaryocytes
      in IL-3-dependent M and GMM colonies, whereas IL-6 enhanced the maturation of
      megakaryocytes. These results suggest that SCF stimulates the proliferative
      process in megakaryocytic progenitors and that the main activity of IL-6 is the
      promotion of megakaryocyte maturation.

PMID- 1382703
TI  - Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor
      beta 1 and cancer chemotherapy compounds in myeloid leukemic cells.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) induces cell death in myeloid
      leukemia by apoptosis. In the M1 myeloid leukemia, this induction of apoptosis
      was inhibited by granulocyte colony-stimulating factor (G-CSF) or interleukin-6
      (IL-6) and to a lesser extent by IL-1 alpha. IL-3 and stem cell factor/mast cell
      growth factor (SCF) showed only a marginal effect, and granulocyte-macrophage and
      macrophage CSFs (GM-CSF and M-CSF, respectively) were inactive. The induction of
      apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by
      GM-CSF and IL-3 but not by the other cytokines. In the absence of TGF-beta 1,
      both M1 and 7-M12 leukemic cells were independent of hematopoietic cytokines for
      cell viability and growth. The cytotoxic compounds vincristine, vinblastine,
      adriamycin, cytosine arabinoside, cycloheximide, and sodium azide, some of which
      are used in cancer chemotherapy, induced cell death by apoptosis in both
      leukemias. As with TGF-beta 1, apoptosis induced by these cytotoxic compounds was
      inhibited by GM-CSF (7-M12 leukemia) and by G-CSF or IL-6 (M1 leukemia).
      Cyclosporine A decreased cell multiplication in M1 cells without inducing
      apoptosis, and G-CSF and IL-6 inhibited the cytostatic effect of cyclosporine A.
      It is suggested that the clinical use of cytokines to correct therapy-associated
      myelosuppression should be carefully timed to avoid protection of malignant cells
      from the cytotoxic action of the therapeutic compounds.

PMID- 1382704
TI  - Involvement of tumor necrosis factor (TNF) receptors p55 and p75 in TNF responses
      of acute myeloid leukemia blasts in vitro.
AB  - Tumor necrosis factor (TNF)-alpha and TNF-beta have multiple effects on human
      acute myeloid leukemia (AML) cells in vitro, including (1) synergistic
      stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and upregulation of interleukin-3 (IL-3) and
      GM-CSF receptors; (2) inhibition of granulocyte-CSF (G-CSF)-induced growth and
      rapid downmodulation of G-CSF receptors; and (3) induction of autocrine growth.
      Recently, two distinct TNF receptors (TNF-Rs), TNF-R(p55) and TNF-R(p75), have
      been identified. In this study, we show that both receptor types may be expressed
      by AML blasts. It has been investigated whether the different effects of TNF on
      AML blasts can be explained by differential activation of the distinct TNF-R
      structures. For this purpose, we used the monoclonal antibodies HTR-1 and HTR-9,
      specifically recognizing TNF-R(p55), and UTR-1, specific for TNF-R(p75). TNF
      (alpha and -beta) mediated synergistic activation with IL-3/GM-CSF, upregulation
      of IL-3/GM-CSF receptors, inhibition of G-CSF-induced growth, and rapid
      downmodulation of G-CSF receptors exclusively result from activation of TNF
      R(p55). In certain cases in which TNF-alpha, rather than TNF-beta, induces AML
      growth through an autocrine mechanism, both TNF-R(p55) and (p75) are involved.
      These data indicate that the variety of TNF responses observed in AML can only be
      partially explained by differential activation of the TNF-R(p55) and (p75)
      structures, and that TNF-R(p55) on AML blasts can transduce both positive
      (synergism with IL-3/GM-CSF) and negative regulatory signals (inhibition of G-CSF
      induced proliferation) following TNF activation.

PMID- 1382705
TI  - Acute lymphoblastic leukemia in patients aged 60 years and over: a population
      based study of incidence and outcome.
AB  - Data on all patients aged 60 or older in whom a diagnosis of acute lymphoblastic
      leukemia (ALL) was made in the Northern Health Region of the United Kingdom, over
      a period of 8 1/2 years, were studied to determine the incidence and range of
      biological subtypes, and the outcome of a variety of therapeutic approaches.
      Forty-nine cases were diagnosed (31% of all adult ALL), giving an incidence of
      0.9 per 100,000 age-specific population (ASP). Immunophenotyping was performed in
      41 patients. Eighteen had common, two T-ALL, 10 null, and 7 B-ALL. Four were
      biphenotypic with both lymphoid and myeloid markers. One patient refused
      treatment and four were considered too frail for chemotherapy. Twenty-two were
      treated palliatively. Aggressive "curative" treatment was planned for 22, but
      three died before it started. The actuarial survival for the whole group was 4%.
      The median survival of the palliatively treated group was 1 month, compared with
      3 months for those given aggressive treatment. Only two patients (aged 74 and 67)
      survived more than 2 years in complete remission (CR), both having been treated
      aggressively. We conclude that the prognosis for those over 60 years of age is
      extremely poor, but that for a small number of patients a useful prolongation of
      good quality life may be achieved. Age should not, by itself, be a bar to
      treatment intended to induce remission. Patients and their relatives should be
      made aware of the overall poor prognosis and advised of the therapeutic goals
      when decisions regarding management are being made.

PMID- 1382706
TI  - Regulation of human embryonic globin genes zeta 2 and epsilon in stably
      transformed mouse erythroleukemia cells.
AB  - Previous work has suggested that the promoter regions of the human embryonic zeta
      2 and epsilon globin genes contain negative regulatory regions that could play a
      role in the repression of these genes in postembryonic erythroblasts. We have
      examined this possibility by studying the expression of these genes in mouse
      erythroleukemia cells, an adult erythroid cell line that might be expected to
      contain repressor molecules that would bind to the putative negative regulatory
      regions. When attached to appropriate upstream regulatory elements (alpha HS-40
      and beta HS1,2) both the zeta and epsilon genes were expressed in these cells at
      a low level, but no increase in expression was observed when similar constructs
      lacking the proposed negative regulatory sequences were introduced into these
      cells. These results cast doubt on the possibility that these sequences play a
      major role in the developmental repression of the embryonic globin genes, unless
      they function only in a normal chromosomal organization.

PMID- 1382707
TI  - Similarity of p53 expression by CD34+ cells in chronic myeloid leukemia and
      normal progenitors detected by flow cytometry.

PMID- 1382708
TI  - Nitric oxide modulation of human leukemia cell differentiation and gene
      expression.
AB  - Nitric oxide (NO) functions as an intercellular messenger molecule in such varied
      contexts as neurotransmission, immune regulation, and the control of vascular
      tone. We report that NO, delivered as purified gas or released from the
      pharmacologic NO donors sodium nitroprusside or 6-morpholino-sydnonimine, caused
      monocytic differentiation of cells of the human myeloid leukemia cell line HL-60
      and altered gene expression. The treated cells stopped proliferating, became
      spread and vacuolated, had increased expression of nonspecific esterase and the
      monocyte marker CD14, and displayed increased capacity to produce hydrogen
      peroxide. Furthermore, these treated cells had increased steady-state expression
      of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1 beta (IL-1 beta), but decreased expression of mRNA for the proto
      oncogenes c-myc and c-myb. The increase in TNF-alpha and IL-1 beta mRNA levels
      was due (at least in part) to a new transcription of these specific mRNAs. NO
      elaborated in the bone marrow microenvironment may have a role in normal and
      malignant hematopoietic cell growth and differentiation.

PMID- 1382709
TI  - Dissociation of human cytokine receptor expression and signal transduction.
AB  - We have examined the relationship between granulocyte-macrophage colony
      stimulating factor (GM-CSF) and interleukin-3 (IL-3) receptor expression and
      signal transduction in populations of HL-60 cells differing in proliferative
      capacity to these cytokines. GM-CSF or IL-3 stimulation of HL-60 cells pretreated
      with either dimethyl sulfoxide (DMSO) or retinoic acid results in increases in
      proliferative response as well as both tyrosine and serine phosphorylation. In
      contrast, neither GM-CSF or IL-3 stimulation of parental HL-60 cells (those not
      treated with DMSO or retinoic acid) produced any changes in either proliferation
      or protein phosphorylation. Thus, although parental HL-60 cells expressed both GM
      CSF and IL-3 receptors, treatment with either DMSO or retinoic acid was necessary
      to confer the capacity for signal transduction as assessed by both a biologic and
      biochemical response. Pretreatment of cells with genistein, a protein tyrosine
      kinase inhibitor, resulted in inhibition of GM-CSF-induced protein tyrosine
      phosphorylation as well as proliferation. These data show a strong correlation
      between cytokine-induced increases in protein phosphorylation and subsequent
      biologic responses. Further, this work demonstrates that cytokine receptor
      expression and signal transduction can be disassociated and suggests the
      potential for independent regulation of these two components of signal
      transduction.

PMID- 1382710
TI  - Interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis and
      demonstration of FGF receptor expression in megakaryocytes and megakaryocytic
      like cells.
AB  - We have investigated the interaction of fibroblast growth factor (FGF) with
      megakaryocytopoiesis. Acidic FGF (aFGF) stimulated the proliferation of murine
      megakaryocytes and human erythroleukemia (HEL) cells in a concentration-dependent
      manner. The concentrations of aFGF required to elicit half-maximum and maximum
      effects were similar for HEL and megakaryocytic colony formation. The effect of
      aFGF was comparable to that of basic FGF (bFGF) in both cell types. The effect of
      both FGFs was found to be synergistic with interleukin-3 (IL-3), and was
      abrogated by a monoclonal anti-IL-6 antibody. A specific cell surface receptor
      complex of approximately 120 Kd was detected for FGF by crosslinking experiments
      on HEL cells and total bone marrow (BM) cells. Single-cell autoradiography of
      megakaryocytes in BM smears and BM cultures showed binding sites for 125I-aFGF.
      Northern blot analysis of messenger RNA (mRNA) from total BM and HEL cells showed
      a 4.4-kb mRNA specific for FGF receptors type 1 (flg) and type 2 (bek). This was
      confirmed by polymerase chain reaction, which also showed the presence of FGF
      receptor mRNA in megakaryocytic-like cells, normal megakaryocytes, and platelets.
      Together, these results indicate that FGF is involved in megakaryocytopoiesis and
      suggest that this interaction may be mediated via FGF receptor type 1 and type 2
      located on the megakaryocytic lineage or on accessory cells responsible for the
      release of megakaryocytic growth-promoting activities.

PMID- 1382711
TI  - Enhanced hematopoiesis in vivo and in vitro by splenic stromal cells derived from
      the mouse with recombinant granulocyte colony-stimulating factor.
AB  - Splenic stromal cells (CF-1 cells) were established from a mouse administered
      recombinant human granulocyte colony-stimulating factor (rG-CSF) to clarify the
      mechanism of splenic extramedullary hematopoiesis induced by the factor. The
      cells were negative for alkaline phosphatase, factor VIII-related antigen, mac I,
      and phagocytosis. They were positive for acid phosphatase, collagen type I,
      collagen type III, and fibronectin. CF-1 cells were not converted to adipocytes
      in a confluent culture with 10(-6) mol/L hydrocortisone. [35S]rG-CSF bound to CF
      1 cells specifically in the growth phase but not in the resting phase. The CF-1
      cells had greater colony-stimulating activities than the normal splenic stromal
      cells. When CF-1 cells were added to bone marrow cells in the spleen colony
      forming cells (CFU-S) assay, the number of colonies in the spleen increased
      between 1.4 and 1.8 times the control without these stromal cells. On the other
      hand, the normal splenic stromal cells had no effect on increasing the number of
      CFU-S colonies. Therefore, these data suggest that a factor-dependent
      hematopoietic microenvironment is generated in the spleen by rG-CSF, and the
      stromal cells that have the hematopoietic potency become dominant in splenic
      extramedullary hematopoiesis induced by rG-CSF.

PMID- 1382712
TI  - Erythropoietin-induced tyrosine phosphorylations in a high erythropoietin
      receptor-expressing lymphoid cell line.
AB  - Retroviral gene transfer of the murine erythropoietin receptor (EpR) cDNA into
      the pro-B-cell line, Ba/F3, was used to generate cells expressing high EpR
      levels. One of the resulting clones, Ba/F3 clone C5, contained 5 integrated
      copies of the gene and expressed, at the cell surface, a single affinity class of
      EpRs at 10 to 15 times the level present on spleen cells from phenylhydrazine
      treated mice. Cross-linking studies with clone C5, using 125I-Ep, yielded the
      same two 105- and 88-Kd major species as that seen with typical erythroid cells.
      This was distinct from that obtained with EpR-transfected COS cells or L cells,
      which gave species of 88 and 65 Kd. This suggests that the biologically active
      EpR complex generated in this Ba/F3 cell line may closely resemble that present
      in native Ep-responsive erythroid progenitor cells. Tyrosine phosphorylation
      experiments showed that several proteins in clone C5 cells were rapidly
      phosphorylated on tyrosine residues in response to Ep, one being the EpR itself.
      The proportion of cell surface EpRs tyrosine phosphorylated in response to Ep was
      substantial, reaching a maximum of approximately 10% within 30 minutes of
      incubation at 37 degrees C. A comparison of Ep- and murine interleukin-3 (mIL-3)
      induced tyrosine phosphorylation patterns in clone C5 cells showed that both
      growth factors stimulated the tyrosine phosphorylation of proteins with molecular
      weights of 135, 93, 70, and 55 Kd. This could suggest that the Ep and mIL-3
      receptors are capable of using the same tyrosine kinase in these cells.

PMID- 1382713
TI  - BALB/3T3 fibroblast-conditioned medium attracts cultured mast cells derived from
      W/W but not from mi/mi mutant mice, both of which are deficient in mast cells.
AB  - Proliferation of murine mast cells is induced by both T-cell-derived and
      fibroblast-derived growth factors. Because the most potent T-cell-derived mast
      cell growth factor, interleukin-3, promotes the migration of mast cells, we
      investigated whether fibroblast-derived growth factors had the chemoattractive
      activity as well. Conditioned medium (CM) of BALB/3T3 fibroblasts induced the
      migration of cultured mast cells (CMC) derived from normal (+/+) mice. BALB/3T3
      CM contained the mast cell growth factor (MGF)/stem cell factor (SCF)/kit ligand
      (KL), which is the ligand for the receptor encoded by the W (c-kit) gene. CMC
      derived from the spleen of W/W mice lack the extracellular domain of the W (c
      kit) receptor, and W/W CMC did not proliferate in response to BALB/3T3-CM.
      However, W/W CMC did migrate normally toward BALB/3T3-CM and, moreover, the
      antibody to the extracellular domain of the W (c-kit) receptor did not inhibit
      the chemoattractive activity of +/+ CMC toward BALB/3T3-CM. These results
      indicated that MGF/SCF/KL itself did not represent the major chemoattractive
      activity. On the other hand, BALB/3T3-CM induced neither proliferation nor
      migration of CMC derived from mi/mi mice. Both W/W and mi/mi mice are deficient
      in mast cells, but the present results suggest that the mechanism of the
      abnormality is different between W/W and mi/mi mice.

PMID- 1382714
TI  - Specific growth inhibition of primitive hematopoietic progenitor cells mediated
      through monoclonal antibody binding to major histocompatibility class II
      molecules.
AB  - In a previous study using a canine model, we reported that a certain anti-class
      II monoclonal antibody (MoAb H81.9), which recognizes an epitope formed by the
      alpha and beta subunits of HLA-DR, prevented long-term engraftment of autologous
      marrow cells if administered intravenously during the first 4 days after 9.2 Gy
      of total body irradiation. Another MoAb (B1F6), reactive with only the beta
      subunit of HLA-DR and -DP, had no adverse effect on engraftment, although both
      MoAbs detect antigens on hematopoietic long-term repopulating cells as determined
      from complement-mediated lysis experiments. In the present study, continuous
      exposure of unfractionated human marrow to MoAb H81.9 specifically inhibited the
      growth of primitive progenitor cells that require multiple hematopoietic growth
      factors for proliferation (high proliferative potential colony forming cells [HPP
      CFC] and burst-forming units-erythroid [BFU-e]), but had no effect on more
      mature, single factor responsive (CFU-GM), progenitor cells. In contrast, MoAb
      B1F6 did not impair primitive progenitor cell growth cultured as unfractionated
      marrow. However, when cell dose-response experiments were performed using CD34
      positive cells plated at low cell densities, the marked inhibitory effects of
      MoAb H81.9 on HPP-CFC and BFU-e colony formation were not seen. These findings
      suggest that MoAb H81.9 may not inhibit primitive hematopoietic cells directly,
      but rather indirectly through the action of potent mediators derived from other
      HLA-DR-positive marrow cells.

PMID- 1382715
TI  - Modulation of granulocyte survival and programmed cell death by cytokines and
      bacterial products.
AB  - Mature circulating polymorphonuclear cells (PMN) have the shortest half-life
      among leukocytes and undergo rapid programmed cell death in vitro. In this study,
      we have examined the possibility that inflammatory signals (cytokines and
      bacterial products) can regulate PMN survival. PMN in culture were found to
      rapidly die, with percentages of survival at 24, 48, 72, and 96 hours of 97.3% +/
      1.9%, 36.8% +/- 5.3%, 14.5% +/- 3.1%, and 4.2% +/- 2.9%, respectively (mean +/-
      SE of 20 different donors). PMN incubated with interleukin-1 beta (IL-1 beta),
      tumor necrosis factor, granulocyte-macrophage colony-stimulating factor (CSF),
      granulocyte-CSF, and interferon-gamma (IFN-gamma), but not with prototypic
      chemoattractants (fMLP, recombinant C5a, and IL-8), showed a marked increase in
      survival, with values ranging at 72 hours of incubation from 89.5% +/- 5.8% for
      IL-1 beta to 47.6% +/- 6.4% for IFN-gamma. The calculated half-life was 35 hours
      for untreated and 115 hours for IL-1-treated PMN. PMN activated with
      lipopolysaccharide (LPS) or inactivated streptococci also showed a longer
      survival compared with untreated cells (94.4% +/- 3.2% and 95.5% +/- 2.4%,
      respectively, at 72 hours). PMN surviving in response to LPS or IL-1 beta
      retained the capacity to produce superoxide anion when treated with phorbol
      esters or fMLP. All inducers of PMN survival protect these cells from programmed
      cell death because they reduced cells with morphologic features of apoptosis and
      the fragmentation of DNA in multiples of 180 bp. Thus, certain cytokines and
      bacterial products can prolong PMN survival by interfering with the physiologic
      process of apoptosis. Prolongation of survival may be important for the
      regulation of host resistance and inflammation, and may represent a crucial
      permissive step for certain cytokines and microbial products that activate gene
      expression and function in PMN.

PMID- 1382716
TI  - CD10/NEP is expressed on Thy-1low B220+ murine B-cell progenitors and functions
      to regulate stromal cell-dependent lymphopoiesis.
AB  - To further characterize the function of the common acute lymphoblastic leukemia
      antigen (CALLA; CD10, neutral endopeptidase 24.11, NEP) in early lymphoid
      development, we have identified murine lymphoid progenitors expressing CD10/NEP
      and analyzed the effects of inhibiting the enzyme in in vitro assays of murine
      lymphoid differentiation. CD10/NEP transcripts and enzymatic activity were
      primarily restricted to the subpopulation of murine lymphoid progenitors, termed
      pro-B cells, which were isolated from bone marrow (BM) and modified Whitlock
      Witte cultures and defined by coexpression of B220 and low levels of Thy-1.
      CD10/NEP transcripts and cell surface enzymatic activity were also detected in BM
      stromal cells known to support the development of B-lymphoid progenitors. In
      contrast, Abelson and H-ras transformed pre-B-cell lines were CD10/NEP- as were
      Thy-1-B220+ pre-B cells from BM and modified Whitlock-Witte cultures and Thy
      1lowLin- (B220-Mac-1-GR-1-Ly-2/3-) uncommitted hematopoietic progenitors from BM.
      The expression of CD10/NEP on murine pro-B cells and BM stromal cells suggests a
      role for the enzyme in early B-cell ontogeny. In modified Whitlock-Witte cultures
      in which Thy-1lowLin- progenitors plated on BM stromal cells differentiate into
      Thy-1lowB220+ pro-B and Thy-1-B220+ pre-B cells, the addition of specific
      CD10/NEP inhibitors increased the number of lymphoid colonies at days 5 through 7
      by 34% (P < .001). The results suggest that CD10/NEP participates in the
      regulation of the earliest stages of stromal cell-dependent B lymphopoiesis.

PMID- 1382718
TI  - Interferon-alpha downregulates the abnormal intracytoplasmic free calcium
      concentration of tumor cells in hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a B-cell tumor affecting the preplasma stage of B
      cell differentiation. One important feature of the disease is its exquisite
      sensitivity to interferon-alpha (IFN-alpha) therapy. Because we showed earlier
      that the CD20 molecule is consistently hyperphosphorylated in hairy cells and
      because previous studies showed that CD20 is involved in regulating
      intracytoplasmic free calcium concentrations ([Ca2+]i) in normal B lymphocytes,
      we measured [Ca2+]i in tumor cell samples from patients with HCL and studied the
      effect of IFN-alpha on this parameter. Using the Ca(2+)-sensitive fluorophore
      fura-2, we observed that hairy cells display a slightly but consistently higher
      [Ca2+]i than normal 48-hour-activated B cells or other leukemic cells.
      Furthermore, both in vitro preincubation of cell samples with IFN-alpha and in
      vivo administration of this cytokine reduced the [Ca2+]i in hairy cells. This
      effect was observed together with a decrease in transmembrane Ca2+ influx.
      However, preincubation with IFN-gamma had no effect. The in vivo correlation
      between the diminution of CD20 phosphorylation and [Ca2+]i in tumor cell samples
      from patients at the beginning of IFN-alpha therapy suggests that these two
      parameters are connected.

PMID- 1382717
TI  - Thrombocytosis in patients with tumors producing colony-stimulating factor.
AB  - We investigated the cause of thrombocytosis in 14 patients with tumors producing
      colony-stimulating factor (CSF). Of the 14 patients, 10 had tumors producing
      granulocyte-CSF (G-CSF) and 4 had tumors producing granulocyte-macrophage--CSF
      (GM-CSF). Thrombocytosis of greater than 400 x 10(9)/L was noted in 8 of 10
      patients with G-CSF-producing tumors and all 4 patients with GM-CSF-producing
      tumors. Median peak platelet counts were, respectively, 511 x 10(9)/L (range, 384
      to 694 x 10(9)/L) and 579 x 10(9)/L (range, 526 to 910 x 10(9)/L) in patients
      with tumors producing G-CSF and GM-CSF. In most patients, thrombocytosis declined
      towards the terminal stage. High interleukin-1 (IL-1) and IL-6 levels were found
      in addition to CSFs in the plasma or culture supernatants of tumor cells obtained
      from most patients. In patients with GM-CSF-producing tumors, these specimens had
      megakaryocyte-CSF (Meg-CSF) activity, which was abolished by anti-GM-CSF
      antibody. These specimens also had megakaryocyte potentiating (Meg-Pot) activity
      attributable to both GM-CSF and IL-6. In patients with G-CSF-producing tumors,
      only Meg-Pot activity due to IL-6 was detected. These results indicate that the
      thrombocytosis in GM-CSF-producing tumors was caused by both the Meg-CSF activity
      of GM-CSF and the Meg-Pot activity of IL-6 plus GM-CSF, while that in G-CSF
      producing tumors was due to the Meg-Pot activity of IL-6.

PMID- 1382719
TI  - Genomic hypomethylation in human chronic lymphocytic leukemia.
AB  - DNA samples from patients with chronic lymphocytic (CLL), chronic myelocytic
      (CML), acute myelocytic (AML), and acute lymphocytic leukemia (ALL), as well as
      samples from patients with multiple myeloma (MM) and healthy volunteers, were
      analyzed for their genomic methylation status using Hpa II and Msp I digestions
      followed by a simple gel electrophoresis and ethidium bromide staining. A
      densitometric method was developed to measure more accurately the extent of
      methylation in genomic DNA samples and the results were confirmed by high
      performance liquid chromatography (HPLC) analysis of hydrolyzed DNA. Southern
      analysis with ornithine decarboxylase (ODC) gene probe was also employed, and the
      levels of ODC mRNA were determined with the aid of polymerase chain reaction
      (PCR). The results indicated that a general genomic hypomethylation was present
      in almost all of the samples obtained from patients with B-cell CLL. This
      hypomethylation was most striking among the patients who were freshly diagnosed
      and among untreated chronic patients. CML appeared to be a heterogenous group,
      comprising patients with normal methylation status in addition to patients with
      slight hypomethylation. Patients with ALL, AML, or MM did not show any signs of
      DNA methylation changes in comparison to healthy volunteers. Although all
      analyzed samples from patients with B-CLL showed hypomethylation of ODC
      sequences, little correlation existed between the mRNA levels and the extent of
      hypomethylation of ODC gene.

PMID- 1382720
TI  - Involvement of CD36 on erythrocytes as a rosetting receptor for Plasmodium
      falciparum-infected erythrocytes.
AB  - Plasmodium falciparum-infected erythrocytes (parasitized red blood cells [PRBCs])
      can adhere to uninfected erythrocytes (RBCs) to form rosettes, and adhere to the
      endothelial cell (EC) surface antigen CD36. These adherence phenomena have
      previously been considered quite different. We show that anti-CD36 monoclonal
      antibodies (MoAbs) reverse rosetting of PRBCs from both a culture-adapted line
      (Malayan Camp [MC] strain) and a natural isolate, GAM425. Three MoAbs that block
      adherence of PRBCs to ECs or C32 melanoma cells also reversed rosetting by
      greater than 50% at levels of less than 1 microgram/mL (OKM5, OKM8, and 8A6). Two
      other MoAbs that react with purified CD36 (1D3 and 1B1), but do not react with
      the surface of C32 cells, failed to reverse rosetting. When rosettes were
      disrupted and the RBCs and PRBCs were pretreated separately with antibodies
      before mixing to allow rosette reformation, only pretreatment of RBCs had an
      effect. MoAb 8A6 pretreatment of RBCs blocked rosette reformation, while MoAb 1B1
      pretreatment did not. Rosetting was also reversed by purified human platelet
      CD36. In conjunction with evidence that CD36 is expressed on normal human
      erythrocytes (van Schravendijk et al, Blood 80:2105, 1992), we conclude that this
      CD36 is able to act as a host receptor for rosetting in the MC strain and some
      natural isolates of P falciparum.

PMID- 1382721
TI  - Normal human erythrocytes express CD36, an adhesion molecule of monocytes,
      platelets, and endothelial cells.
AB  - We have recently shown that rosetting of Plasmodium falciparum (MC R+ line)
      infected erythrocytes (parasitized red blood cells [PRBCs]) with uninfected
      erythrocytes (RBCs) is blocked by coating of the RBCs with anti-CD36 monoclonal
      antibodies (MoAbs; Handunnetti et al, Blood 80:2097, 1992). Adult RBCs have
      previously been considered negative for CD36. However, using fluorescence
      activated cell sorter analysis with the anti-CD36 MoAbs 8A6, OKM5, and OKM8,
      which reverse rosetting, we consistently detect CD36 on the majority of normal
      adult RBCs. Absorption of the MoAb solutions with CD36-transfected Chinese
      hamster ovary (CHO-CD36) cells removed the reactivity against both CHO-CD36 cells
      and RBCs, whereas absorption with CHO cells had no effect. By comparison with
      staining for glycophorin A, LFA-3, and CR1, the level of expression of CD36
      appeared to be low. Nevertheless, normal RBCs were capable of adhering to plastic
      coated with anti-CD36 MoAbs. RBCs from one African malaria patient were
      identified as deficient in CD36 and these RBCs did not rosette with the patient's
      own P falciparum PRBCs, even though these PRBCs were capable of rosetting with
      RBCs from a normal donor in a CD36-dependent manner. Therefore, the level of
      expression of CD36 on normal RBCs is sufficient to be important in cell
      adherence, and may have a biologic role in normal individuals as well as in the
      pathology of P falciparum malaria.

PMID- 1382722
TI  - Double NOR is not a good indicator of risk for Down syndrome.
AB  - The silver staining technique was applied to study the nucleolar organizer
      regions (NORs) of 38 parents of children with Down syndrome and 40 parents of
      healthy offspring. Double NOR (dNOR) variants were found in both groups of
      parents. We compared the incidence of dNOR between these two groups. Our results
      indicate that different conclusions can be drawn from the same data depending on
      how the analyses are carried out. It seems to us that dNOR is not a useful marker
      for predicting whether or not its carrier is at a higher risk of having children
      with Down syndrome.

PMID- 1382724
TI  - Cooperative research centre profile cellular growth factors.

PMID- 1382723
TI  - Endocrine therapy for advanced breast cancer: a review.
AB  - More than 45,000 women will die of metastatic breast cancer in the United States
      in 1991. Endocrine therapy remains a major option for treatment of such patients,
      and results in complete plus partial response rates of 30% with a median duration
      of approximately one year. Postmenopausal status, increased age, a prolonged
      disease-free interval, bone and soft tissue metastases, and positive estrogen and
      progesterone receptors are all associated with an increased response to endocrine
      therapy. The use of additive hormonal therapy, specifically antiestrogens,
      progestins, and aromatase inhibitors, have replaced surgical ablative procedures
      in the majority of patients; response rates to antiestrogen therapy, progestin
      therapy, and aromatase inhibitors are similar, but antiestrogens have generally
      been associated with the most favorable therapeutic index. At present, there is
      no convincing evidence that either combinations of endocrine therapies or
      endocrine therapy combined with chemotherapy are associated with an improvement
      in survival for patients with metastatic disease. Future research efforts
      directed at defining the molecular mechanisms of endocrine activity should
      facilitate clinical trials of newer and potentially more effective agents. All
      patients with metastatic breast cancer should be considered for at least one
      trial of endocrine therapy provided their metastatic disease is not rapidly
      progressive or life-threatening.

PMID- 1382726
TI  - Fibronectin and fibrinogen degradation products stimulate PMN-leukocyte and mast
      cell degranulation.
AB  - The ability of various peptides cleaved by plasmin from human fibrinogen and
      fibronectin or fibrinogen- and fibronectin- related synthetic peptides to induce
      histamine release from mast cells and collagenase and elastase from PMN
      leukocytes was examined. Low molecular weight fibrinogen degradation products
      showed dose dependent secretion of collagenase. These peptides (mol. wt. 1.4 kD)
      at the concentration of 10(-5) M released about 47% of collagenase and 13% of
      elastase. Synthetic fibrinopeptides A and B had a similar strong collagenase
      releasing potency and also released histamine from mast cells. Peptides from
      plasmin digestion of fibronectin containing cell attachment site with sequence
      Arg-Gly-Asp-Ser and also synthetic peptide reproducing this amino-acid sequence
      at the concentration of 1000 micrograms/ml released about 50% of collagenase and
      55% of elastase from PMN-leukocytes. Moreover peptides containing cell attachment
      and gelatin binding site induced histamine release from mast cells. The
      association of fibrinogen and fibronectin degradation with activation of mast
      cells may motivate the treatment with antihistaminic drugs of all pathological
      conditions where the intensive protein degradation takes place.

PMID- 1382725
TI  - Synthesis and macromolecular organization of gastrointestinal mucin.
AB  - Mucus glycoproteins (mucins), the principal determinants of mucus protective
      qualities and mucosal defense, are studied extensively to define pathological
      aberrations in the relation to gastrointestinal disease and to develop the mucous
      barrier strengthening agents. Recent work from our laboratory provided evidence
      as to the initial stages of the gastrointestinal mucin synthesis, molecular size
      of the apomucin, its macromolecular organization and interaction with other
      elements of gastrointestinal mucus. Using monoclonal antibodies against apomucin
      (clone 1H7), O-glycosylated with N-acetylgalactosamine apomucin (clone 2B4), and
      that against carboxyl terminal of the apomucin (clone 3G12), the mucin
      synthesizing polysomes were isolated and glycosylated peptides ranging in size
      from 6-60 kDa identified. The in vitro synthesis in the cell-free system also
      afforded 60-64 kDa products recognized by 1H7 and 3G12 antimucin MAbs. The
      obtained results provided evidence that the mucin core consists of 60 kDa peptide
      which at cotranslational stage is O-glycosylated with N-acetylgalactosamine.
      Studies on mucin polymer assembly revealed that mucin preparations prepared by
      equilibrium density gradient centrifugation and Sepharose 2B chromatography
      (Mantle, M., Mantle, D., and Allen, A. (1981) Biochem. J. 195, 277-285) are not
      completely purified and contain DNA and extraneous proteins. The evidence was
      obtained that so called mucin "link protein", 118 kDa glycopeptide, is a N
      glycosylated fragment of fibronectin, whereas the supposedly native undegraded
      mucin isolated by Carlstedt et al. (Biochem. J. (1983) 211, 13-22) was found to
      contain mucin-fibronectin-DNA complexes. The general picture that emerged from
      the studies is that the pure mucin consists of 60 kDa glycosylated peptides only.
      The carboxyl terminal (8-12 kDa fragment) of these peptides is not glycosylated
      (naked) and is responsible for mucin interaction with fibronectin and other
      fibronectin-like extracellular matrix proteins. While the formation of the
      mucosal coat depends on many other factors and extracellular components, our
      findings on mucin structure and interaction with the extracellular matrix
      proteins provide explanation as to the possible mechanism of mucin adherence to
      the epithelial surfaces.

PMID- 1382727
TI  - The continent ileal reservoir--an experimental study.
AB  - This thesis describes new concepts pertaining to the continent ileostomy. The aim
      of the study was twofold: to counter valve desinvagination and to simplify pouch
      construction. In Chapter 1 a survey is given of the history, the present
      situation of the technique and the complications of the continent ileostomy. It
      appears that on the one hand the operation improves the quality of the patient's
      life, but on the other hand the operation gives rise to many complications. The
      number of complications quoted in the literature varies and has been reported to
      be as high as 43%. Most of the time this led to repeat surgery, with equally
      uncertain results. This is the reason why the operation is not very frequently
      performed. Most of the time the complications concern the valve system and to a
      lesser degree the reservoir. In order to obtain a better insight into the origin
      of and possible gain better control over these complications an investigation was
      carried out on laboratory animals. This investigation involved: the complications
      of the valve system, the effect of the suturing method on the function of the
      reservoir and the simplification of the construction of the reservoir. In Chapter
      2 the aim of the investigation was formulated in three questions. 1. Is it
      possible to diminish the chance of complications of the valve system of the
      continent ileostomy? 2. Does the method of suturing influence the function of the
      reservoir? 3. Is it possible to simplify the construction of the reservoir, so
      that the duration of the operation can be shortened? Chapter 3 is the general
      materials and methods section. Chapter 4 is about the research on the valve
      system. Up to now, no method of suturing the valve has consistently produced
      results good enough to make subsequent re-operations unnecessary. In this study
      two types of valve experiments have been carried out. First the feasibility of
      circumventing the problems of the nonpermanent form of the valve was investigated
      combining a short papilla with a 10 centimeter long, anti-peristaltic sutured
      section of the ileum. The assumption was that permanence of the form would be
      more easily obtained in a shorter valve (2 centimeter instead of 5 centimeter).
      After an initial period of continence, incontinence occurred on the average after
      10 months. Autopsy showed that the short papilla had disinvaginated.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1382728
TI  - Acute phase proteins in alcoholics with or without liver injury.
AB  - Acute phase proteins behaviour has been examined in chronic alcoholics to verify
      the hypothesis that chronic alcohol consumption stimulates the hepatic synthesis
      of acute phase proteins. Certain acute phase proteins were studied in two groups
      of alcoholics, one with and one without liver damage, and in a third group of
      healthy volunteers. The results show that the acute phase proteins were similar
      in the two groups of alcoholics, but differed when compared to the control group.
      The authors have concluded from these results, that chronic alcohol consumption
      causes a serum increase of: mucoproteins (p less than 0.001), alpha 1 acid
      glycoprotein (p less than 0.05), haptoglobin (p less than 0.05) and fibrinogen (p
      less than 0.02). Such increases are independent from the existence of liver
      damage.

PMID- 1382729
TI  - Obtaining consent from the family: a horizon for clinical ethics.

PMID- 1382730
TI  - Metallic stents in biliary disease.
AB  - The development of self-expanding metallic endoprostheses which can be implanted
      easily, with minimal trauma, has revolutionized the non-surgical treatment of
      both benign and malignant biliary strictures. The Wallstent (Medinvent SA,
      Lausanne, Switzerland), a pliable, tubular stainless steel mesh, is the metallic
      stent of choice for treatment of malignant strictures and can be implanted in a
      single session resulting in a shortened hospital stay for patients undergoing
      palliation of irresectable biliary tumours. Although follow-up is currently
      rather limited, it appears that the occlusion rate of Wallstents will be lower
      than that of plastic endoprostheses and no cases of stent migration have been
      reported. The Gianturco zigzag stent (Cook Inc., Bloomington, Ind, USA) should
      not be used in malignant strictures because of rapid occlusion due to tumour
      ingrowth through the struts. However, it exerts a strong, continuous, outward
      radial force and is ideally suited for use in the small, but difficult to manage,
      group of patients with benign biliary strictures which recur despite surgery and
      repeated balloon dilations.

PMID- 1382731
TI  - Accurate histochemical definition of argon-laser-induced tissue necrosis.
AB  - We present a histochemical method using the redox dye nitro blue tetrazolium
      chloride (NBTC) for the evaluation of argon-laser-induced tissue damage. By this
      method viable cells are stained blue, devitalized cells not. Our findings suggest
      that the NBTC staining method is more appropriate for the accurate definition of
      the necrosis and cell viability after laser treatment than routine histology.

PMID- 1382732
TI  - [Demonstration of thymidine phosphorylase activity in human healthy, adenomatous
      and cancerous prostate].
AB  - The presence of thymidine phosphorylase in human healthy, adenomatous and
      cancerous prostate was demonstrated. The enzyme was responsible for the cleavage
      and synthesis of thymidine and for the transfer of deoxyribose from one
      deoxyribonucleoside to a pyrimidic base. The enzyme from normal and adenomatous
      prostate was retained on DEAE-Sephadex gel. In PC-3 cells, two enzymes with
      thymidine phosphorylase activity were present, one was retained on the gel, the
      second was excluded from it. Thymidine phosphorylase activity was higher in
      adenomatous and cancerous tissues that in healthy ones. In all tissues, the
      reactions of thymidine synthesis and of deoxyribose transfer were more important
      than that of thymidine cleavage.

PMID- 1382733
TI  - Evaluation of complement in patients with eosinophilic pneumonia.
AB  - Complement evaluation was performed in two patients with active eosinophilic
      pneumonia and in one in remission, to determine the role of complement activation
      in the pathogenesis of this disorder. All three had cough, dyspnea, malaise, and
      blood eosinophilia; two patients also had pyrexia. In all 3 cases the pulmonary
      eosinophilic infiltrates (radiographic findings) and symptoms responded rapidly
      to steroid administration. The two patients with active eosinophilic pneumonia
      showed elevated CR3 but reduced FcrR on the PMN before and during steroid
      administration. In contrast PMN from four patients with bronchial asthma
      exhibited slightly elevated expression of both CR3 and FcrR during their asthma
      attack. It is suggested that clinical symptoms disappear soon after the beginning
      of steroid but changes of complement receptors on PMN may last for longer
      periods. On the basis of the combined results, this study indicates that
      estimation of complement activation may provide a useful indicator for disease
      activity in patients with eosinophilic pneumonia of unknown etiology.

PMID- 1382734
TI  - Leukoencephalopathy induced by tegafur: serial studies of somatosensory evoked
      potentials and cerebrospinal fluid.
AB  - A case of leukoencephalopathy induced by tegafur, an antineoplastic derivative of
      5-FU, is reported. The patient received 600 mg of tegafur p.o. for 16 days before
      excision of rectal cancer. After the operation, gait disturbance and mental
      abnormalities appeared. He became akinetic and mute within a few days following
      readministration of tegafur. Serial studies of brain CT, somatosensory evoked
      potentials (SEP) were made, and myelin basic proteins (MBP) in the cerebrospinal
      fluid were measured. The level of MBP was about twice the normal value and the
      central conduction time (CCT) of SEP was prolonged at admission. The value of MBP
      and CCT improved with recovery from akinetic mutism.

PMID- 1382735
TI  - Silent partners. Patients' views about choice and decision making in a day unit.
AB  - The profile of day case surgery has been gaining prominence in the last decade.
      Improvements in surgical techniques have allowed a greater range and number of
      surgical procedures to be performed on a day case basis. Day case surgery also
      offers considerable efficiency benefits, with lower cost per case than the
      equivalent in patient treatment. Consequently, the number of surgical day cases
      has been increasing rapidly although considerable variation still exists between
      districts. A further advantage of day case surgery arises from its compatibility
      with the consumerism inherent in the health service reforms. The flexibility and
      speed of day case surgery permits a response to consumers' demands for a service
      that meets their needs rather than the hospitals. It offers a reduction in
      waiting times and the choice to avoid the arduous and often traumatic experience
      of being admitted to hospital. Bowling, in a short review of the research
      evidence, suggests that day case surgery generally meets with consistently high
      levels of patient satisfaction. The most welcome aspect of the recent health
      service reform is, perhaps, the emphasis on patients' rights and individual
      choice. Nurses, who are often the closest to the patients, have frequently drawn
      attention to the need for partnership, and an informed and participative
      relationship with the patient. While the Department of Health's genuine
      commitment to patient choice and participation may be little more than skin deep,
      in the case of day case surgery it appears that consumption and the improvements
      in efficiency desired by the government may be compatible with nurses'
      aspirations for greater patient choice.

PMID- 1382736
TI  - Acute toxicity and oxygen consumption in the gills of Procambarus clarkii in
      relation to chlorpyrifos exposure.

PMID- 1382737
TI  - Exposure of a mixer-loader to insecticides applied to corn via a center-pivot
      irrigation system.

PMID- 1382738
TI  - [Integrated traditional and Western medicine treatment of severe viral
      myocarditis].
AB  - 33 patients divided into 2 groups for treatment. Group A (18 cases) early use of
      adrenal cortico-steroid treatment in combination with traditional Chinese
      medicine; group B (15 cases): early use of adrenal cortico-steroid treatment is
      combination with interferon, then compared the therapeutic effects of these 2
      groups. The results showed that, in these 2 groups, the sinus-atrial block,
      atrial ventricular block, ventricular tachycardia, acute pump failure as well as
      the EKG changes were relieved and improved to the same degree. In group A, after
      therapy, the parameters of OKT3 (%) was elevated from 51 +/- 15.22 to 55.23 +/-
      8.53; OKT4(%) was elevated from 30.06 +/- 11.47 to 47.32 +/- 10.87; ratio of
      OKT4/OKT8 was elevated from 1.11 to 1.53; all of their P values were < 0.01. NK
      cell activity was elevated from 8.36 +/- 3.75 to 13.08 +/- 5.77, P value < 0.05.
      In group B, the parameters of OKT3 (%) was elevated from 50.91 +/- 8.12 to 56.75
      +/- 8.29; OKT4 (%) was elevated from 32. 55 +/- 6.78 to 45.13 +/- 10.85; ratio of
      OKT4/OKT8 was elevated from 1.00 +/- 0.21 to 1.37 +/- 0.16; P value < 0.05, <
      0.05 and < 0.01 respectively. NK cell activity (%) was elevated from 8.20 +/-
      3.08 to 14. 0.3 +/- 4.89, P value also < 0.01. Hence, not only in group A but
      also in group B, after therapy, the parameters of OKT3,4,8, OKT4/OKT8 and NK cell
      activity (%) were all improved. But there was no significant statistical
      difference between group A and B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382739
TI  - Cytokeratin filaments of the liver of BALB/c mice as a sensitive marker of liver
      damage. Computer-aided characterization with the image analysing system "IBAS".
AB  - The cytoskeleton forms a complex structural network which is of major importance
      for both structural integrity and physiologic functions of the cell. The aim of
      the present investigation was to investigate whether hepatotoxic effects of
      nitrosamine and colchicine can be detected through changes in the cytokeratin
      filament system which is an important component of the cytoskeleton. Groups of 10
      male and 10 female newborn BALB/c mice were treated with either 25 micrograms
      dimethylnitrosamine (DMN) injected intraperitoneally on the day of birth; or with
      a daily subcutaneous injection of 0.12 micrograms/kg b.w. colchicine starting at
      ten weeks of age. A third group of mice served as untreated controls. All animals
      were held under standard laboratory conditions until necropsy at 16 weeks of age.
      The group injected with DMN received 0.05% phenobarbital with their drinking
      water after weaning. The histologic changes in the liver tissue were
      characterized by light microscopy. Changes of the cytokeratin filaments were
      visualized by the indirect immunofluorescent technique and quantified by using
      the image analysing system "IBAS". The cytokeratin filaments in the DMN group
      were markedly increased in amount and had a variety of morphological alterations.
      These effects could be measured quantitatively and did not indicate any sex
      dependent behavior. The colchicine group did not display any structural changes
      in the cytokeratin filaments but sex-dependent changes in the amount of keratin
      material was revealed by image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382740
TI  - RNA kinetics at the wound margins.
AB  - The in vitro incorporation rate of 3H cytidine was determined by autoradiography
      in vital specimens taken from cut wounds in the outer ear of rats and evaluated
      by means of a Quantimet 920. Seven rats in each group were allowed to survive for
      the same periods of time between 0 and 60 hours. The following findings were
      observed: after 10 hours survival time the cytidine incorporation rate in the
      basal cells increased significantly, while remaining unchanged in all other skin
      layers. The relationship between the higher RNA synthesis rate and the increase
      in DNA synthesis--particularly in the basal cell layer--is discussed.

PMID- 1382741
TI  - Cell membranes as barriers for antisense constructions.
AB  - The results of studies on interaction of oligonucleotides and polynucleotides
      with cell membranes are reviewed. Oligonucleotides and polynucleotides bind to
      lipid membranes in the presence of divalent cations that may result in
      spontaneous encapsulation of nucleic acids and transfer of the formed vesicles to
      the other side of the membrane. Oligonucleotides can enter eukaryotic cells and
      interact with cellular RNA and DNA. On the surface of eukaryotic cells, there are
      proteins capable of binding to nucleic acids that may be involved in
      oligonucleotide uptake. Oligonucleotides bind to cellular CD4 receptors.
      Efficient delivery into cells can be achieved by conjugation of oligonucleotides
      to lipophilic groups or by encapsulation into membrane carriers.

PMID- 1382743
TI  - Establishment of a sensitive radioimmunoassay for the detection of human IgE
      binding factor (soluble CD23).
AB  - A monoclonal antibody (mAb) specific to low-affinity receptor for IgE
      (FceRII/CD23) was established by the fusion of spleen cells of BALB/c mice
      immunized with the FceRII+ human B lymphoblastoid cell line (RPMI 8866) with
      mouse myeloma P3U1. Four mAbs, 10/3 (IgG1), 11/4 (IgG1), 12/2 (IgG2b) and 15/6
      (IgM), almost completely inhibited the IgE binding to FceRII+ cells but not to
      FceRII- cells. More directly, they were demonstrated to react only with 43-kD
      component/FceRII of the cell lysate of RPMI 8866 cells by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blot analysis. Since they have a
      different epitope specificity, a solid-phase radioimmunoassay (RIA) for the
      measurement of IgE-binding factor (IgE-BF) was established. It was found that the
      RIA with the use of 10/3 and 125I-labeled 11/4 or 12/2 gave good results in the
      detection of IgE-BF derived from B cells and monocytes as well as of T-cell
      derived IgE-BF. More importantly, serum IgE-BF was also quantitatively measured
      by this RIA. Although increased serum levels of IgE-BF were observed in atopic
      patients, serum IgE-BF was decreased rather than increased in patients with very
      high serum IgE. This phenomenon may be explained by the decreased ability of the
      patients' B cells to spontaneously release IgE-BF in vitro.

PMID- 1382742
TI  - Prospects of vaccination in autoimmune diseases.
AB  - Over the past several years, intensive efforts have been directed to define the
      pathogenic mechanisms and explore the potential immunotherapy of autoimmune
      diseases. The advances of molecular genetics and cellular immunology have now
      permitted select experimental immunotherapy using synthetic peptides, T cell
      receptor idiotypes and monoclonal antibodies. There remain many obstacles for
      success. First, the T cell receptor usage of autoreactive T cells in human
      autoimmune diseases are more heterogeneous than animal models. Clearly, there may
      not be an oligoclonal derivation of T cells in humans with autoimmune diseases.
      We foresee that the following studies might contribute to further understand
      pathogenic mechanisms and design feasible immunotherapy: (1) detailed
      characterizations of self-antigen specific T cell clones; (2) definition of
      interactions between MHC molecules and T cell receptors at the molecular level;
      (3) identification and elution of relevant disease inducing self-peptides
      complexed with MHC molecules and (4) identification of relevant genes that
      predispose to autoimmunity.

PMID- 1382744
TI  - Quantitative studies of immunofluorescent staining. VII. Quantitative reference
      standard slide for standardization of fluorescence microscopes.
AB  - We evaluated a quantitative reference standard (QRS) slide with 10-microns beads
      with different concentrations of Coulter Electronics green dye No. 1.
      Microfluorospectrophotometric readings of the QRS slides provided quantitative
      comparisons between the sensitivity of the different fluorescence microscopes.
      The visual comparisons between beads with a range of intensities of fluorescence
      of Coulter Electronics green dye No. 1 indicated that the end points vary with
      different optical systems as do the end points in standard indirect
      immunofluorescent titrations. Fluorescent emission wavelength of QRS slide beads
      gave the same peak as fluorescein-labeled beads; both differed from the peak of
      orange beads of an 'Optical Standard' slide. Since shelf life studies show no
      changes in fluorescence intensity of beads over a period of 27 months or longer,
      QRS slide beads can afford a device for standardization of fluorescence
      microscopes used for immunofluorescent tests.

PMID- 1382745
TI  - Mouse IL-3 induces histamine release from mouse peritoneal mast cells.
AB  - In this study, we have attempted to determine whether mouse peritoneal mast cells
      released histamine in response to IL-3. Recombinant mouse (m)IL-3 induced
      histamine release from mouse peritoneal mast cells in a dose-dependent fashion.
      Histamine release did not occur in the absence of phosphatidyl serine (PS), and
      was dependent on PS concentrations. The release was 14.3 +/- 3.8 and 43.5 +/-
      11.5% (mean +/- SEM, n = 5) at 1 nM IL-3 in the presence of 10 and 20
      micrograms/ml of PS. Calcium was required for the response, and in the absence of
      calcium, significant histamine release was not observed. The kinetics were slower
      than those of anti-IgE-induced response. IL-3-induced histamine release reached a
      peak within 15 min, while that by anti-IgE reached 80% of the maximum in 3 min.
      Lower concentrations of IL-3, which failed to directly induce histamine release,
      did not enhance anti-IgE-induced histamine release. Other cytokines, including
      mIL-4, mIL-5, m-granulocyte-macrophage colony-stimulating factor, human (h)IL-1
      alpha, hIL-1 beta and hIL-8, neither induced histamine release nor enhanced anti
      IgE induced histamine release. IL-4 had no capacity to enhance IL-3-induced
      histamine release. These results suggest that locally produced IL-3 might
      modulate mast cell-related inflammation through histamine release from mast
      cells.

PMID- 1382746
TI  - Factors affecting the growth and maintenance of human skin mast cells in cell
      culture.
AB  - The isolation and kinetics of survival of human mast cells from newborn and adult
      skin is described. Recombinant human interleukins and conditioned medium from
      several human cell lines were tested for their ability to maintain mast cells in
      vitro. Growth medium supplemented with IL-2, IL-4 and conditioned medium from a
      mixed lymphocyte culture enhanced mast cell survival resulting in a 30-fold
      increase in survival (relative to that obtained with non-supplemented medium) at
      7 days, and a 15-fold increase at 15 days. Cell survival for time periods longer
      than 21 days was not observed. Inclusion of cAMP, agents that elevate cAMP,
      insulin, and epidermal growth factor in supplemented growth medium prevented the
      enhanced survival by 40-70%. Incorporation of bromodeoxyuridine (BrdU) into mast
      cells in 3-day cultures demonstrated that 15% of the mast cell population was
      capable of proliferation. At 21 days, no incorporation of BrdU could be detected.
      After 3 days in culture mast cells released 16% of their histamine stores in
      response to A23187 and 10% in response to anti-human IgE. Electron microscopy of
      cultured cells at 3 days revealed cells with both intact and empty mast cell
      granules. These results demonstrate that human skin mast cells proliferate in
      response to cytokines and release histamine when stimulated with classical
      secretagogues. Since human skin mast cells retain these basic properties in
      vitro, they may be useful in further functional studies involving their
      proliferation and secretion.

PMID- 1382747
TI  - Spontaneous in vitro generation of histamine releasing factor from mononuclear
      cells of patients with hydatidosis.
AB  - We have shown that Echinococcus granulosus infection can induce an enhanced
      sensitivity of basophils to IgE-dependent stimuli. To determine whether a
      cytokine, histamine releasing factor, could account for it, we evaluated 35
      patients with active hydatidosis, 5 patients with past E. granulosus infection,
      and 20 normal volunteers. The spontaneous production of a factor in vitro that
      provoked the release of histamine from basophils was observed by mononuclear
      cells from patients with active disease, but not by those from subjects with past
      infection or from normal individuals. The histamine releasing factor was found to
      activate basophils through surface-bound IgE. It is concluded that E. granulosus
      infection induces both generation of histamine releasing factor and production of
      IgE that can bind this cytokine.

PMID- 1382748
TI  - Effect of capsaicin as a neuropeptide-releasing substance on sneezing reflex in a
      type I allergic animal model.
AB  - To elucidate the effect of capsaicin-sensitive nerve fibers, which are known to
      contain substance P (SP) and other sensory neuropeptides, on the sneezing reflex,
      we have investigated the effect of capsaicin on this reflex provoked in guinea
      pigs passively sensitized with anaphylactic antibody followed by specific antigen
      challenge. It has already been established that histamine released from mast
      cells is a reliable inducer of the sneezing reflex in type I allergy. Our
      experimental results indicated that the frequency of sneezing provoked by antigen
      challenge as well as histamine application was significantly reduced by
      pretreatment with capsaicin in a dose-dependent fashion. SP is considered to be
      one of the main neurotransmitters in sensory nerves. When the amount of SP in
      animal nasal mucosa was measured 12 h after capsaicin treatment, a marked
      reduction was noted. However, the histamine content in the nasal mucosa was not
      changed by capsaicin treatment. These data suggest that neuropeptides, especially
      SP, which are released or depleted from sensory nerves by capsaicin treatment,
      probably play an important role as neurotransmitters of the stimulant histamine
      in the development of sneezing in type I allergy.

PMID- 1382749
TI  - Response of mast cells against filarial antigens from experimentally infected
      Mastomys natelensis with Brugia malayi.
AB  - The role of antigens of Brugia malayi adult worms in induction of histamine
      release from mast cells was studied. Both peritoneal and lung mast cells were
      passively sensitized using immune serum collected from Mastomys natelensis on
      different days after infection with B. malayi. A significant release of histamine
      both with crude worm and 60-kD antigens was shown. However, the role of the 43-kD
      antigen in histamine release was comparable to that of control. When the sera
      were heat inactivated, the histamine release was minimal, thus indicating the
      heat-labile nature of the antibodies. Furthermore, the responses of peritoneal
      and lung mast cells to filarial antigens were similar.

PMID- 1382750
TI  - Intratracheal application of Sephadex in rats leads to massive pulmonary
      eosinophilia without bronchial hyperreactivity to acetylcholine.
AB  - Fourteen Brown-Norway rats were pretreated with physiological saline (n = 7) or
      500 micrograms Sephadex (n = 7) intratracheally. 24 h later, a bronchial
      provocation test was performed under pentobarbital anaesthesia using increasing
      doses of acetylcholine aerosol and the degree of bronchospasm was measured using
      a modified Konzett-Rossler method. Subsequently, leucocyte counts were determined
      in the bronchoalveolar lavage fluid (BALF), BALF cells were differentiated, and
      the chemiluminescence of the BALF leucocytes were measured. Finally, the lungs
      were removed and histologically examined. The cell count in the BALF was
      significantly (p less than 0.05) increased in the animals pretreated with
      Sephadex compared to those in the saline group (mean value +/- SEM: 0.38 +/- 0.07
      vs. 0.15 +/- 0.02 x 10(6)/ml). This difference was also reflected in the
      chemiluminescence measurements (2.51 +/- 0.53 vs. 0.20 +/- 0.03 x 10(6)
      counts/0.5 ml). In the Sephadex-treated animals there was also a significant
      increase in the absolute number of neutrophil (0.040 +/- 0.010 vs. 0.011 +/-
      0.002 x 10(6)/ml) and, in particular, eosinophil granulocytes (0.188 +/- 0.055
      vs. 0.003 +/- 0.001 x 10(6)/ml) in the total leucocytes of the BALF. Lung
      histology showed massive perialveolar and peribronchial oedema and granulomatous
      infiltrates, primarily with eosinophils, after intratracheal application of
      Sephadex; these findings were not observed in the saline group. None of these
      changes in the rats pretreated with Sephadex manifested themselves in increased
      bronchial reactivity to acetylcholine aerosol. It is uncertain if the Sephadex
      induced increase in the eosinophil count is accompanied by an activation of this
      cell population, which appears to be of importance for the occurrence of
      bronchial hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382751
TI  - [Active valvular infective endocarditis: problems of surgical treatment].
AB  - The authors analyze the results of surgical treatment of patients suffering from
      active endocarditis with impairment of the mitral, aortal and tricuspid valves
      and their combinations in 242 patients operated on during 1969 to 1989. The total
      hospital mortality is at the level of world statistics and constitutes 15.3% (37
      patients died). The main cause of the hospital mortality was acute progressive
      heart failure (48.6%). The long-term results of the surgery were examined in 202
      patients. By the 5th observation year the total survival was 73.2%, the stability
      of good results 83.6%. The defined grades of the activity of infectious process
      play an important role in the diagnosis and treatment of patients with active
      valvular infectious endocarditis.

PMID- 1382752
TI  - [Evaluation of right ventricular myocardial excursions in patients with mitral
      valve stenosis without pulmonary hypertension].
AB  - As many as 23 patients with mitral stenosis were examined intraoperatively, by
      evaluating of intracardiac hemodynamics and right ventricle myocardial
      excursions. Before mitral stenosis was corrected, 56% of patients had
      demonstrated myocardial excursion disorders. After the correction the number of
      patients with myocardial dysfunction halved. The transition of patients belonging
      to the group with abnormal myocardial excursions to the group with normal
      excursions depends on the scope of surgical intervention and pharmacological
      support. After the correction of mitral stenosis cardiogenic and pulmonogenic
      complications may mostly be seen in the patients' group showing abnormal
      myocardial excursions. It is concluded that the symptom of abnormal right
      ventricle myocardial excursions is of prognostic significance with respect to the
      development of complications in the early postoperative period.

PMID- 1382753
TI  - [Quantitative relationship between ischemic heart disease and parameters of
      energy metabolism].
AB  - The relationship between coronary heart disease, postischemic work recovery and
      tissue ATP levels as well as mitochondrial respiration rates were studied.
      Respiration of mitochondria was assessed without their isolation by using a novel
      method applying skinned fibers in physiological saline. The maximal mitochondrial
      respiration rates were unchanged during 35 min of normothermic ischemia in St.
      Thomas Hospital cardioplegic solution in the subsequent 30 min aerobic
      reperfusion period. A reversible increase in the basal respiration and a decrease
      in creatine-stimulated oxygen uptake were observed. Thus, the combined
      determination of mitochondrial respiration in situ in skinned cardiac fibers and
      tissue ATP may be a useful approach to studies of the pathogenesis of cardiac
      diseases.

PMID- 1382754
TI  - [Approaches to prevention and treatment of arterial hypoxemia in the pre
      perfusion period of radical correction of Fallot's tetrad].
AB  - Examination of central hemodynamics in patients in the preperfusion period of
      radical correction of Fallot's tetrad has demonstrated that after pericardiotomy
      and the onset of surgical manipulation on the heart there was a depression of
      circulation both during the use of intravenous total anesthesia on the basis of
      ketamine and ataralgesia. The depression was more manifest under ataralgesia. The
      depression of circulation was paralleled by the deepening of initial hypoxemia.
      Analysis of the efficacy of medicamentous agents with regard to the specific
      features of intracardiac anatomy of the outlet of the right ventricle, estimated
      intraoperatively, has established that administration of phenylephrine at a rate
      of 3 micrograms/kg favoured an increase of partial oxygen pressure and arterial
      blood saturation with hemoglobin whatever the anatomo-morphological type of
      stenosis of the outlet of the right ventricle. Propranolol promoted the
      improvement of arterial blood oxygenation but in the muscular type stenosis of
      the outlet of the right ventricle. Meanwhile the use of the drugs possessing a
      beta-adreno-stimulating effect brought about the deepening of hypoxemia.

PMID- 1382755
TI  - [Role of surfactant in the etiology of thrombohemorrhagic syndrome: problems of
      electrocoagulology].
AB  - The authors propose three hypotheses concerning heparin containing proteoglycan
      hypophase of surfactant. The source of thrombohemorrhagic syndrome (THS) they see
      in fall of the negative charge of the cells and tissues. The treatment of THS was
      performed by means of negative aero-ionization which turned effective in children
      after abdominal surgery, in burn and critical care units.

PMID- 1382756
TI  - [Role of specific brain peptide factors in the pathogenesis and compensation of
      neurologic disorders and their use in the treatment of nervous system diseases].
AB  - New concepts of the molecular mechanisms implicated in the pathogenesis and
      compensation of central motor disorders are presented. It has been shown
      experimentally that specific peptide, postural asymmetry, and inactivation
      factors, play the leading part in these processes. The detection of these
      specific factors in the cerebrospinal fluid (CSF) of patients and convalescents
      allowed one to work out and test clinically a new method of treatment (CSF
      therapy) of patients with central motor disorders of varying genesis. The results
      of the clinical observations of two patients' groups (with cerebrovascular brain
      lesions and multiple sclerosis) are provided.

PMID- 1382757
TI  - [Intracranial distension in neurosurgical pathology].
AB  - In contrast to the classic research into the problem of intracranial pressure
      based on the assumption that pressure in the cranial cavity is distributed
      uniformly, the initial methodological principle of the present work rests on the
      concept of the nonuniform distribution of pressure in the intracranial system
      both in health and disease. Comparative dynamic measurements of cerebrospinal
      fluid and brain tissue pressures were carried out in the early postoperative
      period to reveal absolute magnitudes of pressures and their correlations. Under
      examination were 166 neurosurgical patients with different levels of brain
      injury. The magnitude of cerebrospinal fluid pressure was demonstrated to depend
      on the level of brain injury. In the groups examined, intracerebral pressure of
      interstitial fluid in "normal" brain tissue was approximately the same (from -3
      to +2 mm Hg). In brain edema, that pressure increased, sometimes to a
      considerable measure (up to 50 mm Hg). Neurosurgical pathology was shown to be
      characterized by nonuniform distribution of pressure in the main intracranial
      media: brain tissue and cerebrospinal fluid, which disturbs the physiological
      ratio of these pressures. It should be mentioned that some of the structures are
      under normal pressure whereas the other ones under elevated or lowered as
      compared to the physiological norm. Such a state can be correctly characterized
      by the term "intracranial distension" bearing in mind nonuniformity of tension in
      the intracranial system, a possible one-staged coexistence in the crane of the
      areas with elevated, normal and lowered pressures.

PMID- 1382758
TI  - [A comparative experimental study of pathogenic properties of new strains of
      California encephalitis virus serogroups].
AB  - Experiments in noninbred mice, Syrian hamsters and grey monkeys were made to
      characterize the pathogenic properties of new strain of the California
      encephalitis serogroup isolated for the first time on the island of Taimir, in
      the Murmansk, Leningrad, Tver regions and in Karelia. All the strains displayed
      marked tropism for the CNS. The strains isolated in the northern regions of this
      country turned out more pathogenic for the animals. The strain Leiv-12812 Kl
      (isolated in the Tver region) differed from the remaining ones in more pronounced
      pathogenicity for the monkeys, as well as in the site and intensity of brain
      lesions. The persistence of the virus in hamsters organs may play a role of a
      reservoir of infection in nature.

PMID- 1382759
TI  - [Role of enkephalins in the mechanism of anti-arrhythmia effects of adaptation in
      acute myocardial ischemia].
AB  - Adaptation of rats to cold and physical exercise prevented ventricular
      fibrillation (VF) caused by the occlusion of the left anterior coronary artery.
      In the heart of adapted rats with acute myocardial ischemia, myocardial
      enkephalins increased whereas the level of cAMP declined as compared to
      nonadapted animals. Injection of dalargin before the occlusion of the coronary
      artery in rats prevented both VF and a decrease of VF threshold. The peptide
      averted the rise of cAMP content in the heart during acute myocardial ischemia.
      The data obtained suggest that the rise of endogenous myocardial enkephalins may
      have an important role in antiarrhythmic action of adaptation. It is assumed that
      antiarrhythmic effect of enkephalins may be related to the restriction of
      sympathetic influence on the heart.

PMID- 1382760
TI  - [Status metric analysis of epidemiological data on congenital developmental
      defects caused by environmental pollution].
AB  - Status metry was used to determine the portion of congenital developmental
      abnormalities (CDA) of obscure etiology (probably of mutation origin) among the
      total number of CDA in 3 cities of the Ukraine. The contribution of CDA
      determined by new mutations correlates with the reported data and corresponds
      with the level of atmospheric air pollution in the cities under study. Status
      metry made it also possible to define the tendencies and magnitude of the
      influence of factors involved in CDA formation. The conclusion is made about
      adequacy of the use of status metry for indirect estimation of the rate of the
      mutation process and its modification under the effect of environmental
      pollution.

PMID- 1382761
TI  - [Possibility of selective binding of HIV-1 infected cells by immunosorbents].
AB  - A study was made of a possibility of specific sorption of HIV-1 infected cells
      with gamma-fraction of AIDS patients' serum containing high titer-specific
      antibodies, immobilized on the silica matrix (C-3). The laboratory tests were
      made with the use of the monocyte culture [symbol: see text] chronically infected
      with HIV-1. In addition to a decrease of the cell count after sorption, there was
      a decline of the activity of antigen material in the samples (to 43% of the
      initial). The selectivity rates were 0.92 for immunosorbents and 0.29 for
      sorbents of the control group, that confirms and increase of the delay of the
      cells expressing HIV-1 proteins on a column with the immobilized gamma-fraction
      of AIDS patients' serum. The use of the synthesized immunosorbents in vivo may
      appear debatable. However, this method can be employed for preparative purposes.

PMID- 1382762
TI  - [Dietary intake of Cs-137 and Sr-90 by the population of the Gomel region,
      Byelarus, 1986-1989].
AB  - The authors provide the results of measuring the content of radionuclides in
      foods in the first 4 years after the Chernobyl accident and the data on the diet
      of the population. Pollution of foods was demonstrated to decrease with time. The
      supply of 137Cs to the body fell 3-fold from 1986 to 1989. The rejection of foods
      in the most polluted Vetkovsk and Narovlyansk regions made it possible to reduce
      3-6-fold the mean daily supply of 137Cs with the diet and up to 2-fold the supply
      of 90Sr.

PMID- 1382763
TI  - [Study of health status of personnel servicing ultra-high power installations].

PMID- 1382764
TI  - [Glucocorticoid receptor mechanism of regulation of the activity of angiotensin
      converting enzyme and new prospects in the treatment of cardiovascular diseases].
AB  - Based on the concept of glucocorticoid-receptor induction of angiotensin
      converting enzyme (ACE), approaches to inhibiting enzyme induction with drugs
      that suppress the function of type II cytoplasmic glucocorticoid receptors,
      (genuine glucocorticoid receptors), are suggested. Three types of inhibiting the
      function of type II glucocorticoid receptors by drugs were distinguished. Type I
      is characterized by competition of the drugs with natural and synthetic
      glucocorticoids for interaction with glucocorticoid receptors (cortexolone,
      progesterone); type II is determined by irreversible inactivation of type II
      glucocorticoid receptors (aminazine, tisercin); type III is related to an
      increase of interaction of transcorticoid receptors with natural glucocorticoids
      which is accompanied by a reduction of the interaction of natural glucocorticoids
      with genuine glucocorticoid receptors (analgin, amidopyrine). It has been
      established that the drugs that provoke irreversible inactivation of the function
      of type II glucocorticoid receptors decrease ACE activity in blood plasma and in
      the lungs, that may serve the main reason for their high hypotensive effect in
      arterial hypertension. A concept is advanced, providing evidence for the use of
      the classical ACE inhibitors and of type II glucocorticoid receptor inhibitors.

PMID- 1382765
TI  - Maternal serum anti-D antibody concentration and assessment of rhesus
      isoimmunisation.

PMID- 1382766
TI  - Colorectal cancer.

PMID- 1382767
TI  - Cytokines and cancer.

PMID- 1382768
TI  - Antenatal maternal serum screening for Down's syndrome: results of a
      demonstration project.
AB  - OBJECTIVES: To assess the implementation of antenatal screening for Down's
      syndrome in practice, using individual risk estimates based on maternal age and
      the three serum markers: alpha fetoprotein, unconjugated oestriol, and human
      chorionic gonadotrophin. DESIGN: Demonstration project of Down's syndrome
      screening; women with a risk estimate at term of 1 in 250 or greater were
      classified as "screen positive" and offered diagnostic amniocentesis. SETTING:
      Hospital and community antenatal clinics in four health districts in London.
      SUBJECTS: 12,603 women of all ages with singleton pregnancies seen between
      February 1989 and the end of May 1991, with follow up of the outcome of pregnancy
      completed to the end of 1991. MAIN OUTCOME MEASURES: Uptake of screening,
      detection rate for Down's syndrome, false positive rate, odds of being affected
      given a positive result, and uptake of amniocentesis in women with positive
      screening results, together with the costs of the screening programme. RESULTS:
      The uptake of screening was 74%. The detection rate was 48% (12/25), and the
      false positive rate was 4.1%, consistent with results expected from previous work
      based on observational studies. There was a loss of detection due to the
      selective use of ultrasound scans among women with positive screening results.
      One affected pregnancy occurred among 205 reclassified as negative; this
      illustrated the danger of false negatives occurring in this group and lends
      weight to the view that if an ultrasound estimate of gestational age is used it
      should be carried out routinely on all women rather than selectively among those
      with positive results. The estimated cost of avoiding the birth of a baby with
      Down's syndrome was about 38,000 pounds, substantially less than the lifetime
      costs of care. CONCLUSION: Antenatal maternal serum screening for Down's syndrome
      is effective in practice and can be readily integrated into routine antenatal
      care. It is cost effective and performs better than selection for amniocentesis
      on the basis of maternal age alone.

PMID- 1382769
TI  - Pregnancy associated plasma protein A in Down's syndrome.

PMID- 1382770
TI  - Pregnancy associated plasma protein A in Down's syndrome.

PMID- 1382772
TI  - Opposing effects of heparin with TGF-beta or aFGF during repair of a mechanical
      wound of human endothelium. Influence of cAMP on cell migration.
AB  - The effects on vascular wound repair in vitro of aFGF and TGF-beta, growth
      factors having opposite influences on endothelial cell growth and angiogenesis,
      were studied using as a model a mechanical lesion of confluent endothelium.
      Modulation by heparin of the activities of these growth factors during the repair
      process was also examined. Whereas heparin alone inhibited repair by lowering
      both cell proliferation and cell migration, TGF-beta alone mainly inhibited cell
      proliferation. When added together, TGF-beta and heparin exerted a combined
      inhibitory effect resulting in a residual lesion 50% larger than in controls.
      aFGF alone accelerated lesion coverage and this effect was enhanced by 40% over
      control values when heparin was added with aFGF. This acceleration was slightly
      (less than 10%) but consistently diminished by TGF-beta. Cell density in
      confluent unwounded areas was increased by 40% in the presence of aFGF, but TGF
      beta diminished cell density by 20%. A small (30%) increase in intracellular cAMP
      was measured whenever aFGF was present during the repair process. In comparison,
      intracellular cAMP inducing agents (forskolin, dbcAMP) accelerated cell migration
      by 20% during lesion recovery without affecting cell proliferation or density.
      The present results show that the inhibitory effects of TGF-beta during vascular
      wound repair are opposed by aFGF. Furthermore, heparin (or heparan sulfates in
      vivo) modulates growth factors having activating or inhibiting functions and thus
      plays a regulatory role during the repair process. cAMP-inducing substances other
      than growth factors are able to accelerate cell migration.

PMID- 1382771
TI  - Diagnostic confusion in diabetes with persistence of fetal haemoglobin.

PMID- 1382774
TI  - Control of acute respiratory infections in the Americas.

PMID- 1382775
TI  - International meeting on the Eradication of Bovine Tuberculosis in the Americas.

PMID- 1382773
TI  - Child mental health in the Americas: a public health approach.
AB  - The systematic, population-wide application of preventive measures based on what
      is known about the causes and outcomes of psychiatric disorders can markedly
      reduce morbidity from mental ill health among children in the Americas. The
      actions proposed here rely partly upon increasing access for all women and their
      children to thoroughly tested obstetric and pediatric care; in part they depend
      on improving nutrition and opportunities for cognitive stimulation; and in part
      they call for enhancing the mental health skills of primary care practitioners by
      appropriate in-service training. There are limits to our knowledge and to the
      effectiveness of some of our interventions; nonetheless, the greatest barrier to
      better child mental health is failure to muster the political will to apply what
      is known to the care of mothers and children in all sectors of society.

PMID- 1382776
TI  - Role of the hospital support team.
AB  - The hospital support team is a multidisciplinary team through which the expertise
      of hospice care can be extended to the acute hospital situation. This article
      highlights the aims of such a team and the expertise of different members,
      emphasizing the advisory role and the importance of 'role-modelling'.

PMID- 1382777
TI  - Involvement of substance P present in primary afferent neurones in modulation of
      cutaneous blood flow in the instep of rat hind paw.
AB  - 1. The participation of small-diameter afferent fibres in the microcirculatory
      haemodynamics of cutaneous tissue was examined by studies on the effects of
      antidromic stimulation of primary afferent neurones on cutaneous blood flow (CBF)
      and tachykinin release into the subcutaneous space in the instep of the hind paw
      of rats. 2. Antidromic stimulation of the sectioned sciatic nerve induced a
      biphasic flow response, an initial transient decrease followed by an increase,
      with no alteration in the blood pressure. 3. Neither phase was affected by
      pretreatment with phentolamine (0.1 mg kg-1, i.a.), propranolol (0.5 mg kg-1,
      i.a.), atropine (0.5 mg kg-1, i.a.), methysergide (0.5 mg kg-1, i.a.) or
      mepyramine (10 mg kg-1, i.a.) plus cimetidine (10 mg kg-1, i.a.), but both were
      significantly inhibited by pretreatment with capsaicin (50 mg kg-1, s.c.). 4.
      Spantide (1-2 mumol kg-1, i.a.), a substance P (SP) antagonist, reduced the basal
      CBF, and also inhibited both phases of the biphasic flow response evoked by
      antidromic stimulation of the sectioned sciatic nerve. 5. Intra-arterial infusion
      of SP (0.5 mumol kg-1, i.a.) induced a biphasic flow response similar to that
      elicited by antidromic stimulation of the sectioned sciatic nerve. 6. Antidromic
      stimulation of the sectioned sciatic nerve caused a marked increase in SP release
      into the subcutaneous perfusate of the instep of the rat hind paw, but no
      detectable increase in neurokinin A release.7. We suggest that SP and its
      receptors are mainly responsible for the vascular response induced by stimulation
      of the sectioned sciatic nerve, and that small-diameter afferent fibres
      containing SP tonically regulate vascular tone in cutaneous microvessels.

PMID- 1382778
TI  - Structure-activity relations of amiloride and its analogues in blocking the
      mechanosensitive channel in Xenopus oocytes.
AB  - 1. Patch clamp recording techniques have been used to compare the block caused by
      amiloride and some of its structural analogues of the mechanosensitive (MS)
      cation selective channel in frog (Xenopus laevis) oocytes. 2. Like amiloride, the
      amiloride analogues dimethylamiloride (DMA), benzamil and
      bromohexamethyleneamiloride (BrHMA) block the MS channel in a highly voltage
      dependent manner. 3. All analogues tested were more potent blockers than
      amiloride with IC50's of 500 microM (amiloride), 370 microM (DMA), 95 microM
      (benzamil) and 34 microM (BrHMA). 4. Hill plots gave Hill coefficients of 2
      (amiloride), 1.8 (DMA), 1 (benzamil) and 1.2 (BrHMA) indicating that the binding
      of two ligand molecules may be necessary for the block caused by amiloride, DMA
      and possibly BrHMA whereas only a single ligand molecule may be required for the
      block by benzamil. 5. The potential use of BrHMA as a light-activated, covalent
      label of the MS channel protein is discussed. 6. The amiloride analogue
      'fingerprinting' of the blocking site on the MS channel indicates it is
      structurally different from previously described amiloride-sensitive ion
      transport pathways but may be related to the amiloride binding site on outer hair
      cells of the ear.

PMID- 1382779
TI  - Evidence for a glutamate receptor of the AMPA subtype which mediates insulin
      release from rat perfused pancreas.
AB  - 1. The effect of L-glutamate has been studied on insulin secretion by the
      isolated perfused pancreas of the rat. The glutamate receptor subtype involved
      has been characterized. 2. In the presence of a slightly stimulating glucose
      concentration (8.3 mM), L-glutamate (5 x 10(-5)-4 x 10(-3) M) induced an
      immediate, transient and concentration-dependent insulin response. On the other
      hand, in the presence of a non stimulating glucose concentration (2.8 mM), L
      glutamate (10(-3) M) did not modify the basal insulin secretion. 3. The three non
      NMDA receptor agonists, kainate (10(-4)-10(-3) M), alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA, 5 x 10(-5)-10(-4) M) and quisqualate (5 x 10(-6)
      5 x 10(-5) M) all provoked a transient and concentration-dependent insulin
      response from pancreas perfused with 8.3 mM glucose. Compared with glutamate,
      kainate exhibited a similar efficacy, whereas AMPA and quisqualate elicited only
      a 3 fold lower maximal insulin response. In contrast, NMDA (10(-4)-10(-3) M) was
      ineffective. 4. An antagonist of non-NMDA receptors, 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX; 5 x 10(-5) M) totally prevented the stimulatory effect of L
      glutamate (4 x 10(-4) M) and kainate (2 x 10(-4) M). In contrast, the NMDA
      receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10
      imine ((+) MK801) was without effect. 5. The insulin secretory effect of
      glutamate (4 x 10(-4) M) was not affected by atropine (3 x 10(-7) M) or
      tetrodotoxin (3 x 10(-6) M). 6. Quisqualate at a high maximally effective
      concentration (4 x 10(-4) M) inhibited glutamate (10(-3) M) or kainate (4 x 10(
      4) M)-induced insulin release. 7. This study shows that L-glutamate stimulates
      insulin secretion in rat pancreas, by acting on an excitatory amino acid receptor
      of the AMPA subtype.

PMID- 1382780
TI  - Cholinoceptor regulation of cyclic AMP levels in bovine adrenal medullary cells.
AB  - 1. The regulation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels by
      cholinoceptors has been studied in cultured bovine adrenal medullary cells. 2.
      Acetylcholine (100 microM), nicotine (10 microM) and dimethylphenylpiperazinium
      (20 microM) each increased cellular cyclic AMP levels 2 to 4 fold over 5 min in
      the absence of phosphodiesterase inhibitors. The muscarinic agonist acetyl-beta
      methylcholine (100 microM) had no effect either on its own or on the response to
      nicotine. The responses to acetylcholine and nicotine were unaffected by atropine
      (1 microM) but were abolished by mecamylamine (5 microM). 3. Cellular cyclic AMP
      increased transiently during continuous exposure to nicotine (1-20 microM), with
      the largest response seen after 5 min, a smaller response after 20 min, and no
      change in cyclic AMP levels seen after 90 or 180 min. The maximal response after
      5 min stimulation was seen with 5-10 microM nicotine and the EC50 was about 2
      microM. In contrast, extracellular cyclic AMP levels did not change after 5 or 20
      min stimulation with nicotine, but increased slightly after 90 min and further
      after 180 min. 4. The cellular cyclic AMP response to nicotine (10 microM) was
      unchanged or weakly enhanced in the presence of the unselective phosphodiesterase
      inhibitor, isobutylmethylxanthine, and was unchanged in the presence of rolipram.
      Nicotine did not interact synergistically with low concentrations of forskolin.
      The response was however completely abolished in the absence of extracellular
      Ca2+.

PMID- 1382781
TI  - Pharmacological characterization of non-NMDA subtypes of glutamate receptor in
      the neonatal rat hemisected spinal cord in vitro.
AB  - 1. A grease-gap technique was used to record depolarizing responses to alpha
      amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA), kainate and N-methyl-D
      aspartate (NMDA) in the hemisected spinal cord of the neonatal rat. The
      pharmacology of non-NMDA subtypes of glutamate receptor was investigated with the
      novel quinoxalinedione, 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)-quinoxaline
      (NBQX) and with a series of barbiturates. 2. NBQX antagonized AMPA- and kainate-,
      but not NMDA- induced depolarizations. The near parallel shifts of the major part
      of the dose-response curves for AMPA and kainate by NBQX gave pA2 values (+/-
      s.e.) of 6.7 +/- 0.2 and 6.8 +/- 0.2 respectively, consistent with a common site
      of action for these two agonists. 3. Below the 50% level at which these pA2
      values were calculated, however, an NBQX-resistant plateau was seen within the
      kainate, but not the AMPA, dose-response curve. 4. In decreasing order of
      potency, methohexitone, secobarbitone, thiopentone, pentobarbitone and
      phenobarbitone preferentially reduced kainate-, rather than AMPA- and NMDA-,
      induced depolarizations. Methohexitone was also the most selective with IC50S
      against kainate, AMPA and NMDA of 31 +/- 7, 172 +/- 47 and greater than 200
      microM respectively. 5. The NBQX-resistant plateau seen within the kainate dose
      response curve was reduced by methohexitone. Kainate antagonism by methohexitone
      was not reduced by 50 microM picrotoxin. 6. We conclude that, while mixed agonist
      actions may hamper demonstration of antagonist selectivity, depolarizations
      induced by the non-NMDA ionotropic agonists, AMPA and kainate, are mediated in
      part via distinct receptors.

PMID- 1382782
TI  - Effects of a potassium channel opener (SDZ PCO 400) on guinea-pig and human
      pulmonary airways.
AB  - 1. SDZ PCO 400 evoked dose-related relaxation of isolated airway smooth muscle.
      For human bronchus precontracted by endogenous tone or addition of carbachol (10(
      5) M), IC50 values were 1.74 microM and 1.82 microM respectively. With guinea-pig
      trachea contracted by endogenous tone, a comparable IC50 (1.79 microM) was
      observed, but no IC50 (less than 100 microM) could be determined following
      contraction by carbachol (10(-6) M). 2. Airway obstruction induced by intravenous
      bombesin in the anaesthetized ventilated guinea-pig was diminished by intravenous
      injection of SDZ PCO 400 (ID50 54 micrograms kg-1) or by introduction into the
      duodenum (ID50 1.0 mg kg-1). Inhalation of nebulized SDZ PCO 400 (0.1 mg kg-1)
      diminished airway obstruction due to intravenous injection of histamine (3.2-5.6
      micrograms kg-1) for up to 20 min. 3. Increased bronchoconstrictor responses to
      bombesin (180-240 ng kg-1) following intravenous infusion of platelet activating
      factor (PAF) or (+/-)-isoprenaline, or to histamine (1.0-3.2 micrograms kg-1)
      following intravenous injections of immune complexes, were suppressed following
      concomitant intravenous infusion of SDZ PCO 400 (ID50 0.3 mg kg-1 h-1, 1.0 mg kg
      1 h-1 and 0.1 mg kg-1 h-1 respectively). 4. Intravenous injection of SDZ PCO 400
      (0.1 mg kg-1) effected transient (less than 10 min) inhibition of histamine
      induced bronchospasm, yet diminished, for prolonged periods [up to 40 min] the
      enhanced bronchoconstrictor responses to histamine that followed intravenous
      injections of immune complexes.The capacity of SDZ PCO 400 to resolve such
      established airway hyperreactivity was prevented by prior intraduodenal
      instillation of a potassium channel antagonist, glibenclamide (30 mg kg-').5. In
      sensitized guinea-pigs, SDZ PCO 400 inhaled as a dry powder (5.7 mg kg-')
      suppressed development of allergic airway hyperreactivity to histamine (1.8
      3.2;pg kg-', i.v.), but failed to diminish accumulation of eosinophils or other
      inflammatory cells within the airway lumen 24 h after inhalation of ovalbumin.6.
      Preincubation (30 min) of isolated sensitized trachea of guinea-pig with SDZ PCO
      400 (10-5-10-4M) did not influence contractile responses to ovalbumin. However in
      anaesthetized sensitized guinea-pigs,insufflation of SDZ PCO 400 (1.25 mg) as a
      powder substantially diminished airway obstruction that followed inhalation of
      ovalbumin. This effect was prevented by prior vagal section.7. It is concluded
      that SDZ PCO 400 reduces airway obstruction not only through direct actions on
      airway smooth muscle but also by impairing the expression of airway
      hyperreactivity, without directly influencing inflammatory events in the airways.

PMID- 1382783
TI  - Effects of imipramine on the transient outward current in rabbit atrial single
      cells.
AB  - 1. The effects of imipramine on action potential characteristics and transient
      outward potassium current (It) of rabbit isolated atrial myocytes were studied
      using the whole-cell configuration of the patch-clamp technique. 2. Imipramine, 3
      microM, decreased action potential amplitude and lengthened the action potential
      duration measured at 50% of repolarization, whereas it did not modify the final
      phase of repolarization or the resting membrane potential. These results are
      similar to those reported in multicellular rabbit atrial preparations. 3.
      Imipramine, 0.1-100 microM, induced a concentration-dependent inhibition of the
      peak amplitude of It, a shortening of the time to peak current and an increase in
      the inactivation rate. The acceleration of the current inactivation is to a major
      extent responsible for the decrease in the integral of the outward current
      measured at 50 ms after the start of the pulse. 4. The drug-induced block of It
      was not associated with changes in the voltage-dependence of the steady-state
      inactivation curve or in the process of recovery from inactivation of the
      current. Extrapolation to zero block shows that imipramine did not block It
      before its activation at the onset of the depolarization. These results suggested
      that imipramine does not affect the inactivated or the resting state of It
      channels. 5. It is concluded that in rabbit isolated atrial cells, imipramine
      inhibits It and that this effect is responsible for the lengthening of the action
      potential duration produced by this drug.

PMID- 1382784
TI  - Effect of the beta-adrenoceptor agonist clenbuterol and phytohaemagglutinin on
      growth, protein synthesis and polyamine metabolism of tissues of the rat.
AB  - 1. The kidney bean lectin, phytohaemagglutinin (PHA), induced a marked atrophy of
      skeletal muscle which was evident from the changes in tissue composition
      (protein, RNA, DNA and polyamine content) and from the reduction in weight and
      protein synthesis of hind leg muscles of rats fed on kidney bean-diets for four
      days. The beta-adrenoceptor agonist, clenbuterol, induced skeletal muscle
      hypertrophy by transiently stimulating protein synthesis. As a consequence, the
      muscle loss caused by a short exposure to PHA was, in part, ameliorated by
      clenbuterol treatment. 2. Cardiac muscle was affected to a lesser extent than
      skeletal muscle by both clenbuterol and the lectin. However, there was evidence
      that protein synthesis in heart was reduced by PHA. 3. PHA had opposite effects
      on the gut, the lectin-induced hyperplasia of the jejunum was accompanied by a
      large increase in protein synthesis. Clenbuterol alone had no effect on the
      jejunum whereas a combination of PHA and clenbuterol appeared to exacerbate the
      effect of the lectin on gut. 4. Both the lectin-induced gut growth and the
      hypertrophy of skeletal muscle caused by clenbuterol were preceded by the
      accumulation of polyamines in the respective tissues. Of particular note was the
      observation that a significant increase in the proportion of the
      intraperitoneally injected 14C-labelled spermidine or putrescine taken up by the
      growing tissues could be detected by the second day. Therefore, the measurement
      of uptake of labelled polyamines may be used as a sensitive indicator of early
      alterations in tissue metabolism.

PMID- 1382785
TI  - Ca2+ release from isolated sarcoplasmic reticulum of guinea-pig psoas muscle
      induced by K(+)-channel blockers.
AB  - A Ca(2+)-sensitive electrode was used to measure the Ca2+ concentration of the
      medium containing the heavy fraction of the fragmented sarcoplasmic reticulum
      (SR) prepared from guinea-pig psoas muscle. Among K(+)-channel blockers tested, 4
      aminopyridine (4-AP), tetraethylammonium (TEA) and charybdotoxin elicited Ca2+
      release from the SR, but apamin and glibenclamide did not. These results suggest
      that a reduction of SR K+ conductance leads to Ca2+ release from the SR.

PMID- 1382786
TI  - The neuroprotective effect of a nitric oxide inhibitor in a rat model of focal
      cerebral ischaemia.
AB  - Recent data showed that glutamate toxicity in primary cortical cultures is
      mediated by nitric oxide. In order to investigate the effect of inhibition of NO
      synthase on focal cerebral ischaemia in rats, we studied the histological
      consequences of a middle cerebral artery (MCA) occlusion after post-operative
      treatment with NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide
      synthase. We found a significant reduction of cortical (-43%) and striatal (-25%)
      necrotic volumes induced by MCA occlusion, indicating that NO synthesis plays an
      important role in the neurotoxic cascade leading to neuronal damage after focal
      cerebral ischaemia in rats.

PMID- 1382787
TI  - Characterization and localization of nitric oxide synthase in non-adrenergic non
      cholinergic nerves from bovine retractor penis muscles.
AB  - 1. Partially purified soluble nitric oxide (NO) synthase was isolated from the
      bovine retractor penis muscle (BRP), a tissue in which the inhibitory response to
      non-adrenergic non-cholinergic nerve (NANC) stimulation appears to be mediated by
      NO or NO-like material. 2. NO synthase from BRP used L-arginine as a substrate,
      required NADPH, tetrahydrobiopterin, and FAD as co-factors and was
      Ca2+/calmodulin-dependent. The activity of NO synthase was inhibited by NG-methyl
      L-arginine and NG-nitro-L-arginine, and haemoglobin blocked the effect of NO
      formed by the enzyme. 3. On reducing SDS polyacrylamide gel electrophoresis the
      apparent molecular mass of NO synthase from BRP was 160 +/- 2 kDa, which is
      similar to that of the cerebellar NO synthase. Protein immunoblot and
      immunoprecipitation showed that NO synthase from BRP cross-reacted with the
      selective antiserum to neuronal NO synthase from rat cerebellum. 4.
      Immunohistochemistry using the same antiserum demonstrated that NO synthase in
      BRP was located exclusively within nerve fibres. Thus, autonomic nerves
      synthesizing the NANC neurotransmitter seem to contain an isoform of NO synthase
      which is similar to that from rat cerebellum.

PMID- 1382788
TI  - Involvement of inflammatory mediators in the airway responses to trimellitic
      anhydride in sensitized guinea-pigs.
AB  - 1. We examined the effect of various pharmacological agents on the acute
      bronchoconstrictor response and airway microvascular leakage in a model of guinea
      pig sensitization to trimellitic anhydride (TMA) a cause of low molecular weight
      occupational asthma in man. 2. Guinea-pigs were given intradermal injections of
      0.1 ml of 0.3% TMA in corn oil; 21-28 days later, anaesthetized guinea-pigs were
      challenged with TMA conjugated to guinea-pig albumin by tracheal instillation.
      Changes in lung resistance were measured and airway microvascular leakage was
      quantified by measuring the extravasation of Evans blue dye into the airway
      tissue. 3. Sensitized guinea-pig (n = 9 in each group) were pretreated with
      chlorpheniramine (2.5 mg kg-1, i.v.), WEB 2086 (10 micrograms kg-1, i.v.), BW 4AC
      (50 mg kg-1, i.p.), nedocromil sodium (2% aerosol for 60 s) or vehicle alone. 4.
      Pretreatment with chlorpheniramine inhibited both the acute bronchoconstrictor
      response and the increase in airway microvascular leakage. WEB 2086 and
      nedocromil sodium partially inhibited the bronchoconstrictor response but had no
      significant effect on airway microvascular leakage. BW 4AC caused a non
      significant reduction of the bronchoconstrictor response and airway microvascular
      leakage. 5. These results indicate that both the bronchoconstrictor response and
      the airway microvascular response in this model of sensitization is mediated to a
      large extent by histamine. PAF but not 5-lipoxygenase products also partially
      mediates the bronchoconstrictor response but not the airway microvascular
      leakage. Nedocromil sodium partially inhibits the bronchoconstrictor response
      only.

PMID- 1382789
TI  - The cardiodepressant and vasodepressant effects of tumour necrosis factor in rat
      isolated atrial and aortic tissues.
AB  - 1. The ability of recombinant human tumour necrosis factor-alpha (rec huTNF) to
      elicit cardiodepressor and vasodepressor effects in rat isolated tissues was
      investigated. 2. rec huTNF (3 x 10(-11)-3 x 10(-8) M) administered directly to
      the organ bath, caused a concentration-dependent relaxation of the isoprenaline
      induced inotropic response in electrically stimulated rat left atria. This
      occurred within 20 min of administration. In contrast, rec huTNF was without
      effect on the chronotropic response to isoprenaline in isolated spontaneously
      beating atria. 3. rec huTNF (1 microgram kg-1) was also given systemically to
      rats and the atria studied in vitro. Only 60 min of rec huTNF pretreatment was
      sufficient to cause a marked attenuation of the isoprenaline-induced inotropic
      response. This effect was not further augmented when rats were pretreated with
      rec huTNF for 24 h. 4. In isolated aortic rings taken from rats 60 min after rec
      huTNF (1 microgram kg-1, i.v.) administration, there was no effect seen on the
      constriction induced by phenylephrine in either endothelium-intact or denuded
      tissues. In addition, any responses to L-arginine or NG-nitro-L-arginine methyl
      ester (L-NAME) administration were unaffected by rec huTNF pretreatment. 5. In
      aortic rings taken from rats 24 h after rec huTNF administration, the
      phenylephrine-induced constriction was significantly attenuated in tissues with
      an intact endothelium. Furthermore, the relaxation to subsequent L-arginine
      administration was greater in these tissues than in those saline-treated rats. In
      addition, in both endothelium-intact and denuded tissues, the vasoconstrictor
      response to L-NAME (10-3M) was significantly augmented. 6. These data suggest
      that rec huTNF possesses both cardiodepressant properties with a rapid onset of
      action and vasodepressant properties with a slow onset of action. The latter
      could be mediated through the induction of a non-constitutive form of the NO
      synthase enzyme present within the vascular wall.

PMID- 1382791
TI  - Small cell carcinoma of the prostate.

PMID- 1382790
TI  - Endotoxin-induced vasodilatation in anaesthetized rat skin involves nitric oxide
      and prostaglandin synthesis.
AB  - 1. The effect of intradermally injected endotoxin on skin blood flow was
      investigated in anaesthetized male Wistar rats in vivo. 2. Local skin blood flow
      changes were measured hourly for 6 h in the shaved dorsal skin with a laser
      Doppler flow probe and compared to changes in control sites which had been
      injected with 100 microliters of phosphate-buffered saline. By 3 h, skin blood
      flow increased above basal by 129 +/- 27% and 186 +/- 29% with 1 and 10
      micrograms of endotoxin respectively. Blood flow remained significantly elevated
      at 6 h, the corresponding figures being 129 +/- 24% and 154 +/- 31% (P less than
      0.05, n = 6 rats, mean +/- s.e.mean). 3. In further experiments, the response to
      3 micrograms of endotoxin was measured at 4 h and treatment with a cyclo
      oxygenase inhibitor, nitric oxide synthase inhibitors or a topical steroid all
      significantly inhibited this response (P less than 0.05 in each case, n = 6 rats
      in each group with duplicate sites in each animal). 4. Indomethacin 3 x 10(-9)
      mol per site injected 3.5 h after injection of endotoxin suppressed the mean 4 h
      response to endotoxin by 78%; NG-nitro-L-arginine methyl ester (L-NAME) 10(-7)
      mol per site suppressed the response by 95%; NG-monomethyl-L-arginine (L-NMMA)
      10(-7) mol per site suppressed the response by 50%; whereas the D-isomer of NG
      monomethyl-arginine 10(-7) mol per site had no significant effect.5. Topical
      application of the corticosteroid, betamethasone 17-valerate (1% solution) 18 h
      before injection of endotoxin inhibited the mean 4 h response to endotoxin by 66%
      and the 6 h response by 48%.6. In the same model, the vasodilator response to
      arachidonic acid was inhibited by both indomethacin and nitric oxide synthase
      inhibitors (P<0.05 in each case).7. These data suggest that the microcirculatory
      vasodilator response to endotoxin and arachidonic acid injected locally involves
      both nitric oxide synthase and cyclo-oxygenase in this in vivo model.

PMID- 1382792
TI  - Urological audit: the role for an aggressive approach to high grade superficial
      bladder tumours.
AB  - A retrospective study was undertaken of the different treatment modalities for
      bladder tumours under the care of 3 consultants in the urology department of a
      district general hospital. The aim was to review the results of the various forms
      of treatment. In all, 261 patients' case records were reviewed and 19 variables
      extracted. There was an average delay of 4.2 months from the onset of symptoms to
      the initial cystoscopy. Over 50% of high grade tumours were invasive on initial
      presentation (G3T2/G3T3). A range of treatments for the more aggressive tumours
      was adopted by the urologists, ranging from a conservative resection (TURBT) to
      an aggressive approach (cystourethrectomy) at the earliest sign of progression. A
      strong association between aggressive treatment and higher survival was noted.
      This study has proved valuable in demonstrating to the urology team the value of
      routine audit and questioning "established" surgical practice. As a result, a
      more standard regime for the treatment of bladder tumours has been advocated and
      a prospective randomised controlled trial will be introduced.

PMID- 1382793
TI  - Transurethral incision versus transurethral resection of the prostate. A
      subjective and objective analysis.
AB  - A prospective study was undertaken comparing transurethral incision of the
      prostate (TUIP) with transurethral resection (TURP) in the treatment of 220
      patients with urinary obstruction caused by a small, benign prostate. Patients
      were managed alternately by TUIP and TURP, and their symptoms and urodynamic
      findings evaluated before and after surgery. Subjectively and objectively, the
      results were comparable in both groups. Pre- and post-operative complications
      were significantly less for the TUIPs than the TURPs. TUIP was significantly
      better than TURP in terms of shorter operating time, duration of hospitalisation
      and reduced need for transfusion. We recommend TUIP as the operation of choice
      for the relief of obstruction in the presence of a small, benign prostatic
      enlargement.

PMID- 1382794
TI  - Localised deep microwave hyperthermia in the treatment of benign prostatic
      hyperplasia: long-term assessment.
AB  - A group of 133 patients with benign prostatic hyperplasia who were either poor
      operative risks or who had refused surgery underwent localised deep microwave
      hyperthermia, without supplementary drugs. In 59% of patients who had had an
      indwelling catheter, freedom from urological obstruction and satisfactory voiding
      were maintained for 7 years and catheterisation was not required. In patients
      with severe prostatic symptoms, 65% showed general improvement and satisfactory
      voiding for 8 years. There were no side effects. Patients who relapsed were given
      a second course of treatment and 75% responded positively. This positive response
      and the lack of side effects suggest that localised deep microwave hyperthermia
      may be an effective alternative to surgery in the management of high risk
      patients and those who are reluctant to undergo surgery.

PMID- 1382795
TI  - Inter-relation between measurement of serum prostatic specific antigen and
      transrectal ultrasound in the diagnosis of benign prostatic hyperplasia and
      prostatic cancer.
AB  - Serum prostatic specific antigen (PSA) and ultrasound-determined prostatic volume
      (UPV) were measured in 50 patients with histologically proven benign prostatic
      hyperplasia (BPH) and in 40 patients with histologically proven prostatic cancer
      of whom 17 had evidence of distant metastases (M1) and 23 did not (M0). A good
      correlation between log PSA and UPV was demonstrated in the BPH group and
      rearrangement of the linear regression equation allowed calculation of a single
      variable--the log PSA corrected to a standard prostate volume for any given
      individual. A volume-corrected PSA correctly identified all patients with M1
      disease and greatly improved but did not eliminate overlap of M0 disease with
      BPH. Reduction of serum PSA to a single volume-corrected variable will allow the
      introduction of practical and optimum protocols for the management of patients
      with prostatic enlargement.

PMID- 1382796
TI  - Limitations of laser treatment for malignant dysphagia.
AB  - Of 86 patients with inoperable malignant dysphagia, 68 (79 per cent) underwent
      successful palliation by endoscopic laser therapy, of whom 24 remained well
      palliated until the time of death. In 18 patients laser treatment was
      unsuccessful and nine of these underwent intubation, eight successfully. After
      successful laser therapy, dysphagia recurred in 44 patients a mean of 7.8 weeks
      later. Of these, 31 received palliation until death by dilatation with or without
      laser therapy, and 13 required intubation. The overall laser-related complication
      rate was 12 per cent with a mortality rate of 4 per cent. The intubation-related
      mortality rate was 9 per cent.

PMID- 1382798
TI  - Direct surface cooling of the exocrine pancreas in the rat.
AB  - A study was carried out to evaluate the effects of direct cooling on the exocrine
      pancreas. Changes in amylase and cathepsin B release, and in the subcellular
      distribution of amylase and cathepsin B were measured after 1, 2 and 3 h of
      direct pancreatic cooling in rats. Cooling for 2 and 3 h caused significant
      hyperamylasaemia and increased pancreatic amylase content, but minimal
      histological change. Furthermore, 3 h of cooling caused marked redistribution of
      cathepsin B activity from the lysosomal fraction to the heavier zymogen fraction,
      and co-localization of lysosomal and digestive enzymes; amylase and cathepsin B
      output into pancreatic juice after caerulein stimulation were also reduced. These
      results show that direct pancreatic cooling impairs exocrine function and
      implicate lysosomal enzymes in the pathogenesis of pancreatic injury, in
      agreement with results from other models of experimental pancreatitis.

PMID- 1382797
TI  - Results of surgical palliation for cancer of the head of the pancreas and
      periampullary region.
AB  - Between 1977 and 1986, 101 patients underwent surgical bypass for periampullary
      carcinoma. The hospital mortality rate was 18 per cent and the morbidity rate 43
      per cent. Mortality was not influenced by the extent of the tumour. Survival
      rates at 1,2 and 3 years were 28, 9 and 4 per cent, respectively. The median
      survival time was 17 months for localized tumours, 10 months for those that had
      invaded surrounding tissues, 6 months in the presence of lymph node involvement
      and 3 months with distant metastasis. The quality of survival was good for most
      patients with localized tumours but poor for those with parenchymal metastasis,
      in whom palliation was transient for 85 per cent and effective for less than half
      of their survival time for 60 per cent. These results suggest that patients with
      distant metastasis but without impending duodenal obstruction should undergo
      palliation by endoscopic or percutaneous routes while those with less advanced
      disease or with duodenal involvement remain candidates for surgical bypass.

PMID- 1382799
TI  - Induction of cobalt accumulation by excitatory amino acids within neurons of the
      hippocampal slice.
AB  - Computer-assisted image analysis was used to establish the dose response of
      excitatory amino acid (EAA) analogs on the induction of cobalt accumulation
      within pyramidal and granule cell neurons in 400 microns slices of gerbil
      hippocampus. Slices were incubated 20 min at 22 degrees C in a solution
      containing 5 mM CoCl2 and 0-1,000 microM EAA analog. The cobalt was visualized by
      development in (NH4)2S, and the slices were digitized for quantitative
      densitometry. Kainic acid (KA) had the largest effect and induced cobalt
      accumulation in the dentate gyrus and CA1, 180% and 150% above control,
      respectively, with an ED50 = 30 microM. alpha-Amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) induced accumulations of cobalt in CA1 and hilar
      neurons 130% above control with an ED50 = 30 microM, but had little effect on
      dentate granule cells. The accumulations induced by KA and AMPA were blocked by 6
      cyano-7-nitroquinoxaline-2,3-dione (CNQX), but not by DL-2-amino-5
      phosphonovaleric acid (AP5) or voltage-dependent calcium channel blockers. N
      Methyl-D-aspartate (NMDA) induced accumulation in the dentate and CA1 150% above
      control in a pattern similar to KA, but with an ED50 of 100 microM. The
      accumulation was blocked by both AP5 and CNQX. These data indicate that cobalt
      permeable, receptor-activated divalent cation channels are differentially
      distributed within the gerbil hippocampus, and have differential sensitivities to
      non-NMDA agonists. The localization of KA-activated, cobalt-permeable channels
      appears to be coincident with the flop form of the AMPA-selective calcium
      permeable glutamate receptor-activated channel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382800
TI  - Decreased neuropeptide-converting enzyme activities in cerebrospinal fluid during
      acute but not chronic phases of collagen induced arthritis in rats.
AB  - We investigated the effects of collagen II-induced arthritis on two cerebrospinal
      fluid (CSF) enzymes converting dynorphin A and substance P (SP), namely dynorphin
      converting enzyme (DCE) and substance P endopeptidase (SPE). The products
      generated by these enzymes are the bioactive fragments Leu-enkephalin-Arg6 and
      substance P, respectively. The strain used (DA rats) is very sensitive towards
      induction of arthritis. The collagen arthritis is a chronic autoimmune arthritis
      induced by native rat collagen type II (CII). Following intradermal injection of
      CII into the tailbase. CSF was sampled on day 21 (acute arthritis) and day 38
      (chronic arthritis). Control rats were untreated because the strain used
      developed an acute and self-limited arthritis (adjuvant arthritis) when
      administered vehicle (i.e. incomplete Freund's adjuvant). The DCE activity was
      significantly lowered in the acute phase of arthritis (P less than 0.05) when
      analysed with two-factor analysis of variance (ANOVA). The enzyme converting SP
      (SPE) also showed a significant decrease in the acute phase of arthritis (P less
      than 0.05). These results demonstrate that both DCE and SPE are affected in the
      acute phase of arthritis. A functional role of these enzymes in processing pain
      related neuropeptides is therefore implicated.

PMID- 1382801
TI  - Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain
      and substantia nigra in relation to nigrostriatal projections and differential
      neuronal susceptibility in Parkinson's disease.
AB  - The anatomy of melanin-containing neurons and other midbrain structures was
      examined by tyrosine hydroxylase (TH), calbindin D28k, and substance P
      immunostaining. Greater than 95% of cells in the substantia nigra pars compacta
      contained melanin, but densely packed cells in a ventral tier had a low content
      of melanin and loosely packed cells in a dorsal tier had a high content of
      melanin. Approximately 60% in the gamma group and 40% in the retrorubral nucleus
      had a low content of melanin. TH immunostaining was moderate in both the ventral
      and dorsal tiers, but more intense in the gamma group and retrorubral nucleus.
      Calbindin D28k was absent from the ventral and dorsal tiers, but present in the
      gamma group and retrorubral nucleus. In the light of primate tracing studies
      these findings suggest that the ventral tier of the pars compacta projects to
      striosomes of the striatum and the dorsal tier, gamma group and retrorubral
      nucleus to the matrix compartment. The ventral tier is more vulnerable than the
      dorsal tier in Parkinson's disease, but the cells contain less melanin. Neither
      tier contains calbindin D28k. This differential vulnerability between the ventral
      and dorsal tiers cannot be explained by melanin or calbindin D28k.

PMID- 1382802
TI  - Localization and retention in vitro of fluorescently labeled aortic baroreceptor
      terminals on neurons from the nucleus tractus solitarius.
AB  - The anterograde fluorescent tracer DiA was used to visualize baroreceptor fibers
      and synaptic terminals both in living and fixed tissue. Baroreceptor fibers
      labeled with DiA terminated as a dense synaptic field in the medial nucleus
      tractus solitarius (NTS), making synaptic contact on the soma, as well as
      processes of neurons that they innervated. A similar distribution and morphology
      was observed in baroreceptor fibers and terminals labeled with horseradish
      peroxidase. DiA also identified baroreceptor terminals and the neurons receiving
      these synaptic contacts in vitro. NTS neurons were dissociated from their
      surrounding tissue and identified by attached baroreceptor terminals that
      retained the fluorescent dye. These results will enable us to study the
      electrophysiological properties of dispersed neurons that receive identified
      baroreceptor synaptic terminals.

PMID- 1382803
TI  - Excitatory amino acid receptor activation produces a selective and long-lasting
      modulation of gene expression in hippocampal neurons.
AB  - Activation of excitatory amino acid (EAA) receptors in cultured hippocampal
      neurons causes down-regulation of the protein ligatin, a receptor for
      phosphoglycoproteins and a marker protein for membrane-vesicle transport systems.
      This reduction occurs at both physiologic and excitotoxic levels of glutamate
      stimulation and is accompanied by a significant decrease in steady state levels
      of ligatin mRNA. Reduction in ligatin mRNA occurs within 60 min and persists 24 h
      later. Steady state levels of mRNAs encoding cyclophilin, an ubiquitous cytosolic
      protein, and neuron specific-enolase (N-SE) are not diminished by glutamate
      receptor activation, demonstrating that down-regulation of ligatin mRNA was not a
      result of general catabolism. Further, this reduction in ligatin mRNA occurred
      without induction of HSP 70. Pharmacological studies using selective antagonists
      and agonists indicate that this down-regulation of ligatin gene expression is
      predominantly mediated by the N-methyl-D-aspartate (NMDA) subclass of EAA
      receptors and that Ca2+ is required. This is the first report that EAA receptor
      activation in hippocampal neurons can pretranslationally down-regulate gene
      expression in a rapid and long-lasting manner under physiologic, as well as
      cytotoxic conditions. The data support the hypothesis that modulation of neuronal
      gene expression may represent a molecular mechanism mediating some of the long
      lasting functional and pathophysiological effects of EAA on cell function.

PMID- 1382804
TI  - Spontaneous and stimulated firing in cultured rat suprachiasmatic neurons.
AB  - Neurons from the suprachiasmatic nucleus (SCN) of the hypothalamus, the site of a
      circadian pacemaker in mammals, were isolated from embryonic rat. After
      mechanical dissociation neurons were brought into culture for 1-2 weeks, using a
      chemically defined medium. Recordings were made from 74 bipolar neurons using two
      different configurations of the patch-clamp technique. During cell attached patch
      recordings, 45% of neurons fired spontaneously. The mean firing rate was 0.7 +/-
      0.6 Hz and the firing pattern was irregular. In whole cell recordings 73% of the
      investigated neurons showed spontaneous activity with an irregular firing
      pattern. The mean spontaneous firing rate with an intracellular Cl- concentration
      of 145 mM was 1.0 +/- 0.6 Hz. The resting membrane potential of the bipolar
      neurons was estimated to be -62 +/- 24 mV. An intracellular Cl- concentration of
      145 mM depolarised the membrane potential. It also increased the probability of
      spontaneous firing. A depolarising current stimulus produced an action potential
      with a threshold voltage of -46 +/- 9 mV. Suprathreshold stimuli resulted in
      repetitive firing with a mean frequency of 12 +/- 4 Hz. The minimum interspike
      interval was 52 +/- 14 ms. All action potentials either occurring spontaneously
      or elicited by current stimuli were abolished by the Na(+)-channel blocker TTX.
      These results indicate that our cultured neurons have some electrophysiological
      properties in common with SCN neurons in brain slices and in vivo.

PMID- 1382805
TI  - Nerve growth factor responsiveness of cultured major pelvic ganglion neurons from
      the adult rat.
AB  - The bladder and other pelvic viscera are innervated in the rat by the major
      pelvic ganglion (MPG), a mixed sympathetic/parasympathetic population of neurons
      that participates in lower urinary pathophysiology. Neurons from the MPG of adult
      females were removed, dissociated and cultured in order to test retention of the
      neuronal phenotype and whether they responded to Nerve Growth Factor (NGF). The
      bladder-specific subset of MPG neurons were distinguished by retrograde labeling
      prior to culture. The adult ganglionic neurons adapted to culture with greater
      than 80% survival in the best cases. The cultured neurons retained excitability,
      as determined by measuring voltage-activated ionic currents. They were positive
      for neuron-specific beta-tubulin and many retained immunoreactivity for
      characteristic peptides and transmitter synthetic enzyme. The proportion of
      neurons in the different categories tested varied somewhat from that in vivo, but
      there was no evidence of selective death of a particular population. The cultured
      MPG neurons were responsive to NGF and anti-NGF antibody. NGF supported neuronal
      survival and expression of tyrosine hydroxylase. Added NGF also affected the
      expression of neuropeptide Y. Hypertrophied neurons from animals with
      experimental bladder outlet obstruction demonstrated increased responsiveness to
      NGF. The data suggest that NGF participates in adult neural plasticity due to
      continued responsiveness to the factor. Furthermore, questions concerning
      regulation of MPG neurons may be addressed in vitro.

PMID- 1382806
TI  - Olfactory bulb transplantation into the olfactory bulb of neonatal rats: a WGA
      HRP study.
AB  - After unilateral bulbectomy in neonatal (P1-P5) rats, autoradiographically
      prelabeled presumptive olfactory bulbs from E15 and E17 embryos were transplanted
      in place of the removed tissue. After 2-7 months, the animals received injections
      of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the piriform
      cortex. Nine of the twenty animals revealed WGA-HRP-positive neurons among
      neurons autoradiographically labeled, providing thus evidence that the axons of
      the output neurons from the homotopically transplanted olfactory bulb reconnect
      with the host piriform cortex.

PMID- 1382807
TI  - Effects of methiothepin on changes in brain serotonin release induced by repeated
      administration of high doses of anorectic serotoninergic drugs.
AB  - We previously observed, using in vivo microdialysis, that the potassium-evoked
      release of frontocortical serotonin (5-HT) is suppressed after rats receive high
      doses (30 mg/kg, i.p., daily for 3 days) of fluoxetine, a selective blocker of 5
      HT reuptake. We now describe similar impairments in 5-HT release after repeated
      administration of two other 5-HT uptake blockers, zimelidine and sertraline (both
      at 20 mg/kg, i.p. for 3 days) as well as after dexfenfluramine (7.5 mg/kg, i.p.
      daily for 3 days), a drug which both releases 5-HT and blocks its reuptake. Doses
      of these indirect serotonin agonists were about 4-6 times the drug's ED50 in
      producing anorexia, a serotonin-related behavior. In addition, methiothepin (20
      microM), a non-selective receptor antagonist, locally perfused through the
      dialysis probe 24 h after the last drug injection, enhanced K(+)-evoked release
      of 5-HT at serotoninergic nerve terminals markedly in control rats and slightly
      in rats treated with high doses of dexfenfluramine or fluoxetine. On the other
      hand, pretreatment with methiothepin (10 mg/kg, i.p.) one hour before each of the
      daily doses of fluoxetine or dexfenfluramine given for 3 days, totally prevented
      the decrease in basal and K(+)-evoked release of 5-HT. Finally, when methiothepin
      was injected systemically the day before the first of 3 daily injections of
      dexfenfluramine, it partially attenuated the long-term depletion of brain 5-HT
      and 5-HIAA levels induced by repeated administration of high doses of
      dexfenfluramine. These data suggest that drugs which bring about the prolonged
      blockade of 5-HT reuptake - such as dexfenfluramine and fluoxetine - can, by
      causing prolonged increases in intrasynaptic 5-HT levels as measured by in vivo
      microdialysis, produce receptor-mediated long-term changes in the processes
      controlling serotonin levels and dynamics.

PMID- 1382808
TI  - Convergence of oral and extraoral information in the superior secondary gustatory
      nucleus of the channel catfish.
AB  - Neurons within the superior secondary gustatory nucleus (nGS) of the channel
      catfish were examined electrophysiologically for responses to mechanical and
      chemical stimulation of neural peripheral receptive fields (RFs). Of the 28
      single units sampled, 18 had mechanosensory RFs on the extraoral epithelium, two
      had RFs within the oropharyngeal cavity, and eight had RFs that included both
      oral and extraoral surfaces. RF sizes varied from approximately 2 cm2 on the
      ipsilateral lips and barbels to the whole body surface, bilaterally. No obvious
      correlation existed between RF pattern and recording location within the nGS.
      Eight of the mechanosensory nGS units also responded to amino acid taste stimuli
      with thresholds from micromolar to millimolar concentrations. The convergence of
      oral and extraoral information within the nGS determined electrophysiologically
      was corroborated anatomically by HRP labeling experiments. Restricted HRP
      injections into each of the primary gustatory nuclei of the medulla, the vagal
      (VL) and facial (FL) lobes, labeled fibers that appeared to terminate diffusely
      throughout the nGS, and injections into different portions of the nGS
      retrogradely labeled cells in both the FL and VL. The present
      electrophysiological and neuroanatomical data distinguish the convergent
      gustatory representation within the nGS of the catfish from the highly specific
      somatotopic and viscerotopic sensory maps previously identified in the FL and VL,
      respectively.

PMID- 1382809
TI  - Effect of neurotransmitters on axoplasmic transport: acetylcholine effect on
      superior cervical ganglion cells.
AB  - The effect of acetylcholine (ACh) on particle movements along axons of cultured
      superior cervical ganglion cells was analyzed with a computer-assisted video
      enhanced differential interference contrast microscope system. ACh suppressed the
      axoplasmic transport reversibly in both anterograde and retrograde directions. A
      muscarinic agonist, arecoline, mimicked the ACh effect, but nicotine did not. An
      experiment with the Ca(2+)-indicator dye, fura-2, revealed that ACh suppressed
      the transport without any change of intracellular Ca2+ concentration. ACh also
      suppressed the axoplasmic transport in Ca(2+)-free medium. Islet-activating
      protein (IAP), pertussis toxin, blocked the ACh effect. These results indicate
      that ACh activates muscarinic receptors and suppresses fast axoplasmic transport
      through the activation of IAP-sensitive GTP-binding protein, irrespective of Ca2+
      ions.

PMID- 1382810
TI  - Barbiturate tolerance: effects on GABA-operated chloride channel function.
AB  - Male ICR mice were fed powdered laboratory chow containing phenobarbital for 7
      days to induce tolerance. Mice were sacrificed and brains assayed for changes in
      GABA-mediated chloride flux into brain membrane vesicles (microsacs).
      Concentration-dependent stimulation of chloride flux by GABA alone was not
      affected by the development of tolerance to phenobarbital. Phenobarbital
      potentiation of GABA-mediated chloride flux was significantly attenuated in the
      membranes prepared from phenobarbital-tolerant mice compared with those from pair
      fed control mice. Similarly, stimulation of GABA-mediated flux by the
      benzodiazepine, flunitrazepam was also depressed in membranes from tolerant mice.
      However, the ability of ethanol and the benzodiazepine inverse agonist FG-7142 to
      modulate GABA-gated chloride flux was not affected by the development of
      phenobarbital tolerance. No significant changes in saturation [3H]diazepam
      binding parameters were observed. These findings suggest that there is a degree
      of cross-tolerance between phenobarbital and benzodiazepine agonist at the level
      of the GABA-operated chloride channel. Furthermore, although some reports have
      demonstrated behavioral cross-tolerance between ethanol and barbiturates, the
      present data suggest different mechanisms of tolerance development for these
      intoxicants at the level of the GABAA receptor chloride channel complex.

PMID- 1382811
TI  - Time course of serotonergic afferent plasticity within rat spinal trigeminal
      nucleus following infraorbital nerve transection.
AB  - High-performance liquid chromatography with electrochemical detection (HPLC-ED)
      and immunocytochemistry were used to examine the time course of serotonergic
      afferent plasticity within trigeminal subnucleus interpolaris (SpVi) following
      infraorbital nerve (ION) transection in adult rats. Biochemical analysis was also
      performed in trigeminal subnucleus caudalis (SpVc) to examine the possibility of
      transient lesion-induced changes in this region. No significant changes in
      serotonin (5-HT) or 5-hydroxyindoleacetic acid (5-HIAA) concentration, or in
      density of 5-HT-immunoreactive (5-HTIR) axonal varicosities were observed in
      either subnucleus on the lesioned side, up to 51 days following ION cut. However,
      at 76-79 days post-lesion, a significant increase in 5-HT concentration was again
      demonstrated within SpVi.

PMID- 1382812
TI  - Excitotoxic lesions of the pedunculopontine tegmental nucleus of the rat. I.
      Comparison of the effects of various excitotoxins, with particular reference to
      the loss of immunohistochemically identified cholinergic neurons.
AB  - The pedunculopontine tegmental nucleus (PPTg) has been shown to have cholinergic
      connections with the thalamus and basal ganglia. The ability of various doses of
      the excitotoxins (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
      (AMPA), folate, ibotenate, kainate, N-methyl-D-aspartate (NMDA), quinolinate and
      quisqualate to make lesions in the PPTg was examined, with particular reference
      to their ability to destroy cholinergic neurons identified using choline
      acetyltransferase (ChAT) immunohistochemistry. All of the toxins induced
      convulsive activity on recovery from surgical anesthesia and all except folate
      made lesions in the PPTg and surrounding structures. The size of the lesions was
      computed following examination of Cresyl violet stained sections. The largest
      lesions were made by kainate = AMPA greater than NMDA = ibotenate greater than
      quisqualate = quinolinate. All of the toxins destroyed cholinergic neurons,
      higher doses producing greater loss than lower. The ratio of cholinergic cell
      loss to general neuronal loss (assessed by Cresyl violet staining) was also
      computed, revealing marked differences between the toxins. Statistical analysis
      showed that there were significant differences between excitotoxins in terms of
      this ratio, but these were accounted for by the low dose of quinolinate (24 nmol)
      producing a significantly greater ratio of damage (12.18:1) than every other
      toxin. (Next highest ratio: quisqualate 60 nmol, 6.22:1.) Between the other
      toxins (kainate, AMPA, ibotenate, quisqualate, NMDA and the high dose of
      quinolinate) there were no statistically significant differences. Intense calcium
      deposits (stained by Alizarin red) were found frequently and often defined the
      borders of the lesion. Tyrosine hydroxylase immunohistochemistry revealed axons
      running below and into the area of lesioned tissue suggesting strongly that
      fibers were undamaged by the lesions. We conclude that in the PPTg, different
      excitotoxins make discriminably different lesions, both quantitatively and
      qualitatively. Unlike excitotoxic lesions in the basal forebrain quinolinate, not
      quisqualate, made the most selective lesions of cholinergic neurons and, unlike
      excitotoxic lesions in the septal nuclei, non-myelinated fibers were spared by
      ibotenate. The implications of these data for research into brainstem mechanisms
      of Parkinson's disease are discussed.

PMID- 1382813
TI  - Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane
      (para-methoxymethamphetamine, PMMA).
AB  - These studies assessed the neurotoxic potential of N-methyl-1-(4-methoxyphenyl)-2
      aminopropane (para-methoxymethamphetamine; PMMA), an amphetamine analog that has
      surfaced in the illicit drug market. Repeated subcutaneous injections of PMMA
      caused lasting, dose-related reductions in regional brain concentrations of
      serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), and in the density of
      [3H]paroxetine-labelled 5-HT uptake sites. Comparison of the neurotoxic potential
      of PMMA to that of para-methoxyamphetamine (PMA) and 3,4-methyl
      enedioxymethamphetamine (MDMA) showed that equivalent doses of PMMA and PMA (80
      mg/kg) produced comparable depletions of 5-HT, but that these depletions were not
      as pronounced as those induced by a lower dose of MDMA (20 mg/kg). Striatal DA
      was not affected on a long-term basis by any of the ring-substituted amphetamines
      evaluated in this study. These data suggest that PMMA, like PMA and MDMA,
      produces long-term (possibly neurotoxic) effects on brain serotonin neurons, but
      that PMMA is less potent than MDMA as a 5-HT neurotoxin. Further, they raise
      concern over the illicit use of PMMA since humans could be more sensitive than
      rodents to the 5-HT neurotoxic effects of PMMA and related drugs.

PMID- 1382814
TI  - Wallerian degeneration in the optic nerve of the wabbler-lethal (wl/wl) mouse.
AB  - Optic nerve pathology was studied in C57BL/6J wabbler-lethal (wl/wl) and control
      (+/+) mice at postnatal age of 4 weeks (P28). Qualitative light and
      ultrastructural pathology in wl/wl animals conformed to the criteria of primary
      axonal (Wallerian) degeneration. Most optic nerve axons in mutant animals
      appeared normal, as did oligodendroglia, the degree of myelination, the integrity
      and maturity of vascular elements, astroglia, and most myelin. Still,
      degenerating axons surrounded by somewhat normal myelin and axons with thickened
      myelin sheaths were prevalent in wl/wl mice. Dysmyelination or hypomyelination
      was not evident. At P28, pathology appeared more prominent in large diameter
      fibers. In the optic nerve of wl/wl mice, axonal degeneration preceded myelin
      disruption, adding this nerve to other previously reported systems undergoing
      Wallerian degeneration in this mutant.

PMID- 1382815
TI  - Regional differences in chronic neuroleptic effects on extracellular dopamine
      activity.
AB  - The extracellular levels of dopamine (DA) and DA metabolites in the caudate
      putamen (CPu) and the nucleus accumbens (NA) of rats following administration of
      haloperidol (HAL) decanoate and fluphenazine (FLU) decanoate for 8 months were
      assessed using intracranial microdialysis 1 month after final injection. Both HAL
      and FLU-treated animals showed persisting plasma neuroleptic levels at time of
      sacrifice. Extracellular basal levels of homovanillic acid (HVA) in the CPu were
      significantly elevated in the FLU-treated animals, while basal levels of 3,4
      dihydroxyphenylacetic acid (DOPAC) in the CPu were significantly elevated in the
      HAL-treated animals. Basal levels of DA and the serotonin metabolite, 5
      hydroxyindoleacetic acid (5HIAA) in the CPu were not significantly different
      between groups. No significant between-group differences were found for basal
      levels of any of the analytes in the NA. Neuroleptic-treated animals showed an
      enhanced response to direct infusion through the dialysis probe of amphetamine (1
      microM) and nomifensine (10 microM) in the CPu but not the NA. These results
      suggest that chronic neuroleptic treatment produces enhanced extracellular DA
      activity in nigrostriatal, but not mesolimbic DA pathways.

PMID- 1382816
TI  - Enhancement of slow wave sleep parallel to the satiating effect of acidic
      fibroblast growth factor in rats.
AB  - Male Wistar rats bearing both chronic cortical electrodes and ICV guide cannula
      were used. Acidic fibroblast growth factor (aFGF) or vehicle was injected in the
      lateral ventricle (20, 40, and 80 ng) while EEG and feeding patterns (via
      microbalance and a computerized monitor) were recorded. Forty and 80, but not 20,
      ng of aFGF brought about a significant reduction of feeding during 3 h and a
      dramatic increase of slow wave sleep during 6 h postinjection. Paradoxical sleep
      remained unchanged. Rectal temperature did not change. These concomitant effects
      of a single injection of aFGF on feeding and particularly on sleep are similar to
      the effect of a large meal on the same behavioral parameters.

PMID- 1382817
TI  - Childhood trauma and multiple personality disorder: the case of a 9-year-old
      girl.
AB  - This paper reports the case of a 9-year-old girl, evaluated and diagnosed with
      multiple personality disorder over a 6 month period. Included is a detailed
      description of the child's presentation with historical and developmental data. A
      discussion of the dynamic and predisposing features of the case with references
      to current literature follows, along with treatment perspectives.

PMID- 1382818
TI  - [Characteristics of monoclonal antibodies against chorionic gonadotropin
      receptor].
AB  - We reported the production of monoclonal antibodies (McAb) against chorionic
      gonadotropin (CG) receptor by fusing spleen cells of BALB/c mice immunized with
      purified pseudomonas maltophilia CG receptor with mouse myeloma line (SP 2/0).
      Four hybridoma cell lines secreting CG receptor McAbs were obtained (ED 490, DG
      390, AB 890, GE 590). GE 590 is IgG 1; ED 490, DG 390, AB 890 are IgG2b. I125-HCG
      and ED 490, DG 390. AB 890 recognized CG receptor different antigenic
      determinant. Increased concentrations of GE 590 were in inverse proportion to the
      amount of I125-HCG binding to human ovarian tissues showing that normal ovarian
      tissues and ovarian malignant tumors have different HCG receptor antigenic
      determinant. This study indicated that these McAbs may be useful in studying the
      structure of CG receptor and in providing a valuable evidence for early diagnosis
      and treatment of ovarian malignant tumors.

PMID- 1382819
TI  - Heterogeneity of IgE antibody response to reactive dye in sera from four
      different sensitized workers.
AB  - We studied RAST and RAST inhibition tests to black GR, the most frequent
      sensitizer among several reactive dyes in our previous study, in order to
      evaluate the specificity of IgE antibodies to hapten or new antigenic
      determinants and the crossreactivity between two reactive dyes, black GR and
      orange 3R, in sera from four different sensitized workers. RAST inhibition
      studies with black GR-human serum albumin (HSA) conjugate discs demonstrated that
      black GR-HSA conjugates were the most effective inhibitors. Orange 3R-HSA
      conjugates, unconjugated forms of black GR and orange 3R were weak inhibitors in
      two patients and non-inhibitory in one patient, whereas they caused strong dose
      dependent inhibitions in one patient. These results suggested that the IgE
      response to black GR-HSA conjugates might be heterogenous and the crossreactivity
      between two reactive dyes differed from one patient to another.

PMID- 1382820
TI  - Variability of crossreactivity of IgE antibodies to group I and V allergens in
      eight grass pollen species.
AB  - Crossreactivity to Dactylis glomerata, Festuca rubra, Phleum pratense,
      Anthoxanthum odoratum, Secale cereale, Zea mays, and Phragmites communis of IgE
      antibodies against Lol p I or Lol p V was investigated by means of RAST
      inhibition. Within a group of sera the degree of crossreactivity was demonstrated
      to be highly variable. Individual sera were not always equally crossreactive to
      all pollen species. A high degree of crossreactivity for Group I allergens did
      not necessarily implicate the same for Group V. Group I and Group V
      representatives were found to be present in all eight species. It was
      demonstrated that within this group of grass species significant quantitative and
      qualitative differences exist, with respect to Group I and Group V allergens.
      Species with a low phylogenetic affinity to Lolium perenne, like Zea mays and
      Phragmites communis showed a very low degree of reactivity, even when measured
      with the most crossreactive sera. A higher taxonomic relationship however, did
      not always implicate a closer antigenic resemblance. Antigenically both allergens
      from Zea mays are more similar to Lol p I and Lol p V, than the analogues in
      Secale cereale.

PMID- 1382822
TI  - Characterization of an O-antigen bacteriophage from Aeromonas hydrophila.
AB  - A unique bacteriophage of Aeromonas hydrophila serotype O:34 was isolated,
      purified, and characterized. The bacterial surface receptor was shown to be the O
      antigen polysaccharide component of lipopolysaccharide specific to serotype O:34,
      which was chemically characterized. The high molecular weight lipopolysaccharide
      fraction (a fraction enriched in O antigen) was fully able to inactivate
      bacteriophage PM1. Phage-resistant mutants of A. hydrophila O:34 were isolated
      and found to be specifically devoid of lipopolysaccharide O antigen. No other
      cell-surface molecules were involved in phage binding. The host range of
      bacteriophage PM1 was found to be very narrow, producing plaques only on A.
      hydrophila strains from serotype O:34.

PMID- 1382821
TI  - Common epitopes of mammalian amelogenins at the C-terminus and possible
      functional roles of the corresponding domain in enamel mineralization.
AB  - The present studies were undertaken to investigate the presence of common
      epitopes of mammalian amelogenins at the C-terminus and the possible functional
      importance of the conserved C-terminal domain in enamel mineralization during
      mammalian amelogenesis. Enamel proteins, including the intact amelogenins and
      their degraded polypeptides, were isolated from the secretory enamel of pig, cow,
      rat, and rabbit incisors. Rabbit and rat antipeptide sera, as well as rat anti-25
      kD and 20 kD pig amelogenin sera, were used to identify the amelogenins among the
      isolated matrix proteins of each of the animal species. The antipeptide sera were
      developed previously (Aoba et al. [19]) using as immunogens the two synthetic
      peptides, C13 and C25, which correspond to the last 12 (plus Cys for KLH
      conjugation) and 25 amino acid residues of pig intact amelogenin, respectively.
      Reactivity of the enamel proteins with each antiserum was examined by Western
      blot analysis. The results of immunoblotting showed that a few enamel matrix
      proteins in each of the mammalian species were recognized by the anti-C13 serum,
      specifically, pig amelogenin at 25 kD (and trace components at 27, 22, and 18
      kD), cow amelogenin at 28 kD (trace components at 26, 22, 19, and 14 kD), rat
      amelogenins at 28 and 26 kD (and a trace component at 20 kD), and rabbit
      amelogenins at 24 and 21 kD (and a trace at 13 kD). The anti-C25 serum reacted
      additionally with pig amelogenin at 23 kD, cow amelogenin at 27 kD (a major
      matrix constituent), and rabbit protein at 19 kD.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382823
TI  - Construction of the physical maps of Mycoplasma hyopneumoniae and Mycoplasma
      flocculare and the location of rRNA genes on these maps.
AB  - The genomes of Mycoplasma flocculare and Mycoplasma hyopneumoniae, two
      mycoplasmas of the porcine respiratory system, were studied. Based upon antigenic
      cross-reactivity and DNA-DNA hybridization, these species have given indication
      of a close genetic relationship. By using field-inversion gel electrophoresis and
      employing the restriction digest fragments obtained from the gels as the probes,
      physical maps of the genomes of the two species were constructed. Mycoplasma
      hyopneumoniae is similar to M. flocculare in having a single set of rRNA genes
      and the 5S-rRNA gene is separated from the 16S and 23S rRNA genes. Based upon the
      location of the rRNA genes on the physical maps in both species, the distance
      between the 5S and the 16S and 23S rRNA genes is at least 150 kbp. Thus, there is
      further evidence for the close relationship between these organisms.

PMID- 1382824
TI  - Escherichia coli serotyping and disease in man and animals.
AB  - Serotyping of Escherichia coli is useful, but complex, with 173 O antigens, 80 K
      antigens, and 56 H antigens, which can all be subdivided into partial antigens.
      The O, K, and H antigens can be found in nature in many of the possible
      combinations. The final number of E. coli serotypes is very high, 50,000-100,000
      or more. The number of frequent pathogenic serotypes is, however, limited. Two
      main groups of such frequent serotypes are (i) serotypes from diarrhoeal disease
      and (ii) serotypes from extraintestinal disease. Serotypes from diarrhoeal
      diseases are mostly species specific, and could at present be used as
      epidemiological markers for bacterial clones equipped with special virulence
      markers, such as toxins and adhesins. Their O-antigen lipopolysaccharides may be
      regarded as virulence factors. These strains are not inhabitants of the normal
      intestine. Serotypes from extraintestinal diseases constitute a different set of
      clones, which are good colonizers of the intestinal tract, that under certain
      conditions succeed in invading host tissues. They are characterized by virulence
      factors different from those found in strains from diarrhoeal disease. Thus, the
      two groups of pathogenic E. coli are both composed of a limited number of clones
      for which the O:K:H serotypes are excellent, although not faultless, markers.

PMID- 1382825
TI  - Pathogenicity and molecular genetics of O-specific side-chain lipopolysaccharides
      of Escherichia coli.
AB  - Lipopolysaccharide (LPS), a glycolipid molecule found on the outer leaflet of
      outer membranes of gram-negative bacteria, consists of three moieties: lipid A,
      core oligosaccharide, and the O-specific polysaccharide chain. The O-specific
      side chain, which extends to the extracellular milieu, plays an important role in
      pathogenicity, especially during the initial stages of infection, because of its
      ability to interact with serum complement. In recent years, several laboratories
      have used recombinant DNA tools to determine, at the molecular level, the
      organization, expression, and regulation of genes involved in LPS biosynthesis in
      Salmonella and Escherichia coli. An increased understanding of the molecular
      aspects of the O-specific side-chain genes will shed light on the intimate
      details related with the formation of the O-specific side chain, its assembly
      onto the lipid A--core, and the translocation and insertion of the complete LPS
      molecule into the outer membrane. It will also contribute to the understanding of
      the evolution of these genes and the correlation of chemical diversity of O
      specific side chains with the genetic diversity of O-specific side-chain genes.
      In addition, since the O-specific side chains are involved in the pathogenicity
      of medically important gram-negative bacteria, a basic understanding of the
      regulation and expression of O-specific side chain LPS genes will contribute to
      the field of molecular pathogenesis. This article provides an overview of the
      role of O-specific side chains in septicemic infections and also discusses the
      current status of molecular genetic studies on O-specific side-chain genes from
      E. coli.

PMID- 1382826
TI  - Thymic hyperplasia with hemorrhage simulating recurrent Hodgkin disease after
      chemotherapy-induced complete remission.
AB  - BACKGROUND: Thymic hyperplasia after successful treatment of malignant disease is
      a well-documented phenomenon, particularly in younger patients with testicular
      carcinoma. However, it has been reported only sporadically in association with
      Hodgkin disease. The authors report the first instance of an adult with nodular
      sclerosing Hodgkin disease who had thymic hyperplasia develop after clinical and
      radiographic complete remission (CR) with chemotherapy alone. METHODS: In
      addition to the current case, 20 other instances of thymic hyperplasia have been
      culled from the literature and analyzed. RESULTS: The median age of these 21
      patients was 23 years of age (range, 8-40 years of age). Thymic hyperplasia was
      noted after treatment was initiated or completed in all but two patients; and all
      did well, with one exception: a 17 year-old boy who was inadvertently treated for
      relapsed Hodgkin disease and who died of fibrinous pneumonitis and nocardia, with
      pathologic CR noted at autopsy. CONCLUSIONS: Thymic hyperplasia in association
      with Hodgkin disease appears to be a favorable prognostic phenomenon, restricted
      to younger patients in the first modal peak of Hodgkin incidence. Prospective
      studies have yet to be performed.

PMID- 1382827
TI  - Successful treatment of a primary endodermal sinus tumor of the liver.
AB  - A 27-year-old woman had a large hepatic tumor and a markedly increased serum
      alpha-fetoprotein (AFP) level. A diagnosis of endodermal sinus tumor was made
      after a needle biopsy was performed on the liver. Clinical and radiologic
      examinations did not show an alternative primary site. Treatment with cisplatin,
      etoposide, and bleomycin was started, but, after three cycles, was changed to
      cisplatin, vincristine, methotrexate, bleomycin, dactinomycin, cyclophosphamide,
      and etoposide because the serum AFP level was decreasing too slowly. After
      additional chemotherapy was given, the patient was well but had an increased AFP
      level and a large residual mass in the liver. A right hemihepatectomy was
      performed, but no viable tumor was present. The patient is alive and disease-free
      5 years later. Thus, AFP levels may be misleading in the presence of large
      necrotic tumors. The authors stress the need to make a diagnosis of these rare
      tumors early because aggressive treatment with combination chemotherapy may
      result in cure.

PMID- 1382828
TI  - Prognostic significance of changes in prostate-specific markers after endocrine
      treatment of stage D2 prostatic cancer.
AB  - BACKGROUND: The prognostic value was determined of prostate-specific antigen
      (PSA) and prostatic acid phosphatase (PAP) measured before and after endocrine
      treatment in 57 patients with newly diagnosed Stage D2 prostatic cancer. METHODS:
      Therapy included orchiectomy or administration of luteinizing hormone releasing
      hormone analogues or an antiandrogen. RESULTS: The absolute pretreatment PSA
      (elevated in 100% of patients) but not PAP (abnormal in 93%) predicted disease
      progression (P < 0.0011), i.e., a poor response to therapy. Fifty-three patients
      responded to androgen deprivation with a decrease in PSA level. This declined to
      normal at 3 and 6 months in 25% of patients. Forty-nine percent had a greater
      than 90% decrease in their PSA level. By 1 year, 58% of patients had progressive
      disease. Both the nadir PSA level and the percent decline from the pretreatment
      level at 3 and 6 months predicted the progression-free interval (P < 0.001).
      Patients with a 90% or greater decline in PSA had a prolonged progression-free
      survival. Serial PAP levels were similarly prognostic. CONCLUSION: It was
      concluded that PSA was better than PAP in evaluating patients before and after
      androgen-deprivation therapy. The nadir level of both markers was an important
      tool to predict progression-free survival in patients with metastatic prostatic
      cancer.

PMID- 1382829
TI  - A phase II study of recombinant human alpha-interferon in advanced hormone
      refractory prostate cancer.
AB  - To determine the efficacy of recombinant human leukocyte alpha-interferon (IFL
      RA) in advanced hormone-refractory prostate cancer, the authors treated 40
      patients with IFL-RA administered intramuscularly at a dose of 10 x 10(6) U/m2
      three times weekly. Toxicity was substantial and necessitated at least a 50% dose
      reduction in all but five patients during the first 1-2 months of therapy. No
      responses were observed in patients with bone metastases, but complete and
      partial regression of nodal disease were observed in two patients with
      extraosseous disease (overall response rate, 5%; 95% confidence interval, 0.64
      17.75%). The authors conclude that IFL-RA cannot be recommended at this dose and
      schedule in patients with advanced prostate cancer, but additional study of its
      use in patients with nodal disease may be warranted.

PMID- 1382830
TI  - Multiple cancers in the prostate. Morphologic features of clinically recognized
      versus incidental tumors.
AB  - Multiple independent tumors were identified in specimens from 117 of 234
      prostatectomies for clinical adenocarcinoma; there were 266 incidental cancers in
      these 117 prostates. The clinically detected carcinoma was the largest (or only)
      tumor in all 202 Stage B cases. However, among 32 Stage A cases (detection by
      transurethral resection), there were 8 prostates in which an incidental tumor was
      larger than the clinically manifest cancer. These were all small tumors except
      for two incidental cancers with a volume greater than 2cm3; roughly 80% of
      incidental carcinomas were smaller than 0.5 cm3, whereas fewer than 20% of
      manifest tumors were smaller than 0.5 cm3. Comparison with a series of cancers
      found incidentally at cystoprostatectomy for bladder cancer showed the same
      volume distribution as incidental (smaller) carcinomas in patients with prostate
      cancer. This distribution was thought to reflect the volume distribution of
      prostate cancer in the general population older than 50 years of age. It was
      concluded that additional incidental tumors are common in patients with prostate
      cancer, but their sum of volumes is seldom as large as the clinical cancer
      volume.

PMID- 1382831
TI  - An immunohistochemical study of epithelial membrane antigen, cytokeratin, and
      vimentin in papillary thyroid carcinoma. Recognition of lethal and favorable
      prognostic types.
AB  - METHODS: Immunoreactivity for epithelial membrane antigen (EMA), cytokeratin, and
      vimentin was investigated in 15 papillary thyroid carcinomas (PTC) with distant
      metastases, 25 PTC without distant metastases, and 34 occult PTC without distant
      metastases that were found incidentally at autopsy. RESULTS: More than 50% of the
      tumor cells were positive for EMA in 7 (47%) of 15 PTC with distant metastases, 0
      (0%) of 25 PTC without distant metastases, and 1 (3%) of 34 occult PTC. The
      incidence of EMA positivity in PTC with distant metastases was significantly
      different from that of both PTC without distant metastases and occult PTC (P <
      0.001). Cytokeratin reactivity was similar in the three groups, and almost all
      PTC stained strongly for cytokeratin. Concerning vimentin positivity, there were
      no significant differences in three groups; however, PTC with distant metastases
      tended to stain more weakly or focally than PTC without distant metastases or
      occult PTC. CONCLUSIONS: These results suggest that EMA reactivity may be a
      useful factor for anticipating the individual risk of distant metastasis or death
      from PTC at the time of initial surgical treatment.

PMID- 1382832
TI  - Surgical resection of solitary metastases after chemotherapy in patients with
      nonseminomatous germ cell tumors and elevated serum tumor markers.
AB  - BACKGROUND: Chemorefractory metastatic germ cell tumors and elevated tumor
      markers generally indicate inoperable disease. METHODS: Solitary metastases were
      resected in 15 patients who had a nonseminomatous germ cell tumor and an elevated
      alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) serum level
      after treatment with cisplatin-based chemotherapy. Patients underwent resection
      for a residual mass after chemotherapy or for a new solitary metastasis after
      achieving a complete response (CR) to salvage chemotherapy. RESULTS: Seven
      patients were disease-free after surgical resection alone. All five patients with
      an elevated HCG level had a relapse after surgery compared with 3 of 10 patients
      with only an elevated AFP level. Only 4 of 10 patients with a retroperitoneal
      metastasis had a relapse after surgery compared with 4 of 5 patients with
      visceral disease. Eleven of 15 patients overall were disease-free after surgery
      and subsequent chemotherapy after a relapse. CONCLUSIONS: Surgical resection of a
      solitary metastasis despite elevated serum tumor markers should be considered in
      patients who have not had a durable CR to cisplatin-based chemotherapy.

PMID- 1382833
TI  - Serial monitoring of patients with prostate cancer treated with anti-androgen
      therapy.

PMID- 1382834
TI  - Co-ordinate expression of c-fos, p53 and cytokeratin genes during the alteration
      of growth of human hepatoma cells. mRNA levels measured by reverse transcription
      and polymerase chain reaction.
AB  - Teleocidin, a tumor promoter, inhibited the proliferation, enhanced cytokeratin
      assembly and increased the type III procollagen production of PLC/PRF/5 hepatoma
      cells. Teleocidin transiently increased the levels of c-fos and p53 mRNAs
      measured by reverse transcription and polymerase chain reaction. This was
      followed by a reduction of c-myc mRNA and an increase of cytokeratin mRNA. The
      level of p120 mRNA was not remarkably altered. Sequential alterations of the
      expression of c-fos, p53, c-myc and cytokeratin genes induced by teleocidin may
      be responsible for the morphological and functional changes of hepatoma cells
      induced by this tumor promoter.

PMID- 1382835
TI  - Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro.
AB  - Chrysotile asbestos stimulates T lymphocyte subsets. Cell surface CD4 or CD45RA
      expression in peripheral blood mononuclear cells (PBMC) was downregulated after
      incubation with chrysotile asbestos in vitro temporarily. The percentage of
      CD4+CD45RA+ cells and mean fluorescence intensity in CD4 or CD45RA decreased
      after incubation with asbestos and returned to the original level after 24 h of
      incubation, which suggests that chrysotile asbestos activates CD4+CD45RA+ cells.
      No change was observed in CD29 expression. An increased percentage of IL-2R
      positive cells and an elevated intracellular Ca++ level were also indicative of
      the activation of PBMC by chrysotile asbestos.

PMID- 1382836
TI  - P-glycoprotein expression during tumor progression in the rat liver.
AB  - P-Glycoprotein (Pgp) has been shown to mediate multidrug resistance in tumor cell
      lines. Overexpression of Pgp has been detected in clinical cancer samples of many
      histological types. The basis and biological significance of such increases in
      Pgp expression are not well understood. In this study, the expression of Pgp
      during stepwise progression to rat liver cancer was examined to investigate the
      possible role of Pgp in carcinogenesis. An immunohistochemical technique was used
      to detect Pgp at the single-cell level, in a large number of liver nodules,
      hepatocellular carcinoma, and in distant metastases of the carcinomas. The
      results showed that distinct changes in Pgp expression occurred during stepwise
      liver carcinogenesis and that these changes were closely associated with the
      microscopic anatomy of the lesions. In contrast to gamma-glutamyl transpeptidase
      and glutathione S-transferase-7.7, whose expression appeared to correlate with
      the early steps of liver carcinogenesis, Pgp expression was higher in the large
      hyperplastic nodules and in hepatocellular carcinomas than in the early
      microscopic lesions. A particularly striking finding was the consistent
      expression of Pgp in the lung metastases. These findings suggested that Pgp was
      associated with a more progressed malignant phenotype in liver carcinogenesis.

PMID- 1382837
TI  - Loss of epithelial markers and acquisition of vimentin expression in adriamycin-
      and vinblastine-resistant human breast cancer cell lines.
AB  - We have previously observed that breast cancer cell lines could exhibit either
      epithelial or fibroblastic phenotypes as reflected by their morphologies and
      intermediate filament protein expression (C. L. Sommers, D. Walker-Jones, S. E.
      Heckford, P. Worland, E. Valverius, R. Clark, M. Stampfer, and E. P. Gelmann,
      Cancer Res., 49:4258-4263, 1989). Fibroblastoid, vimentin-expressing breast
      cancer cell lines are more invasive in vitro and in vivo (E. W. Thompson, S.
      Paik, N. Brunner, C. L. Sommers, G. Zugmaier, R. Clarke, T. B. Shima, J. Torri,
      S. Donahue, M. E. Lippman, G. R. Martin, and R. B. Dickson, J. Cell. Physiol.,
      150: 534-544, 1992). We hypothesized that a breast cancer cell with an epithelial
      phenotype could undergo a transition to a fibroblastic phenotype, possibly
      resulting in more invasive capacity. We now show that two Adriamycin-resistant
      MCF-7 cell lines and a vinblastine-resistant ZR-75-B cell line have undergone
      such a transition. Adriamycin-resistant MCF-7 cells express vimentin, have
      diminished keratin 19 expression, have lost cell adhesion molecule uvomorulin
      expression, and have reduced formation of desmosomes and tight junctions as
      determined by reduced immunodetection of their components desmoplakins I and II
      and zonula occludens (ZO)-1. Other MCF-7 cell lines selected for resistance to
      vinblastine and to Adriamycin and verapamil did not have these characteristics,
      indicating that drug selection does not invariably cause these phenotypic
      changes. In addition, to determine if vimentin expression in MCF-7 cells alone
      could manifest a fibroblastic phenotype, we transfected the full-length human
      vimentin complementary DNA into MCF-7 cells. Although vimentin expression was
      achieved in MCF-7 cells, it did not affect the phenotype of the cells in terms of
      the distribution of keratins, desmoplakins I and II, ZO-1, or uvomorulin or in
      terms of in vitro invasiveness. We conclude that vimentin expression is a marker
      for a fibroblastic and invasive phenotype in breast cancer cells but does not by
      itself give rise to this phenotype.

PMID- 1382838
TI  - Insulin-like growth factor binding proteins in human breast cancer tissue.
AB  - Breast tumor cell lines have been shown to secrete at least five distinct insulin
      like growth factor (IGF) binding proteins (IGFBP), the secretion being related to
      the estrogen receptor (ER) content. In this study we investigated IGFBP mRNA
      expression and IGFBP content in relation to ER content in human breast tumors.
      Tissue specimens from 47 breast cancers were studied. In five cases the adjacent
      histologically normal tissue was also analyzed. IGFBP content in tissue
      homogenates was studied by Western ligand blot analysis, using [125I] IGF-I as a
      label, and IGFBP mRNA expression by reverse transcriptase polymerase chain
      reaction. The results show that human breast tumors express mRNAs encoding IGFBP
      1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-5. The pattern of IGFBPs in different
      tumors varies. No correlation exists between ER content and IGFBPs with molecular
      weights 24,000 Mr, 28,000 Mr, 34,000 Mr or 43,000 Mr, whereas the 49,000 Mr IGFBP
      was more abundant in ER negative tumors (P less than 0.05). The IGFBP content was
      significantly (P less than 0.05) higher in five tumors than in their adjacent
      normal tissues suggesting that increased content of IGFBPs is a feature typically
      associated with the malignant transformation of breast tissue.

PMID- 1382839
TI  - Product of the Steel locus can replace leukemic cell interaction.
AB  - Mutations in the Steel locus, encoding a growth factor (Steel factor or SF) or c
      kit, the gene encoding its receptor, result in severe anemia in the mouse. In the
      present study, we have addressed the mechanism of synergistic growth activation,
      at the cellular level, by SF and GM-CSF using the blast cells of acute
      myeloblastic leukemia (AML blasts). Our data indicate that SF drastically
      alleviates the requirement in cell interaction for blast colony formation in most
      of the samples tested. Analysis of cultures performed in the presence of SF and
      GM-CSF at different cell concentrations, ranging from 1,000 to 20,000 cells,
      suggested a single limiting element, i.e., the blast clonogenic cell, while 2 or
      more limiting elements were found in cultures stimulated with GM-CSF alone,
      suggesting interacting cell populations. The presence of membrane-bound SF was
      detected by immunofluorescence, suggesting the possibility that secreted or
      membrane-bound SF may, at least in part, contribute to the density-dependent
      growth of AML blasts. In all samples tested, SF appears to increase the
      responsiveness of AML blasts to GM-CSF, as demonstrated by a 3-fold decrease of
      GM-CSF half efficient concentration on addition of SF to the cultures. Exposure
      of AML blasts to SF did not affect GM-CSF receptor expression, suggesting that
      this increase in GM-CSF responsiveness is likely to occur at the postreceptor
      level. Interestingly, 2 of 15 AML samples surveyed did not respond to SF, and
      were both of the myelomonocytic or monocytic subtype, classified as M4 and M5,
      respectively.

PMID- 1382840
TI  - Flow cytometric detection of drugs altering the DNA methylation pattern.
AB  - We have developed a model system for assessing the demethylating potential of
      external agents. Disruption in the DNA methylation pattern was evaluated at the
      translational level of the Escherichia coli beta-galactosidase coding gene
      (lacZ). We have constructed a clonal cell line (A4/4 cells) derived from the
      adenovirus-transformed human embryonic kidney 293 strain. The A4/4 cells contain
      the E. coli lacZ gene under the control of the mouse metallothionein 1 promoter
      which is down-regulated by a natural DNA methylation pattern. Furthermore, the
      lacZ transcription is also regulated by the E. coli lac operator/repressor system
      and by mouse metallothionein 1 metal responsiveness offering a wide range in lacZ
      expression. In this system, the beta-galactosidase activity was only recovered in
      the presence of a demethylating agent such as 5-azacytidine. The demethylating
      potential of 5-azacytidine, 5-aza 2'-deoxycytidine and sodium butyrate was
      rapidly assessed by a flow cytometric method using fluorescein di-beta-D
      galactopyranoside as a fluorescent probe. A tremendous induction of lacZ
      expression was triggered by these drugs. Analysis of cell cycles showed little
      disruptions with 5-azacytidine and sodium butyrate, but an important blockage in
      the S-phase following 5-aza 2'-deoxycytidine treatment was observed. This
      approach allows a rapid identification and study of environmental demethylating
      agents.

PMID- 1382841
TI  - Expression of the class VI intermediate filament nestin in human central nervous
      system tumors.
AB  - Tumor cells of a particular tissue may show a pattern of gene expression
      characteristic of the precursor cells of this tissue. To test this proposition
      for tumors of the central nervous system (CNS) we have used immunohistochemistry
      to analyze the expression of nestin in primary human CNS tumors and corresponding
      nonneoplastic brain tissue. Nestin defines a recently discovered sixth class of
      intermediate filament proteins and in the rat is expressed predominantly in CNS
      stem cells. In the adult nonneoplastic human brain we have detected only nestin
      expression in occasional endothelial cells. In contrast, a variety of primary CNS
      tumors contained substantially elevated nestin levels. The nestin-positive cells
      in the tumor tissue were tumor cells and/or endothelial cells. Glioblastomas
      expressed higher nestin levels than less malignant gliomas. This may indicate a
      correlation between nestin expression and malignancy within the glioma tumor
      group. In the primitive neuroectodermal class of tumors we observed both nestin
      expressing and nonexpressing tumors, suggesting that nestin expression could be
      used to further characterize this complex and heterogeneous tumor group. Nine
      metastatic carcinomas were studied, and none showed nestin immunoreactivity in
      tumor cells. In conclusion, our data support the notion that primary CNS tumors
      share gene expression patterns with primitive, undifferentiated CNS cells and
      that nestin, like other intermediate filaments, may be useful in tumor diagnosis.

PMID- 1382842
TI  - Association between hepatitis C virus and hepatocellular carcinoma using assays
      based on structural and nonstructural hepatitis C virus peptides.
AB  - Stored sera from 181 Greek patients with hepatocellular carcinoma (HCC), 35
      patients with metastatic liver cancer, and 416 hospital controls with diagnoses
      other than malignant neoplasm or liver disease were examined with first and
      second generation hepatitis C virus (HCV) enzyme immunoassays as well as with
      five HCV supplemental assays based on structural and nonstructural HCV peptides.
      Second generation HCV enzyme immunoassays were more sensitive than first
      generation assays. However, both assays had suboptimal specificity using the
      standard reactivity criterion (absorbance of sample to cutoff greater than or
      equal to 1.0). Specificity was improved by centrifugation and by using a sample's
      optical density to cutoff ratio greater than or equal to 3.0 or supplemental
      assays; in this instance the prevalence of antibodies to HCV was 13.3% (24 of
      181), 0 (0 of 35), and 1.4% (6 of 416) in HCC, metastatic liver cancer, and
      hospital controls, respectively. A similar estimation of prevalence of antibody
      to HCV in HCC (12.5% or 4 of 32) was obtained when the recombinant immunoblot
      assay, second generation, was used to screen a random sample of HCC patients. The
      relative risk linking HCV to HCC was estimated as 10.4 (95% confidence interval,
      4.2-26.0; P less than 0.0001). These data suggest that the prevalence of
      antibodies to HCV in HCC using stored sera has been previously overestimated even
      though the evidence of a causal association of HCV with HCC persists.

PMID- 1382843
TI  - Reduced expression of the low affinity nerve growth factor receptor in benign and
      malignant human prostate tissue and loss of expression in four human metastatic
      prostate tumor cell lines.
AB  - In the human prostate, a low affinity (p75) nerve growth factor (NGF) receptor
      (NGF-R) localizes to the epithelia while a NGF-like protein localizes to the
      stroma. This NGF-like ligand, derived from prostate stromal cell cultures, has
      been shown to participate in paracrine mediated growth of a human tumor
      epithelial cell line (TSU-prl) in vitro. In order to investigate the role of the
      NGF-R in neoplastic growth we have examined the expression of the NGF-R in normal
      prostate tissues, benign prostatic hyperplasia tissues, adenocarcinoma tissues,
      and four metastatic tumor cell lines of the human prostate. In primary epithelial
      cell cultures of normal human prostate the p75 NGF-R was localized by
      immunocytochemistry to cytoplasmic vesicles. Furthermore, Western blot analysis
      of the NGF-R in subcellular fractions of normal prostate tissue identified an
      M(r) 75,000 immunoreactive protein in the microsomal fraction under nonreducing
      conditions of sodium dodecyl sulfatepolyacrylamide gel electrophoresis. However,
      microsomal preparations of five prostatic adenocarcinoma and five benign
      prostatic hyperplasia specimens showed varying immunoreactivity among samples,
      all of which expressed less of the p75 NGF-R than the normal tissue.
      Interestingly, microsomal preparations of the human prostatic epithelial cell
      lines, TSU-prl, DU-145, PC-3, and LNCaP did not show NGF-R expression by
      immunoblot analysis. Hence, expression of the p75 NGF-R in normal prostate
      tissue, partial loss of NGF-R expression in benign and malignant prostate tissue,
      and complete loss of NGF-R expression in the four metastatic tumor cell lines,
      suggests an inverse association of p75 NGF-R expression with the neoplastic
      progression of the human prostate.

PMID- 1382844
TI  - Expression of carcinoembryonic antigen and its predicted immunoglobulin-like
      domains in HeLa cells for epitope analysis.
AB  - Carcinoembryonic antigen (CEA) is a member of the immunoglobulin gene superfamily
      with one predicted variable domain-like region (N domain; 108 amino acids) and
      three sets of constant domain-like regions (A1B1, A2B2, and A3B3; 92 amino acids
      for A domains and 86 amino acids for B domains). In addition, CEA possesses two
      signal peptides, one at the amino terminus and one at the carboxyl terminus. Both
      are removed during posttranslational processing, with the one at the carboxyl
      terminus being replaced by a glycosylphosphatidylinositol (GPI) moiety. We have
      previously expressed the full length complementary DNA clone for CEA in Chinese
      hamster ovary cells and murine L cells, demonstrating proper processing of
      nascent polypeptide chains to mature, fully glycosylated CEA including the GPI
      anchor. Using the same full length CEA complementary DNA clone and the polymerase
      chain reaction, we have now constructed expression clones for secreted versions
      of the N domain, the A3B3 domain, and the A3 and B3 subdomains. The clones were
      expressed in HeLa cells using the beta-actin promoter. A stop codon was
      introduced at the end of the A3B3 and the A3 and B3 domains to allow secretion
      instead of retention on plasma membranes with the GPI anchor. Expressed products
      were purified to homogeneity by affinity chromatography using monoclonal
      antibodies specific for each domain and by reversed phase high pressure liquid
      chromatography. Purified domains were characterized by Western blotting, antibody
      binding and inhibition studies, amino-terminal sequence and amino acid analyses,
      and laser desorption/time of flight mass spectrometry. These analyses revealed
      that the monomeric N domain is of size 15,990, with a glycosylation mass of about
      4100, in good agreement with two N-linked glycosyl units of about mass 2100.
      There is some evidence that the N domain forms dimers. The N domain reacted with
      antibodies specific for this domain with an affinity similar to that of intact
      CEA. The A3B3 domain had a mass of 34,462, with a glycosylation mass of 14,900,
      in good agreement with seven N-linked glycosylation sites of average mass 2100.
      The A3B3 domain reacted only with antibodies specific for this domain, with a
      slightly lower affinity than that of native CEA. The amino-terminal sequences of
      the N domain and A3B3 domain proteins demonstrated proper processing of the
      signal peptide.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1382845
TI  - Antigen-specific activity of carcinoma-reactive BR64-doxorubicin conjugates
      evaluated in vitro and in human tumor xenograft models.
AB  - The anticarcinoma antibody BR64 was conjugated to a doxorubicin derivative,
      doxorubicin 13-[3-(2-pyridyldithio)propionyl]hydrazone, and the resulting
      conjugates (BR64-DOX) were evaluated for activity and immunological specificity
      in vitro and in human tumor xenograft models. The BR64-DOX immunoconjugates
      retained immunoreactivity and cytotoxicity and demonstrated antigen-specific
      cytotoxicity in vitro. The potency of BR64-DOX immunoconjugates in vitro was
      related to the drug:monoclonal antibody mole ratio of the conjugates. The
      antitumor activity of BR64-DOX conjugates was consistently superior to the
      maximal activity obtained with the parent drug, doxorubicin (DOX), in established
      human lung and human breast carcinoma xenograft models. The superior antitumor
      activity of BR64-DOX conjugates was reflected both in tumor growth inhibition and
      in regressions and cures of established tumors following the administration of
      tolerated doses of BR64-DOX. The antitumor activity of BR64-DOX conjugates was
      not the result of synergism between monoclonal antibody BR64 and DOX, because
      mixtures consisting of monoclonal antibody and optimized DOX were not more active
      than an equivalent dose of DOX administered alone. The antitumor activity of BR64
      DOX conjugates was antigen specific; equivalent doses of nonbinding isotype
      matched conjugates were not active against established tumor xenografts.

PMID- 1382846
TI  - Down-regulation of keratin 14 gene expression after v-Ha-ras transfection of
      human papillomavirus-immortalized human cervical epithelial cells.
AB  - Keratin expression in human cervical squamous cell carcinoma (SCC) lines differed
      significantly from both normal and human papillomavirus (HPV) immortalized
      exocervical cells. Keratin 14 (K14) expression, determined by protein synthesis
      and mRNA levels, was dramatically down-regulated in the cervical SCC lines while
      keratin 5 (K5) expression was not. K14 expression was similarly down-regulated in
      an HPV-16 immortalized cervical cell line after tumorigenic transformation with
      recombinant v-Ha-ras DNA. Cultures derived from nude mouse tumor explants also
      exhibited an altered keratin profile and the levels of K14 protein synthesis, as
      well as K14 mRNA, were not detectable. In both cases K5 protein synthesis was not
      significantly down-regulated. In addition, neoplastic cervical SCC lines
      exhibited up-regulation of keratins 7, 8, 13, and 19, combined with slight down
      regulation of keratins 6 and 16. Epidermal keratinocytes responded in a different
      manner to exocervical cells. Transfection of human papillomavirus-immortalized
      epidermal keratinocytes with the BglII N fragment of herpes simplex virus 2
      produced a neoplastic cell line, but K5 and K14 expression remained unchanged.
      Thus, neoplastic transformation of human exocervical cells, both in vivo
      (spontaneous cervical SCC) and in vitro (HPV-16- and v-Ha-ras-induced cervical
      SCC), is accompanied by characteristic changes in keratin expression. The
      specific down-regulation of K14 in these tumorigenic cervical cells, in the
      absence of significant changes in the expression of K5, implies that the normal
      coordinate regulation of K5 and K14 gene expression has been uncoupled.

PMID- 1382847
TI  - The T-cell receptor V beta gene usage in tumor-infiltrating lymphocytes and blood
      of patients with hepatocellular carcinoma.
AB  - To determine a possibly restricted T-cell receptor (TCR) repertoire in tumor
      infiltrating lymphocytes (TIL) in response to tumor-associated antigens in
      patients with hepatocellular carcinoma (HCC), freshly isolated TIL (n = 5) and
      peripheral blood lymphocytes (PBL; n = 6; 3 paired with TIL) were studied for
      expression of TCR variable (V) beta regions. RNA purified from TIL or PBL was
      reverse-transcribed into complementary DNA. This complementary DNA was amplified
      by quantitative polymerase chain reaction with 22 primers specific for 20 TCR V
      beta gene families and a 3' constant (C) beta primer. As a reference for later
      quantitation, a fragment of TCR C alpha was coamplified with each V beta region.
      Using 32P-labeled 3' primers, the percentage of total V beta expression was
      calculated by measuring the cpm of each of the amplified products. In contrast to
      PBL of 6 control, healthy individuals, whose range of expression of each TCR V
      beta gene varied from 0 to 13%, the expression of some V beta genes in HCC TIL
      was as high as 33%, indicating a restricted TCR V beta usage in HCC TIL. When
      polymerase chain reaction-amplified complementary DNAs of the V beta 1 or V beta
      3 genes obtained from two TIL preparations were cloned and sequenced, the same
      rearrangements were found in the majority of DNA clones. The particular V beta
      genes that were over- or underrepresented in TIL varied among the patients. In 3
      of 6 PBL and 3 of 5 TIL, the V beta 3 gene was expressed with a relatively high
      frequency. The V beta 4 gene expression was consistently low in patients' TIL or
      PBL. In 3 paired PBL and TIL, V beta expression was similar. In 5 of 6 cases, HCC
      PBL had different TCR V beta frequencies from those seen in normal PBL. This
      analysis of TCR V beta usage in freshly isolated TIL and in PBL indicated that T
      lymphocytes in patients with HCC might have restricted immunological reactivity
      and that V beta 3-restricted TIL might represent antitumor effector cells.

PMID- 1382848
TI  - Identification of immunogenic human melanoma antigens in a polyvalent melanoma
      vaccine.
AB  - An essential element in the development of effective vaccines against human
      malignant melanoma is the identification of antigens which are relevant for
      vaccine construction as evidenced by their ability to stimulate antimelanoma
      immune responses in humans. In this study, we identified immunogenic melanoma
      antigens using as probes antibodies induced in patients immunized with a vaccine
      which contains a broad range of potential immunogens. By
      immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      analysis of detergent lysates of radioiodinated melanoma cells, we found that 17
      (65%) of 26 patients sequentially immunized with a polyvalent melanoma antigen
      vaccine developed antibodies to one or more melanoma cell surface antigens with
      approximate molecular weights of 38,000-43,000, 75,000, 110,000, 150,000, and
      210,000. The immunodominant antigens which most frequently stimulated antibody
      responses were the M(r) 110,000 antigen followed by the M(r) 210,000 and 38,000
      43,000 antigens, which induced antibody responses in 62%, 27%, and 19% of
      patients, respectively. These three antigens were commonly expressed on different
      melanomas but rarely on nonmelanoma cells and are unrelated to class I or II
      human leukocyte antigens or to the previously described p97 or M(r) 240,000
      proteoglycan melanoma-associated antigens. Thus, these three antigens are
      attractive candidates for the construction of melanoma vaccines, because they are
      immunogenic in humans and are preferentially expressed on melanomas.

PMID- 1382849
TI  - Expression of tumor-associated epitopes on Epstein-Barr virus-immortalized B
      cells and Burkitt's lymphomas transfected with epithelial mucin complementary
      DNA.
AB  - Mucins are among the best described human tumor-associated antigens. At least 73
      tumor-reactive anti-mucin antibodies have been described; in addition, we have
      previously demonstrated the existence of tumor-specific cytotoxic T-lymphocyte
      epitopes on the mucin produced by breast and pancreatic tumors. To determine
      whether the appearance of tumor-associated mucin epitopes can be explained by
      altered post-translational modification of mucin in tumors, or whether the
      generation of these epitopes requires changes in the mucin gene itself, we
      studied four Burkitt's lymphomas and six Epstein-Barr virus-immortalized B-cell
      lines transfected with an expression construct containing the mucin complementary
      DNA. Transfected cell lines showed stable maintenance of the mucin gene, which
      comprises 20 or more tandem repeats of a 60-nucleotide sequence. Transfected
      cells expressed many tumor-associated mucin epitopes, suggesting that the changes
      in mucin synthesis seen in breast and pancreatic tumors are present in other
      malignant cell types as well. Furthermore, even though each cell line was
      transfected with the identical mucin construct, each expressed a different subset
      of tumor-associated mucin epitopes. This suggests that the specificity of these
      epitopes for tumors is not due to genetic alterations of the mucin gene in
      tumors. Incubating transfected cells with phenyl-N-acetyl-alpha-galactosaminide,
      an inhibitor of O-linked glycosylation, altered cell surface carbohydrate
      structures and resulted in increased expression of all tumor-associated epitopes,
      implicating incomplete glycosylation of mucin in the generation of these
      epitopes. These findings suggest that alterations in the posttranslational
      modification of normal gene products can result in the expression of novel
      epitopes. Furthermore, the ability to transfect cancer patients' Epstein-Barr
      virus-immortalized B-cell lines with mucin will provide an unlimited supply of
      autologous, mucin-bearing cells with which to study these patients' T-cell
      response to mucin.

PMID- 1382850
TI  - Presence of ras oncogene mutations and human papillomavirus DNA in human prostate
      carcinomas.
AB  - The frequency of H-ras, K-ras, and N-ras mutations and the presence of high-risk
      human papillomavirus (HPV 16, 18, and 33) DNA were studied in 75 paraffin
      embedded specimens obtained from 68 Japanese patients with a variety of prostate
      carcinomas by using polymerase chain reaction and DNA hybridization with sequence
      specific oligonucleotides. Ten specimens each of normal and benign hyperplastic
      prostatic tissues from the same number of patients were also examined for this
      analysis. Of 68 carcinoma cases, ras gene mutations were present in 16 cases
      (24%) and HPV DNAs in 28 cases (41%). Eleven mutations were detected in codon 61
      of H-ras, 4 in codon 12 of N-ras, and 2 in codon 61 of K-ras. HPV 16, 18, and 33
      DNAs were found in 11, 17, and 5 cases, respectively. Eight of the 16 cases with
      ras mutation also harbored HPV DNAs. The frequency of ras mutations and the HPV
      infection increased in patients with advanced stages of the tumor and with the
      higher Gleason score. There was the predominant presence of H-ras codon 61.2 (CAG
      ->CTG) mutation and HPV 18 DNA in prostatic carcinomas metastasizing to the bone.
      None of the normal or benign hyperplastic prostatic specimens contained either
      ras mutation or HPV DNA. Our results suggest that ras gene mutations and HPV
      infections are relatively frequent, at least in prostate carcinoma of Japanese
      patients. These two factors appear to be related to the progression of the tumor.
      Moreover, H-ras codon 61.2 mutation and HPV 18 infection may have some predictive
      roles for bone metastasis in prostate carcinoma.

PMID- 1382851
TI  - Detection of hematogenous micrometastasis in patients with prostate cancer.
AB  - The goal of this study was to determine if patients with stage D0-3 prostatic
      adenocarcinoma have detectable hematogenous micrometastasis. Polymerase chain
      reaction amplification of prostate-specific antigen mRNA, which is exclusively
      expressed by prostatic epithelial cells, was used to detect circulating prostatic
      cells. Peripheral venous blood was obtained from 17 control and 12 prostate
      cancer patients with stage D0-3 prostatic adenocarcinoma. Of the 12 cancer cases,
      four patients (stage D1-3) tested positive for prostate-specific antigen RNA,
      indicating the presence of circulating micrometastasis. The 17 negative controls
      all tested negative. Contrary to a long held hypothesis, these data point to the
      possibility that hematogenous metastasis may be a relatively early event in the
      natural history of human prostate cancer. These findings may have an important
      impact on our understanding and treatment of prostate cancer.

PMID- 1382852
TI  - Age-related immunoreactivity pattern in medulloblastoma.
AB  - Thirty-five paraffin-embedded medulloblastomas (19 from children and 16 from
      adults; 24 classic medulloblastomas, 10 desmoplastic medulloblastomas, 1 tumor
      with neuronal differentiation) were examined for reactions with antibodies
      against glial fibrillary acidic protein (GFAP), cytokeratins KL1 and MNF116,
      desmin, and vimentin. Only the tumor from the youngest patient, a 152-day-old
      boy, showed a positive immunoreaction for cytokeratins. Because of this age
      related expression of cytokeratins in medulloblastomas primarily in very young
      children, cytokeratin positivity was interpreted as a sign of tumor immaturity.
      Five medulloblastomas showed scattered GFAP-positive reactive astrocytes and/or
      other positive, probably neoplastic, cells. Only two tumors showed GFAP
      immunoreactivity in unequivocally neoplastic cells. Of six tumors that reacted
      with vimentin, three showed strong reactivity throughout, one being the tumor
      from the 152-day-old boy. The remaining three demonstrated nests of vimentin
      positive cells with weak or intense somatic immunoreactivity for vimentin. None
      of the 35 cases showed positivity for desmin; indicating that mesenchymal
      differentiation is restricted to the rare so-called medullomyoblastomas.

PMID- 1382853
TI  - A nuclear magnetic resonance spectroscopic investigation of Kdo-containing
      oligosaccharides related to the genus-specific epitope of Chlamydia
      lipopolysaccharides.
AB  - The 1H- and 13C-NMR parameters, chemical shifts and coupling constants, for the
      pentasaccharide of the genus-specific epitope of Chlamydia lipopolysaccharide and
      related di-, tri-, and tetra-saccharides have been measured and assigned
      completely using 1D and 2D techniques, and their structures have been confirmed.
      NOE experiments indicated the preferred conformation of the pentasaccharide and
      the component oligosaccharides. The 3JH,H demonstrate a change in conformation by
      rotation of the C-6-C-7 bond of the side chain of the (2----8)-linked Kdo (unit
      b) in alpha-Kdo-(2----8)-alpha-Kdo-(2----4)-alpha-Kdo-(2----6)-beta-GlcN-(1--- 
      6)- GlcNol, alpha-Kdo-(2----8)-alpha-Kdo-(2----4)-alpha-Kdo-(2----6)-beta-GlcNAc
      (1- ---O)- allyl, and alpha-Kdo-(2----8)-alpha-Kdo-(2----4)-alpha-Kdo-(2----O)
      allyl relative to that preferred in alpha-Kdo-(2----4)-alpha-Kdo-(2----6)-beta
      GlcNAc-(1----O)-allyl, alpha-Kdo-(2----8)-alpha-Kdo-(2----O)-allyl, alpha-Kdo-(2-
      --4)-alpha-Kdo-(2----O)-allyl, and alpha-Kdo-(2----6)-beta-GlcNAc-(1----O)-allyl,
      irrespective of the size of the aglycon, e.g., allyl or beta-D-GlcN residues. The
      conformational results have been substantiated by computer calculations using the
      HSEA approach.

PMID- 1382854
TI  - Binding studies on internal immunodeterminants: synthesis of beta-(1----6)-linked
      oligosaccharide methyl glycosides having one to four internal D-galactopyranosyl
      residues flanked by gentiobiose residues.
AB  - The oligosaccharide glycosides beta-D-Glcp-(1----6)-beta-D-Glcp-(1----6)-[beta-D
      Galp-(1----6)]n-beta-D - Glcp-(1----6)-beta-D-Glcp-1----OMe (n = 1-4) were
      prepared by a convergent block synthesis. Haloacetyl, tert-butyldiphenylsilyl,
      and dimethylthexylsilyl groups were used as temporary protective groups for the
      preparation of the intermediate glycosyl donors and acceptors. The deoxygenated
      trisaccharide glycosides beta-D-Glcp-(1----6)-beta-D-Galp-(1----6)-4-deoxy-beta-D
      xylo-Hexp -1----OMe and beta-D-Glcp-(1----6)-4-deoxy-beta-D-xylo-Hexp-(1----6)
      beta-D-Galp -1----OMe were also synthesized. The binding of each glycoside to the
      monoclonal antigalactan antibody IgA J539 was studied and the results support the
      previous finding that J539 can bind to internal antigenic epitopes. The data are
      consistent with the interpretation that subsite C of that antibody binds glucose
      with a Ka of approximately 6 (cf. 10.9 for galactose).

PMID- 1382855
TI  - Combined chemical-enzymic synthesis of an internally monofucosylated
      hexasaccharide corresponding to the CD-65/VIM-2 epitope: use of a terminal alpha
      2-6-linked N-acetylneuraminic acid as a temporary blocking group.

PMID- 1382856
TI  - Monoclonal antibodies anti-CD3, anti-TCR alpha beta and anti-CD2 act
      synergistically with tumor cells to stimulate lymphokine-activated killer cells
      and tumor-infiltrating lymphocytes to secrete interferon gamma.
AB  - Peripheral blood lymphocytes cultured in interleukin-2 IL-2 acquire the ability
      to recognize and kill a wide range of tumor cells. Such promiscuous killer cells
      are termed lymphokine-activated killer (LAK) cells. We recently reported that the
      interaction of LAK cells with tumor cells stimulated the LAK cells to release
      interferon (IFN) gamma. Here, we report that the release of IFN gamma by LAK
      cells can be further enhanced by addition of the monoclonal antibodies (mAbs),
      anti-CD3, anti-(T cell receptor alpha beta) (TCR alpha beta) and a mitogenic
      combination of anti-CD2 (T112 + T113). Other antibodies, including a non
      mitogenic anti-CD2 mAb (Leu5b), that recognize T cell-associated antigens were
      not stimulatory. The same stimulatory mAbs also synergized with tumor cells to
      stimulate tumor-infiltrating lymphocytes (TIL) to secrete IFN gamma. Additional
      experiments indicated that it was the T cell subset of LAK cells (LAK-T cells)
      that was stimulated by tumor cells and mAbs to release IFN gamma. Inhibition
      studies with specific mAbs suggest that the stimulation of IFN gamma release by
      LAK-T cells was dependent both on the aggregation of TCR-CD3 complexes on the LAK
      T cell, and on the interaction of accessory molecules with their ligands. The
      accessory molecules we have identified as critical are LFA 1 and CD2/LFA-2 on LAK
      T cells interacting with their respective ligands ICAM-1 and LFA3. Thus our data
      suggest that cytokine production in LAK-T cells can be regulated by multiple
      molecular interactions, involving the TCR-CD3 complex and adhesion molecules.

PMID- 1382857
TI  - Effects of lipopolysaccharide on interleukin-2-induced cytotoxic activity of
      murine splenocyte cultures: role of prostaglandin E2 and interferons.
AB  - Splenocytes cultured for 24 h in the presence of interleukin-2 (IL-2),
      lipopolysaccharide (LPS) or both together expressed a cytotoxic activity against
      the YAC-1 lymphoma cell line and to a lesser extent against P815 mastocytoma
      cells. The association of IL-2 and LPS had an additive effect on induction of
      cytotoxicity. The IL-2-induced cytotoxic activity lasted for the whole of the
      culture; however, the addition of LPS at the initiation of the culture increased
      the cytotoxic activity during its the early phase, the increment being followed
      by a fall of lytic activity after 72 h of culture. Assessment of interferon (IFN)
      in the culture supernatants showed (a) a production of IFN gamma by IL-2
      supplemented cultures, (b) a more potent IFN production by cultures treated with
      IL-2 plus LPS (including 20% IFN alpha/beta, (c) and that indomethacin (1 microM)
      potentiated the effect of either IL-2 or LPS used alone but did not significantly
      increase the cytotoxic activity of cultures treated with IL-2 plus LPS (the one
      that produced a high level of IFN). When cultures were treated by an anti-IFN
      gamma antibody we observed no change in the cytotoxic activity; however, in the
      presence of anti-IFN alpha/beta serum the cytotoxic activity of cultures treated
      with IL-2 plus LPS was inhibited after 24 h but stimulated after 72 h. When
      cultures treated with IL-2 plus LPS were supplemented with both indomethacin and
      anti-IFN alpha/beta the cytotoxic activity assessed after 72 h of culture was
      maintained at the same level as that of IL-2-treated cultures, hence the fall
      after 72 h of the cytotoxicity of cultures initiated in the presence of LPS alone
      was affected by both the immune serum and the cyclooxygenase inhibitor.
      Altogether these data show that when splenocytes are cultured for more than 72 h
      in the presence of IL-2 and LPS their cytotoxic activity decreases, and it is
      likely that this diminution is linked to the endogenous production of
      prostaglandin E2 and INF alpha/beta.

PMID- 1382859
TI  - Influence of crisis on haemoglobin F level in adult Nigerian sickle cell anaemia
      patients.
AB  - Forty-six Nigerian adult sickle cell anaemia patients were investigated, each in
      sickle cell crisis and steady state. Forty-three patients had vaso-occlusive
      crisis while three had haemolytic episodes. Investigations included Packed Cell
      Volume (PVC), Reticulocyte count and Haemoglobin F estimation. PCV was carried
      out by the microhaematocrit method while the reticulocytes were counted manually.
      Haemoglobin F was estimated by the Alkali Denaturation Technique. There was
      significant anaemia (p < 0.05) and reticulocytosis (p < 0.0001) during the period
      of crisis compared to the steady state. There was no significant difference (p >
      0.05) between HbF level in crisis and that in the steady state. In other words
      the previously documented increase in HbF during reticulocyte response did not
      take place in our model. Maybe a 'critical' level of reticulocytosis was not
      attained. It was also shown that vaso-occlusive crisis did not induce an increase
      in HbF level suggesting that HbF might be genetically determined at a constant
      low level throughout life in each of our patients.

PMID- 1382858
TI  - Voltage-clamp study of calcium currents during differentiation in the NCB-20
      neuronal cell line.
AB  - 1. Calcium currents (ICa) were studied in voltage-clamped NCB-20 cells. In
      undifferentiated cells, voltage steps from hyperpolarized potentials (-80/-100
      mV) essentially revealed transient ICa showing characteristics classically
      described for "T-type" channels. In about 50% of the cells, there was a residual
      current at the end of the step; no ICa was elicited from a holding potential of 
      50 mV. 2. In contrast, 100% of the cells differentiated with dibutyryl cyclic AMP
      (cAMP) displayed a residual current in addition to the transient one, and
      depolarizing steps from a holding potential of -50 mV induced a sustained
      current. In these cells, Bay K 8644 elicited both a negative shift in voltage
      dependence and a moderate increase of the sustained component. 3. Although these
      changes in Ca2+ channel physiology result from chemically induced
      differentiation, they might not be directly related to the concomitant
      morphologic differentiation. 4. In undifferentiated NCB-20 cells, T-type Ca2+
      currents can be elicited in relative isolation.

PMID- 1382860
TI  - Separation of drug transport and chloride channel functions of the human
      multidrug resistance P-glycoprotein.
AB  - The human multidrug resistance P-glycoprotein is an active transporter that pumps
      cytotoxic drugs out of cells. Expression of P-glycoprotein is also associated
      with a volume-activated chloride channel. Here we address the relationship
      between these two functions. Drug transport requires ATP hydrolysis while, in
      contrast, ATP binding is sufficient to enable activation of the chloride channel.
      The chloride channel and drug transport activities of P-glycoprotein appear to
      reflect two distinct functional states of the protein that can be interconverted
      by changes in tonicity. Transportable drugs prevent channel activation but have
      no effect on channel activity once it has been preactivated by hypotonicity. The
      transport and channel functions of P-glycoprotein have been separated by directed
      mutations in the nucleotide-binding domains of the protein. These data provide
      further evidence that P-glycoprotein is bifunctional with both transport and
      channel activities. Implications for the design of chemotherapeutic drugs and for
      the function of the related cystic fibrosis gene product, CFTR, are discussed.

PMID- 1382861
TI  - IL-6 enhances the cytotoxic activity of thymocyte-derived CD56+ cells.
AB  - Thymocyte-derived lymphokine-activated killer (LAK) cells were used as a model
      for the study of the cytokine driven development of cytotoxicity. These cells are
      devoid of initial cytotoxic activity but upon culture in IL-2 they develop into
      cytotoxic effectors. The parameters of the response of thymocytes to IL-6 are
      similar to that of PBL in that IL-6, at concentrations as low as 1 mu/ml,
      increases cytotoxicity of thymocyte-LAK cells when generated in low doses (25-50
      mu/ml) of IL-2. IL-6-enhanced thymocyte-LAK cytotoxicity is observed when tested
      against both NK-resistant and NK-sensitive tumor cell lines. IL-6 alone does not
      induce any cytotoxicity from thymocytes nor does IL-6 change the time course of
      thymocyte-LAK cell generation in IL-2 culture. IL-6 does not affect DNA
      synthesis, total cell number, proportion of CD56+ cells, or the expression of IL
      2R (both P55 and P75 glycoproteins) in IL-2-cultured thymocytes. Instead, IL-6
      used to treat mature thymocyte-LAK effector cells for as little as 1 hr prior to
      51Cr-release assay increases LAK cytotoxicity. This enhancement is abrogated by
      pretreatment of effector cells with cycloheximide, suggesting that protein
      synthesis is required for IL-6 to enhance LAK cell activity. The precursor
      phenotypes of IL-6-responsive thymocyte-LAK cells are CD3-/CD5-. The effector
      phenotypes of IL-6-enhanced thymocyte-LAK cells are CD5-/CD56+. Thus, IL-6
      depends on synthesis of rapid-turnover proteins to act on mature CD56+/CD5- LAK
      cells to increase their cytotoxic function.

PMID- 1382862
TI  - Negative modulation of human NK cell activity by purinoceptors. 2. Age
      associated, gender-specific partial loss of sensitivity to ATP.
AB  - Aging is known to modulate the affinity and sensitivity of receptors for hormones
      and regulatory molecules. We have shown previously that exogenous adenosine
      triphosphate (ATP), perhaps acting as a purinoceptor agonist, can down-regulate
      the cell-mediated anti-tumor natural cytotoxic activity of human peripheral blood
      natural killer (NK) cells. We have extended these studies to investigate whether
      this effect is modulated during immunosenescence, and if so, whether it is gender
      restricted or NK subset-associated. While the inhibitory effect is demonstrable
      in most individuals, there is a gender-restricted, age-associated transition in
      the sensitivity of NK cell activity to inhibition by ATP at 2.5 x 10(-5) to 80 x
      10(-5) M in vitro. Data from both suboptimal (100 microM) and optimal (800
      microM) inhibitory doses of ATP support this conclusion. The ID20ATP were 10.2 x
      10(-5) and 17.8 x 10(-5) M for the young (less than 40 years) and elderly
      (greater than 70 years) females, respectively (P = 0.02). The frequency
      distribution curve of ATP sensitivity shifts to the left in the elderly, i.e.,
      the sensitivity to be inhibited at 50% or more by ATP was expressed by one-half
      of young and one-fifth of elderly female donors. Linear regression analysis
      suggests an inverse relationship between percentage CD57+ and percentage CD16+57+
      (but not percentage CD16+) NK subsets and sensitivity to down-regulation by ATP.
      The mean percentage of the above NK cell phenotypes among lymphocytes from young
      and old female donors differ significantly (less than 0.0001). The data suggest
      that the presence of CD57 antigen-positive cells may render NK cells relatively
      more resistant to the action of purinoceptor agonists such as ATP. Thus in
      females, immunosenescence results in a diminished ability of NK cells to
      transduce those signals that may normally mediate ATP-induced suppression of NK
      cytolytic activity. Such a diminished ability may be an immunobiological
      advantage to aging NK cells since they can be kept at a higher steady-state level
      of (anti-tumor cytotoxic) activity through a protection from negative modulators.
      These findings have an implication on the lower rate of mortality due to cancer
      seen in older women compared to that in older men. It is suggested that the ATP
      NK cell interaction through the P2 purinoceptor may serve as a potentially useful
      model to study immunosenescence, ontogenic, or gender-specific changes in NK
      cells at the cell surface level.

PMID- 1382863
TI  - The inhibition of T cell proliferative responses by crosslinking CD7 and IgM-Fc
      receptors.
AB  - Previous work from our laboratory described a human T cell soluble ligand that
      inhibited T cell proliferative responses to mitogen and alloantigen by
      interacting with CD7 and/or the receptor for the IgM-Fc portion (FcR mu) on T
      cells. In this report, we used mouse anti-human CD7 monoclonal antibodies (mAb)
      and purified human IgM (HIgM) to substitute for the human ligand and examined the
      possible involvement of these receptors in the inhibition of T cell
      proliferation. Preincubation of human T cells with mouse anti-CD7 mAb, HIgM,
      mouse anti-human IgM (MAH IgM) alone, or any of these combinations as a primary
      antibody did not inhibit mitogen- or alloantigen-induced T cell replication.
      Similar effects were seen with the pretreatment of T cells with an irrelevant
      negative control primary mAb or a secondary-step goat anti-mouse immunoglobulin
      (GAM Ig), goat anti-human IgM-Fc (GAH Fc mu), or both. In contrast, the
      pretreatment of T cells with anti-CD7 and/or HIgM followed by the appropriate
      secondary-step crosslinking antibody significantly reduced their proliferative
      responses to mitogen and alloantigen. Similarly, crosslinking of CD7 and FcR mu
      on human transformed T cell lines inhibited their spontaneous proliferation. The
      inhibitory effect of crosslinking CD7 and FcR mu was not due to cytotoxic effects
      of these antibodies and appears to be temperature sensitive. These findings
      suggest that crosslinking CD7 and/or FcR mu appears to have a novel role in down
      regulating T cell proliferation.

PMID- 1382864
TI  - B cells from subjects with CVI can be driven to Ig production in response to CD40
      stimulation.
AB  - The majority of patients with common variable immunodeficiency (CVI) have low to
      normal numbers of membrane Ig-bearing B cells; yet these cells fail to
      differentiate in vivo resulting in hypogammaglobulinemia. We have suggested that
      the differentiation failure of CVI B cells is related to a failure to respond
      appropriately to signals involved in terminal B cell differentiation as most CVI
      subjects' cells undergo activation and proliferation normally. Whether this
      failure relates to a direct "intrinsic" defect in the B cells or is secondary to
      a lack of appropriate T cell or other influences in vivo is uncertain. We have
      previously reported that the majority of patients with CVI have elevated
      circulating levels of IL-6. We now show that the IL-6 produced by these patients
      is functionally normal. Additionally, the display of IL-6 receptors on in vitro
      stimulated CVI B cells is normal. However, we found that the patients' cells do
      not make IgE in response to an IL-6/T-cell-dependent differentiation pathway
      employing exogenous interleukin-4 (IL-4). The failure to respond in the IL-6
      dependent system could not be overcome by exogenous IL-6 or varying doses of IL
      4. In contrast, when stimulated by CD40 plus IL-4 in a differentiation pathway
      that does not require IL-6, B cells from CVI patients were stimulated to produce
      IgE. These findings, along with our earlier data showing that 13-cis-retinoic
      acid can drive maturation in CVI patients, strengthen the concept that B cells in
      patients with CVI have the potential for terminal differentiation but do not
      appear to achieve this in vitro or in vivo through a polyclonal Ig
      differentiation pathway that employs IL-6 as one of its maturation signals.

PMID- 1382865
TI  - Cytokine-induced differentiation of cultured nonadherent macrophages.
AB  - Monocytes were isolated from peripheral blood and cultured in vitro for more than
      3 weeks in glass chamber slides. Phenotypically and ultrastructurally these
      nonadherent macrophages (NAM) appear similar to connective tissue resident
      macrophages. They constitutively secrete a high amount of IL-1ra and little or no
      IL-1 alpha or IL-1 beta. When exposed to GM-CSF, IL-2, or IFN-gamma for 24 hr,
      NAM become adherent and undergo dramatic morphological changes. Cytokines
      treatment primes NAM for increased LPS-mediated TNF production and these GM-CSF-
      and LPS-treated NAM are cytotoxic to WEHI 164, a TNF-sensitive target.
      Morphological changes and TNF production are both inhibited by antimetabolites
      and a variety of antineoplastic drugs. Although morphology inhibition is
      reversible under certain circumstances, inhibition of TNF synthesis is
      irreversible. These findings suggest that cytokines might play a role in
      differentiation and maturation of long-term cultured monocytes. Furthermore, the
      effects of antimetabolites and antineoplastic drugs on arresting the
      differentiation processes may significantly impair antitumor functions of
      macrophages.

PMID- 1382866
TI  - Self-reactive repertoire of tight skin (TSK/+) mouse: immunochemical and
      molecular characterization of anti-cellular autoantibodies.
AB  - The tight skin (TSK/+) mouse has been proposed as an experimental model for
      progressive systemic sclerosis because of the biochemical alterations in collagen
      synthesis and pathological similarities to the human disease. Here, we report the
      analysis of tight skin mice sera for the presence of anti-cytoplasmic and anti
      nuclear autoantibodies and determination of the frequency of hybridomas producing
      anti-cellular autoantibodies. The binding specificity of TSK mAbs to nuclear and
      cytoplasmic antigens such as keratin, actin, vimentin, and mitochondria was
      determined. Of 71 monoclonal antibodies that we have studied, only 3 appear to
      bind to foreign as well as self-antigens, indicating that the majority of these
      antibodies do not belong to the class of natural autoantibodies. Our results also
      showed that the frequency of hybridomas producing anti-nuclear and anti
      cytoplasmic antibodies was higher in TSK mice than in C57BL/6 pa/pa, the control
      mouse strain, used in these studies. The results of the analysis of V gene usage
      showed that the majority of anti-cytoplasmic and anti-nuclear antibodies are
      encoded by genes from a restricted number of VH and VK genes families. In the
      sera of TSK mice we have detected the presence autoantibodies specific for
      cytoplasmic antigens in addition to anti-nuclear and anti-topoisomerase I
      antibodies which are characteristic of scleroderma. Since the presence of anti
      cytoplasmic antibodies has not been described in scleroderma, the significance of
      their production in tight skin mice is not clear. However, the presence of such
      autoantibodies in the animal model provides a basis for investigation of this
      type of antibodies in human disease.

PMID- 1382867
TI  - Resolution of adhesion- and activation-associated components of monoclonal
      antibody-dependent human NK cell-mediated cytotoxicity.
AB  - Flow cytometry was used to investigate two functional parameters of human natural
      killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC): (i)
      the frequency of NK cells which formed conjugates (NKC) with autologous
      monoclonal antibody (mAb)-coated lymphocyte target cells, a measure of the
      avidity of CD16-dependent cell-cell adhesion, and (ii) the rise in the
      intracellular concentration of ionized calcium ([Ca2+]i) elicited in NKC by
      contact with target cells, a measure of CD16-dependent NK cell activation. For
      each of four rat IgG2b mAb directed against target cell antigens CDw52, CD5,
      CD45, and class I HLA, there existed quantitatively similar relationships between
      ADCC and rise in NKC[Ca2+]i but significant inter-mAb differences with respect to
      the ADCC vs the NKC frequency relationship. Cytolytic efficiencies of mAb
      appeared to be determined at the level of the NK cell, dependent upon CD16 and
      LFA-1, but restricted with respect to quantitative levels of NKC[Ca2+]i. In
      concert with this notion, targets coated with an IgG1 isotype-switch variant
      alpha CDw52 mAb promoted significant conjugate formation but failed to elicit a
      rise in NKC[Ca2+]i or ADCC. Thus, Fc regions of antibodies make contacts with NK
      cell CD16 which may strengthen cell-cell adhesion without eliciting an activation
      stimulus, a finding which supports a complexity of CD16 functional regulation of
      probable significance in the clinical consequences of antibody responses or
      therapeutic mAb manipulations.

PMID- 1382868
TI  - Behavior of the idiotypic network in conventional immune responses. I. Kinetics
      of idiotypic and anti-idiotypic antibodies following immunization with T
      independent and T-dependent antigens.
AB  - A minimal requirement in investigations of the behavior of the idiotypic network
      during immunization is the ability to quantitate both the idiotypic (Ab1) and
      anti-idiotypic (Ab2) responses. Quantitation of Ab2 in serum is complicated by
      the simultaneous presence of Ab1, so that Ab1-Ab2 immune complexes escape
      detection. In contrast, immune complexes should not complicate the enumeration of
      Ab2-producing lymphocytes in a hemolytic plaque assay. This study utilizes a
      procedure that allows detection of Ab2-producing cells in such an assay. The
      procedure relies upon the insertion of the appropriate antibody (Ab1) into the
      membrane of indicator SRBC through a covalently attached dipalmitoyl
      phosphatidylethanolamine (DPPE) tail. When the Ab2 response following murine
      immunization with DNP-Ficoll was analyzed using such an assay, peak plaque
      forming cell (PFC) numbers were found to coincide with peak Ab1 PFC numbers in
      both the primary and secondary response. In addition, this Ab2 response was found
      to be T independent. The murine immune response to DNP-HGG demonstrated a peak
      Ab2 PFC response which followed the peak Ab1 PFC response after both primary and
      secondary immunization. This Ab2 response appeared to be T dependent. The
      secondary responses to both DNP-Ficoll and DNP-HGG showed increased levels of Ab2
      PFC and decreased levels of Ab1 PFC in comparison to the primary responses to the
      same antigens, suggesting that immunoregulation may occur within these idiotypic
      networks.

PMID- 1382869
TI  - Behavior of the idiotypic network in conventional immune responses. II. Affinity
      and heterogeneity of idiotypic and anti-idiotypic antibodies following
      immunization with T-independent and T-dependent antigens.
AB  - The relative affinity and heterogeneity of affinity of idiotypic and anti
      idiotypic antibodies in mice immunized with the T-independent antigen DNP-Ficoll
      and the T-dependent antigen DNP-HGG were measured by a plaque inhibition assay.
      Idiotypic plaque-forming cells (PFC) were detected by a conventional assay
      utilizing DNP-coated SRBC. Anti-idiotypic PFC were detected with SRBC coated with
      affinity-purified anti-DNP antibody of rabbit origin. It was found that both
      idiotypic and anti-idiotypic antibodies elicited by immunization with the T
      independent antigen had lower affinity and were less heterogeneous than the
      corresponding antibodies originating in mice immunized with the T-dependent
      antigen. In addition, the affinity and heterogeneity values of the idiotypic
      antibodies were correlated with the affinity and heterogeneity values of the anti
      idiotypic antibodies from the same mice. This finding indicates that idiotypic
      and anti-idiotypic antibodies mutually regulate each other, thus pointing to
      internal immunoregulatory effects of the idiotypic network with respect to these
      parameters.

PMID- 1382871
TI  - Association of kinesin with characterized membrane-bounded organelles.
AB  - The family of molecular motors known as kinesin has been implicated in the
      translocation of membrane-bounded organelles along microtubules, but relatively
      little is known about the interaction of kinesin with organelles. In order to
      understand these interactions, we have examined the association of kinesin with a
      variety of organelles. Kinesin was detected in purified organelle fractions,
      including synaptic vesicles, mitochondria, and coated vesicles, using
      quantitative immunoblots and immunoelectron microscopy. In contrast, isolated
      Golgi membranes and nuclear fractions did not contain detectable levels of
      kinesin. These results demonstrate that the organelle binding capacity of kinesin
      is selective and specific. The ability to purify membrane-bounded organelles with
      associated kinesin indicates that at least a portion of the cellular kinesin has
      a relatively stable association with membrane-bounded organelles in the cell. In
      addition, immunoelectron microscopy of mitochondria revealed a patch-like pattern
      in the kinesin distribution, suggesting that the organization of the motor on the
      organelle membrane may play a role in regulating organelle motility.

PMID- 1382870
TI  - Differential effect of vasoactive intestinal peptide, somatostatin, and substance
      P on human IgE and IgG subclass production.
AB  - We studied the effect of vasoactive intestinal peptide (VIP), somatostatin (SOM),
      and substance P (SP) on IL-4-stimulated human IgE and IgG subclass production.
      VIP and SOM, but not SP, inhibited IgE production without affecting IgM or IgA
      production by mononuclear cells (MNC) from nonatopic donors from 10 pM to 10 nM.
      These neuropeptides also differentially modulated IgG subclass production. While
      IgG1 production was not affected by VIP, SOM, or SP, all of the neuropeptides
      enhanced IgG2 production. By contrast, SOM and SP, but not VIP, inhibited IgG3
      production, whereas VIP and SP, but not SOM, enhanced IgG4 production. The effect
      by neuropeptides was specific since each peptide effect was specifically blocked
      by each antagonist. To achieve this effect, neuropeptides must be added at the
      start of the culture and be present throughout the entire culture period. The
      inhibition of IgE production was not mediated by known inhibitors of IgE
      production, IFN-gamma or PGE2, because the addition of anti-IFN-gamma mAb (10
      micrograms/ml) or indomethacin (0.1 microM) did not overcome the inhibition of
      IgE production. In contrast to MNC, neuropeptides did not affect IgG subclass
      production in purified B cells. IgE production was not induced by IL-4 in
      purified B cells. Neuropeptides also failed to modulate IgG subclass production
      in cultures of B cells with either T cells or monocytes. However, they modulated
      IgE production and IgG subclass production in B cells in the presence of T cells
      and monocytes. In purified B cells, IL-4 plus anti-CD40 mAb induced IgE
      production which was not inhibited by VIP or SOM. However, VIP or SOM, but not
      SP, inhibited IgE production in B cells cultured with both T cells and monocytes.
      Finally, the mechanism of modulation of IgE and IgG4 production was dependent on
      IL-4-induced switching, since neuropeptides modulated IgG4 and IgE production in
      surface IgG4-negative (sIgG4-) and sIgE- B cells, respectively. In contrast,
      modulation of IgG2 and IgG3 production was not due to switching, since
      neuropeptides did not affect either IgG2 or IgG3 production in sIgG2- or sIgG3- B
      cells, respectively.

PMID- 1382872
TI  - Effect of thapsigargin on cytosolic Ca2+ level and amylase release in rat parotid
      acinar cells.
AB  - At concentrations greater than 0.01 microM, thapsigargin (ThG) dose-dependently
      caused an increase in cytosolic free Ca2+ concentration ([Ca2+]i) in rat parotid
      acinar cells, as measured by the fluorescent Ca(2+)-indicator fura-2. In the
      absence of extracellular Ca2+, a transient increase in [Ca2+]i by ThG was
      observed, and subsequent addition of carbachol (CCh) did not produce a further
      [Ca2+]i response, suggesting that ThG released Ca2+ from the CCh-sensitive
      intracellular Ca2+ pool. Since ThG did not stimulate formation of inositol
      phosphates, the ThG-induced Ca2+ mobilization is independent of phosphoinositide
      breakdown. High concentrations (greater than 0.1 microM) of ThG induced amylase
      release from rat parotide acini, but the effect was very poor as compared with
      that of CCh or the protein kinase C activator, PMA (phorbol 12-myristate 13
      acetate). Combined addition of ThG and PMA modestly potentiated amylase release
      induced by PMA alone. These results support the view that amylase release by
      muscarinic stimulation is mediated mainly by activation of protein kinase C
      rather than a rise in [Ca2+]i, although Ca2+ may modulate the secretory response.

PMID- 1382873
TI  - Differentiation of quail myoblasts transformed with a temperature sensitive
      mutant of Rous sarcoma virus. I. Relationship between differentiation and
      tyrosine kinase of src gene product.
AB  - Quail embryonic pectoral myoblasts fuse with each other at 35.5 degrees C and 41
      degrees C to essentially equal extents. When the myoblasts were transformed with
      a temperature-sensitive mutant of Rous sarcoma virus (ts-RSV), their fusion and
      biochemical processes of differentiation became temperature-sensitive: their
      fusion occurred at 41 degrees C, the non-permissive temperature, but not at 35.5
      degrees C, the permissive temperature, suggesting that the fusion was regulated
      by the viral transforming gene. Fusion of the transformed cells proceeded more
      rapidly and synchronously than that of the parent cells at 41 degrees C, and was
      completely suppressed at the permissive temperature, unlike that of the parent
      cells. These transformed cells were used to examine the relationship between
      myogenic differentiation and the tyrosine kinase activity of the src gene
      product. In spite of the temperature sensitivity of transformation, results
      showed that expressions of the src gene at 35.5 degrees C and 41 degrees C were
      similar. However, the level of tyrosine-phosphorylated protein was decreased at
      41 degrees C. Moreover, myoblast fusion could occur at 35.5 degrees C in the
      presence of herbimycin A, an inhibitor of the tyrosine kinase activity of the src
      gene product. These results indicate that the tyrosine kinase activity of the src
      gene product is closely associated with regulation of myogenic differentiation of
      the cells.

PMID- 1382874
TI  - [Results of surgical treatment of Fallot's disease during a 5-year period (1986
      1990)].
AB  - The authors treated in the Centre for cardiovascular and transplantation surgery
      in Brno between January 1986 and September 1990 84 children with the tetralogy of
      Fallot. In 77 children a radical correction was made, in 7 children a modified B
      T anastomosis was established. Soon after the radical operation four children
      died (5.1%), soon after the palliative operation 2 children (28%). When selecting
      the type of surgery the authors take into account the clinical status of the
      child, the frequency of hypoxic episodes and anatomical conditions of the heart.
      In the authors opinion the optimal time for operation is toddler and preschool
      age. For diagnosis of the defect and postoperative evaluation in the majority of
      patients echocardiographic examination suffices, in extreme forms of the defect
      with associated defects and in patients where examination is difficult
      catheterization of the heart is necessary. In children before radical surgery
      selective coronagraphy is performed. In 87% of radically operated children the
      haemodynamic results are very good, 5% of the children have a medium severe
      residual defect and 3% of the children must undergo another operation.

PMID- 1382875
TI  - Transfer of exogenous macromolecules from rat stomach wall to blood and lymph is
      dependent on molecular weight.
AB  - Transfer selectivity to the blood and the lymph of exogenous dextrans of various
      average molecular weight (approximate 4, 10, 18, 39 and 70 kilodaltons (kDa))
      after dosing to the subserosal layer of the rat stomach wall was investigated by
      measuring the fluorescein isothiocyanate labelled dextran concentrations in the
      lymph of the thoracic duct and the peripheral plasma. The lymph/plasma level
      ratio of the dextrans rose greatly with the increase in molecular weight (over
      10kDa) owing largely to the lower plasma concentration, although the lymph levels
      of small dextran (4kDa) were not significantly higher than the plasma levels.
      These results indicate that there is an inverse relation between plasma levels of
      dextrans and their molecular weight, and also suggest that the molecular weight
      threshold of transfer selectivity of dextran to the blood and the lymph
      administered in the rat stomach wall is between 4-10 kDa.

PMID- 1382876
TI  - Inhibitory effects of some natural products on the activation of hyaluronidase
      and their anti-allergic actions.
AB  - The anti-allergic drugs disodium cromoglycate (DSCG) and tranilast are strong
      inhibitors of hyaluronidase. In the development of new anti-allergic drugs, we
      studied the inhibitory effects of some natural products on the activation of
      hyaluronidase. Among the compounds tested, liquiritigenin, isoliquiritigenin and
      baicalein showed dose-related inhibitory effects. Anti-allergic activities of
      these compounds were evident from the facts that they inhibited the histamine
      release from rat peritoneal exudate cells induced by antigen, compound 48/80 and
      calcium ionophore A-23187, and from their inhibitory effect on Shultz-Dale
      reaction using sensitized guinea pig ileum.

PMID- 1382877
TI  - [A modified staining method for examining Y chromatin].
AB  - A modified staining method for Y chromatin is reported here which proved to be
      rapid and efficient for sex differentiation diagnosis. Samples were fixed in
      methanol: acetic acid (3:1) solution and stained with dyes in McIlvaine buffer. Y
      chromatin in buccal smears from normal males could be clearly revealed by this
      method. With this modified method and X-chromatin examination, one testicular
      feminization was found during examination of 1342 athletes for the 11th Asian
      Games.

PMID- 1382878
TI  - [Transitory postoperative anuria after transvesical prostatic adenomectomy:
      review of the literature, description of new clinical cases and
      physiopathological considerations].
AB  - Anuria is a rare complication after prostate adenomectomy. Three cases of
      complete bilateral anuria and one case of monolateral anuria are reported
      following transvesical prostate adenomectomy, characterized by immediate onset
      without any apparent cause and by spontaneous resolution within 48 hours. After a
      thorough review of the literature, the authors analyze the pathophysiological and
      clinical aspects of post-prostate-adenomectomy anuria and postulate an
      "obstructive" aetiology for the anuria cases observed in their series.

PMID- 1382879
TI  - Clinical and pharmacokinetic aspects of the combination of meperidine and
      prilocaine for spinal anaesthesia.
AB  - The aim of this study was to determine whether the addition of a small dose of
      prilocaine could augment the spinal block induced by meperidine and affect
      intrathecal meperidine pharmacokinetic behaviour. Spinal anaesthesia was
      performed in 60 men scheduled for endoscopic resection of a prostatic adenoma or
      bladder tumour under spinal anaesthesia. They were allocated randomly to receive
      either 1 mg.kg-1 meperidine (Group 1, n = 30), or 1 mg.kg-1 meperidine plus 0.5
      mg.kg-1 prilocaine (Group 2, n = 30). Blood samples were collected prior to and
      for 24 hr after spinal injection in 24 patients (12 in each group). Plasma
      meperidine levels were assayed by gas chromatography. Complete motor block was
      achieved in all Group 2 patients, but was incomplete in seven of Group 1 (P less
      than 0.05). The onset of both motor and sensory blocks was shorter (P less than
      0.01) in Group 2 and the duration was longer (P less than 0.05). Coadministration
      of prilocaine modifies meperidine pharmacokinetic behaviour. The area under curve
      was 48% greater (P less than 0.01) and Cmax was higher in Group 2 than in Group
      1, 145.8 +/- 42.2 vs 107 +/- 20.5 ng.ml-1 (P less than 0.001). No evidence of
      respiratory depression was noted in any of the patients. Despite the increase in
      plasma meperidine concentrations, no side effects were observed. The plasma
      concentrations remained at one third to one sixth the levels reported to induce a
      respiratory depression. It is concluded that the addition of prilocaine to
      meperidine improves motor and sensory block during surgery and alters meperidine
      kinetics without producing major side effects.

PMID- 1382880
TI  - Nonimmunological release of histamine from rat mast cells elicited by
      antineoplastic agents: effect of drug combinations.
AB  - We studied the release of histamine elicited by some antineoplastic drugs in rat
      pleural and peritoneal mast cells. The drugs tested included the antibiotic
      mitomycin; the anthracyclines daunorubicin, doxorubicin, and epirubicin; the
      glycopeptide bleomycin; the chromopeptide dactinomycin; the platinum coordination
      complexes carboplatin and cisplatin; and the anthracenedione mitoxantrone.
      Mitomycin and bleomycin failed to elicit any release of histamine, whereas all of
      the other drugs induced histamine release from either pleural or peritoneal mast
      cells, the release being independent of extracellular calcium. The results
      indicate that antineoplastic drugs activate histamine release in a manner similar
      to that shown by compound 48/80, which may contribute to some of their secondary
      effects.

PMID- 1382881
TI  - Drug resistance in cultured rat liver epithelial cells spontaneously and
      chemically transformed.
AB  - Cultured rat liver epithelial cells (RLE) transformed with repeated treatments of
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) demonstrate many features of the
      common biochemical phenotype of multidrug resistance (MDR) seen in vivo in
      'resistant hepatocytes'. The cells have increased glutathione-S-transferase
      placental subunit (GST-Yp), gamma-glutamyltranspeptidase (GGT), glutathione (GSH)
      and glutathione peroxidase and are resistant to MNNG. Phenotypically identical
      RLE cells spontaneously transformed by selective culture conditions showed low
      levels of GGT and GST and were not resistant to MNNG. Both chemical and
      spontaneous transformants are cross resistant to doxorubicin although resistance
      is consistently greater in chemical transformants. No direct correlation was
      found between the degree of resistance to doxorubicin and MDR gene expression in
      either of the chemically or spontaneously transformed RLE cells. These
      observations suggest that in chemical carcinogenesis, other mechanisms of drug
      detoxification are involved and that MDR expression is not a consistent feature.

PMID- 1382882
TI  - Reactivity of monoclonal antibody E5 with endotoxin. II. Binding to short- and
      long-chain smooth lipopolysaccharides.
AB  - The murine monoclonal IgM antibody E5 has been shown to significantly reduce the
      mortality and morbidity of patients with Gram-negative sepsis in a multicenter
      randomized placebo-controlled clinical trial. The in vitro binding
      characteristics of monoclonal antibody (mAb) E5 were studied using highly
      purified smooth lipopolysaccharide (LPS) isolated from a variety of clinically
      relevant, wild-type Gram-negative bacteria. Using a sensitive antibody-capture
      assay which involves immobilized mAb E5 and a chromogenic Limulus amebocyte
      lysate (LAL) LPS-detection system, mAb E5 was shown to bind to all 15 smooth LPS
      preparations tested, including LPS isolated from Escherichia, Klebsiella,
      Proteus, Pseudomonas, Salmonella, Serratia and Yersinia species. When LPS was
      fractionated according to size by size-exclusion chromatography, mAb E5 was shown
      to bind to smooth LPS molecules that have long as well as short O-polysaccharide
      chains. These results confirm and extend those reported previously and
      demonstrate that the anti-lipid A mAb E5 binds specifically to a diverse spectrum
      of smooth LPS isolated from wild-type Gram-negative bacteria.

PMID- 1382883
TI  - Effect of perfusate [Ca2+] on cardiac sarcoplasmic reticulum Ca2+ release channel
      in isolated rat hearts.
AB  - The effect of perfusate [Ca2+] on the function of cardiac sarcoplasmic reticulum
      (CSR) was assessed by the oxalate-supported Ca2+ uptake rate of ventricular
      homogenates of isolated rat hearts maintained in a modified Langendorff
      preparation. The total Ca2+ pumping activity of the CSR was determined by using
      20 microM ruthenium red or 625 microM ryanodine to close the CSR Ca2+ release
      channel. The homogenate Ca2+ uptake rate in the absence of ruthenium red or
      ryanodine decreased progressively with increasing perfusate [Ca2+] (25.7 +/- 1.2,
      21.4 +/- 1.5, 17.2 +/- 1.1, and 16.3 +/- 1.2 [mean +/- SEM] nmol Ca2+.min-1.mg-1
      for hearts perfused for 5 minutes with 0.2, 1.4, 2.8, and 5.6 mM Ca2+,
      respectively; p = 0.0001; n = 8). This depression was not observed when Ca2+
      uptake was assayed in the presence of ryanodine or ruthenium red. Since the Ca2+
      uptake in the presence of ryanodine or ruthenium red is determined by the Ca(2+)
      ATPase, this result suggests that perfusion with varying [Ca2+] did not affect
      the Ca(2+)-ATPase. The observed decrease in Ca2+ uptake in the absence of
      ryanodine or ruthenium red is caused by an increased efflux through the ryanodine
      sensitive Ca2+ release channel. When hearts perfused for 5 minutes with 0.2 or
      5.6 mM Ca2+ were reperfused for 10 minutes with 1.4 mM Ca2+, homogenate Ca2+
      uptake rates were restored to near control levels. These effects of perfusate
      Ca2+ were not direct effects, because changes in the [Ca2+] of the homogenization
      medium did not alter the homogenate Ca2+ uptake activity in either the presence
      or absence of ryanodine. The homogenate Ca2+ uptake rates were unaffected by
      prior active loading of the CSR with Ca2+. These results suggest a regulatory
      role of perfusate Ca2+ in increasing the open state of the ryanodine-sensitive
      Ca2+ release channel that is distinct from the beat-to-beat regulation of Ca2+
      release from the CSR by Ca2+ (Ca(2+)-induced Ca2+ release).

PMID- 1382884
TI  - Multiple connexins confer distinct regulatory and conductance properties of gap
      junctions in developing heart.
AB  - Multiple gap junction proteins (connexins) and channels have been identified in
      developing and adult heart. Functional expression of the three connexins found in
      chick heart (connexin42, connexin43, and connexin45) by stable transfection of
      communication-deficient neuro2A (N2A) cells revealed that all three connexin
      cDNAs are capable of forming physiologically distinct gap junctions that differ
      in their transjunctional voltage dependence and unitary channel conductances. The
      transjunctional voltage dependences of connexin45 and connexin42 closely
      resembled those of 4-day and 18-day embryonic chick heart gap junctions,
      respectively. The multiple channel conductances between 80 and 240 pS, including
      the predominant 160 pS channel, observed in embryonic chick heart were also
      common to connexin42. The expression of multiple gap junction channels with
      distinct conductance and regulatory properties within a given tissue may account
      for developmental changes in intercellular communication.

PMID- 1382885
TI  - [An improvement of liver egg-immunoenzymatic staining technique for diagnosis of
      schistosomiasis japonica].
AB  - Using PVC membrane instead of common slide in liver egg-immunoenzymatic staining
      technique (IEST) for diagnosis of schistosomiasis japonica to detect specific
      antibodies in sera from 179 cases with schistosomiasis japonica, the positive
      rate was 97.2% (174/179). Sera from 63 healthy individuals revealed in one
      positive (1.5%). No cross reaction was observed in sera from 6 cases of
      paragonimiasis. PVC-IEST and SLIDE-IEST were comparatively performed on sera from
      78 cases with schistosomiasis japonica, the positive rates were 96.2% (75/78) and
      97.4% (76/78), respectively (P greater than 0.05). As PVC-IEST is simpler to
      perform than SLIDE-IEST, it is suggested that the former is more suitable for
      application in the field for diagnostic purposes.

PMID- 1382886
TI  - [Studies on antigenic homology between Schistosoma japonicum and Oncomelania
      hupensis hupensis by indirect immunoperoxidase technique].
AB  - Adult Schistosoma japonicum worms and Oncomelania hupensis hupensis tissue
      sections were employed as antigens in the studies of anti-O. h. hupensis rabbit
      serum and anti-S. japonicum adult worm rabbit serum by indirect immunoperoxidase
      assay. The result indicated that the most prominent peroxidase reaction was
      presented in the adult worm sections and the head-foot and liver sections of O.
      h. hupensis. These suggested the possible presence of antigenic homology between
      Schistosoma japonicum and Oncomelania hupenis hupensis. (Figs. 1-7).

PMID- 1382887
TI  - Deficient acceleration of left ventricular relaxation during exercise after heart
      transplantation.
AB  - BACKGROUND: The exercise-induced rise in left ventricular filling pressures after
      cardiac transplantation is considered to be the result of a blunted heart rate
      response, of elevated venous return, and of unfavorable passive late-diastolic
      properties of the cardiac allograft. In contrast to passive late-diastolic left
      ventricular properties, the effect of left ventricular relaxation on the exercise
      induced rise in left ventricular filling pressures of the cardiac allograft has
      not yet been studied. In the present study, the response of left ventricular
      relaxation to exercise was investigated in transplant recipients and compared
      with left ventricular relaxation observed in normal control subjects exercised to
      the same heart rate. Moreover, the response of left ventricular relaxation of the
      cardiac allograft to beta-adrenoreceptor stimulation, to reduced left ventricular
      afterload, and to increased myocardial activator calcium was investigated by
      infusion of dobutamine and of nitroprusside and by postextrasystolic
      potentiation. METHODS AND RESULTS: Twenty-seven transplant recipients were
      studied 1 year (n = 17), 2 years (n = 7), 3 years (n = 2), and 4 years (n = 1)
      after transplantation. All patients were free of rejection and of significant
      graft atherosclerosis at the time of study. Tip-micromanometer left ventricular
      pressure recordings and cardiac hemodynamics were obtained at rest, during supine
      bicycle exercise stress testing (n = 27), during dobutamine infusion at a heart
      rate matching the heart rate at peak exercise (n = 8), during nitroprusside
      infusion (n = 9), and after postextrasystolic potentiation (n = 10). Tip
      micromanometer left ventricular pressure recordings were also obtained in a
      normal control group (n = 9) at rest and during supine bicycle exercise stress
      testing to a heart rate, which matched the heart rate of the transplant recipient
      group at peak exercise. Left ventricular relaxation rate was measured by
      calculation of a time constant of left ventricular pressure decay (T) derived
      from an exponential curve fit to the digitized tip-micromanometer left
      ventricular pressure signal. In the transplant recipients, exercise abbreviated T
      from 43 +/- 6 to 40 +/- 8 msec (p less than 0.01) and caused a rise of left
      ventricular minimum diastolic pressure (LVMDP) from 5 +/- 2 to 9 +/- 6 mm Hg (p
      less than 0.001). In normal control subjects, exercise induced a 2.5 times larger
      abbreviation of T (from 42 +/- 7 to 34 +/- 6 msec; p less than 0.001) and a small
      drop in LVMDP from 5 +/- 2 to 4 +/- 3 mm Hg (p less than 0.05). In the transplant
      recipients, the change in T (delta T) from rest to exercise was variable ranging
      from an abbreviation, as observed in normal controls, to a prolongation and was
      significantly correlated with the change in RR interval (delta RR) and the change
      in left ventricular end-diastolic pressure (delta LVEDP) (delta T = 0.068 delta
      RR + 0.58 delta LVEDP-2.2; r = 0.76; p less than 0.001). In a first subset of
      transplant recipients (n = 8), dobutamine infusion resulted in a heart rate equal
      to the heart rate at peak exercise, a left ventricular end-diastolic pressure (8
      +/- 7 mm Hg) lower than at peak exercise (22 +/- 6 mm Hg; p less than 0.05) and a
      T value (32 +/- 9 msec), which was shorter than both resting value (44 +/- 5
      msec; p less than 0.005) and value observed at peak exercise (40 +/- 8 msec; p
      less than 0.01). In a second subset of transplant recipients (n = 9),
      nitroprusside infusion and postextrasystolic potentiation resulted in a
      significant prolongation of T from 41 +/- 7 to 56 +/- 10 msec (p less than 0.05)
      and a characteristic negative dP/dt upstroke pattern with downward convexity as
      previously observed in left ventricular hypertrophy. CONCLUSIONS: Exercise after
      cardiac transplantation resulted in a smaller acceleration of left ventricular
      relaxation than in a normal control group exercised to the same heart rate...

PMID- 1382888
TI  - New findings concerning ventricular septation in the human heart. Implications
      for maldevelopment.
AB  - BACKGROUND: The mechanics involved in development of the inlet component of the
      morphologically right ventricle are, as yet, undecided. Some argue that this
      component is derived from the descending limb of the ventricular loop, and that
      the inlet and apical trabecular components of the muscular ventricular septum
      have separate developmental origins. Others state that the entirety of the right
      ventricle grows from the ascending limb of the loop, and that the muscular
      septum, apart from its outer component, has a unitary origin. We now have
      material from human embryos at our disposal, which, we believe, solves this
      conundrum. METHODS AND RESULTS: We used a monoclonal antibody against an antigen
      to neural tissue from the chick to demarcate a ring of cells separating the
      descending (inlet) and ascending (outlet) limbs of the developing ventricular
      loop of the human heart. Preparation of serial sections of graded human embryos
      enabled us to trace the fate of this ring, and hence the formation of the inlet
      of the right ventricle, to the completion of cardiac septation. Eight embryos
      were studied, encompassing stages 14-23 of the Carnegie classification. The ring
      of cells initially separating the ascending and descending limbs of the
      ventricular loop were, at the conclusion of ventricular septation, located within
      the atrioventricular junction, sequestrated for the most part in the terminal
      segment of atrial myocardium. CONCLUSIONS: Our study conclusively shows that the
      inlet component of the morphologically right ventricle is derived from the
      ascending limb of the embryonic ventricular loop, and that the inlet and apical
      trabecular components of the muscular septum are derived from the same primary
      ventricular septum.

PMID- 1382889
TI  - Postextrasystolic potentiation and its contribution to the beat-to-beat variation
      of the pulse during atrial fibrillation.
AB  - BACKGROUND: Beat-to-beat variations in the pulse during atrial fibrillation (AF)
      have conventionally been attributed to time-dependent changes in filling. We have
      explored the possibility that they are dependent on the intrinsic myocardial
      interval force relation. METHODS AND RESULTS: Left ventricular (LV) contractility
      (maximum rate of rise of pressure, LV dP/dtmax) and ascending aortic blood
      velocity were measured during cardiac catheterization in 15 patients with AF.
      Beats preceded by an interval of less than 500 msec were excluded from analysis
      to reduce the confounding influence of incomplete mechanical restitution. The LV
      dP/dtmax was then related to the prepreceding interval. An inverse relation
      consistent with postextrasystolic potentiation was obtained in all 15 patients
      (Spearman's rank correlations, -0.56 to -0.86; p less than or equal to 0.0001).
      This relation was confirmed in three patients during pacing that overrode the AF
      and introduced single-interval variations into steady-state pacing. The ECG
      sequences from six of the AF patients were used to drive isometrically
      contracting guinea pig papillary muscle and human right ventricular tissue (n =
      7); the same inverse relation was demonstrated. On a beat-by-beat basis, the
      maximum rate of rise of force in the isolated muscle correlated well with LV
      dP/dtmax in the patients (r = 0.50-0.86, p less than or equal to 0.0001). The
      relation of the integral of aortic velocity (AVI, proportional to stroke volume)
      to prepreceding interval was also inverse, whereas important correlations were
      demonstrated between LV dP/dtmax and AVI (Spearman's rank correlations, 0.27
      0.95; p less than or equal to 0.0001). CONCLUSIONS: This study demonstrates that
      postextrasystolic potentiation contributes to the characteristic beat-to-beat
      variation of the pulse in AF.

PMID- 1382890
TI  - [The effect of acupuncture on the content of substance P in serum of gravida
      during delivery].
AB  - We determined the content of substance P in the serum of 56 gravida with
      radioimmunoassay before and after acupuncture during the active period of the
      delivery. The result suggested that the acupuncture may be decline the content of
      substance P in the serum of the gravida, so that played role of analgesic
      effects.

PMID- 1382891
TI  - The origins of supraspinal projections to the cervical and lumbar spinal cord at
      different stages of development in the gray short-tailed Brazilian opossum,
      Monodelphis domestica.
AB  - We have used the retrograde transport of Fast blue (FB) to study the origins of
      supraspinal projections to the lumbar and cervical spinal cord at different
      stages of development in the Brazilian, short-tailed opossum, Monodelphis
      domestica. Monodelphis was chosen for study because its young are born in a very
      immature state, 14-15 days after copulation, making it possible to manipulate its
      nervous system in an embryonic state without intra-uterine surgery. When
      injections of FB were made into the lumbar cord at postnatal day (PD) 1, neurons
      were labeled within several areas of the reticular formation (the retroambiguus
      nucleus, the ventral and dorsal reticular nuclei of the medulla, the
      gigantocellular reticular nucleus, the lateral paragigantocellular reticular
      nucleus, and the pontine reticular nucleus), the presumptive coeruleus complex,
      and the lateral vestibular nucleus. In many cases, labeled neurons were also
      found within the caudal raphe and the presumptive interstitial nucleus of the
      medial longitudinal fasciculus. The results of immunocytochemical studies
      provided evidence for catecholaminergic and serotoninergic neurons in the
      brainstem at PD1 and for axons of both phenotypes in the spinal cord. By PD3,
      labeled neurons were found within the ventral gigantocellular and ventral pontine
      nuclei of the reticular formation, the spinal trigeminal nucleus, and the
      presumptive paraventricular nucleus of the hypothalamus. When injections were
      made at PD4, neurons were also labeled within the medial and inferior vestibular
      nuclei, the red nucleus, the mesencephalic nucleus of the trigeminal nerve, the
      presumptive nucleus of Edinger-Westphal and the lateral hypothalamus. By at least
      PD7, the pattern of supraspinal labeling was similar to that obtained at older
      ages and in the adult animal. When FB was injected into the cervical cord at PD1,
      neurons were labeled in all of the areas labeled by lumbar injections at the same
      age and in larger numbers. In addition, labeled neurons were found within the
      ventral gigantocellular and spinal trigeminal nuclei. When cervical injections
      were made at PD15, labeled neurons were found within the deep cerebellar nuclei
      and amygdala and by PD17 they were also present within the superior colliculus
      and cerebral cortex. In some cases, cortical labeling was present outside the
      areas labeled by comparable injections in adult animals.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1382892
TI  - Monoclonal antibodies which stain small subsets of neurons in the Drosophila
      central nervous system.
AB  - Monoclonal antibodies (MAbs) specific to small subsets of neurons in the central
      nervous system (CNS) of Drosophila melanogaster were described. MAbs 43A8, 45C6
      and 65C11, which were obtained in fusion experiments using the third instar
      larval or prepupal CNS as an immunogen, stained a small number of neurons in the
      postembryonic CNS. Functional implications of the observed immunoreactivities
      during neural development in the Drosophila CNS are discussed.

PMID- 1382893
TI  - Prostate-specific antigen comes of age in diagnosis and management of prostate
      cancer.

PMID- 1382894
TI  - Concentrations of human choriogonadotropin, its beta-subunit, and the core
      fragment of the beta-subunit in serum and urine of men and nonpregnant women.
AB  - Sensitive, specific time-resolved immunofluorometric assays were used to measure
      the concentrations of human choriogonadotropin (hCG), free beta-subunit (beta
      hCG), and the core fragment of beta-hCG (c beta-hCG) in serum and urine of men
      and nonpregnant women without evidence of cancer. Concentrations of hCG and beta
      hCG were measurable in 59-70% of serum samples and in 50-59% of urine samples. c
      beta-hCG was mostly undetectable in serum but measurable in 81% of urine samples.
      Concentrations were higher in women than in men, and hCG concentrations increased
      with age. Therefore, reference ranges based on the 97.5 percentile were
      calculated separately for women and men and for those < 50 and > 50 years.
      However, concentrations of hCG correlated much more strongly with those of
      follicle-stimulating hormone than with age. hCG concentrations in serum were
      similar to those reported before, but beta-hCG concentrations were below the
      detection limit of earlier assays, and the upper reference limit was one-fifth to
      one-tenth the cutoff concentrations used earlier. In urine, hCG and c beta-hCG
      were the major forms of hCG, and their concentrations were similar to those of
      hCG in serum.

PMID- 1382895
TI  - Determination of fetal hemoglobin by time-resolved immunofluorometric assay.
AB  - We have developed a "sandwich"-type time-resolved immunofluorometric assay (IFMA)
      for fetal hemoglobin (HbF) in hemolysates from adults and newborns, amniotic
      fluid, and plasma, based on a polyclonal and a monoclonal antibody against human
      fetal hemoglobin. Microtiter wells are coated with polyclonal capture antibody,
      and the gamma-chain-specific monoclonal tracer antibody is labeled with a
      europium chelate. In a simple and fast assay procedure, prediluted hemolysates
      are incubated in the microtiter wells first with capture antibody for 1 h and,
      after washing, for 1 h with tracer antibody. The wells are washed and the
      fluorescence of europium is measured. The mean analytical recovery is 102% and
      results by IFMA agreed well with values obtained by high-performance liquid
      chromatography. The analytical range of IFMA is large and well suited for
      clinical purposes. The detection limit of the assay is 0.2 microgram/L and the
      measuring range extends to 500 micrograms/L.

PMID- 1382896
TI  - Specific and sensitive measurement of FK506 and its metabolites in blood and
      urine of liver-graft recipients.
AB  - A specific and sensitive assay for quantifying the immunosuppressant FK506 and
      its metabolites in blood and urine was developed. 32-O-Acetyl FK506 was
      synthesized and used as internal standard. FK506 and its metabolites were
      purified from the samples by solid-liquid extraction and were injected into a
      high-performance liquid chromatographic (HPLC) system linked to a mass
      spectrometer (MS) by particle-beam interface. The FK506 derivatives were
      separated from interfering material by use of a 100 x 4 mm C8 analytical column
      and water/acetonitrile or water/methanol gradient elution; they were detected by
      negative chemical ionization with methane as reagent gas. The limit of detection
      was 25 pg in a standard solution, and the limit of quantification in blood was
      250 pg (extracted from 1 mL of blood). The CV was 11.3% at 5 ng, and no
      interferences with other drugs were found.

PMID- 1382897
TI  - Evaluation of the Abbott IMx automated immunoassay of prostate-specific antigen.
AB  - We detail the performance characteristics of the new IMx PSA immunoassay
      developed by Abbott Laboratories, addressing PSA recovery, assay reproducibility,
      standard curve storage, lower limit of detection, dilution linearity, and
      correlation with the Hybritech Tandem-R PSA immunoassay. We analyzed 686 sera for
      PSA retrospectively, testing 555 of these concurrently with the IMx and the
      Tandem-R immunoassays. The IMx PSA standard curve was linear from 0 to 100
      micrograms/L, and curve storage was maintained for 4 weeks. The lower limit of
      detection of the IMx PSA assay was < or = 0.03 microgram/L; allowing for the
      assay precision yielded a biological detection limit of 0.06 microgram/L. We
      conservatively set the clinical threshold at 0.1 microgram/L. Regression analysis
      of dilution linearity involving 10 samples (0.44-200 micrograms/L) resulted in
      coefficients of correlation ranging from 0.9972 to 1.000. Reproducibility studies
      with 18 specimens within the range of 0.39-413.67 micrograms/L gave intra- and
      interassay CVs < 6.5%. The interassay 95% confidence interval for a specimen
      containing 0.06 microgram of PSA per liter was 0.03-0.09 microgram/L. Correlation
      between IMx and Tandem-R PSA assay results was excellent: r = 0.9909 and slope =
      0.95. Overall, the IMx PSA immunoassay, with the conveniencies of automation,
      curve storage, and nonisotopic handling, provided an improved lower limit of PSA
      detection, which allows for earlier indication of residual or recurrent disease
      after radical prostatectomy.

PMID- 1382899
TI  - Reporting cumulative results provides precise quality control for alpha
      fetoprotein assays.

PMID- 1382898
TI  - Abbott IMx evaluated for assay of prostate-specific antigen in serum.
AB  - We evaluated a new fully automated procedure for quantitative measurement of
      prostate-specific antigen (PSA) by the Microparticle Enzyme Immunoassay (MEIA)
      technology developed for the Abbott IMx automated immunoassay system. The
      performance characteristics of the Abbott IMx PSA assay (y) were evaluated and
      compared with those of the Hybritech Tandem-E PSA assay (x), a solid-phase two
      site immunoenzymometric assay. PSA values for both assays were well correlated (r
      = 0.99); regression analysis yielded the equation y = 0.92x - 0.23 micrograms/L.
      The Abbott assay proved reliable and reproducible, as shown by the intra- and
      interassay coefficients of variation (2.0-3.4% and 3.1-4.7%, respectively). The
      assay gave a linear standard curve up to 100 micrograms/L and was very sensitive
      (detected PSA < 0.1 microgram/L). This analytical sensitivity was comparable with
      that of the Tandem-E PSA assay. Overall, the IMx PSA assay demonstrated the
      accuracy, precision, linearity, and intermethod correlation required for
      monitoring patients with prostate cancer.

PMID- 1382900
TI  - A colorimetric determination of 5-hydroxyindole acetic acid in urine.

PMID- 1382901
TI  - Increased urinary excretion of coproporphyrin isomers after transcatheter
      arterial embolization of hepatocellular carcinoma.

PMID- 1382902
TI  - Renal allograft rejection: induction and function of adhesion molecules on
      cultured epithelial cells.
AB  - The interaction of graft-infiltrating immune cells with donor parenchymal cells
      is an important early event in allograft rejection. This binding is stabilized by
      interaction of antigen-independent 'adhesion' molecules expressed on the two cell
      types. As the level of expression of these molecules can be altered during
      inflammation, a series of experiments was performed to examine the effects of the
      inflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor
      alpha (TNF-alpha) on adhesion molecules expressed by cultured human renal tubular
      epithelial cells. These cells constitutively expressed ICAM-1 and LFA-3.
      Incubation with IFN-gamma increased expression of ICAM-1 but had no significant
      effect on expression of LFA-3 (P greater than 0.05). Incubation with TNF-alpha
      increased expression of both ICAM-1 and LFA-3; IFN-gamma synergized with TNF
      alpha to further augment expression of these molecules. Peripheral blood
      lymphocytes (PBL) showed an enhanced binding to allogeneic renal epithelial cell
      monolayers which had been pretreated with IFN-gamma or TNF-alpha. MoAbs specific
      for ICAM-1 or its ligand LFA-1 inhibited adhesion of PBL to either IFN-gamma- or
      TNF-alpha-pretreated renal cells. By contrast, antibodies specific for LFA-3 or
      its ligand CD2 only significantly blocked PBL adhesion to renal cells which had
      been pretreated with TNF-alpha. Combination of antibodies specific for multiple
      components of the adhesion systems produced greater inhibition of adhesion than
      was produced by any single MoAb. These results suggest that the inflammatory
      cytokines IFN-gamma and TNF-alpha up-regulate expression of functional ICAM-1 and
      LFA-3 molecules which can augment the binding of potentially graft-damaging
      lymphoid cells to renal tubular epithelial cells.

PMID- 1382904
TI  - The role of O-antigen polysaccharide in the activation of neutrophils by
      lipopolysaccharides of Salmonella species.
AB  - Activation of neutrophils by lipid A, O-antigen polysaccharides (PS) and smooth
      lipopolysaccharides (LPS) isolated from Salmonella choleraesuis (O-6,7) and
      Salmonella typhimurium (O-4,5,12) was investigated. The methods used were assays
      for lysozyme release and for nitroblue tetrazolium (NBT) reduction which measures
      the level of oxidative metabolism of neutrophils. LPS from both species
      stimulated neutrophils to the same extent in the presence of autologous plasma.
      In the absence of plasma only the O-6,7 LPS activated neutrophils. Lipid A or PS
      isolated from both LPS either did not activate neutrophils or did so only at very
      high concentrations when tested in the presence of plasma; in the absence of
      plasma no activation occurred. The data indicate that both PS and lipid A
      segments of LPS are required for activation of neutrophils by LPS. We also deduce
      that plasma, probably complement, is required for the interaction of some LPS,
      e.g. O-4,5,12 with neutrophils whereas other LPS, e.g. O-6,7 can interact
      directly and activate neutrophils.

PMID- 1382903
TI  - IL-2 regulation of soluble IL-2 receptor levels following thermal injury.
AB  - In the immunosuppressed burn patient serum levels of both IL-2 and a soluble form
      of IL-2 receptor alpha (sIL-2R alpha) are significantly elevated. Strikingly, the
      production of these markers by the in vitro activated patients' cells is
      decreased. This study examines the role of IL-2 in the decreased production of
      the sIL-2R alpha in vitro in patients with major burns (n = 18, 30 to greater
      than 70% total body surface area). Peripheral blood mononuclear cell (PBMC)
      cultures from patients with highly elevated serum sIL-2R alpha, and from healthy
      controls (n = 12) were activated with concanavalin A (Con A) at initiation. In
      patients' cultures mitogen-induced increments of sIL-2R alpha levels were
      significantly lower. There was a significant negative correlation (r = 0.64, P
      less than 0.001) between a high serum sIL-2R alpha level and a decreased lectin
      induced sIL-2R alpha release in vitro. Low levels of sIL-2R alpha in patients'
      samples were not normalized by increasing the number of T lymphocytes. Also
      exogenous rIL-1 was without effect, whereas rIL-3 increased sIL-2R alpha release
      in some cultures. However, sIL-2R alpha levels were significantly increased in
      patients' cultures by (i) addition of exogenous IL-2; (ii) removal of adherent
      cells; (iii) addition of cyclooxygenase inhibitor, indomethacin; (iv) bypassing
      cell surface activation by the combination of the calcium ionophore A23187 and
      the phorbol ester 12-o-tetradecanoyl acetate. The cyclic AMP-elevating drug,
      forskolin, abrogated the ability of exogenous IL-2 to increase sIL-2R alpha
      production. Thus, in the burn patient, the reduced in vitro sIL-2R alpha release
      appears to relate to abnormalities in IL-2 production and action mediated through
      its functional surface receptor. Elevated levels of sIL-2R alpha in vivo may,
      therefore, reflect systemic activation of T lymphocytes in response to
      biologically active IL-2.

PMID- 1382905
TI  - Absence of circulating interferon in patients with inflammatory bowel disease.
      Suggestion against an autoimmune etiology.
AB  - Whether inflammatory bowel diseases (IBD) can be classified as autoimmune
      disorders is not established. Since circulating acid-labile interferon-alpha (IFN
      alpha) is believed to reflect autoimmune reactions, we tested sera from two
      groups of IBD patients for the presence of circulating IFN. No detectable IFN was
      found in 51 serum samples of IBD patients. Furthermore, in no serum sample of IBD
      patients were neutralizing anti-IFN antibodies found. In contrast, acid-labile
      IFN-alpha was present in sera from 21/52 HIV-infected and from 6/14 systemic
      lupus erythematosus patients. These observations provide evidence that IBD
      differs from systemic autoimmune disorders, at least for the presence of
      circulating IFN.

PMID- 1382906
TI  - Antigen-specific T cell recognition of affinity-purified and recombinant thyroid
      peroxidase in autoimmune thyroid disease.
AB  - The T cell proliferative responses of peripheral blood lymphocytes from 20
      patients with autoimmune thyroid disease (AITD) and 20 healthy controls were
      analysed to immunoaffinity-purified thyroid peroxidase (TPO) and recombinant
      antigen preparations generated in Escherichia coli as glutathione-s-transferase
      fusion proteins. The epitope specificity of the T cell response was investigated
      using a selection of eight discrete recombinant fragments encompassing the whole
      of the extracellular region of the TPO molecule. Significant differences in the
      proliferative responses between patients and controls were observed to the full
      length, affinity-purified TPO molecule (P less than 0.002) as well as to the
      recombinant fragments R1c (residues 145-250) (P less than 0.001) and R2b
      (residues 457-589) (P less than 0.001) suggesting the presence of at least two
      distinct T cell determinants on this autoantigen. One of these T cell epitopes,
      localized within the region R1c, has not previously been identified by studies
      with synthetic peptides.

PMID- 1382907
TI  - Studies on the effect of dopamine on the human platelet response.
AB  - 1. The present study investigated the in vitro effect of dopamine on platelet
      responses in healthy subjects. 2. Dopamine concentrations over 5 mumol/L induced
      a primary aggregating response and a slight release of alpha-granule proteins,
      beta-thromboglobulin and platelet factor-4 in all subjects. In 25% of
      investigated subjects a delayed secondary aggregation was observed with dopamine
      concentrations over 100 mumol/L. 3. Low dopamine concentrations (5-7.5 nmol/L)
      increased the platelet sensitivity to other aggregating agents (adenosine
      diphosphate, collagen and sodium arachidonate). The effect of subaggregating
      concentrations of serotonin was potentiated by dopamine. 4. The effect of
      dopamine on platelet responses was prevented by low concentrations of alpha
      adrenoceptor antagonists (phentolamine and yohimbine); antagonists of dopamine
      receptors (haloperidol and domperidone) were able to decrease the extent of the
      dopamine-induced secondary aggregating wave in the responders, but they failed to
      prevent the primary aggregation and the effects on platelet response to other
      aggregating agents. 5. The present data demonstrated that the effects of dopamine
      on human platelets are mainly mediated by interactions with alpha-adrenoceptors.

PMID- 1382908
TI  - IL-10 production in a CD5+ B cell lymphoma arising in a CD4 monoclonal antibody
      treated SJL mouse.
AB  - A majority of SJL mice develop spontaneous reticulum cell sarcomas (RCS) at about
      1 year of age which can be transplanted into young SJL recipients. Previous
      studies have shown that RCS tumors are of B cell lineage, and that the
      development of these lymphomas and their subsequent growth depends upon host
      derived T helper cell factors. In vivo treatment of SJL mice with anti-CD4
      monoclonal antibody (mAb) prevents the development of the characteristic B
      lymphomas. Most of the mAb-treated animals were tumor free and had a
      significantly prolonged life span. However, one such CD4 mAb-treated mouse
      developed a transplantable IgM+ CD5+ B cell lymphoma (designated NJ101), which
      has not previously been described in SJL/J mice. NJ101 is clonal on the basis of
      a discrete non-germ line Ig heavy chain gene rearrangement by Southern blot
      analysis. Unlike the sIg- CD5- transplantable RCS-X cell line, the IgM+ CD5+
      NJ101 lymphoma cells will grow in immuno-compromised hosts, such as irradiated
      recipients or in recipients treated with CD4 mAb in vivo. The RCS (B cell)
      lymphoma requires CD4+ T cells for progressive growth, whereas the growth of the
      CD5+ B lymphoma cells is enhanced by the removal of such cells. Thus, CD5+ B cell
      clonal development may be aided by the removal of regulatory T cells and/or the
      malignant CD5+ B cells may produce their own growth factors in an autocrine
      manner. Examination of IL-10 message by quantitative polymerase chain reaction
      techniques indicate that the CD5+ B lymphoma cells produce increased levels of IL
      10 relative to normal LN cells or purified RCS lymphoma cells. These results
      suggest that two different types of B cell tumors, both of which can develop in
      SJL mice, have different growth requirements. Furthermore, treatment to prevent
      the occurrence of the characteristic RCS malignancy of SJL mice may lead to the
      development of another form of B cell neoplasia.

PMID- 1382909
TI  - Increased levels of beta 2-microglobulin, soluble interleukin-2 receptor, and
      soluble CD8 in patients with subacute sclerosing panencephalitis.
AB  - We measured beta 2-microglobulin (beta 2-M), soluble interleukin-2 receptor (sIL
      2R), and soluble CD8 (sCD8) antigen levels in paired cerebrospinal fluid (CSF)
      and sera from patients with subacute sclerosing panencephalitis (SSPE), multiple
      sclerosis (MS), and other neurological diseases (OND) using enzyme-linked
      immunosorbent assay. beta 2-M was significantly increased in CSF of the SSPE
      group compared to the MS or the OND group. Similarly, beta 2-M in the MS versus
      OND group was significantly increased in CSF. Although serum levels of beta 2-M
      were similar in the three groups, the CSF/serum ratios were higher in SSPE versus
      the MS group and in the MS versus the OND group. Levels of sIL-2R and sCD8 were
      higher in SSPE CSF than OND CSF; however, there were no differences between
      levels in SSPE and MS CSF. The levels of sIL-2R were increased in SSPE sera
      compared to those of MS or the OND group, whereas levels of sCD8 in serum from
      the three groups were similar. The findings of increased CSF/serum ratio of beta
      2-M and higher levels of serum sIL-2R and CSF sCD8 in SSPE patients are
      consistent with those seen in patients with acute and chronic viral infections.
      When the levels between the initial and follow-up CSF and serum samples from SSPE
      patients were compared, the data showed that CSF levels of sCD8 elevated during
      periods of clinical worsening and decreased during clinical improvement. In
      contrast, serum beta 2-M decreased during periods of worsening and increased
      during improvement. The measurement of serum beta 2-M and CSF sCD8 may be useful
      in SSPE patients as markers to monitor disease activity.

PMID- 1382910
TI  - Lupus-like autoimmune disease induced by interferon therapy for
      myeloproliferative disorders.
AB  - Symptoms of autoimmune disease were evaluated in 125 patients with chronic
      myelogenous leukemia (CML) and in 12 patients with essential thrombocythemia
      undergoing treatment with recombinant interferon (IFN)-alpha-2b plus/minus low
      dose recombinant IFN-gamma. Twenty-seven of 137 patients (20%) developed
      rheumatoid symptoms. Furthermore, the incidence of antinuclear antibody (ANA)
      formation was studied. Elevated ANA titers were found in 5/19 (26%) of CML
      patients at the time of diagnosis and in 3/18 (17%) of patients treated with
      hydroxyurea or busulfan. During IFN treatment, 18 of 25 tested patients (72%) had
      elevated ANA titers. In 15 of these ANA-positive patients, clinical signs of
      autoimmune disease appeared. All these patients were under long-term IFN
      treatment and were in remission of disease. In three patients criteria for
      systemic lupus erythematosus were fulfilled. Severity of side effects had led to
      the discontinuation of IFN treatment in these patients. The data indicate that
      IFN-alpha and IFN-gamma can induce ANA associated with autoimmune disease in
      patients with myeloproliferative disorders.

PMID- 1382911
TI  - Predominant usage of V beta 8.3 T cell receptor in a T cell line that induces
      experimental autoimmune uveoretinitis (EAU).
AB  - Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune
      disease induced in animals by immunization with retinal proteins (or synthetic
      fragments derived from them) in adjuvant, and it is considered a model of human
      autoimmune diseases of the eye. To study the T cell clonotypes that may be
      involved in EAU, we analyzed the T cell repertoire of three related T cell lines:
      the pathogenic line LR16, specific to the major uveitogenic epitope of IRBP; its
      pathogenic subline J; and its nonpathogenic subline A. We examined the expression
      of the genes coding for the variable regions of the 20 known Lewis rat T cell
      antigen receptor (TCR) V beta families. The nonpathogenic subline was found to
      contain mostly T cells expressing V beta 5, V beta 8.2, and V beta 19 while the
      pathogenic subline consisted mainly of cells expressing V beta 8.3 TCRs. Genomic
      Southern blot analysis of DNA from the pathogenic subline showed that V beta 8.3
      expressing T cells were the dominant clonotype, and DNA sequence analyses of V
      beta 8.3 cDNAs revealed that two V beta 8.3 TCRs were expressed in the pathogenic
      subline. One of the V beta 8.3 cDNAs encoded a variable region gene segment
      identical to previously reported rat V beta 8.3 TCR while the other differed by
      two amino acids in the second complementarity determining region (CDR2). Taken
      together with previous data showing overrepresentation of V beta 8-expression in
      T cell lines that induce EAU, but not in nonuveitogenic T cell lines, our results
      suggest that V beta 8.3-expressing T cells represent a pathogenic clonotype in
      IRBP-induced EAU.

PMID- 1382912
TI  - Iatrogenic acute spinal epidural abscess with septic meningitis: MR findings.
AB  - A contaminated catheter used in epidural anesthesia in a 71-year-old female
      produced acute epidural abscess and septic meningitis. Methicillin-resistant
      Staphylococcus aureus (MRSA) was detected in a culture of the epidural pus. Both
      T1- and T2-weighted MR images showed low intensity mass lesion compressing the
      thecal sac behind the vertebral body L3. The low intensity lesion was probably
      pus with gas component. In these low intensity lesions in MR findings with gas
      component, MR was superior to myelography because it visualized both the degree
      of compression to the thecal sac and extension of the lesion in all directions.

PMID- 1382913
TI  - Pancreatic secretion of lysosomal enzymes stimulated by intraduodenal
      instillation of a liquid meal in rabbits.
AB  - 1. Studies have been performed to determine the effect of intraduodenal food on
      pancreatic secretion of lysosomal enzymes. 2. Intraduodenal instillation of a
      liquid meal (3 g/kg body weight; 15.3% protein, 19.7% fat, 59.7% carbohydrate)
      caused significant increases in pancreatic juice volume and pancreatic secretion
      of amylase and protein compared with basal values for 2h after instillation in
      anaesthetized rabbits. 3. Intraduodenal instillation of a liquid meal also caused
      significant increases in pancreatic secretion of three lysosomal enzymes
      (cathepsin B, N-beta-acetyl-galactosaminidase and N-acetyl-beta-glucosaminidase)
      compared with basal values for 2h after instillation. 4. In addition, there were
      significant correlations between cathepsin B secretion and amylase secretion (r =
      0.7764, P < 0.001) and between cathepsin B secretion and protein secretion (r =
      0.6216, P < 0.001), both in basal conditions and in response to the liquid meal.
      5. These results are evidence for the localization of lysosomal enzymes in the
      secretory granules-zymogen granules in normal acinar cells, and also indicate
      that the pancreatic secretion of lysosomal enzymes is gut-hormone-regulated.

PMID- 1382914
TI  - A new method to measure renal tubular degradation of small filtered proteins in
      man using radiolabelled aprotinin (Trasylol).
AB  - 1. A method has been developed to measure the renal tubular degradation of small
      filtered proteins in man using radiolabelled aprotinin (Trasylol), a 6500 Da
      cationic polypeptide. 2. Aprotinin (0.5 or 5.0 mg) was labelled with either 99mTc
      (40 MBq) or 131I (1 MBq) and injected intravenously in 19 renal patients (10 with
      normal renal function and nine on haemodialysis). Activity in plasma and urine
      was measured over 48 h, and chromatography with Sephadex-G-25-M was used to
      separate labelled aprotinin from free 99mTcO4- or 131I-. Renal uptake was
      measured for 99mTc-labelled aprotinin only. 3. The volumes of distribution were
      similar in all patients: 18.2 +/- 0.4 litres in those with normal renal function
      and 20.2 +/- 0.1 litres in the others. Chromatography showed all plasma activity
      as undegraded aprotinin and urine activity only as the free labels (99mTcO4- or
      131I-). 4. In patients with normal renal function, activity in the kidneys rose
      rapidly to 24.2 +/- 2.8% of dose after 90 min and to 42.2 +/- 3.4% of dose after
      24 h. In the dialysis patients, activity over the kidneys was only 2.7 +/- 0.8%
      of dose at 24 h. Extra-renal uptake was insignificant in all patients with normal
      kidney function. 5. Both 99mTcO4- and 131I- appeared in the urine promptly after
      injection, and the rates of excretion of the two isotopes were similar, varying
      little over 24 h (1.8 +/- 0.04% of dose/h and 1.7 +/- 0.04% of dose/h for 99mTc
      and 131I, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382916
TI  - Proteinase inhibitory activity in the plasma of a mollusc: evidence for the
      presence of alpha-macroglobulin in Biomphalaria glabrata.
AB  - 1. A methylamine-sensitive inhibitor was present in the plasma of B. glabrata. 2.
      This inhibitor decreased trypsin activity against a protein substrate, however
      trypsin retained activity against a low molecular weight substrate in the
      presence of the inhibitor. 3. Snail plasma protected trypsin from inhibition by
      soybean trypsin inhibitor. 4. The results give evidence for an alpha
      macroglobulin proteinase inhibitor in the plasma of this gastropod mollusc.

PMID- 1382915
TI  - Effects of lysine infusion on the renal metabolism of aprotinin (Trasylol) in
      man.
AB  - 1. Aprotinin (Trasylol) is a cationic 6500 Da polypeptide that inhibits
      proteolytic enzymes, and when labelled with 99mTc it is a reproducible marker for
      the renal tubular turnover of small filtered proteins in man. Lysine potently
      inhibits tubular peptide uptake, and may thus depress the uptake and metabolism
      of aprotinin. This was investigated in 14 glomerulonephritic patients with normal
      renal function and variable proteinuria and in one healthy subject. 2. 99mTc
      labelled aprotinin was given intravenously alone, and again 3 days later,
      immediately after the intravenous administration of 3-6 g of lysine, followed by
      an infusion over 1 h of 0.3-1.9 g of lysine/kg in individual patients. Activity
      over kidneys and in urine was measured over 24 h and chromatography was used to
      separate the undegraded peptide from free isotope. 3. At the low dosage of lysine
      (< 0.8 g/kg) given to six patients, kidney activity (representing tubular uptake)
      was unchanged, but early urine samples contained some undegraded aprotinin.
      Urinary excretion of free isotope, representing tubular metabolism, fell from 1.6
      +/- 0.2% of dose/h with no lysine to 0.9 +/- 0.1% of dose/h in the 24 h after
      lysine, suggesting suppression of tubular aprotinin degradation. Corrected
      fractional degradation was calculated from the mean urinary excretion of free
      isotope over a given interval, determined by chromatography, divided by the mean
      cumulative kidney counts over this same interval, and this also fell after lysine
      from 0.06 +/- 0.006 to 0.03 +/- 0.006 h-1 (P < 0.005) between 3.75 and 24
      h.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1382917
TI  - D-glyceraldehyde-3-phosphate dehydrogenase from HeLa cells--2. Immunological
      characterization.
AB  - 1. An immunological relationship between GPDH from HeLa cells and those from
      other phylogenetically different sources was carried out. 2. It was found that
      HeLa cell anti-GPDH antibody presented an immunological cross-reaction
      specificity with GPDH from HeLa cells, Caiman sp. muscle and human mammary tumor
      tissue and a partial one with GPDH from Anas sp. muscle.

PMID- 1382918
TI  - Adequacy of language function and verbal memory performance in unilateral
      temporal lobe epilepsy.
AB  - We examined adequacy of language functions, their influence on verbal learning
      and memory performance, and the relative effects of language function and
      laterality of seizure focus on the memory performance of 99 left-hemisphere
      dominant patients with invasively verified epilepsy of left (N = 47) or right (N
      = 52) temporal lobe origin. Patients with left temporal lobe epilepsy (TLE)
      scored significantly lower than the right TLE group on several aphasia battery
      subtests (Visual Naming, Sentence Repetition, Token Test, Reading Comprehension,
      Aural Comprehension). Adequacy of language function (nominal speech) was
      significantly related to verbal learning and memory performance for both left and
      right TLE groups. Finally, comparison of the predictive significance of
      laterality of TLE and adequacy of language function indicated that language
      functions (Visual Naming and Aural Comprehension), but not laterality of TLE,
      were significant predictors for verbal learning and memory performance. It is
      concluded that: 1) adequacy of basic language functions is particularly
      compromised in left TLE, 2) there is a significant relationship between adequacy
      of language function and several aspects of verbal learning and memory ability in
      both left and right temporal lobe groups, and 3) clinical assessment and
      theoretical models of memory need to consider these relationships.

PMID- 1382920
TI  - Visuospatial judgment and right hemisphere disease.
AB  - The performances of patients with stroke-produced unilateral hemispheric lesions
      on a test requiring the identification of lines were examined in the light of a
      recent report that contradicted previous observations. The study confirmed the
      results of earlier studies that patients with lesions of the right hemisphere
      show a remarkably high frequency of defective performances while those with
      lesions of the left hemisphere do not. Possible reasons for findings that deviate
      from this rule are discussed.

PMID- 1382919
TI  - Tactile agnosia and tactile aphasia: symptomatological and anatomical
      differences.
AB  - Two patients with tactile naming disorders are reported. Case 1 (right hand
      tactile agnosia due to bilateral cerebral infarction) differentiated tactile
      qualities of objects normally, but could neither name nor categorize the objects.
      Case 2 (bilateral tactile aphasia after operation of an epidural left parietal
      haematoma) had as severe a tactile naming disturbance as Case 1, but could
      categorize objects normally, demonstrating that tactile recognition was
      preserved. Case 1 may be the first case of tactile agnosia clearly differentiated
      from tactile aphasia. CT scans of Case 1 revealed lesions in the left angular
      gyrus, and in the right parietal, temporal, and occipital lobes. Case 2 had
      lesions in the left angular gyrus and of posterior callosal radiations. Our
      findings suggest that tactile agnosia appears when the somatosensory association
      cortex is disconnected by a subcortical lesion of the angular gyrus from the
      semantic memory store located in the inferior temporal lobe, while tactile
      aphasia represents a tactual-verbal disconnection.

PMID- 1382921
TI  - Hematopoietic growth factors: current knowledge, future prospects.
AB  - The introduction of hematopoietic growth factors into clinical medicine
      represents one of the more exciting developments in oncology in the past several
      years. The identification, gene cloning, and large-scale production of
      hematopoietic growth factors represent important examples of the practical
      benefits that may accrue from application of the sophisticated technology derived
      from recombinant DNA research. Research, both at the bench and by the bedside,
      has proceeded at an extraordinarily rapid pace in this field over the past five
      years, leading to an abundance of new information, novel promising agents, and
      important clinical controversies related to the biology and appropriate clinical
      applications of hematopoietic growth factors. With these agents, for the first
      time in history, the production of human blood cells can be systematically
      manipulated in vivo in an effort to optimize physiology beyond the endogenous
      host response. Additionally, investigators utilizing purified hematopoietic
      growth factors as reagents may provide crucial insights into the mechanisms of
      blood cell production in health and in various disease states. This review aims
      to summarize the current state of knowledge regarding the control of blood cell
      production by specific factors and to put these data in the context of clinical
      medicine. The emphasis will be on factors that primarily influence myeloid
      (rather than lymphoid) cell growth, differentiation, and activation, and the
      clinical focus will be on applications in oncologic therapeutics and in the
      treatment of primary hematologic disorders. By reviewing what we know and what
      has already been done, we may be better able to define the important questions
      that remain and to formulate the means to answer our current uncertainties about
      the activities and clinical uses of hematopoietic growth factors.

PMID- 1382922
TI  - [Squamous cell cancer of the esophagus. Treatment concept at the surgical clinic
      of the Munich Technical University].

PMID- 1382923
TI  - [Results of treatment in esophageal cancer].
AB  - 204 patients were treated for esophageal cancer from 1.1.1986 until 1.6.1992
      (carcinoma of the hypopharynx: n = 12, adenocarcinoma of the endobrachyesophagus:
      n = 82, primary esophageal cancer: n = 110). Out of the primary esophageal
      cancers 84 tumors (76%) were resected and 24% had palliative endoscopic and/or
      irradiation therapy. The stage distribution of the resected patients was: stage
      I: 7.1%, stage IIa: 35.7%, stage IIb: 11.9%, stage III: 33.3%, stage IV: 11.9%.
      The total morbidity of the resected patients amounted to 32.1%, the 30 days
      mortality to 7.1%, and the in hospital mortality to 9%. These data show no
      significant difference to the results of palliative endoscopic procedures
      (morbidity: 42.3%, mortality: 7.7%). None of the conservatively treated patients
      survived longer than 12 months whereas resected individuals had a 5-year-survival
      rate of 20%. The most predictive factors for prognosis were: Depth of tumor
      invasion (p less than 0.01), R-classification (p less than 0.05), and the
      lymphonodular status (p less than 0.05). A perioperative irradiation was
      effective in T3- and T4-tumors.

PMID- 1382924
TI  - [Surgery of esophageal cancer].
AB  - From 1975 through 1988, 257 patients with carcinoma of the thoracic oesophagus
      have been treated in our department. Operability was 90% (232/257), overall
      resectability 77% (198/257) and for the operated group 85% (198/232). Hospital
      mortality was 9.6% but decreased to 3% over the period 1986-1988. There were 65%
      squamous cell epitheliomas and 35% adenocarcinomas. pTNM staging was as follows:
      Stage I: 11.6%, Stage II: 23.2%; Stage III: 37.9%; Stage IV: 27.3%. Overall
      survival was 62.5% after one year, 42.4% after 2 years and 30% after 5 years.
      According to the pTNM staging 5-year survival was 90% for stage I, 56% for stage
      II, 15.3% for stage III. There was no 5-year survival for patients with stage IV
      carcinoma. There were statistically significant differences according to tumour
      localisation, pathologic type, sex and age. Introducing extensive resection and
      extended lymphadenectomy seems to improve significantly survival in patients in
      whom an operation with curative intention was performed. The 1-year survival was
      90.8 versus 72%, 2-year survival was 81 versus 46% and 5-year survival was 48.5
      versus 41% for respectively radical and non-radical resections. Radical surgery
      in stage IV carcinoma substantially prolonged median survival from 6 months to 1
      year. From this study it can be concluded that in experienced hands, surgery
      today offers the best chances for optimal staging, potential cure and prolonged
      high-quality palliation.

PMID- 1382926
TI  - [Hyperamylasemia in acute exacerbation of patients with chronic respiratory
      failure].
AB  - Serum amylase level was determined in 129 cases (225 episodes) of chronic
      respiratory failure at acute exacerbation and in 59 cases (62 episodes) of
      pneumonia without respiratory failure as control. Cases with accompanying
      diseases, such as acute pancreatitis, parotiditis, ileus and renal dysfunction,
      which were expected to develop hyperamylasemia were excluded. The 225 episodes
      were divided according to the causes of acute exacerbation into 4 groups:
      pneumonia, bronchitis, right heart failure without infection, and others (e. g.
      hemoptysis). Hyperamylasemia (greater than 400 S-U) was observed in groups of
      pneumonia (15/40 = 35.5%) and bronchitis (12/95 = 12.6%), respectively but not in
      those of right heart failure without infection (0/73 = 0%) and other causes (0/17
      = 0%). As a result, hyperamylasemia was found only under conditions of
      inflammation of lung parenchyma and bronchi with acute exacerbation of
      respiratory failure. On the other hand no hyperamylasemia was observed in 62
      episodes of pneumonia alone without respiratory failure. It was concluded that
      both respiratory tract infection and acute respiratory failure are necessary
      factors for development of hyperamylasemia originating from lung or bronchi.

PMID- 1382925
TI  - [Detection of cancer cells in peritoneal fluid or washing by immunocytochemical
      staining with monoclonal antibodies].
AB  - Three Monoclonal Antibodies (McAbs) against ovarian carcinoma and anti-CEA McAb
      were used for peroxidase-antiperoxidase (PAP) staining to detect cancer cells
      from 42 cases of either pleural fluid or ascites and peritoneal washings of
      cancer patients with ovarian cancer and endometrial carcinoma. The results showed
      that the positive rates by PAP staining of every group were higher than that by
      ordinary papanicolaou staining, especially in the group of epithelial ovarian
      carcinoma with primary surgery. There were significant differences by these two
      methods (P less than 0.05). It is concluded that a suitably chosen a panel of
      McAbs can be used in identifying differential diagnosis in ovarian cancer and the
      combined use of two methods will give more help to clinics.

PMID- 1382927
TI  - [A prospective trial of hemodilution therapy in acute cerebral infarction].
AB  - Ninety two 50-year-old-or-more patients with acute (less than 72 hours) cerebral
      infarction involved middle cerebral artery region and hematocrit of 40% or more
      were prospectively randomised to either hemodilution group (by rapid venesection,
      venous infusion of autologous plasma and 500 ml dextran 40) or standard therapy
      group. Effects of hemodilution on acute cerebral infarction were evaluated by
      clinically neurological deficit scores, hemorheological parameters and size of
      infarction. The results of our clinical trial are: 1. Clinical efficacy of
      hemodiluted patients is significantly superior to that of standard treatment
      patients. Effective rates are 63.04% and 41.30% respectively (P less than 0.05).
      2. At 48th hour after hemodilution there are profound decreases in hematocrit,
      blood viscosity at high shear rate and blood viscosity at low shear rate. These
      changes last more than four weeks. Whereas in standard group, hemorheological
      parameters do not evidently change. 3. Sizes of cerebral infarction do not
      distinctly change in both groups between at entry and at the fourth weekend after
      treatment.

PMID- 1382929
TI  - [The content of the DNA, the RNA and the wet weight and the RNA:DNA and the wet
      weight:DNA ratio in different tissues during the growth of chickens. 2. Analysis
      of the kidney, the spleen, the gizzard and the M. pectoralis superficialis].
AB  - At chicken of the race "White Leghorn" the content of nuclei in the kidney was
      highest (14.60 x 10(9)) on the 203rd, in the spleen on the 112th (14.85 x 10(9)),
      in the gizzard on the 112th (18,24 x 10(9)) and in the M. pectoralis
      superficialis on the 168th day (36.42 x 10(9)) after hatching. The biggest fresh
      weight:DNA-ratio was determined in the kidney on the 203rd (285), in the spleen
      on the 28th (92) and in the gizzard (694) and in the M. pectoralis superficialis
      (1984) on the 203rd day. The DNA-concentration on the 2nd day after hatching in
      the kidney was 4,56 +/- 0,36, in the spleen 11.49 +/- 0.84, in the gizzard 1.85
      +/- 0.13 and in the M. pectoralis superficialis 2.96 +/- 0.18 mg/g wet weight
      respectively the RNA:DNA-ratio in these tissues 1.00, 0.88, 1.70 and 0.85. The
      growth of tissues by the increase of the number of cells (hyperplasia) and of the
      volume of cells (hypertrophy) is described.

PMID- 1382928
TI  - Evaluation of three hepatitis C virus-related antibodies C100, KCL-163, JCC.
      Tests for screening blood donors.
AB  - To evaluate the most effective method for detecting hepatitis C virus (HCV)
      carriers in a large population of blood donors, HCV-related antibodies were
      measured in 919 donor serum samples using three different enzyme-linked
      immunosorbent assays. The antibodies were C100 and KCL-163, nonstructural
      proteins of HCV, as well as JCC, a translation product of the presumptive HCV
      core gene. Fourteen (1.5%), 12 (1.3%), and 13 (1.4%) specimens were positive for
      anti-C100, anti-KCL-163, and anti-JCC, respectively. HCV RNA was detected by the
      polymerase chain reaction in seven (25.0%) of the 28 specimens that were anti-HCV
      positive by at least one of the three assays. Four of the seven specimens were
      detected by anti-C100 screening, while the remaining three were not. All seven
      specimens were positive for KCL-163 and/or JCC antibodies. These findings suggest
      that screening for both KCL-163 and JCC antibodies may be of particular use in
      accurately identifying HCV-positive blood.

PMID- 1382930
TI  - The NMDA receptor, NMDA antagonists and epilepsy therapy. A status report.

PMID- 1382931
TI  - Thrombolytic therapy for acute myocardial infarction. A review .
AB  - In the past 10 years, thrombolytics have become standard therapy for acute
      myocardial infarction. Although the ability of streptokinase to lyse clot was
      first recognised in the 1930s, thrombolytic therapy was not used to treat acute
      myocardial infarction until the early 1980s, when the importance of thrombosis in
      the pathogenesis of acute infarction was fully recognised. In addition to
      streptokinase and urokinase, recombinant human tissue plasminogen activator (tPA)
      and anistreplase were developed and widely used in the 1980s. Saruplase
      (prourokinase) and BM-06022 (recombinant plasminogen activator) have also
      undergone human clinical studies. All of these agents are effective at achieving
      clot lysis and coronary patency. Large, randomised clinical trials have
      demonstrated that thrombolytic therapy reduces mortality in patients with ST
      elevation treated within the first 6 to 12 hours of acute infarction, with an
      approximately 0.5% risk of intracranial haemorrhage. Recent data have more
      clearly identified which patients benefit from thrombolytic therapy. Efforts have
      been made to improve the speed of reperfusion, decrease reocclusion, simplify
      administration and reduce adverse effects. The characteristics of fibrin
      specificity and more rapid clot lysis with tissue plasminogen activator have not
      yet been translated into overall clinical benefit compared with the less
      expensive streptokinase. The lack of close association of improved early patency
      and improved global left ventricular function with improved survival challenges
      the very paradigm which led to the use of thrombolytic therapy for acute
      myocardial infarction. The need for development of additional methods for
      evaluation of new thrombolytic agents is evident.

PMID- 1382932
TI  - New uses of anticonvulsant drugs in psychosis.
AB  - Psychotic patients not adequately relieved by neuroleptic drugs often improve
      when anticonvulsants are added. In bipolar disorders and organic psychoses,
      anticonvulsants can sometimes be used to replace neuroleptics. No individual
      anticonvulsant is clearly, consistently superior. Patients who fail on one agent
      may improve on the next. Clonazepam is an excellent adjunct to neuroleptic
      therapy, but there is little evidence that it is effective as monotherapy.
      However, it is safe, sedates rapidly, and has an excellent patient tolerability
      profile. Carbamazepine is the best established drug for patients with bipolar
      disorders, particularly for rapid cyclers, and is often effective monotherapy.
      The therapeutic profile of valproic acid (sodium valproate) is similar to that of
      carbamazepine, but its side effects are quite different and are often preferred.
      Other anticonvulsants are little studied, but might be chosen to avoid certain
      side effects, or after better-studied drugs have failed. The pharmacological
      basis behind using anticonvulsants in psychoses is primarily empirical. In almost
      every case it has been clinicians who have first noted the beneficial effects of
      these drugs. Theories such as that of Post have followed.

PMID- 1382933
TI  - Noninvasive and invasive strategies for the prevention of sudden death after
      myocardial infarction. Value, limitations and implications for therapy.
AB  - Each approach to the prevention of sudden death after myocardial infarction
      should be analysed not only according to its value in the risk stratification of
      patients but also for its potential impact in guiding therapy. With the results
      of 2 or more noninvasive tests [assessment of left ventricular ejection fraction
      (LVEF) by radionuclide ventriculography, grade of ventricular arrhythmias and
      heart rate variability by Holter monitoring, and ventricular activation by signal
      averaged electrocardiography], most patients may be stratified into 'very high'
      and 'very low' risk groups. For patients with 2 or more abnormal noninvasive
      tests, electrophysiological studies (EPS) may be recommended: if sustained
      ventricular tachycardia (VT) is not induced, patients may be reassured and left
      without antiarrhythmic therapy other than beta-blockers. For patients with low
      LVEF, treatment with beta-blockers may be recommended based on post hoc analysis
      of large prospective trials, while some of the randomised studies with
      angiotensin converting enzyme (ACE) inhibitors suggest that these agents may also
      reduce the risk of sudden death. For patients with high grade ventricular
      arrhythmias, beta-blockers and amiodarone may be recommended: the first, based on
      post hoc analysis of the Beta Heart Attack Trial, while data supporting the use
      of amiodarone come from prospective, yet small randomised studies. Empirical or
      Holter-guided therapy with class 1 antiarrhythmic drugs have not been found
      useful and may indeed be detrimental. For patients with inducible sustained VT,
      treatment should be guided by repeated EPS, as empirical antiarrhythmic therapy
      has not been found useful. However, the value of EPS-guided therapy remains to be
      proven. Patients with inducible sustained VT refractory to antiarrhythmic drugs
      are at very high risk. Implantation of an automatic defibrillator is an
      attractive option for these patients, to be confirmed by ongoing trials.

PMID- 1382935
TI  - Brain tumours in infants. Preferred treatment options.
AB  - Since the advent of CT scan and MRI, the diagnosis of neonatal infantile brain
      tumours and related diseases is more easily accomplished; their rarity is
      reflected in the small number of cases reported. Astrocytomas and teratomas are
      the most common oncotypes in infants and particularly in neonates. Surgical
      mortality rates are not high and have decreased because of the advances of
      diagnosis and improvements in treatment. However, the survival rates are
      disappointing. Follow-up shows little improvement in last 2 decades. Adjuvant
      therapy is still a problem; radiotherapy gives a small percentage of favourable
      later neuropsychological results. Postoperative chemotherapy added to maximal
      surgical resection and delayed irradiation may prolong survival with only minimal
      short term neurotoxicity in very young children with malignant tumours. Different
      protocols of chemotherapy are suggested but still not definitely accepted.
      Radical surgery seems to have a higher chance of success in neonates than infants
      and remains the less aggressive means; in low grade gliomas after total removal
      it may be preferable to perform a second operation if the tumour recurs and
      withhold irradiation and chemotherapy until after 3 years of age.

PMID- 1382934
TI  - Diagnosis and drug treatment of acute pyelonephritis.
AB  - The term pyelonephritis, which denotes infection of the renal pelvis and of the
      renal tissue, covers a spectrum of entities, the gravity and hence treatment of
      which depend upon the organism, its sensitivity to antibiotics, the presence or
      absence of urinary tract obstruction, and the host's background. The common form
      affects young females, is due to uropathogenic but multisensitive strains of
      Escherichia coli, and is easily treated by a 10- to 20-day course of
      antibiotic(s). In males, children and immunocompromised patients, renal and
      urinary tract imaging is necessary to determine the cause of the infection, the
      severity of the lesions and thus to guide the duration of treatment, which
      comprises antibiotic combinations for several weeks. Pyelonephritis during
      pregnancy may be serious, and treatment is restricted to certain antibiotics.
      Aminoglycosides, amino- or carboxypenicillins (alone or associated with
      clavulanic acid), ureidopenicillins (e.g. mezlocillin, piperacillin),
      fluoroquinolones (e.g. ciprofloxacin, ofloxacin, pefloxacin), cephalosporins,
      monobactams (e.g. aztreonam), carbapenems (e.g. imipenem) and the combination of
      trimethoprim plus a sulphonamide [e.g. cotrimoxazole
      (trimethoprim/sulfamethoxazole)] offer a wide choice of bactericidal agents which
      may be used for the treatment of pyelonephritis. However, the selection among
      them also depends on availability, antimicrobial spectrum, tolerance and cost.

PMID- 1382936
TI  - Budesonide. An updated review of its pharmacological properties, and therapeutic
      efficacy in asthma and rhinitis.
AB  - Inhaled budesonide is now well established in the management of adult and
      childhood asthma, and when nebulised, shows considerable promise in recurrent
      wheezing and in severe asthma in infants. Studies conducted since the drug was
      previously reviewed in the Journal in 1984 have confirmed the comparable efficacy
      of equal doses of budesonide and beclomethasone dipropionate, the ability of
      budesonide to reduce oral maintenance corticosteroid requirements, and
      demonstrated its potential as first-line treatment of mild to moderate asthma.
      Recent studies have established the usefulness and good tolerability of
      intranasal budesonide in the treatment of seasonal allergic and perennial
      rhinitis where the drug is more effective than disodium cromoglycate and at least
      as effective as beclomethasone dipropionate. After up to 10 years of treatment
      with inhaled budesonide there is no evidence that the drug damages the
      tracheobronchial lining or the nasal mucosa. Inhaled corticosteroids continue to
      play an important role in the treatment of asthma with an increasing focus on
      their role as first-line therapy, and widespread clinical experience has shown
      budesonide is an effective and well tolerated member of this class which should
      be considered where inhaled or intranasal administration of a corticosteroid is
      indicated.

PMID- 1382937
TI  - Imipenem/cilastatin. A reappraisal of its antibacterial activity, pharmacokinetic
      properties and therapeutic efficacy.
AB  - Imipenem is an antibacterial agent of the carbapenem class of beta-lactams, with
      a very broad spectrum of activity that includes most Gram-negative and Gram
      positive pathogens, aerobes and anaerobes, and with marked activity against
      species producing beta-lactamases. It is coadministered with cilastatin, a renal
      dehydropeptidase inhibitor that prevents renal metabolism of imipenem. As initial
      monotherapy, imipenem/cilastatin provides effective and well-tolerated treatment
      of moderate to severe infections in various body systems, including intra
      abdominal, obstetric and gynaecological, lower respiratory tract, skin and soft
      tissue, and urinary tract infections, and also in bacteraemia and septicaemia,
      and in patients with malignancy-related febrile neutropenia. It is likely to be
      of particular benefit in cases where bacterial pathogens have not yet been
      identified, such as in the treatment of serious infections in immunocompromised
      patients, or in an intensive care setting. Thus, imipenem/cilastatin is effective
      as initial monotherapy of a variety of infections, including infections in
      neutropenic patients, with a clear role in empirical treatment of mixed
      infection.

PMID- 1382938
TI  - Indobufen. A review of its pharmacodynamic and pharmacokinetic properties, and
      therapeutic efficacy in cerebral, peripheral and coronary vascular disease.
AB  - Indobufen is an inhibitor of platelet aggregation which acts by reversibly
      inhibiting the platelet cyclo-oxygenase enzyme. Improvements in walking distances
      and microcirculatory parameters have been achieved during therapy with indobufen
      in patients with peripheral vascular disease and intermittent claudication.
      Indobufen has been shown to be as effective as aspirin plus dipyridamole in
      preventing the reocclusion of coronary and femoro-popliteal artery bypass grafts
      and has been shown to significantly reduce platelet deposition on haemodialysis
      membranes. Initial studies have also indicated that indobufen may have a
      prophylactic effect on the incidence of secondary thrombotic events following
      transient ischaemic attack or mild stroke and may be effective in the prophylaxis
      of migraine. Indobufen is well tolerated following oral administration and has
      been associated with a low incidence of adverse effects rarely requiring
      withdrawal of treatment. Thus, available evidence indicates that indobufen may be
      an effective alternative to aspirin for the treatment of cerebral, peripheral and
      coronary vascular diseases with the advantage of a lower incidence of
      gastrointestinal effects compared to high dose aspirin, rendering indobufen more
      suitable for longer term therapy.

PMID- 1382939
TI  - Enoxaparin. A review of its pharmacology and clinical applications in the
      prevention and treatment of thromboembolic disorders.
AB  - Enoxaparin (PK 10169) belongs to the group of low molecular weight heparins which
      have a greater bioavailability and longer half-life than unfractionated heparin,
      permitting less frequent subcutaneous administration. In well controlled trials
      in surgical patients at high risk of deep venous thrombosis (DVT), enoxaparin has
      demonstrated prophylactic efficacy against venographically confirmed DVT at least
      equal to that observed with unfractionated heparin. Efficacy has also been
      demonstrated in patients at moderate risk and in limited investigations using
      125I-fibrinogen scanning in nonsurgical patients at risk of DVT; in addition,
      enoxaparin appears to provide effective treatment of established DVT. In clinical
      studies, enoxaparin has also prevented coagulation of extracorporeal circulation,
      maintaining the patency of the circuit in patients undergoing haemodialysis.
      Thus, enoxaparin represents an effective alternative in the prophylaxis and
      treatment of thrombosis, with the convenience of less frequent administration
      than unfractionated heparin and the possible advantage of a lesser propensity for
      bleeding complications.

PMID- 1382940
TI  - Transdermal Nicotine. A review of its pharmacodynamic and pharmacokinetic
      properties, and therapeutic efficacy as an aid to smoking cessation.
AB  - Transdermal nicotine delivery systems are a cigarette smoking cessation aid
      designed to deliver nicotine into the systemic circulation via the skin. The
      partial replacement of plasma nicotine, which would have otherwise been obtained
      from cigarettes, reduces the severity of nicotine withdrawal symptoms, and so
      allows the smoker to abstain from smoking more easily. The systems are available
      in 16- and 24-hour application regimens, and are recommended for daily use for up
      to 20 weeks, including a series of 'weaning-off' courses. Clinical trials have
      shown that abstinence rates of 30 to 41% can be achieved during the first 6 weeks
      of application of transdermal nicotine systems, compared with 4 to 21% with
      placebo systems. The use of concomitant behavioural therapy may increase the
      success of treatment, with initial abstinence rates of up to 86% reported.
      However, long term abstinence rates (greater than 6 months) are considerably
      lower with or without behavioural therapy, often falling to less than half of the
      initial rates. Transdermal nicotine systems have been well tolerated in clinical
      trials, with local irritation at the site of application being the most common
      adverse event. Mild gastric, central nervous system (CNS) and sleep disturbances
      have also been reported. The ease of use and unobtrusive nature of the systems
      have resulted in a high degree of patient compliance. Thus, transdermal nicotine
      systems offer a convenient form of nicotine replacement therapy which are well
      tolerated and, due to their pharmacokinetic profile, probably have a low
      dependency potential. The short term abstinence rates achieved with this therapy
      are encouraging; however, the maintenance of abstinence in the long term is
      harder to achieve. Transdermal nicotine replacement therapy, therefore,
      represents an important advance in the difficult area of smoking cessation
      management.

PMID- 1382941
TI  - Stage specific, (O4+GalC-) isolated oligodendrocyte progenitors produce MBP+
      myelin in vivo.
AB  - O4+/A007+GalC- proligodendroblasts represent a distinct stage of development in
      the oligodendrocyte lineage, occurring just prior to the appearance of
      postmitotic GalC+ oligodendrocytes. These cells, isolated directly from postnatal
      rat telencephalon by an immunopanning procedure, can terminally differentiate and
      myelinate axons when transplanted back into an in vivo environment. Specifically,
      after 30 days in the brain of newborn shiverer mouse hosts, O4+GalC-
      oligodendrocyte progenitors produced myelin basic protein positive (MBP+)
      patches. These MBP+ patches, examined by both light and confocal microscopy,
      contained oligodendrocyte cell bodies and ensheathed host shiverer axons
      morphologically similar to those found in normal rat brain at an analogous age.
      These results suggest that isolated O4+GalC- cells can become biochemically
      mature oligodendrocytes with the capacity to elaborate myelin sheaths, and
      further define the period of development during which oligodendrocytes retain
      their capacity to myelinate axons when given a receptive environment.

PMID- 1382942
TI  - Transvesical prostatectomy in Tikur Anbessa Hospital, Addis Ababa.
AB  - This is a retrospective study of a hundred and thirty patients with benign
      prostatic hypertrophy (BPH) treated at the Tikur Anbessa Hospital with suprapubic
      transvesical prostatectomy (STVP) from September 1984 to August 1988. The
      commonest presenting complaints were frequency of micturition noted in 113 (87%)
      patients and acute urinary retention in 102 (79%). The prostate was enlarged in
      all patients with an average weight of 70.0 gm in the 60 specimen weighed. Forty
      (31%) patients received two units of blood each. Sixty five (50%) developed
      immediate post operative complications and four patients died during the first
      post operative week giving a mortality rate of 3.0%. The duration of
      postoperative hospital stay was two to three weeks. It is concluded that
      transvesical prostatectomy is satisfactory modality of treatment for BPH in
      situations where facilities for transurethral prostatectomy (TUR) are not
      available as STVP can be accomplished with an acceptable morbidity and mortality.

PMID- 1382943
TI  - Feto-maternal interaction of IGF-I and its binding proteins in fetal growth.
AB  - Elevated levels of maternal IGF-I and IGF-binding proteins IGFBP-1 are regulated
      by placental hormones rather than pituitary control during pregnancy. Maternal
      IGF-I promotes fetal growth by stimulating nutrient transfer to fetus through
      placenta and IGFBP-1 suppresses fetal growth by inhibiting IGF-I binding to
      receptors in placenta. Since IGF-I and IGFBP-1 are produced in placenta and
      decidua, respectively, fetal growth is regulated by these substances in the
      locally formed paracrine system.

PMID- 1382944
TI  - Ictal EEG wave forms from epidural electrodes predictive of seizure control after
      temporal lobectomy.
AB  - Ictal wave form characteristics--frequency, spatial distribution, and duration-
      were analyzed for 140 complex partial seizures recorded from epidural strip
      electrodes implanted in 28 patients. None had abnormalities on imaging studies.
      All had bilateral electrode placements, unilateral seizure onsets, temporal
      lobectomies, and were followed for a mean of 33 months postoperatively. Sixteen
      patients (57%) became free of complex partial seizures: 12 had reductions in
      seizure frequency of at least 50% but were not seizure-free. The only predictor
      of the seizure-free state was the presence of low voltage fast activity (LVF), in
      the alpha or beta ranges, localized to one gyrus. This phenomenon occurred in
      14/16 seizure-free patients, 2/12 of others (P < 0.001). As seizures progressed,
      LVF typically increased in amplitude, propagated, and slowed into the theta
      range. Wave forms were classified into 8 categories based upon their frequency
      and morphology. Stepwise discriminant analysis of these wave forms, with
      consideration of whether they were localized or regional, revealed that both
      frequency and localization were critical for the post-surgical prognosis. The
      mere presence of a localized seizure onset was unreliable unless the wave form
      was taken into account. Well-localized rhythmic activity over 8 Hz at seizure
      onset from epidural subtemporal electrodes predicts surgical success. Slower
      rhythms imply greater separation in space and time from seizure onset.

PMID- 1382946
TI  - Negative brain potentials elicited by an unexpected color patch or word.
AB  - The purpose of this study was to examine whether a physical stimulus that
      deviates from a semantic context can elicit the N400 component of event-related
      brain potentials (ERPs). ERPs were recorded while 12 students judged the veracity
      of a simple statement (e.g., red/is not/blue) presented with the order of subject
      (S), object (O), and verb (V), which is normal in Japanese grammar. In one
      condition, S was a color patch and O was a word representing the color, while in
      the other condition, S was a color name and O was a patch. In both conditions, a
      late additional negative potential was elicited by the O stimulus when it was
      mismatched with S. In addition, the negativities elicited by the incongruous
      color patch and word had the same morphology and scalp distribution. The results
      indicate that not only a word but a physical stimulus which deviates from a
      semantic context can elicit the N400 component.

PMID- 1382945
TI  - Anterior brain electrical asymmetries in response to reward and punishment.
AB  - A variety of recent research indicates that when subjects are induced to
      experience certain negative emotions, there is greater suppression of alpha power
      in the right than left frontal region, while during the experience of positive
      emotion, alpha power asymmetry in this region shows the opposite pattern. We have
      conceptualized this asymmetry as reflecting specialization for approach and
      withdrawal processes in the left and right frontal regions, respectively. In this
      experiment, reward and punishment contingencies were directly manipulated to
      produce approach and withdrawal emotional states. In addition, subjects responded
      to imperative stimuli using either an approach response (finger press) or a
      withdrawal response (finger lift). EEG was recorded from multiple scalp
      locations. During the foreperiod prior to the response to the imperative stimuli,
      the EEG was extracted, Fourier-transformed and power computed in the theta, alpha
      and beta frequency bands. In addition, the contingent negative variation (CNV)
      was derived from the identical epoch. Reward trials were associated with greater
      left frontal alpha power suppression than punishment trials, while during the
      latter trials, there was greater right-sided frontal alpha power suppression than
      during reward trials. There was also some evidence to indicate that withdrawal
      responses were associated with greater right-sided alpha power suppression in the
      temporo-parietal region compared with approach responses. Power in the theta and
      beta bands did not systematically vary with condition. The CNV was larger during
      trials on which subjects responded quickly compared with slow trials, but did not
      differentiate between reward and punishment contingencies. The findings support
      the hypothesis that approach-related processes can be differentiated from
      withdrawal-related processes on the basis of asymmetrical shifts in alpha power
      in the frontal region. They also indicate that the CNV and spectral power
      estimates from the identical epochs reflect different neural processes.

PMID- 1382948
TI  - EEG activity during estral cycle in the rat.
AB  - EEG activity was recorded from right and left parietal cortex in adult female
      rats daily during 6 days. Immediately after EEG recording vaginal smears were
      taken and were microscopically analyzed to determine the estral stage. Absolute
      and relative powers and interhemispheric correlation of EEG activity were
      calculated and compared between estral stages. Interhemispheric correlation was
      significantly lower during diestrous as compared to proestrous and estrous.
      Absolute and relative powers did not show significant differences between estral
      stages. Absolute powers of alpha1, alpha2, beta1 and beta2 bands were
      significantly higher at the right parietal cortex. Comparisons of the same EEG
      records with estral stages randomly grouped showed no significant differences for
      any of the EEG parameters. EEG activity is a sensitive tool to study functional
      changes related to the estral cycle.

PMID- 1382947
TI  - The scalp topography of P300 in the visual and auditory modalities: a comparison
      of three normalization methods and the control of statistical type II error.
AB  - This study was designed to replicate recent findings suggesting that the P3
      component of the event-related potential is dependent on the modality of the
      eliciting stimulus. When assessing this research hypothesis two methodological
      problems are of special interest: first, the amplitudes have to be normalized,
      due to problems with the model of the analysis of variance; second, special care
      has to be taken regarding the beta error, which is the probability of falsely
      accepting the null hypothesis of a statistical test. A possible modality
      independence is associated with the acceptance of a null hypothesis. The first
      problem was assessed by using different normalization procedures and comparing
      their results. The second was solved by controlling the beta error. Results for
      P3 amplitudes from two sessions in which 61 subjects performed in each session an
      auditory and a visual oddball task (EEG measured at 11 locations) showed no
      influence of modality on the P3 elicited by the rare, task relevant, stimulus.
      Influences of modality were observed for the P3 elicited by the frequent
      stimulus. As it is quite unlikely that P3 generating sources are strongly active
      during the processing of the frequent stimulus, this effect is possibly due to a
      component overlap from the vertex potential.

PMID- 1382949
TI  - Dipole modelling of median nerve SEPs in normal subjects and patients with small
      subcortical infarcts.
AB  - Somatosensory evoked potentials (SEPs) to median nerve stimulation were analyzed
      by means of spatio-temporal dipole modelling in 6 normal subjects and 8 patients
      with small infarcts in the thalamo-cortical radiation or thalamus. The SEPs could
      be modelled by a tangentially and a radially oriented equivalent dipole in the
      region of the contralateral cortical hand area and an equivalent dipole located
      in the region of the brain-stem. In 3 patients with absence or reduction of
      amplitudes of cortically generated SEP components, the activity of both cortical
      dipoles was lost or reduced. In 2 patients the frontally recorded SEP component
      P20 was lost; in one of them the activity of mainly the tangential dipole was
      reduced.

PMID- 1382950
TI  - Origin of the widespread N18 in median nerve SEP.
AB  - The widespread N18 potential in median nerve SEP was studied in normal subjects
      and in patients with high cervical, brain-stem and thalamic lesions who had
      profound disturbances of deep sensation. N18 was well identified in the HSi-CV2
      derivation in every normal subject as a broad elevation from the baseline lasting
      about 20 msec. The cortical N20 was absent in all patients. N18 was absent in a
      patient with a dorsal column lesion at C1-2 level. The amplitude and
      configuration of N18 were normal in all other patients with brain-stem and
      thalamic lesions, including a patient with a lesion at the ponto-medullary
      junction. The sagittal distribution of N18 was studied in a patient with a
      thalamic lesion and an oblique distribution with the maximum region between Cz
      and nasion was demonstrated. The present results indicate that at least the
      greater part of N18 is generated at the caudal most brain-stem or through
      branches from this level. Taking previous animal and intraoperative studies into
      consideration, we think it most probable that the main part of N18 corresponds to
      the ventro-rostral negative pole of the dipolar potential generated at the
      cuneate nucleus by the primary afferent depolarization of presynaptic terminals
      of dorsal column fibers.

PMID- 1382951
TI  - Role of SEP in identifying patients requiring temporary shunt during carotid
      endarterectomy.
AB  - EEGs and short-latency somatosensory evoked potentials (SEPs) to median nerve
      stimulation were recorded during 151 carotid endarterectomies, performed under
      general anaesthesia. Carotid occlusion did not affect either EEG or SEP in 120
      cases (group A). In 31 cases the EEG showed "ischaemic" abnormalities (group B).
      A temporary shunt was inserted only in 16 B patients showing also severely
      depressed cortical SEPs within 2 min after carotid occlusion (group B shunt). In
      15 B patients in whom SEPs were less affected, the operation was completed
      without shunt (group B no shunt). One intraoperative stroke occurred in group A
      and two in group B shunt. No neurological complications occurred in group B no
      shunt. Overall stroke rate was 2%. On retrospective analysis, latency and
      amplitude of N20 and P25 waves proved to be uninfluenced by carotid occlusion in
      group A, but were significantly affected in group B shunt. P25 amplitude alone
      was reduced in B no shunt. An arbitrary index (need-for-shunt index, NSI) was
      made in order to rate changes of P25 latency and amplitude. Its mean values were
      significantly different in the 3 groups. A threshold value is suggested above
      which shunt is required, as a useful adjunct to EEG, in order to balance
      prevention of brain ischaemia against the risks of shunt.

PMID- 1382952
TI  - Central sensory and motor conduction in vitamin B12 deficiency.
AB  - Four patients with subacute combined degeneration were studied through upper and
      lower limb SEPs recorded with a non-cephalic reference montage and through
      cortical and spinal magnetic stimulation. Clinical signs were confined to the
      lower limbs in 3 patients; the remaining patient presented only paraesthesiae in
      4 limbs. Median nerve SEPs showed a normal cervical N13 response with a
      significant increase of central conduction time concerning exclusively the P9-P14
      interpeak interval. Central motor conduction to upper and lower limb muscles was
      abnormal. Nerve conduction studies provided no evidence of peripheral nerve
      involvement. These electrophysiological findings suggest that in vitamin B12
      deficiency the higher segments of the cervical cord are usually affected first
      and that central sensory and motor conduction studies are sensitive methods for
      detecting such damage.

PMID- 1382953
TI  - A quantitative method for the assessment of overall effects from a number of
      similar electrophysiological studies: description and application to event
      related potentials in Parkinson's disease.
AB  - Eight comparisons of auditory event-related potentials in idiopathic parkinsonism
      with matched controls were analysed using meta-analytic methods. Overall, there
      was clear evidence that P2, N2, and P3 peak latencies are delayed in patients.
      Effect sizes for the difference between patient and control latencies of N2, and
      to a lesser extent P3, were greater in studies with more cognitively impaired
      patients. High frequency high pass filter settings were significantly associated
      with shorter mean P3 latencies in controls, but not patients, so that greater
      effect sizes tended to be associated with higher high pass cut-off frequencies.
      These results support the argument for using quantitative methods for the review
      of clinical psychophysiological studies.

PMID- 1382954
TI  - Temporal correspondence of intracranial, cochlear and scalp-recorded human
      auditory nerve action potentials.
AB  - Conventional, vertex-ipsilateral ear records ('A'), as well as 3-channel
      Lissajous' trajectories (3-CLTs) of auditory brain-stem evoked potentials (ABEPs)
      were recorded from the scalp simultaneously with tympanic membrane
      electrocochleograms ('TME') and auditory nerve compound action potentials ('8
      AP') recorded intracranially using a wick electrode on the auditory nerve between
      the internal auditory meatus and the brain-stem. The recordings were made during
      surgical procedures exposing the auditory nerve. The peak latency recorded from
      'TME' corresponded to trajectory amplitude peak 'a' of 3-CLT and to peak 'I' of
      the 'A' channel ABEP. Peak latency of '8-AP' was slightly longer than the latency
      of peak 'II' of 'A' when '8-AP' was recorded from the root entry zone and the
      same or shorter when recorded from the nerve trunk. '8-AP' peak latency was
      shorter than trajectory amplitude peak 'b' of 3-CLT regardless of where the wick
      electrode was along the nerve. Peak latencies from all recording sites clustered
      into two distinct groups--those that included N1 from 'TME,' peak 'I' of the 'A'
      record and trajectory amplitude peak 'a' of 3-CLT, and those that included the
      negative peak of '8-AP' and trajectory amplitude peak 'b' of 3-CLT, as well as
      peak 'II' of the 'A' record, when present. In one case, the latency of peak 'II'
      and trajectory amplitude peak 'b' was manipulated by changing the conductive
      properties of the medium surrounding the auditory nerve.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1382955
TI  - Auditory selective attention in middle-aged and elderly subjects: an event
      related brain potential study.
AB  - Reaction times (RTs) and event-related brain potentials (ERPs) were recorded in
      middle-aged (MA) and elderly (ELD) subjects performing an auditory selective
      attention task. Subjects attended to tone bursts of a specified pitch and ear of
      delivery and responded to occasional longer duration target tones (75 vs. 25
      msec). Infrequent novel stimuli (computer synthesized sounds and digitized
      environmental noises) were also included in the stimulus sequence. No significant
      age-related differences were found in the speed or accuracy of target detection.
      However, in both groups, RTs were delayed (by more than 300 msec) to targets that
      followed novel sounds. The prolongation was greater following novel sounds in the
      attended ear, particularly in the ELD group. The effects of selective attention
      on ERPs to standard tones were isolated as negative difference waves (Nds) by
      substracting ERPs to non-attended stimuli from ERPs to the same signals when
      attended. Nds had similar amplitudes, latencies of onset (60 msec), and
      distributions in ELD and MA groups. In both groups, Nd waves were more prominent
      following right ear stimulation, reflecting possible hemispheric asymmetries of
      generators in posterior temporal regions. The mismatch negativity (MMN) was
      isolated by subtracting ERPs to standard tones from ERPs to deviant stimuli. MMN
      amplitudes were reduced in the ELD group. There was also a significant change in
      MMN distribution with age: the MMN was larger over the right hemisphere for MA
      subjects but larger over the left for ELD subjects. Elderly subjects showed a
      trend toward smaller P3 amplitudes and delayed P3 latencies, but group
      differences did not reach statistical significance.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382956
TI  - Neural plasticity in processing of sound location by the early blind: an event
      related potential study.
AB  - Event-related potentials (ERPs) to a change in the locus of origin of a
      repetitive sound were studied in early blind human subjects. It was found that
      the N2b component of the ERP was posteriorly distributed on the scalp to that in
      the sighted control subjects. This suggests that the blind might use, to a larger
      extent than the sighted, parietal, or perhaps even occipital, brain areas in
      sound localization. The present results thus appear to demonstrate plastic
      changes in neural populations involved in processing of auditory space following
      early loss of vision.

PMID- 1382957
TI  - Seasonal affective disorders: the effects of light on human behaviour.
AB  - It has long been recognized that human moods are affected by seasonal changes:
      Hippocrates observed that 'of constitutions some are well or ill adapted to
      summer, others are well or ill adapted to winter'. It is only comparatively
      recently, however, that seasonal affective disorders (SAD) have been the subject
      of serious research. This indicates that mental depression--severe in a small
      minority of cases--may be related to low exposure to light in the winter months.
      In many cases phototherapy--which may influence melatonin production--brings
      relief.

PMID- 1382958
TI  - Prolonged hypoxia induced by the reduction of maternal uterine blood flow alters
      insulin-like growth factor-binding protein-1 (IGFBP-1) and IGFBP-2 gene
      expression in the ovine fetus.
AB  - Insulin-like growth factors (IGF-I and IGF-II) are potent mitogenic and
      differentiating peptides which are synthesized by many fetal tissues. In the
      circulation and tissue fluids, IGFs are bound to binding proteins (BPs) which not
      only function as carrier proteins, but also inhibit or modulate the biological
      actions of IGFs. We have previously shown that prolonged hypoxia in the ovine
      fetus induced by the reduction of maternal uterine blood flow for 24 h causes a
      reduction in the DNA synthesis rate in selected fetal tissues. To determine if
      this effect is due to alterations in the local synthesis of tissue IGFs and their
      binding proteins or to changes in systemic concentrations of IGFs and IGFBPs, we
      have investigated the abundance of mRNAs encoding IGFs and IGFBPs in selected
      tissues and changes in plasma IGFs and IGFBPs. Ovine fetuses (115-120 days
      gestation; n = 6) underwent 24 h of hypoxia by the reduction of maternal uterine
      blood flow (RUBF). Controls (n = 6) underwent the same surgical procedure without
      RUBF. Serial plasma samples were collected before, during, and after the
      experiment, and tissues were collected at the end of 24 h. Mean plasma IGF-I and
      IGF-II concentrations tended to be lower in hypoxic fetuses than in controls
      during the course of hypoxia, but these differences were not statistically
      significant. Tissue mRNA levels for IGF-I and IGF-II in lung, muscle, thymus, and
      kidney were similar in control and hypoxic fetuses after 24 h of hypoxia. The
      relative abundance of liver IGF-I and IGF-II mRNAs was lower in hypoxic fetuses,
      but only IGF-I mRNA levels were significantly different from the control values
      (P < 0.05). Compared to control fetuses, IGFBP-1 mRNA levels in the liver of
      hypoxic fetuses were increased 3- to 7-fold, and IGFBP-1 mRNA expression was
      induced in kidneys of some hypoxic fetuses (two of six). In addition, IGFBP-2
      mRNA levels were decreased in the liver (50%) and kidney (30%) of hypoxic
      fetuses. The increase in liver IGFBP-1 mRNA abundance and the decrease in liver
      and kidney IGFBP-2 mRNA abundance were accompanied by an increase in IGFBP-1
      levels and a decrease in IGFBP-2 levels in fetal plasma. No changes were observed
      in either plasma levels or tissue mRNA abundance for IGFBP-3. Analysis of the
      time course of changes in plasma revealed that the changes in IGFBP-1 and IGFBP-2
      occurred within 4 h of hypoxia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1382959
TI  - Insulin-like growth factor-I (IGF-I) and transforming growth factor-beta 1
      release IGF-binding protein-3 from human fibroblasts by different mechanisms.
AB  - Human neonatal fibroblasts in monolayer culture secrete insulin-like growth
      factor-binding proteins (IGFBPs), which may modulate IGF action. To examine
      whether an increase in extracellular concentrations of IGFBPs in response to IGF
      I is due to the release of cell-associated IGFBPs, we measured secreted and cell
      associated IGFBP-3 immunologically in fibroblast monolayers treated with IGF-I
      and IGF analogs with altered affinities for the IGF receptors and IGFBPs. IGFBP-3
      in medium conditioned by fibroblasts treated with IGF-I was significantly
      increased (P < 0.05) compared with that in medium from untreated cultures;
      concomitantly, cell-associated IGFBP-3 was significantly decreased (P < 0.05).
      [Ser24]IGF-I (reduced affinity for IGF receptors) also increased secreted IGFBP-3
      and decreased cell-associated IGFBP-3. In contrast, IGFBP-3 concentrations in
      medium conditioned by fibroblasts treated with B-chain IGF-I (reduced affinity
      for IGFBPs) were not significantly increased, and cell-associated IGFBP-3 was
      unchanged. Heparin, which releases proteins attached to cell surface
      proteoglycans, increased medium concentrations of IGFBP-3 and decreased IGFBP-3
      binding to fibroblasts. An IGFBP of 29-31 kilodaltons (kDa) showed a pattern of
      regulation similar to that of IGFBP-3, while a third IGFBP, of 24 kDa, was
      decreased in IGF-I- and [Ser24]IGF-I-conditioned medium and unchanged by B-chain
      IGF-I and heparin. Preincubation with transforming growth factor-beta 1 (TGF beta
      1), which stimulates fibroblast IGFBP-3 production, or human serum-derived IGFBP
      3 did not increase cell-associated IGFBP-3. Analysis of total RNA isolated from
      fibroblasts revealed that IGFBP-3 mRNA was increased by TGF beta 1, but not by
      IGF-I. These data suggest that IGFs and TGF beta 1 release fibroblast IGFBPs by
      distinct mechanisms: IGFs by binding and subsequent release of cell-associated
      IGFBP-3 and 29- to 31-kDa IGFBP, and TGF beta 1 by increased de novo synthesis of
      IGFBP-3.

PMID- 1382960
TI  - Nutritional regulation of insulin-like growth factor-binding protein gene
      expression in the ovine fetus and pregnant ewe.
AB  - The factors controlling the synthesis and degradation of the insulin-like growth
      factor-binding proteins (IGFBPs) during pregnancy are poorly understood. To
      clarify the roles of nutritional factors in the regulation of fetal and maternal
      IGFBP production, we examined the effects of fasting, refeeding, and glucose
      administration on plasma IGFBP concentrations and hepatic IGFBP mRNA levels in
      fetal lambs and pregnant ewes (n = 24). Maternal fasting for 3 days in late
      gestation stimulated a 50-100% increase in maternal plasma BP-1 concentrations (P
      < 0.05) and a 2- to 3-fold increase in fetal plasma BP-1 (P < 0.05), as
      determined by densitometric analysis of Western ligand blots. Fasting also
      stimulated a 40-70% increase in maternal plasma BP-2 concentrations (P < 0.05),
      but had no significant effect on fetal plasma BP-2 levels. Levels of hepatic BP-1
      mRNA in the fetus and pregnant ewe during fasting paralleled plasma BP-1 levels,
      suggesting that fasting modulates fetal and maternal plasma BP concentrations at
      least in part through effects on hepatic gene expression. The effects of fasting
      on both mRNA and plasma levels of BP-1 and BP-2 were reversed by 3 days of
      refeeding and were prevented by glucose infusion during fasting. When ewes were
      made hyperglycemic by the infusion of hypertonic glucose, plasma BP-1 and BP-2
      concentrations varied inversely with blood glucose concentrations. In addition,
      hyperglycemia reduced maternal liver BP-1 and BP-2 mRNA levels and fetal BP-1
      mRNA levels by 50-65%. Direct administration of hypertonic glucose to the fetus
      decreased fetal plasma BP-1 levels acutely and reduced fetal BP-1 mRNA levels by
      57%, but had no effect on fetal plasma BP-2 or fetal hepatic BP-2 mRNA levels.
      These findings indicate that glucose and other nutritional factors regulate gene
      expression and plasma levels of BP-1 and BP-2 in the pregnant ewe and BP-1 in the
      fetal lamb. The changes in expression of these IGFBPs during fasting and
      hyperglycemia may play roles in adaptation of the pregnant mother and fetus to
      metabolic stress.

PMID- 1382961
TI  - Down-regulation of messenger ribonucleic acid (mRNA) for the estrogen receptor
      (ER) by phorbol ester requires ongoing RNA synthesis but not protein synthesis.
      Is hormonal control of ER mRNA degradation mediated by an RNA molecule?
AB  - Treatment of MCF-7 cells, a human mammary adenocarcinoma cell line, with the
      phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (10-7 M) was associated
      with a time-dependent reduction in the level of estrogen receptor (ER) mRNA (half
      life approximately 3 h). In the presence of the RNA synthesis inhibitor
      actinomycin D [5.0 micrograms/ml (4.0 microM)], half-life of ER mRNA was much
      longer (approximately 12 h). Furthermore, the TPA-dependent down-regulation of ER
      mRNA was abolished by actinomycin D. Similar effects were observed with 5,6
      dichloro-1-beta-D-ribofuranosylbenzimidazole (150 microM), an inhibitor of RNA
      polymerase. Inhibition of protein synthesis by cycloheximide (50 microM) or
      puromycin [50 micrograms/ml (92 microM)] did not alter the steady state level of
      ER mRNA during a period of 10-12 h. Furthermore, these inhibitors of protein
      synthesis did not prevent the down-regulation of ER mRNA in the presence of TPA.
      Our studies show that degradation of ER mRNA by TPA in MCF-7 cells is dependent
      on ongoing RNA synthesis but not on protein synthesis. This indicates that an RNA
      molecule with rapid turnover, which does not require translation, might be
      involved in the TPA-dependent ER mRNA decay.

PMID- 1382962
TI  - Monoclonal antibodies to the free beta-subunit of human chorionic gonadotropin
      define three distinct antigenic domains and distinguish between intact and nicked
      molecules.
AB  - The present study was designed to characterize monoclonal antibodies (mAbs)
      specific for the free beta-subunit of hCG (free hCG beta), to develop two-site
      immunoradiometric assays (m-IRMAs) specific for free hCG beta, and to study the
      reactivities of various molecular forms of hCG beta in these assays. We attempted
      first to delineate the antigenic regions present specifically on the free hCG
      beta by studying the binding pattern of seven mAbs directed preferentially to hCG
      beta, designated FBT11, P8E, P10F, HB2, P5D, P5H, and INN-64. Competitive
      inhibition experiments performed by RIA demonstrated the specificity of these
      mAbs for the free hCG beta as noncross-reacting with the beta-subunit of human
      (h) LH beta. m-IRMAs were used to analyze the arrangement of epitopes on hCG
      beta. Experiments performed with the seven mAbs used either as capture antibodies
      or radiolabeled indicators confirmed the specificity of the seven mAbs for the
      free hCG beta, and that mAbs FBT11, P8E, and P10F bound to equine LH beta (eLH
      beta), but did not bind to a fragment of hCG beta called the beta-core fragment
      (beta CF). These antibodies defined an antigenic domain identified as A. In
      contrast, mAb HB2 bound neither to eLH beta (e beta) nor to beta CF and was
      directed to domain B (e beta negative, beta CF negative). Finally, mAbs P5D, P5H,
      and INN-64 bound to beta CF, but did not bind to eLH beta, and defined a third
      domain identified as C (e beta negative, beta CF positive). Collectively, these
      results demonstrate that at least six antigenic domains are present on the free
      hCG beta and that a limited set of amino acids was shared among these domains;
      domains A, B, and C are present only on the free beta-subunit, while three other
      domains recognized by mAbs FB19, FBT10, and 518B7 are present on both free hCG
      beta and hCG. Thus, most of the surface of the hCG beta appears to be antigenic
      and accessible to antibody binding. Three different m-IRMAs specific for free hCG
      beta were then constructed using either mAb FBT11 (domain A) or HB2 (domain B).
      The study of the reactivities of various molecular forms of hCG beta in these
      assays demonstrated that the recognition of hCG beta forms nicked at position 43
      (beta 43), 44, and/or 51 (beta 44/51) varied between assays.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1382963
TI  - Insulin-like growth factor-I (IGF-I) and retinoic acid modulation of IGF-binding
      proteins (IGFBPs): IGFBP-2, -3, and -4 gene expression and protein secretion in a
      breast cancer cell line.
AB  - Retinoic acid (RA) blocks insulin-like growth factor-I (IGF-I) stimulation of
      proliferation in the MCF-7 breast carcinoma cell line, and this is associated
      with the appearance of 42- to 46-kilodalton (kDa) IGF-binding proteins(s)
      (IGFBPs) in the conditioned medium (CM), in addition to the approximately 34- and
      27-kDa IGFBPs present in the CM of unstimulated cells. Using immunological,
      biochemical, and molecular biological criteria, we have identified the 27-kDa
      band as IGFBP-4, the 34-kDa band as IGFBP-2, and the 42- to 46-kDa band as IGFBP
      3. IGF-I alone stimulated MCF-7 cell proliferation, and this was associated with
      a large increase in IGFBP-2 in the CM. RA alone resulted in increased IGFBP-4
      levels and the appearance of IGFBP-3 in the CM. The combination of RA and IGF-I,
      which resulted in decreased cellular proliferation, was associated with the
      appearance of IGFBP-3 in the CM at levels far exceeding those seen with RA alone.
      The effect of IGF-I on IGFBP-2 levels and the synergistic action of IGF-I and RA
      on IGFBP-3 levels in CM were blocked by alpha IR3, a monoclonal antibody to the
      human IGF-I receptor, indicating that these effects required signal transduction
      through the IGF-I receptor. IGFBP-2, -3, and -4 mRNAs were detected in
      unstimulated MCF-7 cells. RA increased IGFBP-3 mRNA levels, suggesting that
      transcriptional events contribute to the RA stimulation of IGFBP-3 appearance in
      CM. In contrast, the increase in IGFBP-2 protein in CM after IGF-I treatment
      appeared to be greater than the increase in IGFBP-2 mRNA levels. The increase in
      IGFBP-3 protein in CM in response to the combination of RA and IGF-I was much
      greater than the increase in IGFBP-3 mRNA. These results suggest that the action
      of RA and IGF-I in combination to increase IGFBP-3 protein in CM is principally
      translational or posttranslational. We speculate that RA inhibition of IGF-I
      stimulated MCF-7 cell proliferation may be due to IGFBP-3, or that increased
      levels of IGFBP-3 in response to growth inhibition represent a compensatory
      response.

PMID- 1382964
TI  - Determination of the pharmacokinetic profiles of insulin-like growth factor
      binding proteins-1 and -2 in rats.
AB  - The insulin-like growth factor binding proteins (IGFBPs) are present in serum and
      alter the half-life of IGF-I and II in the vascular compartment. Because both
      IGFBP-1 and 2 have been proposed as regulators of IGF transport, we directly
      determined their distribution and elimination characteristics in rats. 125I-IGFBP
      1 and 2 were injected into anesthetized normal rats. Multiple blood samples were
      drawn over time and the trichloroacetic acid precipitable radioactivity used to
      determine their pharmacokinetic profiles. The mean residence time for IGFBP-1 was
      129 +/- 31 min and for IGFBP-2 116 +/- 24 min. The volume of distribution at
      steady state was 300 +/- 87 ml/kg for IGFBP-1 and 242 +/- 32 ml/kg for IGFBP-2.
      The elimination half-life was 120 +/- 26 min for IGFBP-1 and 144 +/- 32 for IGFBP
      2. The results show that two separate methods of analysis give equivalent results
      for estimation of half-lives of these forms of IGFBPs and that their half-lives
      are substantially greater than that reported for free IGF-I, but less than that
      reported for the 150-kilodalton IGF complex. The findings suggest that these
      proteins equilibrate with extravascular compartments and may have a role in
      modulating transvascular transport of IGF-I and II.

PMID- 1382965
TI  - Screening for hybridomas producing antibodies to steroid hormone receptors:
      interference from phenol red in the hybridoma culture supernates.
AB  - The culture supernates from a variety of mouse hybridomas which were known to
      secrete antibodies to antigens unrelated to steroid hormone receptors were
      examined for routine use as experimental controls for monoclonal anti-oestrogen
      receptor (ER) antibodies. During this process, we made an observation which is
      important for all investigations on monoclonal anti-receptor antibodies. Our
      results indicated that the phenol red dye present in these hybridoma culture
      fluids by binding to the immunoglobulins (Ig) secreted by the hybridoma cells,
      may impart to the Ig-dye complex, a capacity to interact with ER/progesterone
      receptors(PR) which are present in the cytosols or in the sections of ER+ tumors.
      The Ig-dye may thus mimic anti-receptor antibody activity. Growth media
      containing phenol red and Ig-free bovine calf serum supplement or culture fluids
      from a non-Ig secreting hybridoma failed to show similar binding to ER+ tissues.
      This observation documents the need for Ig-dye complex formation to obtain such
      ER-Ig interaction. Complete dialysis of phenol red from the Ig positive
      supernates removed the observed interference of the dye. In this report we
      describe the nature of this interference and the results obtained before and
      after the removal of the dye from Ig+ culture fluids. In addition, we suggest
      some remedial measures that should be considered, while screening and testing the
      specificity of any hybridoma culture product for anti-receptor antibody activity
      (particularly, anti-ER or anti-PR antibodies).

PMID- 1382966
TI  - The embryonic pattern of rat insulin-like growth factor-I gene expression
      suggests a role in induction and early growth of the liver.
AB  - The classic experiments of LeDouarin and her colleagues demonstrated that the
      mesenchymal cells of the septum transversum induce both the rapid proliferation
      of the adjacent endodermally-derived foregut cells and their differentiation into
      the hepatocyte component of the liver. We have used in situ hybridization to test
      whether this inductive activity correlates with the developmental expression of
      genes encoding insulin-like growth factors-I and -II (IGF-I and -II) and/or
      proteins that may mediate IGF action (IGF binding protein-2 and the IGF-I
      receptor). We found that the onset of expression of the transcript for IGF-I in
      the septum transversum correlates precisely with the time that the inductive
      activity appears. In fact, the septum transversum is the earliest site of IGF-I
      mRNA expression detectable in the rat embryo by in situ hybridization.

PMID- 1382968
TI  - Substance P in the synovial membrane and fluid of the equine middle carpal joint.
AB  - This preliminary study was designed to determine whether the neurotransmitter
      substance P was present in the middle carpal synovial membrane of the normal
      horse and whether the neuropeptide could be identified in the synovial fluid of
      normal horses and those with joint diseases. Immunocytochemistry on middle carpal
      synovial membrane biopsies from fresh cadavers was used to demonstrate substance
      P-containing neural elements. Substance P was most abundant in the subintimal
      portion of the membrane, with occasional filaments coursing via synovial fronds
      to the intimal portion. Radioimmunoassay techniques were used on acidified
      acetonitrile-preserved synovial fluid samples to measure substance P
      concentrations. Fluid from 9 joints of 5 normal horses and 6 joints of 4 horses
      with joint diseases were analysed. Disease conditions included acute and chronic
      osteoarthritis and osteochondrosis. Synovia from normal horses contained a mean
      concentration of substance P significantly less than that of horses with joint
      diseases (P less than 0.05). Elevated concentrations of neurotransmitters in
      diseased joints suggests a potential contribution to the pathophysiology of joint
      disorders in horses.

PMID- 1382967
TI  - The properties of ion channels formed by zervamicins.
AB  - The zervamicins (Zrv) are a family of 16 residue peptaibol channel formers,
      related to the 20 residue peptaibol alamethicin (Alm), but containing a higher
      proportion of polar sidechains. Zrv-IIB forms multi-level channels in planar
      lipid (diphytanoyl phosphatidylcholine) bilayers in response to cis positive
      voltages. Analysis of the voltage and concentration dependence of macroscopic
      conductances induced by Zrv-IIB suggests that, on average, channels contain ca.
      13 peptide monomers. Analysis of single channel conductance levels suggests a
      similar value. The pattern of successive conductance levels is consistent with a
      modified helix bundle model in which the higher order bundle are distorted within
      the plane of the bilayer towards a "torpedo" shaped cross-section. The kinetics
      of intra-burst switching between adjacent conductance levels are shown to be
      approximately an order of magnitude faster for Zrv-IIB than for Alm. The channel
      forming properties of the related naturally occurring peptaibols, Zrv-Leu and Zrv
      IC, have also been demonstrated, as have those of the synthetic apolar analogue
      Zrv-Al-16. The experimental studies on channel formation are combined with the
      known crystallographic structures of Zrv-Al-16 and Zrv-Leu to develop a molecular
      model of Zrv-IIB channels.

PMID- 1382969
TI  - Polyacrylamide gel electrophoresis in vertical, inverse and double-crossing
      gradients of soluble polymers.
AB  - The presence of soluble dextrans, methylcellulose and polyethylene glycol
      polymers incorporated into vertical sodium dodecyl sulfate (SDS)-polyacrylamide
      slabs during electrophoresis can have a pronounced effect on protein separations.
      The effects of various standard and inverse gradients of polymers on the
      electrophoretic mobility of marker proteins in 10% T, 2.66% C Laemmli-style SDS
      gels, and the effects of simultaneous pore size and polymer gradients were
      investigated. These experiments demonstrate that the inclusion of polymers is a
      new, additional parameter that can be useful in resolving complex mixtures of
      proteins.

PMID- 1382970
TI  - A rapid and efficient method for the screening of acid phosphatase 1 in young
      tomato seedlings, and for the identification of root-knot nematode species using
      miniaturized polyacrylamide gel electrophoresis.
AB  - A relatively rapid and highly sensitive miniaturized polyacrylamide gel
      electrophoresis technique is described for the analysis of certain isozymes from
      single cotyledons of tomato seedlings and from single females of the root-know
      nematode (Meloidogyne spp.). Homogenates from single tomato cotyledons (7, 14,
      21, and 28 days old) were electrophoresed and stained for acid phosphatase 1 (Aps
      1) activity. Cotyledons from plants of all the above age groups showed good Aps 1
      activity. Nondestructive screening for tomato Aps 1 is therefore feasible, using
      very small samples, from as young as 7-day-old tomato seedlings. This could be of
      important use in expediting root-knot nematode resistance (based on the Aps 1
      linked resistance gene Mi) screening for breeding programs, or F1 testing for
      seed production purposes. In addition, the mini-polyacrylamide gel
      electrophoresis technique was useful for determination of the Aps 1 allelic
      contribution to the total enzyme activity. The system was also used to detect
      malate dehydrogenase and esterase isozyme activity from single adult females of
      the four common root-knot nematodes, Meloidogyne arenaria, M. hapla, M.
      incognita, and M. javanica, with equally good results, enabling species
      discrimination.

PMID- 1382971
TI  - Gel electrophoretic analysis of chitosan hydrolysis products.
AB  - Enzymatic hydrolysis of commercial crustacean chitosan by barley chitosanases was
      analyzed by subjecting chitosan to electrophoresis in a 10% w/v polyacrylamide
      slab gel in the presence of 7 M urea and 5.5% v/v acetic acid. Chitosan migrated
      as a polycation. Chitosan was stained with Coomassie Brilliant Blue R-250 or
      visualized by ultraviolet transillumination after staining with Calcofluor White
      M2R. Some chitosan molecules were retarded by gel electrophoresis while small
      chitosan molecules migrated at the bottom of a 10% w/v polyacrylamide gel. Such
      analysis revealed that 96 h were necessary to convert all chitosan to
      oligosaccharides under our assay conditions. Chitosan oligosaccharides generated
      by enzymatic or chemical hydrolysis were further analyzed by electrophoresis in a
      33% w/v polyacrylamide gel containing urea and acetic acid. Coomassie Brilliant
      Blue R-250 was found to be better than Calcofluor White M2R for staining chitosan
      oligosaccharides. Chitosan oligomers of four residues (tetramers) or more were
      easily resolved in such a polyacrylamide gel system. To our knowledge, this is
      the first report of a gel electrophoretic separation of chitosan and its
      oligosaccharides.

PMID- 1382972
TI  - Inter-alpha-trypsin inhibitor polymorphism in African blacks.
AB  - The inter-alpha-trypsin inhibitor (ITI) polymorphism was analyzed in an African
      Negroid population using polyacrylamide gel isoelectric focusing and subsequent
      immunoblotting. Gene frequencies of ITI*1, ITI*2, ITI*3 and ITI*4 were calculated
      to be 0.564, 0.083, 0.337 and 0.004, respectively. One unknown rare allele,
      ITI*6, determines further phenotypes in combination with the alleles ITI*1 and
      ITI*3. Gene frequency of ITI*6 was calculated to be 0.012. The common alleles are
      represented by ITI*1 and ITI*3. The allele distribution is therefore different
      from European and Asian populations.

PMID- 1382973
TI  - Absence of cortical white matter changes in three patients undergoing long-term
      vigabatrin therapy.
AB  - Chronic administration of the experimental antiepileptic drug vigabatrin (gamma
      vinyl GABA) to animals has been shown to cause dose-dependent neuropathological
      changes characterized by a microvacuolation in specific white matter tracts. This
      finding has led to some concern as to whether similar pathologic changes might
      occur in patients taking this medication. Here we report on analysis of tissue
      specimens taken during neurosurgery from three patients undergoing chronic
      vigabatrin therapy (4 g/day). The first patient, a 34-year-old woman, had taken
      vigabatrin for 2 years prior to surgery, the second, a 50-year-old man, had taken
      the drug for 1 year, and a 34-year-old man had taken the drug for 5.3 years. For
      comparison, similar specimens were taken from three other patients not taking
      vigabatrin who were undergoing surgery for intractable epilepsy. Specimens from
      each subject were prepared in an identical manner and examined with light and
      electron microscopy. All specimens were examined in a blinded fashion. There was
      some minor nonspecific myelinic splitting seen in both controls and vigabatrin
      treated patients but there was no evidence for any drug-induced lesions similar
      to that seen in experimental animals.

PMID- 1382974
TI  - A mammalian dual specificity protein kinase, Nek1, is related to the NIMA cell
      cycle regulator and highly expressed in meiotic germ cells.
AB  - Screening of mouse cDNA expression libraries with antibodies to phosphotyrosine
      resulted in repeated isolation of cDNAs that encode a novel mammalian protein
      kinase of 774 amino acids, termed Nek1. Nek1 contains an N-terminal protein
      kinase domain which is most similar (42% identity) to the catalytic domain of
      NIMA, a protein kinase which controls initiation of mitosis in Aspergillus
      nidulans. In addition, both Nek1 and NIMA have a long, basic C-terminal
      extension, and are therefore similar in overall structure. Despite its
      identification with anti-phosphotyrosine antibodies, Nek1 contains sequence
      motifs characteristic of protein serine/threonine kinases. The Nek1 kinase
      domain, when expressed in bacteria, phosphorylated exogenous substrates primarily
      on serine/threonine, but also on tyrosine, indicating that Nek1 is a dual
      specificity kinase with the capacity to phosphorylate all three hydroxyamino
      acids. Like NIMA, Nek1 preferentially phosphorylated beta-casein in vitro. In
      situ RNA analysis of nek1 expression in mouse gonads revealed a high level of
      expression in both male and female germ cells, with a distribution consistent
      with a role in meiosis. These results suggest that Nek1 is a mammalian relative
      of the fungal NIMA cell cycle regulator.

PMID- 1382976
TI  - Identification and modulation of a voltage-dependent anion channel in the plasma
      membrane of guard cells by high-affinity ligands.
AB  - Guard cell anion channels (GCAC1) catalyze the release of anions across the
      plasma membrane during regulated volume decrease and also seem to be involved in
      the targeting of the plant growth hormones auxins. We have analyzed the
      modulation and inhibition of these voltage-dependent anion channels by different
      anion channel blockers. Ethacrynic acid, a structural correlate of an auxin,
      caused a shift in activation potential and simultaneously a transient increase in
      the peak current amplitude, whereas other blockers shifted and blocked the
      voltage-dependent activity of the channel. Comparison of dose-response curves for
      shift and block imposed by the inhibitor, indicate two different sites within the
      channel which interact with the ligand. The capability to inhibit GCAC1 increases
      in a dose-dependent manner in the sequence: probenecid less than A-9-C less than
      ethacrynic acid less than niflumic acid less than IAA-94 less than NPPB. All
      inhibitors reversibly blocked the anion channel from the extracellular side.
      Channel block on the level of single anion channels is characterized by a
      reduction of long open transitions into flickering bursts, indicating an
      interaction with the open mouth of the channel. IAA-23, a structural analog of
      IAA-94, was used to enrich ligand-binding polypeptides from the plasma membrane
      of guard cells by IAA-23 affinity chromatography. From this protein fraction a 60
      kDa polypeptide crossreacted specifically with polyclonal antibodies raised
      against anion channels isolated from kidney membranes. In contrast to guard
      cells, mesophyll plasma membranes were deficient in voltage-dependent anion
      channels and lacked crossreactivity with the antibody.

PMID- 1382975
TI  - VCP, the mammalian homolog of cdc48, is tyrosine phosphorylated in response to T
      cell antigen receptor activation.
AB  - Activation of T cells through the T cell antigen receptor (TCR) results in the
      rapid tyrosine phosphorylation of a number of cellular proteins, one of the
      earliest being a 100 kDa protein. We have sought to identify this 100 kDa
      substrate by partially purifying the protein by antiphosphotyrosine (APT)
      affinity purification, in order to obtain amino acid sequence data and, using
      this information, to isolate the cDNA clone encoding the molecule. We report here
      that the amino acid sequence data showed pp100 to be the murine equivalent of
      porcine valosin containing protein (VCP), a finding confirmed from the cloning
      and sequencing of the murine pp100 cDNA. Sequence analysis has shown VCP to be a
      member of a family of ATP binding, homo-oligomeric proteins, and the mammalian
      homolog of Saccharomyces cerevisiae cdc48p, a protein essential to the completion
      of mitosis in yeast. We also provide proof that both endogenous and expressed
      murine VCP are tyrosine phosphorylated in response to T cell activation. Thus we
      have identified a novel component of the TCR mediated tyrosine kinase activation
      pathway that may provide a link between TCR ligation and cell cycle control.

PMID- 1382977
TI  - Delineation of structural domains involved in the subtype specificity of
      tachykinin receptors through chimeric formation of substance P/substance K
      receptors.
AB  - The mammalian tachykinin receptors belong to the family of G protein-coupled
      receptors and consist of the substance P, substance K and neuromedin K receptors
      (SPR, SKR and NKR). We constructed 14 chimeric receptors in which seven
      transmembrane segments were sequentially exchanged between the rat SPR and SKR
      and examined the subtype specificity of the chimeric receptors by radioligand
      binding and inositol phosphate measurements after transfection into COS cells.
      All chimeric receptors showed maximum responses in agonist-induced inositol
      phosphate stimulation. Detailed analysis of five receptors with agonist
      selectivity similar to SPR indicated that the selectivity is mainly determined by
      the region extending from transmembrane segment II to the second extracellular
      loop together with a minor contribution of the extracellular N-terminal portion.
      This conclusion was more directly confirmed by an additional chimeric formation
      in which the introduction of the above middle portion of SPR into the
      corresponding region of SKR conferred a high affinity binding to substance P. The
      tachykinin receptors can thus be divided into two functional domains: the region
      covering transmembrane segments V-VII and responsible for fundamental recognition
      of the common tachykinin sequence; and its preceding portion involved in evoking
      subtype specificity by interacting with the divergent sequences of the peptides.

PMID- 1382978
TI  - 7-2/MRP RNAs in plant and mammalian cells: association with higher order
      structures in the nucleolus.
AB  - Mammalian MRP (for mitochondrial RNA processing) RNA, also known as 7-2 RNA, is a
      nuclear encoded small RNA which has been reported to function in two different
      cellular compartments: in the mitochondria and in the nucleus. The
      ribonucleoprotein particle which contains the 7-2/MRP RNA, called RNase MRP, has
      ribonucleolytic activity and shares some structural similarity with RNase P. It
      has been proposed that in mitochondria, the RNase MRP is responsible for
      endonucleolytic cleavage of primer RNA during DNA replication. We have
      characterized the gene and cDNAs encoding 7-2/MRP-like RNA in Arabidopsis and
      tobacco, and found that in plants this RNA is enriched in nucleoli but is
      undetectable in purified mitochondria isolated from tobacco leaves or cells grown
      in suspension. In glycerol gradients tobacco 7-2/MRP RNA cosediments with large
      approximately 80S structures possibly representing ribosomal precursors.
      Fractionation of HeLa cells has also revealed that 7-2/MRP resides in the
      nucleolus and that most of it is associated with complexes sedimenting at
      approximately 80S, similar to those containing the U3 nucleolar RNA which is
      known to participate in pre-rRNA processing. These results indicate that the 7
      2/MRP ribonucleoparticle may be involved in ribosome biogenesis, in both plant
      and mammalian cells.

PMID- 1382979
TI  - Silent mitochondrial and active nuclear genes for subunit 2 of cytochrome c
      oxidase (cox2) in soybean: evidence for RNA-mediated gene transfer.
AB  - In most plants and other eukaryotes investigated, the mitochondrial genome
      carries the gene encoding subunit 2 of cytochrome c oxidase (cox2). In this
      paper, we show that the previously reported mitochondrial cox2 of soybean is
      actually silent, and that there is an expressed, single-copy, nucleus-encoded
      cox2. Molecular cloning and sequence analysis of cox2 cDNA and genomic clones
      show that the soybean nuclear gene encodes an N-terminal extension that resembles
      a signal sequence for mitochondrial import and whose coding sequence is separated
      by an intron from that corresponding to mtDNA-encoded cox2. Comparison of soybean
      mitochondrial and nuclear cox2 sequences clearly indicates that in an ancestor of
      soybean, cox2 was transferred from the mitochondrion to the nucleus via a C-to-U
      edited RNA intermediate.

PMID- 1382980
TI  - Molecular cloning and characterization of iojap (ij), a pattern striping gene of
      maize.
AB  - Iojap (ij) is a recessive striped mutant of maize affecting the development of
      plastids in a local and position-dependent manner on the leaves. The ij-affected
      plastids are transmitted to some of the progeny even when the function of the
      nuclear gene is restored. Developmental defects during embryogenesis and leaf
      proliferation are other phenotypic characteristics of ij. The extent of striping
      and the degree of developmental arrest in ij depend upon genetic background. To
      understand the diverse and unique phenotypic expression of ij, a transposon
      tagging experiment has been conducted using Robertson's Mutator (Mu). A new ij
      mutant was obtained from crosses of the reference allele of (ij-ref) to Mu lines.
      Subsequent genetic and molecular studies showed that the mutant carried a new ij
      allele (ij-mum1) from the Mu lines and contained a Mu1 element that cosegregated
      with the iojap phenotype. A 6.0 kb EcoRI genomic DNA fragment containing the Mu1
      element was cloned. ij-ref is unstable, and revertants (Ij-Rev) have been
      obtained. Using the flanking DNA from the genomic clone as a probe, DNA
      polymorphisms were detected between ij-ref and these revertants. Further,
      transcripts were restored to the normal level in Ij-Rev seedlings. Comparison of
      genomic DNA clones from ij-ref, ij-mum1 and Ij indicated that the ij-ref allele
      contained 1.5 kb of additional DNA related to a transposable element, Ds.
      Germinal and somatic revertant alleles were derived by excision of this 1.5 kb
      element from ij-ref. The structure of the Ij gene and the DNA sequence of its
      transcribed region were determined. The Ij gene encodes a 24.8 kDa protein that
      showed no significant sequence similarity with proteins listed in databases.

PMID- 1382981
TI  - Temporal coordination of regulatory gene expression by the steroid hormone
      ecdysone.
AB  - In Drosophila, pulses of the steroid hormone ecdysone function as temporal
      signals that trigger the major postembryonic developmental transitions. The best
      characterized of these pulses activates a series of puffs in the polytene
      chromosomes as it triggers metamorphosis. A small set of early puffs is induced
      as a primary response to the hormone. These puffs encode regulatory proteins that
      both repress their own expression and activate a large set of late secondary
      response genes. We have used Northern blot analysis of RNA isolated from staged
      animals and cultured organs to study the transcription of three primary response
      regulatory genes, E75, BR-C and EcR. Remarkably, their patterns of transcription
      in late larvae can be defined in terms of two responses to different ecdysone
      concentrations. The class I transcripts (E74B and EcR) are induced in mid-third
      instar larvae in response to the low, but increasing, titer of ecdysone. As the
      hormone concentration peaks in late third instar larvae, these transcripts are
      repressed and the class II RNAs (E74A, E75A and E75B) are induced. The BR-C RNAs
      appear to have both class I and class II characteristics. These data demonstrate
      that the relatively simple profile of a hormone pulse contains critical temporal
      information that is transduced into waves of primary response regulatory gene
      activity.

PMID- 1382982
TI  - Mobilization of circulating leucocyte and lymphocyte subpopulations during and
      after short, anaerobic exercise.
AB  - A group of 11 healthy athletes [age, 27.4 (SD 6.7) years; body mass, 75.3 (SD
      9.2) kg; height, 182 (SD 8) cm; maximal oxygen uptake, 58.0 (SD 9.9) ml.kg-1.min
      1] conducted maximal exercise of 60-s duration on a cycle ergometer [mean
      exercise intensity, 520 (SD 72) W; maximal lactate concentration, 12.26 (SD 1.35)
      mmol.l-1]. Adrenaline and noradrenaline, and leucocyte subpopulations were
      measured flow cytometrically at rest, after 5-min warming up at 50% of each
      individual's anaerobic threshold (followed by 5-min rest), immediately after (0
      min), 15 min, 30 min, and 1, 2, 4 and 24 h after exercise. Granulocytes showed
      two increases, the first at 15 min and, after return to pre-exercise values, the
      second more than 2 h after exercise. Eosinophils also increased at 15 min but
      decreased below pre-exercise values 2 h after exercise. Total lymphocytes and
      monocytes had their maximal increases at 0 min. Out of all lymphocyte
      subpopulations CD3-CD16/CD56(+)- and CD8+CD45RO--cells increased most and had
      their maximal cell counts at 0 min. The CD3(+)-, CD4+CD45RO(+)-, CD8+CD45RO(+)-,
      and CD19(+)- increased at 0 min, but had their maximum at 15 min. During the
      hours after exercise CD3-CD16/CD56(+)-, CD3+CD16/CD56(+)-, CD8+CD45RO(+)- and
      CD8+CD45RO--cells were responsible for the lymphocytopenia. The CD3(+)- and CD3
      CD16/CD56(+)-cells were lower 24 h after exercise than before exercise.
      Adrenaline and noradrenaline increased during exercise. In conclusion, short
      anaerobic exercise led to a sequential mobilization of leucocyte subpopulations.
      The rapid increase of natural killer cells and monocytes may have been due to
      increased blood flow and catecholamine concentrations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1382983
TI  - Purification and characterization of a rat liver protein-tyrosine phosphatase
      with sequence similarity to src-homology region 2.
AB  - Utilizing three proteins plus tyrosine-glutamate copolymer as substrates, all of
      which are subjected to (near) stoichiometrical phosphorylation exclusively on
      tyrosine residues, we partially purified four different protein-tyrosine
      phosphatases (PTPases) from rat liver cytosol which differed in substrate
      preference. Of the four PTPases, tentatively termed L1, L2, L3, and L4, PTPase L1
      was purified to apparent homogeneity by a procedure involving chromatography on
      DEAE-cellulose at pH 7.0, Blue Sepharose, DEAE-cellulose at pH 7.6,
      hydroxyapatite, Phenyl Sepharose, Mono Q, and TSKgel Heparin. PTPase L1 was
      purified about 7000-fold from the extract and 0.27 mg was isolated from 1000 g
      liver corresponding to a yield of 13% from the Blue Sepharose step where it had
      become freed from any other PTPases detectable by our assay procedure. The
      purified PTPase L1 showed a major protein band of 67 kDa on SDS/PAGE.
      Catalytically, PTPase L1 had a specific activity of about 6500 nmol Pi released
      min-1mg-1 toward tyrosine-glutamate copolymer phosphorylated on tyrosine
      residues. PTPase L1 exhibited very low sensitivities to PTPase inhibitors such as
      zinc acetate, sodium vanadate, and acidic compounds as compared with those of
      most of the PTPases purified thus far. Amino acid sequence analysis of the
      purified PTPase L1 revealed a partial peptide sequence showing similarity to the
      catalytic domain core sequences conserved in the PTPase family. PTPase L1 was
      most similar to a PTPase termed PTP1C encoded by a human breast carcinoma cDNA
      but the identity was 55% over 117 residues spanning nearly half of the catalytic
      domain of PTP1C. The analysis also revealed another partial peptide sequence (113
      residues) 70% identical with the sequence corresponding to 68% of two adjacent
      copies of the src homology region 2(SH-2 domain) identified in PTP1C. Besides
      those peptide sequences, PTPase L1 had regional sequences which were 70-90%
      identical with the residues lying between the two SH-2 domains or between the
      more C-terminal SH-2 domain and the catalytic domain of the carcinoma PTPase.

PMID- 1382984
TI  - Effects of selective inhibition of cathepsin B and general inhibition of cysteine
      proteinases on lysosomal proteolysis in rat liver in vivo and in vitro.
AB  - Intraperitoneal administration of N-(L-trans-propylcarbamoyloxirane-2-carbonyl)-L
      isoleucyl-L-prolin e (CA-074) to rats at a dose of 4 mg/100 g greatly inhibited
      cathepsin-B activity in both liver and kidney for at least 4 h. Its inhibitory
      effect was selective for cathepsin-B activity in the liver but not in the kidney.
      The effects of selective inhibition of cathepsin-B activity by CA-074 treatment,
      and general inhibition of cysteine proteinases by N-(L-3-trans-carboxyoxirane-2
      carbonyl)-L-leucyl-3-methylbutylamid e (E-64-c) on the degradation of fluorescein
      isothiocyanate (FITC)-labeled asialofetuin in liver lysosomes, were examined in
      vivo. Undegraded or partially degraded FITC-labeled asialofetuin and its FITC
      labeled degradation products were both found in the lysosomes and were easily
      separated by Sephadex G-25' column chromatography. The FITC-labeled degradation
      products were mainly lysine with an FITC-labeled epsilon-amino group.
      Accumulation of undegraded or partially degraded FITC-labeled asialofetuin in the
      lysosomes was marked after E-64-c treatment, but slight after CA-074 treatment.
      Under the marked inhibition of general lysosomal cysteine-proteinase activity by
      E-64-c or marked selective inhibition of cathepsin-B activity by CA-074 in vitro,
      degradation of FITC-labeled asialofetuin by disrupted lysosomes was analyzed on
      the basis of measurement of FITC-labeled degradation products by Sephadex G-25
      column chromatography. It was suppressed markedly but incompletely by E-64-c as
      well as by CA-074, but more weakly than by E-64-c. These results shows that E-64
      sensitive cysteine proteinases are important in lysosomal protein degradation,
      but cathepsin B has only a role in part and that an E-64-resistant proteinase(s)
      may also be important.

PMID- 1382986
TI  - Interaction between bovine trypsin and a synthetic peptide containing 28 residues
      of the bait region of human alpha 2-macroglobulin.
AB  - The time course of the interaction between trypsin and a synthetic peptide
      corresponding to a segment (residues 676-703) of the bait region (residues 666
      706) of human alpha 2-macroglobulin (alpha 2M) was studied by measuring the
      generation of cleavage products as a function of time by HPLC. Three primary
      cleavage sites for trypsin were present in the synthetic peptide. The fastest
      cleavage occurred at the bond corresponding to Arg696-Leu in alpha 2M with an
      estimated kcat/Km = 1-2 x 10(6) M-1.s-1. This value is of the same magnitude as
      that characterizing the interaction of alpha 2M and trypsin when taking into
      account the fact that alpha 2M is a tetramer, kcat/Km = 5 x 10(6) M-1.s-1
      [Christensen, U. & Sottrup-Jensen, L. (1984) Biochemistry 23, 6619-6626]. The
      values of kcat/Km for cleavage at bonds corresponding to Arg681-Val and Arg692
      Gly in alpha 2M were 1.5 x 10(5) M-1.s-1 and 1.3 x 10(5) M-1.s-1, respectively.
      Cleavage of intermediate product peptides was slower, with kcat/Km in the range
      13-1.3 x 10(6) M-1.s-1. The value of Km determined for fast cleavage in the
      synthetic peptide was 8-10 microM. 1H-NMR spectroscopy indicated no ordered
      structure of the peptide. Hence, the very fast cleavage of the peptide is
      compatible with a loose structure that readily adopts a conformation favorable
      for recognition and cleavage by trypsin.

PMID- 1382985
TI  - Release of 14-kDa group-II phospholipase A2 from activated mast cells and its
      possible involvement in the regulation of the degranulation process.
AB  - Group II phospholipase A2 was detected in appreciable amounts in rat peritoneal
      mast cells. The effect of several inhibitors specific to 14-kDa group-II
      phospholipase A2, including two proteinaceous inhibitors and a product of
      microorganisms with a low molecular mass, on mast-cell activation was examined.
      When rat peritoneal mast cells were sensitized with IgE and then challenged with
      antigen, the specific phospholipase-A2 inhibitors suppressed histamine release in
      a concentration-dependent manner. By contrast, these inhibitors showed no effect
      on prostaglandin generation under the same conditions. Histamine release from rat
      peritoneal mast cells subjected to non-immunochemical stimuli, such as
      concanavalin A, the Ca2+ ionophore A23187, compound 48/80 and substance P was
      also suppressed. When rat peritoneal mast cells were treated with 14-kDa-group-II
      phospholipase-A2-specific inhibitors, washed and stimulated, histamine release
      was not affected appreciably. Similar suppressive effects of the inhibitors on
      histamine release were observed with mouse cultured bone-marrow-derived mast
      cells. When bone-marrow-derived mast cells were activated, they secreted both a
      soluble and an ecto-enzyme form of 14-kDa group-II phospholipase A2, although
      appearance of the enzyme associated with the external surface of cells was
      observed transiently. An appreciable amount of membrane phospholipids was
      degraded during activation of mast cells, which was decreased by treatment with
      14-kDa-group-II-phospholipase-A2 inhibitor. These observations suggest that
      degranulation and eicosanoid generation in mast cells are regulated independently
      by discrete phospholipases A2 and that the 14-kDa group-II phospholipase A2
      released from mast cells during activation may play an essential role in the
      progression of the degranulation process.

PMID- 1382987
TI  - Angiogenesis and angiogenesis inhibitors in paediatric diseases.
AB  - Angiogenesis, the generation of new capillaries from existing blood vessels, is
      rarely observed in the healthy organism, but can present during various
      paediatric diseases. In this review, we describe recent progress in the
      understanding of pathological angiogenesis and approaches for an improved therapy
      of angiogenic childhood diseases.

PMID- 1382988
TI  - Correlation of calcineurin phosphatase activity and programmed cell death in
      murine T cell hybridomas.
AB  - Ligation of T cell receptor/CD3 complexes induces programmed cell death, or
      apoptosis, in immature thymocytes and many T cell hybridomas. While it has been
      demonstrated that T cell receptor-mediated apoptosis requires an increase in
      intracellular calcium concentration, the specific calcium-dependent signalling
      events leading to cell death are poorly defined. We have previously shown that T
      cell receptor/CD3-mediated induction of apoptosis in a murine T cell hybridoma is
      inhibited by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Recently,
      it has been determined that these agents inhibit the activity of calcineurin, a
      calcium- and calmodulin-dependent serine/threonine phosphatase. Using an assay
      which measures calcineurin activity in cell lysates, we find that calcineurin
      dependent dephosphorylation of a phosphopeptide substrate is potently inhibited
      in hybridomas treated with CsA or FK506. Drug dose-response analyses indicate
      that the level of cellular calcineurin activity correlates closely with the
      ability of these cells to undergo apoptosis. Thus, calcineurin appears to be a
      critical mediator of T cell receptor/CD3 signalling leading to programmed cell
      death in T cell hybridomas.

PMID- 1382989
TI  - Evidence for endocytosis of E-selectin in human endothelial cells.
AB  - E-selectin is an inducible adhesion molecule on endothelial cells. The
      internalization of this glycoprotein was investigated on tumor necrosis factor
      (TNF)-activated cultured human umbilical vein endothelial cells (HUVEC). Kinetics
      of intercellular adhesion molecule-1 (ICAM-1) were studied in parallel
      experiments. Internalization studies were performed with radioiodinated
      antibodies in an acid elution endocytosis assay, and by immunohistology; both
      approaches gave equivalent results. [125I]ENA1, a monoclonal antibody (mAb)
      specific for E-selectin, was internalized at a rate of approximately 1.7% of the
      membrane-bound [125I]mAb per minute. In contrast, less than 0.1% of membrane
      bound [125I]RR1/1, an mAb specific for ICAM-1, was internalized per minute. TNF
      activated HUVEC were immunostained and examined by light microscopy (LM) and
      electron microscopy (EM). LM revealed the presence of ENA1, but not RR1/1, after
      30 minutes of incubation with these mAb in cytoplasmic vesicles, which were
      characterized as multivesicular bodies by EM. Without previous mAb exposure of
      the endothelial cells, both high amounts of E-selectin and bovine serum albumin
      complexed to colloidal gold, used as a marker for fluid-phase internalization,
      were detected in the same organelles, thus arguing against mAb interaction
      induced E-selectin internalization. Furthermore, the amount of E-selectin surface
      expression was not influenced by ongoing mAb presence, also arguing against mAb
      interference with normal E-selectin kinetics. Taken together, these results
      indicate that TNF-activated HUVEC constitutively internalize E-selectin.
      Physiological significance of E-selectin internalization in the regulation of E
      selectin membrane expression, and in clearing E-selectin ligands from the
      circulation, needs further investigation.

PMID- 1382990
TI  - The importance of cross-linking in the homotypic aggregation of lymphocytes
      induced by anti-leukosialin (CD43) antibodies.
AB  - Leukosialin (CD43) is a major glycoprotein of T lymphocytes which has an
      extracellular domain of 45 nm in length that is heavily O-glycosylated.
      Monoclonal antibodies (mAb) to the extracellular domain of human leukosialin
      induce aggregation of T lymphocytes, monocytes and some cell lines that express
      leukosialin. The aggregation was reported in one case to be inducible by Fab
      fragments. In the present study, nine mAb specific for rat leukosialin were
      tested as inducers of thymocyte aggregation and all were effective. The level of
      aggregation was reduced by metabolic and cytoskeletal inhibitors, by removal of
      divalent cations and by reducing the temperature from 37 degrees C to 4 degrees
      C. The aggregation produced by mAb specific for certain epitopes was less
      sensitive to these inhibitors than aggregation induced by mAb to other epitopes.
      To examine the requirement for cross-linking, Fab fragments of four of the
      antibodies were tested and found to be inactive except for those derived from the
      OX75 mAb. However, OX75 Fab showed a tendency to dimerize, and monomeric OX75 Fab
      obtained directly after gel filtration was unable to induce aggregation. Thus
      induction of rat thymocyte aggregation by anti-leukosialin antibodies requires
      bivalent cross-linking and maximal aggregation is dependent on energy and an
      intact cytoskeleton. Mechanisms of antibody-induced aggregation are considered
      and it is proposed that in the case of leukosialin the antibodies may cross-link
      cells to overcome inherent repulsion between them and that subsequently other
      adhesion molecules complete the clustering process.

PMID- 1382991
TI  - Activated human T cells express a ligand for the human B cell-associated antigen
      CD40 which participates in T cell-dependent activation of B lymphocytes.
AB  - To identify the ligand for the B cell-associated antigen CD40, we constructed a
      chimeric immunoglobulin molecule where the extracellular portion of the CD40
      protein replaced the normal immunoglobulin variable region. No binding was
      detected on resting peripheral blood T cells. However, following T cell
      activation with phorbol esters and ionomycin, the chimeric protein bound
      specifically to activated human T cells and precipitated a 35-kDa protein from
      such cells. The induction of the CD40 ligand was detectable on the cell surface
      after 1 h, with maximal expression after 8 h of stimulation. The T cells
      expressing CD40 ligand were predominantly CD4 positive, although a proportion of
      CD8-positive cells also expressed the protein. There was no particular
      correlation with CD45 phenotype. Finally, we found that soluble CD40 inhibited T
      dependent B cell proliferation. The results are discussed in the context of
      cognate interactions between B and T cells.

PMID- 1382992
TI  - Evolution of vertebrate IgM: complete amino acid sequence of the constant region
      of Ambystoma mexicanum mu chain deduced from cDNA sequence.
AB  - cDNA clones coding for the constant region of the Mexican axolotl (Ambystoma
      mexicanum) mu heavy immunoglobulin chain were selected from total spleen RNA,
      using a cDNA polymerase chain reaction technique. The specific 5'-end primer was
      an oligonucleotide homologous to the JH segment of Xenopus laevis mu chain. One
      of the clones, JHA/3, corresponded to the complete constant region of the axolotl
      mu chain, consisting of a 1362-nucleotide sequence coding for a polypeptide of
      454 amino acids followed in 3' direction by a 179-nucleotide untranslated region
      and a polyA+ tail. The axolotl C mu is divided into four typical domains (C mu 1
      C mu 4) and can be aligned with the Xenopus C mu with an overall identity of 56%
      at the nucleotide level. Percent identities were particularly high between C mu 1
      (59%) and C mu 4 (71%). The C-terminal 20-amino acid segment which constitutes
      the secretory part of the mu chain is strongly homologous to the equivalent
      sequences of chondrichthyans and of other tetrapods, including a conserved N
      linked oligosaccharide, the penultimate cysteine and the C-terminal lysine. The
      four C mu domains of 13 vertebrate species ranging from chondrichthyans to
      mammals were aligned and compared at the amino acid level. The significant number
      of mu-specific residues which are conserved into each of the four C mu domains
      argues for a continuous line of evolution of the vertebrate mu chain. This notion
      was confirmed by the ability to reconstitute a consistent vertebrate evolution
      tree based on the phylogenic parsimony analysis of the C mu 4 sequences.

PMID- 1382994
TI  - Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the
      HRF20 (CD59) gene.
AB  - HRF20 (CD59) is a membrane glycoprotein which protects cells from the membrane
      attack reaction of homologous complement. A patient who is completely deficient
      in HRF20 expression and is suffering from paroxysmal nocturnal hemoglobinuria
      (PNH) was studied. His parents are cousins and both have decreased HRF20
      expression, suggesting that the deficiency is genetic. We established a cultured
      cell line (NCU1) which is HRF20 deficient from the patient's lymphocytes by
      Epstein-Barr-virus (EBV) infection. Northern blot analysis revealed HRF20 mRNA
      signals, indicating that HRF20 mRNA were transcribed. HRF20 cDNA was amplified by
      the polymerase chain reaction (PCR) method. Sequencing of the cDNA from the NCU1
      showed two single-base deletions at amino acid 16 and 96 from the N terminus of
      the mature protein. Deletion in the genomic DNA of peripheral blood lymphocytes
      was confirmed by the DNA sequence of an HRF20 open reading frame containing amino
      acid 16. Furthermore, the patient's parents and sister possessed both intact and
      deleted genomic HRF20 DNA while his brother's DNA was intact. These findings
      demonstrate that the HRF20 deficiency was genomic in origin, and that complete
      deletion was brought about by a homozygous abnormality in the HRF20 gene. The
      base deletion caused a codon frame shift resulting in failure to produce intact
      HRF20 protein in the patient.

PMID- 1382993
TI  - Modulation of integrin expression during mast cell differentiation.
AB  - Previously we have reported that rodent mast cells synthesize the mRNA encoding
      the alpha and beta integrin chains (alpha 4, beta 1 and beta 7) of the lymphocyte
      Peyer's patch adhesion molecule (LPAM)-1 and LPAM-2 lymphocyte homing receptors,
      and that they possess an alpha 4-containing integrin complex on their cell
      surface. In this report, we have examined the expression of these integrin chain
      genes by mature connective tissue mast cells (CTMC) and by bone marrow-derived
      mast cells (BMMC) differentiated from bone marrow precursor cells in the presence
      of interleukin (IL)-3 and/or the c-kit ligand (also known as mast cell growth
      factor and stem cell growth factor). High levels of both the beta 7 and beta 1
      transcripts were present in mature CTMC while those encoding the alpha 4 chain
      were absent. Similarly, when BMMC were grown in IL-3 for 28 days and analyzed for
      integrin chain transcripts, those specific for the alpha 4 chain were also
      diminished compared to beta 7 and beta 1 transcripts. To compare the expression
      of these integrin genes during mucosal mast cell and CTMC development, BMMC were
      derived in the presence of IL-3 alone, c-kit alone, or IL-3/c-kit together. These
      experiments indicated that c-kit inhibited the transcription of the beta 7 and Fc
      epsilon RI genes while enhancing alpha 4 transcript levels. The enhancement of
      alpha 4 levels, however, was abrogated with the addition of IL-3. Similarly, the
      c-kit-induced depression of beta 7 and Fc epsilon RI transcript levels was
      overcome by the addition of IL-3. These data suggest that the integrin complexes
      synthesized by the mast cells may differ depending upon their path of
      differentiation and that another alpha chain integrin may be synthesized to
      complex with the beta 7 and/or beta 1 chains.

PMID- 1382995
TI  - The influence of orientation and number of copies of T and B cell epitopes on the
      specificity and affinity of antibodies induced by chimeric peptides.
AB  - CBA and TO mice were immunized with chimeric peptide immunogens consisting of B
      cell (residues 404-414) and T cell (residues 288-302) epitopes from the F protein
      of measles virus. The chimeras were co-linearly synthesized to contain one or two
      copies of the T cell epitope linked to one or two copies of the B cell epitope
      via a glycine.glycine spacer. Two orientations were synthesized such that the T
      cell epitope(s) were located at either the amino or carboxyl terminus of the B
      cell epitope(s). The levels of antibody induced following immunization with the
      chimeras were assessed by enzyme-linked immunosorbent assay using microtiter
      plates coated with either the homologous chimera or the B cell epitope sequence.
      The affinities of the anti-chimera antibodies for the B cell epitope were
      assessed by a fluid-phase double-isotope radioimmunoassay. All the chimeras
      induced good antibody responses in both strains of mice with specificity for the
      B cell epitope. Chimeras containing two copies of the T cell epitope induced
      antibodies with higher affinity for the B cell epitope than did chimeras
      containing one copy of the T cell epitope or two copies of the B cell epitope.
      Furthermore, the amino terminal location of the T cell epitope in relation to the
      B cell epitope in the chimera induced higher affinity anti-B cell antibody than
      did the reverse orientation. These results suggest that orientation of epitopes
      and amino acid composition of chimeric peptides affect antigen processing and
      presentation to T cells which govern both the specificity and affinity of
      antibody produced. Thus, for the production of synthetic peptide immunogens with
      vaccine potential, attention needs to be given to the number and orientation of
      the component epitopes required to produce highest affinity antibody.

PMID- 1382996
TI  - CD44 can be activated to function as an hyaluronic acid receptor in normal murine
      T cells.
AB  - The hyaluronic acid (HA)-binding function of CD44 expressed on the cell surface
      of normal hematopoietic cells has been studied by assaying binding of
      fluoresceinated hyaluronic acid (F1-HA) and adhesion to immobilized HA. As has
      been observed previously, normal hematopoietic cells from bone marrow and spleen
      do not constitutively bind HA. A CD44-specific monoclonal antibody, IRAWB 14,
      which has been shown to rapidly induce HA binding in some CD44+ cell lines, was
      used to activate the HA-binding function of CD44 in these normal cells. Only
      splenic T cells were activated by the IRAWB 14 antibody to bind F1-HA. Upon
      activation, F1-HA binding correlated with the level of CD44 expression.
      Activation of HA binding allowed splenic T cells to adhere to HA immobilized on
      plastic and to an endothelial cell line in an HA-dependent manner. BALB/c and
      AKR/J splenic T cells differ in their level of CD44 expression, and this
      correlated with differences in their ability to bind HA upon antibody activation.
      The minor subpopulation of MEL-14- T cells were among the brightest F1-HA
      staining cells. We propose, on the basis of these and other results, that there
      are three states of CD44 function with respect to HA binding: (a) a non
      activatable, resting state, which cannot be rapidly activated to bind HA, as seen
      in most hematopoietic cells; (b) an activatable state, which can be rapidly
      converted to HA-binding function, in this case by the IRAWB 14 antibody,
      illustrated by T cells as shown here; and (c) a constitutively active state,
      which can bind HA without antibody activation, seen in some cell lines.

PMID- 1382997
TI  - Factors modifying survival pathways of germinal center B cells. Glucocorticoids
      and transforming growth factor-beta, but not cyclosporin A or anti-CD19, block
      surface immunoglobulin-mediated rescue from apoptosis.
AB  - The tendency for germinal center (GC) B cells to enter apoptosis is suppressed on
      engaging antigen receptor with immobilized anti-immunoglobulin; cross-linking of
      surface CD40 by monoclonal antibodies provides an additional signal for rescuing
      GC cells from programmed death. These observations are believed to reflect events
      that, in vivo, would allow for the selection of centrocytes which have undergone
      somatic mutation on Ig V-region genes to generate antigen receptor of high
      affinity. The purpose of the present study was to identify factors capable of
      modifying the survival pathways of GC cells. Transforming growth factor-beta, at
      an optimal concentration of 1 ng/ml, was found to inhibit surface immunoglobulin
      (sIg)-mediated rescue of GC cells but had no influence on survival promoted
      through CD40. Both routes of rescue were blocked by the glucocorticoid
      prednisolone at pharmacological concentrations (ID50 = 10(-7) M). Cyclosporin A,
      an antagonist of sIg-mediated signaling in resting B cells, failed to block
      rescue of GC cells through either of the receptor-activated pathways. Antibody to
      CD19--which also suppresses the activation of resting B cells--not only left GC
      cell rescue undiminished, but rather provided a modest survival signal of its
      own; interferon-alpha behaved similarly while interferon-gamma failed to
      influence GC cell survival in either direction.

PMID- 1382998
TI  - Competitive inhibition by NBQX of kainate/AMPA receptor currents and excitatory
      synaptic potentials: importance of 6-nitro substitution.
AB  - We evaluated the inhibitory potencies at excitatory amino acid receptors of 2,3
      dihydroxy-7-sulfamoyl-benzo[f]quinoxaline (BQX) and its 6-nitro derivative, NBQX.
      Currents activated by kainate or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) in two-electrode voltage-clamp recordings of Xenopus
      oocytes injected with rat cortex mRNA were inhibited by BQX and NBQX: the
      apparent Ki values versus kainate were 14 microM and 78 nM, respectively, and
      versus AMPA were 23 microM and 63 nM, respectively. Thus, to a degree even more
      marked than with other quinoxalinedione derivatives, 6-nitro substitution of BQX
      to yield NBQX increases potency (200-fold) at the non-NMDA ionotropic receptor,
      but does not confer selectivity for kainate or AMPA. Schild analysis of the NBQX
      inhibition of the kainate and AMPA currents yielded pA2 values of 7.17 +/- 0.05
      and 7.05 +/- 0.10, respectively, and slopes near unity confirming the competitive
      nature of the inhibition. Neither BQX nor NBQX significantly inhibited the
      current activated by glycine plus NMDA. The selectivity ratio of NBQX (greater
      than 5000-fold) is by far the greatest of any quinoxalinedione derivative
      antagonist of the kainate/AMPA receptor. BQX and NBQX also inhibited the
      excitatory postsynaptic field potentials mediated by kainate/AMPA receptors in
      the CA1 region of hippocampal slices after stimulation of the Schaffer collateral
      commissural pathways with IC50 values of 130 and 0.90 microM, respectively. The
      10-fold differences between the IC50 values in hippocampal slices and the Ki
      values in Xenopus oocytes correlate closely with data for other quinoxalinedione
      derivative antagonists.

PMID- 1382999
TI  - K+ channel activator inhibition of neurogenic goblet cell secretion in guinea pig
      trachea.
AB  - A potassium (K+) channel activator, BRL 38227, inhibited goblet cell secretion in
      guinea-pig trachea induced by either electrical stimulation of the vagus nerves
      or acute inhalation of cigarette smoke, two stimuli which activate both
      cholinergic nerves and capsaicin-sensitive sensory nerves. BRL 38227 failed to
      inhibit methacholine- or substance P-induced goblet cell secretion which suggests
      that K+ channel activators inhibit neurogenic goblet cell secretion via a
      prejunctional effect on cholinergic and sensory nerves.

PMID- 1383000
TI  - Nucleotide receptors on DDT1 MF-2 vas deferens cells.
AB  - On exposure to triphosphatic nucleotides vas deferens DDT1 MF-2 smooth muscle
      cells responded with an outward K+ current as measured with the whole-cell patch
      clamp configuration. The rank order of potency was: ATP greater than UTP greater
      than TTP greater than CTP = GTP. The responses evoked by these agonists were
      blocked by suramin. Adenosine, ADP, alpha, beta-methylene-ATP and 2-methylthio
      ATP did not affect the transmembrane current. The responses evoked by the
      nucleotides in DDT1 MF-2 cells are supposed to be mediated via 'nucleotide'
      receptors.

PMID- 1383001
TI  - Dopamine receptor agonists and antagonists enhance ATP-activated currents.
AB  - The effects of dopamine and related compounds on ATP-activated channels were
      investigated in pheochromocytoma PC12 cells. Dopamine (10 microM) enhanced an
      inward current activated by 100 microM ATP. A similar enhancement of the ATP
      activated current was observed with apomorphine (10 microM), a non-selective
      dopamine receptor agonist, with (+)-SKF-38393 (10 microM), a selective dopamine
      D1 receptor agonist, and with (-)-quinpirole (10 microM), a selective dopamine D2
      receptor agonist. Moreover, (+)-SCH-23390 (30 microM), a dopamine D1 receptor
      antagonist, and (-)-sulpiride (30 microM), a dopamine D2 receptor antagonist,
      also enhanced the ATP-activated current. The results suggest that ATP-activated
      channels are modulated by dopaminergic mechanisms, and that this modulation
      cannot be attributed to any single class of dopamine receptors.

PMID- 1383002
TI  - Capsazepine as a selective antagonist of capsaicin-induced activation of C-fibres
      in guinea-pig bronchi.
AB  - We investigated the action of capsazepine, an antagonist of the actions of
      capsaicin on sensory neurones, on the contractile responses evoked by capsaicin
      or by electrical field stimulation (EFS) in guinea-pig bronchi. Capsazepine (10(
      5) M) selectively inhibited responses to capsaicin, producing a significant
      change in EC50 values but not the Hill coefficient (nH), suggesting that
      capsazepine acts as a competitive antagonist (apparent pKB = 5.12) whereas
      ruthenium red is a non-competitive antagonist. Capsazepine and ruthenium red were
      without effect on EFS-induced responses.

PMID- 1383003
TI  - The metabotropic excitatory amino acid receptor agonist 1S,3R-ACPD selectively
      potentiates N-methyl-D-aspartate-induced brain injury.
AB  - The role of metabotropic type excitatory amino acid receptors in brain injury was
      assessed using the selective metabotropic receptor agonist, (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD). Intrastriatal stereotaxic
      injection of 1S,3R-ACPD (250 nmol) in PND 7 rats produced little brain injury as
      assessed by hemispheric weight disparities. However, 1S,3R-ACPD markedly
      potentiated N-methyl-D-aspartate (NMDA)-, but not alpha-amino-3-hydroxy-5-methyl
      4-isoxazoleproprionic acid (AMPA)-, mediated brain injury. This effect was
      stereoselective since the inactive metabotropic agonist, 1R,3S-ACPD, did not
      potentiate NMDA toxicity.

PMID- 1383004
TI  - Effects of the tripeptide substance P antagonist, FR113680, on airway
      constriction and airway edema induced by neurokinins in guinea-pigs.
AB  - FR113680 is a newly developed tripeptide substance P (SP) receptor antagonist.
      The effects of FR113680 on airway constriction and airway edema induced by
      neurokinins were investigated in guinea-pigs. In in vitro experiments, FR113680
      inhibited the contraction of isolated guinea-pig trachea induced by SP and
      neurokinin A (NKA) in a dose-dependent manner with IC50 values of 2.3 x 10(-6)
      and 1.5 x 10(-5) M, respectively. The tracheal contraction induced by histamine
      and acetylcholine was not affected by FR113680. FR113680 (5 x 10(-5) M) also
      significantly inhibited the atropine-resistant contraction of isolated guinea-pig
      bronchi induced by electrical field stimulation. In in vivo experiments, FR113680
      given i.v. inhibited SP-induced airway constriction in guinea-pigs at doses of 1
      and 10 mg kg-1. However, FR113680 only inhibited NKA- and capsaicin-induced
      airway constriction by 40-50% even at a dose of 10 mg kg-1. FR113680 also
      inhibited SP-induced airway edema in guinea-pigs with the same potency as it
      inhibited SP-induced airway constriction. Histamine-induced airway constriction
      and airway edema were not affected at a dose of 10 mg kg-1. These results suggest
      that FR113680 preferentially inhibits responses induced by NK1 receptor
      activation (SP-induced airway constriction and airway edema), but is less
      effective on a NK2 receptor-induced response (airway constriction by NKA and
      neurogenic stimulation).

PMID- 1383005
TI  - Inhibitory actions of prostaglandin E1 on neurogenic plasma extravasation in rat
      airways.
AB  - To determine whether neurogenic inflammation can be inhibited by prostaglandin E1
      (PGE1), that is suggested to have an inhibitory effect on neuropeptide release
      from airway sensory nerves, we examined plasma extravasation in the airways of
      anesthetized rats in vivo with Evans blue due as a marker. Neurogenic
      inflammation was produced by an i.v. injection of capsaicin (100 micrograms/kg)
      or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V
      for 1 min). Capsaicin injection significantly increased leakage of dye in the
      trachea and main bronchi. Similar increases in leakage were seen in the trachea
      and right bronchus on electrical stimulation of the right vagus nerve. PGE1 (1
      1000 micrograms/kg) inhibited the leakage induced by capsaicin in the trachea and
      bronchi concentration dependently with complete inhibition at a concentration of
      1000 micrograms/kg. Likewise, PGE1 (1000 micrograms/kg) significantly inhibited
      electrical stimulation-induced leakage in the trachea and right bronchus (P less
      than 0.01). I.v. substance P (SP; 1 microgram/kg) increased Evans blue dye
      extravasation in the same way as the leakage induced by capsaicin and electrical
      stimulation but PGE1 (1000 micrograms/kg) failed to inhibit SP-induced leakage in
      the trachea and main bronchi (P greater than 0.20). These results suggest that
      PGE1 inhibits neurogenic plasma leakage by presynaptic inhibition of the release
      of neuropeptides from sensory nerves.

PMID- 1383007
TI  - Interaction of domoic acid and several derivatives with kainic acid and AMPA
      binding sites in rat brain.
AB  - We have determined the inhibitory potencies of domoic acid and a series of
      derivatives of domoic acid at kainic acid and alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) binding sites in rat forebrain membranes. These
      derivatives of domoic acid differed in the configuration, stereochemistry, and
      degree of saturation of the side chain attached to C-4 of the prolyl ring. The
      binding data were analyzed in terms of one or two classes of sites as
      appropriate. Domoic acid and kainic acid displayed similar inhibition constants
      at [3H]kainic acid sites (IC50 = 5 and 7 nM, respectively). At both kainic acid
      and AMPA binding sites, all of the compounds tested were less potent than domoic
      acid itself. At high affinity [3H]kainic acid sites, the derivatives could be
      categorized into two groups; those with nanomolar affinity and those with
      micromolar affinity. All members of the former group possessed a side chain with
      the first double bond intact and in the Z (cis) configuration. The more distal
      atoms present in the extended side chain of domoic acid did not appear to
      contribute to the high affinity interaction with the kainic acid receptor.
      Although all the compounds tested were weaker inhibitors of [3H]AMPA binding
      compared to [3H]kainic acid binding, there was a high correlation between the
      rank order of potency of the seven domoic acid derivatives at [3H]kainic acid and
      at [3H]AMPA binding sites. The inhibition data for kainic acid at [3H]AMPA
      binding sites were described adequately in terms of a 1-site model, whereas the
      data for domoic acid required two classes of sites.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1383008
TI  - Pain and inflammation evoked in human skin by bradykinin receptor antagonists.
AB  - We showed the intrinsic effects of the bradykinin (BK) receptor antagonists, NPC
      567 (D-Arg-[Hyp3,D-Phe7]BK) and NPC 349 (D-Arg-[Hyp3,Thi5,8,D-Phe-7]BK), in the
      skin of humans. NPC 567 and NPC 349 caused dose-dependent pain, wheal, and flare
      on intracutaneous injection. After bradykinin, only the pain, but not the wheal
      and flare reactions were dose-dependent. The intravenous application of
      antihistamines (dimetidinmaleate and ranitidine) had little effect on pain
      intensity and reduced both wheal and flare response to the antagonists but not to
      bradykinin. We conclude that NPC 567 and NPC 349 have pain-evoking and histamine
      releasing properties in the skin of humans which may limit their therapeutic and
      experimental use.

PMID- 1383006
TI  - The effect of adrenergic drugs on serotonin metabolism in the nucleus raphe
      dorsalis of the rat, studied by in vivo voltammetry.
AB  - The serotonin (5-HT) and norepinephrine (NE) system participate in the control of
      behavioural functions. The experiments were aimed at the question whether the NE
      system of the locus coeruleus interferes with the 5-HT activity of the nucleus
      raphe dorsalis and of which receptors are possibly involved. The alpha 1- and
      beta-adrenoceptor agonists methoxamine and isoproterenol, as well as a high dose
      (600 micrograms/kg i.p.) of the alpha 2-adrenoceptor agonist clonidine, increased
      extraneuronal 5-hydroxyindoleacetic acid (5-HIAA) levels in the nucleus raphe
      dorsalis as measured by in vivo voltammetry. In contrast, a low dose (60
      micrograms/kg i.p.) of clonidine and the alpha 1-, alpha 2- and beta-adrenoceptor
      antagonists, prazosin, piperoxane, and atenolol, reduced the 5-HIAA
      concentration. In the locus coeruleus, the origin of NE projections to the
      nucleus raphe dorsalis, clonidine decreased whereas piperoxane enhanced
      extracellular 3,4-dihydroxyphenylacetic acid (DOPAC), an index of NE metabolism
      in the locus coeruleus. The results suggest that 5-HT neurotransmission in the
      nucleus raphe dorsalis is stimulated by the NE system of the locus coeruleus and
      that adrenoceptor drugs may affect 5-HT neuronal activity in addition to NE
      neurotransmission.

PMID- 1383009
TI  - Mechanisms of propofol action on ion currents in the myelinated axon of Xenopus
      laevis.
AB  - The effect of the intravenous anaesthetic, propofol (2,6-diisopropylphenol), was
      investigated on frog myelinated axons under voltage-clamp conditions. The effect,
      in the concentration range 60 microM to 10 mM, was a combination of (i) a
      negative shift of the steady state activation and inactivation curves for both
      Na+ and K+ currents (INa,IK), (ii) a voltage-independent block of INa, but not of
      IK, and (iii) a slowed time course of IK activation. The shift was dose-dependent
      and, at 1 mM, about -10 mV for the activation and -16 mV for the inactivation
      curves. The voltage-independent INa block showed 1:1 stoichiometry and 50%
      reduction at 2.7 mM. The slowed IK activation showed saturation at 1 mM with a
      doubled time to half steady state value. All the effects were only partially
      reversible and showed a complex time course at application and washing. The shift
      of potential dependence may be explained by a general effect on the membrane
      electric field. The findings suggest effects directly on channel proteins as well
      as on membrane lipids.

PMID- 1383010
TI  - The effect of Ca2+ channel modulators on vagally induced bronchoconstriction in
      the guinea-pig.
AB  - The effects of N- and L-type voltage operated calcium channel (VOCC) antagonists
      were examined on the bronchoconstriction induced by vagal stimulation in
      artificially respired guinea-pigs. Vagal stimulation produced a reproducible and
      consistent bronchoconstrictor response which corresponded to an increase in
      pulmonary inflation pressure equivalent to (10.4 +/- 1.0%) of the maximum. This
      vagally induced rise in pulmonary inflation pressure was reduced (54% P less than
      0.001) by pretreatment with atropine (1 mg/kg i.v.) and almost completely blocked
      by pretreatment with capsaicin (54.5 mg/kg s.c.) and atropine. omega-Conotoxin
      GVIA (CgTx) (5-20 micrograms/kg i.v.) caused a dose and time-related inhibition
      of the vagal response but did not affect either methacholine or substance P (SP)
      induced bronchoconstriction. Combination studies with CgTx, atropine and
      capsaicin pretreatment revealed that CgTx effectively blocked both the atropine
      sensitive cholinergic component and the capsaicin-sensitive non-adrenergic non
      cholinergic (NANC) component of the vagal response. Selective L-type VOCC
      antagonists nicardipine, diltiazem and verapamil, at doses which had significant
      cardiovascular effects, did not reduce the rise in pulmonary inflation pressure
      to vagal stimulation. This study indicates that N-type VOCCs are important in
      controlling the release of neurotransmitters from both the cholinergic and NANC
      neurones within the airways of guinea-pigs.

PMID- 1383011
TI  - Magainin 2, a natural antibiotic from frog skin, forms ion channels in lipid
      bilayer membranes.
AB  - We have examined the ion channel forming properties of magainin 2 by
      incorporating the peptide into artificial lipid bilayers held under voltage
      clamp. Magainin 2 increased lipid bilayer conductance in a concentration
      dependent manner with a Hill coefficient of 1.7. The magainin 2 conductance was
      selective for monovalent cations over anions with a ratio of 5:1 and had both
      voltage-sensitive and -insensitive components. Two structurally related but
      antibiotically less potent analogues, magainin 1 and Z-12, also increased lipid
      bilayer conductance with a similar ion selectivity but these peptides were less
      potent than magainin 2. We propose that the weak cation selectivity of the
      magainin channels can be accounted for by the inclusion of negatively charged
      lipids in the channel complex and suggest two possible structures for such a
      channel. The ionophoric properties of these peptides are likely to be proximal to
      their antibiotic activities.

PMID- 1383012
TI  - Effects of N-ethyl,N-nitrosourea on monoamine concentrations and metabolizing
      enzymes in mouse brain regions.
AB  - N-ethyl,N-nitrosourea is a well known alkylating agent and produces central
      nervous system-specific tumors in several laboratory animal species. In the
      present study, young male CD-1 mice were treated by i.p. injections of 0, 2, 8,
      or 32 mg/kg body weight N-ethyl,N-nitrosourea, twice a week for 3 weeks.
      Endogenous levels of brain monoamine neurotransmitters and their selected
      metabolites; norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT),
      vanillylmandelic acid (VMA), dihydroxyphenyl acetic acid (dopac), homovanillic
      acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and dihydroxyphenylalanine
      (dopa) were measured using HPLC with electrochemical detection. N-ethyl,N
      nitrosourea treatment caused an increase of NE and 5-HT in the hypothalamus and
      striatum. Increased levels of 5-HIAA were noticed in the same brain regions.
      Elevated levels of NE were also observed in the cerebral cortex, medulla
      oblongata and the cerebellum. The major metabolite of NE, VMA, was decreased in
      several brain regions to non-detectable levels. Histopathological examination of
      brain tissue did not reveal any pathologic lesions. The increases in brain amines
      were associated with increased activity of tryptophan hydroxylase in the
      hypothalamus and corpus striatum. Dopa-decarboxylase was elevated in the cerebral
      cortex at a low dose of N-ethyl,N-nitrosourea only, whereas the monoamine oxidase
      activity was unaltered. Results indicated that N-ethyl,N-nitrosourea exposure may
      cause an elevation of steady state levels of various biogenic amines in brain
      areas and these changes to some extent are consistent with the altered activity
      of metabolizing enzymes.

PMID- 1383013
TI  - Vitronectin is the major serum protein essential for NGF-mediated neurite
      outgrowth from PC12 cells.
AB  - The rat pheochromocytoma cell line PC12 can be induced to differentiate in
      response to nerve growth factor (NGF) in the presence of 1% fetal calf serum
      (FCS). Using a novel assay procedure we have developed a purification protocol
      which has allowed the isolation of the protein in serum responsible for neurite
      outgrowth after NGF treatment. FCS has been fractionated using four
      chromatographic procedures and in each case the peak of biological activity
      copurified with vitronectin. We have concluded, therefore, that vitronectin is
      the protein present in FCS which can mediate NGF-dependent neurite outgrowth in
      PC12 cells. Vitronectin and fibronectin from FCS have been chromatographically
      separated and only the former is capable of inducing neurite outgrowth. We have
      also shown that vitronectin utilizes the RGD amino acid sequence in binding to
      the surface of PC12s.

PMID- 1383014
TI  - Effect of recombinant IGF binding protein-1 on primary cultures of human
      keratinocytes and fibroblasts: selective enhancement of IGF-1 but not IGF-2
      induced cell proliferation.
AB  - The present report describes the mitogenic effect of recombinant IGF-2 on
      cultured human keratinocytes and fibroblasts compared to that of IGF-1.
      Furthermore, the modulating effect of a recently expressed recombinant form of
      placental-derived IGF-binding protein 1 (IGFBP-1) on IGF-induced proliferation
      was examined. A dose-dependent increase, up to 100%, in cell proliferation was
      seen in cultured human keratinocytes with IGF-2 and -1 and the proliferative
      response was comparable to the effect of epidermal growth factor (EGF). In human
      fibroblasts, IGF-1 stimulated DNA synthesis up to 300% for IGF-1 and up to 200%
      for IGF-2. The mitogenic effect of IGF-1 was enhanced by IGFBP-1 in both cell
      types. In contrast, the IGF-2-induced mitogenic effect was unperturbed. These
      findings indicate that the interaction between IGFs and their binding proteins
      may induce different responses depending upon the ligand and the target cell.

PMID- 1383015
TI  - Regulation of adherens junction protein expression in growth-activated 3T3 cells
      and in regenerating liver.
AB  - The expression of the adherens junction proteins vinculin, alpha-actinin, and
      talin was compared in serum-stimulated 3T3 cells and in regenerating rat liver
      following partial hepatectomy. The levels of vinculin RNA and protein synthesis
      were rapidly and transiently elevated in growth-activated fibroblasts (peaking at
      2-3 h) and in regenerating liver (at 4-8 h), preceding the replicative stage.
      alpha-Actinin expression was also induced, but more slowly (peaking at 6-8 h in
      3T3 cells and at 28 h in regenerating liver), and remained elevated when DNA
      synthesis was proceeding in both systems. The expression of talin RNA was only
      slightly elevated in 3T3 cells following serum stimulation, and it remained
      largely unchanged in regenerating liver. The levels of RNA coding for fibronectin
      and for the beta 1-integrin subunit were transiently and extensively induced
      during liver regeneration (fibronectin with a peak at 8 h and beta 1-integrin at
      12 h). The uvomorulin RNA level, and the expression of the liver-specific genes
      albumin and transthyretin, decreased in regenerating liver. The results suggest a
      physiologically significant regulation in the expression of structural components
      which link the extracellular matrix to the microfilament system in growth
      activated fibroblasts and in regenerating liver.

PMID- 1383016
TI  - The thermoresistant state: protection from initial damage or better repair?
AB  - The induction of and recovery from heat-induced perturbations in several cellular
      parameters were examined in normal, transiently thermotolerant, and permanently
      heat-resistant HA-1 Chinese hamster fibroblasts. The initial heat-induced
      perturbations in total cellular protein synthesis, RNA synthesis, vimentin
      containing intermediate filaments, and nuclear protein mass were similar in the
      three different cell types which display various levels of thermal resistance as
      determined by clonogenic survival. The posthyperthermia recovery from the heat
      induced perturbations in all of the cellular parameters was more rapid in both
      the permanently heat-resistant cells and in the transiently thermotolerant cells.
      This response was observed in cells in which transient thermotolerance was
      induced by either a mild heat shock or exposure to sodium arsenite. The
      development and decay of the capacity for more rapid recovery from the initial
      heat-induced perturbations in total cellular protein and RNA synthesis paralleled
      the development and decay of clonogenic thermotolerance. Overall, these results
      support the notion that more rapid recovery from similar levels of heat-induced
      perturbations in various cellular parameters are a salient feature of both the
      transiently and permanently heat-resistant state.

PMID- 1383017
TI  - Specific transcellular staining of microglia in the adult rat after traumatic
      degeneration of carbocyanine-filled retinal ganglion cells.
AB  - The present work was undertaken to assess the fate of ganglion cell debris in the
      axotomized retina of adult rats and employed a new technique to label
      phagocytosing microglia via the internalized material. In the main experiment,
      transection axotomy was performed on the intraorbital segment of the optic nerve,
      and a fast-transported, vital fluorescent styryl dye (4Di-10ASP) was deposited at
      the ocular stump of the nerve in order to pre-label retrogradely the ganglion
      cells destined to die because of the axotomy. Optic nerve transection resulted in
      progressive degradation of ganglion cell axons, perikarya, and dendrites within
      the retina and in release of fluorescent material, which was then incorporated
      into cells identified as microglia. No other retinal cells stained, although
      astrocytes and Muller's cells also responded to neuron degeneration by
      accumulating glial fibrillary acidic protein. Incorporation of labelled material
      into microglia topo-chronologically paralleled the ganglion cell degeneration
      starting within the optic fibre layer (OFL) and proceeding towards the ganglion
      cell layer (GCL) and the inner plexiform layer (IPL) of the affected retina. Long
      term labelling of microglia monitored up to 3 months after optic nerve
      transection indicated that labelled microglial cells persisted within the retina.
      Microglia displayed a strong territorial arrangement within the GCL and IPL, and
      staggered, bilaminated distribution in both layers. These studies directly prove
      that microglia in the retina can be transcellularly labelled during traumatic
      degeneration of ganglion cells. The findings suggest that microglial cells play
      an important role in axotomy-induced wound healing and removal of cell debris.

PMID- 1383018
TI  - Divalent cation effects on lens conductance and stretch-activated cation
      channels.
AB  - In patch clamp studies of apical membrane from frog lens epithelium, the most
      frequently observed channel is 'stretch-activated', highly selective for cations
      over anions but showing little selectivity for Na+ vs. K+. In normal
      physiological saline, the open channel conductance is 25-30 pS and quite linear
      over +/- 100 mV. In the absence of extracellular divalent ions, the open channel
      conductance for inward current flow increases to about 50 pS at the normal lens
      resting voltage of -75 mV, whereas the conductance for outward current flow is
      unaffected. In the intact lens, removal of extracellular divalents causes the
      input conductance approximately to double and the intracellular voltage to
      depolarize from -74 to -58 mV. A variety of divalent ions block this change in
      whole lens conductance and voltage in the same order in which they block the
      'stretch channels'. Single voltage-clamped epithelial cells also increase their
      conductance when Ca2+ is removed from their bathing medium. There are, therefore,
      some striking parallels between the open channel properties of the 'stretch
      activated' cation channel and the response of the whole lens or single lens cells
      to removal of extracellular Ca2+. There are also inconsistencies. This channel is
      apparently not open in the normal resting lens so removal of extracellular Ca2+
      must cause it to open if it is indeed responsible for the increase in lens
      conductance. However, we have not been able to demonstrate convincingly an
      increase in open probability at the single-channel level when external divalents
      are removed.

PMID- 1383019
TI  - Inhibition of corneal neovascularization in the rat by SK&F 86002, a dual
      inhibitor of arachidonic acid metabolism.

PMID- 1383020
TI  - Immunohistochemistry and neurochemistry of the habenulo-interpeduncular
      connection after partial developmental depletion of habenular cholinergic neurons
      in the rat.
AB  - The habenulo-interpeduncular system of the rat constitutes an interesting model
      to address quantitatively problems related to synaptogenesis and to the
      interactions between neuronal populations after selective alteration of these
      elements during development. In the present study this has been achieved by
      experimentally reducing, through gestational treatment with methylazoxymethanol
      acetate (MAM), the population of cholinergic neurons of the medial habenula which
      projects to the interpeduncular nucleus. Immunohistochemical analysis gave
      evidence that the topographical localization of the cholinergic and the substance
      P-containing populations in the medial habenula was not altered by MAM treatment.
      Furthermore, the topographical distribution of cholinergic fibers and terminals
      in the interpeduncular nucleus, which reflects the habenulo-interpeduncular
      projection as well as cholinergic projections coming from different sources, was
      substantially preserved. The same was also true concerning the terminal
      distribution of substance P in the interpeduncular nucleus. Quantitative
      radioassays demonstrated a sizable decrease of overall ChAT activity in both the
      habenulae and the interpeduncular nucleus. By comparison of 1 month-old and 3
      month-old animals it appeared that this effect was partially reversed with age in
      the interpeduncular nucleus.

PMID- 1383023
TI  - Are stretch-sensitive channels in molluscan cells and elsewhere physiological
      mechanotransducers?
AB  - Single-channel recordings of dozens of cell types, including invertebrate
      (molluscan) and vertebrate heart cells, reveal stretch-sensitive ion channels.
      The physiological roles of these channels are undoubtedly diverse but it is
      usually assumed that the roles they play are related to the channels'
      mechanosensitive gating. Whether this assumption is valid remains to be seen.
      Attempts to connect the single-channel observations with the mechanical aspects
      of physiological or developmental processes are discussed. In the case of
      molluscan cells, recent work suggests that their stretch channels have
      physiological functions unrelated to mechanosensitive gating.

PMID- 1383021
TI  - Emergence of callosally projecting neurons with stellate morphology in the visual
      cortex of the kitten.
AB  - Callosally projecting neurons in areas 17 and 18 of the adult cat can be
      classified into two types on the basis of their dendritic morphology: pyramidal
      and stellate cells. The latter are nearly exclusively of the spinous type and are
      predominantly located in upper layer IV. Retrograde transport of the carbocyanine
      dye DiI, applied to the corpus callosum, showed that, up to P6, all callosally
      projecting neurons resemble pyramids in the possession of an apical dendrite
      reaching layer I. At P10, however, callosally projecting neurons with stellate
      morphology were found. A study was designed to distinguish whether these neurons
      are late in extending their axons to the corpus callosum or, alternatively, have
      transient apical dendrites. To this end, callosally projecting neurons were
      retrogradely labeled by fluorescent beads injected in areas 17 and 18 at P1-P3
      and then either relabeled with DiI applied to the corpus callosum at P10 or
      intracellularly injected with Lucifer Yellow at P57. Double-labeled stellate and
      pyramidal cells were found in similar proportions to those found for the total,
      single-labeled population of callosally projecting neurons. It is therefore
      concluded that callosally projecting spiny stellate cells initially possess an
      apical dendrite and a pyramidal morphology. At P6, i.e. close to the time when
      stellate cells appear, layer IV neurons with an atrophic apical dendrite were
      found, suggestive of an apical dendrite in the process of being eliminated.

PMID- 1383024
TI  - Keratinophilic fungi isolated from soil of Italian parks in the province of
      Pavia.
AB  - Soil samples collected from 9 parks in the Italian province of Pavia were baited
      with hair and feathers for the isolation of keratinophilic fungi. The dominant
      species were the teleomorphs Arthroderma gypsea, A. uncinatum, Ctenomyces
      serratus and Aphanoascus fulvescens with their anamorphs. Among the other species
      isolated, Amauroascus mutatus, Gymnascella dankaliensis, Gymnoascus intermedius
      and Gymnoascus reessii were recorded. The distribution of these fungi is
      discussed and related to previous records.

PMID- 1383022
TI  - A review of the electrophysiological, pharmacological and single channel
      properties of heart ventricle muscle cells in the snail Lymnaea stagnalis.
AB  - Although a considerable body of information has accumulated describing the
      pharmacological properties of a wide range of molluscan muscle types, the
      physiological bases underlying these properties have not been thoroughly
      investigated. At present, little is known about the types of ion channels and
      their regulation in molluscan muscle cell membranes. Voltage-clamp, and more
      recently, patch-clamp techniques have revealed molluscan muscles possess a
      complex array of channel types with various pharmacological and
      electrophysiological properties. The gating properties of these channels and
      their modulation by chemical agents, however, are still poorly understood. This
      review summarizes some aspects of molluscan muscle function with particular
      reference to the heart ventricle muscle of the pond snail, Lymnaea stagnalis.

PMID- 1383025
TI  - Identification of antigens reacting with anti-Candida albicans germ tube
      antibodies.
AB  - Anti-Candida albicans germ tube antibodies can be induced in rabbits immunized
      with different C. albicans extracts. Antigens responsible for the induction of
      those antibodies have molecular weights of approximately 230-250, 62, 43 and 41
      kDa. These antigens are present in the cell wall of both C. albicans
      morphological forms, although their location seems to be different.

PMID- 1383027
TI  - Developmental expression of voltage-sensitive K+ channels in mouse skeletal
      muscle and C2C12 cells.
AB  - The developmental expression of voltage-sensitive K+ channels was analyzed by
      Northern blot in mouse skeletal muscle. Of nine Shaker-like genes studied, eight
      are expressed in this mammalian muscle. Their expression is differentially
      regulated during development. The mouse cell line C2C12 has been used to study
      expression of voltage-sensitive K+ channels during in vitro myotube
      differentiation. Different voltage-sensitive K+ channel messages are also
      expressed in these cells which display a pattern of expression depending upon the
      differentiation stage. The message for the very peculiar K+ channel of IsK type
      could only be detected by polymerase chain reaction on skeletal muscle mRNA.

PMID- 1383028
TI  - Cloning and sequencing of mouse collagenase cDNA. Divergence of mouse and rat
      collagenases from the other mammalian collagenases.
AB  - Mouse collagenase cDNA was cloned and sequenced. The deduced amino acid sequence
      was compared to those of the other mammalian collagenases and related matrix
      metalloproteinases. These comparisons, as well as those of some enzymatic
      properties, show that the rodent (mouse and rat) interstitial collagenases are
      very similar but differ more from the other interstitial collagenases than does
      human neutrophil collagenase. This supports the hypothesis that the order
      Rodentia is an outgroup to the other eutherian (placental) mammalian orders.

PMID- 1383029
TI  - Glycopeptide of P0 protein inhibits homophilic cell adhesion: competition assay
      with transformants and peptides.

PMID- 1383026
TI  - Cytological immunodetection of yeast glycoprotein secretion.
AB  - Expression of antigenic epitopes shared by secreted yeast glycoproteins was
      studied using specific immunological probes. Application of cytological and
      ultrastructural methods of immunodetection, employing monoclonal antibodies,
      permitted us to localize these glycoproteins in the cytoplasm, through the cell
      wall and at the yeast cell surface. Importance of glycosylation-secretion
      relationships were evaluated in the secretion process of these molecules. The
      cell wall crossing and the cell surface distribution of antigenic glycoproteins
      was described in immunoelectron microscopy and immunofluorescence. Some
      preferential secretion "ways" were suspected through the yeast cell wall leading
      to an heterogenous distribution of cell surface glycoproteins destined to be
      excreted into the medium. Antigenic variability of cell wall glycoproteins
      expression was discussed in relation with the glycoprotein secretion.

PMID- 1383030
TI  - A new intrinsic fluorescent probe for proteins. Biosynthetic incorporation of 5
      hydroxytryptophan into oncomodulin.
AB  - The tryptophan analog, 5-hydroxytryptophan (5HW), has a significant absorbance
      between 310-320 nm, which allows it to act as an exclusive fluorescence probe in
      protein mixtures containing a large number of tryptophan residues. Here for the
      first time a method is reported for the biosynthetic incorporation of 5HW into an
      expressed protein, the Y57W mutant of the Ca2+ binding protein, oncomodulin.
      Fluorescence anisotropy and time-resolved fluorescence decay measurements of the
      interaction between anti-oncomodulin antibodies and the 5HW-incorporated
      oncomodulin conveniently provide evidence of complex formation and epitope
      identification that could not be obtained with the natural amino acid. This
      report demonstrates the significant potential for the use of 5HW as an intrinsic
      probe in the study of structure and dynamics of protein-protein interactions.

PMID- 1383031
TI  - Glycopeptide of P0 protein inhibits homophilic cell adhesion: competition assay
      with transformants and peptides.

PMID- 1383032
TI  - Processing of hepatocyte growth factor to the heterodimeric form is required for
      biological activity.
AB  - Hepatocyte growth factor is a plasminogen-like molecule with diverse biological
      effects. Although it is synthesized as a single chain polypeptide, it was
      originally purified as a disulfide-linked heterodimer which was generated by an
      internal proteolytic event. Subsequent work indicated that preparations
      consisting largely of the monomeric form also exhibited potent activity. By using
      a combination of protease inhibition and site-directed mutagenesis, we
      established that conversion of the single chain polypeptide to the heterodimer
      occurred during the bioassay and was required for mitogenic and motogenic
      activity.

PMID- 1383033
TI  - Effect of modulation of protein kinase C on the cAMP-dependent chloride
      conductance in T84 cells.
AB  - The regulation of chloride conductance was investigated in the T84 human colon
      carcinoma cell line by the quenching of the fluorescent probe 6-methoxy-N-(3
      sulfopropyl)quinolinium. The permeable cAMP analog 8-Br-cAMP (100 microM) and the
      calcium ionophore ionomycin (1 microM) activate a chloride conductance. A
      prolonged (4 h) preincubation of cells with phorbol 12-myristate 13-acetate (100
      nM) or with the diacylglycerol analog 1-oleoyl-2-acetyl-glycerol (100 microM):
      (i) down-modulates to almost zero the protein kinase C activity in the membranes;
      (ii) inhibits the activation of the chloride conductance mediated by 8-Br-cAMP
      but not by calcium; (iii) reduces the mRNA without changing the expression of the
      protein product of the cystic fibrosis gene. The data suggest that PKC is
      essential for the activation of the cAMP-dependent chloride conductance in T84
      cells.

PMID- 1383034
TI  - Proto-oncogene c-jun and c-fos messenger RNAs increase in the liver of carnitine
      deficient juvenile visceral steatosis (jvs) mice.
AB  - We determined the mRNA levels of c-jun and c-fos in the liver of C3H-H-2 degrees
      jvs mice. Both were higher in jvs mice than in normal mice. The level of c-jun
      mRNA increased gradually after birth, but in the control mice there was almost no
      change. In addition, alpha-fetoprotein and aldolase A mRNA levels were also
      higher than in normal littermates. These results suggest that the pattern of the
      gene expression in jvs mice partly resembles the one that occurs in
      undifferentiated hepatocytes and/or hepatocellular carcinoma.

PMID- 1383035
TI  - Retinoic acid-induced changes in differentiation-defective embryonal carcinoma
      RAC65 cells.
AB  - RAC65 is a mutant clone of mouse embryonal carcinoma cells, P19, which does not
      undergo terminal differentiation upon treatment with retinoic acid (RA). RAC65
      cells express a truncated RA receptor alpha (RAR alpha) which, however, does not
      fully explain their defect. Here we show that RAC65 cells exhibit an additional
      defect in RAR alpha mRNA which may reflect a defect in RNA splicing. The parental
      and mutant cells also differ in their capacities to bind [3H]RA into nuclear
      fractions and in expression of cellular RA binding protein (CRABP) mRNA after
      treatment with RA. The combined data suggest that the defect in RAC65 RAR alpha
      results in reduced expression of the CRABP gene after RA treatment and,
      therefore, increased flow of RA into the nucleus.

PMID- 1383036
TI  - Crucial role of pyrophosphate in the aminoacylation of E. coli tRNA(Phe) by yeast
      phenylalanyl-tRNA synthetase.
AB  - Rapid inactivation of the yeast phenylalanyl-tRNA synthetase in the course of
      aminoacylation of the heterologous E. coli tRNA(Phe) is observed. This
      inactivation occurs due to the formation of the tight complex of the enzyme with
      the pyrophosphate formed during the aminoacylation reaction. This complex is
      shown to be the normal intermediate of the reaction. Possible inactivation
      mechanism and correlation between structural differences of yeast and E. coli
      tRNAs(Phe) with the changes in the enzymatic mechanism of aminoacylation are
      discussed.

PMID- 1383037
TI  - Identification and endothelin-induced activation of multiple extracellular signal
      regulated kinases in aortic smooth muscle cells.
AB  - In order to explore intracellular signaling pathways of the mitogenic action of
      endothelin (ET), we examined the effect of ET on activities of extracellular
      signal-regulated kinases (ERKs) in rat aortic smooth muscle cells (SMCs).
      Treatment of rat aortic SMCs with ET-1 increased kinase activities toward myelin
      basic protein (MBP). Both 43- and 41-kDa proteins were activated when kinase
      assays were done in MBP-containing polyacrylamide gels after SDS-PAGE. These
      proteins were identified as ERK1 and ERK2 with immunoprecipitation and
      immunoblotting using antipeptide antibodies, respectively. These results indicate
      that ERKs mediate signal transduction by ET.

PMID- 1383039
TI  - Ion channels from the Bacillus subtilis plasma membrane incorporated into planar
      lipid bilayers.
AB  - Fusion of Bacillus subtilis plasma membrane vesicles with planar lipid bilayers
      induced the appearance of discrete current fluctuations characteristic of ion
      channels. These channels showed a wide range of conductances and kinetic
      behaviors. In 300 mM KCl, their conductances ranged from a few hundreds of pS to
      more than 1 nS, and most of them exhibited several sub-states. The channels
      poorly discriminated between small univalent anions and cations. Some of them
      showed voltage dependence and most of them presented a complex gating kinetics.
      The results are consistent with the hypothesis of the presence in the B. subtilis
      plasma membrane of pores composed of subunits that function cooperatively.

PMID- 1383038
TI  - Regulation of the supramolecular structure and the catalytic activity of
      penicillin acylase from Escherichia coli in the system of reversed micelles of
      Aerosol OT in octane.
AB  - The properties of penicillin acylase from E. coli solubilized by hydrated
      reversed micelles (RM) of Aerosol OT in octane were studied. The dependence of
      catalytic activity on the hydration degree, a parameter which determines the size
      of the micelle inner cavity, has a curve with three optima, each one
      corresponding to the enzyme functioning either in a dimer form (wo = 23) or in a
      form of separate subunits, a heavy one, beta, and a light one, alpha (wo = 20 and
      14, respectively). The reversible dissociation of the enzyme was confirmed by
      ultracentrifugation followed by electrophoresis.

PMID- 1383041
TI  - [Diffuse toxic goiter].

PMID- 1383040
TI  - cDNA encoding the chicken ortholog of the mouse dilute gene product. Sequence
      comparison reveals a myosin I subfamily with conserved C-terminal domains.
AB  - We report the cDNA-deduced primary structure of the chicken counterpart of the
      murine dilute gene product, a member of the myosin I family. Comparison of the
      chicken and mouse sequences reveals a distinct pattern of domains of high and low
      sequence conservation. An internal deletion of 25 amino acids probably reflects
      differential mRNA processing. Compared with other myosin heavy chain molecules,
      sequence similarity is highest with the MYO2 gene product of Saccharomyces
      cerevisiae. The MYO2 protein, implicated in vectorial vesicle transport, is
      homologous to the dilute protein over practically its entire length. In addition,
      the C-terminal domain of the dilute protein is highly similar to a putative
      glutamic acid decarboxylase sequence cloned from mouse brain. Alternatively, this
      closely related clone might represent an isoform of the dilute protein derived
      from a second gene, potentially involved in genetic conditions related to dilute.

PMID- 1383042
TI  - Role of sulfation in post-translational processing of gastric mucins.
AB  - 1. Gastric mucosal segments were incubated in MEM supplemented with various
      sulfate concentrations in the presence of [3H]glucosamine, [3H]proline and
      [35S]Na2SO4, with and without chlorate, an inhibitor of 3'-phosphoadenosine-5'
      phosphosulfate formation. 2. Incorporation of glucosamine and sulfate depended
      upon the sulfate content of the medium and reached a maximum at 300 microM
      sulfate. Introduction of chlorate into the medium, while having no effect on
      protein synthesis as evidenced by proline incorporation, caused, at its optimal
      concentration of 2 mM, a 90% decrease in mucin sulfation and a 40% drop in
      glycosylation. 3. At low sulfate content in the medium and in the presence of
      chlorate, the incorporation of sulfate and glucosamine was mainly into the low
      molecular-weight form of mucin. An increase in sulfate in the medium caused an
      increase in the high molecular-weight form of mucin and in the extent of
      sulfation in its carbohydrate chain. 4. The results suggest that the sulfation
      process is an early event taking place at the stage of mucin subunit assembly and
      that sulfate availability is essential for the formation of the high molecular
      weight mucin polymer.

PMID- 1383043
TI  - beta-Momorcharin, a plant glycoprotein, inhibits synthesis of macromolecules in
      embryos, splenocytes and tumor cells.
AB  - 1. beta-Momorcharin, a glycoprotein isolated from seeds of the bitter gourd,
      inhibited incorporation of [3H]leucine, [3H]uridine and [3H]thymidine into
      trichloroacetic acid-precipitable radioactivity in peri-implantation mouse
      embryos, mouse splenocytes with or without activation by concanavalin A, and
      human squamous carcinoma of the tongue and larynx, but did not affect
      incorporation of the aforementioned radioisotopes into mouse liver cells. 2. The
      results suggest that inhibition of protein, RNA and DNA biosynthesis in embryos,
      splenocytes and tumor cells may represent the mechanism of embryotoxic,
      immunosuppressive and antitumor actions of beta-momorcharin. 3. The results also
      suggest that in mouse liver cells biosynthesis of protein, RNA and DNA was not
      affected by beta-momorcharin.

PMID- 1383044
TI  - Effect of thyroid hormone status on the expression of the mRNAs of components of
      the lipolytic regulatory cascade in brown adipose tissue.
AB  - 1. The levels of mRNAs for RII beta and G beta were about 50% lower in brown
      adipose tissue (BAT) from hyperthyroid than from hypothyroid rats. 2. Treatment
      of hypothyroid rats with T3 resulted in a 50% decrease in mRNAs for RII beta and
      G beta in BAT occurring by 12 hr after treatment. 3. The levels of mRNAs for
      hormone-sensitive lipase, G alpha s and C alpha in BAT were unchanged by thyroid
      hormone status. 4. The results suggest that thyroid hormone may be involved in
      negative regulation of the expression of RII beta and G beta at the
      transcriptional level in BAT.

PMID- 1383045
TI  - Identification of two clock proteins in Acetabularia cliftonii and construction
      of cDNA libraries from Acetabularia cliftonii and Acetabularia mediterranea.
AB  - 1. Two clock proteins were identified in A. cliftonii. The first has a molecular
      weight (mol. wt) of 200 kDa (P200) and its synthesis shows a 24 hr periodicity.
      The second has mol. wt of 130 kDa (P130) and shows a semicircadian rhythm with a
      periodicity of about 12 hr. 2. cDNA libraries from A. cliftonii and A.
      mediterranea were prepared by cloning cDNA in lambda gt10 and lambda gt11,
      respectively. 3. One clone each of the two libraries hybridized with the human
      beta-actin pseudogene. One clone of the A. mediterranea and 4 clones of the A.
      cliftonii libraries hybridized to Chlamydomonas heat-shock gene.

PMID- 1383046
TI  - High-dielectric media for cell electro-manipulation and for electro-kinetic
      methods.

PMID- 1383047
TI  - Definition of an epitope at the nucleotide binding site of the (Ca(2+)-Mg(2+)
      ATPase of sarcoplasmic reticulum by fluorescein labelling.

PMID- 1383048
TI  - Regulated membrane vesicle trafficking: a defect in cystic fibrosis corrected by
      gene transfer.

PMID- 1383049
TI  - A drug-sensitizing RNA interaction of HIV-1 reverse transcriptase.

PMID- 1383050
TI  - Cell-free synthesis of glycolipid candidate precursor(s) for glycosyl
      phosphatidylinositol anchors of Toxoplasma gondii surface proteins.

PMID- 1383051
TI  - The use of an intestinal epithelial cell line as a biological assay system of
      growth factor activity.

PMID- 1383052
TI  - Detection of the Msp I restriction fragment length polymorphism within the COLIA2
      collagen gene.

PMID- 1383053
TI  - Interaction of ruthenium red with the calcium binding sites of sarcoplasmic
      reticulum Ca(2+)-ATPase.

PMID- 1383054
TI  - High resolution two-dimensional electrophoresis of the rat urinary alpha 2u
      globulin fraction indicates further purification by ultrafiltration.

PMID- 1383055
TI  - Developmental effects on the concentration of actin message in mdx and wild-type
      mouse muscle.

PMID- 1383056
TI  - Expression of cytokeratins in epithelial cells isolated from the crypt and villus
      of the small intestine.

PMID- 1383057
TI  - Opposing effects of cyclic AMP and cyclic GMP on ion channels of leech salivary
      gland cells.

PMID- 1383058
TI  - Blood group-related oligosaccharides are ligands in cell-adhesion events.

PMID- 1383059
TI  - Carbohydrate recognition molecules on lymphocytes.

PMID- 1383060
TI  - Antigenic markers of cerebellar modules in the adult mouse.

PMID- 1383061
TI  - Modulation of neuronal Ca(2+)-dependent currents by neurotransmitters, G-proteins
      and toxins.

PMID- 1383062
TI  - Reverse transcriptase of HIV as a target for anti-viral drugs.

PMID- 1383063
TI  - TIBO derivatives: a new class of highly potent and specific inhibitors of HIV-1
      replication.

PMID- 1383064
TI  - Automated simultaneous release of intact and unreduced N and O-linked glycans
      from glycoproteins.

PMID- 1383065
TI  - A new synthetic protease inhibitor, E-3123, prevents lysosomal and mitochondrial
      fragility in rat caerulein-induced pancreatitis.
AB  - The study investigated the protective effect of a new synthetic protease
      inhibitor, E-3123, a 4-guanidinobenzoate methanesulphonate, on the exocrine
      pancreas in caerulein-induced pancreatitis of rats both in vivo and in vitro.
      Hyperamylasaemia, pancreatic oedema and congestion of amylase, as well as
      cathepsin B leakage from lysosomes and malate dehydrogenase leakage from
      mitochondria, were prevented by infusion of 5 mg/kg.h E-3123 particularly when
      infused for 2 h before and during 5 micrograms/kg.h caerulein infusion for 3.5 h.
      The results indicate that E-3123 plays its protective roles against pancreatitis
      in the subcellular compartments such as lysosomes and mitochondria, and that such
      a low molecular weight protease inhibitor as E-3123 may be clinically useful in
      the treatment of acute pancreatitis.

PMID- 1383066
TI  - Steel factor is required for maintenance, but not differentiation, of melanocyte
      precursors in the neural crest.
AB  - Skin melanocytes are derived from neural crest cells that migrate into the dermis
      during embryogenesis. Two mouse mutants, Steel and White dominant-spotting, which
      have defects in melanocyte production, have recently been shown to have deletions
      in the genes that code for a new growth factor, steel factor (SLF), and its
      receptor, respectively. Here, we have investigated the role that SLF plays in
      melanogenesis using cultures of mouse neural crest and found that its primary
      action is the maintenance of melanocyte precursors. It has no effect on the final
      stage of melanocyte differentiation, the production of melanin, which appears to
      require an additional factor whose action is mimicked by the phorbol ester TPA
      (12-O-tetradecanoyl-phorbol-13-acetate).

PMID- 1383067
TI  - G-proteins and hormonal inhibition of insulin secretion from HIT-T15 cells and
      isolated rat islets.
AB  - G-proteins are important mediators of hormonal inhibition of insulin secretion.
      To characterize the pertussis toxin-sensitive substrates present in HIT cell
      membranes, we performed immunoblots with specific antisera and found evidence for
      the presence of Gi alpha 1, Gi alpha 2, Gi alpha 3, and three forms of Go alpha.
      We observed that pertussis toxin-sensitive substrates mediate all of the effects
      of SRIF, and a major portion of the effects of EPI, on insulin secretion from rat
      islets during static incubations. These results agree with our previously
      reported studies examining phasic glucose-induced insulin secretion from HIT
      cells. To ascertain whether inhibition of adenylate cyclase, presumably involving
      coupling of the catalytic subunit to Gi, may be a common mechanism for both
      hormones, we studied the effects of 8-bromo-cyclic AMP and found that this agent
      partially prevented the inhibitory effects of both hormones. We also observed
      that the inhibitory effects of SRIF and EPI on insulin were nonadditive, that
      both hormones were additive to nickel chloride during inhibition of insulin
      release, and that they noncompetitively inhibited glipizide-induced insulin
      secretion through pertussis toxin-sensitive mechanisms. Together, these results
      suggest that both hormones exert their effects on insulin secretion at multiple G
      protein-regulated sites including adenylate cyclase and sites distal to the
      glipizide-binding site on the KATP channel.

PMID- 1383068
TI  - Islet amyloid polypeptide/amylin in pancreatic beta-cell line derived from
      transgenic mouse insulinoma.
AB  - We examined the production and secretion of IAPP in a beta-cell line, MIN6, which
      is derived from an insulinoma obtained by targeted expression of the SV40 T
      antigen gene in a transgenic mouse. RNA blot analysis revealed an abundance of
      IAPP and insulin II mRNA in the cells, findings comparable with those in the
      pancreas of a normal mouse. The presence of IAPP and insulin was confirmed
      immunohistochemically and by RIA. Analysis of the reverse-phase HPLC identified
      IAPP in cells with authentic mouse IAPP. Raising the glucose concentration from
      5.6 to 25 mM failed to induce increments in IAPP and insulin II mRNAs. The cells
      secrete IAPP and insulin for short- and long-term incubations in response to
      concentration of glucose in the medium. These features resemble those of islet
      cells from normal animals. This beta-cell line will aid in analyzing the
      regulation of IAPP gene expression and the mechanisms of IAPP biosynthesis and
      secretion.

PMID- 1383069
TI  - Phosphoribosyl pyrophosphate formation in the rat adrenal gland in relation to
      adrenal growth in experimental diabetes.
AB  - Adrenal growth occurs in experimental diabetes, and evidence exists for increased
      adrenal function. The concentration of PPRibP has been examined in the rat
      adrenal gland at various times after induction of diabetes with STZ, in view of
      the key role it plays in the synthesis of Purs and Pyrs. The PPRibP level was
      exceptionally high in the adrenal gland and increased faster than the rate of
      growth during the initial rapid growth phase--the first 7 days after STZ was
      given; PPRibP synthetase showed a parallel increase. Formation of R5P via the
      oxidative and nonoxidative segments of the PPP also was measured. The oxidative
      enzymes, G-6-PD and 6-PGD, increased in parallel with growth during the early
      phase, but showed a more marked rise during the secondary, slower, growth phase
      seen 6 wk after STZ was given, when this may be associated with the known
      sustained rise in plasma corticosteroids. The nonoxidative enzymes of the PPP, an
      alternate route for the production of R5P, showed smaller changes. The
      specifically high adrenal concentration of PPRibP may be related to the high Km
      for PPRibP (250 microM) of the first enzyme of the de novo pathway of Pur
      synthesis, as such synthesis may be required in the rat to replace the net loss
      of ATP associated with catecholamine secretion. Factors controlling PPRibP
      synthetase and their potential relative importance in the adrenal gland have been
      considered.

PMID- 1383071
TI  - Immunoglobulin M antibody to hepatitis C virus during interferon therapy for
      chronic hepatitis C.
AB  - Testing for immunoglobulin (Ig) M antibody to hepatitis C virus (anti-HCV) as a
      predictive factor of therapeutic response to recombinant interferon alfa (rIFN
      alpha) in chronic hepatitis C was evaluated in 122 patients with IgG anti-HCV.
      IgM anti-HCV was present in the pretreatment sample of 88% of patients who
      responded to treatment, including 20 of 21 (95%) long-term responders and 24 of
      29 (83%) responders who had relapses after cessation of therapy. In contrast, IgM
      anti-HCV was present in only 23 of 39 (59%) nonresponders and 22 of 33 (66%)
      untreated controls (P less than 0.05). The number of cases with detectable IgM
      anti-HCV tended to decrease in responder patients, which was more evident for
      complete responders (42%) than for responders who relapsed (72%). During follow
      up, the antibody became undetectable in the majority of long-term responders (28%
      were still IgM anti-HCV positive) but remained detectable in 69% of responders
      who relapsed (P less than 0.05). No special changes were noted in nonresponder or
      control patients. Thus, testing for IgM anti-HCV may help to identify a subset of
      patients who will benefit from rIFN-alpha therapy in chronic hepatitis C.

PMID- 1383073
TI  - Uptake of 5-hydroxytryptamine in rat isolated atria.
AB  - 1. The mode of 5-hydroxytryptamine (5-HT) uptake by the rat isolated atria was
      studied and compared to noradrenaline (NA) uptake. 2. Rat isolated atria were
      incubated with 14C-5-HT (46 microM) or 3H-NA 0.4 microM). After washing, the
      radioactivity fixed in atria was counted and the total NA, 5-HT and 5
      hydroxyindol-3-acetic acid (5-HIAA) atria contents were measured by HPLC. 3. 14C
      5-HT uptake was reduced in atria from 6-hydroxydopamine (100 mg/kg, i.p., 48 hr
      before experiments) or reserpine (2.5 mg/kg, i.p., 24 and 48 hr before
      experiments) pretreated rats. 4. The incubation of atria with 5-HT (50 microM) at
      the same time as 3H-NA reduced the 3H-NA value fixed. 5. Addition of desipramine
      (1 microM) or hydrocortisone (150 microM) before the incubation of atria with 14C
      5-HT was without any effect on 14C-5-HT uptake. In contrast, fluvoxamine (1
      microM) or indalpine (5 microM) caused a slight inhibition. 6. These data
      indicate that 5-HT is taken into the NA storage vesicles within the atria
      sympathetic nerves. This uptake does not use the NA carrier and involves partly
      the 5-HT carrier. An extraneuronal accumulation was noticed and a part of it is
      intracellular.

PMID- 1383070
TI  - Elevated plasma insulin-like growth factor binding protein-1 levels in type 1
      (insulin-dependent) diabetic patients with peripheral neuropathy.
AB  - Previous studies have suggested that nerve regeneration may be defective in
      patients with diabetic polyneuropathy. Since insulin-like growth factor I (IGF-I)
      has been shown to stimulate nerve regeneration, and IGF binding protein-1 is
      acutely regulated by plasma insulin we have investigated the relationships
      between plasma IGF-I, IGFBP-1, glucose and insulin in Type 1 (insulin-dependent)
      diabetic patients with peripheral polyneuropathy. Plasma samples were taken at
      hourly intervals over an 11-h period (08.00-19.00 hours) in order to characterise
      secretory profiles for 15 Type 1 diabetic patients (eight neuropathic and seven
      non-neuropathic) and eight non-diabetic control subjects. In the non-diabetic
      subjects, mean plasma IGF-I levels were stable throughout the 11-h period with a
      range of 97 micrograms/l-169 micrograms/l. In contrast, mean plasma IGFBP-1
      levels declined steadily from a high level of 1.99 micrograms/l at 08.00 hours to
      approximately one half (0.86 microgram/l) at 15.00 hours. Comparison of areas
      under the curves revealed significant negative correlations between IGFBP-1 and
      glucose (-0.88, p = 0.01), IGFBP-1 and insulin (-0.75, p = 0.016), and IGFBP-1
      and IGF-I (-0.68, p = 0.03). A significant positive correlation was found between
      insulin and IGF-I (+0.89, p = 0.001). The diabetic patients had markedly elevated
      plasma IGFBP-1 levels (area under curve, p = 0.01) and lower plasma IGF-I levels
      (p = 0.033) even though these patients were hyperinsulinaemic throughout the
      study period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383072
TI  - Late stent blockage by blood clot successfully treated by urokinase.

PMID- 1383074
TI  - The effects of P1- and muscarinic-receptor agonists upon cAMP-dependent and
      independent inotropic responses of guinea-pig cardiac preparations.
AB  - 1. The indirect negative inotropic effects of P1- and muscarinic-receptor
      agonists were compared by examining how the responses of isolated guinea-pig left
      atria and papillary muscles to positive inotropes were affected by the presence
      of the P1-receptor agonist, L-PIA or the muscarinic-receptor agonist, carbachol.
      2. The indirect negative inotropic effects of L-PIA and carbachol were similar:
      both attenuated the responses of left atria more effectively than those of
      papillary muscles; and both more effectively attenuated responses to the cAMP
      dependent positive inotropes, isoprenaline and forskolin. 3. However, there were
      differences: L-PIA, but not carbachol, was able at high concentrations to inhibit
      the responses of left atria to the calcium channel opener Bay K 8644; and at
      concentrations that produced similar direct negative inotropic effects, L-PIA
      consistently attenuated the positive inotropes more effectively than carbachol.
      4. These findings are consistent with L-PIA being able to activate an additional
      negative inotropic mechanism that carbachol cannot.

PMID- 1383075
TI  - Silver-induced frog skeletal muscle contraction and its modulation by calcium
      antagonists nifedipine and felodipine and calcium agonist Bay K 8644.
AB  - 1. Ag+ induces one phase of a transient contracture in frog skeletal muscle (0.3
      10 microM) and potentiates twitch tension when the fiber is given continuous
      stimulation. 2. The potentiation of fiber contraction by Ag+ is similar to the
      effect of Ca2+ antagonists nifedipine and felodipine. 3. Bay K 8644 (100 nM)
      potentiates and accelerates Ag(+)-induced tension development and the
      inactivation occurs more rapidly than in the control (Ag+ alone). 4. Two factors
      can be considered to be essential for the induction of Ag+ contracture: (1) a
      certain number of Ag+ ions must bind to free SH groups of the voltage sensor; and
      (2) the binding must occur within a limited time to raise the mechanical
      threshold to induce contracture. 5. All results suggest that Ag+ binding to
      crucial SH groups on the Ca2+ channel may be responsible for the activation of
      muscle contraction, potentiation, and the inhibition of excitation-contraction
      coupling in skeletal muscle.

PMID- 1383076
TI  - Relationship between cyclic AMP-stimulated and native gonadotropin-releasing
      hormone-stimulated gonadotropin release in the goldfish.
AB  - The relationship between drugs elevating intracellular cAMP levels and
      gonadotropin (GTH)-releasing hormone (GnRH) in the stimulation of GTH secretion
      in the goldfish was investigated using dispersed goldfish pituitary cells in
      primary culture. In static incubation experiments, activation of adenylyl cyclase
      by forskolin and the inhibition of cAMP phosphodiesterase by 3 isobutyl-1
      methylxanthine (IBMX) increased cAMP release and stimulated GTH secretion. The
      addition of membrane permeant cAMP analogs, 8-bromoadenosine 3':5'-cyclic
      monophosphate (8Br-cAMP), and dibutyryl cAMP also increased GTH release,
      suggesting that elevation of cAMP levels can induce GTH secretion. In the
      goldfish, dopamine is a physiological inhibitor of GTH release. Application of
      the dopamine agonist apomorphine decreased the GTH responses to forskolin, 8Br
      cAMP, and salmon GTH-releasing hormone (sGnRH). The ability of agents that
      elevate cAMP levels to mimic GnRH action on GTH release suggests that cAMP may
      mediate GnRH-stimulated GTH secretion in the goldfish; however, this possibility
      was not substantiated by results from further experiments. In 2-hr static
      incubation studies, the GTH responses to sGnRH and chicken GnRH-II (cGnRH-II)
      were enhanced by coincubations with forskolin, IBMX, and 8Br-cAMP. The magnitudes
      of these enhancements were at least additive, if not synergistic. The levels of
      cAMP released into the media were unaffected by treatment with sGnRH and cGnRH
      II, either in the absence or in the presence of IBMX. Replacement of normal
      testing media with Ca(2+)-deficient media (without Ca2+ salts and in the presence
      of 0.1 mM EGTA) decreased sGnRH and cGnRH-II stimulation of GTH release but did
      not affect forskolin and 8Br-cAMP actions. These results indicate that sGnRH and
      cGnRH-II stimulation of short term (less than or equal to 2-h) GTH release in the
      goldfish is not mediated by cAMP. The kinetics of the interactions between sGnRH,
      forskolin, and IBMX were also investigated in cell column perifusion studies.
      Applications of 5-min pulses of forskolin and IBMX stimulated rapid increases in
      GTH release; the latencies of these responses were similar to that observed with
      sGnRH. The simultaneous applications of sGnRH with either forskolin or IBMX
      resulted in GTH responses that were of greater magnitude and longer duration than
      those in response to sGnRH alone. These results together indicate that elevation
      of cAMP levels can potentiate the GTH response to the native GnRHs by increasing
      the magnitude of the acute GTH release and by prolonging the duration of GnRH
      action; however, cAMP does not appear to be involved directly in mediating GnRH
      stimulation of GTH release.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1383077
TI  - Somatostatin 14- and somatostatin 25-like peptides in pancreatic endocrine cells
      of Sparus aurata (teleost): a light and electron microscopic immunocytochemical
      study.
AB  - An immunocytochemical investigation demonstrates the presence of somatostatin
      (SST) 14- and salmon somatostatin (sSST) 25-like peptides in two populations of
      somatostatin (D) cells in the islets of gilthead sea bream (Sparus aurata). Both
      cell types were identified by their differing immunoreactivities to the
      somatostatin antisera used. D1 cells in the islet periphery between glucagon
      cells showed sSST 25-like immunoreactivity and contained large moderate to low
      electron-dense granules. D2 cells, present only in the central region of the
      islets between insulin cells, were immunoreactive to the SST 14 antisera and had
      smaller electron-dense granules. In S. aurata, as in other teleosts,
      preprosomatostatin I and II are probably synthesized and processed to SST 14- and
      sSST 25-like peptides, respectively, in different D cell types.

PMID- 1383078
TI  - Endocrine cells and nerves in the pyloric ceca and the intestine of Oncorhynchus
      mykiss (Teleostei): an immunocytochemical study.
AB  - The endocrine cells of rainbow trout pyloric ceca and intestine have been
      investigated immunocytochemically using the avidin-biotin method. Twenty-six
      antisera were tested and 13 endocrine cell types immunoreacted with antisera to
      serotonin, somatostatin-25, bombesin, C-flanking bombesin, substance P, salmon
      PP, NPY, PYY, PP, glucagon, GLP1, Met-enkephalin, and CCK/G. Glucagon and GLP1
      immunoreactivities appear in the same cells. Nerves positive to serotonin,
      substance P, PHI, and VIP were also found. The presence of cells positive to
      somatostatin-25, C-flanking bombesin, and salmon PP are described for the first
      time in fish intestine.

PMID- 1383079
TI  - Frog lymph heart synthesizes and stores immunoreactive atrial natriuretic
      peptide.
AB  - The presence of immunoreactive atrial natriuretic peptide (irANP) and ANP gene
      expression in the frog lymph heart was examined by a radioimmunoassay (RIA)
      combined with HPLC and by Northern blot hybridization of total RNA. Serial
      dilution curve of the lymph heart extract was paralleled with the RIA standard
      curve. The lymph heart contained 153.32 +/- 35.80 pg of irANP/mg of wet tissue.
      The major form of irANP in the frog lymph heart was high molecular weight on
      reverse-phase and gel permeation high performance liquid chromatography as in the
      frog atria and ventricles. The frog lymph heart, as well as frog atria and
      ventricles, was shown to express mRNA coding for ANP. Dense core secretory
      granules similar to those observed in the mammalian atria were also found in the
      frog lymph heart. The presence of irANP and the expression of ANP gene in the
      frog lymph heart suggest that the lymph heart may participate in the regulation
      of homeostasis of lymph circulation and blood volume change through the synthesis
      and release of ANP.

PMID- 1383080
TI  - Extraction and characterization of lipopolysaccharide from Pseudomonas
      pseudomallei.
AB  - The best yield of lipopolysaccharide (LPS) of Pseudomonas pseudomallei GIFU 12046
      was obtained by extraction of defatted cells by phenol/chloroform/petroleum
      ether. The LPS showed a smooth character on SDS-polyacrylamide gel
      electrophoresis and contained D-glucose, L-glycero-D-manno-heptose, and D
      glucosamine as the main sugar components, and 3-hydroxypalmitic acid as an amide
      linked fatty acid. The growth conditions did not affect the electrophoresis
      profile and chemical composition of LPS. 2-Keto-3-deoxyoctonic acid was not
      detectable, and mild acid hydrolysis could not liberate free lipid A, suggesting
      that the linkage between inner core and lipid A was stable against acid
      hydrolysis, and the structure of this region is similar to that of P. cepacia,
      which has close taxonomic relationship with P. pseudomallei.

PMID- 1383081
TI  - The phylogenetic status of Sarcobium lyticum, an obligate intracellular bacterial
      parasite of small amoebae.
AB  - A 16S rRNA gene of the obligate intracellular bacterial parasite Sarcobium
      lyticum was amplified using the polymerase chain reaction in combination with
      site-specific primers. The amplified DNA was cloned, sequenced and compared with
      other bacterial 16S rRNA sequences. The analysis revealed that S. lyticum belongs
      to the gamma subclass of the Proteobacteria and shows the closest relationship to
      an intracellular Legionella species recovered by amoebal enrichment from the
      sputum of a patient with pneumonia. S. lyticum could be detected in situ with a
      fluorescent oligonucleotide probe by whole cell hybridization.

PMID- 1383082
TI  - Studies on the ribosomal RNA operons of Listeria monocytogenes.
AB  - A 23S rRNA gene of Listeria monocytogenes was cloned into pUC19 on a 6.2-kb Pst I
      fragment. Hybridisation studies demonstrated the presence of the 5S and partial
      16S rRNA genes within the clone. The nucleotide sequence of the region encoding
      the 23S rRNA was found to be highly homologous with those of other low G + C Gram
      positive bacteria. The 16S-23S intergenic spacer region was amplified using PCR
      technology and revealed two product sizes, the larger of which contained
      tRNA(Ala) and tRNA(Ileu) genes. Further tRNA genes were found downstream of the
      5S rRNA gene.

PMID- 1383083
TI  - Taxonomic studies on a psychrophilic Clostridium from vacuum-packed beef:
      description of Clostridium estertheticum sp. nov.
AB  - Taxonomic studies were performed on an anaerobic Gram-positive, spore-forming,
      psychrophilic bacterium originally isolated from spoiled vacuum-packed
      refrigerated beef. Based on the present finding it is proposed that this unknown
      psychrophilic bacterium be classified as a new species of the genus Clostridium,
      as Clostridium estertheticum sp. nov. The type strain is NCIMB 12511.

PMID- 1383084
TI  - Evidence for a close genealogical relationship between Afipia (the causal
      organism of cat scratch disease), Bradyrhizobium japonicum and Blastobacter
      denitrificans.
AB  - The primary structures of the small subunit rRNA of Bradyrhizobium japonicum and
      Blastobacter denitrificans were determined by direct sequencing of enzymatically
      amplified DNA. Comparative sequence analysis revealed that Bradyrhizobium
      japonicum and Blastobacter denitrificans are members of the alpha-2 subgroup of
      the Proteobacteria and show a very close phylogenetic relationship with the genus
      Afipia.

PMID- 1383085
TI  - Molecular cloning and sequence analysis of the gene coding for the 57-kDa major
      soluble antigen of the salmonid fish pathogen Renibacterium salmoninarum.
AB  - The complete sequence coding for the 57-kDa major soluble antigen of the salmonid
      fish pathogen, Renibacterium salmoninarum, was determined. The gene contained an
      opening reading frame of 1671 nucleotides coding for a protein of 557 amino acids
      with a calculated M(r) value of 57,190. The first 26 amino acids constituted a
      signal peptide. The deduced sequence for amino acid residues 27-61 was in
      agreement with the 35 N-terminal amino acid residues determined by
      microsequencing, suggesting the protein is synthesized as a 557-amino acid
      precursor and processed to produce a mature protein of M(r) 54,505. Two regions
      of the protein contained imperfect direct repeats. The first region contained two
      copies of an 81-residue repeat, the second contained five copies of an unrelated
      25-residue repeat. Also, a perfect inverted repeat (including three in-frame UAA
      stop codons) was observed at the carboxyl-terminus of the gene.

PMID- 1383086
TI  - Mice develop normally without tenascin.
AB  - Tenascin, an extracellular matrix protein, is expressed in an unusually
      restricted pattern during embryogenesis and has been implicated in a variety of
      morphogenetic phenomena. To directly assess the function of tenascin in vivo, we
      generated mutant mice in which the tenascin gene was nully disrupted by replacing
      it with the lacZ gene. In mutant mice, lacZ was expressed in place of tenascin,
      and no tenascin product was detected. Homozygous mutant mice were, however,
      obtained in accordance with Mendelian laws, and both females and males produced
      offspring normally. No anatomical or histological abnormalities were detected in
      any tissues, and no major changes were observed in distribution of fibronectin,
      laminin, collagen, and proteoglycan. The existence of these mutant mice, lacking
      tenascin yet phenotypically normal, casts doubt on the theory that tenascin plays
      and essential role in normal development.

PMID- 1383087
TI  - Developmental abnormalities in Steel17H mice result from a splicing defect in the
      steel factor cytoplasmic tail.
AB  - The murine dominant White spotting (W) and Steel (Sl) loci encode the c-kit
      tyrosine kinase receptor and its cognate ligand steel factor (SLF), respectively.
      Mutations at either locus produce deficiencies in the same three migratory cell
      populations--those giving rise to pigment cells, germ cells, and blood cells. The
      identification of the gene products of these two loci combined with the plethora
      of W and Sl mutations available for molecular analysis offers a unique
      opportunity to dissect the role of a tyrosine kinase receptor and its cognate
      ligand during development in a fashion not possible for most other mammalian
      genes. Among the most interesting Sl mutations available for study are those that
      induce sterility in only one sex. In studies described here, we show that one of
      these alleles, Sl17H, which in the homozygous condition induces sterility in
      males but not females, is the result of a splicing defect in the SLF cytoplasmic
      tail. We also characterize the nature of the germ cell defects in male and female
      Sl17H mice and show that both sexes are affected equally during embryonic but not
      postnatal development. These studies provide new insights into the role of SLF in
      germ cell development and indicate that the cytoplasmic domain of SLF is
      important for its normal biological function.

PMID- 1383088
TI  - Parental imprinting: potentially active chromatin of the repressed maternal
      allele of the mouse insulin-like growth factor II (Igf2) gene.
AB  - The mouse insulin-like growth factor II (Igf2) gene, which is located on distal
      chromosome 7 (Chr7), has been shown previously to undergo tissue-specific
      parental imprinting. This imprinting results in expression of Igf2 from the
      paternally inherited chromosome and repression of the maternally inherited allele
      in most tissues of the developing embryo. We are using embryos with the maternal
      duplication and paternal deficiency of distal Chr7 to characterize the mechanism
      that underlies repression of the maternal allele. We show that the chromatin of
      the 5' region of the repressed Igf2 allele is potentially active for
      transcription rather than heterochromatic. In particular, a CpG island that
      comprises one of the two strong promoters is unmethylated at both parental
      alleles, and DNase I hypersensitive sites in and around the strong promoters are
      consistently present on both parental chromosomes. In agreement with the
      chromatin state, primary transcripts from the maternal Igf2 allele have been
      detected at low but significant levels. These findings differ from observations
      in other instances of imprinting, namely, X-chromosome inactivation and transgene
      imprinting in mice. Although no parent-specific differences were detected in
      either DNA methylation or sensitivity to nucleases at these promoters, we have
      observed parental methylation differences in a region several kilobases upstream
      of the first exon. The differential activity of the parental Igf2 alleles could
      be achieved through epigenetic modifications situated outside the promoters or by
      subtle and yet unidentified modifications at the promoters.

PMID- 1383089
TI  - Developmental regulation of a complete 70-kb human beta-globin locus in
      transgenic mice.
AB  - We have used a linker-based ligation strategy to combine two 35-kb cosmid inserts
      from the human beta-globin locus into one linear fragment containing the entire
      locus. This 70-kb fragment was introduced into transgenic mice by microinjection
      of fertilized eggs. Southern blot analysis showed that a single complete
      transgene locus can be introduced into the germ line with high efficiency.
      Analysis of the expression patterns of the locus during development shows that
      the epsilon-globin gene behaves as a purely embryonic gene, the gamma-globin gene
      as an embryonic and early fetal gene, and the beta-globin gene as a fetal adult
      gene. Quantitation of expression showed that the levels of transcription of the
      epsilon- and gamma-globin genes are reversed relative to their mouse homologs but
      that the total output of the human and mouse loci is constant during development.
      These results suggest that multiple changes in DNA sequences and transcription
      factor balance must have occurred for the human gamma-globin gene to have evolved
      into a fetal gene.

PMID- 1383090
TI  - Escherichia coli single-stranded DNA-binding protein is a supercoiled template
      dependent transcriptional activator of N4 virion RNA polymerase.
AB  - Coliphage N4 is a double-stranded DNA virus that requires the sequential activity
      of three different RNA polymerases during infection. The N4 virion RNA
      polymerase, which is carried in the virion and is injected with the DNA at the
      start of infection, is responsible for the synthesis of N4 early RNAs. In vitro,
      the virion RNA polymerase can transcribe double-stranded N4 DNA accurately and
      efficiently but only when the DNA is denatured. We have shown previously that the
      activity of DNA gyrase is required for in vivo early N4 transcription. We report
      here that Escherichia coli single-stranded DNA-binding protein (SSB) is also
      required for N4 early transcription. In vitro, linear or relaxed templates cannot
      be activated by SSB; however, supercoiled template and SSB allow the virion
      polymerase to recognize its promoters on duplex DNA and activate transcription.
      The effects of supercoiling are limited to transcript initiation and are not
      required for transcript elongation. The activation is specific for SSB; no other
      single-stranded DNA-binding proteins can substitute. Therefore, SSB is one of a
      small number of proteins that function to stimulate both replication and
      transcription. The basis for the specificity of SSB, the mechanism of
      transcriptional activation by SSB and template supercoiling, and their role in
      the N4 transcriptional program during development are discussed.

PMID- 1383091
TI  - Translational initiation factors IF-1 and eIF-2 alpha share an RNA-binding motif
      with prokaryotic ribosomal protein S1 and polynucleotide phosphorylase.
AB  - Initiation of translation is a complicated process involving numerous accessory
      factors whose functions remain incompletely understood. Bacterial ribosomal
      protein S1 is known to contain a repeated sequence motif (S1-RM), also found in
      polynucleotide phosphorylase, that is thought to be involved in binding to RNA.
      Using the technique of profile analysis, the S1-RM can also be found in bacterial
      and chloroplast translation initiation factor IF-1 sequences, and in the
      sequences of eukaryotic translation initiation factor eIF-2 alpha chains. The
      significance of the similarity of the sequences is very high suggesting that the
      occurrence of the S1-RM in these diverse proteins represents homology. The
      similarity of S1 to IF-1 further suggests that S1 has evolved from an IF-1 like
      ancestor, and therefore that the two proteins have a similar or competitive
      function. The most obvious common function of the proteins containing the S1-RM
      seems to be RNA binding, suggesting that IF-1 and eIF-2 alpha may bind to RNA.

PMID- 1383092
TI  - Efficient amplification of Drosophila simulans copia directed by high-level
      reverse transcriptase activity associated with copia virus-like particles.
AB  - The number of retrotransposon copia per genome in Drosophila melanogaster
      cultured cells is two to three times higher than that in D. melanogaster embryo
      cells. Here, we have found that the genome of the related species, Drosophila
      simulans, contains in cultured cells more efficiently amplified copia DNA
      (approximately ten fold). Furthermore, we analyzed copia virus-like particles
      (VLPs) prepared from D. melanogaster and D. simulans cultured cells, which
      contain copia RNA and reverse transcriptase (RT) activity, and thus, play a major
      role in copia replication. The RT activity associated with the D. simulans VLPs
      was 25 times higher than that associated with the D. melanogaster VLPs. Taken
      together with the fact that copia is believed to transpose through an RNA
      intermediate, these results suggest that the amplification of copia DNA should
      relate to copia RNA-mediated transposition, and the higher RT activity associated
      with the D. simulans VLPs would lead to the efficient amplification of copia DNA.
      In a comparison between D. melanogaster and D. simulans copia nucleotide (nt)
      sequences, five nt substitutions, which cause the respective amino acid changes,
      were found in the copia RT-coding region. Polymerase chain reaction direct
      sequencing showed that these five substitutions are the vast majority in each
      Drosophila species. The substitutions, therefore, may be responsible for the high
      level of the RT activity associated with the D. simulans VLPs.

PMID- 1383093
TI  - Structure and expression of the gene encoding mouse t-complex polypeptide (Tcp
      1).
AB  - The nucleotide (nt) sequence of the structural gene (Tcp-1) encoding mouse t
      complex polypeptide 1 (TCP-1) has been determined. The nt sequence extending to
      10,043 bp shows that the Tcp-1 gene is divided into 12 exons, 11 introns and 5'-
      and 3'-flanking regions. The Tcp-1 gene has a tight cluster of major
      transcription start points (tsp). Two GC boxes, one CCAAT box and some other
      possible regulatory elements are located in the region upstream from the tsp, but
      no TATA box was found. Extending from the 5'-flanking region to the first intron,
      a CpG dinucleotide-rich cluster is located. In addition, Tcp-1 gene transcripts
      in mouse organs, embryos and cultured cells were analyzed by Northern blotting.
      The Tcp-1 mRNA is enriched not only in testes, but also in early post
      implantation embryos and some cultured cell lines, as compared with mouse organs
      other than the testis. The amount of Tcp-1 mRNA in embryos decreases during
      development. These results suggest that the expression of the Tcp-1 gene may be
      regulated spatially and temporally in embryonic and adult mice by transcriptional
      control or by mRNA stability.

PMID- 1383094
TI  - Use of an epitope-tagged cDNA library to isolate cDNAs encoding proteins with
      nuclear localization potential.
AB  - We have combined epitope tagging with an expression cDNA library in order to
      isolate cDNAs encoding nuclear proteins. This system allows us to detect proteins
      expressed from the cDNA library by using antibodies against the epitope tag. As a
      tag, we used the 85-aa N-terminal peptide of the SV40 T antigen which lacks the
      nuclear localization signal (NLS). A strong expression vector, pEF204 [Kim et
      al., Gene 91 (1990) 217-223], was modified into an epitope-tagging vector, pTkim,
      by putting the tag-coding region and a cDNA cloning site immediately after its
      promoter. From cDNA libraries constructed using pTkim, we isolated eight cDNA
      clones whose tagged proteins were localized within the nuclei. From partial
      sequence analysis, two cDNAs were shown to code for the ribosomal (r-) proteins,
      simian L44 and human L21, and the others were shown to be new. Furthermore, six
      cDNAs including those encoding the r-proteins could direct a non-karyophilic T
      antigen [Fischer-Fantuzzi et al., Virology 153 (1986) 87-95] into nuclei, showing
      that they have NLSs. These results indicate that this system is useful for
      isolating new cDNAs which code for nuclear proteins.

PMID- 1383095
TI  - A nuclear gene encoding beta-amylase of sweet potato.
AB  - A nuclear AmyB gene from sweet potato encoding beta-amylase (beta Amy) that is
      abundant in tuberous roots and inducible in other organs by an exogenous supply
      of sucrose or polygalacturonic acid, was isolated and characterized. Genomic
      Southern blot hybridization, restriction maps of independently isolated phage
      lambda genomic clones, and the nucleotide sequence of AmyB compared with that of
      the cDNA, all suggested that beta Amy of sweet potato is encoded by a gene that
      is present in a single copy per haploid genome. In the sequence of AmyB, the
      sequence that is identical to that of the cDNA was split into seven exons by six
      introns, and the transcription of this gene starts from multiple sites 26 to 30
      bp downstream from a potential TATA-box sequence, 5'-TATATAA. In the 5'-upstream
      region of AmyB, there are sequences homologous to those conserved in the 5'
      upstream regions of genes encoding sporamin, which are regulated similarly to
      AmyB. The 5'-upstream region of AmyB also contains sequences to which several
      previously known plant nuclear factors bind.

PMID- 1383096
TI  - Production and secretion in CHO cells of the extracellular domain of AMOG/beta 2,
      a type-II membrane protein.
AB  - A hybrid gene consisting of the sequences coding for the signal peptide and N
      terminus of a type-I membrane protein, the neural cell adhesion molecule (N-CAM),
      and the extracellular domain of the adhesion molecule on glia (AMOG/beta 2), a
      type-II membrane protein, was constructed. The sequence was inserted into a
      eukaryotic expression vector containing the human cytomegalovirus promoter and
      the glutamine synthetase selection marker, and used to transfect Chinese hamster
      ovary cells. The resulting stably transformed cell lines produced large amounts
      of soluble recombinant AMOG/beta 2 (reAMOG/beta 2), which was secreted into the
      culture medium as a heavily glycosylated 40-55-kDa protein. N-terminal sequence
      analysis revealed that the protein is not cleaved at the natural signal peptide
      cleavage site of N-CAM, but two amino acids (aa) further downstream. Treatment of
      reAMOG/beta 2 with N-glycosidase F (GlycoF) reduced the molecular mass to 27 kDa,
      corresponding to the calculated mass of the unglycosylated form. In contrast to
      AMOG/beta 2 isolated from mouse brain, which is sensitive to endoglycosidase H,
      the immunoaffinity-purified re-protein is more resistant to this treatment,
      indicating that the sugars attached to reAMOG/beta 2 are mainly of the complex
      type. Our results demonstrate the feasibility of secreting the extracellular
      domain of a type-II membrane protein, which is usually inserted into the membrane
      with the C terminus facing the extracellular side.

PMID- 1383097
TI  - Production of reactive oxygen by mitochondria from normoxic and hypoxic rat heart
      tissue.
AB  - Reactive oxygen species (ROS), which may be involved in ischemic or reperfusion
      heart injury, can be produced by mitochondria. Previous work indicated that
      coupled mitochondria from ischemic heart tissue incubated in calcium-free medium
      produced less ROS than normal. The effects of calcium, which may be elevated in
      hypoxic or ischemic tissue, were not examined. The relative production of ROS by
      mitochondria from normoxic or hypoxic rat heart tissue was estimated by measuring
      the oxidation of dichlorofluorescin to the fluorescent compound,
      dichlorofluorescein. ROS were detectable during succinate-stimulated State 4
      respiration. In the absence of calcium, mitochondria from hypoxic (60 min) heart
      tissue produced less ROS than mitochondria from normoxic heart tissue. In the
      presence of 0.1, 1 or 10 microM calcium, ROS produced by hypoxic mitochondria
      were increased to normoxic levels. While function was depressed in mitochondria
      from hypoxic tissue, the presence of 0.1 and 1 microM calcium had no further
      effect. Respiration was uncoupled in the presence of 10 microM calcium in
      mitochondria from both normoxic and hypoxic heart tissue. ROS production was
      increased in mitochondria from hypoxic tissue with both increasing concentrations
      of calcium and increasing duration of exposure. ROS production in mitochondria
      from normoxic heart tissue was only stimulated after 200 or more seconds of
      exposure to 1 or 10 microM calcium. Production of ROS in mitochondria from
      hypoxic tissue in the presence of 1 microM calcium was inhibited by rotenone
      (80%), ruthenium red (69%), and a combination of these agents (96%). In contrast,
      ruthenium red had no effect on ROS production by mitochondria from normoxic heart
      tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383098
TI  - Duodenal ulcer: a model of impaired mucosal defence.
AB  - There is a new model of chronic duodenal ulcer in which the ulcer is generated by
      irradiating the lower mediastinum of mice with a single dose of 18 Gy 250 kV x
      rays. Single ulcers develop in the proximal duodenum of about half the animals.
      Previous studies have shown a remarkable morphological and behavioural similarity
      to duodenal ulcer in man. Ulceration occurs because of an imbalance between
      aggressive and defensive forces within the duodenum and an attempt has been made
      to elucidate the pathomechanism of this ulcer by determining acid and pepsin
      secretion. The basal and pentagastrin stimulated secretion of acid, pepsin, and
      histamine were measured and no changes in acid or pepsin secretion were shown to
      occur (risk of type II error < 1%). It is therefore concluded that this chronic
      ulcer is a model of impaired duodenal defence.

PMID- 1383099
TI  - Does the somatostatin analogue octreotide protect against ERCP induced
      pancreatitis?
AB  - This study evaluates the effect of the long acting somatostatin analogue
      octreotide on biochemical and clinical parameters of endoscopic retrograde
      cholangiopancreatography (ERCP) induced pancreatitis. Altogether 245 patients
      were randomised to receive either octreotide or isotonic saline. Octreotide (100
      micrograms) was administered intravenously five minutes before ERCP and
      subcutaneously 45 minutes after ERCP. There were no significant differences in
      the median serum amylase and lipase activities at baseline, eight, and 24 hours
      after ERCP. Five patients (2%) developed clinical pancreatitis--three in the
      octreotide and two in the placebo groups. Excluding patients who developed
      pancreatitis, 43 (18%) developed abdominal pain after ERCP--21 in the octreotide
      and 23 in the placebo groups. There were no significant differences in the median
      serum amylase and lipase values between the treatment groups. None of the 52
      patients who had therapeutic interventions developed pancreatitis. This study
      suggests that octreotide may not protect against ERCP induced pancreatitis.

PMID- 1383100
TI  - Palliative removal of a giant polypoid 'carcinosarcoma' of the oesophagus by YAG
      laser photocoagulation of the tumour stalk.
AB  - Dysphagia in a 79 year old lady was caused by a giant polypoid tumour in mid
      oesophagus. Surgery was not appropriate. Shrinkage of the tumour and its eventual
      detachment were achieved by stopping its blood supply by YAG laser
      photocoagulation of the tumour stalk. Good, temporary palliation of the dysphagia
      was achieved.

PMID- 1383101
TI  - Granular acute lymphoblastic leukemia in children. "Aieop Cooperative Group for
      Cytology of Acute Leukemias".
AB  - BACKGROUND: Granular acute lymphoblastic leukemia (ALL) is a rare morphological
      variant of ALL, characterized by cytoplasmic azurophil granules or inclusions,
      positive for aspecific esterase and acid phosphatase, with heterogeneous features
      at the ultrastructural level. METHODS: In an attempt to determine whether the
      presence of granules or inclusions marks a biologically distinct variety of ALL
      with peculiar clinical features, a prospective morphological review was
      undertaken of children entering AIEOP protocols for ALL in the period from 1985
      to 1989. RESULTS: Of 531 cases examined, 16 (3%) were found to have greater than
      1% granular bone marrow blasts, with 7 cases (1.3%) having greater than 10%. The
      presence of granules or inclusions was associated with the immunophenotype of
      "common" ALL. There was no clear association with FAB type L1 or L2 nor with
      particular clinical or hematological findings at presentation. Complete remission
      was achieved in all cases; one patient died of infection in remission at 3 months
      and 2 patients relapsed after 12 and 32 months, respectively, while the others
      are still in remission after a minimum follow-up of 24 months. CONCLUSIONS: In
      conclusion, granular morphology seems to have no prognostic importance in
      children ALL.

PMID- 1383102
TI  - Severe respiratory depression after autologous bone marrow infusion.

PMID- 1383103
TI  - Beta-globin haplotype and XmnI polymorphism at position G (gamma)-158 and HbF
      production in Fanconi's anemia.
AB  - BACKGROUND: Patients with aplastic anemia show to a variable degree an increase
      of the red blood cell volume and percentage of HbF. The extent of HbF
      reactivation in sickle cell anemia and thalassemia major is related to the
      presence of XmnI polymorphism at -158 G (gamma). In this study, we have
      investigated whether in Fanconi's anemia the increase of the HbF is also related
      to the XmnI polymorphism. METHODS: Restriction site polymorphisms in the beta
      globin gene cluster were analyzed to define the beta-globin haplotype. The
      presence of a C --> T substitution at position -158 G (gamma) was investigated by
      XmnI digestion. RESULTS: We found that patients with the XmnI site at -158 G
      (gamma), which was contained either in the 5' -+-++ or in the rare -+--- sub
      haplotype, tend to have higher HbF and MCV values. The differences between XmnI
      positive and XmnI negative patients were highly significative (p less than
      0.0025) for the MCV values, but barely significant for HbF levels (p less than
      0.05). CONCLUSIONS: Our results suggest that in Fanconi's anemia both the extent
      of HbF reactivation and the fetal-like erythropoiesis, which is responsible for
      high MCV, are at least partially related to the beta-globin haplotype.

PMID- 1383104
TI  - Identification of anti-platelet autoantibodies by western blot in 45 patients
      with idiopathic thrombocytopenic purpura (ITP).
AB  - BACKGROUND: In sera and platelet eluates of ITP patients, antigen specificity was
      widely studied by means of sensitive methods including immunoprecipitation,
      monoclonal antibody immobilization, and immunoblot. These studies indicated that
      GPIIb-IIIa were the main epitopes of ITP autoantibodies. METHODS: We studied the
      specificity of antiplatelet autoantibodies in 45 patients with acute and chronic
      ITP. Patient sera were tested by Western blot on separated platelet proteins in
      non-reducing conditions; antibody binding was identified using biotinconjugated
      anti-human IgG and avidin-peroxidase. RESULTS: Two main nonspecific bands of 200
      and 125 kD were visible using normal serum; the first referred to platelet IgG,
      and the second was due to a naturally occurring antibody towards an internal
      protein. Twenty-five sera (55%) stained one (n = 11), two (n = 7), three (n = 3)
      or four (n = 4) specific bands. In patients with chronic ITP there was a
      prevalence of multiple bands. The relative molecular weights of the recognized
      antigens were in the range of 140-160, 80-100, 50-70 and 40 kd. The 80-100
      epitope was recognized as a membrane protein in only 40% of sera, and it was
      partially characterized as GPIIIa in 4 patients. The other stained epitopes were
      absorbed by platelet lysate and then identified as internal proteins.
      CONCLUSIONS: This finding might be related to sensitization to antigens exposed
      by platelets during immune damage, and may pose an important problem in the
      identification with the immunoblot technique of target antigens responsible for
      immune sequestration.

PMID- 1383105
TI  - Effect of in vivo treatment with rh GM-CSF on in vitro growth of haematopoietic
      progenitors in patients with myelodysplastic syndromes.
AB  - BACKGROUND: Recombinant (r) human (h) granulocyte/macrophage colony stimulating
      factor (rh GM-CSF) has been shown to increase the number of peripheral blood (PB)
      neutrophils, eosinophils and monocytes in myelodysplastic syndromes (MDS). The
      aims of this study were: 1) to evaluate the effect of rh GM-CSF therapy on the in
      vitro growth of granulocyte-erythroid-macrophage-megakaryocyte colonies (CFU
      GEMM), erythroid colonies (BFU-E), and granulocyte-macrophage colonies (CFU-GM)
      in patients with MDS; 2) to assess in these patients, while they are being
      treated in vivo with rh GM-CSF, the possible additive effect of rh IL-3 and rh G
      CSF on the in vitro growth of haematopoietic progenitors. METHODS: The in vitro
      growth of CFU-GEMM, BFU-E and CFU-GM was studies in 10 myelodysplastic (MDS)
      patients, before and after in vivo administration of rh GM-CSF. RESULTS: After rh
      GM-CSF administration, the number of CFU-GM increased in all standard risk MDS
      patients. In 2 out of 5 cases, this effect was more pronounced and persisted up
      to 30 days after the end of rh GM-CSF treatment. On the other hand, the number of
      CFU-GEMM and BFU-E was substantially unchanged. When rh GM-CSF, rh G-CSF and rh
      IL-3 were added in vitro alone or in combination as the source of colony
      stimulating activity, no significant increase of the CFU-GM colony number was
      noticed. CONCLUSIONS: Rh GM-CSF therapy appears useful for increasing the number
      of peripheral blood granulocytes and of marrow CFU-GM in standard-risk MDS
      patients. High-risk MDS patients are far less responsive to rh GM-CSF treatment,
      probably reflecting a more aggressive and/or advanced disease.

PMID- 1383106
TI  - The human platelet membrane glycoprotein IIb/IIIa complex: a multi functional
      adhesion receptor.
AB  - The glycoprotein GPIIb/IIIa complex is a major constituent of the platelet
      membrane; it plays an important role in platelet adhesion and aggregation. The
      complex is a member of the integrin superfamily. Integrins are related membrane
      receptors which mediate the adhesive interactions of a variety of cells; they
      specifically recognize the arginine-glycine-aspartic acid (RGD) sequence present
      in several adhesive proteins. The GPIIb/IIIa complex of activated platelets can
      bind fibrinogen, von Willebrand factor, fibronectin, vitronectin and
      thrombospondin. Platelets are activated by a variety of signals including
      extracellular matrix molecules and soluble factors; upon platelet activation the
      complex undergoes a conformational change, thus permitting the macromolecular
      ligands access to their binding sites. In turn, fibrinogen binding results in a
      receptor modification and neoantigens exposure; such events may participate in
      signal transduction. The adhesive proteins compete reciprocally for binding to
      GPIIb/IIIa, and the complex binds to different domains of them, thus creating
      multiple interactions with the ligands.

PMID- 1383107
TI  - Combined modality (ABVD plus radiotherapy) versus radiotherapy in the management
      of early stage (IIA) Hodgkin's disease with mediastinal involvement.
AB  - The aim of this study was to establish whether combined modality treatment (ABVD
      plus radiotherapy) can reduce the risk of relapse in Hodgkin's disease patients
      with mediastinal involvement, as compared to radiotherapy alone. The results
      obtained suggest that one course of ABVD before irradiation can reduce the
      incidence of relapse. These findings, however, should be considered preliminary
      and need to be confirmed in larger studies.

PMID- 1383108
TI  - Effect of Caralluma tuberculata on the cytological and biochemical changes
      induced by cyclophosphamide in mice.
AB  - Treatment with Caralluma tuberculata extract induced complex biochemical and
      cytological changes in mice. Its cytotoxicity in the bone marrow cells of mice
      was comparable with that of the standard drug cyclophosphamide (CP); however,
      unlike CP, C. tuberculata was not clastogenic (as shown by the micronucleus
      assay). A dose-dependent decrease in the RNA content of liver and testes was
      produced by C. tuberculata treatment whereas there was no effect on the content
      of nucleic acid and protein in the brain. In the extract-treated animals there
      was a significant and dose-dependent increase in the DNA content of the liver,
      with a negligible effect on the protein content. Combined treatment with C.
      tuberculata and CP showed that C. tuberculata diminished the effect of CP on DNA
      levels; however, RNA levels were further suppressed, resulting in increased
      cytotoxicity. Pretreatment with C. tuberculata extract significantly reduced the
      clastogenicity of CP. These results indicated the involvement of different
      phytoconstituents acting by different routes.

PMID- 1383109
TI  - A sensitive sandwich enzyme immunoassay for gamma-seminoprotein and its
      application to sex discrimination of blood and bloodstains.
AB  - A sensitive sandwich enzyme immunoassay for gamma-seminoprotein (p30, prostate
      specific antigen) is described for sex discrimination of blood and bloodstains. A
      polystyrene ball coated with rabbit anti-gamma-seminoprotein IgG was incubated
      with gamma-seminoprotein and, after washing, with affinity-purified rabbit anti
      gamma-seminoprotein Fab'-horseradish peroxidase conjugate. Peroxidase activity
      bound to the polystyrene ball was assayed by fluorometry using 3-(4
      hydroxyphenyl)propionic acid as hydrogen donor. The detection limit of gamma
      seminoprotein was 0.15 pg per assay. Blood levels of gamma-seminoprotein,
      measured using 1-10 microliters of blood, were at least 3.3-fold higher in male
      adults than in female adults. The ratio of gamma-seminoprotein in terms of pg to
      hemoglobin in terms of mg was significantly higher in male adults than in female
      adults. Thus, the measurement of gamma-seminoprotein or both gamma-seminoprotein
      and hemoglobin was useful for the discrimination of blood and bloodstains of male
      and female adults, although with some limitations.

PMID- 1383110
TI  - [The pathogenesis of psoriasis--new results].
AB  - A great deal of new immunological, biochemical, and cell biological information
      has been published on the pathogenesis of psoriasis. Many of these findings must
      be considered to be epi-phenomena of the inflammatory reaction (clinical
      correlate--erythema) and hyperproliferation of keratinocytes (scaling). The
      mechanisms of the psoriatic inflammatory reaction and of the specific neutrophil
      infiltration can now be more readily understood following the discovery of
      adhesion molecules, and the identification of new mediators--in particular NAP
      1/IL-8. Proliferation-promoting factors for keratinocytes in vitro, that is,
      possible mediators of psoriatic scaling, are listed, and currently known changes
      in expression and concentration in psoriatic lesions are discussed.

PMID- 1383111
TI  - Influence of age at time of surgery on pre-operative left ventricular mass and
      postoperative outcome of Fontan operation in children with tricuspid atresia and
      native pulmonary stenosis.
AB  - Purpose of this study was to examine the influence of early (less than two and
      half years) versus later (greater than four years) age at time of Fontan type
      palliation in tricuspid atresia with native pulmonary stenosis on outcome with
      special reference to left ventricular mass and function. Among the 21 patients
      with tricuspid atresia, twelve (group A) underwent a Fontan type palliation at a
      median age of one (.6 to 2.5) years and nine (group B) at a median age of 7.5
      (4.8 to 28) years. Left ventricular mass was assessed by cross-sectional
      echocardiography in the apical two and four chamber view. Mass was calculated as
      difference between epicardial and endocardial volume x 1.05 (specific gravity of
      heart muscle). Mass divided by volume at end-diastole yielded the mass/volume
      index. There was a weak correlation between age and left ventricular mass with an
      r-value of 0.74. Ejection fraction was calculated from the endocardial volume
      measurements at end-diastole and end-systole. Patient data were compared to
      normal values previously established in 95 controls, who were age-matched for the
      patients. Immediately before surgery left ventricular mass was significantly
      higher in the nine patients, who underwent surgery at a later age. While
      postoperative stay in hospital and duration of treatment in the intensive care
      unit did not differ significantly between both groups, the incidence of pleural
      and pericardial effusions and the duration of insertion of drainage tubes for
      these effusions differed significantly with the group A patients (under two and
      half years of age) doing better.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383112
TI  - Bidirectional cavopulmonary anastomosis in congenital heart disease. Functional
      and clinical outcome.
AB  - The bidirectional cavopulmonary anastomosis is a surgical procedure suitable for
      patients with cyanotic congenital heart disease and univentricular physiology.
      This operation is able to increase the effective pulmonary blood flow without any
      additional load on the cardiac work and without any further distortion on the
      pulmonary artery branches. The cavopulmonary anastomosis can represent the first
      stage for patients destined for Fontan repair or a definitive palliative
      operation in high risk Fontan candidates. In order to test the hypothesis of a
      definitive palliation by cavopulmonary anastomosis in this kind of patients, we
      evaluated the hemodynamic data before and after this surgical approach and
      compared these data with their clinical and functional outcome. We evaluated 74
      patients submitted to bidirectional cavopulmonary anastomosis by either
      hemodynamic or functional evaluation. End-diastolic and end-systolic ventricular
      volumes were significantly reduced by bidirectional cavopulmonary anastomosis (p
      less than 0.0005). Despite these data and a normal ambulatory ECG, spirometry and
      echocardiographic analysis, the stress test showed discouraging results. In fact,
      mean work time and peak heart rate were significantly different from normal
      values showing an impaired functional capacity of these children. In conclusion
      we think that bidirectional cavopulmonary anastomosis can not be considered an
      adequate definitive palliation but it represents a very good stage to preserve
      the pulmonary arteries and to prepare the systemic ventricle towards the Fontan
      repair.

PMID- 1383113
TI  - The fenestrated Fontan procedure.
AB  - In 90 patients with characteristics placing them at increased risk for a Fontan
      operation, a fenestration was created in the atrial baffle at the time of the
      Fontan repair. The rational was to allow a right to left shunt which would
      maintain cardiac output and limit right atrial pressure in the presence of
      conditions which limit pulmonary blood flow. Early mortality was 4/90 (4%), with
      an additional two patients having the Fontan repair taken down to a bidirectional
      cavopulmonary anastomosis. Postoperative right atrial pressures were low (average
      13 mm Hg), as was the incidence of prolonged pleural effusions (13%). At short
      term (average 13 months) follow-up, 77% of patients have had closure of the
      fenestration, and 92% are in New York Heart Association Class I. We conclude that
      baffle fenestration with subsequent transcatheter closure results in decreased
      mortality and morbidity among high risk patients undergoing a Fontan repair, and
      that the high functional level at short-term follow-up justifies continued
      aggressive management of such patients.

PMID- 1383114
TI  - Surgical evaluation of the modified Fontan procedure.
AB  - From 1980 to 1990 152 patients underwent Fontan operation at our institution. The
      following patient groups were identified: 1. patients with tricuspid atresia (n =
      82, 54.0%); 2. patients with single ventricle (n = 31, 20.3%); 3. patients with a
      wide variety of non correctable, complex cardiac malformations (n = 39, 25.7%).
      In 27.0% of the patients a primary Fontan operation was performed. 45.0% of the
      patients received a previous shunt to increase pulmonary blood flow and in 29.4%
      of the patients a pulmonary artery band was placed to reduce pulmonary flow.
      Overall mortality was not significantly different in patients with previous
      palliative procedures (19.4%, n = 18) as compared to 17.4% (n = 6) in patients
      with primary Fontan operation. Risk of death was high in the group with complex
      cardiac malformations (28.2%, n = 11) and in patients with single ventricle
      (19.4%, n = 6). Early mortality was considerably less in patients tricuspid
      atresia (8.5%, n = 7). Postoperatively patients with incorporation of the
      residual right ventricular chamber and pulmonary valve (Fontan-Bjoerk) showed a
      significant (p less than 0.05) lower incidence of pleural effusion as compared to
      patients with other modifications of the Fontan procedure. Actuarial survival
      rate of all patients is 83.8 +/- 3.1% (mean +/- SEM) at ten years. The modified
      Fontan procedures are providing an accepted surgical method for patients with
      otherwise non correctable cardiac malformations.

PMID- 1383115
TI  - Hepatitis C viral infection in liver transplant recipients.
AB  - In this study we examined multiple serial liver biopsy specimens from liver
      transplant recipients to determine the pathological features of hepatitis C virus
      induced hepatitis. Hepatitis C virus infections acquired after transplantation
      and previous infections that recurred in patients after transplantation were
      confirmed by the results of the polymerase chain reaction. Of 43 patients
      infected with the hepatitis C virus, 18 had a mild form of chronic hepatitis.
      Four patients had hepatitis that progressed to focal bridging fibrosis or
      cirrhosis. There were no significant clinical or pathological differences between
      infections acquired after transplantation and recurrent infections (as determined
      by polymerase chain reaction) except that acquired infections more often
      developed into hepatitis. Findings indicative of hepatitis C infection included
      portal and parenchymal mononuclear infiltrates of varying degrees, acidophilic
      necrosis and swollen hepatocytes. Other common findings included lymphoid
      aggregates, bile duct damage and fatty change. Atypical pathological conditions
      included extensive hepatocyte swelling or acidophilic necrosis with minimal
      inflammation mimicking ischemia and ductal or ductular damage and proliferation
      with mixed portal infiltrates mimicking rejection or obstruction. We conclude
      that in transplant recipients infection by the hepatitis C virus usually produces
      a mild disease state, but the diagnosis of hepatitis can be difficult to make
      because indicators of hepatitis may mimic those of rejection, ischemia,
      obstruction or other hepatic infections. Serial biopsy specimens with persistent
      pathology and polymerase chain reaction may be necessary to define the presence
      of a hepatitis C virus lesion.

PMID- 1383116
TI  - Hepatitis C virus RNA and antibody response in the clinical course of acute
      hepatitis C virus infection.
AB  - Hepatitis C virus RNA, anti-hepatitis C virus immune response and biochemical
      markers of liver injury were investigated in 17 patients with acute non-A, non-B
      hepatitis. At the first observation, 1 to 3 wk from the clinical onset, all
      patients had hepatitis C virus RNA in their serum, and most (15 of 17) were
      positive for second-generation anti-hepatitis C virus enzyme immunoassay. Follow
      up serum samples were available for 10 patients. The rate of recombinant
      immunoblot assay-confirmed anti-hepatitis C virus enzyme immunoassay reactivities
      increased from 67% in the first 3 wk to 86% after 21 wk. Elevated ALT levels were
      associated with hepatitis C virus RNA positivity in most of cases, but the viral
      nucleic acid was also detected in sera with normal or slightly increased enzyme
      values. None of the single antibodies tested were related to hepatitis C virus
      RNA positivity or to the clinical phase of the infection. Therefore hepatitis C
      virus RNA determination might provide important additional information as
      compared with anti-hepatitis C virus markers, allowing earlier diagnosis,
      discrimination of active infection and, possibly, prognostic evaluation.

PMID- 1383117
TI  - Two distinct subtypes of hepatitis C virus defined by antibodies directed to the
      putative core protein.
AB  - Four distinct genotypes of hepatitis C virus types I, II, III and IV have been
      identified by comparison of nucleotide sequences of isolates from different areas
      of the world. We examined the possibility that hepatitis C virus may have
      serologically definable subtypes. Enzyme-linked immunosorbent assay systems were
      prepared by use of two synthetic peptides deduced from the putative core protein
      of hepatitis C virus. The following are the two peptides that were used: (a)
      IPKARRPEGRTWAQPGY (subtype-1) conserved in hepatitis C virus isolates with type I
      and type II genotypes; and (b) IPKDRRSTGKSWGKPGY (subtype-2) conserved in type
      III and type IV genotypes. With the enzyme-linked immunosorbent assays, the
      subtype-1 antibodies were detected in 26 (68%) of 38 subjects whose hepatitis C
      virus RNA had been genotyped as type I or type II, whereas subtype-2 antibodies
      were not detected. Inversely, the subtype-2 antibodies were detected in 10 (56%)
      of 18 subjects with hepatitis C virus RNA genotypes III or IV, whereas subtype-1
      antibodies were detected in none of them. These results suggest that hepatitis C
      virus has two serologically distinguishable core antigen subtypes, corresponding
      to either genotype I/II or genotype III/IV. Subtyping of HCV by serological
      methods would contribute to tracking transmission routes of the virus, especially
      in cases where serum samples were not stored under conditions to preserve RNA or
      in infected hosts who have cleared the virus and therefore have only antibodies
      remaining to identify the infection.

PMID- 1383118
TI  - Intensive chemotherapy for peripheral T-cell lymphomas.
AB  - Forty-two patients with previously untreated peripheral T-cell lymphomas (PTCL)
      were treated with an intensive chemotherapy protocol. Either the BACOP or the m
      BACOD regimen was used for induction. Patients achieving complete clinical
      remission after three courses were given intensive consolidation and maintenance
      chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan
      Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma.
      There were 27 (64 per cent) males and 15 (36 per cent) females. The median age
      was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I
      disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57
      per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10
      per cent) had bulky disease. According to the Working Formulation, the histology
      was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per
      cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10
      per cent). According to a modified Japanese Lymphoma Study Group's
      classification, the histology in 24 patients (57 per cent) was the pleomorphic
      type, in 13 (31 per cent) immunoblastic-lymphadenopathy-like (IBL-like), and in
      five (12 per cent) unclassifiable. The overall complete remission rate was 67 per
      cent. Twenty-five per cent of the complete responders relapsed and the DFS of the
      CR patients was 62 per cent at three years. The overall survival of all patients
      at three years was 52 per cent. Patients with stage I, II and III disease had
      significantly better CR rate (100 per cent versus 42 per cent, p = 0.001) and
      overall survival (82 per cent versus 35 per cent at three years, p = 0.01) than
      those with stage IV disease but the relapse rate and DFS of CR patients were
      similar. This study shows that the prognosis of patients with PTCL can be
      improved by intensive therapy.

PMID- 1383119
TI  - [Chemistry and immunochemistry analysis of the soluble antigens of newborn larvae
      of Trichinella spiralis].
AB  - The soluble antigens of newborn larvae of Trichinella spiralis were characterized
      in terms of molecular weight of protein, glycoprotein and lipoprotein contents,
      and immunochemistry. After the antigens were separated with SDS-PAGE and then
      followed by ultrasensitive silver staining, at least 40 bands of proteins were
      noted. Correspondingly, 28 bands of glycoproteins and 9 bands of lipoproteins
      were revealed as the similar gels were stained by the hypersensitive periodic
      acid silver and Nile's blue staining respectively. Six specific bands were
      recognized using polyclonal antibodies in the serum of rabbits immunized with
      antigens of newborn larvae by immunoblotting. All of them are glycoproteins. The
      components of the antigens with molecular weight (MW) 41.5 kd, 40 kd, 29.5 kd, 25
      kd, 11 kd and 18 kd were found to be species specific and newborn larva stage
      specific target antigen relevantly.

PMID- 1383120
TI  - [The preparation and identification of anti-idiotypic antibody against Plasmodium
      vivax at erythrocytic stages].
AB  - Through hypotonic dialyzing and gel filtration on Sephadex G200, 6H7G11 McAb-IgM
      (Mouse IgM) was successfully purified. Anti-6H7G11Id (Ab2) was induced in rabbit.
      This Ab2 was identified by agar diffusion, ELISA and competitive assays. The
      results showed that the Ab2 was able to combine respective Ab1 (6H7G11McAb), and
      the binding between Ab2 and Ab1 could be inhibited by Plasmodium vivax (P.v)
      antigen. Meantime, by using Ab2 thus prepared to immunize BALB/c mice, the anti
      6H7G11Id (Ab3 or Ab1') was obtained with specificity of Ab1. It was revealed that
      the Ab2 thus prepared could mimic the antigenic determinant of P.v, and it
      belongs to the cross-reacted idiotype.

PMID- 1383121
TI  - Integrins and their accessory adhesion molecules in mammary carcinomas: loss of
      polarization in poorly differentiated tumors.
AB  - The integrins are alpha beta heterodimeric transmembrane proteins mediating cell
      substratum as well as cell-cell interactions. To identify the pattern of
      expression of the beta 1, beta 3, and beta 4 integrins and their accessory
      adhesion molecules in relation to the malignant phenotype of invasive breast
      cancer, we performed an immunohistochemical study for the alpha 2 beta 1 (VLA-2),
      alpha 6 beta 1 (VLA-6), alpha v and alpha v beta 3 (vitronectin receptor), alpha
      6 beta 4, carcinoembryonic antigen, and carcinoembryonic antigen-related
      molecules in a series of 37 invasive breast carcinomas. All integrin chains
      examined showed similar patterns in nonneoplastic breast tissue, with strong
      membrane staining of the myoepithelial cells and weak to moderate staining on the
      basolateral surfaces of the luminal cells. We found that downregulation of the
      alpha 2 chain of VLA-2 occurs more frequently in poorly differentiated grade III
      invasive ductal carcinomas (IDCs) (P = .048). Loss of alpha 6 beta 4 seems also
      to occur more frequently in grade III IDC (seven of 11 cases, 63.6%) than in
      grade I/II IDC (two of eight cases, 25%), although this did not reach statistical
      significance. Carcinoembryonic antigen and carcinoembryonic antigen-related
      antigens, which are known to function as accessory adhesion molecules, were found
      mainly in the cytoplasm of neoplastic cells and there was reduced membrane
      polarization in poorly organized tumors. In contrast the alpha v beta 3,
      vitronectin receptor heterodimer recognized by the 23C6 monoclonal antibody was
      weak or absent in normal breast epithelium, and was weakly expressed in two of 19
      (10%) IDCs and in nine of 18 (50%) invasive lobular carcinomas (P = .008).
      However, the alpha v chain detected with the antibody 13C2 was weakly to
      moderately expressed on nonneoplastic epithelium and at a similar intensity in 13
      of 19 IDCs and 15 of 17 invasive lobular carcinomas, suggesting that in IDC the
      alpha v chain may be associated with a different beta chain (possibly beta 1 or
      beta 5). No correlation between integrin expression and estrogen/progesterone
      receptor status was found. These data provide further evidence that in invasive
      breast carcinomas there is a widespread deregulated expression of integrins and
      their accessory adhesion molecules with loss of polarization. Changes in the
      expression and function of cell adhesion molecules, which control growth and
      differentiation, may have clinical relevance in the behavior of breast cancer.

PMID- 1383122
TI  - Biochemical characterization of 25 distinct carcinoembryonic antigen (CEA)
      epitopes recognized by 57 monoclonal antibodies and categorized into seven groups
      in terms of domain structure of the CEA molecule.
AB  - The chemical nature of 25 distinct carcinoembryonic antigen (CEA) epitopes, which
      were recognized by 57 different monoclonal antibodies and categorized into 7
      groups (Groups A to G) in terms of domain structure of the CEA molecule, was
      analyzed and the findings obtained were compared with the results of our previous
      studies using recombinant CEA proteins. All 21 epitopes of Groups A to F defined
      by 48 MAbs were resistant to periodate oxidation and were to a greater or lesser
      extent retained after deglycosylation of CEA, indicating that they are all
      protein in nature. The 21 epitopes were detected in recombinant CEA proteins
      expressed in Chinese hamster ovary (CHO) cells. Seven of the 21 epitopes of
      protein nature were partially or completely sensitive to reduction and alkylation
      of CEA and not detected or only slightly revealed in the recombinant CEA proteins
      expressed in E. coli, indicating that those epitopes are dependent on the
      tertiary structure of the peptide chain, which is formed by disulfide bonds. All
      4 epitopes of Group G defined by 9 MAbs were sensitive to mild periodate
      oxidation and deglycosylation, but resistant to reduction and alkylation and to
      digestion with pepsin or pronase, indicating that those 4 epitopes are
      carbohydrate in nature. Although none of the 4 epitopes of Group G were detected
      in the recombinant CEA proteins expressed in E. coli, two were detected in those
      expressed in CHO cells. The biochemical studies reported here thus provide
      information as to the nature of the epitopes on the CEA molecule and help form
      the basis for selecting the anti-CEA MAbs for use in biological study and
      potential clinical applications of CEA.

PMID- 1383123
TI  - Production and characterization of four anti-neuropeptide Y monoclonal
      antibodies.
AB  - Human neuropeptide Y (hNPY) is a potent vasoconstrictor peptide of 36 aminoacid
      residues. We isolated hybridomas secreting four monoclonal antibodies directed
      against various epitopes of neuropeptide Y and studied their cross-reactivity
      with peptide YY (PYY) and the pancreatic polypeptide (PP), two peptides sharing
      sequence homologies with hNPY (respectively 70% and 50%). The antibody NPY02 is
      an IgG1 with a Ka of 5.5 x 10(10) liters/mol. It binds to the 11-24 region of NPY
      (IC50 = 2 x 10(-7)M), does not recognize PP but cross-reacts weakly with PYY.
      Antibodies NPY03 and NPY05 are IgG2 with respective Ka's of 6.7 x 10(9) and 2.5 x
      10(10) liters/mol. They interact with a C-terminal epitope on NPY (NPY 27-34,
      IC50 = 2 x 10(-9) M for NPY03 and NPY 32-36, IC50 = 1 x 10(-9) M for NPY05).
      These two antibodies cross-react with PYY whereas only NPY05 binds PP. NPY05 is
      unable to bind the free acid form of neuropeptide Y. The 32-36 COOH free
      subpeptide is recognized 50,000 less efficiently by NPY05 than its amidated form.
      Antibody NPY04 is an IgG3 with a Ka of 3.8 x 10(8) liters/mol. It recognizes a N
      terminal epitope between aminoacids 1 and 12 (IC50 = 2.5 x 10(-6) M). NPY04
      interacts weakly with PYY but not detectably with PP. These results obtained with
      4 different monoclonal antibodies demonstrate the presence of at least four
      epitopes on hNPY, two of them being continuous. These antibodies will be used to
      study the interaction of NPY with its receptor and to develop sensitive and
      specific assays for determination of NPY concentrations in biological fluids.

PMID- 1383125
TI  - Antibodies raised against peptide fragments of CD16 reacting with membrane and
      soluble form of CD16. I: Production and characterization.
AB  - Monoclonal antibodies (MAbs) were generated against human CD16 (Fc gamma RIII) by
      fusion of NS1 myeloma cells with spleen cells from BALB/c mice immunized with
      synthetic peptide sequences derived from the CD16 genes. After screening, four
      hybridomas secreting MAbs (2 IgM and 2 IgG) were selected, cloned and
      characterized for their activity against CD16 by ELISA test, flow cytometry,
      rosette inhibition and immuno-blotting. MAbs reacted strongly in ELISA with a
      soluble form of CD16 (sCD16) present in human serum and to a lesser degree with
      soluble recombinant CD16 (srCD16). The binding characteristics of the four
      antibodies to the sCD16 were different, implying that the antibodies recognize
      different CD16 epitopes. FACS analysis of peripheral blood from healthy
      volunteers demonstrated that these MAbs are highly reactive with membrane CD16 of
      neutrophils cells (70-95%) and with a subset of lymphocytes (6-14%). These MAbs
      seem interesting and may lead to the purification of the soluble human CD16 and
      to the knowledge of its functions, its physiological role and the cellular
      polymorphism.

PMID- 1383124
TI  - Production and characterization of a monoclonal antibody against the ribosome
      inactivating protein alpha sarcin.
AB  - In order to improve the purification of immunoconjugates containing alpha sarcin,
      a ribosome-inactivating protein, and in the attempt to define the enzymic region
      of the toxin, MAbs against alpha sarcin were produced. From 5 fusions, by
      adopting a short period of immunization and very low doses of the immunogen, 10
      anti-toxin-producing clones were obtained. One of them, named MAsg2 (IgG2b), due
      to its specific reactivity and secreting properties, was selected for further
      characterization. MAsg2 was found to recognize an epitope which is common to two,
      i.e. alpha sarcin and clavatin, of the three different aspergillins tested, but
      is not involved in the active site of the toxins.

PMID- 1383126
TI  - Purification of MPB70 and production of specific monoclonal antibodies.
AB  - MPB70 is a protein secreted into the culture filtrate of Mycobacterium bovis BCG
      (substrain Tokyo 172), which is able to induce a delayed-type hypersensitivity
      (DTH) skin reaction in guinea pigs immunized with BCG-Tokyo. By high-pressure
      chromatofocusing and size-exclusion high performance liquid chromatography, a
      further purified MPB70 protein was obtained, which was visualized as a single
      band with a molecular mass of 22 kDa by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis. A series of hybridoma cell lines that produced monoclonal
      antibodies (MAbs) against the purified MPB70 protein was prepared, and three
      MAbs, Bov-1, Bov-2, and Bov-3, with strong antigen-binding capacities were
      established. Bov-1 was the most potent MAb among them and binds to only a 22 kDa
      protein band in culture filtrates of M. bovis, but not to bands in those of M.
      tuberculosis by Western immunoblotting analysis, suggesting that Bov-1 recognize
      different epitope of MPB70 from MAbs that have been shown previously to recognize
      several species of molecules in culture filtrates of M. bovis. The purified MPB70
      protein elicited a strong DTH skin reaction in guinea pigs sensitized with BCG
      Tokyo vaccine. Bov-1 had no inhibitory effect on generation of the DTH skin
      reaction, showing that MAb bound to an epitope distinct from that inducing the
      skin reaction. All of the three MAbs were specific to MPB70 and each recognized a
      different epitope on MPB70. MPB70 was not detected in the culture filtrate of M.
      tuberculosis H37Rv. Thus, these MAbs may be useful for detecting MPB70 in studies
      on discriminating infection with M. bovis in domestic animals or in
      distinguishing vaccination with BCG-Tokyo from other mycobacterial infections in
      humans.

PMID- 1383128
TI  - Production and characterization of murine mAbs to the extracellular domain of
      human neu oncogene product GP185HER2.
AB  - The oncogene HER-2/neu encodes a transmembrane glycoprotein of 185 kDa (gp185HER
      2) with tyrosine-kinase activity. Gene amplification and high levels of
      expression of gp185HER-2 have been found to correlate with poor clinical outcome
      in breast and ovarian carcinomas. Employing a somatic cell hybrid fusion
      protocol, which yields a high frequency production of hybridomas, we have
      analyzed the extent of the murine immune response to the gp 185 extracellular
      domain. In a single fusion experiment, using as immunogen NIH 3T3 cells
      expressing high levels of a transfected human HER-2 gene, we have generated mAbs,
      mainly of IgG1 isotype, displaying high affinity (10(7)-10(10) mol/L) to gp 185.
      Analysis of the epitope specificity has allowed the identification of five
      distinct groups of spatially related epitopes, each provided with different
      immunodominancy, and all resistant to formalin fixation. The use of inhibitor of
      N-linked glycosylation tunicamicyn has demonstrated that the mAbs bind to
      epitopes localized in the protein core of gp185HER-2. Because recent reports have
      shown that gp185HER-2 has a restricted expression in normal tissues and is
      homogenously detectable in metastatic foci of gp 185 + primary tumors, antibodies
      to this macromolecule, in addition to their prognostic value, may represent
      reagents for in vitro and in vivo diagnostic applications, as well as for the
      development of therapeutic strategies.

PMID- 1383127
TI  - Monoclonal antibodies to the human multicatalytic proteinase (proteasome).
AB  - Multicatalytic proteinase is an intracellular enzyme composed of at least 12
      different subunits. Seven murine hybridoma cell lines secreting antibodies to
      human multicatalytic proteinase (MCP) were established. The antibodies reacted
      with 4 different subunits of the oligomeric protein. Three of the antibodies
      bound to identical or closely spaced epitopes on the largest subunit, as shown by
      binding competition. Some of the antibodies cross-reacted with MCP from rat or
      rabbit, but none with lobster MCP. Glycoprotein components could not be detected
      in human MCP. The monoclonal antibodies and two polyclonal rabbit antibodies did
      not specifically inhibit the enzymatic activity of human MCP. Electrophoretic
      analysis of MCP immunoprecipitated from human placenta, liver, kidney, or HeLa
      cell extracts with antibodies to 3 different subunits suggested that the subunit
      compositions are very similar or identical.

PMID- 1383129
TI  - The nature of the unhydrolysed fraction of alpha-globulin, the major protein
      component of Sesamum indicum L. hydrolysed by alpha-chymotrypsin.
AB  - Alpha-globulin, the high molecular weight protein fraction from sesame (Sesamum
      indicum L.) seed, was hydrolysed by alpha-chymotrypsin. The hydrolysate was
      resolved into two fractions, the hydrolysed part and the unhydrolysed part of
      alpha-globulin using gel filtration on Sepharose 6B-100. The unhydrolysed alpha
      globulin residue was characterized for its sedimentation coefficient, subunit
      composition, fluorescence emission spectrum, secondary structure, and other
      biophysical properties. The results indicated a decrease in the size of the
      protein molecule upon hydrolysis to a very small extent. The effect of hydrolysis
      products on hydrolysis of native alpha-globulin as well as on a standard
      substrate, casein, was also investigated. The results indicated that the
      hydrolysis products contribute to the resistance of alpha-globulin to proteolysis
      by alpha-chymotrypsin to the extent of 40%.

PMID- 1383130
TI  - Further studies on proteinases and alpha 2-macroglobulin activity in diabetic
      plasma.
AB  - Loss of chymotrypsin binding capacity of alpha 2-macroglobulin in diabetic plasma
      on in vitro incubation, could be partially prevented by phenylmethyl sulphonyl
      fluoride and pepstatin A. Prior ten-fold dilution of plasma with 0.02 M phosphate
      buffer (pH 7.0) completely arrested the process. The phenomenon could not be
      reactivated by Ca2+, lecithin or bovine serum albumin. Diabetic plasma, like
      normal plasma, exhibited maximal hydrolytic activities on H-D-Pro-Phe-Arg-p
      nitroanilide, H-D-Val-Leu-Arg-p-nitroanilide and H-D-Ile-Pro-Arg-p-nitroanilide.
      The hydrolytic activities were not significantly diminished on incubation of
      plasma at 37 degrees C for 12 hr, unlike alpha 2-macroglobulin activity. On gel
      chromatography on Sephadex G-200, part of the proteolytic activity in diabetic
      plasma coeluted with alpha 2-macroglobulin in the VO region. A second activity
      peak (absent in normal plasma) was eluted with a Ve/V0 value of 1.40. Possible
      role of free proteinases in diabetic plasma in the inactivation of alpha 2
      macroglobulin is discussed.

PMID- 1383132
TI  - Characterization of the membrane attack complex inhibitory protein CD59 antigen
      on human amniotic cells and in amniotic fluid.
AB  - A functional complement system and the potential for its activation are present
      in human amniotic fluid. We have recently demonstrated that CD59 antigen is
      present and functionally active on human amniotic epithelial cells (HAEC). We
      have now further examined the role of this protein on HAEC and have also
      demonstrated its presence in amniotic fluid (AF). CD59 Ag on HAEC is similar in
      size to the erythrocyte protein and is anchored via glycosyl
      phosphatidylinositol. The AF protein retained the capacity to incorporate into
      target cells and protect against lysis by complement. These data suggest that
      HAEC secrete into AF a form of CD59 Ag which retains inhibitory activity and
      which may be important in protection of the foetus from maternal complement in
      utero.

PMID- 1383133
TI  - Interleukin-4 suppresses granulocyte colony-stimulating factor and granulocyte
      macrophage colony-stimulating factor levels in stimulated human monocytes.
AB  - Granulocyte colony-stimulating factor (G-CSF) was quantitated in the supernatants
      of lipopolysaccharide (LPS)-treated human monocytes by ELISA. Unlike previous
      reports, the lymphokines, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma),
      were unable to induce the synthesis of G-CSF. Both IL-4 (> or = 10 pM) and the
      glucocorticoid, dexamethasone (10(-7) M), inhibited G-CSF production in the LPS
      treated monocytes; in contrast, IFN-gamma had a weak potentiating effect on the
      LPS action. Changes in antigen expression were manifested at the level of
      messenger RNA (mRNA). Granulocyte-macrophage (GM)-CSF in the LPS-treated monocyte
      supernatants was also quantitated by ELISA but its levels were somewhat lower
      than for G-CSF; IL-4, dexamethasone and IFN-gamma had similar effects on GM-CSF
      levels as on G-CSF levels. The suppression of CSF production in the stimulated
      monocytes by IL-4 and glucocorticoid extends the list of monocyte cytokines whose
      levels can be down-regulated by these agents and suggests another potential anti
      inflammatory and immunosuppressive function for IL-4.

PMID- 1383135
TI  - Functional localization of an exocytosis-triggering G-protein in human cytotoxic
      T lymphocytes.
AB  - Human cloned CD8+ cytotoxic T lymphocytes permeabilized with alpha-toxin of
      Staphylococcus aureus can be triggered by the guanosine triphosphate (GTP)
      analogue GTP gamma S to release the contents of their granula by exocytosis. To
      localize the guanosine nucleotide-binding protein (G-protein) activated by GTP
      gamma S in the sequence of events after T-lymphocyte triggering we have used
      several inhibitors of T-cell activation that inhibit early stages in T-cell
      triggering. The protein kinase C-inhibitor staurosporine, the immunosuppressants
      cyclosporin A and FK-506 and genistein, an inhibitor of tyrosine kinases, all
      inhibited esterase release triggered in intact cells by anti-T-cell receptor
      antibodies but not GTP gamma S-induced release from permeabilized cells.
      Cyclosporin A, FK-506 and genistein also blocked exocytosis triggered in intact
      cells by a combination of phorbolester and the calcium ionophore A23187. In
      addition, cytochalasin B, an inhibitor of actin polymerization, inhibited
      exocytosis in intact cells but enhanced exocytosis from permeabilized cells.
      These data show that the G-protein effecting exocytosis is localized distally in
      the cascade of events after T-cell activation.

PMID- 1383134
TI  - Bypass of carrier-induced epitope-specific suppression using a T-helper epitope.
AB  - A gonadotropin-releasing hormone (GnRH)-based vaccine is being developed as a
      method for non-surgical immunotherapy as immunization with this vaccine results
      in atrophy of the prostate. This vaccine, a conjugate of GnRH and diphtheria
      toxoid (DT), provides a unique hapten-carrier system for investigating the
      influence of carrier presensitization on antibody responses to self haptens. In a
      recent communication we showed that preimmunization with carriers diphtheria
      toxoid and tetanus toxoid results in a strain-dependent inhibition of anti-GnRH
      responses in mice and that T cells from carrier-presensitized mice are
      responsible for anti-haptenic suppression. In the present report we describe a
      strategy for bypassing DT-induced epitopic suppression using a T-helper epitope
      from DT.

PMID- 1383136
TI  - A ligand-epitope in vitro analysis of major histocompatibility determinants
      expressed on B and T lymphocytes.
AB  - Human histocompatibility leucocyte antigen (HLA)-specific monoclonal antibody
      probes were used to determine the affinity constant, and cell-surface density of
      HLA class I and class II determinants. The measurements were estimated for single
      cell units of B-lymphoblastoid cell line (B-LCL) and cloned activated T cells in
      different functional states. Each HLA subset showed unimodal affinity constant
      values for the interaction with the corresponding HLA-specific antibodies. Such
      values ranged between 2.2 x 10(7) M-1 (class I) and 4.0 x 10(7) M-1 (class II)
      for different histocompatibility epitopes. In both B and T cells there was a rank
      order of epitope expression, class I being highly expressed (5 x 10(6)
      epitopes/cell) followed by DR, DQ and DP, (1.1-3.0 x 10(6) epitopes/cell).
      Suppressive clones carrying functionally defined stimulating determinants
      previously designated 'DY' carried similar numbers of DR, DQ and DP binding sites
      to DY- non-suppressive clones, but showed selective increases of class II
      determinants reactive with broad class II-specific antibodies. The results are
      discussed in the context of the functional consequences of different patterns of
      HLA epitope expression in immune responses.

PMID- 1383137
TI  - T-cell receptor-gamma delta association with lymphocyte populations in sheep
      intestinal mucosa.
AB  - T cells expressing T-cell receptor (TcR)-gamma delta and CD8 represent a
      significant population in mouse and chicken intra-epithelial lymphocytes (IEL)
      but represent a minor population in human IEL. We examined the TcR-gamma delta
      usage and co-expression of CD5, CD4, CD8 and major histocompatibility complex
      (MHC) class II on isolated sheep IEL and lamina propria lymphocytes (LPL), and
      compared them with the TcR-gamma delta + cells in peripheral blood, intestinal
      lymph and jejunal Peyer's patches (PP). There were a number of notable
      differences. TcR-gamma delta + cells comprised 18% of IEL and 10% of LPL. Among
      the population of TcR-gamma delta + IEL, 24% were CD8+ and 54% were CD5+, which
      contrasts with the TcR-gamma delta + cells in blood and intestinal lymph that
      were universally CD5+ CD4- CD8-. A notable feature of the IEL was the presence of
      distinct CD8+ and TcR-gamma delta + populations that lacked CD5. Also a high
      percentage of IEL and LPL were CD2+ and MHC class II+. Analysis of the expression
      of MHC class II on T-cell subsets, as an indicator of activation, showed that 60
      95% of the various IEL and LPL subsets were MHC class II+ compared with only 5
      40% in jejunal PP, lymph nodes, spleen and blood. Therefore, it is possible that
      the circulating TcR-gamma delta + and CD8+ cells that localize in the gut
      epithelium might become activated and stop the expression of CD5 under the
      influence of the local microenvironment. These cells appear not to emigrate while
      still expressing the TcR-gamma delta + (CD8+) CD5- MHC class II+ phenotype. Our
      data, together with those from other studies, show that there is much
      heterogeneity in the use of TcR-gamma delta and accessory T-cell molecules by
      IEL.

PMID- 1383139
TI  - A and B antigenicity of human spermatozoa and buccal epithelial cells.
AB  - The source of A and B antigens on the surface of erythrocytes, spermatozoa and
      buccal epithelial cells was studied using two kinds of monoclonal antibodies of
      differing specificity. The first, anti-Ar, reacts with the erythrocyte A antigen
      but not with the soluble A antigen found in secretions such as saliva. Similarly,
      anti-Br reacts with the erythrocyte B antigen but not with the soluble B antigen
      present in secretions. The second type of monoclonal antibody, anti-Ar+s, reacts
      with both the erythrocyte A antigen and with the soluble A blood group substance.
      Similarly, the anti-Br+s reacts with both the erythrocyte B antigen and with the
      soluble B blood group substance. The spermatozoal A antigen reacts only with the
      anti-Ar+s monoclonal antibody whereas buccal epithelial A antigen reacts with
      both anti-Ar and with anti-Ar+s. Spermatozoal B antigen reacts only with anti
      Br+s whereas buccal epithelial B antigen reacts with both anti-Br and anti-Br+s.
      Buccal cell a and B antigens appear to be integral to the membrane or at least
      tightly bound whereas the spermatozoal A and B antigens are adsorbed from seminal
      plasma and loosely bound.

PMID- 1383138
TI  - Inhibition of programmed cell death by cyclosporin A; preferential blocking of
      cell death induced by signals via TCR/CD3 complex and its mode of action.
AB  - Cyclosporin A (CsA) is reported to inhibit programmed cell death. We confirmed
      this by using T-cell hybridomas which are inducible to programmed cell death by
      activation with immobilized anti-CD3 antibody or with anti-Thy 1.2 antibody. Cell
      death and DNA fragmentation, characteristic features of programmed cell death,
      were almost completely blocked by CsA or FK506. To investigate whether CsA
      inhibits only the cell death through the signals via the TCR/CD3 complex or all
      of the programmed cell death induced by various reagents, we further established
      CD4+8+ thymic lymphomas which result in programmed cell death after activation
      with calcium ionophore, dexamethasone, cyclic AMP or anti-CD3 antibody. It was
      revealed that CsA could block only the cell death mediated by the TCR/CD3
      complex. For the clarification of the site of action of CsA, Ca2+ influx and
      endocytosis of receptors after stimulation with anti-CD3 antibody were monitored
      in the presence of CsA, and no significant effects of CsA were observed.
      Furthermore, prevention of cell death was examined by adding CsA at various
      periods of time after initiation of culture. CsA was found to exert its effect
      even when added after 4 h of cultivation, and the kinetic pattern of suppression
      was similar to that of the suppressive effect on IL-2 production. These
      observations indicate that in the events of programmed cell death, the major site
      of action of CsA will not be the inhibition of the immediate membrane events
      after activation of the TCR/CD3 complex but rather the interference in the
      function of molecules that transmit signals between membrane events and the
      activation of genes in the nucleus.

PMID- 1383140
TI  - Role of endoscopic ambulatory laser therapy in palliation of malignant colorectal
      diseases.
AB  - BACKGROUND: Endoscopic laser therapy is widely used in the palliation of advanced
      malignant colorectal diseases. The role of this therapy in improving the quality
      of life of these patients needs adequate assessment. METHODS: Nine patients with
      advanced colorectal cancers and three patients with secondary colorectal
      involvement by pelvic cancers underwent endoscopic Nd:YAG laser therapy for
      palliation using non-contact laser guides for tumor bleeding alone (n = 12) or
      associated with obstruction (n = 7). The therapy was performed on an outpatient
      basis in 9 of the 12 patients. One patient was lost to follow up. RESULTS:
      Symptom control was achieved in all the 11 bleeding tumors and in 5 of the 7
      obstructive tumors. There were no major complications. Three patients had no
      improvement in the quality of life in spite of control of symptoms. CONCLUSION:
      Ambulatory endoscopic laser therapy is a minimally invasive, safe and effective
      method of palliation for selected patients with non-resectable malignant
      colorectal tumors.

PMID- 1383131
TI  - Cellular and humoral antigenic epitopes in HIV and SIV.

PMID- 1383142
TI  - Child development: pre-screening, screening and super-screening.

PMID- 1383141
TI  - Hepatitis C virus infection in chronic liver disease in Bombay.
AB  - To find out the prevalence of antibody of hepatitis C virus (anti-HCV) in
      patients with chronic liver disease in Bombay, sera from 126 patients (93 men, 33
      women; aged 9-70 years, mean 39.7) with chronic liver disease (cirrhosis 103,
      cirrhosis with hepatocellular carcinoma 3, chronic active hepatitis 20) were
      tested for HBsAg and anti-HCV antibody. HBsAg positive sera were tested for anti
      delta antibody and IgM anti-HBc. All the tests were carried out by ELISA. Of 126
      patients, 51 (40.5%) were HBsAg positive, 49 (38.8%) alcoholic and 21 (16.6%)
      anti-HCV positive. The prevalence of anti-HCV in HBsAg positive, alcoholic and
      cryptogenic (HBV negative and no alcohol) liver disease patients was 13.7%, 14.7%
      and 20.5% respectively. Of 21 anti-HCV antibody positive patients, 8 (38%) had
      received blood transfusions previously. HCV is present in 15-20% of patients with
      chronic liver disease in Bombay.

PMID- 1383144
TI  - The adverse effect of marginally higher lead level on intelligence development of
      children: a Shanghai study.
AB  - We surveyed 128 preschool children in a lead-polluted area in Shanghai to study
      the relationship between blood lead level and neuropsychological functions,
      assessed by age-appropriate psychological tests. The geometric means of blood
      lead level was 21.7 + -10.8 micrograms/dl. Of 47 children aged below 30 months,
      there was no significant difference in BSID indices between the high and low lead
      subjects, although the high lead children tended to have poorer development
      scores than the low lead ones. On the other hand, of 81 children older than 46
      months, the WPPSI IQ scores showed highly significant negative correlation with
      blood lead level. Step-wise regression and multiple analysis of covariance
      techniques were employed to find out and control the confounding factors. Even
      when 21 non-lead variables were considered, the IQ difference between high and
      low lead groups remained statistically significant. We concluded that the
      children, especially those older than 46 months, in the area investigated, did
      suffer from lead toxicity causing impairment in intelligence development. We
      support the view that marginally higher lead level in children should be taken
      seriously.

PMID- 1383143
TI  - Protein energy malnutrition (PEM), brain and various facets of child development.
AB  - Protein energy malnutrition (PEM) is a global problem. Nearly 150 million
      children under 5 years in the world and 70-80 million in India suffer from PEM,
      nearly 20 million in the world and 4 million in India suffer from severe forms of
      PEM, viz., marasmus, kwashiorkor and marasmic kwashiorkor. The studies in
      experimental animals in the west and children in developing countries have
      revealed the adverse effects of PEM on the biochemistry of developing brain which
      leads to tissue damage and tissue contents, growth arrest, developmental
      differentiation, myelination, reduction of synapses, synaptic transmitters and
      overall development of dendritic activity. Many of these adverse effects have
      been described in children in clinical data, biochemical studies, reduction in
      brain size, histology of the spinal cord, quantitative studies and electron
      microscopy of sural nerve, neuro -CT scan, magnetic resonance imaging (MRI) and
      morphological changes in the cerebellar cells. Longer the PEM, younger the child,
      poorer the maternal health and literacy, more adverse are the effects of PEM on
      the nervous system. Just like the importance of nutrients on the developing
      brain, so are the adverse effects on the child development of lack of
      environmental stimulation, emotional support and love and affection to the child.
      When both the adverse factors are combined, the impact is severe. Hence
      prevention of PEM in pregnant and lactating mothers, breast feeding, adequate
      home based supplements, family support and love will improve the physical growth,
      mental development, social competence and academic performance of the child.
      Hence nutritional rehabilitation, psychosocial and psychomotor development of the
      child should begin in infancy and continue throughout. It should be at all
      levels, most important being in family, school, community and various
      intervention programmes, local, regional and national. Moreover medical students,
      health personnel, all medical disciplines concerned with total health care and
      school teachers should learn and concentrate on the developmental stimulation and
      enrichment of the child.

PMID- 1383146
TI  - Structural identification of an epitope of antigenic factor 5 in mannans of
      Candida albicans NIH B-792 (serotype B) and J-1012 (serotype A) as beta-1,2
      linked oligomannosyl residues.
AB  - In previous articles, we reported the presence of phosphate-bound beta-1,2-linked
      oligomannosyl residues in the mannans of strains of Candida albicans serotypes A
      and B and Candida stellatoidea. To identify the antigenic factor corresponding to
      this type of oligomannosyl residue, a relationship between chemical structure and
      antigenic specificity in the mannans of C. albicans NIH B-792 (serotype B, B
      strain) and C. albicans J-1012 (serotype A, J-strain) was investigated by using a
      combination of two-dimensional 1H nuclear magnetic resonance spectroscopy of H-1,
      H-2, and H-5 regions in the mannans and an enzyme-linked immunosorbent assay that
      employed concanavalin A-coated microtiter plates. It was shown in the present 1H
      nuclear magnetic resonance study that an examination of chemical shifts not only
      in the H-1 region but also in the H-5 region was useful for the quantitative
      determination of the phosphate-bound beta-1,2-linked oligomannosyl residues. In
      the enzyme-linked immunosorbent assay using concanavalin A-coated plates, it was
      revealed that, of factor sera 1, 4, and 5, only factor serum 5 showed a
      reactivity proportional to the densities of the beta-1,2-linked oligomannosyl
      residues of the mannan subfractions of different phosphate contents that had been
      prepared from the bulk B-strain mannan by DEAE-Sephadex chromatography. The above
      results indicate that the phosphate-bound beta-1,2-linked oligomannosyl residues,
      Manp beta 1----(2Manp beta 1----)n2Man (n = 0-5), correspond to antigenic factor
      5.

PMID- 1383145
TI  - Identification of human T-cell epitopes on the S4 subunit of pertussis toxin.
AB  - Ten adult humans were vaccinated with the Japanese acellular pertussis vaccine
      JNIH-3, containing detoxified pertussis toxin (PT), formaldehyde, and filamentous
      hemagglutinin. The vaccination induced a specific antibody response to PT and
      filamentous hemagglutinin, and a Western blot (immunoblot) analysis of the
      antibody response to PT revealed antibodies to PT subunits S1, S2, S3, S4 and S5.
      The response of peripheral lymphocytes to PT was assessed in an in vitro
      proliferation assay. A proliferative response to detoxified PT and PT dimers S2
      S4 and S3-S4 was found, and it was further demonstrated that the proliferative
      response to detoxified PT and dimer S2-S4 was mediated by T cells of the CD4+
      phenotype. The specificity of the proliferative response to subunit S4 was
      analyzed with a range of synthetic peptides synthesized on the basis of the
      primary sequence of subunit S4. The proliferative response to the peptides
      revealed two major and one minor T-cell epitope located in the NH2-terminal end
      of subunit S4.

PMID- 1383147
TI  - Differential effects of monoclonal antibodies to tumor necrosis factor alpha and
      gamma interferon on induction of hepatic nitric oxide synthase in experimental
      gram-negative sepsis.
AB  - To investigate the stimuli required for the induction of nitric oxide synthase
      (NOS) in sepsis, we have analyzed the levels of this enzyme in the livers of mice
      infected with a 90% lethal dose of Escherichia coli in a model of gram-negative
      sepsis. Hepatic NOS levels are markedly induced in this model, with peak values
      occurring 12 to 22 h following infection. Treatment with TN3-19.12, a
      neutralizing monoclonal antibody to tumor necrosis factor alpha (TNF-alpha),
      resulted in complete protection from death in this model of sepsis but had no
      significant effect on the level of induction of hepatic NOS. Treatment with H22,
      a monoclonal antibody to gamma interferon (IFN-gamma), also gave significant
      protection against death and, in addition, did lead to a decrease in the level of
      induction of the hepatic NOS. Treatment of mice with pure TNF-alpha (0.2
      microgram), IFN-gamma (2,000 U), or a combination of the two did not induce the
      hepatic NOS, but treatment with the combination led to significant mortality
      (probability of survival at 22 h, 0.32). Thus, the level of induction of NOS
      within the liver either in sepsis or by the coadministration of TNF-alpha and IFN
      gamma does not correlate with death.

PMID- 1383149
TI  - Bovine helper T cell clones recognize five distinct epitopes on Babesia bovis
      merozoite antigens.
AB  - Helper T cell clones from two Babesia bovis-immune cattle were characterized for
      use in identification of potentially protective immunogens of B. bovis
      merozoites. Proliferation assays with 11 CD4+ clones revealed a differential
      pattern of response to soluble cytosolic antigen, membrane-enriched antigen,
      detergent extracts of the membrane-enriched antigen, soluble culture supernatant
      exoantigen, and different geographical isolates of B. bovis as well as Babesia
      bigemina parasites. When the data were combined, the clones could be grouped
      according to five different patterns of response. One group recognized only the
      membrane-enriched fraction of New World and Australian parasites. Four remaining
      groups recognized antigens found in the cytosolic as well as the membrane
      enriched fraction, and clones representative of each group were used to identify
      cytosolic antigens fractionated by anion-exchange chromatography with the use of
      fast-performance liquid chromatography. One clone (C97.3C3), which responded to
      all B. bovis isolates and to B. bigemina, recognized a single peak of activity
      that eluted with 0.25 M NaCl and contained protein bands of 70 and 75 kDa. The
      remaining clones were stimulated by a second antigenic peak that eluted between
      0.35 and 0.45 M NaCl and contained protein bands of 42, 47, 56, and 84 kDa. The
      majority of the clones produced interferon, whereas tumor necrosis factor
      alpha/tumor necrosis factor beta production was less frequent. These studies
      provide the basis for using helper T cell clones to identify potentially
      protective immunogens of B. bovis and delineate a minimum of five helper T cell
      epitopes recognized by two immune cattle.

PMID- 1383148
TI  - WI-1, a novel 120-kilodalton surface protein on Blastomyces dermatitidis yeast
      cells, is a target antigen of cell-mediated immunity in human blastomycosis.
AB  - A large body of experimental data has demonstrated the central role of T cells in
      acquired resistance to the dimorphic fungus Blastomyces dermatitidis. We examined
      the human T-cell response to WI-1, a 120-kDa B. dermatitidis yeast cell surface
      protein recently shown to be an immunodominant antigen of the B-cell response in
      infected humans. Peripheral blood lymphocytes from 10 blastomycosis patients
      studied proliferated in response to WI-1 (mean, 19,431 cpm) and to the standard,
      crude cell wall antigen, Blastomyces alkali- and water-soluble antigen (B-ASWS)
      (mean, 19,131 cpm); lymphocytes from 10 histoplasmosis patients and 10 normal
      control subjects did not respond to WI-1. WI-1 stimulation of patient lymphocytes
      and rechallenge with WI-1 or B-ASWS showed that the antigens share immunodominant
      epitopes. Of 100 WI-1-responsive T-cell clones derived from peripheral blood, 10
      were studied in detail to assess the phenotype, function, and ligands recognized.
      The clones exhibit the CD3+ CD4+ phenotype of helper T cells; 2 of 10 clones (and
      21% of antigen-stimulated peripheral blood lymphocytes) use the V beta 8 T-cell
      receptor gene element to respond to WI-1. All the clones proliferate in response
      to both WI-1 and B-ASWS but not other fungal antigens, and some mediate potent
      cytolytic effects on WI-1- and B-ASWS-labeled targets. WI-1 recognition requires
      antigen processing and presentation of epitopes in association with HLA-DR (to
      noncytolytic clones) and HLA-DP (to cytolytic clones). From these findings, we
      conclude that CD4+ T cells with regulatory and cytolytic properties are involved
      in the development of acquired resistance of B. dermatitidis, that the cells are
      directed against WI-1, and that the manner of display of WI-1 peptide epitopes in
      conjunction with major histocompatibility complex class II may influence the
      profile of the immune response.

PMID- 1383150
TI  - Cytoadherence characteristics of rosette-forming Plasmodium falciparum.
AB  - Sequestration of Plasmodium falciparum-infected erythrocytes to the capillary
      endothelium can cause obstruction and localized tissue damage. Occlusion of
      vessels in falciparum malaria infection has been related to two properties of the
      parasite: adhesion to endothelial cells and rosette formation. Our study on P.
      falciparum isolates from Thailand producing variable numbers of rosettes suggests
      the involvement of rosettes in capillary blockage caused by direct adhesion of
      the rosette-forming infected erythrocytes to various target cells, e.g., live
      human umbilical vein endothelial cells, monocytes, and platelets. These rosettes
      did not bind Formalin-fixed target cells, nor did they bind to live or fixed C32
      or G361 melanoma cells. Classification of the receptors involved in cytoadherence
      of endothelial cells and monocytes by specific antibody blocking and flow
      cytometry indicated that CD36 was involved in the adherence of monocytes but that
      other receptors besides CD36 may be involved in parasite adherence to endothelial
      cells. The cytoadherence of infected erythrocytes to monocytes was also
      associated with CD54 (ICAM-1). Further, differentiation of adherent monocytes
      resulted in an inversion of CD36 and CD54 levels on the cell surface which
      correlated with a decrease in surface binding of infected erythrocytes. This
      observation suggests that the state of cell activation and differentiation may
      also contribute to sequestration of parasites and to the pathogenesis of malaria.

PMID- 1383151
TI  - Identification and characterization of epitopes shared between the mycobacterial
      65-kilodalton heat shock protein and the actively secreted antigen 85 complex:
      their in situ expression on the cell wall surface of Mycobacterium leprae.
AB  - Both mycobacterial hsp65 and the actively secreted antigen 85 complex of 30-kDa
      region proteins are considered to be major immune targets in mycobacterial
      diseases. In this study, by using a novel series of monoclonal antibodies (MAbs)
      directed to these antigens, we identified and partially characterized three
      unique epitopes (Rb2, Pe12, and A2h11) that are shared between mycobacterial
      hsp65 and the individual components of the antigen 85 complex. Dot blot assays
      with native purified proteins revealed that all three MAbs are strongly bound to
      hsp65 and antigens 85A (MPT44) and 85B (MPT59), while a weak reaction or no
      reaction was found with antigen 85C (MPT45). Immunoblotting showed that MAb Rb2
      reacted strongly with both hsp65 and the antigen 85 complex proteins, whereas
      MAbs Pe12 and A2h11 reacted strongly with the former but weakly with the latter.
      Moreover, these MAbs did not react with other closely related MPT51 and MPT64
      secreted proteins. Further characterization of these epitopes was performed by
      using recombinant fusion and truncated proteins of Mycobacterium bovis BCG hsp65
      (MbaA) and the M. leprae 30- and 31-kDa antigen 85 complex fusion proteins. In
      hsp65, Rb2-Pe12- and A2h11-reactive epitopes were found to reside in the C
      terminal region of amino acid residues 479 to 540 and 303 to 424, respectively.
      In the M. leprae 30- and 31-kDa antigen 85 complex, all three epitopes were
      located in an N-terminal region of amino acid residues 55 to 266, one of the
      known fibronectin-binding sites of the M. leprae antigen 85 complex. Comparison
      of these MAb-reactive amino acid sequence regions between mycobacterial hsp65 and
      the components of the antigen 85 complex revealed that these regions show certain
      amino acid sequence identities. Furthermore, by immunoperoxidase and immunogold
      ultracytochemistry, we demonstrated that Rb2-, Pe12-, and A2h11-reactive epitopes
      are expressed both on the cell wall surface and in the cytosol of M. leprae
      bacilli within the lesions of lepromatous leprosy patients and in M. leprae
      infected armadillo liver tissue.

PMID- 1383152
TI  - Poly(I.C)-induced interferons enhance susceptibility of SCID mice to systemic
      candidiasis.
AB  - In the absence of any demonstrable T- or B-cell responses, gnotobiotic CB-17 SCID
      (severe combined immunodeficient) mice not only show innate resistance to acute
      systemic (intravenous challenge) candidiasis but also manifest innate resistance
      to systemic candidiasis of endogenous (gastrointestinal tract) origin. Poly(I.
      C), a potent inducer of interferons (IFNs) in vivo, enhanced the susceptibility
      of CB-17 SCID mice to acute systemic candidiasis and to systemic candidiasis of
      endogenous origin, as demonstrated by increased numbers of viable Candida
      albicans in internal organs after poly(I. C) treatment. The poly(I. C)-enhanced
      susceptibility of mice to candidiasis was abrogated by in vivo treatment with
      antibodies to IFN-alpha, -beta, and -gamma. In vivo depletion of natural killer
      cells from SCID mice did not significantly enhance their susceptibility to
      systemic candidiasis or abrogate poly(I. C)-enhanced susceptibility. In vivo and
      in vitro, treatment with poly(I. C) impaired the candidacidal and phagocytic
      activity of thioglycollate-elicited macrophages from SCID mice. Antibody to IFN
      alpha/beta or IFN-beta alone interfered with the ability of poly(I. C) to impair
      the candidacidal activity of macrophages from SCID mice in vitro. These data
      suggest that poly(I. C)-induced interferons can impair the candidacidal activity
      of macrophages in SCID mice and decrease their innate resistance to acute
      systemic candidiasis and to systemic candidiasis of endogenous origin.

PMID- 1383153
TI  - Identification of T- and B-cell epitopes of the S2 and S3 subunits of pertussis
      toxin by use of synthetic peptides.
AB  - To design an optimized synthetic vaccine against whooping cough, we have studied
      the biological and immunological properties of three peptides of the S2 subunit
      and nine overlapping synthetic peptides covering the entire sequence of the S3
      subunit of pertussis toxin (PT). Synthetic peptides corresponding to sequences 18
      to 41, 78 to 108, 134 to 154, and 149 to 176 of S3 were found to be consistently
      capable of stimulating the proliferation of PT-specific T-cell lines primed with
      pertussis toxoid in both BALB/c and A/J strains of mice. All synthetic peptides
      were recognized by rabbit antisera raised against PT or pertussis toxoid. Both S2
      and S3 peptide-keyhole limpet hemocyanin (KLH) conjugates in the presence of
      complete Freund's adjuvant induced peptide-specific antibody responses in
      rabbits, and the antisera raised against S2(1-23), S3(18-41), S3(37-64), and
      S3(149-176) peptide-KLH conjugates cross-reacted with both subunits in the
      immunoblots. All antisera except those against S2(123-154) and S3(103-127)
      reacted with native PT in an enzyme-linked immunosorbent assay (ELISA) with PT
      directly coated onto microtiter wells. In contrast, antisera raised against
      S2(123-154), S3(1-23), S3(18-41), S3(37-64), S3(60-87), and S3(103-127) peptide
      KLH conjugates recognized native PT in a fetuin-PT capture ELISA. S2(78-98), S3(1
      23), and S3(149-176) peptide-KLH conjugates elicited good PT-neutralizing
      antibody responses as judged by the antitoxin CHO cell assay. Identification of
      these B-cell neutralization epitopes and T-cell immunodominant determinants
      represents a first step towards the rational design of a synthetic vaccine
      against whooping cough.

PMID- 1383154
TI  - Protection of mice against Salmonella typhimurium with an O-specific
      polysaccharide-protein conjugate vaccine.
AB  - Serious infections with salmonellae remain a threat in many human populations.
      Despite extensive study of salmonella infections in animals and clinical
      experience with killed cellular vaccines, there are no vaccines against serotypes
      other than Salmonella typhi licensed for human use. Serum antibodies to the O
      specific polysaccharide (O-SP) of salmonellae protect mice against invasive
      infection. In order to render it immunogenic, we have conjugated the O-SP of
      Salmonella typhimurium to carrier proteins by various schemes. O-SP conjugated to
      tetanus toxoid (O-SP-TT) elicited antibodies in outbred mice after three
      subcutaneous injections without adjuvant. The O-SP alone elicited no detectable
      antibody. The antibody response to O-SP-TT was boosted by successive doses and
      consisted of immunoglobulin G (IgG) and IgM. Most mice only produced antibodies
      specific for the abequose (O:4 factor) region of the O-SP. Occasional animals
      also produced antibodies to the core oligosaccharide. Immunized mice were
      protected against intraperitoneal challenge with S. typhimurium, demonstrating a
      160-fold increase in the 50% lethal dose. Passive immunization with conjugate
      induced IgM or IgG also protected against challenge. These results indicate that
      an O-SP-TT conjugate, when given by a route and formulation acceptable for human
      use, protects mice against challenge with S. typhimurium.

PMID- 1383155
TI  - Population transcript accumulation of Pseudomonas aeruginosa exotoxin A and
      elastase in sputa from patients with cystic fibrosis.
AB  - The in vivo regulation of Pseudomonas aeruginosa virulence factors during the
      chronic lung infections associated with cystic fibrosis is poorly understood. We
      have developed an approach for the analysis of transcript accumulation of
      individual virulence factors from the P. aeruginosa populations found in the
      sputa of patients with cystic fibrosis. This method has been named population
      transcript accumulation, since we examine the transcript accumulation patterns in
      RNA extracted from the total bacterial population found in the sputum samples.
      DNA probes specific for P. aeruginosa elastase (lasB) and exotoxin A (toxA) were
      used to examine the population transcript accumulation of 21 sputum samples taken
      from 10 patients. We detected three patterns of population transcript
      accumulation: lasB and toxA, lasB alone, and neither lasB nor toxA. We also
      measured the relative levels of elastase and exotoxin A transcript accumulation
      in 19 of these samples. In the six samples containing both toxA and lasB
      transcripts, we found that the levels of lasB transcripts were consistently
      higher than those of toxA. Differences in the stability of the two mRNA species
      could not completely account for the higher level of lasB population transcript
      accumulation, since we showed that the mRNA half-life of lasB (11 min) was
      similar to that of toxA (10 min). Finally, we showed that elastase transcripts
      could be detected in some samples which contained only mucoid isolates. This
      finding suggests that both mucoid and nonmucoid populations may be transcribing
      lasB in the lungs of patients with cystic fibrosis.

PMID- 1383156
TI  - Isolation and nucleotide sequence of the gene (aniA) encoding the major
      anaerobically induced outer membrane protein of Neisseria gonorrhoeae.
AB  - When grown under anaerobic conditions, Neisseria gonorrhoeae, the etiologic agent
      of the sexually transmitted disease gonorrhea, expresses several novel outer
      membrane proteins. One of these, Pan 1, has an apparent molecular mass of 54 kDa
      in electrophoresis and is recognized by serum samples from patients with
      gonococcal infection. The presence of antibodies to this protein in patient sera
      suggests that Pan 1 is expressed during gonococcal infection and, more
      importantly, that N. gonorrhoeae grows anaerobically in vivo. We have cloned the
      Pan 1 structural gene, aniA, by screening a gonococcal lambda gt11 expression
      library with monospecific, polyclonal anti-Pan 1 antiserum. Three distinct
      immunoreactive recombinants, containing overlapping fragments of DNA, were
      isolated and confirmed to be coding for Pan 1 protein sequences. Northern (RNA
      blot) hybridization of an insert from an aniA recombinant to total gonococcal
      cellular RNA revealed the presence of a 1.5-kb transcript that was specific to
      RNA from anaerobically grown gonococci, indicating that the aniA gene is
      regulated at the transcriptional level and is monocistronic. To characterize the
      aniA gene, we have sequenced the entire 2-kb region spanned by the overlapping
      recombinants. We have also performed primer extension analysis on RNA isolated
      from aerobically and anaerobically grown gonococci in order to define the aniA
      promoter region. Two putative primer extension products specific to organisms
      grown anaerobically were identified by homology to known Escherichia coli
      promoter sequences, suggesting that the regulation of aniA expression involves
      multiple promoter regions.

PMID- 1383157
TI  - Characterization of an amylase-binding component of Streptococcus gordonii G9B.
AB  - The goal of the present study was to begin characterizing the amylase-binding
      component(s) on the surface of Streptococcus gordonii G9B. Alkali extracts but
      not phenol-water extracts of this bacterium inhibited 125I-amylase binding to S.
      gordonii G9B. To identify the bacterial components involved in amylase binding,
      the alkali extract was subjected to affinity chromatography on amylase-Sepharose.
      Immunoblotting with a rabbit antiserum against S. gordonii G9B revealed that a 20
      kDa streptococcal component was eluted from the amylase-Sepharose with 1% sodium
      dodecyl sulfate (SDS), 2 M KSCN, or 0.1 M sodium citrate buffer, pH 4.5.
      Subsequently, the 20-kDa component was prepared from alkali extracts by
      electroelution from preparative SDS electrophoresis or by gel filtration
      chromatography. This component was trypsin sensitive, and an antibody raised
      against it inhibited the binding of 125I-amylase to S. gordonii G9B. Indirect
      immunofluorescence microscopy and immunogold electron microscopy demonstrated
      that both bound amylase and the 20-kDa component were localized to the cell
      division septum on dividing cells or to polar zones on single cells. In addition,
      exponentially growing bacteria bound more 125I-amylase than stationary-phase
      cells did. Collectively, these results suggest that a 20-kDa amylase-binding
      component is present on the surface of the nascent streptococcal cell wall.

PMID- 1383158
TI  - Monoclonal antibodies against the native urease of Helicobacter pylori:
      synergistic inhibition of urease activity by monoclonal antibody combinations.
AB  - Monoclonal antibodies (MAbs) against the native urease of Helicobacter pylori
      NCTC 11637 were found to clearly inhibit the urease activity. Interestingly,
      synergistic inhibition by two MAbs recognizing different subunits was also
      observed. Ten MAbs were produced and classified as two isotypes of the
      immunoglobulin G (IgG) subclass, IgG1, and IgG2a. Western blot (immunoblot)
      analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed
      that five MAbs recognized the large subunit and the other five recognized the
      small subunit of the urease. Among the MAbs, L2 and S2, which recognized the
      large and the small subunits, respectively, were also able to inhibit the urease
      activity of clinical isolates from H. pylori-infected patients. The combination
      of L2 and S2 led to augmented synergistic inhibition. L2, but not S2, could also
      inhibit the urease activity from Helicobacter mustelae; enzyme-linked
      immunosorbent assay and Western blot analysis showed that L2 cross-reacted with
      this urease. These results suggested that the epitope recognized by L2 had a
      structure common to both Helicobacter species and may be involved in the active
      site of the urease. In contrast to the MAbs, a polyclonal antibody in sera from
      mice immunized with H. pylori urease did not have the ability to inhibit H.
      pylori urease activity. However, the polyclonal antibody retained the ability to
      abolish the inhibitory action of these MAbs. Moreover, other MAbs which could not
      inhibit H. pylori urease activity also abolished the inhibitory action.

PMID- 1383159
TI  - Characterization of cell wall proteins from yeast and mycelial cells of Candida
      albicans by labelling with biotin: comparison with other techniques.
AB  - Candida albicans ATCC 26555 blastoconidia and blastoconidia bearing germ tubes
      were metabolically labelled by incubating the cells with 14C-labelled protein
      hydrolysate and were subsequently tagged with biotin. Double-labelled
      (radioactive and biotinylated) cell wall proteins and glycoproteins were
      extracted from intact cells of both growth forms by treatment with 2
      mercaptoethanol (beta ME) and with beta-glucanases (Zymolyase) after treatment
      with beta ME. The beta ME- and Zymolyase-extracts were separated by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and western blotted
      (immunoblotted) to nitrocellulose paper. Polyacrylamide gels were stained with
      Coomassie blue and processed for fluorography. Western blot analysis was
      performed either with peroxidase conjugated-concanavalin A (ConA) or Extravidin.
      Blotted proteins were also reacted with polyclonal antibodies and monoclonal
      antibodies against mannoprotein components from mycelial cell walls of the ATCC
      26555 strain. Labelling with biotin allowed identification of a complex array of
      cell wall protein and glycoprotein components within a very wide molecular mass
      range (from 650 to 13 kDa). These appeared to be genuine cell wall components.
      Biotinylated high-molecular-mass glycoproteins that were not stained with
      Coomassie blue or that appeared as poorly resolved polydisperse bands by indirect
      ConA-peroxidase staining of Western blots were detected as sharply defined bands
      following reaction with the Extravidin-peroxidase conjugate. Biotinylated
      molecules retained unaltered reactivities against ConA, polyclonal antibodies,
      and monoclonal antibodies.

PMID- 1383160
TI  - Novel adjuvant action of lipopolysaccharides that possess mannose
      homopolysaccharides as O-specific polysaccharides on immune responses to
      nonimmunogenic autoantigens in mice.
AB  - The adjuvant action of various lipopolysaccharides on immune responses to
      syngeneic tissue extract in mice was examined. Only lipopolysaccharides
      possessing the linear mannose homopolysaccharides as O-specific polysaccharides
      exhibited definite adjuvant action on immune responses to the autoantigens. The
      intensity of this adjuvant activity of lipopolysaccharide from Klebsiella O3
      seemed to be the strongest.

PMID- 1383161
TI  - Characterization of a Borrelia burgdorferi dnaJ homolog.
AB  - The gene encoding a Borrelia burgdorferi DnaJ homolog, located immediately 3' of
      the hsp70 gene, was characterized. Although there is a single copy of the dnaJ
      gene on the spirochetal chromosome, two distinct dnaJ transcripts are detected in
      B. burgdorferi RNA. RNA blot analysis indicates that the dnaJ gene can be
      transcribed alone or as part of a larger transcript containing the hsp70 homolog.

PMID- 1383164
TI  - Isolation of exfoliated colonic epithelial cells, a novel, non-invasive approach
      to the study of cellular markers.
AB  - Human stool is a heterogeneous mixture of non-digestible food residues, bacteria,
      cells exfoliated from the gastrointestinal mucosa and other secretory products.
      We have demonstrated that fresh human stools dispersed in a buffered saline
      solution can be fractionated over Percoll/BSA gradients to yield 9 discrete bands
      of cells in the density range of rho 1.033 to 1.139 and which could be further
      purified over Histopaque 1077. Enzyme-linked immunoassays (ELISA) for colon
      specific antigen (CSA) and cytokeratins (CK) were positive. Western blot analysis
      showed the presence of 3 cytokeratin bands in the 40-kDa to 60-kDa range
      suggestive of cytokeratins 8, 18, and 19. Fluorescence flow-cytometric analysis
      of these cells using antibodies against CSA, CK, the blood-group antigens,
      carcinoembryonic antigen (CEA), non-mucus-secreting columnar-epithelium-specific
      MAb PR1A3, and to mucus-secreting colonic-epithelium-specific MAb PR5D5 showed
      varying degrees of reactivity. Expression of the blood-group phenotype suggests
      that cells from the proximal half of the colon had survived the transit, since in
      the adult expression of this marker is limited to cells from the proximal region
      of the colon. In this report we demonstrate the feasibility of studying, non
      invasively, cell-specific markers on exfoliated cells isolated from stools. The
      evidence strongly suggests that almost all the cells are of colonic origin.

PMID- 1383162
TI  - Combustion of diesel fuel from a toxicological perspective. I. Origin of
      incomplete combustion products.
AB  - Since the use of diesel engines is still increasing, the contribution of their
      incomplete combustion products to air pollution is becoming ever more important.
      The presence of irritating and genotoxic substances in both the gas phase and the
      particulate phase constituents is considered to have significant health
      implications. The quantity of soot particles and the particle-associated organics
      emitted from the tail pipe of a diesel-powered vehicle depend primarily on the
      engine type and combustion conditions but also on fuel properties. The quantity
      of soot particles in the emissions is determined by the balance between the rate
      of formation and subsequent oxidation. Organics are absorbed onto carbon cores in
      the cylinder, in the exhaust system, in the atmosphere and even on the filter
      during sample collection. Diesel fuel contains polycyclic aromatic hydrocarbons
      (PAHs) and some alkyl derivatives. Both groups of compounds may survive the
      combustion process. PAHs are formed by the combustion of crankcase oil or may be
      resuspended from engine and/or exhaust deposits. The conversion of parent PAHs to
      oxygenated and nitrated PAHs in the combustion chamber or in the exhaust system
      is related to the vast amount of excess combustion air that is supplied to the
      engine and the high combustion temperature. Whether the occurrence of these
      derivatives is characteristic for the composition of diesel engine exhaust
      remains to be ascertained. After the emission of the particles, their properties
      may change because of atmospheric processes such as aging and resuspension. The
      particle-associated organics may also be subject to (photo)chemical conversions
      or the components may change during sampling and analysis. Measurement of
      emissions of incomplete combustion products as determined on a chassis
      dynamometer provides knowledge of the chemical composition of the particle
      associated organics. This knowledge is useful as a basis for a toxicological
      evaluation of the health hazards of diesel engine emissions.

PMID- 1383165
TI  - Serological and immunological studies with a hexane extract of Babesia bovis
      infected erythrocytes.
AB  - Antigenic and immunogenic activities of a hexane extract from Babesia bovis
      infected erythrocytes were investigated. Positive ELISA and IFAT reactions were
      obtained with bovine antisera to B. bovis and B. bigemina produced by natural
      infection and rabbit antisera to the hexane extract, respectively. In contrast,
      negative ELISA reactions were obtained with Anaplasma marginale antisera
      indicating that the antigen(s) is specific for the genus Babesia. The IFAT
      clearly demonstrated that the antigen was associated with the parasite and the
      infected erythrocyte and not present in uninfected erythrocytes. Furthermore,
      cross-reactions with Babesia bigemina antisera suggested that serological cross
      reactivity in bovine Babesia species is at least due in part to lipid or lipid
      associated antigens.

PMID- 1383163
TI  - Combustion of diesel fuel from a toxicological perspective. II. Toxicity.
AB  - Epidemiological data and results of toxicity studies in experimental animals
      indicate the possible health risk of diesel exhaust exposure. Acute effects of
      this exposure include odor, eye irritations, lung function decrements,
      cardiovascular symptoms, and some non-specific effects. Most of these effects are
      reported among persons highly exposed to diesel exhaust. Lung function decrements
      are reported as chronic effects. Another chronic effect that has been studied
      extensively among occupationally exposed persons in lung cancer. In addition to
      lung cancer, but at a less frequent rate, an enhanced incidence of bladder cancer
      is reported. The carcinogenic action of diesel exhaust exposure is ascribed to
      effects of the soot particles, particle-associated organics, and/or gas phase
      compounds. Direct effects of the particle load may include retardation of lung
      clearance, inflammation, and increased cell proliferation. These effects were all
      demonstrated in rodents. The particles may also prolong the residence time of
      particulate organics or induce the generation of reactive oxygen species. These
      compounds are known to react with macromolecules, causing lipid peroxidation, DNA
      damage, and/or activation of other genotoxic substances such as polycyclic
      aromatic hydrocarbons (PAHs). However, these results have not yet been confirmed
      in mammals in vivo. A direct interaction of particles with lung tissue is also
      suggested as a cause of cancer but a mechanism for this interaction has not yet
      been proposed. Organics associated with the particles are known to contain
      genotoxic properties attributable to PAHs and their derivatives. A number of
      these compounds are also identified as carcinogens in animal studies. However, it
      is not clear whether parent PAHs, their nitro-, oxy-, alkylated, or heterocyclic
      derivatives, or possibly other compounds are principally responsible for inducing
      tumors in the lungs of animals after diesel exhaust exposure. Furthermore, the
      mechanism of the bioavailability of these organics is not completely understood.
      The effects of gas phase constituents on the carcinogenic properties of the
      particles and/or particle-associated organics either have not been investigated
      or the findings have been inconclusive.

PMID- 1383166
TI  - Solid phase synthesis of peptides containing the non-hydrolysable analog of
      (O)phosphotyrosine, p(CH2PO3H2)Phe. Application to the synthesis of 344-357
      sequences of the beta 2 adrenergic receptor.
AB  - Studies about phosphorylation-dephosphorylation mechanisms require the
      development of probes capable of being used in in vitro and in vivo conditions.
      We show in this work that the chemically and enzymatically stable p(CH2PO3H2)Phe
      analog of (O)phosphotyrosine can be easily introduced in peptides by the solid
      phase method. It has been incorporated in the 344-357 sequence of the beta 2
      adrenergic receptor in place of the Tyr residue in position 350 and/or 354 in
      order to investigate the role of tyrosine phosphorylation in the receptor agonist
      induced down-regulation. Since p(CH2PO3H2)Phe is an ionized hydrophilic residue,
      peptides containing this amino acid do not easily permeate the cellular
      membranes. Therefore the modified amino acid was introduced in the synthetic
      pathway in its N-Boc-p(CH2PO3Et2)Phe form, which could be partially or completely
      deprotected. Coupling steps, including that of the new amino acid, were performed
      with good yields (approximately 60% total yield) and further deprotections
      provided both the p(CH2PO3H2)Phe and p(CH2PO3HEt)Phe containing peptides with
      yields of around 20% each. The structure of the peptides was assessed by NMR,
      mass spectroscopy and amino acid analysis and the new amino acid was
      characterized under its phenylthiocarbamyl form (PTC).

PMID- 1383167
TI  - Distribution of nerve endings and sensory neuropeptides in rat synovium, meniscus
      and bone.
AB  - The nervous system collects information from the outer world by specific senses
      and from the interior milieu by somatic senses. This information is processed and
      stored in memory and affects various bodily functions through the efferent arm of
      the nervous system. The efferent chemical neuropeptide message is transported
      intra-axonally to the site of action, which imparts site-specificity to the
      peripheral, paracrine neuropeptide effects. In the present study,
      immunohistochemistry using the immunoperoxidase method with nickel amplification
      was applied to visualize the topographical distribution of articular nerve fibres
      and nerve endings using the markers PGP 9.5 and synaptophysin, respectively.
      Furthermore, to get a comprehensive idea of the sensory innervation of the
      articular and para-articular tissue, antisera to calcitonin gene-related peptide
      (CGRP) and substance P were employed. Samples were collected after fixation by
      perfusion followed by immersion in fixative and decalcification by a special
      method, which also allows studies of the bone innervation. PGP 9.5- and
      synaptophysin-immunoreactive type IVa and IVb nerve fibres and endings were found
      in the synovial lining and sublining tissue and in the vascularized peripheral
      parts of the menisci. Furthermore, periosteum, bone marrow and the epiphyseal
      growth plates were also innervated, whereas innervation of the diaphyseal and
      metaphyseal bone was more sparse. PGP 9.5- and synaptophysin-immunoreactive
      nerves were also characterized by their CRGP, and to some extent, substance P
      content. Because of their distribution, the peripheral peptide-containing type
      IVa and IVb nerve fibres and nerve endings are in a position to participate in
      the pathogenesis of arthritis, including aspects of nociception, tissue
      remodelling and neurogenic inflammation.

PMID- 1383168
TI  - Are we seeking the correct targets for therapeutic intervention?
AB  - In this plenary symposium paper, the authors review the physiological development
      of rheumatoid arthritis, the rationale for the manipulation of the eicosanoid
      pathway, the inhibition of tissue destruction, and angiogenesis. They proceed to
      discuss immunotherapy under the headings of intercellular adhesion, the induction
      of tolerance, and novel immunomodulatory agents. They conclude that the
      palliative treatment of the acute aspect of inflammation will continue by
      necessity into the foreseeable future. Whilst the selectivity and tolerability of
      existing and novel modulators of the acute inflammatory response are being
      improved, the alleviation of joint destruction in the long-term rheumatoid
      patient will depend on the manipulation of those mechanisms involved in the
      maintenance of the chronic inflammatory process. The ultimate goal for the
      therapy of the future, namely remission, can now be pursued with good reason for
      success, with the application of modern molecular biological techniques which
      will increase not only our understanding of autoimmunity, but also our ability to
      manipulate the immune system with profound selectivity. Central to the
      realization of these goals are the long-term chronic models of inflammatory joint
      disease, such as granuloma-cartilage implants and polyarticular and monoarticular
      arthritides, which will be essential for the assessment of the therapeutic
      promise of these exciting new developments.

PMID- 1383169
TI  - Complications of vitrectomy.

PMID- 1383171
TI  - [Is hemodilution with HAES a reliable therapeutic procedure in cerebral
      infarct?].

PMID- 1383170
TI  - Modified method of radical retropubic prostatectomy for localized prostatic
      cancer.
AB  - A modified method of retropubic radical prostatectomy was devised. The root of
      the penis was compressed and the bilateral internal iliac arteries were clamped
      before the dissection of the prostate. The urethra was divided at the junction of
      the prostate and bladder so that the bladder stump thus created has the size of
      the tip of the middle finger. Vesicourethral anastomosis was done by Vest
      procedure. By this method 24 patients were operated. All patients except one were
      alive without recurrence after the mean follow-up of 32 months. This method seems
      to be good enough to recommend.

PMID- 1383172
TI  - In vitro models of lymphocyte transendothelial migration.
AB  - The processes of lymphocyte-endothelial cell interaction and the in vitro assays
      employed in their study are the subjects of this review. In motility assays in
      porous filters and gel matrices, it has been shown that lymphocyte migration can
      be modulated by interleukin-2 (IL-2), IL-3, IL-4, IL-6, and IL-8. Cytokines can
      also modulate lymphocyte-endothelial adhesion. Endothelial intercellular adhesion
      molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are induced or
      upregulated by IL-1 or tumor necrosis factor. In addition, interferon-gamma
      upregulates ICAM-1, and IL-4 can induce VCAM-1. The roles of these cytokines and
      adhesion molecules in transendothelial migration may be studied in assays in
      which lymphocytes penetrate layers of cultured endothelial cells. These models
      can distinguish lymphocyte adhesion from subsequent migration. Using such models,
      we and others have obtained evidence that both lymphocyte function-associated
      antigen-1 (LFA-1)/ICAM-1 and very late activation antigen 4 (VLA-4)/VCAM-1
      interactions mediate lymphocyte adhesion to endothelial cells, but that LFA
      1/ICAM-1 interactions play a greater role in transendothelial migration.

PMID- 1383173
TI  - Cardiac anatomy instruction by ultrafast computed tomography versus cadaver
      dissection.
AB  - RATIONALE AND OBJECTIVES: This prospective study was designed to determine to
      what extent an ultrafast computed tomography (UFCT) videotape of the heart could
      enhance or substitute for cadaver dissection in teaching anatomy to first-year
      medical students. METHODS: A student population (n = 180) was randomized into
      four groups. Group 1 (control) received no instruction, group 2 viewed the
      videotape, group 3 participated in cardiac dissection, and group 4 performed
      cardiac dissection and viewed the videotape. After randomized instruction, each
      group was tested with 10 UFCT static cardiac images and 8 cardiac cadaver
      specimens. A different population consisting of nonrandomized fourth-year medical
      students also was tested. RESULTS: The results point to an interaction between
      instruction and the manner in which it was assessed. There was more carryover
      from the videotape-acquired knowledge to specimens than from dissection-acquired
      knowledge to UFCT images. CONCLUSIONS: Cardiac UFCT instruction resulted in
      dramatically improved image testing performance. This image-acquired knowledge
      was not sufficiently transferred to cardiac specimen identification; thus,
      videotape instruction should not replace dissection for teaching cardiac anatomy.
      Video provided instruction benefits beyond that gained through general clinical
      experience.

PMID- 1383174
TI  - Determination of prostate volume with transrectal ultrasound for cancer
      screening. Part I. Comparison with prostate specific antigen assays.

PMID- 1383175
TI  - Management of the final 24 hours.
AB  - The management of the final 24 hours of life of 100 patients, dying in Our Lady's
      Hospice is reviewed. This review suggests that management might be improved by
      better contact between general hospitals and hospice/home care teams concerning
      the timing of patient transfer. The frequency of symptoms in the dying patient,
      even where many are semi-comatose, is highlighted. The main distressing symptoms
      are pain, excessive respiratory secretions and agitation. Our review confirms
      reliance on standard palliative medications such as morphine, however identifies
      the benefit of such newer preparations as hydromorphone and midazolam. Management
      might be improved by the earlier usage of hyoscine subcutaneously and stopping
      the use of intramuscular diazepam. Attention to potential hyoscine toxicity and
      untreated pyrexia may ease pre-terminal agitation. The dying patient's family
      also needs attention to complete the optimal management of the final 24 hours.

PMID- 1383177
TI  - Similarity of copper and technetium binding sites in human IgG.
AB  - Kits for direct labeling of IgG with 99mTc were used without modification for the
      preparation of [67Cu]IgG. The IgG was pre-treated to generate thiolate groups
      which would bind 67Cu. The direct labeling of reduced IgG with 67Cu was highly
      efficient, resulting in approx. 95% 67Cu binding. Non-reduced IgG (negative
      control) had labeling efficiencies of less than 10%. IgG pre-exposed to Cu(II)
      had reduced amounts of 99mTc bound to it. The results demonstrate a direct
      relationship between copper- and 99mTc-binding sites in IgG.

PMID- 1383176
TI  - Current strategies in the nursing care of infants with hypoplastic left-heart
      syndrome undergoing first-stage palliation with the Norwood operation.
AB  - Hypoplastic left-heart syndrome is a common congenital heart defect that carries
      a mortality rate of 95% in the first month of life if left untreated. In the
      past, surgical options were not accepted. However, recent success with the
      Norwood operation as part of a staged reconstructive approach has renewed
      interest in operative intervention for these critically ill neonates. Assessment
      of the balance between systemic and pulmonary blood flow is critical to maintain
      cardiac output and systemic saturation.

PMID- 1383178
TI  - High dose rate brachytherapy in patients with local recurrences after
      radiotherapy of non-small cell lung cancer.
AB  - Thirty-one patients with recurrences of locally advanced Stage III lung cancer
      were treated with high dose rate brachytherapy. All patients had previously
      received a full course external beam irradiation. All treatments were performed
      under topical anaesthesia and took 6-14 min depending on the strength of the
      Iridium-192 source. The high dose rate brachytherapy was calculated as 10 Gy at
      one cm from the source axis for each session and this was repeated every 2 weeks
      to a maximum of three sessions. All treatments were well tolerated and no
      immediate treatment related complications were observed. Response evaluation 6
      weeks after high dose rate brachytherapy showed that there was a partial response
      in 22 patients and nine patients were non-responders. Median survival was 7 and 3
      months, respectively. All non-responders had initially presented with a T4N3
      tumor. Ten patients died because of fatal pulmonary hemorrhages 2-24 weeks after
      brachytherapy and three others died because of a bronchial fistula. Endobronchial
      brachytherapy appears to be a valuable treatment alternative for local
      palliation. However, the relatively high number of complications at follow-up
      warrants further investigation to establish the optimal benefit to be derived
      from high dose rate brachytherapy treatment of locally advanced Stage III tumors.

PMID- 1383179
TI  - Identification of surgical biopsy borders by use of india ink.
AB  - Separation of surgical biopsy borders from artifactual borders created during
      trimming of biopsy specimens is necessary to avoid misinterpretation of
      histologic borders. Misinterpretation of a contaminated trimming border as a
      surgical border may lead to additional surgery and excessive removal of normal
      tissue. Likewise, a neoplasm may regrow locally or metastasize if a surgical
      border infiltrated with neoplastic cells is falsely assumed to be an artifactual
      trimming border. The use of India ink for distinguishing between surgical biopsy
      borders and artifactual borders was evaluated. Ten normal tissue specimens from 8
      types of tissue (skin, small intestine, urinary bladder, bone, muscle, lung,
      large intestine, and uterus) were obtained from freshly euthanatized dogs. The
      specimens were painted with India ink and examined for adherence of the ink to
      the cut surface of the specimen. Adherence of the ink was observed in all
      specimens with the exception of the cut surface of the lung. Twenty-five biopsy
      specimens from dogs with clinical cases of disease were similarly painted with
      India ink and evaluated. Twenty-two were identified as neoplastic and 3 as
      inflammatory lesions. Wedges of tissue were obtained from the center of the
      biopsy specimens to purposely create borders that contained neoplastic tissue.
      These positive controls were painted with India ink to evaluate the effect of the
      ink on the histologic appearance of the neoplastic cells. Distortion or
      alteration of the cellular architecture was not observed in any of the normal
      specimens, specimens from dogs with clinical cases, or positive controls. The use
      of India ink for delineation of biopsy borders is a simple technique that
      presents few technical difficulties.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383180
TI  - Non-transformed, but not ras/myc-transformed, serum-free mouse embryo cells
      recover from growth suppression by azatyrosine.
AB  - The anti-proliferative effect of azatyrosine, a newly discovered antibiotic from
      Streptomyces, was examined in Balb/c-originated serum-free mouse embryo (SFME)
      cells and transformed ras/myc SFME cells which have activated human c-Ha-ras
      genes. Azatyrosine suppressed their growth in a concentration-dependent manner.
      Growth suppression in both cells was detectable within 2 days after culture with
      250 micrograms/ml azatyrosine. Non-transformed SFME cells, however, regained
      rapid growth after 6 days even in the presence of azatyrosine, whereas ras/myc
      SFME cells did not recover from the suppression. Despite the growth inhibition of
      ras/myc SFME cells, expression of human ras in the cells was not inhibited by
      azatyrosine. Meanwhile, SFME cells have the ability to express glial fibrillary
      acidic protein (GFAP). This expression is induced by serum-supplemented medium,
      though the serum inhibits the growth of SFME cells. Azatyrosine did not induce
      GFAP in ras/myc SFME cells, but inhibited growth. Furthermore, azatyrosine did
      not induce GFAP in SFME cells, and had no effect upon the expression of GFAP
      induced by serum in these cells. These results suggest that azatyrosine inhibited
      the growth of ras/myc SFME cells through a mechanism independent of those
      involved in growth inhibition and induction of GFAP expression by serum in SFME
      cells.

PMID- 1383181
TI  - Insulin-like growth factors and binding proteins in ruminants and their
      nutritional regulation.
AB  - Insulin-like growth factors (IGF) are important mediators of growth, lactation,
      reproduction, and health. Considerable information on their role in ruminant
      animals has been learned in the past several years, but the precise mechanisms of
      their action are not known. The exact biological response of target cells is
      undoubtedly determined by the developmental state of the cell and synergism with
      other growth factors. Overall, somatomedins and their binding proteins seem to be
      major links between cellular developmental processes and nutrient supply. The
      mechanism by which nutrients control biological actions of somatomedins is not
      known but clearly involves the synthesis of IGF, as well as their binding
      proteins and receptors. In ruminants, severe feed restriction decreases
      circulating concentrations of IGF-I, whereas subtle alterations typical of those
      that occur in production systems have minimal effect. However, the responses of
      IGF to somatotropin are affected by modest alterations in nutritional status,
      including differences in nutritional status that are typically encountered in
      animal production systems.

PMID- 1383182
TI  - Haemagglutinins and fimbriae of soft rot Erwinias.
AB  - Strains of phytopathogenic soft rot Erwinia spp. were examined for haemagglutinin
      (HA) production. Mannose-sensitive HA was found only in five of 15 strains of E.
      carotovora subsp. carotovora. Mannose-resistant HA (MRHA) was found in 12 of 15
      strains of E.c. carotovora, ten of 13 strains of E.c. subsp. atroseptica and the
      single strain of E.c. subsp. betavasculorum, as well as all seven strains of E.
      chrysanthemi. MRHA, detectable only in a microtitre tray HA assay was of either
      broad- or narrow-spectrum activity when examined against blood of seven different
      animal species and could be inhibited by the beta-galactoside asialofetuin.
      Fimbriae of ca 10 nm diameter were found on MRHA(+) bacteria E.c. carotovora and
      E.c. atroseptica.

PMID- 1383183
TI  - Differential uptake of endothelin-1 by the coronary and pulmonary circulations.
AB  - Substantial removal of the vasoconstrictor peptide endothelin-1 (ET-1) by the
      pulmonary circulation has been reported to occur in perfused guinea pig and rat
      lungs. We examined the uptake of ET-1 by coronary and pulmonary circulations of
      the rabbit by measuring single-pass extraction of ET-1 in the isolated heart and
      lung. In separate experiments, each organ was perfused at 30 ml/min with Krebs
      albumin (3%) solution. A bolus of 125I-ET-1 and [14C]dextran in 0.3 ml Krebs
      albumin solution was injected, and extraction of endothelin (EET), relative to
      that of an intravascular reference indicator, [14C]dextran, was determined by
      multiple indicator-dilution technique. EET was 5 +/- 2% (SE) in the heart and 49
      +/- 4% in the lung. Increasing flow rate in the lung preparation to approximate
      the mean transit time in the heart preparation did not significantly alter EET.
      Despite insignificant uptake of ET-1, the coronary circulation extracted an
      angiotensin-converting enzyme inhibitor (351A) and metabolized a synthetic
      angiotensin-converting enzyme substrate (benzoyl-phenyl-alanyl-proline), both
      properties of the normal pulmonary circulation. We therefore conclude that there
      is no significant ET-1 uptake in the coronary vascular bed.

PMID- 1383184
TI  - Segmental vascular responses to voltage-gated calcium channel potentiation in rat
      lung.
AB  - We determined lung vascular responses to voltage-gated Ca2+ channel potentiation
      with BAY K 8644 (BAY). We anesthetized 46 rats (Sprague-Dawley; halothane and
      pentobarbital) and then excised and perfused their lungs at constant blood flow
      of 25 +/- 2 (SE) ml.kg-1.min-1 at constant airway and left atrial pressures of 5
      and 6 cmH2O, respectively. Pulmonary arterial pressure (Ppa) increased from 13.3
      +/- 0.3 cmH2O at baseline to 17.3 +/- 1.3 cmH2O after BAY (2.8 x 10(-6) M; n = 5;
      P less than 0.01). As determined by micropuncture, arteriolar and venular (Pven)
      pressures did not change. Increase of perfusate Ca2+ (16 x 10(-3) M; n = 8)
      similarly increased Ppa. NG-mono-methyl-L-arginine (2 x 10(-4) M), an inhibitor
      of endothelium-derived relaxing factor, augmented the pressor effect of BAY when
      given after (n = 4) but not before (n = 4) BAY (P less than 0.01). Prior
      cyclooxygenase blockade with indomethacin (5 mg/kg; n = 5) attenuated the Ppa
      response to BAY (P less than 0.01). None of these agents changed Pven. To confirm
      vasoactivity in veins, we induced smooth muscle depolarization with KCl (20 x 10(
      3) M; n = 6) and receptor-mediated responses with histamine (3 x 10(-4) M; n =
      7). Both of these agents increased Pven markedly (P less than 0.01). We interpret
      that, in rat lung, BAY causes arterial but not venous constriction, because the
      venous segment differs from the arterial with regard to Ca2+ channel
      potentiation.

PMID- 1383185
TI  - Immunologic mast cell-mediated responses and histamine release are attenuated by
      heparin.
AB  - Heparin has been shown to act as a competitive inhibitor of inositol 1,4,5
      triphosphate (InsP3) receptors in various cell types. Because InsP3 is one of the
      second messengers involved in stimulus-secretion coupling in mast cells, it is
      possible that heparin may inhibit mast cell-mediated reactions. Therefore, in
      allergic sheep, we tested this hypothesis in two mast cell-mediated reactions
      induced by immunologic and nonimmunologic stimuli: immediate cutaneous reaction
      (ICR) and acute bronchoconstrictor response (ABR). In 12 sheep allergic to
      Ascaris suum antigen, the surface area of the skin wheal was determined 20 min
      after intradermal injection (0.05 ml) of increasing concentrations of specific
      antigen, compound 48/80, and histamine, without and after pretreatment with
      heparin (100, 300, or 1,000 U/kg i.v.). Antigen, compound 48/80, and histamine
      produced concentration-dependent increases in ICR. Heparin "partially" inhibited
      the ICR to antigen and compound 48/80 in a dose-dependent manner without
      modifying the ICR to histamine. The heparin preservative benzyl alcohol was
      ineffective. In 11 additional sheep, specific lung resistance was measured before
      and after inhalation challenges with antigen, compound 48/80, and histamine
      without and with aerosol heparin pretreatment (1,000 U/kg). Heparin blocked the
      antigen- and compound 48/80-induced bronchoconstriction without modifying the
      airway effects of histamine. In isolated human uterine mast cells, heparin
      inhibited the anti-immunoglobulin E- but not the calcium ionophore- (A23187)
      induced histamine release. These data suggest that heparin inhibits the ICR and
      ABR induced by stimuli that produce immunologic and nonimmunologic mast cell
      degranulation without attenuating the effects of histamine.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1383186
TI  - Radiological case of the month. Pancreatic head carcinoma.

PMID- 1383187
TI  - Factor validity and norms for the aberrant behavior checklist in a community
      sample of children with mental retardation.
AB  - The Aberrant Behavior Checklist (ABC) is a 58-item rating scale that was
      developed primarily to measure the effects of pharmacological intervention in
      individuals living in residential facilities. This study investigated the use of
      the ABC in a sample of community children with mental retardation. Teacher
      ratings on the ABC were collected on 666 students attending special classes. The
      data were factor analyzed and compared with other studies using the ABC. In
      addition, subscales were analyzed as a function of age, sex, and classroom
      placement, and preliminary norms were derived. A four-factor solution of the ABC
      was obtained. Congruence between the four derived factors and corresponding
      factors from the original ABC was high (congruence coefficients ranged between
      .87 and .96). Classroom placement and age had significant effects on subscale
      scores, whereas sex failed to affect ratings. The current results are
      sufficiently close to the original factor solution that the original scoring
      method can be used with community samples, although further studies are needed to
      look at this in more detail.

PMID- 1383188
TI  - Validity and reliability of the infant behavioral summarized evaluation (IBSE): a
      rating scale for the assessment of young children with autism and developmental
      disorders.
AB  - The Infant Behavioral Summarized Evaluation (IBSE) is a rating scale adapted from
      the Behavioral Summarized Evaluation (BSE) and specifically related to the
      assessment of behaviors of young children having autistic disorders. Content
      validity and reliability studies described in the paper were made from behavior
      ratings of videotapes for 89 children aged from 6 to 48 months. Results show a
      significant group of 19 items including some characteristic early autistic
      behaviors (communicative and social abnormalities) and some that are less
      commonly described in the syndrome (attentional, perceptive, and adaptive
      disorders). The value of the use of this scale for clinicians and professionals
      involved in behavioral evaluations and treatment of young children with
      developmental disorders and the necessity for further psychometric investigations
      are discussed.

PMID- 1383189
TI  - A follow-up study of 201 children with autism in Kyushu and Yamaguchi areas,
      Japan.
AB  - A follow-up survey was conducted on 201 young adults with autism who were 18 or
      older (mean age, 21.5). All had participated previously in intensive therapeutic
      camping or had therapeutic involvement at medical consultation agencies to
      evaluate their outcome. Their social outcome was better than that previously
      reported in Japan. Although 31.5% had shown marked deterioration during
      adolescence, 43.2% had shown marked improvement during that period. Possible
      factors contributing to these results are discussed.

PMID- 1383190
TI  - Postural control in children with autism.
AB  - Postural control was evaluated in samples of autistic, normal, and mentally
      retarded children in this pilot study using a recently developed, computerized
      posturographic procedure. A battery of postural positions was administered
      including postures involving some degree of "stress" (e.g., occluded vision or
      standing on pads). The postural patterns of children with autism differed from
      those observed in normal children, in mentally retarded children, and in adults
      with vestibular disorders. In comparison to normal children the autistic subjects
      were less likely to exhibit age-related changes in postural performance and
      postures were more variable and less stable with more lateral sway. Autistic
      subjects also exhibited a "paradoxical" response of greater stability with more
      "stressful" postures, putting excessive weight on one foot, one toe, or one heel.
      The implications for neuroanatomical models of autism are discussed.

PMID- 1383191
TI  - New structural features of the antigenic extracellular polysaccharides of
      Penicillium and Aspergillus species revealed with exo-beta-D-galactofuranosidase.
AB  - To study the structures of the epitopes of the extracellular polysaccharides from
      Penicillium and Aspergillus species, an exo-beta-D-galactofuranosidase was
      purified from a commercial crude enzyme preparation from Trichoderma harzianum.
      Analysis of ring size and linkage position of the galactose residues of the
      extracellular polysaccharide of Penicillium digitatum, before and after enzymatic
      treatment, was determined by the reductive-cleavage technique. In addition to
      terminal and beta (1-5)-linked galactofuranosides, beta (1-6)-linked and beta
      (1,5,6)-linked branched galactofuranose residues could be identified. After
      degradation with the purified exo-beta-D-galactofuranosidase, all initial
      linkages of the galactofuranose residues were still present, but the amount of
      beta (1-5)-linked galactofuranose residues had decreased considerably. Treatment
      of the extracellular polysaccharides of Penicillium and Aspergillus species with
      the purified exo-beta-D-galactofuranosidase resulted in complete disappearance of
      the enzyme-linked immunosorbent assay reactivity of these polysaccharides, using
      immunoglobulin G antibodies raised against P. digitatum. Therefore, with the use
      of this enzyme, it was proved that the beta (1-5)-linked galactofuranosyl
      residues only are responsible for the antigenicity of the extracellular
      polysaccharides of Penicillium and Aspergillus molds. A new structural model for
      the antigenic galactofuranose side chains of the galactomannan from P. digitatum
      is proposed.

PMID- 1383192
TI  - A gene complex coding for the membrane-bound hydrogenase of Alcaligenes eutrophus
      H16.
AB  - One of the key enzymes in the chemolithoautotrophic metabolism of Alcaligenes
      eutrophus H16 is a dimeric, membrane-associated hydrogenase. The genetic
      determinants of this enzyme are located on the endogenous megaplasmid pHG1 (G.
      Eberz, C. Hogrefe, C. Kortluke, A. Kamienski, and B. Friedrich, J. Bacteriol.
      168:636-641, 1986). Complementation studies showed that the information required
      for the formation of active membrane-bound hydrogenase occupies more than 7.5 kb
      of megaplasmid DNA. We cloned and sequenced this region and identified the genes
      encoding the two hydrogenase subunits (hoxK and hoxG). The nucleotide sequence
      contains nine additional closely spaced open reading frames. Immunoelectron
      microscopy showed that the gene product of one of these open reading frames
      (hoxM) is involved in the process leading to the attachment of hydrogenase to the
      membrane. Other open reading frames may encode additional processing functions
      and components of a hydrogenase-linked electron transport chain. Analysis of Tn5
      B21-mediated transcriptional fusions provided evidence that the structural genes
      and accessory functions belong to at least three coordinately regulated
      transcriptional units.

PMID- 1383193
TI  - Spiroplasma citri UGG and UGA tryptophan codons: sequence of the two tryptophanyl
      tRNAs and organization of the corresponding genes.
AB  - From the total tRNAs of Spiroplasma citri, we isolated and purified two tRNA(Trp)
      species by using chromatography on an RPC-5 column followed by denaturing
      polyacrylamide gel electrophoresis. The sequence of the two tRNAs, as well as the
      sequences of the corresponding genes, were determined. One of the two tRNA(Trp)
      species has a CCA anticodon and is able to pair with the universal UGG tryptophan
      codon, while the second has a U*CA (U* is a modified uridine) anticodon and is
      able to pair with UGA but also with UGG in accordance with the "U:N wobble" rule.
      Thus, in S. citri, UGA is not a stop codon but codes for tryptophan. The two
      tRNA(Trp) genes, together with a third tRNA gene, tRNA(Ser) (CGA), belong to a
      single transcription unit. The nucleotide sequences of the two tRNA(Trp) species
      show 82.9% similarity. The two spiroplasmal tRNA(Trp) species can be
      aminoacylated by using an aminoacyl-tRNA synthetase fraction from S. citri. In
      contrast, the enzyme fraction from Escherichia coli aminoacylates tRNA(Trp) (CCA)
      but not tRNA(Trp) (U*CA).

PMID- 1383194
TI  - Site-specific integration of the Haemophilus influenzae bacteriophage HP1:
      location of the boundaries of the phage attachment site.
AB  - Plasmids containing DNA segments from the attachment region of phage HP1 were
      constructed and tested for the ability to replace the phage attachment site
      substrate in site-specific recombination reactions. The distance separating the
      boundaries of the functional site was 418 bp. Replacements within the 11-residue
      segment 5'-GGCGGTTATCG at the left boundary or within the 12-residue segment 5'
      GGATTTTTTGAA at the right boundary abolished substrate activity. A segment of the
      418-residue sequence preserves the integrity of an operon of three Haemophilus
      influenzae tRNA genes after HP1 insertion within the coding sequence.

PMID- 1383195
TI  - Ribosomes exist in large excess over the apparent demand for protein synthesis
      during carbon starvation in marine Vibrio sp. strain CCUG 15956.
AB  - Carbon starvation induces the development of a starvation- and stress-resistant
      cell state in marine Vibrio sp. strain S14 (CCUG 15956). The starved cells remain
      highly responsive to nutrients during prolonged starvation and exhibit
      instantaneous severalfold increases in the rates of protein synthesis and RNA
      synthesis when substrate is added. In order to elucidate the physiological basis
      for the survival of cells that are starved for a long time, as well as the
      capacity of these cells for rapid and efficient recovery, we analyzed the
      ribosome content of carbon-starved Vibrio sp. strain S14 cells. By using direct
      chemical measurements of the amounts of ribosomal particles in carbon-starved
      cultures, we demonstrated that ribosomes were lost relatively slowly (half life,
      79 h) and that they existed in large excess over the apparent demand for protein
      synthesis. After 24 h of starvation the total rate of protein synthesis was 2.3%
      of the rate during growth, and after 3 days this rate was 0.7% of the rate during
      growth; the relative amounts of ribosomal particles at these times were 81 and
      52%, respectively. The ribosome population consisted of 90% 70S monoribosomes,
      and no polyribosomes were detected in the starved cells. The 70S monoribosomes
      were responsible for the bulk of the protein synthesis during carbon starvation;
      some activity was also detected in the polyribosome size region on sucrose
      density gradients. We suggest that nongrowing carbon-starved Vibrio sp. strain
      S14 cells possess an excess protein synthesis capacity, which may be essential
      for their ability to immediately initiate an upshift program when substrate is
      added.

PMID- 1383196
TI  - Species-specific epitopes exist on the cytoplasmic amino-terminal domain of
      erythrocyte band 3 protein.
AB  - Monoclonal antibodies (P3-9H, P3-1F, P3-2H, P3-4A, and P3-4C) to human
      erythrocyte band 3 were produced using human erythrocyte membranes as the
      immunogen. All epitopes defined by these antibodies were found on the amino
      terminal cytoplasmic domain of erythrocyte band 3. The antibodies crossreacted
      variously with erythrocyte band 3 of primates (chimpanzee, orangutan, Rhesus
      monkey, Japanese monkey, spider monkey, and capuchin monkey) in enzyme-linked
      immunosorbent assay. P3-9H did not crossreact with erythrocyte band 3 of any
      primate examined; P3-1F crossreacted only with that of chimpanzee; P3-2H
      crossreacted with erythrocyte band 3 of chimpanzee, spider monkey, and capuchin
      monkey; and P3-4A and P3-4C crossreacted with erythrocyte band 3 of all primates
      examined. These results suggest that evolutional changes in primates are
      accumulated in the amino-terminal cytoplasmic domain of band 3 and that species
      specific epitopes exist on this domain.

PMID- 1383197
TI  - Structural aspects of the gastric H,K-ATPase.
AB  - The gastric H,K-ATPase is an alpha, beta heterodimer. The large catalytic subunit
      is composed, in the case of the hog enzyme, of 1033 amino acids, whereas the beta
      subunit is composed of about 291 amino acids and is heavily glycosylated. The
      membrane topology of the alpha subunit is difficult to predict using hydropathy
      analysis. Tryptic hydrolysis of intact, inside out vesicles followed by cysteine
      labelling with fluorescein-5-maleimide provided experimental evidence for an 8
      membrane spanning model for the alpha subunit, between residues 104 and 162
      (M1/M2), 291 and 358 (M3/M4), 776 and 835 (M5/M6), and 853 and 946 (M7/M8). No
      evidence was found for a pair of segments (M9/M10) towards the C terminal end of
      the molecule, contrary to predictions for the Na,K- and Ca-ATPases. Iodination of
      intact vesicles followed by carboxypeptidase Y cleavage of the C terminal
      tyrosines showed that the C terminal end of the alpha subunit was cytoplasmic.
      The epitope for antibody 146 was extracytoplasmic and located between residues
      871 to 874 between M7/M8. The binding site of the K competitive imidazo-pyridine,
      SCH28080, was to the extracytoplasmic loop between M1 and M2, whereas the binding
      of the covalent SH reagent generated from acid activation of omeprazole in acid
      transporting vesicles was to 2 cysteines at positions 813 (or 822) and 892
      predicted to be in the extracytoplasmic loops connecting M5/M6 and M7/M8,
      respectively. The beta subunit was only hydrolysed in broken vesicles. A fragment
      beginning at position 236 was liberated under these conditions only in the
      presence of reducing agents, showing that cysteine 210 and 263 were disulfide
      linked.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383198
TI  - Lectin domain peptides from selectins interact with both cell surface ligands and
      Ca2+ ions.
AB  - Selectins are receptors that mediate leukocyte adhesion to platelets or
      endothelial cells through Ca(2+)-dependent interactions with cell surface
      oligosaccharides. We found that peptides corresponding to residues 23-30, 54-63,
      and 70-79 of the N-terminal lectin domain of P-selectin inhibited leukocyte
      adhesion to P-selectin. Peptides corresponding to the homologous 23-30 and 54-63
      regions of E-selectin and L-selectin also prevented cell binding to P-selectin.
      Immobilized albumin conjugates of the three P-selectin peptides supported
      adhesion of myeloid cells and certain other cells expressing fucosylated
      oligosaccharides. Ca2+ was required for optimal cell adhesion to the conjugates
      containing the 23-30 and 54-63 sequences. Furthermore, Ca2+ interacted with the
      23-30 and 54-63 peptides of all three selectins, as detected by changes in
      intrinsic fluorescence emission intensity. These data suggest that residues
      contained within the 23-30 and 54-63 regions of the selectins represent contact
      sites for carbohydrate structures on target cells. Furthermore, binding of Ca2+
      to these sequences may directly enhance their ability to interact with cell
      surface ligands.

PMID- 1383199
TI  - Facilitated transport of methotrexate polyglutamates into lysosomes derived from
      S180 cells. Further characterization and evidence for a simple mobile carrier
      system with broad specificity for homo- or heteropeptides bearing a C-terminal
      glutamyl moiety.
AB  - Studies are presented further characterizing a facilitative system transporting
      methotrexate (MTX) polyglutamates into lysosomes derived from S180 cells. Initial
      influx of [3H]MTX + G1 (MTX with 1 additional glutamyl residue) exhibited a
      slightly alkaline pH optimum (pH 7.7) and was moderately temperature-dependent
      (Q10 27-37 degrees C = 3.1 +/- 0.1). An analysis of the kinetics of
      intralysosomal accumulation of [3H]MTX + G1 showed saturation kinetics for
      initial influx, but linear kinetics for the steady-state level of exchangeable
      [3H]MTX + G1 at different external concentrations of [3H]MTX + G1. In addition,
      the system exhibited substantial directional asymmetry with respect to the
      interaction with MTX + G1 during influx and efflux. Accelerated homo- and
      heteroexchange diffusion was demonstrated for influx of [3H]MTX + G1, while
      decelerated homoexchange diffusion was demonstrated for efflux of [3H]MTX + G1
      following trans-positioning of MTX + G1 or glutamyl-gamma-glutamate in the
      opposite compartment. These observations were consistent with a single mobile
      carrier system mediating influx and efflux of this polyglutamate. Based upon an
      analysis of competitive interactions with [3H] MTX + G1, this system displayed
      specificity for MTX-gamma-glutamates, folyl-gamma-polyglutamates, alpha- or gamma
      glutamyl peptides and heteropeptides bearing a C-terminal gamma-glutamate but not
      for MTX or glutamate, themselves. Among polyglutamates, gamma-glutamyl chain
      length was not a significant factor for transport except in the case of MTX
      polyglutamates. Overall, our results appear to delineate in the lysosomal
      membrane a simple mobile carrier system with broad specificity for folyl- or non
      folyl-bearing peptides responsible for the transport of MTX polyglutamates.

PMID- 1383201
TI  - Cloning and characterization of human cyclin D3, a cDNA closely related in
      sequence to the PRAD1/cyclin D1 proto-oncogene.
AB  - Cyclins regulate cell cycle progression by complexing with and activating cdc2 or
      related kinases. PRAD1/cyclin D1 is a recently discovered putative oncogene in
      several types of human tumors and may regulate G1-S phase progression. We have
      cloned a related human cDNA, called cyclin D3, from a placental cDNA library by
      cross-hybridization with PRAD1. In synchronized HeLa cells, the mRNA levels of
      PRAD1 and cyclin D3 were regulated reciprocally through the cell cycle: cyclin D3
      mRNA levels peaked in S phase, where PRAD1 mRNA was lowest in S. In normal human
      mammary epithelial (70N) cells synchronized by growth factor deprivation and
      subsequent growth factor stimulation, PRAD1 expression peaked in G1 and declined
      before S phase, while cyclin D3 expression rose later in G1 and remained elevated
      in S. Therefore, the close relationship (53.1% identity) between PRAD1 and cyclin
      D3 does not necessarily imply redundant functions of these candidate G1 cyclins;
      they may have distinct roles in progression from G1 through S phase.

PMID- 1383200
TI  - The adhesion molecule on glia (AMOG/beta 2) and alpha 1 subunits assemble to
      functional sodium pumps in Xenopus oocytes.
AB  - The adhesion molecule on glia, AMOG, an integral cell surface glycoprotein highly
      expressed by cerebellar astrocytes and involved in neuron to astrocyte adhesion
      and granule neuron migration (Antonicek, H., Persohn, E., and Schachner, M.
      (1987) J. Cell Biol. 104, 1587-1595) has been identified as a beta 2 subunit
      isoform of the mouse sodium pump (Gloor, S., Antonicek, H., Sweadner, K.J.,
      Pagliusi, S., Frank, R., Moos, M., and Schachner, M. (1990) J. Cell Biol. 110,
      165-174). Here we demonstrate that AMOG/beta 2 expressed by cRNA injection in
      Xenopus oocytes is capable of combining with endogenous Xenopus alpha 1 subunits
      or coexpressed Torpedo alpha 1 subunits to yield a functional alpha 1/AMOG sodium
      pump isozyme. Determinations of the number of ouabain binding sites and ouabain
      sensitive 86Rb+ uptake suggest that the alpha 1/AMOG isozyme has slightly lower
      maximum transport rate and apparent affinity for external K+ than the alpha
      1/beta 1 isozyme. Immunoprecipitation of alpha 1/AMOG complexes from digitonin
      extracts of [35S]methionine-labeled oocytes with a monoclonal anti-AMOG antibody
      provides direct evidence for a stable association between AMOG and the alpha 1
      subunits of Xenopus and Torpedo.

PMID- 1383202
TI  - Identification of the Ca(2+)-independent endocytic hyaluronan receptor in rat
      liver sinusoidal endothelial cells using a photoaffinity cross-linking reagent.
AB  - The Ca(2+)-independent endocytic hyaluronan (HA) receptor in rat liver sinusoidal
      endothelial cells (LECs) was identified using a novel cross-linking derivative of
      HA. The heterobifunctional, photoactivatable, reducible reagent sulfosuccinimidyl
      2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD) was coupled to the
      terminal amino group of uniquely modified HA-amine oligosaccharides (M(r)
      approximately 60,000) and subsequently iodinated. 125I-ASD-HA bound to cultured
      LECs with similar specificity and affinity as a previously characterized 125I-HA
      amine/Bolton-Hunter adduct. Permeabilized LECs were incubated with 125I-ASD-HA
      with 10 mM EGTA and photolysed with UV light. Detergent extracts were reduced to
      release the HA oligosaccharides and radiolabeled proteins were analyzed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Two
      polypeptides were consistently and equally labeled at M(r) = 175,000 and 166,000.
      Photoaffinity labeling of these two proteins was virtually identical in cultured
      LECs or membranes and was competed greater than 90% with a 100-fold excess of HA.
      As with the previously characterized bona fide LEC HA receptor, cross-linking was
      also competed by chondroitin sulfate and heparin, but less efficiently by
      chondroitin and not with galacturonan. We conclude that the Ca(2+)-independent
      LEC HA receptor is composed of at least two polypeptides of M(r) approximately
      175,000 and 166,000 and may exist as a heterodimer of M(r) approximately 340,000.
      We also conclude that the LEC HA receptor is distinct from the CD44 family of HA
      binding proteins.

PMID- 1383204
TI  - Spectral characterization of brain and macrophage nitric oxide synthases.
      Cytochrome P-450-like hemeproteins that contain a flavin semiquinone radical.
AB  - Nitric oxide (NO) is synthesized in mammals where it acts as a signal molecule
      for neurotransmission, vasorelaxation, and cytotoxicity. The NO synthases
      isolated from brain and cytokine-activated macrophages are FAD- and FMN
      containing flavoproteins that display considerable sequence homology to NADPH
      cytochrome P-450 reductase. However, the nature of their catalytic centers is
      unknown. We have found that both isoenzymes contain 2 mol of iron-protoporphyrin
      IX/mol of enzyme homodimer. The optical and EPR spectroscopic properties of the
      heme groups were found to be remarkably similar to those of high-spin cytochrome
      P-450. The heme iron in the resting NO synthase is ferric and five-coordinate
      with a cysteine thiolate as the proximal axial ligand. In addition, the EPR
      spectra of the resting NO synthases contained a free radical signal attributable
      to a bound flavin semiquinone that appeared to interact magnetically with the
      ferric heme iron. NO production was inhibited by carbon monoxide, implying a role
      for the heme groups in catalysis.

PMID- 1383203
TI  - Escherichia coli topoisomerase III-catalyzed cleavage of RNA.
AB  - Relaxation of superhelical DNA by Escherichia coli topoisomerase III (Topo III)
      was inhibited by the inclusion of tRNA in the reaction mixture. Investigation of
      the basis of this inhibition revealed that Topo III could bind RNA and establish
      a cleavage-religation equilibrium. The addition of SDS to these reaction mixtures
      induced cleavage of the RNA by Topo III. The nucleotide sequences of RNA and DNA
      cleavage sites were identical, although cleavage site preference differed. Thus,
      the possibility that Topo III can pass strands of RNA as well as strands of DNA
      must be considered in accounting for the role of this enzyme in nucleic acid
      metabolism.

PMID- 1383205
TI  - Thapsigargin defines the roles of cellular calcium in secretagogue-stimulated
      enzyme secretion from pancreatic acini.
AB  - In the present study we used thapsigargin (TG), an inhibitor of microsomal
      calcium ATPase, to evaluate the roles of free cytoplasmic calcium and
      intracellular stored calcium in secretagogue-stimulated enzyme secretion from rat
      pancreatic acini. Using microspectrofluorimetry of fura-2-loaded pancreatic
      acini, we found that TG caused a sustained increase in free cytoplasmic calcium
      by mobilizing calcium from inositol 1,4,5-trisphosphate-sensitive intracellular
      stores and by increasing influx of extracellular calcium. TG also caused a small
      increase in basal amylase secretion, inhibited the stimulation of amylase
      secretion caused by secretagogues that increase inositol 1,4,5-trisphosphate, and
      potentiated the stimulation of amylase secretion caused by 12-O
      tetradecanoylphorbol-13-acetate or secretagogues that increase cyclic adenosine
      3',5'-monophosphate. Bombesin, which like TG increased free cytoplasmic calcium,
      also potentiated the stimulation of amylase secretion caused by secretagogues
      that increase cyclic adenosine 3',5'-monophosphate, but did not inhibit the
      stimulation of amylase secretion caused by secretagogues that increase inositol
      1,4,5-trisphosphate. Finally, TG inhibited the sustained phase of cholecystokinin
      stimulated amylase secretion and potentiated the time course of vasoactive
      intestinal peptide-stimulated amylase secretion. The present findings indicate
      that stimulation of amylase secretion by secretagogues that increase inositol
      1,4,5-trisphosphate does not depend on increased free cytoplasmic calcium per se.
      In contrast, TG-induced potentiation of the stimulation of secretagogues that
      increase cellular cyclic adenosine 3',5'-monophosphate appears to result from
      increased free cytoplasmic calcium per se.

PMID- 1383206
TI  - Functional reconstitution of a chloride channel protein from bovine trachea.
AB  - We characterized the electrophysiological properties of a chloride channel
      protein isolated from bovine trachea after incorporation into planar lipid
      bilayers, and studied the effects of thiol-modulating agents on channel
      regulation both in bilayers and vesicular iodide uptake studies. Our experiments
      showed that this protein formed perfectly anion-selective channels in the
      bilayer, with an anion permeability sequence of I- (2.1) > NO3- (1.7) > Br- (1.2)
      > Cl- (1.0). The conductance of this channel was 25-30 picosiemens in 150 mM Cl-,
      and saturated with increasing chloride concentration. This channel could be
      completely inhibited by 4,4'-bis(isothiocyano)-2,2'-stilbenedisulfonate.
      Immunoblot analysis, using polyclonal antibodies (anti-p38), revealed one major
      band at 140 kDa. Upon reduction with dithiothreitol, 64- and 38-kDa polypeptides
      were observed. Functional experiments showed that reduction was accompanied by
      loss of 125I- uptake and single-channel activity. In the presence of
      dithiothreitol, only the low molecular mass protein forms (64 and 38 kDa) were
      detected by anti-p38 antibodies on Western blots. Cross-linking of S-S bonds with
      Cu(2+)-o-phenanthroline led to activation of chloride channels in vesicles and
      bilayers. Over-aggregation of chloride channels by this S-S cross-linking reagent
      caused inhibition of 125I- uptake by 80-100% and the abolishment of single
      channel activity. We propose that the native chloride channel from bovine trachea
      can exist in vivo in different structural and functional forms depending upon its
      thiol-disulfide oxidation reduction status. The oxidized form has a molecular
      mass of 140 kDa and represents a fully active chloride channel. Inactivation of
      this channel might occur by over-aggregation of protein subunits, or by
      dissociation of the 140-kDa subunit by disulfide bond reduction.

PMID- 1383207
TI  - Heterodimeric structure of the spider toxin omega-agatoxin IA revealed by
      precursor analysis and mass spectrometry.
AB  - We report the first molecular characterization of a precursor sequence for a
      small, Ca2+ channel blocking, peptide spider toxin, omega-agatoxin IA. By
      integrating information generated from a molecular genetic approach using
      agatoxin cDNAs with data provided from mass spectrometry of the mature toxin, we
      were able to deduce the likely mechanisms by which the toxin precursor peptide is
      processed to its mature heterodimeric form. A particularly interesting feature of
      the prepropeptide is the occurrence of two glutamate-rich sequences interposed
      between the signal sequences, the major peptide toxin, and the minor toxin
      peptide. Excision of the more distal glutamate-rich region appears to be signaled
      by flanking arginine residues but likely occurs only after a disulfide linkage
      has formed between the major and minor chains of the mature toxin. Our molecular
      genetic approach toward characterizing this toxin will allow us to quickly
      generate a series of spider sequences from which mature toxin structures can be
      deduced and eventually expressed. Additionally, this approach will provide
      insights into the evolutionary divergence observed among spider peptide toxins.

PMID- 1383208
TI  - Secretagogue-induced mobilization of an intracellular Mg2+ pool in rat sublingual
      mucous acini.
AB  - The regulation of the intracellular free Mg2+ concentration ([Mg2+]i) was
      monitored in rat sublingual mucous acini using dual wavelength microfluorometry
      of the Mg(2+)-sensitive dye mag-fura-2. Acini attached to coverslips and
      superfused continuously with a Mg(2+)-containing medium (0.8 mM) have a steady
      state [Mg2+]i of 0.35 +/- 0.01 mM. Adjusting the extracellular Mg2+ concentration
      to 0 and 10 mM or removing extracellular Na+ did not alter the resting [Mg2+]i.
      Stimulation with the Ca(2+)-mobilizing, muscarinic agonist, carbachol, induced a
      sustained increase in [Mg2+]i (approximately 50%; t1/2 < 20 s; Kd approximately
      1.5 microM), the magnitude and the duration of which were unchanged in Mg(2+)
      depleted medium indicating that the rise in [Mg2+]i was generated by Mg2+ release
      from an intracellular Mg2+ pool. Forskolin, which increases the intracellular
      cAMP content, produced a small, transient increase in the [Mg2+]i (< 10%).
      Muscarinic stimulation in a Ca(2+)-free medium blunted the initial increase in
      [Mg2+]i by approximately 50%, whereas the sustained increase in [Mg2+]i was lost.
      When the muscarinic-induced increase in [Ca2+]i was blocked by 8
      (diethylamino)octyl 3,4,5-trimethoxybenzoate, an inhibitor of the agonist
      sensitive intracellular Ca2+ release pathway, both the initial and the sustained
      phases of the increase in [Mg2+]i were virtually eliminated. Thapsigargin and 2,5
      di-(terbutyl)-1,4-benzohydroquinone, which increase [Ca2+]i by inhibiting
      microsomal Ca(2+)-ATPase, caused a dramatic increase in [Mg2+]i. Stimulation in a
      Na(+)-free medium or in the presence of bumetanide, an inhibitor of Na+/K+/2Cl-
      cotransport, blunted the agonist-induced rise in [Mg2+]i (approximately 50%),
      whereas ouabain, a Na+,K(+)-ATPase inhibitor, had no significant effect. FCCP
      (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), a mitochondrial uncoupler,
      mobilized an intracellular Mg2+ pool as well. The carbachol-induced increase in
      [Mg2+]i was markedly inhibited by FCCP (approximately 80%), suggesting that the
      same pool(s) of Mg2+ were primarily involved. The above results provide strong
      evidence that Ca(2+)-mobilizing agonists increase cytoplasmic free [Mg2+] by
      releasing an intracellular pool of Mg2+ that is associated with a rise in the
      [Na+]i.

PMID- 1383209
TI  - A potent enhancer made of clustered liver-specific elements in the transcription
      control sequences of human alpha 1-microglobulin/bikunin gene.
AB  - alpha 1-Microglobulin (A1M) and bikunin are plasma proteins which are present
      both as free molecules and as complexes with either IgA heavy chains for A1M or
      the H1, H2, and H3 heavy chains of the inter-alpha-inhibitor family for bikunin.
      Mature A1M and bikunin originate from the cleavage of an A1M/bikunin precursor
      (ABP) synthesized from a single gene with liver-specific expression. Five
      kilobases of the 5'-flanking region of the human ABP gene were sequenced.
      Deletion mutants of this region subcloned upstream of a CAT reporter gene were
      transfected into HepG2 hepatoma cells. A segment covering the -2.7- to -2.8-kb
      area is required for full activity of the ABP gene. This segment contains a
      cluster of six elements (boxes 1-6, 5' to 3') which are potential binding sites
      for the liver-enriched trans-acting factors HNF-1, HNF-4, HNF-3, HNF-1, HNF-3,
      and HNF-4, respectively. This cluster enhances the activity of heterologous
      minimal promoters in a position- and distance-independent fashion in HepG2 cells.
      This enhancer activity is restricted to liver cells as the cluster is unable to
      activate promoters in Chinese hamster ovary (CHO) or HeLa cells. By band-shift
      experiments we have shown that the liver-enriched transcription factors HNF-1, or
      HNF-3, do bind to boxes 1 and 4, or 3, respectively. The combination of a weak
      promoter and a strong distant and liver-specific enhancer distinguishes the ABP
      gene from most other plasma protein genes expressed in hepatocytes.

PMID- 1383210
TI  - Apolipoprotein AI expression and high density lipoprotein distribution in
      transgenic mice during development.
AB  - The developmental changes in apoAI expression in human apolipoprotein AI (apoAI)
      transgenic and nontransgenic control mice and the effect of these changes on high
      density lipoprotein (HDL) sizes were investigated. Results demonstrated that both
      human and mouse apoAI mRNA levels sharply increased following delivery and then
      decreased prior to weaning. Unlike the changes in apoAI mRNA, plasma apoAI
      concentration and HDL mass increased following delivery and remained elevated as
      the animals matured. In these animals, parallel increases in plasma apoAI and HDL
      mass with development were accompanied by increases in HDL particle sizes.
      Control mice demonstrated a monodisperse population of particles that increased
      in particle size from 7.5 nm (at 2 days prior to birth) to 9.8 nm (at 13 days
      after birth). The latter is similar to the adult HDL size and distribution.
      Transgenic mice, unlike controls, exhibited several distinct HDL populations,
      which also increased in size as animals matured. These results suggest that post
      transcriptional factors are important in regulating apoAI plasma levels and that
      developmental changes in plasma apoAI concentrations are associated with changes
      in HDL size distribution.

PMID- 1383211
TI  - Differential sorting of lutropin and the free alpha-subunit in cultured bovine
      pituitary cells.
AB  - The glycoprotein hormones lutropin (LH) and follitropin (FSH) are both
      synthesized by gonadotrophs in the anterior pituitary but are stored in separate
      secretory granules prior to secretion. Despite having highly homologous beta
      subunits and alpha-subunits with the identical amino acid sequence, the Asn
      linked oligosaccharides on LH terminate with SO4-GalNAc while those on FSH
      terminate with sialic acid-Gal. In addition to LH and FSH, gonadotrophs secrete
      uncombined (free) alpha-subunit which bears the same sulfated oligosaccharides as
      LH. We have examined the synthesis and secretion of LH and free alpha-subunit in
      primary cultures of bovine pituitary cells in order to determine if the sulfated
      oligosaccharides have any impact on sorting. Our results show that newly
      synthesized free alpha-subunit is secreted exclusively via the constitutive
      pathway with a t1/2 of 1.8 h and is never found in dense-core secretory granules.
      In contrast, LH dimer is secreted by both the constitutive and the regulated
      pathways. Constitutive secretion and arrival in a dense secretory granule both
      occur with t1/2 values of 1-1.5 h for newly synthesized LH. Sulfation occurs
      immediately prior to arrival of LH in the secretory granule and is followed by a
      period of 1-1.5 h before the LH-containing granules become sensitive to release
      by gonadotropin releasing hormone. As a result the t1/2 for LH secretion in the
      presence of gonadotropin releasing hormone is 3.5 h. Sulfation of the free alpha
      subunit oligosaccharides is not, therefore, sufficient to direct the alpha
      subunit to secretory granules, and the information required for directing LH to
      granules must reside either in the beta-subunit or the alpha beta-complex.

PMID- 1383212
TI  - Beta-adrenergic regulation of a myocardial actin gene via a cyclic AMP
      independent pathway.
AB  - The skeletal alpha-actin gene encodes a major component of the embryonic cardiac
      sarcomere that is strongly and selectively re-induced during beta-adrenoceptor
      mediated hypertrophy in neonatal rat cardiac myocytes. We present evidence that
      beta-adrenergic induction of this gene is mediated, not by cAMP, but by a calcium
      dependent pathway involving ryanodine-sensitive calcium stores. Nifedipine
      induced blockade of the plasma membrane L-type calcium entry channel prevented
      induction of skeletal alpha-actin mRNA by isoproterenol. Activation of calcium
      entry by the dihydropyridine agonist Bay K8644 independently induced skeletal
      alpha-actin mRNA, as did cholera toxin-mediated activation of Gs. Induction of
      skeletal alpha-actin mRNA by compounds that directly elevate cAMP was weak
      relative to their effects on other cAMP-dependent phenomena and required calcium
      entry. In addition, selective inhibition of protein kinase A with KT5720 did not
      block beta-adrenergic induction of skeletal alpha-actin. Calcium ionophore A23187
      did not induce skeletal actin, but prevented its induction by isoproterenol.
      Ryanodine had bimodal effects: 10(-10) M ryanodine induced skeletal alpha-actin
      mRNA, whereas 10(-6) M ryanodine prevented skeletal actin induction by beta
      adrenergic stimuli. We postulate that beta-adrenergic stimulation of skeletal
      alpha-actin mRNA requires G-protein-coupled calcium channel activation and
      compartmentalized calcium release in a manner independent of the cAMP/protein
      kinase A signal pathway.

PMID- 1383213
TI  - Transcriptional regulation and increased functional expression of the inositol
      trisphosphate receptor in retinoic acid-treated HL-60 cells.
AB  - The inositol trisphosphate (InsP3) receptor is an essential regulator of
      intracellular calcium in many cells including chemoattractant- and cytokine
      stimulated neutrophils and differentiated promyelocytic leukemic (HL-60) cells.
      We examined the expression and function of the InsP3 receptor and the
      transcriptional regulation of the InsP3 receptor gene in HL-60 cells and in HL-60
      cells treated for 1-5 days with 1 microM retinoic acid. Radioligand binding
      studies using membranes from control and retinoic acid-treated HL-60 cells showed
      that the Bmax of InsP3 receptor increased progressively from 0.24 to 0.69 pmol/mg
      protein during 5 days retinoic acid treatment with no change in KD (19 nM).
      During this period, maximal InsP3-stimulated Ca2+ mobilization increased 2-3
      fold. InsP3 receptor mRNA was present at low levels in HL-60 cells but was
      increased significantly after treatment with retinoic acid, reaching maximal
      levels of approximately 4-fold greater than untreated cells after 4 days
      treatment with retinoic acid. Nuclear run-on assays indicated that the elevated
      steady state level of InsP3 receptor mRNA in retinoic acid-treated HL-60 cells
      was primarily the result of enhanced transcription of the InsP3 receptor gene.
      Furthermore, the transcriptional enhancing effect of retinoic acid was seen in
      the presence of cycloheximide, suggesting that the InsP3 receptor gene is
      directly regulated by retinoic acid. The studies also demonstrate that the InsP3
      receptor mRNA is rapidly degraded in HL-60 cells by a mechanism that also
      requires protein synthesis.

PMID- 1383214
TI  - Cloning and expression of the Gal beta 1, 3GalNAc alpha 2,3-sialyltransferase.
AB  - Sequence information obtained by NH2-terminal sequence analysis of two molecular
      weight forms (45 and 48 kDa) of the porcine Gal beta 1,3GalNAc alpha 2,3
      sialyltransferase was used to clone a full-length cDNA of the enzyme. The cDNA
      sequence revealed an open reading frame coding for 343 amino acids and a putative
      domain structure consisting of a short NH2-terminal cytoplasmic domain, a signal
      anchor sequence, and a large COOH-terminal catalytic domain. This domain
      structure was confirmed by construction of a recombinant sialyltransferase in
      which the cytoplasmic domain and signal-anchor sequence of the enzyme was
      replaced with the cDNA of insulin signal sequence. Expression of the resulting
      construct in COS-1 cells produced an active sialyltransferase which was secreted
      into the medium in soluble form. Comparison of the cDNA sequence of the
      sialyltransferase with GenBank produced no significant homologies except with the
      previously described Gal beta 1,4GlcNAc alpha 2,6-sialyltransferase. Although the
      cDNA sequences of these two enzymes were largely nonhomologous, there was a 45
      amino acid sequence which exhibited 65% identity. This observation suggests that
      the two sialyltransferases were derived, in part, from a common gene.

PMID- 1383215
TI  - Signal transduction by the cytoplasmic domains of Fc epsilon RI-gamma and TCR
      zeta in rat basophilic leukemia cells.
AB  - The gamma subunit of the high affinity IgE receptor, Fc epsilon RI, is a member
      of a family of proteins which form disulfide-linked dimers. This family also
      includes the zeta- and eta-chains of the T cell receptor. Engagement of Fc
      epsilon RI activates src-related protein tyrosine kinases in basophils and mast
      cells. However, the role of individual subunits of Fc epsilon RI in this
      activation is still not known. In an effort to determine the function of Fc
      epsilon RI-gamma, we used chimeric proteins containing the extracellular and
      transmembrane domains of the alpha chain of the human interleukin 2 receptor
      (Tac) and the cytoplasmic domains of either T cell receptor-zeta or Fc epsilon RI
      gamma. We show that while cross-linking of the Tac chimeras in the rat basophilic
      leukemia cell line RBL-2H3 resulted in the tyrosine phosphorylation of a subset
      of proteins and a portion of the degranulation normally observed after Fc epsilon
      RI-mediated stimulation, no detectable activation of p56lyn or pp60c-src was
      observed. In contrast, an apparent transient deactivation of these two kinases
      was observed after Tac chimera cross-linking. These observations suggest that Fc
      epsilon RI-gamma is responsible for some, but not all, of the signaling that
      occurs after engagement of its receptor, and that other receptor subunits may
      also play important roles in this signaling process.

PMID- 1383216
TI  - Comparison of src-family cDNAs reveals distinct mechanisms underlying focus
      formation in transfected fibroblasts.
AB  - Despite the intensive study of both cellular transformation and src-family
      protein-tyrosine kinases, there have been no direct comparisons of transforming
      potency for normal members of this gene-family. In this study, the focus-forming
      activity of normal c-src, fyn, and lck cDNAs were compared in NIH 3T3 cell
      transfection assays. Focus formation was studied quantitatively, and individual
      foci were analyzed for phosphotyrosine content and expression of appropriate
      translational products. Each foci arising from c-src transfectants had a marked
      increase in phosphotyrosine content, and the majority of these foci expressed a c
      src protein with an aberrant carboxyl terminus. Foci derived from lck
      transfectants also had a marked increase in phosphotyrosine content, and some
      foci expressed a lck protein with an aberrant carboxyl terminus. In contrast,
      foci from fyn-transfected cells were not distinguished from G418-selected mass
      cultures in terms of total phosphotyrosine content or expression of p59fyn. These
      studies support the previously published concept that overexpression of the
      normal fyn protein contributes to focus formation in transfected NIH 3T3 cells
      but suggest that the focus-forming activity observed after c-src or lck
      transfections is frequently attributable to mutational events. Because lck
      mutations have not been previously described in transformed foci, we
      characterized the lck transcript expressed in two foci and identified a novel
      point mutation that encodes a lck protein with increased in vivo kinase and focus
      forming activity.

PMID- 1383217
TI  - Calcitonin gene-related peptide inhibits interleukin 2 production by murine T
      lymphocytes.
AB  - Evidence from the literature suggests that the nervous and the immune systems
      closely interact via neuromediators, which affect the immune system, and
      cytokines, which control nerve cell growth and activity. Calcitonin gene-related
      peptide (CGRP) is a neuropeptide that has been identified in numerous tissues
      including immune organs and inhibits the proliferation of spleen cells. We
      investigated whether CGRP altered the function of T lymphocytes. We present
      evidence that CGRP induces a dose-dependent cAMP accumulation in interleukin 2
      producing TH1 cells and inhibits their production of interleukin 2. These effects
      are prevented by CGRP8-37, a CGRP antagonist that is missing the first 7 amino
      acids. This CGRP-mediated inhibition of interleukin 2 production is accompanied
      by a decrease in interleukin 2 mRNA accumulation. CGRP also inhibits the
      accumulation of mRNA coding for tumor necrosis factor-alpha and -beta and
      interferon-gamma. Thus, we have identified one mechanism by which CGRP inhibits
      the proliferation of spleen cells.

PMID- 1383218
TI  - A membrane-bound monoheme cytochrome c551 of a novel type is the immediate
      electron donor to P840 of the Chlorobium vibrioforme photosynthetic reaction
      center complex.
AB  - A photosynthetic reaction center complex has been isolated from the green sulfur
      bacterium Chlorobium vibrioforme. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis reveals polypeptides with apparent molecular masses of 80, 40,
      18, 15, 9, and 6 kDa. Only the 18-kDa polypeptide is stained with 3,3',5,5'
      tetramethylbenzidine, a heme-specific reagent. Oxidized minus reduced difference
      spectra show the presence of approximately one heme/P840 and the presence of a
      cytochrome c551. Flash photolysis of P840 was followed by rereduction of P840+
      and oxidation of cytochrome c551, both with a biphasic kinetic with t1/2 values
      of 7 and 50 microseconds. Using oligonucleotide probes derived from an N-terminal
      amino acid sequence of the 18-kDa polypeptide, a genomic clone was isolated. The
      sequence of the gene, which we designate cycA, predicts a single heme binding
      site (Cys-Asn-Lys-Cys-His). The 621-base pair open reading frame encodes an
      apoprotein of 22,858 Da with three predicted membrane-spanning alpha-helices. No
      extensive sequence similarity is found to other cytochromes. Northern blotting
      indicates that the cycA gene is transcribed as a monocistronic mRNA. Southern
      blotting shows the presence of only one cycA gene in the C. vibrioforme and
      Chlorobium tepidum genomes. The unique membrane-bound monoheme cytochrome c551 of
      C. vibriforme is assigned to a new class of c-type cytochromes. The implications
      for the current view of evolution of photosynthetic reaction center complexes are
      discussed.

PMID- 1383219
TI  - Phosphorylation of carbovir enantiomers by cellular enzymes determines the
      stereoselectivity of antiviral activity.
AB  - Two enantiomers of carbovir, a carbocyclic analog of 2',3'-dideoxyguanosine, were
      compared with respect to their phosphorylation and the phosphorylation of their
      nucleotides by mammalian enzymes. 5'-Nucleotidase catalyzed the phosphorylation
      of (-)-carbovir, which is active against HIV (human immunodeficiency virus), but
      did not phosphorylate (+)-carbovir. (-)-Carbovir monophosphate was 7,000 times
      more efficient as a substrate for GMP kinase than was (+)-carbovir monophosphate.
      Pyruvate kinase, phosphoglycerate kinase, and creatine kinase phosphorylated both
      enantiomers of carbovir diphosphate at similar rates. Nucleoside-diphosphate
      kinase preferentially phosphorylated the (-)-enantiomer. Both enantiomers of
      carbovir triphosphate were substrates and alternative substrate inhibitors of HIV
      reverse transcriptase. Thus, the contrasting HIV-inhibitory activities of
      carbovir enantiomers were due to differential phosphorylation by cellular enzymes
      and not due to enantioselectivity of HIV reverse transcriptase.

PMID- 1383220
TI  - Polynucleotidyl transfer reactions in transpositional DNA recombination.

PMID- 1383221
TI  - Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production
      by keratinocytes. Potential role for nitric oxide in the regulation of wound
      healing.
AB  - In the skin, wounding initiates a complex array of physiological processes
      mediated by growth factors and inflammatory mediators which stimulate tissue
      repair and protect against infection. We report that primary cultures of human
      keratinocytes and a mouse keratinocyte cell line respond to the inflammatory
      stimuli gamma-interferon and lipopolysaccharide or tumor necrosis factor-alpha by
      producing nitric oxide and hydrogen peroxide, two reactive mediators that are
      important in nonspecific host defense. Nitric oxide is produced by the l-arginine
      and NADPH-dependent enzyme, nitric oxide synthase. In murine keratinocytes,
      optimal enzymatic activity was found to be dependent on Ca2+ and calmodulin as
      well as on glutathione. Inflammatory mediators were also found to inhibit the
      growth of keratinocytes, an effect that could be reversed by a nitric oxide
      synthase inhibitor. Epidermal growth factor (EGF), which promotes wound healing
      by stimulating cellular proliferation, was found to be a potent antagonist of
      reactive nitrogen and reactive oxygen intermediate production by keratinocytes.
      EGF also reversed the growth inhibitory actions of the inflammatory mediators.
      These data suggest that nitric oxide produced by keratinocytes is important in
      the control of cellular proliferation during wound healing. Our findings that EGF
      effectively regulates the production of free radicals by keratinocytes may
      represent an important pathway by which this growth factor not only stimulates
      epidermal cell proliferation but also facilitates the resolution of inflammation
      following wounding.

PMID- 1383222
TI  - Tissue distribution and cellular localization of hsp56, an FK506-binding protein.
      Characterization using a highly specific polyclonal antibody.
AB  - Heat shock protein 56 (hsp56) has been shown to be involved in two cellular
      pathways, as an immunophilin for FK506 and as a component of steroid receptor
      complexes. To help define its role in these cellular pathways, we have developed
      UPJ56, a polyclonal antibody raised against hsp56 purified from Jurkat cells. In
      Western blot experiments, hsp56 was highly expressed in rat thymus, liver, and
      spleen, with low levels in lung and muscle. In immunofluorescence experiments
      using untreated LLC-PK1 cells, fibrillar staining was seen in the cytoplasm,
      suggesting a cytoskeletal localization of hsp56. The nuclei were brightly
      stained, except for the nucleoli. Confocal microscopy demonstrated that the
      staining was present in all planes of the nucleus. These results suggest that
      hsp56 is expressed in tissues enriched in steroid receptors and is highly
      expressed in tissues involved in T cell function. Furthermore, the localization
      of hsp56 with the cytoskeleton and throughout the nucleus is consistent with its
      association with steroid receptor complexes.

PMID- 1383224
TI  - Ruthenium red inhibits the binding of calcium to calmodulin required for enzyme
      activation.
AB  - The Ca(2+)-calmodulin (CaM)-dependent activation of myosin light chain kinase is
      inhibited by ruthenium red competitively with respect to Ca2+, with a Ki value of
      8.6 microM. The binding of Ca2+ to CaM is inhibited by micromolar concentrations
      of ruthenium red. In the absence of Ca2+, CaM has two binding sites for ruthenium
      red with the dissociation constants of 0.36 and 8.7 microM, respectively. Ca2+
      antagonizes the binding of ruthenium red to the low-affinity site on CaM. Binding
      of ruthenium red to the high-affinity site is not affected by Ca2+. The low- and
      high-affinity sites for ruthenium red are shown to be located in the NH2-terminal
      half and the COOH-terminal half of CaM, respectively. Lower concentrations of
      ruthenium red are needed for enzyme inactivation than for the dissociation of
      enzyme-CaM-Sepharose complex, suggesting these events have different Ca2+
      requirements. Moreover, ruthenium red inhibits Ca(2+)-induced contraction of
      depolarized vascular smooth muscle in a competitive manner with respect to Ca2+.
      These results suggest that ruthenium red may be a new type of CaM antagonist that
      inhibits the binding of Ca2+ to CaM and thereby inhibits Ca(2+)-CaM-dependent
      enzymes and smooth muscle contraction competitively with respect to Ca2+.

PMID- 1383223
TI  - Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus
      oocytes and neurite retraction in PC12 pheochromocytoma cells.
AB  - Serum contains a factor that co-purifies with albumin and causes neurite
      retraction in PC12 cells, inhibits the proliferation of tumor cells in vitro, and
      activates the phosphatidylinositol/Ca2+ second messenger system in Xenopus
      oocytes and other cells. The activity of serum albumin depends on several
      lysophospholipids bound to albumin. Thin layer chromatographic analysis of the
      lipids extracted by methanol from serum albumin revealed over a dozen components,
      several of which evoked oscillatory currents in oocytes. In contrast to serum
      albumin, most of these lipids were absent in plasma, which lacks the biological
      activity. The most abundant naturally occurring active component was identified
      as stearoyl-lysophosphatidic acid. Synthetically prepared lysophosphatidates
      reproduced the biological activities of the natural serum factor. Adding
      synthetic lysophosphatidates to inactive fatty acid-free albumin restored
      activity to the albumin, making the active factor nondialyzable against aqueous
      solvents and protecting against digestion by various lipases. Since the
      biologically active lysophosphatidates were produced during blood clotting, in
      the presence of platelets, and lysophosphatidates have been shown previously to
      activate platelets, we propose that lysophosphatidates may play an important role
      in linking platelet activation to receptor-mediated tissue regeneration.

PMID- 1383225
TI  - Activation of the Na(+)-K(+)-2Cl- cotransporter in rat parotid acinar cells by
      aluminum fluoride and phosphatase inhibitors.
AB  - The bumetanide-sensitive component of pHi recovery from an NH4Cl-induced acute
      alkaline load was used as a measure of Na(+)-K(+)-2Cl- cotransport activity in
      rat parotid acini. Acinar treatment with NaF/AlCl3 (15 mM NaF plus 10 microM
      AlCl3) induced a 5-fold stimulation in the initial rate of bumetanide-sensitive
      pHi recovery. This effect was dependent on NaF concentration (K1/2 approximately
      7 mM) and was blunted in the presence of the Al3+ chelator desferal mesylate
      suggesting that it might be due to the aluminofluoride ion, AlF-4. NaF/AlCl3
      treatment did not increase acinar intracellular cAMP levels but did result in an
      increase in intracellular calcium concentration (from 87 +/- 5 to 181 +/- 2 nM)
      and in acinar cell shrinkage (12 +/- 1%). But the stimulation of the Na(+)-K(+)
      2Cl- cotransporter by NaF/AlCl3 persisted in acini which had been depleted of
      their intracellular Ca2+ stores. In these acini no effect of NaF/AlCl3 on
      intracellular calcium or cell volume was observed, indicating that stimulation of
      the cotransporter was not secondary to either of these phenomena. The effect of
      NaF/AlCl3 on the cotransporter was blocked by the protein kinase inhibitor K252a
      indicating the involvement of a protein phosphorylation event. This result is
      consistent with either NaF/AlCl3-dependent protein kinase activation or
      phosphatase inhibition. The stimulation of the cotransporter by NaF/AlCl3 was
      mimicked by the protein phosphatase inhibitor calyculin A; however, this effect
      was not blocked by K252a suggesting that a different protein kinase from that
      associated with NaF/AlCl3 may be involved. The data indicate that the Na(+)-K(+)
      2Cl- cotransporter in this tissue is under tight regulatory control, in all
      likelihood via multiple protein kinase/phosphatase systems. The physiological
      roles of these regulatory events in modulating acinar fluid secretion driven by
      the Na(+)-K(+)-2Cl- cotransporter remain to be elucidated.

PMID- 1383226
TI  - Characterization of high molecular weight FK-506 binding activities reveals a
      novel FK-506-binding protein as well as a protein complex.
AB  - The immunoregulant FK-506 potently inhibits particular calcium-associated signal
      transduction events that occur early during T-lymphocyte activation and during
      IgE receptor-mediated exocytosis in mast cells. FK-506 binds to a growing family
      of receptors termed FK-506-binding proteins (FKBPs), the most abundant being a 12
      kDa cytosolic receptor, FKBP12. To date, there is no formal evidence proving that
      FKBP12 is the sole receptor mediating the immunosuppressive effects or toxic side
      effects of FK-506. Using gel filtration chromatography as an assay for novel FK
      506-binding proteins, we identified FK-506 binding activities in extracts
      prepared from calf brain and from JURKAT cells. Both of these new activities
      comigrated with apparent molecular masses of 110 kDa. However, further
      characterization of both binding activities revealed that the two are not
      identical. The 110-kDa activity observed in brain extracts appears to be the
      FKBP12.FK-506.calcineurin (CaN) complex previously reported (Liu, J., Farmer, J.,
      Lane, W., Friedman, J., Weissman, I., and Schreiber, S. (1991) Cell 66, 807-815)
      while the 110 kDa activity observed in JURKAT cells is a novel FK-506-binding
      protein. Our characterization of the FKBP12.FK-506.CaN complex reveals a
      dependence upon calmodulin (CaM) for formation of the complex and demonstrates
      that the peptidyl-prolyl cis-trans isomerase (PPIase) activity of FKBP12 is not
      required for binding of FKBP12.FK-506 to CaN or for inhibition of CaN phosphatase
      activity. The novel FK-506-binding protein in JURKAT cells has been purified to
      homogeneity, migrates with an apparent mass of 51 kDa on denaturing gels, and has
      been termed FKBP51. Like FKBP12, FKBP51 has PPIase activity, but, unlike
      FKBP12.FK-506, FKBP51.FK-506 does not complex with or inhibit the phosphatase
      activity of, CaN. These results indicate that complex formation with CaN may not
      be a general property of the FKBPs. Peptide sequencing reveals that FKBP51 may be
      similar, if not identical, to hsp56, a component of non-transformed steroid
      receptors.

PMID- 1383227
TI  - Characterization of a Xenopus laevis ribonucleoprotein endoribonuclease.
      Isolation of the RNA component and its expression during development.
AB  - In order to facilitate studies of the assembly and transport of the site-specific
      RNase mitochondrial RNA processing (MRP) ribonucleoprotein, we have characterized
      it from Xenopus laevis cells. X. laevis RNase MRP displayed a similar spectrum of
      cleavage activity to that produced by previously isolated mammalian nuclear
      enzymes. A 277-nucleotide RNA component of the ribonucleoprotein was identified;
      the gene for the RNA was isolated, sequenced, and found to be 66 and 63% similar
      to mouse and human RNase MRP RNAs, respectively. Despite the evolutionary
      distance from its mammalian counterparts, X. laevis RNase MRP RNA contains five
      regions of homology to the mammalian RNase MRP RNA. Four of these regions
      correspond to those previously identified as conserved between RNase MRP and
      RNase P RNAs; the fifth encompasses nucleotides recently discovered to be
      sufficient for autoantigen binding. The expression and assembly of Xenopus RNase
      MRP RNA were examined in frog oocytes and developing embryos. RNase MRP RNA was
      expressed throughout oogenesis; it started to accumulate at stage I and reached a
      maximum in stage IV. During embryogenesis RNase MRP RNA expression began to
      elevate at approximately stage 22 and continued to rise through the swimming
      tadpole stage. When injected into the nucleus of mature oocytes, the X. laevis
      RNase MRP RNA gene was expressed accurately, and transcripts were packaged into
      immunoprecipitable particles.

PMID- 1383228
TI  - Identification of a tissue-specific regulatory element within the murine CD14
      gene.
AB  - We previously isolated and sequenced the 5'-flanking region of the mouse CD14
      (mCD14) gene (Matsuura, K., Setoguchi, M., Nasu, N., Higuchi, Y., Yoshida, S.,
      Akizuki, S., and Yamamoto, S. (1989) Nucleic Acids Res. 17, 2132). To define the
      regulatory elements that control expression of the mCD14 gene, we analyzed the
      structure of the 5' end of the gene, including a region further upstream of that
      determined previously. Sequentially 5'-deleted, chimeric, and point mutated
      clones were tested for the ability to stimulate chloramphenicol
      acetyltransferase. An 8-base pair sequence, TGATTCAC, at position -255, which
      resembled the consensus sequence of the 12-O-tetradecanoylphorbol-13-acetate
      responsive element (TRE), enhanced the expression of the chloramphenicol
      acetyltransferase gene in macrophage (aHINS-B3) and non-macrophage (glioblastoma
      G203 and myeloma NS1) cells. The enhancing ability of the TRE-like sequence
      (TLS), however, was markedly reduced in G203 cells but not in aHINS-B3 cells when
      the TLS was followed by the sequence immediately downstream. The TLS and sequence
      immediately downstream were capable of binding nuclear proteins which were unique
      to aHINS-B3 cells and macrophages, suggesting that these unique protein regulate
      the specific expression of the mCD14 gene. Binding of AP-1 to the TLS was also
      found in aHINS-B3 and G203 cells. Although it is uncertain whether AP-1 is
      involved in expression of the mCD14 gene, the effect of AP-1 in non-macrophage
      cells was inhibited by a nuclear protein which binds to the sequence immediately
      downstream of the TLS.

PMID- 1383229
TI  - Angiogenesis in healing autogenous flexor-tendon grafts.
AB  - On the basis of recent evidence that flexor tendon grafts may heal without the
      ingrowth of vascular adhesions, eighteen autogenous donor tendons of
      intrasynovial and extrasynovial origin were transferred to the synovial sheaths
      in the forepaws of nine dogs, and controlled passive mobilization was instituted
      early in the postoperative period. The angiogenic responses of the tendon grafts
      were determined with perfusion studies with India ink followed by cleaing of the
      tissues with the Spalteholz technique at two, four, and six weeks. A consistent
      pattern of neovascularization was noted in the donor tendons of extrasynovial
      origin. Vascular adhesions arising from the flexor digitorum superficialis and
      the tendon sheath enveloped the tendon grafts by two weeks. By six weeks, the
      vascularity of the tendon grafts of extrasynovial origin appeared completely
      integrated with that of the surrounding tissues. Examination of cross sections
      revealed that the segments of tendon had been completely vascularized by
      obliquely oriented intratendinous vessels. In contrast, the flexor tendon grafts
      of intrasynovial origin healed without ingrowth of vascular adhesions. Primary
      intrinsic neovascularization took place from the proximal and, to a lesser
      extent, distal sites of the sutures. Examination of cross sections revealed
      vessels extending through the surface layer of the tendon graft, with small
      vessels penetrating the interior of the tendons at regular intervals.

PMID- 1383230
TI  - The EGF receptor is an actin-binding protein.
AB  - In a number of recent studies it has been shown that in vivo part of the EGF
      receptor (EGFR) population is associated to the actin filament system. In this
      paper we demonstrate that the purified EGFR can be cosedimented with purified
      filamentous actin (F-actin) indicating a direct association between EGFR and
      actin. A truncated EGFR, previously shown not to be associated to the
      cytoskeleton, was used as a control and this receptor did not cosediment with
      actin filaments. Determination of the actin-binding domain of the EGFR was done
      by measuring competition of either a polyclonal antibody or synthetic peptides on
      EGFR cosedimentation with F-actin. A synthetic peptide was made homologous to
      amino acid residues 984-996 (HL-33) of the EGFR which shows high homology with
      the actin-binding domain of Acanthamoeba profilin. A polyclonal antibody raised
      against HL-33 was found to prevent cosedimentation of EGFR with F-actin. This
      peptide HL-33 was shown to bind directly to actin in contrast with a synthetic
      peptide homologous to residues 1001-1013 (HL-34). During cosedimentation, HL-33
      competed for actin binding of the EGFR and HL-34 did not, indicating that the
      EGFR contains one actin-binding site. These results demonstrate that the EGFR is
      an actin-binding protein which binds to actin via a domain containing amino acids
      residues 984-996.

PMID- 1383232
TI  - Isolation and characterization of an inhibitor of neovascularization from
      scapular chondrocytes.
AB  - An inhibitor of neovascularization from the conditioned media of scapular
      chondrocytes established and maintained in serum-free culture has been isolated
      and characterized. To determine whether this chondrocyte-derived inhibitor (ChDI)
      was capable of inhibiting neovascularization in vivo, this protein was assayed in
      the chick chorioallantoic membrane assay. ChDI was a potent inhibitor of
      angiogenesis in vivo (4 micrograms = 87% avascular zones). This inhibitor is also
      an inhibitor of fibroblast growth factor-stimulated capillary endothelial cell
      (EC) proliferation and migration, as well as being an inhibitor of mammalian
      collagenase. ChDI significantly suppressed capillary EC proliferation in a dose
      dependent, reversible manner with an IC50 (the inhibitory concentration at which
      50% inhibition is achieved) of 2.025 micrograms/ml. Inhibition by ChDI of growth
      factor-stimulated capillary EC migration was also observed using a modified
      Boyden chamber assay (IC50 = 255 ng/ml). SDS-PAGE analysis followed by silver
      staining of ChDI purified to apparent homogeneity revealed a single band having
      an M(r) of 35,550. Gel elution experiments demonstrated that only protein eluting
      at this molecular weight was anti-angiogenic. These studies are the first
      demonstration that chondrocytes in culture can produce a highly enriched, potent
      inhibitor of neovascularization which also inhibits collagenase.

PMID- 1383231
TI  - The roles of K5 and K14 head, tail, and R/K L L E G E domains in keratin filament
      assembly in vitro.
AB  - Type I and type II keratins form obligatory heterodimers, which self-assemble
      into 10-nm intermediate filaments (IFs). Like all IF proteins, they have a
      central alpha-helical rod domain, flanked by nonhelical head and tail domains.
      The IF rod is more highly conserved than head and tail, and within the rod, the
      carboxy R/K L L E G E sequence is more highly conserved than most other regions.
      Mutagenesis studies have shed some light on the roles of the head, tail, and R/K
      L L E G E sequence in 10-nm filament structure. However, interpretations have
      often been complicated in part because many of these studies have focused on
      transfected cells, where filament structure cannot be evaluated. Of the few in
      vitro assembly studies thus far conducted, comparison of keratin mutants with
      other IF mutants have often been difficult, due to the obligatory heteropolymeric
      nature of keratin IFs. In this report, we describe in vitro filament assembly
      studies on headless, tailless, headless/tailless, and R/K L L E G E truncated
      mutants of keratin 5 and its partner keratin 14. Using varying conditions of
      ionic strength and pH, we examine effects of analogous K5 and K14 mutations on
      the stability of 10-nm filament structure. Using EM, we examine effects of
      mutations on the ability of subunits/protofibrils to (a) elongate and (b)
      laterally associate. Our results demonstrate that (a) tails of K5 and K14 are
      required for filament stabilization; (b) the head of K5, but not of K14, is
      required for filament elongation and lateral alignments; and (c) the R/K L L E G
      E domains are required for lateral alignments, but not for filament elongation.

PMID- 1383233
TI  - Introns excised from the Delta primary transcript are localized near sites of
      Delta transcription.
AB  - Introns excised from the primary transcript of Delta (Dl), a Drosophila
      neurogenic gene, accumulate to unusually high levels in embryos. High resolution
      in situ hybridization reveals a striking localization of the excised introns to
      two foci per embryonic nucleus. The number of foci can be altered by varying the
      number of Dl genes present in the embryonic nucleus, suggesting that the excised
      introns are localized near sites of Dl transcription. This conclusion is
      supported by the observation that larval and imaginal disc nuclei containing two
      copies of Dl exhibit only one focus of intron accumulation, as expected for
      nuclei in which homologous chromosomes are paired. Interestingly, the excised
      introns do not appear to diffuse away from the foci until late prophase, at which
      time the foci disperse into numerous small dots of hybridization. These results
      suggest that the excised Dl introns may be associated with a structural element
      within the nucleus that is dissociated during cell division.

PMID- 1383234
TI  - Axonal transport of class II and III beta-tubulin: evidence that the slow
      component wave represents the movement of only a small fraction of the tubulin in
      mature motor axons.
AB  - Pulse-labeling studies demonstrate that tubulin synthesized in the neuron cell
      body (soma) moves somatofugally within the axon (at a rate of several millimeters
      per day) as a well-defined wave corresponding to the slow component of axonal
      transport. A major goal of the present study was to determine what proportion of
      the tubulin in mature motor axons is transported in this wave. Lumbar motor
      neurons in 9-wk-old rats were labeled by injecting [35S]methionine into the
      spinal cord 2 wk after motor axons were injured (axotomized) by crushing the
      sciatic nerve. Immunoprecipitation with mAbs which recognize either class II or
      III beta-tubulin were used to analyze the distributions of radioactivity in these
      isotypes in intact and axotomized motor fibers 5 d after labeling. We found that
      both isotypes were associated with the slow component wave, and that the leading
      edge of this wave was enriched in the class III isotype. Axotomy resulted in
      significant increases in the labeling and transport rates of both isotypes.
      Immunohistochemical examination of peripheral nerve fibers demonstrated that
      nearly all of the class II and III beta-tubulin in nerve fibers is located within
      axons. Although the amounts of radioactivity per millimeter of nerve in class II
      and III beta-tubulin were significantly greater in axotomized than in control
      nerves (with increases of +160% and +58%, respectively), immunoassay revealed no
      differences in the amounts of these isotypes in axotomized and control motor
      fibers. We consider several explanations for this paradox; these include the
      possibility that the total tubulin content is relatively insensitive to changes
      in the amount of tubulin transported in the slow component wave because this wave
      represents the movement of only a small fraction of the tubulin in these motor
      fibers.

PMID- 1383235
TI  - Myelin basic protein gene contains separate enhancers for oligodendrocyte and
      Schwann cell expression.
AB  - The DNA sequence between position +36 and -1907 of the murine myelin basic
      protein gene contains the enhancer and promoter elements necessary for abundant
      and cell specific expression in transgenic mice. Surprisingly, the pattern of
      expression promoted by this DNA fragment is a subset of that exhibited by the
      endogenous myelin basic protein (MBP) gene. Fusion genes prepared with this
      promoter/enhancer and a Lac Z reporter gene are expressed only in
      oligodendrocytes and not in Schwann cells, whereas the endogenous MBP gene is
      expressed in both cell types. The level of transgene expression measured by
      nuclear run-on experiments is very substantial and rivals that of the endogenous
      MBP gene. Furthermore, this 1.9-kb DNA fragment directs transcription on the same
      (or very similar) developmental schedule as the endogenous gene. These results
      indicate that the MBP promoter/enhancer sequences are at least tripartite: a core
      promoter, the oligodendrocyte enhancer elements, and a third component that
      either expands the specificity of the oligodendrocyte enhancer to include Schwann
      cells or acts independently to specifically stimulate transcription in Schwann
      cells.

PMID- 1383236
TI  - Intracellular localization of the P21rho proteins.
AB  - The three mammalian ras proteins associated specifically with the plasma membrane
      and this is essential for their biological activity. Two signals encoded within
      the extreme COOH terminus of the proteins specify this cellular localization; a
      CAAX box in combination with either a polybasic domain (p21K-rasB) or a
      palmitoylation site (p21Ha-ras and p21N-ras). All members of the ras-like and rho
      like subfamilies of the ras superfamily of small GTP-binding proteins also have
      CAAX boxes with potential second site sequences resembling either p21K-rasB or
      P21N-ras/Ha-ras. However it is not at all clear that they are each located at the
      plasma membrane, and in fact one of the ras-like proteins, rap1, has been
      localized to the Golgi (Beranger et al., 1991). None of the mammalian rho-like
      subfamily has yet been localized. Three forms (A, B, and C) of p21rho, the
      prototype of this family are known; the COOH termini of p21rhoA and p21rhoC
      resemble p21K-rasB with a polybasic domain, whereas p21rhoB resembles p21N-ras/Ha
      ras with two cysteine residues as potential palmitoylation sites. Despite this
      similarity to the p21ras proteins, rho proteins have been purified from both
      particulate and cytosolic fractions of a variety of tissues. In order to localize
      definitively the three rho proteins we have used an epitope tagging approach
      coupled to microinjection of living cells. We show that a small fraction of all
      three proteins is localized to the plasma membrane but the majority of p21rhoA
      and p21rhoC is cytosolic whereas p21rhoB is associated with early endosomes and a
      pre-lysosomal compartment. Along with the results obtained with chimeric
      molecules using heterologous proteins attached to rho COOH termini, this suggests
      that the p21rho proteins cycle on and off the plasma membrane and this may have
      important implications for their biological function.

PMID- 1383237
TI  - Hepatocyte growth factor is a potent angiogenic factor which stimulates
      endothelial cell motility and growth.
AB  - Hepatocyte Growth Factor (HGF, also known as Scatter Factor) is a powerful
      mitogen or motility factor in different cells, acting through the tyrosine kinase
      receptor encoded by the MET protooncogene. Endothelial cells express the MET gene
      and expose at the cell surface the mature protein (p190MET) made of a 50 kD
      (alpha) subunit disulfide linked to a 145-kD (beta) subunit. HGF binding to
      endothelial cells identifies two sites with different affinities. The higher
      affinity binding site (Kd = 0.35 nM) corresponds to the p190MET receptor. Sub
      nanomolar concentrations of HGF, but not of a recombinant inactive precursor,
      stimulate the receptor kinase activity, cell proliferation and motility. HGF
      induces repairs of a wound in endothelial cell monolayer. HGF stimulates the
      scatter of endothelial cells grown on three-dimensional collagen gels, inducing
      an elongated phenotype. In the rabbit cornea, highly purified HGF promotes
      neovascularization at sub-nanomolar concentrations. HGF lacks activities related
      to hemostasis-thrombosis, inflammation and endothelial cells accessory functions.
      These data show that HGF is an in vivo potent angiogenic factor and in vitro
      induces endothelial cells to proliferate and migrate.

PMID- 1383238
TI  - Hyaluronan-binding protein in endothelial cell morphogenesis.
AB  - Previous studies from several laboratories have provided evidence that
      interaction of hyaluronan (HA) with the surface of endothelial cells may be
      involved in endothelial cell behavior. We have recently characterized a mAb, mAb
      IVd4, that recognizes and neutralizes HA-binding protein (HABP) from a wide
      variety of cell types from several different species (Banerjee, S. D., and B. P.
      Toole. 1991. Dev. Biol. 146:186-197). In this study we have found that mAb IVd4
      inhibits migration of endothelial cells from a confluent monolayer after
      "wounding" of the monolayer. HA hexasaccharide, a fragment of HA with the same
      disaccharide composition as polymeric HA, also inhibits migration. In addition,
      both reagents inhibit morphogenesis of capillary-like tubules formed in gels
      consisting of type I collagen and basement membrane components. Immunocytology
      revealed that the antigen recognized by mAb IVd4 becomes localized to the cell
      membrane of migrating cells, including many of their lamellipodia. Treatment with
      high concentrations of HA hexamer causes loss of immunoreactivity from these
      structures. We conclude that HABP recognized by mAb IVd4 is involved in
      endothelial cell migration and tubule formation.

PMID- 1383239
TI  - Characterization of multiple adhesive and counteradhesive domains in the
      extracellular matrix protein cytotactin.
AB  - The extracellular matrix molecule cytotactin is a multidomain protein that plays
      a role in cell migration, proliferation, and differentiation during development.
      To analyze the structure-function relationships of the different domains of this
      glycoprotein, we have prepared a series of fusion constructs in bacterial
      expression vectors. Results obtained using a number of adhesion assays suggest
      that at least four independent cell binding regions are distributed among the
      various cytotactin domains. Two of these are adhesive; two others appear to be
      counteradhesive in that they inhibit cell attachment to otherwise favorable
      substrates. The adhesive regions were mapped to the fibronectin type III repeats
      II-VI and the fibrinogen domain. The morphology of the cells plated onto these
      adhesive fragments differed; the cells spread on the fibronectin type III repeats
      as they do on fibronectin, but remained round on the fibrinogen domain. The
      counteradhesive properties of the molecule were mapped to the EGF-like repeats
      and the last two fibronectin type III repeats, VII-VIII. The latter region also
      contained a cell attachment activity that was observed only after proteolysis of
      the cells. Several cell types were used in these analyses, including fibroblasts,
      neurons, and glia, all of which are known to bind to cytotactin. The different
      domains exert their effects in a concentration-dependent manner and can be
      inhibited by an excess of the soluble molecule, consistent with the hypothesis
      that the observed properties are mediated by specific receptors. Moreover, it
      appears that some of these receptors are restricted to particular cell types. For
      example, glial cells bound better than neurons to the fibrinogen domain and
      fibroblasts bound better than glia and neurons to the EGF fragment. These results
      provide a basis for understanding the multiple activities of cytotactin and a
      framework for isolating different receptors that mediate the various cellular
      responses to this molecule.

PMID- 1383242
TI  - The role of ion channels in insulin secretion.
AB  - Ion channels in beta cells regulate electrical and secretory activity in response
      to metabolic, pharmacologic, or neural signals by controlling the permeability to
      K+ and Ca2+. The ATP-sensitive K+ channels act as a switch that responds to fuel
      secretagogues or sulfonylureas to initiate depolarization. This depolarization
      opens voltage-dependent calcium channels (VDCC) to increase the amplitude of free
      cytosolic Ca2+ levels ([Ca2+]i), which triggers exocytosis. Acetyl choline and
      vasopressin (VP) both potentiate the acute effects of glucose on insulin
      secretion by generating inositol 1,4,5-trisphosphate to release intracellular
      Ca2+; VP also potentiates sustained insulin secretion by effects on
      depolarization. In contrast, inhibitors of insulin secretion decrease [Ca2+]i by
      either hyperpolarizing the beta cell or by receptor-mediated, G-protein-coupled
      effects to decrease VDCC activity. Repolarization is initiated by voltage- and
      Ca(2+)-activated K+ channels. A human insulinoma voltage-dependent K+ channel
      cDNA was recently cloned and two types of alpha 1 subunits of the VDCC have been
      identified in insulin-secreting cell lines. Determining how ion channels regulate
      insulin secretion in normal and diabetic beta cells should provide
      pathophysiologic insight into the beta cell signal transduction defect
      characteristic of non-insulin dependent diabetes (NIDDM).

PMID- 1383241
TI  - The dermal-epidermal junction of human skin contains a novel laminin variant.
AB  - We report the identification of a novel laminin variant that appears to be unique
      to a subset of epithelial basement membranes. The variant contains two chains
      electrophoretically and immunologically identical to the B1 and B2 chains.
      Epitopes contained in the laminin A chain are absent from the molecule, and a 190
      kD chain substitutes for the A chain. V8 protease analysis and Western blotting
      studies indicate that the variant 190-kD chain shows structural and immunological
      similarity to the 200-kD chain of kalinin. Rotary shadowing analysis indicates
      that the 190-kD chain contributes a large globular structure to the variant long
      arm, but lacks the short arm contributed to laminin by the A chain. The variant
      is produced by cultured skin explants, human keratinocytes and a squamous cell
      carcinoma line, and is present in human amniotic fluid. Polyclonal antibodies
      raised to kalinin, a recently characterized novel component of anchoring
      filaments, and mAb BM165 which recognizes a subunit of kalinin (Rousselle et al.,
      1991) cross react with the variant under nonreducing conditions.
      Immunohistological surveys of human tissues using the crossreacting antikalinin
      antiserum indicate that the distribution of this laminin variant is at least
      restricted to anchoring filament containing basement membranes. We propose the
      name K-laminin for this variant.

PMID- 1383243
TI  - Immunological evidence that plants use both HDEL and KDEL for targeting proteins
      to the endoplasmic reticulum.
AB  - The epitopes of two monoclonal antibodies raised to a putative auxin receptor
      have been mapped. Carboxy-peptidase A digestion of the antigen, auxin-binding
      protein (ABP) purified from maize, completely abolished binding of antibody MAC
      256 and impaired binding of MAC 259, suggesting that they both recognise C
      terminal epitopes. Published sequences of ABP showed that the C terminus was
      KDEL, a tetrapeptide used for targeting proteins to the ER in animal cells. We
      have used this short homology to confirm that the two monoclonals recognise C
      terminal KDEL, showing that animal KDEL proteins and synthetic KDEL peptides are
      recognised and that animal cell ER is stained strongly and specifically. Sucrose
      density gradient fractionation of maize microsomal membranes showed that plant
      KDEL proteins, including ABP, fractionated with markers for the endoplasmic
      reticulum. However, few proteins are stained by anti-KDEL monoclonals in plants.
      For comparison, a monoclonal antibody raised to a synthetic HDEL peptide was also
      used and found to stain a set of proteins in all plant species tested. The anti
      HDEL and anti-KDEL monoclonals were sequence specific, staining different
      proteins. On density gradient fractionation HDEL proteins also banded with ER
      marker activities. However, the intracellular distribution of HDEL and KDEL
      proteins determined by immunofluorescence was different. Whereas HDEL proteins
      showed a distribution characteristic of plant ER, and this localisation was
      confirmed by immunogold labelling of ultrathin sections and electron microscopy,
      KDEL proteins showed strong fluorescence in discrete parts of the cell cortex.
      These observations are discussed in terms of the potential these monoclonal
      antibodies have as markers for ER and of the role ABP plays in plant cell
      signalling.

PMID- 1383240
TI  - A truncated laminin chain homologous to the B2 chain: structure, spatial
      expression, and chromosomal assignment.
AB  - We describe the identification of a novel laminin chain. Overlapping clones were
      isolated from a human fibrosarcoma HT1080 cell cDNA library spanning a total of
      5,200 bp. A second set of clones contained an alternative 3' end sequence giving
      a total of 4,316 bp. The longer sequence contained an open reading frame for a
      1,193-residue-long polypeptide. The alternative sequence was shortened at the
      carboxyl-terminal end coding for a 1,111-residue-long polypeptide. The amino acid
      sequence contained 21 amino acids of a putative signal peptide and 1,172 residues
      or alternatively 1,090 residues of a sequence with five distinct domains
      homologous to domains I-V in laminin chains. Comparison of the amino acid
      sequences showed that the novel laminin chain is homologous to the laminin B2
      chain. However, the structure of the novel laminin chain isolated here differs
      significantly from that of the B2 chain in that it has no domain VI and domains
      V, IV, and III are shorter, resulting in a truncated laminin chain. The
      alternative sequence had a shortened domain I/II. In accordance with the current
      nomenclature, the chain characterized here is termed B2t. Calculation of possible
      chain interactions of laminin chains with the B2t chain domain I/II indicated
      that the B2t chain can replace the B2 chain in some laminin molecules. The gene
      for the laminin B2t chain (LAMB2T) was localized to chromosome 1q25-q31 in close
      proximity to the laminin B2 chain gene. Northern analysis showed that the B2t
      chain is expressed in several human fetal tissues but differently from the
      laminin B1 and B2 chains. By in situ hybridization expression of the B2t chain
      was localized to specific epithelial cells in skin, lung, and kidney as opposed
      to a general epithelial and endothelial cell expression of the laminin B2 chain
      in the same tissues.

PMID- 1383244
TI  - Mitochondrial gene expression in the human gastrointestinal tract.
AB  - In the human gastrointestinal epithelium, in situ hybridisation demonstrates that
      12 S and 16 S mitochondrial ribosomal RNAs show maximal steady-state levels on
      the surface epithelial cells of the normal small intestine and colon. The
      mitochondrial mRNAs, cytochrome b and NADH dehydrogenase (IV) have a uniform
      distribution throughout the crypt and surface (villus) epithelial cells of the
      small intestine and colon. Histochemical stains for the activity of the
      mitochondrial respiratory chain enzymes succinate dehydrogenase and cytochrome
      oxidase also show almost uniform activities throughout the crypt-surface
      epithelial cell axis in the small and large intestines. In sections of normal
      human oesophagus the levels of mitochondrial ribosomal RNAs, mitochondrial mRNAs
      and the activities of mitochondrial respiratory chain enzymes are maximal over
      the basal cells of the stratified squamous epithelium. These results show a
      relative increase in mitochondrial ribosomal RNA expression compared with
      mitochondrial mRNAs in surface cells of simple intestinal epithelia.

PMID- 1383246
TI  - Children's experience of surgery: creating a holistic environment.

PMID- 1383245
TI  - Cytokeratins and retinal epithelial cell behaviour.
AB  - The expression of cytokeratins 18 and 19 by human retinal pigment epithelial
      cells (HRPE) has been suspected of being associated with HRPE proliferation. We
      have investigated the involvement of these cytokeratin subtypes in the
      proliferative and migratory behaviour of cultured HRPE. Cell proliferation
      markers (bromodeoxyuridine and proliferating cell nuclear antigen) and the
      cytokeratins were identified using immunohistochemical techniques. In vitro,
      cytokeratins 18 and 19, as detected by the monoclonal antibodies RGE 53 and
      K4.62, were expressed in a subset of HRPE and this subset was significantly less
      likely to be proliferating. Micro-chemotaxis chambers were used to study
      migrating cells and immunohistochemical staining for cytokeratins 18 and 19
      revealed that actively migrating cells always expressed these two cytokeratins,
      whereas stationary cells did not label for these cytokeratin subtypes. It was
      apparent that cytokeratins 18 and 19 were not markers of proliferation, but were
      involved in the mobility of HRPE in vitro. Cytokeratins 18 and 19 may be useful
      indicators of simple epithelial cell migration in tissues.

PMID- 1383247
TI  - Ion channels in action potential generation.
AB  - Molecular structure-function studies have identified the two key regions--the
      voltage sensor and pore--of the sodium and potassium channels responsible for the
      action potential in nerve axon. Mutational analysis has focused on the amino
      acids that are most important in each region. Similar studies in myocytes and
      nerve cell bodies are now being pursued.

PMID- 1383248
TI  - Treatment options in benign prostatic hypertrophy.
AB  - Surgery remains the first choice in patients with progressive urinary symptoms.
      Medical therapy--with antiandrogens, 5 alpha-reductase inhibitors, or alpha
      adrenergic antagonists--may be useful in selected cases.

PMID- 1383249
TI  - High-performance liquid chromatographic procedure for the determination of a non
      nucleoside HIV-1 reverse transcriptase inhibitor in human plasma.
AB  - A method for the determination of a non-nucleoside HIV-1 reverse transcriptase
      inhibitor in human plasma is described. Plasma samples are extracted using phenyl
      solid-phase extraction columns. The extract is analyzed by high-performance
      liquid chromatography with a polybutadiene-coated alumina column and a mobile
      phase of methanol-0.025 M pH 8 dibasic sodium phosphate buffer (1:1, v/v).
      Detection is based on ultraviolet absorbance at 326 nm. The assay was validated
      in the concentration range 10-500 ng/ml when 1-ml aliquots of plasma are
      extracted. The assay has been utilized to support human pharmacokinetic studies.

PMID- 1383250
TI  - Measurement of beta-endorphin in human plasma by high-performance liquid
      chromatography with electrochemical detection: validation of a method employing
      the simultaneous purification and concentration of beta-endorphin.
AB  - The simultaneous purification and concentration of synthetic human beta-endorphin
      from plasma is described, which when used together with an appropriate isocratic
      high-performance liquid chromatographic-electrochemical detection (HPLC-ED)
      system allows the determination of elevated physiological levels of beta
      endorphin. Purification of plasma was gained by flash-freezing in liquid
      nitrogen, acidifying with 100 microliters of trifluoroacetic acid (10%, v/v) per
      ml of plasma, thawing at 4 degrees C and centrifuging to remove any precipitate.
      Solid-phase extraction with silica sorbent was utilised, which allowed further
      isolation of the analyte, a method of concentration and a procedure whereby beta
      endorphin could be transferred to the HPLC mobile phase. Silica sorbent
      demonstrated greater selectivity than C18 for synthetic human beta-endorphin and,
      in addition, provided improved recovery of this analyte when utilising elution
      volumes of 500 microliters or less. Proteolytic degradation and heparin-induced
      high-affinity binding in plasma were shown not to effect the recovery of beta
      endorphin if blood was rapidly chilled and plasma quickly obtained, frozen and
      acidified. Validation of this purification/concentration method using [125I]beta
      endorphin demonstrated a recovery of 85.6% which was not jeopardised when
      concentrating the sample twenty-fold. This provided an increase in the
      sensitivity of detection, when used in conjunction with HPLC-ED, from 5 ng/ml to
      250 pg/ml.

PMID- 1383251
TI  - Construction and use of two alpha-human atrial natriuretic peptide-fragment
      affinity chromatography columns in the isolation of C- and N-terminal epitope
      specific antibodies for use in a prototype alpha-hANP biosensor.
AB  - Two alpha-human atrial natriuretic peptide (alpha-hANP) based affinity
      chromatography columns were produced by covalently immobilizing the C- and N
      terminal epitopes of alpha-hANP. The stationary phase was made from a controlled
      pore-glass bead solid support, which was silanized and treated with
      sulphosuccinimidyl 4-(maleimidomethyl)cyclohexyl carboxylate before the
      individual fragments were immobilized by substitution at their thiol groups.
      These columns were used to isolate alpha-hANP-specific antibodies from a goat
      anti-alpha-hANP serum, which were then further sorted according to their epitope
      specifity. These C- and N-terminal epitope-specific antibodies were in turn used
      as components in the construction of an alpha-hANP biosensor based on an enzyme
      linked immunosorbent assay (ELISA) sandwich principle. Initial in vitro testing
      of the sensor using a physiological alpha-hANP solution showed a reproducible
      response to the peptide. There is to date no other equally fast, sensitive and
      precise method available to detect this peptide. This alpha-hANP sensor may prove
      to be an invaluable aid in human medicine as a monitor of patient status during
      transplant surgery, for example, an area inaccessible to radioimmunoassay and
      normal ELISA techniques.

PMID- 1383252
TI  - Simultaneous solid-phase extraction and chromatographic analysis of morphine and
      hydromorphone in plasma by high-performance liquid chromatography with
      electrochemical detection.
AB  - High-performance liquid chromatography has become an important analytical tool
      for the quantitation of opioid drugs. Using solid-phase extraction and
      coulometric electrochemical detection, we have developed a chromatographic method
      for the simultaneous measurement of morphine and hydromorphone which is both
      sensitive and specific. Using 1 ml of plasma, intra-assay and inter-assay data
      show that the detection limit for accurate quantitation of these compounds is
      about 1.2 ng/ml (coefficient of variation 11.6%) for morphine and 2.5 ng/ml
      (coefficient of variation 10.5%) for hydromorphone. The method is simple and
      readily adaptable to most pharmacokinetic studies and toxic screens involving
      these drugs.

PMID- 1383253
TI  - Gas chromatographic-mass spectrometric method for analysis of a pyrimido-s
      triazine and some of its metabolites in dog urine.
AB  - 3-Phenylpyrimido-[3,4-a]-s-triazines exhibit antiparasitic, antibacterial and
      antifungal activity. In order to study the metabolism of these heterocycles, 9,9
      diethyl-3-phenyl-6,8-dioxo-2,3,4,5,6,7,8,9-octahydropyrimido[3 ,4-a]-s- triazine
      (TZ) was administered to dogs. Three potential metabolites were synthesized, and
      these models were identified and quantified with gas chromatography-mass
      spectrometry. The heterobicyclic compounds, TZ and its hydroxy derivative,
      underwent thermal degradation under chromatographic conditions. Dog urine spiked
      with the model metabolites was extracted, and the substances were quantified. The
      urine of dogs treated with TZ was studied, and two of the potential metabolites
      were recovered, identified and quantified.

PMID- 1383255
TI  - Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein
      3 protease found in seminal plasma.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3), the major serum carrier
      protein for the IGFs, is absent from Western ligand blots of seminal plasma, but
      is detectable by RIA. IGFBP-3 protease activity has recently been described in
      pregnancy serum. We investigated the possibility that seminal plasma contains an
      IGFBP-3 protease, by incubating seminal plasma with 125I-labeled human IGFBP-3.
      Seminal plasma was found to have potent IGFBP-3 protease activity with a cleavage
      pattern different from that of pregnancy serum. Prostate-specific antigen (PSA)
      is a serine protease found in semen. Autoradiographs measuring IGFBP-3 protease
      activity demonstrated that purified PSA cleaved IGFBP-3, yielding a cleavage
      pattern identical to that of seminal plasma. IGFBP-2 and -4 in seminal plasma
      were not degraded by PSA. Cleavage of IGFBP-3 by PSA resulted in a marked
      reduction in the binding affinity of the fragments to IGF-I, but not IGF-II. We
      speculate that PSA may serve to modulate IGF function within the reproductive
      system or in prostate cancer by altering IGF-IGFBP-3 interactions.

PMID- 1383254
TI  - Insulin-like growth factor binding proteins in ovarian follicles from women with
      polycystic ovarian disease: cellular source and levels in follicular fluid.
AB  - The follicular fluid (FF) of human ovaries contains insulin-like growth factor
      binding proteins (IGFBPs) which may regulate the bioavailability of the IGFs.
      Previously we showed discrete changes in IGFBP concentrations in FF which
      correlated with the physiological state of the follicle. The purpose of the
      present study was to test the hypothesis that IGFBPs in FF may be increased in
      polycystic ovarian disease (PCO). FF was aspirated from PCO follicles and size
      matched healthy and atretic follicles from normal ovaries of naturally cycling
      women. The IGFBPs in FF samples were studied by ligand blot analysis with 125I
      IGF-II and by immunoblot analysis using specific antisera to five human IGFBPs.
      Of six IGFBP bands in PCO FF, three were identified as IGFBP-2, IGFBP-3, and
      IGFBP-4. Bands (29K and 31K) were not identified by any of the five IGFBP
      antisera. The total IGF binding capacity was increased in PCO FF relative to
      normal healthy or atretic FF. IGFBP-3 was the predominant BP present in FF from
      PCO follicles as well as normal healthy and atretic follicles with no significant
      difference in any of the groups of follicles studied. IGFBP-2, IGFBP-4, and the
      29K BP were present in smaller amounts, but there were significantly higher
      levels of each of these BPs in PCO follicles than in normal healthy follicles.
      Only IGFBP-4 was elevated in PCO follicles relative to normal atretic follicles
      indicating that the pattern of IGFBP expression in PCO FF was very similar to the
      pattern observed in atretic follicles. To determine the source of the IGFBPs in
      FF, granulosa or theca cells were cultured (up to 6 days) in serum-free medium.
      Ligand blot analysis of the conditioned medium revealed basal secretion of IGFBP
      3 by both theca and granulosa cells. FSH inhibited granulosa cell IGFBP-3
      production but increased the 29K BP in the medium. Transforming growth factor
      beta stimulated basal IGFBP-3 secretion and reversed the FSH effects. Human CG
      (100 ng/mL) inhibited theca cell IGFBP-3 production but did not stimulate any
      other IGFBP. The results of our studies indicate that IGFBP-2, IGFBP-4, and the
      29K BP are significantly increased in PCO FF and that gonadotropins and TGF-beta
      regulate the production of IGFBPs by human theca and granulosa cells.

PMID- 1383256
TI  - Expression of messenger ribonucleic acids encoding neuropeptide-Y, substance-P,
      and vasoactive intestinal polypeptide in human pituitary.
AB  - The local production of autocrine or paracrine agents in endocrine tissues
      represents an important level of hormonal regulation. The synthesis of
      neuropeptide-Y (NPY), substance-P (SP), and vasoactive intestinal peptide (VIP)
      in the rat anterior pituitary gland has been well demonstrated. We have now
      studied their expression in human postmortem pituitary tissue. Northern blot
      analysis of poly(A)+ RNA from whole human pituitaries revealed mRNA encoding the
      precursors for NPY, SP, and VIP whose hybridization characteristics were
      indistinguishable from those of the same mRNAs described in previously
      characterized human tissues. VIP mRNA was detectable in all samples tested, with
      NPY and preprotachykinin-A mRNA (which encodes SP) detectable in a subset of the
      pituitaries. The concentration of immunoreactive NPY in whole human pituitary was
      3.8 +/- 1.1 pmol/g wet wt in males and 2.9 +/- 0.5 pmol/g wet wt in females (mean
      +/- SEM; n = 10), that of SP was 3.1 +/- 0.4 pmol/g wet wt in males and 5.2 +/-
      1.3 pmol/g wet wt in females (n = 10), and that of VIP was 8.1 +/- 2.9 pmol/g wet
      wt in males and 5.3 +/- 1.6 pmol/g wet wt in females (n = 10). Size-fractionation
      of pituitary extracts by gel permeation chromatography revealed single peaks of
      NPY and VIP-like immunoreactivity in the positions of the standards, while SP
      like immunoreactivity mostly eluted in the position of synthetic SP, with two
      minor immunoreactive peaks eluting earlier. The low levels of NPY, SP, and VIP
      and their mRNAs in the human pituitary are consistent with peptides having an
      autocrine/paracrine, rather than endocrine, mode of action.

PMID- 1383257
TI  - Immune response to GOR, a marker for non-A, non-B hepatitis and its correlation
      with hepatitis C virus infection.
AB  - Recently, identification and molecular cloning of a host cellular gene designated
      GOR from chimpanzees experimentally infected with non-A, non-B hepatitis (NANBH)
      agent was reported. It was further demonstrated that there is a close association
      between the immune response to an antigenic peptide of GOR (GOR2) and NANBH. In
      order to define the specificity of the immune response, in the present study we
      have identified an additional epitope in the GOR gene sequence, upstream from
      GOR2, and studied its correlation with the immune response to hepatitis C virus
      (HCV) in NANBH patients. An enzyme-linked immunoassay (EIA) was developed which
      utilizes synthetic peptides designated spGOR346 and spGOR2 as the serological
      target for the detection of anti-GOR antibodies in patient serum samples from
      various hepatic and non-hepatic disease categories. GOR peptides identified 80
      90% of the NANBH samples that were positive for HCV C100-3 and about 70% of the
      NANBH samples that were positive by Abbott prototype second-generation HCV
      antibody assay. Among a normal donor population(s), only 2-3% of the samples were
      positive for antibodies to GOR sequences, whereas from the patient categories
      unrelated to viral hepatitis as well as various nonhepatic diseases, the immune
      response to both GOR peptides was closely associated with the presence of
      antibodies to HCV. The data indicate that antibodies to GOR is a marker
      associated with NANBH.

PMID- 1383258
TI  - Quantitation of antigen-specific immune responses in human immunodeficiency virus
      (HIV)-infected individuals by limiting dilution analysis.
AB  - The lymphocyte proliferative response to recall antigens is lost following HIV
      infection. We sought to devise a means by which the functional immune status of
      persons in the early stages of HIV infection could be monitored quantitatively.
      The response to tetanus toxoid was examined in 45 HIV-infected individuals and 11
      controls using conventional lymphocyte proliferative assays concurrently with
      limiting dilution analysis utilizing the secretion of interleukin-2 as the
      measure of a response. Our data show that the limiting dilution analysis detects
      tetanus toxoid-reactive T cells in 80% of those tested, as compared to only 44%
      by proliferation. However, the frequency of tetanus-reactive T cells in HIV
      infected individuals (median frequency = 1/59,156) is decreased five-fold as
      compared to seronegative controls (median frequency = 1/11,599). Longitudinal
      studies demonstrated a time-dependent decrease in the frequency of tetanus
      specific T cell responses in the HIV-infected individuals. Thus, the limiting
      dilution analysis is a quantitative approach for detecting antigen-specific T
      cells in HIV-infected individuals, and may be used to monitor changes in T cell
      function in HIV infection.

PMID- 1383260
TI  - Oestradiol enhances in vitro the histamine release induced by embryonic histamine
      releasing factor (EHRF) from uterine mast cells.
AB  - The relationship between maternal hormones and factors secreted by the implanting
      embryo is still controversial. We have analysed the in-vitro effect of oestradiol
      and human embryo-derived histamine-releasing factor (EHRF) on histamine release
      from rat uterine mast cells. Rat uterine mast cells which were preincubated with
      oestradiol and then challenged with human EHRF gave histamine release values two-
      to threefold higher than those without preincubation. The enhancement observed
      was time- and temperature-dependent. A similar enhancement was obtained with
      human sensitized basophils but not with rat peritoneal mast cells. Oestradiol,
      used as a direct challenge, did not induce any histamine release from either rat
      uterine or peritoneal mast cells, or from human sensitized basophils. Oestradiol
      preincubation also enhanced the histamine release induced by anti-IgE but did not
      enhance the histamine release induced by substance P or compound 48/80, two
      secretagogues that are not mediated by IgE. Moreover, uterine fragments derived
      from rats at various oestrus phases, with different amounts of endogenous
      oestrogen, were challenged in vitro with EHRF. The release of histamine by mast
      cells was higher at the proestrus and preimplantation phases than at dioestrus.
      All these findings suggest that the interaction of oestradiol with rat uterine
      mast cells was capable of enhancing in vitro the histamine releasing effect of
      EHRF.

PMID- 1383259
TI  - Baboon T cell lymphomas expressing the B cell-associated surface proteins CD40
      and Bgp95.
AB  - Papio hamadryas baboons in the Sukhumi colony develop enzootic outbreaks of
      malignant lymphomas with an incidence of about 1.5% per year among adults of the
      high-risk stock. We investigated the surface phenotypes of cells from normal and
      lymphomatous animals using antibodies against human lymphocyte antigens. We found
      that more than 80% of the lymphomas that developed during the last 3 years were
      characterized histologically to be of the peripheral T cell type. Generally, the
      lymphomatous cells also expressed high levels of MHC class II DR protein, CD18
      (LFA-1 beta chain), and CD45RO. Surprisingly, these cells also expressed on their
      surface two proteins previously characterized as being relatively B cell
      restricted: CD40 and Bgp95. These proteins were never found on the peripheral
      blood T cells from normal animals. The expression of these two gene products was
      confirmed by RNA blotting and immunoprecipitation. In most cases, the two B cell
      associated proteins were expressed on the predominant T cell subsets; we found
      both B cell proteins on CD4+, CD8+ as well as on the CD4/8 double-positive cells
      when these subsets were expressed at high levels. About 90% of these animals are
      seropositive for Herpesvirus papio and human T cell leukemia virus-1 (HTLV-1)
      before developing outright lymphomas. In all of the lymphoma samples, HTLV-1 tax
      DNA sequences were detected by PCR amplification. Whether or not HTLV-1 or the
      Herpesvirus papio gene products influence the surface expression of CD40 and
      Bgp95 remains to be determined.

PMID- 1383261
TI  - Endothelial cell migratory signal produced by human endometrium during the
      menstrual cycle.
AB  - Human endometrial explants were cultured in a three-dimensional collagen/bovine
      aortic endothelial cell (BAEC) matrix to measure angiogenic activity, as
      represented by migration of BAEC towards the explants. The 57 endometrial
      biopsies were classified by histological appearance into nine stages of the
      menstrual cycle; five proliferative groupings, three secretory groupings and one
      menstrual. The BAEC migratory score was taken as the average for 12 explants
      assayed from each biopsy. The results showed two significant peaks of BAEC
      migratory activity, one during the early proliferative phase and one during the
      mid--late proliferative phase. There was a significant drop in the BAEC migratory
      signal from early--mid-proliferative endometrial explants compared to most other
      stages of the cycle. The results also show a non-significant rise in BAEC
      migratory activity in the mid-secretory phase of the cycle. Overall, the results
      support the concept of two or three different endometrial angiogenic events
      during the human menstrual cycle, a post-menstrual repair, a mid--late
      proliferative growth and a lesser mid-secretory activity that may be associated
      with spiral arteriole growth. Each of these events occurs under different
      hormonal environments and will need to be investigated separately in terms of
      local mechanisms controlling angiogenesis.

PMID- 1383262
TI  - Insulin-like growth factor-I stimulates amino acid accumulation in cultured human
      granulosa cells.
AB  - In order to study the effect of insulin-like growth factor (IGF)-I on amino acid
      transport, granulosa-luteal cells were obtained from stimulated cycles in women
      undergoing in-vitro fertilization. The cells were precultured for 1-3 days in
      serum-containing medium. The medium was then changed to serum-free with added IGF
      I and/or human chorionic gonadotrophin (HCG). Following 24 h culture, the
      cellular uptake of [14C]alpha-aminoisobutyric acid AIB (0.1 mM, 0.6 mCi/ml) was
      studied during a 2-6 h incubation. The results showed that IGF-I (10-100 ng/ml)
      consistently stimulated AIB uptake to levels which were 44 +/- 7% above the
      control (n = 11 experiments). The stimulatory effect of IGF-I was abolished by
      HCG and was reduced by IGF-binding protein. In conjunction with previous findings
      that IGF-I stimulates the uptake and incorporation of thymidine into DNA, these
      results suggest that IGF-I is involved in growth of human granulosa-luteal cells.

PMID- 1383263
TI  - The influence of ovarian response on gamete intra-Fallopian transfer outcome in
      older women.
AB  - Fecundity declines with increasing age in women. The pregnancy rate is lower in
      in-vitro fertilization/embryo transfer (IVF/ET) in women aged greater than or
      equal to 40 years. We analysed 349 consecutive gamete intra-Fallopian transfer
      (GIFT) cycles in women aged greater than or equal to 40 years to identify factors
      which affected the outcome. A maximum of four oocytes were transferred in GIFT as
      recommended by the Interim Licensing Authority; 61 women (17.5%) had a positive
      serum beta-human chorionic gonadotrophin, 35 (10%) had a miscarriage and 26
      (7.5%) delivered live infants. The pregnancy rate was lower than with younger
      women while the conception loss was higher. Pregnancy and delivery rates
      increased as the number of oocytes retrieved increased but declined again if
      greater than 10 oocytes were retrieved. If 1-3 oocytes were retrieved, the
      pregnancy rate was 9.7% and the delivery rate was 3.9%; if 4-10 oocytes were
      retrieved, the pregnancy rate was 22.1% and the delivery rate was 10.1%, and when
      greater than 10 oocytes were retrieved, the rates were 17.6 and 5.9%
      respectively. The highest pregnancy rate was when four oocytes were transformed
      in GIFT (22.4%) and the delivery rate was 10.0%. An adequate response to long
      down-regulation with gonadotrophin-releasing hormone agonist was also a factor
      associated with high delivery rates (13.5%). We conclude that the delivery rate
      after GIFT in women aged greater than or equal to 40 years is low, but there is a
      subgroup who have an acceptable delivery rate because of a good ovarian response.
      In this group, pituitary down-regulation improves the outcome of treatment.

PMID- 1383264
TI  - Analysis of serum human chorionic gonadotrophin levels in normal singleton,
      multiple and abnormal pregnancies.
AB  - Some researchers claim that first trimester beta-human chorionic gonadotrophin
      (beta HCG) levels have a constant doubling time; others suggest doubling time
      increases as pregnancy progresses. This study was designed to settle the debate
      by analysing a large series of serial serum beta HCG determinations from 143
      pregnant women whose day of ovulation was precisely determined. Regression
      analysis was used to evaluate linear and quadratic models for the relationship of
      HCG with time in normal pregnancies. Doubling times were calculated for three
      time periods: 10-20 days post-ovulation (period 1); 21-30 days post-ovulation
      (period 2); greater than 30 days post-ovulation (period 3). Analysis of variance
      was used to compare the mean doubling time by time period and type of pregnancy
      (single, multiple, spontaneous abortion and ectopic). The analysis showed that a
      quadratic model best described the pattern of HCG rise in early normal pregnancy.
      Furthermore, for normal pregnancies, the mean doubling time increased
      significantly with advancing gestational age between time periods 1 and 2 and
      between periods 2 and 3. The mean doubling time was the same for single and
      multiple pregnancies. The doubling time was prolonged with ectopic pregnancy in
      period 1; and for aborters reaching ultrasound at 8 weeks, the doubling time was
      normal in period 1 but prolonged in period 2. Careful observation of the doubling
      time may aid clinicians in the detection of abnormal pregnancies.

PMID- 1383265
TI  - Detection of Norwalk virus in stool by polymerase chain reaction.
AB  - A method of reverse transcription (RT) and polymerase chain reaction (PCR) for
      the detection of Norwalk virus in human stools was developed. A cationic
      detergent, cetyltrimethylammonium bromide, was found to effectively remove from
      stool extracts factors that inhibit the RT-PCR assay. The specificities of the
      tests were shown by hybridization of the amplified DNA with Norwalk virus
      specific cDNA probes and a consistent correlation between virus detection in
      stools and infection of volunteers. RT-PCR detected virus in stool samples
      diluted 10(-4) and was about 100 times more sensitive than dot blot
      hybridization. In serial stool samples collected before and at different times
      after inoculation of 10 volunteers with Norwalk virus, 37 of 55 were positive by
      RT-PCR, but only 27 were positive by dot blot hybridization (chi 2 = 22.96; P
      less than 0.001). Further application of this method should allow detection of
      Norwalk virus in food or environmental samples such as shellfish and shellfish
      waters.

PMID- 1383266
TI  - Ribotyping of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex.
AB  - The Acinetobacter calcoaceticus-Acinetobacter baumannii complex consists of four
      genotypically distinct but phenotypically very similar bacterial species or DNA
      groups: A. calcoaceticus (DNA group 1), A. baumannii (DNA group 2), unnamed DNA
      group 3 (P. J. M. Bouvet and P. A. D. Grimont, Int. J. Syst. Bacteriol. 36:228
      240, 1986), and unnamed DNA group 13 (I. Tjernberg and J. Ursing, APMIS 97:595
      605, 1989). Because strains in this complex cause nosocomial outbreaks, it is
      important to be able to identify them as completely as possible. Ribotyping could
      provide such identification. Therefore, ribotyping was done on 70 strains in the
      A. calcoaceticus-A. baumannii complex with known DNA group affiliations by use of
      restriction enzymes EcoRI, ClaI, and SalI. A nonradioactive digoxigenin-11-dUTP
      labeled Escherichia coli rRNA-derived probe was used. With any of the three
      restriction enzymes, banding patterns that were specific for each DNA group were
      seen. All 70 strains showed banding patterns that could identify them to the
      correct DNA group by use of any two of the three enzymes. In addition, banding
      patterns that could separate strains within any one DNA group were present. The
      discriminatory index of P. Hunter and M. Gaston (J. Clin. Microbiol. 26:2465
      2466, 1988), applied to all strains with the combined results obtained with all
      three enzymes, revealed a value of 0.99. For strains in each DNA group, the value
      varied from 0.93 to 0.98. These results indicate the high discriminatory power of
      the system when used for epidemiological typing.

PMID- 1383267
TI  - Development of cDNA probes for typing group A bovine rotaviruses on the basis of
      VP4 specificity.
AB  - Dot and Northern (RNA) blot hybridization assays were developed for the P typing
      of group A bovine rotaviruses (BRV) by using cDNA probes prepared from gene
      segment 4. The probes were prepared by polymerase chain reaction amplification of
      hyperdivergent regions (nucleotides 211 to 686) of BRV strain UK, IND, NCDV, and
      Cr VP4 cDNA by using specific oligonucleotide primers. The probes were P type
      specific (VP4) and exhibited little or no cross-reactivity with double-stranded
      RNA from heterologous rotavirus P types. Our studies indicate that at least three
      P types, as defined by polymerase chain reaction-derived VP4 gene probes from the
      UK, NCDV, and Cr strains, exist among the seven BRV isolates tested.

PMID- 1383268
TI  - Reverse transcription and polymerase chain reaction amplification of rRNA for
      detection of Helicobacter species.
AB  - Sequence data on Helicobacter pylori 16S rRNA were used to select two 22-base
      oligonucleotide primers for use in a polymerase chain reaction (PCR) for
      detection of H. pylori. H. pylori cells were treated with lysis buffer, boiled,
      and chloroform extracted. Reverse transcription of rRNA was followed by PCR
      amplification (RT-PCR) of the synthesized cDNA and 16S rRNA gene. The amplified
      PCR products were analyzed by agarose gel electrophoresis and Southern blotting.
      Using ethidium bromide-stained agarose gels, we were able to detect the expected
      500-bp DNA fragment from as few as two H. pylori organisms per reaction. The
      specificity of the RT-PCR assay was tested with 27 clinical isolates and related
      reference strains; although the number of bacterial cells used per reaction was
      10(5)-fold greater than the number of H. pylori organisms used, amplification was
      detected only with bacteria in the same genus, H. cinaedi and H. mustelae. Ten H.
      pylori organisms per biopsy specimen were detected on agarose gels when organisms
      were added to samples prepared from a processed colon biopsy sample. RT-PCR
      results were consistent with urea breath test and culture results in 14 of 15
      gastric biopsy specimens; the specificity was 100%. RT-PCR of rRNA from H. pylori
      increased the sensitivity of pathogen detection at least 25- to 50-fold compared
      with that of previous PCR assays. This low level of detection by RT-PCR assay may
      prove to be well suited for verifying eradication following therapy.

PMID- 1383269
TI  - Cellular and humoral immune responses to rubella virus structural proteins E1,
      E2, and C.
AB  - Better understanding of cell-mediated immune responses to rubella virus would
      provide the basis for the development of safe and effective vaccines against
      rubella and would aid in analysis of the pathophysiology of congenital rubella
      syndrome. We have expressed individual rubella virus structural proteins, E1, E2
      and C, via vaccinia virus recombinants. Using the expressed recombinant proteins
      as antigens, we were able to demonstrate antigen-specific lymphocyte
      proliferative responses in control individuals and individuals with congenital
      rubella syndrome. Among the two human groups studied, E1 glycoprotein proved to
      be a better immunogen than E2 or C. For the control individuals, significant
      differences in proliferative responses to the structural proteins E1, E2, and C
      were observed. These differences were not significant in individuals with
      congenital rubella syndrome. In parallel to the lymphoproliferative responses,
      immunoglobulin G responses were also found directed mainly to the E1
      glycoprotein. These results suggest that E1 may be the most important rubella
      virus antigen to study in determining the domains required for constructing
      subunit vaccines against rubella.

PMID- 1383270
TI  - Serological studies of antigenic similarity between Japanese spotted fever
      rickettsiae and Weil-Felix test antigens.
AB  - Acute and convalescent-phase sera obtained from 10 patients infected with a
      Japanese strain of spotted fever group (SFG) rickettsia were tested by the
      indirect immunoperoxidase test, the Weil-Felix test, an enzyme-linked
      immunosorbent assay (ELISA), and immunoblotting. By the Weil-Felix test, the
      reactivity of these sera to the OX2 antigen was higher than those to the OX19
      antigen, as is the case with sera from persons infected with other SFG
      rickettsiae. By ELISA, the titers of immunoglobulin M (IgM) antibodies against
      OX2 corresponded to the Weil-Felix test titers of these sera against OX2 but not
      to the titers obtained with IgG antibodies. The reactivity of the patient sera
      with the OX2 antigen in the Weil-Felix test was probably due to IgM antibodies
      against antigens which OX2 and SFG rickettsiae have in common. By immunoblotting
      tests, both IgG and IgM antibodies from the patient sera reacted with
      lipopolysaccharides from SFG rickettsiae and Proteus strain OX2. These results
      may show that these lipopolysaccharides contain similar epitopes.

PMID- 1383271
TI  - Mechanisms underlying abnormal trafficking of malignant progenitors in chronic
      myelogenous leukemia. Decreased adhesion to stroma and fibronectin but increased
      adhesion to the basement membrane components laminin and collagen type IV.
AB  - We studied the adhesion of primitive and committed progenitors from chronic
      myelogenous leukemia (CML) and normal bone marrow to stroma and to several
      extracellular matrix components. In contrast to benign primitive progenitors from
      CML or normal bone marrow, Ph1-positive primitive progenitors from CML bone
      marrow fail to adhere to normal stromal layers and to fibronectin and its
      proteolytic fragments, but do adhere to collagen type IV, an extracellular matrix
      component of basement membranes. Similarly, multilineage colony-forming unit (CFU
      MIX) progenitors from CML bone marrow do not adhere to fibronectin or its
      adhesion promoting fragments but adhere to collagen type IV. Unlike committed
      progenitors from normal bone marrow, CML single-lineage burst-forming units
      erythroid and granulocyte/macrophage colony-forming units fail to adhere to
      fibronectin or its components but do adhere to both collagen type IV and laminin.
      Evaluation of adhesion receptor expression demonstrates that fibronectin
      receptors (alpha 4, alpha 5, and beta 1) are equally present on progenitors from
      normal and CML bone marrow. However, a fraction of CML progenitors express alpha
      2 and alpha 6 receptors, associated with laminin and collagens, whereas these
      receptors are absent from normal progenitors. These observations indicate that
      the premature release of malignant Ph1-positive progenitors into the circulation
      may be caused by loss of adhesive interactions with stroma and/or fibronectin and
      acquisition of adhesive interactions with basement membrane components. Further
      study of the altered function of cell-surface adhesion receptors characteristic
      of the malignant clone in CML may lead to a better understanding of the
      mechanisms underlying both abnormal expansion and abnormal circulation of
      malignant progenitors in CML.

PMID- 1383272
TI  - Human melanoma cells derived from lymphatic metastases use integrin alpha v beta
      3 to adhere to lymph node vitronectin.
AB  - Human melanoma is a highly metastatic cancer and the regional lymph nodes are
      generally the first site of metastasis. Adhesion to cryostat sections of human
      lymph nodes was therefore studied using two human melanoma models established
      from lymph node metastases, namely, MeWo cell lines of diverse metastatic
      potentials and a highly metastatic cell line of recent origin designated MIM/8.
      We found a good correlation between the metastatic potentials of the melanoma
      cells as measured in nude mice and their ability to adhere to cryostat sections
      of human lymph nodes. When adhesion to immobilized extracellular matrix proteins
      was measured, a significant increase in adhesion, which correlated with increased
      metastasis, was seen mainly on vitronectin and to a lesser extent on fibronectin.
      The adhesion to vitronectin and to the frozen sections were specifically blocked
      by an RGD-containing peptide, mAb 661 to vitronectin and mAb LM609 to integrin
      alpha v beta 3. FACS analysis revealed a significant and specific increase in
      cell surface expression of alpha v beta 3 on the metastatic cells as compared to
      the parent line. Together these results suggest that the adhesion of melanoma
      cells to lymph node vitronectin via the alpha v beta 3 receptor plays a role in
      the process of lymphatic dissemination.

PMID- 1383273
TI  - Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage
      recognition of neutrophils undergoing apoptosis.
AB  - We have investigated the cell surface recognition mechanisms used by human
      monocyte-derived macrophages (M phi) in phagocytosis of intact aging human
      neutrophils (PMNs) undergoing apoptosis. This study shows that the adhesive
      protein thrombospondin (TSP) was present in the interaction, both associated with
      the M phi surface and in solution at a mean concentration of 0.59 micrograms/ml.
      The interaction was inhibited by treatment of M phi (but not aged PMN) with
      cycloheximide, but could be "rescued" by replenishment with exogenous TSP. Under
      control conditions, M phi recognition of aged PMNs was specifically potentiated
      by purified platelet TSP at 5 micrograms/ml, present either in the interaction or
      if preincubated with either cell type, suggesting that TSP might act as a
      "molecular bridge" between the two cell types. In support, both aged PMN and M
      phi were found to adhere to TSP, and phagocytosis of aged PMN was specifically
      inhibited by (a) excess soluble TSP; (b) antibodies to TSP that also inhibit TSP
      mediated adhesion to aged PMN; and (c) down-regulation of M phi receptors for TSP
      by plating M phi on TSP-coated surfaces. Furthermore, inhibition with mAbs/Arg
      Gly-Asp-Ser peptide of the candidate M phi receptors for TSP, CD36, and alpha v
      beta 3 exerted synergistic effects on both M phi recognition of aged PMN and M
      phi adhesion to TSP, indicating that "two point" adhesion of TSP to these M phi
      structures is involved in phagocytosis of aged PMN. Our findings indicate newly
      defined roles for TSP and CD36 in phagocytic clearance of senescent neutrophils,
      which may limit inflammatory tissue injury and promote resolution.

PMID- 1383274
TI  - Isolation and partial characterization of a specific alpha-fetoprotein receptor
      on human monocytes.
AB  - Since a large body of data has suggested a significant role for alpha-fetoprotein
      (AFP) in the regulation of the immune response at a number of levels, we examined
      the possibility of a specific receptor for AFP on the immune recognition cell,
      the monocyte/macrophage. Microscopic autoradiography exhibited an obvious binding
      of AFP almost exclusively on human peripheral monocytes but not on lymphocytes.
      In a human monocyte cell line (U937) Scatchard plot analysis indicated the
      presence of two distinct AFP-specific binding sites with a Kd of 5 x 10(-11) M,
      49 binding sites per cell, and 2.5 x 10(-7) M, 7,800 binding sites per cell. 125I
      ASD-AFP, AFP-radiolabeled bifunctional photoactivatable thio-cleavable cross
      linker, was used to isolate the AFP binding protein from U937 cells. After
      ultraviolet photoactivation, 125I-sulfosuccinimidyl 2-(p-azido-salicylamido)ethyl
      1,3'-dithiopropionate was covalently linked to the putative receptor.
      Autoradiography of SDS gradient PAGE under reducing conditions showed a major
      radiolabeled band at between 62 and 65 kD. To confirm the specificity of the
      finding, recombination of AFP with the isolated receptor was examined in
      artificially reconstituted membrane vesicles, which also resulted in a single
      band at approximately 62-65 kD by SDS-PAGE autoradiography. From the data above,
      we concluded that human monocytes possess a specific AFP binding protein on the
      membrane, a putative receptor, which may be involved with the physiological
      regulation of the immune response.

PMID- 1383275
TI  - Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle
      acetylcholine receptor.
AB  - In myasthenia gravis (MG) an autoimmune response against muscle acetylcholine
      receptor (AChR) occurs. Embryonic muscle AChR contains a gamma subunit,
      substituted in adult muscle by a homologous epsilon subunit. Antibodies and CD4+
      cells specific for embryonic AChR have been demonstrated in MG patients. We
      identified sequence segments of the human gamma subunit forming epitopes
      recognized by four embryonic AChR-specific CD4+ T cell lines, propagated from MG
      patients' blood by stimulation with synthetic peptides corresponding to the human
      gamma subunit sequence. Each line had an individual epitope repertoire, but two
      20-residue sequence regions were recognized by three lines of different HLA
      haplotype. Most T epitope sequences were highly diverged between the gamma and
      the other AChR subunits, confirming the specificity of the T cells for embryonic
      AChR. These T cells may have been sensitized against AChR expressed by a tissue
      other than innervated skeletal muscle, possibly the thymus, which expresses an
      embryonic muscle AChR-like protein, containing a gamma subunit. Several sequence
      segments forming T epitopes are similar to regions of microbial and/or mammalian
      proteins unrelated to the AChR. These findings are consistent with the
      possibility that T cell cross-reactivity between unrelated proteins ("molecular
      mimicry"), proposed as a cause of autoimmune responses, is not a rare event.

PMID- 1383276
TI  - Granulosa cell-derived insulin-like growth factor (IGF) binding proteins are
      inhibitory to IGF-I hormonal action. Evidence derived from the use of a truncated
      IGF-I analogue.
AB  - An increasing body of information now suggests that insulin-like growth factor
      (IGF) binding proteins (BPs) may serve as antigonadotropins at the level of the
      ovary. It is the objective of the present communication to evaluate the
      functional role of endogenous (granulosa cell-derived) IGFBPs by exploiting the
      unique properties of des(1-3)IGF-I, a naturally occurring IGF-I analogue
      characterized as a weak ligand of IGFBPs but not of type I IGF receptors. Given
      IGFBP-replete circumstances, des(1-3)IGF-I proved more potent (10-fold) than its
      intact counterpart in promoting the follicle stimulating hormone (FSH)-stimulated
      accumulation of progesterone by cultured rat granulosa cells. In contrast, des(1
      3)IGF-I proved virtually equipotent to the unmodified principle under IGFBP
      deplete circumstances. Taken together, these findings are in keeping with the
      notion and that the apparently enhanced potency of des(1-3)IGF-I (under IGFBP
      replete conditions) is due to its diminished affinity for endogenously generated
      IGFBPs and that rat granulosa cell-derived IGFBPs are inhibitory to IGF (and thus
      inevitably to gonadotropin) hormonal action. Accordingly, the reported ability of
      gonadotropins to attenuate IGFBP release by granulosa cells may be designed to
      enhance the bioavailability of endogenously generated IGFs in the best interest
      of ovarian steroidogenesis.

PMID- 1383277
TI  - Neutrophil-dependent acute lung injury. Requirement for P-selectin (GMP-140).
AB  - Rapid translocation of P-selectin (GMP-140) from cytoplasmic granules to the cell
      membrane of endothelial cells promotes adhesive interactions with neutrophils
      which, when activated, damage the endothelium. The role of P-selectin in lung
      vascular endothelial injury in rats after systemic activation of complement by
      intravenous infusion of cobra venom factor has been assessed. Within 5-10 min
      after cobra venom factor infusion, the pulmonary vasculature demonstrated
      immunohistochemical expression of an epitope that reacts with anti-human P
      selectin. Monoclonal antibody to human P-selectin blocked in vitro adherence of
      rat or human platelets (activated with thrombin) to neutrophils and was
      demonstrated to react with thrombin-activated rat platelets. The antibody did not
      react with rat neutrophils. In vivo, the antibody had strongly protective effects
      against cobra venom factor-induced pulmonary vascular injury as determined by
      permeability changes and hemorrhage. In parallel, lung myeloperoxidase content
      was greatly reduced and, by transmission electron microscopy, there was markedly
      diminished adherence of neutrophils to the pulmonary vascular endothelium and
      much diminished injury of endothelial cells, as defined by hemorrhage. These data
      indicate that anti-human P-selectin reacts with a pulmonary vascular antigen in
      rats and that this antigen is essential for the full expression of lung injury.

PMID- 1383279
TI  - Parents developmental perceptions and expectations for their high-risk infants.

PMID- 1383280
TI  - Histology of normal haemopoiesis: bone marrow histology. I.

PMID- 1383278
TI  - Requirement of pp60c-src expression for osteoclasts to form ruffled borders and
      resorb bone in mice.
AB  - Targeted disruption of the c-src proto-oncogene in mice has shown that src
      expression is required for normal bone resorption, since the src-deficient
      mutants develop osteopetrosis. To evaluate the mechanisms by which src-deficiency
      affects osteoclast function, we treated src-deficient mice with the stimulants of
      bone resorption, IL-1, parathyroid hormone, and parathyroid hormone-related
      protein, and analyzed the effects by quantitative bone histomorphometry and
      electron microscopy. Increased numbers of multinucleated cells with the
      morphological characteristics of osteoclasts appeared on bone surfaces, but these
      cells did not form ruffled borders or normal resorption lacunae. To confirm these
      in vivo findings, we cultured src-mutant bone marrow cells on dentine slices in
      the presence of 1,25 dihydroxyvitamin D3. Increased numbers of multinucleated
      cells were formed, but unlike normal murine bone marrow cells, they did not form
      resorption pits. These results indicate that osteoclasts appear in the absence of
      pp60c-src, but that pp60c-src expression is required for mature osteoclasts to
      form ruffled borders and resorb bone.

PMID- 1383281
TI  - Substance P immunoreactive boutons form synapses with feline sympathetic
      preganglionic neurons.
AB  - In this study, the relationship between substance P-immunoreactive boutons and
      antidromically activated sympathetic preganglionic neurons was examined by light
      and electron microscopy. Sympathetic preganglionic neurons in the T2-T4 spinal
      segments of the cat were identified by intracellular recording and antidromic
      activation from the corresponding white ramus. Neurons were filled with lucifer
      yellow and then stained to reveal, simultaneously, substance P and lucifer yellow
      immunoreactivity. All of the neurons examined with the light microscope (n = 13)
      received appositions from substance P-immunoreactive boutons. Appositions were
      found on all parts of the neuron, including the somata, dendrites, and axon
      initial segment. In most cases (11/13) few close appositions were seen; however,
      two neurons received large numbers of appositions from substance P-immunoreactive
      boutons. On one neuron, 16 substance P-immunoreactive varicosities that were
      identified as being closely apposed at the light microscope level were serially
      sectioned and examined with the electron microscope. Of these 16 varicosities,
      eight either directly contacted the neuron or formed morphologically identifiable
      synapses. The remaining eight varicosities were separated from the neuron by thin
      glial processes. Two other sympathetic preganglionic neurons that were examined
      ultrastructurally also received substance P-immunoreactive synapses and close
      contacts. These findings suggest that substance P-containing nerve fibres could
      affect all sympathetic preganglionic neurons but are likely to be important in
      regulating the activity of only a small proportion of these neurons.

PMID- 1383283
TI  - Cingulate input to the primary and supplementary motor cortices in the rhesus
      monkey: evidence for somatotopy in areas 24c and 23c.
AB  - We examined the distribution of cingulate projections to the somatotopically
      related parts of the primary (M1) and supplementary (M2) motor cortices of the
      monkey by using fluorescent dyes. Labeled neurons were found in layers 3, 5 and 6
      of areas 24c and 23c and were heaviest following injections placed in M2.
      Projections to analogous somatotopic areas in M1 and M2 arose from similar
      cingulate regions. In area 24c, neurons projecting to the face area of M1 and M2
      were located anteriorly, those to the hindlimb were located posteriorly, and
      neurons projecting to the forelimb area of M1 and M2 were located in between. In
      area 23c, neurons projecting to the forelimb area of M1 and M2 were located
      anteriorly and those to the hindlimb area of M1 and M2 were located posteriorly.
      The face area of M1 and M2 was not found to receive afferents from area 23c. In
      contrast to this discreteness, cingulate projections to Woolsey's axial
      representation of M1 were diffuse. The results support the presence of a separate
      and somatotopically organized cingulate motor cortex in area 24c. This is
      predicated on the facts that: (1) small injections of retrograde tracers placed
      in analogous somatotopic parts of M1 and M2 resulted in similar patterns of
      labeling within the electrophysiologically "excitable" portion of the anterior
      cingulate cortex, and (2) this organized topography infers somatotopy. Our data
      fail to support a somatotopically organized cingulate motor area in area 23c if
      the criterion of all body parts is demanded. By virtue of its anatomical location
      and its connectional relation to the spinal cord and isocortical motor fields on
      the one hand and to the limbic cortex on the other, area 24c may be considered as
      M3 and provide limbic influences at several levels of motor control.

PMID- 1383282
TI  - Inhibitory synaptic input to identified rubrospinal neurons in Macaca
      fascicularis: an electron microscopic study using a combined immuno-GABA-gold
      technique and the retrograde transport of WGA-HRP.
AB  - Rubrospinal neurons of the magnocellular division of the red nucleus of Macaca
      fascicularis were retrogradely labeled following spinal cord microinjections of
      wheat germ agglutinin-horseradish peroxidase, as demonstrated by the chromagen
      tetramethylbenzidine, identifying the mesencephalic cells of origin of this
      descending motor pathway. The tissue was processed for electron microscopy and
      subsequently tested on the electron microscope grid for immunoreactivity of gamma
      aminobutyric acid (GABA) in presumed local circuit neuronal somata, in dendrites,
      and in axonal terminals. Results demonstrate the presence of retrogradely labeled
      rubrospinal neurons of medium and large diameters (30-90 microns) and
      immunoreactive neurons of small size (less than 20 microns in diameter) within
      the nucleus. In addition, there are substantial numbers of GABAergic, presumably
      inhibitory, synaptic structures contacting somata and primary, medium, and small
      sized dendrites, as well as spineheads of rubrospinal neurons. The immunoreactive
      presynaptic profiles exhibit two different morphological appearances: one axonal
      and the other dendritic. Axonal terminals contain densely packed pleomorphic to
      flattened vesicles and form primarily symmetrical synapses with somata and all
      regions of the dendritic arbor. GABAergic profiles resembling presynaptic
      dendrites (PSDs) are also present. These profiles possess scattered flattened to
      pleomorphic synaptic vesicles in a translucent cytoplasm and are often
      postsynaptic to axonal terminals of unknown origin, or to GABAergic profiles.
      GABAergic local circuit neurons (LCNs), the neurites of which remain within the
      confines of the nucleus, appear to be contacted primarily by cortical and
      cerebellar afferents. These LCNs may or may not possess axons and thus may
      represent both the source of the GABAergic axonal terminals as well as that of
      the PSDs. Inhibitory afferents from other sources, such as the mesencephalic
      reticular formation, may also account for GABAergic terminals involved in this
      inhibition. We propose that the level of excitability of rubrospinal neurons and
      their subsequent activation of spinal motor neurons and interneurons is
      significantly regulated by the local circuit GABAergic inhibitory interneuronal
      population of the nucleus proper and probably by axons entering the nucleus from
      an extranuclear source.

PMID- 1383284
TI  - Selective innervation of foreign muscles following damage or removal of normal
      muscle targets.
AB  - The restoration of a normal pattern of neural connectivity following nerve injury
      depends upon the selective reinnervation of appropriate postsynaptic targets.
      Previous studies suggest that, in the neuromuscular system, recognition between
      regenerating motoneurons and target muscles depends upon the positions of origin
      of the motoneurons and muscles. In axolotls, portions of the motor pools of
      adjacent muscles overlap. We found that, following removal of a pair of adjacent
      hindlimb muscles, anterior and posterior iliotibialis, many regenerating
      iliotibialis motor axons invaded foreign muscles. A more anterior foreign muscle,
      puboischiofemoralis internus, received greater innervation from anterior
      iliotibialis motoneurons, whereas a more posterior muscle, iliofibularis,
      received greater innervation from posterior iliotibialis motoneurons.
      Furthermore, anterior iliotibialis motoneurons that reinnervated
      puboischiofemoralis internus occupied the rostral portion of anterior
      iliotibialis motor pool, which overlaps that of puboischiofemoralis internus.
      Anterior iliotibialis motoneurons that reinnervated iliofibularis occupied the
      caudal portion of the anterior iliotibialis motor pool, which overlaps that of
      iliofibularis. When both anterior and posterior iliotibialis were damaged so that
      their myofibers were permanently destroyed, the rostrocaudal origins of the
      motoneurons that reinnervated them were virtually the same, suggesting that the
      motoneurons had difficulty distinguishing between the myofiberless iliotibialis
      muscles. However, some iliotibialis motoneurons invaded puboischiofemoralis
      internus instead of their myofiberless targets. Puboischiofemoralis internus
      received more innervation from the anterior iliotibialis motoneurons than the
      positionally less appropriate posterior iliotibialis motoneurons. These data are
      consistent with the hypothesis that selective reinnervation of muscle depends
      upon a system of recognition cues based on position.

PMID- 1383285
TI  - Serotoninergic medullary raphespinal projection to the lumbar spinal cord in the
      rat: a retrograde immunohistochemical study.
AB  - Classically the raphespinal system has been regarded as a serotoninergic system;
      inhibition of spinal nociceptive transmission produced by stimulation of the
      medullary raphe nuclei is mediated partially by spinal serotoninergic receptors.
      However, recent evidence suggests that the raphe nuclei are not homogeneous
      populations of serotoninergic cells. The objective of the present study was to re
      examine, in the rat, the serotoninergic raphespinal projection to the lumbar
      spinal cord, and to determine the relative contribution of serotoninergic
      raphespinal neurons to the total population of raphespinal neurons.
      Microinjections of wheat-germ agglutinin horseradish peroxidase conjugate coupled
      to colloidal gold into the lumbar spinal cord resulted in the retrograde labeling
      of 53% and 59% of the serotoninergic neurons in the raphe nuclei and in the para
      raphe zone, respectively. Conversely, 47% and 28% of the retrogradely labeled
      neurons in the raphe and para-raphe zone, respectively, demonstrated serotonin
      like immunoreactivity. Thus, contrary to previous reports, the present results
      suggest 1) that only about half of the serotoninergic neurons in the raphe nuclei
      and in the surrounding para-raphe zone project to the lumbar spinal cord, and 2)
      that a large proportion of the neurons in the raphe nuclei (53%) and in the
      surrounding para-raphe zone (72%) that project to the lumbar spinal cord are not
      serotoninergic.

PMID- 1383286
TI  - Organization of the septal organ projection to the main olfactory bulb in adult
      and newborn rats.
AB  - The septal organ, which is regarded as an olfactory subsystem, is a small patch
      of sensory epithelium located ventral to the main olfactory sheet on the septal
      wall of the nasal cavity. The only consensus to date regarding some proper area
      of projection of this subsystem is that the septal organ projects to the medial
      aspect of the main olfactory bulb. The purpose of our study was to analyze
      precisely the topographical organization of the bulbar projection of the septal
      organ in adult rats and in 3- to 15-day-old rats following WGA-HRP placements at
      the level of the septal epithelium. Results show that the septal organ projects
      exclusively to the posterior half of the main olfactory bulb and its projection
      area is mainly restricted to the ventromedial bulbar aspect. When the septal
      organ was fully injected, the pattern of bulbar projection was characterized by
      two types of glomerular labeling: 1) presence of single heavily labeled glomeruli
      identified as "septal" glomeruli, since they were mainly built up by afferents
      coming from the septal organ and (2) presence of a thin network of labeled septal
      fibers distributed in glomeruli which were mainly formed by afferents coming from
      the main olfactory epithelium. Although the pattern of mucosobulbar projection of
      the septal organ is already established in newborns, a significant increase in
      the number of "septal" glomeruli occurs during the first 15 postnatal days.
      Anatomical data indicate that even if the projection of the septal organ does not
      appear completely segregated in the olfactory bulb, this projection is not either
      exactly similar to that of the main olfactory epithelium.

PMID- 1383288
TI  - Cortical connections of subdivisions of inferior temporal cortex in squirrel
      monkeys.
AB  - Patterns of cortical connections and architectonics were used to determine
      subdivisions of inferior temporal (IT) cortex of squirrel monkeys. Single or
      multiple injections of the tracers wheat germ agglutinin-horseradish peroxidase,
      Fast Blue, Diamidino Yellow, Fluoro-Gold, and 3H-amino acids were placed into IT
      cortex. Most injections were placed in caudal IT cortex in the region previously
      shown to receive input from the caudal subdivision of the Dorsolateral Area, DLC;
      additional injections were placed in more rostral IT cortex. The results indicate
      the presence of two major regions: a caudal region, ITC, and a rostral region,
      ITR. An intermediate region of cortex along the ITC-ITR border that displays some
      connections of ITC and some connections of ITR may be another area. ITC contains
      a more myelinated dorsal area, ITCd, and a larger ventral area, ITCv. Both ITCd
      and ITCv receive a major projection from DLC; additional input from DLR, MT, and
      VII; and send strong projections to ITR, the lateral bank of the superior
      temporal sulcus, and dorsolateral prefrontal cortex. Only ITCd has strong
      connections with DLR and cortex in the depths of the superior temporal sulcus,
      and only ITCv has connections with lateral orbital cortex. The overall pattern of
      connections between ITC and DLC suggests that ITC has a crude topographic
      organization, with dorsal cortex representing the lower field and ventral cortex
      representing the upper field. ITR differs from ITC by receiving little if any
      input from DLC; projecting to inferior temporal polar cortex, the rostral Sylvian
      fissure, and medial orbital cortex; and having a less distinct layer IV.
      Comparison of subdivisions of inferior temporal cortex defined in the present
      study in squirrel monkeys and those reported in other primates suggests that ITC
      of squirrel monkeys may correspond to area TEO of macaque monkeys.

PMID- 1383287
TI  - The afferent and efferent connections of the nucleus submedius in the rat.
AB  - The afferent and efferent connections of the nucleus submedius (Sm) in the medial
      thalamus of the rat were examined. Injections of wheat-germ agglutinin conjugated
      horseradish peroxidase (WGA-HRP) into the Sm resulted in dense terminal labeling
      in the middle layers of the ipsilateral ventrolateral orbital cortex (VLO). Less
      dense labeling was also observed in the superficial and deep layers of VLO and in
      the medial part of the lateral orbital cortex (LO) and in the contralateral VLO.
      Retrogradely labeled neurons were observed primarily in the deep layers of VLO
      and the dorsal peduncular cortex (DP). Labeled neurons were also observed
      bilaterally, in the nucleus of the horizontal limb of the diagonal band, the
      lateral hypothalamus, the thalamic reticular nucleus (Rt), medial parabrachial
      nucleus (MPB), and the laterodorsal tegmental nucleus (LDT). Many labeled neurons
      were also observed in the trigeminal brain-stem complex. Injections of Fluoro
      Gold (FG) into Sm resulted in a very similar distribution of retrogradely labeled
      neurons. Injections of WGA-HRP and FG in the orbital cortex confirmed the
      ipsilateral Sm projection to VLO and suggested that the middle and deep layers of
      VLO receive a specific ipsilateral projection from the dorsal Sm and that the
      superficial layers receive a projection primarily from the ventral Sm. Injections
      of WGA-HRP into the lateral hypothalamus, LDT, and MPB confirmed the retrograde
      labeling findings; the lateral hypothalamus was found to send a projection to the
      medial Sm, the LDT region to the ventromedial Sm and the MPB to the medial and
      dorsal Sm. These findings confirm and extend the results of previous studies in
      cat and rat indicating that Sm has a major and specific reciprocal connection
      with VLO. This finding, in conjunction with previous studies showing direct
      spinal and trigeminal inputs and the existence of nociceptive neurons in Sm and
      VLO, provides further support for a role of Sm in nociception.

PMID- 1383289
TI  - Musculotopic organization of the hypoglossal nucleus in the cynomolgus monkey,
      Macaca fascicularis.
AB  - The movements of the tongue in feeding and vocalization are enabled by a complex
      system of interdigitated muscle fibers in the tongue body. Because of this
      complexity, the detailed anatomical connections between individual intrinsic
      tongue muscles and corresponding motoneurons in the hypoglossal nucleus have not
      been described for any mammal. In this study we describe the distribution of
      retrogradely labeled neurons in the hypoglossal nucleus, following injections of
      wheat-germ agglutinin-horseradish peroxidase into different regions of the tongue
      of 21 cynomolgus monkeys. These experiments demonstrate a spatial organization of
      hypoglossal motoneurons that reflects the anatomical and functional organization
      of tongue body muscles: motoneurons innervating the transversus and verticalis
      muscles are located in medial hypoglossal nucleus regions, motoneurons
      innervating the genioglossus are located in intermediate hypoglossal nucleus
      regions, motoneurons innervating the hyoglossus and inferior longitudinalis are
      located in ventrolateral hypoglossal nucleus regions, and motoneurons innervating
      the styloglossus and superior longitudinalis are located in dorsolateral
      hypoglossal nucleus regions. Motoneurons innervating the suprahyoid muscle, the
      geniohyoid, are situated in a cell column separated ventrally from the main body
      of the hypoglossal nucleus. Motoneurons innervating the palatoglossus are located
      in the nucleus ambiguus and, possibly, in dorsolateral hypoglossal nucleus
      regions. Motoneurons of the medial divisions of the hypoglossal nucleus innervate
      tongue muscles that are oriented in planes transverse to the long axis of the
      tongue whereas motoneurons of the lateral divisions innervate tongue muscles that
      are oriented parallel to this axis. These results suggest that the segregation of
      motoneurons corresponds to the functional distinction between tongue protrusion
      and retrusion.

PMID- 1383290
TI  - New metrics for analysis of dendritic branching patterns demonstrating
      similarities and differences in ON and ON-OFF directionally selective retinal
      ganglion cells.
AB  - The morphology and dendritic branching patterns of retinal ganglion cells have
      been studied in Golgi-impregnated, whole-mount preparations of rabbit retina.
      Among a large number of morphological types identified, two have been found that
      correspond to the morphology of ON and ON-OFF directionally selective (DS)
      ganglion cells identified in other studies. These two kinds of DS ganglion cell
      are compared with each other, as well as with examples of class I, class II, and
      class III cells, defined here with reference to our previous studies. Cell body,
      dendritic field size and branching pattern are analyzed in this paper and levels
      of dendritic stratification are examined in the following paper. ON DS ganglion
      cells are about 10% larger in soma size and about 5 times the dendritic field
      area of ON-OFF DS ganglion cells, when compared at the same retinal location.
      These two morphological types of ganglion cell can be said to define the upper
      and lower bounds of an intermediate range of cell body and dendritic field sizes
      within the whole population of ganglion cells. Nevertheless, in previous
      physiological studies receptive field sizes of the two types were shown to be
      similar. This discrepancy between morphological and physiological evidence is
      considered in the Discussion in terms of a model of the excitatory receptive
      field of ON-OFF DS ganglion cells incorporating starburst amacrine cells. A new
      set of metrics is introduced here for the quantitative analysis and
      characterization of the branching pattern of neuronal arborizations. This method
      compares the lengths of terminal and preterminal dendritic branches (treated
      separately), as a function of the distances of their origins from the soma,
      viewed graphically in a two-dimensional scatter plot. These values are derived
      from computer-aided 3D logging of the dendritic trees, and distance from the soma
      is measured as the shortest distance tracked along the dendritic branches. From
      these metrics of the "branch length distributions," scale-independent branching
      statistics are derived. These make use of mean branch lengths and distances,
      slopes of lines fitted to the distributions, and elliptical indices of scatter in
      the distributions. By these measures, ON and ON-OFF DS ganglion cells have
      similar branching patterns, which they share to varying degrees with functionally
      unrelated class III.1 ganglion cells. The scale of the branching patterns of ON
      and ON-OFF DS cells and their degree of uniformity are different,
      however.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1383291
TI  - Dendritic co-stratification of ON and ON-OFF directionally selective ganglion
      cells with starburst amacrine cells in rabbit retina.
AB  - The morphology, dendritic branching patterns, and dendritic stratification of
      retinal ganglion cells have been studied in Golgi-impregnated, whole-mount
      preparations of rabbit retina. Among a large number of morphological types
      identified, two have been found that correspond to the morphology of ON and ON
      OFF directionally selective (DS) ganglion cells identified in other studies.
      These cells have been characterized in the preceding paper in terms of their cell
      body size, dendritic field size, and branching pattern. In this paper, the two
      kinds of DS ganglion cell are compared in terms of their levels of dendritic
      stratification. They are compared with each other and also with examples of class
      III.1 cells, defined in the preceding paper with reference to our previous
      studies. Studies employing computer-aided, 3D reconstruction of dendritic trees,
      as well as analysis of a pair of ON DS and ON-OFF DS ganglion cells with
      overlapping dendritic trees show that the two types of DS ganglion cell partly co
      stratify in the middle of sublamina b (stratum 4). The report that some ON DS
      ganglion cells extend a few dendrites into sublamina a is confirmed. The study of
      pairs of ON-OFF DS ganglion cells and starburst amacrine cells with overlapping
      dendritic trees reveals a precise co-stratification of these two cell types, and
      many points of close apposition of starburst boutons with ON-OFF DS ganglion cell
      dendrites in both sublaminae of the inner plexiform layer (IPL). This is
      confirmed by high-resolution light microscopy and by electron microscopy. It is
      possible to conclude, therefore, that ON DS are also partly co-stratified with
      type b starburst (cholinergic) amacrine cells, and are apparently also partly co
      stratified with type a starburst amacrine cells, when occasional dendrites rise
      to that level. The co-stratification of the two kinds of DS ganglion cell is
      consistent with the sharing of some inputs in common, including some cone bipolar
      cell inputs. The co-stratification of both with starburst amacrine cells agrees
      with the physiological demonstration of the powerful pharmacological effects upon
      ON and ON-OFF DS ganglion cells reported for cholinergic agonists. The major
      difference in the dendritic stratification of bistratified ON-OFF DS ganglion
      cells and generally unistratified ON DS ganglion cells is consistent with the
      bisublaminar organization of ON and OFF pathways in the IPL. The problem of
      occasional branches of ON DS cells in sublamina a is discussed in terms of a
      threshold for OFF responses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1383292
TI  - Projections from the laterodorsal nucleus of the thalamus to the limbic and
      visual cortices in the rat.
AB  - The laterodorsal nucleus (LD) of the thalamus is an important source of thalamic
      afferents to the limbic cortex, but the topography and lamination of these
      projections has not been investigated in detail. Using the anterograde transport
      of Phaseolus vulgaris leucoagglutinin and Fluoro-Ruby, the present study
      demonstrates that in the rat, LD projects to infraradiata, precentral agranular,
      retrosplenial, visual (area 18b), subicular, and entorhinal cortices. Each
      subregion of LD has a distinct pattern of terminals within these cortical areas.
      The rostral part and the dorsalmost part of LD project densely to retrosplenial
      granular a (Rga) cortex, presubiculum and parasubiculum. Slightly more caudal
      parts of dorsal LD project primarily to the postsubiculum. More ventral parts of
      LD project primarily to retrosplenial dysgranular (Rdg) and retrosplenial
      granular b (Rgb) cortices. The projection of LD to area 18b originates from cells
      in the caudalmost part of LD. In each cortical region, LD terminals display
      distinct laminar patterns. In area 18b and the adjacent Rdg cortex, the LD
      terminal field is in layers I, III, and IV, but in both the Rgb and Rga cortices
      the terminal field is located predominantly in layer I. In the postsubiculum the
      LD terminals are distributed to layers I and III/IV and extend into superficial
      layer V; in the presubiculum and the parasubiculum the LD terminals are only in
      the deep layers (i.e., layers IV-VI). A small number of LD axons terminate in the
      deep layers (i.e., layers IV-VI) of the medial entorhinal cortex. These results
      indicate that each area of LD has a distinct projection to limbic and adjacent
      neocortex.

PMID- 1383293
TI  - Therapeutic alternatives in cutaneous T-cell lymphoma.
AB  - Mycosis fungoides and Sezary syndrome, collectively referred to as cutaneous T
      cell lymphoma, are non-Hodgkin's lymphomas that initially appear in the skin.
      Early-stage disease, limited to the skin, is best treated with sequential topical
      therapies such as topical nitrogen mustard, psoralen phototherapy (PUVA), or
      total-skin electron beam therapy. Photopheresis is the first line of therapy for
      the patient with erythroderma. Systemic therapy is generally reserved for
      patients with refractory disease and patients who initially present with
      extracutaneous involvement. Although there are several treatment options for
      cutaneous T-cell lymphoma, there have been few randomized comparative trials.

PMID- 1383294
TI  - Epitopes for CD1a, CD1b, and CD1c antigens are differentially mapped on
      Langerhans cells, dermal dendritic cells, keratinocytes, and basement membrane
      zone in human skin.
AB  - BACKGROUND: CD1 antigens are classified serologically into at least three groups,
      CD1a, CD1b, and CD1c, and many kinds of monoclonal antibodies are available for
      each subgroup of CD1 antigens. CD1a, CD1b, and CD1c antigens have been shown to
      be selectively and differentially expressed on epidermal Langerhans cells and
      dermal dendritic cells in normal human skin. OBJECTIVE: The objective was to
      further delineate the localization of epitopes of CD1 antigens in human skin.
      METHODS: We examined the immunoreactivity of 14 different CD1 antibodies (seven
      CD1a, five CD1b, and two CD1c antibodies) with the immunoperoxidase technique. We
      also studied the reactivity of NU-T2 (CD1b) antibody by immunogold electron
      microscopy. RESULTS: The epitopes for CD1a, CD1b, and CD1c antigens were
      differentially mapped on epidermal Langerhans cells, dermal dendritic cells,
      keratinocytes, the luminal portion of eccrine gland ducts, and the basement
      membrane zone in human skin. CONCLUSION: These CD1 antibodies may be useful to
      analyze the phenotypic alteration of immune and nonimmune cells in various skin
      diseases.

PMID- 1383295
TI  - Increased epidermal growth factor receptors in melanocytic lesions.
AB  - BACKGROUND: Epidermal growth factor receptors (EGF/R) have been reported to be
      absent in melanomas or, in contrast, to be markers for potential malignancy in
      melanocytic lesions. OBJECTIVE: Our purpose was to evaluate the literature
      discrepancies regarding the presence of EGF/R in melanocytic lesions and to
      determine whether EGF/R presence correlates with the potential for malignancy of
      melanocytic lesions. METHODS: An EGF/R-specific polyclonal antibody was used to
      study melanomas, dysplastic nevi, congenital nevi, and nevocellular nevi.
      RESULTS: All melanocytic cell types (nevus and melanoma cells) in the lesions
      studied had immunoreactive EGF/R. EGF/R immunoreactivity was also observed
      throughout the epidermal basal to granular cell layers overlying the melanocytic
      lesions, although dermal fibroblasts were negative. CONCLUSION: The pattern of
      increased immunoreactive EGF/R in both benign and malignant nevocellular lesions
      suggests that although EGF/R are not a specific marker of potential malignancy in
      melanocytic lesions, they may mediate or coordinate growth of keratinocytes and
      nevus cells.

PMID- 1383296
TI  - Lindane-resistant scabies.

PMID- 1383297
TI  - Epidermal Langerhans cells after allogeneic bone marrow transplantation:
      depletion by chemotherapy conditioning regimen alone.
AB  - Depletion of Langerhans cells (LC) is known to follow bone marrow transplantation
      (BMT) and is thought to be mainly related to pretransplant radiation and
      chemotherapy conditioning regimens. We studied sequential biopsies of clinically
      normal skin of 22 thalassemic and leukemic patients undergoing allogeneic BMT who
      had received only chemotherapy (busulfan and cyclophosphamide) as conditioning
      regimen. LC were identified immunohistochemically using antibodies against CD1a
      and HLA-DR antigens, and their number expressed per square mm of epidermal
      vertical section, the latter measured by computerized image analysis. After the
      preparatory regimen, the number of LC decreased progressively in both leukemic
      and thalassemic patients. CD1a+ and HLA-DR+ epidermal cells were reduced,
      respectively, to 68.5% and 64.5% of their original number around Day 2, and to
      23.1% and to 18.2% around Day 17. By this time, electron microscopic examination
      of selected biopsies confirmed the depletion of LC. Variable repopulation was
      observed between Days 40 and 60. Our results indicate that a conditioning regimen
      based exclusively on high dose chemotherapy depletes epidermal LC early after
      BMT, and that such depletion is not related to the development of acute graft
      versus-host disease.

PMID- 1383299
TI  - Harlequin fetus with abnormal lamellar granules and giant mitochondria.
AB  - A case of harlequin ichthyosis was studied with electron microscopy. From the
      basal cell to granular cell layers, keratinocytes contained giant mitochondria
      (860 nm) which exhibited vesicular cristae. Typical lamellar granules were
      absent; instead, numerous dense cored granules (DCG) and particles containing
      cored granules (PCG) were produced. Some of these were discharged into the
      intercellular spaces of granular cells, but the majority failed to be released
      from the cytoplasm. These retained DCG and PCG coalesced to form large vacuoles
      and cavities in the stratum corneum. In the hair follicle, keratinized cells
      failed to loosen and desquamate into the hair canal; instead, they formed
      concentric keratin rings surrounding hair, a diagnostic feature of this disease.
      It is suggested that the abnormal lamellar granule underlies the pathogenesis of
      this disease and that giant mitochondria may be related to an abnormal lipid
      metabolism of keratinocytes which may affect lipid composition of lamellar
      granules.

PMID- 1383300
TI  - Isolation and characterization of alpha 2-macroglobulin from mastitis milk.
AB  - Whey samples were screened for the presence of the proteinase inhibitor alpha 2
      macroglobulin (alpha 2M). From an enzymic test, alpha 2M levels in normal whey
      varied in the range 0.49-0.84% of the serum level, whereas in mastitis whey the
      activity was markedly increased, reaching values between 0.91 and 138.5% (median
      7.2%) of standard serum level. In mastitis milk samples but not in normal milk
      alpha 2M was also detected by double immunodiffusion and Western blotting. The
      proteinase inhibitor was purified from a mastitis milk sample with high alpha 2M
      activity (138.5% of serum level). In SDS-PAGE, native-PAGE and in double
      immunodiffusion analysis the inhibitor appeared indistinguishable from plasma
      derived alpha 2M. The alpha 2M preparation from mastitis whey migrated
      essentially as native alpha 2M, representing the 'slow' form of the molecule.
      Treatment with trypsin transformed the alpha 2M preparation to the
      electrophoretic 'fast' form, but treatment with methylamine had only a minor
      effect. The receptor recognition sites were not exposed on the isolated alpha 2M
      molecule but could be readily exposed by treatment of the proteinase inhibitor
      with trypsin, which further proved that the isolated alpha 2M was in the entire
      native, functionally active state.

PMID- 1383298
TI  - Value of immunohistochemistry in the diagnosis of leukemia cutis: study of 54
      cases using paraffin-section markers.
AB  - A grave prognosis is usually associated with leukemic skin infiltrates (leukemia
      cutis). However, some leukemic skin infiltrates are clinically similar to
      reactive non-leukemic infiltrates in patients with leukemia; thus it is of great
      importance to distinguish them. Fifty-four cases which were thought clinically to
      be leukemia cutis underwent immunophenotyping with a panel of nine T, B,
      monocytic, and macrophage markers using paraffin sections. Immunohistochemistry
      helped identify 44 cases with leukemia cutis and 10 with reactive infiltrates. In
      all cases of leukemia cutis, the staining patterns of skin infiltrates were
      concordant with cell type in the bone marrow. Furthermore, the panel of markers
      was usually helpful in distinguishing reactive from leukemia infiltrates,
      especially in cases with chronic lymphatic leukemia. Immunohistochemistry is a
      valuable adjunct in histopathologic differentiation of skin infiltrates in most
      cases of leukemia. With formalin-fixed, paraffin-embedded biopsies, we recommend
      that CD45 (LCA), CD45RO (UCHL-1), CD3, CD20 (L-26), CD43 (Leu-22), CD68 (KP-1),
      lysozyme, and chloroacetate esterase be considered in cases of systemic leukemia
      with cutaneous papules and nodules that prove difficult to interpret with routine
      section.

PMID- 1383301
TI  - Increased susceptibility to intramammary infection following removal of teat
      canal keratin.
AB  - Influence of teat canal keratin on susceptibility to intramammary infection was
      investigated in lactating Jersey cows. In each of two replicate trials, keratin
      was removed from the left teats of 20 cows immediately before milking.
      Immediately after milking, all teats were exposed to bacterial challenge by
      immersion in a suspension of Streptococcus agalactiae (5 x 10(7) cfu/ml).
      Bacterial challenge was repeated after the next four milkings. Foremilk samples
      were obtained for 8 d after keratin removal to determine infection status. A
      mammary quarter was classified as infected based solely upon the bacteriological
      criteria outlined by the National Mastitis Council. The rate of infection in
      quarters from which keratin was removed was greater than that in control
      quarters. Infection rates were 26.3% for keratin-removed quarters and 8.3% for
      control quarters in trial 1 and 13.5 and 0%, respectively, in trial 2. When more
      stringent criteria (recovery of greater than 100 cfu of S. agalactiae/ml in three
      or more successive milk samples and a SCC of greater than 10(6)) were used to
      identify a subset of infections that were clearly intramammary, infection rates
      were 9.3% for keratin-removed quarters and 1.4% for control quarters. Thus,
      partial removal of keratin from the teat canal compromised the ability of the
      teat to prevent passage of bacterial pathogens from the external environment into
      the mammary gland.

PMID- 1383302
TI  - Hypnosis for the treatment of burn pain.
AB  - The clinical utility of hypnosis for controlling pain during burn wound
      debridement was investigated. Thirty hospitalized burn patients and their nurses
      submitted visual analog scales (VAS) for pain during 2 consecutive daily wound
      debridements. On the 1st day, patients and nurses submitted baseline VAS ratings.
      Before the next day's would debridement, Ss received hypnosis, attention and
      information, or no treatment. Only hypnotized Ss reported significant pain
      reductions relative to pretreatment baseline. This result was corroborated by
      nurse VAS ratings. Findings indicate that hypnosis is a viable adjunct treatment
      for burn pain. Theoretical and practical implications and future research
      directions are discussed.

PMID- 1383303
TI  - Scanning electron microscopy of odontogenic cyst epithelium.
AB  - The epithelial lining of 8 odontogenic keratocysts (OKC), 9 radicular (RC) and 3
      dentigerous cysts (DC) were examined in SEM in order to study the ultrastructural
      surface topography of the lumenal surface cells. The orthokeratinized OKC showed
      a reticular network of intercommunicating microridges surrounding micropits
      giving a honeycombed appearance to the entire surface. The deep surface of these
      cells was covered by a complementary array of short stubby microvilli. This
      pattern was identical to that described for oral epithelium in areas of
      masticatory mucosa. The parakeratinized OKC showed a complex pattern of
      microplications (MP) on both upper and deep cell surfaces. The non-keratinized
      linings of RC and DC revealed a similar MP pattern but of a less complex nature.
      The MP pattern of cells from para- and non-keratinized cysts was identical to
      that described for oral epithelial cells from lining mucosa. The surface
      ultrastructure of ciliated, mucus and brush cells occurring in RC was found to be
      indistinguishable from that described in the mammalian respiratory tract. The MP
      pattern forms part of the cellular interdigitation mechanisms in stratified
      squamous epithelium. Differences in the ultrastructural configuration are related
      to the type of epithelium in terms of keratinization rather than to protective
      functions.

PMID- 1383304
TI  - Interactions of delmopinol with constituents of experimental pellicle.
AB  - The prolonged retention of an effective chemotherapeutic agent on oral surfaces
      and in dental plaque aids in plaque control. The objective of this study was to
      investigate interactions between delmopinol, a morpholinoethanol derivative, and
      experimental pellicle. Hydroxyapatite beads were coated with different
      constituents of pellicle (e.g., saliva, carbohydrates, cell-free enzymes, and
      bacteria). Delmopinol demonstrated a higher affinity for saliva-coated
      hydroxyapatite (sHA) and for experimental pellicle coated with in situ
      synthesized glucans than for untreated hydroxyapatite. High-molecular-weight (MW)
      dextran but not low-MW dextran interfered with the adsorption of delmopinol to
      sHA. Delmopinol did not compete with dextran for the same binding sites on sHA,
      nor did it compete with saliva for the same binding sites on untreated
      hydroxyapatite. Delmopinol inhibited the activity of cell-free
      fructosyltransferase adsorbed onto sHA. In addition, synthesis of glucans by
      Streptococcus mutans adsorbed onto sHA was significantly reduced in the presence
      of delmopinol.

PMID- 1383305
TI  - Blood vessels and immunoreactive substance P-containing nerve fibers in rat skin
      treated topically with clobetasol propionate, a corticosteroid.
AB  - After applying topically a cream (0.1 ml) containing corticosteroid (clobetasol
      propionate), on rat back skin, we examined the morphological alterations of blood
      vessels, substance P-containing nerve fibers, and cutaneous mast cells. After 3,
      6, 10, 15, 30, and 60 min and 4 h, the skin treated was cut out with a sharp
      knife after killing the animals. The skin pieces were processed into conventional
      histological sections cut vertically and examined by staining
      immunohistochemically with anti-substance P serum, by staining with toluidine
      blue for mast cell granules, and by estimating morphometrically the average areas
      of vascular cavity and the number of substance P fibers in the dermis. In the
      dermis and subcutaneous tissue of untreated skin, we found many immunoreactive SP
      containing nerve fibers and mast cells in close association. Three to ten min
      after the treatment, the average area of the vascular cavities steadily
      increased, and SP-positive fibers became less frequent in the dermis. In
      concomitant with those events, cutaneous mast cells discharged their granules.
      Thereafter, the average area of vascular cavities gradually decreased to a
      minimum at 4 h after the treatment. In contrast, both SP-containing fibers and
      mast cells reestablished their initial states after the same duration.

PMID- 1383306
TI  - Increased number of immunoreactive nerve fibers in atopic dermatitis.
AB  - The presence of immunologic markers for neurofilaments, neuropeptides of sensory
      nerve fibers (Calcitonin gene-related peptide and substance P), for noradrenergic
      innervation (neuropeptide Y and Tyrosine hydroxylase), and Neuron-specific
      protein 9.5 was evaluated in frozen tissue sections from normal skin (n = 34) and
      from skin biopsies manifesting urticaria (n = 6), leukocytoclastic vasculitis (n
      = 4), systemic lupus erythematosus (n = 23), and atopic dermatitis (n = 40, of
      which 16 were from lesions induced by epicutaneous atopic allergen patch tests).
      In some normal skin specimens immunoreactive nerve fibers expressing Neuron
      specific protein 9.5 were observed in the epidermis, dermis, and around blood
      vessels. For the other markers, immunolabeling was mainly observed in the dermis
      around blood vessels. Neurofilaments, which are scarce in normal skin epidermis,
      were present in higher density in the epidermis of affected skin in all disease
      conditions. Biopsies from urticaria and systemic lupus erythematosus showed a
      decrease in density of fibers immunolabeled for neuropeptides substance P and
      Calcitonin gene-related peptide and for Neuropeptide Y. In biopsies from skin
      with atopic dermatitis, an increased density of fibers was observed for all
      markers except Neuropeptide Y and Tyrosine hydroxylase. In this group, biopsies
      from positive atopic allergen patch tests showed an enhanced density of fibers
      labeled by antibody to Neuron-specific protein 9.5 and a lower density in
      labeling for Tyrosine hydroxylase. The data indicate a potential role of
      innervation and neuropeptides in dermatoses like atopic dermatitis.

PMID- 1383307
TI  - Substance P and beta-endorphin-like immunoreactivity in lavage fluids of subjects
      with and without allergic asthma.
AB  - Six atopic subjects with grass pollen allergy and six nonallergic healthy
      volunteers were enrolled into this study. Substance P-like immunoreactivity (SP
      LIR) and beta-endorphin-like immunoreactivity (beta E-LIR) were determined in
      bronchoalveolar lavage (BAL) and nasal lavage (NAL) fluids before and after
      allergen (grass pollen) provocation. A significant increase in the baseline
      concentration of SP-LIR and beta E-LIR was seen in BAL of allergic subjects. In
      NAL of allergic subjects an increased baseline concentration of SP-LIR was found
      (beta E-LIR not detectable). After allergen provocation there was a rise of SP
      LIR and beta E-LIR in BAL fluids of allergic subjects immediately after
      provocation. In NAL fluids of allergic subjects allergen challenge resulted in a
      rise of SP-LIR within 10 minutes. Allergen provocation did not influence SP-LIR
      and beta E-LIR concentration in BAL and NAL in nonallergic controls. The
      demonstrated higher baseline levels of SP-LIR and beta E-LIR as well as the
      increase after provocation in the BAL and NAL of allergic subjects but not in
      nonallergic controls support the hypothesis that these neuropeptides contribute
      to allergic reactions in airways of humans.

PMID- 1383308
TI  - The relationship between late asthmatic responses and antigen-specific
      immunoglobulin.
AB  - The aim of this study was to examine the relationships between allergen-induced
      early and late airway responses and antigen-specific IgE, IgG, and lymphocyte
      subsets in blood and bronchoalveolar lavage (BAL). Brown Norway rats were
      sensitized at 7 weeks of age with ovalbumin (1 mg s.c.) with use of Bordetella
      pertussis as an adjuvant. Three weeks after sensitization, animals were
      anesthetized and challenged with an aerosol of ovalbumin (5% wt/vol in saline)
      for 5 minutes. Each animal was studied for 8 hours with repeated measurements of
      lung resistance. Blood was obtained at 0, 1, 2, and 3 weeks before ovalbumin
      challenge. Ovalbumin-specific IgE and IgG were determined by ELISA. No specific
      antibody was detectable before sensitization. Ovalbumin-specific IgE and IgG rose
      between 1 to 2 weeks after sensitization and peaked at 3 weeks. The IgE level did
      not correlate with the magnitude of either the early or the late responses. In a
      similar manner no correlation existed between the magnitude of specific IgG and
      the late response. However, a significant inverse correlation (r = -0.73; p <
      0.01) occurred between specific IgG and the early response. No correlation
      occurred between the ratio of helper (W3/25 +) to suppressor (OX-8 +) lymphocytes
      in blood and BAL and airway responses to allergen. The size of the early and late
      responses were correlated, suggesting a common stimulus. Despite the blunting of
      the early response by repeated sensitization the late response was unaffected,
      suggesting that the factors that determine the physiologic expression of the
      early and late responses are different.

PMID- 1383309
TI  - Effects of amiloride and furosemide on histamine release from human leukocytes
      induced by anti-IgE antibody.

PMID- 1383310
TI  - The antiallergic effects of antihistamines (H1-receptor antagonists).
AB  - Most first-generation and second-generation H1-receptor antagonists have readily
      demonstrable antiallergic effects in vitro, although high concentrations of some
      of the medications are required to inhibit mediator secretion from mast cells or
      basophils. These antiallergic effects can also be seen in vivo in skin, nasal,
      lung, and ocular challenge studies. Some H1-receptor antagonists appear to have
      an antiallergic effect in one organ but not in another. In many in vivo studies,
      doses of H1-receptor antagonists three or more times higher than those required
      for H1 blockade must be given to achieve the antiallergic effect. It would be
      premature to attempt to reclassify the H1 antagonists according to their
      antiallergic properties because these properties have not been investigated fully
      and their relative contribution to the overall therapeutic effectiveness of each
      H1 receptor antagonist is unknown.

PMID- 1383311
TI  - Antiallergic properties of the second-generation H1 antihistamines during the
      early and late reactions to antigen.
AB  - Some of the second-generation H1 antihistamines reduce the bronchoconstrictor
      response after exercise and antigen challenge. For example, terfenadine causes a
      slight but significant increase in forced expiratory volume after 1 second. At
      doses of 120 and 240 mg, terfenadine has a protective effect against asthma
      induced by ultrasonic nebulized distilled water and cold air hyperventilation
      challenge. Certain other newer antihistamines, such as ketotifen, azelastine, and
      cetirizine, have additional antiallergy properties. These effects include
      inhibition of eosinophil, basophil, and neutrophil migration and platelet
      activating factor-induced eosinophil accumulation in skin. The ability of
      cetirizine (and perhaps other antihistamines) to inhibit these responses at usual
      therapeutic doses may be useful in investigating the late allergic reaction.

PMID- 1383313
TI  - [Cytokines and pregnancy: physiology].
AB  - Several biological systems originating in the fetus and in the mother are
      involved in embryo implantation, maintenance of the pregnancy, protection of the
      fetus against outside influences and the start of labour (these are the immune
      system, endocrine system, and the endothelial system). In order to work
      efficiently there has to be some co-ordination. Cytokines which were first
      described by immunologists make it possible for information between the systems
      to be exchanged. The authors, referring to recent publications, show that there
      are several cytokines with specific receptors at the feto-placental interface.
      The place and the physiological role of these molecules in co-ordinating the
      links are discussed. These cytokines can be involved in many pathological
      situations.

PMID- 1383312
TI  - Relative sensitivity of Daphnia magna and Brachionus calyciflorus to five
      pesticides.
AB  - Comparative toxicity of several pesticides, lindane, endosulfan,
      pentachlorophenol (PCP),3,4-dichloroaniline (DCA) and copper sulphate has been
      tested to determine their lethality in two species of freshwater invertebrates,
      Daphnia magna and Brachionus calyciflorus. D. magna was more sensitive than B.
      calyciflorus to all the toxicants tested except to copper sulphate. DCA was the
      most toxic compound to D. magna and was followed in order of decreasing toxicity
      by copper sulphate, PCP, endosulfan and lindane. Copper sulphate was the most
      toxic chemical tested to the rotifer B. calyciflorus and was followed by PCP,
      endosulfan, lindane and DCA. The 24 hr LC50 values (mg/L) for D. magna and B.
      calyciflorus, respectively, were: lindane, 1.64 and 22.5; endosulfan, 0.62 and
      5.15; DCA, 0.20 and 61.5; PCP, 0.39 and 2.16; copper sulphate, 0.38 and 0.076.

PMID- 1383314
TI  - Marked hyperlipasemia in diabetic ketoacidosis. A report of three cases.
AB  - We report three patients with diabetic ketoacidosis (DKA) who presented with
      striking elevations of serum lipase levels and less striking elevations of
      amylase and trypsinogen. All three had nausea and vomiting, but none had
      objective evidence of abdominal pain, and computed tomography scans of the
      pancreas were unremarkable. These cases suggest the association of asymptomatic
      enzyme elevations with DKA. We review the literature on this subject.

PMID- 1383315
TI  - Prorenin is present in plasma from nephrectomized rats: interfering sulphydryl
      enzyme.
AB  - OBJECTIVES: The aim was to demonstrate whether prorenin is present in plasma from
      24-h nephrectomized rats. Its existence and concentration is currently under
      debate. DESIGN: Determination of the 50% inhibition concentration (IC50) values
      for inhibition of plasma renin in intact and 24-h nephrectomized rats. The potent
      and specific rat renin inhibitor CH-732 was used. METHODS: Our previously
      published method for the determination of rat prorenin was used. It is
      characterized by removal of an interfering trypsin-formed angiotensin I
      immunoreactive material before the renin incubation step. RESULTS: The trypsin
      activated prorenin-like activity of 24-h nephrectomized plasma was due only to a
      minor degree to real prorenin as judged by CH-732 inhibition. The major part of
      the prorenin-like activity was due to a hitherto unknown sulphydryl enzyme, which
      could be blocked by N-ethylmaleimide. In normal plasma all prorenin was real
      prorenin. The plasma concentration of real prorenin in 24-h nephrectomized rats
      was approximately 10% of that in intact rats. CONCLUSION: Prorenin is definitely
      present in nephrectomized plasma, but in low concentrations. The data support the
      concept that the major part of plasma prorenin in intact rats originates from the
      kidneys. The previously published values for prorenin in intact rats were
      correct, whereas those in 24-h nephrectomized rats were too high. If N
      ethylmaleimide is added to our previously published method for rat prorenin, it
      overcomes the three known problems with prorenin determination in rat plasma:
      trypsin generation of angiotensin I immunoreactive material; trypsin destruction
      of angiotensinogen; and interference in trypsin-activated nephrectomized plasma
      of a sulphydryl enzyme, which generates an angiotensin-I-like material.

PMID- 1383316
TI  - Peripheral B cell maturation. I. Immature peripheral B cells in adults are heat
      stable antigenhi and exhibit unique signaling characteristics.
AB  - Whether recently generated peripheral B cells in adults are functionally
      equivalent to immature B cells in the neonatal spleen is unknown. We have
      identified a splenic B cell subpopulation in adults whose phenotypic and in vitro
      characteristics closely resemble those of neonatal B cells. These cells are
      defined by the cell surface phenotype heat-stable Aghi (HSAhi), and make up 10 to
      15% of the adult splenic B cell pool. HSAhi B cells in adults bear the immature
      phenotype B220lo sIgMhi, and are 50% sIgD+. Furthermore, after sublethal
      irradiation, the initial wave of newly generated splenic B cells in self
      reconstituting adults express a similar phenotype. In keeping with previous data
      on neonatal B cells, HSAhi cells from either normal or self-reconstituting mice
      are refractory to stimulation with anti-IgM antibodies, yet proliferate upon LPS
      stimulation, and generate primary antibody responses if given appropriate T cell
      help. In contrast to neonatal cells, HSAhi adult B cells are refractory to
      stimulation with PMA plus ionomycin. Together, these data suggest that peripheral
      HSAhi B cells in adults correspond to recently generated B cells, whose signaling
      characteristics are distinct from previously described B cell subsets.

PMID- 1383317
TI  - Differential regulatory effects of intercellular adhesion molecule-1 on
      costimulation by the CD28 counter-receptor B7.
AB  - Although ligation of the CD3/TCR complex initiates an activation signal in T
      cells, additional costimulatory signals generated during cell-to-cell
      interactions with APC transduced via ligation of CD11a/CD18 and CD28 by their
      specific counter-receptor intercellular adhesion molecule (ICAM)-1 and B7,
      respectively, are required for optimal T cell proliferation and cytokine
      synthesis. Using soluble IgC gamma 1 fusion proteins of these costimulatory
      counter-receptors, we have recently shown that unactivated resting CD4+ T cells
      and Ag-primed CD4+ T cells differ in their response to the costimulation by ICAM
      1 and B7. Preferential proliferative responses of resting T and Ag-primed T cells
      to ICAM-1 and B7, respectively, prompted us to speculate that ICAM-1-induced
      signals may regulate coupling of the CD28 signaling pathway. Furthermore, both B7
      and ICAM-1 are co-expressed on APC and thus, may co-regulate activation-driven
      maturation of T cells. In this study, we have examined regulatory effects of IgC
      gamma 1 fusion proteins of B7, ICAM-1, and ICAM-2 (a homologue of ICAM-1) on each
      other's costimulation. We first demonstrate that TCR-directed costimulation of
      resting CD4+ T cells with ICAM-1 (ICAM-1 priming) but not ICAM-2 induces
      increased responsiveness to B7. Priming of CD4+ T cells with ICAM-1 induced
      higher expression of both CD18 and CD28 than that with either B7 or ICAM-2. Cross
      linking of CD28 induced faster and significantly higher cytoplasmic free calcium
      mobilization response in ICAM-1-primed CD4+ T cells than in resting, B7-primed,
      or ICAM-2-primed CD4+ T cells. B7 synergized with ICAM-1 but not ICAM-2 to
      augment proliferative responses of not only resting CD4+ T cells but also those
      that had been primed with either ICAM. Unlike resting or ICAM-2-primed CD4+ T
      cells, ICAM-1-primed CD4+ T cells efficiently proliferated in response to the
      synergistic costimulation of B7 and ICAM-2. In contrast, both ICAM-1 and ICAM-2
      inhibit B7-driven proliferation of Ag-primed CD4+ T cells. Thus, B7 and ICAM-1
      exert contrasting regulatory effects on the proliferation of CD4+ T cells
      depending on their state of activation-induced maturation.

PMID- 1383318
TI  - A monoclonal antibody against a novel 20-kDa protein induces cell adhesion and
      cytoskeleton-dependent morphologic changes.
AB  - A new murine IgA mAb (JKT.M1), developed against Jurkat T cells chronically
      infected with HIV IIIB induces in vitro homotypic aggregation in several
      hemopoietic cell lines. The JKT.M1 Ag is expressed on a wide variety of cell
      types including human lymphocytes, monocytes, platelets, RBC, human umbilical
      vein endothelial cells, many T cell lines, myelomonocytic cell lines, and a
      primate kidney cell line. The JKT.M1 Ag shows differential expression on
      myelomonocytic cells; it is present on K562 and HL60 cell lines, which represent
      precursors of E and monocytes, respectively, but is not expressed on the surface
      of U937 and THP-1 cell lines, which appear to represent intermediate cell types
      of the monocytic cell lineage. However, the JKT.M1 Ag is expressed on mature
      peripheral blood monocytes and the MonoMac cell line. Immunoprecipitation from
      cell lysates (Jurkat, SupT1, PBMC, MonoMac) with the JKT.M1 mAb yields a 20-kDa
      Ag with few if any carbohydrate residues as determined by N-glycanase and
      neuraminidase treatments. The pI appears acidic by two-dimensional gel analysis,
      and the nonreduced form migrates more slowly than the reduced form when analyzed
      by SDS-PAGE suggesting the presence of intramolecular disulfide bridge(s). JKT.M1
      mAb-induced cell adhesion is shown to be divalent cation- and temperature
      dependent. The adhesion induced by JKT.M1 mAb is inhibited by 20 microM
      cytochalasin B and also by 2 mM 2-deoxyglucose plus 10 mM sodium azide suggesting
      that cytoskeletal changes and metabolic energy are required. Aggregation induced
      by JKT.M1 appears to be independent of CD43, CD44, and VLA4 (CD29/CD49d), mAb
      against which have also been shown to induce homotypic cell adhesion. Anti-CD18
      mAb have been shown to inhibit homotypic aggregation in other studies but failed
      to do so in the present study. Thus JKT.M1-induced adhesion also appears to be
      independent of CD18, the beta-chain of leukocyte integrins. However, like mAb
      against LFA-1, immobilized JKT.M1 stimulates a T cell line to undergo dramatic
      morphologic changes which could be enhanced by the addition of phorbol ester.
      These data suggest that the novel 20-kDa molecule recognized by the JKT.M1 mAb
      may trigger cell adhesion through a previously undescribed mechanism.

PMID- 1383319
TI  - Role of hapten-anchoring peptides in defining hapten-epitopes for MHC-restricted
      cytotoxic T cells. Cross-reactive TNP-determinants on different peptides.
AB  - Synthetic hapten-peptide conjugates selectively modify cell-bound MHC class I
      molecules in a haplotype-specific way. We investigated the contribution of the
      carrier peptides to the structural specificity of T cell-antigenic TNP epitopes,
      using different H-2Kb-binding TNP-peptides and a collection of TNP/Kb-specific
      CTL clones. Adjustment of peptide sequences to the proposed Kb-specific "motif"
      (octamers with F or Y and L in positions 5 and 8, respectively) enhanced Kb
      binding and antigenicity by many orders of magnitude. Moreover, several clones
      reacted to peptides, containing the "motif" and TNP-lysine in position 4 but were
      otherwise unrelated by sequence. TNP in other positions was not recognized by
      these cells, but other CTL reacted to TNP in position 7. This points to the
      positioning of hapten determinants within the MHC binding groove as a major role
      of the anchoring peptide. However, determination of the limiting amounts of TNP
      peptides that elicit antigenicity or inhibit other Kb-restricted CTL reactions
      revealed that TCR also recognize variations in the sequences of carrier peptides.
      This contribution is low for TNP in position 4 but high in position 7, indicating
      lysine in position 4 as a particularly dominant and cross-reactive hapten
      anchoring site in Kb-associated peptides. This implies that cell modification
      with lysine-reactive TNP reagents results in immunodominant, highly repetitive
      TNP epitopes, which may explain the strong antigenicity and the allergenic
      properties of TNP, as well as the restricted TCR repertoire directed against this
      hapten. Our data further recommend hapten peptides for general studies of TCR-Ag
      interactions because in contrast to pure protein Ag, hapten epitopes tolerate
      substantial structural variations in the MHC-anchoring peptide, and can be
      located by hapten-specific antibodies.

PMID- 1383320
TI  - Recombinant Escherichia coli express a defined, cytoplasmic epitope that is
      efficiently processed in macrophage phagolysosomes for class II MHC presentation
      to T lymphocytes.
AB  - Although the processing of soluble Ag for presentation to T cells has been
      extensively studied in vitro, similar studies of phagocytic Ag processing have
      been limited. We have developed an in vitro model system to study the ability of
      macrophages to process recombinant Escherichia coli strain HB101 with cytoplasmic
      or surface expression of the well characterized T cell epitope of hen egg
      lysozyme (HEL) 52-61. This epitope was expressed within full length HEL or within
      a fusion protein containing the HEL epitope. Phagocytosis of E. coli with
      cytoplasmic expression of HEL or the HEL fusion protein resulted in strong
      presentation of HEL(52-61) to T cells. Surface-conjugated HEL was processed with
      even greater efficiency. Processing required viable macrophages, was inhibited by
      cytochalasin D, and was achieved within 20 min of bacterial contact with the
      macrophages. Within this time span, phagosomes containing bacteria fused with
      lysosomes, and the bacteria were extensively degraded. Uptake of as few as four
      bacteria per macrophage produced an Ag-specific T cell response. We conclude that
      bacterial compartmentalization of the antigenic epitope (cytoplasmic vs surface)
      had some effect on its processing, but that phagocytic Ag processing organelles
      contain extensive capacity to degrade internalized bacteria and liberate
      intracellular Ag epitopes for recycling and presentation, consistent with a
      central role for phagolysosomes. Thus, future recombinant bacterial vaccines may
      be effectively designed with T cell epitopes expressed either on the surface or
      within the bacterial cytoplasm.

PMID- 1383322
TI  - Interactions of tumor necrosis factor with granulocyte-macrophage colony
      stimulating factor and other cytokines in the regulation of dendritic cell growth
      in vitro from early bipotent CD34+ progenitors in human bone marrow.
AB  - Colonies of CD1a+ HLA-DR+/DQ+ CD4+ cells with the functional and some of the
      structural attributes of Langerhans cells are observed in human bone marrow
      cultures in semi-solid media and are assumed to be the progeny of an early
      progenitor, the dendritic/Langerhans cell CFU (CFU-DL). The cytokine-regulated
      growth of these cells has been studied using a chemically defined serum-free
      system to culture both unfractionated and highly enriched bone marrow progenitor
      cell populations. Although unfractionated cell growth was optimal in serum
      replete cultures with PHA-stimulated leukocyte-conditioned medium (PHA-LCM)
      suboptimal proliferation of CFU-DL was observed in serum even in the absence of
      PHA-LCM. No colonies were observed under serum-free conditions when granulocyte
      macrophage CSF (GM-CSF), IL-3, granulocyte CSF (G-CSF), and macrophage CSF (M
      CSF) were present at levels optimal for granulocyte colony-forming unit (CFU-G)
      and macrophage colony-forming unit (CFU-M) growth. Addition of IL-1 alpha to
      these cytokines stimulated a small number of CFU-DL. However, in the presence of
      GM-CSF and IL-3, TNF-alpha or TNF-beta (5 U/ml) were both highly effective in
      promoting growth up to 82% of optimal and CFU-G growth was also enhanced at these
      concentrations. TNF was only active during the first 3 days of culture and higher
      concentrations of TNF-alpha but not TNF-beta were inhibitory for both CFU-DL and
      CFU-G. CD34+ cell-enriched populations were also enriched for both myeloid
      progenitors (CFU-G + CFU-M) and CFU-DL to 36- and 48-fold, respectively, and
      single cell cultures of CD34+ cells yielded single colonies containing both CD1a+
      dendritic cells and CD1a- macrophages. Thus dendritic/Langerhans progenitors in
      the bone marrow expresses CD34, have a capacity for both macrophage and dendritic
      cell differentiation, and depend on hemopoietic growth factors and TNF for their
      further development in vitro.

PMID- 1383321
TI  - Activation of human basophils through the IL-8 receptor.
AB  - IL-8 and its structural analogs derived from blood platelets have been proposed
      as stimuli of IgE-independent basophil activation. In order to clarify the
      mechanism of action of these peptides, we examined the effects of pure IL-8,
      connective tissue-activating peptide III (CTAP-III), neutrophil-activating
      peptide 2 (NAP-2), and platelet factor 4 (PF-4) on blood basophils with and
      without pretreatment by IL-3, which modulates mediator release. After
      pretreatment with IL-3, significant histamine release was observed with 10(-8) M
      and 10(-7) M IL-8 and 10(-7) M NAP-2, but not with the other peptides. At higher
      concentrations (10(-6) M), however, all IL-8 analogs, as well as the unrelated
      cationic peptides poly-D-lysine, histone VS, and lysozyme, induced histamine
      release to variable degrees. Binding and competition studies with [125I]IL-8
      revealed specific IL-8R on basophils from a patient with chronic myelogenous
      leukemia and normal individuals. From 3500 to 9600 receptors with a mean Kd value
      of 0.15 nM were found on average per chronic myelogenous leukemia and normal
      basophil, respectively. NAP-2 weakly competed for IL-8 binding. IL-8 and, to a
      lesser extent, NAP-2 led to a transient rise of cytosolic free calcium
      concentration ([Ca2+]i), which was independent of a preexposure to IL-3. IL-8
      prevented the [Ca2+]i rise induced by NAP-2, but did not influence [Ca2+]i
      responses to other agonists, e.g. C5a, C3a, or platelet-activating factor. IL-8
      induced [Ca2+]i changes and histamine release in IL-3-primed basophils were
      pertussis toxin sensitive. CTAP-III or PF-4 did not compete for IL-8 binding, did
      not induce [Ca2+]i changes, and did not influence the [Ca2+]i response to IL-8
      and NAP-2. This study shows that IL-8 and NAP-2 activate human basophils by a
      receptor-mediated mechanism similar to that operating in neutrophils. At high
      concentrations histamine release can also be induced by cationic peptides by a
      mechanism that does not involve the IL-8R, and probably depends on cationic
      interactions.

PMID- 1383323
TI  - The disaccharide L-alpha-D-heptose1-->7-L-alpha-D-heptose1-->of the inner core
      domain of Salmonella lipopolysaccharide is accessible to antibody and is the
      epitope of a broadly reactive monoclonal antibody.
AB  - We generated a panel of mAb containing at least one specificity against each of
      the known chemotypes of the Salmonella LPS core domain and used them to
      investigate the accessibility of core determinants in smooth LPS. Most of the mAb
      were reactive with at the most three chemotypes of the core as determined by
      enzyme immunoassay and failed to bind smooth LPS or any of the complete cores of
      E. coli. One mAb, MASC1-MM3 (MM3), reacted with six different Salmonella core
      chemotypes, the R2 core of Escherichia coli and a variety of smooth LPS. This mAb
      reacted equally well with live and heat-killed bacteria. It bound to 123 of 126
      clinical isolates of Salmonella and 11 of 73 E. coli strains in a dot-immunoblot
      assay. Typical ladder-like patterns of bands were observed after immunoblotting
      of this mAb against electrophoretically resolved smooth LPS from the five major
      serogroups of Salmonella species (A, B, C1, D1, and E). MM3 had no reactivity
      with BSA conjugates of O-Ag polysaccharides from the above serogroups confirming
      specificity for a core epitope. Polysaccharides derived from or synthetic
      saccharides representative of the various chemotypes of Salmonella LPS core were
      tested as competitive inhibitors of the binding of MM3 to LPS. The results led to
      a conclusion that MM3 recognizes the structure, L-alpha-D-Heptose1-->7-L-alpha-D
      Heptose1-->disaccharide present as a branch in the Ra, Rb1, Rb2, Rb3 and Rc but
      lacking in the Rd1, Rd2, and Re chemotypes of the Salmonella LPS core. This
      disaccharide seems free and accessible on the basis of the previously calculated
      conformations of the Salmonella (Ra) and E. coli complete cores (R1, R2, R3, R4,
      and K12). It therefore defines or contains an epitope within the inner core
      subdomain of Salmonella LPS that is accessible to antibody in long-chained LPS
      and in intact bacteria with complete LPS.

PMID- 1383324
TI  - Conserved T and B cell epitopes on the M protein of group A streptococci.
      Induction of bactericidal antibodies.
AB  - To identify conserved T and B cell epitopes on the M protein of group A beta
      hemolytic streptococci, overlapping synthetic peptides that span the conserved
      carboxyl-terminal segment of the M-5 protein were constructed and used to
      immunize a panel of H-2 congenic mice. Proliferative T cell epitopes were
      identified and, in many cases, mice immunized with these peptides produced high
      titer antibodies to the same peptides indicating that these proliferative
      epitopes could also stimulate Th cells. Peptide-specific T cells and antisera
      were tested for their reactivity with porcine myosin, tropomyosin, human heart
      myosin synthetic peptides, and extracts of human pericardial and atrial heart
      tissue. Although there was minimal response of M peptide-specific T cells to any
      of these Ag, certain M peptide-specific antisera reacted to immunoblotted porcine
      myosin and to an immunoblotted extract of human atrial heart tissue. However, two
      conserved peptides, LRRDLDASREAKKQVEKALE and KLTEKEKAELQAKLEAEAKA, stimulated
      peptide-specific antibodies in B10.BR and B10.D2 mice respectively, which reacted
      minimally if at all with human atrial heart tissue extract. Furthermore, antisera
      to the former peptide, in a bactericidal assay involving human monocytes, could
      mediate killing of streptococci (82% of bacteria). Although this level of killing
      is less than that produced by antisera to the highly polymorphic type-specific
      aminoterminus (up to 100% killing), it provides evidence that conserved epitopes
      can be the targets of bactericidal antibodies. These conserved epitopes may be
      useful in a vaccine because they also stimulate T cells, thus allowing
      development of immunologic memory and natural boosting of an immune response
      after natural exposure.

PMID- 1383325
TI  - Activated microglia mediate neuronal cell injury via a nitric oxide mechanism.
AB  - Activated microglial have been proposed to play a pathogenetic role in immune
      mediated neurodegenerative diseases. To test this hypothesis, purified murine
      neonatal microglial were cocultured with neuronal cells derived from fetal brain.
      Activation with IFN-gamma and LPS of these cocultures brought about a sharp
      decrease in uptake of gamma-amino butyric acid and a marked reduction in neuronal
      cell survival. These effects varied with the density of microglia, the
      concentrations of the activation signals (IFN-gamma and LPS), and the duration of
      coculture. Inasmuch as addition of NG-monomethyl-L-arginine blocked these
      effects, a L-arginine-dependent neurocytotoxic mechanism was implicated. Abundant
      nitrite, a metabolite of the free radical nitric oxide (NO) derived from L
      arginine, was detected in activated microglial/neuronal cell cocultures and in
      purified microglial cell cultures but not in purified astrocyte or neuronal cell
      cultures, suggesting that microglial were the principal source of the NO. These
      findings support the hypothesis that microglia are the source of a neurocytotoxic
      free radical, and shed light on an additional mechanism of immune-mediated brain
      injury.

PMID- 1383326
TI  - Neutrophil aggregation is beta 2-integrin- and L-selectin-dependent in blood and
      isolated cells.
AB  - Neutrophil aggregation in response to formyl peptide was analyzed in blood and
      isolated cells by fluorescence flow cytometry. The isolated leukocyte aggregates
      and the leukocytes in blood were identified with the vital nucleic acid stain LDS
      751. This method enabled us to discriminate nucleated cells from other blood
      cells and to detect granulocyte aggregates without isolation or E lysis. Cells
      isolated in the absence of endotoxin retained the characteristics of cells in
      blood and exhibited similar aggregation kinetics and dose-response to formyl
      peptide. We show that it is possible to analyze epitope expression in blood with
      homogeneous flow cytometric assays and that carefully isolated neutrophils retain
      the expression characteristics of those in blood. The expression of CD18 was at
      its lowest levels in unstimulated cells, while the rate of formyl peptide
      stimulated aggregation was most rapid in these cells. Aggregation in isolated
      cells as well as blood preceded an increase in receptor expression. After
      stimulation, L-selectin expression decreased in both blood and isolated cells
      over a time frame similar to disaggregation. The aggregation response in blood
      was blocked by pretreatment with antibody to CD18 over a concentration range
      consistent with the amount of antibody bound. Aggregation was also blocked in
      isolated cells and blood by antibodies DREG-200 and DREG-56 to L-selectin, but
      not by isotype controls or anti-LFA-1. The results are discussed in terms of the
      roles of adhesive receptor expression and recognition in neutrophil aggregation.
      The methods validated here permit linkage between isolated cells and in vivo
      studies.

PMID- 1383327
TI  - Steel factor-induced tyrosine phosphorylation in murine mast cells. Common
      elements with IL-3-induced signal transduction pathways.
AB  - The c-kit/W gene encodes a transmembrane protein tyrosine kinase, which is the
      receptor for Steel factor (SLF). SLF shares many general characteristics of
      hemopoietic growth factors, stimulating the survival, proliferation, and
      differentiation of stem and progenitor cells. We have investigated the tyrosine
      phosphorylation events that ensue after SLF binding to the c-kit protein using
      primary cultures of murine mast cells as a model system and have compared the
      effects of SLF and IL-3. Proteins that became phosphorylated on tyrosine after
      treatment of cells with SLF included c-kit itself, and major protein substrates
      designated p130, p122, p118, p115, p112, p100, p77, p55, p44, and p42. The
      majority of these proteins were cytosolic and maximally phosphorylated within 2
      min of growth factor treatment. Combinations of immunoprecipitation and
      immunoblotting with antibodies specific for proteins known to be associated with
      signaling pathways demonstrated that none of the major tyrosine-phosphorylated
      species correlated with phospholipase C-gamma 1, GTPase activating protein, or
      phosphatidylinositol 3' kinase. However, stimulation with SLF led to a modest
      increase in tyrosine phosphorylation of the 85-kDa subunit of the
      phosphatidylinositol 3' kinase and increased association with a 150-kDa
      phosphotyrosyl protein, likely to be c-kit. Two species that did correlate with
      known elements were the 44- and 42-kDa polypeptides, shown to be members of the
      mitogen-activated protein kinase family. A subset of these proteins (p130,
      p115/112, p100, p55, p44, p42) were also tyrosine-phosphorylated when cells were
      stimulated by IL-3. MonoQ ion-exchange chromatography and two dimensional gel
      analyses were used to demonstrate that at least the p55, p44, and p42 substrates
      were identical, as well as some more minor species of molecular weights 50, 38,
      and 36 kDa, thus indicating common pathways of signaling in hemopoietic cells.
      Whereas in the case of SLF the dose-response characteristics of the proliferative
      response and the induction of tyrosine phosphorylation were similar, in the case
      of IL-3, much lower concentrations were required for maximal proliferation than
      maximal tyrosine phosphorylation. These studies form the basis for further
      molecular characterization of common components of signal transduction pathways
      in hemopoietic cells.

PMID- 1383328
TI  - T cell differentiation antigens on lymphocytes in the human intestinal lamina
      propria.
AB  - Recently, T cell subpopulations presumably representing memory T lymphocytes have
      been described in vitro. Intestinal lamina propria T cells (LP-T) have
      characteristics resembling those of memory cells. We therefore investigated the
      expression of surface Ag associated with memory phenotype in vitro on lamina
      propria lymphocytes (LPL) and PBL and on the T cell subpopulations defined by the
      bright expression of CD45R0 by flow cytometric analysis of isolated cell
      populations. LPL had significantly increased percentages of CD45R0 and CD58
      positive cells compared with PBL. Whereas PBL showed bimodal expression profiles
      of CD45R0, CD58, and CD2, the vast majority of LPL was bright for these Ag.
      Expression of CD45RA was significantly reduced in both frequency and intensity in
      LPL, and LPL had significantly reduced percentages of CD11a/CD18 and CD29
      positive cells compared with PBL. The CD45R0 bright T cell subpopulations of both
      PBL and LPL were characterized by a lack of CD45RA. CD45R0 bright T cells from
      the peripheral blood (PB-T) were predominantly bright for CD2, CD58, CD29, and
      CD11a/CD18 whereas CD45R0 dim PB-T had bimodal expression profiles and CD45R0
      negative PB-T were dim or even negative for these Ag. CD45R0 bright LP-T were
      also bright for CD2 and CD58 but had significantly reduced surface densities of
      CD11a/CD18 and CD29 compared with CD45R0 bright PB-T. The surface density of CD29
      on CD45R0 bright LP-T corresponded to that of CD45R0 negative PB-T, and a
      significant proportion of CD45R0 bright LP-T was even negative for CD11a/CD18 and
      CD29. Additionally, CD45R0 bright LP-T in contrast to PB-T were characterized by
      a lack of 1-selectin and the expression of CDw49a and the mucosa-specific T cell
      Ag HML-1 on high percentages of cells. Our results show that the phenotype of
      CD45R0 bright T cells from the lamina propria clearly deviates from that of
      memory T cells in vitro and of CD45R0 bright T cells in the peripheral blood. We
      conclude that memory T cell populations in vivo undergo specific differentiation
      depending on their tissue localization, leading to unique phenotypic and
      presumably functional features.

PMID- 1383329
TI  - The CD19/CD21 signal transducing complex of human B lymphocytes includes the
      target of antiproliferative antibody-1 and Leu-13 molecules.
AB  - CD19 is a member of the Ig superfamily expressed on the surface of B lymphocytes
      that may be involved in the regulation of B cell function. Immunoprecipitation
      studies with B cell lines solubilized by digitonin have shown CD19 to be part of
      a multimolecular complex that includes CD21 (CR2) and other unidentified
      proteins. In this study, two of the CD19-associated proteins were identified as
      TAPA-1, which is expressed on most cell types, and Leu-13, which is expressed on
      subsets of lymphoid cells. TAPA-1 and Leu-13 are physically associated in many
      cell lineages. CD19 and CD21 mAb each specifically coprecipitated proteins of the
      same size as those precipitated by TAPA-1 and Leu-13 mAb from B cell lines and
      cDNA-transfected K562 cell lines. Western blot analysis with a TAPA-1 mAb
      verified the identity of TAPA-1 in CD19 and CD21 immunoprecipitated materials. In
      addition, when TAPA-1 or Leu-13 were crosslinked and patched on the cell surface,
      all of the CD19 comigrated with TAPA-1 and some of the CD19 comigrated with Leu
      13. Furthermore, mAb binding to CD19, CD21, TAPA-1, and Leu-13 on B cell lines
      induced similar biologic responses, including the induction of homotypic
      adhesion, inhibition of proliferation, and an augmentation of the increase in
      intracellular [Ca2+] induced by suboptimal cross-linking of surface Ig on B cell
      lines. Together, these data suggest that TAPA-1 and Leu-13 are broadly expressed
      members of a signal transduction complex in which lineage-specific proteins, such
      as CD19 and CD21, provide cell-specific functions.

PMID- 1383330
TI  - In vitro growth of bone marrow-resident T cell precursors supported by mast cell
      growth factor and IL-3.
AB  - The growth requirements of bone marrow-resident cells that are able to
      differentiate along the T cell lineage (pre-T cells) have not been well
      established. We recently have shown that the T cell-derived lymphokine IL-3 is
      able to maintain pre-T cells in vitro for at least 2 weeks. However, in our
      initial studies, we were not able to ascertain whether IL-3 induced pre-T cell
      growth during culture, or whether IL-3 simply maintained the viability of these
      progenitors. To address this issue, we used a multiple dose assay system to
      assess the level of pre-T cell activity (thymic repopulation) in a selected
      population of bone marrow cells (CD3-, Thy-1.2+) both before and after culture in
      IL-3. In addition, we tested the potential role of mast cell growth factor (MGF)
      in the growth and maintenance of pre-T cells in vitro. The results of these
      studies showed that IL-3 produced a modest, but consistent increase in the pre-T
      cell activity during culture. Culture of CD3-, Thy-1.2+ bone marrow cells in MGF
      also resulted in an increase in the total amount of detectable pre-T cell
      activity among the cultured cells. The most dramatic increases in pre-T cell
      activity, however, were induced by the culture of the selected marrow cells in
      both MGF and IL-3. Cultures supplemented with both cytokines produced net
      increases in pre-T cell activity of 40- to 75-fold after 10 days of culture.
      Because the increases in pre-T cell activity were not accompanied by observable
      increases in the size of thymic colonies produced by the pre-T cells, the
      increased levels of pre-T cell activity appeared to result from increases in pre
      T cell numbers during culture. Thus, in addition to the other activities ascribed
      to MGF, this cytokine displays pre-T cell growth factor activity and can
      synergize with IL-3 in that capacity. The use of MGF in conjunction with IL-3
      provides the best system described to date for the propagation of pre-T cells in
      primary bone marrow cell cultures.

PMID- 1383331
TI  - Functional analysis of DR17(DR3)-restricted mycobacterial T cell epitopes reveals
      DR17-binding motif and enables the design of allele-specific competitor peptides.
AB  - We have previously shown that p3-13 (KTIAY-DEEARR) of the 65-kDa heat shock
      protein (hsp65) of Mycobacterium tuberculosis and Mycobacterium leprae is
      selected as an important T cell epitope in HLA-DR17+ individuals, by selectively
      binding to (a pocket in) DR17 molecules, the major subset of the DR3 specificity.
      We have now further studied the interaction between p3-13, HLA-DR17 and four
      different TCR (V beta 5.1, V beta 1, and V beta 4) by using T cell stimulation
      assays, direct peptide-DR binding assays, and a large panel (n = 240) of single
      amino acid substitution analogs of p3-13. We find that residues 5(I) and 8(D) of
      p3-13 are important DR17 binding residues, whereas the residues that interact
      with the TCR vary slightly for each DR17-restricted clone. By using N- and C
      terminal truncated derivatives of p2-20 we defined the minimal peptide length for
      both HLA-DR17 binding and T cell activation: the minimal peptide that bound to
      DR17 was seven amino acids long whereas the minimal peptide that activated T cell
      proliferation was eight amino acids in length. Furthermore, two new DR17
      restricted epitopes were identified on hsp70 and hsp18 of M. leprae. Alignment of
      the critical DR17-binding residues 5(I) and 8(D) of p3-13 with these two novel
      epitopes and two other DR17-binding peptides revealed the presence of highly
      conserved amino acids at positions n and n + 3 with I, L, and V at position n and
      D and E at position n + 3. D and E are particularly likely to interact with the
      DR17-specific, positively charged pocket that we have defined earlier. Based on
      these results, a set of single amino acid substituted analogs that failed to
      activate these T cell clones but still bound specifically to DR17 was defined and
      tested for their ability to inhibit T cell activation by p3-13 or other DR17
      restricted epitopes. Those peptides were able to inhibit the response to p3-13 as
      well as other DR17-restricted mycobacterial epitopes in an allele-specific
      manner, and are anticipated to be of potential use for immunotherapeutic and
      vaccine design strategies.

PMID- 1383332
TI  - Mapping of epitopes, glycosylation sites, and complement regulatory domains in
      human decay accelerating factor.
AB  - Decay accelerating factor (DAF, CD55) is a glycophospholipid-anchored membrane
      protein that protects cells from complement-mediated damage by inhibiting the
      formation and accelerating the decay of C3/C5 convertases. DAF deletion mutants
      lacking each of the four short consensus repeats (SCR) or the serine/threonine
      rich region (S/T) were created by site-directed mutagenesis. These deletion
      mutants were expressed by stable transfection in Chinese hamster ovary cells for
      the purpose of mapping important structural and functional sites in DAF. The
      epitopes on DAF for 16 murine mAb were mapped by immunoprecipitation studies as
      follows: SCR1, 6; SCR2, 3; SCR3, 3; SCR4, 3; S/T, 1. Testing of 13 mAb showed
      complete blocking of DAF function only by 1C6 and 1H4, both directed at SCR3. The
      single N-linked glycosylation site was confirmed at a location between SCR1 and
      SCR2, and the multiple O-linked oligosaccharides were localized to the S/T
      region. Functional activity of DAF mutants was assessed by the ability of these
      transfected constructs to protect Chinese hamster ovary cells from cytotoxicity
      induced by rabbit antibody plus human complement. Removal of SCR1 had no effect
      on DAF function, but individual deletion of SCR2, SCR3, or SCR4 totally abolished
      DAF function. Surprisingly, deletion of the S/T region totally abrogated DAF
      function, but this could be restored by a fusion construct placing the four SCR
      domains of DAF onto the HLA-B44 molecule, implying that the O-glycosylated S/T
      region serves as an important but nonspecific spacer projecting the DAF
      functional domains above the plasma membrane. Overall, the creation of DAF
      deletion mutants has elucidated important structure-function relations in the DAF
      molecule.

PMID- 1383333
TI  - Effects of tumor necrosis factor, lipopolysaccharide, and IL-4 on the expression
      of vascular cell adhesion molecule-1 in vivo. Correlation with CD3+ T cell
      infiltration.
AB  - We have injected human TNF, LPS, and IL-4 into the skin of baboons to examine
      regulation of endothelial leukocyte adhesion molecules (ELAM) in vivo and to
      determine which endothelial adhesion molecules correlate temporally and spatially
      with cytokine-induced T cell infiltration. The expression of adhesion molecules
      ELAM-1 (E-selectin), VCAM-1, and ICAM-1 (CD54) were quantified by
      immunocytochemical staining of frozen sections obtained from skin biopsies; T
      cell infiltration was measured by immunocytochemical staining of CD3+ T cells in
      serial sections. We found that injection of TNF causes late (24 to 48 h) T cell
      infiltration whereas injection of LPS, in doses that do not cause tissue
      necrosis, does not. The ability of TNF (but not LPS) to recruit T cells
      correlates with the ability of TNF to cause sustained endothelial cell adhesion
      molecule expression. Expression of VCAM-1 on post-capillary venules showed the
      highest degree of spatial localization with infiltrates. IL-4, although not
      proinflammatory by itself, can cause T cell infiltration in combination with an
      ineffective dose of TNF. The ability of IL-4 to augment TNF-induced inflammation
      best correlates with the ability of the combination of IL-4 and TNF to increase
      endothelial VCAM-1 expression. In contrast, IL-4 does not promote T cell
      infiltration or endothelial VCAM-1 expression in combination with LPS. In
      cytokine-injected tissues, VCAM-1 is also expressed on connective tissue cells
      other than endothelium, including smooth muscle and perineural cells, where it is
      induced by cytokines in parallel with endothelial VCAM-1. Overall, our data
      support the hypothesis that endothelial VCAM-1 expression contributes to T cell
      extravasation at sites of inflammation. Furthermore, we find that IL-4, a product
      a Ag-activated T cells, can interact with TNF to selectively promote VCAM-1
      expression and the development of T cell-rich infiltrates, characteristic of Ag
      induced inflammatory reactions.

PMID- 1383334
TI  - Regulation of IL-2 receptor subunit genes in human monocytes. Differential
      effects of IL-2 and IFN-gamma.
AB  - We investigated the effects of IFN-gamma and IL-2 on IL-2R alpha and beta mRNA
      expression in human monocytes. Low basal expression of IL-2R beta mRNA was
      detected in fresh monocytes. Stimulation of monocytes with IL-2 induced a
      significant increase of IL-2R beta mRNA, but did not induce IL-2R alpha mRNA. In
      contrast, stimulation of monocytes with IFN-gamma-induced IL-2R alpha mRNA, but
      did not modify IL-2R beta mRNA. Five U/ml of IFN-gamma induced IL-2R alpha mRNA
      and 2.2 nM of IL-2 induced IL-2R beta mRNA, both within 3 h. Nuclear run-on
      experiments demonstrated that the induction of IL-2R alpha mRNA by IFN-gamma is
      controlled, at least in part, at the transcriptional level. In contrast, the
      enhancement of IL-2R beta mRNA by IL-2 is controlled at a posttranscriptional
      level and is associated with an increase in the half-life of IL-2R beta mRNA. The
      results of studies on the cytotoxic activity and on the expression of c-fms mRNA
      of monocytes activated by the combination of IFN-gamma and IL-2 show that
      pretreatment with IFN-gamma renders monocytes more sensitive to activation by IL
      2. These results demonstrate that the IL-2R alpha and IL-2R beta subunits are
      induced by different lymphokines through distinct mechanisms and that both
      receptor subunits can influence the response of monocytes to IL-2.

PMID- 1383335
TI  - The supportive effects of IL-7 on eosinophil progenitors from human bone marrow
      cells can be blocked by anti-IL-5.
AB  - Human rIL-7 was studied for its effects on myeloid and erythroid progenitors from
      human bone marrow cells. IL-7 did not support the granulocytic/monocytic or
      erythroid lineage but exclusively stimulated eosinophil colony formation (CFU-Eo)
      (4 +/- 3 vs 48 +/- 17 CFU-Eo/10(5) nonadherent fraction-non-T cell (NAF-NT)
      cells). This supportive effect was not mediated by T cells or monocytes because
      similar results were obtained with or without T cell or adherent depleted cell
      fractions. In addition, it was shown that CD34+ sorted cells could be stimulated
      by IL-7 (0 vs 15 +/- 9 CFU-Eo/3 x 10(3) CD34+ cells) Furthermore studies with IL
      3 or granulocyte-macrophage CSF (GM-CSF) demonstrated an additive effect on the
      IL-7 supported colony formation. Finally, experiments were performed with anti-IL
      3, anti-GM-CSF, anti-IL-1, and anti-IL-5 to exclude the possibility that IL-7
      indirectly stimulated the eosinophil progenitor cell. Anti-GM-CSF, anti-IL-1, or
      anti-IL-3 did not influence the supportive effects of IL-7. However, anti-IL-5
      did abolish the effects of IL-7 on the eosinophil colony formation (69 +/- 15 vs
      3 +/- 2 CFU-Eo/10(5) NAF-NT, n = 3). Similar results were obtained with CD34+
      sorted cells. Moreover, IL-5 mRNA expression could be demonstrated in IL-7
      stimulated NAF-NT cells. These data suggest that the supportive effects of IL-7
      on eosinophil precursors are mediated by the endogenous release of IL-5.

PMID- 1383336
TI  - Inhibition of macrophage protein kinase C-mediated protein phosphorylation by
      Leishmania donovani lipophosphoglycan.
AB  - The cell surface lipophosphoglycan (LPG) from Leishmania donovani promastigotes
      is a potent inhibitor of purified protein kinase C (PKC) activity in vitro. In
      this study, we have investigated the effect of LPG on the activation process of
      PKC in murine bone marrow-derived macrophages. The extent and kinetics of calcium
      ionophore A23187-induced [3H] phorbol dibutyrate binding to macrophages were not
      affected by LPG pretreatment or infection with either wild-type or LPG-deficient
      promastigotes, indicating no effect on the association of calcium-dependent PKC
      with the plasma membrane. In contrast, LPG inhibited the phosphorylation of both
      the PKC-specific VRKRTRLLR substrate peptide and MARCKS, and endogenous PKC
      substrate, in 1-oleoyl-2-acetyl-glycerol-stimulated macrophages. These
      observations provide direct evidence that LPG effectively inhibits PKC activity
      in intact macrophages. Finally, depletion of PKC rendered macrophages more
      permissive for the proliferation of L. donovani, suggesting that inhibition of
      PKC-dependent events contributes to the survival of this parasite within its host
      cell.

PMID- 1383337
TI  - Evidence for early onset, polyclonal activation of T cell subsets in mice
      homozygous for lpr.
AB  - Mice homozygous for lpr and gld develop profound lymphadenopathy characterized by
      the accumulation of two functionally anergic T cell subsets, a predominant
      B220+CD4-CD8- double negative (DN) population and a minor, closely related CD4
      dull+ B220+ population. Lymph nodes from diseased lpr and gld mice also contain
      abnormally high numbers of conventional T cells, and we reported recently that a
      high proportion of lpr and gld CD4+B220- T cells have the hallmarks of primed or
      memory T cells. In the present study, we further investigated the extent,
      ontogeny, and possible causes of T cell activation in lpr and gld mice. The
      criteria used to identify primed or memory T cells included activation-dependent
      increases in the expression of CD44, LFA-1, and the early activation Ag, CD69,
      and decreases in the expression of Mel-14 and CD45RB, as well as quantitative
      differences in the in vitro production of IFN-gamma and the TNF-alpha by
      stimulated cells. A comparison of TCR V beta gene utilization by lpr T cell
      subsets also was undertaken. The results showed that T cell activation was
      widespread and complex. CD8+ T cells exhibited a similar pattern of activation to
      CD4+B220- T cells. The activation of these two subsets occurred in parallel, was
      in evidence by 4 to 6 wk of age, and was both chronic and progressive. The
      proportions of CD44hiLFA-1hi, CD4+B220-, and CD8+ T cells increased steadily
      between 4 and 20 wk of age, but changes in T cell growth, Mel-14, and CD45RB
      expression and cytokine secretion were not observed until mice were older than 11
      wk. A very different pattern of activation was observed for B220+ T cells. At all
      ages, B220+ DN and CD4+B220+ T cells were CD44hiMel-14hi and 60 to 75% were
      CD69+. The expression of CD69 appeared to be stimulus dependent rather than
      constitutive, suggesting that these cells, too, may be chronically stimulated in
      vivo. In keeping with their anergic state, DN T cells responded poorly to cross
      linking of CD69. The stimuli inducing chronic activation of CD4+B220- and CD8+ T
      cells are unlikely to include inappropriate reactions to autoantigens because
      there was no evidence for selective accumulation of CD4+ or CD8+ T cells bearing
      particular V beta genes or potentially self-reactive cells that normally are
      deleted in the thymus. By comparison, C3H-lpr DN cells displayed some potentially
      significant differences in V beta 6 and V beta 9 expression from CD4+B220- and
      CD8+ T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1383338
TI  - Detection of a vigorous HIV-1-specific cytotoxic T lymphocyte response in
      cerebrospinal fluid from infected persons with AIDS dementia complex.
AB  - AIDS dementia complex is a common neurologic disorder in later stages of HIV-1
      infection. Because virus-specific CTL have been shown to contribute to neurologic
      disease in certain viral illnesses, we examined the cerebrospinal fluid of HIV-1
      infected persons with various stages of AIDS dementia complex for the presence of
      HIV-1-specific CTL. In five of six subjects studied, HIV-1-specific CTL were
      identified in the cerebrospinal fluid. These CTL were directed at epitopes within
      the gag, reverse transcriptase, envelope, and nef proteins and restricted by HLA
      class I Ag. In four of these subjects, virus-specific CTL were detected in higher
      numbers in the cerebrospinal fluid compared to the peripheral blood, suggesting a
      specific recruitment to or local induction within the nervous system. These
      studies demonstrate the presence of a vigorous and broadly directed CTL response
      to HIV-1 in the central nervous system of infected persons with AIDS dementia
      complex, and provide immunologic evidence of localized intrathecal infection.
      Although HIV-1-specific CTL may serve to inhibit viral replication in the central
      nervous system, the presence of a persistent CTL response in the central nervous
      system may also contribute to the neurologic disorders characteristic of HIV-1
      infection.

PMID- 1383339
TI  - Heterogeneity in the recognition of the simian immunodeficiency virus envelope
      glycoprotein by CD4+ T cell clones from immunized macaques.
AB  - CD4+ T cell recognition of the simian immunodeficiency virus (SIV) surface
      envelope (env) glycoprotein was examined by using a panel of 10 T cell lines and
      4 T cell clones derived from 10 individual macaques immunized with inactivated
      SIV or recombinant SIV env proteins. The results demonstrated that CD4+ T cells
      from each animal recognized between 1 and 7 peptides in 4 distinct regions of the
      protein including both variable and conserved domains. MLR of PBMC from selected
      macaques together with RFLP analysis by using the HLA DR beta probes suggested
      that animals of distinct MHC class II haplotypes can recognize identical
      peptides. These T cell epitopes within conserved regions of the envelope protein,
      together with identified linear B cell epitopes recognized by neutralizing
      antibodies, may be relevant in vaccine design.

PMID- 1383340
TI  - Differential membrane labelling of human lymphocyte subsets by PKH-2 examined by
      multiparameter flow cytometry. A possible correlation between lipid composition
      of cellular membranes and functional properties?
AB  - Human peripheral blood lymphocytes were stained simultaneously with the
      lipophilic membrane label PKH-2 and surface markers and analysed by
      multiparameter flow cytometry. A biphasic staining distribution was observed for
      T (CD3+) as well as B (CD19+) cells. Within the T subset, CD4+ cells stained
      almost exclusively with bright PKH-2 intensity, while CD8+ cells exhibited a more
      pronounced bimodal staining pattern. No difference in staining intensity was
      noted for CD4+CD45R0+ vs. CD4+CD45R0- cells. This multiparameter staining method
      demonstrates differences in membrane lipid composition between different human
      lymphocyte subsets, and suggest that caution must be exercised when evaluating
      PKH-2 labelling of human lymphocytes.

PMID- 1383341
TI  - Enumeration of interleukin-1 alpha and beta producing cells by flow cytometry.
AB  - A technique for intracytoplasmic immunofluorescence staining to detect and
      quantify human interleukin-1 alpha (IL-1 alpha) and beta (IL-1 beta) in CD4, CD8,
      and CD14 positive lymphoid cells is described. Mononuclear cells stimulated in
      vitro with PHA to produce IL-1, were fixed and made permeable to antibodies by
      sequential exposure to paraformaldehyde and the detergent n-octyl-glucoside.
      Cytoplasmic and surface staining of both forms of IL-1 were demonstrated by
      indirect fluorescence using IL-1 beta and IL-1 alpha specific mouse monoclonal
      antibodies and quantified with flow cytometry.

PMID- 1383342
TI  - A new and simple method for studying the binding and ingestion steps in the
      phagocytosis of yeasts.
AB  - Autoclaved yeasts are stained light pink by May-Grunwald Giemsa (MGG). If treated
      with tannic acid solution just before MGG staining, they display a deep violet
      color. It seemed possible that these properties could be used to discriminate
      between extra- and intracellular yeasts in a phagocytosis test, extracellular
      yeasts being violet and intracellular yeasts being pink. To validate this
      protocol, quantitative studies of phagocytosis by MALU cells (a murine macrophage
      cell line) were performed in the presence or absence of drugs known to interfere
      with phagocytosis. After treatment of cells with cytochalasin B, the mean number
      of pink yeasts per cell decreased in a dose-dependent manner, the mean number of
      violet yeasts increased in a dose-dependent manner, whereas the total number of
      cell-associated yeasts remained almost unchanged whatever the dose used. After
      treatment with alpha-mannans or chloroquine, the mean numbers of both violet and
      pink yeasts decreased in a dose-dependent manner. These results confirmed that
      (i) violet yeasts are extracellular, (ii) autoclaved yeasts recognize lectin
      receptors, and (iii) unstained (pink) yeasts are intracellular. We show that this
      simple method can be used for quantitative light microscopic analysis of both the
      attachment and internalization steps in the phagocytosis of yeasts.

PMID- 1383343
TI  - In vitro measurement and screening of monoclonal antibody affinity using
      fluorescence photobleaching.
AB  - Antibody screening is a routine in vitro assay in monoclonal antibody development
      and production. We have recently adapted the fluorescence photobleaching method
      to quantify antibody mass transport and binding parameters in bulk solution
      (Kaufman and Jain, 1990, 1991). The present study uses this in vitro method to
      screen a series of monoclonal antibodies (IgG) developed against the rabbit VX2
      carcinoma tumor line. These experiments indicate that the three antibodies
      recognize distinct epitopes on the tumor, with equilibrium binding constants of
      1.3 +/- 0.5, 5.1 +/- 3.6 and 2.0 +/- 1.1 x 10(7) M-1 for the antibodies RVC-184,
      RVC-626 and RVC-779, respectively. The antibody diffusion coefficient revealed no
      dependent upon protein concentration or antigen bead volume fraction within the
      ranges investigated. It was demonstrated experimentally that the interactions
      conformed to a reaction limited binding model of fluorescence recovery, that the
      system was at equilibrium, and that non-specific binding due to the fluorescein
      probe was not significant. Once the non-reactive fraction of antibody is
      determined, this photobleaching technique does not require perturbation or
      physical separation of the unbound species. As such, it has many potential
      applications including in vivo investigation of binding parameters.

PMID- 1383344
TI  - Rapid attachment of a helper T cell epitope to branched peptides by fragment
      condensation to give enhanced immunogenicity.
AB  - We describe a rapid method of fragment condensation to couple a helper T cell
      epitope, active in BALB/c mice, to the amino terminus of branched peptides (or
      'multiple antigenic peptides', MAPs). The helper T cell epitope-MAP conjugate
      considerably enhanced the immunogenicity in BALB/c mice of branched peptides. The
      method of fragment condensation, whereby the helper T cell epitope portion of the
      immunogen is added as a 'cassette' in a one step addition process, is both faster
      and more convenient than continuous step-by-step addition of individual amino
      acids and is likely to be generally applicable. The method should be advantageous
      in the development of peptide based vaccines.

PMID- 1383345
TI  - Stimulation of human T cells by sparse antigens captured on immunomagnetic
      particles.
AB  - The acetylcholine receptor (AChR) of muscle is the target of the pathogenic
      antibodies in the human autoimmune disease myasthenia gravis (MG). For studies on
      the autoreactive T cells presumed to be responsible, use of intact human
      autoantigen would be optimal, but it was thought to be prohibitively scarce.
      However, adsorption to the surface of immunomagnetic particles (Dynabeads) of
      intact AChR from whole muscle extracts or from affinity-purified preparations,
      using mouse anti-human AChR Mabs, largely overcomes this problem. Together with
      antigen presenting cells (APC), this bead-bound AChR has consistently and
      maximally stimulated an established MG T cell line (previously selected with
      recombinant human AChR alpha subunit) that recognises the 144-156 region of the
      human alpha sequence (Ong et al., 1991). For equivalent T cell stimulation, bead
      bound AChR was at least 10(3) times more potent than soluble AChR or recombinant
      alpha subunit, and 10(6) times more potent than peptide 144-156, implying that
      antigen in this form is targetted very efficiently to APC and thus to T cells.
      Finally, we have obtained similar results with T cells specific for other
      antigens suggesting that this method may have wider applications.

PMID- 1383346
TI  - Use of anti-peptide antibodies for the design of antigen-specific immune complex
      assays.
AB  - A simple and sensitive method is described for the detection of circulating
      immune complexes (ICs) in an antigen-specific manner. The method is based on the
      use of anti-peptide antibodies as solid-phase capture reagents to bind antigen
      which is complexed to serum antibodies. The bound serum antibody is detected with
      a labelled second antibody. The method requires that the anti-peptide antibodies
      bind native protein efficiently, and that the anti-peptide antibodies do not
      compete with antibodies raised against the native protein which are involved in
      IC formation. Two anti-peptide antibodies specific for the hepatitis B surface
      antigen (HBsAg) and the hepatitis B e antigen (HBeAg), which possessed the
      requisite characteristics, were chosen as models for IC assay development. The
      solid-phase, anti-peptide based assays efficiently detected HBsAg and HBeAg
      containing ICs in preformed antigen/antibody mixtures and in the serum of
      chronically infected hepatitis B patients.

PMID- 1383347
TI  - Molecular cloning of murine monoclonal anti-idiotypic Fab.
AB  - Anti-idiotypic antibodies (Ab2) binding to idiotopes on antibodies with various
      antigen binding specificities (Ab1) are potential regulators of immunity in a
      variety of diseases, such as autoimmunity, cancer, and viral, bacterial, or
      parasitic infections. Furthermore, Ab2 are useful probes for the characterization
      of receptor/ligand interactions. Thus far, Ab2 production has been limited to the
      isolation of polyclonal Ab2 from immune sera or monoclonal Ab2 from hybridoma
      supernatants. However, both approaches have produced a limited number of Ab2. As
      an alternative approach, we demonstrate here the production of Ab2-Fab by using
      repertoire cloning. Using HIV-1 as a model system, the Ab2-Fab were generated
      from the spleens of mice immunized with the virus-neutralizing and syncytia
      inhibiting anti-HIV-1 monoclonal antibody 0.5 beta. A bacteriophage lambda vector
      system was used to express a combinatorial library in Escherichia coli. Iodinated
      0.5 beta was used to identify 17 Ab2-Fab clones. DNA sequence analysis of five
      clones revealed three similar kappa and Fd combinations. The Ab2-Fab bound with
      high affinity (3.5-6.5 x 10(9) liters/mol) specifically to the Ab1 and not to
      isotype-matched antibodies with unrelated specificities. The three Ab2-Fab
      probably bind to the same idiotope on the Ab1 as demonstrated in cross
      competition binding studies. The Ab2-Fab inhibited binding of the Ab1 to antigen,
      and therefore, may functionally mimic the epitope defined by the Ab1. Repertoire
      cloning of Ab2-Fab may facilitate the generation of Ab2 that have potential as
      modulators of immune responses against various antigens.

PMID- 1383348
TI  - T helper epitopes enhance the cytotoxic response of mice immunized with MHC class
      I-restricted malaria peptides.
AB  - We have previously derived MHC class I (H-2Kd) restricted cytotoxic T lymphocytes
      (CTL) from BALB/c mice immunized with irradiated sporozoites from Plasmodium (P.)
      berghei and P. yoelii. The CTL recognize synthetic peptides corresponding to a
      region of the circumsporozoite (CS) protein that is homologous in the two
      species. In the present study, we have attempted to induce CS-specific CTL by
      immunization with those peptides in incomplete Freund's adjuvant. Only a low
      level CTL response was detected in BALB/c mice immunized with synthetic peptides
      corresponding to the Pb or Py CTL epitopes. In contrast, CS-specific CTL
      responses could be readily detected in mice injected with mixtures of peptides
      that combined the P. berghei or P. yoelii CTL epitopes with previously defined T
      helper epitopes. Several different T helper epitopes were shown to enhance the
      response when injected as separate peptides in a mixture, or when covalently
      linked to a CTL epitope. These results may have general implications for the
      elicitation of CTL responses to defined CTL epitopes and for the design of
      peptide-based synthetic vaccines.

PMID- 1383349
TI  - Low-energy helium neon laser irradiation does not alter human keratinocyte
      differentiation.
AB  - There are reports that low-energy HeNe irradiation can enhance wound healing in
      vivo. We have previously demonstrated that HeNe irradiation increases the
      motility of human epidermally derived keratinocytes in vitro. Here we investigate
      whether HeNe irradiation alters normal keratinocyte differentiation, which is
      essential for the formation of a normal, functioning epidermis. Subconfluent
      keratinocyte cultures were irradiated three times within 24 h with either 0, 0.8,
      3, or 7.2 J/cm2. After cultures reached post-confluence, parameters of growth and
      differentiation, such as cell number, cornified envelope (CE) formation, and
      transglutaminase activity were measured. No significant differences were found
      between the control (0 J) and irradiated cultures in these assays. We also
      examined the pattern of newly synthesized keratins in cultures irradiated with
      7.2 J/cm2 three times within a 24-h period. Both control and irradiated cultures
      exhibited similar keratin patterns. These results provide evidence that HeNe
      irradiations of up to 7.2 J/cm2 have no direct deleterious effect on normal
      keratinocyte differentiation needed for the formation of a functional epidermis.
      Hence, it is anticipated that the clinical use of the HeNe laser irradiance that
      enhances keratinocyte migration in vitro (0.8 J/cm2) to promote wound healing in
      vivo will not alter the ultimate integrity or differentiated function of the
      epidermis that migrates to cover the wounded area.

PMID- 1383350
TI  - Growth characteristics and differentiation of basal cell carcinoma in vitro-
      immunohistochemical, gel electrophoretic, and ultrastructural analysis.
AB  - Cell cultures were established from 48 solid basal cell carcinomas (BCC) and from
      the normal epidermis of the same patients. The growth characteristics and
      differentiation of BCC cells in vitro were compared with normal keratinocytes
      (nKC) by using immunohistochemistry, two-dimensional gel electrophoresis
      including immunoblots, transmission electron microscopy, and soft agar suspension
      culture. After isolation of the tumor tissue under a stereodissection microscope,
      explants were cultured on feeder layers of mitomycin-treated 3T3 cells. After 3-5
      d, 73% of all explants of BCC could be successfully cultured showing spindle
      shaped outgrowing cells. Compared to nKC, cultured BCC cells had a lower growth
      rate and showed a wider intercellular polymorphism regarding size and shape.
      Their labeling pattern with a wide panel of monoclonal antibodies showed
      significant differences from that of nKC. In particular, only weak reactions for
      various cytokeratins, filaggrin and vimentin depending on the BCC cell type
      (small, middle, large) were found. Two-dimensional gel electrophoresis revealed
      expression of keratins 5, 6, 14, 16, and 17 in BCC cells and of K 5, 6, 13, 14,
      16, 17, and 19 in nKC. These findings were confirmed by immunoblot. On the
      ultrastructural level, only a few desmosomes and a lower degree of keratinization
      markers were detected in BCC cells; finally, when cultured in soft agar BCC cells
      formed colonies whereas nKC did not. Our findings indicate that cultured BCC
      cells may preserve in vitro some in vivo characteristics and maintain a growth
      and differentiation pattern that differs from cultured nKC. The culture model
      presented here provides further insights into the cytogenetic and histogenetic
      characteristics of BCC.

PMID- 1383351
TI  - Adhesion molecule expression in polymorphic light eruption.
AB  - Endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion
      molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are cytokine
      regulated cell-surface leukocyte adhesion molecules. We have investigated the in
      vivo kinetics and pattern of expression of these adhesion molecules in relation
      to tissue accumulation of leukocytes in the photodermatosis, polymorphic light
      eruption (PMLE), which is characterized by dense perivascular leukocytic
      infiltration. Immunohistology was performed on biopsies taken at varying time
      points from PMLE lesions induced in 11 subjects by suberythemal solar simulated
      irradiation. Vascular endothelial ELAM-1 expression was first observed at 5 h,
      maximal at 24 to 72 h, and remained elevated at 6 d. VCAM-1, minimally expressed
      in control skin, was induced above background levels on endothelium and some
      perivascular cells after 24 h and maintained at 6 d. Endothelial cell ICAM-1
      expression was increased above control levels at 72 h and 6 d. Keratinocyte ICAM
      1 expression, most marked overlying areas of dermal leukocytic infiltration,
      began at 5 h and was strong at 72 h and 6 d. In addition to lymphocytes,
      significant numbers of neutrophils but not eosinophils were detected in the
      dermal leukocytic infiltrate that appeared at 5 h and persisted at 6 d. The
      pattern of adhesion molecule expression that we have observed is similar to that
      seen in normal skin during a delayed hypersensitivity reaction. These
      observations support an immunologic basis for PMLE.

PMID- 1383352
TI  - Expression of simple epithelial keratins in epidermal neoplasia is not directly
      and exclusively related to malignancy.

PMID- 1383354
TI  - 1992 annual meeting of the International Society for Interferon Research (ISIR).
      Toronto, Ontario, Canada, September 28-October 2, 1992. Abstracts.

PMID- 1383353
TI  - Immune responsiveness to the immunodominant recombinant envelope epitopes of
      human T lymphotropic virus types I and II in diverse geographic populations.
AB  - The heterogeneity of immune responsiveness to the immunodominant epitopes of
      human T lymphotropic virus (HTLV) types I (MTA-1(162-209)) and II (K-55(162-205))
      were determined in natural infections with HTLV-I and -II from diverse geographic
      areas (n = 285). Of the HTLV-I specimens confirmed by polymerase chain reaction
      (PCR), all North American (n = 37) and Peruvian (n = 19) specimens reacted with
      MTA-1. Of HTLV-II specimens confirmed by PCR, 44 (96%) of 46 from North American
      blood donors, 28 (97%) of 29 from native Americans, and all from intravenous drug
      users (n = 29) reacted with K-55. Specimens from other geographic areas (Peru,
      30; Brazil, 4; Mexico, 10; Italy, 5; Somalia, 13; Ethiopia, 17; Japan, 32; and
      Jamaica, 15) all reacted either with MTA-1 or K-55. By synthetic peptide-based
      serologic typing, all of these specimens could be typed as HTLV-I or -II. In
      addition to the direct implications of these findings for diagnostic purposes,
      these data provide indirect evidence for the conservation of immunodominant
      HTLVenv epitopes in diverse geographic populations.

PMID- 1383355
TI  - Effect of recombinant human granulocyte colony-stimulating factor (G-CSF) in the
      treatment of Pseudomonas aeruginosa bacteremia complicating hematologic
      malignancy--a preliminary study.
AB  - The efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF)
      in the treatment of Pseudomonas aeruginosa bacteremia in cancer patients
      receiving intensive chemotherapy was studied retrospectively. In 14 of the 24
      episodes of P. aeruginosa bacteremia, which occurred in 23 severely neutropenic
      patients with hematologic malignancies during a three-year period, G-CSF was
      given subcutaneously or intravenously at daily doses of 75 micrograms/body to 200
      micrograms/m2 of body surface. Overall, survival at one week after onset was
      observed in 13 patients (54%). Treatment with G-CSF, however, had no
      statistically significant association with one-week survival, although a
      favorable outcome was well correlated with an increase in the neutrophil count
      during therapy. On the other hand, septic shock and appropriate antibiotic
      therapy were the major prognostic factors. The frequency of shock was reduced by
      appropriate therapy, but not by G-CSF treatment. These preliminary findings thus
      suggested that G-CSF should not be effective in the treatment of neutropenic
      cancer patients with P. aeruginosa bacteremia. No adverse effects of G-CSF were
      observed.

PMID- 1383356
TI  - [Development of serodiagnostic kit "HITAZYME Chlamydia Ab" for Chlamydia
      trachomatis infections using extracted antigen].
AB  - To develop EIA kit with low cross-reactivity for the quantitative detection of
      anti-chlamydial antibodies, we examined the preparation of trachomatis antigens
      and its specificity to mouse antisera and human sera. The chlamydial elementary
      body (EB) purified from C. trachomatis L2/434/Bu strain was treated by Sarkosyl,
      dithiothreitol and SDS by turns to obtain the soluble EB outer membrane (COMC).
      SDS-PAGE showed that the major components of the COMC were 96K, 60K and 39.5 KDa
      peptides. The reactivity of the COMC immobilized to 96 wells microtiter plate to
      mouse anti-serum to C. trachomatis was higher than the other two mouse anti-sera
      to C. psittaci and pneumoniae. In human sera, the cut off values were calculated
      from an average optical density plus its two-fold standard deviation obtained by
      the testing of 100 samples of healthy human sera. We evaluated the specificity of
      the kit to 17 anti-C. pneumoniae, 9 C. trachomatis and 4 C. psittaci antibodies
      positive patients' sera judged by the MFA method respectively. The results showed
      that the concordance ratio of IgG and IgA were 88%, 100% in anti-C. pneumoniae,
      89%, 78% in anti-C. trachomatis and 50%, 50% in anti-C. psittaci respectively.
      From the results obtained in this study, we concluded that the HITAZYME method
      which had a very low cross-reactivity to C. pneumoniae is clinically useful in
      the serodiagnosis of C. trachomatis infections, even if it has a little common
      antigenicity with C. psittaci antigen.

PMID- 1383357
TI  - A complete response of an advanced oesophageal carcinoma treated with
      hyperthermic chemotherapy: a case report.
AB  - A 56-year-old Japanese man with an advanced squamous cell carcinoma in the middle
      oesophagus was treated with a combination of hyperthermia, intravenous infusion
      of cisplatin (CDDP) and oral administration of oily bleomycin(BLM)-polyacrylate
      paste. After performing six sessions of hyperthermia treatment conducted at 42-45
      degrees C for 30 min with 150 mg of CDDP and 180 mg of BLM, a subtotal
      oesophagectomy and lymph node dissection were performed. A histopathological
      study of the resected specimen showed no residual viable cancer cells either in
      the oesophagus or in the dissected lymph nodes. There were no side effects or
      perioperative complications and the patient is now healthy and leading a normal
      life 10 months after operation without undergoing any further treatment, at the
      time of writing. The effect of small amounts of CDDP and the oral application of
      oily BLM were thought to be strongly enhanced by hyperthermia in the treatment of
      oesophageal squamous carcinoma, and this regimen is therefore recommended as a
      safe and effective strategy, especially for preoperative treatment.

PMID- 1383358
TI  - Interaction between the kinetics of thermotolerance and effect of cis
      diamminedichloroplatinum(II) or bleomycin given at 37 or 43 degrees C.
AB  - The interaction between the cytotoxic effect of bleomycin (BLM) or cis
      diamminedichloroplatinum(II) (cis-DDP) and the kinetics of thermotolerance was
      studied in cultured Chinese hamster ovary (CHO) cells. Pre-heated cells were
      treated with cis-DDP or BLM at 37 or 43 degrees C for various times after
      heating. Pre-heating enhanced cis-DDP cytotoxicity given immediately after
      heating, but this enhancement decreased within 24 h to an additive level. Cell
      survival following the initial heating and the second treatment of 'cis-DDP at 43
      degrees C was minimal when cis-DDP at 43 degrees C was given immediately after
      the initial heating, but became higher with increasing treatment interval and
      reached 'less than additive' level when the treatment interval was extended to
      more than 24 h. This alteration in cell survival appeared to follow the kinetics
      of thermotolerance. The interaction between BLM treatment and the kinetics of
      thermotolerance was similar to that of cis-DDP. However, pre-heating enhanced BLM
      cytotoxicity much less extensively than cis-DDP cytotoxicity. These results
      indicate that: (a) pre-heating of cells enhanced drug-toxicity when the drug was
      given shortly after heating, but the magnitude of this enhancement depended on
      the drug; (b) pre-heating did not influence the cytotoxicity of drugs given at 37
      degrees C; and (c) pre-heating decreased the magnitude of thermal sensitization
      of drug cytotoxicity. The magnitude of the decrease in thermal sensitization
      appeared to be parallel to the kinetics of thermotolerance. In this study it was
      also demonstrated that pre-treatment of CHO cells by cis-DDP or BLM did not alter
      sensitivity to subsequent drug treatment, hyperthermia or thermochemotherapy.

PMID- 1383360
TI  - [Rapid method for lipopolysaccharide analysis with deoxycholate-polyacrylamide
      gel electrophoresis and PAS stain].

PMID- 1383359
TI  - Effect of tumour necrosis factor, heat, and radiation on the viability and
      microfilament organization in cultured endothelial cells.
AB  - Normal blood vessels are leakage proof, non-adherent to blood cell elements, and
      participate actively in directional blood flow. These properties rely on the
      shape of endothelial cells and the integrity of the endothelial cell monolayer.
      The often observed effects of tumour necrosis factor-alpha (TNF) and hyperthermia
      on tumour tissue are the disruption of blood flow and an increase of vascular
      permeability. These agents are also known to affect the cytoskeletal organization
      and the cytoskeleton-dependent cellular functions. We observed that TNF (100 U/ml
      for 60 min) or heat (43 degrees C for 60 min) treatment causes the collapse of
      actin filaments in human umbilical vein endothelial cells (HUVEC). The combined
      treatment of TNF and hyperthermia intensifies the change of shape and loss of
      actin filaments. However, these changes are reversible within 24 h. These
      transient changes may contribute to the dysfunction and increased leakage of the
      microvasculature in tumours during and after these treatments despite the fact
      that the viability determined by MTT assay did not show a significant interaction
      between TNF and hyperthermia. Radiation (5 Gy) and TNF interact to a lesser
      extent compared with heat and TNF on cell shape and actin filament organization
      in HUVEC. Heat or radiation treatment enhances the expression of ELAM-1 mRNA in
      HUVEC while TNF produces the strongest effect on ELAM-1 mRNA expression. Our
      study suggests that radiation and heat affect endothelial cells and their
      subsequent functions differently. Result of an interaction between heat and TNF
      on endothelial cells supports the common notion that the anti-tumour effect by
      heat plus TNF treatments may benefit due to the increased disruption of
      vasculature function in the tumour.

PMID- 1383361
TI  - [Asthma due to airway inflammation].

PMID- 1383362
TI  - [Drug therapy of asthma by antiallergic agents].

PMID- 1383363
TI  - [Mechanism of leukemia cell proliferation].

PMID- 1383364
TI  - [Treatment of acute myelogenous leukemia].

PMID- 1383365
TI  - [Therapy of chronic myelogenous leukemia].

PMID- 1383366
TI  - [Bone marrow transplantation for therapy of leukemia].

PMID- 1383367
TI  - [Countermeasure for treatment of leukemia in the aged].

PMID- 1383368
TI  - [Treatment of leukemia: discussion].

PMID- 1383369
TI  - Regulation of T cell proliferation by anti-CD49d and anti-CD29 monoclonal
      antibodies.
AB  - The beta 1 integrin VLA-4 (alpha 4 beta 1, CD49d/CD29), which is expressed on a
      large subpopulation of peripheral blood T lymphocytes, functions as a receptor
      for the endothelial adhesion protein VCAM-1 and the extracellular matrix protein
      fibronectin. Previous studies showed that immobilized fibronectin enhanced anti
      CD3 monoclonal antibody (mAb)-induced T cell proliferation through binding to the
      integrins VLA-4 and VLA-5 (alpha 5 beta 1, CD49e/CD29). We studied the ability of
      the anti-CD49d mAb L25 to potentiate proliferation. T cell proliferation was
      induced by subthreshold concentrations of anti-CD3 mAb (mAb OKT3) coimmobilized
      with mAb L25 but not with coimmobilized anti-CD29 (beta 1) mAb. Soluble anti-CD29
      mAb inhibited the proliferation induced by coimmobilized mAb OKT3 and L25 but not
      proliferation induced by mAb OKT3 with PMA or coimmobilized anti-CD26 mAb.

PMID- 1383370
TI  - Antibodies to hepatitis C virus among patients with hepatocellular carcinoma and
      blood donors in Thailand.
AB  - HCC is the most cancer among Thai men. It is not known if HCV plays an oncogenic
      role in HCC in this country where HBV is endemic. Anti-HCV and HBsAg were assayed
      in 154 sera from HCC and 3,387 voluntary blood donors. The prevalence of anti-HCV
      in HCC (8.4%) was significantly higher than blood donors (1.38%). The prevalence
      of HBsAg in HCC (61%) was also significantly higher than blood donors (5.28%).
      The prevalence of anti-HCV in HCC was lower than that of Spain, Italy, Africa and
      Taiwan. Anti-HCV was found associated with a small portion of patients with HCC
      while HBV was found closely associated with the larger proportion of HCC. HCV in
      normal Thais was as common as those in southern Europe and HCV was found
      associated with HCC. However, HBV remains the major etiological factor of HCC in
      Thailand.

PMID- 1383371
TI  - Failure of parasystolic impulses to appear on schedule. Exit block due to
      concealed conduction of sinus impulses.
AB  - A 45-year-old patient free of any heart disease was admitted to the hospital with
      an electrocardiographic pattern of ventricular parasystole. The parasystolic
      rhythm was relatively fast, such that several consecutive ectopic complexes
      manifested. A later tracing reflected only isolated parasystolic complexes with
      long and fixed coupling intervals. The interectopic intervals, however, were once
      more in multiple of the parasystolic cycle as directly measured during the phases
      of undisturbed parasystolic rhythm. In the latter tracing, several scheduled
      parasystolic impulses did not yield a response, despite calculation suggesting
      that these impulses occurred outside the refractory period. In other words, an
      exit block was present. Analysis of the tracing suggests that the exit block was
      caused by concealed penetration of the sinus impulses into the ectopic
      ventricular junction. That is, any sinus impulse penetrates into the junction and
      renders it refractory, in such a way that only parasystolic impulses that are
      relatively late within the sinus cycle may be conducted to the surrounding
      myocardium and result in a parasystolic complex.

PMID- 1383372
TI  - Dextran particles as a carrier for Giardia lamblia for scanning electron
      microscopy.
AB  - Giardia lamblia trophozoites attach readily to dextran particles after which they
      can be conveniently processed for scanning electron microscopy. As the particles
      are spherical in shape, G. lamblia can be viewed from various directions and
      their morphology studied.

PMID- 1383373
TI  - Comparison of extraction methods for insulin-like growth factor-I in rat serum.
AB  - This study was undertaken to compare various extraction methods for insulin-like
      growth factor-binding proteins (IGFBPs) from insulin-like growth factor-I (IGF-I)
      in rat serum systematically, before measurement of IGF-I by radioimmunoassay
      (RIA). The values obtained in the IGF-I RIA following acid-ethanol (AE), acid
      ethanol cryoprecipitation (AEC) and formic acid-acetone (FA) extraction methods
      were compared with the IGF-I values obtained following high-performance liquid
      chromatography (HPLC), which was the reference method. Radioligand blots were
      used to determine the pattern and degree of IGFBP removal by these methods. Over
      a wide range of circulating IGF-I levels, AE and AEC extraction gave IGF-I levels
      comparable with those obtained following HPLC. FA extraction resulted in IGF-I
      levels that were consistently higher (P < 0.01) than those obtained following
      HPLC and gave non-parallel displacement curves in comparison with recombinant IGF
      I standards (P <0.01). Ligand blots demonstrated a similar pattern of IGFBP
      removal among the three methods with almost complete removal of IGFBP-3 but only
      30-40% removal of the lower molecular weight IGFBPs. These lower molecular weight
      IGFBPs did not interfere with the RIA measurements of IGF-I from AE and AEC
      extracts. Therefore the AE extraction method of Daughaday, originally validated
      for use in human serum, is also satisfactory for use in rat serum. The complete
      removal of IGF-binding activity does not appear essential for accurate
      measurement of IGF-I by RIA, although this may depend on the specific binding
      characteristics of the IGF-I antiserum.

PMID- 1383374
TI  - Investigation of the mechanism of action of growth hormone in stimulating
      lactation in the rat.
AB  - The role of GH was examined using an antiserum to rat GH (anti-rGH). When
      administered to lactating rats on day 2 of lactation it was without effect,
      whereas bromocriptine markedly suppressed milk production, with no additional
      effect of combined treatment. On day 6 of lactation, treatment with anti-rGH was
      also without effect, whilst bromocriptine again suppressed milk production.
      Combined treatment, however, suppressed milk synthesis completely, suggesting
      that GH was capable of maintaining about 50% of normal milk yield in the absence
      of prolactin at day 6 of lactation. By day 14 of lactation, anti-rGH treatment
      alone was capable of decreasing milk yield by about 20%, and again milk secretion
      only stopped completely when GH and prolactin were suppressed. These data suggest
      that the role of GH in supporting lactation increases as lactation progresses.
      The effects of GH in stimulating growth and in increasing milk yield in ruminants
      have been proposed to be mediated via insulin-like growth factor-I (IGF-I). In
      rats treated with anti-rGH, both IGF-I and IGF-II were decreased in serum. The
      concentration of the major IGF-binding protein (IGFBP-3) was not, however,
      affected by inhibition of GH or prolactin individually, but was decreased in
      animals treated with bromocriptine and anti-rGH. In animals given both
      bromocriptine and anti-rGH, concurrent treatment with recombinant bovine GH
      maintained milk yield at 50% of control values and normalized serum IGF-I, IGF-II
      and IGFBP-3 concentrations. By contrast, concurrent treatment with IGF-I or IGF
      II, despite normalizing their respective concentrations in serum, failed to
      affect milk yield.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383375
TI  - Helper virus induced T cell lymphoma in nonhuman primates after retroviral
      mediated gene transfer.
AB  - Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is
      not known to be a pathogen in primates. The core protein and enzyme genes of the
      MoMuLV genome together with an amphotropic envelope gene are utilized to engineer
      the cell lines that generate retroviral vectors for use in current human gene
      therapy applications. We developed a producer clone that generates a very high
      concentration of retroviral vector particles to optimize conditions for gene
      insertion into pluripotent hematopoietic stem cells. This producer cell line also
      generates a much lower concentration of replication-competent virus that arose
      through recombination. Stem cells from rhesus monkeys were purified by
      immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the
      presence of retroviral vector particles with accompanying replication-competent
      virus and used to reconstitute recipients whose bone marrow had been ablated by
      total body irradiation. The retroviral vector genome was detected in circulating
      cells of five of eight transplant recipients of CD34+ cells and in the
      circulating cells of two recipients of infected, unfractionated bone marrow
      mononuclear cells. Three recipients of CD34+ cells had a productive infection
      with replication-competent virus. Six or seven mo after transplantation, each of
      these animals developed a rapidly progressive T cell neoplasm involving the
      thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10
      50 copies of the replication-competent virus, but lacked the retroviral vector
      genome. We conclude that replication-competent viruses arising from producer
      cells making retroviral vectors can be pathogenic in primates, which underscores
      the importance of carefully screening retroviral producer clones used in human
      trials to exclude contamination with replication-competent virus.

PMID- 1383376
TI  - Expression of adhesion molecules and chemotactic cytokines in cultured human
      mesothelial cells.
AB  - The mesothelium is a flat epithelial lining of serous cavities that could gate
      the traffic of molecules and cells between the circulation and these body
      compartments. The present study was designed to elucidate the capacity of
      mesothelial cells to express adhesion molecules and chemoattractant cytokines,
      two fundamental mechanisms of regulation of leukocyte recruitment. Cultured human
      mesothelial cells express appreciable levels of intercellular adhesion molecule 1
      (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and these were increased
      by in vitro exposure to tumor necrosis factor (TNF), interferon gamma (IFN
      gamma), or TNF and IFN-gamma. Interleukin 1 (IL-1) was a less consistent stimulus
      for adhesion molecule expression in vitro. Unlike endothelial cells, used as a
      reference cell population, resting or stimulated mesothelial cells did not
      express E-selectin and ICAM-2, as assessed by flow cytometry. Analysis of VCAM-1
      mRNA by reverse transcriptase and polymerase chain reaction using appropriate
      primers revealed that mesothelial cells expressed both the seven- and the six-Ig
      domain transcripts, with predominance of the longer species. Monocytes bound
      appreciably to "resting" and, to a greater extent, to stimulated mesothelial
      cells. Monocytes exposed to IFN-gamma and lipopolysaccharide, used as prototypic
      activation signals, showed increased capacity to bind mesothelial cells. Anti
      CD18 monoclonal antibody significantly inhibited binding of monocytes to
      mesothelial cells, and this blocking effect was amplified by anti-very late
      antigen 4. Mesothelial cells were able to express the chemotactic cytokines IL-8
      and monocyte chemotactic protein 1 at the mRNA and protein levels. These results
      indicate that mesothelial cells can express a set of adhesion molecules (ICAM-1
      and VCAM-1) overlapping with, but distinct from, that expressed in vascular
      endothelium (ICAM-1, ICAM-2, VCAM-1, E-selectin), and that these are functionally
      relevant for interacting with mononuclear phagocytes. The regulated expression of
      adhesion molecules and chemotactic cytokines by mesothelial cells is probably
      important in inflammatory and immune reactions that involve serous cavities, such
      as the long-known macrophage appearance and disappearance reactions.

PMID- 1383377
TI  - N omega-amino-L-arginine, an inhibitor of nitric oxide synthase, raises vascular
      resistance but increases mortality rates in awake canines challenged with
      endotoxin.
AB  - Inhibitors of nitric oxide synthase (NOS) have been reported to increase mean
      arterial pressure in animal models of sepsis and recently have been given to
      patients in septic shock. However, controlled studies to determine the effects of
      these agents on cardiovascular function and survival in awake animal models of
      sepsis have not been reported. To examine the therapeutic potential of NOS
      inhibition in septic shock, we challenged canines with endotoxin (2 or 4 mg/kg
      i.v.) and treated them with either normal saline or N omega-amino-L-arginine (10
      or 1 mg/kg/h), the most specific inhibitor available for the isoform of NOS
      implicated in septic shock. Endotoxemic animals treated with N omega-amino-L
      arginine (n = 11) had higher systemic and pulmonary vascular resistance indices
      (SVRI and PVRI, p less than or equal to 0.033) and decreased heart rates (p =
      0.009), cardiac indices (CI, p = 0.01), oxygen delivery indices (p = 0.027), and
      oxygen consumption indices (p = 0.046) compared with controls (n = 6). Moreover,
      N omega-amino-L-arginine increased mortality rates after endotoxin challenge (10
      of 11 vs. 1 of 6 controls, p = 0.005). Administration of L-arginine did not
      improve survival or alter the cardiopulmonary effects of N omega-amino-L
      arginine, which suggests that inhibition of NOS may not have been competitive. In
      normal animals, N omega-amino-L-arginine alone (n = 3) increased SVRI (p =
      0.0008) and mean arterial pressure (p = 0.016), and decreased CI (p = 0.01)
      compared with saline-treated controls (n = 3), but, at the high dose, also
      produced neuromuscular rigidity and seizure-like activity that was not apparent
      in the endotoxemic model. Thus, the mortality rate from endotoxemia increased
      either because of NOS inhibition per se or because of properties unique to N
      omega-amino-L-arginine, or both.

PMID- 1383378
TI  - Human vascular endothelial cell adhesion receptors for Plasmodium falciparum
      infected erythrocytes: roles for endothelial leukocyte adhesion molecule 1 and
      vascular cell adhesion molecule 1.
AB  - The clinical complications associated with severe and cerebral malaria occur as a
      result of the intravascular mechanical obstruction of erythrocytes infected with
      the asexual stages of the parasite, Plasmodium falciparum. We now report that a
      primary P. falciparum-infected erythrocyte (parasitized red blood cell [PRBC])
      isolate from a patient with severe complicated malaria binds to cytokine-induced
      human vascular endothelial cells, and that this adhesion is in part mediated by
      endothelial leukocyte adhesion molecule 1 (ELAM-1) and vascular cell adhesion
      molecule 1 (VCAM-1). PRBC binding to tumor necrosis factor alpha (TNF-alpha)
      activated human vascular endothelial cells is partially inhibited by antibodies
      to ELAM-1 and ICAM-1 and the inhibitory effects of these antibodies is additive.
      PRBCs selected in vitro by sequential panning on purified adhesion molecules bind
      concurrently to recombinant soluble ELAM-1 and VCAM-1, and to two previously
      identified endothelial cell receptors for PRBCs, ICAM-1, and CD36. Post-mortem
      brain tissue from patients who died from cerebral malaria expressed multiple cell
      adhesion molecules including ELAM-1 and VCAM-1 on cerebral microvascular
      endothelium not expressed in brains of individuals who died from other causes.
      These results ascribe novel pathological functions for both ELAM-1 and VCAM-1 and
      may help delineate alternative adhesion pathways PRBCs use to modify malaria
      pathology.

PMID- 1383379
TI  - Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by
      IL-4 in human B cells.
AB  - The effect of interleukin 8 (IL-8) on IL-4-induced immunoglobulin E (IgE)
      production was studied. IL-4 induced IgE and IgG4 production by tonsillar
      mononuclear cells (MNC) without affecting IgM, IgG1, IgA, IgG2, or IgG3
      production. IL-8 inhibited IL-4-induced IgE and IgG4 production, whereas it had
      no effect on IgM, IgG1, IgA, IgG2, and IgG3 production. The inhibitory effect by
      IL-8 was specific, since it was blocked by anti-IL-8 mAb, but not by control
      IgG1. Although interferon gamma (IFN-gamma) also inhibited IgE and IgG4
      production by MNC stimulated with IL-4, the inhibitory effect of IL-8 was not
      mediated by IFN-gamma, since the IL-8-induced inhibition could not be blocked by
      anti-IFN-gamma. Furthermore, anti-IL-8 mAb had no effect on IFN-gamma-induced
      inhibition. Moreover, addition of IL-5 or IL-6 did not reverse IL-8-induced
      inhibition of IgE production. In contrast to these observations with MNC, IL-4
      failed to induce IgE and IgG4 production by purified B cells. However, combined
      treatment of purified B cells cells with IL-4 and anti-CD40 antibody resulted in
      IgE but not IgG4 production. IL-8 inhibited this IgE production without affecting
      IgM, IgG1, IgG2, IgG3, IgG4, or IgA production, whereas IFN-gamma, IFN-alpha, or
      prostaglandin E2 (PGE2) failed to do so. These results indicate that IL-8
      antagonizes IL-4-induced IgE production by directly affecting B cells through a
      specific mechanism that is different from IFN-gamma, IFN-alpha, or PGE2.

PMID- 1383380
TI  - Highly restricted expression of a stromal cell determinant in mouse bone marrow
      in vivo.
AB  - B lymphocyte precursor cells in mouse bone marrow develop in close association
      with stromal cells which provide essential growth signals. To identify molecules
      that may normally play a role in this interaction we have examined the in vivo
      binding of a new monoclonal antibody (mAb) (KMI6) that recognizes a determinant
      on a bone marrow stromal cell line (BMS2) in vitro. Flow cytometric and
      radioautographic evaluations revealed that the antigen recognized by KMI6 is
      represented on the surface of an extremely small number of cells in bone marrow
      cell suspensions from adult mice. An apparent molecular mass of 110 kD was
      obtained by surface labeling of a stromal cell clone and immunoprecipitation.
      Purified mAb KMI6 labeled with 125I was then given intravenously to young C3H/HeJ
      mice. Unbound mAb was washed out by cardiac perfusion and femoral bone marrow was
      examined by light and electron microscope radioautography. KMI6 labeling was
      heavy on the plasma membrane of many stromal cells, especially those located
      towards the outer subosteal region. The KMI6-labeled stromal cells were usually
      associated with cells of lymphoid morphology which they often completely
      surrounded. The labeling was restricted to areas of stromal cell plasma membranes
      in contact with lymphoid cells. The lymphoid cells themselves, as well as
      macrophages and other hemopoietic cells, failed to bind mAb KMI6 significantly.
      Stromal cells in bone marrow depleted of hemopoietic cells by gamma-irradiation
      (9,5 Gy) bound mAb KMI6 at reduced intensity. The results demonstrate that the
      KMI6 determinant, a 110-kD protein, is expressed on bone marrow stromal cells in
      vivo. Its restriction to areas of interaction with lymphoid cells suggests a role
      in forming microenvironmental niches of B lymphopoiesis. The surface membrane of
      individual stromal cells may thus be functionally polarized towards interacting B
      cell precursors and other hemopoietic cells.

PMID- 1383381
TI  - Distinctive polymorphism at the HLA-C locus: implications for the expression of
      HLA-C.
AB  - The HLA-C locus remains an enigma. The serological polymorphism is poorly
      defined, HLA-C molecules are expressed at the cell surface at about 10% the
      levels of HLA-A and -B, and their importance for antigen presentation to either
      CD8-bearing T cells or natural killer cells is unclear. Our understanding of HLA
      C polymorphism has also lagged behind that of HLA-A and -B. We have applied the
      polymerase chain reaction to the characterization of cDNA encoding HLA-C
      antigens. Combining the recent results with previously characterized HLA-C
      alleles gives a data base of 26 sequences, which was used to analyze the nature
      of HLA-C polymorphism and compare it to the variation seen in HLA-A and -B. The
      sequences form 10 families of alleles that correlate well with the patterns of
      serological crossreactivity, including the C blanks, and all major HLA-C allelic
      families appear to have been sampled. The families further divide into two groups
      of HLA-C alleles defined on the basis of linked substitutions in the 3' exons. In
      comparison with HLA-A and -B, HLA-C alleles are more closely related to each
      other, there being less variation in residues of the antigen recognition site and
      more variation at other positions. In particular, the helix of the alpha 1 domain
      of HLA-C molecules is unusually conserved. Despite the reduced diversity in the
      antigen recognition site, it is evident that HLA-C genes have been the target of
      past selection for polymorphism. Within the antigen recognition site, it is the
      alpha 1 domain that is most diagnostic of HLA-C, whereas the alpha 2 domain is
      similar to that of HLA-B, the locus to which HLA-C is most closely related. In
      particular, conserved motifs in the alpha 1 helix and the conserved glycine at
      the base of the B pocket (position 45) provide a combination of features that is
      uniquely found in HLA-C molecules. We hypothesize that these features restrict
      the peptides bound by HLA-C molecules and in this manner reduce the efficiency of
      HLA-C assembly and expression at the cell surface. The overall picture HLA-C
      polymorphism obtained from this sampling of HLA-C alleles is unlikely to change
      as further alleles are characterized.

PMID- 1383382
TI  - Cloning and characterization of the cDNA coding for a polymyositis-scleroderma
      overlap syndrome-related nucleolar 100-kD protein.
AB  - About 50% of patients with the polymyositis-scleroderma overlap syndrome are
      reported to have autoantibodies to a nucleolar particle termed PM/Scl. The
      particle consists of several polypeptides of which two proteins of 75 and 100 kD
      have been identified as the major antigenic components. Here we report on the
      cDNA cloning and partial epitope mapping of the 100-kD autoantigen from human
      placenta and HeLa lambda gt11 libraries. The deduced amino acid sequence encodes
      a protein of 885 amino acid residues with a molecular mass of 100.8 kD. Rabbit
      antibodies raised against a recombinant protein fragment reacted in
      immunofluorescence and immunoblotting in the same manner as human autoantibodies
      directed against the nucleolar 100-kD protein. Sequence analysis shows close
      homology to a consensus sequence of 12 amino acids from serine/threonine kinases,
      suggesting a possible function for this autoantigen. A major antigenic region is
      found to be located within the NH2-terminal third of the polypeptide.

PMID- 1383383
TI  - CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation.
AB  - CD2 is an intercellular adhesion molecule that has been implicated in T cell
      activation and differentiation both in humans and mice. Although the ligand for
      human CD2 has been defined as LFA-3, that for murine CD2 has not been identified
      yet. To identify the ligand for mouse CD2, we generated a chimeric molecule
      consisting of the extracellular domain of mouse CD2 and human immunoglobulin
      (Ig)G1 Fc (mCD2Rg). A hamster monoclonal antibody (mAb), HM48-1, was established
      by screening mAbs that could block the binding of mCD2Rg to T cell lines at the
      ligand site. The putative mouse CD2 ligand recognized by this mAb was a glycosyl
      phosphatidylinositol-anchored glycoprotein with an apparent molecular mass of 45
      kD, which were shared characteristics with human LFA-3. However, its expression
      was predominantly restricted to hematopoietic cells, unlike human LFA-3. Protein
      microsequencing analysis for the NH2-terminal 18 amino acid residues of the
      affinity-purified HM48-1 antigen revealed that it is almost identical with mouse
      CD48. This identity was further confirmed by the reactivity of HM48-1 with a
      soluble recombinant CD48 (sCD48) protein and the molecule recognized by a rat mAb
      raised against sCD48. A rat anti-CD48 mAb blocked the mCD2Rg binding as well as
      HM48-1. Moreover, sCD48 also inhibited the mCD2Rg binding to the cellular ligand.
      Finally, like anti-CD2 mAb, HM48-1 inhibited the phytohemagglutinin response and,
      when crosslinked, augmented the anti-CD3 response of splenic T cells. These
      results indicate that CD48 is a ligand for mouse CD2 and is involved in
      regulating T cell activation.

PMID- 1383384
TI  - CD8+ T cell recognition of an endogenously processed epitope is regulated
      primarily by residues within the epitope.
AB  - Cytotoxic T lymphocytes (CTL) recognize short antigenic peptides associated with
      cell surface class I major histocompatibility complex (MHC) molecules. This
      association presumably occurs between newly synthesized class I MHC molecules and
      peptide fragments in a pre-Golgi compartment. Little is known about the factors
      that regulate the formation of these antigenic peptide fragments within the cell.
      To examine the role of residues within a core epitope and in the flanking
      sequences for the generation and presentation of the newly synthesized peptide
      fragment recognized by CD8+ CTL, we have mutagenized the coding sequence for the
      CTL epitope spanning residues 202-221 in the influenza A/Japan/57 hemagglutinin
      (HA). In this study over 60 substitution mutations in the epitope were tested for
      their effects on target cell sensitization using a cytoplasmic viral expression
      system. The HA202-221 site contains two overlapping subsites defined by CTL
      clones 11-1 and 40-2. Mutations in HA residues 204-213 or residues 210-219 often
      abolished target cell lysis by CTL clones 11-1 and 40-2, respectively. Although
      residues outside the core epitope did not usually affect the ability to be lysed
      by CTL clones, substitution of a Gly residue for Val-214 abolished lysis by clone
      11-1. These data suggest that residues within a site that affect MHC binding and
      T cell receptor recognition appear to play the predominant role in dictating the
      formation of the antigenic complex recognized by CD8+ CTL, and therefore the
      antigenicity of the protein antigen presented to CD8+ T cells. Most alterations
      in residues flanking the endogenously expressed epitope do not appreciably affect
      the generation and recognition of the site.

PMID- 1383385
TI  - Oral tolerance to myelin basic protein and natural recovery from experimental
      autoimmune encephalomyelitis are associated with downregulation of inflammatory
      cytokines and differential upregulation of transforming growth factor beta,
      interleukin 4, and prostaglandin E expression in the brain.
AB  - Experimental autoimmune encephalomyelitis (EAE) in the Lewis rat is a self
      limited inflammatory process localized to the central nervous system that is
      induced by the injection of myelin basic protein (MBP) in adjuvant. Oral
      administration of MBP suppresses EAE, and this suppression is mediated by CD8+ T
      cells that adoptively transfer protection and suppress both in vitro and in vivo
      by the release of transforming growth factor (TGF) beta after antigen-specific
      triggering. Furthermore, oral tolerance to MBP is enhanced by the concomitant
      oral administration of lipopolysaccharide (LPS). The present study was undertaken
      to determine whether the disease course in EAE and its suppression by oral
      tolerization to MBP is associated with distinct patterns of cytokine expression
      in the target organ. Detailed immunohistology of the brain was performed at the
      peak of clinical disease (day 14 after immunization) and after recovery (day 18)
      in control (ovalbumin [OVA]-fed), MBP-fed, and MBP plus LPS-fed animals. Brains
      from OVA-fed animals at the peak of disease showed perivascular infiltration with
      activated mononuclear cells which secreted the inflammatory cytokines
      interleukins (IL) 1, 2, 6, 8, TNF-alpha, and interferon gamma. The inhibitory
      cytokines TGF-beta and IL-4, and prostaglandin E2 (PGE2) were absent. In MBP
      orally tolerized animals there was a marked reduction of the perivascular
      infiltrate and downregulation of all inflammatory cytokines. In addition, there
      was upregulation of the inhibitory cytokine TGF-beta. In MBP plus LPS orally
      tolerized animals, in addition to upregulation of TGF-beta and reduction of
      inflammatory cytokines, there was enhanced expression of IL-4 and PGE2,
      presumably secondary to activation of an additional population of
      immunoregulatory cells. In OVA-fed animals that had recovered (day 18), staining
      for inflammatory cytokines diminished, and there was the appearance of TGF-beta
      and IL-4. These results suggest that suppression of EAE, either induced by oral
      tolerization or that which occurs during natural recovery is related to the
      secretion of inhibitory cytokines or factors that actively suppress the
      inflammatory process in the target organ.

PMID- 1383387
TI  - Identification of a soluble form of a ligand for the lymphocyte homing receptor.
AB  - Lymphocytes are engaged in constant trafficking from the blood into secondary
      lymphoid tissues, such as peripheral lymph nodes (PLN), mesenteric lymph nodes
      (MLN), and Peyer's patches (PP). The initial step in this process is the binding
      of lymphocytes to high endothelial venules (HEV), and in the case of trafficking
      of cells to the PLN, it is required that they bear the L-selectin surface
      receptor. Using a chimeric protein, combining the extracellular domains of L
      selectin with a human immunoglobulin (Ig) G1 Fc region (L-selectin-IgG), we have
      probed the expression of ligands for this receptor on HEV and in cell lysates.
      Two sulfated glycoproteins of 50 and 90 kD have been identified in lysates from
      PLN and MLN, but not PP. Here we show that the 50-kD molecule is secreted in
      organ cultures in vitro and is present in the blood of normal animals. Indeed,
      normal serum inhibits lymphocyte binding to HEV by approximately 50% in an in
      vitro assay. This inhibitory activity can be removed by passage of the serum over
      an L-selectin-IgG column and has a molecular mass of approximately 50 kD. We
      speculate on the possible reasons for secretion of a homing receptor ligand.

PMID- 1383386
TI  - Characterization of an Epstein-Barr virus receptor on human epithelial cells.
AB  - Epstein-Barr virus (EBV) adsorption to human B lymphocytes is mediated by the
      viral envelope glycoprotein, gp350/220, which binds to the cell surface protein,
      CD21, also known as the CR2 complement receptor. Human epithelial cells also
      express an EBV receptor. A candidate surface molecule of 195 kD has previously
      been identified on an epithelial cell line and explanted epithelial tissue by
      reactivity with the CD21 specific monoclonal antibody (mAb), HB-5a. In
      experiments to further characterize the epithelial cell EBV receptor, we have
      found that two human epithelial cell lines, RHEK-1 and HeLa, specifically bind
      intact EB virions. A 145-kD protein, similar in size to B lymphocyte CD21, was
      specifically precipitated from surface iodinated RHEK-1 cells using the HB-5a
      mAb, or using purified soluble gp350/220 coupled to agarose beads. The previously
      identified 195-kD protein did not bind to gp350/220 or react with two other anti
      CD21 mAbs. CD21 homologous RNA, similar in size to the B lymphocyte CD21 mRNA,
      was detected in both RHEK-1 and HeLa cells. The nucleotide sequence of the
      epithelial cell cDNA was identical to B lymphocyte CD21. The longest clone
      differs from previously reported CD21 cDNAs in having additional 5' untranslated
      sequence. Polymerase chain reaction amplification of RHEK-1- or B lymphoblastoid
      derived cDNA verified that most CD21 transcripts are initiated at least 30-50
      nucleotides upstream of the previously reported mRNA cap site. These experiments
      demonstrate that human epithelial cells can express CD21, and that CD21 is likely
      to mediate EBV adsorption to epithelial cells.

PMID- 1383388
TI  - Soluble intercellular adhesion molecule 1-immunoglobulin G1 immunoadhesin
      mediates phagocytosis of malaria-infected erythrocytes.
AB  - We describe an immunoadhesin molecule containing intercellular adhesion molecule
      1 (ICAM-1) molecularly fused to hinge and CH2 and CH3 domains of the human
      immunoglobulin G1 H chain that binds Plasmodium falciparum-infected erythrocytes.
      This receptor-based immunoadhesin is an effective and specific inhibitor of P.
      falciparum-infected erythrocyte adhesion to ICAM-1-bearing surfaces, but does not
      inhibit leukocyte function antigen 1 (LFA-1) interaction with ICAM-1.
      Furthermore, the immunoadhesin promotes phagocytosis and destruction of
      parasitized erythrocytes by human monocytes. Each of these modes of action has
      potential for the therapy of malaria.

PMID- 1383390
TI  - Maternal serum alpha-fetoprotein testing: physician experience and attitudes and
      their influence on patient acceptance.
AB  - BACKGROUND: Maternal serum alpha-fetoprotein (MSAFP) testing is complex and
      controversial. Although patient response to testing has been studied extensively,
      physician experience with and attitudes toward the test have not been
      investigated. The purpose of this study was to describe family physician
      experience with MSAFP testing and determine if physician characteristics and
      attitudes influence whether the test is offered and whether patients accept it.
      METHODS: Eight hundred forty-nine Minnesota members of the American Academy of
      Family Physicians who provide prenatal care were surveyed by mail. Statistical
      analyses were performed, comparing physician characteristics, their offering of
      the test, and patient acceptance of the test. RESULTS: The survey response rate
      was 84%. Eighty-seven percent of the physicians offered MSAFP testing, most of
      them routinely. However, relatively few patients chose to have the test done.
      Physicians had concerns about the cost of the test and its effect on maternal
      anxiety. The strongest predictor of offering the test was whether the physician
      agreed it was "medically-legally necessary." CONCLUSIONS: Although most Minnesota
      family physicians offer MSAFP testing they have concerns about the test and its
      limitations and appear to convey these concerns to their patients.

PMID- 1383391
TI  - Voltage-dependent block of fast chloride channels from rat cortical neurons by
      external tetraethylammonium ion.
AB  - Tetraethylammonium ion (TEA) and its longer chain derivatives have been used
      extensively to block currents through K-selective ion channels. Substantial
      information has been gained about the structure and gating mechanisms of K and
      other cation channels from the analysis of the blocking interactions of TEA and
      other quaternary ammonium ions. We now present an analysis of blocking
      interactions between single Cl-selective ion channels from acutely dissociated
      rat cortical neurons and externally applied TEA. TEA applied to the extracellular
      membrane surface (TEAo) blocked Cl channels in a voltage-dependent manner, with
      hyperpolarizing potentials favoring block. The voltage dependence of block could
      be adequately fit assuming that TEA enters the channel pore and binds to a site
      located approximately 28% of the way through the membrane electrical field. The
      dose-response relationship between fractional current and [TEA]o at a fixed
      holding potential of -40 mV was well fit to a simple model with two blocking
      sites with dissociation constants (Kd) of approximately 2 and 70 mM. The dose
      response relationship could also be fit by a mechanism where TEA only partially
      blocks the channels. At the bandwidth used in these experiments (1-2 kHz), both
      the mean open duration (composed of the open and blocked durations) and burst
      duration (composed of open, blocked, and short lifetime shut durations) increased
      with increased [TEA]o. This is expected if TEAo can bind and unbind only when the
      channel is in the open kinetic state. These results suggest that the structure of
      the permeability pathway of these anion-selective channels may be very similar to
      that of other channels that are blocked by TEA. Additionally, these results
      caution that a blocking effect by TEA cannot, by itself, be used as sufficient
      evidence for implicating the participation of K channels in a particular process.

PMID- 1383389
TI  - Adjuvant-dependent immune response to malarial transmission-blocking vaccine
      candidate antigens.
AB  - Immune responses in major histocompatibility complex (MHC)-disparate congenic
      mouse strains immunized with sexual stage malaria parasites or purified
      recombinant protein were adjuvant dependent. Whereas mice exhibited a limited
      antibody response to immunization with newly emerged Plasmodium falciparum
      gametes in Freund's adjuvant, all five congenic mouse strains responded to
      several transmission-blocking vaccine candidate antigens, when parasites were
      emulsified in a monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM)
      adjuvant. The humoral response in those animals immunized with the antigen in a
      MPL/TDM adjuvant was helper T cell dependent, as evident by boosting of the
      antibody response after a second immunization. If the immunogen consisted of
      purified recombinant protein, then the immune response was not MHC class II
      limited in mice immunized with either complete Freund's adjuvant or TDM/MPL. The
      potential role of adjuvants in overcoming apparent immune nonresponsiveness and
      the implications for development of a malaria transmission-blocking vaccine are
      discussed.

PMID- 1383392
TI  - Adherence epitopes of Mycoplasma genitalium adhesin.
AB  - The adherence-mediating sites of the 153 kDa adhesin of Mycoplasma genitalium
      (MgPa-protein) were characterized at the amino acid sequence level using six
      monoclonal anti-MgPa antibodies which showed adherence-inhibiting activity. For
      characterization of the regions to which antibody bound, three segments of the
      adhesin (N-terminal region, a D1-domain located approximately in the middle of
      the molecule and a D2-domain located near to the C-terminus) were synthesized as
      overlapping octapeptides. These regions were chosen in analogy to the three
      domains of Mycoplasma pneumoniae that are involved in the adhesion process.
      Whereas two monoclonal antibodies (mAb 5B11 and mAb 6F3) bound exclusively to an
      epitope in the N-region, mAb 3B7 and mAb 6A2 reacted with two distinct epitopes
      of the D2-domain only. Binding to short synthetic peptides of different regions
      was analysed for mAb 3A12 (N-region and D1-region) and mAb 2B6 (N-region and D2
      region). Close proximity of the N-region and the D2-region in the native MgPa
      protein of M. genitalium was indicated in a competitive ELISA test, using freshly
      harvested M. genitalium cells. Epitope mapping and competition experiments with
      monoclonal anti-MgPa antibodies revealed interesting differences in the adherence
      mediating sites of MgPa and the adhesin (P1-protein) of M. pneumoniae. Whereas a
      three-dimensional arrangement of protein loops is suggested for both native
      adhesins, the MgPa-protein and the P1-protein adherence-mediating epitopes are
      located in non-homologous regions of these two related proteins.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1383393
TI  - Sequence and structural analysis of the rfb (O antigen) gene cluster from a group
      C1 Salmonella enterica strain.
AB  - The rfb (O antigen) gene cluster of a group C1 Salmonella enterica strain was
      sequenced; it comprised seven open reading frames which precisely replaced the 16
      open reading frames of a group B strain. Two genes of the mannose biosynthetic
      pathway were present: rfbK (phosphomannomutase) had a G+C content of 0.61 and had
      only 40% identity to rfbK of group B but was very similar to cpsG of the capsular
      polysaccharide pathway with 96% identity, whereas rfbM [guanosine
      diphosphomannose (GDP-Man) pyrophosphorylase] had a G+C content of 0.39. Other
      genes had G+C contents ranging from 0.24 to 0.28. rfbM(C1) and rfbM(B) had 60%
      identity, which is much less than expected within a species, but nonetheless
      indicates a much more recent common ancestor than for rfbK. The other genes
      showed much lower or no similarity to rfb genes of other S. enterica strains. It
      appears that the gene cluster evolved outside of Salmonella in a species with low
      G+C content: the rfbM gene presumably derives from that period whereas the rfbK
      gene appears to have arisen after transfer of the cluster to S. enterica by
      duplication of the S. enterica cpsG gene, presumably replacing an rfbK gene of
      low G+C content.

PMID- 1383394
TI  - Pear blister canker viroid is a member of the apple scar skin subgroup
      (apscaviroids) and also has sequence homology with viroids from other subgroups.
AB  - The sequence of pear blister canker viroid (PBCVd), the putative causal agent of
      pear blister canker (PBC) disease, has been determined. PBCVd consists of a
      single-stranded circular RNA of 315 nucleotide residues which assumes a branched
      conformation when it is folded in the model of lowest free energy. PBCVd has
      highest sequence similarity with grapevine 1B viroid (52.4%), but also contains
      sequences related to regions present in viroids that belong to different
      subgroups, suggesting that PBCVd could have developed from RNA recombination
      between viroids replicating in a common host plant. PBCVd contains almost the
      entire central sequence which is conserved in the members of the apple scar skin
      subgroup (apscaviroids) as well as a conserved sequence located in the left
      terminal region of apscaviroids and pospiviroids (whose type member is potato
      spindle tuber viroid). A consensus phylogenetic tree has been obtained in which
      PBCVd and other viroids previously classified as apscaviroids appear closely
      related, allowing consideration of PBCVd as a new member of this subgroup.

PMID- 1383395
TI  - Replication of grapevine fanleaf virus satellite RNA transcripts in Chenopodium
      quinoa protoplasts.
AB  - A set of full-length cDNA clones of the satellite RNA of grapevine fanleaf
      nepovirus isolate F13 (GFLV-F13) was constructed with a variable number of
      additional, non-viral nucleotides at the 5' and 3' ends. The biological activity
      of the RNAs transcribed from these constructs was tested in Chenopodium quinoa
      protoplasts using a helper virus. When inoculated with arabis mosaic virus S
      (ArMV-S) RNA as helper, transcripts with 33 non-viral nucleotides at the 5' end
      (tr45p4) did not replicate, whereas transcripts with only one non-viral
      nucleotide at the 5' end (tr3S and tr3M) did replicate. Capping of the
      transcripts enhanced their replication. On the other hand, the presence of extra
      nucleotides at the 3' end had little influence on the biological activity of the
      in vitro transcripts. In contrast with ArMV-S, GFLV isolate 24 was not a helper
      for tr3M transcripts, indicating a specific interaction between the helper strain
      and the satellite RNA.

PMID- 1383396
TI  - Idiotypic expression of anti-gp120 antibodies in unrelated human immunodeficiency
      virus-infected individuals.
AB  - Although it is recognized that human immunodeficiency virus (HIV) env genes
      exhibit a high degree of variability, little is known about the molecular
      heterogeneity of gp120-specific antibodies in infected individuals. As a first
      step to approach this issue, we investigated the idiotypic relatedness of anti
      gp120 antibodies present in the serum of HIV-infected individuals. Idiotypic
      determinants (idiotopes) are fingerprints of the variable region of the antibody
      molecule and, as such, they represent unique probes with which to explore the
      diversity of the immune response. We isolated IgG anti-gp120 antibodies from the
      serum of a seropositive asymptomatic individual by affinity chromatography. The
      purified antibodies were shown to bind gp120 and gp160 by ELISA, Western blotting
      and radio-immunoprecipitation. They also recognized HIV-infected human T cells as
      detected by immunofluorescence. Anti-idiotypic reagents were generated against
      this gp120 idiotype, and one of them was used to study anti-gp120 idiotypic
      diversity in a panel of 65 sera drawn from AIDS and AIDS-related complex
      patients, and from HIV seropositive asymptomatic individuals. Sixty normal human
      sera were used as negative controls. We found no evidence for common idiotopes on
      anti-gp120 antibodies of unrelated individuals. In contrast, we also noticed that
      the idiotypic profile expressed sequentially at two different intervals in a
      persistently infected individual showed little variation. Finally, when the
      diversity of murine anti-gp120 antibodies with a monoclonal anti-idiotype was
      analysed, no evidence of cross-reactive idiotopes in the murine system was found.

PMID- 1383397
TI  - Location of the epitope recognized by monoclonal antibody 63G on the primary
      structure of human respiratory syncytial virus G glycoprotein and the ability of
      synthetic peptides containing this epitope to induce neutralizing antibodies.
AB  - The location of the epitope recognized by monoclonal antibody (MAb) 63G on the
      primary structure of the human respiratory syncytial virus G glycoprotein was
      determined by testing the reactivity of synthetic peptides with the MAb. The role
      of individual amino acids in this epitope was determined by using a set of 13-mer
      peptides containing single residue deletions. Residues 204 to 209 were found to
      be essential for antibody binding. These results are in full agreement with
      previous sequence data for escape mutants selected with MAb 63G. Several
      peptides, free or bound to keyhole limpet haemocyanin (KLH), were used to raise
      antisera in rabbits. The antipeptide antibodies reacted with the G protein in
      Western blots. However, only peptide G1-KLH (residues 187 to 200 bound to KLH)
      induced antibodies that reacted with the intact G protein and inhibited
      infectivity. These findings are discussed in terms of the antigenic structure of
      the G glycoprotein and the molecular engineering of peptide antigens.

PMID- 1383398
TI  - Monoclonal antibody E-13 (M-810) to human cytomegalovirus recognizes an epitope
      encoded by exon 2 of the major immediate early gene.
AB  - Monoclonal antibody (MAb) E-13 to human cytomegalovirus is used widely for
      diagnostic and fundamental studies, and has been shown to be directed against an
      immediate early (IE) protein(s). To determine which viral antigen is detected by
      MAb E-13, four subfragments from the open reading frame encoded by exons 2, 3 or
      4 of IE-1 were cloned in the bacterial expression vector pROS. The resulting
      fusion proteins contained amino acids 77 to 491 encoded by mainly exon 4, amino
      acids 25 to 78 encoded by exon 3, amino acids 1 to 85 encoded by exons 2 and 3,
      and amino acids 1 to 24 encoded by exon 2. The reactivity of MAb E-13 with the
      fusion proteins was assayed by Western blotting. MAb E-13 was shown to react
      exclusively with proteins encoded by exon 2 and therefore recognizes IE proteins
      which contain the N-terminal amino acid sequence encoded by exon 2, namely the
      major 72K IE protein, the 82K to 86K IE-2 protein and the 52K to 55K IE-2
      protein. MAb E-13 can be used to detect both IE-1- and IE-2-encoded proteins,
      which share the polypeptide encoded by exon 2.

PMID- 1383399
TI  - Identification of a gag protein epitope conserved among all four groups of
      primate immunodeficiency viruses by using monoclonal antibodies.
AB  - Five monoclonal antibodies (MAbs) were raised against the gag proteins of simian
      immunodeficiency virus (SIV) from African green monkey (SIVagmTYO-7). Two MAbs
      reacted with the matrix protein p17 and the other three with the core protein
      p24. Studies on the cross-reactivity of the MAbs revealed that the anti-p24 MAbs
      detected an epitope shared by the viruses belonging to the human immunodeficiency
      virus type 2 (HIV-2)/SIVmac group and SIVagmTYO-7 and SIVagmTYO-5. The anti-p17
      MAbs recognized an epitope present on all these viruses and on SIVagmTYO-1, HIV-1
      and SIVmnd. This finding demonstrates for the first time that the matrix protein,
      p17 or p18, respectively, of all nine HIV and SIV isolates tested in this study
      expresses at least one conserved immunogenic epitope recognized serologically. By
      using synthetic peptides, this epitope was identified at the N terminus of p17.
      Furthermore, this epitope was analysed by multiple sequence alignments of the
      peptide with homologous sequences of HIV and SIV p17.

PMID- 1383400
TI  - Genomic characterization and mutation rate of hepatitis C virus isolated from a
      patient who contracted hepatitis during an epidemic of non-A, non-B hepatitis in
      Japan.
AB  - To investigate the genomic characterization of hepatitis C virus (HCV) isolated
      from patient who contracted hepatitis during an epidemic of non-A, non-B (NANB)
      hepatitis in Shimizu city, Japan, we have cloned the nucleotide sequence of the
      viral genome (HCV-KF) spanning the structural domain. When compared to other
      previously reported HCV isolates, HCV-KF showed an overall identity at the amino
      acid level of 90.0 to 92.1% with Japanese isolates and 80.9 to 82.1% with
      American-like isolates. The HCV-KF genome displays an insertion of three
      nucleotides in-frame (corresponding to one amino acid) found at the junction
      between the E1 and E2/NS1 region. The mutation rate of the HCV-KF genome was
      assessed by comparing the nucleotide and deduced amino acid sequences of the
      viral RNA obtained from the serum of the original patient with viral sequences
      derived from the serum of a chimpanzee inoculated with the same serum 9 years
      previously. The substitution rate of the viral genome was estimated at 0.9 x 10(
      3) nucleotides per site per year for the HCV structural region. The highest
      mutation rate was found in the hypervariable region within the E2/NS1 domain. It
      is suggested that the outbreak in Shimizu city was caused by a strain of HCV
      closely related to the Japanese-like subgroup of isolates.

PMID- 1383401
TI  - Molecular cloning of a mink prion protein gene.
AB  - Transmissible mink encephalopathy (TME) is a rare disease which is presumably
      transmitted to ranch-raised mink from scrapie-infected sheep offal or bovine
      spongiform encephalopathy-infected cattle products. Although the infectious agent
      of TME has not been isolated, there is circumstantial evidence that TME is caused
      by prions. The experimental host range of TME includes sheep, cattle, monkeys and
      hamsters. However, TME has never been transmitted to mice. Since experiments in
      transgenic animals have shown that the prion protein (PrP) gene modulates the
      susceptibility, incubation time and neuropathology of prion-induced disease, we
      have started to analyse the mink PrP gene. PrP, as deduced from a genomic DNA
      sequence, consists of 257 amino acids and overall shows similarity of 84 to 90%
      with the sequences of the PrPs of other mammalian species. It remains to be
      determined whether these differences in the primary structure of PrP will explain
      the peculiar host range of TME.

PMID- 1383402
TI  - Heterogeneity of linear B cell epitopes of the measles virus fusion protein
      reacting with late convalescent sera.
AB  - B cell epitopes of the measles virus fusion protein were mapped, by reacting sera
      from late convalescent donors with synthetic overlapping pentadecapeptides,
      segments covering the whole F protein sequence. Unselected individual sera
      recognized 7 to 20% of the total sequence. Cumulation of the binding patterns of
      30 sera identified eight to 10 clusters of antibody-binding peptides spread over
      most of the sequence. The B cell epitopes included regions of transition between
      the more hydropathic (including the N-terminal end of the F1 and F2 protein) and
      hydrophilic sequences. When the regions of antibody binding were compared with
      the predicted secondary structure of the F protein, no detectable pattern became
      apparent. Exposed sequences as well as sequences hidden in the viral membrane or
      in the protein core of both the F1 and F2 polypeptides were recognized by the
      antibodies. The heterogeneity of the binding patterns was not merely dependent on
      the anti-measles virus titre. The importance of antibodies recognizing linear
      epitopes of the measles virus fusion protein for the immune protection is
      presently not known.

PMID- 1383403
TI  - Protective epitopes on the fusion protein of respiratory syncytial virus
      recognized by murine and bovine monoclonal antibodies.
AB  - The regions of the fusion protein of respiratory syncytial virus (RSV) that react
      with neutralizing, fusion-inhibiting and highly protective bovine and murine
      monoclonal antibodies (MAbs) were mapped by two methods: (i) competitive binding
      assays and (ii) production and analysis of antibody-escape mutants. Competitive
      binding assays with 16 murine and 10 bovine MAbs identified 11 antigenic sites on
      the fusion (F) protein, many of which overlapped extensively, and indicated that
      cattle, a natural host for RSV, and mice recognize similar epitopes. Neutralizing
      MAbs identified four sites, two of which were also fusion-inhibiting and highly
      protective in mice. The pattern of reactivity of antibody-escape mutants with the
      MAbs confirmed the mapping of the protective epitopes deduced from competitive
      binding assays. A comparison of the biological properties of MAbs to the F
      protein indicated that protection against RSV infection correlated with fusion
      inhibition rather than neutralization titre or complement-dependent lysis of
      virus-infected cells.

PMID- 1383405
TI  - Immunogenicity and vaccine efficacy of synthetic peptides containing Semliki
      Forest virus B and T cell epitopes.
AB  - A synthetic peptide that contains a Semliki Forest virus (SFV) B cell epitope,
      located at amino acid positions 240 to 255 of the E2 protein, and an SFV T helper
      (Th) cell epitope, located at positions 137 to 151 of the E2 protein, evoked high
      titres of SFV-reactive antibodies in H-2d mice. Although the peptide-induced
      antibodies did not neutralize SFV in vitro, 70 to 100% of the peptide-immunized
      mice were protected against SFV, even when viral challenge was presented 4 months
      after immunization. The protection could be transferred by anti-peptide serum,
      indicating that antibodies were responsible for the protection. When the Th cell
      epitope of this protective peptide was replaced by an influenza virus Th cell
      epitope or by another SFV Th cell epitope, the resulting peptides induced lower
      non-neutralizing SFV-reactive antibody titres and protected a correspondingly
      lower percentage of mice (50% and 30%, respectively). A peptide with the same Th
      cell epitope as the best protective peptide but with a less effective SFV B cell
      epitope protected only 33% of the mice. These results indicate that protection
      against SFV by a synthetic peptide is primarily dependent on its ability to
      induce adequate amounts of antibodies with relevant specificity and sufficient
      affinity; the ability to induce a relevant (SFV-specific) T memory response
      played only a minor role in protection.

PMID- 1383404
TI  - Characterization of two antigenic sites recognized by neutralizing monoclonal
      antibodies directed against the fusion glycoprotein of human respiratory
      syncytial virus.
AB  - Two antigenic sites recognized by neutralizing monoclonal antibodies (MAbs)
      directed against the fusion (F) glycoprotein of human respiratory syncytial virus
      were mapped on the primary structure of the protein by (i) the identification of
      amino acid substitutions selected in antibody-escape mutants and (ii) the
      reactivity of synthetic peptides with MAbs. The first site contained several
      overlapping epitopes which were located within the trypsin-resistant amino
      terminal third of the large F1 subunit. Only one of these epitopes was faithfully
      reproduced by a short synthetic peptide; the others might require specific local
      conformations to react with MAbs. The second antigenic site was located in a
      trypsin-sensitive domain of the F1 subunit towards the carboxy-terminal end of
      the cysteine-rich region. One of these epitopes was reproduced by synthetic
      peptides. In addition, mutagenized F protein with a substitution of serine for
      arginine at position 429 did not bind MAbs to the second site. These results are
      discussed in terms of F protein structure and the mechanisms of virus
      neutralization.

PMID- 1383407
TI  - Dissociable antiviral activities directed against cardioviruses are expressed in
      L cells treated with interferon.
AB  - Interferon (IFN) restricts a wide variety of viruses. To do so it elicits many
      antiviral pathways. For example, subclones of the same cell line with a reduced
      antiviral spectrum are thought to lack one or more antiviral pathways. Our line
      of L cells exhibits two distinct antiviral activities. The first delays the yield
      of both wild-type mengovirus (is+) and an IFN-sensitive mutant (is-1). The second
      specifically inhibits is-1 virus yields 100-fold. From these cells, a subclone
      was isolated which had lost the second antiviral activity (i.e. in these cells is
      1 virus acts like is+ virus). To see whether other cardioviruses are sensitive to
      these activities, two additional strains [m-mengovirus and encephalomyocarditis-R
      (EMC-R) virus] were tested in our subclones. Like is+ virus, m-mengovirus yields
      were delayed by IFN in both subclones; EMC-R virus behaved like is-1 virus in
      both cell lines. When actinomycin D was added at the time of infection, is-1
      virus was phenotypically reversed to is+ virus, but EMC-R virus was still
      inhibited. The 2-5A synthetase/RNase L pathway is expressed in both clones.
      Therefore, at least three antiviral activities against cardioviruses can be
      distinguished in IFN-treated L cells, and two of them appear not to involve the 2
      5A synthetase/RNase L pathway.

PMID- 1383406
TI  - The effects of poly(I).poly(C12U) and interferon on the multiplication of a
      mammalian type C retrovirus in human cells.
AB  - Poly(I).poly(C12U) or interferon treatment inhibited multiplication of the
      xenotropic baboon type C endogenous retrovirus M7 in chronically infected human
      AV3-M7 cells, as determined by a reverse transcriptase (RT) assay and electron
      microscopy. Furthermore, this polynucleotide induced 2'5' oligoadenylate (2'5'A)
      synthetase activity. In contrast to interferon (IFN), poly(I).poly(C12U) did not
      give rise to the appearance of a trapping phenomenon observable by electron
      microscopy. When AV3-M7 cells were treated simultaneously with poly(I).poly(C12U)
      and anti-IFN-beta/alpha antibodies, the induction of 2'5'A synthetase was
      abolished without any alteration of the inhibitory effect of RT activity. Taken
      together, these results suggest that different mechanisms are used by
      poly(I).poly(C12U) and IFN in blocking type C retrovirus multiplication.

PMID- 1383408
TI  - Vaccination by cholera toxin conjugated to a herpes simplex virus type 2
      glycoprotein D peptide.
AB  - Immunization of BALB/cJ mice with a peptide corresponding to residues 1 to 23 of
      glycoprotein D [gD(1-23)] from herpes simplex virus type 2 (HSV-2) elicits
      antibody responses which correlate with protection against lethal HSV-2
      infection. In the present study, we examined the ability of cholera toxin (CTX)
      to act as an immunogenic carrier for gD(1-23). The number of gD(1-23) residues
      conjugated to CTX affected its binding to GM1 ganglioside and physiological
      toxicity, both of which are factors affecting oral immunogenicity. The antibody
      response elicited after intraperitoneal (i.p.) immunization with the CTX-gD(1-23)
      conjugate was protective against a lethal i.p. challenge with HSV-2. In other
      experiments, mice were immunized i.p. on day 0 and subsequent immunizations
      conducted on days 14 and 28 were administered either intragastrically or
      intravaginally (i.vag.). Intraperitoneal priming followed by either i.p or
      intragastric boosting resulted in anti-HSV-2 antibodies in vaginal washings and
      in protection against a lethal i.vag. challenge with HSV-2. Intraperitoneal
      priming followed by i.vag. boosting did not elicit anti-HSV-2 antibodies in
      vaginal washings and did not protect mice against a lethal i.vag. challenge with
      HSV-2. These results suggest that CTX can act as a systemic and an oral delivery
      molecule for the covalently linked gD(1-23) peptide and that such conjugates can
      elicit protective immune responses against systemic and genital HSV-2 infection.

PMID- 1383409
TI  - Glycoprotein gp116 of human cytomegalovirus contains epitopes for strain-common
      and strain-specific antibodies.
AB  - Glycoprotein gp116 of human cytomegalovirus (HCMV) is a target for neutralizing
      antibodies. Gp116 is a component of the gCI complex which consists of gp58 and
      gp116. Like its homologue, glycoprotein B of herpes simplex virus type 1, gp116
      contains a highly antigenic region in the N-terminal part of the molecule,
      between amino acids 28 and 84. Prokaryotic expression plasmids and synthetic
      peptides were used to define binding sites for mouse and human monoclonal
      antibodies (MAbs) as well as HCMV convalescent sera. Site I, located between
      amino acids 68 and 77, contains an epitope recognized by the human MAb C23, which
      is capable of neutralizing HCMV independently of complement and the site is
      conserved between HCMV strains. Of HCMV-positive human sera, 53% recognized site
      I. Site II was mapped using mouse MAbs as well as human sera. It is located
      between residues 50 and 54, an area which is not conserved between strains AD169
      and Towne, the two laboratory strains of known sequence. Strain-specific
      antibodies were detected in 25% of human sera. Site II-specific antibodies,
      purified from human sera by affinity chromatography, were found to be incapable
      of neutralizing HCMV in tissue culture.

PMID- 1383410
TI  - Location of monoclonal antibody binding sites in the capsid protein of feline
      calicivirus.
AB  - We report the localization of three monoclonal antibody (MAb) binding sites in
      the capsid protein of feline calicivirus. Gene fragments were generated by
      restriction enzyme digestion or the polymerase chain reaction, and expressed as
      beta-galactosidase fusion proteins in Escherichia coli. These chimeric molecules
      were screened using three MAbs. A non-neutralizing MAb recognized a region within
      36 amino acids of the C terminus. Two neutralizing MAbs bound to a different
      region of 37 amino acids in the centre of the protein. Comparative sequence
      analysis shows this area to be the major variable region of the capsid protein.

PMID- 1383411
TI  - Highly conserved epitope domain in major core protein p24 is structurally similar
      among human, simian and feline immunodeficiency viruses.
AB  - Linear B cell epitopes were mapped on the major core protein p24 of human
      immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIVAGM) and
      feline immunodeficiency virus (FIV) using a fusion protein-based method and
      murine monoclonal antibodies reactive against the p24 antigens expressed on the
      surface of HIV-1- and FIV-infected cells. The results suggest that the sites
      identified here are encoded at similar positions in the three virus genomes and
      consist of highly conserved epitopes, which could exhibit immunodominance.

PMID- 1383412
TI  - Inhibition of viral replication by monoclonal antibodies directed against human
      immunodeficiency virus gp120.
AB  - Monoclonal antibodies (MAbs) were raised against the glycoprotein gp120 of human
      immunodeficiency virus type 1 (strain HTLV-IIIB). The reactivity of five selected
      MAbs was characterized in several tests: ELISA, immunostaining of Western blots,
      immunofluorescence, immunoprecipitation, immunoelectron microscopy, alkaline
      phosphatase-anti-alkaline phosphatase assay and neutralization. The binding
      region was delimited by sequential overlapping Escherichia coli fusion proteins
      of the gp120 sequence between amino acids (aa) 49 and 280. In the ELISA, when
      using sequential overlapping 15 aa peptides, the binding epitopes were localized
      between aa 64 and 78 for three MAbs and between aa 114 and 123 for the fourth
      Mab. The fifth Mab showed multiple reactions with different peptides possibly
      indicating a reaction with a discontinuous epitope. In virus growth inhibition
      assays, all five MAbs inhibited the spread of HIV-1 infection in cell cultures
      after a single or repeated treatment at a concentration of 63 micrograms/ml of
      the purified MAbs. All MAbs showed low but significant neutralizing activity at
      concentrations of 100 micrograms/ml.

PMID- 1383413
TI  - Mapping of sequential epitopes recognized by monoclonal antibodies on the bovine
      leukaemia virus external glycoproteins expressed in Escherichia coli by means of
      antipeptide antibodies.
AB  - A lambda gt11 cDNA library prepared from bovine leukaemia virus (BLV)-producing
      ovine cells was screened with a cocktail of anti-BLV gp51 monoclonal antibodies
      (MAbs). Four recombinant phages with inserts of about 2-5 kbp were isolated. One,
      lambda BLV-gp51-1, was sequenced and shown to encode the C-terminal part of gp51
      and all of gp30. This insert was subcloned into pEV-vrf1 and expressed in
      Escherichia coli N-4830-1 cells. The BLV product and a series of antipeptide
      antibodies were used to localize the sequential epitopes defined on BLV envelope
      glycoprotein gp51 by their reactivity with MAbs. Epitope B was localized to amino
      acids 180 to 205, B' to residues 195 to 205, D and D' to residues 218 to 237, and
      A to amino acids 249 to 260. All the mapped sequential epitopes were localized in
      the C-terminal half of BLV gp51. The results of epitope mapping with bacterially
      produced gp51 confirm the map obtained using native viral glycoprotein.

PMID- 1383414
TI  - A microtitre format point mutation assay: application to the detection of drug
      resistance in human immunodeficiency virus type-1 infected patients treated with
      zidovudine.
AB  - An assay for the analysis of point mutations in DNA fragments amplified by the
      polymerase chain reaction is described. The method was applied to the analysis of
      mutations leading to single amino acid changes in the reverse transcriptase gene
      of human immunodeficiency virus type-1 that are associated with decreased
      sensitivity of the virus to the effects of the nucleoside analogue zidovudine.
      The assay uses a microtitre format allowing large numbers of clinical samples to
      be analysed, and is a quantitative assay giving information on the relative
      proportions of wild-type and mutant sequence at the point being analysed. The
      analysis of mutations in codons 67, 70, 215, and 219 of the RT gene in samples
      taken at various time points after the commencement of zidovudine therapy shows a
      high variability in the rate at which these mutations arise and in the
      proportions of wild-type and mutant sequences observed. The method we describe
      has wide application to the analysis of other point mutations in clinical or
      research studies.

PMID- 1383415
TI  - Hepatitis B surface antigen particles of subtypes adw and adr, and compound
      subtype (adwr) in symptom-free carriers in Japan.
AB  - Of sera from 1,878 Japanese blood donors who carried hepatitis B surface antigen
      (HBsAg), 420 were subtyped as adw (22.4%) and 1,443 as adr (76.8%); only 15
      (0.8%) contained HBsAg of subtype ayw or ayr. Sera with HBsAg/adr had higher
      HBsAg titres than those with HBsAg/adw (geometric mean of haemagglutination
      titre: 10.1 +/- 2.4 vs. 9.7 +/- 2.4, p less than 0.01), and a higher prevalence
      of hepatitis B e antigen (24% vs. 13%, p less than 0.001). Carriers of HBsAg/adr
      progressively predominated over those of HBsAg/adw with increasing age. Of sera
      from 1,863 carriers of HBsAg/adw or HBsAg/adr, 182 (9.8%) contained HBsAg
      particles with both subtypic determinants in the w/r allele. The presence of w
      and r determinants on the same particles was ascertained by sandwiching them
      between monoclonal antibody with the specificity for w and that with the
      specificity for r. HBsAg particles of compound subtype (adwr) were found more
      often in sera with hepatitis B e antigen than those without it (145/403 [36.0%]
      vs. 37/1,460 [2.5%], p less than 0.001). Sera with HBsAg/adwr particles had HBsAg
      titres higher than those without them (12.4 +/- 1.9 vs. 9.7 +/- 2.3, p less than
      0.001). HBsAg/adwr particles arise from phenotypic mixing of the S-gene product
      of wild-type virus and that of mutants with point mutations for subtypic changes.
      The results obtained indicated that HBV strains of subtype adr have a higher
      replicative activity than those of adw, and suggested that mutations in the S
      gene for subtypic changes would be associated with an active replication of
      hepatitis B virus.

PMID- 1383416
TI  - Persistence of hepatitis B virus DNA after reduction of viral replication in
      serum and liver.
AB  - Liver and serum samples from 67 children with hepatitis B chronic infection,
      whether or not treated with recombinant interferon, were analyzed for the
      presence of hepatitis B virus DNA. After follow-up, 44/67 (66%) still had serum
      and liver viral DNA; 23/67 (34%) were negative for serum hepatitis B virus DNA.
      Of the 23 children in the latter group, liver biopsy was available in 21 and
      viral DNA was not detected by Southern-blot in 20. In the remaining patient,
      viral DNA was in an episomal nonreplicative form. Polymerase chain reaction was
      performed in the 21 serum samples negative for viral DNA by conventional
      techniques and in the 21 liver samples (20 negative for hepatitis B virus DNA and
      1 with episomal nonreplicative form). All liver samples resulted in a positive
      reaction to viral DNA by this technique. Serum viral DNA by polymerase chain
      reaction was detected in 15/21 (71%) of these patients. The mean of alanine
      aminotransferase values was similar in patients with or without hepatitis B virus
      DNA in serum by polymerase chain reaction. In summary, in the majority of the
      patients who respond to the therapy, there is a persistence of viral replication
      detected by polymerase chain reaction. This fact explains the persistence of
      serum HBsAg in these patients. However, more studies are necessary to determine
      the meaning of the presence of hepatitis B virus DNA that is only detectable by
      polymerase chain reaction.

PMID- 1383417
TI  - Effects of transforming growth factor-beta 1 against the inhibitory action of
      interferon on DNA synthesis and viral replication in hepatitis B virus DNA
      transfected cell.
AB  - Studies were undertaken to examine the effects of recombinant human transforming
      growth factor beta 1 (TGF-beta 1) on DNA synthesis and antiviral actions of
      interferons (IFNs) in HepG2 cell, a hepatoma cell line, transfected with
      hepatitis B virus (HBV) DNA. The inhibitory effects of IFN-alpha and -gamma on
      DNA synthesis of HepG2 cells were enhanced in a dose-dependent manner by a
      simultaneous addition of TGF-beta. The degree of suppression by the reagents was
      greater in HBV-nontransfected cells than in transfected cells. Inhibition of DNA
      synthesis was not due to direct cytotoxic effects of the additives, since the
      viability of HepG2 cells was comparable in the control and treated cultures as
      determined by trypan blue exclusion. Treatment of HBV DNA-transfected HepG2 cells
      with IFNs resulted in decrease in production of HB surface and e antigens, and in
      the level of HBV DNA, but TGF-beta reversed the IFN-induced antiviral state in
      HBV DNA-transfected HepG2 cells. TGF-beta had no direct effect on HBV
      replication. These results indicate that rTGF-beta 1 exerts a differential effect
      against the inhibitory actions of IFN on DNA synthesis and viral replication in
      HepG2 cells.

PMID- 1383418
TI  - Detection of St. Louis encephalitis virus in mosquitoes by use of the polymerase
      chain reaction.
AB  - We recently developed an assay using the polymerase chain reaction (PCR) for the
      specific detection of St. Louis encephalitis (SLE) virus RNA. This assay was
      tested in a blind study on 7 samples of pooled mosquitoes (50 mosquitoes/pool)
      which were also characterized for SLE virus by plaque assay in Vero cell culture.
      One sample was positive for the SLE virus as determined by both the PCR assay and
      a combination of the plaque assay and the indirect fluorescent antibody assay.
      The remaining 6 samples were negative for the presence of SLE virus as determined
      by both methods. These data indicate that this PCR assay can be used to monitor
      for the presence of SLE virus in pools of homogenized mosquitoes. This approach
      could provide early data on which to base disease control decisions.

PMID- 1383419
TI  - Two pathways of cyclic GMP production through glutamate receptor-mediated nitric
      oxide synthesis.
AB  - The selective agonists for the metabotropic glutamate receptor and the ionotropic
      non-N-methyl-D-aspartate (NMDA) glutamate receptor, (+/-)-1-aminocyclopentane
      trans-1,3-dicarboxylic acid (ACPD) and (R,S)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA), respectively, increased the cyclic GMP
      (cGMP) content in cerebellar slices prepared from adult rats. The ACPD-induced
      rise in cGMP level was blocked by compounds known to antagonize metabotropic
      glutamate receptors, such as DL-2-amino-3-phosphonopropionic acid and L-2-amino-4
      phosphonobutyric acid, but not by ionotropic glutamate receptor antagonists, D-2
      amino-5-phosphonovaleric acid and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX),
      whereas the AMPA-induced rise in cGMP level was suppressed by CNQX. Both rises in
      cGMP level involved nitric oxide synthase (NOS), because NG-methyl-L-arginine
      (NMLA), an inhibitor of NOS, blocked both cGMP level rises, and excess L-arginine
      reversed the effect of NMLA. After lithium chloride treatment, which could
      exhaust phosphatidylinositol phosphates, ACPD no longer increased cGMP levels,
      whereas AMPA was still effective. In a calcium-free medium, ACPD still induced a
      rise in cGMP level, whereas AMPA did not. When the molecular layer was isolated
      to determine the cGMP content separately from that in the rest of the cerebellar
      cortex, it was found that ACPD raised the cGMP level mainly in the molecular
      layer, whereas AMPA raised it in both sections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383420
TI  - Distribution of calcitonin gene-related peptide in rat and rabbit spinal cords:
      effect of intrathecal 5,7-dihydroxytryptamine.
AB  - Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) was measured in
      selected regions of the cervical, thoracic, and lumbar spinal cord of untreated
      rabbits and, following intrathecal injection of the serotonergic neurotoxin 5,7
      dihydroxytryptamine (5,7-DHT), in the thoracolumbar cord in rats using a sheep
      antiserum raised against tyrosine0 calcitonin gene-related peptide28-37. In the
      cervical, thoracic, and lumbar segments of the rabbit spinal cord, CGRP-LI levels
      were 15-50-fold higher in the dorsal than in the ventral grey region in the same
      segment. The only segmental variation in CGRP-LI levels was in the dorsal white
      region, where levels in the thoracic cord were lower than those in cervical or
      lumbar segments. Within individual spinal segments, the pattern of distribution
      of CGRP-LI in the rabbit spinal cord was analogous to that in other species
      previously examined, including rat, human, and cat spinal cord. Intrathecal
      injection of 5,7-DHT, which caused 85-91% depletion of 5-hydroxytryptamine and 5
      hydroxyindoleacetic acid from the thoracolumbar ventral spinal cord, did not
      affect choline acetyltransferase activity, which is colocalized with CGRP in
      motoneurones in this spinal cord region. In contrast, intrathecal 5,7-DHT
      produced a threefold increase in CGRP-LI in the ventral thoracolumbar cord,
      suggesting that spinal motoneurones selectively increase production of CGRP 10
      days after neurotoxin-induced denervation of bulbospinal raphe neuronal input.

PMID- 1383421
TI  - Expression of nerve growth factor and nerve growth factor receptor genes in human
      tissues and in prostatic adenocarcinoma cell lines.
AB  - Nerve growth factor (NGF) mRNAs were detected and quantified in a variety of
      normal and neoplastic human tissues by northern blot hybridization. Human heart
      contained the highest NGF mRNA levels, whereas lower but comparable levels were
      found in the placenta, prostate, and kidney. All tissues examined coexpressed the
      low-affinity NGF receptor (LNGFR), whereas none of these tissues expressed the
      high-affinity NGF receptor encoded by the trk protooncogene. The widespread
      distribution of the LNGFR suggests that it plays a role in the regulation of
      normal cell growth. No overexpression of NGF or LNGFR mRNA was detected in
      neoplastic tissues, whereas LNGFR-like immunoreactivity was localized outside of
      tumor cells. Transforming growth factor-alpha and protooncogene c-fos expression
      in these tissues did not show a systematic correlation with NGF/LNGFR expression.
      Furthermore, regulation of the human NGF gene was studied in DU145 cells, a
      prostatic adenocarcinoma cell line that synthesizes significant NGF mRNA levels.
      Serum induced, whereas dexamethasone inhibited, NGF mRNA synthesis in these
      cells. Serum induction was preceded by a rapid and transient activation of the c
      fos protooncogene.

PMID- 1383422
TI  - An antibody specific for component 8 of myelin basic protein from normal brain
      reacts strongly with component 8 from multiple sclerosis brain.
AB  - Myelin basic protein (MBP) consists of several components or charge isomers (C-1
      through C-8) generated by one or a combination of posttranslational
      modifications. One of these, C-8, has been shown to contain citrulline (Cit) at
      defined sites formed by deimination of six arginyl residues. This unusual
      modification has allowed us to raise antibodies specific for this charge isomer
      only. To do this, a synthetic peptide, Gly-Cit-Cit-Cit-Cit, was coupled to
      keyhole limpet hemocyanin and injected into rabbits. The antibodies so generated
      reacted only with C-8 and not with any of the other charge isomers. A second
      antibody fraction was raised against the synthetic peptide ACitHGFLPCitHR
      naturally occurring between residues 24 and 33 of C-8 (all other charge isomers
      contain R instead of Cit at positions 25 and 31). These antibodies preferred C-8
      but reacted with the other charge isomers, to the extent of approximately 25-30%
      of the reactivity shown with C-8. In studies with C-8 from multiple sclerosis
      (MS) MBP, much greater reactivity was obtained with these antibodies when
      compared with their reactivity with C-8 from normal MBP. Because the total number
      of Cit residues in C-8 from MS and normal MBP is the same, the difference in
      reactivity may be related to structural factors. The antibodies raised with the
      tetra-Cit peptide were reacted with three pairs of synthetic peptides:
      24ARHGFLPRHR33 and ACitHGFLPCitHR; 120GQRPGFGYGGRAS132 and GQCitPGFGYGGCitAS; and
      157GGRDSRSGSPMARR170 and GGCitDSRSGSPMACitR. They reacted only with the Cit
      containing peptides in the order 157-170 greater than 120-130 greater than 24
      33.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383423
TI  - The basic protein of CNS myelin: its structure and ligand binding.
AB  - Consideration of the evidence presented in this review leads to the following
      conclusions: (a) Isolated MBP in aqueous solution has little ordered secondary or
      tertiary structure. (b) In this state, the protein can associate with a wide
      range of hydrophobic and amphiphilic compounds, these interactions involving
      limited sections of the protein. (c) The strength of binding to bilayers and the
      accompanying conformational changes in the protein are greatest for systems
      containing acidic lipids, presumably because of the involvement of ionic
      interactions. (d) When bound to bilayers of acidic lipids, MBP will have
      substantially more ordered secondary structure than it manifests in aqueous
      solution, and it is likely to be oligomeric (possibly hexameric). (e) MBP does
      affect the organization of lipid aggregates. It influences strongly the
      separation of bilayers in multilayers of purified lipids, and at present this
      must be viewed as its prime role within myelin. The greatest impediment to our
      understanding of MBP is the lack of an assayable biological activity. In contrast
      to the situation with enzymes, for example, we have no functional test for
      changes in protein structure or changes accompanying interactions with other
      molecules. Current evidence suggests that the protein has a structural role
      within myelin and that its own three-dimensional structure is strongly dependent
      on the molecules with which it is associated. If this picture is correct, studies
      of the isolated protein or of the protein in reconstituted lipid systems may
      yield, at best, a rough guide to the structure within its biological environment.
      Further clarification of the structure and function of MBP may have to await
      development of more powerful techniques for studying proteins bound to large
      molecular aggregates, such as lipid bilayers. The paucity of generally applicable
      methods is reflected in the fact that even low resolution structures are known
      for only a handful of intrinsic membrane proteins, and even more limited
      information exists for proteins associated with membrane surfaces. However, the
      increasing use of a combination of electron microscopy and diffraction on two
      dimensional arrays of proteins formed on lipid bilayers (Henderson et al., 1990)
      offers the hope that it may not be too long before it will be possible to study
      at moderate resolution the three-dimensional structure of MBP bound to a lipid
      membrane.

PMID- 1383424
TI  - Isolated bovine spinal motoneurons have specific ganglioside antigens recognized
      by sera from patients with motor neuron disease and motor neuropathy.
AB  - The gangliosides GM1 and GD1b have recently been reported to be potential target
      antigens in human motor neuron disease (MND) or motor neuropathy. The mechanism
      for selective motoneuron and motor nerve impairment by the antibodies directed
      against these gangliosides, however, is not fully understood. We recently
      investigated the ganglioside composition of isolated bovine spinal motoneurons
      and found that the ganglioside pattern of the isolated motoneurons was extremely
      complex. GM1, GD1a, GD1b, and GT1b, which are major ganglioside components of CNS
      tissues, were only minor species in motoneurons. Among the various ganglioside
      species in motoneurons, several were immunoreactive to sera from patients with
      MND and motor neuropathy. One of these gangliosides was purified from bovine
      spinal cord and characterized as N-glycolylneuraminic acid-containing GM1
      [GM1(NeuGc)] by compositional analysis, fast atom bombardment mass spectra, and
      the use of specific antibodies. Among seven sera with anti-GM1 antibody
      activities, five sera reacted with GM1(NeuGc) and two did not. Two other
      gangliosides, which were recognized by another patient's serum, appeared to be
      specific for motoneurons. We conclude that motoneurons contained, in addition to
      the known ganglioside antigens GM1 and GD1b, other specific ganglioside antigens
      that could be recognized by sera from patients with MND and motor neuropathy.

PMID- 1383426
TI  - Triiodothyronine has diverse and multiple stimulating effects on expression of
      the major myelin protein genes.
AB  - If the importance of triiodothyronine (T3) on brain development including
      myelinogenesis has long been recognized, its mechanism of action at the gene
      level is still not fully elucidated. We studied the effect of T3 on the
      expression of myelin protein genes in aggregating brain cell cultures. T3
      increases the concentrations of mRNA transcribed from the following four myelin
      protein genes: myelin basic protein (Mbp), myelin-associated glycoprotein (Mag),
      proteolipid protein (Plp), and 2',3'-cyclic nucleotide 3'-phosphodiesterase
      (Cnp). T3 is not only a triggering signal for oligodendrocyte differentiation,
      but it has continuous stimulatory effects on myelin gene expression.
      Transcription in isolated nuclei experiments shows that T3 increases Mag and Cnp
      transcription rates. After inhibiting transcription with actinomycin D, we
      measured the half-lives of specific mRNAs. Our results show that T3 increases the
      stability of mRNA for myelin basic protein, and probably proteolipid protein. In
      vitro translation followed by myelin basic protein-specific immunoprecipitation
      showed a direct stimulatory effect of T3 on myelin basic protein mRNA
      translation. Moreover, this stimulation was higher when the mRNA was already
      stabilized in culture, indicating that stabilization is achieved through mRNA
      structural modifications. These results demonstrate the diverse and multiple
      mechanisms of T3 stimulation of myelin protein genes.

PMID- 1383425
TI  - Hypoxia induces synthesis of a novel 22-kDa protein in neonatal rat
      oligodendrocytes.
AB  - Neonatal (3-day-old) rat oligodendrocytes grown in monolayer culture and exposed
      to increasingly hypoxic culture conditions showed a dramatic reduction in myelin
      basic protein synthesis but no significant inhibition of Tran35S-label
      incorporation into oligodendrocyte proteins in general or into structural
      proteins such as actin. However, there was a dramatic increase in synthesis of a
      novel 22-kDa protein. Reoxygenation of cultures reversed the synthesis of the 22
      kDa protein, and thiol and calpain protease inhibitors (EP-459 and leupeptin) did
      not prevent synthesis of the protein, suggesting that it did not result from
      proteolysis. The 22-kDa protein (which we have called hypoxin) was
      coimmunoprecipitated by a polyclonal antibody to actin but did not react with the
      anti-actin antibody on western blots. The synthesis of hypoxin accounted for up
      to 50% of the Tran35S-label incorporated into immunoprecipitated protein,
      suggesting that it plays a major role in the cell's response to hypoxia.
      Subcellular fractionation revealed that the 22-kDa protein was largely associated
      with the cytosolic/cytoskeletal compartment. However, it is unlikely to be one of
      the cytoskeleton-associated Rho or Rac low-molecular-mass (20-24 kDa) GTP-binding
      proteins because it did not bind [alpha-32P]GTP on western blots.
      Oligodendrocytes did not synthesize a 22-kDa protein in response to heat shock
      but did synthesize the typical 70- and 90-kDa heat-shock proteins.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1383428
TI  - Formation and clearance of interstitial metabolites of dopamine and serotonin in
      the rat striatum: an in vivo microdialysis study.
AB  - In vivo microdialysis was employed in order to characterize the steady-state
      kinetics of the turnover of specific dopamine and serotonin metabolites in the
      rat striatum 48 h after surgery. Inhibitors of monoamine oxidase (MAO; pargyline)
      and catechol-O-methyltransferase (COMT; Ro 40-7592) were administered, either
      separately or in conjunction, at doses sufficient to block these enzymes in the
      CNS. In some experiments, the acid metabolite carrier was blocked with
      probenecid. Temporal changes were then observed in the efflux of interstitial
      dopamine, 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC),
      homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). The fractional
      rate constants for the accumulation or disappearance of the metabolites could be
      determined after pharmacological blockade of catabolic enzymes or the acid
      metabolite carrier. Interstitial 5-HIAA was found to be cleared with a half-life
      of approximately 2 h. After blockade of either MAO or COMT, HVA disappeared with
      a half-life of 17 min. Experiments employing probenecid suggested that some of
      the interstitial HVA was cleared by the acid metabolite carrier, the remainder
      being cleared by a probenecid-insensitive process, possibly conjugation. After
      MAO inhibition, DOPAC disappeared with an apparent half-life of 11.3 min. The
      rate of 3-MT accumulation after pargyline indicated that the majority of
      interstitial HVA (> 95%) is formed from DOPAC rather than 3-MT. The formation of
      3-MT from interstitial dopamine, calculated from the accumulation rate of 3-MT
      after pargyline, appeared to follow first-order kinetics (k = 0.1 min-1).

PMID- 1383427
TI  - Differences in the in vitro and in vivo 5-hydroxytryptamine extraction
      performance among three common microdialysis membranes.
AB  - The present study summarizes the results of an in vitro and in vivo comparison of
      the apparent 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 3,4
      dihydroxyphenylacetic acid dialysis performance of three types of membrane
      frequently used in intracerebral microdialysis experiments. The dialysis fiber
      types examined were a regenerated cellulose Cuprophan (GF), a proprietary
      polycarbonate ether (CMA), and a polyacrylonitrile/sodium methallylsulfonate
      copolymer (HOSPAL). The experiments unexpectedly revealed that the HOSPAL
      membrane-equipped probes displayed clearly aberrant 5-HT diffusion dynamics
      compared with GF and CMA probes, demonstrable not only in vitro, but also in in
      vivo experiments. In vitro, the GF and CMA membrane-equipped probes exhibited
      maximum relative recovery for 5-HT already in the first 20-min sample, whereas
      the 5-HT recovery of HOSPAL probes increased in a very slow and protracted manner
      over a period of a little less than 2 h. The GF and CMA probes further displayed
      an immediate washout of 5-HT when the probes were subsequently transferred to
      artificial CSF only-containing medium (no 5-HT), whereas approximately 2 h was
      required to yield near-total extinction of dialysate 5-HT with the standard
      HOSPAL probes. In vivo, the rat ventral hippocampal dialysate 5-HT output
      responses to K+ (100 mM) infusion, to Ca2+ omission, and to systemic 8-hydroxy-2
      (di-n-propylamino)tetralin injection were all markedly retarded and blunted when
      HOSPAL instead of GF membrane-equipped probes were used. However, the 5
      hydroxyindoleacetic acid and 3,4-dihydroxyphenylacetic acid extraction in vitro
      and in vivo were comparable using either of the membrane types.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1383429
TI  - Expression of an inwardly rectifying potassium channel in Xenopus oocytes.
AB  - The murine macrophage-like cell line J774.1 was used as a source of mRNA for the
      expression of inwardly rectifying potassium channels in Xenopus oocytes. RNA was
      isolated, poly(A)(+)-selected, and size-fractionated by sucrose density gradient
      centrifugation. Oocytes injected with J774.1 RNA expressed large-amplitude
      current (0.9 +/- 0.07 microA; mean +/- SEM, n = 31) at -100 mV in 96 mM
      extracellular K+ showing prominent inward rectification. The inwardly rectifying
      currents were most strongly expressed by an mRNA size class of 4-5 kb. The
      expressed current displayed selectivity, conductance, and rectification
      properties of inwardly rectifying potassium channels in their native membranes.
      The current was potassium selective and was specifically blocked by Ba2+. The
      conductance and the voltage dependence of the current rectification depended on
      the extracellular potassium concentration, with the midpoint in peak conductance
      following the potassium equilibrium potential. This high level of expression of
      inward rectifier current and the absence of other expressed currents suggest that
      J774.1 mRNA represents an excellent starting material for expression cloning of
      the inward rectifier potassium channel cDNA.

PMID- 1383430
TI  - Functional reconstitution of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate
      (AMPA) receptors from rat brain.
AB  - Glutamate receptors belonging to the subclass specifically activated by alpha
      amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) were solubilized from
      rat forebrain membranes with Triton X-100 and partially purified through a series
      of three chromatographic steps. Specific [3H]AMPA binding increased 30-60-fold
      during the isolation procedure. A protein band recognized by antibodies against
      specific amino acid sequences of the glutamate receptor-A subunit was enriched
      with each purification step; the molecular mass of this band (105 kDa)
      corresponded to that of cloned AMPA receptor subunits. Photoaffinity labeling of
      forebrain membranes with 6-cyano-7-[3H]nitroquinoxaline-2,3-dione, a specific
      antagonist of the AMPA receptor, labeled a single band that comigrated with the
      immunolabeled protein. On reconstitution of the partially purified material into
      bilayer patches, single-channel current fluctuations were elicited by 300 nM AMPA
      and blocked by 1 microM 6,7-dinitroquinoxaline-2,3-dione.

PMID- 1383431
TI  - Evidence for the transport of opsin in the connecting cilium and basal rod outer
      segment in rat retina: rapid-freeze, deep-etch and horseradish peroxidase
      labelling studies.
AB  - In order to clarify the pathway of opsin transport in the connecting cilium and
      basal rod outer segment, we examined rat rod cells by a rapid-freeze and deep
      etch technique and also examined the uptake of horseradish peroxidase into
      isolated retina. The distribution of intramembrane particles on the P-face of the
      cilium indicated that the ciliary plasma membrane has similar opsin content to
      the basal rod outer segment plasma membrane. Dilated cisternae were detected
      below the stack of disk membranes at the basal rod outer segment in fresh retina.
      The fine structure of the P-face and true surface of these cisternae was
      identical to that of the disk membrane. Uptake of horseradish peroxidase was
      detected in the cisternae or in both cisternae and most basal disk, indicating
      that the cisternae are formed prior to the disk membrane. In the distal part of
      connecting cilium, we found axially oriented infoldings on the P-face of the
      plasma membrane, and subplasmalemmal tubules or cisternae adjacent and parallel
      to them. Such subplasmalemmal membranes were labeled by exogenous horseradish
      peroxidase, suggesting that the infoldings are invaginating plasma membrane.
      These results may indicate that opsin molecules are conveyed on the ciliary
      plasma membrane, and that this opsin-rich plasma membrane is internalized in the
      distal connecting cilium to form dilated cisternae, which subsequently change to
      the disk membranes.

PMID- 1383432
TI  - Astroglial membrane structure is affected by agents that raise cyclic AMP and by
      phosphatidylcholine phospholipase C.
AB  - The role of signal transduction mechanisms in the production of the
      characteristic orthogonal arrays of particle assemblies in the astroglial plasma
      membrane was investigated in vitro by freeze-fracture electron microscopy. Agents
      which raise cellular cAMP levels and subsequently activate protein kinase A, such
      as forskolin (50 microM), isoproterenol (10 microM) and 8-bromo-cAMP (1 mM),
      increased the density, the number of assemblies per unit area of cleaved cell
      membrane, and the frequency of astrocytes with assemblies. Agents that lead to
      the activation of protein kinase C, such as phorbol 12,13-myristate acetate (at
      50 nM) and choline-dependent phospholipase C (at 0.01-0.1 U ml-1), did not affect
      the assembly concentration. Thus, protein kinase A but not protein kinase C
      appears to be involved in the production of assemblies or their insertion into
      the astroglial plasma membrane. Although choline-dependent phospholipase C did
      not affect the astroglial assemblies, it caused the non-assembly, background
      particles to aggregate. A choline-dependent phospholipase C from a different
      source (B. cereus) was also active though at a higher concentration.
      Phospholipases of different specificities, such as phospholipase A2,
      phospholipase D or inositol-dependent phospholipase C were inactive over a wide
      range of concentrations. Two other astroglia derived cells, Muller cells and
      cells of the C6 glioma cell line, were also similarly affected by choline
      dependent phospholipase C, while six other cells types including neurons,
      endothelial cells and fibroblasts were unaffected. It appears that
      phosphatidylcholine plays a significant role in determining the membrane
      structure of astrocytes. In a search for a means of isolating the assemblies, the
      binding of three lectins: ConA, WGA and PNA, conjugated to gold, was tested by
      label-fracture to ascertain whether the assemblies have an external
      oligosaccharide component. None of the lectins bound specifically to assemblies.

PMID- 1383433
TI  - Improved palliation of cerebral metastases in epithelial ovarian cancer using a
      combined modality approach including radiation therapy, chemotherapy, and
      surgery.
AB  - PURPOSE: Recent reports suggest an increasing incidence of CNS metastases in
      patients with ovarian cancer. We reviewed our experience in the management of
      brain metastases from ovarian carcinoma and merged our results with those of
      several other series reported in the literature to determine prognostic factors
      and the role of chemotherapy, radiation therapy, and surgery. PATIENTS AND
      METHODS: From 1977 to 1990, 15 of 795 patients who were treated for epithelial
      ovarian cancer at Duke University developed brain metastases. Fourteen of the
      patients were treated for their brain metastases; this included radiation therapy
      (RT; four), surgery and RT (one), RT and systemic chemotherapy (six), and all
      three treatment modalities (three). A meta-analysis was performed that combined
      the data from the current series with those of several recent clinical series
      that reviewed patients with brain metastases from ovarian carcinoma (67 patients
      total) to elucidate the impact of treatment and extent of disease on survival.
      RESULTS: In the current series, median survival (MS) after the diagnosis of brain
      metastases was 9 months. For the combined series, MS was 5 months. Thirteen
      patients who were treated with whole-brain RT and systemic chemotherapy (MS, 7
      months), 10 patients who were treated with RT and surgery (MS, 10 months), and
      nine patients who were treated with all three modalities (MS, 16.5 months) had
      significantly longer survival than 19 patients who were treated with RT alone
      (MS, 3 months) (P = .05, P = .01, and P < .001, respectively). In a multivariate
      analysis, the only variable that provided prognostic information was treatment,
      namely the addition of systemic chemotherapy or surgery to RT for the treatment
      of brain metastases. CONCLUSION: Multimodal treatment of patients with brain
      metastases from ovarian cancer can result in significant palliation.

PMID- 1383434
TI  - Low-dose radiation therapy and reduced chemotherapy in childhood Hodgkin's
      disease: the experience of the French Society of Pediatric Oncology.
AB  - PURPOSE: With the aim of decreasing undesirable side effects of therapy, we
      investigated the reduction of both chemotherapy and radiation therapy (RT) in
      children with Hodgkin's disease, and compared Adriamycin (doxorubicin; Farmitalia
      Carlo Erba, Rueil-Malmaison, France), bleomycin, vinblastine, and dacarbazine
      (ABVD) alone to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)
      and ABVD in favorable cases and assessed the effectiveness of low-dose RT (20 Gy)
      after good response to chemotherapy. PATIENTS AND METHODS: A French national
      study began in 1982 that included 238 pediatric patients with Hodgkin's disease.
      Initial staging was clinical and without laparotomy. In patients with localized
      disease (IA-IIA), an equivalence trial compared the effectiveness of four cycles
      of ABVD with two cycles of ABVD that were alternated with two cycles of MOPP.
      Patients with more advanced disease (IB-IIB-III-IV) received three courses of
      MOPP that was alternated with three courses of ABVD. All of the patients who
      achieved a good remission after chemotherapy were administered 20 Gy RT, which
      was limited to the initially involved areas for localized disease, and
      encompassed the paraaortic nodes and the spleen as well for more advanced stages.
      When a good remission was not obtained, 40 Gy RT was administered. RESULTS: At
      the completion of chemotherapy, 227 patients (97%) were considered good
      responders, whereas 11 did not achieve a good remission. With a median follow-up
      of 6 years, the 6-year actuarial survival was 92% and the disease-free survival
      was 86%. The relapse-free survival in favorable stages was 90% in the ABVD arm
      and was 87% in the MOPP and ABVD arm. In June 1987, inclusion of stage IV
      patients was discontinued because of poor results. CONCLUSIONS: Present findings
      indicate that (1) in favorable stages, ABVD alone and alternating MOPP and ABVD
      are equivalent, and (2) chemotherapy followed by 20 Gy RT represents a valid
      therapeutic approach in the vast majority of children with Hodgkin's disease.

PMID- 1383435
TI  - Bone marrow transplantation prolongs survival after relapse in aggressive
      lymphoma patients treated with the LNH-84 regimen.
AB  - PURPOSE: Of the 737 patients with aggressive lymphoma who were treated with the
      LNH-84 regimen, 244 with progressive disease after complete remission or partial
      response were analyzed retrospectively to determine the influence of intensive
      chemotherapy with bone marrow transplantation (BMT) on survival. PATIENTS AND
      METHODS: Forty-four patients were treated with salvage chemotherapy, followed by
      autologous bone marrow transplantation (ABMT) in 40 and allogeneic BMT in four.
      The other 200 patients were treated with chemotherapy only. RESULTS: Salvage
      treatment produced an objective response in 57% of the patients; 23% achieved a
      second complete remission. Median overall survival was longer for patients who
      were treated with ABMT than for those who were treated with chemotherapy only
      (12.4 v 6.7 months), as was median freedom from progression (FFP) survival (7.7 v
      4 months). In multiparametric analysis, ABMT and normal initial lactic
      dehydrogenase (LDH) level were the primary parameters associated with longer
      survival. This is also true when (1) only patients younger than 60 years of age,
      (2) only patients who responded to salvage regimen, or (3) only patients with
      both conditions were included in the analysis. Patients who were not transplanted
      had a 1.69 to 2.26 relative risk of dying from their disease compared with those
      who were treated with intensive chemotherapy plus ABMT. CONCLUSION: This study
      produced more evidence of the favorable impact of intensive chemotherapy with
      bone marrow rescue on survival in lymphoma patients who had relapsed.

PMID- 1383436
TI  - Phase II study of estramustine and vinblastine, two microtubule inhibitors, in
      hormone-refractory prostate cancer.
AB  - PURPOSE: Estramustine phosphate (EMP) and vinblastine are two microtubule
      inhibitors with distinct molecular targets and at least additive antimicrotubule
      effects in vitro. Their modest single-agent activities in hormone-refractory
      prostate cancer, nonoverlapping toxicities, and lack of cross-resistance prompted
      a phase II trial in hormone-refractory prostate cancer. PATIENTS AND METHODS:
      Thirty-six assessable patients at the Fox Chase Cancer Center and seven Fox Chase
      Cancer Center Network institutions were treated with oral EMP 600 mg/m2 on days 1
      to 42 and vinblastine 4 mg/m2 intravenously (IV) once a week for 6 weeks. Courses
      were repeated every 8 weeks. Response assessment was based on a change in serum
      prostate-specific antigen (PSA) levels and was correlated with change in pain
      scores. RESULTS: PSA decreased from baseline by at least 50% in 22 patients
      (61.1%) and by > or = 75% in eight patients (22.2%). A 50% or more decrease in
      PSA on three successive 2-week measurements together with an improved or stable
      pain score, performance status, and measurable soft tissue disease (if present)
      was required for a partial response (PR), which occurred in 11 patients for an
      overall response rate of 30.5% (95% confidence interval, 15.6% to 45.6%). In
      seven patients with measurable nonosseous disease, there was one PR (14%) and one
      minor response (MR). In 28 patients with assessable pain, major pain responses
      occurred in 12 (42.9%). PSA response (> or = 50% decrease times three
      measurements) was predictive of major pain response with a 93.7% specificity, a
      50% sensitivity, and a positive predictive value of 85.7%. CONCLUSION: We
      conclude that EMP and vinblastine is an active combination in hormone-refractory
      prostate cancer.

PMID- 1383437
TI  - The impact of chemotherapy on the quality of life of breast cancer patients.
AB  - One hundred and thirty-seven breast cancer patients, 102 receiving adjuvant
      chemotherapy and 35 receiving palliative chemotherapy for metastatic disease
      underwent a 37-item quality-of-life questionnaire to evaluate the impact of
      disease and treatment on physical, psychological and social well being. Patient
      groups were designated as follows--Adj CT: patients undergoing the questionnaire
      during their adjuvant chemotherapy program; Post Adj CT: patients evaluated 3 to
      8 months after termination of adjuvant chemotherapy; Mts CT: patients assessed
      during palliative chemotherapy for metastatic disease, and Post Mts CT: patients
      3 to 8 months after termination of palliative chemotherapy. Physical and social
      activities were reported as unaltered or normal by 64 to 70% and 52 to 67% of
      patients, respectively. Psychological status was judged normal by 39 to 45% of
      patients. No significant differences were observed between the patients groups.
      In 83 to 90% of cases the patient normally took care of herself. In 62 to 87% of
      cases time dedicated to recreational activities was reported as unaltered. The
      majority of patients (84%) judged that their relationship with partner and/or
      family were good. Severe anxiety was reported in 19 to 28% of patients and severe
      depression was infrequent (3.9%). Information regarding disease and treatment
      given by health professionals was considered satisfactory by 80 to 100% of
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383438
TI  - Principles of removable partial denture design.

PMID- 1383439
TI  - Procedures: a selection of clinical and laboratory.

PMID- 1383440
TI  - Metal frameworks for removable partial overdentures.

PMID- 1383441
TI  - A combined semiprecision/conventional removable partial denture.

PMID- 1383442
TI  - The bilateral distal extension base removable partial denture.

PMID- 1383443
TI  - Removable partial denture design assisted by osseointegrated implants.

PMID- 1383445
TI  - Overview of some credential requirements.

PMID- 1383444
TI  - States divided.

PMID- 1383446
TI  - Identifying fire victims: the East Bay firestorm.

PMID- 1383447
TI  - Who says no?

PMID- 1383448
TI  - U.S. health care system: terminally ill?

PMID- 1383449
TI  - Communication roundtable.

PMID- 1383450
TI  - Neurolinguistic programming in dentistry.

PMID- 1383451
TI  - Neutralizing dental fear.

PMID- 1383452
TI  - Communicating to avoid liability.

PMID- 1383453
TI  - Getting a yes....

PMID- 1383454
TI  - The art of effective referrals.

PMID- 1383455
TI  - Carpal tunnel syndrome.

PMID- 1383456
TI  - Calcium sulfate: an aid to periodontal, implant and restorative therapy.

PMID- 1383457
TI  - Button, button, who gets the button?

PMID- 1383459
TI  - Restorative options with dental implants.

PMID- 1383458
TI  - Considerations for implant overdentures.

PMID- 1383460
TI  - Surgical planning.

PMID- 1383461
TI  - Addressing the options.

PMID- 1383462
TI  - Is it a tooth or an implant?

PMID- 1383463
TI  - Dental implants in the predoctoral curriculum.

PMID- 1383464
TI  - ADA acceptance program for endosseous implants.

PMID- 1383465
TI  - Implant economics.

PMID- 1383466
TI  - HA-coated dental implants: long-term consequences.

PMID- 1383467
TI  - Treatment of the ailing, failing implant.

PMID- 1383468
TI  - Balancing act.

PMID- 1383469
TI  - The high lip line: a practical approach.

PMID- 1383470
TI  - The enamel ceramic alternative: porcelain veneers vs metal ceramic crowns.

PMID- 1383471
TI  - Bloodborne exposure incidents: complying with OSHA regulations.

PMID- 1383472
TI  - The health-centered practice: a new model for the '90s.

PMID- 1383473
TI  - Connective tissue membrane: treating grade II furcation involvements.

PMID- 1383474
TI  - The great handpiece fiasco.

PMID- 1383475
TI  - Depolarization increases vasoactive intestinal peptide- and substance P-like
      immunoreactivities in cultured neonatal and adult sympathetic neurons.
AB  - Depolarization has been shown to alter the biosynthesis of a number of
      neurotransmitters and neuromodulators. In the rat superior cervical ganglion
      (SCG), for example, depolarization has been reported to increase catecholamine
      biosynthesis and to decrease the level of substance P. We have recently found
      that, although the level of vasoactive intestinal peptide (VIP)-like
      immunoreactivity (IR) is normally low in the SCG, it increases significantly 48
      hr after adult ganglia are deafferented in situ or placed in organ culture. Both
      manipulations decrease electrical activity of postganglionic neurons. To
      determine whether the increases in ganglionic VIP-IR could be a consequence of
      decreased depolarization of sympathetic neurons, the effect of depolarization on
      the expression of VIP-IR was examined in organ cultures of neonatal and adult
      SCG. Depolarization with elevated K+ (30 mM) or veratridine (1.5 microM)
      amplified, rather than blocked, the increases in VIP-IR content seen after 24 hr.
      Further, it increased the number of detectable VIP-IR neuronal cell bodies and
      processes. The stimulatory effects of veratridine were prevented by TTX. Since
      similar changes in expression of VIP-IR were evident in dissociated cell cultures
      of the SCG, cell-cell interactions requiring intact ganglionic architecture are
      not necessary for altered peptide expression. Elevating the concentration of Mg2+
      blocked the ability of K+ and veratridine to increase VIP-IR in dissociated cell
      culture, raising the possibility that the effects of depolarization on VIP-IR are
      mediated by increased Ca2+ entry. The depolarizing conditions that increased VIP
      IR also increased substance P-IR. While higher concentrations of veratridine (50
      microM) blocked the elevation of both VIP- and substance P-IR induced by
      explantation, they produced significant neuronal death. Since depolarization with
      either 30 mM KCl or 1.5 microM veratridine increases expression of VIP-IR in
      neonatal and adult ganglia, decreased depolarization is unlikely to cause the
      increases in VIP- and substance P-IR that occur in culture. Furthermore, our data
      raise the possibility that sympathetic nerve activity in vivo can increase
      expression of these peptides.

PMID- 1383476
TI  - Protein kinase A reduces voltage-dependent Na+ current in Xenopus oocytes.
AB  - The voltage-dependent Na+ channel of the brain is a good substrate for
      phosphorylation by the cAMP-dependent protein kinase (protein kinase A, or PKA),
      but the physiological effects of PKA on Na+ channels are poorly documented. We
      studied modulation by PKA of voltage-dependent Na+ channels expressed in Xenopus
      oocytes injected with RNA coding for the alpha-subunit of the channel protein
      (rat brain type IIA and its variant VA200), using the two electrode voltage-clamp
      technique. Intracellularly injected cAMP or catalytic subunit of PKA, or
      extracellularly applied forskolin, inhibited the Na+ current by 20-30%. The
      effect of cAMP was attenuated by prior injection of PKA inhibitors. Injection of
      small doses of protein phosphatase 2A increased the Na+ current by 10%, whereas
      larger doses of protein phosphatase 1 and alkaline phosphatase were without
      effect. The inhibition by PKA showed little voltage dependence, being only
      slightly stronger at holding potentials at which the availability of the channels
      was reduced. The voltage dependence of activation and inactivation processes was
      not altered by cAMP. Similar effects were exerted by forskolin and cAMP on the
      Na+ channels expressed after the injection of heterologous (total) RNA from rat
      brain. Thus, PKA modulates the Na+ channel by a mechanism that does not involve
      major changes in the voltage dependency of the current and is exerted on the
      channel-forming alpha-subunit.

PMID- 1383477
TI  - Cyclic nucleotides mediate an odor-evoked potassium conductance in lobster
      olfactory receptor cells.
AB  - Odors activate at least two distinct transduction pathways in lobster olfactory
      receptor cells that, respectively, excite and inhibit the cell. Data presented
      suggest that odors selectively activate the inhibitory conductance through the
      second messenger cAMP. Not all cells support both odor-evoked excitatory and
      inhibitory conductances; in the current investigation, about 50% of the cells
      tested were inhibited by odors. In the majority of cells that, as a group,
      support an inhibitory response to odor stimulation, activation of adenylate
      cyclase with forskolin or inhibition of phosphodiesterase activity with 3
      isobutyl-1-methylxanthine (IBMX) elicits an outward current with a time course
      similar to that of odor-evoked outward currents. The membrane-permeant cyclic
      nucleotide analogs 8-Br-cAMP and 8-Br-cGMP have a similar effect. Forskolin and
      IBMX enhance the magnitude of odor-evoked outward currents when the drug and the
      odor are copresented to the cell. In contrast, these same drugs have little or no
      effect on cells that, as a group, fail to support an inhibitory response to odor
      stimulation. This study provides the first direct evidence implicating cAMP in
      olfactory transduction in an invertebrate and contrasts with similar studies in
      vertebrates that have implicated cAMP as a second messenger mediating excitation.

PMID- 1383478
TI  - Regional cerebral perfusion in Landau-Kleffner syndrome and related childhood
      aphasias.
AB  - Assessment of cerebral perfusion may elucidate pathogenesis of Landau-Kleffner
      syndrome (LKS). We obtained 99mTc-HMPAO SPECT studies in five children with LKS
      and in three children with syndromes of verbal-auditory agnosia. In LKS,
      perfusion showed temporoparietal asymmetry (9.56% +/- 3.44%) (n = 4) or bilateral
      parietal abnormality (n = 1). SPECT in non-LKS patients was normal (n = 1),
      showed (n = 1) totihemispheral hypoperfusion accompanying structural abnormality
      or (n = 1) a pattern resembling but distinct from LKS. Seizures in LKS patients
      had never occurred (n = 1), were controlled satisfactorily (n = 2), or poorly (n
      = 2). Maximum EEG abnormality was left centrotemoral-occipital (n = 1), left
      frontocentral (n = 1), bitemporal/left central (n = 1), and left
      central/parasagittal (n = 1). Asymmetric temporoparietal perfusion appears
      characteristic of LKS, differing from findings in other childhood linguistic
      disturbances. This abnormality occurs across a spectrum of seizure expression,
      diverging from the distribution of EEG abnormalities. The SPECT abnormalities
      parallel PET-defined LKS metabolic abnormalities, and may indicate central
      pathogenetic features of the disorder.

PMID- 1383479
TI  - Fetal cleft lip repair in rabbits: histology and role of hyaluronic acid.

PMID- 1383480
TI  - An immunoenzymometric assay for a CA125-like antigen, CA602.
AB  - An immunoenzymometric assay (IEMA) for a new CA125-like antigen, CA602, was
      developed. Five monoclonal antibodies raised against a human ovarian carcinoma
      cell line could detect their respective antigens in the sera of ovarian carcinoma
      patients. The antigen levels detected in serum by the various antibodies
      correlated significantly to each other, and to CA125 levels. The results of
      epitope analyses and combined IEMAs suggested that the epitopes recognized by
      these antibodies are not same, but exist on the same antigen which bears the
      CA125 epitope. A sensitive IEMA was developed with 602-1 and 602-6 antibodies
      which showed high reactivity to the CA125-like antigen. The antigen defined by
      these two antibodies was designated as CA602, and serum CA602 levels correlated
      well with CA125 levels. The CA602 antigen is a CA125-like antigen. Furthermore,
      the serum CA602 levels did not correlate to CA54/61 levels. The combined assays
      of CA602 and CA54/61 may increase the detection of ovarian carcinoma.

PMID- 1383481
TI  - Chromatographic characterization of CA 19-9 molecules from cystic fibrosis and
      pancreatic carcinoma.
AB  - We have compared the size, the binding to Concanavalin A (Con A), and the
      affinity for monoclonal antibody 1116NS-199 (Mab 19-9) among CA 19-9 molecules
      from sera of cystic fibrosis (CF) and pancreatic carcinoma patients and from
      sputum extracts. CA 19-9 molecules of two different sizes were found in all types
      of specimens by Sepharose 4B chromatography. While the smaller CA 19-9 molecule
      was predominant in CF patient sera, the larger molecule was associated with most
      of the sera from patients with pancreatic carcinoma. The majority of the sputum
      extracts contained the larger CA 19-9 molecule. All CA 19-9 molecules studied by
      Con A chromatography did not appear to bind to Con A, and almost 100% were found
      in the nonreactive fraction. The CA 19-9 molecules from sera of either CF or
      pancreatic carcinoma patients exhibited variable affinities for Mab 19-9, some
      approaching that of the standard curve but many also having lower affinities. The
      lowest affinity was displayed by CA 19-9 molecules from the sputum extract. It
      appears that development of more specific assays for CF and for carcinoma is
      possible if the correct CA 19-9 molecule is selected for antibody preparation and
      for use as standards.

PMID- 1383482
TI  - Specificity of a tumor marker (CA54/61) and its individual epitopes recognized by
      monoclonal antibodies, MA54 and MA61, in human tumor patients.
AB  - The specificity of a tumor marker (CA54/61) and its individual epitopes (CA54 and
      CA61) recognized by monoclonal antibodies (MA54 and MA61) and expressed by the
      same tumor marker were studied. Serum levels of CA54 and CA61 were compared with
      that of CA54/61. In lung adenocarcinoma and ovarian carcinoma, the positive rates
      of CA61 (42% and 68%) were higher than those of CA54 (32% and 32%) and similar to
      those of CA54/61 (45% and 74%). The serum levels of CA54 and CA61 showed a
      significant correlation (r = 0.78), but 22% of tested sera were positive for CA54
      and negative for CA61 or negative for CA54 and positive for CA61. It was
      demonstrated that the tumor specificity between CA54 and CA61 was not same and
      that the tumor specificity of CA54/61 was similar to that of CA61 rather than
      CA54. Moreover, the difference in the tumor specificity between CA54 and CA61 was
      considered to be reflected in the difference in their epitope structure.

PMID- 1383484
TI  - Alteration of stromal protein and integrin expression in breast--a marker of
      premalignant change?
AB  - Interactions between epithelia and the extracellular matrix are important in the
      modulation of cellular growth, differentiation, and motility. To investigate the
      possible roles of these interactions in the neoplastic process, this study
      examines the expression of the integrin subunits a2, a6, beta 1, and beta 4 and
      the stromal protein tenascin in 53 breast carcinomas, non-involved breast tissue
      from 21 of these cases, and 32 normal/benign cases. Frozen tissue and an indirect
      immunoperoxidase technique were used throughout. Linear staining in relation to
      the basement membrane was seen for all integrins in the normal/benign cases. The
      carcinomas showed complete loss of reactivity in 65 per cent of cases for a2, 80
      per cent for a6 and beta 4, and 90 per cent for beta 1. Those showing reactivity
      displayed a diffuse cytoplasmic type of staining. The non-involved breast tissue
      showed linear basement membrane type staining with a2 and beta 1, but for a6 and
      beta 4 66 per cent of cases displayed reactivity identical to that of the
      corresponding tumour. For tenascin, band-like staining around ducts was seen in
      normal/benign cases, with a diffuse coarse reactivity in all carcinomas. Most non
      involved cases stained as for normal breast. The altered a6 beta 4 integrin
      staining in non-involved tissue in cancerous breast may be an early event in the
      neoplastic process, and as such, may be of use as a marker of pre-malignant
      change.

PMID- 1383483
TI  - Monoclonal antibodies to beta subunit of choriogonadotropin: development and use
      in a sandwich ELISA pregnancy test.
AB  - Balb/c mice were immunized with beta subunit isolated and purified from crude
      human chorionic gonadotropin preparations. Spleen cells from the higher titered
      mouse were fused with Sp 2/0 myeloma cells. Four specific secreting hybridomas
      were obtained. Specificity, affinity, and suitability of secreted antibodies for
      use in enzyme immunoassays were studied. Ascites of the selected hybridoma was
      raised; the antibody was purified by protein A-affinity chromatography and
      coupled to horseradish peroxidase. This conjugate was employed in a simultaneous
      sandwich enzyme immunoassay on microtiter plates sensitized with goat polyclonal
      antibody to measure the hormone. The test has a sensitivity of 10 mlU/ml either
      on urine, serum, or plasma samples when read in a microplate reader. The results
      can also be evaluated by the naked eye, with a sensitivity of 20 mlU/ml. No cross
      reactivity was detected with other human gonadotropins.

PMID- 1383485
TI  - Cytokeratin immunohistochemical examination of liver biopsies in infants with
      Alagille syndrome and biliary atresia.
AB  - Identifying bile duct epithelium is sometimes difficult with standard histologic
      techniques. The availability of antibodies to specific cytokeratin (CK)
      intermediate filaments has allowed identification of CK expressed by bile duct
      epithelium. Formalin-fixed, paraffin-embedded liver tissue from five infants
      (aged 1-12 months) with Alagille syndrome and five infants with biliary atresia
      (aged 1.5-11 months) were pepsin digested then reacted with a combination of anti
      cytokeratin monoclonal antibodies using an avidin-biotin immunoperoxidase
      technique. Liver tissue obtained at autopsy from infants without primary liver
      disease (aged 22 weeks gestation to 24 months) was treated similarly for
      comparison. Control specimens showed progression from prominent immunoreactivity
      of the ductal plate cells at the rim of the portal tract (22-24 weeks gestation)
      to incorporation of tubular ductal structures into portal tract mesenchymal
      tissue (26-34 weeks gestation) and formation of intensely immunoreactive mature
      discrete interlobular ducts with progressive loss of cytokeratin immunoreactivity
      of the ductal plate cells (1-24 months). In contrast, biopsies from infants with
      Alagille syndrome showed few immunoreactive interlobular ducts. Biopsies from
      infants with Alagille syndrome less than 2 months old showed only
      immunoreactivity of single ductal plate cells or small ductules at the periphery
      of the portal tracts. Biopsies from some infants greater than 3 months old showed
      increased numbers of immunoreactive cells in groups and anastomosing bands
      lacking true lumens and extending into the fibrous bridges between adjacent
      portal areas (neoductular proliferation).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383486
TI  - The treatment of simultaneous choriocarcinoma in mother and baby.
AB  - Simultaneous occurrence of choriocarcinoma in mother and child is rare. Such a
      case is described in which a massive intrahepatic tumor in the infant led to its
      treatment and that of the mother who showed evidence of the same tumor. Both are
      alive and well 1 year after treatment, the longest recorded infant survival.

PMID- 1383487
TI  - Detection of, and anti-collagen antibody produced by, CD5-positive B cells in
      inflamed gingival tissues.
AB  - This study was performed to investigate the frequency and distribution of CD5
      positive (CD5+) B cells in inflamed gingival tissues using flow cytometric and
      immunohistochemical analyses. The ability of CD5+ B cells to produce anti-type I
      collagen antibody was also examined. CD5+ B cells expressed "low" fluorescence
      intensity in the peripheral blood of both healthy subjects and patients with
      adult periodontitis. However, in inflamed gingival tissues the intensity of this
      surface marker was high. The percentage of B cells bearing CD5 surface marker was
      statistically higher in gingiva than in peripheral blood obtained from both the
      patients and healthy subjects. These CD5+ B cells were observed in gingival
      subepithelial connective tissues from the bottom to the middle of the periodontal
      pocket. This area showed destruction of collagen fibers and dense cell
      infiltrations. Anti-collagen IgG antibody level in patients' gingival crevicular
      fluids (GCF) was higher than that in sera from healthy subjects, and slightly
      higher than in autologous sera. IgM anti-collagen antibody in GCF was lower than
      in autologous sera and in sera from healthy subjects. EBV-transformed CD5+ B
      cells produced considerably more IgM and IgG antibody to collagen than CD5- B
      cells. Therefore CD5+ B cells may contribute to the pathogenesis of inflamed
      gingival tissues.

PMID- 1383488
TI  - [Current acquisitions in antiviral drugs (anti-HIV)].
AB  - These last years, numerous molecules have been developed to face HIV-1 infection.
      All viral replication steps are potential targets for new molecules. The most
      potent inhibitors of virus-cell adsorption are represented by the different
      sulfated, sulfonated and carboxylated polymers among which aurintricarboxylic
      acid (ATA). The soluble CD4 are also potent inhibitors of viral adsorption in
      vitro. Many compounds are active at the level of the reverse transcriptase (RT),
      particularly the 2',3'-dideoxynucleosides, represented by the three currently
      most used drugs in the clinic, AZT, ddC and ddI. The acyclic nucleoside
      phosphonates (PMEA, PMEDAP) have shown a broad spectrum activity against many
      human and animal retroviruses, and also unique pharmacological properties
      allowing infrequent administration. Finally, most recently, highly potent
      activity, without toxicity, has been demonstrated by TIBO, HEPT and other HIV-1
      RT-specific inhibitors.

PMID- 1383489
TI  - Synergistic action of melatonin and vasoactive intestinal peptide in stimulating
      cyclic AMP production in human lymphocytes.
AB  - In the present study we investigated the synergistic effect of melatonin and
      vasoactive intestinal peptide (VIP) on cyclic AMP production in human blood
      lymphocytes. As shown by our group previously, VIP alone behaved as a potent
      activator of cyclic AMP production in human lymphocytes. On the other hand,
      melatonin alone did not affect the intracellular levels of cyclic nucleotide at
      any time or dose studied. However, when cells were incubated with melatonin plus
      VIP, melatonin potentiated the effect of the peptide. This effect can be observed
      in the presence of physiological doses of both melatonin (10-100 pM) and VIP (1
      100 pM). The effect is specific for VIP because with other peptides belonging to
      the secretin-VIP family the effect was not observed. Results suggest that
      melatonin, in conjunction with VIP, may directly participate in the regulation of
      immune function in the human.

PMID- 1383490
TI  - Di-iodo-L-tyrosine-labelled dextrans as molecular size markers of nasal
      absorption in the rat.
AB  - A series of fractionated di-iodo-L-tyrosine-labelled dextrans (DIT dextrans),
      with a narrow range of number average molecular weights from 1260 to 45,500 Da,
      was administered intranasally and intravenously to anaesthetized rats. The nasal
      absorption of these compounds ranged from 0.6 to 52.7%. There was an inverse
      relationship between molecular size and the proportion of an intranasal dose
      absorbed. The study demonstrated the usefulness of DIT dextrans as molecular
      weight markers and confirmed the relationship between molecular size and nasal
      absorption for highly water soluble compounds. These results also supported the
      proposition that there is a continuous range of aqueous pores in the nasal
      mucosa.

PMID- 1383491
TI  - Transient stimulation of granulopoiesis and drastic inhibition of erythropoiesis
      in HIV-2-infected long-term liquid bone marrow cultures.
AB  - Impaired hematopoiesis is commonly associated with human immunodeficiency virus
      HIV-1 and HIV-2-related AIDS. HIV-1 infection of hematopoietic progenitors has
      been studied, whereas HIV-2 infection of these cells is less well documented. In
      this work, we studied myeloid and erythroid progenitor production and
      differentiation in long-term bone marrow (LTBM) cultures after HIV-2 infection. A
      nonadherent fraction from these cultures containing the hematopoietic progenitors
      is nonproductively infected with HIV-2, whereas stroma cells replicate the virus
      only weakly. HIV-2 can be rescued from nonadherent T-depleted bone marrow cells,
      and its replication in stroma cells is amplified by cocultivation with HIV
      permissive cells. Colony assays performed weekly during the 6 weeks of LTBM
      cultures revealed a 100% inhibition of erythroid colony-forming unit (CFU)-E and
      erythroid burst-forming unit (BFU)-E production after 12 days of culture, whereas
      granulomonocytic colony forming units (CFU-GM) production was stimulated until
      day 20 and then disappeared on day 30. Stimulatory and inhibitory activities were
      recovered from supernatants of infected LTBM cultures and an infected lymphoid
      CEM cell line, suggesting that release of viral factor(s) may be responsible for
      HIV-2-induced impairment of hematopoietic progenitor production in vitro. Based
      on these results, an indirect effect of HIV-2 infection on the commitment of
      myeloid and erythroid progenitors, resulting in a dysregulated hematopoiesis, is
      postulated.

PMID- 1383492
TI  - Ciwujianosides D1 and C1: powerful inhibitors of histamine release induced by
      anti-immunoglobulin E from rat peritoneal mast cells.
AB  - In rat peritoneal mast cells induced by anti-immunoglobulin E, ciwujianosides D1
      (1) and C1 (2) from Acanthopanax senticosus (ciwujia) strongly inhibited
      histamine release in a concentration-dependent manner. The inhibitory effect of 1
      was approximately 6800 times stronger than that of disodium cromoglycate.

PMID- 1383493
TI  - Chronic administration of the antidepressant-antipanic drug phenelzine and its N
      acetylated analogue: effects on monoamine oxidase, biogenic amines, and alpha 2
      adrenoreceptor function.
AB  - Phenelzine (PLZ), a nonselective monoamine oxidase inhibitor, is widely used in
      psychiatry for the treatment of panic disorder and depression. The effects of
      chronic (28-day) administration of PLZ (0.05 mmol/kg/day) and its N-acetylated
      analogue, 1-acetyl-2-(2-phenylethyl) hydrazine (N2-acetylphenelzine; N2AcPLZ;
      0.10 mmol/kg/day), on alpha 2-adrenoreceptor function were investigated by use of
      a behavioral test on days 21 and 22. Rats treated with PLZ or N2AcPLZ displayed a
      significant attenuation of the suppressant effects of clonidine on spontaneous
      locomotor activity, compared with controls; these results suggest a reduced
      sensitivity of alpha 2-adrenoreceptors. By day 28, both PLZ and N2AcPLZ had
      produced greater than 85% inhibition of monoamine oxidases A and B in the brain,
      heart, and liver. Both drugs induced significant elevations of whole-brain levels
      of noradrenaline, 5-hydroxytryptamine, and dopamine, compared with those in
      controls. The levels of acid metabolites of dopamine and 5-hydroxytryptamine
      (homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole-3-acetic
      acid) were significantly reduced in both groups of drug-treated animals.

PMID- 1383495
TI  - S-[2-(4-imidazolyl)ethyl]isothiourea, a highly specific and potent histamine H3
      receptor agonist.
AB  - The effects of a new agonist of histamine (HA) H3 receptors, Imetit (S-[2-(4
      (imidazolyl)ethyl]isothiourea) were investigated in vitro and in vivo and
      compared to those of (R)-alpha-methylhistamine [(R)-alpha-MeHA], a prototypic
      drug. Imetit inhibited the binding of [3H](R-alpha-MeHA to rat brain membranes
      with a Ki value of 0.1 +/- 0.01 nM. The release of endogenously synthesized
      [3H]HA induced by K(+)-depolarization from rat brain slices and synaptosomes was
      inhibited by Imetit with EC50 values of 1.0 +/- 0.3 and 2.8 +/- 0.7 nM,
      respectively. Imetit behaved as a full agonist and was about 4 times more potent
      than (R)-alpha-MeHA and 60 times more potent than HA. Thioperamide, a selective
      H3 receptor antagonist, elicited a parallel rightward shift of the concentration
      response curve for Imetit with an apparent Ki value of 5.6 +/- 1.4 nM. Imetit
      potencies relative to HA were less than 0.1% and only 0.6% at HA H1 and H2
      receptor reference systems, respectively. Imetit was found not to be a substrate
      or an inhibitor of HMT. After p.o. administration to mice or rats, Imetit
      decreased (by approximately 50%) the tele-MeHA level in the cerebral cortex with
      ED50 values of 1.0 +/- 0.3 and 1.6 +/- 0.3 mg/kg, respectively. This effect was
      still maximal after 6 hr. The in vivo potency and duration of action of Imetit
      were in the same range as those of (R)-alpha-MeHA. It is therefore concluded that
      Imetit represents a new potent and selective HA H3 receptor agonist.

PMID- 1383494
TI  - Characterization of [125I]acidic fibroblast growth factor binding to the cloned
      human fibroblast growth factor receptor, FGF-flg, on NIH 3T3 cell membranes:
      inhibitory effects of heparin, pertussis toxin and guanine nucleotides.
AB  - The present studies were conducted to characterize the specific binding of
      recombinant human [125I]acidic fibroblast growth factor ([125]aFGF) to the cloned
      human fibroblast growth factor (FGF) receptor, flg, overexpressed on stably
      transfected NIH 3T3 mouse fibroblast (NFlg26) cell membranes. In the presence of
      5 U/ml of heparin to block [125I]aFGF binding to membrane bound heparan sulfate
      proteoglycans, specific [125I]aFGF binding was optimal in the presence of 0.2 M
      NaCl and in a pH range of 7 to 9. [125I]aFGF labeled a single class of
      recognition sites with high affinity (Kd = 0.27 nM) and limited capacity
      (apparent maximum binding = 19.5 pmol/mg of protein). A similar estimate of
      ligand affinity (Kd = 0.25 nM) was determined from association and dissociation
      rate experiments. aFGF, basic fibroblast growth factor and several glycine
      substituted point mutations of aFGF potently inhibited 0.1 nM [125I]aFGF binding.
      A variety of putative FGF receptor ligands including poly-L-lysines and poly-L
      arginines, protamine, suramin and wheat germ agglutinin were shown to have weak
      or no affinity for the [125I]aFGF recognition site. Additional saturation
      studies, conducted in the presence of a lower (0.1 U/ml) heparin concentration,
      indicated that [125I] aFGF labeled both the high affinity (Kd = 0.02 nM) FGF-flg
      receptor and a separate class of lower affinity (Kd = 2 nM) recognition sites.
      Pretreatment of NFlg26 cell membranes with pertussis toxin resulted in a heparin
      dependent decrease in the binding affinity (Kd values of 0.57-1.15 nM) of
      [125I]aFGF. Similar pretreatment with cholera toxin did not significantly affect
      [125I] aFGF binding. Guanine nucleotides were also found to significantly reduce
      0.1 nM [125I]aFGF binding in a heparin-dependent fashion. The present data
      demonstrate that, in the presence of heparin, [125I]aFGF binds with high affinity
      to the cloned FGF-flg receptor on NFlg26 cell membranes. However, at a low
      heparin concentration (0.1 U/ml), [125I]aFGF binds to the FGF-flg receptor with
      higher affinity than was observed in the presence of 5 U/ml of heparin, and also
      binds a class of lower affinity recognition sites which are consistent with the
      labeling of cell surface heparan sulfate proteoglycans. The present data also
      indicate that agents which are known to interfere with receptor/G-protein
      coupling reduce the binding affinity of [125I]aFGF and suggest that the FGF-flg
      receptor may be coupled to a G-protein in addition to its intrinsic tyrosine
      kinase activity.

PMID- 1383496
TI  - Imipramine's selective suppression of an L-type calcium channel in neurons of
      murine dorsal root ganglia involves G proteins.
AB  - The whole cell recording technique was used to explore the depressant effect of
      the tricyclic antidepressant imipramine (IP) on calcium currents of neurons in
      cultures of murine dorsal root ganglia. The maximal whole cell current (ICa)
      mediated by the L-type calcium channel declined to 54% of control within 3 min of
      superfusing neurons with a solution containing 30 microM IP. In contrast, the T
      type calcium current was unchanged. The IP-induced reduction of ICa was not
      associated with a change of the current-voltage relations of ICa. The depressant
      effect of IP on ICa was greatly reduced if neurons were pretreated with pertussis
      toxin or dialyzed with an intracellular solution containing guanosine 5'-O-2
      thiodiphosphate. In contrast, superfusion of neurons with 5 mM 8-bromo-cyclic-AMP
      did not alter the effect of IP upon ICa. These data suggest that the selective
      suppressant effect of IP on the L-type calcium channel involves either an
      interaction with that region of the channel complex coupled to guanosine
      nucleotide-binding proteins or with guanosine nucleotide-binding proteins
      themselves.

PMID- 1383497
TI  - Activation and desensitization of embryonic-like receptor channels in mouse
      muscle by acetylcholine concentration steps.
AB  - 1. Pulses of acetylcholine (ACh) in concentrations between 0.1 and 1000 microM
      were applied repetitively to outside-out patches of enzymatically denervated (14
      days) mouse muscle with the liquid filament switch. Solutions superfusing the
      patch could be changed rapidly (within 0.2 ms). 2. Single-channel activity was
      studied under steady-state conditions in the outside-out and in the cell-attached
      mode. The single-channel conductance was 26 pS in outside-out patches,
      characteristic for embryonic-like channels. Apparent mean open time was about 2.5
      ms, a shorter component of closed times was 800 microseconds and burst length was
      about 5 ms. 3. Channel currents elicited by pulses of ACh were averaged. The time
      to-peak current was concentration dependent and decreased from a level of about
      10 ms below 10 microM to about 400 microseconds at 100 microM-ACh. 4. For a
      typical experiment, the average peak current, imax, increased from -0.4 pA with
      0.1 microM to -82 pA with 1000 microM-ACh, close to the value at saturation. The
      half-maximal response was at 60 microM-ACh. The dose-response curves for imax had
      double-logarithmic slopes of 1.1-1.3, consistent with two binding sites at the
      embryonic nicotinic acetylcholine receptor (nAChR). 5. The current elicited by
      ACh pulses decreased rapidly after the peak. The time constant of desensitization
      increased from 20-50 ms with 1000 microM-ACh to up to more than a second with 1
      microM-ACh. 6. The current in steady state (fully desensitized) increased up to
      10 microM-ACh, but decreased slightly to values of imax/100 to imax/500 when
      higher concentrations were applied. 7. In addition to the well-known differences
      between adult and embryonic nAChR concerning the apparent mean open time and
      burst length, we found differences in the slope of the dose-response curve for
      imax, in the ratio of peak to steady-state response, and in the rise time of the
      response.

PMID- 1383498
TI  - Characterization of membrane currents in single smooth muscle cells from the
      guinea-pig gastric antrum.
AB  - 1. Smooth muscle cells, enzymatically isolated from the antrum of the guinea-pig
      stomach, were voltage clamped at room temperature using the whole-cell patch
      clamp technique. In physiological salt solution (PSS), step depolarization from a
      holding potential of -90 mV elicited inward calcium current (ICa) followed and
      superimposed by outward potassium current. 2. Outward current was divided into
      components depending on the presence of extracellular Ca2+ and others which were
      not activated as a result of Ca2+ influx. Ca(2+)-dependent components were (1) a
      fast transient component most likely representing Ca(2+)-activated K+ current
      (IK(Ca)) immediately triggered by the initial peak of ICa and (2) spontaneous
      transient outward currents (STOCs) apparently reflecting synchronized opening of
      IK(Ca) channels by cyclic release of Ca2+ from intracellular stores. Ca2+ influx
      independent outward current could be divided into two main components: (1) a
      transient component (I(to)) showing voltage-dependent activation and inactivation
      and (2) a non-inactivating component (Ini). 3. I(to) activated with a threshold
      around -30 mV, was fully available at -90 mV and completely inactivated at -10
      mV. The time course of both activation and inactivation of I(to) at different
      potentials could be described by single exponential functions. Time constants of
      activation decreased from 35 ms at -10 mV to 10 ms at +40 mV. The time constant
      of inactivation was about 2 s and only weakly voltage dependent. Time constants
      for exponentially developing recovery from inactivation of I(to) ranged from 0.1
      s at -100 mV to 10 s at -30 mV. I(to) was insensitive to 4-aminopyridine (4-AP, 5
      mmol/l), slightly sensitive to tetraethylammonium (TEA, 10 mmol/l), but
      substantially inhibited by caffeine (10 mmol/l) and Cd2+ (5 mmol/l). Estimates of
      the single-channel conductance by current fluctuation analysis indicated a small
      value of about 2.5 pS. 4. The action of TEA on current elicited from a holding
      potential of -10 mV indicated a major contribution to Ini of a distinct component
      (Ini,K) that was completely blocked by this substance at a concentration of 10
      mmol/l. Ini was almost unaffected by 4-AP (5 mmol/l) and caffeine (10 mmol/l),
      but strongly suppressed by Cd2+ (5 mmol/l). Current fluctuation analysis of Ini,K
      gave a value for the single-channel conductance of about 60 pS. 5. Ca2+ inward
      current was studied in PSS ([Ca2+]o = 2.5 mmol/l) using pipette solution in which
      K+ was replaced by Cs+ to suppress outward K+ currents.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1383499
TI  - Distribution of adhesion receptors in recurrent oral ulcers.
AB  - When activated under physiologic or pathologic conditions leukocytes adhere to
      one another or to other cell types. Adhesion receptors mediate these
      interactions. In the study reported here, the distribution of the adhesion
      receptors LFA-1 (CD11a/CD18), ICAM-1 (CD54), CD2 and LFA-3 (CD58) in recurrent
      oral ulcers (ROU) were studied. Nine tissue specimens from five female patients
      (mean age 33 yr, age range 21-40 yr) with ROU were studied using the avidin
      biotin-peroxidase complex (ABC) method. The main mononuclear cell infiltrations
      were in lamina propria (LP) and the epithelium next to the basement membrane
      (BM), laterally to the ulcers. In this area, ICAM-1 was strongly expressed in
      capillaries and in postcapillary venules. LFA-1, LFA-3 and CD2 were expressed in
      65 +/- 1.1%, 70 +/- 16% and 80 +/- 1%, respectively, of all mononuclear cells.
      The findings indicate that LFA-1/ICAM-1 and CD2/LFA-3 interactions may play roles
      in cell to cell adhesion events in ROU.

PMID- 1383500
TI  - Immunoreaction of keratin, actin, S-100 protein and rat-EGF in duct-ligated rat
      salivary glands.
AB  - Duct-ligated submandibular and sublingual glands of rats were evaluated
      immunohistochemically for changes in keratin (MoAb 1164), actin, S-100 protein
      and rat-EGF (rEGF). Normal salivary glands were reactive for keratin, S-100
      protein and rEGF in the granular convoluted tubule (GCT) and duct cells, and for
      actin in the myoepithelium. Submandibular glands showed a marked reduction of S
      100 protein and rEGF staining following duct ligation, and no increased staining
      of proliferating epithelial cells of the late stage in duct ligated glands.
      Sublingual glands revealed no marked changes for actin staining in myoepithelial
      cells, irrespective of atrophic changes occurring in acinar and duct cells after
      duct ligation. Immunohistochemical patterns differed for each type of gland;
      changes associated with the obstructive lesion were more prominent in the
      submandibular gland.

PMID- 1383502
TI  - Cytokeratin profiles in dyskeratosis congenita: an immunocytochemical
      investigation of lingual hyperkeratosis.
AB  - In dyskeratosis congenita, the hyperkeratotic lesions affecting the mucous
      membranes have a propensity to undergo malignant change. Unfortunately there is
      presently no reliable method for predicting such an outcome. Oral mucosal
      biopsies were obtained from a case of dyskeratosis congenita and keratin
      expression identified using a panel of antikeratin antibodies. Marked changes
      were found from keratin profiles established for normal oral mucosa. In
      particular coexpression of three separate type 1 keratins (K16, K10 and K13) were
      observed in the ventral tongue lesion. The keratin pattern found in the tissue
      biopsies examined is suggestive of an unusually immature or disturbed state of
      tissue differentiation, and as such may be indicative of future malignant change.

PMID- 1383501
TI  - Expression of collagenase and potential transcriptional factors c-fos and egr-1
      in periodontal gingival fibroblasts.
AB  - In view of the important role of fibroblast-type collagenase in the pathogenesis
      of periodontal disease (PD), we investigated the expression of this
      metalloproteinase in primary cultures of non-stimulated fibroblasts dissected
      from gingival tissues of patients with generalized moderate and localized severe
      chronic adult PD. Enhanced hybridization signals for collagenase RNA were
      observed in 8/8 PD-cases when compared with equivalent RNA amounts extracted from
      normal fibroblasts. Since both the proto-oncogene c-fos and the "early growth
      response" gene egr-1 might be involved in the transcriptional regulation of the
      collagenase gene expression in vivo, we also compared the relative expression of
      both potential transcriptional factors with collagenase RNA in the same
      fibroblast cytoplasmic extracts. Hybridization signals indicated elevated RNA
      amounts for c-fos in 8/8 PD-cases and for egr-1 in 7/8 PD-cases when compared
      with the cells from non-inflamed tissue. In periodontitis gingival tissue
      specimens, immunolocalization of collagenase could be confirmed in fibroblasts,
      macrophages and epithelial cells in situ. Collagenase label was not widely
      distributed within the tissues, but concentrated at the interface between
      epithelium and connective tissue. The data provide the first evidence that
      gingival fibroblasts producing elevated levels of collagenase RNA amounts express
      also c-fos and egr-1 indicating a crucial role for both genes in cellular
      proliferation and collagenase expression in gingival and periodontal tissue
      destruction in vivo.

PMID- 1383504
TI  - Involucrin expression in some oral lichenoid lesions.
AB  - The aim of this investigation was to assess the reproducibility of a study which
      reported that involucrin could be used as a diagnostic marker in oral lichenoid
      lesions. Twenty-eight formalin-fixed, paraffin-embedded specimens were examined.
      They included tissue from 13 patients with lichen planus, 11 with drug-related
      lichenoid reactions, one with dysplasia in a lichenoid lesion and three with
      normal oral mucosa. In each case the biopsy site was the buccal mucosa, PAS
      stained smears for fungi were negative and immunofluorescence results supported
      the diagnosis. An immunoperoxidase technique was used to demonstrate involucrin
      reactivity. In all sections there was consistent positive staining for involucrin
      in the superficial layers of the epithelium and all the basal layers were
      negative. In conclusion there were no demonstrable differences in the involucrin
      reactivity between the different lesions.

PMID- 1383503
TI  - Direct immunofluorescence of oral mucosal biopsies: a comparison of fresh-frozen
      tissue and formalin-fixed, paraffin-embedded tissue.
AB  - The diagnosis of some oral mucosal diseases can be facilitated by the use of
      direct immunofluorescence. Fresh frozen tissue is preferred when using this
      technique, however frequently the material received by the histopathology
      laboratory has been fixed in formalin. Enzyme digestion of tissue sections glued
      to glass slides prior to incubation with antibodies was shown in this study to
      give comparable results with direct immunofluorescence on fresh frozen tissue and
      can be used for diagnostic purposes when fresh frozen tissue is unavailable or
      not representative of the disease process.

PMID- 1383505
TI  - Immunohistochemical and electronmicroscopic studies of obstructive lesions in
      submandibular glands.
AB  - Obstructive sialoadenitis was examined by immunohistochemical techniques for
      keratin (MoAb KL1, PKK1 and K8.12) and actin. Electronmicroscopy (EMS) was used
      to identify ultrastructural changes in myoepithelial cells and ductal basal
      cells. With immunohistochemistry, actin staining was used as a marker of
      myoepithelium, MoAbs KL1 and PKK1 for ductal luminal cells, and MoAb K8.12 for
      ductal basal cells. Histologic features of the lesion usually showed degenerative
      changes of acinar and duct cells with cell infiltration and fibrous replacement.
      Immunohistochemical findings indicated that actin staining in the changed
      myoepithelial cells was irregularly positive or negative, and also keratin
      staining in luminal and ductal basal cells was reduced or disappeared. Ultra
      structural features of the changed myoepithelial cells indicated that these cells
      appeared less altered than adjacent acinar and ductal cells and showed increased
      amounts of lipid droplets and lipofuscin granules, and also wrinkled processes
      filled the prominent myofilament material.

PMID- 1383506
TI  - Three-dimensional representations of lingual cortical defects (Stafne's) using
      silicone impressions.
AB  - Lingual cortical defects of the mandible are common radiographic entities found
      predominantly in adult males. Due to the benign nature of these defects and
      infrequent need for exploratory surgery, few paleopathologists and clinicians
      have had the opportunity to examine their contents. The present study, using
      silicone impressions, provides three-dimensional representations reflecting the
      size and shape of soft-tissue masses once filling 10 unusually large lingual
      defects. The 10 specimens were chosen from an international sample of 6,330 dry
      mandibles, 115 of which had lingual cortical defects.

PMID- 1383508
TI  - A teaching aid for the visualization of the posterior palatal seal using a
      modified base tray.

PMID- 1383507
TI  - Positively cooperative cAMP phosphodiesterase attenuates cellular cAMP responses.
AB  - We have shown that growth of S49 WT mouse lymphoma cells for 24 hr in 3 nM
      epinephrine produced very significant desensitization of subsequent cellular cAMP
      responses to challenges with higher concentrations of epinephrine. The effects of
      this long-term treatment (LTT) were obvious in intact cells and also when
      adenylate cyclase activity was measured in semi-purified membranes. Beta 2
      adrenergic receptors (beta 2AR) were decreased by LTT, and the desensitization of
      adenylate cyclase was due at least in part to this down-regulation. When mouse L
      cells transfected with WT beta 2AR from hamster lung (L-WT beta 2AR cells) were
      subjected to LTT, the attenuation of adenylate cyclase in membranes was obvious,
      but the consequences of LTT on intact L-WT beta 2AR cells were highly equivocal.
      That is, when the effects of epinephrine on cellular cAMP levels were measured in
      LTT or control L-WT beta 2AR cells little desensitization was apparent. Further,
      cellular cAMP excursions in response to even very high concentrations of
      epinephrine were very small in control L-WT beta 2AR cells as compared to control
      S49 WT cells. Subsequent experiments have shown that L-WT beta 2AR cells possess
      a phosphodiesterase (PDE) which demonstrates marked positive cooperativity with
      cAMP with a Hill coefficient of 2. The EC50 for cAMP hydrolysis was approximately
      30 nM in cell free preparations. cGMP was a positive allosteric effector of the L
      WT beta 2AR cell PDE. Further, when cellular cAMP levels in intact L-WT beta 2AR
      cells were raised above a threshold by treatment with 0.5 microM forskolin and 2
      mM IBMX with the epinephrine challenge, the effect of LLT became obvious in the
      intact cell system. These data demonstrate that cAMP responses to hormones are
      greatly decreased in systems where the predominant PDE demonstrates positive
      cooperativity for cAMP.

PMID- 1383509
TI  - Guidelines for a scientific presentation.
AB  - Guidelines for a projected scientific presentation can assist the speaker in
      preparing an effective audiovisual presentation. This article highlights the
      factors that improve the quality of an audiovisually assisted presentation and
      enhance successful communication.

PMID- 1383511
TI  - The dust has settled--let's sweep it clean: training in minimal access surgery.

PMID- 1383512
TI  - Sutured laparoscopic cholecystojejunostomy evolved in an animal model.
AB  - In a series of acute and chronic experiments conducted in young pigs during a 2
      year period, we have evolved a quick knotting technique to start and end a suture
      line and developed a curved 'Endoski' needle to improve needle passage through
      the tissues. These have been employed in the construction of cholecystojejunal
      anastomoses using a semi-closed technique with a single layer (deep seromuscular)
      of continuous polyglactin sutures. In chronic experiments in pigs, patent well
      healed bilioenteric anastomoses, which conveyed bile satisfactorily after
      ligation of the common bile duct, distal to the cystic duct, were achieved. A
      virtual absence of adhesions in these animals was noted.

PMID- 1383510
TI  - Purification and partial characterization of immobilization antigens from
      Ichthyophthirius multifiliis.
AB  - Ichthyophthirius multifiliis, a parasitic ciliate of freshwater fishes, was found
      to have surface antigens (Ag) which elicited immobilizing antibodies (Ab) when
      injected into rabbits. An effort was made to purify and characterize these Ag
      (referred to as immobilization Ag) because of their potential role in protective
      immunity in fishes. Mice immunized with theront cilia were used for production of
      immobilizing monoclonal antibodies (MAb). Hybridomas were screened by indirect
      immunofluorescent light microscopy and immobilization of live parasites. Six
      hybridomas producing immobilizing MAb were cloned. Immobilizing MAb were used to
      affinity purify Ag solubilized with Triton X-114 and Na deoxycholate. Two
      membrane protein Ag of approximately 48 and 60 kDa were identified. Immobilizing
      MAb failed to react with these Ag on Western blots and, conversely, MAb that
      reacted with the Ag on Western blots did not immobilize live organisms. These
      results suggest that immobilization required native conformational epitopes which
      were altered by Western blotting procedures. Individual MAb reactive on Western
      blots recognized both the 48- and 60-kDa proteins indicating the presence of
      common epitopes. Affinity purified Ag elicited immobilizing antisera when
      injected into rabbits, mice, and channel catfish.

PMID- 1383513
TI  - Paediatric trauma in northern Iraq: the Kurdish refugee crisis.
AB  - In May 1991 a team of five doctors and two nurses from Edinburgh hospitals were
      flown to Northern Iraq to assist in the Kurdish refugee relief effort. The two
      surgical members of the team helped to re-establish surgical services in a small
      hospital in the Iraqi town of Zakho. During an 8-day stay in the hospital,
      frequently in extremely difficult circumstances, the surgical team undertook 19
      major and 15 minor surgical procedures in 25 patients; 11 major and eight minor
      procedures were undertaken in 15 children under the age of 16 years. The largest
      group of children treated had suffered bomb-blast injuries from unexploded
      ordinance; injuries sustained were primarily to the hands, face and upper trunk.
      Road traffic accidents and burns were also common. Two children requiring
      postoperative intensive care were evacuated by military helicopter at night to
      hospital facilities in Turkey.

PMID- 1383514
TI  - Transhiatal oesophagectomy in the management of advanced oesophageal carcinoma.
AB  - Thirty-seven patients have undergone transhiatal oesophagectomy for tumours in
      the upper (n = 3), middle (n = 12) and lower (n = 22) thirds of the oesophagus.
      Four tumours arose in association with Barrett's oesophagus. Dysphagia for solids
      was the presenting symptom in 95% of cases. Orringer's technique was used and all
      cervical anastomoses were hand-sewn. The median duration of surgery was 2.9
      (range 1.5-4.0) h and the 30-day hospital mortality rate was 16% (six patients).
      Respiratory complications were considerable (48%) and accounted for three deaths.
      Median postoperative stay was 21 (range 13-53 days) while median stay in the
      intensive care unit was 8.5 days. The majority (97%) of patients had stage III
      disease and 14 (38%) had lymph node involvement. The actuarial survival was 56%
      at 1 year and 31% at 2 years. Of the operative survivors, 90% resumed normal
      swallowing although 17 (55%) required outpatient dilatation. Transhiatal
      oesophagectomy provides safe and efficient palliation while mortality and 1-year
      survival rates compare with the transthoracic approach.

PMID- 1383515
TI  - Hepatic hydatid cysts: presentation and surgical management in Yemen.
AB  - A total of 97 patients with hepatic hydatid cysts were examined and surgically
      treated over a period of 4 years. All patients, most of whom (86; 89%) were
      female, presented with upper abdominal swellings. Ultrasonography was of great
      value in confirming the diagnosis in all cases. All the hydatid cysts were
      treated with minimal surgical interference and the residual cavities were drained
      after surgery. Formalin (0.5%), the only scolicidal agent available in Yemen, was
      used in 73 cases of the series. There were no deaths and no recurrences.

PMID- 1383516
TI  - Management of perianal sepsis in a district general hospital.
AB  - Perianal sepsis remains a common surgical problem. A total of 121 patients
      undergoing surgery for perianal abscess and/or fistulae over a 2-year period was
      studied. Of these, 50 patients (41.3%) had suffered from previous perianal sepsis
      (not necessarily resulting in hospital attendance). Ninety-one patients underwent
      incision and drainage of abscesses (ischiorectal and perianal) for the first
      time, whereas eight patients underwent drainage of recurrent abscesses. Fistulae
      were identified when the abscess was drained in 14 of 91 patients, and a further
      ten patients subsequently developed fistulae. Twenty-two patients presented with
      a discharging fistula. A high yield of bowel organisms was present in patients
      with coexisting fistulae (88%), recurrent abscesses (75%) and in those who
      subsequently developed fistulae (83%). We confirm that such a growth can be used
      to identify patients who will benefit from further examinations.

PMID- 1383517
TI  - Colorectal surgeons in district general hospitals produce similar survival
      outcomes to their teaching hospital colleagues: review of 5-year survivals in
      Manchester.
AB  - A study of 578 patients treated for colorectal cancer in the North-west region
      comparing survival after surgery in teaching and non-teaching hospitals was
      performed. All patients had a minimum of 5 years follow-up. A greater proportion
      of elderly and emergency patients were treated in the non-teaching hospitals. The
      number of operative mortalities and 5-year survival figures for all causes of
      death and for colorectal deaths alone were similar in teaching and non-teaching
      hospital patients.

PMID- 1383518
TI  - C-reactive protein in the differential diagnosis of the acute abdomen, especially
      acute appendicitis.
AB  - Serum C-reactive protein (CRP) was qualitatively determined before surgery in 189
      patients undergoing appendicectomy. The sensitivity, specificity, negative
      predictive value and overall accuracy of CRP were assessed: CRP had a high
      specificity (76.3%) but a sensitivity of only 39.7%. CRP may be of value in the
      assessment of acute abdominal pain, by helping to exclude from surgery those
      patients with normal appendices.

PMID- 1383519
TI  - Quality and interpretation of operative cholangiography in a district general
      hospital.
AB  - The quality and interpretation of operative cholangiography were assessed in 128
      patients undergoing cholecystectomy. The quality of each cholangiogram was
      assessed by calculating a cholangiogram score according to the anatomical
      structure visualized. Out of a maximum possible score of 5, 26% of cholangiograms
      achieved a score of less than or equal to 3 and were considered as technical
      failures. The sensitivity, specificity and negative predictive values regarding
      the surgeon's interpretation of the cholangiograms were high and compared well
      with the radiologist's assessment. However, the positive predictive value for the
      surgeon's assessment of the cholangiograms was 74% compared with 95% for the
      radiologist (P less than 0.02). Improvement in cholangiography can only be
      achieved by greater attention to detail and perseverance. After an adequate
      examination, the only criteria for common bile duct exploration should be the
      presence of filling defect(s).

PMID- 1383520
TI  - A drip is unnecessary after cholecystectomy.
AB  - A randomized controlled study of 93 patients undergoing a cholecystectomy was
      performed to examine the need for intravenous fluids in the postoperative period.
      Forty-five patients were randomized to have only oral fluid, and these patients
      suffered significantly less in the way of haemodilution as measured by changes in
      packed cell volume (P = 0.0001), haemoglobin (P = 0.0001) and urea (P = 0.036)
      than those who routinely received intravenous fluids. Although questionnaires at
      the time of discharge showed that patients themselves did not object to an
      intravenous infusion, recent studies linking deep vein thromboses to
      haemodilution, coupled with the findings presented here, provide an argument
      against their routine and often unconsidered use.

PMID- 1383521
TI  - Colorectal cancer in South Tyneside: a personal audit.
AB  - A detailed retrospective audit over a 10-year period of 162 patients presenting
      with colorectal cancer to one surgeon without a specific interest in colorectal
      surgery was undertaken. The modes of presentation and potential sources of delay
      in treatment were analysed. The 30-day hospital mortality rate was 10.1% and most
      of these patients had incurable disease. The crude survival 1 year after the
      study was 34% (mean follow-up 6 years); at 3 years after study, it was the same
      (8 years mean follow-up). Survival data are also given in relation to the
      presentation, and operative and histological findings. Preoperative radiotherapy
      for rectal cancers is discussed and assessed. During the last 3 years, 49 further
      patients have presented. The operative mortality rate was 8%. It is suggested
      that improved surgical treatment, particularly in the acute case, has been
      responsible for the reduced mortality rate. Only 51% of patients underwent
      operation with a reasonable prospect of cure. It is suggested that no improvement
      in the prospects of patients with colorectal cancer will occur until pre-symptom
      diagnosis from screening techniques is more commonly available.

PMID- 1383522
TI  - Repeat hepatic resection for metachronous carcinoma of the liver.

PMID- 1383524
TI  - Management of immunosuppression in renal transplant patients with septicaemia.

PMID- 1383523
TI  - Aortoappendiceal fistula: a case report.

PMID- 1383525
TI  - Hypothermia and the crush syndrome.

PMID- 1383526
TI  - A new way to tie the surgeon's knot.

PMID- 1383527
TI  - Partial weight bearing after operations for hip fractures in elderly patients.
AB  - Factors affecting a patient's ability to carry out partial weight bearing after
      operation for hip fracture were studied in 100 patients. Seventy-six were able to
      do so. Significant factors included the muscle power of the good limbs and the
      mental state, whereas age, body-weight and type of operation were not
      significant. Logistical regression analysis showed that it was possible to
      predict a patient's partial weight bearing potential by simply testing the left
      hand grip and the 'Set' test score.

PMID- 1383528
TI  - Treatment of undisplaced subcapital fractures.
AB  - A total of 157 patients with undisplaced subcapital fractures was studied with
      reference to outcome depending on the method of treatment; 135 were treated
      surgically and 22 were treated conservatively. The main complication of treatment
      was non-union, with an overall incidence of 5.7%. Conservative treatment resulted
      in an incidence of non-union which was approximately twice that of patients who
      were treated surgically. Patients treated surgically, however, had significant
      postoperative complications in 14.8% of cases. Although conservative treatment
      has an increased incidence of non-union, it is a safe method of treatment and we
      feel it still has a place in selected patients.

PMID- 1383529
TI  - Trends in infection prophylaxis in orthopaedics.
AB  - The current measures employed by consultant orthopaedic surgeons in Scotland to
      prevent infection were established by postal questionnaire. Our findings were
      compared with those of a similar study carried out 5 years previously. An
      increasing number of surgeons use routine systemic antibiotic prophylaxis for
      total hip arthroplasty (99% versus 91% 5 years ago), in treating compound
      fractures (89% versus 75% 5 years ago) and for internal fixation of closed
      fractures with metal implants (49% versus 12% 5 years ago). Cephalosporins are
      increasingly used as the antibiotic of choice. By starting antibiotics earlier
      than the day of surgery or continuing for more than 24 h after surgery, just over
      half the surgeons questioned administer antibiotics for longer than would seem to
      be necessary for elective surgery.

PMID- 1383530
TI  - Prevertebral haematoma as an inconsistent clue to cervical spine fractures.

PMID- 1383531
TI  - Toxic shock-like syndrome due to streptococcal hand infection.

PMID- 1383532
TI  - Goal posts in total hip replacement: a pelvic alignment device.

PMID- 1383533
TI  - Estimating trauma centre workload.

PMID- 1383534
TI  - Management of mammillary fistulae.

PMID- 1383535
TI  - Endoscopic oesophagectomy through a right thoracoscopic approach.

PMID- 1383536
TI  - Disc battery ingestion: a review and a management plan.

PMID- 1383537
TI  - The beneficial effect of dextran on anastomotic patency and flap survival in a
      strongly thrombogenic model.
AB  - Dextran lowers the probability of thrombus formation, by reducing platelet
      aggregation and adhesion and by increasing fibrinolysis. All studies to date
      using dextran for microvascular reconstruction have examined only short-term (1
      to 2 hr) patency in isolated vessels. The current study used an established
      thrombotic model (inverted sleeve interposition graft), to investigate the effect
      of dextran on the long-term survival of pedicle flaps. A6- x 3-cm epigastric flap
      was elevated. A 2-mm inverted sleeve interposition graft was placed on the artery
      side of the pedicle by microvascular techniques. One group received dextran (17
      cc/kg) 2 hr preoperatively and every 6 hr postoperatively for the next 72 hr. A
      control group received saline on the same schedule. Survival was assessed on
      postoperative day 7, at which time necrosis was obvious. Several parameters
      (clotting studies and electron microscopy) were studied to characterize the
      phenomenon more clearly. Only 25 percent of saline-treated flaps survived (2/8),
      while all dextran-treated flaps survived (7/7) (p less than 0.02, Fisher exact
      test). Thus, dextran allowed flaps to survive by preventing thrombus formation,
      despite a strong thrombogenic focus.

PMID- 1383538
TI  - Neurotrophic factors: role in peripheral neuron survival and axonal repair.

PMID- 1383539
TI  - Distinction between true acrosome reaction and degenerative acrosome loss by a
      one-step staining method using Pisum sativum agglutinin.
AB  - When western blots of human sperm proteins solubilized by acid extraction
      (presumably mainly acrosomal proteins) or by sodium dodecyl sulfate (SDS) were
      probed with biotin-conjugated Pisum sativum agglutinin (PSA), distinct sets of
      proteins were labelled in both preparations. When smears of human spermatozoa
      were treated with methanol either for 30 s or for 15 min and then exposed to FITC
      conjugated PSA, the resulting fluorescence pattern essentially depended on the
      time of methanol treatment. With the longer treatment, fewer spermatozoa showed
      selective acrosomal labelling and more were labelled uniformly throughout,
      without a clear predilection for a single sperm region. With the shorter time of
      methanol treatment, the poorly topographically differentiated, whole-cell
      labelling was typical of dead spermatozoa as confirmed by a close correlation
      between the percentages of spermatozoa showing this type of labelling and of
      those stained supravitally with Hoechst 33258. The preferential whole-cell
      labelling of dead spermatozoa with PSA is considered to be due to increased
      availability of the nonacrosomal set of PSA-reactive sites in dead spermatozoa
      after a short treatment with methanol, whereas this treatment is probably not
      sufficient to expose most of these sites when applied to living spermatozoa. The
      simplicity of the staining protocol makes this method feasible in routine work in
      a number of clinical and research applications.

PMID- 1383540
TI  - Genes encoding the alpha and beta chains of follicle-stimulating hormone are not
      sites for the Booroola (FecB) mutation in sheep.
AB  - Bovine cDNA probes for the beta-subunit of follicle-stimulating hormone beta (FSH
      beta) and the alpha-subunit of the glycoprotein hormones identify genetic
      variation (polymorphic restriction fragments) near these genes in sheep. The
      inheritance of the polymorphic restriction fragments was studied in half-sibling
      pedigrees generated by mating heterozygous (B+) rams to non-carrier (++) ewes so
      that the co-inheritance or genetic linkage to the Booroola (FecB) locus and the
      alpha- and beta-subunits of FSH could be analysed. Genetic recombination was
      observed between the FSH beta locus and the FecB locus in all five families
      studied and between the alpha-subunit and the FecB locus in the two families
      studied. We conclude that the FecB mutation does not lie within the FSH beta- or
      alpha-subunit genes encoding the heterodimeric hormone FSH, and that the high
      concentrations of FSH observed in carrier ewes must result from indirect actions
      of the FecB mutation on the synthesis, processing, storage, release or metabolism
      of FSH.

PMID- 1383541
TI  - Spontaneous reflex sympathetic dystrophy (Sudeck's atrophy) syndrome associated
      with idiopathic thrombocytopenia.
AB  - A 37-year-old woman developed reflex sympathetic dystrophy (RSD) (Sudeck's
      atrophy) syndrome in the right foot. Simultaneously, she had idiopathic
      thrombocytopenia. There was no history of injury or bone fracture before onset of
      RSD. Spontaneous RSD associated with idiopathic thrombocytopenia has rarely been
      described. A possible relationship between the 2 conditions is discussed.

PMID- 1383542
TI  - Innervation of bone from healthy and arthritic rats by substance P and calcitonin
      gene related peptide containing sensory fibers.
AB  - Mechanical stress causes remodelling of bone, a transformation of bone structure
      by physical forces through an unknown mechanism. Inflammation also affects bone
      structure, through altered use and the production of various inflammatory
      mediators. The peripheral nervous system may play both a sensory and an efferent
      role in the mechanical and inflammatory influences on bone structure. We studied
      the occurrence of substance P and calcitonin gene related peptide (CGRP)
      containing nerves in periosteal tissue, bone marrow, diaphysis and epiphysis of
      the ankle and knee joints of healthy and adjuvant arthritic rats. In arthritic
      animals, only ankle joints were affected by the inflammation. The periosteum was
      richly innervated both in healthy and arthritic animals. In arthritic rats few
      nerve fibers penetrated the woven, callous bone underlying the periosteum. Also
      bone marrow contained substance P and CGRP immunoreactive nerves in normal bone,
      whereas the hypercellular bone marrow of arthritic rats showed a decrease in the
      density of substance P and CGRP containing fibers. Epiphysis had a dense
      innervation compared to diaphysis. In contrast to large erosions, small
      peripheral erosions contained some CGRP immunoreactive fibers, perhaps as a sign
      of attempts of reactive repair. Our results suggest a local delivery system of
      potent peptide regulatory factors in bone, a system also affected by the
      pathophysiology of arthritis.

PMID- 1383543
TI  - Digital sympathectomy for refractory Raynaud's phenomenon in an adolescent.
AB  - We describe the case of an adolescent with severe Raynaud's phenomenon refractory
      to conventional medical management. Her course was complicated by fingertip
      ulceration and necrosis. The localized surgical technique of digital
      sympathectomy was successfully used in the management of her disease, and should
      be considered for intractable Raynaud's phenomenon.

PMID- 1383544
TI  - Excitatory amino acid receptor ligands. Synthesis and biological activity of 3
      isoxazolol amino acids structurally related to homoibotenic acid.
AB  - The 3-isoxazolol amino acid (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4
      yl)propionic acid (AMPA, 2) and the isomeric compound (RS)-2-amino-3-(3-hydroxy-4
      methylisoxazol-5-yl)propionic acid (4-methylhomoibotenic acid, 4a) are potent
      agonists at the AMPA subtype of central excitatory amino acid receptors. Using 4a
      as a lead structure, the amino acids 4c-e, in which the 4-methyl group of 4a is
      replaced by substituents of different size and polarity, were synthesized.
      Attempts to synthesize 4-(bromomethyl)homoibotenic acid (4f), a potential
      receptor alkylating agent, were unsuccessful. 4-Butylhomoibotenic acid (4c) and 4
      (2-hydroxyethyl)homoibotenic acid (4e) were equipotent as inhibitors of [3H]AMPA
      binding (IC50 = 2 microM) and showed similar excitatory activity in the rat
      cortical slice preparation. 4d did not show significant affinity for AMPA
      receptor sites, but turned out to be a weak N-methyl-D-aspartic acid (NMDA)
      receptor antagonist. However, like 4c,e, 4d did not significantly affect the
      binding of the competitive NMDA antagonist, [3H]CPP, or the noncompetitive NMDA
      antagonist, [3H]MK-801. None of the amino acids 4c-e showed detectable affinity
      for [3H]kainic acid binding sites. Like the parent compound 4a (IC50 = 0.18
      microM), 4c (IC50 = 0.18 microM), 4e (IC50 = 0.14 microM), and in particular 4d
      (IC50 = 0.02 microM) were effective inhibitors of calcium chloride-dependent
      [3H]glutamic acid binding, whereas AMPA is inactive (IC50 greater than 100
      microM) in this binding assay. Thus, 4d is an effective and highly selective
      inhibitor of calcium chloride-dependent [3H]glutamic acid binding and may be a
      useful tool for studies of the physiological relevance and pharmacological
      importance of this binding affinity.

PMID- 1383545
TI  - Response to Saunders and Singh.

PMID- 1383546
TI  - Identification of a new DMD gene deletion by ectopic transcript analysis.
AB  - The detailed genetic analysis of the Duchenne/Becker muscular dystrophy gene is
      hindered by the large number of exons involved and their separation by huge
      introns. These problems can be overcome by the analysis of mRNA rather than
      genomic DNA and ectopic transcripts derived from peripheral blood lymphocytes
      provide a convenient source of material. Using reverse transcription and nested
      PCR, we show here a comprehensive strategy for the rapid and complete analysis of
      the coding sequences from complex genes and illustrate its potential by the
      identification of a hitherto undescribed single exon deletion.

PMID- 1383547
TI  - Shared antigenic epitopes of the major core proteins of human and simian
      immunodeficiency virus isolates.
AB  - Antigenic epitopes on the major core (gag) protein of isolates of simian and
      human immunodeficiency virus (SIV and HIV) were compared using a panel of eleven
      mouse monoclonal antibodies (Mabs) that recognized nine distinct gag epitopes.
      Viral isolates used for comparison were HIV-1IIIb, HIV-2ROD, and SIV isolates
      from macaque (SIVmac), sooty mangabey (SIVsm-UCD), African green monkey (SIVagm),
      and stump-tailed macaque (SIVstm-UCD). The relatedness of the various HIV and SIV
      isolates, as determined by Mabs to core protein epitopes, paralleled that
      ascertained by genetic sequencing.

PMID- 1383548
TI  - Outwardly rectifying chloride channels in lymphocytes.
AB  - Outwardly rectifying Cl- channels in cultured human Jurkat T-lymphocytes were
      activated by excising a patch of membrane using the inside-out (i/o) patch-clamp
      configuration and holding at depolarized voltages for prolonged periods of time
      (1-6 min at +80 mV, 20 degrees C). The single-channel current at +80 mV was 4.5
      +/- 0.3 pA and at -80 mV, it was 1.0 +/- 0.4 pA. After activation, the
      probability of being open (Po) for the lymphocyte channel was voltage
      independent. Activation of the Cl- channel in lymphocytes was temperature
      dependent. Nineteen percent of i/o recordings from lymphocytes made at 20 degrees
      C exhibited Cl- channel activity. In contrast, 49% of recordings made at 30
      degrees C showed channel activity. The number of channels in an active patch was
      not significantly different at the two temperatures. Channel activation in
      excised, depolarized patches also occurred 20-fold faster at 30 degrees C than at
      20 degrees C. There was no marked change in the single-channel conductance at 30
      degrees C. Open-channel conductance was blocked by 200 microM indanyloxyacetic
      acid (IAA) or 1 mM SITS when applied to the intracellular side of the patch. The
      characteristics of this channel are similar to epithelial outwardly rectifying Cl
      channels thought to be involved in fluid secretion.

PMID- 1383549
TI  - Cell swelling activates K+ and Cl- channels as well as nonselective, stretch
      activated cation channels in Ehrlich ascites tumor cells.
AB  - Cell-attached patch-clamp recordings from Ehrlich ascites tumor cells reveal
      nonselective cation channels which are activated by mechanical deformation of the
      membrane. These channels are seen when suction is applied to the patch pipette or
      after osmotic cell swelling. The channel activation does not occur
      instantaneously but within a time delay of 1/2 to 1 min. The channel is permeable
      to Ba2+ and hence presumably to Ca2+. It seems likely that the function of the
      nonselective, stretch-activated channels is correlated with their inferred Ca2+
      permeability, as part of the volume-activated signal system. In isolated inside
      out patches a Ca(2+)-dependent, inwardly rectifying K+ channel is demonstrated.
      The single-channel conductance recorded with symmetrical 150 mM K+ solutions is
      for inward current estimated at 40 pS and for outward current at 15 pS.
      Activation of the K+ channel takes place after an increase in Ca2+ from 10(-7) to
      10(-6) M which is in the physiological range. Patch-clamp studies in cell
      attached mode show K+ channels with spontaneous activity and with characteristics
      similar to those of the K+ channel seen in excised patches. The single-channel
      conductance for outward current at 5 mM external K+ is estimated at about 7 pS. A
      K+ channel with similar properties can be activated in the cell-attached mode by
      addition of Ca2+ plus ionophore A23187. The channel is also activated by cell
      swelling, within 1 min following hypotonic exposure. No evidence was found of
      channel activation by membrane stretch (suction). The time-averaged number of
      open K+ channels during regulatory volume decrease (RVD) can be estimated at 40
      per cell. The number of open K+ channels following addition of Ca2+ plus
      ionophore A23187 was estimated at 250 per cell. Concurrent activation in cell
      attached patches of stretch-activated, nonselective cation channels and K+
      channels in the presence of 3 mM Ca2+ in the pipette suggests a close spatial
      relationship between the two channels. In excised inside-out patches (with NMDG
      chloride on both sides) a small 5-pS chloride channel with low spontaneous
      activity is observed. The channel activity was not dependent on Ca2+ and could
      not be activated by membrane stretch (suction). In cell-attached mode single
      channel currents with characteristics similar to the channels seen in isolated
      patches are seen. In contrast to the channels seen in isolated patches, the
      channels in the cell-attached mode could be activated by addition of Ca2+ plus
      ionophore A23187.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1383550
TI  - Ro ribonucleoprotein assembly in vitro. Identification of RNA-protein and protein
      protein interactions.
AB  - The human Y RNAs, small RNAs with an unknown function, are complexed with at
      least three proteins: the 60,000 M(r) Ro protein (Ro60), the 52,000 M(r) Ro
      protein (Ro52) and the La protein (La). In this study we examined the
      intermolecular interactions between the components of these so-called Ro
      ribonucleoprotein (Ro RNP) complexes. Incubation of 32P-labelled hY1 RNA in HeLa
      S100 extract allows the reconstitution of Ro RNP complexes, which were analysed
      by immunoprecipitation with monospecific antisera. By immunodepletion of HeLa
      S100 extracts for either Ro60, Ro52 or La, followed by supplementation with
      recombinant Ro60 or La, it was demonstrated that both Ro60 and La bind to hY1 RNA
      directly without being influenced by one of the other proteins. However, binding
      of Ro52 to hY1 RNA required the presence of Ro60, which strongly suggests that
      the association of Ro52 with Ro RNPs is mediated by protein-protein interactions
      between Ro60 and Ro52.

PMID- 1383551
TI  - Domains of the Escherichia coli threonyl-tRNA synthetase translational operator
      and their relation to threonine tRNA isoacceptors.
AB  - The expression of the gene for threonyl-tRNA synthetase (thrS) is negatively
      autoregulated at the translational level in Escherichia coli. The synthetase
      binds to a region of the thrS leader mRNA upstream from the ribosomal binding
      site inhibiting subsequent translation. The leader mRNA consists of four
      structural domains. The present work shows that mutations in these four domains
      affect expression and/or regulation in different ways. Domain 1, the 3' end of
      the leader, contains the ribosomal binding site, which appears not to be
      essential for synthetase binding. Mutations in this domain probably affect
      regulation by changing the competition between the ribosome and the synthetase
      for binding to the leader. Domain 2, 3' from the ribosomal binding site, is a
      stem and loop with structural similarities to the tRNA(Thr) anticodon arm. In
      tRNAs the anticodon loop is seven nucleotides long, mutations that increase or
      decrease the length of the anticodon-like loop of domain 2 from seven nucleotides
      abolish control. The nucleotides in the second and third positions of the
      anticodon-like sequence are essential for recognition and the nucleotide in the
      wobble position is not, again like tRNA(Thr). The effect of mutations in domain 3
      indicate that it acts as an articulation between domains 2 and 4. Domain 4 is a
      stable arm that has similarities to the acceptor arm of tRNA(Thr) and is shown to
      be necessary for regulation. Based on this mutational analysis and previous
      footprinting experiments, it appears that domains 2 and 4, those analogous to
      tRNA(Thr), are involved in binding the synthetase which inhibits translation
      probably by interfering with ribosome loading at the nearby translation
      initiation site.

PMID- 1383552
TI  - Determination of a high-quality nuclear magnetic resonance solution structure of
      the bovine pancreatic trypsin inhibitor and comparison with three crystal
      structures.
AB  - A high-quality three-dimensional structure of the bovine pancreatic trypsin
      inhibitor (BPTI) in aqueous solution was determined by 1H nuclear magnetic
      resonance (n.m.r.) spectroscopy and compared to the three available high
      resolution X-ray crystal structures. A newly collected input of 642 distance
      constraints derived from nuclear Overhauser effects and 115 dihedral angle
      constraints was used for the structure calculations with the program DIANA,
      followed by restrained energy minimization with the program AMBER. The BPTI
      solution structure is represented by a group of 20 conformers with an average
      root-mean-square deviation (RMSD) relative to the mean solution structure of 0.43
      A for backbone atoms and 0.92 A for all heavy atoms of residues 2 to 56. The
      pairwise RMSD values of the three crystal structures relative to the mean
      solution structure are 0.76 to 0.85 A for the backbone atoms and 1.24 to 1.33 A
      for all heavy atoms of residues 2 to 56. Small local differences in backbone atom
      positions between the solution structure and the X-ray structures near residues
      9, 25 to 27, 46 to 48 and 52 to 58, and conformational differences for individual
      amino acid side-chains were analyzed for possible correlations with
      intermolecular protein-protein contacts in the crystal lattices, using the
      pairwise RMSD values among the three crystal structures as a reference.

PMID- 1383553
TI  - Gene structure of human CD59 and demonstration that discrete mRNAs are generated
      by alternative polyadenylation.
AB  - We have isolated the CD59 gene from human genomic libraries. The gene is
      distributed over more than 27 x 10(3) base-pairs and consists of one 5'
      untranslated exon and three coding exons. The gene structure is similar to that
      of mouse Ly-6 with the exception of the larger size of CD59 introns. Northern
      blot analysis using six different probes located in the 3'-region of the gene
      shows that more than four different CD59 mRNA molecules are generated by
      alternative polyadenylation. Three of these polyadenylation sites were predicted
      from previously published cDNA sequences. We have isolated a fourth from Jurkat
      poly(A)+ RNA by the procedure of rapid amplification of cDNA ends. Alternative
      polyadenylation may be due to the RNA secondary structure around the typical
      polyadenylation signal, AAUAAA.

PMID- 1383554
TI  - Neuronal maps of the frontal ganglion of the cockroach, Periplaneta americana,
      prepared by heavy metal iontophoresis.
AB  - Neurons in whole mount preparations of the frontal ganglion (FG) of the
      cockroach, Periplaneta americana, were mapped with the aid of cobalt chloride
      staining and silver intensification techniques. Eighty-six neurons were counted
      in the FG after staining with reduced methylene blue. The cell size ranged
      between 20 to 35 microns in diameter. Of the somata located in the FG, 44 were
      found to contribute their fibers to the nervus recurrens, 26 to the right frontal
      commissure, 28 to the left frontal commissure, and 6 to the nervus connectivus.
      In addition, a few neurons presumably from the tritocerebral region also
      contribute their fibers in the formation of nervus connectivus. The present study
      has helped delineate the neuronal connections of the FG with the brain and
      neuroendocrine system (corpora cardiaca and corpora allata). This information
      will be useful in facilitating the positioning of microelectrodes in our future
      electrophysiological experiments.

PMID- 1383556
TI  - The response of rubrospinal neurons to axotomy at different stages of development
      in the North American opossum.
AB  - Rubral axons can grow around a lesion of their pathway in the thoracic spinal
      cord of developing opossums and a critical period exists for that plasticity. The
      critical period probably begins when rubral axons first grow into the thoracic
      cord, and it extends until approximately postnatal day 30. We previously noted
      that most rubrospinal neurons die after transection of their axon during the
      critical period, suggesting that plasticity results primarily from growth of
      axons not damaged by the lesion (Xu and Martin, J. Comp. Neurol. 279, 368-381,
      1989). That observation led us to study the response of rubrospinal neurons to
      axotomy in more detail and at additional stages of development, using a
      prelabeling paradigm. We first injected fast blue (FB) into the caudal thoracic
      or rostral lumbar spinal cord in animals ranging from estimated postnatal day 9
      to 50 and, about 4 days later, lesioned the rubrospinal tract several segments
      rostral to the injection. Approximately 30 days later, the animals were killed so
      that the red nucleus could be searched for labeled neurons. During the critical
      period for plasticity, rubrospinal neurons showed signs of degeneration 1 week
      after their axon was cut. When animals were killed 2-3 weeks after lesioning,
      there was an obvious decrease in axotomized neurons within the red nucleus, and
      by 4 weeks, more than 75% of them had degenerated. The marked susceptibility of
      rubrospinal neurons to axotomy during the critical period for plasticity is
      consistent with the hypothesis that developmental plasticity of the rubrospinal
      tract results primarily from growth of axons that were not damaged by the lesion.
      Our results also suggest that survival of axotomized rubrospinal neurons
      increases with age.

PMID- 1383555
TI  - The loading of fura-2 into mitochondria in the intact perfused rat heart and its
      use to estimate matrix Ca2+ under various conditions.
AB  - When rat hearts were perfused with a medium containing 10 microM fura-2/AM for 1
      hr at 37 degrees C a significant amount of the derived fura-2 could be detected
      in subsequently isolated mitochondria. This procedure allowed the measurement of
      matrix free Ca2+ concentration ([Ca2+]m) of mitochondria rapidly isolated from
      whole hearts by a method which avoids artefactual redistribution of Ca2+. [Ca2+]m
      in mitochondria prepared from control hearts and incubated with respiratory
      substrates and EGTA was found to be 172 +/- 23 nM (mean +/- S.E.M.). When hearts
      were subjected to either increased mechanical work or treatment with 1 microM L
      epinephrine (for 2 mins) [Ca2+]m increased to 916 +/- 138 nM and 727 +/- 65 nM
      respectively. The presence of ruthenium red (2.5 microM) in the perfusion medium
      prior to and during inotropic intervention diminished these increases in
      [Ca2+]m(to 316 +/- 28 nM and 218 +/- 18 nM respectively) but did not affect
      control values. Addition of Na+ ions to incubated mitochondria to enhance
      mitochondrial Ca2+ egress diminished these increases in [Ca2+]m due to pre
      treatment with positive inotropes (compared to controls). These changes in
      [Ca2+]m were broadly parallelled by changes in the active non-phosphorylated form
      of pyruvate dehydrogenase (PDH) under all circumstances. These results provide
      further evidence that the activation of PDH by positive inotropes is accomplished
      by, and at least in part due to, raised mitochondrial matrix free [Ca2+] and that
      such increases can be maintained in isolated and suitably incubated mitochondria.

PMID- 1383558
TI  - Axons modulate the expression of proteolipid protein in the CNS.
AB  - We examined the expression of mRNA encoding proteolipid protein (PLP), the major
      myelin protein in the CNS, in developing rat cerebrum, and in normal and
      degenerating optic nerves. PLP transcripts were initiated at two clusters of
      start sites that were separated by about 30 base pairs. During the peak of PLP
      mRNA expression in developing cerebrum, a higher proportion of PLP transcripts
      were initiated from the distal start site, furthest from the open reading frame,
      than in mature cerebrum. We enucleated one eye of immature rats to cause
      Wallerian degeneration in the optic nerve. In these degenerating optic nerves,
      the steady state levels of PLP mRNA fell markedly, and the proportion of distally
      initiated PLP transcripts declined to the same proportion found in normal adult
      nerves. Changes in myelin gene expression were not limited to PLP mRNA, as the
      steady-state levels of myelin basic protein (MBP) mRNA paralleled those of PLP
      mRNA in the developing cerebrum and in degenerating optic nerves. Thus,
      oligodendrocytes require axons to maintain their normal levels of PLP and MBP
      transcripts and the high proportion of distally initiated PLP transcripts that
      characterize early myelination.

PMID- 1383557
TI  - Toxicity to rats of methanol-fueled engine exhaust inhaled continuously for 28
      days.
AB  - Fischer 344 rats were exposed to three concentrations of exhaust generated by an
      M85 methanol-fueled engine (methanol with 15% gasoline) without catalyst for 8
      h/d, 7 d/wk for 7, 14, 21, or 28 d. Concentration- and time-dependent yellowing
      of the fur was prominent in all treated groups. Concentration-dependent increases
      in the erythrocyte count, hematocrit, hemoglobin concentration, formaldehyde in
      plasma, and carboxyhemoglobin in the erythrocytes, and decrease in serum alkaline
      phosphatase activity were seen after all exposure periods. Histopathologically,
      lesions were found in the nasal cavity and lungs after 7 d of exposure. Squamous
      metaplasia of the respiratory epithelium of level 1 (level of the posterior edge
      of the upper incisor teeth) lining of the nasoturbinate and/or maxilloturbinate
      and infiltration of neutrophils into the submucosa, and decreases of Clara cells
      in the terminal bronchiolus and of cilia in the bronchiolar epithelium, were
      observed in the high-concentration group (carbon monoxide, 94 ppm; formaldehyde,
      6.9 ppm; methanol, 17.9 ppm; nitrogen oxides, 52.7 ppm; nitrogen dioxide, 10.6
      ppm). The histopathological extents of several lesions increased slightly with
      the exposure time. Slight squamous metaplasia and hyperplasia of the respiratory
      epithelium at level 1 were also observed in the medium-concentration group (one
      in three of the high-concentration group). No histopathological changes were
      found in the olfactory epithelium of the nasal cavity. In the low-concentration
      group (one in nine of the high-concentration group), no marked histopathological
      changes in these organs were observed. These results may suggest that the lesions
      observed in the nasal cavity of rats exposed to methanol-fueled engine exhaust
      were mainly caused by formaldehyde, although other components in the exhaust also
      may have affected nasal cavity and/or lungs to less extent.

PMID- 1383559
TI  - Interaction between oligodendroglia and immune cells: mitogenic effect of an
      oligodendrocyte precursor cell line on syngeneic T lymphocytes.
AB  - We analyzed cellular interactions between T lymphocytes and a recently
      established immortal glial line, L3 that retains several properties of immature
      oligodendrocytes (Aloisi et al., J Neurosci Res 27:16-24, 1990). L3
      oligodendrocytes (L3-OL) cannot be induced to express class II antigens, nor do
      they specifically present antigen to syngeneic specific T lymphocyte. However, L3
      OL strongly enhance the proliferation of freshly activated, interleukin-2(IL-2)
      dependent T-line lymphocytes and concanavalin A (ConA)-activated lymphoblasts,
      irrespective of their antigen specificity or surface phenotype (CD4+ or CD8+).
      Resting and some activated T cells were susceptible to the mitogenic effect of L3
      OL only in the presence of exogenous IL-2, not of other cytokines. The mitogenic
      effect of L3-OL did not depend on cell viability. It was observed in
      paraformaldehyde-fixed L3-OL cells and in membrane preparations, but not in
      culture supernatant. Neither intact L3-OL cells nor membrane preparations had
      direct IL-2 activity. The conclusion that the mitogenic effect of L3-OL cells is
      exerted by membrane structures acting as a costimulatory factor(s) of IL-2 is
      supported by the finding that it is largely blocked by a monoclonal anti-IL-2
      receptor antibody. The effect is distinct from membrane-bound IL-1, membrane
      bound tumor necrosis factor-alpha (TNF-alpha), IL-3, or IL-6 and cannot be
      reconstituted by these cytokines.

PMID- 1383560
TI  - AP-1 complex and c-fos transcription are involved in TPA provoked and trans
      synaptic inductions of the tyrosine hydroxylase gene: insights into long-term
      regulatory mechanisms.
AB  - We have previously shown that the phorbol ester, TPA, which activates protein
      kinase C, causes, in PC12 cells, a transcriptional activation of tyrosine
      hydroxylase (TH), the key enzyme in catecholamine synthesis. The study has now
      been extended to examine the processes that underlie this transcriptional
      stimulation and, in addition, to seek whether similar mechanisms are involved in
      long-term trans-synaptic induction of the TH gene in adrenal medullae of rats
      that have been given a single injection of reserpine. In both systems, it was
      found that the induction of c-fos gene transcription was associated with that of
      the TH gene but with different kinetics. The promoter of the TH gene contains (at
      position -207/-200) a sequence (TGATTCA) which differs from the consensus TRE or
      AP-1 site (TGACTCA) by one nucleotide. Experiments were carried out to
      investigate whether the AP-1 protein complex which is known to contain Fos and
      Jun binds to the putative TRE region of the TH promoter. In the gel shift assays,
      the nuclear protein extracts derived from TPA-treated PC12 cells and from AM of
      reserpine injected rats displayed a higher magnitude of binding to a 25-mer TRE
      TH oligonucleotide as compared to controls. The results showed that the behaviour
      of TRE-TH was atypical in that two retarded complexes (A and B) were observed,
      which were displaced by specific competitors. Trans-activation experiments with
      plasmids TRE-TH/TK/CAT and -754/-19 TH/pUC18-CAT in PC12 cells showed an increase
      in CAT activity in response to TPA that correlates with the previously observed
      increase in TH transcriptional activity by TPA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383561
TI  - The nonmyristylated Pr160gag-pol polyprotein of human immunodeficiency virus type
      1 interacts with Pr55gag and is incorporated into viruslike particles.
AB  - The expression of the pol gene of human immunodeficiency virus type 1 occurs via
      a ribosomal frameshift between the gag and pol genes. The resulting protein, a
      Gag-Pol polyprotein, is produced at a level 5 to 10% of that of the Gag protein.
      The Gag-Pol polyprotein is incorporated into virions and provides viral protease,
      reverse transcriptase, and integrase, which are essential for infectivity. It is
      generally believed that the Gag-Pol polyprotein is incorporated into virions via
      interaction with the Gag protein, although the details of the mechanism are
      unknown. To further study this problem, we have constructed a human
      immunodeficiency virus type 1 proviral genome which overexpresses the Gag-Pol
      polyprotein (Pr160gag-pol). Transfection of this proviral genome (pGPpr-) into
      COS-1 cells resulted in the expression of full-length Pr160gag-pol polyprotein.
      Although the majority of the Pr160gag-pol was confined to the cells, low levels
      of reverse transcriptase activity were detectable in the cell supernatants. The
      cotransfection of pGPpr- with a second plasmid which expresses only the Pr55gag
      precursor (pGAG) resulted in a significantly higher level of Pr160gag-pol in the
      medium of transfected cells. Sedimentation analysis using sucrose density
      gradients demonstrated that most Pr160gag-pol was found in fractions
      corresponding to the density of virion particles, indicating that the Pr160gag
      pol polyprotein was released in association with a Pr55gag viruslike particle. To
      further characterize the requirements for the release, a mutation was constructed
      to express an unmyristylated Pr160gag-pol polyprotein. Coexpression with Pr55gag
      demonstrated that the unmyristylated Pr160gag-pol was also incorporated into
      virion particles. Subcellular fractionation experiments revealed that the
      distributions of the Pr160gag-polmyr- and Pr160gag-pol in the membrane and
      cytosol were similar under low- or high-ionic-strength conditions. Taken
      together, these results suggest that myristylation of the Pr160gag-pol
      polyprotein is not required for the interaction with the Pr55gag necessary for
      packaging into a viruslike particle.

PMID- 1383562
TI  - Mutagenic analysis of the coronavirus intergenic consensus sequence.
AB  - Previously, a system in which an intergenic region from mouse hepatitis virus
      (MHV) inserted into an MHV defective interfering (DI) RNA led to transcription of
      a subgenomic DI RNA in helper virus-infected cells was established. In the
      present study, a DI cDNA containing one UCUAAAC consensus sequence in the middle
      of the 0.3-kb-long intergenic region located between genes 6 and 7 was
      constructed. From this DI cDNA clone, 21 mutant DI RNAs were constructed so that
      each of the seven consensus sequence nucleotides was changed individually to the
      three alternative bases. These mutants were used to define how changes in the
      integrity of MHV transcription consensus sequence UCUAAAC affected mRNA
      transcription. Except for two mutants with the sequences UGUAAAC and UCGAAAC, all
      of the mutants supported efficient subgenomic DI RNA transcription. This
      indicated that MHV transcription regulation was sufficiently flexible to
      recognize altered consensus sequences. Next, these and other mutants were used to
      examine the leader-body fusion site on the subgenomic DI RNAs. Sequence analysis
      demonstrated that all subgenomic DI RNAs analyzed contained two pentanucleotide
      sequences; the first sequence seemed to be contributed by the leader, and the
      leader-body fusion most likely took place at either the first or the second
      nucleotide of the second sequence. This observation was not consistent with the
      proposed coronavirus transcription model (S. C. Baker and M. M. C. Lai, EMBO J.
      9:4173-4179, 1990) which states that nucleotide mismatch can be corrected by RNA
      polymerase proofreading activity.

PMID- 1383563
TI  - Requirements for strand transfer between internal regions of heteropolymer
      templates by human immunodeficiency virus reverse transcriptase.
AB  - We have examined the ability of the reverse transcriptase (RT) from human
      immunodeficiency virus (HIV) to carry out strand transfer synthesis (i.e.,
      switching of the primer to a new template) from internal regions of natural
      sequence RNA. A 142-nucleotide RNA template (donor) primed with a specific 20
      nucleotide DNA oligonucleotide was used to initiate synthesis. DNA
      oligonucleotides with homology to internal regions of the donor were used as
      acceptors. In this system, HIV RT produced strand transfer products. An HIV RT
      having RNase H depleted to 3% of normal (HIV RTRD) catalyzed the transfer
      reaction inefficiently. An RNase H-minus deletion mutant of murine leukemia virus
      RT was unable to catalyze strand transfer. HIV RTRD, however, efficiently
      catalyzed transfer when Escherichia coli RNase H was included in the reactions,
      while the mutant murine leukemia virus RT was not efficiently complemented by the
      E. coli enzyme. Evidently, RNase H activity enhances, or is required for,
      internal strand transfer. Two acceptors homologous to 27-nucleotide regions of
      the donor, one offset from the other by 6 nucleotides, were tested. The offset
      eliminated a sequence homologous to a prevalent DNA synthesis pause site in the
      donor. Strand transfer to this acceptor was about 25% less efficient, suggesting
      that RT pausing can enhance strand transfer. When the deoxynucleoside
      triphosphates in the reactions were reduced from 50 to 0.2 microM, increasing RT
      pausing, the efficiency of strand transfer also increased. A model for RT
      catalyzed strand transfer consistent with our results is presented.

PMID- 1383564
TI  - Persistence of viral RNA in mouse brains after recovery from acute alphavirus
      encephalitis.
AB  - Little is known about the relationship between recovery from acute viral
      encephalitis and the clearance of viral genetic material from the central nervous
      system. In a mouse model of Sindbis virus encephalitis, we have previously shown
      that clearance of infectious virus is mediated by antibody-induced restriction of
      viral gene expression rather than by cytotoxic destruction of virally infected
      cells. To explore whether Sindbis virus genomes persist in mouse brain after the
      clearance of infectious virus, we used reverse transcriptase-polymerase chain
      reaction amplification methods to detect Sindbis virus RNA in brain samples from
      immunocompetent BALB/c and antibody-treated immunodeficient scid/CB17 mice. RNA
      sequences from both the nonstructural region (NSP1 gene) and structural regions
      (E2 gene) of Sindbis virus were detected in the brains of all BALB/c and antibody
      treated scid mice examined at 1, 2, and 3 months after infection. Additional
      BALB/c mouse brains were also positive at 8, 12, and 17 months after infection.
      To determine whether persistent RNA was capable of resuming unrestricted
      replication in the absence of the continuous presence of antiviral antibodies,
      viral titers were measured in the brains of scid mice at 1, 2, 3, and 6 months
      after antibody treatment. Viral reactivation was seen in scid mice treated with
      hyperimmune serum or a low dose of monoclonal antibody to the E2 envelope
      glycoprotein, but not in mice treated with a high dose of monoclonal antibody to
      E2. Replication of infectious virus isolated from scid mouse brain could be
      restricted by repeat treatment with immune serum, indicating that viral
      reactivation is not due to antibody-escape mutations. These results demonstrate
      that Sindbis virus can persist long term in a nonproductive form in mouse brain
      and suggest that the humoral immune response plays an important role in
      preventing viral reactivation.

PMID- 1383566
TI  - Epitope specificity of protective lactogenic immunity against swine transmissible
      gastroenteritis virus.
AB  - The epitope specificity of the protective immune response against swine
      transmissible gastroenteritis (TGE) has been investigated by using circulating
      and secretory antibodies. This study was carried out with sows vaccinated with
      TGEV or the antigenically related porcine respiratory coronavirus (PRCV). TGEV
      vaccination of sows resulted in greater lactogenic protection of suckling piglets
      against TGEV challenge and a higher secretory immune response than PRCV
      vaccination did. These differences in the immune response were conditioned by the
      route of antigen presentation as a result of the different tropism of each virus.
      Epitopes on S protein, and in particular those contained in its antigenic site.
      A, were more immunogenic than epitopes on N and M proteins in both groups of
      vaccinated sows, as determined by a competitive radioimmunoassay. Minor
      differences in antibody response against the previously defined antigenic
      subsites Aa, Ab, and Ac were also detected, with subsite Ab being the most
      antigenic in both TGEV- and PRCV-immune sows. These findings suggest that
      antigenic site A on S protein, involved in virus neutralization, is the
      immunodominant site in pregnant sows that confer lactogenic protection. They also
      validate, in experiments with secretory antibodies, the antigenic maps made with
      murine monoclonal antibodies. Therefore, this antigenic site should be considered
      for vaccine or diagnostic development.

PMID- 1383565
TI  - Equine herpesvirus 1 glycoprotein D: mapping of the transcript and a
      neutralization epitope.
AB  - Studies with molecular and immunological techniques identified and mapped the
      transcript encoding glycoprotein D (gD) of equine herpesvirus 1 KyA, as well as
      two continuous gD antigenic determinants. Three mRNA species of 5.5, 3.8, and 1.7
      kb overlap the gD open reading frame and are transcribed from the DNA strand
      encoding gD. Northern (RNA) blot hybridization with both DNA clones and
      riboprobes, as well as S1 nuclease analyses, showed the 3.8-kb mRNA to encode gD
      and to be synthesized as a late (beta-gamma) transcript. The 3.8-kb gD mRNA
      initiates within the US segment 91 and 34 nucleotides downstream of the CCAAT and
      TATA elements, respectively, and encodes a potential polypeptide of 392 amino
      acids. The termination site of this transcript maps within the terminal repeat at
      a site also used by the 5.5-kb mRNA and the IR6-encoded 1.2-kb mRNA, such that
      these three transcripts form a 3'-coterminal nested set. The extended size (2,250
      nucleotides) of the 3' untranslated region of the gD transcript and its
      termination within the terminal repeat may result from the deletion of 3,859 bp,
      which eliminates two consensus polyadenylation signals downstream of the gD open
      reading frame of EHV-1 KyA. Use of antisera to synthetic peptides of 19 amino
      acids (residues 4 to 22) and 20 amino acids (residues 267 to 285) in Western
      immunoblot analyses revealed that gD is present in EHV-1 virions as a 55-kDa
      polypeptide. In addition, these antisera detected the 55-kDa protein as well as
      58- and 47-kDa polypeptides in infected-cell extracts at late times of infection.
      Residues 4 to 22 make up a continuous neutralizing epitope of gD, since
      incubation of equine herpesvirus 1 with the anti-19-mer serum prior to infection
      results in reduced numbers of plaques and reduced levels of virus-encoded
      thymidine kinase. Complement is not required for neutralization mediated by the
      anti-19-mer serum.

PMID- 1383567
TI  - A synthetic peptide to the E glycoprotein of Murray Valley encephalitis virus
      defines multiple virus-reactive T- and B-cell epitopes.
AB  - Synthetic peptides from the envelope glycoprotein sequence of Murray Valley
      encephalitis (MVE) virus were previously evaluated in various strains of mice for
      both the induction of antibody and the in vitro proliferation of peptide-primed T
      helper (Th) cells. MVE peptide 6 (amino acids 230 to 251) elicited reciprocal Th-
      and B-cell reactivity with native MVE virus after primary inoculation of C57BL/6
      mice. In this study, we prepared overlapping subunit peptides of MVE peptide 6
      and evaluated their immunogenicity. Analysis of these peptides delineated at
      least two B-cell epitopes that induced antibody reactive with MVE and other
      Japanese encephalitis serocomplex viruses. This antibody at low titer neutralized
      MVE virus. Genetic restriction of the antibody response to various T-cell
      elements within peptide 6 was observed in C3H, BALB/c, C57BL/6, and B10 congenic
      mice. One element demonstrable after primary immunization, located in the carboxy
      terminus, associated only with major histocompatibility complex class II IAb and
      IAbiEk glycoproteins. Functional stimulation with the peptides in association
      with IAkIEk and IAdIEd molecules was observed only after in vivo secondary
      stimulation. Peptide 6-1 (amino acids 230 to 241) was nonimmunogenic but could be
      recognized by Th cells from peptide 6-immunized mice. Further association of
      peptide 6 with the IAkIEk and IAdIEd subregions was demonstrated by the finding
      that T cells from MVE peptide 6-inoculated C3H and BALB/c mice primed for an
      antibody response to MVE virus. These results suggest that the peptide 6
      sequence, which is relatively conserved among a number of flaviviruses, should be
      given consideration when synthetic immunogens for vaccine purposes are designed.

PMID- 1383568
TI  - Monoclonal antibody analysis of neutralization and antibody-dependent enhancement
      of feline infectious peritonitis virus.
AB  - Fifty-four monoclonal antibodies (MAbs) to feline infectious peritonitis virus
      (FIPV) were characterized according to protein specificity, immunoglobulin
      subclass, virus neutralization, reactivity with different coronaviruses, and
      ability to induce antibody-dependent enhancement (ADE) of FIPV infection in
      vitro. The MAbs were found to be specific for one of three structural proteins of
      FIPV. A total of 47 MAbs were specific for the 205-kDa spike protein (S), 3 MAbs
      were specific for the 45-kDa nucleocapsid protein (N), and 4 MAbs were specific
      for the 26- to 28-kDa membrane protein (M). The S-specific MAbs showed various
      degrees of cross-reactivity with strains of FIPV, feline enteric coronavirus,
      canine coronavirus, and porcine transmissible gastroenteritis virus. Nineteen S
      specific MAbs neutralized FIPV. A total of 15 of the neutralizing MAbs induced
      ADE, and all but 1 were of the immunoglobulin G2a subclass. The remaining four
      neutralizing MAbs that did not induce ADE were of the immunoglobulin G1 subclass.
      Two S-specific MAbs induced ADE but were nonneutralizing. None of the N- or M
      specific MAbs was neutralizing or induced ADE. On the basis of the reactivity
      patterns of the MAbs with FIPV and related coronaviruses, it was concluded that
      there is a minimum of five neutralizing sites on S. In most instances,
      neutralizing MAbs were able to induce ADE, demonstrating a direct relationship
      between neutralization and enhancement. The difference in immunoglobulin subclass
      between neutralizing MAbs that induced ADE and those that did not induce ADE
      suggests that there may be a restriction in the immunoglobulin subclasses capable
      of mediating ADE.

PMID- 1383569
TI  - Design of high-affinity major histocompatibility complex-specific antagonist
      peptides that inhibit cytotoxic T-lymphocyte activity: implications for control
      of viral disease.
AB  - Cytotoxic T lymphocytes (CTLs) recognize viral antigens presented by infected
      cells in the context of their major histocompatibility complex glycoproteins. The
      irreversible killing of virus-infected cells by virus-specific CTLs can be the
      cause of serious disease, particularly in the central nervous, hepatic, and
      cardiovascular systems. Design of molecules controlling (blocking) interaction
      between CTLs and infected cells, and their further use to inhibit (or antagonize)
      T-lymphocyte activity, is an important pharmacologic goal. In this report, we
      describe the design of a new family of peptides which selectively inhibit
      activity of lymphocytic choriomeningitis virus-specific CD8+ T lymphocytes, which
      recognize endogenously processed viral epitopes presented by major
      histocompatibility complex class I molecules.

PMID- 1383570
TI  - Identification of T-cell epitopes on E2 protein of rubella virus, as recognized
      by human T-cell lines and clones.
AB  - T-cell epitopes on the E2 protein of rubella virus were studied by using 15
      overlapping synthetic peptides covering the E2 protein sequence. The most
      frequently recognized epitopes on E2 were E2-4 (residues 54 to 74), with 5 of 10
      tested T-cell lines responding to it. Two CD4+ cytotoxic T-cell cloned isolated
      from one T-cell line responded strongly in proliferation assays with peptide E2-4
      and were cytotoxic to target cells presenting the E2-4 determinant. Truncated
      peptides contained within the E2-4 peptide sequence were used to define the T
      cell determinants. Results indicated that amino acid residues 54 to 65 were
      directly involved. Human cell lines with different HLA phenotypes were tested for
      the capacity to present the antigenic determinants. The results suggested that
      recognition of peptide E2-4 by T-cell clones was associated with HLA DR7.

PMID- 1383572
TI  - The role of urodynamic investigation in the assessment of benign prostatic
      hypertrophy.

PMID- 1383573
TI  - Use of the ASI titanium stent in the management of bladder outflow obstruction
      due to benign prostatic hyperplasia.
AB  - An expandable titanium intraprostatic stent was inserted into 30 patients with
      infravesical obstruction due to benign prostatic hyperplasia (BPH). All of the
      men were considered unsuitable for transurethral resection of the prostate as a
      result of comorbid conditions. In 25 patients effective micturition was
      reestablished with this technique. In 21 of these men, who have been followed for
      longer than 1 year, the mean maximum flow rate at 1 year was 10.8 ml. per second
      and the mean residual urine was 56 ml. Although urinary tract infections occurred
      subsequent to stent insertion in 10 individuals, these resolved after appropriate
      antibiotic treatment and no stents have had to be removed for this reason.
      Followup cystoscopy or examination by electron microscopy of those stents that
      have been removed has shown partial epithelialization of the stent surface in a
      proportion of patients, and a minor degree of incrustation occurred in 1 case. We
      conclude that an expandable intraprostatic titanium stent is an acceptable
      alternative to transurethral resection of the prostate or long-term
      catheterization in this particular group of high risk patients.

PMID- 1383571
TI  - In vitro enzymatic activity of human immunodeficiency virus type 1 reverse
      transcriptase mutants in the highly conserved YMDD amino acid motif correlates
      with the infectious potential of the proviral genome.
AB  - Reverse transcriptases contain a highly conserved YXDD amino acid motif believed
      to be important in enzyme function. The second amino acid is not strictly
      conserved, with a methionine, valine or alanine occupying the second position in
      reverse transcriptases from various retroviruses and retroelements. Recently, a
      3.5-A (0.35-nm) resolution electron density map of human immunodeficiency virus
      type 1 (HIV-1) reverse transcriptase positioned the YMDD motif within an
      antiparallel beta-hairpin structure which forms a portion of its catalytic site.
      To further explore the role of methionine of the conserved YMDD motif in HIV-1
      reverse transcriptase function, we have substituted methionine with a valine,
      alanine, serine, glycine, or proline, reflecting in some cases sequence motifs of
      other related reverse transcriptases. Wild-type and mutant enzymes were expressed
      in Escherichia coli, partially purified by phosphocellulose chromatography, and
      assayed for the capacity to polymerize TTP by using a homopolymeric template
      [poly(rA)] with either a DNA [oligo(dT)] or an RNA [oligo(U)] primer. With a
      poly(rA).oligo(dT) template-primer, reverse transcriptases with the methionine
      replaced by valine (YVDD), serine (YSDD), or alanine (YADD) were 70 to 100% as
      active as the wild type, while those with the glycine substitution (YGDD) were
      approximately 5 to 10% as active. A proline substitution (YPDD) completely
      inactivated the enzyme. With a poly(rA).oligo(U) template-primer, only the
      activity of mutants with YVDD was similar to that of the wild type, while mutants
      with YADD and YSDD were approximately 5 to 10% as active as the wild-type enzyme.
      The reverse transcriptases with the YGDD and YPDD mutations demonstrated no
      activity above background. Proviruses containing the reverse transcriptase with
      the valine mutation (YVDD) produced viruses with infectivities similar to that of
      the wild type, as determined by measurement of p24 antigen in culture
      supernatants and visual inspection of syncytium formation. In contrast,
      proviruses with reverse transcriptases containing the YADD and YSDD mutations
      were less infectious than wild-type virus. These results point to the critical
      role of methionine of the YMDD motif in the activity of HIV-1 reverse
      transcriptase and subsequent replication potential of the virus.

PMID- 1383575
TI  - Impact of radical prostatectomy on the characteristics of bladder and urethra.
AB  - A prospective study was done to evaluate the long-term effects of radical
      prostatectomy on the function of the bladder in filling and voiding. Preoperative
      urodynamic studies were done on 29 patients with a mean age of 62.9 +/- 5.2
      years. The preoperative results show that 16 of the 29 patients demonstrated
      detrusor instability with maximum contractile pressures of 59 +/- 28 cm. water.
      Followup urodynamic assessment was done in 13 of these patients 22.9 +/- 1.1
      months after surgery. Postoperatively, the maximum detrusor instability pressure
      did not decrease significantly (49 +/- 17 cm. water). Comparison of the operative
      and postoperative urodynamic characteristics of bladder filling shows that
      radical prostatectomy produced no significant change in the filling
      characteristics of the bladder in terms of bladder capacity, or volume at which
      sensations of fullness or urgency are reported. Voiding pressure-flow studies
      show a significant increase in maximum flow rate (8 +/- 1 to 13 +/- 2 ml., per
      second, p = 0.007), and significant decreases in maximum detrusor pressure (61 +/
      5.4 to 39 +/- 4 cm. water, p = 0.002), urethral opening pressure (45 +/- 7 to 25
      +/- 4 cm. water, p = 0.004) and residual volume (150 +/- 37 to 62 +/- 43 ml., p =
      0.019). Urethral profile measurements show that there was no significant change
      in either the maximum urethral closure pressure (94 +/- 9 to 83 +/- 9 cm. water)
      or external sphincter length (3.6 +/- 0.8 to 3.2 +/- 0.8 cm.). Preoperatively,
      the bladder neck pressures were 25 +/- 4.4 cm. water and were abolished after
      prostatectomy, indicating that the decrease in obstructive characteristics is due
      to removal of the prostate.

PMID- 1383574
TI  - Multicenter, randomized, double-blind, placebo controlled study to investigate
      the effect of finasteride (MK-906) on stage D prostate cancer.
AB  - A total of 28 untreated patients with asymptomatic, stage D prostate cancer was
      randomized in a double-blinded fashion to receive finasteride (10 mg. per day), a
      5 alpha-reductase inhibitor or placebo. Patients were evaluated at 3-week
      intervals by rectal examination, and serum prostate specific antigen (PSA) and
      prostatic acid phosphatase (PAP) levels, and at 6-week intervals by bone scan and
      transrectal ultrasound determinations of prostatic volume. Patients stopped the
      medication at week 6 at the discretion of the investigator when PSA levels
      increased from baseline. After 12 weeks all patients were reevaluated. Of the
      patients 13 received finasteride and 15 received placebo. The 2 groups did not
      differ statistically with respect to patient age, initial PSA and PAP level, or
      the extent of metastases on initial bone scan. A statistically significant
      decrease in the median percentage change from baseline in PSA at weeks 3 and 6
      occurred in the finasteride group compared to the placebo group (-22.9% versus 
      2.9% and -15.1% versus +11.7%, respectively, p less than 0.05). Finasteride had
      no effect upon PAP, serum testosterone, prostatic volume or appearance of bone
      scans. A decrease in serum PSA in the finasteride treatment group suggests that
      finasteride exerts a minor effect in patients with prostate cancer. This effect
      does not approach that seen with medical or surgical castration yet because of
      the potency preserving feature and the lack of toxicity finasteride may warrant
      further study in the treatment of prostate cancer.

PMID- 1383576
TI  - Lewis blood group antigen expression by cultured normal ureteral epithelial
      cells.
AB  - The importance of Lewis blood group antigens in recurrent urinary tract
      infections has led to a more detailed study of the expression of these antigens
      in an in vitro culture system. Expression of A, B, H, and Lewis blood group
      antigens by primary cultures of ureter epithelial cells was analyzed by flow
      cytometry. Cells maintained blood group determinants for up to 7 weeks in culture
      over three passages. In several specimens, the cells that exhibited expression of
      Lewis A (Le(a) and Lewis B (Le(b)) antigens increased dramatically over 2-3
      passages in culture. Lewis Y (Le(y)) antigen expression was positive on all
      primary cultures tested. The effect of fetal bovine serum (FBS) on blood group
      antigen expression was evaluated. Increased concentrations of FBS in the growth
      media increased the expression of Le(a) and Le(b) antigens in certain specimens,
      but did not affect expression of the other blood group antigens. The effect of
      FBS on blood group antigen expression of cultured cells depended on the Lewis
      blood type of the individual donating the specimen. To evaluate the heterogeneity
      often seen in Le(a) and Le(b) antigen expression, dual staining of cells for
      Le(a) and Le(b) antigens was performed. The results of these studies show for the
      first time that Lewis blood group antigens are expressed by cultured normal
      ureteral epithelial cells and that the pattern of expression of Le(a) and Le(b)
      changes over time. Furthermore, an individual cell may simultaneously express
      more than one Lewis antigen on its surface.

PMID- 1383577
TI  - Relief from pain and the double effect.

PMID- 1383579
TI  - A case of vasovagal syncope with convulsions--the effects of midodrine
      hydrochloride.
AB  - A 42-year-old female had suffered from repeated syncope. She had vasovagal
      syncope with convulsions from vasodilatation and cardiac standstill which lasted
      for 9.8 sec. The 60 degrees head-up tilt test, nitroglycerin injection and
      isoproterenol infusion provoked vasovagal reaction. Although a beta blocker was
      not effective in preventing tilt-induced hypotension and bradycardia, midodrine
      hydrochloride (alpha-1 stimulant) or atropine prevented it. In this patient,
      insufficient constriction of capacitance vessels might have played an important
      role in activation of an inhibitory reflex from cardiopulmonary mechanoreceptors
      which caused hypotension and bradycardia.

PMID- 1383578
TI  - Beta-3 adrenergic agonist, BRL-26830A, and alpha/beta blocker, arotinolol,
      markedly increase regional blood flow in the brown adipose tissue in anesthetized
      rats.
AB  - Regional vascular effects of some adrenergic agents, focussing on brown adipose
      tissue (BAT), were investigated using tracer microspheres with a reference sample
      method in the anesthetized rat. Intravenous injections of 0.5 mg/kg BRL-26830A, a
      beta 3-adrenergic agonist, increased heart rate, but changes in blood pressure
      and cardiac output were not significant. The drug decreased blood flow in the
      brain, the spleen and the kidneys, but markedly increased it in BAT. At 2 mg/kg,
      arotinolol, an alpha/beta-adrenergic blocker, decreased blood pressure by 20 mmHg
      and increased cardiac output by 95 ml/min/kg. It slightly but significantly
      decreased blood flow in the liver and the spleen, but markedly increased the flow
      in BAT. Acebutolol, a beta 1-adrenergic blocker, decreased blood flow in the
      liver, the spleen, the pancreas, the kidneys, the adrenals, the skeletal muscle
      and the skin. Bunazosin, an alpha 1-adrenergic blocker, decreased it in all
      organs and tissue expect the brain and BAT. The pattern of redistribution of
      blood flow by arotinolol was very similar to that caused by BRL-26830A.
      Acebutolol and bunazosin rather decreased the blood flow in the BAT. These
      results indicate that stimulation of beta 3-adrenergic receptors, in BAT results
      in vasodilation, and that arotinolol may bind to those beta 3-adrenergic
      receptors.

PMID- 1383580
TI  - [CD7 (+) stem cell leukemia presenting different phenotypes in lymph node and
      bone marrow].
AB  - A 27-year-old male with systemic lymphadenopathy was diagnosed as lymphoblastic
      type lymphoma by inguinal lymph node biopsy in September, 1990. Bone marrow at
      the initial diagnosis contained 55.4% lymphoblasts with a phenotype of peroxidase
      (-), CD7 (+), CD4 (-), CD8 (-). Lymphadenopathy and lymphoblasts in bone marrow
      disappeared after MACOP-B therapy. In December, 1990, however, the patient again
      noticed swelling of cervical lymph nodes. At this time, the bone marrow contained
      36.4% myeloblasts with a peroxidase (+), CD7 (+), CD13 (+), CD33 (+) phenotype.
      Cytogenetic and genetic study revealed that the lymphoblasts at the initial
      diagnosis and the myeloblasts at relapse shared an common abnormal karyotype, 11p
      , and the same rearranged band of T-cell receptor delta, gamma, beta genes,
      suggesting that these two blasts originated from the same clone. The blasts
      obtained from the cervical lymph node at relapse were still negative for
      peroxidase, in contrast to the blasts from bone marrow. These findings suggest
      that this leukemia originated from a stem cell and differentiated along
      multilineage pathways.

PMID- 1383581
TI  - [Sample preparation for PCR from pathological specimens].

PMID- 1383582
TI  - [Two cases of alpha-fetoprotein producing early gastric cancers].

PMID- 1383583
TI  - Immunohistochemical classification of astrocytes in infants by glial fibrillary
      acidic protein staining and application to forensic practice.
AB  - This study was designed to assess whether development of the astrocytes in
      central nervous system (CNS) is delayed in victims of the sudden infant death
      syndrome (SIDS), and to try the classification of astrocytes by a morphological
      method. The glial fibrillary acidic protein (GFAP) is the major component of
      astrocytic fiber and is characteristic of astrocytes in the human CNS. An
      immunohistochemical study identificating this protein was carried out on infant
      brains to evaluate astrocytes. Morphologically 39 brains of infants aging under
      12 months old, that including 10 asphyxia, 13 respiratory infections and 16 SIDS
      cases, were stained for GFAP by the peroxidase-anti-peroxidase (PAP) method.
      According to their staining pattern astrocytes were classified into 4 cell types:
      Type I cells were seen during the non-proliferating period, Type II cells during
      the low-proliferating period, Type III cells during the moderate-proliferating
      period and Type IV cells during the high-proliferating period. On the basis of
      this classification of astrocytes, it was observed that the first and most
      reactive pattern of physiological proliferation was in infant brains four months
      old after birth in the asphyxia cases. The staining grade of astrocytes was
      significantly less in white matter in the SIDS victims compared with age-matched
      of the respiratory infections and asphyxia. Therefore, we suggest that
      development of brain in the SIDS cases is delayed to controls and that the SIDS
      is associated with a developmental CNS disorder. Among 3 group cases the retarded
      staining pattern of the astrocytes in SIDS is interesting and might give a
      helpful approach to diagnosis of the cause of death for SIDS.

PMID- 1383584
TI  - Effects of adrenergic agonists on an experimental urinary incontinence model in
      anesthetized rabbits.
AB  - We have developed an experimental urinary incontinence model in anesthetized
      female rabbits, in order to study the effects of alpha-adrenergic receptor
      agonists on it in vivo. Micturition was induced artificially by electrical
      stimulation of the abdomen of rabbits receiving a continuous infusion of glucose
      free. Tyrode's solution into the urinary bladder. Alpha-1 adrenergic agonists,
      phenylephrine (1 mg/kg, i.v.) and the newly synthesized agent ST-1059 (1 mg/kg,
      i.v.) and its prodrug midodrine (10 mg/kg), which was intraduodenally
      administered, elevated the bladder pressure and arrested micturition induced by
      electrical stimulation. Prazosin (0.1 mg/kg, i.v.) inhibited these effects of
      phenylephrine. The effect of an alpha-2 agonist, clonidine (1 mg/kg, i.v.), on
      micturition induced by electrical stimulation was not clearly defined. This study
      demonstrates that alpha-1 adrenergic agonists can arrest artificially-induced
      micturition via urethral contraction. This method may be useful for evaluating
      the effect of a drug on urethral leakage in vivo.

PMID- 1383586
TI  - [Pulmonary epithelial permeability in rats with bleomycin-induced pneumonitis].
AB  - This study was performed to investigate the mechanism by which 99mTc-DTPA
      molecules pass through the pulmonary epithelium following inhalation of 99mTc
      DTPA aerosol. Interstitial pneumonitis was induced in 6-week-old male rats by
      instilling 1 mg/kg of bleomycin into the trachea. Disappearance of radioactivity
      from the lungs was measured with a gamma camera every 2 weeks to estimate
      pulmonary epithelial permeability, and light- and electron-microscopic
      histopathologic examinations were performed at the same intervals. There was a
      statistically significant increase in the pulmonary epithelial permeability at 2
      weeks after the instillation of bleomycin. However, subsequent changes in
      pulmonary epithelial permeability were not uniform; some animals showed recovery
      and some showed further increase and/or partial recovery. Microscopically,
      increase in the capillary bed, round cell infiltration, and widening of the
      interstitial space were observed in addition to the presence of macrophages in
      the alveolar spaces at 2 weeks. Electron microscopic examination revealed
      vacuolization, thinning and detachment of the alveolar epithelium, and denudation
      of the basement membrane. Prominent fibrosis, honeycombing, thinning of the
      pulmonary epithelium, and increase in collagen fibers were observed after 18
      weeks. We consider that vacuolization, thinning, and detachment of the pulmonary
      epithelium and denudation of the basement membrane are related to the increase in
      pulmonary epithelial permeability in bleomycin-induced interstitial pneumonitis.

PMID- 1383585
TI  - [Nosocomial respiratory infection caused by Pseudomonas cepacia in
      immunocompromised hosts].
AB  - Pseudomonas cepacia is a gram negative rod, having no fermentative activity on
      glucose. This organism was detected in the sputum, throat swab, or throat washing
      of 22 inpatients treated between January, 1990, and December, 1990, at the First
      Department of Internal Medicine, Kagawa Medical School. The primary diseases for
      which these 22 patients were hospitalized were leukemia in 12, malignant lymphoma
      in 5, lung cancer in 2, myelodysplastic syndrome in 1, and embryonal cell
      carcinoma in 1. Twelve of the 22 patients had episodes of pneumonia which
      complied clinically with the diagnostic criteria provided to facilitate the
      National Nosocomial Infection Study. The complication of pneumonia occurred in 7
      patients with leukemia, 2 with malignant lymphoma, 2 with lung cancer, and 1 with
      myelodysplastic syndrome. In 10 of these 12 patients, the organism was detected
      before the onset of pneumonia. All 22 patients in whom the organism was
      demonstrated had received antibiotics. The antibiotics which was most frequently
      used to treat these patients 1 month before detection of Pseudomonas cepacia were
      amikacin and ceftizoxime, which were used in 13 patients. Of the antibiotics in
      which the susceptibility to Pseudomonas cepacia was, evaluated, minocycline was
      effective in 100% (21/21), ceftazidime in 50% (11/22), and ofloxacin in 27.3%
      (6/22). Physicians should be especially aware of the possibility of colonization
      and nosocomial respiratory infection by Pseudomonas cepacia in patients with
      severe underlying diseases.

PMID- 1383587
TI  - [A case of large cell carcinoma of the lung which is suspected of producing
      granulocyte colony-stimulating factor].
AB  - A 41-year-old male complaining of fever and left shoulder pain was admitted to
      our hospital for further examination of an abnormal shadow on chest X-ray film.
      His laboratory data on admission showed marked leukocytosis and elevation of
      serum alkaline phosphatase. The diagnosis of large cell carcinoma of the lung was
      made by percutaneous biopsy and he was staged clinically as T3N0M0. Chemotherapy
      including CDDP and VDS resulted in resolution of symptoms and normal laboratory
      data. After three courses of chemotherapy, he underwent left upper lobectomy with
      chest wall resection. Pathological diagnosis of the resected tumor was large cell
      carcinoma with giant cells, and he was staged postoperatively as T3N0M0. Since
      colony stimulating activity was demonstrated in both homogenate of tumor cells
      and tumor conditioned medium, and preoperative serum granulocyte colony
      stimulating factor (G-CSF) was 105 pg/ml, we concluded that leukocytosis in this
      patient was caused by G-CSF produced by tumor cells. The patient was in good
      health two years after surgery with no signs of recurrence.

PMID- 1383588
TI  - [A case of aortic valve stenosis and regurgitation with idiopathic
      thrombocytopenic purpura].
AB  - A patient of aortic valvular disease with idiopathic thrombocytopenic purpura
      underwent aortic valvular replacement. We report a preventive measure against the
      intra and postoperative bleeding. The patient was a 67-year-old man. He was
      diagnosed as aortic valvular stenosis with regurgitation. There was no abnormal
      data about the coagulation test. Thrombocyte count was 8.2 x 10(4)/mm3, but
      thrombocytopenic life span had shortened 3.8 days. So, we used gamma-globulin 400
      mg/kg/day for 5 days before the day of operation and infused blood platelets on
      the day of operation. There was no problem intra and postoperative period. On the
      14th postoperative day thrombocyte count increased to 22.9 x 10(4)/mm3, and
      thrombocytopenic life span returned to normal range (7.6 days). But on the 45th
      day of postoperation, thrombocyte count decreased to 11.0 x 10(4)/mm3. We think
      that many gamma-globulin medication is a useful method to prevent intra and
      postoperative bleeding resulting from idiopathic thrombocytopenic purpura.

PMID- 1383589
TI  - [Intraoperative blood recovery in transurethral resection of prostate (TURP)].
AB  - Blood collected from irrigating fluid in TURP was studied if it was appropriate
      blood as autologous transfusion or not. TURP was performed aided by continuous
      irrigation through suprapubic cystostomy. The cystostomy tube was connected to
      the Shiley STAT or Haemonetics Cell Saver in 15 patients. The average weight of
      resected adenoma was 36 g per patient. The product of washed blood gave an
      average yield of 440 ml per patient with an average RBC count of 469 x 10(3)/mm3,
      hemoglobin of 14.6 g/dl, hematocrit of 44.8%, platelets of 15400/mm3. The half
      life of collected red blood cells tagged with 55Cr was 22 days. The urine in 10
      patients (67%) were contaminated with bacteria before TURP, and 3 of collected
      blood were contaminated with bacteria (20%). As for carcinoma cells, cultured
      urinary bladder carcinoma cells (T24) and renal carcinoma cells (ACHN) were
      completely eliminated after filtration through leukocyte removal filter Sepacell
      or Pall RC. As results, the intraoperatively collected blood from irrigating
      fluid in TURP was useful and safe as autologous blood transfusion.

PMID- 1383591
TI  - [Clinico-immunological aspects of idiopathic ventricular arrhythmia].
AB  - The clinicoimmunological study revealed immunocompetence dysfunction in 28
      patients with idiopathic ventricular arrhythmias resistant to ritmilen. After
      sodium nucleinate immunomodulation, ritmilen therapy proved to be beneficial in
      46.6% of the patients. A positive result was obtained only in the patients who
      showed the same or close values as in healthy individuals. The comparison has led
      to the conclusion that idiopathic ventricular arrhythmias are directly related to
      immune dysfunction and to the recommendation that sodium nucleinate should be
      used in the multimodality therapy of the arrhythmias.

PMID- 1383590
TI  - [Use of an anti-arrhythmia drug mexicord in the treatment of ventricular
      extrasystole].
AB  - The antiarrhythmic agent mexicord (Polfa, Poland) versus ethmozine underwent a
      clinical trial. Meticord was found to have a marked antiarrhythmic effect and be
      useful in the long-term management of patients with ventricular tachyarrhythmias.

PMID- 1383592
TI  - [Use of rheogluman in the acute period of myocardial infarction].
AB  - The efficacy of rheogluman was evaluated in 55 patients with acute myocardial
      infarction. ECG mapping recordings in 35 leads showed that an earlier positive
      dynamics in sigma ST, sigma Q, and sigma R was significantly observed in patients
      treated with rheogluman than in untreated patients. These data indirectly
      indicated a reduction in the ++peri-infarct zone in the acute period of
      myocardial infarction. The serum concentrations of lysosomal enzymes (creatine
      phosphokinase, lactate dehydrogenase, aspartate aminotransferase, alanine amino
      transferase) became normal earlier in the rheogluman-treated patients than in the
      controls. This fact may be regarded as a protective effect of the drug on the
      formation of a necrotic focus.

PMID- 1383594
TI  - [Anti-arrhythmic effectiveness of neogilurhythmal in extrasystolic arrhythmia].
AB  - The paper provides the results of differential neogilurythmal therapy in 20
      patients with high-grade atrial and ventricular premature contractions in the
      presence of coronary heart disease. The detection of cardiac arrhythmias and
      evaluation of the antiarrhythmic efficacy of neogilurythmal were performed by
      Holter monitoring and transesophageal electrophysiological study. After the
      baseline studies, the antiarrhythmic efficacy of the drug was evaluated during an
      acute drug test and then during a 8-day course of the therapy. In the acute drug
      test, the dose of neogilurythmal was 50% of the daily dosage. The studies
      indicated that neogilurythmal in a dose of 80 mg/day was beneficial in affecting
      both the atrial and ventricular extrasystolic arrhythmia. The agent failed to
      alter heart rate, sinus nodal function and atrioventricular conduction. Thus,
      neogilurythmal is low toxic and produces no adverse effects when given in the
      definite dosage range.

PMID- 1383593
TI  - [Effects of digoxin on ventricular arrhythmia in patients with heart failure:
      relations with the state of the sympathetic-adrenal system].
AB  - Ventricular arrhythmias were analysed in 38 patients with Stages I-IIB heart
      failure from 24-hour Holter monitoring data obtained before and after digoxin
      therapy by comparing with the concentrations of catecholamines. There was a
      direct relationship between the plasma levels of epinephrine and norepinephrine
      and the severity of ventricular arrhythmias, as well as between the changes in
      cumulative catecholamine levels and ventricular arrhythmias during digoxin
      therapy. Virtually in all cases, the antiarrhythmic effect of the drug was
      accompanied by lower plasma catecholamine concentrations whereas the levels of
      norepinephrine and epinephrine remained nearly unchanged or increased with the
      tentatively arrhythmogenic action. The findings may suggest that
      hypercatecholaminemias are essential in the genesis of ventricular arrhythmias in
      heart failure. Cardiac glycosides can heterogeneously affect ventricular
      arrhythmias by modifying the activity of the sympathoadrenal system.

PMID- 1383595
TI  - EDRF modulates renal hemodynamics during unilateral ureteral obstruction in the
      rat.
AB  - Unilateral ureteral obstruction (UUO) results in vasoconstriction of the
      ipsilateral kidney, and vasodilatation of the intact opposite kidney. To
      investigate the role of endogenous nitric oxide, an endothelial-derived relaxing
      factor (EDRF), in the regulation of renal hemodynamics during UUO, Sprague-Dawley
      rats were anesthetized for study 24 hours after left UUO or sham-operation. Total
      vascular resistance (TVR) and renal vascular resistance (RVR) were measured using
      radioactive microspheres during control periods and following infusion of the
      nitric oxide synthase inhibitor, L-NAME (2.5 mg/kg). Blood pressure and RVR were
      increased by L-NAME, with a greater increment in the RVR/TVR ratio of the kidney
      with ipsilateral UUO than in the intact opposite kidney or sham-operated kidneys.
      Infusion of L-arginine (L-Arg), a substrate for nitric oxide synthase, did not
      alter the RVR/TVR ratio of either kidney of rats with UUO, but reduced the ratio
      in sham-operated animals. L-NAME tended to reduce urine flow and urinary sodium
      and cyclic GMP excretion, whereas L-Arg resulted in a marked diuresis,
      natriuresis, and increased excretion of cyclic GMP in both operative groups. We
      conclude that EDRF activity is increased in the kidney with ipsilateral UUO,
      which serves to counteract renal vasoconstriction. This response is not limited
      by availability of substrate (L-Arg). Vasodilatation of the intact opposite
      kidney appears to be mediated by factors other than EDRF.

PMID- 1383597
TI  - A cell-type specific ganglioside of glomerular podocytes in rat kidney: an O
      acetylated GD3.
AB  - We recently described a monoclonal antibody (clone 27A) that detected a membrane
      antigen specific for glomerular podocytes in adult rat kidney. After binding in
      vivo, the antibodies induced rapid changes in the foot processes. Here we show
      that in other rat tissues the antigen is detectable only in cells of adrenal
      medulla, in some cells of neural or neural crest origin, and in 1 to 5% of the
      cells of a rat pheochromocytoma cell line PC-12. Attempts to isolate the antigen
      revealed that it is an acidic, sialic acid containing lipid, as shown by thin
      layer chromatography and immuno-overlay techniques. Further characterization of
      the gangliosides extracted from rat glomeruli, bovine kidney, rat adrenal glands,
      or from PC-12 cells by ion exchange, thin layer, and gas liquid chromatography
      identified the antigenic lipid as a modified disialosyllactosylceramide (GD3).
      The results of mild alkaline treatment or periodate oxidation of the antigenic
      ganglioside, as well as chemical O-acetylation studies of standard gangliosides,
      showed that the modified ganglioside is O-acetylated, most probably at the 9
      carbon of its terminal sialic acid residue. To our knowledge this is the first
      report of cell-type specific expression of gangliosides in the kidney.

PMID- 1383596
TI  - Altered glomerular extracellular matrix synthesis in experimental membranous
      nephropathy.
AB  - Chronic progressive membranous nephropathy (MN) in humans is characterized by
      thickening of the glomerular basement membrane (GBM) with formation of spikes
      which contain laminin and other extracellular matrix (ECM) proteins. We have
      utilized two models of MN in the rat (active and passive Heymann nephritis, AICN,
      PHN) to define the sequential changes in composition of GBM as they relate to
      changes in glomerular gene expression for ECM components, altered permeability
      and morphological changes. Renal biopsies obtained during the course of AICN and
      PHN were immunostained for various ECM proteins and total glomerular RNA was
      hybridized with cDNA probes specific for laminin B2-chain, s-laminin, and types I
      and IV collagen. In addition, the ability of anti-glomerular epithelial cell
      (GEC) antibody and complement on rat GEC in culture to induce laminin release or
      laminin and s-laminin mRNA expression was determined. The results demonstrate
      that at weeks 12, 16, and 20 of AICN, immunostaining for laminin, s-laminin,
      fibronectin, entactin, and heparan sulfate proteoglycan increased in the GBM in a
      spike-like pattern. Concomitantly, glomerular mRNA levels of laminin B2-chain and
      of s-laminin increased. Type IV collagen protein and gene expression remained
      unchanged or decreased. No glomerular immunostaining for type I collagen occurred
      during AICN despite increased expression of mRNA for this collagen type. In
      contrast to AICN, in PHN no pronounced changes of the glomerular ECM occurred,
      except for transient expression of type I collagen mRNA in whole glomerular RNA
      and type I collagen protein the GEC cytoplasm. Stimulation of GEC in culture with
      anti-GEC antibody and complement also failed to induce transcription of laminin
      or s-laminin mRNA or the release of laminin protein. These findings suggest that
      the polyantigenic expansion of GBM which occurs in chronic experimental MN may be
      stimulated by factors different from the C5b-9 mediated processes that cause the
      initial proteinuria.

PMID- 1383598
TI  - Expression of insulin-like growth factor binding protein-1 mRNA in human fetal
      kidney.
AB  - Expression of insulin-like growth factor binding protein-1 (IGFBP-1) messenger
      RNA (mRNA) was studied in tissues of human fetuses from 15 to 23 weeks of
      gestation. Northern blot analysis revealed IGFBP-1 mRNA in the fetal liver and
      kidney but not in other fetal tissues, including the brain, heart, lung, skeletal
      muscle and spleen. Studies by in situ hybridization histochemistry showed that,
      in all fetal kidneys tested, the IGFBP-1 mRNA was localized preferentially to the
      epithelial cells of the collecting ducts, as well as to the cells of developing
      glomeruli and in the subcapsular nephrogenic mesenchyme. Less intense labeling
      for IGFBP-1 mRNA was seen in the connective tissue stroma of the medullary
      pyramids. A weak signal was detected in the mature glomeruli, and in the cells of
      the medullary mesenchyme and capsular connective tissue. IGFBP-1 protein was
      detected by immunoperoxidase staining mostly around small blood vessels but not
      in the respective endothelium. The protein was also present in many epithelial
      cells of the collecting ducts and in stromal connective tissue. These results
      show that the predominant sites of IGFBP-1 transcription in the developing kidney
      are those with most active differentiation.

PMID- 1383599
TI  - Molecular immunology and immunopharmacology of allograft rejection.

PMID- 1383600
TI  - [Adjustment disorders with developmental risk in children after inpatient
      treatment].
AB  - The relatively broad spectrum of symptoms in child psychiatry (disturbances of
      behaviour and of anxiety and others) was examined in order to find smaller
      diagnostic groups. Two selected groups of probands of the Department of Child and
      Adolescent Psychiatry at the University Hospital for Children in Jena were
      analysed. This analysis was made by recording journals of treatment and a
      questionnaire. Both groups differed significantly in 33 out of 128
      characteristics. The following factor analysis resulted in 10 anxiety- and non
      anxiety-syndromes leading back to basic disturbances of affect, psychomotoricity
      and thinking as well as to exogenous variables like social surroundings and
      conditions in varieties in upbringing and education. A proof and reliable
      classification is not possible because of individually and qualitatively
      different symptoms. The results of the study show the necessity of an effective
      and improved dispensary care.

PMID- 1383601
TI  - [Differences in detectability of human immunodeficiency virus type 1 in tears and
      blood lymphocytes].
AB  - Reported data on the isolation of the human immunodeficiency virus type 1 (HIV-1)
      from tears are controversial. The purpose of the study was to try to isolate HIV
      1 from tears in a large sample of HIV-1-positive patients at different stages of
      infection. 53 tear samples were obtained from 50 patients. Additionally isolation
      of HIV-1 from peripheral blood lymphocytes (PBL) was attempted. HIV-1 was
      isolated from none (= 0%) of the 53 tear samples. Isolation from PBL was
      successful depending on absolute CD4+ lymphocyte count and Walter Reed staging
      (Walter Reed stage 6: 83%; stage 2 to 5: 11%; p less than 0.0001). Treatment with
      zidovudine was not related to the frequency of HIV-1 isolation. These results
      suggest that tears of patients infected with HIV-1 contain low or no quantities
      of tissue-culture-infectious units of HIV-1. Nosocomial infection with HIV-1 from
      tears appears to be unlikely. The known precautions for the prevention of spread
      of viral disease in ophthalmological practice are sufficient and should be
      strictly followed.

PMID- 1383602
TI  - [Microscopic examination of conjunctival specimens from patients with cicatricial
      pemphigoid].
AB  - The conjunctiva's materials from patients with cicatricial pemphigoid were
      examined histopathologically and ultrastructurally. Non specific changes were
      shown at the cellular level: leukocytes infiltrations and increase in the amount
      of connective tissue which cause the scars. Ultrastructurally increase in the
      number of collagen fibres and disorders in the structure of basal membrane of
      epithelium were shown. Pathological changes were located mostly in lamina propria
      of tunica mucosae.

PMID- 1383603
TI  - Mitochondrial abnormalities in the DIDMOAD syndrome.

PMID- 1383604
TI  - Fatal cytochrome c oxidase-deficient myopathy of infancy associated with mtDNA
      depletion. Differential involvement of skeletal muscle and cultured fibroblasts.

PMID- 1383605
TI  - 3-Methylglutaconyl-coenzyme-A hydratase deficiency: a new case.

PMID- 1383606
TI  - Tryptophan therapy for non-ketotic hyperglycinaemia.

PMID- 1383607
TI  - Angiogenesis and tumor progression of melanoma. Quantification of vascularity in
      melanocytic nevi and cutaneous malignant melanoma.
AB  - BACKGROUND: The capacity of cutaneous malignant melanoma (CMM) to induce
      angiogenesis is well established. In addition, dysplastic melanocytic nevi (DMN)
      have been reported to display prominent vascularity relative to common acquired
      nevi; but this observation has never been verified objectively. EXPERIMENTAL
      DESIGN: In the following studies, papillary dermal or tumor vascularity was
      quantified in 10 examples of normal skin, and in a series of 18 melanocytic nevi,
      29 DMN, 37 primary CMM and 5 melanoma metastases. Microvessels were identified
      with the lectin Ulex europaeus agglutinin I. The number of microvessels were
      counted with an ocular grid (area 7.84 x 10(-2) mm2) at x400 magnification, and
      the mean vascularity recorded for five fields for each specimen. RESULTS: Mean
      vascular counts were as follows: normal skin 5.9, common acquired nevus 9.1,
      nevus with features of DMN 10.3, DMN, slight atypia 11.8; DMN, moderate atypia
      12.2; DMN, severe atypia 14.8; primary CMM 25.4; and metastatic melanoma 29.5).
      Significant differences were recorded for DMN, severe atypia versus melanoma (p
      less than 0.01), DMN, severe versus common nevi (p less than 0.02) and versus
      nevi with features of DMN (P less than 0.05). When microvessel counts from CMM in
      the radial growth phase were compared with those from CMM in the vertical growth
      phase, or CMM less than 1.0 mm versus those greater than 1.0 mm, no significant
      differences were found. However, CMM in radial growth did differ from severely
      atypical DMN (22.4 versus 14.8, p less than 0.05). CONCLUSIONS: These results
      quantify for the first time a gradual rise in vascularity with tumor progression
      in the melanocytic system and onset of angiogenesis during the radial growth
      phase of CMM. Other than severely atypical DMN, DMN did not differ substantially
      from common nevi with reference to overall vascularity.

PMID- 1383608
TI  - Morpheme learning of children with specific language impairment under controlled
      instructional conditions.
AB  - Three groups of children were exposed to instances of a novel morpheme under
      controlled experimental conditions. The performance of 32 children with specific
      language impairment (SLI), aged 5:0 to 7:0 years (years:months), was compared to
      that of 24 normally developing children matched for age and nonverbal ability and
      20 younger normally developing children matched for language development and
      nonverbal ability. The children were taught under two instructional conditions
      that differed only in whether the child was asked to imitate the new language
      form after each instance (imitation) or just to observe its use (modeling).
      Consistent with past research (Connell, 1987b), the children with SLI performed
      significantly better under the imitation condition than under modeling, but the
      age-matched controls showed no difference in response to instruction. The
      performance of the language-matched controls was similar to that of the age
      matched controls, suggesting that the instruction-specific effect for the
      children with SLI is not merely a function of general language immaturity.
      Although the superiority of the imitation condition for the children with SLI was
      evident for test trials requiring production of the new morpheme (as in past
      research), no such effect was evident for comprehension trials. This differing
      effect of output demands suggests that the SLI-specific response to instruction
      is not a matter of different mastery of the new rule but rather is specific to
      the need to access the newly induced rule on production trials. The accessing of
      phonological representations as a possible explanation for the effect is
      discussed.

PMID- 1383609
TI  - Cholecystokinin upregulation during intestinal repair.
AB  - To determine whether cholecystokinin (CCK), a small intestinal hormone, may have
      autocrine or paracrine functions, gene regulation in the rat stomach and duodenum
      has been evaluated following cytotoxic injury. We quantified total RNA, CCK
      messenger RNA (mRNA), total protein, small and large forms of CCK peptides and
      gastrin. The stomach and the intestine respond differently. Following cytotoxic
      injury duodenal total RNA falls (1.5 +/- 0.1 vs 0.18 +/- 0.04 mg/g P less than or
      equal to 0.0001), and CCK mRNA content is depleted (260 +/- 23 vs 41 +/- 8 pg CCK
      mRNA/duodenum P less than or equal to 0.0001), yet there is a paradoxical
      increase in CCK mRNA concentration (176 +/- 20 vs 303 +/- 38 pg CCK mRNA/mg total
      RNA P less than or equal to 0.01). Increases occurred in both molecular species
      of CCK peptides evaluated: CCK8 (8 +/- 7 vs 26 +/- 2 pmole/g P less than or equal
      to 0.0001), large forms of CCK (42 +/- 4 vs 250 +/- 27 pmole/g P less than or
      equal to 0.0001). By contrast, in the stomach, only decreases were observed.
      These data identify sites of anatomical and biosynthetic upregulation during
      gastrointestinal repair. Changes are dependent upon the length of the period of
      recovery, differ between stomach and duodenum, and may be age related. Intestinal
      CCK may have para- and or autocrine roles in addition to its hormone function.

PMID- 1383610
TI  - Altered ryanodine receptor of canine cardiac sarcoplasmic reticulum and its
      underlying mechanism in endotoxin shock.
AB  - Effects of endotoxin administration on ryanodine receptor in canine cardiac
      junctional sarcoplasmic reticulum (SR) were studied. The results show that the
      Bmax for [3H]ryanodine binding to cardiac junctional SR was decreased by 25% (8
      +/- 0.38 vs 6 +/- 0.41 pmole/mg protein for control and endotoxic, respectively;
      (P less than 0.01) while the kd (13.7 +/- 1 nM for control vs 13.2 +/- 2 nM for
      endotoxic) was unaffected 4 hr following endotoxin administration. Ca2+ activated
      [3H]ryanodine binding in both groups sigmoidally but the Vmax for Ca2+ activation
      was decreased by 24% (P less than 0.05) while the S0.5 and the Hill coefficient
      values remained unchanged after endotoxin injection. Caffeine, ATP, and AMP-PCP
      activated while calmodulin, SKF-525A, ruthenium red, and Mg2+ inhibited
      [3H]ryanodine binding in both groups but the A0.5 (concentration requires for
      half-maximum activation) and the I50 (concentration requires for half-maximum
      inhibition) for the above-mentioned activators and inhibitors, respectively, were
      unaffected during endotoxin shock. Digestion of cardiac SR isolated from control
      dogs with phospholipase A2 inhibited [3H]ryanodine binding and the inhibition was
      reversed completely by the addition of phosphatidylserine. Addition of
      phosphatidylserine to cardiac SR isolated from endotoxic dogs stimulated
      [3H]ryanodine binding and the stimulation represents a complete reversal of the
      inhibition caused by endotoxin administration. Based on these findings together
      with previous observation that phospholipase A2 activity is activated during
      endotoxin shock, it is concluded that endotoxin administration decreases the
      number of ryanodine receptor in canine cardiac junctional SR and the decrease in
      ryanodine receptor is associated with a mechanism involving a modification of
      membrane lipid microenvironment in response to phospholipase A2 activation.

PMID- 1383611
TI  - A role for ELAM-1 in the pathogenesis of MOF during septic shock.
AB  - As a model for septic shock, LPS was infused into anesthetized Cynomolgus
      monkeys. Hematologic and metabolic parameters proved the induced shock response.
      The data presented show that administration of LPS to Cynomolgus monkeys induced
      a generalized inflammatory status, which was characterized by systemic release of
      the cytokines TNF and IL-6. Further it was demonstrated, using immune
      histological methods, that a generalized expression in vivo of the endothelial
      leukocyte adhesion molecule (ELAM)-1 was induced on endothelial cells by LPS
      infusion. ELAM-1 expression was most pronounced on vasculature of lung tissue and
      skin. As shown in serial skin biopsies, ELAM-1 expression was induced rapidly: at
      2 hr after the onset of LPS infusion, reaching maximum after 4 hr. The expression
      of ELAM-1 is considered to be of relevance for the mechanism which underlies the
      stasis of PMN in the tissues during septic shock.

PMID- 1383612
TI  - FK-506 inhibits proliferation and IL-4 messenger RNA production by a T-helper 2
      cell line.
AB  - FK-506 is a potent immunosuppressant which is known to decrease the generation of
      allospecific cytotoxic T cells, possibly through its effect on cytokine
      production. FK-506 has been reported to have a suppressive effect on cytokine
      synthesis and secretion by pooled lymphocytes; its action on more selective
      subsets of lymphocytes is unknown. We currently report the effect of FK-506 on
      proliferation and IL-4 messenger RNA production by the differentiated mouse T
      helper 2 cell line Ly1+2-/9. Ly1+2-/9 cells were grown in culture and treated
      with (1) media alone, (2) Con A, (3) FK-506, and (4) Con A + FK-506.
      Proliferation to Con A was determined by treating cells with 10 micrograms/ml Con
      A +/- FK-506 and measuring [3H]TdR uptake. Reverse transcriptase-polymerase chain
      reaction amplification was used to quantitate the level of IL-4 mRNA expression.
      FK-506 markedly inhibits Con A-induced proliferation and IL-4 mRNA production by
      the T-helper 2 cell line Ly1+2-/9. The ability of FK-506 to block the
      proliferation and IL-4 production by this helper cell subset suggests that this
      effect may contribute to its observed marked immunosuppressive properties in
      vitro and in vivo.

PMID- 1383613
TI  - Effect of cyclosporine on adrenocortical response to injury and infection.
AB  - The effects of cyclosporine administration on the adrenocortical response to the
      severe stress of burn wound sepsis were studied in Wistar rats. Animals were
      treated with cyclosporine (10 mg/kg/day) or saline by gavage for 10 days, then
      subjected to 30% scald burns with wound inoculation with Pseudomonas. Animals
      were sacrificed on Postburn Days (PBDs) 1, 4, and 7 for determination of serum
      corticosterone and ACTH levels and adrenal weights and histology. Adrenal glands
      from animals sacrificed on PBD 7 were also analyzed for DNA, RNA, and protein
      content. Cyclosporine treatment without injury had no significant effect on body
      weight gain, adrenal mass, or baseline ACTH or corticosterone levels. During
      sepsis, cyclosporine-treated animals demonstrated a significantly diminished
      adrenocortical response compared to those given only saline. Serum corticosterone
      levels in the cyclosporine group were 45, 53, and 62% lower on PBDs 1, 4, and 7,
      respectively, than in saline-treated controls (P < 0.01 on each day). ACTH levels
      were 43 and 36% lower in cyclosporine-treated animals on PBDs 4 and 7,
      respectively, compared to the saline-treated group (P < 0.05 on each day).
      Adrenal hyperplasia occurred in both groups by PBD 7, but increases in adrenal
      mass and in histologic changes associated with hyperplasia (lipid depletion,
      vascular dilation) were less pronounced in cyclosporine-treated animals compared
      to those receiving saline, while adrenal composition remained similar between the
      two groups. Thus, cyclosporine administration is associated with an attenuated
      adrenocortical response to the stress of sepsis due to diminished circulating
      levels of ACTH.

PMID- 1383614
TI  - The response of the rabbit rectus femoris muscle to ischemia and reperfusion.
AB  - The rectus femoris muscle of the rabbit is perfused by a single artery and vein
      and is a valuable new model for study of ischemia-reperfusion injury of skeletal
      muscle. The consequences of increasing duration of ischemia to the rectus femoris
      have been examined. Postischemic muscle survival (means +/- SEM), as measured by
      Nitro blue tetrazolium (NBT) staining 24 hr after ischemia, was 90.5 +/- 1.5%
      after 2 hr normothermic ischemia, 77.1 +/- 7.7% after 3 hr, 41.8 +/- 7.6% after 3
      1/2 hr, and 10.7 +/- 8.7% after 4 hr. Histology confirmed the NBT findings at 24
      hr and showed considerable regeneration of muscle fibers 1-2 weeks after injury.
      The injury caused by 3 1/2 hr normothermic ischemia is the most suitable baseline
      for study of the effects of pharmacological agents in ischemic muscle injury.
      Further study of the effects of 3 1/2 hr ischemia by a quantitative Evan's blue
      method revealed a rapid increase in vascular permeability commencing at the start
      of reperfusion and lasting for 5-6 hr. Vascular labeling with saccharated ferric
      oxide showed widespread labeling of venules within the injured muscle and
      electron microscopic examination showed severe injury to both leaking and
      nonleaking small blood vessels. However, increased vascular permeability
      accounted for only a small part of the increase in weight of ischemic muscle.

PMID- 1383615
TI  - Exocrine pancreatic function in obstructive jaundice rats: studies with isolated
      dispersed pancreatic acini.
AB  - This study was conducted to investigate pancreatic exocrine function and
      pancreatic growth in rats with obstructive jaundice (OJ). OJ was produced in
      adult male Sprague-Dawley rats by bile duct ligation; control rats underwent
      laparotomy only. Induction of OJ was associated with significant hyperplasia and
      hypertrophy of the pancreas in rats as shown by increased DNA and RNA contents of
      pancreatic tissue. Factors associated with pancreatic growth in OJ rats were
      further examined in isolated dispersed pancreatic acini from OJ rats and the data
      were compared with those for control rats. Studies with isolated dispersed acini
      from OJ rats showed that pancreatic growth was accompanied by significant
      increases in total cellular amylase content; however, amylase release (percentage
      of initial) in response to cholecystokinin octapeptide was significantly
      decreased in OJ rats compared to control rats. Total amylase output in response
      to 100 pM cholecystokinin (CCK) was higher in the OJ group when compared to the
      control group (8.6 U/mg protein versus 6.4 U/mg protein), as calculated from the
      total amylase content and percentage of amylase released. Receptor binding data
      showed that the capacity of CCK receptors in OJ rats was significantly lower when
      it was compared with control. In addition, plasma levels of CCK were
      significantly elevated in OJ rats when compared to controls. These results
      suggest that obstructive jaundice induces pancreatic growth that is associated
      with alteration of exocrine pancreatic function. Abnormally high levels of stored
      amylase in pancreatic acini may be implicated in the development of pancreatitis
      as often seen in obstructive jaundice patients.

PMID- 1383616
TI  - Effects of antifibrinolytic agents on the life span of fibrin sealant.
AB  - Fibrin sealant, a biologic glue consisting of fibrinogen and thrombin, has been
      used in a variety of surgical procedures. The usefulness of fibrin sealant may be
      prolonged by the addition of antifibrinolytic agents. This study compared the
      efficacy of transexamic acid (30 mg/ml), epsilon-aminocaproic acid (25 mg/ml),
      and aprotinin (3000 KIU/ml) to provide data on the choice of an appropriate
      antifibrinolytic agent for use with fibrin sealant. By use of a modified in vitro
      plasma euglobulin lysis time (hours), all agents were found to be superior (n =
      10 for each agent, P < 0.05, analysis of variance for completely randomized
      design followed by Dunnett's test for multiple comparisons) to control. Lysis
      times (mean +/- SE) were (control) 50.9 +/- 0.5, (tranexamic acid) 402.6 +/-
      25.4, (epsilon-aminocaproic acid) 433.5 +/- 21.2, and (aprotinin) 393.9 +/- 26.0.
      Using the in vivo implantation of fibrin sealant supplemented with 125I
      fibrinogen in the rat peritoneum significant improvement in percentage clot (mean
      +/- SE) remaining was found (P < 0.05, analysis for repeated measures followed by
      tests for multiple comparisons) under the following conditions: at 3 hr by weight
      (n = 15), tranexamic acid (70.13 +/- 2.02%) was superior to aprotinin (61.22 +/-
      2.21%) and control (61.28 +/- 2.36%); at 3 hr by radioactivity counts (n = 19),
      tranexamic acid (76.29 +/- 0.75%) was superior to epsilon-aminocaproic acid
      (72.52 +/- 1.28%) and aprotinin (73.84 +/- 0.78%); at 72 hr by radioactivity
      counts (n = 10), aprotinin (27.30 +/- 2.45%) was superior to epsilon-aminocaproic
      acid 19.76 +/- 3.09% and control (20.38 +/- 3.01%). These data suggest the early
      (3-hr) superiority of tranexamic acid as an inhibitor of plasminogen activation
      and the late (72-hr) effectiveness of aprotinin as an inhibitor of plasmin. The
      possibility of a synergistic effect of tranexamic acid and aprotinin is
      suggested.

PMID- 1383617
TI  - Contractile actions of endothelin-1 in isolated helical strips from rat pulmonary
      artery: potentiation of serotonin-induced contraction.
AB  - Endothelin-1 (ET-1) caused a concentration-dependent contraction of helical
      strips from rat pulmonary arteries. Removal of endothelial cells did not change
      the response to ET-1. ET-1 (10(-8) M) induced a small contraction of the arterial
      strips in the absence of extracellular Ca2+ (31.0% of the contraction in the
      presence of extracellular Ca2+). Pretreatment of pulmonary arterial strips with 6
      x 10(-11) M ET-1 potentiated the serotonin-induced contraction (10(-7)-3 x 10(-6)
      M), but showed no significant effect on KCl-induced contraction. The ET-1-induced
      potentiation of the response to serotonin was prevented by nordihydroguaiaretic
      acid (3 x 10(-6) M), quinacrine (10(-6) M), and AA861 (10(-6) M), but not by
      indomethacin (10(-7) M) and baicalein (10(-6) M). These results suggest that ET-1
      may cause pulmonary hypertension through a direct vasoconstrictor action and
      potentiation of serotonin-induced contraction, which may involve the 5
      lipoxygenase pathway.

PMID- 1383618
TI  - Quality of life on antihypertensive therapy: a double-blind trial comparing
      quality of life on pinacidil and nifedipine in combination with a thiazide
      diuretic. European Pinacidil Study Group.
AB  - The quality of life (QL) was evaluated in a 6 month double-blind trial in six
      European countries. Patients with a sustained supine diastolic blood pressure
      (SDBP), phase V, of 95 mm Hg or more on bendrofluazide, 5 mg daily (or an
      equivalent dose of a thiazide diuretic) were randomised to additional pinacidil
      (n = 127), 25 mg up to 100 mg daily, or nifedipine (n = 130), 20 mg up to 80 mg
      daily. The treatment groups were similar at entry for QL scores, average DBP of
      103 +/- 6 (SD) mm Hg, and average age of 56 +/- 10 (SD) years. Eighteen patients
      on pinacidil and 12 on nifedipine withdrew due to side effects, such as oedema
      (both drugs) and flushing (nifedipine). The maximum antihypertensive effect was
      achieved within 6 weeks and maintained, resulting in a significant fall in SDBP
      of 13.7 mm Hg on pinacidil and 15.5 mm Hg on nifedipine at the end of the trial.
      There was no significant difference in the antihypertensive effect. The target
      SDBP was achieved in 57% of pinacidil-and 63% of nifedipine-treated patients. The
      average number of symptomatic complaints fell in both groups, with significant
      decreases in the reporting of blurred vision and headaches on nifedipine.
      Complaints of growth of body and facial hair increased on pinacidil but there
      were no significant between-drug comparisons with respect to side effects. In
      measures of psychological well being, patients on pinacidil showed a significant
      (p less than 0.05) improvement in total and cognitive function scores compared to
      nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383619
TI  - Comparison of KRN2391 with nicorandil and nifedipine on canine coronary blood
      flow: antagonism by glibenclamide.
AB  - The mode of action of KRN2391 [N-cyano-N'-(2-nitroxyethyl)-3-
      pyridinecarboximidamide monomethanesulfonate] in coronary circulation was
      examined in anesthetized dogs in comparison with those of nicorandil and
      nifedipine. Administration of KRN2391 (10 micrograms/kg i.v.), nicorandil (300
      micrograms/kg i.v.), and nifedipine (3 micrograms/kg i.v.) caused an increase in
      coronary blood flow (CBF) and decreases in mean blood pressure (MBP) and in
      coronary vascular resistance (CVR). Heart rate (HR) was slightly and
      simultaneously increased by the drugs. Glibenclamide (5 mg/kg i.v.) blocked the
      changes of these parameters caused by KRN2391 and nicorandil, but not those
      caused by nifedipine. The present study suggests that the mechanism of action
      through ATP-sensitive K channels which are blocked by glibenclamide may
      contribute, at least in part, to the effects of KRN2391 and nicorandil on CBF and
      blood pressure (BP).

PMID- 1383620
TI  - Relationship between the sympatholytic action of nebivolol and hypotension.
AB  - Nebivolol, a chemically novel beta 1-adrenoceptor antagonist, acutely lowers
      blood pressure in spontaneously hypertensive rats, anaesthetised normotensive
      dogs, and hypertensive patients. We have investigated the actions of dl-nebivolol
      in five conscious normotensive rabbits (sham, mean blood pressure (BP) of 82.2 +/
      4.1 mm Hg, mean +/- SEM) and four hypertensive rabbits (renal wrap hypertension)
      (wrap, mean BP of 117.6 +/- 1.5 mm Hg). Nebivolol (1 mg/kg i.v.) did not
      significantly lower the BP or heart rate in either group 30 min after injection.
      In the same rabbits, on another day, after autonomic blockade (mecamylamine),
      nebivolol (0.1, 0.3, and 1.0 mg/kg i.v.) right shifted the bolus i.v.
      isoproterenol tachycardia dose-response curves by dose ratios of 5, 18, and 90 in
      sham rabbits, respectively, and 5, 11, and 23 in wrap rabbits, respectively,
      indicating significant cardiac beta 1-adrenoceptor antagonism. In guinea pig
      isolated right atria pretreated with atropine (1 microM) and desipramine (DMI,
      0.1 microM), norepinephrine concentration-response curves were antagonised
      competitively by nebivolol (3-100 nM), giving a pKb of 7.90. In separate atria
      without DMI pretreatment, neither nebivolol (100 nM) nor propranolol (100 nM) had
      any significant effect on the increase in the rate of norepinephrine efflux
      following electrical field stimulation (0.5-2 Hz, 3 min). These findings suggest
      that at concentrations of nebivolol that show substantial beta 1-adrenoceptor
      antagonism, there is no evidence of hypotension or bradycardia nor additional
      effects on cardiac norepinephrine release. Why nebivolol lowers blood pressure in
      some species but not in the conscious rabbit is not known.

PMID- 1383621
TI  - Autonomic nervous system dysfunction alters drug effects: implications for
      testing drugs for the treatment of heart failure.
AB  - Blunted cardiac responses to sympathetic and vagal activation are key features of
      heart failure. Since the modulation of drug effects by a selective autonomic
      dysfunction is little known, we developed an acute rabbit model imitating these
      defects. Anesthetized rabbits were subject to cervical vagotomy and propranolol
      (1 mg/kg i.v.) pretreatment, thus eliminating vagally and sympathetically
      mediated cardiac responses, while maintaining the responsiveness of the
      peripheral circulation to these reflexes ("V-B" animals). Responses to drugs were
      altered in V-B compared with normal animals: Ouabain (5-50 micrograms/kg)
      increased myocardial contractile force more and milrinone (30-300 micrograms/kg)
      less, yet it increased the heart rate more; the reflex tachycardia to
      nitroprusside (1-10 micrograms/kg/min) was blunted and spirapril (0.1 and 1
      mg/kg, all i.v.) decreased the central venous pressure only in V-B animals.
      Several drug effects were thus strongly modulated by autonomic dysfunction and
      responses of V-B animals were closer to those of heart failure patients than the
      responses of the normal animals, especially for milrinone.

PMID- 1383622
TI  - Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina
      pectoris patients treated with beta-blocker or diltiazem.
AB  - Ranolazine (RS 43285) is a new piperazine derivative with anti-ischemic
      properties attributed to a modulation of myocardial metabolism. Its antianginal
      action was assessed in 104 patients recruited in a double-blind, crossover,
      randomized study comparing placebo with a single dose of ranolazine (10, 60, 120,
      and 240 mg). All patients had chronic stable angina pectoris and remained
      symptomatic (at least 0.1 mV ST-segment depression and angina during prestudy
      exercise testing) despite treatment with a beta-blocker or with diltiazem. No
      significant effects of ranolazine on exercise duration or time to angina were
      observed after the dose of 10, 60, and 120 mg. After the 240 mg dose, however,
      significant improvement in exercise duration (+13.1% in the combined group, two
      tailed p = 0.002; +14.3% in the beta-blocker group, p = 0.009; +11.9% in the
      diltiazem group, p = 0.06), in time to angina (+56.8 s, p = 0.008), and in time
      to 1 mm ST-segment depression was observed. The cumulative proportion of patients
      who improved their time to angina by at least 30 s above placebo were 25, 42, 50,
      and 72% with the doses of 10, 60, 120, and 240 mg, respectively. Sixty-seven
      percent of the patients with ranolazine plasma levels above 500 ng/ml improved
      their time to angina against 40% at plasma levels below 500 ng/ml and summed ST
      segment depression during exercise and recovery was also significantly reduced at
      these plasma concentrations. Both heart rate and arterial pressure at rest and at
      peak exercise were unchanged after ranolazine, 240 mg.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1383623
TI  - Pharmacology of idrapril: a new class of angiotensin converting enzyme
      inhibitors.
AB  - Idrapril is the prototype of a new chemical class of angiotensin converting
      enzyme (ACE) inhibitors, the hydroxamic non-amino acid derivatives. Idrapril
      strongly inhibited rat and human plasma ACE and rabbit lung ACE (IC50: 7-12 nM)
      as well as the pressor response induced by angiotensin I in anesthetized rats
      (ED50: 63 nmol/kg i.v.). Idrapril (0.04-23 mumol/kg i.v.) lowered the blood
      pressure dose dependently, up to 20-35%, in different models of hypertension
      (sodium-depleted spontaneously hypertensive rat, two-kidney-one-clip renal
      hypertensive rat, and aortic-coarctated rat), its profile being similar to that
      of captopril in terms of potency and efficacy. Idrapril and captopril reduced the
      blood pressure and potentiated substance P-induced bronchoconstriction in the
      guinea pig to the same extent, suggesting a similar degree of ACE inhibition in
      the circulation. However, idrapril potentiated capsaicin-induced
      bronchoconstriction (a model that has been related to the liability of ACE
      inhibitors to produce cough in patients) less effectively than captopril. We
      conclude that effective ACE inhibition in vitro and in vivo can be obtained with
      this novel class of compounds.

PMID- 1383625
TI  - Acute improvement of cardiac function with intravenous L-propionylcarnitine in
      humans.
AB  - As the myocardial carnitine content, a key control factor in myocardial oxidative
      metabolism and energy transfer, is reduced in heart failure, administration of L
      propionylcarnitine (LPC), a potent analogue of L-carnitine, potentially may
      improve cardiac function, possibly through a positive inotropic effect. As its
      hemodynamic profile is unknown in humans, 32 fasting normotensive patients with
      coronary artery disease received either 15 mg/kg of LPC (n = 16) or vehicle
      (mannitol/acetate, n = 16) infused over 5 min. Hemodynamic, radionuclide [peak
      ejection and filling rates (PER and PFR, respectively)], and metabolic variables
      (myocardial O2, lactate, and carnitine uptake) were studied at baseline and 1, 3,
      5, 10, 15, and 45 min postdrug. The baseline ejection fraction was depressed in
      LPC patients (40 +/- 3% vs. 48 +/- 4% in the vehicle group, p less than 0.05) as
      a result of a significant high incidence of previous infarctions. Immediately
      following LPC, the cardiac total carnitine uptake changed from 102 +/- 181 to
      5,335 +/- 1,761 mumol/L (p less than 0.05). In both groups, left ventricular
      systolic and end-diastolic pressures increased significantly by 5 and 20%,
      respectively, during the first 5 min. In the vehicle group, contractility
      decreased by 5%, accompanied by a significant 11% fall in the stroke volume. In
      contrast, following LPC, isovolumetric contractility indices remained unaltered.
      Instead, both the PER and PFR improved by 16% at 45 min. Moreover, the cardiac
      output increased by 8%. LPC did not affect systemic or coronary hemodynamics.
      Lactate uptake increased by 42%, but myocardial O2 consumption did not
      change.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383624
TI  - Long-term treatment with trandolapril opposes cardiac remodeling and prolongs
      survival after myocardial infarction in rats.
AB  - Long-term treatment with angiotensin I converting enzyme inhibitors (ACEIs)
      prolongs survival in rats developing congestive heart failure after myocardial
      infarction (MI). In this experimental model, we investigated at regular intervals
      the effects of a 1-year oral treatment with trandolapril, a new ACEI, on (a)
      survival rate and duration and (b) hemodynamic, biological, and cardiac and
      vascular histomorphological parameters. Control MI rats and sham-operated
      trandolapril-treated and control rats were simultaneously studied. In MI rats,
      trandolapril significantly increased the survival rate and duration, increasing
      the life expectancy by approximately 6 months. It also significantly decreased
      the arterial blood pressure and increased diuresis. These effects occurred as
      soon as the treatment was started and persisted throughout the study.
      Trandolapril significantly limited the development of myocardial hypertrophy,
      decreasing the heart weight and left ventricular hypertrophic area and increasing
      the left ventricular myocyte nuclear density, but these effects, starting after 3
      6 months, were delayed compared to the hemodynamic ones. Finally, trandolapril
      limited the development of myocardial (both subendocardial and subepicardial) and
      aortic fibrosis. It is concluded that the early pre- and afterload effects of
      trandolapril are initially responsible for its beneficial action on survival,
      whereas later the drug's antihypertrophic and antifibrotic properties together
      with persistent hemodynamic effects account for the prolonged survival
      improvement.

PMID- 1383626
TI  - Cardiovascular effects of R- and S-enantiomers of Ro 22-9194, (2R)-2-amino-N-
      (2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate and (2S)-2
      amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide L-tartrate, in
      dog heart preparations.
AB  - A newly synthesized compound, Ro 22-9194, relates in part of to the chemical
      structure of lidocaine. The cardiac effects of R- and S-enantiomers of Ro 22-9194
      were investigated on isolated right atrial and left ventricular (LV) preparations
      which were cross-perfused with blood from another donor dog and an anesthetized
      open-chest dog. Each enantiomer (1-1,000 micrograms) decreased dose-dependently
      the sinus rate and atrial developed tension in the isolated right atrium (RA).
      The negative chronotropic responses to R- and S-enantiomers were not
      significantly different, and the negative inotropic responses to R- and S
      enantiomers were also generally comparable. Both R- and S-enantiomers (10-3,000
      micrograms) also decreased the ventricular developed tension in a dose-related
      manner similarly. In neurally decentralized, anesthetized, open-chest dogs, R-
      and S-enantiomers (0.1-3 mg/kg) injected into the femoral vein dose-dependently
      prolonged atrioventricular (A-V) conduction time and decreased heart rate (HR)
      and arterial blood pressure (ABP). Each enantiomer (3 mg/kg intravenously, i.v.)
      prolonged the interval between His bundle and ventricle rather than the interval
      between atrium and His bundle. There was no significant difference between R- and
      S-enantiomer-induced negative dromotropic actions. The duration of the negative
      dromotropic response to each enantiomer (3 mg/kg i.v.) was longer than that of
      the decrease in BP. These results suggest that the negative chronotropic,
      inotropic, and dromotropic effects of R- and S-enantiomers of Ro 22-9194 are not
      stereospecific in dog heart.

PMID- 1383627
TI  - Cardiac and hemodynamic effects of intravenous R80122, a new phosphodiesterase
      III inhibitor, in a canine model of myocardial ischemia and heart failure.
AB  - The cardiac and hemodynamic effects of R80122, a new specific phosphodiesterase
      III inhibitor, were studied in a closed-chest canine model of acute global left
      ventricular ischemia complicated by heart failure. The results obtained were
      compared with those obtained with milrinone. Intravenous infusion of the
      compounds (0.005 mg/kg/min for both) was started when stable heart failure had
      developed and was continued for 50 min followed by a washout period of 60 min.
      Both R80122 and milrinone improved the function of the acutely failing heart, as
      indicated by the increase in the values of the variables related to left
      ventricular function, but differences existed. The most striking differences were
      the normalization of the left ventricular external mechanical efficiency with
      R80122, but not with milrinone, and the maintenance of aortic blood pressure
      during infusion of R80122, which decreased during infusion of milrinone.
      Milrinone tends to induce ventricular tachycardia more frequently than R80122. It
      can be concluded that R80122 and milrinone improve the function of the acutely
      failing heart, but that the changes induced by R80122 are better balanced, i.e.,
      enhancement of external mechanical efficiency with maintenance of aortic blood
      pressure.

PMID- 1383628
TI  - Cocaine depresses myocardial contractility and prolongs isovolumetric relaxation
      in conscious dogs with partial autonomic nervous system blockade.
AB  - The direct effects of cocaine on myocardial contractility and isovolumetric
      relaxation were investigated in conscious dogs (n = 8) chronically instrumented
      for measurement of hemodynamics, including left ventricular pressure (LVP) and
      subendocardial segment length. Experiments were performed in the presence of
      pharmacologic blockade of beta-adrenergic, cholinergic, and ganglionic receptors
      because cocaine indirectly produces significant alterations in systemic
      hemodynamics through central and peripheral sympathomimetic actions. Myocardial
      contractility was quantitated using the preload recruitable stroke work (PRSW)
      versus end-diastolic segment length (EDL) relationship. LVP-segment length loops
      were generated in the unsedated control state and after cocaine administration
      with use of preload reduction by abrupt inferior vena caval constriction, and
      PRSW versus EDL slope (Mw) and length intercept (Lw) were calculated. In
      addition, regional preload recruitable work area (PRWA) and stroke work at
      constant EDL (SWEDL) were also determined. Ventricular relaxation was assessed
      using a time constant of isovolumetric relaxation assuming a nonzero asymptote of
      LVP decay. Systemic hemodynamics, myocardial contractility, and isovolumetric
      relaxation were recorded and calculated before and 1, 3, 5, and 10 min after
      cocaine administration (2 mg/kg intravenously, i.v.). Mw was significantly (p
      less than 0.05) reduced by cocaine (63 +/- 8 during control to 45 +/- 8 mm Hg at
      1 min after drug administration). PRWA also reflected significant decreases in
      myocardial contractility after cocaine administration (1,800 +/- 260 during
      control to 1,200 +/- 220 mm Hg.mm2 at 1 min after drug administration). Similar
      results were observed with SWEDL (469 +/- 60 during control to 317 +/- 52 mm
      Hg.mm at 1 min after cocaine administration). All three indexes of contractile
      state demonstrated complete recovery of contractile function by 10 min after
      cocaine administration. The time constant of isovolumetric relaxation was
      prolonged by cocaine (35 +/- 2 during control to 46 +/- 3 ms at 3 min after drug
      administration), indicating impairment of diastolic function. Ventricular
      relaxation returned to control levels within 5 min after cocaine administration.
      No cocaine-induced alterations in coronary blood flow (CBF) or changes in
      calculated pressure work index (PWI, an indicator of myocardial O2 consumption)
      were observed. The present results suggest that cocaine produces direct negative
      inotropic and lusitropic effects independent of changes in myocardial O2 supply
      and demand and autonomic nervous system activity in conscious chronically
      instrumented dogs.

PMID- 1383629
TI  - Comparison of the relaxing effects of cicletanine and cromakalim on vascular
      smooth muscle.
AB  - Cicletanine inhibited the spontaneous activity of portal vein preparations (rat,
      guinea pig, and rabbit) and that produced by norepinephrine or an increase in
      external K+ concentration to 20 mmol/L in seven types of vascular smooth muscle
      preparation (portal vein of rat, guinea pig, and rabbit; aorta of rat and guinea
      pig; and iliac artery and ear artery of rabbit). The cicletanine EC50 was
      approximately 10(-4) mol/L. Contractions produced by K+ = 80 mmol/L were also
      inhibited by cicletanine in most preparations. Only in aortic strips of rat and
      guinea pig and in rabbit iliac artery were the concentration-response
      relationships for cicletanine shifted to the right, yielding EC50 values of
      approximately 3 x 10(-4) mol/L. In contrast, the inhibitory effects of the
      potassium channel opener cromakalim (BRL 34915) were completely abolished during
      K+ = 80 mmol/L treatment in all preparations. The inhibitory effect of cromakalim
      under the other test conditions (above) was completely antagonized by application
      of glibenclamide, 10(-5) mol/L, whereas this treatment had only negligible
      effects on cicletanine inhibition in most preparations. The results indicate that
      a potassium channel opening effect does not contribute significantly to the
      inhibitory effect of cicletanine on vascular smooth muscle.

PMID- 1383630
TI  - Prajmalium, an antiarrhythmic with positive inotropic effect: mechanism of action
      in rabbit single cardiomyocytes.
AB  - The propyl derivative of ajmaline, N-n-propylajamaline (prajmalium), is an
      antiarrhythmic compound that lacks the commonly reported negative inotropic
      effects of all others under clinical use. The present study was undertaken to
      establish and understand its effects at the cellular level in mammalian
      preparations. Electrical and mechanical activities were recorded from right
      ventricular strips and Na and L-type Ca currents (INa and ICaL, respectively)
      were recorded with the whole-cell patch-clamp technique in right ventricular
      myocytes freshly dissociated from rabbit hearts. Prajmalium decreased the maximal
      rate of depolarization of the action potential in a dose-dependent manner with an
      EC50 of 3 microM. This effect was use and frequency dependent. Action potential
      duration was increased by 1 microM prajamalium but decreased on applying higher
      concentrations. The force of contraction was slightly (15%) increased at 0.1
      microM, not affected at all at 1 microM and depressed by 30% at 20 microM. In
      single cardiomyocytes maintained at negative holding potentials, INa was slightly
      depressed by prajmalium at 10 nM and reduced by 75% at 10 microM. ICaL was
      increased by 30 and 20% on applying prajmalium at 1 and 10 microM, respectively;
      on the other hand, ICaL was reduced by these two concentrations of prajmalium at
      less negative holding potentials. A higher prajmalium concentration (100 microM)
      decreased ICaL at all holding potentials studies and this effect was enhanced
      with depolarization. The increase in ICaL induced by prajmalium (1 microM) was
      also observed after ICaL had been fully beta-adrenergic and P2-purinergic
      stimulated by isoproterenol (1 microM) in the presence of IBMX (100 microM) and
      ATP (10 microM). It is concluded that prajmalium is able to increase ICaL in
      rabbit ventricular cells in a voltage-dependent manner, an effect that could
      account in part for the observed lack of negative inotropism of this
      antiarrhythmic in clinics.

PMID- 1383631
TI  - Proof for piroximone's inotropic influence; can it safely be used in coronary
      artery disease? Analysis of end-systolic pressure-volume relations (conductance
      technique).
AB  - Improved contractility after applying piroximone (PIR) a new phosphodiesterase
      III inhibitor drug, is difficult to prove clinically. However, augmented
      contractility could increase the risk of myocardial ischemia when used in
      coronary artery disease (CAD). Analysis of the end-systolic pressure-volume
      relationship (ESPVR) as a load-independent parameter of the contractile left
      ventricular (LV) function allows for differentiation of PIR's effects:
      contractility vs. unloading. We therefore analyzed ESPVR and LV function in 16
      CAD patients before and after PIR, 0.75 mg/kg intravenously. Emax increased by
      39% (9/16 patients) and loops of the ESPVR (16 patients) moved leftward,
      indicating improved contractility. The difference in percent change PIR versus
      control (16 patients) demonstrated augmentation of LV function via unloading: LV
      volumes decreased (ESV by 37%, EDV by 19%), LV-filling pressure by 34%, and
      systemic vascular resistance by 19%; dP/dtmax increased by 28%, LV efficiency by
      24%, cardiac index by 21%, and ejection fraction by 13%. Pacing-induced anginal
      threshold increased by 47% after PIR while the ischemic postpacing LV-filling
      pressure and ST-segment changes tended to normalize under the drug's influence.
      Thus, PIR improved LV function both by unloading and by positive inotropy. Lack
      of PIR-induced angina and an increased anginal threshold indicate that the drug
      can be used safely in CAD patients as well. The analysis of ESPVR proved to be
      safe and reliable in identifying contractility during the diagnostic cardiac
      catheterization routine.

PMID- 1383632
TI  - The calcium antagonist nisoldipine improves the functional recovery of reperfused
      myocardium only when given before ischemia.
AB  - It is unclear whether the protective effects of calcium antagonists on reperfused
      myocardium are secondary to increased blood flow during ischemia (anti-ischemic
      action) or reperfusion (Gregg phenomenon), or are mediated through altered
      calcium kinetics in ischemic or reperfused myocardium. To study the effect of the
      calcium antagonist nisoldipine on the functional recovery of stunned myocardium,
      32 enflurane-anesthetized dogs were subjected to 15 min of occlusion of the left
      circumflex coronary artery and subsequent 4 h of reperfusion. Eight dogs served
      as placebo controls (group I), and eight dogs received nisoldipine (5
      micrograms/kg i.v.) before occlusion (group II), eight dogs at 10 min of
      occlusion (group III), and eight dogs at 4 min of reperfusion (group IV). The
      mean aortic pressure was kept constant with an intra-aortic balloon, and the
      heart rate did not change. In group I, posterior systolic wall thickening (WT,
      sonomicrometry) decreased from 18.3 +/- 2.4% (mean +/- SD) during control
      conditions to -3.0 +/- 2.0% at 13 min of occlusion. At 10 min of reperfusion, WT
      was 1.7 +/- 3.9% and did not recover further (-1.2 +/- 3.7% at 4 h of
      reperfusion). Posterior transmural blood flow (BF, colored microspheres)
      decreased from 1.42 +/- 0.43 ml/min/g during control conditions to 0.26 +/- 0.08
      ml/min/g at 13 min of occlusion. BF was 2.07 +/- 0.93 ml/min/g at 10 min and 0.95
      +/- 0.31 ml/min/g at 4 h of reperfusion. In groups III and IV, the WT and BF were
      not different from those in group I throughout the experimental protocol. In
      group II, however, the WT, although similar to the WT of group I before and
      during ischemia, recovered from 2.7 +/- 4.3% at 10 min to 11.8 +/- 6.0% at 4 h of
      reperfusion (p less than 0.05 vs. groups I, III, and IV). The BF in group II
      decreased from 2.52 +/- 0.66 ml/min/g after administration of nisoldipine to 0.22
      +/- 0.14 ml/min g at 13 min of occlusion. The BF was 1.31 +/- 0.51 ml/min/g at 10
      min and 1.33 +/- 0.43 ml/min/g at 4 h of reperfusion. Nisoldipine exerts no
      beneficial effect when given immediately before or after the onset of
      reperfusion. The improved functional recovery of reperfused myocardium in dogs
      pretreated with nisoldipine cannot be attributed to an increased regional
      myocardial blood flow during ischemia or reperfusion. The better myocardial
      recovery, therefore, appears to be related to an attenuated myocardial calcium
      overload during the first few minutes of ischemia.

PMID- 1383633
TI  - Hemodynamic and endocrine changes associated with hypotensive action of
      amosulalol in essential hypertension.
AB  - To clarify the hemodynamic and endocrine mechanisms of the hypotensive effect of
      amosulalol, an alpha- and beta-adrenoceptor antagonist, 19 patients with
      essential hypertension received amosulalol (20-80 mg/day; average 48.4 mg/day)
      for 16 weeks. Mean blood pressure (MBP) was significantly decreased (105 +/- 1
      vs. 120 +/- 1 mm Hg, p less than 0.001), associated with a decrement in heart
      rate (HR). Although both cardiac index (CI, 3.68 +/- 0.09 vs. 3.91 +/- 0.09
      L/min/m2, p less than 0.001) and total peripheral resistance index (TPRI, 2,271
      +/- 78 vs. 2,441 +/- 79 dynes.s.cm-5.m2, p less than 0.001) were reduced, changes
      in TPRI positively correlated with those of MBP (r = 0.9155, p less than 0.001)
      but the change in CI did not (r = 0.3568, NS). Plasma renin activity (PRA, 0.55
      +/- 0.09 vs. 0.95 +/- 0.14 ng/ml/h, p less than 0.05) and aldosterone
      concentration (4.6 +/- 0.4 vs. 8.6 +/- 0.5 ng/dl, p less than 0.001) were also
      decreased with amosulalol. Thus, the hypotensive effect of amosulalol may be due
      mainly to vasodilation by alpha 1-blocking action. In addition, this hypotensive
      effect may be facilitated by either beta-blocking action such as decreased
      cardiac output (CO), with suppression of reflex tachycardia or of the renin
      angiotensin-aldosterone system.

PMID- 1383634
TI  - Synergistic effect on reduction in blood pressure with coadministration of the
      renin inhibitor, CP-80,794, and the angiotensin converting enzyme inhibitor,
      captopril.
AB  - The effects of coadministration of a renin inhibitor, CP-80,794, and an
      angiotensin converting enzyme inhibitor, captopril, on blood pressure of sodium
      depleted guinea pigs was studied. Dose-response curves for CP-80,794 (0.3-3.0
      mg/kg i.v.) and captopril (0.03-1.0 mg/kg i.v.) were obtained either alone or in
      the presence of a submaximal dose of the other inhibitor. The hypotensive
      response calculated for each compound individually was subtracted from the
      combined dose response. The results showed that statistically significant synergy
      with captopril and CP-80,794 occurred when the area rather than the peak drop or
      duration of change in blood pressure was measured. The degree of the synergy
      indicated that to achieve the same reduction in blood pressure, the dose of each
      drug, below the high end of its response range, could be decreased approximately
      sixfold when administered in combination. It was determined that the plasma
      pharmacokinetics of CP-80,794 were not altered during coadministration, as plasma
      concentrations of CP-80,794 were similar in the presence and absence of 0.1 mg/kg
      i.v. of captopril. These results indicate that by inhibiting sequential enzymes
      in the renin-angiotensin system, synergistic effects can be produced. The
      relative safety of each inhibitor could be improved by large reductions in dose
      when used concurrently.

PMID- 1383635
TI  - Pituitary adenylate cyclase activating polypeptide is a potent vasodilator in
      humans.
AB  - The vasodilator effect of the novel peptide pituitary adenylate cyclase
      activating polypeptide (PACAP) was investigated in humans. Forearm blood flow was
      measured in six healthy men by venous occlusion plethysmography. Infusion of
      PACAP into the brachial artery at 0.01, 0.1, 1, 3, and 10 pmol/min produced a
      dose-related increase in forearm blood flow in the cannulated arm from 2.8 +/-
      0.6 to 8.6 +/- 2.4 ml/100 ml/min at the highest dose (mean +/- SEM, p less than
      0.05). In a subsequent experiment, where the highest dose of PACAP was repeated
      after a 36 min interval, there was no tachyphylaxis of the forearm blood flow
      response, with the forearm blood flow increasing by 129 +/- 9% during the first
      infusion and 128 +/- 31% during the second infusion (N.S.). In further
      experiments, microvascular blood flow was measured by a laser-Doppler flow probe
      to compare the effects of intradermally injected PACAP, vasoactive intestinal
      polypeptide (VIP), and calcitonin gene-related peptide (CGRP). When injected into
      the skin of normal volunteers at 10(-12) to 10(-11) mol/site, each peptide caused
      a rapid flare lasting 2-3 min, which became erythematous after 5 min. At 10(-12)
      mol/site, intradermally injected PACAP and VIP caused a maximum increase in skin
      blood flow at 15 min of 379 +/- 96 and 307 +/- 121% (% increase above basal +/-
      SEM), respectively, and these responses were not significantly affected by oral
      aspirin (600 mg) taken 1.5 h beforehand. The vasodilation induced by PACAP at 10(
      12) mol/site lasted approximately 6 h, whereas the effect of the same dose of
      CGRP and VIP lasted less than 2 h. These data suggest that PACAP is a potent and
      long-lasting vasodilator in humans.

PMID- 1383636
TI  - Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with
      pressure-overload cardiac hypertrophy.
AB  - Evidence has been put forth that a number of human and experimental
      cardiomyopathies are associated with a lower myocardial carnitine content. This
      study was performed to test the hypothesis that the correction of carnitine
      derivative, propionyl-L-carnitine (PLC), may improve cardiac function. Repeated
      administration of PLC was compared to saline with respect to cardiac function in
      rats with pressure-overload cardiac hypertrophy and low myocardial carnitine
      levels. Cardiac hypertrophy was induced by abdominal aorta constriction in rats.
      Separate groups of rats were used for (a) determination of myocardial carnitine
      content, (b) evaluation of in vivo hemodynamics, and (c) evaluation of
      performance and metabolic state of Langendorff perfused hearts. Results showed
      the following: (i) The myocardial carnitine content was inversely correlated to
      cardiac hypertrophy (r = 0.68, p less than 0.05) and PLC treatment (50 mg/kg i.a.
      for 4 days) restored it to normal values (ii) The PLC effect on cardiac function
      was significantly and directly related to cardiac hypertrophy [correlations
      between heart weight and percent changes in cardiovascular parameters: cardiac
      output (CO), p less than 0.001; cardiac work (CW), p less than 0.01, stroke
      volume (SV) and stroke work (SW), p less than 0.02]. In animals with heart weight
      greater than 1,400 mg, the effect of PLC on CO, CW, SV, SW, and total peripheral
      resistance (TPR) was significantly different from that of saline (CO, CW, SV, and
      SW, p less than 0.005 each; TPR, p less than 0.05). The effect was observed 24 h
      after the first PLC administration and significantly diminished following a 4 day
      suspension of the treatment. (iii) Perfused hearts from PLC-treated rats
      displayed a significantly lower left ventricular end-diastolic pressure (p less
      than 0.01) and greater relaxation rate (p less than 0.05) than those from control
      rats. Moreover, in PLC-treated hearts, the content of creatine phosphate, ATP,
      and total adenine nucleotides (ATP+ADP+AMP; TAN) was significantly increased (CP,
      p less than 0.05; ATP and TAN, p less than 0.01 vs. control). These data show
      that PLC exerts a stimulatory activity on hearts with hypertrophy and low
      carnitine content, implying that carnitine deficiency may contribute to the
      depression of cardiac function in this model.

PMID- 1383637
TI  - Effects of inhibitors of neuronal uptake of 5-HT on sympathetic cardiovascular
      regulation.
AB  - The effect on sympathetic cardiovascular regulation of inhibition of the high
      affinity neuronal uptake of 5-hydroxytryptamine (5-HT) by fluvoxamine,
      citalopram, and fluoxetine was studied in anesthetized rabbits. The mean arterial
      pressure, postganglionic renal sympathetic nerve activity, heart rate, clearance
      of [3H]norepinephrine from plasma and the plasma norepinephrine concentration
      were measured, and from the latter two parameters the spillover of norepinephrine
      into the blood was calculated. The effect of fluvoxamine and fluoxetine on the
      uptake of [3H]5-HT into platelets was also examined. Of four increasing doses of
      fluvoxamine (0.6, 1.7, 5, and 15 mg/kg i.v.) and citalopram (0.3, 1, 3, and 9
      mg/kg i.v.), only the two highest ones decreased the renal sympathetic nerve
      activity, heart rate, and clearance of [3H]norepinephrine from plasma. Only the
      highest of four increasing doses of fluoxetine (0.2, 0.6, 1.7, and 5 mg/kg i.v.)
      inhibited sympathetic nerve activity. However, lower doses of fluvoxamine (0.6
      and 1.7 mg/kg i.v.) and fluoxetine (0.6 and 1.7 mg/kg i.v.) already markedly
      inhibited the uptake of [3H]5-HT into platelets. The data indicate that selective
      inhibition of neuronal uptake of 5-HT has no effect on central sympathetic
      regulation in anesthetized rabbits. The sympathoinhibition observed at high doses
      of fluvoxamine and citalopram is probably due to inhibition of the neuronal
      uptake of norepinephrine.

PMID- 1383638
TI  - Cisplatin-based (PVB+M) chemotherapy in good-risk and poor-risk nonseminomatous
      germ cell tumors.
AB  - Twenty-seven patients with metastatic nonseminomatous germ cell tumors were
      treated with Cisplatin, vinblastine, bleomycin, and low-dose methotrexate (PVB+M)
      combinations. Patients were divided into good-risk and poor-risk groups. All
      seven patients (100%) with good-risk factors achieved complete response, and all
      are alive disease free at a median of 70 months. In the poor-risk group, only 10
      of 20 patients (50%) achieved complete response, and seven (35%) are alive
      disease free at a median of 58 months. Eight patients, 4 in each group, were
      required to undergo surgery for removal of postchemotherapy residual masses. The
      results confirm that Cisplatin-based chemotherapy protocols are adequate to cure
      most patients with good-risk factors, and newer approaches are needed for
      patients at poor risk.

PMID- 1383639
TI  - Hepatic resection for a hepatocellular carcinoma larger than 10 cm.
AB  - Twenty-one patients with hepatocellular carcinoma (HCC) larger than 10 cm
      diameter were treated during the 18 year period from 1971 to 1988. The mean tumor
      size was 13 cm (range 10-18 cm). Nineteen patients (90.5%) had subjective
      symptoms. Eight patients (38.1%) had alpha-fetoprotein (AFP) levels over 10,000
      ng/ml, and in 18 patients (85.7%) the levels were over 20 ng/ml. Nevertheless,
      only three (14.3%) were detected by AFP. Scintigraphy before 1981 and
      ultrasonography after 1982 appears to be most helpful for detection of HCC.
      Nineteen lesions (90.5%) were localized in the right hepatic lobe. Large HCC
      showed a low incidence of histologically verified concomitant cirrhosis (33%; 7
      of 21) and a relatively well preserved hepatocellular function (indocyanine green
      test; 13.9 +/- 6.6%). Curative resection could be done for all 21 patients. There
      were three (14.3%) operative deaths. The 1-, 3-, and 5-year survival rates were
      72.2, 32.9, and 8.2%, respectively. One patient who underwent a left hepatic
      lobectomy has survived for over 5 years, with recurrence. There were 14
      recurrences (66.7%) in 21 patients: 11 were hepatic and three were in the lungs.
      In patients with large HCC, surgical resection should be done, provided the
      clinical status and hepatocellular reserves are adequate.

PMID- 1383640
TI  - In vitro effects of aprotinin on activated clotting time measured with different
      activators.
AB  - The effects in vitro of aprotinin on the activated clotting time measured with
      both celite- and kaolin-activated tubes were investigated in 21 consecutive
      patients requiring cardiopulmonary bypass. Four whole-blood samples (2 ml per
      sample) from each patient were tested simultaneously with Hemochron automated
      timing systems (International Technidyne Corp., Edison, N.J.) before, during, and
      after cardiopulmonary bypass. One tenth milliliter of either aprotinin (at a
      final concentration of 80, 120, or 180 KIU/ml) or saline solution was mixed in
      vitro with blood samples before determination of the activated clotting time.
      Aprotinin had no inhibitory effect on the activated clotting times of
      unheparinized blood. After heparin administration, aprotinin in the above
      concentrations prolonged the activated clotting times measured with celite
      activated tubes by 47% to 71%, as compared with the measurements of the activated
      clotting time without the addition of aprotinin. The activated clotting times in
      kaolin-activated tubes were not increased, however, by the in vitro addition of
      aprotinin. Our in vitro results indicate that aprotinin in concentrations from 80
      to 180 KIU/ml does not significantly enhance the inhibitory effects of heparin on
      the intrinsic coagulation system as evaluated by measurement of the activated
      clotting times in kaolin-activated tubes. The anticoagulation effect of heparin
      in patients receiving aprotinin infusion should be monitored with kaolin
      activated instead of celite-activated tubes because the celite makes the measured
      activated clotting time unreliable in patients receiving aprotinin therapy. These
      in vitro results require confirmation in vivo in patients receiving aprotinin
      therapy.

PMID- 1383641
TI  - Transfer of human chronic lymphocytic leukemia to mice with severe combined
      immune deficiency.
AB  - B chronic lymphocytic leukemia (CLL) cells were transferred into mice with severe
      combined immunodeficiency (SCID). Leukemia cells injected into the peritoneal
      cavity of these animals may survive for at least 10 weeks in vivo. In contrast,
      leukemia cells do not survive for long periods when injected intravenously.
      Despite the longevity of CLL cells injected i.p., these cells apparently do not
      migrate to other lymphoid tissues. Eight to sixteen weeks after receiving CLL
      cells, SCID mice develop human IgG autoantibodies to human red blood cells and/or
      high serum levels of human Ig. Soon thereafter, these animals develop lethal
      human B-cell tumors. In contrast to the original CLL cells, these human B-cell
      tumors are CD5-negative, have genomic DNA of Epstein-Barr virus (EBV), express
      antigens associated with latent EBV infection and have distinctive Ig gene
      rearrangements by Southern. We conclude that bystander B cells may generate
      tumors in CLL-reconstituted SCID mice that emulate the EBV-associated
      lymphoproliferations noted in SCID mice reconstituted with normal human PBL.

PMID- 1383642
TI  - Recombinant human granulocyte colony-stimulating factor enhanced cytotoxicity of
      Ara-C in Ara-C-resistant leukemic cells from a patient with biphenotypic leukemia
      in cell kinetic quiescence.
AB  - In vitro preincubation with recombinant granulocyte colony-stimulating factor(rhG
      CSF, 100 ng/ml) enhanced the cytotoxicity of 1-beta-D
      arabinofuranosylcytosine(Ara-C) in leukemic cells resistant to Ara-C from a
      patient with biphenotypic leukemia. Treatment of the cells with rhG-CSF resulted
      in a 17-fold increase in DNA synthesis, 4.6-fold increase in percentage of S
      phase, and a two-fold increase in Ara-CTP formation. Maximal effect was observed
      at 72 h of incubation. Combination chemotherapy with rhG-CSF and Ara-C to the
      patient showed remarkable cytoreduction. These results indicate that recruitment
      of resistant leukemic cells in cell kinetic quiescence is inducible by rhG-CSF
      and that it is possible enhancement of the cytotoxicity to cell cycle-specific
      drugs such as Ara-C.

PMID- 1383643
TI  - Immunocytochemical staining of neuropeptides in terminal arborization of primary
      afferent fibers anterogradely labeled and identified at light and electron
      microscopic levels.
AB  - A method is described to combine, at the ultrastructural level, horseradish
      peroxidase (HRP) anterograde tracing of primary afferents and peptide
      immunocytochemistry, using the lateral plexus of primary afferent fibers in
      laminae I-IIo of the rat dorsal horn as a model system. Free HRP was crushed
      against the dorsal roots. After a 14-h survival, animals were perfused, and the
      spinal cord was sliced at 50 microns with a Vibratome in a parasagittal plane.
      From these thick sections, camera lucida drawings of HRP-labeled fibers were
      obtained. Following osmication and Epon flat embedding, thick sections were re
      cut at 5 microns and the labeled arbors matched with those previously drawn from
      the 50-microns sections. Ultrathin sections were cut from the 5-microns semithin
      sections and directly stained on grids using a post-embedding immunogold labeling
      procedure. Single and/or double immunocytochemical staining was performed using a
      rat monoclonal antibody against substance P and a rabbit polyclonal antiserum
      against calcitonin gene-related peptide (CGRP). Immunocytochemical reactions were
      visualized using appropriate immunoglobulin G-gold conjugates and the double
      labeled synaptic boutons were matched with the varicosities previously visualized
      at the light level in the thick and semi-thin sections. The major advantages of
      this method are: (i) correlative studies at light and electron microscope level
      are made possible; (ii) tissue ultrastructure and antigenicity are adequately
      preserved so that a reliable subcellular localization of antigens under study is
      obtained; (iii) the markers used for tracing and immunocytochemistry are clearly
      distinguishable, even when present in the same nerve profile; and (iv)
      anterograde tracing can easily be combined with multiple immunolabeling.

PMID- 1383644
TI  - DiI tracing in combination with immunocytochemistry for analysis of
      connectivities and chemoarchitectonics of specific neural systems in a teleost,
      the Atlantic salmon.
AB  - An important goal in neuroanatomical research is to identify the
      neurotransmitters in specific neural pathways. One step towards this goal is to
      combine experimental neuronal tracing with immunocytochemistry. Unfortunately,
      optimal procedures for nerve tracing and immunocytochemistry are not always
      compatible. Carbocyanine compounds have recently been shown to be efficient
      tracers both in vivo and in paraformaldehyde-prefixed neural tissue. The
      possibility to apply them to prefixed tissue make them suitable for tracing of
      neural pathways that are not easily accessible in vivo. We have optimized the
      procedures for neural tracing with one carbocyanine compound, DiI (1,1'
      dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), in the CNS of a
      teleost fish, and evaluated its compatibility with different immunocytochemical
      protocols. We have compared several immunocytochemical protocols, taking into
      account cryostat and vibratome sectioning, glutaraldehyde post-fixation to
      stabilize DiI, antibodies with different capacity for tissue penetration and the
      use of detergents, and antibodies with different sensitivity to prolonged
      paraformaldehyde fixation. We have also evaluated the choice of marker for
      immunoreactivity and compared indirect immunofluorescence techniques using
      different fluorophores, and the peroxidase-antiperoxidase (PAP) technique with or
      without nickel enhancement of the diaminobenzidine reaction product. It appears
      that DiI tracing of neural connections in the teleost CNS yields very consistent
      results and that the combination with immunocytochemistry is very reliable. We
      present four different basic protocols for combined DiI tracing and
      immunocytochemistry, with notes on their specific applicability. Owing to their
      reliability, the protocols may prove useful in comparative neuroanatomical
      studies of other vertebrates, particularly fish and amphibians, as well as in
      studies of developmental changes and neural plasticity in fish and amphibians.

PMID- 1383645
TI  - A new procedure for multiple intraretinal transplantation into mammalian eyes.
AB  - A new method of intraretinal grafting is described which avoids opening the globe
      and allows direct visual control of the transplant by observing placement of the
      graft through the host pupil. A microsyringe with a bevelled needle partially
      ensheathed in plastic tubing in order to limit penetration was used to inject
      dissociated donor cells into 2 to 4 pre-selected points of the sub-retinal space
      of adult rats. The needle tip was inserted through the scleral and choroidal
      tissue, and observed through the animal's pupil as it reached into the sub
      retinal space. Donor cells were then injected into several sites of the retina.
      Results, using ophthalmoscopy as well as light and electron microscopy, confirmed
      the atraumatic nature of this technique and the survival of grafted cells.
      Intraretinal injection of colloidal carbon visually illustrated the effectiveness
      of this method in covering an extended portion of the host retina. The procedure,
      which is virtually free of complications has enabled us to perform multisite
      intra-ocular grafting in a safe, easy, and reliable fashion, under direct visual
      control.

PMID- 1383646
TI  - Properties of endogenous voltage-dependent sodium currents in Xenopus laevis
      oocytes.
AB  - Endogenous voltage-dependent sodium currents were recorded using standard 2
      microelectrode techniques in Xenopus laevis oocytes. Maximal inward current
      occurred at -10 mV with an average amplitude of -279 +/- 17 nA and steady-state
      inactivation was half-maximal at a voltage of -38 +/- 0.5 mV. Currents were
      blocked by low concentrations of tetrodotoxin (TTX) with an IC50 value of 6 nM.
      These properties make the endogenous sodium current in Xenopus oocytes similar to
      sodium currents expressed following injection of mammalian brain RNA. While
      endogenous sodium channels have the potential to complicate analysis when using
      the oocyte expression system, they are only present at significant levels in rare
      batches of oocytes (less than 5%). Our results do stress the need, however, to
      reproduce results from exogenous expression studies across several batches of
      oocytes from different donors.

PMID- 1383647
TI  - Lymph nodal vital staining with newer carbon particle suspensions compared with
      India ink: experimental and clinical observations.
AB  - CH40 and CH1500AA are newly prepared carbon suspensions which were examined as
      vital staining dyes for their usefulness in visualizing lymphatics at operation
      and to blacken lymph nodes. In mice, these carbon suspensions at 0.001 ml/g of
      body weight and India ink were injected subcutaneously into the footpad of the
      right hindpaw. Regional lymph nodes were visualized and were examined
      stereomicroscopically to determine how intensely these nodes blackened with
      carbon suspensions. Compared with India ink, CH40 and CH1500AA blackened the
      regional lymph nodes much faster and more vividly (1-8 min. after subcutaneous
      injection). As analyzed by centrifugal particle size distribution, CH40 and
      CH1500AA are narrowly distributed with a small particle size (150 and 167 nm,
      respectively, in mean diameter). By contrast, India ink is comprised of widely
      distributed and relatively large particles in suspension (mean diameter--254 nm).
      In 10 patients undergoing radical gastrectomy for treatment of stomach cancer,
      CH40 blackened 69% of regional lymph nodes with metastases (38 of 55) and 76% of
      those nodes without metastases (387 of 512).

PMID- 1383648
TI  - Lack of c-kit proto-oncogene rearrangement in patients with acute lymphoblastic
      leukemia (ALL) and the t(4;11)(q21;q23) translocation.

PMID- 1383649
TI  - Flow cytometric characterization of acute myeloid leukemia: IV. Comparison to the
      differentiation pathway of normal hematopoietic progenitor cells.
AB  - Gradual increase of CD38 on cells expressing CD34 characterizes the early cell
      differentiation pathway of normal human hematopoietic progenitors. In this study
      the coordinated expression pattern of CD34 and CD38 was assessed on leukemic
      blasts from bone marrow aspirates of 95 patients with newly diagnosed acute
      myeloid leukemia (AML). Expression was divided into six categories analogous to
      the differentiation pathway of normal bone marrow. The CD38 antigen was expressed
      on the leukemic cells of all patients and CD34+ leukemic cells were found in 79
      patients (83%). In 93 patients, the leukemic cells were found along the
      differentiation pathway defined by CD34 and CD38. In 33 of the 93 patients, a
      part of the CD34+ cells did not express the CD38 antigen (categories 1 and 2). In
      another 33 patients, all CD34+ cells expressed CD38 (categories 3 and 4). In the
      remaining 27 patients, only cells were found which dimly expressed CD34 or did
      not express CD34 (categories 5 and 6). Of the 93 patients, 88 were treated with
      intensive chemotherapy according to the protocol of the German AML Cooperative
      Group. Of these, 21 died early and were not evaluable for treatment response.
      Complete remission was achieved in 14 of 22 patients (64%) in categories 1 and 2,
      in 19 of 26 patients (73%) in categories 3 and 4, and in 18 of 19 patients (95%)
      in categories 5 and 6. The event-free survival was significantly longer in
      patients of categories 5 and 6 compared to patients in categories 1 and 2 (p less
      than 0.01) and categories 3 and 4 (p less than 0.05), respectively. We conclude
      that in the majority of AML patients the immunophenotype of leukemic cells
      follows the early cell differentiation pathways defined by coordinated expression
      of CD34 and CD38 similar to that of normal hematopoietic progenitors. The
      presence of cells in the late cell differentiation stages (CD34+/-, CD38 /+)
      identifies patients with a higher complete remission rate and longer complete
      remission duration.

PMID- 1383651
TI  - New therapies for benign prostatic hyperplasia.

PMID- 1383650
TI  - Transurethral microwave thermotherapy for prostatism: early Mayo Foundation
      experience.
AB  - As part of a multicenter investigative trial, transurethral microwave
      thermotherapy of the prostate was used in 60 men with symptomatic benign
      prostatic hypertrophy. A single office treatment on the Prostatron, a device that
      provides concurrent microwave heating of the prostate and conductive cooling of
      the urethra, was well tolerated and caused no major adverse events. Symptomatic
      improvement, especially the decrease in nocturia and urgency, was dramatic, and
      urinary flow was improved at 6 weeks. Continued follow-up suggests that further
      improvement will be achieved and that transurethral microwave thermotherapy has a
      role in the treatment of benign prostatic hypertrophy.

PMID- 1383652
TI  - [Simple and safe nerve block aided by computer tomography].

PMID- 1383653
TI  - [A new vaccine against hepatitis A can substitute gamma globulin prevention for
      travellers abroad].

PMID- 1383654
TI  - [Is the debate on automobile driving taboo among physicians?].

PMID- 1383655
TI  - [Palliative cancer care: a cooperation project within the EEC gives guidelines
      even for Swedish care].

PMID- 1383656
TI  - Treatment of hereditary tyrosinaemia type I by inhibition of 4
      hydroxyphenylpyruvate dioxygenase.
AB  - Liver transplantation is the only effective treatment for hereditary tyrosinaemia
      type I (McKusick 276700). We have treated one acute and four subacute-chronic
      cases with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), a
      potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27), to
      prevent the formation of maleylacetoacetate and fumarylacetoacetate and their
      saturated derivatives. The oral daily dose was 0.1-0.6 mg/kg. The excretion of
      succinylacetoacetate and succinylacetone decreased from 15-103 mmol/mol
      creatinine to the detection limit or slightly above (ie, to 20-150 mumol/mol
      creatinine). The concentration of succinylacetone in plasma decreased from 5.8-43
      mumol/l to the detection limit (0.1 mumol/l) over 2-5 months of treatment. The
      almost complete inhibition of porphobilinogen synthase in erythrocytes was
      abolished and the excretion of 5-aminolevulinate decreased to within or slightly
      above the reference range. The concentration of alpha-fetoprotein decreased in
      four patients to 1.3-7.5% of initially high values over 6-8 months. Improved
      liver function was reflected by normal concentrations of prothrombin complex and
      in decreased activities of alkaline phosphatase and gamma-glutamyltransferase in
      serum. Computed tomography revealed regression of hepatic abnormalities in three
      patients. One patient developed rickets 6 months before treatment and had
      excreted high concentrations of markers of tubular dysfunction--after 3 weeks of
      treatment, this excretion had disappeared. No side-effects were encountered.
      Inhibition of 4-hydroxyphenylpyruvate dioxygenase may prevent the development of
      liver cirrhosis and abolish or diminish the risk of liver cancer. Normalisation
      of porphyrin synthesis will eliminate the risk of porphyric crises. This type of
      treatment may thus offer an alternative to liver transplantation in hereditary
      tyrosinaemia.

PMID- 1383657
TI  - Lactate dehydrogenase changes during granulocyte colony-stimulating factor
      treatment.

PMID- 1383659
TI  - 5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal
      behaviour in schizophrenia.
AB  - Low concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5
      HIAA) in cerebrospinal fluid (CSF) are associated with suicidal behaviour in
      patients with depressive illness, but studies of the relation between CSF 5-HIAA
      and suicide in schizophrenia have been inconclusive and have not included long
      term follow-up. In a prospective study, we measured 5-HIAA in CSF taken from 30
      schizophrenic patients in a drug-free state, and followed these patients for 11
      years. 10 patients made suicide attempts during follow-up. Suicide attempters had
      significantly lower concentrations of CSF 5-HIAA at initial evaluation than non
      attempters (mean [SE] 6.7 [2.2] vs 23.6 [5.6] ng/ml, p < 0.05). Our findings
      provide further evidence of the relation between serotoninergic dysfunction and
      suicide, and suggest a role for drugs with serotoninergic effects in
      schizophrenia.

PMID- 1383658
TI  - Possible central role of nitric oxide in conditions clinically similar to
      cerebral malaria.
AB  - The changes in mental status during cerebral malaria, heat stroke, and recovery
      from major surgery are clinically similar, and are associated with high
      circulating concentrations of cytokines that can induce nitric oxide generation
      in vascular walls. This vascular nitric oxide could diffuse across the blood
      brain barrier, causing functional changes that include inhibition of glutamate
      induced calcium entry, reduced activity of the calcium-dependent nitric oxide
      synthase, and thus reduced nitric oxide formation, in post-synaptic neurons.
      Certain general anaesthetics and ethanol reduce glutamate-induced calcium entry
      into post-synaptic cells, and so would also reduce the rate of formation of
      neuronal nitric oxide. In view of the apparent importance of glutamate-induced
      nitric oxide in excitatory neurotransmission, a reduction in neuronal nitric
      oxide could help explain why these otherwise unrelated influences alter central
      nervous system function in a similar manner. In particular, this reduction could
      rationalise why heat stroke, ethanol excess, morphine poisoning, and conditions
      with high blood ammonia concentrations are easily confused clinically with
      cerebral malaria.

PMID- 1383660
TI  - Safety of anti-HCV-reactive immunoglobulin in heart transplant patients.

PMID- 1383661
TI  - Genetic susceptibility to multiple sclerosis linked to myelin basic protein gene.
AB  - Genetic factors have been implicated in the aetiology of multiple sclerosis (MS),
      but the genes conferring susceptibility to MS have not been identified. We
      carried out genetic linkage and association analyses by studying polymorphism of
      the myelin basic protein (MBP) gene on chromosome 18, a candidate gene for MS, in
      21 MS families, 51 additional unrelated patients with definite MS, and 85
      controls. All subjects were Finnish, and 14 of the families were from an area
      with an exceptional familial clustering of MS. Magnetic resonance imaging (MRI)
      was used to examine subclinical disease in symptom-free family members. In the
      association analysis, the allele frequencies between MS patients and controls
      differed significantly, p = 0.000049), the difference being attributable mainly
      to a higher frequency of a 1.27 kb allele among patients. In the linkage
      analysis, based on an autosomal dominant model and penetrance 0.05, a maximum LOD
      score of 3.42 (theta = 0.00) was obtained when patients with optic neuritis and
      their symptom-free siblings with abnormal MRI findings were classified as
      "affected". When these subjects were classified as "unknown" the maximum LOD
      scores ranged from 2.99 to 3.25 (theta = 0.00). The results suggest that in this
      population genetic predisposition to MS is closely linked to the MBP gene and
      that polymorphism at the MBP locus or an adjacent locus has a role in the
      aetiology of MS.

PMID- 1383663
TI  - The role of nitric oxide in mediating non-adrenergic non-cholinergic relaxation
      in longitudinal muscle of human taenia coli.
AB  - Electrical field stimulation (EFS) of isolated longitudinal muscle of human
      taenia coli at 4Hz produced relaxation which was abolished by tetrodotoxin but
      not adrenergic and cholinergic blockade (NANC-relaxation). NG-nitro L-arginine (L
      NOARG; 1-100 microM), an NO synthesis inhibitor, produced a concentration
      dependent partial inhibition of the NANC response; 10 microM L-NOARG inhibited
      EFS-induced relaxation by 48.6 +/- 5.20% and 100 microM L-NOARG by 54.2 +/-
      10.1%. L-Arginine (1mM), but not D-arginine (1mM) partially reversed the
      inhibitory effect and this was inversely proportional to the concentration of L
      NOARG used. Cumulative administration of NO (acidified sodium nitrite solution; 1
      100 microM) produced a concentration-dependent relaxation of the strips. L-NOARG
      (1 mM) did not affect either NO or isoprenaline-induced relaxations. These
      results provide the first preliminary evidence that NO is partially responsible
      for the NANC inhibitory transmission in the longitudinal muscle of the taenia
      coli of human colon.

PMID- 1383662
TI  - Granulocyte colony-stimulating factor for clozapine-induced agranulocytosis.

PMID- 1383664
TI  - Competitive antagonism of nitric oxide synthetase causes weight loss in mice.
AB  - These studies demonstrate that the competitive antagonist of nitric oxide
      synthesis, L-NG-nitro-arginine methyl ester (NO Arg ME), produces an L-arginine
      reversible decrease in food intake in mice. NO Arg ME also blocked the feeding
      effect of the potent orexigenic peptide, neuropeptide Y. NO Arg ME produced
      weight loss when administered over 5 days. The studies suggest that nitric oxide
      is a physiological modulator of food intake and that nitric oxide synthetase
      inhibitors may be useful in the management of obesity.

PMID- 1383665
TI  - Direct contractile effect of motilin on isolated smooth muscle cells of guinea
      pig small intestine.
AB  - We examined the direct effect of motilin on longitudinal and circular smooth
      muscle cells isolated from the guinea pig small intestine. In addition, the
      effects of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxy-benzoate hydrochloride
      (TMB-8, an inhibitor of intracellular Ca(2+)-release), verapamil (a voltage
      dependent Ca(2+)-channel blocker), and removal of extracellular Ca2+ were
      investigated to evaluate the role of intracellular Ca2+ stores and extracellular
      Ca2+ on the muscle contraction induced by motilin. The effects of atropine (a
      muscarinic receptor antagonist), spantide (a substance P receptor antagonist) and
      loxiglumide (a CCK-receptor antagonist) were also examined to determine whether
      the motilin-induced contraction was independent of those receptors. Motilin
      induced a contraction of the longitudinal and circular smooth muscle cells in a
      dose-dependent manner with the maximal effect attained after 30 seconds of
      incubation. The ED50 values were 0.3 nM and 0.05 nM, respectively. TMB-8
      suppressed completely the motilin-induced contraction of both types of smooth
      muscle cells. Verapamil had only a slight suppressive effect. Removal of
      extracellular Ca2+ did not have any significant influence on motilin-induced
      contraction. The contractile response to motilin was not affected by atropine,
      spantide or loxiglumide. Our findings showed that:1) motilin has a direct
      contractile effect on both longitudinal and circular smooth muscle cells; 2) this
      contractile effect is not evoked via muscarinic, substance P or CCK receptors,
      and 3) the intracellular release of Ca2+ plays an important role in the
      contractile response to motilin on both types of smooth muscle cells.

PMID- 1383666
TI  - Role of cAMP in the functional interaction of carbachol with different cAMP
      elevating agents in rabbit atrium.
AB  - The muscarinic agonist carbachol antagonized positive inotropic responses of
      rabbit left atria to the beta-adrenoceptor agonist isoproterenol, the adenylate
      cyclase activator forskolin and the phosphodiesterase inhibitor IBMX. Carbachol
      also reduced cAMP levels elevated by isoproterenol, but had no significant effect
      on cAMP levels in the presence of either forskolin or IBMX. Pre-treatment of
      rabbits with a dose of pertussis toxin which completely blocked the reduction by
      carbachol of isoproterenol-induced increases in cAMP, also blocked the reversal
      by carbachol of positive inotropic responses to isoproterenol, but only partially
      attenuated the antagonism by carbachol of inotropic responses to forskolin and
      IBMX. These data suggest that antagonism by carbachol of forskolin and IBMX
      induced increases in cAMP levels does not play an important role in the
      functional interaction of carbachol with these cAMP-elevating agents.

PMID- 1383667
TI  - Niflumic and flufenamic acids are potent inhibitors of chloride secretion in
      mammalian airway.
AB  - Effects of niflumic acid (NFA) and flufenamic acid (FFA), the two nonsteroid anti
      inflammatory agents recently reported to inhibit Cl- current in Xenopus oocytes,
      were examined in cultured monolayers of dog and cow trachea. Both agents showed
      potent inhibition to the short-circuit current (Isc), an index of magnitude of
      transepithelial Cl- secretion, with values of Ki of 0.02 (for NFA) and 0.06 (for
      FFA) mM, respectively. The sensitivity sequence of Isc to the Cl- channel
      inhibitors tested was NFA > FFA > diphenylamine-2-carboxylate (DPC) >> anthracene
      9-carboxylate (A9C). Thus, NFA and FFA are so far the most potent commercially
      available Cl- channel inhibitors tested in Cl(-)-secreting epithelia. The
      sensitivity sequence of 36Cl uptake to the above Cl- channel inhibitors in
      Xenopus laevis oocytes was found to be identical to the cultures of trachea. This
      seems to imply that the membrane Cl- channels of Xenopus oocytes are functionally
      similar to that identified in mammalian Cl(-)-secreting epithelia.

PMID- 1383668
TI  - Effects of dietary saturated fat on erucic acid induced myocardial lipidosis in
      rats.
AB  - Male Sprague-Dawley rats were fed for one week diets containing 20% by weight
      fat/oil mixtures with different levels of erucic acid (22:1n-9) (approximately
      2.5 or 9%) and total saturated fatty acids (approximately 8 or 35%). Corn oil and
      high erucic acid rapeseed (HEAR) oil were fed as controls. The same hearts were
      evaluated histologically using oil red O staining and chemically for cardiac
      triacylglycerol (TAG) and 22:1n-9 content in cardiac TAG to compare the three
      methods for assessing lipid accumulation in rat hearts. Rats fed corn oil showed
      trace myocardial lipidosis by staining, and a cardiac TAG content of 3.6 mg/g wet
      weight in the absence of dietary 22:1n-9. An increase in dietary 22:1n-9 resulted
      in significantly increased myocardial lipidosis as assessed histologically and by
      an accumulation of 22:1n-9 in heart lipids; there was no increase in cardiac TAG
      except when HEAR oil was fed. An increase in saturated fatty acids showed no
      changes in myocardial lipid content assessed histologically, the content of
      cardiac TAG or the 22:1n-9 content of TAG at either 2.5 or 9% dietary 22:1n-9.
      The histological staining method was more significantly correlated to 22:1n-9 in
      cardiac TAG (r = 0.49; P less than 0.001) than to total cardiac TAG (r = 0.40; P
      less than 0.05). The 22:1n-9 content was highest in cardiac TAG and free fatty
      acids. Among the cardiac phospholipids, the highest incorporation was observed
      into phosphatidylserine, followed by sphingomyelin. With the addition of
      saturated fat, the fatty acid composition showed decreased accumulation of 22:1n
      9 and increased levels of arachidonic and docosahexaenoic acids in most cardiac
      phospholipids, despite decreased dietary concentrations of their precursor fatty
      acids, linoleic and linolenic acids.

PMID- 1383669
TI  - MR imaging of benign prostatic hypertrophy using a Helmholtz-type surface coil.
AB  - MR examinations of the prostate were performed on six healthy volunteers and 18
      patients with well-documented symptomatic benign prostatic hypertrophy, using an
      organ-encompassing Helmholtz-type surface coil at 1.5 T. The healthy volunteers
      were also imaged with a standard circumferential body coil. The morphologic
      features and signal intensity characteristics of the prostate and adjacent
      structures were analyzed in the patient group. Several recognizable patterns of
      benign prostate hypertrophy were identified including bilaterally symmetrical
      nodules in the central gland, multiple central gland nodules, and a diffusely
      heterogeneous central gland without appreciable nodules. The peripheral zone was
      of moderate to high signal intensity on T2-weighted images, and was diffusely
      heterogeneous in 78% of patients. The false prostatic capsule, peripheral venous
      plexus, and seminal vesicles were also characterized. A good correlation was
      shown between prostatic glandular volume and prostate-specific antigen.
      Calculated signal-to-noise ratios (S/N) were significantly greater on images
      acquired with the Helmholtz-type receiver coil than on those acquired with the
      body coil. We conclude that the hyperplastic prostate gland has a variety of MR
      appearances, but that recognizable patterns are frequently seen. High resolution
      imaging with a Helmholtz-type surface coil provides excellent anatomical
      depiction of the prostate and adjacent structures.

PMID- 1383670
TI  - In vivo MR evaluation of Gd-DTPA conjugated to dextran in normal rabbits.
AB  - A dextran-Gd-DTPA compound has been recently synthesized utilizing 70,800 Da
      molecular weight dextran. This polymeric contrast agent for magnetic resonance
      imaging has been found chemically to be very stable and to demonstrate in vitro
      improved relaxivities of 1.5 to 2.3 times that of monomeric Gd-DTPA at 100 MHz.
      This MR experiment examines the in vivo distribution and relaxivity of the 70,800
      Da molecular weight dextran-Gd-DTPA compound in a rabbit model by measuring the
      change in signal-to-noise ratio of a variety of organs (renal cortex, renal
      medulla, liver, brain, and torcula herophile) compared to the preinjection state.
      Results demonstrate prolonged (beyond 60 min) enhancement of the renal cortex,
      renal medulla, liver and torcula, and no enhancement of brain parenchyma.

PMID- 1383673
TI  - Parallel-stranded duplex DNA.

PMID- 1383671
TI  - [Incidence of malaria and S hemoglobinopathy in the pediatric hospital milieu in
      Bamako, Mali].
AB  - A study on the incidence and gravity of malaria among children suffering of
      sickle cell anemia was carried out in the pediatric hospital of Bamako-Mali. On
      the 236 cases of fever studied, 54.2% were malaria infected and 21.2% were
      carriers of the sicklemic trait. There was a significant difference between
      malaria affecting AA children and HbS children, specially concerning parasites
      load.

PMID- 1383672
TI  - Molecular dissection of structure and function in the lipopolysaccharide of
      Rhizobium leguminosarum strain 3841 using monoclonal antibodies and genetic
      analysis.
AB  - Following treatment with nitrosoguanidine, mutant derivatives of Rhizobium
      leguminosarum strain 3841 were isolated which failed to react with AFRC MAC 203.
      This monoclonal antibody normally recognizes a strain-specific lipopolysaccharide
      epitope which is developmentally regulated during legume nodule differentiation.
      Structural modification of lipopolysaccharide (LPS) was analysed by examining
      reactivity with a range of monoclonal antibodies with different epitope
      specificities, and also by analysis of LPS mobility changes after electrophoresis
      on polyacrylamide gels. One class of these LPS-defective mutants induced normal
      nitrogen-fixing (Fix+) nodules on peas (Pisum sativum), while another two classes
      of Fix- mutants were also identified, suggesting that a component of the LPS
      antigen that is part of the MAC 203 epitope is essential for normal nodule
      development leading to symbiotic nitrogen fixation. When grown under low-oxygen
      or low-pH culture conditions, one class of Fix- mutants completely lacked LPS-1
      (the species that carries O antigen) and a second class showed a modified and
      truncated form of LPS-1. Mutants with defective LPS structure were also obtained
      after Tn5 mutagenesis of R. leguminosarum 3841 and all nine Fix- mutants were
      also found to lack the MAC 203 epitope. Three of these transposon-induced mutants
      synthesized a truncated form of LPS-1 that was structurally similar to that of
      the class of the NTG-induced mutants described above. These transposon-induced
      mutations, and the nitrosoguanidine-induced Fix- mutations, were closely linked
      and could be suppressed by the same cloned fragment of chromosomal DNA. The data
      presented here suggest that a precondition for normal nodule development of R.
      leguminosarum 3841 within pea nodules is the ability to synthesize relatively
      long-chain LPS-1 macromolecules under the physiological conditions encountered
      within the nodule. All mutants that lacked the ability to elongate LPS-1
      macromolecules also failed to express the MAC 203 epitope.

PMID- 1383674
TI  - Characteristics of sodium benzoate injury of Listeria monocytogenes.
AB  - Over 99% of viable cells of Listeria monocytogenes were injured after exposure to
      a solution of 8.5% sodium benzoate (pH 7.0) for 1 h. Injury was evident by the
      inability of the bacterium to tolerate 6% NaCl in tryptose agar (TA) and the
      ability to grow on TA with no added salt. The colony-forming ability of the
      injured cells was restored when they recovered in tryptose broth containing
      sublethal amounts of metabolic or synthetic inhibitors. Synthesis of mRNA was
      critical for restoration of salt tolerance. Inhibition of electron transport,
      protein synthesis, or repair of the cell wall did not suppress recovery of the
      cells. Changes in the cell membrane which may have occurred did not allow soluble
      proteins or nucleotides to leak during the course of benzoate injury.

PMID- 1383675
TI  - Lipopolysaccharide composition and virulence properties of clinical and
      environmental strains of Vibrio fluvialis and Vibrio mimicus.
AB  - Vibrio mimicus strains W-26768 (stool isolate) and N-1301 (environmental isolate)
      and Vibrio fluvialis strains AA-18239 (stool isolate) and M-940 (environmental
      isolate) were studied for virulence properties and lipopolysaccharide
      composition. All four strains were hydrophobic, produced cytotoxin, adhered to
      HeLa cells and showed mannose-sensitive agglutination of guinea pig erythrocyte.
      The strains were negative for enterotoxin production and were mostly susceptible
      to the common antibiotics. The environmental and clinical isolates of both
      species were antigenically unrelated to each other. Lipopolysaccharide antigen
      analysis showed that O-antigen polysaccharides of two strains of V. fluvialis and
      two strains of V. mimicus differed with respect to the sugar components. Only LPS
      from V. mimicus W-26768 showed the presence of an unusual sugar, 3,6-dideoxy-3
      acetamido-hexose. The sugar compositions of these V. fluvialis and V. mimicus
      strains differed from those of previously reported Japanese isolates. These
      differences probably reflect differences in the serogroup of strains.

PMID- 1383676
TI  - [The interaction of the causative agent of melioidosis with the host's alveolar
      macrophages].
AB  - Studies were carried out on guinea pigs and albino rats, intranasally infected
      with P. pseudomallei C-141. The cells of bronchovesicular exudate were obtained
      from animals 1, 4 and 24 hours after infection. Electron microscopy was applied
      to study the process of interaction of the agent and alveolar macrophages.
      Bacteria were shown to form a capsule which permitted avoiding phagocytosis, when
      entering the host respiratory system. Microbes that failed to form a capsule were
      absorbed by macrophages and enclosed in a phagosome. Then some bacteria were
      destroyed by the lysosomal enzymes, the other synthesized a capsule, which
      protected them against the effect of phagolysosome content. There were also such
      microbes which escaped from a phagosome prior to fusion with lysosomes and
      parasitized in phagocytic cytoplasma forming a capsule there. By the end of the
      first 24 hours of observation the intact encapsulated microbe species were found
      to prevail in the host cells.

PMID- 1383677
TI  - When the diagnosis of deafness is wrong.
AB  - OBJECTIVE: To describe three children in whom there had been major errors in the
      diagnosis of hearing loss. CLINICAL FEATURES: In three children (two
      developmentally delayed, one not developmentally delayed) hearing thresholds
      obtained by behavioural testing were later proven wrong. This resulted in
      significant family distress and inappropriate educational approaches.
      INTERVENTION AND OUTCOME: Electrocochleography and brainstem audiometry were
      performed, demonstrating normal cochlear function. Simultaneous microinspection
      of the ears gave information about current or old middle ear disease and the
      likelihood of past conductive hearing loss. In each case hearing aids could be
      discarded, enabling parents and teachers to concentrate on one rather than
      multiple problems. CONCLUSION: Electrocochleography and brainstem audiometry
      should be used more frequently to check the diagnosis of hearing loss in children
      who are developmentally delayed, hyperactive or autistic and who do not give
      consistent responses to behavioural testing. It should also be considered if
      parents are firmly convinced that the diagnosis of deafness is wrong.

PMID- 1383678
TI  - Lead: subtle forms and new modes of poisoning.

PMID- 1383679
TI  - Laser prostatectomy.

PMID- 1383680
TI  - Microbiochemical analysis of changes in proteoglycan and collagen in joint
      tissues during the development of antigen-induced arthritis in the rabbit.
AB  - Microbiochemical assays of the proteoglycan and collagen content of articular
      cartilage and synovial lining have been performed on tissue sections taken from
      rabbits with antigen-induced arthritis. This experimental arthritis is a close
      analogue of the natural disease-rheumatoid arthritis. Animals were killed at
      intervals during the first 21 days following induction of arthritis to assess
      changes in the composition of the extracellular matrices of the synovial lining
      and articular cartilage during the early development of this experimental lesion.
      In confirmation of earlier studies these microbiochemical assays revealed a rapid
      and significant loss of proteoglycan from the articular cartilage. This loss was,
      however, not uniform but was restricted to the intermediate zone of the
      cartilage. Over the period studied, there was only a slight loss of proteoglycan
      from the superficial zone of the cartilage facing the joint cavity. These
      findings demonstrate that, at least in this model, cartilage proteoglycan loss is
      not due to the action of proteases present in the synovial fluid. Moreover it
      suggests that the chondrocytes in the mid-zone of the cartilage are responsive to
      those signals stimulating proteoglycan breakdown. There was no significant loss
      of collagen from the cartilage over the time period of this study. The synovial
      lining from arthritic joints, in contrast, showed a progressive increase in both
      proteoglycan and collagen.

PMID- 1383682
TI  - Update: influenza activity--United States and worldwide, 1992.
AB  - During the 1991-92 influenza season, influenza activity was reported at moderate
      levels in many parts of the world. Influenza A(H1N1), A(H3N2), and influenza B
      viruses have continued to circulate worldwide. From October 1991 through February
      1992, when influenza viruses circulated widely in the Northern Hemisphere,
      epidemic levels of activity were most commonly associated with the H3N2 subtype
      of influenza A (1). This report summarizes worldwide influenza activity reported
      from March through September 1992 and activity in the United States from October
      1991 through September 1992.

PMID- 1383681
TI  - [Neuropsychiatric development of children with acquired immunodeficiency].
AB  - The Authors describe the neuropsychological evolution of 88 children (86 born
      from HIV infected mothers and, 2 infected by blood products) followed up at the
      Institute of Infectious Diseases of the University of Pavia. All patients had a
      clinical, serological and immunologic evaluation done by a pediatric
      infectivologist and a neurological assessment (Amyeli-Tison and Towen) done by a
      pediatric neurologist every three months. The Mental Development was examined
      using the Griffith scales. Electroencephalographic, TC scan, liquor test and
      other invasive tests were done only in symptomatic patients when indicated. The
      incidence of Central Nervous System involvement by HIV virus was 24% in infected
      patients and 37% in children with symptomatic HIV infection; neurological
      symptoms were observed in coincidence with worsening of AIDS disease. Fifty-five
      percent of the patients had a serious developmental delays. The Authors stress
      the importance of an early psychological care of these patients done by a
      specialist physician in order to reduce the onset of developmental problems in
      children facing a life expectancy longer than before due to the continuous
      improvement in the therapeutic management of AIDS.

PMID- 1383683
TI  - Reversible inactivation of a foreign gene, hph, during the asexual cycle in
      Neurospora crassa transformants.
AB  - A plasmid construct carrying the hygromycin phosphotransferase (hph) gene fused
      to the expression elements of the trpC gene of Aspergillus nidulans was used to
      obtain hygromycin B (Hyg)-resistant transformants of Neurospora crassa. The
      plasmid does not have any homology with the N. crassa genome. Here we demonstrate
      that most of the transformants arise from integration of the transforming DNA
      into only one of the nuclei present in the protoplasts. Furthermore, in most of
      the transformants the integrated transforming DNA is physically stable after
      growth of the transformants for about 25 nuclear divisions without Hyg selection,
      in spite of being present in multiple copies. In transformants carrying only a
      single insertion, phenotypic expression of the hph gene remains unaltered in
      conidial isolates obtained without Hyg selection. On the other hand, about 40% of
      transformants harbouring plasmid DNA integrated at more than one location yield
      conidial isolates showing reversible inactivation of the hph genes.
      Interestingly, the presence of methylated cytosine residues in the integrated DNA
      is strongly correlated with the number of plasmid copies. The hph genes are
      heavily methylated in transformants harbouring multiple copies but not in those
      harbouring only one copy of the plasmid. Phenotypic expression of the inactive
      hph genes can be restored by growing the transformants either under Hyg selection
      pressure or in the presence of 5-azacytidine. In the first case the hph genes are
      again inactivated when Hyg selection pressure is removed, while the activation of
      the hph gene by 5-azacytidine gives stable Hygr strains.

PMID- 1383684
TI  - Chronic ethanol administration alters gamma-aminobutyric acidA receptor gene
      expression.
AB  - Chronic ethanol (alcohol) administration has been associated with alterations in
      the binding and function of the gamma-aminobutyric acid (GABAA) receptor. To
      evaluate the mechanism underlying these changes, we measured the steady state
      levels of the mRNAs for the alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6
      subunits of the GABAA receptor after chronic ethanol administration to rats and
      ethanol withdrawal for 24 hr. The results indicated that chronic ethanol
      administration resulted in a 61% decline in the level of the GABAA receptor alpha
      1 subunit mRNAs [3.8 and 4.3 kilobases (kb)] in the cerebral cortex in rats. The
      levels of the alpha 2 subunit mRNAs (6 and 3 kb) and the alpha 5 subunit mRNA
      (2.8 kb) were also reduced, by 61, 45, and 51%, respectively, whereas there was
      no change in the level of the alpha 3 subunit mRNA (3 kb). Furthermore, the
      ethanol-induced decrease in receptor mRNA levels persisted for 24 hr, after
      withdrawal of ethanol and returned to control values at 36 hr of withdrawal.
      alpha 1 mRNA levels in cerebellum also decreased by 28%. The level of the alpha 6
      subunit mRNA, which selectively encodes Ro15-4513 binding sites, was found to be
      increased by approximately 76% in the cerebellum. Also, the photoaffinity
      labeling studies using [3H]Ro15-4513 indicated an increase in the levels of
      various protein components of the GABAA receptor, in the cerebellum and the
      cerebral cortex (e.g., 50- and 55-kDa proteins in the cerebellum and 41- and 50
      kDa proteins in the cortex), after chronic ethanol treatment. The increase in
      alpha 6 mRNA in the cerebellum might be related to the increased labeling of the
      55-kDa (approximately 56-kDa) protein and partially responsible for the increased
      binding, as reported previously by us. Because the alpha 6 subunit is not
      expressed in cortex, involvement of an as yet unknown subunit in this region
      cannot be ruled out. The effect of chronic ethanol treatment appears to be
      specific for GABAA receptor subunit mRNAs, because the same treatment did not
      alter the levels of glyceraldehyde-3-dehydrogenase mRNA or poly(A)+ RNA. In
      summary, these data indicate that chronic ethanol treatment results in an
      alteration in the regulation of expression of GABAA receptor subunit-encoding
      mRNAs, which could be due to alterations in transcription or mRNA stability.

PMID- 1383685
TI  - Characterization of the binding of a potent, selective, radioiodinated antagonist
      to the human neurokinin-1 receptor.
AB  - We have synthesized a potent, selective, radioiodinated antagonist of the human
      neurokinin-1 (NK1) receptor and have characterized its binding to the cloned
      receptor expressed in Chinese hamster ovary cells. (cis)-2-(Diphenylmethyl)-N-[(2
      iodophenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine (L-703606) inhibits binding
      of 125I-Tyr8-substance P to the human NK1 receptor with an IC50 of 2 nM. This
      compound is a competitive antagonist of substance P-induced inositol phosphate
      generation, with a Kb of 29 nM. [125I]L-703606 binds to a single class of high
      affinity binding sites in human NK1/Chinese hamster ovary cell membranes (Kd =
      0.3 nM). Substance P inhibits the binding of [125I]L-703606 to 65% of the NK1
      receptor sites with a Kd of 0.04 +/- 0.03 nM and to the remaining 35% of the
      sites with a Kd of 1.5 +/- 0.7 nM. Addition of the nonhydrolyzable GTP analog
      guanylyl-5'-(beta, gamma-imido)diphosphate [Gpp(NH)p] shifts greater than 90% of
      the binding sites to the lower affinity state. In addition, Gpp(NH)p markedly
      alters the dissociation of substance P from the NK1 receptor by increasing the
      number of sites in the low affinity, rapidly dissociating state. However,
      Gpp(NH)p does not affect the rate of dissociation of [125I]L-703606. These data
      suggest that the pharmacological properties of [125I]L-703606 binding to the
      human NK1 receptor are similar to those of antagonists of nonpeptide guanine
      nucleotide-binding protein-coupled receptors and that this ligand will be useful
      for the biochemical and pharmacological characterization of the human NK1
      receptor.

PMID- 1383686
TI  - [Statistical analysis of enhancers of a series of eukaryotic genes].
AB  - Consensus sequences of transcription factors IRF, E12/E47, MBF1 and MyoD1 were
      represented as combination of the short oligonucleotide patterns ("enhansones").
      The ad hoc computer program was employed for analysis of distribution and
      localization of these patterns on the sequences of interferons, immunoglobulins,
      metallothioneins and muscle-specific genes. The set of patterns was strictly
      specific for each gene family. In enhancer regions of almost all genes from
      mentioned families patterns were gathered in compact groups surrounding the
      operator sites. This empirical rule is true for genes where two conditions were
      fulfilled. (1) Operator site consists of tandem or inverted repeat of the short
      oligonucleotide motif, for instance GAAA-GAA in interferons or CCA-TGG in
      immunoglobulins. (2) Multiplication of the operator site leads to increase of
      enhancer activity because of cooperative interactions between transcriptions
      factors.

PMID- 1383687
TI  - The spliceosome assembly pathway in mammalian extracts.
AB  - A mammalian splicing commitment complex was functionally defined by using a
      template commitment assay. This complex was partially purified and shown to be a
      required intermediate for complex A formation. The productive formation of this
      commitment complex required both splice sites and the polypyrimidine tract. U1
      small nuclear ribonucleoprotein (snRNP) was the only spliceosomal U snRNP
      required for this formation. A protein factor, very likely U2AF, is probably
      involved in the formation of the splicing commitment complex. From the kinetics
      of appearance of complex A and complex B, it was previously postulated that
      complex A represents a functional intermediate in spliceosome assembly. Complex A
      was partially purified and shown to be a required intermediate for complex B
      (spliceosome) formation. Thus, a spliceosome pathway is for the first time
      supported by direct biochemical evidence: RNA+U1 snRNP+?U2 auxiliary factor+?Y---
      CC+U2 snRNP+Z----A+U4/6,5 snRNPs+ beta----B.

PMID- 1383688
TI  - Activation of c-Src in cells bearing v-Crk and its suppression by Csk.
AB  - The protein product of the CT10 virus, p47gag-crk (v-Crk), which contains Src
      homology region 2 (SH2) and 3 (SH3) domains but lacks a kinase domain, is
      believed to cause an increase in cellular protein tyrosine phosphorylation. A
      candidate tyrosine kinase, Csk (C-terminal Src kinase), has been implicated in c
      Src Tyr-527 phosphorylation, which negatively regulates the protein tyrosine
      kinase of pp60c-src (c-Src). To investigate how c-Src kinase activity is
      regulated in vivo, we first looked at whether v-Crk can activate c-Src kinase. We
      found that cooverexpression of v-Crk and c-Src caused elevation of c-Src kinase
      activity, resulting in an increase of tyrosine phosphorylation of cellular
      proteins and morphological transformation of rat 3Y1 fibroblasts. v-Crk and c-Src
      complexes were not detected, although v-Crk bound to a variety of tyrosine
      phosphorylated proteins in cells overexpressing v-Crk and c-Src. Overexpression
      of Csk in these transformed cells caused reversion to normal phenotypes and also
      reduced the level of c-Src kinase activity. However, Csk did not cause reversion
      of cells transformed by v-Src or c-Src527F, in which Tyr-527 was changed to Phe.
      These results strongly suggest that Csk acts on Tyr-527 of c-Src and suppresses c
      Src kinase activity in vivo. Because Csk can suppress transformation by
      cooverexpression of v-Crk and c-Src, we suggest that v-Crk causes activation of c
      Src in vivo by altering the phosphorylation state of Tyr-527.

PMID- 1383689
TI  - Activated lck tyrosine protein kinase stimulates antigen-independent interleukin
      2 production in T cells.
AB  - p56lck, a member of the src family of cytoplasmic tyrosine kinases, is expressed
      predominantly in T cells where it associates with the T-cell surface molecules
      CD4 and CD8. Mutants of CD4 and CD8 that have lost the ability to associate with
      p56lck no longer enhance antigen-induced T-cell activation. This suggests that
      p56lck plays an important role during T-cell activation. In an effort to
      understand the function of p56lck in T cells, a constitutively activated lck gene
      (F505lck) was introduced into T-helper hybridoma cell lines by retroviral
      infection. In four T-cell lines we examined, the activated lck protein stimulated
      interleukin-2 (IL-2) production, a hallmark of T-cell activation, in the absence
      of antigenic stimulation. In addition, a marked increase in antigen-independent
      IL-2 production was apparent when T cells infected with a temperature-sensitive
      F505lck were shifted to the permissive temperature. Only one cell line expressing
      F505lck exhibited increased sensitivity to antigenic stimulation. The SH3 domain
      of p56lck was dispensable for the induction of antigen-independent IL-2
      production. In contrast, deletion of the majority of the SH2 domain of p56F505lck
      reduced its ability to induce spontaneous IL-2 production markedly. Activated
      p60c-src also induced antigen-independent IL-2 production, whereas two other
      tyrosine kinases, v-abl and the platelet-derived growth factor receptor, did not.
      Tyrosine phosphorylation of a 70-kDa cellular protein was observed after cross
      linking of CD4 in T cells expressing F505lck but not in cells expressing F527src.

PMID- 1383690
TI  - A limited set of SH2 domains binds BCR through a high-affinity phosphotyrosine
      independent interaction.
AB  - SH2 (src homology region 2) domains are implicated in protein-protein
      interactions involved in signal transduction pathways. Isolated SH2 domains bind
      proteins that are tyrosine phosphorylated. A novel, phosphotyrosine-independent
      binding interaction between BCR, the Philadelphia chromosome breakpoint cluster
      region gene product, and the SH2 domain of its translocation partner c-ABL has
      recently been reported. We have examined the ability of additional SH2 domains to
      bind phosphotyrosine-free BCR and compared this with their ability to bind
      tyrosine-phosphorylated c-ABL 1b. Of 11 individual SH2 domains examined, 8
      exhibited relatively high affinity for c-ABL 1b, whereas only 4 exhibited
      relatively high affinity for BCR. Binding of tyrosine-phosphorylated c-ABL 1b by
      the relatively high-affinity ABL and ARG SH2 domains was quantitatively analyzed,
      and equilibrium dissociation constants for both interactions were estimated to be
      in the range of 5 x 10(-7) M. The ABL SH2 domain exhibited relatively high
      affinity for phosphotyrosine-free BCR as well; however, this interaction appears
      to be about two orders of magnitude weaker than binding of tyrosine
      phosphorylated c-ABL 1b. The ARG SH2 domain exhibited relatively weak affinity
      for BCR and was determined to bind about 10-fold less strongly than the ABL SH2
      domain. The ABL and ARG SH2 domains differ by only 10 of 91 amino acids, and the
      substitution of ABL-specific amino acids into either the amino- or carboxy
      terminal half of the ARG SH2 domain was found to increase its affinity for BCR.
      We discuss these results in terms of a model which has been proposed for peptide
      binding by class I histocompatibility glycoproteins.

PMID- 1383691
TI  - The Mauriceville plasmid of Neurospora crassa: characterization of a novel
      reverse transcriptase that begins cDNA synthesis at the 3' end of template RNA.
AB  - The Mauriceville and Varkud plasmids are retroid elements that propagate in the
      mitochondria of some Neurospora spp. strains. Previous studies of endogenous
      reactions in ribonucleoprotein particle preparations suggested that the plasmids
      use a novel mechanism of reverse transcription that involves synthesis of a full
      length minus-strand DNA beginning at the 3' end of the plasmid transcript, which
      has a 3' tRNA-like structure (M. T. R. Kuiper and A. M. Lambowitz, Cell 55:693
      704, 1988). In this study, we developed procedures for releasing the Mauriceville
      plasmid reverse transcriptase from mitochondrial ribonucleoprotein particles and
      partially purifying it by heparin-Sepharose chromatography. By using these
      soluble preparations, we show directly that the Mauriceville plasmid reverse
      transcriptase synthesizes full-length cDNA copies of in vitro transcripts
      beginning at the 3' end and has a preference for transcripts having the 3' tRNA
      like structure. Further, unlike retroviral reverse transcriptases, the
      Mauriceville plasmid reverse transcriptase begins cDNA synthesis directly
      opposite the 3'-terminal nucleotide of the template RNA. The ability to initiate
      cDNA synthesis directly at the 3' end of template RNAs may also be relevant to
      the mechanisms of reverse transcription used by LINEs, group II introns, and
      other non-long terminal repeat retroid elements.

PMID- 1383692
TI  - Transcription of the insulin-like growth factor-binding protein-2 gene is
      increased in neonatal and fasted adult rat liver.
AB  - The insulin-like growth factor-binding proteins (IGFBPs) are a family of proteins
      that specifically bind IGF-I and IGF-II, determine their bioavailability to
      tissues, and modulate their actions in target tissues. Levels of IGFBPs in plasma
      and IGFBP mRNAs in liver are highly regulated with developmental age and
      metabolic status. We now demonstrate that the increase in IGFBP-2 mRNA in fasted
      adult rat liver and in the liver of normal neonatal rats reflects an increased
      rate of transcription. When adult rats were fasted for 2-3 days, IGFBP-2 mRNA was
      increased in liver, but not in brain or kidney. The increase in hepatic IGFBP-2
      mRNA was observed after only 1 day of fasting. Levels decreased by half after 6 h
      of refeeding and returned to their low starting values after 2 days of refeeding.
      Transcription-elongation experiments indicated that transcription of the IGFBP-2
      gene was increased in fasted liver. The rate of transcription increased 9.2- +/-
      3.5-fold for transcripts labeled in exon 1 and 6.6- +/- 2.4-fold for transcripts
      labeled in exons 2, 3, and 4, suggesting that fasting causes a uniform increase
      in the number of RNA polymerase II molecules along the length of the IGFBP-2
      gene. We infer from these results that the regulation of IGFBP-2 gene
      transcription in fasting occurs at the level of initiation rather than
      elongation. IGFBP-2 gene transcription also was increased 3.8- +/- 1.2-fold (exon
      1) and 2.9- +/- 0.9-fold (exons 2, 3, and 4) in nuclei from 2-day postnatal rat
      liver compared with adult rat liver, consistent with the greater abundance of
      IGFBP-2 mRNA in neonatal rat liver.

PMID- 1383693
TI  - Expression of messenger RNA for kit-ligand in human placenta: localization by in
      situ hybridization and identification of alternatively spliced variants.
AB  - Kit-ligand is a novel polypeptide growth factor which binds and activates the c
      kit protooncogene, a receptor tyrosine kinase. We used the technique of reverse
      transcription-polymerase chain reaction to demonstrate the expression of this
      growth factor in human placenta. In situ hybridization showed that kit-ligand
      mRNA is expressed in cytotrophoblast and syncytiotrophoblast cells in the
      placenta, and in fetally derived extravillous trophoblast cells which have
      invaded the maternal endometrium. Five species of mRNA encoding variants of kit
      ligand were identified by nested reverse transcription-polymerase chain reaction.
      Cloning and sequencing indicate that these variants arise by alternative splicing
      of the kit-ligand transcript. One of these species, KL486, uses a novel splice
      site in exon 8. There is a different pattern of expression of the variants in
      amnion, chorion, trophoblast, and placenta, indicating tissue-specific control of
      splicing.

PMID- 1383694
TI  - Determination of B-cell epitopes of nef HIV-I protein: immunogenicity related to
      their structure.
AB  - Determination of the B-cell epitopes of the nef molecule encoded by the human
      immunodeficiency virus type 1 (HIV-1) was undertaken using a set of six synthetic
      peptides. Sequences that were both antigenic and immunogenic and stimulated the
      production of antibodies recognizing the full length molecule, were considered as
      B-cell epitopes. Two peptidic sequences were antigenic both in rodents (mice and
      rats) and in non-human primates (chimpanzee). They were located in the regions 45
      69 and 176-206 of the nef molecule. Two additional antigenic sequences were
      determined, one in chimpanzees, region 79-94, and the second in rodents, region
      148-161. Immunogenicity was investigated in the rodents. Only the 45-69 and 176
      206 sequences were immunogenic, and specific antibodies present in the sera of
      the immunized animals reacted with the nef protein. Therefore, each of these two
      sequences could be considered as containing at least one B-cell epitope. The fine
      epitopic specificity was determined using subfragments of these two sequences and
      it was shown that the antigenic determinants were contained in the C-terminal
      region of each sequence overlapping with the T-cell epitopes. These results
      raised the importance of vicinity of B- and T-cell determinants and their
      immunogenicity.

PMID- 1383695
TI  - IGM kappa/lambda EBV human B cell clone: an early step of differentiation of
      fetal B cells or a distinct B lineage?
AB  - In agreement with the clonal theory, one B lymphocyte synthesizes one antibody
      due to allelic and isotypic exclusion. We analyzed an EBV B-cell clone, E29.1,
      derived from an 11 week-old embryo, and secreting both IgM kappa and IgM lambda.
      Structural analysis of produced IgM, indicated that lambda-containing pentamers
      could be considered hybrid molecules, expressing both the kappa and lambda.
      chains, with a kappa/lambda ratio between 5 and 10. It was also found that 60% of
      the lambda chains were secreted in free form, presumably as a result of a better
      affinity of mu chains for kappa chains. The sequence of the three transcripts had
      an entirely ORF (Open Reading Frame), and were very close to germline sequences,
      with, however, an additional codon between V kappa and J kappa gene which has
      never been described in adult myeloma protein or cDNA human sequence. This
      observation is suggestive of N diversity taking place in kappa chains. The
      possible role of Kde (kappa deleting element) recombination onto kappa/lambda
      locus activation was analyzed on a collection of 23 lambda clones. The status of
      rearrangement of kappa genes indicated that 35% of these clones had retained, at
      least, one kappa allele without the Kde recombination, four lambda clones had one
      kappa allele in germline configuration. Different hypotheses of maturation from
      pre-B cell to B cell with activation of light chain genes are discussed.

PMID- 1383696
TI  - Amino acid sequence requirements for the epitope recognized by a monoclonal
      antibody reacting with the secreted antigen GP28.5 of Toxoplasma gondii.
AB  - We have characterized in detail, the epitope of the secreted antigen GP28.5
      recognized by the mouse monoclonal antibody TG 17-179 using synthetic peptides
      and a truncated recombinant fusion protein. The screening of a T. gondii
      expression library with TG17-179 mAb led to the isolation of cDNAs clones, all
      encoding for the C-terminal region of GP28.5 and with one encoding for only the
      five last C-terminal residues. Competitive ELISA with longer peptides revealed
      that the immunoreactivity was retained for peptides of eight residues or longer,
      and lost when the peptide was reduced to the six last C-terminal residues or
      less. Experiments with the octapeptide lacking the carboxy-terminal glutamine
      residue showed it to be 64-fold less active. Moreover, neither addition of
      residues in the carboxy-end nor substitution of COOH function changed the
      immunoreactivity of the epitope. Competition experiments between TG17-179 mAb and
      sera from infected individuals demonstrates that the epitope defined by a mouse
      monoclonal probe is also a major epitope for human polyclonal antibodies. These
      results describe the sequence requirements within a probably linear epitope and
      give rise to some general question concerning experimental test for epitope
      mapping.

PMID- 1383698
TI  - The detection of Mycobacterium tuberculosis in uncultured clinical specimens
      using the polymerase chain reaction and a non-radioactive DNA probe.
AB  - A Sal I-Hin dIII restriction fragment from Mycobacterium tuberculosis was found
      to hybridize specifically with genomic DNA from M. tuberculosis. Primers were
      designed from the sequence of this fragment and used to amplify uniquely M.
      tuberculosis-group DNA in a polymerase chain reaction. It is suggested that a
      combination of these primers and an acetylaminofluorene-labelled probe will prove
      to be a useful tool for the early diagnosis of tuberculous infections.

PMID- 1383697
TI  - Mapping of antibody binding epitopes of a recombinant Poa p IX allergen.
AB  - Antibody binding epitopes of a recombinant Poa p IX allergen were delineated
      using recombinant DNA and solid-phase peptide synthesis procedures. The full
      length cDNA clone KBG60 and its four overlapping recombinant fragments, KBG60.1,
      KBG60.2, KBG8.3 and KBG10 which spanned the entire molecule were synthesized in
      E. coli with aid of the plasmid expression vector, pWR590.1. The antigenic and
      allergenic sites of these recombinant proteins were analyzed by ELISA using human
      IgE and murine IgG antibodies. It was thus demonstrated that although the
      epitopes were found on all the fragments tested, the majority of these were
      located on a C-terminal fragment, rKBG8.3. Furthermore, synthetic peptides were
      also employed to identify the epitopes of rKBG60 protein. The use of antisera
      raised against native KBG pollen extract and the recombinant KBG8.3 protein to
      scan a total of 56 overlapping deca-penta peptides, covering the entire rKBG60
      protein, revealed that 10 positive peptides involved in the antibody-binding
      site(s). Taken together, the results of these studies indicate that rKBG60
      protein possesses at least 10 antibody binding epitopes.

PMID- 1383699
TI  - [Transformation of pathogenic pseudomonas by plasmid DNA].
AB  - The possibility has been shown of the genetical transformation of Pseudomonas
      mallei strains by the purified DNA of the plasmids RSF1010, pES154, pBS222 and
      pBR325. The frequency of transformation varied from 1.2 x 10(1) to 2.0 x 10(2)
      depending on the plasmid DNA and transformation technique used in the
      experiments. Pseudomonas pseudomallei cells could not be transformed by the
      methods described in the paper.

PMID- 1383700
TI  - Analysis of X-ray-induced HPRT mutations in CHO cells: insertion and deletions.
AB  - Molecular alterations were examined in the hypoxanthine guanine
      phosphoribosyltransferase (hprt) gene of 41 independent X-ray-induced thioguanine
      resistant (TGR) Chinese hamster ovary (CHO) cell clones. Rapid screening of the
      clones by multiplex polymerase chain reaction (PCR) for the presence or absence
      of exons revealed that the causes of the mutant phenotype were total gene
      deletion (26/41), partial gene deletion (4/41), and an insertion (1/41). No
      alterations of exon number or sizes were apparent in 10 of the mutants. Southern
      blot analysis confirmed the deletion data and revealed an additional class of
      mutants that had a gene disruption but retained all hprt exons (2/41). Therefore,
      at least 80% of the ionizing radiation-induced mutations were due to mechanisms
      involving DNA breakage and rejoining. The distribution of deletion sizes suggests
      that the two DNA breaks required for a deletion are not independent events. A
      possible mechanism is presented. In addition, the DNA sequence of the insertion
      mutation was determined. The insertion (229 bp) is coupled with a deletion (31
      bp). An imperfect inverted repeat with flanking hprt DNA was identified and may
      be involved in the insertion event.

PMID- 1383701
TI  - Xenobiotic-metabolizing enzymes and benzo[a]pyrene metabolism in the
      benzo[a]pyrene-sensitive mutant strain of Drosophila simulans.
AB  - Basal levels of aryl hydrocarbon hydroxylase, epoxide hydrolase and glutathione S
      transferase enzyme activities, cytochrome P-450 content and inducibility of
      enzymes with phenobarbital were found to be similar in the microsomes of D.
      simulans mutant strain 364yv, which is sensitive to the toxic and mutagenic
      effects of benzo[a]pyrene (BP), and of the wild resistant Turku strain. In
      contrast, increases in the rate of BP turnover per molecule of cytochrome P-450,
      intensity of the hemoprotein band with apparent molecular weight 56,000 and the
      yield of BP 7,8-dihydrodiol and 9,10-dihydrodiol occurred only in microsomes of
      BP-pretreated 364yv flies but not of Turku ones. It is likely that BP induces an
      aberrant form of cytochrome P-450 in 364yv flies with a rare mutation in one of
      the P-450 regulating genes.

PMID- 1383702
TI  - Natural antioxidants as inhibitors of oxygen species induced mutagenicity.
AB  - A ternary antioxidant vitamin mix consisting of ascorbic acid, alpha-tocopherol
      and lecithin as well as a rosemary extract with carnosic acid and carnosol as the
      two major active ingredients were shown to exhibit strong antimutagenic effects
      in Ames tester strain TA102. This strain has been shown to be highly sensitive to
      reactive oxygen species. Mutagenicity was induced by the generation of oxygen
      radicals by tert-butyl-hydroperoxide (tBOOH) or hydrogen peroxide (H2O2);
      therefore, the antimutagenic property of the above substances was attributed to
      their antioxidant properties. In the case of the vitamin mix, ascorbic acid was
      held responsible for this inhibitory property, whereas for the rosemary extract
      carnosic acid was identified as the antimutagenic agent. Since oxygen radicals
      are known to be involved in the multiprocess of carcinogenicity, it is concluded
      that these antioxidants might exhibit anticarcinogenic properties.

PMID- 1383703
TI  - Mechanism of antimutagenicity of wheat sprout extracts.
AB  - In this paper we have demonstrated that wheat sprout extract, which has been
      shown to be antimutagenic towards benzo[a]pyrene (BP), reduced formation of BP
      metabolites by hepatic microsomes of either benzo[a]pyrene- or phenobarbital
      treated rats as analyzed in high-pressure liquid chromatography (HPLC). Comparing
      the time dependence of profiles and values of BP metabolites, formed in
      experiments in which the same dose of wheat sprout extract was added to the
      incubation medium, it has been observed that the later this extract was added the
      higher the percent of BP that was metabolized. In a bacterial test (cytochrome
      P450 induction assay) high inhibition of mutagenic activity of cyclophosphamide
      and ethidium bromide, in the presence of wheat sprout extract, reflected
      decreased levels of cytochromes P4502B1 and P4501A1 respectively. Decreased
      levels of both cytochromes P4501A1 and P4502B1 were also observed in either wheat
      sprout extract- or wheat sprout extract plus benzo[a]pyrene-treated rats. In all
      of these studies it has been observed that wheat sprout extract displays much
      more affinity for cytochrome P4501A1 than for the P4502B1 form. On the other hand
      the wheat sprout extract had higher affinity for carcinogen binding protein (4S
      protein) than for the aryl hydrocarbon receptor. The strong inhibition of BP
      mutagenicity and BP metabolism with non-chlorophyllic wheat sprout extract
      suggests that chlorophyll is not the main compound responsible for the
      antimutagenic activity of wheat sprout extract. The similar chromatographic
      behavior of both the main inhibitory fraction, obtained from wheat sprout
      extract, and two pure glycosides of apigenin--shaftoside, purified from wheat
      sprout extract and synthetic swertisine--suggests that antimutagenic compound(s)
      contained in the wheat sprout extract belong(s) to this family of flavonoids.

PMID- 1383704
TI  - Enhancement of the mutagenicity of polyphenols by chlorination and nitrosation in
      Salmonella typhimurium.
AB  - The hydrolytic products of lignins, humic acids and industrial waste including
      hydroquinone, catechol, resorcinol, pyrogallol and 1,2,4-benzenetriol are widely
      distributed in water sources. These polyphenols can interact with chlorine or
      nitrite to yield new derivatives. Generally, these new products possess more
      mutagenic potential than their original compounds. Furthermore, the mutagenicity
      of these polyphenols and their derivatives can be dramatically reduced by rodent
      liver microsomal enzymes (S9). The mutagenicity of polyphenols is in this order:
      hydroquinone greater than 1,2,4-benzenetriol greater than pyrogallol, while
      catechol, resorcinol and phloroglucinol are non-mutagenic. The ultimate product
      of chlorination or nitrosation of hydroquinone has been identified to be p
      benzoquinone. The formation of active oxygen species including superoxide anion
      and hydrogen peroxide by polyphenols has been demonstrated and this may
      contribute partly to the molecular mechanisms of polyphenol mutagenicity.

PMID- 1383705
TI  - Radioprotection by caffeine pre- and post-treatment in the bone marrow
      chromosomes of mice given whole-body gamma-irradiation.
AB  - The effect of caffeine given as pre- and post-treatment in mice exposed to whole
      body gamma-irradiation (1.5 Gy 60Co gamma-rays) was studied. The pre-treatment
      was either acute or chronic. The acute dose (5 mg/kg and 15 mg/kg body weight)
      was in the form of an injection given intraperitoneally, 30 min before
      irradiation. The chronic administration was in the form of caffeine solution
      (4.208 x 10(-3) M and 7.72 x 10(-4) M) contained in the drinking water that mice
      had had ad libitum access to instead of plain drinking water for 5 weeks prior to
      radiation exposure. The acute pre-treatment with caffeine reduced the radiation
      induced frequency of chromosomal aberrations discernibly, whereas the chronic pre
      treatment afforded a much more significant degree of radioprotection. The
      caffeine post-treatment (5 mg/kg and 15 mg  body weight) was given in the form of
      an intraperitoneal injection to the mice immediately following whole-body gamma
      irradiation. It is noted that both post-treatment concentrations of caffeine also
      significantly reduced the frequency of chromosomal aberrations induced by gamma
      rays. These data are briefly discussed in terms of possible mechanistic
      considerations.

PMID- 1383706
TI  - Mutagenic activation of aflatoxin B1 by pulmonary, renal, and hepatic cytochrome
      P450s from rats.
AB  - The genotoxic and mutagenic activation of aflatoxin B1 (AFB1) by hepatic, renal,
      and pulmonary microsomes and purified cytochrome P450s was investigated in
      Salmonella typhimurium TA1535/pSK1002 cells in which an umu response shows DNA
      damage. The activity of the hepatic microsomes was greatest. Pulmonary microsomes
      had moderate activity and renal microsomes had low activity. P450 2C11, 2B1, 3A2,
      4A2, 4B1, K-2, and K-4 were assayed in a reconstituted system with
      dilauroylphosphatidylcholine (DLPC). P450 2C11 (a major hepatic cytochrome P450
      in male rats) had high activity. P450 2B1 (a major form as well as P450 4B1 in
      pulmonary microsomes) and K-2 (a minor form in renal microsomes) had moderate
      activity. P450 4A2 (a major form in renal microsomes), P450 K-4 (a renal form),
      and P450 4B1 had low activity. P450 3A2 did not have high activity in these
      conditions but it had high activity toward AFB1 in a modified reconstituted
      system with a lipid mixture and sodium cholate instead of DLPC only. The
      activities of other forms were not enhanced by the modification of reconstituted
      system. Anti-P450 2C11 or 3A2 antibodies inhibited the bioactivation of AFB1 by
      hepatic microsomes to 50%. These results suggest that the greater ability of
      hepatic microsomes as compared with pulmonary and renal microsomes to metabolize
      AFB1 to mutagenic products is a function of the relative proportions of the
      highly active cytochrome P450s, P450 2C11 and 3A2, in the liver.

PMID- 1383707
TI  - Radioprotective action of glycerol and cysteamine on inactivation and mutagenesis
      in Salmonella tester strains after gamma- and heavy ion irradiation.
AB  - Inactivation and mutagenesis were studied in Salmonella tester strains after
      gamma-irradiation and after heavy ion irradiation in the presence of glycerol and
      cysteamine. Ions from deuteron to carbon with residual energies of 2-9 MeV/n were
      used. Cell sensitivity slightly increased with LET before decreasing. In the
      presence of glycerol the maximum was shifted to higher values of LET. The
      radioprotective effect of glycerol for cell killing diminished gradually with
      increasing LET from 2.0 for gamma-radiation to 1.1 for carbon ions. Mutagenic
      effectiveness increased slightly for deuterium and helium ions. The protective
      effect of glycerol decreased with LET but could still be detected for helium
      ions. The radioprotective effect of cysteamine on mutagenesis was found to be
      very small in the case of gamma-radiation for the three strains examined.

PMID- 1383708
TI  - Activation of promutagens by porphyrinic biomimetic systems.
AB  - Biomimetic oxidative systems using tetraarylporphyrins, which can bind various
      metals, and exogenous oxygen donors have been extensively studied as models of
      the natural heme prosthetic group. Those systems were shown to catalyze
      oxidations in a manner consistent with cytochromes P-450 and usefully contributed
      to an understanding of the mechanisms of the cytochromes P-450-dependent
      reactions when using oxygen donors. The usage of those systems in mutagenicity
      studies showed that some promutagens could be activated to proximate mutagens. In
      the present work we report on the activation of benzo[a]pyrene, 3
      methylcholanthrene, 7,12-dimethylbenz[a]anthracene; 2-aminofluorene, 2
      acetylaminofluorene and the heterocyclic amine 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ) to Ames assay mutagens using tetraphenylporphinatoiron(III)
      chloride and various oxygen donors, namely iodosylbenzene, cumene hydroperoxide,
      tert-butylhydroperoxide and H2O2. Our results demonstrate that IQ could be
      activated using any of the oxygen donors. However, a pattern of specificity for
      the oxygen donor could be identified. Polycyclic aromatic hydrocarbons displayed
      higher levels of mutagenicity with iodosylbenzene, whereas aromatic amines were
      preferentially activated when tert-butylhydroperoxide was used. For the
      heterocyclic amine IQ the higher responses were obtained using cumene
      hydroperoxide. The putative non-carcinogen pyrene and the controversial
      carcinogen quercetin were not activated irrespective of the oxygen donor used.

PMID- 1383709
TI  - Anticlastogenic effects of a polyvitamin product, 'Pharmavit', on gamma-ray
      induction of somatic and germ cell chromosome aberrations in the mouse.
AB  - The polyvitamin product 'Pharmavit' (Pv), comprising vitamins A, D2, B1, B2, B6,
      C, E, nicotinamide, and calcium pantothene, was tested for anticlastogenic
      properties against gamma-rays in mice. Pretreatment with Pv consisted of daily
      administration by gavage for 30 days at dose levels corresponding to clinical
      recommendations for an adult human, as recalculated in terms of mg/kg. Findings
      indicated a reduction of chromosome aberrations in bone marrow cells from mice
      exposed to 3.0 Gy 137Cs gamma-rays; the reduction concerned predominantly
      fragments of the chromatid type. Furthermore, a reduction factor of 1.6 was
      obtained for the frequency of reciprocal translocations induced by spermatogonial
      irradiation in mice exposed to 4.0 Gy gamma-rays. Pretreatment with vitamin C
      alone, at the dose present in Pv, proved nearly ineffective in protecting from
      chromosome aberrations in bone marrow cells. Pharmavit is believed to be a
      promising agent for application to human populations exposed to the carcinogenic
      and genetic hazards of ionizing radiation.

PMID- 1383710
TI  - Enhancement and reduction by methylated oxypurines of the frequencies of
      chromatid aberrations induced by camptothecin in root-tip cells of Vicia faba.
AB  - In root-tip cells of Vicia faba the frequencies of chromatid aberrations induced
      by 3-h treatments with 0.05 microM camptothecin were strongly modified when the
      treatments were carried out in the presence of caffeine at concentrations above 1
      mM. Depending on the concentration of caffeine, the clastogenic effect of
      camptothecin was either enhanced or reduced. At concentrations between 1 and 6
      mM, caffeine increased the camptothecin-induced chromosome damage, the strongest
      enhancement being obtained at 5 mM. A reduction of the chromosome damage was
      apparent at caffeine concentrations above 10 mM, and in the presence of 20 mM
      caffeine the clastogenic effect of camptothecin was almost completely suppressed.
      When present during the camptothecin treatment, theophylline, 8-chlorocaffeine
      and 1,3,7,9-tetramethyluric acid influenced the induced chromosome damage in a
      similar way as caffeine, although with varying efficiency. If the concentrations
      required to produce the two types of modifying effect are used as a criterion, 8
      chlorocaffeine was the most effective and 1,3,7,9-tetramethyluric acid the least,
      whereas caffeine and theophylline were about equally effective.

PMID- 1383711
TI  - Effect of vitamin A dietary intake on in vitro and in vivo activation of
      aflatoxin B1.
AB  - The mechanism by which vitamin A prevents or delays in chemical carcinogenesis
      remains unclear. In the present study, we assess the suggestive role of vitamin A
      in the initiation phase of carcinogenesis. We have conducted a dose-effect
      relationship between vitamin A dietary intake and aflatoxin B1 (AFB1)
      genotoxicity measured both in vitro and in vivo. Thus AFB1-induced mutagenesis in
      Salmonella typhimurium TA98 was investigated and compared to AFB1-induced single
      strand breaks (SSBs) in DNA of rat hepatocytes. Rats were fed ad libitum with
      diet containing 0, 5, 50 or 500 IU of retinyl palmitate for 8 weeks. The AFB1
      treated rats were injected i.p. with 1 mg/kg body weight. In the Ames test
      conditions TA98 back-reversion was negatively correlated with the log of vitamin
      A concentration in liver S9 fractions from experimental groups. However, the
      activities of metabolizing enzymes which specifically activate or deactivate AFB1
      were found to be significantly decreased in vitamin A-deficient animals and
      weakly modified in vitamin A-supplemented animals. For in vivo experiments, the
      DNA elution rate of both AFB1-treated and untreated rats was increased in vitamin
      A deficiency condition (+79% and +17% respectively) and was reduced with the
      higher vitamin A dietary level (-44% and -53% respectively). DNA damage measured
      in vivo showed a significant positive correlation with mutagenic activity
      measured in the Ames test. These results confirm that the vitamin A status of
      animals can influence AFB1 genotoxic activity in vitro and indicate that this
      phenomenon also occurs in vivo. Thus a similar mechanism may be considered for
      the protective action of vitamin A both in vitro and in vivo. However, this
      mechanism is unlikely to involve modulation of the microsomal enzyme system
      responsible for AFB1 metabolism. Therefore a protective mechanism at the
      cytosolic or nuclear levels may be suggested.

PMID- 1383712
TI  - Inhibition of the metabolism of mutagens occurring in food by arachidonic acid.
AB  - Hepatic microsomal fractions (microsomes) were prepared from male Sprague-Dawley
      rats. The effect of arachidonic acid on the conversion of the heterocyclic
      aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to its genotoxic
      metabolites was investigated using a modified bacterial mutation assay
      (indicator: Salmonella typhimurium TA98). Arachidonic acid inhibited the
      mutagenicity of IQ without effect on the uptake of the active metabolites and/or
      on the DNA-repair processes within the bacterial cell. The activation of 2-amino
      3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) and aflatoxin B1 (AFB1) was also inhibited by
      this polyunsaturated fatty acid.

PMID- 1383714
TI  - A contribution to the study of the structure-mutagenicity relationship for alpha
      dicarbonyl compounds using the Ames test.
AB  - The mutagenicity of a series of nine alpha-dicarbonyl compounds against S.
      typhimurium strain TA100 was studied using the Ames test (standard plate
      incorporation assay) without preincubation. Acetylbenzoyl, sodium glyoxylate and
      camphorquinone were not mutagenic. The following sequence of activities (in
      revertants per mumol of free dicarbonyl added) was obtained: glyoxal greater than
      methylglyoxal greater than phenylglyoxal much greater than 1,2-cyclohexanedione
      much greater than diacetyl greater than 3,4-hexanedione. These compounds can be
      grouped in three series: aldehydes, ketones and enolizable ketones (1,2
      cyclohexanedione). In each of the two first groups the mutagenic activity
      decreases when the size of the substituent increases. No relation was found
      between the mutagenicity and the molecular electronic and/or resonance
      parameters. The low or non-existent activity of some of the chemicals studied is
      discussed. A relation between the mutagenic activities and the polarographic
      reduction potentials and, consequently, the structures of the mutagens was found.

PMID- 1383713
TI  - The distribution of UV damage in the lacI gene of Escherichia coli: correlation
      with mutation spectrum.
AB  - We have determined the UV (254 nm) damage distribution in the transcribed and non
      transcribed strands of the i-d region of the Escherichia coli lacI gene. The
      locations of replication blocking lesions were revealed as termination sites of
      T7 DNA polymerase and/or T4 DNA polymerase 3'-5' exonuclease. Termination
      products, i.e. both cyclobutane pyrimidine dimers and 6-4 photoproducts, were
      resolved and analysed on an automated DNA sequencer. These two major
      photoproducts are not randomly distributed along the gene, but occur in clusters,
      in longer runs of pyrimidines. We also have compared the UV damage distribution
      with the previously reported UV-induced base substitutions in the same region.
      Mutational hotspots, in both repair-deficient and repair-proficient strains of E.
      coli, are all located in stretches of pyrimidines, and thus correlate well with
      the distribution of photolesions. One mutational hotspot in the wild-type strain
      may reflect the high frequency of closely opposed lesions. To explain the other
      mutational hotspots, we propose that the repair of UV lesions is impaired due to
      the local conformation of the DNA, which might deviate from the B-form. This
      hypothesis is supported by the excess of mutational hotspots in pyrimidine runs
      in the Uvr+ strain compared to Uvr-. Runs of pyrimidines thus represent both
      damage- and mutation-prone sequences following UV treatment.

PMID- 1383715
TI  - Effects of sodium selenite and caffeine on mutagenesis induced by N-methyl-N
      nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and aflatoxin B1 in S.
      typhimurium.
AB  - Pre-treatment, co-treatment, and post-treatment procedures were comparatively
      used in order to assess the modulation of mutagenicity in S. typhimurium his-
      strains. Pre-treatment of bacteria with sodium selenite had no effect on sodium
      azide mutagenicity. Irrespective of the procedure used neither selenite nor
      caffeine had any influence on the S9-mediated mutagenicity of aflatoxin B1. In
      contrast, the mutagenicity of N-methyl-N-nitrosourea (MNU) and N-methyl-N'-nitro
      N- nitrosoguanidine (MNNG) was variably affected, depending on the sequence of
      exposures of target bacterial cells to mutagens and modulators. In particular,
      pre-treatment of bacteria with either selenite or caffeine or their combination
      generally resulted in a potentiation of MNU and MNNG mutagenicity. However, co
      incubation of these alkylating agents and test modulators with bacterial cells
      yielded an evident inhibition of mutagenicity, the methylxanthine being more
      effective in this case. Caffeine exhibited an an antimutagenic effect towards MNU
      also when assayed in a post-treatment procedure. Thus, in dependence on the test
      conditions, selenite and caffeine could act in the same mutagenicity assay as co
      mutagens, antimutagens or agents without effect on mutagenesis. These opposite
      trends reflect the complexity of the mechanisms of action of both mutagens and
      modulators tested, and underscore the variable outcome of their interactions,
      also depending on topological and chronological factors. The data reported
      emphasize the need for a multiple methodological approach in studies
      investigating the modulation of mutagenicity.

PMID- 1383717
TI  - Environmental monitoring for genotoxicity with plant systems.

PMID- 1383716
TI  - Nalidixic acid-resistant V79 cells with reduced DNA topoisomerase II activity and
      amplification prone phenotype.
AB  - Spontaneously nalidixic acid-resistant lines (NAr lines) were selected from a V79
      Chinese hamster cell line and phenotypically characterized. NAr lines showed an
      increased doubling time, a higher number of spontaneous SCE, and more
      interestingly, decreased DNA topoisomerase II activity. These lines were also
      cross-resistant to the eukaryotic topoisomerase II inhibitors etoposide and
      adriamycin, but showed the same level of sensitivity as the parental line to the
      DNA topoisomerase I inhibitor camptothecin. NAr lines were cross-resistant to
      other drugs, such as PALA, MTX and MPA, resistance to which has been shown to
      arise by amplification of the target genes. This last feature, together with
      enhanced cross-resistance to PALA and MTX when employed simultaneously, suggests
      that NAr lines have an 'amplification prone' phenotype. From these results the
      decreased activity of topoisomerase II seems to be involved in the generation of
      amplified sequences possibly by affecting recombinational events underlying gene
      amplification.

PMID- 1383718
TI  - Tradescantia stamen-hair mutation bioassay on the mutagenicity of radioisotope
      contaminated air following the Chernobyl nuclear accident and one year later.
AB  - This paper presents results of the research on the mutagenic effect of ambient
      air in the Cracow area. Initial studies were conducted in May 1986, following the
      Chernobyl accident. Other studies were performed at various sites within the
      Cracow area in the Spring of 1987. Counts were made of stunted hairs and pink
      cells in the stamen hairs of Tradescantia clone 4430. Mutations scored from the
      11th day after the beginning of exposure were used as a measure of the mutagenic
      effect. The mean mutation frequencies measured in 1986 and 1987 were 0.43 and
      0.21 per 100 hairs respectively. The time-dependent development of mutation
      frequencies observed after the Chernobyl accident showed a correlation with the
      time-dependent development of total radioactivities measured in the air at that
      time. The results obtained in 1987 showed on average a significant decrease of
      ambient air mutagenicity. Still, the variation of mutation rates observed during
      the investigated period at different sites in the Cracow area was rather high
      (0.09-0.38 mut/100 hairs). Only the highest frequencies observed in the Spring of
      1987 were comparable to the level detected after the Chernobyl accident.

PMID- 1383719
TI  - Tradescantia stamen-hair system as an excellent botanical tester of mutagenicity:
      its responses to ionizing radiations and chemical mutagens, and some synergistic
      effects found.
AB  - The stamen-hair system of Tradescantia heterozygous for flower color (blue/pink,
      the pink color being recessive) is an excellent botanical tester of mutagenicity.
      It is especially useful for detection of the genetic effects of both ionizing
      radiations and chemical mutagens at the low levels of exposure to which the human
      population may actually be exposed. This system exhibits a high accuracy in
      laboratory experiments, and is also applicable for in situ monitoring in the
      environment. The use of the Tradescantia stamen-hair system is inexpensive and
      requires only a short training time. Simplified scoring methods which endorse a
      high statistical accuracy have newly been developed to score larger samples of
      pink somatic mutations. In the present paper, the most widely used clones,
      methods for their cultivation, and use in a variety of experiments with
      radiations and chemical mutagens are also reviewed.

PMID- 1383720
TI  - Synergistic effect between tannic acid and X-rays detected by the Tradescantia
      micronucleus assay.
AB  - Tannic acid (TA), a complex mixture of polyphenolics, exhibited synergism with 4
      nitroquinoline 1-oxide (4-NQO), methyl methanesulfonate (MMS) and cis-platinum
      (cis-DDP) in a recent study on w/w+ somatic mutation in the eye pigment of
      Drosophila, although several studies indicated that tannic acid is an antimutagen
      in cultured mammalian cells. The goal of this study was to determine the
      genotoxicity of tannic acid alone and its possible synergistic effect with X-rays
      using the Tradescantia-micronucleus (Trad-MCN) bioassay. Plant cuttings were
      irradiated with 35 R of X-rays (80 kV, 5 mA) and followed by a series of
      increasing dosages (0.1, 0.5, 0.75, 1.0, 1.25, 1.50 mM) of TA treatment (24 h)
      and in some cases TA treatment was followed by X-irradiation. Inflorescences were
      fixed after a 24-h recovery period and slides were prepared for scoring MCN
      frequencies. Four series of experiments were conducted and the results of Trad
      MCN tests on X-rays alone yielded an average of 47.5 MCN/100 tetrads (SE = 6.08),
      and 1.0 mM TA alone yielded an average of 8.95 MCN/100 tetrads (SE = 0.1), while
      the combined treatments (35 R X-rays plus 1.0 mM TA) yielded an average of 126.95
      MCM/100 tetrads (SE = 13.69). The MCN frequency of the negative control was
      around 4.6 MCN/100 tetrads (SE = 0.75). This kind of synergism was exhibited
      through all the increasing dosages around 1.0 mM or higher. The synergistic
      effect of these two agents remained at the same level when TA was followed by X
      irradiation. When a 12-h repairing period was allowed after X-irradiation in the
      combined treatment, the MCN frequency was similar to that of the X-ray treatment
      alone. The synergistic effect in the cases where the TA exposure was given
      immediately after X-irradiation could be attributed to the inhibitory action of
      TA on the DNA repair process.

PMID- 1383721
TI  - Proficiency of the Tradescantia-micronucleus image analysis system for scoring
      micronucleus frequencies and data analysis.
AB  - The Tradescantia-micronucleus (Trad-MCN) bioassay is an efficient short-term test
      for genotoxicity of pollutants. In order to increase the efficiency and to
      standardize the micronucleus (MCN) scoring process, an automated scoring system
      was developed using the principle of image analysis in computer science. This
      assemblage is called the Tradescantia-micronucleus image analysis (Trad-MCNIA)
      system. The MCN frequencies scored by this system were compared with those scored
      by human observation for its proficiency. A set of low MCN frequency (around 5
      MCN/100 tetrads) slides prepared from a control group, a set of medium MCN
      frequency (around 20 MCN/100 tetrads) slides prepared from sodium azide treated
      plant cuttings and a set of high MCN frequency (around 50 MCN/100 tetrads) slides
      prepared from X-ray treated materials were used for this study. In the low MCN
      frequency slides, the Trad-MCNIA system scored about the same value as human
      observation. In the medium and high frequency slides, MCN frequencies scored by
      the system were lower than those scored by human observers. This discrepancy was
      corrected by increasing the power of the objective of the microscope in the
      system. The MCN frequencies scored by the system attained 90% congruity with
      those scored by human observers after the correction. The scoring speed of the
      system was about 3.5 times as fast as that by human observers, and the data could
      be statistically analyzed immediately after the data scores were recorded.
      Further improvements can be made by upgrading the video camera and the computer
      speed.

PMID- 1383722
TI  - Tradescantia-micronucleus (Trad-MCN) bioassay on clastogenicity of wastewater and
      in situ monitoring.
AB  - The Tradescantia-micronucleus (Trad-MCN) bioassay was used to determine the
      clastogenicity of wastewater samples collected from the Arena canal which
      contains effluent from the industrial district Benito Juarez of the city of
      Queretaro, Mexico. Fifteen wastewater samples which were collected, in most
      cases, at bi-weekly intervals beginning in September 1986 through February 1988,
      after a 3-fold dilution were used to treat Tradescantia plant cuttings. The
      clastogenicity expressed in terms of micronucleus frequencies of treated groups
      (30 h of treatment without recovery time) was significantly (0.01) higher than
      that of the tapwater control groups. The Trad-MCN bioassay was also used for in
      situ monitoring of air pollutants for the clastogenicity at 3 sites near the
      industrial and residential areas (Flores Magon, Conalep and Bellas Artes) of the
      city of Queretaro. Fourteen monitoring trips were made to each of the 3 sites at
      monthly intervals beginning in May 1988 through June 1990. Seasonal variation of
      micronucleus frequencies was exhibited with the peak clastogenicities shown in
      May and June 1988, June 1989 and April 1990 at the three sites. Micronucleus
      frequencies of all the exposed groups at the Conalep site, a predominantly
      industrial area, were markedly higher than that of the laboratory control groups
      throughout the 2-year period.

PMID- 1383724
TI  - Application of the Tradescantia micronucleus assay for the genetic evaluation of
      chemical mixtures in soil and aqueous media.
AB  - Genotoxic evaluations of arsenic trioxide, dieldrin, lead tetraacetate and their
      nine binary and one tertiary mixtures were performed using the Tradescantia
      micronucleus (Trad-MN) assay. The chemicals or their mixtures were either (1)
      mixed into soil, and chemical exposure to the target cells was through the roots
      of intact plants grown in the soil or (2) through plant cuttings in which the
      inflorescences received treatment by absorption through stem of an aqueous
      solution of the test chemicals. All three chemicals yielded clastogenic responses
      when tested in soil medium and only two of these i.e. arsenic trioxide and
      dieldrin were positive when plant cuttings were exposed to the test chemicals in
      the aqueous medium. The clastogenicity of the chemical mixtures was modified by
      the ratio of the individual chemical in a particular mixture and also by the
      medium in which these mixtures were tested.

PMID- 1383723
TI  - The use of Tradescantia and Vicia faba bioassays for the in situ detection of
      mutagens in an aquatic environment.
AB  - Tests have shown plant bioassays to be excellent for mutagenicity studies. Most
      studies with plant bioassays, however, have been carried out either in the
      laboratory, or if, in situ, as monitors of atmospheric contaminants. The primary
      purpose of this study was to assess the utility of in situ plant mutagenicity
      bioassays in monitoring water contaminants. The assay systems tested were the
      Tradescantia stamen hair and micronucleus assays for the detection of gene
      mutations and chromosomal aberrations respectively, and the Vicia faba bioassay
      system which detects chromosomal aberrations in root tips. The assays were used
      to test the effluent from a pulp and paper mill located on the north shore of
      Lake Superior. Assays were performed in a creek containing raw effluent and in
      the bay of Lake Superior into which the creek emptied. All in situ treatments
      were carried out for 24 h. The effluent from the creek was heavy with pulp and
      debris which coated the plant cuttings and the Vicia faba seedlings and may have
      restricted the uptake from the effluent. In the creek, at test sites 11.5 km from
      the source, the effluent was toxic to the Vicia faba roots as evidenced by a
      reduction in the mitotic index. The data for the Tradescantia stamen hair assay
      in the creek were equivocal. The cuttings from the creek test sites and the air
      and water control sites appeared to have undergone a physiological delay. Within
      a day or two after the return to the laboratory, that is 6-8 days after testing,
      flowering almost ceased and did not fully resume until about day 35. This
      reduction in flowering was particularly severe with the cuttings from the
      effluent and air control sites, making it very difficult to interpret the
      results. In contrast, the Tradescantia micronucleus and Vicia faba chromosomal
      aberration data were unequivocal; each produced positive responses at both test
      sites relative to the air and water controls. The results obtained for the bay
      sites with all 3 assays were in agreement. In that section of the bay visibly
      contaminated by the creek effluent, increases in stamen hair mutants,
      micronuclei, and chromosome aberrations were measured. In general, there was a
      considerable reduction in the number of mutant events observed for the water
      samples brought back from the test sites and tested in the laboratory.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1383726
TI  - Application of a wheat seedling assay for detecting aneuploidy induced by N-ethyl
      N-nitrosourea and 4-nitroquinoline-1-oxide.
AB  - N-Ethyl-N-nitrosourea (ENU) and 4-nitroquinoline-1-oxide (4NQO) were evaluated in
      the allohexapolyploid wheat seedling assay developed by Redei and Sandhu (1988),
      for its ability to induce aneuploidy and/or small chromosome deletions. The wheat
      strain used (Neatby's virescent) is homozygous for a pair of recessive alleles
      (v1) present on chromosome 3B and produces virescent seedlings grown at
      temperatures below 26 degrees C. When the developing embryos are treated with a
      test chemical, loss of chromosome 3B or its segment bearing the v1 allele in a
      progenitor cell produces a green sector in the leaf, whereas a gain of this
      chromosome induces a white sector. ENU and 4NQO induced dose-dependent increases
      in the frequency of leaf sectors at concentrations ranging from 0.128 to 1.280 mM
      and 0.052 to 0.263 mM, respectively. The assay is very simple and can be employed
      for evaluating the genetic potential of chemicals in a laboratory as well as for
      in situ hazards assessment under natural environmental conditions.

PMID- 1383725
TI  - Synergistic and antagonistic effects on genotoxicity of chemicals commonly found
      in hazardous waste sites.
AB  - Synergistic and antagonistic effects on genotoxicity of mixtures of four
      chemicals; i.e., lead tetraacetate (LTA), arsenic trioxide (ATO), dieldrin (DED),
      and tetrachloroethylene (TCE), were evaluated by the Tradescantia-micronucleus
      (Trad-MCN) assay. The chemicals were mixed in ratios of 1:1, 1:2 and 2:1 for
      mixtures of two chemicals and 1:1:1 each for three chemicals. The concentration
      of stock solution of these chemicals was around the minimum effective dose (MED)
      or below the MED for these chemicals as reported by Sandhu et al. (1989).
      Treatments were applied to plant cuttings by hydroponic uptake of the mixed
      solutions through the stems of the plant for 30 h followed by fixation of the
      flower buds in aceto-alcohol (1:3 ratio) without a recovery period. Microslides
      were prepared for scoring MCN frequencies. Results of two series of repeated
      experiments indicated that all mixtures of LTA/ATO exhibited antagonistic
      effects. On the other hand, all mixtures of TCE and DED exhibited synergistic
      effect. These data indicate that for evaluating biological hazards at chemical
      waste sites, it is prudent to evaluate the genotoxicity of complex chemical
      mixtures as these exist in nature because the biological effects based on
      evaluating individual chemicals may not be true predictors of the interactive
      effects of the pollutants.

PMID- 1383727
TI  - The load of genetic and partially genetic disease in man. IV. Severe visual
      handicaps and profound childhood deafness in Hungarian school-age children.
AB  - In Hungary, the school-age prevalences of severe visual handicaps and of profound
      childhood deafness have been estimated to be about 6/10(4) and 10/10(4),
      respectively. Most of these conditions have onset at birth or in early childhood
      and are aetiologically heterogeneous. Severe visual handicaps are grouped under
      11 aetiological categories, their relative contributions to the prevalence being:
      perinatal damage syndrome (20%; half of this is due to retinopathy of premature
      infants), cataracts (15%), choroidoretinal degenerations (15%), congenital
      abnormalities of the eye (15%), syndromes (10%), high myopia +/- retinal
      detachment (7%), postnatal causes (5%), nystagmus (5%), optic atrophy (4%),
      bilateral retinoblastoma (2%) and prenatal causes (2%). Overall, Mendelian
      conditions (included under many of the above) account for about 50% with
      relatively more autosomal dominant than autosomal recessive and sex-linked
      entities, and acquired causes account for about 40% of the cases studied. No
      aetiology could be assigned in 10% of the cases. For profound childhood deafness,
      the rank order of the aetiological categories is: autosomal recessive entities
      (34%), postnatal causes (22%), perinatal causes (19%), autosomal dominant
      entities (17%), prenatal causes (5%) and unknown causes (3%). Severe childhood
      visual handicaps are responsible for about 60 years of loss of life per 10(4)
      live births and about 400 years of impaired life per 10(4) live births. Genetic
      causes account for one-quarter of lost life years and three-quarters of impaired
      life years. The comparable estimates for profound childhood deafness are: about
      240 years of life loss per 10(4) live births (again, about one-quarter due to
      genetic causes) and about 640 years of impaired life per 10(4) live births (about
      one-half due to genetic causes). In all these calculations, it has been assumed
      that the average life expectancy at birth for an individual in the population is
      70 years.

PMID- 1383728
TI  - DNA base sequence changes in spontaneous and ethyl methanesulfonate-induced
      mutations of a chromosomally-integrated gene in Chinese hamster ovary cells.
AB  - A series of spontaneous and ethyl methanesulfonate-induced 6-thioguanine
      resistant mutants were isolated in the CHO-10T5 cell line. This cell line was
      constructed by the introduction of a shuttle vector containing the Escherichia
      coli gpt gene into a hypoxanthine-guanine phosphoribosyltransferase deficient
      derivative of the Chinese hamster cell line CHO-K1. Shuttle vector sequences were
      recovered from many of the mutant cell lines by the COS cell fusion technique and
      the DNA base sequence of the gpt genes was determined whenever possible. The base
      sequences were determined for gpt genes recovered from 29 spontaneous mutants. Of
      these 29 mutants, 9 have single base substitutions, 1 has a small duplication, 17
      have simple deletions, 1 has a deletion with additional bases inserted at the
      deletion site, and 1 has no change in the gpt coding sequence. Many of the
      deletions were less than 20 basepairs in length and several occurred in a region
      previously observed to be a hotspot for spontaneous deletions. The generation of
      the deletion/insertion mutation may have involved a quasi-palindromic
      intermediate. A total of 59 ethyl methansesulfonate-induced mutants were isolated
      and vector sequences were recovered from 50 mutants. All 50 mutants sequenced had
      single base substitutions and most (45) were G:C to A:T transitions. While there
      were no strong hotspots in this collection of mutations, the site distribution
      was obviously nonrandom. Many of the G:C to A:T transitions either produced a
      nonsense codon or occurred at glycine codons.

PMID- 1383729
TI  - Sister-chromatid exchange in highly purified human CD4+ and CD8+ lymphocytes.
AB  - Sister-chromatid exchange (SCE) frequencies were determined in human peripheral
      blood CD4+ and CD8+ T lymphocyte subpopulations which were rapidly and highly
      purified from pooled T lymphocytes by immunological methods. The purified
      lymphocytes were stimulated with phytohemagglutinin (PHA) for 4 days. CD4+
      lymphocytes showed significantly higher SCE frequencies than autologous CD8+
      lymphocytes when measured simultaneously after identical bromodeoxyuridine (BrdU)
      incubation times. Differences in SCE frequencies between CD4+ and CD8+
      lymphocytes were also detected when mitomycin C (MMC) was added to the cultures.
      Higher SCE frequencies in CD4+ lymphocytes were associated with lower
      proliferating rate indices (PRI) as compared to autologous CD8+ lymphocytes.
      Abnormalities in CD4+ T lymphocyte function and number in peripheral blood have
      been observed in several diseases characterized by immunological disorders. Thus,
      our data may suggest a link between some immunological disturbances and abnormal
      SCE frequencies in T lymphocyte subsets.

PMID- 1383730
TI  - Mutagenic DNA repair in Escherichia coli. XXI. A stable SOS-inducing signal
      persisting after excision repair of ultraviolet damage.
AB  - Mutations to streptomycin resistance induced by ultraviolet light in Escherichia
      coli can lose their susceptibility to photoreversing light during excision repair
      and in the absence of chromosomal replication and protein synthesis, i.e., under
      conditions where SOS induction cannot occur. Using fusions of lac with sulA and
      umuC we have shown that after excision of UV damage in the presence of
      chloramphenicol there is a persisting, relatively stable signal capable of
      inducing SOS genes when protein synthesis is subsequently permitted. The
      persisting signal is formed roughly in proportion to the square of the UV dose
      and is about 30% photoreversible. It is suggested that the persisting SOS
      inducing signal comprises a UV photoproduct (the target lesion) opposite a gap in
      the opposing DNA strand, and is formed by excision of one (the ancillary lesion)
      of a pair of closely opposed photoproducts. Calculations suggest that as few as
      two or three such configurations in a cell can lead to induction of sulA when
      protein synthesis is permitted. It is not clear whether these configurations can
      directly induce the SOS system because of their region of single-stranded DNA or
      whether the ultimate SOS-inducing signal is a more extensive single-stranded
      region formed when such configurations encounter a replication fork.
      Photoproduct/gap configurations have been previously suggested to be potentially
      mutagenic. UV-induced mutations to streptomycin resistance are mostly at A:T
      sites and are not photoreversible in fully SOS-induced bacteria in the absence of
      excision repair, indicating that they are not targeted at cyclobutane-type
      pyrimidine dimers. In SOS-induced excision-proficient bacteria there is about 39%
      photoreversibility which is rapidly lost after UV. This photoreversibility is
      attributed to many ancillary lesions being cyclobutane-type pyrimidine dimers
      which are excised leading to the exposure of target lesions on the opposing
      strand which, at these particular sites, are mostly non-photoreversible
      photoproducts.

PMID- 1383731
TI  - Effect of plasmid pKM101 in ultraviolet irradiated uvr+ and uvr- Escherichia
      coli.
AB  - The effect of plasmid pKM101 on UV irradiated excision proficient and excision
      deficient cells was investigated. The plasmid increased the survival of excision
      proficient cells while partially inhibiting thymine dimer excision. The frequency
      of mutations was almost unchanged. In excision deficient cells the effect of the
      plasmid on survival was less pronounced while cell mutability was increased. Our
      data indicate that the mucAB genes (carried by the plasmid) influence the two
      types of cells in a different way.

PMID- 1383732
TI  - Formaldehyde, glyoxal, urethane, methyl carbamate, 2,3-butanedione, 2,3
      hexanedione, ethyl acrylate, dibromoacetonitrile and 2-hydroxypropionitrile
      induce chromosome loss in Saccharomyces cerevisiae.
AB  - Induction of mitotic chromosome loss could be demonstrated for the dialdehyde
      glyoxal, the diketones 2,3-butanedione and 2,3-hexanedione, ethyl and methyl
      carbamate, ethyl acrylate, dibromoacetonitrile, 2-hydroxypropionitrile and
      formaldehyde, but only when they were combined with subacute concentrations of
      propionitrile, which is a strong inducer of chromosomal malsegregation. The same
      chemicals did not induce mitotic chromosome loss when applied in pure form.
      However, glyoxal, ethyl acrylate, dibromoacetonitrile and formaldehyde when
      applied in pure form also induced mitotic recombination. Respiratory deficiency
      was induced, in the absence of propionitrile, by these recombinogenic agents and
      also by 2,3-hexanedione and 2-hydroxypropionitrile which are not recombinogenic.

PMID- 1383733
TI  - Effects of an inhibitor and a mimic of superoxide dismutase on bleomycin
      mutagenesis in Chinese hamster ovary cells.
AB  - We have investigated the roles of reactive oxygen species (ROS) in bleomycin
      (BLM)-induced gene mutations in Chinese hamster ovary (CHO) cells using a
      superoxide dismutase (SOD) inhibitor, triethylenetetramine (TRIEN), and a SOD
      mimic, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEM-POL), to lower and
      increase intracellular 'SOD activity', respectively. Pretreatment of CHO cells
      with TRIEN (1 mM) for 1 h enhanced the mutagenic response of BLM (5-50
      micrograms/ml, 1 h treatment) in the hypoxanthine-guanine
      phosphoribosyltransferase (hprt) locus in CHO cell clone K1-BH4 (CHO/HPRT assay)
      and the xanthine-guanine phosphoribosyltransferase (gpt) gene in a CHO-K1 cell
      derivative AS52 (AS52/GPT assay). Pretreatment with TEMPOL (1 mM) for 1 h
      decreased the BLM (20-100 micrograms/ml, 1 h treatment) mutagenicity in the
      AS52/GPT assay. The mutagenic response of BLM appears to be modulated by the
      intracellular level of 'SOD activity' and hence the intracellular level of ROS.
      These data provide further evidence for the involvement of ROS in bleomycin
      mutagenesis in mammalian cells.

PMID- 1383734
TI  - Mitomycin C, 4-nitroquinoline-1-oxide and ethyl methanesulfonate induce long
      lived lesions in DNA which result in SCEs during successive cell cycles in human
      lymphocytes.
AB  - The present study was carried out in order to analyze how persistent the lesions
      in DNA are which elicit sister-chromatid exchanges (SCEs), induced by three
      different chemical agents, mitomycin C (MMC), 4-nitroquinoline-1-oxide (4NQO) and
      ethyl methanesulfonate (EMS), in proliferating human lymphocytes. Cells were
      exposed to the mutagens for 1 h just before starting bromodeoxyuridine
      substitution and SCEs were examined in third-cycle metaphases showing three-way
      differential staining, by means of our previously standardized method. The
      results show that, in spite of the fact that these three compounds have different
      modes of action, the lesions induced by all of them seem to be capable of
      persisting in DNA and eliciting SCEs for at least three successive cell cycles.

PMID- 1383735
TI  - Cell cycle effects of the DNA topoisomerase inhibitors camptothecin and m-AMSA in
      lymphoblastoid cell lines from patients with Fanconi anemia.
AB  - Patients with the autosomal recessive disorder Fanconi anemia (FA) present with
      progressive pancytopenia, skeletal abnormalities and a predisposition to
      leukemia. In addition to elevated rates of spontaneous chromosome aberrations
      occurring in cultured fibroblasts and lymphoblastoid cell lines, an increased
      susceptibility to DNA cross-linking agents and oxygen has been found. To explain
      this hypersensitivity to clastogenic agents a defective function of DNA
      topoisomerase I or II could be invoked, a suggestion which is supported by the co
      localization of the DNA topoisomerase I gene and a putative FA gene to chromosome
      20q. In order to investigate the function of DNA topoisomerases in FA, the
      sensitivity of lymphoid B-cell lines derived from FA patients and control cell
      lines to inhibitors of DNA topoisomerases I and II was compared using continuous
      bromodeoxyuridine labeling and bivariate Hoechst/ethidium bromide flow cytometry.
      Both agents inhibited cell proliferation mainly by arresting cells in the G2
      phase of the cell cycle. However, no difference was found in sensitivity towards
      both DNA topoisomerase inhibitors between control and FA cell lines.

PMID- 1383736
TI  - Persistently elevated frequency of spontaneous mutations in progeny of CHO clones
      surviving X-irradiation: association with delayed reproductive death phenotype.
AB  - Certain clonal progeny of Chinese hamster ovary (CHO) cells surviving X
      irradiation demonstrate pleomorphic changes including a persistently decreased
      cloning efficiency, a dominant phenotype we have termed delayed reproductive
      death (Chang and Little, 1991, 1992b). We now report that cells from these
      progeny clones show a persistently elevated frequency of spontaneous mutations at
      the hprt locus for up to 95-100 population doublings post-irradiation. Mutant
      fractions as high as 10(-3) were scored, more than two orders of magnitude higher
      than those observed in clonal progeny of non-irradiated cells studied in
      parallel. These results are discussed in terms of the hypothesis that radiation
      induces a type of genetic instability among some surviving cells that results in
      a heritable mutator phenotype, and that this instability may also be involved in
      the phenomenon of delayed reproductive death.

PMID- 1383737
TI  - In vitro mammalian mutagenesis as a model for genetic lesions in human cancer.
AB  - Recently in vitro assays of mutagenesis have been criticized as being poorly
      predictive of long-term in vivo rodent assays of carcinogenicity. Questions have
      also been raised concerning the relevance of rodent assays to human risk. In
      vitro assays using mammalian cells can detect most types of genetic lesions
      thought to be important in human malignant disease. Molecular and cytogenetic
      analyses of mutations induced by a variety of genotoxic compounds at the
      heterozygous thymidine kinase locus in mouse lymphoma cells indicate that this in
      vitro assay does indeed register the range of genetic lesions recently found in a
      wide variety of human tumors. The types and complexity of the induced lesions are
      reflected in mutant colony phenotype in a compound-specific fashion. These
      studies point to the use of appropriate in vitro mammalian mutagenesis assays as
      new model systems for dissecting the genetic lesions important in human
      carcinogenesis, and as a means of determining the potential for compounds to
      induce such lesions.

PMID- 1383738
TI  - Effects of progesterone and estradiol on the proliferation of phytohemagglutinin
      stimulated human lymphocytes.
AB  - In this paper we report on a study to elucidate whether the response of human
      lymphocytes to mitogenic stimulation was modified by physiological changes which
      occur during the menstrual cycle. Experiments with untreated cultures showed
      intra-individual variation to mitogen stimulation in female lymphocyte cultures,
      but a significant correlation between the menstrual cycle and the proliferation
      kinetics of lymphocytes was not found. Consequently, we performed experiments in
      which two of the hormones that regulate the menstrual cycle in women, estradiol
      and progesterone, were added to cultured human lymphocytes obtained from both men
      and women. The results indicate that both hormones at physiological
      concentrations have the capacity to modify the proliferation of PHA-stimulated
      human lymphocytes. Therefore, both hormones could play a role in the induction of
      the intra-individual variation observed in the untreated female cultures.
      However, in vivo other factors could also modify the proliferation kinetics of
      human lymphocytes preventing the demonstration of the effects of a single factor,
      such as the hormonal changes occurring during the menstrual cycle.

PMID- 1383739
TI  - An Escherichia coli plasmid-based, mutational system in which supF mutants are
      selectable: insertion elements dominate the spontaneous spectra.
AB  - A new system is described to determine the mutational spectra of mutagens and
      carcinogens in Escherichia coli; data on a limited number (142) of spontaneous
      mutants is presented. The mutational assay employs a method to select (rather
      than screen) for mutations in a supF target gene carried on a plasmid. The E.
      coli host cells (ES87) are lacI- (am26), and carry the lacZ delta M15 marker for
      alpha-complementation in beta-galactosidase. When these cells also carry a
      plasmid, such as pUB3, which contains a wild-type copy of supF and lacZ-alpha,
      the lactose operon is repressed (off). Furthermore, supF suppression of lacIam26
      results in a lactose repressor that has an uninducible, lacIS genotype, which
      makes the cells unable to grow on lactose minimal plates. In contrast,
      spontaneous or mutagen-induced supF- mutations in pUB3 prevent suppression of
      lacIam26 and result in constitutive expression of the lactose operon, which
      permits growth on lactose minimal plates. The spontaneous mutation frequency in
      the supF gene is approximately 0.7 and approximately 1.0 x 10(-6) without and
      with SOS induction, respectively. Spontaneous mutations are dominated by large
      insertions (67% in SOS-uninduced and 56% in SOS-induced cells), and their
      frequency of appearance is largely unaffected by SOS induction. These are
      identified by DNA sequencing to be Insertion Elements; IS1 dominates, but IS4,
      IS5, gamma-delta and IS10 are also obtained. Large deletions also contribute
      significantly (19% and 15% for -SOS and +SOS, respectively), where a specific
      deletion between a 10 base pair direct repeat dominates; the frequency of
      appearance of these mutations also appears to be unaffected by SOS induction. In
      contrast, SOS induction increases base pairing mutations (13% and 27% for -SOS
      and +SOS, respectively). The ES87/pUB3 system has many advantages for determining
      mutational spectra, including the fact that mutant isolation is fast and simple,
      and the determination of mutational changes is rapid because of the small size of
      supF.

PMID- 1383740
TI  - Genotoxicities of nitropyrenes and their modulation by apigenin, tannic acid,
      ellagic acid and indole-3-carbinol in the Salmonella and CHO systems.
AB  - Four naturally occurring compounds, indole-3-carbinol (I3C), apigenin (Api),
      ellagic acid (EA) and tannic acid (TA), were tested for their inhibitory effects
      against 1-nitropyrene- (1-NP) or 1,6-dinitropyrene (1,6-DNP)-induced genotoxicity
      in Salmonella tester strains and Chinese hamster ovary (CHO) cells. Api and TA
      strongly inhibited the bacterial mutagenesis induced by nitropyrenes, while I3C
      and EA had little or no effect. For example, in TA98, 0.2 mumole Api resulted in
      48% and 56% inhibition of the mutagenicity induced by 4 nmole 1-NP and 0.035
      nmole 1,6-DNP, respectively. With an equal dose, TA caused 46% and 50% reduction
      of the mutagenicity induced by 1-NP and 1,6-DNP, respectively. As expected, a
      good correlation was observed between the antimutagenicity of nitropyrenes and
      their inhibitory effect on nitroreductase activity. This indicated that one of
      the possible antimutagenic mechanisms of Api or TA was to inactivate the
      metabolism of nitropyrenes. Two biological end-points, cytotoxicity and sister
      chromatid exchange (SCEs), were used to screen the antigenotoxic effects of these
      compounds in CHO cells. At the sub-cytotoxic dose, I3C, Api and TA all protected
      against the cytotoxicity induced by 1-NP and 1,6-DNP, but only TA and Api gave a
      significant reduction of the frequency of SCEs. Moreover, this reduction was
      found to be highly dose-dependent.

PMID- 1383742
TI  - Description of a new amplifiable shuttle vector for mutagenesis studies in human
      cells: application to N-methyl-N'-nitro-N-nitrosoguanidine-induced mutation
      spectrum.
AB  - In order to analyze the mechanisms of mutagenesis in human cells, we have
      established a human 293 cell-derived line containing a permanent mutagenesis
      target, the bacterial lacZ' gene, on an episomal EBV/SV40-based shuttle vector.
      This plasmid was maintained at a low copy number per cell which rendered it
      closer to an endogenous gene as compared to the usual transient shuttle vectors.
      Transient amplification of vectors, inside the host cell due to expression of the
      SV40 T-antigen, allowed the recovery of a large number of bacterial colonies
      transformed by plasmids extracted from human cells. Mutations produced in human
      host cells on the lacZ' locus were easily and rapidly scored and identified in
      bacteria using the blue/white color assay. Over a 6-month period in culture, we
      have shown that the lacZ' gene exhibited a low background frequency of point
      mutations (< 4.8 x 10(-6)). The efficiency of our system for detecting genotoxic
      induced mutations was investigated by treating cells with a potent mutagen, the
      direct alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). A
      significant increase (< 230-fold) in the frequency of single-base substitutions
      was observed after MNNG treatment. In total, 63 MNNG-induced independent
      mutations were characterized. All substitutions but one involved G:C base pairs
      with 89% being G:C to A:T transitions which is consistent with the MNNG mutagenic
      specificity already reported in bacteria and mammalian cells. Mutations were
      distributed along the two strands of the lacZ' gene and there was no obvious
      influence of either the 5' or the 3' flanking base near the G:C to A:T transition
      sites. The low spontaneous point mutation frequency on the mutagenesis locus and
      the ability to detect induced point mutations indicate that this system could be
      readily used in human mutagenesis studies at the molecular level.

PMID- 1383741
TI  - Bombesin impairs spindle function in mitotic V79 Chinese hamster cells by a
      receptor-dependent mechanism.
AB  - Bombesin belongs to a family of peptides acting as local hormones with roles in
      growth regulation, neural function and secretion. Upon binding to its receptor
      bombesin primarily elicits an increase of inositolphosphates and diacylglycerol,
      events leading to increased [Ca2+]i and activation of protein kinase C. When
      asynchronously growing V79 Chinese hamster cells were treated with bombesin in
      the 10(-9)-10(-7) M concentration range their content of inositolphosphates
      increased and so did the frequency of mitotic cells with abnormal chromosomal
      arrangements (c-mitoses). Both effects were abolished by simultaneous addition of
      the synthetic peptide antagonist D-Arg1,D-Phe5,D-Trpu7,9-Leu11-substance P that
      binds to certain bombesin receptors. These results demonstrate that the V79 cells
      most probably have receptors for bombesin and that the weak but significant c
      mitotic effect is mediated by such receptors.

PMID- 1383743
TI  - Structural basis of the in vivo induction of micronuclei.
AB  - The structural basis of the in vivo induction of micronuclei was examined with
      CASE, a structure-activity relational method. The CASE program identified a
      number of structures associated with this activity. When used to predict the
      activity of chemicals not included in the learning set, these structural
      determinants gave a concordance in excess of 83%. The existence of a structural
      basis for the induction of micronuclei will permit an investigation of the
      mechanistic basis of this phenomenon.

PMID- 1383744
TI  - Some factors affecting sister-chromatid differentiation (SCD) and sister
      chromatid exchange (SCE) in Hordeum vulgare.
AB  - A study of some factors affecting sister-chromatid differentiation (SCD) and
      sister-chromatid exchanges (SCE) in Hordeum vulgare is reported. After we studied
      the influence of 5-fluorodeoxyuridine (FdU) and growth temperature on SCE in
      barley cells, and the effect of FdU, growth temperature, the growth time of plant
      cells in 5-bromo-2-deoxyuridine (BrdU) solution on SCD, we found an experimental
      condition under which the frequency of SCE is lower, but the percentage of SCD is
      higher. Our data show that ascorbic acid, mitomycin C, adriamycin, and maleic
      hydrazide induce SCEs in cells of Hordeum vulgare by means of free radicals. This
      can be shown from the two observations: (1) sulfhydryl compounds such as cysteine
      and glutathione can completely or partially inhibit the SCEs induced by ascorbic
      acid, mitomycin C, adriamycin and maleic hydrazide; (2) the amounts of free
      radicals in root tips correlate with the frequencies of SCE in root tip cells.

PMID- 1383745
TI  - Overdispersion of aggregated genetic data.

PMID- 1383747
TI  - An evaluation of the E. coli K-12 uvrB/recA DNA repair host-mediated assay. I. In
      vitro sensitivity of the bacteria to 61 compounds.
AB  - A differential DNA repair test was evaluated in vitro, using derivatives of E.
      coli K-12 343/113 with the genotype uvrB-/recA- and uvrB+/recA+. The aim of this
      study was to characterize the sensitivity of the assay to different compounds in
      vitro and thereby provide information on the usefulness of this end-point as an
      indicator of genotoxicity in a host-mediated assay. Sixty-one compounds from
      diverse chemical groups were tested and of these 32 gave a positive result. The
      results obtained were compared with results from the Ames test and were in
      agreement for 49 out of the 61 compounds tested. Chemicals that were detected in
      this test but negative in the Ames test were 4-aminophenol, catechol,
      diethylstilbestrol, thioacetamide and thiourea. Seven of the compounds tested
      gave a negative result in E. coli but were positive in Salmonella. These were 4
      aminobiphenyl, benzo[a]pyrene, cyclophosphamide, 1-naphthylamine, N
      nitrosobutylpropylamine, quinoline and 2-toluidine. The performance of the in
      vitro test and reasons for the discrepant results with the Ames test are
      discussed. The overall concordance between the two tests was about 80%. On the
      basis of these results we consider these bacterial strains, and differential DNA
      repair as an end-point, to be sufficiently accurate as an indicator of
      genotoxicity in vitro and thereby also in vivo.

PMID- 1383746
TI  - Mutation of V79 cells by N-dialkylnitrosamines after activation by hamster
      pancreas duct cells.
AB  - Pancreas duct epithelial cells (DEC), isolated from hamsters and cultured for up
      to 25 days, were able to metabolize N-nitrosobis(2-oxopropyl)amine (BOP) to
      species that were mutagenic in V79 cells. There was no decline in the nitrosamine
      activating ability of DEC over the period of observation (25 d). DEC activated N
      nitrosobis(2-hydroxypropyl)amine (BHP), N-nitrosodiethylamine (DEN), N
      nitrosodimethylamine (DMN) and N-nitrosomethyl(2-oxopropyl)amine (MOP) and BOP in
      the same assay, although the mutation frequencies for BHP, DEN and DMN were
      barely different from that for the controls (4 +/- 1 mutants/10(6) cells). The
      mutation frequencies for a dose of 0.1 mM were BHP, 2 +/- 1; BOP, 113 +/- 7; DEN,
      8 +/- 1; DMN, 5 +/- 2; and MOP, 18 +/- 3 (mutants/10(6) cells; means +/- SE).
      When hepatocytes were used the mutation frequencies were BHP, 3 +/- 1; BOP, 60 +/
      3; DEN, 8 +/- 2; DMN, 8 +/- 2; and MOP, 121 +/- 10. BOP was toxic to the DEC at
      doses above 0.1 mM. Experiments in which co-factors were omitted from the medium
      suggested that an isoform(s) of the cytochrome P-450 IIIA family was involved,
      directly or indirectly, in BOP activation.

PMID- 1383748
TI  - An evaluation of the E. coli K-12 uvrB/recA DNA repair host-mediated assay. II.
      In vivo results for 36 compounds tested in the mouse.
AB  - The aim of this study was to further evaluate the E. coli K-12 DNA repair host
      mediated assay, as a short-term in vivo genotoxicity test, to be used as a
      complement to the micronucleus test in the routine testing of chemicals and
      drugs. The assay involves the administration of the test substance to mice by the
      route of choice, followed by the intravenous administration of a mixture of DNA
      repair deficient and proficient derivatives of E. coli K-12. After an incubation
      period the relative survival of the two strains was determined in blood, liver,
      lungs, kidneys and testes of the host. A significant preferential reduction of
      the DNA repair deficient strain in any organ indicates that the test substance
      possesses genotoxic properties. A total of 36 substances, 26 carcinogens, 4 weak
      or non-carcinogens and 6 unclassified substances, were tested in this assay.
      Positive results were obtained for 23 compounds. Of the carcinogens 18 were
      positive and of the non-carcinogens 3 were negative. The overall concordance
      between the assay and carcinogenicity was 72%. In general, alkylating agents and
      direct-acting nitroso compounds showed genotoxic activity in all organs tested,
      while the other substances were positive in a limited number of organs. With oral
      administration, which was the most commonly used administration route in the
      study, the organ showing a positive response most often was the blood. The
      results from the present study were compared with results from the micronucleus
      test, which were available for 26 of the substances. Results were in agreement
      for 15 of the substances, while 8 substances were positive in the present assay
      and negative in the micronucleus test: 4-aminobiphenyl, 2-anisidine,
      epichlorohydrin, formaldehyde, 1- and 2-naphthylamine, 2-nitrophenylenediamine
      and 4-nitroquinoline-N-oxide. The substances negative in the E. coli DNA repair
      host-mediated assay, but positive in the micronucleus test were: benzene,
      catechol and cyclophosphamide. It is concluded from this evaluation that the E.
      coli K-12 DNA repair host-mediated assay detects a number of carcinogens that are
      negative in the micronucleus test, while detecting most of the compounds that are
      positive in the latter. The advantages of this test are that differential DNA
      repair measures a broad spectrum of genetic damage, an in vitro/in vivo
      comparison is possible with the same test organisms, results can be obtained from
      various organs and the test is rapid.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1383749
TI  - Genotoxic potential of the organochlorine insecticide lindane (gamma-BHC): an in
      vivo study in chicks.
AB  - The purpose of this work was to evaluate the genotoxic potential of lindane
      (gamma-isomer of benzene hexachloride (BHC)) in chicken in vivo tests: the bone
      marrow chromosome aberration and micronucleus tests. With the highest dose (100
      mg/kg) a significant enhancement of chromosome aberrations was noticed after 24
      and 48 h and with the second highest dose (75 mg/kg) after 24 h. A significant
      increase in the incidence of micronuclei in bone marrow cells was induced by all
      three doses (100, 75 and 50 mg/kg) given either intraperitoneally or orally while
      in peripheral erythrocytes only the two higher intraperitoneal doses (100 and 75
      mg/kg) gave significant increases. On the basis of these results, lindane may be
      considered genotoxic in this test system and it is suggested that the chick in
      vivo system may be used as an alternative to a mammalian system for screening
      environmental chemicals for genotoxicity.

PMID- 1383750
TI  - Use of a newly developed tester strain Salmonella typhimurium NM2009 for the
      study of metabolic activation of carcinogenic aromatic amines by rat liver
      microsomal cytochrome P-450 enzymes.
AB  - Using an O-acetyltransferase-overexpressing strain Salmonella typhimurium NM2009
      we measured the activities for metabolic activation of several carcinogenic
      arylamines to genotoxic products by rat liver microsomal cytochrome P-450
      enzymes, and compared them with the activities obtained in the original tester
      strain Salmonella typhimurium TA1535/pSK1002 or the O-acetyltransferase-defective
      strain Salmonella typhimurium NM2000. Since all of the tester strains had
      introduced the umuC'-'lacZ gene, we could detect the genotoxic activities by
      measuring bacterial beta-galactosidase activity resulting from the DNA damage. In
      the O-acetyltransferase-defective strain NM2000 most of the arylamines tested
      showed weak responses in inducing umu gene expression after metabolic activation
      by liver microsomes. The strain NM2009, on the other hand, was found to be highly
      sensitive towards a variety of aromatic amines, and these activities were greater
      than those seen in the original tester strain S. typhimurium TA1535/pSK1002. The
      chemicals which marked responses in strain NM2009 include 2-aminoanthracene, 6
      aminochrysene, 2-aminofluorene, 2-acetylaminofluorene, 3-methoxy-4
      aminoazobenzene, O-aminoazotoluene, Glu-P-1, Trp-P-2, A alpha C, MeA alpha C,
      MeIQ, MeIQx and IQ. Of these procarcinogens tested MeIQ, MeIQx and IQ also showed
      strong cytotoxic effects in S. typhimurium NM2009 after metabolic activation by
      liver microsomes. Only PhIP was the substrate showing similar responses in
      strains TA1535/pSK1002 and NM2009. The results with the reconstituted
      monooxygenase system containing purified cytochrome P-450 enzymes support the
      above findings obtained with the liver microsomal enzyme system. Thus, the
      usefulness of the newly developed strain NM2009 for the detection of reactive
      metabolites of several carcinogenic aromatic amines after metabolism by the liver
      microsomal cytochrome P-450-linked monooxygenase system has been ascertained.

PMID- 1383752
TI  - Environmental mutagenesis and related subjects including methodology.

PMID- 1383751
TI  - The ability of alkylating agents to induce micronucleated reticulocytes in mice.

PMID- 1383753
TI  - A sensitive umu test system for the detection of mutagenic nitroarenes in
      Salmonella typhimurium NM1011 having a high nitroreductase activity.
AB  - A sensitive umu test system for the detection of mutagenic nitroarenes has been
      developed using a new tester strain Salmonella typhimurium NM1011 having a high
      nitroreductase activity. The new strain was constructed by subcloning the
      bacterial nitroreductase gene into a plasmid pACYC184 and introducing the plasmid
      into the original strain S. typhimurium TA1535/pSK1002 harboring a fusion gene
      umuC'-'lacZ (pSK1002). Thus, the tester strain enabled us to monitor the
      genotoxic activities of various nitroarene compounds by measuring the beta
      galactosidase activity in the cells. The sensitivity of strain NM1011 was
      compared with that of the parent tester strain S. typhimurium TA1535/pSK1002 or a
      nitroreductase-deficient strain S. typhimurium NM1000 with respect to the
      induction of umuC gene expression by 17 mutagenic nitroarenes. The newly
      developed strain with high nitroreductase activity had about 3 times higher
      nitrofurazone-reductase activity than the parent strain and was highly sensitive
      to the compounds 2-nitrofluorene, 1-nitronaphthalene, 2-nitronaphthalene, 1
      nitropyrene, m-dinitrobenzene, 4,4'-dinitrobiphenyl, 3-nitrofluoranthene, 3,7
      dinitrofluoranthene, 3,9-dinitrofluoranthene, 5-nitroacenaphthene and 2,4
      dinitrotoluene. By contrast, the enzyme-deficient strain did not show any
      considerable response to 2-nitrofluorene, m-dinitrobenzene, 1-nitronaphthalene, 2
      nitronaphthalene, 1-nitropyrene, 4,4'-dinitrobiphenyl, 3-nitrofluoranthene, 3,7
      dinitrofluoranthene, 2,4-dinitrotoluene and 5-nitroacenaphthene. These results
      suggest that the newly developed tester strain with high nitroreductase activity
      is very useful for the detection of potent mutagenic nitroarene compounds.

PMID- 1383754
TI  - Progressive loss of cytochrome c oxidase in the human extraocular muscles in
      ageing--a cytochemical-immunohistochemical study.
AB  - Cytochrome c oxidase (complex IV of the respiratory chain) was studied
      histochemically in autoptic human extraocular muscles (n = 135), revealing
      randomly distributed single fibers without enzyme activity. The enzyme defect was
      expressed in all the mitochondria of an involved fiber as evidenced by
      ultracytochemistry. Succinate dehydrogenase showed normal histochemical
      reactivity. The defects occurred already in the second decade and were regularly
      seen from the third decade on. The defect density (defects/mm2) increased from
      approx. 1/mm2 below the fifth decade to about 4/mm2 in advanced age (P = 0.000).
      The highest defect density was observed in the levator palpebrae muscle. On the
      whole, the defect density was about 5-6 times higher in the extraocular muscles
      than in the limb muscle, diaphragm and heart (Muller-Hocker, 1989, 1990).
      Immunocytochemical detection of cytochrome c oxidase showed that loss of
      cytochrome c oxidase activity was due to an almost complete absence of both
      nuclear and mitochondria subunits of the enzyme. The results document different
      organ and heterogenic cellular sensitivity to the age-related loss of cytochrome
      c oxidase. The loss of both mitochondrial and nuclear subunits indicates that
      nuclear factors are most probably involved in the decline of the respiratory
      chain function in senescence.

PMID- 1383755
TI  - Respiratory chain failure in adult muscle fibres: relationship with ageing and
      possible implications for the neuronal pool.
AB  - A histochemical analysis of mitochondrial enzyme activity was carried out in 103
      human diaphragmatic skeletal muscles from 49 subjects of different ages, obtained
      either at the time of abdominal surgery or at necropsy. Evidence of respiratory
      failure (cytochrome oxidase negativity) was seen in occasional fibres from the
      fourth decade on with an approximate 10-fold increase between the fourth and
      ninth decade (0.16% to 2.85%). A similar incidence of mitochondrial failure in
      CNS neurones to that documented in skeletal muscle could easily account for
      attrition of 25% of neurones over a 50-year period as reported in the literature.
      Possible theoretical relationships between morphological markers of mitochondrial
      failure and cell attrition are explored. While the projections from muscle to
      neurone are somewhat speculative, it is clear that if a similar extent of
      mitochondrial pathology exists in the brain to that documented in skeletal
      muscle, this could easily account for neuronal loss in the ageing brain.

PMID- 1383756
TI  - Mitochondrial function in neurodegeneration and ageing.
AB  - The mitochondrial respiratory chain and oxidative phosphorylation system are
      responsible for the production of ATP by aerobic metabolism. Defects of the
      respiratory chain are increasingly recognised as important causes of human
      disease, and neurodegenerative disorders in particular. This article will seek to
      review the clinical and biochemical effects of respiratory chain defects, and
      summarise what is known about the molecular mechanisms that underlie them.
      Increasing age is also associated with a decline in mitochondrial function. The
      biochemical correlates of this dysfunction and the possible molecular defects
      that may cause it will also be reviewed.

PMID- 1383757
TI  - Mitochondrial DNA alterations as ageing-associated molecular events.
AB  - Mitochondrial DNA (mtDNA) is a naked double-stranded circular extrachromosomal
      genetic element continuously exposed to the matrix that contains great amounts of
      reactive oxygen species and free radicals. The age-dependent decline in the
      capability and capacity of mitochondria to dispose these oxy-radicals will render
      mtDNA more vulnerable to mutations during the ageing process. During the past 3
      years, more than 10 different types of deletions have been identified in the
      mtDNA of various tissues of old humans. Some of them were found only in a certain
      tissue but some others appeared in more than one organ or tissue. The 4977-bp
      deletion is the most prevalent and abundant one among these deletions. Skeletal
      muscle is the target tissue of most ageing-associated mtDNA deletions and has
      often been found to carry multiple deletions. The onset age of the various
      deletions in mtDNA varies greatly with individual and type of the deletion. The
      4977-bp deletion has been independently demonstrated to occur in the mtDNA of
      various tissues of the human in the early third decade of life. However, the 7436
      bp deletion was only detected in the heart mtDNA of human subjects in their late
      thirties. The others appeared only in older humans over 40 years old. No apparent
      sex difference was found in the onset age of these ageing-associated mtDNA
      deletions. The various ageing-associated deletions could be classified into two
      groups. Most of the deletions belong to the first group, in which the 5'- and 3'
      end breakpoints of the deletion are flanked by 4-bp or longer direct repeats. The
      deletion in the second group occurs less frequently and shows no distinct repeat
      sequences flanking the deletion sites. These two groups of mtDNA deletions may
      occur by different mechanisms. The first group is most probably caused by
      internal recombination or slippage mispairing during replication of mtDNA by the
      D-loop mechanism. The deleted mtDNA and the deleted DNA fragment may be further
      degraded or escape from the mitochondria and get translocated into the nucleus.
      The latter route has been substantiated by many observations of inserted mtDNA
      sequences in the nuclear DNA. Thus, the fragments of migrating mtDNA may change
      the information content and expression level of certain nuclear genes and thereby
      promote the ageing process or cause cancer. Similar ageing-associated alterations
      of mtDNA have also been observed in aged animals and plants. I suggest that mtDNA
      deletions and other mutations to be discovered are molecular events generally
      associated with the ageing process.

PMID- 1383758
TI  - Deleterious mitochondrial DNA mutations accumulate in aging human tissues.
AB  - This paper reviews the current state of knowledge of the contribution of
      mitochondrial DNA (mtDNA) mutations to the phenotype of aging. Its major focus is
      on the discovery of deletions of mtDNA which previously were thought to occur
      only in individuals with neuromuscular disease. One particular deletion
      (mtDNA4977) accumulates with age primarily in non-dividing cells such as muscle
      and brain of normal individuals. The level of the deletion rises with age by more
      than 1000 fold in heart and brain and to a lesser extent in other tissues. In the
      brain, different regions have substantially different levels of the deletion.
      High levels of accumulation of the deletion in tissues are correlated with high
      oxygen consumption. We speculate that oxidative damage to mtDNA may be
      'catastrophic'; mutations affecting mitochondrially encoded polypeptides involved
      in electron transport could increase free radical generation leading to more
      mtDNA damage.

PMID- 1383759
TI  - Association of mitochondrial DNA damage with aging and coronary atherosclerotic
      heart disease.
AB  - The role of somatic mitochondrial DNA (mtDNA) damage in human aging and
      progressive diseases of oxidative phosphorylation (OXPHOS) was examined by
      quantitating the accumulation of mtDNA deletions in normal hearts and hearts with
      coronary atherosclerotic disease. In normal hearts, mtDNA deletions appeared
      after 40 and subsequently accumulated with age. The common 4977 nucleotide pair
      (np) deletion (mtDNA4977) reached a maximum of 0.007%, with the mtDNA7436 and
      mtDNA10,422 deletions appearing at the same time. In hearts deprived of
      mitochondrial substrates due to coronary artery disease, the level of the
      mtDNA4977 deletion was elevated 7-220-fold over age-matched controls, with the
      mtDNA7436 and mtDNA10,422 deletions increasing in parallel. This cumulative mtDNA
      damage was associated with a compensatory 3.5-fold induction of nuclear OXPHOS
      gene mRNA and regions of ischemic hearts subjected to the greatest work load
      (left ventricle) showed the greatest accumulation of mtDNA damage and OXPHOS gene
      induction. These observations support the hypothesis that mtDNA damage does
      accumulate with age and indicates that respiratory stress greatly elevates
      mitochondrial damage.

PMID- 1383760
TI  - Mitochondrial DNA copy number and mitochondrial DNA deletion in adult and
      senescent rats.
AB  - In order to understand the cause of the reduced mitochondrial DNA transcription
      in heart and brain of senescent rat previously reported, we focused our attention
      on the content and structure of rat mitochondrial DNA in adult and senescent
      rats. The estimate of the mtDNA copy number in liver, heart and brain of adult
      and senescent rats showed that in all organs examined the senescent individuals
      have a mtDNA content higher than the adult counterparts. The analysis of mtDNA
      structural changes involved the search for point mutations and large deletions.
      As for the first case, the determination of the nucleotide sequence of many
      independent clones containing two mtDNA restriction fragments isolated from rat
      cerebral hemispheres did not show any sequence difference between adult and
      senescent individuals. However, analysis of mtDNA deletions by the polymerase
      chain reaction in liver and brain of adult and senescent rats identified a small
      population of mtDNA molecules harboring a deletion of 4834 bp. The estimate of
      the proportion of deleted molecules in the liver showed that they represent 0.02%
      and 0.0005% of total mtDNA in senescent and adult rat liver respectively.
      Therefore, a mtDNA deletion also accumulates in the rat during aging. This result
      supports the hypothesis of the accumulation of deleted mtDNA molecules in aging.
      However, the low percentage of deleted mtDNA molecules already found and the
      reversibility of the reduced mitochondrial DNA transcription in senescent rat
      raise doubts on the primary role of the irreversibly damaged mtDNA molecules in
      aging. Deleted mtDNA molecules along with changes caused by lipid peroxidation of
      mitochondrial membranes might contribute to the overall decline of mitochondrial
      function.

PMID- 1383761
TI  - Mitochondrial DNA mutation and the ageing process: bioenergy and pharmacological
      intervention.
AB  - A comprehensive hypothesis concerning the contribution of mitochondrial DNA
      (mtDNA) mutations to the human ageing process is reviewed and the implications
      for cellular bioenergy loss and pharmacological therapy are considered. The
      central idea is that random mutations in the population of mtDNA molecules of
      each cell occur throughout life, and that this is a major contributor to the
      gradual loss of cellular bioenergy capacity within tissues and organs, associated
      with general senescence and diseases of ageing. An elaboration of four major
      aspects of the general proposition, together with relevant supporting data, is
      presented. (1) An extensive array of deletions in mtDNA of many tissues of humans
      and other mammals has been observed to occur in an age-related manner. (2) The
      preservation and selection of fully functional mtDNA molecules in the female germ
      line cells is proposed to occur via a human mtDNA cycle, in which selective
      amplification of a limited number of mtDNA templates occurs during oocyte
      development. This proposal explains the endowment of normal neonates with a mtDNA
      complement minimally contaminated by damaged mtDNA molecules. The phenomena of
      maternal inheritance and rapid fixation of sequence variants of mtDNA in mammals,
      as well as selection of cells based on mitochondrial function, are taken into
      account. (3) Tissue bioenergy mosaics result from accumulated mtDNA damage during
      ageing, representing different rates of cellular bioenergy loss within individual
      cells of a tissue. The random segregation of mtDNA during cell division will also
      further contribute to the tissue energy mosaic. Cells unable to meet their
      particular bioenergy demand will become non-functional, leading to cell death;
      the bioenergy threshold is different for the various cell types in the tissues of
      the body. (4) In order to bioenergetically resuscitate cells and tissues
      suffering from impaired mitochondrial functions as a result of the ageing
      process, we propose that redox compounds may be used therapeutically in the
      pharmacological configurations of a by-pass strategy or as a redox sink therapy.
      The role of these compounds is to maintain at least part of the mitochondrial
      respiratory chain function (by-pass) as well as to maintain adequate levels of
      cellular NAD+ (redox sink) for ATP synthesis, predominantly by the cytosolic
      glycolytic pathway, with some contribution from mitochondrial oxidative
      phosphorylation.

PMID- 1383762
TI  - An update on the mitochondrial-DNA mutation hypothesis of cell aging.
AB  - Our electron microscopic study of aging insects and mammals suggests that
      metazoan senescence is linked to a gradual process of mitochondrial breakdown
      (and lipofuscin accumulation) in fixed postmitotic cells. This led us to propose
      in the early 1980s an oxyradical-mitochondrial DNA damage hypothesis, according
      to which metazoan aging may be caused by mutation, inactivation or loss of the
      mitochondrial genome (mtDNA) in irreversibly differentiated cells. This
      extranuclear somatic gene mutation concept of aging is in agreement with the fact
      that mtDNA synthesis takes place at the inner mitochondrial membrane near the
      sites of formation of highly reactive oxygen species and their products.
      Mitochondrial DNA may be unable to counteract the damage inflicted by those by
      products of respiration because, in contrast to the nuclear genome, it lacks
      excision and recombination repair. Since mtDNA contains the structural genes for
      13 hydrophobic proteins of the respiratory chain and ATP synthase as well as
      mitochondrial rRNAs and tRNAs, damage to this organellar genome will decrease or
      prevent the 'rejuvenation' of the mitochondria through the process of
      macromolecular turnover and organelle fission. Thus deprived of the ability to
      regenerate their mitochondria, the fixed postmitotic cells will sustain a
      decrease in the number of functional organelles, with resulting decline in ATP
      production. At higher levels of biological organization, this will lead to a loss
      in the bioenergetic capacity of cells, with concomitant decreases in ATP
      dependent protein synthesis and specialized physiological function, thus paving
      the way for age related degenerative diseases. The above concept is supported by
      a wealth of recent observations confirming the genomic instability of
      mitochondria and suggesting that animal and human aging is accompanied by mtDNA
      deletions and other types of injury to the mitochondrial genome. Our hypothesis
      of mtDNA damage is integrated with the classic concepts of Weissman and Minot in
      order to provide a preliminary explanation of the evolutionary roots of aging and
      reconcile the programed and stochastic views of metazoan senescence.

PMID- 1383763
TI  - Evidence for and against the causal involvement of mitochondrial DNA mutation in
      mammalian ageing.
AB  - Current experimental evidence on the role of mitochondrial DNA mutation in ageing
      is assessed alongside reports implicating other genetic and non-genetic causes,
      including inter-relationships between the mitochondrial and nuclear genomes and
      their potential effect on mitochondrial structure and function. The role of a 5
      kb mtDNA deletion, identified as age-dependent in a variety of human and other
      mammalian species, is specifically evaluated in the context of its functional
      effect in mitotic and non-mitotic adult tissue. Downstream effects of
      mitochondrial decline are considered in terms of the maintenance of ATP
      production. Associated sequelae then are discussed specifically with reference to
      restrictions in the supply of ribose moieties for DNA and RNA synthesis, and to
      disruption of NADPH production and hence cellular anti-oxidant defences.

PMID- 1383764
TI  - New evidence for the insertion of mitochondrial DNA into the human genome:
      significance for cancer and aging.
AB  - We have observed and characterized in detail two cases of mitochondrial DNA
      fragments which have inserted into the nucleus of HeLa cells. In one case three
      non-sequential but contiguous regions of mitochondrial DNA with 92% homology to
      human cytoplasmic mitochondrial DNA inserted into the nuclear genome. In the
      second case the mitochondrial DNA sequence encoding cytochrome c oxidase subunit
      III was contiguous with and 5' of exons 2 and 3 of the c-myc oncogene and the
      chimeric gene was transcribed. Models are presented that describe mechanisms for
      the transfer of mitochondrial DNA into the nucleus involving fragmentation of
      mitochondrial DNA through aging and/or oxidative damage, anomalous processing or
      escape of mitochondrial DNA and RNA fragments from autophagic vacuoles, and
      insertion of mitochondrial DNA sequences, in some instances after reverse
      transcription of mitochondrial RNA, into the nuclear genome.

PMID- 1383765
TI  - Structural dynamics of the mitochondrial compartment.
AB  - The metabolic activities of mitochondria have been extensively characterized.
      However, there is much less known about the morphogenic changes of the
      mitochondrial compartment during growth, development and aging of the cell and
      the consequences of those structural changes on cellular metabolism. There is a
      growing body of evidence for interactions of mitochondria with cytoskeletal
      components and changes of mitochondrial structure during development and in
      response to changing environmental conditions. Segregation and recombination of
      mitochondrial genomes are also processes dependent upon the dynamic nature of the
      mitochondrial compartment. These regulatory and structural aspects of
      mitochondrial compartment dynamics will play an important role in the analysis of
      mitochondrial function and pathology.

PMID- 1383766
TI  - Lipid peroxidation and mtDNA degeneration. A hypothesis.
AB  - End-products of lipid peroxidation accumulate during the life of somatic cells.
      It is hypothesized that genotoxic intermediates of lipid peroxidation may have a
      role in causing age-associated DNA mutations. Such mutations are likely to accrue
      in the mitochondrial genome because it, unlike nuclear DNA, is not protected by
      histones and repair systems. In addition, it is located near the mitochondrial
      membrane where lipid peroxidation can be initiated by free radicals produced by
      the mitochondrial electron transport system. This idea is supported by in vitro
      experiments which show that mitochondrial DNA is damaged when mitochondria
      undergo lipid peroxidation.

PMID- 1383768
TI  - Free radical theory of aging.
AB  - Free radical reactions are ubiquitous in living things. Studies on the origin and
      evolution of life provide a reasonable explanation for the prominent presence of
      this unruly class of chemical reactions. These reactions have been implicated in
      aging. This phenomenon is the accumulation of changes responsible for the
      sequential alterations that accompany advancing age and the associated
      progressive increases in the chance of disease and death. Aging changes are
      attributed to the environment and disease, and to an inborn process, the aging
      process. The latter produces aging changes at an exponentially increasing rate
      with advancing age. Past improvements in general living conditions have decreased
      the chances for death so that they are now near limiting values in the developed
      countries. In these countries the intrinsic aging process is the major cause of
      disease and death after about age 28. The free radical theory of aging postulates
      that aging changes are caused by free radical reactions. The data supporting this
      theory indicate that average life expectancy at birth may be increased by 5 or
      more years, by nutritious low caloric diets supplemented with one or more free
      radical reaction inhibitors.

PMID- 1383767
TI  - Reactive oxygen and DNA damage in mitochondria.
AB  - During the last decade the importance of reactive oxygen species as major
      contributors to various types of cancer, heart diseases, cataracts, Parkinson's
      and other degenerative diseases that come with age, and to natural aging has
      become apparent. Mitochondria are the most important intracellular source of
      reactive oxygen. Mitochondrial DNA is heavily damaged by reactive oxygen at the
      bases, as indicated by the high steady-state level of 8-hydroxydeoxyguanosine,
      the presence of which causes mispairing and point mutations. Mitochondrial DNA is
      also oxidatively fragmented to a certain extent. Conceivably, such fragmentation
      relates to deletions found in mitochondrial DNA. Point mutations and deletions
      have recently been shown to be etiologically linked to several human diseases and
      natural aging. Future studies should address the causal relationship between
      mitochondrial dysfunction, production of reactive oxygen species, and aging.

PMID- 1383769
TI  - Role of oxidative stress in Drosophila aging.
AB  - We review the role that oxidative damage plays in regulating the lifespan of the
      fruit fly, Drosophila melanogaster. Results from our laboratory show that the
      lifespan of Drosophila is inversely correlated to its metabolic rate. The
      consumption of oxygen by adult insects is related to the rate of damage induced
      by oxygen radicals, which are purported to be generated as by-products of
      respiration. Moreover, products of activated oxygen species such as hydrogen
      peroxide and lipofuscin are higher in animals kept under conditions of increased
      metabolic rate. In order to understand the in vivo relationship between oxidative
      damage and the production of the superoxide radical, we generated transgenic
      strains of Drosophila melanogaster that synthesize excess levels of enzymatically
      active superoxide dismutase. This was accomplished by P-element transformation of
      Drosophila melanogaster with the bovine cDNA for CuZn superoxide dismutase, an
      enzyme that catalyzes the dismutation of the superoxide radical to hydrogen
      peroxide and water. Adult flies that express the bovine SOD in addition to native
      Drosophila SOD are more resistant to oxidative stresses and have a slight but
      significant increase in their mean lifespan. Thus, resistance to oxidative stress
      and lifespan of Drosophila can be manipulated by molecular genetic intervention.
      In addition, we have examined the ability of adult flies to respond to various
      environmental stresses during senescence. Resistance to oxidative stress, such as
      that induced by heat shock, is drastically reduced in senescent flies. This loss
      of resistance is correlated with the increase in protein damage generated in old
      flies by thermal stress and by the insufficient protection from cellular defense
      systems which includes the heat shock proteins as well as the oxygen radical
      scavenging enzymes. Collectively, results from our laboratory demonstrate that
      oxidative damage plays a role in governing the lifespan of Drosophila during
      normal metabolism and under conditions of environmental stress.

PMID- 1383770
TI  - Age-related changes in antioxidant enzymes and lipid peroxidation in brains of
      control and transgenic mice overexpressing copper-zinc superoxide dismutase.
AB  - The aim of our study was first to obtain a comprehensive profile of the brain
      antioxidant defense potential and peroxidative damage during aging. We
      investigated copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide
      dismutase (MnSOD), seleno-dependent glutathione peroxidase (GSH-PX), glutathione
      reductase (GSSG-R) activities, endogenous and in vitro stimulated lipid
      peroxidation in 40 brains of control mice divided into 3 age groups: 2 months
      (young), 12 months (middle-aged) and 28 months (old). We found a positive
      correlation between age and activities of CuZnSOD (r = 0.47; P < 0.01) and GSH-PX
      (r = 0.72; P < 0.0001). CuZnSOD and GSH-PX activities are independently regulated
      during brain aging since temporal changes of these two enzymes do not correlate.
      No modification in MnSOD activity and basal lipid peroxidation was observed as a
      function of age. Nevertheless, stimulated lipid peroxidation was significantly
      higher at 12 months (6.53 +/- 0.71 mumole MDA/g tissue) than at 2 months (5.69 +/
      0.90) and significantly lower at 28 months (5.13 +/- 0.33) than at 12 months.
      Second, we used genetic manipulations to construct transgenic mice that
      specifically overexpress CuZnSOD to understand the role of CuZnSOD in neuronal
      aging. The human CuZnSOD transgene expression was stable during aging. The
      increased CuZnSOD activity in the brain (1.9-fold) of transgenic mice resulted in
      an enhanced rate of basal lipid peroxidation and in increased MnSOD activity in
      the 3 age groups. Other antioxidant enzymes did not exhibit modifications
      indicating the independence of the regulation between CuZnSOD and glutathione
      related enzymes probably due to their different cellular localization in the
      brain.

PMID- 1383771
TI  - Mitochondrial production of pro-oxidants and cellular senescence.
AB  - Mitochondria are the major intracellular producers of O2- and H2O2. The level of
      oxidative stress in cells, as indicated by the in vivo exhalation of alkanes and
      the concentration of molecular products of oxy-radical reactions, increases
      during aging in mammals as well as insects. In this paper, we discuss the
      relationship between mitochondrial generation of O2- and H2O2, and the aging
      process. The rate of mitochondrial O2- and H2O2 generation increases with age in
      houseflies and the brain, heart and liver of rat. This rate has been found to
      correspond to the life expectancy of flies and to the maximum life span potential
      (MLSP) of six different mammalian species, namely, mouse, rat, guinea pig,
      rabbit, pig and cow. In contrast, the level of antioxidant defenses provided by
      activities of superoxide dismutase, catalase, glutathione peroxidase and
      glutathione concentration neither uniformly declines with age nor corresponds to
      variations in MLSP of different mammalian species. It is argued that the rate of
      mitochondrial O2- and H2O2 generation rather than the antioxidant level may act
      as a longevity determinant.

PMID- 1383772
TI  - Oxidative and other DNA damages as the basis of aging: a review.
AB  - DNA damages occur continuously in cells of living organisms. While most of these
      damages are repaired, some accumulate. In particular, there is evidence for DNA
      damage accumulation in non-dividing cells of mammals. These accumulated DNA
      damages probably interfere with RNA transcription. We consider that the decline
      in the ability of DNA to serve as a template for gene expression is the primary
      cause of aging. Oxidative DNA damages are among the best documented and prevalent
      DNA damages and are likely to be a prominent cause of aging.

PMID- 1383774
TI  - Oxidative damage to DNA in mammalian chromatin.
AB  - Efforts have been made to characterize and measure DNA modifications produced in
      mammalian chromatin in vitro and in vivo by a variety of free radical-producing
      systems. Methodologies incorporating the technique of gas chromatography/mass
      spectrometry have been used for this purpose. A number of products from all four
      DNA bases and several DNA-protein cross-links in isolated chromatin have been
      identified and quantitated. Product formation has been shown to depend on the
      free radical-producing system and the presence or absence of oxygen. A similar
      pattern of DNA modifications has also been observed in chromatin of cultured
      mammalian cells treated with ionizing radiation or H2O2 and in chromatin of
      organs of animals treated with carcinogenic metal salts.

PMID- 1383773
TI  - DNA damage and repair in brain: relationship to aging.
AB  - The usefulness of conducting DNA damage and repair studies in a postmitotic
      tissue like brain is emphasized. We review studies that use brain as a tissue to
      test the validity of the DNA damage and repair hypothesis of aging. As far as the
      accumulation of age dependent DNA damage is concerned, the data appear to
      overwhelmingly support the hypothesis. However, attempts to demonstrate a decline
      in DNA repair capacity as a function of age are conflicting and equally divided.
      Possible reasons for this discrepancy are discussed. It is suggested that
      assessment of the repair capacity of neurons with respect to a specific type of
      damage in a specific gene might yield more definitive answers regarding the role
      of DNA repair potential in the aging process and as a longevity assurance system.

PMID- 1383775
TI  - Chemical and biochemical postlabeling methods for singling out specific oxidative
      DNA lesions.
AB  - A survey of the main available chemical and biochemical postlabeling assays for
      measuring oxidative DNA damage is reported. Two main approaches, radio and
      fluorescent postlabeling, have been used in order to reach a high level of
      sensitivity of detection. This is required for the measurement of DNA damage
      within cells and tissues upon exposure to agents of oxidative stress. Most of the
      methods are based on liquid chromatographic separation of defined DNA
      modifications following either acidic hydrolysis or enzymic digestion of DNA. In
      a subsequent step, the isolated base or sugar damages are either radiolabeled or
      made fluorescent by chemical or enzymatic reactions. Emphasis is placed on the
      recently developed high performance liquid chromatographic 32P-postlabeling
      assay, which allows the specific and sensitive measurement of various base
      damages including adenine N-1 oxide and 5-hydroxymethyluracil at the level of one
      modification per 10(7) normal bases in a sample size of 1 microgram of DNA.
      Examples of application of radioactive postlabeling to the measurement of DNA
      base damage following exposure of human cells to oxidizing agents including
      hydrogen peroxide and UVA radiation are provided.

PMID- 1383776
TI  - Formation of ribonucleotides in DNA modified by oxidative damage in vitro and in
      vivo. Characterization by 32P-postlabeling.
AB  - Oxygen free radicals generated by the interaction of Fe2+ and H2O2 (Fenton
      reaction) are capable of reacting with DNA bases, which may induce premutagenic
      and precarcinogenic lesions. Products formed in DNA by such reactions have been
      characterized as hydroxylated derivatives of cytosine, thymine, adenine, and
      guanine and imidazole ring-opened derivatives of adenine and guanine. As shown
      here by 32P-postlabeling, incubation of DNA under Fenton reaction conditions gave
      rise to additional oxidation products in DNA that were characterized as putative
      ribonucleosides by enzymatic hydrolysis of the oxidized DNA, 32P-postlabeling,
      and co-chromatography in multiple systems with authentic markers. Formation of
      these products in DNA was enhanced by the presence of L-ascorbic acid in the
      reaction mixtures and their total amounts were similar to those of the major DNA
      oxidation product, 8-hydroxy-2'-deoxyguanosine. The ribonucleoside guanosine was
      also formed in kidney DNA of male rats treated with ferric nitrilotriacetate, a
      renal carcinogen. It is postulated that ribonucleotides alter conformation and
      function of DNA and thus their presence in DNA may lead to adverse health
      effects.

PMID- 1383777
TI  - Singlet oxygen induced DNA damage.
AB  - Singlet oxygen generated by photoexcitation and by chemiexcitation selectively
      reacts with the guanine moiety in nucleosides (kq + kr about 5 x 10(6) M-1s-1)
      and in DNA. The oxidation products include 8-oxo-7-hydro-deoxyguanosine (8-oxodG;
      also called 8-hydroxydeoxyguanosine) and 2,6-diamino-4-hydroxy-5
      formamidopyrimidine (FapyGua). Singlet oxygen also causes alkali-labile sites and
      single-strand breaks in DNA. The biological consequences include a loss of
      transforming activity as studied with plasmids and bacteriophage DNA, and
      mutagenicity and genotoxicity. Employing shuttle vectors, it was shown that
      double-stranded vectors carrying singlet oxygen induced lesions seem to be
      processed in mammalian cells by DNA repair mechanisms efficient in preserving the
      biological activity of the plasmid but highly mutagenic in mammalian cells.
      Biological protection against singlet oxygen is afforded by quenchers, notably
      carotenoids and tocopherols. Major repair occurs by excision of the oxidized
      deoxyguanosine moieties by the Fpg protein, preventing mismatch of 8-oxodG with
      dA, which would generate G:C to T:A transversions.

PMID- 1383778
TI  - Interaction of singlet oxygen with DNA and biological consequences.
AB  - To study the interaction of singlet oxygen (1O2) with DNA and the biological
      consequences of 1O2-induced DNA damage, we used the thermodissociable
      endoperoxide of 3,3'-(1,4 naphthalidene) dipropionate (NDPO2) as a generator of
      free 1O2 in reactions with (1) 2'-deoxynucleoside 3'-monophosphates (dNps), (2)
      an oligonucleotide (16-mer) having one deoxyguanine (dG), (3) native and
      denaturated rat kidney DNA and (4) single-stranded (ss) and double-stranded (ds)
      bacteriophage M13mp10 DNA. Using both anion exchange and reversed phase HPLC and
      32P-postlabeling analyses, it was found that exposure of the various dNps to
      chemically generated 1O2 led to a detectable reaction with dGp and not with dAp,
      dCp, d5mCp or Tp. The reaction with dGp led to degradation of this nucleotide and
      the formation of a large number of reaction products, one of which could be
      identified as 7-hydro-8-oxo-2'-deoxyguanosine 3'-monophosphate (8-oxo-dGp). A
      second product could tentatively be identified as a formamido pyrimidine
      derivative of dGp (Fapy-dGp). When ss DNA, ds DNA or the oligonucleotide were
      exposed to 1O2, the formation of 8-oxo-dG could also be demonstrated. With the
      oligonucleotide, we found a so far unidentified reaction product. Under the same
      reaction conditions the yield of 8-oxo-dG was about 8-fold higher in ss DNA than
      in ds DNA. In ss DNA 8-oxo-dG seemed to be a more prominent product than in the
      case of reaction of 1O2 with free dGp. Reaction of 1O2 with ss or ds M13mp10 DNA
      led to biological inactivation of these DNAs, ss DNA being at least 100-fold more
      sensitive than ds DNA. It could be concluded that inactivation of the ss DNA must
      be largely due to 1O2-induced DNA lesions other than 8-oxo-dG. In agreement with
      the observed preferential reaction of 1O2 with dG most of the so far sequenced
      mutations, induced by 1O2 in a 144 bp mutation target sequence inserted in the
      lacZ alpha gene of ss or ds M13mp10 DNA, occurred at a G or G/C base pair
      respectively. A preference for G(C) to T(A) transversions can be observed for
      which 8-oxo-dG might have been responsible. In ss DNA a significant number of the
      mutations are characterized by the fact that a G is deleted.

PMID- 1383779
TI  - Hypothesis: a damaging role in aging for reactive protein oxidation products?
AB  - This paper discusses our knowledge of protein oxidation and its relationship to
      aging. It also outlines new observations from our laboratories concerning
      reactive species produced during protein oxidation, and proposes that these may
      inflict damage on other molecules, and hence contribute to the progression of
      aging. Whereas it has previously been difficult to see how relatively inert
      protein oxidation products could possibly have any causal role in aging, the
      detection of these novel reactive species implies a potentially significant role.

PMID- 1383780
TI  - A novel hypothesis of lipofuscinogenesis and cellular aging based on interactions
      between oxidative stress and autophagocytosis.
AB  - Based on a series of experiments, using cultured postmitotic neonatal rat cardiac
      myocytes as a model system, we present a novel hypothesis of lipofuscin
      formation. This hypothesis proposes that lipofuscin is formed within secondary
      lysosomes due to an interplay of two processes, the production of partially
      reduced oxygen species by mitochondria and the autophagocytotic degradation
      within secondary lysosomes. Specifically, it is proposed that H2O2 generated by
      mitochondria and other organelles permeates into the lumen of secondary
      lysosomes, which contain iron derived from cellular structures undergoing
      intralysosomal degradation. The interaction between reactive ferrous iron and
      H2O2 results, via Fenton-type mechanisms, in the generation of hydroxyl free
      radicals (OH), inducing lipid peroxidation and eventually leading to
      intermolecular cross-linking and lipofuscin formation. Additionally, mitochondria
      undergoing intralysosomal decomposition might continue for a certain period to
      produce superoxide anion radicals (O2-) and thus also H2O2. This model of
      lipofuscinogenesis could satisfactorily explain the variations observed in the
      rates of lipofuscinogenesis among different postmitotic cell types in various
      species. Such variations might arise from a variety of factors including
      differences in the efficiency of the 'anti-oxidative shield', rate of H2O2
      generation, amount of chain-breaking antioxidants, mode of intralysosomal iron
      chelation, rate of autophagocytosis as well as degree of efficiency of the
      intralysosomal hydrolytic enzymes.

PMID- 1383781
TI  - Cell culture models for oxidative stress: superoxide and hydrogen peroxide versus
      normobaric hyperoxia.
AB  - According to the free radical theory of aging, loss of cellular function during
      aging is a consequence of accumulating subcellular damage inflicted by activated
      oxygen species. In cells, the deleterious effects of activated oxygen species may
      become manifest when the balance between radical formation and destruction
      (removal) is disturbed creating a situation denoted as 'oxidative stress'. Cell
      culture systems are especially useful to study the effects of oxidative stress,
      in terms of both toxicity and cellular adaptive responses. A better understanding
      of such processes may be pertinent to fully comprehend the cellular aging
      process. This article reviews three model systems for oxidative stress:
      extracellular sources of O2-. and H2O2, and normobaric hyperoxia (elevated
      ambient oxygen). Methodological and practical aspects of these exposure models
      are discussed, as well as their prominent effects as observed in cultures of
      Chinese hamster cell lines. Since chronic exposure models are to be preferred, it
      is argued that normobaric hyperoxia is a particularly relevant oxidative stress
      model for in vitro cellular aging studies.

PMID- 1383782
TI  - Genotoxic activity of three carcinogens in peripheral blood erythrocytes of the
      newt Pleurodeles waltl.

PMID- 1383783
TI  - Precise excision of transposons and point mutations induced by chemicals.
AB  - The ability of 23 chemicals (carcinogens and non-carcinogens) to induce precise
      excision of Tn10 and point mutations was studied in experiments with a single
      strain. The mutation assay was shown to detect a wider spectrum of genotoxic
      agents than the assay of Tn10 precise excision. The latter was induced only by
      potent SOS mutagens, which is in accordance with data on the SOS dependence of
      the induction of precise excision of Tn10. The precise excision assay as an
      additional test contributing to the knowledge of particular features of the
      action of a tested mutagen is discussed. The induction of precise excision of
      Tn10 by pyrene (and its failure to induce point mutations in this strain)
      demonstrates the value of using the transposon excision assay in cases of
      'problem' mutagens.

PMID- 1383784
TI  - The value of cytogenetic monitoring versus film dosimetry in the hot zone of a
      nuclear power plant.
AB  - Cytogenetic analysis was carried out in 41 workers prior to and following regular
      maintenance work in a nuclear power plant. Although film dosimetry did not show
      the maximal annual permitted dose in any of the examined subjects, cytogenetic
      analysis carried out following the work detected dicentric chromosomes in
      peripheral blood lymphocytes of 20 workers. According to our findings smoking
      habits and previous exposure to ionizing radiation had no effect on the increased
      number of chromosomal aberrations.

PMID- 1383785
TI  - Proliferation index in bone marrow cells from severely malnourished rats during
      lactation.
AB  - The aim of this study was to determine if severe malnutrition affects the
      proportion of proliferating bone marrow cells in malnourished rats during
      lactation. Sister chromatid staining of metaphases was used as a parameter, as
      well as the morphology, size and color of bromodeoxyuridine labeled interphase
      nuclei. The BrdU proliferation labeling index was statistically lower in
      malnourished rats (20.4%), than in well-nourished controls (35.1%). A difference
      was also found between the two groups in the proportion of metaphases in first,
      second and third or successive cell cycle. The average generation time was longer
      in the malnourished group: 15.3 h, against 11.8 h for the controls. These results
      indicate that severe malnutrition affects both the proportion of bone marrow
      proliferating cells and their cell kinetics.

PMID- 1383786
TI  - Interactive cytogenetic effects on rat bone-marrow due to chronic ingestion of
      2,5,2',5' and 3,4,3',4' PCBs.
AB  - Rats who were fed low doses of single PCBs, either 2,5,2',5' or 3,4,3',4', did
      not demonstrate any chromosome breakage or mitotic changes in their bone marrow
      cells. However, there was a significant increase in chromosome damage observed in
      bone marrow cells of rats ingesting 10 ppm 2,5,2',5' plus 0.1 ppm 3,3,3',4' in
      combination. It is suggested that this PCB combination, previously found to cause
      superadditive chromosome damage in vitro, is also capable of causing chromosome
      damage in vivo, but these effects do not compromise cell proliferation because
      the mitotic index is not depressed.

PMID- 1383787
TI  - Reevaluation of the induction of specific-locus mutations in spermatogonia of the
      mouse by acrylamide.

PMID- 1383788
TI  - Differences in sister-chromatid exchange frequency between homologous chromosomes
      in Muntiacus muntjak.
AB  - The frequency of sister-chromatid exchanges (SCEs) on homologous autosomes was
      studied in the peripheral blood lymphocytes of the Indian muntjac. The homologous
      autosomes differed from one another with respect to the SCE frequency on them.

PMID- 1383789
TI  - Cytogenetic monitoring of farm animals under conditions of environmental
      pollution.
AB  - Cytogenetic examinations were carried out in 13 cattle farms, two herds of
      horses, one stag farm and 13 pig farms in areas with different levels of
      environmental contamination. The frequency of aberrant cells per 100 mitoses was
      3.67 +/- 1.89 in pigs (n = 260) and 4.16 +/- 2.4 in herbivores (n = 497). This is
      a significant difference (p < 0.01). Ten times higher frequencies of chromatid
      exchanges were found in pigs. The examined herds were classified into three
      groups by the level of environmental contamination (satisfactory, impaired and
      severely impaired environment). Significant differences in aberrant cell counts
      were recorded between the groups of herbivorous animals. Significant differences
      in pigs were recorded only between herds in satisfactory and severely impaired
      environments. Significantly higher frequencies of aberrant cells were found in
      farms of herbivorous animals in the industrial area of Pardubice compared with
      findings in the South Moravian agricultural area (4.7% and 3.1% respectively).
      The effect of local contamination sources on farm environment was also
      investigated. A cattle farm located in the vicinity of a large chemical plant was
      examined five times at 6-month intervals. An autumn examination revealed
      significantly higher frequencies of aberrant cells compared with the spring
      examination.

PMID- 1383791
TI  - Cytogenetic effects of sodium azide encapsulated in liposomes on heteroploid cell
      cultures.
AB  - Lipid vesicles (liposomes) have been shown to be a useful vehicle for the
      delivery of a variety of compounds to cultured cells. Using multilamellar
      vesicles (MLV) and small unilamellar vesicles (SUV) we were able to deliver the
      classical mutagen, sodium azide, into human heteroploid HEp-2 cells. With this
      method sodium azide is not diluted in culture medium, but it is 'focused' into
      cells, producing chromosomal aberrations and other major genetic damages. Our
      results indicate that liposomes are suitable vectors for introducing clastogenic
      substances into cultured human cells.

PMID- 1383790
TI  - Potentiation of sodium chromate(VI)-induced chromosomal aberrations and mutation
      by vitamin B2 in Chinese hamster V79 cells.
AB  - The effect of vitamin B2, which is capable of reducing chromium(VI) to
      chromium(V), on chromosomal aberrations and mutation caused by Na2CrO4 was
      investigated in Chinese hamster V79 cells. Pretreatment with 200 microM vitamin
      B2 (riboflavin) for 24 h prior to exposure to Na2CrO4 (2.5-5 microM) resulted in
      an increase of metal-induced chromosomal aberrations and mutation at the HGPRT
      locus. These and other previous studies suggest that vitamin B2 enhances the
      clastogenic and mutagenic action of chromate compounds, through its ability to
      directly reduce chromium(VI) in cells.

PMID- 1383793
TI  - Sleep deprivation in human males and its effect on SCE rates in chromosomes--a
      preliminary study.
AB  - The present preliminary study on 5 healthy volunteers deprived of sleep for a day
      showed a considerable increase in sister-chromatid exchange (SCE) rate in the
      chromosomes after sleep deprivation. Although the rate of increase varied between
      the studied subjects, interestingly the 5% plasma from a volunteer with a
      statistically significant increase after sleep deprivation, when supplemented to
      cell cultures from an age-matched normal subject, induced high SCEs. This
      suggests the presence/absence of some factor(s) in plasma samples of subjects
      showing high SCEs after sleep deprivation, playing a role in the induction of
      high SCEs in normal cells exposed to the samples in vitro. The present study also
      suggests that there could be categories which may or may not respond to sleep
      deprivation with high SCE induction and their plasma supplemented to normal cell
      culture in turn may or may not induce high SCEs. Nevertheless, the
      pathophysiological role of high SCEs induced by sleep deprivation in some cases
      remains intriguing and unresolved and needs further extensive study.

PMID- 1383792
TI  - Chromosome analysis in a population living in an area of Germany with the highest
      fallout deposition from the Chernobyl accident.
AB  - Chromosome analyses were carried out in 1989 in peripheral lymphocytes of 30
      persons from the region in southeast Bavaria (Berchtesgaden) that received the
      highest radiocesium deposition (> 42 kBq/m2) in Germany. These persons belonged
      to a group for whom body burdens of radiocesium had been surveyed in 1987.
      Chromosome analyses had been performed by Stephan and Oestreicher for members of
      the same group in the period 1987-1990, and these authors have reported elevated
      rates of chromosome aberrations. Pohl-Ruling et al. (1991) have, likewise,
      concluded that there have been increased rates of chromosome aberrations in the
      population of the nearby Salzburg region in 1987. In the study reported here we
      do not see any elevations compared to our large pre-Chernobyl control group. The
      difference between our findings and the report of earlier increases cannot be
      fully explained in terms of the known temporal decrease of the rate of dicentrics
      and ring chromosomes.

PMID- 1383794
TI  - Sister-chromatid exchanges are increased in epileptics, but not by sodium
      valproate.
AB  - Sister-chromatid exchange (SCE) frequency has been studied from peripheral blood
      lymphocyte cultures of 21 patients with epilepsy on sodium valproate, 20 patients
      who had not started therapy (untreated) and 20 normal healthy controls. Treated
      and untreated patients with epilepsy were observed to have higher SCE frequencies
      (mean 9.05 and 9.82 respectively) than healthy controls (mean 4.8; P < 0.001).
      There was no significant difference in SCE frequency between treated and
      untreated patients. This suggests that the disease itself may be associated with
      an increased frequency of SCEs.

PMID- 1383795
TI  - Spontaneous and induced levels of chromosomal aberration and sister-chromatid
      exchange in neurofibromatosis: no evidence of chromosomal hypersensitivity.
AB  - Chromosomal aberration (CA) and sister-chromatid exchange (SCE) frequencies have
      been assessed in 9 patients with von Recklinghausen's neurofibromatosis (NF1) and
      8 apparently healthy controls. In separate experiments over a 5-year period,
      blood lymphocytes, skin fibroblast cell strains, and lymphoblastoid lines from
      both groups were treated with X-rays or mitomycin C (MMC) to determine whether
      the NF1 group was more sensitive to these agents than the control group. No
      difference between cells from NF1 patients and controls was observed with respect
      to spontaneous or X-ray-induced CA. Spontaneous or X-ray- and MMC-induced SCE
      frequencies were also similar in NF1 patients and controls.

PMID- 1383796
TI  - Inducible protective processes in animal systems. III. Adaptive response of
      meiotic cells of the grasshopper, Poecilocerus pictus, to a low dose of ethyl
      methanesulfonate.
AB  - Meiotic cells of Poecilocerus pictus exposed to a low dose of 0.03 M of ethyl
      methanesulfonate (EMS) were found to be resistant to the induction of chromosomal
      anomalies by a subsequent challenge dose (0.12 M) of the same mutagen as compared
      to cells that were not pre-exposed. They responded with a significantly reduced
      incidence of chromosomal anomalies in metaphase I and II and anaphase I and II.
      These results indicate the presence of an inducible chromosomal repair mechanism
      in meiotic cells of P. pictus. The incidence of chromosome damage was found to be
      less when the time lag between the conditioning and challenging doses was
      reduced, suggesting that under the conditions tested, the efficacy of repair
      enzymes gradually decreases as the time between the two doses increases.

PMID- 1383797
TI  - Sex differences in micronucleus induction with hycanthone methanesulfonate in
      bone marrow cells of mice.
AB  - The clastogenic effect of the antischistosomal drug hycanthone methanesulfonate
      was studied with the micronucleus test in mouse bone marrow cells. Male and
      female (102/El x C3H/El)F1 mice were treated with single i.p. injections. Bone
      marrow was sampled 18, 24 and 30 h after treatment with 100 mg/kg. The highest
      micronucleus yield occurred at 24 h. The dose response for micronucleus induction
      at 24 h after treatment was non-linear for doses between 5 and 300 mg/kg. The
      lowest effective dose was 5 mg/kg for females and 10 mg/kg for males. The
      experiments revealed a significantly higher sensitivity of female mice for the
      induction of micronuclei in polychromatic erythrocytes by hycanthone
      methanesulfonate. This result supports the recommendation to use both sexes for
      quantitative assessment of genotoxicity in the micronucleus test.

PMID- 1383798
TI  - Large deletions are tolerated at the hprt locus of in vivo derived human T
      lymphocytes.
AB  - A cloning assay was used to recover hprt- T-lymphocytes from adult human males.
      Analysis of crude cellular extracts by polymerase chain reactions (PCRs)
      demonstrated that 7% (16/218) of the hprt mutations were due to total deletion of
      the hprt gene. 14 of the 16 mutants were examined by PCR for the presence of
      flanking DNA to determine the extent of the deletions. The deletion mutation in
      13 mutants was at least 350 kb with 5 of these deletions being at least 700 kb.
      The largest deletions were greater than 15 times the size of the hprt gene.
      Therefore, large deletions are tolerated at the hprt locus of human T
      lymphocytes.

PMID- 1383799
TI  - Detection of gamma-ray-induced DNA damages in malformed dominant lethal embryos
      of the Japanese medaka (Oryzias latipes) using AP-PCR fingerprinting.
AB  - Adult male fish of the medaka HNI strain exposed to 9.5 Gy or 19 Gy (0.95 Gy/min)
      of gamma-rays were mated with non-irradiated female fish of the Hd-rR strain.
      Genomic DNA was prepared from malformed individual embryos which were expected to
      be dominant lethal and used for AP-PCR fingerprinting. By the use of a part of
      the T3 promoter sequence (20 mer), which, to our knowledge, is not found in the
      medaka genome as an arbitrary primer, we found polymorphisms in genomic
      fingerprints which could distinguish the parental strains. On the other hand, we
      found that the fingerprints of F1 hybrids were the sum of those of their parents.
      Based on these findings, we analyzed the fingerprints of genomic DNA of each
      severely malformed embryo, because we expect that radiation-induced genomic
      damages resulting in severe malformation and eventually in dominant lethals
      should be detected as changes in paternal fingerprints of F1 hybrids. Indeed, we
      succeeded in detecting changes in genomic DNA as loss of some paternal bands in
      fingerprints of malformed embryos. One of 10 malformed embryos obtained from 9.5
      Gy gamma-irradiated males had lost one band of the paternal origin and 4 of 12
      malformed embryos obtained from 19 Gy gamma-irradiated males had lost 5 bands.
      These results indicated a possibility that quantitative as well as qualitative
      estimation of gamma-ray-induced DNA damages can be made by this method which does
      not require the functional selection based on a specific target gene.

PMID- 1383800
TI  - An enhancement of the yield of X-ray-induced Minute mutations in the c3G female
      ywmf-2 male system of Drosophila melanogaster.
AB  - The possible enhancement of the yield of X-ray-induced Minute mutations in the
      c3G female-ywmf-2 male system which is proposed to be responsible for the high
      production of spontaneous Minute mutations was investigated. To determine and
      compare the yield of X-ray-induced Minute mutations exactly, four series of
      crosses were made: (a) ywmf-2 male x Oregon-R (OrR) female crosses, spontaneous
      Minute mutations were scored; (b) ywmf-2 male x c3G female crosses, spontaneous
      Minute mutations produced in the c3G female-ywmf-2 male system were evaluated;
      (c) X-irradiated ywmf-2 male x OrR female crosses, the yield of Minutes induced
      by X-rays in the different stages of male germ cells was evaluated; and (d) X
      irradiated ywmf-2 male x c3G female crosses, the yield of X-ray-induced Minutes
      in the c3G female-ywmf-2 male system was evaluated. The results show that the
      yield of X-ray-induced Minutes recorded in the c3G female-ywmf-2 male system is
      2.37-16.55 times more than that in the ywmf-2 male x OrR female crosses. This
      finding clearly indicates that the yield of these mutations is greatly enhanced
      in the c3G female-ywmf-2 male system. This possibly suggests that the c3G female
      ywmf-2 male system may be responsible not only for the high production of
      spontaneous Minute mutations but also for the high formation of radiation-induced
      Minutes.

PMID- 1383801
TI  - Effect of 60-Hz magnetic fields on ultraviolet light-induced mutation and mitotic
      recombination in Saccharomyces cerevisiae.
AB  - The purpose of this study was to examine the effect of extremely low frequency
      (ELF) magnetic fields on the induction of genetic damage. In general, mutational
      studies involving ELF magnetic fields have proven negative. However, studies
      examining sister-chromatid exchange and chromosome aberrations have yielded
      conflicting results. In this study, we have examined whether 60-Hz magnetic
      fields are capable of inducing mutation or mitotic recombination in the yeast
      Saccharomyces cerevisiae. In addition we determined whether magnetic fields were
      capable of altering the genetic response of S. cerevisiae to UV (254 nm). We
      measured the frequencies of induced mutation, gene conversion and reciprocal
      mitotic crossing-over for exposures to magnetic fields alone (1 mT) or in
      combination with various UV exposures (2-50 J/m2). These experiments were
      performed using a repair-proficient strain (RAD+), as well as a strain of yeast
      (rad3) which is incapable of excising UV-induced thymine dimers. Magnetic field
      exposures did not induce mutation, gene conversion or reciprocal mitotic crossing
      over in either of these strains, nor did the fields influence the frequencies of
      UV-induced genetic events.

PMID- 1383802
TI  - Toxicity of some heavy metals in vivo and in vitro in Helianthus annuus.
AB  - To compare the toxicity of some heavy metals in vivo and in vitro, the effects of
      six metals, aluminum (Al), cadmium (Cd), copper (Cu), nickel (Ni), lead (Pb), and
      zinc (Zn) were studied in the oil-yielding plant Helianthus annuus. The
      percentage of seed germination and cytotoxic effects at different concentrations
      and durations of treatment as well as the growth rate of callus tissues in vitro
      were compared to ascertain the concentrations that can either support plant
      growth or cause lethality. Highest toxicity to the plant system was observed from
      the effects of Pb both at high and low concentrations whereas Zn was the least
      toxic; and similar effects were seen in vivo and in vitro. The clastogenic
      effects of Al, Cd, Cu, and Ni were dependent on concentration and length of
      treatment. Cu and Zn showed less severe cytotoxic damages than Al, Cd, Pb, and
      Ni. In vitro growth could be supported at 100-1000 times the diluted
      concentrations of the metals in comparison to in vivo treatment.

PMID- 1383803
TI  - Detection of oxidative mutagens in an urban air-particulate extract: a
      preliminary study.
AB  - The Ames assays strains TA98 and TA100 have been useful in characterizing complex
      mixtures from organic solvent extracts of particles from diesel-powered vehicles,
      ambient air, and other sources. In this paper we report preliminary experiments
      using TA102, a bacterial strain that detects compounds that can oxidize DNA, to
      characterize the mutagenicity of an ambient air sample collected in Ann Arbor,
      MI. Four sets of ambient air filters were collected in duplicate over a period of
      several days. The mutagenicities of methylene chloride extracts of these filters
      were compared using strains TA98, TA100 and TA102. The concentration-mutagenicity
      data for TA98 and TA100 were linear over the concentration range 0-200 micrograms
      extract/plate. The mutagenicity of the extracts using TA102 was much lower than
      the other two strains and was non-linear over the concentration range tested.
      These results suggest that it would be difficult to use TA102 to identify the
      oxidative mutagens present in an ambient air particulate extract.

PMID- 1383804
TI  - The lipid peroxidation product 4-hydroxynonenal is a potent inducer of the SOS
      response.
AB  - An important aspect of bacterial mutagenesis by several difunctional carbonyl
      compounds appears to be the induction of the SOS system. We tested the ability of
      a series of carbonyl compounds to induce expression of the SOS-regulated umu
      operon in Salmonella typhimurium TA1535/pSK1002. SOS-inducing potencies varied
      widely among the carbonyl compounds tested. 4-Hydroxynonenal, a product of lipid
      peroxidation, was the most potent SOS-inducer, with maximal induction observed at
      concentrations of 0.1-1 microM. Acrolein, crotonaldehyde and methacrolein induced
      little increase over background umu expression. Malondialdehyde, another product
      of lipid peroxidation, was a very weak SOS-inducer with a maximal response
      induced at a concentration of 28 mM. Substitution at the alpha-position of
      malondialdehyde, which abolishes frameshift mutagenicity, did not abolish SOS
      inducing activity. Substitution of the hydroxyl group of malondialdehyde and
      alpha-methyl-malondialdehyde by a better leaving group (benzoyloxy) resulted in
      an approximately 250-fold higher SOS-inducing potency. Comparison of the present
      results to literature reports on bacterial mutagenicity indicates a poor
      correlation of the two properties between different classes of difunctional
      carbonyl compounds and even within the same class of difunctional carbonyl
      compounds.

PMID- 1383805
TI  - DNA repair.

PMID- 1383806
TI  - Neither enhanced removal of cyclobutane pyrimidine dimers nor strand-specific
      repair is found after transcription induction of the beta 3-tubulin gene in a
      Drosophila embryonic cell line Kc.
AB  - Nucleotide excision repair (NER) of ultraviolet (UV) light induced cyclobutane
      pyrimidine dimers (CPDs) was assayed in a Drosophila melanogaster Kc subline that
      responds to treatment with the steroid hormone 20-hydroxyecdysone (20-OH-E; beta
      ecdysone, ecdysterone). In this cell line the hormone induces transcription of
      the beta 3-tubulin gene which is not expressed under standard culture conditions.
      Cells were exposed to either 10 or 15 J/m2 UV (predominantly 254-nm) and removal
      of CPDs from several genes, including beta 3-tubulin, and total cellular DNA was
      assayed. We show that upon induction of transcription of the beta 3-tubulin gene,
      its repair is not enhanced. In non-treated as well as 20-OH-E treated cells,
      repair kinetics in beta 3-tubulin resemble those in the active genes Gart and
      Notch, the inactive locus white and total cellular DNA. Moreover, in the presence
      as well as in the absence of transcription, the separate strands of the beta 3
      tubulin gene are repaired with the same rate and to the same extent: about 90%
      after 24 h. It can be concluded from these observations that transcription is not
      a prerequisite for the efficient repair of CPDs in the Drosophila embryonic Kc
      cell line.

PMID- 1383807
TI  - Relationship between the functional regions of the RecA protein and ATP
      hydrolysis in UV-irradiated Escherichia coli cells.
AB  - The time course of the intracellular ATP concentration in several UV-irradiated
      RecA protease constitutive (Cptc) mutants of E. coli has been studied. All Cptc
      mutants harboring a mutation in region 3 of the RecA protein (including amino
      acid residues 298-301) increased ATP after UV damage but without any subsequent
      decrease. Nevertheless, these mutants induced the SOS response after UV
      irradiation. Likewise, truncated RecA proteins lacking region 3 are also unable
      to carry out massive ATP hydrolysis in UV-irradiated cells. On the other hand,
      mutants in region 1 (including amino acids 25-39) or 2 (amino acids 157-184) of
      the RecA protein showed an increase in ATP concentration during the first 20 min
      following UV irradiation, which dropped afterwards to the basal level. All these
      data indicate that region 3 of the RecA protein must be involved in the ATP
      hydrolysis process. Furthermore, a relationship between the quantity of the UV
      mediated ATP produced and the strength of the different RecA Cptc mutants has
      also been found. Accordingly, both lexA71::Tn5 and null lexA mutants of E. coli
      only show a cellular ATP increase after UV irradiation when containing a
      multicopy plasmid carrying either a wild-type lexA or a lexA (Ind-) gene.

PMID- 1383808
TI  - Suppression of X-ray-induced chromosome aberrations in ataxia telangiectasia
      cells by introduction of a normal human chromosome 11.
AB  - We studied X-ray-induced chromosome aberrations in ataxia telangiectasia (AT)
      cells containing an introduced chromosome 11 or 12 derived from normal human
      fibroblasts. We used microcell-mediated chromosome transfer to introduce the
      normal chromosomes into AT cells belonging to complementation group D. Cells were
      irradiated with 1 Gy of X-rays in the G2 phase. All 5 hybrid clones with an
      introduced chromosome 11 showed a reduction in the frequency of chromatid-type
      aberrations to normal levels, whereas all 4 hybrid clones with an introduced
      chromosome 12 failed to show this reduction. This finding, taken together with
      our previous report that chromosome 11 can restore radioresistant cell killing in
      AT cells, indicates that a defective gene on chromosome 11 in AT cells is
      responsible for the hypersensitivity to not only cell killing but also chromosome
      aberrations. Our results suggest that a putative AT gene on chromosome 11 plays
      an important role in the repair process of radiation-induced DNA damage that
      leads to chromosome aberrations.

PMID- 1383809
TI  - Repair of X-ray induced DNA strand damage by isolated rat splenic lymphocytes.
AB  - Although a number of chemicals can alter DNA repair function, little is known
      about the effect of chronic, low dose exposure to environmental agents on DNA
      repair capacity. Lymphocytes provide a potential target population to study the
      effects of chronic exposures to low doses of toxic chemicals since they are an
      easily obtainable cell population. Prior to investigating the repair capacity of
      chemically exposed lymphocytes, the repair by chemically naive lymphocytes has
      been characterized. In the present study, the DNA repair capacity of isolated rat
      lymphocytes was characterized. The capacity of these cells to repair single
      strand DNA breaks (SSB) was determined after in vitro treatments with X-rays. The
      effect of in vitro exposure to 3-aminobenzamide (3-AB) on DNA repair capacity was
      also assessed. The levels of induced SSB and their repair were determined using
      the alkaline elution technique. Splenic lymphocytes were isolated and placed in
      culture medium 18 h prior to assessment of repair capacity, but were not
      stimulated with mitogens. A dose-dependent increase in SSB was observed following
      exposure of lymphocytes to 300 or 600 rad. The rate of SSB repair was analyzed
      after a dose of 400 rad. Approximately 80% of the DNA strand break repair was
      completed within 60 min. The half-time for repair of these lesions by lymphocytes
      was determined to be 21.3 min. Exposure to 3-AB resulted in a decrease in the
      rate of repair of the X-ray-induced strand breakage. Although no SSB were
      detected at the end of a 1-h 3-AB treatment of non-irradiated cells, significant
      accumulation of SSB was observed after a 2-h treatment. The characterization of
      DNA repair in rat lymphocytes following in vitro exposure to X-rays will allow us
      to investigate the effects of chronic, in vivo toxicant exposure on the capacity
      of isolated lymphocytes to repair DNA damage produced by X-rays.

PMID- 1383810
TI  - Abnormal processing of transfected plasmid DNA in cells from patients with ataxia
      telangiectasia.
AB  - In order to assess spontaneous mutability and accuracy of DNA joining in ataxia
      telangiectasia, a disorder with spontaneous chromosome breakage, the replicating
      shuttle vector plasmid, pZ189, was transfected into SV40 virus-transformed
      fibroblasts from ataxia telangiectasia patients. The ataxia telangiectasia
      fibroblasts showed elevated frequency of micronuclei, a measure of chromosome
      breakage. The spontaneous mutation frequency was normal with circular plasmids
      passed through the ataxia telangiectasia line. These results were compared to
      those with transformed fibroblasts from a patient with xeroderma pigmentosum, and
      from a normal donor. Mutation analysis revealed spontaneous point mutations and
      deletions in the plasmids with all 3 cell lines, however, insertions or complex
      mutations were only detectable with the ataxia telangiectasia line. To assess DNA
      joining ability, linear plasmids which require joining of the DNA ends by host
      cell enzymes for survival, were transfected into the cells. We found a 2.4-fold
      less efficient DNA joining in ataxia telangiectasia fibroblasts (p = 0.04) and a
      2.0-fold higher mutation frequency (p less than 0.01) in the recircularized
      plasmids than with the normal line. Plasmid DNA joining and mutation frequency
      were normal with the xeroderma pigmentosum fibroblasts. These findings with the
      ataxia telangiectasia fibroblasts of abnormal types of spontaneous mutations in
      the transfected plasmid and inefficient, error-prone DNA joining may be related
      to the increased chromosome breakage in these cells. In contrast, an EB virus
      transformed ataxia telangiectasia lymphoblast line with normal frequency of
      micronuclei showed normal types of spontaneous mutations in the transfected
      plasmid and normal frequency of DNA joining which was error-prone. These data
      indicate that mechanisms that produce chromosome breakage in ataxia
      telangiectasia cells can be reflected in processing of plasmid vectors.

PMID- 1383811
TI  - A re-examination of the intragenome distribution of repaired sites in
      proliferating xeroderma pigmentosum complementation group C fibroblasts.
AB  - We find that rapidly proliferating fibroblasts from xeroderma pigmentosum
      complementation group C (XP-C) patients, cells that have a small residual DNA
      excision repair capacity, repair DNA in localized regions of the genome in a
      clustered pattern rather than at single sites in dispersed locations. This
      finding is similar to that observed earlier for nondividing cells but is in
      contrast to published results that indicate that the residual repair in
      proliferating XP-C cells is dispersed throughout the genome in a non-clustered
      pattern. While we detect the same amount of repair in both proliferating and
      nondividing cells, we also observe no shift from the clustered pattern of repair
      to a more dispersive pattern when nondividing cells are stimulated to proliferate
      by fresh serum addition. We have no obvious explanation for these discrepancies
      with the published results. We have noted previously that proliferating XP-C
      cells are very UV sensitive relative to normal cells while nondividing cells that
      exhibit the same amount of repair activity are relatively UV resistant. There is
      no satisfactory explanation for this change in relative response to the lethal
      effects of UV, a change not observed for cell strains from other XP
      complementation groups. However, we argue that clustered repair in specific
      genomic regions promotes survival in nondividing XP-C cells but does not promote
      survival in proliferating cells.

PMID- 1383812
TI  - New DNA repair-deficient mutants of Chlamydomonas reinhardtii.
AB  - Two new UV-sensitive mutants of Chlamydomonas reinhardtii, uvs12 and uvs13, were
      characterized. Genetic analysis proved that they were non-allelic. They
      complemented the other repair-deficient mutants uvs8, uvs9, uvs10 and uvs11.
      While uvs12 may have an impaired excision-repair pathway, uvs13 is, by its UV
      sensitivity under non-photoreactivating conditions, very similar to uvsE1 and
      uvs10, but differs in the effect of caffeine on its survival. After UV, survival
      of some repair-deficient mutants was, under photoreactivating conditions, much
      lower than that of phr1, while survival of other repair-deficient mutants did not
      differ from that of a wild-type strain. A lower UV survival of some dark-repair
      defective mutants of Chlamydomonas reinhardtii, under photoreactivating
      conditions, can perhaps be used as an additional criterion for mutants defective
      in the excision-repair pathway.

PMID- 1383813
TI  - Inhibition of DNA polymerase activity by thymine hydrates.
AB  - Ultraviolet irradiation of DNA results in various pyrimidine modifications. We
      have demonstrated formation of both cis-thymine hydrate and trans-thymine hydrate
      (6-hydroxy-5,6-dihydrothymine) in UV-irradiated poly(dA-dT):poly(dA-dT). Both are
      released from DNA as free bases by bacterial and human glycosylases. Thymine
      hydrates are stable in DNA and can be detected in control, unirradiated
      substrates. We examined the effects of thymine hydrates in UV-irradiated
      substrate poly(dA-dT):poly(dA-dT) on E. coli DNA polymerase I activity. Enzymic
      incorporation of labeled thymidine-5'-monophosphate significantly decreased with
      increasing UV dose. Reversal of DNA thymine hydrates to thymines by mild heating
      of the substrate prior to enzymic reaction resulted in partial recovery of
      nucleotide incorporation. Cyclobutane thymine dimers are formed between non
      adjacent thymines in UV-irradiated poly(dA-dT):poly(dA-dT). These are responsible
      for the incomplete recovery of DNA polymerase activity following heating due to
      their heat stability. Analyses of the irradiated and hydrolyzed substrate also
      demonstrated formation of minor yields of photoproducts formed by covalent
      linkage of adjacent thymines and adenines by UV-irradiation. Therefore, the
      thymine hydrates formed in UV-irradiated DNA partially inhibit polymerase
      activity during DNA synthesis and thus could be potentially lethal if unrepaired.

PMID- 1383814
TI  - Recent advances in DNA repair and mutation: a report of the meeting of the
      British Photobiology Society and the DNA Repair Network.
AB  - The 1991 joint meeting of the British Photobiology Society and the DNA Repair
      Network was held in London on the 16th of December at the Polytechnic of East
      London. Despite the best efforts of the IRA to disrupt transport in London, a
      full programme of eighteen talks were presented on the theme of "Recent Advances
      in DNA Repair and Mutation".

PMID- 1383815
TI  - Inorganic mercury is transported from muscular nerve terminals to spinal and
      brainstem motoneurons.
AB  - The distribution of mercury within the brainstem and spinal cord of mice was
      investigated with the autometallographic technique after intramuscular
      administration of a single dose of mercuric mercury (HgCl2). Deposits of mercury
      were localized to motor neurons of the spinal cord and to brainstem motor nuclei;
      i.e., neurons with their peripheral projections outside the blood-brain barrier.
      Unilateral ligation of the hypoglossal nerve prior to the injection of HgCl2
      prevented the accumulation of mercury deposits in the ipsilateral hypoglossal
      nucleus. The selective accumulation of mercury in spinal and brainstem
      motoneurons is most probably due to a leakage of metal-protein complexes from
      capillaries in muscle into myoneural junctions, followed by uptake into nerve
      terminals and retrograde axonal transport. The possible link between this process
      and the development of motor neuron degeneration in ALS is discussed.

PMID- 1383817
TI  - Is the prostate pill finally here?

PMID- 1383816
TI  - The effect of finasteride in men with benign prostatic hyperplasia. The
      Finasteride Study Group.
AB  - BACKGROUND: Benign prostatic hyperplasia is a progressive, androgen-dependent
      disease resulting in enlargement of the prostate gland and urinary obstruction.
      Preventing the conversion of testosterone to its tissue-active form,
      dihydrotestosterone, by inhibiting the enzyme 5 alpha-reductase could decrease
      the action of androgens in their target tissues; in the prostate the result might
      be a decrease in prostatic hyperplasia and therefore in symptoms of urinary
      obstruction. METHODS: In a double-blind study, we evaluated the effect of two
      doses of finasteride (1 mg and 5 mg) and placebo, each given once daily for 12
      months, in 895 men with prostatic hyperplasia. Urinary symptoms, urinary flow,
      prostatic volume, and serum concentrations of dihydrotestosterone and prostate
      specific antigen were determined periodically during the treatment period.
      RESULTS: As compared with the men in the placebo group, the men treated with 5 mg
      of finasteride per day had a significant decrease in total urinary-symptom scores
      (P less than 0.001), an increase of 1.6 ml per second (22 percent, P less than
      0.001) in the maximal urinary-flow rate, and a 19 percent decrease in prostatic
      volume (P less than 0.001). The men treated with 1 mg of finasteride per day did
      not have a significant decrease in total urinary-symptom scores, but had an
      increase of 1.4 ml per second (23 percent) in the maximal urinary-flow rate, and
      an 18 percent decrease in prostatic volume. The men given placebo had no changes
      in total urinary-symptom scores, an increase of 0.2 ml per second (8 percent) in
      the maximal urinary-flow rate, and a 3 percent decrease in prostatic volume. The
      frequency of adverse effects in the three groups was similar, except for a higher
      incidence of decreased libido, impotence, and ejaculatory disorders in the
      finasteride-treated groups. CONCLUSIONS: The treatment of benign prostatic
      hyperplasia with 5 mg of finasteride per day results in a significant decrease in
      symptoms of obstruction, an increase in urinary flow, and a decrease in prostatic
      volume, but at a slightly increased risk of sexual dysfunction.

PMID- 1383818
TI  - Environmental exposure to lead and children's intelligence at the age of seven
      years. The Port Pirie Cohort Study.
AB  - BACKGROUND: Exposure to lead in early childhood is thought to result in delayed
      neuropsychological development. As yet there is little longitudinal evidence to
      establish whether these effects persist into later childhood. METHODS: We
      measured IQ scores in 494 seven-year-old children from the lead-smelting
      community of Port Pirie, Australia, in whom developmental deficits associated
      with elevated blood lead concentrations had already been reported at the ages of
      two and four years. Exposure to lead was estimated from the lead concentrations
      in maternal blood samples drawn antenatally and at delivery and from blood
      samples drawn from the children at birth (umbilical-cord blood), at the ages of 6
      and 15 months and 2 years, and annually thereafter. Data relating to known
      covariates of child development were collected systematically for each child
      throughout the first seven years of life. RESULTS: We found inverse relations
      between IQ at the age of seven years and both antenatal and postnatal blood lead
      concentrations. After adjustment by multiple regression for sex, parents' level
      of education, maternal age at delivery, parents' smoking status, socioeconomic
      status, quality of the home environment, maternal IQ, birth weight, birth order,
      feeding method (breast, bottle, or both), duration of breast-feeding, and whether
      the child's natural parents were living together, the relation with lead exposure
      was still evident for postnatal blood samples, particularly within the age range
      of 15 months to 4 years. For an increase in blood lead concentration from 10
      micrograms per deciliter (0.48 mumol per liter) to 30 micrograms per deciliter
      (1.45 mumol per liter), expressed as the average of the concentrations at 15
      months and 2, 3, and 4 years, the estimated reduction in the IQ of the children
      was in the range of 4.4 points (95 percent confidence interval, 2.2 to 6.6) to
      5.3 points (95 percent confidence interval, 2.8 to 7.8). This reduction
      represents an approximate deficit in IQ of 4 to 5 percent. CONCLUSIONS: Low-level
      exposure to lead during early childhood is inversely associated with
      neuropsychological development through the first seven years of life.

PMID- 1383819
TI  - Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD)
      with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma.
AB  - BACKGROUND: In 1984, the Eastern Cooperative Oncology Group began a randomized
      controlled clinical trial of patients with advanced (stage III or IV) diffuse
      mixed or diffuse large-cell lymphoma to determine whether complete-remission
      rates, survival, and toxicity differed when patients were treated with a
      chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine,
      and prednisone (CHOP), as compared with a regimen containing bleomycin,
      doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and
      leucovorin (m-BACOD). METHODS: From July 1984 through January 1988, 392 patients
      were enrolled, 325 of whom (83 percent) were eligible for the analysis and
      capable of being evaluated. The extent of disease was defined according to
      standard staging techniques, including bilateral bone-core biopsies in 88 percent
      of patients. Randomization was stratified according to age (< 60 or > or = 60
      years), performance status (0, 1, or other), stage (III or IV), and histologic
      presentation (diffuse mixed or diffuse large-cell lymphoma). RESULTS: After a
      median follow-up of four years, there were no significant differences in rates of
      complete remission, time to treatment failure, disease-free survival, or overall
      survival in the patients treated with CHOP as compared with those treated with m
      BACOD. However, there was more severe and life-threatening pulmonary, infectious,
      and hematologic toxicity associated with the m-BACOD regimen. In an attempt to
      measure the importance of dose intensity in the 325 patients who could be
      analyzed, we retrospectively calculated dose intensity (measured in milligrams
      per square meter of body-surface area per week) and normalized dose intensity
      (defined as a percentage of the prescribed dose) for all drugs. The median
      normalized dose intensity for both cyclophosphamide and doxorubicin was found to
      be greater in the patients treated with CHOP than in those treated with m-BACOD.
      CONCLUSIONS: For patients with stage III or IV diffuse mixed or diffuse large
      cell lymphoma, CHOP is superior to m-BACOD, but the role of dose intensity is not
      yet clear.

PMID- 1383820
TI  - Assisted death--a compassionate response to a medical failure.

PMID- 1383821
TI  - Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating
      with ABVD.
AB  - BACKGROUND AND METHODS: MOPP (mechlorethamine, vincristine, procarbazine, and
      prednisone) has been the standard treatment for Hodgkin's disease for almost 20
      years. In a randomized, multicenter trial, we compared three regimens of primary
      systemic therapy for newly diagnosed advanced Hodgkin's disease in Stages IIIA2,
      IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP
      alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for
      12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse
      after radiation therapy were eligible. No additional radiation therapy was given.
      Patients who did not have a complete response or who had a relapse with either
      MOPP alone or ABVD alone were switched to the opposite regimen. RESULTS: Of 361
      eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD,
      and 115 received ABVD alone. The patients were stratified according to age,
      stage, previous radiation, histologic features, and performance status. The
      overall response rate was 93 percent, with complete responses in 77 percent: 67
      percent in the MOPP group, 82 percent in the ABVD group, and 83 percent in the
      MOPP-ABVD group (P = 0.006 for the comparison of MOPP with the other two
      regimens, both of which contained doxorubicin). The rates of failure-free
      survival at five years were 50 percent for MOPP, 61 percent for ABVD, and 65
      percent for MOPP-ABVD. Age, stage (III vs. IV), and regimen influenced failure
      free survival significantly. Overall survival at five years was 66 percent for
      MOPP, 73 percent for ABVD, and 75 percent for MOPP-ABVD (P = 0.28 for the
      comparison of MOPP with the doxorubicin regimens). MOPP had more severe toxic
      effects on bone marrow than ABVD and was associated with greater reductions in
      the prescribed dose. CONCLUSIONS: In this trial, ABVD therapy for 6 to 8 months
      was as effective as 12 months of MOPP alternating with ABVD, and both were
      superior to MOPP alone in the treatment of advanced Hodgkin's disease. ABVD was
      less myelotoxic than MOPP or ABVD alternating with MOPP.

PMID- 1383822
TI  - A role for hepatitis C virus infection in type II cryoglobulinemia.
AB  - BACKGROUND: Type II cryoglobulinemia is a vasculitis characterized by
      cryoglobulins consisting of complexes of polyclonal IgG and monoclonal IgM
      rheumatoid factors. The cause of these immune complexes is unknown, though both
      the hepatitis B (HBV) and C (HCV) viruses have been suspected. METHODS: We
      studied 19 patients with Type II cryoglobulinemia for markers of HCV and HBV
      infection. Quantitative HCV antibody and RNA studies were performed on whole
      serum, cryoprecipitates, and supernatants. RESULTS: Eight patients (42 percent)
      had HCV antibodies, and 16 (84 percent) had HCV RNA: Of the 19 patients, 5 (26
      percent) had HBV markers, but only 1 had evidence of active HBV infection.
      Control serum samples from nine patients with Type I cryoglobulinemia were
      negative for HCV antibody and HCV RNA: There was a close, although not exclusive,
      association of one type of rheumatoid factor (WA) with HCV RNA: HCV antibody and
      HCV RNA were concentrated approximately 10-fold and 1000-fold, respectively, in
      the Type II cryoglobulins examined. CONCLUSIONS: Type II cryoglobulinemia is
      strongly associated with concomitant HCV infection and a high rate of false
      negative serologic tests. HCV virions and HCV antigen-antibody complexes are
      concentrated in the cryoprecipitates, most commonly in association with the WA
      type of rheumatoid factor, suggesting a role for HCV in the pathogenesis of mixed
      cryoglobulinemia.

PMID- 1383823
TI  - Cryoglobulinemia and hepatitis C virus.

PMID- 1383824
TI  - Effect of keratin on the lipid composition of Scopulariopsis brevicaulis
      (Bainier).
AB  - Lipid content and composition of Scopulariopsis brevicaulis cultured with or
      without its natural substrate keratin was investigated. Lipid content was found
      to be lower in the presence of keratin (maximum 12% against 19% in the absence of
      keratin), with differences in levels of linoleic acid (C18 = 2), palmitic (C16:0)
      and to a lesser extent palmitoleic (C16 = 1) and alpha-linolenic (C18 = 3) acids.
      The degree of unsaturation was correspondingly lower in the organisms cultured
      with keratin as substrate.

PMID- 1383825
TI  - Development of buprenorphine for the treatment of opioid dependence.
AB  - Data from these studies indicate that buprenorphine is efficacious in treating
      opioid dependence. It was possible to induct heroin addicts rapidly onto
      buprenorphine without precipitating an opioid withdrawal syndrome. A daily 8-mg
      SL dosage was sufficient to maintain individuals without producing reports of
      withdrawal symptoms. When buprenorphine was administered at the above dose every
      other day, however, mild withdrawal symptoms were reported, and responses to
      challenges with intravenously given hydromorphone appeared greater than when the
      challenges were given intramuscularly. From these results, the authors conclude
      that buprenorphine at this dose should be administered on a daily basis. These
      results are now being applied to a phase II outpatient clinical trial comparing
      buprenorphine with methadone.

PMID- 1383826
TI  - Amyloid beta-peptide is produced by cultured cells during normal metabolism.
AB  - Alzheimer's disease is characterized by the extracellular deposition in the brain
      and its blood vessels of insoluble aggregates of the amyloid beta-peptide (A
      beta), a fragment, of about 40 amino acids in length, of the integral membrane
      protein beta-amyloid precursor protein (beta-APP). The mechanism of extracellular
      accumulation of A beta in brain is unknown and no simple in vitro or in vivo
      model systems that produce extracellular A beta have been described. We report
      here the unexpected identification of the 4K (M(r) 4,000) A beta and a truncated
      form of A beta (approximately 3K) in media from cultures of primary cells and
      untransfected and beta-APP-transfected cell lines grown under normal conditions.
      These peptides were immunoprecipitated readily from culture medium by A beta
      specific antibodies and their identities confirmed by sequencing. The concept
      that pathological processes are responsible for the production of A beta must not
      be reassessed in light of the observation that A beta is produced in soluble form
      in vitro and in vivo during normal cellular metabolism. Further, these findings
      provide the basis for using simple cell culture systems to identify drugs that
      block the formation or release of A beta, the primary protein constituent of the
      senile plaques of Alzheimer's disease.

PMID- 1383827
TI  - Elongation factor-1 alpha gene determines susceptibility to transformation.
AB  - Elongation factor-1 alpha (EF-1 alpha), an essential component of the eukaryotic
      translational apparatus, is a GTP-binding protein that catalyses the binding of
      aminoacyl-transfer RNAs to the ribosome. Expression of the EF-1 alpha gene
      decreases towards the end of the lifespans of mouse and human fibroblasts, but
      forced expression of EF-1 alpha prolongs the lifespan of Drosophila melanogaster.
      Eukaryotic initiation factor-4E, another component of the translational
      machinery, is mitogenic or oncogenic when constitutively expressed in some
      mammalian cells. Thus, components of the protein synthesis apparatus seem to be
      involved in the control of cell proliferation. Using expression cloning, we have
      isolated a complementary DNA clone from a BALB/c 3T3 mouse fibroblast variant,
      A31-I-13 (ref. 10), which specifies a factor determining the susceptibility of
      BALB/c3T3 to chemically and physically induced transformation. Here we report
      that the factor is EF-1 alpha and that its constitutive expression causes BALB/c
      3T3 A31-I-1 (ref. 10), C3H10T1/2 (ref. 11) and Syrian hamster SHOK fibroblasts to
      become highly susceptible to transformation induced by 3-methylcholanthrene and
      ultraviolet light. EF-1 alpha messenger RNA is also constitutively expressed in a
      quiescent culture of the highly susceptible variant A31-I-13. We conclude that
      the removal of regulation of the expression of these components of the
      translational machinery may predispose cells to become more susceptible to
      malignant transformation.

PMID- 1383828
TI  - Cell transformation and activation of pp60c-src by overexpression of a protein
      tyrosine phosphatase.
AB  - The kinase activity of pp60c-src is specifically and transiently increased during
      mitosis and repressed during interphase. Loss of cell-cycle control of pp60c-src
      occurs on mutation of Tyr527 to Phe or when pp60c-src is associated with polyoma
      middle-T-antigen, and these conditions result in cell transformation or
      tumorigenesis. In both cases, pp60c-src has elevated kinase activity which is
      maintained throughout the cell cycle and accompanied by dephosphorylation of the
      carboxy-terminal negative regulatory Tyr527 site, or mimicry of Tyr527
      dephosphorylation in the case of the mutant. Here we report that overexpression
      of the receptor-like protein tyrosine phosphatase PTP alpha results in persistent
      activation of pp60c-src kinase, with concomitant cell transformation and
      tumorigenesis. In PTP alpha-overexpressing cells, the pp60c-src kinase activation
      is accompanied by dephosphorylation at Tyr527, and direct dephosphorylation of
      this site by purified PTP alpha occurs in vitro. Our results suggest that PTP
      alpha is involved in the regulation of cell proliferation, exerting at least some
      of its effects through pp60c-src kinase, and has oncogenic capability when
      overexpressed.

PMID- 1383829
TI  - Mutations in the channel domain of a neuronal nicotinic receptor convert ion
      selectivity from cationic to anionic.
AB  - Introduction by site-directed mutagenesis of three amino acids from the MII
      segment of glycine or gamma-aminobutyric acid (GABAA) receptors into the MII
      segment of alpha 7 nicotinic receptor was sufficient to convert a cation
      selective channel into an anion-selective channel gated by acetylcholine. A
      critical mutation was the insertion of an uncharged residue at the amino-terminal
      end of MII, stressing the importance of protein geometrical constraints on ion
      selectivity.

PMID- 1383830
TI  - Long-term proliferation of mouse primordial germ cells in culture.
AB  - Primordial germ cells (PGCs) are first identifiable as a population of about
      eight alkaline phosphatase-positive cells in the 7.0 days postcoitum mouse
      embryo. During the next 6 days of development they proliferate to give rise to
      the 25,000 cells that will establish the meiotic population. Steel factor is
      required for PGC survival both in vivo and in vitro and together with leukaemia
      inhibitory factor stimulates PGC proliferation in vitro. In feeder-dependent
      culture, PGCs will proliferate for up to 7 days, but their numbers eventually
      decline and their proliferative capacity is only a fraction of that seen in vivo.
      Here we report a further factor that stimulates PGC proliferation in vitro, basic
      fibroblast growth factor (bFGF). Furthermore, bFGF, in the presence of steel
      factor and leukaemia inhibitory factor, stimulates long-term proliferation of
      PGCs, leading to the derivation of large colonies of cells. These embryonic germ
      cells resemble embryonic stem cells, pluripotent cells derived from
      preimplantation embryos, or feeder-dependent embryonal carcinoma cells,
      pluripotent stem cells of PGC-derived tumours (teratomas and teratocarcinomas).
      To our knowledge, these results provide the first system for long-term culture of
      PGCs.

PMID- 1383831
TI  - Competitive PCR.

PMID- 1383832
TI  - Naloxone-reversible effect of spantide on the spinally mediated behavioural
      response induced by neurokinin-2 and -3 receptor agonists.
AB  - [D-Arg1, D-Trp7,9, Leu11]-substance P (spantide) was tested for antagonism
      against the licking, biting and scratching response induced by various neurokinin
      (NK) receptor agonists and bombesin (Bom) in mice. When co-administered with
      substance P (SP) intrathecally, spantide reduced the SP-induced behavioural
      responses in a dose-dependent manner. The duration of this antagonistic effect
      was approximately 30 min. Behavioural responses induced by physalaemin (Phy),
      [pGlu6, L-Pro9]-SP (6-11) (septide), [pGlu6, D-Pro7]-SP (6-11) (D-septide) and
      eledoisin (Ele) were also dose-dependently decreased by relatively small doses of
      spantide. Higher doses of spantide were needed to reduce the behavioural
      responses induced by [Sar9, Met (O2)11]-SP, neurokinin A (NK A) and neurokinin B
      (NK B). No significant effect of spantide was observed against the behavioural
      responses elicited by Bom. Pretreatment with naloxone, an opioid antagonist,
      resulted in a reversible effect on the behavioural reduction of NK-2 and NK-3
      receptor agonists produced by spantide. However, the effect of spantide on the NK
      1 receptor agonist-induced response was unchanged by naloxone. In homogenates of
      mouse spinal cord, competition studies confirmed that the binding of the opioid
      ligand [3H]naloxone was displaced by spantide with a low but measurable affinity.
      These results suggest that the behavioural response to NK-2 and NK-3 receptor
      agonists may be partially inhibited by spantide through the activation of opioid
      system in the mouse spinal cord.

PMID- 1383833
TI  - Role of cyclic AMP in the release of noradrenaline from isolated rat atria.
      Effect of pretreatment with clenbuterol.
AB  - The possible role of cyclic AMP (cAMP) on tritium overflow evoked by stimulation
      of the cardio-accelerant nerves was studied in rat atria preincubated with [3H]
      noradrenaline. Addition of the activator of adenylate cyclase forskolin (1
      mumol/l), or of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      (IBMX, 100 mumol/l), did not affect both basal and evoked overflow. However, in
      the presence of the alpha 2-adrenoceptor antagonist yohimbine (0.03 mumol/l) both
      forskolin and IBMX increased the stimulation-induced transmitter overflow by 49%
      and 141%, respectively (compared to yohimbine 0.03 mumol/l). Thus, in rat atria
      the cAMP-dependent facilitation of noradrenaline release is only present when the
      autoinhibition exerted by activation of prejunctional alpha 2-adrenoceptors is
      blocked. Propranolol (0.1 mumol/l) that did not produce any effect on
      noradrenaline release markedly reduced the facilitatory response induced by
      forskolin in the presence of yohimbine. When rats were pretreated with the beta 2
      adrenoceptor agonist clenbuterol (0.3 mg.kg-1, s.c., twice daily, 14 days), a
      treatment which desensitizes beta-adrenoceptor-mediated facilitation of
      noradrenaline release (Kazanietz and Enero 1989), the facilitatory effect of
      forskolin and IBMX in the presence of yohimbine was abolished. The results
      indicate that in rat atria the effect of forskolin and IBMX on noradrenaline
      release are only to be observed after blockade of presynaptic alpha 2
      adrenoceptor autoinhibition. beta-adrenoceptor blockade or clenbuterol
      pretreatment decreases the facilitatory response to forskolin and hence
      prejunctional beta-adrenoceptor-mediated enhancement of noradrenaline release is
      linked to the stimulation of adenylate cyclase.

PMID- 1383834
TI  - CP-96,345, a non-peptide antagonist of substance P: I. Effects on the actions
      mediated by substance P and related tachykinins on the guinea-pig ileum and
      rabbit jejunum.
AB  - The effects of a non-peptide antagonist of substance P, CP-96,345, were
      investigated, in vitro, on the guinea-pig ileum and the rabbit jejunum.
      Contractions of the guinea-pig ileum, induced by substance P and neurokinin A,
      were specifically inhibited by the racemate (+/-)CP-96,345 (pIC50 7.8 and 7.3,
      respectively). The inhibition by (+/-)CP-96,345 of contractions evoked by
      neurokinin B and by bradykinin (pIC50 6.1 and 4.9, respectively) was attributed
      to unspecific effects of the antagonist. The inhibition of substance P-induced
      contractions of the rabbit jejunum required a 10 times higher concentration of
      (+/-)CP-96,345 (pIC50 = 6.8) than was required with the guinea-pig ileum. The
      plateau phase of contraction of the guinea-pig ileum induced by high
      concentrations of substance P, neurokinin A or neurokinin B, which is known to be
      mediated through tachykinin receptors on intrinsic cholinergic neurones, was
      inhibited by 200 nM (+/-)CP-96,345 but not by the inactive enantiomer, CP-96,344.
      This indicates a specific inhibition of these neuronal tachykinin receptors by
      (+/-)CP-96,345. Contractions known to be mediated by the release of substance P,
      such as those evoked by capsaicin and by mesenteric nerve or field stimulation,
      were partially inhibited by (+/-)CP-96,345 at concentrations of 200 to 600 nM.
      Unspecific inhibitory effects of CP-96,345, in concentrations of 1 microM or
      higher, were observed on histamine-induced contractions, and on the cholinergic
      twitch response to electrical stimulation, of the guinea-pig ileum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1383835
TI  - CP-96,345, a non-peptide antagonist of substance P: II. Actions on substance P
      induced hypotension and bronchoconstriction, and on depressor reflexes in
      mammals.
AB  - In order to extend the in vivo pharmacological profile of CP-96,345 ((2S,3S)-cis
      2-(diphenylmethyl)-N-((2-methoxyphenyl)- methyl)-1-azabicyclo[2.2.2]octan-3-amine
      dihydrochloride), a non-peptide antagonist of substance P, the compound was
      tested against substance P-induced effects on blood pressure in rabbits and on
      respiration pressure in guinea-pigs. In addition, CP-96,345, and its inactive
      (2R,3R)-enantiomer, CP-96,344, were also tested in 2 models involving presumably
      substance P-mediated reflexes in the rat. The fall in blood pressure evoked by
      i.v. injections of substance P in the rabbit was inhibited by 0.3 mumol kg-1 CP
      96,345 i.v. for at least 30 min, and almost abolished, for at least 2 h, by 3
      mumol kg-1. In guinea-pigs, the bronchoconstriction induced by i.v. injections of
      substance P, but not that in response to histamine or bradykinin, was inhibited
      by CP-96,345 (0.6 and 6.0 mumol kg-1, i.v.) in a dose-dependent manner and this
      inhibition lasted for 40 min and 70 min, respectively. CP-96,345 (3-20 mumol kg
      1, i.v.) reduced depressor reflexes in response to stimulation of peripheral
      capsaicin-sensitive neurones in the rat. However, the inhibition was not dose
      dependent and was also seen with the inactive enantiomer, CP-96,344. This effect
      can hardly be attributed to receptor-specific effects of CP-96,345 and may be
      related to unspecific actions such as those involved in the cardiac depression
      exhibited by both enantiomers. The present results show that CP-96,345 is a
      potent antagonist of substance P in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383836
TI  - CP-96,345, a non-peptide antagonist of substance P. III. Cardiovascular effects
      in mammals unrelated to actions on substance P receptors.
AB  - The cardiovascular effects of CP-96,345, a non-peptide antagonist of substance P,
      were analyzed in vivo and in vitro. In the anaesthetized rat, the i.v. injection
      of 3 mumol kg-1 of CP-96,345 induced a fall in mean arterial blood pressure and a
      reduction in heart rate. Similar effects were obtained with the enantiomer CP
      96,344 (2R,3R)-cis-isomer of CP-96,345) which does not interact with substance P
      receptors. Both enantiomers, at a concentration of 10 microM, decreased the
      beating frequency of the isolated atria and of the isolated perfused heart of the
      guinea-pig to a similar extent, and caused transient coronary dilatation. CP
      96,345 (10 microM) decreased the spontaneous sinus rate, prolonged the
      atrioventricular-nodal conduction interval and the His-bundle conduction interval
      of the perfused guinea-pig heart. The intraventricular spread of conduction was
      markedly inhibited. During programmed stimulation 10 min after the beginning of
      the drug application, the effective refractory periods evaluated by stimulation
      with premature beats, as well as rate dependent effective refractory periods, of
      the atrioventricular node, of the atrial and of the ventricular myocardium, were
      prolonged. Sinus node recovery time was also prolonged. It was concluded that
      these cardiac effects of CP-96,345 were not caused by an action of the compound
      on substance P receptors.

PMID- 1383838
TI  - [Cough as a side effect of angiotensin-converting enzyme inhibitors].

PMID- 1383837
TI  - Effects of the novel calcium channel blocker, anipamil, on the isolated rabbit
      heart. Comparison with verapamil and gallopamil.
AB  - The calcium channel blocking activity of the novel phenylalkylamine derivative,
      anipamil, was tested on the isolated rabbit heart, in comparison with verapamil
      and gallopamil. Anipamil and the other calcium channel blockers lower left
      ventricular pressure in the same concentration range (10(-8)-10(-4) mol/l). The
      negative inotropic effect of anipamil is only partially reversed (nearly 65%) by
      rising calcium concentration in the perfusion fluid, whilst a complete recovery
      is observed for verapamil and gallopamil. The negative inotropic effect of
      anipamil is of rapid onset but long lasting, being still present 12 h after
      washout. On the contrary, that of gallopamil or verapamil completely disappears
      within 3 h of washout. Verapamil and gallopamil (10(-8)-10(-4) mol/l) depress
      spontaneous heart rate up to asystolia and abolish the vasopressin- and Bay K
      8644-induced coronary spasm. Anipamil, on the contrary, does not modify coronary
      spasm elicited by both stimulants and spontaneous heart rate up to 10(-4) mol/l.
      These observations suggest that anipamil, in the isolated rabbit heart, possesses
      a peculiar pharmacological profile, since its calcium channel blocking activity
      is confined to the myocardial muscle.

PMID- 1383839
TI  - [Gram staining and bacterial culture of stomach contents of the full-term neonate
      in prolonged status of ruptured membranes is not useful].
AB  - In an effort to evaluate the management of full-term neonates born after
      prolonged rupture of the membranes, we studied 159 full-term newborn infants born
      24 hours or more after rupture of the membranes retrospectively. Gram stain and
      bacterial culture of a gastric aspirate of the neonates were significantly
      related; however, the predictive value of the Gram stain was low, both for a
      positive test (46%) and for a negative test (70%). A significant relation was not
      found between the Gram stain (presence of bacteria or greater than or equal to 4
      leucocytes per high power field) or the bacterial culture on the one hand and the
      occurrence of clinical symptoms of infection on the other. In all cases the
      decision to treat the newborn with antibiotics was made on the basis of the
      clinical symptoms alone. In our opinion the routine study of Gram stain and
      bacterial culture of a gastric aspirate of full-term neonates born after
      prolonged rupture of the membranes is not useful; observation alone is
      sufficient.

PMID- 1383840
TI  - Hepatitis C.
AB  - Until recently the diagnosis of non-A, non-B hepatitis was made by excluding
      other detectable viral infections of the liver. Progress in molecular biology
      made it possible to develop assays which can trace antibodies against the
      hepatitis C virus. This virus plays a major role in the pathogenesis of
      transfusion-related and sporadic non-A, non-B hepatitis and possibly of other
      liver diseases. Although the genome of a few isolates of the hepatitis C virus
      has already been decoded, the viral particles have not yet been visualized.

PMID- 1383841
TI  - Degradation of myelin basic protein by a membrane-associated metalloprotease:
      neural distribution of the enzyme.
AB  - A metalloprotease activity associated with myelin membrane preparations degrades
      myelin basic protein (MBP), generating a characteristic fragment designated
      peptide C (MBP 74-170). Using an immunoblotting assay, peptide C-generating
      activity was detected in mammalian, avian, reptilian, and amphibian brains. The
      activity was present in rat brain as early as postnatal day 1 and also in adult
      rat peripheral nerve. Immunohistochemistry with a monoclonal antibody to the
      purified enzyme revealed that the metalloprotease was present in oligodendrocytes
      of optic nerve, of both white and grey matter of spinal cord, and also in the
      cytoplasm of both myelinating and nonmyelinating Schwann cells of peripheral
      nerve.

PMID- 1383843
TI  - Rapid morphological changes in bovine brain microvascular endothelial cells on
      extracellular matrices.
AB  - The morphological changes in endothelial cells derived from bovine brain
      microvasculature, carotid artery, and aorta during growth on extracellular
      matrices were compared. All cells formed tubular structures on a basement
      membrane. Ultrastructural studies showed that the tubular structures had lumens
      surrounded by many endothelial cells. On type I collagen gel, brain microvascular
      endothelial cells still formed tubular structures, but the other two cell types
      formed confluent monolayers. However, when a second layer of collagen gel was
      laid over these cells, tubular structures developed within 2-3 days. Brain
      microvascular endothelial cells form tubular structures more readily than
      endothelial cells derived from large vessels on both basement membrane and type I
      collagen gel.

PMID- 1383842
TI  - Molecular mimicry and the autoimmune response to the peripheral nerve myelin P0
      glycoprotein.
AB  - In the Lewis rat immunisation with the myelin P0 glycoprotein can induce an
      inflammatory demyelinating disease of the peripheral nervous system, experimental
      allergic neuritis (EAN), which has many clinical and histopathological parallels
      with the human disease the Guillain-Barre syndrome. In view of the reported
      association of GBS with a number of infectious agents we have investigated
      whether "molecular mimicry" may occur between microbial antigens and the P0
      protein that could possibly trigger a similar pathogenic autoimmune response in
      man. A computer search of the available protein sequence data bases identified
      several absolute sequence homologies between P0 and viral proteins that involve
      five or more consecutive amino acid residues. Four of these sequence homologies
      involved viral pathogens previously associated with the Guillain-Barre syndrome,
      namely Epstein-Barr virus (EBV), cytomegalovirus (CMV), Varicella zoster virus
      (VZV) and human immunodeficiency virus I (HIV I). Although, sequence homologies
      were also found between viral peptides and the neuritogenic determinants of P0,
      residues 56-71 and 180-199, these homologies proved incapable of eliciting EAN in
      the Lewis rat. These observations are discussed with reference to the role that
      molecular mimicry between T cell epitopes on pathogen derived antigens and the P0
      protein may play in the pathogenesis of the Guillain-Barre syndrome.

PMID- 1383844
TI  - Morphometrical analysis of GFAP-positive cells in human astrocytomas.
AB  - The morphometrical characteristics of human astrocytoma were examined using the
      shape, size, and intercellular distances of glial fibrillary acidic protein
      positive cells in samples from 21 patients with various astrocytomas and normal
      samples resected during operations on seven patients with other brain tumors. The
      results showed that astrocytoma cells were rounder than normal astrocytes with
      fewer processes. Low-grade astrocytomas were smaller than astrocytes or rapid
      regrowth astrocytomas. Morphological analysis of astrocytoma may be valuable for
      evaluating the potential migration to adjacent tissue.

PMID- 1383845
TI  - Immunohistochemical study of a newly defined oncofetal antigen (HGR-Ag) in tumors
      of the central nervous system.
AB  - The oncofetal antigen (HGR-Ag) in brain tumors was newly defined using the
      monoclonal antibody derived from tissue extracts of an anaplastic astrocytoma.
      The HGR-Ag was purified through sequential chromatography using diethylaminoethyl
      Sephadex A-50 and Con-A Sepharose affinity columns. The latter method indicated
      that HGR-Ag is not a glycoprotein, and Western blot analysis indicated a
      molecular weight of 80-90 kd. Purified antigen was used to produce antibody. This
      new antibody, designated H1H2, was shown to be an immunoglobulin G1 by
      immunodiffusion assay. Histological/immunohistochemical studies using the H1H2
      antibody on paraffin and frozen tissue sections showed HGR-Ag to be intracellular
      rather than membrane-associated. The immunoreactivity of H1H2 was highest in
      malignant astrocytomas, glioblastomas, and normal fetal brain tissue. Neurinomas
      and certain carcinomas of other organs showed lesser, variable reactivity to
      H1H2. The strength of the antigen-antibody binding was correlated with the degree
      of malignancy in human gliomas. H1H2 bound to fetal brain tissue and
      undifferentiated neural tumors, but not to normal adult brain tissue, so HGR-Ag
      is probably a fetal oncoantigen.

PMID- 1383847
TI  - Stereotactic radiosurgery using a linear accelerator.
AB  - A basic and clinical study of radiosurgery using the linear accelerator (Linac)
      system for unremovable deep-seated brain tumors is reported. A Komai stereotactic
      ring was used to locate the target coordinates. The patient was laid on the Linac
      treatment table and held in the head fixation system. Irradiation was given in
      five positions. The dose profile by film dosimetry and Rando phantom was
      satisfactory. Seventeen tumors in 14 patients were treated. Clinical or
      histological diagnoses were nine metastases, one benign and two malignant
      gliomas, one meningioma, and one craniopharyngioma. Tumor sizes were between 8
      and 30 mm. Doses were between 12 and 30 Gy. Computed tomographic evaluation after
      3 months of 12 tumors in 11 survivors showed one complete remission, three
      partial remission, six no change, and two partial deterioration. For progressive
      tumors, Linac radiosurgery results are excellent.

PMID- 1383846
TI  - Postauricular response in motor paresis with intracranial lesions.
AB  - The clinical usefulness of the postauricular response (PAR) in the evaluation of
      motor paresis was studied in 105 patients with intracranial lesions and 25 normal
      volunteers. Click stimuli at 90 dB hearing level were delivered in each ear, and
      PARs recorded from bilateral posterior auricular muscles with reference to the
      vertex (Cz). No volunteer demonstrated PAR in the relaxed posture, but in tensed
      postures increasing muscle tone PARs were elicited with a latency of 11.5 +/- 0.7
      msec and an amplitude of 6.2 +/- 2.8 muV. Sixty-two patients (59%) had high
      amplitude PARs in the relaxed posture. PARs were enhanced more frequently in
      paretic patients than in non-paretic patients (p less than 0.01). In subcortical
      lesions, the PAR latency had a significant correlation with the degree of motor
      paresis (p less than 0.005). In patients, the enhanced PAR amplitude suggested
      the presence of motor paresis associated with deep-seated mass lesions. The
      enhanced response is thought to be associated with dysfunction of the pyramidal
      and extrapyramidal tracts.

PMID- 1383848
TI  - Angiographically occult arteriovenous malformation in the septal region--case
      report.
AB  - An occult arteriovenous malformation (AVM) in the septal region occurred in a 14
      year-old boy, manifesting as headache and vomiting. Computed tomography showed a
      high-density mass in the septal region, faintly enhanced postcontrast. Mild
      hydrocephalus was also seen. Angiography revealed no abnormalities other than
      hydrocephalic signs. The lesion was totally removed by the transventricular
      approach after corticotomy of the left frontal lobe. The histological diagnosis
      was AVM. He was discharged without neurological or endocrinological deficits.

PMID- 1383849
TI  - Foramen magnum meningioma and arachnoid cyst coinciding in the lateral
      cerebellomedullary cistern--case report.
AB  - An extremely rare foramen magnum meningioma associated with an arachnoid cyst in
      the lateral cerebellomedullary cistern occurred in a 65-year-old female
      presenting with dizziness. Neuroimaging revealed a meningioma at the left lateral
      edge of the foramen magnum and an arachnoid cyst mainly located in the right
      lateral cerebellomedullary cistern, compressing the medulla oblongata
      bilaterally. After fenestration of the cyst wall and tumor removal, the clinical
      symptoms ameliorated. We recommend that where a foramen magnum tumor coexists
      with an arachnoid cyst of the posterior fossa, the tumor should be removed after
      shrinking the cyst to obviate the need for brainstem retraction.

PMID- 1383850
TI  - Enlargement of cerebellar arteriovenous malformation associated with fenestration
      of the vertebral artery--case report.
AB  - We report a 30-year-old male case of an enlarged cerebellar arteriovenous
      malformation (AVM) associated with fenestration of the vertebral artery.
      Hemodynamic stress resulting from fenestration of the feeding system of AVM was
      probably an important factor in the enlargement of the small cerebellar AVM.

PMID- 1383851
TI  - Transpetrosal extreme lateral suboccipital approach for extensive posterior fossa
      epidermoid cyst--case report.
AB  - A new transpetrosal extreme lateral suboccipital approach was adopted to totally
      remove an extensive posterior fossa epidermoid cyst in a 36-year-old male. The
      pathological behavior of intracranial epidermoid cysts may impose surgical
      problems during removal of the tumor. However, planning based on neuroimaging
      allows optimum access to tumors and microsurgery achieves safer and more complete
      removal.

PMID- 1383852
TI  - Lectin cytochemistry combined with silver colloid staining of argyrophilic
      nucleolar organizer regions in human gliomas.
AB  - Investigation of lectin cytochemical staining of inflammatory cells in human
      gliomas showed that Allomyrina dichotoma (Allo-A) cytochemistry can reliably
      distinguish inflammatory from neoplastic cells. Allo-A cytochemistry combined
      with silver colloid staining of argyrophilic nucleolar organizer regions (Ag
      NORs) was performed in human gliomas. Inflammatory cells possessed usually one
      but sometimes two Ag-NORs and macrophages often possessed several Ag-NORs. The
      mean Ag-NOR number per nucleus of inflammatory cells ranged from 1.81 to 2.34,
      and that of neoplastic cells ranged from 2.57 to 3.53 and from 2.84 to 4.46 in
      low- and high-grade gliomas, respectively. The mean Ag-NOR number per nucleus of
      inflammatory cells was significantly smaller than that of neoplastic cells (p
      less than 0.001). Combined Allo-A cytochemical and silver colloid Ag-NOR staining
      can provide a reliable Ag-NOR number in human gliomas by distinguishing
      inflammatory cells.

PMID- 1383853
TI  - Indications for surgery and prognosis in patients with cerebral cavernous
      angiomas.
AB  - Seventy-three cerebral cavernous angiomas were removed microsurgically from a
      series of 71 patients between August, 1983 and December, 1989. This retrospective
      investigation assessed the current indications for surgery and determined the
      prognosis for patients with cerebral cavernous angioma. There were 38 males and
      33 females with a mean age of 37 years. Analysis included clinical presentation
      and history, neuroradiological findings, indications for surgery, and
      postoperative course. After an average follow-up period of 15 months, 35 patients
      were symptom-free, 16 had improved preoperative complaints, six were unchanged,
      and eight had deteriorated. Microsurgical extirpation of the malformation is
      indicated in all symptomatic patients where neuroimaging demonstrates the
      presence of a readily accessible cerebral cavernoma. Surgery is recommended in
      cases with deep-seated lesions causing massive hemorrhage, repetitive minor
      bleeding, or significant long-standing and progressive neurological disabilities.
      Clinically silent cavernomas located in eloquent regions of the brain
      contraindicate surgery, but should be closely monitored. Patients presenting with
      convulsions or neurological deficits caused by easily accessible cavernomas of
      the hemispheres have the best prognosis and a negligible risk for surgical
      complications. Those with deep-seated lesions of eloquent regions of the brain
      that have bled or caused sustained neurological disorders face the highest risk
      for morbidity owing to the surgical intervention, requiring careful preoperative
      evaluation.

PMID- 1383854
TI  - Risk factors for brain abscess in patients with congenital cyanotic heart
      disease.
AB  - Brain abscess is a serious complication of congenital cyanotic heart disease. We
      retrospectively evaluated the risk factors for brain abscess in 21 such patients
      treated between 1975 and 1990 in comparison with a control group. The mean
      arterial oxygen saturation, arterial partial pressure of O2, arterial blood
      oxygen content, and base excess in patients with brain abscess were significantly
      lower than in the control patients. The mean arterial partial pressure of CO2,
      pH, hematocrit, hemoglobin, and red blood cell content in patients with brain
      abscess were not significantly different. Patients with congenital cyanotic heart
      disease may develop minute encephalomalacia due to severe hypoxemia and increased
      blood viscosity resulting from compensatory polycythemia. The increased blood
      viscosity and reduced blood flow in the microcirculation may induce cerebral
      thrombosis or exaggerate minute encephalomalacia during dehydration or cardiac
      dysfunction, and shunted blood containing infectious organisms at such sites may
      be followed by focal cerebritis.

PMID- 1383855
TI  - Evaluation of therapeutically induced hypertension in patients with delayed
      cerebral vasospasm by xenon-enhanced computed tomography.
AB  - Serial cerebral blood flow (CBF) measurements were made with stable xenon
      enhanced computed tomography in 20 patients with angiographically confirmed
      ruptured intracranial aneurysms, before and during induced hypertension with
      continuous infusion of dopamine. All patients showed angiographic vasospasm
      during their course. Twelve patients without symptomatic vasospasm (Group 1) had
      the lowest hemispheric CBF on the craniotomy side of 31.6 +/- 6.8 ml/100 gm/min
      on days 4-9 (control value, 40.1 +/- 2.0 ml/100 gm/min), while the other eight
      patients with symptomatic vasospasm (Group 2) had the lowest hemispheric CBF on
      the craniotomy side of 25.0 +/- 7.6 ml/100 gm/min on days 10-14. The critical
      hemispheric CBF inducing neurological deficits was about 20 ml/100 gm/min in
      Group 2. Dysautoregulation was usually present in Groups 1 and 2, but
      therapeutically induced hypertension could reverse the delayed neurological
      deficits, if begun early at the stage of delayed vasospasm.

PMID- 1383856
TI  - Treatment of unclippable giant posterior cerebral artery aneurysms with
      detachable balloons--report of three cases.
AB  - Three patients presented with rare giant posterior cerebral artery aneurysms,
      clinically manifesting as cerebral ischemia, mass effect, and subarachnoid
      hemorrhage. All aneurysms were partially thrombosed, originated at the P2
      segment, and possessed broad necks. Surgical neck clipping was difficult but
      proximal occlusion of the parent artery was feasible. Aneurysm occlusion sparing
      the parent artery was attempted in all cases, but failed because the detachable
      balloon did not successfully block the aneurysmal neck. All patients tolerated
      test occlusion at the P2 segment, so the parent artery was occluded proximally
      with detachable balloons, leaving the important perforating arteries unaffected.
      Two transient ischemic attacks were associated with the procedure. Where surgical
      treatment is unusually difficult, and proximal ligation or trapping just
      feasible, embolization with detachable balloons is an acceptable substitute.

PMID- 1383857
TI  - Chronic subdural hematoma following bypass surgery--report of three cases.
AB  - Bypass surgery is a safe procedure with low mortality and morbidity, and few
      reported surgical complications. Three patients developed postoperative chronic
      subdural hematoma (CSDH): two with stroke after superficial temporal artery
      middle cerebral artery (STA-MCA) anastomosis and one with moyamoya disease after
      STA-MCA anastomosis combined with encephalomyosynangiosis. The factors inducing
      CSDH after revascularization in the seven reported and present cases included
      postoperative subdural effusion associated with brain atrophy, and postoperative
      anticoagulant therapy such as aspirin. CSDH may occur in patients with pre
      existing brain atrophy and postoperative subdural effusion. Anticoagulant therapy
      should be avoided at the early postoperative stage after bypass surgery.

PMID- 1383858
TI  - Bilateral posterior fossa epidural hematoma--report of two cases.
AB  - Two cases of posttraumatic bilateral posterior fossa epidural hematoma are
      presented. Such hematomas are extremely rare, but can be surgically cured.
      Computed tomography helps to establish the diagnosis and determine the
      neurosurgical treatment.

PMID- 1383859
TI  - Giant aneurysm of the azygos anterior cerebral artery associated with acute
      subdural hematoma--case report.
AB  - A ruptured giant aneurysm of the azygos anterior cerebral artery (ACA) associated
      with an acute subdural hematoma (SDH) occurred in a 67-year-old male with two
      episodes of sudden severe headache and transient loss of consciousness.
      Neurologically, he had mild weakness of the left lower extremity. Computed
      tomography showed an elliptical heterogeneous hyperdense mass in the
      interhemispheric fissure in front of the corpus callosum and an acute SDH on the
      right. Angiography disclosed a giant aneurysm (2.8 x 2.0 cm) at the distal end of
      the azygos ACA. Removal of the SDH and aneurysmal neck clipping achieved a good
      outcome. Successive small bleedings may allow the aneurysmal dome to develop
      adhesions to the arachnoid membrane, and the final rupture will occur into the
      subdural space, resulting in a SDH.

PMID- 1383860
TI  - Dynamic magnetic resonance appearance of the vertebral dissecting aneurysm--case
      report.
AB  - A dissecting aneurysm of the vertebral artery occurred in a 38-year-old male
      presenting with ischemic attacks. Vertebral angiography revealed irregular
      narrowing and dilatation of the right vertebral artery, and retention of the
      contrast medium. Routine T1-weighted magnetic resonance (MR) imaging demonstrated
      signal voids compatible with a patent but narrowed vertebral lumen surrounded by
      three intensity components at the abnormality location identified on the
      vertebral angiograms. Dynamic MR imaging demonstrated strong enhancement of these
      components on the early images. These findings were consistent with the false
      lumen of the dissecting aneurysm. The different signal intensities were thought
      to reflect the blood flow rate.

PMID- 1383861
TI  - Suprasellar malignant teratoma with 11-year survival--case report.
AB  - Long-term survival of malignant teratoma is rare. A 16-year-old female with a
      suprasellar malignant teratoma survived for 11 years before succumbing to
      embryonal carcinoma. A suprasellar immature teratoma with increased serum alpha
      fetoprotein level was verified histologically. Radiation therapy and combined
      chemotherapy were given after partial removal. Eleven years later, the primary
      lesion recurred as embryonal carcinoma.

PMID- 1383862
TI  - A study of evoked potentials in the 18q-syndrome which includes the absence of
      the gene locus for myelin basic protein.
AB  - We report evoked potential findings in a patient with 18q-syndrome (18q22.3---
      qter). The deletion included the locus for myelin basic protein (MBP). Clinical
      manifestations were mild intellectual deficit, involuntary movements and ataxia.
      MRI of the brain showed diffusely abnormal white matter. Visual evoked responses
      were normal. Central conduction was prolonged on median somatosensory evoked
      potentials and no central response was seen with posterior tibial somatosensory
      potentials. Putative congenital deficiency of MBP does not necessarily cause
      abnormal visual evoked responses.

PMID- 1383863
TI  - Stimulation of 5-HT1 receptors in the spinal cord changes substance P-induced
      behaviour.
AB  - This study examined whether intrathecal (i.th.) injection of different 5
      hydroxytryptamine (5-HT) receptor agonists modulated the behavioural response to
      substance P. Given intrathecally, substance P produces a behavioural syndrome
      consisting of biting of the lower parts of the abdomen and reciprocal hindlimb
      scratching, which may be indicative of nociceptive stimulation. The number of
      substance P-induced bites was reduced when counted 5 min after intrathecal
      injection of 5-HT, p-chloroamphetamine (PCA) which causes release of 5-HT from
      neuronal terminals, the non-selective 5-HT receptor agonist quipazine, the
      selective 5-HT1 receptor agonists (+)-8-hydroxy-2-(di-n-propylamino)tetralin [(+)
      8-OH-DPAT], 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969) and
      1(m-chlorophenyl)piperazine (mCPP), but was unchanged by treatment with the 5
      HT2/5-HT1C receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      (DOI). The number of scratches was significantly increased 5 min after injection
      of 5-HT and RU 24969. The results showed that intrathecal injection of 5-HT
      agonists, with a high affinity for the 5-HT1 receptor subtypes, reduced the total
      number of responses induced by intrathecal injection of substance P, whereas a 5
      HT2/5-HT1C receptor agonist did not affect the behavioural response to the
      intrathecal injection of substance P.

PMID- 1383864
TI  - Spinal and intestinal levels of substance P, calcitonin gene-related peptide and
      vasoactive intestinal polypeptide following perendoscopic injection of formalin
      in rat colonic wall.
AB  - Acute inflammation of the colonic wall was induced by perendoscopic injection of
      formalin in rats. As compared to control animals (no endoscopy, no injection),
      the procedure was followed by a marked reduction of immunoreactive substance P,
      calcitonin gene-related peptide and vasoactive intestinal peptide concentrations
      in rectosigmoid wall. Tissue substance P concentration in the spinal cord, at the
      level of afferent projection, increased at the same time. The three peptides
      tested are thus likely to be involved in the pathophysiology of acute intestinal
      inflammation. In addition, substance P may play a role in the transmission of
      nociceptive signals from the inflamed colonic segment.

PMID- 1383866
TI  - Primary choroid plexus papilloma located in the suprasellar region: case report.
AB  - A 34-year-old woman with primary choroid plexus papilloma occurring in the
      suprasellar region is reported. No connection with the ventricular system was
      found during intraoperative observations. The findings of pathological
      examinations such as hematoxylin and eosin staining, transthyretin (prealbumin)
      immunoreactivity, and electron microscopy were consistent with choroid plexus
      papilloma. Radiologically, it was extremely difficult to differentiate from
      tuberculum sellae meningioma. To our knowledge, this is the first case of primary
      choroid plexus papilloma in this location reported in the literature.

PMID- 1383865
TI  - The effect of p-chloroamphetamine and p-chlorophenylalanine on the level of
      thyrotropin-releasing hormone and its receptors in some brain structures and
      lumbar spinal cord of the rat.
AB  - The concentration of thyrotropin-releasing hormone (TRH) and the density and
      affinity of TRH receptors were examined in the ventral and dorsal lumbar spinal
      cord, nucleus accumbens and striatum of rats with the 5-hydroxytryptamine (5-HT)
      nerve terminal destroyed with p-chloroamphetamine (PCA), or in animals treated
      with the inhibitor of 5-HT synthesis p-chlorophenylalanine (PCPA). PCA (2 x 10
      mg/kg i.p., 9 and 8 d before killing) and PCPA (3 x 300 mg/kg i.p., 72, 48 and 24
      h before killing)--either of them dramatically diminishing the 5-HT and 5-HIAA
      concentrations in all the examined structures--reduced the TRH level and
      increased the density of TRH receptors in the ventral lumbar spinal cord. PCPA
      also reduced the TRH content in the nucleus accumbens. The PCA-induced reduction
      in the TRH level and increase in the density of TRH receptors in the ventral
      lumbar spinal cord were significantly attenuated by citalopram (2 x 20 mg/kg
      i.p., 30 min before PCA), a selective inhibitor of 5-HT uptake. Our results
      constitute a further proof that coexistence of TRH and 5-HT takes place in the
      ventral lumbar spinal cord and then indicate that other form(s) of relationship
      between 5-HT and TRH may exist in some parts of the central nervous system. They
      also suggest that an up-regulation of TRH receptors occurs in the spinal cord as
      a result of TRH depletion.

PMID- 1383867
TI  - Dose changes in long- and medium-term intrathecal morphine therapy of cancer
      pain.
AB  - Intrathecal morphine analgesia for the treatment of cancer pain was administered
      using implanted ports and drug delivery systems (DDS) in 79 patients. Effective
      control of the pain was achieved in nearly all patients; in only two patients was
      the use of the DDS discarded because of relative ineffectiveness. Fifty-three
      manual drug release systems (41 lumbar, 12 ventricular) and 26 lumbar ports were
      used. Forty patients survived more than 2 months; the maximum survival time was
      560 days (mean survival time, 80 days with a port system, 100 days with a manual
      DDS). Patients still alive at the time of this study, i.e., with unknown survival
      time, were excluded. The initial mean daily dose was 8.5 mg in lumbar ports, 2.75
      mg in lumbar DDS, and 0.2 mg with intraventricular application. Dose change
      patterns disclosed no alteration of the initial dose in 18 of 26 port patients,
      an initial increase in 4, a preterminal increase in 3, and a single intermittent
      increase in 1 patient. Of 40 lumbar DDS patients, 13 showed a constant dose, 9 an
      initial, 3 a preterminal, and 5 an intermittent increase. Three patients with
      less than 2 months' survival time had a rather continuous increase. All long-time
      survivors (i.e., with more than 2 months' survival time) reached a plateau and
      remained there until a preterminal if any increase occurred. These findings
      suggest the morphine dosage to be indicative of the progress of the disease
      rather than of a drug tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383868
TI  - Selective participation of brain-specific nonhistone Np-3.5 proteins of chromatin
      in the processes of the reproduction of a defensive habit in response to food in
      edible snails.
AB  - The role of brain-specific nonhistone Np-3.5 proteins of chromatin in the
      processes of the reproduction of a developed defense habit in response to food
      was studied in preliminarily trained edible snails. It was found that gamma
      globulins to Np-3.5 over the course of tens of minutes suppress behavioral and
      neuronal reactions elicited by a specific conditional stimulus, carrot juice,
      while not altering the reaction to a different conditional stimulus, apple juice.
      The gamma globulins to other nonhistone proteins of chromatin did not exert an
      influence on the reproduction of habits of food rejection. It is hypothesized
      that brain-specific nonhistone Np-3.5 proteins of chromatin are selectively
      involved in the molecular processes supporting the neurophysiological mechanisms
      of the extraction of information from long-term memory.

PMID- 1383869
TI  - Morphological differences between projection neurons of the core and shell in the
      nucleus accumbens of the rat.
AB  - The somatodendritic morphology of projection neurons in the shell and core of the
      rat nucleus accumbens was studied. These cells were retrogradely labelled with
      Fast Blue from the ventral mesencephalon (substantia nigra/ventral tegmental
      area) and subsequently injected intracellularly with Lucifer Yellow and processed
      immunocytochemically. Digitized reconstructions revealed that the cell bodies of
      neurons located throughout the nucleus are small-to-medium in size. Neurons in
      the shell have significantly fewer dendritic arbours with fewer branch segments,
      fewer terminal segments, and lower spine densities than those in the core. Values
      for the same parameters are significantly greater for cells in lateral than in
      medial parts of the shell but the same for neurons located within and without
      enkephalin enriched parts of the core, with an exception of spine density being
      significantly greater in the enkephalin-rich compartment. Calculations based on
      these data reveal that neurons in the core have as much as 50% more surface area
      than those in the shell, which suggests that core neurons have a greater
      potential for collecting synaptic information than have shell cells. Furthermore,
      the differential distribution and action of various neurochemicals such as
      dopamine in the shell and core, supports the idea that different morphologies
      reflect the presence of distinct neuronal circuits in these two territories.

PMID- 1383871
TI  - Monoclonal antibody BM89 recognizes a novel cell surface glycoprotein of the
      L2/HNK-1 family in the developing mammalian nervous system.
AB  - A monoclonal antibody, BM89, obtained with Triton X-114-treated pig synaptic
      membranes as an immunogen, recognizes a neuronal antigen in the newborn porcine
      nervous system. By immunohistochemistry, BM89 staining was observed within the
      neuropil of all areas of the forebrain and spinal cord tested. In addition, BM89
      labeled the cell bodies and proximal dendrites of spinal cord neurons. In the
      peripheral nervous system, BM89 immunoreactivity was present in a subpopulation
      of dorsal root ganglion neurons and was predominantly associated with non
      myelinated axons in peripheral nerves. Initial biochemical characterization of
      the antigen in pig brain showed that it is an integral membrane glycoprotein with
      a molecular weight of 41,000. Moreover, it cross-reacts with the L2/HNK-1
      carbohydrate epitope expressed by members of a large family of glycoproteins.
      Homologous antigens with molecular weights of 41,000-43,000 were identified in
      the rat, rabbit and fetal human brain. Immunoblotting and immunohistochemistry
      revealed that the epitope recognized by BM89 is developmentally regulated in the
      rat nervous system. In cryostat sections from rat cerebellum, spinal cord and
      dorsal root ganglia, an age-dependent decline of BM89 immunoreactivity was
      observed during postnatal development. In the cerebellum, the BM89 epitope was
      very abundant in cells of the external and the internal granular layers between
      postnatal days 5 and 15. During this period some staining was also identified in
      the developing molecular layer and the prospective white matter. Subsequently,
      and in the adult, overall staining was greatly reduced and remaining
      immunoreactivity was associated only with the internal granular layer. In the
      spinal cord and dorsal root ganglia, staining was very prominent at postnatal day
      5; it decreased considerably thereafter and was barely detectable in the adult.
      Immunostaining of rat brain and dorsal root ganglion cultures revealed that the
      BM89 antigen is a cell surface molecule expressed by a subpopulation of central
      and peripheral nervous system neurons. The biochemical properties in conjunction
      with the topographical location and the developmental profile of the antigen
      recognized by BM89 suggest that it may represent a developmentally important
      recognition molecule.

PMID- 1383870
TI  - Alteration in the levels of thyrotropin releasing hormone, substance P and
      enkephalins in the spinal cord, brainstem, hypothalamus and midbrain of the
      Wobbler mouse at different stages of the motoneuron disease.
AB  - The present study was undertaken to quantify selected neuropeptides (thyrotropin
      releasing hormone, substance P, methionine and leucine enkephalin) in the
      cervical spinal cord and other regions of the central nervous system of Wobbler
      mice by radioimmunoassays during several stages of the motoneuron disease
      compared with age- and sex-matched normal phenotype littermates. In Wobbler
      spinal cord, thyrotropin releasing hormone is higher early in the disease,
      whereas in the brainstem it is higher at a later stage. Substance P in spinal
      cord is also higher late in the disease. Leucine enkephalin levels are greater at
      all stages in diseased spinal cord and brainstem, but methionine enkephalin
      increases only late in the disease. Highly significant increases of the peptides
      (except thyrotropin releasing hormone) appear in hypothalamus and midbrain only
      late in the motoneuron disease. Regression analyses show that thyrotropin
      releasing hormone in spinal cord and brainstem decreases normally with age in the
      control mice and at a faster rate related to the extent of motor impairment in
      Wobbler mice. Thyrotropin releasing hormone and methionine enkephalin in the
      Wobbler brainstem correlate (P less than 0.05) with the progress of the
      motoneuron disease. Methionine enkephalin increases faster in Wobbler brainstem
      and decreases faster in control spinal cord with age. The increase of leucine
      enkephalin in the Wobbler spinal cord correlates significantly with age and with
      the progress of the disease, but leucine enkephalin declines slightly with age in
      the controls. The changes of substance P in spinal cord and brainstem do not
      correlate significantly with the progress of the disease. In the hypothalamus,
      increasing values for substance P in control specimens and enkephalins in Wobbler
      specimens are significantly correlated with age. However, in the midbrain, higher
      methionine and leucine enkephalin levels are significantly associated with age
      only in the control mice. Alterations of neuropeptides in the Wobbler mouse
      spinal cord and brainstem may result from the degeneration of bulbospinal raphe
      neurons projecting to the ventral spinal cord, or from primary afferent or
      interneuronal nerve terminals. The data imply that the neuronal degeneration
      process in the Wobbler motoneuron disease is not limited to motoneurons. In the
      spinal cord, the data support our previous hypothesis that neuronal sprouting
      presynaptic to the motoneurons may account for increased neuropeptide
      concentrations. Alternatively, synthesis and/or degradation of these peptides may
      be altered. In addition, it is proposed that enkephalinergic neurons may develop
      abnormally in Wobbler mice. The early increase of leucine enkephalin in the
      Wobbler spinal cord possibly indicates its importance in the etiology of the
      motoneuron disease.

PMID- 1383873
TI  - [Arrhythmogenic Takayasu disease].
AB  - The Authors report a case of Takayasu disease in a woman who died at the age of
      forty-six, in whom the histological examination of the cardio-vascular system
      revealed giant cells granulomatous arteritis localized in the aortic arch and
      collateral arteries; endocarditis and granulomatous coronaritis. The bases of
      arrhythmogenic alterations, in this study, take into account the thrombosis of
      the conduction system arteriolar vessels and the phlogosis extending to the
      cardiac plexus.

PMID- 1383872
TI  - Amyloidoma of the CNS. II. Immunohistochemical and biochemical study.
AB  - We present the immunohistochemical and biochemical identification of an
      amyloidoma localized to the cerebral white matter in a patient who shows no
      evidence of systemic or extracranial localized amyloid deposits. Immunohistologic
      and immunochemical studies, using antibodies against biochemically different
      amyloid fibrils and amyloid-associated proteins, showed reactivity with
      antibodies only to lambda light chain and serum amyloid P-component. Amino acid
      sequence analysis of the purified amyloid fibrils extracted from the brain tumor
      indicates that the amyloid protein is an unusual immunoglobulin lambda light
      chain, starting at residue five of the variable domain. These fibrils consist of
      lambda chain fragments of different lengths (10 to 30 kd) very likely arising by
      polymerization of the amyloid subunit or sequential proteolytic cleavage of the
      light chain, or both. After exposure to denaturing agents, the 10-kd subunit
      retains the characteristics of native amyloid fibrils by electron microscopy.

PMID- 1383874
TI  - Prevalence of non-A non-B hepatitis and anti-HCV antibodies in a Portuguese
      dialysis population.
AB  - Non-A Non-B hepatitis (NANBH) is nowadays one of the most common causes of
      hepatic dysfunction in dialysis patients. We reviewed the records of 231 HBsAg
      negative patients in our unit and found 119 patients with biochemical criteria of
      NANBH (51.5%), 88 of them (68.9%) with circulating antibodies against HCV (chi 2
      P less than 0.0001). Such high prevalence of NANBH was due to an outbreak of
      NANBH in the late 70s and early 80s. Time on haemodialysis (HD) was the major
      risk factor of NANBH in this population, and no other risk factors were
      identified. Prevalence of anti-HCV was similar to reports from non-uraemic
      populations. Anti-HCV seems to be a reliable test to confirm NANBH, but not
      better than using common biochemical criteria of NANBH to manage these patients
      in dialysis units.

PMID- 1383875
TI  - NMDA-induced release of nitric oxide potentiates aspartate overflow from
      cerebellar slices.
AB  - We report that stimulation of neonatal rat cerebellar slices with N-methyl-D
      aspartate (NMDA) release nitric oxide (NO) and also increased the release of
      aspartate. Inhibition of NMDA receptors with the specific antagonist, 3-((RS)-2
      carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) prevented the NMDA-induced
      release of both NO and aspartate. Similar results were obtained with the
      inhibitor of NO synthase, NG-nitroargine (NG-ARG). The NO scavenger, haemoglobin
      prevented the release of aspartate. Under calcium-free conditions NMDA-induced
      aspartate release was abolished and NO release significantly reduced. These
      results indicate that NO has a physiological role in the release of aspartate.

PMID- 1383876
TI  - Pre-spinal convergence between thoracic and visceral nerves of the rat.
AB  - Dichotomizing sensory axons have been demonstrated in a number of species and are
      of significance in understanding the possible mechanisms underlying referred
      pain. The present study reviews work employing fluorescent dyes as tracers to
      demonstrate afferent dichotomization in the peripheral nervous system.
      Dichotomization between the intercostal and splanchnic nerves of the rat was
      demonstrated by means of intraneural transport of Diamidino yellow or Fast blue.
      Frequency of pre-spinal somato-visceral convergence averaged 2% (range 0.1-21%).
      Average frequency of convergence was 8.3% (range 2-23.1%) between internal and
      external intercostal nerves. Control experiments in which axoplasmic transport
      was inhibited by vinblastine ruled out the possibility of errors from non
      axoplasmic transport of the markers. Thoraco-visceral pre-spinal convergence
      occurs in the rat and is variable in extent.

PMID- 1383877
TI  - The origin of trochlear motoneurons in the larval sea lamprey, Petromyzon marinus
      L. An HRP study.
AB  - The origin of trochlear motoneurons in larval lampreys was studied by injection
      of HRP into the orbit. Immature motoneurons had ventricular attachments, the
      position of which with respect to the ventricular sulci was used to study their
      regions of origin. Motoneurons originate from the region between the sulcus
      intermedius dorsalis and the sulcus intermedius ventralis, which in other parts
      of the brain were identified as the visceromotor and viscerosensory columns. Both
      ipsilateral and contralateral immature motoneurons were found. The significance
      of these findings is discussed in relation to the origins of the trochlear nerve
      and its nucleus in vertebrates.

PMID- 1383878
TI  - Dimethyl sulfoxide (DMSO) blocks GABA-induced current in rat dorsal root ganglion
      neurons.
AB  - The effects of dimethyl sulfoxide (DMSO) on gamma-aminobutyric acid (GABA)
      induced Cl- currents of rat dorsal root ganglion neurons in primary culture were
      studied by the whole-cell patch-clamp technique. Bath application of 5 microM
      GABA evoked sustained inward and outward currents at membrane potentials of -60
      mV and +30 mV, respectively, when the external and internal solutions both
      contained 142 mM Cl-. DMSO at concentrations of 0.3-3% (v/v) caused a dose
      dependent inhibition of the inward current induced by 5 microM GABA at -60 mV.
      DMSO at 3% inhibited the GABA-induced inward and outward currents at -60 mV and
      +30 mV to similar extents (54% and 53% of the control, respectively), but the
      time-course of inhibition of the outward current at +30 mV was much faster than
      that of the inward current at -60 mV. These results suggest that DMSO suppressed
      the currents by interacting with GABA receptor-Cl- channel complex protein rather
      than by affecting the lipid-bilayer of the cell membrane.

PMID- 1383879
TI  - Non-uniform distribution of GABA activated chloride channels in cultured cortical
      neurons.
AB  - Several different neurotransmitter receptors and ion channels exist in non-random
      distributions in the membrane of nerve and muscle cells, a pattern which appears
      to have functional implications. The data presented here, based on the
      distribution of single channels in outside-out patches, directly demonstrate that
      receptors for gamma-aminobutyric acid (GABA) and their associated chloride
      channels (GABAA receptors) exist almost exclusively in clusters in the membranes
      of cultured rat cortical neurons. This non-uniform distribution is present both
      in innervated and uninnervated neurons.

PMID- 1383880
TI  - Development of cutaneous and proprioceptive afferent projections in the chick
      spinal cord.
AB  - Muscle and cutaneous nerves were individually labeled with DiI in chick embryos
      to examine the development of sensory afferent arborizations in the spinal cord.
      Initially, cutaneous and muscle arbors were similar; both types first entered the
      spinal gray matter at stage 28-29 (embryonic day (E) 6). Differences in
      projections were first observed by late stage 34 (E8.5): muscle afferent
      collaterals extended almost unbranched to the level of motoneuronal dendrites
      while cutaneous afferents branched frequently and remained within the dorsal
      horn. Projections of putative small caliber axons into laminae 1 and 2, located
      laterally in the chick, did not develop until E13-14.

PMID- 1383881
TI  - Identified septohippocampal neurons survive axotomy: a fine-structural analysis
      in the rat.
AB  - Previous studies have indicated that interruption of the connections between the
      medial septum and hippocampus by cutting the axons results in degeneration and
      death of the projecting septal neurons. However, in these studies cell death has
      been inferred primarily from the loss of immunoreactivity for transmitter
      specific enzymes. In the present study, we labeled septohippocampal projection
      neurons by retrograde tracing and then cut their axons. Subsequent intracellular
      injection of prelabeled cells revealed the morphology of the soma and dendrites
      and allowed us to examine the ultrastructure of these neurons. A large number of
      septohippocampal neurons survived even 10 weeks after axotomy, suggesting that
      axotomized septohippocampal neurons survive for considerable periods beyond the
      time at which they stop expressing transmitter-specific immunoreactivity.
      Survival of axotomized neurons is a prerequisite for pharmacological interference
      aimed at reactivating transmitter expression, axonal re-growth, and the eventual
      reintegration into functionally relevant circuitries.

PMID- 1383882
TI  - The cuneate nucleus in the rat does have an anatomically distinct middle region.
AB  - Recently obtained anatomical evidence supports the division of the rat cuneate
      nucleus (CN) into three rostrocaudal regions, with the middle region receiving a
      disproportionately greater share of the primary sensory input. The CN in the rat
      conforms to the basic rostrocaudal CN pattern described in other mammals,
      including cat, monkey and raccoon.

PMID- 1383883
TI  - Effect of clonidine on the release of serotonin from the rat hippocampus as
      measured by microdialysis.
AB  - The purpose of the present study is to clarify the effect of clonidine on the
      release of serotonin from the rat hippocampus in vivo. For this purpose,
      endogenous serotonin release was measured by brain microdialysis. Potassium
      evoked serotonin release from the hippocampus of freely moving rats was
      significantly inhibited when clonidine (10(-5) M) was added to the perfusion
      solution, while the 5-hydroxyindoleacetic acid output remained unchanged. In
      catecholaminergically denervated rats, clonidine (10(-5) M) also inhibited the
      potassium-evoked serotonin release from the hippocampus and the 5
      hydroxyindoleacetic acid output was unaffected by clonidine. These results
      suggest that the inhibitory effect of clonidine on serotonin release from the
      hippocampus might reflect the activation of alpha 2-adrenoceptors which are
      localized on the serotonergic nerve terminals.

PMID- 1383884
TI  - Topographic projections from the subiculum to the limbic regions of the medial
      frontal cortex in the cat.
AB  - When WGA-HRP was injected into the subicular cortex of the ventral hippocampal
      formation (Hv) in the cat, terminal labeling was seen ipsilaterally in the
      caudoventral parts of the medial frontal cortex: in the infralimbic cortex (area
      25), ventral part of the prelimbic cortex (area 32), and caudoventral part of the
      orbitofrontal cortex (area 12). The terminal labeling was observed in all
      cortical layers except layer 1. The cells of origin of these projections were
      then confirmed to be pyramidal neurons in the subiculum of the Hv. The
      projections were topographically organized: the temporal-septal shift along the
      long axis of the subiculum of the Hv corresponded to a rostroventral-caudodorsal
      shift in the anterogradely labeled limbic regions of the medial frontal cortex.

PMID- 1383885
TI  - Serotonin uptake inhibition: in vivo effect of sertraline in rats.
AB  - Sertraline, a potent and selective serotonin uptake inhibitor, was used to
      analyze the changes occurring in the serotonin system after uptake inhibition in
      vivo. Sertraline (11 mg/kg) lowered extracellular 5-hydroxyindolacetic acid (5
      HIAA), measured in rat hippocampus by in vivo voltammetry, for about 3 h. The
      interaction between sertraline and drugs known to interfere with the release or
      uptake of serotonin (L-5-hydroxytryptophan (5-HTP), d-norfenfluramine and
      tianeptine) was then studied. The sertraline-induced decrease in extracellular 5
      HIAA was related to the inhibition of uptake.

PMID- 1383886
TI  - Experimental peripheral neuropathy decreases the dose of substance P required to
      increase excitatory amino acid release in the CSF of the rat spinal cord.
AB  - Partial ligation of the sciatic nerve of rats produces hyperalgesia similar to
      that seen in humans following nerve injury. In this study, we used microdialysis
      of the spinal cord cerebral spinal fluid (CSF) to test the hypothesis that
      hyperalgesia is due to an enhanced release of excitatory amino acids (EAA) in
      response to substance P (SP). Intrathecal SP caused release of aspartate and
      glutamate in the CSF of rats with partial sciatic ligation at a dose of SP that
      did not cause release in sham operated animals. Neonatal capsaicin pretreatment
      blocked SP-induced EAA release in both sham and sciatic ligated animals. Release
      of EAAs in ligated animals was not significantly different from release in sham
      operated animals following higher doses of SP or chemical nociceptive
      stimulation. These results demonstrate a partial sciatic ligation-induced
      decrease in the dose of SP required to initiate EAA release in the CSF of the
      spinal cord, a change which could play an important role in hyperalgesia.

PMID- 1383887
TI  - Vocalization and marked pressor effect evoked from the region of the nucleus
      retroambigualis in the caudal ventrolateral medulla of the cat.
AB  - It is well established that the nucleus retroambigualis (NRA) of the cat contains
      a population of expiratory-related neurons. We report here that in the
      unanesthetized, decerebrate cat, microinjections of 300-900 pmol of D,L
      homocysteic acid within the NRA evoked excitation of laryngeal as well as
      expiratory muscles, and often pressor responses. Moreover, vocalizations, which
      did not sound like normal feline vocalizations (i.e., hiss, howl, mew, growl),
      were evoked from a restricted region of the NRA, 1-3 mm caudal to the obex. The
      results indicate that in addition to its role in expiration: (i) the NRA plays an
      important role in the control of laryngeal muscles and the production of
      vocalization; and (ii) that neurons in the NRA region can modulate arterial
      pressure.

PMID- 1383888
TI  - Regional cerebral protein synthesis after transient ischemia in the rat: effect
      of the AMPA antagonist NBQX.
AB  - Normothermic rats with 12 min, complete cerebral ischemia were treated with the
      AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxalinedione
      (NBQX) [10], which prevents CA1 pyramidal neuron loss. Twenty hours after
      ischemia, cerebral protein synthesis rate (CPSR) was measured
      autoradiographically using [35S]methionine. Ischemia caused a 38% decrease of
      CPSR in CA1, and postischemic treatment with NBQX caused a 66% decrease in this
      region. Also treatment with NBQX alone resulted in a decrease (22% in CA1) of the
      CPSR. Since some evidence exists that the neuroprotective effect of NBQX is
      related to blockade of the fast AMPA-mediated transmission, the further decrease
      of the postischemic CPSR in CA1 could be a mere side effect.

PMID- 1383889
TI  - Autoradiographic localization of [125I]charybdotoxin binding sites in rat brain.
AB  - Charybdotoxin, a 37 amino acid peptide isolated from scorpion venom, is a potent
      inhibitor of potassium channel function. [125I]charybdotoxin was originally
      believed to be a selective ligand for the Ca(2+)-sensitive channel in many
      tissues, but it appears to bind only to a voltage-sensitive potassium channel in
      brain. We found high densities of [125I]charybdotoxin binding in lateral
      olfactory tract, interpeduncular nucleus and a variety of mesencephalic nuclei.
      Moderate levels were found in the cerebral cortex, medial thalamus, hypothalamus
      and selected thalamic nuclei. These results indicate that [125I]charybdotoxin
      identifies a potassium channel or channels with a unique distribution in the
      brain.

PMID- 1383890
TI  - Galanin and bethanechol appear to activate the same inwardly rectifying potassium
      current in mudpuppy parasympathetic neurons.
AB  - Galanin- and bethanechol-activated whole cell currents were studied in
      dissociated mudpuppy parasympathetic neurons kept in 12.5 mM KCl. The bethanechol
      induced current was reduced when generated during a galanin-induced current. The
      galanin and bethanechol currents reversed at -45 mV and exhibited inward
      rectification at more negative potentials. Both the galanin- and bethanechol
      induced current relaxations recorded during negative voltage steps were fitted
      best by two exponentials with the averaged time constant values not significantly
      different for the galanin and bethanechol currents. We conclude that galanin and
      bethanechol activate a similar membrane potassium conductance which is different
      from the background potassium conductance.

PMID- 1383892
TI  - Chemical identification and morphological characterization of the inferior olive
      in the frog.
AB  - Tritiated D-aspartate was injected into the cerebellar cortex of grassfrogs, Rana
      temporaria. Retrograde labeling was observed in a cell column of the
      contralateral caudal medulla, but not in other areas known to give rise to
      cerebellar mossy fibers. The aspartate-positive neurons are therefore considered
      to represent the origin of cerebellar climbing fibers in the inferior olive, as
      reported earlier for rat and turtle by other investigators. Contrary to earlier
      reports we found no extraolivary climbing fibers in the VIIIth nerve and in
      Scarpa's ganglion. Our results support the view that the climbing fiber system of
      vertebrates is anatomically, physiologically and chemically very distinct and
      phylogenetically very conservative.

PMID- 1383891
TI  - The effect of chronic clozapine on basal dopamine release and apomorphine-induced
      DA release in the striatum and nucleus accumbens as measured by in vivo brain
      microdialysis.
AB  - Previous studies have produced conflicting results concerning the effect of
      chronic oral vs. parenteral (i.p.) clozapine administration on dopamine (DA)
      release and metabolism in the striatum and nucleus accumbens (n. accumbens) of
      freely moving rats using in vivo microdialysis. In this study, parenteral chronic
      clozapine (20 mg/kg/day for 21 days, i.p.) had no effect on basal DA release and
      metabolism in either region. Chronic treatment with parenteral clozapine also did
      not reverse the decrease in DA release and metabolism in striatum and n.
      accumbens produced by apomorphine (100 micrograms/kg, s.c.). These results differ
      significantly from a previous report following i.p. clozapine and confirm the
      results previously reported with oral clozapine.

PMID- 1383893
TI  - The GABAA receptor complex in experimental absence seizures in rat: an
      autoradiographic study.
AB  - The regional distribution of radioactive ligand binding for different receptors
      of the gamma-aminobutyric acid A (GABAA)-benzodiazepine-picrotoxin chloride
      channel complex was measured on tissue section by autoradiography in brains taken
      from a genetic strain of Wistar rats with spontaneous absence-like seizures, the
      genetic absence epilepsy rats from Strasbourg (GAERS), and a control colony. The
      ligands employed included [3H]muscimol for high affinity GABA agonists sites;
      [3H]SR 95531 for the low-affinity GABA sites; [3H]flunitrazepam for the
      benzodiazepine sites; and [35S]t-butyl bicyclophosphorothionate (TBPS) for the
      picrotoxin site. There was no significant change between GAERS and control
      animals in [3H]flunitrazepam and [35S]TBPS binding. However, there was
      significantly decreased [3H]muscimol and [3H]SR 95531 binding in the CA2 region
      of the hippocampus of the GAERS. This was due to a decrease in Bmax of both
      [3H]muscimol and [3H]SR 95531 binding in the epileptic strain.

PMID- 1383894
TI  - HT7, Neurothelin, Basigin, gp42 and OX-47--many names for one developmentally
      regulated immuno-globulin-like surface glycoprotein on blood-brain barrier
      endothelium, epithelial tissue barriers and neurons.
AB  - The antigens HT7 and Neurothelin were recently described as inducible membrane
      glycoproteins on chick blood-brain barrier endothelium. Our results demonstrate
      that the Neurothelin antibody 1W5 does recognize the isolated HT7 protein as well
      as the HT7 protein expressed by COS-1 cells transfected with the HT7 cDNA.
      Therefore, the HT7 and Neurothelin epitopes can be found on an unique
      glycoprotein. By low stringency hybridization we have isolated the murine cDNA
      clone encoding the homologous murine protein. The nucleotide sequence of the open
      reading frame is identical to that of the cDNA clones encoding the gp42 protein
      and the Basigin antigen expressed in F9 cells and in the early mouse embryo. The
      murine amino acid sequence shows 94% identity with the rat OX-47 membrane
      glycoprotein which was shown to be expressed in blood-brain barrier endothelium
      and several epithelial cell layers. These results demonstrate that HT7,
      Neurothelin, gp42, Basigin and OX-47 are different names for probably the same
      glycoprotein in different species.

PMID- 1383895
TI  - Changes in striatal dopamine release and metabolism during and after subchronic
      haloperidol administration in rats.
AB  - The release and metabolism of dopamine (DA) in the striatum of rats during and
      after subchronic haloperidol (HAL) administration (3 weeks) was assessed using in
      vivo microdialysis. Basal extracellular levels of DA, DA metabolites
      (homovanillic acid and 3,4-dihydroxyphenylacetic acid) and the serotonin
      metabolite (5-hydroxyindoleacetic acid) were not significantly different from
      control values at 3 weeks of HAL administration and 3 days after drug withdrawal.
      The specific DA D2 receptor antagonist, raclopride (0.5 mg/kg, i.p.),
      significantly increased DA release and metabolism in control animals, but
      decreased DA release in the HAL-treated groups at 3 weeks of drug treatment. This
      effect was not significant following drug withdrawal. These results contrast with
      our previous finding that chronic HAL treatment (32 weeks) increases basal DA
      metabolism and further support the possibility that changes in DA function differ
      following short term vs. long term neuroleptic exposure.

PMID- 1383896
TI  - Influence of electro-acupuncture on the release of substance P and the potential
      evoked by tooth pulp stimulation in the trigeminal nucleus caudalis of the
      rabbit.
AB  - The effects of electro-acupuncture (EAP) on the release of substance P (SP) and
      the responses evoked by tooth pulp stimulation (ST) in superficial layers of the
      trigeminal nucleus caudalis (Vc-I,II) were studied in rabbits. ST evoked increase
      in release of immunoreactive SP (iSP). This increase was inhibited by EAP in 9 of
      13 animals. The potentials evoked by ST were composed of two main components with
      latency times of ca 4.3 msec and ca. 9.4 msec. The latter component, reflecting
      the excitation of A delta fibers, was significantly inhibited by CP-96,345 (3
      mg/kg, i.v.), an SP antagonist. EAP also inhibited the latter component in 8 of
      11 animals. These results suggest that one of the mechanisms of analgesia induced
      by EAP is inhibition of stimulus-evoked SP release in the Vc-I,II.

PMID- 1383897
TI  - A heparin-binding protein in porcine seminal plasma stimulates neurite outgrowth
      on neuroblastoma cells in culture.
AB  - A protein of neurite outgrowth activity has been identified in porcine seminal
      plasma after ammonium sulfate precipitation and affinity chromatography on
      heparin-Sepharose. Upon SDS-PAGE, the polypeptide is shown to have a M(r) of
      16,000-18,000. Biologically by induction of neuritic processes on neuroblastoma
      cells, and immunologically by cross-reaction with specific antisera, this seminal
      plasma protein differs from acidic fibroblast growth factor (aFGF), basic
      fibroblast growth factor (bFGF) and nerve growth factor (NGF). The neurite
      outgrowth activity is relatively stable at pH 3-7 and under denaturing conditions
      of 8 M urea and beta-mercaptoethanol, but is inactivated by treatment of trypsin.
      This appears to be a novel protein, enhancing morphological differentiation of
      neuroblastoma cells in culture.

PMID- 1383898
TI  - Estimating the time of death in stillborn fetuses: I. Histologic evaluation of
      fetal organs; an autopsy study of 150 stillborns.
AB  - OBJECTIVE: To determine whether the autopsy histology of fetal tissues can
      determine the time of death of stillborn fetuses. METHODS: Hematoxylin and eosin
      slides from autopsies of 150 stillborn fetuses with well-timed deaths were
      evaluated retrospectively. Fetuses were divided into a learning set (100 fetuses)
      and a test set (50 fetuses). RESULTS: From assessment of the 100 fetuses in the
      learning set, 23 histologic features were identified with possible temporal
      associations with fetal death. When those histologic features were randomly and
      blindly assessed in the 50 test fetuses, ten features performed well as
      diagnostic tests (sensitivity, specificity, and positive predictive values at or
      above 0.875), correctly classifying 43 of 50 fetuses (86%) with respect to the
      time of death. The ten histologic features and their predicted death-to-delivery
      intervals were: loss of nuclear basophilia in individual cells in renal cortical
      tubules (4 hours), liver (24 hours), inner half of the myocardium (24 hours),
      outer half of the myocardium (48 hours), bronchial epithelium (96 hours), and
      tracheal cartilage (1 week); and loss of nuclear basophilia of all cells in the
      liver (96 hours), gastrointestinal tract (1 week), adrenal (1 week), and kidney
      (4 weeks). The development of these histologic changes appeared to be accelerated
      by fetal hydrops and a delivery-to-autopsy interval exceeding 24 hours and
      decelerated by fetal gestational age under 25 weeks. CONCLUSION: Histologic
      changes identifiable in hematoxylin and eosin-stained fetal tissue may be useful
      for estimating the time of death in many stillborn fetuses.

PMID- 1383899
TI  - Placenta accreta/percreta/increta: a cause of elevated maternal serum alpha
      fetoprotein.
AB  - OBJECTIVE: To investigate the relationship between elevated maternal serum alpha
      fetoprotein (MSAFP) and abnormal placental adherence (placenta
      accreta/percreta/increta). METHODS: We reviewed the MSAFP levels of 11 women who
      had cesarean hysterectomies because of placenta accreta/percreta/increta. The
      control group consisted of 14 women who delivered by cesarean because of placenta
      previa but who had no abnormal placental adherence. RESULTS: Five of the 11 women
      with placenta accreta/percreta/increta had elevated MSAFP, whereas all 14
      controls had normal levels. CONCLUSION: These results indicate a significant
      association between elevated MSAFP and placenta accreta/percreta/increta (P =
      .017). Patients with an unexplained elevation of MSAFP as well as placenta previa
      may be at increased risk for abnormal placental adherence.

PMID- 1383900
TI  - Low birth weight and preterm delivery in relation to early-gestation vaginal
      bleeding and elevated maternal serum alpha-fetoprotein.
AB  - OBJECTIVE: To determine whether early-gestation vaginal bleeding and elevated
      maternal serum alpha-fetoprotein (MSAFP) are independent risk factors for adverse
      infant outcomes. METHODS: We conducted a cohort study of 201 women with an
      elevated MSAFP (at least 2.0 multiples of the median [MOM]) and a second
      trimester ultrasound evaluation at Swedish Hospital Medical Center between
      January 1989 and March 1991, and 211 women with MSAFP levels below 2.0 MOM who
      had also undergone ultrasound evaluations during the same period. RESULTS:
      Stratified analyses demonstrated that early-gestation bleeding and elevated MSAFP
      were independent risk factors for the delivery of both preterm and low birth
      weight infants. Compared with women with no history of early-gestation bleeding
      or elevated MSAFP, women with early-gestation bleeding alone had a relative risk
      (RR) of preterm delivery of 4.3 (95% confidence interval [CI] 1.5-12.1); non
      bleeders with elevated MSAFP had an RR of 4.6 (95% CI 1.9-10.9). A combined
      history of early-gestation bleeding and elevated MSAFP was associated with an
      almost sixfold increased risk of preterm delivery (RR 5.8; 95% CI 2.2-15.6).
      Analyses restricted to women with normal-appearing appearing placentas by second
      trimester ultrasound evaluations yielded similar results. CONCLUSIONS: These
      findings support an earlier report documenting the independence of early
      gestation bleeding and elevated MSAFP as predictors of adverse infant outcomes.

PMID- 1383901
TI  - Effect of dextran on predamaged corneal endothelium: an organ culture study.
AB  - Dextran T500 was used as a supplement in organ culture medium to evaluate its
      effect on corneal endothelium with disseminated damage. After 1 week of
      culturing, the control group showed an intact endothelium throughout the entire
      cornea. However, in the dextran-supplemented group, multiple endothelial necroses
      were observed in 5 of 10 corneas. Besides, intracytoplasmic vacuoles and
      granules, deposits on the endothelial surface and widened intercellular spaces
      were quite numerous. The potential toxicity of dextran to degenerated corneal
      endothelial cells may be responsible for these findings.

PMID- 1383902
TI  - [Comparative study of advanced-stage Hodgkin's lymphoma patients treated with
      either COPP or ABVD drug combinations].
AB  - Between January 1985 and March 1988, 45 patients with advanced Hodgkin's disease
      were randomly assigned to receive either COPP (22 patients) or ABVD (23
      patients). 9 and 16 patients achieved complete remission in the COPP and ABVD
      groups, respectively. One of the complete responders (COPP) relapsed during the
      follow-up. Patients treated with COPP experienced myelosuppression and
      neurotoxicity more frequently whereas alopecia and gastrointestinal symptoms were
      observed among those receiving ABVD. Present data confirm the favorable impact of
      primary ABVD treatment in advanced Hodgkin's disease.

PMID- 1383903
TI  - [The use of endoprostheses (stents) in airway stenosis].
AB  - Six patients with obstruction of the trachea were treated with silicone rubber
      endothracheal stents implanted with flexible bronchoscope. In every case the
      stent caused significant clinical improvement of the ventilation. At the
      postintubation stenosis the stent can result a final recovery, at the malignant
      processes the implantation seems to be a new palliative method.

PMID- 1383904
TI  - [Secondary acute leukemia in Hodgkin's disease].
AB  - Two secondary acute leukaemias out of 166 patients with Hodgkin's disease were
      detected. At a young female patient treated only with chemotherapy the acute
      leukaemia developed 39 months following the diagnosis of Hodgkin's disease.
      Phenotype of leukaemic blast cells could not be determined exactly. After a short
      complete remission (1,5 month) the patient died because of the progression of her
      leukaemic process. The other young male patient treated with radio- and
      chemotherapy had six years disease free interval between the diagnosis of two
      malignant diseases. The combined cytostatic treatment of his acute lymphoblastic
      leukaemia resulted complete remission that lasted for one year but later the
      progression of leukaemia caused death. In connection with these cases the authors
      reviewed the current questions of treatment related acute leukaemias in Hodgkin's
      disease.

PMID- 1383905
TI  - [Implantation of a Stecker metal prosthesis in malignant stenosis of the gastric
      stump].
AB  - A 55 year old patient 3 years after gastric resection (Billroth II) has got
      gastric outlet stenosis. Half year ago was established a tumour recidive, that
      the time of reoperation was inoperable. Under endoscopic and radiological control
      we have introduced and placed a 19 mm diameter, 4 cm long balloon expandable
      tantalum stent (Strecker stent). The gastric passage has normalised and after 6
      month the patient is symptom free.

PMID- 1383906
TI  - [Correlation between elevated maternal serum alpha-fetoprotein, certain pregnancy
      complications and fetal death].
AB  - In a prospective epidemiological study of 23,792 singleton pregnancies the
      authors investigated the relationship between elevated maternal serum alfa
      fetoprotein level and the risk of pathological pregnancy outcome. It has been
      found that elevated level of maternal alfa-fetoprotein (above 2.5 MoM) is
      associated with a higher risk of pathological pregnancies and an increased risk
      of subsequent fetal death. Physicians should be aware of the benefits of the
      maternal alpha-fetoprotein screening not only in the context of prenatal
      detection of congenital defects, but also in early identification of increased
      risk of certain obstetric complications.

PMID- 1383907
TI  - [Initial results of hybrid chemotherapy of Hodgkin's disease using COPP/VBA].
AB  - 19 patients with advanced, previously untreated Hodgkin's disease were treated
      with COPP/ABV (cyclophosphamide, vincristine, procarbasine, prednisolone,
      adriamycin, bleomycine, vinblastine) hybrid regimen. Complete response was
      achieved in 8 patients, partial response in 9 patients and primary treatment
      failure occurred in 2 patients. Two patients received involved field irradiation
      for the residual disease. 17 months after finishing the therapy one of the
      complete responders suffered a relapse. Of the 8 partial responders, 5 patients
      relapsed. 2 relapses occurred during the treatment and 3 relapses were observed
      in the first 7 months of follow-up. 2 of the partial responders and both
      nonresponders succumbed to their disease. There were no serious side effects and
      treatment-related death did not occur.

PMID- 1383909
TI  - An overview of molecular biology in otolaryngology.
AB  - The molecular biology revolution is just beginning to bear fruit in medicine.
      This is an exciting time to be active in the field of biomedical research. It is
      also an exciting time for clinicians, watching the applications of our new-found
      knowledge to clinical specialties.

PMID- 1383908
TI  - Overexpression of the A9 antigen/alpha 6 beta 4 integrin in head and neck cancer.
AB  - A tumor-associated antigen detected by monoclonal antibody UM-A9 raised against a
      cultured cell line from a patient with an aggressive SCC of the oral cavity has
      been defined. The A9 antigen is abnormally expressed in squamous cancers, with
      loss of basal polarization and increased intensity of expression distinguishing
      malignant from normal cells. A minority of cultured SCC cell lines and about one
      third of fresh tumors exhibit polarized A9 expression. The increased intensity
      and loss of polarized expression of A9 antigen in recurrent and metastatic tumor
      cell lines when compared with primary or early tumor cell lines from the same
      patients indicated an association of altered expression with tumor progression.
      When A9 expression was evaluated in frozen tumor sections, three patterns of
      expression representing increasing intensity and loss of polarization were
      observed. Patients whose tumors exhibited the most intense A9 antigen expression
      had a higher rate of early relapse than patients whose tumors exhibited low
      intensity and polar expression. Loss of blood group antigen expression was also
      associated with poor prognosis, and together high A9 antigen expression and loss
      of blood group defined a group of patients at high risk of early relapse. The A9
      antigen is immunologically and biochemically identical to the alpha 6 beta 4
      integrin. The association of high expression of the A9/alpha 6 beta 4 integrin as
      a prognostic factor is supported by similar findings with a mouse model system.
      The mouse tumor-associated antigen, TSP-180, which is also an alpha 6 beta 4
      integrin, distinguishes highly metastatic tumor cells from nonmetastatic variants
      of the same tumor line. In SCC, the alpha 6 beta 4 integrin contributes to
      attachment to laminin since anti-alpha 6 subunit specific antibody blocks cell
      attachment and only the beta 4 subunit is found in association with the alpha 6
      subunit in these cells. Similar findings were obtained in colon carcinomas.
      Antibodies and peptides that block laminin attachment may lead to the development
      of antimetastatic agents for squamous carcinomas. The beta 4 subunit is unique
      from other integrins in that it has an unusually long cytoplasmic domain, the
      function of which is not known. The beta 4 subunit is heavily phosphorylated
      under conditions that favor anchoring and terminal differentiation in normal
      keratinocytes. Paradoxically the beta 4 subunit is also heavily phosphorylated in
      tumor cells, which are highly migratory and immortalized.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1383910
TI  - [Investigations of the ototoxicity of dicortinef (ear drops)].
AB  - The authors investigated the ototoxic influence of Dicortinef in laboratory
      animals. Their examinations were performed on 15 guinea pigs (weighing 210-380
      g.) after application of this medicine to the fenestra rotunda. The harmful
      effect of Dicortinef was expressed by the characteristic fall in the microphonic
      potential (PM) and potential of the acoustic nerve (AP).

PMID- 1383911
TI  - Cardiac function in obstructive sleep apnea patients following
      uvulopalatopharyngoplasty.
AB  - Obstructive sleep apnea syndrome (OSAS) is associated with severe cardiac
      arrhythmias and conduction abnormalities. Cor pulmonale and right-sided heart
      failure may ensue. Uvulopalatopharyngoplasty (UPPP) is one of several treatment
      modalities suggested for OSAS. Tracheotomy and CPAP treatment in adult OSAS
      patients and adenotonsillectomy in children with OSAS were shown to lead to
      improvement in some cardiac parameters. Cardiac function was prospectively
      evaluated in 19 OSAS patients before and after UPPP. No significant changes after
      surgery were noted on electrocardiographic studies. Improvement in global and
      regional function of both ventricles was seen in 91% of the patients. A trend
      toward significant elevation in left ventricular ejection fraction and a
      statistically significant increase in right ventricular ejection fraction were
      observed (45% +/- 9% to 50% +/- 7% [p = 0.007]). Our results support performance
      of UPPP in selected OSAS patients for relief of potentially life-threatening
      cardiac pathologies.

PMID- 1383912
TI  - The establishment of human T cell lines reactive with specific periodontal
      bacteria.
AB  - Human T cell lines (TCLs) were obtained by stimulation of peripheral blood
      mononuclear cells (PBMCs) with the 2 periodontopathic bacteria, Porphyromonas
      gingivalis FDC-381 and Fusobacterium nucleatum FDC-263. After the first round of
      stimulation and rest, the cells responded specifically to the bacteria originally
      used to establish each line. Throughout the culture period, the responsiveness of
      each of the TCLs to their specific bacteria increased. Phenotypic analysis of the
      TCLs revealed heterogeneity of cell types. In both TCLs approximately 80% of the
      cells were T cells, all of which bore the alpha beta T cell receptor. The P.
      gingivalis-reactive TCL (PG-TCL) showed approximately equal proportions of CD4+
      and CD8+ cells, whereas the F. nucleatum-reactive TCL (FN-TCL) was predominantly
      CD4+. The expression of CD25, HLA-DR, CD45RA and CD29 on these CD4+ cells varied
      throughout the culture period of 45 days. These results demonstrate that it is
      possible to establish long-term T cell lines reacting to specific
      periodontopathic bacteria.

PMID- 1383914
TI  - Hepatitis C core antibody detection in acute hepatitis and cirrhosis patients
      from Tunisia.
AB  - The detection of anti-Hepatitis C virus (HCV) Core antibodies is an important
      addition to HCV antibody testing. In this study it appears to be more specific
      than the first generation HCV tests and in combination with the detection of anti
      C33c antibodies, it is possibly more sensitive. In Tunisia hepatitis C virus is
      implicated by the presence of anti-Core antibodies in only 8% of the adult cases
      of acute hepatitis as opposed to 60% for Hepatitis B virus (HBV) and 4% for
      Hepatitis A virus (HAV). In contrast to the low prevalence of HCV infection among
      acute hepatitis cases, HCV infection is implicated in 35% of the cirrhosis cases.
      These results stress the potential importance of HCV infection in the development
      of cirrhosis which is a relatively common disease in North Africa.

PMID- 1383913
TI  - [Treatment of HIV infection: perspectives].

PMID- 1383915
TI  - [Cytokeratins, markers of epithelial cell differentiation: expression in normal
      epithelia].
AB  - Intermediate filaments, the most stable of cytoskeleton components, are extremely
      diverse and usually correlate with the histological subtype since in nearly all
      cell types a single type of intermediate filament (IF) is found. The
      cytokeratins, which are specific of epithelia, are the largest and most diverse
      class of intermediate filaments. Twenty different cytokeratin polypeptides have
      been identified in humans and separated on the basis of isoelectrical pH and
      apparent molecular weight using two-dimensional electrophoresis. These data have
      been used to establish a cytokeratin catalogue which currently serves as a
      reference [43, 48]. The number of cytokeratin polypeptides expressed ranges from
      2 to 5 for each epithelial cell and from 2 to 10 for each epithelium and even of
      each cell layer within a given epithelium. A broad spectrum of anticytokeratin
      antibodies with subgroup or single polypeptide specificity is currently
      available. The distribution of cytokeratins in normal epithelia is reviewed
      herein and commercially available anti-cytokeratin antibodies are listed.

PMID- 1383916
TI  - [Expression of cytokeratins during embryogenesis and in pathologic epithelia].
AB  - Epithelial cell intermediate filaments, or cytokeratins, are excellent markers
      for cell differentiation. During embryogenesis, cytokeratins specific of a stage
      of differentiation step always become detectable before corresponding morphologic
      changes: for instance, cytokeratins 5 and 14 are found around the eight week,
      shortly before stratification of the epithelium occurs, and cytokeratins 1 and 10
      are produced before morphologic evidence of keratinization becomes detectable.
      Among potential diagnostic applications, analysis of cytokeratin patterns of
      epidermal cells desquamated in the amniotic fluid may provide earlier and less
      invasive diagnosis than fetoscopic biopsies. Similarly, a review of cytokeratins
      expressed in a variety of epithelial diseases (involving the epidermis, digestive
      tract, respiratory tract, urogenital tract, or breast) demonstrated persistence
      of the original tissue pattern in some instances (this was the case for the
      majority of simple epithelia) but not in others (complex epithelia). This
      suggests that cytokeratins may prove valuable as markers for specific tumor
      stages or types and may provide earlier information than morphologic studies.

PMID- 1383917
TI  - Mutations within the S gene of hepatitis B virus transmitted from mothers to
      babies immunized with hepatitis B immune globulin and vaccine.
AB  - A variant of hepatitis B virus (HBV) having a specific mutation within the S gene
      has been found to infect vaccinees. To know whether similar variants were
      involved in Japan, we analyzed two cases of maternal transmission of HBV in
      infants immunized with hepatitis B immune globulin and hepatitis B vaccine. DNA
      clones of HBV S genes were propagated from patients and family members and
      sequenced. In one family, the DNA clones from the baby patient had a Gly-to-Arg
      mutation at the 145th codon of the S gene, whereas those from her mother had no
      such mutations. In the other family, all the DNA clones obtained from the two
      infected children had the 145th codon intact, but they had a missense mutation at
      the 126th codon of the S gene, causing an amino acid substitution of Asn for Thr
      or Ile. This same mutation was observed in 12 of 17 clones of DNA obtained from
      their mother. In comparison with the wild type HBV-derived hepatitis B surface
      antigen, the two types of S gene mutations, either at the 145th or the 126th
      codon, were associated with a significant decrease in the antigenicity of some
      determinants on the hepatitis B surface antigen, measured by MAb. Amino acid
      substitution at these sites, therefore, would have induced the escape from
      conventional vaccines that were S gene products of wild type HBV and also from
      hepatitis B immune globulin, whose main components were probably also antibodies
      against the S gene products expressed by wild type HBV.

PMID- 1383918
TI  - The in vitro effects of stem cell factor and PIXY321 on myeloid progenitor
      formation (CFU-GM) from immunomagnetic separated CD34+ cord blood.
AB  - Two novel cytokines, stem cell factor (SCF) and PIXY321 (a fusion protein,
      granulocyte macrophage colony-stimulating factor+IL-3), have recently been
      demonstrated to enhance in vitro adult myelopoiesis. In this study, we compared
      the success of separating very early hematopoietic progenitor cells (CD34+) from
      both cord blood (CB) and adult bone marrow (ABM) and their differential response
      to SCF, PIXY321, and other later-acting colony-stimulating factors (CSF).
      Briefly, CD34+ cells were isolated from CB and ABM with an anti-CD34 MAb, HPCA-1,
      and incubated with various combinations of SCF, PIXY321, and other CSF. The
      percentage of CD34+ cells was decreased in CB compared to ABM before separation
      (0.54 versus 1.71%) (p = 0.05). Isolated CD34+ cells from CB and ABM were similar
      in lineage with respect to CD38, HLA-DR, CD33, and CD5, but decreased in CB with
      respect to B-lineage expression (CD19, CD10, and CD22) (p = 0.05). SCF increased
      colony forming unit-granulocyte-macrophage (CFU-GM) formation from CB CD34+ cells
      compared to unconditioned media and had a significant additive increase with IL-3
      (p = 0.006) and granulocyte colony-stimulating factor (p = 0.03). SCF also had an
      additive increase in CB CFU-GM formation with PIXY321 (p = 0.007). PIXY321 had a
      similar increase in CFU-GM formation from both CB and ABM CD34+ cells compared to
      the combination granulocyte macrophage colony-stimulating factor + IL-3. When SCF
      was added to IL-3, PIXY321, or PIXY321 + IL-6, there was an increase in CFU-GM
      from CB versus ABM CD34+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383919
TI  - Biology and clinical applications of hemopoietins in pediatric practice.

PMID- 1383920
TI  - Population-based study of the incidence, complexity, and severity of neurologic
      disability among survivors weighing 500 through 1250 grams at birth: a comparison
      of two birth cohorts.
AB  - Mortality and incidence, complexity, and severity of early childhood
      neurodevelopmental disability are reported for two cohorts of preterm infants of
      500 through 1250 g birth weight. Comparing 1978-1979 (cohort 1) and 1988-1989
      (cohort 2), 1-year survival improved from 82 (36%) of 226 to 197 (67%) of 291.
      Cohort 1 survivors were heavier and more mature than cohort 2 survivors (1047 g
      vs 930 g, 29.6 vs 27.3 weeks). Parental demographic variables were similar. The
      incidence of specific disabilities with greater than 97% follow-up to 1.5 years
      adjusted age did not change: cerebral palsy, 14 (17%) vs 20 (10%); vision loss, 5
      (6%) vs 9 (5%); mental retardation, 9 (11%) vs 13 (7%); hearing loss, 3 (4%) vs 7
      (4%); and convulsive disorders, 2 (2%) vs 3 (2%). The overall number of disabled
      children (17 [21%] vs 30 [15%]), complexity of disability (> or = 2 disabilities
      per child: 11 [13%] vs 10 [5%]), and severity of disability (projected
      dependency: 6 [7%] vs 10 [5%]) did not differ between cohorts 1 and 2. The
      cerebral palsy prevalence, based on neonatal survival, dropped from 157 per 1000
      to 93 per 1000. Analysis by birth weight-specific categories in 250-g increments
      did not alter results, but disability rates were highest for those of lowest
      weight. In contrast to other reports this population-based North American study
      from a well-developed perinatal regional program reports no increase in
      incidence, complexity, or severity of disability in preterm infants weighing 500
      through 1250 g at birth.

PMID- 1383922
TI  - [Pregnancy in insulin-dependent diabetic patients].
AB  - There has been a dramatic reduction in perinatal mortality and the incidence of
      malformation among the offspring of mothers with IDDM, current perinatal infant
      mortality now being no worse among mothers treated at the best Scandinavian
      diabetes centres than among non-diabetic mothers (Table 1). Such improvement is
      dependent upon very well organised care facilities and information services,
      close cooperation with the diabetic gravida, and the availability of good medical
      treatment that does not unduly burden her economy. Among diabetic women, careful
      planning for pregnancy improves the chances of giving birth to healthy offspring.

PMID- 1383921
TI  - cAMP and Ca2+ act co-operatively on the Cl- conductance of HT29 cells.
AB  - Previous studies in HT29 cells have revealed that the Cl- channels induced by
      cAMP or by increasing cytosolic Ca2+, e.g. by addition of ATP, and by hypotonic
      cell swelling share in common all examined properties, such as ion selectivity
      and blocker sensitivity. In addition, it was shown that conductances induced by
      either pathway were not additive. Therefore all three pathways apparently act on
      the same type of small conductance Cl- channel. In CFPAC-1 cells the general
      properties of the Cl- conductance were identical. However, the cAMP response was
      absent. In both cell types the Ca(2+)-mediated conductance response was
      transient. Here we examine the kinetics of the conductance increases induced by
      neurotensin (NT, 10(-8) mol/l) or ATP (10(-5) mol/l) in HT29 and CFPAC-1 cells
      using the slow (nystatin) or fast whole cell patch clamp technique, and we ask
      whether cAMP influences these kinetics. In the continuous presence of NT the
      conductance response in both cell types was very transient. It collapsed with a
      time constant (tau) of 39 (30-56 s) in HT29 and of 33 (27-41 s) in CFPAC-1 cells.
      The ATP response was also transient with a tau of 49 (42-57 s) in HT29 cells and
      102 (77-152 s) in CFPAC-1 cells. Pre-treatment by membrane permeable cAMP (10(-3)
      mol/l) enhanced the baseline conductance in HT29 but not in CFPAC-1 cells.
      Furthermore, the ATP- and NT-induced conductance increases became significantly
      less transient in HT29 but not in CFPAC-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383923
TI  - Competitive binding of a monoclonal antibody SZ-21 with anti-PLA1 antibodies and
      its potential for clinical application.
AB  - Both intact IgG and Fab fragments of a monoclonal antibody SZ-21, directed
      against platelet glycoprotein (GP) IIIa, inhibited binding of anti-PLA1
      antibodies to PLA1-positive platelets in a dose dependent manner. Conversely, the
      binding capacity of the platelets for SZ-21 was decreased in the presence of anti
      PLA1 antibodies. In Western blots, the determinant for SZ-21 was present on
      GPIIIa from either PLA1 or PLA2 homozygotes, but SZ-21 did not affect the
      interaction of anti-Yukb alloantibodies with their target antigen on GPIIIa.
      These results suggest that SZ-21 reacts with an epitope on the GPIIIa molecule
      very close to but not identical with that for anti-PLA1. The existence of PLA1
      reactive alloantibodies in serum could be demonstrated by their competitive
      effect on the binding of SZ-21.

PMID- 1383924
TI  - Hodgkin's disease, clinical stages I, II A-B and IIIA. Results of brief
      chemotherapy followed by irradiation.
AB  - From October 1980 to September 1985, 152 patients with Hodgkin's disease (HD) in
      clinical stages (CS) I, II A-B and IIIA were treated with combined modality
      therapy (CMT): brief chemotherapy (CT) followed by radiotherapy (RT). CS IA and
      IIA cases received 3 cycles of MOP, while CS IB, IIB and IIIA cases were randomly
      assigned to receive MOP or MOP alternating with ABVD (4 cycles). Irradiation was
      delivered according to the areas initially involved and response to CT. CS I and
      II subjects in complete remission (CR) received localized fields, whereas CS I,
      II and IIIA subjects in partial remission (PR) received extended fields, with
      subtotal nodal RT for CS I and II and CS IIIA without pelvic involvement and
      total nodal RT for CS I and II below diaphragm and CS IIIA with pelvic
      involvement. Following CT, CR was 60% (IA-IIA: 71.5%, IB-IIB: 37%, IIIA: 55.5%),
      PR 35.5% and failure 4.5%. After CT and RT, CR was 98% (IA-IIA: 100%, IB-IIB:
      95.5%, IIIA: 94.5%). Responses were similar using MOP and MOP/ABVD regimens.
      Fifteen patients relapsed (10%) and 15 died, 11 due to HD and 4 due to other
      causes, while after 7 years overall survival and relapse free survival were
      respectively 87% and 82% (IA-IIA 90% and 85%, IB-IIB: 80% and 80%, IIIA: 87% and
      62%). Results were equivalent irrespective of CT regimen.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1383925
TI  - Structure of the human DNA repair gene HAP1 and its localisation to chromosome
      14q 11.2-12.
AB  - Apurinic/apyrimidinic (AP) sites are pre-mutagenic DNA lesions which occur
      spontaneously and following exposure of cells to ionising radiation or chemical
      mutagens. HAP1 (Human AP endonuclease 1), the major enzyme in human cells
      initiating repair of AP sites, shows strong sequence homology to DNA repair
      enzymes from bacteria, Drosophila and other mammalian species. We have cloned the
      HAP1 gene and determined its complete nucleotide sequence. The site of
      transcription initiation has been mapped to 452 bp upstream of the ATG initiation
      codon in the genomic DNA. The HAP1 gene consists of five exons and is unusually
      small (less than 2.6 kb from transcription initiation site to polyadenylation
      sequence) with 54% of the protein coding region and the entire 3' untranslated
      region contained within a single exon. The first exon is non-coding. Regions of
      three exons show sequence homology to the E.coli xth (exonuclease III) gene.
      Using in situ hybridisation, the HAP1 gene has been localised to human chromosome
      14q 11.2-12.

PMID- 1383926
TI  - Thiolation of transfer RNA in Escherichia coli varies with growth rate.
AB  - We have used an affinity electrophoresis assay which when combined with Northern
      hybridization techniques permits us to estimate the degree of thiolation of
      individual tRNA species in Escherichia coli. We observe that the levels of 4-thio
      2'(3')-uridine (4-thioU) in many but not all tRNAs varies dramatically at
      different bacterial growth rates: Five tRNAs are completely thiolated at all
      growth rates, while another eight tRNAs are incompletely thiolated and the
      fraction of the unthiolated form of these tRNA species increases as the growth
      rates increase. Transfer RNA(2Glu) contains 4-thioU as well as
      (methylamino)methyl-2-thio uridine (mnm(5)2-thioU). The level of mnm(5)2-thioU of
      tRNA(2Glu) is invariant with growth rate. Surprisingly, none of the thirteen tRNA
      species that we have studied is completely unmodified in all growth media. In
      particular, at the slowest growth rates every tRNA class that we have studied
      contains a form that has 4-thioU residues.

PMID- 1383927
TI  - Preparation of 13C and 15N labelled RNAs for heteronuclear multi-dimensional NMR
      studies.
AB  - A procedure is described for the efficient preparation of isotopically enriched
      RNAs of defined sequence. Uniformly labelled nucleotide 5'triphosphates (NTPs)
      were prepared from E.coli grown on 13C and/or 15N isotopically enriched media.
      These procedures routinely yield 180 mumoles of labelled NTPs per gram of 13C
      enriched glucose. The labelled NTPs were then used to synthesize RNA oligomers by
      in vitro transcription. Several 13C and/or 15N labelled RNAs have been
      synthesized for the sequence r(GGCGCUUGCGUC). Under conditions of high salt or
      low salt, this RNA forms either a symmetrical duplex with two U.U base pairs or a
      hairpin containing a CUUG loop respectively. These procedures were used to
      synthesize uniformly labelled RNAs and a RNA labelled only on the G and C
      residues. The ability to generate milligram quantities of isotopically labelled
      RNAs allows application of multi-dimensional heteronuclear magnetic resonance
      experiments that enormously simplify the resonance assignment and solution
      structure determination of RNAs. Examples of several such heteronuclear NMR
      experiments are shown.

PMID- 1383929
TI  - Enhancement of ribozyme catalytic activity by a contiguous oligodeoxynucleotide
      (facilitator) and by 2'-O-methylation.
AB  - RNA catalysts (ribozymes) designed to cleave sequences unique to viral RNA's
      might be developed as therapeutics. For this purpose, they would require high
      catalytic efficiency and resistance to nucleases. Reported here are two
      approaches that can be used in combination to improve these properties. First,
      catalytic efficiency can be improved by oligonucleotides (facilitators) that bind
      to the substrate contiguously with the 3'-end of the ribozyme. Second, 2'-O
      methylation of flanking sequences of the ribozyme increases catalytic activity as
      well as resistance to nucleases. In combination with a facilitator
      oligodeoxynucleotide, the cleavage rate was increased 20 fold over that of the
      unmodified ribozyme.

PMID- 1383930
TI  - Phylogeny and nucleotide sequence of a 23S rRNA gene from Neisseria gonorrhoeae
      and Neisseria meningitidis.

PMID- 1383928
TI  - Preparation of isotopically labeled ribonucleotides for multidimensional NMR
      spectroscopy of RNA.
AB  - A general method for large scale preparation of uniformly isotopically labeled
      ribonucleotides and RNAs is described. Bacteria are grown on isotopic growth
      medium, and their nucleic acids are harvested and degraded to mononucleotides.
      These are enzymatically converted into ribonucleoside triphosphates, which are
      used in transcription reactions in vitro to prepare RNAs for NMR studies. For 15N
      labeling, E.coli is grown on 15N-ammonium sulfate, whereas for 13C-labeling,
      Methylophilus methylotrophus is grown on 13C-methanol, which is more economical
      than 13C-glucose. To demonstrate the feasibility and utility of this method,
      uniformly 13C-labeled ribonucleotides were used to synthesize a 31 nucleotide HIV
      TAR RNA that was analyzed by 3D-NMR. This method should find widespread use in
      the structural analysis of RNA by NMR.

PMID- 1383932
TI  - Quantification of mRNA by non-radioactive RT-PCR and CCD imaging system.

PMID- 1383931
TI  - Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli
      23S ribosomal RNA.
AB  - Interaction of the antibiotics clindamycin and lincomycin with Escherichia coli
      ribosomes has been compared by chemical footprinting. The protection afforded by
      both drugs is limited to the peptidyl transferase loop of 23S rRNA. Under
      conditions of stoichiometric binding at 1 mM drug concentration in vitro, both
      drugs strongly protect 23S rRNA bases A2058 and A2451 from dimethyl sulphate and
      G2505 from kethoxal modification; G2061 is also weakly protected from kethoxal.
      The modification patterns differ in that A2059 is additionally protected by
      clindamycin but not by lincomycin. The affinity of the two drugs for the
      ribosome, estimated by footprinting, is approximately the same, giving Kdiss
      values of 5 microM for lincomycin and 8 microM for clindamycin. The results show
      that in vitro the drugs are equally potent in blocking their ribosomal target
      site. Their inhibitory effects on peptide bond formation could, however, be
      subtly different.

PMID- 1383933
TI  - Rapid mini-preparations of total RNA from bacteria.

PMID- 1383934
TI  - Arbitrarily primed PCR fingerprinting of RNA.
AB  - Fingerprinting of RNA populations was achieved using an arbitrarily selected
      primer at low stringency for first and second strand cDNA synthesis. PCR
      amplification was then used to amplify the products. The method required only a
      few nanograms of total RNA and was unaffected by low levels of genomic double
      stranded DNA contamination. A reproducible pattern of ten to twenty clearly
      visible PCR products was obtained from any one tissue. Differences in PCR
      fingerprints were detected for RNAs from the same tissue isolated from different
      mouse strains and for RNAs from different tissues from the same mouse. The strain
      specific differences revealed are probably due to sequence polymorphisms and
      should be useful for genetic mapping of genes. The tissue-specific differences
      revealed may be useful for studying differential gene expression. Examples of
      tissue-specific differences were cloned. Differential expression was confirmed
      for these products by Northern analysis and DNA sequencing uncovered two new
      tissue-specific messages. The method should be applicable to the detection of
      differences between RNA populations in a wide variety of situations.

PMID- 1383935
TI  - Plasmid cDNA-directed protein synthesis in a coupled eukaryotic in vitro
      transcription-translation system.
AB  - A system is described in which transcription of cDNA clones by bacteriophage T7
      RNA polymerase is coupled to translation in the micrococcal nuclease treated
      rabbit reticulocyte lysate in a single reaction of coupled transcription
      translation. The monovalent and divalent cation requirements for translation are
      dominant for optimum expression in this coupled system, so that transcription is
      relatively inefficient. Nevertheless, the use of appropriate DNA concentrations
      leads to the synthesis of sufficient RNA to saturate the protein synthesis
      capacity of the system. The fidelity and efficiency of expression in this coupled
      system are high, and the degree of purification of the plasmid DNA is relatively
      uncritical. The system therefore offers very considerable advantages for rapid
      screening of 'mini-preparations' of cDNA plasmid constructs for retention of the
      correct reading frame and expression of the desired protein product.

PMID- 1383936
TI  - A comprehensive classification of nucleic acid structural families based on
      strand direction and base pairing.
AB  - We propose a classification of DNA structures formed from 1 to 4 strands, based
      only on relative strand directions, base to strand orientation and base pairing
      geometries. This classification and its associated notation enable all nucleic
      acids to be grouped into structural families and bring to light possible
      structures which have not yet been observed experimentally. It also helps in
      understanding transitions between families and can assist in the design of
      multistrand structures.

PMID- 1383937
TI  - A novel POU family transcription factor is closely related to Brn-3 but has a
      distinct expression pattern in neuronal cells.
AB  - The use of the polymerase chain reaction in conjunction with degenerate
      oligonucleotides has allowed the isolation of cDNA clones derived from each of
      the POU family transcription factors expressed in the proliferating ND7 neuronal
      cell line. In addition to the previously characterized Oct-1, Oct-2 and Brn-3
      factors, ND7 cells have been shown by this means to express a novel POU factor.
      This factor is closely related to Brn-3 but differs at seven amino acids in the
      POU domain, one of which is located in a region which is critical for protein
      protein interactions between different POU proteins. Like Brn-3, the novel factor
      is expressed at high levels in embryonic brain and declines in abundance during
      neuronal development. In contrast to Brn-3 however, it is absent in mature
      sensory neurons and its expression declines during the in vitro differentiation
      of ND7 cells to a non-dividing phenotype whilst Brn-3 expression increases. The
      significance of these distinct but overlapping expression patterns is discussed
      in terms of the possible role of these two factors in regulating neuronal gene
      expression.

PMID- 1383938
TI  - Characterization of the double stranded RNA dependent RNase activity associated
      with recombinant reverse transcriptases.
AB  - An in situ gel assay was applied to the study of double stranded RNA dependent
      RNase activity associated with reverse transcriptase (RT) of HIV-1 and murine
      leukemia virus. Polyacrylamide gels containing [32P] RNA/RNA substrate were used
      for electrophoresis of proteins under denaturing conditions. The proteins were
      renatured and in situ enzymatic degradation of 32P-RNA/RNA was followed. E. coli
      RNaseIII, but not E. coli RNaseH, was active in this in situ gel assay,
      indicating specificity of the assay to RNA/RNA dependent nucleases. Analysis of
      purified preparations of HIV-1 RT p66/p51 expressed in E. coli demonstrated an
      RNA/RNA dependent RNase activity comigrating with the large subunit (p66) of the
      enzyme. In addition, this activity of the RT was often accompanied by a
      contaminating RNA/RNA dependent RNase, with a molecular weight approximately
      30,000 dalton identical to that of E. coli RNaseIII. As the p51 small subunit of
      HIV-1 RT and a mutant of RT p66/p51, at Glutamic acid #478, did not exhibit
      RNA/RNA dependent RNase activity, at least part of the active site of the RNA/RNA
      dependent RNase activity appeared to reside at the carboxy end of the molecule.
      As these RT proteins are also deficient of RNaseH, our results suggest
      overlapping or identical catalytic sites for degradation of the substrates
      RNA/DNA and RNA/RNA.

PMID- 1383940
TI  - Synthesis of backbone deuterium labelled [r(CGCGAAUUCGCG)]2 and HPLC purification
      of synthetic RNA.
AB  - The chemical synthesis of backbone deuterium labelled [r(CGCGAAU*U*CGCG)]2 (U* =
      [5'-2H]U) is described. An efficient purification procedure was developed using a
      polymeric reverse phase (PRP) HPLC column at 60 degrees C. This procedure
      provided pure RNA dodecamer in the multi-milligram quantities (39% overall yield)
      necessary for dynamics studies using solid-state deuterium NMR. The purification
      method has been effectively applied to other RNA sequences and will assist
      biophysical studies which require relatively large quantities of RNA oligomers.

PMID- 1383939
TI  - A comparison of the fidelity of copying 5-methylcytosine and cytosine at a
      defined DNA template site.
AB  - 5-Methylcytosine has been postulated to be an endogenous mutagen in procaryotes
      and eucaryotes leading to base substitution hot spots, C-->T transitions,
      resulting from spontaneous deamination of mC to T. The possibility remains,
      however, that a second mechanism involving mispairing of mC with A might also
      contribute to base substitution mutagenesis via G-->A transitions. Stimulation of
      the G-->A mutational pathway could involve preferential misincorporation of dAMP
      opposite template mC compared to C. To investigate this possibility, we
      synthesized a sequence containing mC at a defined template location. We compared
      the fidelity of copying mC versus C and the efficiency of extending mismatched
      base pairs at the mC position using three DNA polymerases, AMV reverse
      transcriptase, Drosophila DNA polymerase alpha, and mutant Escherichia coli
      Klenow fragment containing no proofreading exonuclease activity. Significant
      differences in misinsertion and mismatch extension efficiencies were observed
      only for the case of AMV reverse transcriptase. AMV reverse transcriptase was
      observed to incorporate dAMP 4 to 5-fold more efficiently opposite mC than C.
      Favored extension of a 5-MeC.A over C.A mispair was also observed with a
      difference of about 3-fold. In contrast to AMV reverse transcriptase, Klenow
      fragment showed no significant difference when copying either mC or C sites or
      when extending mispairs involving mC and C. Incorporation of dAMP opposite either
      C or mC was barely detectable using pol alpha, although pol alpha has been
      observed to form A.C mismatches in other sequences. While we cannot completely
      exclude the possibility that dAMP might be incorporated opposite mC in preference
      to C, our results suggest that contributions of the G-->A pathway to mC mutagenic
      hot spots are likely to be minor, lending additional support to the model
      invoking deamination of mC.

PMID- 1383941
TI  - Chemical synthesis of a biologically active natural tRNA with its minor bases.
AB  - The complete chemical synthesis of an E. coli tRNA(Ala) with its specific minor
      nucleosides, dihydrouridine, ribothymidine and pseudouridine, is reported. The
      method makes use of protected 2'-O-tertiobutyldimethylsilyl-ribonucleoside-3'-O
      (2-cyanoethyl-N- ethyl-N- methyl)phosphoramidites. The exocyclic amino functions
      of the bases were protected by the phenoxyacetyl group for purines and acetyl for
      cytosine. The assembling has been performed on a silica support with coupling
      yield better than 98% within 2 min of condensation. Triethylamine tris
      hydrofluoride allowed a clean and complete deprotection of the tBDMS groups. The
      synthetic tRNA(Ala) has been transcribed into cDNA by reverse transcriptase and
      sequenced. With E. coli alanyl-tRNA synthetase the alanyl acceptance activity and
      kcat/Km were 672 pmol/A260 and 6 x 10(4)M-1s-1, respectively.

PMID- 1383942
TI  - Insertion of non-intron sequence into maize introns interferes with splicing.
AB  - Transposable element (TE) insertion into or near plant introns can cause intron
      skipping and alternative splicing events, resulting in reduced expression. To
      explore the impact of inserted sequences on splicing, we added non-intron
      sequence to two maize introns and tested these chimeric introns in a maize
      transient expression assay. Non-intron sequence inserted into Adh1-S intron 1 and
      actin intron 3 decreased expression from the luciferase reporter gene; the
      insertion sites tested were not in intron regions thought to be essential for
      splicing. Alternatively spliced mRNAs were not observed in transcripts derived
      from the insertion variants. In contrast, addition of an internal segment of an
      intron to Adh1-S intron 1 resulted in normal splice site selection and efficient
      processing. Because the normal intron sequence (including the conserved splice
      junctions) was retained in all constructs, we hypothesize that added non-intron
      sequence can interfere with intron recognition and/or splicing.

PMID- 1383944
TI  - Nucleotide sequences of the cDNA encoding wheat elongation factor 1 beta'.

PMID- 1383943
TI  - A novel murine homeobox gene isolated by a tissue specific PCR cloning strategy.
AB  - We have identified a novel homeobox gene, designated K-2, using a reverse
      transcription PCR cloning strategy. Sequence analysis reveals that the homeobox
      of K-2 is 77.6% homologous at the nucleotide level and 97% identical at the amino
      acid sequence level to another murine gene, S8. Homeodomain sequence comparisons
      indicate that K-2 and S8 represent a distinct subclass of paired type homeobox
      genes. Northern blot analysis of RNA from murine embryos and adult tissues
      identified multiple transcripts that are expressed in a developmentally specific
      and tissue restricted manner. Alternate splicing of K-2 at the 3-coding region
      leads to the inclusion of a chain terminating sequence. In addition, the
      developmental expression pattern of this gene at day 12 of gestation was
      determined by in situ hybridization. Expression was observed in diverse
      mesenchymal cells in craniofacial, pericardial, primitive dermal, prevertebral,
      and genital structures.

PMID- 1383945
TI  - Conserved residues and secondary structure found in small cytoplasmic RNAs from
      thirteen Bacillus species.

PMID- 1383946
TI  - PRE: a novel element with the hallmarks of a retrotransposon derived from an
      unknown structural RNA.

PMID- 1383947
TI  - Effects of group interventions on cognition and depression in nursing home
      residents.
AB  - The effects of cognitive-behavioral group therapy, focused visual imagery group
      therapy, and education-discussion groups on cognition, depression, hopelessness,
      and dissatisfaction with life were studied among depressed nursing home
      residents. Seventy-six depressed subjects with mild to moderate cognitive decline
      participated in nurse-led 24-week protocols. Data were collected 4 weeks before
      the interventions, 8 and 20 weeks after treatment initiation, and 4 weeks after
      treatment termination. There were no significant changes in depression,
      hopelessness, or life satisfaction scores for any of the three conditions.
      Participants in the cognitive-behavioral and focused visual imagery groups showed
      a significant improvement beginning 8 weeks after treatment initiation on
      cognitive scores. These findings are encouraging indications that cognitive
      behavioral and focused visual imagery group therapies may reduce cognitive
      impairment in depressed nursing home residents with mild to moderate cognitive
      decline.

PMID- 1383948
TI  - Paediatric day surgery.
AB  - An in-depth study of the experience of 10 children admitted for day surgery
      revealed that parents received little information before the admission and that
      this was not compensated for by the information given on admission. Most of the
      children underwent excessively long pre-operative fasts and only three out of the
      10 children were actually discharged on the day of their operation.

PMID- 1383949
TI  - In search of a perfect partnership.
AB  - There's no question that our partnership is a natural, given the technological
      emphasis in modern medicine. My comments are not intended as criticism, but
      offered in the spirit of broadening our mutual understanding. I believe that open
      communication will enhance our continued collaboration in this interdisciplinary
      effort and yield significant advances in medical science.

PMID- 1383950
TI  - Assessment of long-term stability of chronic ventricular pacing thresholds in
      steroid-eluting electrodes.
AB  - Sixteen patients with Medtronic 4003 steroid-eluting electrodes implanted in the
      ventricular position were followed over 5 years. In each patient a special type
      of Medtronic 2443 pacemaker was implanted to allow programming of output at 1.35
      V. Chronic threshold values in these patients measured at an output of 1.35 V
      were stable over the first 18 months of follow-up. Mean values were: 0.06 +/-
      0.03 msec at 6 months and 0.08 +/- 0.02 msec at 18 months; these did not differ
      from each other significantly. However, during the period from 18 to 36 months
      postimplantation, a significant increase in mean pacing threshold was observed:
      0.08 +/- 0.02 msec at 18 months postimplantation versus 0.14 +/- 0.05 msec at 36
      months (P < 0.01). After 36 months, the chronic pacing threshold remained stable
      until the end of the 5-year follow-up period. Further long-term study of chronic
      threshold behavior of steroid-eluting electrodes measured at low amplitudes is
      warranted.

PMID- 1383951
TI  - Exercise induced fatal sinusoidal ventricular tachycardia secondary to
      moricizine.
AB  - Moricizine has been touted as having a low incidence of proarrhythmic effects. We
      present a case of proarrhythmia from moricizine, which presented as exercise
      induced ventricular tachycardia, and review the literature suggesting that this
      antiarrhythmic drug shares the proarrhythmic profile of other agents with
      predominant type Ic action. We conclude that moricizine has certain clinical and
      electrophysiological features that resemble type Ic antiarrhythmic agents.
      Precautions similar to those used when prescribing other drugs of this type
      should be followed when prescribing moricizine, including predischarge exercise
      testing.

PMID- 1383952
TI  - VDD pacing with a previously implanted single lead system.
AB  - Three patients who had undergone implantation of a rate modulated, atrial
      sensitive RS4 pacemaker, with a single orthogonal lead underwent replacement of a
      depleted unit with a DDD pulse generator, reusing the original lead with an
      adapter that allowed conversion of the bipolar atrial electrode into unipolar
      configuration. The mean atrial electrogram amplitude was 1.8 mV and no
      significant atrial sensing defects were found during Holter monitoring. As the
      RS4 pulse generator is no longer available, continued VDD pacing is possible by
      replacing it with a DDD pulse generator using the previously implanted single
      lead system.

PMID- 1383954
TI  - Acute and chronic cycle length dependent increase in ventricular pacing
      threshold.
AB  - Several factors have been shown to influence ventricular pacing threshold in
      humans, including pacing lead location (endocardial vs epicardial), lead
      maturation, and antiarrhythmic agents. To determine whether ventricular pacing
      rate has a significant influence on acute and chronic pacing thresholds, we
      measured pacing thresholds in 16 patients receiving an implantable
      antitachycardia pacemaker cardioverter defibrillator (Cadence). Ventricular
      pacing thresholds were determined using the device programmer at cycle lengths of
      600, 400 and 300 msec at the time of implantation; prior to hospital discharge at
      3-14 days; and during follow-up outpatient visits at 6-8 weeks, 3 months, and 6
      months to 1 year. Eleven patients had an epicardial lead system and five an
      endocardial lead system. Eleven patients were being treated with antiarrhythmic
      drug therapy. Device output ranged from 1-10 V and was adjustable in 1-V
      increments (pulse width was held constant at 1 msec). A cycle length dependent
      increase in pacing threshold (defined as a > or = 1-V increase in threshold at
      400 or 300 msec relative to 600 msec) was observed in 10/16 patients during 12/72
      pacing trials at 400 msec, and in 15/16 patients during 31/67 trials at 300 msec.
      In trials in which an increase in pacing threshold occurred, the magnitude of the
      increase at 400 msec relative to 600 msec was only 1 V in all 12 trials, but at
      300 msec the increase ranged from 4-9 V in 7/31 (23%) trials.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1383953
TI  - The importance of muscle relaxation in dynamic cardiomyoplasty.
AB  - During the last decade dynamic cardiomyoplasty has been introduced as a new
      method to treat patients with severe heart failure. This procedure consists of
      the wrapping of the latissimus dorsi (LD) muscle around the heart with electrical
      stimulation of the muscle synchronous to cardiac contraction. The optimal pacing
      mode of the muscle, during the conditioning and working period of the LD muscle,
      is still unclear. The pace protocol, currently used worldwide, has a maximal
      number of muscle tetanic contractions of 100 per minute. Data are presented on
      the LD muscle contraction characteristics using that protocol. Both force
      measurements from six in situ stimulated goat LD muscles and x-ray evaluation of
      the movement of metallic clips on wrapped LD muscles in two patients were used.
      Results demonstrate that LD muscle force is well maintained at the maximal rate
      of 100 contractions per minute but relaxation is severely hampered. This may lead
      to diminished support of the failing heart and damage of the wrapped muscle. A
      pacing protocol is proposed using a lower maximal stimulation rate.

PMID- 1383955
TI  - The effects of type I antiarrhythmic drugs on the signal-averaged
      electrocardiogram in patients with malignant ventricular arrhythmias.
AB  - The effects of type I antiarrhythmic drugs on the signal-averaged
      electrocardiogram (SAECG) were analyzed in 58 patients with inducible sustained
      monomorphic ventricular tachycardia. SAECGs were acquired before and after drug
      therapy. A total of 99 drug trials were analyzed (mean 1.7 per patient). Analysis
      of temporal domain parameters included the duration of the QRS complex (QRSD),
      the high frequency total duration of the filtered QRS complex (HFTD), the
      duration of the signal under 40 microV (D40), initial QRS (HFTD minus D40), and
      the root mean square amplitude (RMSA) of the terminal 40 msec of the QRS signal.
      Changes in temporal parameters failed to predict drug efficacy. There were,
      however, type-specific drug effects on the SAECG. With the exception of type IB
      drugs, all drugs increased the QRSD, HFTD, and D40. Type IC drugs caused more
      prolongation of the QRSD and HFTD than type IA, IB, and the combination of IA+IB
      drugs. Prolongation of the HFTD was related to prolongation of the late potential
      and the initial portion of the QRS complex. A preferential effect of these drugs
      on the late potential was not observed. Type IC drugs also caused more
      prolongation of ventricular tachycardia cycle length than type IA or IB drugs.
      However, the increase in ventricular tachycardia cycle length did not correlate
      with a change in the SAECG. In summary, type I antiarrhythmic drugs cause a
      global slowing of ventricular activation. Although analysis of the SAECG
      following drug therapy was not useful for predicting drug efficacy, drug induced
      changes in the SAECG may be helpful for categorizing antiarrhythmic agents.

PMID- 1383956
TI  - Right-sided versus left-sided radiofrequency ablation of the His bundle.
AB  - Radiofrequency (RF) ablation of the His bundle was attempted in 30 consecutive
      patients with atrial flutter or fibrillation. A 7 French quadripolar catheter
      with a 4-mm distal electrode was advanced from the right femoral vein (21
      patients), or subclavian vein (two patients) and positioned across the tricuspid
      valve. Adequate His-bundle potentials were obtained in all patients. However, in
      six patients atrioventricular (AV) block could not be obtained after multiple
      (mean = 8) applications of RF energy from the conventional right-sided approach.
      In these patients the same catheter was advanced to record a His potential
      through a retrograde arterial approach. AV block was created in all patients with
      one to three applications of RF energy. The duration of the procedure was 22 to
      90 minutes for the right-sided approach and 5 to 10 for the left-sided approach
      (P < 0.005). Subsequently, in seven patients a left-sided approach was used
      first. One to six applications of RF energy were required to create AV block. The
      radiation exposure time was 3 to 20 minutes. No complications occurred.
      CONCLUSIONS: RF ablation of the His bundle seems easier using a left-sided than a
      right-sided approach, reduces procedure and radiation time, and avoids recovery
      of conduction. These data suggest that a left-sided approach, in spite of
      requiring arterial catheterization, may be preferable to a right-sided approach.

PMID- 1383957
TI  - Successful radiofrequency current catheter ablation of sustained ventricular
      tachycardia.
AB  - We performed radiofrequency current catheter ablation in two patients with
      nonischemic sustained ventricular tachycardia (VT). In one patient, two
      morphologically distinct VTs were induced by electrical stimulation. One showed
      right bundle branch block pattern and the other left bundle branch block pattern.
      The earliest site of activation during each VT was determined at the septum of
      the right ventricle. However, these two sites were close to the His-bundle
      electrogram recording area. In the other patient, a VT with a left bundle branch
      block pattern occurred spontaneously after the administration of isoproterenol.
      The earliest site of activation during VT was determined at the outflow tract of
      the right ventricle. During tachycardia, radiofrequency current ablation (40 W x
      30 sec) was delivered to the earliest site of activation. A few seconds after
      fulguration, each VT was terminated and additional radiofrequency currents were
      given near these sites. After the ablation, VT could not be induced by the
      electrical stimulations, nor did it recur. No side effects were observed and the
      atrioventricular conduction remained intact. We feel that nonischemic VTs could
      possibly be treated by using radiofrequency current catheter ablation.

PMID- 1383958
TI  - Quality-of-life in patients treated with atrioventricular synchronous pacing
      compared to rate modulated ventricular pacing: a long-term, double-blind,
      crossover study.
AB  - To investigate whether the preservation of atrioventricular (AV) synchronization
      matters for quality-of-life during pacemaker treatment we assessed 17 consecutive
      patients with high degree AV block and preserved sinus node function in a double
      blind, long-term crossover study. A questionnaire with regard to cardiovascular
      symptoms, sleep disturbances, cognitive functioning, physical ability, social
      interaction, emotional functioning, and self-perceived health was completed after
      2 months of atrial synchronous (DDD) and rate modulated ventricular pacing
      (VVI,R), respectively. A significant improvement in shortness of breath,
      dizziness and palpitations as well as an improvement of cognitive functioning was
      observed during DDD pacing. Nine patients preferred the DDD mode and three the
      VVI,R mode. The remaining five patients did not express any preference. The
      preference for the DDD mode was explained by a significant reduction of
      cardiovascular symptoms and an improved self-perceived health, physical ability,
      and psychological well-being during DDD pacing. All differences in quality-of
      life parameters between the two modes of pacing favored the DDD mode and no
      adverse effects of this mode were found. Thus, the maintenance of AV synchrony
      adds further symptomatic relief compared to rate increase alone. The results
      indicate that DDD pacing is the preferred mode of pacing in patients with high
      degree AV block and preserved sinus node function.

PMID- 1383960
TI  - Effects of chronotropic responsive cardiac pacing on ventilatory response to
      exercise in patients with complete AV block.
AB  - To identify the effect of chronotropic responsive cardiac pacing on the
      ventilatory response to exercise, ten selected patients with complete
      atrioventricular block underwent paired cardiopulmonary exercise tests in fixed
      rate ventricular (VVI) and dual chamber (DDD) or rate responsive ventricular
      (VVIR) pacing modes. Compared to VVI pacing, DDD or VVIR pacing increased peak
      oxygen uptake (P < 0.005) and augmented anaerobic threshold (P < 0.001). In eight
      patients, dyspnea was the major symptom limiting exercise with VVI pacing and
      this was markedly attenuated with DDD or VVIR pacing. In all patients,
      ventilation (VE) and the ratio of ventilation to CO2 production (VE/VCO2) were
      consistently higher with VVI pacing during exercise. To compare the response of
      the two pacing modes at the same workloads in an aerobic condition, we measured
      ventilatory variables 1 minute prior to the anaerobic threshold obtained with VVI
      pacing. When DDD or VVIR pacing was compared with VVI pacing, VE and VE/VCO2
      significantly decreased from 20.5 +/- 5.3 L/min to 18.3 +/- 5.0 L/min (P < 0.005)
      and from 35.9 +/- 5.8 to 31.9 +/- 5.0 (P < 0.001), respectively. Respiratory
      frequency rose significantly more with VVI pacing (P < 0.001) despite an
      unchanged tidal volume. Although peak VE did not differ between the two pacing
      modes, VE/VCO2 at the peak exercise increased significantly more with VVI pacing
      (P < 0.005). Respiratory frequency also rose more with VVI pacing (P < 0.005) and
      tidal volume did not change. This study suggests that chronotropic responsive
      cardiac pacing attenuates the exertional dyspnea by improving the ventilatory
      response to exercise as well as increasing the cardiac output in patients with
      complete atrioventricular block.

PMID- 1383959
TI  - Reproducibility of head upright tilt table test results in patients with syncope.
AB  - Head upright tilt table testing is a promising technique for the evaluation and
      management of vasovagal (neuroregulatory) syncope. In order to determine the day
      to-day reproducibility of results using this technique we performed head upright
      tilt table testing (with or without graded isoproterenol infusion) in 21 patients
      (12 males, 9 females, mean age 34 +/- 19.1 years). During the first tilt study a
      total of 14 patients experienced syncope (six during baseline tilt, mean tilt
      time 15.8 +/- 7 minutes, eight following tilt with graded isoproterenol infusion,
      mean tilt time 17.7 +/- 9 minutes) while seven were negative. During the second
      tilt study (performed 3-7 days following the first study) the results of the
      first study were duplicated in 19 patients (90%) (six during baseline tilt, mean
      time 17.5 +/- 8 minutes, eight following graded isoproterenol infusion, mean time
      15.9 +/- 7 minutes), however the level of provocation required to provoke syncope
      differed from that needed in the initial test in five patients (24%). We conclude
      that the results of head upright tilt table testing with graded isoproterenol
      infusions can be duplicated in 90% of patients, although some day-to-day
      variability exists in the degree of provocation necessary to elicit a positive
      response.

PMID- 1383961
TI  - The effects of selective stellate ganglion manipulation on ventricular
      refractoriness and excitability.
AB  - The effects of selective stellate ganglion stimulation or stellectomy on
      ventricular excitability were studied in 30 open chest mongrel dogs anesthetized
      with alpha-chloralose. The effective refractory period (ERP) and strength
      interval curves (stimulus intensity [S2] = twice the diastolic threshold [ERP],
      and 2, 3, 5, 7, and 14 mA) were determined using bipolar epicardial electrodes
      placed in the mid-anterior wall of the right ventricle (RV) and the mid
      posterolateral wall of the left ventricle (LV) during left stellate ganglion
      stimulation (LSGSt, n = 8) or right stellate ganglion stimulation (RSGSt, n = 8),
      or after left stellectomy (LSGEx, n = 7) or right stellectomy (RSGEx, n = 7).
      LSGEx prolonged ERP-LV (172 +/- 9 vs 167 +/- 8 msec, P < 0.05) and ERP-RV (163 +/
      10 vs 158 +/- 14 msec, P < 0.05). RSGEx prolonged ERP-LV (168 +/- 17 vs 162 +/-
      15 msec, P < 0.01) and ERP-RV (166 +/- 14 vs 160 +/- 13 msec, P < 0.01), and the
      times of the strength interval curves obtained for each S2 intensity in both
      ventricles. LSGSt decreased ERP-LV (157 +/- 11 vs 163 +/- 12 msec, P < 0.01) and
      ERP-RV (147 +/- 18 vs 157 +/- 17 msec, P < 0.05), and the times of the strength
      interval curves obtained for each S2 intensity in both ventricles. RSGSt did not
      significantly decreased ERP-LV (152 +/- 11 vs 156 +/- 9 msec); however, it
      significantly shortened the times of the strength interval curves obtained for S2
      intensities of 2 and 7 mA in the LV, and shortened ERP-RV (139 +/- 10 vs 145 +/-
      7 msec, P < 0.01) and the times of the strength interval curve for S2 intensities
      of 2, 3, and 5 mA in the RV. A significant interaction (MANOVA test) was observed
      between the ventricle studied and the ganglion stimulated for S2 intensities of 2
      and 3 mA, and between the effect of stimulation and the ganglion stimulated for
      S2 intensities of 3 and 14 mA. To conclude, selective stellectomy prolonged
      epicardial ventricular refractoriness in both the mid-anterior wall of the RV and
      the mid-posterolateral wall of the LV; the magnitude of the epicardial
      excitability variations in both areas was different during selective stellate
      ganglion stimulation.

PMID- 1383963
TI  - Evaluation of transesophageal atrial pacing stethoscope in adult surgical
      patients under general anesthesia.
AB  - Sinus bradycardia (SB) and atrioventricular junctional rhythm (AVJR) commonly
      cause circulatory insufficiency in anesthetized surgical patients. Treatment is
      usually with drugs, which can be ineffective or have adverse effects. Cardiac
      pacing might be preferred, but the transvenous or epicardial routes are too
      invasive for routine use, and transcutaneous pacing fails to preserve atrial
      transport function. Transesophageal atrial pacing (TAP) lacks these
      disadvantages, yet unavailability of inexpensive products has prevented more
      widespread use. Therefore, a pacing esophageal stethoscope (PES) fabricated by
      addition of bipolar electrodes to disposable esophageal stethoscopes routinely
      used for intraoperative monitoring, was evaluated in 100 anesthetized adults. TAP
      thresholds (10-msec pulses) and hemodynamic effects of TAP as treatment for
      incidental SB (< or = 60 beats/min) or AVJR were determined. Minimum TAP
      thresholds (mean +/- standard error) in 48 males were 7.3 +/- 0.3 mA and in 51
      females were 8.5 +/- 0.4 mA. Corresponding inferior alveolar ridge-to-electrode
      distances were 32.5 +/- 0.2 and 30.4 +/- 0.2 cm. For 48 patients with SB < or =
      60 beats/min (54 +/- 1 beats/min), TAP (81 +/- 1 ppm) produced average 15, 11,
      and 14 mmHg increases in systolic, diastolic, and mean arterial pressure,
      respectively (P < 0.001). For 11 patients with AVJR (71 +/- 5 beats/min), TAP (92
      +/- 3 ppm) produced average 23 and 15 mmHg increases in systolic and mean
      arterial pressure, respectively (P < 0.05). There were no apparent complications
      of TAP. TAP with a PES appears practical, safe, and effective for prophylaxis and
      treatment of SB or AVJR in anesthetized surgical patients.

PMID- 1383962
TI  - Atrial arrhythmia management with sensor controlled atrial refractory period and
      automatic mode switching in patients with minute ventilation sensing dual chamber
      rate adaptive pacemakers.
AB  - Although a long postventricular atrial refractory period (PVARP) may prevent the
      occurrence of pacemaker mediated tachycardias and inadvertent tracking of atrial
      arrhythmias in dual chamber (DDD) pacing, the maximum upper rate will necessarily
      be compromised. We tested the feasibility of using minute ventilation sensing in
      a dual chamber rate adaptive pacemaker (DDDR) to shorten the PVARP during
      exercise in 13 patients with bradycardias (resting PVARP = 463 +/- 29 msec) to
      avoid premature upper rate behavior. Graded treadmill exercise tests in the DDD
      and DDDR modes at this PVARP resulted in maximum ventricular rates of 98 +/- 8
      and 142 +/- 3 beats/min, respectively (P < 0.0001), due to chronotropic
      incompetence and upper rate limitation in the DDD mode, both circumvened with the
      use of sensor. In order to stimulate atrial arrhythmias, chest wall stimulation
      was applied for 30 seconds at a rate of 250 beats/min at a mean unipolar atrial
      sensitivity of 0.82 mV. Irregular ventricular responses occurred in the DDD mode
      (the rates at a PVARP of 280 and 463 +/- 29 msec were, respectively 92 +/- 5 and
      66 +/- 3 msec; P < 0.0001). In the DDDR mode at a PVARP of 463 +/- 29 msec,
      regular ventricular pacing at 53 +/- 2 beats/min occurred due to mode switching
      to VVIR mode in the presence of repetitive sensed atrial events within the PVARP.
      One patient developed spontaneous atrial fibrillation on follow-up, which was
      correctly identified by the pacemaker algorithm, resulting in mode switch from
      DDDR to regular VVIR pacing and preservation of rate response. In conclusion,
      sensor controlled PVARP allows a long PVARP to be used at rest without limiting
      the maximum rate during exercise. In addition, to offer protection against
      retrograde conduction, a long PVARP and mode switching also limit the rate during
      atrial arrhythmias and allow regular ventricular rate responses according to the
      physiological demands.

PMID- 1383964
TI  - Prophylactic pacing for prevention of sudden death in congenital complete heart
      block?

PMID- 1383965
TI  - Comparison of subxiphoid and traditional approaches for ICD implantation.
AB  - We compared clinical and electrophysiological data in 18 patients undergoing ICD
      implantation via a traditional (median sternotomy or left lateral thoracotomy)
      with 29 patients with a subxiphoid approach. Both groups were similar in terms of
      age, sex, left ventricular ejection fraction, presence of coronary artery
      disease, and clinical indication for the device. Fifteen patients (83%) with the
      traditional approach had previous cardiac surgery compared with 6 patients (21%)
      who had a subxiphoid approach (P < 0.001). Both groups had similar patch R wave
      and sensing R wave measurements. Patients with the traditional approach had a
      lower energy for defibrillation than patients with a subxiphoid approach (13.6 +/
      6.8 J vs 17.9 +/- 4.1 J, P < 0.05). Postoperative hospital days were fewer in
      the subxiphoid group compared with the traditional approaches (9.8 +/- 5.3 vs
      13.7 +/- 7.5 days) but the differences did not reach statistical significance,
      possibly due to small numbers. The subxiphoid approach appears to be a reasonable
      alternative approach to the traditional approach in selected patients undergoing
      ICD implantation.

PMID- 1383966
TI  - Operating systems.

PMID- 1383967
TI  - Exercise tests with different modifications to evaluate rate adaptive pacemakers.

PMID- 1383968
TI  - Performance of implantable cardiac rhythm management devices.

PMID- 1383969
TI  - Clinical experience with a helical bipolar stimulating lead.
AB  - Over 100 patients have been treated for partial epilepsy using a NeuroCybernetic
      Prosthesis System (NCP). The NCP System is comprised of an implantable pulse
      generator, an implantable bipolar stimulating lead, and an external communication
      system. The lead delivers electrical impulses from the NCP Generator to the vagus
      nerve, and includes a connector end that plugs into the generator, a silicone
      insulated lead body, and the helical electrode array that attaches to the nerve.
      The surgical implantation technique has a significant impact on lead reliability
      and performance. The lead electrode has performed well to date. Modifications to
      further improve reliability have been implemented. Clinical experience, case
      history examples, and voltage measurements are examined. The lead electrode is an
      important component of the overall system and plays a significant part in the
      success of vagus nerve stimulation therapy.

PMID- 1383970
TI  - Treatment of refractory partial seizures: preliminary results of a controlled
      study.
AB  - Vagus nerve stimulation for the treatment of epilepsy has been studied in
      medically refractory patients with partial seizures in a randomized, blinded,
      parallel study. After a 3-month baseline period, the patients were implanted with
      the Neurocybernetic Prosthesis (NCP) system consisting of the NCP Generator and
      the Bipolar Vagal Stimulation Lead. Two stimulation paradigms were used, HIGH,
      which delivers what is considered to be optimal stimulation parameters and LOW,
      which is considered to be less or noneffective. The system and vagus nerve
      stimulation were well tolerated and few adverse events have been attributed to
      either. One patient experienced a period of direct current to the nerve due to a
      generator malfunction. This results in paralysis of the left vocal cord. Efficacy
      analysis on the first 37 patients to complete the controlled portion of the study
      has shown that the patients in the HIGH group experienced a mean reduction in
      seizure frequency of 33.3% and patients in the LOW group experienced a mean
      reduction in seizure frequency of 8.4%. The difference between the groups is
      statistically significant with a P value of 0.025. Analysis of seizure duration
      and intensity does not show any significant change. Ratings of the patient's
      overall condition by the patient, investigator, and companion as a measurement of
      "quality of life" also show improvement in the HIGH group. The results of this
      interim study demonstrate that vagus nerve stimulation is a safe and effective
      method of treating partial epileptic seizures.

PMID- 1383971
TI  - Chronic vagus nerve stimulation increases the latency of the thalamocortical
      somatosensory evoked potential.
AB  - The Neurocybernetic Prosthesis (NCP) is a pacemaker-like device that has been
      designed to provide chronic intermittent vagus nerve stimulation. It is currently
      under study for the treatment of refractory partial onset epilepsy, and
      preliminary studies have indicated that partial onset seizures are improved by
      this therapy. The mechanisms by which it exerts its antiepileptic effect are not
      well understood. Although there are extensive pathways to the forebrain from the
      nuclei of the vagus nerve, the evidence that the NCP alters neural transmission
      outside the vagal system is limited. We prospectively examined somatosensory and
      brain stem auditory evoked potentials (BAEPs) in three patients receiving NCP
      implantation to determine if changes in these studies occur as a result of
      chronic vagus nerve stimulation. The results demonstrate a significant
      prolongation of the cervicomedullary to thalamocortical potential (N13-N20)
      interval on somatosensory evoked potential (SSEP) studies following activation of
      the device. No other significant changes were seen on SSEP or BAEP in the NCP
      implanted patients or normal controls. The findings suggest that chronic vagus
      nerve stimulation does alter neuronal networks outside of the brain stem vagus
      system, and may potentially provide a means to clinically monitor and titrate
      this therapy.

PMID- 1383972
TI  - Regional cerebral blood flow in man manipulated by direct vagal stimulation.

PMID- 1383973
TI  - Neurocardiac responses to vagoafferent electrostimulation in humans.
AB  - To determine if cardiac vagal tone is enhanced by vagal electrostimulation (VES),
      we examined the heart rate autospectrum (HRA) in eight patients with implanted
      stimulators for complex partial seizures. In four patients the VES was activated
      at 30 Hz and 500-msec pulse (HiStim group) compared to 2 Hz and 130-msec pulse
      for the LoStim group (n = 4). Continuous ECG and respiratory waveforms were
      recorded for 45 minutes every 8 hours (7-8 AM; 3-4 PM 11-12 PM) during resting
      supine wakeful epochs both before and 15 days after surgical implantation. From
      the HRA cardiac sympathovagal balance was expressed as the ratio of the low
      frequency (LF) power to the high frequency (HF) power. RESULTS: There were no
      presurgical differences between the groups in heart rate, its variance, or the
      energies contained in any autospectral band. The LoStim group showed no
      significant change in heart rate (HR), HF peak power, or LF:HF ratios during 2
      weeks of VES. Conversely, in the HiStim group, the LF:HF peak power ratio (an
      expression of sympathetic dominance) decreased from 2.5 +/- 1.5 preimplant to 1.5
      +/- 0.49 (P < 0.02) with VES. During VES there was a significantly higher HF
      power in the HiStim compared to LoStim group. No diurnal variations in HRA values
      were seen for either group. CONCLUSIONS: (1) A relationship exists between
      selective vagal nerve electrostimulation and the HRA; and (2) high stimulation
      frequency of the vagus nerve in man is associated with sustained augmentation of
      cardiac vagal tone throughout a 24-hour cycle.

PMID- 1383974
TI  - Effects of chronic left vagal stimulation on visceral vagal function in man.
AB  - We examined the effects of chronic left vagal electrostimulation on afferent and
      efferent gastrointestinal vagal function in eight patients. Afferent function was
      assessed using cortical evoked responses to electrical stimulation of the
      esophagus and to direct vagal stimulation using the implanted left vagal
      electrode. Efferent gastrointestinal vagal function was measured by examining the
      basal, maximal, and sham fed stimulated gastric acid output prior to and with
      chronic left vagal electrostimulation. Esophageal electrostimulation produced a
      cortical evoked response consisting of three negative and three positive peaks
      within 400 msec after stimulation. Prior to vagal electrostimulation the mean
      conduction velocity of the afferent signal was measured at 8.72 +/- 3.39 m/sec,
      compatible with A-delta fibers involvement. Basal, maximal, and sham fed acid
      output were 1.11, 21.87, and 9.37 mmol/hour, respectively. The evoked response to
      esophageal electrical stimulation was not changed with chronic left vagal
      electrostimulation. Direct vagal stimulation also produced evoked potentials that
      were comparable to those obtained with esophageal stimulation. The mean
      conduction velocity was 6.26 +/- 2.72 m/sec (NS) so that there was no evidence of
      loss of myelinated fibers with chronic stimulation. No differences were detected
      in basal (1.29 mmol/h), maximal (21.64 mmol/h), or sham fed stimulated (8.03
      mmol/h) acid output, showing that vagal electrostimulation has no effect on
      either total or vagally mediated acid output, an efferent vagal function. In
      conclusion, chronic left vagal electrostimulation has no significant adverse
      effect on gastrointestinal vagal function.

PMID- 1383975
TI  - Evidence of impaired afferent vagal function in patients with diabetes
      gastroparesis.
AB  - Two patients, a 28-year-old male and a 70-year-old female, with chronic insulin
      dependent diabetes mellitus and evidence of autonomic neuropathy were studied
      using cortical evoked responses following esophageal balloon and electrical
      stimulation. Both patients had symptomatic gastroparesis, poor gastric emptying,
      and reduced gastroduodenal motility including abnormal results of scintigraphy
      and manometry. There was slowing of afferent vagal conduction but good evoked
      potential responses were recorded even though one patient could not feel
      electrical stimulation of either the proximal or distal esophagus. It is
      improbable that the gastric symptoms are due to an afferent autonomic neuropathy,
      but symptoms may well be related to impairment of motor vagal pathways.
      Nevertheless, afferent vagal pathways are involved in severe diabetes mellitus.
      The clinical significance of this delay in conduction velocity of afferent
      pathways remains to be established.

PMID- 1383976
TI  - Cognitive motor function after electrical stimulation of the vagus nerve.
AB  - Chronic stimulation of the vagus nerve does not seem to produce significant
      differences between high frequency and low frequency stimulation groups.
      Individuals within each group show significant changes between preoperative
      assessment and after 6-month stimulation. Some subjects showed significant
      improvement and some showed significant slowing of responses. Subjects who showed
      improvement are still considerably slower than normals, but all patients have a
      very long history of complex partial seizures and exposure to multiple
      medications. Larger homogeneous sample sizes are needed to delineate more clearly
      the correlation between cognitive performance, medication effects, and
      stimulation effects.

PMID- 1383977
TI  - Acute effects of high frequency vagal nerve stimulation on balance and cognitive
      motor performance in epilepsy: three case study reports.
AB  - Quantitative measures of area of sway, total sway, and cognitive function failed
      to show significant differences in acute (50 minute) "ON-OFF-ON-OFF" studies of
      high frequency left vagal stimulation in three epileptic patients undergoing
      treatment for chronic complex partial seizures. Fluctuation in blood levels of
      anticonvulsants may have been associated with some clinical effects. There were
      no significant adverse effects of acute left vagal stimulation in these three
      subjects.

PMID- 1383978
TI  - Electrostimulation effects of the vagus nerve on balance in epilepsy.
AB  - Preliminary results of selected postural measures in quiet standing indicate that
      stimulation of the vagus nerve appears not to be producing adverse effects. With
      this specific sample size, more testing is needed to determine long-term effects
      and future data analyses will examine correlations between electroencephalogram
      results, drug levels, and seizure frequency. In the present study three subjects
      have had old injuries to hips and ankles. Two subjects had normal values for
      postural control prior to stimulation, while other subjects were severely
      abnormal. In future, studies should include larger homogeneous sample sizes, as
      the current subjects show marked variability in age and premorbid health
      backgrounds. Future work should also control more vigorously for variables such
      as visual input (i.e., blindfolding subjects instead of simply closing the eyes).
      Evaluation of postural control mechanisms will be continued to assess stability
      changes in these patients as seizure frequency continues to subside.

PMID- 1383979
TI  - Catheter ablation: a "former" arrhythmia surgeon's view.

PMID- 1383980
TI  - Hemothorax associated with anticoagulation after placement of implantable
      cardioverter defibrillator: possible similarity to postinfarction Dressler's
      syndrome.
AB  - Massive hemothorax developed after placement of an implantable cardioverter
      defibrillator (ICD) in two patients who received postoperative anticoagulants.
      The possible relationship of this complication to polyserositis after ICD
      implantation is discussed as are the possible adverse sequelae of early
      anticoagulation after ICD implantation.

PMID- 1383981
TI  - Ventricular lead transection and atrial lead damage in a young softball player
      shortly after the insertion of a permanent pacemaker.
AB  - We report a case in which permanent pacemaker implantation using a conventional
      subclavian approach on the throwing side of an avid softball player resulted in
      complete transection of the ventricular lead and severe damage to the atrial
      lead. The site of the lead fracture suggested that both leads were crushed
      between the clavicle and the first rib as a result of the frequent and repetitive
      arm movement. This case illustrates the importance of the selection of the
      correct approach for permanent pacing lead insertion.

PMID- 1383982
TI  - Proarrhythmia in patients treated with moricizine.

PMID- 1383983
TI  - A technique utilizing a steerable hydrophilic guidewire for permanent pacemaker
      implantation.
AB  - We report the use of a steerable hydrophilic guidewire for permanent pacemaker
      implantation. This wire, previously used for peripheral vascular and cardiac
      angiography, is able to be steered and passed in many situations when a standard
      guidewire cannot be used. We report three cases where the standard J-tipped
      guidewire could not be passed by either the cephalic or subclavian route and the
      hydrophilic guidewire allowed for successful atraumatic placement of a sheath and
      pacemaker lead.

PMID- 1383984
TI  - Supernormal conduction in the left bundle branch unmasked by the linking
      phenomenon.
AB  - This presentation reflects a case of phase-3 left bundle branch block (LBBB).
      Analysis reveals that relatively early QRS complexes are wide, whereas beats
      occurring later than a critical time are narrow. There are, however, two
      unexpected phenomena: (1) an overlap occurs between the range of R-R intervals
      resulting in normal intraventricular conduction and the range of R-R intervals
      resulting in LBBB pattern. Complexes that follow a wide beat are often wide
      although they are associated with relatively long R-R intervals, whereas
      complexes that follow a normal beat tend to be normal even after relatively short
      R-R cycles. This is due to concealed retrograde penetration of the bundle branch
      that is blocked in anterograde direction (the so-called linking phenomenon). (2)
      Some early supraventricular impulses, paradoxically, resulted in normal
      intraventricular conduction. The phenomenon is a manifestation of supernormal LBB
      conduction, and only occurs following a wide QRS complex associated with
      retrograde activation of the LBB. The linking phenomenon reveals or unmasks the
      supernormal phase of LBB conduction. Following a retrograde and delayed
      activation of the LBB, the refractory period of the bundle branch is postponed,
      in such a way that a supraventricular impulse is allowed to occur during the
      early phase of supernormal conduction.

PMID- 1383985
TI  - Failure of defibrillator paddle as mimic for subcutaneous patch lead during
      nonthoracotomy implantable cardioverter defibrillator lead configuration
      assessment.
AB  - It is a common, although virtually unsubstantiated, practice to assess the
      efficacy of nonthoracotomy lead systems for implantable cardioverter
      defibrillators using a defibrillator paddle as mimic for the subcutaneous patch
      lead. We report a case in which an adequate defibrillation threshold was
      documented with the nonthoracotomy lead system using a defibrillator paddle but
      not following implantation of the true subcutaneous patch lead. This case
      suggests that the substitution of a defibrillator paddle for the subcutaneous
      patch lead during nonthoracotomy lead system evaluation may have significant
      limitations in assessing lead configuration efficacy.

PMID- 1383986
TI  - Programmable external automatic antitachycardia pacing as a bridge to definitive
      therapy in patients with recurrent sustained ventricular tachycardia.
AB  - The efficacy and safety of external programmable automatic antitachycardia
      pacemakers (ATPs) used in the critical care setting for recurrent sustained
      monomorphic ventricular tachycardia (VT) was evaluated. Ten patients who had
      failed a mean of 4.0 +/- 1.4 antiarrhythmic medications (range 2-7) and who had
      previously required electrical cardioversion for VT were enrolled. Prior to ATP
      use, successful overdrive pacing termination of VT was demonstrated in all
      patients. Intertach (Intermedics, Inc.; n = 9) and Orthocor II (Cordis, Inc.; n =
      1) ATPs were attached to temporary bipolar transvenous or epicardial pacing
      leads. Mean patient age was 66.4 +/- 11.5 years, and mean left ventricular
      ejection fraction was 22 +/- 7.5%. At the time of initial ATP use, mean VT cycle
      length was 347 +/- 88 msec (range 280-550 msec). A burst scanning antitachycardia
      pacing algorithm was used in each patient; one patient was also treated with a
      fixed rate burst adapted to VT cycle length. The duration of ATP use ranged from
      2-25 days (median 5), successfully terminating greater than 3,369 VT episodes
      (median 3, range 0 to greater than 3,103 episodes per-patient). Two episodes of
      ATP induced rate acceleration occurred, each successfully terminated by the ATP.
      Only two patients required external cardioversion during ATP use, one for primary
      ventricular fibrillation and one for rapid polymorphic VT associated with
      antiarrhythmic drug withdrawal. ATPs also provided antibradycardia pacing and
      allowed for serial programmed ventricular stimulation. No complications were
      associated with transvenous catheter or ATP use.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1383987
TI  - Radiofrequency ablation of bilateral quadruple accessory pathways in a patient
      with Wolff-Parkinson-White syndrome.
AB  - A patient with drug refractory supraventricular tachycardia showed
      electrophysiological evidence of bilateral quadruple accessory pathways. The
      conduction was bidirectional in the left posteroseptal and left posterolateral
      accessory pathways, antegrade in the right lateral accessory pathway, and
      retrograde in the right anterior accessory pathway. The four pathways
      participated in seven types of reciprocating tachycardias. Radiofrequency
      ablation eliminated the four pathways successfully. The patient was asymptomatic
      and free of any drug during a 10-month follow-up.

PMID- 1383988
TI  - Comparison of clinical benefits and outcome in patients with programmable and
      nonprogrammable implantable cardioverter defibrillators.
AB  - Technological advances in implantable cardioverter defibrillators (ICDs) have
      provided a variety of programmable parameters and antitachycardia therapies whose
      utility and impact on clinical outcome is presently unknown. ICDs have
      capabilities for cardioversion defibrillation alone (first generation ICDs), or
      in conjunction with demand ventricular pacing (second generation ICDs), or with
      demand pacing and antitachycardia pacing (third generation ICDs). We examined the
      pattern of antitachycardia therapy use and long-term survival in 110 patients
      with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).
      Group I included 62 patients with nonprogrammable first generation ICDs that
      delivered committed shock therapy after ventricular tachyarrhythmia detection
      based on electrogram rate and/or morphology was satisfied. Group II included 48
      patients with multiprogrammable ICDs (including second and third generation ICDs)
      that had programmable tachyarrhythmia detection based on rate and tachycardia
      confirmation prior to delivery of electrical treatment with either programmable
      shocks and/or, as in the third generation ICDs, antitachycardia pacing. Incidence
      and patterns of antitachycardia therapy use and long-term survival were compared
      in the two groups. The incidence of appropriate shocks in patients who completed
      1 year of follow-up was significantly greater in group I (30 of 43 patients = 70%
      vs 11 of 26 patients = 42%; P less than 0.05). In the total follow-up period, a
      significantly larger proportion of group I patients as compared to group II
      patients used the shock therapies (46 of 62 patients = 74% vs 25 of 48 patients =
      52%; P less than 0.01), with the majority doing so within the first year of
      implantation (96% and 92%, respectively). Although the frequency of
      antitachycardia therapy activation was similar, the number of shocks delivered
      per patient was lower in group II, particularly in the initial 3 months of follow
      up (P = 0.06). No clinical variable aided in identifying users from nonusers of
      antitachycardia therapy. Arrhythmic mortality was virtually eliminated in both
      groups. Two-year actuarial cardiac survival in the two groups was similar (group
      I = 78% vs group II = 84%; P greater than 0.2). Survival from cardiac mortality
      in users and nonusers of antitachycardia therapies was also similar in both
      groups (P greater than 0.2) and in the total patient group (P greater than 0.2).
      We conclude that programmable ICDs continue to confer advantages in prevention of
      sudden death that were observed with nonprogrammable ICDs and can be expected to
      improve patient tolerance and physician acceptance of device therapy for VT/VF.

PMID- 1383989
TI  - Histologic findings of the heart and the conduction system in the first patient
      who underwent catheter ablation.
AB  - This is a detailed pathological examination of the heart including the conduction
      system (CS) from a 64-year-old male who had catheter ablation of the
      atrioventricular (AV) junction for intractable atrial fibrillation. This is the
      world's first human who had this procedure, and who survived 3 years and 8
      months, and later died of congestive heart failure. Pathologically, the heart was
      hypertrophied and enlarged. Histologically, there were chronic inflammatory
      cells, marked fatty metamorphosis with fibrosis of the atria, the approaches to
      the AV node, and the AV node, with almost isolation of the node from the atria,
      and considerable fibrosis of the bundle and bundle branches. In addition, there
      was fibrosis of the summit of the ventricular septum with chronic inflammatory
      cells. These represent the sequelae of the ablation procedures. It is not known
      how much of the pathological findings contributed to the cardiac hypertrophy and
      impairment of cardiac function.

PMID- 1383990
TI  - Distinct activation patterns of idioventricular rhythms and sympathetically
      induced ventricular tachycardias in dogs with atrioventricular block.
AB  - To investigate mechanisms of ventricular impulse formation in response to
      sympathetic stimulation in the healthy canine heart in situ, we compared the
      patterns of ventricular activation during the idioventricular rhythms arising
      after complete atrioventricular (AV) block and ventricular tachycardias induced
      by RSG or LSG stimulation. Isochronal maps were generated by computer from 116
      127 unipolar electrograms recorded from the entire ventricular epicardium in 15
      open chest, anesthetized dogs. In eight of these, bipolar electrograms were
      recorded with plunge electrodes from 11 selected endocardial sites located below
      epicardial breakthrough areas. Intracardiac recordings from the His-Purkinje
      system were made with electrode catheters. After electrograms were recorded
      during sinus rhythm, complete AV block was induced by injecting formaldehyde into
      the AV node and idioventricular rhythms occurred spontaneously at a rate of 37 +/
      12 beats/min (mean +/- SD, n = 25). During idioventricular rhythms, endocardial
      activation preceded the earliest epicardial breakthrough, which occurred in
      either the right anterior paraseptal region, antero-apical left ventricle, or
      postero-apical left ventricle. These sites were consistent with a focal origin in
      the subendocardial His-Purkinje system. Total epicardial activation times lasted
      for 47 +/- 13 msec (n = 40). Idioventricular rhythms were suppressed by overdrive
      pacing (intermittent trains of ten beats with decremental cycle length from 500
      to 200 msec) or by intravenous calcium infusion (to plasma levels of 10.1-15.2
      mM). Right or left stellate ganglion stimulation increased idioventricular rhythm
      rates (to 52 +/- 13 beats/min, n = 28) and also induced, in all preparations,
      ventricular tachycardias that had significantly faster rates (189 +/- 55
      beats/min, n = 27, P less than 0.005). Ventricular fibrillation was induced after
      brief runs of ventricular tachycardia in five of the preparations. During
      ventricular tachycardias, epicardial activation occurred on the right ventricular
      outflow tract or the postero-lateral wall of the left ventricle, and preceded
      endocardial activation in 50% of cases. Total epicardial activation times (103 +/
      29 beats/min) were significantly longer than during idioventricular rhythms (P
      less than 0.005). Ventricular tachycardias displayed overdrive excitation at
      critical pacing cycle lengths (360-280 msec) and were not suppressed by calcium
      infusion. Thus, differential mechanisms of impulse formation with distinct
      localizations can be elicited from healthy ventricular myocardium.

PMID- 1383991
TI  - MATIC--an intracardiac tachycardia classification system.
AB  - The use of an additional atrial sensing electrode together with a morphology
      recognition algorithm provides a significant improvement in classification
      performance over the current rate based algorithms used in implantable
      cardioverter defibrillator (ICD) devices. The classification system, called
      morphology and timing intracardiac classifier (MATIC), follows a classification
      process similar to that used by cardiologists. Timing between the atrial and
      ventricular channels is examined using a decision tree and forms the primary
      criterion for arrhythmia classification. A neural network based morphology
      classifier is used for cases such as ventricular tachycardia with 1:1 retrograde
      conduction where timing alone cannot make a reliable decision. MATIC achieves
      99.6% correct classification on a database of intracardiac electrogram (ICEG)
      signals containing 12,483 QRS complexes recorded from 67 patients during
      electrophysiological studies. Arrhythmias in this database include sinus
      tachycardia, normal sinus rhythm, normal sinus rhythm with bundle branch block,
      sinus tachycardia with bundle branch block, atrial fibrillation (AF), various
      supraventricular tachycardias, ventricular tachycardia, ventricular tachycardia
      with 1:1 retrograde conduction, and ventricular fibrillation. Within these
      arrhythmias, there were numerous ventricular ectopic beats, fusion beats, noise,
      and other artifacts. MATIC addresses the classification problem from start to
      finish, inputs being raw intracardiac electrogram signals and the outputs being
      the recommended ICD therapy. Results achieved with MATIC were compared with a
      classifier used in the Telectronics Guardian ATP 4210, which achieved 75.9%
      correct classification on the same database. MATIC is simple and efficient,
      making it suitable for use in a low power implantable device.

PMID- 1383992
TI  - Atrial fibrillation: epidemiology and the risk and prevention of stroke.
AB  - Atrial fibrillation is a common disorder and the incidence increases with each
      decade of life. Previously, rheumatic mitral valve disease has been the condition
      most highly associated with atrial fibrillation. However, with the decreasing
      incidence of rheumatic heart disease, other conditions have assumed greater
      importance and now congestive cardiac failure, coronary artery disease, and
      hypertension are the most commonly associated conditions. Nonrheumatic atrial
      fibrillation is associated with an approximately five-fold increase in the risk
      of ischemic stroke and a 5% to 7% yearly risk that increases with age. In
      addition, atrial fibrillation is associated with an increased incidence of silent
      cerebral infarction and increased mortality. However, whether atrial fibrillation
      is independently associated with the risk of stroke or is a marker of underlying
      cardiac disease is contentious. Until recently, the use of preventive therapy has
      been controversial. However, data from four recently published, prospective
      randomized studies clearly support the use of warfarin prophylaxis in
      nonrheumatic atrial fibrillation. Within the diverse group of patients with
      nonrheumatic atrial fibrillation there are high and low risk subgroups and
      identification of these may influence decisions regarding antithrombotic
      prophylaxis. With a few exceptions, however, this remains an area in which there
      are contradictory findings in the literature. The role of aspirin for prophylaxis
      in nonrheumatic atrial fibrillation remains unclear and further evaluation awaits
      the publication of ongoing studies.

PMID- 1383993
TI  - Local area networks.

PMID- 1383994
TI  - A case of hidden receptacle-adapter incompatibility.
AB  - Connection of a universal VS-1 adapter to a VS-1 receptacle resulted in
      intermittent loss of pacing and of sensing in a pacemaker dependent patient. This
      was caused by the use of an adapter that only provides stable electric contact if
      the adapter pin is deformed by the set screw. Since we had implanted a pulse
      generator with a "side-lock" connector without screws, only a loose connection
      was achieved. The manufacturers should provide information on such hidden
      incompatibilities.

PMID- 1383995
TI  - A case of pacemaker lead fracture associated with weightlifting.

PMID- 1383996
TI  - Safe introducer technique for pacemaker lead implantation.

PMID- 1383997
TI  - Surgical treatment of ventricular tachycardia with Nd:YAG laser photocoagulation.
AB  - BACKGROUND: Directed surgery for the definitive treatment of drug resistant
      ventricular tachycardia (VT) due to coronary artery disease carries a significant
      operative mortality. Surgical failure to cure VT remains a problem, especially in
      patients without anterior left ventricular myocardial infarcts and aneurysms. A
      method has been developed in which Nd:YAG laser is used to photocoagulate
      myocardium responsible for the initiation of VT using a "sequential" approach
      intended to improve operative results and gain insight into the variable
      substrates causing VT. METHODS: Under normothermic cardiopulmonary bypass, VT is
      induced and then extensive endocardial and epicardial mapping performed to
      localize and characterize that form of VT. Nd:YAG is applied to the areas of
      myocardium from which that form of VT originates until it disappears and is no
      longer inducible. Next attempts are made to induce other forms of VT and when
      successful, mapping and lasing repeated until finally VT is no longer inducible.
      RESULTS: Fifty-one patients were operated on and have been followed for at least
      1 year. Operative mortality in 12 patients with preoperative ejection fractions
      less than 20% was 41%; in 39 patients with ejection fractions greater than 20%
      operative mortality was 8%. Eighty-eight percent of the 43 operative survivors
      are free of recurrent sustained VT at 1 year. There have been no arrhythmic
      mortalities. In a group of 30 patients evaluated for epicardial VT, 9 of 14
      patients with inferior infarcts without left ventricular aneurysms had at least
      one form of epicardial VT. CONCLUSIONS: Nd:YAG laser photocoagulation of
      myocardial VT using a sequential approach is a viable method that permits an
      ongoing study of this entity. Operative mortality remains high in patients with
      diffusely poor left ventricular function. Epicardial VT is frequent in patients
      with inferior infarcts and may account for inferior results in these patients
      when conventional endocardial approaches are used alone.

PMID- 1383998
TI  - The nonpharmacological treatment of tachyarrhythmias--towards a new therapeutic
      era.

PMID- 1383999
TI  - Transcoronary chemical ablation of arrhythmias.
AB  - BACKGROUND: Chemical or electrical ablation of an arrhythmogenic ventricular area
      and the atrioventricular (AV) node is still an experimental technique. After we
      introduced alcohol ablation in the clinical situation we conducted this study to
      develop the catheter technique for delivering alcohol in patients with incessant
      ventricular tachycardia after myocardial infarction and patients with atrial
      fibrillation and flutter with uncontrollable ventricular rates. METHODS: In
      patients with incessant ventricular tachycardia, the coronary artery supplying
      blood to the site of origin of the tachycardia could be identified by the
      combined information from coronary and left ventricular angiography and from
      programmed electrical stimulation, including endocardial mapping and pace
      mapping. In the 12 patients with incessant ventricular tachycardia we selected,
      the coronary artery supplying blood to the site of origin of the tachycardia
      could be identified and catheterized in ten patients. Ethanol ablation was
      successful in all of them. With a follow-up from 2 to 44 months, seven of the ten
      treated patients are still alive and six remain free of tachycardia. In patients
      with atrial fibrillation or flutter and uncontrollable ventricular rates, the AV
      artery could be catheterized and ethanol injected in 13 of the 19 patients.
      Complete block was produced in ten patients and AV conduction was sufficiently
      modified to control symptoms in three patients. Long-term results with ethanol
      ablation have remained excellent in this setting. CONCLUSION: Chemical ablation
      is a technique that may be of enormous value and even lifesaving for patients
      with an incessant form of tachycardia not responding to any form of medical
      therapy. Transcoronary ablation of AV conduction should be considered in patients
      with a right dominant coronary circulation in whom radiofrequency ablation has
      failed.

PMID- 1384000
TI  - The idiopathic long QT syndrome: therapeutic management.

PMID- 1384001
TI  - Radiofrequency catheter ablation of accessory pathways.
AB  - One hundred five patients with an accessory atrioventricular pathway underwent
      catheter ablation of the pathway using radiofrequency current. There were 79
      accessory pathways located on the left and 32 on the right side of the heart. In
      patients with right-sided pathways ablation was attempted via a catheter
      positioned at the atrial aspect of the tricuspid annulus. In patients with a left
      sided free-wall accessory pathway a novel approach was utilized in which the
      ablation catheter was positioned in the left ventricle directly below the mitral
      annulus. Accessory pathway conduction was permanently abolished in 93 patients
      (89%). Failures were mainly due to inadequate catheters used initially. It is
      concluded that catheter ablation of accessory atrioventricular pathways using
      radiofrequency current is an effective and safe therapeutic modality for patients
      with symptomatic tachyarrhythmias mediated by these pathways.

PMID- 1384002
TI  - Behavioral states and sudden cardiac death.
AB  - Remarkable progress has been made both experimentally and clinically in defining
      the influence of behavioral states on susceptibility to life-threatening
      arrhythmias. Biological models have been developed to emulate anger and fear and
      have permitted detailed study of the intermediary mechanisms involved in stress
      induced ischemia and ventricular fibrillation. The studies highlight the
      importance of adrenergic factors and the pathological significance of the
      poststress state. Clinically, the role of daily stresses in inducing silent
      myocardial ischemia and arrhythmias has been extensively characterized, and
      standardized behavioral stress tests have become available. Certain sleep states
      have been found to provoke ischemic episodes and arrhythmias. In particular,
      phasic rapid eye movement (REM) sleep has been shown both in animals and humans
      to conduce to perfusion abnormalities and propensity to fibrillation. Episodic
      surges in sympathetic nervous system activity appear to be the underlying basis.
      These conceptual and practical advances illustrate the promise of behavioral
      cardiology in the diagnosis and treatment of individuals at risk for sudden
      cardiac death.

PMID- 1384003
TI  - Three decades of antiarrhythmic therapy.
AB  - Over the last several decades there has been an impressive expansion in the study
      and management of cardiac arrhythmias. New developments in diagnostic and
      interventional clinical electrophysiology as well as research at the cellular
      tissue and whole heart levels have improved our understanding of the mechanisms
      of arrhythmias and have allowed the development of new and effective treatment
      modalities. During the 1960s (Early Decade-Enabling) the first lifesaving
      measures such as cardiac resuscitation, external defibrillation, and temporary
      pacing were introduced in the new coronary care units. Cardiac catheterization
      and reproducible techniques for recording of intracardiac potentials were
      developed. The decade of 1970 to 1980 (Middle Decade-Diagnosis) was characterized
      by the development of programmed stimulation for initiation and termination of
      arrhythmias. This represented a real revolution in clinical cardiology that led
      to the understanding of the nature of several tachyarrhythmias and related them
      to experimental mechanisms of arrhythmogenesis. In the same decade, two other
      diagnostic tools emerged for assessing cardiac arrhythmias and monitoring the
      efficacy of antiarrhythmic drug therapy: ambulatory ECG monitoring and exercise
      testing. In addition, the impact of antiarrhythmic drugs on ionic currents was
      studied and drug classifications based on these properties appeared. The decade
      1980-1990 (Recent Decade-Therapy), witnessed the development of interventional
      electrophysiology techniques such as transcatheter ablation, and the use of
      cardiac surgery for the ablation of arrhythmogenic substrates. Another major
      advance was the design of implantable devices capable of recognizing
      tachyarrhythmias and treating them by programmed stimulation or defibrillation
      shocks. In parallel, the efficacy and safety of antiarrhythmic drugs has been
      reassessed and new compounds are being developed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1384004
TI  - Life-threatening tachyarrhythmias in athletes.
AB  - The arrhythmias in competitive athletes may be classified as "benign,"
      "paraphysiological" due to prolonged athletic training, or "pathological" due to
      hemodynamic effects on the athletic performance-risk-arrhythmogenic substratum.
      Pathological arrhythmias include life-threatening forms that are severe enough to
      produce symptoms (presyncope, syncope, cardiac arrest) during athletic activity.
      These forms are in particular rapid VT, VF, torsades de pointes, preexcited
      atrial fibrillation, sinus atrial and AV block. Our study population includes 766
      competitive athletes, mean age 21.1 years (74 top international level),
      investigated with a cardioarrhythmological work-up for symptoms and for
      arrhythmias from 1974 to June 30, 1991. Three leading categories, represented by
      16 aborted sudden death, 8 sudden death, and 7 induced VF (by EES or TAP)
      athletes, are described. All athletes with life-threatening arrhythmias,
      previously as asymptomatic or with minor symptoms had an arrhythmogenic
      substratum due to underlying silent cardiopathy or primary arrhythmic disorders.
      Athletic activity can be regarded as a trigger of electrical destabilization.

PMID- 1384005
TI  - [Expression of HLA-DR antigens by colonic epithelium in ulcerative colitis].
AB  - Expression of HLA-DR antigens by colon epithelium was examined in 35 patients
      with ulcerative colitis (uc) among whom 21 were in relapse and 14 in remission.
      Control group consisted of 18 subjects with functional disorders of alimentary
      tract. Immunohistochemical technique using immunoperoxidase was applied. Colon
      epithelial cells from all control subjects were HLA-DR negative. Cells of 17 out
      of 21 patients with ulcerative colitis in relapse and in 4 of 14 patients in
      remission were HLA-DR positive. No significant correlation was observed between
      the number of patients with HLA-DR positive epithelium and the insensitive of
      inflammation estimated clinically, endoscopically and histologically. 6 patients
      with initially HLA-DR positive epithelium during relapse were studied for the
      second time and in 4 of them the negative reaction was observed after remission
      occurred. The aberrant expression of HLA-DR may play an important role in the
      initiation and/or perpetuation of inflammatory process in ulcerative colitis.

PMID- 1384006
TI  - Galanin and calcitonin gene-related peptide immunoreactivity in nerves of the rat
      uterus: localization, colocalization, and effects on uterine contractility.
AB  - Immunoreactivity to the neuropeptides galanin (GAL) and calcitonin gene-related
      peptide (CGRP) was examined in nerves in the rat uterus as a prelude to studying
      their effects on uterine contractility. With immunocytochemical techniques, GAL
      immunoreactivity (GAL-I) and CGRP-I were localized in myometrial nerves
      throughout the uterine horns and cervix, with nerves immunoreactive for CGRP
      being more numerous. Immunocytochemical double-labeling studies revealed GAL
      coexists with CGRP in a subpopulation of CGRP-I nerve fibers, i.e., GAL-I was not
      present in all CGRP-I nerves. Effects of these neuropeptides on uterine
      contractility were examined on in vitro preparations of uterine horns from
      diethylstilbestrol-treated rats. GAL (10(-5) to 10(-8) M) stimulated uterine
      contraction in a dose-related manner. CGRP had no effect on basal uterine
      tension, but CGRP (10(-7) M) reduced GAL-stimulated (10(-7) M) uterine
      contraction by 92.5%. These results demonstrate that GAL- and CGRP-I are present
      in, and coexist in, some uterine nerves, presumably afferent nerves. GAL and CGRP
      could be released from afferent fibers in an "efferent fashion" and influence
      uterine contractility, GAL having a contractile effect and CGRP having a relaxing
      effect.

PMID- 1384007
TI  - Metabolic effects of galanin injections into the paraventricular nucleus of the
      hypothalamus.
AB  - The metabolic effects of single injections of galanin into the paraventricular
      nucleus of the hypothalamus (PVN) were investigated in an open-circuit
      calorimeter. Wistar rats were tested, with no food available during the tests. In
      the dose range of 0.03-0.3 nmol, galanin produced a very short-latency
      (approximately 2 minutes) and short-lasting (approximately 15 minutes) reduction
      in energy expenditure. Since the same doses had no effect on respiratory quotient
      or locomotor activity, the metabolic effect is not secondary to changes in energy
      substrate utilization or locomotor activity. This antithermogenic effect
      complements the eating stimulatory action of PVN galanin, and together these
      phenomena suggest a role for galanin as an anabolic neuropeptide. The similarity
      of galanin's effects to those of norepinephrine, with which it coexists in PVN
      nerve endings, further suggests the involvement of this amine and the PVN alpha2
      noradrenergic system in galanin's mechanism of action.

PMID- 1384008
TI  - Galanin inhibits adenylate cyclase of rat brain membranes.
AB  - The ubiquitous neuropeptide, galanin, strongly inhibits adenylate cyclase in rat
      brain membranes. While basal enzyme activity was not altered, galanin from 10(
      11) M to 5 x 10(-7) M decreased forskolin- and VIP-stimulated adenylate cyclase
      with a half-maximal effect being elicited by 0.7 nM neuropeptide and a maximal
      80% inhibition of the enzyme activity. The galanin fragments (2-29) and (1-15)
      dose-dependently inhibited the forskolin-stimulated adenylate cyclase, while the
      fragments (3-29) and (10-29) were found inactive. These results indicate that the
      regulatory action of galanin in the central nervous system involves the coupling
      of galanin receptors to the inhibition of the adenylate cyclase system.

PMID- 1384009
TI  - Bovine pancreatic trypsin inhibitor and homologous polypeptide inhibitors in
      nephron cells.
AB  - Bovine pancreatic trypsin inhibitor (BPTI, aprotinin) is a fifty-eight amino acid
      polypeptide, which is present together with related molecular isoforms in various
      bovine organs. In the present study these protease inhibitors were isolated from
      bovine kidney by affinity chromatography on immobilized trypsin and a subsequent
      FPLC step. Due to their electrophoretic, structural, and inhibitory properties,
      the inhibitors were strictly similar to the polypeptides identified previously in
      other bovine organs. Immunohistochemical experiments showed a widespread
      localization of these polypeptides in nephron epithelial cells (proximal and
      distal tubules, loop of Henle, collecting tubules).

PMID- 1384010
TI  - Possible existence of a new tachykinin receptor subtype in the guinea pig ileum.
AB  - The guinea pig ileum possesses NK-1 and NK-3 tachykinin receptors. As expected,
      [Pro9]SP and senktide, which are selective agonists of NK-1 and NK-3 receptors,
      respectively, were found to be highly potent in contracting the guinea pig ileum.
      Surprisingly, similar observations were made with septide, SP-O-CH3, [Apa9-10]SP,
      or [Pro9,10]SP although, in contrast to [Pro9]SP, these four peptides showed a
      low affinity for 3H-[Pro9]SP-specific NK-1 binding sites on membranes from the
      guinea pig ileum. They were also devoid of affinity for NK-2 and NK-3 binding
      sites. GR 71251, a compound which has been described as a NK-1 antagonist, was
      more potent in inhibiting the septide- than the [Pro9]SP-evoked contracting
      response. Altogether, these results suggest that septide, [Apa9-10]SP, and
      [Pro9,10]SP exert their high contracting activity in the guinea pig ileum by
      acting on a new subtype of tachykinin receptors.

PMID- 1384011
TI  - [Activity of selected proteinase inhibitors in patients with disorders of lipid
      metabolism].
AB  - The study was aimed at verification of previously found, in animals with
      experimentally induced atherosclerosis, the disturbances of serum proteinases
      inhibitors: alpha-2-antiplasmin, alpha-1-antitrypsin and alpha-2-macroglobulin.
      In humans with hypercholesterolemia the decrease of serum activity of alpha-2
      antiplasmin was observed. In humans with hypercholesterolemia and increased serum
      concentration of triacylglycerols no significant changes in activity of alpha-1
      antitrypsin and alpha-2-macroglobulin were found--in comparison with control
      subjects.

PMID- 1384012
TI  - Chromaticity analysis of immunostained tumor specimens.
AB  - In order to evaluate the correlation between immunohistochemical and morphometric
      data on the same histological sections, we have developed a flexible color image
      analyzer (Microcomputer-Assisted Picture Processing System type II, MAPPS-II),
      and established an effective method to analyze the immunostained colorectal
      neoplasms based on the color recognition theory of human visual system.
      Colorectal adenomas and adenocarcinomas were stained with a monoclonal antibody C
      12, which recognizes abnormal H antigen, using Avidin-Biotin method and
      diaminobenzidine (DAB, brown dye). Nuclei were stained with Hematoxylin (blue
      dye). Density and colorimetric analyses revealed two results: (A) Separation of
      immunostained brown area from blue nuclei was best performed by plotting the
      representative sample areas on a standard chromaticity diagram, which displays
      the hue and saturation of colors simulating color of human visual system. (B)
      After separation of immunostained areas, usual density analysis was useful for
      the assay of nuclear morphometric information. Using these programs, normal
      mucosa was negative for C 12, and showed low nuclear/cytoplasmic ratio (NCR).
      Adenoma was occasionally focally positive for C 12, and showed medium NCR.
      Carcinomas were C 12 positive, and showed high NCR. Our method permits nuclear
      counterstaining by hematoxylin instead of low contrast methyl green, which will
      widen the field of combined immunohistochemical and morphometric study.

PMID- 1384013
TI  - NK cell activity in treated prostate cancer patients as a probe for circulating
      tumor cells: hormone regulatory effects in vivo.
AB  - Natural killer (NK) cell activity was studied together with tumor marker
      serotests (PSA, PAP) and blood testosterone, estradiol, cortisol, and prolactin
      concentrations in treated prostate cancer patients. NK cell activity data were
      correlated with tumor stage (stage D0 + D1 versus stage D2) and showed
      statistically insignificant differences. Both tumor progression and stabilization
      of metastatic disease, triggered by the application of more appropriate therapy
      in progressive subjects, yielded low NK activity data. By contrast, normal NK
      activity was found during both partial remission of stage D2 tumor and
      stabilization of the same disease, after an initial period of tumor remission.
      Differences between NK activity data from the aforementioned two groups are
      statistically significant (P less than 0.01). In subjects examined, the
      application of NK activity assay to those with advanced disease reflected changes
      in the outcome of the treatment more closely than it did routine tumor marker
      assessment. The activity of NK cells seems unaffected by changes in basal blood
      estradiol, cortisol, testosterone, and prolactin concentrations that occur during
      therapy with pharmacological agents (estradiol, cyproterone acetate,
      diethylstilbestrol, and flutamide) and during surgical castration. The reported
      NK activity recordings in treated prostate cancer patients might be indicative of
      the presence of tumor cells in the circulation. If this holds true, the
      measurement of NK activity would appear to furnish urological oncology with a new
      tool for early, rapid recognition of progressive metastatic tumors.

PMID- 1384014
TI  - Regulation of prostatic carcinoma cell proliferation and secretory activity by
      extracellular matrix and stromal secretions.
AB  - Previous studies from our laboratory have shown that reconstituted basement
      membrane and stromal secretory products are important regulators of benign
      prostatic epithelial cell growth and differentiation. In the present study we
      evaluated the impact of extracellular matrix (ECM) and soluble stromal secretory
      products on the proliferation and secretory activity of the androgen-responsive
      prostatic carcinoma cell line LNCaP. In these studies, dihydrotestosterone (DHT)
      was a potent mitogen for LNCaP cells cultured on plastic or on type I collagen.
      The growth response to DHT was greatly attenuated when LNCaP cells were grown on
      prostatic stromal ECM. Cells grown on stromal ECM also exhibited clustered
      morphology compared to the monolayer growth observed on plastic and secreted
      elevated levels of prostate specific antigen (PSA) and prostatic acid phosphatase
      (PAP). These findings indicate that cultivation of LNCaP on stromal ECM will
      promote the expression of differentiated functions. In additional studies,
      stromal cell conditioned medium (SCM) significantly increased PSA/PAP secretion
      by LNCaP cells in the presence of 10 nM DHT. The enhancement of DHT-induced
      PSA/PAP secretion by SCM was most pronounced when LNCaP cells were grown on
      stromal ECM. SCM did not significantly alter LNCaP proliferation. These studies
      indicate that prostatic stromal ECM and soluble secretory products will promote
      differentiated function in cultured LNCaP cells. In addition, we show that DHT
      can act as either a growth or differentiation-promoting stimulus depending on the
      presence of stromal factors.

PMID- 1384015
TI  - Prostate-specific antigen: establishment of the reference range for the
      clinically normal prostate gland and the effect of digital rectal examination,
      ejaculation, and time on serum concentrations.
AB  - This study investigated the serum prostate-specific antigen concentration in 100
      healthy men (mean age, 26.3 years; range, 20-29 years) with a clinically normal
      prostate gland. The effect of digital rectal examination and ejaculation on the
      serum concentration, and the variability of the serum concentration over 1-week
      and 1-month periods were examined. In the 100 subjects, the serum prostate
      specific antigen concentration ranged from less than 0.1-2.6 ng/ml. The mean,
      median, and mode were 0.68 ng/ml, 0.6 ng/ml, and 0.4 ng/ml, respectively. The
      97.5th percentile value was 2.1 ng/ml. The mean and median changes in the serum
      concentration after digital rectal examination were -0.013 +/- 0.11 ng/ml and 0.0
      ng/ml, respectively (P = 0.59 compared with control group). The mean change after
      ejaculation was 0.05 +/- 0.12 ng/ml, and the median change was 0.0 ng/ml (P =
      0.14 compared with control group). Diurnal variation showed minimal change in 16
      patients over a 1-week period. The mean change (p.m. value-a.m. value) was 0.003
      ng/ml (range, -0.2-0.06 ng/ml). In addition, the serum concentration showed
      minimal intrapatient variability in 20 patients throughout a 1-month period; the
      average coefficient of variation (standard deviation/mean) in these subjects was
      16.5% (range, 6.4-45.2%). These results indicate that the range in the serum
      concentration of prostate-specific antigen for healthy men with a clinically
      normal prostate gland is significantly lower (0.0-2.6 ng/ml) than the currently
      employed range (0.0-4.0 ng/ml; Tandem-R PSA assay); in addition, digital rectal
      examination and ejaculation have no significant effect on the serum
      concentration. Finally, the time of day has little effect, and the variability in
      the serum concentration of prostate-specific antigen over a 1-week and 1-month
      interval is minimal.

PMID- 1384016
TI  - Mesothelial and related neoplasms in children and adolescents: a
      clinicopathologic and immunohistochemical analysis of eight cases.
AB  - Mesothelioma is a neoplasm that occurs infrequently in childhood; only an
      estimated 2-5% of all cases present in the first two decades of life. The
      diagnosis may be perplexing because of its rarity and its pathologic similarities
      to other papillary or spindle cell neoplasms in the pediatric age group. We have
      studied eight cases of mesothelial or submesothelial-derived neoplasms of pleural
      (four cases) and peritoneal (four cases) origin in patients 4 to 17 years of age
      at diagnosis. Microscopically, six were epithelial, with papillary,
      tubuloglandular, and solid patterns. Two tumors were predominantly fibrous
      appearing, one a localized pleural fibroma and the other a diffuse pleural
      sarcomatoid mesothelioma. All of the tumors were immunoreactive for vimentin, and
      all except the pleural fibroma stained for either cytokeratin, epithelial
      membrane antigen, or both. None reacted with antibodies to carcinoembryonic
      antigen, placental alkaline phosphatase, or Leu-M1. At last follow-up, three
      patients were dead of tumor, three were alive and well, and two had been recently
      diagnosed and were undergoing treatment. These results indicate that the
      immunohistochemical profile delineated for mesothelioma in adults is equally
      applicable to mesothelial neoplasms in younger patients and is useful in
      establishing a diagnosis. The prognosis for malignant mesothelioma in childhood
      appears to be as unfavorable as the adult counterpart, with the possible
      exceptions of certain clinicopathologic subtypes.

PMID- 1384017
TI  - Undifferentiated small cell hepatoblastoma with a unique chromosomal
      translocation: a case report.
AB  - Cytogenetic studies of pediatric tumors have revealed a number of reproducible
      karyotypic abnormalities, including del(p13) found in aniridia-Wilms' tumor
      association, t(8;14) in Burkitt's lymphoma, and t(11;22) in Ewing's sarcoma. To
      date, no consistent cytogenetic abnormality has been reported in association with
      hepatoblastoma. We report the case of a 7-month-old male infant with the
      undifferentiated small cell variant of hepatoblastoma. Immunohistochemistry
      revealed reactivity with antibodies to cytokeratin and vimentin throughout the
      tumor. Alpha-fetoprotein, neuron-specific enolase, and S100 stains were negative.
      Chromosomal analysis of metaphase cells from a culture of tumor tissue revealed a
      translocation of most of the long arm of chromosome 22 to the distal long arm of
      chromosome 10.

PMID- 1384018
TI  - Endomyocardial biopsy approach in cases with ventricular arrhythmias.
AB  - Right ventricular endomyocardial biopsies were performed in patients with
      ventricular tachycardia (VT: n = 20) and idiopathic premature ventricular
      contraction (PVC: n = 23). Active myocarditis was found in one case and
      postmyocarditic change in 9 cases. Significant pathology according to our
      definition was found in 9 out of the total of 43 cases (20.5%). The pathological
      features of the 9 cases were interstitial fibrosis in 5, disarrangement of muscle
      bundles in 6, degeneration of myocytes in one and increase in fatty tissue in 7.
      Increase in fatty tissue was characteristically observed in 6 out of the 20 cases
      with VT and it was noteworthy that the VT cases with left bundle branch block
      configuration showed high incidence of the fatty tissue (5/12 cases, 42%).

PMID- 1384019
TI  - Standard indication of immunotherapy for the treatment of cancer.

PMID- 1384020
TI  - In vitro solubilization of deposits of IgG immune complexes by gamma-globulins in
      patients with Graves' disease, Graves' ophthalmopathy, pretibial myxoedema and
      Hashimoto's thyroiditis.

PMID- 1384021
TI  - Effects of Bacillus subtilis spores on interferon production.

PMID- 1384022
TI  - Effects of piroxicam and ibuprofen on substance P induced chemotaxis of human
      monocytes and polymorphonuclear cells.

PMID- 1384023
TI  - Inosine pranobex in the combination therapy of HIV infection.

PMID- 1384024
TI  - The interferons: biological bases for clinical strategies.

PMID- 1384025
TI  - Use of interferon in chronic viral hepatitis.

PMID- 1384027
TI  - Conjunctival penetration of insulin and peptide drugs in the albino rabbit.
AB  - An in vitro model was used to evaluate the conjunctival penetration of three
      peptides, [D-ala2]metenkephalinamide (YAGFM, MW 647), substance P (MW 1348), and
      insulin (MW 5778), in comparison with two nonpeptides, atenolol (MW 266) and
      timolol (MW 433). All three peptides were hydrolyzed to varying extents during
      penetration across the conjunctiva. The permeability coefficient for intact YAGFM
      and insulin was 4.5 +/- 0.3 and 4.6 +/- 0.7 microns sec-1, respectively. These
      values were about two to five times lower than those for atenolol and timolol. No
      permeability coefficient could be calculated for substance P, since its
      transconjunctival flux never reached steady state. The conjunctival penetration
      of YAGFM and insulin was improved by about two and three times, respectively,
      with the addition of 1% Na glycocholate. Increasing the Na glycocholate
      concentration was more effective than changing the type of bile salt in improving
      the conjunctival penetration of insulin. The maximum factor of improvement was
      12, as the Na glycocholate concentration was raised to 4%. The way in which Na
      deoxycholate, glycocholate, and taurocholate affected the conjunctival
      penetration of atenolol, timolol, and insulin suggests that these three bile
      salts improved mainly the transcellular penetration of the compounds studied.

PMID- 1384029
TI  - Molecular weight-dependent lymphatic transfer of exogenous macromolecules from
      large intestine of renal insufficiency rats.
AB  - To study the lymphatic delivery of exogenous macromolecules via the enteral route
      in renal insufficiency, we determined the transfer selectivity to the systemic
      blood and lymph of fluorescein isothiocyanate-labeled dextrans of different
      average molecular weight (10, 18, 39, and 69kD). The compounds were administered
      into the large intestinal lumen of rats with occluded renal circulation, with the
      aid of lipid-surfactant mixed micelles as an absorption prometer. Whereas
      concentrations of the smaller dextrans (molecular weight under 18 kD) in the
      lymph of the thoracic duct and in the peripheral plasma were similar, levels of
      dextrans over 39 kD were significantly higher in the lymph than in the plasma.
      Further, dextran plasma concentrations decreased in inverse proportion to
      increasing molecular weight. The molecular weight threshold for a high lymph-to
      blood level ratio (18-39 kD) was higher than that previously found in rats with
      normal renal function (10-18 kD). This difference was accounted for by reduced
      renal clearance of the low molecular weight dextrans in renal failure. These
      results are useful in the design of lymphotropic drug delivery in disease states.

PMID- 1384028
TI  - Antisense c-myc oligodeoxyribonucleotide cellular uptake.
AB  - Antisense oligonucleotides have therapeutic potential as inhibitors of gene
      expression. However, the mechanism by which an intact oligonucleotide reaches the
      intracellular site of action is unknown. In this study, we use an
      oligodeoxyribonucleotide 21-mer complementary to the translation initiation codon
      of the c-myc protooncogene to study the mechanism of oligonucleotide uptake and
      internalization into Rauscher Red 5-1.5 cells. We find trypsin-sensitive and
      trypsin-insensitive surface binding, in addition to internalization. Uptake is
      partially energy dependent and inhibited by charged molecules, including DNA,
      ATP, a random sequence oligonucleotide, and dextran sulfate. Uptake does not
      appear to occur via a traditional receptor-mediated uptake pathway because
      chloroquine, monensin, and phenylarsine oxide pretreatment does not significantly
      decrease internalization. An anion channel inhibitor, SITS, and the salts, NaCl,
      Na2SO4, and NH4Cl, significantly decrease oligonucleotide uptake. Whether uptake
      occurs via a channel or a novel uptake mechanism is still unknown. A model is
      proposed which reasonably simulates the experimental data.

PMID- 1384026
TI  - Anti-AIDS drug development: challenges and strategies.
AB  - A myriad of chemical derivatives has been shown to inhibit in vitro replication
      of the AIDS virus at concentrations that are nontoxic to the host cells. The
      majority of these agents acts by either (i) inhibiting enzymes such as reverse
      transcriptase (RT), protease, or glucosidase, (ii) arresting expression of genes
      or gene products, or (iii) inhibiting viral processes such as giant cell
      (syncytia) formation or viral binding to the target cell. The nucleoside RT
      inhibitors are the most widely studied agents at both the preclinical and the
      clinical levels. Their inability to cure AIDS has stimulated the discovery of
      several novel nonnucleoside RT inhibitors, possessing varied structures and
      demonstrating activity at nanomolar concentrations. These agents demonstrate a
      unique mode of binding to RT and show a high specificity for HIV-1. Protease
      inhibitors, soluble CD4 derivatives, oligonucleotides, and many anionic
      derivatives also demonstrate potent anti-HIV-1 activities. These derivatives
      possess mechanisms of action different to the nucleosides and exhibit selectivity
      as exemplified by their high in vitro therapeutic indices. This article discusses
      the structural parameters that govern activity in these agents, the pros and cons
      regarding the development of these compounds as putative anti-AIDS agents, and
      the future promise of searching for newer agents directed at novel targets to
      inhibit the AIDS virus.

PMID- 1384030
TI  - Membrane glycoproteins common to vesicles and melanosomes in mouse melanoma
      cells.

PMID- 1384031
TI  - Folding in vitro of bovine pancreatic trypsin inhibitor in the presence of
      proteins of the endoplasmic reticulum.
AB  - The rates of folding and disulfide bond formation in reduced BPTI were measured
      in vitro in the presence and absence of total protein from the endoplasmic
      reticulum. The rates were increased substantially by the endoplasmic reticulum
      proteins, but only to the extent expected from the known content and activity of
      protein-disulfide-isomerase. No effects of added ATP or Ca2+ were observed, even
      though protein-disulfide-isomerase binds Ca2+ tightly.

PMID- 1384032
TI  - Empirical solvation models in the context of conformational energy searches:
      application to bovine pancreatic trypsin inhibitor.
AB  - Continuum solvation models that estimate free energies of solvation as a function
      of solvent accessible surface area are computationally simple enough to be useful
      for predicting protein conformation. The behavior of three such solvation models
      has been examined by applying them to the minimization of the conformational
      energy of bovine pancreatic trypsin inhibitor. The models differ only with regard
      to how the constants of proportionality between free energy and surface area were
      derived. Each model was derived by fitting to experimentally measured equilibrium
      solution properties. For two models, the solution property was free energy of
      hydration. For the third, the property was NMR coupling constants. The purpose of
      this study is to determine the effect of applying these solvation models to the
      nonequilibrium conformations of a protein arising in the course of global
      searches for conformational energy minima. Two approaches were used: (1) local
      energy minimization of an ensemble of conformations similar to the equilibrium
      conformation and (2) global search trajectories using Monte Carlo plus
      minimization starting from a single conformation similar to the equilibrium
      conformation. For the two models derived from free energy measurements, it was
      found that both the global searches and local minimizations yielded conformations
      more similar to the X-ray crystallographic structures than did searches or local
      minimizations carried out in the absence of a solvation component of the
      conformational energy. The model derived from NMR coupling constants behaved
      similarly to the other models in the context of a global search trajectory. For
      one of the models derived from measured free energies of hydration, it was found
      that minimization of an ensemble of near-equilibrium conformations yielded a new
      ensemble in which the conformation most similar to the X-ray determined structure
      PTI4 had the lowest total free energy. Despite the simplicity of the continuum
      solvation models, the final conformation generated in the trajectories for each
      of the models exhibited some of the characteristics that have been reported for
      conformations obtained from molecular dynamics simulations in the presence of a
      bath of explicit water molecules. They have smaller root mean square (rms)
      deviations from the experimentally determined conformation, fewer incorrect
      hydrogen bonds, and slightly larger radii of gyration than do conformations
      derived from search trajectories carried out in the absence of solvent.

PMID- 1384033
TI  - Variability of conformations at crystal contacts in BPTI represent true low
      energy structures: correspondence among lattice packing and molecular dynamics
      structures.
AB  - The structures of five basic pancreatic trypsin inhibitor (BPTI) molecules are
      compared to establish the extent and nature of the conformational variability
      resulting from crystal packing effects. BPTI is an ideal system to evaluate such
      factors because of the availability of high resolution X-ray models of five
      different BPTI structures, each in a different crystal packing environment.
      Differences observed among the structures are found to be distributed throughout
      the molecule, although the regions that display most variability are associated
      with the loop structures (residues 14-17 and 24-29). The regions of structure
      that show the largest rms deviations from the mean of the five packing motifs
      correlate well with the presence of intermolecular contacts in the crystal
      lattice. For most of the molecules there is also a correspondence between a
      larger number of intermolecular contacts and systematically higher B-factors,
      although it is not apparent whether this is induced by the crystal contact or
      results from the fact that the contacts are made predominantly through surface
      loops. The conformational differences seen among the X-ray models constitute more
      than local shifts at the lattice contact surfaces, and in fact involve in some
      cases the making and breaking of intramolecular H-bonds. The magnitudes of the
      differences among packing models are significantly larger than those usually
      associated with changes induced by mutagenesis; for instance; the structural
      differences at the site of mutation observed on removing an internal disulfide
      from the molecule are significantly less than those associated with lattice
      contact effects. The crystal packing conformations are compared to representative
      structures of BPTI generated during a 96-psec molecular dynamics (MD) simulation.
      This comparison shows a high level of correspondence between the protein
      flexibility indicated by the X-ray and MD analyses, and specifically between
      those regions that are most variable. This suggests that the regions that show
      most variability among the crystal packing models are not artifacts of
      crystallization, but rather represent true low-energy conformers that have been
      preferentially selected by crystallization factors.

PMID- 1384034
TI  - Structural effects induced by mutagenesis affected by crystal packing factors:
      the structure of a 30-51 disulfide mutant of basic pancreatic trypsin inhibitor.
AB  - The X-ray structure of the C30V/C51A disulfide mutant of basic pancreatic trypsin
      inhibitor (BPTI) has been analyzed at 1.6 A resolution. The mutant crystallizes
      in a cell having two molecules in the asymmetric unit. The packing environments
      of these two molecules are quite different, allowing for an assessment of which
      among the observed structural changes result from the mutation and which are
      produced by lattice packing considerations. The removal of the 30-51 disulfide
      bridge has little apparent affect on the B-factors of segments of adjacent
      polypeptide chain, although there are distinct differences in the structure
      compared to wild-type BPTI crystal structures. Both of the two C30V/C51A
      molecules show differences at the mutation site when compared to another 30-51
      disulfide mutant, C30A/C51A, presumably due to the larger steric bulk of a valine
      versus an alanine at residue 30. A comparison of the two independent C30V/C51A
      molecules indicates that there are significant differences between them even at
      the site of mutation. The description of the specific structural differences of
      each molecule differs in detail and suggests different conclusions about the
      nature of structural perturbation near 30-51. In addition, when these two
      molecules are compared to two different wild-type structures, which had been
      determined from different space groups, a somewhat different pattern of changes
      is observed. These findings indicate that crystal packing can influence the
      observed perturbations in mutant structures.

PMID- 1384035
TI  - In vitro selection of an RNA epitope immunologically cross-reactive with a
      peptide.
AB  - An antiserum raised against a peptide was used to select a unique RNA species
      from a degenerate pool of RNAs designed to resemble an autoantibody recognition
      site in U1 RNA. The peptide and the selected RNA epitope could compete for
      antibody binding, suggesting that both RNA and peptide epitopes occupy the same
      or overlapping antigen-combining sites. Thus, the RNA epitope functioned as a
      specific inhibitor of the antibody-antigen interaction. We demonstrate that the
      RNA epitope can be used to tag unrelated RNA molecules and also to detect the
      presence of the antibody. We propose that sequence-specific recognition of RNA by
      antibodies may involve protein-RNA contacts similar to those occurring in other
      nucleic acid-binding proteins. In addition, these findings are compatible with
      the suggestion that nucleic acid-binding autoantibodies may arise through
      immunological cross-reactivity between proteins and nucleic acids.

PMID- 1384036
TI  - Major histocompatibility complex determinants select T-cell receptor alpha chain
      variable region dominance in a peptide-specific response.
AB  - Dominant expression of T-cell receptor (TCR) alpha or beta chain variable region
      (V alpha or V beta) gene families has been observed in the T-cell response to
      some conventional peptide antigens. Current models for the interaction of TCR V
      region elements with different determinants of a major histocompatibility complex
      (MHC)-peptide complex, the normal TCR ligand, suggest that the TCR V-J junctional
      region (CDR3, where J is joining) is the primary contact with a peptide epitope
      and that other TCR V region segments may interact directly with neighboring MHC
      determinants. This suggests that V alpha or V beta dominance in a specific
      response can be MHC-selected. In this case, if related peptides bind to an MHC
      molecule in a similar orientation, they could select for identical V alpha or V
      beta dominance even if they are noncrossreactive at the level of T-cell
      activation. We have screened for this possibility by introducing minimal
      conservative substitutions in a synthetic peptide, YYEELLKYYEELLK, that is
      presented to T cells in association with an uncommon A beta E alpha d mixed Ia
      isotype. We report here that the peptide variant FFEELLKFFEELLK is
      noncrossreactive with YYEELLKYYEELLK but appears to preserve the same MHC binding
      motif since T-cell responses are restricted to the same mixed A beta E alpha
      isotype. Although the two peptides are noncrossreactive in either direction, the
      same members of the V alpha 4 gene family are dominantly expressed in T cells
      specific for either peptide. We conclude that the similar topography of the two
      MHC-peptide complexes gives functional significance to a unique A beta E alpha
      determinant that selects for V alpha 4 dominance.

PMID- 1384037
TI  - GreA protein: a transcription elongation factor from Escherichia coli.
AB  - A protein identified as the 158-amino acid product of the greA gene was isolated
      from Escherichia coli. When added to a halted ternary transcription complex, the
      GreA protein induced cleavage and removal of the 3' proximal dinucleotide from
      the nascent RNA. The new 3' terminus generated by the cleavage could be extended
      into longer transcripts. GreA-mediated cleavage of a transcript appears to permit
      a ternary complex to resume transcription from a state of indefinite elongation
      arrest induced by a specific DNA site. The GreA protein tended to interact with
      RNA polymerase during purification and recycled between RNA polymerase molecules
      in the course of the in vitro cleavage reaction. Similar biochemical activities
      have been reported in eukaryotic RNA polymerases, indicating that transcript
      cleavage and restart of elongation may be a general transcriptional mechanism.

PMID- 1384038
TI  - Spatial pattern of receptor expression in the olfactory epithelium.
AB  - A PCR-based strategy for amplifying putative receptors involved in murine
      olfaction was employed to isolate a member (OR3) of the seven-transmembrane
      domain receptor superfamily. During development, the first cells that express OR3
      appear adjacent to the wall of the telencephalic vesicle at embryonic day 10. The
      OR3 receptor is uniquely expressed in a subset of olfactory cells that have a
      characteristic bilateral symmetry in the adult olfactory epithelium. This
      receptor and its specific pattern of expression may serve a functional role in
      odor coding or, alternatively, may play a role in the development of the
      olfactory system.

PMID- 1384039
TI  - Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2
      and two SH3 domains, from human and rat cDNA libraries.
AB  - The protein ASH (for abundant Src homology), composed of one Src homology region
      (SH) 2 and two SH3 domains, was cloned by screening human and rat cDNA libraries
      with an oligonucleotide probe directed to a consensus sequence of the SH2
      domains. The rat-derived ASH peptide was comprised of 217 amino acids with a
      molecular mass of 25-28 kDa and was found to be ubiquitous in rat tissues. A
      human cDNA clone was also found to code for part of the same protein, suggesting
      that ASH is common to human and rat. The amino acid sequence of ASH was
      strikingly similar to Sem-5, the product of a nematode cell-signaling gene, and
      ASH is most probably a mammalian homologue of Sem-5. ASH bound in vitro to
      phosphotyrosine-containing proteins, including activated epidermal growth factor
      receptor, the ASH SH2 domain being responsible for the binding. Induced
      expression of an antisense ASH cDNA led to a reduction in cell growth.
      Considering these observations and the structural homology to Sem-5, ASH is
      likely to function as a ubiquitous signal transducer, possibly resembling Sem-5,
      which communicates between a receptor protein tyrosine kinase and a Ras protein.

PMID- 1384040
TI  - Cis-acting, orientation-dependent, positive control system activates pheromone
      inducible conjugation functions at distances greater than 10 kilobases upstream
      from its target in Enterococcus faecalis.
AB  - The prgB gene encodes the surface protein, Asc10, which mediates cell
      aggregation, resulting in high-frequency conjugative transfer of the pheromone
      inducible tetracycline-resistance plasmid pCF10 in Enterococcus faecalis.
      Messenger RNA analysis by Northern blot hybridization and primer extension
      indicates that prgB transcription is pheromone-inducible and monocistronic.
      Previous transposon mutagenesis and sequencing analysis of a 12-kilobase (kb)
      region of pCF10 indicated that several genes including prgR and prgS are required
      to activate expression of prgB. The distance (3-4 kb) between these regulatory
      genes and prgB suggested that the activation might function in trans. To test
      this, a promoterless lacZ gene fusion to prgB was constructed and cloned without
      some or all of the regulatory genes. Several restriction fragments of the
      regulatory region were cloned in a higher copy-number plasmid, and numerous
      complementation studies were carried out in E. faecalis. Complementation in trans
      was not observed in any of these experiments. However, when the regulatory region
      and target genes were cloned in different sites of the same plasmid, separated by
      as much as 12 kb, activation of prgB was observed. Interestingly, this activation
      occurred only when the regions were cloned in the same relative orientation in
      which they exist on wild-type pCF10. These results suggest that one or more
      regulatory molecules may bind to an upstream cis-acting site and track along the
      DNA to reach a target site to activate prgB transcription.

PMID- 1384042
TI  - Interaction with basement membrane serves to rapidly distinguish growth and
      differentiation pattern of normal and malignant human breast epithelial cells.
AB  - Normal human breast epithelial cells show a high degree of phenotypic plasticity
      in monolayer culture and express many traits that otherwise characterize tumor
      cells in vivo. Paradoxically, primary human breast carcinoma cells are difficult
      to establish in culture: most outgrowths arise from the normal tissue surrounding
      the tumor. These characteristics have posed major obstacles to the establishment
      of simple reliable criteria for mammary epithelial transformation in culture. In
      the present study, we show that a reconstituted basement membrane (BM) can be
      used to culture all normal human breast epithelial cells and a subset of human
      breast carcinoma cells. The two cell types can be readily distinguished by virtue
      of the ability of normal cells to reexpress a structurally and functionally
      differentiated phenotype within BM. Twelve specimens of normal breast tissue and
      2 normal breast epithelial cell lines (total 14 samples) embedded in BM as single
      cells were able to form multicellular spherical colonies with a final size close
      to that of true acini in situ. Sections of mature spheres revealed a central
      lumen surrounded by polarized luminal epithelial cells expressing keratins 18 and
      19 and sialomucin at the apical membrane. Significantly, two-thirds of normal
      spheres deposited a visible endogenous type IV collagen-containing BM even though
      they were in contact with exogenously provided BM. Growth was arrested completely
      within the same time period. In contrast, none of 6 carcinoma cell lines or 2
      cultures of carcinoma from fresh samples (total 8 samples) responded to BM by
      growth regulation, lumen formation, correct polarity, or deposition of endogenous
      BM. These findings may provide the basis of a rapid assay for discriminating
      normal human breast epithelial cells from their malignant counterparts.
      Furthermore, we propose that the ability to sense BM appropriately and to form
      three-dimensional organotypic structures may be the function of a class of
      "suppressor" genes that are lost as cells become malignant.

PMID- 1384041
TI  - Integrins as a primary signal transduction molecule regulating monocyte immediate
      early gene induction.
AB  - Integrins are cell surface receptors found on monocytes that facilitate adhesion
      to both cellular and extracellular substrates. These integrins are thought to be
      involved in the selective gene induction observed after monocyte adhesion to
      various extracellular matrices. To investigate this hypothesis, we stimulated
      monocytes with monoclonal antibodies to different integrin receptors to
      specifically mimic the integrin receptor-ligand interactions. Engagement of the
      common beta chain of the beta 1 subfamily of integrins resulted in expression of
      the inflammatory mediator genes, interleukin 1 beta, interleukin 1 receptor
      antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas
      engagement of the common beta chain of the beta 2 family did not. Furthermore, to
      characterize integrin-mediated gene induction, we examined the ability of
      antibodies to the alpha chain of integrin receptors to regulate gene expression.
      Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of
      all the mediator genes. Receptor crosslinking was required because individual Fab
      fragments were unable to stimulate gene induction whereas the divalent F(ab')2
      fragment and the whole IgG molecule could. Interleukin 1 beta secretion was
      dependent on the anti-integrin antibody used. Some antibodies required a second
      signal and, for others, direct engagement was sufficient for protein production.
      In conclusion, engagement of integrin receptors regulated the production of both
      inflammatory mediator mRNA and protein. These results suggest that integrin
      dependent recognition and adherence may provide the key signals for initiation of
      the inflammatory response during monocyte diapedesis.

PMID- 1384043
TI  - Activation of phosphatidylinositol 3-kinase by epidermal growth factor, basic
      fibroblast growth factor, and nerve growth factor in PC12 pheochromocytoma cells.
AB  - Epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and nerve
      growth factor (NGF), which stimulate the phosphorylation of proteins on tyrosine
      in PC12 cells, initiate these modifications through ligand-specific cell surface
      receptors that contain the causative tyrosine kinases. One apparent substrate for
      these enzymes is phosphatidylinositol 3-kinase (PI 3-kinase), an enzyme that
      phosphorylates the D-3 position of the inositol ring and associates with several
      protein tyrosine kinases, as indicated by the fact that it is immunoprecipitated
      from EGF-, bFGF-, and NGF-stimulated PC12 cells by an anti-phosphotyrosine
      antibody. All three growth factors increase immunoprecipitable PI 3-kinase
      activity after 2 min of addition at concentrations able to stimulate either
      mitogenic or neurotrophic responses in PC12 cells. The level of stimulation of PI
      3-kinase activity by EGF, bFGF, and NGF is 15- to 20-fold, 2- to 3-fold, and 8-
      to 10-fold, respectively. Moreover, tyrosine phosphorylation of PI 3-kinase was
      detected in EGF-, bFGF-, and NGF-stimulated PC12 cells, and the amount of the
      phosphorylation correlated with the level of stimulation of enzyme activity. In
      contrast, phosphatidylinositol 4-kinase, which produces the inositol
      phospholipids cleaved by phospholipase C-gamma to yield diacylglycerol and
      inositol-1,4,5-trisphosphate, is not affected by these growth factors. The
      pattern of stimulation of PI 3-kinase does not correlate with the induction of
      neurite outgrowth but rather with the mitotic responses, suggesting that PI 3
      kinase and its products may be more important for signaling in cell division than
      in trophic processes. However, the levels of phosphatidylinositol 3-phosphate do
      not coincide with the stimulation of [3H]thymidine incorporation by these growth
      factors, rendering its role in mitotic functions, at least in PC12 cells, also
      uncertain.

PMID- 1384044
TI  - D1-dopamine receptors activate c-fos expression in the fetal suprachiasmatic
      nuclei.
AB  - The existence of an activatable dopamine system within the hypothalamic
      suprachiasmatic nuclei (SCN), the site of a biological clock, was investigated in
      rats during fetal life. In situ hybridization studies revealed that D1-dopamine
      receptor mRNA was highly expressed in the fetal SCN and not expressed in other
      hypothalamic regions. Cocaine injected into pregnant rats or directly into rat
      fetuses on day 20 of gestation selectively activated c-fos gene expression in the
      fetal SCN; cocaine did not induce c-fos expression elsewhere in the fetal brain
      or in the maternal SCN. This cocaine-induced activation of c-fos expression in
      fetal SCN was mediated in part through D1-dopamine receptors, as the cocaine
      induced activation was partially blocked by the D1-dopamine receptor antagonist
      SCH 23390. In addition, the selective D1-dopamine receptor agonist SKF 38393
      induced high levels of c-fos expression in the fetal SCN. The presence of an
      activatable dopamine system within the fetal SCN provides a mechanism through
      which maternal signals could entrain the fetal biological clock and through which
      maternally administered psychotropic drugs could alter normal development of the
      circadian timing system.

PMID- 1384045
TI  - Higher plant Ca(2+)-ATPase: primary structure and regulation of mRNA abundance by
      salt.
AB  - Calcium-dependent regulatory mechanisms participate in diverse developmentally,
      hormonally, and environmentally regulated processes, with the precise control of
      cytosolic Ca2+ concentration being critical to such mechanisms. In plant cells, P
      type Ca(2+)-ATPases localized in the plasma membrane and the endoplasmic
      reticulum are thought to play a central role in regulating cytoplasmic Ca2+
      concentrations. Ca(2+)-ATPase activity has been identified in isolated plant cell
      membranes, but the protein has not been characterized at the molecular level. We
      have isolated a partial-length cDNA (LCA1) and a complete genomic clone (gLCA13)
      encoding a putative endoplasmic reticulum-localized Ca(2+)-ATPase in tomato. The
      deduced amino acid sequence specifies a protein (Lycopersicon Ca(2+)-ATPase) of
      1048 amino acids with a molecular mass of 116 kDa, eight probable transmembrane
      domains, and all of the highly conserved functional domains common to P-type
      cation-translocating ATPases. In addition, the protein shares approximately 50%
      amino acid sequence identify with animal sarcoplasmic/endoplasmic reticulum
      Ca(2+)-ATPases but less than 30% identity with other P-type ATPases. Genomic DNA
      blot hybridization analysis indicates that the Lycopersicon Ca(2+)-ATPase is
      encoded by a single gene. RNA blot hybridization analysis indicates the presence
      of three transcript sizes in root tissue and a single, much less abundant,
      transcript in leaves. Lycopersicon Ca(2+)-ATPase mRNA levels increase
      dramatically upon a 1-day exposure to 50 mM NaCl. Thus this report describes the
      primary structure of a higher-plant Ca(2+)-ATPase and the regulation of its mRNA
      abundance by salt stress.

PMID- 1384046
TI  - Identification and prevalence of a genetic defect that causes leukocyte adhesion
      deficiency in Holstein cattle.
AB  - Two point mutations were identified within the gene encoding bovine CD18 in a
      Holstein calf afflicted with leukocyte adhesion deficiency (LAD). One mutation
      causes an aspartic acid to glycine substitution at amino acid 128 (D128G) in the
      highly conserved extracellular region of this adhesion glycoprotein, a region
      where several mutations have been found to cause human LAD. The other mutation is
      silent. Twenty calves with clinical symptoms of LAD were tested, and all were
      homozygous for the D128G allele. In addition, two calves homozygous for the D128G
      allele were identified during widespread DNA testing, and both were subsequently
      found to exhibit symptoms of LAD. The carrier frequency for the D128G allele
      among Holstein cattle in the United States is approximately 15% among bulls and
      6% among cows. This mutation is also prevalent among Holstein cattle throughout
      the world, placing this disorder among the most common genetic diseases known in
      animal agriculture. All cattle with the mutant allele are related to one bull,
      who through the use of artificial insemination sired many calves in the 1950s and
      1960s. The organization of the dairy industry and the diagnostic test described
      herein will enable nearly complete eradication of bovine LAD within 1 year. These
      results also demonstrate that bovine LAD is genetically homologous and
      phenotypically similar to human LAD, thus providing a useful animal model for
      studies of LAD and beta 2 integrin function.

PMID- 1384047
TI  - Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor
      like protein with distinct ligand specificity.
AB  - A cDNA that expresses a receptor for very low density lipoprotein (VLDL) was
      isolated from a rabbit heart cDNA library and characterized. The deduced amino
      acid sequence of the cDNA revealed that the cDNA encodes a protein with striking
      homology to the low density lipoprotein (LDL) receptor. Like the LDL receptor,
      the mature protein consists of the following five domains spanning 846 amino
      acids: 328 N-terminal amino acids including an 8-fold repeat of 40 amino acids
      homologous to the ligand binding repeat of the LDL receptor; 396 amino acid
      residues homologous to the epidermal growth factor precursor including three
      cysteine-rich repeats; a region immediately outside of the plasma membrane rich
      in serines and threonines; 22 amino acids traversing the plasma membrane; and 54
      amino acids including the NPVY sequence that is required for clustering of the
      LDL receptor in coated pits and that projects into the cytoplasm. LDL-receptor
      deficient Chinese hamster ovary cells transfected with the cDNA bound and
      internalized VLDL, beta-migrating VLDL, and intermediate density lipoprotein but
      did not bind LDL with high affinity. The 3.6- and 9.5-kilobase mRNAs for the VLDL
      receptor are highly abundant in heart, muscle, and adipose tissue. Barely
      detectable amounts of the mRNAs were present in liver. Based on the structural
      features, ligand specificity, and tissue expression of the mRNAs, we suggest that
      this VLDL receptor may mediate uptake of apolipoprotein E-containing lipoproteins
      enriched with triglyceride in nonhepatic tissues that are active in fatty acid
      metabolism.

PMID- 1384048
TI  - mu-crystallin is a mammalian homologue of Agrobacterium ornithine cyclodeaminase
      and is expressed in human retina.
AB  - mu-Crystallin is the major component of the eye lens in several Australian
      marsupials. The complete sequence of kangaroo mu-crystallin has now been obtained
      by cDNA cloning. The predicted amino acid sequence shows similarity with
      ornithine cyclodeaminases encoded by the tumor-inducing (Ti) plasmids of
      Agrobacterium tumefaciens. Until now, neither ornithine cyclodeaminase nor any
      structurally related enzymes have been observed in eukaryotes. RNA analysis of
      kangaroo tissues shows that mu-crystallin is expressed at high abundance in lens,
      but outside the lens mu-crystallin is preferentially expressed in neural tissues,
      retina, and brain. An almost full-length cDNA for mu-crystallin was cloned from
      human retina. In human tissues, mu-crystallin mRNA is present in neural tissue,
      muscle, and kidney. This pattern of expression and relationship to an enzyme
      involved in unusual amino acid metabolism suggests the interesting possibility
      that mammalian mu-crystallins could be enzymes participating in processes such as
      osmoregulation or the metabolism of excitatory amino acids.

PMID- 1384049
TI  - CD5 acts as a tyrosine kinase substrate within a receptor complex comprising T
      cell receptor zeta chain/CD3 and protein-tyrosine kinases p56lck and p59fyn.
AB  - T-cell antigens including CD2, CD4, CD6, CD8, and CD28 serve as coreceptors with
      the T-cell receptor (TCR)/CD3 complex in control of T-cell growth. The molecular
      basis by which these antigens fulfill this role has remained a major issue. An
      initial clue to this question came with our finding that the sensitivity of in
      vitro kinase labeling (specifically using protein-tyrosine kinase p56lck) allowed
      detection of a physical association between CD4-p56lck and the TCR/CD3 complexes.
      Another T-cell antigen, CD5, is structurally related to the macrophage scavenger
      receptor family and, as such, can directly stimulate and/or potentiate T-cell
      proliferation. In this study, we reveal that in Brij 96-based cell lysates, anti
      CD5 antibodies coprecipitated TCR zeta chain (TCR zeta)/CD3 subunits as well as
      the protein-tyrosine kinases p56lck and p59fyn. Conversely, anti-CD3 antibody
      coprecipitated CD5, p56lck, and p59fyn. Indeed, anti-CD5 and anti-CD3 gel
      patterns were virtually identical, except for a difference in relative intensity
      of polypeptides. Anti-CD4 coprecipitated p56lck, p32, and CD3/TCR zeta subunits
      but precipitated less CD5, suggesting the existence of CD4-TCR zeta/CD3 complexes
      distinct from the CD5-TCR zeta/CD3 complexes. Consistent with the formation of a
      multimeric CD5-TCR zeta/CD3 complex, anti-CD5 crosslinking induced tyrosine
      phosphorylation of numerous T-cell substrates, similar to those phosphorylated by
      TCR zeta/CD3 ligation. Significantly, as for TCR zeta, CD5 was found to act as a
      tyrosine kinase substrate induced by TCR/CD3 ligation. The kinetics of
      phosphorylation of CD5 (t1/2 = 20 sec) was among the earliest of activation
      events, more rapid than seen for TCR zeta (t1/2 = 1 min). CD5 represents a likely
      TCR/CD3-associated substrate for protein-tyrosine kinases (p56lck or p59fyn) and
      an alternative signaling pathway within a multimeric TCR complex.

PMID- 1384050
TI  - Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in
      vitro.
AB  - A panel of 20 recombinant Fab fragments reactive with the surface glycoprotein
      gp120 of human type 1 immunodeficiency virus (HIV-1) were examined for their
      ability to neutralize MN and IIIB strains of the virus. Neutralization was
      determined as the ability of the Fab fragments to inhibit infection as measured
      in both a p24 ELISA and a syncytium-formation assay. One group of closely
      sequence-related Fab fragments was found to neutralize virus in both assays with
      a 50% neutralization titer at approximately 1 micrograms/ml. Another Fab
      neutralized in the p24 ELISA but not in the syncytium assay. The other Fab
      fragments showed weak or no neutralizing ability. The results imply that virion
      aggregation or crosslinking of gp120 molecules on the virion surface is not an
      absolute requirement for HIV-1 neutralization. Further, all of the Fab fragments
      were shown to be competitive with soluble CD4 for binding to gp120 and yet few
      neutralized the virus effectively, implying that the mechanism of neutralization
      in this case may not involve receptor blocking. The observation of a
      preponderance of high-affinity Fab fragments with poor or no neutralizing ability
      could have implications for vaccine strategies.

PMID- 1384051
TI  - Expression patterns of gamma-aminobutyric acid type A receptor subunit mRNAs in
      primary cultures of granule neurons and astrocytes from neonatal rat cerebella.
AB  - Using a competitive polymerase chain reaction assay, we have quantitated the
      absolute amounts of mRNA encoding 14 distinct subunits of the gamma-aminobutyric
      acid type A (GABAA) receptor in primary cultures of rat cerebellar granule
      neurons and cerebellar astrocytes. We found that the total amount of GABAA
      receptor subunit mRNA in astrocytes was 2 orders of magnitude lower than in
      neuronal cells. Furthermore, granule cell cultures expressed all 14 different
      GABAA subunit mRNAs, while the astroglial cultures contained detectable amounts
      of all the subunits expressed by granule cells except the alpha 6 and the gamma
      2L subunits. Of the alpha subunit family members, the alpha 1, alpha 5, and alpha
      6 mRNAs were prominent in granule cells, while the alpha 1 and alpha 2 mRNAs were
      abundant in astrocytes. Of the beta receptor subunit mRNAs, the beta 1 and beta 3
      mRNAs were abundantly expressed in both cultures. The gamma 2S and gamma 2L mRNAs
      constituted the great majority of gamma subunit mRNAs in neurons, while the gamma
      1 subunit mRNA was the most abundant gamma subunit mRNA in astrocytes. When
      various allosteric modulators of GABAA receptors were tested
      electrophysiologically, methyl 6,7-dimethoxy-4-ethyl-beta-carboline- 3
      carboxylate (DMCM) was the only one to modulate chloride currents elicited by
      GABA in a significantly different manner in granule cells (negative modulation)
      compared with astrocytes (positive modulation). The latter effect was previously
      observed in transiently expressed recombinant GABAA receptors containing a gamma
      1 instead of a gamma 2 subunit. Our quantitative mRNA results suggest that an
      important molecular determinant responsible for the DMCM-positive modulatory
      effect on astroglial native GABAA receptors is the presence of the gamma 1
      subunit in the receptor assembly.

PMID- 1384052
TI  - A bifunctional enzyme (delta 1-pyrroline-5-carboxylate synthetase) catalyzes the
      first two steps in proline biosynthesis in plants.
AB  - Many plants synthesize and accumulate proline in response to osmotic stress.
      Despite the importance of this pathway, however, the exact metabolic route and
      enzymes involved in the synthesis of proline in plants have not been
      unequivocally identified. We report here the isolation of a mothbean (Vigna
      aconitifolia) cDNA clone encoding a bifunctional enzyme, delta 1-pyrroline-5
      carboxylate synthetase (P5CS), with both gamma-glutamyl kinase and glutamic-gamma
      semialdehyde dehydrogenase activities that catalyzes the first two steps in
      proline biosynthesis. The two enzymatic domains of P5CS correspond to the ProB
      and ProA proteins of Escherichia coli and contain a leucine zipper in each
      domain, which may facilitate inter- or intramolecular interaction of this
      protein. The Vigna P5CS enzyme activity is feedback regulated by proline but is
      less sensitive to end-product inhibition than is the E. coli gamma-glutamyl
      kinase. The P5CS gene is expressed at high levels in Vigna leaves and is
      inducible in roots subjected to salt stress, suggesting that P5CS plays a key
      role in proline biosynthesis, leading to osmoregulation in plants.

PMID- 1384053
TI  - A phylogenetic analysis of the myxobacteria: basis for their classification.
AB  - The primary sequence and secondary structural features of the 16S rRNA were
      compared for 12 different myxobacteria representing all the known cultivated
      genera. Analysis of these data show the myxobacteria to form a monophyletic
      grouping consisting of three distinct families, which lies within the delta
      subdivision of the purple bacterial phylum. The composition of the families is
      consistent with differences in cell and spore morphology, cell behavior, and
      pigment and secondary metabolite production but is not correlated with the
      morphological complexity of the fruiting bodies. The Nannocystis exedens lineage
      has evolved at an unusually rapid pace and its rRNA shows numerous primary and
      secondary structural idiosyncrasies.

PMID- 1384054
TI  - Radioprotection of mice by recombinant rat stem cell factor.
AB  - Treatment with recombinant rat stem cell factor (rSCF) protects mice from the
      lethal effects of irradiation. Mice treated with a single dose of rSCF prior to
      irradiation of up to 1150 rads [given as a split dose (1 rad = 0.01 Gy)] resulted
      in > 80% long-term survival, whereas a single injection given after the last dose
      of irradiation was not radioprotective. The combination of pre- and posttreatment
      (-20 h, -2 h, and +4 h) with rSCF resulted in 100% survival of otherwise lethally
      irradiated mice. Using this optimum schedule of rSCF administration, a
      radioprotective factor of 1.3-1.35 was achieved. The major cause of death in the
      control animals was massive bacteremia consisting of enteric organisms. The rSCF
      treated animals had a much lower frequency of septicemia, due primarily to a
      rapid hematopoietic recovery of bone marrow function not evident in control
      animals.

PMID- 1384055
TI  - High-resolution mapping of mammalian genes by in situ hybridization to free
      chromatin.
AB  - Fluorescence in situ hybridization to metaphase chromosomes or chromatin fibers
      in interphase nuclei is a powerful technique in mapping genes and DNA segments to
      specific chromosome region. We have been able to release the chromatin fibers
      from cells arrested at G1 and G2 phases using different drugs and a simple
      alkaline lysis procedure. We have also demonstrated specific hybridization of
      fluorescence-labeled probes to single-copy genomic DNA sequences on the free
      chromatins. Fluorescence in situ hybridization signals have been detected for
      sequences separated as close as 21 kilobase pairs and as far as 350 kilobase
      pairs, with excellent correspondence between the observed and expected distances.
      The resolution of this technique should approach 10 kilobase pairs and its
      coverage should span millions of base pairs. Therefore, free chromatin mapping
      can be generally used to study the structure and organization of mammalian
      genomes.

PMID- 1384056
TI  - Association of protein-tyrosine kinase with phospholipase C-gamma 1 in bone
      marrow-derived mouse mast cells.
AB  - Bone marrow-derived mouse mast cells contain phospholipase C-gamma 1 (PLC-gamma
      1), which is phosphorylated at tyrosine residues upon cross-linking of cell-bound
      IgE antibodies with multivalent antigen. It was found that immune complexes
      formed from digitonin lysates of the mast cells by monoclonal anti-PLC-gamma 1
      antibodies contained protein-tyrosine kinase (PTK), which phosphorylated PLC
      gamma 1 in vitro. The tyrosine kinase activity coprecipitated with PLC-gamma 1
      anti-PLC-gamma 1 complexes markedly increased when the cell lysates were obtained
      immediately after antigen challenge. The results indicate that PTK is associated
      with PLC-gamma 1 in the mast cells and that the kinase is activated upon cross
      linking of Fc epsilon RI. Neither beta nor gamma subunit of Fc epsilon RI nor src
      family PTK was coprecipitated with the PLC-gamma 1-anti-PLC-gamma 1 complexes. In
      situ denaturation/renaturation experiments, which detect autophosphorylated
      kinases, indicated that the PTK associated with PLC-gamma 1 was a 44-kDa protein.

PMID- 1384057
TI  - Direct analysis of the binding of Src-homology 2 domains of phospholipase C to
      the activated epidermal growth factor receptor.
AB  - A number of proteins involved in intracellular signaling contain regions of
      homology to the product of the src oncogene that are termed Src-homology (SH) 2
      domains. SH2 domains are believed to mediate the association of these proteins
      with various tyrosine-phosphorylated receptors in a growth factor-dependent
      manner. We have examined the kinetic characteristics of one of these
      interactions, the binding of the SH2 domains of phospholipase C gamma 1 with the
      receptor for epidermal growth factor (EGF). Bacterial fusion proteins were
      prepared containing the two SH2 domains of PLC gamma 1 and labeled metabolically
      with [35S]methionine/cysteine. A fusion protein containing both SH2 domains bound
      to the purified EGF receptor from EGF-treated cells, whereas no binding to
      receptors from control cells was detected. Binding was rapid, reaching apparent
      equilibrium by 10 min. Dissociation of the complex occurred only in the presence
      of excess unlabeled SH2 protein and exhibited two kinetic components. Similarly,
      analysis of apparent equilibrium binding revealed a nonlinear Scatchard plot,
      further indicating complex binding kinetics that may reflect cooperative
      behavior. The binding of the fusion protein containing both SH2 domains was
      inhibited by a fusion protein containing only the amino-terminal SH2 domain,
      although at concentrations an order of magnitude higher than that observed with
      the complete fusion protein. Fusion proteins containing SH2 domains from the
      GTPase-activating protein, the p85 regulatory subunit of phosphatidylinositol 3'
      kinase, or the Abl oncoprotein competed less effectively. Binding of the PLC
      gamma 1 SH2 fusion protein to a mutant EGF receptor lacking the two carboxyl
      terminal tyrosine phosphorylation sites exhibited a significantly lower affinity
      than that observed with the wild type, suggesting that this region of the
      receptor may play an important role. This binding assay represents a means with
      which to evaluate the pleiotropic nature of growth factor action.

PMID- 1384058
TI  - A fraction of the mRNA 5' cap-binding protein, eukaryotic initiation factor 4E,
      localizes to the nucleus.
AB  - The 5' cap structure m7GpppN (where N is any nucleotide) is a ubiquitous feature
      of cellular eukaryotic mRNAs. The cap is multifunctional as it is involved in
      translation, nucleocytoplasmic transport, splicing, and stabilization of mRNA
      against 5' exonucleolytic degradation. The cap binding protein, eukaryotic
      initiation factor 4E (eIF-4E), is a translation initiation factor that binds to
      the cap structure and is part of a complex (eIF-4F) that promotes mRNA binding to
      ribosomes. Overexpression of eIF-4E in fibroblasts results in cell
      transformation. To test the hypothesis that some of the biological effects of eIF
      4E might be effected by a nuclear function, we determined the cellular
      distribution of eIF-4E. By means of indirect immunofluorescence experiments using
      polyclonal and monoclonal antibodies against eIF-4E as well as transfected
      epitope-tagged eIF-4E, we demonstrate that a fraction of eIF-4E localizes to the
      nucleus. These results suggest that eIF-4E is also involved in a nuclear
      function.

PMID- 1384059
TI  - Reverse transcriptase of human immunodeficiency virus can use either human
      tRNA(3Lys) or Escherichia coli tRNA(2Gln) as a primer in an in vitro primer
      utilization assay.
AB  - Although the reverse transcriptase (RT) of human immunodeficiency virus (HIV)
      uses human tRNA(3Lys) as a primer of viral genome DNA synthesis in vivo, HIV RT
      binds Escherichia coli glutamine tRNA and in vitro-made human lysine tRNA with
      nearly equivalent affinities. We show that HIV RT can use either tRNA(3Lys) or
      tRNA(2Gln) as a primer for DNA synthesis in vitro without the addition of any
      other host or viral proteins. E. coli tRNA(2Gln) can serve as a primer for HIV RT
      if a primer-binding site sequence complementary to the 3' end of tRNA(2Gln) is at
      the 3' end of the template. With this reduced template, the specificity of
      binding the proper tRNA is due to base-pairing between a bound tRNA to the primer
      binding site of the viral RNA template rather than sequence-specific recognition
      of tRNA(3Lys) by RT. If an 8-nucleotide viral sequence 3' to the primer-binding
      site is included in the template, then addition of Zn2+ or Co2+ is required for
      tRNA(3Lys)-primed synthesis, and tRNA(2Gln) now fails to prime synthesis. The
      latter result implies that a template sequence adjacent to the primer-binding
      site and containing 6 nucleotides complementary to the anticodon loop of human
      tRNA(3Lys) plays an active role in tRNA discrimination.

PMID- 1384060
TI  - Regulation of the reverse transcriptase of human immunodeficiency virus type 1 by
      dNTPs.
AB  - Reverse transcriptase (RNA-directed DNA polymerase, EC 2.7.7.49) of human
      immunodeficiency virus type 1 has been examined with respect to the steady-state
      kinetics of polymerization of dNTPs into product DNA. With dNTPs as variable
      substrate, the kinetics of polymerization deviated from standard Michaelis-Menten
      kinetics. Substrate inhibition was observed at high substrate concentrations and
      negative cooperativity was seen at lower substrate concentrations. Examination of
      incorporation of substrate dNMPs in the presence of nucleotides not complementing
      the template demonstrated that dNTPs may act as noncompetitive inhibitors, as
      well as substrate. The Ki of the enzyme for dNTPs was 104 microM. A working model
      is presented that accounts for the substrate inhibition. In this model, the
      reverse transcriptase is a multisubunit holoenzyme, where noncompetitive
      inhibition is mediated by one subunit binding nucleotide and down-regulating the
      enzymatically active 64-kDa subunit. With additional assumptions, this model can
      accommodate the negative cooperativity observed.

PMID- 1384062
TI  - Antirepression function in Escherichia coli for the cAMP-cAMP receptor protein
      transcriptional activator.
AB  - The cAMP receptor protein (CRP) complex (cAMP-CRP) is a global regulator of gene
      expression. It influences transcription from a number of promoters in Escherichia
      coli, including two divergently oriented promoters in the pap pili-adhesin gene
      system. To further define the role of cAMP-CRP in pap regulation we monitored
      protein-DNA interactions in vitro and levels of pap transcription in vivo in wild
      type and mutant pap-containing clones. The results showed that activation was
      mediated by a single cAMP-CRP-binding site centered at nucleotide positions 
      215.5 and -115.5 relative to the transcriptional start points. A target for the
      pap-specific regulatory protein PapB was localized adjacent to the cAMP-CRP
      binding site. The long-range effects exerted from the protein-binding sites were
      consistent with the idea that cAMP-CRP caused a change in the local DNA
      conformation and that a nucleoprotein complex (involving cAMP-CRP and PapB) was
      formed in the region between the pap promoters. Moreover, transcription became
      independent of activation of cAMP-CRP and the PapB protein in a mutant lacking
      the nucleoid-associated protein H-NS. Our findings suggest that the cAMP-CRP
      complex mediates its positive regulatory function by alleviating transcriptional
      silencing and, as such, plays a role as antirepressor.

PMID- 1384061
TI  - Oncogenic ras triggers the activation of 42-kDa mitogen-activated protein kinase
      in extracts of quiescent Xenopus oocytes.
AB  - Quiescent, full-grown Xenopus oocytes, which are arrested at the G2/M border of
      meiosis, contain an inactive 42-kDa mitogen-activated protein kinase (p42MAPK)
      that is activated when oocytes are stimulated to resume the meiotic cell cycle.
      We have made extracts from these oocytes that respond to four cell cycle
      activators: oncogenic [Val12]Ras protein, clam cyclins A delta 60 and B delta 97,
      and the phosphatase inhibitor okadaic acid. All four induce the tyrosine
      phosphorylation and activation of p42MAPK. Both cyclins and okadaic acid, but not
      [Val12]Ras, also lead to activation of the endogenous cyclin B/cdc2 kinase
      complexes in extracts of quiescent oocytes. Using extracts prepared from
      cycloheximide-arrested interphase cells, we show that although p42MAPK activation
      can occur in response to cyclin-activated cdc2, the Ras-induced activation of
      p42MAPK occurs without intervening cdc2 activation. Neither the nononcogenic
      [Gly12]Ras nor [Val12,Arg186]Ras, a mutant that lacks the C-terminal consensus
      sequence directing prenylation and subsequent membrane association, is an
      effective activator of p42MAPK in vitro.

PMID- 1384063
TI  - Kinetic role of nonnative species in the folding of bovine pancreatic trypsin
      inhibitor.
AB  - We have shown previously that during the oxidative folding of bovine pancreatic
      trypsin inhibitor only intermediates with native disulfide bonds are well
      populated. Nevertheless, these studies also confirmed the earlier conclusion
      [Creighton, T. E. (1977) J. Mol. Biol. 113, 275-293] that the rate-limiting
      transition in the kinetically preferred route for folding involves intramolecular
      disulfide bond rearrangements. Consequently, intermediates with nonnative
      disulfide bonds must form transiently during folding. Two specific nonnative
      species, denoted [30-51; 5-14] and [30-51; 5-38], in which numbers indicate
      residues participating in a disulfide bond, can be detected at low levels in
      kinetic folding experiments with bovine pancreatic trypsin inhibitor. By working
      with purified reversibly trapped intermediates, the role of these two nonnative
      species has been examined directly. These species are found to be in relatively
      rapid exchange with each other and with an initially formed native two-disulfide
      intermediate [30-51; 14-38]. Thus, the low abundance of the two nonnative species
      detected in kinetic folding experiments reflects primarily their low
      thermodynamic stability as compared to this native intermediate. To a small
      extent, these nonnative species form the productive native intermediate [30-51; 5
      55], which is the immediate precursor to the native protein. However, an equal
      amount of [5-55; 14-38], a nonproductive dead-end intermediate, is also produced.
      Thus, the nonnative species detected during the folding of bovine pancreatic
      trypsin inhibitor are not committed to forming the productive native
      intermediate, nor do they serve to direct folding specifically toward a
      productive route.

PMID- 1384065
TI  - Mouse mammary epithelium produces a soluble heat-sensitive macromolecule that
      inhibits differentiation of 3T3-L1 preadipocytes.
AB  - Coculture of normal mouse mammary gland (NMMG) epithelial cells with 3T3-L1
      preadipocytes resulted in inhibition of triglyceride accumulation. This
      inhibition was also observed when the NMMG cells were grown in inserts and placed
      within a 100-mm dish containing confluent 3T3-L1 cells. As the number of NMMG
      containing inserts was increased, there was a progressive decline in triglyceride
      content of the 3T3-L1 cells. Conditioned medium from NMMG cells also resulted in
      a dose-dependent inhibition of adipocyte formation, and when concentrated 10-fold
      by passage through a filter with a cutoff of 30 kDa, all of the inhibitory
      activity was recovered. Heating the concentrated conditioned medium at 98 degrees
      C for 30 min resulted in complete loss of activity. Of several peptides tested,
      transforming growth factor-beta, platelet-derived growth factor, tumor necrosis
      factor, interleukin 6, and basic fibroblast growth factor showed inhibitory
      activity, whereas epidermal growth factor, insulin-like growth factor I, and
      transforming growth factor-alpha did not.

PMID- 1384064
TI  - Roles of mechano-sensitive ion channels, cytoskeleton, and contractile activity
      in stretch-induced immediate-early gene expression and hypertrophy of cardiac
      myocytes.
AB  - Mechanical loading of cardiac and skeletal muscles in vivo and in vitro causes
      rapid activation of a number of immediate-early (IE) genes and hypertrophy of
      muscle cells. However, little is known as to how muscle cells sense mechanical
      load and transduce it into intracellular signals of gene regulation. We examined
      roles of putative cellular mechanotransducers, mechanosensitive ion channels, the
      cytoskeleton, and contractile activity in stretch-induced hypertrophy of cardiac
      myocytes grown on a deformable silicone sheet. Using the patch-clamp technique,
      we found a single class of stretch-activated cation channel that was completely
      blocked by gadolinium (Gd3+). Inhibition of this channel by Gd3+ did not affect
      either the stretch-induced expression of IE genes or the increase in protein
      synthesis. Neither disruption of microtubules with colchicine nor that of actin
      microfilaments by cytochalasin D prevented the stretch-induced IE gene expression
      and increase in protein synthesis. Arresting contractile activity of myocytes by
      high K+, tetrodotoxin, or Ba2+ did not affect the stretch-induced IE gene
      expression. Tetrodotoxin-arrested myocytes could increase protein synthesis in
      response to stretch. These results suggest that Gd(3+)-sensitive ion channels,
      microtubules, microfilaments, and contractile activity may not be necessary for
      transduction of mechanical stretch into the IE gene expression and hypertrophy.
      The stimulus of membrane stretch may be transmitted to the cell nucleus through
      some mechanisms other than electrical or direct mechanical transduction in
      cardiac myocytes.

PMID- 1384067
TI  - Potential antitumor agents XIX [1]. Synthesis and antitumor activity of tricyclic
      compounds related to lotifazole.
AB  - The synthesis of phenothiazine and anthraquinone derivatives, bearing at least
      one fragment present in lotifazole, is reported. Some of the new compounds showed
      antitumor activity in vitro (P388 leukemia cells) and in vivo (Ehrlich ascites
      tumor cells in mice).

PMID- 1384066
TI  - Orally administered interferons exert their white blood cell suppressive effects
      via a novel mechanism.
AB  - Interferons (IFN) have been approved for a number of clinical uses. The accepted
      routes of administration are intramuscular, subcutaneous, and intravenous.
      Recently, interferons administered by the oral route have been shown to exert a
      systemic effect. Oral administrations of IFN-alpha, IFN-beta, and IFN-gamma have
      been shown to cause a suppression of the peripheral white blood cell (WBC) count
      in mice. This study investigates the mechanism by which this suppression occurs.
      The results show that, in contrast to their intraperitoneal administration, oral
      administration of rHuIFN-alpha A/D or rMuIFN-gamma does not result in the
      presence of detectable levels of interferons in the blood. In addition, although
      the presence of circulating specific antibody to interferon blocks the peripheral
      WBC suppressive effects of intraperitoneally administered MuIFN-beta or rMuIFN
      gamma, the presence of those antibodies does not block the peripheral WBC
      suppressive effects of the orally administered interferons. The peripheral WBC
      suppressive effect of orally administered rHuIFN-alpha A/D and rMuIFN-gamma can
      be transferred by injection of blood from oral interferon-treated donor mice to
      recipient mice. Recipient mice receiving plasma from donor mice showed no
      peripheral WBC suppression. Recipient mice receiving blood cells from donor mice
      showed significant peripheral WBC suppression. No effect of orally administered
      rHuIFN-alpha A/D on the relative percentages of lymphocytes, neutrophils, and
      monocytes was noted. These results indicate that the mechanism by which orally
      administered interferons exert their WBC suppressive effect differs from that of
      intraperitoneally administered interferons. WBC suppression resulting from orally
      administered interferons may involve cell to cell transfer of the interferons'
      effects, rather than the systemic distribution of the interferons in the blood.
      These studies further suggest that there may be a role for oral administration as
      a new route of interferon administration and provide a glimpse into the mechanism
      by which the orally administered interferons exert their systemic effects.

PMID- 1384068
TI  - Altered systemic and tissue prostacyclin in cerulein induced acute pancreatitis
      in rats.
AB  - Prostacyclin metabolism in rat acute pancreatitis was evaluated by measuring the
      tissue levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and the
      urinary excretion of 2, 3-dinor 6-keto-PGF1 alpha. Acute pancreatitis was induced
      by i.v. cerulein perfusion and was confirmed by the pancreas enzyme changes and
      the histological findings. Significantly enhanced tissue and urinary prostacyclin
      levels were found in acute pancreatitis rats, when compared to the controls.
      Concomitantly, an enhanced tissue phospholipase A2 (PLA2) activity was also
      found. These data show the importance of 2, 3-dinor PGF1 alpha as an inflammatory
      marker in cerulein-induced pancreatitis.

PMID- 1384069
TI  - Evaluation of a prostacyclin analog in prevention of pulmonary oxygen toxicity.
AB  - Prolonged exposure to high concentrations of oxygen can result in significant
      lung injury, although newborn animals are tolerant relative to adults. We
      previously reported that relative O2 tolerance in the rabbit is lost by 10 days
      of age, and is coincident with a decline in lung prostacyclin. In the current
      study we administered iloprost, a stable prostacyclin analog, by continuous
      infusion to maturing rabbits exposed to greater than 95% oxygen. Compared to
      vehicle-treated controls, iloprost-treated rabbits had significantly lower
      protein in bronchoalveolar lavage fluid at 84 h, a smaller percentage of
      neutrophils at 65 and 84 h, and lower mortality at 96 h. The partial protection
      against pulmonary oxygen toxicity afforded by iloprost is likely due to its
      membrane stabilizing effect, and its inhibitory actions on neutrophil migration,
      activation, production of oxygen radicals and proteolytic enzymes.

PMID- 1384070
TI  - Behavioral and neurochemical changes in response to acute stressors: influence of
      previous chronic exposure to immobilization.
AB  - The effect of daily (2 h) exposure to immobilization (IMO) for 15 days on the
      behavioral and neurochemical responses of adult male rats to acute stress caused
      by 2-h IMO or 2-h tail-shock was studied. The brain areas studied were frontal
      cortex, hippocampus, hypothalamus, midbrain, and pons plus medulla. Chronic
      exposure to IMO did not alter noradrenaline (NA), 3-methoxy,4
      hydroxyphenyletileneglycol-SO4 (MHPG-SO4), serotonin, or 5-hydroxindoleacetic
      acid (5-HIAA) concentrations in any brain area as measured approximately 20 h
      after the last exposure to IMO. Exposure to behavioral tests did not modify
      neurochemical variables except NA levels in the hypothalamus of nonchronically
      stressed (control) rats. Both exposure to 2-h IMO or 2-h shock significantly
      decreased NA levels in hypothalamus and midbrain of nonchronically stressed rats.
      These decreases in response to the two acute stressors were not observed in
      chronically stressed rats. However, MHPG-SO4 levels increased to the same extent
      in control and chronically stressed rats after exposure to the acute stressors.
      Likewise, increased 5-HIAA concentrations observed in response to acute stressors
      were similar in control and chronically stressed rats. The inhibition of activity
      (areas crossed and rearing) in the holeboard caused by acute IMO was less marked
      in rats previously exposed to the same stressor than in control rats, but the
      response to shock was similar. In the forced swim test, acute IMO decreased
      struggling in control rats but tended to increase it in chronically stressed
      rats. The response to shock followed the same pattern as that to IMO, although it
      was slight.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384071
TI  - Dopaminergic and serotonergic function following isolation rearing in rats: study
      of behavioural responses and postmortem and in vivo neurochemistry.
AB  - This series of experiments compared isolation-reared and socially reared rats for
      their locomotor activity, behavioural stereotypy, and monoamine function both
      postmortem and in vivo using intracerebral dialysis. In Experiment 1, isolates
      showed an altered time course of locomotor activity following d-amphetamine
      sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC). Isolation
      reared rats also showed increased sensitivity to the sedative effects of a low
      dose of apomorphine hydrochloride (0.1 mg/kg) but did not differ from social
      controls following higher doses of the drug (0.5, 1.5, or 3.0 mg/kg, SC).
      Isolates showed a decrease in the intensity of apomorphine-induced stereotyped
      behaviours but no change in stereotypy induced by AMPH. In Experiment 2, isolates
      had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA
      function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens
      (NAC) or caudate putamen (CPu). Isolated rats also had a lower 5
      hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC
      (but not in the PFC or CPu) compared to controls. Experiment 3 used intracerebral
      dialysis to examine monoamine function in vivo following isolation rearing.
      Isolates showed greater increases in extracellular DA and greater decreases in
      DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu. There were no
      apparent differences in the perfusate concentrations of either dopamine (DA),
      dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug
      administration. However, consistent with the results of Experiment 2, isolates
      had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from
      the CPu. Experiment 4 measured postsynaptic DA function in CPu tissue slices
      following isolation. Isolation rearing did not affect cAMP accumulation in
      response to stimulation of D1 DA receptors by DA (0, 2.7, 9, or 30 microM). In
      addition, isolation rearing did not affect the coupling between D1 and D2
      receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5
      tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction
      by 10 microM quinperole hydrochloride (LY 171555). These results are discussed in
      terms of the possible relationship between these neurochemical findings and the
      behavioural disturbances following isolation rearing of rats.

PMID- 1384072
TI  - Astringent-tasting compounds alter ion transport across isolated canine lingual
      epithelia.
AB  - The effects of acid and astringent compounds on ion transport across isolated
      canine lingual epithelia were measured in an Ussing chamber. Lowering the pH from
      7.4 to 3.2 decreases ion transport, as measured by the short-circuit current
      (Isc), when the dorsal surface of the tongue is bathed in 0.5 M NaCl and
      increases Isc when it is bathed in 0.05 M NaCl, tannic acid (0.1 M) inhibits Isc
      at both pH 3.2 and 7.4. At 0.05 M NaCl, pH 7.4 tannic acid also inhibits Isc.
      Thus, inhibition of Isc by tannic acid does not depend upon the pH, meaning that
      the reduction in transport arises from tannic acid. In the presence of NaCl (at
      both 0.05 and 0.5 M NaCl), 0.1 M AlK (SO4)2 or 0.1 M AlNH4(SO4)2 also inhibit
      Isc. For these salts, the decrease in Isc arises from the aluminum ion and not
      from K+, NH4+, or SO(4-)-. Other less astringent compounds (gallic and tartaric
      acids) had only slight effects on Isc. The main findings of this study are that
      both tannic acid and the aluminum salts inhibited ion transport, likely Na+
      influx, via amiloride-inhibitable channels in isolated lingual epithelia.
      Inhibition of such Na+ channels may contribute to astringent taste.

PMID- 1384073
TI  - Ethacrynic acid and sulphasalazine inhibit the generation of leukotriene C4 in
      rat stomachs: a possible gastric anti-ulcer mechanism in cold-restraint-stressed
      rats.
AB  - The role of gastric glandular mucosal leukotriene C4 in gastric ulceration,
      produced by restraint at 4 degrees C (stress) for 2 h in rats, was studied in
      relation to the ulcer-preventing effects of ethacrynic acid, sulphasalazine and
      its constituents (sulphapyridine and 5-aminosalicylic acid), AA-861 and ONO-1078.
      Stress itself significantly raised mucosal leukotriene C4 levels; pretreatment
      with ethacrynic acid, sulphasalazine, sulphapyridine or AA-861 antagonised these
      changes and reduced the severity of gastric ulceration. Mucosal mast cell
      degranulation was prevented by ethacrynic acid, sulphasalazine, 5-aminosalicylic
      acid, AA-861 or ONO-1078; the mucus-depleting effect of stress was also reversed
      by all these drugs, except for 5-aminosalicylic acid. The anti-ulcer effect of
      ethacrynic acid and sulphasalazine appears to be related to their influence on
      glandular mucosal leukotriene C4 levels.

PMID- 1384074
TI  - Central and peripheral motor effects of galanin on the duodenojejunum and colon
      in fed rats.
AB  - The effects of intraperitoneal, intrathecal and intracerebroventricular
      injections of the peptide galanin (GAL) on duodenojejunal and colonic motility
      were studied in conscious fed rats. At 0.3-3.0 nmol/rat, intraperitoneal GAL
      restored the 'fasted pattern' of duodenojejunal activity, i.e. the migrating myo
      electric complex (MMC) was restored for a short period of time, and the MMC
      frequency was not significantly different from that observed before feeding. In
      addition, the activity of the proximal but not of the distal colon was
      significantly increased by GAL administration. The intracerebroventricular
      administration of GAL (0.03-0.3 nmol/rat) induced an MMC fasted pattern on the
      duodenojejunum after a latency period of about 1 h. In these experiments proximal
      colonic motor activity was significantly increased for 120-180 min. GAL given
      intrathecally (0.03-0.3 nmol/rat) induced a long-lasting fasted pattern of the
      intestinal activity within 10-20 min which was not dose dependent in duration,
      while the motility index of the proximal colon was significantly increased.
      Pretreatment with naloxone prevented the specific effects of GAL, given
      intracerebroventricularly or intrathecally, on the duodenojejunum and colon and
      the colonic response, but not the restoration of the MMC pattern on the
      duodenojejunum, induced by GAL given intraperitoneally. Ketoprofen pretreatment
      was completely ineffective. These observations indicate a plurality of sites of
      action of GAL on digestive tract motility including local duodenal receptors and
      suggest the importance of a spinal component in the control of motility by GAL
      when given intrathecally. Moreover the present results indicate the involvement
      of opioid receptors in the fasted pattern induced by GAL given
      intracerebroventricularly or intrathecally and in the colonic effects regardless
      of the route of administration.

PMID- 1384075
TI  - Risperidone in the treatment of disorders with a combined psychotic and
      depressive syndrome--a functional approach.
AB  - In vitro receptor-binding profiles and in vivo pharmacological studies have shown
      risperidone to be a potent mixed serotonin-S2 dopamine-D2-like receptor
      antagonist. While anti-D2 activity may relate to the antipsychotic potency of
      neuroleptic drugs, an antidepressive efficacy of substances with anti-S2 activity
      has been suggested. In an open pilot-study, ten patients with schizodepressive
      disorders or a DSM-III-R diagnosis of psychotic major depressive episodes were
      treated with risperidone (2-10 mg/d) for six weeks. Weekly psychopathological
      evaluation was performed, including BPRS, SANS, SAPS, VAS scales, and AIMS and
      UKU for the assessment of side-effects. Generally, the psychotic syndrome (BPRS,
      SANS and SAPS) decreased markedly in all patients; seven patients also showed a
      clinically significant improvement of depressive symptoms (BPRS). Except for two
      patients who needed biperiden because of extrapyramidal side-effects, the
      tolerance of risperidone was good. The antipsychotic and antidepressive
      properties of risperidone shown in our pilot study are promising enough to merit
      full double-blind controlled trials for further evaluation of its therapeutic
      value in this broad spectrum of psychiatric disorders.

PMID- 1384077
TI  - Prostate cancer screening.
AB  - No screening test has been proven to reduce prostate cancer mortality. DRE has
      been the traditional method of screening, and it is often used to detect other
      diseases in addition to prostate cancer. Newer modalities, such as TRUS and PSA,
      can identify patients with nonpalpable prostate cancer, but the use of these
      tests will also result in many false-positives. In addition, it is not known
      whether the use of these tests will reduce prostate cancer mortality, or instead
      cause harm to those patients screened. Given the potential for harm, and the
      extraordinary expense, routine screening of asymptomatic men with newer
      modalities should be considered experimental.

PMID- 1384076
TI  - Influence of early undernutrition in rats on their body fat and RNA content in
      VMH neurons.
AB  - The RNA content of the ventromedial hypothalamus (VMH) and lateral hypothalamic
      area (LHA) neurons, and the epididymal, retroperitoneal, and liver fat content of
      150-day-old male rats submitted to neonatal undernutrition, were investigated.
      The neonatal undernutrition was carried out by two different ways. First, by
      reducing the litters to two pups per nest from birth to weaning. The pups from
      normal litters (eight pups/nest) served as controls. Secondly, by separating half
      of the pups (four pups) from normal litters for 8 h daily during the first 5
      postnatal days. The remaining nonseparated pups served as their controls. The
      data show that both groups of early undernourished pups had a significantly
      increased RNA content in the VMH neurons (RNA content in the LHA neurons was
      unchanged) and a significantly decreased epididymal, retroperitoneal, and liver
      fat content in comparison with their controls. The results indicate that early
      undernutrition leads to a permanent increase in the functional activity of VMH
      and alteration in fat metabolism in rats.

PMID- 1384078
TI  - Conditioned tolerance in human opiate addicts.
AB  - Repeated administration of opioid drugs results in tolerance, a lessening of the
      drug's effect. There is pre-clinical evidence suggesting a conditioning component
      to drug tolerance. In the present study, six former opiate dependent subjects
      received i.v. opiate either by un-signalled infusion or by signalled self
      injection and the effects were compared with those of saline under double-blind
      conditions. The subjects' pre-injection rituals constitute a signal which
      reliably predict the appearance of the opiate. These rituals produced drug
      opposite physiological responses which resulted in an attenuation of the effects
      of the drug. Thus, tolerance was observed when the subjects injected the opiate,
      but not when the same dose was received by un-signaled intravenous infusion.
      These results are consistent with a conditioning explanation for the observed
      drug tolerance.

PMID- 1384079
TI  - Effect of ACTH, adrenalectomy and the combination treatment on the density of 5
      HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor
      mediated wet-dog shake behaviors.
AB  - The effect of ACTH and/or adrenalectomy on serotonin (5-HT)2 receptor binding
      sites was evaluated in the neocortex of rat forebrain. One day after the
      adrenalectomy or sham operation, ACTH (50 micrograms/day) was injected
      subcutaneously into adult male SD rats for 10 consecutive days. Saturation
      analysis showed that subchronic ACTH treatment significantly increased the Bmax
      values for 3H-ketanserin binding without any change in the Kd values. Moreover,
      this ACTH-induced increase in the Bmax values was prevented by adrenalectomy. The
      concentrations of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) measured by HPLC
      ECD were not altered by these manipulations. Ten-day administration of
      corticosterone (20 and 50 mg/kg) also increased 5-HT2 receptor density in the
      neocortex of rat forebrain. 5-HT2 (and 5-HT1C) receptor agonist, (+/-)DOI-induced
      wet-dog shakes in ACTH and/or adrenalectomy-treated rats were also examined. Ten
      day administration of ACTH enhanced (+/-)DOI-induced wet-dog shakes and this
      increase was prevented by adrenalectomy. These results indicate that subchronic
      adrenocorticotropin-adrenal axis activation of rats increases both the number of
      5-HT2 receptors in neocortex of forebrain and the wet-dog shake responses induced
      by (+/-)DOI.

PMID- 1384080
TI  - Transfection of the Escherichia coli nth gene into radiosensitive Chinese hamster
      cells: effects on sensitivity to radiation, hydrogen peroxide, and bleomycin
      sulfate.
AB  - The Escherichia coli nth gene encodes endonuclease III, which catalyses the
      glycolytic removal of various oxidized thymine residues from DNA. A truncated
      version of nth, with the prokaryotic regulatory sequences removed, was ligated
      into the retrovirus-based vector pZipneoSV(X)1 and transfected into the
      radiosensitive Chinese hamster ovary cell line, xrs7. Following selection with
      G418, two clones (x7nth1 and x7nth6) were shown by Southern analysis to contain
      the nth gene. No substantial difference in gamma-ray sensitivity was detected
      between xrs7, clones x7nth1 and x7nth6, and the parent vector transfected clone
      (x7neo1). However, clones containing the nth gene were more resistant to hydrogen
      peroxide cytotoxicity [D0's for x7nth1 and x7nth6 were 0.072 microgram/ml (4
      microM) and 0.046 microgram/ml, respectively, compared with D0's of 0.034 and
      0.027 microgram/ml for xrs7 and x7neo1, respectively] but markedly more sensitive
      to bleomycin sulfate cytotoxicity than xrs7 and x7neo1 (e.g., 1D0's for x7nth6
      and xrs7 were 0.05 and 0.12 microgram/ml, while 2D0's for x7nth1 and xrs7 were
      0.35 and 0.48 microgram/ml, respectively). Alterations in sensitivity to hydrogen
      peroxide and bleomycin sulfate could not be explained by differences in the
      distribution of the cell-cycle phases and growth rate of nth-containing clones
      and control cell lines. These results are consistent with the hypothesis that
      modified thymine lesions are potentially cytotoxic. Hence, when cells incur a
      high level of endonuclease III-repairable damage relative to strand breakage,
      such as after treatment with hydrogen peroxide, increased repair capacity
      increases survival. Gamma radiation produces a lower level of endonuclease III
      repairable damage relative to all the other types of lesions produced; hence
      increased repair capacity has no measurable effect on cell survival. The
      increased sensitivity of x7nth1 and x7nth6 to bleomycin sulfate toxicity may
      indicate that, when thymine damage and single-strand breaks are in close
      proximity on opposite strands of the DNA, endonuclease III, which incises DNA at
      the site of damaged residues, can increase the number of double-strand breaks and
      hence decrease the level of cell survival.

PMID- 1384081
TI  - Transrectal US in evaluation of patients after radical prostatectomy. Part II.
      Transrectal US and biopsy findings in the presence of residual and early
      recurrent prostatic cancer.
AB  - The anatomic appearance of the prostatic fossa on transrectal ultrasound (TRUS)
      scans obtained after radical retropubic prostatectomy (RRP) for carcinoma was
      studied in 16 patients in whom local recurrence was suspected on the basis of
      rising serum prostate-specific antigen (PSA) levels above 0.4 ng/mL, negative
      pelvic computed tomographic scans, and negative bone scans. Findings in samples
      obtained with ultrasound (US)-guided biopsy were compared with those in samples
      obtained with digitally guided biopsy (DGB); each patient was his own control.
      When the postoperative anatomic appearance on TRUS scans was compared with that
      in patients without suspected recurrence of cancer, no significant difference was
      seen. Needle biopsy was positive for carcinoma in eight patients (50%): US-guided
      biopsy, in seven patients; DGB, in five patients; and both US-guided biopsy and
      DGB, in four patients. US-guided biopsy has limited usefulness over DGB in
      patients with rising PSA levels after RRP, but use of both DGB and US-guided
      biopsy may maximize sensitivity. The main value of TRUS may be in accurate
      positioning of the biopsy needle about the vesicourethral anastomosis.

PMID- 1384082
TI  - Release of endogenous neurochemicals may increase vascular permeability, induce
      edema and influence cell changes in trauma to the spinal cord.
AB  - Trauma to the spinal cord induces a series of electrophysiological, immunological
      and biochemical events, but it is still unclear how such reactions are initiated
      and maintained. Most likely release of neurochemicals, breakdown of microvascular
      permeability and the formation of vasogenic edema play important roles in the
      pathophysiology of spinal cord trauma. In an animal model we have focused the
      attention to the possible involvement of endogenous serotonin, prostaglandins and
      opioid peptides in the formation of edema and associated disturbances of vascular
      permeability. The trauma was produced in anesthetized rats by making a focal
      lesion in the right dorsal horn at the T10-11 segments. This injury resulted in a
      profound increase in the microvascular permeability to 131I-sodium and an
      elevation of water content in the rostral T9 and caudal T12 segments as measured
      5 h after the onset of the injury. Light microscopy of the perifocal changes in
      the T9-T12 segments using Nissl stain and immunohistochemistry to glial
      fibrillary acidic protein (GFAP) and myelin basic protein (MBP) showed profound
      cellular changes which were most severe in the ipsilateral ventral horn. Many
      nerve cell bodies were shrunken and the tissue had a spongy edematous appearance.
      There was a marked increase of GFAP immunoreactivity as well as a significant
      diminution of MBP staining. Pre-treatment with p-chlorophenylalanine (p-CPA, an
      endogenous serotonin depletor and synthesis inhibitor) or indomethacin (an
      endogenous prostaglandin synthesis inhibitor) or naloxone (an opioid receptor
      antagonist) significantly reduced the permeability changes and the edema
      formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384083
TI  - Non-vasopressinergic, non-oxytocinergic neuropeptides in the rat hypothalamo
      neurohypophyseal tract: experimental immunohistochemical studies.
AB  - The hypothalamo-neurohypophyseal tract is known to contain the classical
      neurohypophyseal hormones vasopressin and oxytocin. Additionally, dynorphin,
      methionine- and leucine-enkephalin, cholecystokinin (CCK), corticotropin
      releasing factor (CRF), and galanin are co-stored with vasopressin and/or
      oxytocin. Recent immunohistochemical studies have revealed the existence of a low
      to moderate number of substance P-, vasoactive intestinal peptide (VIP)-,
      neuropeptide Y (NPY)- and somatostatin-immunoreactive nerve fibers within the rat
      neurohypophysis. VIP-, substance P- and NPY-immunoreactive fibers were
      distributed throughout the organ, whereas somatostatin-immunoreactive fibers were
      present in the proximal part of the organ. The positive nerve endings were either
      large in size resembling classical nerve terminals related to perivascular
      spaces, or smaller similar to peptidergic fibers as described in the CNS. These
      results indicate that these neuropeptides may be either co-stored with the
      classical neurohypophyseal hormones or contained in another system of afferents
      to the organ. The probably distinct functional roles of these neuropeptides in
      the physiology of the neurohypophysis are discussed.

PMID- 1384085
TI  - Aspects of normal cerebrospinal fluid circulation and circumventricular organs.

PMID- 1384084
TI  - Role of the OVLT in the febrile response to circulating pyrogens.
AB  - The available data suggest that circulating endogenous pyrogens (EPs) probably do
      not penetrate the brain, but interact with sensory elements in the organum
      vasculosum laminae terminalis (OVLT) which may involve 5HT and SP as
      neurotransmitters. It is proposed that substance P (SP) may affect thermo
      regulatory neurons in the preoptic area (POA) directly or induce the local
      synthesis of cytokines that secondarily act on these neurons. Recent evidence
      indicates that endothelial cells in the OVLT bind circulating cytokines to
      receptors on their luminal surface. This may result in the release of putative
      neuroregulators which then process the original signals inwardly to the POA,
      where they then affect neuronal functions leading to fever production. Thus,
      trans-BBB passage of cytokines is prevented, but the brain site mediating their
      pyrogenic effect is informed and the appropriate responses are activated. It is
      emphasized, however, that this suggested mechanism is still speculative.

PMID- 1384086
TI  - [Glycoconjugate receptors for microorganisms].

PMID- 1384087
TI  - [Carbohydrate antigens expressed on the insect neuronal cells].

PMID- 1384088
TI  - [Lectin staining of tissues and cells].

PMID- 1384090
TI  - International symposium on substance P and related peptides. Pain, inflammation,
      visceral and CNS functions. November 3-6, 1992, Shizuoka, Japan. Abstracts.

PMID- 1384089
TI  - The role of radiotherapy in the treatment of primary mediastinal seminoma.
AB  - Nine patients with primary mediastinal seminoma were treated with radiotherapy.
      All patients achieved complete response on chest radiography. None of the three
      patients treated with whole mediastinal irradiation relapsed. Four of the six
      patients with involved-field irradiation had marginal relapses, suggesting the
      efficacy of the whole mediastinal irradiation.

PMID- 1384091
TI  - Diurnal variation of amylase secretion is coupled with alterations of beta
      adrenoceptors in the rat parotid gland.
AB  - Diurnal changes in the neurotransmitter receptors are important for studying the
      receptor function in neurophysiology. The purpose of this study is to gain an
      insight into the regulatory mechanisms of the diurnal variation of amylase
      secretion. Rat salivary amylase levels showed a diurnal variation with two peaks,
      a marked peak at 13 h and a lesser peak at 21 h. This increase in salivary
      amylase levels was completely inhibited by pretreatment of rats with the beta
      adrenergic antagonist propranolol, but not by the alpha-adrenergic antagonist
      phentolamine. Amylase level in parotid tissue homogenate also showed a diurnal
      change, but there was only one peak, at 13 h. The number of maximal binding sites
      (Bmax) for [3H]dihydroalprenolol (DHA) in parotid membranes showed a diurnal
      variation with two marked peaks at 13 and 21 h, but the affinity of parotid beta
      adrenoceptors for agonists or antagonists did not show any diurnal changes.
      Phosphorylation of nuclear non-histone proteins in the rat parotid gland showed
      diurnal variation with two marked peaks at 13 and 21 h. These results indicate
      that a diurnal variation in the number of rat parotid beta-adrenoceptors, which
      is presumably regulated by gene expression, is coupled with a change in salivary
      amylase secretion.

PMID- 1384092
TI  - Detection of the granulocyte colony-stimulating factor receptor using
      biotinylated granulocyte colony-stimulating factor: presence of granulocyte
      colony-stimulating factor receptor on CD34-positive hematopoietic progenitor
      cells.
AB  - Granulocyte colony-stimulating factor (G-CSF) was linked to NHS-biotin to yield
      biotinylated G-CSF (b-G-CSF), which retained the ability to stimulate colony
      formation by normal bone marrow (BM) cells in methylcellulose. The use of
      streptavidin-phycoerythrin conjugate in conjunction with flow cytometry
      demonstrated that the binding of biotinylated G-CSF to its receptor is saturable,
      competitive, and specific. A 100-fold molar excess of unlabeled G-CSF almost
      completely inhibited the binding of the biotinylated G-CSF to the human leukemia
      cell line U937, which is known to possess the G-CSF receptor. G-CSF receptors
      were clearly detected by flow cytometry on adult human peripheral granulocytes
      and monocytes, but not on lymphocytes. Using this method, the expression of G-CSF
      receptors on hematopoietic progenitor cells in bone marrow and umbilical cord
      blood, detected as CD34-positive (CD34+) cells, were examined. A small but
      significant number of CD34+ cells were detected among the bone marrow mononuclear
      cells and umbilical-cord-blood mononuclear cells (4.28% +/- 0.31%, 1.09% +/-
      0.20%, respectively). The percentage of CD34+ BM mononuclear cells was
      significantly higher than for cord blood mononuclear cells (P less than 0.01).
      These CD34+ cells were then analyzed by biotinylated G-CSF binding. CD34+ cells
      from bone marrow contained 25.8% +/- 7.9% G-CSF receptor positive cells and those
      from cord blood possessed 29.2% +/- 7.0% of G-CSF receptor-positive cells. The
      difference was not statistically significant.

PMID- 1384093
TI  - Replication of human immunodeficiency virus in HL-60 cells.
AB  - HL-60 cells carrying the CD4 marker could be productively infected with human
      immunodeficiency virus (HIV) but did not form syncytia, though 11-14 days p.i.,
      there was a transient decrease in cell multiplication and viability. After
      prolonged passage, a subpopulation of HL-60 cells was selected. The virus
      produced differed from the initial input virus grown on CEM cells: the virions
      lacked knobs, were either empty or had abnormal cores, had a higher ratio
      p24/gp41,gp110 and were less infectious. After prolonged passage, virus was
      produced which was fully infectious for CEM but not for fresh HL-60 cells, and
      which ressembled the input virus with respect to morphology and p24/gp41,gp110
      ratio.

PMID- 1384094
TI  - Digital indocyanine green videoangiography and choroidal neovascularization.
AB  - This report describes a new system for digital indocyanine green videoangiography
      (ICGV) that provides enhanced imaging of the choroidal circulation. This newly
      assembled system was used to study a consecutive series of 129 patients with
      exudative age-related macular degeneration (AMD), and ill-defined or occult
      choroidal neovascularization (CNV). Overall, 39% of the patients in this study
      with occult CNV could be reclassified as having well-delineated or so-called
      classic CNV by virtue of the additional findings provided by ICGV. In this
      series, ICGV was particularly useful in identifying occult CNV in eyes with a
      large, serous pigment epithelial detachment (PED) and in eyes with recurrent CNV
      after previous laser photocoagulation treatment. Some of these patients were
      selected for laser photocoagulation of the abnormal choroidal vessels in order to
      evaluate the feasibility of this form of treatment on the basis of combined
      clinical, fluorescein angiographic, and ICGV findings. The results of this study
      suggest that ICGV is an important adjunct in the evaluation, classification, and
      laser treatment of patients with occult CNV secondary to AMD.

PMID- 1384095
TI  - Vitreoretinal techniques in the treatment of choroidal neovascular membranes.

PMID- 1384096
TI  - Immunopharmacology of new xenobiotic immunosuppressive molecules.

PMID- 1384098
TI  - [Physiology of enterochromaffin-like cells in the regulation of gastric acid
      secretion].

PMID- 1384097
TI  - Special issues in pediatric renal transplantation.

PMID- 1384099
TI  - [Interferons].
AB  - The interferons are a family of proteins that are grouped together on the basis
      of their antiviral, antiproliferative and immunomodulatory effects. They are
      divided into three classes: alpha, beta, and gamma, which can be distinguished
      structurally, biochemically, and antigenically. Clinically they are used for the
      treatment of malignant tumors and of viral diseases, particularly of chronic
      viral hepatitis. The present role of interferons as therapeutic agents in the
      treatment of viral hepatitis will be critically discussed in the lecture.

PMID- 1384100
TI  - Prostatic hyperplasia over 80 grams weight, is transurethral resection an
      adequate procedure? Results of a prospective study.
AB  - A prospective study of transurethral resection with continuous low pressure
      irrigation was undertaken to find out, whether large prostates can be operated
      transurethrally without undue risk. Since 1986, the beginning of the study, 121
      prostates with adenomas over 80 grams weight (> 80 g group) were resected. The
      mean age of the patients was 70.1 years, the mean weight of the resected prostate
      tissue was 104 grams in 66 minutes. The postoperative mortality was below 1% (1
      patient). 17 patients (14%) needed blood transfusion, 11 patients had
      peroperative hemodilution. Even with large prostate, considering the rather high
      mean age of the patients treated, there is no considerably elevated operating
      risk, when large prostates are resected transurethrally. It however has to be
      emphasized, that this is achieved only with continuous low pressure irrigation
      and the loop of a 28 Fr. standard resectoscope in combination with an
      automatically regulated electrosurgical unit.

PMID- 1384101
TI  - [Role of platelet activating factor and its antagonists in bronchial asthma].
AB  - Inhalation of the platelet activating factor (PAF) produces symptoms of bronchial
      asthma, a disease in which PAF plays an important role. This lipid mediator
      released by many kinds of cells exerts its effects on blood cells and on cells of
      the bronchial wall both directly and indirectly. The crucial role played by PAF
      in the inflammatory cascades explains the current interest in specific PAF
      antagonists. These antagonists have both bronchodilator and anti-inflammatory
      properties and act simultaneously as beta-adrenoceptor agonists and
      corticosteroids. The first clinical trials of PAF antagonists in the treatment of
      resistant asthma have given results that are interesting but not superior to
      those obtained with the conventional anti-asthmatic drugs. The indications for
      PAF antagonists combined with other specific antagonists will soon be determined.

PMID- 1384104
TI  - Naturally occurring renal neurofibroma in a laboratory beagle.

PMID- 1384103
TI  - Plasma interleukin-6 and renin substrate in reactive arthritis, rheumatoid
      arthritis, and systemic lupus erythematosus.
AB  - In order to study the role of interleukin-6 (IL-6) in inflammatory disease we
      monitored plasma levels of IL-6 and acute phase proteins such as C-reactive
      protein (CRP) and renin substrate (RS) in patients with reactive arthritis (ReA),
      rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Venous plasma
      samples were collected: (1) during the acute phase or exacerbation of the
      disease, and (2) several months latter during convalescence. Increased mean [95%
      confidence intervals (CI)] levels of plasma IL-6 were observed in patients with
      ReA both in the acute phase and later, 229 (177 to 280) ng/l and 197 (134 to 260)
      ng/l respectively (P less than 0.001 as compared to controls). The corresponding
      plasma IL-6 levels in RA patients were 283 (223 to 340) ng/l and 183 (151 to 226)
      ng/l, respectively (P less than 0.001 as compared to controls). Plasma IL-6
      levels in SLE patients were not increased. Plasma RS levels were increased in all
      patient groups, but no significant correlation to IL-6 or CRP levels was
      observed, whereas plasma IL-6 and CRP levels showed a positive correlation in ReA
      and RA patients.

PMID- 1384102
TI  - Epitope specificity of antibodies to type II collagen in rheumatoid arthritis and
      systemic lupus erythematosus.
AB  - Antibodies to human type II collagen were examined in the sera of 105 patients
      with rheumatoid arthritis (RA), 44 patients with systemic lupus erythematosus
      (SLE) and 11 patients who fulfilled the criteria of both diseases (RA-SLE
      overlap), using a solid-phase radioimmunoassay (RIA). The frequencies of
      antibodies to native and denatured human type II collagen were 20% and 27% in RA,
      14% and 16% in SLE, and 45% and 36% in RA-SLE overlap. The specificity of the
      antibodies was further examined by inhibition with native and denatured type II
      collagen, by immunoblotting on native and denatured type II collagen, and by
      immunoblotting on cyanogen-bromide derived polypeptides of type II collagen. We
      could not identify any disease-specific patterns of reactivity. Thus, in the
      three disease groups the antibody response was polyclonal; there were antibody
      populations that reacted with native and/or denatured collagen, and epitopes
      could be assigned to at least three CB peptides, CB10.5, CB11 and CB8.

PMID- 1384105
TI  - Granular basal cell tumor in a Wistar rat.
AB  - A granular cell variant of a cutaneous basal cell tumor in a Wistar rat is
      described. The tumor resembles the variant as described in man and dogs. The
      granular basal cells contain cytoplasmic PAS positive granules, and immunostained
      positively with HMW cytokeratins. Ultrastructurally, the cytoplasmic granules
      were secondary lysosomes.

PMID- 1384106
TI  - Ovarian carcinomas express a sperm acrosomal antigen, defined by monoclonal
      antibody 9H8.
AB  - A new monoclonal antibody (MAb 9H8, IgM class) reactive with human ovarian
      carcinoma has been raised after immunizing C57BL/6 mice with bovine sperm.
      Immunohistological studies indicated that 20/21 serous ovarian adenocarcinomas
      expressed 9H8-defined antigen but it was absent in benign ovarian tumors (0/11).
      1/11 of breast carcinomas and 5/5 of rectal carcinomas expressed this antigen,
      although to a considerably lesser degree. Tumors of lung, skin, brain and
      mesothelium were negative. The antigen was also expressed in embryonic skin, in
      renal collecting tubule cells and in saliva. In bovine, human and mouse sperm the
      antigen is confined to the acrosomal region. The molecular weight of this antigen
      was determined by Western blot analysis and gel filtration. In SDS-PAGE the
      antigen ran as a broad band barely entering the 7% gel, indicating an apparent
      molecular weight > 300 kDa. In the absence of detergents and reducing agents this
      glycoprotein forms larger complexes (> 1,500 kDa) as determined by gel filtration
      on Sephacryl S300. The epitope contains carbohydrate structures recognized by
      lectin PNA (peanut agglutinin).

PMID- 1384107
TI  - Gene dosage and down-regulation of the alpha-interferon receptor.
AB  - The gene coding for the alpha,beta-interferon (alpha,beta-IFN) receptor is
      localized to chromosome 21. Cells from patients with Down's syndrome (trisomy 21)
      contain an extra chromosome 21, which results in a 1.5 times increase of dosage
      for the genes localized to this chromosome. Trisomy 21 cells express more cell
      surface alpha-IFN receptors, consistent with the increased gene dosage. Down
      regulation of the alpha-IFN receptors in trisomy 21 and normal cells was studied
      by incubating the cells with alpha-IFN. The alpha-IFN-induced effects showed 1.6
      times more internalized cell-surface alpha-IFN receptors in trisomy 21 cells
      compared with normal cells, but no statistically significant change in the
      dissociation constants. A close relationship was found between the alpha-IFN
      receptor number and the biological response expressed as 2',5'-oligoadenylate
      synthetase activity.

PMID- 1384108
TI  - Effect of short-termed pancreatic duct obstruction on the pancreatic subcellular
      organellar fragility and pancreatic lysosomal enzyme secretion in rabbits.
AB  - We studied the effect of short-term (3 h) pancreatic duct obstruction (PDO) on
      the exocrine pancreas and on the secretion of lysosomal enzymes into the
      pancreatic juice of rabbits during stimulation by pancreatic secretagogues. The
      following evaluations were made: serum amylase levels, pancreatic water content,
      pancreatic amylase, trypsinogen and cathepsin B content, and output of pancreatic
      enzymes and lysosomal hydrolases when stimulated by secretin and caerulein as
      well as the distribution of cathepsin B in subcellular fraction. Cellular
      fragility (LDH leakage from dispersed acini) and subcellular organellar fragility
      (cathepsin B leakage from lysosomes and malate dehydrogenase leakage from
      mitochondria) were also evaluated. PDO for 3 h plus secretin infusion caused a
      significant rise in serum amylase levels, pancreatic water content, and
      pancreatic amylase and trypsinogen content due to congestion of digestive enzymes
      during PDO. There was also a redistribution of cathepsin B from the lysosomal
      fraction to the zymogen fraction and increased cellular and subcellular
      organellar fragility. In normal rabbits and in those with only secretin infusion,
      caerulein stimulated the secretion of cathepsin B into pancreatic juice. Just
      after PDO, the secretion of cathepsin B, amylase and trypsinogen significantly
      decreased. By 24 h after PDO, the output of cathepsin B stimulated by caerulein
      and secretin had increased significantly. Amylase and trypsinogen output were
      also significantly increased at this stage, in both the secretin and caerulein
      fractions. These results indicate that the secretion of lysosomal enzymes into
      pancreatic juice is stimulated by gut hormones, such as caerulein, in the normal
      physiological state and in pathological states, such as PDO. These results also
      show an important role of increased cellular and subcellular organellar fragility
      in the pathogenesis of pancreatic injuries induced by PDO and augmented secretion
      of both lysosomal enzymes and pancreatic digestive enzymes in the recovery stage
      after PDO and their important roles at this stage. Lysosome enzymes also seem to
      play some physiological roles in the pancreatic ductal system in normal
      physiological states as well as their roles in pathological states, because
      cathepsin B can activate trypsinogen, and trypsin can activate many other
      enzymes.

PMID- 1384109
TI  - Immunolocalization of beta 1 integrins in human gingival epithelium and cultured
      keratinocytes.
AB  - Beta 1 integrins are cell surface receptors for extracellular matrix binding. We
      have recently shown that these receptors may also play a role in cell-cell
      binding of human epidermal keratinocytes. In this study we used
      immunofluorescence and confocal laser scanning microscopy to localize beta 1
      integrins in frozen sections of human gingiva and cultures of human gingival
      keratinocytes. The results show that beta 1 integrin polypeptides, localized by
      monoclonal and polyclonal antibodies, were detected mainly in the basal layer of
      the keratinized epithelium. There was also scattered staining in connective
      tissue fibroblasts, nerves, and blood vessel walls. In the basal layer, the
      integrins were found around the entire periphery of the basal keratinocytes.
      Furthermore, confocal laser scanning microscopy (CLSM) revealed that most of the
      staining was in fact localized in dot-like structures at the lateral cell
      membranes of neighboring basal cells. In cultured human gingival keratinocytes
      maintained in low calcium (0.15 mM) conditions beta 1 integrins were localized in
      several different structures: trails which were left behind when the cells moved
      in culture, dots underneath the cells, around the nucleus, and in cell-cell
      contacts. The trails were also found to contain fibronectin and type IV collagen
      but not laminin. Switching the keratinocytes to high calcium (1.2 mM) conditions
      induced the formation of cell-cell contacts which were strongly positive for beta
      1 integrins. No fibronectin or type IV collagen was found in cell-cell contact
      sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384110
TI  - Hepatitis B core antigen-specific interferon gamma production of peripheral blood
      mononuclear cells during acute exacerbation of chronic hepatitis B.
AB  - To examine the relationship between hepatitis B core antigen-specific interferon
      gamma production and the liver injury, we measured the sequential change in this
      production by peripheral blood mononuclear cells of seven patients with chronic
      hepatitis B. Four patients who experienced acute exacerbation showed increased
      interferon gamma production when the serum alanine aminotransferase level peaked
      or during the recovery phase. In the three patients who did not experience acute
      exacerbation, interferon gamma production gradually decreased in one who had a
      low peak of alanine aminotransferase but did not show significant change in the
      other two. Increased production of hepatitis B core antigen-specific interferon
      gamma at the time of acute exacerbation suggests that interferon gamma induced by
      hepatitis B core antigen plays a role in hepatocellular injury of patients with
      chronic hepatitis B.

PMID- 1384111
TI  - Effect of ethanol intake on pancreatic exocrine secretion in mice.
AB  - Swiss mice were fed conventional lab chow and 10% ethanol or water as drinking
      fluid for 2 weeks. Pancreatic juice was obtained by cannulation of the bile
      pancreatic common duct of mice anesthetized with urethane. Isolated pancreatic
      lobules were also obtained. The flow rate and the amylase output were determined
      in pure pancreatic juice. The release of amylase was measured in pancreatic
      lobule preparations. The basal pancreatic juice flow rate and the amylase output
      were significantly increased by ethanol consumption. The magnitude of the
      pancreatic juice flow rate and the amylase output responses to increasing doses
      of bethanechol, a cholinergic agent, was significantly decreased in ethanol-fed
      mice. The amount of spontaneously released amylase was higher in pancreatic
      lobule preparations from ethanol-fed animals than that from control mice, and the
      difference was abolished by addition of atropine to the incubation media. The
      amylase release rate in response to increasing doses of bethanechol was
      significantly reduced in lobule preparations from the ethanol-fed group. These
      data indicate that ethanol intake in mice has a stimulating effect on the
      spontaneous pancreatic secretion and lends support to the hypothesis that ethanol
      consumption increases the intrapancreatic cholinergic tone.

PMID- 1384112
TI  - Persistence of viremia in patients with type-C chronic hepatitis during long-term
      follow-up.
AB  - To clarify the evolution of antibody to hepatitis C virus (anti-HCV) and of liver
      histologic findings during the natural course of type-C chronic hepatitis, 111
      patients with biopsy-proven chronic hepatitis type C were consecutively enrolled
      in this study and were followed up biochemically, serologically, and
      histologically for more than 5 years. All were positive for the first- and second
      generation antibody to HCV (anti-HCV-1 and anti-HCV-2). None received antiviral
      therapy during the follow-up period. At the end of follow-up, all remained
      positive for anti-HCV-2, but four patients turned negative for anti-HCV-1. HCV
      RNA, detected by the polymerase chain reaction method, was tested serially in 20
      patients who persisted positive anti-HCV-1 and in 4 patients who lost anti-HCV-1.
      HCV RNA disappeared from only two patients, who lost anti-HCV-1 during the follow
      up period. A normalization of the serum transaminase level was found in only two
      patients, who lost both anti-HCV-1 and HCV RNA. A repeat liver biopsy was
      performed in 62 patients with chronic hepatitis who were persistently positive
      for all HCV markers and in 4 patients who lost anti-HCV-1. Of the 62 patients who
      retained all HCV markers, 16 progressed to hepatocellular carcinoma, 6 to
      cirrhosis of the liver, and 1 had a normal liver, whereas the remaining 39 had
      chronic hepatitis. Two patients who lost both anti-HCV-1 and HCV RNA showed a
      normal liver. Of two patients who lost only anti-HCV-1 one progressed to
      hepatocellular carcinoma and one to chronic hepatitis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1384113
TI  - Autoantibodies to the nuclear Sp100 protein in primary biliary cirrhosis and
      associated diseases: epitope specificity and immunoglobulin class distribution.
AB  - Sp100, a protein with a dot-like intranuclear localization in immunofluorescence
      microscopy, is a major target for patient autoantibodies in primary biliary
      cirrhosis (PBC) and occasionally in rheumatic disorders. The human Sp100 cDNA has
      recently been cloned, and the deduced amino acid sequence was found to contain
      sequence similarities with an MHC class I domain and several transacting
      regulatory proteins, including HIV-1 nef proteins. In this study, recombinant
      Sp100 fusion proteins were used to differentiate the immunoglobulin isotypes and
      to map the epitopes involved in the anti-Sp100 autoimmune response. PBC patients
      developed IgG as well as IgM and/or IgA class anti-Sp100 autoantibodies whereas
      most patients with rheumatic diseases developed IgG class autoantibodies only.
      For epitope mapping, truncated versions of the Sp100 protein were probed for
      immunoreactivity in ELISA and immunoblotting. With 55 sera, 17 different reaction
      patterns were obtained, and at least three non-overlapping major autoantigenic
      domains were recognized by the majority of sera. One domain, which contains the
      sequence similarity with HIV nef proteins, was recognized by all anti-Sp100 sera
      and harbours multiple, in part discontinuous, epitopes. These data demonstrate a
      heterogeneous and patient-specific anti-Sp100 autoimmune response which is
      antigen-driven and, at least in terms of isotype composition, different in PBC
      and non-PBC patients.

PMID- 1384114
TI  - Interleukin 4 and tumour necrosis factor alpha induce different adhesion pathways
      in endothelial cells for the binding of peripheral blood lymphocytes.
AB  - We demonstrated that tumour necrosis factor alpha (TNF-alpha) and interleukin 4
      (IL-4) increased endothelial cell (EC) adhesiveness for peripheral blood
      lymphocytes (PBL) by promoting transcription and protein synthesis. The different
      kinetics observed with TNF-alpha and IL-4 suggest the involvement of different
      adhesion molecules. Blocking adhesion assays and immunofluorescence analysis
      showed that PBL adhesion to endothelial cells involves different pair adhesion
      molecules. Whereas IL-4 promoted an LFA-1-dependent/ICAM-1-independent adhesion
      pathway on EC, TNF-alpha stimulated an LFA-1-dependent/ICAM-1-dependent adhesion
      pathway on EC. In contrast, VLA-4/VCAM-1 molecules were involved in PBL adhesion
      both to IL-4 and to TNF-alpha-stimulated EC. Finally, we found that a CD2
      dependent/LFA-3-independent adhesion pathway was mainly involved in IL-4
      stimulated EC.

PMID- 1384115
TI  - Analysis of mature guinea pig T cells with a monoclonal antibody directed against
      a framework determinant of the T-cell receptor for antigen.
AB  - Rats were immunized with guinea pig T lymphocytes and the spleen cells were fused
      with cells of a mouse myeloma line. The resulting hybrids were screened for the
      production of antibodies selectively reacting with guinea pig T cells. The
      monoclonal antibody (MoAb) H159 was analysed in detail because it bound to T
      lymphocytes, but not to B lymphocytes or macrophages. Cellular ELISA,
      cytofluorometry and immunohistology revealed that the antigen detected by H159 is
      selectively expressed on the majority of peripheral mature T lymphocytes (about
      95%). In contrast, it stained only a minor population of thymocytes in FACS
      analysis. H159 precipitated from NP40 lysate of T cells a protein with a
      molecular weight of about 90 kDa when separated under non-reducing conditions in
      SDS-PAGE. Under reducing conditions bands with molecular weights of about 50 kDa
      were found. After binding to anti-rat Ig coated beads, the MoAb H159 had a
      mitogenic effect for guinea pig T lymphocytes whereas soluble MoAb H159 in the
      presence or absence of macrophages was not mitogenic. The cellular expression and
      molecular characteristics of the H159 antigen together with the mitogenic
      activity of the antibody for T cells indicate that the MoAb H159 recognizes the
      guinea pig T-cell receptor for antigen via a constant region determinant.

PMID- 1384116
TI  - Fresh, frozen, or decalcified bone grafts: a study of early vascularisation and
      mineralisation of allogeneic and syngeneic bone grafts in rats.
AB  - The incorporation of syngeneic and allogeneic bone grafts pretreated by freezing
      or demineralisation was studied in 10 rats. Fresh, decalcified, or frozen
      cancellous bone of syngeneic or allogeneic origin was transplanted to
      intramuscular pouches. Revascularisation was evaluated with radioactive
      microspheres; formation of new bone was assessed by incorporation of strontium,
      and resorption was assessed by measuring the reduction of graft weight. Three
      weeks after grafting, fresh syngeneic and allogeneic bone differed significantly
      in all three variables. Frozen syngeneic bone was revascularised significantly
      better than frozen allogeneic bone, but there was no difference in formation of
      new bone or resorption. There were no significant differences between syngeneic
      and allogeneic decalcified bone in any of the variables studied. We conclude that
      differences in incorporation between syngeneic and allogeneic bone grafts are
      reduced by pretreatment with deep-freezing or demineralisation. Both forms of
      pretreatment affect the incorporation of the grafts.

PMID- 1384117
TI  - [Anti-arrhythmia treatment using L-carnitine in acute myocardial infarct].
AB  - Carnitine, a quaternary amine (3-hydroxy-4-N-trimethylaminobutyric acid), plays
      an important physiologic role in fatty acid transport and metabolism as well as
      in energy production of the myocardial cell. L-carnitine in high doses has been
      postulated to have an antiarrhythmic effect and this has also been clinically
      proven. We studied 20 patients with acute myocardial infarction (AMI), 4-12 hours
      after onset of pain. The patients were randomized and treated double-blind with 5
      g L-carnitine (n = 12) or placebo (n = 8) at hours 0, 12, 24, 36, and with 2 x 3
      g on days 3 to 7 by intravenous infusion over 2 hours. The two groups were
      similar for age, sex, infarct site, maximum CPK and conventional antiarrhythmic
      therapy. 24-hour Holter-ECG was performed on days 1, 2 and 7 and showed no
      significant difference between the two groups with respect to incidence of
      ventricular premature beats (VPB) per hour. On the second day following AMI,
      however, only 4 of 12 carnitine-treated patients showed high-grade VPB (Lown IVa
      and IVb), in comparison with 7 of 8 patients in the placebo group. The difference
      is significant: p = 0.028 (Fisher's Exact Test). Carnitine was well tolerated and
      the efficacy demonstrated on the second day following AMI must be interpreted
      with caution.

PMID- 1384118
TI  - Kinetics of hydroxyethyl starch in horses.
AB  - In a controlled study, the distribution and elimination kinetics of hydroxyethyl
      starch as well as clinically relevant parameters were determined in horses. The
      half-life of the first phase was 5.59 hours, that of the second phase 122.22
      hours. During the first phase, hydroxyethyl starch persisted almost exclusively
      intravascularly. The results of this study are largely in agreement with those in
      human beings. Thus, routes of elimination, duration of plasma-expanding action,
      distribution volume and redistribution kinetics in horses and human beings are
      very similar. However, the elimination kinetics of the second phase and the
      behavior of serum amylase appear to be equine-specific. Coagulation is barley
      influenced by the administration of hydroxyethyl starch. The results of this
      study confirm that hydroxyethyl starch is very suitable for use as a plasma
      expander in horses.

PMID- 1384119
TI  - [The diversity and the biological significance of receptor subtype in the central
      nervous system].

PMID- 1384120
TI  - [Advances in research on subtypes of muscarinic receptor].

PMID- 1384121
TI  - [Negative regulators of cell growth].

PMID- 1384122
TI  - [Neurotransmitters and its physiological effects in the nucleus fasciculi
      solitarii].

PMID- 1384123
TI  - [Immuno-modulatory effects of substance P].

PMID- 1384124
TI  - Butenes and butadiene in urban air.
AB  - Samples of urban air hydrocarbons were taken on specifically made adsorbent
      cartridges and analysed by gas chromatography after thermal desorption. The four
      isomeric butenes and 1,3-butadiene were favourably resolved and separated from
      the abundant alkanes on an aluminium oxide PLOT column. The concentrations of
      butadiene, reflecting outdoor urban exposure, were in the range of 0.5-5
      micrograms/m3. An approximate 1:4 ratio was observed between butadiene and
      propene which both originate predominantly from vehicle exhaust. The four butenes
      made up approximately 50% of the propene concentration in exhaust-polluted air,
      with methylpropene greater than 1-butene greater than trans-2-butene greater than
      cis-2-butene. Petrol vapour contributed less than exhaust but about five times
      more to the 2-butenes than to methylpropene and 1-butene. The highest exposure
      levels of butadiene and butenes were consistently observed in the vicinity of
      exhaust pipes and petrol-fuelled vehicles.

PMID- 1384125
TI  - DDT and HCH residues in indoor air arising from their use in malaria control
      programmes.
AB  - Samples of air from rooms in a residential and rural environment, treated with
      either DDT or HCH at rates recommended for mosquito control under the National
      Malaria Eradication Programme of India, i.e. 2 and 3 g m-2, respectively, were
      analyzed for the residues of these insecticides. During the 8-month sampling
      period, DDT and HCH levels in indoor air ranged from 1.0 to 14.6 and 0.9 to
      2000.1 micrograms m-3, respectively. After an initial fall, residues of DDT
      showed an increase again and were 5.9 micrograms m-3 in samples collected 240
      days after the initial application. In contrast, HCH residues declined at a fast
      rate in a few days after application and remained low at the time of subsequent
      samplings. HCH residues were present chiefly in the vapour phase throughout the
      study. Thirty-four to seventy-eight percent of DDT residues were found in the
      particulate phase in the samples collected up to 64 days after its application
      and exclusively in the vapour phase at the time of later samplings. Apart from
      the contamination of food and feed commodities stored in premises treated for
      malaria control by absorption of insecticides present in the indoor atmosphere,
      the residues of these persistent compounds in air are also likely to result in
      low level pollution of the surrounding and distant environmental media by their
      dispersion in the global ecosystem.

PMID- 1384126
TI  - Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase.
AB  - Entry into mitosis in Schizosaccharomyces pombe is negatively regulated by the
      wee1+ gene, which encodes a protein kinase with serine-, theonine-, and tyrosine
      phosphorylating activities. The wee1+ kinase negatively regulates mitosis by
      phosphorylating p34cdc2 on tyrosine 15, thereby inactivating the p34cdc2-cyclin B
      complex. The human homolog of the wee1+ gene (WEE1Hu) was overproduced in
      bacteria and assayed in an in vitro system. Unlike its fission yeast homolog, the
      product of the WEE1Hu gene encoded a tyrosine-specific protein kinase. The human
      WEE1 kinase phosphorylated the p34cdc2-cyclin B complex on tyrosine 15 but not on
      threonine 14 in vitro and inactivated the p34cdc2-cyclin B kinase. This
      inhibition was reversed by the human Cdc25C protein, which catalyzed the
      dephosphorylation of p34cdc2. These results indicate that the product of the
      WEE1Hu gene directly regulates the p34cdc2-cyclin B complex in human cells and
      that a kinase other than that encoded by WEE1Hu phosphorylates p34cdc2 on
      threonine 14.

PMID- 1384127
TI  - Circadian clock genes are ticking.

PMID- 1384128
TI  - Ion channel structure and function.

PMID- 1384129
TI  - Inhibition of neutrophil chemokinesis on vitronectin by inhibitors of
      calcineurin.
AB  - Migration of human polymorphonuclear neutrophils on vitronectin is dependent on
      repeated transient increases in the concentration of intracellular free calcium
      ([Ca2+]i). A specific peptide inhibitor of the Ca(2+)-calmodulin-dependent
      phosphatase calcineurin was introduced into the cytoplasm of neutrophils. The
      peptide inhibited neutrophil migration on vitronectin by interfering with the
      release of the cells from sites of attachment. A similar reduction in motility on
      vitronectin occurred when cells were treated with the immunosuppressant FK506,
      which also inhibits calcineurin when bound to its binding protein, FKBP. These
      results indicate that a rise in [Ca2+]i reduces integrin-mediated adhesion to
      vitronectin by a mechanism that requires calcineurin activity.

PMID- 1384130
TI  - Acetylcholine receptor channel structure probed in cysteine-substitution mutants.
AB  - In order to understand the structural bases of ion conduction, ion selectivity,
      and gating in the nicotinic acetylcholine receptor, mutagenesis and covalent
      modification were combined to identify the amino acid residues that line the
      channel. The side chains of alternate residues--Ser248, Leu250, Ser252, and
      Thr254--in M2, a membrane-spanning segment of the alpha subunit, are exposed in
      the closed channel. Thus alpha 248-254 probably forms a beta strand, and the gate
      is closer to the cytoplasmic end of the channel than any of these residues. On
      channel opening, Leu251 is also exposed. These results lead to a revised view of
      the closed and open channel structures.

PMID- 1384132
TI  - Seppuku and autoimmunity.

PMID- 1384131
TI  - Effects of kinesin mutations on neuronal functions.
AB  - Kinesin is believed to generate force for the movement of organelles in
      anterograde axonal transport. The identification of genes that encode kinesin
      like proteins suggests that other motors may provide anterograde force instead of
      or in addition to kinesin. To gain insight into the specific functions of
      kinesin, the effects of mutations in the kinesin heavy chain gene (khc) on the
      physiology and ultrastructure of Drosophila larval neurons were studied.
      Mutations in khc impair both action potential propagation in axons and
      neurotransmitter release at nerve terminals but have no apparent effect on the
      concentration of synaptic vesicles in nerve terminal cytoplasm. Thus kinesin is
      required in vivo for normal neuronal function and may be active in the transport
      of ion channels and components of the synaptic release machinery to their
      appropriate cellular locations. Kinesin appears not to be required for the
      anterograde transport of synaptic vesicles or their components.

PMID- 1384133
TI  - Does hyaluronan have a role in endothelial cell proliferation of the synovium?
AB  - Hyaluranate (HA) is a major constituent of synovial fluid, but its concentration
      and molecular size differ in normal and inflamed joints. HA can induce or inhibit
      angiogenesis depending on both its size and its concentration. Endothelial-cell
      endocytose-labeled macromolecular HA and HA oligosaccharides and binding studies
      have identified an HA-specific receptor on the endothelial cell surface (KD, 10(
      10) mol/L; approximately 2,000/cell). The molecular weight of HA-binding proteins
      was found to be 90 to 125, 78, and 46 kd.

PMID- 1384134
TI  - Non-Hodgkin's lymphomas: a review of the M.D. Anderson experience.
AB  - The approach we have followed in developing treatment strategies for lymphoma
      consists of testing new combinations in patients with recurrent disease and, if
      these are found to be effective, advancing them to front-line therapy. Three
      series of salvage regimens tested at the M. D. Anderson Cancer Center (MDACC)
      will be described. These were initially based on ifosfamide/etoposide, later on
      high-dose cytarabine/cisplatin, and more recently on a novel strategy that first
      uses MINE (mesna/ifosfamide/Novantrone [mitoxantrone; Lederle International,
      Wayne, NJ]/etoposide) for induction of remission and, following the attainment of
      the maximum response to MINE, changes treatment to a non--cross-resistant
      combination known as ESHAP (etoposide/Solu-medrol ([methylprednisolone]/high-dose
      cytarabine/cisplatin). The front-line management of intermediate-grade lymphoma
      at MDACC currently is based on prognostic factors. The criteria for selecting
      categories of less favorable patients will be discussed. A new regimen,
      alternating triple therapy based on three non--cross-resistant drug regimens,
      currently is being explored for these patients. Already this regimen has shown an
      early advantage in the worst category of cases, those with M.D. Anderson stage D
      (high tumor burden, high levels of lactate dehydrogenase). The data, however,
      remain preliminary.

PMID- 1384135
TI  - Etoposide, ifosfamide, and methotrexate combination chemotherapy for aggressive
      non-Hodgkin's lymphomas after failure of the LNH 84 regimen.
AB  - We assessed the efficacy and tolerability of VIM
      (etoposide/ifosfamide/methotrexate) combination therapy in 24 patients who were
      failing the treatment protocol of the Lymphomes Non Hodgkiniens (LNH) 84 study.
      Eight patients were refractory to the LNH 84 induction cycles, but ten achieved a
      partial response (PR). The six remaining patients attained complete response (CR)
      after LNH 84 induction, but relapsed either during consolidation therapy or after
      completing the whole program. Twenty-three patients are evaluable for response.
      The VIM regimen provided a CR rate of 43% and a PR rate of 17%. Treatment failed
      in nine cases (39%). The CR rate was particularly high (67%) in the group of
      patients who had PR with LNH 84 induction treatment. Of the ten who had attained
      CR, five relapsed after 4 to 42 months and five are still alive with no evidence
      of disease after 29 to 62 months. VIM therapy was well tolerated. A total of 101
      VIM courses were given. Myelotoxicity was the most common side effect. Grade 3 or
      4 cytopenia was recorded after 11% of the cycles. Among eight infectious episodes
      recorded, one was fatal. This study demonstrates that CR and long disease-free
      survival are obtainable with the VIM regimen in a small number of patients
      failing a high-dose doxorubicin-containing first-line treatment.

PMID- 1384137
TI  - Current perspectives on the use of bleomycin. Introduction.

PMID- 1384136
TI  - Carboplatin in small cell lung cancer: the Royal Marsden Hospital experience.
AB  - A series of studies has been carried out to evaluate and document the value of
      carboplatin in the treatment of patients with small cell lung cancer (SCLC).
      Encouraging response rates but disappointingly short response durations with both
      single-agent carboplatin and combination carboplatin/etoposide led to the use of
      more intensive study regimens. A six-course, dose-intensive study of combination
      carboplatin/etoposide/ifosfamide in good-prognosis patients resulted in a 97%
      objective response rate (31 of 32 patients), including 17 (53%) complete
      responses. However, the toxicity associated with this regimen was expectedly
      high. In a subsequent phase I dose-escalation study of carboplatin in SCLC, non
      small cell lung cancer, and mesothelioma, patients received 800, 1,200, or 1,600
      mg/m2 carboplatin given as a 1-hour intravenous infusion. Five of the seven SCLC
      patients achieved a complete or partial response, but no responses were seen
      among the other patients. The major toxicity noted was myelosuppression and,
      while treatment was well tolerated, toxicity was more pronounced at the higher
      doses. The role of carboplatin as palliative therapy for SCLC patients with
      advanced disease or poor performance status is currently under investigation with
      a regimen containing carboplatin/methotrexate/vinblastine. In light of the
      results of these several studies, it is apparent that carboplatin is an extremely
      active agent for treatment of SCLC and is not associated with the nephropathy,
      neuropathy, or severe nausea and vomiting induced by its parent compound,
      cisplatin. Further study of carboplatin as high-dose therapy, in dose-intensive
      combination regimens, and as palliative treatment is recommended.

PMID- 1384138
TI  - Current perspectives on the use of bleomycin. Symposium proceedings. Key
      Biscayne, Florida, February 22-23, 1991.

PMID- 1384139
TI  - Chemotherapy of male and female germ cell tumors.
AB  - Germ cell tumors of testicular origin are virtually always curable with modern
      therapy that appropriately integrates chemotherapy and surgery. Clinical trials
      of chemotherapy in patients with disseminated disease now separate those with
      limited metastatic disease and an excellent prognosis from those with bulky tumor
      and a less favorable prognosis. In the former group, it has been shown that three
      courses of BEP (bleomycin/etoposide/cisplatin) are therapeutically comparable to
      four courses. The next generation study compared BEP with a similar regimen with
      the bleomycin omitted. Early results of this study suggest that deletion of
      bleomycin worsens outcome. Other studies have addressed the same question but
      have used four courses of this agent. Ovarian germ cell tumors have been less
      well studied but are largely curable with surgery and chemotherapy. The specific
      regimens used are similar to their testis tumor counterparts. All patients with
      completely resected tumor should receive adjuvant chemotherapy; virtually all
      will remain cancer free. Of course, patients with advanced disease should also
      receive chemotherapy. Results are generally good in these patients, but probably
      less so than in testis tumor patients with similar tumor volume.

PMID- 1384140
TI  - Treatment of recurrent and metastatic head and neck cancer with
      cisplatin/etoposide/bleomycin.
AB  - Cisplatin/etoposide/bleomycin (DEB) was given as an outpatient regimen in a novel
      weekly schedule to 27 patients with recurrent and/or widely metastatic cancer of
      the head and neck region. Six of these patients also received mitomycin (DEB/M)
      when their disease failed to respond after at least three weekly DEB doses. All
      but three patients had been treated previously with radiotherapy directed to the
      primary site and regional nodal disease; four had also received chemotherapy with
      cisplatin or carboplatin. Before treatment with DEB, 19 patients had distant
      metastases. Of an intended 12 doses per patient, a mean of 8.2 was achieved.
      Myelosuppression was the major toxicity, with neutropenia in 45% of patients and
      significant anemia in 26%. The overall response rate to DEB in 27 patients was
      59%, increasing to 70% after the addition of mitomycin. There were two complete
      and 17 partial responses. The median duration of response was 12 weeks and median
      survival was 6 months, with 20% of patients surviving 1 year. We conclude that
      the relatively short survival time together with the significant toxicity of the
      DEB/M regimen does not warrant its routine use in clinical practice. However,
      this regimen, or one patterned on it, should be evaluated in combination with
      radiotherapy as the initial treatment for selected patients with previously
      untreated head and neck cancer.

PMID- 1384141
TI  - Bleomycin pharmacology: mechanism of action and resistance, and clinical
      pharmacokinetics.
AB  - Bleomycin is a glycopeptide antibiotic with a unique mechanism of antitumor
      activity. The drug binds to guanosine-cytosine-rich portions of DNA via
      association of the "S" tripeptide and by partial intercalation of the bithiazole
      rings. A group of five nitrogen atoms arranged in a square-pyramidal conformation
      binds divalent metals including iron, the active ligand, and copper, an inactive
      ligand. Molecular oxygen, bound by the iron, can produce highly reactive free
      radicals and Fe(III). The free radicals produce DNA single-strand breaks at 3'-4'
      bonds in deoxyribose. This yields free base propenals, especially of thymine:
      cytotoxicity is cell-cycle-phase specific for G2 phase. In humans, bleomycin is
      rapidly eliminated primarily by renal excretion. This accounts for approximately
      half of a dose. In patients with renal compromise or extensive prior cisplatin
      therapy, the drug half-life can extend from 2 to 4 hours up to 21 hours. Thus,
      dose adjustments are needed when creatinine clearance is less than or equal to 3N
      mL/min. Finally, resistance to bleomycin in normal tissues can be correlated with
      the presence of a bleomycin hydrolase enzyme, which is in the cysteine proteinase
      family. The enzyme replaces a terminal amine with a hydroxyl, thereby inhibiting
      iron binding and cytotoxic activity. The low concentration of enzyme in the skin
      and lung may explain the unique sensitivity of these tissues to bleomycin
      toxicity. However, correlation of hydrolase levels with tumor cell sensitivity
      has thus far been negative.

PMID- 1384142
TI  - Treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma using
      bleomycin-containing combination chemotherapy regimens.
AB  - Ninety-nine patients with advanced epidemic Kaposi's sarcoma were treated with
      bleomycin-containing regimens: 30 received bleomycin and vincristine (BV) and 69
      received doxorubicin, bleomycin, and vincristine. Treatment regimens were well
      tolerated, with response rates ranging from 76% to 81%. However, neutropenia
      developed even with the relatively nonmyelotoxic BV regimen. Twenty-eight of the
      99 patients (28%) were evaluated for pulmonary function prior to, during, and
      after completion of combination chemotherapy to assess pulmonary toxicity
      commonly associated with bleomycin. The carbon monoxide diffusion capacity (DLCO)
      was the only measurement that showed significant changes prior to and after
      completion of therapy (P = .0003). Moreover, patients receiving more than 100
      cumulative units of bleomycin experienced significantly greater declines in DLCO
      measurements than those receiving lower cumulative doses (P = .0067). No patient,
      however, developed clinically significant pulmonary toxicity attributable to
      bleomycin, with individual cumulative bleomycin doses ranging from 10 to 313 U
      (median, 112 U). We conclude that bleomycin is active and safe in the treatment
      of Kaposi's sarcoma, and close monitoring of pulmonary function is warranted with
      cumulative doses exceeding 100 U.

PMID- 1384143
TI  - ABVD in the treatment of Hodgkin's disease.
AB  - This paper summarizes the clinical results achieved at the Milan Cancer Institute
      in advanced Hodgkin's disease through successive randomized studies performed
      during the last two decades. Long-term results confirm the therapeutic activity
      of a regimen containing bleomycin and doxorubicin, such as ABVD
      (doxorubicin/bleomycin/vinblastine/dacarbazine), as salvage treatment and as
      primary chemotherapy, either when combined with radiation or cyclically
      alternated with MOPP (mechlorethamine/vincristine/procarbazine/prednisone).
      Delayed iatrogenic morbidity (namely, sterility and leukemogenesis) was less
      frequently documented in ABVD-treated patients compared with MOPP-treated
      patients. Nevertheless, bleomycin- and anthracycline-containing regimens can be
      refined in the attempt to further decrease iatrogenic toxicity.

PMID- 1384144
TI  - Bleomycin in non-Hodgkin's lymphoma.
AB  - Bleomycin is a cell-cycle--specific chemotherapeutic agent, with several
      interesting properties, that lends itself to use in combination chemotherapeutic
      protocols, especially those for malignant lymphomas. In the following article,
      bleomycin's use as a single agent and subsequently in three generations of
      combination chemotherapeutic regimens is reviewed. Bleomycin's lack of
      myelosuppression and its tendency to concentrate in lymphoid tissue while
      maintaining tolerable toxicities has been the rationale for its incorporation
      into more aggressive treatment regimens.

PMID- 1384145
TI  - The role of cisplatin/bleomycin-based chemotherapy in the treatment of poorly
      differentiated carcinoma of unknown primary site.
AB  - Between 1978 and 1990, 173 patients with poorly differentiated carcinoma or
      poorly differentiated adenocarcinoma of unknown primary site were treated with
      bleomycin-containing regimens at Vanderbilt University Medical Center. Patients
      were prospectively identified based on light microscopy findings. The median age
      of patients was 39 years; 78% were male and 76% had metastatic tumors in two or
      more sites. Dominant tumor location was the mediastinum, retroperitoneum, or
      peripheral lymph nodes in 82 patients (47%). Between 1978 and 1985, patients
      received cisplatin 20 mg/m2 intravenously (IV) days 1 through 5, vinblastine 0.15
      mg/kg IV days 1 and 2, and bleomycin 30 U IV weekly. In 1986, etoposide 100 mg/m2
      IV days 1 through 5 replaced vinblastine in the regimen. Responding patients
      received four courses of therapy at 3-week intervals. One hundred thirteen
      patients (65%) had a major response to therapy, including 47 (27%) complete
      responses. At present, 27 patients are disease free at a median of 78 months
      posttherapy (range, 11 to 142 months); an additional patient was lost to follow
      up while in complete response. Median survival of the entire group was 11 months,
      with a 12-year actuarial disease-free survival of 16%. Combination chemotherapy
      with cisplatin/bleomycin and either vinblastine or etoposide is highly active in
      patients with poorly differentiated carcinoma of unknown primary site and is
      curative in a minority of these patients. A trial of this therapy should be
      considered in all such patients.

PMID- 1384146
TI  - Bleomycin and tetracycline in malignant pleural effusions: a review.
AB  - Pleural effusions remain a distressing and symptomatic problem in cancer
      patients. Once a malignant pleural effusion is diagnosed, appropriate therapy may
      provide symptomatic relief and improved quality of life. In this paper, we review
      previous data on chest tube drainage and pleurodesis in patients with malignant
      pleural effusions. A comparison is made of the various sclerosing agents.
      Specifically, recent data from a study comparing bleomycin and tetracycline as
      sclerosing agents are discussed. These data show a clear advantage with bleomycin
      at both 30-day and 90-day end points--30-day recurrence, 36% versus 67%; 90-day
      recurrence, 30% versus 53%.

PMID- 1384147
TI  - Bleomycin pulmonary toxicity: current status and future directions.
AB  - Bleomycin is a polypeptide antibiotic that has been used in clinical cancer
      chemotherapy for over 20 years. Risk factors associated with bleomycin include
      total dose of drug, age of patient, high-dose oxygen therapy during surgery, and
      prior and concomitant radiation therapy. Attempts at developing predictive and
      precise monitoring systems have not been completely successful; however, the
      combined use of clinical and laboratory tests, such as the DLCO test, can be used
      to permit safe administration of the drug. Recent work has emphasized the
      development of new analogues, such as liblomycin, that appear to possess less
      pulmonary toxicity than does bleomycin, and has focused on understanding the
      pathogenesis of pulmonary toxicity, particularly as it relates to the immune
      system.

PMID- 1384148
TI  - Experience with bleomycin, ifosfamide, and cisplatin in primary and recurrent
      cervical cancer.
AB  - The unfavorable prognosis for patients with advanced and bulky early stage cancer
      of the cervix may be improved by initial neoadjuvant cytoreductive chemotherapy.
      In a phase II study using ifosfamide in combination with cisplatin/bleomycin
      (BIP) in advanced and recurrent cervical cancer, we demonstrated a response rate
      of 69%. To determine whether this high response rate was a result of patient
      selection, and to assess the influence of combination chemotherapy on survival in
      patients with recurrent disease, a retrospective analysis of five phase II
      studies of bleomycin, ifosfamide, and cisplatin combinations was performed. The
      type of chemotherapy regimen (BIP v others) was the most significant factor in
      determining the likelihood of response. Combination chemotherapy did not appear
      to confer a survival advantage in patients with recurrent disease. The BIP
      regimen produced rapid responses with acceptable toxicity, and had potential for
      use as neoadjuvant therapy prior to radical radiotherapy in patients with
      advanced and bulky early stage disease. In an initial pilot study of this
      approach, 13 of 19 patients (68%) with primary inoperable disease had significant
      tumor regression prior to radical local radiotherapy. Interim analysis of the
      first 66 patients entered into a randomized study evaluating this approach has
      shown complete clinical tumor resolution after radical radiotherapy in 24 of 32
      patients (75%) treated with up to three cycles of BIP prior to radiotherapy
      compared with 19 of 34 patients (56%) treated with radiotherapy alone. There has
      been no evidence that neoadjuvant chemotherapy enhances the acute toxic effects
      of pelvic radiotherapy. Therefore, this approach has potential to improve
      therapeutic outcome in patients with poor-prognosis primary disease.

PMID- 1384150
TI  - Patient classification, a key to evaluate pain treatment: a psychological study
      in chronic low back pain patients.
AB  - It has been proposed that pain treatment evaluation is hindered by heterogeneous
      properties of patient samples. Therefore, to facilitate pain treatment evaluation
      in this psychological study, a heterogeneous group of chronic low back pain
      patients was classified into more homogeneous subgroups. Two designs were used to
      compare the outcome by the "functioning activation" and the "spa resort" type of
      rehabilitation. In the first design, the outcome was compared in groups,
      clinically homogenized by sociodemographic variables and in respect to
      contraindications for heavy physical training. In the second design, the pain
      patient subgroups, homogenized by cluster analysis technique in accordance with
      the psychological profiles of functioning, were compared in their response to
      treatments. The results indicated that the outcome evaluation was facilitated by
      the latter design releasing more specific information about the effects of the
      program quality, the patient characteristics, and their interaction on the
      improvement by rehabilitation. It was concluded that in treatment outcome
      analysis, the subgroup's homogeneity must be considered.

PMID- 1384149
TI  - Hypersensitivity reactions.
AB  - All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and
      dactinomycin, have produced at least an isolated instance of a HSR. Certain
      drugs, such as L-asparaginase and mitomycin (administered intravesically), cause
      HSRs of significant degree in approximately 10% of patients. All four types of
      HSRs are represented in the reactions produced by antitumor drugs, although Type
      I is the most common. Some of the Type I reactions are IgE-mediated, and others
      are probably mediated by nonspecific release of vasoactive substances from
      targets such as mast cells. It is possible to continue therapy with some drugs,
      despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken.
      An example of this is provided by taxol in which the lengthening of the infusion
      time and the administration of preventive medication allowed some patients to
      continue taxol therapy. The mechanisms of the HSRs have been carefully assessed
      in only a minority of patients who sustained such toxicity. Such evaluation would
      increase our understanding of this form of drug toxicity and perhaps lead to
      means of effectively reducing the risk and severity.

PMID- 1384152
TI  - [Incidental carcinoma of the prostate. Study of 683 patients operated upon for
      benign prostatic hypertrophy].
AB  - During the period 1988-1990, 683 patients with diagnosis of benign prostatic
      hyperplasia underwent transvesical prostatectomy. The purpose of the study was to
      establish the possible presence of incidental carcinoma of the prostate (ICP).
      Prostatic tissue was studied with sections taken every 0.5 cm. The incidence of
      ICP was 12.00%. The mean age of patients was 73.5 years. 60.98% of tumors
      classified T1a, 39.02% T1b. No case of G3 tumor was observed while 92.68% of
      neoplasms was classified G1 and 7.32% G2. 74.95% of tumoral nests into the
      prostatic tissue had a breadth about one millimetre.

PMID- 1384151
TI  - Seroepidemiologic study of hepatitis C virus in sexually transmitted disease risk
      groups.
AB  - To identify the importance of heterosexual activity as a possible route for the
      transmission of the hepatitis C virus (HCV), a screening of antibodies against
      HCV (anti-HCV) was performed in 200 sexually transmitted disease patients with
      different risks for incurring genital infections as well as in 100 registered
      prostitutes. Out of all 300 persons tested, 14 cases of HCV infection were
      detected. Anti-HCV was present in 3 of the prostitutes and in 11 of the STD
      patients. Evaluating known risk factors, such as intravenous drug use or blood
      transfusion, 6 out of the 11 STD patients and all of the prostitutes in whom anti
      HCV was present were intravenous drug users and exhibited highly promiscuous
      behavior. Intravenous drug use was the probable means of acquisition in 9 of the
      14 subjects in whom anti-HCV was present, and homosexual promiscuous behavior was
      assumed to be the means of acquisition in another 2 subjects. In heterosexual
      patients engaging in high-risk behavior (high number of sexual partners and
      genital infections), the exclusion of intravenous drug use decreased the
      prevalence of anti-HCV from 12.1% to 4.1%, demonstrating no significant increase
      from the prevalence among low-risk persons. Most of the patients were screened
      for STDs, such as syphilis, Neisseria gonorrhoeae, Chlamydia trachomatis, human
      immunodeficiency virus (HIV), hepatitis B virus (HBV), trichomoniasis, and yeast
      infections. The highest rate of coinfection with anti-HCV was found in patients
      with serologic evidence of an HIV infection (50%).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1384153
TI  - [Can mepartricin be considered an antiandrogenic drug?].

PMID- 1384154
TI  - Combined isodose curves of high-dose rate interstitial brachytherapy with
      external-beam radiation therapy in pancreatic carcinoma.
AB  - From September 1989 until March 1992 nine patients with unresectable, though
      localized carcinoma of the pancreas were treated by a multimodality therapy
      consisting of palliative surgery, interstitial conformal brachytherapy in high
      dose rate mode (HDRBT) with iridium-192 up to 30 Gy and external-beam radiation
      therapy (EBRT) of about 52 Gy. Four patients simultaneously received two cycles
      of chemotherapy consisting of 5-FU and Leucovorin. Since high radiation doses are
      applied which are not tolerated in adjacent healthy tissues, doses to tumor and
      critical areas need to be known precisely and are to be adjusted before
      treatment. A three-dimensional imaging system is required. A self developed
      method combines the data of simulation radiographs and those of CT scans. The
      prescribed minimum target absorbed dose in HDRBT is adjusted to the target volume
      sparing organs at risk. The specialized quality assurance is adapted to this
      method. Differences between measured and calculated doses do not exceed 5%. The
      addition of isodoses of HDRBT and EBRT on CT scans is demonstrated. Due to
      patients' selection the treatment concept did not reveal any positive effects on
      survival. However, excellent palliative results were obtained without severe side
      effects.

PMID- 1384155
TI  - Maternal zinc and fetal neural tube defects.
AB  - Among the factors implicated in the heterogeneous etiology of neural tube defects
      (NTDs) is the trace element zinc (Zn). In a case-control study, we collected
      midtrimester maternal toenail samples for multiple trace element analyses,
      including Zn, which were assayed by neutron activation analysis. We studied 17
      women with NTD offspring and 1,787 controls. The crude OR for NTD comparing Zn
      values greater than normal range to normal Zn values was 3.2 (95% CI 1.1,9.7).
      These results were not materially affected when adjustment was made for folic
      acid supplementation. An overall increased risk for NTD associated with
      increasing toenail Zn was also evident. A matched subset of 17 cases and 73
      controls yielded a crude OR of 3.1 (95% CI 0.9,10.3) when cases with elevated Zn
      (greater than or equal to 120 ppm) were compared to those with normal Zn. Matched
      analyses controlling for folic acid supplements, family history of NTD, assay
      batch, age of mother and year of delivery yielded an OR of 5.0 (95% CI 1.1,21.6).
      This study reveals an association between increased toenail Zn in the second
      trimester of pregnancy and the risk of having a child with an NTD. Whether Zn
      sequestration has resulted in relative Zn deficiency at the site of neural tube
      closure remains uncertain.

PMID- 1384156
TI  - An unusual mosaic karyotype detected through prenatal diagnosis with duplication
      of 1q and 19p and associated teratoma development.
AB  - A 40-year-old white woman underwent amniocentesis for advanced maternal age at
      15.4 weeks gestation. Fetal chromosome analysis demonstrated two distinct cell
      lines: [46,XX,t(1;19)(p11;p11)]--10%; and [47,XX,t(1;19)(p11;p11) +
      der(1)t(1;19)(p11;q11)]--90%. The latter karyotype was trisomic for both 1q and
      19p. The mother carried the balanced translocation; the father had a normal
      karyotype. Amniotic fluid alpha-fetoprotein level was elevated and an
      acetylcholinesterase band was detected. Level II ultrasonography at 17 and 24
      weeks revealed several abnormalities, including a large facial cleft and a
      probable facial teratoma and intracranial tumor. Autopsy following pregnancy
      termination confirmed the presence of both. Chromosome evaluation of 172
      metaphases of both the epignathus and the intracranial teratoma demonstrated a
      predominance of the cell line with 47 chromosomes (166/172 = 96.5%), while from
      nonteratoma tissue (lung, liver, skin, and brain) only the balanced karyotype was
      detected. These observations suggest that the chromosomal imbalance is
      instrumental in the etiology of the teratoma.

PMID- 1384157
TI  - Fibrin gel network characteristics and coronary heart disease: relations to
      plasma fibrinogen concentration, acute phase protein, serum lipoproteins and
      coronary atherosclerosis.
AB  - The native fibrin gel structure formed in vitro from plasma samples was examined
      by liquid permeation of the hydrated fibrin gel networks in 18 men who had
      suffered a myocardial infarction before the age of 45 years and in 20 control
      subjects. Patients with an elevated plasma fibrinogen concentration had a
      considerably lower fibrin gel porosity (permeability coefficient, Ks) compared
      with patients with a normal plasma fibrinogen level and with controls. The
      calculated fiber mass-length ratio of the fibrin gel networks was decreased in
      both patient groups. Gel porosity differed markedly between individuals at a
      given plasma fibrinogen concentration. Fairly strong inverse correlations were
      found between plasma orosomucoid level on the one hand and Ks (r = -0.617, p less
      than 0.01) or fiber mass-length ratio (r = -0.499, p less than 0.05) on the
      other. The low density lipoprotein (LDL) cholesterol concentration also
      correlated inversely with Ks (r = -0.471, p less than 0.05) and fiber mass-length
      ratio (r = -0.522, p less than 0.05). Significant inverse relations, which were
      independent of plasma fibrinogen and lipoprotein concentrations, were detected
      between Ks (r = -0.519, p less than 0.05) and calculated fiber mass-length ratio
      (r = -0.723, p less than 0.001) and number and severity of coronary artery
      stenoses determined by angiography. A proneness to formation of tight, rigid and
      space-filling fibrin network structures with small pores thus appears to be
      associated with premature coronary artery disease.

PMID- 1384158
TI  - The ex vivo effect of preadsorbed vitronectin on platelet activation.
AB  - The activation of ex vivo canine platelets by preadsorbed vitronectin (VN) was
      sensitive not only to the polymer substrate utilized but also to the adsorption
      conditions employed. Lower levels of maximal platelet deposition were obtained
      for VN-coated silicone rubber (SR) than for other VN-coated substrates with
      comparable levels of adsorbed VN, but this effect was diminished with increased
      residence time of VN on the SR surface. Submonolayer and monolayer surface
      concentrations of VN elicited similar maximal levels of platelet deposition at
      both short (less than 3 h) and long (greater than 12 h) residence times, but
      thrombi were larger and more dense for the submonolayer surface concentrations.
      VN was also more effective in forming thrombi when adsorbed sequentially before
      albumin instead of after albumin. To further examine these differences in the
      nature of adsorbed VN between substrates and adsorption conditions, sodium
      dodecyl sulfate (SDS) elutability measurements and Fourier transform infrared
      spectroscopy with attenuated total reflectance optics (FTIR-ATR) evaluations of
      the adsorbed protein were performed. An SDS solution was able to remove a greater
      percentage of the VN which was adsorbed to a submonolayer than a monolayer
      surface concentration when SDS displacement was initiated immediately after
      adsorption was terminated. However, if the adsorbed protein was allowed to reside
      on the surface for a length of time before the introduction of the SDS displacing
      media, a greater percentage of the monolayer surface concentration was removed.
      The submonolayer surface concentration may be better able to increase its
      strength of contact with the surface during the added residence time than the
      monolayer surface concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384159
TI  - Progesterone regulation of plasminogen activator inhibitor 1 (PAI-1) antigen and
      mRNA levels in human endometrial stromal cells.
AB  - Plasminogen activator activity decreases in the endometrium in the secretory
      phase of the menstrual cycle. This is partly due to decreased release of
      urokinase plasminogen activator in response to progesterone. Plasminogen
      activator inhibitor type 1 (PAI-1) is an efficient inhibitor of both tissue-type
      and urokinase-type plasminogen activators, and may therefore be instrumental for
      the control of plasminogen activation. In this study we examined the effects of
      steroid hormones on PAI-1 release and PAI-1 mRNA levels in primary cultures of
      human endometrial stromal cells. In these cells the secretion of PAI-1 was
      increased by progesterone in a dose and time dependent way, but was not affected
      by estradiol. The progesterone induction of PAI-1 secretion was preceded by a 7-8
      fold increase of the steady state level of PAI-1 mRNA in the cells, suggesting
      that progesterone activates PAI-1 gene expression. Cultured endometrial glandular
      epithelial cells were found to release only insignificant amounts of PAI-1 with
      or without hormone treatment. The effect of progesterone on endometrial stromal
      cells was mimicked by DH-testosterone. However, while the response to
      progesterone was completely blocked by ZK112993, a potent antagonist of the
      progesterone receptor, the response to DH-testosterone was partially blocked by
      ZK112993, and partially by OH-flutamide, a potent antagonist of the androgen
      receptor. This suggests that a secretory response on PAI-1 expression is mediated
      via androgen receptors in endometrial tissue.

PMID- 1384160
TI  - Intercellular transport through a partially denuded arterial endothelial
      monolayer. Effect of platelets and PGI2.
AB  - Fluorescein Dextran (FD) was shown to be transported at increased rates through
      partially denuded endothelial monolayer. Platelet binding to the partially
      denuded monolayer lowered transport rates to those comparable with intact
      endothelium. Inhibition of transport by platelet binding was not affected by the
      addition of isocarbacyclin (a stable derivative of PGI2). This result suggests
      that adherent platelets at the partial denudation site are sufficient to suppress
      transport of FD.

PMID- 1384161
TI  - A monoclonal antibody (LK-4) which differentiates PLA1 from PLA2 platelet
      extracts but not intact platelets.
AB  - A unique murine monoclonal antibody (LK-4) is described which differentiates
      PLA1/PLA1 platelet extracts from PLA2/PLA2 and PLA1/PLA2 platelet extracts on
      solid phase ELISA and immunoblot at the 100kD GPIIIa location, but not on intact
      platelets. LK-4 reacts equally with intact PLA1/PLA2 and PLA2/PLA2 platelets.
      Adsorbtion of LK-4 with PLA1/PLA1 platelets results in loss of reactivity for
      intact platelets as well as platelet extracts on ELISA or immunoblot. LK-4
      inhibits platelet aggregation induced by ADP, epinephrine, collagen and thrombin,
      suggesting reactivity at or near the fibrinogen binding site on GPIIIa. It is
      suggested the LK-4 reacts with a conformation-induced common epitope for PLA1 and
      PLA2 on GPIIIa, with loss of this conformation for PLA2 GPIIIa following
      solubilization with Triton X-100.

PMID- 1384162
TI  - Purification of human alpha 2-plasmin inhibitor by a one-step immunoaffinity
      chromatography procedure.

PMID- 1384163
TI  - Okadaic acid and vanadate inhibit collagen-induced platelet aggregation; the
      functional relation of phosphatases on platelet aggregation.
AB  - The different specific inhibitors for phosphoserine/threonine and phosphotyrosine
      protein phosphatases were used to study the role of these protein phosphatases in
      collagen-platelet interaction. The collagen-induced platelet aggregation and the
      release reaction as measured ATP release were inhibited in a dose-dependent
      fashion by the addition of okadaic acid, a specific inhibitor of
      phosphoserine/threonine protein phosphatase 1 and 2A. The inhibition was also
      observed by the addition of a phosphotyrosine protein phosphatase inhibitor,
      vanadate. Suboptimal concentrations of both inhibitors together also inhibited
      collagen-induced platelet aggregation and release reaction in a concentration
      dependent fashion. These results suggest that collagen-platelet interaction is
      modulated by both protein phosphatases.

PMID- 1384164
TI  - [From endothelium-derived relaxing factor to L-arginine and nitrogen monoxide].
AB  - Endothelium-derived relaxing factor has been identified as nitric oxide. It was
      originally found to be released from endothelial cells, mediating vascular
      relaxation and platelet inhibitory action. Nitric oxide is formed enzymatically
      from L-arginine by nitric oxide synthase, and this enzyme has up to the present
      been demonstrated in endothelial cells, platelets, neutrophils, macrophages,
      neurons and smooth muscle cells. Both a constitutive and an inducible nitric
      oxide synthase have been identified, which may serve different
      physiological/pathophysiological purposes. The biological implications of nitric
      oxide have now been manifested, and the number of reports on its physiological
      role is rapidly increasing. Compounds which inhibit the formation of nitric oxide
      have become available, and this expanding field has created great interest
      amongst clinicians.

PMID- 1384165
TI  - Omentopexy for revascularization of free tracheal grafts in rats.
AB  - In rats, we examined the effect of an omentum wrapping on the vascularization of
      the trachea and on regeneration of the mucosal epithelium in the very early stage
      after free tracheal grafting. Two pieces of trachea were obtained from each donor
      rat. One piece was transplanted into the peritoneal cavity of the recipient rat
      and wrapped with omentum. The other piece was transplanted subcutaneously into
      the abdominal wall, without omentopexy. Recipients were sacrificed at random on
      days 1, 2, 3, and 4 after operation (5 rats/day). The increase of blood vessels
      rose significantly earlier in the omentopexy tracheas than in those without
      omentopexy (p less than 0.01), with all the former showing a normal ciliated,
      columnar epithelium in the membranous region of the trachea on day 4, accompanied
      by excellent epithelial regeneration in the cartilaginous region. These results
      suggest that omentopexy causes revascularization to occur earlier and to be
      completed in a shorter time, and that it also promotes epithelial regeneration
      following free tracheal grafting.

PMID- 1384166
TI  - The molecular basis for reactivity of anti-Cw1 and anti-Cw3 alloantisera with HLA
      B46 haplotypes.
AB  - HLA haplotypes containing the HLA-B46 allele react with both anti-Cw1 and anti
      Cw3 alloantisera, a pattern of reactivity defined as the Cw11 antigen and
      postulated to involve either a distinctive Cw11 allele or a duplicated HLA-C
      locus. From serological characterization of CIR cells transfected with B46 cDNA
      we now demonstrate that the anti-Cw3 reactivity with these haplotypes is solely
      due to the B46 molecule and not to an HLA-C molecule. Furthermore, isolation and
      characterization of HLA-C mRNA from cells expressing B46 strongly suggest that
      anti-Cw1 reactions are directed against the product of a conventional Cw1 allele.
      The antigenic cross-reactivities of B46 with B62 and Cw3 correlate with its
      chimaeric primary structure, which is identical to that of B62, except in the
      alpha 1 helix where it is identical to both Cw3 and Cw1. The structure,
      distribution and genetic linkage of B46 indicate it is of recent, Asian origin
      and is the result of a gene conversion, involving Cw1 as the donor gene and B62
      as the recipient. These results demonstrate that the Cw11 antigen neither
      corresponds to a novel HLA-C allele nor a duplicated HLA-C locus, but to a
      combination of epitopes contributed by linked Cw1 and B46 alleles. The nucleotide
      sequence we previously and erroneously attributed to a distinct Cw11 allele is
      now demonstrated to encode Cw8. Isolation of the cDNA clone with this sequence
      from a library made from a cell homozygous for the B46 haplotype was probably an
      artefact of contamination.

PMID- 1384167
TI  - A cytotoxic monoclonal human hybridoma antibody (TrJ3) against HLA-B44(12) and 
      B45(12).
AB  - We have generated a human monoclonal cytotoxic IgM lambda antibody (TrJ3) that
      reacted specifically with all lymphoblastoid B-cell lines expressing HLA-B44(12)
      and B45(12). TrJ3 hybridoma supernatant was suitable for HLA-B12 typing of
      freshly isolated blood mononuclear cells. Analysis of available amino acid
      sequences of HLA-B molecules indicated that the alpha 1 domain does not contain
      the TrJ3 serological epitope. Since HLA-B44 is associated with a unique serine
      residue at position 167 that points towards the peptide binding groove, we
      propose that S167 of the alpha 2 domain helix is a critical part of the TrJ3
      epitope.

PMID- 1384168
TI  - Mechanism of cell swelling of HeLa cells in an isosmotic Na(+)-free, high-K+
      medium: study on the K+ transport pathways.
AB  - The K+ content and the free Ca2+ concentration ([Ca2+]c) in HeLa cells began to
      increase after a latent period following medium change to an isosmotic Na(+)
      free, high-K+ medium in the presence of 10-100 microM ouabain. These increases
      were accompanied by cell swelling, and stimulated by the addition of 1 microM
      ionomycin, whereas treatment with 1 mM quinine significantly inhibited the net K+
      uptake. [Ca2+]c was slightly decreased, but the K+ uptake was unaffected in the
      Ca(2+)-free, high-K+ medium. However, when [Ca2+]c was extremely reduced by
      preloading 5 microM BAPTA-AM, the K+ uptake decreased to a level attained in the
      presence of quinine. Addition of DIDS and substitution with NO3- or SCN- for
      medium Cl- inhibited the K+ uptake to similar extents, and their effects were
      less strong than that of quinine. Substitution of medium Cl- with an impermeable
      anion gluconate completely inhibited the K+ uptake. Therefore, we conclude that
      cell swelling in the high-K+ medium is associated with K+ uptake mediated in
      greater part by quinine-sensitive and in smaller part by -insensitive pathway.
      The former pathway depends on cellular Ca2+ and its major component is Cl(-)
      dependent, whereas the latter is independent of the Ca2+ and unselective for
      anions.

PMID- 1384169
TI  - Modulation of ganglioside expression in human melanoma cell lines; increased
      resistance to chemo- and radiation treatment.
AB  - Cell surface gangliosides in human melanoma cell lines were modulated by
      pretreatment and adaptation to 6-thioguanine and 5-bromo-deoxyuridine. Chemo- and
      radiation sensitivities were compared in original cell lines and modulated cells
      by the human tumor colony-forming assay. Modulated cells showed decreased
      expression of cell surface GM2 and GD2 gangliosides. This reduction was
      correlated with increased resistance to bleomycin, vincristine, cisplatin and
      radiation treatment. These results suggest that cell surface GM2 and GD2
      ganglioside expression in human melanoma cells is intimately associated with
      several cellular biological properties, such as drug or radiation sensitivity and
      cellular differentiation.

PMID- 1384170
TI  - Alpha 2u-globulin is the only member of the lipocalin protein superfamily that
      binds to hyaline droplet inducing agents.
AB  - The rate-limiting step in chemically induced, male rat-specific hyaline droplet
      nephropathy is the reversible binding of a xenobiotic to alpha 2u-globulin. In
      this study, equilibrium saturation binding experiments were conducted to evaluate
      the in vitro binding of d-limonene-1,2-oxide (dLO) and 2,4,4-trimethyl-2-pentanol
      (TMP-OH) to alpha 2u-globulin and members of the alpha 2u-globulin protein
      superfamily. Both dLO and TMP-OH bound to alpha 2u-globulin, with Scatchard
      analysis yielding dissociation constants of 5.6 and 6.4 x 10(-7) M, respectively.
      The Bmax for binding (nmol bound/mg protein) was 50.7 and 61.1 for dLO and TMP
      OH, respectively, yielding a molar ratio of approximately 1 for both ligands. The
      ability of dLO and TMP-OH to bind to human-derived alpha 1-acid glycoprotein, rat
      derived retinol-binding protein, human protein-1, and bovine beta-lactoglobulin
      was also studied. These superfamily proteins are generally abundant in plasma,
      are freely filtered across the glomerulus, and can bind a wide range of ligands.
      However, neither dLO nor TMP-OH bound to any of the superfamily proteins. In
      contrast, under identical experimental conditions, alpha 1-acid glycoprotein did
      bind progesterone (Kd = 10(-6) M), whereas both beta-lactoglobulin and retinol
      binding protein bound retinol (Kd = 10(-8) M for both proteins). These results
      indicate that, under conditions where alpha 2u-globulin superfamily proteins bind
      to established ligands, the proteins do not interact with hyaline droplet
      inducing agents. Thus, the interaction between male rat-specific nephrotoxicants
      and alpha 2u-globulin is unique to this protein. More importantly, these results
      provide direct evidence that the presence of the alpha 2u-globulin superfamily
      proteins does not predispose humans to develop hyaline droplet nephropathy and
      renal cancer from this class of chemicals.

PMID- 1384171
TI  - Quantification of metallothionein isoforms using an enzyme-linked immunosorbent
      assay (ELISA) with two specific antisera.
AB  - The specificity of three populations of antibodies to the two metallothionein
      (MT) isoforms has been characterized using a competitive enzyme-linked
      immunosorbent assay (ELISA). A polyclonal sheep anti-MT-1 antibody (PAb 1) showed
      higher affinity to MT-1 than to MT-2 with I50 (concentrations required to achieve
      50% inhibition) being 18 and 480 ng for MT-1 and MT-2, respectively. Conversely,
      a polyclonal rabbit anti-MT-2 antibody (PAb 2) showed higher affinity to MT-2
      than to MT-1 (I50 being 250 and 15 ng for MT-1 and MT-2, respectively). A third
      antibody (PAb 3), isolated by removal of anti-MT-1 antibodies in PAB 2 by
      immunoaffinity purification, showed no cross-reactivity with MT-1. This result
      suggests that there are two populations of antibodies which cross-react
      specifically with the MT isoforms. Rat tissue MT concentrations were quantified
      by ELISA using the three different antibodies and silver-saturation method. The
      sum of MT isoform concentrations (ELISA estimation using antibodies PAb 1 and PAb
      3) were not significantly different (p < 0.05) from the total MT concentrations
      obtained by silver-saturation method. Therefore, the ELISA can be used to
      estimate the relative quantities of the two MT isoforms in rat tissues. The
      predominant isoform in rat tissues was MT-2 and the proportion of MT-1 increased
      with induced synthesis of MT by metal injection.

PMID- 1384172
TI  - A comparison of European High Test gasoline and PS-6 unleaded gasoline in their
      abilities to induce alpha 2u-globulin nephropathy and renal cell proliferation.
AB  - Male Fischer-344 rats were administered European High Test gasoline (EHT) (50-500
      mg/kg), PS-6 unleaded gasoline (UG) (16-500 mg/kg) or 2,2,4-trimethylpentane
      (TMP) (0.95-30 mg/kg) by gavage for ten consecutive days. To measure cell
      replication, rats were exposed to [3H]thymidine continuously over the last 7 days
      of the exposure period. Twenty-four hours after the final dose, protein droplet
      (PD) accumulation, alpha 2u-globulin (alpha 2u) concentration and the nuclear
      labeling index (LI), as a measure of cell replication, were measured in the
      kidneys of control and treated rats. Dose-related increases in PD, alpha 2u and
      cell replication were detected in the kidneys of rats treated with either
      gasoline mixture or TMP. The accumulation of PD and the increase in alpha 2u was
      greater in the kidneys of UG- and TMP-treated rats than in the kidneys of rats
      treated with EHT. These differences were attributed to the higher composition of
      branched hydrocarbons in UG, which have been shown to be the biologically active
      components for these endpoints. The extent of renal cell proliferation was
      similar in both EHT-, UG- and TMP-treated rats. This suggests that other
      components besides the branched hydrocarbons are responsible for the increased
      renal cell replication in EHT-treated rats.

PMID- 1384173
TI  - [A method for diagnosing drug-induced lesions of the oral mucosa by the change in
      the nucleolar apparatus of peripheral blood lymphocytes in cell cultures with the
      presumed allergen].

PMID- 1384174
TI  - Radioimmunoassays for spirapril and its active metabolite spiraprilate:
      performance and application.
AB  - Radioimmunoassays for a nonsulfhydryl angiotensin converting enzyme inhibitor
      prodrug--spirapril--and its active metabolite--spiraprilate--are described.
      Nonextraction equilibrium assays using antibodies with a high specificity for
      spirapril or spiraprilate were used, with charcoal separation of bound and free
      tracer. Within-assay reproducibility (CV%) was less than 20% in the concentration
      range 0.5-40 micrograms/L for both analytes and the comparable value for between
      assay reproducibility was less than 25%. Results for external quality control
      samples were in good agreement with the expected values of 0-250 micrograms/L
      (spirapril, r = 0.997) and 0-300 micrograms/L (spiraprilate, r = 0.999). Overall,
      samples circulated to four laboratories gave good agreement for measured values,
      including one center using gas chromatography-mass spectrometry analysis for the
      two compounds. Data are presented to show the suitability of these two assays to
      the measurement of spirapril and spiraprilate in clinical samples from assays to
      the measurement of spirapril and spiraprilate in clinical samples from dose
      ranging and bioequivalence studies. Results are also shown relating drug plasma
      concentration data to a measurement of the pharmacodynamic effects of
      spiraprilate, namely inhibition of angiotensin converting enzyme activity. It is
      concluded that these assays have the sensitivity for use in studies to model the
      relationship between the pharmacokinetics and pharmacodynamics of the two
      compounds.

PMID- 1384175
TI  - HLA epitope matching: a new way of evaluating an old matching system.

PMID- 1384177
TI  - In vitro genetics.
AB  - Understanding the basis of specificity in an intermolecular interaction is a
      common if difficult task; designing a specific intermolecular interaction is much
      more challenging. A new technique is described that has applications to both
      problems, at least with regard to nucleic acids. The power of this method lies in
      its ability to isolate extremely rare sequences with precisely specified
      properties from very large pools of random sequences.

PMID- 1384176
TI  - Landsteiner Award. HLA epitope matching.

PMID- 1384178
TI  - The 'ins' and 'outs' of mitochondrial membrane channels.
AB  - The outer membrane of the mitochondrion contains thousands of copies of a pore
      forming protein called VDAC or porin. Considerable progress has been made towards
      elucidating the molecular structure of this channel. Moreover, mounting evidence
      that the permeability of VDAC may be regulated is challenging the textbook notion
      of the outer membrane as a simple sieve. Numerous other channel activities have
      been detected by electrophysiol approaches in both the outer and inner
      mitochondrial membranes. The inner-membrane channels do not appear to be open
      under normal physiological conditions and so should not dissipate energy
      transducing ion gradients. The biological functions of the different classes of
      mitochondrial channels are uncertain, but several possibilities (including
      protein translocation) are being explored.

PMID- 1384179
TI  - Exploiting the chemical synthesis of RNA.
AB  - A number of nucleotide phosphoramidites are now available that permit the
      chemical synthesis of RNA, modified RNA and RNA-DNA chimeric oligonucleotides.
      Since the chemical strategy allows the introduction of a particular modification
      at any given site in a nucleotide polymer, very subtle and specific questions
      regarding structure-function relationships in RNA may be addressed.

PMID- 1384180
TI  - Induction of vascular adhesion molecules during rejection of human cardiac
      allografts.
AB  - Adhesion of leukocytes to vascular endothelium is a necessary step leading to the
      migration of cells into underlying tissues. Vascular adhesion molecules regulate
      this process and may play an important role in graft rejection.
      Immunocytochemical studies have been used to investigate the expression of
      vascular adhesion molecules (ICAM-1, PECAM, VCAM-1, and ELAM-1) in normal donor
      heart (n = 15) and myocardial biopsies from heart transplant patients with acute
      rejection (n = 15). Sections were also stained with antibodies against
      endothelium, leukocytes, MHC antigens, and markers of cell activation. In donor
      heart EN4, vWF, ICAM-1, PECAM, MHC class I--and, to a lesser extent, VCAM-1 and
      DR antigen--are expressed on arterioles and venules, whereas ELAM-1 and Pal-E are
      restricted to venules. Expression of Pal-E, VCAM-1, ICAM-1, and DR antigen was
      increased during rejection. Capillary endothelium normally expresses EN4, ICAM-1,
      PECAM, MHC class I, and DR antigen but little, if any, VCAM-1 or ELAM-1. During
      rejection, however, there is an increased expression of all adhesion molecules.
      This is paralleled by an increased expression of vWF by capillary endothelium. In
      addition, ICAM-1 like MHC class I antigen is induced on the myocardial membrane
      and intercalating discs. Endocardium from donor heart expresses EN4, vWF, PECAM,
      MHC class I, and sometimes Pal-E and ICAM-1, but very little VCAM-1, ELAM-1 or DR
      antigen. There is an increased expression of Pal-E, ICAM-1, VCAM-1, and DR
      antigen on endocardium from rejecting heart biopsies. Proliferating Ki-67+ cells
      and activated T cells expressing the receptor for IL-2 were also found in
      biopsies during rejection episodes.

PMID- 1384181
TI  - Comparison of DNA amplification and immunofluorescence for detecting Pneumocystis
      carinii in patients receiving immunosuppressive therapy.
AB  - Two studies were performed to compare the sensitivity of DNA amplification with
      immunofluorescence for the detection of Pneumocystis carinii in asymptomatic
      normal and immunosuppressed subjects receiving no anti-Pneumocystis
      chemoprophylaxis. In the first study, immunofluorescence and silver stains were
      used to examine 12 induced sputa and 12 bronchoalveolar lavage specimens from 24
      normal control subjects; induced sputa from 20 renal transplant recipients; and
      induced sputa from 11 patients with fibrosing alveolitis. All specimens were
      negative for P carinii using both stains, apart from one renal patient in whom 2
      P carinii cysts were seen by immunofluorescence alone. In the second study, DNA
      amplification and immunofluorescence were used to examine induced sputa from 3
      groups of 10 control, renal, and heart/lung transplant recipients. All 30
      specimens were negative for P carinii by immunofluorescence. However, 3 renal and
      2 heart/lung patients were positive for P carinii by DNA amplification alone. One
      of these patients developed P carinii pneumonia 6 weeks after sputum induction.
      DNA amplification is a more sensitive technique than immunofluorescence for
      detecting P carinii. P carinii colonization occurs in asymptomatic organ
      transplant recipients, but not in normal individuals.

PMID- 1384182
TI  - Evidence that the systematic analysis of bile cytology permits monitoring of
      hepatic allograft rejection.
AB  - Cytologic analysis was performed on 128 bile specimens collected by schedule from
      12 liver transplant recipients over a 4-month period. Clinical diagnoses at the
      time of specimen collection were determined retrospectively, as follows:
      clinically stable, 75; acute rejection, 15; CMV hepatitis, 1; systemic infection,
      8; ischemic injury, 24 (all within the first 4 days postop); nonclassifiable, 5.
      Bile analysis was done by a blinded investigator. Specimens contained ductal
      epithelial cells (EC) and inflammatory cells (IC), which were counted using
      Cytospin slide preparations. Greater than 10 cells/slide were seen in 93.3% of
      rejections, 91.7% of ischemic injuries, 100% of systemic infections, and 14.6% of
      stable patients. In samples collected after POD 4, IC were seen in 86.7% of
      rejections, yielding a specificity of 94.4% (P less than 0.001). If lymphoblastic
      cells were also seen, the specificity increased to 96.6%. Five specimens were
      obtained the day before the clinical diagnosis of rejection; all demonstrated IC.
      Seven specimens were obtained 3 days after beginning therapy for rejection. In 5
      the bile contained no IC, and clinical improvement occurred; in the 2 in whom IC
      were found, further therapy was subsequently required. IC were seen in 5 of 8
      specimens taken when systemic infection was present; the clinical setting allowed
      differentiation from rejection. Only 1 case of CMV hepatitis was included, thus
      no conclusions can be drawn for this entity. Cytoplasmic vacuolization of EC was
      observed in 30% of cases, in these, cyclosporine levels were significantly higher
      (989.9 +/- 356.9 vs. 672.8 +/- 421.2, P = 0.02). In summary, bile cytology
      analysis aides in the monitoring of the onset and duration of rejection. It may
      be an indicator of persistent rejection, and it may help prevent
      overimmunosuppression in those cases with normal cytological findings.

PMID- 1384183
TI  - Induction of transplantation tolerance in adults using donor antigen and anti-CD4
      monoclonal antibody.
AB  - The T-cell-mediated immune response usually results in the rapid destruction of
      organ allografts transplanted between murine strains incompatible for major and
      minor histocompatibility antigens. This response may be modified by pretreatment
      with either donor-specific antigen or anti-CD4 monoclonal antibody. Previous work
      by others has shown that combined treatment of mice with soluble protein antigens
      and anti-CD4 monoclonal antibody can produce antigen-specific B cell
      unresponsiveness that continues long after the nonspecific immunosuppressive
      effect of the mAb treatment has resolved. Following this principle we have shown
      that adult C3H/He mice can be made specifically unresponsive to vascularized
      C57BL/10 cardiac allografts by pretreating the recipient with donor alloantigen
      under the cover of a brief course of mAb against CD4. A full-dose response
      analysis shows that the dose of mAb is critically important for the successful
      induction of tolerance. Tolerance induction using this protocol is dependent on
      treatment with donor major histocompatibility complex antigens and occurs in the
      presence of marked depletion but not complete elimination of the CD4+ T cell
      subset. The unresponsiveness to alloantigen is antigen specific, as determined by
      the ineffectiveness of third-party (C57BL/10) alloantigen when combined with anti
      CD4 mAb to induce long-term survival of BALB/c allografts in C3H/He recipients.
      The tolerant state is specific and effective in the long-term as indicated by the
      specific acceptance of C57BL/10 skin grafts in recipients with surviving C57BL/10
      cardiac allografts. This study provides a simple method for the successful
      induction of specific transplantation tolerance in the adult across a full H-2
      major and minor antigen mismatch strain combination. The results illustrate the
      important role of the CD4 molecule in the T cell response to alloantigen in vivo
      and suggest possibilities for the therapeutic manipulation of complex immune
      reactions.

PMID- 1384184
TI  - Evidence that long-term cardiac allograft survival induced by anti-CD4 monoclonal
      antibody does not require depletion of CD4+ T cells.
AB  - Monoclonal antibodies that deplete cells carrying their target antigen are being
      used increasingly for immunosuppression in clinical and experimental
      transplantation. We have characterized a panel of rat antimouse CD4 monoclonal
      antibodies with the aim of establishing, in a vascularized organ transplant
      model, whether prolonged graft survival can be induced without recipient T cell
      depletion. The spatial relationship of the epitopes recognized by the anti-CD4
      mabs was established. Mabs of the IgG2b isotype were found to profoundly deplete
      CD4+ T cells in vivo, whereas IgG2a mabs did not. The IgG2b anti-CD4 mab YTS191
      and the IgG2a mab KT6 both blocked proliferation of C3H/He leukocytes in mixed
      leukocyte culture. Potent suppression of rejection and indefinite survival of
      cardiac allografts, mismatched for both major and multiple minor
      histocompatibility antigens (C57BL/10, H-2b into C3H/He, H-2k), was achieved with
      the IgG2b anti-CD4 mab YTS191 that depleted CD4+ T cells, (n = 9, median survival
      time (MST) greater than 100 days, P less than 0.001). The non-depleting IgG2a
      anti-CD4 mab, KT6, which had been shown to recognize and epitope on the CD4
      molecule closely related to that recognized by YTS191 and to block comparably in
      MLC, was also shown to be capable of producing long-term cardiac graft survival
      in this strain combination (n = 6, MST greater than 100 days P less than 0.001).
      The kinetics of the KT6 therapy on the blocking of the CD4 molecule in vivo were
      investigated and shown to correlate with the effectiveness of the mab in
      prolonging graft survival.

PMID- 1384185
TI  - Evidence that indefinite survival of small bowel allografts achieved by a brief
      course of cyclosporine or FK506 is not due to systemic hyporesponsiveness.
AB  - The immunological status of Lewis (LEW) recipients of indefinitely surviving
      (greater than 400 days) orthotopic Brown-Norway (BN) small bowel allografts was
      investigated 1 to 1 1/2 years after cessation of immunosuppressive therapy with
      either cyclosporine or FK506 and compared with recipients of syngeneic grafts. A
      normal proliferative response (as measured by a mixed lymphocyte culture) of
      recipient peripheral lymph node lymphocytes in response to the donor-specific
      (BN) and the third-party (ACI) antigen, was observed in all experimental groups.
      Cytolytic T cell generation (as measured by a standard 51Cr-release cytotoxicity
      assay) in response to the donor-specific (BN) and the third-party (ACI) antigen
      was observed also in all groups. A FACS analysis of allograft-recipient
      splenocytes showed no evidence for systemic lymphoid chimerism. BN or ACI skin
      grafts transplanted onto recipients of allogeneic and syngeneic small bowel
      grafts were rejected completely in 12-17 days, while the intestinal grafts
      remained functional. Immunohistologic evaluation of the allografts, using anti-BN
      class I and anti-Lewis class II monoclonal antibodies showed anti-BN staining on
      the epithelial and endothelial structures, whereas the mononuclear cells in the
      lamina propria stained positively with the anti-LEW monoclonal antibody. However,
      lymphoid depletion and scarring of Peyer's patches and mesenteric lymph nodes as
      well as focal obliterative mesenteric arteriopathy, indicative of an indolent
      chronic rejection, were observed. These data demonstrate that recipients of
      indefinitely surviving small bowel allografts remain immune competent and do not
      retain the intestinal graft on the basis of specific hyporesponsiveness to the
      donor antigens.

PMID- 1384186
TI  - The effects of immunosuppressive drugs on the regulation of activation-induced
      apoptotic cell death in thymocytes.
AB  - This study investigated the effects of immunosuppressive drugs on the regulation
      of thymocyte sensitivity to clonal deletion via programmed cell death, or
      apoptosis. We have previously shown that TcR/CD3 cross-linking and intracellular
      stimuli that mimic TcR/CD3 cross-linking induce apoptosis in many immature
      thymocytes in the presence, but not in the absence, of cyclosporine (CsA). We
      have interpreted those results to suggest that TcR/CD3-associated signals induce
      a CsA-sensitive mechanism that protects the cells from activation-induced
      apoptosis. In the present study, we compared the effects of CsA, FK506, and
      rapamycin (RAP) on the regulation of thymocyte apoptosis. Optimal concentrations
      of CsA and FK506 augmented apoptosis to similar levels. However, FK506 was
      approximately 100-fold more potent than CsA in thymocytes, which parallels the
      relative potencies of these drugs in inhibiting mitogen-induced proliferation of
      mature T cells. In contrast to CsA and FK506, RAP did not exhibit substantial
      apoptosis-augmenting activity. However, RAP interfered with the activity of
      FK506. This pattern mirrors that of RAP in TcR/CD3-mediated signaling pathways in
      mature T cells. Together these results provide evidence (1) that CsA, FK506, and
      RAP can act on immature thymocytes, (2) that the mechanisms by which the drugs
      affect mature and immature T cell responses are similar, and (3) that
      immunosuppressive drug therapy may affect not only mature peripheral T cells but
      also developing immature thymic T cells.

PMID- 1384187
TI  - Percutaneous biopsy of pancreas transplants.

PMID- 1384188
TI  - The salutary effect of FK506 in ischemia-reperfusion injury of the canine liver.
AB  - The present study was designed to elucidate the effect of FK506 on 90 min of warm
      ischemia of the liver and reperfusion in 30 dogs. Three groups of animals were
      studied. Group 1 animals received FK (0.15 mg/kg/day) for three days prior to the
      ischemia and group 2 animals got 2 ml of saline solution for three days instead
      of FK and were considered controls. In group 3 FK (0.15 mg/kg/day) was injected
      immediately upon reperfusion and two days thereafter. Evaluation of the
      effectiveness of the drug was monitored by measuring the serum activities of AST,
      ALT, LDH, serum total bilirubin, malondialdehyde, and by histopathological
      examinations of the liver specimens and survival of the animals for 7 days after
      reperfusion. The 7 day survival of the animals in group 1 (80%) was significantly
      (P < 0.05) improved compared with those in group 2 (30%) and group 3 (20%). The
      serum activities of AST, ALT, and LDH and total bilirubin were significantly
      lower in group 1 than in group 2 and group 3. FK pretreatment significantly
      prevented hepatocellular necrosis and neutrophilic infiltration in group 1 in
      comparison with those in group 2 and group 3. Although the malondialdehyde level
      in hepatic venous blood was relatively lower in group 1, this difference was not
      statistically significant. Three days FK pretreatment prevented hepatocellular
      injury and enzyme leakage after 90 min of hepatic ischemia, whereas FK treatment
      immediately upon reperfusion failed to do so. In conclusion, donor organ
      pretreatment with FK may become a promising strategy for improved allograft
      survival in liver transplantation.

PMID- 1384189
TI  - FK506-induced impairment of glucose metabolism in the primate--studies in
      pancreatic transplant recipients and in nontransplanted animals.
AB  - The effect of FK506 on glucose metabolism was studied in five cynomolgus monkeys
      after pancreatic transplantation and in 10 nontransplanted cynomolgus monkeys. We
      have clearly demonstrated that FK506 can induce hyperglycemia in these animals.
      In the orally treated nontransplanted animals the hyperglycemia was usually very
      mild (4.5-6.0 mmol/L). In one of the five transplanted animals, hyperglycemia was
      induced by the FK506 treatment, since histological signs of rejection were absent
      and since plasma glucose levels normalized on dose reduction. The glucose
      disappearance rates, as indicated by the K-values, decreased from a mean of 3.0
      +/- 0.5%/min before FK506 treatment to 2.4 +/- 0.6%/min at one month and 1.5 +/-
      0.4%/min at three months in the nontransplanted animals. In the transplant group,
      the K values decreased significantly from 4.2 +/- 0.6%/min in the donor animals
      to 1.4 +/- 0.4%/min at day 10 posttransplantation (P < 0.02). At one and three
      months postoperatively, the mean K-values were 1.4 +/- 0.2%/min and 1.2 +/-
      0.6%/min, respectively. We conclude that FK506 is diabetogenic in the cynomolgus
      monkey. This side effect, however, was found to be reversible on dose reduction.

PMID- 1384190
TI  - The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil
      conjugate (KM2210) and its beneficial effect on allogeneic bone marrow
      transplantation in mice.
AB  - KM2210, a conjugate of estradiol and chlorambucil (CBL), which was originally
      developed as an anti-breast cancer agent, inhibits proliferative response of
      human mononuclear cells to alloantigens in mixed lymphocyte culture in a dose
      dependent manner, but has no effect on their response to phytohemagglutinin.
      Neither estradiol benzoate nor CBL alone showed these unique actions. The
      suppressive effect of KM2210 on MLC was abrogated by adding of anti-transforming
      growth factor-beta (TGF-beta) antibody to the culture, but was not affected by
      the addition of interleukin-2, suggesting that KM2210, unlike CBL, displays its
      actions via TGF-beta. In experimental allogeneic bone marrow transplantation
      using mice, daily oral administration of KM2210 (2 mg/kg/day) for 30 days
      posttransplant significantly inhibited the alloantigen-specific immune reactions.
      Furthermore, the survival rate of the KM2210-treated mice was significantly
      higher than that of the cyclosporine-treated (2 mg/kg/day, p.o.) mice, and no
      adverse effect of KM2210 on hematopoietic recovery was found. These results
      strongly suggest possible clinical benefits of KM2210 as a new immunosuppressive
      agent for the prevention and treatment of graft-versus-host disease and other
      allospecific immune reactions.

PMID- 1384191
TI  - Reduction of leukocyte adherence and emigration by cyclosporine and L683,590
      (FK506) in postcapillary venules.
AB  - Although the actions of immunosuppressive agents on lymphocytes are well
      characterized, their influence on leukocyte-endothelial cell adhesive
      interactions has not been defined. The objective of this study was to determine
      whether cyclosporine and L-683,590 (FK520) could modify the adhesion and
      emigration of leukocytes in postcapillary venules that are exposed to
      inflammatory mediators such as platelet activating factor (PAF) and leukotriene
      B4 (LTB4). The rat mesentery was prepared for in vivo microscopic observation.
      Venules with internal diameters ranging between 25 microns and 35 microns were
      selected for study. Erythrocyte velocity, vessel diameter, leukocyte rolling
      velocity, and the number of adherent (stationary for > 30 sec) and emigrated
      leukocytes were measured during superfusion of the mesentery with bicarbonate
      buffered saline. Repeat measurements of adhesive and hemodynamic parameters were
      obtained between 50 and 60 min of superfusion with either 100 nM PAF or 20 nM
      LTB4 added to bicarbonate-buffered saline. In some experiments, animals were
      treated with either cyclosporine or L-683,590. Both PAF and LTB4 caused increases
      in leukocyte adherence and emigration, and reductions in leukocyte rolling
      velocity and venular shear rate. Cyclosporine prevented all of the adhesive and
      hemodynamic alterations induced by PAF, but not LTB4. L-683,590 was effective in
      preventing the responses elicited by both PAF and LTB4. These results indicate
      that modulation of leukocyte-endothelial cell adhesive interactions may represent
      a novel mechanism of action for cyclosporine and L-683,590.

PMID- 1384192
TI  - Recurrence of hepatitis C virus infection after orthotopic liver transplantation.

PMID- 1384193
TI  - Lineage in the cerebral cortex: when is a clone not a clone?

PMID- 1384194
TI  - Leucocyte recruitment and inflammation in the CNS.

PMID- 1384195
TI  - Programmed cell death: the paths to suicide.

PMID- 1384196
TI  - Role of the central auditory system in hearing: the new direction.
AB  - The mammalian central auditory system contains a large number of subcortical
      auditory nuclei, which were once thought to form a simple relay system, taking
      signals from the ear to the cortex where all information processing would have
      occurred. Now it appears that these subcortical nuclei are themselves responsible
      for the extraction and analysis of the dimensions of sounds. Not only do the
      nuclei encode dimensions defining the nature of the sound, but also they extract
      features of sound location. Three major nuclei in the superior olivary complex of
      mammals extract the horizontal direction of a sound source, and it seems likely
      that other nuclei in the auditory system encode elevation and distance. This
      shift in viewpoint away from the attributes of sound to the attributes of sound
      sources is an important new step in the investigation of the role of the central
      auditory system in hearing.

PMID- 1384197
TI  - Neural lesioning with ribosome-inactivating proteins: suicide transport and
      immunolesioning.
AB  - Toxic lectins, plant proteins that inactivate ribosomes, irreversibly inhibit
      protein synthesis with high efficiency. After intraneural (subepineurial)
      microinjection, these agents are taken up by axons and are retrogradely
      transported to the perikarya, where they result in cell death. These 'suicide
      transport' toxins can produce pathway-specific lesions that are useful in several
      types of experiment, including cellular localization of neurotransmitter
      receptors. The toxins can be coupled to monoclonal antibodies to produce
      immunotoxins: reagents that can make highly selective lesions of specific types
      of neurons. Central or peripheral neurons that express the low-affinity NGF
      receptor are selectively destroyed by the immunotoxin 192 IgG-saporin.
      Development of other anti-neuronal immunotoxins should provide a variety of
      powerful selective lesioning tools.

PMID- 1384198
TI  - G-protein cascades: gain and kinetics.
AB  - G-protein cascades provide amplification in a wide variety of biological signal
      transducers--from hormonal and synaptic systems to the receptor cells of vision
      and olfaction. Through recent understanding of the molecular mechanisms involved,
      it is possible to construct a quantitative description of the amplification and
      speed of response of the cascade. The gain and kinetics can now be described in
      terms of physical parameters, such as enzyme activities and the densities and
      lateral diffusion coefficients of the proteins involved.

PMID- 1384199
TI  - Spatial memory and adaptive specialization of the hippocampus.
AB  - The hippocampus plays an important role in spatial memory and spatial cognition
      in birds and mammals. Natural selection, sexual selection and artificial
      selection have resulted in an increase in the size of the hippocampus in a
      remarkably diverse group of animals that rely on spatial abilities to solve
      ecologically important problems. Food-storing birds remember the locations of
      large numbers of scattered caches. Polygynous male voles traverse large home
      ranges in search of mates. Kangaroo rats both cache food and exhibit a sex
      difference in home range size. In all of these species, an increase in the size
      of the hippocampus is associated with superior spatial ability. Artificial
      selection for homing ability has produced a comparable increase in the size of
      the hippocampus in homing pigeons, compared with other strains of domestic
      pigeon. Despite differences among these animals in their histories of selection
      and the genetic backgrounds on which selection has acted, there is a common
      relationship between relative hippocampal size and spatial ability.

PMID- 1384200
TI  - Calcium-binding proteins in the nervous system.
AB  - Among the many calcium-binding proteins in the nervous system, parvalbumin,
      calbindin-D28K and calretinin are particularly striking in their abundance and in
      the specificity of their distribution. They can be found in different subsets of
      neurons in many brain regions. Although it is not yet known whether they play a
      'triggering' role like calmodulin, or merely act as buffers to modulate cytosolic
      calcium transients, they are valuable markers of neuronal subpopulations for
      anatomical and developmental studies.

PMID- 1384201
TI  - Continuous infusion of angiopeptin significantly reduces accelerated graft vessel
      disease induced by FK 506 in a rat heart allograft model.

PMID- 1384202
TI  - Prevalence of hepatitis C virus in a group of kidney transplant patients in
      Mexico.

PMID- 1384203
TI  - Antibodies to hepatitis C virus in Omani patients with renal disease.

PMID- 1384204
TI  - Molecular markers of liver damage in liver transplantation: effect of rapid
      cooling on the expression of hepatic genes.

PMID- 1384205
TI  - Effect of FK 506 and cyclosporine A on hepatic energy status in the rat after
      warm ischemia, as monitored by 31P nuclear magnetic resonance spectroscopy in
      vivo.

PMID- 1384206
TI  - T-cell antigen receptor V alpha gene expression in rejecting renal allografts.

PMID- 1384207
TI  - Hepatitis C infection in liver transplant patients.

PMID- 1384209
TI  - FK 506 in canine renal transplantation.

PMID- 1384208
TI  - Effective organ preservation with modified HES-free UW solution with lowered
      potassium content.

PMID- 1384210
TI  - Effects of in vitro hyperthermia on the expression of adhesion molecules in
      cytokine-stimulated human umbilical vein endothelial cells.

PMID- 1384211
TI  - Amiloride: a molecular probe for mechanosensitive channels.

PMID- 1384212
TI  - Direct regulation of cardiac Ca2+ channels by G proteins: neither proven nor
      necessary?
AB  - The cardiac L-type Ca2+ channel has served as a model for ion channel regulation
      for over a decade. The Ca2+ current is increased by beta-adrenoceptor stimulation
      and this effect is inhibited by muscarinic acetylcholine receptor stimulation. It
      is well established that beta-adrenoceptor stimulation increases this current
      largely by cAMP-dependent phosphorylation but recently data have been presented
      that suggest that this channel may also be regulated directly by G proteins. This
      review by Criss Hartzell and Rodolphe Fischmeister evaluates evidence for this
      second regulatory pathway and concludes that, although G proteins affect cardiac
      Ca2+ channels in bilayers and excised patches, there is little evidence that this
      pathway is physiologically significant.

PMID- 1384213
TI  - New mutants to explore nicotinic receptor functions.

PMID- 1384214
TI  - Galanin and galanin antagonists: molecular and biochemical perspectives.
AB  - The neuropeptide galanin potently inhibits insulin release, hippocampal
      acetylcholine release and firing of locus coeruleus cells, and stimulates feeding
      and release of growth hormone. Galanin regulates K+ channels, adenylyl cyclase
      and phospholipase C by acting at Gi/Go protein-coupled high-affinity receptors.
      Galanin receptor agonists such as the N-terminal fragment galanin1-16 act
      synergistically with morphine in the somatosensory system and have potential
      analgetic application. Galanin antagonists may be useful therapeutic agents in
      endocrinology, neurology and psychiatry. The enhancing effect of such agents on
      hippocampal cholinergic function would be useful in treatment of Alzheimer's
      disease. Recent synthesis of a series of high-affinity galanin antagonists,
      reviewed, along with galanin's actions, by Tamas Bartfai and colleagues, opens
      the possibility of examining the functions of endogenous galanin and test the
      pharmacological usefulness of antagonism of galanin function in the endocrine,
      somatosensory and central nervous systems.

PMID- 1384215
TI  - [Loop ileostomy--the first choice for relief of colon and rectum].
AB  - In numerous comparative investigations, loop-ileostomy has proved superior to
      transversostomy. The operative technique is described and experience from 27 loop
      ileostomies carried out in a department for organ surgery are reviewed. The
      qualities of the method as compared with transversostomy are discussed on the
      basis of the literature and the authors' own results. It is concluded that loop
      ileostomy may, in general, be preferred for temporary and palliative relief of
      the colon.

PMID- 1384216
TI  - [Diagnosis and therapy of metastasis-induced pathologic fractures].
AB  - Improved survival rates of cancer patients have led to an increase in the
      incidence of metastatic disease of the bone. Normal load and minimal trauma may
      result in pathological fractures. The malignant diseases most commonly diagnosed
      were breast cancer, bronchial carcinoma and hypernephroma. The majority of the
      patients treated were female. The average interval observed between diagnosis of
      primary malignant disease and occurrence of the pathological fracture was 2.8
      years. The purpose of the surgical procedure is to achieve immediate and lasting
      stability and ultimately to increase and restore the quality of life. Immediate
      postoperative mobilization and early functional treatment are an indispensable
      part of the management of pathologic fractures. If possible extensive bone
      destructions involving the risk of fracture should be stabilized
      prophylactically. Specific techniques of composite osteosyntheses of fractures in
      metastatic disease of the bone are presented.

PMID- 1384217
TI  - [The effect of renal artery embolization on the results of treating kidney cancer
      patients].
AB  - To analyze the prognosis, 401 renal cancer cases were examined retrospectively
      and prospectively. There were 157 females and 244 males. Preoperative
      embolization of the renal artery resulted in longer survival: in stage T3 it
      increased from 44 to 60%, in stage T4 from 7 to 50%. After palliative nephrectomy
      the patients' mean survival reached 10.6 months against 16 months following
      palliative embolization of the kidney. Palliative embolization is thought the
      most effective intervention in inoperable cases of renal carcinoma.

PMID- 1384218
TI  - Temperature steering in prostate by simultaneous transurethral and transrectal
      hyperthermia.
AB  - Localized hyperthermia (HT) is presently under investigation as a treatment for
      benign prostatic hyperplasia and carcinoma of the prostate (CaP). One popular
      approach employs a transrectal (TR) device, a directional microwave (MW)
      applicator inserted into the rectum and aimed at the prostate. Alternatively, in
      the transurethral (TU) technique, a symmetrically radiating MW antenna is placed
      directly within the prostatic urethra. Used individually, TR applicators are
      capable of effectively heating (> 42 degrees C) the prostate up to 2 cm from the
      rectum, whereas TU applicators selectively heat the periurethral tissue with
      effective radial penetration of about 0.6 cm. Neither technique is of much value
      in heating the anterior prostate. In general, the highest temperatures are
      produced in the tissue immediately adjacent to the surface of intracavitary
      microwave devices. However, when MW antennas are used in arrays, the resulting
      heating pattern can differ significantly from that of the individual antennas.
      Heating at depth can be selectively enhanced and "steered" by adjusting the phase
      relationship between the devices. Prostatic temperature profiles were measured in
      6 patients treated with TR alone, TU alone, and simultaneous TR and TU heating.
      In the combined treatments different phase relationships between the antennas
      were applied. We found that a higher temperature could be produced in the center
      of the prostate than on the surface of either applicator for certain phase
      relationships, and that the temperature profiles could be changed by shifting
      phase. The results of these measurements are in agreement with those of a
      computer simulation. Based on the above data we feel the combined use of TU and
      TR hyperthermia may be justified in Phase I-II trials for patients with locally
      advanced CaP.

PMID- 1384219
TI  - Local staging of prostate cancer by tumor volume, prostate-specific antigen, and
      transrectal ultrasound.
AB  - Conventional methods of staging prostate tumors are highly inaccurate. To improve
      clinical staging, prostate-specific antigen (PSA) levels (> 10 ng/mL),
      sonographic tumor volume (> 3 cc), maximum tumor diameter, length of capsular
      tumor abutment, and overall impression of capsular irregularity suggesting
      periprostatic tumor spread were assessed in 29 men prior to undergoing radical
      prostatectomy for clinically localized tumor. After surgery, 18 men had tumor
      confined to the prostate, while 11 men had histologic evidence of extracapsular
      disease. Analysis of the parameters measured showed these were the most helpful
      factors in predicting the presence of extracapsular disease. However, the
      positive and negative predictive values were only 70 to 90 percent. Therefore,
      the clinical usefulness of any one measurement alone in determining treatment for
      the individual patient is limited. However, combining these parameters yields an
      improved prediction of extracapsular disease. All 6 patients with PSA < 10 ng/mL,
      tumor volume < 3 cc, and no capsular irregularity on ultrasound had localized
      disease (neg. predictive value = 100%), while all 7 patients who had more than
      one of these parameters had extracapsular disease (pos. predictive value = 100%).
      Thus, using the factors in combination may provide more accurate staging and
      thereby help in counseling patients regarding therapy.

PMID- 1384220
TI  - Relationship of response to transurethral hyperthermia and prostate volume in BPH
      patients.
AB  - A response to transurethral microwave hyperthermia (TUHT) at 915 MHz and its
      relationship to prostate volume was examined in 63 poor surgical risk benign
      prostatic hyperplasia (BPH) patients. All patients had moderate-to-severe
      obstructive signs and symptoms, and received > or = 5 TUHT one-hour sessions.
      Treatment temperature was controlled on the urethral surface at 45 degrees C +/-
      1 degree C. Follow-up ranged from twelve to forty-four months (mean 18 months).
      The mean prostate volume was 57 cc (range 10-301 cc). There were 40 patients
      (63%) with prostate volume < or = 50 cc and 23 (37%) with a volume > 50 cc.
      Treatment failure was seen in 6 patients (10%). It was 10 percent in 40 patients
      with smaller glands and 9 percent for those 23 with larger prostates, N.S. at p =
      0.49. Subjective treatment response was seen in 58 patients (92%). It was 90
      percent for the 40 patients with < or = 50 cc prostates vs. 96 percent for the 23
      with > 50 cc prostates, N.S. at p = 0.75. This study suggests that the initial
      prostate volume is not an important parameter predicting response to TUHT.

PMID- 1384221
TI  - Distribution of cytokeratins, vimentin and desmoplakins in normal renal tissue,
      renal cell carcinomas and oncocytoma as revealed by immunofluorescence
      microscopy.
AB  - Forty-two renal cell carcinomas, one oncocytoma and normal renal tissue were
      studied for the presence of cytokeratins and vimentin. The investigations were
      performed by immunofluorescence microscopy applying a panel of mono- and
      polyclonal antibodies to intermediate filament proteins. In all tumours except
      chromophobic renal cell carcinoma (CRCC) and oncocytoma a co-expression of
      cytokeratins and vimentin could be shown. The intermediate filament expression
      was often, however, very heterogeneous particularly with respect to the
      distribution of cytokeratins and vimentin, to the clonality of the antibodies
      used and to the tumour areas studied. The latter could be impressively
      demonstrated by examining a whole tumour. In CRCC and oncocytoma all tumour cells
      expressed cytokeratins and, in addition, single tumour cells also expressed
      vimentin. In normal renal tissue we could show vimentin-positive epithelia of
      proximal and distal tubules, which is reported for the first time.

PMID- 1384222
TI  - Tenascin in salivary gland tumours.
AB  - The distribution of tenascin immunoreactivity was analysed in salivary gland
      tissue and in various benign and malignant tumours of the salivary gland. In the
      non-neoplastic tissue, tenascin was seen in the areas of basement membranes of
      the ductal epithelium. No immunoreactivity could be observed in the serous or
      mucous glands. In pleomorphic adenomas, tenascin immunoreactivity could be seen
      in the stromal compartment. It was more pronounced in the dense stromal areas and
      chondroid elements than in the myxoid area. In Warthin's tumours, strong tenascin
      immunoreactivity could be observed in the basement membrane zone of the
      epithelial component. In the lymphatic component, faint reticular staining could
      be seen. In adenoid cystic carcinomas, acinic cell tumours and mucoepidermoid
      carcinomas, tenascin showed a linear stromal distribution. No intracytoplasmic
      immunoreactivity could be seen in any of the cases. The widespread tenascin
      positivity in salivary gland tumours suggests that tenascin may play a role in
      the induction and progression of salivary gland tumours, presumably by
      interfering with the normal parenchymal-mesenchymal interaction.

PMID- 1384223
TI  - Small cell carcinoma of the ovary: an immunohistochemical and ultrastructural
      study with a review of the literature.
AB  - This is an immunohistochemical and ultrastructural study of two small cell
      carcinomas of the ovary with a review of the literature. These cases showed a
      dimorphic population of small and large cells sharply demarcated from each other.
      Cytokeratin 18 and vimentin were mainly expressed in the large tumour cells, some
      of which also stained for alpha-smooth muscle actin. Periodic-acid-Schiff
      positive, alpha-1-antitrypsin-positive hyaline globules were present in one case.
      Ultrastructural findings included filamentous nucleolonema as well as evidence of
      smooth muscle differentiation. Some of these observations have not been
      previously reported. Certain of the above features seem to support a germ cell
      origin of small cell carcinoma, but they cannot be considered specific for germ
      cell neoplasms. Thus, small cell carcinoma of the ovary cannot be classified into
      one of the known categories of ovarian tumours at the present time.

PMID- 1384224
TI  - Nodular sclerosing Hodgkin's disease and large cell lymphoma. Immunophenotypic
      characterization of a composite case.
AB  - Composite lymphomas have rarely been reported in Hodgkin's disease (HD), except
      in the lymphocyte predominance sub-type, and immunohistochemical investigations
      have been performed in only few cases. We describe the histological and
      immunophenotypical findings in a case of composite nodular sclerosing HD and high
      grade, large cell non-Hodgkin's lymphoma (NHL). In our case HD and NHL cells
      displayed striking morphological and immunophenotypical divergence, suggesting a
      lack of correlation between the two neoplasms.

PMID- 1384226
TI  - An immunohistochemical study of the breast using antibodies to basal and luminal
      keratins, alpha-smooth muscle actin, vimentin, collagen IV and laminin. Part I:
      Normal breast and benign proliferative lesions.
AB  - The distribution of simple epithelial (K8/18/19) and basal (myoepithelial)
      (K5/14) keratins, alpha-smooth-muscle actin, vimentin, collagen IV and laminin in
      normal mammary glands and in benign proliferative lesions was studied using
      monoclonal antibodies (mAbs). These antibodies (Abs) identified myoepithelial
      cells and luminal cells specifically. In lesions with adenosis and papillomas,
      the two-layered formation resembled that of normal glands with a purely
      myoepithelial-epithelial differentiation. In scleradenotic lesions, the main cell
      was of myoepithelial immunophenotype with intermixed trabecular-tubular
      proliferations of simple-type epithelium. The sclerosis seems to be the result of
      an irregular basal lamina synthesis by the myoepithelial cells. In contrast to
      these lesions, epitheliosis represents a purely intraluminal cell proliferation
      of clearly simple epithelial immunophenotype and of cells with a basal keratin
      phenotype, lacking myoepithelial differentiation antigen actin. The basal keratin
      type epithelium may represent post-stem or intermediate cells developing into
      luminal epithelium. Epitheliosis appears to be a purely epithelial hyperplasia
      with striking similarity to the regeneration of normal breast epithelium. The
      different proliferative patterns may give an explanation for differences in
      potential cancer risks of patients with these lesions.

PMID- 1384225
TI  - Venular endothelium binding molecules CD44 and LECAM-1 in normal and malignant B
      cell populations. A comparative study.
AB  - Lymphocytes leave the blood via post-capillary venules by binding initially to
      their specialized endothelium. CD44 is a 80-90 kDa hyaluronate-binding
      glycoprotein involved in binding to endothelium of high endothelial venules
      (HEV). LECAM-1 is a 75-85 kDa glycoprotein with lectin activity interacting with
      human peripheral lymph node vascular addressin (PNAd) on HEV. This
      immunohistochemical study shows that CD44 and LECAM-1 are essentially
      coordinately expressed on B-lymphocytes. The mode and level of CD44/LECAM-1
      expression dissect the peripheral B-cell development into stages that are closely
      linked to morphologically defined B-cell compartments. Although statistically
      correlated in B-cell leukaemias (p < 0.0009) and extranodal B-cell lymphomas (p <
      0.003), expression of both molecules was less stringently coordinated in 127 B
      cell neoplasms examined. B-cell chronic lymphocytic leukaemia, hairy cell
      leukaemia and mantle zone lymphoma were CD44/LECAM-1 positive, thus corresponding
      to their reactive counterparts. Correspondingly, follicular centre cell-derived
      lymphomas were devoid of both markers. Conversely, CD44 and LEC-AM-1 were
      infrequently detectable in extranodal malignant B-cell neoplasms, irrespective of
      their maturational state. Presence versus absence of CD44 and LECAM-1, alone or
      together, determined neither the leukaemic versus aleukaemic state nor the nodal
      versus extranodal tumour-forming phenotype of a B-cell tumour.

PMID- 1384227
TI  - An immunohistochemical study of the breast using antibodies to basal and luminal
      keratins, alpha-smooth muscle actin, vimentin, collagen IV and laminin. Part II:
      Epitheliosis and ductal carcinoma in situ.
AB  - A detailed immunohistochemical study has been carried out on 63 breast lesions
      with epitheliosis, ductal carcinoma in situ and clinging carcinoma (lobular
      cancerization), using antibodies directed against keratins 5/14 and 14, 15, 16,
      18, 19, vimentin, smooth muscle actin, collagen IV and laminin. The results have
      shown that epitheliosis on the one hand and ductal in situ and clinging carcinoma
      on the other are immunohistochemically different epithelial lesions. Epitheliosis
      appears to be epithelial hyperplasia with keratin 5/14 and keratin 14, 15, 16,
      18, 19-positive cells. Compared to epitheliotic cells tumor cells of clinging
      carcinoma, lobular cancerization and ductal carcinoma in situ expressed only
      luminal keratins 14, 15, 16, 18, 19 in 85% of the cases studied; whereas in 15%
      there was a basal keratin expression. From our results we conclude that the
      clinging carcinoma (lobular cancerization) represents the initial morphological
      step in the development of ductal carcinoma in situ and thus may be interpreted
      as a minimal ductal neoplasia. With the immunohistochemical demonstration of
      basal and luminal keratins it may be possible in individual cases to
      differentiate between benign and malignant in situ lesions of the breast.

PMID- 1384229
TI  - Interferon induction of chicken MHC class I gene expression: phylogenetic
      conservation of the interferon-responsive element.
AB  - The 5' upstream region of a chicken MHC class I gene BF-IV contains sequence
      motifs similar to the interferon consensus sequences (ICS) contained in promoters
      of many mammalian interferon-regulated genes. To study a possible functional role
      of this putative chicken ICS, an oligonucleotide spanning the upstream sequences
      of the BF-IV gene (-174/-194) was cloned singly or in multiple copies before the
      herpes TK promoter controlling the chloramphenicol acetyl transferase (CAT) gene
      (pBLCAT2). Transient expression studies performed with primary chicken
      fibroblasts (CEF) showed that the chicken ICS represses constitutive promoter
      activity. The chicken ICS, however, enhanced CAT activity up to 20-fold following
      treatment with chicken interferon (IFN). Deletion analysis of the BF-IV promoter
      also confirms that the upstream DNA sequences (-174/-194) contain a functional
      ICS recognized by chicken interferon. The murine ICS of the H2-Ld gene was also
      activated by chicken interferon when introduced into CEF. IFN activation of
      chicken ICS containing reporters was also observed in transformed chicken
      fibroblast lines. We show that the chicken ICS binds two specific nuclear factors
      present in chicken fibroblasts which are induced by interferon. These factors
      were also capable of recognizing the mouse ICS, suggesting the conservation of a
      relevant DNA-binding protein. Taken together, these data indicate that the
      chicken ICS motif contained in a sequence from -174 to -194 of the BF-IV gene
      acts as a strong interferon-response element, which has been functionally
      conserved during about 270 million years of separate evolution of mammals and
      birds.

PMID- 1384228
TI  - Chondroblastoma of bone. A clinical, radiological, light and immunohistochemical
      study.
AB  - The clinical and morphological findings of 53 chondroblastomas in the files of
      the Bone Tumour Registry of Westphalia are presented. The mean age of all
      patients was 19.2 years. The male-to-female ratio was 1.5:1. Forty-two of the
      tumours (79.8%) were located in the long tubular bones and short tubular bones of
      the hands and were closely related to the growth plate. Six cases (11.3%) were
      found in the flat bones, 4 cases (7.5%) in the tarsal bones and 1 case (1.9%) in
      the craniofacial bones. The characteristic radiological feature of 44
      investigated lesions was a mostly eccentric radiolucency with a geographic
      pattern of bone destruction and matrix calcifications. Periosteal reaction was
      evident in 9% of the cases. Most tumours demonstrate the typical morphological
      features of chondroblastoma, but 3 cases resembled a giant cell tumour. In 2
      cases a haemangiopericytoma-like growth pattern was observed. Nine of the tumours
      had an aneurysmal bone cyst-like component. Vascular invasion was seen in 1 case.
      Immunohistochemically most cells in 30 of the cases and fetal chondroblasts in 3
      cases were strongly positive with vimentin and S-100 protein. Collagen type II
      was positive in the chondroid matrix of the tumours and in fetal cartilage
      tissue; collagen type VI was present focally around individual tumour cells and
      was always seen in the chondroid matrix of the lesions and in fetal cartilage.
      These findings support the cartilaginous nature of these tumours. In paraffin
      sections, 46.6% of the cases revealed a distinct positive reaction of some tumour
      cells with the monoclonal cytokeratin antibody KL1 (molecular weight 55-57 kDa).
      Only 4 of them demonstrated a coexpression with the other monoclonal cytokeratin
      antibody CK (clone MNF 116, molecular weight 45-56.5 kDa). In paraffin sections
      all fetal chondroblasts were negative with both cytokeratin antibodies. Frozen
      sections of 3 tumours showed a strong positive reaction with both cytokeratin
      antibodies in many chondroblasts, indicating an "aberrant" cytokeratin
      expression. Osteoclast-like giant cells stained positive with leucocyte-common
      antigen (LCA) and with the macrophage-associated antibody KP1, but were negative
      with the other macrophage-associated antibody MAC 387. Recurrence rate was 10.7%.
      The clinical course of all tumours was benign.

PMID- 1384230
TI  - Production and characterization of monoclonal antibodies to porcine group C
      rotaviruses cross-reactive with group A rotaviruses.
AB  - Five monoclonal antibodies (MAbs) to porcine group (gp) C rotaviruses (Cowden and
      Ah strains) reactive with both gp A and C rotaviruses in cell culture
      immunofluorescence (CCIF) tests were produced and characterized. These MAbs
      reacted with three strains of gp A and two strains of gp C rotaviruses in a CCIF
      test and were classified into two groups based on their CCIF titers. The MAbs
      also reacted to various degrees with cell-culture-propagated porcine gp C
      rotavirus (Cowden) and bovine gp A rotavirus (NCDV) in an enzyme-linked
      immunosorbent assay by using the MAbs as capture antibodies. Fecal samples
      containing human, bovine, and porcine strains of gp A and C rotaviruses were
      positive when tested using one of the MAbs in this assay. The MAbs recognized VP6
      of gp A rotavirus and the VP6 counterpart (41-kDa protein) of gp C rotavirus in a
      Western blot assay. Results of competitive binding assays on four MAbs indicated
      that gp A and gp C rotaviruses share three overlapping epitopes within a single
      antigenic domain. These results suggest that gp A and C rotaviruses share a
      common antigen located on the VP6 protein, which is recognized by certain MAbs in
      various serologic assays.

PMID- 1384231
TI  - Analysis of epitopes on potato leafroll virus capsid protein.
AB  - Pepscan hexapeptides prepared to the capsid protein amino acid sequence of potato
      leafroll luteovirus (PLRV) were tested against both polyclonal and monoclonal
      antibodies. Twelve continuous epitopes were identified: 11 were detected by two
      different PLRV polyclonal antisera, but only 4 were detected by both antisera.
      The 12th epitope reacted with monoclonal antibody BG3. The location of most of
      the epitopes did not correlate well with antigenic areas predicted by computer
      algorithms. Comparison of the amino acid sequences of PLRV and southern bean
      mosaic virus capsid proteins allowed a preliminary assignment of epitopes 4-12 to
      different regions of the putative S domain of the PLRV subunit. Five out of 14
      monoclonal antibodies and both of the polyclonal antisera reacted with epitope 1
      at the N-terminus. ELISA data indicated that even though the N-terminus is
      hydrophobic, it is exposed at the surface of the particles.

PMID- 1384233
TI  - Detailed diagnoses and procedures, national hospital discharge survey, 1990.
AB  - This report presents statistics on conditions diagnosed and surgical and
      nonsurgical procedures performed in non-federal short-stay hospitals. The
      statistics are based on data collected through the National Hospital Discharge
      Survey from a national sample of the hospital records of discharged inpatients.
      Estimates of first-listed diagnoses, all-listed diagnoses, days of care for first
      listed diagnoses, and all-listed procedures are shown by sex and age of patient
      and geographic region of hospital.

PMID- 1384232
TI  - Human oocytes express murine retroviral equivalents.
AB  - Unfertilized human oocytes expressed a gp70-related epitope as observed when
      staining section immunocytochemically with a panel of monoclonal antibodies
      against gp70 of murine leukemia virus. Some oocytes also expressed virus-like
      particles at the cell membrane. Follicular fluids, corresponding to these
      oocytes, contained p30- and gp70-related antigens, reverse transcriptase, and an
      increased titer of interferon. The three- to four-cell human cleavage stages did
      not contain the gp70-related epitope. It is concluded that human oocytes, but not
      early cleavage stages, express products that suggest the presence of an active
      endogenous retrovirus genome.

PMID- 1384236
TI  - Second-generation anti-HCV tests predict infectivity.
AB  - Twenty-four blood donors found positive for the first-generation hepatitis C
      antibody (anti-HCV) test (Ortho EIA-I) and 88 of their recipients over the period
      from 1972 to 1990 were retrospectively investigated with different first- and
      second-generation anti-HCV tests. The aim of the study was to identify the
      infective donors and to evaluate the tests. Seven donors, who probably were
      infective carriers of HCV, were also second-generation test (EIA-II) positive,
      compared to only 3 out of 17 noninfective donors. Among the infected recipients,
      14 out of 29 (48%) were positive for the second-generation test only. The second
      generation test identified the infective donors in our study and was more
      sensitive than the first-generation test. We therefore recommend that blood
      donors are screened with EIA-II. Positive test results should be confirmed by the
      recombinant immunoblot assay (RIBA-II), and persons with positive or not
      conclusive RIBA-II should not be accepted as blood donors.

PMID- 1384235
TI  - [Antifibrosis effect of modified forms of catalase and superoxide dismutase in
      experimental silicosis].
AB  - The forms of catalase modified by treatment with dextran aldehyde were obtained
      and studied. Efficacy of the preparations containing native and modified forms of
      catalase and superoxide dismutase as well as their covalent bienzyme conjugate
      containing catalase-dextran aldehyde-superoxide dismutase was studied in rats
      with simulated silicosis. The preparations were administered into rats by means
      of inhalation and intraperitoneal injection. Positive protective effect exhibited
      a mixture of native enzymes and their covalent conjugate. The most pronounced
      additional effect was caused by the mixture of native catalase and superoxide
      dismutase as compared with modified preparation of superoxide dismutase. The
      preparation of bienzyme containing conjugate was less effective.

PMID- 1384234
TI  - [The hemodynamic disorders in Sudeck's atrophy and the effect on them of
      interference therapy].
AB  - Interferential currents applied to the forearm fracture region of 80 patients
      with Sudeck atrophy eliminated hemodynamic changes in the affected limb as shown
      by capillaroscopy, rheovasography. The effect of the treatment is attributed to
      recovery of normal blood flow and microcirculation in the region of bone atrophy
      as well as analgetic action of pulse current.

PMID- 1384237
TI  - Hepatitis C virus antibody in Kuwait.

PMID- 1384238
TI  - [The characteristics of human immunodeficiency virus strains isolated from HIV
      infected persons on the territory of the USSR].
AB  - Fifty-seven HIV-1 strains were isolated from peripheral blood lymphocytes of 102
      HIV-infected persons involved in epidemic outbreaks in different cities of the
      USSR. The effectiveness of isolation was 29.1% in asymptomatic infection, 51.7%
      in cases with generalized lymphadenopathy, and 82.6% in persons with severe
      clinical manifestations. Identification of the isolates by indirect
      immunofluorescence, ELISA, reverse transcriptase activity, Western blot, electron
      microscopy, and polymerase chain reaction showed them to belong to HIV-1 type.
      Reproduction of the isolates in cell cultures was accompanied by cytopathic
      effect and syncytium formation. The isolated strains can be divided into two
      groups: (1) the poorly growing isolates with low or negative RT and ELISA results
      and (2) the isolates with high infectivity, broad spectrum of cell tropism, and
      high levels of RT and ELISA. These data show the correlation of biological
      properties of HIV-1 strains isolated in the USSR with those of HIV strains
      previously isolated in Europe, USA, and Africa.

PMID- 1384239
TI  - [Changes in the properties of the influenza virus during persistence in the body
      of young mice with a slow influenza infection].

PMID- 1384240
TI  - [Deoxyoligonucleotide probes that differentiate antigenic and pathogenetic
      variants of the tick-borne encephalitis virus].
AB  - Experiments on molecular hybridization were carried out using a panel of 11
      deoxyoligonucleotide probes complementary to different parts of tick-borne
      encephalitis (TBE) virus, strain Sophyin, genome. Under study were the TBE virus
      strains differing by 3 criteria: (1) source of isolation (patients with acute and
      chronic TBE, Ixodes persulcatus and D. nuttalli ticks, small mammals); (2)
      serotype (eastern and Siberian Aina/1448), (3) virulence for Syrian hamsters. RNA
      of all the strains was hybridized with kDNA, 90% of strains with probe Sh5
      complementary to protein E gene, nucleotide positions 1285-1311. The highest
      differentiating capacity was observed with probes P131 and Sh3 complementary to
      genes of proteins ns2b and M. These probes reacted with RNA of 100% of highly
      virulent strains of the eastern serotype and only with 20-30% of strains of the
      Aina/1448 serotype of lower virulence. A certain differentiating capacity was
      demonstrated by probes Sh2 and P10 complementary to genes of prm and C proteins:
      they hybridized with RNA of 80% of eastern serotype strains highly virulent for
      hamsters and with only 20% of Aina/1448 serotype strains of low virulence. The
      panel of probes used revealed no significant differences among strains in
      relation to their isolation source, with the exception of a strain isolated from
      D. nuttalli ticks which reacted only with kDNA and probe P2 complementary to nsI
      protein gene, but not with other probes. The TBE virus strains isolated from
      patients with chronic TBE were shown to represent a genetically heterogeneous
      group.

PMID- 1384242
TI  - [The combined therapy of herpesvirus infection (experimental and clinical data)].

PMID- 1384243
TI  - Surgical and non-surgical treatment of cancer of the oesophagus and the
      oesophagogastric junction: results of 200 consecutive cases.
AB  - 200 consecutive, unselected patients with cancer of the oesophagus or the
      oesophagogastric junction (89 squamous, 110 adenocarcinoma or undifferentiated, 1
      oat cell) between 1984 and 1987 were reviewed. Resection with postoperative
      adjuvant irradiation in the cases of squamous cell cancer, was carried out in 51
      patients and non-surgical treatment [57 combined dilation and Nd-YAG-laser, 64
      iridium 192 high-dose rate brachytherapy with or without 60 Gy external beam
      irradiation (EBR); 28 endoprostheses] was performed in the remaining 149
      patients. The overall 5 year-survival rate was 9.2% (resections: 17.9%, non
      resected: 5.2%). Resected nodal negative T1 or T2 patients had the best prognosis
      (45.8% 5-year survival). The median survival following dilation and laser was 3.4
      months for all T-stages. Endoprostheses yielded a median survival of 1.7 months.
      Intracavitary brachytherapy gave the best palliative result with 6.5 months
      median survival, whereby only T1 and T2 patients benefitted from additional EBR.
      Histological subtype, age, sex or tumour localization did not influence survival.
      Multivariate analysis showed that in M0 patients the choice of treatment had a
      significant impact on prognosis.

PMID- 1384241
TI  - [The immunogenic activity of the Lassa virus structural proteins].
AB  - The immunogenic properties of Lassa virus GP1, GP2, and NP polypeptides were
      studied in rabbits. Lassa virus NP polypeptide, in contrast to GP1 and GP2
      polypeptides, was shown to induce the highest titres of antibodies determined by
      IFA and ELISA tests. Moreover, the antibody relative avidity experiment showed
      that the anti-NP antibodies has ELISA index of 0.63 whereas anti-GP1 and anti-GP2
      antisera had those of 0.49 and 0.28, respectively.

PMID- 1384244
TI  - Is it still worthwhile to treat bone metastases from differentiated thyroid
      carcinoma with radioactive iodine?
AB  - From 1964 to 1989, bone metastases were found in 28 of 600 patients operated on
      for differentiated thyroid carcinoma. Bone metastasis was the presenting symptom
      in 15 (54%) patients, was detected from the initial symptom in 4 (14.5%)
      patients, and occurred subsequently in 9 (32%) patients, with an average lag time
      of 4.5 years after surgical treatment. Pathological pattern of the thyroid cancer
      was follicular in 26 (93%) patients and papillary in 2 (7%) patients. Bone
      metastatic involvement was multiple in 21 (75%) patients and associated with
      other synchronous or metachronous distant metastases in 13 (46%) patients,
      especially in the lung (10 patients) or the brain (3 patients). The primary
      treatment of thyroid carcinoma was total thyroidectomy in all 28 patients, with
      additional modified neck dissection in 8 patients. All 15 patients presenting
      with symptoms had bone metastases demonstrated by x-ray studies. Six of the bone
      metastases only took up radioactive iodine 6 weeks after total thyroidectomy, as
      did 2 of 4 bone metastases detected at initial observation and 4 of 9
      metachronous bone metastases. All 12 patients with functioning bone metastases
      were given radioactive iodine therapy; 4 of the metastases were surgically
      resected. Only 2 patients with bone metastases showed a complete response after
      an ablative dose of I-131; none of the metastases had been demonstrated by x-ray
      studies. Radioactive iodine therapy cures no more than 17% of patients with bone
      metastases taking up radioactive iodine and 7% of all patients with bone
      metastases. All patients cured of bone metastases were given radioactive iodine,
      either alone, or combined with other treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384246
TI  - Hydroxyl radical-mediated conversion of morphine to morphinone.
AB  - 1. The hydroxyl radical-mediated conversion of morphine to morphinone (MO) was
      examined as an alternative to the enzymic reaction. 2. Hydroxyl radicals were
      generated by autoxidation of ascorbate in the presence of iron and EDTA. This
      system oxidized morphine to MO which was identified by h.p.l.c. and t.l.c. The
      reaction was dependent on the concentration of added Fe2+ and required the
      addition of ascorbate when Fe3+ was used. 3. Catalase inhibited production of MO
      whereas superoxide dismutase (SOD) had no effect. Addition of a large amount of
      H2O2 to the system resulted in a significant decrease in production of MO. No MO
      production was initiated by H2O2 itself. The oxidation of morphine was inhibited
      by typical hydroxyl radical-scavenging agents. These results indicate that
      morphine undergoes oxidation to MO by hydroxyl radical.

PMID- 1384247
TI  - [Therapy of the recurrence of malignant lymphoma].

PMID- 1384245
TI  - Invasion by cultured human follicular thyroid cancer correlates with increased
      beta 1 integrins and production of proteases.
AB  - A recognized model of tumor invasion requires cells to adhere to epithelial
      basement membrane and extracellular matrix components triggering release of
      proteases thus allowing cancer cells to invade the substrate. This adhesion is
      mediated by beta 1 integrins, a family of receptors to substrates such as
      collagen, laminin, and fibronectin. In order to study tumor invasion in
      follicular thyroid cancer (FTC), we used cell lines derived from a single
      patient's FTC primary tumor (FTC-133), neck lymph node metastases (FTC-236), and
      lung metastases (FTC-238). In vitro invasion as determined by the ability of the
      tumor cells to penetrate Matrigel was assessed by scanning electron microscopy.
      FTC-133 did not invade, FTC-236 was moderately invasive, and FTC-238 was highly
      invasive. Immunoprecipation with a monoclonal antibody to beta 1 integrin
      subunits and SDS-PAGE showed increased synthesis and flow cytometry showed
      increased expression of this subunit in FTC-236 and FTC-238 compared to FTC-133.
      Proteolytic activity was assessed by gelatin zymography. FTC-238 cell extract and
      conditioned media exhibited a more complex array of proteases consistent with
      activated type I collagenase and stromelysin compared to the less invasive
      clones, however 72 and 92 kd gelatinases consistent with type IV collagenases
      were present in the conditioned media from all three lines. In conclusion, in
      vitro invasion parallels in vivo metastasis by the source cells in the FTC
      133/236/238 cell-lines. The ability to invade basement membrane preparation
      correlates with increased synthesis and expression of beta 1 integrins and
      activation of tumor proteases.

PMID- 1384248
TI  - [The effect of low and high molecular weight dextrans on selected serum lipid
      parameters. 2].
AB  - The effect of dextran infusions on plasma levels of total cholesterol, LDL and
      HDL cholesterol, apolipoprotein B and AI and triglycerides is investigated within
      a patient group. Some plasma lipids and lipoproteins still remain significantly
      lowered after the end of the 10 days treatment period. Comparing the
      normolipidaemic with the hyperlipidaemic patients of type IIa and IIb the degree
      of alterations is different between these 3 groups.

PMID- 1384250
TI  - [Diagnosis and therapy of geriatric aphasia patients following cerebrovascular
      stroke].
AB  - Aphasia is common in elderly patients with stroke. This paper presents some
      results of aphasia therapy within the activation phase (acute aphasia) and the
      syndrome-specific learning phase (until the 24th week of treatment). A phase
      specific therapeutic concept was developed to connect stimulation and
      cirumvention method and compensatory techniques. The results attest to the
      success early after stroke regarding development of speech pathology logopedic
      diagnosis and therapy.

PMID- 1384249
TI  - [Endoscopic-sonographic control of cystogastric catheter drainage of
      pancreatogenic fluid collections].
AB  - In 1985, Hancke published a report on cystogastrostomy using a double pigtail
      catheter as an alternative to surgical drainage of pseudocysts. Between 1986 and
      1991, with the aim of testing the technique, we carried out a prospective study
      in 39 patients with 40 pancreatic collections of fluid. The object of the study
      was to identify those collections of fluid that would be suitable for
      cystogastric drainage. Among the first 20 patients thus treated, permanent
      evacuation of the cyst was achieved in eleven. In the other nine patients, the
      reasons for the failure of cystogastric drainage included to immature a cyst, too
      small a cyst, prior cyst infection and status after a BII resection. For the
      patients No. 21 to 40, these conditions were adopted as exclusion criteria, with
      the result that we were able to increase the percentage of permanent emptying to
      75%. This makes cystogastric drainage a genuine alternative to surgical and other
      drainage procedures. As a minimally invasive intervention, it is a first choice
      therapeutic procedure in suitable pancreatic pseudocysts. If cystogastric
      drainage is shown not to be feasible, the possibility of employing percutaneous
      drainage should be investigated. Surgical drainage procedures are reserved for
      use in such cases as cannot be treated with catheter drainage.

PMID- 1384251
TI  - [The limits of saving the extremity--amputation versus resection].
AB  - On the basis of the extensive data contained in the Vienna Bone Tumor Register,
      i.e. 839 primary malignant bone tumors, as well as of 554 cases treated at the
      Orthopedic Department of the University of Vienna Medical School, a comparison
      between the methods of surgery applied at pelvis and extremities during the past
      two decades can be drawn. Resectional therapy had been performed in twice as much
      patients as amputation therapy, and barely 20%, mostly with multiple metastases,
      had been merely treated with palliative surgery or were just biopsied and
      underwent chemo- and radiotherapy. An analysis of amputations and resections,
      subdivided into pelvis and sacrum resections, resectional reconstructions and
      resectional reimplantations at the extremities, shows approximately the same low
      incidence of local recurrences in the groups amputation versus resection, but a
      significantly higher involvement of pelvis and sacrum resections as well as no
      local recurrences in the group of 48 resectional reimplantations. As regards the
      oncologic radicality of surgical margins, in cases of resections, as compared to
      amputations, about twice as much inadequate operations had to be accepted,
      though. The fact that the local recurrences did not increase to the same degree,
      but were approximately equilibrated, seems to be due to the new chemotherapeutic
      treatment which had been initiated at the same time as the frequent application
      of resectional therapy. The conservation of extremities contains twice as high a
      risk of inadequate operation, but it is, in cases of effective chemotherapy,
      comparable with the former results of amputations, as regards local
      recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384252
TI  - [Development of new enzyme inhibitors for the treatment of AIDS[ ].
AB  - Two different approaches can be used to discover new lead structures for further
      drug design. Till now, de novo drug design, however, has not led to compounds
      active against HIV. The more classical approach, based on screening programmes,
      has led to the discovery of three different enzyme inhibitors active against HIV:
      transition state analogues (protease inhibitors), antimetabolites (azidothymidine
      and analogues as reverse transcriptase inhibitors), and TIBO and its congeners
      (reversible reverse transcriptase inhibitors).

PMID- 1384253
TI  - Postoperative hearing recovery in a case of delayed hearing loss after acoustic
      neurinoma removal.
AB  - Delayed postoperative hearing loss after acoustic neurinoma removal is seldom
      observed. The presented case illustrates the phenomenon of delayed postoperative
      hearing loss which was observed 4 days after removal of a large acoustic
      neurinoma. Intraoperative brainstem auditory evoked potentials (BAEP) revealed a
      gradual loss of wave V with preservation of wave I. In animal experiments a
      dissociated loss of BAEP has been associated with impairment of microcirculation
      due to secondary edema. Vasoactive treatment was initiated and after 11 days a
      partial hearing recovery could be documented. Transient disturbance in
      microcirculation of vasa nervorum of the cochlear nerve is assumed to be
      responsible for postoperative hearing fluctuation.

PMID- 1384254
TI  - [A comparative study of the diagnostic value of polyclonal and monoclonal
      antibodies to human IgM in immunoenzyme diagnostic agents].
AB  - Monoclonal antibodies (McAb) to human IgM, capable of recognizing antigenic
      determinants of different character, have been obtained. Three type-specific McAb
      have been used in diagnostic systems for the determination of specific IgM
      antibodies in the sera of patients with hepatitides A and B. The affinity
      constant and high specificity of McAb have made it possible to change affinity
      purified polyclonal antibodies to heavy chains of IgM for the gamma fraction of
      hybridoma-induced ascitic fluids without decreasing the sensitivity and
      specificity of test systems. The main advantages of McAb are the standard
      character of the reagent and reproducibility of its properties.

PMID- 1384255
TI  - [Role of liver transplantation in the treatment of metastatic disease of the
      liver].
AB  - The authors report their experience of liver transplantation for metastatic tumor
      in 6 patients. Although good palliation can be offered with prolonged survival in
      some patients, secondaries of the liver remain the poorest indication for liver
      transplantation. A prospective multicentric study would be needed to evaluate the
      usefulness of post-transplantation chemotherapy.

PMID- 1384257
TI  - Cell kinetics in skin disorders with disturbed keratinization.
AB  - A relatively simple immunohistochemical method was developed and used on cryostat
      sections. The monoclonal antibody Ki67 was used as marker for actively cycling
      cells and Pab601 for germinative cells. Counts were expressed as Ki67- or Pab601
      positive cells/mm. In order to improve our understanding of the pathogenetic
      mechanisms in skin disorders with disturbed keratinization we have measured cell
      kinetic values in dyskeratosis follicularis, pemphigus benigna familiaris
      chronica, autosomal dominant ichthyosis vulgaris, X-linked recessive ichthyosis,
      atopic dermatitis and psoriasis and compared them with previous values derived
      with autoradiography using tritiated thymidine. The results showed that
      microscopical acanthosis is related to an increase of the germinative population,
      while the increased epidermal turnover is associated with increased numbers of
      cycling cells. The cell kinetic changes seem to be all secondary except in
      psoriasis where a dysregulation in the epidermal growth may cause the epidermal
      changes. This simple method allows quick evaluation of drug efficacy which might
      be useful in atopic dermatitis and psoriasis.

PMID- 1384256
TI  - A prospective randomized study of two alternating, non cross-resistant
      chemotherapies for advanced Hodgkin's disease.
AB  - Fifty-four newly diagnosed patients with advanced Hodgkin's disease were
      randomized between two alternating non cross-resistant chemotherapies: MOPP-ABVD
      (MOPP: Mustine, Vincristine, Procarbazine, Prednisone-ABVD: Adriamycin,
      Bleomycin, Vinblastine, Dacarbazine) and MOPP-ABVD-CEM (CEM: Carmustine,
      Etoposide, methyl-GAG). There were no significant differences between the two
      therapies as far as complete remission, survival, relapse free survival and
      toxicity were concerned. This study does not support the use of MOPP-ABVD-CEM for
      improving the long-term outcome of patients with advanced Hodgkin's disease.

PMID- 1384258
TI  - Acute bilateral parotitis during chemotherapy for acute lymphoblastic leukemia.

PMID- 1384259
TI  - Aluminium hydroxide uptake in the stomach and in the intestine of the rat: a
      histochemical study.
AB  - Using the histochemical stains aluminon, solochrome azurine and solochrome
      cyanine, intracellular binding of aluminium was examined in the mucosa of the
      stomach, duodenum, jejunum and ileum of adult rats. A first group of rats (n =
      42) was sacrificed 1, 3, 6, 12, 24, 48 and 96 h after a single (300 mg x kg-1)
      oral administration of aluminium hydroxide. A second group of animals (n = 30)
      received daily the same dose of Al(OH)3 and was euthanatized after 3, 4, 5, 6 and
      7 days of treatment. Aluminium deposits occurred only in the antral glands of the
      stomach and in rats treated for at least 3 days. The reactive deposits are
      located in the cytoplasm of the upper glandular cells and in the lumen of the
      antral glands. These results suggest that aluminium is absorbed through the
      antral mucosa and may be re-excreted through the glandular mucus flow into the
      digestive lumen where it will be absorbed again. We hypothesize that the metal
      could act as a delayed-effect drug.

PMID- 1384261
TI  - CSF galanin and neuropeptide Y immunoreactivity in progressive supranuclear
      palsy.
AB  - Progressive supranuclear palsy (PSP) has been associated with degenerative
      changes in cholinergic and dopaminergic neurons in several brain regions. Since
      acetylcholine is colocalized with the neuropeptide galanin in certain neuronal
      populations, we measured the concentration of this neuropeptide and neuropeptide
      Y in cerebrospinal fluid (CSF) of 11 patients with PSP and in 16 age-matched
      healthy controls. No significant alterations in the CSF levels of galanin or
      neuropeptide Y were found.

PMID- 1384260
TI  - CSF neurotransmitter metabolites and short-term outcome of patients in coma after
      head injury.
AB  - The main metabolites of the neurotransmitters noradrenaline, dopamine, and
      serotonin, methoxy-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5
      hydroxyindoleacetic acid (5HIAA) respectively, were estimated by HPLC with
      electrochemical detection in CSF samples from 24 patients in coma after head
      injury, 1 to 12 (mean 3.0) days from accident, and from 24 age- and sex-matched
      subjects undergoing myelography for possible herniated disk. Analysis of variance
      with age as covariate, revealed significantly elevated levels of all three
      metabolites in the patients group. The concentrations of 5HIAA were negatively
      correlated to the score in the Glasgow Coma Scale. Fourteen patients who
      recovered with no or minor neurological deficits, had significantly lower CSF
      5HIAA levels compared to the ten patients who had a bad outcome (death), while
      there were no differences regarding HVA or MHPG concentrations. The possibility
      of a connection of the high neurotransmitter turnover during coma to the
      development of post-traumatic depression is discussed.

PMID- 1384262
TI  - IgM M-protein in a patient with sensory-dominant neuropathy binds preferentially
      to polysialogangliosides.
AB  - A 77-year-old man presented sensory-dominant neuropathy associated with IgM M
      protein reacting with various gangliosides. The M-protein bound to gangliosides
      with polysialosyl residue, such as GD1b, GD3, GT1b, GT3, GQ1b, and GQ1c. In
      addition, GD1a, GM3 and LM1, having a terminal monosialosyl epitope, were also
      recognized. Previously, Ilyas et al. described a similar case in which sensory
      symptoms were associated with IgM M-protein reacting with gangliosides containing
      a disialosyl group, such as GD3, GD1b, and GT1b, but not GM3 and GD1a. It is
      suggested that the reactivity of IgM M-protein with polysialogangliosides may be
      associated with the pathogenesis of sensory-dominant neuropathy.

PMID- 1384263
TI  - CSF myelin basic protein, IgG and IgM levels in 101 MS patients before and after
      treatment with high-dose intravenous methylprednisolone.
AB  - A total of 101 patients (62 women; 39 men) with definite MS were treated with
      1000 mg methylprednisolone (MP) intravenously for 10 consecutive days.
      Immediately before and after MP treatment clinical scoring (Kurtzke's Expanded
      Disability Status Scale) and CSF analysis were performed. Before MP treatment CSF
      MBP, IgG and IgM immunoglobulin levels (CSF Ig, index and intrathecal synthesis)
      were significantly elevated. The mean CSF MBP levels were significantly higher in
      the relapsing-remitting (RR) and chronic progressive MS patients with relapses
      (CP + RR) than in the CP group without a RR disease course, respectively 2.1, 2.3
      and 1.5 micrograms/l. A weak positive correlation was found between CSF MBP level
      and EDSS in the RR MS group (r = 0.34). CSF MBP was significantly correlated with
      IgM index (r = 0.36), IgM synthesis (r = 0.26), but not with the IgG levels.
      Therefore demyelination seems to be related to intrathecal IgM production. After
      MP treatment mean (median) EDSS decreased from 4.4 (4.0) to 3.3 (3.0). Except for
      Q albumin and IgM index, all CSF immunoglobulin levels decreased significantly
      after MP. The mean CSF MBP returned to reference values. In the RR group the
      decrease in CSF MBP was significantly correlated with the change in EDSS (r =
      0.39). CSF MBP seems to be a good parameter for disease activity in relapsing MS.
      Following treatment CSF MBP was found to be related with the change in IgM index
      (r = 0.30). MP treatment reduces CSF MBP and intrathecal IgM in a similar way
      indicating a relation between these 2 parameters.

PMID- 1384264
TI  - Neuronal uridine metabolism.
AB  - Uridine and other nucleic acids form part of RNA, DNA, coenzymes, second
      messengers, etc. Uridine uptake in nerve cells is an expression of neuronal RNA
      synthesis. More knowledge of uridine functions in neurones may give a better
      understanding of mechanisms underlying dementia, and they could be useful in
      treating brain tumors. Pakkenberg and co-workers have studied the uridine uptake
      in the brains of mice and monkeys under various conditions (after hypoxia, after
      carbon-dioxide treatment, after MPTP treatment, after electrostimulation, etc.)
      and the results are correlated with other biological brain parameters.

PMID- 1384265
TI  - Putative mechanisms of action of tacrine in Alzheimer's disease.

PMID- 1384266
TI  - Monoclonal antibodies with selective specificity for Alzheimer Tau are directed
      against phosphatase-sensitive epitopes.
AB  - A modified form of the microtubule-associated protein Tau is the major component
      of the paired helical filaments (PHF) found in Alzheimer's disease. The
      characterization of these posttranslational Tau modifications is hindered by the
      lack of sufficient PHF-Tau-specific markers. Here we describe several monoclonal
      antibodies, prepared by immunization with PHF, two of which showed a selective
      specificity for PHF-Tau without cross-reactivity with normal Tau. Epitope
      recognition by these two monoclonals was sensitive to alkaline phosphatase
      treatment. In Western blotting these monoclonal antibodies reacted specifically
      with the abnormally phosphorylated epitopes on Alzheimer's disease-associated PHF
      Tau. One of the new antibodies can be used for the construction of a sandwich
      enzyme-linked immunosorbent assay for the specific detection of PHF-Tau without
      cross-reactivity to normal Tau proteins.

PMID- 1384267
TI  - The fate of desmin and titin during the degeneration and regeneration of the
      soleus muscle of the rat.
AB  - We studied the fate of desmin and titin in rat skeletal muscle during a cycle of
      degeneration and regeneration induced in vivo by the inoculation of a snake
      venom. Cryosections of muscle were labelled using antibodies to the two proteins,
      and examined at fixed time points after venom injection. Early pathological
      changes in the muscle, such as hypercontraction, preceded the loss of desmin.
      Immunolabelling using anti-desmin antibodies showed that desmin bridges were
      still intact when adjacent myofibrils were no longer aligned. The results
      suggested that although the hydrolysis of desmin is not necessary for the
      hypercontraction of muscle fibres, it probably contributes to complete fibre
      breakdown. Titin, or at least the part which lies close to the M-line, remained
      intact longer than desmin, but was also hydrolysed prior to complete
      disintegration of the fibres. Both desmin and titin were re-expressed in the
      regenerating myotubes by 2 days after venom inoculation, and became well
      organised even before the myofibrils became aligned. We conclude that desmin and
      titin are involved in both establishing and maintaining the structural integrity
      of the muscle fibres.

PMID- 1384268
TI  - Determination of the early age of onset of equine recurrent laryngeal neuropathy.
      1. Muscle pathology.
AB  - The age of onset of equine recurrent laryngeal neuropathy has not been
      ascertained, although the clinical condition of left laryngeal hemiplegia
      ("roaring") has been recognized for centuries. The purpose of this study was to
      evaluate the laryngeal muscles of draft horse foals for the presence of fiber
      type grouping, indicating denervation and reinnervation, and to determine if
      histological evidence of recurrent laryngeal neuropathy was present. Abductor and
      adductor laryngeal muscles from the left and right sides were collected
      immediately after euthanasia from male draft horse foals, six less than 2 weeks
      and four 6 months of age, and stained for myosin ATPase. A morphometric test was
      used to objectively evaluate several areas from each muscle for fiber-type
      grouping. Extensive fiber-type grouping which was characteristic of recurrent
      laryngeal neuropathy was found in one of the young foals and all of the older
      foals. Four of the young foals had some areas of fiber-type grouping suggestive
      of mild, early changes associated with recurrent laryngeal neuropathy. One of the
      young foals had no fiber-type grouping present in any of the laryngeal muscles
      evaluated. These findings suggest an early age of onset of recurrent laryngeal
      neuropathy.

PMID- 1384269
TI  - Alexander's disease in infancy and childhood: a report of two cases.
AB  - Two cases of Alexander's disease are described. One case of infantile onset died
      at the age of 6 months and the second case was of the juvenile type with onset at
      2 years and death at 10 years. A clinical diagnosis of this disease is difficult
      since signs can vary according to the age of the patient. The severity of the
      pathological changes can also depend upon the age of onset of this disease, but
      they are restricted to the central nervous system. The Rosenthal fibre is the
      characteristic feature of Alexander's disease and we have examined for the first
      time its ultrastructure and immunocytochemical characteristics at the electron
      microscopical level and demonstrated coexpression of anti-glial fibrillary acidic
      protein and anti-ubiquitin antisera.

PMID- 1384270
TI  - Secretory meningioma associated with numerous meningothelial rosettes.
AB  - A case of secretory meningioma with numerous meningothelial rosettes is reported.
      A 66-year-old man with moyamoya disease gradually developed skull deformity, and
      underwent surgery for the skull tumor overlying the hemisphere. Histological
      examination disclosed numerous meningothelial rosettes quite similar to those
      induced by subarachnoid injection of epinephrine and pseudopsammoma bodies
      described by Kepes. This may be the first case of meningioma associated with
      numerous rosette formations.

PMID- 1384271
TI  - Pseudomembranous and membranous conjunctivitis. Immunohistochemical features.
AB  - A 63-year-old man, who had for one month been on sulfasalazine therapy, developed
      general malaise, high fever, severe stomatitis, and bilateral necrotizing
      pseudomembranous conjunctivitis with corneal erosion, identical to that seen in
      the Stevens-Johnson syndrome. Topical therapy with antibiotics and aprotinin
      rapidly healed the corneal surfaces, while densely adherent true membranes
      developed on the conjunctiva, and were removed surgically several times during
      the next week. After the acute stage, subtle subepithelial conjunctival scarring,
      superficial punctate keratitis, dry eye syndrome and fluctuating irregular
      corneal astigmatism became evident, but good visual acuity, lid function and
      ocular motility were retained. Histopathologic study of conjunctival membranes
      from two cases of membranous conjunctivitis revealed polymorphonuclear leukocytes
      within a matrix composed of fibrin, tenascin and fibronectin. In older membranes,
      histiocytes were additionally found. Surgical debridement of such membranes
      removes a substratum of inflammatory debris that is likely to promote secondary
      infection, fibrosis and symblepharon formation, and may decrease rather than
      increase subsequent scarring of the necrotized conjunctiva.

PMID- 1384272
TI  - An immunohistochemical and ultrastructural study of case of small-cell
      neuroendocrine carcinoma in the ampullary region of the duodenum.
AB  - One case of small-cell neuroendocrine carcinoma in the ampullary region of the
      duodenum is reported. The histological appearance of the tumor was identical to
      pulmonary small-cell carcinoma. Neuroendocrine differentiation was demonstrated
      immunohistochemically by positive immunoreaction for neuron specific enolase, Leu
      7 and chromogranin, and ultrastructurally by the presence of scanty dense-core
      neurosecretory type granules. Small-cell neuroendocrine carcinoma in the ampulla
      of Vater is extremely rare. To our knowledge, this is the sixth reported case.

PMID- 1384273
TI  - Ontogeny of glycerol phosphate dehydrogenase-positive oligodendrocytes in rat
      brain. Impaired differentiation of oligodendrocytes in the myelin deficient
      mutant rat.
AB  - The ontogeny of oligodendrocytes in the myelin deficient (md) rat mutant and in
      control rats was explored immunohistochemically using an antiserum against the
      oligodendrocyte specific enzyme, glycerol phosphate dehydrogenase (GPDH), and the
      avidin-biotin complex technique. In control rats, GPDH was demonstrated to be
      expressed relatively early in oligodendrocyte differentiation, prior to either
      myelin basic protein or proteolipid protein expression. With development,
      oligodendrocytes containing GPDH increased in number, apparent staining
      intensity, cell soma area and process elaboration. Fewer GPDH+oligodendrocytes
      were observed in the brain of mutant rats than in unaffected littermates at all
      developmental ages, and major developmental increases in oligodendrocyte density
      were delayed. The density of GPDH+oligodendrocytes was reduced by about 40% in
      both the corpus callosum and in the cingulate cortex of P22-25 and mutants
      compared with control rats. The oligodendrocyte cell soma area was not influenced
      by the md condition, and increased 2-fold with development in rats of both
      genotypes. The area of coronal sections occupied by the corpus callosum increased
      about 2.5-fold with development, and was 30% smaller in mutant rats late in their
      lifespan than in unaffected littermates. The reductions in oligodendrocyte
      density reported here are of insufficient magnitude to fully account for
      biochemically measured reductions in oligodendrocyte gene expression accompanying
      the md trait, indicating that gene expression per oligodendrocyte is also
      impaired. Cell counts in control rats also revealed that oligodendrocytes are
      overproduced during development. Cell density and the total number of corpus
      callosum GPDH+oligodendrocytes per section were maximal at P22-25 and then
      decreased to adult values. These results suggest that glial cells, like neurons,
      may be generated in excessive numbers, and some subsequently die, as a normal
      concomitant of development.

PMID- 1384274
TI  - Effect of seizure activity and calpain inhibitor I on LTP in juvenile hippocampal
      slices.
AB  - Kainic acid-induced seizure activity in adult rats produces an impairment of long
      term potentiation induction in hippocampal slices. As the consequences of seizure
      activity are different in adult and juvenile rats, we tested the ability of
      hippocampal slices prepared from kainate-treated juvenile rats to exhibit long
      term potentiation. Long-term potentiation was induced by theta-burst stimulation
      and was not significantly different in slices prepared from control or kainate
      injected juvenile rats (16-18 postnatal days). Short-term potentiation, however,
      was reduced in the kainate-treated juveniles. Calpain inhibitor I has been shown
      to prevent long-term potentiation formation in adult hippocampal slices, and we
      evaluated its effect on long-term potentiation in hippocampal slices from
      juvenile rats. Calpain inhibitor I produced a significant reduction in the degree
      of long-term potentiation induced by theta-burst stimulation in hippocampal
      slices prepared from 14-20 postnatal day-old animals. The results are consistent
      with the notion that, although similar mechanisms participate in the formation of
      long-term potentiation in juvenile and adult animals, juvenile animals are much
      more resistant than adult animals to the consequences of seizure activity.

PMID- 1384275
TI  - Behaviour of several 'progression markers' during the HIV-Ab seroconversion
      period. Comparison with later stages.
AB  - Two acute phase reactants, four cytokines, five soluble factors and lymphocyte
      subpopulations have been simultaneously evaluated in 16 subjects before and
      closely after the HIV-Ab seroconversion time. The same variables have also been
      determined in 50 HIV-Ab-negative high risk subjects, in 36 CDC II-III and in 30
      CDC IV patients, utilizing a mixed longitudinal epidemiological model. The
      results show significant variations of few parameters in the early phases
      (increase: sCD8, beta-2-Microglobulin, sIL-2R, sCD23, Neopterin, IFN-alpha;
      decrease: CD4+ lymphocytes). In the course of the disease, many others parameters
      progressively increase (IFN-tau, IL-4, IL-6, acid-alpha 1-glycoprotein, alpha 1
      antitrypsin) or decrease (B- and T-lymphocytes). Ferritin, in particular, highly
      increases only in CDC IV stage. These data may be useful to monitor patients
      during the entire course of their disease and to suggest the time elapsed from
      seroconversion.

PMID- 1384277
TI  - Speech--a key function of man. Reflexions of a neurosurgeon.
AB  - Man is distinguished and differentiated from other living creatures by possessing
      less genetically determined characteristics, behaviour and reactions, with fewer
      features fitting him for a special environment. For this reason he enjoys greater
      freedom and adaptability. In order to be able to pass on the necessary lessons
      for survival, man must have command of his speech, and as a species can only
      exist within communities. This presupposes an instinctive drive to make rules and
      regulations for ordered living in society. Speech is not only a means of
      communication but also the basis and precondition of abstract thinking. Complete
      aphasia implies the loss of this ability. It would deprive man from the most
      important of his key functions. Therefore it is inhuman. These reflections have
      convinced me absolutely, that neurosurgical interventions, which would have the
      predictable result of total aphasia, must not be performed, even though
      prolongation of life, but without speech, might thus be bought.

PMID- 1384276
TI  - Neuroendocrine regulation of cyclic AMP formation in osteoblastic cell lines (UMR
      106-01, ROS 17/2.8, MC3T3-E1, and Saos-2) and primary bone cells.
AB  - The effect of four different neuropeptides and norepinephrine (NE) on cyclic AMP
      formation in four different osteoblastic cell lines and in isolated neonatal
      mouse calvarial bone cells has been examined. In the rat osteosarcoma cell line
      UMR-106-01, vasoactive intestinal polypeptide (VIP, 0.001-1 microM), calcitonin
      gene-related peptide (CGRP, 0.3-30 nM), and NE (0.1-300 microM), but not
      neuropeptide Y (NPY, 0.001-1 microM) or substance P (SP, 0.1-10 microM), caused a
      dose-dependent stimulation of cyclic AMP formation. The stimulatory effects were
      synergistically potentiated by forskolin (0.1-3 microM). The effects of NE and
      VIP were time dependent, with an optimal effect seen at 5 minutes. The amount of
      cyclic AMP accumulated in cells stimulated with NE and VIP was in the same range.
      The amplitude of the cyclic AMP response induced by CGRP was smaller than that
      caused by VIP and NE. In the human osteosarcoma cell line Saos-2, NE (0.1 microM)
      and VIP (0.3 microM) stimulated cyclic AMP formation, and the effect was
      synergistically potentiated by forskolin. In the absence of forskolin, no effect
      of CGRP (30 nM) could be seen in the Saos-2 cells, but in the presence of
      forskolin (3 microM) a stimulatory effect was observed. SP and NPY did not change
      basal cyclic AMP levels in Saos-2 cells. In the osteoblastic osteosarcoma cell
      line of rat, ROS 17/2.8, NE (0.1 microM) caused a significant stimulatory action
      on cyclic AMP formation that was synergistically potentiated by forskolin (3
      microM), VIP, CGRP, and SP did not affect the cellular content of cyclic AMP in
      ROS 17/2.8.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384278
TI  - Antigen specific suppressor T cells respond to cytokines released by T cells.
AB  - These studies were conducted to examine the cytokine requirement for clonal
      expansion of regulatory T cells. It was observed that the in vivo administration
      of recombinant IL2 (rIL2), rIL5 or interferon (IFN) gamma at the time of
      immunization with pneumococcal polysaccharide Type III (SSS-III) resulted in
      substantial suppression of the antibody response in each case. Using our well
      established cell transfer system we found that such suppression of the antibody
      response could be transferred using 10-100-fold fewer primed spleen cells
      providing these cells were treated in vitro with rIL2 before cell transfer;
      spleen cells from unimmunized mice or from mice primed with an unrelated antigen
      and then treated with rIL2 did not cause suppression of the antibody response to
      SSS-III, thereby eliminating the possibility of non-specific carry-over effects
      induced by rIL2. We also found that the in vivo administration of anti-IL2
      receptor antibody inhibited the generation of Ts cells in vivo. Spleen cells from
      SSS-III primed animals treated with rIL4, rIL5 and IFN gamma--but not rIL6-
      likewise are able to transfer suppression of the antibody response with fewer
      cells than that required using primed cells not treated with cytokines. Thus,
      these studies indicate that Ts cell activity is greatly influenced by cytokines.
      The studies also suggest that these cytokines may be required during the
      activation and/or clonal expansion of Ts cells.

PMID- 1384279
TI  - Identification and characterization of mammalian cell membrane receptors for LPS
      endotoxin.

PMID- 1384280
TI  - Immunomodulators and fungal infections: use of antifungal drugs in combination
      with G-CSF.

PMID- 1384281
TI  - Biologic response modifiers as antivirals in immunosuppressed hosts.
AB  - A wide variety of immunomodulators/biologic response modifiers (BRM) have been
      demonstrated to provide broad spectrum antiviral activity against both RNA and
      DNA viruses in several animal species. Dramatic decreases in mortality, reduced
      virus titers in tissues, and reduced histopathology can be produced. The
      antivirally effective agents include microbially derived materials, polyanions,
      cytokines, and chemically diverse small molecular weight chemicals. Antiviral
      efficacy with BRM treatment has been shown in numerous kinds of
      immunosuppression, emphasizing the potential for BRM treatment in
      immunocompromised patients. The greatest protective effects are observed with
      prophylactic or early therapeutic treatment. BRMs act indirectly, most likely by
      activating cells and/or inducing antiviral mediators early in the course of viral
      pathogenesis. In general, viral specific immune responses in BRM-treated and
      infected mice are absent or similar to those in untreated mice. Because BRMs are
      pleiotropic in their immunomodulatory effects, it has been difficult to establish
      whether one cell type or mediator is critical for the broad spectrum antiviral
      activity. Interferon appears to be critical for some small molecular weight
      synthetic compounds, but does not appear to explain all the antiviral activity of
      certain large molecular weight polyanions. Whether there is a unified antiviral
      mechanism among different BRMs remains to be determined.

PMID- 1384282
TI  - [The gamma nail. A new implant for the management of hip para-articular
      fractures].
AB  - An alternative treatment of fractures of the coxal femur side is a new implant
      called "GAMMA-NAIL". The article describes the new implant and the operative
      technique. Furthermore, we present the results of a first series of 58 patients,
      mainly women (w:m = 8:1) with an average on age of 78.09 years. Although these
      patients were characterised by a number of complicating factors, it was possible
      to mobilise 86.2% at an average of 9.4 days after surgery with full load. We
      present a report on the quality of walking, a pain report, data on the mobility
      of joints and the x-ray findings. The 5.1% of infections and 8.6% of operative
      and postoperative complications we have to face, are described in detail.

PMID- 1384283
TI  - Epidemiology and comorbidity. The North Dakota prevalence studies of Tourette
      syndrome and other developmental disorders.

PMID- 1384284
TI  - Characterisation of passively transferred antigen arthritis induced by methylated
      bovine serum albumin in the rat: effect of FK 506 on arthritis development.
AB  - The conditions necessary for the passive transfer of antigen arthritis induced by
      methylated bovine serum albumin (mBSA) in the rat have been studied. Spleen cells
      from immunised rats were not capable of transferring disease unless they were
      first activated in culture with mBSA or concanavalin A. Cells from sham-immunised
      animals could not be activated to transfer the arthritis. The immunosuppressant
      drug FK 506 could inhibit the development of the arthritis when present during
      the activation period in culture or when dosed to the recipients of activated
      cells.

PMID- 1384285
TI  - Simultaneous fluorometric determination of intracellular polyamines separated by
      reversed-phase high-performance liquid chromatography.
AB  - A reversed-phase HPLC technique in combination with fluorescent detection is
      described for simultaneous quantification of the precolumn Dansyl derivatives of
      intracellular amines. The derivatives were stable for at least one week, kept
      protected from the light at -20 degrees C. The detection limit was between 1 and
      5 pmol for all tested polyamines. Serotonin coeluted with tryptamine. The method
      has a very good reproducibility for both, retention times and chromatographic
      peak areas. The average recovery of standard amine solutions added to cellular
      extracts was estimated to be higher than 90%. The described method enables a
      rapid, reliable and reproducible quantification of biogenic and related
      polyamines in biological fluids and tissues.

PMID- 1384286
TI  - Modulation of neurally mediated airway microvascular leakage in guinea-pig
      airways by beta 2-adrenoceptor agonists.
AB  - The effect of two beta 2-adrenoceptor agonists, salbutamol (100 micrograms/kg
      i.v.) and broxaterol (100 micrograms/kg i.v.), on airway microvascular leakage
      induced by vagal stimulation was studied in anaesthetised guinea pigs. Airway
      microvascular leakage was measured by Evans blue extravasation. Broxaterol, but
      not salbutamol, inhibited Evans blue dye extravasation at all airway levels, an
      effect prevented by pretreatment with propranolol (1 mg/kg). Neither of the beta
      2-agonists had any effect on substance P-induced Evans blue dye extravasation.
      Broxaterol inhibits the prejunctional release of tachykinins from airway sensory
      nerves by stimulation of beta-receptors. The mechanism by which beta-adrenoceptor
      agonists prevent airway microvascular leakage deserves further study.

PMID- 1384287
TI  - Dexamethasone induces a down regulation of rat mast cell protease II content in
      rat basophilic leukaemia cells.
AB  - Corticosteroids are widely used to treat severe allergic and inflammatory disease
      in which mast cells have been implicated as playing an important role. It has
      been previously shown that in vivo treatment with large bolus doses of
      corticosteroid can induce a down regulation of the number of IMMC in the rat.
      Previous in vitro studies of the RBL cell line have shown that culture in the
      presence of high doses of dexamethasone can induce an increase in cellular
      histamine content similar to that induced by other agents known to reduce the
      rate of cell division such as 5-hydroxyurea or sodium butyrate. In our studies
      the rat mucosal mast cell like cell line RBL-2H3 was cultured in the continuous
      presence of dexamethasone for periods of up to 4 weeks. Cell-associated histamine
      levels were found not to increase significantly at the doses of the
      corticosteroid we used. Of greater interest was the observation that levels of
      the mucosal mast cell specific protease RMCPII were dramatically reduced in these
      dexamethasone-treated cultures even at doses that might be considered to be
      physiologically relevant. This effect could be observed at 3 days after
      dexamethasone treatment and a continued reduction of RMCPII content was noted up
      to 4 weeks, at which time RMCPII levels were less than 5% of the control values
      in 10(-7) M dexamethasone treated cells. 5-Hydroxyurea did not reduce cellular
      RMCPII content even at a concentration which substantially reduced the rate of
      cell division and significantly increased cell associated histamine
      content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384288
TI  - Changes in corticosterone levels under different degrees of acute inflammation in
      mice.
AB  - Carrageenan of different concentrations was injected into the 6-day-old air pouch
      in mice. It was found that 12 mg carrageenan caused a significant increase of
      plasma and exudate corticosterone levels at 24 h, while 1 and 3 mg carrageenan
      could only induce a significant increase of exudate corticosterone at 4 h.
      Elevation of corticosterone in both plasma and inflammatory exudate appeared to
      be correlated, suggesting that the exudate corticosterone was derived from the
      blood circulation. Injection of exogenous histamine and PGE2 into the air pouch
      induced a significant increase in exudate levels of corticosterone. However,
      plasma corticosterone increased significantly only after histamine
      administration, although a slight increase was observed in those injected with
      PGE2. These findings thus suggest that endogenous histamine and PGE2 which are
      released during carrageenan-induced acute inflammation, as shown in our previous
      work, might be responsible for the increase of corticosterone in both plasma and
      inflammatory exudate.

PMID- 1384289
TI  - [Effect of pan-retinal photocoagulation in iris neovascularization].
AB  - The authors were able to produce experimental rubeosis iridis in the rhesus
      monkey's eye on 5 days following occlusion of the major retinal vessels and
      persistent ocular hypotony. Histopathological examination revealed true
      neovascularization. This experiment attempted to see whether laser pan-retinal
      photocoagulation plays an inhibiting effect on the occurrence of rubeosis iridis
      or not. We first performed laser pan-retinal photocoagulation, and at the same
      time performed occlusion of the major retinal vessels and persistent hypotony to
      aid for rubeosis iridis. Clinically, rubeosis iridis appeared within 5 days. At
      14 days, histological examination revealed vessels on the surface of the iris
      following pan-retinal photocoagulation treatment were covered by fibroblast and
      melanocyte, and their endothelial cells showed no fenestrations. This means that
      clinical rubeosis iridis is not true neovascularization, but dilatation of the
      iris vessels. Thus, it was confirmed that pan-retinal photocoagulation inhibits
      development of iris neovascularization.

PMID- 1384291
TI  - [Correlation between volumetric endosonography and prostate weight. Variation
      according to histological type].
AB  - Correlation between endosonographic volumetry and prostatic weight, accuracy
      according to histopathology. We report a study over 50 patients who underwent
      TURP, demonstrating statistical correlation between endosonographic volumetry and
      prostatic weight. We observe a difference in accuracy according to histopathology
      and we discuss the reliability of the technique. We conclude that variability is
      due to the sensitivity of the examination.

PMID- 1384290
TI  - The contribution of transrectal ultrasonography in the early diagnosis of
      prostate cancer.
AB  - Two hundred twenty asymptomatic males, aged 55 to 75 years old, underwent
      transrectal ultrasonography of the prostate as part of a screening examination.
      Fifteen prostate adenocarcinomas were detected, 5 of which were nonpalpable. The
      biopsies were performed under sagittal ultrasound guidance. Serum prostatic
      specific antigen and prostatic acid phosphatase levels were also obtained from
      each patient. Nine of the patients were staged as B2, one patient as D2, 4
      patients as A1 and one as A2. The use of transrectal ultrasonography as a
      screening tool must be further evaluated in a multicenter trial with a large
      number of patients.

PMID- 1384292
TI  - [Prostatic cancer after transurethral resection for benign prostatic
      hypertrophy].
AB  - Five cases of prostatic cancer developed after transurethral resection of
      prostate for benign hypertrophy are reported. Duration of transurethral resection
      of prostate (TUR-P) to diagnosis of prostatic cancer ranged from one year and
      seven months to seven years and two months, on average four years and seven
      months and frequency of prostatic cancer after TUR-P was estimated at 1.2%. Four
      of five patients complained of macroscopic hematuria. The cystourethrogram showed
      the mass protruded in the dilated prostatic urethra or bladder-neck in four
      patients (80%), a remarkable finding, and four cases were at stage D. Risk of
      development of prostatic cancer is not decreased even after prostatectomy and
      prostatic carcinoma diagnosed after TUR-P often advances in stage. Therefore,
      periodical examinations of the patients who had a prior prostatectomy are very
      important.

PMID- 1384293
TI  - [A study on the mass screening system for prostatic diseases].
AB  - Between 1984 and 1990, a mass screening for prostatic diseases was carried out on
      men over 55 years old in cities, towns and villages in Toyama Prefecture, Japan.
      The total number of subjects examined in the primary study was 1,232, which was
      17.7% of the males over 55 years old in these areas. The primary study consisted
      of inquiry concerning urination, digital examination of the prostate,
      transabdominal ultrasonography, and determination of tumor markers. A secondary
      study was indicated for 100 subjects (8.9%) suspected to have prostatic cancer
      and 169 (15%) suspected to have benign prostatic hypertrophy, but only 92 (35%)
      of them were actually examined. Prostatic cancer was histologically diagnosed in
      3 subjects (0.3%), and benign prostatic hypertrophy was established in 56
      subjects (4.5%), who were referred to urologists. Though a high percentage of the
      population was covered by the primary study the percentage of subjects who
      received the secondary study among those in whom it was indicated was low. This
      probably was a reason for the low detection rate of prostatic cancer. An improved
      system is considered to be needed to increase the efficiency of mass screening
      for prostatic diseases.

PMID- 1384294
TI  - [A case of tranilast-induced cystitis with transient ECG changes].
AB  - A case of tranilast (Rizaben)-induced cystitis accompanied with possibly
      hypereosinophilic heart syndrome was described. A 75-year-old male, who had been
      taking tranilast for allergic dermatitis for two months, was admitted for severe
      bladder stimulating symptoms which was unresponsive to antibiotic therapies.
      Clinical examination revealed tenderness of the prostate, aseptic pyuria,
      eosinophilia, liver dysfunction and electrocardiographic disorders including
      atrial fibrillation, T-wave inversions and lowered ST segment without any cardiac
      symptoms. Cystitis symptoms, pyuria, eosinophilia and liver dysfunction improved
      within several days after discontinuance of tranilast, and ST-T changes on ECG
      gradually normalized within a few months. Tranilast-induced cystitis has been
      demonstrated as a type of eosinophilic cystitis. Since pathologic findings of
      eosinophilic cystitis and hypereosinophilic heart syndrome are markedly similar
      and all symptoms and signs disappeared after deprivation of tranilast, it appears
      likely that eosinophilic inflammation was induced to the heart, liver, bladder
      and prostate of the current patient by tranilast.

PMID- 1384295
TI  - [Antiandrogen therapy of benign prostatic hypertrophy: clinical effects of
      allylestrenol evaluated by transrectal ultrasonographic measurement].
AB  - A multicenter trial was carried out on 100 patients with benign prostatic
      hypertrophy to elucidate the efficacy of anti-androgen therapy with allylestrenol
      (AE). AE was administered at a daily dose of 50 mg for 16 weeks to the patients
      and its efficacy was evaluated with subjective symptom scores, residual urine
      volume and uroflow rates. The effects of AE on prostatic volume and morphology
      were evaluated using transrectal ultrasound. Of these patients 65 completed the
      protocol, and only three patients withdrew from the study owing to side effects.
      Very modest adverse effects on sexual performance were seen in one patient. In
      this study, significant beneficial effects of AE on symptom scores, residual
      urine, maximum flow rate, and prostate size were demonstrated. However,
      volumetric reduction was not associated with urodynamic improvement. Prostatic
      shape was not changed throughout the study. These findings suggest that
      allylestrenol can be used as an alternative to prostatectomy in patients who are
      at high risk for surgery.

PMID- 1384296
TI  - [Pure yolk sac tumor of the testis with brain metastasis: report of an adult
      case].
AB  - Herein we report an adult case of pure yolk sac tumor with brain metastasis. The
      patient was a 37-year-old male who presented with indulation of his left scrotum
      for 10 months. The plain computerized tomographic (CT) scan on entry demonstrated
      tumor metastasis to his lung and liver and serum alpha-fetoprotein (AFP) level
      was 786 ng/ml. Five days after admission, he developed hemiplegia secondary to
      the cerebral metastasis and hemorrhage. After chemotherapy and operation of right
      posterior lobectomy, PVB (cisplatinum, vinblastine, bleomycin) chemotherapy
      produced a complete remission and the elevated serum AFP was normalized. However,
      the second course of chemotherapy had to be discontinued because of drug-induced
      hepatitis. He died of massive tumor metastasis to his brain 6 months after
      craniotomy.

PMID- 1384297
TI  - [Clinical effects of distigmine bromide (Ubretid), a cholinesterase inhibitor, on
      micturition disturbance by benign prostatic hypertrophy--comparative study of
      distigmine bromide and the combination of distigmine bromide and adrenergic
      blocker].
AB  - We report the results of a comparative study on the clinical efficacy of the
      single use of distigmine bromide and its combined use with prazosin hydrochloride
      in the treatment of benign prostatic hypertrophy. The single use and combined use
      groups were administered 10 mg/day of distigmine bromide and the same with 1
      mg/day of prazosin hydrochloride for a period of 8 weeks respectively. In the
      single administration group, marked improvement was found in one patient (9%),
      moderate improvement in 4 patients (36.3%), slight improvement in 3 patients
      (27.2%) and aggravation in 3 patients. In the combined use group, marked
      improvement was found in one patient (11.0%), moderate improvement in 5 patients
      (55.5%), and slight improvement in 3 patients (33.3%). No significant differences
      were found in the improvement rate between the two groups. However, significant
      improvements were found in both groups for the subjective symptoms of urinary
      disturbance, diurnal and nocturnal frequency. As a result of the examination of
      objective findings, a significant decrease in residual urine ratio was also shown
      in both groups, while significant improvement for average flow and maximum flow
      rates were found in only the combined use group. In conclusion, distigmine
      bromide and distigmine bromide+prazosin hydrochloride are considered very useful
      for the treatment of miturition disturbance due to benign prostatic hypertrophy.

PMID- 1384298
TI  - Self-expanding metal stents for palliative treatment of malignant ureteral
      obstruction.
AB  - OBJECTIVE: We studied the immediate and long-term efficacy of the Wallstent
      device in the treatment of ureteral obstruction caused by malignant disease.
      SUBJECTS AND METHODS: In 23 patients (30 ureters), self-expanding metal stents
      were implanted endoscopically (n = 23), percutaneously (n = 5), or
      bidirectionally (n = 2) because of extrinsic malignant ureteral obstruction.
      Patients who met the following criteria were selected for stent implantation: (1)
      life expectancy of at least 6 months, (2) current polychemotherapy, (3)
      increasing levels of serum creatinine, and (4) severe clinical signs and symptoms
      associated with hydronephrosis. Obstruction was diagnosed by using sonography and
      excretory urography. After radiologic localization and dilatation of the
      stenosis, the Wallstent device was inserted. For 4 weeks, a double-J catheter
      inserted through the stent was kept in place in order to prevent obstruction by
      reversible hyperplastic reaction of the urothelium. Patients were followed up for
      31 weeks (range, 3-75 weeks). Follow-up included sonography, excretory urography,
      and determination of serum levels of creatinine in all cases and furosemide
      scintigraphy and the Whitaker test in selected cases. RESULTS: Implantation of
      the Wallstent device was successful in 30 (97%) of 31 cases attempted. The
      survival rate was 81% after 6 months and 61% after 8 months. The primary patency
      was 83% after 30 weeks. Complications were macrohematuria (one patient) and
      incrustation (two patients). No infection and no migration or compression of the
      stent were observed. CONCLUSION: Implantation of a Wallstent device is a safe and
      effective alternative to double-J catheter placement in tumor-associated ureteral
      obstruction.

PMID- 1384299
TI  - Comparison between cetirizine and terfenadine: time-response study.
AB  - Six young healthy volunteers were used as experimental models to study the
      efficacy of cetirizine 10 mg and terfenadine 60 mg with regard to the onset of
      action and duration of the peripheral antihistaminic effect (cutaneous activity).
      For this purpose, 10 micrograms of histamine were used administered as
      intradermal injection at the internal border of the forearm at times 0', 30',
      60', 90', 120', 180', 240', 360', 480' and 24 h after the intake of the drug,
      with a minimum interval of 7 days between one drug and the other. The inhibition
      of the cutaneous activity of histamine was assessed by planimetry of the papule
      transferred to adhesive paper. Both antihistamines were well tolerated by the
      oral route and our patients did not refer any anticholinergic side effects nor
      sedation, which are classically described in relation to first generation anti-H1
      drugs. When comparing both antihistamines as to their ability to inhibit the
      response, there are no differences between them at 30', but from this time point
      up to 24 h cetirizine inhibits significantly more than terfenadine the response
      to histamine; cetirizine achieves its maximal effect at 180', while terfenadine
      does so at 240'; both drugs maintain their maximal effect antil 480' and, as was
      previously mentioned, at these doses cetirizine shows a higher percentage of
      inhibition than does terfenadine at equal time points.

PMID- 1384300
TI  - [Occupational hypersensitivity to spiramycin. Report of a case].
AB  - A case report of occupational hypersensitivity to Spiramycin. Rhinoconjunctivitis
      and spasmodic cough are reported in a 34 year-old female handling spiramycin
      powder in a pharmaceutical factory. The symptoms appeared within the first few
      hours of coming into contact with the drug and continued for several hours after
      leaving her place of work. The patient had no personal case history of atopy.
      Results for prick-test with extracts using a concentration of 1/100 (w/v) were
      positive, as were results por intradermical tests with a solution using a
      concentration of 1/10.000 (w/v). The diagnostic was confirmed with the
      application of a nasal provocation test. Our criteria to determine positivity to
      this test was according to Bachman (1) and the European Committee of
      Rhinomanometry. On our suggestion the patient was transferred to another section
      of the pharmaceutical company whereupon all symptoms disappeared immediately and
      no further allergic reactions to drugs were registered. This case suggest that
      reactions to a chemical product may involve immunological mechanisms.

PMID- 1384301
TI  - Scabies.
AB  - Scabies is highly contagious and is usually transmitted by direct personal
      contact. It typically presents as an intensely pruritic eruption. Atypical
      presentations are common in Norwegian scabies and in childhood scabies.
      Infestation is documented by visualizing the mite, its eggs or scybala on low
      power microscopy. The treatment of choice is 5 percent permethrin cream, used in
      a single application at bedtime and removed the next morning.

PMID- 1384302
TI  - Arrhythmias after cardiac transplantation.
AB  - The etiology and clinical significance of sustained arrhythmias, and atrial and
      ventricular premature complexes (APCs and VPCs, respectively) after heart
      transplantation are controversial. Fifty adult recipients surviving > 2 weeks
      were studied by continuous telemetry while in the hospital and by ambulatory
      electrocardiographic monitoring at 2, 4, 6, 12 and 24 weeks after
      transplantation. The median APC frequency was greater among subjects who
      experienced allograft rejection in the early postoperative period (0.7/hour,
      range 0 to 23) than among those who did not (0.2/hour, range 0 to 10.4) (p =
      0.04). The APC frequency in all subjects decreased from 0.25/hour (range 0 to 23)
      early to 0/hour (0 to 14) later (p = 0.04). Atrial flutter was the most frequent
      sustained arrhythmia; it was recorded in 5 of 21 rejectors and in 1 of 29
      nonrejectors (p = 0.04), and 11 of 16 episodes (69%) were related to acute
      rejection temporally. VPCs were recorded in all patients early after
      transplantation, but the median frequency subsequently decreased from 4.6/hour
      (range 0.5 to 470) early to 1.25/hour (range 0 to 225) later (p < 0.001). VPC
      frequency was unrelated to rejection. Sustained ventricular tachycardia was
      recorded once and was caused by the proarrhythmic effect of flecainide. Thus,
      APCs and VPCs occur frequently after transplantation. Frequent APCs are
      associated with rejection, whereas the main determinant of VPC frequency is time
      after transplantation. Atrial flutter is closely associated with rejection and
      should be regarded as an indication for endomyocardial biopsy. Ventricular
      tachycardia occurs seldom, and in this study was due to proarrhythmic drug
      effects.

PMID- 1384303
TI  - Comparison of intravenous dosing regimens for maintaining steady-state
      procainamide levels during programmed ventricular stimulation.

PMID- 1384305
TI  - Eating behavior and adherence to dietary prescriptions in obese adult subjects
      treated with 5-hydroxytryptophan.
AB  - Previous observations have shown that oral administration of 5-hydroxytryptophan
      (5-HTP) without dietary prescriptions causes anorexia, decreased food intake, and
      weight loss in obese subjects. To confirm these data over a longer period of
      observation and to verify whether adherence to dietary restriction could be
      improved by 5-HTP, 20 obese patients were randomly assigned to receive either 5
      HTP (900 mg/d) or a placebo. The study was double-blinded and was for two
      consecutive 6-wk periods. No diet was prescribed during the first period, a 5040
      kJ/d diet was recommended for the second. Significant weight loss was observed in
      5-HTP-treated patients during both periods. A reduction in carbohydrate intake
      and a consistent presence of early satiety were also found. These findings
      together with the good tolerance observed suggest that 5-HTP may be safely used
      to treat obesity.

PMID- 1384304
TI  - Electropharmacologic effects and pharmacokinetics of almokalant, a new class III
      antiarrhythmic, in patients with healed or healing myocardial infarcts and
      complex ventricular arrhythmias.
AB  - The electropharmacologic effects and pharmacokinetics of almokalant, a new class
      III antiarrhythmic, were investigated in a randomized, placebo-controlled, double
      blind study, and efficacy was evaluated. Ten post-myocardial infarction patients
      with complex ventricular arrhythmias were included and received, in randomized
      order on consecutive days, 4.5 mg (12.8 mumol) of almokalant or placebo
      intravenously over 10 minutes. One patient received infusion at a higher rate and
      developed self-terminating torsades de pointes. In the remaining 9 patients the
      corrected QT interval increased significantly: At the end of placebo infusion the
      corrected QT was 445 +/- 18 ms and after almokalant 548 +/- 53 ms (p = 0.0015).
      The signal-averaged electrocardiographic parameters did not change. The number of
      ventricular premature complexes decreased significantly during the first 15
      minutes after almokalant infusion (p = 0.04). No additional proarrhythmic or
      other significant adverse events were noted. The almokalant plasma concentration
      showed a biphasic decrease with an elimination half-life of 2.4 +/- 0.1 hours.
      Almokalant was rapidly cleared from the body with a clearance of 11 +/- 1
      ml/min/kg. When given with certain precautions almokalant appears safe and well
      tolerated and may be antiarrhythmic by prolonging refractoriness.

PMID- 1384306
TI  - Patterns of keratin 19 expression in normal, metaplastic, condylomatous,
      atrophic, dysplastic, and malignant cervical squamous epithelium.
AB  - Keratin 19 (K-19) expression has been strongly correlated with dysplasia in oral
      epithelium. Expression of K-19 was evaluated by immunoperoxidase staining in
      formalin-fixed normal ectocervical tissue, normal endocervical tissue, cervical
      dysplasia, squamous metaplasia, atrophic epithelium, cervical condylomas, and
      invasive carcinoma to determine if a correlation of K-19 expression with
      dysplasia was present in the cervical epithelium. Uniform expression of K-19 was
      seen in endocervical epithelium and in the basal layer of normal ectocervical
      epithelium in all areas where these epithelia were present. Cervical dysplasia
      without associated condylomatous changes showed increased expression of K-19 in
      suprabasal epithelium, corresponding to the level of immature cells. Squamous
      metaplasia was characterized by scattered cells with increased staining (patch
      quilt pattern). There was considerable overlap in the patterns of K-19 expression
      in dysplastic and metaplastic epithelium. Thus K-19 staining pattern could not be
      used as a distinctive marker for dysplasia in the cervical epithelium. Atrophic
      epithelium showed a characteristic uniform but low-level expression of K-19 in
      suprabasal areas. This pattern may be of diagnostic use in differentiating
      atrophic lesions from dysplasia. Condylomas showed focal loss of K-19 in the
      basal layer, suggesting induction of premature differentiation in the basal layer
      by human papillomavirus infection. Invasive carcinomas showed variable patterns.
      K-19 is a marker of immature cervical squamous epithelium, with generally
      distinctive but sometimes overlapping patterns of expression in various
      diagnostic categories.

PMID- 1384308
TI  - Radiological cases of the month. Lowe (oculocerebrorenal) syndrome.

PMID- 1384307
TI  - Follicular lymphoma of compartmentalized small cleaved center cells and mantle
      zone lymphocytes. Evidence for a common derivation.
AB  - The authors have observed a unique case of follicular lymphoma in which the
      central zones of neoplastic nodules were composed predominantly of small cleaved
      cells (SCC) that were surrounded by small lymphoid cells proliferating in wide
      mantles as in mantle zone (MZ) lymphoma. The central SCC component displayed a
      follicular SCC lymphoma-like phenotype (IgD-, CD10+, CD5-, CD68-), whereas the
      neoplastic cells of the peripheral zones had an MZ lymphoma-like phenotypic
      profile (IgD+, CD10-, CD5+, CD68+). In extranodal involved tissues, either
      follicular or diffuse (leukemic-like) patterns of lymphoma infiltration were
      noted. Flow cytometric analyses showed in the bone marrow or the peripheral blood
      two leukemic B cell populations, one mimicking the phenotypic profile (IgM+,
      IgD+, CD5+, CD10-, Leu8-) of small lymphoid cells with MZ-like features, and the
      other with phenotypic features (IgM+, IgD-, CD5+, CD10+, Leu8+) intermediate
      between those of MZ-like cells and those of the SCC component (follicular center
      like) detected in the lymph node. Immunomagnetic sorting and gene rearrangement
      studies indicated that both CD10+ and CD10- B lymphocytes and lymph node
      neoplastic B cells shared the same clonal origin. This unusual follicular
      lymphoma can be viewed as the result of the proliferation of a single follicular
      progenitor capable of differentiating toward both a germinal center and an MZ
      phenotype. The simultaneous presence in the same patient of at least three
      neoplastic B-cell populations at different maturation stages, encompassing
      follicular center and MZ phenotypes, and showing the same clonal derivation,
      indicates a close lineage relationship between follicular SCC and MZ lymphomas.

PMID- 1384309
TI  - Kindergarten readiness after extreme prematurity.
AB  - OBJECTIVE: To assess kindergarten readiness among survivors of extreme
      prematurity and to identify predictors of special education requirements. DESIGN:
      Historic cohort design. SETTING: Regionalized tertiary pediatric center.
      PARTICIPANTS: One hundred forty-nine (97%) of 153 children who were alive at
      follow-up (mean +/- SD age, 52.7 +/- 9.9 months). SELECTION PROCEDURES: Study
      cohort included infants (gestation, 23 to 28 weeks), born between 1983 and 1986
      (N = 194), who were alive at follow-up (N = 153, 79% survival). INTERVENTIONS:
      None. MEASUREMENTS AND RESULTS: Standardized neurodevelopmental and psychometric
      evaluations were administered by a multidisciplinary team that was blinded to the
      neonatal course. Thirty-one children (21%) had major neurodevelopmental
      impairments. By using the McCarthy Scales of Children's Abilities for children
      free of major impairments, 61 (63%) had one or more minor neurodevelopmental
      impairments noted. Half of the surviving children were thought to require special
      education resources at kindergarten entry. Multivariate logistic regression
      identified three significant predictors of special education: low socio-economic
      status, nonwhite race, and male gender. CONCLUSIONS: Social and demographic
      variables were associated with minor neurodevelopmental impairments and special
      education requirements among extremely premature children. Continued
      developmental follow-up and targeted interventions to reduce the risk of
      educational underachievement appear to be warranted.

PMID- 1384310
TI  - Elevated interleukin-6 and gamma-globulin during interferon therapy of hepatitis
      B.
AB  - A 49-yr-old man with chronic hepatitis B manifested hypergammaglobulinemia,
      lymphadenopathy, and a high serum interleukin-6 level following treatment with
      recombinant human alpha-interferon. One month later, when the patient was treated
      with natural beta-interferon, serum levels of interleukin-6 and gamma-globulin
      increased again. The serum gamma-globulin decreased to the pretreatment level
      after discontinuation of interferon therapy. The serum alanine aminotransferase
      level remained normal for 6 months. In this case, hypergammaglobulinemia and
      lymphadenopathy, as well as the elevated serum interleukin-6 level, were
      considered to be signs of highly enhanced humoral immunity related to alpha- and
      beta-interferon therapy.

PMID- 1384311
TI  - Immunologic markers of progression to acquired immunodeficiency syndrome are time
      dependent and illness-specific.
AB  - Since prevalent cohorts may be biased by the duration of human immunodeficiency
      virus (HIV) infection (onset bias), it is useful to assess the potential
      predictive value of markers in incident cohorts of HIV-positive subjects for whom
      the date of seroconversion is known or can reliably be estimated. Of 131
      homosexual men with HIV-1 seroconversion from New York City and Washington, DC,
      who were evaluated annually beginning in 1982, 60 developed acquired
      immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance
      of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2
      microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker
      (HIV p24 antigen) was determined using measurements made at defined time
      intervals after the known or estimated date of HIV seroconversion. When
      measurements made 3 years after seroconversion were used, all markers except anti
      p24 antibody were found to be significant estimators of AIDS risk in univariate
      analyses. In multivariate Cox regression modeling, the maximum information was
      obtained by including neopterin, interferon, and the CD4+ T-lymphocyte
      proportion. The predictive value of markers after HIV seroconversion could change
      considerably from one interval to another. Elevated levels of beta 2
      microglobulin and neopterin significantly predicted the development of Kaposi's
      sarcoma. These two markers were highly correlated (r = 0.74). The authors
      conclude that immunologic markers can be important for an HIV staging system for
      estimating prognosis and facilitating early therapeutic intervention in HIV
      positive patients.

PMID- 1384312
TI  - CD5 B lymphocyte antigen in monoclonal gammopathy.
AB  - Because B lymphocytes bearing the CD5 antigen have been involved in many B-cell
      malignancies, we have investigated the presence of the CD5 B-cell antigen on B
      and plasma cells in monoclonal gammopathy. Quantification of CD5 B cells was made
      in the peripheral blood of seven individuals with monoclonal gammopathy of
      undetermined significance (MGUS) and in that of 21 patients with multiple myeloma
      (MM). The bone marrow of ten patients with MM was also studied. Patients with
      progressive MM presented a significant reduction in both B and CD5 B lymphocytes
      (i.e., percentages and absolute numbers), when compared with individuals with
      MGUS and patients with stable MM. These latter individuals and patients did not
      differ from healthy donors. No CD5 B cells were found in the bone marrow of
      patients with MM. Moreover, no CD5 antigen could be detected on eight freshly
      established human myeloma cells lines including six totally dependent on
      interleukin-6. However, it was weakly expressed on two standard myeloma cell
      lines not requiring exogenous interleukin-6 (i.e., RPMI 8226 and U 266). In
      conclusion, our data show mainly an overall reduction of the polyclonal CD5 B
      lymphocytes similar to what is observed for the other polyclonal B lymphocytes in
      patients with active MM. Finally, the expression of the CD5 antigen human myeloma
      cell lines is not constant.

PMID- 1384313
TI  - Detecting of the minimal residual disease contaminated in peripheral blood stem
      cell transplantation in the B-cell malignant lymphoma patients.
AB  - For sufficient collection of hemopoietic stem cells from peripheral blood for
      autologous peripheral blood stem cell transplantation (PBSCT), four patients with
      B-cell-type non-Hodgkin lymphoma (B-NHL) were examined for the appearance of
      circulating hemopoietic progenitors in blood (PSC) during the hemopoietic
      recovery phase following marrow ablative therapy in combination with or without
      administration of recombinant human granulocyte colony-stimulating factor (rhG
      CSF). Each patient received only chemotherapy in the first course, and rhG-CSF (1
      microgram/kg/day) was administered for 14 consecutive days from the last day of
      the second chemotherapy. In the second chemotherapy course with rhG-CSF
      administration, white blood cell (WBC) counts demonstrated two peaks, and the
      appearance of granulocyte-macrophage precursor cells (CFU-GM) in blood at the
      maximum level was coincident with the second peak of WBC elevation. Erythroid
      precursor cells (BFU-E) were also detectable in blood after chemotherapy but the
      peak level was not enhanced by the use of rhG-CSF. To determine whether the
      minimal residual disease (MRD) cells were contaminated in PSC corrected from
      blood, kappa-lambda imaging (KLI) analysis was performed to detect the malignant
      B-cell population (mBp) before and after chemotherapy. No mBp was found in two of
      four patients in blood, although three of them were involved with mBp in bone
      marrow. The presence of mBp was detected in two patients both before and after
      chemotherapy, even though these cells were hardly detected morphologically,
      suggesting the necessity of judging for the incidence of contamination of MRD
      cells when collecting PSCs.

PMID- 1384314
TI  - Human interleukin-9 supports formation of a subpopulation of erythroid bursts
      that are responsive to interleukin-3.
AB  - We have investigated the biological activities of recombinant human interleukin-9
      (IL-9) on enriched hematopoietic progenitors, alone or in combination with other
      cytokines, including Epo, G-CSF, IL-3, and GM-CSF, under serum-containing and
      serum-free cultures. IL-9 alone did not support colony formation. However, IL-9
      plus Epo induced erythroid burst (BFU-E) formation derived from peripheral blood
      (PB) progenitors. Delayed addition experiments demonstrated that a part of bone
      marrow (BM) derived BFU-E, which seems to be immature, only responded to IL-9 and
      formed erythroid bursts. The burst-promoting activity (BPA) of IL-9 was confirmed
      using neutralizing aIL-3, aGM-CSF, and aIL-9 antisera and serum-free culture. IL
      9 supported a part of BFU-E population that respond to IL-3, which was almost
      identical to the number of BFU-E supported by GM-CSF. IL-9 had no additive effect
      on erythroid and mixed colony formation supported by IL-3. In contrast, IL-9
      showed an additive effect on erythroid burst formation supported by GM-CSF in
      serum-free culture. These data suggest that IL-9 and GM-CSF act on distinct IL-3
      responsive BFU-E population. In addition, delayed addition experiment clearly
      demonstrated that IL-9 supports survival and the early stage of proliferation of
      BFU-E. These results led us to propose that IL-9 possibly acts as a BPA and
      selectively supports a subpopulation of early class of BFU-E that respond to IL
      3.

PMID- 1384315
TI  - Black beta-thalassemia homozygotes with specific sequence variations in the 5'
      hypersensitive site-2 of the locus control region have high levels of fetal
      hemoglobin.
AB  - We have sequenced the 5' hypersensitive-2 (5'HS-2) site of the locus control
      region (LCR) and the promoters of the two gamma-globin genes located on
      chromosome 11 of a black patient with mild beta-thalassemia (beta-thal) major due
      to a homozygosity for the C----T mutation at position -88 of the beta promoter
      and with a high Hb F level. Sequence variations in the 5'HS-2 were the same as
      observed for the beta s chromosome with haplotype number 3, while most of the G
      gamma promoter and the A gamma promoter had sequences similar to that of the beta
      S chromosome with haplotype number 19. This atypical haplotype (number 19A) is
      apparently associated with an increased gamma chain production which is
      particularly evident during periods of severe hematopoietic stress. Additional
      studies on relatives of the proband and on 10 unrelated black beta-thal
      homozygotes with either the C----T mutation at -88 or the A----G mutation at -29,
      confirm the possible importance of the sequence differences in the 5'HS-2, and
      also suggest that at least two additional factors, namely a C----T mutation at
      position -158 of the G gamma promoter and a relative deficiency in alpha chain
      synthesis play a (perhaps less important) role in the increased Hb F synthesis in
      these patients.

PMID- 1384316
TI  - Human Lyb-2 homolog CD72 is a marker for progenitor B-cell leukemias.
AB  - S-HCL 2 is the prototype antibody of the recently defined CD72 cluster (human Lyb
      2). Under nonreducing conditions, S-HCL 2 monoclonal antibody (mAb) precipitates
      a glycoprotein of 80-86 kDa. Under reducing conditions, a dimer of 43 and 39 kDa,
      with core proteins of 40 and 36 kDa, is precipitated. CD72 expression in normal
      and malignant tissues is different from expression of all other previously
      described human B-cell antigens. In peripheral blood and bone marrow, the antigen
      appears to be present on all B lymphocytes, with the exception of plasma cells.
      In tissue, immunohistochemical staining revealed positivity for all known B-cell
      compartments; however, pulpa macrophages of the spleen and von Kupffer cells
      exhibited distinct positivity for CD72 also. Among 83 malignant non-Hodgkin's
      lymphomas examined by immunohistochemistry (alkaline phosphatase anti-alkaline
      phosphatase technique), all 54 B-cell lymphomas, including precursor B-cell
      lymphomas, Burkitt's lymphomas, germinal center lymphomas, chronic lymphocytic
      leukemias, and hairy cell leukemias, were CD72 positive, but no T-cell lymphomas
      were. Flow cytometry study of more than 80 mainly acute leukemias (52 B-cell
      leukemias) showed reactivity with S-HCL 2 mAb over the full range of B-cell
      differentiation. In particular, very early B cells in cytoplasmic Ig (cIg)
      negative, CD19-positive pre-pre-B-cell leukemias and hybrid leukemias (mixed
      myeloid and B-cell type) were consistently positive for CD72 on the cell surface.
      Therefore, CD72 may become an important marker for progenitor B-cell leukemias.

PMID- 1384317
TI  - Serum granulocyte colony-stimulating factor in patients with repeated infections.
AB  - We have already reported significant elevation of serum granulocyte colony
      stimulating factor (G-CSF) in the acute phase of infection. In this study, we
      compared the responses to infection between patients with frequently repeated
      infection (repeaters) and others (non-repeaters). We examined the clinical data
      and serum G-CSF levels in 48 patients with acute infections. Serum G-CSF levels
      were significantly lower in repeaters than in non-repeaters (197.7 +/- 370.0 vs.
      1014.1 +/- 924.4 pg/ml. P less than 0.001). There were no significant differences
      in age, serum total protein, or cholinesterase between the groups, but serum
      albumin was significantly lower in repeaters than in non-repeaters (2.87 +/- 0.5
      vs. 3.31 +/- 0.4 g/dl. P less than 0.005). It is suggested that administration of
      recombinant G-CSF may be useful for patients with repeated infections.

PMID- 1384318
TI  - Sequential maturation stages of monoclonal B lineage cells from blood, spleen,
      lymph node, and bone marrow from a terminal myeloma patient.
AB  - In order to fully understand the complexity of the monoclonal B lineage cells in
      multiple myeloma, it is necessary to evaluate the extent to which these cells are
      resident in solid lymphoid tissues and the phenotypic differences and
      similarities as compared to the circulating or bone marrow derived B lineage
      cells. Peripheral blood mononuclear cells from a patient with multiple myeloma
      were obtained 8 and 3 days prior to death, and mononuclear cells from lymph
      nodes, spleen, and bone marrow were obtained at autopsy. Rapid changes in the
      stage of differentiation of blood late-stage B lineage cells towards mature end
      stage plasma cells were observed during the last week prior to death. Lymphoid
      cells within the blood comprised very few T cells, sub-normal numbers of
      monocytes, and 80% of B lineage cells which were at a late stage of
      differentiation. Shortly before death, plasma cells were found in the peripheral
      blood, indicating progression to plasma cell leukemia. At autopsy, the monoclonal
      B lineage cells in lymph node, spleen, and bone marrow represented different
      stages of terminal B cell differentiation. In each tissue, the B lineage cells
      were at an earlier differentiation stage, as defined phenotypically, than the
      circulating B lineage cells found in blood 3 days prior to death. Analysis of B
      cell markers and CD45 was used to define the differentiation stage of the
      relevant B cell populations, revealing a series of differentiation stages. The
      least mature B lineage cells (CD45hi) were found in lymph node. However, the CD45
      isoform expressed was CD45R0, unlike most normal lymph node B cells. More
      differentiated B lineage cells (CD45med) were found in the bone marrow, and three
      sequential stages of pre-plasma cells were found in the spleen (CD45bright,
      CD45moderate, and CD45low-neg), all of which were CD45R0+. The B cells in normal
      spleen and bone marrow are CD45RA+. The presence of monoclonal B lineage cells in
      spleen was confirmed by Southern blotting. The B lineage cells from peripheral
      blood 3 days prior to death were approaching an end-stage plasma cell stage
      (CD45low/-). On B lineage cells from the various myeloma tissues, a concomitant
      loss of CD11b and increasing density of CD29 were observed as a function of
      progression to terminally differentiated stages.

PMID- 1384319
TI  - Autoimmune neutropenia following peripheral blood stem cell transplantation.
AB  - The differential diagnosis of unexpected neutropenia following bone marrow
      transplantation includes several potentially life-threatening complications
      including graft rejection, overwhelming infection, relapse of the underlying
      neoplasm, and intrinsic graft failure. However, a number of recent reports
      document that the differential diagnosis also includes autoimmune neutropenia,
      which, although potentially life-threatening, often responds well to
      corticosteroids or splenectomy. Autoimmune neutropenia has been reported
      following both autologous and allogeneic bone marrow transplantation. Herein we
      report a 31-year-old woman who developed a rapidly falling neutrophil count 11
      days following peripheral blood stem cell transplantation for non-Hodgkin's
      lymphoma. A laboratory evaluation supported a diagnosis of autoimmune
      neutropenia, and the neutropenia resolved following treatment with steroids and
      granulocyte-colony stimulating factor.

PMID- 1384320
TI  - Combined high-efficiency hemodialysis and charcoal hemoperfusion in severe N
      acetylprocainamide intoxication.
AB  - Several extracorporeal techniques have been used to remove N-acetylprocainamide
      (NAPA), the major metabolite of procainamide, in patients intoxicated with this
      substance. We report a patient with life-threatening NAPA intoxication who was
      rapidly and successfully treated with combined high-efficiency hemodialysis and
      charcoal hemoperfusion. The hemodialyzer and hemoperfusion cartridge were placed
      in series such that the patient's blood was dialyzed before reaching the
      cartridge. Overall clearance of NAPA was 153 mL/min, with clearance due to
      hemodialysis averaging 102 mL/min and that due to hemoperfusion averaging 88
      mL/min. Thus, addition of the hemoperfusion cartridge into the extracorporeal
      circuit resulted in a 50% increase in clearance over that obtainable by high
      efficiency hemodialysis alone. In comparison to other modalities, this technique
      is more effective than either hemodialysis or charcoal hemoperfusion alone and
      can achieve a more rapid reduction of serum NAPA levels than that observed with
      slow continuous hemofiltration or hemodiafiltration.

PMID- 1384321
TI  - Mutation analysis of the cystic fibrosis transmembrane regulator gene in Native
      American populations of the southwest.
AB  - We report DNA and clinical analyses of cystic fibrosis (CF) in two previously
      unstudied, genetically isolated populations: Pueblo and Navajo Native Americans.
      Direct mutation analysis of six mutations of the CFTR gene--namely, delta F508,
      G542X, G551D, R553X, N1303K, and W1282X--was performed on PCR-amplified genomic
      DNA extracted from blood samples. Haplotype analyses with marker/enzyme pairs
      XV2c/TaqI and KM19/PstI were performed as well. Of the 12 affected individuals
      studied, no delta F508 mutation was detected; only one G542X mutation was found.
      None of the other mutations was detected. All affected individuals have either an
      AA, AC, or CC haplotype, except for the one carrying the G542X mutation, who has
      the haplotype AB. Clinically, six of the affected individuals examined exhibit
      growth deficiency, and five (all from the Zuni Pueblo) have a severe CF
      phenotype. Four of the six Zunis with CF are also microcephalic, a finding not
      previously noted in CF patients. Our DNA data have serious implications for risk
      assessment of CF carrier status for these people.

PMID- 1384322
TI  - Molecular analysis of mutations in a patient with purine nucleoside phosphorylase
      deficiency.
AB  - Purine nucleoside phosphorylase (PNP) deficiency is an inherited autosomal
      recessive disorder resulting in severe combined immunodeficiency. The purpose of
      this study was to determine the molecular defects responsible for PNP deficiency
      in one such patient. The patient's PNP cDNA was amplified by PCR and sequenced.
      Point mutations leading to amino acid substitutions were found in both alleles.
      One point mutation led to a Ser-to-Gly substitution at amino acid 51 and was
      common to both alleles. In addition, an Asp-to-Gly substitution at amino acid 128
      and an Arg-to-Pro substitution at amino acid 234 were found in the maternal and
      paternal alleles, respectively. In order to prove that these mutations were
      responsible for the disease state, each of the three mutations was constructed
      separately by site-directed mutagenesis of the normal PNP cDNA, and each was
      transiently expressed in COS cells. Lysates from cells transfected with the
      allele carrying the substitution at amino acid 51 retained both function and
      immunoreactivity. Lysates from cells transfected with PNP alleles carrying a
      substitution at either amino acid 128 or amino acid 234 contained immunoreactive
      material but had no detectable human PNP activity. In summary, molecular analysis
      of this patient identified point mutations within the PNP gene which are
      responsible for the enzyme deficiency.

PMID- 1384323
TI  - A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: implications
      for carrier screening.
AB  - Deficiency of beta-hexosaminidase A (Hex A) activity typically results in Tay
      Sachs disease. However, healthy subjects found to be deficient in Hex A activity
      (i.e., pseudodeficient) by means of in vitro biochemical tests have been
      described. We analyzed the HEXA gene of one pseudodeficient subject and
      identified both a C739-to-T substitution that changes Arg247----Trp on one allele
      and a previously identified Tay-Sachs disease mutation on the second allele. Six
      additional pseudodeficient subjects were found to have the C739-to-T mutation.
      This allele accounted for 32% (20/62) of non-Jewish enzyme-defined Tay-Sachs
      disease carriers but for none of 36 Jewish enzyme-defined carriers who did not
      have one of three known mutations common to this group. The C739-to-T allele,
      together with a "true" Tay-Sachs disease allele, causes Hex A pseudodeficiency.
      Given both the large proportion of non-Jewish carriers with this allele and that
      standard biochemical screening cannot differentiate between heterozygotes for the
      C739-to-T mutations and Tay-Sachs disease carriers, DNA testing for this mutation
      in at-risk couples is essential. This could prevent unnecessary or incorrect
      prenatal diagnoses.

PMID- 1384324
TI  - Pelizaeus-Merzbacher disease: detection of mutations Thr181----Pro and Leu223---
      Pro in the proteolipid protein gene, and prenatal diagnosis.
AB  - A family with an apparent history of X-linked Pelizaeus-Merzbacher disease
      presented for genetic counseling, requesting carrier detection and prenatal
      diagnosis. RFLP analysis using the proteolipid protein (PLP) gene probe was
      uninformative in this family. A prenatal diagnosis on a chorionic villus sample
      (CVS) was carried out using single-strand conformation polymorphism (SSCP)
      analysis of a variant in exon 4 of the PLP gene. The fetus was predicted to be
      unaffected. Sequencing of the exon from the CVS, the predicted-carrier mother,
      and the obligate-carrier grandmother revealed an A-to-C change at nucleotide 541
      in the two women but not in the fetus. As this change results in a Thr-to-Pro
      change at amino acid 181 in a region of the gene predicted to be part of a
      transmembrane segment, it was concluded that this was the mutation causing the
      disease in this family. In addition, in a second family, an exon 5 variant band
      pattern on SSCP analysis was shown by sequencing to be due to a T-to-C change at
      nucleotide 668. This results in a Leu-to-Pro change in a carrier mother and in
      her two affected sons. These results provide further examples of mutations in PLP
      that cause Pelizaeus-Merzbacher disease and illustrate the value of SSCP in
      genetic analysis.

PMID- 1384325
TI  - Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene
      account for a continuous range of phenotypes in human piebaldism.
AB  - Piebaldism is a rare autosomal dominant disorder of pigmentation, characterized
      by congenital patches of white skin and hair from which melanocytes are absent.
      We have previously shown that piebaldism can result from missense and frameshift
      mutations of the KIT proto-oncogene, which encodes the cellular receptor tyrosine
      kinase for the mast/stem cell growth factor. Here, we report two novel KIT
      mutations associated with human piebaldism. A proximal frameshift is associated
      with a mild piebald phenotype, and a splice-junction mutation is associated with
      a highly variable piebald phenotype. We discuss the apparent relationship between
      the predicted impact of specific KIT mutations on total KIT-dependent signal
      transduction and the severity of the resultant piebald phenotypes.

PMID- 1384326
TI  - Missense variations in the cystic fibrosis gene: heteroduplex formation in the
      F508C mutation.

PMID- 1384327
TI  - Cystic fibrosis genotypes and views on screening are both heterogeneous and
      population related.

PMID- 1384328
TI  - Screening for five mutations detects 97% of cystic fibrosis (CF) chromosomes and
      predicts a carrier frequency of 1:29 in the Jewish Ashkenazi population.
AB  - To determine the distribution and frequency of cystic fibrosis (CF) mutations in
      the Israeli population, we have screened 96 patients for 11 relatively common
      mutations. Five mutations--delta F508, G542X, W1282X, N1303K, and 3849 + 10kb C-
      >T--were found to account for 97% of the CF alleles in the Ashkenazi Jews. In
      contrast, of the 11 mutations tested, only delta F508 was detected in Jewish
      patients of Sephardic or Oriental origin, accounting for 43% of the CF alleles.
      Four mutations--delta F508, G542X, W1282X, and N1303K--accounted for 55% of the
      CF alleles in Arab patients. In a pilot screening study, a random sample of 424
      Ashkenazi individuals was analyzed for three mutations--delta F508, W1282X, and
      G542X. Thirteen individuals were detected as heterozygotes (six for delta F508
      and seven for W1282X), predicting a heterozygote frequency of 1:29. This is
      similar to the frequency of carriers in the Caucasian population of northern
      European ancestry. On the basis of these data, the Ashkenazi population is
      considered to be a candidate for CF heterozygote screening.

PMID- 1384329
TI  - A molecular deletion of distal chromosome 4p in two families with a satellited
      chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.
AB  - We report two families with a satellited chromosome 4 short arm (4ps). Satellites
      and stalks normally occur on the short arms of acrocentric chromosomes; however,
      the literature cites several reports of satellited nonacrocentric chromosomes,
      which presumably result from a translocation with an acrocentric chromosome. This
      is the first report of 4ps chromosomes. Our families are remarkable in that both
      unaffected and affected individuals carry the 4ps chromosome. The phenotypes
      observed in affected individuals, although dissimilar, were sufficient to
      encourage a search for a deletion of chromosome 4p. By Southern blot analysis and
      fluorescence in situ hybridization, a deletion of material mapping approximately
      150 kb from chromosome 4pter was discovered. This deletion is notable because it
      does not result in the Wolf-Hirschhorn syndrome and can result in an apparently
      normal phenotype. We speculate that homology between subterminal repeat sequences
      on 4p and sequences on the acrocentric short arms may explain the origin of the
      rearrangement and that position effect may play a role in the expression of the
      abnormal phenotype.

PMID- 1384330
TI  - Case report: role of granulocyte colony stimulating factor in radiotherapy.
AB  - Two patients who received granulocyte colony stimulating factor (G-CSF) before or
      during radiotherapy are reviewed. Both patients developed granulocytopenia after
      multi-agent chemotherapy. One patient had breast cancer with multiple distant
      metastasis and received palliative radiotherapy to the spine and hip joint. The
      other patient had locally advanced anal carcinoma and received concurrent 5
      fluorouracil, mitomycin, and radiation therapy. Both patients completed the
      planned course of radiotherapy without interruption, after administration of G
      CSF.

PMID- 1384331
TI  - Unilateral radio-ulnar synostosis, generalized hypotonia, developmental
      retardation, and a characteristic facial appearance in sibs: a new syndrome.
AB  - We report on 2 sibs with generalized hypotonia, developmental retardation,
      unilateral radio-ulnar synostosis, and a characteristic facial appearance. We
      propose that they have a new autosomal recessive syndrome.

PMID- 1384332
TI  - Multiple-marker screening in pregnancies with hydropic and nonhydropic Turner
      syndrome.
AB  - OBJECTIVE: The combination of maternal serum alpha-fetoprotein, unconjugated
      estriol, and human chorionic gonadotropin levels and maternal age has been used
      to increase the sensitivity of screening for fetal Down syndrome and trisomy 18
      in early-second-trimester pregnancies. We hypothesized that a unique pattern of
      these analytes also may be characteristic of fetal Turner syndrome, with or
      without hydrops. STUDY DESIGN: We studied preamniocentesis, second-trimester
      maternal serum specimens from seven hydropic and eight nonhydropic cases of fetal
      Turner syndrome. Clinical and pathologic records were reviewed. Statistical
      analysis of the data was performed by the rank sum test. RESULTS: In both
      hydropic and nonhydropic cases, alpha-fetoprotein levels were slightly reduced,
      and unconjugated estriol levels were markedly reduced. In hydropic pregnancies
      human chorionic gonadotropin levels were elevated, and nonhydropic pregnancies
      had low human chorionic gonadotropin levels (p = 0.001). CONCLUSIONS: The results
      suggest that the morphologic defect of hydrops, rather than the aneuploidy
      itself, is responsible for the elevation in human chorionic gonadotropin. In
      conjunction with the low unconjugated estriol levels, the elevation in human
      chorionic gonadotropin levels will result in the prenatal identification of
      hydropic fetal Turner syndrome pregnancies as being at increased risk for fetal
      Down syndrome.

PMID- 1384333
TI  - Elevated maternal serum alpha-fetoprotein levels and midtrimester placental
      abnormalities in relation to subsequent adverse pregnancy outcomes.
AB  - OBJECTIVE: Unexplained elevations of maternal serum alpha-fetoprotein levels in
      the second trimester of pregnancy are associated with adverse pregnancy outcomes,
      including intrauterine growth retardation, preterm delivery, preeclampsia, and
      abruptio placentae. In addition, elevations of maternal serum alpha-fetoprotein
      have been associated with placental lesions detected during second-trimester
      ultrasonographic evaluations. We examined the relationship between adverse
      pregnancy outcomes and unexplained elevations of maternal serum alpha-fetoprotein
      and placental abnormalities in the second trimester of pregnancy. STUDY DESIGN:
      During the period from January 1989 to March 1991 we conducted a cohort study of
      201 women with an elevated maternal serum alpha-fetoprotein (> or = 2.0 multiples
      of the median) and a second-trimester ultrasonographic evaluation at Swedish
      Hospital Medical Center and 211 women with normal maternal serum alpha
      fetoprotein levels who had also undergone ultrasonographic evaluation at the same
      institution. All women in this investigation had singleton pregnancies without
      fetal anomalies. RESULTS: Elevated maternal serum alpha-fetoprotein was
      associated with the following adverse pregnancy outcomes: low birth weight
      (adjusted risk ratio 3.7), preterm delivery (adjusted risk ratio 3.6),
      intrauterine growth retardation (adjusted risk ratio 4.0), preeclampsia (adjusted
      risk ratio 3.8) and abruptio placentae (adjusted risk ratio 4.8). Placental
      abnormalities detected during second-trimester ultrasonographic evaluations were
      also associated with adverse pregnancy outcomes: low birth weight (adjusted risk
      ratio 2.0), preterm delivery (adjusted risk ratio 2.3), intrauterine growth
      retardation (adjusted risk ratio 1.4), and abruptio placentae (adjusted risk
      ratio 9.0). A joint positive history of second-trimester elevations of maternal
      serum alpha-fetoprotein and placental abnormalities was more strongly associated
      with the following adverse infant outcomes: low birth weight (adjusted risk ratio
      6.9), preterm delivery (adjusted risk ratio 5.6), and intrauterine growth
      retardation (adjusted risk ratio 5.3). CONCLUSIONS: Unexplained elevated levels
      of maternal serum alpha-fetoprotein and placental abnormalities detected in the
      second trimester of pregnancy are associated with particularly poor pregnancy
      outcome. Careful examination for placental abnormalities should be part of the
      evaluation of elevated maternal serum alpha-fetoprotein.

PMID- 1384334
TI  - Comparison of gram stain, leukocyte esterase activity, and amniotic fluid glucose
      concentration in predicting amniotic fluid culture results in preterm premature
      rupture of membranes.
AB  - OBJECTIVE: The purpose of this study was to prospectively compare three rapid and
      inexpensive tests that have been proposed as predictors of amniotic fluid culture
      results in preterm premature rupture of membranes. STUDY DESIGN: Amniocentesis
      was performed on 117 patients < or = 34 weeks' gestational age with premature
      rupture of membranes and no clinical evidence of infection. Amniotic fluid was
      sent for Gram stain and aerobic, anaerobic, and Mycoplasma cultures. Leukocyte
      esterase activity and glucose concentration were also determined on the amniotic
      fluid. RESULTS: Amniotic fluid cultures were positive in 56 patients (47.8%).
      Leukocyte esterase activity of 1+ or 2+ and an amniotic fluid glucose
      concentration < or = 16 mg/dl were significantly more sensitive (p < 0.005) than
      Gram stain in detecting positive amniotic fluid cultures (73%, 68%, and 41%,
      respectively). CONCLUSIONS: Although each of these rapid tests is useful in
      assessing for subclinical intraamniotic infection, none of them have sufficient
      accuracy to make clinical decisions solely on the basis of their results.

PMID- 1384335
TI  - Midtrimester pregnancy termination: a randomized trial of prostaglandin E2 versus
      concentrated oxytocin.
AB  - OBJECTIVES: The purpose of this study was to determine whether a concentrated
      oxytocin infusion can reliably effect uterine evacuation in the midtrimester and
      whether such an infusion is associated with fewer side effects than prostaglandin
      E2 vaginal suppositories. STUDY DESIGN: Patients received either prostaglandin E2
      (n = 42) or oxytocin (n = 45) for indicated midtrimester abortions in a
      prospective, randomized trial. Treatment consisted of either prostaglandin E2
      vaginal suppositories (one every 4 hours) or infusions of an escalating
      concentration of oxytocin (one every 4 hours). Unless delivery had occurred or
      was imminent after 24 hours, the agent was considered to have failed, and
      patients were crossed to the alternative method. RESULTS: Delivery indications
      were similar between the two groups. There were 6 (14%) first-agent failures with
      prostaglandin E2 and 9 (20%) with oxytocin (p = 0.48). Considering the failures
      and subsequent crossovers, 103 patient trial regimens were completed. Fever,
      nausea, vomiting, and diarrhea were more frequent with prostaglandin E2 (p <
      0.005). CONCLUSIONS: Concentrated oxytocin is a satisfactory alternative to
      prostaglandin E2 for midtrimester abortion.

PMID- 1384336
TI  - Behr's syndrome and 3-methylglutaconic aciduria.
AB  - We examined three patients from two families of Jewish-Iraqi origin who had
      progressive reduction of visual acuity and childhood onset of bilateral optic
      nerve atrophy without additional retinal abnormalities. They had neurologic
      symptoms compatible with Behr's syndrome. Neurologic signs included increased
      tendon reflexes, a positive Babinski sign, progressive spastic paraplegia,
      dysarthria, head nodding, and horizontal nystagmus. Neurologic involvement varied
      between affected siblings. The patients excreted excessive amounts of 3
      methylglutaconic acid and 3-methylglutaric acid in their urine. We compared the
      characteristic ophthalmic features and the spectrum of neurologic signs
      encountered in this recently delineated autosomal recessive clinical entity with
      those of previously described entities associated with 3-methylglutaconic
      aciduria. Patients with early-onset optic atrophy should be examined for
      neurologic signs and screened for organic aciduria. A detailed ophthalmic
      examination is important in patients with neurologic abnormalities compatible
      with Behr's syndrome.

PMID- 1384337
TI  - CD5 monoclonal antibodies react with human peripheral blood dendritic cells.
AB  - CD5 monoclonal antibodies (MAbs) define a 67,000 kd monomeric glycoprotein
      expressed predominantly by thymocytes, mature T cells and a subpopulation of B
      cells. CD5 is believed to be an alternative signaling molecules capable of
      increasing the supply of second messengers and thereby altering the cellular
      response threshold to other activation stimuli. Human peripheral blood dendritic
      cells (PBDC) are a circulating component of the immune dendritic cell family,
      which also includes Langerhans' cells in epithelia and interdigitating cells in
      the T-cell domains of lymphoid tissues. PBDC comprise less than 1% of the
      peripheral blood mononuclear cell fraction. They are morphologically,
      immunophenotypically, and functionally distinct from monocytes. In this study, we
      report that at least a subpopulation of PBDC react with the anti-CD5 MAbs Leu-1
      and UCHT2, which define the two major non-crossblocking CD5 epitopes. In
      contrast, Langerhans' cells, interdigitating cells, monocytes, and macrophages
      were uniformly CD5-. These findings suggest that PBDC can express the CD5
      molecule. Furthermore, they define an additional feature of many enriched PBDC
      that distinguishes them from monocytes and certain other mononuclear leukocytes,
      and may provide insights into their activation pathways.

PMID- 1384339
TI  - Role of beta 1-integrins in epidermotropism of malignant T cells.
AB  - To better understand the molecular mechanisms of epidermotropism, we
      immunohistochemically analyzed the expression pattern of adhesion molecules
      belonging to the integrin and immunoglobulin superfamilies in cases of mycosis
      fungoides (MF) (n = 15), pleomorphic T cell lymphoma (n = 10), and high-grade T
      cell lymphoma (n = 7). The cutaneous T cell lymphomas (CTCLs) investigated were
      categorized into cases with or without epidermotropism. Focal neoexpression of
      ICAM-1 on keratinocytes was restricted to epidermotropic lymphomas. Both LFA-1
      and LFA-3 were expressed on infiltrating cells in all cases investigated. In
      contrast, beta 1-integrins showed differential expression, most prominent in the
      case of VLA-1 and VLA-6: These molecules were present on infiltrating cells in
      most cases with epidermotropic MF and absent in most other CTCLs. We conclude
      that the phenomenon of epidermotropism might involve different sets of adhesion
      molecules in different entities of CTCL, with VLA-1 being the most influential
      beta 1-integrin in the case of MF.

PMID- 1384338
TI  - Markers for dysplasia of the upper aerodigestive tract. Suprabasal expression of
      PCNA, p53, and CK19 in alcohol-fixed, embedded tissue.
AB  - Recognition of premalignant lesions in the oral epithelium has the potential to
      increase survival rates for squamous cell carcinoma of the oral cavity. It has
      previously been reported that cytokeratin 19 (CK19), a 40-kd epithelial
      cytoskeletal protein within the suprabasal squamous epithelium, is a specific
      marker of moderate-to-severe dysplasia and carcinoma in situ in oral cavity
      squamous epithelium. In contrast, normal epithelium and hyperplastic lesions
      reportedly express CK19 only in the basal layer if at all. The authors chose to
      test and extend this hypothesis by studying suprabasal CK19 expression and
      dysplasia of the oral cavity and upper aerodigestive tract in paraffin-embedded
      specimens that had been fixed in alcohol, a superior fixative for the
      preservation of cytokeratins. The authors examined 56 alcohol-fixed, paraffin
      embedded specimens including 37 from the oral cavity, using two antibodies
      specific for CK19 (Ks19.1 and 4.62), an antibody to the nuclear proliferation
      marker, proliferating cell nuclear antigen (PCNA) (19A2), and an antibody to the
      putative tumor suppressor gene, p53 (pAb1801). The lesions were classified as
      normal, hyperplasia, mild dysplasia, moderate dysplasia, severe
      dysplasia/carcinoma in situ, or invasive squamous cell carcinoma, following
      standard histologic criteria. Immunocytochemically stained sections were scored
      for the presence or absence of suprabasal CK19, suprabasal PCNA, and p53
      positivity, regardless of location. The immunostaining patterns of the two anti
      CK19 antibodies were essentially equivalent. Except for one laryngeal specimen,
      normal epithelium, when positive, showed CK19 expression only in scattered cells
      throughout the basal layer. Proliferating cell nuclear antigen-positive nuclei
      were found exclusively in the basal layer. In areas of hyperplasia, CK19
      immunostaining was absent or confined to the basal layer in 20 of 38 specimens
      and was expressed in suprabasal cells in 18 of 38 hyperplastic specimens.
      Proliferating cell nuclear antigen immunostaining in all cases of hyperplasia was
      limited to the basal layer. Severe dysplasia and carcinoma in situ showed
      suprabasal CK19 staining in six of nine specimens and no CK19 staining in three
      of nine specimens. In contrast, suprabasal PCNA immunostaining was found in all
      dysplasia and carcinoma in situ cases. p53 expression was detected in three of
      nine severe dysplasia/CIS specimens and was immunocytochemically undetectable in
      all normal, hyperplasia, and mild to moderate dysplasia specimens. The authors
      conclude that suprabasal CK19 expression is neither a sensitive nor a specific
      marker of premalignancy in oral epithelium and cannot be used to distinguish
      hyperplasia from dysplasia. In contrast, a strong correlation between suprabasal
      expression of PCNA, a marker for proliferating cells, and dysplasia/carcinoma in
      situ was evident.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1384340
TI  - Enhanced tenascin expression in cervical and vulvar koilocytotic lesions.
AB  - Tenascin is an extracellular matrix glycoprotein that is widely expressed during
      embryogenesis. In adults, it is restricted to select sites, including certain
      epithelial-stromal interfaces, but is notably enhanced in active inflammatory
      reactive processes and in the stroma of many neoplasms. The authors immunostained
      with the monoclonal antibody (MAb) 100EB2 cryosections of vulvar and cervical
      biopsies displaying convincing koilocytosis with variable degrees of hyperplasia
      dysplasia; in situ carcinomas were included. The presence of human
      papillomaviruses (HPV) 6, 11, 16, 18, 31, or 33 was confirmed by in situ
      hybridization in a subset of cases. Findings were compared with normal controls.
      The study was extended with the MAb 143DB7 that reacted with tenascin in paraffin
      sections. In normal samples, tenascin immunoreaction appeared as a delicate,
      continuous rim, in the immediate vicinity of the laminin staining; in
      parakeratotic areas, the rim was thicker. In foci of hyperplastic-dysplastic
      epithelium with or without koilocytosis, a distinct increase in tenascin staining
      was noted; enhanced tenascin often paralleled increasing hyperplasia and
      dysplasia. In most cervical and vulvar carcinomas in situ, the reactions were
      intense and extended deeply and raggedly into the underlying stroma. Tenascin was
      selectively enhanced in the endocervical stroma around inflammed or metaplastic
      glands. The authors conclude that tenascin is increased in HPV infection
      associated with epithelial proliferation. Enhancement was most consistently
      strong and extensive in in situ carcinomas, suggesting a correlation with active
      phases of epithelial growth and stromal remodeling.

PMID- 1384341
TI  - Nuclear translocation of monoclonal antibody directed against cell-surface
      carbohydrate Y determinant.
AB  - Monoclonal antibody (MAb) Br 15-6A directed against the carbohydrate Y
      determinant expressed on tumor cells was found to be internalized and
      translocated to the nucleus of SK Br 5 breast carcinoma and SW 1116 and SW 707
      colorectal carcinoma cells. Intracellular localization of MAb Br 15-6A was
      determined by cell fraction and by indirect immunofluorescence staining.
      Internalization of MAb Br 15-6A seems to be mediated by a specific cell surface
      protein of M(r) 108,000 in colorectal carcinoma cells and M(r) 92,000-96,000 in
      breast carcinoma cells. The MAb Br 15-6A precipitates an 88,000 M(r) chromatin
      protein and appears to be bound specifically to two EcoRI-digested and two HincII
      chromatin fragments. Another MAb against the Y determinant (MAb Br 55.2)
      recognizes the same antigens as MAb Br 15-6A, but is not internalized.

PMID- 1384343
TI  - Possible role of interleukin 1 alpha and interleukin 1 beta in the pathogenesis
      of cholesteatoma of the middle ear.
AB  - Cholesteatoma of the middle ear is characterized by the presence of
      hyperproliferative keratinizing squamous epithelium in the middle ear cavity and
      destruction of adjacent bone. Interleukin 1 (IL-1) is an autocrine growth factor
      for normal keratinocytes and is capable of inducing bone degradation. The
      distribution of two molecular species of IL-1, IL-1 alpha and IL-1 beta, was
      investigated immunohistochemically in the hyperproliferative epithelium of
      cholesteatoma, in normal epidermis of the auditory canal and of the
      retroauricular region, and in nonkeratinizing tonsillar epithelium. In all
      squamous epithelia examined, IL-1 alpha and IL-1 beta were present in comparable
      amounts. The IL-1 content of cholesteatoma epithelium was clearly increased in
      relation to normal skin keratinocytes. All cellular layers of cholesteatoma
      epithelium stained strongly and uniformly for Il-1 alpha and IL-1 beta, whereas
      the keratin layer was negative for IL-1. No particularly strong reaction with
      basal cells was detected. In the connective tissue under the squamous epithelium
      of cholesteatoma, intensely positive cells were scattered between negative
      stromal cells. Our results suggest that IL-1 could be liberated from
      disintegrating keratinocytes and cells of the monocyte-macrophage lineage,
      stimulate the proliferation of the cholesteatoma epithelium in an autocrine
      manner, and contribute to the enhancement of bone destruction in the presence of
      cholesteatoma.

PMID- 1384342
TI  - Continuous secretion of monocyte chemotactic factors and fibroblast growth
      factors by alveolar macrophages following a single exposure to bleomycin in
      vitro.
AB  - It has been shown in previous studies that alveolar macrophages incubated with
      bleomycin in vitro for 2 to 18 hours secrete monocyte chemotactic factors and
      fibroblast growth factors (MDGF). The purpose of the current experiments was to
      determine if alveolar macrophages similarly stimulated with bleomycin would
      continue to secrete these factors once the stimulus was removed. Alveolar
      macrophages from normal rats were exposed to bleomycin for 18 hours after which
      bleomycin was removed and macrophages maintained in culture for 35 days.
      Conditioned medium (CM) was collected and assayed at weekly intervals. In
      comparison with nonstimulated controls, bleomycin-stimulated macrophages secreted
      greater amounts of both monocyte chemotactic factors and MDGF for 35 days after
      exposure to bleomycin; with a significant difference noted between bleomycin and
      control macrophages for the first 21 days (P less than 0.02). In agreement with
      past work, the chemotactic activity in bleomycin-CM was due to fibronectin, as
      evidenced by the almost complete inhibition of activity by anti-fibronectin
      antibodies. The time course of secretion of chemotactic and growth factors after
      a single exposure to bleomycin in vitro was similar to that induced by in vivo
      exposure of macrophages to this drug. The data suggest that a similar direct
      activation of macrophages by bleomycin may promote the long-term production of
      these factors in vivo, resulting in continued monocyte recruitment and promotion
      of fibroblast proliferation in fibrotic lungs.

PMID- 1384344
TI  - Fetuin: its enigmatic property of growth promotion.
AB  - A variety of cell types in culture respond to fetuin, a glycoprotein from fetal
      bovine serum, which is often an important supplement to many serum-free media.
      Bovine fetuin preparation has been shown to inhibit trypsin activity and promote
      cellular attachment, growth, and differentiation in many different culture
      systems. In addition, fetuin associates with various growth factors or growth
      promoting substances. However, whether the growth-promoting activity of fetuin
      preparation is due to fetuin per se or to its minor contaminant(s) has been a
      long-standing puzzle. The present review surveys the literature concerning this
      enigmatic property of fetuin and summarizes three possibilities: 1) fetuin itself
      is active, although the majority of studies do not support this; 2) various
      contaminants of fetuin preparations, including potentially unidentified ones, are
      responsible for the activity, a possibility supported by numerous reports; and 3)
      one of the fetuin subspecies, one of its contaminants, or a combination of both
      of these is responsible for growth of a specific cell type. In addition, the
      basic physicochemical properties and other biological functions of fetuin have
      also been presented.

PMID- 1384345
TI  - The iodide channel of the thyroid: a plasma membrane vesicle study.
AB  - The uptake of radioactive iodide or chloride by plasma membrane vesicles of
      bovine thyroid was studied by a rapid filtration technique. A Na(+)-I-
      cotransport was demonstrated. When this Na(+)-I- cotransport is inactive (i.e.,
      at 4 degrees C and in the absence of Na+), an uptake of iodide above chemical
      equilibrium could be induced, driven by the membrane potential. The latter was
      set up by allowing potassium to diffuse into the membrane vesicles in the
      presence of valinomycin and of an inward K+ gradient. This potential difference
      (positive inside) induced the uptake of iodide (or other anion present). The data
      support the existence of two anionic channels. The first one, observed at low
      near-physiological iodide concentration (micromolar range), which exhibits a high
      permeability and specificity for iodide (hence called the iodide channel), has a
      Km of 70 microM. The other one appears similar to the epithelial anion channel as
      described by Landry et al. (J. Gen. Physiol. 90: 779-798, 1987); it is still
      about fourfold more permeable to iodide than to chloride and presents a Km of 33
      mM. Under physiological conditions the latter channel would mediate chloride
      transport, and the iodide channel, which is proposed to be restricted to the
      apical plasma membrane domain of the thyrocyte, transports iodide from the
      cytosol to the colloid space.

PMID- 1384346
TI  - Evidence for an InsP3-gated channel protein in isolated rat olfactory cilia.
AB  - Stimulation of rat olfactory cilia (ROC) with odorants leads to a transient
      elevation in the levels of either cAMP or inositol trisphosphate (InsP3). We have
      characterized the binding of [3H]InsP3 to isolated ROC. Unlabeled InsP3 displaced
      [3H]InsP3 binding in a dose-dependent manner (dissociation constant = 3.9 +/-
      0.65 microM). Binding was stereospecific and dependent on the number of
      phosphates in the inositol ring. A ciliary protein of 120 kDa molecular mass was
      labeled specifically upon exposure of cilia membranes to ultraviolet light in the
      presence of the 125I-labeled InsP3 analogue 1-O-[N-(4-azidosaliciloxy)-3
      aminopropyl-1-phospho]-myo-inositol 4,5-bisphosphate. Labeling of this protein
      displayed the same stereospecificity as binding of [3H]InsP3 to ROC. In addition,
      ROC membranes incorporated into a phospholipid bilayer at the tip of a patch
      pipette displayed an increase in conductance upon exposure to micromolar D
      myoinositol 1,4,5-trisphosphate in 45% of the trials (n = 88). The InsP3-gated
      conductance is relatively nonspecific for cations and is distinct from the cAMP
      gated conductance. The conductance displayed stereospecificity consistent with
      the InsP3 binding experiments. The results suggest that the site of action for
      odorant-stimulated elevations in InsP3 concentration in rat olfactory cilia is at
      a ciliary InsP3-gated channel.

PMID- 1384347
TI  - Small linear chloride channels are endogenous to nonepithelial cells.
AB  - We used both single-channel and whole cell patch-clamp techniques to characterize
      chloride channels and currents endogenous to Sf9 cells, 3T3 fibroblasts, and
      Chinese hamster ovary cells. In cell-attached patches from these cell types,
      anion channels were observed with low ohmic conductance (4-11 ps), linear current
      voltage relationships, and little time- or voltage-dependent behavior. These
      channels are very similar to the Cl- channels reported to appear concomitant with
      the expression of cystic fibrosis transmembrane conductance regulator (CFTR) in
      these cell lines. The presence of such endogenous channels suggests either that
      low levels of CFTR are present in all of these cell lines prior to transfection
      or that an endogenous non-CFTR channel is present in these cell types. Our
      results suggest that at least some of the channel behaviors attributed to
      expressed, recombinant CFTR in previous studies may have been due to these
      endogenous Cl- channels.

PMID- 1384348
TI  - Epitope mapping of monoclonal antibodies to bovine prolactin.
AB  - The epitopes recognized by three monoclonal antibodies generated to sheep
      prolactin were determined by evaluating their cross-reactivities by immunodot
      analysis with 14 mutants of bovine prolactin, in which individual amino acids had
      been deleted or substituted. Mutations were made throughout the molecule and
      included disruption of the amino-terminal, carboxyl-terminal, and central
      disulfide loops. Lack of immunoreactivity was taken as an indication that the
      site of mutation was part of the epitope. Antibody 6F11 reacted with all bovine
      prolactin mutants tested, except those in which the carboxyl-terminal cysteine
      (position 199) was substituted by a serine. Antibodies 5G2 and 4C10 reacted with
      all of the bovine prolactin mutants, except those in which the amino-terminal
      cysteine (position 4) was substituted by a serine. Western blot analysis of
      sheep, squirrel monkey, and rat prolactins with the monoclonal antibodies
      revealed that 5G2 and 4C10 were specific for sheep prolactin, whereas antibody
      6F11 cross-reacted with prolactins from all three species. The mitogenic activity
      of sheep or rat prolactin in the Nb2 bioassay was determined in the presence of
      the antibodies to determine whether the epitopes were part of the functional
      domains of these prolactins. The bioactivity of sheep prolactin (0.4 ng/ml) was
      unaffected by the monoclonal antibodies [0.01-1 microgram immunoglobulin G
      (IgG)/ml], whereas the bioactivity of rat prolactin (1.25 ng/ml) was inhibited by
      6F11 with an apparent 50% inhibitory concentration of 0.25 microgram IgG/ml.
      These results indicate that monoclonal antibodies 5G2 and 4C10 cross-react with a
      species-specific region of the amino-terminal disulfide loop of bovine
      prolactin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384349
TI  - Expression and localization of GLUT-5 in Caco-2 cells, human small intestine, and
      colon.
AB  - The human colon carcinoma cell line Caco-2 was used as an enterocyte model to
      study the expression of the facilitative glucose transporters GLUT-1 and GLUT-2,
      and of the putative hexose transporter GLUT-5, which are expressed specifically
      in the gut. Northern blots indicate that Caco-2 cells express GLUT-1 and GLUT-5
      mRNAs but not the mRNA coding for the basolateral glucose transporter GLUT-2. The
      level of GLUT-5 mRNA is growth dependent, being detectable only in postconfluent
      differentiated cells. In addition, the expression of GLUT-5 increases with the
      number of cell passages and is approximately 10 times higher in later passages
      (passage 184) than in early ones (passage 26). With the use of polyclonal
      antibodies directed against the COOH-terminus of GLUT-5, indirect
      immunofluorescence and Western blotting indicate that GLUT-5 is mainly localized
      to the brush border of Caco-2 cells. GLUT-5 is also found to be associated with
      the brush border of epithelial cells from fetal and normal adult human small
      intestine, but is absent from the colon.

PMID- 1384350
TI  - Mechanism of action of cholecystokinin octapeptide on cat lower esophageal
      sphincter.
AB  - In five cats we examined 1) the role of a cholinergic mechanism in
      cholecystokinin octapeptide (CCK-OP) excitation of the lower esophageal sphincter
      (LES) and 2) the interaction between CCK-OP-induced excitation and inhibition of
      the LES. Under ketamine anesthesia, LES pressure was monitored with a sleeve
      catheter. With CCK-OP, LES excitation was seen in four of five cats, and
      inhibition was seen in three of five cats. (4-Hydroxy-2-butynyl)trimethylammonium
      chloride (McNeil-A343) produced similar responses in the same cats but was less
      potent than CCK-OP. Atropine and/or hexamethonium reduced the response to CCK-OP.
      Pirenzepine had no effect on any CCK-OP response but reduced relaxation and
      enhanced excitation produced by McNeil-A343. Phentolamine increased CCK-OP
      induced relaxation. In conclusion, CCK-OP can produce LES contraction through a
      preganglionic cholinergic mechanism involving a nicotinic synapse; however,
      induction of relaxation occurs predominantly at a postganglionic site involving
      adrenergic modulation. There is animal-to-animal variability in the balance of
      excitatory and inhibitory mechanisms to the LES, which determines the effect of a
      drug capable of activating both mechanisms.

PMID- 1384351
TI  - Oxygen affects human endothelial cell proliferation by inactivation of fibroblast
      growth factors.
AB  - The fibroblast growth factors (FGF), including endothelial cell growth factor
      (ECGF)/acidic FGF and basic FGF, are important modulators of endothelial cell
      replication in vitro and in vivo. Premature infants and adults with lung injuries
      are often treated with high levels of inspired O2, which can be necessary for
      survival but potentially injurious to developing lungs and in tissue repair
      following injury. Human umbilical artery and vein endothelial cells were grown in
      ECGF- or FGF-supplemented Medium 199 and exposed to ambient levels of O2 from 10
      to 95%. Endothelial cell growth, measured by [3H]thymidine incorporation, was
      inhibited by increasing levels of O2 and ceased above 50% O2. Vein endothelial
      cells could recover from up to 24 h of hyperoxic exposure when given fresh
      medium, but not after 48 h. Artery-derived cells were more sensitive to O2 than
      were vein-derived cells. Complete medium without endothelial cells, preincubated
      24 h in 95% O2, lost its ability to support cell growth under normoxic
      conditions. Exposing individual medium components to high O2 demonstrated that
      purified natural ECGF and recombinant acidic or basic FGF were all inactivated by
      O2. Human recombinant superoxide dismutase prevented FGF inactivation. O2
      inactivation of essential growth factors could thus have major consequences for
      lung development or repair of injured capillaries in infants or adults inspiring
      high levels of O2.

PMID- 1384352
TI  - The effect of dietary fat on diet selection may involve central serotonin.
AB  - Rats consuming a diet of 34% tallow select more protein and less carbohydrate
      than rats fed either 5% corn oil or tallow or 34% corn oil (25). To examine
      potential mechanism(s) of this phenomenon, we fed rats diets containing either
      tallow or corn oil at levels of 5 or 34% for 2 days. Sera were analyzed, and rats
      fed 34% tallow had higher serum insulin compared with those fed 34% corn oil. In
      a second experiment, rats were fed either 34% corn oil or tallow for 2 days.
      Brain tissues were analyzed, and rats fed 34% tallow had elevated serotonin in
      the raphe area compared with those fed 34% corn oil. In a third experiment, rats
      were fed either 34% corn oil or tallow for 2 days and then given dl-fenfluramine
      before diet selection. Fenfluramine depressed food intake to a greater degree in
      rats fed 34% tallow compared with those fed corn oil. These findings suggest that
      the diet selection behavior observed in tallow-fed rats may be mediated by a
      central serotonin system.

PMID- 1384353
TI  - Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation
      hypothesis.
AB  - During the progression of Mg deficiency in a rodent model, we have observed
      dramatic increases in serum levels of inflammatory cytokines [interleukin-1 (IL
      1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] after 3 wk
      on a Mg-deficient diet. Sequential analyses of these cytokine changes in the
      serum of rats revealed an initial rise at day 12, followed by a major elevation
      in all three cytokine levels by day 21. Of greater interest was an early peak in
      the serum level of the neuropeptide substance P after only 5 days on the diet.
      This "neuronal" tachykinin is thought to be released from neural tissues, and it
      is known to stimulate production of certain cytokines, including IL-1, IL-6, and
      TNF-alpha. In addition, there was a concomitant increase in histamine levels,
      which may have resulted from stimulation and degranulation of mast cells by
      substance P. Thus we hypothesize that the release of substance P may be the
      earliest pathophysiological event leading to stimulation of the inflammatory
      cytokines, which may then stimulate the free radical mechanisms of injury
      previously confirmed by our work.

PMID- 1384354
TI  - Substance P induces whole cell current transients in RBL-2H3 cells.
AB  - To investigate the basis of interactions between nerves and mast cells, we tested
      the actions of the neuropeptide substance P (SP) on whole cell current
      characteristics of RBL-2H3 cells (homologous to mucosal mast cells). Control RBL
      cells showed a K(+)-dependent inwardly rectified current. SP (10(-6) M) caused
      transient, frequently repetitive increases in current amplitude, which at a
      membrane potential (Vm) of -80 mV rose by -1,020.0 +/- 223.4 pA after SP
      application compared with -6.8 +/- 1.7 pA for control. This response was
      characterized by a lag phase of 102 +/- 16 s. Seventeen percent of cells showed
      spontaneous transients in the current amplitude from the beginning of the
      recording. After SP administration, the amplitude of these transients increased
      by 6.3 +/- 2.0-fold. Responses to SP were mimicked by the application of
      ionomycin. For both SP and ionomycin, there was a dose dependency of the lag
      phase. Removal of extracellular calcium abolished the response for 10(-6) M SP
      but not for 6.6 x 10(-6) M ionomycin. During current transients, the whole cell
      current had both inward and outward rectified components with the zero current Vm
      shifted from -87.3 +/- 3.2 mV at control to -10.8 +/- 1.7 mV. We compare the SP
      evoked current responses in mucosal-type mast cells with those described in
      connective tissue type.

PMID- 1384355
TI  - Detection of angiotensin I and II in cultured rat cardiac myocytes and
      fibroblasts.
AB  - Angiotensin II (ANG II) is a stimulus for positive chronotropic and inotropic
      effects, protein synthesis, and hypertrophic growth in cardiac tissue. These
      short- and long-term effects of ANG II are mediated through specific plasma
      membrane receptors. Indirect evidence suggests that ANG II synthesized in the
      myocardium may be important in regulating cardiac function. The cell types in the
      myocardium that produce components of the renin-angiotensin system have not been
      determined. In this study, we evaluated whether cultured cardiomyocytes and
      fibroblasts obtained from ventricles of neonatal rat hearts were capable of
      synthesizing ANG I and II. Both cardiomyocytes and fibroblasts were found to have
      immunofluorescent staining for ANG I, ANG II, and angiotensin-converting enzyme
      (ACE). The amounts of ANG I and II in cell extracts and conditioned media
      obtained from cardiomyocytes and fibroblasts were quantified by radioimmunoassay.
      The amounts of ANG I and II detected in cardiomyocyte cultures (1.48 x 10(6)
      cells/dish) were 32.2 +/- 16.2 (n = 4) and 6.2 +/- 2.9 (n = 4) ng/10(6) cells,
      respectively. The amounts of ANG I and II detected in the media conditioned by a
      48-h exposure to cardiomyocytes were 5.2 +/- 1.2 (n = 3) and 2.1 +/- 1.2 (n = 3)
      ng/10(6) cells, respectively. The amounts of ANG I and II detected in fibroblast
      cultures (5.38 x 10(6) cells/dish) were 34.8 +/- 4.9 (n = 4) and 8.0 +/- 3.5 (n =
      4) ng/10(6) cells, respectively. The amounts of ANG I and II obtained from media
      conditioned by a 48-h exposure to fibroblasts were 4.7 +/- 0.6 (n = 4) and 3.3 +/
      2.1 (n = 4) ng/10(6) cells, respectively. The identity of the
      radioimmunoassayable materials as ANG I and II peptides was confirmed in
      cardiomyocytes using an in vitro bioassay based on displacement of 125I-ANG II
      from receptor binding sites in cardiac membranes prepared from neonatal pig
      heart. Identification of ANG I and II and ACE in vitro in cultures of cardiac
      myocytes and fibroblasts supports the hypothesis that there is an intracardiac
      renin-angiotensin system that produces these peptides.

PMID- 1384356
TI  - Glucocorticoid increases glucose cycling and inhibits insulin release in
      pancreatic islets of ob/ob mice.
AB  - Normoglycemic ob/ob mice were treated for 24 or 48 h with either 25
      micrograms/day of dexamethasone or saline. After an overnight fast, the animals
      were killed and pancreatic islets were incubated with 3H2O or [U-14C]glucose or
      [5-3H]glucose at 5.5 and 16.7 mM glucose. Incorporation of 3H from 3H2O into
      carbon 2 of medium glucose and the yield of 14CO2 from [U-14C]glucose and 3H2O
      from [5-3H]glucose were measured. Dexamethasone treatment for 48 h significantly
      increased the rate of dephosphorylation of glucose in islets both at 5.5 mM (24
      vs. 16%) and 16.7 mM (56 vs. 36%) glucose, whereas glucose oxidation and
      utilization were unaffected. Dexamethasone treatment also inhibited insulin
      release by approximately 60% at 5.5 and 16.7 mM glucose, either in the presence
      or absence of 10 mM arginine, but had no effect when insulin release was
      stimulated by 1 mM 3-isobutyl-1-methylxanthine. Moreover, 24-h treatment with
      dexamethasone significantly increased glucose cycling at low and high glucose
      concentrations in the medium and inhibited insulin responsiveness to glucose and
      arginine. In conclusion, short-term dexamethasone treatment increases glucose
      flux through glucose-6-phosphatase in islets from ob/ob mice. This effect may
      contribute to the decreased insulin response to glucose and arginine found in
      animals treated with dexamethasone.

PMID- 1384357
TI  - Gastrin induction of histamine release from primary cultures of canine oxyntic
      mucosal cells.
AB  - Using enzyme-dispersed canine oxyntic mucosal cells, we studied regulation of
      histamine release from fractions in which mast cells were largely removed by
      density gradient. Histamine-like immunoreactivity was demonstrated using
      peroxidase-anti-peroxidase immunohistochemistry. Histamine-containing cells in
      the small cell elutriator fractions (SCEF) were further separated by albumin step
      density gradients. Approximately 2.5% of cells in the low density fraction (LDF)
      contained histamine-like immunoreactivity; this fraction was largely depleted of
      the more dense mast cells (0.5%). These two fractions were cultured for 48-64 h
      on a Matrigel substrate. The cell content of histamine and release into the
      medium were measured by radioenzymatic assay. Gastrin, carbachol, and forskolin
      increased histamine release from the LDF. The induction of histamine release by
      gastrin was evident within 5 min and was sustained for at least 60 min. The
      response to gastrin was dose dependent between concentrations of 10(-11) and 10(
      8) M. In contrast, in the mast cell-enriched SCEF, basal release was higher and
      gastrin was without effect; however, concanavalin A stimulated and epinephrine
      inhibited histamine release indicating that histamine-release mechanisms were
      intact in this fraction. Our methods provide a preparation of low density oxyntic
      mucosal histamine cells that demonstrate gastrin-responsive histamine release; we
      speculate that enterochromaffin-like cells account for this gastrin response.

PMID- 1384358
TI  - Galanin-induced alteration of electrolyte transport in the rat intestine.
AB  - Effects of rat and porcine galanin on rat intestinal ion transport were examined
      in vitro. In the rat distal colon, a sustained increase in short-circuit current
      (Isc) was produced by the serosal addition of rat galanin at a concentration as
      low as 10(-9) M, and a maximal increment was observed at 10(-7) M. Porcine
      galanin was approximately 100 times less potent than rat galanin. In the rat
      jejunum, rat galanin produced only a slight and transient decrease in basal Isc.
      The response to rat galanin was not influenced by atropine, hexamethonium, or
      amiloride, but was virtually abolished by tetrodotoxin or furosemide. Rat galanin
      did not significantly influence the increase in Isc elicited by electrical field
      stimulation in the rat colon and jejunum. Transmural unidirectional 22Na and 36Cl
      fluxes in the rat colonic mucosa were measured under short-circuited conditions,
      and rat galanin significantly decreased net sodium and net chloride absorption.
      These findings suggest that galanin acts as a secretory modulator in the rat
      colon via noncholinergic neural transmission.

PMID- 1384359
TI  - Toxicity of tubule fluid iron in the nephrotic syndrome.
AB  - This study was carried out in rats with nephrotoxic serum nephritis after
      autologous phase proteinuria was well established to determine the effect of
      tubule fluid iron chelation on the course of this disease. Deferoxamine
      administration caused a reduction in urinary iron potentially capable of
      catalyzing hydroxyl radical (.OH) formation and kidney iron uptake (224 +/- 60
      vs. 398 +/- 152 mg/kg). This was associated with a decrease rate of progression
      of renal failure over the 21-day study period (creatinine clearance -0. 199 +/-
      0.152 vs. -0.509 +/- 0.336 ml/min, P < 0.05) and improved survival (8/8 vs. 4/8,
      P < 0.05). In addition deferoxamine caused a reduction in urinary transferrin
      excretion (32 +/- 15 vs. 74 +/- 16 mg/day) and fractional excretion of
      transferrin (2.01 +/- 1 vs. 5.9 +/- 3.7%) and an increase in serum transferrin
      levels (229 +/- 36 vs. 139 +/- 45 mg/dl, all P < 0.05). It is suggested that iron
      presented to the tubule fluid as a result of the glomerular leak for transferrin
      is dissociated from transferrin. In turn the iron is available in a form capable
      of catalyzing .OH formation, resulting in lipid peroxidation of tubule cell
      membranes. Deferoxamine chelation of tubule fluid iron retards the development of
      both tubulointerstitial injury and superimposed glomerular sclerosis in this
      model of membranous nephropathy.

PMID- 1384360
TI  - L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion
      at physiological shear rates in vivo.
AB  - In vivo interactions between neutrophils and endothelial cells (EC) follow a
      multistep process involving two distinct neutrophil adhesion receptors. L
      selectin, constitutively functional on resting neutrophils, mediates an
      activation-independent primary interaction resulting in rolling along the venular
      wall. Subsequent activation of rolling neutrophils induces upregulation and
      functional activation of beta 2-integrins (CD11/CD18) leading to firm attachment.
      Based on previous findings we hypothesized that, under shear force, rolling may
      be essential for successful neutrophil-EC recognition. Here we report results of
      our studies of human neutrophil behavior in interleukin (IL)-1-activated rabbit
      mesentery venules, an interaction that requires both L-selectin and beta 2
      integrins. Rolling of human neutrophils is L-selection mediated; it was strongly
      reduced by monoclonal antibody inhibition or enzymatic removal of L-selectin.
      Furthermore, activation induced L-selectin shedding and, in a dose- and time
      dependent fashion, rendered neutrophils unable to recognize inflamed EC despite
      expression of active beta 2-integrins, which promoted adhesion in vitro.
      Neutrophils activated for 5 min or longer lost most of their ability to roll.
      However, 1-3 min after activation, rolling was reduced (not abolished), and cells
      that were still able to roll displayed a significant tendency for a CD18
      dependent transition from rolling to sticking. The whole sequence of events,
      rolling, sticking, and transendothelial migration, could be observed if an
      extravascular chemotactic stimulus was applied by superfusing mesenteries with
      leukotriene B4. Under such conditions, sticking and emigration was blocked when
      rolling was inhibited by enzymatic removal of L-selectin. Our results indicate
      that primary neutrophil interaction with inflamed EC through the L-selectin is a
      prerequisite for neutrophil function at physiological shear rates in vivo.

PMID- 1384361
TI  - Mechanism of enhanced myogenic response in arterioles during sympathetic nerve
      stimulation.
AB  - In a previous study we found that the arteriolar myogenic response was enhanced
      during sympathetic nerve stimulation in the cat sartorius muscle. In this study
      we determined whether the enhancement was unique to sympathetic nerve
      stimulation. Changes of arteriolar diameter and red cell velocity during femoral
      arterial pressure reduction from 110 to 60 mmHg were examined. Arterioles of 40
      microns diameter were constricted by norepinephrine infusion to a similar degree
      as sympathetic nerve stimulation. Arteriolar dilation to pressure reduction was
      significantly enhanced during norepinephrine infusion and was not significantly
      different from that during sympathetic nerve stimulation. This indicates that
      junctional release of transmitters is not essential and rules out prejunctional
      inhibition of neurotransmitter release during pressure reduction as a significant
      mechanism in the enhanced dilation. Arteriolar dilation to pressure reduction was
      also enhanced during vasopressin or BAY K 8644 (a calcium channel agonist)
      infusion. In all instances, autoregulation of flow was significantly enhanced.
      These results demonstrate that modulation of the myogenic response occurs at
      postreceptor sites in the smooth muscle cell.

PMID- 1384362
TI  - Recovery of anoxic-reoxygenated cardiomyocytes from severe Ca2+ overload.
AB  - The ability of hypoxic-reoxygenated cardiomyocytes to recover from severe
      cytosolic Ca2+ overload was investigated using the fluorescent Ca2+ indicator
      fura-2 in ventricular cardiomyocytes from adult rats. When the fura-2 ratio
      (340/380 nm) reached saturation in hypoxic cardiomyocytes, indicating severe Ca2+
      overload, they were reoxygenated. The cell then suddenly hypercontracted but
      reestablished, after a phase of Ca2+ oscillations, a normal Ca2+ control. Because
      these oscillations could be abolished by ryanodine (50 nM), they seem to depend
      on the function of the sarcoplasmic reticulum (SR). In the presence of caffeine
      (5 mM) and thapsigargin (100 nM), i.e., agents impairing Ca2+ sequestration in
      the SR, reoxygenation did not lead to Ca2+ oscillations or to a stable recovery
      of cytosolic Ca2+ control. The additional presence of ruthenium red (5 microM),
      an inhibitor of mitochondrial Ca2+ uptake, restored the ability of cells treated
      with caffeine or thapsigargin to reestablish a normal cytosolic Ca2+ control. The
      results show that cardiomyocytes are able to recover from severe hypoxic Ca2+
      overload if, first, a closed sarcolemma is retained (as in isolated
      cardiomyocytes) and, second, the SR is available for rapid Ca2+ storage (impaired
      by caffeine and thapsigargin). The results also suggest that, in the case of an
      impairment of SR function, the inhibition of mitochondrial Ca2+ uptake (as by
      ruthenium red) has a protective effect.

PMID- 1384363
TI  - Presence of C-type natriuretic peptide in cultured human endothelial cells and
      plasma.
AB  - The present study was undertaken to investigate the presence of C-type
      natriuretic peptide (CNP) immunoreactivity in cultured human vascular endothelial
      cells and in human plasma. CNP immunoreactivity was present in cultured human
      aortic endothelial cells by both immunohistochemical staining and by
      radioimmunoassay. With the utilization of gel permeation chromatography, this
      immunoreactivity proved to be consistent with the higher molecular weight CNP-53.
      CNP immunoreactivity was also present in human plasma (n = 22) at low picogram
      concentrations (6.5 +/- 0.2 pg/ml) by specific radioimmunoassay. This
      immunoreactivity was consistent with the lower molecular weight CNP-22 by gel
      permeation chromatography. These findings suggest that the vascular endothelium
      may be the site of CNP production. The isolation of different molecular forms of
      CNP in tissue and plasma may be consistent with a storage form of the peptide in
      endothelial cells CNP-53, while CNP-22 circulates in plasma. In summary, the
      present study is consistent with CNP being a peptide of endothelial cell origin.

PMID- 1384364
TI  - Technique for training schizophrenic patients in illness self-management: a
      controlled trial.
AB  - OBJECTIVE: To determine whether schizophrenic outpatients receiving low-dose
      neuroleptic therapy could learn and retain complex information and skills related
      to self-management of their illness, a novel technique of teaching, using
      cognitive and behavioral methods, was designed to compensate for the patients'
      learning disabilities. METHOD: The subjects were 41 patients with DSM-III-R
      schizophrenia who were receiving constant maintenance neuroleptic drug therapy.
      They were randomly assigned to structured, modularized skills training or to
      supportive group psychotherapy. RESULTS: The patients who received skills
      training made significant gains in each of the areas taught, while those
      participating in group therapy did not. The skills learned during training were
      retained without significant erosion over a 1-year follow-up period. CONCLUSIONS:
      The effectiveness of modularized teaching of illness self-management skills to
      schizophrenic patients appears to be largely independent of baseline psychology
      and symptom improvement. Such an approach is useful for overcoming or
      compensating for the enduring cognitive and information processing deficits
      commonly found in schizophrenia.

PMID- 1384365
TI  - The interchange of disease and health between the Old and New Worlds.
AB  - A review of the five centuries since Columbus discovered America helps us
      understand the mutual contributions of the Old and the New Worlds to the history
      of diseases and their treatment. It also shows the consequences of this "mutual
      discovery" as they are currently emerging in the fields of health, culture, and
      the environment. To evaluate the multiple aspects of the interchange between the
      Old and New Worlds, this paper discusses the following: the causes of the rapid
      decline of the original American populations; the diffusion of communicable
      diseases between the two civilizations; the health consequences of nutritional
      changes on both sides of the Atlantic; drug addictions, as they developed through
      the centuries and as they exist today; the ways diseases were and are evaluated,
      prevented, diagnosed, and treated; and the mutual impact of different models of
      health services. Arguing that a major global change following the discovery of
      America was the transition from isolation of the two worlds to communication,
      and, more recently, to global interdependence, the paper also discusses some
      problems of bioethical relevance and the possible impact of new epidemics.
      Finally, it suggests that a critical analysis of the past may help stimulate
      future cooperation and solidarity.

PMID- 1384366
TI  - Metastatic prostatic carcinoma presenting as an oncocytic tumor.
AB  - We discuss a 63-year-old man who presented with a metastatic tumor in an inguinal
      lymph node. By light microscopy, the tumor cells were characterized by a finely
      granular eosinophilic cytoplasm. A diagnosis of metastatic oncocytic carcinoma
      was made based on the results of an ultrastructural examination, which showed the
      cytoplasm of the tumor cells to be filled with mitochondria. Results of
      immunocytochemical studies showed positive reactivity for prostatic acid
      phosphatase and prostate-specific antigen. A transurethral resection of the
      prostate showed an oncocytic adenocarcinoma of the prostate, apparently the first
      of its kind, which was demonstrated to be the site of origin of the inguinal
      lymph node metastasis.

PMID- 1384367
TI  - Intraarticular synovial sarcoma.
AB  - A 43-year-old man presented with decreased range of motion in his left knee and a
      painful medial joint mass that was grossly visible. Arthroscopy demonstrated a
      mobile, flat mass 3 cm in diameter in the knee joint that seemed to be loosely
      tethered to the synovium. The mass was excised, and light microscopic examination
      demonstrated a biphasic synovial sarcoma. There was no transition with the
      attached normal synovium. Immunohistochemically, the epithelial component was
      intensely positive for epithelial membrane antigen and cytokeratins (CAM 5.2 and
      AE 1/AE 3), and the spindle cell component was focally positive for these
      markers. The patient has no evidence of disease 9 years after only local
      excision. Although the term synovial sarcoma suggests a relationship to normal
      synovium, only rarely has truly intraarticular disease been reported.

PMID- 1384368
TI  - Primary ovarian small cell carcinoma of pulmonary type. A clinicopathologic,
      immunohistologic, and flow cytometric analysis of 11 cases.
AB  - Eleven primary ovarian tumors that resembled small cell carcinoma of the lung are
      reported. They occurred in women 28-85 (mean 59) years of age, most of whom
      presented with abdominal swelling. Six of the tumors were unilateral and five
      bilateral; seven had spread beyond the ovary. The tumors ranged from 4.5 to 26
      (mean 13.5) cm in greatest dimension and were mostly solid, with a variable minor
      cystic component. Microscopic examination showed small to medium-sized round to
      spindle-shaped cells with scanty cytoplasm, hyperchromatic nuclei, and
      inconspicuous nucleoli growing in sheets, closely packed nests, and occasionally
      islands and trabeculae. A component of endometrioid carcinoma was present in four
      tumors, another tumor showed squamous differentiation, another contained a cyst
      lined by atypical mucinous cells, and two others were associated with a Brenner
      tumor. Argyrophil granules were present focally in two of six tumors
      appropriately stained. Immunohistochemical staining was performed in nine cases:
      in six there was staining of the small cell component for keratin, in five for
      epithelial membrane antigen, in seven for neuron-specific enolase, in two for
      chromogranin, and in one for Leu-7. Vimentin staining was not observed. Flow
      cytometry was performed on eight tumors: five were aneuploid and three diploid.
      Five of seven patients with long-term follow-up died of, or with, disease at 1-13
      (mean 8) months, one died after an unknown interval, and one was alive at 7.5
      years. Two other patients had recurrent or residual disease at 6 and 8 months.

PMID- 1384369
TI  - Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and
      immunohistochemical study of 40 cases.
AB  - In this study of 40 cases of basaloid squamous cell carcinoma, 83% arose in the
      pyriform sinus, base of tongue, tonsil, and larynx. The 35 men and five women
      ranged in age from 27 to 88 years (median 62). In patients for whom social habits
      were recorded, 24 of 26 patients were smokers and 22 of 25 drank ethanol. Most
      presented with stage III or IV disease. Twenty-seven patients had regional
      metastases at the time of presentation and 15 developed distant metastases.
      Seventeen patients died with disease (median survival 18 months). The tumors were
      composed of moderately pleomorphic basaloid cells forming nests, cords, and
      frequent cribriform patterns. Squamous dysplasia of surface mucosa, focal
      squamous differentiation within invasive basaloid squamous cell carcinoma, or
      foci of conventional squamous cell carcinoma were present, alone or in
      combination. All studied neoplasms were immunohistochemically positive for
      keratins with the 34 beta E12 antibody. Approximately 80% were immunoreactive
      using AE1/AE3 or CAM 5.2. Epithelial membrane antigen, carcinoembryonic antigen,
      and S100 protein were found in 83%, 53%, and 39%, respectively, of the cases.
      Diffuse, weak immunoreactivity for neuron-specific enolase was seen in 75% of
      tumors. Synaptophysin, chromogranin, muscle-specific actin, and glial fibrillary
      acidic protein were absent. Basaloid squamous cell carcinoma has been confused
      with adenoid cystic carcinoma and small cell undifferentiated carcinoma, but is
      usually distinguishable in routine hematoxylin and eosin-stained sections, or, in
      rare problematic cases, with the aid of immunohistochemical studies. Distinction
      is warranted because the biologic behavior of basaloid squamous cell carcinoma
      differs from that of both of these lesions.

PMID- 1384370
TI  - Intermediate filamentous proteins in adult granulosa cell tumors. An
      immunohistochemical study of 25 cases.
AB  - Adult granulosa cell tumors (AGCTs) are classified as sex cord-stromal tumors of
      the ovary. However, they may be confused with other primary ovarian neoplasms.
      Intermediate filaments, specifically vimentin and cytokeratins, have been
      identified in AGCTs by immunohistochemistry performed on frozen and formalin
      fixed, paraffin-embedded tissue and two-dimensional electrophoresis. Recently,
      however, immunohistochemical demonstration of cytokeratin has been used as
      supporting evidence of epithelial rather than sex cord-stromal differentiation in
      ovarian neoplasia. To investigate further intermediate filamentous proteins in
      AGCTs, 25 such tumors were studied by immunohistochemistry in formalin-fixed,
      paraffin-embedded sections. Cytoplasmic staining was observed, frequently in a
      distinct punctate, paranuclear pattern, in 14 of 25, 14 of 25, and seven of 17
      tumors using monoclonal antibodies AE1/AE3, CAM 5.2, and 35BH11, respectively,
      which share the ability to detect low molecular weight cytokeratins. Staining for
      cytokeratin was not seen in any of the 17 tumors studied using the antibody
      34BE12. Twenty-three of 25 tumors showed strong positivity for vimentin,
      characteristically seen as globoid paranuclear staining. Nine of 25 tumors
      contained desmin, which was restricted to the intermixed spindle cell, cortical
      type stromal component of the tumors. These patterns of immunoreactivity for
      intermediate filaments, particularly cytokeratins, are different than in common
      epithelial tumors of the ovary and may be useful in the differential diagnosis of
      ovarian neoplasia. Moreover, the immunohistochemical detection of cytokeratins
      should not be used as a criterion for excluding AGCT from the differential
      diagnosis of an ovarian neoplasm.

PMID- 1384371
TI  - Malignant pleural mesothelioma producing human chorionic gonadotropin. Report of
      two cases.
AB  - Two cases of malignant pleural tumor producing human chorionic gonadotropin, one
      confirmed at surgery and autopsy and the other by biopsy, are reported. Both of
      the patients had bilateral gynecomastia with high levels of serum human chorionic
      gonadotropin. The first patient underwent panpleuropneumonectomy because of
      diffuse malignant pleural tumor, but died five months later due to recurrent
      disease. The histological diagnosis was diffuse, malignant, monophasic
      mesothelioma of the epithelial type. Immunostaining for alpha-, beta-human
      chorionic gonadotropin and human placental lactogen was positive in
      syncytiotrophoblast-like cells. The second patient had diffuse pleural tumor with
      massive effusion. A pleural biopsy specimen showed diffuse proliferation of
      epithelioid large cells. Immunostaining for alpha, beta-human chorionic
      gonadotropin and human placental lactogen was positive in mono- and
      multinucleated bizarre giant cells mimicking trophoblasts. A diagnosis of
      malignant mesothelioma with trophoblastic differentiation seemed most likely in
      both cases in view of the clinical and pathological findings. In both cases,
      results of mucin histochemistry and various immunohistochemical stains for
      antigens or with antibodies were consistent with diagnosis of mesothelioma except
      in a few cells in the choriocarcinomatous portion. This may be the first report
      describing human chorionic gonadotropin-producing malignant mesotheliomas of the
      pleura.

PMID- 1384372
TI  - Neoplastic epithelial cells in a subset of human thymomas express the B cell
      associated CD20 antigen.
AB  - A series of 36 human thymomas have been immunohistochemically analyzed using a
      panel of antibodies recognizing B-cell markers including CD20. Most thymomas
      exhibiting the cortical pattern, according to the criteria of Marino and Muller
      Hermelink, were characterized by areas of medullary differentiation containing
      variable numbers of CD20+ B lymphocytes, thus mimicking the medulla of normal
      thymus. On the other hand, B cells were absent or rare in thymomas recognized as
      mixed using the same morphological criteria. Surprisingly, we observed in most
      mixed thymomas variable numbers of CD20+ spindle cells, characterized by long
      slender processes. Using double-marker analysis we could demonstrate the
      epithelial nature of these cells (expression of keratin and lack of lymphoid and
      B-cell-related markers). The immunoreactivity of thymoma epithelial cells with
      L26, an antibody widely used in the characterization of B-cell lymphomas, can
      represent a drawback of practical relevance in the differential diagnosis of
      mediastinal tumors.

PMID- 1384373
TI  - Desmoplastic primitive neuroectodermal tumor with divergent differentiation.
      Broadening the spectrum of desmoplastic infantile neuroepithelial tumors.
AB  - We report an unusual large, multicystic, posterior fossa neuroepithelial neoplasm
      involving the cerebellum, brain-stem, and quadrigeminal cistern of a 9-month-old
      girl. The neoplasm consisted of variably sized, sharply demarcated nests of small
      cells with a high nuclear-cytoplasmic ratio and moderately basophilic nuclei,
      embedded in a desmoplastic, immature-appearing, mesenchymal stroma. The nests
      contained mitoses but none were seen in the stroma. Glial fibrillary acidic
      protein (GFAP), neurofilament protein, synaptophysin, and cytokeratin (AE-1) were
      expressed in the nests. Mesenchymal cells were negative for neural markers but
      positive for vimentin and desmin. The neoplasm was interpreted as a mixed
      mesenchymal and primitive neuroectodermal tumor (PNET) with histologic features
      reminiscent of a recently described intraabdominal desmoplastic small cell tumor.
      The tumor responded poorly to chemotherapy and a second operation was performed 1
      year later. The second specimen bore no resemblance to the original and consisted
      of epithelial-like nests and clusters of neoplastic cells frequently interrupted
      by sinusoidal vessels. Tumor cells had medium-sized vesicular nuclei with small
      nucleoli, and a granular cytoplasm. Occasional less cellular islands of neuropil
      like tissue contained larger cells having eccentric, vesicular nuclei with
      prominent nucleoli and abundant pink cytoplasm. Mitoses were not conspicuous.
      Many cells expressed synaptophysin, neurofilament protein, and GFAP.
      Neurofilament protein was strongly positive in the larger, neuron-like cells and
      synaptophysin stained the neuropil-like areas strongly but was less prominent in
      the neuronal perikarya. Unexpectedly, the neuropil-like areas expressed
      epithelial membrane antigen, whereas the neuronal cells were negative for
      chromogranin A. The peculiar histologic picture, combination of phenotypic
      markers, and remarkable biologic behavior of this unusual tumor defies
      classification according to existing nomenclature and exemplifies the broad range
      of phenotypes expressed by primitive neuro-epithelial neoplasms.

PMID- 1384374
TI  - Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases.
AB  - We have examined the microscopic appearance, immunohistochemical staining
      properties, and clinical behavior of 28 cases of acinar cell carcinoma of the
      pancreas. Two of the tumors occurred in children. The adult patients ranged in
      age from 40 to 81 years (mean, 62 years). Males greatly outnumbered females, and
      most of the patients were white. Presenting symptoms were nonspecific, and
      jaundice was infrequent. The frequently reported complications from increased
      serum lipase levels (i.e., arthralgias and subcutaneous fat necrosis) were
      present in only 16% of the patients. Grossly, the tumors were relatively
      circumscribed and fleshy, averaging 10.8 cm, with occasionally extensive
      hemorrhage and necrosis. Microscopically, the tumors were very cellular and
      characteristically lacked a desmoplastic stroma. Acinar, solid, trabecular, and
      glandular patterns of growth were identified; individual tumors were usually
      mixed. Nuclei were round to oval, with minimal pleomorphism and single prominent
      nucleoli. Mitotic activity was variable. In general the cytoplasm was moderately
      abundant, eosinophilic, and granular, but many of the solid tumors had cells with
      scanty cytoplasm. Characteristic periodic acid-Schiff-positive, diastase
      resistant cytoplasmic granules were demonstrated in greater than 90% of the
      cases, and the butyrate esterase histochemical stain for lipase activity was
      positive in 73%. Immunohistochemically, there was positivity for trypsin in 100%
      of the cases, for lipase in 77%, for chymotrypsin in 38%, and for amylase in 31%.
      A minor endocrine component was recognized with antibodies against chromogranin
      or islet cell hormones in 42% of the tumors. Ultrastructurally, exocrine
      secretory features were present, with polarized cells showing microvillilined
      lumina, abundant rough endoplasmic reticulum, and 125-1,000-nm zymogen-like
      granules. In addition, many cases showed pleomorphic electron-dense granules
      measuring up to 3,500 nm and containing fibrillary internal structures. Follow-up
      information was available in 88% of the cases. Half of the patients had
      metastatic disease at presentation and an additional 23% subsequently developed
      metastases, which were usually restricted to the regional lymph nodes and liver.
      The mean survival for all cases was 18 months, with 1- and 3-year survivals of 57
      and 26%, respectively. Patients presenting before age 60 years survived nearly
      twice as long as older patients did. Stage also influenced prognosis, whereas the
      histologic subtype of the tumors and the location within the pancreas correlated
      only weakly with survival.

PMID- 1384375
TI  - Metastasizing mixed tumor of salivary glands. A clinicopathologic and flow
      cytometric analysis.
AB  - Among salivary gland neoplasms are a group of rare tumors that are histologically
      identical to benign mixed tumors that inexplicably metastasize; they have been
      called metastasizing mixed tumor (MZMT) of salivary glands. We report the
      clinicopathologic features and flow cytometric findings for 11 cases of MZMT. At
      the time of discovery of metastatic disease, the patients, six women and five
      men, ranged in age from 20 to 83 years. Primary sites of involvement included the
      parotid gland (eight cases), submandibular gland (two cases), and the nasal
      septum (one case). With one exception, all the patients had at least a single
      recurrences of their primary mixed tumor, but two or more recurrences were the
      norm before development of metastatic foci. The metastases were discovered from
      six to 52 years following the occurrence of the primary tumor. Metastatic
      deposits were identified in bone, lung, regional lymph nodes, skin, kidney,
      retroperitoneum, oral cavity, pharynx, calvarium, and central nervous system. The
      metastases either occurred simultaneously with an episode of recurrent mixed
      tumor (n = 5) or from 5 to 29 years after a recurrence (n = 6). The treatment of
      the primary, recurrent, and metastatic neoplasms was surgical excision. Follow
      up, ranging from 8 months to 16 years following the diagnosis of MZMT, revealed
      seven patients to be alive without disease (64%) and two dead of causes unrelated
      to metastatic disease (18%). Two patients (18%) died as a direct result of
      metastatic tumor at 3 and 2 years after metastasis of their mixed tumors. Flow
      cytometric analysis revealed a diploid DNA cell population in the primary and/or
      metastatic tumors in nine cases. Aneuploid DNA cell content was identified in two
      of the cases. DNA ploidy levels and cell proliferation rates were compared with
      those of conventional benign mixed tumors and also with malignant mixed tumors.
      Retrospective analysis of histologic parameters (mitotic rate, cellular
      pleomorphism, infiltrative growth, vascular or lymphatic invasion) and flow
      cytometric analysis failed to identify criteria to predict the development of
      metastasis in these neoplasms.

PMID- 1384377
TI  - Adenomyoepithelioma of the breast. A spectrum of biologic behavior.
AB  - Adenomyoepitheliomas of the breast have been considered to have limited
      metastatic potential; axillary node metastasis has been reported, but there has
      been no report of distant metastasis. We report six cases, including two
      malignant adenomyoepitheliomas, one of which metastasized to the lung and brain.
      Patient age ranged from 26 to 63 years (mean 46). Primary tumors were solitary
      and measured 0.9-3.5 cm (mean 1.7). Five of six tumors presented as palpable
      masses. Two patients treated by local resection have no evidence of disease at 5
      and 18 months' follow-up. Two patients treated by local resection had
      recurrences, one at 48 the other at 60 months. The fifth patient had a spindle
      cell type adenomyoepithelioma diagnosed as malignant because of high mitotic rate
      and cytologic atypicality of the myoepithelial component. This patient was
      treated by mastectomy and has no evidence of disease at 18 months. The sixth
      patient, initially treated by local excision, had six local recurrences over 52
      months treated by reexcisions, mastectomies, and radiation. A lung metastasis was
      resected at 54 months and brain metastases were identified at 60 months with
      death occurring at 64 months. Both malignant adenomyoepitheliomas had high
      mitotic rates [11-14/10 high-power fields (HPF)] diffusely throughout the tumors
      and foci of cytologically malignant cells. The malignant adenomyoepithelioma that
      metastasized had an infiltrative growth pattern that increased with successive
      local recurrences. The four other tumors had only isolated areas of mitotic
      activity (maximum 1-9/10 HPF) and minimal cytologic atypia. Immunohistochemistry
      performed on five of six cases confirmed dual epithelial/myoepithelial cell
      populations in all tumors examined, including the metastasis. Electron
      microscopic examination of the malignant adenomyoepithelioma that metastasized
      also confirmed dual epithelial/myoepithelial cell populations in a local
      recurrence and the lung metastasis. We conclude that there is a spectrum of
      behavior for breast adenomyoepitheliomas with potential for local recurrence and,
      rarely, distant metastasis.

PMID- 1384376
TI  - Chronic lymphocytic leukemia/small lymphocytic lymphoma with Reed-Sternberg-like
      cells and possible transformation to Hodgkin's disease. Mediation by Epstein-Barr
      virus.
AB  - The pathogenesis of Reed-Sternberg cells and variants (RS-H cells) found in rare
      cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is
      unknown. We studied 13 such cases by immunohistochemistry and in situ
      hybridization for identification of Epstein-Barr virus (EBV) RNA. The RS-H cells
      in five cases expressed the B-lineage marker CD20 and were negative for CD15. In
      two cases, the RS-H cells showed expression of both CD20 and CD15, whereas in
      another six cases, the cells were positive for CD15 but negative for CD20. Three
      of the cases expressing CD15 showed subsequent evidence of disseminated Hodgkin's
      disease. Regardless of the phenotype or clinical behavior, the RS-H cells in 12
      of 13 cases were found to contain EBV RNA by in situ hybridization, but the
      surrounding neoplastic lymphocytes were invariably negative for EBV RNA. It is
      suggested that EBV has an important role in the pathogenesis of the RS-H cells in
      these rare cases.

PMID- 1384378
TI  - Lymphoepitheliomalike carcinoma of the skin. A case report with immunophenotypic
      analysis and in situ hybridization for Epstein-Barr viral genome.
AB  - Lymphoepithelioma is a malignant epithelial neoplasm of the nasopharynx. Similar
      malignancies--lymphoepitheliomalike carcinomas--of salivary glands, thymus,
      larynx, lung, stomach, and uterus have been described. We present here a case of
      lymphoepitheliomalike carcinoma of the skin in an 84-year-old woman.
      Histologically this neoplasm presented as a fairly discrete dermal aggregate of
      syncytial nests of epithelioid-appearing cells that displayed no squamous or
      glandular differentiation, surrounded by a dense lymphocytic infiltrate. Results
      of immunophenotypic studies showed expression of high molecular weight
      cytokeratins and increased density of dermal dendrocytes within and adjacent to
      the tumor. No Epstein-Barr viral genomic sequences were detected by in situ
      hybridization, which suggests that cutaneous neoplasms may have different
      etiologic agents compared with similar tumors, found to be associated with this
      DNA-containing virus, arising in extracutaneous sites. The combined light
      microscopic and immunohistochemical assessment of this rate cutaneous neoplasm
      permits distinction of lymphoepitheliomalike carcinoma from benign/malignant
      lymphoproliferative disorders or neuroendocrine carcinomas.

PMID- 1384379
TI  - Malignant eccrine spiradenoma. A clinicopathologic study.
AB  - Malignant eccrine spiradenomas (MES) are exceedingly rare and their
      immunohistochemical and ultrastructural features have not been fully
      characterized. We studied two cases, one of them immunohistochemically and
      electron microscopically. Patient 1 had a 25-year history of multiple exophytic
      tumors involving the scalp, the skin of the face, and the torso. Of the lesions
      removed, ten were spiradenomas, two with malignant changes, and three were
      cylindromas. The malignant areas showed loss of tubular and nesting patterns,
      lack of two cell populations, and contained anaplastic cells with high mitotic
      rate. The immunohistochemical findings were consistent with eccrine
      differentiation. Patient 2 had a cystlike mass of long duration in the right
      groin. Histologically, the mass consisted of nodules of benign eccrine
      spiradenomas adjacent to a ductal-cystic mass lined by anaplastic cells, but
      areas of squamous and glandular differentiation were also present. CONCLUSIONS:
      (a) Case 1 is probably the first reported MES associated with multiple
      spiradenomas and cylindromas. (b) Cytodifferentiation in MES is variable,
      sometimes with almost complete loss of eccrine differentiation. (c)
      Identification of adjacent spiradenomas may be required for definite diagnosis of
      MES. (d) Clinical history of longstanding lesions with recent fast growth
      warrants tissue diagnosis.

PMID- 1384380
TI  - Immunohistochemical stains in extramammary Paget's disease.
AB  - The histologic and immunohistochemical characteristics of 49 skin biopsy
      specimens from 49 patients with extramammary Paget's disease were studied.
      Patients with extramammary Paget's disease with and without underlying malignant
      disease were identified. Associated malignant lesions, present in 16 patients
      (33%), were transitional cell carcinoma of the bladder (n = 8), adenocarcinoma
      underlying the skin (n = 3), adenocarcinoma of the anus (n = 1), adenocarcinoma
      of the vulva (n = 1), apocrine carcinoma (n = 1), prostate carcinoma (n = 1), and
      carcinoma metastatic to the lung (n = 1). The main histologic feature was the
      presence of Paget's cells, predominantly at the base of the epidermis. In 6% of
      the cases, well-defined nests of large Paget's cells mimicked melanocytic nests.
      Carcinoembryonic antigen and Cam 5.2 (a monoclonal antibody that stains 40-kDa,
      45-kDa, and 52.5-kDa low molecular weight keratins) were localized to the Paget's
      cells in 42 of 45 (93%) and 29 of 41 cases (71%), respectively. Forty-four of 46
      lesions (96%) were mucin positive, as determined by Hale's colloidal iron stain.
      Absence of staining for colloidal iron and carcinoembryonic antigen occurred
      somewhat more frequently in patients with underlying malignant disease than in
      patients without tumors (13% vs. 0% mucin negative and 13% vs. 3%
      carcinoembryonic antigen negative, respectively). Although immunohistochemical
      staining for low molecular weight keratin may be used to confirm the diagnosis of
      extramammary Paget's disease, Cam 5.2 is not as sensitive as the colloidal iron
      or carcinoembryonic antigen stain.

PMID- 1384381
TI  - Staining for enzymatic activity after gel electrophoresis. II. Enzymes modifying
      nucleic acids.

PMID- 1384382
TI  - Microplate reader-based quantitation of collagens.
AB  - By using a picrosirius dye, sensitive and specific staining of collagens plated
      in microtiter wells was achieved. The range of detection was from 0.5 to 20
      micrograms. Human collagen types I, III, IV, and V were tested and able to be
      detected by the method. The dye did not bind to acetylcholinesterase or elastin.
      It did bind to C1q to some extent but this is not surprising since the molecule
      contains some triple helical collagen-like structures. A comparison performed
      between this assay and a colorimetric assay for hydroxyproline using tissue
      culture supernatants gave similar results for both samples. Due to its simplicity
      and sensitivity this assay will be most useful in laboratories where large
      numbers of samples must be screened for collagen production.

PMID- 1384383
TI  - A spectrophotometric assay of Zn(2+)-glycerophosphorylcholine phosphocholine
      phosphodiesterase using p-nitrophenylphosphorylcholine.
AB  - A direct spectrophotometric assay for the glycerophosphorylcholine phosphocholine
      phosphodiesterase requiring zinc ions for activity is described. This assay is
      based on the continuous measurement of p-nitrophenol produced from the enzymatic
      hydrolysis of p-nitrophenylphosphorylcholine. The assay method, which showed a
      good linearity with time and amount of protein, was found to be rapid, simple,
      and, at the same time, accurate and sensitive enough to allow the quantitation of
      nanomolar amounts of product. With an alkaline buffer containing Triton X-100,
      the Zn(2+)-glycerophosphorylcholine phosphocholine phosphodiesterase activity in
      the tissue homogenate can be directly and selectively measured by this technique.
      The specific activity of the phosphodiesterase in brain and kidney was determined
      to be 80 and 6.5 nmol/h mg protein, respectively, and much lower activity was
      present in other tissues.

PMID- 1384384
TI  - Rapid analysis of mitotic histone H1 phosphorylation by cationic disc
      electrophoresis at neutral pH in minigels.
AB  - A new method is described for analysis of histone H1 and other basic proteins by
      cationic disc electrophoresis in polyacrylamide gels at neutral pH. The
      multiphasic buffer (disc) system uses Na+ as leading ion, L-histidine as trailing
      ion, and Hepes as buffering counterion. These "Hepes/histidine gels" have three
      advantages over conventional acid-urea gels for studies of H1 phosphorylation and
      dephosphorylation: speed, convenience, and the need for only small amounts of
      cells or chromatin. Core histones and their acetylated forms can also be
      separated in gels containing 0.4% Triton X-100. The difference in electrophoretic
      mobility between mitotic (superphosphorylated) and interphase H1 from HeLa cells
      is approximately twice as great at neutral pH as at pH 4.5, making it possible to
      separate these two H1 forms rapidly and easily in Hepes/histidine "minigels" only
      5-cm long. Total histones can be rapidly prepared by simply neutralizing 0.2 N
      HCl extracts, and the entire analysis, from harvesting cells to destaining gels,
      can be carried out in 1 day. The stacking effect of the disc system produces
      sharp bands and high resolution even with relatively dilute samples.

PMID- 1384386
TI  - A rapid and versatile method for cloning viroids or other circular plant
      pathogenic RNAs.
AB  - We surveyed the occurrence of unique restriction sites on the cDNAs of viroids,
      virusoids, and plant viral satellite RNAs that have a circular RNA as an
      intermediate of replication and found that four such sites would linearize their
      circular cDNAs. A rapid and simple method was then developed for cloning a
      naturally occurring viroid from Nematanthus wettsteinii plants. First-strand cDNA
      was synthesized using random hexanucleotide DNA primers and M-MuLV reverse
      transcriptase (Superscript RT). Second-strand DNA was synthesized by employing
      the replacement synthesis method using Escherichia coli RNase H, E. coli DNA
      polymerase I, E. coli DNA ligase, and beta-NAD+. The circular double-stranded DNA
      was analyzed for the presence of commonly available, unique restriction sites and
      subsequently linearized with a selected restriction enzyme. The linear cDNA was
      ligated to dephosphorylated plasmid vector pGEM 3Z f(+) and cloned in E. coli
      strain DH5 alpha. This cDNA cloning procedure is suitable for cloning sequence
      variants of well-characterized viroids, virusoids, certain plant viral satellite
      RNAs, and new such pathogens of unknown sequence.

PMID- 1384385
TI  - Incorporation of a bacterial membrane-bound hydrogenase into proteoliposomes.
AB  - Membrane-bound nickel-iron hydrogenases from diverse genera of bacteria have been
      previously characterized and they are closely related. We report the
      reconstitution of purified Bradyrhizobium japonicum hydrogenase into
      proteoliposomes by a detergent dialysis method followed by two or three cycles of
      freeze-thaw. Sedimentation experiments revealed that more than 60% of the H2
      uptake activity was particulate when reconstituted into Escherichia coli
      phospholipids. Sucrose-gradient centrifugation separated hydrogenase activity
      into two peaks, the less dense of which was phospholipid-associated and turbid,
      thereby showing successful incorporation. Purified enzyme did not bind to
      performed phospholipid vesicles, and 1.0 M NaCl failed to remove incorporated
      hydrogenase. The optimal micellar detergent:phospholipid ratio (rho) value for
      hydrogenase incorporation was 2.0. Proteoliposomes containing acidic
      phospholipids were the most effective for incorporation as well as for activity.
      The artificial electron acceptor specificity was similar for proteoliposomes and
      for H2-oxidizing membranes from B. japonicum. Proteoliposomes formed under
      optimal conditions had a broad size distribution centered around 400 nm diameter.
      Hydrogenase activity in proteoliposomes was partially protected from inactivation
      by the protein modification reagent diazobenzene sulfonate (DABS) (inactivation
      t1/2 = 30 min), whereas DABS rapidly inactivated the purified enzyme (t1/2 = 4
      min). The latter result indicates protection of a catalytically important site by
      the phospholipid bilayer. This experimental system should be useful in addressing
      questions regarding the in vivo situation of bacterial membrane-bound
      hydrogenases.

PMID- 1384388
TI  - RNA isolation from cartilage using density gradient centrifugation in cesium
      trifluoroacetate: an RNA preparation technique effective in the presence of high
      proteoglycan content.
AB  - An efficient method for the isolation of RNA from cartilage is described. The
      difficulties in obtaining RNA from cartilage, a tissue of low cell density and
      high proteoglycan content, were overcome by making several modifications to the
      guanidine thiocyanate/cesium chloride method of RNA extraction. Cartilage tissue
      is frozen, crushed, and homogenized in a 4 M guanidine thiocyanate lysis buffer.
      The RNA is then pelleted by ultracentrifugation through a cesium trifluoroacetate
      density gradient. The use of cesium trifluoroacetate, rather than cesium
      chloride, for density gradient centrifugation improves both the yield and purity
      of total RNA isolated from cartilage. The ultracentrifugation has been adapted to
      the Beckman TL100 tabletop centrifuge and is complete in 3 h. This fast, simple
      method produces high quality RNA, suitable for use in RNase protection assays,
      polymerase chain reaction analysis, and Northern analysis. This purification
      procedure may be applicable to other sources, from which RNA isolation is
      complicated by the presence of abundant cell wall or matrix components.

PMID- 1384387
TI  - A semiautomated, 96-well plate assay for collagen synthesis.
AB  - We have established a rapid method for the measurement of collagen synthesis in
      large numbers of cell cultures. 3H-labeled collagen in microwell cultures was
      salt precipitated, harvested, and washed using a commercially available cell
      harvester and the filtered collagen was directly counted. The cell number could
      then be assessed either by methylene blue staining or by dissolving the cells in
      NaOH and estimating the protein content with bicinchoninic acid. In all of these
      procedures, the samples remain in microtiter plates, thus ensuring that minimal
      amounts of reagents are used and minimizing the amount of manipulation necessary.
      The intergroup variability is 3 to 9% and the recovery of 3H-labeled collagen is
      greater than 90%. Using this method, large numbers of samples can be assessed for
      collagen synthesis quickly, conveniently, and for minimal cost.

PMID- 1384389
TI  - Centrifugal size-exclusion chromatographic method for rapid desalting and
      filtering of carbohydrate samples prior to fast atom bombardment mass
      spectrometry.

PMID- 1384390
TI  - Analysis of antibodies and other large glycoproteins in the mass range of 150,000
      200,000 Da by electrospray ionization mass spectrometry.
AB  - The analytical applicability of electrospray ionization mass spectrometry (ESIMS)
      to large glycoproteins in the molecular weight (MW) range of 150,000-200,000 was
      demonstrated. Multiply charged ions (charge state as high as 150+) of several
      typical macrosized glycoproteins of immunological significance were generated by
      pneumatically-assisted electrospray (ionspray) and their masses measured on a
      quadrupole mass spectrometer having a mass-to-charge (m/z) range of 2400. The
      resolution of the quadrupole instrument was insufficient to resolve the
      glycocomposition microheterogeneities in the MW range studied. Nevertheless, the
      average MWs of three immunoglobulin G (IgG) class murine monoclonal antibodies,
      anti-(human alpha 1-antitrypsin) (148,484 +/- 4), anti-(human alpha 1-acid
      glycoprotein) (149,599 +/- 12) and anti-(beta-galactosidase) (component I,
      150,544 +/- 10, and component II, 151,496 +/- 17), and human alpha 2
      macroglobulin monomer (186,100 +/- 100), and human complement component C4
      (196,863 +/- 29) were still determined from the fused peak profiles of their
      constituent glyco components (the errors given reflect the measurement precisions
      of the simultaneous multichannel MW determinations). The difference between the
      measured average MW and the unmodified sequence MW was used to assess the degree
      of post-transitional modification in human alpha 2-macroglobulin (13.6%) and
      human complement component C4 (5.3%). For the large glycoproteins studied here,
      glycosylation did not appear to seriously affect the effectiveness of the
      electrospray ionization; up to 70% of their full charge-retaining capacities were
      fulfilled under the usual experimental conditions. These results show that ESIMS
      is capable of providing analytically useful information for macrosized proteins.

PMID- 1384391
TI  - Trabecular generation de novo. A morphological and immunohistochemical study of
      primary ossification in the human femoral anlagen.
AB  - An understanding of trabecular formation in early skeletal development may
      provide insight into the problem of trabecular replacement in the aging skeleton.
      In an optical and scanning electron microscope study of the processes of de novo
      trabecular generation, the immunohistochemical distribution of collagen Types I,
      II and III, together with the matrix organising proteins fibronectin and
      tenascin, has been examined in the ossifying human femoral anlage. In the region
      of the developing spongiosa, the primary osseous trabeculae that arose by
      endochondral ossification were assembled around calcified cartilage remnants,
      consisting almost entirely of aggregates of mineralised microspheres. These
      structures were specifically recognised by antibodies raised against collagen
      Type II and fibronectin. In contrast, the primary osseous trabeculae that arose
      by subperiosteal intramembranous processes, were assembled around a framework of
      prominent coarse fibres that were recognised by antibodies raised against
      collagen Type III and tenascin. Irrespective of their origin, all the new
      trabeculae were similar in their general staining character for collagen Type I
      and fibronectin. However, throughout the developmental stages examined here
      endochondral trabeculae were separated from intramembranous trabeculae by a
      discrete boundary of compressed cells and mineralised cartilage.

PMID- 1384392
TI  - The effects of growth factors on the day 13 chorioallantoic membrane (CAM): a
      study of VEGF165 and PDGF-BB.
AB  - The in vivo effects of two growth factors, VEGF165 and PDGF-BB, were studied in
      the chick chorioallantoic membrane (CAM). The factors were air-dried on Thermanox
      discs and the inverted discs were placed on the day-13 CAM for a period of 3
      days. The specimens were then fixed, examined under a stereomicroscope and
      processed for semi- and ultrathin sectioning. VEGF165 induces marked vascular
      growth. Many new blood vessels emerge from the precapillary arterioles, and a
      brush-like formation of vessels can be seen in this region. In the venous part of
      the vascular system, the formation of sinusoidal or lacunar vessels can be seen.
      Edema does not develop. PDGF-BB induces thickening of the CAM due to
      extracellular-matrix production and the proliferation or immigration of
      fibrocytes. These lie just beneath the ectodermal epithelium and are oriented
      parallel to it. Out of the four factors we have already studied (PDGF-BB,
      VEGF165, Angiogenin, bFGF), only VEGF165 specifically induces the growth of blood
      vessels.

PMID- 1384393
TI  - Cytokeratin expression and early lens development.
AB  - Immunohistochemical analysis of cytokeratins and vimentin in human, rabbit and
      rat lens epithelium during development revealed transient coexpression of both
      types of intermediate filaments. Cytokeratins were still detectable after the
      closure of the lens vesicle (rat and rabbit embryos 13 days post conception) and
      in the epithelial cells located at the anterior side of the lens in 7-week-old
      human embryos. Different monoclonal antibodies against cytokeratin 8 reacted
      differently in lens cells but not in other embryonic tissues. In addition, early
      human and rabbit specimens exhibited cytokeratin immunostaining in the
      neuroectodermal cells of the eye cup as well as in the surrounding mesenchyme,
      and in the hyaloid artery. Possible explanations for the loss of cytokeratins
      during the differentiation of ectodermal and neuroectodermal cells are discussed.

PMID- 1384394
TI  - HNK-1 expression pattern in normal and bis-diamine induced malformed developing
      rat heart: three dimensional reconstruction analysis using computer graphics.
AB  - The spatiotemporal distribution of the immunoreactivity of monoclonal antibody
      HNK-1 was investigated immunohistochemically in normal and bis-diamine-induced
      malformed rat embryonic hearts using three-dimensional reconstruction with
      computer graphics. First recognized in the primitive heart 11.5 days after
      conception, HNK-1 immunoreactivity was distributed in the atrio-ventricular and
      bulbo-ventricular junctional areas with incomplete ring-like appearance in the
      early embryonic stages. In the late embryonic stages the immunoreactive sites
      were rearranged and localized in the sites topographically corresponding to
      almost the entire pathway of the conduction system, including the three major
      internodal tracts connecting the right sinoatrial node and atrioventricular node.
      Immunoreactivity gradually decreased after the completion of the conduction
      system, and only a faint reactivity in the atrio-ventricular node region remained
      in the new-born heart. These results indicate that HNK-1 is expressed temporarily
      in the pathways corresponding to the conduction system during the development of
      the heart. In bis-(dichloroacethyl)-octamethylen-diamine (bis-diamine)-induced
      malformed hearts, localization of HNK-1 immunoreactivity was not remarkably
      altered in the early embryonic heart. In the late embryo, immunoreactive sites in
      the sino-atrial node region and atrio-ventricular node region deviated
      dorsocaudally with the poorly developed internodal tracts, and abnormal
      distribution was observed in the bilateral atria. We consider that these
      abnormalities may occur in conjunction with abnormal morphological development
      such as insufficient absorption of the sinus venosus.

PMID- 1384395
TI  - A comparative study on the effects of tumor necrosis factor-alpha (TNF-alpha),
      human angiogenic factor (h-AF) and basic fibroblast growth factor (bFGF) on the
      chorioallantoic membrane of the chick embryo.
AB  - The chorioallantoic membrane (CAM) assay is a widely used bioassay for testing
      angiogenic activities. In the present study we compared the gross and
      micromorphological effects of three angiogenic factors applied in Elvax carriers
      on the CAM: Tumor necrosis factor-alpha (TNF-alpha), human angiogenic factor (h
      AF), and basic fibroblast growth factor (bFGF). Our question was whether the CAM
      responds to these factors which have very different actions with a stereotype or
      with a factor specific reaction. By microangiography and light microscopy, all
      positive reactions appeared as a spoke-wheel vascular pattern with a bundle of
      small capillary blood vessels in the center. These vessels were predominantly of
      a distended type in h-AF and TNF experiments, while narrower capillary vessels
      followed bFGF application. Chorioallantoic ectoderm and endoderm were thickened
      by cell accumulation and the mesenchymal stroma of the CAM was edematous and
      infiltrated with leucocytes in all three reactions. Additionally, bFGF
      experiments showed areas of densely arranged fibroblasts. Observations in vivo
      showed chorioallantoic tissue movements as a possible mechanism for the
      spokewheel vascular pattern. As compared with our results from studies of
      cytokinetics with bromodeoxyuridine, these current findings indicate that
      chemotaxis is responsible for the chorioallantoic angiogenic reaction rather than
      cellular proliferation.

PMID- 1384396
TI  - Migration and distribution of circumpharyngeal crest cells in the chick embryo.
      Formation of the circumpharyngeal ridge and E/C8+ crest cells in the vertebrate
      head region.
AB  - The cardiac neural crest is located in a transitional area on the neuraxis
      between trunk and cephalic regions and gives rise to both the dorsolateral and
      ventrolateral crest cell populations. Around stage 18 of chick development, a
      mass of E/C8+ cells surrounds the postotic pharyngeal arches and forms a crescent
      shaped arch, termed the circumpharyngeal ridge. Using immunohistochemistry and
      quail-chick chimeras, it was determined that the E/C8+ cell mass located in the
      circumpharyngeal ridge derives from the dorsolateral component of the cardiac
      neural crest. The ventrolateral cell population of the cardiac crest is located
      more medially and shows long-persistent HNK-1 immunoreactivity dorsolateral to
      the foregut. The crest cells that populate the gut arise from the caudal portion
      of the circumpharyngeal crest and are always located caudal to the caudal-most
      pharyngeal ectomesenchyme. Circumpharyngeal crest cells continuously populate the
      pharyngeal arch ectomesenchyme and enteric nervous system on the lateral side of
      the foregut wall, as well as the hypoglossal pathway which develops within the
      ventral portion of the circumpharyngeal ridge. E/C8 and HNK-1 immunoreactivity
      are associated with the cells migrating via the dorsolateral (circumpharyngeal)
      and ventrolateral pathways, respectively, with one exception: there is a
      population of putative crest cells along the proximal course of the vagal
      intestinal branch that shows both immunoreactivities around stage 20. DiI
      labeling of the cells in the circumpharyngeal ridge suggests that the cells are
      contributed from the circumpharyngeal ridge to this population. Thus, the
      distribution of the circumpharyngeal crest cells and their derivatives coincides
      with the peripheral branch distribution of the cranial nerves IX, X, and XII,
      whose development is selectively affected in the absence of the cardiac neural
      crest, the source of the circumpharyngeal crest.

PMID- 1384397
TI  - Epidural patient-controlled analgesia: influence of bupivacaine and hydromorphone
      basal infusion on pain control after cesarean delivery.
AB  - Epidural administration of hydromorphone was evaluated using a patient-controlled
      analgesia (PCA) delivery system in 170 healthy women undergoing elective cesarean
      delivery with epidural bupivacaine who were randomly assigned to one of four
      epidural PCA treatment groups: group I, hydromorphone alone by bolus
      administration; group II, hydromorphone, with a continuous (basal) infusion;
      group III, hydromorphone in combination with 0.08% bupivacaine by bolus
      administration; or group IV, hydromorphone and bupivacaine, with a concurrent
      infusion of both drugs. Patients in group I required significantly less opioid
      medication (2.1 +/- 1.1 mg [mean +/- SD]) during the first 24 h than patients in
      group II (3.3 +/- 1.3 mg). Similarly, patients in group III self-administered
      significantly less hydromorphone (2.0 +/- 1.0 mg) and bupivacaine (23.3 +/- 11.4
      mg) during the first 24 h of PCA therapy, compared with patients in group IV
      (hydromorphone [2.7 +/- 1.1 mg] and bupivacaine [31.5 +/- 11.6 mg]). The
      concomitant use of a local anesthetic or basal opioid infusion with hydromorphone
      via epidural PCA did not decrease the number of PCA demands or delivered doses.
      In addition, patients in all four groups had similar pain, sedation, discomfort,
      fatigue, and anxiety scores. The frequency of awakening at night to self
      administer analgesic medication was not decreased when a basal infusion was
      used.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384398
TI  - Free polymerized hemoglobin versus hydroxyethyl starch in resuscitation of
      hypovolemic dogs.
AB  - Polymerized bovine hemoglobin (PBH) was compared with hydroxyethyl starch (HES)
      in a hypovolemic shock model. Eighteen dogs were subjected to hemorrhage;
      systolic arterial blood pressure was maintained at 40 mm Hg for 30 min (mean
      blood pressure 37.8 +/- 4.7 [SD] mm Hg). Resuscitation was conducted by infusing
      their own shed blood (control group) or 6% HES (mol wt 200,000) in 0.9% NaCl (HES
      group) or PBH (PBH group), both in an equal amount to the shed blood. Directly
      after infusion, oxygen delivery and consumption returned to prehemorrhage levels
      in all three groups. In the HES group, the lowered arterial oxygen content was
      compensated by a 158% increase in cardiac output, in contrast to an increase of
      31% and 9%, respectively, in the control and PBH groups. Early recovery from
      hypovolemic shock with regard to oxygen transport and delivery in the PBH group
      seemed to be comparable to the control group, without the increase in cardiac
      output seen with HES infusion.

PMID- 1384399
TI  - Nitric oxide synthase inhibitor dose-dependently and reversibly reduces the
      threshold for halothane anesthesia. A role for nitric oxide in mediating
      consciousness?
AB  - Nitric oxide is a newly recognized cell messenger for the activation of soluble
      guanylate cyclase and is produced from L-arginine by the enzyme nitric oxide
      synthase in a wide variety of tissues, including vascular endothelium and brain.
      Inhalational anesthetics inhibit nitric oxide production from vascular
      endothelium and also decrease resting cyclic guanosine monophosphate content in
      multiple brain regions. Halothane has been shown to depress neurotransmission by
      L-glutamate and N-methyl-D-aspartate. These amino acid neurotransmitters are
      known to increase neuronal cyclic guanosine monophosphate content by stimulation
      of nitric oxide production. To investigate the possible involvement of the L
      arginine-to-nitric oxide pathway in the anesthetic state, the effect of a
      specific nitric oxide synthase inhibitor, nitroG-L-arginine methyl ester, on the
      minimum alveolar concentration (MAC) for halothane anesthesia was determined in
      Sprague-Dawley rats. Bolus injection of nitroG-L-arginine methyl ester at 0, 1,
      5, 10, 20, and 30 mg/kg resulted in a dose-dependent reduction in MAC for
      halothane of 0 +/- 0, 2.3 +/- 0.4, 21.5 +/- 3.9, 30.5 +/- 2.4, 51.0 +/- 7.8, and
      26.0 +/- 2.8%, respectively. NitroG-L-arginine methyl ester had no effect on MAC
      for halothane. Bolus infusion of L-arginine 300 mg/kg after MAC reduction by
      nitroG-L-arginine methyl ester 10 mg/kg resulted in an immediate and complete
      reversal of the MAC reduction. No reversal was observed after infusion of D
      arginine 300 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384400
TI  - [The role of lactate acidosis and enzyme hyperactivity in evaluating hypoxic
      organ disorders in patients following cardiopulmonary byoass].
AB  - One hundred and fifty patients after cardiopulmonary bypass surgery have been
      examined. It has been shown that overall enzyme activity should be taken into
      consideration when determining the genesis of postoperative hyperenzymemia and
      diagnosing the topical (organic) damage. High lactate level (6-8 mmol/l) reflects
      profound circulatory hypoxia and shows a great likelihood of secondary damage of
      parenchymatous organs in patients after cardiopulmonary bypass surgery. Marked
      lactatacidosis combined with a 5-10-fold increase in enzyme activity in the early
      postoperative period is an unfavourable prognostic sign. Prolonged antagosan
      (trasilol) administration during cardiopulmonary bypass surgery may be one of the
      techniques preventing and correcting hypoxic organ damage.

PMID- 1384401
TI  - New allelic fragments for parathyroid hormone-MspI in cattle.

PMID- 1384402
TI  - Alternaria spore and mycelium sensitivity in allergic patients: in vivo and in
      vitro studies.
AB  - Extracts from Alternaria spores and mycelia were prepared to evaluate their
      allergenic potencies in allergic patients. Twelve Alternaria-sensitive patients,
      with histories of rhinitis or asthma, were submitted to skin prick tests and five
      of 12 patients received nasal challenges with spores and mycelia. In vitro, the
      allergenic activity of each extract was determined by RAST, basophil histamine
      release and RAST-inhibition. All patients demonstrated skin reactivity to both
      extracts while skin reactivity to mycelia was higher than that induced by the
      spore extract (P < .005). Of the 12 patients, 11 had positive mycelia-RAST and
      9/12 had positive spore-RAST. It was found that mycelium-IgE antibody levels were
      higher than spore-IgE antibody levels (P < .005). Nine RAST-positive patients had
      positive histamine release tests (> 50%) and basophils challenged with mycelia
      appeared 10-fold more sensitive compared to the spore challenge. In four of five
      patients subjected to nasal provocation tests, immediate-type rhinitis was
      elicited either after spore or mycelium challenge. The patients exhibited a
      higher nasal reactivity with the mycelium challenge than with spores. RAST
      inhibition studies demonstrated that mycelial extracts shared common allergens
      with spore. These results indicated that Alternaria spore and mycelium were
      potent allergens in allergic patients and there was a variability in the pattern
      of in vivo and in vitro reactions between the patients for each allergen.

PMID- 1384403
TI  - A model of ion channel kinetics based on deterministic, chaotic motion in a
      potential with two local minima.
AB  - Models of the gating of ion channels have usually assumed that the switching
      between the open and closed states is a random process without a mechanistic
      basis. We explored the properties of a deterministic model of channel gating
      based on a chaotic dynamic system. The channel is modeled as a nonlinear
      oscillator, that has a potential function with two minima, which correspond to
      the stable open and closed states, and is driven by a periodic driving force. The
      properties of the model are like some properties of single channel data and
      unlike other properties. The model is like the data in that: the current switches
      between two well-defined states, this switching is nonperiodic, and there are
      subconductance states. These subconductance states are subharmonic resonances,
      due to the nonlinearities in the equation of the model, rather than stable
      conformational states due to local minima in the potential energy. The model is
      not like the data in that the current fluctuates too much within in each state
      and there are sometimes periodic fluctuations within a state. At the present
      time, the selection of the most appropriate channel model (Markov, chaotic, or
      other) is not possible, and in addition to chaotic models, other nonlinear models
      may be suitable.

PMID- 1384404
TI  - Characterization of monoclonal antibodies against Actinobacillus pleuropneumoniae
      serotype 5.
AB  - Two monoclonal antibodies against Actinobacillus pleuropneumoniae serotype 5,
      designated as 5MAb-1 and 5MAb-6, were characterized. Enzyme-linked immunosorbent
      assay-inhibition tests with whole-cell antigens obtained from strains of serotype
      1 through 12 of A pleuropneumoniae revealed that 5 MAb-1 bound to only serotype-5
      strains. The epitope recognized by 5MAb-1 was a carbohydrate that was sensitive
      to periodate oxidation and resided on the structure of beta-1,6-linked D
      galactose in an O-antigen polysaccharide of serotype-5 lipopolysaccharide.
      Analysis of these results revealed that the O-antigen polysaccharide of
      lipopolysaccharide was 1 of the antigenic determinants responsible for the
      serotype specificity of A pleuropneumoniae. On the other hand, 5MAb-6 reacted
      with strains of serotype 1 through 10 in varying degrees and its epitope was
      located on polypeptides sensitive to proteinase K. In an immunoblotting analysis,
      5MAb-6 reacted with 2 polypeptide bands, with molecular weights of approximately
      41,500 and 28,000, in the outer membrane protein-rich fraction obtained from
      strains of serotype 1 through 10. These results indicated that outer membrane
      proteins from several serotype strains of A pleuropneumoniae possessed common
      antigenic determinants.

PMID- 1384405
TI  - Morphologic and cytochemical characteristics of blood cells from the desert
      tortoise (Gopherus agassizii).
AB  - Morphologic and cytochemical staining characteristics of erythrocytes,
      leukocytes, and thrombocytes of the desert tortoise (Gopherus agassizii) were
      evaluated, using blood smears prepared from 23 healthy tortoises of Kern County,
      Calif. Special emphasis was placed on differentiating features of the various
      leukocytes and thrombocytes. A variety of cytochemical stains, including
      benzidine peroxidase, Sudan black B, chloroacetate esterase, alpha-naphthyl
      butyrate esterase, acid phosphatase, leukocyte alkaline phosphatase, periodic
      acid-Schiff, and toluidine blue were used. Heterophils had a characteristic,
      large, focal area of positive staining with chloroacetate esterase, alpha
      naphthyl butyrate esterase, and acid phosphatase. Eosinophils stained diffusely
      positive with benzidine peroxidase, allowing differentiation of this leukocyte
      from heterophils. Thrombocytes stained focally positive with periodic acid
      Schiff, allowing differentiation of these cells from lymphocytes, which stained
      uniformly negative. An intracytoplasmic body, commonly observed within
      erythrocytes, was considered ultrastructurally to represent a degenerate
      organelle.

PMID- 1384406
TI  - Mechanism of tetracycline-hydrochloride-induced pleurodesis. Tetracycline
      hydrochloride-stimulated mesothelial cells produce a growth-factor-like activity
      for fibroblasts.
AB  - Intrapleural instillation of tetracycline hydrochloride (TCN) is an effective
      means of achieving pleural fibrosis. However, its mechanism of action remains
      unknown. To evaluate the hypothesis that TCN stimulates pleural mesothelial cells
      to release growth-factor-like activity for fibroblasts we performed the following
      experiments. Rat visceral pleural mesothelial cells were incubated with TCN at
      doses ranging from 0.01 microgram/ml to 100 mg/ml. The conditioned media (CM)
      were collected after incubation for 2 to 48 h. CM caused fibroblasts to increase
      incorporation of thymidine when compared with CM that was unexposed to TCN (p
      less than 0.05). This growth-factor-like activity continued to be produced by
      mesothelial cells for 48 h after removal of TCN from the medium. There was a dose
      response relationship since increasing doses of TCN to as much as 1 mg/ml caused
      increasing production of growth-factor-like activity without mesothelial cell
      injury as measured by trypan blue exclusion. The growth factor activity was a
      competence-type activity. It coeluted with human PDGF at a molecular weight of
      31,000. It was heat-stable (100 degrees C for 10 min) and sensitive to trypsin
      and papain but not to heat-inactivated trypsin. Addition of cycloheximide or
      actinomycin D inhibited its production. TCN did not have any direct effect on
      fibroblasts. Bleomycin CM did not contain growth-factor-like activity for
      fibroblasts. These data demonstrate that TCN stimulates mesothelial cells to
      release a growth-factor-like activity for fibroblasts. This phenomenon may play
      an important role in TCN-induced pleural fibrosis.

PMID- 1384408
TI  - Early markers of pancreas transplant rejection.
AB  - To compare the predictive value of urinary amylase (UA), urinary insulin (UI),
      and urinary prostaglandin (PGE2), whole pancreas isografts or allografts from
      (ACI rat donors, RT1a) with bladder drainage of exocrine secretions were
      performed in Lewis rats (RT1(1)) with streptozotocin-induced diabetes. UA, UI,
      PGE2 and plasma glucose levels were measured daily. Euglycemia was restored on
      Postoperative Day 1 in all the recipients of isografts (N = 6) and was maintained
      for over a year. UI concentrations and PGE2 outputs were stable, with low levels
      ranging between 0.3 +/- 0.2 to 7 +/- 2 ng/ml and 56 +/- 15 to 164 +/- 48 ng/24
      hr, respectively, while UA levels were significantly elevated compared to normal
      controls (> 1,000 U/ml vs 29 +/- 16 U/ml). In the allograft group (N = 12),
      rejection occurred on Days 7 through 9, with a mean graft survival time of 8.1 +/
      0.1 days. UA dropped from a post-transplant peak of 2,422 +/- 353 U/ml on
      Postoperative Day 4 to below 1,380 +/- 256 U/ml 3 days before rejection (Day -3).
      UI increased to 83 +/- 16 ng/ml (P < 0.05) on Day -6 and reached a post
      transplant peak of 140 +/- 24 ng/ml on Day -5, while PGE2 output rose from a
      pretransplant level of 18 +/- 2 to 92 +/- 25 ng/24 hr on Postoperative Day 1,
      followed by a significant elevation on Day 4 (-4).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1384407
TI  - Pharmacologic and neurochemical evidence for the activation of capsaicin
      sensitive sensory nerves by lipoxin A4 in guinea pig bronchus.
AB  - Exogenous administration of lipoxin A4 (LXA4) to guinea pig isolated bronchus
      produced contractile effects in a concentration-dependent manner (1, 3, and 6
      microM). These responses were potentiated when preparations were previously
      incubated with thiorphan (10 microM), an inhibitor of tachykinin breakdown, but
      were significantly depressed when sensory nerves were previously desensitized in
      vitro by capsaicin (10 microM for 15 min) challenge. Ruthenium red (10 microM for
      20 min), a blocker of the cationic channel coupled to the capsaicin receptor,
      also produced, although in a weaker manner, a reduction in bronchomotor responses
      elicited by LXA4. On the other hand, preexposure to omega-conotoxin (0.1 microM
      for 45 min), a blocker of neuronal voltage-dependent Ca2+ channels, did not
      modify the LXA4 contractile effects. Furthermore, LXA4 (6 microM) superfusion of
      guinea pig bronchial tissue elicited a significant calcitonin gene-related
      peptide-like immunoreactivity (CGRP-LI) release that was reduced by capsaicin (10
      microM, 30 min) desensitization. Finally, LXA4 (10 microM) was unable to displace
      [3H]resiniferatoxin binding in dorsal root ganglion of rat and guinea pig. These
      findings support (1) a role for LXA4 in activating motor sensory function of
      capsaicin-sensitive nerves; (2) this activation mechanism is marginally ruthenium
      red-sensitive and omega-conotoxin-resistant; and (3) the interaction does not
      involve the recognized binding site on the vanilloid receptor. As a whole this
      study presents LXA4 as an endogenous mediator activating sensory nerves
      potentially involved in basic mechanisms of airway diseases.

PMID- 1384410
TI  - The Sweet syndrome or G-CSF reaction?

PMID- 1384409
TI  - [Clinical polymorphism of the XYY syndrome].
AB  - The XYY syndrome presents with a wide variation in the clinical features, both of
      the physical and behavioral nature. We report two new cases which illustrate this
      statement. The first case presented with aggressive behaviour and cryptorchidism.
      The second case was associated with pathological short height, pubertal delay and
      cardiac features (extrasystoles and short PR interval). We revise some of the
      aspects of XYY syndrome.

PMID- 1384411
TI  - The premature ventricular complex as a diagnostic aid.
AB  - Premature ventricular complexes (PVCs) can provide clues to the physical or
      electrocardiographic diagnosis through the associated compensatory pause, the
      break in the regularity of the rhythm, or the morphology of the PVC itself. A PVC
      may allow visualization of the P wave or of atrial flutter waves that would
      otherwise be obscured in the electrocardiogram. It can also be useful in
      distinguishing an S3 gallop from an S4 gallop. The compensatory pause that
      follows a PVC may allow normal conduction of the next QRS complex in a patient
      with a rate-dependent intraventricular conduction defect, and this normalized QRS
      complex may contain important diagnostic findings. A PVC can also reveal a
      myocardial infarct pattern when the sinus complex fails to do so. Although the
      need to treat PVCs is currently being de-emphasized, their diagnostic utility
      should not be overlooked.

PMID- 1384412
TI  - Production of rat stem cell factor from BRL cells by microcarrier perfusion
      culture.

PMID- 1384413
TI  - Bioremediation of soils contaminated with pentachlorophenol.

PMID- 1384414
TI  - Type I allergy in the inner ear of the guinea pig.
AB  - Guinea pigs were passively sensitized by sera containing antidinitrophenyl
      reaginic antibody and specifically challenged by dinitrophenyl-bovine serum
      albumin injected through the stylomastoid foramen. Nystagmus, head deviation,
      negative summating potentials on electrocochleography, and an increase of
      threshold and wave I peak latency on auditory brain stem response testing were
      observed after local challenge. These physiologic changes were reversible and
      resolved within several days. We also used Tranilast before the specific
      challenge. It is a blocking agent of chemical mediator release from mast cells.
      Negative summating potentials and head deviation were not observed after the use
      of this agent. In the animals that showed physiologic changes, we observed
      endolymphatic hydrops, mast cell degranulation, and eosinophil infiltration
      histologically in the challenged side of the inner ear. These results suggest
      that the physiologic and histologic changes provoked in the inner ear of the
      sensitized animals may have been induced by type I allergy.

PMID- 1384415
TI  - Plasma amylase estimation in recurrent abdominal pain in children.
AB  - In a prospective study of 50 children who were admitted on more than one occasion
      with undiagnosed abdominal pain, the serum amylase was found to be normal in
      every case. One case of acute pancreatitis was diagnosed in over 8000 admissions.
      Serum amylase estimation did not contribute to the management of children with
      recurrent abdominal pain, and acute pancreatitis is so rare that routine amylase
      estimations cannot be recommended in paediatric surgical practice.

PMID- 1384417
TI  - Cellular and humoral recognition of Toxoplasma gondii P30 antigen and its
      cleavage fragments.

PMID- 1384416
TI  - Should endoscopic stenting be the initial treatment of malignant biliary
      obstruction?
AB  - Forty-two patients with biliary obstruction caused by a stricture had a
      diagnostic ERCP with subsequent insertion of a straight 10G endoprosthesis. These
      patients represented 70% of a cohort in which stent insertion had been attempted.
      The majority (63%) had pancreatic carcinoma, but 22% had malignant hilar
      obstruction. Five patients (12%) died within a few days of stent insertion; ERCP
      may have contributed to two deaths. Jaundice was relieved in all survivors.
      Median hospital stay was 6 days (range 2-32 days). After further investigation,
      nine patients were thought to be potentially curable and underwent laparotomy.
      Late complications after stent insertion alone included cholangitis (26%) and
      recurrent jaundice (28%). Only one patient developed gastric outlet obstruction
      and needed a gastroenterostomy. Median survival in the endoprosthesis group was
      11 weeks (range 2-84 weeks). Survival was longer for patients with bile duct (14
      weeks) rather than hilar strictures (6 weeks). Median survival after subsequent
      surgery was 40 weeks (range 4-80 weeks) with two long-term survivors. This study
      confirms that ERCP and stent insertion is a useful initial treatment for
      obstructive jaundice due to a biliary stricture, being both diagnostic and
      therapeutic. Subsequent evaluation for curative surgery is not precluded and in
      the majority of cases worthwhile palliation may be achieved by stenting alone.

PMID- 1384418
TI  - [Control of cytotoxic T cell responses].

PMID- 1384419
TI  - [The cellular immunity response to the gag protein of HIV-1].

PMID- 1384421
TI  - Myelin basic protein-specific T lymphocytes in multiple sclerosis and controls:
      precursor frequency, fine specificity, and cytotoxicity.
AB  - A panel of 90 myelin basic protein (MBP)-specific T-cell lines were derived from
      peripheral blood of eight patients with multiple sclerosis and four normal
      subjects. The precursor frequency of MBP-reactive T cells in peripheral blood
      mononuclear cells ranged from 10(-7) to 9 x 10(-7) (mean, 6.7 x 10(-7)) in the
      group of patients with multiple sclerosis and from 0.5 x 10(-7) to 9.8 x 10(-7)
      (mean, 5.6 x 10(-7)) in the control subjects. This difference between the two
      groups was not statistically significant (p greater than 0.1). These T-cell lines
      expressed exclusively CD3+CD4+CD8- phenotypes and were restricted predominantly
      by HLA-DR molecules. When tested with fragments and synthetic peptides of human
      MBP, these MBP-specific T-cell lines (45 lines for each group) displayed a
      limited heterogeneous pattern with a biased recognition to peptide 84-102 and the
      C-terminal peptide 149-171. The reactivity to the 84-102 region of MBP was
      associated with the HLA-DR2, DRw15 (DRw15,2) haplotype, whereas the recognition
      to peptide 149-171 did not correlate with a particular HLA-DR allele(s).
      Furthermore, the majority of T-cell lines (greater than 75%) were found to
      exhibit substantial cytotoxic activity against MBP-coated target cells, but
      showing no significant difference between these two groups. This MBP-dependent
      cytotoxicity was not associated with epitope specificities of the T-cell lines
      tested.

PMID- 1384420
TI  - A novel neuronal messenger molecule in brain: the free radical, nitric oxide.
AB  - Understanding of the organization and function of a newly identified neuronal
      messenger molecule, nitric oxide, has progressed rapidly. Nitric oxide synthase
      has been purified and molecularly cloned from brain. Its localization is
      exclusively neuronal and endothelial. The catalytic activity of nitric oxide
      synthase accounts for the NADPH diaphorase staining of neurons that are uniquely
      resistant to toxic insults and neurodegenerative disorders. Nitric oxide has
      diverse functions. In platelets it inhibits their aggregation, in macrophages it
      mediates cytotoxicity, and in blood vessels it acts as a vasodilator. In the
      nervous system nitric oxide may be the retrograde transmitter in long-term
      potentiation. It is the "neurotransmitter" of cerebral vasodilator nerves and the
      inhibitory "neurotransmitter" of the motor neurons of the intestines. Nitric
      oxide in situations of excessive production may function as a neurotoxin,
      suggesting a role for nitric oxide in neurodegenerative disorders.

PMID- 1384422
TI  - Bacterial toxin superantigens activate human T lymphocytes reactive with myelin
      autoantigens.
AB  - Some bacteria that are common human pathogens produce protein toxins that are
      potent activators of human T lymphocytes expressing certain types of T-cell
      receptors. In this study we examined the ability of staphylococcal toxins to
      stimulate human T lymphocytes that also recognized the myelin autoantigens myelin
      basic protein and proteolipid protein. T-cell populations responding to myelin
      basic protein or proteolipid protein were isolated from 4 subjects including 1
      individual with multiple sclerosis. All myelin antigen-specific T cells responded
      in proliferation studies to at least one of the nine superantigenic toxins used
      in this study. The superantigenic toxins were up to 7 x 10(5)-fold more potent in
      proliferation assays than the myelin antigens to which the T cells were initially
      sensitized. In addition, cytotoxic, myelin basic protein-reactive T lymphocytes
      lysed antigen-presenting cells incubated with superantigenic toxins. These
      findings demonstrate a mechanism by which some bacterial infections might produce
      activation of myelin basic protein- and proteolipid protein-reactive T
      lymphocytes and perhaps contribute to demyelinating disease in humans.

PMID- 1384423
TI  - Absence of "red man syndrome" in patients being treated with vancomycin or high
      dose teicoplanin.
AB  - Twenty-five febrile patients with a history of intravenous drug use who were
      receiving either vancomycin (15 patients) or teicoplanin (10 patients) as part of
      a multicenter, double-blind, randomized, clinical efficacy trial were enrolled,
      upon receipt of their first dose of antibiotic, into a study to evaluate the
      effect of 1 g of vancomycin and high-dose teicoplanin (30 mg/kg of body weight)
      on histamine release and the occurrence of "red man syndrome" (RMS). In addition,
      10 healthy volunteer subjects (HVS) were randomized to receive either 1 g of
      vancomycin intravenously or a saline infusion in a double-blind, crossover design
      study. Patients and HVS were observed for the presence of erythema, flushing,
      pruritus, and hypotension during and for up to 1 h postinfusion by a blinded
      investigator. Histamine concentrations in plasma were measured at baseline and
      during and after drug infusion. No significant differences were noted in baseline
      temperature between patients (vancomycin recipients, 102.3 degrees F [39.1
      degrees C]; teicoplanin recipients, 102.4 degrees F [39.1 degrees C]) or
      incidence of bacteremia (7 of 15 vancomycin recipients; 5 of 10 teicoplanin
      recipients). There were no significant differences in peak vancomycin
      concentrations in the sera of patients (40.8 micrograms/ml) and HVS (49.9
      micrograms/ml). There were no reactions consistent with RMS in any patient who
      received teicoplanin (0 of 10); there was a significant difference in the
      occurrence of RMS in patients in comparison with that in HVS (0 of 15 patients, 9
      of 10 HVS; P less than 0.001) who received vancomycin. The predominant reaction
      was erythema and pruritus. Histamine concentrations in plasma and the area under
      the histamine plasma concentration-time curve were highly variable within groups
      and were not statistically different between patients and HVS. The incidence of
      RMS secondary to vancomycin or teicoplanin in our patient population appears to
      be low and consistent with clinical observations. Similar to previous
      investigations, RMS secondary to vancomycin in HVS was high (90%). However, we
      found no relationship between the histamine concentration in plasma or the area
      under the plasma histamine concentration-time curve and the severity of RMS in
      HVS. The reason for the discrepancy of RMS in patients versus that in HVS in
      unknown, but it may be related to a blunted effect of glycopeptides to produce
      the reaction in the presence of infection or it may be specific to our patient
      population.

PMID- 1384424
TI  - Anti-human immunodeficiency virus activity of a novel synthetic peptide, T22
      ([Tyr-5,12, Lys-7]polyphemusin II): a possible inhibitor of virus-cell fusion.
AB  - More than 40 peptides associated with tachyplesin and polyphemusin, which are
      highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus
      and Limulus polyphemus, were synthesized. Among these peptides, we found that a
      novel compound, which was called T22 ([Tyr-5,12, Lys-7]polyphemusin II), strongly
      inhibited the human immunodeficiency virus type 1 (HIV-1)-induced cytopathic
      effect and viral antigen expression. Its 50% effective concentration was 0.008
      micrograms/ml, while its 50% cytotoxic concentration was 54 micrograms/ml. The
      anti-HIV activity of T22 was observed with several strains of HIV-1, including
      zidovudine-resistant strains, and with HIV-2 within the concentration range of
      0.006 to 0.071 microgram/ml. T22 efficiently inhibited giant cell formation on
      the cocultivation of MOLT-4/HIV and MOLT-4 cells but modestly inhibited direct
      HIV binding. T22 did not inhibit reverse transcriptase activity. A time-of
      addition study, which involved monitoring of the appearance of proviral DNA by
      using the polymerase chain reaction technique, found that T22 exerted its effect
      on a process, most probably virus-cell fusion or uncoating, immediately after
      virus adsorption.

PMID- 1384425
TI  - Effects of (-)-2'-deoxy-3'-thiacytidine (3TC) 5'-triphosphate on human
      immunodeficiency virus reverse transcriptase and mammalian DNA polymerases alpha,
      beta, and gamma.
AB  - (-)-2'-Deoxy-3'-thiacytidine (3TC) is a selective inhibitor of human
      immunodeficiency virus replication in vitro (J. A. V. Coates, N. Cammack, H. J.
      Jenkinson, A. J. Jowett, M. I. Jowett, B. A. Pearson, C. R. Penn, P. L. Rouse, K.
      C. Viner, and J. M. Cameron, Antimicrob. Agents Chemother. 36:733-739, 1992). The
      effect of 3TC 5'-triphosphate on both the RNA-dependent and DNA-dependent
      activities of human immunodeficiency virus type 1 reverse transcriptase and DNA
      polymerases alpha, beta, and gamma from HeLa cells was investigated. 3TC 5'
      triphosphate is a competitive inhibitor (with respect to dCTP) of the RNA
      dependent DNA polymerase activity (apparent Ki = 10.6 +/- 1.0 to 1.24 +/- 5.1
      microM, depending on the template and primer used); the DNA-dependent DNA
      polymerase activity is 50% inhibited by a 3TC 5'-triphosphate concentration of
      23.4 +/- 2.5 microM when dCTP is present at a concentration equal to its Km
      value. Chain elongation studies show that 3TC 5'-triphosphate is incorporated
      into newly synthesized DNA and that transcription is terminated in a manner
      identical to that found for ddCTP. The 50% inhibitory concentrations of 3TC 5'
      triphosphate against DNA polymerases alpha, beta, and gamma at concentrations of
      dCTP equal to the Km were 175 +/- 31, 24.8 +/- 10.9, and 43.8 +/- 16.4 microM,
      respectively. More detailed kinetic studies with 3TC 5'-triphosphate and DNA
      polymerases beta and gamma are consistent with the fact that inhibition of these
      enzymes by 3TC 5'-triphosphate is competitive with respect to dCTP. The values of
      Ki were determined to be 18.7 microM for DNA polymerase beta and 15.8 +/- 0.8
      microM for DNA polymerase gamma.

PMID- 1384426
TI  - Methylation of HSV-1 DNA as a mechanism of viral inhibition: studies of an
      analogue of methyldeoxycytidine: trifluoromethyldeoxycytidine (F3mdCyd).
AB  - Although several hypomethylating agents such as 5-azadeoxycytidine and 5
      fluorodeoxycytidine have been shown to activate transcription after incorporation
      into viral or cellular DNA, agents which selectively affect the methylation
      status of virus-infected cells have not been described. Studies on the antiviral
      effect of the methyldeoxycytidine (mdCyd) analogue trifluoromethyldeoxycytidine
      (F3mdCyd) showed significant antiviral activity against herpes simplex virus type
      1 (HSV-1). This analogue of both dCyd and dThd is selectively incorporated into
      the DNA of herpesvirus infected cells due to the unique specificity of the
      herpesvirus thymidine kinase (TK) because the HSV-1 TK is both a dCyd and dThd
      kinase. In contrast, the deoxycytidine kinase of uninfected cells preferentially
      phosphorylates dCyd and has a poor affinity for F3mdCyd. F3mdCyd hemisubstituted
      M13 DNA displayed the same properties as mdCyd-substituted M13 DNA with respect
      to cleavage by restriction enzymes, and acted as an efficient template for
      eukaryotic DNA methyltransferase (S-adenosyl-L-methionine DNA (cytosine-5)
      methyltransferase: EC 2.1.1.37). Using the persistently infected CEM cell model
      system, the extent of DNA methylation was shown to increase in a dose-related
      manner when HSV-1-infected CEM cells were treated with increasing concentrations
      of F3mdCyd. Higher levels of methylation correlated with significant decreases in
      HSV-1 titers. Isoschizomer analyses followed by Southern blotting and
      hybridization with genomic HSV-1 DNA showed that DNA from HSV-1-infected,
      analogue-treated Vero cells was resistant to cleavage by restriction enzymes at a
      time when productive virus was not present in culture. We infer from these
      results that the methylation-like properties of the incorporated F3mdCyd occur
      concomitantly with, and appear to be involved in, the mechanisms of the
      analogue's antiviral effect towards HSV-1.

PMID- 1384427
TI  - In vitro selection of human immunodeficiency virus type 1 resistant to 3'-azido
      3'-deoxythymidine.
AB  - 3'-Azido-3'-deoxythymidine (AZT)-resistant human immunodeficiency virus type 1
      (HIV-1) was obtained by growing HTLV-IIIB in C8166 cell cultures in the presence
      of inhibitory concentrations of AZT. The AZT-resistant HIV-1 was capable of
      replicating, as measured by infectious virus yield, and inducing cytopathic
      effect in the presence of AZT concentrations able to completely suppress the
      replication of parental HTLV-IIIB. Cloning of the AZT-resistant HIV-1 revealed
      that a number of different variants of HIV-1 with various degrees of sensitivity
      to AZT emerged during propagation of HTLV-IIIB in C8166 cells in the presence of
      the drug. PCR experiments performed on DNA extracted from C8166 cells infected
      with a resistant strain revealed that viral DNA was produced in the presence of
      inhibitory concentrations of AZT, while viral DNA in C8166 cells infected with
      the parental virus was drastically inhibited. Reverse transcriptase isolated from
      the AZT-resistant HIV-1 variant failed to show resistance to AZT 5'-triphosphate.

PMID- 1384428
TI  - Sulfonic acid polymers as a new class of human immunodeficiency virus inhibitors.
AB  - Four sulfonic acid polymers [poly(4-styrenesulfonic acid)(PSS),
      poly(anetholesulfonic acid)(PAS), poly(vinylsulfonic acid)(PVS), poly(2
      acrylamido-2-methyl-1-propanesulfonic acid)(PAMPS)] have been found to inhibit
      the cytopathicity of HIV-1 and HIV-2 in MT-4 cells at concentrations that are not
      toxic to the host cells. The sulfonic acid polymers also inhibited syncytium
      formation in co-cultures of MOLT-4 cells with HIV-1- or HIV-2-infected HUT-78
      cells. They also inhibited binding of anti-gp120 mAb to HIV-1 gp120 and blocked
      adsorption of HIV-1 virions to MT-4 cells. PSS and PAS, but not PVS and PAMPS,
      interfered with the binding of OKT4A/Leu3a to the CD4 receptor. The anti-HIV
      activity of these polyanionic compounds can be ascribed to inhibition of the
      gp120-CD4 interaction. Sulfonic acid polymers represent a lead of anti-HIV
      compounds that warrant further evaluation of their therapeutic potential.

PMID- 1384429
TI  - Post-hospitalization concerns of medical-surgical patients.
AB  - In response to the phenomenon of earlier-than-ever discharge, the post
      hospitalization concerns of medical-surgical patients were investigated in a
      descriptive survey conducted in physicians' offices and clinics. The 150 recently
      discharged patients typically identified multiple concerns including
      understanding their progress, activity, insurance, medications, and pain control.
      Differences were found in number of concerns according to age, gender, length of
      hospital stay, type of treatment (medical or surgical), and perceived presence or
      absence of discharge planning.

PMID- 1384430
TI  - Monoclonal antibodies directed against epitopes within the core protein structure
      of the large aggregating proteoglycan (aggrecan) from the swarm rat
      chondrosarcoma.
AB  - The core protein of the large hyaline cartilage proteoglycan, aggrecan, is
      composed of six distinct domains: globular 1 (G1), interglobular, globular 2
      (G2), keratan sulfate attachment, chondroitin sulfate (CS) attachment, and
      globular 3 (G3). Monoclonal antibodies that recognize epitopes in these domains
      were raised against Swarm rat chondrosarcoma aggrecan that was either denatured
      through reduction and alkylation or partially deglycosylated through
      chondroitinase ABC digestion or alkali elimination, the latter with or without
      sulfite addition. Monoclonal antibodies were further characterized for reactivity
      to purified aggrecan substructures including rat chondrosarcoma G1 and CS
      attachment domains, a recombinant rat chondrosarcoma G3 domain fusion protein,
      bovine articular cartilage G2 domain, and rat chondrosarcoma link protein (LP).
      Biochemical characterization of the specificities of these monoclonal antibodies
      indicated that one (1C6) recognized an epitope shared by both the G1 and the G2
      domains; one (5C4) recognized an epitope shared by both LP and the G1 domain; one
      (7D1) recognized an epitope shared by both the G1 and the CS attachment domains;
      two (14A1 and 15B2) recognized epitopes in the CS attachment domain; one (14B4)
      recognized an epitope in the G3 domain; and one (13D1) recognized a ubiquitous
      epitope shared by the G1, G2, G3, and CS attachment domains of aggrecan and also
      LP. Collectively the specificities of these antibodies confirm the occurrence of
      multiple repeated epitopes (both carbohydrate and protein in nature) throughout
      the different domain structures of aggrecan. These antibodies have been proven to
      be useful for identifying aggrecan-like molecules in several connective tissues
      other than cartilage.

PMID- 1384431
TI  - Characterization of a bifunctional peptidylglycine alpha-amidating enzyme
      expressed in Chinese hamster ovary cells.
AB  - Peptidylglycine alpha-amidating enzyme (alpha-AE) catalyzes the conversion of
      glycine-extended prohormones to their biologically active alpha-amidated forms.
      We have derived a clonal Chinese hamster ovary cell line that secretes
      significant quantities of active alpha-AE. Enzyme production was increased by
      selection for methotrexate-resistant cells expressing a dicistronic message.
      Amplification of the alpha-AE gene was monitored by Southern blot analysis,
      enzyme activity, and immunoreactive protein throughout the selection process. The
      soluble enzyme is bifunctional as determined by the ability to convert either the
      glycine-extended substrate, dansyl-Tyr--Val--Gly, or the intermediate, dansyl-Tyr
      -Val--alpha-hydroxyglycine, to the dansyl-Tyr--Val--NH2 product. The recombinant
      alpha-AE was purified by a simple two-step chromatographic process. The purified
      enzyme is partially glycosylated and the glycosylated and nonglycosylated forms
      of the enzyme were separated on a Con A-Sepharose column. The kinetic constants
      for dansyl-Tyr--Val--Gly, dansyl-Tyr--Val--alpha-hydroxyglycine, ascorbate, and
      catechol were the same for both forms of alpha-AE. In addition, mimosine is
      competitive vs ascorbate with K(is) = 3.5 microM for the nonglycosylated alpha-AE
      and K(is) = 4.2 microM for the glycosylated alpha-AE. Therefore, the presence or
      absence of asparagine-linked oligosaccharide does not affect the catalytic
      efficiency of the enzyme. Overexpression of the recombinant enzyme in CHO cells
      greatly enhances expression of the endogenous gene, implicating a feedback
      mechanism on the alpha-AE gene.

PMID- 1384432
TI  - Dual effects of oleic acid on Ca2+ mobilization and protein phosphorylation in
      human platelets in presence or absence of platelet activating factor.
AB  - This laboratory demonstrated earlier that oleic acid inhibited platelet
      activating factor (PAF)-induced aggregation and serotonin release of rabbit
      platelets (M. Miwa, C. Hill, R. Kumar, J. Sugatani, M. S. Olson, and D. J.
      Hanahan, 1987, J. Biol. Chem. 262, 527-530). More recently, we reported that
      oleic acid caused a decrease in phosphatidylinositol-4-phosphate (PIP) and
      phosphatidylinositol-4,5-bisphosphate (PIP2), but did not affect the level of
      inositol-1,4,5-trisphosphate (IP3), in rabbit platelets (D. Nunez, J. Randon, C.
      Gandhi, A. Siafaka-Kapadai, M. S. Olson, and D. J. Hanahan, 1990, J. Biol. Chem.
      265, 18330-18838). These results suggested that oleic acid did not stimulate
      phospholipase C. In contrast, PAF induced a decrease in PIP2 and an increase in
      PIP level and IP3. These effects were shown to be attenuated by oleic acid. In
      this current study, our experiments show that (a) oleic acid blocked PAF-induced
      rise in intracellular [Ca2+] (to provide a mechanism in agreement with our
      previous experiments which showed that oleic acid inhibited PAF-induced IP3 rise
      in platelets) and (b) oleic acid itself induced a gradual rise in [Ca2+]i, which
      would provide a mechanism for oleic acid-induced aggregation despite the fact
      that oleic acid did not cause the production of IP3 (Nunez et al., 1990). Oleic
      acid, in a dose-dependent manner, was shown to inhibit PAF-induced Ca2+
      mobilization from intra- and extracellular sources. The inhibition was closely
      related to the suppressive effect of oleic acid on PAF-induced aggregation.
      Furthermore, oleic acid inhibited the PAF-stimulated phosphorylation of the 20-
      and 40-kDa proteins. At concentrations above 20 microM, oleic acid itself could
      induce platelet aggregation and Ca2+ mobilization, but the time sequence of these
      two responses in human platelets was significantly different from those obtained
      with PAF. Oleic acid alone, at 20 microM, caused a 1.4-fold increase in the cAMP
      level in platelets which was followed by a decline to a basal value at higher
      concentrations of this fatty acid. It seemed clear that elevation of adenylate
      cyclase activity was not associated with free fatty acid inhibition of platelet
      activation. Interestingly, both PAF and oleic acid added separately to human
      platelets induced protein-tyrosine phosphorylation, but oleic acid did not cause
      any inhibition of PAF-induced protein-tyrosine phosphorylation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1384433
TI  - Rat cystathionine beta-synthase: expression of four alternatively spliced
      isoforms in transfected cultured cells.
AB  - The gene for rat cystathionine beta-synthase consists of 17 exons. Its
      transcripts are alternatively spliced, forming four distinct mRNA species. Type
      III consists of exons 1 through 12, 14, 15, and 17; type I also contains exon 16.
      The open reading frame of type IV spans exons 1-->13; type II, 3-->13. We cloned
      the corresponding cDNAs into appropriate expression vectors and inserted the
      constructs into Escherichia coli (I, III, and IV) and Chinese hamster (CH) cells
      (I through IV); all sequences were transcribed and translated. Catalytic activity
      was observed only for types I and III in lysates of transfected CH cells and
      transformed E. coli. The catalytic and kinetic properties of I and III were
      identical despite their structural difference (exon 16). Both isoforms exhibited
      6 mM Km constants for homocysteine which were reduced approximately eightfold by
      AdoMet; this elucidates the mechanism by which AdoMet regulates synthase
      activity. The four isoforms were differentially degraded by transfected cultured
      cells. Type III (t1/2 = 18 h) was degraded at 1/3 the rate of type I (t1/2 = 6
      h); thus the 14 amino acid residues encoded by exon 16 appear to enhance
      degradation of CBS. The half-lives of both types II and IV were markedly shorter
      (ca. 1 h). Western blots comparing rat liver to lysates from transfected CH cells
      revealed that hepatocytes express both isoforms. Type III was predominant, as
      predicted by its longer half-life and more abundant mRNA. PCR analysis of cDNA
      from various tissues revealed that type III mRNA was preferred in liver, kidney,
      and heart; equal amounts of I and III were found in brain.

PMID- 1384434
TI  - Hexachlorocyclohexane pesticides reduce survival and alter plasma membrane
      structure of Chinese hamster V79 cells.
AB  - We studied the cytotoxic effects of alpha-, beta-, gamma-, and delta
      hexachlorocyclohexanes (HCCH) on the survival of Chinese hamster V79 cells using
      clonogenic assays. Lethal dose yielding 50% cell survival (LD50) suggests the
      following order of cytotoxicity: delta-(+)gamma-HCCH (LD50 4 micrograms/ml) (1:1,
      w/w, mixture) > delta-HCCH (LD50 6 micrograms/ml) > gamma-HCCH (LD50 13
      micrograms/ml) > alpha-HCCH (LD50 approx. 35 micrograms/ml) >> beta-HCCH.
      Structural changes in plasma membranes prepared from HCCH-treated V79 cells at
      dose yielding 10% cell survival (LD10) were analyzed using Raman spectroscopy.
      Raman spectra of plasma membranes show bands at 2850, 2880-2890, and 2935 cm-1 in
      the C-H stretching region. The plot of the ratio (I2880-2890/I2850) vs
      temperature for control plasma membranes shows two transitions between -5 and 5
      degrees C and between 12 and 20 degrees C. Plasma membranes prepared from gamma-
      and delta-HCCH-treated Chinese hamster V79 cells show single transitions between 
      4 and 11 degrees C and between -2 and 11 degrees C, respectively. These changes
      in the thermal transition properties suggest that both gamma- and delta-HCCH
      alter lipid and lipid-protein phases of the plasma membrane of V79 cells. Raman
      analysis of the amide I and amide III region spectra further suggest that delta
      HCCH also alters the secondary structure and the environment of highly amidated
      segments of plasma membrane proteins. We suggest that the primary action of
      biologically active HCCH isomers is to disrupt the organization of the plasma
      membrane and that may affect cell viability.

PMID- 1384435
TI  - Role of tyrosyl phosphorylation in neutrophil priming by tumor necrosis factor
      alpha and granulocyte colony stimulating factor.
AB  - The ability of human tumor necrosis factor-alpha (TNF-alpha) and human
      granulocyte colony stimulating factor (G-CSF) to induce phosphorylation of
      protein tyrosyl residues in human peripheral neutrophils (PMN) was investigated
      by Western blot analysis with antiphosphotyrosine antibody. Both TNF-alpha and G
      CSF increased the tyrosyl phosphorylation of various proteins, such as species of
      54-, 63-, 72-, 83-, 98-, 108-, and 115-kDa proteins. The ligand-stimulated
      tyrosyl phosphorylation of the 115-kDa protein was time- and concentration
      dependent. When the 115-kDa protein was phosphorylated, it was recovered from
      membrane fractions. The phosphorylation of the 115-kDa protein was inhibited by
      genistein and alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide (ST
      638), inhibitors of tyrosine kinase (TK), and was enhanced by 1-(5-isoquinoline
      sulfonyl) methyl-piperazine dihydrochloride (H-7) and staurosporine, inhibitors
      of Ca(2+)- and phospholipid-dependent protein kinase (PKC). Similar inhibition by
      the TK inhibitors and stimulation by the PKC inhibitors were also observed with
      formylmethionyl-leucyl-phenylalanine (FMLP)-induced superoxide (O2.-) generation
      by TNF-alpha- or G-CSF-primed PMN. Phosphorylation of the 115-kDa protein
      occurred in parallel with the ligand-dependent generation of O2.-. These and
      other observations suggested that substrate proteins for tyrosine kinase, such as
      the 115-kDa protein, might play critical roles in the mechanism for priming of
      neutrophils. This is the first report describing that tyrosyl phosphorylation is
      involved in the priming of neutrophils by G-CSF and TNF-alpha.

PMID- 1384436
TI  - [Recent advances in ovarian cancer chemotherapy].
AB  - The standard approach for epithelial ovarian cancer has been maximum
      cytoreductive surgery followed by combination therapy. Several prospective
      control studies individually failed to demonstrate improved survival advantage
      for the Adriamycin containing combination compare with cisplatin plus
      cyclophosphamide. The two drug combination of carboplatin plus cyclophosphamide
      will be thought to become the treatment of choice, because it is equally
      effective as and less toxic than a regimen of cisplatin plus cyclophosphamide.
      Clinical trials are also in progress with more dose-intense regimens based on
      considerable retrospective evidence that survival is correlated with the dose
      intensity of platinum compounds. Currently, high dose carboplatin plus Gm-CSF,
      two-drug combination of carboplatin and cisplatin and super high dose carboplatin
      combined with autologous bone marrow transplantation are undergoing clinical
      trials. Taxol and taxotere, most important cancer drugs after emergence of
      cisplatin compound, has been shown to have clinical activity in drug resistant
      ovarian cancer patients. Majority of patients even with advanced germ cell tumors
      of the ovary is now cured because of the development of effective platinum-based
      combination chemotherapy of PVB or BEP.

PMID- 1384438
TI  - [Symptomatic treatment of benign hypertrophy of the prostate. Comparative study
      of prazosin and serenoa repens].
AB  - Forty-five patients diagnosed as having BPH and clinically diagnosed micturition
      disorders were entered in a therapeutic protocol. Twenty-five patients received
      Prazosin and the remaining 20 patients were treated with Serenoa Repens for a
      period of 12 weeks. The symptomatology was assessed by flowmetry and the patients
      were questioned as to the irritative symptoms. It can be concluded from the study
      that Prazosin is slightly more effective in controlling the irritative symptoms
      produced by BPH.

PMID- 1384437
TI  - Cultured nail keratinocytes express hard keratins characteristic of nail and hair
      in vivo.

PMID- 1384439
TI  - Efficacy of eight serially measured markers for diagnosis of prostatic carcinoma.
AB  - In this study we measured eight different tumor markers (PSA, PAP, TPA, CEA, Ca
      50, Ca 19-9, Ca 125 and Ca 15-3) in 39 patients with prostatic adenocarcinoma and
      in 90 patients with benign prostatic hyperplasia. We then calculated the
      sensitivity and specificity for each tumor marker separately and found that only
      PSA, when we consider as normal value 10 ng/ml, has a sufficiently high
      sensitivity and specificity. Our conclusion is that only PSA can be used for
      diagnostic purposes in conjunction with other diagnostic modalities.

PMID- 1384440
TI  - Role of substance P in inflammatory arthritis.

PMID- 1384441
TI  - Characteristics of immunocompetent cells in synovial membranes from multiple
      sites in patients with rheumatoid arthritis.
AB  - The phenotypic characterization of enzymatically dissociated mononuclear cells in
      synovial membrane samples from multiple sites in two patients with rheumatoid
      arthritis (RA) were examined by fluorescence activated flow cytometry. In
      synovial membrane samples from each patient there was a consistent increase in
      the proportion of CD8+ cells (suppressor/cytotoxic), CD14+ cells
      (monocytes/macrophages), and HLA-DR+ cells compared with paired peripheral blood
      mononuclear cells. The proportion of CD4+ cells (helper/inducer) in synovial
      membrane was variable. Studies of in vitro production of IgM and IgM rheumatoid
      factor in one patient showed strikingly similar values for synovial membrane
      rheumatoid factor production at the two sites, which was enhanced compared with
      production in peripheral blood. These results suggest that in individual patients
      with RA the intra-articular immune response is comparable at multiple anatomical
      sites and that it is distinct from that in peripheral blood.

PMID- 1384442
TI  - Human cartilage proteoglycans as T cell autoantigens.

PMID- 1384444
TI  - Exocrine pancreatic function in mediastinal teratomata: an aid to preoperative
      diagnosis?
AB  - The diagnosis of teratoma may be made by demonstration of high amylase content in
      fluid aspirated from anterior mediastinal lesions. In 2 cases of mediastinal
      teratoma proteolytic enzyme activity was evident at the time of operation. A
      diagnosis of mediastinal teratoma was aided in 2 subsequent cases by
      demonstration of elevated amylase activity in the aspirated fluid before
      definitive operation.

PMID- 1384443
TI  - Intestinal transplantation in composite visceral grafts or alone.
AB  - Under FK 506-based immunosuppression, the entire cadaver small bowel except for a
      few proximal and distal centimeters was translated to 17 randomly matched
      patients, of whom two had antigraft cytotoxic antibodies (positive cross-match).
      Eight patients received the intestine only, eight had intestine in continuity
      with the liver, and one received a full multivisceral graft that included the
      liver, stomach, and pancreas. One liver-intestine recipient died after an
      intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16
      patients are alive after 1 to 23 months, in one case after chronic rejection,
      graft removal, and retransplantation. Twelve of the patients have been liberated
      from total parenteral nutrition, including all whose transplantation was 2 months
      or longer ago. The grafts have supported good nutrition, and in children, have
      allowed growth and weight gain. Management of these patients has been difficult
      and often complicated, but the end result has been satisfactory in most cases,
      justifying further clinical trials. The convalescence of the eight patients
      receiving intestine only has been faster and more trouble free than after liver
      intestine or multivisceral transplantation, with no greater difficulty in the
      control of rejection.

PMID- 1384445
TI  - Palliative intubation for dysphagia.

PMID- 1384446
TI  - Aprotinin treatment during open heart operation in a patient with severe
      thrombocytopenia.

PMID- 1384447
TI  - High-dose aprotinin in emergency coronary artery bypass after thrombolysis.

PMID- 1384448
TI  - Expanding wire stents in benign tracheobronchial disease: indications and
      complications.
AB  - Prosthetic tracheobronchial stents provide palliative treatment for narrowed
      airways where surgical resection is inadvisable. Over a 1-year period, 28
      Gianturco expanding wire stents were used in 15 patients for nonneoplastic
      indications: pure fibrous airway stenosis (6), fibroinflammatory stenosis (4),
      and tracheobronchial malacia (5). Insertion was technically straightforward. A
      satisfactory airway lumen with immediate improvement in ventilatory function was
      obtained in all patients. After insertion all patients had an irritation-type
      cough that either subsided spontaneously (10 patients) or was successfully
      suppressed with inhaled corticosteroid therapy (5 patients). The most common
      complication (12 patients) was granuloma formation leading to stent removal in 3
      patients with fibroinflammatory stenosis. Other complications were dysphagia (1),
      suction catheter entrapment (1), and fatal massive hemoptysis (1). At a mean
      follow-up of 13 months (range, 3 to 19 months) all remaining stents are
      functioning well with no displacement or infection. Overall results were
      satisfactory in pure fibrous stenoses and tracheobronchial malacia but poor in
      the presence of inflammation. Tracheobronchial wire stents can be successfully
      used in selected patients.

PMID- 1384449
TI  - Surgically created Wolff-Parkinson-White syndrome after Fontan operation.
AB  - The Wolff-Parkinson-White syndrome is caused by a congenital accessory connection
      between the atrium and ventricle. We describe a case of symptomatic Wolff
      Parkinson-White syndrome that arose after a Bjork modification of the Fontan
      operation. Invasive electrophysiologic and intraoperative mapping indicated that
      the surgically created atrioventricular connection was functioning as an
      accessory pathway. Surgical dissection and cryoablation abolished the symptoms
      and the preexcitation.

PMID- 1384450
TI  - [Study of possible biological transformation of kanamycin to amikacin].
AB  - For transformation of kanamycin A (Km) to amikacin (Ak) with acylating enzymes
      from B. circulans, a culture producing butirosin (Btn), cellular and acellular
      conversion systems and methods for chemical and biological identification of Km,
      Ak and Btn were developed. The level of conversion of Km to Ak in vivo and in
      vitro did not exceed 2 per cent.

PMID- 1384451
TI  - [Selection and physiological study of culture of Bacillus circulans-- producer of
      butirosin].
AB  - For isolating a highly active variant of the butirosin-producing culture, a
      strain forming trace amounts of the antibiotic substance was used. Exposure to
      nitrosomethylbiuret and nitrosoguanidine and the use of selective media
      containing streptomycin and butirosin resulted in a 30-fold increase in the
      strain productivity. Thin layer chromatography of the produced antibiotic
      substance in the solvent system developed by the authors, mass spectrometry and
      assay of the antimicrobial spectrum in regard to ++gram-positive and ++gram
      negative bacteria by using the known aminoglycosidine-inactivating enzymes
      revealed that the substance was identical to butirosin. Along with the major
      product, the fermentation broth contained up to 5 per cent of ribostamycin.

PMID- 1384452
TI  - Calcium channel modulators and susceptibility to ischaemic ventricular
      fibrillation: modification of cellular calcium overload.
AB  - The effects of the calcium channel modulators, Bay k 8644, infused i.v. at a rate
      of 2.5 micrograms/kg/min, and diltiazem, injected i.v. in a dose of 0.5 mg/kg, on
      the susceptibility to fibrillation induced by ischaemia, were investigated in
      anaesthetized, open-chest pigs. Ischaemia was produced, under ventricular pacing
      at constant high rate (180 beats/min), by transient complete occlusion of the
      left anterior descending coronary artery, near its origin. It was maintained till
      the triggering of fibrillation. The propensity to fibrillation was judged from
      the time elapsing between the onset of occlusion and the onset of fibrillation
      (time to fibrillation). In addition to the surface electrocardiogram, conduction
      time and monophasic action potential were recorded in the ventricular contractile
      fibres, as were dP/dtmax in the left ventricle and blood pressure in the carotid
      artery. At the end of a 10 min infusion, Bay k 8644 lowered to a large extent
      (about 40%) the time to fibrillation, which returned to its control values within
      the following 20 min. Conversely, diltiazem increased the time to fibrillation by
      a factor 4 or 5 at 5 min after its administration. This time to fibrillation
      remained substantially increased 25 min later. These changes were not associated
      with alterations in conduction time or monophasic action potential duration in
      the absence of ischaemia, but with significant alterations in myocardial
      contractility and blood pressure: in the direction of an increase with Bay k 8644
      and of a decrease with diltiazem. These results are in agreement with the
      enhancement by Bay k 8644 and the prevention by diltiazem of cell calcium
      overload which is at present recognized as being the essential determinant of the
      fibrillatory process.

PMID- 1384455
TI  - A modified Da Fano silver stain for demonstration of neurons and dendrites in
      glycol methacrylate-embedded brain tissue.
AB  - Golgi impregnation techniques are commonly used for characterization of neurons
      and their dendritic and axonal processes. Most of the widely used techniques
      require processing of fresh brain tissues, which limits the amount of material
      available for study. Additionally, the stained blocks must be subsequently
      embedded in paraffin, which produces considerable cellular shrinkage and
      distortion artifacts. Modification by one investigator of an early silver
      impregnation technique, designed to demonstrate the Golgi apparatus, allowed
      demonstration of neurons and their dendritic processes. Our further modification
      of the later technique, along with embedding of the stained tissue in glycol
      methacrylate, permits detailed examination of neurons and their processes in
      formaldehyde-fixed neonatal human brains. In cerebellar sections, this modified
      technique impregnates nearly all Purkinje cells, elucidating the fine structural
      detail of the developing neuronal dendritic tree and spines.

PMID- 1384453
TI  - Parathyroid hormone fragment 1-34 and anti-inflammatory effect.
AB  - We have studied the possible activity of the rat parathyroid hormone fragment 1
      34, peripherally or centrally injected, on the vascular permeability induced by
      local administration of croton oil. Our study considered also the possible
      interference of parathyroid hormone fragment 1-34 on the release of histamine by
      mast cells and on the content of histamine in paw tissue. Parathyroid hormone
      fragment 1-34 significantly reduced the increase in vascular permeability
      produced in mice by local croton oil injection, as well as the serotonin-induced
      paw edema in the rat. These effects of parathyroid hormone fragment 1-34 were
      present only after peripheral administration. At the dose of 3.3 micrograms/kg,
      it decreased the histamine content in paw tissue. Peripheral administration of a
      calcium antagonist, such as nimodipine, at the dose of 50 micrograms/kg, or a
      metal-chelating agent, such as ethylene-diaminetetraacetic acid, at the dose of
      10 micrograms/kg, antagonized the anti-inflammatory effect of parathyroid hormone
      fragment 1-34. Moreover, at 10-100 microliters/ml it significantly decreased the
      histamine release by mast cells.

PMID- 1384454
TI  - Cystadenoma and cystadenocarcinoma with mesenchymal stroma of the liver.
      Immunohistochemical analysis.
AB  - Cystadenoma with mesenchymal stroma is a rare neoplasm of the liver that occurs
      exclusively in young women and has a potential for malignant transformation. A
      light microscopic and immunohistochemical study of a case of biliary cystadenoma
      and another of biliary cystadenocarcinoma revealed a range of differentiation of
      the lining epithelial cells. The lining cells in the cystadenoma resembled the
      cells of the normal intrahepatic bile ducts. In contrast, the epithelial lining
      in the case of cystadenocarcinoma had features of intestinal mucosa, including
      goblet, Paneth, and endocrine cells similar to those found in other mucinous
      cystic neoplasms of the foregut area. The compact "ovarianlike" mesenchymal
      stromal cells had immunohistochemical characteristics of myofibroblasts. These
      are reactive contractile cells that may proliferate in response to the expanding
      cysts and female hormones, and they differ immunohistochemically from ovarian
      stromal cells.

PMID- 1384456
TI  - Expression of P-glycoprotein in normal muscle cells and myogenic tumors.
AB  - We have analyzed the expression of the multidrug resistance (mdr-1) gene product,
      P-glycoprotein, by immunohistochemical staining of frozen tissue sections of
      human normal muscle fibers and 31 tissue specimens of cases of myogenic sarcomas.
      The objective of this study was to further characterize what appears to be a
      variety of responses to therapy in like-appearing but distinct tumors. We have
      used two mouse monoclonal antibodies that recognize two different epitopes of P
      glycoprotein. Mouse monoclonal antibody HYB-241 detects an extracellular epitope
      of P-glycoprotein, whereas C219 detects a carboxy-terminal intracellular epitope
      and has recently been reported to cross-react with the mdr-3 gene product.
      Differential epitope expression was observed among normal muscle fibers with the
      two antibodies used. Smooth-muscle cells were unreactive for the two antibodies,
      whereas cardiac and a subgroup of skeletal muscle fibers were intensely stained
      by C219, but not by HYB-241. P-glycoprotein expression was observed in 23% of the
      31 myogenic sarcomas analyzed. Our study was conducted mainly using adult
      myogenic sarcomas (28 out of 31 cases), with a few cases (three out of 31 cases)
      of childhood sarcomas. Nineteen tumors were leiomyosarcomas, seven cases were
      embryonal rhabdomyosarcomas, and five cases were rhabdomyosarcomas. We have
      considered expression of the mdr-1-coded P-glycoprotein when we observed either
      HYB-241 and C219 staining, or just HYB-241 immunoreactivities. Although P
      glycoprotein expression can now be detected in human sarcomas, further studies
      are needed, mainly comparing tumor samples before, during, and after therapy, to
      establish the possible significance of the P-glycoprotein expression in clinical
      drug resistance.

PMID- 1384457
TI  - Hemangioendothelioma of the spleen.
AB  - Hemangioendotheliomas of the spleen are rare and are considered to be of
      intermediate/borderline malignancy. We report such a case in a patient who
      presented with chronic anemia but who otherwise was asymptomatic. The tumor
      involved half the organ and was solitary and nonencapsulated. Microscopically, it
      was composed of vascular and stromal elements. Both types of elements showed
      moderate atypia and rare mitoses. The lining cells stained positively with
      antibodies to factor VIII-related antigen and Ulex europaeus lectin. The stromal
      component showed evidence of myofibroblastic differentiation. One year after
      splenectomy, all hematologic parameters slowly improved and returned to normal.
      The clinicopathologic differences between hemangioma, angiosarcoma, and
      hemangioendothelioma are discussed, and cases that have recently been reported in
      the literature are reviewed.

PMID- 1384458
TI  - Aorticopulmonary paraganglioma. A case report with immunohistochemical studies
      and literature review.
AB  - We present a case of nonfunctioning aorticopulmonary paraganglioma in a 41-year
      old man. The mediastinal tumor was accidentally discovered on a chest
      roentgenogram performed for an unrelated minor chest trauma. Complete resection
      of the tumor was done and followed by postoperative radiotherapy. Two years after
      surgery, the patient is well and asymptomatic.

PMID- 1384459
TI  - Intracellular pH changes induced by exposure to weak acids and bases in
      submandibular cells of early postnatal rats.
AB  - The intracellular pH of submandibular cells of adult, 1-day-old and 1-week-old
      rats was measured with the pH sensitive fluorimetric indicator SNARF-1, following
      shifts induced by exposure to a weak acid (sodium butyrate) or a weak base
      (NH4Cl). The effects of several ion transport inhibitors and agonists on both the
      pH change and the rate of recovery were examined. The results indicate that, in
      most respects, the processes involved in pH regulation were similar in the
      neonatal and mature cells. However, cholinergic and peptidergic stimulation
      accelerated recovery from sodium butyrate-induced acidification more, and from
      NH4Cl-induced alkalinization less, in cell preparations from 1-day-old animals.

PMID- 1384460
TI  - Methionine enkephalin-like, substance P-like, and beta-endorphin-like
      immunoreactivity in human parotid saliva.
AB  - These three neuropeptides were measured at daily baseline values by
      radioimmunoassay. Stimulated parotid saliva was collected from 31 subjects using
      a modified Carlson-Crittenden device affixed over Stenson's duct. Methionine
      enkephalin-like immunoreactivity ranged from 6.6 to 11.7 fmol/ml, with a mean of
      9.3 fmol/ml. Substance P-like immunoreactivity ranged from 6.1 to 12.6 fmol/ml,
      with a mean of 9.3 fmol/ml. beta-Endorphin-like immunoreactivity ranged from 1.2
      to 3.6 fmol/ml, with a mean of 2.6 fmol/ml. This is believed to be the first
      documentation of methionine enkephalin- and substance P-like activities in human
      parotid saliva and the first demonstration of beta-endorphin-like activity in any
      type of human saliva. Substance P-like activity was significantly higher in
      morning than evening samples; beta-endorphin-like activity also tended to be
      higher in the morning samples. Substance P and beta-endorphin-like
      immunoreactivities covaried in a significant positive manner, suggesting either
      common control mechanisms or similar responses to physiological variables.

PMID- 1384461
TI  - Systemic antiangiogenic therapy for choroidal neovascularization. What is the
      role of interferon alfa?

PMID- 1384462
TI  - Microrips of the retinal pigment epithelium.
AB  - We describe six patients with exudative age-related macular degeneration who had
      retinal pigment epithelial detachments with associated overlying neurosensory
      detachments. During fluorescein angiography, each patient demonstrated a
      solitary, intense, central serouslike leak at the edge of the retinal pigment
      epithelial detachment with passage of fluorescein into the subretinal space. In
      patients in whom the location of associated choroidal neovascularization was
      evident, the leakage site was remote to the area of neovascularization. Our
      observations suggest that these leaks result from small retinal epithelial rips,
      which we termed "microrips," that differ from conventionally described retinal
      pigment epithelial rips in clinical course and response to laser treatment. We
      hypothesize that the mechanisms and forces that generate these microrips are
      different from those producing conventionally described retinal pigment
      epithelial rips.

PMID- 1384463
TI  - The oxidative pentose phosphate pathway in the heart: regulation, physiological
      significance, and clinical implications.
AB  - The capacity of the oxidative pentose phosphate pathway (PPP) in the heart is
      small, since the activity of glucose-6-phosphate dehydrogenase (G-6-PD), the
      first and rate-limiting enzyme, is very low. Basically, two mechanisms are
      involved in the regulation of this pathway. Under normal conditions, G-6-PD is
      inhibited by NADPH. This can immediately be overcome in the isolated perfused rat
      heart by increasing the oxidized glutathione and by elevating the NADP+/NADPH
      ratio. Apart from this rapid control mechanism, there exists a long-term
      regulation which involves the synthesis of G-6-PD. All catecholamines that were
      administered stimulated the activity of myocardial G-6-PD in a time- and dose
      dependent manner. This stimulation was due to increased new synthesis of enzyme
      protein, since the G-6-PDmRNA was specifically enhanced. As a consequence of the
      stimulation of the oxidative PPP, the available pool of 5-phosphoribosyl-1
      pyrophosphate (PRPP) was elevated which serves as an important precursor
      substrate for purine and pyrimidine nucleotide synthesis. The limiting step in
      the oxidative PPP can be bypassed by ribose which leads to an elevation of the
      cardiac PRPP pool. The decline in the ATP that is induced in many
      pathophysiological conditions can be attenuated or even entirely prevented by
      i.v. infusion of ribose. In some experimental in vivo rat models such as in the
      overloaded and catecholamine-stimulated heart and in the non-ischemic region of
      the infarcted heart, the normalization of the metabolic situation was accompanied
      by an improvement of global heart function. Ribose application has been shown to
      be beneficial in several clinical disease states such as myoadenylate deaminase
      deficiency and McArdle's disease. Moreover, ribose facilitated thallium-201
      redistribution and markedly improved the detection of reversible ischemic injury
      of the pig and human heart.

PMID- 1384464
TI  - Fusion between rat pancreatic zymogen granules and plasma membranes. Modulation
      by a GTP-binding protein.
AB  - At the moment, little is known about the molecular characteristics of the final
      step in the process of regulated exocytosis, i.e. the fusion of the membrane of a
      secretory vesicle with the plasma membrane. We have reconstituted this fusion
      event in vitro, using zymogen granules and plasma membranes from the exocrine
      pancreas of the rat. The membranes of zymogen granules were loaded with the lipid
      soluble fluorescent probe octadecylrhodamine B, at a concentration that resulted
      in self-quenching of its fluorescence. The granules were then incubated with
      pancreatic plasma membranes at 37 degrees C, and fusion was measured through the
      dilution-dependent de-quenching of the fluorescence of the probe. Zymogen
      granules fused with pancreatic plasma membranes, but not with plasma membranes
      from liver or chromaffin cells; granules also fused with unlabelled granule
      membranes. The fusion of granules with plasma membranes was unaffected by
      variation of the Ca2+ concentration over a wide range, but fusion of granules
      with both plasma membranes and zymogen granule membranes was stimulated by GTP
      and, more potently, by guanosine 5'-[gamma-thio]triphosphate (GTP[S]). The effect
      of GTP[S] was to increase the extent of fusion occurring at low concentrations of
      plasma membranes, without affecting the maximum signal obtained at high membrane
      concentrations. Pre-incubation of the plasma membranes with GTP[S] also enhanced
      their ability to fuse with zymogen granules. Our results indicate that membrane
      fusion during exocytosis may be under the direct control of a GTP-binding
      protein.

PMID- 1384465
TI  - Nitric oxide and cyclic GMP formation induced by interleukin 1 beta in islets of
      Langerhans. Evidence for an effector role of nitric oxide in islet dysfunction.
AB  - Treatment of pancreatic islets with interleukin 1 (IL-1) results in a time
      dependent inhibition of glucose-stimulated insulin secretion which has recently
      been demonstrated to be dependent on the metabolism of L-arginine to nitric
      oxide. In this report IL-1 beta is shown to induce the accumulation of cyclic GMP
      (cGMP) in a time-dependent fashion that mimics the time-dependent inhibition of
      insulin secretion by IL-1 beta. The accumulation of cGMP is dependent on nitric
      oxide synthase activity, since NG-monomethyl-L-arginine (a competitive inhibitor
      of nitric oxide synthase) prevents IL-1 beta-induced cGMP accumulation. cGMP
      formation and nitrite production induced by IL-1 beta pretreatment of islets are
      also blocked by the protein synthesis inhibitor, cycloheximide. The formation of
      cGMP does not appear to mediate the inhibitory effects of IL-1 beta on insulin
      secretion since a concentration of cycloheximide (1 microM) that blocks IL-1 beta
      induced inhibition of glucose-stimulated insulin secretion and nitric oxide
      formation does not prevent cGMP accumulation, thus dissociating the two events.
      By using e.p.r. spectroscopy, IL-1 beta is shown to induce the formation of a g =
      2.04 iron-nitrosyl feature in islets which is prevented by cycloheximide,
      demonstrating the requirement of protein synthesis for IL-1 beta-induced nitric
      oxide formation. Iron-nitrosyl complex-formation by islets confirms that IL-1
      beta induces the generation of nitric oxide by islets, and provides evidence
      indicating that nitric oxide mediates destruction of iron-sulphur clusters of
      iron-containing enzymes. Consistent with the destruction of iron-sulphur centres
      is the finding that pretreatment of islets with IL-1 beta results in an approx.
      60% inhibition of mitochondrial oxidation of D-glucose to CO2. Inhibition of
      islet glucose oxidation appears to be mediated by nitric oxide since both NMMA
      and cycloheximide prevent IL-1 beta-induced inhibition of glucose oxidation.
      These results show that IL-1 beta-induced nitric oxide formation parallels the
      ability of IL-1 beta to inhibit glucose-stimulated insulin secretion by islets,
      and that protein synthesis is required for IL-1 beta-induced nitric oxide
      formation. These results also suggest that nitric oxide mediates IL-1 beta
      induced inhibitory effects on the pancreatic beta-cell by functioning as an
      effector molecule responsible for the destruction of iron-sulphur centres of iron
      containing proteins, resulting in an impairment of mitochondrial function.

PMID- 1384466
TI  - The human hepatoma Hep3B cell line as an experimental model in the study of the
      long-term regulation of acute-phase proteins by cytokines.
AB  - The regulation of the synthesis by the cytokines interleukin-1 (IL-1) and IL-6 of
      the positive acute-phase protein alpha 1-acid glycoprotein (AGP) and of the
      negative acute-phase protein alpha 2-HS glycoprotein (AHSG) has been studied in a
      long-term culture system of the human hepatoma cell line Hep3B. The culture
      system contained 30 nM-sodium selenite as the only supplement. This allowed
      maintenance of the synthesis of the proteins under study at a near steady state
      for over 3 months. An increase in AGP mRNA and a decrease in AHSG mRNA were
      observed when cells were treated for two successive 48 h-periods with monocyte
      conditioned medium. A return to basal levels was obtained after cessation of the
      cytokine addition. Two further additions of cytokines led to alterations in mRNA
      levels similar to those observed following the first cytokine treatment. The
      amounts of AGP and AHSG secreted were altered in accordance with the mRNA
      modifications. These results suggest that new cytokine receptors were being
      constantly synthesized during cell culture. When cytokines were present in the
      culture medium for 10 days, maximum alterations in AGP and AHSG synthesis were
      obtained following 2 and 4 days of treatment respectively, but further
      alterations in protein levels could not be observed afterwards. Expression of IL
      6 receptor mRNA was not up-regulated by cytokines, but only by 1 microM
      dexamethasone. Our results show that, in this long-term culture system, cytokines
      induce a response in hepatoma cells similar to that observed in vivo during human
      inflammatory states. This model could be used to evaluate the effects of agonists
      or antagonists of cytokines responsible for the hepatic acute-phase protein
      response.

PMID- 1384467
TI  - Selective activation of p42 mitogen-activated protein (MAP) kinase in murine B
      lymphoma cell lines by membrane immunoglobulin cross-linking. Evidence for
      protein kinase C-independent and -dependent mechanisms of activation.
AB  - Cross-linking of membrane immunoglobulin (mIg), the B lymphocyte antigen
      receptor, with anti-receptor antibodies stimulates tyrosine phosphorylation of a
      number of proteins, including one of 42 kDa. Proteins with a similar molecular
      mass are tyrosine-phosphorylated in response to receptor stimulation in other
      cell types and have been identified as serine/threonine kinases, termed mitogen
      activated protein (MAP) kinases or extracellular signal-regulated kinases (ERKs).
      The MAP kinases constitute a family of related kinases, at least three of which
      have molecular masses of 40-45 kDa. In this paper we show that mIg cross-linking
      stimulated the myelin basic protein phosphotransferase activity characteristic of
      MAP kinase in both mature and immature murine B cell lines. This enzyme activity
      co-purified on three different columns with a 42 kDa protein that was tyrosine
      phosphorylated (pp42) in response to mIg cross-linking and which reacted with a
      panel of anti-(MAP kinase) antibodies. Although immunoblotting with the anti-(MAP
      kinase) antibodies showed that these B cell lines expressed both 42 kDa and 44
      kDa forms of MAP kinase, only the 42 kDa form was activated and tyrosine
      phosphorylated to a significant extent. Activation of protein kinase C (PKC) with
      phorbol esters also resulted in selective tyrosine phosphorylation and activation
      of the 42 kDa MAP kinase. This suggested that mIg-induced MAP kinase activation
      could be due to stimulation of PKC by mIg. However, mIg-stimulated MAP kinase
      activation and pp42 tyrosine phosphorylation was only partially blocked by a PKC
      inhibitor, the staurosporine analogue Compound 3. In contrast, Compound 3
      completely blocked the ability of phorbol esters to stimulate MAP kinase activity
      and induce tyrosine phosphorylation of pp42. Thus mIg may activate MAP kinase by
      both PKC-dependent and -independent mechanisms.

PMID- 1384469
TI  - Polyclonal antibody against an inducible form of nitric oxide synthase purified
      from the liver of rats treated with Propionibacterium acnes and
      lipopolysaccharide.
AB  - A polyclonal antibody was raised in the rabbit against an inducible form of
      nitric oxide (NO) synthase (EC 1.14.23) purified from the liver of rats with
      acute liver necrosis induced by i.v. administration of Propionibacterium acnes
      and lipopolysaccharide. The antibody immunoprecipitated NO synthase activities in
      the soluble extract of the liver from treated rats. Western blot analysis showed
      that the cytosols of the liver, lung and spleen from the treated rats but not
      from non-treated rats, and that of murine macrophages cultured in the presence of
      lipopolysaccharide and interferon-gamma, contained immunoreactive protein with a
      molecular weight of 125 kDa. The antibody, however, does not cross-react with a
      150 kDa constitutive form of NO synthase present in the brain of rats, indicating
      that the inducible and constitutive enzymes are immunologically distinguishable.

PMID- 1384468
TI  - Phosphatidylcholine-specific phospholipase D-derived 1,2-diacylglycerol does not
      initiate protein kinase C activation in the RBL 2H3 mast-cell line.
AB  - We examined the role of phosphatidylcholine-specific phospholipase D (PC-PLD) in
      the IgE-dependent activation of protein kinase C (PKC) in RBL 2H3 cells (a model
      for mast-cell function). Cells were sensitized with mouse monoclonal anti
      trinitrophenol (TNP) IgE (0.5 micrograms/ml) and were then triggered with an
      optimal concentration (10 ng/ml) of TNP-ovalbumin conjugate (TNP-OVA). This
      resulted in an immediate biphasic increase in the production of 1,2
      diacylglycerol (DAG) and activation of PKC. The initial increase in DAG
      production reached a peak within 30 s, and the second phase reached a plateau
      within 5 min after stimulation. TNP-OVA-induced PC-PLD activation followed the
      initial increase in DAG formation in response to IgE-receptor cross-bridging, but
      coincided with the second peak. Phosphatidic acid (PA), derived from the PC-PLD
      pathway, is metabolized to DAG by the action of PA phosphohydrolase (PAPase).
      Propranolol (0.3 mM), which inhibits PAPase, blocked the IgE-dependent increase
      in DAG, activation of PKC, and subsequently degranulation. The PKC inhibitor
      staurosporine (0.1 microM) inhibited the second, but not first, peak of DAG
      accumulation, reversed PKC translocation after 10 min and inhibited subsequent
      mediator release. Taken together, these results demonstrate that PC-PLD does not
      initiate, but may play a latent role in, IgE-dependent DAG production, PKC
      activation and mediator release from RBL 2H3 cells.

PMID- 1384470
TI  - Rabbit FKBP59-heat shock protein binding immunophillin (HBI) is a calmodulin
      binding protein.
AB  - FKBP59-HBI, a heat shock protein hsp90-binding immunophilin that was originally
      detected in heterooligomer forms of steroid receptors, is retained on Calmodulin
      (CAM)-Sepharose 4B in the presence of 2 mM Ca2+ and is eluted by EGTA,
      demonstrating a specific p59-CAM interaction. The p59 amino acid sequence reveals
      the presence of two putative CAM binding sites in a helix regions of the protein,
      as well as PEST sequences which are generally present in CAM-binding proteins. In
      vitro proteolysis by calpain II (a Ca(2+)-activated neutral protease), another
      feature of CAM-binding proteins, generates shorter peptides revealed by the mAb
      EC1, but not by the pAb 173 which recognizes the C-terminal of the protein. The
      potential function of CAM binding by the hsp90-binding immunophilin is discussed.

PMID- 1384471
TI  - In vitro synthesis of bacterio-opsin: integration into microsomal membranes.
AB  - The translation and membrane integration of bacterio-opsin from Halobacterium
      salinarium were investigated. Plasmids containing the bacterio-opsin-gene with or
      without its original presequence were transcribed with the T7-RNA-polymerase and
      translated in vitro in a wheat germ system. The integration of the expressed
      bacterio-opsin into dog pancreas microsomes was studied. Both precursor bacterio
      opsin and mature bacterio-opsin integrate into the eukaryotic membrane.

PMID- 1384473
TI  - RNA hydrolysis via an oxyphosphorane intermediate.
AB  - From calculations of a model reaction scheme for base-catalyzed RNA hydrolysis, a
      pentacoodinate dianionic intermediate 2a (Storer, et al., J. Am. Chem. Soc.,
      1991, 113, 5216-5219) as well as two transition states, TS1 and TS2, to the
      intermediate have been located by ab initio calculations at the 3-21G* level.
      Although the intermediate, which has the well depth on the order of kBT, is
      unlikely to be kinetically significant, the overall rate-limiting transition
      state structure TS2 obtained at 3-21G* level is very close to the corresponding
      structure at the STO-3G level; it has an extended P-O(5') bond breaking
      character. These gas-phase calculation results are used to qualitatively
      interpret mutagenesis results of Barnase and RNase T1 where water molecules are
      absent from the active site.

PMID- 1384472
TI  - 1,10-Phenanthroline-copper, a footprinting reagent for single-stranded regions of
      RNAs.
AB  - The 1,10-phenanthroline-cuprous complex (OP-Cu) with hydrogen peroxide as a
      coreactant nicks the single-stranded loops and bulges of RNA stem-loop structures
      more rapidly than the double-stranded stems. This chemical nuclease is therefore
      a useful footprinting reagent for these regions and can be used to monitor both
      intramolecular and intermolecular hybridization of single-stranded domains. The
      formation of A-form structures characteristic of either RNA-RNA or RNA-DNA
      duplexes inhibits scission because it blocks the binding site of the coordination
      complex in single-stranded loops and not because the oxidatively sensitive
      hydrogens of the ribose moiety are blocked. The C-4' and C-1' hydrogens are
      accessible to solvent in A-structures.

PMID- 1384474
TI  - Cross-linking of surface immunoglobulin activates src-related tyrosine kinases in
      WEHI 231 cells.
AB  - Crosslinking of sIgM on the B cell line WEHI 231 with anti-sIgM antibody induces
      protein tyrosine phosphorylation, implicating protein tyrosine kinases (PTKs) in
      sIg-mediated signal transduction. We have analyzed this cell line for members of
      the src family of PTKs and have evaluated whether these PTKs might be involved in
      the process of sIgM-mediated signaling. Our results show that Blk, Lyn, Lck, and
      Hck are detectable in WEHI 231 cells. Addition of antibodies to sIgM were found
      to variably stimulate the activities of Blk, Lyn, Lck, and Hck as measured by
      immune-complex protein kinase assays. Autophosphorylation of these src PTKs, as
      assessed by reaction with anti-phosphotyrosine antibodies, increased over the
      time course of sIgM-mediated activation. Co-immunoprecipitation studies to
      investigate the potential physical interaction of src PTKs with the sIgM receptor
      complex revealed that, under digitonin and Brij 96 lysis conditions Lyn, Lck,
      Hck, but not Blk associated with sIgM.

PMID- 1384475
TI  - Detection of endothelin-1 mRNA by RT-PCR in isolated rat renal tubules.
AB  - A combination of reverse transcription and polymerase chain reaction was utilized
      to detect baseline endothelin-1 (ET-1) mRNA expressed in renal tubules dissected
      from rats. 5' and 3' primers were constructed according to human ET-1 genomic
      DNA. Rat ET-1 mRNA was found to be expressed only in cortical through medullary
      collecting ducts in addition to glomeruli. Sites for tubular synthesis of ET-1
      corroborate well with major ET-1 binding sites along the nephron, indicating
      autocrine/paracrine role of ET-1 in the renal tubules and supporting a prevailing
      concept on such function of ET-1 in many differing tissues.

PMID- 1384477
TI  - Analysis of antibody response to ovine lentivirus by using viral gene products
      expressed in a prokaryotic system.
AB  - The polymerase chain reaction (PCR) was used to amplify, clone, and express eight
      DNA fragments encoding p25, p16, reverse transcriptase (RT) core, C'-terminal RT,
      N'- and C'-terminals of external (gp70), and transmembrane (gp40) envelope
      proteins from visna virus infectious recombinant DNA. Efforts were focused on
      characterizing the nature of the humoral immune response of ovine progressive
      pneumonia (OPP) virus infected animals and identifying the conserved and prime
      reactive antigenic determinants that have potential diagnostic value. This
      communication reports that the N'-terminal region of gp40 appeared to be the most
      immunoreactive of the bacterially expressed proteins and could serve as a
      sensitive immunodiagnostic antigen for the detection of OPP infection.

PMID- 1384476
TI  - A serine-->proline change in the Alzheimer's disease-associated epitope Tau 2
      results in altered secondary structure, but phosphorylation overcomes the
      conformational gap.
AB  - Monoclonal antibody Tau 2 was raised against bovine tau protein, was reported to
      recognize a conformational epitope, and stained tau was found in neurofibrillary
      tangles of Alzheimer's disease, but not normal human tau. We synthesized
      tetradeka peptides corresponding to the original bovine sequence, its serine-
      >proline substituted analog, the genuine human sequence of this region, and the
      bovine epitope phosphorylated on the crucial serine. The secondary structure of
      the peptides was determined by circular dichroism. It was found that only the
      original bovine epitope showed a tendency to form the beta-pleated sheets
      characteristic of the neurofibrillary tangles. The spectra of the human peptide,
      its analog, and the phosphorylated bovine sequence were very similar, featuring a
      weak, helical beta-turn character. Eventual phosphorylation of epitopes of this
      otherwise heavily phosphorylated protein may overcome inter-species
      conformational gaps.

PMID- 1384478
TI  - Glucocorticoids do not affect the induction of a novel calcium-dependent nitric
      oxide synthase in rabbit chondrocytes.
AB  - Incubation of rabbit articular chondrocytes with interleukin-1 beta caused time
      dependent expression of NO synthase, determined as nitrite, after a lag period of
      6h. The synthesis of nitrite was concentration-dependent and was inhibited by
      cycloheximide and NG-monomethyl-L-arginine, but not by dexamethasone or
      hydrocortisone. The synthesis of NO in the 100,000g supernatant of activated
      chondrocytes was inhibited by EGTA, but not by the calmodulin inhibitors W-13 or
      trifluoperazine. The synthesis of NO was half-maximal at approximately 20nM free
      Ca2+. Endotoxin also induced the expression of this NO synthase. Thus, rabbit
      articular chondrocytes express a novel inducible NO synthase which is Ca(2+)
      dependent, and whose induction is not prevented by glucocorticoids.

PMID- 1384479
TI  - Up-regulation of hepatocyte growth factor gene expression by interleukin-1 in
      human skin fibroblasts.
AB  - Hepatocyte growth factor (HGF) functions as a hepatotrophic and renotrophic
      factor for regeneration of the liver and kidney. When 1 ng/ml of interleukin-1
      alpha (IL-1 alpha) or interleukin-1 beta (IL-1 beta) was added to cultures of
      human skin fibroblasts, the production of HGF was 5-6 fold higher than levels in
      the controls. HGF mRNA level in the cells was increased to 4-fold higher levels
      at 6 h after exposure to IL-1 alpha. Tumor necrosis factor-alpha and interferon
      gamma but no other cytokine tested had slightly stimulatory effects on HGF
      production. The tumor promoter, tetradecanoylphorbol 13-acetate (TPA) markedly
      enhanced the stimulatory effect of IL-1 alpha and IL-1 beta on the production of
      HGF. The stimulatory effect of both IL-1 alpha and IL-1 beta and the
      synergistical stimulation with TPA were completely abrogated by 10 ng/ml TGF-beta
      1 or 1 microM dexamethasone. These results suggest that IL-1 alpha and IL-1 beta
      are positive regulators for expression of the HGF gene and are likely have a role
      in regeneration of tissues following the occurrence of inflammatory diseases.

PMID- 1384480
TI  - High affinity binding of the leucocyte adhesion molecule L-selectin to 3'
      sulphated-Le(a) and -Le(x) oligosaccharides and the predominance of sulphate in
      this interaction demonstrated by binding studies with a series of lipid-linked
      oligosaccharides.
AB  - The binding of the leucocyte adhesion molecule L-selectin has been investigated
      toward several structurally defined lipid-linked oligosaccharides immobilized on
      silica gel chromatograms or plastic wells. In both assay systems the 3'-sulphated
      Le(a)/Le(x) type tetrasaccharides [formula: see text] were more strongly bound
      than 3'-sialyl analogues. A considerable binding was observed to the 3'-sulphated
      oligosaccharide backbone in the absence of fucose but not to a 3'-sialyl analogue
      or fuco-oligosaccharide analogues lacking sulphate or sialic acid. Affinity for
      other sulphated saccharides: 3'-sulphoglucuronyl neolactotetraosyl ceramide and
      glycolipids with sulphate 3'-linked to terminal or sub-terminal galactose or N
      acetylgalactosamine was detected in the chromatogram assay only. These studies,
      together with earlier reports that L-selectin binding to endothelium is inhibited
      by sulphatide, highlight the relative importance of sulphate in the adhesive
      specificity of this protein.

PMID- 1384481
TI  - Dityrosine formation is impaired by tyrosine phosphorylation.
AB  - Using pure tyrosine and phosphotyrosine we have recently shown that
      phosphotyrosine is unable to form peroxidase catalyzed dimers (1989, FEBS Lett.
      255, 395-397). In the present report, the effect of phosphotyrosine residues
      within a protein structure on dityrosine formation was studied using casein as a
      model protein. Dephosphorylation of casein resulted in a dose and time dependent
      increased synthesis of dityrosines following treatment with peroxidase/H2O2. The
      extent of crosslink formation was inversely related to the amount of
      phosphorylated tyrosine residues as quantitated by immunoblotting. Thus,
      phosphorylation of tyrosine residues could play a regulatory role in protein
      crosslinking where dityrosine bonds are involved.

PMID- 1384482
TI  - Angiotensin II stimulates the pp44 and pp42 mitogen-activated protein kinases in
      cultured rat aortic smooth muscle cells.
AB  - Vasoconstrictors such as angiotensin II (ang II) stimulate vascular smooth muscle
      cell growth and share many signal transduction mechanisms with growth factors.
      Recently, growth factors have been shown to stimulate mitogen-activated protein
      (MAP) kinases, a family of serine/threonine protein kinases which phosphorylate
      pp90rsk, a cytosolic kinase that phosphorylates ribosomal S6 protein. We examined
      the effect of ang II on MAP kinase activity and phosphorylation. Ang II
      stimulated MAP kinase activity by 4-fold after 5 min exposure and also increased
      tyrosine phosphorylation of 42 kDa (74 +/- 41%) and 44 kDa (263 +/- 85%)
      proteins, shown to be pp42mapk and pp44mapk by Western blot analysis using a MAP
      kinase antibody. These results suggest that ang II-stimulated protein synthesis
      is mediated by a MAP kinase dependent pathway.

PMID- 1384483
TI  - Graves' IgG recognizes linear epitopes in the human thyrotropin receptor.
AB  - Twenty-nine peptides covering the full extracellular domain of the human
      thyrotropin receptor have been synthesized and tested for reactivity with Graves'
      patients' and normal sera in ELISA. Two peptides, amino acids 331-350 and the
      second extracellular loop of the transmembrane segment, bound IgG-s from 5 and 4
      of 10 Graves' disease patients' sera, respectively. Neither of these two peptides
      showed enhanced binding to normal IgG. There were no apparent differences between
      the Graves' disease and normal group with respect to the other 27 peptides. We
      conclude that peptide 331-350 and the second extracellular loop carry important
      linear epitopes which may contribute to the disease process in selected Graves'
      patients.

PMID- 1384484
TI  - Deletion mutagenesis of stem cell factor defines the C-terminal sequences
      essential for its biological activity.
AB  - We constructed a series of murine stem cell factor (mSCF) cDNAs which were
      sequentially truncated at the 3' termini. The resultant six mutant cDNA encode N
      terminal 183, 179, 162, 149, 142 and 133 amino acid residues of the mature mSCF
      protein fused to the heterogeneous C-terminal peptides derived from the linker
      sequences. Each mutant cDNA was transiently expressed in COS cells, and the
      cultured supernatant was assayed for its ability to support the growth of a human
      factor-dependent cell line, TF-1 and to enhance colony formation by murine
      hematopoietic progenitor cells. The results showed that as few as N-terminal 142
      but not 133 amino acid residues of mSCF remained biologically active in vitro,
      suggesting that the region of 9 amino acids from Asp134 to Ser142 containing a
      Cys138-mediated disulfide bond may contribute to the C-terminal end of the active
      subdomain of mSCF.

PMID- 1384485
TI  - Molecular cloning of the acid-labile subunit of the rat insulin-like growth
      factor binding protein complex.
AB  - The insulin-like growth factors, IGF-I and IGF-II, circulate in both humans and
      rats as part of a 125-150 kDa complex comprising IGFs, the IGF binding protein
      IGFBP-3, and an acid-labile subunit. Clones encoding rat acid-labile subunit have
      been isolated from a rat liver cDNA library probed with a human acid-labile
      subunit cDNA. Two overlapping clones encode a leucine-rich protein of 576 amino
      acids preceded by a 27-residue signal sequence, with 78% homology to the human
      acid-labile subunit. Northern analysis of mRNA from adult rat brain, kidney,
      heart, lung, spleen, muscle and liver shows a major species of about 4.4 kb and
      minor bands of about 2 kb, 1.4 kb and 1 kb. The tissue distribution of this
      protein may therefore be wider than previously recognized.

PMID- 1384486
TI  - Interleukin-2 (IL-2) induces erythroid differentiation and tyrosine
      phosphorylation in ELM-I-1 cells transfected with a human IL-2 receptor beta
      chain cDNA.
AB  - The molecular mechanism of erythroid differentiation has been still ill-defined.
      In this study, we introduced a human interleukin-2 receptor (IL-2R) beta chain
      cDNA into ELM-I-1 cells which differentiated into hemoglobin-positive cells in
      the presence of erythropoietin (Epo), and established the transformant which
      expressed IL-2R beta chain. In this transformant, we revealed that IL-2 induced
      erythroid differentiation and the same pattern of tyrosine phosphorylation as
      Epo. These data suggest that tyrosine phosphorylation is involved in signal
      transduction pathway of erythroid differentiation. It is also implicated that the
      Epo and IL-2 receptor system share a common signal transduction pathway.

PMID- 1384487
TI  - Interferon-gamma inhibits proliferation of rat vascular smooth muscle cells by
      nitric oxide generation.
AB  - Interferon (IFN)-gamma inhibited the proliferation of rat vascular smooth muscle
      cells (VSMC) and increased the cyclic GMP (cGMP) concentration in the cells. The
      dose dependencies of the two effects were similar (IC50 = 4 U/ml for the anti
      proliferation and EC50 = 3 U/ml for cGMP formation) and the effect of IFN-gamma
      was enhanced by tumor necrosis factor-alpha treatment. Furthermore, NG-nitro-L
      arginine, a nitric oxide (NO) synthase inhibitor, inhibited both activities
      induced by IFN-gamma. These findings show that the anti-proliferation and cGMP
      formation are closely related and that IFN-gamma inhibits the proliferation of
      rat VSMC by generation of NO through the induction of an NO synthase.

PMID- 1384488
TI  - Differential gene expression and regulation of type-1 angiotensin II receptor
      subtypes in the rat.
AB  - A simplified and sensitive method for measuring expression levels of type-1
      angiotensin II (AT1) receptor subtypes, AT1A and AT1B, was established. The two
      receptor cDNAs were co-amplified and measured by polymerase chain reaction using
      primers based on the corresponding receptor subtype genes. Both AT1A and AT1B
      mRNAs were widely expressed in the rat tissues including adrenal gland, kidney,
      heart, aorta, lung, liver, testis, pituitary gland, cerebrum and cerebellum. AT1A
      mRNA was predominantly expressed in the rat tissues examined except adrenal gland
      and pituitary gland where AT1B mRNA was predominantly expressed. Sodium depletion
      did not change mRNA levels of AT1A and AT1B in the all tissues. However, both
      AT1A and AT1B mRNA levels in the heart and aorta were down-regulated by treatment
      with AT1 specific antagonist, TCV 116. In contrast, AT1B mRNA in the adrenal
      gland was mainly reduced by the treatment. These results suggest that the
      expression level of AT1B mRNA in the adrenal gland depends on the activity of the
      renin-angiotensin-aldosterone system (RAAS) and both receptor subtypes mediate
      contraction and hypertrophy of the smooth and cardiac muscles via the RAAS.

PMID- 1384489
TI  - Regulation of manganese superoxide dismutase: IL-1 and TNF induction in pulmonary
      artery and microvascular endothelial cells.
AB  - IL-1 and TNF are important mediators in the inflammatory response, and have been
      associated with endothelial cell damage in the lung. TNF and IL-1 cell-mediated
      injury has been proposed to occur through an increase in intracellular oxygen
      free radical production. However, these cytokines have also been shown to protect
      the lung from hyperoxia-mediated oxidant injury. In this paper we evaluated the
      response of the antioxidant enzymes, MnSOD and Cu/ZnSOD to IL-1, TNF, and LPS in
      both rat pulmonary artery and microvascular endothelial cells. These mediators
      produced an increase in MnSOD but not Cu/ZnSOD expression in both rat pulmonary
      endothelial cells. An additive effect was observed with co-treatment by the
      cytokines with LPS. The MnSOD mRNA induction is dependent upon a transcriptional
      event, but did not require de novo protein synthesis.

PMID- 1384491
TI  - Roles of the aromatic residues in cobrotoxin in antigenicity and binding activity
      to nicotinic acetylcholine receptor.
AB  - The single Trp-29 in cobrotoxin was modified with 2-hydroxy-5-nitrobenzyl
      bromide, and Tyr-25 and -35, with tetranitromethane. Although the binding
      activity of cobrotoxin to the nicotinic acetylcholine receptor (nAChR) was
      decreased after modification of Trp-29, the antigenicity remained essentially
      unchanged as measured by a competitive RIA. Tyr-35-nitrated cobrotoxin still
      retained relatively high antigenicity and potent binding activity to nAChR.
      However, modification of both Tyr-25 and Tyr-35 led to an altered secondary
      structure, with greatly reduced binding to antibody and receptor. Hence, Tyr-25
      in cobrotoxin is essential for the maintenance of the active conformation for the
      bindings. Although the non-precipitating antibody against cobrotoxin exhibiting a
      higher neutralizing capacity than did the precipitating antibody, the binding
      affinity of the former to cobrotoxin and its modified derivatives was lower than
      that of the latter.

PMID- 1384490
TI  - Gamma-interferon counteracts interleukin-1 alpha stimulated expression of
      urokinase-type plasminogen activator in human endothelial cells in vitro.
AB  - The effect of gamma-interferon (gamma-IFN) on the interleukin-1 alpha (IL-1
      alpha) induced stimulation of urokinase-type plasminogen activator (u-PA)
      expression in human foreskin microvascular endothelial cells (HFMEC) and in human
      umbilical vein endothelial cells (HUVEC) was investigated. When gamma-IFN and IL
      1 alpha were added to the cells simultaneously, gamma-IFN inhibited the IL-1
      alpha induced increase in u-PA antigen production in both HFMEC and HUVEC in a
      dose dependent fashion, with a maximum inhibitory effect achieved between 2.0 and
      20.0 U/ml of gamma-IFN. Pretreatment of HFMEC with gamma-IFN for 1 hour before
      addition of IL-1 alpha resulted in a significant reduction in u-PA synthesis.
      However, when HFMEC were pretreated for 8 hours with gamma-IFN before the
      addition of IL-1 alpha the reduction in u-PA production was even more
      significant. When gamma-IFN was added to HFMEC 1 hour after IL-1 alpha, a
      significant inhibition in u-PA synthesis was seen. In contrast only a slight
      inhibition in IL-1 alpha induced u-PA production was seen when gamma-IFN was
      added to the cells 8 hours after IL-1 alpha. gamma-IFN also inhibited
      significantly the IL-1 alpha induced increase in u-PA specific mRNA in HUVEC and
      HFMEC.

PMID- 1384492
TI  - Platelet-agglutinating protein p37 from a thrombotic thrombocytopenic purpura
      plasma forms complexes with platelet membrane glycoprotein IV (CD36).
AB  - We have previously reported the purification of a 37 kDa platelet agglutinating
      protein (PAPp37) from the plasma of a patient with Thrombotic Thrombocytopenic
      purpura (TTP), and have shown recently that p37 causes platelet agglutination
      through its binding to membrane glycoprotein IV (GPIV). To gain further insight
      into the mechanism of p37 binding to GPIV, we have studied the interaction
      between p37 and GPIV. We now demonstrate specific complex formation of p37 with
      GPIV. In Western immunoblotting p37 binds to purified GPIV and the complex formed
      between the two proteins was detected by polyclonal antibody to p37 and
      peroxidase conjugated second antibody. No binding of p37 was noticed with the
      purified GPIIIa. A solid phase binding assay was developed to study the complex
      formation. Microtiter wells were coated with GPIV and the control proteins; 125I
      p37 was added, allowed to bind and bound radioactivity was measured. Several
      lines of evidence indicate that the binding of p37 to GPIV was specific. a) GPIV
      immobilized on Immulon-2 wells bound 10-30 fold more p37 than immobilized
      fibrinogen, GPIIIa, and BSA. b) Polyclonal antibodies against p37 and GPIV
      inhibited the binding by 39-68% as compared with control IgG. c) GPIIIa antibody
      did not inhibit the binding. Molecular sieve chromatography of a mixture of 125I
      p37 and GPIV also revealed the fluid phase complex formation ranging in molecular
      weight from 132,000 to over 350,000 daltons. These results show the specific
      interaction between p37 and GPIV and suggest that GPIV functions as a p37
      receptor during platelet agglutination.

PMID- 1384493
TI  - Lack of effect of hypothyroidism on rat liver regeneration.
AB  - Thyroid hormone has been postulated to be important for liver regeneration. In
      the present studies liver regeneration in hypothyroid male rats treated with
      methimazole was compared to euthyroid rats. At 5 days after 70% partial
      hepatectomy liver weight was significantly less in the hypothyroid rats, but
      total hepatic DNA and protein were the same in the hypothyroid and euthyroid rats
      and RNA was significantly greater in the hypothyroid rats. These results indicate
      that liver regeneration is nearly normal in hypothyroid rats, despite the fact
      that whole body growth has ceased due to the hypothyroidism. Since both thyroid
      and growth hormones are low in hypothyroid rats, these results suggest that
      neither thyroid nor growth hormones are required for liver regeneration.

PMID- 1384494
TI  - Influence of immunogen modification of the gonadotropin releasing hormone
      antibody reactivity.
AB  - The binding of MoAbs and PoAbs to native GnRH, azo-GnRH, GnRH-BSA and azo-GnRH
      BSA conjugates was studied using a solid phase ELISA test. The use of
      carbonate/bicarbonate buffer (pH 9.2) significantly affected the coating of
      peptide to the ELISA plates. Azo-GnRH coated in PBS showed seven times less
      binding to MoAb than the native GnRH. Saturation analysis studies indicated
      comparable binding to the antibodies to the coated GnRH and GnRH-BSA but binding
      to azo-GnRH-BSA was higher than to azo-GnRH. The epitope recognition ability of
      MoAbs was therefore investigated. Blocking ELISA additivity tests were performed
      to analyse whether MoAbs recognised a common epitope involving a conformation or
      sequence of the modified peptide (azo-GnRH). The plates coated with azo-GnRH or
      azo-GnRH-BSA and saturated with MoAbs did not bind PoAbs. The inhibition activity
      was similar when GnRH or GnRH-BSA was used instead of azo-GnRH or azo-GnRH-BSA
      thus suggesting that the MoAbs were directed against a conformational epitope of
      the GnRH molecule.

PMID- 1384495
TI  - Peptide fragments of myelin basic protein as substrates of protein kinase C.
AB  - A set of peptides derived from myelin basic protein was synthesized and the
      kinetics of their phosphorylation by protein kinase C was studied. The
      replacement or the removal of the N-terminal Gln had no effect on the activity of
      the parent peptide. The removal of the following Lys or Arg led to a systematic
      decrease in substrate activity. The modifications in the C-terminal part of the
      peptide had a weaker influence on the parameters Vmax and KM than those in the N
      terminal. The rather regular dependence of the activity of substrates upon their
      structure does not allow the strict definition of a minimum substrate for protein
      kinase C.

PMID- 1384496
TI  - Senescent human fibroblasts are more sensitive to the effects of a phorbol ester
      on macromolecular synthesis and growth characteristics.
AB  - 4-beta-phorbol-12-beta-myristate-13-alpha-acetate (PMA) alters cellular growth
      properties by modulating gene expression in a wide variety of cell types. Human
      diploid fibroblasts MRC-5 were treated with PMA at different phases of their
      lifespan in vitro and the alterations of their short-term growth characteristics
      and macromolecular synthesis in response to PMA were analysed. PMA stimulates DNA
      and RNA synthesis in both Phase II (young) and Phase III (senescent) MRC-5 cells.
      Treatment of senescent cells with various PMA concentrations results in a greater
      stimulation of DNA and RNA synthesis than that in young cells. Senescent cells
      are also more sensitive to the PMA-induced alterations of growth characteristics
      and higher concentrations of PMA become toxic for them. The age-related
      alterations of cellular responsiveness are also apparent in the gradual loss of
      responsiveness to serum, observed in parallel with the increased sensitivity to
      PMA. Furthermore, serum-induced stimulation of macromolecular synthesis is
      inhibited by PMA. Since it is known that serum and PMA elicit their effects via
      different signal transduction pathways, our results point to suggest the
      differential regulation of the signalling mechanisms during cellular ageing.

PMID- 1384497
TI  - Neutrophil priming by granulocyte colony stimulating factor and its modulation by
      protein kinase inhibitors.
AB  - Upon stimulation by various ligands, freshly isolated human peripheral
      neutrophils (PMN) respond in a variety of ways, such as superoxide (O2-.)
      generation, phagocytosis enzyme release, migration etc. Chemotactic peptide
      formylmethionyl-leucyl-phenylalanine (FMLP) and opsonized zymosan activate
      neutrophils by a receptor-mediated mechanism, while phorbol myristate acetate and
      dioctanoylglycerol activate the cells by a mechanism involving Ca(2+)-and
      phospholipid-dependent protein kinase (PKC). Receptor-mediated but not PKC
      mediated O2-. generation in PMN was enhanced by the priming of recombinant human
      granulocyte colony stimulating factor (G-CSF). FMLP-dependent luminol
      chemiluminescence was also enhanced by G-CSF. However, no appreciable enhancement
      was observed in FMLP-induced intracellular calcium ion concentration ([Ca2+]i).
      Enhancement of FMLP-induced generation of O2-. by G-CSF was inhibited by
      genistein or alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide (ST
      638), inhibitors of tyrosine kinase (TK), and was stimulated by staurosporine and
      1-(5-isoquinolinesulfonyl)-3-methyl-piperazine (H-7), inhibitors of PKC. The ED50
      values of genistein and ST 638 for the inhibition of the FMLP-induced O2-.
      generation from G-CSF were 0.5 and 5 microM, respectively. In contrast, O2-.
      generation by PKC activation without G-CSF priming was inhibited by stauroporine
      and H-7, but was stimulated by genistein and ST 638. These results suggested that
      the enhancing effect of G-CSF on receptor-mediated generation of the O2-. might
      be regulated by protein kinases, such as TK and PKC, and that the TK inhibitor
      selectively inhibited the G-CSF-primed receptor-mediated O2-. generation of
      neutrophils.

PMID- 1384498
TI  - Bleomycin-induced unscheduled DNA synthesis in non-permeabilized human and rat
      hepatocytes is not paralleled by 8-oxo-7,8-dihydrodeoxyguanosine formation.
AB  - The genetic toxicity of the antitumour antibiotic bleomycin (BLM) is thought to
      involve the formation of a reactive oxygen intermediate. 8-Oxo-7,8
      dihydrodeoxyguanosine (oxo8dG), an oxidation product of deoxyguanosine, is one of
      the major products formed when isolated DNA is exposed to oxygen radical
      generating systems. Gamma-irradiation (10-500 Gy 60Co; 10 Gy/min) or BLM and Fe2+
      (37.5-150 U/L and 0.5 mM, respectively) treatment of isolated DNA (0.25 mg/mL)
      increased oxo8dG above background. In the latter case, the effect was greater
      than that with Fe2+ (0.5 mM) alone and was dependent on the dose of BLM. When DNA
      was irradiated with 500 Gy60Co, deoxyguanosine oxidation was inhibited by
      antioxidants (ethanol: 37.5 and 98% inhibition at 2 and 20 mM, respectively;
      mannitol: 20.5, 60 and 92% inhibition at 0.1, 1.0 and 10 mM, respectively).
      Similarly the BLM-induced production of oxo8dG was inhibited (64%) by mannitol
      (10 mM). BLM also caused production of base propenals on interaction with
      isolated DNA. In contrast, oxo8dG was not induced above background concentration
      (27 mol oxo8dG/10(6) mol dG) in permeabilized (37 degrees) and non-permeabilized
      (4 degrees and 37 degrees) rat hepatocytes treated with BLM (260 U/L). Despite
      this, there was extensive BLM-induced unscheduled DNA synthesis (10 and 100 U/L)
      in non-permeabilized rat and human hepatocytes in the absence of hydroxyurea.
      These findings, in accord with other observations, draw into question the role of
      .OH in BLM-induced DNA damage and the mimicry of ionizing radiation in cellular
      systems.

PMID- 1384499
TI  - Effects of flavonoids on cyclic AMP phosphodiesterase and lipid mobilization in
      rat adipocytes.
AB  - Thirty-one flavonoids were tested for their effects on low Km phosphodiesterase
      with cyclic AMP as the substrate. Quercetin, luteolin, scutellarein, phloretin
      and genistein showed inhibitory potencies comparable to or greater than 3
      isobutyl-2-methylxanthine (EC50 30-50 microM). Only four compounds namely,
      catechin, epicatechin, taxifolin and fustin stimulated the enzyme activity
      (stimulatory EC50 130-240 microM). The most potent phosphodiesterase (PDE)
      inhibitors were aglycones that had a C2.3 double bond, a keto group at C4 and
      hydroxyls at C3' and/or C4'. However, when the C-ring is opened then the
      requirement for the C2.3 double bond is eliminated. The same series of flavonoids
      were also tested for their lipolytic activity. The structural features required
      for effective synergistic lipolysis (with epinephrine) were generally similar to
      that required for potent PDE inhibition except that, for lipolytic activity, an
      intact C-ring was necessary. Fisetin and quercetin having the above-mentioned
      structure showed a dose- and time-dependent increase in lipolysis which was
      synergistic with epinephrine. Only butein and hesperetin showed inhibition of
      epinephrine-induced lipolysis, and their effect was dose-dependent. A time-course
      study indicated that hesperetin was able to delay the lipolytic action of
      epinephrine. It is most likely that the lipolytic effects of these compounds were
      not a result of PDE inhibition, as the orders of potency for the two activities
      had poor correlation. Apparently, the effective lipolytic flavonoids were also
      potent PDE inhibitors but not all the PDE inhibitors were able to induce
      lipolysis.

PMID- 1384500
TI  - de novo synthesis of calmodulin binding protein in substance P-induced
      steroidogenesis in bovine adrenocortical cells.
AB  - In order to clarify the mechanism of substance P (SP)-induced cortisol secretion
      from bovine adrenocortical (BAC) cells, protein synthesis at the early stage of
      SP-stimulation in BAC cells was investigated. Both SP and adrenocorticotropic
      hormone (ACTH) increased [3H]leucine uptake into BAC cells in a dose-dependent
      fashion. Although the SP-induced [3H]leucine uptake precedes the cortisol
      secretion, ACTH was slower in inducing [3H]leucine uptake and cortisol secretion.
      Protein synthesis inhibitors, actinomycin D and cycloheximide, were potent in
      inhibiting the SP-induced cortisol secretion. SDS-PAGE analysis, revealed that a
      240 kDa protein is newly synthesized in BAC cells in response to SP but not ACTH.
      It was also indicated that the production of this 240 kDa protein was elicited
      about 30 min after stimulation by SP. Moreover, A23187 and 12-O-tetradecanoyl
      phorbol-13-acetate (TPA) also caused a rapid [3H]leucine uptake and production of
      240 kDa protein. In contrast, dibutyryl cAMP did not induce the synthesis of this
      240 kDa protein. Calmidazolium, a calmodulin inhibitor, effectively inhibited not
      only [3H]leucine uptake but also 240 kDa protein production due to SP. On the
      other hand, KT-5720, an inhibitor of protein kinase A, had no effect on
      [3H]leucine uptake or 240 kDa production. Using the [125I]calmodulin-membrane
      overlay method, it was found that the 240 kDa protein was a newly synthesized
      calmodulin binding protein. From the present study, it was concluded that the de
      novo synthesis of this 240 kDa protein may be intimately related to the cortisol
      secretion in SP-stimulated BAC cells associated with an activation of the Ca
      calmodulin pathway.

PMID- 1384501
TI  - Inhibition of reverse transcriptase from feline immunodeficiency virus by analogs
      of 2'-deoxyadenosine-5'-triphosphate.
AB  - The replication of feline immunodeficiency virus (FIV) in cultured cells was
      inhibited by 2',3'-dideoxyadenosine (ddA) and by 9-(2
      phosphonylmethoxyethyl)adenine (PMEA) with IC50 values of 0.98 and 0.95 microM,
      respectively. The effects of the presumed active forms of these inhibitors, ddATP
      and PMEA-diphosphate (PMEApp), upon the FIV reverse transcriptase (RT) were
      examined with two different template-primer systems. Both of these compounds were
      potent inhibitors of the FIV RT in reactions with primed phi X-174 DNA, yielding
      Ki values of 8.8 nM for ddATP and 5.0 nM for PMEApp. However, they were both poor
      inhibitors of the reaction with poly(rU)-oligo(dA); concentrations of ddATP or
      PMEApp greater than 10 microM were required to inhibit this reaction by 50%.
      Further analysis of the reaction with poly(rU)-oligo(dA) revealed that even in
      the absence of inhibitors the primers were extended by less than 20 nucleotides.
      In contrast, high molecular weight products were obtained in reactions with phi X
      174 DNA. These results suggest that the reaction of FIV RT with poly(rU)
      oligo(dA) is not highly processive. The high degree of termination encountered
      during this reaction with poly(rU)-oligo(dA) may be responsible for the low
      inhibitory potential of ddATP and PMEApp.

PMID- 1384502
TI  - Practical usage concentrations of monensin have non-specific actions other than
      as a sodium ionophore in rat parotid acinar cells.
AB  - Monensin is used as a sodium ionophore to examine the effect of Na+ on cellular
      function in a variety of cell types. In the present study, we investigated the
      effects of different concentrations of monensin on the signal transduction system
      in exocrine parotid acinar cells. Monensin increased cytosolic free Na+
      concentration, measured by the Na+ indicator sodium-binding benzofuran
      isophthalate in a concentration-dependent manner (0.01 to 100 microM). Likewise,
      monensin concentration-dependently increased amylase release and intracellular
      Ca2+ concentration in the presence and the absence of extracellular Ca2+. Low
      concentrations (0.01 to 1 microM) of monensin did not release Ca2+ from non
      mitochondrial intracellular pools in permeabilized cells with saponin but high
      concentrations (10 and 100 microM) of monensin which are of practical usage did.
      Monensin itself did not change the cyclic AMP accumulation, whereas high
      concentrations (10 and 100 microM) but not low concentrations (0.01 to 1 microM)
      of monensin inhibited cyclic AMP accumulation elevated by isoproterenol in the
      presence and absence of extracellular Na+. These results indicate that high
      concentrations of monensin, which are practically used, have nonspecific actions
      in rat parotid acinar cells, and lower concentrations of monensin are recommended
      for use as a sodium ionophore.

PMID- 1384503
TI  - The chondroprotective drugs, Arteparon and sodium pentosan polysulphate, increase
      collagenase activity and inhibit stromelysin activity in vitro.
AB  - The effects of the chondroprotective drugs, sodium pentosan polysulphate (SP54)
      and Arteparon (glycosaminoglycan polysulphate), on the in vitro activities of the
      purified matrix metalloproteinases interstitial collagenase (matrix
      metalloproteinase 1, MMP1) and stromelysin (MMP3) were examined. Both drugs
      produced concentration-dependent enhancement of the degradation of type I
      collagen fibrils by purified human fibroblast collagenase and rat tumour
      collagenase. Rat collagenase activity was increased by drug concentrations above
      0.5 microgram/mL, whereas human collagenase activity was only increased by higher
      drug concentrations, above 5 micrograms/mL. The concentration dependence of the
      increase in rat collagenase activity was similar for both drugs, with a maximal 3
      fold increase at 50 micrograms/mL. In contrast, human collagenase activity was
      increased to a greater extent by SP 54 compared to Arteparon, with maximal
      increases at 5000 micrograms/mL of 6-fold and 2-4-fold, respectively. Both drugs
      produced concentration-dependent inhibition of the proteoglycan-degrading
      activity of both human fibroblast stromelysin and rat tumour stromelysin. Rat and
      human stromelysin activities were inhibited at drug concentrations above 0.005
      microgram/mL, with a similar concentration dependence for both drugs. Fifty
      percent inhibition of rat stromelysin was produced by concentrations of each drug
      in the 0.5-5 microgram/mL range. The pattern of inhibition of human stromelysin
      was similar, except that drug concentrations in the 500-5000 micrograms/mL range
      produced 50% inhibition. The possible modes of action for these drug effects and
      their possible pharmacological significance are discussed.

PMID- 1384504
TI  - Anti-human immunodeficiency virus effects of cationic metalloporphyrin
      ellipticine complexes.
AB  - A series of cationic metalloporphyrin-ellipticine complexes were found to inhibit
      the cytopathicity of human immunodeficiency virus type 1 (HIV-1) and simian
      immunodeficiency virus in MT-4 cells at concentrations ranging from 1.4 to 17
      micrograms/mL, i.e. at a concentration that was 2.5-30-fold below the
      cytotoxicity threshold. These compounds were also found to inhibit syncytium
      formation between persistently HIV-1-infected HUT-78 and uninfected Molt/4 cells,
      to interfere with HIV-1 binding to the cells, and to suppress HIV-1-associated
      reverse transcriptase activity.

PMID- 1384505
TI  - Absence of a direct coupling of a G protein to dihydropyridine binding sites in
      rat heart.
AB  - In rat heart membranes, the addition of guanine 5'-O-(3-thiotriphosphate) (GTP
      gamma-S), a stable GTP analogue, did not significantly modify the displacement of
      [3H]PN 200-110 binding by the 1,4-dihydropyridine (DHP) agonist Bay K 8644 and
      antagonists, nifedipine and nicardipine. These results are in agreement with some
      previously reported electrophysiological and pharmacological data, and they
      suggest that there is no direct involvement of a G protein in the modulation of
      DHP sensitive Ca channels in cardiac cells.

PMID- 1384506
TI  - [Effect of toxic components of snake venoms on binding of substance P with rat
      brain membranes].
AB  - Ion-exchange HPLC is used for purification of the snake venom alpha-neurotoxins,
      chi-bungarotoxin, cytotoxins, and phospholipases A2. Among these purified
      polypeptides, phospholipases A2 are found to be the most potent in inhibiting the
      substance P binding to rat brain membranes, Ki approximately 10(-8) M. Other
      toxins are weak inhibitors (Ki greater than or equal to 10(-4)-10(-5) M), earlier
      data on the inhibiting activity of alpha-bungarotoxin being caused by the
      commercial preparations' contamination with phospholipase A2.

PMID- 1384507
TI  - [Mono- and polyspecific glycoconjugates based on synthetic O-antigen determinants
      of Salmonella and their serological characteristics].
AB  - Mono- and polydeterminant synthetic antigens have been prepared via
      copolymerisation of acrylamide with allyl-, 2-acrylamidoethyl, and p
      acrylamidophenyl glycosides of di- and trisaccharides representative of the group
      specific Salmonella O-antigenic determinants (0:2, 0:3, 0:4, and 0:9).
      Serological specificity of the glycoconjugates obtained has been studied in
      enzyme immunoassay (EIA) using monoreceptor antisera.

PMID- 1384508
TI  - [Modulation of membrane activity of an enzyme in reversed micelle system with a
      change of media pH (using alkaline phosphatase as an example)].
AB  - Regulation of the membrane active properties of alkaline phosphatase from calf
      intestinal mucosa in reversed micelles of Aerosol OT (AOT) in octane was studied.
      The dependence of the catalytic activity on the surfactant concentration at the
      constant hydration degree, which characterises the membrane activity of enzymes,
      is modulated through pH variation. The variation may cause conformational changes
      of the protein molecule, resulting in exposition of anchor groups which provide
      the interaction of the enzyme with the micellar matrix.

PMID- 1384509
TI  - [Study of the antigenic structure of human immunodeficiency virus using synthetic
      peptides].
AB  - In a search for synthetic peptide antigens fit to detect anti-HIV antibodies, a
      set of algorithms were used to predict the probable antigenic determinants of
      gag, pol, env and nef proteins of HIV-1 and HIV-2. Over forty peptides were
      synthesized by the solid-phase method. The reactivity of the peptide antigens was
      evaluated in ELISA on panels of HIV-1/2-positive sera. Application of the
      synthetic peptides for the early HIV diagnostics was examined.

PMID- 1384510
TI  - Expression of human tenascin in synovitis and its regulation by interleukin-1.
AB  - OBJECTIVE: Tenascin is an extracellular matrix glycoprotein with effects on cell
      adhesion, cell migration, and lymphocyte activation. We proposed to identify the
      expression of human tenascin messenger RNA (mRNA) and protein in inflammatory
      synovitis and in normal synovium, and to identify potential regulatory cytokines.
      METHODS: Immunohistochemistry and in situ hybridization were used to identify the
      expression of tenascin in synovium. Northern blot analysis of RNA and both
      immunoblot analysis and enzyme-linked immunosorbent assay of proteins were used
      to identify tenascin in synovial cell cultures. RESULTS: Tenascin was found along
      the synovial lining layer and in perivascular areas of normal synovium. In
      inflammatory synovitis, tenascin protein and mRNA expression were shown to be
      increased in the synovial lining layer, in perivascular areas, in lymphoid
      aggregates, and in areas of fibrosis. Interleukin-1, a major mediator of tissue
      injury in inflammatory synovitis, induced tenascin expression and deposition in
      primary synovial fibroblast cultures. CONCLUSION: Tenascin mRNA and protein are
      increased in inflammatory synovitis, and interleukin-1 is an inducer of tenascin
      in synovial fibroblasts. This identifies a new pathway by which interleukin-1
      alters the extracellular matrix composition in synovitis. Since tenascin has
      effects on lymphocyte activation and cell adhesion, the induction of tenascin in
      inflammatory synovitis may play a role in the pathophysiology of arthritis.

PMID- 1384511
TI  - Changes in anti-U1 RNA antibody levels correlate with disease activity in
      patients with systemic lupus erythematosus overlap syndrome.
AB  - OBJECTIVE: To evaluate correlations between changes in anti-U1 RNA antibody
      levels and disease activity in 9 patients with systemic lupus erythematosus (SLE)
      overlap syndrome who were prospectively followed up for at least 3 years.
      METHODS: Anti-U1 RNA antibody levels were measured quantitatively, using a
      nitrocellulose filter binding assay. Disease activity was measured with a
      validated SLE activity index. RESULTS: All 9 major disease exacerbations were
      associated with peaks in anti-U1 RNA antibody level. CONCLUSION: These results
      seem to indicate that measuring anti-U1 RNA antibody levels can be useful for
      monitoring disease activity.

PMID- 1384512
TI  - Antibodies in rabbits immunized with cationized IgG react with histones H3 and
      H4.
AB  - OBJECTIVE: Rabbits immunized with cationized rabbit IgG develop antinuclear
      antibodies. This study was aimed at identifying the reactive antigens. METHODS:
      Rabbits were immunized with homotypic or allotypic IgG that were
      physicochemically altered to produce positively charged dimethylpropanamide
      (polycationic) side chains. RESULTS: Seven of 11 rabbits injected with cationized
      IgG produced antinuclear antibodies detected by indirect immunofluorescence. By
      enzyme-linked immunosorbent assay, these were IgG antibodies reacting with
      histone (H3-H4)2 tetramer and with individual histone polypeptides H3 and H4. The
      antihistone antibodies were absorbed by cationized IgG but not by normal IgG.
      CONCLUSION: Cationized IgG appears to possess antigenic determinants of
      sufficient similarity to produce antibody responses cross-reactive with histones
      H3 and H4.

PMID- 1384513
TI  - Antiphospholipid antibody/lupus anticoagulant workshop.

PMID- 1384514
TI  - Winners of the 1992 ACR slide competition and future plans for the clinical slide
      collection on the rheumatic diseases. The ACR Audiovisual Aids Subcommittee.

PMID- 1384515
TI  - A complex epitope: comment on the article by Mongey et al.

PMID- 1384516
TI  - Selection of T cell receptor V beta elements by HLA-DR determinants predisposing
      to rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is genetically linked to a sequence motif
      encoding for the middle portion of the alpha-helical loop, which is adjacent to
      the antigen-binding groove of the HLA-DR molecule. The disease-associated element
      might be involved in binding the antigen or in interacting with the T cell
      receptor (TCR). To investigate the contribution of the disease-associated element
      in T cell recognition events, we studied structural requirements in the
      interaction of T cell clones with HLA-DR determinants. METHODS: T cell clones
      restricted to disease-associated HLA-DR determinants were established by
      allogeneic stimulation of HLA-DRB1*0401+ or *0401- responders with HLA
      DRB1*0404/8+ stimulators. Allele specific primer sets were used to identify the V
      beta gene segment expressed by individual clones. Sequence analysis was applied
      to study the diversity of the TCR beta-chain junctional regions. RESULTS: The
      repertoire of TCR V beta elements was strongly biased toward the usage of V beta
      6. HLA-DRB1*0401+ and *0401- donors preferentially recruited V beta 6+ T cells to
      recognize the disease-associated HLA-DR determinant. Sequence data revealed that
      the V beta 6.6/7 and V beta 6.8/9 subtypes of the V beta 6 multigene family were
      overrepresented. The TCR beta chains were characterized by a high degree of
      junctional diversity, supporting the view that a multitude of peptide-DR
      complexes were recognized and that the preferential use of V beta 6 was dictated
      by the TCR beta chain-DR beta 1 chain contact. CONCLUSION: T cells reactive with
      the disease-associated HLA-DR structure are nonrandomly selected. The HLA-DR
      component predisposing to RA might define molecular requirements that restrict
      the TCR-HLA interaction. Thus, the phenomenon of HLA association in RA might
      reflect a genetic control of T cell recognition, through the selection of the TCR
      repertoire.

PMID- 1384517
TI  - [The effect of indomethacin and iloprost on the cardiodepressive actions of
      various anesthetics on isolated atrial preparations from guinea pigs].
AB  - Effects of Indomethacin and Iloprost on the Cardiodepressant Properties of
      Various Narcotics on Isolated Auricle Preparations from Guinea Pigs. In isolated
      auricle preparations from guinea pigs several narcotics (hexobarbital,
      pentobarbital, ketamine, etomidate, urethane) dose-dependently showed
      cardiodepressive effects. Premedication of the preparations with indomethacin
      significantly reduced the narcotics-induced changes of the cardiac action.
      Iloprost, a stable prostacyclin analogon, had the same efficacy. The influence of
      both substances could be due to an unspecific membrane effect or a positive
      inotropic action.

PMID- 1384518
TI  - Effect of gyrase inhibitors on some eukaryotic short-term test systems. DNase I
      in vitro nucleic acid synthesis and DNA repair in primary cultures of chicken
      embryo and rat cells.
AB  - DNase I activity was diminished by ciprofloxacin (CFL), nalidixic acid,
      norfloxacin, and ofloxacin in a dose-dependent manner, the MIC's (minimal
      significantly inhibiting concentrations) being 3.2, 2.8, 2.4, and 7.6
      micrograms/ml, resp., in phase I-reaction (increase in DNA hyperchromicity) and
      21, 20, 55, and 56 micrograms/ml, resp., in phase II-reaction (formation of acid
      soluble products). The Line-weaver-Burk plots indicated inhibition by substrate
      (phase I) and uncompetitive inhibition (phase II). The decrease in scheduled DNA
      synthesis by CFL showed MIC's of 270, 100, 1000, and 850 micrograms/ml in chicken
      embryo brain (B) and liver (L) cells and in rat thymic (T) and splenic (S) cells,
      resp. With regard to ribonucleic acid synthesis, MIC values of 82, 82, 12.5, and
      48 micrograms/ml CFL were determined, resp. Within a concentration range of 25
      1600 micrograms/ml, no principal differences existed between the 4-quinolones
      used. In T-cells, DNA repair as induced by X-irradiation or UV-light and
      determined by nucleoid sedimentation was inhibited by CFL (greater than 100
      micrograms/ml). The present results demonstrate biological effects of 4
      quinolones on eukaryotic systems at remarkably low concentrations. In this
      context, the possibility of interactions with DNA catabolizing enzyme systems and
      synergistic effects with DNA/chromatin-damaging agents should be considered
      further.

PMID- 1384519
TI  - Large-vessel endothelium switches to a microvascular phenotype during
      angiogenesis in collagen gel culture of rat aorta.
AB  - The purpose of this study was to investigate the vasoformative behavior in vitro
      of the native intimal endothelium of the rat aorta. To visualize the intimal
      surface directly, thoracic aortas were everted using a procedure that sequestered
      adventitial cells and possible remnant microvessels of periaortic soft tissues
      inside the aortic tube. Everted aortas embedded in collagen gel and cultured
      under serum-free conditions generated branching microvessels by a process of
      sprouting from the aortic intima. The newly formed microvessels originated from
      patches of activated intimal endothelial cells, which had survived the mechanical
      damage of the eversion procedure. Activated endothelial cells crawled over each
      other and engaged in lumen formation forming bilayers or multilayers of cells
      which became the source of sprouting histotypic microvessels. The endothelium of
      the newly formed microvessels was positive for factor VIII-related antigen and
      was partially surrounded by periendothelial cells which expressed alpha-smooth
      muscle actin. The results of this study indicate that the intimal endothelium of
      the rat aorta has considerable functional plasticity and can switch to a
      vasoformative phenotype in response to changes in the surrounding extracellular
      matrix environment.

PMID- 1384520
TI  - Relatively reduced values of plasma alpha-fetoprotein at early second trimester
      of pregnancies with hypertensive disorders.
AB  - Hypertensive disorders during pregnancy implicate placental pathologic
      conditions, which may interfere with the normal passage of alpha-fetoprotein
      (AFP) to the maternal blood. We compared the levels of maternal serum (MS) in
      early second trimester of pregnancies complicated by hypertensive disorders with
      those of matched controls. The distribution in the study group of MS-AFP multiple
      of median values was significantly different from the distribution in the control
      group. Moreover, up to multiple of the median 1.00, the number of hypertensive
      patients was larger than the number of normotensive pregnant women. The mean
      level of multiples of the median in the study group was significantly lower than
      that of the control group (p value = 0.003, 95% confidence interval: -0.30, 
      0.05). In the analysis of the distinct types of hypertension, the difference
      remained significant for 85 women in the moderate hypertension subgroup (p value
      = 0.032, confidence interval: -0.34, -0.02) and was not significant for the
      severe hypertension subgroup of 22 women (p value = 0.24, 95% confidence
      interval: -0.57, 0.15) and chronic hypertension subgroup of women (p value =
      0.52, 95% confidence interval: -0.44, 0.00). The trend was consistent in all the
      subgroups. Relatively low values of maternal serum AFP at early second trimester
      of pregnancies with hypertensive disorders may be a result of placental
      pathologic involvement and can help in the identification of the women at risk.

PMID- 1384521
TI  - Report of a case with aplasia cutis congenita, elevated amniotic fluid alpha
      fetoprotein, and positive acetylcholinesterase band.
AB  - A case report of a pregnant mother with elevated midtrimester maternal serum
      alpha-fetoprotein, an elevated amniotic fluid alpha-fetoprotein with a positive
      acetylcholinesterase band, and grossly normal fetal anatomy is presented. A
      premature female infant was delivered with bilateral symmetrical flank skin
      lesions consistent with the diagnosis of aplasia cutis congenita.

PMID- 1384522
TI  - [Analytical study of the Abbott and Ortho tests for screening and confirmation of
      anti-HCV antibodies. Le groupe de Travail "Hepatites virales" de la Societe
      Francaise de Transfusion Sanguine].
AB  - Anti-HCV systematic screening on blood donation was mandatory in France since
      first of March 1991. Two laboratories (Ortho-Chiron and Abbott) have introduced
      in Europe successively two kinds of hepatitis C positive diagnosis with 1st and
      2nd generation ELISA screening and confirmatory assays. The aim of this
      multicentric study was to evaluated the sensibility and specificity of these
      tests. For that, they used 10,090 blood sera. As a result we have seen that the
      new "second generation" screening assays have a higher sensitivity without less
      of specificity for the confirmatory tests.

PMID- 1384523
TI  - [Screening tests for anti-HCV antibodies: comparative results].
AB  - Comparative results between anti-HCV screening tests have shown better
      performances with 2nd generation tests than with 1st generation assays, since
      anti-C100-3 antibodies are less reliable and less durable than anti-C33 c and
      anti-C22-3 antibodies. Comparison between the four 2nd generation commercialized
      assays (Ortho, Abbott, Pasteur, Ubi-Organon) done on the hepatitis study group
      panel and on 109 samples from 18 patients collected before, during and after anti
      HCV seroconversion, has shown similar results for most of the samples but some
      discordances on samples with isolated anti-C100-3 or anti-C33 c antibodies. For
      the 18 patients, 3 discordances were observed between the four assays. These
      three discordances concerned 3 of the 6 seroconversions with anti-C33-c as the
      first detectable antibody. In two cases, Ubi-Organon assay did not recognize the
      seroconversion as early as the 3 other assays; in another case, it was the
      Pasteur assay which answered later than the other assays. As for the 15 other
      patients, no difference was observed between the four assays, in particular when
      anti-C22-3 was one of the first detectable antibodies.

PMID- 1384524
TI  - [Anti-HCV and recipients: situation in hemophiliacs in 1991].
AB  - Sera from 273 French haemophiliacs who had received non viral inactivated
      concentrates, were tested for antibodies to HCV by first and second generation
      assays. Antibodies to HCV were detected in 66% of the sera by the first
      generation assays (anti-C 100-3) reaching 100% by the second generation assays.
      None of the 53 patients only exposed to solvent-detergent treated Factor VIII or
      IX concentrates had HCV seroconversion. HCV core protein antibody was always
      detectable often as a single antibody in seropositive hemophilic patients.

PMID- 1384525
TI  - Monoclonal antibodies to malignant human gliomas.
AB  - Operationally specific monoclonal antibodies (MAbs) reactive with tumor but not
      normal adult tissues offer great potential for diagnosis and therapy of CNS
      neoplasms. Two targets for specific MAb localization were chosen for this study:
      (1) glioma-associated gangliosides GM2 [II3NeuAc-GgOse3Cer], GD2 [II3(NeuAc)2
      GgOse3Cer], GD3[II3(NeuAc)2-LacCer], 3'-isoLM1 [IV3NeuAc-LcOse4Cer], and 3',6'
      isoLD1 [IV3NeuAc,III6NeuAc-LcOse4Cer] and (2) epidermal growth factor receptor
      (EGFR) variant molecules. Epitopic specificity of isolated ganglioside hybridomas
      was determined with FAB-MS defined ganglioside standards. All MAb are IgM. Assay
      of 14 cytologic specimens and 31 frozen sections of primary CNS neoplasms
      revealed staining with anti-GD3 (14/14, 31/31), anti-GM2 (9/14, 26/31), and anti
      GD2 (6/14, 24/30), respectively. 3'-isoLM1 and 3',6' isoLD1, which exhibit a
      restricted oncofetal expression pattern and are not detectable in adult human
      brain, are present in 15/31 primary CNS neoplasms and in 1/8 human glioma
      xenografts, as detected by MAbs SL-50 and DMAb-14, respectively. EGFR proteins,
      the second target, have unique amino acid spans resulting from gene deletion in
      the amplified EGFR gene present in subsets of malignant human gliomas. Antibodies
      against EGFR deletion-mutant Type III show highly restricted activity with a
      subset of glioma biopsies (6/35) expressing the mutant EGFR. These reagents
      should be useful for in vitro and in vivo diagnosis and, potentially, for
      treatment of malignant brain tumors.

PMID- 1384526
TI  - Apoptosis of alpha beta T lymphocytes in the nervous system in experimental
      autoimmune encephalomyelitis: its possible implications for recovery and acquired
      tolerance.
AB  - We have recently shown that apoptosis, an active process of cellular self
      destruction, occurs in the central nervous system in Lewis rats with acute
      experimental autoimmune encephalomyelitis (EAE) induced by inoculation with
      myelin basic protein (MBP) and adjuvants. Conventional light and electron
      microscopic studies suggested that some of the apoptotic cells were
      oligodendrocytes and that others were hematogenous mononuclear cells. To
      determine whether any of the apoptotic cells were T lymphocytes, we used the
      technique of pre-embedding immunolabelling which allows sufficient preservation
      of the ultrastructure to permit recognition of apoptotic changes while at the
      same time preserving surface antigens so that the identity of the apoptotic cells
      can be determined by immunocytochemistry. Light microscopic immunocytochemistry
      using the monoclonal antibodies OX-34 (CD2) and R73 (alpha beta T-cell receptor)
      revealed that 10% of the CD2+ cells and 5% of the alpha beta T lymphocytes in the
      parenchyma of the spinal cord were dying by apoptosis. The presence of apoptotic
      alpha beta T cells was confirmed by electron microscopy. About half of all the
      apoptotic cells within the spinal cord were labelled by these antibodies. It is
      possible that some of the unlabelled apoptotic cells were also T lymphocytes but
      that others were glial cells such as oligodendrocytes. One possible
      interpretation of this T-cell apoptosis is that it represents activation-induced
      cell death, which has recently been shown to provide a mechanism of clonal
      elimination of mature as well as immature autoreactive T cells. Another possible
      interpretation is that it is a result of corticosterone released during the
      course of EAE. The apoptotic elimination of target-antigen-specific lymphocytes
      within the target organ in this autoimmune disease may contribute to the
      subsidence of inflammation and, if ongoing, to the development of tolerance.

PMID- 1384527
TI  - Delineation of tissue damage mechanisms in experimental autoimmune
      encephalomyelitis (EAE). I. Cell detachment and lysis induced by encephalitogenic
      CD4+ T lymphocytes.
AB  - Myelin basic protein (MBP) reactive CD4+ T lymphocytes, capable of inducing
      experimental autoimmune encephalomyelitis (EAE), were examined for their ability
      to damage target cells of central nervous system (CNS) origin. Damage was
      assessed by monitoring detachment of adherent astrocytes from substratum and
      astrocyte lysis. MBP-specific, but non-encephalitogenic CD4+ T cells mediated
      astrocyte detachment but not lysis. However, encephalitogenic CD4+ T cell lines
      were more efficient in causing astrocyte detachment and could also cause
      astrocyte lysis. The detachment and lytic activities of the MBP-reactive T cell
      lines tested were often independent of the presence of specific antigen, and were
      not restricted to syngeneic major histocompatibility (MHC) antigens. MBP often
      augmented the detaching and, if lytic, lytic activities of these T cells. The
      encephalitogenic CD4+ T cells also detached and lysed allogeneic 'bystander'
      fibroblasts in the presence of unlabelled syngeneic astrocytes, suggesting the
      involvement of a soluble mediator(s). Although MBP is essential for the
      initiation of EAE, the presence of MBP on cells of CNS origin, such as astrocytes
      and oligodendrocytes, does not appear to be necessary for their damage by MBP
      specific CD4+ T cells. Immune CD4+ T cells, which penetrate the CNS, may
      disorganize brain tissue structure by lysing astrocytes directly and by damaging
      other brain cells indirectly by soluble mediators. Thus cellular detachment, in
      addition to cell lysis, mediated by MBP-specific CD4+ cells may contribute to EAE
      pathogenesis.

PMID- 1384528
TI  - Delineation of tissue damage mechanisms in experimental autoimmune
      encephalomyelitis (EAE). II. Characteristics of astrocyte detachment mediated by
      myelin basic protein (MBP) specific CD4+ T lymphocytes.
AB  - We have shown that encephalitogenic, myelin basic protein (MBP)-specific CD4+ T
      cells can cause astrocyte and oligodendrocyte detachment in vitro. Similar
      processes may damage the central nervous system (CNS) in vivo by causing
      disorganization and destruction of brain tissue structure. The finding that
      'bystander' allogeneic fibrosarcoma cells were detached by MBP-specific CD4+ T
      cells only when syngeneic astrocytes were present, suggested that a soluble cell
      detaching factor (CDF) is released during the specific astrocyte-CD4+ effector
      interaction. In this study, CDF activity was detected in the supernatants of MBP
      reactive CD4+ T cells incubated with concanavalin A or astrocytes. Lymphocyte
      induced astrocyte lysis, but not detachment, was inhibited by the protein
      synthesis inhibitors, cycloheximide and puromycin, indicating that de novo
      protein synthesis is required for this type of lysis, but not for detachment.
      Astrocyte detachment was not inhibited, but rather augmented, by the trypsin
      inhibitors, soybean trypsin inhibitor (SBTI) and alpha-1-antitrypsin (alpha 1),
      suggesting that the CDF activity is not due to tryptic serine proteases, although
      it may be protease susceptible. The heparanase inhibitor, heparin, inhibited CD4+
      T cell-mediated astrocyte detachment at low doses, but augmented detachment at
      higher doses, indicating that detaching activity is not due to heparanases. The
      actin microfilament disrupting agent, cytochalasin B (CB), inhibited astrocyte
      detachment induced by MBP-specific CD4+ T cells. CB pretreatment of the target
      astrocytes, but not of the effector CD4+ T cells, inhibited astrocyte detachment,
      suggesting that the integrity of the target's, but not the effector's,
      cytoskeleton is required for astrocyte detachment. The results herein suggest
      that during astrocyte interaction with MBP-specific CD4+ T cells, soluble factors
      are released that trigger an intrinsic astrocyte detachment mechanism.

PMID- 1384529
TI  - Anti-CD4 monoclonal antibody therapy in severe psoriasis.
AB  - We report here the treatment of psoriasis, a chronic inflammatory skin disease
      characterized by uncontrolled keratinocyte proliferation, with BB14, a CD4 murine
      IgG1 antibody. Three patients with severe psoriasis were treated with anti-CD4
      mAb infusions (0.2 mg/kg/day for the first patient, 0.4 mg/kg/day for 2 days and
      0.8 mg/kg/day during the following days for the 2 others) for 7 or 8 days,
      without other therapy. Rapid clinical improvement, with major reduction of the
      Psoriasis Area Severity Index, was observed during 1 month after treatment.
      Moderate decreases in CD4+ blood cells occurred in the last two patients but not
      in the first one. Circulating T cells coated with anti-CD4 mAb were detectable
      during the first 48 h in the first patient and from day 1/2 to day 7/8 in the two
      others. The density of CD4 molecules on the surfaces of peripheral blood
      lymphocytes was decreased in all patients and remained low as long as anti-CD4
      mAb was detectable in patient serum. The maximal 24 h residual mAb levels ranged
      from 0.3 microgram/ml in the first patient to 3.8 and 7.0 microgram/ml in the two
      others. The three patients produced IgM antibodies against the anti-CD4 mAb at
      day 7/8 or 15 and two patients had IgG antibodies at day 15. Lesional skin
      samples demonstrated (1) gradual improvement in parakeratosis, papillomatosis and
      acanthosis, (2) decreased expression of ICAM-1 and HLA-DR by keratinocytes, (3)
      an increase in CD1a+ Langerhans cell number, (4) partial decrease in epidermal T
      cell infiltrate and (5) no major change in the dermal infiltrate composed of
      CD3+, TcR alpha beta+, CD45Ro+, HLA-DR+ T cells. We conclude that anti-CD4 mAb
      administration can induce a rapid and major improvement in psoriatic lesions,
      with immunohistochemical changes different from those induced by cyclosporin A or
      8-methoxypsoralen plus long wave UV light (PUVA) therapy. Our data provide strong
      evidence for a critical role of CD4+ lymphocytes in psoriasis.

PMID- 1384530
TI  - Cross-reactive maternal autoantibodies and congenital heart block.
AB  - Epitopes with linear sequences recognized by anti-La autoantibodies from seven
      mothers of children with congenital heart block were recently defined. Eight of
      these epitopes share sequence identity with three other proteins in addition to
      the original autoantigen, La. The three proteins are human cardiac myosin beta
      heavy chain, laminin B1 chain and the M6 protein of Streptococcus pyogenes.
      Affinity purified anti-La antibodies from a further three mothers bound to the La
      antigen and also to human cardiac myosin and mouse laminin. Affinity purified
      antibodies from three mothers of healthy children bound to the La antigen but
      showed minimal binding to either human cardiac myosin or mouse laminin. Cardiac
      myosin inhibited the binding of CHB-related anti-La antibodies to both La and
      myosin. These data support a role for maternal autoantibodies crossing the
      placenta and recognizing foetal cardiac antigens accessible at a critical
      developmental stage during gestation. We suggest that this would lead to
      complement fixation, inflammation and the subsequent pathology associated with
      congenital heart block.

PMID- 1384531
TI  - The beta-adrenoceptor-coupled adenylate cyclase system in rat C6 glioma cells.
      Deamplification by isoproterenol and oxaprotiline.
AB  - The beta-adrenoceptor-coupled adenylate cyclase system in rat C6 glioma cells
      displays many characteristics observed in brain tissue: using nonlinear
      regression analysis of agonist competition binding curves, we demonstrated that
      the bulk of beta-adrenoceptors show high nanomolar affinity for isoproterenol;
      like in brain tissue, Gpp(NH)p does not shift agonist competition binding curves
      to the right; and the agonist isoproterenol rapidly downregulates the number of
      beta-adrenoceptors and deamplifies the norepinephrine signal. However, unlike in
      brain tissue, where (-)-oxaprotiline fails to decrease the number of beta
      adrenoceptors and to desensitize the cyclic adenosine monophosphate generating
      system, it desensitizes the beta-adrenoceptor-coupled adenylate cyclase system in
      C6 glioma cells. Determination of the relative steady-state levels of beta
      adrenoceptor messenger ribonucleic acid (mRNA) by Northern blot analysis showed a
      twofold increase in the steady-state levels of the mRNA at 30 minutes following
      exposure to (-)-isoproterenol or (-)-oxaprotiline. At 48 hours, basal values of
      mRNA were observed at a time when beta-adrenoceptors were maximally decreased.
      Further experiments on transcriptional activation, and mRNA stability and
      translation will be required to unravel the complexity of agonist-dependent and
      agonist-independent regulation of beta-adrenoceptor density and function.

PMID- 1384532
TI  - Detection of interstitial increase in macrophages, characteristic of acute
      interstitial rejection, in routinely processed renal allograft biopsies using the
      monoclonal antibody KP1.
AB  - Acute interstitial rejection (AIR) of renal allografts is accompanied by a
      characteristic peritubular increase in macrophages, which can be identified with
      the CD14 monoclonal antibody (mAb) WT14 in cryostat sections. Since frozen tissue
      is not always available, we tested whether this increase can also be demonstrated
      in Bouin-fixed, paraffin-embedded biopsies, using the CD68 antimacrophage mAb
      KP1, which can also be applied to paraffin sections. Sections of 16 biopsies with
      AIR and 11 controls were stained with KP1. In 25 of the 27 biopsies, macrophages
      were strongly positive for KP1. Two AIR biopsies were completely negative,
      probably due to prolonged fixation. In the remaining 14 AIR biopsies, the number
      of KP1-positive cells was significantly higher than in the controls [1184 +/- 410
      per mm2 (mean +/- SD) vs 112 +/- 126 per mm2]. We conclude that, especially in
      cases in which frozen tissue is not available, the demonstration of increased
      numbers of monocytes/macrophages with mAb KP1 can be a helpful adjunct in the
      histological diagnosis of AIR in routinely processed renal biopsies.

PMID- 1384533
TI  - Recognition of synthetic peptides with sequences of rubella virus E1 polypeptide
      by antibodies and T lymphocytes.
AB  - Antigenicity of rubella virus E1 polypeptide was analyzed using synthetic
      peptides with predicted amino acid sequences. Overlapping solid-phase bound
      peptides were used to define antibody binding domains and a panel of free
      peptides to study T-cell responsiveness. Several antibody-binding areas including
      those earlier described to contain major neutralizing epitopes were recognized by
      human sera positive for rubella antibodies. T-cell lines specific for rubella
      virus were established from 14 rubella immune subjects. All cell lines responded
      to rubella virion-derived antigen but only eight (57%) responded to one or more
      of the synthetic peptides. Individual patterns of peptide recognition were found
      but peptide 8 representing amino acids 402-422 was most often stimulatory to T
      cells lines, either alone (3 subjects) or in combination with peptide 3 (amino
      acids 245-269) or 3 and 4 (amino acids 269-287). The response was HLA restricted
      but no single DR specificity for this restriction was identified.

PMID- 1384534
TI  - [A familial case of metabisulfite intolerance. Clinical and pharmacological
      study].
AB  - Within a context of a familial case of severe respiratory signs, with intolerance
      of sulfites and aspirin, we decided to study the clinical reliability of "in
      vitro" activation of human basophils in the presence of sulfites. Positivity of
      these tests for the three patients in the study (60, 73, and 66%) is confirmed by
      passive sensitization of donor basophils, which was destroyed when the serum was
      heated. This argument in favour of IgE dependence was strengthened by observation
      of an "in vitro" desensitization by an anti-IgE and not by an anti-IgG. These "in
      vitro" data are in agreement with the clinical history, daily routine of the
      patient, skin tests and where done, oral provocation tests.

PMID- 1384535
TI  - [In vitro simulation of rabbit cecal fermentation in a semi- continuous flow
      fermentor. II. Effect of inoculum type].
AB  - Two Rusitec fermentors were operated under identical conditions. One was seeded
      with an inoculum of rabbit caecal contents, and the other with bovine rumen
      contents. The fermentation substrate was rabbit feed that had been digested with
      amylase and pepsin. The substrate constituents (organic matter, OM and NDF) were
      lost in 48 h at a significantly higher rate in the presence of rumen inoculum
      (OM: +10%, NDF: +15%). The pHs of the 2 fermentors were similar at pH 6.6. The
      fermentors produced similar amounts of protein nitrogen per 24 h, after 6 d of
      adaptation. Volatile fatty acid production was slightly higher in the presence of
      rumen inoculum. The fermentor inoculated with rumen contents produced a higher
      percentage of propionic acid (25%) than of butyric acid (7%), while fermentation
      with rabbit caecal contents gave the opposite ratio (C3/C4 = 0.81). Consequently,
      only the rabbit caecal inoculum provided the fermentation profile characteristic
      of the species.

PMID- 1384536
TI  - The complement system in human reproduction.
AB  - Regulation of the complement system in reproduction is unique inasmuch as
      reproductive tissues represent the only condition where allogeneic interactions
      occur naturally. Both allogeneic extraembryonic membranes and semen that contact
      and interact with maternal cells and tissues must avert complement-mediated
      damage to ensure reproductive success. Several regulators of complement
      activation exist. Membrane cofactor protein (MCP) and decay accelerating factor
      (DAF) inactivate C3 and C5 convertases on cell surfaces. In addition, CD59
      inhibits the membrane attack complex (MAC) of the complement cascade. Strong
      expression of these membrane glycoproteins by trophoblast and amniotic epithelium
      has been observed. MCP, DAF, and CD59 likely safeguard extraembryonic tissues
      from complement damage originating from maternal and fetal blood or amniotic
      fluid. Different reproductive tract fluids vary in complement levels. With the
      exception of ovarian follicular fluid, these levels are generally much less than
      those in blood. Endometrial and cervical content of C3 appear to be regulated by
      hormones. These observations suggest that the effects of complement activation
      may vary in reproductive tissues. MCP is absent from the surfaces of oocytes.
      Sperm express MCP and DAF in discrete areas that would not be associated with the
      known complement-regulatory functions of these proteins. Seminal plasma contains
      MCP and the MAC inhibitor SP-40,40 but not DAF.SP-40,40 may exemplify how
      complement-regulatory proteins perform alternative functions as it interacts with
      molecules other than complement components. We have reviewed aspects of the
      complement system that relate to allogeneic interactions in reproduction and that
      suggest fruitful areas for further research.

PMID- 1384538
TI  - Physiological properties of GABAergic thalamic reticular neurons studied in
      vitro: relevance to thalamocortical synchronizing mechanisms.

PMID- 1384537
TI  - Angiogenesis in the uterus: potential regulation and relation to tumor
      angiogenesis.
AB  - Except under certain pathological conditions such as wound healing and solid
      tumor growth, angiogenesis is a relatively rare event in the adult. One
      exception, however, is the angiogenesis that occurs during the cyclical changes
      in the female reproductive tract. Many factors, chemical as well as mechanical,
      have been shown to be capable of promoting or inhibiting angiogenesis in vivo and
      in vitro. However, despite intense research efforts, the mechanisms involved in
      the regulation of angiogenesis in vivo are not fully understood. In this article
      we briefly review the basic steps involved in angiogenesis and present examples
      of factors and conditions that may serve as potential regulators of angiogenesis
      in the nonpregnant uterus. Finally, we discuss some of the architectural,
      anatomical, and physiological differences between the microcirculatory beds
      established during normal, self-limited vessel growth and that associated with
      the uncontrolled, pathological vascular growth that accompanies tumor growth and
      metastasis.

PMID- 1384539
TI  - Uncompetitive antagonist binding: a biochemical index of activation of the NMDA
      receptor-coupled ion channel.

PMID- 1384541
TI  - Functional alterations in GABAergic inhibition during activity.

PMID- 1384540
TI  - Amino acid neurotransmitter interactions in 'area tempestas': an epileptogenic
      trigger zone in the deep prepiriform cortex.

PMID- 1384542
TI  - Epileptogenesis and neuronal plasticity: studies on kainate receptor in the human
      and rat hippocampus.

PMID- 1384543
TI  - [Chemical constituents of Rhodiola kirilowii (Reg.) Reg].
AB  - Three compounds were isolated from the water-soluble part of alcohol extracts of
      rhizomes of Rhodiola kirilowii. Two of them were identified as salidroside and
      tyrosol, respectively by chemical and spectral analysis. beta-sitosterol was
      obtained from the petroleum extracts of the plant.

PMID- 1384544
TI  - [Influences of naomaitong upon cerebral blood flow in dogs].
AB  - This experiment has proven that the drug naomaitong can synchronously increase
      the blood flow of both dog's internal carotid artery and vertebral artery and
      also can antagonize the decrease of blood flow of both arteries caused by
      pituitrin. The increase of blood flow of both internal carotid artery and
      vertebral artery due to administration of naomaitong (1.2 g/kg) through the dog's
      duodenum is approximately equal to the increase of blood flow of both arteries
      resulting from the intramuscular injection of papaverine (1 mg/kg). Besides, the
      dosage of naomaitong is positively correlated to the effect and action of the
      drug.

PMID- 1384545
TI  - [Mechanisms of protective action of radix Salviae miltiorrhizae (RSM) against
      experimental hepatic injury in rats].
AB  - The results indicated that RSM could significantly inhibit the lipid peroxidation
      of normal livers and cultured hepatocytes of rats, induce liver microsomal
      cytochrome P450 in normal rats, increase nucleic acids, proteins, urea and
      cerolloplasmin of damaged cultured hepatocytes of rats, relieve ultrastructural
      damage of cultured hepatocytes induced by CCl4. The pharmacological actions
      mentioned above should be considered as important mechanisms of RSM against liver
      injury.

PMID- 1384546
TI  - HLA class I binding regions of HIV-1 proteins.
AB  - To identify HIV peptides containing HLA class I binding regions, different
      studies have been performed. These include the detection of interactions between
      HIV peptides and purified HLA molecules in solid-phase assays, the measurement of
      HLA molecule assembly in the presence of peptide added to cell lysates, and the
      detection of inhibition of CTL-mediated cytolysis by competition between peptides
      on target cells. To date, the HIV epitopes recognized by anti-HIV CTL are from
      the Env, Gag, Nef, and Pol proteins and they are identified using synthetic
      peptides of 12 to 20 amino acids. The search for a correlation between known HIV
      CTL epitopes and the results of HLA/peptide interaction assays reveals that: (1)
      most of the peptides that are positive in the assembly assay contain a HLA-A2
      peptide motif but the correlation between these positive peptides and the CTL
      epitopes is not obvious; (2) a high proportion of HIV epitopes are included in
      the peptides positive in solid-phase binding and in inhibition of cytolysis
      assays, although these tests do not allow us to predict HLA restriction; (3) the
      HLA-A2 peptide motif is not systematically included in HLA-A2-restricted CTL
      epitopes, this observation raising the possibility that other sequences are
      involved in HLA binding.

PMID- 1384547
TI  - Effects of hematopoietic growth factors on chemotherapy-induced myelosuppression.

PMID- 1384549
TI  - Electrophoretic pattern of the inter-alpha-inhibitor family proteins in human
      serum, characterized by chain-specific antibodies.
AB  - The inter-alpha-inhibitor (I alpha I) family encompasses four plasma proteins,
      namely free bikunin as well as I alpha I, pre-alpha-inhibitor (P alpha I) and
      inter-alpha-like inhibitor (I alpha LI). Each of the last three proteins is a
      distinct assembly of one bikunin chain with one or two out of three distinct,
      heavy (H) chains designated H1, H2 and H3. I alpha I is made of [H1 + H2 +
      bikunin], P alpha I is made of [H3 + bikunin] and I alpha LI is made of [H2 +
      bikunin]. We characterized various I alpha I family-related antisera/antibodies,
      including a reagent recognizing bikunin, another directed against the four H1,
      H2, H3 and bikunin chains, and a third one directed against both H1 and H2
      chains. By a simplified absorption procedure of the latter two antisera onto
      solid-phase immunoadsorbents made with i) purified I alpha I, or ii) a
      recombinant H1 polypeptide, we also obtained specific anti-H3 or anti-H2
      antibodies, respectively. This series of new antibodies was used to identify each
      component within the pattern of bands corresponding to I alpha I family in human
      serum, as separated by SDS-PAGE and western blotting.

PMID- 1384548
TI  - The heavy chains of human plasma inter-alpha-trypsin inhibitor: their isolation,
      their identification by electrophoresis and partial sequencing. Differential
      reactivity with concanavalin A.
AB  - Inter-alpha-trypsin inhibitor (ITI) is a complex protein made up of a light chain
      so-called bikunin and two heavy chains (apparent Mr values 96000 and 86000 in
      SDS/PAGE in non-reducing conditions). By sequence analysis, we clearly identified
      those two components as H1 and H2, respectively. We demonstrate that alkaline
      treatment (50mM NaOH during 5 min at room temperature) as well as chondroitinase
      digestion both lead to the dissociation of ITI. The conditions used for alkaline
      treatment were previously reported for cleavage of the covalent linkage between
      bikunin and H3 inside pre-alpha-trypsin inhibitor (Enghild et al. (1991) J. Biol.
      Chem. 266, 747-751). Carbohydrate analysis of the two heavy chains isolated by
      ion-exchange chromatography suggests the presence of complex-type N-glycans in
      both H1 and H2 and that of O-glycans in H2. H1 is eluted from Con-A Sepharose by
      alpha-methylmannoside, in agreement with the existence of at least one
      biantennary glycan chain. In contrast, H2 remains strongly bound to this support
      when submitted to the same conditions. Therefore this binding does not depend on
      carbohydrates. The capacity of H2 to develop such interactions is discussed with
      regard to the unusual bindings likely to exist between the different peptide
      chains constituting ITI.

PMID- 1384550
TI  - Isolation of a high-molecular mass glycoprotein from culture supernatant of an
      arthritogenic strain of the bacteria Erysipelothrix rhusiopathiae reacting with
      "inductive" monoclonal antibodies derived from rats with erysipelas
      polyarthritis.
AB  - A glycoprotein exhibiting a relative molecular mass of about 1000 kDa was
      purified to homogeneity from culture supernatant of arthritogenic bacteria
      (Erysipelothrix rhusiopathiae, strain T28) by ultrafiltration, ammonium sulfate
      precipitation, molecular mass exclusion, and ion exchange chromatography.
      Fractions obtained were analysed for their antigenic content by an enzyme linked
      immunosorbent assay (ELISA) using rabbit immune serum raised against this strain
      of Erysipelothrix rhusiopathiae. Distinct monoclonal antibodies obtained from
      rats suffering from erysipelas polyarthritis display a unique property by
      inducing very efficiently protective and regulatory mechanisms while being unable
      to generate classical "passive immunity". These "inductive" monoclonal antibodies
      recognize most likely linear epitopes on the purified glycoprotein. This makes it
      a prime source for analysing the target structure of these in vivo "inductive"
      antibodies.

PMID- 1384551
TI  - FK-506 and cyclosporin A: immunosuppressive mechanism of action and beyond.
AB  - Cyclosporin A and FK-506 are important therapeutic agents that have found
      widespread use in preventing graft rejection during tissue transplantation.
      Research efforts aimed at elucidating the molecular mechanism of action of these
      drugs have, in addition to defining their immunosuppressive functions, led to the
      identification of two new gene families whose products may function as components
      of several diverse signal transduction pathways. In the presence of the
      immunosuppressive drugs, some members of the receptor families interact with the
      Ca2+/calmodulin-dependent protein phosphatase 2B, also known as calcineurin.
      Inhibition of phosphatase activity may effect several downstream biochemical
      processes. In this way, cyclosporin A and FK-506 have proved to be useful probes
      of signaling events in both lymphocytic and other cell types.

PMID- 1384552
TI  - The semi-quantitative distribution and cellular localization of angiotensinogen
      mRNA in the rat brain.
AB  - The present study describes the regional distribution and cellular localization
      of angiotensinogen-mRNA in the rat brain as investigated by means of in situ
      hybridization also in combination with immunocytochemistry for glial fibrillary
      acidic protein. The angiotensinogen gene expression seemed to be restricted to
      astroglia and showed marked regional differences. In some areas angiotensinogen
      mRNA was present in almost all astrocytes with a strong signal (e.g. hypoglossal
      nucleus), whereas in other areas the angiotensinogen gene was expressed only in a
      certain population of glial cells. Some areas like the lateral septum were devoid
      of any detectable angiotensinogen-mRNA. A semi-quantitative atlas of the regional
      distribution of brain angiotensinogen-mRNA was obtained by using computer
      assisted microdensitometry and revealed considerable rostro-caudal fluctuations
      of the angiotensinogen-mRNA content of certain regions (e.g. the subfornical
      organ). Furthermore, a semi-quantitative analysis on the cellular level of
      angiotensinogen gene expression was performed showing a correlation of the
      angiotensinogen gene expression to the glia content of the regions examined. It
      was also demonstrated that the angiotensinogen gene expression had its highest
      levels in several distinct areas of the brain (e.g. the preoptic region and the
      hypothalamus), whereas other areas showed only low to moderate levels (e.g. the
      thalamus). The expression of the angiotensinogen gene in the rat brain was not
      only restricted to areas involved in cardiovascular and neuroendocrine control,
      but was also present in functionally different regions. Our data thus indicate
      that, based on the regional distribution of angiotensinogen-mRNA, angiotensin
      peptides may have other functions besides participation in cardiovascular and
      neuroendocrine control.

PMID- 1384553
TI  - Fine distribution of substance P-like immunoreactivity in the dorsal nucleus of
      the vagus nerve in cats.
AB  - The ultrastructure of substance P (SP)-immunoreactive elements in the cat dorsal
      motor nucleus of the vagus nerve was examined using pre- and post-embedding
      immunocytochemical procedures. Substance P-like immunoreactivity was observed in
      axon terminals and axon fibres which were mostly unmyelinated. Quantitative data
      showed that at least 16% of axon terminals contained SP. Their mean diameter was
      larger than that of their non-immunoreactive counterparts. Most (83%) SP
      containing terminals were seen to contact dendrites but some were observed
      adjoining soma or entirely embedded in the cytoplasm of vagal neurons (4.5%).
      Only 0.5% were observed to contact soma of internuerons. A few immunoreactive
      axon terminals (4%) were observed in contact with non-immunoreactive axon
      terminals. Round agranular vesicles and numerous dense core vesicles were visible
      in most SP-containing axon terminals (84.6%). The immunogold procedure showed the
      preferential subcellular location of SP to be dense core vesicles. In 32.4% of
      cases, SP-containing terminals were involved in synaptic contacts that were
      generally of the asymmetrical Gray type 1 and mainly apposed dendrites. The
      theoretical total of synaptic contacts was 74.5% and this suggests the existence
      of weak non-synaptic SP innervation involving approximately 25% of SP-containing
      axon terminals. No axo-axonic synapses were observed in the dorsal vagal nucleus.
      These results support the hypothesis that SP found in the dorsal vagal nucleus
      originates partly from vagal afferents and is involved in direct modulation of
      visceral functions mediated by vagal preganglionic neurons.

PMID- 1384554
TI  - Characterization of peptidergic efferents from the lateral parabrachial nucleus
      to identified neurons in the rat dorsal raphe nucleus.
AB  - The peptidergic content of the lateral parabrachial nucleus (LPB) efferents to
      the dorsal raphe nucleus (DRN) was studied by combining visualization of the
      anterogradely transported tracer Phaseolus vulgaris leucoagglutinin within fibers
      that were immunocytochemically stained for neurotensin (NT), calcitonin gene
      related peptide (CGRP) or galanin (GAL). The identity of DRN target neurons was
      determined with simultaneous immunocytochemical labelling for serotonin, the
      major transmitter within the nucleus. Within the DRN, we estimated that about two
      thirds of the anterogradely labelled fibers arising from the LPB also showed
      peptidergic immunoreactivity. NT was the most commonly observed neuropeptide in
      LPB neuronal efferents directed to the DRN, followed by CGRP and GAL. The
      peptidergic afferents in the DRN were oriented preferentially in the dorsoventral
      plane. Peptidergic fibers from the LPB possessed varicosities (diameters not
      exceeding 3 microns) and were apposed on serotoninergic neuronal somata. Some of
      the anterogradely labelled peptidergic fibers were not associated with cells
      showing immunoreactivity for serotonin. The present results suggest that NT
      ergic, CGRP-ergic and GAL-ergic neurons within the LPB are in contact with
      serotoninergic and non-serotoninergic neurons within the DRN. Since the DRN is
      known to project to the LPB, it is likely that bi-directional interconnections
      between these nuclei exist. Such linkages may provide anatomical substrates for
      coordinated autonomic responses.

PMID- 1384555
TI  - Multiple putative neuromessenger inputs to the phrenic nucleus in rat.
AB  - Immunohistochemical reactions for 12 putative neuromessengers combined with
      retrograde labeling of phrenic motoneurons identified seven neuromessengers (5
      hydroxytryptamine, substance P, thyrotropin-releasing hormone, methionine
      enkephalin, cholecystokinin, galanin, neuropeptide Y) located within terminal
      varicosities in the phrenic nucleus. The degree of terminal labeling in the
      phrenic nucleus varied depending on the peptide. Substance P, thyrotropin
      releasing hormone and methionine enkephalin were each tested for colocalization
      with 5-hydroxytryptamine within terminal varicosities in the phrenic nucleus, and
      the coincidence of double-labeling varied for each peptide. These results
      indicate that phrenic motoneurons are subject to modulation by many peptide
      neuromessengers that may alter their responsiveness to primary excitatory and
      inhibitory inputs.

PMID- 1384556
TI  - Subpopulations of neurons in the guinea-pig inferior mesenteric ganglia
      distinguished by the differential distribution of neurofilament triplet epitopes.
AB  - The distribution of the neurofilament protein triplet was examined in
      neurochemically identified subpopulations of neurons in the guinea-pig inferior
      mesenteric ganglion. A majority of the catecholamine-containing nerve cell bodies
      also contained the neurofilament protein triplet. However, a major proportion of
      the noradrenergic, neuropeptide Y-immunoreactive neurons did not contain
      neurofilament protein triplet immunoreactivity. Furthermore, a specific
      subpopulation of neurons that lacked catecholamines and were associated with the
      hypogastric nerve could be distinguished by the unusual feature of cell body
      content of post-translationally modified neurofilament protein triplet epitopes.
      These studies indicate that neurons in the inferior mesenteric ganglia can be
      distinguished by the presence of specific neurofilament protein triplet epitopes,
      and thus this class of intermediate filament proteins may confer specific
      properties to the neurons in which it is contained.

PMID- 1384557
TI  - The influence of HIV status on single and multiple drug reactions to
      antituberculous therapy in Africa.
AB  - OBJECTIVE: To document the influence of HIV status on drug reactions occurring in
      patients on antituberculous therapy in Harare, Zimbabwe. DESIGN: Retrospective
      cohort study. SETTING: City of Harare Tuberculosis Unit. PATIENTS: Records of 906
      patients with tuberculosis, of whom 162 reacted to antituberculous therapy, were
      analysed. RESULTS: Reactions to antituberculous drugs were more frequent in HIV
      positive (98 out of 363) than in HIV-negative (64 out of 543; P less than 0.0001)
      patients. The most common drug reaction was cutaneous hypersensitivity, occurring
      in 139 patients, 89 (64%) of whom were HIV-positive. Thiacetazone was implicated
      in 115 (82.7%) of the 139 cutaneous reactions and streptomycin in 10 (7.2%).
      Almost all cutaneous reactions occurred within 8 weeks of beginning treatment.
      Severe cutaneous reactions occurred more often in HIV-positive patients (P less
      than 0.001) and the only two deaths occurred in this group. Reactions to multiple
      drugs occurred in 18 HIV-positive and three HIV-negative patients (P = 0.017).
      CONCLUSIONS: The use of thiacetazone and streptomycin in antituberculous drug
      regimens should be reassessed in those countries where coinfection with HIV and
      tuberculosis is common.

PMID- 1384558
TI  - Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine
      hydrochloride on ischemia-induced changes in brain monoamines and their
      metabolites in gerbils.
AB  - Bifemelane hydrochloride (bifemelane), idebenone and indeloxazine hydrochloride
      (indeloxazine) are used clinically to reduce apathy and other emotional
      disturbances in patients with cerebrovascular disease. In gerbil brains, ischemia
      affects many monoaminergic neurotransmitters and their metabolites. In the
      present study, the effects of treatment with bifemelane, idebenone and
      indeloxazine on ischemia-induced changes in monoamines and their metabolites were
      studied in ischemic gerbil brains. Although these drugs had no effect on the
      monoaminergic neurotransmitters or their metabolites in sham-operated animals, in
      the ischemic brains both dopamine and serotonin turnovers were abnormal after
      idebenone or indeloxazine treatment. Bifemelane, in contrast, tended to correct
      the ischemia-induced changes in the dopaminergic and serotonergic systems in the
      cerebral cortex, hippocampus and thalamus + midbrain. From the present results
      and those in previous reports, we conclude that bifemelane is more appropriate
      than idebenone or indeloxazine as a treatment for the ischemia-induced changes in
      monoaminergic neurotransmitter systems.

PMID- 1384559
TI  - Sympathetic denervation and chronic serotonin uptake blockade by fluoxetine do
      not affect pineal gland 5-hydroxyindole acetic acid: evidence that oxidative
      deamination of pineal serotonin is a property of the pinealocyte.
AB  - This investigation tested the hypothesis that oxidative deamination of 5HT in the
      pineal gland occurs primarily in cellular compartments other than the pinealocyte
      (i.e., noradrenergic nerve terminals and glia). Following sympathetic denervation
      of the pineal gland by bilateral superior cervical sympathectomy, pineal levels
      of 5HT and its oxidative metabolite, 5HIAA, were measured by HPLC from samples
      collected at six time points over the 24 h photoperiod. The role of glia in 5HT
      deamination was further examined by chronic treatment with the 5HT uptake
      blocker, fluoxetine (10 mg/kg). Sympathectomy abolished the circadian rhythms of
      both 5HT and 5HIAA, but had no statistically significant effect on the ratio of
      5HIAA/5HT compared to sham-operated and intact controls over the 24 h period.
      Pineal daytime levels of both 5HT and 5HIAA were unaffected by fluoxetine
      treatment. These findings indicate that the pinealocyte is an important cellular
      compartment for 5HT oxidative metabolism.

PMID- 1384560
TI  - [Effects of administration of three kinds of catecholamine on mitral complex].
AB  - To evaluate cardiac injury induced by injection of 3 kinds of catecholamine, 219
      male rabbits were examined. Eighty-five to 100 percent of the animals having high
      doses of adrenaline and noradrenaline showed ventricular premature contraction,
      and 65 to 75 percent of them showed mitral complex injury; whereas, these effects
      were identified in none or only in 10 percent of the animals with isoproterenol
      injection. The cardiac injury was similar to that of vagal stimulation, which was
      reported previously. These results indicate that ventricular premature
      contractions are important for developing the adrenaline- and noradrenaline
      induced mitral complex injury.

PMID- 1384561
TI  - Chronic ear pathology in a model of neonatal amniotic fluid ear inoculation.
AB  - Human histopathologic studies have demonstrated that amniotic fluid cellular
      contents, keratinized squamous epithelial cells and lanugo hair, induce an
      intense inflammatory reaction including granulation tissue in the neonatal
      temporal bone. To investigate this reaction over a prolonged period, an animal
      model was studied. An aliquot of sterilized autologous hair and keratinized
      epithelial cells was placed into 14 gerbil bullae; saline was used as a
      contralateral control. The animals were sacrificed at intervals up to 6 months
      and the temporal bones were studied by light microscopy. All animals demonstrated
      nonpurulent inflammatory changes on the experimental side including granulation
      tissue, osteoneogenesis, tympanosclerosis, and cholesteatoma; the control side
      demonstrated minimal middle ear changes. We conclude that in this model
      autologous keratinized tissue provokes a foreign body response similar to the
      granulation tissue observed in human infants and, further, that over a prolonged
      period the middle ear demonstrates more severe pathologic consequences.

PMID- 1384562
TI  - Reflectance method for simple determination of proteinase activity in microliter
      samples of a complex serum-like fluid.
AB  - A technique using an optical instrument, a reflectometer, for quantitative
      determination of proteinase activity in microliter samples of complex serum-like
      fluids, e.g., crevicular exudate from single sites, was developed. The technique
      allowed the use of various proteins as enzyme substrate. The reflectometer
      measures the mass of a layer, such as protein, adsorbed to a reflecting surface.
      This is done by measuring the reflected light intensity of the p-polarized light
      beam on a surface. We used methylized silicon surfaces that were coated with
      fibrinogen, alpha 2-macroglobulin, or hemoglobin as enzyme substrates. The test
      solution was incubated overnight in a basin made in an agar gel applied on the
      top of the protein-coated surface. In 82 exudates from periodontitis sites, with
      pocket depths greater than or equal to 6 mm, fibrinogenolytic activity
      corresponding to 1 microgram ml-1 of trypsin and pronase P was found in 20% of
      the samples.

PMID- 1384563
TI  - The application of aqueous two-phase systems to oligosaccharide synthesis by
      alpha-mannosidase catalysed glycosyl transfer reactions.
AB  - Aqueous two-phase systems formed from PEG and dextran have been applied to the
      synthesis of oligosaccharide by Jack bean alpha-mannosidase in reverse. Whilst
      rates of synthesis and percentage yields were similar in two-phase systems and
      one-phase aqueous buffer systems, a ten-fold increase in yield of product per
      unit of enzyme was seen. In addition, the use of aqueous two-phase systems offers
      potential process advantages over one-phase systems for the synthesis of
      oligosaccharides.

PMID- 1384564
TI  - Distribution of an enzyme in porous polymer beads.
AB  - Trypsin has been immobilized by adsorption onto Amberlite XAD-7 beads. The
      Michaelis constant (Km) of the enzyme was increased about sevenfold following the
      immobilization. Its rate of penetration into the porous beads was determined by
      staining the beads, which had been split, with naphthol blue black. The extent of
      diffusional rate limitation of immobilized trypsin was related to the penetration
      depth of the enzyme into the beads. This can be controlled by manipulating the
      conditions during the preparation of the immobilized enzyme.

PMID- 1384565
TI  - DNA polymorphism studies. Approaches to elucidating multifactorial ischaemic
      heart disease: the apo B gene as an example.
AB  - It is well established that elevated plasma levels of low-density lipoprotein
      (LDL) particles are a risk factor for ischaemic heart disease with the
      distribution in LDL levels seen in the general population being the result of
      interaction between environmental factors, such as dietary fat intake, and
      genetic variation that is present in different individuals. One of the candidate
      genes where such variation is likely to occur, is the gene coding for
      apolipoprotein B (apo B). Many studies have reported an association between a
      common polymorphism of the apo B gene, detected using the restriction enzyme
      XbaI, and differences in plasma lipid levels, explaining 3-5% of the variance in
      LDL-cholesterol levels in samples representative of the healthy population. It
      has been proposed that the mechanism of this association is due to functional
      amino acid changes within the apo B protein, that affect LDL catabolism by
      altering binding affinity to the LDL-receptor. Several amino acid substitutions
      in the apo B gene have now been characterized, and these form the basis of the
      different epitopes that create the Ag marker system. Previous studies have
      reported that the Ag(x) epitope is associated with lower plasma lipid levels, and
      until recently the molecular basis for this association has been unclear. We have
      determined that the Ag(x) epitope is associated with both a Pro-Leu2712, and Asn
      Ser4311 substitution, with the Leu-Ser allele being associated with significantly
      lower levels of plasma lipids in a sample of healthy individuals from
      Sweden.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384566
TI  - Language intervention with children who have developmental delays: effects of an
      interactive approach.
AB  - The interactive model of language intervention instructs parents to use
      techniques that promote reciprocal social interactions and facilitate the
      development of communication and language abilities. In this evaluation study, 32
      mothers and their preschool-age children with developmental delays were randomly
      assigned to treatment and control (delayed treatment) groups. Consistent with the
      interactive model, mothers in the treatment group became more responsive, less
      directive, and provided clearer linguistic models. Furthermore, these changes
      were maintained for at least 4 months after intervention, and involvement in the
      parent-centered intervention program did not increase maternal stress. More
      important, these changes were accompanied by concomitant increases in children's
      use of vocal turns. Contrary to predictions, developmental improvements in
      children's communicative and linguistic abilities were comparable in both groups.
      Findings suggest that an interactive model may afford a useful adjunct to other
      intervention approaches by instructing parents on how to promote children's use
      of existing abilities, but an interactive model may have no effect on language
      acquisition of at least some children with developmental delays.

PMID- 1384567
TI  - Do children with developmental delays use more frequent and diverse language in
      verbal routines?
AB  - The current study is the first to test the hypotheses that children with
      developmental delays use more frequent language and more diverse vocabulary in
      routines than in nonroutines. The 19 child participants were in Brown's (1973)
      first stage of language learning. Using a novel method of measuring routines, 18
      of the parents identified at least one routine in a videotaped play session with
      their children. Results support both hypotheses and provide descriptive
      information about the content of the routines displayed by the parents and
      children in the free-play context. The importance of replicating the findings in
      the context of an experimental design before concluding that "routineness" caused
      the children to talk more often and with more diverse vocabulary was emphasized.

PMID- 1384568
TI  - Early language and communicative abilities of children with periventricular
      leukomalacia.
AB  - Ten 2-year-old children with periventricular leukomalacia (PVL), a brain injury
      associated with prematurity, were evaluated using language samples. Five children
      scored less than 80 on cognitive testing (delayed). Five children with this
      disorder and normal cognitive scores were assessed at two ages, matched with the
      delayed group on CA and developmental level. The delayed group produced
      significantly fewer lexical tokens and spontaneous verbal utterances than did the
      CA-matched group. No significant differences were observed between the delayed
      group and either comparison group on other measures of lexicon, grammar, or
      communication. The data demonstrate a relation between cognitive abilities and
      measures of verbal productivity in children with PVL.

PMID- 1384569
TI  - Vocal development in infants with Down syndrome and infants who are developing
      normally.
AB  - The development of early vocalizations was investigated with 13 infants who had
      Down syndrome and 27 infants who were developing normally at bimonthly intervals
      from 4 to 18 months of age. A perceptually based framework was used to categorize
      utterances according to their developmental relations with adult, well-formed, or
      "canonical" syllables. Over time, both groups demonstrated increased production
      of mature vowel and canonical consonant-vowel syllables (characterized by full
      vowels, consonants, and rapid, well-coordinated articulatory movements) and
      decreased production of less mature "quasi-vowel" and marginal syllables. Infants
      in both groups were also quite variable in vocal development, both within group
      and across time.

PMID- 1384571
TI  - A high sensitivity method for sequencing RNA: application to ribosomal RNA.

PMID- 1384570
TI  - Micrometastases from squamous cell carcinoma in neck dissection specimens.
AB  - The incidence of micrometastases in cervical lymph nodes from squamous cell
      carcinomas of the head and neck was studied using routine histopathological
      examination. Micrometastases were found in 66 lymph nodes in 41 of the 92 tumor
      positive neck dissection specimens. The detection of these micrometastases
      influenced postoperative treatment in 3 of the 77 patients with neck node
      metastases. The value of additional sectioning for detecting micrometastases was
      thus assessed. Sectioning at a deeper level in 600 originally histopathologically
      negative lymph nodes from 64 patients revealed 7 additional micrometastases in 5
      patients. Antikeratin staining with a mixture of two monoclonal antibodies (AE1
      and AE3) revealed 4 micrometastases in 739 originally histopathologically
      negative lymph nodes in 3 of 13 patients studied. Because of the unknown
      prognostic significance of micrometastases and the consequent arbitrary
      consequences for postoperative treatment, present findings show that the extra
      workload of immunostaining and deeper sectioning does not warrant their routine
      use in clinical practise.

PMID- 1384572
TI  - Semi-dry electroblotting of DNA and RNA from agarose and polyacrylamide gels.
AB  - Semi-dry electroblotting of nucleic acids was originally of interest for its
      speed and convenience, but it had significant limitations in reliability of
      transfer. This work describes optimalization of the buffer systems and general
      conditions for use that enable the semi-dry method of nucleic acids transfer to
      yield quantitative, fast and reliable results.

PMID- 1384573
TI  - Developmental regulation of an snRNP core protein epitope during pig
      embryogenesis and after nuclear transfer for cloning.
AB  - The appearance and stabilization of a core protein epitope of the snRNP is
      developmentally regulated during pig embryogenesis. The epitope recognized by the
      monoclonal antibody Y12 is present in the germinal vesicle of mature oocytes and
      interphase nuclei of late 4-cell stage (24 to 30 hours post cleavage to the 4
      cell stage) to blastocyst stage embryos. There was no antibody localization
      within pronuclei, or nuclei of 2-cell or early 4-cell stage embryos. Zygotes or 2
      cell stage embryos cultured in the presence of alpha-amanitin to the late 4-cell
      stage showed no immunoreactivity, whereas control embryos had immunoreactivity.
      Thus antibody localization was correlated with RNA synthesis and RNA processing
      that begins by 24 hours post cleavage to the 4-cell stage. A final experiment
      showed no detectable immunoreactivity in 16-cell stage nuclei that had been
      transferred to enucleated activated meiotic metaphase II oocytes. Since
      immunoreactivity is associated with active RNA synthesis and RNA processing, it
      suggests that the 16-cell stage nucleus, which is RNA synthetically active, does
      not process RNA after nuclear transfer to an enucleated activated meiotic
      metaphase II oocyte.

PMID- 1384574
TI  - A comparison of two autoradiographic methods for detecting radiolabeled nucleic
      acids in embryos.
AB  - Two methods for preparing embryos for autoradiographic study of newly synthesized
      nucleic acids are described and compared. The first method consists of rapidly
      fixing radiolabeled embryos with acetic acid:methanol, spreading them on glass
      slides and exposing them for 8 days with a photographic emulsion. The second
      method consists of fixing, embedding in resin, and sectioning the embryos before
      their exposure with the emulsion for 3 weeks. Both techniques have many
      applications in studies of early embryonic activity, but the spread technique is
      very sensitive, simpler, and faster.

PMID- 1384575
TI  - Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor
      induced differentiation.
AB  - To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth
      factor (NGF)-induced differentiation, we have overexpressed gp140trk in the NGF
      responsive PC12 cell line. Here we demonstrate that overexpression of gp140trk
      results in marked changes in NGF-induced differentiation. Whereas PC12 cells
      elaborated neurites after 2 days of continuous exposure to NGF, PC12 cells
      overexpressing gp140trk by 20-fold(trk-PC12) began this process within hours.
      Compared with wild-type PC12 cells, trk-PC12 exhibited an increase in both high
      and low affinity NGF-binding sites. Furthermore, trk-PC12 cells displayed an
      enhanced level of NGF-dependent gp140trk autophosphorylation, and this activity
      was sustained for many hours following ligand binding. The tyrosine
      phosphorylation or activity of several cellular proteins, such as PLC-gamma 1, PI
      3 kinase, and Erk1 and the expression of the mRNA for the late response gene
      transin were also sustained as a consequence of gp140trk overexpression. The data
      indicate that overexpression of gp140trk in PC12 cells markedly accelerates NGF
      induced differentiation pathways, possibly through the elevation of gp140trk
      tyrosine kinase activity.

PMID- 1384576
TI  - Intracellular Ca2+ regulates the sensitivity of cyclic nucleotide-gated channels
      in olfactory receptor neurons.
AB  - In olfactory receptor neurons, odorants stimulate production of cAMP, which
      directly activates cyclic nucleotide-gated (CNG) channels. Olfactory adaptation
      is thought to result from a rise in intracellular Ca2+. To determine whether
      inhibition of CNG channels plays a role in adaptation, we have investigated the
      action of Ca2+ on these channels in inside-out "macro" patches from the dendrite
      and cilia of catfish olfactory neurons. Internal Ca2+, with a K1/2 of 3 microM,
      profoundly inhibits CNG channels by shifting the dose-response relationship to
      higher cAMP levels without altering the maximal response. The inhibition does not
      appear to result from a direct interaction of Ca2+ with the CNG channel. Thus,
      the inhibition washes out after excision of the inside-out patch, and Ca2+ does
      not inhibit the cloned catfish CNG channel expressed in Xenopus oocytes. Hence we
      propose that a regulatory Ca(2+)-binding protein, distinct from the CNG channel,
      controls the gain of signal transduction and contributes to olfactory adaptation
      by decreasing the sensitivity of the CNG channel to cAMP.

PMID- 1384577
TI  - Plasma membrane inositol 1,4,5-trisphosphate-activated channels mediate signal
      transduction in lobster olfactory receptor neurons.
AB  - Inositol 1,4,5-trisphosphate (IP3) selectively evokes an inward (excitatory)
      current in cultured lobster olfactory receptor neurons (ORNs) and directly
      activates two types of channels in cell-free patches of plasma membrane from the
      ORNs. The IP3-activated channels have kinetic properties of odor-activated
      channels in the ORNs and pharmacological properties of intracellular IP3
      activated channels in other systems. An antibody directed against an
      intracellular, cerebellar IP3 receptor recognizes a protein with a molecular
      weight similar to the mammalian receptor in the ORNs. The antibody selectively
      increases odor-evoked inward currents and IP3-activated unitary currents in the
      ORNs. The data provide further evidence for IP3 as an olfactory second messenger
      and implicate at least one and possibly two novel plasma membrane IP3 receptors
      in olfactory transduction.

PMID- 1384578
TI  - Activation and desensitization of glutamate-activated channels mediating fast
      excitatory synaptic currents in the visual cortex.
AB  - Brief glutamate applications to membrane patches, excised from neurons in the rat
      visual cortex, were used to assess the role of desensitization in determining the
      AMPA/kainate receptor-mediated excitatory postsynaptic current (EPSC) time
      course. A brief (1 ms) application of glutamate (1-10 mM) produced a response
      that mimicked the time course of miniature EPSCs (mEPSCs). Direct evidence is
      presented that the rate of onset of desensitization is much slower than the decay
      rate of the response to a brief application of glutamate, implying that the decay
      of mEPSCs reflects channel closure into a state readily available for
      reactivation. Rapid application of glutamate combined with nonstationary variance
      analysis provided an estimate of the single-channel conductance and open
      probability, allowing an approximation of the number of available channels at a
      single synaptic site.

PMID- 1384579
TI  - Evaluation of a respiratory rate monitor in postsurgical patients.
AB  - STUDY OBJECTIVE: To evaluate the clinical use of a cardiorespiratory rate monitor
      in patients receiving epidural opioids following major surgery. DESIGN: For 6
      hours during the night following surgery, patients were continuously monitored
      with a cardiorespiratory rate monitor and a pulse oximeter, as well as by an in
      room observer. SETTING: Postoperative surgical ward at a university hospital.
      PATIENTS: Eight ASA physical status I and II patients ages 30 to 76 years.
      INTERVENTIONS: Any bradypneic, hypoxemic, bradycardic, or tachycardic event was
      confirmed by the observer and recorded. MEASUREMENTS AND MAIN RESULTS: The
      cardiorespiratory rate monitor accurately identified true bradypneic episodes in
      five of the eight patients. There were no false-positive alarms. The respiratory
      rate monitor and the pulse oximeter identified one episode of hypoxemia. There
      were no episodes of bradycardia or tachycardia. CONCLUSIONS: The
      cardiorespiratory rate monitor is useful in patients at risk for bradypnea
      following surgery.

PMID- 1384580
TI  - Cytokines and lipopolysaccharide induce nitric oxide synthase in cultured rat
      pulmonary artery smooth muscle.
AB  - In the current study, we describe cytokine and Escherichia coli
      lipopolysaccharide (LPS) induction of nitric oxide (NO) synthase mRNA levels in
      cultured smooth muscle from rat pulmonary artery (RPASM). Exposure of RPASM to
      interleukin-1 beta, interferon-gamma, or LPS alone did not significantly affect
      NO synthesis, as determined by nitrite concentrations in media. Exposure to tumor
      necrosis factor-alpha caused a modest (2x) increase in nitrite production. In
      contrast, exposure to a combination of the above three cytokines and LPS caused a
      large increase in NO synthesis. Exposure of RPASM to this combination caused an
      increase in mRNA levels of NO synthase (as described by Northern blot analysis
      with 32P-cDNA probe to an inducible form of NO synthase present in murine
      macrophages) that was apparent as early as 4 h. Expression of the induced gene
      product after exposure to the cytokine and LPS mixture was evident by significant
      increases in nitrite production at 12 h. Production of nitrite was completely
      abolished in the presence of NG-monomethyl-L-arginine (NMA), and this inhibition
      was reversible by the addition of excess L-arginine. NO synthase mRNA levels were
      not affected by NMA. The nitrite production induced by the combination of
      cytokines and LPS was abolished by pretreating cells with cycloheximide. These
      data indicate that a combination of cytokines and LPS affect expression of the
      gene for the inducible form of NO synthase in cultured RPASM.

PMID- 1384581
TI  - Carboxypeptidase M-like enzyme modulates the noncholinergic bronchoconstrictor
      response in guinea pig.
AB  - We studied the effects of aerosolized DL-2-mercaptomethyl-3-guanidino
      ethylthiopropanoic acid (MGTA) (10(-4) M, 90 breaths), a specific inhibitor of
      carboxypeptidase B-type enzymes, on changes in total pulmonary resistance (RL)
      induced by aerosolized capsaicin (10(-7) to 10(-4) M; 10 breaths at each
      concentration) and vagus nerve stimulation (5 V, 5 ms, for 20 s at frequencies
      varying from 2 to 10 Hz) in anesthetized, atropinized, and ventilated guinea
      pigs. We also studied the effect of aerosolized MGTA on the bronchoconstrictor
      response to either aerosolized substance P, neurokinin A (10(-7) to 10(-4) M; 10
      breaths at each concentration), and carbachol (10(-5) to 2 x 10(-4) M; 10 breaths
      at each concentration) or to i.v. administration of neurokinin A (10(-11) to 10(
      8) mol/kg), bradykinin (10(-10) to 10(-7) mol/kg), and histamine (10(-8) to 10(
      6) mol/kg). Although aerosolized MGTA caused no change in basal RL (P > 0.5), it
      did potentiate the noncholinergic bronchoconstrictor response to capsaicin (n =
      5; P < 0.001) as well as to vagus nerve stimulation (n = 5; P = 0.001). In
      contrast, MGTA did not potentiate the bronchoconstrictor response to either
      aerosolized substance P, neurokinin A, and carbachol or to i.v. administration of
      neurokinin A, histamine, and bradykinin. Carboxypeptidase activity cleaving C
      terminal arginine or lysine was found in the membrane preparations of trachea and
      lung from guinea pigs. The membrane-bound carboxypeptidase activity was maximal
      at pH 7.0 and was enhanced by the presence of CoCl2 (1 mM) in both the tracheal
      and lung tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384582
TI  - Differential localization of the cystic fibrosis transmembrane conductance
      regulator in normal and cystic fibrosis airway epithelium.
AB  - Deletion of the amino acid residue Phe 508 of the cystic fibrosis transmembrane
      conductance regulator (CFTR) protein represents the most common mutation
      identified in cystic fibrosis (CF) patients. A monoclonal and a polyclonal
      antibody directed against different regions of CFTR were used to localize the
      CFTR protein in normal and CF airway epithelium derived from polyps of non-CF and
      CF subjects homozygous for the delta Phe 508 CFTR mutation. To identify the
      cellular and subcellular localization of CFTR, immunofluorescent light
      microscopy, confocal scanning microscopy, and immunogold transmission electron
      microscopy were performed on cryofixed tissue. A markedly different subcellular
      distribution was identified between normal and CF airway epithelial cells. In
      normal epithelium, labeling was restricted to the surface apical compartment of
      the ciliated cells. In contrast, in the epithelium from homozygous delta Phe 508
      CF patients, CFTR markedly accumulated in the cytosol of all the epithelial
      cells. These findings are consistent with the concept that the CFTR delta Phe 508
      mutation modifies the intracellular maturation and trafficking of the protein,
      leading to an altered subcellular distribution of the delta Phe 508 mutant CFTR.

PMID- 1384583
TI  - Bronchial epithelial cell-derived cytokines (G-CSF and GM-CSF) promote the
      survival of peripheral blood neutrophils in vitro.
AB  - Neutrophil accumulation in the respiratory tract occurs in a variety of
      inflammatory disorders, particularly those associated with cigarette smoking. We
      examined whether bronchial epithelial cells could contribute to this accumulation
      through the production of factors that increased the survival of neutrophils.
      Pure primary cultures of human bronchial epithelial cells (HBEC) were used to
      generate conditioned medium (CM), and the effect of this CM on the survival of
      neutrophils in vitro was examined. When neutrophils were cultured in control
      medium, survival was 8.7 +/- 1.7% at 72 h. In contrast, culture of neutrophils in
      CM resulted in a dose-dependent increase in survival: 22.6 +/- 5.5, 43.6 +/- 4.2,
      and 64 +/- 3.8% in 1, 10, and 50% CM respectively (mean +/- SEM; P < 0.05). As
      evidenced by the examination of neutrophil DNA, this prolongation of survival was
      associated with suppression of apoptosis. Cytokines with known actions on
      neutrophil biology identified in the CM included granulocyte colony-stimulating
      factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and
      interleukin-8. Through the use of specific neutralizing antibodies, G-CSF and GM
      CSF were identified as promoting neutrophil survival. Neutrophil survival was
      prolonged in the presence of either recombinant human (rh) G-CSF or rhGM-CSF
      alone in a dose-dependent fashion. In contrast to the response of eosinophils to
      HBEC-CM, steroid treatment did not prevent the increase in neutrophil survival
      induced by HBEC-CM. In summary, we show that bronchial epithelial cells markedly
      increase the survival of human neutrophils in vitro via the release of G-CSF and
      GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384584
TI  - Plant membrane transport.
AB  - Recent developments in plant membrane transport, particularly concerning the
      vacuolar and plasma membranes, have increased our understanding of molecular
      aspects of primary pumps, carrier systems and ion channels.

PMID- 1384585
TI  - Modulation of acute phase protein synthesis in cultured rat hepatocytes by human
      recombinant hepatocyte growth factor.
AB  - Human recombinant hepatocyte growth factor (HGF) added to primary cultures of rat
      hepatocytes stimulates synthesis of some acute phase proteins, especially alpha-2
      macroglobulin. As indicated by changes in mRNA abundance HGF increases alpha-2
      macroglobulin production at the pretranslational level. Interleukin-6, the main
      acute-phase cytokine, does not show synergy with HGF in enhancing synthesis of
      alpha-2-macroglobulin, and inhibits HGF-induced DNA-synthesis. On the other hand,
      dexamethasone potentiates the effects of HGF on synthesis of DNA and acute phase
      proteins by cultured rat hepatocytes.

PMID- 1384586
TI  - Acidic fibroblast growth factor (aFGF) in developing normal and dystrophic (mdx)
      mouse muscles. Distribution in degenerating and regenerating mdx myofibres.
AB  - Affinity purified polyclonal antibodies directed against human recombinant acidic
      FGF (aFGF), were used in immunofluorescence studies to localize this growth
      factor in several normal and dystrophic (mdx) mouse skeletal muscles. The
      expression of aFGF was detected throughout the life of both the control and mdx
      mice. In striated muscles, examined up to 3 weeks postnatal, aFGF was localized
      around the myofibres and this pattern was consistent in both mdx and the normal
      counterpart strain. However, the intensity of the signal was much stronger in the
      mdx strain. In mdx mouse skeletal muscles, examined during the acute phase of
      degeneration and regeneration (3-14 weeks) aFGF was localized around the
      myofibres, in approximately 60% of the nuclei of newly formed or regenerated
      myofibres and also in the pockets of necrosis which represented actively
      degenerating myofibres. In normal mouse skeletal muscles, studied over the same
      period, the antibodies localized aFGF mainly to the periphery of the muscle
      fibres. The augmentation of aFGF observed by immunofluorescence in mdx mouse
      muscles was confirmed by enzyme immunoassay (EIA) analysis of the same muscles
      over the same period of time. The data from the EIA indicated a 3.5-fold increase
      in aFGF in mdx as compared to normal muscles at 3 weeks, and an approximate 26
      fold increase during the period of active degeneration-regeneration. This
      increased concentration of aFGF noted in the mdx muscles suggests that this
      endogenous aFGF may participate in the high level of regenerative activity
      observed in mdx mouse.

PMID- 1384587
TI  - Comparison of bioanalytical determinations of Iloprost, a chemically stable PGI2
      mimetic, by conventional radioimmunoassay (RIA) and scintillation proximity assay
      (SPA).
AB  - The scintillation proximity assay is a novel variant of classical
      radioimmunoassay. It can be performed as a single tube measurement because the
      separation of bound and unbound tracer fraction is avoided. In principle,
      microbeads are coated with anti-species antibodies that can couple with the
      respective antiserum used for RIA. By means of special cores, light emission
      takes place if labelled, antiserum-bound tracer is coupled to the anti-species
      antibody on the fluomicrosphere surface. In the present report, the novel assay
      was compared to a validated RIA for the bioanalysis of the PGI2 mimetic,
      Iloprost. Extraction recovery of Iloprost was approximately 90% at pH less than
      or equal to 4. The detection limit of the novel assay was 2-4 pg/sample,
      corresponding to 10-20 pg/ml plasma (if 0.2 ml plasma was used). Coefficients of
      variations were 9, 7 and 6% (within-day, n = 5) and 30, 11 and 10% (day-to-day, n
      = 10) at 50, 100 and 200 pg/ml. RIA and SPA levels of Iloprost measured in human
      plasma samples (n = 428) were similar. The SPA method exhibits both a similar
      specificity and detection limit to RIA and will be used for further analyses.

PMID- 1384588
TI  - Small cell prostate cancer with bone marrow invasion--a case report.

PMID- 1384589
TI  - Cytolytic toxins.

PMID- 1384590
TI  - Ion channel and membrane translocation of diphtheria toxin.
AB  - Diphtheria toxin is the best studied member of a family of bacterial protein
      toxins which act inside cells. To reach their cytoplasmic targets, these toxins,
      which include tetanus and botulinum neurotoxins and anthrax toxin, have to cross
      the hydrophobic membrane barrier. All of them have been shown to form ion
      channels across planar lipid bilayer and, in the case of diphtheria toxin, also
      in the plasma membrane of cells. A relation between the ion channel and the
      process of membrane translocation has been suggested and two different models
      have been put forward to account for these phenomena. The two models are
      discussed on the basis of the available experimental evidence and in terms of the
      focal points of difference, amenable to further experimental investigations.

PMID- 1384591
TI  - Computer modelling of the transmembrane channel formed by a CNBr peptide of
      diphtheria toxin B fragment.
AB  - Diphtheria toxin (DT) forms transmembrane, voltage-dependent channels in a planar
      lipid bilayer. Channels with similar characteristics were obtained with CB1, a
      cyanogen bromide peptide of diphtheria toxin B fragment (DTB) (res 340-459).
      Tryptophan 398 is in interaction with the hydrophobic core of the lipid bilayer.
      Using the Eisenberg method in association with the Shiffer-Edmunson wheel
      representation, we have identified two amphipathic alpha-helices within CB1 (res
      346-364 and 389-406) that could be involved in the interaction with lipids.
      Bearing this information in mind, we are providing a model for the structure of
      the CB1 channel.

PMID- 1384592
TI  - Polypeptide cytolytic toxins from sea anemones (Actiniaria).
AB  - Biochemical and biological properties of 30 cytolytic polypeptide toxins isolated
      from 18 species of sea anemones (Actiniaria) are presented and classified into
      three groups according to their molecular mass, isoelectric points and the
      molecular mechanism of action. Phospholipase A2-like toxins (30 kDa) from
      Aiptasia pallida are dissimilar to acidic metridiolysin (80 kDa) from Metridium
      senile and the group of about 27 predominantly basic toxins, having a molecular
      mass of 16-20 or 10 kDa, inhibited by sphingomyelin. They are lethal for both
      invertebrates and vertebrates, cardiotoxic, cytolytic and cytotoxic.
      Pharmacological activities, cytotoxic and cytolytic properties are mediated, at
      least in part, by forming pores in lipid membranes. Channels, 1-2 nm in diameter,
      formed in planar lipid membranes are cation selective and rectified. The
      mechanisms and some characteristics of ion channel formation by the toxins in the
      cells as well as in artificial lipid membranes are summarized and discussed in
      view of the structure-function studies of the toxins. Putative biological roles
      of toxins, based on their channel-forming activity, in the capture and killing of
      prey, digestion, repelling of predators and intraspecific spatial competition are
      suggested.

PMID- 1384593
TI  - The channel-forming toxin aerolysin.
AB  - Aeromonas sp. secrete a precursor of the cytolytic protein aerolysin into the
      culture medium, where it is activated by proteolytic removal of a C-terminal
      fragment. Activation can be achieved by a variety of mammalian proteases as well
      as by proteases released by the bacteria itself. Activated toxin binds with high
      affinity to the transmembrane protein glycophorin on the surface of eucaryotic
      cells. Binding is followed by oligomerization and the formation of transmembrane
      channels, leading to cell death. Using chemical modification and site-directed
      mutagenesis, we have identified regions of the molecule which are important in
      transfer across the outer membrane of the bacteria, and in proteolytic
      activation, binding, and oligomerization. A preliminary electron density map of
      proaerolysin crystals indicates that the protein is organized into three domains.
      Analysis of two-dimensional crystals of aerolysin suggests that the oligomeric
      form of the protein is heptameric.

PMID- 1384594
TI  - Alpha-latrotoxin: preparation and effects on calcium fluxes.
AB  - A toxin that causes a massive presynaptic activation of transmitter release from
      nerve terminals is alpha-latrotoxin, isolated from Latrodectus tredecimguttatus
      spider venom. This toxin has been highly purified, utilizing as a biological
      assay a toxin-dependent increase in 45Ca(2+)-accumulation by PC12 cells. The
      purification protocol includes an ion-exchange step and a gel-filtration column,
      by fast-flow liquid chromatography. The resulting toxin is a polypeptide of about
      125 kDa in molecular mass. At nmol concentrations it specifically activates
      calcium influx and transmitter secretion after interacting with neuronal
      acceptors of the presynaptic membrane. The inhibitory effect of trivalent ions
      (which may develop as degradation product of 45Ca2+) on toxin-dependent calcium
      accumulation by PC12 cells is described. The results obtained suggest that
      calcium fluxes directly involved in the neurosecretory event, may occur through
      newly formed toxin-dependent channels.

PMID- 1384595
TI  - Membrane-modifying properties of the pore-forming peptaibols saturnisporin SA IV
      and harzianin HA V.
AB  - Harzianin HA V and saturnisporin SA IV are alpha-amino isobutyric-containing
      peptides with 18- and 20-residue chain length, respectively. They were isolated
      from in vitro cultures of Trichoderma species and their sequences were determined
      by the combined use of positive ion FAB mass spectrometry and NMR. In organic
      solvent solution, both peptides exhibited the same predominant alpha-helical
      secondary structure including a hinge at the level of the central Pro residue, as
      deduced from NMR data. Their interaction with neutral phospholipid bilayers was
      shown to induce leakage of the material entrapped in small unilamellar vesicles
      composed of egg phosphatidylcholine/cholesterol (7/3). When incorporated into
      neutral planar lipid bilayers, they promoted voltage-gated channels. The
      concentration- and voltage-dependences of the ionic conductances induced by these
      peptides were studied in macroscopic current-voltage experiments. Single-channel
      measurements showed that whilst SA IV developed non-integral multi-open states
      similar to those induced by alamethicins, but with faster kinetics, the shorter
      analogue, HA V promoted much smaller-sized conducting aggregates in agreement
      with macroscopic conductance data.

PMID- 1384596
TI  - Structural features of the pore formed by Staphylococcus aureus alpha-toxin
      inferred from chemical modification and primary structure analysis.
AB  - Staphylococcus aureus alpha-toxin makes cells and model membranes permeable to
      ions and uncharged molecules by opening oligomeric pores of uniform size. Its
      primary sequence reveals peculiar features which give some hints on the structure
      of the pore. A flexible region separating the toxin into two halves, several
      amphiphilic beta-strands and two amphiphilic alpha-helices long enough to span
      the hydrophobic core of the lipid bilayer are predicted. In analogy to bacterial
      porins, we propose that the inner walls of the pore are, at least in part, built
      by an amphiphilic beta-barrel. The model is consistent with circular dichroism
      data and with the electrophysiological properties of the pore. Functional
      information on this toxin were obtained by chemical modification of its four
      histidine residues. Specific carbethoxylation suggested they have different
      roles: one is required for specific receptor binding, one for oligomerisation and
      two for unspecific lipid binding. A tentative assignment of each histidine to its
      specific role is done on the basis of the structural predictions. A functionally
      related hemolysin, Aeromonas hydrophyla aerolysin, reveals remarkably similar
      features including the presence and location of histidines involved in receptor
      binding and oligomerisation.

PMID- 1384597
TI  - Haemolysin of Escherichia coli: comparison of pore-forming properties between
      chromosome and plasmid-encoded haemolysins.
AB  - Lipid bilayer experiments were performed with chromosome-encoded haemolysin of
      Escherichia coli. The addition of the toxin to the aqueous phase bathing lipid
      bilayer membranes of asolectin resulted in the formation of transient ion
      permeable channels with two states at small transmembrane voltages. One is a
      prestate (single-channel conductance 40 pS in 0.15 M KCl) of the open state,
      which had a single-channel conductance of 420 pS in 0.15 M KCl and a mean
      lifetime of 30 s. Membranes formed of pure lipids were rather inactive targets
      for this haemolysin. Experiments with different salts suggested that the
      haemolysin channel was highly cation-selective at neutral pH. The mobility
      sequence of the cations in the channel was similar if not identical to their
      mobility sequence in the aqueous phase. The single-channel data were consistent
      with a wide, water-filled channel with an estimated minimal diameter of about 1
      nm. The pore-forming properties of chromosome-encoded haemolysin were compared
      with those of plasmid-encoded haemolysin. Both toxins share common features,
      oligomerize probably to form pores in lipid bilayer membranes. Both types of
      haemolysin channels have similar properties but different lifetimes.

PMID- 1384598
TI  - Physical characterization of the pore forming cytolysine from Gardnerella
      vaginalis.
AB  - The cytolytic toxin (CTox) produced by Gardnerella vaginalis is able to form
      voltage-dependent cationic channels when incorporated in lipid membranes (Moran
      et al. (1991) FEBS Lett. 283, 317-320). Osmotic protection experiments show that
      toxin incorporated in human erythrocytes forms pores between 18 A and 28 A in
      diameter. A hypothesis of pore formation as a primary event to produce cytolysis
      is proposed. The CTox activity increases when cells are depolarized by increasing
      the extracellular K+ concentration, probably reflecting the voltage dependent
      character of CTox formed channels. The cytolytic effect of the toxin was
      prevented by low temperatures and was a function of the extracellular Ca2+
      concentration, suggesting a Ca2+ influx as part of the lytic mechanism. Binding
      of CTox to erythrocytes was dependent on external Ca2+ and was less temperature
      dependent. Dose-response analysis suggests cooperativity of the toxin for the
      lytic activity, although no direct evidence of oligomerization has been found.

PMID- 1384599
TI  - Dynamic properties of the colicin E1 ion channel.
AB  - The mechanism of channel formation and action of channel-forming colicins is a
      paradigm for the study of dynamic aspects of membrane-protein interactions. The
      following experimental results concerning interaction of the colicin E1 channel
      domain with target membranes, in vitro and in vivo, are discussed: (1) the nature
      of the translocation-competent state of the channel-forming domain; (2) unfolding
      of the colicin channel peptide during in vitro binding and anchoring of the
      channel to liposome membranes at acidic pH; (3) reversal of channel peptide
      binding to liposomes by an alkaline-directed pH shift; (4) voltage-driven
      translocation and gating of the ion channel, discussed in the context of a four
      helix model for a monomeric channel; (5) rescue of colicin-treated cells by high
      levels of external K+; (6) trypsin rescue of cells depolarized by the colicin ion
      channel; and (7) interaction of the channel domain with its immunity protein.

PMID- 1384600
TI  - Membrane damage: common mechanisms of induction and prevention.
AB  - Common features in the induction of pores by various agents are as follows:
      induction is stochastic and progressive; damage by different agents is often
      synergistic and limited. The prevention of membrane damage is affected by
      trivalent and divalent cations, by low pH, by low ionic strength and by high
      osmotic pressure. The inhibitory role of protons and divalent cations is
      considered in greater detail: pore-forming agents can be classified into two
      groups: channels across planar lipid bilayers induced by the first group display
      voltage-sensitive, reversible inhibition by divalent cations; channels of the
      second group show voltage-insensitive, irreversible inhibition by divalent
      cations. A search for the ligands to which divalent cations and protons bind has
      proved elusive. Comparison with the phenomenon of 'surface conductance' through
      narrow apertures, that is manifest in the absence of any pore-forming agent, may
      prove fruitful.

PMID- 1384601
TI  - A simple method for the determination of the pore radius of ion channels in
      planar lipid bilayer membranes.
AB  - A new method of pore size determination is presented. The results of applying
      this simple method to ion channels formed by staphylococcal alpha-toxin and its N
      terminal fragment as well as to cholera toxin channels are shown. The advantages
      and the difficulties of this method are discussed. It was found that (i) the
      mobility of ions in solutions depends only on the percentage of concentration of
      added non-electrolytes and practically not on their chemical nature (sugars or
      polyglycols) and molecular size; (ii) the proportional change of both ion channel
      conductance and bulk solution conductivity by low M. nonelectrolytes may be used
      as an indication of a diffusion mechanism of ion transport through channels;
      (iii) the slope of the dependence of the ion channel conductance on the bulk
      conductivity of solutions containing different concentrations of non-electrolyte
      is a good measure of channel permeability for non-electrolytes.

PMID- 1384602
TI  - Recombinant acellular pertussis vaccine--from the laboratory to the clinic:
      improving the quality of the immune response.
AB  - Vaccination is the most effective way to prevent infectious diseases. Recombinant
      DNA technologies have provided powerful new tools to develop vaccines that were
      previously impossible or difficult to make, and to improve the vaccines that were
      already available but had been developed using old technology. In the case of
      whooping cough, an effective vaccine (composed of killed bacterial cells) is
      available, but its use is controversial because of the many side effects that
      have been associated with it. An improved vaccine against this disease should
      contain pertussis toxin, a molecule that needs to be detoxified in order to be
      included in the vaccine. Classical methods of detoxification, such as
      formaldehyde treatment have been used to inactivate this toxin. We have used
      recombinant DNA technologies to clone the pertussis toxin gene, express it in
      bacteria, map the B and T cell epitopes of the molecule, and to identify the
      amino acids that are important for enzymatic activity and toxicity. Finally, we
      have used this information to mutate the gene in the chromosome of Bordetella
      pertussis in order to obtain a strain that produces a molecule that is already
      non-toxic. This genetically inactivated pertussis toxin was tested extensively in
      animal models and clinical trials and was found to induce an immune response that
      is superior in quality and quantity to that induced by the vaccines produced by
      conventional technologies.

PMID- 1384603
TI  - Induction of various cytokines in mice and activation of the complement system in
      rats as a part of the mechanism of action of the Corynebacterium granulosum
      derived P40 immunomodulator.
AB  - The capacity of the Corynebacterium granulosum-derived P40 immunomodulator to
      induce in mice the formation of various cytokines IFN, IL-1, IL-2, alpha-TNF as
      well as to activate the complement system in rats was investigated. The results
      showed that P40 injected by the intravenous route was capable of inducing the
      formation of all four cytokines. High levels of IFN were measured 2 h after P40
      stimulation and were still present at 24 h. The kinetic study of IL-1, IL-2 and
      alpha-TNF induction showed that it was a biphasic phenomenon. The patterns of IL
      1 and alpha-TNF induction were quite comparable, whereas the release of IL-2 was
      delayed with respect to that of IL-1 and alpha-TNF. Oral administration of P40 to
      rats strongly activated the alternative pathway of the complement system. It was
      concluded that most of the non-specific effects of P40 on the immune system are
      likely to be mediated by its capacity to induce cytokine formation and to
      activate the complement system.

PMID- 1384604
TI  - Vitronectin binding by Helicobacter pylori.
AB  - Vitronectin, a serum and extracellular matrix protein involved in immunological
      reactions, interacts with Helicobacter pylori strains. Of the 20 H. pylori
      strains tested three strains bound more than 50% of the vitronectin added, five
      strains bound 25-40%, nine strains bound 10-20% and three strains bound 5-8%
      vitronectin. Two strains, one with high- and one with low-binding properties,
      were selected for further characterization of 125I-vitronectin binding. Binding
      to the urea-activated 125I-labelled vitronectin was fast, saturable and
      reversible when an excess of unlabelled vitronectin was added to the bacteria
      with bound 125I-vitronectin. The binding was heat- and protease-sensitive,
      suggesting that the binding was mediated by bacterial cell-surface proteins.
      Since components such as fetuin and orosomucoid but not asialofetuin inhibited
      the binding, sialic-acid specific proteins, related to H. pylori sialic-acid
      specific haemagglutinins, were probably involved.

PMID- 1384605
TI  - [Disorders of cardiac rhythm and conductivity after radical correction of
      tetralogy of Fallot in young children].
AB  - Analysis of electrocardiograms in 55 children who underwent operation for
      Fallot's tetralogy at early age showed that the frequency and severity of
      postoperative disorders of rhythm and conductivity were determined by the degree
      of trauma inflicted by the used surgical techniques. Data obtained in the early
      and late-term postoperative periods confirm the expediency of performing surgical
      correction of the anomaly as early as possible by means of surgical methods which
      cause little injury. The results of the study are recommended for use in choosing
      the surgical tactics, for functional appraisal of the operative results.

PMID- 1384606
TI  - Distribution of CGRP, substance P, VIP and somatostatin immunoreactive nerve
      fibers in the internal gills of larvae of the bullfrog, Rana catesbeiana.
AB  - CGRP, substance P (SP), VIP and somatostatin were demonstrated in the internal
      gills of larval bullfrogs using the immunohistochemical peroxidase-antiperoxidase
      method. Three groups of immunoreactive fibers were distinguished by their
      distribution area. The first group includes CGRP, SP and VIP immunoreactive
      fibers running in the connective tissue of the gill tufts. These fibers were
      associated with the capillaries. Some CGRP fibers were distributed similarly to
      SP fibers, and the density of VIP immunoreactive fibers was low. The second group
      includes CGRP, SP, VIP and somatostatin fibers distributed in the connective
      tissue surrounding the ceratobranchialia. The third group includes CGRP, SP and
      somatostatin fibers located in the branchial muscle. Their terminals appeared to
      be neuromuscular junctions. No immunoreactivity of leu- or met-enkephalins was
      found in the internal gills. From these findings, the first group of fibers is
      presumed to be involved in modulating ion transport of the internal gills. The
      second group of fibers except for the somatostatin fibers is thought to be
      continuations of the first group of fibers. The third group of fibers may
      possibly be involved in the modulation of transmissions at the neuromuscular
      junction. It is unclear whether somatostatin terminals are also involved in this.

PMID- 1384607
TI  - lacZ transduced human breast cancer xenografts as an in vivo model for the study
      of invasion and metastasis.
AB  - A number of human cancer cell lines have been described as being invasive and
      metastatic in immune incompetent animals. However, it is difficult to assess
      metastatic spread of a subcutaneously injected or inoculated cell line, since an
      exact detection of all microfoci of human tumour cells in the animals by usual
      histological procedures would require extensive sectioning of the whole animal.
      To overcome this problem, we transduced human breast cancer cells with a
      replication-defective Moloney murine leukaemia retroviral vector (M-MuLV)
      containing both neoR (neomycin resistance) and lacZ genes. The resulting cell
      lines were selected for antibiotic (G418) resistance, and cell-sorted for lacZ
      expression. lacZ continued to be expressed in cultured cells for at least 20
      passages without further G418 selection. The lacZ gene codes for beta-D
      galactosidase, and cells expressing this gene stain blue with the chromogenic
      substrate X-gal. The lacZ-expressing cells retained the pre-transduction ability
      to traverse Matrigel in vitro, to form subcutaneous tumours in nude mice, and to
      grow invasively with the formation of metastases. X-gal staining showed high
      specificity, staining the tumour cells but not the surrounding mouse tissue on
      either whole tissue blocks or histological sections. The staining procedure was
      highly sensitive, allowing detection of microfoci of human cancer cells, and
      quantitative estimation of the metastatic capacity of the cells. These results
      indicate that lacZ transduction of human tumour cells is a powerful means of
      studying human cancer cell invasion and metastases in vivo.

PMID- 1384608
TI  - Cigarette smoking is a risk factor for bleomycin-induced pulmonary toxicity.

PMID- 1384609
TI  - The role of three cisplatin-based chemotherapy regimens in the treatment of
      advanced non-small cell lung cancer.

PMID- 1384610
TI  - [The effects of cholestyramine on pancreatic secretion].
AB  - The objective was to evaluate the effect of biliary salt depletion on morphology
      and function of the exocrine pancreas. Cholestyramine (15 g/day) was given during
      fifteen days to male Wistar rats in order to evaluate changes in pancreas weight
      as well as in enzymatic content of pancreatic tissue and duodenal juice (amylase,
      lipase and trypsinogen); in duodenal juice, bile salt concentration was also
      measured; Moreover ultrastructure of the exocrine pancreas was studied. Our
      results show an increase in pancreas weight in rats treated with cholestyramine,
      with a significant increase of amylase (p < 0.05) and trypsinogen in pancreatic
      tissue (p < 0.01), and of lipase in duodenal juice (p < 0.05). Ultrastructural
      changes were absent. It is concluded that cholestyramine, probably through a bile
      salt depletion, stimulates pancreatic function and growth, as well as lipase
      secretion.

PMID- 1384611
TI  - Liver and plasma copper concentrations in rats fed diets containing various
      proteins.
AB  - The question was addressed whether the type of dietary protein influences copper
      (Cu) concentrations in liver and plasma of rats. For this purpose, weanling
      female rats were fed diets containing as the sole source of protein either
      soybean protein, casein, amino acid mixtures simulating soybean protein or
      casein, lactalbumin, ovalbumin, or herring meal. The diets were balanced for
      residual Cu in the protein preparations. The type of protein and the composition
      of the amino acid mixture did not differentially influence liver Cu
      concentrations. Liver Cu was significantly lowered after feeding the amino acid
      mixtures when compared with the intact proteins. Plasma Cu concentrations were
      not affected by the type of protein in the diet.

PMID- 1384612
TI  - Accumulation of vanadium during embryogenesis in the vanadium-rich ascidian,
      Ascidia gemmata.
AB  - It is a remarkable and previously unrecognized fact that ascidians, which are
      known to contain high levels of vanadium in their blood cells, begin to
      accumulate vanadium during embryogenesis. This study revealed that the
      accumulation starts quite dramatically 2 wk after fertilization, and 2 mo later,
      the amount of vanadium in larvae is 600,000 times higher than that in the
      unfertilized egg. These results were obtained by neutron activation analysis, a
      highly sensitive method for determining levels of vanadium, in the Ascidia
      gemmata, the ascidian that contains the highest known levels of vanadium and
      accumulates vanadium at 150 mM in its blood cells, a concentration that
      corresponds to 4,000,000 times the concentration in seawater.

PMID- 1384613
TI  - The effect of malathion, diazinon, and various concentrations of zinc, copper,
      nickel, lead, iron, and mercury on fish.
AB  - Acute and chronic toxicity tests for malathion, diazinon, copper (Cu), mercury
      (Hg), lead (Pb), zinc (Zn), nickel (Ni), and iron (Fe) were conducted.
      Mortalities of Barilius vagra and Cyprinus carpio (common carp) were variable but
      LC50-96 hr were similar for pesticides. Adult B. vagra seem to be more sensitive
      to malathion than juvenile carp. Both juvenile carp and adult B. vagra were
      extremely sensitive to diazinon. Long-term exposure to pesticides modified
      morphology and behavior. The LC50-96 values for Cu, Hg, and Pb were 0.3, 0.16,
      and 0.44, respectively, for smaller fish and 1.0, 0.77, and 1.33, respectively,
      for larger fish. Replicate LC50 values for Zn, Ni, and Fe were somewhat variable,
      and for these metals, the size of the fish seemed to affect response because LC50
      values increased as fish size increased. Copper, Pb, Zn, and Fe residues
      following exposure to sublethal concentrations of these metals for 15 d were
      significantly greater in whole juvenile common carp than in controls.

PMID- 1384615
TI  - Proton-induced X-ray emission analysis of atherosclerotic plaques of the carotid
      bifurcation.
AB  - The trace elements of both calcified atherosclerotic plaques and plaque-free
      vessel walls of the carotid bifurcation from 31 autopsies were investigated using
      the proton-induced X-ray emission (PIXE) method. The trace elements studied were
      phosphorus (P), calcium (Ca), chrome (Cr), iron (Fe), copper (Cu), zinc (Zn),
      lead (Pb), selenium (Se), bromine (Br), strontium (Sr), and rubidium (Rb). All
      samples contained Fe and Zn. Mercury (Hg) was not detected in any of the samples
      studied. All plaque-free samples contained Cu and almost all Br and Ca, none Sr.
      All calcified atherosclerotic plaques contained Ca and almost all Br and Sr. The
      relative levels of Ca were higher in the calcified plaques than in the plaque
      free vessel walls. The relative value of Ca in calcified and uncalcified samples
      was greatest in the group who had died because of cardiovascular disorders and
      smallest in the group who had died from other causes. There was a strong positive
      correlation between the Ca and Sr of the plaque samples and between the P and Br
      of the plaque-free samples.

PMID- 1384616
TI  - Sex-linked, androgen-dependent differences in renal retention of
      trimethylselenonium ions.
AB  - The metabolism of trimethylselenonium ions (TMSe) was studied in male and female
      rats during maturation. Selenium (Se) retention in the whole body as well as in
      organs was found to be significantly higher in male rats than in female a few
      hours after parenteral administration of TMSe. The pronounced Se accumulation was
      observed in male kidneys. This sex-linked difference was dependent on the
      presence of gonads and started to be manifested with sexual maturation during the
      third decade of postnatal life. The effects of steroid hormones on the retention
      of Se from TMSe were examined in female and castrated male rats. The results
      indicate that TMSe metabolism in rat kidneys may be influenced by androgen
      steroids.

PMID- 1384614
TI  - Changes in plasma zinc, copper, iron, and hepatic metallothionein in adjuvant
      induced arthritis treated with cyclosporin.
AB  - The early changes in hepatic metallothionein (MT) and plasma zinc (Zn), copper
      (Cu), and iron (Fe) were investigated during the induction of adjuvant (AJ)
      arthritis in rats in conjunction with cyclosporin (CsA) treatment. Plasma Zn
      decreased after AJ injection (60% of control values at 8 h), and this was
      associated with a 4.5-fold increase in hepatic MT at 8 h. Plasma Zn was lowest at
      16 h (40% of control), whereas hepatic MT concentrations increased to a maximum
      of 20-fold at 16 h. Changes in plasma Fe paralleled those of Zn, whereas plasma
      Cu levels were increased. Plasma metal and hepatic MT concentrations returned
      toward normal from d 1-7. At d 14, when marked paw swelling was apparent, hepatic
      MT and plasma Cu were again increased and plasma Zn decreased. Administration of
      CsA decreased MT induction in rats injected with AJ and also caused a marked
      recovery in plasma Zn and Fe levels. These changes were small but significant
      even in the early stages (up to 24 h) after AJ injection and were followed by a
      sustained improvement in all parameters, corresponding to the nonappearance of
      clinical arthropathy in CsA-treated rats. TNF-alpha and IL-6 production by
      peritoneal macrophages isolated from AJ-injected rats was significantly decreased
      by CsA treatment at d 7 and 14. The inhibition of hepatic MT induction during
      acute and chronic inflammation by cyclosporin emphasizes the role of the immune
      system in altered metal homeostasis in inflammation.

PMID- 1384617
TI  - Effect of dietary fluoride on selenite toxicity in the rat.
AB  - Three factorial experiments were conducted to determine if high dietary fluoride
      (F) would inhibit selenite toxicity in rats. Initially, three levels of selenite
      (0.05, 3, and 5 mg/kg diet) were matched against three levels of F (2, 75, and
      150 mg/kg diet). Fluoride failed to prevent the depressive effect of selenite on
      8-wk food intake and body wt gain. Selenium (Se) concentration of plasma and
      kidney and enzymatic activity of whole blood glutathione peroxidase (GSH-Px) were
      also unaffected by F. Liver Se concentration, however, was slightly (12%) but
      significantly (p < 0.025) reduced when the highest F and Se levels were combined.
      Fluoride (150 mg/kg) appeared to reduce liver selenite toxicity (5 mg/kg).
      Therefore, further study focused on liver histology with treatments that
      eliminated the middle levels of selenite and F. Fluoride prevented the hepatic
      necrosis seen in selenite-toxic rats. Similar histological lesions were not
      observed for kidney or heart. Fluoride partially (26%) but significantly (p <
      0.025) reduced thiobarbituric-reactive substances in selenite-toxic rats, but
      there was no F effect on intracellular distribution of liver Se, glutathione
      levels in liver and kidney, or on liver xanthine oxidase activity. Overall, the
      protective effect of F on selenite toxicity appears to be confined to liver
      pathology. The exact mechanism for this effect, however, remains unclear.

PMID- 1384618
TI  - Modifying effect of iron on lead-induced clastogenicity in mouse bone marrow
      cells.
AB  - Essential trace elements such as iron (Fe) are known to interact with
      nonessential metals like lead (Pb), influencing its metabolism. Ferric chloride
      and lead nitrate were administered intraperitoneally to Swiss albino mice Mus
      musculus singly and successively, with or without a time gap of 1 h, to study the
      degree of protection, if any, afforded by iron against the clastogenic effects
      induced by Pb in bone marrow cells. A decrease in the frequency of lead-induced
      chromosomal aberrations was observed when Fe was given together with or prior to
      Pb administration.

PMID- 1384619
TI  - The relationship between the rate of chelator-induced zinc efflux from
      erythrocytes and zinc status.
AB  - The rate of zinc (Zn) release from rat erythrocytes incubated in buffers
      containing a variety of chelators was measured. Only o-phenanthroline, 8
      hydroxyquinoline-5-sulfonate, and EDTA caused detectable Zn release. The
      relationship between the rate of this release in the presence of o-phenanthroline
      and Zn status was determined in rats. Rats were fed one of the following: a
      modified AIN-76 diet providing 46 mumol (3 mg) Zn per kg of diet, a pair-fed diet
      providing 459 mumol (30 mg)/kg, or the previous diet fed ad lib. Animals were
      sacrificed at 2-wk intervals for 12 wk, and the Zn efflux rate, plasma, liver,
      and femur Zn concentrations were determined. The efflux rate was lower in
      erythrocytes taken from the rats fed the low-Zn diet. The efflux rate was also
      well correlated with femur Zn (r = 0.509, n = 98, p < 0.0001). A poorer
      correlation was observed with plasma Zn in the rats. Correlations also were
      determined between efflux rates and plasma Zn levels in human subjects. There was
      a significant correlation only in the males. In was concluded that the Zn efflux
      rate from erythrocytes incubated in the presence of o-phenanthroline is related
      to Zn status but is not sensitive enough to be a useful index of this status.

PMID- 1384620
TI  - Evidence for dietary essentiality of lithium in the rat.
AB  - The purpose of this study was to determine the dietary essentiality of lithium
      (Li) in rats. In three experiments, two types of diets were fed during growth,
      reproduction, and lactation. In the first experiment, dams were maintained on a
      corn-based diet containing 2 ng or 500 ng (controls) Li/g through five successive
      periods of pregnancy and lactation. The offspring of dams fed the low-Li diet had
      significantly lower weaning weights (p = 0.011), and the percent weaned was lower
      (p = 0.094) than that of controls. In the second experiment, rats were maintained
      through three generations on a rice-based diet containing 0.6 ng Li/g, or the
      control (500 ng/g) diet. There was a significant effect of Li level on litter
      size (p = 0.017) and litter wt at birth (p = 0.006) in the third generation. The
      overall effect through three generations on litter wt at birth approaches
      statistical significance (p = 0.086). In the third experiment, third-generation
      rats were continued on the respective rice-based diets with three levels of
      dietary sodium, the normal level, one-half, and four times that level. The litter
      size and birth wt were significantly lower (p = 0.0030 and 0.0038, respectively)
      among the low-Li dams that consumed the normal and high-sodium levels compared to
      those that consumed the low-sodium diets. The interaction of Li and sodium as
      regards litter wt at birth approached significance (p = 0.083). Various tissues
      of the rats in the third experiment were analyzed for Li. It seems likely that Li
      exerts an essential nutrient role for the rat.

PMID- 1384623
TI  - Iron: A Marginally Available Nutrient. Symposium proceedings. Wageningen, The
      Netherlands.

PMID- 1384621
TI  - The role of selenium in thyroid hormone metabolism and effects of selenium
      deficiency on thyroid hormone and iodine metabolism.
AB  - Selenium deficiency impairs thyroid hormone metabolism by inhibiting the
      synthesis and activity of the iodothyronine deiodinases, which convert thyroxine
      (T4) to the more metabolically active 3,3'-5 triiodothyronine (T3). Hepatic type
      I iodothyronine deiodinase, identified in partially purified cell fractions using
      affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also
      labeled with 75Se by in vivo treatment of rats with 75Se-Na2SeO3. Thus, the type
      I iodothyronine 5'-deiodinase is a selenoenzyme. In rats, concurrent selenium and
      iodine deficiency produces greater increases in thyroid weight and plasma
      thyrotrophin than iodine deficiency alone. These results indicate that a
      concurrent selenium deficiency could be a major determinant of the severity of
      iodine deficiency.

PMID- 1384624
TI  - The physiology of iron, transferrin, and ferritin.
AB  - The role of transferrin in iron metabolism is evaluated, both with regard to iron
      uptake by transferrin and to iron uptake from transferrin by different cells. The
      heterogeneity of serum transferrin is described and the implications of the
      heterogeneity are discussed. The composition of ferritin is given and the value
      of serum ferritins are discussed.

PMID- 1384622
TI  - Significance of iron bioavailability for iron recommendations.
AB  - Recently, recommended dietary allowances (RDA) have been formulated by the Dutch
      Nutrition Council for minerals and trace elements, including iron (Fe). For some
      population groups in the Netherlands, it is questionable whether they easily meet
      the Fe recommendation. An increase in Fe intake is not always possible, but
      "manipulation" of Fe bioavailability ultimately may result in better Fe
      utilization. Various factors are known to affect Fe bioavailability. Generally,
      much attention is paid to diet-related factors, such as inhibitors and enhancers
      of Fe availability for absorption. Factors such as pH, oxidation potential,
      structure of food, and time of digestion often are overlooked. Of the diet
      related factors, heme Fe and ascorbic acid have a strong positive effect on Fe
      availability for absorption, whereas oxalate and polyphenols seem to be strong
      inhibitors of Fe availability. Because of the many interactions that may occur
      simultaneously, the net effect of the various combined factors in a meal is not
      equal to the sum of the individual factors.

PMID- 1384625
TI  - Iron requirements. Comments on methods and some crucial concepts in iron
      nutrition.
AB  - Absorbed iron (Fe) requirements are partly recalculated based on new figures for
      Fe requirements in menstruating women. The new higher figures were obtained by
      including in the calculation of the total requirements the effect of variations
      in hemoglobin concentration, which influences the variation in menstrual Fe
      losses and the variation in basal Fe losses. Higher figures were also found for
      menstruating teenage girls. Dietary iron requirements were also recalculated
      based on a critical examination of data available allowing estimations of
      bioavailability of the dietary iron in Western-type diets. In borderline Fe
      deficient subjects, with optimal hemoglobin levels but no iron stores, the 95th
      percentile range for the bioavailability was estimated to 14-16% of the fraction
      of the dietary Fe that is potentially available for absorption (correction for
      partially available fortification Fe).

PMID- 1384626
TI  - Comparison of cytosolic products formed in rat liver in response to parenteral
      and dietary iron loading.
AB  - Two different methods were used to create a situation of iron (Fe) overload in
      rats. One group of rats received Fe dextran, and another group of rats received a
      carbonyl Fe-enriched diet. The ferritins present in the liver cytosol of these
      rats were isolated and compared. From each group, two cytosolic products were
      isolated with the use of ultracentrifugation: a cytosolic ferritin fraction (CF)
      and a (slower sedimenting) light ferritin fraction (CLF). There were no
      differences with respect to the protein coat (subunit composition and amino acid
      analysis). Analysis of the Fe core revealed that the two CF fractions were
      similar, whereas the two CLF fractions differed with respect to their Fe content
      and to the packing of their cores. The carbonyl CLF product contained less Fe
      atoms/molecule, which, moreover, seemed to be packed in a less compact way.

PMID- 1384627
TI  - The effect of different iron compounds on transferrin receptor expression in term
      human cytotrophoblast cells.
AB  - During pregnancy, the mother is faced with an increased food demand. A good
      example of this increased demand is iron (Fe). Fe is needed in all growing cells.
      During pregnancy, the Fe transport to the fetus increases enormously. This amount
      can easily induce an Fe deficiency in the mother. Fe supplementation is very
      important for her, but not for the Fe status of the fetus, which is protected
      against Fe toxicity as well as deficiency. The placenta seems to be autonomous in
      Fe uptake. Likely there is a regulation mechanism. The human placenta is
      hemomonochorial. The cell layer of the fetus in contact with the maternal blood
      is formed by syncytiotrophoblasts. Fe is transported to the placenta by
      transferrin. Transferrin binds to a transferrin receptor on the trophoblast
      membrane and is internalized via an endocytic pathway. During this cycle, Fe is
      released from transferrin and the transferrin-transferrin receptor complex is
      recycled to the membrane. Isolated trophoblast cells from term placentas form a
      syncytium in vitro, and transferrin receptors are expressed. Expression depends
      on the number of cells in culture, culture time, the amount of Fe available, and
      the Fe compound. By regulation of the number of transferrin receptors,
      trophoblasts are able to control their Fe uptake.

PMID- 1384628
TI  - The role of iron in experimental porphyria and porphyria cutanea tarda.
AB  - Porphyria cutanea tarda (PCT) and experimental porphyria are characterized by a
      decreased activity of the enzyme uroporphyrinogen decarboxylase, and accumulation
      of uroporphyrins and heptacarboxylporphyrins in the liver. Iron (Fe) plays an
      important role in PCT and experimental porphyria. Biochemically and electron
      microscopically, we examined the relationship between Fe and porphyrins in liver
      tissue of C57BL/10 mice made porphyric by administration of iron dextran as
      Imferon (IMF), and in liver biopsies of patients with symptomatic PCT.
      Accumulation of uroporphyrins and heptacarboxylporphyrins, and an increased
      amount of Fe were observed in livers of mice treated with IMF and in liver
      biopsies of patients with PCT. In mice treated with IMF, the activity of
      uroporphyrinogen decarboxylase was decreased. Both in livers of mice treated with
      IMF and in livers of patients with PCT, needle-like structures, representing
      uroporphyrin crystals, were observed by electron microscopy. Uroporphyrin
      crystals and Fe (as ferritin) were observed in the same hepatocyte. Moreover,
      there was a striking morphological correlation between uroporphyrin crystals and
      ferritin-Fe, suggesting a role for (ferritin-)Fe in the pathogenesis of
      porphyria.

PMID- 1384629
TI  - Dietary iron loading does not influence biliary iron excretion in rats.
AB  - The effect of dietary iron loading on biliary iron excretion was investigated
      with male Wistar rats aged 6 wk. The rats were fed purified diets with either 174
      or 1740 mg FeSO4. 7H2O/kg diet and demineralized water for 6 wk. Blood
      haemoglobin, hematocrit, and iron concentrations in kidney and heart were not
      affected and iron concentrations in liver, spleen, and tibia were significantly
      raised after feeding the high-iron diet. The high-iron diet did not raise biliary
      iron excretion, suggesting that biliary iron excretion does not play an important
      role in regulating iron metabolism in rat after dietary iron loading.

PMID- 1384630
TI  - Impaired iron status in rats as induced by copper deficiency.
AB  - The hypothesis was tested that marginal copper deficiency affects iron status.
      Copper restriction (1 vs 5 mg Cu/kg diet) significantly lowered iron
      concentrations and transferrin saturation in plasma and reduced blood hemoglobin,
      hematocrit, and iron concentrations in tibia and femur, but raised iron
      concentrations in liver. Marginal copper deficiency did not affect feed intake
      and bodyweight gain.

PMID- 1384631
TI  - Iron status in rats fed a purified diet without vitamin A.
AB  - The effect of vitamin A deficiency on iron status was investigated in rats. After
      28 d of feeding either low or high vitamin A diets (0 vs 4000 IU of vitamin A per
      kg feed), the final body weight was slightly but significantly lowered by the low
      vitamin A diet. Plasma retinol concentrations were decreased in rats fed diets
      low in vitamin A. Marginal vitamin A deficiency produced slightly, but
      significantly lower blood hemoglobin concentrations; it did not clearly affect
      hematocrit. The concentration of iron in liver was significantly higher when
      diets low in vitamin A were fed while significantly lower levels were observed in
      femur.

PMID- 1384632
TI  - High intakes of tin lower iron status in rats.
AB  - The effects of relatively low (1, 10, and 50 mg/kg) and high (100 and 200 mg/kg)
      dietary concentrations of tin (added as stannous chloride) on iron status of rats
      were determined. After feeding the diets for 28 d, feed intake and body weights
      were not significantly affected. Iron concentrations in plasma, spleen, and tibia
      as well as percentage transferrin saturation were decreased in rats fed the diets
      supplemented with 100 or 200 mg tin/kg. In rats fed the diet containing 200 mg
      tin/kg, group mean hemoglobin, hematocrit, and red blood cell count were slightly
      lowered but total iron binding capacity was not affected. Iron status was not
      influenced by dietary tin concentrations lower than 100 mg/kg. If these results
      can be extrapolated to humans, then it may be concluded that tin concentrations
      in the human diet, which range from 2 to 76 mg/kg dry diet, do not influence iron
      status in humans.

PMID- 1384633
TI  - Dietary fructose vs glucose does not influence iron status in rats.
AB  - The effect of dietary fructose vs glucose on iron status was studied in rats.
      Female rats were fed for 4 wk diets containing either fructose or glucose (709.4
      g monosaccharide/kg). Fructose vs glucose lowered iron concentrations in liver,
      kidney, and heart, but did not alter absolute iron contents.

PMID- 1384634
TI  - Effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on
      cytotoxicity of PSK-induced peritoneal polymorphonuclear leukocytes (PMNs).
AB  - We investigated whether recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) enhanced the cytotoxicity of PSK-induced polymorphonuclear leukocytes
      (PMNs) in the peritoneal cavity. Male C3H/He mice, 8- to 10-week-old, received
      single subcutaneous (s.c.) or intraperitoneal (i.p.) injection of 2.5
      micrograms/animal of rhG-CSF at different time points before or after an i.p.
      administration of PSK. In other experiments, mice were s.c. or i.p. treated with
      the same dosage of rhG-CSF every day for 7 or 14 consecutive days and i.p.
      injected with 2.5 mg/animal of PSK on the last day. Peritoneal PMNs were
      harvested 6 hrs after the administration of PSK and purified to more than 95% by
      Ficoll-Paque for in vitro cytotoxic assay. In vitro cytotoxic assays with 51Cr
      labeled MM46 mammary carcinoma cells were added with 5-20 micrograms/ml of
      Nocardia rubra cell wall skeleton (N-CWS) at the beginning of the assay to
      augment the cytotoxic activity of PMNs. In vitro addition of rhG-CSF to the assay
      did not enhance the cytotoxicity of PSK-induced PMNs. However, the cytotoxicity
      was significantly increased when rhG-CSF was s.c. administered 12 hrs before a
      PSK injection or 2 or 5 hrs after that. On the other hand, the cytotoxicity was
      rather weak when mice s.c. or i.p. received consecutive injections of rhG-CSF.
      This cytotoxicity may be mediated by H2O2, since H2O2 production of PMNs during
      the cytotoxic assay appears to correlate with the levels of cytotoxicity under
      suppressed H2O2 generation by catalase or enhanced generation by rhG-CSF. These
      results suggest that rhG-CSF augments the cytotoxicity of PSK-induced PMNs when
      administered in vivo timely.

PMID- 1384635
TI  - Overexpression of pp60c-src is associated with altered regulation of adenylyl
      cyclase.
AB  - The ability of activators of the beta-adrenergic receptor to elevate
      intracellular cAMP levels in murine fibroblasts is enhanced upon overexpression
      of avian c-src [Bushman et al. (1990) Proc. natn. Acad. Sci. U.S.A. 87, 7462
      7466]. To investigate the molecular basis for this effect, we prepared
      particulate fractions from control and pp60c-src overexpressing C3H10T1/2
      fibroblasts and assessed the relative abilities of several activators of the beta
      adrenergic receptor-Gs-adenylyl cyclase (AC) signal transduction pathway to
      stimulate the enzymatic response. Two- to three-fold increases in both the
      sensitivity and maximum responsiveness of AC to the beta-adrenergic agonist
      isoproterenol were consistently observed in fractions prepared from the c-src
      overexpressing cells. Interestingly, the AC response to two agents believed to
      act directly at the level of the G protein were either enhanced (NaF) or
      unaffected (GTP gamma S) by c-src overexpression. Finally, overexpression of c
      src was associated with a reduced ability of both Mn2+ and forskolin to activate
      AC directly. These results suggest that overexpression of wild type c-src may
      affect two distinct steps in the regulation of AC exerting a positive effect at
      the level of Gs activation and a negative effect on AC itself. As no differences
      in the relative number or affinity of beta-adrenergic receptors, or in the level
      of AC, Gs alpha or G beta, were detected between control cells and those
      overexpressing c-src, we propose that pp60c-src overexpression results in a
      modification of one or more components in this signal transduction pathway.

PMID- 1384636
TI  - T-cell and B-cell function in lupus.
AB  - B-cell hyperactivity is characteristic of lupus and appears to be, in many
      instances, T-cell driven. Recent work continues to examine the paradox of T-cell
      activation in vivo and depressed T-cell function in vitro. The role of intrinsic
      B-cell abnormalities, particularly in CD5+ B cells, is an area of active
      investigation.

PMID- 1384637
TI  - [Incidental carcinoma of the prostate].

PMID- 1384638
TI  - Aprotinin: its role in modifying perioperative blood loss.

PMID- 1384639
TI  - Morphoregulatory activities of E-cadherin and beta-1 integrins in colorectal
      tumour cells.
AB  - The cadherin family of adhesion molecules are prime mediators of cell-cell
      interactions while the integrins predominantly mediate cell-matrix and to a
      lesser extent cell-cell binding specificity. We have recently shown that a human
      colon carcinoma cell line (SW1222) organizes into glandular structures, with well
      defined polarity when cultured in three-dimensional type I collagen gel. The
      current study indicates that SW1222 cells display high levels of E-cadherin (E
      cd, epithelial cadherin) by western blotting and immunohistochemical staining. A
      monoclonal antibody (HECD-1) specific for human E-cd blocks cell-cell adhesion
      (100%) and inhibits (up to 75%) the glandular differentiation of SW1222 cells
      growing in collagen gel. Furthermore the anti-beta 1 integrin monoclonal antibody
      (mAb13) inhibits the glandular differentiation of SW1222 cells (61%) and their
      cellular binding to type I collagen (60%). However, no significant inhibition of
      cell-cell adhesion was demonstrated using mAb13 nor the anti-carcinoembryonic
      antigen monoclonal antibody (PR3B10). These results are consistent with E-cd
      being a cell-cell adhesion molecule expressed by SW1222 cells. These data
      indicate that E-cd and beta 1 integrins mediate cell-cell and cell-collagen
      interactions required for the induction and maintenance of the glandular
      differentiation of colorectal tumour cells. Thus the down-regulation or loss of E
      cd and beta 1 integrins seen in poorly differentiated colorectal tumours may
      represent one of the abnormalities underlying their progression towards an
      undifferentiated phenotype in vivo.

PMID- 1384640
TI  - High prevalence of Clostridium difficile diarrhoea during intensive chemotherapy
      for disseminated germ cell cancer.
AB  - A prospective, consecutive study of the aetiology of treatment-associated
      diarrhoea was conducted in 25 patients with disseminated germ cell cancer treated
      with intensive chemotherapy. Clostridium difficile was isolated in 45% of the
      diarrhoea episodes, which makes this species the most important bacterial
      pathogen in the development of clinically significant diarrhoea in this group of
      immunocompromised patients.

PMID- 1384641
TI  - Decay-accelerating factor (DAF, CD55) in normal colorectal mucosa, adenomas and
      carcinomas.
AB  - Decay-accelerating-factor (DAF, CD55), a phosphatidyl-inositol anchored
      glycoprotein, is a member of the cell membrane bound complement regulatory
      proteins that inhibit autologous complement cascade activation. DAF was found
      expressed on cells that are in close contact with serum complement proteins, but
      also on cells outside the vascular space and on tumour cells. Using CD55(BRIC110)
      and CD55(143-30) we show here that DAF(CD55) is only sporadically expressed on
      the luminal surface of normal colonic epithelium. However, 5/20 adenomas
      expressed DAF(CD55) on the cell surface of all tumour cells, 5/20 adenomas were
      completely negative, 10/20 adenomas expressed DAF(CD55) in various amounts.
      DAF(CD55) was expressed in various intensities on almost all tumour cells of the
      colon carcinoma cell line HT29. In 5/88 colorectal carcinomas DAF(CD55) was
      localised on the apical cell surface of all tumour cells, 31/88 were completely
      negative, 52/88 expressed DAF(CD55) in parts of their neoplastic populations.
      There was no correlation between the tumour grading, staging and location and the
      mode of DAF(CD55) expression, but DAF(CD55) was found more often in mucinous
      carcinomas (P = 0.007). Although the mode of DAF(CD55) expression is not
      correlated with tumour prognostic parameters, the upregulation of DAF(CD55) in a
      subset of adenomas and carcinomas needs further investigation concerning
      protection of tumour cells against complement cytotoxicity.

PMID- 1384642
TI  - Effects of tumour cells on angiogenesis and vasoconstrictor responses in sponge
      implants in mice.
AB  - The effects of tumour cells (Colon 26) on the development and response of new
      blood vessels to different vasoconstrictors (platelet activating factor; PAF,
      endothelin-1, angiotensin II, adrenalin and 5-hydroxytryptamine) have been
      investigated. Sponge implants in mice were used to host tumour cells while
      washout of 133Xe was employed to assess local blood flow in the implanted
      sponges. By 14 days after implantation the response of vessels in tumour-bearing
      implants to the various vasoconstrictors generally was decreased compared to that
      obtained in control sponge implants or adjacent normal skin. Thus at this time
      point the t1/2 for 133Xe washout from control sponges treated with adrenalin (0.5
      micrograms) was 30 +/- 4 min whereas in tumour-bearing sponges it was 5 +/- 1
      min. This decreased sensitivity in tumour vessels was probably not due to a
      complete lack of contractile elements since actin was demonstrated by
      immunohistochemistry around blood vessels in both types of implant. The results
      of the present study have shown that the pharmacological responses of blood
      vessels in a growing tumour, Colon 26, differed from the responses of vessels of
      a similar age in non-neoplastic tissue. These results appear to suggest that the
      different angiogenic stimuli released from tumour tissue may markedly influence
      pharmacological reactivity of newly formed blood vessels.

PMID- 1384643
TI  - Recombinant interferon alpha-2b in patients with metastatic apudomas: effect on
      tumours and tumour markers.
AB  - Malignant carcinoid tumours, islet cell tumours and medullary carcinomas of the
      thyroid are tumours with similar clinical features. In patients with unresectable
      or metastatic tumours leukocyte interferon (IFN) and recombinant human (rh) IFN
      have demonstrated efficacy. Twenty-four evaluable patients with progressive
      tumours were treated with 2.5 megaunits rh IFN alpha-2b, administered once daily
      subcutaneously, for a median duration of 7 months (range 0.5-37+). Two carcinoid
      patients demonstrated a response in tumour size, 80% showed stable disease (SD).
      Sixty percent of the carcinoid patients with elevated urinary 5
      hydroxyindoleacetic (5-HIAA) levels reached a biochemical partial response of the
      urinary 5-HIAA levels (median duration 13.5 months). In the patients with an
      islet cell or medullary tumour and an elevated tumour marker, the marker did not
      further increase. Of the 12 carcinoid patients evaluable for a symptomatic
      response, ten (83%) experienced a relieve of symptoms. IFN alpha-2b dose
      reduction or discontinuation due to toxicity was necessary in three and ten
      patients, respectively. No neutralising IFN alpha-2b antibodies developed despite
      prolonged treatment. In conclusion, IFN alpha-2b had a beneficial effect in
      patients with progressive tumours, while long-term IFN alpha-2b treatment did not
      augment neutralising antibodies. In view of the IFN alpha-2b-related toxicity,
      administration of IFN alpha-2b on alternating days may be preferable.

PMID- 1384645
TI  - Increased expression of tenascin in the dermis in scleroderma.
AB  - The expression of tenascin, a recently discovered extracellular matrix protein,
      was studied by immunohistochemical techniques in scleroderma skin and compared
      with its distribution in normal skin. In progressive systemic sclerosis, a marked
      increase in tenascin content was observed in the superficial reticular dermis. In
      localized scleroderma, the deposition of tenascin was increased both in the
      superficial and deep dermis of involved skin, whereas in clinically uninvolved
      skin the distribution of tenascin was the same as in normal control skin, i.e.
      the papillary dermis and peri-appendiceal zone. The distribution of tenascin did
      not strictly parallel that of fibronectin. These findings and the current
      knowledge of tenascin biology suggest that the overproduction of tenascin in
      scleroderma dermis could be secondary to stimulation of fibroblasts by immune
      cell-derived cytokines, or could be due to abnormal fibroblasts, or a
      subpopulation of fibroblasts, producing high levels of this extracellular matrix
      protein.

PMID- 1384644
TI  - Prior chemotherapy does not prevent effective mobilisation by G-CSF of peripheral
      blood progenitor cells.
AB  - In this study we demonstrate that the hemopoietic growth factor, G-CSF
      successfully mobilised progenitor cell populations into the peripheral blood in a
      population of patients despite intensive pretreatment with chemotherapy.
      Administration of G-CSF increased the numbers of peripheral blood progenitor
      cells (PBPC) by a median of 76-fold above basal levels. Maximal levels of PBPC
      were observed on days 5 and 6 after G-CSF treatment. In two patients a second
      cycle of G-CSF mobilised PBPC to levels comparable with those seen after the
      first cycle of G-CSF treatment. An earlier hemopoietic cell population (pre
      CFC's) was also mobilised with levels increased up to 50-fold above basal levels.
      Using a standard mononuclear cell leukapheresis technique the PBPC were collected
      extremely efficiently (essentially 100%) and could be further successfully
      enriched by separation using a Ficoll gradient. For patients who underwent the
      optimal collection protocol (i.e. leukapheresis on days 5, 6 and 7) a total of 32
      +/- 6 x 10(4) GM-CFC kg-1 were collected. The ability to mobilise PBPC using G
      CSF alone and to successfully and efficiently harvest these cells has important
      implications for the future of transplantation and high dose chemotherapy
      procedures.

PMID- 1384646
TI  - Similarity between mycobacterial and human epidermal antigens.
AB  - Eight out of 17 mouse anti-Mycobacterium leprae monoclonal antibodies (MAb) were
      previously observed to react with human nerve and skin antigenic determinants in
      cryostat sections, using an indirect immunoperoxidase technique. These
      observations suggested that antigenic mimicry may be involved in the development
      of the clinical manifestations of leprosy. In the present study we have extended
      our earlier findings by investigating sera from leprosy patients and MAb using
      Western blot technique. It was observed that 30 sera and their corresponding
      F(ab')2 fragments from isolated IgG fractions of both tuberculoid and lepromatous
      patients reacted with 40-50 epidermal proteins of molecular weights (MW) ranging
      from 10 to 130 kDa. Sera from 14 controls, however, showed similar reactivity
      patterns. Absorption of nine patient and control sera with M. tuberculosis, M.
      marinum and M. kansasii resulted in the removal of several components of
      different MW in nine, four and three cases, respectively. No consistent
      differences between sera from leprosy patients and controls were observed. Four
      out of eight MAb against M. leprae which reacted with determinants in human
      epidermis and/or dermis in skin cryostat sections reacted with epidermal proteins
      of MW higher than 39 kDa in Western blot. Four MAb which showed reactivity in
      cryostat sections did not react in Western blot. Another four MAb did react with
      human epidermal proteins in Western blot but did not react in cryostat sections,
      indicating that the MAb were reacting with different epitopes in the two systems.
      Five MAb did not react with human epidermal proteins either in cryostat sections
      or in Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384647
TI  - Human serum stimulates the production of G-CSF, IL-1, IL-6 and IL-8 by human
      peripheral blood leucocytes.
AB  - Human serum induces human peripheral blood leucocytes (PBL) to release an
      activity stimulating neutrophil colony formation (G-CSA) from human bone marrow
      cells. By titrating individual growth factors and using specific neutralizing
      antibodies we showed that: human serum contains very low levels of G-CSF which
      are by themselves insufficient to stimulate myeloid colony formation in primary
      human bone marrow cultures and cannot account for the serum releaser activity;
      that although no detectable levels of IL-1, IL-2, IL-3, IL-4, IL-6 or IL-8 are
      found in the serum, anti IL-1 antibodies partially block the release of G-CSA
      when added early during PBL incubation; that PBL incubated in the absence of
      serum for 2 d produce small amounts of IL-1, IL-6, IL-8 and G-CSF and this is
      increased 6-16 fold in the presence of human serum; and that the neutrophil
      colony-stimulating activity released by PBL incubated with human serum is G-CSF.

PMID- 1384648
TI  - Antigenic analysis of human haemopoietic progenitor cells expressing the growth
      factor receptor c-kit.
AB  - The cell surface molecule encoded by the protooncogene c-kit has recently been
      identified as the receptor for a growth factor variously termed stem cell factor
      (SCF), mast cell growth factor or steel factor. Using the c-kit antibody 17F11 we
      analysed, in triple staining experiments, the surface molecule profile and
      scatter characteristics of c-kit+CD34+ human haemopoietic progenitor cells. In 10
      normal bone marrow samples we found 19-51% of CD34+ bone marrow progenitor cells
      to coexpress c-kit. These c-kit+CD34+ bone marrow cells turned out to represent a
      phenotypically heterogeneous population. A considerable proportion coexpressed
      CD33 (52 +/- 23%), and/or CD71 (62 +/- 26) antigens, marker molecules previously
      shown to be expressed by committed in vitro colony forming cells but not by their
      precursors. In line with a relatively differentiated phenotype c-kit+CD34+ cells
      also gave rise to on average higher forward and right-angle light scattering
      signals. The proportions of CD38 and/or HLA-D expressing cells were similar in
      the c-kit+ and in the c-kit- subsets of CD34+ progenitor cells. Coexpression of
      CD19 was found to be less frequent in the c-kit+ (4 +/- 5%) as compared to the c
      kit- (17 +/- 14%) fraction of CD34+ cells. CD7+ CD34+ bone marrow cells were
      hardly detectable and their numbers too low to allow further subdivision in c
      kit+ and c-kit- subsets.

PMID- 1384649
TI  - Levels of complement regulatory proteins, CD35 (CR1), CD46 (MCP) and CD55 (DAF)
      in human haematological malignancies.
AB  - Levels of the membrane complement regulatory proteins, C3b/C4b receptor (CR1,
      CD35), membrane cofactor protein (MCP, CD46), and decay-accelerating factor (DAF,
      CD55), expressed on cells from patients with haematological malignancies and
      normal subjects were assessed by flowcytometry using the respective monoclonal
      antibodies (mAbs). All myeloid and most lymphoid leukaemia samples tested were
      CR1-negative: two of the 42 leukaemia samples expressed minute amounts of CR1.
      Lack of CR1 in leukaemia cells was confirmed with two mAbs raised against CR1,
      31R, and 243R, which recognized different epitopes and induced different degrees
      of CR1-mediated fluorescent shift on flow-cytometry in granulocytes and
      erythrocytes. MCP was increased in most chronic myelogenous leukaemia (CML) and
      chronic lymphocytic leukaemia (CLL), and was also increased in majority of acute
      nonlymphocytic leukaemia (ANLL), acute lymphocytic leukaemia (ALL) and non
      Hodgkin's lymphoma (NHL). Levels of DAF were also high in CML and CLL, and were
      variable in other types of leukaemia: some were DAF-negative while others
      expressed extremely high levels of DAF. In CML patients, the high level of MCP
      and the lack of CR1 were normalized after medical treatment. These results are in
      agreement with the data obtained with human leukaemia cell lines, and support the
      hypothesis that CR1 is essentially a differentiated cell antigen and that a high
      level of MCP reflects some malignant transformation or an immature stage in blood
      cells.

PMID- 1384650
TI  - Haemoglobin F levels in sudden infant deaths.
AB  - Fetal haemoglobin levels have been measured prospectively in 135 autopsy cases of
      sudden, unexpected infant deaths (31 pre-term, 104 full term) using standard
      laboratory methods. These results have been compared with Hb F values from a
      normal control group of 570 living infants (145 pre-term, 425 full-term) with a
      post-conceptional age < 90 weeks. The gestational age was established for all
      live controls and sudden infant deaths. The results show that full-term (> 38
      weeks gestational age) sudden infant death victims as a group have significantly
      elevated Hb F levels (chi 2 = 25.20, P < 0.001) when compared to the gestational
      age matched control group. Pre-term (< 38 weeks gestational age) SIDs show no
      significant differences from the pre-term control group (chi 2 = 1.20, n.s.) The
      division of the controls into pre- and full-term groups demonstrates major
      differences between the post-natal Hb F fall in pre- and full-term infants. Use
      of post-conceptional age as a growth marker does not produce comparability with
      full-term infants. Extensive controls were carried out to confirm the reliability
      of post-mortem Hb F assays, and comparability with in vivo estimation. No
      significant or systematic differences between pre- and post-mortem samples were
      identified, nor were any significant differences found on post-mortem storage up
      to 72 h.

PMID- 1384651
TI  - Prognostic irrelevance of CD34 in acute myeloid leukaemia.

PMID- 1384652
TI  - Are beta 1 integrins involved in Xenopus gastrulation?
AB  - The molecular basis of vertebrate gastrulation is poorly understood. Work on
      urodele amphibians has implicated beta 1-containing integrins, but the limited
      information available for Xenopus indicates otherwise: peptides containing the
      RGD sequence do not inhibit gastrulation and induction of cell spreading in
      presumptive ectodermal cells by activin is not accompanied by an increase in
      synthesis of integrin beta 1. Here we report that beta 1-containing integrins
      are, nevertheless, the principal fibronectin receptors in the Xenopus gastrula,
      although their cell surface levels are low. Antibodies recognizing the external
      domain of the molecule can, unlike peptides containing the RGD site, block
      gastrulation when introduced into the blastocoel. These results allow us to
      propose a model to explain the role of integrin beta 1 in Xenopus gastrulation.

PMID- 1384653
TI  - pp60c-src in human melanocytes and melanoma cells exhibits elevated specific
      activity and reduced tyrosine 530 phosphorylation compared to human fibroblast
      pp60c-src.
AB  - Elevated levels of pp60c-src tyrosine kinase activity have been implicated in
      both tumorigenesis and cell differentiation. We have found a 2- to 4-fold
      elevation in pp60c-src specific activity in certain human melanoma cell lines
      compared to human foreskin fibroblasts. This activation of pp60c-src did not
      appear to be related to melanoma tumor progression, because when normal human
      epidermal melanocytes were examined, it was found that they contained pp60c-src
      having a 7-fold elevation in specific activity compared to pp60c-src from human
      fibroblasts. It was determined that pp60c-src from melanocytes was not the
      neuronal form, pp60c-src+. Melanocyte pp60c-src exhibited a reduced level of
      phosphorylation on its carboxyl-terminal regulatory site, tyrosine 530, which
      might be responsible for its elevated specific activity. These results suggest
      that, in melanocytes, regulation of tyrosine 530 phosphorylation
      dephosphorylation favors activation of pp60c-src. This activation may be involved
      in the growth, differentiation, or function of human melanocytes.

PMID- 1384654
TI  - Localization of the viral and cellular Src kinases to perinuclear vesicles in
      fibroblasts.
AB  - Previous studies have shown that the viral oncogene product, v-Src, is localized
      to a perinuclear structure. Here, we demonstrate by immunofluorescence analysis
      that the perinuclear structure corresponds to a local concentration of vesicles.
      Overexpressed normal cellular Src, c-Src, and a temperature-sensitive mutant of v
      Src also are associated with these perinuclear vesicles. This perinuclear
      localization is observed in a variety of cell types using several different
      antibodies to Src, and it is independent of the fixation method. Immunoelectron
      ultracryomicroscopic analysis of rat fibroblast cells transformed by v-Src
      demonstrates an association of this protein with the limiting membranes of
      vesicles concentrated in the perinuclear region. These vesicles appear at the
      electron microscopic level to be multivesicular bodies on the basis of their size
      (0.3-1.0 microns in diameter), large electron-transparent lumens, and electron
      dense vesicular inclusions. Morphometric analysis indicates that approximately
      20% of the total cell v-Src protein is associated with these structures. This
      subpopulation of v-Src may have been recovered from the plasma membrane via the
      endocytotic pathway in a manner analogous to endocytosis of the epidermal growth
      factor receptor. Localization of the Src tyrosine kinases to these perinuclear
      endocytotic vesicles may be necessary for oncogenic transformation by v-Src and
      for normal functions of c-Src.

PMID- 1384655
TI  - Down-regulation of cytokeratin 14 mRNA in polyoma virus middle T-transformed rat
      liver epithelial cells.
AB  - We have recently shown that rat liver nonparenchymal epithelial cells, such as
      T51B cells, selectively express cytokeratin (CK) 14 as a partner of CK8 in their
      intermediate filaments, and we proposed CK14 as a unique cell lineage marker of
      the liver epithelial cell population (R. Blouin, M-J. Blouin, I. Royal, A.
      Grenier, A. Loranger, D. R. Roop, and N. Marceau, Differentiation, submitted for
      publication, 1992). In the present study, T51B-261A (spontaneously transformed)
      and T51B-261B (aflatoxin B1-treated) clones and clones derived from T51B cells
      transfected with SV40 large T (LT) and polyoma virus middle T (MT) were used to
      investigate CK gene expression in nontransformed and transformed liver epithelial
      cells. T51B-261A, T51B-261B, MT-T51B, and LT/MT-T51B clones all grew in calcium
      deficient medium and formed colonies in soft agar, whereas LT-T51B clones did not
      grow at all in either one of these assays. T51B-261A and T51B-261B clones formed
      small, slow growing tumors when injected into newborn syngenic rats, whereas the
      MT-T51B and LT/MT-T51B clones produced rapidly forming, large tumors. There was
      no effect of cell transformation on CK expression, except in the clones
      expressing MT, where the CK intermediate filaments were completely lost. Analyses
      of [35S]methionine incorporation into the Triton-resistant cytoskeleton and of
      total proteins confirmed that CKs were absent. In contrast, vimentin intermediate
      filaments remained unaffected in all of the clones.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1384656
TI  - Expression of the ETS2 and transferrin receptor genes in Philadelphia-positive
      chronic myeloid leukemia patients with a reciprocal t(3;21).
AB  - The translocation t(3;21)(q26;q22) is a rare recurring clonal abnormality, either
      preceding or associated with blast crisis in Philadelphia chromosome-positive
      chronic myeloid leukemia (CML) patients. We previously localized the chromosomal
      breakpoints at 3q26.2 and 21q22.2, using high resolution chromosomal analysis.
      Two genes of interest are localized near the breakpoints, the transferrin
      receptor gene and the ETS2 proto-oncogene. Their chromosomal localizations,
      determined by in situ hybridization on normal metaphase cells, were 3q29 and
      21q22.3, respectively. They underwent a reciprocal translocation in patients with
      t(3;21). Their structures were not altered by the translocation, and both were
      expressed to varying levels in t(3;21) patients. Southern blotting investigations
      showed that the structure of other single-copy genes, including FIM3, localized
      near the breakpoints, were not affected by the translocation. An analysis of ETS2
      expression performed on CML patients without t(3;21) showed the presence of the
      transcript in 100% of the blast crises, but only in 20% of the chronic-phase
      patients. Thus ETS2 expression may either be linked to or play a role in CML
      progression.

PMID- 1384657
TI  - Improved technique for short-term culture and cytogenetic analysis of human
      breast cancer.
AB  - Various growth media and procedures for tissue disaggregation and culturing were
      tested with regard to cell attachment, the type of cells to grow out, and the
      emergence of cytogenetically abnormal clones in cultures of 20 primary breast
      carcinomas. Clonal chromosome abnormalities were detected in 16 cases (80%). Our
      findings allow us to suggest a series of modifications of existing culturing and
      chromosome preparation techniques for breast cancer cytogenetic analysis. The
      improvements include: (1) combined mechanical and enzymatic disaggregation of the
      tumor samples, (2) initiation of short-term cultures in plastic flasks that have
      a Primaria-modified tissue culture surface or have been coated with Vitrogen 100,
      (3) use of serum-free growth medium, CDM-5, but with temporary (24 hours)
      enrichment with 20% FBS if rapid cell attachment is not achieved, (4) partial and
      sequential harvesting of the cultures, and (5) use of minimal volumes of
      hypotonic and fixative solutions during harvesting.

PMID- 1384658
TI  - Analysis of chromosome 12 aneuploidy in interphase cells from human male germ
      cell tumors by fluorescence in situ hybridization.
AB  - The i(12p) marker chromosome has been found to be a highly nonrandom chromosome
      abnormality associated with germ cell tumors (GCTs). We have previously shown
      that a chromosome 12 centromere specific alpha-satellite DNA probe detects the
      i(12p) by virtue of differences in the size of the signal originating from the
      i(12p) and normal chromosome 12 centromeres after fluorescence in situ
      hybridization (FISH) in metaphase and interphase cells of cultured GCT cell
      lines. We have now extended this analysis to 72 fresh GCT tumor biopsy specimens.
      Banded cytogenetic analysis was attempted on each of these tumors, 45 of which
      were found to be clonally abnormal. Data on i(12p) and chromosome 12 copy number
      obtained by FISH agreed well with those obtained by cytogenetic analysis. In
      addition, the FISH method made possible the detection and determination of i(12p)
      and the chromosome 12 copy number in cases in which conventional cytogenetic
      analysis was unsuccessful. We found the incidence of i(12p) in seminomas to be
      low (7%) compared to that in nonseminomas (75%) when tumor biopsy specimens were
      studied by FISH. Our results show that the FISH technique can be used reliably
      for detection of the diagnostically and prognostically useful i(12p) marker in
      GCT tumor biopsy specimens.

PMID- 1384659
TI  - Unicolor and bicolor in situ hybridization in the diagnosis of peripheral
      neuroepithelioma and related tumors.
AB  - The chromosome 22 breakpoint of the t(11;22) translocation of peripheral
      neuroepithelioma has been located, by fluorescence in situ hybridization, in the
      proximity of the interface between 22q12.1 and 22q12.2. Use of single cosmids or
      pools of cosmids of the flanking regions enables the monitoring of the
      translocation in interphase and in metaphase chromosomes. This method can now be
      routinely applied for the diagnosis of this translocation in mixed round cell
      tumors.

PMID- 1384660
TI  - Pleomorphic adenoma cells vary in their susceptibility to SV40 transformation
      depending on the initial karyotype.
AB  - Chromosomal aberrations involving 8q12 or 12q13-15 characterize two cytogenetic
      subgroups of salivary gland pleomorphic adenomas. As the tumors of the two groups
      differ in their clinical and histologic characteristics, we decided to determine
      their susceptibility to SV40 transformation. We transfected cell cultures from 13
      adenomas with aberrations involving 8q12 and from seven adenomas with involvement
      of 12q13-15 using an SV40 plasmid coding for the early region of the viral
      genome. Whereas all cultures with aberrations of 12q13-15 showed transformed
      foci, only 4 of the 13 cultures with 8q12 abnormalities showed foci of
      transformed cells. We also observed a much higher immortalization rate in the
      first group (3/7 vs. 1/13). All successfully transformed tumor cell cultures
      showed a relatively stable karyotype in the pre-crisis stage and a high mitotic
      index, were T-antigen positive, and had an extended life span in vitro.

PMID- 1384661
TI  - Fusion and amplification of two originally non-syntenic chromosomal regions in a
      mammary carcinoma cell line.
AB  - The FLG/FGFRI gene, encoding a receptor for members of the FGF family, is located
      at 8p11.2-p12. It is amplified, overexpressed, and not grossly rearranged in the
      MDA-MB-134 breast carcinoma cell line, whereas other genes from the
      pericentromeric 8p region are not amplified. The FGF4/HSTFI gene, located at
      11q13, is also amplified with a substantial portion of the 11q13 region, but is
      not overexpressed in MDA-MB-134 cells. In this cell line, amplified sequences
      constitute a large homogeneously staining region (HSR) which is part of a marker
      chromosome containing chromosome 8 and chromosome 11 sequences. Using probes for
      the FGF4/HSTFI and the FLG/FGFRI genes in fluorescence chromosomal in situ
      hybridization, we show that the HSR contains de novo fused and amplified 11q13
      and 8p11-p12 sequences associated in a complex structure containing approximately
      the same number of FGF4 and FGFRI genes. The significance of this genetic
      abnormality for MDA-MB-134 cells, and for breast carcinogenesis in general, is
      unknown, but may underlie a particular type of oncogene activation.

PMID- 1384662
TI  - Distinct breakpoints in band 11q23 of the t(4;11) and t(11;14) associated with
      leukocyte malignancy.
AB  - Several non-random translocation breakpoints associated with leukemia or lymphoma
      have been shown to occur in chromosome band 11q23 between the genes CD3G and
      PBGD, a distance of approximately 750 kb. A combination of yeast artificial
      chromosome (YAC) cloning, in situ hybridization, and pulsed field gel
      electrophoresis (PFGE) experiments has further refined the interval containing
      one of these breakpoints, t(4;11)(q21;q23), to within 200 kb of CD3G. We have
      extended the PFGE analysis to show that the t(4;11) breakpoint lies in a region
      of approximately 100 kb, situated 100 kb distal to CD3G. Furthermore, we show
      that a second 11q23 breakpoint, t(11;14)(q23;q32), which was also previously
      mapped between CD3G and PBGD, is distinct from that of the t(4;11) chromosome.
      The 11q23 sequences that are involved at the t(11;14) breakpoint are not present
      in a YAC containing the t(4;11) breakpoint. The t(11;14) breakpoint has been
      localized on the PFGE map of the CD3G-PBGD interval and is at least 110 kb distal
      to the t(4;11) breakpoint, thus demonstrating heterogeneity among 11q23
      breakpoints.

PMID- 1384663
TI  - Quantitative acute leukemia cytogenetics.
AB  - Using literature data on cytogenetic abnormalities in 3,612 cases of acute
      myeloid leukemia (AML) and 1,551-cases of acute lymphocytic leukemia (ALL), we
      have attempted to quantify the information value of finding the typical ALL- and
      AML-associated chromosome aberrations. Sensitivity, specificity, and predictive
      value of finding or not finding a given aberration were calculated for several
      diagnostic scenarios: for the differential diagnosis between ALL and AML when the
      patient is known to have acute leukemia, for the differential diagnosis among AML
      FAB subtypes in a patient with known AML, and for the differential diagnosis
      between ALL FAB subtypes in a patient with known ALL. The specificities were
      generally high, close to 1. The highest sensitivities in AML were found for +8,
      t(15;17)(q22;q11), t(8;21)(q22;q22), and -7 (all greater than 0.1), and in ALL
      for t(9;22)(q34;q11), t(4;11)(q21;q23), and +21 (again all greater than 0.1). In
      the AML subtypes, the highest sensitivities were 0.89 for t(15;17)(q22;q11) in
      M3, followed by 0.40 for t(8;21)(q22;q22) in M2, 0.30 for
      inv(16)(p13q22)/del(16)(q22)/t(16;16)(p13;q22) in M4, and 0.16 for
      t(9;11)(p21;q23) in M5. In the ALL subtypes, the highest sensitivities were 0.71
      and 0.11 for t(8;14)(q24;q32) and t(8;22)(q24;q11), respectively, in L3, 0.23 for
      t(9;22)(q34;q11) in L2, and 0.18 and 0.13 for +21 and t(4;11)(q21;q23),
      respectively, in L1. The highest (1.0) positive predictive values in the AML
      versus ALL comparison were found for t(1;3)(p36;q21), inv(3)(q21q26),
      t(6;9)(p23;q34), t(7;11)(p15;p15), t(8;16)(p11;p13), t(8;21)(q22;q22),
      t(15;17)(q22;q11), and, as sole anomalies, for +4, +9, and +11. In the reverse
      comparison, ALL versus AML, positive predictive values of 1.0 were found for
      t(1;14)(p32-34;q11), dup(I)(q12-21q31-32), t(2;8)(p12;q24), t(8;14)(q24;q32),
      t/dic(9;12)(p11-12;p11-13), t(10;14)(q24;q11), and t(11;14)(p13;q11). Among the
      AML subgroups, the highest predictive values were: 1.0 for M3 if t(15;17), 0.91
      for M2 if t(8;21), 0.86 for M4 if inv/del(16)/t(16;16), and 0.82 for M5 if
      t(9;11). Among the ALL subtypes, positive predictive values of greater than 0.8
      were reached only for the L3-associated aberrations t(2;8) (1.0), t(8;14) (0.95),
      t(8;22) (0.87), and dup(I) (0.80). The highest negative predictive values were in
      AML 0.98 that the disease is not M3 if t(15;17) is not found, and in ALL 0.96
      that the patient does not have L3 if a t(8;14) is not detected.

PMID- 1384664
TI  - Characterization of the submicroscopic deletion in the small-cell lung carcinoma
      (SCLC) cell line U2020.
AB  - The small-cell lung carcinoma cell line U2020 contains a submicroscopic,
      homozygous deletion that removes a chromosomal segment within 3p13-p14, including
      the locus D3S3. We have sublocalized 49 additional probes to the 3p13-p14.2
      region and have identified 7 new DNA markers that arise from within the U2020
      deletion. The estimated size of the deletion, based on marker density, is
      approximately 4-5 megabases (Mb). Including D3S3, 7 of the 8 markers have been
      linked by pulsed-field gel (PFG) electrophoresis over an area of approximately 2
      Mb. Including the one unlinked marker, PFG analysis accounts for about 3 Mb of
      the region. The U2020 deletion appears confined to the 3p13-p14.2 region and does
      not include the candidate tumor suppressor gene, protein-tyrosine phosphatase
      gamma (PTPG).

PMID- 1384665
TI  - Loss of heterozygosity for 10q loci in human gliomas.
AB  - Cytogenetic and RFLP studies have shown that chromosome 10 is frequently lost in
      tumor cells from glioblastomas, suggesting that a suppressor gene important in
      tumorigenesis is present on this chromosome. Forty-one tumors were examined for
      loss of heterozygosity at 23 loci on chromosome 10 to determine the smallest
      common deletion interval on this chromosome. Seven tumors did not lose
      heterozygosity for any of the markers. Twenty-three tumors lost an allele for all
      the informative loci. In 11 tumors heterozygosity was maintained at some loci and
      lost at other loci, indicating partial deletion of chromosome 10. The common
      region of deletion in these 11 tumors was located in 10q24-q26 between the
      markers pHUK-8 and pMCT122.2.

PMID- 1384666
TI  - Loss of the Y chromosome from normal and neoplastic bone marrows. United Kingdom
      Cancer Cytogenetics Group (UKCCG)
AB  - Loss of the Y chromosome is a feature of haematologically normal bone marrow in
      elderly males, but it is also found in haematological malignancy. We describe -Y
      as the sole karyotypic abnormality in 147 cases (66 from 802 unselected cases and
      a further 81 cases selected for -Y) with the following diagnoses: no
      haematological malignancy (N), myelodysplastic syndrome (MDS), acute myeloid
      leukaemia (AML), and myeloproliferative disorder (MPD). The frequency of -Y in
      the 802 unselected N, MDS, and AML cases was 7.7%, 10.7%, and 3.7%, respectively.
      It could not be evaluated in MPD because there were too few cases. In N and MDS
      cases the frequency increased in a similar fashion over the age of 60 years. The
      147 -Y cases showed a similar increase in distribution with advancing age in all
      four clinical categories. The degree of loss of Y (% -Y cells per patient)
      increased with age in N and MPD patients but not in those with MDS or AML. This
      study suggests that in elderly men -Y is not indicative of malignancy and should
      not be considered as a marker of the malignant clone.

PMID- 1384667
TI  - Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide
      repeat polymorphism.
AB  - Loss of heterozygosity at the TP53 locus occurs frequently in many types of
      cancer and requires polymorphic markers for detection. Several polymorphisms at
      the TP53 locus have been described previously, and polymerase chain reaction
      (PCR)-based assays have been developed to detect these polymorphisms. However,
      these polymorphisms have relatively low levels of heterozygosity and are often
      uninformative. We report here the detection of loss of heterozygosity at the TP53
      locus in various human cancers by using a highly informative dinucleotide repeat
      polymorphism.

PMID- 1384668
TI  - Deletions in the short arm of chromosome 8 are present in up to 90% of human
      colorectal cancer cell lines.
AB  - Cytogenetic analyses of human colon cancer cells have revealed non-random
      deletions in chromosome arm 8p, among other chromosomal changes. By using 8p
      specific DNA probes we could identify allelic loss in 87% of colon cancer cell
      lines. Corresponding analyses in direct preparations of colon tumor tissues
      revealed a minimal value of 40% of allelic loss but were obstructed in many
      instances by contaminating normal tissue. These findings add to the number of non
      random genetic alterations occurring during colon carcinogenesis.

PMID- 1384669
TI  - Is cancer cytogenetics reducible to the molecular genetics of cancer cells?
AB  - Whether cancer cytogenetics can be reduced to the molecular genetics of cancer
      cells is a question that must be addressed in three domains, focusing on its
      ontological, methodological, and epistemological dimensions. The possibility of
      ontological reduction hinges on whether chromosomes have other important
      constituents than molecules. Although this must obviously be answered in the
      negative, it should be emphasized that both cytogenetic and recombinant DNA
      investigations provide us with very selective pictures of genomic organization.
      This is of concern because the higher order packing of DNA and its joining with
      other molecules to form chromosomal structures give rise to emergent properties,
      functional features that become manifest only at higher levels of complexity and
      that may not be deducible from the base pair composition of the DNA. A position
      of extreme methodological reductionism would in our context be that the best
      research strategy is always to investigate the genetic changes of tumor cells at
      the highest possible resolution level, as alterations of genes and, ultimately,
      as changes in DNA primary structure. There are two fundamental differences
      between cytogenetic and molecular genetic techniques that make this stance
      untenable. First, whereas cytogenetic investigations are open-framed (all
      chromosome aberrations are revealed), molecular genetic analyses are highly
      specific (only those aberrations are revealed that one tests for). Second,
      whereas the molecular approach determines the genotypic constitution of an
      idealized, average tumor cell, cytogenetic analysis is of real, individual cells.
      These may not necessarily be representative of the main population of the tumor,
      but at least whatever karyotypic differences exist between them are detected.
      Heterogeneity and clonal evolution within the tumor can thereby be
      assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384670
TI  - Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior
      uveal melanoma.
AB  - We present ten cases of posterior uveal melanoma which were karyotyped after
      short-term culture. One tumour had a normal chromosome complement. The remaining
      nine tumours were cytogenetically abnormal, with chromosomes 3, 6, 8, 11, and 13
      most frequently involved. Abnormalities of chromosome 13 were seen in two cases,
      chromosome 11 in three cases, and chromosomes 3, 6, and 8 in five cases. Four
      tumours, all derived from the ciliary body, demonstrated monosomy 3 and i(8q),
      confirming the involvement of these aberrations with a subgroup of uveal
      melanomas arising from the ciliary body.

PMID- 1384671
TI  - Molecular characterization of chromosome 22 deletions in schwannomas.
AB  - Schwannomas are tumors of the cranial, spinal, and peripheral nerve sheaths that
      originate from Schwann cells. Acoustic neurinomas are the most frequent cranial
      schwannomas. They might develop sporadically or in the context of
      neurofibromatosis type 2 (NF2). Loss of part or all of chromosome 22 is
      frequently found in acoustic schwannomas, suggesting that the NF2 gene is a tumor
      suppressor gene involved in the genesis of these tumors. Only a few spinal
      schwannomas have been molecularly characterized so far, showing that chromosome
      22 loss might also occur in these tumors. Here we present the molecular analysis
      of chromosome 22 in 23 acoustic schwannomas and nine schwannomas of other
      locations (including other cranial nerves and spinal and peripheral nerves). Most
      of these tumors were from sporadic cases. Multiple schwannomas of various
      locations were analyzed in two patients with NF2. We found partial or complete
      monosomy for chromosome 22 in 22% of the acoustic schwannomas and 55% of the non
      acoustic schwannomas. The tumors with partial monosomy included four with
      terminal deletions and one with a deletion of the centromeric part of the long
      arm of chromosome 22. The region between the beta B2-1 crystallin locus (CRYB2A)
      and the myoglobin locus (MB) was commonly deleted in these tumors. Our studies
      suggest that a schwannoma-related tumor suppressor gene within this region, which
      might be the NF2 gene, is involved in the development of schwannomas of various
      locations in the nervous system. Our studies indicate that the second hit in the
      genesis of different schwannomas within one (predisposed) NF2 patient occurs
      independently and via different mechanisms.

PMID- 1384672
TI  - Cytogenetic studies on 19 papillary thyroid carcinomas.
AB  - Short-term cultures from 19 papillary thyroid adenocarcinomas revealed clonal
      numerical and/or structural chromosomal changes in 13 tumors, nonclonal
      abnormalities in one tumor, and only normal karyotypes in five tumors. Clonal
      abnormalities of chromosome 10 were present in three tumors, two of which had the
      translocation t(7;10)(q35;q21). Numerical abnormalities of chromosome 17 were
      detected in two tumors.

PMID- 1384673
TI  - Cytogenetic and molecular genetic characterization of papillary thyroid
      carcinomas.
AB  - A combined cytogenetic and molecular analysis was performed on 11 cases of
      papillary thyroid carcinoma. A simple karyotypic abnormality was detected in five
      tumors, whereas six had no apparent chromosome change. In four of five rearranged
      cases the presence of a specific chromosomal abnormality involving chromosome 10
      (cases 1 and 2) and chromosome 1 (cases 3 and 4) was associated with the
      rearrangement of two protooncogenes: RET and NTRKI (formerly trk), respectively,
      with different donor genes. Moreover, the chromosomal localization of the
      involved genes and the type of chromosomal change observed suggested that RET and
      NTRKI activation occurred by intrachromosomal rearrangements. The six cases with
      normal karyotype did not show RET or NTRKI activation. These findings suggest
      that a combined cytogenetic and molecular approach would be useful in
      understanding the pathogenesis of thyroid neoplasia.

PMID- 1384674
TI  - Preferential chromosome loss in human papilloma virus DNA-immortalized mammary
      epithelial cells.
AB  - Human papilloma virus (HPV) DNA-immortalized human mammary epithelial cells may
      provide a model system for studying the molecular basis of immortalization and
      its role in breast neoplasia. Cytogenetic analyses were performed on clones
      derived from HPV 16- and HPV 18-immortalized human mammary epithelial cells. The
      majority of the clones contained near-diploid karyotypes. The single most
      frequent whole-chromosome loss was that of chromosome 19. Regions that showed
      preference for deletion and/or translocation included 2pter, 11qter, and 15pter.
      Evidence of chromosome 19 loss was confirmed by polymerase chain reaction (PCR)
      generated, chromosome 19-specific, dinucleotide microsatellite repeat
      polymorphism analysis.

PMID- 1384675
TI  - Characterization of the translocation breakpoint sequences of two DEK-CAN fusion
      genes present in t(6;9) acute myeloid leukemia and a SET-CAN fusion gene found in
      a case of acute undifferentiated leukemia.
AB  - The t(6;9) associated with a subtype of acute myeloid leukemia (AML) was shown to
      generate a fusion between the 3' part of the CAN gene on chromosome 9 and the 5'
      part of the DEK gene on chromosome 6. The same part of the CAN gene appeared to
      be involved in a case of acute undifferentiated leukemia (AUL) as well, where it
      was fused to the SET gene. Genomic sequences around the translocation breakpoint
      were determined in two t(6;9) samples and in the case of the SET-CAN fusion.
      Although coexpression of myeloid markers and terminal deoxynucleotidyl
      transferase was shown to be one of the characteristics of t(6;9) AML, no addition
      of random nucleotides at the translocation breakpoint could be found. In
      addition, the breakpoint regions did not reveal heptamer-nonamer sequences,
      purine-pyrimidine tracts, a chi-octamer motif, or Alu repeats. The sequence in
      which the translocation breakpoints occurred was enriched in A/T. Notably, the
      specific introns in which clustering of breakpoints occurs in DEK and CAN both
      contain a LINE-I element. As LINE-I elements occur with a moderate frequency in
      the human genome, the presence of such an element in both breakpoint regions may
      be more than coincidental and may play a role in the translocation process.

PMID- 1384676
TI  - Whole-arm t(1;16) and i(1q) as sole anomalies identify gain of 1q as a primary
      chromosomal abnormality in breast cancer.
AB  - Cytogenetic analysis of four ductal breast carcinomas revealed net gain of 1q in
      all tumors. In the first tumor, the only change was that one chromosome 16 was
      replaced by a derivative chromosome consisting of 16p and 1q. The same unbalanced
      whole-arm translocation was also found in the second tumor, as the only
      aberration in one of four abnormal clones. In the last two cases, which also were
      characterized by cytogenetically unrelated clones, an extra i(1q) was present in
      one clone in both tumors as the sole aberration. Our findings suggest that gain
      of 1q is a primary chromosomal abnormality in breast carcinomas, in the sense
      that it is an early event that precedes the acquisition of more complex changes.

PMID- 1384677
TI  - Recurrent abnormalities of chromosome bands 10q23-25 in non-Hodgkin's lymphoma.
AB  - Many nonrandom chromosome abnormalities have been associated with non-Hodgkin's
      lymphomas (NHL). Some of these are nonspecific changes seen in many different
      histologic subtypes. We describe a series of abnormalities of chromosome bands
      10q23-25 seen in 159 consecutive NHL patients with abnormal cytogenetic findings.
      The proportion of karyotypes with abnormalities of 10q varied from 3% among the
      immunoblastic lymphomas to 67% in the diffuse large cleaved cell lymphomas.
      Seventeen (10.7%) had abnormalities of 10q23-25. All but one of these were B-cell
      tumors. The abnormalities consisted of six deletions and 11 translocations.
      Sixteen of the 17 patients had the 10q abnormality when cells were first
      karyotyped. The remaining patient acquired the 10q abnormality in the third of a
      series of biopsies. In the follicular histologic subtypes [follicular small
      cleaved cell (FSC), follicular mixed small cleaved and large cell (FM), and
      follicular large cell noncleaved (FL-NC)], abnormalities of 10q were found in
      nine patients, all in association with abnormalities of 14q32. Seven of these
      were associated with the t(14;18)(q32;q21). Overall, 10q23-25 abnormalities were
      observed in 11.9% (8/67) of low-grade [small lymphocytic (SL), FSC, and FM]
      lymphoma cases. DNA was available from five patients with abnormalities of 10q
      and was probed for rearrangements with the HOXII (TCL3) oncogene probe. As
      expected, we did not find such rearrangements in these five patients with B-cell
      tumors. Abnormalities of 10q23-25 have been reported previously in NHL but not at
      this frequency.

PMID- 1384678
TI  - Molecular cloning and analysis of chromosome band 11q23 involved in leukaemia
      associated translocations.
AB  - Three overlapping yeast artificial chromosomes (YACs) spanning a 780 kb region of
      DNA around the CD3 locus on chromosome 11 have been isolated and characterised.
      The individual cloned regions have been mapped by in situ hybridisation to
      chromosome band 11q23, and a restriction enzyme map of this region has been
      constructed. The positions of these clones in relation to a series of leukaemia
      associated chromosomal translocations has also been determined. It was concluded
      that, although two clones lay entirely proximal to the breakpoints examined, the
      third clone (13HH4) encompassed the breakpoints for the translocations t(4;11),
      t(6;11), and t(9;11). The t(9;11) was observed in an acute myeloid leukaemia in a
      patient previously treated for an unrelated malignancy. It would thus appear that
      the breakpoints at chromosome band 11q23 occurring in therapy-related leukaemias
      are in the same region as those found in adult and childhood acute leukaemias and
      may result from a common underlying mechanism.

PMID- 1384679
TI  - Translocations involving 12p in acute myeloid leukemia: association with prior
      myelodysplasia and exposure to mutagenic agents. United Kingdom Cancer
      Cytogenetics Group (UKCCG).
AB  - Six cases of acute myeloid leukemia (AML) with translocations involving 12p are
      described. The patients were one child age 7 yrs and five adults with an age
      range of 20-66 yrs (median 46 yrs). In two patients AML followed treatment for
      acute lymphoblastic leukemia (ALL), in one case after 11 years disease-free
      survival. Of the remaining four patients, two had been occupationally exposed to
      possible mutagens and three had a previous myelodysplastic phase. Two patients
      achieved complete remission; survival for the six cases was between 1 and 24
      months (median 6.5 months). The breakpoints in 12p occurred in p11, p12, and p13,
      indicating that several sites are important in these rearrangements, and it is
      suggested that t(12;17)(p11;q11) is a new nonrandom abnormality in AML.

PMID- 1384680
TI  - Translocations involving 9p and/or 12p in acute lymphoblastic leukemia. United
      Kingdom Cancer Cytogenetics Group (UKCCG).
AB  - Fifteen cases of acute lymphoblastic leukemia (ALL) with translocations involving
      9p and/or 12p are described. Four children, three males and one female, age range
      1-8 yrs, had translocations involving 9p but not 12p. Of these, three had B
      lineage ALL and one had biphenotypic T-ALL/acute myeloid leukemia. Six patients,
      three males and three females, age range 1-49 yrs, had translocations involving
      12p but not 9p. Five had B-lineage ALL and one had T-ALL. One patient had
      dic(7;12)(p11;p11), confirming that this previously reported translocation is
      nonrandom in ALL. One patient had t(2;12)(q14;p13), and it is suggested that this
      may also be a new nonrandom abnormality. Five patients, four males and one
      female, age range 11-21 yrs, had common ALL and dic(9;12). The dic(9;12) appears
      to confer a better prognosis than do other translocations involving 9p or 12p.

PMID- 1384681
TI  - Clonal 6p21 rearrangement is restricted to the mesenchymal component of an
      endometrial polyp.
AB  - Previous cytogenetic analyses revealed t(6;20)(p21;q13) in two endometrial
      polyps. We karyotyped a large endometrial polyp in which 19 of 25 metaphase cells
      contained a t(1;6;4)(q21;p21;q13). Subsequent combined
      immunohistochemical/cytogenetic analysis showed all aberrant metaphase cells to
      be of mesenchymal derivation, whereas epithelial cells from the polyp were
      diploid. These studies indicate that rearrangement of chromosome band 6p21 is a
      characteristic cytogenetic aberration in the stromal component of endometrial
      polyps.

PMID- 1384682
TI  - The der(11) chromosome contains the critical breakpoint junction in the 4;11,
      9;11, and 11;19 translocations in acute leukemia.
AB  - Translocations involving 11q23 are recurring abnormalities in human acute
      leukemia cells of either lymphoid or myeloid lineage. Analysis of 13 variant
      translocations associated with four of these [t(4;11), t(6;11), t(9;11) and
      t(11;19)] reveals that the der(11) chromosome is conserved in all of them and
      therefore contains the critical genetic rearrangement. The MLL gene
      (myeloid/lymphoid leukemia) is involved in each of these translocations. It is
      transcribed from centromere to telomere. The present analysis indicates that the
      5' region of MLL on the der(11) is juxtaposed to the coding sequences of genes on
      each of the other translocation partners.

PMID- 1384683
TI  - Variant translocations in two Burkitt's lymphoma cell lines are located in the
      MLV14 locus.
AB  - The human MLV14 locus, located 20 kilobases 3' of MYC, is rearranged in two
      Burkitt's lymphoma cell lines with either a t(2;8)(p12;q24) or t(8;22)(q24;q11).
      Alterations of MLV14 may have prognostic significance in some types of B-cell
      malignancies.

PMID- 1384685
TI  - Expression of the CD2 molecule on human B lymphoid progenitors.
AB  - CD2 expression on human B lymphoid progenitor cells was examined. By
      immunofluorescence analysis, a small fraction of bone marrow B cells was found to
      express CD2 on their surface. CD2 expression was not demonstrated on peripheral B
      cells. Epstein-Barr virus-transformed B cell lines derived from fetal liver at 8
      weeks of gestation were analyzed to delineate the expression and function of CD2
      at the early stage of human B cell development. Characterization of surface and
      genomic phenotypes of cell lines revealed that the established cell lines
      represent at least three different phenotypic characteristics of early B lineage
      cell: B progenitor, pre B, or early B cell. None of the 18 cell lines and 13
      subclones with the phenotype of the early B lymphoid cells initially expressed
      CD2 antigen. However, CD2 expression was induced by the successive cultivation of
      some cloned B progenitor cell lines. In spite of the expression of CD2, these
      clones cell lines were unable to form rosettes with sheep red blood cells. By
      immunoprecipitation analysis, an identical 50 kDa protein was precipitated with
      anti-CD2 antibody from the lysates of the radioiodinated CD2+B progenitor cell
      line and peripheral blood T cells. Anti-CD2 antibody induced significant
      enhancement of proliferation of the CD2+B progenitor subline. These data indicate
      that human CD2 is expressed on a fraction of B lineage cells at a very early
      differentiation stage and may play a role in B lymphopoiesis.

PMID- 1384684
TI  - Head and neck squamous cell carcinoma cell lines.

PMID- 1384686
TI  - Peptide-conjugated hapten groups are the major antigenic determinants for
      trinitrophenyl-specific cytotoxic T cells.
AB  - Several trinitrophenyl (TNP)-specific mouse cytotoxic T cell (CTL) clones
      recognize TNP-conjugated peptides in association with class I MHC molecules
      ('hapten-peptide determinants'). However, cell modification with trinitrobenzene
      sulfonic acid (TNBS) also leads to the formation of TNP determinants covalently
      attached to MHC molecules ('altered self'). To determine the importance of
      'peptide' versus 'altered self' determinants, we used the mutant cell line RMA-S
      which expresses peptide-free ('empty') Kb and Db molecules at 26 degrees C.
      Additionally, we stabilized Kb molecules on RMA-S cells at 37 degrees C using the
      Kb binding heptapeptide N53-59 derived from the vesicular stomatitis virus
      nucleoprotein. Lacking lysine, this peptide remains unmodified by TNBS and,
      therefore, only allows the formation of 'altered self' TNP determinants on
      occupied Kb molecules. RMA-S targets, pretreated or untreated with N53-59, upon
      TNBS modification were only lysed poorly or not at all by four different TNP
      specific CTL. In contrast, all of these clones efficiently lysed TNBS-treated,
      unmutated RMA cells, and three of them strongly reacted with RMA or RMA-S cells
      in the presence of tryptic TNP-BSA peptides. Moreover, the clone unreactive for
      TNP-BSA peptides also recognized TNP self-peptides extracted from TNBS-treated
      syngeneic spleen cells. Taken together, these data clearly show that TNP residues
      linked to MHC via associated peptides but not by covalent bondage represent the
      dominant antigenic epitopes for class I MHC-restricted, hapten-specific T cells.

PMID- 1384687
TI  - Differential expression of three CD45 alternative structures on murine T cells:
      exon 6-dependent epitope as a marker for functional heterogeneity of CD4+ T
      cells.
AB  - We prepared a novel rat mAb specific for CD45 molecules bearing the epitope coded
      for by the alternative exon 6 of the murine CD45 gene (CD45RC). Together with
      available mAbs to alternative exon 4- and 5-dependent epitopes (CD45RA and CD45RB
      respectively), we found that the three alternative exons show differential
      expressions on murine lymphocytes. Flow cytometry analysis revealed that although
      B cells were homogeneously CD45RA+B+C+, the CD4+ T cells clearly included two
      populations, CD45RA-B+C- and CD45RA-B+C+. The CD8+ T cells were separated into
      CD45RA-B+C+ and CD45RA+B+C+ populations. Such features of epitope expression on
      the cell surface correlate well with message levels of corresponding alternative
      exons. In the CD4+ T cells, messages of alternative exons were associated with
      either one or two exon forms of the CD45 transcript. In CD8+ T cells, there were
      transcripts with one, two, or three alternative exons. When stimulated by an
      immobilized CD3 mAb, the CD45RC+CD4+ T cell subset preferentially secreted IL-2
      and CD45RC-CD4+ T cells produced IL-4. Upon stimulation with concanavalin A,
      CD45RC-CD4+ T cells converted to CD45RC+ cells, and the level of CD45RC
      expression on the CD45RC+CD4+ T cell subset was up-regulated. These changes were
      unidirectional and irreversible. Therefore, differential expression of CD45RC
      probably delineates the functional heterogeneity of murine CD4+ T cells that is
      associated with the stages of CD4+ T cell maturation or activation.

PMID- 1384688
TI  - Evidence against a pathogenetic role for endothelin in pre-eclampsia.
AB  - OBJECTIVE: To assess whether increased placental or systemic endothelin synthesis
      has a pathogenic role in pre-eclampsia (gestational proteinuric hypertension).
      DESIGN: Prospective observations study. SUBJECTS: 19 women with pre-eclampsia and
      10 healthy pregnant women were studies. All were in the last trimester. MAIN
      OUTCOME MEASURES: Preproendothelin-1 gene expression by Northern blot analysis
      and generation of endothelin-1 precursor, big-endothelin-1, and endothelin
      isoforms, namely endothelin-1, 2 and 3, were assessed by specific radio
      immunoassays, in placental tissue. Plasma endothelin-1 levels and urinary
      excretion of big-endothelin-1 and endothelin-1 were measured. RESULTS: Placental
      preproendothelin-1 gene expression and immunoreactive big-endothelin-1 and
      endothelin-1, 2 and 3, were comparable in placental tissue from pre-eclamptic and
      normal pregnant women. Plasma levels of endothelin-1 did not differ between pre
      eclamptic and normal pregnancies. In contrast, urinary excretion of endothelin-1,
      which is likely to reflect the renal synthesis of the peptide, was significantly
      decreased in pre-eclamptic, as compared with normal pregnant women. This was not
      due to a decreased renal generation of endothelin-1 precursor, since urinary
      excretion of big-endothelin-1 did not differ between pre-eclamptic and normal
      pregnancies. These data suggest an increased renal endothelin-1 breakdown in pre
      eclampsia. CONCLUSIONS: Endothelin is unlikely to play a role in the pathogenesis
      of pre-eclampsia. Instead, an increased renal breakdown may have a role in
      limiting the negative effects of other vasoactive factors on the renal
      circulation.

PMID- 1384689
TI  - [Study on the therapeutic effects of interferon and gamma-globulin in
      experimental Pneumocystis carinii pneumonia].
AB  - This study was performed to observe the therapeutic effects of interferon
      gamma(IFN-gamma) and gamma-globulin(gamma-globulin) in experimental Pneumocystis
      carinii pneumonia of immune suppressed mice. After 9 weeks, trimethoprim
      sulfamethoxazole(TMP-SMZ; 10-50 mg/mouse/day), mouse IFN-gamma(5 x 10(4)
      units/mouse/day) and mouse gamma-globulin(20 mg/mouse/day) were administered to
      the mice for 3 weeks by the experimental group. The therapeutic efficacy was
      evaluated by body weights, histopathologic and electron microscopic findings of
      the lungs, and number of P. carinii cysts by Gomori's methenamine silver stain.
      Body weights of the mice were significantly increased in the group of combination
      therapy of TMP-SMZ with IFN-gamma or gamma-globulin, and in the group of TMP-SMZ
      treatment (p < 0.05), however, little effect was found in the group of gamma
      globulin alone. Histopathologic findings of P. carinii pneumonia were much
      improved in the group of combination therapy of TMP-SMZ with IFN-gamma. Treatment
      with either TMP-SMZ or IFN-gamma significantly reduced the number of cysts in the
      P. carinii pneumonia, but gamma-globulin alone was ineffective. In electron
      microscopic findings of P. carinii pneumonia, the number of trophozoites and
      cysts were reduced by treatment with either TMP-SMZ or IFN-gamma, and most of the
      cysts were empty or containing one or two intracystic bodies. The present results
      suggested, that combination therapy of TMP-SMZ with IFN-gamma had synergistic
      effects in treatment of P. carinii pneumonia in experimental mice.

PMID- 1384691
TI  - Idiopathic choriovitreal membrane--a case report.
AB  - A case of a macular idiopathic choriovitreal membrane is described which
      developed in a diabetic man. On initial examination the patient was found to have
      a pigment epithelial detachment with a choroidal neovascular membrane (CNVM) in
      the right eye. Two months after the first visit the CNVM was seen to have
      penetrated the retina and presented as a choriovitreal membrane. Panretinal
      photocoagulation was applied after which the choriovitreal membrane demonstrated
      fibrotic involution. This case is unusual in that the choriovitreal membrane
      developed in the absence of a choroidal or retinal pigment epithelial disease
      process that may be associated with a CNVM as well as in the absence of previous
      macular laser treatment.

PMID- 1384690
TI  - Bilateral congenital mydriasis.
AB  - A single case of bilateral congenital mydriasis is described. A review of the
      literature is presented and possible modes of inheritance are discussed.

PMID- 1384692
TI  - Embryonal form of extraskeletal myxoid chondrosarcoma with intermediate filament
      positive hyaline-like globules.
AB  - Reported is a case of an embryonal form of extraskeletal myxoid chondrosarcoma.
      The tumor cells contained PAS-positive, eccentrically located intracytoplasmatic,
      hyaline-like globules. These globules seemed to be a hallmark of this tumor, and
      they reacted strongly with cytokeratin and S-100 protein antibodies. The tumor
      was negative in reactions with desmin and GFAP antibody.

PMID- 1384693
TI  - S100 alpha, CAPL, and CACY: molecular cloning and expression analysis of three
      calcium-binding proteins from human heart.
AB  - Elevated levels of intracellular calcium are a major cause of myocardial
      dysfunction. To find possible mediators of the deregulated calcium we searched
      for EF-hand calcium-binding proteins of the S100 family. By PCR technology we
      identified three members of the S100 protein family (S100 alpha, CACY, and CAPL)
      in the human heart. We cloned the corresponding cDNAs and examined their
      expression levels in various human tissues by Northern blot analysis. All three
      proteins are expressed at high levels in the human heart. Whereas CACY and CAPL
      mRNAs are expressed ubiquitously, S100 alpha mRNA is restricted to heart,
      skeletal muscle, and brain. Interestingly, the expression pattern of S100 alpha,
      CACY, and CAPL in human tissues differs significantly from that in rodent
      tissues.

PMID- 1384694
TI  - RNA binding assays for Tat-derived peptides: implications for specificity.
AB  - RNA recognition by the HIV Tat protein is mediated in part by an arginine- and
      lysine-rich basic subdomain implicated as a signature element in proteins that
      bind RNA. Relative RNA binding affinities for a 14-residue peptide derived from
      Tat that spans the basic region are determined using a competition protocol.
      Binding specificity is compared with complexation by a 38-residue model for the
      RNA binding domain of Tat using the same approach. Binding strength for the
      minimal (14 residue) peptide is correlated with that for the longer peptide: both
      peptides recognize a short, bulged duplex. However, the shorter peptide
      dissociates more rapidly from the wild-type site and discriminates less well
      between nonspecific (double-stranded RNA) and specific sites. Relative
      dissociation constants for 38-residue peptide determined from direct partition
      and competition assays differ; the former assay consistently predicts stronger
      discrimination against RNAs with mutations in the stems flanking the bulge.
      Differences between the two assays are reconciled in terms of contributions from
      labile binding which is unstable to native gel electrophoresis. Kinetic stability
      may constitute a major specificity determinant for basic subdomain-mediated
      recognition of RNA.

PMID- 1384695
TI  - Circular dichroism studies suggest that TAR RNA changes conformation upon
      specific binding of arginine or guanidine.
AB  - Short basic peptides from the HIV Tat protein bind specifically to a bulge region
      in TAR RNA, with a single arginine residue providing the only sequence-specific
      contact. The free amino acid arginine also binds specifically to TAR. Previous
      circular dichroism (CD) experiments suggested that peptide binding induces a
      conformational change in TAR. Here we confirm this observation using single
      arginine-containing peptides and show that arginine or guanidine binding also
      induces a conformational change in TAR. A peptide containing a single arginine
      within a stretch of histidines (CYHHHRHHHHHA) shows pH-dependent binding and a
      corresponding change in TAR conformation, as detected by a decrease in the CD
      signal at 265 nm. Arginine and guanidine, which bind to TAR with apparent Kd's of
      approximately 1.5 mM, induce similar CD changes. In contrast, lysine, which does
      not bind specifically to TAR, has no effect. Mutants of TAR that abolish specific
      binding (a U-->C substitution in the three-nucleotide bulge, a deletion of the
      bulge, or an A-U to U-A base pair change above the bulge) show no change in the
      CD signal upon binding of peptides, arginine, or guanidine. The results suggest
      that binding of a single guanidinium group to a specific site in TAR induces a
      change in RNA conformation.

PMID- 1384696
TI  - Effects of pH on bacterial porin function.
AB  - Porin is a trimeric channel-forming protein in the outer membrane of Gram
      negative bacteria. Functions of the porins OmpF, OmpC, and PhoE from Escherichia
      coli K12 were analyzed at various pHs. Preliminary results from bilayer lipid
      membrane and liposome swelling assays indicated that in vitro porin has at least
      two open-channel configurations with a small and a large size. The small channels
      were stabilized at low pH while the larger channels were detected under basic
      conditions. The size switch occurred over a very narrow range near neutral pH,
      and the two major open-channel configurations responded differently to variations
      in voltage. The presence of two or more pH-dependent substates of porin could
      explain the variability in pore diameter measured by others and suggests a more
      dynamic role for porin in the cell.

PMID- 1384697
TI  - Involvement of histidine-21 in the pH-induced switch in porin channel size.
AB  - Porin is a channel-forming protein in the outer membrane of Gram-negative
      bacteria. In the previous paper (Todt et al., 1992), we showed that the pH
      induced a switch in the channel size in vitro for the porins OmpF, OmpC, and
      PhoE. In the results presented here, His21 of OmpC and OmpF from Escherichia coli
      was chemically modified with diethyl pyrocarbonate. Functional analysis of these
      modified porins at different pHs suggested that this histidine is involved in the
      pH-induced switch in channel size. Secondary structure analysis of porins at
      various pHs using Fourier transform infrared spectroscopy indicated that there
      was no global change in structure accompanying the pH-induced switch in channel
      size.

PMID- 1384698
TI  - Effect of antibody binding on protein motions studied by hydrogen-exchange
      labeling and two-dimensional NMR.
AB  - We have used hydrogen-exchange labeling detected by 2D NMR to study antibody
      protein interactions for two monoclonal antibodies raised against horse
      cytochrome c. The data show that these antibodies bind mainly to the large 37-59
      omega-loop of the cytochrome c molecule. In addition, the results provide some
      suggestive evidence concerning units of local structural flexibility in
      cytochrome c.

PMID- 1384699
TI  - Stereoelectronic factors in the interaction with DNA of small aromatic molecules
      substituted with a short cationic chain: importance of the polarity of the
      aromatic system of the molecule.
AB  - We have performed a quantitative analysis of the interaction with DNA of several
      unfused aromatic compounds synthesized in our laboratory and substituted with one
      or two short cationic chains. These and similar literature compounds, for which
      DNA binding data are available, bind with DNA by partial intercalation of the
      aromatic system, groove interaction of the linker chain, and groove electrostatic
      interactions of the terminal cationic group. Several independent quantitative and
      qualitative approaches show consistently that the strength of the interaction of
      the aromatic unit of the molecule with DNA binding sites depends on the direction
      and magnitude of polarity of the aromatic system. The phenomenon is explained in
      terms of the greatest negative potential in the DNA grooves, a concept
      extensively elaborated by Pullman and Pullman [cf. Lavery, R. and Pullman, B.
      [(1985) J. Biomol. Struct. Dyn. 2, 1021-1032] and references therein]. Classical,
      fused-ring planar intercalators do not follow the polarity-DNA affinity
      correlation, presumably because the intercalative forces depend more strongly on
      polarizability than on polarity of the aromatic system.

PMID- 1384701
TI  - Methylation sites in Escherichia coli ribosomal RNA: localization and
      identification of four new sites of methylation in 23S rRNA.
AB  - Four previously undetermined sites of methylation are mapped in Escherichia coli
      23S rRNA employing a novel combination of methods. First, using a double-isotope
      approach, the total number of methyl groups in 23S rRNA was determined to be 14.9
      +/- 1.6. Second, hybridization of methyl-labeled rRNA to complementary DNA
      restriction fragments and PAGE analysis were used to purify RNA-DNA
      heteroduplexes and to quantify methyl groups within specific 23S rRNA fragments.
      Third, the methylated nucleosides in these fragments were identified and
      quantified using HPLC, confirming the presence of 14 methylation sites in 23S
      rRNA, four more than had been previously identified. In contrast, a similar set
      of analyses conducted on 16S rRNA gave evidence for 10 sites of methylation, at
      all approximate locations consistent with published 16S methylated nucleoside
      identities and locations. Selected regions of the 23S rRNA molecule containing
      previously unidentified methylated nucleosides were released by site-directed
      cleavage with ribonuclease H and isolated by PAGE. Sites of methylation within
      the RNA fragments were determined by classical oligonucleotide analyses. The four
      newly identified methylation sites in 23S rRNA are m2G-1835, m5C-1962, m6A-2503,
      and m2G at one of positions 2445-2447. Together with previously described sites
      of modification, these new sites form a group that is clustered in a current
      model for the three-dimensional organization of the 23S rRNA in the 50S ribosomal
      subunit, at a locus congruent with nucleotides previously implicated in ribosomal
      function.

PMID- 1384700
TI  - Endonucleolytic cleavage of a long 3'-trailer sequence in a nuclear yeast
      suppressor tRNA.
AB  - Transcripts of Saccharomyces cerevisiae nuclear tRNA genes are normally
      terminated within a few nucleotides of the tRNA coding region, in contrast to
      mitochondrially encoded tRNAs, which are contained within polycistronic
      transcripts and thus require 3'-processing by mitochondrial endonucleases. We
      show that 3'-processing activities capable of removing artificially extended 3'
      trailer sequences from some tRNA substrates are also present in the yeast
      nucleus. Correct 3'-processing in vivo resulted in the formation of functional
      suppressor tRNA. The 3'-processing activities were also identified in vitro
      through analysis of transcription-processing products in cell-free yeast S-100
      extracts. Comparison of several pre-tRNA substrates showed that the tRNA
      structure played a major role in determining the processability of a substrate
      but that the nature of the 3'-trailer sequence also modulated the rate of 3'
      processing. Pre-tRNA containing mitochondrial tRNA(Val) sequence was a good
      substrate for in vitro processing, independent of its 3'-trailer. A 200-nt-long
      pre-tRNA, encoding the nuclear SUP4 tRNA gene and a mitochondrial 3'-trailer, was
      processed in yeast S-100 extract in a multistep pathway into mature-sized
      tRNA(Tyr). Part of the 3'-processing was due to an endonuclease which cleaved
      near or precisely at the 3'-end of the coding region of the tRNA. A short
      sequence around this endonucleolytic 3'-cleavage site was crucial for the
      formation of active suppressor tRNA in vivo. A 9-nt-long sequence motif derived
      from the mitochondrial 3'-trailer allowed processing, while sequences derived
      from lacZ or pBR322 DNA were processed neither in vitro nor in vivo.

PMID- 1384702
TI  - Characterization of baculovirus-expressed human alpha and beta platelet-derived
      growth factor receptors.
AB  - In an effort to biochemically characterize PDGF receptors and their mechanism of
      activation, recombinant baculovirus vectors containing the cDNAs of the human
      alpha PDGF receptor or beta PDGF receptor were engineered. Characterization of
      recombinant PDGF receptor expression in infected Sf9 insect cells by immunoblot
      analysis with specific PDGF receptor peptide antisera revealed that the alpha and
      beta PDGF receptor gene products were translated as 160- and 165-kDa
      transmembrane proteins, respectively. Ligand binding analysis demonstrated
      saturable, high-affinity binding of either 125I-labeled PDGF AA or 125I-labeled
      PDGF BB to Sf9 cells expressing the recombinant alpha PDGF receptor. In contrast,
      recombinant beta PDGF receptor expressing Sf9 cells showed high-affinity binding
      only for PDGF BB. Analysis of the kinetics of PDGF receptor expression
      demonstrated that receptor number increased dramatically from 24- to 48-h
      postinfection. Early in infection, the PDGF receptors were present in low
      numbers, lacked tyrosine phosphorylation, and exhibited ligand-dependent tyrosine
      phosphorylation. However, with increasing time postinfection and increasing
      receptor number, the PDGF receptors became constitutively tyrosine-phosphorylated
      in serum-free culture medium. Cross-linking studies revealed that receptor
      activation involved ligand-independent receptor dimer formation at high receptor
      number. Thus, these results strongly suggest that PDGF stabilizes and increases
      the frequency of PDGF receptor interaction, which ultimately results in PDGF
      receptor activation and intracellular signaling.

PMID- 1384703
TI  - Expression of cell adhesion molecules in human cardiac allograft rejection.
AB  - Adhesion of leukocytes to vascular endothelial cells is a critical step in a
      variety of inflammatory conditions. We studied the expression and distribution of
      intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion
      molecule-1 (ELAM-1) in frozen sections of 83 endomyocardial biopsy specimens from
      human allograft hearts using monoclonal antibodies and an avidin-biotin complex
      alkaline phosphatase staining technique. Cases with cellular or humoral rejection
      and Quilty lesions were studied. Staining was graded from 0 to 3+ in lymphocytes
      and in capillary, arterial, venular, and endocardial endothelial cells.
      Expression of ICAM-1 in capillaries increased with the severity of cellular
      rejection and was prominent in humoral rejection. ICAM-1 was also expressed in
      lymphocytes in proportion to the degree of rejection. Little or no ELAM-1
      expression was noted. In Quilty lesions the intensity of ICAM-1 expression was
      similar to that of mild-to-moderate rejection. Thus adhesion molecule expression
      can be identified in endomyocardial biopsy specimens of patients with rejection,
      suggesting a role for adhesion molecules in the process of rejection. These
      findings may prove useful in monitoring rejection and its response to therapy and
      in developing specific antisera directed against these molecules.

PMID- 1384704
TI  - Expression of amiloride-sensitive Na+ channels of hen lower intestine in Xenopus
      oocytes: electrophysiological studies on the dependence of varying NaCl intake.
AB  - Epithelial Na+ channels were incorporated into the plasma membrane of Xenopus
      laevis oocytes after micro-injection of RNA from hen lower intestinal epithelium
      (colon and coprodeum). The animals were fed either a normal poultry food which
      contained NaCl (HS), or a similar food devoid of NaCl (LS). Oocytes were
      monitored for the expression of amiloride-sensitive sodium channels by measuring
      membrane potentials and currents. Oocytes injected with poly(A)+RNA prepared from
      HS animals or non-injected control oocytes showed no detectable sodium currents,
      whereas oocytes injected with LS-poly(A)+RNA had large amiloride-blockable sodium
      currents. These currents were almost completely saturated by sodium
      concentrations of 20 mM with a Km of about 2.6 mM sodium. Amiloride (10 microM)
      inhibits the expressed sodium channels entirely and examination of dose response
      relationships yielded a half-maximal inhibition concentration (Ki) of 120 nM
      amiloride. I-V difference curves in the presence or absence of sodium or
      amiloride (10 microM) indicate a potential dependence of the sodium transport
      which can be described by the Goldman equation. When Na+ is replaced by K+, no
      amiloride response was detected indicating a high selectivity for Na+ over K+.
      These results provide strong evidence that intestinal Na+ channels are regulated
      by dietary salt intake on the RNA level.

PMID- 1384705
TI  - Induction of two K+ currents by complement component C5a in mouse macrophages.
AB  - Puff application of complement component C5a (5 x 10(-8) M) onto peritoneal
      macrophages from thioglycollate-stimulated mice induced two kinds of outward
      current at a holding potential of -68 mV, a slowly-rising sustained outward
      current and a spike-like transient outward current. Quinidine (2 x 10(-4) M) and
      tetraethylammonium (10(-2) M) partially suppressed both types of outward current.
      Charybdotoxin (2 x 10(-6) M) markedly suppressed the spike-like outward current.
      Reversal potentials in bath solutions of different external K+ concentrations
      were dependent only on K+ concentrations. The transient current was not
      suppressed in Ca(2+)-free EGTA-containing solution, but was completely abolished
      in BAPTA-containing solution. One kind of single channel responding to C5a, which
      has a single-channel conductance of 29 pS, was recorded from cell-attached
      patches. These results suggest that C5a activates a Ca(2+)-dependent and another
      type of K+ current.

PMID- 1384706
TI  - Interaction of melittin derivatives with lipid bilayer membrane. Role of basic
      residues at the C-terminal and their replacement with lactose.
AB  - Melittin possesses an amphiphilic property in the primary sequence in which
      hydrophilic residues are located at the C-terminal region from Lys-21 to Gln-26.
      A part of the hydrophilic sequence was cleaved off by endopeptidase Arg-C to
      obtain melittin 1-22. The affinity of melittin 1-22 for neutral phospholipid
      membrane was reduced to 1/3 that of melittin, indicating that the basic residues,
      Lys-23 and Arg-24, are important in binding of melittin to the membrane. The
      melittin 1-22 was extended toward the C-terminal end by connection of lactose
      (melittin-lac), the membrane affinity of which was slightly higher than the
      melittin 1-22, but lower than melittin. The leakage experiment of 5,6
      carboxyfluorescein encapsulated in DPPC liposomes showed that the activities of
      melittin 1-22 and melittin-lac in membrane lysis were much lower than melittin.
      However, the melittin 1-22 formed a voltage-dependent ion-channel in an azolectin
      bilayer membrane. It is thus considered that Lys-23 and Arg-24 residues of
      melittin play an important role in binding to the polar region of membrane for
      lysis, but not for ion-channel formation.

PMID- 1384707
TI  - Modulation by glycosphingolipids of membrane-membrane interactions induced by
      myelin basic protein and melittin.
AB  - The effect of glycosphingolipids (GSLs) with oligosaccharide chains of different
      length and charge on membrane-membrane interactions induced by myelin basic
      protein (MBP) or melittin (Mel) was comparatively investigated with small
      unilamellar vesicles. MBP induces a fast vesicle aggregation and close membrane
      apposition. Merging of lipid bilayers and vesicle fusion induced by MBP are
      slower and less extensive processes compared to membrane apposition. The changes
      of membrane permeability concomitant to these phenomena are small. The Trp region
      of MBP remains in a rather polar environment when interacting with vesicles; its
      accessibility to NO3- or acrylamide quenching depends on the type of GSLs in the
      membrane. The Trp region of Mel is inserted more deeply into the lipid bilayer
      and its accessibility to the aqueous quenchers is less dependent on variations of
      the oligosaccharide chain of the GSLs. Mel induces a faster and more extensive
      membrane apposition and bilayer merging than does MBP. Extensive vesicle
      disruption occurs in the presence of Mel. Negatively charged GSLs facilitate
      membrane proximity and vesicle aggregation but an increase of the oligosaccharide
      chain length of either neutral or acidic GSLs decreases the interaction among
      vesicles that are induced by either protein. This effect is independent of the
      different mode of insertion of MBP and Mel into the membrane. Our results suggest
      that the modulation by the oligosaccharide chain on the protein-induced
      interactions between bilayers containing GSLs is probably exerted beyond the
      level of local molecular interactions between the basic proteins and the lipids.

PMID- 1384708
TI  - A patch-clamp study of Bacillus subtilis.
AB  - In patch-clamp experiments on giant protoplasts of the Gram-positive bacterium
      Bacillus subtilis, membrane stretch resulted in an initial transient collapse of
      the membrane resistance, after which stretch-activated, voltage modulated, high
      conductance channels could be observed. The channel open probability increased
      exponentially with applied suction and positive voltage, as a result of
      variations of both the mean open and the mean closed times. The substate
      structure and other characteristics of the electrical activity suggested the
      presence of a family of pores exhibiting cooperative behavior. A role in osmotic
      protection is suggested. In the intact bacteria, the pores may be part of an
      unidentified envelope apparatus, having other functions as well.

PMID- 1384709
TI  - Development of a procedure for coupling the homing device glu-plasminogen to
      liposomes.
AB  - The aim of this study was to find a suitable way of coupling the homing-device
      glu-plasminogen to the outside of liposomes. The described procedure is based on
      the reaction of thiol-groups introduced in the protein with thiol-reactive groups
      of the liposome. Details on the thiolation of proteins with the reagent
      succinimidyl-S-acetylthioacetate (SATA) were studied for a model-protein,
      amylase. Increasing the incubation-ratio SATA: amylase resulted in a gradually
      growing number of introduced thiol-groups, until a maximum of about 5 mol SH per
      mol amylase was reached. The enzymatic activity of the derivatized protein was
      even higher than that of native amylase. The thiol-introduction was then applied
      to glu-plasminogen itself. After activation with SATA, the protein was incubated
      with liposomes containing the thiol-reactive anchor maleimido-4-(p
      phenylbutyrate)-phosphatidylethanolamine (MPB-PE). Under the chosen conditions,
      incubation of 0.5-2.5 mg/ml protein with 6.0-7.5 mumol/ml phospholipid for 30-120
      min resulted in coupling-ratios of 20 to 94 micrograms glu-plasminogen per mumol
      phospholipid. This corresponds with about 140 to 660 protein molecules per
      liposome. SATA-derivatization of glu-plasminogen brought about a loss of its
      enzymatic activity induced by streptokinase. This activity of liposomally coupled
      plasminogen was about 52 to 74% of the activity of native glu-plasminogen
      (depending on the coupling-ratio). Although this may seem a significant loss of
      activity, it was shown that the capacity of liposomal glu-plasminogen to bind to
      its target, fibrin, was not reduced but several fold higher under the used
      conditions than that of the free protein. Therefore, the described method for
      thiol-introduction is an effective way to thiolate amylase without loss of
      activity, and to bind the homing-device glu-plasminogen to liposomes without
      substantially interfering with its fibrin-binding/homing capacity.

PMID- 1384711
TI  - Transfer RNA genes from the hyperthermophilic Archaeon, Methanopyrus kandleri.
AB  - Genes encoding the Leu (GAG), Ser (UGA), Gln (UUG) and Lys (UUU) tRNAs have been
      cloned and sequenced from the deep sea hyperthermophilic Archaeon, Methanopyrus
      kandleri. Sequences conforming to the TATA box element established for methanogen
      promoters are located upstream of the tRNA(Gln) and tRNA(Lys) genes. All four of
      the tRNA genes appear to encode the 3' terminal CCA residues of the mature tRNA.
      These methanogen tRNAs are predicted to contain most, but not all, invariant
      residues and are characterized by a high level of G + C base pairing, consistent
      with the 98 degrees C optimum growth temperature of M. kandleri.

PMID- 1384710
TI  - Binding of a monoclonal antibody E12 to Gc globulin (vitamin D-binding protein)
      is inhibited by actin.
AB  - A monoclonal antibody, E12, to human Gc globulin was raised in murine somatic
      cell using purified Gc. The antibody was subtyped IgG2b kappa and had a kd of 3.0
      x 10(-8) M for antigen Gc. Monospecificity for Gc was demonstrated by Western
      blotting of normal human serum using nondenaturing polyacrylamide gel
      electrophoresis. As judged by ELISA, actin inhibited binding of E12 to Gc in dose
      dependent fashion. Affinity chromatography studies further showed that ternary
      complexes of actin-Gc-E12 were not formed, and actin displaced Gc from Gc-E12
      complexes. Proteolytic digestion of Gc with trypsin showed that the monoclonal
      antibody E12 reacted with the major 30-kDa tryptic fragment containing the amino
      terminal fragment of Gc, but actin did not react with this fragment. These
      results indicate that interaction of actin with Gc causes conformational changes
      which inhibit binding of E12.

PMID- 1384712
TI  - Excessive production of transforming growth-factor beta 1 can play an important
      role in the development of tumorigenesis by its action for angiogenesis: validity
      of neutralizing antibodies to block tumor growth.
AB  - Angiogenesis is an important part of tumor growth in vivo. We used the
      transfected Chinese hamster ovary (CHO) cells that overproduced recombinant
      transforming growth-factor beta 1 (TGF-beta 1) to examine the possible role of
      this factor in tumor growth and angiogenesis in a nude mouse model. The in-vitro
      proliferation of TGF-beta 1-transfected CHO cells was unaffected by the treatment
      of either recombinant TGF-beta 1 or an anti-TGF-beta 1 antibody. The TGF-beta 1
      transfected cells grew more rapidly than the parental CHO cells when injected
      subcutaneously into nude mice. The tumors derived from the TGF-beta 1-transfected
      cells showed prominent tumor-associated angiogenesis, whereas the parental cells
      produced tumors without such angiogenesis. In addition, an anti-TGF-beta 1
      neutralizing antibody was able to inhibit both growth and angiogenesis in the
      tumors derived from TGF-beta 1-transfected cells. These findings suggest that the
      overproduction of TGF-beta 1 by tumor cells can contribute to neovascularization
      and may help promote tumor development in vivo.

PMID- 1384713
TI  - Purification of an active receptor for acidic and basic fibroblast growth factor
      from bovine retina.
AB  - Acidic and basic fibroblast growth factors (FGFs) influence cell division and
      differentiation in retina cells. Their effects are thought to be mainly mediated
      through stimulation of a specific membrane receptor and subsequent generation of
      an intracellular signal pathway. In this study, we purified a FGF receptor of 130
      kDa from bovine neural retina using wheat germ agglutinin affinity chromatography
      followed by FGF-affinity chromatography. The isolated receptor showed ligand
      binding activity with dissociation constants of 0.8 nM and 2 nM for aFGF and
      bFGF, respectively. Furthermore, binding of aFGF and bFGF to purified receptor
      resulted in self-phosphorylation, demonstrating that the isolated receptor had an
      unaltered intrinsic kinase activity.

PMID- 1384715
TI  - Regulation of lipoprotein lipase by dibutyryl cAMP, cholera toxin, Hepes and
      heparin in F1 heart-cell cultures.
AB  - Regulation of lipoprotein lipase was studied in mesenchymal rat heart-cell
      cultures. Treatment of the cultures with dibutyryl cyclic AMP or with cholera
      toxin resulted in an increase in LPL activity and a comparable increase in LPL
      mRNA. When the cells were exposed to 100 mM Hepes for 24 h, total enzyme activity
      rose 2-fold and LPL mRNA increased 2.4-fold. After 72 h, there was a 3-fold
      increase in LPL mRNA and a 4-fold rise in cellular LPL activity, while medium
      activity increased 20-fold. Exposure of the cultures to heparin for 24 h resulted
      in a 3.2-fold increase in total activity and a 36-fold increase in medium
      activity. This increase was not accompanied by any rise in LPL mRNA. Addition of
      actinomycin D to control dishes for 24 h resulted in a 33% reduction in LPL mRNA
      and a 43% reduction in enzyme activity. These values were 71% and 56%,
      respectively, in Hepes-treated cells, indicating that no stabilization of LPL
      mRNA occurred under these conditions. It can be concluded that in mesenchymal rat
      heart-cells in culture cAMP and cholera toxin upregulate lipoprotein lipase at
      the level of transcription. The increase in LPL activity after 24 h exposure to
      Hepes could be compatible with transcriptional regulation, while exposure to
      heparin is not accompanied by a change in LPL mRNA.

PMID- 1384714
TI  - Rapid regulation of albumin transcription by insulin and phorbol esters in rat
      hepatoma cells.
AB  - The short-term effects of insulin and phorbol esters on the regulation of the
      albumin gene in rat H4IIE (H4) hepatoma cells were investigated and compared to
      the expression of a gene known to be inhibited by these agents, phosphoenol
      pyruvate carboxykinase (PEPCK). Both insulin and phorbol esters inhibited
      transcription of the albumin gene in a rapid, dose-dependent manner. Within 15
      min, albumin transcription was reduced by approx. 80%. The inhibitory effects of
      insulin were evident at concentrations of insulin as low as 5.10(-11)M,
      suggesting that these effects were mediated through insulin-specific pathways.
      The ability of both phorbol esters and insulin to inhibit albumin transcription
      suggests that the negative control of this gene is a stable feature in H4 cells.
      The effect of phorbol esters to mimic insulin action on the albumin gene, and on
      several other genes in this cell line, implies that a common pathway may be
      shared by both insulin and phorbol esters.

PMID- 1384716
TI  - The pathology of the neuronal cytoskeleton in Alzheimer's disease.
AB  - The two characteristic neuropathological lesions of Alzheimer's disease are the
      neurofibrillary tangles and the senile plaques. Neurofibrillary tangles are made
      of abnormal filaments (PHF) accumulating in neurons and mainly composed of a
      modified form of the microtubule-associated protein tau (PHF-tau). Senile plaques
      are composed of a cluster of dystrophic neurites surrounding an extracellular
      deposit of amyloid fibers made of a 42 amino-acid peptide (beta-amyloid peptide).
      The abnormal filaments contain the complete sequences of the different tau
      isoforms. The PHF-tau proteins can be distinguished from the normal tau proteins
      by the presence of several phosphorylated sites. One of these sites is
      phosphorylated by a calcium-calmodulin-dependent kinase. The relationship between
      PHF-tau and the cytoskeletal pathology in Alzheimer's disease is further
      discussed.

PMID- 1384717
TI  - cDNA sequence of the small subunit of the hamster ribonucleotide reductase.
AB  - Ribonucleotide reductase activity is markedly elevated in cell lines selected for
      resistance to hydroxyurea, a cytotoxic drug known specifically to inhibit
      ribonucleotide reductase. From a cDNA library constructed from a highly
      hydroxyurea-resistant hamster lung cell line, 600H in which the activity is
      elevated more than 80-fold, we have isolated a full length cDNA for the small
      subunit of the reductase. The cDNA is 3.48 kb long with an open reading frame of
      1158 nucleotides and a long 3' flanking region of 2169 nucleotides from the
      termination codon. The derived polypeptide sequence is closely similar to the
      small subunit of the mouse, differing from it in 20 amino acid positions. Most of
      these replacements occur in the N-terminal segment of the protein. The hamster
      subunit does not contain 4 amino acid residues found in the mouse small subunit
      near the C-terminal end. RNA blots probed with the cDNA show two poly(A)+ RNA
      species which are elevated in hydroxyurea-resistant cells.

PMID- 1384718
TI  - Identification of an abundant monkey epididymal transcript encoding a homologue
      of human CAMPATH-1 antigen precursor.
AB  - A number of cDNA clones encoding a small (0.5-0.6 kb) transcript have been
      isolated from a monkey (Macaca fascicularis) epididymal cDNA library. DNA
      sequence analysis indicates that this abundant epididymal transcript is
      homologous to the human CAMPATH-1 (CDw52) antigen precursor, a GPI-anchored
      membrane glycoprotein previously described on lymphocytes and monocytes.

PMID- 1384719
TI  - Interferon production of L929 and HeLa cells enhanced by polyriboinosinic acid
      polyribocytidylic acid pH-sensitive liposomes.
AB  - The double-stranded RNA polyinosinic acid-polycytidylic acid (PolyIC) is an
      inducer of interferons alpha and beta (IFN) genes. With L929 and HeLa cells IFN
      pretreatment (priming) improves the IFN induction by PolyIC by several orders of
      magnitude. In the absence of the priming we demonstrate that PolyIC encapsulated
      into pH-sensitive liposomes (and not into pH-insensitive liposomes) enables L929
      cells to secrete IFN efficiently and a low toxicity is observed; on primed cells
      pH-sensitive liposomes containing PolyIC trigger a high toxicity. With HeLa
      cells, the absence of the priming PolyIC encapsulated into pH-sensitive liposomes
      induces weak doses of IFN whereas free PolyIC was ineffective. Our experiments
      established that a pH drop (from 8 to 5.5) provoked a lipid mixing between pH
      sensitive liposomes and cell membranes, likely by a fusion mechanism. Entrapment
      into pH-sensitive liposomes enhances the effect of PolyIC by several orders of
      magnitude, which might improve its therapeutic ability as an antitumor or anti
      HIV agent.

PMID- 1384720
TI  - The p60c-src family of protein-tyrosine kinases: structure, regulation, and
      function.
AB  - In 1911, Peyton Rous reported that a fibrosarcoma could be transmitted between
      chickens in a cell-free extract of the tumor. The transmissible agent, Rous
      sarcoma virus (RSV), transforms cells by virtue of the presence within its genome
      of a viral oncogene, v-src, which is derived from a normal cellular gene that has
      been picked up, or transduced, by the virus. This cellular proto-oncogene, c-src,
      encodes a protein, p60c-src, which has the ability to phosphorylate proteins on
      tyrosine residues. Studies of RSV were thus directly responsible for the
      discovery of cellular proto-oncogenes and of protein-tyrosine kinases,
      discoveries which have been fundamental in shaping our ideas about cellular
      growth control. In spite of this, the normal biological role of p60c-src is still
      unclear and it remains impossible to provide a full answer to the question of how
      RSV causes tumors. It is clear, however, that c-src is the prototype of a family
      of at least 8 closely related genes encoding protein tyrosine kinases, the other
      family members being blk, c-fgr, fyn, hck, lck, lyn, and c-yes. The purpose of
      this review is to outline our current knowledge of the structure, expression
      pattern, and function of each of the members of the c-src gene family and to
      describe recent data which begins to explain how these proteins interact with
      other cellular proteins to control cell behavior. The evidence for involvement of
      these proteins in oncogenesis is also discussed.

PMID- 1384721
TI  - Adhesion molecules on CD34+ hematopoietic cells in normal human bone marrow and
      leukemia.
AB  - Expression of selected adhesion molecules of the integrin and immunoglobulin
      family was investigated on CD34+ leukemic cells in 19 AML and 11 ALL cases to
      evaluate phenotypic differences in adhesive properties of malignant hematopoietic
      precursor cells in comparison to normal bone marrow CD34+ cells. Of the beta 2
      integrin family, CD11a was expressed on > 50% of CD34+ cells in normal bone
      marrow and almost all leukemias, whereas CD11b and CD11c were not expressed on
      CD34+ cells in normal bone marrow, but were found on CD34+ blasts in some
      leukemias of a heterogeneous immunophenotype. Of the beta 1-family, CDw49d (VLA
      4) was strongly expressed on normal CD34+ bone marrow cells and on the blasts of
      all 30 CD34+ leukemic samples, whereas CDw49b (VLA-2) was absent on CD34+ cells
      in normal bone marrow, but detected on CD34+ cells in a few leukemias which did
      not constitute a clinical or phenotypic entity according to the FAB
      classification or immunocytological analysis. The lymphocyte-homing-associated
      adhesion molecule CD44 (HCAM) and CD58 (LFA-3) were expressed on CD34+ cells in
      all investigated cases of normal and leukemic bone marrow. ICAM-1 (CD54), the
      inducible receptor ligand for CD11a/CD18, although present on CD34+ cells in
      normal bone marrow, was lacking on blast cells of some ALL and AML cases. So far,
      the variable expression of beta 2-integrins as well as of VLA-2 and of ICAM-1
      could indicate distinct differences in cell-cell or cell-matrix adhesion of
      leukemic cells in ALL and AML patients.

PMID- 1384722
TI  - Successful second allogeneic bone marrow transplantation in a relapsed acute
      myeloid leukemia patient with fungal liver abscess.
AB  - Disseminated fungal infection not infrequently complicates the course of
      allogeneic bone marrow transplantation (allo BMT) in severely immunocompromised
      patients, and the prognosis of BMT patients who develop systemic fungal infection
      is very poor. We describe a patient who developed disseminated Candida albicans
      infection with liver abscess after the first allo BMT for acute myelogenous
      leukemia (FAB M2). The infection was successfully eradicated by the
      administration of miconazole and amphotericin B. However, 1 year after the first
      allo BMT, the patient suffered a relapse of acute myelogenous leukemia with
      fungal liver abscess. A second allo BMT, accelerating granulocyte recovery by
      recombinant human granulocyte colony-stimulating factor (rhG-CSF), was
      successfully performed and the fungal liver abscess resolved with a combination
      therapy of fluconazole and amphotericin B. The patient is alive and free of both
      leukemia and fungal disease more than 37 months after the first allo BMT and 25
      months after the second allo BMT.

PMID- 1384723
TI  - Prevention of estrus in the queen with chlormadinone acetate administered orally.
AB  - The possibility of estrus prevention in the queen by the oral administration of
      chlormadinone acetate was examined. The animals used were 29 mature and 15
      immature queens. For 16 mature females, 4-12.5 mg was given daily by mouth for 7
      days every 3 months. Ten of the 16 queens given this treatment came into estrus
      within 4 months of the first treatment. For 28 females including the immature, 2
      12.5 mg was given once a week throughout the experiment. This treatment prevented
      estrous activity for at least 1 year. In the queens in this study, the side
      effects were not observed excepting an increase in body weight during treatment.
      Our results showed that oral administration of this drug weekly is safe and
      reliable for long-range prevention of estrus in queens.

PMID- 1384724
TI  - On the fine structure and complex carbohydrate cytochemistry of the rabbit
      parotid gland.
AB  - The parotid gland of the rabbit, a lagomorph species, was studied by
      ultrastructural techniques and carbohydrate ultracytochemical stainings. The
      rabbit parotid gland is a peculiar mixed gland consisting of serous and mucous
      secretory cells due to their histochemical properties supported by biochemical
      findings. Acinar cells exhibit heterogeneous features of secretory granules with
      different electrondensity and occasional presence of subunits. Intercalated duct
      cells show nuclei with deep indentation and apical granules partly similar to
      acinar secretory products. Striated ducts are characterized by three different
      cell populations, namely "light cells" with small secretory granules, "dark
      cells" rich of scattered mitochondria and typical striated cells. The presence of
      differentiated cell types within striated duct segments lends credence to the
      idea that, in addition to the role in electrolyte transport, some ductal cells
      may be involved in secretion and/or absorption of glycosylated products.

PMID- 1384725
TI  - A longitudinal assessment of CSF monoamine metabolite and plasma cortisol
      concentrations in young rhesus monkeys.
AB  - Twenty-two rhesus macaques were studied longitudinally from infancy to early
      adolescence in order to assess the effects of developmental change, experimental
      history, gender, and individual variation on the response of the
      catecholaminergic, serotonergic, and adrenocortical systems to separation-induced
      stress. Experimental effects were assessed by comparing subjects reared for the
      first 6 months of life either with their mothers or in peer groups. Developmental
      changes in response to repeated separation stress were assessed by subjecting the
      monkeys to four sequential 4-day social separations when they were 6 and 18
      months old. At both ages, prior to, and on the last day of the first and fourth
      separations, cerebrospinal fluid (CSF) was obtained from the cisterna magna to
      assess monoamine metabolite concentrations, and blood samples were collected to
      assess plasma cortisol concentrations. Blood samples were also obtained on the
      first day of each separation at each age. Age-related declines were found in both
      homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations
      for all subjects. Social separation consistently increased CSF 3-methoxy-4
      hydroxyphenolglycol (MHPG) over baseline levels, but decreased HVA
      concentrations, whereas 5-HIAA levels increased following the first, but not the
      fourth separation. Plasma cortisol increased rapidly immediately after separation
      and remained higher than baseline on day 4 of both the first and fourth
      separation. Independent of age and experimental condition, peer-rearing increased
      CSF MHPG and plasma cortisol concentrations. During year 1, peer-rearing also
      produced diminished CSF 5-HIAA concentrations in female monkeys relative to
      female mother-reared monkeys, but increased male peer-reared monkeys'
      concentrations relative to mother-reared males. Interindividual differences were
      highly stable, with significant correlations both within and between years for
      each of the three metabolites and cortisol.

PMID- 1384726
TI  - The clinical relevance of salivary amylase monitoring in bulimia nervosa.
AB  - The aim of this study was to evaluate the clinical relevance of amylase level
      monitoring as an objective measure in diagnosis and assessment of treatment
      response in bulimia nervosa. Thirty-three subjects who fulfilled DSM-111-R
      criteria for bulimia nervosa had serum levels of total and salivary amylase
      monitored during an 8-week treatment trial. At the beginning of treatment, the
      average total amylase level was within the upper limits of normal, whereas
      average salivary amylase levels were abnormally high. During the course of
      treatment, there was a significant reduction in the average salivary isoenzyme to
      within the normal range. Significant reductions in amylase levels were recorded
      in patients with good treatment outcome, but not in those with poor outcome.
      Amylase levels were not significantly correlated with severity of bulimic
      symptoms. These results do not justify the use of amylase assays as a routine
      diagnostic or monitoring test, but isoenzyme monitoring may provide useful
      clinical information in selected cases.

PMID- 1384727
TI  - Serotonin receptor sensitivity and suicide.

PMID- 1384728
TI  - Biogenic amine metabolites in plasma of drug-naive schizophrenic patients:
      associations with symptomatology.
AB  - The main metabolites of dopamine, noradrenaline, and serotonin, homovanillic
      acid, methoxyhydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA),
      were estimated in plasma of 20 drug-naive young male schizophrenic patients and
      21 healthy controls. Although there were no significant differences between the
      two groups, multiple regression analysis revealed strong associations of the
      patients' 5-HIAA and MHPG plasma levels to their scores in the Brief Psychiatric
      Rating Scale items. 5-HIAA levels were mainly related positively to hostility and
      negatively to somatic concern, and MHPG positively to disorientation and
      negatively to emotional withdrawal and uncooperativeness. The results suggest
      that levels of the neurotransmitter metabolites may be related to certain
      psychological dysfunctions of the patients rather than to disease entities.

PMID- 1384729
TI  - Metronidazole and pancreatitis.

PMID- 1384730
TI  - [Flagellate pigmented erythema secondary to bleomycin for scrape injuries].

PMID- 1384731
TI  - Proliferative responses of peripheral blood mononuclear cells from patients with
      autoimmune thyroid diseases to synthetic peptide epitopes of human thyroid
      peroxidase.
AB  - In order to analyze T cell epitopes of human thyroid peroxidase (TPO), 60
      peptides based on the sequence of TPO were synthesized and used as antigens in a
      peripheral blood mononuclear cell (PBMC)-proliferation assay. PBMCs were obtained
      from 19 patients with Graves' disease, 19 patients with Hashimoto's thyroiditis,
      and 24 normal subjects. Significant proliferation of PBMC to these peptides
      occurred only among the autoimmune thyroid disease (AITD) patients, whereas
      normal subjects did not respond to any of the peptides with a stimulation index
      over 2. Many peptides induced isolated positive responses and eight produced
      stimulation of PBMCs from multiple patients on comparison to control PBMC
      responses. To confirm the significance of reactivity to the peptides PBMCs from
      four patients were studied on two occasions, and the proliferative responses
      found to be reproducible. Four peptides, designated according to the amino acid
      sequence as p110-129, p211-230, p842-861, and p882-901, stimulated patients'
      PBMCs in a dose-dependent manner. The optimal concentration was 10 micrograms/ml.
      An anti-HLA-DR monoclonal antibody directed against a monomorphic determinant of
      the DR molecule was able to block the responses. A significant correlation was
      found between the PBMC responses to these peptides and responses to microsomal
      antigen (McAg)/TPO. These data suggest that four peptides corresponding to the
      amino acid sequences 110-129, 211-230, 842-861 and 882-901 are T cell epitopes of
      TPO.

PMID- 1384732
TI  - The role of the cancer registry in cancer control.
AB  - It has been accepted generally that the cancer registry has more of a 'back room'
      than a 'front line' role in cancer control, its particular responsibilities lying
      in description of cancer patterns, care, and outcome, in monitoring these
      variables in relation to control activities, and in providing a research database
      -often, for others to utilize. While readily justifiable, this prevailing concept
      of the cancer registry's role may not be sustainable in times of economic
      restraint. A survey of members of the International Association of Cancer
      Registries showed that most registries fit the accepted mold. Some, however,
      extend beyond it, particularly in the direct conduct of epidemiologic research
      and in the implementation of control programs, particularly screening. Sixteen
      percent appeared only to be collecting incidence statistics and may be at risk of
      economic rationalization. It would be consonant with their basic role and skills,
      and promote more rational cancer control, if cancer registries were to take on an
      expanded role, including direct participation in epidemiologic research,
      evaluation of interventions against cancer at the population level, situation
      analysis and cancer control planning, and implementation of aspects of cancer
      control--particularly coordination of screening--and monitoring the performance
      of cancer control programs. This expanded role could become the responsibility of
      specialized cancer control units of which cancer registration would be the
      central function.

PMID- 1384733
TI  - Gramicidin channel selectivity. Molecular mechanics calculations for
      formamidinium, guanidinium, and acetamidinium.
AB  - Empirical energy function calculations were used to evaluate the effects of
      minimization on the structure of a gramicidin A channel and to analyze the
      energies of interaction between three cations (guanidinium, acetamidinium,
      formamidinium) and the channel as a function of position along the channel axis.
      The energy minimized model of the gramicidin channel, which was based on the
      results of Venkatachalam and Urry (1983), has a constriction at the channel
      entrance. If the channel is not allowed to relax in the presence of the ions
      (rigid model), there is a large potential energy barrier for all three cations.
      The barrier varies with cation size and is due to high van der Waals and ion
      deformation energies. If the channel is minimized in the presence of the ions,
      the potential energy barrier to formamidinium entry is almost eliminated, but a
      residual barrier remains for guanidinium and acetamidinium. The residual barrier
      is primarily due, not to the expansion of the helix, but, to the disruption of
      hydrogen bonds between the terminal ethanoloamine and the next turn of the helix
      which occurs when the carbonyls of the outer turn of the helix librate inward
      toward the ion as it enters the channel. The residual potential energy barriers
      could be a possible explanation for the measured selectivity of gramicidin for
      formamidinium over guanidinium. The results of this full-atomic model address the
      applicability of the size-exclusion concept for the selectivity of the gramicidin
      channel.

PMID- 1384734
TI  - Simulation of cell rolling and adhesion on surfaces in shear flow: general
      results and analysis of selectin-mediated neutrophil adhesion.
AB  - The receptor-mediated adhesion of cells to ligand-coated surfaces in viscous
      shear flow is an important step in many physiological processes, such as the
      neutrophil-mediated inflammatory response, lymphocyte homing, and tumor cell
      metastasis. This paper describes a calculational method which simulates the
      interaction of a single cell with a ligand-coated surface under flow. The cell is
      idealized as a microvilli-coated hard sphere covered with adhesive springs. The
      distribution of microvilli on the cell surface, the distribution of receptors on
      microvilli tips, and the forward and reverse reaction between receptor and ligand
      are all simulated using random number sampling of appropriate probability
      functions. The velocity of the cell at each time step in the simulation results
      from a balance of hydrodynamic, colloidal and bonding forces; the bonding force
      is derived by summing the individual contributions of each receptor-ligand
      tether. The model can simulate the effect of many parameters on adhesion, such as
      the number of receptors on microvilli tips, the density of ligand, the rates of
      reaction between receptor and ligand, the stiffness of the resulting receptor
      ligand springs, the response of springs to strain, and the magnitude of the bulk
      hydrodynamic stresses. The model can successfully recreate the entire range of
      expected and observed adhesive phenomena, from completely unencumbered motion, to
      rolling, to transient attachment, to firm adhesion. Also, the method can generate
      meaningful statistical measures of adhesion, including the mean and variance in
      velocity, rate constants for cell attachment and detachment, and the frequency of
      adhesion. We find a critical modulating parameter of adhesion is the fractional
      spring slippage, which relates the strain of a bond to its rate of breakage; the
      higher the slippage, the faster the breakage for the same strain. Our analysis of
      neutrophil adhesive behavior on selectin-coated (CD62-coated) surfaces in viscous
      shear flow reported by Lawrence and Springer (Lawrence, M.B., and T.A. Springer
      1991. Cell. 65:859-874) shows the fractional spring slippage of the CD62-LECAM-1
      bond is likely below 0.01. We conclude the unique ability of this selectin bond
      to cause neutrophil rolling under flow is a result of its unique response to
      strain. Furthermore, our model can successfully recreate data on neutrophil
      rolling as function of CD62 surface density.

PMID- 1384735
TI  - A semi-empirical approach for the simulation of circular dichroism spectra of
      gramicidin A in a model membrane.
AB  - In an extension of our previous work (Bano, M. C., Braco, L., and Abad, C. 1991.
      Biochemistry. 30:886-94), the kinetics of dissociation of gramicidin A double
      stranded dimers into beta 6.3-helical monomers in small unilamellar vesicles
      prepared following different protocols, were investigated using in combination
      circular dichroism (CD) and high-performance liquid chromatography (HPLC). The
      analysis of the data from both techniques according to a two-component model
      strongly supports that any given CD pattern of gramicidin incorporated in the
      phospholipid bilayer can be deconvoluted essentially as a linear combination of
      the reference subspectra calculated for the double-stranded dimer and the helical
      monomer. An HPLC-based, semi-empirical approach is proposed for the simulation of
      gramicidin CD curves in the model membrane used, and it is shown that the
      congruence between theoretical and experimental spectra is very satisfactory.

PMID- 1384737
TI  - Classification of projection images of crystalline arrays of the mitochondrial,
      voltage-dependent anion-selective channel embedded in aurothioglucose.
AB  - Low-dose electron microscopic images have been recorded from membrane crystals of
      the mitochondrial, voltage-dependent anion-selective channel, embedded in
      aurothioglucose. There is considerable variation in the high-resolution detail
      present in correlation averages computed from these images. Correspondence
      analysis reveals three classes of "control" averages, with main components of
      variation involving projected size of the pores and density modulations around
      the pores and in the corners of the unit cells away from the pores. Pretreatments
      that affect the functional state of the channel also affect the array averages.
      In particular, there appears to be a general correlation between the expected
      effector-induced state (i.e., open and closed) and the projected diameter of the
      channel lumens in the crystalline arrays.

PMID- 1384736
TI  - Properties of the mitochondrial peptide-sensitive cationic channel studied in
      planar bilayers and patches of giant liposomes.
AB  - A voltage-dependent cationic channel of large conductance is observed in
      phospholipid bilayers formed by the tip-dip method from proteoliposomes derived
      from mitochondrial membranes. It is blocked by peptide M, a 13 residue peptide
      having the properties of a mitochondrial signal sequence. To verify the
      reliability of the experimental approach, mitochondrial membranes from bovine
      adrenal cortex or porin-deficient mutant yeast were either fused to planar
      bilayers or incorporated in giant liposomes which were studied by patch clamp.
      Cationic channels were found with both techniques. They had the same conductance
      levels and voltage-dependence as those which have been described using the tip
      dip method. Moreover, they were similarly blocked by peptide M. The voltage
      dependence of block duration was analyzed in planar bilayer and tip-dip records.
      Results strengthen the idea that peptide M might cross the channel. Other
      mitochondrial channels were observed in planar bilayers and patch clamp of giant
      liposomes. Because they were never detected in tip-dip records, they are likely
      to be inactivated at the surface monolayer used to form the bilayer in this type
      of experiment.

PMID- 1384738
TI  - Conformational model for ion permeation in membrane channels: a comparison with
      multi-ion models and applications to calcium channel permeability.
AB  - The permeation properties of ion channels existing in several conductive states
      were analyzed. Each state was represented by the one-ion model. A special
      emphasis was placed on features, assumed to be indicative of a multi-ion mode of
      channel occupancy such as a deviation of concentration dependence of channel
      conductance from the Michaelis-Menten equation, an anomalous mole fraction
      effect, a strong voltage dependence of ion block and coupling of unidirectional
      fluxes (anomalous Ussing flux ratio). The conformational model was shown to have
      all these properties. The ion permeation through voltage-sensitive calcium
      channels fulfilled all the characteristics of the model proposed.

PMID- 1384739
TI  - 23Na and 1H NMR studies on melittin channels activated by tricyclic
      tranquilizers.
AB  - A dynamic 23Na nuclear magnetic resonance (NMR) technique was applied to the
      exchange system of Na+ ions present inside and outside large unilamellar vesicles
      at an equivalent concentration. Addition of melittin to phosphatidylcholine
      vesicles did not induce any detectable Na+ transport across the membrane but
      subsequent addition of a trace of chlorpromazine or imipramine did induce Na+
      transport. Because the formation of a drug-melittin adduct in a solution was
      detected by 1H NMR, the activation of melittin channels was assumed to originate
      from the direct interaction of the drug and melittin.

PMID- 1384740
TI  - Mode of action of iberiotoxin, a potent blocker of the large conductance Ca(2+)
      activated K+ channel.
AB  - Iberiotoxin, a toxin purified from the scorpion Buthus tamulus is a 37 amino acid
      peptide having 68% homology with charybdotoxin. Charybdotoxin blocks large
      conductance Ca(2+)-activated K+ channels at nanomolar concentrations from the
      external side only (Miller, C., E. Moczydlowski, R. Latorre, and M. Phillips.
      1985. Nature (Lond.). 313:316-318). Like charybdotoxin, iberiotoxin is only able
      to block the skeletal muscle membrane Ca(2+)-activated K+ channel incorporated
      into neutral-planar bilayers when applied to the external side. In the presence
      of iberiotoxin, channel activity is interrupted by quiescent periods that can
      last for several minutes. From single-channel records it was possible to
      determine that iberiotoxin binds to Ca(2+)-activate K+ channel in a bimolecular
      reaction. When the solution bathing the membrane are 300 mM K+ internal and 300
      mM Na+ external the toxin second order association rate constant is 3.3 x 10(6) s
      1 M-1 and the first order dissociation rate constant is 3.8 x 10(-3) s-1,
      yielding an apparent equilibrium dissociation constant of 1.16 nM. This constant
      is 10-fold lower than that of charybdotoxin, and the values for the rate
      constants showed above indicate that this is mainly due to the very low
      dissociation rate constant; mean blocked time approximately 5 min. The fact that
      tetraethylammonium competitively inhibits the iberiotoxin binding to the channel
      is a strong suggestion that this toxin binds to the channel external vestibule.
      Increasing the external K+ concentration makes the association rate constant to
      decrease with no effect on the dissociation reaction indicating that the surface
      charges located in the external channel vestibule play an important role in
      modulating toxin binding.

PMID- 1384741
TI  - The nucleic acid database. A comprehensive relational database of three
      dimensional structures of nucleic acids.

PMID- 1384742
TI  - Prolines are not essential residues in the "barrel-stave" model for ion channels
      induced by alamethicin analogues.
AB  - In the "barrel-stave" model for voltage-gated alamethicin channels in planar
      lipid bilayers, proline residues, especially Pro14, are assumed to play a
      significant role. Taking advantage of a previous synthetic alamethicin analogue
      in which all eight alpha-aminoisobutyric acids were replaced by leucines, two new
      analogues were prepared in order to test the effects of Pro14 and Pro2
      substitutions by alanines. The alpha-helical content of the three analogues in
      methanol solution remains predominant (between 63 and 80%). Macroscopic
      conductance experiments show that a high voltage dependence is conserved,
      although the apparent mean number of monomers forming the channels is
      significantly reduced when the substitution occurs at position 14. This is
      confirmed in single-channel experiments which further reveal faster fluctuations
      for the modified analogues. These results demonstrate that, although prolines,
      especially Pro14, are favorable residues for alamethicin-like events, they are
      not absolute prerequisites for the development of highly voltage-dependent
      multistate conductances.

PMID- 1384743
TI  - Ion channels in icosahedral virus: a comparative analysis of the structures and
      binding sites at their fivefold axes.
AB  - An analysis of the crystallographically determined structures of the icosahedral
      protein coats of Tomato Bushy Stunt Virus, Southern Bean Mosaic Virus, Satellite
      Tobacco Necrosis Virus, Human Rhinovirus 14 and Mengovirus around their fivefold
      axes is presented. Accessibilities surfaces, electrostatic energy profile
      calculations, ion-protein interaction energy calculations, free energy
      perturbation methods and comparisons with structures of chelating agents are used
      in this study. It is concluded that the structures built around the viral
      fivefold axes would be adequate for ion binding and transport. Relative ion
      preferences are derived for the binding sites, using free energy perturbation
      methods, which are consistent with the experimental data when available. In the
      cases where crystallographic studies determined the existence of ions on the
      fivefold axes, our results indicate that they would correspond to ions in
      crystallization or purification buffers. The environment of the fivefold axes are
      rich in polar residues in all icosahedral viral structures whose atomic
      coordinates are available, including some that are not being analyzed in detail
      in this work. The fivefold channel-like structures have most of the basic
      properties expected for real ion channels including a funnel at the entrance, a
      polar internal environment with frequent alternation of acidic and basic
      residues, ion binding sites, the capability to induce ion dehydration and ion
      transit from the external viral surface to the binding sites.

PMID- 1384744
TI  - Hydration at the membrane protein-lipid interface.
AB  - Evidence has been found for the existence water at the protein-lipid hydrophobic
      interface of the membrane proteins, gramicidin and apocytochrome C, using two
      related fluorescence spectroscopic approaches. The first approach exploited the
      fact that the presence of water in the excited state solvent cage of a
      fluorophore increases the rate of decay. For 1,6-diphenyl-1,3,5-hexatriene (DPH)
      and 1-palmitoyl-2-[[2-[4-(6-phenyl-trans-1,3,5-
      hexatrienyl)phenyl]ethyl]carbonyl]-3-sn-PC (DPH-PC), where the fluorophores are
      located in the hydrophobic core of the lipid bilayer, the introduction of
      gramicidin reduced the fluorescence lifetime, indicative of an increased presence
      of water in the bilayer. Since a high protein:lipid ratio was used, the
      fluorophores were forced to be adjacent to the protein hydrophobic surface, hence
      the presence of water in this region could be inferred. Cholesterol is known to
      reduce the water content of lipid bilayers and this effect was maintained at the
      protein-lipid interface with both gramicidin and apocytochrome C, again
      suggesting hydration in this region. The second approach was to use the
      fluorescence enhancement induced by exchanging deuterium oxide (D2O) for H2O.
      Both the fluorescence intensities of trimethylammonium-DPH, located in the lipid
      head group region, and of the gramicidin intrinsic tryptophans were greater in a
      D2O buffer compared with H2O, showing that the fluorophores were exposed to water
      in the bilayer at the protein-lipid interface. In the presence of cholesterol the
      fluorescence intensity ratio of D2O to H2O decreased, indicating a removal of
      water by the cholesterol, in keeping with the lifetime data. Altered hydration at
      the protein-lipid interface could affect conformation, thereby offering a new
      route by which membrane protein functioning may be modified.

PMID- 1384745
TI  - Limitations of the dual voltage clamp method in assaying conductance and kinetics
      of gap junction channels.
AB  - The electrical properties of gap junctions in cell pairs are usually studied by
      means of the dual voltage clamp method. The voltage across the junctional
      channels, however, cannot be controlled adequately due to an artificial
      resistance and a natural resistance, both connected in series with the gap
      junction. The access resistances to the cell interior of the recording pipettes
      make up the artificial resistance. The natural resistance consists of the
      cytoplasmic access resistances to the tightly packed gap junction channels in
      both cells. A mathematical model was constructed to calculate the actual voltage
      across each gap junction channel. The stochastic open-close kinetics of the
      individual channels were incorporated into this model. It is concluded that even
      in the ideal case of complete compensation of pipette series resistance, the
      number of channels comprised in the gap junction may be largely underestimated.
      Furthermore, normalized steady-state junctional conductance may be largely
      overestimated, so that transjunctional voltage dependence is easily masked. The
      model is used to discuss conclusions drawn from dual voltage clamp experiments
      and offers alternative explanations for various experimental observations.

PMID- 1384746
TI  - The impact of single cell voltage clamp on the understanding of the cardiac
      ventricular action potential.
AB  - In this article we review results obtained during the last decade by the single
      cell voltage clamp technique on cardiac ventricular myocytes, and we re-evaluate
      the major ionic currents underlying the cardiac action potential. Since its
      introduction into cardiac electrophysiology in the late seventies this technique
      has greatly contributed to our knowledge about the role of the transmembrane
      ionic currents in the heart. Recent findings gained with this method have
      confirmed that the inward sodium current is responsible not only for the fast
      depolarization, but, in part, also for the maintenance of the plateau phase of
      the action potential. The kinetics of the inward calcium current measured by the
      single cell voltage clamp technique proved to be much faster than was previously
      thought. In addition, two types of the inward calcium current with different
      physiological roles have recently been identified. The L-type calcium current
      plays an important part in maintaining the plateau phase of the action potential
      and may cause depolarization at less negative potentials. Although the
      physiological significance of the T-type calcium current is less clear, it
      appears to be involved in the pacemaker function of cardiac tissues. Single cell
      voltage clamp experiments have shown that the inward rectifier potassium current
      is not independent of time, as described earlier, but it helps to terminate the
      final phase of repolarization, and presumably controls the resting membrane
      potential. Recent studies with the single cell voltage clamp method have revealed
      that the delayed rectifier potassium current has, most probably, more than one
      component and is extensively modulated by neurotransmitters. Its main role is to
      initiate and terminate cardiac repolarization. This current is of particular
      importance in regulating rate-dependent repolarizations. The transient outward
      current, which rapidly activates and inactivates after depolarization, initiates
      early fast repolarization and may also take part in rate-dependent
      repolarization. The ionic carriers of this current are most likely potassium and
      chloride. The use of the single cell voltage clamp technique has led to the
      discovery of formerly unrecognized currents, like the ATP-dependent potassium
      current, the sodium activated potassium current and the chloride currents. The
      application of the new technique has made it possible to focus more attention on
      currents which were difficult to study previously, such as Na/K pump and Na/Ca
      exchanger currents.

PMID- 1384747
TI  - Perivascular innervation is lost in experimental atherosclerosis.
AB  - Nerve fibers, immunohistochemically positive for neuropeptide Y, tyrosine
      hydroxylase, calcitonin gene-related peptide and substance P, form a perivascular
      network surrounding the carotid arteries of New Zealand White rabbits.
      Transmission electron microscopy demonstrates that the nerve fibers are primarily
      located at the adventitial-medial border. Placing a silastic collar around a
      carotid artery for 14 days, in rabbits fed a diet high in cholesterol, resulted
      in a focal, intimal thickening in 10 out of 12 rabbits. Contralateral sham
      operated arteries showed no intimal thickening. At sites where intimal thickening
      occurred, there was a disappearance of the perivascular nerve network. The
      carotid arteries from rabbits that did not respond to the collar and the sham
      operated carotid arteries showed an intact and normal perivascular nerve network.
      In the group of animals which responded to the collar with intimal thickening,
      there was evidence of a proliferative response proximal to the collar and in this
      same tissue there was evidence of degeneration of nerve fibers. In conclusion, it
      has been demonstrated for the first time that, in regions of the carotid artery
      where intimal thickening occurred, there was an associated degeneration of the
      perivascular nerve network. The cause of this degeneration and its functional
      consequences require further investigation.

PMID- 1384749
TI  - Salt bridge induced changes in the secondary structure of ionic polypeptides.
AB  - The carboxylate-containing homopolypeptides poly(L-glutamate) [poly(Glu)] and
      poly(L-aspartate) [poly(Asp)] were found to form different types of ordered
      structures in the presence of poly(L-lysine) [poly(Lys)]. Mixing poly(Glu) with
      poly(Lys) in aqueous solution at neutral pH results in the instantaneous
      formation of a gel-like precipitate. The secondary structure of the gel
      precipitate can be best described as intermolecular antiparallel beta-strands,
      involving the backbone amide groups, as evidenced by the presence of
      characteristic amide I bands in the ir spectrum at 1684 and 1612 cm-1. Mixing
      poly(Asp) with poly(Lys) under identical conditions results in the formation of a
      fine precipitate with a different morphology. Examination of the ir spectrum of
      the precipitate revealed that unlike poly(Glu), poly(Asp) did not yield any
      discrete secondary structure upon precipitation with poly(Lys). Addition of
      solutions containing Ca2+ or Mg2+ to the poly(Glu)/poly(Lys) aggregates resulted
      in complete dissolution of the gel, with the disappearance of the ir bands
      characteristic of the intermolecular hydrogen-bonded network. The results
      demonstrate the importance of salt bridges in establishing strong hydrogen bonds
      between the backbone amide groups. Reaggregation occurred upon heating the
      poly(Glu)/poly(Lys) mixture in the presence of Ca2+, but not in the presence of
      Mg2+ ions. In the presence of Ca2+ ions, aggregation and formation of an extended
      hydrogen-bonded network occurred upon heating. The aggregates formed upon heating
      poly(Glu)/poly(Lys) in the presence of Ca2+ were attributed solely to
      complexation of Ca2+ to the carboxylate groups of poly(Glu) with poly(Lys)
      remaining free in solution. Dissolution of the aggregate could be accomplished
      through addition of Mg2+ at room temperature.

PMID- 1384748
TI  - Dipeptide backbone conformation and antibody recognition of a viral octapeptide
      epitope.
AB  - The peptide YKGTMDSG (Tyr-Lys-Gly-Thr-Met-Asp-Ser-Gly) represents an important
      antigenic determinant from the glycoprotein G2 of the pathogenic Rift Valley
      fever virus. By preparing a series of single-residue substitution peptides, the
      importance to antigenicity of individual residues within this octapeptide has
      been determined. Here, we investigated a simple and rapid computational analysis
      to test for correlations between the observed antigenicity of the substitution
      analogue peptides and the calculated conformational preferences in local regions
      of the peptides. Conformational energy analyses were carried out on all dipeptide
      combinations represented in the wild-type octapeptide and in the single-residue
      substitution analogue peptides. Conformational similarities and differences
      between wild-type and substitution dipeptide pairs were determined. The results
      of these computational analyses were then compared with the data on the relative
      antigenicity of the wild-type octapeptide and the substitution analogues. This
      comparison revealed a positive correlation. Substitution peptides showing changes
      in antigenicity possessed significant changes in the calculated backbone
      conformation relative to wild type in the dipeptides encompassing the residue
      substitution. Substitution peptides showing no change in antigenicity similarly
      showed no significant changes in dipeptide conformation. The potential utility of
      dipeptide conformational energy analyses and this preliminary structure-activity
      correlation are discussed.

PMID- 1384750
TI  - Structural investigation of helices II, III, and IV of B. megaterium 5S ribosomal
      RNA by molecular dynamics calculations.
AB  - The structures of the helices II-III region and the helix IV region of B.
      megaterium 5S rRNA have been examined by means of energy minimization and
      molecular dynamics calculations. Calculated distances between neighboring
      hydrogen-bonded imino protons in helices II, III, and IV were between 3.5 and 4.5
      A. The overall axis for the helices II-III region is warped rather than straight.
      Formation of additional Watson-Crick base pairs in loop B and loop C was not
      evident from the atomic positions calculated by molecular dynamics. Bases in loop
      C are well stacked, showing no significant change during dynamics. Bulge
      migration in helix III does not seem to be possible; the helices II-III region
      prefers one conformation. Helix II is more stable than helix III. Five base pairs
      in helix IV were sufficiently stable to establish that helix IV is terminated by
      a hairpin loop of three nucleotides. U87 protrudes from loop D. Structures of the
      helices II-III segment and the helix IV segment of B. megaterium 5S rRNA obtained
      by molecular dynamics were generally consistent with the solution structure
      inferred from high-field proton nmr spectroscopy.

PMID- 1384751
TI  - Hepatotoxicity induced by a single ip injection of ruthenium red.
AB  - Ruthenium red (RR) has been used as a marker in morphological observations of the
      glycocalix because it interacts with polyanionic mucopolysaccharides. This fact
      may explain its agglutinating effect on rat blood red cells following a single 20
      mg/kg intraperitoneal injection, which increases with time post-injection. This
      study was performed to determine whether such an effect was due to a direct
      effect of the RR on the blood cells, to interference with coagulation, or to the
      non-specific general toxicity of this dye. Male rats were injected with 20 mg/kg
      RR ip and the enzymatic and coagulation parameters, plus the liver morphology
      were examined. Alanine aminotransferase (ALAT) activity was increased at 30, 60
      and 120 min, and aspartic aminotransferase (ASAT) activity was increased 60, 120
      and 480 min after RR injection. The prothrombin time (PT) and partially activated
      thromboplastin time (PTT) were significantly decreased, particularly after 60-120
      min. The liver had an external granular appearance with clear signs of congestion
      and oedema, and showed degenerative changes very soon after RR injection. A
      single administration of RR induces serious functional and structural changes in
      the liver. Such a toxicity, and these changes must be taken into consideration,
      particularly with regard to neurological studies.

PMID- 1384752
TI  - T-lymphocyte control of HLA-DR blood monocyte differentiation into neo
      fibroblasts. Further evidence of pluripotential secreting functions of HLA-DR
      monocytes, involving not only collagen but also uromodulin, amyloid-beta peptide,
      alpha-fetoprotein and carcinoembryonic antigen.
AB  - Previous studies led us to demonstrate in pathological situations that the
      fibroblast, not the macrophage, was the terminal maturation step of the HLA-DR
      monocyte and that the entire process came under T-lymphocyte control. Fibrosis
      which developed under immunosuppressive treatment (cyclosporin) after organ
      transplantation is an illustration of these in vitro observations. The present in
      vitro study was undertaken in order to investigate whether or not this
      transformation process takes place under physiological conditions and if so, the
      nature of the T-lymphocyte control. We report that normal HLA-DR
      monocytes/macrophages are able to secrete type 1 collagen and to differentiate
      into neo-fibroblasts. However, contrarily to what happened in pathology, only a
      few neo-fibroblasts developed transiently. The addition of conditioned medium
      (CM) from activated T-lymphocytes greatly enhanced the transformation process.
      Counteracting this CM effect, cell-to-cell contact between neo-fibroblasts and T
      cells resulted in the loss of fibroblastic shape. The 'end-result' macrophage
      engulfed numerous lymphocytes giving rise to a multinucleated cell. This giant
      cell no longer adhered to the slide and died. The question is raised as to
      whether the process observed in vitro is involved in vivo in tissue repair. We
      also report that HLA-DR monocytes and the neo-fibroblasts which derive from them
      are able to secrete, in addition to type 1 collagen, a variety of proteins such
      as uromodulin, amyloid-beta peptide, alpha-fetoprotein and carcinoembryonic
      antigen. In cystic fibrosis we previously reported a high level of uromodulin
      production by HLA-DR monocytes differentiating towards the fibroblastic
      phenotype. Pathologies characterized by excessive production of either alpha-feto
      protein, carcinoembryonic antigen, beta-amyloid protein (Alzheimer's disease)
      should be investigated, taking into account the involvement of HLA-DR monocytes
      and their possible uncontrolled differentiation into neo-fibroblasts.

PMID- 1384753
TI  - ConA induced changes in energy metabolism of rat thymocytes.
AB  - The influence of ConA on the energy metabolism of quiescent rat thymocytes was
      investigated by measuring the effects of inhibitors of protein synthesis,
      proteolysis, RNA/DNA synthesis, Na+K(+)-ATPase, Ca(2+)-ATPase and mitochondrial
      ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of
      quiescent thymocytes could be assigned to specific processes using two different
      media. Under these conditions the oxygen is mainly used to drive mitochondrial
      proton leak and to provide ATP for protein synthesis and cation transport,
      whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent
      proteolysis was not measurable. The mitogen ConA produced a persistent increase
      in oxygen consumption by about 30% within seconds. After stimulation more than
      80% of respiration could be assigned to specific processes. The major oxygen
      consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak,
      protein synthesis and Na+K(+)-ATPase with about 20% each of total oxygen
      consumption, while Ca(2+)-ATPase and RNA/DNA synthesis contribute about 10% each.
      Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen
      consumption remains unexplained. In contrast, the pattern of energy metabolism in
      stimulated thymocytes is similar to that described for Ehrlich Ascites tumour
      cells and splenocytes, which may also be in an activated state. Most of the
      oxygen consumption is accounted for, so the unexplained process(es) in
      unstimulated cells shut(s) off on stimulation.

PMID- 1384754
TI  - Rat bone marrow erythroid cell fractionation by counter current distribution in
      non-charge-sensitive two-phase systems.
AB  - Counter-current distribution in non charge-sensitive aqueous poly(ethylene
      glycol)-dextran two phase systems allows the fractionation of rat bone marrow
      cells into two broad cell subpopulations with different distribution coefficients
      in a relatively short time. Morphological identification and enzymatic studies
      suggest that erythroid cells are mainly present in the subpopulation with the
      higher distribution coefficient. The distribution coefficient and, therefore,
      surface hydrophobicity of these cells, apparently increase in parallel with an
      increase in their degree of differentiation and maturation.

PMID- 1384755
TI  - Elementary steps in synaptic transmission revealed by currents through single ion
      channels.

PMID- 1384756
TI  - Lindane-induced modifications to membrane lipid structure: effect on membrane
      fluidity after subchronic treatment.
AB  - Chronic lindane intoxication by injecting subcutaneously the toxicant, resulted
      in an altered lipid pattern in rat ventral prostate membranes. An increase of
      membrane fluidity was also observed using a fluorescence polarization technique.
      When in vitro experiments were carried out with both treated and untreated rats,
      an interesting lack of parallelism was found, which could indicate the
      development of a resistance to membrane disordering by lindane. The observed
      changes in cholesterol and phospholipid composition are also consistent with the
      hypothesis that lindane perturbs the lipid matrix of membranes, possibly inducing
      complex compensatory changes in the membrane lipid composition.

PMID- 1384757
TI  - Neural correlates of memory storage. The role of ion channels.

PMID- 1384758
TI  - Functional regulation of nicotinic acetylcholine receptor channels in muscle.

PMID- 1384759
TI  - Rapid activation and desensitization of transmitter-liganded receptor channels by
      pulses of agonists.

PMID- 1384760
TI  - Kinetic properties and regulation of GABAA receptor channels.
AB  - Single-channel recordings of GABAA receptor single-channel currents have been
      obtained from mouse spinal cord neurons in cell culture. Detailed kinetic
      analysis of single-channel main-conductance level currents has allowed
      development of a preliminary kinetic scheme which describes the gating of the
      GABAA receptor channel. The essential features of this kinetic scheme are
      presented in scheme 1 (see above). In this scheme, the GABAA receptor channel is
      envisioned to exist in multiple open and closed states. Properties can be broken
      into three main categories. First, the receptor can exist in a closed and
      nondesensitized set of states. In the kinetic model it is envisioned that there
      is an unbound (C13), a singly bound (C12), and two doubly bound (C11 and C10)
      closed states. The singly bound and doubly bound closed states are thought to
      open to three open states (O1, O2, O3). However, each of the open states opens to
      two distal closed states whose kinetic properties are similar for all three open
      states (C4-C9). Only one desensitized state (D0) has been incorporated into the
      model. While this characterization of desensitization is certainly incomplete, it
      is an initial step toward including the desensitization process which is clearly
      evident in whole-cell and single-channel recordings. This kinetic scheme should
      be considered only an initial working model. A number of features appear to be
      correct. First, all analyses of open time frequency histograms for GABA- and GABA
      agonist-induced single-channel openings have demonstrated the presence of at
      least three distinct open time constants. Furthermore, the concentration
      dependent change in the relative frequency of occurrence of the three open states
      suggests that the open states occur from singly and doubly bound forms of the
      receptor. Second, the presence of two brief closed states adjacent to the open
      states appears fairly secure. However, it should be noted that the kinetic
      analysis primarily suggests that each open state opens to two brief adjacent
      closed states in a concentration-independent manner. While we have indicated that
      these two closed states are distal to the three open states, the actual
      assignment of the location of these states is unclear. Another interpretation of
      these data is that there is only a single distal closed state and that the
      proximal, extraburst closed states have very brief durations that are similar to
      each other. What appears clear, however, is that the open states can close to
      either brief closed state.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1384761
TI  - Intracellular regulation of GABAA-receptor function.

PMID- 1384762
TI  - Prebypass glucose-insulin-potassium infusion in elective nondiabetic coronary
      artery surgery patients.
AB  - Perioperative GIK therapy has been advocated to ensure adequate energy substrate
      levels during cardiac surgery. However, hyperglycemia should be avoided because
      it may worsen neurologic outcome after cerebral ischemia. A prospective,
      randomized, clinical comparison was performed between two prebypass infusion
      regimens in 32 elective nondiabetic CABG patients. Sixteen patients (GIK group)
      received glucose, 0.6 g/kg/h, insulin, 0.12 U/kg/h, and KCl, 0.12 mmol/kg/h, from
      the induction of anesthesia to the start of CPB; while the remaining 16 patients
      (R group) received only Ringer's acetate. The pump prime was glucose free and a
      blood cardioplegia technique was used in both groups. No differences were found
      between the groups with regard to myocardial injury; the CK-MB enzyme fractions
      were elevated to a similar degree and the frequency of postoperative ECG changes
      were similar in both groups. Likewise, there were no differences in hemodynamic
      changes, need for inotropic support, arrhythmia frequency, or duration of ICU
      stay. The GIK patients had higher blood glucose (P < 0.05) and insulin levels (P
      < 0.01); blood glucose increased to 12.4 +/- 5.4 mmol/L (mean +/- SD) at
      cannulation, with a drop after starting bypass. Interindividual variation in GIK
      patients was great, with glucose values ranging between 20.1 mmol/L at
      cannulation to 2.0 mmol/L after starting CPB. A hyperglycemic response was seen
      in both groups during rewarming: 15.0 +/- 4.2 and 15.0 +/- 3.1 mmol/L in GIK and
      R patients, respectively. It is concluded that prebypass GIK infusion had no
      clinical benefits for elective CABG patients as compared to Ringer's
      acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384763
TI  - Neuroanatomical labeling with biocytin: a review.
AB  - Recent studies have shown that biocytin may have multiple applications in
      neuroanatomical studies. Biocytin may be injected into the brain by iontophoresis
      or by pressure injection methods, and localized in tissue sections using avidin
      conjugated labels. It is taken up by neurons and rapidly transported down axons
      in an anterograde fashion. Axons are completely labeled in a Golgi-like manner
      and can be examined at both light and electron microscopic levels. Biocytin can
      also be used in retrograde tract tracing experiments, although in some cases it
      appears that fibers must be damaged to produce such labeling. Retrogradely
      labeled cells may be completely labeled, resembling neurons stained with the
      Golgi technique. Individual neurons can also be labeled in a Golgi-like manner by
      uptake of biocytin from the extracellular space. Thus, it appears that biocytin
      is an especially versatile marker for neuroanatomical investigations.

PMID- 1384765
TI  - Noradrenergic excitatory inputs to median preoptic neurones in rats.
AB  - Extracellular single-unit activity was recorded from 21 median preoptic nucleus
      (MnPO) neurones, antidromically identified as projecting to the hypothalamic
      paraventricular nucleus (PVN), in urethane-anaesthetized male rats. Of these
      identified MnPO neurones, 14 displayed an excitatory response in neuronal
      excitability following electrical stimulation (5 Hz, 600 microA) of the A1
      noradrenergic region of the ventrolateral medulla, while the remaining neurones
      were unresponsive. The excitatory response of MnPO neurones was blocked by
      microiontophoretically applied phentolamine, an alpha-adrenoceptor antagonist,
      but not by timolol, a beta-adrenoceptor antagonist. These results suggest that
      the A1 region acts to enhance the activity of MnPO neurones projecting to the PVN
      via an alpha-adrenoceptor mechanism.

PMID- 1384764
TI  - Colocalization of nitric oxide synthase and NADPH-diaphorase in rat adrenal
      gland.
AB  - The distribution and colocalization of nitric oxide synthase (NOS) and reduced
      nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase was studied in the
      neuronal elements of the adrenal gland of the rat. Ganglion cells and many nerve
      fibres in the gland showed both NOS-immunoreactivity and NADPH-diaphorase
      staining. The adrenal cortical cells showed NADPH-diaphorase staining but were
      not immunoreactive for NOS. Positive labelling for both NADPH-diaphorase and NOS
      was found in bundles and in single fibres with varicosities, preferentially
      located around the noradrenaline (NA)-storing cells. Adrenaline (A)-storing cells
      and ganglion cells in the medulla, along with the cortical cells and blood
      vessels in the zona glomerulosa, received relatively fewer positive fibres.

PMID- 1384766
TI  - P0 protein in normal, trembler heterozygous/homozygous mice during active PNS
      myelination.
AB  - The quantification of P0 protein has been currently used to measure the
      myelination of the peripheral nervous system (PNS). Using immunological
      techniques, we show that, as early as postnatal day 8, the P0 content of mice
      homozygous and heterozygous for the Trembler mutation, represent respectively one
      tenth and half of the normal values. Thus, although the Trembler mutation is
      dominant, the myelination defect observed in heterozygous Trembler mice is more
      pronounced in the homozygous Trembler mice. This gene dosage effect should be
      taken into account when a molecular model of the Trembler mutation will be
      proposed.

PMID- 1384768
TI  - Inhibition of nitric oxide synthase protects against hypoxic neuronal injury.
AB  - We investigated the action of nitric oxide in hypoxic neuronal injury, using the
      hippocampal slice. Inhibition of nitric oxide synthase with the competitive
      inhibitor, NG-monomethyl-L-arginine, provided significant protection against
      hypoxia for population spike, EPSP and fiber volley responses, with an EC50 of 30
      microM for protection of antidromic population spike amplitude. Confirming a
      stereo-specific site of action, this protection was reversed by the addition of L
      arginine, but not D-arginine. These results indicate that nitric oxide generation
      may mediate acute CA1 neuronal injury during hypoxia, and that inhibition of
      nitric oxide synthase may be a useful neuroprotective strategy.

PMID- 1384767
TI  - Decrease in rat brain calcitonin binding sites and adenylyl-cyclase activity
      during ageing.
AB  - In order to investigate the effects of ageing on the cerebral receptors for
      calcitonin (CT), we used an in vitro autoradiographic method to study the
      distribution of the binding sites for eel CT (eCT) in young and old rat brain.
      The inhibitory action of eCT on adenylyl-cyclase (AC) activity upon isolated
      brain cell membranes was also evaluated. The results show area-specific reduction
      of binding particularly in the hypothalamus and pons medulla of the old rat. The
      inhibitory action of eCT on AC activity was significantly reduced in the same
      areas, whereas in the striatum and mesencephalon no changes were observed. The
      parallel decrease of binding of eCT and of the inhibitory action of eCT on AC in
      ageing may represent a functional decline of neuronal activities during ageing.

PMID- 1384769
TI  - Nitric oxide synthase in VIP-containing vasodilator nerve fibres in the guinea
      pig.
AB  - We investigated the possibility of nitric oxide (NO), a powerful vasodilator
      agent, being synthesized by perivascular nerve fibres. Immunoreactivity and
      catalytic activity of the NO synthesizing enzyme, NO synthase (NOS), were
      demonstrated in perivascular nerve fibres of blood vessels receiving autonomic
      vasodilator innervation, but not of those innervated exclusively by
      vasoconstrictor nerve fibres. Double-labelling techniques allowed identification
      of NOS-containing nerve fibres as belonging to the vasoactive intestinal peptide
      (VIP)/acetylcholine-containing class whereas noradrenergic and substance P
      containing perivascular fibres were devoid of NOS. We suggest that, in addition
      to its endothelial source, NO is a neuronal co-mediator of VIP/cholinergic
      vasodilation.

PMID- 1384770
TI  - The AMPA antagonist, NBQX, protects against ischemia-induced loss of cerebellar
      Purkinje cells.
AB  - We examined the effect of an AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole)
      antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline (NBQX), on
      rat cerebellar Purkinje cell loss and hippocampal pyramidal CA1 cell loss, after
      10 minutes of global cerebral ischemia. NBQX was given intraperitoneally in a
      dose of 30 mg kg-1 at the end of ischemia, and 10 and 25 minutes later. Rats
      subjected to ischemia without post-ischemic administration of NBQX served as
      controls. Four days after ischemia the cerebellar Purkinje cell density was
      higher and the density of acidophilic (dead) Purkinje cells lower in the NBQX
      treated animals compared with the control animals (p = 0.01 and p less than 0.005
      respectively). There was partial to total loss of pyramidal neurons in the CA1
      region of the dorsal hippocampus in control animals, but no CA1 pyramidal neuron
      loss in the NBQX treated animals (p = 0.001).

PMID- 1384771
TI  - A nitric oxide (NO) synthase inhibitor accelerates amygdala kindling.
AB  - In response to NMDA receptor activation, hippocampal, striatal and cerebellar
      neurons synthesize nitric oxide (NO), which in turn elevates cGMP levels via
      guanylate cyclase. NO is increasingly being considered as a transsynaptic
      retrograde messenger, involved in neuronal plasticity. The effect of an inhibitor
      of NO synthase, L-NG-nitroarginine (NOArg), was studied on amygdala kindling and
      on kindled seizures in rats. NOArg increased kindling rate, particularly in its
      initial period, but did not modify seizure severity in previously kindled rats,
      although we have no definitive explanation for this effect. However, an enhanced
      post-synaptic excitability could be attributed to the blockade of the negative
      feed-back exerted by NO on the NMDA receptor.

PMID- 1384772
TI  - Transport of RNA between nucleus and cytoplasm.
AB  - The transport out of the nucleus of RNAs transcribed by RNA polymerase II (U
      snRNAs and mRNAs) has not been extensively studied. Basic questions, such as
      whether export requires association of the RNA with specific proteins, are not
      yet definitively answered. Nevertheless, recent progress in this area has been
      significant. Sequence or structural features of RNAs which are either required
      for export or which result in nuclear retention have been defined. These are
      presumed to interact with components of the transport machinery or with anchoring
      nuclear factors respectively. The unexplained dependence of the transport of
      certain mRNAs on either intervening sequences or for transcription from specific
      promoters suggests that RNAs may have to pass through different intranuclear
      compartments before export. Studies of the import of RNAs from the cytoplasm has
      revealed that different classes of nuclear localization signals exist, and
      protein components of viral RNPs that appear to determine the direction in which
      they move through the nuclear envelope have been identified.

PMID- 1384773
TI  - RNA nucleocytoplasmic transport.
AB  - The transport of RNAs from the nucleus to the cytoplasm is an obligatory step in
      gene expression and may also be a target for regulation. The cellular machinery
      has the capacity to export a myriad of RNA transcripts, which differ
      significantly in sequence and structure. Recent work is providing the first
      glimpses into how RNA export occurs.

PMID- 1384774
TI  - Differential effects of IL-3, GM-CSF and G-CSF in an adult with congenital
      neutropenia.
AB  - Using a methylcellulose culture system, we studied the effects of recombinant
      human interleukin-3 (IL-3), recombinant human granulocyte-macrophage colony
      stimulating factor (GM-CSF), and recombinant human granulocyte colony-stimulating
      factor (G-CSF) on the growth of myeloid progenitor cells (CFU-C) from an adult
      patient with congenital neutropenia. The moderate clinical course and the
      maturation arrest at blast-promyelocyte stage in the marrow differentiated this
      patient from those described as having Kostmann-type congenital neutropenia. CFU
      C growth in bone marrow cells from the patient responded to IL-3 normally in a
      dose-dependent manner. GM-CSF stimulated only macrophage colony formation in a
      dose-dependent manner comparable to that in normal subjects. Neither GM-CSF nor G
      CSF stimulated any significant granulocyte colony formation. This evidence
      suggests that the hematopoietic progenitor cells in this patient had the
      potential for developing CFU-C with IL-3, and that the neutropenia in this
      patient could be a result of an intrinsic defect in myelopoiesis along a
      granulocytic pathway responsive to GM-CSF or G-CSF.

PMID- 1384775
TI  - Trophic effect and modulation of ACTH-dependent stimulation of steroidogenesis by
      prolactin in guinea pig adrenal cortex.
AB  - The effect of PRL in intact guinea pig on the incorporation of specific labelled
      precursors into DNA, RNA, proteins and corticosteroids in adrenocortical tissue
      of intact guinea pig at different levels of activation of the gland were studied.
      PRL (2 IU/100 g daily) did not cause any significant changes until 3 days of
      treatment. PRL administered alone for 3 days caused significant elevation of 3H
      thymidine incorporation into DNA in adrenocortical slices and no significant
      changes in labelling of RNA, protein and corticosteroids. In contrast, PRL
      administered together with ACTH (0.5 IU/100 g) for 3 days did not affect DNA
      synthesis but caused increase of 3H-cholesterol incorporation into cortisol and
      cortisone additionally to the ACTH action. Labelling of 17-deoxycorticosteroids
      in adrenocortical slices from animals of ACTH+PRL group either did not change
      significantly (aldosterone) or decreased (corticosterone).

PMID- 1384776
TI  - [Effects of parathormone on 45Ca2+ accumulation in neurosecretory cells and
      contents of vasopressin in blood after administration of parathyroidin in
      parathyroid gland insufficiency].
AB  - The functional state of hypothalamic-hypophyseal-neurosecretory complex was
      studied in parathyroidin injection and hypofunction of the parathyroid glands. In
      these conditions vasopressin levels in blood of the rats increased. The
      incubation of the hypothalamus with parathormone and 45Ca2+, as well as the
      injection of parathyroidin increased 45Ca2+ transfer to the neurosecretory cells
      and vasopressin release in the blood. Various mechanisms of similar influence of
      the parathormone and hypofunction of the parathyroid glands on a vasopressin
      level in blood are discussed.

PMID- 1384777
TI  - [Effects of pesticide fluometuron (cotoran) on template synthesis of RNA].
AB  - The experiments on the investigation of pesticide fluometuron (cotoran) influence
      on nuclease sensitivity and template activity of rat liver chromatin were carried
      out. Cotoran was found to bind specifically with non-histone proteins of
      chromatin. It was shown that this pesticide considerably decreases template
      activity of chromatin and its sensitivity to the action of nucleases. It
      suggests, that certain conformation changes occur in chromatin upon the action of
      cotoran.

PMID- 1384778
TI  - [Effects of flavobion on nucleic acids in tissues of rats irradiated with gamma
      rays].
AB  - Flavobion /SPOFA/ is a hepatoprotective preparation containing an effective
      constituent--the flavonoids, namely, silybin, silydianin and silychristin,
      collectively referred to as silymarin. Silymarin can influence certain metabolic
      processes including RNA synthesis and stabilize cell membranes. Suspension of
      this preparation was given p. o. by tube in a dose of 70 mg/kg, one hour before
      whole-body irradiation with a 5.7 Gy dose of gamma radiation (60Co). Animals were
      subjected to partial hepatectomy/by 30 min. after irradiation/and examined on
      hour 30 after operation. The changes in concentration and total content of RNA
      and DNA in the liver (both intact and regenerating), spleen and bone marrow were
      followed. We found that Flavobion administration influenced the concentration and
      total content of RNA and DNA in the spleen and bone marrow. However, in a target
      organ, liver, changes in nucleic acids were less pronounced.

PMID- 1384779
TI  - [Effects of exogenous poly(A)+ mRNA on antigenic properties and growth of Krebs-2
      tumor cells].
AB  - The treatment of Krebs-2 ascitic tumor cells (TC) with total RNA from the liver
      of Wistar rats (2 mg/ml) altered their antigenicity. As a result, the growth of
      treated TC in contrast with untreated TC was inhibited when transplanted i. m. to
      mice preimmunized with rat liver homogenate. Investigations of poly(A+)mRNA, rRNA
      and tRNA isolated from the same tissue established that the alteration of
      antigenicity is due to mRNA (8-24 micrograms/ml). In the cytotoxicity assay with
      antisera against rat Wistar antigens, the expression of rat antigens in TC
      treated mRNA was observed in the next cell generations.

PMID- 1384780
TI  - [Hypotrypsinemia as a possible factor in the activation of motor function of the
      duodenum in pancreatic atrophy in rats].
AB  - The effect of pancreas atrophy on myoelectrical activity of the duodenum and
      serum trypsin, trypsin inhibitor, amylase, lipase activity has been described.
      The activation of the duodenum motor activity has been established. The changes
      in the motor activity were connected with trypsin and trypsin inhibitor activity
      of serum. The motor activity changes were compensated by trypsin therapy.

PMID- 1384781
TI  - [Light-optical and ultrastructural immunohistochemistry of antigen H-4, a common
      marker of epithelial cells].
AB  - Epitope localization reacting with mice monoclonal antibodies (Mabs) H 4 was
      investigated using the specimen of epithelium of skin, human uterine cervix as
      well as in the culture of epithelium cells of guinea-pig duct deferent. Mice
      monoclonal antibodies against antigen H 4 obtained by the hybridoma method after
      immunization of mice with rat colon epithelium cytoskeletal fractions were used.
      Mabs H 4 were shown to react with antigen of intermediate filaments of all
      studied normal epithelial, cancer cells as well as culture epithelial cells. Mabs
      H 4 are supposed to be used as a unique immunohistochemical marker of epithelium
      cells under normal and malignant growth conditions.

PMID- 1384782
TI  - [Identification, purification and physico-chemical properties of neurospecific
      alpha 1-globulin].
AB  - The partially purified and concentrated 500-600-folds protein fraction has been
      obtained from human brain extract. This protein fraction was used for the
      immunization of rabbits. The corresponding anti-sera have the potency to detect
      the brain specific alpha 1-globulin, which is not identical to known
      cytoplasmatic brain specific protein. These antisera were used for the control of
      the antigen purification procedure which included ion-exchange, affinity and
      hydropho'ic chromatography, gel-filtration and isochromatofocusing. The antigen,
      purified to the homogeneity, has the electrophoretic mobility of the alpha 1
      globulins, M(r) = 110-10 kD, and isoelectric point at pH 2.9-3.1.

PMID- 1384783
TI  - [Effects of concanavalin A on different variants of adhesive reactions of human
      neutrophils].
AB  - The influence of Con A on human neutrophils adhesion in interactions with
      sepharose 4B, C3b-sephadex G-25, DEAE-sephadex A-25, polymethylmethacrylate was
      studied. In concentrations 25 mg/ml and more Con A completely inhibited IgG
      dependent adhesion but had no influence on other types of adhesion reactions. The
      effect was due to Con A interaction with neutrophils and could not be reproduced
      by Con A pretreatment of IgG-sepharose. Results are considered to be a
      manifestation of lectin-dependent modulation of cell receptors functions.

PMID- 1384784
TI  - The protective effect of colchicine on bleomycin-induced pulmonary fibrosis in
      rats.
AB  - With the purpose of evaluating the therapeutic effect of colchicine on lung
      fibrosis in rats, bleomycin A5 (BLM-A5) was injected intratracheally to produce a
      lung fibrosis model. The animals were then treated with colchicine, 50
      micrograms/d i.m. One month later, collagen fiber deposition scores (stained by
      Masson trichrome) were significantly lower in the treated group than in the
      untreated group (P less than 0.01). This result was proved further by assaying
      total lung hydroxyproline content (P less than 0.05). Histopathologic findings
      showed that the proliferation of fibroblasts dropped slightly in the treated
      group as compared with the untreated group. From this study, we conclude that
      colchicine has certain antifibrotic effects and may be used in the treatment of
      pulmonary fibrosis.

PMID- 1384785
TI  - In vivo effect of interleukin-1 alpha on hematopoiesis: role of colony
      stimulating factor receptor modulation.
AB  - To determine the mechanism(s) by which interleukin-1 (IL-1) promotes
      granulopoiesis in vivo, we examined the effect of in vivo administration of IL-1
      alpha on colony-stimulating factor (CSF) receptor expression on bone marrow cells
      (BMCs) and whether this directly correlated with progenitor cell responsiveness.
      Administration of IL-1 alpha to mice induced the upregulation of both granulocyte
      macrophage-CSF (GM-CSF) and IL-3 receptors, which reached a maximum 24 hours
      after IL-1 alpha injection on unfractionated BMCs. This upregulation was more
      pronounced on the progenitor-enriched cell population (lineage-negative [Lin(
      )]). The enhanced GM-CSF and IL-3 receptor expression directly correlated with
      enhanced IL-3- or GM-CSF-induced growth of colony-forming unit-culture (CFU-c) or
      CFU-mixture (CFU-Mix; colonies containing macrophages, granulocytes, and
      erythroid cells). In addition, the absolute number of high proliferative
      potential-colony-forming cells (HPP-CFC) was increased fivefold. In contrast,
      granulocyte-CSF (G-CSF)-specific binding on unfractionated BMCs was rapidly (4
      hours) reduced after IL-1 alpha administration and returned to control levels by
      24 hours. This reduction correlated with IL-1 alpha-induced margination of mature
      granulocytes (RBC-8C5hi cells), which express high levels of G-CSF receptors. IL
      1 alpha treatment did not affect G-CSF receptor expression on Lin- cells.
      Pretreatment of mice with anti-type I IL-1 receptor antibody blocked the IL-1
      alpha-induced upregulation of GM-CSF and IL-3 receptor expression on BMCs. Taken
      together, as one possible mechanism, IL-1 alpha in vivo may stimulate the
      expression of functional GM-CSF and IL-3 receptors on BMCs indirectly, and, in
      concert with the induction of circulating CSF levels, may account for the ability
      of IL-1 alpha to stimulate hematopoiesis in vivo.

PMID- 1384786
TI  - Characterization of primitive hematopoietic cells in normal human peripheral
      blood.
AB  - The total number of clonogenic cells present in 5-week-old long-term cultures
      (LTC) initiated by seeding normal human marrow cells on competent adherent cell
      feeder layers allows for the quantitation of a more primitive hematopoietic input
      precursor cell type referred to as an LTC-initiating cell (LTC-IC). Previous
      studies have suggested that LTC-IC also circulate because production of
      clonogenic cells continues for many weeks when cells from the light-density (<
      1.077 g/mL), T-cell-depleted fraction of normal blood are maintained on
      irradiated, marrow-derived feeder layers in LTC medium. We now show that the
      number of clonogenic cells present in such reconstructed LTC after 5 weeks is
      linearly related to the input number of peripheral blood (PB) cells over a wide
      range of cell concentrations, thereby permitting the quantitation of circulating
      LTC-IC by limiting dilution analysis. Using this approach, we have found the
      concentration of LTC-IC in the circulation of normal adults to be 2.9 +/- 0.5/mL.
      This is approximately 75-fold lower than the concentration of circulating
      clonogenic cells (ie, burst-forming units-erythroid plus colony-forming units
      [CFU] granulocyte-macrophage plus CFU-granulocyte, erythroid, monocyte,
      megakaryocyte) and represents a frequency of LTC-IC relative to all nucleated
      cells that is approximately 100-fold lower than that measured in normal marrow
      aspirate samples. Characterization studies showed most circulating LTC-IC to be
      small (low forward light scatter and side scatter), CD34+, Rh-123dull, HLA-DR-,
      and 4-hydroperoxycyclophosphamide-resistant cells, with differentiative and
      proliferative potentialities indistinguishable from LTC-IC in normal marrow.
      Isolation of the light-density, T-cell-depleted, CD34+, and either HLA-DR(low) or
      Rh-123(dull) fraction of normal blood yielded a highly enriched population of
      cells that were 0.5% to 1% LTC-IC (approximately 1,500-fold enriched beyond the
      light-density, T-cell-depletion step), a purity comparable to the most enriched
      populations of human marrow LTC-IC reported to date. However, purification of PB
      LTC-IC on the basis of these properties did not allow them to be physically
      separated from a substantial proportion (> 30%) of the clonogenic cells in the
      same samples, in contrast to previous findings for LTC-IC and clonogenic cells in
      marrow. These studies show the presence in the blood of normal adults of a
      relatively small but readily detectable population of functionally defined,
      primitive hematopoietic cells that share properties with marrow LTC-IC, a cell
      type thought to have in vivo reconstituting potential.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1384787
TI  - Phenotypic heterogeneity of primitive leukemic hematopoietic cells in patients
      with chronic myeloid leukemia.
AB  - The peripheral blood of chronic myeloid leukemia (CML) patients with chronic
      phase disease and elevated white blood cell (WBC) counts typically contains
      markedly increased numbers of a variety of neoplastic pluripotent and lineage
      restricted hematopoietic progenitors. These include cells detected in standard
      colony assays as well as their more primitive precursors. The latter are referred
      to as long-term culture-initiating cells (LTC-IC) because of their ability to
      generate clonogenic cell progeny detectable after a minimum of 5 weeks incubation
      on competent fibroblast feeder layers. In this study, we have investigated a
      number of the properties of the LTC-IC and clonogenic cells present in the blood
      of such CML patients with high WBC counts. This included an analysis of the light
      scattering properties of these progenitors, as well as their expression of CD34
      and HLA-DR, Rhodamine-123 staining, and in vitro sensitivity to 4
      hydroperoxycyclophosphamide. In the case of LTC-IC, the production of different
      types of lineage-restricted and multipotent progeny was also analyzed. Most of
      the circulating LTC-IC and clonogenic cells in the CML patients studied (on
      average approximately 70% and approximately 90%, respectively) showed features of
      proliferating or activated cells. This is in marked contrast to the majority of
      progenitors in the blood of normal individuals and most of the LTC-IC in normal
      marrow, all of which exhibit a phenotype expected of quiescent cells.
      Interestingly, a significant proportion of the circulating clonogenic cells and
      LTC-IC in the CML samples studied (on average approximately 10% and approximately
      30%, respectively) appeared to be phenotypically similar to normal circulating
      progenitors, although their absolute numbers were indicative of a neoplastic
      origin. Both phenotypes of circulating CML clonogenic cells and LTC-IC could be
      obtained at approximately 10% to 20% purity by differential multiparameter
      sorting. These findings suggest that expansion of the Philadelphia chromosome
      positive clone at the level of the earliest types of hematopoietic cells results
      from the activation of mechanisms that enable some, but not all, signals that
      block the cycling of normal stem cells to be bypassed or overcome. In addition,
      they provide strategies for purifying these primitive leukemic cells that should
      facilitate further analysis of the mechanisms underlying their abnormal
      proliferative behavior.

PMID- 1384788
TI  - Reversible conformational changes induced in glycoprotein IIb-IIIa by a potent
      and selective peptidomimetic inhibitor.
AB  - Platelet glycoprotein (GP) IIb-IIIa inhibitors may become useful antithrombotic
      agents. Ro 43-5054 is a low molecular weight, noncyclic, peptidomimetic inhibitor
      that is three orders of magnitude more potent than RGDS in inhibiting fibrinogen
      binding to purified GPIIb-IIIa and in preventing platelet aggregation.
      Comparisons of RGDS and Ro 43-5054 in cell adhesion assays showed that, in
      contrast to RGDS, Ro 43-5054 was highly selective GPIIb-IIIa inhibitor. Effects
      of RGDV and Ro 43-5054 on the conformation and activation state of GPIIb-IIIa
      were also examined. RGDV and Ro 43-5054 induced conformational changes in
      purified inactive GPIIb-IIIa as determined by binding of the monoclonal antibody
      D3GP3 (D3). These conformational alterations were not reversed after inhibitor
      removal, as indicated by the continued exposure of the D3 epitope and a newly
      acquired ability to bind fibrinogen. Similarly, RGDV and Ro 43-5054 induced
      conformational changes in GPIIb-IIIa on the intact platelet. However, after
      removal of the inhibitors, exposure of the D3 epitope was fully reversed and the
      platelets did not aggregate in the absence of agonist. Thus, while RGD(X)
      peptides and Ro 43-5054 transformed purified inactive GPIIb-IIIa into an
      irreversibly activated conformer, the effects of these inhibitors were reversible
      on the intact platelet. This suggests that factors present in the platelet
      membrane or cytoplasm may regulate in part the ability of the complex to shift
      between active and inactive conformers.

PMID- 1384789
TI  - Enhanced expression of the tie receptor tyrosine kinase in endothelial cells
      during neovascularization.
AB  - We have recently cloned a novel human receptor tyrosine kinase, tie, from human
      leukemia cells showing megakaryoblastoid differentiation. We report here that the
      4.4-kb tie messenger RNA (mRNA) is present in all human fetal and mouse embryonic
      tissues. By in situ hybridization, the tie mRNA was localized to the endothelia
      of blood vessels and endocardium of 9.5- to 18.5-day mouse embryos. However, tie
      was not expressed by endothelial cells of developing hepatic sinusoids. Increased
      tie mRNA signal was seen in proliferating ovarial capillaries during hormone
      induced superovulation. Only a weak tie signal was obtained from adult skin,
      except during wound healing, when the proliferating capillaries in the
      granulation tissue contained abundant tie RNA. These results suggest that tie may
      have a role in neovascularization.

PMID- 1384790
TI  - p55 and p75 tumor necrosis factor receptors in patients with chronic lymphocytic
      leukemia.
AB  - We studied the expression of the two tumor necrosis factor (TNF) receptors, p55
      and p75, on B cells from patients with chronic lymphocytic leukemia (CLL), and
      the presence of soluble TNF receptors in serum. Expression of membrane-associated
      receptors was quantified by double labeling of peripheral blood mononuclear cells
      (PBMC) with monoclonal antibodies against CD19 and p55/p75 TNF receptors and flow
      cytometry. A high fraction of the CD19+ cells expressed the p55 receptor (44% +/-
      34% [SD]) and p75 receptor (61% +/- 31%). In healthy controls, 0% to 1% of the
      CD19+ cells expressed the p55 receptor and 0% to 10% expressed the p75 receptor.
      Incubation of CD19+ cells with 10 ng/mL of TNF increased the incorporation of
      thymidine in 11 patients tested, and this was decreased to 65% (P < .05) by
      antibodies to the p55 receptor or the p75 receptor, and to 35% +/- 7% (P < .001)
      when both antibodies were combined. With an enzyme-linked immunoassay, we
      measured soluble TNF receptors in serum from CLL patients. The mean level of p55
      receptors was increased to 12.9 +/- 8.9 ng/mL (P < .000001 v normal). The mean
      level of p75 receptors was increased to 13 +/- 24 ng/mL (P = .01 v normal). The
      membrane expression of the two receptors was positively correlated (r +/- 97, P <
      .01); however, there was no correlation between membrane expression and serum
      concentration of either receptor. Autologous serum containing high levels of
      soluble TNF receptors inhibited TNF-induced proliferation of CD19+ cells. In
      conclusion, we have demonstrated that neoplastic cells from patients with CLL
      have increased expression of p55 and p75 TNF receptors, and that both receptors
      mediate signal to proliferation. Furthermore, serum from CLL patients has
      elevated levels of soluble TNF receptors, which may counteract the proliferative
      effect of TNF.

PMID- 1384791
TI  - Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid
      and lymphoid lineages.
AB  - FLT3, a receptor belonging to the FMS/KIT family and localized to 13q12, could
      play a role in the biology of early hematopoietic progenitor cells. Because FMS
      and KIT are expressed in both normal progenitors and myeloid leukemias, we looked
      for FLT3 expression in fresh human leukemic cells using Northern blot analysis.
      High levels of FLT3 expression were detected in 92% of the cases of acute myeloid
      leukemia (AML) tested, ranging from the M1 to the M5 stages of differentiation
      assessed in the French-American-British classification. Immature (MO) AML cells,
      biphenotypic leukemias, and AML with megakaryocytic differentiation (M7 subtype)
      also expressed the FLT3 transcript. FLT3 was also expressed at high levels in
      acute lymphoid leukemias of T and B origins. Finally, it was not expressed in
      chronic myeloid leukemias in chronic phase, whereas it was expressed in most
      blast crisis samples. This pattern of expression of FLT3 contrasts with the
      expression of FMS and KIT restricted to myeloid leukemias, and suggests that the
      FLT3 product could play a role in the expansion of the leukemic blasts of both
      the myeloid and lymphoid lineages.

PMID- 1384792
TI  - t(9;14)(p13;q32) denotes a subset of low-grade non-Hodgkin's lymphoma with
      plasmacytoid differentiation.
AB  - In this series of 426 consecutively ascertained, karyotypically abnormal non
      Hodgkin's lymphomas (NHLs) derived from 407 patients, a t(9;14)(p13;q32) was
      encountered in 7 cases; an additional case demonstrated t(9;14)(p1?3;q32). At the
      time of detection of t(9;14), four cases were small lymphocytic lymphomas with
      plasmacytoid features; in three of these the t(9;14) was the sole karyotypic
      abnormality. In two cases of large-cell NHL demonstrating t(9;14), retrospective
      review of prior lymph node biopsies showed the presence of a small lymphocytic
      lymphoma of the plasmacytoid subtype. The remaining two cases comprised a large
      cell lymphoma of the brain and a follicular NHL. Thus, six of eight cases (75%)
      had an initial identical low-grade histology. Immunohistochemical analysis of six
      cases showed no reactivity with CD1, CD2, CD4, CD5, CD8, and CD10 and high
      reactivity with CD19 and CD20. All four lymphocytic lymphomas and one of the two
      large-cell NHLs showed cytoplasmic Ig, consistent with plasmacytoid
      differentiation. Of the eight cases in this series, six presented with or
      developed stage IV disease; all were characterized by a 6-month to 5-year
      clinical phase of indolent disease before treatment was instituted. All five
      patients with low-grade NHL at the time of cytogenetic analysis were alive with
      recurrent disease at 3-year median follow-up. The remaining three patients with
      large-cell diffuse histologies relapsed after intensive therapy and expired at a
      median of 3 years from diagnosis; two of these showed previous or metachronous
      small lymphocytic tumors. These results suggest a novel biologically distinct
      subset of NHL; a neoplasm of mature B lymphocytes with plasmacytoid
      differentiation, characterized by t(9;14); and an indolent presentation followed
      by gradual clinical progression of disease.

PMID- 1384793
TI  - Epstein-Barr virus burden in Hodgkin's disease is related to latent membrane
      protein gene expression but not to active viral replication.
AB  - The Epstein-Barr virus (EBV) has been increasingly detected in Hodgkin's disease
      (HD), but its role in pathogenesis remains uncertain. We analyzed 20 specimens of
      HD known to contain EBV DNA by a sensitive reverse transcriptase polymerase chain
      reaction (RT-PCR). The cases were assessed for the presence of RNA transcripts of
      the BNLF1 gene (coding for the viral latent membrane protein [LMP]) and the late
      replicative gene BLLF1 (coding for the principle envelope glycoprotein
      [gp220/350]). LMP RNA transcripts were found in 9 of 20 (45%) cases, mostly those
      containing many copies of viral DNA and of mixed cellularity (MC) histological
      subtype. Only one LMP RNA-positive case was also positive for RNA transcripts of
      the active replication gene BLLF1. Our results show that viral burden in HD is
      not primarily related to active viral replication, but is associated with LMP
      gene expression.

PMID- 1384794
TI  - Thrombospondin mediates adherence of CD36+ sickle reticulocytes to endothelial
      cells.
AB  - Initiation of vasocclusion in sickle disease pathophysiology may involve abnormal
      red blood cell (RBC) adhesivity to endothelium, a phenomenon influenced by both
      RBC and plasma factors. Using human umbilical vein endothelial cells and a
      gravity sedimentation adherence assay, we have examined thrombospondin (TSP) as a
      plasma factor in this adhesive event. The already-abnormal adherence of sickle
      RBCs in buffer/albumin is significantly augmented (P < .001) by the addition of
      TSP, with half-maximal effect at about 0.3 microgram/mL. This effect is abolished
      by antibodies to either TSP or glycoprotein (GP) IV (CD36), as well as peptides
      RGDS and CSVTCG. The even greater adherence (P < .005) of sickle RBCs in
      autologous platelet-rich plasma (without added TSP) is dramatically inhibited by
      alpha CD36 antibodies (OKM5 and alpha GPIV) and significantly diminished by alpha
      TSP, by peptides RGDS and CSVTCG, and by two antibodies to the vitronectin
      receptor (7E3 and LM609). Studies of density-separated subpopulations and of RBC
      adhesion to immobilized proteins, as well as analysis of sickle RBCs using
      fluorescence-activated cell sorting and single cell microfluorometry, show that
      TSP responsiveness is a feature of the immature sickle "stress" reticulocytes,
      which carry CD36 (and not GPIIbIIIa-like receptors) as the TSP-receptive moiety.
      The endothelial cell's participation in this phenomenon appears to be more
      complex, and the data are consistent with the notion that it involves TSP
      interaction with other plasma proteins and/or multiple receptor structures. Other
      potential adhesogenic proteins (plasma von Willebrand factor, vitronectin,
      fibrinogen, and fibronectin) neither exhibited an affinity for reticulocytes nor
      supported increased sickle RBC adherence when added to buffer/albumin in these
      assay systems. In aggregate, our results indicate that TSP may be the major
      promoter of RBC adhesivity in plasma, and they suggest that therapeutic benefit
      might derive from interference with sickle reticulocyte CD36, as achieved by
      antibodies and CSVTCG in these studies.

PMID- 1384795
TI  - Cell lines produce factors that induce fetal hemoglobin in human BFUe-derived
      colonies.
AB  - Established cell lines were screened for secretion of activities than can
      stimulate fetal hemoglobin (HbF) production in adult burst-forming unit-erythroid
      (BFUe) cultures. Conditioned media from four cell lines, a human teratocarcinoma,
      an osteosarcoma, a bladder cell carcinoma, and feline leukemia virus (FeLV) A
      infected feline fibroblasts (FEF-A cells), consistently increased the relative
      production of fetal globin in BFUe-derived colonies. In vitro translation of RNA
      from these cells in Xenopus oocytes yielded products that increased the gamma to
      gamma+beta ratio in adult erythroid colonies. These results demonstrate that a
      variety of cell lines produce factors that stimulate the production of HbF in
      vitro. The genes of such factors could be isolated by expression cloning of cDNA
      from cell lines using the Xenopus oocyte system.

PMID- 1384796
TI  - The generation of human natural killer cells from CD34+/DR- primitive progenitors
      in long-term bone marrow culture.
AB  - We have adapted the stroma-dependent long-term bone marrow culture (LTBMC) system
      to study the development of human natural killer cells (NK) from the CD34+/HLA-DR
      (CD34+/DR-) BM mononuclear cell (BMMNC) population. The CD34+/DR- population
      does not express any known antigens associated with myeloid or lymphoid lineage
      and has been shown by us and others to contain primitive hematopoietic
      progenitors capable of both self-renewal and differentiation to myeloid lineage.
      CD34+/DR- cells obtained from normal human BM by fluorescence-activated cell
      sorting were plated on allogeneic, irradiated BM stromal layers. After 5 weeks of
      culture in the presence of media containing recombinant interleukin-2 and human
      serum, 147- +/- 21-fold expansion of cells with the morphologic appearance of
      large granular lymphocytes was observed. Cultured cells (84.8% +/- 1.5%)
      expressed the characteristic CD56+/CD3- phenotype of NK. A proportion of
      CD56+/CD3- cells expressed other markers of lymphoid lineage that have been
      associated with mature NK, including CD2 (7.8% +/- 1.2%), CD7 (19.5% +/- 2.8),
      CD8 (3.1% +/- 1.0%), and CD16 (4.5% +/- 1.3%). The cultured cells did not express
      other antigens associated with T-lymphocyte (CD3, CD5, T-cell receptor [TCR]
      alpha/beta and TCR gamma/delta), B-lymphocyte (CD19), myeloid (MY8, CD33, and
      CD71), or monocytoid (CD14 and CD15) lineage and did not express the CD34 antigen
      associated with hematopoietic progenitors present on the starting population.
      This NK population was cytotoxic against both K562 (E:T 20:1; 79% +/- 1.9%) and
      Raji (E:T 20:1; 38% +/- 5.7%) target cell lines. The NK progenitor frequency in
      the CD34+/DR- cell population determined by limiting dilution of CD34+DR- on
      stromal layers followed by a functional chromium release assay against K562
      targets was 1:169 +/- 50 CD34+/DR- cells. The data suggest that human LTBMC
      developed to study myeloid differentiation can be modified to study the origin
      and development of the NK and possibly other lymphoid lineages. Modified cultures
      show that cells with morphologic, phenotypic, and functional characteristics of
      NK can be derived from a population of BMMNC with the phenotype of primitive
      hematopoietic progenitors and without phenotypic evidence of lymphoid- or myeloid
      lineage commitment. Further studies will address the cell of origin and the
      ontogeny of human NK and other lymphoid lineages.

PMID- 1384797
TI  - Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to
      chemotherapy: experience on Pediatric Oncology Group AML Study 8498.
AB  - The treatment of acute myeloid leukemia (AML) in children with Down's syndrome
      (DS) has engendered considerable controversy. Because of the concerns for
      toxicity and increased rate of infections, treatment approaches varied
      considerably in the past with mixed results. However, experience on the recently
      completed Pediatric Oncology Group (POG) 8498 AML study suggests that DS children
      with AML constitute a distinct subgroup that responds well to therapy. Twelve of
      285 children on POG 8498 (protocol for newly diagnosed AML) had DS. Children with
      DS and AML were predominantly male (9 of 12) and were quite younger at diagnosis
      (< 24 months in 10). The white blood cell count was less than 50 x 10(3)/microL
      in all 12 and French-American-British types M6 and M7 were frequent (5 of 12). An
      abnormal cytogenetic marker, in addition to constitutional trisomy 21, was
      present in 9 of 12 and involved chromosome 8 in 4 of 9. All cases studied (n = 5)
      were positive for myeloid cell surface markers (CD33, CD13, or CD11b) and,
      interestingly, were also positive for the CD7 antigen. Chemotherapy included
      daunorubicin, cytarabine (Ara-C), and 6-thioguanine for remission induction and
      featured high-dose Ara-C (3 g/m2 per dose) with or without L-asparaginase early
      in remission. Compared with children without DS, children with DS had a superior
      event-free survival (EFS at 4 years 100% v 28% +/- 6.2%; P = .003). The EFS
      remained superior even when compared with non-DS children less than 2 years of
      age with a white blood cell count less than 10 x 100,000/microL (100% v 48% +/-
      17.3%; P = .01).

PMID- 1384798
TI  - Stem cell factor directly stimulates the development of enriched granulocyte
      macrophage colony-forming cells and promotes the effects of other colony
      stimulating factors.
AB  - The effects of the c-kit ligand (stem cell factor [SCF]) on the development of a
      highly enriched population of granulocyte-macrophage colony-forming cells (GM
      CFC) were assessed. In soft agar assays, both in serum-containing and in serum
      deprived cultures, SCF promoted the formation of colonies that contained
      predominantly granulocytic cells with some blast cells also present. The size of
      these colonies was far smaller than observed in the presence of interleukin-3 (IL
      3). In serum-deprived conditions, no colonies were formed in the presence of
      macrophage colony-stimulating factor (M-CSF), but when M-CSF was combined with
      SCF, a marked change was noted in that large colonies were produced containing
      predominantly macrophages. When GM-CFC were cultured in the presence of IL-3 and
      SCF, colonies were formed that contained blast cells, granulocytes, and
      macrophages. A synergistic interaction was also seen using a combination of G-CSF
      plus SCF in either serum-containing or serum-deprived cultures. The addition of
      SCF to colony-forming assays markedly reduced the concentration of IL-3 or G-CSF
      required for optimal levels of colony formation. Furthermore, SCF was capable of
      promoting the survival of GM-CFC for several days, after which large colonies
      containing mature cells were formed upon the addition of a secondary growth
      factor such as G-CSF or IL-3. Thus, SCF can directly act on highly enriched
      committed progenitor cells in serum-deprived conditions to promote survival,
      proliferation, and development.

PMID- 1384799
TI  - Induction of differentiation of human mast cells from bone marrow and peripheral
      blood mononuclear cells by recombinant human stem cell factor/kit-ligand in long
      term culture.
AB  - In the murine system, a number of cytokines (including interleukin-3 [IL-3], IL
      4, and stem cell factor [SCF]) promote the growth of mast cells (MCs). However,
      so far little is known about factors controlling differentiation of human MCs.
      Recent data suggest that human MCs express receptors (R) for SCF. The aim of the
      present study was to investigate whether recombinant human (rh) SCF induces
      differentiation of human MCs from their precursor cells. For this purpose, bone
      marrow (BM; normal donors, n = 6) and peripheral blood (PB; normal donors, n =
      11) mononuclear cells (MNC) were cultured in the presence of rhSCF, rhIL-3, rhIL
      4, rhIL-9, recombinant human macrophage colony-stimulating factor (rhM-CSF), or
      control medium in long-term (8 weeks) suspension cultures. After 4 weeks, up to
      5% of the MNC (BM and PB) cultured in the presence of rhSCF, but not in the
      presence of other cytokines, were found to exhibit the characteristics of MCs.
      These MCs expressed the YB5.B8-reactive domain of the SCF R as well as IgE R, as
      determined by combined toluidine blue/immunofluorescence staining. Myeloid
      antigens, likewise expressed on human basophils (ie, CD11b, CDw65, and Bsp-1),
      could not be detected on these cells. Furthermore, rhSCF, but not rhIL-3, rhIL-4,
      rhIL-9, or rhM-CSF, induced dose- and time-dependent increases in the formation
      of cellular tryptase (an MC-specific enzyme) (rhSCF [100 ng/mL], 1,308 +/- 679
      ng/mL v control medium, 18 +/- 6 ng/mL tryptase on day 35 of PB cell cultures),
      as well as an increase in cellular histamine. After 6 to 8 weeks, when other
      mature hematopoietic cells decreased, MCs still could be detected in culture,
      with up to 40% of all cells being MCs. To test whether rhSCF also activates
      tissue MCs, we performed histamine release experiments (dispersed tissue; lung, n
      = 3; uterus, n = 3). SCF was found to enhance (by up to 3.4-fold) the capacity of
      the MCs to release histamine upon cross-linkage of IgE R with anti-IgE. Together,
      these observations suggest that rhSCF induces in vitro differentiation of human
      MCs from their BM and PB precursor cells in long-term culture and upregulates MC
      releasability.

PMID- 1384800
TI  - Retinoic acid inhibits interleukin-6-induced macrophage differentiation and
      apoptosis in a murine hematopoietic cell line, Y6.
AB  - We established a radiation-induced murine hematopoietic cell line, Y6, that could
      be induced to differentiate into macrophages by interleukin-6 (IL-6). IL-6 also
      induced growth inhibition and apoptosis in Y6 cells. Retinoic acid (RA) inhibited
      such effects of IL-6 on Y6 cells. The inhibitory effect of RA on the effects of
      IL-6 was not caused by the downregulation of the IL-6 receptor, because RA
      neither affected the expression of IL-6 receptor mRNA nor the expression of IL-6
      receptor molecule on the cell surface. Furthermore, RA did not inhibit the IL-6
      induced expression of junB mRNA, indicating that the expression of functionally
      active IL-6 receptor and the signal transduction pathway activating the junB gene
      are not inhibited by RA. IL-6-induced macrophage differentiation of Y6 cells was
      preceded by the downregulation of the c-myc gene, which was also prevented by RA.
      Because the inhibitory effect of RA on Y6 cells was reversible and seemed not to
      require de novo protein synthesis, the RA receptor by itself might be directly
      involved in the inhibition of the IL-6 signal transduction pathway. The results
      indicated that the IL-6 signal transduction pathways leading to the induction of
      macrophage differentiation and junB gene expression can be dissected by RA.

PMID- 1384802
TI  - Potential of phenylalanine methylester as a bone marrow purging agent.
AB  - Phenylalanine methylester (PME), a lysosomotropic compound can be used to deplete
      monocytes and myeloid cells from peripheral blood and bone marrow (BM). The
      potential of PME for purging leukemic cells from BM was investigated using U937
      and HL-60 cell lines as models. Optimal purging conditions for U937 cells were
      determined using an MTT assay (3-4, 5-dimethylthiazol-2, 5-diphenyl tetrazolium
      biomide; Sigma). Elimination of U937 cells was time-, temperature-, and dose
      dependent. PME activity was optimal at 37 degrees C for 45 minutes. Depletion of
      U937 was > 2.8 logs for 50 mmol/L PME. Compared with another purging agent, 100
      micrograms/mL 4-hydroperoxycyclophosphamide had activity comparable to 40 mmol/L
      PME. HL-60 cells were even more sensitive to PME than U937 cells. To support
      observations made with the MTT assay, clonogenic assays were performed. PME, 50
      mmol/L at 37 degrees C resulted in total depletion (> 5 logs) of U937 colonies.
      Progressive depletion of normal progenitor cells occurred when BM was incubated
      with PME at concentrations from 5 to 100 mmol/L. At 37 degrees C, 50 mmol/L PME
      reduced colony-forming units-granulocyte-macrophage and burst-forming units
      erythroid (BFU-E) recovery by 98%. Recombinant human mast cell factor augmented
      BFU-E after PME treatment but had no effect on HL-60 or U937. These studies
      suggest that PME deserves further study as an agent for ex vivo marrow purging.

PMID- 1384801
TI  - The antitumor activity of an anti-CD22 immunotoxin in SCID mice with disseminated
      Daudi lymphoma is enhanced by either an anti-CD19 antibody or an anti-CD19
      immunotoxin.
AB  - The antitumor activities of immunotoxins (ITs) constructed with deglycosylated
      ricin A chain (dgA) and either anti-CD19 (HD37) or anti-CD22 (RFB4) monoclonal
      antibodies were compared in SCID mice with disseminated human Daudi lymphoma
      (SCID/Daudi). As reported previously, after intravenous injection with Daudi
      cells, SCID mice develop disseminated lymphoma, which infiltrates the vertebral
      column and causes paralysis of the hind legs before death. The mean paralysis
      time (MPT) has been taken as an end point in this tumor model. We have previously
      reported that early treatment of SCID/Daudi mice with RFB4 coupled to dgA
      prolongs the MPT in a manner consistent with the killing of 4 logs of tumor
      cells. In the present study, we show that HD37-dgA kills 2 logs of tumor cells.
      The lower potency of the HD37-dgA is consistent with its lower IC50 on Daudi
      cells in vitro. We further show that the antitumor activity of a mixture of HD37
      dgA and RFB4-dgA is significantly enhanced in SCID/Daudi mice and is consistent
      with the killing in excess of 5 logs of tumor cells. However, identical
      enhancement was observed when a mixture of the RFB4-dgA and the HD37 antibody was
      administered. In contrast, enhancement was not observed when mice were injected
      with a mixture of the RFB4 antibody and the HD37-dgA. The results indicate that a
      "cocktail" of HD37 antibody and RFB4-dgA immunotoxin can have significant
      antitumor activity in this mouse model of lymphoma and suggest that combinations
      of particular antibodies and ITs may have cooperative antitumor activity.

PMID- 1384803
TI  - NCAM (CD56)-positive malignant lymphoma.

PMID- 1384805
TI  - The insulin-like growth factor binding proteins (IGFBPs) in human breast cancer.
AB  - Several lines of evidence suggest that IGFs are important regulators of breast
      cancer cell growth. Unlike other growth factors, the IGFs interact with specific
      binding proteins in all extracellular fluids. To date, six different IGFBPs have
      been cloned, although their exact physiological function is not understood.
      Experimental evidence accumulated over the past few years suggests that IGFBPs
      could function as modulators of IGF actions in a variety of systems. This
      includes breast cancer, since several groups have demonstrated the production of
      IGFBPs by human breast cancer cells. We have found that the pattern of expression
      of these binding proteins is heterogeneous and varies depending on the breast
      cancer cell ER status. We have also shown that estrogen is capable of regulating
      the expression of certain IGFBPs in MCF-7 cells. Specifically, estradiol enhanced
      the expression of IGFBP 2, 4, and 5, and decreased that of IGFBP-3 in this cell
      line. Since the IGFBPs can modulate IGF actions in different experimental
      systems, we and others have studied their potential role as inhibitors of IGF
      induced mitogenesis in breast cancer cells. We have demonstrated that purified
      IGFBP-1 neutralized IGF-dependent growth of MCF-7 cells in a reversible manner.
      These results suggest that the IGFBPs might be used to inhibit IGF-mediated
      breast cancer proliferation.

PMID- 1384806
TI  - The retinal cells generating the circadian small spikes in the Bulla optic nerve.
AB  - A circadian rhythm in the frequency of compound action potentials (CAPs) in the
      optic nerve of the mollusc Bulla gouldiana is believed to be generated by the
      basal retinal neurons (BRNs) of the eye. Along with the CAPs, which are about 100
      microV in amplitude, there are 10- to 40-microV impulses from an undetermined
      cell type in records from the optic nerve. These impulses, called "small spikes,"
      are generated spontaneously in darkness and show a circadian rhythm in frequency
      that is about 12 hr out of phase with the CAP rhythm. To enable us to determine
      the origin of the small spikes, intracellular recordings were made from retinal
      cells while optic nerve activity was monitored. The cells were identified by
      their light responses and then injected with the fluorescent dye Lucifer Yellow
      CH or the tracer biocytin. It was found that the large photoreceptors of the
      distal retina generated graded depolarizations in response to light, and had
      axons in the optic nerve, but did not show impulses at the level of the
      photoreceptor layer. By contrast, the spiking retinal cells of the photoreceptor
      layer generated depolarizations and impulses in response to light. In addition,
      the spiking cells were found to be dye-coupled to a series of retinal cells
      approximately 7 microns in diameter, connected to a single axon in the optic
      nerve. Impulses from the spiking cells occurred spontaneously and correspond with
      the small spikes in the optic nerve. The BRNs appear to inhibit the retinal cells
      that generate the small spikes. Hyperpolarization of the BRNs, through constant
      current injection, increased the number of small spikes in the optic nerve.
      Release from hyperpolarization led to a decrease in small spikes. This could
      explain how circadian changes in BRN membrane potential might modulate
      spontaneous firing of the spiking cells, resulting in the circadian rhythm in
      small-spike frequency.

PMID- 1384807
TI  - Synergism of chlorpyrifos against the German cockroach, Blattella germanica.
AB  - Of fifteen compounds tested as synergists for chlorpyrifos against susceptible
      and resistant strains of Blattella germanica, the German cockroach, eleven were
      active against the resistant strain but only seven were synergistic against the
      susceptible strain. Overall, the most effective synergist was S,S,S-tributyl
      phosphorotrithioate (DEF) followed by phenyl saligenin cyclic phosphonate (PSCP)
      and two substituted N,N-dimethylcarbamates: SK-102 and SK-37. The most effective
      synergist for overcoming chlorpyrifos resistance was SK-37 which reduced the
      resistance ratio by 3.2-fold. Four other synergists which reduced chlorpyrifos
      resistance, in order of their effectiveness, were: SK-102 > PSCP > DEF >
      tridiphane. The potential usefulness of these synergists for German cockroach
      control is discussed.

PMID- 1384804
TI  - The insulin-like growth factor family of ligands, receptors, and binding
      proteins.
AB  - The insulin-like growth factors (IGFs) have important roles in normal cellular
      growth and development. The IGFs have also been implicated in regulation of tumor
      cell growth. Two ligands, IGF-I and IGF-II, have been identified that are
      expressed in both fetal and adult tissues. They interact with at least two
      specific cell surface receptors. The type I IGF receptor is homologous to the
      insulin receptor in structure and has tyrosine kinase activity. The type II
      receptor is identical to the mannose-6-phosphate receptor known to be important
      in the trafficking of lysosomal enzymes; its role in IGF signal transduction is
      not clear. Furthermore, a hybrid receptor composed of subunits from the insulin
      receptor and the type I IGF receptor have been identified. In addition to these
      receptors, six different IGF binding proteins have been identified, which
      modulate the activity of the IGFs in various ways. Thus, there is great potential
      for complex interactions between the family members that could ultimately
      regulate normal and neoplastic cell growth.

PMID- 1384808
TI  - Embryonic expression and functional analysis of a Xenopus activin receptor.
AB  - We report the isolation and characterization of a Xenopus activin receptor
      (XAR1). The amino acid sequence of this protein shows extensive homology with a
      murine activin receptor. The mRNA is expressed maternally and is ubiquitously
      distributed during the early stages of embryogenesis. Consistent with a possible
      role in mesoderm induction and patterning, interference with the normal
      expression of the receptor by overexpression in the early embryo results in the
      formation of ectopic dorsal axial structures. During neurulation the XAR1 mRNA is
      expressed predominantly in the presumptive brain and spinal cord, suggesting an
      additional function for XAR1 in neurogenesis.

PMID- 1384809
TI  - Effects of lithium chloride and retinoic acid on the expression of genes from the
      Xenopus laevis Hox 2 complex.
AB  - We show that Xenopus laevis has a Hox 2 complex, and that this complex is
      strongly conserved with the mammalian one, both in structure and in the rules of
      spatial and temporal sequential expression of its genes during the early stages
      of development. Lithium chloride and retinoic acid, two reagents known to alter
      axial patterning of the body when applied to Xenopus embryos, produce,
      respectively, embryos with reduced posterior but exaggerated anterior structures
      and embryos with truncation of anterior structures. We report here on the effect
      of these reagents on the expression of Hox 2 genes in the Xenopus embryos. LiCl
      has a dramatic effect on Hox genes, suppressing the expression of these genes
      during gastrulation and early neurulation. However, later on expression of these
      genes reaches significant levels, suggesting the existence of two phases in the
      control of Hox gene expression. Retinoic acid increases the steady state level of
      transcripts from Hox genes with the greatest effect on Hox 2.7, the most anterior
      of the genes studied. This suggests that the results obtained in EC cells
      (Simeone et al., 1990, 1991) reflect what occurs in vivo. Neither LiCl nor RA
      change the sequential order of the onset of expression of the genes, showing that
      these reagents do not perturb the molecular mechanisms used to establish the
      sequential activation of the genes of the Hox complexes.

PMID- 1384811
TI  - Immunocytochemical localization of cell adhesion molecules in the developing and
      mature olfactory system.
AB  - The localization of Ca+(+)-independent cell adhesion molecules (CAMs) in the
      developing and mature olfactory epithelium and bulb is reviewed. The CAMs
      included in this article are the neural cell adhesion molecule (N-CAM), the 180
      kD component of N-CAM (N-CAM 180), the embryonic form of N-CAM (E-N-CAM), L1
      glycoproteins, J1 glycoproteins, and the adhesion molecule on glia (AMOG). In
      addition, the expression of the L2-HNK-1 carbohydrate epitope, shared by N-CAM,
      L1, J1 and myelin-associated glycoprotein (MAG) in the adult olfactory epithelium
      and bulb has also been documented. For the localization of these molecules at the
      light and electron microscopic levels, immunocytochemical techniques were used
      and are described in detail. During development and organogenesis, the olfactory
      system exhibits a pattern of CAM expression similar to the general pattern
      described for the developing nervous system. In the adult olfactory system,
      however, a significant retention of CAMs characteristic for developmental and
      morphogenetic processes, such as E-N-CAM, AMOG, as well as the high molecular
      weight components of J1 glycoproteins, can be observed. The retention of these
      embryonic features are most likely associated with the cell turnover and high
      plasticity of this system. Moreover, the predominance of N-CAM 180 with respect
      to other components of N-CAM, as well as the absence of the L2/HNK-1 carbohydrate
      epitope, are also particular traits of the primary olfactory system which could
      be associated with its exceptional properties.

PMID- 1384812
TI  - Proceedings of the 13th National Meeting of the Italian Society for The Study of
      The Connective Tissue. Bologna, 18-19 September 1992.

PMID- 1384810
TI  - Coordinated induction of cell proliferation and syndecan expression in dental
      mesenchyme by epithelium: evidence for diffusible signals.
AB  - Epithelial-mesenchymal interactions induce the expression of syndecan, a cell
      surface proteoglycan, and tenascin, an extracellular matrix glycoprotein in the
      mesenchymal component of many organ rudiments including the tooth. Experimental
      recombination cultures of early dental epithelium and mesenchyme were analysed by
      double immunostaining to compare the distribution of syndecan, tenascin, and
      proliferating cells (BrdU incorporation) in the induced dental mesenchyme. After
      5-9 hr in culture expression of syndecan and tenascin as well as an increase in
      BrdU incorporation were evident in the mesenchymal cells adjacent to the
      epithelium and the positive area enlarged with time. Syndecan and tenascin were
      colocalized only partially in some explants. The expression of syndecan and
      tenascin in the recombinants correlates with their stage-dependent expression
      pattern during early tooth development in vivo (Vainio and Thesleff, 1992). The
      area of increased cell proliferation in the mesenchyme correlated closely with
      syndecan expression. In none of the explants was increased BrdU incorporation
      observed in syndecan negative areas. Epithelium induced also condensation of the
      mesenchymal cells. Induction and spread of the syndecan-positive zone in the
      dental mesenchyme required close and continuous contact with the epithelium. The
      mechanism by which the induction of syndecan expression spreads in the mesenchyme
      was studied in rat-mouse interspecies recombination cultures, using syndecan
      antibodies that recognize mouse but not rat syndecan. The rat mesenchyme and
      epithelium were first cultured in contact for 24 hr. Then the epithelium was
      removed and freshly dissected, "uninduced" mouse mesenchyme was placed in contact
      with different aspects of the rat mesenchyme. The rat mesenchymal cells that had
      located next to the epithelial tissue stimulated syndecan expression in adjacent
      mouse mesenchyme. The induction potential was gradually lost toward the periphery
      of the rat mesenchyme. Based on these findings we suggest that diffusible signal
      molecules mediate the spread of syndecan induction in the mesenchyme and that
      syndecan plays a role in the regulation of cell proliferation.

PMID- 1384813
TI  - Mapping of RNA polymerase on mammalian genes in cells and nuclei.
AB  - The assembly of an RNA polymerase II initiation complex at a promoter is
      associated with the melting of the DNA template to allow the polymerase to read
      the DNA sequence and synthesize the corresponding RNA. Using the specific single
      stranded modifying reagent KMnO4 and a new genomic sequencing technique, we have
      explored the melted regions of specific genes in genomic DNA of whole cells or of
      isolated nuclei. We have demonstrated for the first time in vivo the melting in
      the promoter proximal transcribed region that is associated with the presence of
      RNA polymerase II complexes. An interferon-inducible gene, ISG-54, exhibited
      KMnO4 sensitivity over approximately 300 nucleotides downstream of the RNA
      initiation site in interferon-treated cells when the gene was actively
      transcribed but not in untreated cells where the gene was not transcribed. The
      extent of KMnO4 modification was proportional to transcription levels. The KMnO4
      sensitivity was retained when nuclei were isolated from induced cells but was
      lost if the engaged polymerases were further allowed to elongate the nascent RNA
      chains ("run-on"). The sensitivity to KMnO4 in isolated nuclei was retained if
      the run-on incubation was performed in the presence of alpha-amanitin, which
      blocks progress of engaged polymerases. A similar analysis identified an open
      sequence of only approximately 30 bases just downstream of the start site of the
      transthyretin (TTR) gene in nuclei isolated from mouse liver, a tissue where TTR
      is actively transcribed. This abrupt boundary of KMnO4 sensitivity, which was
      removed completely by allowing engaged polymerases to elongate RNA chains,
      suggests that most polymerases transcribing this gene paused at about position
      +20. The possibility of mapping at the nucleotide level the position of actively
      transcribing RNA polymerases in whole cells or isolated nuclei opens new
      prospects in the study of transcription initiation and elongation.

PMID- 1384814
TI  - Escherichia coli ribonucleotide reductase expression is cell cycle regulated.
AB  - The expression of the genes encoding ribonucleotide reductase in Escherichia coli
      was investigated in cultures synchronized by obtaining the smallest cells in a
      population after sucrose gradient centrifugation. Specific activity of
      ribonucleotide reductase and DNA initiation were found to increase in parallel,
      periodically as a function of the cell cycle. The expression of nrd was also
      determined in cells synchronized by periodic repeated doubling in a phosphate
      limited medium. Antibodies directed against the B2 subunit of ribonucleotide
      reductase were raised in a rabbit and purified. Immunoprecipitation of the B2
      subunit and RNA-DNA dot blot hybridization assays were developed and employed to
      determine the expression of ribonucleotide reductase translational and
      transcriptional products during the cell cycle. Both of nrd-mRNA and B2 subunit
      expression were found to increase each generation at approximately the same time
      DNA synthesis was initiated and then to decrease back to the basal level shortly
      after DNA initiation. These results provided evidence of cell cycle dependent
      regulation of ribonucleotide reductase in E. coli. When the upstream regulatory
      region of nrd was fused to a promoterless lacZ gene on a single copy plasmid, lac
      mRNA and beta-galactosidase were found to be synthesized in parallel to nrd
      expression from the chromosomal operon. When nrd sequences surrounding the
      promoter were removed from this construct, lac-mRNA and beta-galactosidase
      synthesis were no longer cell cycle regulated.

PMID- 1384815
TI  - The effect of the immunophilin ligands rapamycin and FK506 on proliferation of
      mast cells and other hematopoietic cell lines.
AB  - The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of
      activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from
      mast cells and T cell receptor-mediated transcription of IL-2. These findings
      suggest a common step in receptor-mediated signal transduction leading to
      exocytosis and transcription and imply that immunosuppressive drugs target
      specific signal transduction pathways, rather than specific cell types. This
      hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent
      proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation
      of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is
      prevented in a competitive manner by FK506, a structural analogue of rapamycin.
      Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also
      inhibited, at doses comparable to those shown previously to inhibit IL-2
      dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast,
      proliferation of A-431 cells, a epidermoid cell line, was not affected by
      rapamycin. DNA histograms indicate that complexes formed between the rapamycin
      FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the
      G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit
      proliferative signals emanating from IL-3 receptors, resulting in growth arrest
      of cytokine-dependent, hematopoietic cells.

PMID- 1384817
TI  - Use of granulocyte colony-stimulating factor in the treatment of pancytopenia
      secondary to colchicine overdose.
AB  - OBJECTIVE: To report a case of pancytopenia following colchicine overdose and to
      discuss the use of granulocyte colony-stimulating factor (G-CSF) for treating
      this severe complication. CASE SUMMARY: A 19-year-old man developed pancytopenia
      four days after ingestion of approximately 50-60 0.6-mg colchicine tablets in a
      suicide attempt. His pancytopenia resolved after subcutaneous administration of
      one 300-micrograms dose of G-CSF. The patient recovered from his other multiorgan
      disturbances during his hospitalization and was discharged from the hospital with
      elevated liver enzyme concentrations. CONCLUSIONS: Colchicine overdose is rare,
      but can be fatal. The use of G-CSF appears to be beneficial in alleviating bone
      marrow depression in colchicine overdose situations.

PMID- 1384816
TI  - The effect of low-density lipoprotein apheresis on plasma thrombomodulating
      factors.
AB  - The authors have investigated the effects of double-membrane filtration with
      hollow fiber membranes made of different artificial materials and low-density
      lipoprotein (LDL)-adsorbent dextran sulfate cellulose (DS) columns on coagulation
      related proteins and complement components to evaluate their hemocompatibility.
      All membrane filters showed similar sieving effects, which depended upon the
      molecular weights of the proteins. In the double-membrane filtration system, free
      protein S, protein C, antithrombin III, and alpha 1-antitrypsin were returned to
      the intracorporeal circulation, whereas alpha 2-macroglobulin and fibrinogen were
      almost completely removed from the circulation; C4b-binding protein (C4BP)
      protein S complexes were also trapped by the second membrane, and in some
      instances were even blocked by the first membrane, if it was made of material
      that activated the classic pathway of the complement system. The DS column
      adsorbed C4BP-protein S complex, but free protein S was almost completely
      recovered in the eluate.

PMID- 1384818
TI  - Effects of dexamethasone on the production of insulin-like growth factor-I and
      insulin-like growth factor binding proteins in primary cultures of rat
      hepatocytes.
AB  - The effects of dexamethasone (Dex) on insulin-like growth factor (IGF)-I and IGF
      binding protein (IGFBP)-1 production were investigated in primary cultures of rat
      hepatocytes. Dex enhanced the secretion of IGFBP-1 as measured by ligand blot
      analysis but did not show any prominent effect on immunoreactive IGF-I secretion.
      EC50 of Dex on IGFBP-1 secretion was calculated to be 3 x 10(-8) M. The content
      of IGFBP-1 mRNA in the cells increased greatly in the presence of Dex but the IGF
      I mRNA content did not change significantly under the same conditions. Insulin
      showed the opposite effect of Dex by decreasing the production of IGFBP-1 and the
      cellular content of IGFBP-1 mRNA. This effect of insulin was observed also with
      Dex in the medium. These results show that the gene expression of IGF-I and IGFBP
      1 is differently regulated by glucocorticoids and insulin in primary cultures of
      rat hepatocytes. The results most possibly explain the in vivo effects of
      glucocorticoids and insulin in regulation of IGF-I and IGFBP-1 production by
      liver.

PMID- 1384820
TI  - Further characterization of the interaction between L-selectin and its
      endothelial ligands.
AB  - L-Selectin is a lectin-like receptor on lymphocytes which mediates their
      attachment to high endothelial venules (HEV) within lymph nodes. Previous work
      has identified HEV-associated endothelial ligands for L-selectin as sialylated,
      fucosylated and sulphated glycoproteins of approximately 50 kDa and approximately
      90 kDa (Sgp50 and Sgp90). The interaction of L-selectin with these ligands is
      carbohydrate directed, reflecting the involvement of its amino-terminal, calcium
      type lectin domain. It has been reported, and we have confirmed, that anti-Ly22
      blocks the adhesive function of L-selectin without reducing its binding to a
      carbohydrate- based ligand PPME (phosphomannan monoester core from Hansenula
      hostii). The epitope for this monoclonal antibody depends on the epidermal growth
      factor (EGF) domain of L-selectin. We demonstrate that anti-Ly22 inhibits the
      interaction of L-selectin with both of the Sgps, thus establishing that the
      interaction of L-selectin with HEV can be accounted for by the Sgps. Furthermore,
      the interaction of trypsin fragments of Sgp50 with L-selectin is inhibitable both
      by an antibody that maps to the lectin domain and by anti-Ly22. These findings
      raise the possibility that anti-Ly22 is affecting the function of the lectin
      domain of L-selectin rather than directly antagonizing the EGF domain. Toward a
      further characterization of L-selectin's carbohydrate specificity, we show that
      Sgp50 is partially inactivated by the linkage-specific Newcastle Disease virus
      sialidase (alpha 2,3 linkage). We additionally demonstrate that a sialyl Lewis x
      related tetrasaccharide can interact with L-selectin, as has also been
      demonstrated for E-selectin and P-selectin.

PMID- 1384819
TI  - Murine beta 1,4-galactosyltransferase: round spermatid transcripts are
      characterized by an extended 5'-untranslated region.
AB  - We have previously shown that the expression of the gene encoding murine beta 1,4
      galactosyltransferase (beta 1,4-GT, UDP-galactose:N-acetyl-D-glucosaminyl
      glycopeptide 4-beta-D galactosyltransferase, EC 2.4.1.38) is fundamentally
      different between somatic and male germ cells (Shaper et al., 1990b). In somatic
      cells, two transcripts of 3.9 kb and 4.1 kb are produced. In contrast, in
      spermatogonia only the 4.1 kb transcript is expressed. Maturation of
      spermatogonia to pachytene spermatocytes is accompanied by reduced expression of
      the 4.1 kb transcript to barely detectable levels. Continued differentiation to
      haploid round spermatids is coincident with renewed expression in which the 4.1
      kb transcript is replaced by two truncated transcripts of 2.9 and 3.1 kb. In this
      study, we report the characterization of a full-length beta 1,4-GT cDNA clone
      from a murine round spermatid library that corresponds to the 2.9 kb transcript.
      This transcript encodes the same open reading frame as the 4.1 kb transcript, but
      utilizes alternative poly(A) signals embedded within the long 3'-untranslated
      region of the somatic transcript. Based on sequence analysis, together with
      primer extension and S1 nuclease protection experiments, both the 2.9 and the 3.1
      kb round spermatid beta 1,4-GT transcripts are distinguished by the presence of
      an additional 5'-untranslated sequence of approximately 560 bp that is absent in
      premeiotic germ cells and somatic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384821
TI  - Identification of phosphotyrosine residues in peptides by high performance liquid
      chromatography on-line derivative spectroscopy.
AB  - A method has been developed for the detection of phosphotyrosine residues in
      peptides based on reversed phase-high performance liquid chromatography (RP-HPLC)
      on-line spectral analysis. It has been found that tyrosine-containing peptides
      show a hypsochromic shift of the aromatic absorbance maximum when the tyrosine is
      phosphorylated. Subsequent second-order derivative spectra likewise reveal a
      hypsochromic shift of the corresponding minima of the phosphotyrosine residues
      compared to the unmodified tyrosine. This method allows mapping of tyrosine
      phosphorylation sites in proteins after cleavage into smaller peptides and
      separation and on-line spectral analysis of the latter by RP-HPLC. It furthermore
      provides a useful way for the characterization of synthetic phosphotyrosine
      containing peptides.

PMID- 1384822
TI  - Somatostatin-gene expression in the postmortem adult and fetal human brain.
AB  - We have examined the utility of in situ hybridization for detecting pre
      prosomatostatin mRNA in postmortem human brain. In preliminary studies, Northern
      blot analysis using a rat model, which simulates the normal pattern of human post
      mortem brain cooling, revealed retention of significant amounts of hybridizable
      somatostatin mRNA relative to control levels between 12 and 24 hours after death.
      mRNA extracted from postmortem fetal human brain specimens showed hybridization
      to cRNA probes directed against pre-prosomatostatin mRNA. We thus undertook in
      situ hybridization studies. Antisense RNA probes were hybridized to neurons that
      expressed pre-prosomatostatin in 10-microns sections of adult and fetal human
      brain. The distribution of pre-prosomatostatin mRNA-containing neurons was
      similar to that observed for somatostatin-like immunoreactivity; however, the in
      situ hybridization technique was a more sensitive marker of neuronal perikarya.
      Our results indicate that hybridization to pre-prosomatostatin mRNA is a useful
      method for localizing these peptidergic neurons in postmortem human brain tissue.

PMID- 1384823
TI  - Toleration of amino acid substitutions within hepatitis B virus envelope protein
      epitopes established by peptide replacement set analysis. II. Region S(122-136).
AB  - The envelope of the hepatitis B virus (HBV) consists of three related proteins,
      designated S-, M- and L-protein, all of which share a common 226-amino acid
      residue sequence, corresponding to the S-protein that is sufficient for eliciting
      protective immunity against HBV. HBV variants, resulting from point mutations
      leading to replacements of amino acids within the S(122-160) segment of S
      protein, have been recently recognized. In order to assure the continued success
      of vaccination against HBV and the adequacy of diagnostic tests for HBV envelope
      antigens and antibodies, it is necessary to understand the impact of amino acid
      replacements on the immunological recognition of S-protein at both the B- and T
      cell levels. Immunologically tolerated and forbidden amino acid replacements
      within the S(139-147) segment of S-protein have already been discerned. The
      impact of amino acid substitutions within the S(122-136) segment on the
      immunological recognition of S-protein is analyzed in this report. Such
      replacements do not appreciably affect the binding of rabbit and goat anti-S
      antibodies to replacement set peptides, while decreased murine antibody binding
      was observed with some peptides having substitutions at residues 122, 123 and
      133. On the other hand, amino acid substitutions within the (126-136) region,
      except those distinguishing serological subtypes of HBV from each other,
      abrogated murine T-cell proliferative responses to the peptides, while
      substitutions at residues 122, 123 and 125 had a lesser effect. Some of the
      peptides with amino acid substitutions peculiar to the variants had diminished
      stimulatory activity for T-cells from individuals vaccinated against hepatitis B.
      Amino acid substitutions in both the S(139-147) and S(122-136) segments of S
      protein may potentially result in variant viruses escaping immunological
      surveillance based on current hepatitis B vaccines.

PMID- 1384824
TI  - Acute toxicity of pesticides to Gobius sp., Palaemonetes africanus, and
      Desmocaris trispimosa.

PMID- 1384825
TI  - Effect of aprotinin on metastasis of Lewis lung tumor in mice.
AB  - Kallikrein activity in human stomach tissue was measured and found to be about
      threefold higher in cancer tissue than in normal tissue. To clarify the
      physiological role of this tissue kallikrein, we investigated its effects on the
      spontaneous metastasis and tumor growth of Lewis tumors (3LL). Antiprotease,
      aprotinin, and gabexate mesilate (FOY) inhibited spontaneous metastasis but did
      not inhibit tumor growth, while tissue kallikrein and plasmin enhanced the
      spontaneous metastasis of 3LL. The results suggest that the inhibitory effects of
      aprotinin and FOY on metastasis are not only due to an inhibition of tumor cells
      released by tissue kallikrein, but that tissue kallikrein, a protease, also
      participates in metastasis. We thus conclude that aprotinin or FOY should be
      administered either before or immediately after operation to inhibit spontaneous
      metastasis.

PMID- 1384826
TI  - Protease inhibitors in bronchoalveolar lavage fluid from neonates with special
      reference to secretory leukocyte protease inhibitor.
AB  - An imbalance of proteolytic enzymes and protease inhibitors may contribute to the
      development of bronchopulmonary dysplasia. We studied secretory leukocyte
      protease inhibitor (not previously addressed), and alpha 1-antitrypsin, alpha 1
      antichymotrypsin, alpha 2-macroglobulin and elastase. Albumin was used as an
      internal reference. Infants with pneumonia had higher concentrations of secretory
      leukocyte protease inhibitor (p = 0.02) and elastase (p = 0.04) in
      bronchoalveolar lavage fluid than those with respiratory distress syndrome; those
      who also developed bronchopulmonary dysplasia had intermediate values. A
      decreased concentration of alpha 1-antitrypsin was found in the second and third
      postnatal weeks (p = 0.002). Further detailed studies of the balance between
      proteases and protease inhibitors and of the importance of pulmonary infections
      in the pathogenesis of bronchopulmonary dysplasia are suggested. Secretory
      leukocyte protease inhibitor is important both as an elastase inhibitor of
      bronchial mucus and as a marker of infection in the bronchi.

PMID- 1384827
TI  - Neurodevelopmental outcome in very-low-birth-weight infants with or without
      periventricular haemorrhage and/or leucomalacia.
AB  - The aim of the study was to verify the predictive value of ultrasound performed
      in the neonatal period for short-term neurodevelopmental prognosis in 122 preterm
      very-low-birth-weight infants followed-up at 36 months. Neuromotor development
      was favourable in 53 (87%) subjects with normal ultrasound findings and in 21
      (81%) subjects presenting uncomplicated haemorrhage. However, sensory and/or
      cognitive sequelae developed in 13% and 19% of the two groups, respectively.
      Outcome was unfavourable in 14 (50%) of 28 patients with ultrasound findings of
      complicated cerebral haemorrhages and in 5 (71%) of those (7) with ultrasound
      findings of parenchymal lesions without haemorrhage. Neonatal ultrasound
      examination seems to be fundamental in predicting neuromotor, but not cognitive,
      outcome in very-low-birth-weight infants.

PMID- 1384828
TI  - Growth and motor performance in preterm children at 8 years of age.
AB  - At 8 years of age 41 preterm and 24 term children were followed up in a long-term
      prospective study of 46 unselected infants born before 35 completed weeks of
      gestation and of 26 term infants. The two groups were comparable in physical
      growth and there was no significant difference between them in motor performance,
      as evaluated with the Test of Motor Impairment. Only minor motor problems were
      found (in 22% of the preterm and 17% of the term group). In the preterm group,
      motor impairment was correlated to birthweight. The preterm children had less
      developed postural control and manifested more compensatory movements during the
      balance tasks than the term children.

PMID- 1384829
TI  - RNA hybridization for Mycoplasma pneumoniae: a new tool for following the
      epidemiological situation.

PMID- 1384830
TI  - Natural killer cell activity against cultured melanoma cells: a dye-reduction
      technique with studies on augmented activity by interferon subtypes.
AB  - We assessed natural killer (NK) cell activity against cultured melanoma cells
      using a novel method, with observations on the comparative effects of interferons
      (IFNs) in NK-stimulating and anti-proliferative assays. Since the tumour cells
      tested were adherent, a semi-automated colorimetric MTT dye reduction assay was
      developed to assess NK activity. The three adherent human melanoma cell lines Sk
      Mel-28, MM418 and MM96 were shown to be suitable targets for determining NK
      activity. Also, these were representative of the range of sensitivities of
      melanoma cells to the anti-proliferative action of type 1 IFNs. The dose
      dependent stimulation of NK activity by type 1 IFNs was confirmed in this
      alternative assay system. IFN-alpha 2b and IFN-beta ser had equivalent
      stimulatory activities, and IFN-alpha 4 proved less effective, as with assays
      using the classical K562 system. Augmented NK cytotoxicity did not correlate with
      anti-proliferative effects of IFN. In anti-proliferative assays, the hierarchy of
      activity is IFN-beta greater than IFN-alpha 2 greater than IFN-alpha 4, whereas,
      in the NK augmentation assay IFN-beta and IFN-alpha 2 were of equivalent
      activity. Interestingly, MM96 was the cell line most resistant to the direct anti
      proliferative action of IFN, yet it was the most susceptible of the melanoma cell
      lines to cytotoxicity by NK cells, whether stimulated or unstimulated by IFN.

PMID- 1384832
TI  - Adjuvant cytostatic therapy of breast cancer as an important factor in the
      postponing of a relapse and longer survival period.
AB  - This prospective clinical study shows the results of the adjuvant cytostatic
      therapy (ACT) in breast cancer applied to patients in the premenopausal age.
      Cyclophosphamide, methotrexate, 5-fluorouracil (CMF) group (70 patients): after
      operative and radiotherapeutic treatment the ACT is applied over the period of
      six months (six cycles). Control group (71 patients): only operative and
      radiotherapeutic treatment. Protocol of the ACT: cyclophosphamide, methotrexate,
      5-fluorouracil (CMF) over 5 days with a 4-week break. Total 6 cycles. Control
      period: 10 years. Stratification of patients was made on the basis of the
      following risk factors: size of the tumour, number of positive lymph nodes of
      ipsilateral axilla, grade of the differentiation of the tumour, hormonal
      dependence of the tumour. Statistical method of analysis: actuary calculation,
      the Hi square test. The results show that the application of the ACT is
      statistically significant (P < 0.05) in regard to the disease-free interval.
      However, concerning the survival, the usefulness of its application is present
      but not statistically significant on the significance level of 5%. The usefulness
      of the ACT application as regards high risk factors (T3, T4 > or = 4 lymph nodes,
      grade of differentiation II, III, ER-PR-) is statistically significant (P < 0.05)
      both in regard to the DFI and survival. Regarding low risk factors the ACT
      application adversely influenced the results in the control group. This is
      probably the result of the ACT toxicity. The patients have a favourable prognosis
      in this subgroup in regard to the staging and biological nature of the tumour.
      The ACT in the premenopausal age of patients with high risk factors gives a
      significantly better results concerning the procrastination of relapse and the
      length of the survival period.

PMID- 1384833
TI  - Photocoagulation of diabetic maculopathy.
AB  - A comparative analysis of the efficiency of the two current techniques of the
      focal photocoagulation: the focal macular perifoveolar and the focal extramacular
      technique in the treatment of diabetic maculopathy was performed. The study
      included 92 insulin non-dependent diabetics with nonproliferative diabetic
      retinopathy, divided into two groups. The assessment of the results has been
      carried out on the basis of the changes in the visual acuity 12 months after the
      argon laser treatment. There has been a statistically significant difference in
      the effects of the focal macular perifoveolar treatment and the focal
      extramacular treatment on the visual acuity. It has been improved for two or more
      lines on the Snellen chart, to which difference has contributed the significantly
      lesser worsening of the visual acuity as a result of the focal macular
      perifoveolar treatment (p < 0.05). The mean visual acuity following the focal
      extramacular treatment has shown a statistically non-significant decrease (p <
      0.05), practically with no change at all, but the mean visual acuity following
      the focal macular perifoveolar treatment has shown a statistically significant
      improvement (p < 0.01). It has been established that the focal macular
      perifoveolar treatment shows better results than the focal extramacular treatment
      in the treatment of diabetic maculopathy. This has been established by checking
      the visual acuity a year after the treatment had been completed. This leads to
      the conclusion that this treatment is preferable in everyday work.

PMID- 1384831
TI  - Protective effect of MDP-Lys(L18), a synthetic derivative of muramyldipeptide, on
      murine cytomegalovirus infection.
AB  - The host-mediated antiviral effect of N alpha-(N-acetylmuramyl-L-alanyl-D
      isoglutaminyl)-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)] was evaluated in mice
      against murine cytomegalovirus (MCMV) infection. Mice treated with 800 micrograms
      of MDP-Lys(L18) on day 2 before the virus challenge survived systemic lethal
      infection. The protective effect of MDP-Lys(L18) was evidenced by an increase in
      plaque-forming units per LD50 and a decrease in virus titers in the target
      organs. No significant difference in the serum interferon level and 2',5'
      oligoadenylate synthetase activity was observed among the mice treated with test
      compounds or phosphate-buffered saline, thought they were higher in MCMV-infected
      mice than in mock-infected mice. The natural killer (NK) activity was augmented
      remarkably in the mice treated with MDP-Lys(L18) or its original component,
      muramyldipeptide (MDP). MDP-Lys(L18) showed neither virocidal nor virostatic
      activity on MCMV in vitro. Thus, MDP-Lys(L18)-induced resistance against MCMV
      infection seems to be host-mediated. The MDP-Lys(L18)-induced resistance was not
      abrogated by the treatment with anti-asialo GM1 serum. The NK activity augmented
      by MDP-Lys(L18) may contribute to some part of the protective effect, though the
      augmentation of the NK activity alone did not correlate completely with the
      protective effect of MDP-Lys(L18). In addition, no difference was observed in
      anti-MCMV activity among peritoneal exudate cells from mice treated with MDP
      Lys(L18), MDP or phosphate-buffered saline. Therefore, another host-mediated
      factor(s) may also participate in the antiviral effect of MDP-Lys(L18).

PMID- 1384834
TI  - The possible role of skin surface lipid in rosacea with epitheloid granulomas.
AB  - The examination was carried out in 50 rosacea patients (30 females and 20 males)
      in order to establish the connexion between skin surface lipids, infestation with
      Demodex folliculorum and previous local corticosteroid treatment with the
      appearance of epitheloid granulomas. Our analysis showed three types of
      histological conditions: 1) chronic dermatitis of the rosacea type was noted in
      15 patients (30%); 2) granulomas composed of epitheloid cells was found in 16
      patients (32%). In three female patients of this group presence of caseous
      necrosis associated with epitheloid granuloma was noted, too; 3) prevalence of
      perifollicular absceses was found in 19 patients (38%). Demodex folliculorum was
      detected in 43 rosacea patients (86%), considerably more then in the control
      group. The normal value of the skin surface lipids was found in 9 female rosacea
      patients (30%) and in 9 female controls (43%), in 8 male rosacea patients (40%)
      and in 5 males controls (33%). Lower amounts of skin surface lipids were found in
      19 female rosacea patients (63%) and in 9 female controls (43%), in 4 male
      rosacea patients (20%) and in 1 male control (7%). Higher amounts of skin surface
      lipids were found in 2 female rosacea patients (7%) and in 3 female controls
      (14%), in 8 male rosacea patients (40%) and in 9 male controls (60%). Lower
      quantities of lipids determined a higher incidence of Demodex folliculorum in
      rosacea patients. Demodex folliculorum were also more frequently detected in
      patients who had previously been treated with topical corticosteroids (even in
      91.9%), what was often followed by epitheloid granulomas. The treatment with
      tetracycline yielded good or excellent results in 90% of all the patients.

PMID- 1384835
TI  - Problems of geriatric pharmacotherapy.
AB  - No one dies of old age by itself; death is always due to a disease of some kind.
      This means that safe and effective therapy for old people is a matter of great
      practical importance. From what has been said above it will be obvious that the
      effects of drugs in old people are similar to their effects in the young, but
      there may be differences in degree in their susceptibility to adverse reactions.
      The existing data are by no means abundant, sometimes contradictory and of
      limited evidential value. Looking at the picture as a whole, one cannot but agree
      with those authors who state that the available results are insufficient to
      substantiate the general opinion that old age in itself heightens the risk of all
      forms of pharmacotherapy. From the practical point of view it is nowadays
      essential that no drug should be prescribed for an elderly patient without strict
      scrutiny of the need for it, that such drugs should not be administered for any
      longer than is absolutely necessary, that treatment should normally be started
      with smaller doses than those usually given to younger adults and, lastly, that
      surveillance for possible side effects should be particularly close. The author
      states that it must not be forgotten that geriatric patients frequently consult
      specialists in addition to their family doctors and that they are perhaps
      overinclined to listen to advice on drug treatment from those about them. One of
      the duties of the family doctor is to check the assortment of drugs which his
      patient is consuming--often an alarming total--and to cut down their number to
      those which are really necessary.

PMID- 1384836
TI  - Coronary vascularization in patient maintained on chronic hemodialysis.
AB  - A patient, maintained on hemodialysis for 16 years because of chronic renal
      failure caused by chronic glomerulonephritis, who underwent surgical coronary
      revascularization, is presented. The authors conclude that preoperative
      hemodialysis, careful hydration of the patient, right management of
      cardiopulmonary bypass, use of hemodilution and aprotinin can contribute to
      escivating of hemofiltration and heterologue blood transfusion in uremic patients
      who undergo well timed coronary revascularization.

PMID- 1384837
TI  - A brief review of Croatian medical history until the 19 century--Part 1.
AB  - The purpose of this study is to remind the contemporary readers of the role and
      contribution of Croatian medical heritage in the development of medicine in
      Europe and the World, as well as of the development of medical concepts and
      medical practice on the territory of what is Croatia today. Selected examples are
      presented of the famous events and notable persons from the ancient time until
      the middle of the 19th century.

PMID- 1384838
TI  - The natural history of mild idiopathic scoliosis.
AB  - The aim of the research was to monitor the natural history of mild idiopathic
      scoliosis in school children, primarily those with a scoliotic curve lesser than
      20 degrees according to Cobb who had been treated by regular observation and
      sports activities. A total of 97 children, 73 girls and 24 boys, aged between 9
      and 14 years were enrolled. All the children were monitored for three years and
      in this period they were subjected to regular examinations and to at least three
      X-ray examinations. There were 51 thoracal, 39 thoracolumbar and 7 lumbar cases
      of scoliosis. After the three year observation period thoracic scoliosis improved
      in 56.9% of patients, 17.7% showed no change while 25.5% of the cases
      deteriorated. Nonprogressive thoracolumbar scoliosis was found in 76.9% of the
      cases, 12.9% showed no change from baseline while in 10.3% curve progression was
      noticed. Nonprogressive lumbar scoliosis was observed in 4 cases, in 2 cases the
      condition was unaltered while in 1 case curve progression was noticed. In the
      whole group there were 18.6% cases of progressive scoliosis. The results of this
      research have confirmed that regular observation and sports activities are the
      best methods of treating idiopathic scoliosis with a curve lesser than 20 degrees
      according to Cobb.

PMID- 1384839
TI  - Morphological cephalometric differences between two European populations.
AB  - Earlier research in craniofacial morphology of the inhabitants of Mainz (Germany)
      and Zagreb (Croatia), who represent the populations of wider areas, have shown
      some roentgen-cephalometric differences. The aim of this study is to determine
      the craniofacial morphologic differences of these populations in three
      dimensions. The sample consists of 200 adult examinees, male and female
      respectively, inhabiting the mentioned areas. The sample has been chosen so that
      the examinees with prominent craniofacial anomalies have been excluded. Twenty
      three craniofacial parameters with the usual anthropometric instruments have been
      measured. The data have been processed by using elementary descriptive statistics
      and discriminant analysis. The results have shown that in Mainz examinees longer
      and narrower heads and higher faces in comparison with Zagreb examinees,
      predominate. Significant differences in forehead widths and bipupilar distances
      have been found.

PMID- 1384840
TI  - Changes in coagulability of blood in patients with cerebrovascular disease in
      various meteorological situations.
AB  - The authors are dealing with the influence of meteorological factors on vascular
      diseases, primarily on patients with cerebro-vascular disturbances. The
      parameters mentioned in some studies are also presented in the introduction.
      There are still few studies by means of which it can be enlightened what happens
      in the human body affected by atmospheric disturbances. Therefore the basic
      intention of this study was to come up with answers to at least some segments of
      this complex problem. A group of patients with cerebrovascular symptoms and signs
      was chosen for examination. Tests were carried out during cold and warm front
      passages in anticyclonal situations and low gradient pressure fields within 47
      days. In the first stage the tests were carried out only in one day and later for
      three consecutive days. Meteorological reports are given too. As for medical
      parameters, the following were controlled: the neurology status, blood pressure,
      blood test, ECG, REG. The coagulum was regularly checked. The examination was
      carried out in 12 male and 14 female patients, the age range 43-78. On the basis
      of the tests, the authors concluded that the most significant changes were
      noticed in the coagulum and thromboelastogram. According to the results, these
      changes are manifested during the cold front and during the cold spell caused by
      it. The findings point to a significant increasing of the thrombocyte aggregation
      and partly the aggregation index, which can be clinically manifested as the
      patient's health aggravation. Although other parameters of coagulation did not
      show significant changes, it cannot be deduced whether they are susceptible to
      the circumstances in the atmosphere or not.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384841
TI  - An approximation of stenotic aortic valve area by phonomechanocardiographic
      method: the comparative study of noninvasive methods.
AB  - Phonomechanocardiographic and ultrasonocardiographic parameters were compared in
      the multiplex manner in order to assess a degree of narrowing of the stenotic
      aortic valve areas. Adult patients with aortic valve stenosis were included in
      the study. The main condition for admission in the research sample was that the
      mean rate of circumferential fibre shortening be greater than 1 s-1 i.e.
      "compensated" preejection period/ejection time ratio (PEP/LVET). The control
      group were persons as sample stratified from healthy population. A possibility of
      approximate assessment of valve areas in patients with aortic stenosis is
      rendered by inserting the phonomechanocardiographic parameters in the modified
      Gorlin and Gorlin formula, provided that values of the normalised ejection
      function index (PEP/LVET2) and the ejection-isovolumetric coefficient corrected
      for pulse transmission time (LVET/IVCT+PTT) are known. The
      phonomechanocardiographic indexes of the transvalvular aortic pressure gradient
      and normalised stroke volume correlate curvilinear. The value of the LVET/IVCT +
      PTT equal or greater than that extrapolated for the given PEP/LVET2 in our
      formula means critically stenotic aortic valve area below 0.8 cm2. The given
      approximation could be used as a noninvasive and nongeometric polycardiographic
      or phonomechanocardiographic pattern for assessing the degree of narrowing of
      aortic valve area. The aortic valve stenosis is an illness in which a lot is
      expected from noninvasive cardiologic parameters when a surgical indication is in
      question. A severe or tight aortic valve stenosis, which required a surgical
      treatment according to current views, existed when valve area is less than 0.8
      cm2 or when the transvalvular aortic systolic pressure gradient is greater than
      50 mm Hg or 6.67 kPa, but with normal cardiac index in the same time.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1384842
TI  - Viral RNA-dependent DNA polymerase. 1970.

PMID- 1384843
TI  - High-efficiency gene transfer into mammalian cells: generation of helper-free
      recombinant retrovirus with broad mammalian host range. 1984.

PMID- 1384844
TI  - RNA-dependent DNA polymerase in virions of Rous sarcoma virus. 1970.

PMID- 1384845
TI  - [The effect of 6% HES 200/0.6-0.66 on plasma volume and blood coagulation].
AB  - The main goal of the recent study was to evaluate changes in plasma volume due to
      the application of 6% HES 200/0.6-0.66. 12 patients according to the ASA physical
      status classification (I, II) undergoing minor surgical interventions received
      500 ml of this artificial plasma substitute within 30 min. In a control group (n
      = 12), 500 ml of lactated Ringer's solution was given within the same period. A
      further question of the present investigation was the possible influence of 6%
      HES on coagulation during the following period (1st-3rd postoperative days). 6%
      HES 200/0.6-0.66 led to an additional augmentation of plasma volume measured via
      the mechanical oscillator technique of 200 ml (40% of the volume given)
      immediately at the end of infusion. A second increase in plasma volume of 100 ml
      (20% of the volume infused) could be observed 1 h later. With exception of the
      activity of factor VIII, the coagulation parameters had not been altered by
      infusion of 6% HES. The activity of factor VIII decreased to about 50% of the
      control level but showed a tendency to normalization within the following
      observation period. 6% HES 200/0.6-0.66 has a marked volume-expanding effect and
      exerts no influence on coagulation except a temporary decrease of factor VIII
      activity.

PMID- 1384846
TI  - [L. Heilmann, E. Lorch, B. Hojnacki, H. Muntefering, H. Forster: Storage of two
      different hydroxyethyl starch preparations in the placenta after hemodilution in
      intrauterine growth retardation or hypertension in pregnancy].

PMID- 1384847
TI  - Incorporation of radiophosphorus from labeled oligodeoxynucleotides into RNA of
      mycoplasma in cell cultures.
AB  - We have found that various mycoplasma species quickly and efficiently incorporate
      radiophosphorus into their RNA from labeled oligonucleotides added to the medium.
      The label can be in any of several positions in an oligodeoxynucleotide, and
      incorporation also occurs efficiently from labeled RNA. Mycoplasmas also
      incorporate the radiolabel when they infect a mammalian cell culture; the host
      cells do not. This incorporation presumably involves uptake of the
      oligodeoxynucleotide followed by digestion to mononucleotides, conversion to
      ribonucleotides, and incorporation in new RNA. We believe that the processing of
      oligodeoxynucleotides by mycoplasma could be a source of artifacts in antisense
      work in cell culture and could have implications for the development of antisense
      therapeutics. We also suggest ways to exploit the incorporation phenomenon in
      mycoplasma testing.

PMID- 1384848
TI  - Configuration, in serial reconstruction, of individual axons projecting from area
      V2 to V4 in the macaque monkey.
AB  - The detailed morphology of long extrinsically projecting axons in the neocortex
      has been difficult to investigate and is in fact poorly understood. Some data,
      based on extracellular injections of Phaseolus vulgaris leucoagglutinin (PHA-L),
      are available for individual axons projecting from area V1 to area V2 or MT. Like
      geniculocortical projections, axons projecting from area V1 to area MT are
      readily identifiable (they typically have a bistratified termination pattern and
      large terminal specializations and are of large caliber), but those projecting
      from area V1 to V2 are more variable. To provide a broader basis for interpreting
      constant and variable features of axon morphology, we used high-resolution serial
      section reconstruction to analyze small populations of PHA-L-labeled axons
      projecting from area V2 to V4. Reconstruction of 20 axons suggests that this
      system is variable in terms of overall configuration and laminar distribution.
      Most terminal arbors are located at the border between layers 3 and 4, but some
      remain entirely within layer 3 or 4, some target preferentially the superficial
      layers (1, 2, and 3A), and some have collaterals in layer 5 or, rarely, layer 6.
      Arbor size is fairly constant among the three visual cortical projections
      examined so far (typically about 200 microns in diameter). In area V4, however,
      axons frequently have three or four separate arbors, which branch divergently (in
      one instance, over 2.6 mm x 3.0 mm). These features may be correlated with
      aspects of the particular functional organization of area V4, such as coarse
      topography, large receptive field size, and modularity. Axonal variability may
      also denote differences, morphological or physiological, among neurons of origin
      in area V2.

PMID- 1384849
TI  - Motors for fast axonal transport.
AB  - In neurons and other animal cells, membrane-bound vesicles course rapidly along
      cytoskeletal filaments to reach their destinations. Based on a variety of in vivo
      studies it is becoming clear that the microtubule-based motor, kinesin (and its
      relatives), drive vesicle movements in axons. Surprisingly, some axonal membranes
      have the capacity to move on both microtubules and actin filaments.

PMID- 1384850
TI  - Identification of solvent-exposed regions of an FK-506 analog, ascomycin, bound
      to FKBP using a paramagnetic probe.
AB  - The solvent-exposed regions of (U-13C)ascomycin when bound to its putative target
      protein, FKBP, have been identified based on the different proton longitudinal
      relaxation rates (R1 = 1/T1) measured in the absence and presence of the
      paramagnetic relaxation reagent, 4-hydroxy-2,2,6,6-tetramethyl-piperidinyl-1-oxy
      (HyTEMPO). The proton T1S of bound ascomycin were determined using a pulse
      sequence (T1-HMQC) which consists of a 180 degree proton pulse and a variable
      delay (tau) followed by a heteronuclear multiple quantum correlation (HMQC)
      experiment. The solvent-exposed regions of ascomycin determined by these
      experiments are compared to NOE data in which ascomycin/FKBP contacts were
      identified and to the X-ray structure of the FK-506/FKBP complex.

PMID- 1384851
TI  - NMR spectroscopy of hydroxyl protons in aqueous solutions of peptides and
      proteins.
AB  - Hydroxyl groups of serine and threonine, and to some extent also tyrosine are
      usually located on or near the surface of proteins. NMR observations of the
      hydroxyl protons is therefore of interest to support investigations of the
      protein surface in solution, and knowledge of the hydroxyl NMR lines is
      indispensable as a reference for studies of protein hydration in solution. In
      this paper, solvent suppression schemes recently developed for observation of
      hydration water resonances were used to observe hydroxyl protons of serine,
      threonine and tyrosine in aqueous solutions of small model peptides and the
      protein basic pancreatic trypsin inhibitor (BPTI). The chemical shifts of the
      hydroxyl protons of serine and threonine were found to be between 5.4 and 6.2
      ppm, with random-coil shifts at 4 degrees C of 5.92 ppm and 5.88 ppm,
      respectively, and those of tyrosine between 9.6 and 10.1 ppm, with a random-coil
      shift of 9.78 ppm. Since these spectral regions are virtually free of other
      polypeptide 1H NMR signals, cross peaks with the hydroxyl protons are usually
      well separated even in homonuclear two-dimensional 1H NMR spectra. To illustrate
      the practical use of hydroxyl proton NMR in polypeptides, the conformations of
      the side-chain hydroxyl groups in BPTI were characterized by measurements of
      nuclear Overhauser effects and scalar coupling constants involving the hydroxyl
      protons. In addition, hydroxyl proton exchange rates were measured as a function
      of pH, where simple first-order rate processes were observed for both acid- and
      base-catalysed exchange of all but one of the hydroxyl-bearing residues in BPTI.
      For the conformations of the individual Ser, Thr and Tyr side chains
      characterized in the solution structure with the use of hydroxyl proton NMR, both
      exact coincidence and significant differences relative to the corresponding BPTI
      crystal structure data were observed.

PMID- 1384853
TI  - Effects of elevated zinc intake on the copper metabolism and the pancreas of the
      mouse.
AB  - The effects of moderately elevated zinc (Zn) intake on copper (Cu) metabolism and
      on the pancreas were studied. Zn (80 mg/L) as acetate was added to the drinking
      water of male Swiss mice for up to 12 weeks, which increased the total daily Zn
      intake to about 5 times the adequate level. Total Cu and Zn in tissues was
      measured by atomic absorption spectrometry. 64Cu was used to measure some effects
      of the Zn suppletion on the Cu metabolism. Furthermore, ceruloplasmin and amylase
      in plasma and superoxide dismutase in erythrocytes were measured. The pancreas
      was examined by light microscopy. The Zn supplementation decreased the 64Cu
      absorption and increased the retention of 64Cu, but did not lead to a Cu
      deficiency. Microscopic examination of the pancreas revealed focal hypertrophy of
      acinar cells, occasionally accompanied by vacuolation of cytoplasm and/or the
      presence of degenerated cells. The results, obtained in mice given a moderately
      increased Zn intake, should be interpreted as a warning against the chronic use
      in man of high doses of Zn for non-medical purposes.

PMID- 1384852
TI  - Reduction of CSF monoamine metabolites in poststroke depression: a preliminary
      report.
AB  - Monoamine metabolites were measured in the cerebrospinal fluid (CSF) of depressed
      and nondepressed patients with acute stroke lesions and in nondepressed patients
      without stroke lesions. Depressed stroke patients had a significantly lower
      concentration of CSF 5-hydroxyindoleacetic acid (5-HIAA; a serotonin metabolite)
      than the other two groups. These findings suggest that poststroke depression may
      be mediated by serotonergic mechanisms.

PMID- 1384854
TI  - Role of interferons in the therapy of melanoma.
AB  - The increased incidence of disease, the relative unresponsiveness of advanced
      tumour to conventional therapies, and high socioeconomic costs make the malignant
      melanoma an aggressive cancer. During the last decade, several new biological
      agents have been developed, some of which have shown significant activity in the
      treatment of disease. However, the impact on the management of melanoma patients
      is still far from being conclusive. Among biological response modifiers (BRMs),
      interferons (IFNs) have generated a great deal of interest and have been
      extensively employed, although incorrectly. IFNs have been used without a
      specific rationale and at antiproliferative rather than biologically active
      doses; no extensive laboratory monitoring has been performed. In this paper data
      available in the current literature are reviewed and the efficacies of the
      different IFNs, used alone or in combination and in various treatment regimens,
      are compared in order to understand what is the place of IFNs in the management
      of patients with metastatic melanoma. Results are encouraging but still
      disappointing with the most effective treatment, with an overall response rate of
      28.5% (10.5% complete responses). However, these results need confirmation. In
      conclusion, IFN is effective in the therapy of advanced melanoma, but improved
      response rates are necessary before it may be suitable for general, rather than
      investigative, use. Alternative biotherapeutical approaches and strategies are
      suggested.

PMID- 1384855
TI  - Reversible depigmentation of human melanoma cells by halistanol trisulphate, a
      novel marine sterol.
AB  - The pigmented human melanoma cell line, MM418, became demelanized when treated
      continuously with a nontoxic level of halistanol trisulphate (HTS), a C29
      steroidal detergent isolated from a marine sponge. Nontoxic levels of halistanol
      or of a range of anionic, cationic and neutral detergents had no such effect.
      Control MM418 cells varied greatly in size, appearance and pigmentation; HTS
      treated cells were smaller than controls, had a uniform, generally bipolar
      appearance, and lacked pigment. HTS induced only minor changes in cell
      ultrastructure, with fewer mature melanosomes being found in treated cells.
      Suppression of melanin synthesis was apparent within 24 h of addition of HTS, as
      judged by inhibited incorporation of the false precursor, 5[125I]-2-thiouracil.
      Reversal of inhibition occurred within the same period after removal of HTS.
      Tyrosinase activity gradually decreased to 25% of the control value during a 19
      day treatment with HTS, and expression of two carbohydrate-dependent tyrosinase
      epitopes, 5C12 and 2B7, was abolished. Expression of one other melanosomal
      protein and of vimentin was not affected. The results suggest that HTS inhibits
      maturation of tyrosinase to a form associated with melanin synthesis.

PMID- 1384856
TI  - On the engineering of rDNA proteins for purification by immobilized metal
      affinity chromatography: applications to alternating histidine-containing
      chimeric proteins from recombinant Escherichia coli.
AB  - Recently we reported (D. B. Evans, W. G. Tarpley, and S. K. Sharma, 1991, Protein
      Expression Purif. 2, 205-213) the cloning, expression, and characterization of
      recombinant chimeric proteins with an N-terminal metal-binding peptide (mbp), His
      Asp-His-Asp-His, and a renin cleavage site. Using these chimerics as examples, we
      describe here the use of genetically engineered alternating histidines in the
      purification of these chimerics by immobilized metal affinity chromatography
      (IMAC). In these chimerics, an alternate histidine-containing peptide was fused
      to the N-termini of HIV reverse transcriptase (HIV RT) and beta-galactosidase.
      These chimerics were retarded on immobilized nickel very strongly and could be
      completely eluted only by the use of 100 mM imidazole, whereas the wildtype HIV
      RT and Escherichia coli contaminating proteins were eluted between 10 and 35 mM
      imidazole. When the DNA coding for the mbp was removed, the resulting chimerics
      were recovered from the IMAC column at 35 mM imidazole. The strong and specific
      interaction between the chimeric protein and the immobilized metal ion was also
      abolished when the mbp was specifically cleaved by human renin. It is concluded
      from these studies that tailoring recombinant proteins with three or more
      alternate histidines should result in the isolation of such chimeric proteins
      from crude mixtures in a single step. Since IMAC is amendable to scale up, the
      tailored specificity engineered into the protein of interest via an mbp should
      allow one to achieve large-scale isolation of recombinant proteins from bacterial
      and nonbacterial hosts in a highly predictable manner.

PMID- 1384857
TI  - Purification of recombinant antigenic epitopes of the human 68-kDa (U1)
      ribonucleoprotein antigen using the expression system pH6EX3 followed by metal
      chelating affinity chromatography.
AB  - A novel plasmid expression vector (pH6EX3) that directs the synthesis of a fusion
      protein with a histidine hexapeptide at its N-terminus and a foreign protein at
      its C-terminus was constructed. The fusion gene is controlled by a strong tac
      promoter, leading to high-level expression of recombinant protein in several
      bacterial strains; the protein is deposited mainly as an insoluble mass in
      inclusion bodies. The fusion protein can be purified from the insoluble cell
      fraction by one-step affinity chromatography based on the selective interaction
      between the histidine hexapeptide and a metal chelating matrix charged with Ni2+
      ions. The principle of this new system was tested by expressing and purifying
      antigenic epitopes of the human 68-kDa (U1) ribonucleoprotein autoantigen. With
      the use of column chromatography and pH gradient elution, about 25 micrograms
      recombinant protein/ml of bacterial culture was obtained.

PMID- 1384858
TI  - Higher specific activity of the Escherichia coli glutamyl-tRNA synthetase
      purified to homogeneity by a six-hour procedure.
AB  - The glutamyl-tRNA synthetase (EC 6.1.1.17) of Escherichia coli was purified to
      homogeneity from the overproducing strain DH5 alpha(pLQ7612) by a two-step
      procedure that takes only about 6 h and yields 10 mg of enzyme per gram of wet
      cells. The process consists of a two-phase polyethylene glycol-dextran partition,
      the top phase of which is diluted and directly applied to an anion-exchange FPLC
      MonoQ column. The purified enzyme has a specific activity about twice that of the
      same enzyme purified to homogeneity by the lengthy conventional procedure from
      either a normal strain or this overproducing strain. This difference is discussed
      in relation to the generation of microheterogeneity in proteins during their
      purification.

PMID- 1384859
TI  - Resolution of microheterogeneity associated with recombinant HIV-1 heterodimeric
      reverse transcriptase.
AB  - HIV-1 reverse transcriptase (RT) has been successfully expressed as a
      biologically active recombinant protein in Escherichia coli and purified to
      homogeneity. After partial purification, RT was obtained primarily in a
      heterodimeric form represented by two subunits of 66 and 51 kDa, but the
      preparation also included several forms distinguishable in size and charge by
      chromatography on ionic-exchange and gel-filtration columns. We have developed a
      purification method that yields a single heterodimeric form of RT. Our strategy
      involves the selection of RT molecules exhibiting uniformity in elution from QAE
      Sepharose anion-exchange columns and Superose 12 gel-filtration columns. In the
      former, RT is resolved into multiple peaks on the basis of enzymatic activity,
      one of which represents highly active and pure p66:p51 heterodimeric RT. This
      highly active RT fraction, after gel-filtration chromatography, yields a
      compositionally pure protein product free of observable microheterogeneity by 1D
      and 2D polyacrylamide gel electrophoresis under a variety of conditions.
      Furthermore, the RNAse H enzymatic activity associated with HIV-1 RT has been
      demonstrated to coelute with the purified polymerase activity during gel
      filtration at a size (120 kDa) consistent with its location on the heterodimeric
      protein molecule.

PMID- 1384860
TI  - Comparative analysis of native and cysteine-deficient HIV-1 reverse
      transcriptase.
AB  - To study the subunit structure and the active site of human immunodeficiency
      virus reverse transcriptase (RT), the enzyme was expressed in E. coli and
      purified to homogeneity in large quantities. The recombinant enzyme consists of
      two major polypeptides of 66,000 and 53,000 Da in equimolar amounts and a minor
      species of 51,000 Da. Amino acid sequence analysis of the recombinant proteins
      revealed that the amino termini of the two major subunits are identical to that
      of the virion-derived enzyme. The two cysteinyl residues at positions 38 and 280
      in the RT amino acid sequence were replaced by alanine in an attempt to elucidate
      the role of the sulfhydryl groups in RT enzyme activities, heterodimer formation,
      and intrasubunit linkage. The results reported here show that the two cysteinyls
      are dispensable and their absence in the amino acid sequence of the reverse
      transcriptase does not affect DNA polymerase or ribonuclease H enzyme activities
      or the formation of heterodimer structures. Furthermore, inhibitors of polymerase
      activity such as 3-azidothymidine triphosphate, dideoxythymidine triphosphate,
      and tetrahydroimidazo[4,5,1-JK][1,4]benzodiazepens (1H)-one are equally effective
      on the mutant containing no cysteinyl residues and the wild-type enzyme.

PMID- 1384861
TI  - T cells and human autoimmune thyroid disease: emerging data show lack of need to
      invoke suppressor T cell problems.
AB  - Human T cells recognize self and foreign antigens when such antigens are
      processed into small peptides and bound to molecules coded for by genes of the
      HLA region on chromosome 6. The part of the T-cell surface which is responsible
      for such recognition is a set of molecules coded for by a variety of genes and
      known as the T-cell-receptor complex. In animal models, T cells are able to
      transfer autoimmune thyroiditis and T cells have, therefore, long been implicated
      in the etiology of human autoimmune thyroid disease (AITD). Information gained
      from the study of intrathyroidal T cells and thyroid antigen-specific T-cell
      clones has shown that in patients with Graves' disease, mainly helper T-cell
      clones have been obtained, whereas in autoimmune (Hashimoto's) thyroiditis
      cytolytic T-cell clones may be predominant. Such thyroid antigen-specific T cells
      have now been shown to recognize one or other of the three major thyroid-specific
      antigens; thyroglobulin, thyroid peroxidase, or the TSH receptor and efforts are
      currently in progress to characterize the T-cell epitopes of these major thyroid
      autoantigens. Recent findings of restricted T-cell receptor V gene use amongst
      intrathyroidal T cells confirm the primary role of T cells in human thyroid
      autoimmune processes leading to AITD. However, the mechanisms whereby such
      autoreactive T cells escape deletion and anergy, and how they become activated,
      remain uncertain. There is compelling evidence that the thyroid cell itself, by
      expressing HLA molecules, and presenting antigen directly to the T cells, may
      initiate disease, perhaps after an external insult.

PMID- 1384862
TI  - The effects of FK-506 and cyclosporin A on the proliferation of PHA-stimulated T
      cells in response to IL-2, IL-4 or IL-6.
AB  - Stimulated by PHA, the T cells responded well to exogenous IL-2, IL-4 or IL-6,
      but the responses were inhibited by FK-506 or cyclosporin A (Cs A). In contrast,
      when stimulated by PMA, the T cells responded to IL-2 and IL-4, but not to IL-6
      and the responses were not inhibited by FK-506 and Cs A. Kinetic studies showed
      that FK-506 and Cs A had no inhibitory effects on T cell proliferation in
      response to IL-2 and IL-4 after the resting T cells were pulsed with PHA alone
      for a certain time. However, the response of the PHA-pulsed T cells to IL-6 was
      still inhibited by FK-506 or Cs A, but the inhibitory effect gradually decreased
      as the time in which the PHA-pulsed T cells interacted with IL-6 was prolonged.
      In a control system, the proliferation of the T cells that were treated with FK
      506 or Cs A for 3 h and washed 3 times was not inhibited when the T cells were
      stimulated with PHA in combination with either IL-2, IL-4 or IL-6. Our data
      suggest that FK-506 and Cs A interfere with the early steps of T cell
      proliferation after stimulation of PHA, but not PMA. It is likely that the two
      drugs inhibit the expression of lymphokine receptors, by interfering Ca(2+)
      related signals and that IL-6 induces T cell proliferation in a different way
      than IL-2 and IL-4, which are FK-506- and Cs A-sensitive.

PMID- 1384863
TI  - Effects of anti-CD11a, anti-CD11b and anti-CD18 on histamine release from human
      basophils primed with IL-3.
AB  - This study was carried out to investigate the possible role of adhesion molecules
      in the histamine release from human basophils primed with recombinant IL-3 (rIL
      3). Anti-IgE monoclonal antibody (0.1 microgram/ml) did not induce apparent
      histamine release by itself, however, remarkable histamine release was induced
      from rIL-3-primed human basophils triggered by anti-IgE. Bear-1 (anti-CD11b
      monoclonal antibody) inhibited the histamine release enhanced by rIL-3, however
      SPV-L7 (anti-CD11a monoclonal antibody) or CLB-LFA1/1 (anti-CD18 monoclonal
      antibody) did not inhibit the histamine release enhanced by rIL-3 at all. The
      present study suggests that alpha-chain of Mac-1 is involved in the priming
      effect of IL-3 to increase histamine release from human basophils.

PMID- 1384864
TI  - Mast cell response to formaldehyde. 1. Modulation of mediator release.
AB  - To examine the effects of the atmospheric pollutant formaldehyde on functionally
      distinct mast cells, peritoneal mast cells (PMC), intestinal mucosal mast cells
      (IMMC) and mouse bone-marrow-derived mast cells (BMMC) were incubated with
      various concentrations of formaldehyde. Pretreatment for 30 min with up to 100
      micrograms/ml formaldehyde was not cytotoxic to mast cells. Formaldehyde (1-10
      micrograms/ml) alone induced low levels of histamine release (< 10%) from IMMC
      and BMMC. Antigen-induced histamine release was significantly increased in both
      PMC pretreated with low concentrations of formaldehyde (5-20 micrograms/ml) and
      BMMC pretreated with 10 micrograms/ml formaldehyde but decreased in PMC
      pretreated with a higher concentration (100 micrograms/ml) of formaldehyde. By
      contrast, antigen-induced histamine release was decreased in IMMC pretreated with
      formaldehyde in a dose-dependent manner. Histamine release stimulated with A23187
      was also increased in PMC pretreated with a low concentration (10 micrograms/ml)
      of formaldehyde but decreased in those pretreated with a higher concentration
      (100 micrograms/ml) of formaldehyde. Pretreatment with 10 micrograms/ml
      formaldehyde significantly enhanced beta-hexosaminidase release from PMC
      stimulated with antigen or A23187. Compared to sham-treated PMC, PMC pretreated
      with formaldehyde expressed a markedly depressed natural cytotoxicity for the
      tumor target WEHI-164 (an assay of tumor necrosis factor alpha activity). These
      results suggest that formaldehyde modifies various mast cell functions through
      alterations in cellular metabolism. Such effects may be important in respiratory
      and other diseases associated with formaldehyde exposure.

PMID- 1384865
TI  - Mast cell response to formaldehyde. 2. Induction of stress-like proteins.
AB  - Previously we established that immediately after pretreatment with low
      concentrations (5-10 micrograms/ml) of formaldehyde antigen- and ionophore
      induced histamine secretion was enhanced from peritoneal mast cells (PMC)
      isolated from rats infected with Nippostrongylus brasiliensis. In contrast to
      immediately following pretreatment with low concentrations of formaldehyde, 3 h
      after a 30-min treatment with formaldehyde (10, 50 and 100 micrograms/ml) antigen
      induced histamine secretion from PMC was significantly depressed, and 35S
      methionine incorporation was also decreased. To further explore the effects of
      formaldehyde on mast cells, we investigated protein biosynthesis of PMC following
      formaldehyde treatment and compared this with the effects of hydrogen peroxide
      (H2O2) or heat treatment. One- and two-dimensional SDS-PAGE were used to assess
      the effects. Formaldehyde treatment induced the synthesis of 70- and 72-kD stress
      like proteins in rat PMC. Pretreatment of PMC with 50 microM H2O2 and heat (45
      degrees C) also induced proteins with the same molecular weight. Two-dimensional
      SDS-PAGE analysis established that formaldehyde-induced 70-kD proteins had the
      same pI values as 70-kD heat shock proteins previously observed in mammalian
      cells. These results suggest that formaldehyde, H2O2 and heat shock induce stress
      proteins in rat PMC. It will be important to establish whether or not these
      stress proteins are responsible for the functional alterations observed in the
      mast cells.

PMID- 1384867
TI  - Pharmacological studies on the role of protein kinase C in signal transduction of
      human basophils.
AB  - Recent investigations have demonstrated that activation of basophils involves the
      activation of protein kinase C (PKC). In the present study the effects of
      different nonselective and selective PKC inhibitors on IgE-mediated histamine
      release from human basophils were investigated. While potent but nonselective
      inhibitors such as staurosporine exerted a dose-dependent inhibition of Fc
      epsilon-receptor-mediated histamine release, staurosporine derivatives with high
      selectivity for PKC potentiated the IgE-mediated response. The results provide
      evidence that the histamine release-inhibiting activity of protein kinase
      inhibitors is inversely correlated with their specificity for PKC. This may
      confirm the hypothesis that PKC exerts a negative modulatory role during the
      process of stimulus secretion-coupling following receptor aggregation in
      basophils. Moreover, investigations with phorbol esters and diacylglycerol
      derivatives as potent PKC activators show that direct cellular PKC activation and
      antigen-stimulated mediator release are not closely correlated.

PMID- 1384866
TI  - Differential increase in 12-HETE release and CD29/CD49f expression of platelets
      from normal donors and from patients with atopic dermatitis by Staphylococcus
      aureus.
AB  - The generation of the arachidonic acid-derived inflammatory mediator 12
      hydroeicosatetraenoic acid (HETE) and the expression of CD29 as well as CD49f
      from unstimulated and stimulated platelets has been studied in patients with
      atopic dermatitis (AD) as well as in healthy volunteers. Heat-killed clinical
      isolates of Staphylococcus aureus served as stimuli. Unstimulated platelets from
      patients with AD produced higher amounts of 12-HETE compared to platelets from
      normal donors. The absolute 12-HETE release from platelets of patients with AD
      was significantly higher compared to the control group after stimulation with
      heat-killed S. aureus, whereas the relative increase remained. The expression of
      CD29 and CD49f on unstimulated platelets of patients with AD was markedly
      enhanced compared to platelets from normal donors. Stimulation with S. aureus led
      to similar results as to the CD29 expression on normal and atopic platelets or to
      a markedly higher expression of CD49f on platelets from normal donors. As
      compared to platelets from normal donors the CD49f expression on atopic platelets
      was slightly enhanced by S. aureus. Our data emphasize that platelets may play an
      important role in the pathogenesis of AD by an increased preactivation and by an
      enhanced responsiveness to S. aureus which colonizes permanently the skin of
      patients with AD.

PMID- 1384868
TI  - Epitope analysis of aztreonam by antiaztreonam monoclonal antibodies and possible
      consequences in beta-lactams hypersensitivity.
AB  - Three cell lines producing monoclonal antibodies, Az-1 (IgG1), Az-2 (IgG1) and Az
      3 (IgM) against aztreonam were established. The epitopes and the cross-reactions
      of the antibodies with various beta-lactams, which were conjugated with human
      serum albumin (HSA), were examined by enzyme-linked immunosorbent assay (ELISA)
      and ELISA inhibition test. In ELISA, Az-1 and Az-2 reacted only with aztreonam
      and ceftazidime, which have the same acyl side chain. Furthermore, Az-2 showed a
      strong cross-reaction with carumonam. In the ELISA inhibition test, Az-1 and Az-2
      were inhibited from binding to aztreonam-HSA by aztreonam, ceftazidime, aztreonam
      hydrolysate, aztreonam-epsilon-amino-n-caproic acid (EACA) and ceftazidime-EACA.
      Az-2 was also inhibited with carumonam. From the above results, it seems that Az
      1 can recognize only the degraded structure of monobactam nucleus, and Az-2 can
      recognize the degraded nucleus moiety and the acyl side chain. On the other hand,
      Az-3 displayed broad cross-reaction to various beta-lactams in ELISA.
      Furthermore, the MAb showed no inhibitory reaction with various beta-lactams
      except aztreonam- and ceftazidime-EACA conjugates in the ELISA inhibition test,
      suggesting that Az-3 recognize a new antigenic determinant (NAD), which is formed
      by the conjugation of beta-lactam and carrier protein. The above results indicate
      that antibodies can recognize at least three epitopes of the degraded product(s)
      of aztreonam nucleus, acyl side chain and NAD in aztreonam-protein conjugate.

PMID- 1384869
TI  - Estradiol augments while tamoxifen inhibits rat mast cell secretion.
AB  - Mast cells have been studied extensively for their involvement in allergic
      reactions, where they secrete numerous powerful mediators in response to
      immunoglobulin E and specific antigens. However, they are also triggered by
      neuropeptides, they have been found in close contact with neurons, and they are
      activated in diseases such as angioedema, interstitial cystitis and irritable
      bowel disease, the prevalence of which is much higher in women. When tested on
      purified rat peritoneal mast cells, 17 beta-estradiol augmented secretion of
      histamine and serotonin, starting at 1 microM and in a dose-dependent manner,
      whether stimulated by the mast cell secretagogue compound 48/80 or the
      neuropeptide substance P. However, 17 beta-estradiol did not augment mast cell
      secretion stimulated by immunoglobulin E and specific antiserum indicating that
      immunologic stimulation is under different regulation. Testosterone inhibited
      secretion induced by compound 48/80. Tamoxifen, an estrogen receptor antagonist
      used in the treatment of breast cancer, inhibited serotonin and histamine release
      from purified rat peritoneal mast cells triggered by compound 48/80 or substance
      P. Tamoxifen also inhibited the increase in intracellular free Ca2+ originating
      from an influx of extracellular Ca2+ in response to compound 48/80. Moreover,
      tamoxifen antagonized the synergistic effect of phorbol myristate and the cation
      ionophore A23187 on mast cell secretion, suggesting that tamoxifen's inhibition
      may be due to regulation of protein kinase C activity. Tamoxifen may, therefore,
      have a beneficial effect in other neuroimmunoendocrine disorders both through
      estrogen receptor blockade and inhibition of mast cell secretion.

PMID- 1384870
TI  - [Genetic monitoring of human population exposed to chemical and radiation
      hazards].
AB  - It is impossible to protect human heredity from the ecological consequences of
      environmental pollution if there is no permanent control of hereditary
      variability in human populations, i.e. genetic monitoring. One of the urgent
      problems in genetic monitoring planning is the magnitude of representative
      samples necessary for establishing the significant mutation effect of
      environmental factors. The elevation of the mutation frequency can be determined
      either by the dynamics of the frequencies of hereditary pathology or by
      comparison of the frequencies in populations that differ in harmful factor
      exposures. Comparison of the effects evaluated by cytogenetic, epidemiological
      (registration of congenital malformation frequencies) and molecular-genetic
      methods in various population groups will make it possible to solve the problem
      of safety in the investigated regions.

PMID- 1384871
TI  - [Prenatal diagnosis as a method of prevention of congenital and hereditary
      diseases].
AB  - The program of the prevention of congenital and hereditary diseases with the aid
      of prenatal diagnosis includes a complex of different methods: ultrasonography,
      invasive procedures made at different times of pregnancy, obstetrical monitoring,
      immunochemical blood tests, fetal cytogenetic analysis, pathological, anatomical,
      and syndromological studies in abortuses. Emphasis is laid on the use of the data
      on ultrasound screening of the pregnant and screening of the mother's blood for
      some factors that form a group of women at a greater genetic risk, who require
      prenatal diagnosis. The efficacy of the preventive measures can be enhanced with
      combined use of instrumental, obstetrical and laboratory research methods. The
      establishment of the correct and early diagnosis may, on the one hand, remove the
      tension and concern in the family; on the other hand, it may prevent bearing a
      sick child and provide the married couple with a based genetic counselling about
      progeny.

PMID- 1384872
TI  - [A program of prevention of hereditary lysosomal diseases in the USSR].
AB  - The organization of genetic counselling for the families of patients with
      lysosomal storage diseases (LSD) was based on the interaction of the genetic
      counselling units of this country with a laboratory of inherited metabolic
      diseases of the National Research Center of Medical Genetics, USSR AMS. All the
      patients from 705 families at risk were examined using biochemical techniques and
      methods of somatic cell genetics. In total the loci differentiation was performed
      for 309 patients with mucopolysaccharidoses, glycoproteinoses, mucolipidoses,
      sphingolipidoses and other LSD. 53 families at risk (of 277) were prenatally
      diagnosed. 66 fetuses were diagnosed for mucopolysaccharidoses, type I, II, III,
      A and B, VI, Tay-Sachs disease, Sandhoff's disease, GM1-gangliosidosis,
      metachromatic leukodystrophy, mannosidosis, and multiple sulfatidosis. In total
      18 affected fetuses were diagnosed and aborted. All the prenatal diagnoses were
      verified. The prevalence of mucopolysaccharidoses in two Central Asian republics
      was evaluated as 1:15,000. An Uneven ethnic distribution of different
      mucopolysaccharides in the USSR has also been shown.

PMID- 1384873
TI  - [Computerized analysis in the study of multiple congenital defects connected with
      chromosome abnormalities: phenotype-karyotypic relations and genetic markers].
AB  - Computerized comparisons of phenotypes observed in different kinds of chromosomal
      imbalance and presented in the form of sparse matrices of traits were made to
      study the specificity of the indicated phenotypes, the possibility of
      differential diagnosis of the clinically similar forms, the presence of genetic
      markers, and the correspondence of the compared phenotypes to syndrome criteria.
      Stable enough, though variable trait associations characteristic of definite
      forms of imbalance of chromosomes 4, 5 and 9 were revealed, which were especially
      manifest when the respective trait frequency profiles were compared. Phenotypic
      distinction of 9p- and 11q-segmental monosomies was demonstrated and respective
      "phenotypic nuclei" were isolated. It has been shown that reliability of
      identification increases when the case to be analyzed is compared with a large
      enough number of primary descriptions. Analysis of 35 cases of 4p-segmental
      monosomies allowed the conclusion that Wolf-Hirschhorn syndrome is associated
      with deletion within 4 (p14-pter) region.

PMID- 1384875
TI  - [Current advances and present-day issues in mucoviscidosis].

PMID- 1384874
TI  - [Hereditary pathology load of the population and regional medical-genetic
      counseling].
AB  - Analysis of hereditary disease load of the populations with different genetic
      structure has demonstrated the necessity of a regional approach to the
      organization of the medico-genetic aid to the community. It has been shown that
      in Central Asia, the requirement of the medico-genetic aid is almost 2 times
      higher than in the Russian Federation. Bearing in mind the age-associated
      reproduction data, those differences are three times as higher. To make the work
      of the medico-genetic consultations more efficient, it is necessary to increase
      the portion of prospective counselling at the expense of an active approach to
      identifying patients in the populations.

PMID- 1384876
TI  - [Genetic effects of the action of small doses of ionizing radiation: problems of
      cellular response and approaches to their study].

PMID- 1384877
TI  - [Gene manifestations in negative man-made environment: a selective genetically
      determined sensitivity to asbestos].
AB  - Genetic polymorphism of the systems of haptoglobin, transferrin, alpha 1
      antitrypsin and complement C3 was investigated in patients with asbestosis and in
      healthy individuals who contacted with asbestos for a long time. The significant
      differences were discovered between the groups under comparison in the
      distribution of the phenotypic and genic frequencies in these loci. Simultaneous
      studies of the levels of these proteins depending on the phenotype demonstrated
      differentiation of the patients and healthy subjects according to the mean values
      and dispersions. The data obtained provide evidence in favour of occupational
      selection as regards the genetic factors investigated.

PMID- 1384878
TI  - [Medical Genetics Center of the Russian AMS: retrospective, status quo,
      perspectives].
AB  - The paper is concerned with the brief history of the Institute of Medical
      Genetics, USSR AMS. Recently it has been reorganized to the USR AMS Research
      Center of Medical Genetics which consists of two Institutes: the Institute of
      Human Genetics and the Institute of Clinical Genetics. The list of the
      departments and laboratories of both Institutes, their research programs and
      projects are summarized. The research programs are under discussion.

PMID- 1384879
TI  - [Genetic aspects of the action of immunosuppressive agents].
AB  - The data were obtained formerly that mice of certain strains essentially differ
      in the sensitivity to the immunodepressive and antiproliferative action of the
      alkylating agents (so-called opposite strains: DBA/2--highly sensitive, BALB/c-
      resistant). It is shown in the present work that with the use of the other non
      alkylating immunodepressive agents (cytarabine, cyclosporin A, dexamethasone)
      that differ in the action mode, DBA/2 mice retain a high sensitivity whereas
      BALB/c mice a low sensitivity to all the immunodepressants. The sensitivity to
      the immunodepressive action in vivo directly correlates with that of the
      immunocompetent cells in vitro. Potential mechanisms determining the same type
      sensitivity to diverse immunodepressant in mice belonging to the above-indicated
      genotypes are under discussion.

PMID- 1384880
TI  - [Use of the calculation of the micronuclei in human cells in the detection of
      cytogenetic injuries by environmental factors].
AB  - The review is concerned with an analysis of the data reported in this country and
      abroad on the use of micronuclei calculation for revealing cytogenetic injuries
      by environmental factors. It has been shown that the micronucleus test possesses
      a rather high sensitivity, provides information and affords an objective
      judgement about the action of mutagenic environmental factors on man.

PMID- 1384881
TI  - [Assessment of total mutagenic activity of harmful factors of the industrial
      environment at the metallurgy plants of South Ural].
AB  - Harmful factors of the industrial environment of the steel plants are represented
      by sulfur- and arsenic-containing compounds, nitrogen and carbon oxides, aerosols
      of heavy and rare metals, fluorine compounds whose concentrations exceed the
      maximum allowable ones in the air of the working place. The results of the
      cytogenetic examination of metallurgists attest to the pronounced total mutagenic
      activity of unfavourable factors of the industrial environment, among which the
      key role is played by arsenic, fluorine and heavy metal compounds.

PMID- 1384882
TI  - [International cooperation].

PMID- 1384883
TI  - [Arthrology: processes of differentiation and integration].
AB  - Modern arthrology, the science of disease of and damages to the joints, is a
      multidisciplinary section of medicine (rheumatology, orthopedics, pediatrics,
      allergology, oncology, and so forth). About 4% of the population of the earth
      suffer from different diseases of the joints. It is noted that the prevalence of
      joint pathology is non-uniform in different countries and continents. In the XX
      century, orthopedic arthrology, surgical methods of treatment are developing
      fairly intensively. The following issues have become a matter of growing concern:
      the effect of ionizing radiation, including low doses, on the articular
      cartilage, the role played by stress, disruption of the ecological balance in the
      genesis of arthrological disease, connection between dysplasia of the joints and
      subsequent dystrophic processes in them (the sequence dysplasia-dysplastic
      arthrosis), disturbances of the load of the joints as a pathogenetic mechanism of
      dystrophic and necrotic processes. In arthrology, special attention should be
      paid to aseptic necrosis of the jointed bones and to protruding coxarthrosis. The
      topicality of joint endoprosthetics is stressed as is the necessity of the
      setting up of the arthrological centres where endoprosthetics and restorative
      surgery might be up to standard. Unfortunately, the manufacture of joint
      endoprostheses in this country lags behind the requirements. Lately the problem
      of infantile and juvenile arthritides has become very urgent, posing the problem
      of the development of arthrological techniques for diagnosis and surgical
      treatment of the joints. The Academy of Medical Sciences of the Russian
      Federation should strengthen its coordinating and integrating roles in further
      development of arthrology.

PMID- 1384884
TI  - [Arthralgias and arthropathies in pathology of the central nervous system].

PMID- 1384886
TI  - [Immunomodulation in dystrophic diseases of the joints].
AB  - Immunological examinations of 357 patients with mixed arthritis, coxarthrosis and
      aseptic necrosis of the femoral head have revealed substantial immunopathological
      deviations requiring immunomodulation and influencing surgical outcomes, with
      inhibition or dysfunction of T and B cellular reactions, inversion of the
      regulatory index, remarkable autoimmune component, and bacterial sensitization in
      a considerable part of the examined. In addition to the conventional
      immunomodulating agents (levamisole, thymalin, T-activin, sodium nucleinate), it
      is recommended that hemodes and polyglucin may be used, provided they are chosen
      individually in vitro. The use of ELISA made it possible to reveal a direct
      strong correlation between the level of antibodies to glycolipid cartilaginous
      antigen and arteparon as well as a decrease of the number of antibodies in
      therapeutic administration of the drug. This suggests the immunological
      mechanisms of the action of arteparon, namely according to the principle of
      hapten inhibition.

PMID- 1384885
TI  - [Deforming gonarthrosis (questions of pathogenesis)].
AB  - Based on the biochemical, morphological, radionuclide, electron microscopy and
      arthroscopic data it has been established that there are significant changes in
      collagen proteins of the joint cartilage in the first stage of gonarthrosis
      deformans when degenerative and dystrophic alterations can only be seen in the
      joint cartilage. The determination of type II collagen which is commonly called
      procollagen brings something new in the understanding of the mechanism of
      degenerative dystrophic alterations in the joint cartilage. A considerable
      increase of a local proteolytic activity has been ascertained, which should be
      considered as the result of deep redox processes in the cartilage tissue.
      Gonarthrosis-associated microcirculatory disorders in the epiphyses with the
      development of vascular stasis, thrombosis, mural and total erythrocyte
      microaggregation cells, and perivascular hemorrhages have been confirmed. For the
      first time two forms of gonarthrosis (acute and latent) have been defined
      arthroscopically. The pathogenetic treatment methods have been elaborated in
      terms of the stages of the morphological changes identified.

PMID- 1384887
TI  - [A systemic approach to the surgical treatment of degenerative-dystrophic
      diseases of the hip joint].
AB  - Based on the experience gained with the surgical treatment of over 900 patients
      with different forms of degenerative dystrophic diseases of the hip joint the
      current principles of the choice of different types of surgical interventions
      were defined. As far as the patients with aseptic necrosis of the head of the
      femur are concerned, the main problem in this case lies in the early diagnosis of
      osteonecrosis. The surgical treatment is specified by the leading factor of the
      pathogenesis at every stage of the development of the process (vascular
      disorders, changes in the biomechanism of the joint). The planning of operations
      in patients with dysplastic coxarthrosis rests on the consideration of 8 basic
      factors that influence the disease by means of factorial analysis and
      determination of the prognostic estimations of the treatment efficacy.

PMID- 1384888
TI  - [Surgical treatment of rheumatoid lesions of the joints].
AB  - Thirty-four years of experience gained with the treatment of patients suffering
      from rheumatoid arthritis made it possible to develop a complex of orthopedic
      treatment methods (conservative and surgical) based on the clinical, x-ray and
      morphological classification. These methods allow arresting inflammation in the
      joint, preventing destruction of the joint and formation of concordant and
      disconcordant deformities, correcting deformities, recovering function, the
      patients activity, returning ability to active life, to social useful work, and
      minimizing the patients' disability.

PMID- 1384889
TI  - [Rheum-orthopedics in the system of complex treatment of rheumatoid arthritis].
AB  - The author presents an original conceptual scheme of the complex medical
      rehabilitation of patients with RA on the basis of the conservative and surgical
      treatment of RA (3,000 cases). Successful results were attained in 70% of cases
      (follow-up of 5 years).

PMID- 1384890
TI  - [Thyroliberin: new physiological effects and prospects of clinical use].
AB  - In addition to the well-known activities of TRH (stimulation of respiration,
      antidepressant action, increase of motility, antishock action, therapeutic
      effects against ataxia, and so forth), some new properties were established. TRH
      was found (1) to stimulate the contractility of lymph vessels in ultra-low doses
      and to be useful in the treatment of acute pancreatitis; (2) to normalize
      cerebral circulation in rats and neonates after asphyxia; (3) to improve the
      electrophysiological parameters of the retina and pigmented epithelium in rats
      and man, to exert a long-term positive influence on the health status of patients
      suffering from senile retinal macular dystrophy; (4) to potentiate the analgesic
      effect of low doses of morphine in a definite range of doses (analog PR-546). It
      is of paramount importance that most of the indicated activities of TRH may hold
      promise for clinical application.

PMID- 1384891
TI  - [Last-generation synthetic opioid analgesics as alternative to opiates in
      oncologic surgery].
AB  - The present-day problem is the development of effective methods of general
      anesthesia and postoperative anesthesia on the basis of nonopiate central
      analgesics possessing no hazardous side effects of opiates. A study was made of
      synthetic analgesics of the last generation as agents for intra- and
      postoperative anesthesia as compared with conventional opiates. It has been
      established that synthetic analgesics belonging to the class of opiate agonists
      antagonists, namely moradol and norphine, compare favourably enough with
      fentanyl. They are superior to fentanyl in antistressor properties, provide for a
      more powerful and longer analgesic effect and can replace conventional opiates in
      all the stages of surgical treatment of the patients. This is particularly
      important for the oncological clinic where opiates are to be preserved as reserve
      for the treatment of chronic painful syndrome.

PMID- 1384892
TI  - [Tasks of the Russian Academy of Medical Sciences in further development of
      medical sciences].

PMID- 1384893
TI  - [Blood platelet as a test system in the evaluation of neurohormonal imbalance in
      pregnant women with diabetes mellitus].
AB  - A study was made of platelet alpha 2- and beta 2-adrenoreceptors stimulated by
      adrenaline and alupent as well as of hemostatic system parameters the levels of
      ACTH, cortisol, glucagon and C-peptide in the blood of women with type I diabetes
      mellitus during pregnancy, surgical delivery, and the postoperative period. It is
      shown that the changes in the sensitivity of both subtypes of platelet
      adrenoreceptors are closely related to the activation of the stress-realizing
      systems and may serve as a test for estimating the intensity of neurohumoral
      imbalance both during pregnancy and surgical intervention. The sensitivity of
      platelet adrenoreceptors to agonists may be examined by a simple retention test
      allowing rapid information to be derived, which is of paramount importance under
      clinical conditions.

PMID- 1384894
TI  - [New automated information technology].

PMID- 1384895
TI  - Managing recurrent malignant pericardial effusions.

PMID- 1384896
TI  - Tachycardia during cisapride treatment.

PMID- 1384897
TI  - Epilepsy in the first 10 years of life: findings of the child health and
      education study.
AB  - OBJECTIVES: To identify children with afebrile seizures in a national cohort,
      classify the seizures, and document progress in the first 10 years of life.
      DESIGN: Population based birth cohort study. SETTING: The child health and
      education study, which includes 16,004 neonatal survivors (98.5% of infants born
      in the United Kingdom during one week of April 1970). SUBJECTS: 14,676 children
      for whom relevant information was available. MAIN OUTCOME MEASURES: Responses to
      parental and general practitioner questionnaires and hospital records at 5 and 10
      years after birth. RESULTS: 84 children (42 boys, 42 girls) had had one or more
      afebrile seizure (incidence 5.7/1000). 63 children (31 boys, 32 girls) had
      epilepsy (incidence 4.3/1000). 49 of 55 children had a second seizure within a
      year of the first. The commonest seizure types were tonic-clonic (42) and complex
      partial (25). A greater proportion of children with complex partial seizures had
      recurrences. Children who had infantile spasms or a mixed seizure disorder had a
      poor outcome. All six children who died had symptomatic seizures in the first
      year, but seizures were not the direct cause of death. CONCLUSIONS: The results
      of this study are probably representative of seizure patterns in the general
      population. Outcome after seizures is determined more by the underlying disease
      than by the seizures themselves.

PMID- 1384898
TI  - Cytotoxic drug and cytotoxic drug/G-CSF mobilization of peripheral blood stem
      cells and their use for autografting.
AB  - We analysed 99 courses of leukapheresis after the use of cytotoxic drugs or
      cytotoxic drugs plus G-CSF (cytotoxic/G-CSF) to mobilize peripheral blood stem
      cells (PBSC) in 68 patients with hematologic or solid malignancies. Mean yields
      of granulocyte-macrophage progenitor cells (CFU-GM) with cytotoxic/G-CSF
      mobilization were significantly higher than those with cytotoxic mobilization
      (18.6 vs 8.40 x 10(4)/kg). The optimal timing of collection was different between
      these two mobilizations; the mean number of days to a peak level of circulating
      CFU-GM after cytotoxic/G-CSF mobilization was less than that after cytotoxic
      mobilization (24.2 vs 27.7 days). The leukocyte level on the day of peak CFU-GM
      was significantly higher in cytotoxic/G-CSF mobilization than that in cytotoxic
      mobilization (mean 12.8 vs 2.7 x 10(9)/l), whereas the platelet level was not
      different (mean 132 vs 125 x 10(9)/l). Increasing patient age was not a major
      adverse factor for PBSC collection. Synchronous recovery of both leukocytes and
      platelets was critical for achieving a high CFU-GM yield in these two
      mobilizations. Following PBSC autotransplantation, the rate of trilineage
      hematologic reconstitution showed a significant correlation with the infused dose
      of CFU-GM, whether they were collected with cytotoxic or cytotoxic/G-CSF
      mobilization. These results suggest that G-CSF can expand the PBSC pool and that
      CFU-GM yield after cytotoxic/G-CSF mobilization may predict trilineage
      hemopoietic reconstitution after ABSCT, as well as cytotoxic mobilization.

PMID- 1384899
TI  - Increased yield of myeloid progenitor cells in bone marrow harvested for
      autologous transplantation by pretreatment with recombinant human granulocyte
      colony stimulating factor.
AB  - Pretreatment with haemopoietic cytokines prior to marrow harvest may result in
      improved quality of bone marrow harvested for autologous bone marrow
      transplantation (BMT). Such improvements may reduce the risk for graft failure
      and decrease time to engraftment. Patients undergoing autologous BMT received
      recombinant human G-CSF (rhG-CSF) immediately prior to marrow harvest. rhG-CSF
      was administered as daily subcutaneous injections for 5 days at 5 micrograms/kg
      body weight. Comparison of bone marrow samples before and after rhG-CSF treatment
      showed an increased bone marrow cellularity and a ninefold increase in the number
      of marrow leucocytes per volume aspirated. The mean marrow myeloid:erythroid
      ratio increased from 2.6 to 4.0. The mean numbers of immature (CD38 positive) and
      proliferating (CD71 positive) myeloid cells increased significantly from 41.6 to
      50.8% and from 17.0 to 34.8%, respectively. Other subsets studied, including CD34
      positive stem cells, were unchanged. The relative numbers of day 7 and 14
      granulocyte-macrophage colony-forming units (day 7/14 GM-CFU) were unchanged.
      Long-term marrow cultures revealed that the numbers of 'long-term culture
      initiating cells' were unchanged after rhG-CSF treatment in spite of the ninefold
      increase in cellularity. To date, five of the patients have been transplanted
      with autologous marrow harvested after rhG-CSF treatment. Time to trilineage
      engraftment was unchanged compared with historical controls. We conclude that
      pretreatment with rhG-CSF prior to marrow harvest may improve the graft by
      increasing the total number of myeloid lineage restricted progenitor cells,
      resulting in stable but not accelerated myeloid engraftment of autologous marrow.

PMID- 1384900
TI  - Characterization of chemotherapy mobilized peripheral blood progenitor cells for
      use in autologous stem cell transplantation.
AB  - Twenty patients were treated with chemotherapy to mobilize progenitors into the
      blood. Peripheral blood stem cells were quantitated in peripheral blood or
      leukapheresis products using colony assays and flow cytometric measurement of
      CD34+ cells. In four patients where complete sets of serial samples were
      obtained, the appearance of CD34+ cells preceded the increase in CFU-GM by 24-48
      h. Peak levels of CD34+ cells ranged from 0.6-5% and coincided with the peak
      increase in CFU-GM. Mobilized CD34+ cells contained subsets expressing CD33,
      CD13, CD45RA, CD38, HLA-DR, CD61 and CD41. Subsets of CD34+ cells expressing
      CD33, CD13, or CD45RA represent committed myeloid progenitors. In contrast to
      bone marrow CD34+ cells, few mobilized CD34+ cells expressed CD71, CD7, CD19 or
      CD10. Prompt engraftment of granulocytes greater than 500 x 10(6)/l at a median
      of 13 days and platelets greater than 50 x 10(9)/l at a median of 15 days was
      observed in patients reconstituted with mobilized cells. These data indicate that
      CD34+ cells mobilized during recovery from chemotherapy are predominantly myeloid
      in phenotype and contain few actively proliferating cells or cells with lymphoid
      phenotypes.

PMID- 1384901
TI  - Expression of phosphatidylinositol anchored membrane proteins in paroxysmal
      nocturnal haemoglobinuria after bone marrow transplantation.
AB  - A 20-year-old male with severe bone marrow failure associated with paroxysmal
      nocturnal haemoglobinuria (PNH) underwent an allogeneic bone marrow
      transplantation (BMT). Flow cytometric analysis of phosphatidylinositol (PI)
      anchored membrane proteins prior to BMT showed a markedly reduced expression of
      monocyte CD14 and neutrophil CD16 molecules. On day +17 after BMT expression of
      both antigens reached normal values and remained stable throughout a follow-up
      period of 10 months, thus confirming the eradication of the PNH clone. To date,
      this is the first case in which normal expression of PI-anchored proteins after
      BMT is reported.

PMID- 1384902
TI  - Collection of peripheral blood stem cells mobilized by high-dose Ara-C plus VP-16
      or aclarubicin followed by recombinant human granulocyte-colony stimulating
      factor.
AB  - We developed an effective method for harvesting large numbers of peripheral blood
      stem cells (PBSC) for use in autotransplantation. Twenty patients with
      hematological malignancies were treated with high doses of Ara-C (12 g/m2) and VP
      16/aclarubicin followed by administration of rhG-CSF (50 micrograms/m2). The
      optimal time for starting PBSC collection was determined by monitoring the CD34
      positive stem cells in blood using immunomagnetic beads. PBSC were collected with
      a CS-3000 blood cell separator. A total blood volume between 7000 and 9000 ml was
      processed in each apheresis. Under these conditions, a total of 64 apheresis
      procedures was performed in the 20 patients. The mean numbers of mononuclear
      cells and of CFU-GM harvested per apheresis were 4.1 x 10(8)/kg and 110 x
      10(4)/kg, respectively. A number of CFU-GM sufficient for engraftment (> 30 x
      10(4)/kg) could be harvested by a single apheresis in 15 of the 20 patients. So
      far, 11 patients have been transplanted with PBSC and obtained rapid
      hematopoietic recovery. The median time to recover neutrophils more than 0.5 x
      10(9)/l was 10 days, and that for platelets 50 x 10(9)/l was 11 days. This method
      for harvesting large numbers of PBSC allows safer autotransplantation in patients
      with chemoradiosensitive tumors, and is applicable to older patients.

PMID- 1384903
TI  - [Non-surgical treatment of benign prostatic hypertrophy. Current status of the
      problem].
AB  - Benign prostatic hypertrophy is a highly prevalent disease, with a significant
      morbidity. Classical surgical therapy (open or transurethral adenomectomy) is
      very effective, but not without risks and complications. Better understanding of
      the pathogenesis of the disease have led to the development of several
      alternative treatments. Hormonal treatments are briefly reviewed, especially the
      preliminary results obtained with the 5-alpha-reductase inhibitors.

PMID- 1384904
TI  - The effects of calcitonin gene-related peptide on formation of intra-articular
      oedema by inflammatory mediators.
AB  - 1. The temporal and quantitative effects of inflammatory mediators on plasma
      extravasation in the rat knee were investigated by use of a perfusion technique.
      2. Intra-articular perfusion of substance P (SP), bradykinin or histamine over a
      5 min test period produced rapid-onset and prolonged plasma extravasation in a
      dose-dependent fashion. The rank order of potency was bradykinin greater than SP
      greater than histamine. 3. Calcitonin gene-related peptide (CGRP) did not induce
      plasma extravasation but enhanced substance P-induced plasma extravasation in a
      dose-dependent fashion. A 5 min co-perfusion of the two agents produced short
      term enhancement lasting 10 min while continuous co-perfusion produced
      enhancement for the duration of the perfusion. 4. A 5 min perfusion of CGRP
      enhanced plasma extravasation when co-perfused with bradykinin but not histamine.
      However, when CGRP and histamine were continuously co-perfused over a 20 min test
      period, an enhanced response was apparent. 5. The results indicate that intra
      articular perfusion of CGRP enhances synovial plasma extravasation induced by
      agents that increase vascular permeability, but suggest that the response is not
      uniform and is critically dependent on the duration of perfusion within the
      joint.

PMID- 1384905
TI  - Phosphodiesterase inhibition in ventricular cardiomyocytes from guinea-pig
      hearts.
AB  - 1. The present study compared the cyclic nucleotide phosphodiesterase (PDE)
      activities in cardiomyocytes and ventricular cardiac tissue from guinea-pigs. The
      aim of the study was to determine whether PDE activities in ventricular tissue
      accurately reflect the isoenzymes present in cardiomyocytes. 2. In homogenates of
      cardiomyocytes and multicellular ventricular tissue, four distinct soluble PDE
      activities could be separated by DEAE-sepharose chromatography. 3. In
      multicellular cardiac tissue as well as in cardiomyocyte preparations, adenosine
      3':5'-cyclic monophosphate (cyclic AMP) PDE isoenzymes I-IV were comparable in
      terms of substrate affinities, and inhibition or stimulation by guanosine 3':5'
      cyclic monophosphate (cyclic GMP). However, in cardiomyocytes the Vmax values of
      PDE I-IV were lower by a factor of about 2 to 7 and the basal activities were
      lower by a factor of about 3 to 5 as compared to multicellular cardiac tissue. 4.
      To investigate whether the PDE I-IV activities were similarly inhibited by PDE
      inhibitors in both preparations, we studied the effects of 3-isobutyl-1
      methylxanthine (IBMX), UD-CG 212 Cl (2-(4-hydroxy-phenyl)-5-(5-methyl-3-oxo-4, 5
      dihydro-2H-6-pyridazinyl)benzimidazole HCl) and rolipram. UD-CG 212 Cl was a
      selective PDE III inhibitor in cardiomyocytes (IC50 0.3 mumol l-1) and in
      ventricular tissue (IC50 value 0.1 mumol l-1). Rolipram selectively inhibited PDE
      IV in cardiomyocytes (IC50 1.4 mumol ml-1) and in ventricular tissue (IC50 1.1
      mumol l-1) whereas IBMX was a nonselective PDE inhibitor in both preparations.5.
      It is concluded that the PDE isoenzymes I-IV from multicellular ventricular
      tissue can be used as a representative system for investigating PDE inhibiting
      properties of PDE inhibitors in the myocardium since comparable PDE isoenzymes I
      IV exist in guinea-pig ventricular cardiomyocytes and multicellular ventricular
      tissue.

PMID- 1384906
TI  - Differential modulation of extracellular levels of 5-hydroxytryptamine in the rat
      frontal cortex by (R)- and (S)-zacopride.
AB  - 1. The ability of various anxiolytic and potential anxiolytic agents to modify 5
      hydroxytryptamine (5-HT) release in the frontal cortex of the rat was assessed by
      the microdialysis technique. 2. The benzodiazepine receptor agonist, diazepam
      (2.5 mg kg-1, i.p.), the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)
      tetralin (8-OH-DPAT, 0.32 mg kg-1, s.c.) and the 5-HT1A receptor partial agonist
      buspirone (4.0 mg kg-1, i.p.) maximally reduced extracellular levels of 5-HT in
      the rat frontal cortex by approximately 50-60%, 70-80% and 30-40%, respectively.
      3. (R)-zacopride (1.0-100 micrograms kg-1, i.p.) dose-dependently reduced
      extracellular levels of 5-HT in the rat frontal cortex (approximately 80% maximal
      reduction) whereas the other 5-HT3 receptor antagonists ondansetron (10
      micrograms kg-1, i.p.) and (S)-zacopride (10-100 micrograms kg-1, i.p.) were
      ineffective. 4. In contrast to (S)-zacopride (100 nM; administered via the
      microdialysis probe), (R)-zacopride (1.0-100 nM; administered via the
      microdialysis probe) induced a concentration-dependent reduction in extracellular
      levels of 5-HT in the rat frontal cortex (approximately 70% maximal reduction).
      5. In contrast to ondansetron (100 micrograms kg-1, i.p.), (S)-zacopride (10-100
      micrograms kg-1, i.p.) dose-dependently reversed the (R)-zacopride (10 micrograms
      kg-1, i.p.) induced reduction in extracellular levels of 5-HT in the rat frontal
      cortex. The highest dose of (S)-zacopride (100 micrograms kg-1, i.p.) completely
      prevented the (R)-zacopride response.In addition, (S)-zacopride (100 nM;
      administered via the microdialysis probe) attenuated the inhibitory action of (R)
      zacopride (10 nM; administered via the microdialysis probe) on extracellular
      levels of 5-HT in the rat frontal cortex.6. In conclusion, the present study
      provides further evidence of the ability of diazepam, 8-OH-DPAT and buspirone to
      reduce the activity of the central 5-hydroxytryptaminergic system in vivo.
      Furthermore,the results indicate that the ability of (R)-zacopride to reduce the
      in vivo release of 5-HT in the rat frontal cortex does not correlate with its 5
      HT3 receptor antagonism. However, the differential affinity of (R)- and (S)
      zacopride for a (S)-zacopride-insensitive (R)-zacopride site in rat cerebral
      cortex mirrors the relative activity of the two zacopride stereoisomers to modify
      the in vivo release of 5-HT in the frontal cortex of the rat and their ability to
      release suppressed behaviour in animal models of anxiety.

PMID- 1384907
TI  - Tachykinin receptors in the guinea-pig renal pelvis: activation by exogenous and
      endogenous tachykinins.
AB  - 1. The contractile response to substance P, neurokinin A, selective agonists for
      the NK1, NK2 and NK3 tachykinin receptors and the activity of receptor-selective
      antagonists has been investigated in circular muscle strips of the guinea-pig
      isolated renal pelvis in the presence of indomethacin (3 microM). 2. Neurokinin A
      was the most potent agonist tested, being about 32 times more potent than
      substance P. The action of both substance P and neurokinin A was enhanced by
      peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). The
      selective NK2 receptor agonist [beta Ala8] neurokinin A (4-10), was slightly less
      potent and effective than neurokinin A itself. The selective NK1 receptor agonist
      [Sar9] substance P sulphone was effective at low (nM) concentrations but its
      maximal effect did not exceed 30% of maximal response to substance P or
      neurokinin A. The NK3-selective agonist [MePhe7] neurokinin B was effective only
      at high (microM) concentrations. 3. The pseudopeptide derivative of neurokinin
      A(4-10), MDL 28,564, displayed a clear-cut agonist character, although it was
      less potent than neurokinin A. 4. The responses to roughly equieffective (25-35%
      of maximal response) concentrations of [beta Ala8] neurokinin A (4-10), MDL
      28,564 and [MePhe7] neurokinin B were antagonized to a similar extent by MEN
      10,376 (3 microM), a selective NK2 tachykinin receptor antagonist, while the
      response to [Sar9] substance P sulphone was unchanged. 5. The response to [Sar9]
      substance P sulphone was inhibited by the NK1 receptor-selective antagonist, GR
      82,334 (3 microM) while the response to [beta Ala8] neurokinin A (4-10) was
      unchanged. 6. The selective NK2 receptor antagonists MEN 10,376, L 659,877 and R
      396 antagonized competitively the response to [PAla8] neurokinin A (4-10) with
      the following rank order of potency (pA2 values in parentheses): MEN 10,376
      (7.41)>L 659,877 (7.15)>R 396 (6.43). MEN 10,376 and L 659,877 also competitively
      antagonized the response to neurokinin A, although with lower potency as compared
      to the selective NK2 receptor agonist.7. MEN 10,376, L 659,877 and R 396 reduced
      in a concentration-dependent manner the contractile response produced by
      electrical field stimulation (1 Hz, 100 V, 0.25 ms pulse width, trains of 10 s).
      The rank order of potency of NK2 receptor antagonists in blocking the response to
      electrical stimulation (MEN 10,376> L 659,877> R 396) closely mimicked their
      potency in antagonizing exogenous tachykinins.8. The inhibitory effect of MEN
      10,376 toward responses produced by electrical field stimulation was
      significantly reduced when tested in the presence of peptidase inhibitors, which
      increased significantly the response to nerve stimulation.9. GR 82,334 (3 pM) did
      not significantly affect the response to nerve stimulation in untreated
      preparations and slightly reduced it in the presence of peptidase inhibitors.10.
      We conclude that both NK, and NK2 receptors mediate the contractile effect of
      tachykinins in the circular muscle of the guinea-pig renal pelvis and that the
      response ascribable to NK2 receptor stimulation is larger than that ascribed to
      NK, receptor stimulation. The NK2 receptor in the guinea-pig renal pelvis belongs
      to the same subtype previously identified in the rabbit pulmonary artery. NK2
      receptors play a dominant role in the physiological response determined by the
      release of endogenous tachykinins and a contribution of NKI receptors becomes
      evident after inhibition of peptide degradation.

PMID- 1384909
TI  - The actions of two sensory neuropeptides, substance P and calcitonin gene-related
      peptide, on the canine hepatic arterial and portal vascular beds.
AB  - 1. The two peptides, calcitonin gene-related peptide (CGRP) and substance P (SP)
      were administered individually as bolus injections into the separately perfused
      hepatic arterial and portal vascular beds of the anaesthetized dog to assess
      their actions and relative molar potencies at these sites. 2. CGRP caused an
      immediate dose-related increase in hepatic arterial flow when injected close
      arterially, reflecting a fall in resistance. This vasodilator effect was slightly
      increased by the prior administration of the selective beta 2-adrenoceptor
      antagonist, ICI 118,551. 3. On a molar basis, CGRP was more potent as an hepatic
      arterial vasodilator than the non-selective beta-adrenoceptor agonist,
      isoprenaline (Iso). 4. Intra-portal injection of CGRP also evoked hepatic
      arterial vasodilatation unaccompanied by other cardiovascular changes. 5. CGRP in
      doses up to 10 nmol had no effect on portal vascular resistance when administered
      intra-portally. 6. SP evoked a rapid, dose-related increase in hepatic arterial
      flow when injected intra-arterially. The molar ED50 for this hepatic
      vasodilatation was 40.2 fmol, significantly less than the ED50 for either CGRP or
      Iso. SP was the most potent hepatic arterial vasodilator yet examined. The
      vasodilator effect of SP was slightly potentiated by prior beta 2-adrenoceptor
      blockade. 7. SP caused hepatic arterial vasodilatation when administered by intra
      portal injection; its absolute and relative potency was much reduced. 8. SP when
      injected intra-portally caused a graded increase in hepatic portal inflow
      resistance. The molar potency for this portal vasoconstriction was significantly
      greater than that for noradrenaline (NA); however, the maximum increase in portal
      resistance was significantly less to SP than to NA.9. In view of the location of
      the peptides CGRP and SP within the afferent innervation of the liver, it is
      proposed that they play an important function in controlling the hepatic
      microvasculature in response to sensory stimuli, particularly those arising from
      changes in portal blood composition secondary to change in metabolic activity
      within the gastrointestinal tract (GIT).10. Since the peptides are released from
      the GIT into the hepatic portal inflow, they may modify hepatic arterial blood
      flow, the extent of which is related to events within the GIT.

PMID- 1384908
TI  - Participation of protein kinase C in endothelin-1-induced contraction in rat
      aorta: studies with a new tool, calphostin C.
AB  - 1. Calphostin C at 10(-6) M was shown to be selective and highly effective in
      inhibiting contractile responses of rat aortae to 12-o-tetradecanoylphorbol-13
      acetate, while it had no effect on contractile responses to elevated KCl. 2. In
      the rat aorta, endothelin-1 (ET-1) developed a sustained tonic contraction dose
      dependently in both normal Ca(2+)-containing Krebs and Ca(2+)-free Krebs
      containing 1 mM EGTA. Calphostin C (10(-6) M), a selective protein kinase C
      inhibitor, antagonized the maximal tensions for cumulative addition of 10(-8) M
      ET-1 by 13.2% in Ca(2+)-containing medium and 25.8% in Ca(2+)-free Krebs
      containing 1 mM EGTA. 3. In both Ca(2+)-containing medium and Ca(2+)-free Krebs
      containing 1 mM EGTA, precontraction with 10(-8) M ET-1 had no effects on the
      contractile response to subsequently added 10(-6) M 12-o-tetradecanoylphorbol-13
      acetate (TPA), an activator of protein kinase C. 4. In Ca(2+)-free Krebs
      containing 1 mM EGTA, precontraction with 10(-6) M TPA potentiated the
      contractile response to subsequently added 10(-8) M ET-1, whereas this
      potentiation was abolished by pretreatment with 10(-6) M calphostin C. The
      mechanism of the TPA-induced potentiating effect remains to be determined. 5.
      These results suggest that the participation of protein kinase C in the 10(-8) M
      ET-1-induced contraction may be 13.2% and 25.8% in the presence and absence of
      extracellular Ca2+, respectively, and that mechanisms other than protein kinase C
      may be predominantly responsible for ET-1-induced tonic contraction.

PMID- 1384910
TI  - Effects of the bradykinin antagonist, HOE 140, in experimental acute
      pancreatitis.
AB  - 1. The novel bradykinin antagonist, HOE 140, completely blocked the fall in
      rabbit blood pressure caused, not only by i.v. bradykinin, but also by i.v.
      kallikrein. This shows that both the effects of exogenously administered
      bradykinin and those of endogenously released kinins are antagonized by HOE 140.
      2. Acute pancreatitis was induced in rats by i.v. infusion of the cholecystokinin
      analogue, caerulein. This treatment resulted in massive oedema of the pancreas,
      increased activities of amylase and lipase in serum and a characteristic,
      biphasic fall in blood pressure. 3. HOE 140 prevented the caerulein-induced
      pancreatic oedema and the second phase of hypotension whereas NPC 349, a widely
      used, but short-acting, bradykinin antagonist did not show a significant
      inhibition. HOE 140, in contrast to its inhibitory effects on caerulein-induced
      pancreatic oedema and hypotension, significantly augmented the increases in
      amylase and lipase activities in serum. 4. It is concluded that in this model of
      acute pancreatitis, the release of kinins induces pancreatic oedema and
      hypotension. Prevention by HOE 140 of the kinin-induced oedema allows the
      pancreatic enzymes to leave the tissue without hindrance and thus will diminish
      subsequent pathological events. It is suggested that the results obtained with
      the highly potent and long-acting bradykinin antagonist, HOE 140, provide a
      pharmacological basis for a clinical trial in acute pancreatitis.

PMID- 1384912
TI  - The actions of capsaicin applied topically to the skin of the rat on C-fibre
      afferents, antidromic vasodilatation and substance P levels.
AB  - 1. Single applications of solutions of capsaicin were made to the intact skin of
      anaesthetized rats and the effects on cutaneous blood flow and the firing of C
      nociceptor afferents determined. Blood flow was measured by laser-Doppler
      flowmetry. C-fibre activity was recorded from filaments dissected from the
      saphenous nerve. 2. Following the application of a capsaicin solution
      (concentration > or = 1 mM) to rat saphenous skin, low frequency firing occurred
      in C-polymodal nociceptors that sometimes continued for > 10 min. At the some
      time, large increases in skin blood flow occurred exceeding 300% in some
      instances. 3. After the initial excitation, some C-polymodal nociceptors lost
      their sensitivity to pressure whilst their sensitivity to heat was lost or
      enhanced depending on the vehicle used. 4. Sensitivity of C-polymodal nociceptors
      to heat recovered in < 1 day following a single application of 33 mM capsaicin.
      Thresholds to mechanical pressure, however, were still significantly elevated by
      123% on day 1, but had recovered on day 2. 5. Vasodilatation in response to
      saphenous nerve stimulation ('antidromic vasodilatation') was significantly
      reduced by 35%, 2 days after a single application of 33 mM capsaicin, but was
      normal at 4 days. 6. Following a single application of 33 mM capsaicin, skin
      substance P levels fell to only half the normal value at day 1 and remained at
      this level throughout the 4 day period examined. 7. It is suggested that the
      ability of relatively low concentrations of capsaicin to desensitize C-fibre
      nociceptors may underlie the analgesic action of topical capsaicin in man.

PMID- 1384911
TI  - Nitric oxide synthase responsible for L-arginine-induced relaxation of rat aortic
      rings in vitro may be an inducible type.
AB  - 1. Characteristics of L-arginine-induced non-endothelial nitric oxide (NO)
      formation in rat isolated thoracic aorta were investigated. 2. Relaxation to L
      arginine in arterial rings devoid of endothelium developed about 2 h after the
      first challenge with L-arginine and reached a maximum after a further 4 h of
      incubation. 3. After the arteries had relaxed in response to L-arginine,
      guanosine 3':5'-cyclic monophosphate (cyclic GMP) production was stimulated. In
      fresh arteries that had not yet relaxed in response to L-arginine, L-arginine
      failed to elevate cyclic GMP levels. 4. Glucocorticoids, actinomycin D and
      polymyxin B prevented the development of L-arginine-induced relaxation and L
      arginine-stimulated increase in cyclic GMP formation. 5. Once L-arginine-induced
      relaxation developed, these agents no longer suppressed the relaxation and
      increase in cyclic GMP formation to L-arginine. 6. From these results, it is
      suggested that in the isolated thoracic aorta of the rat, endotoxin in the medium
      triggers induction of a non-endothelial NO synthase during prolonged incubation,
      which accelerates production of NO from added L-arginine to cause relaxation of
      the arteries via cyclic GMP. Glucocorticoids and protein synthesis inhibitors may
      prevent induction of NO synthase. It is suggested that the NO synthase mediating
      the production of muscle-derived NO from L-arginine is an inducible type.

PMID- 1384913
TI  - Control of cyclic AMP levels in primary cultures of human tracheal smooth muscle
      cells.
AB  - 1. [3H]-adenosine 3':5'-cyclic monophosphate ([3H]-cyclic AMP) responses were
      studied in primary cultures of human tracheal smooth muscle cells derived from
      explants of human trachealis muscle and in short term cultures of acutely
      dissociated trachealis cells. 2. Isoprenaline induced concentration-dependent
      [3H]-cyclic AMP formation with an EC50 of 0.2 microM. The response to 10 microM
      isoprenaline reached a maximum after 5-10 min stimulation and remained stable for
      periods of up to 1 h. After 10 min stimulation, 1 microM isoprenaline produced a
      9.5 fold increase over basal [3H]-cyclic AMP levels. The response to isoprenaline
      was inhibited by ICI 118551 (10 nM), (apparent KA 1.9 x 10(9) M-1) indicating the
      probable involvement of a beta 2-adrenoceptor in this response in human cultured
      tracheal smooth muscle cells. However, with 50 nM ICI 118551 there was a
      reduction in the maximum response to isoprenaline. Prostaglandin E2 also produced
      concentration-dependent [3H]-cyclic AMP formation (EC50 0.7 microM, response to 1
      microM PGE2 6.4 fold over basal). 3. Forskolin (1 nM - 100 microM) induced
      concentration-dependent [3H]-cyclic AMP formation in these cells. A 1.6 fold
      (over basal) response was also observed following stimulation with NaF (10 mM).
      4. The nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      (IBMX) (0.1 mM) and the type IV, cyclic AMP selective, phosphodiesterase
      inhibitor rolipram (0.1 mM) both elevated basal [3H]-cyclic AMP levels by 1.8 and
      1.5 fold respectively. IBMX (1-100 microM) and low concentrations of rolipram (<
      10 microM), also potentiated the response to 1 microM isoprenaline. Inhibitors of
      the type III phosphodiesterase isoenzyme (SK&F 94120 and SK&F 94836) were without
      effect upon basal or isoprenaline-stimulated cyclic AMP responses in these
      cells.5. Carbachol (1 nM-I 00 microM) produced concentration-dependent inhibition
      of the [3H]-cyclic AMP response to 1 microM isoprenaline in human cultured
      tracheal smooth muscle cells (IC50 0.24 JM). Carbachol(1 JM) inhibited the [3H]
      cyclic AMP response to 1 JM isoprenaline by 60%. This effect of carbachol was
      itself inhibited by atropine (50 nM) (KA 2.3 x 109 M-') indicating the
      involvement of a muscarinic receptor.6. These results show that primary cultures
      of human tracheal smooth muscle cells demonstrate cyclic AMP responses to direct
      receptor stimulation, adenylyl cyclase activation and inhibition with
      nonselective and type IV-selective cyclic AMP phosphodiesterase isoenzyme
      inhibitors, and that the cyclic AMP response to isoprenaline can be inhibited by
      muscarinic receptor stimulation.

PMID- 1384914
TI  - Tachykinin receptors in rabbit airways--characterization by functional,
      autoradiographic and binding studies.
AB  - 1. In many species, both NK1 and NK2 tachykinin receptors appear to be important
      in mediating the contraction of airway smooth muscle. We have examined the
      distribution and characterization of receptors for tachykinins in rabbit airways
      using functional length tension studies, autoradiography and radioligand binding
      studies. 2. Contractile responses to tachykinins were elicited in four different
      areas of the respiratory tree--trachea, and three progressively more distal areas
      of the right bronchus. The NK2 receptor-preferring agonists, neurokinin A (NKA),
      neuropeptide gamma (NP gamma) and the NK2-selective [Lys5 MeLeu9, Nle10]-NKA(4
      10) [NKA (4-10) analogue] produced similar contraction in all four areas.
      Substance P (SP) and the NK1-selective [Sar9,Met(O2)11]-SP (Sar-SP) exhibited a
      marked location-dependence in the magnitude of contraction, producing minimal
      contraction in the trachea and more proximal bronchi with contractions becoming
      progressively larger in the more distal airways. Senktide (which is selective for
      the NK3 receptor) produced negligible contraction in all areas. 3. The NK2
      selective antagonist, MDL29,913, was a weak antagonist of NKA and NKA(4-10)
      analogue. At a concentration of 2 microM, it produced a small but significant
      shift in the response curve to NKA and a greater shift (8 fold) in the curve to
      NKA(4-10) analogue, but it had no effect on responses to Sar-SP. The non peptide
      NK1 receptor antagonist, CP-96,345, was also unexpectedly weak in this
      preparation. The pD2 value for Sar-SP was decreased 27 fold by CP-96,345 at a
      concentration of 1 microM, without alteration in the maximum response.4.
      Autoradiographic binding sites to ['251I]-NKA were sparse over smooth muscle in
      proximal airway preparations and markedly increased in density in the more distal
      airways. There was negligible binding over vascular smooth muscle and
      epithelium.5. Radioligand binding studies revealed binding to ['251I]-NKA which
      was 82% specific. The order of potency for inhibition of ['251I]-NKA binding was
      SP> = Sar-SP> NKA = NPy>CP-96,345> NKA(4-10) analogue >NKB>>>MEN 10207 (the NK2
      subtype selective antagonist) >MDL 29,913> senktide. This profile indicates
      binding predominantly to NK, receptors.6. These results suggest that there are at
      least two types of tachykinin receptors in rabbit airways, a population of NK,
      receptors, the density of which is greatest in the periphery and, in addition,
      NK2 receptors which are uniformly distributed throughout the airways. These
      receptors have unusual characteristics in that the NK, antagonist, CP-96,345 and
      the NK2 antagonist, MDL 29,913 respectively exhibited only weak potency.

PMID- 1384915
TI  - Thimerosal blocks stimulated but not basal release of endothelium-derived
      relaxing factor (EDRF) in dog isolated coronary artery.
AB  - 1. The effect of an acetly-coA lysolecithin acyltransferase inhibitor,
      thimerosal, on the release of endothelium-derived relaxing factor (EDRF) was
      examined in the greyhound isolated coronary artery. 2. Thimerosal (1-10 microM)
      relaxed fully, ring segments of coronary artery which were contracted with the
      thromboxane A2-mimetic, U46619 (30 nM). The response was endothelium-dependent,
      slow in both onset and time to reach maximum. The maximum relaxation to the
      highest concentration of thimerosal (10 microM) was maintained for 10-20 min
      before the tissue slowly regained active force (1-2 h) to the same or higher
      level as that prior to the addition of thimerosal. At this time the endothelium
      dependent relaxation responses to acetylcholine (ACh), substance P (SP),
      bradykinin (BK) and the calcium ionophores, ionomycin and A23187 were abolished.
      The endothelium-dependent contractions to the nitric oxide synthase inhibitors,
      NG-nitro-L-arginine (L-NNA; 10-100 microM) and NG-monomethyl-L-arginine (L-NMMA:
      10-100 microM), however, were unaffected. 3. Thimerosal (10 microM) did not
      affect the relaxation curve to sodium nitroprusside (SNP) nor the contraction
      curve to the thromboxane A2-mimetic, U46619. 4. Both the relaxation response to
      thimerosal and the selective block of the relaxation responses to stimulated EDRF
      release were unaffected by either indomethacin (10 microM) or superoxide
      dismutase (150 u ml-1). 5. L-NNA (100 microM) significantly blocked the
      relaxation curves to thimerosal and A23187 but not that to SNP.6. Abolition of
      stimulated EDRF-mediated responses with thimerosal was unlikely to result from
      maximal and maintained stimulation of EDRF release even when active U46619
      induced force had returned to pre-thimerosal levels, since the relaxation curves
      to glyceryl trinitrate (GTN) and SNP were markedly attenuated in the presence of
      SNP and GTN respectively when active force was restored with endothelin-1 (ET
      1).7. Melittin (1 microM), ionomycin (1 microM) and A23187 (1 microM) each had
      selective effects on stimulated but not basal EDRF responses, similar to those of
      thimerosal.8. We propose that stimulated but not 'basal' release of EDRF is
      dependent on the release of arachidonic acid or one of its non-cyclo-oxygenase
      metabolites, possibly by Ca2'-dependent activation of phospholipase A2.

PMID- 1384917
TI  - Can serum prostate-specific antigen replace bone scintigraphy in the follow-up of
      metastatic prostatic cancer?
AB  - Bone scintigraphy is the most sensitive imaging technique for the initial
      detection of bone metastases and is widely used in the staging of prostatic
      cancer. This study was performed to assess whether the development of further
      bone metastases can be detected by serial measurements of the serum glycoprotein
      prostate-specific antigen (PSA) as an alternative to follow-up scintigraphy. The
      bone scintigrams and PSA levels of 101 patients with metastatic prostate cancer
      entered into two therapeutic trials have been reviewed. Serial results of both
      investigations were available in 59 cases. In three cases new bone deposits were
      observed without a corresponding rise in PSA. In two other cases the scintigrams
      were considered to be suspicious of progression with no change in PSA levels;
      however, further follow-up indicated that these changes were not due to
      metastases. In 13 cases PSA levels were rising in advance of new deposits on the
      scintigrams. In the remaining 41 cases the PSA levels and scintigraphic findings
      paralleled each other. We conclude that serial estimation of PSA levels is a
      simpler marker for disease progression than bone scintigraphy in metastatic
      prostatic cancer, but that neither technique in isolation gives complete
      accuracy.

PMID- 1384918
TI  - Is urethral pressure profilometry useful in the preoperative assessment of benign
      prostatic hyperplasia?
AB  - The principal aim of this study was to provide an objective assessment of the
      potential role of urethral pressure profilometry as a technique for assessing
      prostatic size by direct comparison with endoscopic assessment of prostatic
      length and computed tomographic measurement of prostatic volume and length. There
      was a poor correlation between pre-operative prostatic length and amount resected
      in the operating theatre. The results obtained with urethral pressure
      profilometry correlated poorly with those obtained using the other techniques,
      and cannot therefore be relied upon in routine clinical practice. Although there
      was good correlation between the length of the prostate and prostatic size,
      assessed by pre-operative computed tomography, this correlated poorly with the
      amount of tissue resected at operation. Further studies need to be conducted to
      compare objectively the completeness of prostatic resection with the outcome
      following prostatectomy.

PMID- 1384916
TI  - Effects of nitric oxide synthase inhibitors, L-NG-nitroarginine and L-NG
      nitroarginine methyl ester, on responses to vasodilators of the guinea-pig
      coronary vasculature.
AB  - 1. The effects of L-NG-nitroarginine (L-NOARG) and L-NG-nitroarginine methyl
      ester (L-NAME) on vasodilatation induced by ATP, substance P, 5-hydroxytryptamine
      (5-HT), bradykinin and sodium nitroprusside (SNP) were examined in the guinea-pig
      coronary bed, by use of a Langendorff technique. The effects of these inhibitors
      of nitric oxide synthesis were assessed on their ability to inhibit both the
      amplitude and the area of the vasodilator response. 2. The vasodilator responses
      evoked by low doses of 5-HT (5 x 10(-10)-10(-8) mol) were almost abolished by L
      NAME and L-NOARG (both at 10(-5), 3 x 10(-5) and 10(-4) M), although L-NOARG (3 x
      10(-5) M) was significantly less potent than L-NAME (3 x 10(-5) M) as an
      inhibitor of vasodilator responses to 5-HT (5 x 10(-8) mol). 3. The vasodilator
      responses evoked by substance P (5 x 10(-12)-5 x 10(-9) mol) were reduced in the
      presence of L-NAME and L-NOARG (both at 10(-5) and 3 x 10(-5) M). The response to
      substance P was almost abolished by L-NAME and L-NOARG (both at 10(-4) M). 4. The
      amplitude of the vasodilator responses to ATP (5 x 10(-11) and 5 x 10(-9)-5 x 10(
      7) mol) was little affected by either L-NAME or L-NOARG (both at 10(-5), 3 x 10(
      5) and 10(-4) M).7. It is concluded that in the guinea-pig coronary vasculature,
      the vasodilatation evoked by substance P and low doses of 5-HT is mediated almost
      exclusively via nitric oxide, whereas the vasodilatations evoked by ATP and
      bradykinin appear to involve other mechanisms in addition to the release of
      nitric oxide. L-NAME was a more effective agent than L-NOARG in inhibiting the
      vasodilator actions of 5-HT and ATP in this preparation.

PMID- 1384919
TI  - A 12-week placebo-controlled double-blind study of prazosin in the treatment of
      prostatic obstruction due to benign prostatic hyperplasia.
AB  - A series of 93 normotensive patients with benign prostatic hyperplasia and
      maximum urinary flow rates < 15 ml/s, treated at 2 hospital centres using an
      identical protocol, was randomly assigned to receive a 12-week course of
      treatment with prazosin or placebo in a double-blind parallel group trial. A
      total of 75 patients completed the study and were suitable for the final
      analysis. Prazosin was administered orally in doses of 0.5 mg and then 1 mg twice
      daily for 4 days and 2 mg twice daily for the remainder of the trial. Patients on
      treatment with prazosin exhibited a significantly increased maximum urinary flow
      rate as compared with placebo, with a significant reduction in maximum voiding
      detrusor pressure. Prazosin therapy did not produce a significant effect on
      either frequency or standard parameters of detrusor instability. A double-blind
      overall assessment of drug efficacy and tolerance significantly favoured prazosin
      therapy. A total of 30 patients receiving prazosin and 28 receiving placebo
      reported varied adverse effects. Eighteen patients were excluded from the final
      analysis, 10 being withdrawn because of adverse effects, 7 on treatment with
      prazosin and 3 in the placebo group. In long-term usage oral prazosin was well
      tolerated and appeared to improve obstructed voiding in patients with benign
      prostatic hyperplasia.

PMID- 1384920
TI  - Prostate specific antigen and bone scan correlation in the staging and monitoring
      of patients with prostatic cancer.
AB  - The ability of serum prostate specific antigen (PSA) to predict bone metastases
      at initial presentation was determined in 146 patients, and in 66 patients during
      a 3-year period; 14.7% of patients with bone metastases at presentation had a PSA
      value less than 20 ng/ml. All patients who subsequently developed bone metastases
      had a PSA greater than 20 ng/ml and the rise in PSA often antedated the detection
      of bone metastases. Bone scans are still necessary in the initial staging but
      following diagnosis and treatment can be replaced by serum PSA measurement in
      monitoring patients with prostatic cancer.

PMID- 1384921
TI  - Levels of prostate specific antigen that predict skeletal spread in prostate
      cancer.
AB  - The ability of serum prostate specific antigen (PSA) and serum acid phosphatase
      (SAP) to identify skeletal spread was evaluated in untreated patients with
      prostatic cancer. Twenty patients with scintigraphic evidence of metastatic
      disease in bone (M1) at diagnosis were compared with 50 untreated patients in
      whom scans were repeatedly negative during long-term surveillance. Using the
      present laboratory upper limit of normal (ULN) of 3 iu/l, the sensitivity and
      specificity of SAP for M1 disease were 80 and 86% respectively. Stepwise
      discriminant analysis demonstrated that SAP was able to stage patients correctly
      (bone scan positive or negative) with 81% predictive accuracy at an optimum cut
      off limit of 4.6 iu/l. By contrast, whilst PSA (Hybritech) was 100% sensitive for
      skeletal disease at 10 ng/ml--at the expense of poor (36%) specificity--analysis
      determined that an optimum cut-off limit of 58 ng/ml led to 79% predictive
      accuracy for disease in bone. It was concluded that PSA levels > 58 ng/ml are
      highly indicative of spread to the skeleton, even in the absence of radiological
      or scintigraphic evidence of metastases.

PMID- 1384922
TI  - Leukaemic infiltration, paracoccidioidomycosis and nodular hyperplasia of the
      prostate.

PMID- 1384923
TI  - Cytokines in tumour therapy.
AB  - Cytokines are low molecular weight proteins released by cells of the immune
      system that have therapeutic potential in cancer. They include the interleukins,
      the interferons, tumour necrosis factor and the colony-stimulating factors.
      Cytokines are capable of producing significant and sustained responses against a
      number of tumours. Clinically, the highest response rates to cytokine
      immunotherapy have been seen in melanoma and renal cell cancer. Current efforts
      aim to reduce treatment-related toxicity while maintaining the efficacy of
      cytokines. The therapeutic potential of these agents may be increased with
      genetic manipulation by introducing genes encoding cytokines into tumour
      infiltrating lymphocytes and certain tumour cells. However, immunotherapy remains
      time consuming and expensive, and further developments are necessary before it
      can have a definitive role in tumour management.

PMID- 1384924
TI  - The quantitative contribution of nitric oxide and sensory nerves to bradykinin
      induced inflammation in rat skin microvasculature.
AB  - Using a blister model in the rat hind footpad, the present study undertook to
      examine the relative contribution of sensory nerves and nitric oxide (NO) to the
      inflammatory response induced by bradykinin (BK). Using this model, combined with
      laser Doppler flowmetry, we were able to simultaneously monitor two parameters of
      the inflammatory response, namely vasodilatation (VD) and plasma extravasation
      (PE). Perfusion of BK (1, 10 or 100 microM) over the blister base elicited both
      VD and PE responses which were dose-dependent. The VD response was of rapid
      onset, sustained at the lowest concentration (1 microM), and showed tachyphylaxis
      at the highest two concentrations (10 and 100 microM). The PE response, however,
      was delayed in onset at the lower concentration but the response was maintained
      at all concentrations. The endothelium-independent vasodilator, sodium
      nitroprusside. (SNP, 100 microM), was used as an internal control and elicited a
      rapid maintained VD response. In rats pretreated as neonates with capsaicin to
      destroy primary sensory afferents, the inflammatory response to 10 microM BK was
      significantly smaller (50% and 64% decrease in VD and PE, respectively). The
      selective inhibitor of NO synthase, NG-nitro-L-arginine (L-NORAG) at 100 microM
      significantly attenuated the inflammatory response to BK in control rats (76% and
      60% decrease in VD and PE, respectively) with a further decrease in the response
      in capsaicin pretreated rats. The inactive stereoisomer NG-nitro-D-arginine (D
      NORAG) (100 microM) did not affect the inflammatory response to BK. The
      vasodilator response to SNP was intact in capsaicin pretreated rats and was not
      affected by either L-NORAG or D-NORAG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384925
TI  - Expression of the Purkinje cell specific zebrin antigens in the cerebellum of the
      meander tail mutant mouse.
AB  - The cerebellum of the meander tail mutant mouse is characterized by normal
      cytoarchitecture in the posterior lobe and agranular, abnormal cytoarchitecture
      in the anterior lobe. The Purkinje cells form a monolayer in the posterior lobe
      but are dispersed throughout the cortex of the anterior lobe. Examination of
      these cells with the zebrin antibodies demonstrates that in spite of the
      morphologic and laminar disorganization of these cells in the anterior lobe, they
      are organized into the appropriate number of correctly positioned immunopositive
      zebrin clusters.

PMID- 1384926
TI  - Anticonvulsive effects of galanin administered into the central nervous system
      upon the picrotoxin-kindled seizure syndrome in rats.
AB  - Galanin (2000, 1000 ng) administered into the lateral brain ventricle decreased
      the severity of picrotoxin-kindled convulsions in rats. The bilateral injection
      (200, 100 and 50 ng) of galanin into the hippocampus also evoked an
      anticonvulsive effect. When administered into the caudate nuclei or substantia
      nigra reticulata, galanin exerted anticonvulsive action only in a high dose (200
      ng), whereas in the nucleus accumbens it did so in a low dose (50 ng). When
      administered into the ventral tegmental area in a dose of 50, 100 or 200 ng
      galanin failed to reduce the manifestations of picrotoxin-kindled seizures.

PMID- 1384927
TI  - Mechanism of the galanin induced increase in acetylcholine release in vivo from
      striata of freely moving rats.
AB  - Galanin (GAL) administered intracerebroventricularly (i.c.v.) induced a strong
      and long-lasting increase in the basal acetylcholine (ACh) release from striata
      of freely moving rats only when the excitatory corticostriatal input was removed,
      while its effect was transient in striata of sham-operated rats. This effect was
      dose-dependent (0.78, 1.56 and 3.12 nmol) and was completely prevented by the GAL
      receptor antagonist, galantide. GAL injected locally (3.12 nmol) in deafferented
      striata also induced a persistent increase in ACh release although to a lower
      extent. The impairment of monoaminergic neurotransmission caused by alpha
      methylparatyrosine or p-chlorophenylalanine, respectively inhibitors of
      catecholamine and serotonin synthesis, completely prevented the rise in ACh
      output from deafferented striata while the muscarinic antagonist, scopolamine
      (0.5 mg/kg, s.c.), failed to do it. The data suggest that GAL in the deafferented
      striatum facilitates basal ACh release through an indirect mechanism. The effect
      seems to be at least partly mediated by an action of GAL on specific receptors in
      the striata.

PMID- 1384928
TI  - Galanin-like immunoreactivity in autonomic regions of the rat lumbosacral spinal
      cord is sexually dimorphic and varies with the estrous cycle.
AB  - These investigations show that there is a heterogeneous distribution of galanin
      like immunoreactivity (GAL-LI) within laminae VII and X of the rat thoraco-sacral
      spinal cord. In either sex, GAL-LI fibers sparsely outline the position of male
      and female preganglionic sympathetic neurons in thoracic spinal segments; whereas
      in lumbosacral segments, far greater numbers of GAL-LI fibers surround autonomic
      preganglionic neurons. An unusual feature of the GAL-LI fibers in lumbosacral
      autonomic regions is their sexually dimorphic distribution with males containing
      greater numbers of GAL-LI fibers than all females examined. In this regard,
      although the number of GAL-LI fibers observed in males was consistent from animal
      to animal, the amount of GAL-LI in females fell into two qualitative categories:
      an 'average' and a 'heavy' amount. These data indicate that the difference in the
      amount of GAL-LI in the female rat lumbosacral spinal cord is related to the
      estrous cycle, such that heavy amounts of GAL-LI are observed during proestrus
      and estrus, while average amounts of GAL-LI are associated with metestrus and
      diestrus.

PMID- 1384929
TI  - Physiological and pharmacological evidence for histamine as a neurotransmitter in
      the olfactory CNS of the spiny lobster.
AB  - Perfusing histamine (HA, 0.1 microM-1 mM) into the brain of the spiny lobster
      reversibly altered the spontaneous activity in 24 (86%) of 28 morphologically
      unidentified, odor-responsive interneurons. The effects of HA were dose-dependent
      and could be selectively and reversibly antagonized by cimetidine, a vertebrate
      H2 antagonist, suggesting that the action of HA in the central nervous system
      (CNS) was mediated by a receptor pharmacologically similar to an HA receptor
      expressed by lobster olfactory receptor cells. Perfusing HA into the brain also
      reversibly altered the spontaneous and/or odor-evoked activity of 6 (67%) of 9
      morphologically identified, odor responsive interneurons that arborized in the
      olfactory lobe (OL). These results extend previous evidence from our lab that the
      OL contains HA-immunoreactive interneurons and that OL tissue can synthesize HA
      from its precursor and further implicate HA as a putative neurotransmitter in the
      olfactory CNS of the spiny lobster.

PMID- 1384930
TI  - Testosterone regulates substance P within neurons of the medial nucleus of the
      amygdala, the bed nucleus of the stria terminalis and the medial preoptic area of
      the male golden hamster.
AB  - The medial nucleus of the amygdala, bed nucleus of the stria terminalis, and
      medial preoptic area appear to mediate steroidal regulation of mating behavior in
      male rodents. The mechanism of action has not been determined. One way
      testosterone could enhance neuronal function is by increasing neurotransmitter
      levels, thus altering neuronal transmission. To assess this hypothesis, we
      examined the effect of castration and testosterone treatment on substance P
      levels in the neurons of these three brain regions. Brains from male Syrian
      hamsters that were (1) gonadally intact, (2) castrated for 13 weeks, or (3)
      castrated for 9 weeks and treated with testosterone for 4 weeks, were processed
      for substance P, and the numbers of substance P immunoreactive neurons in the
      medial nucleus of the amygdala, bed nucleus of the stria terminalis, and medial
      preoptic area were determined. Castration reduced the number of substance P
      neurons in the bed nucleus of the stria terminalis and medial preoptic area
      relative to those in intact hamsters; the number of substance P neurons in these
      regions was restored by testosterone treatment. Castration did not reduce the
      number of substance P neurons in the medial nucleus of the amygdala; however,
      testosterone treatment increased the numbers of these neurons when compared to
      intacts. Thus, testosterone regulates substance P levels in areas that regulate
      mating behavior. As substance P enhances male copulatory behavior our results
      suggest that testosterone may regulate copulatory behavior by enhancing substance
      P levels in medial nucleus of the amygdala, bed nucleus of the stria terminalis
      and medial preoptic area.

PMID- 1384931
TI  - WGA-HRP and choleragenoid-HRP as anterogradely transported tracers in vagal
      visceral afferents and binding of WGA and choleragenoid to nodose ganglion
      neurons in rodents.
AB  - The axonal and terminal labelling pattern in the brain stem resulting from the
      injection of horseradish peroxidase (HRP) conjugate of wheat germ agglutinin
      (WGA) or choleragenoid into the nodose ganglion of guinea pigs was examined. In
      addition, the binding profiles of WGA and choleragenoid in the nodose ganglion of
      guinea pig and rat were examined. The results show that WGA-HRP and choleragenoid
      HRP (B-HRP) produce almost identical distribution of axonal and terminal
      labelling, the difference being some contralateral fibre labelling present only
      with B-HRP. However, WGA-HRP shows the strongest labelling at short survival
      times, whereas B-HRP requires longer postoperative survival times to reach
      maximum labelling intensity. All nodose ganglion neurons appear to bind WGA as
      well as choleragenoid although to a varying degree. The results of this and
      previous studies support the view that visceral sensory ganglion cells and the
      large light subpopulation of somatic dorsal root ganglion cells both bind
      choleragenoid, whereas the small dark somatic cells show affinity for WGA but
      rarely for choleragenoid.

PMID- 1384932
TI  - Species diversity of neuronectin and cytotactin expression patterns in the
      vertebrate central nervous system.
AB  - Two extracellular matrix proteins of brain tissue, neuronectin (NEC1) and
      cytotactin (CT), are disulfide-bonded multimers of M(r) 180,000-250,000 subunits.
      The previously known distribution of these molecules is, however, very different.
      Human NEC1 is found throughout the white matter of rostral segments of the adult
      central nervous system (CNS) but not in rostral gray matter or in caudal CNS
      segments, including the cerebellum. In contrast, CT is absent or expressed at a
      low level in the adult chicken cerebrum but highly expressed in the cerebellum.
      Despite these differences in distribution, results obtained with antibodies that
      recognize NEC1 and CT in several vertebrate species indicate that these molecules
      are identical or at least closely related: (1) alpha NEC1 antibodies recognize
      proteins affinity-purified with CT-binding proteoglycan; (2) proteins recognized
      by alpha NEC1 and alpha CT antibodies in cells constitutively expressing the
      molecules, cells in which expression is induced by growth factors and phorbol
      ester and cells treated with tunicamycin (to block glycosylation) are identical
      in subunit composition and mobility on SDS gels; (3) the removal of NEC1 from
      culture supernatants by immunoprecipitation removes all molecules reactive with
      alpha CT antibodies and vice versa; (4) immunoblots of brain extracts with alpha
      NEC1 and alpha CT antibodies yield identical results. Having demonstrated the
      structural similarity between NEC1 and CT, we reexamined their distribution in
      the CNS. Surprisingly, the temporal and spatial distribution pattern of NEC1/CT
      varied greatly among species. Immunohistochemical and immunoblot experiments with
      adult human CNS tissues revealed significant levels of NEC1/CT in rostral but not
      caudal segments. In contrast, in cows and pigs the molecule is found throughout
      the CNS. Adult rat and mouse brains show regionally restricted expression of
      NEC1/CT in several areas of the cerebrum--distinct from those showing NEC1/CT in
      the human--and in the molecular layer of the cerebellum. Tests with fetal and
      newborn tissues revealed that CNS development in humans, cows and pigs is not
      accompanied by the marked decline in NEC1/CT levels or the changes in subunit
      composition found in the chicken CNS. The marked species diversity in
      temporospatial expression patterns suggests that intrinsic and/or extrinsic
      elements controlling the expression of NEC1/CT have diverged during vertebrate
      evolution.

PMID- 1384933
TI  - Photoperiodic regulation of substance P immunoreactivity in the mating behavior
      pathway of the male golden hamster.
AB  - Mating behavior in the male golden hamster is regulated by both gonadal steroids
      and photoperiod. Gonadal steroids may regulate mating behavior by actions on the
      medial nucleus of the amygdala, bed nucleus of the stria terminalis, and medial
      preoptic area. Neurons in these areas actively accumulate gonadal steroids and
      lesions of these nuclei disrupt mating behavior in male hamsters. Photoperiodic
      regulation of mating behavior is regulated, at least in part, by decreased
      responsiveness to gonadal steroids. Therefore, we sought to determine if the
      changes induced by changes in gonadal steroids would mimic those induced by
      changes in photoperiod. The number of substance P-containing neurons in these
      areas decrease following castration and are restored with testosterone treatment
      suggesting that this peptide may mediate steroidal regulation of male mating
      behavior. To determine the effect of photoperiod on substance P, peptide
      containing neurons were counted in (1) enucleates (n = 6), (2) enucleated
      castrates treated with testosterone (n = 6), (3) castrates treated with
      testosterone (n = 4), and (4) intact controls (n = 6). Bilateral enucleation
      caused a decrease in the number of substance P neurons in the medial nucleus, bed
      nucleus of the stria terminalis, and medial preoptic area (P less than 0.05).
      Testosterone treatment prevented this decrease (P less than 0.05). Thus, a
      decrease in daylength causes a decrease in substance P in the medial nucleus of
      the amygdala, the medial bed nucleus of the stria terminalis and the medial
      preoptic area that is mediated by changes in testosterone levels.

PMID- 1384934
TI  - Prenatal ontogeny of substance P-like immunoreactivity in the parabrachial
      nucleus of the human fetus--an immunocytochemical study.
AB  - Using an immunocytochemical method, the prenatal ontogeny of substance P-like
      immunoreactivity (SP-LI) was demonstrated in the parabrachial nucleus (PB) of
      human fetus, fetal age (menstruation age) 11.5 to 40 weeks. The time of initial
      appearance of SP-LI in the human brainstem PB was between fetal age 11.5 weeks
      and 16 weeks. While the fetus grew, the density of SP-LI fibers and terminals in
      the human fetus brainstem PB increased constantly from fetal age 16 weeks to 40
      weeks. These findings indicate that substance P (SP) might play an important role
      in the human parabrachial nucleus development and in its functional establishment
      during the prenatal period.

PMID- 1384935
TI  - Effects of benzylpiperazine derivatives on the neurotoxicity of 3,4
      methylenedioxymethamphetamine in rat brain.
AB  - The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) in rat brain was
      attenuated significantly by coadministration of several benzylpiperazines (p
      nitrobenzylpiperazine, p-chlorobenzylpiperazine and 1-piperonylpiperazine), which
      were weak inhibitors for [3H]6-nitroquipazine binding to the 5-hydroxytryptamine
      (5-HT) transporter in rat brain. These results suggest that these
      benzylpiperazines may inhibit the MDMA-induced neurotoxicity by a novel
      neuropharmacological effect other than 5-HT uptake inhibition.

PMID- 1384936
TI  - Trigeminal and dorsal column nuclei projections to the anterior pretectal nucleus
      in the rat.
AB  - The projections of the trigeminal (V) sensory nuclei (VSN) and the dorsal column
      nuclei (DCN) to the anterior pretectal nucleus (APT) of the rat were investigated
      by the use of anterograde and retrograde transport of wheat-germ agglutinin
      conjugated horseradish peroxidase (WGA-HRP). Injections of WGA-HRP into the APT
      retrogradely labeled neurons in the contralateral VSN and DCN. The labeled
      neurons in the VSN were most concentrated in the rostral V subnucleus
      interpolaris (Vi), but were also found in caudal V subnucleus oralis (Vo). No
      labeled neurons were seen in V subnucleus caudalis. In the DCN, retrogradely
      labeled neurons were observed in rostral portions of both the cuneate (Cu) and
      gracile (Gr) nuclei. Injections of WGA-HRP into the rostral Vi or caudal Vo
      resulted in dense anterograde terminal labeling in the ventral two-thirds of the
      APT; the labeling was maximal in the ventromedial part of the caudal half of the
      APT and did not extend into its most rostral portion. Labeling resulting from
      injections of tracer into Cu or Gr was located primarily in the ventral half of
      the APT, was maximal in the mid-levels of the nucleus and extended into its
      rostral portions. These results indicate the existence of prominent somatosensory
      projections to the APT and are consistent with recent findings suggesting a role
      for the APT in sensorimotor integration.

PMID- 1384937
TI  - Reduction of blood PO2 decrease and PCO2 increase during asphyxia by paramedian
      reticular nucleus in cats.
AB  - Effects of activation of paramedian reticular nucleus (PRN) on the systemic
      arterial blood pressure (SAP), heart rate, renal nerve activity (RNA), and
      changes of the partial pressure of the arterial blood oxygen (PO2) and carbon
      dioxide (PCO2) during asphyxia were studied in cats anesthetized with chloralose
      (40 mg/kg) and urethane (400 mg/kg). During a 35-s period of asphyxial anoxia,
      SAP and RNA increased while heart rate decreased significantly. The arterial
      blood PO2 decreased by 64.6 +/- 4.7% while the PCO2 increased by 54.6 +/- 6.3%.
      Electrical stimulation of PRN produced a mild to moderate decrease of the SAP,
      heart rate, and RNA, but arterial PO2 and PCO2 did not change significantly. When
      PRN was stimulated simultaneously with asphyxia, increases of SAP and RNA and
      changes of blood gases subsequent to asphyxia reduced significantly. Arterial PO2
      decreased only 54.0 +/- 4.9% while the PCO2 increased 39.4 +/- 10.5% (p < 0.01).
      Similar effects were observed in the venous blood from inferior vena cava. In
      addition, when the arteriovenous difference of PO2 and PCO2 was compared,
      simultaneous PRN stimulation during asphyxia produced a higher PO2 reserve
      (66.3%) and less PCO2 production (-7%) than without PRN stimulation; PO2 54.2%,
      PCO2 (-2.9%). The results suggest that PRN is a structure that can exert
      inhibition over a wide spectrum of body functions; not only autonomic system but
      probably also metabolism.

PMID- 1384938
TI  - A new, simple myelin stain.
AB  - A new and convenient myelin stain is described. Paraformaldehyde fixed tissue is
      serially immersed in a nitroblue tetrazolium solution and then in a
      diaminobenzidine solution. The result is distinct blue staining of myelinated
      fiber tracts. This technique has advantages over presently used myelin stains.

PMID- 1384939
TI  - [Congenital indifference and congenital insensitivity to pain].
AB  - Congenital indifference to pain is often mistaken for congenital insensitivity.
      It is characterized by the occurrence since childhood of lesions, mainly
      cutaneous and osteoarticular secondary to strictly painless traumas. However,
      despite the lack of pain, the patient is able to discriminate a painful stimulus.
      Autopsy shows no abnormality of the nervous system. A dysfunction of the central
      endomorphinic systems has been suggested. Congenital analgesia is associated with
      anhidrosis in Swanson's syndrome (in which Lissauer the tractus is absent in the
      spinal cord) and with dysautonomia in Riley-Days's disease (in which there is a
      lack of amyelicinic fibres). On account of these data, some authors refuse the
      autonomy of congenital indifference and classify it in the group of the various
      autonomic and sensory neuropathies. However it seems justified to acknowledge the
      congenital analgesia with two varieties: congenital indifference in which there
      is no sensation of pain but normal sensory pathway and tonic function of
      endomorphinic system, congenital insensitivity in which the painful stimulus is
      not transmitted to the central nervous system.

PMID- 1384940
TI  - Alpha-fetoprotein synthesis in human hepatocellular carcinoma: correlation with
      hepatitis B surface antigen expression.
AB  - We analyzed the pattern of alpha-fetoprotein (AFP) synthesis in 40 consecutive
      human hepatocarcinomas (HCC) in relation to hepatitis B viral (HBV) infection. In
      addition, histopathological characteristics of liver parenchyma and the tumor
      itself were examined. Elevated AFP (> 20 ng/ml) were found in 90% of HCC patients
      and in none of the controls. In 35% of HCC cases, serum AFP was above 100,000
      ng/ml. AFP levels were significantly higher in patients seropositive for
      hepatitis B surface antigen (HBsAg) compared with their negative counterparts
      (mean log[AFP]: 4.28 +/- 1.67 vs. 3.28 +/- 1.96, respectively; geometric mean
      (GM): 19,322.6 ng/ml and 1939.5 ng/ml, respectively; p < 0.05). Furthermore,
      serum AFP levels were higher in HCC patients with liver cirrhosis than in those
      without (log[AFP]: 4.43 +/- 1.58 vs. 3.23 +/- 1.98, respectively; p < 0.05).
      However, the relationship of cirrhosis with AFP was confounded by the high
      prevalence of HBsAg in cirrhotic HCC patients. There was no correlation of AFP
      with either liver necrosis (abnormal AFP in 45% of cases; mean log[AFP]: 3.99 +/-
      1.91 vs. 3.75 +/- 1.85 for HCC with and without necrosis, respectively; 0.05 < p
      < 0.68, not significant (NS)), or inflammation (abnormal AFP in 25%; mean
      log[AFP]: 4.33 +/- 1.62 vs. 3.70 +/- 1.93 for HCC with and without inflammation,
      respectively; 0.05 < p < 0.39, NS). A vast majority of HCC (75%) were moderately
      (grade 2-3) or poorly differentiated tumors (grade 3, grade 4, or combined grade
      3-4). Serum AFP did not correlate with tumor grade. Immunohistochemical analysis
      of HBsAg and AFP confirmed the serological findings, and confirmed earlier
      observations of elevated AFP in HBsAg-positive patients. These results may
      reflect pathogenic and biological differences between HBsAG-secreting and
      nonsecreting HCC.

PMID- 1384941
TI  - Neuronal and glial glutamate-receptor channels in the cerebellum.

PMID- 1384942
TI  - [Total chemical synthesis of natural transfer RNA].
AB  - New improvements in the chemical synthesis of oligoribonucleotides are reported
      and they are applied to the first total chemical synthesis of a natural RNA. This
      E. coli K12 alanine tRNA contains in its sequence dihydrouridine, ribothymidine
      and pseudo-uridine. The synthetic tRNA was fully sequenced and showed a 42%
      aminoacyl acceptance activity. When tRNA was used as a template, reverse
      transcriptase directed the incorporation of adenine opposite dihydrouridine,
      ribothymidine and pseudouridine.

PMID- 1384943
TI  - Expression of developmentally relevant proteins by rodent embryo CNS cells in
      vivo and in vitro: proto-oncogene pp60c-src and high molecular weight
      neurofilament protein.
AB  - The expression of proteins that play a role in neuronal differentiation was
      examined in central nervous system (CNS) micromass embryo cell cultures and
      compared to expression at comparable developmental stages in vivo. The protein
      product of the src proto-oncogene (pp60c-src) has been postulated to have a
      specific role in development because, although it is expressed in many tissues,
      marked increases in amount and activity of pp60c-src occur in neurons at the time
      of differentiation. Another protein of interest, high molecular weight
      neurofilament (NF) protein, is found in differentiated neurons. In the present
      study, changes over time in the expression of these two proteins in vitro and in
      vivo were examined. In the micromass cell cultures, primary cells from day 12 rat
      embryo CNS are plated at high density and differentiate into neurons during five
      days in culture. Tissues from embryos grown in vivo were assessed at 12 and 17
      days post-coitum. Proteins were quantified by PAGE separation of equal amounts of
      total protein followed by transfer to membranes, immunoblotting, and
      densitometric scanning of blots. Increases in the amount of both proteins with
      neuronal differentiation was shown. Protein kinase activity of immunoprecipitated
      pp60c-src also increased in cell cultures and in embryos. Similarity in patterns
      of expression between in vitro and in vivo tissue samples provides further
      evidence that the cultures closely simulate in vivo differentiation and are a
      useful system for examining expression of developmental genes in vitro.

PMID- 1384944
TI  - Relaxant effects on iloprost in canine cerebral artery.
AB  - Iloprost caused relaxation of rings of canine cerebral arteries precontracted
      with prostaglandin F2 alpha or the thromboxane A2 analogue U46619, but it was
      without effect on arteries precontracted with potassium chloride. Pretreatment
      with iloprost did not significantly affect the concentration-response curve to
      any agent. Contractile responses to oxyhemoglobin were completed relaxed by
      iloprost. In arteries from animals with moderate cerebrovascular spasm, the
      response to prostaglandin F2 alpha was also reduced by iloprost. The observation
      that iloprost relaxes the response to oxyhemoglobin to prostaglandin F2 alpha in
      spastic arteries may be of interest in the management of cerebral vasospasm.

PMID- 1384946
TI  - The indirect negative inotropic effects of the P1-receptor agonist, L
      phenylisopropyladenosine, in guinea-pig isolated cardiac preparations: comparison
      with cromakalim.
AB  - The possible mechanisms of the indirect negative inotropic responses to the P1
      receptor agonist, L-phenylisopropyladenosine (L-PIA) were evaluated in
      electrically paced (2 Hz, 5 ms pulse width, voltage 50% above threshold) left
      atria and papillary muscles of guinea pigs. The responses were compared in naive
      tissues (direct effects) or after prestimulation with submaximal concentrations
      of either cAMP-dependent positive inotropes (isoprenaline or forskolin) or the
      cAMP-independent inotrope Bay K 8644. Cumulative concentration-response curves
      were obtained in naive or prestimulated preparations for L-PIA or the potassium
      channel activator, cromakalim, for comparison. L-PIA and cromakalim exerted
      negative inotropy in naive atrial tissues, whereas only cromakalim was active in
      naive papillary muscles. In atria prestimulated with isoprenaline (31 nM) or
      forskolin (1.4 microM), the negative inotropy of L-PIA was enhanced compared with
      naive tissues. In contrast, prestimulation with Bay K 8644 (1 microM) exerted a
      significant functional antagonism of the response to L-PIA. In the case of
      cromakalim, prestimulation with isoprenaline exerted a functional antagonistic
      effect. In papillary muscles, an indirect negative inotropic effect of L-PIA was
      only seen in tissues prestimulated with the cAMP-dependent inotropes isoprenaline
      (31 nM) or forskolin (2.4 microM), and not in naive tissues or those
      prestimulated by Bay K 8644 (333 nM). As with atria, prestimulation with
      isoprenaline exerted a functional antagonistic effect on the response to
      cromakalim. These results suggest that the P1-receptor agonist, L-PIA, exerts its
      indirect negative inotropic effects in left atria by two mechanisms.2+ with cAMP
      dependent positive inotropes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1384947
TI  - Neurological findings in HIV-infected children: a review of 49 cases.
AB  - Many HIV-infected children have neurological involvement. We present our
      observations in 49 cases, 58% of which had some form of clinical neurological
      impairment. Most of the patients affected (71%) presented with progressive
      encephalopathy, characterized by developmental delay with loss of acquisitions
      and cognitive decline, an impaired growth curve, microcephaly and corticospinal
      dysfunction. CT-scan imaging shows cerebral atrophy in all cases and basal
      ganglia calcifications in 29%. Non-specific abnormalities are found on the EEG in
      two-thirds of cases and in the CSF in slightly less than half the cases.
      Pathological studies sometime revealed HIV encephalitis or lateral corticospinal
      tracts degeneration. Neurological impairment secondary to vascular events,
      neoplasms or opportunistic infections were rare, especially when compared with
      the adult HIV population.

PMID- 1384945
TI  - Renorenal reflexes: interaction between efferent and afferent renal nerve
      activity.
AB  - In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure
      results in a contralateral inhibitory renorenal reflex response consisting of
      increases in ipsilateral afferent renal nerve activity, decreases in
      contralateral efferent renal nerve activity, and increases in contralateral urine
      flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To
      study possible functional central interaction among the afferent renal nerves and
      the aortic and carotid sinus nerves, the responses to renal mechanoreceptor
      stimulation were compared in sinoaortic denervated rats and sham-denervated rats
      before and after vagotomy. In contrast to sham-denervated rats, there was an
      increase in mean arterial pressure in response to renal mechanoreceptor
      stimulation in sinoaortic-denervated rats. However, there were no differences in
      the renorenal reflex responses among the groups. Thus, our data failed to support
      a functional central interaction among the renal, carotid sinus, and aortic
      afferent nerves in the renorenal reflex response to renal mechanoreceptor
      stimulation. Studies to examine peripheral interaction between efferent and
      afferent renal nerves showed that marked reduction in efferent renal nerve
      activity produced by spinal cord section at T6, ganglionic blockade, volume
      expansion, or stretch of the junction of superior vena cava and right atrium
      abolished the responses in afferent renal nerve activity and contralateral renal
      function to renal mechanoreceptor stimulation. Conversely, increases in efferent
      renal nerve activity caused by thermal cutaneous stimulation increased basal
      afferent renal nerve activity and its responses to renal mechanoreceptor
      stimulation. These data suggest a facilitatory role of efferent renal nerves on
      renal sensory receptors.

PMID- 1384948
TI  - Immunophenotyping of subtypes of B-chronic (mature) lymphoid leukemia. A study of
      242 cases.
AB  - BACKGROUND: The French-American-British group's proposal for the classification
      of chronic lymphoid leukemias is unique at this time. Testing, expanding, and
      adding to the theory by immunophenotyping will help to additionally characterize
      this group of diseases. METHODS: Peripheral blood samples from 242 patients with
      chronic lymphoid leukemias were analyzed for immunologic evaluation of the
      following subtypes: typical chronic lymphocytic leukemia (CLL), 189; CLL with
      pleomorphic lymphocytes (CLL-pleo), 19; CLL of mixed cell type (CLL/PL), 20;
      prolymphocytic leukemia (PLL), 22; hairy cell leukemia (HCL), 10; HCL-variant, 1;
      and splenic lymphoma with villous lymphocytes, 1. RESULTS: The phenotype of CLL
      and CLL-pleo was weak surface immunoglobulin (SIg) with positive results of mouse
      rosettes (MR+), CD5+, and CD22-. Of PLL and HCL, it was strong SIg, MR-, CD5-,
      and CD22+. By analyzing the four markers and accepting the relevant results of
      two or more as sufficient for diagnosis, all cases (100%) of CLL, CLL-pleo, PLL,
      and HCL were diagnosed. CLL/PL showed the phenotype of CLL in 66.67% and of PLL
      in 33.33% of patients. The frequency of cases with weak fluorescence in
      decreasing order was CLL, CLL-pleo, CLL/PL, and PLL and HCL. The same sequence
      applied to the mean percentage of mouse rosette-forming cells and CD5 cells, but
      the sequence was reversed for CD22 cells. CONCLUSIONS: SIg intensity, MR, CD5,
      and CD22 constitute the minimum number of immune markers for the differential
      diagnosis of the subtypes of chronic lymphoid leukemia. The frequency of the four
      markers among the subtypes suggested that CLL and CLL-pleo have identical
      phenotypes and that the five subtypes follow a continuous range of B-cell
      differentiation from early mature (CLL and CLL-pleo) to late mature pre-plasma
      cell stages (PLL followed by HCL), with CLL/PL of intermediate maturity.

PMID- 1384949
TI  - Comparison of psychosocial adaptation and sexual function of survivors of
      advanced Hodgkin disease treated by MOPP, ABVD, or MOPP alternating with ABVD.
AB  - BACKGROUND: Survivors of advanced Hodgkin disease, who were assigned randomly to
      treatment by mechlorethamine, vincristine, procarbazine, and prednisone (MOPP);
      doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); or MOPP alternating
      with ABVD in a clinical trial of the Cancer and Leukemia Group B (protocol 8251),
      were compared in terms of their psychosocial adaptation and psychosexual function
      an average of 2.2 years after completion of treatment (range, 1-5 years). The
      study was undertaken to determine if there were differences among treatments in
      these functional areas as a consequence of differential long-term gonadal damage
      in the three regimens. METHODS: Ninety-three disease-free survivors of advanced
      Hodgkin disease (56 men and 37 women) were studied (a minimum of 1 year after
      completion of treatment) by an interview conducted over the telephone.
      Standardized measures were used to assess their psychologic, sexual, family, and
      vocational functioning, including the following tests: the Psychosocial
      Adjustment to Illness Scale--Self Report, the Brief Symptom Inventory, the
      Profile of Mood States, and the Impact of Event Scale. RESULTS: Contrary to
      expectation, no statistically significant differences in survivors' psychosocial
      adaptation or psychosexual function were found by treatment arm. Infertility
      (based on survivors' reports of medical test results and perceptions) and lower
      income 1 year before the diagnosis of cancer were significant predictors of
      poorer adjustment. Most survivors reported a range of problems that they
      attributed to having had cancer: 35%, proven or perceived infertility; 24%,
      sexual problems; 31%, health and life insurance problems; 26%, a negative
      socioeconomic effect; and 51%, conditioned nausea, associated with visual or
      olfactory reminders of chemotherapy. CONCLUSIONS: No significant long-term
      advantage in psychosocial adaptation or psychosexual function was found for
      survivors of Hodgkin disease treated by the less gonadally toxic ABVD regimen 1
      to 5 years after completion of treatment.

PMID- 1384950
TI  - Specific expression of the ras-related rab3A gene in human normal and malignant
      neuroendocrine cells.
AB  - BACKGROUND: The authors originally demonstrated the tissue-specific expression of
      the rab3A gene in the mouse brain. In the current study, they analyze the
      activity of this gene in fresh human tumors associated with neuronal phenotype
      compared with normal and malignant cells from other origins. METHODS: The authors
      studied the transcription levels of the rab3A gene by Northern blot in 81 fresh
      tumors. RESULTS: A high rab3A gene expression was observed in tumor samples
      derived from the neural tube (i.e., neuroblastomas, ganglioneuroblastomas, and
      adult nervous system neoplasms). In addition, this tissue-specific expression
      extended to neuroendocrine tumors of the gut, small cell lung cancers, and
      pheochromocytomas. CONCLUSIONS: These results suggest a specific restriction
      pattern to human cells derived from the neural tube and neural crests. The
      GTP/GDP-binding rab3A protein may be a useful differentiation marker of neuro
      endocrine cells in the characterization of undifferentiated neoplasms.

PMID- 1384951
TI  - Treatment of childhood germ cell tumors. Review of the St. Jude experience from
      1979 to 1988.
AB  - BACKGROUND: The outlook for patients with germ cell tumors was poor before the
      advent of effective chemotherapy. The authors assessed the outcome of treatment
      with multiagent chemotherapy (with or without radiation therapy) in children
      treated for germ cell tumors at St. Jude Children's Research Hospital (SJCRH).
      METHODS: Sixty children with germ cell tumors were treated between January 1979
      and June 1988. Postsurgical treatment was based on tumor site, stage, and
      histology. Most patients received chemotherapy with vincristine, actinomycin-D,
      and cyclophosphamide (VAC), or a modified Einhorn regimen (cisplatin, bleomycin,
      and vinblastine [PVB]); in the absence of response to initial therapy, patients
      received alternating courses of VAC and PVB (VAC/PVB regimen). Exceptions were
      patients with Stage I testicular tumors (observation only) and ovarian germinomas
      (Stage I tumors measuring less than 10 cm, observation only; tumors larger than
      10 cm or Stage II-III disease, radiation only; and Stage IV disease, VAC plus
      radiation). RESULTS: The estimated 5-year survival is 100% for patients with
      Stage I disease (n = 18), 87% for patients with Stage II (n = 8), 72% for Stage
      III (n = 25), and 56% for Stage IV (n = 9). Patients with testicular tumors of
      any stage or with Stage I-II ovarian tumors had 100% 5-year survival.
      Extragonadal tumors responded poorly to VAC alone with recurrent or progressive
      disease in eight of nine patients. Treatment for those tumors was changed to
      alternating courses of VAC and PVB, which failed in only one of seven patients.
      Nine of 19 patients with advanced ovarian tumors had disease recurrence with VAC;
      these patients then received PVB, which was effective in four cases. CONCLUSIONS:
      For patients with advanced germ cell cancers, intensification of therapy or the
      development of new approaches is necessary. In contrast, future trials in
      children with limited stage should focus on reducing acute and long-term
      toxicities.

PMID- 1384952
TI  - Acute arterial thrombosis after escalated-dose methotrexate, vinblastine,
      doxorubicin, and cisplatin chemotherapy with recombinant granulocyte colony
      stimulating factor. A possible new recombinant granulocyte colony-stimulating
      factor toxicity.
AB  - Combination chemotherapy with a regimen of methotrexate, vinblastine,
      doxorubicin, and cisplatin (M-VAC) has produced long-term survival times in a
      significant proportion of patients with advanced nodal and metastatic urothelial
      tumors. The availability of the colony-stimulating factors has spurred interest
      in studies evaluating escalated dosing schedules of M-VAC in an attempt to
      improve major response rates and overall survival. More frequent use of the
      colony-stimulating factors, however, in this and other settings may be associated
      with unrecognized side effects. The authors report a case of arterial thrombosis
      in a 69-year-old man receiving recombinant granulocyte colony-stimulating factor
      (rhG-CSF) and escalated-dose M-VAC for treatment of a transitional cell carcinoma
      of the bladder. Incidents of venous thrombosis have been reported previously with
      the use of colony-stimulating factors, but, to the knowledge of the authors, this
      case represents the first report of an arterial thrombosis occurring in a patient
      receiving rhG-CSF.

PMID- 1384953
TI  - Estradiol- and estriol-binding in human benign prostatic hyperplasia.
AB  - Binding of the natural estrogens, estradiol and estriol, was investigated, in 34
      samples of human benign prostatic hypertrophy (BPH) tissue, using Scatchard
      analysis and agar gel electrophoresis. Saturation binding analysis using a wide
      range of concentrations of both ligands resulted in curvilinear Scatchard plots.
      This confirmed the presence of two binding forms for estradiol: a true estrogen
      receptor, and a protein with lower affinity and higher capacity. Both binding
      species were also demonstrated and quantified with estriol. The electrophoretic
      process, after incubation at low and high ligand concentrations also resulted in
      separation, for both estrogens, of two binding peaks. They are probably two
      distinct forms of the low affinity, high capacity binding measured by Scatchard.
      The procedure used in our laboratory was not able to provide accurate
      determination of the concentrations of these binding forms. Possible
      modifications to alleviate these drawbacks are discussed.

PMID- 1384954
TI  - Expression of c-kit receptor in normal and transformed human nonlymphoid tissues.
AB  - The protooncogene c-kit encodes a tyrosine kinase with a molecular weight of
      145,000, highly related to the platelet derived growth factor/colony stimulating
      factor receptors. Mutations of the murine gene result in impairment of
      hematopoiesis, gametogenesis, and of the melanocyte cell lineage. In order to
      elucidate c-kit functions in development and oncogenesis we have analyzed
      immunohistochemically its expression in human normal and transformed nonlymphoid
      tissues. The receptor has been detected in spermatogonia, melanocytes, and
      unexpectedly, in astrocytes, renal tubules, parotid cells, thyrocytes, and breast
      epithelium. While the gene product is expressed in seminoma, lung tumors, and
      melanoma of low invasiveness, no detectable levels have been detected in thyroid
      and breast carcinomas, astrocytomas, and invasive melanomas. In breast tumors
      these findings were confirmed by paired, Northern blot analysis of RNA
      preparations from normal and transformed tissue. The present results demonstrate
      that the c-kit receptor plays a role in the development of a larger spectrum of
      cell lineages. Furthermore, on the basis of the transformation associated
      changes, we speculate that, while in some cell types, c-kit expression positively
      regulates mitogenesis and is selected for in neoplastic transformation, in other
      tissues the c-kit pathway is involved in morphogenesis and differentiation and
      is, therefore, negatively selected in the course of tumor progression.

PMID- 1384955
TI  - Retinoid status and the control of keratin expression and adhesion during the
      histogenesis of squamous metaplasia of tracheal epithelium.
AB  - We induced vitamin A depletion to define early and late changes during the
      histogenesis of squamous metaplasia of hamster tracheal epithelium. An early
      change is the "minimal morphological change" (MMC), in which the mucociliary
      epithelium is separated from the basement membrane by a continuous layer of basal
      cells. Immunohistochemistry showed an exclusive localization of the keratins K5
      and K14 in basal cells of normal and MMC epithelia. At the MMC stage no staining
      was observed above the basal layer with antibodies to K5, but upon progression of
      the lesion to a squamous focus all cells from basal to terminally differentiated
      were positive for K5 and K14. In contrast, when we used antibodies to the
      keratins K6 or K13 all cells were negative in the normal epithelium and in the
      MMC epithelium. Successive layers of suprabasal squamous cells found in squamous
      metaplasia failed to express normal epidermal differentiation marker keratins K1
      and K10 but expressed the proliferation marker keratin K6 and the internal
      stratified epithelium keratin K13, not normally found in the epidermis or in the
      trachea. Hamster tracheal epithelial cells could be maintained in culture in
      serum-free medium for at least 4 weeks in the presence of retinoic acid (RA). In
      non-RA-containing medium, cells from vitamin A-deficient hamsters showed markedly
      reduced growth and an increase in the expression of keratins K5, K6, K13, and
      K14. Since our previous work had implicated retinoids in the control of cell
      adhesiveness, we were interested to find out whether changes in cell adhesion
      occur in vitamin A-deficient hamster tracheal epithelial cells, compared to
      normal cells. Functional assays demonstrated that hamster tracheal epithelial
      cells, obtained from non-RA-treated tracheas or maintained in culture, displayed
      reduced attachment to laminin, compared to RA-treated cells. Immunofluorescence
      studies did not show a decrease either in the alpha 6 integrin subunit, which was
      localized in the basal aspect of basal cells, or in basement membrane laminin.
      However, the expression of laminin-binding protein 37 decreased as the epithelium
      changed from pseudostratified to stratified. Therefore, a coordinated pattern of
      changes in keratin gene expression, as well as in the expression of laminin
      binding protein 37, the precursor to the cell surface laminin receptor 67LR, and
      in adhesive properties takes place in tracheal epithelium when its phenotype
      changes from mucociliary to the preneoplastic stage of squamous metaplasia.

PMID- 1384956
TI  - Complementary DNA cloning for galactosyltransferase associated with tumor and
      determination of antigenic epitopes recognized by specific monoclonal antibodies.
AB  - The galactosyltransferase associated with tumor (GAT) was the name given to the
      isoenzyme that tends to polymerize resulting in slower moving in a nondenaturing
      polyacrylamide gel electrophoresis than normal (beta 1-4)galactosyltransferase
      (normal GalT). A complementary DNA (cDNA) library was constructed from a human
      ovarian cancer cell line, RMG-I, which secreted an amount of GAT into the culture
      supernatant and screened with monoclonal antibodies (MAbs) against GAT and normal
      GalT. One of six cDNA clones, UG86-1, encoded an epitope recognized by a GAT
      specific MAb, 8513. Recombinant proteins expressed by UG86-1 in Escherichia coli
      also had antigenic epitopes recognized by the other MAbs against normal GalT. The
      229-base pair nucleotide sequence encoded by UG86-1 was identical to the stem
      region sequence of HGT832 which encodes a full-length cDNA of human GalT. Using
      recombinant proteins directed by deletion mutant cDNAs, the antigenic epitopes
      recognized by each MAb were determined. The epitope of MAb8628, which reacts to
      both the GAT and normal GalT, was localized to the COOH-terminal side of
      proteolytic cleavage site where the membrane-bound form enzyme is cleaved to be
      converted to soluble forms, while MAb8513 epitope was at the NH2-terminal side
      from this cleavage site between the COOH-terminal end of the membrane-binding
      domain and the cleavage site. These results demonstrate that GAT is produced by
      aberrant proteolytic cleavage at the different site, closer to the membrane
      binding domain, from the normal GalT.

PMID- 1384957
TI  - Colocalization of basal and luminal cell-type cytokeratins in human prostate
      cancer.
AB  - In the epithelium of secretory acini of the prostate two different cell types can
      be discriminated on the basis of localization, morphology, and degree of
      differentiation, the luminal and basal cells. The possibility of a developmental
      relationship between basal and luminal cells has been a subject of interest in
      several studies. According to the stem cell model at least three cell types,
      i.e., stem, amplifying, and transit cells, can be discriminated in the epithelium
      of prostate secretory acini. We previously reported that in the process of
      degeneration and regeneration in normal rat prostate a population of cells could
      be identified as candidates for the amplifying cells. These cells showed a
      keratin expression profile intermediate between those of basal and luminal cells.
      We now show, by using keratin antibodies, that also in normal human prostate at
      least three subpopulations of cells can be identified, one of them putatively
      representing amplifying cells as defined in the stem cell model. Furthermore,
      these antibodies were used to obtain a better insight into the different cell
      types involved in the etiology and progression of prostatic carcinoma. Both
      primary and hormone-independent prostatic tumors were investigated. Our results
      indicated that the candidate stem cell population was absent in prostatic
      carcinoma. Unlike earlier reports on the unique presence of cells with luminal
      characteristics in prostatic carcinoma, we identified also a population of cells
      coexpressing basal and luminal cell-type cytokeratins in primary and hormone
      independent prostatic carcinoma. Since amplifying cells are defined in the stem
      cell model as precursors of transit (luminal) cells in the hierarchical pathway
      of prostatic epithelium differentiation, we postulate that on the basis of the
      keratin expression profile this subpopulation is most likely the target for
      neoplastic transformation.

PMID- 1384958
TI  - Prolonged survival of thymoma-bearing mice after vaccination with a soluble
      protein antigen entrapped in liposomes: a model study.
AB  - EG7-OVA cells are mouse thymoma EL4 cells stably transfected with the
      complementary DNA of chicken ovalbumin (OVA) and thus express OVA epitopes as a
      unique antigen. Cytotoxic T lymphocytes specific to OVA can be elicited by
      immunization of mice with OVA osmotically loaded into syngeneic splenocytes or
      entrapped in liposomes. Cytotoxic T lymphocytes thus induced can specifically
      cytolyse the EG7-OVA cells in vitro in an antigen-specific and major
      histocompatibility complex-restricted manner. In the present study, we have
      examined in this model system whether immunization with liposomal OVA can protect
      mice against tumors induced by EG7-OVA cells. Vaccination with OVA either
      entrapped in liposomes or osmotically loaded in the syngeneic splenocytes
      prolonged the survival of mice which had been challenged with EG7-OVA cells, but
      not those mice challenged with the parent EL4 cells. The antitumor effect was
      attributed to the induced OVA-specific cytotoxic T lymphocyte activity, since
      other forms of acquired immunity such as interaction of tumor cells with specific
      antibody could not be detected. Our results demonstrate that immunization with
      antigen incorporated in liposomes could be a useful means of inducing a
      protective antitumor response.

PMID- 1384959
TI  - Identification of a novel CD56- lymphokine-activated killer cell precursor in
      cancer patients receiving recombinant interleukin 2.
AB  - Circulating lymphokine-activated killer (LAK) cell activity in cancer patients
      receiving recombinant interleukin 2 (rIL-2) therapy is confined to cells
      expressing the CD56- surface marker. However, CD56- cells from these patients but
      not normal individuals have been reported to exhibit LAK cytotoxicity only
      following in vitro activation with rIL-2. Studies were performed to document the
      existence of CD56- LAK precursor cells and to phenotypically characterize this
      population in patients receiving rIL-2 therapy using fluorescence-activated cell
      sorter-purified CD56- cell subsets. Initial studies confirmed that CD56- cells
      exhibit NK activity [20 +/- 7 (SE) LU/10(6) cells] but not LAK activity (0 +/- 0
      LU/10(6) cells) when evaluated directly from peripheral blood of patients
      receiving rIL-2. CD56- cells from patients but not normal individuals developed
      significant LAK cytolytic activity against NK-resistant COLO 205 targets (16 +/-
      3 LU/10(6) cells) when cultured for 3 days with 1500 units/ml rIL-2. The CD56-
      LAK precursor activity was confined to cells expressing a CD56-CD16+ phenotype
      and a large granular lymphocyte morphology; little or no NK or LAK precursor
      activity was detectable in CD56-CD5+ T-cells from patients. Phenotypic
      characterization of CD16+CD56- cells revealed that this population is uniformly
      CD11a+,CD18+, and CD38+ and is heterogeneous in its expression of CD11b, CD11c,
      and CD16/Leu 11c. These results indicate that rIL-2 administration induces
      enhanced LAK precursor activity in a novel population of CD5-CD16+CD56- cells.

PMID- 1384960
TI  - Effects of differentiating agents on cell surface expression of the breast
      carcinoma-associated DF3-P epitope.
AB  - The DF3 antigen is a member of a family of high-molecular-weight glycoproteins
      aberrantly expressed in human breast carcinomas. Recent work has described the
      generation of a monoclonal antibody (MAb), designated DF3-P, that reacts with
      immature, underglycosylated precursors of DF3 antigen. Immunoperoxidase staining
      studies have demonstrated that MAb DF3-P exhibits selective reactivity with
      malignant mammary epithelium. Using flow cytometry and live cell
      radioimmunoassays, the present studies demonstrate that the epitope recognized by
      MAb DF3-P is expressed on the surface of MCF-7 and other human breast carcinoma
      cell lines. We also demonstrate that treatment of MCF-7 cells with 12-O
      tetradecanoylphorbol-13-acetate, an agent known to induce a more differentiated
      mammary cell phenotype, is associated with increased expression of the DF3-P
      epitope. Similar findings were obtained with sodium butyrate. The results
      indicate that these agents increase both cell surface DF3-P antigen density and
      the percentage of DF3-P-positive cells. Immunofluorescence studies performed on
      chamber slides further demonstrate that MAb DF3-P-reactive cells are detectable
      in small clones or clusters. Similar studies with 12-O-tetradecanoylphorbol-13
      acetate- and butyrate-treated cells demonstrate increases in the size and number
      of these clusters. Taken together, these results indicate that the DF3-P epitope
      is expressed on the surface of human breast carcinoma cell lines and that the
      heterogeneity of this expression is related to the presence of differentiating
      signals.

PMID- 1384961
TI  - Intracellular localization of human DNA repair enzyme methylguanine-DNA
      methyltransferase by antibodies and its importance.
AB  - The human DNA repair enzyme, methylguanine-DNA methyltransferase (MGMT, M(r)
      21,000), which protects cells against the mutagenic effect of alkylating
      carcinogens, was found to be localized in the cell nucleus (except the nucleolus)
      by immunofluorescence staining using polyclonal and monoclonal antibodies. The
      supporting experiments came from differential staining of the MGMT-deficient (mer
      ) and -proficient (mer+) cells, Western blotting analysis, and specific antibody
      depletion studies with the immobilized fusion protein, GSTMGMT-glutathione
      Sepharose. Its localization in the nucleus agrees with its biological function
      and possibly explains the ineffective protection of mammalian cells (mer-)
      transfected with the Escherichia coli MGMT genes from bifunctional alkylating
      agents.

PMID- 1384962
TI  - Monoclonal antibodies to the myogenic regulatory protein MyoD1: epitope mapping
      and diagnostic utility.
AB  - Monoclonal antibodies (MoAbs) were developed against recombinant wild-type murine
      MyoD1 protein. Each of 4 MoAbs was immunologically reactive with recombinant
      MyoD1 protein by enzyme-linked immunosorbent assay, and each specifically stained
      the nuclei of myogenic cells. Epitopes were mapped using fusion protein
      constructs with specific deletions of defined regions of the MyoD1 molecule. MoAb
      5.2F recognized an epitope in the amino terminal region between amino acid
      residues (AAR) 3 and 56, whereas epitopes for MoAbs 1.1A, 5.4G, and 5.8A were in
      the carboxyl terminus (AAR 167-318) of the MyoD1 protein. The epitope for MoAb
      5.8A was further delineated to AAR 170-209 by Western analysis and
      immunoprecipitation of in vivo transcribed and translated MyoD1 protein having
      specific deletions in the carboxyl terminus. The 5.8A epitope was ultimately
      localized to the region between AAR 180 and 189 of the protein by enzyme-linked
      immunosorbent assay using 10-amino acid residue synthetic peptides. This sequence
      is apparently unique to MyoD1 and has little homology to other myogenic
      regulatory proteins (myogenin, Myf5, Myf6, and MRF4). Transfection of cDNA for
      murine MyoD1 into a nonmuscle cell line conferred 5.8A reactivity, confirming the
      specificity of this reagent. MoAb 5.8A was then used to examine the expression of
      MyoD1 in normal and malignant human tissues. MyoD1 was not detected in any normal
      adult tissue but was detected in 25 of 25 histologically confirmed
      rhabdomyosarcomas. Staining was localized to the nucleus and showed marked
      heterogeneity between cells as well as differential staining within nuclei.
      Specific subcellular localization of 5.8A was further determined by
      immunoelectron microscopy, where antibody was found to localize to electron-dense
      areas, more frequently associated with the nuclear submembranous region. In
      addition to rhabdomyosarcomas, MoAb 5.8A stained 2 of 5 Wilms' tumors and one
      ectomesenchymoma, neoplasms known to contain myogenic elements. The 5.8A reagent
      was also of value in the accurate histopathological classification of 2 of 4
      tumors previously diagnosed as extraosseous Ewing's sarcoma and 2 of 3 tumors
      diagnosed as undifferentiated sarcomas.

PMID- 1384963
TI  - Antitumor effect of interferon plus cyclosporine A following chemotherapy for
      disseminated melanoma.
AB  - Interferon (IFN) increases the expression of major histocompatibility (MHC)
      antigens on the surface of tumor cells. Cyclosporine A (CsA) administration
      following myeloablative therapy and syngeneic bone marrow transplantation results
      in the generation of cells with autoreactive and antitumor effects that are
      related to the expression of MHC antigens. We used these two agents following
      conventional chemotherapy in a non-bone marrow transplantation setting for a
      melanoma in a murine model. Treatment with IFN alone or CsA alone was ineffective
      in controlling the dissemination of melanoma. A combination therapy with both
      these agents resulted in a significant control in the dissemination of the tumor,
      prolonged the survival of the tumor-bearing mice over that with chemotherapy
      alone, and generated cells with potent MHC-unrestricted cytotoxic potential in
      vitro. Adoptive transfer of these cells to secondary tumor bearers treated with
      chemotherapy showed potent antitumor effect; in the absence of chemotherapy,
      these cells had no antitumor effect in the secondary recipients. The antitumor
      effect of cells generated by IFN plus CsA therapy following chemotherapy could be
      blocked by normal spleen cells. These data suggest that treatment with IFN plus
      CsA following nonmyeloablative chemotherapy generates cells with MHC-unrestricted
      cytotoxicity; this effect may be related to abolition of suppressor influences by
      the chemotherapy.

PMID- 1384964
TI  - A retrovirus in chinook salmon (Oncorhynchus tshawytscha) with plasmacytoid
      leukemia and evidence for the etiology of the disease.
AB  - A plasmacytoid leukemia (PL) has caused mortalities in chinook salmon
      (Oncorhynchus tshawytscha) reared in seawater netpens in western British
      Columbia, Canada, since 1988. Kidney or eye tissues from 11 of 13 fish from
      netpens with clinical PL had reverse transcriptase (RT) activity. This RT
      activity was associated with virus particles of retrovirus morphology and buoyant
      density. In a transmission experiment, PL-positive donor fish tissues also had RT
      activity and virus particles of retrovirus morphology and buoyant density, as did
      recipient fish tissues following development of the disease 6 weeks postinjection
      with a tissue homogenate from the donor fish. Kidney and spleen tissues from fish
      that developed PL following injection with an inoculum that was passed through a
      0.22-micron filter, in a separate experiment (M. L. Kent and S. C. Dawe. Further
      evidence for a viral etiology in the plasmacytoid leukemia of chinook salmon
      Oncorhynchus tshawytscha. Dis. Aquat. Org., in press, 1992), also exhibited RT
      activity. The virus particles observed by electron-microscopic examination of
      tissues or sucrose fractions from PL-positive fish were enveloped and were about
      110-nm diameter with a central electron-dense core. Polypeptides of about M(r)
      120,000, 80,000, 42,000, 27,000, 25,000, 22,000, and 19,000 were observed when
      purified virus particles were examined by polyacrylamide gel electrophoresis
      analysis. Many infectious neoplasms of animals, including fishes, are caused by
      retroviruses. The evidence in this study shows the presence of a retrovirus in
      chinook salmon with PL and further suggests a retroviral etiology of the disease.
      We are tentatively calling this virus salmon leukemia virus.

PMID- 1384965
TI  - Angiogenesis, microvascular architecture, microhemodynamics, and interstitial
      fluid pressure during early growth of human adenocarcinoma LS174T in SCID mice.
AB  - To date, most quantitative information on tumor angiogenesis, microcirculation,
      and transport has been derived from rodent tumors grown in transparent chamber
      preparations. In this paper we present a chamber technique adapted to
      immunodeficient mice for the study of human tumor xenografts. Microcirculatory
      parameters in severe combined immunodeficient mice bearing a dorsal skin fold
      chamber preparation were quantified using intravital microscopy and image
      analysis. The take rate of the human colon adenocarcinoma LS174T in the chamber
      preparation was 100%, and the tumor area doubling time was 6.5 days. Three days
      following implantation of 2 x 10(5) tumor cells onto the striated skin muscle,
      capillary sprouts were noted in the tumor cell mass. Microvasculature in the
      tumors was established after 10 days. Capillary density, vessel diameter, red
      blood cell velocity, and blood flow rates in individual microvessels measured on
      days 10, 14, 18, and 22 showed no statistical difference in the striated muscle
      (capillaries) and subcutaneous tissue (arterioles and venules) of the skin of
      tumor-free animals (N = 6), whereas these parameters increased slightly, but not
      significantly, in the LS174T tumors (N = 7). Mean interstitial fluid pressure (+/
      SD) in these small tumors was 4.6 +/- 1.7 mmHg (N = 4) on day 10 and 5.1 +/- 0.9
      mmHg (N = 4) on day 22 and significantly elevated compared to that in the
      subcutaneous and skin tissue (-0.9 +/- 0.8 mmHg) (N = 4) (P < 0.001). To our
      knowledge, this is the first model enabling intravital microscopic studies of
      human tumor xenografts in a transparent chamber preparation in severe combined
      immunodeficient mice. Studies on angiogenesis, microcirculation, and transport
      using such a preparation should provide new insights into microcirculation
      mediated mechanisms for cancer treatment.

PMID- 1384966
TI  - Ex vivo differentiation therapy as a method of leukemic cell purging in murine
      bone marrow expansion cultures.
AB  - We investigated the use of differentiation therapy as a method of purging bone
      marrow (BM) of leukemic cells in ex vivo murine BM expansion cultures (delta
      cultures). In clonal cultures and in suspension cultures a combination of the
      differentiation-inducing agents granulocyte colony-stimulating factor (G-CSF),
      interleukin (IL)-6, and all-trans-retinoic acid (ATRA) was found to be most
      effective in inducing the differentiation of the murine myelomonocytic leukemic
      cell line WEHI 3B D+ LacZ clone 2.8 (clone 2.8). Furthermore, we investigated the
      activity of a mutant form of IL-6, mutein, and found it to have a greater
      specific activity in cell proliferation assays and in a clone 2.8 differentiation
      assay than the native form of IL-6. Coculture of clone 2.8 and BM in IL-1 and kit
      ligand-stimulated delta-cultures showed that the added stimuli, G-CSF, mutein,
      and ATRA, decreased the expansion of leukemic cells. Mice transplanted with G
      CSF, mutein, and ATRA-purged BM had an increased survival time relative to
      nonpurged controls. The addition of G-CSF, mutein, and ATRA to delta-cultures did
      not result in any impairment of hematopoietic stem cells when measured 5 wk after
      transplantation.

PMID- 1384967
TI  - Loss of keratin expression in anaplastic carcinoma cells due to
      posttranscriptional down-regulation acting in trans.
AB  - Rat keratin K5 and vimentin complementary DNAs have been isolated, identified,
      and used to study keratin and vimentin expression as markers for cell
      differentiation. Isologous rat neoplastic epithelial cell lines used were based
      on a clonal benign epithelial line (A5P/B10) and a clonal anaplastic malignant
      derivative line (T952/F7). Stable cytoplasmic mRNA was detected for keratin but
      not vimentin in the benign cells. The anaplastic derivative cells expressed
      vimentin but showed a 1000-fold reduction in the keratin message, which nuclear
      run-on assays identified as being due to posttranscriptional down-regulation. An
      identical pattern of posttranscriptional down-regulation was found in independent
      malignant somatic cell hybrids of the benign and anaplastic cells. trans-acting
      regulatory mechanisms implicated in posttranscriptional (pretranslational)
      keratin down-regulation in these anaplastic malignant cells may play a role in
      the apparent loss of differentiation evident in tumor progression.

PMID- 1384969
TI  - Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and
      metastatic disease.
AB  - The formation of a blood supply (angiogenesis) is critical to the growth of solid
      tumors. The naturally occurring steroid tetrahydrocortisol, the synthetic
      cyclodextrin derivative beta-cyclodextrin tetradecasulfate, and the tetracycline
      derivative minocycline have antiangiogenic activity. Tetrahydrocortisol and beta
      cyclodextrin tetradecasulfate in a 1:1 molar ratio by continuous infusion over 14
      days and minocycline administered i.p. over 14 days from day 4 to day 18
      postimplantation of the Lewis lung carcinoma significantly increased the growth
      delay of the primary tumor after treatment with cis-diamminedichloroplatinum(II),
      melphalan, cyclophosphamide, Adriamycin, bleomycin, and radiation therapy
      administered in standard regimens. Addition of the antiangiogenic agents to
      treatment with the cytotoxic therapies not only reduced the number of lung
      metastases formed from the primary tumor but also reduced the number of large
      metastases. Five of 12 animals treated with the antiangiogenic modulators and
      cyclophosphamide were long-term survivors (> 120 days). Thus, antiangiogenic
      therapies can potentiate the efficacy of standard anticancer therapies.

PMID- 1384968
TI  - Human glucocorticoid receptor gene deletion following exposure to cancer
      chemotherapeutic drugs and chemical mutagens.
AB  - The sensitivity of the human glucocorticoid receptor (hGR) gene to mutagenesis by
      the cancer chemotherapeutic drugs adriamycin, bleomycin, and chlorambucil was
      evaluated using glucocorticoid-sensitive (dexs) subclones of the human leukemic
      cell line CEM-C7. Treatment of cells with either bleomycin or chlorambucil
      increased the frequency of glucocorticoid-resistant (dexr) clones 3.3- and 10
      fold, respectively. Measurement of steroid-binding activity in intact dexr cells
      demonstrated that the predominant phenotype of drug-induced dexr clones was
      receptorless (r-). dexs CEM cells express only one functional hGR allele and, in
      addition, are heterozygous for a BclI restriction fragment length polymorphism in
      the hGR gene (L. A. Palmer and J. M. Harmon, Cancer Res., 51:5224-5231, 1991). To
      determine the basis of the r- phenotype, BclI digests of genomic DNA isolated
      from r+ and r- cell lines were examined for the presence of the polymorphic 2.4-
      and 4.4-kilobase digestion products. A deletion of all or part of the hGR gene
      was demonstrated by the absence of the 4.4-kilobase fragment in one of two
      bleomycin-induced dexr clones, as well as the ICR191-induced dexr cell line
      ICR27TK.3. Cytogenetic analysis of ICR27TK.3 showed that the distal portion of
      the long arm of one chromosome 5 had been replaced with a portion of chromosome
      15. Thus, in at least two dexr cell lines, deletions and/or chromosome breaks in
      the hGR locus appear to account for the r- phenotype.

PMID- 1384970
TI  - Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP
      induced parkinsonian monkeys.
AB  - The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent,
      on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys
      (Macaca fascicularis) were treated with three injections of MPTP hydrochloride
      (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of
      the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms
      manifested for greater than 1 year were used. The animals developed mild to
      moderate degrees of postural or kinetic tremor, and their motor activity was
      reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor
      in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in
      suppressing the tremor. However, the application of propranolol induced emesis,
      whereas arotinolol had no adverse effects. These results suggest that arotinolol
      is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

PMID- 1384971
TI  - Structure of the polysaccharide O-antigen of Salmonella riogrande O:40 (group R)
      related to blood group A activity.
AB  - The structure of the Salmonella O:40 (Group R) antigen was determined from an
      analysis of the antigenic O-polysaccharide component of the lipopolysaccharide
      produced by Salmonella riogrande O:40. Using 1H- and 13C-NMR spectroscopy,
      methylation analysis, and periodate degradation methods, the O-polysaccharide was
      found to be a high molecular weight branched polymer of repeating pentasaccharide
      units having the structure: [formula: see text] The reported human blood group A
      activity was concluded to reside in an epitope of a terminal trisaccharide
      portion of the O-chain involving alpha-D-GalpNAc and beta-D-GlcpNAc residues
      linked (1----3) and (1----2), respectively, to beta-D-Manp branched residues in
      which the alpha-D-GalpNAc residue would appear to be the critical antigenic
      factor recognized by polyclonal blood group A antisera.

PMID- 1384972
TI  - Comparison of cyclic GMP in human internal mammary artery and saphenous vein:
      implications for coronary artery bypass graft patency.
AB  - OBJECTIVE: The aim was to examine the capacity of the human saphenous vein
      (native and surgically prepared) and the internal mammary artery to generate
      cyclic GMP, the second messenger that mediates smooth muscle relaxation following
      production of nitric oxide. METHODS: 209 vessel segments were used from 22
      patients undergoing coronary revascularisation. Isolated vessel segments were
      stimulated with a range of endothelium dependent and endothelium independent
      agonists and flash frozen for radioimmunoassay for cyclic GMP. RESULTS:
      Control/basal levels of cyclic GMP were significantly higher in the internal
      mammary artery than either native or distended saphenous vein. Endothelium
      dependent agonist stimulation with acetylcholine, bradykinin, or substance P
      induced significant increases in cyclic GMP in internal mammary artery and native
      saphenous vein, whereas distended veins showed non-significant changes in
      response to agonist stimulation. Endothelium removal abolished agonist stimulated
      increases in cyclic GMP. Glyceryl trinitrate and sodium nitroprusside elicited
      significant further increases in cyclic GMP in native vein and internal mammary
      artery. All values obtained were significantly greater in arterial than in venous
      tissue. CONCLUSION: Differences in basal and stimulated cyclic GMP activity in
      arteries and veins have been shown. This could represent an additional protective
      mechanism against constrictor influences in arterial bypass grafts, which may
      explain their documented better long term performance.

PMID- 1384973
TI  - The premature beat.

PMID- 1384974
TI  - Ontogeny of substance P-, CGRP-, and VIP-containing nerve fibers in the amphibian
      carotid labyrinth of the bullfrog, Rana catesbeiana. An immunohistochemical
      study.
AB  - The ontogeny of substance P, CGRP (calcitonin gene-related peptide), and VIP
      (vasoactive intestinal polypeptide) containing nerve fibers in the carotid
      labyrinth of the bullfrog, Rana catesbeiana, was examined by the peroxidase
      antiperoxidase method. The time of appearance of these three peptides was
      different for each. First, CGRP fibers appeared in the wall of the carotid arch
      and external carotid arteries, and in a thin septum between these two arteries at
      an early stage of larval development (stage III). At stage V, substance P
      immunoreactive fibers appeared, and VIP fibers were detected at the early
      metamorphic stage (stage XXII). Up to the completion of metamorphosis, the number
      of these fibers remained low. From 1 to 5 weeks after metamorphosis, substance P,
      CGRP, and VIP fibers increased in number to varying degrees. By 8 weeks after
      metamorphosis, the distribution and abundance of these fibers closely resembled
      those of the adults. Some CGRP and VIP immunoreactive glomus cells were found at
      the stages immediately before and after the completion of metamorphosis. These
      findings suggest that substance P, CGRP, and VIP fibers during larval development
      and metamorphosis may be nonfunctional, and start to participate in vascular
      regulation only after metamorphosis. The transient CGRP and VIP in some glomus
      cells may be important for the development of the labyrinth, or may take part in
      vascular regulation through the close apposition of the glomus and smooth muscle
      cells (g-s connection).

PMID- 1384975
TI  - Projections and pathways of submucous neurons to the mucosa of the guinea-pig
      small intestine.
AB  - Double-labelling immunohistochemistry and retrograde transport of the
      carbocyanine dye, DiI, were used to establish the pathways of submucous neurons
      to the mucosa of the guinea-pig small intestine. Following the application of DiI
      to a villus, DiI-labelled nerve cell bodies were found in the submucous plexus up
      to 8.3 mm circumferentially and 3.8 mm longitudinally. The size of each of the
      four characterised classes of submucous neurons was determined and their
      distributions and projections mapped. Cells characterised by vasoactive
      intestinal polypeptide immunoreactivity accounted for 52% of DiI-labelled cells
      and had the longest projections. Cells characterised by neuropeptide Y (19%) or
      by calretinin immunoreactivity (13% of all DiI-labelled neurons) had relatively
      short projections and cells with substance P immunoreactivity (20%) had
      intermediate lengths of projection. When DiI was applied directly to the
      submucous plexus, filled neurons of all classes had significantly shorter
      projections, indicating that they must run for considerable distances in other
      pathways to the mucosa, probably via the non-ganglionated plexus. On average,
      each villus is innervated by at least 70 submucous neurons. From quantitative
      estimates there are 9 submucous neurons per villus. Thus, each submucous neuron
      is likely to supply about 8 villi. This demonstrates a high degree of convergence
      and divergence in the innervation of the mucosa.

PMID- 1384976
TI  - Splenic primary sensory afferents in the guinea pig demonstrated with
      anterogradely transported wheat-germ agglutinin conjugated to horseradish
      peroxidase.
AB  - The distribution of primary visceral afferents to the spleen of the guinea pig
      was studied after injections of wheat-germ agglutinin conjugated to horseradish
      peroxidase (HRP) into the left dorsal root ganglia at levels T7-T12. After
      anterograde transport of the tracer, labeled fibers were found in the nerves
      around the splenic artery in the hilus region and in the splenic parenchyma. The
      majority of labeled fibers in the spleen were detected in the white pulp. HRP
      positive fibers were also observed in the red pulp and in the trabeculae. The
      distribution of the HRP-labeled fibers was in part similar to those of substance
      P-immunoreactive and calcitonin gene-related peptide-immunoreactive nerve
      structures. The results show that the anterograde tracing technique can be used
      successfully to investigate splenic primary afferent innervation.

PMID- 1384977
TI  - Comparative study of the olfactory epithelium of the three-spined stickleback
      (Gasterosteus aculeatus) and the nine-spined stickleback (Pungitius pungitius).
AB  - The olfactory epithelium of the three-spined stickleback (Gasterosteus aculeatus)
      and the nine-spined stickleback (Pungitius pungitius) has been studied with a
      conventional histochemical and a novel immunological staining technique. In both
      species, the sensory epithelium is arranged in folds separated by non-sensory
      epithelial tissue. In the nine-spined stickleback, intrinsic folds consisting of
      non-sensory cells are found in the apical part of the sensory epithelium where
      they divide the surface of the sensory epithelium into small islets. These non
      sensory cells are non-ciliated, flattened and piled on top of each other; they
      contain numerous electron-translucent vesicles. The intrinsic folds are absent
      from the sensory epithelium of the three-spined stickleback. In both species,
      axons of receptor cells form a layer of fibers in the sensory epithelium
      immediately above the basal cells. In the three-spined stickleback, thick
      branches of the olfactory nerve are frequently found in this layer. These
      branches are only occasionally observed in the sensory epithelium of the nine
      spined stickleback. Thus, the three-spined stickleback and the nine-spined
      stickleback show considerable differences in the organization of the sensory
      regions of the olfactory epithelium.

PMID- 1384978
TI  - Co-localization of vimentin and cytokeratins in M-cells of rabbit gut-associated
      lymphoid tissue (GALT).
AB  - The occurrence of cytokeratins, vimentin, and desmin in the dome epithelia and
      adjacent non-dome epithelia in four locations of gut-associated lymphoid tissues
      (GALT) of adult and newborn rabbits (Peyer's patches, sacculus rotundus, caecal
      lymphoid patches and appendix) was studied with monoclonal antibodies, using the
      indirect immunoperoxidase technique. In all locations investigated in adult
      animals, antibodies specific for vimentin labelled (1) M-cells, which engulf
      intra-epithelial lymphocytes, (2) columnar epithelial cells at the base of the
      domes lacking an apparent contact with lymphocytes ("immature" M-cells), and (3)
      flat cells, which lie in the lamina propria under the dome epithelium, and which
      line the basal lamina with thin cytoplasmic processes. In newborn rabbits,
      columnar epithelial cells resembling the immature M-cells of adults were
      selectively stained with vimentin antibodies. In M-cells, the strongest
      immunoreactivity was present in the perinuclear region and close to the pocket
      membrane, whereas the most apical and most basal parts of the cytoplasm showed no
      vimentin-immunoreactivity. Enterocytes in the dome epithelium and in the non-dome
      epithelium were vimentin-negative. M-cells and enterocytes bound antibodies
      against cytokeratin peptides 18 and 19 in adult and newborn animals. Compared
      with enterocytes, M-cells showed less intense staining for cytokeratins. Dome
      epithelia and no-dome epithelia did not contain desmin-immunoreactive cells. The
      results suggest that vimentin is a sensitive marker for M-cells in rabbit GALT.

PMID- 1384979
TI  - Nucleolar morphology and rDNA in situ hybridisation in monocytes.
AB  - The aim of this study was to correlate morphological changes of nucleoli of non
      proliferating monocytes to their functional activity, since nucleolar morphology
      is currently considered as a diagnostic marker for cell proliferation. Monocytes
      from healthy donors were fractionated by current counterflow centrifugation and
      kept in culture for 6 days. Cells were stimulated by the addition of 200 units/ml
      interferon gamma (IFN gamma). Under this stimulus the monocytes show no
      proliferation but a strongly augmented expression of type I Fc IgG receptor,
      human leucocyte antigen DR, human leucocyte antigen DP and human leucocyte
      antigen DQ. Morphological changes after stimulation included the appearance of
      multinucleated cells, typical signs of the activation of rRNA synthesis indicated
      by an increase in nucleolar size, and changes in nucleolar structure such as the
      appearance of reticulate and compact nucleoli. The number of nucleolus organiser
      regions (NORs) visualised by in situ hybridisation was compared with the position
      and number of nucleoli visualised by silver staining in interphase cells. In
      comparison with control cultures, activated monocytes show a distinct increase in
      the number of those NORs that take part in the formation of nucleoli. Our results
      show that, in non-proliferating activated monocytes, the morphology of nucleoli
      and the increase of NOR activity are similar to those in proliferating cells. NOR
      activation is therefore an indicator for cellular activity, but is not
      necessarily correlated with proliferation.

PMID- 1384980
TI  - The distribution and colocalization of neuropeptides in perivascular nerves
      innervating the large arteries and veins of the snake, Elaphe obsoleta.
AB  - Single- and dual-labelling immunohistochemistry were used to determine the
      distribution and coexistence of neuropeptides in perivascular nerves of the large
      arteries and veins of the snake, Elaphe obsoleta, using antibodies for vasoactive
      intestinal polypeptide, substance P, calcitonin gene-related peptide,
      neuropeptide Y, galanin, somatostatin, and leu-enkephalin. Blood vessels were
      sampled from four regions along the body of the snake: region 1, arteries and
      veins anterior to the heart; region 2, central vasculature 5 cm anterior and 10
      cm posterior to the heart; region 3, arteries and veins in a 30-cm region
      posterior to the liver; and region 4, dorsal aorta and renal arteries, renal and
      intestinal veins, 5-30 cm cephalad of the vent. A moderate to dense distribution
      of vasoactive intestinal polypeptide-like immunoreactive fibres was found in most
      arteries and veins of regions 1-3, but fibres were absent from the vessels of
      region 4. The majority of vasoactive intestinal polypeptide-like immunoreactive
      fibres contained colocalized substance P-like immunoreactivity, and these fibres
      were unaffected by either capsaicin or 6-hydroxydopamine (6-OHDA) pretreatment.
      In the anterior section of the snake, the vagal trunks contained many cell bodies
      with colocalized vasoactive intestinal polypeptide and substance P-like
      immunoreactivity. It is suggested that the vasoactive intestinal
      polypeptide/substance P-like immunoreactive cell bodies and fibres are
      parasympathetic postganglionic nerves. Neuropeptide Y-like immunoreactive fibres
      were observed in all arteries and veins, being most dense in regions 3 and 4. The
      majority of these fibres also contained colocalized galanin-like
      immunoreactivity, and were absent in tissues from 6-OHDA pretreated snakes,
      suggesting that neuropeptide Y and galanin are colocalized in adrenergic nerves.
      A small number of neuropeptide Y-like immunoreactive fibres contained vasoactive
      intestinal polypeptide but not galanin, and were unaffected by 6-OHDA treatment.
      All calcitonin gene-related peptide-like immunoreactive fibres contained
      colocalized substance P-like immunoreactivity, and these fibres were observed in
      all vessels, being particularly dense in the carotid artery and jugular veins.
      All calcitonin gene-related peptide/substance P-like immunoreactive fibres
      appeared damaged after capsaicin treatment suggesting they represent fibres from
      afferent sensory neurons. A sparse plexus of somatostatin-like immunoreactive
      fibres was observed in the vessels only from region 4. No enkephalin-like
      immunoreactive fibres were found in any blood vessels from any region. This study
      provides morphological evidence to suggest that there is considerable functional
      specialization within the components of the rat snake peripheral autonomic system
      controlling the circulation, in particular the regulation of venous capacitance.

PMID- 1384982
TI  - Axoplasmic transport of horseradish peroxidase in single neurons of the dorsal
      root ganglion studied in vitro by microinjection.
AB  - The dependence of anterograde axoplasmic transport on cytoskeletal components was
      investigated using microinjection of horseradish peroxidase (HRP) into the somata
      of chick dorsal root ganglion cells in vitro. Microinjected HRP was transported
      anterogradely in the neurites and their branches; this transport was disturbed by
      colchicine in a drug-dependent and time-dependent manner. Cytochalasin B, a drug
      that depolymerizes actin, did not inhibit the transport of HRP, despite the
      formation of local swellings in neurites. The microinjection of polyclonal
      antibodies directed against tubulin and monoclonal antibodies (mAbs) against 200
      kDa neurofilaments disturbed the axoplasmic transport of co-injected HRP, which
      then exhibited an irregular and discontinuous distribution in the axonal
      branches. The transport of HRP became discontinuous after the injection of anti
      tubulin antibodies and led to the formation of globular deposits of HRP.
      Polyclonal antibodies against actin and mAbs to 160-kDa and 68-kDa neurofilaments
      seemed to have no effect on the axoplasmic transport of co-injected HRP.
      Microinjection of antibodies against tubulin induced formation of perinuclear
      bundles consisting of cytoskeletal components. The transport of HRP thus appears
      to be regulated by an intact microtubular system and cross-linker components (200
      kDa neurofilaments) of the cytoskeleton. Actin and most intermediate filament
      proteins do not seem to play an essential role in the transport of HRP.

PMID- 1384981
TI  - Light- and electron-microscopic immunochemical analysis of nerve fibre types
      innervating the taenia of the guinea-pig caecum.
AB  - The present work was undertaken to determine by immunocytochemical methods which
      of the putative enteric neurotransmitters are contained in axons supplying the
      guinea-pig taenia coli and what proportion of axons is accounted for by the
      presence of these substances. Numerous fibres displayed immunoreactivity for
      dynorphin (DYN), enkephalin (ENK), gamma-aminobutyric acid (GABA), nitric oxide
      synthase (NOS), substance P (SP) and vasoactive intestinal peptide (VIP), but, in
      contrast to other gut regions, fibres showing immunoreactivity for gastrin
      releasing peptide, galanin and neuropeptide Y were rare in the taenia. Fibres
      reactive for calbindin, calcitonin gene-related peptide, cholecystokinin, 5
      hydroxytryptamine and somatostatin were also rare. Tyrosine hydroxylase-like
      immunoreactivity (TH-LI) was present in numerous fibres that disappeared after
      extrinsic denervation, a procedure that did not detectably affect any of the
      other major groups of fibres. Simultaneous staining of extrinsically denervated
      preparations revealed that SP-LI and VIP-LI were located in separate fibres, and
      ultrastructural studies showed these to be 58% and 33% of intrinsic fibres
      supplying the muscle. Immunoreactivity for the general marker, neuron-specific
      enolase, was located in 95-98% of axons. ENK-LI and DYN-LI were in the same
      axons, and similar proportions of the fibres with either SP-LI or VIP-LI, about
      85%, contained immunoreactivity for ENK and DYN. All VIP-LI fibres, but no SP-LI
      fibres, were reactive for NOS. The results imply that the taenia of the guinea
      pig caecum is innervated by two major groups of enteric neurons: (i) excitatory
      neurons that contain ACh, SP, other tachykinins, and, in most cases, DYN-LI and
      ENK-LI; and (ii) inhibitory neurons that contain NOS-LI, VIP-LI, in most cases,
      the two opioids and, quite probably, ATP as a transmitter. GABA-LI is contained
      in a smaller population of intrinsic axons. Even though the taenia represents one
      of the simplest tissues for examining transmission from enteric neurons to
      intestinal muscle, it shares some of the complexity of other regions, in that
      four major axon types supply the muscle and both the enteric excitatory and
      enteric inhibitory neurons contain multiple transmitters.

PMID- 1384983
TI  - Enterochromaffin-like cells in the rat stomach: effect of alpha
      fluoromethylhistidine-evoked histamine depletion. A chemical, histochemical and
      electron-microscopic study.
AB  - In the rat, gastric histamine is stored predominantly in the enterochromaffin
      like (ECL) cells, which are located basally in the oxyntic mucosa. The functional
      significance of histamine in the ECL cells is a matter of speculation. In this
      study the effect of depletion of histamine on the properties and ultrastructure
      of the ECL cells was examined. Histamine synthesis was inhibited with alpha
      fluoromethylhistidine (3 mg.kg-1.h-1) given via osmotic minipumps over a period
      of 24 h. The treatment reduced the histidine decarboxylase activity
      (approximately 20% remaining) and histamine concentration (less than 20%
      remaining) in the oxyntic mucosa, as well as the intensity of histamine- and
      chromogranin A-immunostaining in the ECL cells, compared to control rats. The
      cytoplasmic (secretory) granules/vesicles were greatly reduced in number and size
      following alpha-fluoromethylhistidine administration. The histamine
      immunostaining of the mast cells, which occurs at the mucosal surface and in the
      submucosa, appeared unaffected. We conclude that ECL cell histamine accounts for
      at least 80% of the total oxyntic mucosal histamine in the rat and that it
      represents a more mobile pool than mast cell histamine. The reduction in the
      number and size of the ECL cell granules/vesicles following histamine depletion
      is in accord with the idea that they represent the storage site for histamine.

PMID- 1384984
TI  - Actions of two native GnRHs and protein kinase C modulators on goldfish pituitary
      cells. Studies on intracellular calcium levels and gonadotropin release.
AB  - Previous results indicate that the two native gonadotropin (GtH)-releasing
      hormones of the goldfish, sGnRH and cGnRHII, stimulate GtH secretion in an
      extracellular Ca2+ ([Ca2+]o) dependent manner. In the present study, sGnRH,
      cGnRHII, KCI and the protein kinase C (PKC) activators TPA and DiC8, stimulated
      increases in intracellular Ca2+ ([Ca2+]i) levels in goldfish pituitary cells.
      Testing in Ca(2+)-deficient medium abolished the [Ca2+]i responses to cGnRHII,
      TPA and KCI and attenuated responses to sGnRH and DiC8. These results are the
      first to demonstrate that in teleost pituitary cells both native GnRHs stimulate
      increases in [Ca2+]i levels via [Ca2+]o entry. sGnRH- and DiC8-stimulated
      increases in [Ca2+]i also appear to be partially due to mobilization of Ca2+ from
      intracellular stores. Other results are consistent with a role for PKC in
      mediating GnRH action especially extracellular Ca2+ entry. Firstly, the PKC
      inhibitor staurosporine decreased GnRH- and TPA-induced [Ca2+]i responses.
      Secondly, incubation with Ca(2+)-deficient medium attenuated TPA- and DiC8
      stimulated GtH release. Thirdly, GtH release responses to PKC activators were
      enhanced and reduced by an agonist and an antagonist of Ca2+ channel function,
      respectively. However, differences in the sensitivity of DiC8- and TPA-elicited
      responses to manipulations of [Ca2+]o entry indicate that these two PKC
      activators may have different actions in the goldfish pituitary. A difference in
      action of the two GnRHs on mobilization of Ca2+ from intracellular stores is also
      indicated.

PMID- 1384985
TI  - Prevalence of adult migraine in general practice.
AB  - In 1988 the International Headache Society presented new criteria for the
      diagnosis of migraine. We used these criteria in a questionnaire to assist in the
      diagnosis of migraine. The questionnaire was answered by 230 patients in four
      general practices. We found a migraine prevalence of 11.7%. More than 70% of
      migraine patients had 12 or more attacks per year, and the length of attack
      varied between 4 and 24 h in 80% of them. The majority of migraineurs went to bed
      during the attack and 55% had stayed away from work due to migraine during the
      last year. The results of this study are in agreement with others. Migraine is an
      appreciable economic concern due to frequent short absenteeism from work.

PMID- 1384986
TI  - Interpretation of cardiac pathophysiology from pressure waveform analysis:
      cardiac arrhythmias.
AB  - Various arrhythmias can produce distorted pressure waveforms, which may be
      confused with benign physiologic events. Delay in the management of serious
      arrhythmias can be avoided by vigilant monitoring of systemic pressures.

PMID- 1384987
TI  - UNC-5, a transmembrane protein with immunoglobulin and thrombospondin type 1
      domains, guides cell and pioneer axon migrations in C. elegans.
AB  - The unc-5 gene is required for guiding pioneering axons and migrating cells along
      the body wall in C. elegans. In mutants, dorsal migrations are disrupted, but
      ventral and longitudinal movements are largely unaffected. The gene was tagged
      for molecular cloning by transposon insertions. Based on genomic and cDNA
      sequencing, the gene encodes UNC-5, a transmembrane protein of 919 aa. The
      predicted extracellular N-terminus comprises two immunoglobulin and two
      thrombospondin type 1 domains. Except for an SH3-like motif, the large
      intracellular C-terminus is novel. Mosaic analysis shows that unc-5 acts in
      migrating cells and pioneering neurons. We propose that UNC-5 is a transmembrane
      receptor expressed on the surface of motile cells and growth cones to guide
      dorsal movements.

PMID- 1384988
TI  - Mouse P0 gene disruption leads to hypomyelination, abnormal expression of
      recognition molecules, and degeneration of myelin and axons.
AB  - We have used homologous recombination in embryonic stem cells to generate mice
      carrying a mutation in the gene encoding P0, an immunoglobulin-related
      recognition molecule and the major protein of peripheral nervous system myelin.
      These mice are deficient in normal motor coordination and exhibit tremors and
      occasional convulsions. Axons in their peripheral nerves are severely
      hypomyelinated and a subset of myelin-like figures and axons degenerate. The
      mutation leads to an abnormal regulation of some, but not all, molecules involved
      in myelination. These results demonstrate that P0 is essential for the normal
      spiraling, compaction, and maintenance of the peripheral myelin sheath and the
      continued integrity of associated axons. They further suggest that this protein
      conveys a signal that regulates Schwann cell gene expression.

PMID- 1384989
TI  - The reverse transcriptase of hepatitis B virus acts as a protein primer for viral
      DNA synthesis.
AB  - Hepatitis B viruses (hepadnaviruses) replicate their DNA genomes by reverse
      transcription of an RNA intermediate. Efforts to examine the biochemical
      mechanism for viral DNA synthesis have been hampered by the failure to solubilize
      the reverse transcriptase from virions and to express the polymerase in
      heterologous systems in an enzymatically active form. Here, we demonstrate that
      the polymerase of a hepadnavirus synthesized in an in vitro translation reaction
      exhibits reverse transcriptase activity. Furthermore, our results show that the
      polymerase acts as a primer for DNA synthesis and remains covalently linked to
      nascent DNA, a feature that is not known to exist in any other RNA-directed DNA
      polymerases. Priming of DNA synthesis requires viral RNA but occurs independently
      of other viral components. The ability to express the hepadnavirus reverse
      transcriptase in an enzymatically active form will allow detailed biochemical and
      functional analyses of this complex enzyme, and may facilitate the identification
      of inhibitors required for antiviral therapy.

PMID- 1384990
TI  - The pro region of BPTI facilitates folding.
AB  - The in vitro folding pathway of bovine pancreatic trypsin inhibitor (BPTI) has
      been described previously in terms of the disulfide-bonded intermediates that
      accumulate during folding of the protein. Folding is slow, occurring in hours at
      pH 7.3, 25 degrees C. In addition, approximately half of the BPTI molecules
      become trapped as a dead-end, native-like intermediate. In vivo, BPTI is
      synthesized as a precursor protein that includes a 13 residue amino-terminal pro
      region. This pro region contains a cysteine residue. We find that, in vitro, both
      the rate of formation and the yield of properly folded BPTI are increased
      substantially in a recombinant model of pro-BPTI. The cysteine residue is
      necessary for this effect. Moreover, a single cysteine residue, tethered to the
      carboxy-terminal end of BPTI with a flexible linker of repeating Ser-Gly-Gly
      residues, is sufficient to assist in disulfide formation. Thus, the pro region
      appears to facilitate folding by providing a tethered, solvent-accessible,
      intramolecular thiol-disulfide reagent.

PMID- 1384991
TI  - Activation of T cells through a T cell-specific epitope of CD45.
AB  - The 180- and 190-kDa isoforms of CD45 are preferentially expressed on the helper
      inducer (memory) subset of CD4 cells. In order to generate monoclonal antibodies
      against the extracellular domains of these isoforms and determine whether they
      could regulate the function and activation of these cells, we developed a mAb,
      anti-4H2D, by immunizing Balb/c mice with an isogenic mouse pre-B cell line
      expressing the human 190-kDa CD45 isoform. Anti-4H2D reacts with approximately
      60% of T cells, 70% of CD4 cells, and 60% of CD8 cells. The CD4 cell population
      defined by this mAb corresponds functionally and phenotypically to that defined
      by the CD45RO+CD29+ subset. Western blotting demonstrated that anti-4H2D reacts
      primarily with the 190-kDa isoform of CD45 and to a minor extent, the 205- and
      180-kDa CD45 isoforms. Interestingly, this mAb reacted with only a subpopulation
      of mature thymocytes and peripheral T cells, despite the fact that the 190-kDa
      CD45 isoform, as well as CD45RO and CD29, is more widely distributed on cells of
      hematopoietic origin. The 4H2D epitope was neuraminidase sensitive, indicating
      that anti-4H2D reacts with a carbohydrate epitope which is present on only a
      subset of the T cells containing the 190-kDa CD45 isoform epitopes. Functional
      studies showed that soluble anti-4H2D augmented T cell proliferation induced by
      the CD2 and CD3 pathways, and treatment of T cells with this mAb up-regulated
      [Ca2+]i flux induced by both anti-CD2 and anti-CD3 mAbs. These results suggest
      that the 190-kDa CD45 isoform on human CD4 cells is heterogeneous and that the
      190-kDa isoform recognized by anti-4H2D regulates the function and activation of
      CD4 helper T cells.

PMID- 1384992
TI  - IL-1-induced prostacyclin production by cerebral vascular endothelial cells
      inhibits myelin basic protein-specific lymphocyte proliferation.
AB  - Addition of cerebral vascular endothelial cells (EC) to myelin basic protein
      (MBP) immune lymph node cells (LNC) cultured in the presence of MBP resulted in
      the inhibition of MBP-specific proliferative responses. Proliferation was not
      inhibited in cultures containing indomethacin (IM), suggesting a possible role
      for prostaglandins. Significant levels of 6-KPGF1 alpha, the stable hydrolysate
      product of PGI2, but not PGE2 were observed in culture (LNC + EC) supernatants
      but not in supernatants from cultures containing only LNC or EC. The levels of
      PGI2 release were proportional to the concentration of exogenous EC present in
      culture and synthesis of PGI2 could be blocked by IM. These results indicate the
      requirement for coculture in the generation PGI2. Additional experiments
      indicated that EC were required for the generation of PGI2 and that either
      macrophages (M phi), or recombinant murine IL-1 were able to replace LNC in
      cocultures with EC in order to generate PGI2. The ability of IL-1 to stimulate EC
      derived PGI2 synthesis was dose dependent with maximal stimulation observed at 50
      U/ml IL-1. The IL-1-induced production of PGI2 by EC as well as PGI2 production
      in cultures containing EC and either LNC or M phi was inhibited by treatment with
      anti-IL-1 antibody. These results indicate that EC are capable of inhibiting
      antigen-specific lymphocyte proliferation by producing PGI2, which can be induced
      by the lymphokine, IL-1.

PMID- 1384993
TI  - The pp60c-src in retinal pigment epithelium and its modulation by vasoactive
      intestinal peptide.
AB  - The pp60c-src is present at high level in differentiated retinal pigment
      epithelium (RPE) in culture. Immunofluorescence microscopy using GD11 (anti-pp60c
      src) shows intense staining in the plasma membrane, especially at the cell-cell
      junctions, and diffuse staining in the cytoplasma. Western blot analysis shows
      that the majority of the GD11-reactive molecules is localized in the membrane.
      The pp60c-src does not translocate between membrane and cytoplasma when the RPE
      was reacted with vasoactive intestinal peptide (VIP), which is previously shown
      to stimulate phosphorylation of the pp60c-src in the membranes (Biochem. Biophys.
      Res. Commun. 174, 452-8, 1991). Here, VIP modulation is shown to alter the
      reactivity of pp60c-src with a monoclonal anti-phosphotyrosine antibody.

PMID- 1384994
TI  - Pathogenesis of myelin breakdown in demyelinating diseases: role of proteolytic
      enzymes.
AB  - The mechanism by which the myelin sheath is degraded in demyelinating diseases is
      unknown. The demonstration of increased activities of both acid (cathepsins B, D,
      A) and neutral proteinases in tissue from experimental allergic encephalomyelitis
      (EAE) in animals and multiple sclerosis (MS, plaques) and the disappearance of
      myelin proteins implicate a role for proteolytic enzyme in myelin breakdown. The
      degradation of myelin basic protein (MBP) by proteinase yields encephalitogenic
      peptides and its loss has been found to cause structural alteration of the myelin
      sheath. This suggests that MBP degradation is an initial step in the breakdown of
      myelin in demyelinating diseases. A calcium-activated neutral proteinase
      (calpain), which degrades MBP, was found to increase in activity in MS tissue and
      cerebrospinal fluid (CSF), and its presence in myelin suggests that myelin may be
      autodigested in demyelinating disease. The source of increased proteinase
      activity has been indicated as macrophages, lymphocytes, and proliferative
      astrocytes (reactive cells). Increased proteinase activity is found in Schwann
      cells in Wallerian degeneration, and the presence of calpain in myelin-forming
      oligodendrocytes and Schwann cells suggests that these cells are likely sources
      of degradative enzymes. The involvement of proteolytic enzymes in the mechanism
      of myelin breakdown indicates the possible intervention with proteinase
      inhibitors for beneficial effect.

PMID- 1384995
TI  - Transformation of Cochliobolus lunatus with pUT 720 changes the steroid
      hydroxylating ability of the fungus.
AB  - The filamentous fungus Cochliobolus lunatus, a known 11 beta-hydroxylator of
      steroids, was transformed to bleomycin resistance using the heterologous plasmid
      pUT 720. This plasmid contains the Sh ble gene expressed under the control of the
      Aspergillus nidulans gpd and trpC expression signals. The bleomycin-resistant
      colonies appeared with a frequency of six per microgram of DNA. All colonies were
      real transformants and no "abortive" growth was observed. In all transformants
      tested the plasmid molecules became stably integrated into the genome of the
      host, and one of the plasmid molecules integrated in a site-specific manner.
      Transformants retained the ability to hydroxylate the steroid ring, but the
      hydroxy group was inserted at the 15 alpha position.

PMID- 1384996
TI  - RNA editing in the mitochondria of a conifer.
AB  - A 712-base portion of the mitochondrial gene coxI and the corresponding portion
      of the coxI transcript were amplified by PCR and by RT-PCR, respectively, from
      the gymnosperm western red cedar. Sequence comparison of amplified coxI DNA and
      mRNA revealed 26 C-to-U differences that are best explained by RNA editing of the
      type known to occur in angiosperms. This finding suggests that mitochondrial RNA
      editing of the C-to-U type arose before the divergence of gymnosperms and
      angiosperms and can be considered a feature common to all higher plants.

PMID- 1384997
TI  - Removal of endotoxin from culture supernatant of Bordetella pertussis with
      aminated poly(gamma-methyl L-glutamate) spherical beads.
AB  - Attempts were made to prepare adsorbents having a high affinity for endotoxin in
      the culture supernatant of Bordetella pertussis. When poly(gamma-methyl L
      glutamate) (PMLG) was used as a matrix and amino groups as the ligand, the
      highest affinity for endotoxin was attained even at a high ionic strength (mu =
      0.2-0.4). PMLG beads containing amino groups of about 3.2 meq/g selectively
      removed endotoxin from the culture supernatant of B. pertussis without affecting
      the protective antigens. It was demonstrated that 1 ml of the wet adsorbent
      adsorbed 4.5 mg of endotoxin. The beads of PMLG derivatives, therefore, are
      considered to be a useful adsorbent for the removal of endotoxin from the
      pertussis vaccine, affecting neither filamentous hemagglutinin nor pertussis
      toxin.

PMID- 1385000
TI  - Effect of cAMP elevating compounds on inhibition of gap junctional communication
      and induction of morphological transformation in Syrian hamster embryo cells.
AB  - An enhancement of the cellular cAMP level has been shown to protect against
      phorbol ester-induced inhibition of gap junctional intercellular communication
      (GJIC) and induction of morphological transformation in Syrian hamster embryo
      (SHE) cells. Cholera toxin, forskolin, 3-isobutyl-1-methylxanthine (IBMX) and
      theophylline counteracted the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      inhibition of GJIC. The enhancement of communication by these compounds was
      independent of the TPA concentration, as well as whether the cells were treated
      with TPA prior to or after the cAMP elevating agents. The induced increase in the
      cAMP level by cholera toxin occurred in the same concentration range as the
      enhancement of GJIC. With forskolin the effect on GJIC was apparent at
      concentrations 10 times lower than needed to enhance the cAMP level. IBMX and
      theophylline were found to enhance GJIC with only a 20% elevation of cAMP. The
      cAMP elevating compounds also suppressed the response of TPA on induction of
      transformed morphology in SHE cells.

PMID- 1384999
TI  - Photoactivation of 2-nitrofluorene in vitro and in the rat in vivo. UVA-induced
      formation of reactive intermediates that bind covalently to RNA and protein.
AB  - 2-Nitrofluorene (2-NF), an environmental pollutant, can be activated by UV light
      to reactive intermediates that bind covalently to RNA and protein in vitro: high
      levels of covalent binding were obtained. This covalent binding was not dependent
      on the presence of oxygen in the solution and could be decreased by glutathione.
      Hydrolysis of the in vitro modified RNA and subsequent analysis of the liberated
      bases by HPLC revealed that approximately 15% of the covalent binding of 2-NF to
      RNA could be attributed to the formation of a guanosine adduct of nitroreduced 2
      NF, N-(deoxyguanosin-8-yl)-2-aminofluorene. Many other adducts are formed of
      which the structure and mechanism of formation are as yet unknown. The
      possibility of photoactivation of 2-NF in the rat in vivo was also investigated.
      Photoactivation increased covalent binding of 2-NF in the skin but not in other
      organs. The mechanism of the photoactivation of 2-NF is discussed.

PMID- 1385001
TI  - Purification and analysis of glycoproteins bearing blood group-A determinants
      from hamster pancreatic ductal adenocarcinomas.
AB  - Although the hamster pancreas does not express A, B or H blood group antigens,
      all hamster pancreatic ductal adenocarcinomas induced by treatment with N
      nitrosobis(2-oxopropyl)amine express blood group-A antigen. Thus, the acquisition
      of blood group-A antigen expression in this system is a cancer-associated
      alteration. We have purified three major blood group-A antigen bearing
      glycoproteins (gp120, gp135 and gp150) from hamster pancreatic cancer cell
      membrane preparations using affinity chromatography on DBA (Dolichos biflorus)
      agglutinin-agarose. When assayed by immunoblotting, gp120 and gp135 showed strong
      blood group-A reactivity, which was removed by treating membrane samples with
      peptide-N-glycosidase F. Blood group-A reactivity was unchanged by treatment of
      the membrane fractions with endoglycosidases F and H. In addition, these two
      glycoproteins bearing blood group-A antigen also bound L-PHA (Phaseolus vulgaris
      leucoagglutinin). These results demonstrate that gp120 and gp135 express blood
      group-A antigen on Asn-linked multi-antennary complex type glycan structures. The
      gp150 showed weak blood group-A expression. This is the first demonstration of
      the neoexpression of cancer-associated blood group-A determinants which reside on
      Asn-linked glycan structures.

PMID- 1385002
TI  - Non-promoting 12-deoxyphorbol 13-esters as potent inhibitors of phorbol 12
      myristate 13-acetate-induced acute and chronic biological responses in CD-1 mouse
      skin.
AB  - In previous experiments, pretreatment of CD-1 mouse skin with prostratin (12
      deoxyphorbol 13-acetate) inhibited hyperplasia, induction of ornithine
      decarboxylase and edema in response to acute treatment with phorbol 12-myristate
      13-acetate (PMA). We report here that prostratin inhibits biological responses
      induced by multiple (chronic) PMA treatment. A typical chronic treatment schedule
      consisted of five applications of 3.2 nmol (2 micrograms) PMA at 48 h intervals.
      Most effective inhibition could be achieved when the first PMA treatment was
      preceded 48 h before by a lower dose of prostratin (256 nmol = 100 micrograms)
      and each PMA treatment was preceded 15 min before by a higher dose (2.56 mumol =
      1 mg) of prostratin. Under this schedule hyperplasia was completely blocked, as
      was keratin K6 expression (a marker of hyperproliferative epidermis), whereas
      myeloperoxidase activity (a marker of neutrophil granulocyte infiltration) was
      reduced to 36%. 12-Deoxyphorbol 13-phenylacetate (dPP), a non-promoting 12
      deoxyphorbol derivative that binds to protein kinase C with two orders of
      magnitude higher potency than does prostratin, showed the same pattern of
      inhibition as did prostratin for a single PMA treatment but with a corresponding
      two orders of magnitude higher potency. In the case of chronic PMA treatment,
      however, dPP failed to inhibit hyperplasia fully, though it reduced keratin K6
      expression and inflammation. Dissociation of K6 expression from hyperplasia was
      unexpected, since expression of these two responses was thought to be closely
      coupled. We conclude that 12-deoxyphorbol 13-monoesters are functional
      antagonists for a class of protein kinase C-mediated responses closely correlated
      to tumor promotion.

PMID- 1384998
TI  - Thrombospondin as a mediator of cancer cell adhesion in metastasis.
AB  - Thrombospondin (TSP) is a 450 kDa adhesive glycoprotein. It is present in high
      concentrations in the platelet alpha-granule and can readily be secreted
      following platelet activation where local concentrations can be increased by 3-4
      orders of magnitude. TSP is also synthesized by a variety of other cells and is
      incorporated into their extracellular matrix. TSP is a homotrimer with a number
      of functional domains, at least four of which might serve as receptor recognizing
      regions. The amino-terminal heparin binding domain interacts with heparin, other
      glycosaminoglycans and glycolipids and likely recognizes specific cell surface
      proteoglycans. The central disulfide cross-linked region, 210 kDa non-reduced and
      70 kDa reduced, contains a peptide motif CSVTCG which is apparently responsible
      for binding to glycoprotein IV (CD36) with high affinity. Immediately adjacent to
      the calcium binding region of TSP, which undergoes considerable molecular
      relaxation in the absence of calcium, is an RGDA sequence. TSP has been
      demonstrated to bind to integrins of the alpha v beta 3 and alpha IIb beta 3
      class. The carboxy-terminal region of TSP also contains at least one binding
      epitope for a cell receptor. There are 2 well characterized genes for TSP and
      truncated forms of TSP have been detected which have inhibitory effects on
      angiogenesis. Finally, TSP can interact with fibrinogen and fibronectin, perhaps
      on cellular surfaces, which might serve as secondary receptor-like mechanisms for
      TSP binding and subsequent mediation of cell adhesion.

PMID- 1385004
TI  - Prostaglandin D2 relaxes bovine coronary arteries by endothelium-dependent nitric
      oxide-mediated cGMP formation.
AB  - This study investigates the vasomotor activities of prostaglandin (PG) D2 in
      bovine coronary arteries in relation to endothelial function. Isolated segments
      of bovine coronary arteries with intact endothelium were concentration
      dependently relaxed by PGD2 (0.01-1 microM), a reaction that was blocked by a
      selective PGD receptor antagonist (BW A868C). There was a tight correlation
      between PGD2- and acetylcholine-induced relaxations (r = 0.894, n = 96, p <
      0.001). Removal of endothelium abolished the PGD2-induced relaxation and unmasked
      a contractile activity of the compound. Inhibition of endogenous PGI2 formation
      by indomethacin did not modify these responses, whereas inhibition of endogenous
      nitric oxide generation by NG-nitro-L-arginine and NG-monomethyl L-arginine (10
      or 100 microM) or scavenging of released nitric oxide by oxyhemoglobin (3 microM)
      considerably (> 50%) antagonized the PGD2-induced relaxation. The vessel
      relaxation by PGD2 was associated with a threefold to fourfold increase in
      vascular cGMP. A considerable reduction in vascular cGMP was measured after
      removal of the endothelium (by 53%) and inhibition of endogenous nitric oxide
      generation by NG-nitro-L-arginine (by 70%). This also resulted in a complete
      inhibition of PGD2-induced cGMP accumulation. Similar results were obtained with
      the stable PGD2 mimetic ZK 110.841, suggesting that these biological activities
      of PGD2 were due to the compound itself and not caused by any PGD2 metabolite. A
      slight but significant increase in cAMP was observed in arteries with intact
      endothelium as well as after removal of endothelium. Because the relaxing effect
      of PGD2 was strictly endothelium dependent, the observed relaxation cannot be
      explained by cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385003
TI  - Studies on the relationship between xanthine oxidase and histamine release during
      intestinal ischemia-reperfusion.
AB  - Recent studies have demonstrated a connection between xanthine oxidase-generated
      reactive oxygen intermediates and histamine release during ischemia-reperfusion.
      In the present work, the effect of modulation of the endogenous histamine level
      on the xanthine oxidase activity was examined during the reperfusion of a canine
      ileal segment following a 2 hr of complete ischemia. The xanthine oxidase
      activity and the plasma histamine level peaked simultaneously at the beginning of
      reperfusion, reaching mean values of 14.9 nmol/ml/min and 12.1 nmol/l,
      respectively. Pretreatment with aminoguanidine, a blocker of diamine oxidase
      (histaminase), resulted in significantly higher levels of histamine during
      reperfusion, but this elevation was not accompanied by a further increase in
      xanthine oxidase activity. Pretreatment with the mast cell stabilizer cromolyn
      significantly diminished the rise in plasma histamine level, with an unchanging
      activity of xanthine oxidase. No significant alteration could be observed in the
      postocclusive activity of xanthine oxidase following the intra-arterial
      administration of 0.5, 1, or 5 nmol of histamine during the last 10 min of the
      ischemic period. These data suggest that the amount of histamine liberated during
      reperfusion does not result in a further increase in the xanthine oxidase
      activity. The release of histamine is not a cause, but rather an effect of the
      elevated activity of intestinal xanthine oxidase.

PMID- 1385005
TI  - Proto-oncogene expression in porcine myocardium subjected to ischemia and
      reperfusion.
AB  - The molecular basis of myocardial adaptation to ischemia and reperfusion is
      poorly understood. It is thought that nuclear proto-oncogenes act as third
      messengers, converting cytoplasmic signal transduction into long-term changes of
      gene expression. We studied the expression of six nuclear proto-oncogenes (Egr-1,
      c-fos, fosB, c-jun, junB, and c-myc) in myocardium subjected to ischemia and
      reperfusion in anesthetized pigs. Stunning was achieved by two 10-minute left
      anterior descending coronary artery occlusions separated by 30 minutes of
      reperfusion. Hearts were excised after the first occlusion, after the first
      reperfusion, and at 30, 120, 150, and 210 minutes of reperfusion after the second
      occlusion. Total RNA was prepared from stunned as well as normally perfused
      myocardial tissue and subjected to Northern blotting. The response of the six
      nuclear proto-oncogenes varied.fosB gene expression was never detected. The c-myc
      gene was expressed, but its level was unchanged by ischemia. c-jun expression was
      slightly increased by ischemia (3.1 +/- 0.6-fold). The c-fos, Egr-1, and junB
      genes were highly induced, being fivefold to sevenfold higher in experimental
      than in control tissue. In three animals pretreated with the beta 1-antagonist
      metoprolol and then subjected to the above experimental protocol, the induction
      of proto-oncogenes was similar to that in nonblocked controls. Our results show
      that the myocardial adaptive response to ischemic stress includes the induction
      of at least four transcription factors that may be further operative in repair
      processes and angiogenesis.

PMID- 1385006
TI  - Nitric oxide synthase in cardiac nerve fibers and neurons of rat and guinea pig
      heart.
AB  - Participation of nitric oxide (NO) in the autonomic innervation of rat and guinea
      pig hearts was investigated by applying the NADPH diaphorase technique and
      immunohistochemistry with NO synthase antiserum. We present evidence that NO
      synthase is localized in cardiac ganglion cells and nerve fibers innervating the
      sinuatrial and atrioventricular nodes, the myocardium, local neurons, coronary
      arteries, and pulmonary vessels, suggesting an involvement of NO in neurogenic
      heart rate regulation, myocardial cell function, neuronal transmission in cardiac
      ganglia, and coronary as well as pulmonary vasodilation.

PMID- 1385007
TI  - Fontan procedure for hypoplastic left heart syndrome.

PMID- 1385008
TI  - Course in the intensive care unit after 'preparatory' pulmonary artery banding
      and aortopulmonary shunt placement for transposition of the great arteries with
      low left ventricular pressure.
AB  - BACKGROUND: In patients with transposition of the great arteries with low left
      ventricular pressure, pulmonary artery banding with aortopulmonary shunt
      placement has been advocated to "prepare" the left ventricle for systemic work
      before an arterial switch operation. METHODS AND RESULTS: In 28 patients, this
      preparatory procedure was performed with one death. A successful arterial switch
      operation was performed at a median of 7 days later in 24 of 27 survivors; one
      child had a Senning performed, and two others died. During this interval period,
      the left ventricular-to-right ventricular pressure ratio increased from 48 +/- 8%
      to 98 +/- 19%, and left ventricular mass (indexed for body surface area)
      increased from 46 +/- 17 to 72 +/- 23 g/m2. After the preparatory procedure, the
      initial postoperative period was frequently characterized by a low-output
      syndrome of variable length and severity. Prolonged mechanical ventilation,
      extended inotropic support, and/or a significant metabolic acidosis was present
      in 21 of 28 patients in the immediate postoperative period. CONCLUSIONS: The low
      output syndrome is most likely due to a combination of acute (fixed) right
      ventricular volume overload from the shunt and acute (transient) left ventricular
      dysfunction from the pulmonary artery band. This low-output syndrome should be
      anticipated following the preparatory procedure.

PMID- 1385009
TI  - Results of a right ventricular outflow patch for pulmonary atresia with intact
      ventricular septum.
AB  - BACKGROUND: Although overall outcome has improved, pulmonary atresia with intact
      septum remains a difficult surgical and clinical problem. To determine whether an
      early right ventricular outflow patch will result in biventricular repair for
      this lesion, we reviewed the long-term follow-up (5.8 +/- 0.8 years) of 19
      newborns who underwent repair between 1979 and 1990. METHODS AND RESULTS: An
      early right ventricular outflow patch was placed in 15 of 19 newborns; in the
      remaining four, this was preceded by an aortopulmonary shunt. Prostaglandin E1
      infusion postoperatively eliminated the need for shunt in 14 of 15. Coronary
      sinusoids were ligated in three newborns. Based on right ventricular morphology,
      the newborns were divided into two groups: group 1 (tripartite, n = 9) and group
      2 (bipartite and monopartite, n = 10). Before surgery, group 1 had significantly
      larger right ventricular volumes (23.6 +/- 3.7 versus 5.2 +/- 1.1 ml/m2, p <
      0.002). Five-year survival was 79% for the entire series. Four infants, all group
      2, died within 12 months of their initial surgery. Fourteen of 15 survivors (nine
      group 1 and five group 2) currently are acyanotic and New York Heart Association
      functional class I. A biventricular repair was achieved in 12 of 15, and three
      other children are awaiting evaluation. All 15 survivors had significant right
      ventricular and tricuspid annulus growth. CONCLUSIONS: Our data suggest that
      early placement of a right ventricular outflow patch in infants with pulmonary
      atresia and intact ventricular septum, regardless of right ventricular anatomy,
      results in an excellent chance for biventricular repair.

PMID- 1385010
TI  - Aprotinin prevents cardiopulmonary bypass-induced platelet dysfunction. A
      scanning electron microscope study.
AB  - BACKGROUND: Administration of aprotinin during extracorporeal circulation reduces
      blood loss and improves platelet function. METHODS AND RESULTS: To evaluate the
      protective effect of aprotinin on platelets, 50 patients undergoing
      cardiopulmonary bypass were randomized before surgery to one of three groups.
      Seventeen patients (group A) received continuous high-dose aprotinin (7 x 10(6)
      KIU) during cardiopulmonary bypass, 17 (group B) received a single bolus of
      aprotinin in the pump prime (2 x 10(6) KIU), and 16 (group C) received placebo.
      Scanning electron microscopy was used to evaluate platelet aggregation on
      extracellular matrix. The platelet function was graded from 1 to 4, with grade 4
      being normal aggregation. Immediately after cardiopulmonary bypass, 16 patients
      in group A (94%) reached preoperative aggregation grade (mean grade, 3.4 +/- 0.7)
      compared with nine of 17 in group B (52%) (mean grade, 2.9 +/- 1.2), and none in
      group C (0%) (mean grade, 1.4 +/- 0.5; p < 0.001). Postoperative platelet count
      did not differ significantly among the three groups. After surgery, group A bled
      less than groups B and C (395 +/- 120 versus 488 +/- 135 and 780 +/- 408 ml,
      respectively; p < 0.01). Patients in the aprotinin groups received fewer red
      blood cell units (0.9 +/- 1.2 and 1.9 +/- 1.2 versus 3.4 +/- 1.9, respectively; p
      < 0.01) and were exposed to less homologous blood products (1.3 +/- 1.7 and 2.1
      +/- 1.1 versus 6.1 +/- 5, respectively; p < 0.001). CONCLUSIONS: By preserving
      platelet function, aprotinin improves postoperative hemostasis in all patients
      who receive high dose and in most who receive low dose.

PMID- 1385011
TI  - Aprotinin and heparin monitoring during cardiopulmonary bypass.
AB  - BACKGROUND: When high-dose aprotinin is used during cardiopulmonary bypass, there
      is a prolongation of the activated coagulation time (ACT), which is used to
      monitor heparinization. The aim of this study was to provide guidelines for
      monitoring heparin levels by the ACT if aprotinin is used during cardiopulmonary
      bypass. METHODS AND RESULTS: Heparinized blood from six healthy controls and nine
      patients on cardiopulmonary bypass was aliquoted and mixed with various
      concentrations of aprotinin. ACTs were performed on these samples. Activated
      partial thromboplastin times (APTT) were performed on the citrated plasma mixed
      with varying concentrations of heparin and aprotinin from the same control
      patients. Prothrombin times (PT) were performed on plasmas mixed with aprotinin.
      Aprotinin produced a dose-related prolongation of ACT and APTT but had no effect
      on PT. This effect occurred whatever the activating agent and in the absence of
      heparin. CONCLUSIONS: Aprotinin prolongs the ACT and APTT independently of
      heparin. If high-dose aprotinin is used during cardiopulmonary bypass, ACTs
      should be maintained at times > 750 seconds to allow for appropriate levels of
      heparin.

PMID- 1385012
TI  - Viral hepatitis in the 1990s, Part III: Hepatitis C, hepatitis E, and other
      viruses.
AB  - Acute hepatitis can be caused by a number of viruses, especially A, B, C, E,
      delta, Epstein-Barr virus, and cytomegalovirus. Hepatitis A and B have been
      discussed previously in this series. The virus responsible for most cases of what
      commonly has been referred to as non-A non-B hepatitis has been tracked, and
      antibodies to certain proteins of this virus have been identified. This virus is
      now referred to as hepatitis C. The possible clinical outcomes after acute
      hepatitis C virus infection are similar to those for hepatitis B virus infection,
      except that hepatitis C is far more likely to become chronic. Clinical testing
      for hepatitis C virus infection is in its infancy and has certain limitations.
      Successful treatment of at least some cases of hepatitis C is possible. Hepatitis
      E has recently been described, primarily in third-world countries. It causes an
      acute hepatitis that may be particularly lethal for pregnant women. Herpesviruses
      may also cause hepatitis, particularly in the newborn or the immunocompromised.
      Exotic viruses causing acute hepatitis are enumerated.

PMID- 1385013
TI  - Development of peptide- and tyrosine hydroxylase-containing neurons in the fetal
      spinal cord transplanted into the anterior chamber of the eye of adult rats.
AB  - Fetal rat spinal cord transplanted into the anterior chamber of the eye of an
      adult rat was immunohistochemically stained using antisera to substance P (SP),
      neuropeptide Y (NPY), methionine-enkephalin (ENK), vasoactive intestinal
      polypeptide (VIP), calcitonin gene-related peptide (CGRP) and tyrosine
      hydroxylase (TH), and distributional changes of peptide- and enzyme-containing
      neurons 1, 2 and 4 weeks after transplantation were investigated. To examine the
      effect of colchicine on immunoreactivity, unilateral eyes of these adult host
      rats received intraocular colchicine treatment. Without colchicine treatment,
      numerous SP- and CGRP-immunoreactive (IR) neurons were observed in the graft 1
      week after transplantation, and their immunoreactivity gradually decreased up to
      4 weeks after transplantation. NPY-, ENK-and VIP-IR neurons first appeared in the
      graft 2 weeks after transplantation. Four weeks after transplantation, the
      immunoreactivity of NPY and ENK decreased significantly, whereas VIP-IR neurons
      showed the same intensity as that observed at 2 weeks after transplantation. TH
      IR neurons, on the other hand, were seen at every stage, but their
      immunoreactivity was constant all the time. After colchicine treatment, the
      number of SP-, NPY-, ENK- and CGRP-IR neurons appeared to increase, while that of
      VIP- and TH-IR neurons did not change significantly. The distribution patterns of
      the peptide- and enzyme-containing fibers differed from each other. In the
      analysis of serial sections stained with 5 peptides (SP, NPY, ENK, VIP, CGRP),
      fibers containing these peptides were found to be densely accumulated in specific
      areas of the transplanted spinal cord. The present findings demonstrated that
      most of the peptide- and enzyme-containing neuron systems in the transplanted
      spinal cord showed similar distribution patterns and development to those in the
      normal spinal cord, but that some displayed different distribution.

PMID- 1385014
TI  - Influence of position along the medial-lateral axis of the superior colliculus on
      the topographic targeting and survival of retinal axons.
AB  - Topographic order in the rat retinocollicular projection emerges from an
      initially diffuse projection during an early postnatal remodeling period that is
      coincident with the period of naturally occurring ganglion cell death. Here, we
      examine the relationship between a retinal axon's position along the medial
      lateral axis as it enters the superior colliculus (SC) and its ability to form an
      appropriately positioned arbor and survive the remodeling period. At E18-E19,
      prior to map remodeling, axons labeled with focal DiI injections in the periphery
      of temporal, nasal, superior or inferior retina are widespread along the medial
      lateral SC axis. At P12, after remodeling, the distributions of axons remain
      widespread over the medial-lateral SC axis relative to the positioning of their
      terminal arborizations, and resemble the distributions labeled at E18-E19, with
      the exception that the small proportion of axons most widely mispositioned along
      the medial-lateral SC axis are less frequent. These data indicate that the most
      widely mispositioned retinal axons are preferentially eliminated, but that a high
      proportion of retinal axons mispositioned along the medial-lateral axis as they
      enter the SC can correct their position, form topographically appropriate arbors,
      and survive the remodeling period.

PMID- 1385015
TI  - Expression of thyroid hormone receptors mRNAs in rat cerebral hemisphere neuronal
      cultures.
AB  - We have studied the expression of the alpha and beta thyroid receptors mRNAs (TR
      mRNAs) in cerebral hemisphere neuronal cultures, initiated from 15-day-old rat
      embryos, by northern analysis. In the cultures grown in the absence of L
      triiodothyronine (L-T3), the alpha 2 TR-mRNAs were the predominant form of TR
      mRNAs and were approximately 8 to 20-fold higher than the levels of the alpha 1
      TR-mRNAs, depending on the age of the cultures. The levels of alpha 2 TR-mRNAs
      significantly increased by 1.8 fold between day 8 and 15 and remained on a
      plateau value thereafter until day 22. Over the same time period, there were no
      significant changes on the levels of alpha 1 TR-mRNAs. The ratio alpha 1/alpha 1
      + alpha 2 TR-mRNAs decreased between day 8 and 15. The beta 1 TR-mRNAs increased
      by 8 fold between day 8 and day 22. On day 8, the beta 1 TR-mRNAs were 1.8 fold
      lower than the levels of the alpha 1 TR-mRNAs while they were 6 fold higher on
      day 22. L-T3 treatment of the cultures had no effect on the levels of the alpha
      1, alpha 2 and beta 1 TR-mRNAs. The differential temporal expression of the alpha
      1 and beta 1 TR-mRNAs suggests distinct functions for both types of T3 receptors
      in neuronal maturation.

PMID- 1385016
TI  - Characterization of a novel set of membrane antigens associated with axonal
      growth. I. Biochemical and functional studies.
AB  - Cranin, a prominent 120 kDa laminin-binding protein of cell membranes, was
      originally identified and characterized by virtue of its ability to bind laminin
      directly in ligand-blotting assays. We have now raised polyclonal ('3070') and
      monoclonal antibodies (MAbs 4 and 199) against a partially purified preparation
      of cranin, and have characterized the properties and expression of the
      corresponding antigens in further detail. In immunoblots of E14 chick brain
      membranes, these antibodies all recognized a single major band migrating at
      approximately 125 kDa, with minor bands at 115 kDa and 170/180 kDa. The major 125
      kDa antigen bound to laminin affinity beads in a divalent cation- and
      conformation-dependent manner. The 125 and 115 kDa bands were also the most
      prominent HNK-1 positive proteins detected overall within E14 chick brain
      membranes. MAbs 4 and 199 specifically inhibited the attachment of NG108-15 cells
      to low, but not high amounts of substratum-bound laminin. While the relation of
      3070/MAb 4 antigens to cranin requires further elucidation, these data, together
      with evidence presented in the companion papers and elsewhere, suggest that the
      antigens are important in neural development by mediating at least some of the
      responses of neural cells to laminin--for example, by acting as a laminin
      receptor guiding axonal outgrowth and neuronal migration, or by involvement in
      the transport and binding of laminin to the surface of neurons and reactive glial
      cells that synthesize laminin.

PMID- 1385017
TI  - Two-site immunoradiometric assay of intact salmon calcitonin.
AB  - We developed a two-site immunoradiometric assay (IRMA) of salmon calcitonin (SCT)
      that detects intact SCT(1-32) and not peptide fragments of the hormone. This was
      accomplished by using monoclonal antibodies prepared against the peptide
      fragments SCT(1-11) and SCT(11-32). Two antibodies with specificity for each of
      the peptides were purified from their respective ascites and evaluated in a two
      site format wherein one of the antibodies was adsorbed to polystyrene beads and
      the other was radioiodinated. In this assay format, the antibody pair detected
      intact SCT(1-32) but did not react with either SCT(1-11) or SCT(11-32). The
      sensitivity of the assay could be increased by exchanging the antibodies with
      respect to bead adsorption and radioiodination. Furthermore, by increasing the
      incubation time and volume of incubation of sample with the polystyrene-bead
      adsorbed antibody, the effective detection limit of the assay could be improved.
      This assay system can be used to detect intact SCT when the presence of fragments
      of the hormone might otherwise complicate interpretation of assay data.

PMID- 1385018
TI  - Clinical evaluation of a pancreatic lipase mass concentration assay.
AB  - An immunoactivation assay for determining pancreatic lipase mass concentration
      was clinically evaluated and compared with results obtained by measuring total
      amylase and pancreatic amylase activity. A group of 30 patients with pancreatitis
      was compared with a control group of 32 patients in which this disease was
      suspected but excluded. Both lipase mass concentration and pancreatic amylase
      activity exhibit good sensitivity (0.93 each) and specificity (0.94 and 0.97,
      respectively) at cutoff concentrations of 200 micrograms/L and 200 U/L,
      respectively. The median increase in lipase mass concentration (37.1 times the
      upper limit of the reference interval) in the pancreatitis group was higher than
      that for either total amylase or pancreatic amylase activity (5.94 and 14.5
      times, respectively) but showed a similar time to peak value. We conclude that
      the lipase assay is the method of choice for diagnosing pancreatitis.

PMID- 1385019
TI  - Two-site assays of bone gla protein (osteocalcin) demonstrate immunochemical
      heterogeneity of the intact molecule.
AB  - We developed a panel of monoclonal antibodies to human bone gla protein (BGP;
      osteocalcin) peptides that span the linear sequence of the molecule, specifically
      BGP 1-12 (N-terminal), BGP 15-30 (midregion), and BGP 38-49 (C-terminal). These
      antibodies were evaluated in various combinations of two-site formats in studies
      of serum BGP concentrations. For clinical studies, we selected from a panel of
      antibodies the two most sensitive antibody pairs for the intact molecule (N-C);
      we also used a polyclonal RIA based on BGP-C. For the two-site format, we used
      two N-terminal antibodies, 029 and 052, adsorbed to polystyrene beads, and
      radioiodinated a C-terminal antibody, 663. The standard for each of the assays
      was purified human BGP. The following BGP serum concentrations (microgram/L, mean
      +/- SE) were measured with the various assays: by the 029-663 assay, results for
      normal subjects were 7 +/- 3, for patients with renal failure 25 +/- 8, and for
      patients with Paget disease 12 +/-4; by the 052-663 assay, the respective results
      were 22 +/- 4, 44 +/- 12, and 31 +/- 7; by the polyclonal assay, the results were
      3 +/- 0.2, 13 +/- 2, and 5 +/- 1. The two intact (N-C) assays were significantly
      (P < 0.01) correlated (r = 0.94), but their serum values differed by more than
      twofold in terms of the same BGP standard. The polyclonal assay significantly
      correlated with each of the intact assays (r = 0.83, 0.77), but it, too, gave
      different serum values for BGP. These studies demonstrate the immunochemical
      heterogeneity of circulating BGP, heterogeneity that is manifest even in
      immunoassays specific for the same region of the molecule.

PMID- 1385020
TI  - Failure of microchromatographic measurement of fetal hemoglobin in beta zero
      thalassemia-hereditary persistence of fetal hemoglobin.
AB  - We report microchromatographic measurement of fetal hemoglobin (HbF) proportions
      in a 36-year-old African-American multigravida woman. At 34 weeks she delivered a
      630-g male infant who subsequently did well. Hemoglobin electrophoresis of the
      hemolysate revealed nearly 100% HbF without HbA, an extremely unusual naturally
      occurring sample. Family studies revealed a combination of hereditary persistence
      of fetal hemoglobin (HPFH) and beta zero-thalassemia minor. Southern blot
      technique confirmed heterozygous alpha 2 thalassemia and HPFH but failed to
      identify the beta thalassemic lesion. The absence of HbA and the very high
      amounts of HbF led us to measure HbF by several methods to confirm the accuracy
      of microchromatography of HbF at values approaching 100%. HPLC revealed a 14% F1
      suggestive of microchromatographic underestimation due to glycated HbF. We
      conclude that cation-exchange microchromatography and the Betke method of alkali
      denaturation underestimate HbF values as they approach 100% and do not recommend
      these procedures in this rare situation.

PMID- 1385021
TI  - Between-lot/between-instrument variations of the Abbott IMx method for prostate
      specific antigen.

PMID- 1385022
TI  - Differences in the enzymatic nature and the sugar-chain structure of gamma
      glutamyl transferase between normal and carcinomatous human kidney and prostate.
AB  - The enzymatic and immunological nature, and the sugar chain structure, of gamma
      glutamyl transferase (GGT) purified from tissues of benign prostatic hypertrophy
      (BPH), prostatic carcinoma (PCa) and renal cell carcinoma (RCa), were compared
      with those of the normal prostate (NP) and kidney (NK). The specific activities
      of GGTs in NP, NK, BPH, PCa and RCa were 78.9, 22.5, 105, 92.5 and 52.5 mU/mg
      protein, respectively. The molecular masses of GGTs from BPH, PCa and RCa were 72
      kDa, 78 and 108 kDa, and 79 and 105 kDa, respectively. The Michaelis constants
      (Km), optimum pHs and the inhibition of GGT activities by several chemical
      compounds, revealed that the GGT from BPH, PCa and RCa was similar to that of
      normal GGT. Immunologically, the IgG fraction against anti-human seminal plasma
      GGT fused to the all of the GGTs tested. The sugar chain heterogeneities of the
      various GGTs, detected by the serial-lectin affinity technique, differed from one
      another. The sugar chain of GGT from BPH resembled the sugar chain from NP. On
      the contrary, the sugar chains of GGTs from PCa and RCa were markedly different
      from those from normal tissues. In the GGT from PCa, multi-antennary complex type
      sugar chains were more increased than the enzyme of NP. In general, as previously
      reported, the sugar chains of GGTs from carcinomatous tissues of prostate and
      kidney had an increased content of bisecting GlcNAc (beta 1-->4) containing
      complex type sugar chains. Moreover, the reductions of the biantennary complex
      type sugar chain with fucose linkage and the hybrid type sugar chain were obvious
      in the GGT from carcinomatous tissues of the prostate and kidney.

PMID- 1385023
TI  - Galanin reinstates the growth hormone response to repeated growth hormone
      releasing hormone administration in man.
AB  - OBJECTIVE: To clarify the mechanism by which galanin, a 29-amino-acid peptide,
      increases GH secretion in man. DESIGN: We studied the GH-releasing effect of this
      neurohormone (galanin, 15 micrograms/kg) infused over 60 minutes after 120
      minutes of saline, following a previous GHRH bolus (GHRH 1 microgram/kg i.v. at 0
      minutes, galanin infused from 120 to 180 minutes) and coadministered with the
      second of two consecutive GHRH boluses (GHRH every 120 minutes, galanin infused
      from 120 to 180 minutes). PATIENTS: Fourteen healthy male subjects, aged 20-34
      years, in two groups (group A, 20-31 years (n = 8); group B, 25-34 years (n = 6))
      were studied. MEASUREMENT: Blood samples were drawn every 15 minutes of 255
      minutes. Serum GH was measured in duplicate by IRMA. Statistical analysis of the
      data was carried out by non-parametric ANOVA test. RESULTS: The GH response to
      galanin infused 120 minutes after saline overlapped with that induced by the
      neuropeptide infused following previous GHRH bolus (AUC, mean +/- SEM: 317.3 +/-
      73.2 vs 326.8 +/- 54.2 micrograms/l/h). The GH-releasing effect of the second
      GHRH bolus (126.9 +/- 32.3 micrograms/l/h) was lower than that of the first one
      (503.4 +/- 41.3 micrograms/l/h; P = 0.0002). Galanin markedly enhanced the GH
      responses to the second GHRH bolus (1118.0 +/- 212.7 micrograms/l/h; P = 0.0002
      vs second GHRH bolus alone) so that it did not significantly differ from the
      first one (710.9 +/- 107.8 micrograms/l/h). CONCLUSIONS: Our results show that
      the GH-releasing effect of galanin is not modified by GHRH pretreatment and that
      the neuropeptide reinstates the GH response to the repeated GHRH stimulation in
      man. They suggest that these effects are due to the inhibition of hypothalamic
      somatostatin release.

PMID- 1385024
TI  - Effects of chronic GnRH analogue administration on gonadotrophin and alpha
      subunit secretion in post-menopausal women.
AB  - OBJECTIVE: To investigate in detail the regulation of LH, FSH, and alpha-subunit
      secretion by a GnRH agonist analogue under physiological conditions of
      gonadotrophin elevation. SUBJECTS: Six normal healthy post-menopausal women.
      DESIGN: Subjects were given D-Trp6-Pro9-Net-GnRH (GnRHa), 32 micrograms/kg,
      subcutaneously, daily for 24 days. On days 1, 2, 3, 4, 7, 11, 14, 17, 21, and 24,
      blood samples before and after GnRHa injection were taken. Sampling was continued
      off GnRHa twice a week for 4 weeks and then on days 66, 76, and 98. GnRH tests
      (100 micrograms i.v.) were performed on days 0, 24, and 98. MEASUREMENTS: All
      serum samples were analysed for LH, FSH, and alpha-subunit levels. RESULTS: LH
      and FSH levels reached a maximum on day 2 after which there was a steady decline
      to day 24. LH did not begin to rise again until day 44 (20 days off GnRHa), then
      rose steadily. FSH began to rise earlier, on day 34 (10 days off GnRHa). alpha
      Subunit levels also showed maximum elevation on day 2 but remained equally
      elevated throughout the period of GnRHa administration and then fell rapidly to
      baseline by day 34. LH, FSH, and alpha-subunit responses to i.v. GnRH were absent
      on day 24 and were equivalent to baseline on day 98. CONCLUSIONS: We conclude
      that there is a striking dissociation in the regulation of gonadotrophin and
      alpha-subunit secretion in response to GnRHa in normal post-menopausal women.
      Gonadotrophin secretion is profoundly suppressed during GnRHa administration and
      recovers only after a long delay post-treatment, while alpha-subunit is markedly
      stimulated and recovers rapidly. The difference between this pattern and that
      seen in patients with pituitary tumours could be useful for diagnosis.

PMID- 1385025
TI  - Joint manifestations in gastrointestinal diseases. 2. Whipple's disease, enteric
      infections, intestinal bypass operations, gluten-sensitive enteropathy,
      pseudomembranous colitis and collagenous colitis.
AB  - This review addresses the clinical picture of rheumatic diseases seen in
      Whipple's disease, gluten-sensitive enteropathy, pseudomembranous colitis,
      collagenous colitis and that developing after enteric infections and intestinal
      bypass operations for morbid obesity. These disorders exemplify the interplay
      between antigen entrance through the gastrointestinal canal, specific bacterial
      properties and genetic host factors such as HLA B27. In most cases such as
      interplay results in formation of circulating immune complexes causing the
      development of peripheral joint disease.

PMID- 1385026
TI  - Phenotypic analysis of lymphocyte populations in the lungs and regional lymphoid
      tissue of sheep naturally infected with maedi visna virus.
AB  - We have analysed the phenotype of lymphocytes in lung and regional lymph node of
      symptomatic and asymptomatic sheep infected with the ovine lentivirus, maedi
      visna virus (MVV). Compared to equivalent tissues from age-matched, non-infected
      controls, MVV-infected sheep show increased numbers of lymphocytes in the lung,
      both in the bronchus-associated lymphoid tissue (BALT) and in the alveolar
      septae. Both CD8+ and CD4+ T lymphocyte numbers in alveolar septae were
      increased, particularly in animals with clinical respiratory disease. The ratio
      of CD8+ to CD4+ lymphocytes was similar to that in normal lung. In both MVV
      infected and uninfected animals a high proportion of pulmonary lymphocytes,
      particularly in the alveolar septae, did not express the CD5 antigen, suggesting
      that they were activated. The number of activated cells was higher in infected
      sheep. Variable numbers of alveolar macrophages containing MVV-core protein were
      present in alveolar lumina, the majority of positive cells showing morphological
      evidence of activation. In regional lymphoid tissue there were increased numbers
      of CD8+ and gamma delta expressing T cells in lymphoid follicles and germinal
      centres of infected animals. The specificity of these cells is unknown and we
      could find no evidence for the presence of cells productively infected with the
      virus in these structures. This study shows that activated T lymphocytes,
      particularly of the CD8 subset, play a major part in the pathogenesis of MVV
      induced pulmonary and regional lymph node lesions.

PMID- 1385027
TI  - Passive immunization against tumour necrosis factor-alpha (TNF-alpha) and IL-1
      beta protects from LPS enhancing glomerular injury in nephrotoxic nephritis in
      rats.
AB  - Glomerular injury caused by injection of heterologous anti-glomerular basement
      membrane antibodies (anti-GBM Ab) is increased in rats pretreated with small
      doses of bacterial lipopolysaccharide (LPS). We have investigated the involvement
      of tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha and IL-1 beta in this
      phenomenon by passive immunization against these cytokines. Anti-TNF-alpha or
      anti-IL-1 beta antibodies given 1.5 h before the induction of nephritis
      significantly decreased injury in this model, whether assessed by the magnitude
      of albuminuria, the prevalence of glomerular capillary thrombi or the intensity
      of glomerular neutrophil infiltrate. Albuminuria in anti-GBM Ab alone was 11 +/-
      3, LPS/anti-GBM Ab 87 +/- 22, and anti-TNF-alpha antibodies/LPS/anti-GBM Ab 21 +/
      6 mg/24 h (mean +/- s.e.) P < 0.05. Passive immunization with antibodies to IL-1
      beta had a similar effect (anti-GBM Ab, 0.6 +/- 0.1, LPS/anti-GBM Ab, 92 +/- 19,
      anti-IL-1 beta antibodies/LPS/anti-GBM Ab 39 +/- 8 mg/24 h, P < 0.05). The
      prevalence of glomerular capillary thrombi was also reduced significantly by
      these treatments; from 22 +/- 5% to 4 +/- 1% in the case of anti-TNF-alpha
      antibodies and 28 +/- 5% to 13 +/- 4% with anti-IL-1 beta antibodies. Similarly,
      the glomerular neutrophil infiltrate was also reduced by these treatments; from
      42 +/- 3 to 25 +/- 1 in the case of anti-TNF-alpha and 47 +/- 2 to 30 +/- 1 with
      anti-IL-1 beta antibodies. In contrast, passive immunization against IL-1 alpha
      had no effect on either albumin excretion (4 +/- 3, 83 +/- 22 and 77 +/- 24 mg/24
      h), glomerular capillary thrombi (2 +/- 1; 19 +/- 5 and 16 +/- 3) or glomerular
      neutrophil infiltrate (22 +/- 3; 47 +/- 5 and 48 +/- 5 from the three groups
      respectively). These results demonstrate that enhanced antibody mediated injury
      in the kidney is modulated by TNF-alpha and IL-1 beta but not by IL-1 alpha.

PMID- 1385030
TI  - Description of a variably expressed and labile epitope of thyroglobulin and its
      occurrence in different thyroid diseases using a monoclonal antibody.
AB  - A new category of epitopes of human thyroglobulin is being described defined by a
      monoclonal antibody (TuTg 1). The epitope shows a very variable expression in
      normal individuals as well as in different thyroid diseases. According to gel
      filtration data the epitope is located at the intact molecule and is very
      sensitive to tryptic digestion. The monoclonal antibody was used in an IRMA
      system for plasma measurements in the follow-up of thyroid cancer patients. In
      individuals with high epitope expression the sensitivity to detect recurrency
      during T4 treatment was higher than a sensitive commercial TG IRMA.

PMID- 1385029
TI  - Neuronal ubiquitin and neurofilament expression in different lysosomal storage
      disorders.
AB  - We studied various lysosomal storage disorders such as Tay-Sachs' disease,
      Niemann-Pick's disease, and Hunter's disease for their immunoreactivity with
      antibodies against ubiquitin (Ub) and neurofilaments (NF). We found that in all
      cases, irrespective of the nature of the storage material or disorder, only a
      minor proportion of neurons (20-30% at most), as a rule, moderately reacted with
      the Ub antibody, while the majority of the distended neurons neither expressed Ub
      nor NF epitopes. These findings suggest that the UB dependent proteolytic pathway
      may play a secondary role in the lysosomal storage disorders, at least in the
      advanced stages which are observed at autopsy. It seems that the Ub expression of
      a minor proportion of neurons should be regarded as an unspecific epiphenomenon
      rather than as a mechanism of major significance in the basic metabolism of these
      disorders, in which the inclusions consist of membrane-bound lipid material.

PMID- 1385028
TI  - Analysis of lymphocyte phenotypes in cord blood from early gestation fetuses.
AB  - Using cord blood samples obtained from fetuses between 16 and 40 weeks gestation,
      we have used a lysed whole blood flow cytometric technique to study the natural
      history of lymphocyte phenotypes known to be highly represented in cord blood at
      birth. The majority (51.0 +/- 14.7%) of lymphocytes expressed CD45RA, a marker of
      'virgin' cells and there was a correlation between increasing percentages of
      CD45RA+lymphocytes and gestational age (r = 0.44, P < 0.01). Few cells (8.5 +/-
      4.2%) expressed the CD45RO marker of primed lymphocytes and very few (1.0 +/-
      0.7%) co-expressed CD45RA and RO, indicating little traffic between the two
      maturation markers. The percentage of B lymphocytes co-expressing CD5 was high in
      the fetal circulation (55.5 +/- 10.5%) compared with healthy adults (23.2 +/-
      14.3%; P < 0.00001) and the level of CD5+ B cells declined with gestational age
      in an exponential manner (r = -0.45, P < 0.05). Similarly, levels of T
      lymphocytes expressing the gamma delta T cell receptor (TCR) declined
      exponentially (r = -0.59, P < 0.005). These results demonstrate that lymphocytes
      remain almost entirely unprimed before birth. In addition, CD5+ B lymphocytes and
      TCR-gamma delta+ T lymphocytes decline exponentially towards birth, in a manner
      suggesting that they may be seeding peripheral sites such as the spleen, skin and
      mucosae.

PMID- 1385031
TI  - Generation of angiotensin II from human plasma by tissue kallikrein.
AB  - 1. Human plasma was incubated with tissue kallikrein from porcine pancreas,
      dialysed to obtain a fraction with a molecular mass < 10 kDa and further purified
      by reverse-phase chromatography. 2. Vasopressor activity in the fractions
      obtained was tested in the isolated perfused rat kidney. 3. In one fraction a
      strong vasopressor action was found, which was blocked by saralasin and by an
      angiotensin II antibody. 4. Aprotinin inhibited the formation of vasopressor
      substances by tissue kallikrein. 5. U.v.-laser desorption/ionization mass
      spectrometry revealed a molecular mass of 1046 Da in the purified active
      fraction. 6. It is concluded that tissue kallikrein forms not only kinins, but
      also angiotensin II, from human plasma under physiological conditions.

PMID- 1385032
TI  - [HIV infection and acquired immunodeficiency syndrome. III].
AB  - The present third note describes diagnostic procedures, prognosis, prophylaxis,
      therapy, and forensic medical problems connected with HIV infection and acquired
      immunodeficiency syndrome (AIDS). All these are topics of the utmost public
      health importance which have elicited much interest both among scientists and the
      general public also during the recent international conference held in Florence
      last June. HIV infection and the associated syndromes are extremely worrying in
      view of their increasing diffusion and extreme severity. In spite of the wealth
      of data already available, as yet we know little about this infection. Besides,
      all attempts at treatment and organization of prevention have proved ineffective,
      the latter being rendered vain by the extreme geographic spread of the disease,
      especially in underdeveloped countries where economic resources and individual
      and collective public health education are lacking. The fact of having
      successfully informed the medical profession about these complex problems, even
      though within the limits of the readers of this journal, is a source of
      satisfaction to us.

PMID- 1385033
TI  - Stimulation of actin and myosin synthesis in rat gastrocnemius muscle by
      clenbuterol; evidence for translational control.
AB  - 1. A transient rise in fractional rates of protein and actomyosin synthesis was
      observed in gastrocnemius muscles of rats fed clenbuterol for 1-2 days but the
      muscle RNA:protein ratio was unchanged, therefore protein synthesis per unit RNA
      (kRNA) also increased. 2. Myosin heavy and light chains and actin showed
      increased incorporation of [3H]phenylalanine at 2 days; these changes were
      proportional to increases in total protein synthesis. 3. The ratios actin
      mRNA:18S RNA and fast myosin heavy chain mRNA:18S RNA were unaffected by
      clenbuterol. 4. The data suggest that the clenbuterol-induced increase in muscle
      protein synthesis involves both translational control and increased tissue RNA.

PMID- 1385034
TI  - Effect of an antithyroid agent (propylthiouracil) and L-ascorbic acid on mixed
      function oxidase and drug metabolism in hepatic microsomes of chickens.
AB  - 1. The experiments were undertaken to determine if an antithyroid agent
      (propylthiouracil, PTU) and/or ascorbic acid (AA) affect mixed-function oxidase
      (MFO) in hepatic microsomes of male broiler chicks. 2. Feeding PTU increased the
      MFO activity in a dose-related manner. Addition of AA to the PTU-containing diet
      further increased the content of cytochromes P-450 and b5, but not the activities
      of NADPH-cytochrome c and NADH-cytochrome b5 reductase, and the drug-metabolizing
      enzymes. 3. Supplemental AA induced cytochrome b5 rather than cytochrome P-450.

PMID- 1385035
TI  - Quinacrine-staining of neurones, and activity of purine nucleosides and
      nucleotides in marine and terrestrial invertebrates from several phyla.
AB  - 1. The acridine derivative quinacrine was used to stain nerve fibres in internal
      organs of 17 species of marine and terrestrial invertebrates from seven different
      phyla. 2. The majority of preparations showed quinacrine-stained nerve fibres.
      There was a degree of variation, ranging from a dense network of nerve bundles to
      single fibres. Quinacrine-positive nerve cell bodies were also observed in some
      ganglia. 3. Pharmacological experiments were performed on a variety of isolated
      tissues from the different marine and terrestrial groups, in order to ascertain
      their sensitivity to adenine nucleosides and nucleotides. 4. Correlation is drawn
      between the ability of neurones within a tissue to bind quinacrine, and the
      ability of that tissue to respond to applied adenine nucleosides and nucleotides.

PMID- 1385037
TI  - Tumor fixation of bleomycin labeled with 57 cobalt before and after cryotherapy
      of bronchial carcinoma.
AB  - The combined effect of cryotherapy and chemotherapy was studied in 12 patients
      with bronchial carcinoma. Radiolabeled (57 Co) Bleomycin (BLM) was injected
      intravenously and initial detection was carried out with a gamma-camera. Plasma
      half-life and clearance of 57 Co-BLM, as well as tumor/normal tissues ratios were
      calculated. The same protocol was performed 15 days later immediately after
      cryotherapy. A mean increase of 30% of radiolabeled BLM was found in the tumor
      area after cryotherapy, and pharmacokinetic data were significantly different
      after cryotherapy. The vascular component of cryodestruction offers an
      explanation for these results, with trapping of the anticancer drug in the tumor
      and immediately surrounding area due to vascular stasis. It seems that
      chemotherapy may be more effective after cryotherapy, and a multicenter study is
      in progress to evaluate the association of cryo-chemotherapy in France.

PMID- 1385036
TI  - Congestive heart failure: survival trial of antiarrhythmic therapy (CHF STAT).
      The CHF STAT Investigators.
AB  - This study is a prospective, double-masked, randomized, clinical trial to
      determine the effect of anti-arrhythmic drug therapy on mortality in patients
      with congestive heart failure and ventricular arrhythmia. Patients will be
      assigned to receive either amiodarone or placebo. Eligible patients include those
      with ischemic and nonischemic congestive heart failure (New York Heart
      Association class III or VI) and with 10 or more ventricular premature beats per
      hour. All patients must have shortness of breath with minimal exertion or
      paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by
      echocardiogram of 55 mm or greater (> or = 55 mm) or a CT ratio of greater than
      0.5, and an ejection fraction of 40% of less. Patients will be entered into the
      study for 2.5 years and followed for an additional 2 years. Drug therapy will be
      continued for all patients throughout the entire study unless adverse reactions
      occur that necessitate individualized treatment. The expectation is that 674
      patients are to be entered into the study from 25 participating centers. This
      sample size will allow for the detection of a 33% decrease in 2-year mortality
      (20% vs. 30%) in the treated patients as compared to those in the placebo group
      with a power of 0.90 and a two-sided alpha level of 0.05. Intermittent Holter
      monitoring, radionuclide ventriculograms, pulmonary function tests,
      echocardiograms, and blood tests, including arterial blood gases, will be
      required for each patient. The study analysis will address differences in total
      mortality, cardiac mortality, and sudden cardiac death between patients receiving
      anti-arrhythmic drug therapy and those receiving placebo. Other factors to be
      examined include the effects of antiarrhythmic therapy on suppression of
      arrhythmias, on ejection fraction, and relation of ischemic events to mortality.

PMID- 1385038
TI  - Factors modulating the effect of retinoids on cultured retinal pigment epithelial
      cell proliferation.
AB  - The effect of several naturally-occurring retinoids and 13-cis-retinoic acid on
      the proliferation of cultured bovine retinal pigment epithelial (RPE) cells was
      investigated. None of the retinoids tested were toxic to the cultures and all,
      except retinylpalmitate, inhibited cell proliferation when given for more than 3
      days. The relative potencies of the retinoids were; all-trans-retinoic acid
      greater than 13-cis-retinoic acid greater than all-trans-retinol approximately
      equal to all-trans-retinaldehyde. Uptake of retinoic acid by cultured RPE cells
      was 10-fold less than the uptake of retinol. Although retinoic acid-treated
      cultures showed strong density-dependent growth inhibition, cellular
      proliferation was inhibited more in sparse cultures than in dense ones. Retinoic
      acid did not significantly inhibit the proliferation of first passage bovine or
      rabbit RPE cells, but partially inhibited the proliferation of first passage
      human RPE cells. The sensitivity of all these cultures to growth inhibition by
      retinoic acid increased in subsequent subcultures, yet there was no effect of
      passage number on retinoic acid uptake. This study demonstrates that RPE cell
      proliferation can be inhibited by retinoic acid but the sensitivity of these
      cells to the retinoid's effects are modulated by incubation time, in vitro aging,
      and cell density.

PMID- 1385039
TI  - Expression of K12 keratin in alkali-burned rabbit corneas.
AB  - The healing of alkali-injured corneas is characterized by the persistence of
      polymorphonuclear leukocytes (PMN) in tissues and recurrent corneal epithelial
      defects. It has been suggested that the proteolytic enzymes secreted by PMN may
      account in part for the recurrent epithelial defects in the alkali-burned
      corneas. Cytoplasmic keratins, which form intracellular intermediate filaments,
      participate in the formation of hemidesmosomes and play a key role in the focal
      adhesion of epithelial cells to the basement membranes. The K3/K12 keratin pair
      is a major constituent of differentiated and stratified corneal epithelium. We
      have recently cloned the cDNA encoding the rabbit K12 keratin. In the present
      study we examined the expression of K12 keratin during the healing of alkali
      burned rabbit corneas by slot-blot and in situ hybridization. Our results
      indicate that in normal cornea K12 keratin is equally expressed in all cell
      layers of stratified corneal epithelium and suprabasal layers of limbal
      epithelium, but not in bulbar conjunctival and other epithelia, i.e., lens, iris,
      and retinal pigment epithelium. The basal cells of the detached regenerating
      epithelium of the injured cornea express a very low level of K12 keratin. These
      observations are consistent with the notion that defective expression of K3/K12
      keratins may play a role in the abnormal attachment of the regenerating
      epithelium to the basement membrane.

PMID- 1385040
TI  - Rabbits have a circadian rhythm of aqueous humor cyclic AMP.
AB  - Rabbits have circadian rhythms of intraocular pressure (IOP) and aqueous flow.
      The dark phase increases of IOP and flow are associated with increased aqueous
      cyclic AMP. If the daily rhythm of aqueous cyclic AMP reflects changes of tissue
      levels of cyclic AMP which mediate one of the mechanisms which control the
      rhythms of IOP and aqueous flow, then it must be a circadian rhythm as are the
      rhythms of IOP and flow. A recent report showed no change in aqueous cyclic AMP
      from 2 hrs before to 2 hrs after the beginning of subjective dark in animals
      housed in constant dark. Because the increase of intraocular pressure at the same
      times did persist in constant dark, the authors concluded that a significant
      portion of the circadian rhythm of IOP is unrelated to cyclic AMP mediated ocular
      mechanisms. However, if an inhibitor of cyclic nucleotide phosphodiesterase is
      added to aqueous samples after harvesting by paracentesis, it is possible to show
      that most of the increase of aqueous cyclic AMP from mid-light phase to mid-dark
      phase persists in constant dark and is therefore likely to reflect a circadian
      rhythm of tissue cyclic AMP.

PMID- 1385041
TI  - Humoral immune response against the S-antigen/TNF alpha common epitope in rat EAU
      suppressed by the monoclonal antibody S2D2.
AB  - S-antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU) in rats can
      be suppressed by injecting the mouse monoclonal antibody (mAb) S2D2 or a
      polyclonal rat anti-idiotype S2D2 (anti-Id S2D2) antibody, the internal image of
      the epitope of S-Ag recognized by mAb S2D2. This epitope located in amino acids
      40-50 of bovine S-Ag (peptide S2), displays an homology with a sequence of human
      tumor necrosis factor alpha (hTNF alpha) (peptide RRAN) which is also recognized
      by S2D2. (Stiemer et al., this symposium). We show that one injection of S2D2 at
      the time of immunization with S-Ag suppressed EAU and modulated the production of
      antibodies against peptides of bovine or human S-Ag containing the S2 epitope and
      against peptide RRAN. Immunization against anti-Id S2D2 stimulated antibody
      production to peptide S2 and RRAN and inhibited EAU. These data suggest that
      disease suppression could be related to the production of antibodies against the
      S-Ag/TNF alpha common epitope.

PMID- 1385042
TI  - Molecular aspects of autoimmunity: a review.
AB  - Molecular genetic techniques are being widely applied to the study of autoimmune
      diseases. Major advances have been made in diabetes, rheumatoid arthritis and
      coeliac disease. Work on experimental models of autoimmune uveitis suggests that
      similar advances will follow in this field. The application of molecular genetics
      to the study of immunology has lead to great advances in our understanding of the
      anatomy of antigen recognition. This work has lead to the identification of some
      of the structural determinants of antigen binding by MHC molecules and is helping
      to explain some MHC-disease associations. More recently, molecular studies of the
      T cell receptor have characterized patterns of T cell receptor expression in
      humans and have lead to the identification of regions of the T cell receptor
      critical for antigen recognition. These techniques will hopefully provide
      insights into the nature of autoimmunity and permit the identification of targets
      for disease specific immunotherapies. This review describes attempts to corelate
      MHC structure and function in the context of autoimmunity and discusses some of
      the strategies for analyzing T cell receptor usage in autoimmune disease.

PMID- 1385043
TI  - Cytokine induction by immunomodulatory epitopes in S-antigen and tumor necrosis
      factor alpha.
AB  - Common epitopes on S-antigen (arrestin), a potent autoantigen inducing
      experimental autoimmune uveoretinitis (EAU), and on human tumor necrosis factor
      alpha (hTNF alpha) are revealed with monoclonal antibodies (mAb) to S-antigen,
      which inhibit EAU induction. The minimal common sequence for mAb recognition is
      GVxLxD in the S-antigen/hTNF alpha amino acid (aa) sequences. Peptides containing
      this sequence motif exhibit monocyte activating capacity analogous to the
      autocrine stimulatory capacity of hTNF alpha itself. In S-antigen this activity
      is located at epitope S2 (aa residues 40 to 50), corresponding to the peptide
      PVDGVVLVDPE (peptide S2). In hTNF alpha the monocyte activating capacity
      correlates to aa residue 31 to 53, corresponding to the peptide
      RRANALLANGVELRDNQLVVPSE (peptide RRAN). Peptide S2 but not peptide RRAN is
      competing for mAbs S6H8 and S2D2 binding to S-antigen. Anti-idiotypic antibodies
      to S2D2 compete with peptide S2 but not peptide RRAN for binding to mAbs S2D2 and
      S6H8. In human retinal S-antigen epitope S2 is localized at the aa residues 44-54
      and is cleaved in the human peptide 4 (aa 31-50). Competition experiments with
      peptide 4 (aa 31-50) and peptide 5 (aa 41-60) indicate that the C-terminal aa
      residues VDPD in the epitope S2 play an important role for internal image
      recognition of the anti-idiotypic antibodies. Peptide S2 and peptide RRAN define
      common functional structures in the autoantigen and hTNF alpha molecules. The
      data suggest regulatory functions of the peptides in cytokine expression, network
      regulation and in autoimmunity.

PMID- 1385044
TI  - Unresponsiveness to self-peptides of S-antigen in EAU: an overview of recent
      results.
AB  - Several observations in the characterization of EAU are examined. First,
      sequences of heterologous S-Ag (bovine S-Ag in LEW rats) which induce strong in
      vitro T cell proliferative responses are dissociated from sequences which induce
      EAU. Strong in vitro responses were detected only to nonself peptide homologues.
      Second, T cells specific for self-sequences of S-Ag are unresponsive in vitro.
      Third, TCR V beta 8 gene usage is associated with pathogenic T cells. V beta 8.2
      bearing hybridomas from a pathogenic line exhibited enhanced reactivity to
      pathogenic self-peptides, but were unresponsive unless presented Ag on
      nonirradiated, splenic APC. We propose that these findings reflect self, nonself
      discrimination of the epitopes on heterologous autoantigen, and examine the
      hypothesis that TCR containing V beta 8 have enhanced avidity for MHC complexed
      with autologous sequences, but that these V beta 8 autoreactive T cells appear
      unresponsive in vitro due to mechanisms of self-tolerance involving
      superantigen/coligand participation.

PMID- 1385045
TI  - Preclinical and clinical study of FK506 in uveitis.
AB  - Efficacy of a new immunosuppressive agent, FK506, in refractory uveitis was
      studied in 8 patients: 5 with Behcet's disease and 3 with idiopathic retinal
      vasculitis. The agent was given by oral administration every 12 hours. The
      previous therapy with systemic corticosteroids or immunosuppressive agents
      including cyclosporine failed to subside uveitis in these cases. During the
      observation period of 21.6 +/- 7.8 weeks (mean +/- SD) under FK506 at doses with
      0.05, 0.1, 0.15 or 0.2 mg/kg/day, the visual acuity was increased in 44% of
      treated eyes, unchanged in 44% and decreased in 12%. The inflammatory activity in
      the ocular fundus was improved in 69% and unchanged in 6% of treated eyes. The
      effects of FK506 on uveitis by the criteria of improvement of visual acuity and
      uveitis activity was dose-dependent: 0.05 and 0.1 mg/kg/day were ineffective but
      0.15 and 0.2 mg/kg/day were effective in most cases. One patient with Behcet's
      disease converted from cyclosporine developed moderate renal impairment in 4
      weeks under FK506 and the therapy was discontinued in 8 weeks, though the uveitis
      activity as well as visual acuity was markedly improved. Other 7 cases had no
      side effect of FK506. Although the number of cases was small and observation
      period was short, the present clinical data indicate that FK506 is effective to
      treat refractory uveitis.

PMID- 1385046
TI  - Membrane inhibitor of reactive lysis.

PMID- 1385047
TI  - Decay accelerating factor (CD55).

PMID- 1385048
TI  - Lipopolysaccharide receptors and signal transduction pathways in mononuclear
      phagocytes.
AB  - There is little question but that bacterial lipopolysaccharides (LPS) remain one
      of the most potent stimuli which can affect macrophage activation. Although the
      precise biochemical mechanisms responsible for this remain to be fully defined,
      there is now evidence accumulating from a number of laboratories that functional
      receptors for these bacterial products do exist and may contribute to the initial
      triggering event. Unfortunately, there is currently no consensus as to which of
      the candidate receptors identified to date serves as the primary binding target
      for LPS, and it is possible that the difference in macrophage cell types, LPS
      probes, and detection systems will all influence the nature of the binding. At
      the present time, therefore, macromolecules of 96-kDa, 95-kDa (adhesion beta
      chain), 80-kDa, 65-kDa, and 55-kDa may be considered as possible LPS targets.
      With the exception of the 96-kDa protein identified by Hampton and his co
      workers, there exists some experimental evidence for a functional role for each
      of the molecules so far identified. It is apparent that the molecular cloning and
      sequencing and subsequent biochemical characterization of these LPS receptors
      will be required to determine unequivocally their role in LPS-mediated triggering
      events. Such information will be invaluable in sorting out the relevant
      biochemical second signals involved in macrophage activation. Although much new
      information has recently been accumulated on potential signaling pathways for
      LPS, the definitive events remain far from unequivocally established. In view of
      the obvious importance of LPS-macrophage interactions in the overall capacity of
      the mammalian host to respond appropriately to the potentially hostile
      prokaryotic environment, a precise delineation of LPS-mediated macrophage
      activation is critical to our understanding of this important inflammatory
      mediator cell.

PMID- 1385049
TI  - Localization of the cystic fibrosis transmembrane conductance regulator (Cftr) to
      mouse chromosome 6.

PMID- 1385050
TI  - Late-effects after treatment for germ-cell cancer with cisplatin, vinblastine,
      and bleomycin.
AB  - During a 5-year period from 1979 to 1983 all patients in Denmark with metastatic
      non-seminomatous and extragonadal germ cell cancer were treated with 6 cycles of
      cisplatin, vinblastine, and bleomycin (PVB). Thirty-nine patients referred to the
      Finsen Institute accepted a follow-up examination of side-effects 3.5-9 years
      after chemotherapy. Renal toxicity consisted of an irreversible decrease in
      glomerular filtration rate (GFR) in 47% of the patients, while the decrease in
      GFR was fully reversible in 23%. Significant pulmonary toxicity was observed in
      smokers and consisted of an irreversible decrease in carbon monoxide diffusion
      capacity to median 72% of the predicted value. Neurotoxicity was the most
      pronounced long-term side-effect. Nearly all patients had a peripheral sensory
      neuropathy probably caused by axonal degeneration. A central conduction defect
      was observed in 88% of the patients by measuring auditory brain-stem potentials.
      Irreversible high-frequency hearing loss was induced in 39% of the patients.
      Parasympathetic nerve dysfunction was found in 36% of the examined patients,
      including 2 patients with impotence. Half of the patients revealed Raynaud's
      phenomenon (RP), and the mechanism underlying this side-effect was found to be
      hyperreactivity of the central sympathetic nervous system. Vascular toxicity was
      found only in terminal arterioles and was not responsible for RP. PVB treatment
      caused low sperm counts and a subclinical Leydig cell dysfunction in the majority
      of patients. Azoospermia was observed in 27% of the patients. Six patients had
      hypertension and this was not related to renal impairment.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1385051
TI  - A prospective study of amylase-rich pleural effusions with special reference to
      amylase isoenzyme analysis.
AB  - By analysis of pleural effusions from 200 patients, 25 cases of amylase-rich
      effusions were identified, for an overall incidence of 13 percent. Four of the 25
      patients (16 percent) had evidence of pancreatitis. These patients had higher
      mean ratios of pleural fluid to serum amylase levels (18 +/- 6.3 [SEM] vs 4.8 +/-
      1.3) compared to patients with nonpancreatic diseases (p = 0.003); all four
      exhibited a predominant pancreatic isoenzyme profile. Of the 21 patients with
      nonpancreatic amylase-rich effusions, lung cancer was the most commonly
      associated condition (8 patients). In 14 of the 21 patients in whom an isoenzyme
      profile was obtained, salivary-type amylase was predominant. Amylase-rich pleural
      effusions occur frequently, and pleural fluid isoamylase determination is
      specific for pancreatitis-associated effusions. The finding of a pleural effusion
      rich in salivary isoamylase should prompt an evaluation for carcinoma
      (particularly of lung primary), but may also be seen in other pleural
      inflammatory conditions.

PMID- 1385052
TI  - Proteinase/proteinase inhibitor imbalance in sputum sol phases from patients with
      chronic obstructive pulmonary disease. Suggestions for a key role played by
      antileukoprotease.
AB  - In order to characterize the imbalance between proteinases and proteinase
      inhibitors in sputum sol phases, we studied 25 patients (mean age, 59 +/- 11 yr)
      with exacerbated chronic obstructive pulmonary disease (COPD). An aliquot of
      sputum was used for bacteriologic determinations, and the remainder was
      centrifuged in order to obtain gel and sol phases. On the basis of the
      bacteriologic data, patients were divided into colonized patients (14) and
      noncolonized patients (11). All of the major inhibitors were immunologically
      detectable in sol phases without a significant difference between colonized and
      noncolonized patients (alpha 1-proteinase inhibitor [alpha 1-PI], 2.56 microM +/-
      0.53 microM and 2.39 microM +/- 0.72 microM; alpha 2-macroglobulin [alpha 2-MG],
      0.21 microM +/- 0.07 microM and 0.16 microM +/- 0.05 microM; antileukoprotease
      (ALP), 1.78 microM +/- 0.57 microM and 1.53 microM +/- 0.6 microM, respectively
      [mean +/- SE]). With regard to proteinase activities, both free elastase-like and
      free chymotrypsin-like activities were detectable in the majority of patients
      (15/25) (0.59 microM +/- 0.15 microM and 0.74 microM +/- 0.15 microM for elastase
      like activity [ELA], and 0.010 microM +/- 0.003 microM and 0.017 microM +/- 0.007
      microM for chymotrypsin-like activity [CLA], respectively [mean +/- SE]). The
      inhibitory profile of proteinase activities, performed by means of a panel of
      inhibitors, allowed us to assign specific activities mainly to neutrophil
      elastase and cathepsin G (Cat G). Next we looked at the relationships between
      inhibitors and proteinase activities. We found a significant negative correlation
      between neutrophil elastase activity and ALP (r = -0.58; p < 0.01). In
      confirmation of this suggestion, sol phases were divided into samples (15) with
      detectable ELA (> 0.50 microM) and samples (10) with no detectable ELA (< 0.18
      microM). Levels of alpha 1-PI and alpha 2-MG did not differ significantly between
      the two groups, whereas ALP values were higher in the group with no detectable
      ELA (3.12 microM +/- 0.69 microM) than in the other group (0.58 microM +/- 0.21
      microM; p < 0.001). We conclude that most sputum sol phases from patients with
      exacerbated COPD have a high burden of free neutrophil elastase and Cat G.
      Antileukoprotease seems to be the major naturally occurring inhibitor effective
      in the modulation of proteinase activities in bronchial secretions under these
      conditions.

PMID- 1385053
TI  - Hoechst 33258, distamycin A, and high mobility group protein I (HMG-I) compete
      for binding to mouse satellite DNA.
AB  - The experiments described were designed to test the hypothesis that the (A+T)
      specific DNA binding ligands Hoechst 33258 and distamycin A affect the
      condensation of mouse centromeric heterochromatin by competing for binding to
      satellite DNA with one or more chromosomal proteins. The studies focused on the
      nonhistone chromosomal protein HMG-I since its binding properties predict it
      would be a target for competition. Gel mobility shift assays show that HMG-I
      forms specific complexes with satellite DNA and that the formation of these
      complexes is competed for by both Hoechst and distamycin. In addition, methidium
      propyl EDTA Fe(II) [MPE Fe(II)] footprints of ligand-satellite DNA complexes
      showed essentially the same protection pattern for both drugs and a similar, but
      not identical, HMG-I footprint. If these in vitro results reflect the in vivo
      situation then the incomplete condensation of centromeric heterochromatin
      observed when mouse cells are grown in the presence of either chemical ligand
      could be a consequence of competition for binding of HMG-I (and possibly other
      proteins) to satellite DNA.

PMID- 1385055
TI  - Peptidergic neurotransmitters in the endocrine hypothalamus.
AB  - More than 20 neuropeptides have been localized in the endocrine hypothalamus.
      They may exert a neurohormonal effect on the pituitary or innervate other neurons
      (intranuclear, intrahypothalamic or extrahypothalamic) and act as
      neurotransmitters. Many of the hypothalamic neuropeptides are synthesized as
      inactive precursors that are activated by proteolysis during axonal transport
      from the cell body to the synapse. Studies in which the paraventricular nuclei
      were bilaterally destroyed have shown that the neuroendocrine cells in the
      hypothalamus show functional plasticity and cells that do not usually make
      detectable quantities of a particular neuropeptide may be activated to do so.
      Within the hypothalamic nuclei are dense networks of synaptic connections among
      neurons synthesizing the same or different neuropeptides. These local circuits
      may coordinate the activities of peptidergic neurons in a hypothalamic nucleus.
      Hypothalamic neurons project axons to the median eminence-pituitary stalk and the
      posterior pituitary, also to nuclei within the hypothalamus and to
      extrahypothalamic areas such as the lower brainstem. Peptidergic neurons in the
      hypothalamus can have combined neurohormonal and neurotransmitter activities
      mediated by axon terminals on portal capillaries and other hypothalamic nuclei.
      Double labelling immunohistochemistry has been used to demonstrate reciprocal
      connections between peptidergic neurons in the hypothalamus, such as those
      synthesizing growth hormone-releasing hormone and somatostatin.

PMID- 1385054
TI  - Regulation of expression of the interleukin 6 gene: structure and function of the
      transcription factor NF-IL6.
AB  - The interleukin 6 (IL-6) promoter is rapidly and transiently activated by other
      cytokines, including IL-1 and tumour necrosis factor (TNF), as well as by phorbol
      esters and cyclic AMP agonists. Studies using promoter mutants suggested that an
      IL-1-responsive element mapped within the -180 to -123 region of the IL-6
      promoter. A nuclear factor (NF-IL6) that recognized a unique sequence containing
      an inverted repeat, ACATTGCACAATCT, was identified within the region. Direct
      cloning of the human NF-IL6 revealed its similarity to C/EBP, a liver- and
      adipose tissue-specific transcription factor. C/EBP and NF-IL6 recognize the same
      nucleotide sequence, but exhibit distinct patterns of expression. NF-IL6 is
      expressed at a low level in normal tissues, but is rapidly and drastically
      induced by bacterial lipopolysaccharide (LPS) or inflammatory cytokines such as
      IL-1, TNF and IL-6. Recently, NF-IL6 has been shown to be identical to IL-6DBP,
      the DNA-binding protein which is responsible for IL-6-mediated induction of
      several acute-phase proteins. Evidence that NF-IL6 DNA-binding activity is
      increased after IL-6 stimulation without increased NF-IL6 protein synthesis
      demonstrates the importance of post-translational modification. There are some
      results indicating that phosphorylation is involved in transcriptional and
      binding activities of NF-IL6. Taken together, these findings indicate that NF-IL6
      may be an important transcription factor on the signal transduction pathways of
      IL-1 and IL-6.

PMID- 1385056
TI  - Determination of tumor marker levels in cystic fluid of benign liver cysts.
AB  - The levels of tumor markers in cystic fluid and serum were measured in six
      patients with benign biliary cyst of the liver. AFP in the cystic fluid was lower
      than the upper normal limit for serum in all cases, and CEA in the cystic fluid
      was higher than the upper normal limit for serum in one of the six cases. CA19-9,
      DU-PAN 2, and SPAN 1 in cystic fluid were much higher than the upper normal limit
      for serum in all cases (more than 100-fold for CA19-9, twofold for DU-PAN 2, and
      ninefold for SPAN 1). CA19-9, DU-PAN 2, and SPAN 1 in cystic fluid were
      significantly higher than the levels in the corresponding serum. Positive
      immunohistochemical staining against CA19-9, DU-PAN 2, and SPAN 1 was observed in
      the cytoplasm of the epithelial cells of the cyst wall. These results suggested
      that the high concentrations of CA19-9, DU-PAN 2, and SPAN 1 in the cystic fluid
      were due to secretion from the epithelial cells in the benign biliary cysts.

PMID- 1385058
TI  - Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and
      rapamycin in man and rat.
AB  - The hepatic cytochrome P-450 responsible for metabolism of the structurally
      related macrolides FK506 and rapamycin in humans was identified using in vitro
      studies. FK506 and rapamycin metabolism was significantly correlated with
      nifedipine oxidation in human liver microsomes of eight different individuals.
      Immunoinhibition with anti-P450 3A4 abolished almost all FK506 and rapamycin
      metabolite formation. Inactivation of P450 3A4 by incubation of human liver
      microsomes with triacetyl oleandomycin (50 microM) or gestodene (10 microM)
      inhibited metabolism of FK506 and rapamycin. In liver microsomes from
      dexamethasone-treated rats FK506 and rapamycin metabolism was increased compared
      to liver microsomes from uninduced, phenobarbital-, or 3-methylcholanthrene
      induced rats. FK506 and rapamycin were metabolized by reconstituted recombinant
      human liver P450 3A4. It is concluded that in human and rat liver FK506 and
      rapamycin are metabolized primarily by cytochrome P-450 3A4.

PMID- 1385059
TI  - [Hazards in the surgical field].

PMID- 1385057
TI  - Substance P, vasoactive intestinal polypeptide, and gastrin catabolism in canine
      liver and kidney.
AB  - No reports have described the catabolic mechanism of substance P in vivo. We
      studied the effects of hepatic or renal transit on substance P, vasoactive
      intestinal polypeptide, and gastrin in anesthetized dogs. It was found that the
      liver plays a more important role in vasoactive intestinal polypeptide catabolism
      than the kidney and that the kidney is more important in gastrin catabolism than
      the liver. Substance P was more rapidly degraded than the other two peptides in
      both organs. The transrenal substance P loss measured by C-terminal antiserum
      differed from that measured by N-terminal antiserum, although there was no
      difference in the liver. This suggested that there were different patterns of
      cleavage of substance P between the liver and the kidney, and that its C terminal
      was degraded more strongly than its N terminal in the kidney.

PMID- 1385060
TI  - [Metal endoprostheses for endoscopic therapy in malignant bronchial tumors].
AB  - Self-expanding metal stents were implanted in the trachea or main bronchus in 12
      patients (eleven men, one woman; mean age 60 +/- 8 years) with nonresectable
      bronchial carcinoma (n = 11) or tracheal metastasis of a hypernephroma (n = 1).
      They all had pulmonary complications caused by tumour stenoses (group I: severe
      dyspnoea [n = 6], group II: retention pneumonia [n = 4] or lung abscess [n = 2]
      after unsuccessful antibiotic treatment). The procedure was undertaken after
      local anaesthesia with a flexible bronchoscope (in the first three cases still
      with a rigid bronchoscope under general anaesthesia) under fluoroscopic control.
      Immediate reduction in dyspnoea occurred in five of the six patients in group I.
      In five of the six patients in group II antibiotics cured the infection after
      stent placement. The therapeutic effect was immediate in severe dyspnoea and
      retention of secretions. The clinical improvement lasted longer in patients with
      abscess and retention pneumonia than those with dyspnoea (41 +/- 16 vs. 26 +/- 10
      days). If strict indications are observed in cases with malignant bronchial
      stenosis, implantation of self-expanding stents provides rapidly effective, well
      tolerated palliation.

PMID- 1385061
TI  - [The content of DNA, RNA and wet weight and the RNA:DNA and wet weight:DNA ratio
      in different tissues during the growth of chickens. 1. Analysis of the brain, the
      myocardium, the lungs and the liver].
AB  - At each 8 chickens of the race "white leghorn" analyses of the body weight as
      well of the wet weight and the concentration of DNA and of RNA in different
      tissues from the 2nd to the 203rd day after hatching were performed. On the 2nd
      day after hatching the DNA-concentration in the brain amounted to 1.50 +/- 0.12,
      in the heart-muscle to 2.86 +/- 0.19, in the lung to 7.23 +/- 0.19 and in the
      liver to 2.86 +/- 0.20 mg/g wet weight. The highest content of nuclei in the
      brain of 1.38 x 10(9) was estimated on the 56th, in the heart-muscle of 1.94 x
      10(9) on the 168th day, in the lung of 16.86 x 10(9) on the 112th day and in the
      liver of 69.81 x 10(9) on the 203rd day. Further the RNA:DNA- and the wet
      weight:DNA-ratio of the different tissues was calculated.

PMID- 1385062
TI  - Differential expression of acidic cytokeratins 18 and 19 during sexual
      differentiation of the rat gonad.
AB  - The expression of cytokeratins (CKs) 8, 18 and 19 was analyzed in male and female
      rat gonads from the undifferentiated stage (12.5 days of gestation) until two
      weeks after birth by indirect immunofluorescence, using specific monoclonal
      antibodies anti-CK 8 (LE41), anti-CK 19 (LP2K) and anti-CK 18 (LE65 and RGE53).
      In the undifferentiated blastema, the somatic cells were stained for CK 8 and CK
      19, whereas no detectable immunoreactivity for CK 18 was obtained. The same
      staining CK pattern was observed in ovaries, in the somatic cells of ovigerous
      cords and in primary follicles. The staining was progressively decreasing in
      growing follicles after one week after birth. At the onset of testicular
      differentiation, when the first Sertoli cells differentiate in the gonad of 13.5
      day old male fetuses, positive staining for CK 18 became evident, in addition to
      CK 8 and CK 19 expression. In the following days, CK 8, CK 18 and CK 19 were
      detected in Sertoli cells in the differentiating seminiferous cords, but
      progressively the reactivity for CK 19 decreased and was no longer observed after
      18.5-19.5 days of gestation. In all cases, CKs were found to be coexpressed with
      vimentin, and germ cells were negative for both vimentin and CKs. The results
      reported here show first, that CKs are expressed before sexual differentiation in
      gonadal blastema in which no epithelial organization is observed, and second,
      that there is a CK 18/CK 19 shift in expression during morphogenesis of the
      testis which is not observed in the differentiating ovary. Future studies will
      have to determine whether these differences in CK expression are due to epitope
      masking phenomena or to the regulation of CK synthesis.

PMID- 1385063
TI  - Characterization of HNK-1 antigens during the formation of the avian enteric
      nervous system.
AB  - During vertebrate embryogenesis, interaction between neural crest cells and the
      enteric mesenchyme gives rise to the development of the enteric nervous system.
      In birds, monoclonal antibody HNK-1 is a marker for neural crest cells from the
      entire rostrocaudal axis. In this study, we aimed to characterize the HNK-1
      carrying cells and antigen(s) during the formation of the enteric nervous system
      in the hindgut. Immunohistological findings showed that HNK-1-positive
      mesenchymal cells are present in the gut prior to neural crest cell colonization.
      After neural crest cell colonization this cell type cannot be visualized anymore
      with the HNK-1 antibody. We characterized the HNK-1 antigens that are present
      before and after neural crest cell colonization of the hindgut. Immunoblot
      analysis of plasma membranes from embryonic hindgut revealed a wide array of HNK
      1-carrying glycoproteins. We found that two HNK-1 antigens are present in E4
      hindgut prior to neural crest cell colonization and that the expression of these
      antigens disappears after neural crest colonization. These two membrane
      glycoproteins, G-42 and G-44, have relative molecular masses of 42,000 and
      44,000, respectively, and they both have isoelectric points of 5.5 under reducing
      conditions. We suggest that these HNK-1 antigens and the HNK-1-positive
      mesenchymal cells have some role in the formation of the enteric nervous system.

PMID- 1385064
TI  - Beta 1-integrin is a maternal protein that is inserted into all newly formed
      plasma membranes during early Xenopus embryogenesis.
AB  - A monoclonal antibody (mAb 8C8) that recognizes the Xenopus beta 1-integrin chain
      was used to study the appearance, synthesis and distribution of this integrin
      subunit during the early development of Xenopus. Both the precursor and the
      mature form of beta 1-integrin are provided maternally. They do not increase
      significantly in amount until early gastrula when the level of both forms begins
      to rise gradually. Synthesis of beta 1-integrin from maternal mRNA is observed
      throughout the pregastrula phase, though it seems to add only little to the total
      beta 1-integrin of the embryo. Until late blastula only small amounts of
      precursor are processed into the mature form. Starting with the formation of the
      first cleavage membrane, mature beta 1-integrin is inserted into the newly formed
      plasma membranes of all cells. The membrane domains forming the outer surface of
      the embryo remain devoid of the antigen. The data suggest an as yet unknown
      function of beta 1-integrin during the cleavage phase.

PMID- 1385065
TI  - IGF binding protein-2 gene expression and the location of IGF-I and IGF-II in
      fetal rat lung.
AB  - Binding proteins for the insulin-like growth factors (IGF-BPs) are important
      modulators of the biological actions of IGF-I and IGF-II. The generation of
      IGFBPs within developing organs, and their spatial arrangement, may similarly
      determine IGF action at specific microanatomical sites. In situ hybridization
      studies with late gestation (days 16, 18 and 20) fetal rat lung using a cDNA
      probe for IGFBP-2 showed strong gene expression in the fetal lung epithelial
      structures (alveoli and airways). The sites of IGFBP-2 gene expression were
      associated with immunoreactive IGF-II at the apical surface of the epithelium. By
      day 20, there was also some IGFBP-2 gene expression and immunoreactive IGF-II at
      discrete sites in the mesenchyme. In contrast, immunoreactive IGF-I was found
      predominantly distributed in a punctate pattern, consistent with its presence in
      the lumen or walls of small vessels or capillaries, and in a granular,
      intracellular form in both epithelial and mesenchymal cells. These studies
      suggest that endogenously generated IGFBP-2 may determine the distribution of IGF
      II, principally at the apical surface of lung epithelia. IGF-I does not
      colocalise with IGF-II peptide or the sites of IGFBP-2 gene expression. We
      conclude that the spatial distributions of these two related growth factors are
      separately controlled, to some extent by endogenously generated binding proteins.

PMID- 1385066
TI  - Mechanisms and consequences of portal hypertension.
AB  - Portal hypertension is characterised by alterations in the splanchnic and
      systemic circulation resulting in the development of portosystemic collateral
      channels, the most important of which are found in the lower oesophagus and
      stomach. The major clinical complication of gastro-oesophageal varices is
      bleeding and over the last decade there has been considerable interest in the
      pharmacological management of this complication. The factors currently implicated
      in the development of gastro-oesophageal varices in patients with cirrhosis
      include a) increased portal vascular resistance, b) splanchnic and systemic
      vasodilatation and c) changes in the lower oesophageal venous anatomy [palisade
      and perforating venous zones]. In a patient with gastrointestinal bleeding,
      endoscopic examination of the upper gastrointestinal tract will confirm the
      diagnosis of portal hypertension by confirming the presence of gastro-oesophageal
      varices. Cirrhosis is the most common aetiological factor for gastro-oesophageal
      varices, but imaging techniques, including Doppler ultrasound, computerised
      tomography and venous phase angiography, may be required to exclude extrahepatic
      portal venous obstruction from the differential diagnosis. Although the
      pathogenesis of variceal rupture remains unclear, several risk factors for
      variceal haemorrhage have been identified, including a) increased size, b) high
      intravariceal-portal pressure, c) increased varix wall tension characterised by
      the presence of red spots observed at endoscopy (particularly in large varices
      since wall tension is related to variceal size), and d) poor liver function.
      Although oesophagitis may be observed at endoscopy, an erosive mechanism is no
      longer considered to be of pathogenic significance. A high portal pressure in the
      immediate postbleeding period is now recognised as predictive of rebleeding.
      Periodic elevations in intravariceal pressure, associated with the release of
      enhanced endogenous vasoactive compounds, or beta-adrenergic-mediated stress
      related increases in portal pressure, may contribute to the rupture mechanism.
      Consequently, portal hypertension is now being more widely considered as a
      multiorgan disorder associated with changes in blood flow within both systemic
      and splanchnic vascular beds. This article reviews the factors currently
      implicated in the development of portal hypertension and the approach to
      diagnosis. The pathogenesis of variceal bleeding will also be considered.

PMID- 1385067
TI  - Acute management of bleeding oesophageal varices.
AB  - The goals of therapy in acute variceal bleeding are to arrest haemorrhage and to
      prevent deterioration of liver function and complications related to bleeding.
      The measures used to stop acute bleeding should, ideally, also prevent the very
      early rebleeding that is frequently seen with bleeding varices. Variceal bleeding
      should be managed by a gastrointestinal bleeding team with intensive nursing
      care. Diagnostic endoscopy is mandatory once initial resuscitation has been
      achieved, and allows immediate injection sclerotherapy of varices. Drug therapy
      can be used as the first treatment in patients admitted with variceal bleeding
      since it can be given immediately. Of the available drugs, somatostatin has the
      least side effects and is as effective as vasopressin, terlipressin and the
      combination of vasopressin and an organic nitrate vasodilator. The role of drugs
      needs to be studied in combination with sclerotherapy. Sclerotherapy remains the
      mainstay of management as it achieves the twin goals of stopping active bleeding
      and preventing early rebleeding. Injection of tissue adhesive and endoscopic
      ligation or 'banding' are new endoscopic techniques that have shown promise in
      preliminary trials and are currently being assessed more widely. Balloon
      tamponade is a temporary measure used to prevent exsanguination. Surgery should
      be reserved for those patients in whom sclerotherapy is unsuccessful or cannot be
      carried out. Oesophageal staple transection is the most used operation. The new
      interventional radiological technique of transjugular intrahepatic portosystemic
      shunting will probably replace surgery in the future, but its role in acute
      variceal bleeding has yet to be fully defined.

PMID- 1385068
TI  - Somatostatin in acute bleeding oesophageal varices. Pharmacology and rationale
      for use.
AB  - Somatostatin was originally isolated from the hypothalamus, but has subsequently
      been found throughout the whole gastrointestinal tract. It exerts an inhibitory
      effect upon numerous functions of the body, and, therefore, increasing attention
      has been focused on its potential as a therapeutic agent with cytoprotective
      properties and a potent inhibitory action on a wide variety of functions in
      endocrine diseases, cancer and gastrointestinal haemorrhage, including bleeding
      from oesophageal varices. As somatostatin has a very short plasma half-life and
      requires administration by continuous infusion to maintain therapeutic levels,
      stable long-acting analogues have been developed. The analogue octreotide has
      been shown to have a plasma half-life of 113 minutes and to produce a profound
      selective inhibition of growth hormone. Hepatic excretion of octreotide has been
      estimated to be between 30 and 40% in healthy volunteers; no data are available
      in cirrhotic patients. A review of published data assessing systemic and hepatic
      haemodynamics in animals and humans over varying dosage regimens of somatostatin
      and octreotide reveals that cardiac output, arterial pressure and peripheral
      resistance are modified more in animals than in humans. Hepatic haemodynamics are
      significantly altered in animals as well as in humans in most of the studies.
      Circumstantial evidence is provided indicating that the mechanisms of action of
      somatostatin and octreotide in the therapy of bleeding oesophageal varices are
      mainly mediated by a splanchnic vasoconstrictive effect. Furthermore, gastric
      acid suppression and potential enhancement of platelet aggregation may contribute
      to the beneficial outcome after treatment of oesophageal varices with
      somatostatin.

PMID- 1385069
TI  - Somatostatin in acute bleeding oesophageal varices. Clinical evidence.
AB  - Following the demonstration that somatostatin lowered portal pressure in
      cirrhotic patients with portal hypertension, 2 uncontrolled reports suggested
      that the hormone might be useful in the control of acute variceal haemorrhage.
      Subsequently, a number of randomised controlled trials have indicated that
      somatostatin may have an efficacy as good as or better than either vasopressin or
      combined vasopressin and nitroglycerin therapy and is associated with fewer side
      effects. Somatostatin has an efficacy comparable to balloon tamponade, histamine
      2-receptor antagonists and injection sclerotherapy. One double-blind randomised
      controlled trial demonstrated a significant benefit of somatostatin over placebo
      in the control of variceal bleeding whereas a second did not show any significant
      difference between treatments. In all the controlled trials, the average control
      rate achieved with somatostatin administration was 69% and it was not associated
      with any major side effects. Somatostatin administration has also been shown in
      uncontrolled series to be very effective in controlling postinjection
      sclerotherapy bleeding from the varices per se, and from oesophageal ulcers and
      oesophagitis. Few data are available on the long acting analogue of somatostatin,
      octreotide, but preliminary data suggest that it may be as effective and safe as
      the native hormone in controlling the acute variceal bleeding and postinjection
      sclerotherapy haemorrhage. It is concluded that there may be a case for
      instituting somatostatin therapy as soon as the patient enters hospital to
      facilitate sclerotherapy, and for continuing treatment for 5 days after
      sclerotherapy when the risk of recurrent bleeding is highest.

PMID- 1385071
TI  - Effects of benzo[a]pyrene on steady-state levels of biogenic amines and
      metabolizing enzymes in mouse brain regions.
AB  - Benzo[a]pyrene (BaP) is a product of incomplete fossil fuel combustion, a well
      known pollutant, and a carcinogenic agent. In the present study male CD-1 mice
      received ip injections of 0, 5, 25, and 100 mg/kg body weight BaP twice a week
      for 3 weeks. Endogenous levels of brain biogenic amines and their selected
      metabolites, norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT),
      vanillylmandelic acid, dihydroxyphenylacetic acid (DOPAC), homovanillic acid, and
      5-hydroxyindoleacetic acid (5-HIAA) were measured using high performance liquid
      chromatography and electrochemical detection. The brain regions studied were
      cortex, striatum, hypothalamus, midbrain, medulla oblongata, and cerebellum. BaP
      treatment increased the steady-state levels of NE, DA, and 5-HT in the
      hypothalamus and striatum. Increased levels of DA and 5-HT and their major
      metabolites DOPAC and 5-HIAA were noticed in the same region, an indication of
      increased metabolism of these amines. The increase in the 5-HT level in the
      cortex was not dose-related. Levels of NE and DA were significantly higher in the
      medulla oblongata. There was a concurrent increase in activities of tyrosine
      hydroxylase and tryptophan hydroxylase in several brain regions. The effect of
      BaP on Dopa-decarboxylase was not consistent. Monoamine oxidase was occasionally
      inhibited. Results indicate that exposure to BaP altered the steady-state levels
      of biogenic amines in various brain regions and these changes were consistent
      with the activities of metabolizing enzymes.

PMID- 1385070
TI  - Long term management of oesophageal varices.
AB  - Effective control of variceal rebleeding (secondary prophylaxis) or prevention of
      the initial bleeding (primary prophylaxis) are the main objectives of the
      treatment of portal hypertension. Endoscopic sclerotherapy is the treatment of
      choice for secondary prophylaxis, since it significantly decreases rebleeding
      and, to some extent, mortality. A combination of propranolol and sclerotherapy
      may be of benefit by decreasing postsclerotherapy rebleeding. Endoscopic variceal
      band ligation and transjugular intrahepatic shunt are emerging as useful
      alternative techniques. Devascularisation and preferably selective shunts should
      be reserved for use as salvage of sclerotherapy failures. Liver transplantation,
      if feasible, could become the ultimate therapy by controlling variceal bleeding
      and improving hepatic function. Pharmacotherapy, while not very successful for
      secondary prophylaxis, has shown promise for primary prophylaxis of variceal
      bleeding. Nonselective beta-blockers significantly decrease the rebleeding rates
      but are associated with only marginal survival benefits. beta-Blockers alone
      cannot decrease the hepatic venous pressure gradient adequately (to less than
      12mm Hg). Combination with nitrates and other drugs may prove beneficial and
      requires clinical evaluation. Endoscopic sclerotherapy and surgery have little
      role in primary prevention of variceal bleeding in patients with cirrhosis but
      need evaluation in noncirrhotic patients.

PMID- 1385072
TI  - Trace metal accumulation by the shrew Sorex araneus. I. Total body burden,
      growth, and mortality.
AB  - A laboratory feeding trial is described in which a known trace metal accumulator,
      the shrew Sorex araneus, was presented with an artificial diet containing high
      levels of copper and cadmium. Methodological difficulties relating to feeding
      trials on first generation offspring of insectivorous small mammals caught in the
      wild are described. There was no relationship between copper or cadmium intake
      and mortality during the trials. Sex differences in growth were apparently not
      influenced by metal intake. At the end of the trials there was a significant
      negative correlation between body weight and total cadmium burden. Whole body
      concentrations and burdens of cadmium increased with estimated intake. There was
      a significant negative correlation between percentage of cadmium retained as body
      burden and estimated cadmium intake. There was no discernible relationship
      between copper burden and intake.

PMID- 1385073
TI  - Trace metal accumulation by the shrew Sorex araneus. II. Tissue distribution in
      kidney and liver.
AB  - The distributions of trace metals in tissues of shrews in a series of feeding
      trials are described. The relationship between body cadmium burden and organ
      weight was directly related to differences in body weight. Organ weight expressed
      as a percentage of body weight was constant in the kidney, but was correlated
      with cadmium burden for the liver. Liver and kidney accounted for up to 80% of
      total body cadmium. The proportion of the body cadmium burden found in the kidney
      ranged from 8 to 17%. Copper and zinc concentrations in the kidney increased in
      response to cadmium accumulation. Hepatic zinc concentrations increased with
      cadmium accumulation. Exposure to a copper-contaminated diet resulted in
      increased liver copper levels. High liver concentrations were correlated with
      high kidney concentrations. At the lowest levels of exposure to metals liver and
      kidney concentrations were similar, but as exposure increased so did liver
      concentrations and much more so than in the kidney.

PMID- 1385075
TI  - Thyroid physiology impairment by malathion in the freshwater catfish Clarias
      batrachus.
AB  - Effects of malathion on serum and glandular thyroxine (T4), triiodothyronine
      (T3), the T3/T4 ratio, peroxidase activity, and extrathyroidal conversion of T4
      to T3 have been studied in the freshwater catfish Clarias batrachus during the
      prespawning and spawning phases of its annual reproductive cycle. Malathion
      inhibited T4 secretion in the kidney, but accelerated T4 synthesis in the
      pharyngeal thyroid. This pesticide also inhibited the extrathyroidal conversion
      of T4 to T3 in serum during both the studied phases.

PMID- 1385074
TI  - Investigations of the acute toxic, cytogenetic, and embryotoxic activity of
      buminafos.
AB  - The organophosphorus herbicide buminafos (O,O-dibutyl-(1-butylaminocyclohexyl)
      phosphonate) was tested for its acute toxic, cytogenetic, and embryotoxic
      activity on different strains of mice. The oral LD50 value for male NMRI mice was
      determined to be 3500 mg/kg. Single oral doses of 175, 1000, and 2000 mg/kg did
      not cause any significant enhancement in the percentage of chromosome aberrations
      in bone marrow cells of male NMRI mice. After oral administration of 500 and 1000
      mg/kg buminafos to pregnant Halle:DBA and Halle:AB mice at Days 6-15 of gestation
      no embryotoxic effects were observed. The cytogenetic inactivity of buminafos in
      the bone marrow chromosome assay corresponds to negative findings in other
      mutagenicity tests.

PMID- 1385076
TI  - Effects of polyoxyethylene (20) sorbitan monooleate on the acute toxicity of
      linear alkylbenzenesulfonate (C12LAS) to fish.
AB  - Effects of polyoxyethylene (20) sorbitan monooleate (SMOE20) on the acute
      toxicity of linear alkylbenzenesulfonate (C12LAS) to fish were investigated in
      red killifish (Orizias latipes) and carp (Cyprinus carpio). By adding
      polyoxyethylene sorbitan ester to C12LAS solution, the acute toxicity of C12LAS
      decreased. As a decreasing toxic effect of these nonionic surfactants, the
      depression of gill damage was histopathologically observed. No significant
      hematological and blood biochemical differences were observed between two tests
      using a single C12LAS solution and a mixed solution of C12LAS/SMOE20. The
      addition of SMOE20 to C12LAS decreased the incorporation of C12LAS into blood and
      each organ except spleen and gall bladder as well as the adsorption of C12LAS to
      the gill. The farther inward the phenyl position in the alkyl side chain, the
      lower the adsorption of C12LAS to gill. Since the acute toxicity of LAS phenyl
      isomers to fish was known to decrease according to the order of adsorption, these
      results suggest that the decreasing toxic effect of SMOE20 on the acute toxicity
      of C12LAS is due to depression of more toxic C12LAS adsorption on the gill.

PMID- 1385078
TI  - Effects of coal gasification slag as a substrate for the plant Cyperus esculentus
      and the worm Eisenia fetida.
AB  - A further development of the coal gasification process will result in an increase
      of the amount of coal gasification slag (CGS). As yet little is known about the
      effects of storage in uncovered dumps. If there are any environmental effects,
      they are most likely caused by accumulation of metals from the CGS or by
      unacceptable physical properties of the CGS. Growth inhibition, mortality, and
      metal accumulation were analyzed for the plant Cyperus esculentus and the worm
      Eisenia fetida on CGS substrate. Pulverized fuel ash (PFA) was used as a
      reference. Both in the substrate and in tissues the concentrations of the cations
      Cu, Ni, Pb, and Zn and the anions As, B, Cr, Mo, Sb, and Se were determined. The
      availability of anions for C. esculentus and for E. fetida is greater in PFA than
      in CGS. The extent and rate of uptake of anionic metals by the plants is on the
      whole higher in the wetland situation. The availability of metals, expressed as
      the concentration factor (CF), in most cases appears to be smaller than 1 for
      nearly all elements. In E. fetida a CF greater than 1 was found only for the
      element As, in PFA substrate and 50% CGS. In C. esculentus a CF greater than 1
      was found for B and Mo in the PFA substrate as well.

PMID- 1385077
TI  - Mercury concentration correlates with the nitrogen stable isotope ratio in the
      animal food of Papuans.
AB  - The relationships among element concentrations (Na, Mg, Al, P, K, Ca, Cr, Fe, Mn,
      Cu, Zn, Sr, total Hg, organic Hg, inorganic Hg, Pb) and stable carbon and
      nitrogen isotope ratios (13C/12C and 15N/14N) in animals consumed by the people
      called Gidra, who inhabit the lowland of Papua New Guinea, were examined. Animals
      analyzed included mammal, bird, fish, shellfish, reptile, crustacean, and insect.
      Highly significantly positive correlations were observed between total Hg
      concentrations and 15N/14N (r = 0.796), between organic Hg concentrations and
      15N/14N (r = 0.781), and between inorganic Hg concentrations and 15N/14N (r =
      0.739). This was interpreted to indicate that Hg was an element which accumulates
      in animals along the food chain. Based on the regression function of Hg on delta
      15N, the bioconcentration factor for total, organic, and inorganic Hg was
      estimated to be 5.

PMID- 1385079
TI  - Frozen algae as food for Daphnia magna Straus in toxicity testing.
AB  - As EC validity criteria for the production of Daphnia magna neonates in standard
      toxicity tests set fecundity minima which must be attained, it is important that
      culture conditions provide an adequate ration of high quality food. Maintaining a
      steady supply of fresh algae can be problematical so the possibility of using
      frozen food was investigated. The performance of three generations of D. magna
      fed on diets of fresh or frozen Chlorella was compared. There were no significant
      effects on fecundity due to food type or generation. Cumulative fecundity (over
      21 days) on fresh or frozen food exceeded 120 neonates per female and satisfied
      that EC validity criterion (60 neonates per female). In addition criteria
      relating to survival and variability were met. We conclude that frozen Chlorella
      are an acceptable substitute for fresh algae.

PMID- 1385080
TI  - Toxic effects of bleached and unbleached paper mill effluents in primary cultures
      of rainbow trout hepatocytes.
AB  - Toxic effects of unbleached (sulfate or sulfite) and bleached (sulfate) paper
      mill effluents were studied in a primary culture of rainbow trout liver cells.
      The effluents and control water from a clean area were extracted with diethyl
      ether and added to the cultures dissolved in dimethyl sulfoxide. Plasma membrane
      integrity was studied by measuring lactate dehydrogenase (LDH) leakage. The
      cellular content of glutathione (GSH) was used as an indicator of oxidative
      stress and the formation of reactive intermediates. Dose-response studies
      indicated that unbleached effluents contained more potent toxic substances than
      bleached effluents. Both unbleached and bleached effluents contained organic
      diethyl ether-extractable substances which increased cytochrome P450-dependent 7
      ethoxyresorufin-O-deethylase (EROD) activities. The inducing effects were seen at
      concentrations substantially lower than those decreasing GSH content and
      increasing LDH leakage. Possible EROD inducing substances in bleached effluents
      are chlorinated organic compounds. Inducing compounds in unbleached effluents are
      yet to be identified. Furthermore, at higher concentrations the effluents
      contained substances that inhibited the cytochrome P450 system. The results show
      that the trout primary hepatocyte cultures afford a convenient in vitro method
      for screening cytochrome P450 inducing components extracted from industrial
      effluents to investigate mechanisms by which wastewaters cause injury in cells.

PMID- 1385081
TI  - Preexposure temperature acclimation and diet as modifying factors for the
      tolerance of golden ide (Leuciscus idus melanotus) to short-term exposure to 4
      chloroaniline.
AB  - The influence of different temperature and nutrition regimes on the acute
      toxicity of 4-chloroaniline to golden ide (Leuciscus idus melanotus) was
      investigated. Acute toxicity was determined over 48 hr at 20 degrees C without
      feeding after a 2-day acclimation period. In an attempt to reveal underlying
      mechanisms accounting for diet- and temperature-related differences in the
      toxicant resistance of golden ide, biochemical and quantitative morphological
      parameters of the liver, a central organ in the xenobiotic metabolism of fish,
      were recorded throughout the 12-week acclimation period. In cold-acclimated fish,
      acute toxicity of 4-chloroaniline was 40% higher than in fish acclimated to 20
      degrees C. If compared to 20 degrees C, preacclimation to 14 degrees C was
      characterized by a lower specific growth rate, an increase of hepatic glycogen,
      and a decrease of body and liver lipid deposits. The organelle composition of
      hepatocytes was not significantly altered by temperature acclimation. For the
      nutrition experiment, commercially available diets A and B of similar crude
      composition were used. Acute toxicity of 4-chloroaniline was 60% lower with diet
      B than with diet A. If compared to diet B, diet A induced a higher specific
      growth rate and increased hepatocellular volume of endoplasmic reticulum and
      Golgi fields, whereas glycogen and lipid of the liver as well as body lipid
      contents were reduced. The toxicity of 4-chloroaniline was correlated with the
      development of the endoplasmic reticulum, the major site of biotransformation
      enzymes. A consistent correlation with lipid contents could not be established.
      Results illustrate not only that assay conditions during the actual test may
      profoundly interact with results of toxicity studies, but also that maintenance
      conditions before the test can have significant consequences on results. In order
      to improve reproducibility of the results of acute toxicity tests, more
      consideration should be given to the standardization of pretest maintenance
      conditions of fish.

PMID- 1385082
TI  - Organomercury determination in biological reference materials: application to a
      study on mercury speciation in marine mammals off the Faroe Islands.
AB  - The potential use of graphite furnace atomic absorption spectrometry (GF-AAS) for
      the organic mercury determination in marine biological tissues was evaluated.
      Following its isolation by acid extraction in toluene, organic mercury was
      recovered in aqueous thiosulfate and measured by GF-AAS. The detection limit was
      0.01 microgram Hg/g (as methyl mercury). Analyses were conducted on three
      reference standard materials certified for their methyl mercury content, DOLT-1,
      DORM-1, and TORT-1, provided by the National Research Council of Canada. The
      method resulted in very good recovery and reproducibility, indicating that GF-AAS
      can provide results comparable to those obtained by using more expensive and time
      consuming analytical techniques. The method was applied to the analysis of liver
      tissues of pilot whale specimens (Globicephala melas) from the drive fishery of
      the Faroe Islands (northeast Atlantic). The results provided useful information
      on the proportion of different mercury forms in the liver of these marine
      mammals.

PMID- 1385083
TI  - Automated interictal EEG spike detection using artificial neural networks.
AB  - Feed-forward, error-back-propagation artificial neural networks were applied to
      recognition of epileptiform patterns in the EEG. The inherent network properties
      of generalization and variability tolerance were effective in identifying wave
      forms that differed from the training patterns but still maintained
      'epileptiform' spatio-temporal characteristics. The certainty of recognition was
      measured as a continuous function with a range of 0-1. Two levels of certainty
      (0.825 and 0.900) were used to indicate recognition of spikes and sharp waves
      (SSW). An average 94.2% (+/- 7.3) of the SSW were recognized; 20.9% (+/- 22.9) of
      all recognized SSW were false-positive recognitions. The time required for
      pattern recognition was well within the time required for digitizing the analogue
      data. This study provides evidence that neural network technology is, in
      principle, an effective pattern recognition strategy for identification of
      epileptiform transients in the EEG. The analysis is sufficiently rapid to be of
      potential value as a strategy for data reduction of long recordings stored on
      bulk media.

PMID- 1385084
TI  - Development of epileptic activity induced by iron injection into rat cerebral
      cortex: electrographic and behavioral characteristics.
AB  - Unilateral injection of ferrous chloride solution into the rat sensorimotor
      cortex produced epileptic discharges in the electrocorticograms (ECoGs). The
      discharges were isolated spikes and spike and wave complexes, and the epileptic
      activity lasted for more than 12 months after the injection. Isolated spike
      activity often appeared on the left or right side of the cortex, whereas spike
      and wave complex activity appeared bilaterally. In rats showing dominant isolated
      spike activity in the secondary epileptic cortex, there was a deviation in
      somatosensory evoked potentials (SEPs). Rats showing isolated spikes and spike
      and wave complexes exhibited vibrissa tremors and head nodding. Rats showing only
      isolated spikes exhibited no abnormal behavior, but their convulsion thresholds
      to pentylenetetrazol were lowered. The results including ECoGs, SEPs, behavior
      and convulsion threshold were characterized with reference to the development of
      iron-induced epilepsy. The profiles of ECoG discharge activity and SEP
      configuration suggest that the process of iron-induced epilepsy consists of 3
      stages.

PMID- 1385085
TI  - Ontogenesis of nocturnal organization of sleep spindles: a longitudinal study
      during the first 6 months of life.
AB  - Ontogenesis of sleep spindles was studied on overnight longitudinal recordings in
      12 full-term infants at 1.5-3-4.5 and 6 months of life. Six parameters (density,
      duration, frequency, amplitude, asymmetry and asynchrony) were analyzed during
      both slow wave sleep (SII and delta) and during 5 periods of the night. Results
      show a significant increase of most parameters between 1.5 and 3 months of age.
      All spindle patterns developed quite rapidly during the first 3 months of
      infancy, possibly reflecting developmental changes in thalamo-cortical structures
      and maturation of the physiological system that produces spindles. The density of
      12-14 Hz spindle frequency was higher in stage II when compared to stage delta,
      as in adults. Our data confirm previous reports on spindle ontogenesis and give a
      more complete aspect of this ontogenesis in relation to sleep development. Three
      months of age appeared to be a turning point in maturational processes and might
      reflect changes in central nervous system activity and behavior which take place
      during that period. Sleep spindle evolution seems to be an accurate reflection of
      the slow wave sleep (SWS) development, and our results are discussed in terms of
      the developmental aspect of SWS production and characterization of sleep stages
      in young infants. Concordance between quantitative aspects and nocturnal
      organization leads us to consider that the individualization of slow wave sleep
      (SWS) in infants occurs from 4.5 months of life.

PMID- 1385086
TI  - Changes in cortical negative DC shifts due to different motor task conditions.
AB  - The experiments were performed to study the relationship between motor
      performance and DC potential curves recorded by scalp electrodes. Accordingly, we
      studied the influence of different movements (e.g., unilateral versus bilateral,
      simple versus complex, active versus passive, phasic versus tonic muscle
      activity) on negative DC potentials. Our results confirm that spatial
      distributions of DC potential maxima can be used as an indicator of the
      activation of distinct cortical areas. Furthermore, evidence is presented that
      some motor tasks have a greater influence on the magnitude of surface
      electronegativity than others. (1) Phasic muscle activity revealed a
      significantly larger potential size than tonic. (2) Performance of a complex
      finger movement task elicited an increased surface electronegativity compared
      with performance of a simple task. (3) No significant differences in potential
      size were found between left (untrained) and right (skilled) hand use during the
      performance of the same complex motor task. (4) This was also true for the
      performance of an active and a passive finger movement task, indicating that, at
      least in simple motor tasks, somatosensory afferents significantly contribute to
      the recorded potential curve.

PMID- 1385087
TI  - Event-related potentials to repetition and change of auditory stimuli.
AB  - The major intent of this study was to compare the role of stimulus repetition and
      change in the elicitation of the MMN, an ERP component specific to stimulus
      change, and N2b, usually partially overlapping the MMN when stimuli are attended.
      Event-related potentials were recorded in one set of conditions where subjects
      ignored the stimuli and read a book, and in another set of conditions where
      subjects counted stimuli designated as targets. Stimuli were delivered in 4 ways,
      the common feature between all these conditions being the occurrence of
      infrequent events at a probability of 0.20: (1) an oddball paradigm with 1
      deviant, (2) an oddball paradigm with 2 deviants, each with a probability of
      0.10, (3) a regular alternation of tones of 2 pitches where either of the 2 tones
      infrequently repeated (P = 0.20), and (4) a random presentation of tones of 5
      different pitches, where any of the 5 tones infrequently repeated (P = 0.20). In
      the count conditions, the infrequent events were designated as targets. It was
      found that the MMN was elicited by stimulus change and not stimulus repetition in
      the ignore and count conditions, whereas the N2b was elicited by both stimulus
      changes and repetitions in the count conditions. It was also possible, in the
      count conditions, to disentangle the part of the late positive complex which is
      related to stimulus deviation and the part which is related to stimulus
      significance (target).

PMID- 1385088
TI  - On the evidence of auditory evoked magnetic fields as an objective measure of
      tinnitus.
AB  - The purpose of the present study was to determine the utility of auditory evoked
      magnetic fields as an objective measure of tinnitus. The auditory evoked magnetic
      fields of 14 patients with tinnitus and of 14 sex- and age-matched controls were
      measured by means of a 7-channel BTI neuromagnetometer. Stimuli were 1 kHz tone
      bursts presented randomly. Tinnitus patients and controls were similar with
      respect to latencies and amplitudes of the N100m and P200m, and with respect to
      the locations and moments of the equivalent current dipoles. The present study
      could not support the notion that specific abnormalities of the auditory evoked
      magnetic fields are characteristic of patients with tinnitus.

PMID- 1385089
TI  - Modelling magnetic coil excitation of human cerebral cortex with a peripheral
      nerve immersed in a brain-shaped volume conductor: the significance of fiber
      bending in excitation.
AB  - To help elucidate some basic principles of magnetic coil (MC) excitation of
      cerebral cortex, a model system was devised in which mammalian phrenic nerve, or
      amphibian sciatic nerve with its branches was suspended in appropriate Ringer's
      solution in a human brain-shaped volume conductor, an inverted plastic skull. The
      nerve was recorded monophasically out of the volume conductor. The site of nerve
      excitation by the MC was identified by finding where along the nerve a bipolar
      electrical stimulus yielded a similar action potential latency. MC excitation of
      hand-related corticospinal (CT) neurons was modelled by giving the distal end of
      nerve attached to the lateral skull an initial radial (perpendicular) trajectory,
      with subsequent bends towards the base and posterior part of the skull; this
      nerve was optimally excited by a laterally placed figure 8 or round MC when the
      induced electric field led to outward membrane current at the initial bend. By
      contrast, nerve given a trajectory modelling CT neurons related to the foot was
      optimally excited when the coil windings were across the midline, but again when
      membrane current flowed outward at the first bend. Corticocortical fibers were
      modelled by placing the nerve in the anteroposterior axis lateral to the midline;
      with the round MC vertex-tangentially orientated, optimal excitation occurred at
      the bend nearest the interaural line, i.e., near the peak electric field. The
      findings emphasize the importance of orientation and direction of current in the
      MC and fiber bends in determining nerve excitation. The findings in the
      peripheral nerve-skull model help explain (1) why lateral and vertex-tangentially
      orientated MCs preferentially excite arm-related CT neurons directly and
      indirectly (through corticocortical fibers), respectively, and (2) why the MC
      orientations for optimally exciting directly arm and leg-related CT neurons
      differ.

PMID- 1385090
TI  - Facilitation of motor evoked potentials by somatosensory afferent stimulation.
AB  - The effect of an electrically induced peripheral afferent volley upon electrical
      and magnetic motor evoked potentials (MEPs) from muscles of the upper and lower
      extremities was studied in 16 healthy volunteers. A standard conditioning-test (C
      T) paradigm was employed whereby the test stimulus (transcranial electric or
      magnetic) was applied at random time intervals, from 10 msec prior to 90 msec
      after the conditioning stimulus (peripheral nerve stimulus). MEP amplitude
      facilitation was observed for the majority of the upper extremity muscles tested
      at two distinct periods, one occurring at short, and the other at long C-T
      intervals. This bimodal trend of MEP facilitation was found to be equally as
      prominent in the lower extremity muscles tested. The period of short C-T interval
      facilitation is consistent with modifications in the spinal excitability of the
      segmental motoneuron pool. On the other hand, the period of long C-T interval
      facilitation is suggested to be due to alterations in excitability of the motor
      cortex as a result of the arrival of the orthodromic sensory volley. Although
      most pronounced in muscles innervated by the nerve to which the conditioning
      stimulus was applied, this bimodal facilitatory effect was also observed in
      adjacent muscles not innervated by the stimulated nerve. Qualitatively, the
      conditioned MEPs from the upper and lower extremities responded similarly to both
      electrical and magnetic trans-cranial stimulation. In addition, our study
      demonstrates that the C-T paradigm has potential for use in the assessment of
      spinal and cortical sensorimotor integration by providing quantitative
      information which cannot be obtained through isolated assessment of sensory
      and/or motor pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385091
TI  - The contribution of magnetic stimulation of the motor cortex to the diagnosis of
      cervical spondylotic myelopathy. Correlation of central motor conduction to
      distal and proximal upper limb muscles with clinical and MRI findings.
AB  - Magnetic stimulation of the motor cortex and cervical spine was performed on 24
      patients with cervical spondylotic myelopathy documented by MRI. Compound motor
      action potentials (CMAPs) were recorded from the biceps and thenar muscles to
      study the central motor pathways of two different myotomes, C5-C6 and C8-D1.
      Central motor conduction was abnormal in all 24 patients for thenar muscles and
      in 5 patients for biceps brachii. In patients with a single compression level,
      central motor conduction abnormalities were confined to the myotomes caudal to
      the site of compression documented by MRI, in both proximal and distal upper limb
      muscles in the patients with upper spondylotic compression, and in distal muscles
      only in the patients with lower compression. In the patients with multilevel
      compression, central motor conduction time was abnormal for thenar muscles and
      always normal for the biceps muscle, but its mean value was significantly greater
      than in the control subjects, suggesting a slight involvement of central motor
      pathways for proximal upper limb muscles and major damage of the lower cervical
      segments. Owing to their high degree of sensitivity, central motor conduction
      studies may be of considerable value in the functional assessment of central
      motor pathways in cervical spondylotic myelopathy.

PMID- 1385092
TI  - The relation between functional deficits, motor and sensory conduction times and
      MRI findings in syringomyelia.
AB  - Opinions about the relation between the dimensions of the syrinx and the severity
      and distribution of symptoms in patients with syringomyelia are controversial.
      Therefore, this study investigates the relation of clinical symptoms, a
      disability score, quantified (1- and 2-dimensional) radiological findings
      (magnetic resonance imaging, MRI) and electrophysiological data (somatosensory
      and motor evoked potentials) in 22 patients with syringomyelia. There was a close
      relation between clinical symptoms and electrophysiological data. By both
      electrophysiological methods subclinical deficits could be detected. Furthermore,
      the results disclosed that the clinical symptoms, the degree of disability and
      the duration of the disease are not related to the dimensions of the syrinx or
      the electrophysiological results obtained by investigating the long ascending and
      descending spinal tracts of the lower limbs. Our findings suggest that, besides
      the syrinx, other factors not directly visible in the MRI are responsible for the
      development and progress of clinical symptoms.

PMID- 1385093
TI  - The influence of the shape of mechanical stimuli on muscle stretch reflexes and
      SEP.
AB  - Stretching of human thenar muscle was carried out using mechanical stimuli of
      different amplitudes and velocities in 50 normal subjects. Amplitudes of early M1
      and late M2 reflex responses as well as cortical evoked potentials were recorded.
      M1 and M2 increased with a larger mechanical stimulus. Steeper mechanical stimuli
      generated larger M1 amplitudes, whereas M2 remained unaffected. Amplitudes of
      early cortical evoked potentials increased with increase of both rise-time and
      amplitude of muscle stretch. The shape of the mechanical stimulus is critical for
      the resulting reflex response. The different behaviours of M1 and M2 with
      increasing stimulus velocity are in favour of their different origins. Our
      results support a participation of slowly conducting muscle spindle afferents in
      the generation of the late M2 response in distal human hand muscles.

PMID- 1385094
TI  - Recovery functions of common peroneal, posterior tibial and sural nerve
      somatosensory evoked potentials.
AB  - We studied recovery functions of the somatosensory evoked potentials (SEPs) of
      common peroneal (CPN), posterior tibial (PTN) and sural nerves (SN) using a
      paired conditioning-test paradigm. The interstimulus interval (ISI) of paired
      stimuli ranged from 2 to 400 msec. In all SEPs with ISIs of 12-20 msec, the
      amplitude recovery was close to or beyond 100% of the control response, though
      their latencies and wave forms were not the same as the control. Further
      increases of the ISI resulted in significant depression of SEP (late phase
      suppression), most markedly in CPN, and less prominently in SN-SEP. With a longer
      than 50 msec ISI there was progressive recovery of SEP, but full recovery
      differed depending on the nerve stimulated; 400 msec ISI was required for CPN-,
      250 msec for PTN- and 100 msec for SN-SEP. The peroneal nerve block by local
      anesthetic injected just distal to the stimulus electrodes abolished the late
      phase SEP suppression observed before the nerve block. These findings suggest
      that the late phase SEP suppression is attributable to the "secondary" afferents
      as a result of activation of peripheral receptors (muscle, joint and/or
      cutaneous) by the efferent volley initiated from the stimulus point. The greater
      and longer duration of peripheral receptor activation in CPN than in PTN or SN
      stimulation could explain the more pronounced and the longer duration of late
      phase suppression in CPN-SEP.

PMID- 1385095
TI  - After-potentials and control of repetitive firing in human motoneurones.
AB  - Characteristics of motoneurone after-potentials in man were derived from the
      recovery curve of motoneurone excitability after a single discharge evoked by
      threshold stimulation of Ia afferents or by gentle voluntary muscle contraction.
      The motoneurone excitability was estimated by the firing index of a single motor
      unit whose potentials were recorded by needle electrodes. The soleus (a slow
      muscle) and the flexor carpi ulnaris (a fast muscle) were investigated. The
      duration of motoneurone after-hyperpolarization of the soleus evaluated by this
      method ranged between 145 and 255 msec; for the flexor carpi ulnaris it was 55
      150 msec. In some motoneurones of the fast muscle, an early short-lasting
      recovery of excitability (within 5-20 msec after a discharge) was revealed. It
      was accounted for by delayed depolarization of the motoneurone. The relationship
      between after-potentials and the characteristics of repetitive firing of
      motoneurones activated by weak voluntary muscle contraction was analysed. It was
      observed that the motoneurones with early excitability recovery were capable of
      firing double discharges with a 5-15 msec interspike interval. It was found also
      that the minimal firing rate of motoneurones (up to 3.1-5.2 imp/sec in the soleus
      and 3.8-9.0 imp/sec in the flexor carpi ulnaris) was not correlated with the
      after-hyperpolarization duration. This differs from the results obtained for
      cat's motoneurones under intracellular stimulation. The findings suggest that
      after-hyperpolarization is not the only leading mechanism controlling the low
      firing rate of motoneurones under conditions of their natural activity in man.

PMID- 1385097
TI  - Regulation of galanin gene expression in the rat anterior pituitary gland by the
      somatostatin analog SMS 201-995.
AB  - In addition to inducing pituitary tumors in rats, estrogen (E2) markedly
      increases galanin and PRL gene expression. We previously showed that galanin
      secretion from pituitary cells in vitro is inhibited by dopamine and somatostatin
      and stimulated by TRH. The objectives of these in vivo studies were to assess
      whether the long-acting somatostatin analog SMS 201-995 alters 1) immunoreactive
      galanin or PRL levels in the anterior pituitary, neurointermediate lobe,
      hypothalamus, or plasma, 2) pituitary galanin and PRL mRNA levels, and 3) the
      development of E2-induced pituitary tumors. Ovariectomized Fischer 344 rats were
      implanted with E2-filled or empty Silastic capsules and treated with or without
      SMS 201-995 (1.5 mg) via Alzet miniosmotic pumps. Two or 6 weeks later,
      immunoreactive galanin and PRL levels were determined by RIA. In ovariectomized
      rats, the somatostatin analog lowered the anterior pituitary content of galanin
      by 50%, but had no effect on PRL concentrations. E2 increased galanin and PRL
      levels in the anterior pituitary by 220- and 4-fold, respectively. Concomitant E2
      and SMS 201-995 treatment further increased galanin and PRL in the anterior
      pituitary by 60-80%, but decreased plasma galanin and PRL levels. Likewise, the
      administration of SMS 201-995 for 2 and 6 weeks inhibited the E2-induced growth
      of the anterior pituitary. Galanin and PRL mRNA levels were quantified by
      solution hybridization. Galanin mRNA levels were reduced to undetectable levels
      in ovariectomized rats treated with SMS 201-995. Furthermore, a 10-fold increase
      in galanin mRNA levels seen in the presence of E2 was inhibited 80% by SMS 201
      995. PRL mRNA levels in E2-treated rats were unchanged by SMS 201-995. We
      conclude that SMS 201-995 1) lowers plasma galanin and PRL levels in E2-treated
      rats, 2) elevates the anterior pituitary contents of galanin and PRL in E2
      exposed rats, probably through decreased secretion of the hormones, and 3)
      reduces galanin mRNA levels in E2-treated and untreated ovariectomized rats.
      Overall, these results establish the differential regulation of galanin and PRL
      gene expression in vivo by SMS 201-995. Moreover, the data demonstrate that
      somatostatin receptor agonists may have therapeutic potential for some
      prolactinomas.

PMID- 1385096
TI  - Evidence for a novel insulin-like growth factor (IGF)-dependent protease
      regulating IGF-binding protein-4 in dermal fibroblasts.
AB  - The mechanisms by which insulin-like growth factors (IGFs) reduce IGF-binding
      protein-4 (IGFBP-4) levels in cellular conditioned media are poorly understood.
      The effect of IGFs on IGFBP-4 levels in fibroblast conditioned media is not
      mediated via the type 1 or type 2 cellular IGF receptors, and the IGFs exert
      little or no effects on IGFBP-4 messenger RNA levels in human adult fibroblasts
      or in rat neuroblastoma cells. To determine whether the effects of IGFs on IGFBP
      4 might be exerted through alterations in IGFBP-4 degradation, we incubated cell
      free, fibroblast-conditioned media from either sheep or human dermal fibroblasts
      with or without IGF-I, IGF-II (each 1 microgram/ml), or insulin (10
      micrograms/ml) for 72 h at 37 C. Samples were then analyzed by Western ligand
      blot using radiolabeled IGFs and by immunoblotting using a polyclonal antisera to
      human IGFBP-4. In the absence of IGFs, no apparent changes in the basal
      concentrations of the various IGFBPs were observed. In contrast, incubation of
      media with IGFs caused a 70-80% reduction in levels of both sheep and human IGFBP
      4, whereas incubation with insulin was without effect. Similarly, incubation of
      cell-free conditioned media containing recombinant human IGFBP-4 with IGF-I
      caused a reduction in detectable levels of the 28K protein. The decrease in IGFBP
      4 levels was accompanied by the appearance of an immunoreactive approximate 17
      20K fragment that did not bind radiolabeled IGFs by ligand blot. The IGF
      dependent decrease in IGFBP-4 was prevented by coincubation of the media with
      serine protease inhibitors, EDTA, or 1,10-phenanthrolene, suggesting that IGFs
      may activate an IGFBP-4 specific metallo-serine protease present in fibroblast
      conditioned media. Alternatively, binding of IGF-I or -II to IGFBP-4 may enhance
      the susceptibility of IGFBP-4 to proteolytic degradation. The demonstration that
      IGF-I and IGF-II can promote directly the proteolytic degradation of IGFBP-4 into
      fragments that do not bind IGFs provides a novel mechanism by which the IGFs may
      increase their own availability and/or activity in biological fluids.

PMID- 1385098
TI  - Components of signaling pathways for insulin and insulin-like growth factor-I in
      muscle myoblasts and myotubes.
AB  - To survey and compare the signaling pathways from the insulin and insulin-like
      growth factor-I (IGF-I) receptors in undifferentiated and differentiated muscle
      cells, we examined the phosphotyrosine (Ptyr)-containing polypeptides elicited in
      L6 and Sol8 myoblasts and myotubes by the combination of insulin and IGF-I. These
      polypeptides were detected by immunoblotting with antibodies against Ptyr. In the
      L6 myoblasts and myotubes and the Sol8 myoblasts, Ptyr polypeptides of
      approximately 240, 175, 115, 100, 41, and 37 kilodaltons (kDa) appeared in
      response to insulin-IGF-I. With the Sol8 myotubes, the 240-, 175-, and 37-kDa
      Ptyr polypeptides were detected in basal cells, and only the Ptyr content of the
      175-kDa one increased in response to insulin-IGF-I. The polypeptides of 175, 41,
      and 37 kDa were tentatively identified as the insulin receptor substrate 1 (IRS1)
      and extracellular signal-regulated kinases 1 and 2 (ERK1 and -2), respectively,
      by immunoblotting with antibodies specific for these proteins, and the 115- and
      100-kDa polypeptides are probably the beta-subunits of the insulin and IGF-I
      receptors. The amounts of IRS1, ERK1, and ERK2 were roughly the same in the L6
      and Sol8 myoblasts and myotubes. Thus, differentiation of the myoblasts to
      myotubes was not accompanied by the detectable appearance of new insulin-IGF-I
      elicited Ptyr polypeptides or marked changes in the amounts of known participants
      in their signaling pathways.

PMID- 1385099
TI  - Basic fibroblast growth factor modulates insulin-like growth factor-I, its
      receptor, and its binding proteins in hypothalamic cell cultures.
AB  - Interactions between different growth factors may be important in the regulation
      of cell growth and differentiation in the nervous system. For instance, basic
      fibroblast growth factor (bFGF) regulates neuroblast division through a mechanism
      probably involving insulin-like growth factor-I (IGF-I). In this regard, we
      previously found that simultaneous addition of both factors produces an additive
      effect on survival and differentiation of hypothalamic neuronal and glial cells
      in culture. To further analyze these interactions, we explored the influence of
      bFGF on IGF-I, its membrane receptor, and its binding proteins in hypothalamic
      cells. We also tested the effects of IGF-I on its own receptor and binding
      proteins (IGFBPs) to determine the specificity of bFGF's actions. Treatment of
      neuronal and glial cultures with bFGF produced an increase in IGF-I receptors,
      without changing their affinity, together with an increase in the apparent M(r)
      of the receptor. On the other hand, IGF-I elicited a down-regulation of its own
      receptor in both neurons and glia, without modifying its affinity. Treatment with
      bFGF also produced a marked differential effect on the IGFBPs secreted by the
      cells. While IGFBP levels in neuronal cultures were greatly increased by bFGF,
      their production by glial cells was inhibited. On the other hand, IGF-I increased
      the amount of IGFBPs in both types of cells. Finally, addition of bFGF to the
      cultures elicited a dose-dependent increase in the release of IGF-I to the
      medium, but only a moderate increase in cellular IGF-I content, in both neurons
      and glia. We conclude that bFGF strongly modulates IGF-I, its receptors, and its
      binding proteins in the two major cell types of the hypothalamus. These findings
      reinforce the possibility that IGF-I and/or its receptors and binding proteins
      are involved in the trophic effects of bFGF on developing brain cells.

PMID- 1385100
TI  - Modulation of growth-related gene expression and growth inhibition by cyclic
      adenosine 3',5'-monophosphate-elevating agents in the insulin-producing cell line
      beta TC1.
AB  - We studied the involvement of the cAMP pathway in the regulation of beta TC1 cell
      growth with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX)
      and the activator of adenylate cyclase forskolin. We examined the effect of the
      increase in cAMP content on the serum-induced resumption of the cell cycle of
      quiescent cells. IBMX and forskolin both inhibited the mitogenic effect of serum
      in a concentration-dependent manner. Intracellular cAMP levels were,
      respectively, enhanced 3.0- and 8.6-fold by IBMX (0.5 mM) and forskolin (20
      microM) within 1 h. IBMX and forskolin were also inducers of insulin release,
      indicating that the growth-arrested beta TC1 cells have retained the essential
      characteristics of the normal differentiated beta-cells. The effects of IBMX and
      forskolin were correlated with a modulation of cell cycle-related gene
      expression. IBMX induced expression of the c-fos gene, which was further enhanced
      by the simultaneous addition of serum, whereas forskolin alone elicited maximal
      induction of this gene. Interestingly, c-jun expression was only enhanced with
      forskolin. We also studied the effects of IBMX and forskolin on the expression of
      the simian virus-40 T-antigen controlled by the rat insulin II promoter in beta
      TC1 cells. IBMX and forskolin inhibited the serum-induced accumulation of simian
      virus-40 T-antigen mRNA in quiescent as well as exponentially growing beta TC1
      cells.

PMID- 1385101
TI  - Regulation of rat insulin-like growth factor-binding protein-1: the effect of
      insulin-induced hypoglycemia.
AB  - Rat insulin-like growth factor-binding protein-1 (rIGFBP-1) was purified from
      H4IIE rat hepatoma cells by IGF-I affinity chromatography and reverse-phase HPLC.
      A rabbit antiserum (B2) was raised to rIGFBP-1 and a RIA established.
      Immunoreactive IGFBP-1 was present in rat amniotic fluid and in the medium
      conditioned by isolated rat hepatocytes and HTC rat hepatoma cells. To study the
      effect of hypoglycemia, fasting female Wistar rats were anesthetized and
      cannulated for multiple venous sampling after the administration of insulin or
      saline. Serum IGFBP-1 rose in adrenal intact rats from < 0.1 micrograms/ml to a
      maximum of 1.41 +/- 0.23 micrograms/ml approximately 120 min after insulin
      administration. Compared to adrenal-intact rats, adrenalectomized animals
      demonstrated a delayed rIGFBP-1 response to hypoglycemia and did not appear to
      have reached a maximum at 180 min. A slow rise in rIGFBP-1 levels throughout the
      sampling period was seen after saline injection in both adrenal-intact and
      adrenalectomized animals. Glucose, corticosterone, rat insulin, and human insulin
      levels were measured and none, alone, appeared responsible for the observed
      rIGFBP-1 responses. We conclude that 1) rIGFBP-1 is stimulated in response to
      hypoglycemia in a similar manner to glucose counterregulatory hormones, 2) an
      adrenal factor is required for an early rIGFBP-1 response to hypoglycemia, and 3)
      neither circulating glucose nor insulin levels, alone, are responsible for the
      observed patterns of response.

PMID- 1385102
TI  - In vitro androgenic induction of a major protein in epithelial cell subcultures
      from mouse vas deferens.
AB  - Pure epithelial cell cultures, obtained from primary culture of vas deferens
      tissue collected from 20- to 30-day-old mice, were amplified by subculturing the
      cells over 3T3 feeder layer in a serum-free defined medium. Adhesion and
      proliferation of epithelial cells did not require androgens, but a minimal
      concentration of 5.10(-7) M hydrocortisone. In that system, epithelial cells
      expressed cytokeratin but failed to produce the tissue specific mouse vas
      deferens protein (MVDP) in response to androgens. Various culture procedures and
      medium compositions were assayed for induction of MVDP expression. Culture onto
      microporous membrane inserts, which allow polarization of cells, is absolutely
      required for androgenic induction of MVDP. Androgen action did not require the
      presence of hydrocortisone, insulin, triiodothyronine, pituitary extracts,
      epidermal growth factor and acetylcholine. A minimal supplemented medium was then
      defined in which the expression of MVDP by epithelial cells in response to
      androgens was dose dependent. It has also been shown that this response at each
      concentration of dihydrotestosterone was heterogeneous at individual cell level.
      Highly reproducible results were obtained from epithelial cell cultures between
      8th to 16th passages, showing that subcultured cells have maintained their
      ability to differentiate and express specialized functions.

PMID- 1385103
TI  - Somatostatin analog induces insulin-like growth factor binding protein-1 (IGFBP
      1) expression in human hepatoma cells.
AB  - As the somatostatin analog octreotide suppresses pituitary GH secretion and
      circulating IGF-1 levels, we examined its effects on human hepatoma (hep G2)
      cells which selectively express IGFBP-1. Octreotide (60 nM) stimulated IGFBP-1 up
      to 4.1-fold (p < 0.001 after 24 hrs). Induction of IGFBP-1 was first detectable
      after 12 hrs of 6 nM octreotide (1.5-fold, p < 0.03), and was confirmed by ligand
      blotting. Cholera toxin and forskolin induced IGFBP-1 independently and were also
      additive with octreotide. IGFBP-1 mRNA expression was induced 2.7-fold by
      octreotide. Thus, octreotide induces basal and stimulated IGFBP-1 in hepatocytes
      independently of insulin and GH. As IGFBP-1 may regulate peripheral IGF-1 action,
      induction of IGFBP-1 represents a novel pituitary-independent mechanism for
      octreotide action.

PMID- 1385104
TI  - Prorenin-renin axis in synovial fluid in patients with rheumatoid arthritis and
      osteoarthritis.
AB  - This study was undertaken 1) to determine whether or not renin is present in
      synovial fluid in patients with rheumatoid arthritis and osteoarthritis, and, if
      present, 2) to investigate whether it is synthesized in synovial fluid, or it is
      only transported from the circulation into the synovial cavity. The active renin
      concentration (indirect) was measured with angiotensin I radioimmunoassay kits.
      Inactive renin was converted into active renin with Sepharose-bound trypsin. Both
      active and inactive forms of renin were found in synovial fluid. They were
      significantly higher in patients with rheumatoid arthritis (n = 9) than in those
      with osteoarthritis (n = 16). In plasma, the concentration of inactive renin was
      significantly higher (P less than 0.001) in the former. Albumin, transferrin,
      alpha 2-macroglobulin, ceruloplasmin and immunoglobulins G and M were also found
      in synovial fluid. In each disease, a plot of the log ratio of synovial fluid to
      the serum concentration against the log molecular weight of each protein gave an
      approximately straight line curve, suggesting that these proteins are derived
      from the circulation and are transported into the synovial cavity. In contrast,
      the ratio of synovial fluid to plasma concentrations of active renin was
      significantly higher than that predicted on the basis of the above-mentioned
      interrelationships in both diseases, whereas the ratio of inactive renin was
      significantly lower. These findings suggest that 1) inactive and active renin are
      filtered into the synovial fluid from the circulation, and that 2) inactive renin
      is converted into the active form in the fluid.

PMID- 1385105
TI  - Localized non-Hodgkin's lymphoma of the adrenal and thyroid glands.
AB  - A case of immunoblastic lymphoma, involving only the thyroid and the adrenal
      glands, is presented. The patient had clinical symptoms and findings of Addison's
      disease, and computed tomography (CT) demonstrated bilateral adrenal tumoral
      enlargement. He also had euthyroid diffuse multinodular goiter. The diagnosis of
      the patient was based on the cytological examination of the aspiration materials
      from both endocrine glands. The patient received "m-BNCOD" chemotherapy regimen
      and replacement therapy for Addison's disease. At the end of three courses, a
      partial response was obtained.

PMID- 1385106
TI  - The orientation of transition moments of dye molecules used in fluorescence
      studies of muscle systems.
AB  - Fluorescence and phosphorescence depolarization techniques can provide
      information on orientational order and rotational motion of crossbridges in
      muscle fibres. However the depolarization experiment monitors the orientation and
      motion of the crossbridges indirectly. The changes in depolarization arise from a
      change in the orientation of the transition dipoles of the dye attached to the
      crossbridge. In order to extract the physiologically relevant orientations from
      the data it is therefore necessary to characterize the orientation of the dye
      molecule relative to the crossbridge and the orientation of the transition
      moments in the frame of the dyes. The dyes 1,5-I-AEDANS and eosin-5-maleimide are
      commonly used for labelling the crossbridge in muscle fibres. The orientations of
      the absorption and fluorescence emission dipoles of these two dyes in the
      molecular frame were determined. Angle resolved fluorescence depolarization
      experiments on the dyes, macroscopically aligned in a stretched polymer matrix of
      poly vinyl alcohol, were carried out. The data were analyzed in terms of an
      orientational distribution of the dye molecules in the film and the orientations
      of the absorption and emission dipoles in the frame of the dye molecule.
      Experimental data, obtained from a given sample at different excitation
      wavelengths, were analyzed simultaneously in a global target approach. This leads
      to a reduction in the number of independent parameters optimized by the non
      linear least squares procedure.

PMID- 1385108
TI  - Interferons as hormones of pregnancy.

PMID- 1385107
TI  - The roles of serine and threonine sidechains in ion channels: a modelling study.
AB  - The ion channel of the nicotinic acetylcholine receptor (nAChR) is believed to be
      lined by transmembrane M2 helices. A "4-8-12" sequence motif, comprising serine
      (S) or threonine (T) residues at positions 4, 8 and 12 of M2, is conserved
      between different members, anion and cation selective, of the nAChR superfamily.
      Parallel bundles of 4-8-12 motif-containing helices are considered as simplified
      models of ion channels. The relationship between S and T sidechain conformations
      and channel-ion interactions is explored via evaluation of interaction energies
      of K+ and of Cl- ions with channel models. Energy calculations are used to
      determine optimal chi 2 (C alpha-C beta-O gamma-H gamma) values in the presence
      of K+ or Cl- ions. 4-8-12 motif-containing bundles may form favourable
      interactions with either cations or anions, dependent upon the chi 2 values
      adopted. Parallel-helix and tilted-helix bundles are considered, as are
      heteromeric models designed to mimic the Torpedo nAChR. The main conclusion of
      the study is that conformational flexibility at chi 2 enables both S and T
      residues to form favourable interactions with anions or cations. Consequently,
      there is apparently no difference between S and T residues in their interactions
      with permeant ions, which suggests that the presence of T vs. S residues within
      the 4-8-12 motif is not a major mechanism whereby anion/cation selectivity may be
      generated. The implications of these studies with respect to more elaborate
      models of nAChR and related receptors are considered.

PMID- 1385109
TI  - Determination of resistant starch in vitro with three different methods, and in
      vivo with a rat model.

PMID- 1385110
TI  - Using coomassie blue to stabilize H2O2-guaiacol stained peroxidases on
      polyacrylamide gels.
AB  - Shimoni and Reuveni [1] have reported a procedure which uses Coomassie Brilliant
      Blue R-250 staining and destaining to stabilize H2O2-guaiacol stained peroxidases
      on polyacrylamide gels and at the same time detects nonspecific protein bands.
      The procedure has the advantage that the otherwise orange and unstable peroxidase
      bands are visualized as blue bands and it, therefore, facilitates laser
      densitometry of electrophoretically separated peroxidases. In the modification of
      the procedure reported here, the Coomassie staining reagent was adjusted and the
      destaining step was eliminated. The modified procedure has added advantages: it
      simplifies the procedure, increases the consistency of the results across gels,
      prevents or reduces the staining of nonspecific proteins, and still gives
      excellent resolution of stable bands which can be used to quantify peroxidase
      activity.

PMID- 1385111
TI  - Fibroblast growth factor receptor-4 shows novel features in genomic structure,
      ligand binding and signal transduction.
AB  - Fibroblast growth factor (FGF) receptor (FGFR) gene family consists of at least
      four receptor tyrosine kinases that transduce signals important in a variety of
      developmental and physiological processes related to cell growth and
      differentiation. Here we have characterized the binding of different FGFs to FGFR
      4. Our results establish an FGF binding profile for FGFR-4 with aFGF having the
      highest affinity, followed by K-FGF/hst-1 and bFGF. In addition, FGF-6 was found
      to bind to FGFR-4 in ligand competition experiments. Interestingly, the FGFR-4
      gene was found to encode only the prototype receptor in a region where both FGFR
      1 and FGFR-2 show alternative splicing leading to differences in their ligand
      binding specificities and to secreted forms of these receptors. Ligands binding
      to FGFR-4 induced receptor autophosphorylation and phosphorylation of a set of
      cellular polypeptides, which differed from those phosphorylated in FGFR-1
      expressing cells. Specifically, the FGFR-1-expressing cells showed a considerably
      more extensive tyrosine phosphorylation of PLC-gamma than the FGFR-4-expressing
      cells. Structural and functional specificity within the FGFR family exemplified
      by FGFR-4 may help to explain how FGFs perform their diverse functions.

PMID- 1385112
TI  - The multidrug resistance and cystic fibrosis genes have complementary patterns of
      epithelial expression.
AB  - The cystic fibrosis gene product, CFTR, and the multidrug resistance P
      glycoprotein (encoded by the MDR1 gene) are structurally related proteins and
      both are associated with epithelial chloride channel activities. We have compared
      their cell-specific expression in the rat by in situ hybridization. In all
      tissues examined the two genes were found to have complementary patterns of
      expression, demonstrating exquisite regulation in both cell-specific and temporal
      fashions. Additionally, a switch in expression from one gene to the other was
      observed in certain tissues. For example, expression in the intestine switches
      from CFTR to MDR1 as the cells migrate across the crypt-villus boundary. A switch
      from CFTR to MDR1 expression was also observed in the uterine epithelium upon
      pregnancy. These data suggest that CFTR and P-glycoprotein serve analogous roles
      in epithelial cells and provide additional evidence that P-glycoprotein has a
      physiological role in regulating epithelial cell volume. The patterns of
      expression suggest that the regulation of these two genes is coordinately
      controlled.

PMID- 1385113
TI  - The atypical M2 segment of the beta subunit confers picrotoxinin resistance to
      inhibitory glycine receptor channels.
AB  - Purified preparations of the inhibitory glycine receptor (GlyR) contain alpha and
      beta subunits, which share homologous primary structures and a common
      transmembrane topology with other members of the ligand-gated ion channel
      superfamily. Here, a beta subunit-specific antiserum was shown to precipitate the
      [3H]strychnine binding sites localized on alpha subunits from membrane extracts
      of both rat spinal cord and mammalian cells co-transfected with alpha and beta
      cDNAs. Further, inhibition of alpha homo-oligomeric GlyRs by picrotoxinin, a non
      competitive blocker of ion flow, was reduced 50- to 200-fold for alpha/beta
      hetero-oligomeric receptors generated by cotransfection. Site-directed
      mutagenesis identified residues within the second predicted transmembrane segment
      (M2) of the beta subunit as major determinants of picrotoxinin resistance. These
      data implicate the M2 segment in blocker binding to and lining of the GlyR
      chloride channel.

PMID- 1385114
TI  - The human T cell antigen gp39, a member of the TNF gene family, is a ligand for
      the CD40 receptor: expression of a soluble form of gp39 with B cell co
      stimulatory activity.
AB  - Signals delivered to B cells via CD40 can synergize with those provided by other
      B cell surface receptors to induce B cell proliferation and antibody class
      switching as well as modulate cytokine production and cell adhesion. Recently, it
      has been shown that the ligand for CD40 is a cell surface protein of
      approximately 39 kDa expressed by activated T cells, gp39. Here we report on the
      isolation and characterization of a cDNA clone encoding human gp39, a type II
      membrane protein with homology to TNF, and the construction and characterization
      of a soluble recombinant form of gp39. COS cell transfectants expressing gp39
      synergized with either anti-CD20 mAb or PMA to drive strong B cell proliferation
      and alone were able to drive B cells to proliferate weakly. In all cases the B
      cell proliferation induced by gp39-expressing COS cells was reduced to background
      levels by the addition of soluble CD40. Unlike gp39-expressing COS cells,
      recombinant soluble gp39 was not mitogenic alone and required co-stimulation to
      drive B cell proliferation. These results suggest that B cells require a second
      signal besides gp39-CD40 to drive proliferation and that soluble gp39 alone in a
      non-membrane bound form is able to provide co-stimulatory signals to B cells.

PMID- 1385115
TI  - Cytokine effects of CD23 are mediated by an epitope distinct from the IgE binding
      site.
AB  - Human CD23 and its soluble forms (sCD23) display various biological activities,
      in addition to their IgE binding function (IgE/BF). The IgE binding domain was
      recently mapped to residues between Cys163 and Cys282 but its involvement in IgE
      independent, CD23 functions remains unknown. In order to clarify this point, a
      series of N-terminal, C-terminal and internal deletion mutants of CD23 or sCD23
      were expressed in CHO cells and tested for their ability (i) to bind to IgE, (ii)
      to induce colony formation by human myeloid precursor cells, (iii) to promote
      mature T cell marker expression by early prothymocytes, and (iv) to regulate IgE
      synthesis. The present study indicates that cytokine activities require the
      presence of Cys288, while this amino acid is not necessary for IgE/BF. Blocking
      experiments using various conformation-sensitive monoclonal antibodies further
      suggest that active epitope(s) of CD23 in cytokine assays is(are) distinct from
      those involved in IgE/BF.

PMID- 1385116
TI  - Identification of two structurally related proteins involved in proteolytic
      processing of precursors targeted to the chloroplast.
AB  - Two proteins of 145 and 143 kDa were identified in pea which co-purify with a
      chloroplast processing activity that cleaves the precursor for the major light
      harvesting chlorophyll binding protein (preLHCP). Antiserum generated against the
      145/143 kDa doublet recognizes only these two polypeptides in a chloroplast
      soluble extract. In immunodepletion experiments the antiserum removed the
      doublet, and there was a concomitant loss of cleavage of preLHCP as well as of
      precursors for the small subunit of Rubisco and the acyl carrier protein. The 145
      and 143 kDa proteins co-eluted in parallel with the peak of processing activity
      during all fractionation procedures, but they were not detectable as a homo- or
      heterodimeric complex. The 145 and 143 kDa proteins were used separately to
      affinity purify immunoglobulins; each preparation recognized both polypeptides,
      indicating that they are antigenically related. Wheat chloroplasts contain a
      soluble species similar in size to the 145/143 kDa doublet.

PMID- 1385118
TI  - The effect of pedaling frequency on glycogen depletion rates in type I and type
      II quadriceps muscle fibers during submaximal cycling exercise.
AB  - This study was conducted to determine whether the pedaling frequency of cycling
      at a constant metabolic cost contributes to the pattern of fiber-type glycogen
      depletion. On 2 separate days, eight men cycled for 30 min at approximately 85%
      of individual aerobic capacity at pedaling frequencies of either 50 or 100
      rev.min-1. Muscle biopsy samples (vastus lateralis) were taken immediately prior
      to and after exercise. Individual fibers were classified as type I (slow twitch),
      or type II (fast twitch), using a myosin adenosine triphosphatase stain, and
      their glycogen content immediately prior to and after exercise quantified via
      microphotometry of periodic acid-Schiff stain. The 30-min exercise bout resulted
      in a 46% decrease in the mean optical density (D) of type I fibers during the 50
      rev.min-1 condition [0.52 (0.07) to 0.28 (0.04) D units; mean (SEM)] which was
      not different (P > 0.05) from the 35% decrease during the 100 rev.min-1 condition
      [0.48 (0.04) to 0.31 (0.05) D units]. In contrast, the mean D in type II fibers
      decreased 49% during the 50 rev.min-1 condition [0.53 (0.06) to 0.27 (0.04)
      units]. This decrease was greater (P < 0.05) than the 33% decrease observed in
      the 100 rev.min-1 condition [0.48 (0.04) to 0.32 (0.06) units). In conclusion,
      cycling at the same metabolic cost at 50 rather than 100 rev.min-1 results in
      greater type II fiber glycogen depletion. This is attributed to the increased
      muscle force required to meet the higher resistance per cycle at the lower pedal
      frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385117
TI  - GATA-1 but not SCL induces megakaryocytic differentiation in an early myeloid
      line.
AB  - GATA-1, a transcription factor of the 'zinc-finger' family, is required for the
      development of mature erythroid cells and is also highly expressed in the
      megakaryocytic and mast cell lineages. The helix-loop-helix gene SCL (or TAL) is
      expressed in the same three hematopoietic lineages as GATA-1. To explore the role
      of GATA-1 and SCL in hematopoietic differentiation, we introduced a new
      expression vector bearing each gene into the early myeloid cell line 416B, which
      could originally differentiate in vivo along the megakaryocytic and granulocytic
      lineages. Enforced expression of SCL at high levels did not provoke
      differentiation, but GATA-1 induced the appearance of megakaryocytes as assessed
      by morphology, the presence of acetylcholinesterase and a polyploid DNA content.
      Although GATA-1 is thought to stimulate its own transcription in erythrocytes,
      expression of the endogenous gene was not increased in the megakaryocytic lines;
      hence GATA-1 may not be autoregulatory in this lineage. Megakaryocytic
      differentiation was accompanied by a marked decrease in the myeloid surface
      marker Mac-1. The absence of mast cell or erythroid differentiation suggests that
      GATA-1 may not be sufficient to provoke maturation along these lineages or that
      these pathways are impeded in 416B cells. These results demonstrate that a member
      of the GATA gene family can act as an important regulator of megakaryocytic
      differentiation.

PMID- 1385119
TI  - Characterization of the reverse transcriptase of 1731, a Drosophila melanogaster
      retrotransposon.
AB  - The nucleotide sequence of 1731, a retrotransposon cloned from the genome of
      Drosophila melanogaster, reveals a structural similarity with the proviral form
      of the retroviruses including a pol-like gene containing a putative reverse
      transcriptase(RT)-coding sequence. Diverse parts of that sequence were subcloned
      and expressed in Escherichia coli. It has been demonstrated that the expression
      of the RT-like sequence, when translated, gives rise to peptides displaying
      enzyme activity characteristic of a true RT enzyme. In addition, rabbit antisera
      directed against such recombinant proteins allowed us to detect an immunoreactive
      protein of around 110 kDa, which was only present in D. melanogaster cell lines,
      but not in cells derived from Drosophila virilis or Drosophila hydei, whose
      genomes do not bear the 1731 element. This protein is expected to correspond to a
      non-processed pol-gene translated product and cosediments with virus-like
      particles exhibiting RT activity.

PMID- 1385121
TI  - Stable expression of chicken type-VI collagen alpha 1, alpha 2 and alpha 3 cDNAs
      in murine NIH/3T3 cells.
AB  - As a component of an extensive network of microfibrils interwoven with large
      collagen fibers and in close contact with cell surfaces, type VI collagen plays
      an important role in cell-matrix interactions. To investigate the behaviour of
      chicken type VI collagen chains in heterologous host cells as a means to
      understanding the pattern of assembly of this collagen, we transfected murine
      NIH/3T3 cells with cDNAs encoding chicken alpha 1(VI), alpha 2(VI) and alpha
      3(VI) chains. Cell lines that constitutively expressed the individual chains were
      analyzed by metabolic labeling and immunoprecipitation with specific antibodies.
      No self-association was observed for either alpha 1(VI) or alpha 2(VI) chains
      which were secreted as monomeric polypeptides. Furthermore, neither the chicken
      alpha 1(VI) nor alpha 2(VI) chains associated with the endogenous murine chains
      to form chimeric chicken/murine heterotrimers. In contrast, chimeric
      chicken/murine heterotrimers were detected in cell lines transfected with chicken
      alpha 3(VI) cDNA. These chimeric forms appeared to be properly aligned since
      their triple helices were stable to pepsin digestion. In addition, the chimeric
      heterotrimers coassembled and gave rise to disulfide-linked type VI collagen
      molecules.

PMID- 1385120
TI  - Isolation and characterization of alliinase cDNA clones from garlic (Allium
      sativum L.) and related species.
AB  - cDNA libraries constructed from poly(A)-rich RNA isolated from Allium sativum
      (garlic), Allium cepa (onion) and Allium ascalonicum (shallot) were screened for
      cDNA clones encoding the alliinase using colony hybridization. Sequence analysis
      of the alliinase cDNA clones from different Alliaceae species revealed a high
      degree of sequence similarity both at the nucleotide and at the amino acid level.
      Apparently, the alliinases are translated from mRNA species of approximately 2200
      nucleotides. The primary translation products are preproproteins which are
      converted into the mature alliinases following post-translational modifications.
      In the case of the garlic alliinase, the mRNA encodes a 486-amino-acid
      polypeptide with a molecular mass of 55,623 Da. Cleavage of the signal peptide
      (28 amino acids) results in a preprotein which extends 10 amino acids before the
      first amino acid of the mature protein of 51,451 Da. Southern-blot analysis of
      genomic DNA has shown that the alliinases are most probably encoded by a family
      of closely related genes, which is in good agreement with the sequence
      heterogeneity found between different alliinase cDNA clones of one species.

PMID- 1385122
TI  - Tenascin: a modulator of cell growth.
AB  - The large, multidomain extracellular matrix protein tenascin displays a markedly
      restricted tissue distribution during embryogenesis and remains present only in a
      few adult tissues. The protein is reexpressed, however, during wound healing and
      in the stroma of malignant tumours. While a variety of studies have dealt with
      the important role of tenascin in the development of neural and non-neural
      tissues, there is growing evidence that tenascin expression may be associated
      with proliferation of cells lining these tissues. The presence of repeating
      domains in tenascin similar to those in epidermal growth factor prompted us to
      investigate the ability of tenascin to modulate the growth of different cell
      types. Tenascin was actually found to be mitogenic for several cell types. This
      mitogenic activity, however, appears to be associated with a region in the
      fibronectin type III domains. The mitogenic mechanism is clearly distinct from
      pathways used by peptide growth factors such as epidermal growth factor and
      platelet-derived growth factor, which activate the intrinsic tyrosine kinase
      activity of their cell-surface receptors. However, we show that this large
      extracellular matrix molecule is efficiently internalised and may be processed by
      responding cells.

PMID- 1385123
TI  - The major zymogen granule membrane protein GP-2 in the rat pancreas is not
      involved in granule formation.
AB  - The major membrane protein of zymogen granules in the rat pancreas is a
      glycoprotein of 78 kDa (GP-2), which is inserted into the membrane via a glycosyl
      phosphatidylinositol (GPI) anchor. GP-2 occurs in both, a membrane-attached and a
      soluble form. Due to its specific luminal orientation and its quantitative
      contribution to the zymogen granule membrane, GP-2 has been postulated to play an
      important role in sorting of digestive enzymes into the granule and in the
      formation of the granule as a storage organelle. We have tested this hypothesis
      in the rat pancreas under three different functional conditions, where both the
      rates of enzyme/isoenzyme synthesis change drastically, and new zymogen granules
      form at a high rate: a) during prolonged hormonal stimulation of the adult rat
      pancreas, b) during the differentiation of AR4-2J cells induced by dexamethasone
      in vitro, and c) during embryonic development and early postnatal life, when gene
      expression is modulated due to the differentiation program. Both, GP-2 mRNA
      levels and the rate of GP-2 biosynthesis were quantitated and compared to the
      immunohistochemical localization of this protein in tissue sections. Under all
      three functional conditions, significant changes could be demonstrated at the
      level of digestive enzyme gene expression, but no concomitant modulation of GP-2
      expression was observed. GP-2 mRNA is absent from the embryonic pancreas and for
      the first time is expressed after birth with a significant increase during the
      period of weaning. Furthermore, GP-2 mRNA and protein levels are not modulated by
      hormonal stimulation, either in the adult pancreas or in AR4-2J cells in culture.
      Therefore, we conclude that GP-2, in spite of its quantitative contribution to
      the zymogen granule membrane, is not involved in enzyme protein sorting or
      granule formation. Alternative functions for GP-2 are discussed.

PMID- 1385124
TI  - Characteristics of pancreatic exocrine secretion produced by venom from the
      Brazilian scorpion, Tityus serrulatus.
AB  - The influence of venom (TSV) from the Brazilian scorpion, Tityus serrulatus, on
      exocrine pancreatic secretion was studied in relation to known cholinergic and
      peptidergic secretagogue activity. Pulse-labeling followed by chase incubation in
      the presence of secretagogues and various pharmacological agents revealed unique
      physiological characteristics of TSV in guinea pig pancreatic lobules. Exocytotic
      discharge of newly synthesized 3H-labeled proteins during a 3-h chase incubation
      showed a marked increase over basal discharge levels using logarithmic TSV doses
      of 0.10 to 100 micrograms/ml. This stimulation was comparable to maximal values
      elicited by carbachol, cholecystokinin-octapeptide (CCK-8) or caerulein and
      discharge kinetics were similar. TSV-mediated secretion was ATP and calcium
      dependent and partially inhibited by atropine. Only tetrodotoxin completely
      blocked TSV stimulation of newly synthesized protein discharge. Both botulinum
      toxin and curare had no effect on venom stimulation, indicating that TSV
      interaction with exocrine pancreatic cells occurs postsynaptically. Verapamil, a
      calcium channel antagonist, produced a moderate inhibition of TSV stimulation.
      When antagonists to the cholecystokinin (CCK) receptor were incubated with TSV,
      no change in secretory activity occurred. Therefore, TSV does not bind to CCK
      receptors and probably operates through its own receptor which may be an ion
      channel. Additionally, morphological studies in vitro revealed a high level of
      pancreatic secretory activity as evidenced by dense secretory acinar luminal
      content, reduction in zymogen granule (ZG) population, and development of
      exocytotic images.

PMID- 1385126
TI  - Serum osteocalcin in monitoring bone metastases in advanced prostatic cancer.
AB  - Osteocalcin, a K-dependent vitamin protein, was studied in a group of advanced
      prostatic carcinoma patients to test the usefulness of this marker for diagnosing
      bone metastases. Osteocalcin levels were above the norm in 22 out of 27 patients
      with bone metastases, although high levels were not observed in patients without
      bone metastases. High sensitivity and specificity levels of serum osteocalcin
      appear to be strongly correlated to metastatic bone involvement and disease
      relapse after hormone treatment. Although these results must be confirmed on a
      larger series of patients, this protein appears to be a useful biological marker
      in prostatic cancer.

PMID- 1385125
TI  - Antigenic determinants of T lymphocyte alpha beta receptor and other leukocyte
      surface proteins as differential markers of skeletal muscle regeneration:
      detection of spatially and timely restricted patterns by MAM microscopy.
AB  - Different stages of human muscle regeneration have been identified by multiple
      antigen-mapping (MAM) microscopy at the level of a novel marker system. This
      immunofluorescence method allows the selective imaging of numerous antigen
      signals from cells or tissue sections. It is shown that 2 monoclonal antibodies
      (mAbs) against the common region of the alpha beta T lymphocyte antigen receptor
      (alpha beta and alpha TCR chains) and 3 mAbs against the leukocyte surface
      antigens Leu8, OKM5 and Leu19 recognize regenerating muscle cells at different
      time points of regeneration in human muscle sections. Paradoxically, these
      epitopes are not expressed by T lymphocytes or other mononuclear leukocytes
      invading regenerating muscle. Hence, presence of the corresponding antigens in
      muscle fibers may exclude their expression by muscle-invasive immune cells
      suggesting a function in muscle-specific cell-to-cell recognition. Simultaneous
      localization of these epitopes in Duchenne dystrophy reveals 10 different
      phenotypes of regenerating and normal infantile muscle cells due to different
      developmental stages during the myocyte differentiation. In adult muscle
      (mitochondrial myopathy) segmental muscle fiber necrosis is accompanied by high
      concentration of alpha beta/alpha TCR epitopes in the intact fiber ends, which
      are the target sites of myogenesis. The same sites are invaded by OKM5+
      endomysial capillary sprouts that terminate at the tip of the alpha beta/alpha
      TCR reactive fiber ends. These hitherto unrecognized initial events of segmental
      muscle regeneration seem to be followed by fragmentation of the invasive
      capillaries into single endothelial cells, which then switch from the OKM5+ Leu19
      through the OKM5+ Leu19+ to the OKM5- Leu19+ phenotype. This cell type exhibits
      the typical features of Leu19+ myogenic stem cells described earlier. The
      findings may give rise to a concept of muscle repair, in which the alpha
      beta/alpha TCR-related antigen, concentrated in fiber stumps, might provide
      positional information for invading endothelial cells. These cells appear to be a
      source of myogenic stem cells for regeneration.

PMID- 1385127
TI  - Advanced prostate cancer follow-up with prostate-specific antigen, prostatic acid
      phosphatase, osteocalcin and bone isoenzyme of alkaline phosphatase.
AB  - We report our experience in the follow-up of 63 patients with advanced prostate
      adenocarcinoma. We used prostate-specific antigen and prostatic acid phosphatase
      in 27 patients; in 36 patients we evaluated osteocalcin and bone isoenzyme of
      alkaline phosphatase, two markers of bone metabolism which seem to be good
      markers in the follow-up of patients with bone metastases.

PMID- 1385128
TI  - Relationship between prostatic acid phosphatase and prostate-specific antigen
      serum levels and prostatic volume in benign prostate hyperplasia. Pitfall on
      tumor markers assessment in primary prostatic cancer?
AB  - Serum levels of prostatic acid phosphatase (PAP) and prostate-specific antigen
      (PSA) were measured in 78 patients with benign prostate hyperplasia and compared
      with both the gland weight and the glandular component of prostatic tissue. Both
      PAP and PSA were significantly higher where prostate was heavier; however, we
      could not find a consistent factor which could correlate weight increase to
      marker levels. PSA tended to be higher when glandular component was more
      expressed. From the present findings we conclude that in patients with prostate
      cancer, PAP and PSA serum levels should be investigated considering also the
      benign components of prostate gland.

PMID- 1385129
TI  - Seasonal variation of prostatic acid phosphate and prostate-specific antigen in
      patients without prostatic malignancy.
AB  - The seasonal pattern of prostatic acid phosphatase (PAP) and prostate specific
      antigen (PSA) in nonmalignant males was investigated. Serum levels were measured
      in 1,540 men during a 3-year period with radioimmunoassay methods using
      monoclonal antibody techniques. All of the tested individuals were free of
      prostatic malignancy. During each of the 3 years, PAP ans PSA showed a rise,
      especially in spring. The mean PSA level in spring showed a statistically
      important difference when compared with winter, fall and summer mean levels (p
      less than 0.05). However, no significant difference of PAP levels was estimated
      seasonally in the 3 years, which shows that an important marker of prostatic
      cancer can vary with seasons.

PMID- 1385130
TI  - A new marker for early detection and indicator of progression of cancer of the
      bladder. Preliminary results with Ag-NOR index in 38 cases of superficial bladder
      cancer.
AB  - The multiform biology of superficial bladder tumors, both morphologically and
      evolutively, and the lack of reliable predictors of progression have led the
      authors to study the Ag-NOR proteins as a new marker of these tumors. It is well
      known that particularly the low-grade superficial tumors frequently relapse on
      the same histologic and proliferative module. Their potential of progression is
      probably present at the time of the first manifestation of the disease or it can
      show itself along the relapsing evolution with classic modifications translating
      the cellular dedifferentiation. The NOR index, set up by the authors, has several
      advantages: firstly, it corresponds to a functional value of normal and
      neoplastic cells; secondly, it can be used also with paraffin blocks. Another
      advantage is the semiautomatic lecture, reproducible also in the urinary
      cytology, mainly of low-grade tumors, reducing the number of false-negatives. The
      conclusion of the study of 38 cases of superficial bladder cancer has induced the
      authors to believe that an increased NOR index is a reliable 'marker' of their
      progression. Therefore, the authors suggest the use of the NOR activity for the
      surveillance of the urothelial disease and for a more logical therapeutic
      strategy.

PMID- 1385131
TI  - Current status of tumor markers in testicular cancer. A practical review.
AB  - Detection of serum and cellular AFP and hCG has made a significant contribution
      in understanding and management of testicular cancer. It is essential to remember
      the following events in utilizing these markers: (1) Histologic diagnosis of
      seminoma, but AFP is elevated. There is usually an element of choriocarcinoma.
      (2) Histologic diagnosis of seminoma and highly elevated hCG greater than 100
      ng/ml has usually an element of choriocarcinoma. (3) Histologic diagnosis of
      choriocarcinoma with an elevated serum AFP. There is usually an element of
      embryonal carcinoma. (4) Pathologic stage I nonseminomatous testicular cancer
      with elevated serum markers is either stage II or stage III. (5) In a recent
      study of 23 patients undergoing resection of residual nonseminomatous testicular
      cancer after intensive chemotherapy, 21 had either teratoma in primary tumor or
      bulky metastatic disease. The markers were normalized after chemotherapy and
      prior to resection. (6) Although normalization of these markers after
      chemotherapy indicates effective therapeutic response, one should look of
      residual tumor utilizing radiologic investigations.

PMID- 1385133
TI  - Evaluation of hematochemical parameters and renal echography after ESWL.
AB  - Evaluation of hematochemical parameters and renal echography after ESWL treatment
      with Tripter X1 was done on the first 95 patients treated and for whom we had a
      longer than 3-month follow-up. Creatinine phosphokinase values showed an increase
      in 24 patients. 12 patients demonstrated an increase in amylasemia. Echographic
      checks performed the day after treatment revealed the presence of perirenal
      lesions in 3 cases. As far as amylasemia is concerned, only 1 patient was treated
      with aprotinin. One of the patients who developed perirenal hematoma had
      hypertension; another was following an antiaggregant therapy that was temporarily
      suspended.

PMID- 1385132
TI  - Beta-human chorionic gonadotropin and alpha-fetoprotein in central and peripheral
      venous blood of patients with testicular tumors.
AB  - From January 1989 to June 1991, 18 patients ranging in age from 19 to 41 (mean
      34) years with testicular tumor were examined. 14 patients had seminoma (11
      typical and 3 spermatocytic) and 4 patients had a mixed form (2 seminoma +
      embryonal tumor and 2 seminoma + teratocarcinoma). Serum levels of beta-human
      chorionic gonadotropin and alpha-fetoprotein from peripheral venous blood and
      from spermatic venous vessel were evaluated in every patient. All patients with
      seminoma and in a patient with mixed tumor (seminoma + embryonal tumor) the
      markers were regular. The increase of the markers was found in the peripheral and
      in spermatic blood of 3 patients (2 seminoma + embryonal carcinoma and 1 seminoma
      + teratocarcinoma). For these reasons the values of spermatic vessels are an
      important confirmation of the level of peripheral markers.

PMID- 1385134
TI  - Tissue markers in the diagnosis and prognosis of prostatic carcinoma.
AB  - Prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), and beta
      microseminoprotein are organ-specific markers. Also Leu-7 may be regarded as an
      organ-specific marker. The main utilization of PAP and PSA immunostaining is to
      establish the prostatic origin of a carcinoma. Changes of PAP and PSA
      immunoreactivity may be correlated with histologic grade of prostatic carcinoma.
      Keratin expression assessment is useful to identify prostatic basal cells or
      epithelial secretory cells. Neuroendocrine marker reactivity in prostatic
      carcinoma seems to be related with increasing histologic grade and tumor
      progression.

PMID- 1385135
TI  - Correlation between serum values of prostatic acid phosphatase and morphometric
      analysis in the cytologic diagnosis of prostatic carcinoma.
AB  - We studied 78 men with suspicion of prostatic carcinoma, who underwent
      transrectal aspiration biopsy, diagnosing 46 adenocarcinoma, 13 chronic
      prostatitis and 19 benign prostatic hyperplasia. Moreover, we determined
      prostatic acid phosphatase (PAP) by enzyme immunoanalysis, resulting in 9/78
      false-positives and 18/78 false-negatives. Also, we carried out a morphometric
      analysis of the cytologic samples which showed good correlation with the
      cytologic diagnosis except in the moderately differentiated carcinomas. We found
      a good correlation between PAP values, cytologic diagnosis and nuclear size as
      well as the percentage of the binucleolated cells.

PMID- 1385136
TI  - New ultrasensitive assay development by using monoclonal antibodies for detecting
      prostate-specific antigen.
AB  - The Serono Maia Clone prostatic-specific antigen (PSA) kit incorporates an
      immunoradiometric assay for the measurement of PSA in the serum. The method can
      be used over a range of 0-100 ng/ml without dilution. Standard concentrations are
      0, 0.4, 1, 5, 20, and 100 ng/ml. Up to date, 373 normal men, 89 normal women, 117
      prostatic carcinoma, 98 other carcinoma, and 85 benign prostatic hypertrophy have
      been tested. The aim of this study is to evaluate the sensitivity and specificity
      of a new immunoassay method for the determination of PSA, that could be able to
      evaluate low levels of PSA, resulted undetectable with other methods. This
      ability could be useful in patients treated with hormone-suppressive therapy or
      after radical prostatectomy. We have collected all low values present in samples
      examined. With the Serono Maia Clone PSA kit only 26.7% of these have been
      evaluated as 'out' values as opposed to 46.5% with the Hybritech kit.

PMID- 1385137
TI  - Changes in prostate-specific antigen and prostatic acid phosphatase concentration
      following prostatic examination in benign prostatic hypertrophy and prostate
      cancer patients.
AB  - The authors measured serum prostate-specific antigen (PSA) and prostatic acid
      phosphatase concentration in histologically positive prostate hyperplastic and
      carcinomatous patients before, and 30-60 min and 24 h after prostate manipulation
      (rectal digital examination, cystoscopy and perineal punch biopsy). After rectal
      examination, PSA, and after other interventions, both markers changed
      significantly, although in different points of time and to a different extent.
      The authors call the attention to the importance of the point of time of the
      examination. Examination following prostate manipulation may result in wrong
      diagnosis or in erroneous therapeutic consequences in the follow-up period.

PMID- 1385138
TI  - Comparison between digital rectal examination, prostate-specific antigen and
      transrectal ultrasound in symptomatic patients. Results on 141 cases.
AB  - In this study we proposed to verify sensitivity and specificity of prostate
      specific antigen (PSA), digital rectal examination (DRE) and transrectal
      ultrasound (TRUS) in patients who referred at our institution for prostatic
      complaints. 141 patients, ages ranging between 55 and 86 years (mean 67.5),
      underwent DRE, blood PSA, TRUS and ultrasonically guided biopsy of the prostate.
      The comparison of the results obtained with the different diagnostic tools
      allowed us to draw a diagnostic algorithm for prostate cancer in symptomatic
      patients.

PMID- 1385139
TI  - Prognostic significance of prostate-specific antigen in endocrine treatment for
      prostatic carcinoma.
AB  - We have studied the prognostic significance of prostate-specific antigen (PSA),
      monitored monthly, in 24 patients with prostatic cancer (5 D1, 19 D2) on
      endocrine therapy. The pretreatment levels of PSA were high in all patients (mean
      value 41 ng/ml). It was found that PSA levels at the end of the first and sixth
      months of treatment were reliable prognostic indicators. At the first month
      evaluation PSA had decreased more than 50% from the initial values in the 16
      patients with stable disease, while it had decreased less than 50% in those with
      progressing disease. At the end of 6 months, patients with stable disease had PSA
      levels within the normal range, while 8 of the patients who had progressing
      disease had levels higher than 10 ng/ml. Respectively 6 and 2 patients had also
      had increases in PSA levels at 3 and 6 months before scintigraphic demonstration
      of increased bone metastases.

PMID- 1385140
TI  - Preoperative and postoperative evaluation of prostate-specific antigen in
      localized prostatic cancer treated by radical prostatectomy.
AB  - Preoperative prostate-specific antigen (PSA) values were determined in 73
      patients with clinically localized prostatic cancer and candidates for a radical
      procedure. Correlation of preoperative PSA with a final pathological stage was
      attempted. Only in 44.8% of our 22 patients with organ-confined disease was the
      PSA value within the normal range; in 17.3% of cases PSA values were higher than
      20 ng/ml. 18.2% of the patients with locally advanced disease showed normal PSA
      values, while 45.5% had concentrations above 20 ng/ml. In the case of lymph node
      involvement, PSA values were normal in 22.7% of the cases. Our data indicate that
      no strict relationship can be suggested between PSA and the final pathological
      stage and grading of the tumor in patients who underwent radical prostatectomy.

PMID- 1385142
TI  - Prostate-specific antigen and prostate acid phosphatase in the detection of early
      prostate cancer and the prediction of regional lymph node metastases.
AB  - Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase
      (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical
      prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all
      tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA
      determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the
      patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a
      stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed,
      however, by digital rectal examination. This indicates that PSA determination
      cannot replace digital rectal examination as a screening method for prostate
      cancer. In this study, it was possible neither by PSA nor by PAP to define a
      practicable cutoff level for patients with and without lymph node metastases. A
      clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible
      by either PSA or PAP alone.

PMID- 1385141
TI  - Influence of prostatic disease and prostatic manipulations on the concentration
      of prostate-specific antigen.
AB  - We examined the influence of different factors [benign prostatic hyperplasia
      (BPH), prostatic carcinoma (PCA), organ volume, weight of resected tissue,
      transurethral catheter] on the serum prostate-specific antigen (PSA) levels in
      253 patients with BPH (n = 138; 54%) and PCA (n = 115; 46%). Only in 57.2% of the
      BPH patients, PSA values were < 4 ng/ml, in 74.6% < 7 ng/ml. In 108 patients with
      BPH, a transurethral prostatectomy was performed. PSA values correlated
      significantly with the sonographically determined prostatic volumes and less
      precisely with the weight of the resected tissue. The PSA concentration per
      milliliter of prostatic volume was 0.12 ng/ml, per gram of resected tissue it was
      0.21 ng/ml. An incidental PCA was found in 12/108 patients (11%). The PSA values
      were identical with those of the total collective in regard to volume and tissue
      weight. In 11 patients, we examined possible alterations of the PSA values before
      and until 24 h after prostatic massage. Only insignificant alterations were seen,
      a massive increase was not found in any patient. Searching for an absolutely
      valid 'normal value' appears hardly appropriate. However, the usefulness of PSA
      is increased when the sonographically determined prostatic volume is included. A
      rectal examination of the prostate has no influence on the PSA value.

PMID- 1385144
TI  - Transurethral radiofrequency heating or thermotherapy for benign prostatic
      hypertrophy: a prospective trial on 65 consecutive cases.
AB  - 65 consecutive cases with symptomatic benign prostate hypertrophy were treated
      with transurethral radiowave thermotherapy (TURF) using the Thermex-II at a
      temperature of 44.5 degrees C. We report uroflowmetry and symptom scores after a
      follow-up of 6 months. The mean age was 63 years, the mean maximal flow (Qmax)
      was 8.3 ml/s, mean voided volume was 195.6 ml, mean residual urine was 60.7 ml
      and the mean Madsen symptom score 9.7. Values at baseline and at 1, 3 and 6
      months after TURF are discussed. The mean subjective symptom score dropped to 6.3
      (p < 0.01). In the entire group, the objective measure scores (OMS) did not
      change significantly. However the OMS improved significantly in a subgroup with a
      Qmax < 10.0 ml/s. The Madsen symptom score improved in 70% of the cases after 6
      months.

PMID- 1385143
TI  - Prediction of pelvic lymph node metastases by a prostate-specific antigen and
      prostatic acid phosphatase in clinical T3/T4M0 prostatic cancer.
AB  - Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were
      determined in the serum of 69 patients with clinical T3/T4M0 prostatic cancer
      before staging lymphadenectomy. In principle, high-dose radiotherapy was given
      only to patients of pathological N0 category. Seventeen patients had a
      prelymphadenectomy PSA level below the normal upper reference limit (10
      micrograms/l) and only 3 of them had pelvic lymph node metastases. Fifteen of 52
      patients with a preoperative PSA level > or = 10 micrograms/l were of N0
      category. Only 8 of the 41 evaluable patients had PAP values above the normal
      range, and 6 of these 8 patients had pelvic lymph node metastases. Preoperative
      PSA values, but not preoperative PAP levels, assist the clinician in predicting
      regional lymph node metastases in patients with clinical T3/T4M0 prostatic
      cancer. Two-thirds of the patients with T3/T4 tumours and PSA values between 10
      and 50 micrograms/l have regional lymph node metastases. About 80% of the
      patients with PSA levels < 10 micrograms/l belong to the N0 category. About 75%
      of the patients with PSA > 50 micrograms/l have N+ disease. Taking into account
      the individual preoperative PSA values, the indication for preradiotherapy
      staging lymphadenectomy should be balanced between the chance of demonstrating N+
      disease, the expected postoperative morbidity and the benefit for the patient
      found to be of N0 category.

PMID- 1385145
TI  - The 'female prostate': location, morphology, immunohistochemical characteristics
      and significance.
AB  - Using immunostaining for prostate-specific antigen (PSA) and prostatic acid
      phosphatase (PAP), we can demonstrate prostate-analogous periurethral glands (the
      'female prostate') in 66.7% of 33 cases. Histomorphologically, these glands
      resemble strongly the male prostate glands before puberty. They remain immature
      throughout life from the fetal period up to advanced age obviously because of a
      lack of an androgenic stimulus. The glands have long ducts leading into the
      urethra. A proper stroma component is missing. The immunohistochemical behavior
      of these glands also corresponds widely to that of the male prostate glands
      before puberty. No indications can be found for a proper biological function.

PMID- 1385146
TI  - Transrectal hyperthermia-induced histological and ultrastructural changes of
      human benign prostatic hyperplasia tissue.
AB  - This prospective study evaluated the tissutal, cellular and intracellular effects
      of transrectal microwave hyperthermia on human benign prostatic hyperplasia.
      Forty-eight patients with benign prostatic hyperplasia underwent ten 60-min-long
      sessions of transrectal hyperthermia with an intraprostatic calculated
      temperature of 42 +/- 0.5 degrees C. Ultrasound-guided transperineal biopsies of
      the prostate were taken before and 1 month after completion of treatment.
      Postoperatively, morphometric analysis of bioptic specimens showed a
      statistically significant (p < 0.01) increase in the number of intraprostatic
      arterioles and capillary-like vessels. Diffused inflammatory infiltrates were
      also noted. Postoperative integrity of intracellular organelles and cellular
      membranes was evidenced by transmission electron microscopy. Our regimen of
      transrectal prostatic hyperthermia did not cause any irreversible histological or
      ultrastructural damage to the prostatic tissue. Hyperthermia-induced increase in
      blood flow could enhance drug delivery to the prostate gland.

PMID- 1385147
TI  - Patient recruitment to and cost of a prospective trial of medical treatment for
      benign prostatic hyperplasia.
AB  - 409 consecutive patients, referred by general practitioners for assumed benign
      prostatic hyperplasia (BPH), were evaluated for inclusion into a hormone therapy
      trial for BPH. 97 patients were excluded initially. Upon examination of the 312
      remaining patients, 221 were found to be ineligible for various reasons and 11
      refused to participate. Other patients were excluded after a second, more
      extensive examination and 5 patients withdrew during the trial. We are now left
      with 66 patients (16.1% of the patients initially referred), of which
      approximately 33 are receiving placebo treatment. The financial costs for the
      hospital to carry out a drug trial with approximately 65 evaluable patients is
      estimated to exceed 40,000 pounds.

PMID- 1385148
TI  - Mack-Forster Award 1992.

PMID- 1385149
TI  - 1992 Mack Forster Award Lecture. Review. Regulation of angiogenesis in vitro.

PMID- 1385150
TI  - Role of hepatitis C virus infection in German patients with fulminant and
      subacute hepatic failure.
AB  - To investigate the possible role of hepatitis C virus (HCV) in fulminant and
      subacute liver failure, we tested serum and liver of 13 patients undergoing
      orthotopic liver transplantation for the presence of HCV RNA. HCV RNA was
      detected in specimens from two out of eight patients negative for all viral
      markers with suspected hepatitis non-A, non-B infection and in one out of four
      patients with hepatitis B virus infection. Only in this patient replication of
      HCV could be demonstrated. We conclude, that fulminant and subacute hepatic
      failure is induced by hepatitis C virus only in few patients with hepatitis non
      A, non-B.

PMID- 1385151
TI  - Structural and functional epitopes of the human adhesion receptor CD58 (LFA-3).
AB  - CD58 (LFA-3), a heavily glycosylated protein of 40-70 kDa, is expressed on a
      broad range of hematopoietic and non-hematopoietic cells. It serves as a
      physiological ligand of the CD2 receptor, present on T cells and natural killer
      cells, and plays, thus, an important role in lymphocyte adhesion and T cell
      activation through CD2. Whereas several epitopes and their respective function
      are known for CD2, a similarly detailed characterization of CD58 is still
      lacking. We raised a panel of novel murine monoclonal antibodies (mAb) against
      recombinant human CD58 and describe here the identification of six structurally
      and/or functionally distinct epitopes on the CD58 molecule. All epitopes were
      found to be present in equal numbers on a wide range of CD58+ cells, none of them
      being differentially up-regulated following cell activation or malignant
      transformation. Two of these epitopes represent functionally relevant sites,
      involved in binding of CD58 to CD2 and T cell activation via CD2. One further
      epitope appears to be selectively involved in CD58-mediated activation, whereas
      the other three displayed no functional effects. The new mAb allow for the first
      time the detection of CD58 in enzyme-linked immunosorbent assays and
      immunofluorescence while bound to its receptor CD2 in human serum or on freshly
      isolated blood cells. Finally, one mAb was found to specifically cross-react with
      T11TS, the equivalent of CD58 in sheep.

PMID- 1385152
TI  - Proliferation and differentiation of human CD5+ and CD5- B cell subsets activated
      through their antigen receptors or CD40 antigens.
AB  - The pan-T cell antigen CD5 has been shown to delineate two different mouse B cell
      subsets, originating from distinct progenitors. In man, on average, 30% of the
      tonsillar B cell pool expresses this antigen. In the present report, a detailed
      comparison of the CD5+ and CD5- B cell response to cytokines, following
      activation via surface immunoglobulins (sIg) or CD40 antigen, was undertaken.
      CD5+ B cells were positively selected by panning or by sorting from tonsils. Two
      color immunofluorescence analysis performed on tonsillar B cell populations
      showed that CD5+ B cells displayed most of the phenotypic features of mantle zone
      B cells. CD5+ B cells could be stimulated for DNA synthesis by mitogenic
      concentrations of Staphylococcus aureus, Cowan I strain (SAC), insolubilized anti
      IgM antibodies, immobilized anti-CD40 antibodies and phorbol 12-myristate 13
      acetate (PMA). The growth-response of small dense CD5- B cells to these T cell
      independent mitogens was comparable to that of CD5+ B cells, whereas the low
      density, in vivo-activated, CD5- B cells were only marginally stimulated by Ig
      cross-linking agents and PMA. Following ligation of sIg, both B cell subsets
      proliferated essentially in response to interleukin (IL)-2 and IL-4. When used in
      co-stimulation with immobilized anti-CD40 antibodies, IL-4 promoted growth of
      CD5+ and CD5- B cells, whereas IL-2 displayed only moderate stimulatory effects.
      CD5+ and CD5- B cells differentiated into Ig-secreting cells when they were co
      cultured with SAC or cross-linked anti-CD40 antibodies and IL-2. However, IgM
      constituted the major component of the Ig response of CD5+ B cells, whereas high
      levels of IgG were secreted by CD5- B cells.

PMID- 1385153
TI  - Co-stimulation of murine CD4 T cell growth: cooperation between B7 and heat
      stable antigen.
AB  - The B cell activation antigen B7/BB1 has been shown to co-stimulate growth of
      human T cells by binding the T cell molecule CD28. In mice, the heat-stable
      antigen (HSA) has also been shown to act as a co-stimulator for T cell growth. In
      this study, we have evaluated the contributions of B7 and HSA to the co
      stimulatory activity of antigen-presenting cells (APC). Mouse B7 provides co
      stimulatory activity for murine CD4 T cells in anti-CD3-induced proliferation.
      Human CTLA4Ig, a chimeric molecule comprising the extracellular region of CTLA-4
      fused to an immunoglobulin C gamma fragment, binds to murine B7. We, therefore,
      use human CTLA4Ig and the hamster anti-HSA monoclonal antibody 20C9 to analyze
      the relative contributions of B7 and HSA to the co-stimulatory activity of murine
      spleen APC. Our data reveal that both murine B7 and HSA are expressed by
      dendritic cells and by low-density spleen B cells. Either CTLA4Ig alone or anti
      HSA alone inhibited CD4 T cell proliferation to anti-CD3 by > 90%, while CTLA4Ig
      and anti-HSA together were far more efficient in inhibiting clonal expansion of
      CD4 T cells. These results demonstrate that functionally defined co-stimulation
      involves at least B7 and HSA and suggest that signals delivered by B7 and HSA
      synergize in promoting T cell growth.

PMID- 1385154
TI  - Integrins and other adhesion molecules on lymphocytes from synovial fluid and
      peripheral blood of rheumatoid arthritis patients.
AB  - Cell and matrix adhesion of lymphocytes participates in homing, migration and
      accumulation of these cells in inflamed tissues as well as in the generation of
      immune and inflammatory responses. In inflamed joints of rheumatoid arthritis
      (RA) patients, lymphocytes accumulate in the synovial membrane and the synovial
      fluid. In the present study we have analyzed the expression of integrins and
      other adhesion molecules in synovial fluid lymphocytes (RA-SFL) and paired
      peripheral blood lymphocytes (RA-PBL) from 21 RA patients by immunofluorescence
      flow cytometry. We have also investigated the expression of these adhesion
      molecules on peripheral blood lymphocytes obtained from 13 sex- and age-matched
      healthy controls (CO-PBL). RA-SFL, which consisted mostly of T cells, showed
      higher expression of the integrin subunits beta 1 (CD29), VLA-1 alpha, -3 alpha, 
      4 alpha, -5 alpha and -6 alpha when compared to RA-PBL. In turn, RA-PBL showed
      lower expression of these molecules than CO-PBL. The expression of the
      immunoglobulin-related molecules CD2, CD54 (ICAM-1) and CD58 (LFA-3) was higher
      on RA-SFL when compared to RA-PBL or CO-PBL, and similar results were obtained
      with the beta 2 integrin subunits CD11a and CD18. In contrast, L-selectin (LECAM
      1) and ICAM-2 were expressed at much lower levels on RA-SFL than on RA-PBL or CO
      PBL. CD44, a receptor for hyaluronic acid and collagen, was expressed by most RA
      SFL, RA-PBL and CO-PBL cells but at higher density on RA-SFL. The results
      indicate that RA-SFL express a distinct array of adhesion molecules, similar to
      the one of memory T lymphocytes. This characteristic phenotype may contribute to
      the lymphocytic infiltration of the synovium and to the pathogenesis of RA.

PMID- 1385155
TI  - Enhancement of CD3-induced activation of human intestinal intraepithelial
      lymphocytes by stimulation of the beta 7-containing integrin defined by HML-1
      monoclonal antibody.
AB  - Intraepithelial lymphocytes (IEL) form a large population of T cells in close
      contact with the intestinal lumen and differ from lymphocytes in other lymphoid
      compartments by their predominant CD8+ phenotype and the strong expression of the
      recently characterized beta 7-containing integrin defined by the monoclonal
      antibody (mAb) HML-1. The aim of the present in vitro study was to investigate
      the possible role of the integrin defined by HML-1 in the activation of human IEL
      via the CD3-T cell receptor (TcR) pathway. The proliferative response of IEL to
      optimal concentrations of immobilized OKT3 was found to be similar to that of
      peripheral blood lymphocytes enriched in CD8+ cells. When co-immobilized with
      suboptimal concentrations of OKT3, antibodies directed against CD11a, CD29 and
      the beta 7-containing integrin defined by HML-1 exerted a strong synergistic
      effect on the proliferative response and on the expression of CD25 and CD71
      antigens by human IEL. These data indicate that the CD3-TcR pathway is functional
      in human IEL and contrast with previous observations suggesting that the CD3-TcR
      pathway was difficult to elicit in human IEL. Furthermore, the present data show
      that the immune response of human IEL can be modulated via interactions between
      integrins expressed by IEL and their respective ligands in the mucosa and suggest
      that IEL's activation may depend on the level of expression of integrin ligands
      in the epithelium, particularly of the expression of the as yet unknown ligand
      for the IEL-specific integrin defined by HML-1.

PMID- 1385156
TI  - CD59 molecule: a second ligand for CD2 in T cell adhesion.
AB  - The T cell surface molecule CD2 forms, with its counter-receptor CD58 (LFA-3), a
      powerful adhesion/activation pathway. There is some evidence that CD2 might bind
      more than a single ligand. Chinese hamster ovary cells (CHO) expressing human
      CD59 after cDNA transfection (CD59+CHO) form rosettes with human T cells; these
      rosettes are inhibited in a dose-dependent fashion by the CD59 monoclonal
      antibody (mAb) H19 and by the CD2 mAb O275 known to block natural rosettes, but
      not by the CD2R mAb D66, a poor rosette blocker. CD2+CHO transfectants form
      rosettes with human erythrocytes; these rosettes are inhibited by the CD59 mAb
      H19 in addition to CD2 mAb O275 and CD58 mAb; murine thymoma cells expressing
      human CD2 form rosettes with CD59+CHO cells that again are blocked by CD59 H19
      and by CD2 O275 mAb. In a marked contrast with H19, two others CD59 mAb, YTH 53.1
      and MEM 43, which react with a different epitope on CD59, led to a 50%-70%
      increase of the number of cells forming rosettes. In addition to rosette
      experiments, the binding of 125I-labeled CD59 molecules to CD2+CHO cells was
      specifically inhibited by unlabeled CD59 molecule and CD2 mAb. Furthermore, the
      binding of CD59 molecules to resting T cells induced expression of CD2R epitopes.
      These results directly show that CD2 binds CD59 and that subtle molecular changes
      occur upon binding.

PMID- 1385157
TI  - Use of Torpedo-mouse hybrid acetylcholine receptors reveals immunodominance of
      the alpha subunit in myasthenia gravis antisera.
AB  - The nicotinic acetylcholine receptor (AChR), a pentameric complex of alpha 2 beta
      gamma delta subunits, is the autoantigen in the human autoimmune disease
      myasthenia gravis (MG). Anti-AChR antibodies are found in approximately 90% of MG
      patients and using indirect methods (competitive binding to solubilized AChR),
      peptides, or synthetic peptides, the majority of these antibodies have been shown
      to bind to the AChR alpha subunit. In order to determine directly the AChR
      subunit specificities of MG antibodies, we employed as antigens a novel set of
      hybrid AChR composed of species cross-reacting and non-cross-reacting subunits
      stably expressed in fibroblasts. Sequence similarities of homologous subunits
      among species can vary widely, with mammalian subunits having 87%-96% identity
      and Torpedo-mammalian subunits having 54%-80% identity. These findings are
      reflected in antigenic specificities, with human anti-AChR antisera frequently
      recognizing mouse AChR but rarely recognizing Torpedo. By establishing separate
      cell lines stably expressing all-Torpedo, all-mouse, and different combinations
      of Torpedo and mouse subunits, we were able to provide the first direct evidence
      of a predominant anti-alpha subunit specificity in MG antisera. Functional hybrid
      AChR stably expressed in an intact cell membrane provide us with a system that
      best mimics the in vivo environment of the MG antibody in a binding assay. Such a
      system allows us to investigate a perplexing observation in the field: a poor
      correlation between the patient's clinical status and antibody titer. Those
      antibodies which can interfere with AChR function, such as ones with the ability
      to cross-link AChR and induce their accelerated internalization and degradation
      (antigenic modulation) might represent a subpopulation of MG antibodies important
      in disease induction or maintenance. In this report, we demonstrate that wild
      type and hybrid AChR expressed in fibroblasts can be antigenically modulated by
      intermolecular cross-linking antibodies as AChR are in native muscle cells.
      Because we can monitor dynamic interactions between AChR and MG antibodies, this
      system may allow us to define crucial pathogenic epitopes in MG by expressing
      hybrid, chimeric, and mutant AChR.

PMID- 1385158
TI  - Evidence for an association between the T cell receptor/CD3 antigen complex and
      the CD5 antigen in human T lymphocytes.
AB  - In this work we report that CD5, a T cell accessory activation antigen and
      receptor for the B cell surface protein CD72, is associated with the T cell
      antigen receptor (TcR)/CD3 complex in human T lymphocytes. In vitro
      phosphorylation of either CD3 or CD5 immunoprecipitates prepared from CD3
      stimulated Jurkat and peripheral blood T cells in the presence of the detergent
      polyoxyethelene 10 oleyl ether (Brij96) showed, unexpectedly, an identical
      pattern of five phosphopolypeptides of 70, 59, 56, 21 and 18 kDa, respectively.
      Peptide mapping of the five bands demonstrated that the same protein kinase
      substrates co-precipitated with both CD3 and CD5 and that the majority of the
      protein phosphorylation occurred on tyrosine residues. These data suggested that
      the TcR/CD3 complex and and the CD5 antigen might be associated in T cells.
      Evidence to support this hypothesis was obtained from analysis of
      immunoprecipitates prepared from surface-iodinated T cells. Bands characteristic
      of the TcR and CD3 antigens were identified in CD5 immunoprecipitates and
      conversely, CD5 was identified in CD3 immunoprecipitates. Conformation that CD3
      and CD5 co-precipitated in the presence of Brij96 was obtained by Western
      blotting. Quantitative immunodepletion demonstrated that between 10%-20% of cell
      surface CD5 was associated with the TcR/CD3 complex in Brij96 detergent lysates
      of human T cells and, furthermore, that this association was independent of T
      cell activation. The association of these two receptors provides a possible
      physical basis for the accessory role of the CD5 antigen in T cell activation.

PMID- 1385159
TI  - CD45RA-R0+ subset is the major population of dividing thymocytes in the human.
AB  - CD45, or leukocyte common antigen, is expressed in different isoforms on
      different subsets of thymocytes, suggesting its involvement in the process of T
      cell development in the thymus. We report studies on CD45 isoform expression on
      human thymocytes at various stages of development using three-color flow
      cytometric analysis and cell cycle analysis. Among CD45R0+ cells 18.4% were in
      S+G2/M phase and represented more than 80% of the dividing cells in the thymus.
      Among the CD45R0- cells 10.9% were also in cell cycle. Because the CD45R0+
      population is almost exclusively CD45RA-, the CD45RA-R0+ subset constitutes the
      major portion of dividing cells in the thymus. Both the CD1high and the CD3-
      populations were actively cycling. However, the former was almost 100% and the
      latter only 50% CD45RA-R0+. Dividing CD45RA-R0+ cells contain, therefore, many
      cells that have not yet expressed the CD3/T cell receptor complex and presumably
      have not yet undergone selective procedures. These results are hard to reconcile
      with the previously presented hypothesis that CD45R0 represents a marker for
      cells that are destined to die in the thymus. Instead, these results suggest an
      alternative possibility that CD45R0+ cells may contain cells that can mature and,
      thus, also constitute the thymic generative lineage.

PMID- 1385160
TI  - Intrathecal CP-96,345 blocks reflex facilitation induced in rats by substance P
      and C-fiber-conditioning stimulation.
AB  - We have examined the effects of intrathecally (i.t.) administered CP-96,345, a
      non-peptide NK1 receptor ligand, on the spinal nociceptive flexor reflex and on
      the facilitation of this reflex evoked by i.t. substance P (SP), neurokinin A
      (NKA) and electrical conditioning stimulation of cutaneous C-afferents. CP-96,345
      i.t. at 24 pmol-2.4 nmol had no significant effect on flexor reflex excitability.
      At the highest dose tested (24 nmol), CP-96,345 caused a brief facilitation of
      the flexor reflex, which was similar to the effect of the vehicle used at this
      drug concentration. CP-96,345 did not depress the flexor reflex at any dose. In
      rats with chronically implanted i.t. catheters, CP-96,345 at 24 nmol caused
      neither motor impairment nor morphological damage to the spinal cord.
      Pretreatment with CP-96,345 dose dependently and similarly antagonized
      facilitation of the flexor reflex induced by 7 pmol i.t. SP or by a 20-s, 1-Hz
      conditioning stimulus train applied to cutaneous C-fibers in the sural nerve
      innervation area. The vehicle had no effect. The antagonistic effect of CP-96,345
      on the SP- and C-fiber reflex facilitation induced by conditioning stimulation
      became maximal only 20-30 min after the i.t. injection and lasted 3-4 h at the
      highest dose. CP-96,345 did not significantly block the facilitatory effect of 7
      pmol i.t. NKA on the flexor reflex. These results demonstrate that CP-96,345 is a
      potent, long-lasting and selective antagonist of SP in rat spinal cord.
      Furthermore, facilitation of the flexor reflex (central sensitization) induced by
      conditioning stimulation of cutaneous C-afferents is mediated by NK1 tachykinin
      receptors, but the NK1 receptor may not be involved in the transmission of the
      flexor reflex. CP-96,345 is thus useful in experimental studies of the role of SP
      in the central nervous system.

PMID- 1385161
TI  - Enhancement in myocardial inotropic response to BAY K 8644 with advancing age.
AB  - In the present study, age-related alterations in cardiovascular response to Ca2+
      agonist BAY K 8644 were investigated in rats. Dose response of BAY K 8644 (1-30
      micrograms/kg) was studied in open chest rats by intravenous bolus
      administration. Maximum elevation of mean arterial pressure and (+)dp/dt of left
      ventricular pressure were significantly higher and the dose of BAY K 8644
      required to produce half maximal response was substantially lower in 12 months
      old (4 micrograms/kg) than in 2 months old (10 micrograms/kg) rats. Larger doses
      of BAY K 8644 produced arrhythmias only in 12 months old rats, which was not
      totally abolished by nitroglycerine pretreatment. Perfusion of isolated rat
      hearts with 10(-6) M BAY K 8644 produced positive inotropic response, which was
      on the average 50% greater and developed much faster in 12 months old than in 2
      months old rats. It is therefore concluded that the myocardial sensitivity to BAY
      K 8644 increases during adult maturation.

PMID- 1385162
TI  - The induction of nitric oxide synthase activity is inhibited by TGF-beta 1,
      PDGFAB and PDGFBB in vascular smooth muscle cells.
AB  - The effect of transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived
      growth factor (PDGF) was investigated on the induction of nitric oxide synthase
      activity caused by interleukin-1 beta in cultured smooth muscle cells from rat
      aorta. TGF-beta 1, PDGFAB and PDGFBB but not PDGFAA inhibited in a concentration
      dependent manner the production of nitrite, an oxidation product of nitric oxide,
      evoked by interleukin-1 beta. The growth factors alone did not stimulate the
      release of nitrite. The addition of interleukin-1 beta-treated smooth muscle
      cells to suspensions of indomethacin-treated human washed platelets inhibited the
      aggregation evoked by thrombin whereas no effect was observed with untreated
      cells. Platelet aggregation was not inhibited by smooth muscle cells that had
      been pretreated with interleukin-1 beta in combination with either TGF-beta 1,
      PDGFAB or PDGFBB but not with PDGFAA. These observations demonstrate that
      platelet-derived products such as TGF-beta and PDGFs inhibit the induction of
      nitric oxide synthase activity in vascular smooth muscle cells.

PMID- 1385163
TI  - Aging: inotropic effects of Bay K-8644 and nifedipine on rat cardiac muscle.
AB  - Inotropic effects of Bay K-8644, nifedipine, isoproterenol and extracellular
      calcium (Ca2+o) were examined in right ventricular strips, papillary muscle and
      left atria isolated from 4, 14 and 25 month old, male F344 rats. Under the
      experimental conditions used (37 degrees C, 1.4 mM Ca2+o and 4 Hz), control
      developed tension (expressed per mg wet weight) increased with age in right
      ventricular strips and papillary muscle, but decreased in left atria. The maximal
      positive inotropic response to Bay K-8644 was diminished with age in right
      ventricular strips and papillary muscle (but not left atria), while the negative
      inotropic action of nifedipine was not affected in any of the three tissues. Age
      decreased the inotropic efficacy of isoproterenol in right ventricular strips and
      papillary muscle (not left atria), had no effect on the efficacy of Ca2+o in
      right ventricular strips and left atria, but diminished the maximum response to
      Ca2+o in papillary muscle. Kd and B(max) values for [3H]nitrendipine binding were
      not significantly different in the three age groups. These data suggest: (1) that
      age-related changes in basal contractility and inotropic responsiveness differ in
      atrial and ventricular muscle; and (2) that these changes may result from
      alterations in excitation-contraction coupling which are not mediated by changes
      in Ca2+ channel density.

PMID- 1385165
TI  - Modulation of N-methyl-D-aspartate and (R,S)-alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionate (AMPA) responses of spinal nociceptive neurons by a
      N-terminal fragment of substance P.
AB  - The effects of an N-terminal fragment of substance P, substance P-(1-7) [SP-(1
      7)], on the responses of dorsal horn nociceptive neurons to N-methyl-D-aspartate
      (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) were
      tested by combined single-unit extracellular recordings/microiontophoresis. While
      SP-(1-7) had no effects when applied by itself, it was a potent and long-lasting
      modulator of both NMDA- and AMPA-mediated excitation of spinal dorsal horn
      nociceptive neurons. NMDA responses were transiently decreased (by an average of
      36% of control at minimum) by SP-(1-7) followed by a more sustained increase (by
      76% at maximum). In contrast, AMP responses were only increased by SP-(1-7) (by
      81% at maximum). It is hypothesized that the actions of SP-(1-7) on excitatory
      amino acid (EAA) responses of dorsal horn nociceptive neurons reflect a novel
      mechanism by which SP and EAAs interact to modulate pain transmission.

PMID- 1385164
TI  - Inhibitory action of neuropeptide Y on agonist-induced responses in isolated
      guinea pig trachea.
AB  - The effect of neuropeptide Y (NPY) was tested on isolated guinea pig trachea. At
      30 nM, NPY induced a weak but significant contractile response which was on
      average less than 6% of responses elicited by standard spasmogens. This myotropic
      action of NPY was blocked by indomethacin. In addition to its contractile
      activity, NPY greatly reduced the maximal response to vasoactive intestinal
      peptide (VIP), noradrenaline (NA), substance P (SP) and 5-hydroxytryptamine (5
      HT), without affecting their pD2 values. However, NPY did not influence the
      response induced by histamine and carbamylcholine. Pretreatment of tracheal
      spirals with indomethacin (10(-6) M) abolished the NPY-evoked inhibition of VIP,
      SP and 5-HT responses but failed to reduce the action of NPY on NA-elicited
      relaxation. This latter effect was however blocked in the presence of
      tetrodotoxin. In conclusion, NPY inhibits responses elicited by various agonists
      in the guinea pig trachea. This effect seems to be mediated at both pre- and
      postjunctional levels. The postjunctionally mediated inhibitory action of NPY
      appears to be expressed especially with agents that generate prostaglandins
      concomitantly with inducing their response. In contrast, the NPY-evoked
      inhibition of NA-evoked relaxation seems to be mediated via a prejunctional
      mechanism.

PMID- 1385166
TI  - Identification of a novel receptor mediating substance P-induced behavior in the
      mouse.
AB  - To determine whether opioid receptors or the more recently characterized naloxone
      sensitive substance P (SP) N-terminal binding sites play a role in
      desensitization to the behavioral effects of SP, we assessed the effects of
      selective antagonists at mu-(naloxonazine and beta-funaltrexamine), delta-
      (naltrindole) and kappa- (nor-binaltorphimine) opioid receptors, as well as the
      effect of [D-Pro2,D-Leu7]SP-(1-7) D-SP-(1-7) (D-SP (1-7)), an inhibitor of [3H]SP
      (1-7) binding, on behaviors induced by intrathecally administered SP in mice.
      Whereas naloxone, a non-selective opioid antagonist, inhibited the development of
      behavioral desensitization to SP, the response to repeated SP administration
      remained unaffected by pretreatment with selective opioid antagonists. Like
      naloxone, however, the SP-(1-7) antagonist inhibited SP-induced desensitization.
      The protection against desensitization to SP by D-SP-(1-7), but not by selective
      antagonists of mu, delta or kappa receptors, suggests that desensitization to the
      behavioral effects of SP does not appear to be mediated by an action at an opioid
      receptor but by an action at the SP-(1-7) binding site.

PMID- 1385167
TI  - Gastric prostaglandin E2 receptors are the common antisecretory target of mucosal
      prostanoids.
AB  - The gastric mucosa produces all principal prostaglandin (PG) types, but receptor
      binding studies in this tissue have as yet been performed exclusively with
      [3H]PGE2. Therefore we compared the binding of different 3H-labelled prostanoids
      to fundic mucosal plasma membranes from the porcine stomach. Binding sites for
      [3H]PGE2, [3H]iloprost and [3H]PGF2 alpha had similar nanomolar dissociation
      constants with high affinities for unlabelled PGE2. Iloprost and PGF2 alpha were
      10- and 100-fold less potent competitors with Hill slopes near unity in all
      cases. In further [3H]PGE2 competition studies the affinities of prostanoid
      ligands with selectivity for different PG receptor types correlated closely with
      their respective antisecretory potencies, as tested by [14C]aminopyrine uptake in
      isolated porcine parietal cells. We conclude that parietal cell PGE2 receptors
      are the common antisecretory target for all prostanoid types in the porcine
      stomach. There was no evidence for other mucosal PG receptors possibly involved
      in acid secretion.

PMID- 1385168
TI  - Nitric oxide mediates rat mucosal vasodilatation induced by intragastric
      capsaicin.
AB  - The role of endogenous nitric oxide (NO) in the gastric mucosal vasodilatation
      induced by acute intragastric perfusion with capsaicin or close-arterial infusion
      of rat alpha-calcitonin gene-related peptide (CGRP) was evaluated in the
      pentobarbitone-anaesthetised rat using laser Doppler flowmetry (LDF). The mucosal
      vasodilatation induced by intraluminal capsaicin (160 microM) was dose
      dependently reduced by the inhibitor of NO synthesis, NG-nitro-L-arginine methyl
      ester (L-NAME; 1-5 mg kg-1 i.v.), effects reversed by concurrent administration
      of L-arginine (100 mg kg-1 i.v.). L-NAME (2 mg kg-1) induced a small reduction in
      the mucosal vasodilatation induced by close-arterial infusion of rat alpha-CGRP
      (50 pmol kg-1 min-1). These findings indicate a role of NO in the gastric
      vasodilatation induced by stimulation of sensory neurones with intragastric
      capsaicin.

PMID- 1385169
TI  - The role of nitric oxide and platelet-activating factor in the inhibition by
      endotoxin of pentagastrin-stimulated gastric acid secretion.
AB  - Administration of E. coli endotoxin (1 mg/kg i.v.) abolished the acid secretory
      response induced by a bolus injection of pentagastrin (100 micrograms/kg i.v.) in
      the continuously perfused stomach of the anaesthetized rat. Endotoxin
      administration did not modify mean systemic arterial blood pressure. Pretreatment
      with NG-nitro-L-arginine methyl ester (L-NAME; 5-20 mg/kg i.v.), but not
      dexamethasone (5 mg/kg s.c. twice) or indomethacin (5 mg/kg i.m.), substantially
      restored the secretory responses to pentagastrin. The actions of L-NAME were
      reversed by the prior administration of L-arginine (100 mg/kg i.v.), but not by
      its enantiomer D-arginine (100 mg/kg i.v.). L-NAME (10 mg/kg i.v.) increased
      blood pressure but this does not seem to be the mechanism by which endotoxin
      induced acid inhibition was prevented, since similar systemic pressor responses
      induced by noradrenaline (15 micrograms/kg per min i.v.) had no such effect. The
      platelet-activating factor (PAF) receptor antagonist, WEB 2086 (2 mg/kg), induced
      a partial reversal of the inhibition by endotoxin of acid responses to
      pentagastrin. In endotoxin-treated rats, the combined administration of L-NAME
      (10 mg/kg) and WEB 2086 (2 mg/kg) completely restored the degree of H+ output
      induced by pentagastrin to levels similar to those of control, vehicle-treated
      animals. These findings suggest that endotoxin-induced acute inhibition of acid
      responses to pentagastrin involves NO synthesis and the release of PAF.

PMID- 1385170
TI  - Substance P injection into the dorsal raphe increases blood pressure and
      serotonin release in hippocampus of conscious rats.
AB  - Microinjections of substance P (SP, 100 pmol) into the dorsal raphe nucleus (DRN)
      in conscious rats increased blood pressure and heart rate for 30-40 min.
      Concomitantly, the extracellular levels of 5-hydroxytryptamine (5-HT) in the
      ventral hippocampus, monitored by microdialysis, increased by 30% for 20 min
      compared with the vehicle control. Pretreatment with the 5-HT2 receptor
      antagonist, ritanserin (1 mg/kg i.v.), prevented the pressor response to SP but
      not the increase in heart rate. Pretreatment with the partial 5-HT1A receptor
      agonist, 8-methoxy-2-(N-2-chloroethyl-N-n-propyl)amino tetralin (8-MeO-CLEPAT, 10
      micrograms/kg i.v.) prevented the increase in both blood pressure and heart rate.
      It is suggested that microinjections of SP into the DRN increase blood pressure
      through activation of serotonergic DRN neurons and that the postsynaptic receptor
      responsible for the pressor response is of the 5-HT2 type.

PMID- 1385171
TI  - Effects of a unilateral 6-hydroxydopamine lesion and prolonged L-3,4
      dihydroxyphenylalanine treatment on peptidergic systems in rat basal ganglia.
AB  - The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion of the medial
      forebrain bundle or of a sham lesion on the neuropeptide content of the striatum
      and substantia nigra was investigated with or without 6 months L-3,4
      dihydroxyphenylalanine (L-DOPA; 200 mg/kg per day) plus carbidopa (25 mg/kg per
      day) treatment. [Met5]- and [Leu5]enkephalin, substance P (SP), neurotensin (NT)
      and cholecystokinin (CCK) were measured by a combined HPLC/RIA method.
      Neurotensin levels were increased in the striatum, and [Leu5]enkephalin, and SP
      levels were reduced in the substantia nigra as a consequence of the lesion, while
      the levels of other peptides were unaltered. Administration of L-DOPA to sham
      operated rats bilaterally increased SP levels in striatum and substantia nigra,
      and [Met5]enkephalin and CCK content in substantia nigra. L-DOPA treatment of 6
      OHDA-lesioned rats increased [Met5]- and [Leu5]enkephalin and CCK levels in the
      striatum ipsilateral to the lesion but not on the intact side. In the substantia
      nigra, the lesion-induced decrease in [Leu5]enkephalin and SP was reversed by L
      DOPA treatment, [Met5]enkephalin and CCK levels ipsilateral to the lesion were
      further enhanced, and there was an increase in NT ipsilateral to the lesion.
      Cryptic [Met5]- and [Leu5]enkephalin increased in the ipsilateral striatum
      following an 6-OHDA lesion. L-DOPA treatment did not alter cryptic enkephalin
      levels or the lesion-induced increase in cryptic [Met5]enkephalin, while cryptic
      [Leu5]enkephalin was further increased in lesioned animals given L-DOPA. These
      results suggest that the pattern of change in basal ganglia peptides in
      Parkinson's disease is not due solely to the destruction of the nigrostriatal
      pathway, the drug treatment of the disease or a combination of these factors.

PMID- 1385172
TI  - Effects of cold stress on some 5-HT1A, 5-HT1C and 5-HT2 receptor-mediated
      responses.
AB  - The purpose of the present study was to analyze the influence of stress (24-h
      cold exposure) on presynaptic 5-HT1A receptors, and on postsynaptic 5-HT1A, 5
      HT1C and 5-HT2 receptors. Cold exposure for 24 h affected neither pargyline
      induced decreases in 5-hydroxyindoleacetic acid (5-HIAA) levels in midbrain and
      rest of brain, nor plasma glucose and corticosterone levels. Treatment with the 5
      HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.5-1
      mg/kg), 3-5 h after the end of cold exposure triggered less intense flat body
      posture and forepaw treading in cold-exposed rats than in controls. On the other
      hand, 15- and 30-min plasma glucose responses to 8-OH-DPAT (0.25-0.5 mg/kg, 3-5 h
      after cold) or to the alpha 2-adrenoceptor agonist, clonidine (0.025 mg/kg), were
      not affected by cold, while the 15-min, but not the 30 min, plasma corticosterone
      response to 8-OH-DPAT was slightly amplified in cold-exposed rats. Cold exposure
      affected neither the inhibitory effect of 8-OH-DPAT (0.25-0.5 mg/kg, 3-5 h after
      cold) on midbrain 5-HIAA levels, nor the hypothermic effect of 8-OH-DPAT (0.5-1
      mg/kg, 3-5 h after cold). Lastly, the hypoactivity elicited by the 5-HT1C
      receptor agonist, m-chlorophenyl-piperazine (1.5-3 mg/kg, 3-5 h after cold), or
      head shakes elicited by the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane (1-2 mg/kg, 3-5 h after cold), were of similar
      intensities in control and in cold-exposed rats.

PMID- 1385173
TI  - Endothelium-accelerated hyporesponsiveness of norepinephrine-elicited contraction
      of rat aorta in the presence of bacterial lipopolysaccharide.
AB  - The role of the endothelium in the hyporesponsiveness of alpha-adrenoceptor
      mediated contractions of the rat aorta was investigated. The norepinephrine
      induced maximal contraction was diminished after repeated addition of the
      agonist. The hyporesponsiveness of the maximal contraction was endothelium
      dependent, being prevented by NG-monomethyl-L-arginine (0.5 mM), L
      argininosuccinic acid (0.5 mM), puromycin (IC50 = 100 microM), actinomycin D
      (IC50 = 80 nM) but not by indomethacin, which suggests that nitric oxide (NO)
      synthase is induced. The sensitivity of the rings to NO-induced relaxation
      remained unchanged. The above-mentioned hyporesponsiveness of norepinephrine
      induced maximal contractions of aorta rings was also observed after a 5-h
      incubation without norepinephrine. The agonist-independent hyporesponsiveness was
      also prevented by NG-monomethyl-L-arginine, puromycin and actinomycin D, which
      suggests that NO synthase is induced. Moreover, the norepinephrine-independent
      hyporesponsiveness was prevented by polymyxin B (10 micrograms/ml), which
      suggests that bacterial lipopolysaccharide (LPS) might be involved. The
      concentration of contaminating LPS was 89 +/- 11 ng/ml. When the concentration of
      contaminating LPS was reduced to 40-70 pg/ml, the hyporesponsiveness of the
      maximal contraction did not occur after repeated addition of norepinephrine or
      alter a 5-h incubation without the agonist. An addition of 30 or 100 ng/ml of E.
      coli lipopolysaccharide to the organ bath reproduced the hyporesponsiveness of
      the maximal contraction. After a 5-h incubation of aortic rings with 30 ng/ml
      LPS, only the endothelium-intact ring showed a reduced contraction. However, a 24
      h incubation reduced the contraction even in the absence of endothelium.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1385174
TI  - Sex difference for tolerance of 5-HT1A receptor-mediated temperature and
      corticosterone responses in mice.
AB  - Repeated treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)
      resulted in significant attenuation of 8-OH-DPAT-induced hypothermia and
      adrenocorticol effect in mice of both sexes, while it did not affect the 8-OH
      DPAT-induced decrease in 5-hydroxyindoleacetic acid in the hypothalamus in either
      sex. The attenuated responses developed more rapidly in female than in male mice,
      indicating sex differences in the adaptive regulation of the 5-HT1A receptor
      mediated responses.

PMID- 1385175
TI  - Actions of a metabotropic glutamate receptor agonist in immature and adult rat
      cerebellum.
AB  - The electrophysiological actions of the metabotropic glutamate receptor agonist
      1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on Purkinje and granule
      cells were studied in immature and adult cerebellar slices. ACPD elicited a
      depolarising response when applied to Purkinje cells (EC50 approximately 20
      microM). Granule cells hyperpolarised when exposed to low (3-10 microM)
      concentrations of ACPD; higher concentrations produced a depolarisation (EC50
      approximately 40 microM) that was rapidly curtailed by a hyperpolarisation. The
      hyperpolarisation was abolished when Ca2+ was removed. In Purkinje cells, the
      amplitude of the depolarisation was greater in adult slices compared to those in
      immature slices. The responses were not blocked by ionotropic glutamate receptor
      antagonists or (L)-2-amino-3-phosphonopropionate (AP3).

PMID- 1385176
TI  - Identification of the central tachykinin receptor subclass involved in substance
      P-induced cardiovascular and behavioral responses in conscious rats.
AB  - To identify the tachykinin receptor subclass involved in the central
      cardiovascular and behavioral actions of substance P (SP), we compared the
      central actions of SP with those of neurokinin A (NKA) and senktide in conscious
      chronically instrumented rats. Intracerebroventricular (i.c.v.) injection of SP
      (an NK1 agonist) and NKA (an NK2 agonist) increased mean arterial pressure (MAP)
      and heart rate (HR) dose dependently and these cardiovascular responses were
      associated with the behavioral responses, comprising excessive grooming and
      exploring. Both peptides were equipotent to produce the cardiovascular and the
      behavioral responses. Senktide (a highly selective NK-3 agonist), injected i.c.v.
      increased the HR markedly. The behavioral response, 'wet dog shakes', was
      observed most frequently after senktide and was dissociated from the HR response.
      Pretreatment with a peripheral NK-1-selective antagonist, L-668,169, attenuated
      the NKA-induced cardiovascular and behavioral responses but not the SP-induced
      responses. However, pretreatment with a peripheral NK-2-selective antagonists, L
      659,877, attenuated the SP-induced responses but not the NKA-induced responses.
      These results suggest that the central cardiovascular and behavioral actions of
      SP and NKA are mediated by different subclasses of receptors and that the
      receptor subclasses which are specific for the central nervous system differ from
      those which mediate the peripheral actions of the two tachykinins.

PMID- 1385177
TI  - The substance P receptor antagonist CP-96,345 interacts with Ca2+ channels.
AB  - The nonpeptide substance P receptor antagonist CP-96,345 was found to displace
      binding to Ca2+ channel binding sites labelled with either
      [3H]desmethoxyverapamil or [3H]diltiazem and to enhance [3H]nitrendipine binding.
      Unlike the substance P receptor antagonist activity of CP-96,345, these effects
      on Ca2+ channel binding sites were neither stereoselective nor species-dependent.
      It is concluded that CP-96,345 may act as an antagonist of L-type Ca2+ channels
      in addition to being a potent NK1 receptor (substance P) antagonist.

PMID- 1385178
TI  - Ca2+ channel inhibition in a rat osteoblast-like cell line, UMR 106, by a new
      dihydropyridine derivative, S11568.
AB  - UMR 106 rat osteogenic sarcoma cells were studied with the whole cell patch clamp
      technique to investigate the presence of voltage-gated inward currents. In barium
      (Ba2+)-containing medium, depolarizing jumps revealed both transient (T-type) and
      sustained (L-type) Ba2+ currents. The L-type component was dihydropyridine
      sensitive: the agonist Bay K 8644 increased the amplitude of the L-type Ba2+
      current. A new dihydropyridine calcium channel blocker, S 11568 ((+/-)-2(2-[2
      (aminoethoxy)ethoxyl]methyl)4-(2',3'- dichlorophenyl)3-ethoxycarbonyl-5
      methoxycarbonyl-6-methyl-1,4- dihydropyridine, and its enantiomers, S 12967 ((+)
      S 11568) and S 12968 ((-)-S 11568), inhibited the L-type Ba2+ current. IC50
      values at a holding potential (VH) of -50 mV were 90 nM for S 11568, 800 nM for S
      12967 and 45 nM for S 12968. At VH = -80 mV, S 12968 was less potent (IC50 near
      500 nM). In contrast, S 12968 was without appreciable effect on the T-type
      component of the inward current through Ca2+ channels. Our results indicate that
      UMR 106 cells express both T-type and L-type Ca2+ channels and could be used to
      study the modulation by Ca2+ channel blocking agents, such as S 12968, of the
      hormonal regulation of Ca2+ fluxes across the osteoblast membrane.

PMID- 1385179
TI  - AE0047, a new dihydropyridine Ca2+ entry blocker, inhibits the responses to
      adrenergic nerve stimulation and substance P in dog mesenteric arteries.
AB  - AE0047, a new dihydropyridine-type Ca2+ entry blocker, significantly inhibited
      the contractions induced by transmural electrical stimulation and norepinephrine
      in dog mesenteric artery strips. The inhibition was greater in the case of the
      response to nerve stimulation. The 3H-overflow ratio evoked by electrical
      stimulation from strips previously soaked in [3H]norepinephrine was significantly
      reduced by AE0047 but not by nicardipine in a concentration sufficient to
      attenuate the response to norepinephrine. In aorta homogenate preparations,
      [3H]bunazosin binding was not replaced by AE0047 but by phentolamine. In strips
      treated with indomethacin, the endothelium-dependent relaxation caused by
      substance P and bradykinin was attenuated by treatment with AE0047 but not with
      nicardipine. The nitric oxide (NO)-induced relaxation was not influenced by
      AE0047. Cyclic GMP levels in the artery strips increased in response to substance
      P; the increase was markedly suppressed by AE0047 but not by nicardipine. In
      contrast to nicardipine, AE0047 appeared to inhibit the release of norepinephrine
      from adrenergic nerves and of NO from endothelial cells. The inhibition may be
      associated with the decreased transmembrane influx of Ca2+ in these tissues.

PMID- 1385180
TI  - The isolated spinal cord-skin preparation of the newborn rat and effects of some
      algogenic and analgesic substances.
AB  - We have developed an isolated spinal cord-skin preparation of the newborn rat.
      The spinal cord together with a piece of skin connected to the cord by the
      saphenous nerve was isolated from 1- to 4-day-old rats and separately superfused
      with artificial cerebrospinal fluid in two neighbouring chambers. Potentials were
      recorded extracellularly from the third lumbar ventral root. Application of
      capsaicin (0.5-2 microM) or KCl (60-350 mM) with brief pressure pulses to the
      perfusion bath of the skin evoked a depolarizing response of 20- to 40-s duration
      in the ventral root. The response was depressed by [Met5]enkephalin (0.03-3
      microM), morphine (0.1-2 microM) and a tachykinin antagonist, [D-Arg1,D
      Trp7,9,Leu11] substance P (spantide), (1-10 microM), applied to the spinal cord
      by superfusion, whereas the response was augmented by centrally administered
      calcitonin gene-related peptide (0.1-0.2 microM) or bicuculline (0.5-1 microM).

PMID- 1385181
TI  - The influence of neuraminidase treatment on tracheal smooth muscle contraction.
AB  - To examine the role of sialic acid in the respiratory tract, the influence of
      neuraminidase from Clostridium perfringens was investigated on contractions of
      isolated guinea-pig and rat trachea and on histamine release from guinea-pig lung
      tissue. Treatment with 2.0 units/ml of neuraminidase at 37 degrees C and pH 7.4
      for 30 min caused an approximately 60% removal of total N-acetylneuraminic acid,
      a representative sialic acid, from muscle from guinea-pig and rat trachea.
      Neuraminidase concentration dependently induced histamine release from guinea-pig
      chopped lung tissue, but has no effect on contractions produced by acetylcholine,
      histamine and 5-hydroxytryptamine. Pretreatment with 2.0 units/ml of
      neuraminidase inhibited the contraction induced by antigen (ovalbumin) or
      compound 48/80. These findings suggest, at least in part, that sialic acids
      sensitive to neuraminidase are involved in the regulation of histamine release
      but not tracheal contraction.

PMID- 1385182
TI  - Effects of L- and N-type Ca2+ channel antagonists on excitatory amino acid-evoked
      dopamine release.
AB  - In the present study we tested the effect of dihydropyridine (DHP) Ca2+ channel
      antagonists and of omega-conotoxin GVIA on [3H]dopamine (DA) release evoked by
      the activation of excitatory amino acid (EAA) receptors in cultures of fetal rat
      ventral mesencephalon, in order to investigate the role of voltage-sensitive L-
      and N-type Ca2+ channels in these EAA-mediated processes. Micromolar
      concentrations (10-30 microM) of DHP L-type Ca2+ channel antagonists inhibited
      [3H]DA release evoked by N-methyl-D-aspartate (NMDA), kainate, quisqualate or
      veratridine. [3H]DA release evoked by the L-type Ca2+ channel agonist, Bay K
      8644, was inhibited by lower concentrations (0.1-1 microM) of the DHP antagonist,
      nitrendipine, than was the release evoked by EAAs. The DHP antagonist, (+)-PN 200
      110, was more potent than (-)-PN 200-110 in inhibiting [3H]DA release evoked by
      Bay K 8644, but the two stereoisomers were equipotent in inhibiting NMDA-evoked
      release. These results indicate that activation of L-type Ca2+ channels is able
      to evoke [3H]DA release. However activation of L-type channels is not involved in
      EAA-induced [3H]DA release and therefore inhibition of EAA-induced [3H]DA release
      by micromolar concentrations of DHPs must be mediated by actions other than
      inhibition of L-type Ca2+ channels. omega-Conotoxin GVIA (3 microM) had no effect
      on [3H]DA release evoked by Bay K 8644, indicating that the toxin may selectively
      inhibit N-type channels in this preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385183
TI  - Behavioral and pharmacological effects of centrally administered aminooxyacetic
      acid in rats.
AB  - In the present experiment unilateral intrastriatal injections of aminooxyacetic
      acid (1, 2.5, 5 mumol) to freely moving animals and pentobarbital-anesthetized
      rats produced contralateral jerks and dose-dependent mortality, but no barrel
      rotation. At 10-12 days there were no significant differences in exploratory
      activity, passive avoidance behavior, and elevated plus-maze test in
      aminooxyacetic acid-treated animals as compared with controls. However freely
      moving animals microinjected with aminooxyacetic acid (but not the pentobarbital
      pretreated group) had impaired learning activity in an active avoidance
      conditioning test, and showed reduced striatal concentrations of substance P and
      GABA. Intrastriatal injections of aminooxyacetic acid therefore result in both
      acute and chronic behavioral changes which are attenuated by pentobarbital
      anesthesia.

PMID- 1385184
TI  - 4C3HPG (RS-4-carboxy-3-hydroxyphenylglycine), a weak agonist at metabotropic
      glutamate receptors, occludes the action of trans-ACPD in hippocampus.
AB  - The determination of the physiological role of glutamatergic metabotropic actions
      has been hampered by the lack of potent and specific antagonists. It has recently
      been reported that 4C3HPG (RS-4-carboxy-3-hydroxyphenylglycine) can antagonize
      metabotropic responses in the central nervous system. The effects of 4C3HPG on
      metabotropic responses evoked by trans-ACPD were investigated in CA3 pyramidal
      cells in hippocampal slice cultures. Our results show that in hippocampus 4C3HPG
      fails to antagonize responses mediated by metabotropic glutamate receptors.

PMID- 1385186
TI  - Anaesthetic doses of pentobarbital antagonize phosphatidylinositol hydrolysis
      induced by substance P or carbachol in the spinal cord and cerebral cortex of the
      rat.
AB  - Basal as well as agonist (100 microM substance P or 2 mM carbachol)-stimulated
      phosphatidylinositol hydrolysis was investigated in slices of rat spinal cord and
      cerebral cortex, in the presence and absence of pentobarbital (5-50 microM in
      vitro or 65 mg/kg in vivo) or urethane (0.2 mM in vitro or 1.4 g/kg in vivo).
      Urethane was without effect; pentobarbital, however, inhibited the basal
      hydrolysis and the agonist-stimulated phosphatidylinositol hydrolysis (in dose
      dependent fashion in vitro). It is suggested that inhibition of
      phosphatidylinositol hydrolysis may be part of the cellular mechanisms by which
      pentobarbital produces anaesthesia.

PMID- 1385185
TI  - Thiol group identification at or near the agonist binding site of the vascular
      dopamine receptor.
AB  - Cultured mesenteric artery vascular smooth muscle cells derived from male Wistar
      rats, expressing both beta 2-adrenoceptors and dopamine DA1 receptors, were
      prelabelled for 2 h with [3H]adenine. [3H]cAMP formation stimulated by the
      addition of dopamine (plus propranolol 10 microM), isoprenaline or forskolin, in
      the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      (IBMX) (0.5 mM) was then determined. Exposure of cells to the thiol-oxidizing
      agent DTNB (5,5'-dithiobis-2-nitrobenzoic acid) following prelabelling, and prior
      to cAMP assay, resulted in a time-dependent inhibition of dopamine (0.1 mM)
      induced cAMP formation, which obeyed the rules of first-order kinetics, being
      complete by 60 min. This inhibitory effect was observed to be dose related with
      50% inhibition achieved at a concentration of 0.5 mM. Exposure to DTNB (5 mM) for
      45 min abolished the cAMP response to dopamine (0.1 mM) with little effect on the
      response to forskolin (10 microM) or isoprenaline (10 microM). Prior addition of
      the dopamine DA1/D1 receptor selective partial agonist (+)-SKF 38393 (1 microM)
      preserved the dopamine induced cAMP formation despite DTNB exposure, while its
      stereo-enantiomer (-)-SKF 38393 (1 microM) protected only 25% of the response.
      Sequential exposure of cells to DTNB (5 mM) and then either vehicle or DTT (DL
      dithiothreitol; 1 mM), each for 20 min periods, resulted in a 70% inhibition of
      dopamine induced cAMP formation which was almost completely reversed by the
      disulphide bridge cleaving compound DTT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385187
TI  - Polyamine spider toxins are potent un-competitive antagonists of rat cortex
      excitatory amino acid receptors.
AB  - We examined the effect of argiopine and argiopinine 3, low molecular weight
      polyamine venom components of the spider Argiope lobata, on rat cortical
      excitatory amino acid (EAA) receptors expressed in Xenopus oocytes. Responses to
      100 microM N-methyl-D-aspartate (NMDA) with 10 microM glycine were blocked by
      both of the polyamine toxins in a dose-dependent manner. Both compounds had
      similar potencies against 100 microM kainate or 50 microM (S)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (L-AMPA). Oscillatory responses to 2
      microM quisqualate were unaffected by either polyamine toxin. Increasing
      concentrations of either NMDA, kainate or AMPA were unable to overcome the
      antagonism by either spider toxin. We were able to demonstrate a use-dependent
      phenomenon similar to that of phencyclidine; neither polyamine toxin affected the
      NMDA, kainate or AMPA response without the presence of the respective agonist.

PMID- 1385188
TI  - Effects of the extracellular matrix on fetal choroid plexus epithelial cells:
      changes in morphology and multicellular organization do not affect gene
      expression.
AB  - We have developed a primary culture system for fetal mouse choroid plexus
      epithelial cells which maintains their differentiated phenotype. When grown on a
      reconstituted basement membrane substrate (Matrigel) epithelial cells formed
      aggregates which became embedded in the matrix and developed into characteristic
      and highly reproducible multicellular vesicular structures. These vesicles
      consisted of a squamous layer of epithelial cells with extensive attachment to
      the matrix substrate, surrounding a fluid-filled lumen. Electron microscopy
      showed that cells comprising these vesicles had a high degree of membrane
      specialization and polarized morphology which in many respects mimicked the in
      vivo morphology. Biochemical analyses demonstrated that under these culture
      conditions the tissue-specific pattern of gene expression of fetal choroid plexus
      epithelium was maintained. After 6 days in culture these cells contained
      approximately the same amount of transthyretin mRNA as the 12.5-day choroid
      plexus in vivo, and the level of total RNA per cell, which is proportional to the
      protein synthetic capability of the cells, was also maintained. The pattern of
      protein secretion was also very similar to that generated by fetal mouse choroid
      plexus cells in vivo. In contrast choroid plexus epithelial cells attached poorly
      to collagen I gels. Heterogeneous aggregates were formed in which cell-cell
      interactions were more extensive than cell-substrate interactions, and in no
      cases was a central lumen observed. Cells on the surface of large aggregates
      showed some evidence of membrane polarization, while the majority of cells in the
      cultures exhibited little evidence of polarized morphology. Despite the striking
      difference in morphology and multicellular organization these cells still
      expressed high levels of transthyretin mRNA and maintained the same pattern of
      protein synthesis as cells cultured on Matrigel. These results indicate that the
      basement membrane is important for the organization of choroid plexus epithelial
      cells into a functional epithelium in vitro and thus presumably the maintenance
      of the integrity of the blood-brain barrier in vivo. In contrast to several other
      epithelial systems which have been studied, the type of extracellular matrix does
      not appear to directly influence tissue-specific gene expression by choroid
      plexus epithelial cells. Thus the level of gene expression is not dependent on
      the cytoarchitecture and multicellular organization of this cell type.

PMID- 1385189
TI  - Identification of Tetrahymena 14-nm filament-associated protein as elongation
      factor 1 alpha.
AB  - Tetrahymena 14-nm filament-forming protein has dual functions as a citrate
      synthase in mitochondria and as a cytoskeletal protein involved in oral
      morphogenesis and in pronuclear behavior during conjugation. By immunoblotting
      using monoclonal and polyclonal antibodies following two-dimensional gel
      electrophoresis, we demonstrated that the 14-nm filament protein fraction
      contained two 49-kDa proteins whose isoelectric points were 8.0 and 9.0; a
      monoclonal antibody (MAb) 26B4 and a polyclonal antibody 49KI reacted only to a
      pI 8.0 protein, while two other MAbs, 11B6 and 11B8, reacted only to a pI 9.0
      protein. From the N-terminal amino acid sequences, the pI 8.0 protein was
      identified as the previously reported 14-nm filament-forming protein/citrate
      synthase, but the pI 9.0 protein N-terminal sequence had no similarity with that
      of the pI 8.0 protein. The pI 9.0 protein is considered to be a 14-nm filament
      associated protein since the pI 9.0 protein copurifies with the pI 8.0 protein
      during two cycles of an assembly and disassembly purification protocol. Cloning
      and sequencing the pI 9.0 protein gene from a Tetrahymena pyriformis cDNA
      library, we identified the pI 9.0 protein as elongation factor 1 alpha (EF-1
      alpha) based on it sharing 73-76% sequence identity with EF-1 alpha from several
      species.

PMID- 1385190
TI  - Nucleolin is an Ag-NOR protein; this property is determined by its amino-terminal
      domain independently of its phosphorylation state.
AB  - The Ag-NOR proteins are defined as markers of "active" ribosomal genes. They
      correspond to a set of proteins specifically located in the nucleolar organizer
      regions (NORs), but have not yet been clearly identified. We adapted the specific
      detection method of the Ag-NOR proteins to Western blots in order to identify
      these proteins. Using a purified protein, Western blots, and immunological
      characterization, the present study brings the first direct evidence leading to
      the identity of one Ag-NOR protein. We found that nucleolin is specifically
      revealed by Ag-NOR staining. Using different nucleolin fragments generated by
      CNBr cleavage and by overexpression in Escherichia coli, we demonstrate that the
      amino-terminal domain of nucleolin and not the carboxy-part of the protein is
      involved in silver staining. Moreover, as the pattern of staining does not vary
      using casein kinase II- and cdc2-phosphorylated nucleolin or dephosphorylated
      nucleolin, we conclude that the reduction of the silver ions is not linked to the
      phosphorylation state of the molecule. We propose that the concentration of
      acidic amino acids in the amino-terminal domain of nucleolin is responsible for
      Ag-NOR staining. This hypothesis is also supported by the finding that poly L
      glutamic acid peptides are silver stained. These results provide data that can be
      used to explain the specificity of Ag-NOR staining. Furthermore, we clearly
      establish that proteolysis of the amino-terminal Ag-NOR-sensitive part of
      nucleolin occurs in vitro, leading to the accumulation of the carboxy-terminal Ag
      NOR-negative part of the protein. We argue that this cleavage occurs in vivo as
      already proposed, bearing in mind that nucleolin is present in the fibrillar and
      in the granular component of the nucleolus, whereas no Ag-NOR staining is
      observed in the latter nucleolar component.

PMID- 1385191
TI  - Localization of a 215-kDa tyrosine-phosphorylated protein that cross-reacts with
      tensin antibodies.
AB  - Tyrosine phosphorylation of cytoskeletal proteins at adhesive junctions has been
      speculated to play a role in the regulation of cell signaling at these sites.
      Previously, monoclonal antibodies were generated against phosphotyrosine
      containing proteins from Rous sarcoma virus-transformed chick embryo fibroblasts,
      resulting in two antibodies which recognized antigens of 76 and 215 kDa that
      localized to focal contacts. We have now localized the 215-kDa antigen to a
      number of adhesive junctions in vivo, including the zonula adherens, intercalated
      discs, and myotendinous and neuromuscular junctions. In sections of skeletal
      muscle and in isolated myofibrils, the 215-kDa protein was localized to the I
      band. By immunoprecipitation and immunoblot analysis, we determined that the 215
      kDa antigen cross-reacts with a polyclonal anti-tensin antibody.

PMID- 1385192
TI  - Platelet-derived growth factor (PDGF) receptor activation in cell transformation
      and human malignancy.
AB  - We demonstrate that the v-sis-transformed NIH/3T3 fibroblasts exhibit tyrosine
      phosphorylation of both intracellular and cell surface forms of the alpha and
      beta platelet-derived growth factor (PDGF) receptors (PDGFRs). Cell proliferation
      was partially inhibited by PDGF-neutralizing antibody, but was completely blocked
      by the drug suramin. Suramin treatment markedly reduced tyrosine-phosphorylated
      cell surface PDGFRs, but had no effect on the tyrosine-phosphorylated
      intracellular receptor species. These findings indicate that v-sis-activated
      PDGFRs must attain a cell surface localization to functionally couple with the
      mitogenic-signaling pathway. Additionally, we were able to demonstrate a
      functional autocrine loop involving PDGF in human tumor cell lines. Exposure to
      suramin resulted in diminished receptor autophosphorylation and/or upregulation
      of the PDGFRs. A subset of the tumor cell lines possessing a PDGF autocrine
      pathway exhibited a significant reduction in proliferation after exposure to
      suramin. These findings indicate that a PDGF autocrine loop contributes to the
      uncontrolled proliferative drive in some human malignancies.

PMID- 1385193
TI  - Simian switching suggests solution to the symptoms of the sickle cell syndromes.

PMID- 1385195
TI  - Reversible inhibitory effects and absence of toxicity of the tetrapeptide acetyl
      N-Ser-Asp-Lys-Pro (AcSDKP) in human long-term bone marrow culture.
AB  - The effects of acetyl-N-Ser-Asp-Lys-Pro (Ac-SDKP) in human long-term bone marrow
      cultures (LTBMCs) were assessed by measuring the number of progenitors and the
      development of stromal cells over a 6-week course. In a first set of experiments,
      AcSDKP was added weekly at each medium change. Under these conditions, no
      significant effect of the peptide was observed. In contrast, by adding AcSDKP
      daily at 10(-10) M, the growth of the progenitors of the non-adherent (NA)
      compartment was inhibited by about 35%. This inhibition was entirely reversible;
      after stopping the addition of the peptide at the fourth week, the number of
      progenitors returned to control level within 2 weeks. Conversely, AcSDKP did not
      significantly change the number of the progenitors present in the adherent layer.
      In addition, AcSDKP did not affect the formation of the stromal layer nor induce
      the secretion of cytokines, such as tumor necrosis factor alpha (TNF-alpha),
      interleukin 1 beta (IL-1 beta), granulocyte colony-stimulating factor (G-CSF),
      interleukin 3 (IL-3), or interleukin 6 (IL-6). Our results indicate that AcSDKP
      has inhibitory but reversible effects on NA progenitors and does not induce long
      term modifications of the microenvironment, both of particular interest for its
      clinical application.

PMID- 1385196
TI  - Combined measurement of growth and differentiation in suspension cultures of
      purified human CD34-positive cells enables a detailed analysis of myelopoiesis.
AB  - In this study we have made a detailed analysis of growth factor (granulocyte
      macrophage colony-stimulating factor [GM-CSF], granulocyte colony-stimulating
      factor [G-CSF], and macrophage colony-stimulating factor [M-CSF])-induced
      proliferation and differentiation of highly purified CD34+ committed human
      myeloid progenitor cells in suspension cultures. The results were compared with
      colony formation in semisolid medium. Proliferation in suspension cultures was
      determined by means of incorporation of [3H]thymidine, differentiation by flow
      cytometric immunophenotyping using a panel of monoclonal antibodies against
      monomyeloid antigens, and by morphology. A good correlation was found between the
      number of granulocyte-macrophage colony-forming units (CFU-GM) in semisolid
      medium and [3H]thymidine incorporation in suspension (r = 0.82), both assessed at
      day 11. Moreover, the frequency of proliferating cells as determined in
      suspension cultures by limiting dilution analysis was similar to the frequencies
      of CFU-GM as measured in semisolid medium. Studies on GM-CSF- and G-CSF-induced
      cell-growth kinetics revealed distinct proliferation patterns.
      Immunophenotypically the subsequent induction of the mature granulocytic antigens
      CD15 and CD67 was observed to be accompanied by a gradual loss of the HLA-DR
      antigen, whereas little monocytic differentiation was observed. M-CSF, although
      inducing no colony formation of CD34+ cells and minimal proliferation in
      suspension, induced monocytic differentiation, demonstrated by the expression of
      HLA-DR, CD14, and CD36 in the absence of CD15 and CD67. The observed
      immunophenotypical profiles were confirmed by the results of cytological
      characterization. Thus, the combined measurement of growth factor-induced
      proliferation and differentiation of progenitor cells in suspension cultures can
      be a useful alternative for the CFU-GM assay. Moreover, because small numbers of
      cells are required, it allows for detailed studies on cell-growth kinetics and
      developmental stages within the granulocytic and monocytic lineages.

PMID- 1385194
TI  - Hydroxyurea-induced HbF production in anemic primates: augmentation by
      erythropoietin, hematopoietic growth factors, and sodium butyrate.
AB  - Hydroxyurea, a cell-cycle-specific cytotoxic agent, has been shown to increase
      fetal hemoglobin (HbF) production. This property makes it an attractive drug for
      treatment of sickle cell disease and severe beta thalassemia. Its potential
      efficacy is limited because of a variable and often suboptimal response.
      Combinations of hydroxyurea and other drugs may induce more clinically
      significant increases in HbF. We have utilized chronically phlebotomized rhesus
      monkeys, treated with oral hydroxyurea, to investigate the capacity of several
      other agents to further augment HbF synthesis. Recombinant human erythropoietin,
      in super-pharmacologic doses, increased F-reticulocyte production when given on a
      weekly sequential schedule (3 of 7 days) with hydroxyurea (4 of 7 days), but it
      was less effective on an alternate day schedule when hydroxyurea was given daily.
      Neither recombinant human interleukin 3 (IL-3) nor recombinant human granulocyte
      macrophage colony-stimulating factor (GM-CSF), when infused individually,
      increased F-reticulocytes in animals receiving daily hydroxyurea. Sequential,
      overlapping infusions of IL-3 and GM-CSF produced a small but statistically
      significant increase in F-reticulocytes in one of two hydroxyurea-treated
      animals. Infusions of sodium butyrate produced a substantial augmentation in F
      reticulocyte production in animals chronically treated with hydroxyurea. Thus,
      our studies have identified several agents that may prove useful in combination
      with hydroxyurea to achieve clinically beneficial levels of HbF.

PMID- 1385197
TI  - Synergistic suppression of the clonogenicity of U937 leukemic cells by
      combinations of recombinant human interleukin 4 and granulocyte colony
      stimulating factor.
AB  - The actions and interactions of purified recombinant human (rh) interleukin 4 (IL
      4) and granulocyte colony-stimulating factor (G-CSF) on the clonogenicity of
      human leukemic cell line U937 were studied in vitro. Parameters analyzed were the
      suppression of stem cell generation using sequential clonal cultures, alterations
      of surface antigen expression, and morphological changes. IL-4 alone (10 U/ml)
      and G-CSF alone (1000 U/ml) only slightly reduced colony numbers (80% +/- 7% and
      87% +/- 7% of control colonies, respectively). However, IL-4 interacted
      synergistically with G-CSF to further reduce the colony number (46% +/- 8% of
      control colonies) and suppress the self-renewal ability (clonogenicity) of U937
      cells. This synergistic effect was not eliminated by cultures containing
      neutralizing concentrations of anti-granulocyte-macrophage colony-stimulating
      factor (anti-GM-CSF), anti-interleukin 6 (anti-IL-6), anti-interferon-alpha (anti
      IFN-alpha), anti-IFN-gamma, anti-transforming growth factor-beta (anti-TGF-beta)
      serum, and anti-tumor necrosis factor-alpha (anti-TNF-alpha) serum. The
      coexistence of IL-4 and G-CSF was required for at least 48 h to reveal the
      synergistic action as assessed by preincubation and delayed addition experiments.
      Combinations of IL-4 and G-CSF showed a significant increase in CD11b expression
      on U937 cells. This action was not observed with HL60, K562, ML-1, or KG-1
      leukemic cell lines, and IL-4 did not show any synergistic suppression of
      clonogenicity of U937 leukemic cells in combination with other cytokines tested
      in this study. These results suggest that IL-4 in combination with G-CSF may have
      some capacity to synergistically suppress human leukemic cells of specific types
      with loss of clonogenicity.

PMID- 1385198
TI  - Neutrophil function in normal and Chediak-Higashi syndrome cats following
      administration of recombinant canine granulocyte colony-stimulating factor.
AB  - The effects of recombinant canine granulocyte colony-stimulating factor (rcG-CSF)
      on leukocyte counts and neutrophil function in clinically normal cats and in cats
      heterozygotic and homozygotic for Chediak-Higashi syndrome (CHS) were examined.
      CHS is a genetic disease characterized by neutropenic episodes and defects in a
      variety of phagocyte functions. Short-term administration of rcG-CSF at 10
      micrograms/kg body weight resulted in a five- to tenfold increase in circulating
      granulocytes by day 10 of administration and normalizes CHS neutrophil counts by
      day 3. The drug was specific for neutrophils as determined by differential cell
      counts. Neutrophil chemotaxis under agarose and phagocytosis of Escherichia coli
      were characterized following administration of rcG-CSF in vivo. Granulocytes
      elicited by rcG-CSF show enhanced chemotactic abilities toward activated serum,
      increased spontaneous migration, and an enhanced ability to ingest opsonized E.
      coli. At a concentration of 1 nM rcG-CSF in vitro, chemotaxis and spontaneous
      migration were increased, with no effect on phagocytosis. CHS neutrophil function
      was improved by administration of rcG-CSF in all parameters studied, although the
      defect in chemotaxis was present throughout the treatment period. We conclude
      from this study that neutrophils elicited by rcG-CSF are functionally enhanced
      and that rcG-CSF may be a viable therapy for CHS and other related disorders.

PMID- 1385199
TI  - Descending projections from the subparafascicular thalamic nucleus to the lower
      brain stem in the rat.
AB  - In the course of our study on the neuronal connections of the subparafascicular
      nucleus (SPF) in the rat, descending projections from the SPF to the lower brain
      stem were examined by using the anterograde tracer PHA-L (Phaseolus vulgaris
      leukoagglutinin) and retrograde tracer WGA-HRP (horseradish peroxidase conjugated
      to wheat germ agglutinin). When PHA-L was injected into the magnocellular and/or
      parvicellular division of the SPF (SPFm and/or SPFp), presumed terminal labeling
      was seen, bilaterally with an ipsilateral dominance, in the mesencephalic and
      pontine central gray matter, peripheral shell regions of the inferior colliculus,
      cuneiform nucleus, and superior olivary complex (mainly in the superior
      paraolivary nucleus, and additionally in the nuclei of the trapezoid body). A few
      labeled axon terminals were also seen in the cochlear nuclei bilaterally with a
      contralateral dominance. In the second set of experiments, WGA-HRP was injected
      into the inferior colliculus, superior olivary complex, or cochlear nuclei. When
      WGA-HRP was injected into the peripheral shell regions of the inferior colliculus
      or the superior olivary complex, many labeled neuronal cell bodies were seen in
      the SPFm bilaterally with an ipsilateral dominance, and a moderate number of
      labeled neuronal cell bodies were observed in the SPFp (lateral SPF) bilaterally
      with an ipsilateral dominance. When WGA-HRP was injected into the cochlear
      nuclei, a moderate number of labeled neuronal cell bodies were observed in the
      SPFm and SPFp bilaterally with a contralateral dominance. The results indicate
      that the SPFm and SPFp (lateral SPF) of the rat send a considerable number of
      projection fibers to the lower brain stem. The target regions of these projection
      fibers include the auditory relay nuclei, such as the inferior colliculus,
      superior olivary complex, and cochlear nuclei.

PMID- 1385200
TI  - Axonal and dendritic arborization of an intracellularly labeled chandelier cell
      in the CA1 region of rat hippocampus.
AB  - During the course of an in vivo intracellular labeling study, a chandelier (axo
      axonic) cell was completely filled with biocytin in the CA1 region of the
      hippocampus. Chandelier cells are known to provide GABAergic terminals
      exclusively to the axon initial segment of pyramidal cells. The lateral extent
      and laminar distribution of the dendritic arborization of the chandelier cell was
      very similar to that of pyramidal cells; the numerous basal and apical dendrites
      reached the ventricular surface and the hippocampal fissure, respectively. The
      dendrites, however, had very few spines. The neuron had an asymmetric axonal
      arbor occupying an elliptical area of 600 by 850 microns in the pyramidal cell
      layer and stratum oriens, with over three-quarters of the axon projecting to the
      fimbrial side of the neuron. Counting all clusters of terminals, representing
      individually innervated axon initial segments, the chandelier cell was estimated
      to contact 1214 pyramidal cells, a number that exceeds previous estimations,
      based on Golgi studies, by several-fold. The findings support the view that
      chandelier cells may control the threshold and/or synchronize large populations
      of principal cells.

PMID- 1385201
TI  - The reaction of mesencephalic trigeminal neurons to peripheral nerve transection
      in the adult rat.
AB  - The effects of peripheral nerve transection on mesencephalic trigeminal (MeV)
      neurons have been studied qualitatively and quantitatively in the rat. In the
      qualitative part of the study the brain stem was studied in Fink-Heimer stained
      sections 3-30 days after a masseteric nerve transection. Degeneration
      argyrophilia was observed both in the MeV tract and in the supratrigeminal and
      trigeminal motor nuclei, as well as in the lateral part of the brain stem
      reticular formation. The first signs of transganglionic degeneration (TGD) were
      seen 7 days postoperatively, and the amount of degeneration increased
      considerably with longer survival times. A quantitative analysis of the MeV
      nucleus was made 60 days after transection of the left masseteric nerve. This
      analysis showed a 10.5-22.7% reduction of cells on the side that had undergone
      masseteric nerve transection. The mean difference (left vs right side) was -2.4%
      in animals that had not been operated on. These findings show that mesencephalic
      trigeminal neurons with proprioceptive functions are very sensitive to peripheral
      nerve injury with a substantial cell loss and TGD as the result.

PMID- 1385202
TI  - Disconnected optic axons persist in the visual pathway during regeneration of the
      retino-tectal projection in the frog.
AB  - In this study, we crushed one optic nerve in the frog Litoria (Hyla) moorei and
      at intervals thereafter anterogradely labelled optic axons with horseradish
      peroxidase (HRP). For one series, HRP was applied between the eye and the crush
      site and in a second series between the crush site and the chiasm. A tectal
      projection of regenerating axons was seen in both series but, in addition, up to
      12 weeks post-crush, the second series displayed an additional projection. Its
      appearance matched that of the disconnected, but persisting, optic axon terminals
      which are found after enucleation or optic nerve ligation. We conclude that, in
      the frog, many disconnected optic axons persist throughout the period of optic
      nerve regeneration and of restoration of an orderly retino-tectal map.

PMID- 1385203
TI  - Pallidal inputs to thalamocortical neurons projecting to the supplementary motor
      area: an anterograde and retrograde double labeling study in the macaque monkey.
AB  - The relationship between thalamocortical neurons projecting to the supplementary
      motor area (SMA) and pallidothalamic projection fibers was examined with an
      anterograde and retrograde double labeling technique in macaque monkeys (Macaca
      fuscata). In each monkey, Fast Blue (FB) was injected into the hand-arm area of
      the SMA after mapping the somatotopy using intracortical microstimulation, and
      horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) was
      injected into the ipsilateral internal segment of the globus pallidus (GPi). As a
      result, numerous projection neurons labeled with FB were distributed in pallidal
      terminal areas labeled with WGA-HRP in the ventral nuclear group of the thalamus.
      The present findings indicate that the SMA receives strong indirect projections
      from the GPi via the thalamus.

PMID- 1385204
TI  - Tonic activation of locus coeruleus neurons by systemic or intracoerulear
      microinjection of an irreversible acetylcholinesterase inhibitor: increased
      discharge rate and induction of C-fos.
AB  - Recent studies in this laboratory have demonstrated that intramuscular injection
      of the irreversible acetylcholinesterase (AChE) inhibitor, soman
      (pinacolylmethylphosphonofluoridate), produces a rapid (1-2 h) and profound
      depletion (70% of control) of norepinephrine (NE) in the olfactory bulb and
      forebrain. NE is decreased only in convulsing animals. As NE-containing locus
      coeruleus (LC) neurons provide the only NE input to the olfactory bulb and the
      major NE innervation of the forebrain, the reduction of NE suggests that soman
      may cause tonic activation of LC neurons leading to rapid depletion of NE.
      Activation of LC may result from: (i) facilitation of cholinergic transmission in
      LC; (ii) soman-induced activation of excitatory inputs to LC; or (iii)
      generalized activation of LC neurons due to seizures. The present experiments
      were designed to assess these alternatives. We examined whether LC neuronal
      activity, c-fos expression, and AChE staining are altered after peripheral
      (systemic) or direct intracoerulear injection of soman in anesthetized rats. Both
      modes of soman administration rapidly and potently increase the spontaneous
      discharge rate of LC neurons. This activation was associated with a
      desynchronization of the electroencephalogram, but not with seizures. The
      discharge of LC neurons remained elevated at all postsoman intervals examined (up
      to 2 h) and was rapidly and completely reversed by systemic injection of the
      muscarinic receptor antagonist scopolamine hydrochloride, but not by the
      nicotinic receptor antagonist mecamylamine. Both systemic and intracoerulear
      soman administration completely inhibited AChE staining in LC and rapidly induced
      the expression of c-fos in LC neurons. These results demonstrate that soman
      potently and tonically activates LC neurons. This effect appears to be mediated
      by direct inhibition of AChE in LC leading to a rapid accumulation of ACh.
      Unhydrolyzed ACh tonically activates LC neurons via muscarinic receptors. Soman
      induced activation of LC neurons does not require seizures. We conclude that
      depletion of forebrain and olfactory bulb NE after systemic administration of
      soman results from tonic hypercholinergic stimulation of LC.

PMID- 1385205
TI  - Herpes simplex virus infection induces a selective increase in the proportion of
      galanin-positive neurons in mouse sensory ganglia.
AB  - We examined the effects of herpes simplex virus type 2 (HSV-2) infection on host
      neuropeptide content in mouse dorsal root ganglia (DRG) neurons following
      unilateral hind footpad inoculation. At selected survival times following
      infection, adjacent tissue sections of decalcified spine containing the paired
      4th and 5th lumbar DRGs were immunoreacted to detect HSV-2, calcitonin gene
      related peptide (CGRP), or galanin antigen. Labeled and unlabeled neurons were
      counted and the somal areas for all neurons in the infected and the contralateral
      uninfected DRG in each mouse were compared. HSV-positive neurons were small. HSV
      2 antigen was present in neurons at Day 5; by Day 14 the antigen had disappeared.
      Galanin positivity was first seen at Day 8, peaked at Day 14, gradually declined
      on Days 21 and 28, and returned to control values by Day 42. The mean soma size
      of the labeled population was small. Galanin antigen was not seen in DRG at any
      time following sham inoculation. At all times after infection, equal numbers of
      CGRP-positive neurons were seen in infected and uninfected ganglia and in sham
      operated mice. These results show that HSV-2 infection differentially affects
      host neuropeptide production and that nervous system effects are not restricted
      to the acute stage of infection. These events are consistent with those seen in
      other injury/regeneration paradigms.

PMID- 1385206
TI  - An experimental painful peripheral neuropathy due to nerve constriction. I.
      Axonal pathology in the sciatic nerve.
AB  - A constriction injury to the sciatic nerve of the rat produces a painful
      peripheral neuropathy that is similar to the conditions seen in man. The
      pathology of the sciatic nerve in these animals was examined at 10 days
      postinjury, when the abnormal pain sensations are near maximal severity. The
      nerves were examined with (1) complete series of silver-stained longitudinal
      sections of pieces of the nerve (3 cm or more) that contained the constriction
      injury in the center, (2) toluidine blue-stained semithin sections taken at least
      1 cm proximal and 1 cm distal to the constriction, and (3) EM sections taken
      adjacent to those stained with toluidine blue. One centimeter or more proximal to
      the constriction, both myelinated and unmyelinated axons were all normal. Nearer
      to the constriction, extensive degeneration of myelinated axons became
      increasingly common, as did signs of endoneurial edema. Distal to the
      constriction, the nerve was uniformly edematous and full of myelinic
      degeneration. There was a profound loss of large myelinated axons and a
      distinctly less severe loss of small myelinated and unmyelinated axons. These
      observations show that at 10 days postinjury the constriction produces a partial
      and differential deafferentation of the sciatic nerve's territory. The absence of
      degeneration in the nerve 1 cm proximal to the constriction indicates the
      survival of the primary afferent neurons whose axons are interrupted.

PMID- 1385207
TI  - Plasmodium falciparum: cytoadherence of malaria-infected erythrocytes to human
      brain capillary and umbilical vein endothelial cells--a comparative study of
      adhesive ligands.
AB  - The cytoadherence of Plasmodium falciparum-infected erythrocytes (FCR-3 line) to
      human brain capillary endothelial cells (HBEC), C32 amelanotic melanoma cells,
      and human umbilical vein endothelial cells (HUVEC) was studied. The adhesion of
      infected red cells was HBEC > amelanotic melanoma > HUVEC. The presence or
      absence of the adhesive ligands ICAM-1 (CD54 or intercellular adhesion molecule
      1), ICAM-2, and CD36 (= glycoprotein IV) was determined for each of these cells
      by indirect immunofluorescence using the monoclonal antibodies RR1/1, 6D5, and
      OKM 5/OKM 8, respectively. It appeared that a major ligand for the FCR-3 line of
      P. falciparum with amelanotic melanoma cells and HBECs was CD36. Binding to
      HUVECs was very low, presumably due to their lack of expression of CD36. HBECs,
      because of their ease of in vitro propagation, long-term maintenance of
      cytoadherent properties, and their high degree of adhesiveness, will be useful
      for in vitro studies of adherence.

PMID- 1385208
TI  - Immunologic characterization of jird lymphocyte responsiveness to Brugia pahangi
      ribosomal protein S13.
AB  - Ribosomal protein S13 of the nematode Brugia pahangi is recognized by B and T
      cells from parasite-infected animals. To identify helper T cell sites on the
      protein, 15 overlapping synthetic peptides spanning the entire molecule (Bp17.4)
      were tested for their ability to stimulate lymph node and spleen cells of peptide
      immunized and recombinant antigen-immunized jirds. Lymph node cells from animals
      immunized with peptides 6, 8, 9, 13, and 14, corresponding to Bp17.4 amino acids
      (AA) 50-70, 70-90, 80-100, 120-140, and 130-150, respectively, showed strong and
      specific responses to the homologous peptide, while only those lymph node cells
      from jirds immunized with peptides 8, 9, 13, and 14 proliferated in response to
      Bp17.4. These results suggest the existence of at least two T cell epitopes.
      Lymph node cells from infected jirds also responded to these peptides and to
      Bp17.4 (80,000 cpm). In contrast to the lymph node cells, spleen cells from
      microfilaria-positive animals failed to mount significant responses to any of the
      peptides or to Bp17.4. Splenic T cell responsiveness was restored upon removal of
      nylon wool adherent cells, suggesting active regulation of Bp17.4 reactivity. In
      liquid-phase competitive inhibition immunoassays, peptides 1 (AA 1-30) and 6 (50
      70) blocked antibody binding and, therefore, these regions contain conformational
      antibody-binding sites. This model system should prove useful for analyzing
      regulation of epitope-specific responses in experimental filariasis.

PMID- 1385209
TI  - More on pathogenesis and treatment of septic shock.

PMID- 1385210
TI  - Bovine alpha 2-antiplasmin. N-terminal and reactive site sequence.
AB  - Bovine alpha 2-antiplasmin (alpha 2AP) has been purified and partially
      characterized. The amino acid composition is very similar to that of human alpha
      2AP, and the N-terminal (23 residues determined) and reactive site loop sequences
      (42 residues determined) are highly homologous to those of the human protein.
      Compared with human alpha 2AP, bovine alpha 2AP has an 18-residue N-terminal
      extension, homologous with part of the pre-sequence of human alpha 2AP. A re
      investigation of the N-terminal sequence of freshly prepared human alpha 2AP
      reveals a new form extended by 12 residues.

PMID- 1385211
TI  - Differential expression of keratan sulphate proteoglycans fibromodulin, lumican
      and aggrecan in normal and fibrotic rat liver.
AB  - In this study we investigated in rat liver the expression of genes coding for the
      core proteins of fibromodulin, lumican and aggrecan. By means of Northern
      analysis and in situ hybridization we present evidence for their differential
      transcription during liver fibrogenesis. Whereas no fibromodulin expression could
      been detected, both lumican and aggrecan transcripts were found displaying
      different time-courses of expression during the fibrogenic process. Based on
      studies performed in non-hepatic tissues, these proteoglycans are considered to
      have keratan sulphate glycosaminoglycan side chains. The expression of the
      respective core protein genes in liver is unexpected since published data have
      shown neither keratan sulphate nor its synthesis de novo in this tissue. The
      results also point to a putative role of aggrecan in the modulation of the
      inflammatory process in the liver.

PMID- 1385212
TI  - Cloning and sequencing of a rat type II activin receptor.
AB  - A full-length cDNA for a rat type II activin receptor was cloned by hybridization
      from a rat ovary cDNA library. The deduced amino acid sequence (513 residues)
      containing a single membrane-spanning domain and an intracellular kinase domain
      with predicted serine/threonine specificity. The amino acid sequence is 99.8% and
      99.4% identical in the coding region with the previously cloned mouse and human
      type II activin receptor, and only 66.7% identical in the coding region with the
      previously cloned rat type IIB activin receptor. We examined the effect of PMSG
      hCG on the mRNA level of type II activin receptor in immature rat ovaries.
      Northern blot analysis of ovarian RNA revealed two mRNAs (3.0 kb and 6.0 kb).

PMID- 1385213
TI  - Altered protein folding may be the molecular basis of most cases of cystic
      fibrosis.
AB  - Experiments have demonstrated that the cystic fibrosis transmembrane conductance
      regulator protein (CFTR), containing the most common cystic fibrosis (CF)-causing
      mutation (delta F508), reaches the plasma membrane in reduced amounts. Studies of
      a peptide model of CFTR indicate that the delta F508 mutated region is more
      sensitive to denaturating conditions. This paper proposes that altered protein
      folding accounts for these findings, and, thus, most cases of CF. Significantly,
      the hypothesis makes specific predictions about the effect of stabilizing
      conditions on mutant CFTR, and, further, suggests a new class of pharmaceuticals
      that may prove effective in the treatment of this important genetic disease.

PMID- 1385214
TI  - Expression of retinoic acid nuclear receptors in the mouse embryonal carcinoma
      cell line PCC7-Mz1.
AB  - Mouse embryonal carcinoma cell line PCC7-Mz1 can serve as a model of mammalian
      neural development [1989, J. Cell. Biol. 109, 2481-2493]. Upon exposure to all
      trans retinoic acid (RA), Mz1 cells differentiate into a stable pattern of
      neurons, astroglia and fibroblasts whereas variants of the parental cell line
      either are restricted in their patterns of derivatives or do not respond at all
      to RA. Using gene probes specific for the alpha 1, alpha 2 and beta 2 isoforms of
      the retinoic acid nuclear receptor, we have studied by Northern blot analysis the
      expression of these transcription factors in uninduced and induced cells of clone
      Mz1 and in variants with different developmental potential. alpha 1-RAR is
      expressed constitutively in all variants independent of whether RA is present or
      not. Soon after addition of 10(-7) M RA, alpha 2-RAR is induced in RA-responsive
      cells reaching within a few hours a plateau level that remains unchanged
      throughout the developmental process. In contrast, the beta 2 isoform is
      expressed only transiently after RA-induction despite the continuous presence of
      RA. Other RAR isoforms are expressed only in trace amounts.

PMID- 1385216
TI  - The NK1 receptor is involved in the neurokinin-induced shape change of rabbit
      platelets.
AB  - Substance P and selective neurokinin receptor agonists have been tested for their
      ability to induce shape change in rabbit platelets. Substance P and the NK1
      receptor agonist Ac [Arg6,Sar9,Met(O2)11]-substance P (6-11) induced shape change
      (EC50 = 3 and 6 nM, respectively), whereas the selective NK2 agonist [Nle10]
      Neurokinin A (4-10) and the selective NK3 agonist [MePhe7]-Neurokinin B did not
      show any effect. Moreover, the specific NK1 receptor antagonist CP-96,345
      selectively and dose-dependently counteracted the effect of substance P or of the
      NK1 receptor agonist (IC50 = 2 and 0.8 nM, respectively), whereas the selective
      NK2 receptor antagonist, SR 48968, had no effect. Unlike for serotonin or low
      doses of ADP, epinephrine did not allow substance P or the NK1 receptor agonist
      to become a proaggregating substance. These data therefore show that the NK1
      receptor is solely involved in the neurokinin-induced shape change of rabbit
      platelets.

PMID- 1385215
TI  - Effect of heat-shock on Plasmodium falciparum viability, growth and expression of
      the heat-shock protein 'PFHSP70-I' gene.
AB  - Cultures of the human malaria parasite Plasmodium falciparum were subjected to
      heat-shock for varying times and temperatures and then tested for their
      viability, growth and expression of heat-shock protein. Results show that the
      majority of parasites remained viable after heat-shock but their growth was
      affected. However, the expression of the heat-shock protein 'PFHSP70-I' gene was
      enhanced after heat-shock. We conclude that malarial parasites are able to
      survive in vivo during fever probably due to the overexpression of the heat-shock
      protein gene.

PMID- 1385217
TI  - Human immunodeficiency virus type 1 reverse transcriptase. Affinity labeling of
      the primer binding site.
AB  - Affinity modification of the primer site of HIV1-RT was performed with an
      oligonucleotide derivative containing a photoreactive azido group at the 5' end
      of d(pT)10. The affinity of HIV1-RT for d(pT)10 and for its derivative was first
      estimated by measuring the Michaelis constants of these two oligonucleotides
      acting as primers in the retrotranscription of poly(rA). The enzyme was then
      inactivated under UV-irradiation at 303-365 nm in the presence of ArN3-d(U*T9);
      the dependence of the rate of inactivation on primer concentration was found to
      be consistent with the Km value. Last, selectivity of affinity modification was
      demonstrated through elongation of the covalently bound primer and selective
      protection of inactivation by d(pT)10 or tRNA(Lys).

PMID- 1385219
TI  - A slow anion channel in guard cells, activating at large hyperpolarization, may
      be principal for stomatal closing.
AB  - Slowly activating anion channel currents were discovered at micromolar
      'cytoplasmic' Ca2+ during patch-clamp measurements on guard-cell protoplasts of
      Vicia faba and Xanthium strumarium. They activated at potentials as low as -200
      mV, with time constants between 5 and 60 s, and no inactivation. The broad
      voltage dependence exhibited a current maximum near -40 mV. The single-channel
      open time was in the order of seconds, and the unitary conductance was 33 ps,
      similar to that of the already described 'quick' anion channel of guard cells.
      Because of its activity at low potentials, the slow anion channel may be
      essential for the depolarization of the plasmalemma that is required for salt
      efflux during stomatal closing.

PMID- 1385218
TI  - Identification of an ion channel-forming motif in the primary structure of
      tetanus and botulinum neurotoxins.
AB  - Synthetic peptides with amino acid sequences corresponding to predicted
      transmembrane segments of tetanus toxin were used as probes to identify a channel
      forming motif. A peptide denoted TeTx II, with sequence GVVLLLEYIPEITLPVIAALSIA,
      forms cation-selective channels when reconstituted in planar lipid bilayers. The
      single channel conductance in 0.5 M NaCl or KCl is 28 +/- 3 and 24 +/- 2 pS,
      respectively. In contrast, a peptide with sequence NFIGALETTGVVLLLEYIPEIT,
      denoted as TeTx I, or a peptide with the same amino acid composition as TeTx II
      but with a randomized sequence, do not form channels. Conformational energy
      calculations show that a bundle of four amphipathic alpha-helices is a plausible
      structural motif underlying observable pore properties. The identified functional
      module may account for the channel-forming activity of both tetanus toxin and the
      homologous botulinum toxin A.

PMID- 1385220
TI  - Cloning and expression of the epsilon 4 subunit of the NMDA receptor channel.
AB  - The primary structure of a novel subunit of the mouse NMDA (N-methyl-D-aspartate)
      receptor channel, designated epsilon 4, has been revealed by cloning and
      sequencing the cDNA. The epsilon 4 subunit shares high amino acid sequence
      identity with the epsilon 1, epsilon 2 and epsilon 3 subunits of the mouse NMDA
      receptor channel, thus constituting the epsilon subfamily of the glutamate
      receptor channel. Expression from cloned cDNAs of the epsilon 4 subunit together
      with the zeta 1 subunit in Xenopus oocytes yields functional NMDA receptor
      channels. The epsilon 4/zeta 1 heteromeric channel exhibits high apparent
      affinities for agonists and low sensitivities to competitive antagonists. The
      epsilon 4 subunit is thus distinct in functional properties from the epsilon 1,
      epsilon 2 and epsilon 3 subunits, and contributes further diversity of the NMDA
      receptor channel.

PMID- 1385221
TI  - Osteoclasts express high levels of p60c-src, preferentially on ruffled border
      membranes.
AB  - Expression of p60c-src, the normal cellular counterpart of the transforming
      protein of Rous sarcoma virus (RSV), p60v-src, was examined in mouse and rat
      authentic osteoclasts and mouse osteoclast-like multinucleated cells (MNCs)
      formed in vitro. In co-cultures of mouse osteoblastic cells and spleen cells, the
      expression of p60c-src strikingly increased on day 5 in parallel with the
      appearance of MNCs in the presence of 1 alpha,25-dihydroxyvitamin D3 (1
      alpha,25(OH)2D3). Immunohistochemical examination confirmed the high level
      expression of p60c-src in both mouse authentic osteoclasts and MNCs. Electron
      microscopic examination revealed that p60c-src was primarily localized on ruffled
      border membranes and vacuoles, but not on the clear zone in rat authentic
      osteoclasts. These results suggest that p60c-src is important in osteoclastic
      bone resorption.

PMID- 1385222
TI  - Expression of a functional alpha-macroglobulin receptor binding domain in
      Escherichia coli.
AB  - We have expressed receptor-binding domains of human alpha 2-macroglobulin and rat
      alpha 1-macroglobulin in Escherichia coli. Expression levels of both recombinants
      were quite high, but the human one was insoluble, probably forming inclusion
      bodies. The rat domain, which lacks the human disulfide, was produced in a
      soluble form and readily purified by two simple chromatographic steps. Purified
      recombinant rat alpha 1-macroglobulin receptor-binding domain was fully
      functional in binding to the alpha-macroglobulin receptor on human fibroblasts.
      This 142 residue domain should serve as an excellent template for analyzing the
      structural requirements for alpha-macroglobulin receptor ligation and dissecting
      the varied biological functions resulting from such ligation.

PMID- 1385223
TI  - Selective expression of a progesterone receptor on the human sperm surface.
AB  - OBJECTIVE: To visualize progesterone (P) binding sites on the sperm surface,
      examine the relationship between hormone binding and hormone action (acrosome
      reaction), and determine the size of the hormone-responsive sperm subpopulation.
      DESIGN: Kinetic analysis of P binding was combined with the assessment of the
      hormone effect using a fluorescent acrosomal marker. SETTING: Private hospital,
      medical research center, and a university-based andrological laboratory.
      PATIENTS, PARTICIPANTS: Sperm samples were from healthy volunteers with normal
      spermiogram values. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Progesterone
      binding was analyzed by fluorescence microscopy and flow cytometry using P
      coupled to fluorescein isothiocyanate-labeled bovine serum albumin.
      Tetramethylrhodamine isothiocyanate-labeled Pisum sativum agglutinin was used as
      acrosomal marker in double-labeling experiments. RESULTS: After in vitro
      capacitation, only few spermatozoa (approximately 10%) were able to bind P to the
      cell surface, but most of these cells subsequently generated the acrosome
      reaction in response to hormone binding. CONCLUSIONS: The expression of P
      receptor sites on the human sperm surface is a major factor controlling the P
      induced acrosome reaction. Further studies are warranted to explore if defective
      expression of the receptor can compromise fertility.

PMID- 1385224
TI  - Massive air embolism--a possible cause of death after operative hysteroscopy
      using a 32% dextran-70 pump.
AB  - Although considered a safe procedure, operative hysteroscopy has been reported to
      result in serious and even fatal complications. A fatal outcome is described
      after operative hysteroscopy. The attending team made a diagnosis of massive air
      embolism. However, HBO therapy, which is the specific treatment for air embolism,
      yielded only transient improvement. The pathologist's diagnosis on autopsy was
      anaphylaxis. These two complications must be borne in mind during the procedure,
      and a contingency plan developed for dealing with them should they arise.

PMID- 1385225
TI  - Identification of restriction-fragment length polymorphisms for the human
      chorionic gonadotropin-beta/luteinizing hormone-beta gene cluster.
AB  - OBJECTIVE: To determine whether restriction fragment length polymorphisms are
      present using a deoxyribonucleic acid (DNA) probe for human luteinizing hormone
      beta subunit (hLH-beta). If the gene for hLH-beta is polymorphic, genetic
      diagnosis of disorders of luteinizing hormone (hLH) and human chorionic
      gonadotropin (hCG) production could become possible. DESIGN: Study of genomic DNA
      from controls with a variety of restriction enzymes to identify polymorphisms.
      SETTING: Laboratories of the Department of Obstetrics and Gynecology, Department
      of Oral Biology, Medical College of Georgia, Augusta, Georgia. PATIENTS:
      Unrelated control men and women seen in clinics at the Medical College of
      Georgia. INTERVENTIONS: Genomic DNA was extracted from patients and digested with
      eight different restriction enzymes for the study of the hLH-beta gene by
      Southern analysis. MAIN OUTCOME MEASURE: Fragment (band) sizes on radiographs
      from Southern blots were compared with those from molecular weight standards.
      CONCLUSIONS: Restriction fragment length polymorphisms were identified for four
      of the restriction enzymes, DraI, HincII, MboI, and KpnI. These polymorphisms may
      be useful in the diagnosis of disorders of hLH and hCG production.

PMID- 1385226
TI  - Absence of autoantibodies to human chorionic gonadotropin in women with a history
      of habitual abortion.
AB  - OBJECTIVE: To determine if immunization to human chorionic gonadotropin (hCG) has
      occurred in women with habitual abortion. DESIGN: Comparisons between nonpregnant
      patients with a history of at least three consecutive miscarriages (n = 48) and
      normal controls (n = 38). In addition, 28 habitual aborters were compared, while
      pregnant, with 37 pregnant control women. Antibodies to hCG were assessed by a
      solid-phase immunometric assay using europium-labeled antihuman immunoglobulin
      (Ig)G as tracer; this method is capable of detecting antibodies toward hCG in
      serum of patients immunized with beta-hCG-tetanus toxoid conjugate. SETTING:
      Departments I and II of Obstetrics and Gynecology, University Central Hospital of
      Helsinki, Helsinki, Finland. RESULTS: Three patients (1 primary and 2 secondary
      aborters, 1 both while pregnant and not pregnant) showed evidence of Ig binding
      to hCG, but the binding was not inhibited by an excess of hCG. CONCLUSIONS:
      Antibodies against endogenous hCG may not be responsible for habitual abortion.

PMID- 1385227
TI  - [Nature as a model. Aids to learning about tooth forms].

PMID- 1385228
TI  - Insulin-like growth factor binding protein-1 in female reproductive functions.
AB  - Multiple lines of evidence suggest that growth factors and related proteins are
      involved in the regulation of reproductive functions. It appears that hormones
      and local regulators control each other's production and action. Thus, the same
      regulatory factor may have different effects depending on the context in which it
      acts. Insulin-like growth factor-binding protein-1 (IGEBP-1) is a member of the
      family of soluble proteins that bind insulin-like growth factors (IGF-I and IGF
      II) and modulate their biological actions at the cellular level. In the
      reproductive tract, endometrium and ovarian granulosa-luteal cells express IGFBP
      1 mRNA and secrete the protein at a certain stage of differentiation. During
      pregnancy, IGFBP-1 is a major secretory product of decidualized endometrium. This
      report summarizes the current views on IGFBP-1 with special regard to its
      synthesis, regulation and potential role in female reproductive tissues.

PMID- 1385229
TI  - Cardiac arrest from intracavitary dextran.

PMID- 1385230
TI  - Sidechain-ion interactions in ion channels: a molecular modelling study.

PMID- 1385231
TI  - Synthesis of glycosyl-phosphatidyl-inositol lipids by a cell-free system prepared
      from asexual erythrocytic stages of the malaria parasite Plasmodium falciparum.

PMID- 1385232
TI  - Ribozymes acting against the transcription factor Pit-1.

PMID- 1385233
TI  - Water, ions and membrane proteins: how would Darwin look at cytochromes and
      channels?

PMID- 1385234
TI  - 2',3'-cyclic nucleotide-3'-phosphohydrolase and signal transduction in central
      nervous system myelin.

PMID- 1385235
TI  - Medial edge epithelium fate traced by cell lineage analysis during epithelial
      mesenchymal transformation in vivo.
AB  - Vital cell labeling techniques were used to trace the fate of the medial edge
      epithelial (MEE) cells during palatal fusion in vivo. Mouse palatal tissues were
      labeled in utero with DiI. The fetuses continued to develop in utero and tissues
      of the secondary palate were examined at several later stages of palatal
      ontogeny. The presence and distribution of DiI was correlated with the presence
      of cell phenotype-specific markers. During the initial stages of palatal fusion
      the DiI-labeled MEE were present in the midline position. These cells were
      attached to an intact laminin-containing basement membrane and contained keratin
      intermediate filaments. At later stages of palatogenesis the DiI-labeled MEE were
      not separated from the mesenchyme by an intact basement membrane and did not
      contain keratin. In late fetal development, DiI-labeled cells without an
      epithelial morphology were present in the mesenchyme. The transition of the DiI
      labeled cells from an epithelial phenotype to a mesenchymal phenotype is
      consistent with a fate of epithelial-mesenchymal transformation rather than
      programmed cell death.

PMID- 1385237
TI  - Immunomodulatory properties of soluble recombinant human CD58 (LFA-3) molecules.
AB  - The interaction between the E-rosette receptor (CD2) expressed on the cell
      surface of T lymphocytes and its natural ligand CD58 (LFA-3), a broadly
      distributed cell surface molecule, represents a potential target for immune
      modulation. To explore this possibility, we have expressed a soluble recombinant
      form of human CD58 which exerts potent biological effects in that it acts as a
      competitive inhibitor for cell surface CD58 in its binding to CD2 positive
      lymphocytes. Thus, recombinant CD58 blocks NK-mediated cytotoxicity, the mixed
      lymphocyte reaction, and the T lymphocyte adhesion to CD58 positive cells. In
      contrast, recombinant CD58 synergized with mitogenic CD2R monoclonal antibodies
      (anti-T11(2/3) or 9.1) in T cell triggering.

PMID- 1385236
TI  - Ribosomes as carriers for antigenic determinants of the surface of micro
      organisms.
AB  - Over the past twenty-five years, many authors have reported evidence of the
      immunoprotective capacity of ribosomes isolated from bacteria, fungi and
      parasites. Since 1971 we have explored the protective capacity of ribosomes
      isolated from a large variety of micro-organisms responsible for human and animal
      diseases. Accurate biochemical characterization of ribosomes always reveals trace
      amounts of non-ribosomal components such as short polysaccharides strongly linked
      to ribosomal RNA after phenol extraction even under denaturing conditions. rRNA
      antigen complexes have been purified from Klebsiella pneumoniae ribosomes
      inducing high level of protection against homologous experimental infection in
      mice. Monoclonal antibodies raised against ribosomes and then selected for their
      ability to confer passive immunity to mice have been used to study the mechanism
      of the protection induced by ribosomes and to characterize their "immunogenic
      principle". These investigations have clearly shown the presence on ribosomes of
      epitopes corresponding to antigens normally exposed on the membrane of the
      bacteria. In the original concept of "ribosomal immunotherapy" that we have
      developed, ribosomes can be considered as natural carriers for cell surface
      epitopes, presenting them to the immune system in a highly immunogenic
      configuration.

PMID- 1385238
TI  - Monoclonal antibody MT2 identifies an extracellular matrix glycoprotein that is
      co-localized with tenascin during adult newt limb regeneration.
AB  - Using immunohistochemical techniques and mAb MT2, we describe here a novel
      extracellular matrix (ECM) molecule that is developmentally regulated during limb
      regeneration in adult newts. The MT2 antigen appears during preblastema stages,
      is most abundant during blastema stages, and persists, near undifferentiated
      cells, until digit stages. The MT2 antigen is located in an acellular layer under
      the wound epithelium and throughout the ECM of the undifferentiated mesenchyme as
      a thick, cord-like component. In unamputated limbs mAb MT2 reactivity is
      restricted to tendons, myotendinous junctions, periosteum and to a layer of
      material beneath the epidermis. In both unamputated limbs and regenerating limbs,
      the reactivity to mAb MT2 colocalizes closely with urodele tenascin. Immunoblot
      analysis of blastema extracts showed that the unreduced form of the MT2 antigen
      is a large, polydispersed protein of approximately the same size as tenascin.
      However, based upon (a) molecular weights of reduced subunits, (b) competition
      experiments on tissue sections, and (c) analysis of molecules immunoprecipitated
      by mAb MT2, we conclude that the MT2 substance is unrelated biochemically to
      tenascin. The results from immunoblots, enzyme digestions and DEAE-Sephacell
      binding studies suggest that the unreduced MT2 antigen is a large protein
      composed of subunits which are connected by disulfide bonds. Reduction of the MT2
      antigen results in three components recognized by mAb MT2. The largest of these
      reduced components is a chondroitin sulfate-like glycoprotein with a molecular
      weight (Mr) of 310-325 x 10(3). A second component (Mr, 285-300 x 10(3)) is the
      core protein of the 310-325 x 10(3) glycoprotein.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1385240
TI  - Separation of the toxic and glutathione-enhancing effects of the naturally
      occurring nitrile, cyanohydroxybutene.
AB  - Cyanohydroxybutene (CHB) is reported to be hepatotoxic in male Fischer 344 rats
      at an oral dose of 300 mg/kg and, while no longer hepatotoxic, pancreatotoxic at
      200 mg/kg. In addition, the 200 mg/kg dose causes a persistent elevation in
      hepatic and pancreatic glutathione (GSH). This study was conducted to determine
      if smaller doses of CHB could cause GSH elevation in the absence of toxicity. A
      single oral dose of 100 mg/kg or multiple lower doses (50 mg/kg daily for 3 days
      or 30 mg/kg for 6 days) caused a significant and persistent increase in
      pancreatic GSH, although hepatic levels were unchanged. Ten milligrams per
      kilogram, even daily for 24 days, was without effect on hepatic or pancreatic
      GSH. Neither a single oral dose of 100 mg/kg nor multiple lower doses were
      associated with toxicity. However, when either 100 or 50 mg/kg were administered
      intravenously, pancreatic apoptosis was observed. In animals dosed with 100 mg/kg
      iv, mixed histiocytic and suppurative inflammation and frank pancreatic necrosis
      also developed and were associated with elevated plasma lipase and amylase. The
      animals receiving CHB intravenously also exhibited elevated GSH levels in both
      pancreas and liver. This study shows that oral doses between 30 and 100 mg CHB/kg
      can be used to elevate GSH levels without any pancreatotoxicity. However, a
      single 50 mg CHB/kg dose given intravenously causes apoptosis, while 100 mg/kg
      causes severe pancreatotoxicity with necrosis.

PMID- 1385239
TI  - Structural features and sites of expression of a new murine 65 kD and 48 kD hair
      related keratin pair, associated with a special type of parakeratotic epithelial
      differentiation.
AB  - In the course of studies on local keratin phenotypes in the epidermis of the
      adult mouse, we have identified a new 65 kD and 48 kD keratin pair. In mouse
      skin, this keratin pair is only expressed in suprabasal cells of adult mouse tail
      scale epidermis which is characterized by the complete absence of a granular
      layer and the formation of a remarkably compact stratum corneum. A second site in
      which the 65 kD and 48 kD keratin pair is suprabasally expressed and whose
      morphology corresponds to that of tail scale epidermis is found in the posterior
      unit of the complex filiform papillae of mouse tongue. The causal relationship of
      the expression of the 65 kD and 48 kD keratins with this particular type of a non
      pathological epithelial parakeratosis is emphasized by the suppression of the
      mRNA synthesis of the two keratins during retinoic acid mediated orthokeratotic
      conversion of tail scale epidermis. Apart from tail scale epidermis and the
      posterior unit of the filiform papillae, the 65 kD and 48 kD keratin pair is,
      however, also coexpressed with "hard" alpha keratins in suprabulbar cells of hair
      follicles and in suprabasal cells of the central core unit of the lingual
      filiform papillae. The non alpha-helical domains of the two new keratins are rich
      in cysteine and proline residues and lack the typical subdomains into which
      epithelial keratins of both types can be divided. This structural resemblance of
      the 65 kD and 48 kD keratins to "hard" alpha keratins is supported by comparative
      flexibility predictions for their non alpha-helical domains. Phylogenetic
      investigations then show that the 65 kD and 48 kD keratin pair has evolved
      together with hair keratins, but has diverged from these during evolution to
      constitute an independent branch of a pair of hair-related keratins. In view of
      this exceptional position of the 65 kD and 48 kD keratins within the keratin
      multigene family, their expression has apparently been adopted by rare anatomical
      sites in which an orthokeratinized stratum corneum would be too soft and a hard
      keratinized structure would be too rigid to meet the functional requirement of
      the respective epithelia.

PMID- 1385241
TI  - A two-signal model for regulation of immunoglobulin isotype switching.
AB  - A characteristic feature of the humoral immune response is a switch from IgM to
      other Ig isotypes that typically occurs subsequent to a first exposure to
      antigen. Ultimately, isotype switching involves a DNA rearrangement that
      recombines a variable region gene, initially juxtaposed to the mu constant region
      gene (C mu), with a constant region gene located downstream of C mu. Isotype
      switching is controlled by T lymphocyte-derived cytokines, such as interleukin-4
      (IL-4), gamma-interferon (gamma-IFN), and TGF beta, which direct B lymphocytes to
      switch to specific Ig classes. For example, IL-4, directs murine B cells to
      produce IgG1 and IgE, and human B cells to produce IgE and IgG4. IL-4 appears to
      direct switching to IgE and IgG1 by inducing transcription of the epsilon and
      gamma 1 constant region genes before switch recombination. However, IL-4 is not a
      sufficient stimulus for isotype switching, and additional signals are required to
      complete this process. This second signal can be provided by physical contact
      with activated T cells, which may involve, at least in part, ligation of the CD40
      molecule. For murine B cells the second signal may also be provided by IL-5.
      Isotype switching in B lymphocytes may provide a useful model for directed DNA
      recombination in higher eukaryotes.

PMID- 1385242
TI  - Structural basis of antigenic specificity and design of new vaccines.
AB  - This manuscript describes the design of new vaccines based on synthetic peptides.
      To this end, we first analyze the structural basis of antigenic reactivity and
      specificity and the various types of epitopes that form the mosaics of
      macromolecular antigens, as well as the regulatory mechanisms involved in immune
      recognition. A distinction is made between sequential or continuous epitopes, and
      discontinuous or conformational ones, which are the majority of epitopes in
      globular proteins. In this context it is of particular interest to identify
      epitopes reacting with B cells and T cells, respectively, or with cytotoxic T
      cells, in association with the major histocompatibility cell-surface antigens,
      and the role of these interactions in protective immunity. Identification of such
      epitopes in proteins of viral, bacterial, or parasitic organisms led to the
      synthesis of peptides, which when used in conjunction with appropriate carriers
      and/or adjuvants induced neutralizing antibodies. Particular examples are
      described, including: bacterial epitopes and mainly those of toxins of
      diphtheria, cholera, and shigella, leading not only to neutralizing antibodies
      but also to protective immunity against the deleterious effects of the respective
      toxins; parasite epitopes, such as those leading to anti-malaria vaccine, based
      on either the sporozoite or the merozoite stage antigens; viral epitopes leading
      to protective immunity, with special emphasis on influenza virus where induction
      of CTL is crucial; and finally, synthetic peptide vaccines against HIV, which
      should lead to broad specificity protective immunity while avoiding the risks of
      a vaccine based on the infectious agent. The rapid recent progress in this field,
      as described in this review, increases the prospect of constructing successful
      synthetic peptide vaccines in the not too distant future.

PMID- 1385243
TI  - Receptor tyrosine kinase substrates: src homology domains and signal
      transduction.
AB  - Among the intracellular milieu of proteins are molecules with defined biochemical
      functions that serve as substrates for ligand-activated tyrosine kinase
      receptors. It seems likely that some of these substrate molecules are elements of
      a critical signaling pathway used by growth factors to control cell proliferation
      and subverted by oncogenes to deregulate this process. Although the process of
      cell growth and division is relatively slow compared with other hormonally
      regulated responses, homeostasis in a human being requires approximately 20 x
      10(6) cell divisions per second for the renewal of various cell populations. This
      review summarizes the present understanding of tyrosine kinase substrates that
      seem likely to have key roles in the signal transduction pathway that regulates
      cell proliferation. This includes structural features of these molecules, the
      influence of tyrosine phosphorylation on their functions, the biological roles of
      these proteins, and the capacity of these substrates to associate with activated
      receptor tyrosine kinases.

PMID- 1385244
TI  - Mechanism of bradycardia-dependent appearance of manifest extrasystoles in
      concealed bigeminy. A theoretical model derived from the concepts of longitudinal
      dissociation and multilevel block in the reentrant pathway of extrasystoles.
AB  - A case of bradycardia-dependent appearance of manifest extrasystoles in concealed
      bigeminy is presented. To explain the mechanism of such bradycardia-dependent
      appearance, a theoretical model is derived from the concepts of "longitudinal
      dissociation" and "multilevel block" in the reentrant pathway of extrasystoles.
      In the theoretical model, functional longitudinal dissociation divides the
      reentrant pathway into dual pathways F and S. When manifest extrasystoles are not
      found for a long time, alternate sinus impulses pass through both pathways F and
      S, but become concealed extrasystoles because of insufficient conduction delay in
      the pathways. The other alternate sinus impulses are blocked in the pathways; in
      pathway F, the impulses are blocked at the entrance, while in pathway S, the
      impulses are blocked at a more distal level. When sinus cycles gradually
      lengthen, one of such alternate sinus impulses passes through the entrance of
      pathway F and, traveling very slowly, is blocked at a more distal level. The next
      sinus impulse is blocked at the entrance of pathway F; namely, 3:2 Wenckebach
      block occurs at the entrance of pathway F. Thus this sinus impulse enters only
      pathway S and passes through pathway S with enough conduction delay to become a
      manifest reentrant extrasystole.

PMID- 1385245
TI  - [Extrasystole concealed between automatism and reentry].

PMID- 1385246
TI  - [Prevention of sudden death with antiarrhythmic agents after myocardial
      infarction].

PMID- 1385247
TI  - [Transfection of pancreatic acinar cells (AR4-2J) by bFGF modifies cell
      morphology and biosynthesis of pancreatic secretory enzymes].
AB  - Basic fibroblast growth factor (bFGF or FGF-2) is present in the basal membrane
      of pancreatic cells during the pancreatic embryonic development. The expression
      of bFGF receptors has been described in normal pancreatic cells. By contrast,
      pancreatic cancer cells express not only the bFGF receptors but also the bFGF
      itself. With the aim of understanding the effects induced by the production of
      bFGF by pancreatic cancer cells, the pancreatic acinar cell line (AR4-2J) was
      used. AR4-2J cells do not produce bFGF but express bFGF receptors. These cells
      were transfected with a vector containing the bFGF cDNA encoding the three
      different forms of bFGF characterized in tumor cells. Results showed that the
      bFGF expression induced important phenotypic and enzymatic modifications. The
      transfected cells lost some morphological features of the acinar cells and
      expressed amylase and lipase at low levels (a 90% decrease for amylase activity,
      whereas lipase activity was barely detectable). These results suggest that bFGF
      could be involved in maintaining pancreatic cells in a slightly differentiated
      state.

PMID- 1385248
TI  - Effects of tetragastrin on mucus glycoprotein in rat gastric mucosal protection.
AB  - The effects of tetragastrin on mucus glycoprotein (mucin) metabolism and mucosal
      protection in rat gastric mucosa were investigated. Rats were administered with
      various doses of tetragastrin (12, 120, or 400 micrograms/kg body weight; s.c.),
      followed by 50% ethanol-induced gastric injury. Tetragastrin caused a significant
      increase in mucin content in the corpus mucosa and prevented 50% ethanol-induced
      gastric mucosal damage in a dose-dependent manner. For assessment of the effects
      of tetragastrin on the metabolism of gastric mucin in detail, changes in mucin
      distribution in the three different layers of rat gastric mucosa were examined
      one hour after single administration of tetragastrin. A significant increase in
      the mucin content was noted in the mucus gel and surface mucosal layer. Mucin
      content in the deep mucosa corresponding mainly to the mucus neck cell mucin
      underwent virtually no change by this treatment. An increase in mucin in the
      mucus gel and surface mucosa would thus appear due to the administration of
      tetragastrin and may possibly be related to the protective action of the gastric
      mucosa against injury. The data demonstrate a possibility that gastrin may have
      potential for enhancing gastric mucosal protection associated with mucus
      secretion and/or mucus synthesis on the surface mucosa of rat gastric mucosa.

PMID- 1385249
TI  - Hepatitis C virus detection is facilitated by the combined use of c100 protein
      and GOR epitope.
AB  - Assay for the antibody to the c100 protein (anti-c100) lacks sensitivity in terms
      of detection of hepatitis C virus (HCV) in all samples. The author used anti-c100
      and antibody to the GOR epitope (anti-GOR) by the enzyme-linked immunosorbent
      assay to examine 524 patients with chronic liver disease and 682 volunteer blood
      donors in Fukuoka, Japan. The prevalence of HCV infection, as revealed by the
      presence of anti-c100 and/or anti-GOR, was 3.9% in 540 volunteer blood donors,
      12.7% in 142 volunteers with abnormal liver function, 7.4% in 135 patients with
      HBsAg-positive liver disease and 89.5% in 389 patients with non-A, non-B (NANB)
      liver disease. These results show a higher prevalence than demonstrated only by
      the anti-c100 in NANB liver disease patients (82.5%, P < 0.01). The concurrence
      of anti-c100 and anti-GOR in subjects with HCV infection was 23.8% in 21
      volunteer blood donors, 44.4% in 18 volunteers with abnormal liver function and
      61.2% in 348 NANB liver disease patients. The concurrence seems to increase with
      deterioration of liver function. We concluded that combination assay for anti
      c100 and anti-GOR demonstrated a more accurate prevalence of HCV infection than
      single assay for anti-c100 among NANB liver disease patients, and that the
      presence of anti-GOR plays a role in liver disease in anti-HCV-positive subjects.

PMID- 1385250
TI  - Acute reflux pancreatitis in rats: a comparison between two experimental models.
AB  - This study was undertaken in order to compare the reliability of two acute reflux
      pancreatitis models in rats, one performed by positioning a silicon tube in the
      duodenum and the other by creating a gastro-jejunal anastomosis. In two groups (A
      = 10 and B = 10 rats) a silicon tube was positioned in the duodenum; in the
      remaining two groups (C = 12 and D = 6 rats) a latero-lateral antecolic
      anisoperistaltic gastro-jejunal anastomosis was performed 30 days before surgery.
      A closed duodenal loop was created for 12 hours in groups A and C but not in B
      and D. Rats in both groups A and C developed acute pancreatic inflammation of a
      mild degree. Sham operated rats with silicon tube placement had higher
      histological damage scores than those with gastro-jejunal anastomosis. The
      difference found between the two groups of rats which underwent gastro-jejunal
      anastomosis was more marked than that between the two groups which had silicon
      tube placement. It was concluded that the creation of a gastro-jejunal
      anastomosis is probably the safer procedure to allow gastro-intestinal flow in
      acute reflux pancreatitis in rats.

PMID- 1385251
TI  - Alpha-fetoprotein producing carcinoma of the gallbladder associated with
      anomalous arrangement of the pancreaticobiliary ductal system--early detection
      through an attack of acute pancreatitis.
AB  - A 56-year-old female was admitted to our hospital with a diagnosis of acute
      pancreatitis. Ultrasonography revealed a hypoechoic tumor in the gallbladder. The
      serum alpha-fetoprotein (AFP) level was 971 ng/ml. After healing of the acute
      pancreatitis, the anomalous arrangement of the pancreaticobiliary ductal system
      (APDS) was demonstrated by ERCP with mild dilatation of the common bile duct.
      Within one month after admininon, AFP level reached 4390 ng/ml. On operation, a
      pedunculated tumor, 6.5 x 3 cm in size, was found in the gallbladder.
      Histological examination revealed a moderately differentiated adenocarcinoma and
      positive immunohistochemical staining of cancer cells for AFP. After absolutely
      curative (stage II) resection, normal serum AFP levels were recognized. This is
      the first report of an AFP-producing cancer of the gallbladder associated with
      APDS and it was detected as a result of an attack of acute pancreatitis.

PMID- 1385252
TI  - Thyroid hormone differentially regulates rat intestinal brush border enzyme gene
      expression.
AB  - Thyroid hormone [triiodothyronine (T3)] has been shown to play a critical role in
      the growth and maturation of the mammalian small intestine, but its mechanism of
      action has not been well studied. In the current study, an animal model of
      hypothyroidism and hyperthyroidism was used to study the effects of T3 on the
      small intestine. Adult rats were treated with propylthiouracil for a 6-week
      period and then given injections of either saline (hypothyroid) or 30
      micrograms/100 g body wt of T3 (hyperthyroid). Northern blot analyses showed
      marked differential regulation of brush border enzyme gene expression. Lactase
      messenger RNA (mRNA) levels decreased approximately 75% along the length of the
      small intestine, whereas sucrase levels were unchanged. The intestinal alkaline
      phosphatase mRNA species were upregulated by T3, especially the 3-kilobase band,
      which increased most dramatically in jejunum. Further experiments showed
      significant levels of both the alpha-1 and beta-1 T3 receptor mRNAs within the
      small intestinal mucosa. Histological examination showed that T3 treatment causes
      marked villus hyperplasia throughout the length of the small intestine. These
      results provide insight into the mechanism by which T3 exerts its influence on
      the growth and differentiation of the intestinal epithelium.

PMID- 1385253
TI  - Effect of cholylsarcosine on hepatic cholesterol and bile acid synthesis and bile
      secretion in rats.
AB  - The regulatory and secretory properties of cholylsarcosine (C-sar), a synthetic
      conjugated bile acid analogue that resists deconjugation and dehydroxylation,
      were compared with those of the natural conjugates of cholic acid. After
      continuous intraduodenal infusion of cholylsarcosine (C-sar), cholyltaurine (C
      tau), or cholylglycine (C-gly) at 36 mumol/100 g.h, the infused bile acid in each
      case became the predominant biliary bile acid. After 48 hours, infusion of C-sar,
      C-tau, and C-gly suppressed the activity of cholesterol 7 alpha-hydroxylase (C7
      alpha H; rate-limiting for bile acid synthesis) by 65%, 78%, and 92%,
      respectively, compared with biliary fistula controls. After C-sar infusion,
      levels of C7 alpha H protein, messenger RNA, and transcriptional activity were
      depressed to the same extent as specific activity, indicating that C-sar, like C
      tau, down-regulates C7 alpha H principally at the level of gene transcription.
      All three bile acids also suppressed activity of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase (rate-limiting for cholesterol synthesis). Both short- and
      long-term, the three cholyl conjugates caused similar increases in bile flow and
      in biliary secretion of cholesterol and phospholipid. It is concluded that in the
      rat, cholyl conjugates per se can suppress cholesterol and bile acid biosynthesis
      without prior conversion to deoxycholate. The effects of C-sar on hepatic
      cholesterol and bile acid synthesis as well as on induced bile flow and biliary
      lipid secretion are essentially identical to those of the naturally occurring
      cholyl conjugates.

PMID- 1385255
TI  - The origin of and subcellular mechanisms causing pancreatic bicarbonate
      secretion.
AB  - In recent years, there has been a rapid growth in knowledge about the subcellular
      mechanisms involved in pancreatic ductal secretion of bicarbonate. The mechanisms
      governing anion transport across the luminal membrane of duct cells have been
      well characterized. Evidence suggests that the cystic fibrosis transmembrane
      conductance regulator is a cyclic adenosine monophosphate-regulated Cl-
      conductance in the luminal membrane that plays a pivotal role in ductal
      bicarbonate secretion by recirculating the Cl- imported into duct cells through
      Cl(-)-HCO3- exchange. The mechanisms governing ion transfer across the
      basolateral plasma membrane of duct cells are less well defined. There is some
      evidence suggesting that secretin may cause exocytotic insertion of proton pumps
      into the basolateral plasma membrane. Once inserted into the plasma membrane,
      proton pumps could engage in primary active electrogenic H+ ion transport to
      interstitial tissue while secondary active HCO3- secretion occurs over the
      luminal membrane through Cl(-)-HCO3- exchangers coupled in parallel with the
      cystic fibrosis transmembrane conductance regulator. These and other subcellular
      phenomena related to ductal secretory function are reviewed.

PMID- 1385254
TI  - Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss
      of surface antigen.
AB  - Polymerase chain reaction (PCR) was used to detect hepatitis B virus DNA in the
      sera and livers of nine patients with chronic hepatitis B after treatment-induced
      or spontaneous loss of serum hepatitis B surface antigen. Patients were evaluated
      at intervals ranging from 3 to 67 months after disappearance of hepatitis B
      surface antigen. PCR was performed using primer pairs from the surface and core
      gene regions, and surface gene products were quantitated. Liver tissue was also
      evaluated by in situ hybridization to assess viral transcription. Five of the
      nine patients had viral DNA detectable in serum by PCR. Quantitation of
      polymerase chain reaction products in serum and liver showed that the DNA levels
      tended to decline progressively after antiviral therapy. Six of seven surface
      antigen-negative patients tested had detectable viral DNA in the liver, and four
      of the six DNA-positive patients were negative for DNA in serum by PCR. None had
      surface gene messenger RNA. Thus, it is concluded that hepatitis B virus DNA may
      be detectable by PCR in liver tissue years after the disappearance of hepatitis B
      surface antigen, even in the absence of detectable hepatitis B virus DNA in
      serum.

PMID- 1385256
TI  - Complex cellular recognition events in acute inflammation.

PMID- 1385257
TI  - [Antigenic composition of serum proteins of the Inv system in normal conditions
      and in patients with hematologic diseases among the Armenian population].
AB  - Inv (1) antigen distribution was studied in 568 normal subjects and in 354
      hematological patients in the Armenian population. Inv (1) antigen was detected
      in 16.7% of the normal Armenians studied. The incidence rate of Inv (1) factor
      does not depend on the distribution of phenotypes of ABO system, rhesus factor
      (D), and the sex of the subjects investigated. Inv (1) antigen incidence rate in
      patients with acute leukemia, chronic lymphocytic leukemia, iron deficiency
      anemia, lymphogranulomatosis, idiopathic thrombocytopenic purpura, autoimmune
      hemolytic anemia was similar to that in the control, and only patients with
      chronic myeloid leukemia had significantly decreased levels of Inv (1) antigen:
      6.8% as compared to 16.7% in the population.

PMID- 1385258
TI  - GM1-ganglioside regulation of EGF-induced gastric mucosal calcium channel
      activation.
AB  - 1. Calcium channels, isolated from gastric epithelial cell membranes when
      reconstituted into phosphatidylcholine vesicles exhibited active 45Ca2+ uptake as
      evidenced by a dose dependent response to calcium channel activator, BAY K8644,
      and antagonist, PN200-110. 2. The channels on epidermal growth factor (EGF)
      binding in the presence of ATP showed an increase in tyrosine phosphorylation of
      55 and 170 kDa calcium channel proteins. Such phosphorylated channels following
      reconstitution into the vesicles displayed a 48% greater 45Ca2+ uptake than that
      of the controls. 3. The binding of EGF to calcium channel protein was inhibited
      by GM1-ganglioside reaching maximum inhibition of 65% at 40 nM GM1. In contrast,
      calcium channel antagonist, PN200-110, had no effect on EGF binding. 4. The EGF
      stimulated calcium channel protein phosphorylation was inhibited by GM1. This
      inhibitory effect was mainly reflected in the decrease of tyrosine
      phosphorylation of 55 and 170 kDa proteins. 5. The results suggest the
      participation of GM1-ganglioside in the regulation of EGF-stimulated gastric
      mucosal calcium channel activation.

PMID- 1385259
TI  - Effects of calcium channel antagonists and Bay K 8644 on the analgesic response
      to pentazocine and U 50488H.
AB  - 1. The effects of diltiazem, nifedipine and verapamil and the calcium channel
      agonist Bay K 8644 on the analgesic responses to the subcutaneous (s.c.) or
      intracerebroventricular (i.c.v.) administration of pentazocine and U 50488H were
      investigated in mice. 2. The three calcium channel antagonists and Bay K 8644
      reduced the number of writhes induced by the intraperitoneal administration of
      acetic acid. 3. The analgesic responses to the low doses of pentazocine (s.c.)
      were additive with the effects of diltiazem, nifedipine or Bay K 8644; while, in
      contrast, the higher doses produced underadditive responses. Only verapamil
      increased the effects of the i.c.v. administration of the opioid. 4. The effects
      of U 50488H (s.c.) were additive with those of diltiazem and Bay K 8644;
      verapamil only increased the response to the lower dose of the opioid. Nifedipine
      plus pentazocine always induced underadditive responses. The i.c.v. effects of U
      50488H were only increased by verapamil. 5. These findings are discussed in
      relation with a possible interaction of kappa agonists with calcium channels in
      the central nervous system.

PMID- 1385260
TI  - Hormones regulating hepatic glycogenolysis in two chelonians use cyclic AMP, and
      not Ca2+, as intracellular messenger.
AB  - In teleosts, lungfish, amphibians, and a reptile, Amphibolurus nuchalis, hormonal
      stimulation of hepatic glycogenolysis is mediated by a rise in intracellular
      cyclic AMP concentration. In mammals, by contrast, the inositol
      trisphosphate/Ca2+/diacylglycerol signal transduction pathways are also involved.
      The present study describes the hormonal regulation of hepatic glycogenolysis in
      adult long-necked turtles, Chelodina longicollis, and hatchlings of the
      loggerhead turtle, Caretta caretta. Adrenaline and glucagon, but not
      neurohypophysial peptides, stimulated glycogenolysis, glycogen phosphorylase
      activity, and accumulation of cAMP in cultured liver pieces from either C.
      longicollis or C. caretta. The actions of adrenaline were blocked by a beta
      adrenergic antagonist, propranolol, but were unaffected by an alpha-adrenergic
      antagonist, phentolamine. The effects of adrenaline were maintained in Ca(2+)
      free medium containing EGTA, and were not mimicked by the Ca2+ ionophore, A23187.
      The beta-adrenergic ligand, [125I]iodocyanopindolol (ICP), specifically bound to
      membranes prepared from C. longicollis liver, with a calculated KD of 59 pM and a
      Bmax of 171 fmol/mg protein. The adrenergic ligands, propranolol, isoprenaline,
      adrenaline, phenylephrine, phenoxybenzamine, noradrenaline, and phentolamine
      displaced ICP with KD's of 50 nM, 5 microM, 22 microM, 140 microM, 180 microM,
      250 microM, and 1 mM, respectively. The alpha-adrenergic ligands, prazosin and
      yohimbine, did not bind specifically to the membranes, although prazosin did bind
      to membranes prepared similarly from rat liver. Thus the glycogenolytic actions
      of adrenaline are mediated via beta-adrenergic receptors in liver from C.
      longicollis and C. caretta and alpha-adrenergic receptors may play no role in the
      control of hepatic metabolism in these chelonians.

PMID- 1385261
TI  - Effects of estradiol valerate on the uterus of the musk shrew (Suncus murinus
      L.).
AB  - The effects of exogenous estradiol valerate on some uterine characteristics of
      the musk shrew were investigated. Treatment with the steroid for either 1 day or
      7 days did not noticeably alter luminal epithelial cell height, endometrial gland
      epithelial cell height or diameter, or number of endometrial glands. The
      reciprocal values of cell density of circular muscle and deep endometrial layers
      and endometrium-to-myometrium ratio of the uterus increased significantly in
      response to 7 days of steroid administration. After 1 day of steroid treatment
      the numbers of mast cells in different layers of the uterus (i.e., meso-, myo-,
      and endometrium) were unchanged, but after 7 days there were significant
      increases in the number of mast cells in meso- and myometria. The number of
      eosinophils in all three layers of the uterus increased significantly in response
      to the treatment of estradiol for 1 day or for 7 days. The increase was greater
      in the 7-day group. Neither uterine DNA nor RNA contents changed following
      administration of the steroid for either group, although protein content was
      elevated significantly in the 7-day group. Estradiol administration thus evokes
      small but subtle changes in the uterus of the musk shrew.

PMID- 1385262
TI  - Semi-automatic analysis of unit channel conductance from voltage ramp records.
AB  - An IBM PC-compatible computer program, RAMP, for evaluation of single-channel
      recordings acquired using voltage ramp protocols is presented. The program uses
      semi-automatic procedures to make necessary corrections to a record (e.g.
      subtraction of baseline shift) and to measure all channel slope conductances as
      well as reversal potentials. The output is either a hardcopy of graphic display,
      which includes the calculated parameters, or data in ASCII format for further use
      (e.g. plots using various graphic software). Originally, the software was
      developed for the evaluation of voltage ramp records of single channel data from
      maxi chloride channels in myoblasts of a muscle cell line (Hurnak and Zachar
      1992). Records from these membrane patches were also used in this work to
      demonstrate basic principles of the software and its practical use in evaluating
      single channel records obtained in response to the application of voltage ramps.
      The channel conductances calculated from ramp records were compared with those
      obtained by classical evaluation procedures from voltage step records.

PMID- 1385263
TI  - RNA sequence analysis shows that the symbionts in the ciliate Metopus contortus
      are polymorphs of a single methanogen species.
AB  - The polymerase chain reaction was used to amplify and partially sequence the 16S
      ribosomal RNA genes of symbiotic bacteria within the anaerobic ciliate Metopus
      contortus. In situ probing with fluorescent oligonucleotides showed that the
      amplified sequences originated from a single species of archaebacterium which is
      closely related to Methanocorpusculum parvum. The probed symbionts exhibited a
      variety of shapes and sizes. These data support the hypothesis, first proposed on
      the basis of electron microscopy, that the symbionts undergo a morphological
      transformation as part of the symbiotic process.

PMID- 1385264
TI  - Phylogenetic and chemotaxonomic characterization of Acidaminococcus fermentans.
AB  - The phylogenetic position of Acidaminococcus fermentans was determined by
      comparative sequence analysis of the 16S rRNA. This Gram-negative bacterium is a
      member of the Sporomusa cluster that is defined by other Gram-negative bacteria,
      i.e. Sporomusa, Megasphaera, Selenomonas, Butyrivibrio, Pectinatus, and
      Zymophilus. The branching point of this group within the radiation of Gram
      positive bacteria of the Clostridium/Bacillus subphylum and adjacent to
      Peptococcus niger could be confirmed. Chemotaxonomic data were provided for a
      more detailed characterization of A. fermentans.

PMID- 1385265
TI  - Cell wall-less, free-living spirochetes in Antarctica.
AB  - The phylogeny of an Antarctic, cell wall-less, bacterial strain was determined by
      sequencing PCR amplified 16S rDNA, and comparison of the sequence with other
      bacterial 16S rRNA sequences available in databanks. Although the strain was
      phenotypically very similar to members of the genus Anaeroplasma, phylogenetic
      analyses showed it was a member of the order Spirochaetales. Until now, the order
      was one of the few bacterial orders in which phylogeny was reflected in a uniform
      morphology of its members. The viability of wall-less cells in cultures of
      spirochetes and spirochetal infective material warrants reinvestigation.

PMID- 1385266
TI  - A cladistic analysis of phenotypic associations with haplotypes inferred from
      restriction endonuclease mapping and DNA sequence data. III. Cladogram
      estimation.
AB  - We previously developed a cladistic approach to identify subsets of haplotypes
      defined by restriction endonuclease mapping or DNA sequencing that are associated
      with significant phenotypic deviations. Our approach was limited to segments of
      DNA in which little recombination occurs. In such cases, a cladogram can be
      constructed from the restriction site or sequence data that represents the
      evolutionary steps that interrelate the observed haplotypes. The cladogram is
      used to define a nested statistical design to identify mutational steps
      associated with significant phenotypic deviations. The central assumption behind
      this strategy is that any undetected mutation causing a phenotypic effect is
      embedded within the same evolutionary history that is represented by the
      cladogram. The power of this approach depends upon the confidence one has in the
      particular cladogram used to draw inferences. In this paper, we present a
      strategy for estimating the set of cladograms that are consistent with a
      particular sample of either restriction site or nucleotide sequence data and that
      includes the possibility of recombination. We first evaluate the limits of
      parsimony in constructing cladograms. Once these limits have been determined, we
      construct the set of parsimonious and nonparsimonious cladograms that is
      consistent with these limits. Our estimation procedure also identifies haplotypes
      that are candidates for being products of recombination. If recombination is
      extensive, our algorithm subdivides the DNA region into two or more subsections,
      each having little or no internal recombination. We apply this estimation
      procedure to three data sets to illustrate varying degrees of cladogram ambiguity
      and recombination.

PMID- 1385267
TI  - Mutagenic analysis of the promoter of the Streptomyces fradiae beta-lactamase
      encoding gene.
AB  - The Streptomyces fradiae beta-lactamase promoter (PblaF) was sequenced and
      characterized by promoter probing, primer extension, and exonuclease III-mediated
      deletions. The transcription start point (tsp) was the same in both S. lividans
      and S. fradiae. Oligodeoxyribonucleotide-directed random mutations and site
      specific mutations were introduced in the promoter region. The effects of these
      mutations on transcription were assayed by an RNA colony hybridization method.
      This analysis identified cis-acting sequence determinants located similarly to
      the -10 and -35 regions of a typical Escherichia coli promoter. Also, a change in
      the distance between these regions from 19 to 17 bp drastically reduced promoter
      activity. PblaF was shown not to be recognized by sigma-whiG or by sigma-hrdA,
      hrdC, or hrdD. Sequence alignment of PblaF to sigma factor-classified
      Streptomyces promoters revealed little homology. Thus, PblaF is probably
      recognized by an as yet unidentified sigma factor.

PMID- 1385268
TI  - Protease inhibitor display M13 phage: selection of high-affinity neutrophil
      elastase inhibitors.
AB  - We report display of the complete protease inhibitor (Kunitz) domain, BPTI, on
      the surface of bacteriophage M13 as a fusion to the gene III product. Phage that
      display BPTI bind specifically to anti-BPTI antibodies, trypsin and
      anhydrotrypsin. A point mutation of BPTI [Lys15-->Leu(K15L)] alters the binding
      specificity of fusion phage such that a human neutrophil elastase-binding
      phenotype is conferred while a trypsin-binding phenotype is eliminated. Phage
      were eluted from an immobilized protease with step gradients of decreasing pH.
      Phage that display Kunitz domains having higher affinity for the immobilized
      protease exhibit characteristic pH elution phenotypes, indicating that bound
      display phage can be selectively recovered from an affinity matrix. Utilization
      of this technology should enable the selection of remodeled protease inhibitors
      exhibiting novel binding specificities.

PMID- 1385269
TI  - [Effects of hexachlorane on enzyme spectrum of the liver, alveolar macrophages
      and blood serum in experimental animals].

PMID- 1385270
TI  - [Experimental research on the efficacy of terrilytin in silicosis].
AB  - Experimental silicosis was induced by quartz-containing dust administered
      intratracheally to Wistar male rats. Proteoclastic enzymes terrilytine was found
      to arrest pulmonary fibrosis, which was proved by inhibited development of
      silicotic granulomas and their lowered fibrosis. Terrilytine was most effective
      when inhaled in a dose of 0.08 PU per rat. Injected intraperitoneally,
      terrilytine in the dose elevated from 0.1-0.2 to 0.3 PU inhibited fibrosis
      developing in the presence of marked serous desquamative alveolitis.
      Incorporation of the enzyme in the cholesterol-lecithin liposomes prevents this
      side effect in the lungs. Liposomes injected intraperitoneally do not influence
      the development of pulmonary fibrosis in silicosis.

PMID- 1385271
TI  - [The evaluation of alternative fuels for automobile transport and the resolution
      of hygienic and ecological tasks].
AB  - Automobile transport ranks first among the pollutants of big cities by nitrogen
      and carbogen oxides nowadays. Other kinds of fuel are to reduce the level of
      pollution. Evaluation of the liquid and gaseous fuel showed their positive
      hygienic and ecological prospects.

PMID- 1385273
TI  - Acute pancreatitis complicating Crohn's disease: mere coincidence or causality?
AB  - An example of acute pancreatitis developing five weeks after initial treatment
      with 5-aminosalicylic acid (5-ASA) and methylprednisolone for severe Crohn's
      disease is reported in a 37 year old female patient. She had undergone
      cholecystectomy for gall stones some years earlier. There was no evidence of
      acute or chronic pancreatitis. No morphological changes of the upper
      gastrointestinal tract were found except for some irregularity of the main
      pancreatic duct and the secondary ducts on endoscopic retrograde pancreatography.
      Rechallenge with 5-ASA did not induce recurrent pancreatitis or changes in
      pancreatic enzymes. This case report supports the concept of an association
      between acute pancreatitis and Crohn's disease.

PMID- 1385272
TI  - Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.
AB  - The importance of platelet activating factor in acute pancreatitis was examined
      by determining the tissue content of endogenous platelet activating factor and
      the protective effects of TCV-309, a highly selective platelet activating factor
      blocker, against caerulein induced pancreatitis in rats. Infusion of caerulein
      (10 micrograms/kg/h) for five hours resulted in about 70% increase in pancreatic
      weight, 22% rise in protein content, 50% reduction in tissue blood flow, nine
      fold increase in tissue level of platelet activating factor and 165% rise in
      plasma amylase as well as histological evidence of acute pancreatitis. Such
      infusion of caerulein in chronic pancreatic fistula rats caused a marked increase
      in protein output from basal secretion of 10 mg/30 minutes to 40 mg/30 minutes in
      the first hour of infusion followed by a decline in protein output to 15-20 mg/30
      minutes in the following hours of the experiment. Exogenous platelet activating
      factor (50 micrograms/kg) injected ip produced similar alterations in weight,
      protein content, blood flow, and histology of the pancreas but the increment in
      serum amylase was significantly smaller and pancreatic secretion was reduced
      below the basal level. TCV-309 (50 micrograms/kg) given ip before caerulein or
      platelet activating factor administration significantly reduced the biochemical
      and morphological alterations caused by caerulein and abolished those induced by
      exogenous platelet activating factor. These results indicate that platelet
      activating factor plays an important role in the pathogenesis of acute
      pancreatitis probably by reducing the blood flow and increasing vascular
      permeability in the pancreas.

PMID- 1385275
TI  - Efficacy of granulocyte colony-stimulating factor (G-CSF) on neutropenia in
      zidovudine-treated patients with AIDS and ARC: a preliminary report.

PMID- 1385274
TI  - The CD34 hemopoietic progenitor cell associated antigen: biology and clinical
      applications.
AB  - CD34, which was first detected in hemopoietic and lymphopoietic progenitors, is a
      heavily glycosylated Type I transmembrane protein that does not share any
      significant similarity with other transmembrane proteins. Its functions are still
      unknown. Several monoclonal antibodies were raised against CD34, and at least 4
      different epitopes could be recognized. CD34 expression is confined to a few cell
      lines, to 1-4% of adult bone marrow mononuclear cells (including marrow
      repopulating cells, all multipotent and committed myeloid progenitors, B and T
      lymphoid precursors, osteoclast precursors, and most likely the precursors for
      stromal cells), and to less than 1% of peripheral blood mononuclear cells. In non
      lymphohemopoietic tissues its expression is confined to endothelial cells and to
      some cells of the skin. In malignancies, CD34 expression is not fully elucidated.
      Immature hemolymphopoietic malignancies (namely acute leukemias) and the blast
      cells of chronic myeloid leukemia are frequently positive. Chronic
      lymphoproliferative disorders and lymphomas are negative. Among other tumors,
      only vascular derived tumors are positive. Clinical applications of CD34+ cells
      include autologous transplantation of putative CD34+ stem cells isolated by
      positive selection from the bone marrow, and transplantation of autologous
      peripheral blood stem cells, using the proportion and number of CD34+ cells as a
      guideline for the harvesting procedure.

PMID- 1385276
TI  - CD34-positive cell selection by immunomagnetic beads and chymopapain.
AB  - BACKGROUND: Pluripotent hemopoietic stem cells, progenitors of all
      hemolymphopoietic lineages, and clonogenic cells from many patients with acute
      nonlymphocytic leukemia (ANLL) and chronic myeloid leukemia (CML) express the
      CD34 antigen on their surface. Isolation of these cell populations is of primary
      experimental and clinical importance. METHODS: Six bone marrow (BM) and 10
      peripheral blood (PB) samples were obtained from 2 normal individuals, 3 patients
      with CML and 9 with ANLL. The CD34+ cell fraction was isolated using MY10
      antibody, sheep anti-mouse immunomagnetic beads and the enzyme chymopapain.
      Indirect immunofluorescence and semisolid culture were employed to evaluate the
      percentage of CD34+ cells and that of clonogenic cells in each cell fraction.
      RESULTS: The frequency of CD34+ cells in the original unseparated populations was
      (mean +/- SE) 24.3 +/- 7.3%, and reached 85.0 +/- 2.7% in the isolated CD34
      positive fractions; in the negative fractions it was only 2.7 +/- 1.7%. According
      to these results, the great majority of clonogenic cells was separated in the
      CD34-positive fractions and depleted in those CD34-negative. Moreover,
      chymopapain was shown to be non-toxic to the clonogenic cells. CONCLUSIONS:
      Positive immunoselection using My10 Ab, immunomagnetic beads and chymopapain is a
      method for isolating almost pure progenitors from the BM and PB of normal
      individuals and patients with myeloid leukemias.

PMID- 1385277
TI  - CEOP/PEB alternating chemotherapy in advanced intermediate and high-grade non
      Hodgkin's lymphomas.
AB  - BACKGROUND AND METHOD: From February, 1987 to July, 1990, 28 patients (M/F =
      16/12; median age = 60.5 yrs) affected by intermediate (22) or high-grade (6)
      advanced stage (III = 8; IV = 20) NHL were given a median (range 4-10) of 8
      cycles of CEOP (Cyclophosphamide, Epirubicin, Vincristine and Prednisone),
      alternated every 21 days with PEB (Cisplatin, Etoposide, Bleomycin). RESULTS:
      Nineteen (68%) pts. achieved a CR, 5 (18%) a PR, and 4 (14%) experienced
      progressive disease (PD); 11/19 CRs subsequently relapsed within a median (range
      3-15) time of 8 mos.. After a follow-up ranging from 6 to 42+ (median 18) mos.,
      the 3-year actuarial overall survival (OS) was 51% and shifted to 18% at 42 mos.
      After 7-42+ (median 19) mos., 14/19 (73%) Crs were still alive with 63% of them
      predicted to survive at 3 years. The projected 3-year disease-free survival (DFS)
      for these pts. after 1-36+ (median 8) mos. was 28%. DISCUSSION: CEOP/PEB
      alternating chemotherapy failed to improve the therapeutic results we obtained in
      a previous study with CEOP alone. Toxicity was moderate, but higher than
      expected.

PMID- 1385278
TI  - A case of spinal cord compression by extramedullary haemopoiesis in a
      thalassaemic patient: a putative role for hydroxyurea?
AB  - We report a case of homozygous beta thalassaemia who developed chronic
      paraparesis due to spinal cord compression by paravertebral extramedullary
      masses. Our patient was successfully treated with hypertransfusion and
      hydroxyurea. This drug in addition to its well-known cytostatic effects, may be a
      good alternative in conditions analogous to our case. This action of hydroxyurea
      can also be attributed to its favourable effect on foetal haemoglobin production.

PMID- 1385279
TI  - Effect of FK-506 and cyclosporin A on in vitro CFU-GM growth in severe aplastic
      anemia patients.

PMID- 1385280
TI  - [Experimental study using porous, vascularizable polytetrafluoroethylene in
      preformed free flaps].
AB  - Following radical tumor resections or severe trauma, particularly in the head and
      neck region, cartilage or bone grafts serve as frame work in defect
      reconstruction. As an alternative, porous plastic material was used for preformed
      free flaps in an experimental study with 28 New Zealand rabbits. Due to ingrowth
      of fibrous tissue and capillaries, it was possible to obtain prefabricated flaps
      consisting of vascularized porous plastic, a thin layer of fatty gliding tissue
      and full thickness skin graft. The blood supply of all three layers of the
      transplant was confirmed by microangiography, Tc 99 m labeled red blood cells and
      histological examination.

PMID- 1385281
TI  - [Effect of Z-103 on wound healing by dermal incision in guinea pigs].
AB  - We investigated the effects of Z-103, ZnSO4, L-carnosine and solcoseryl on wound
      healing by dermal incision in guinea pigs. The tensile strength, hydroxyproline
      contents and the value of angiogenesis (carmine contents) at the wounded site of
      dorsal skin were used as indices of wound healing. Z-103, given daily s.c.,
      increased the tensile strength and hydroxyproline contents on day 4 after
      operation in a dose-dependent manner; in particular, the effect of 10 mg/kg of Z
      103 was nearly equal to that of solcoseryl at 0.5 ml/animal. Moreover, Z-103 10
      mg/kg increased the value of angiogenesis on day 3 after the operation. On the
      other hand, ZnSO4 and L-carnosine, components of Z-103, also similarly increased
      the tensile strength and hydroxyproline contents. These results suggest that Z
      103 possessed an accelerative action on wound healing, and these effects may be
      due to the activity of its components, ZnSO4 and L-carnosine.

PMID- 1385282
TI  - Effect of pesticides on oestradiol-receptor complex formation in rat uterus
      cytosol.
AB  - The effect of gamma-1,2,3,4,5,6-hexachlorocyclohexane (lindane), 2-chloro-4
      ethylamino-6-isopropylamino-s-triazine (atrazine) and 2-methylthio-4,6-bis
      isopropylamino-s-triazine (prometryne) on the formation of a specific oestradiol
      receptor complex in the rat uterus cytosol has been examined in vitro and in
      vivo. Both in vitro and in vivo, the pesticides significantly (P < 0.001)
      inhibited the formation of the complex in the rat uterus cytosol. The decrease in
      the number of free specific binding sites on the receptors was determined. The
      affinity of binding was not modified under the influence of pesticides, and the
      Kd value was of the same order of magnitude (10(-9) M). The inhibition was found
      to be fully non-competitive.

PMID- 1385284
TI  - [The CUP syndrome--malignant disease with unknown primary tumor. Part 2:
      Histology--immunohistology].

PMID- 1385283
TI  - Genotoxicity studies in vitro and in vivo on carminic acid (natural red 4).
AB  - The potential genotoxic activity of carminic acid (CAS no. 1260-17-9; EINECS no.
      215-023-3; C.I. no. 75410), a component of natural red colouring products
      (cochineal: CAS no. 1343-78-8; EINECS no. 215-680-6; C.I. no. 75470), used in
      food, cosmetics and drugs, has been evaluated by means of a series of short-term
      tests in vitro and in vivo, namely Salmonella reverse mutation, chromosome
      aberrations and sister chromatid exchanges in vitro on Chinese hamster ovary
      cells, and the mouse micronucleus test. All studies have produced negative
      results. The data obtained strongly support the non-mutagenic/non-carcinogenic
      activity of this compound. Genotoxicity data previously obtained for carminic
      acid, concerning the induction of a series of other genetic endpoints in
      different test systems, have also been considered, as have recent findings that
      indicate lack of carcinogenic activity in the cochineal preparation containing
      29.8% carminic acid.

PMID- 1385285
TI  - Effects of riluzole (2-amino-6-trifluoromethoxy benzothiazole) on striatal
      neurochemical markers in the rat, with special reference to the dopamine,
      choline, GABA and glutamate synaptosomal high affinity uptake systems.
AB  - Riluzole, a new compound with anticonvulsant properties, was found to induce a
      dose-dependent decrease in the uptake of 3H-dopamine, 3H-GABA and 3H-glutamate
      into striatal synaptosomes when added to the incubation medium or after in vivo
      administration, whereas an inhibition of 3H-choline uptake was detected only in
      the in vitro experiments. Interestingly, riluzole affected 3H-dopamine and 3H
      glutamate uptake differentially since 3H-dopamine uptake was found to be more
      sensitive to the compound. Moreover, riluzole inhibited 3H-dopamine uptake
      competitively and 3H-glutamate uptake non-competitively, which further suggests
      that the action of the compound is selective. After in vivo injection, riluzole
      did not affect the striatal dopamine, DOPAC, serotonin, 5HIAA, glutamate,
      aspartate or GABA contents. Since this compound was previously reported to induce
      a decrease in the spontaneous release of glutamate, serotonin, dopamine and
      possibly acetylcholine, the hypothesis is put forward that riluzole may, at least
      at high concentrations, have general effects on the striatal nerve terminals
      affecting both the uptake and release processes. This action may be correlated
      with the recently identified blocking properties of the compound on the sodium
      channels, as previously shown for local anaesthetics.

PMID- 1385286
TI  - Prevalence of antibodies to hepatitis C virus among Saudi patients with chronic
      liver diseases.
AB  - The prevalence of antibodies against hepatitis C virus (anti-HCV) was determined
      in 55 patients with chronic liver diseases including liver cirrhosis (42
      patients), liver cirrhosis and hepatocellular carcinoma (8 patients), and chronic
      active hepatitis (4 patients). A total of 63.6% of these patients were positive
      for anti-HCV, a significantly higher prevalence than the rate of 3.9% observed in
      488 asymptomatic volunteers. Of the 42 patients with liver cirrhosis 16 (38.1%)
      had positive anti-HCV without any markers of hepatitis B virus (HBV), while 12
      (28.6%) had markers of neither HCV nor HBV infection. Our findings suggest that
      HCV infection may play a significant role in the pathogenesis of chronic liver
      disease in Saudi Arabia, which is an area of endemic HBV infection. Screening for
      anti HCV should be considered mandatory in patients with chronic liver disease
      (CLD) especially where the etiology appears obscure.

PMID- 1385287
TI  - Intrahepatic lymphocyte subpopulations and HLA class I antigen expression by
      hepatocytes in chronic hepatitis C.
AB  - The lymphocyte subpopulations in the peripheral blood and liver were studied in
      17 patients with chronic active hepatitis type C (CAH C) by immunoenzymatic and
      immunofluorescence techniques, using mono-specific T cell antibodies and other
      reagents. The peripheral blood subsets showed no significant differences between
      the patients with CAH C and normal controls. In the liver, CD8-positive cells
      were predominant over CD4- and Leu 7-positive cells. Leu 7-, CD4-, and CD11
      positive lymphocytes were all few in number. HLA class I antigen was expressed
      diffusely on the cell surfaces of the hepatocytes. Serum levels of soluble
      interleukin 2 receptor (sIL2R) in the CAH C patients were significantly higher
      than in normal controls (p less than 0.01). In CAH C, sIL2R levels were higher
      during exacerbations than during remissions (p less than 0.01). These results
      suggest that cytotoxic T cells (CD8- positive, CD4-negative, and CD11-negative)
      may play an important role in the pathogenesis of hepatocyte injury in patients
      with CAH C.

PMID- 1385288
TI  - [Experimental allergic encephalomyelitis: immunopathological analysis of
      antigenic reactivity and loss of encephalitogenicity].
AB  - Experimental allergic encephalomyelitis (EAE) is an autoimmune demyelinating
      disease of the central nervous system (CNS). EAE can be induced by immunization
      with myelin basic protein (MBP) or passive transfer of MBP-reactive T cell lines
      and clones. We established several T-cell clones from SJL/J mice by immunization
      with whole rat MBP or a synthetic peptide encompassing guinea pig MBP 89-101
      which contains the encephalitogenic determinant for SJL/J mice. One clone was
      found to have lost its encephalitogenicity during long-term passages in vitro,
      although this clone maintains its specific reactivity to the encephalitogenic
      determinant. To clarify the difference between the encephalitogenic T cell clone
      (4b. 14a) and the non-encephalitogenic T-cell clone (4b. 14a/n), we examined the
      suppressive activity of 4b. 14a/n on the reactivity to antigen of 4b. 14a,
      various lymphokine production and adhesion molecules expression of 4b. 14a and
      4b. 14a/n. The culture fluid of the both 4b. 14a/n and 4b. 14a revealed a
      suppressive effect on the proliferation of 4b. 14a stimulated by MBP 89-101, and
      the effect was not different between these clones. In lymphokine production, the
      activities of lymphotoxin, interferon or interleukin-2 were not different between
      encephalitogenic clones (4b.14a and TNT-1) and 4b. 14a/n, whereas the activity of
      tumor necrosis factor-alpha, passively secreted by antigen presenting cell, was
      higher in culture media of 4b. 14a/n. Examination of adhesion molecule expression
      of 4b.14a/n failed to show any differences in expression of lymphocyte function
      associated antigen-1 (LFA-1) alpha and CD2 in the comparison with 4b. 14a.
      However, LFA-1 beta expression of 4b. 14a/n was always less than of 4b. 14a. The
      present studies indicated that the lack of encephalitogenicity of T-cell clones
      which were responsive to an encephalitogenic determinant depends not on the
      difference in major lymphokines production but partially on adhesion molecules
      expression which was decreased in non-encephalitogenic T-cell clone.

PMID- 1385289
TI  - Synergistic effects of murine stem cell factor in combination with a variety of
      cytokines on the expansion of murine hematopoietic progenitor cells in short-term
      suspension cultures.
AB  - In the present study, it is represented that the ability of murine stem cell
      factor (SCF) to expand hematopoietic progenitor cells in short-term suspension
      culture when used alone or with IL-1 beta, IL-3, IL-6, M-CSF and IL1 beta Plus IL
      3. SCF alone had a limited effect on the expansion of early primitive
      hematopoietic progenitor cells (CFU-HPP: high proliferative potential colony
      forming unit, and CFU-S: colony forming unit in spleen) even at a high
      concentration, but expanded mature hematopoietic progenitor cells (CFU-GM: colony
      forming unit-granulocyte/macrophage, and BFU-E: burst forming unit-erythroid)
      markedly at low concentrations. When SCF was used in combination with other
      cytokines, the expansion of primitive hematopoietic progenitor cells was
      significantly increased; namely, CFU-HPP were expanded approximately 2 to 5-fold
      compared with SCF alone. A marked expansion of hematopoietic progenitor cells was
      observed in a combination of SCF plus IL-1 beta plus IL-3. In this setting, CFU-S
      was increased 2.2-fold compared with the number of CFU-S in fresh bone marrow and
      CFU-HPP were increased 8.5-fold compared with the number of primary CFU-HPP.
      These results suggest that these factors may be utilized in experiments of murine
      bone marrow transplantation (BMT) and also in human BMT. Namely, the adequate
      number of hematopoiesic progenitor cells and stem cells required for the
      successful engraftment can be obtained from small volume of peripheral or bone
      marrow blood by this procedure, thus obtiating the donor's burden.

PMID- 1385290
TI  - Aflatoxin B1 DNA adducts in smeared tumor tissue from patients with
      hepatocellular carcinoma.
AB  - Aflatoxins are well-known animal hepatocarcinogens, but the association between
      aflatoxins and human hepatocellular carcinoma remains to be elucidated. A study
      method consisting of indirect immunofluorescence assay combined with densitometry
      was developed to quantitate aflatoxin B1 DNA adducts in smeared liver tissue
      obtained at the time of biopsy for diagnosis in 50 hepatocellular carcinoma
      patients in Taiwan. Monoclonal antibody 6A10, generated against the persistent
      form of the major N7 guanine adduct of aflatoxin B1, was used for detection of
      adduct. Thirty-five (70%) of the hepatocellular carcinoma samples had detectable
      levels of aflatoxin B1 DNA adducts (> or = 1/10(6) nucleotides). The detection
      rate was slightly lower in men (69%) than in women (75%), and younger patients
      had a significantly higher rate of adducts (83%) than did older ones (58%).
      Carriers of both HBsAg and HBeAg, carriers of HBsAg only and noncarriers had
      different rates of detection: 29%, 74% and 82%, respectively. Patients with
      family histories of hepatocellular carcinoma had a higher detection rate (100%)
      than did those patients without such histories (67%). No association was found
      between aflatoxin B1 DNA adducts in liver tissue and Child's score for severity
      of liver disease. The results suggest that aflatoxin B1 may be involved in the
      pathogenesis of hepatocellular carcinoma in Taiwan. Our immunohistochemical
      method for analysis of adducts in small numbers of cells from the target organ
      should improve results of monitoring for the biologically effective dose of
      aflatoxin.

PMID- 1385291
TI  - Appearance of hepatocytelike cells in the interlobular bile ducts of human liver
      in various liver disease states.
AB  - Among 1,098 liver biopsy specimens obtained from patients with various liver
      diseases characterized by liver injury, 58 epithelial cells whose cytoplasms
      stained positively by the periodic acid-Schiff stain (digested with diastase)
      were recognized in the interlobular bile ducts of 37 specimens from 36 patients.
      Light microscopic study revealed that the cytoplasms of these cells were clear or
      stained weakly eosinophilic on hematoxylin and eosin staining and that the cell
      limits were distinct. From their reaction with periodic acid-Schiff stain and
      from electron microscopic observation it was clear that these cells contained an
      abundance of glycogen and were located among the normal bile duct cells
      surrounded by basement membrane. On electron microscopy, these cells had
      microvilli of equal sizes on their luminal surfaces and many irregularly sized
      microvilluslike cell membrane projections on their basal surfaces. They rested on
      basement membrane with basal spaces. These cells varied in size from 25.0 to
      452.2 microns 2 (mean = 212.2 microns 2). In contrast, the sizes of normal bile
      duct cells and hepatocytes ranged from 20.0 to 69.3 microns 2 (mean = 34.2
      microns 2) and from 113.0 to 860.3 microns 2 (mean = 447.0 microns 2),
      respectively. Immunohistochemical study with antiserum to cytokeratin 19, albumin
      and alpha 1-antitrypsin on serially cut frozen sections showed that some of these
      cells expressed markers of bile duct cells and hepatocytes. Some cells expressed
      only the markers of hepatocytes. Computer graphic three-dimensional
      reconstruction clearly demonstrated that these cells were located sparsely (but
      sometimes in groups) among normal interlobular bile duct cells, without any
      connection to the surrounding parenchymal hepatocytes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1385292
TI  - Mapping of a gene for epidermolytic palmoplantar keratoderma to the region of the
      acidic keratin gene cluster at 17q12-q21.
AB  - Epidermolytic palmoplantar keratoderma (EPPK) (Vorner-Unna-Thost) is an autosomal
      dominantly inherited skin disease of unknown etiology characterized by diffuse
      severe hyperkeratosis of the palms and soles and, histologically, by cellular
      degeneration. We have mapped a gene for EPPK to chromosome 17q11-q23, with
      linkage analysis using microsatellite DNA-polymorphisms, in a single large family
      of 7 generations. A maximum lod score of z = 6.66 was obtained with the probe
      D17S579 at a recombination fraction of theta = 0.00. This locus maps to the same
      region as the type I (acidic) keratin gene cluster. Keratins, members of the
      intermediate filament family, the major proteins of the cytoskeleton in
      epidermis, are differentially expressed in a tissue-specific manner. One acidic
      keratin, keratin 9 (KRT9), is expressed only in the terminally differentiated
      epidermis of palms and soles. The KRT9 gene has not yet been cloned; however,
      since the genes for most acidic keratins are clustered, it is highly probable
      that it too will map to this region. We therefore propose KRT9 as the candidate
      gene for EPPK.

PMID- 1385293
TI  - Significantly higher frequency of the MspI 2.2 kb allele of the Duchenne muscular
      dystrophy intragenic probe P-20 in the Chinese population.
AB  - The P-20 intragenic marker was used to test for restriction fragment length
      polymorphisms in unrelated Chinese patients with Duchenne or Becker muscular
      dystrophy or X-linked mental retardation. In addition to polymorphism at the
      6.0/3.5 kb MspI allelic site, we found an independent and high frequency of
      polymorphism at the 2.2/1.8 kb site. This differs from results found with other
      populations.

PMID- 1385294
TI  - Chromosome aberrations in 450 sperm complements from eight controls and lack of
      increase after chemotherapy in two patients.
AB  - Four hundred fifty sperm complements from eight controls were analyzed. A
      conservative estimate of aneuploidy was 1.8% with a hyperhaploid rate of 0.9%
      (4/450). The overall frequency of structural aberrations was 8.9% (40/450). The
      proportion of X-bearing (47.5%) and Y-bearing (52.5%) sperm did not differ
      significantly. Sperm complements were analyzed from a cancer patient 9 months
      after polychemotherapy (n = 63) and from a patient being treated with Imurek
      (azathioprine) (n = 30). There was no significant increase in the incidence of
      numerical and structural chromosome aberrations in the sperm of either patient.
      The percentages of X-bearing and Y-bearing sperm were not significantly different
      from the expected 50%.

PMID- 1385295
TI  - Acyclovir vs isoprinosine (immunovir) for suppression of recurrent genital herpes
      simplex infection.
AB  - OBJECTIVE: To compare the efficacy and safety of oral acyclovir (400 mg twice
      daily) with oral isoprinosine (500 mg twice daily) in the suppression of
      recurrent genital herpes. DESIGN: Double-blind, double-dummy, randomised,
      controlled, parallel group trial. SETTING: 13 centres in UK, Belgium and Germany.
      SUBJECTS: 127 immunocompetent patients with frequently recurring genital herpes.
      MAIN OUTCOME MEASURES: Proportions of patients reporting recurrences, recurrence
      frequency, and mean duration of lesions during breakthrough recurrences in each
      treatment group during a 6 month treatment period; time to first recurrence
      during treatment and follow-up after treatment cessation. RESULTS: During
      treatment, acyclovir recipients showed significant differences (p < 0.05) when
      compared with isoprinosine recipients in terms of a lower proportion reporting
      recurrences (31% vs 96%), a reduced mean number of reported recurrences per
      patient (0.6 vs 3.6), a shorter mean duration of breakthrough lesions (6.4 days
      vs 8.2 days), and a longer mean time (standard error) to first recurrence (143.7
      (9.1) days vs 40.5 (5.4) days. The mean time to first recurrence after treatment
      cessation did not differ between the two groups. As compared with placebo
      recipients, isoprinosine treated patients had an increased recurrence frequency
      (3.6 vs 2.5) during treatment, and a shorter time to first recurrence after
      treatment cessation. All treatments were well tolerated without serious adverse
      events or toxicity. CONCLUSIONS: Acyclovir is very effective in suppressing
      recurrent genital herpes and is clearly superior to isoprinosine which is not
      clinically useful in the dosage studied.

PMID- 1385296
TI  - Laboratory investigation of Pneumocystis carinii pneumonia.

PMID- 1385297
TI  - Genetic and physical map of the interferon region on chromosome 9p.
AB  - A region of chromosome 9, surrounding the interferon-beta (IFNB1) locus and the
      interferon-alpha (IFNA) gene cluster on 9p13-p22, has been shown to be frequently
      deleted or rearranged in a number of human cancers, including leukemia, glioma,
      non-small-cell lung carcinoma, and melanoma. To assist in better defining the
      precise region(s) of 9p implicated in each of these malignancies, a combined
      genetic and physical map of this region was generated using the available 9p
      markers IFNB1, IFNA, D9S3, and D9S19, along with a newly described locus, D9S126.
      The relative order and distances between these loci were determined by multipoint
      linkage analysis of CEPH (Centre d'Etude du Polymorphisme Humain) pedigree DNAs,
      pulsed-field gel electrophoresis, and fluorescence in situ hybridization. All
      three mapping approaches gave concordant results and, in the case of multipoint
      linkage analysis, the following gene order was supported for these and other
      closely linked chromosome 9 markers present in the CEPH database: pter-D9S33
      IFNB1/IFNA-D9S126-D9S3-D9S19 -D9S9/D9S15-ASSP3-qter. This map serves to extend
      preexisting chromosome 9 maps (which focus primarily on 9q) and also reassigns
      D9S3 and D9S19 to more proximal locations on 9p.

PMID- 1385299
TI  - The human APO-1 (APT) antigen maps to 10q23, a region that is syntenic with mouse
      chromosome 19.
AB  - The APO-1 (APT) antigen is a cell surface antigen expressed on a variety of
      normal and malignant cells. Binding of anti-APO-1 antibody to the APO-1 antigen
      induces programmed cell death (apoptosis). The APO-1 antigen shows homology to
      the members of the tumor necrosis factor receptor/nerve growth factor receptor
      superfamily. Using cosmid DNA containing the APO-1 gene as a probe for
      fluorescence in situ hybridization, we have mapped the gene to a subregion of
      chromosomal band 10q23. The human APO-1 locus lies within a conserved synteny
      segment present on mouse chromosome 19 consistent with the previous chromosomal
      assignment of the corresponding mouse antigen.

PMID- 1385298
TI  - Synteny mapping in the bovine: genes from human chromosome 5.
AB  - In an effort to generate a more complete bovine syntenic map of Type I
      comparative anchor loci, seven homologs to genes found on HSA5 were mapped using
      a panel of bovine x rodent hybrid somatic cells. Five HSA5 genes, CSF2, RPS14,
      PDGFRB, FGFA, and CSF1R, were assigned to bovine syntenic group U22 (chromosome
      7), while two others, C9 and HGMCR, mapped to U10 and U5, respectively. Previous
      studies had assigned the HSA5 marker SPARC to bovine syntenic group U22. The
      mapping of genes spanning the length of HSA5 in cattle and also in mouse permits
      syntenic comparisons between prototypic genomes of three mammalian orders,
      providing insight into the evolutionary history of this region of the ancestral
      mammalian genome.

PMID- 1385300
TI  - Linkage relations between A2M, HOX3, INT1, KRAS2, and PAH on bovine chromosome 5.
AB  - There is a high level of conservation between human chromosomes and bovine
      syntenic groups. One such comparison is between human chromosome 12 and bovine
      chromosome 5, where at least 16 loci have been shown to be conserved in an
      homologous segment. However, the degree of conservation of order of the loci on
      bovine chromosome 5 is unknown, and in general the conservation of order in
      comparisons between humans and cattle can only be speculated. We have estimated
      the recombination fractions between five of the loci that were previously
      published as mapping to bovine chromosome 5 by a combination of in situ
      hybridization and analysis of bovine-rodent somatic cell hybrid lines to
      determine whether order has been conserved in the homologous segment of bovine
      chromosome 5 and human chromosome 12. Recombination fractions were estimated in
      reference pedigrees of cattle. The loci were A2M, GSNL, HOX3, INT1, KRAS2, and
      PAH. Restriction fragment length polymorphisms for all loci were defined by
      screening a panel of eight restriction endonucleases. The linkage between loci
      was estimated using the lod score method, and all possible pairwise comparisons
      were made. A preliminary map was created by joining together loci that showed the
      smallest recombination fractions and the largest lod scores. A multipoint
      analysis was performed to estimate support for the most likely order. This order
      shows the relative inversion of some of the loci. Moreover, the distance spanned
      in cattle is less than a quarter the distance spanned in humans. Together, these
      data indicate that several chromosomal evolutionary events have occurred in the
      homologous segment shared by humans and cattle.

PMID- 1385301
TI  - Characterization of the human kallikrein locus.
AB  - The human kallikrein gene family is composed of three members: tissue kallikrein
      (KLK1), prostate-specific antigen (PA or APS), and human glandular kallikrein-1
      (hGK-1 or KLK2). The three genes have previously been isolated and mapped to
      chromosome 19q13.2-q13.4. Further analysis of an area of 110 kb surrounding the
      kallikrein genes by CHEF electrophoresis and chromosome walking showed clustering
      of the three genes. The KLK1 gene is positioned in the opposite orientation of
      the APS and KLK2 genes in the order KLK1-APS-KLK2. The APS and KLK2 gene are
      separated by 12 kb; the distance between KLK1 and APS is 31 kb. A CpG island was
      detected in the region between KLK1 and APS. Preliminary data indicate that this
      CpG island is located directly adjacent to a gene that is unrelated to the
      kallikreins and seems to be ubiquitously expressed.

PMID- 1385302
TI  - Homologous chromosomal locations of the four genes for inter-alpha-inhibitor and
      pre-alpha-inhibitor family in human and mouse: assignment of the ancestral gene
      for the lipocalin superfamily.
AB  - The inter-alpha-inhibitor (I alpha I) and pre-alpha-inhibitor (P alpha I) family
      is composed of three plasma protease inhibitors, I alpha I, P alpha I, and
      bikunin, whose chains are encoded by a set of three evolutionarily related heavy
      (H) chain genes designated H1, H2, and H3 and a fourth gene, the so-called alpha
      1-microglobulin/bikunin precursor (AMBP) gene. The latter codes for a precursor
      that splits into: (i) alpha 1-microglobulin, which belongs to the lipocalin
      superfamily; and (ii) bikunin, which is made up of two tandemly arranged protease
      inhibitor domains and belongs to the superfamily of Kunitz-type protease
      inhibitors. The bikunin chain is found in I alpha I and P alpha I molecules and
      it is also present as a free molecule in plasma. In human, the AMBP and H2 genes
      have been mapped to 9q32-q34 and 10p14-p15, respectively, while the H1 and H3
      genes are tandemly located at 3p21.1-p21.2. In situ hybridization mappings
      indicate that the mouse AMBP gene (Intin-4) is located at 4C1----C4, and the H1
      (Intin-1) and H3 (Intin-3) genes are colocated at 14A2----C1. In interspecific
      backcrosses (C57BL/6Pas x Mus spretus) a TaqI restriction variant in (and/or
      near) the H2 (Intin-2) gene identified a linkage of this gene with other
      polymorphic loci, which assigns Intin-2 to the centromeric area of chromosome 2.
      All such assignments are in conserved chromosomal regions between human and
      mouse. Therefore the genetic events that gave rise to the four I alpha I family
      genes took place prior to the divergence between human and mouse.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1385303
TI  - The gene for human transition protein 2: nucleotide sequence, assignment to the
      protamine gene cluster, and evidence for its low expression.
AB  - We have isolated the gene for transition protein 2 (TNP2) from a human cosmid
      clone that contains the genes for protamines 1 and 2. A nucleotide sequence of
      1776 bp that comprises 268 bp of the 5'-noncoding region, 400 bp of exon 1, 849
      bp of an intron, 17 bp of exon 2, and 242 bp of the 3'-noncoding region was
      determined. A modified CAT box, a TATAA box, and two possible polyadenylation
      sites were identified. Transcripts in testicular RNA could be detected only by RT
      PCR and RNase protection assays. By direct sequencing of the PCR products, a cDNA
      sequence was established. It can be deduced from these results that, in contrast
      to other mammalian genes, the human TNP2 gene is expressed at a very low level.
      The human gene differs from that of other mammalian species by the absence of a
      conserved GCCATCAC nucleotide sequence in the 3'-untranslated region. Since both
      protamine genes are known to be localized on chromosome 16p13.3, this chromosomal
      localization holds true for the human TNP2 gene as well. The genes for both
      protamines and TNP2 are arranged in a DNA stretch of 13 kb.

PMID- 1385304
TI  - Analysis of the human cysteine-rich protein gene (CSRP), assignment to chromosome
      1q24-1q32, and identification of an associated MspI polymorphism.
AB  - The human cysteine-rich protein (hCRP) is encoded by a highly conserved and
      widely expressed serum-inducible immediate early response gene. hCRP contains two
      copies of the "LIM/double zinc-finger" motif. Using a characterized hCRP cDNA
      probe, we demonstrate that the human CRP gene (CSRP) is present in a single copy
      and that both mouse and human genomes contain one or more CRP-related genes
      detected by hybridization at low stringency. Using a panel of human x rodent
      somatic cell hybrids, the hCRP locus is assigned to chromosome 1. In situ
      hybridization of 3H-labeled CRP cDNA to human metaphase chromosomes confirms this
      assignment and permits regional localization to bands 1q24-1q32. A common MspI
      polymorphism is identified and mapped to intron 4 of the hCRP gene. The
      chromosomal localization and restriction site polymorphism should prove useful in
      future studies of the function of this gene.

PMID- 1385306
TI  - Chromosomal mapping of human cytokeratin 13 gene (KRT13).
AB  - In the present study the human cytokeratin 13 gene (KRT13), encoding a
      polypeptide characteristic of internal stratified epithelia, has been mapped with
      the help of the polymerase chain reaction and somatic cell hybrids to chromosome
      17. In situ hybridization of a KRT13 cDNA probe to metaphase chromosomes allowed
      the assignment of the KRT13 gene within the q12-q21.2 region of chromosome 17.

PMID- 1385305
TI  - Mapping of the shortest region of overlap of deletions of the short arm of
      chromosome 9 associated with human neoplasia.
AB  - Deletions of the short arm of chromosome 9 with a minimum region of overlap at
      band 9p22 are frequently observed in acute lymphoblastic leukemia and in gliomas.
      They also occur at a lower frequency in lymphomas, melanomas, lung cancers, and
      other solid tumors. These deletions often include the entire interferon (IFN)
      gene cluster, which comprises about 26 interferon-alpha (IFNA), -omega (IFNW),
      and-beta-1 (IFNB1) interferon genes, as well as the gene for the enzyme
      methylthioadenosine phosphorylase (MTAP). By comparing microscopic deletions with
      the genes lost at the molecular level, we have determined the order of these
      genes on 9p to be telomere-IFNB1-IFNA/IFNW cluster-MTAP-centromere. In a few cell
      lines and in primary leukemia cells, we have observed deletions that have
      breakpoints within the IFN gene cluster and result in partial loss of the IFN
      genes. These partial deletions allowed us to determine the order of some genes or
      groups of genes within the IFNA/IFNW gene cluster. Our current results map the
      shortest region of overlap of these deletions in the various tumors to the region
      between the centromeric end of the IFNA/IFNW gene cluster and the MTAP gene
      locus.

PMID- 1385307
TI  - The hypervariable DXS255 locus contains a LINE-1 repetitive element with a CpG
      island that is extensively methylated only on the active X chromosome.
AB  - The DXS255 locus at Xp11.22 is highly polymorphic due to a 26-bp variable number
      of tandem repeats (VNTR) motif. In previous studies, one of the MspI sites
      flanking the VNTR manifested a correlation between methylation and X chromosome
      inactivation. Here we show, by DNA sequence analysis, that this MspI site is
      located within the CpG island at the 5' end of a LINE-1 element, which is 2.5 kb
      from the VNTR. The methylation status of the CpG island was assessed in Southern
      blotting experiments using the methylation-sensitive enzymes HpaII, HhaI, and
      BssHII. All these sites were completely methylated on active X chromosomes,
      consistent with previously reported findings of full methylation of LINE-1
      elements throughout the genome. However, on inactive X chromosomes these sites
      were predominantly unmethylated, although patterns were found to be
      heterogeneous. The results suggest that LINE-1 elements on the inactive X
      chromosome are not suppressed by full methylation of their CpG islands. The
      differential methylation of the DXS255 CpG island provides the basis for a highly
      informative X inactivation analysis system.

PMID- 1385308
TI  - Localization of brain nitric oxide synthase (NOS) to human chromosome 12.
AB  - Recent research has shown that nitric oxide is a novel neuronal second messenger
      and transmitter that may be involved in neuronal cell death and damage in
      neurological illness. To map the chromosomal localization of this important brain
      enzyme, a rat cDNA probe was prepared by RNA PCR from rat cerebellum RNA. This
      rat cDNA was used to isolate a human nitric oxide synthase (NOS) cDNA from a
      human cerebellum cDNA library. The human cDNA clone containing 1.2 kb of brain
      NOS cDNA was hybridized to Southern blots containing DNAs obtained from human
      rodent hybrid cell line panels using EcoRI and HindIII digestion to ascertain the
      location of the human NOS gene. These data showed that the human brain nitric
      oxide synthase mapped within 12q14-qter on human chromosome 12.

PMID- 1385309
TI  - Assignment of the human Fas antigen gene (Fas) to 10q24.1.

PMID- 1385310
TI  - Over-expression and characterization of recombinant beta subunit of the human
      chorionic gonadotropin hormone synthesized in insect cells infected with a
      genetically engineered baculovirus.
AB  - A recombinant baculovirus, vAc beta hCG, having a replacement of the viral
      polyhedrin gene with the cDNA encoding the beta subunit of hCG was used to
      express beta hCG, an extensively glycosylated hormone, in insect cells. Virus
      infected cells, 72 hr pi, secreted approximately 8.02 micrograms beta hCG/2 x
      10(6) cells/ml. The recombinant beta hCG purified from insect cells exhibited
      increased mobility on SDS-PAGE as compared to authentic urinary beta hCG, a
      reflection on differences in glycosylation between insect and mammalian systems.
      The insect derived beta hCG, however, was identical to the native hormonal
      peptide in terms of immunoreactivity and bioactivity on association with alpha
      subunit, as evident by its binding to rat testicular receptors and induction of
      steroidogenesis in a mouse Leydig cell bioassay system. The implications of using
      the baculovirus system to study the importance of carbohydrates for biological
      activity are also discussed.

PMID- 1385311
TI  - Functional relationship between high-affinity E receptor and CD2-11.3 epitope.
AB  - The expression of both high-affinity E receptor (EhR) to sheep erythrocytes and
      CD2-11.3 epitope on activated human T lymphocytes suggests that these two
      structures may be functionally identical or closely associated. Therefore the aim
      of the present work was to determine if the CD2-11.3 epitope is involved in the
      early E rosette formation. The ability of normal and phytohaemagglutin (PHA)
      activated human T lymphocytes to express the CD2-11.3 epitope and to form early E
      rosettes (T cells with EhR) was studied simultaneously. The partial divergence of
      CD2-11.3 expression on T lymphocytes from the ability of these cells to form
      early E (Ee) rosettes was found. The results indicated that the expression of CD2
      11.3 epitope alone is insufficient to form the Ee rosettes by activated T
      lymphocytes, yet it may facilitate this phenomenon in the presence of EhR. The
      above data clearly show that the CD2-11.3 epitope is functionally closely
      associated although not identical to EhR. Accordingly, it seems that these two
      structures may co-adhere to the appropriate ligand. Thus it is possible that the
      CD2-11.3 epitope, as well as its established role in activation signalling, may
      also act as a co-adhesion molecule.

PMID- 1385313
TI  - L-selectin expression differentiates T cells isolated from different lymphoid
      tissues in cattle but does not correlate with memory.
AB  - L-selectin (LECAM-1, LAM-1) was expressed by a high proportion of CD4+ and CD8+ T
      cells, as well as almost all of the gamma delta T-cell receptor (TcR)+ (WC1+) T
      cells, isolated from blood, lymph nodes or tonsils. CD4+ T cells in the lamina
      propria of the gut villi and CD8+ T cells in the villous epithelium as well as
      the majority of WC1+ T cells in the gut mucosa were L-selectin-. The proportion
      of T cells from Peyer's patches that synthesized the molecule was intermediate
      between the value for blood and gut mucosa. Expression of L-selectin therefore
      marks T cells in cattle with a distinct tissue distribution that correlates with
      its function as the peripheral node homing receptor. The proportion of CD4+ and
      CD8+ T cells in the circulation that were L-selectin+ decreased with age. Unlike
      CD45R, expression of L-selectin was not related to CD4 T-cell memory as judged by
      proliferation in transformation assays to soluble antigen. Three-colour
      immunofluorescent staining demonstrated four subpopulations of CD4 and CD8 T
      lymphocytes in peripheral blood mononuclear cells (PBMC) that were CD45R+, L
      selectin+; CD45R+, L-selectin-; CD45R-, L-selectin+; CD45R-, L-selectin-. CD4(4)
      memory cells were CD45R- and L-selectin+ or L-selectin-. Taken with earlier
      studies the reported observations demonstrated that only one of the four
      phenotypes of the CD4+ T cells in blood is present in the lamina propria of the
      gut villi and these are CD45R-, L-selectin-. Two of the four phenotypes of CD8+ T
      cells were present in the gut epithelium; these were CD45R+, L-selectin- or CD45R
      , L-selectin-. Expression of the bovine molecule was not rapidly down-regulated
      on T cells following activation by exposure to phorbol myristate acetate.

PMID- 1385312
TI  - Analysis of thymic stromal cell subpopulations grown in vitro on extracellular
      matrix in defined medium. IV. Cytokines secreted by human thymic epithelial cells
      in culture and their activities on murine thymocytes and bone marrow cells.
AB  - In previous reports we described our approach to the cultivation of murine and
      human thymic epithelial cells in primary cultures, using defined, serum-free
      growth factor-supplemented medium and extracellular matrix-coated culture plates.
      The cells in these cultures displayed high metabolic activity and their
      supernatant was highly active on thymocytes. In the study reported here we
      analysed cytokine activities in the supernatant of human thymic epithelial cell
      cultures (HTES), by using the respective cytokine-dependent cell lines and by
      neutralization with specific monoclonal antibodies. Three cytokine activities
      were detected--interleukin-6 (IL-6), granulocyte colony-stimulating factor (G
      CSF) and macrophage (M)-CSF. Other cytokine activities tested for [IL-1, IL-2, IL
      7, interferon (IFN) and tumour necrosis factor (TNF)] were negative. The effect
      of HTES on concanavalin A (Con A)-induced proliferation of murine thymocytes
      could be completely abolished by anti-IL-6 antibodies, but not by antibodies to
      CSF, whereas enhancement of bone marrow cell proliferation by HTES was partially
      inhibited by either anti-G-CSF or anti-M-CSF antibodies and completely inhibited
      by both antibodies, but not at all by anti-IL-6. We can thus distinguish between
      thymocyte-related cytokines (IL-6) and bone marrow (myeloid/monocyte) related
      ones (G-CSF, M-CSF) in HTES.

PMID- 1385314
TI  - Feeding neonatal rats with IgG antibodies leads to humoral hyporesponsiveness in
      the adult.
AB  - Feeding monoclonal IgG2a or IgG1 anti-horseradish peroxidase (HRP) antibodies to
      12-16-day-old neonatal rats caused a profound suppression of the humoral anti-HRP
      response in these rats as adults. The hyporesponsiveness to HRP was specific and
      long-lasting (up to 5 months). It was shown to be dose dependent, requiring
      relatively large doses of IgG (100-600 micrograms) for maximum effect. Secondary
      IgG (IgG1, IgG2a and IgG2b) responses were most depressed. The effect could be
      reproduced by i.p. injection of antibody. Hyporesponsiveness was not attributable
      to circulating antiidiotype antibodies directed against the monoclonal IgG, nor
      to the continued presence of the monoclonal anti-HRP since rats receiving
      antibody at or some weeks after the time of weaning and gut 'closure' responded
      well to subsequent HRP challenge. The effect was thus dependent on IgG
      administered over the identical period during which the neonatal circulation is
      rich in maternal IgG supplied via the milk. A direct function for maternal IgG in
      moulding the immune repertoire of the offspring, as well as providing passive
      protection, is suggested by these results.

PMID- 1385315
TI  - Antibody responses to non-immunogenic synthetic peptides induced by co
      immunization with immunogenic peptides.
AB  - Chimeric peptides comprising B- and T-helper cell epitopes from the proteins of
      infectious agents represent immunogens with potential for use as new vaccines.
      However, it has become clear that the orientation of the epitopes, the presence
      of spacer residues and the number of copies of the epitopes influence the
      specificity, levels and affinity of the antibody produced following immunization
      with such constructs. Furthermore, the response to peptides is under genetic
      control leading to major histocompatibility complex (MHC)-linked non
      responsiveness. In this study, we have investigated the potential of co
      immunization of immunogenic peptides (to provide T-cell help) with non
      immunogenic peptides (representing B-cell epitopes) to overcome the non-response
      to the latter. For this purpose, we have employed peptides representing T- and B
      cell epitopes derived from the sequences of the fusion and haemagglutinin
      glycoproteins of measles virus. The results obtained show that simple co
      immunization of a B-cell epitope with a T-cell epitope results in the production
      of antibody to the B-cell epitope without the requirement for covalent linkage of
      the two peptides. This approach could thus be used to overcome the problem of
      poor immunogenicity of peptides and will be of potential value in the design of
      immunization strategies using synthetic immunogens.

PMID- 1385317
TI  - Characterization of the C-terminal region of a Trypanosoma cruzi 38-kDa ribosomal
      P0 protein that does not react with lupus anti-P autoantibodies.
AB  - A Trypanosoma cruzi cDNA lambda gt11 recombinant, C-P0, encoding the
      carboxyterminus of a highly antigenic ribosomal P protein, was isolated. Sequence
      comparisons and immunological evidence allowed its identification as the C
      terminal region of the T. cruzi 38-kDa ribosomal P0 protein. This recombinant
      failed to react with systemic lupus erythematosus (SLE) anti-P antibodies. The T.
      cruzi ribosomal P0 protein is the first reported eukaryotic ribosomal P protein
      presenting this immunological property, probably due to its peculiar C-terminal
      amino-acid sequence, FGMGALF, which differs from the conserved eukaryotic
      ribosomal P protein C-terminal consensus, MGFGLFD.

PMID- 1385316
TI  - Mycobacterial 65,000 MW heat-shock protein shares a carboxy-terminal epitope with
      human epidermal cytokeratin 1/2.
AB  - Molecular mimicry between mycobacterial heat-shock protein (hsp) 65 and host
      tissue antigens have been implicated in the autoimmune pathogenesis of certain
      idiopathic diseases. Here, we demonstrated that two of our previously
      characterized monoclonal antibodies (mAb), Ne5 and Nd4 that were directed to a
      carboxy-terminal epitope on the mycobacterial hsp 65, specifically cross-reacted
      with suprabasal cytokeratin of the normal human skin. These mAb also showed
      similar keratin staining of hair follicle epithelia and produced no reaction with
      other dermal components. Both mAb strongly stained the cytoplasm of the majority
      of freshly isolated epidermal keratinocytes from the normal human skin. None of
      these mAb showed staining with human HeLa cells and with human skin fibroblasts.
      Immunoblotting using total keratin extract prepared from isolated epidermal
      keratinocytes revealed that mAb Ne5 and Nd4 specifically reacted with a molecular
      size of 65,000-67,000 MW keratin protein(s) and such reactivity was not observed
      from cytoskeletal proteins extracted from HeLa cells and skin fibroblasts.
      Comparison of immunoblotting reactivity with conventional anti-cytokeratin mAb
      further revealed that mAb Ne5/Nd4 recognized a 65,000-67,000 MW molecular-sized
      protein corresponding to cytokeratin 1/2 from the same keratinocyte extract as
      anti-cytokeratin mAb. Preincubation of mAb Ne5/Nd4 with the purified
      mycobacterial hsp 65 abolished this keratin cross-reactivity in both
      immunohistochemistry and immunoblotting. Moreover, these mAb showed no keratin
      staining in lesional psoriatic skin and also reacted weakly with cultured
      epidermal keratinocytes. Since mAb Ne5/Nd4 specifically recognized a 67,000
      65,000 MW molecular-sized protein(s) derived from epidermal keratinocytes and the
      known characteristics of epidermal cytokeratin 1/2 appeared to be consistent with
      present results, we concluded that Ne5/Nd4 cross-reactive protein(s) in the human
      epidermis is suprabasal cytokeratin 1/2. Comparison of the previously mapped
      Ne5/Nd4 epitope region of amino acid residues 525-540 of the mycobacterial hsp 65
      with the entire sequence of human 65,000 MW keratin revealed that a stretch of
      nine amino acids of the Ne5/Nd4 epitope sequence resembled certain regions of the
      carboxy-terminus of the human 65,000 MW keratin. This similarity of the
      mycobacterial hsp 65 probably contributes to the cytokeratin cross-reactive
      epitope. Our results presented here demonstrate direct evidence of immunological
      cross-reactivity between mycobacterial hsp 65 and human epidermal cytokeratin
      1/2. We speculate that Ne5/Nd4 cross-reactive epitope of epidermal cytokeratins
      might be an important target for skin diseases.

PMID- 1385318
TI  - Immune response to a single peptide containing an immunodominant region of
      hepatitis C virus core protein: the isotypes and the recognition site.
AB  - We have used one single peptide covering the 17 N-terminal amino acids of the
      hepatitis C virus (HCV) core protein (c) to analyse the human immune response
      against B-cell epitope(s) within this region. The sequence MSTNPKPQRKTKRNTNR was
      obtained from two sequenced HCV genomes, and the peptide was synthesized by a
      newly developed method. The peptide was assayed with 144 human sera which had all
      been assayed for antibodies to HCV (anti-HCV) using commercial assays. Forty-nine
      sera were found to be positive for anti-HCV using these assays; 40 of these were
      found to be positive with our anti-HCV IgG peptide assay. The class (IgM, IgG)
      and subclass (IgA1, IgG1-4) specific reactions were determined using the
      polyclonal and monoclonal anti-HCV peptide enzyme immunoassays. Isotypes of
      mainly IgG1 and IgG3, but also IgG4, IgM and IgG2, gave specific reactions with
      this region. Using omission peptide analogues of the region 1-18, the sequence
      RKTKRNTN within residues 9-16 was common to 34 out of 37 sera of which the IgG
      antibody binding site could be mapped. It is unusual for a single peptide assay
      to have such high sensitivity since B cell epitopes within a protein are often
      discontinuous. It seems that at least 80% of HCV infected individuals develop
      antibodies of various isotypes to the antigenic site RKTKRNTN, located in the N
      terminal portion of the HCV core. Thus, the immune response to this peptide
      should be further investigated with regard to the reactive Ig isotypes developing
      during HCV infection.

PMID- 1385319
TI  - Intracellular expression of CD1 molecules on PHA-activated normal T lymphocytes.
AB  - In this study we have analyzed, using immunoperoxidase (IPx) and indirect
      immunofluorescence (IIF), the intracellular and cell surface expression of CD1
      antigens on PHA activated human T cells. By IIF, CD1 isotypes were not detected
      on the surface of 3 days PHA activated cells. Conversely, CD1a, CD1b and CD1c
      molecules were found by IPx in the cytoplasm of normal activated cells from 13
      different donors. Kinetic studies showed that, while CD25 was already observed 24
      h after activation, all 3 isotypes of CD1 molecules started to be detected 48 h
      after PHA activation, with a peak expression at 72 h.

PMID- 1385320
TI  - GM-CSF and G-CSF stimulate the synthesis of histamine and putrescine in the
      hematopoietic organs in vivo.
AB  - Histamine and putrescine (a precursor of polyamines) are formed by histidine
      decarboxylase (HDC) and ornithine decarboxylase (ODC), respectively. Within a few
      hours after injection of a lipopolysaccharide (LPS) into mice, HDC is induced in
      the liver, spleen, lung and bone marrow, and ODC is induced in the liver, spleen
      and bone marrow. Since LPS is known to stimulate the production of various
      cytokines, the abilities of various cytokines to induce HDC and ODC in the
      tissues of mice were examined. IL-2, IL-6, IL-8, IFN gamma and M-CSF were
      ineffective. IL-1 alpha, IL-1 beta, TNF alpha and TNF beta induced HDC and ODC,
      as does LPS. On the other hand, GM-CSF and G-CSF induced HDC and ODC only in the
      spleen and bone marrow within a few hours after their injection. These results
      suggest that, in addition to their roles in inflammation or immune responses, HDC
      and ODC are also involved in an early stage of hematopoiesis.

PMID- 1385321
TI  - The antigen-specific induction of normal human lymphocytes in vitro is down
      regulated by a conserved HIV p24 epitope.
AB  - Synthetic peptides containing amino acid sequence 218-238 of the core protein p24
      of human immunodeficiency virus type 1 (HIV-1) and progressively shorter
      sequences at its C-terminus, were tested for their effect on antigen dependent in
      vitro responses of peripheral blood lymphocytes (PBL) from normal human donors. A
      peptide as short as 7 amino acids, corresponding to a highly conserved sequence,
      was able to inhibit in a dose-dependent manner the induction of a specific
      primary antibody response to the sheep red cell (SRC) antigen, as well as the
      proliferative response to recall microbial antigens. The results of this study
      constitute additional evidence of the immunoinhibitory effects of HIV components
      and may help to unravel some of the pathogenic mechanisms of AIDS. Moreover, they
      are of potential relevance for the development of immunoprophylactic and
      therapeutic strategies.

PMID- 1385322
TI  - Localization of an immunoinhibitory epitope of the cysteine proteinase, cathepsin
      L.
AB  - Antibodies, raised in chickens (IgY) and rabbits (IgG) against the lysosomal
      proteinase cathepsin L, targeted the enzyme in an ELISA and Western blot. In
      contrast to the rabbit IgG, the chicken IgY was immunoinhibitory towards
      cathepsin L. An epitope that elicits immunoinhibitory antibodies has been
      localized to an active site-associated peptide sequence. The corresponding free
      peptide, coated down in an ELISA, is recognised by the chicken IgY, but not the
      rabbit IgG. This peptide was able to inhibit the immunoinhibition of cathepsin L
      by chicken anti-cathepsin L IgY, suggesting its complete or partial identity with
      an immunogenic epitope for chickens in whole cathepsin L.

PMID- 1385324
TI  - Epidemiology of hepatitis C--more lessons to be learnt.

PMID- 1385323
TI  - Determination of epitope specificities of a large number of monoclonal antibodies
      by solid-phase mutual inhibition assays using biotinylated antigen.
AB  - A generally applicable method for the determination of the epitope specificities
      of a large number of monoclonal antibodies (MAbs) is presented. The method is
      based on the solid-phase mutual inhibition assay using 96-well plates coated with
      the respective MAbs, competitor MAbs, biotinylated antigen and avidin-peroxidase
      conjugate. Using carcinoembryonic antigen (CEA) as a model antigen the method was
      applied to the determination of epitope specificities of anti-CEA MAbs. A
      constant amount of biotinylated CEA was incubated with a given MAb immobilized on
      wells of 96-well plates in the presence of increasing amounts of soluble
      competitor MAbs. The biotinylated CEA bound to the immobilized antibody were then
      reacted with avidin-peroxidase conjugate and the activity of the bound peroxidase
      was determined by the use of o-phenylenediamine and hydrogen peroxidase. The
      method used here alleviates the laborious procedures of labeling all antibodies
      to be tested and the confusion caused by differential labeling among different
      MAbs, and is convenient for mapping analysis of many MAbs if the corresponding
      purified antigen is available.

PMID- 1385325
TI  - Palliative segment III biliary bypass (left cholangio-jejunostomy) in malignant
      block at porta hepatis.
AB  - Segment III cholangio-enteric anastomosis was performed in 17 patients with
      obstructive jaundice due to unresectable malignancies at the porta hepatis. The
      operative mortality was 6% (1/17) and morbidity 30% (5/17). More than 50% fall in
      bilirubin level with symptomatic improvement in pruritus was seen in 13 patients.
      Three patients had 25%-50% fall in bilirubin level. This procedure is safe and
      effective in palliation of unresectable hilar obstruction.

PMID- 1385326
TI  - Species-specific mechanisms of carcinogenesis.

PMID- 1385327
TI  - Increased transcripts for B-type natriuretic peptide in spontaneously
      hypertensive rats. Quantitative polymerase chain reaction for atrial and brain
      natriuretic peptide transcripts.
AB  - The cardiac natriuretic peptide family includes atrial natriuretic factor and
      brain or B-type natriuretic peptide, also known as iso-atrial natriuretic factor
      (isoANF). Although these peptides contribute to cardiovascular homeostasis, their
      respective roles remain unclear. To study regulation of atrial natriuretic factor
      and isoANF gene expression during progression of hypertension, we developed a
      quantitative polymerase chain reaction protocol to measure their transcript level
      in spontaneously hypertensive rat (SHR) hearts. At the onset of hypertension,
      atrial natriuretic factor transcripts in 5-week-old SHR were 50% of those of age
      matched Wistar-Kyoto (WKY) rats, whereas the level of isoANF transcripts was
      similar in atria and twofold higher in ventricles. Because atria are the major
      sites of atrial natriuretic factor gene expression and ventricles contribute
      predominantly to cardiac isoANF synthesis, total atrial natriuretic factor
      messenger RNA (mRNA) in the hearts of 5-week-old SHR was about 50% of that in WKY
      rats, and total isoANF mRNA content was already higher than in control rats. In
      left ventricles and ventricular septa, progression of hypertension led to a
      maximal increase of twofold and fourfold in atrial natriuretic factor and isoANF
      mRNA levels, respectively, with no detectable change in right ventricles. In the
      atria of older SHR, atrial natriuretic factor and isoANF mRNA levels were
      comparable to those of age-matched controls. These data indicate that, although
      increased blood pressure stimulates both atrial natriuretic factor and isoANF
      gene expression, regulation of the two natriuretic peptide genes is not
      temporally coordinated in all cardiac compartments. Furthermore, isoANF mRNA is
      already induced in the ventricles at the onset of the hypertensive stage, and in
      older SHR, the isoANF gene is hyperresponsive to progression of hypertension
      compared with atrial natriuretic factor. Thus, isoANF might represent a very
      sensitive marker of cardiac changes in hypertension.

PMID- 1385329
TI  - Effect of substance P and somatostatin on migration of polymorphonuclear (PMN)
      cells in vitro.
AB  - The effects of the two neuropeptides, substance P (SP) and somatostatin (SOM), on
      the migration of polymorphonuclear cells derived from 13 volunteers were
      investigated. The neuropeptides were applied in concentrations between 10(-12)
      and 10(-6) M. Only at a concentration of 10(-6) M SP did the chemotaxis of PMN
      cells increase slightly but statistically significantly. In contrast to SP, SOM
      showed a significant dose-dependent stimulation of chemotaxis, which was first
      traceable at 10(-10) M and increased up to 10(-6) M. Although it is uncertain
      whether in vivo SP and SOM contribute directly to the invasion of PMN cells into
      the joint cavity, the influence of these neuropeptides on PMN migration in vitro
      is a further indication of the neuropeptide involvement in the genesis of
      inflammation.

PMID- 1385328
TI  - Transthyretin is an inhibitor of monocyte and endothelial cell interleukin-1
      production.
AB  - Human serum was found to contain an inhibitor of constitutive interleukin-1 (IL
      1) production by human umbilical vein endothelial cells (ECs). Purification of
      the serum activity by anion exchange chromatography, molecular sieve HPLC, and
      hydroxyl apatite chromatography yielded material 82% pure with a molecular weight
      of 17 kDa by SDS-PAGE. Amino acid sequencing revealed the purified inhibitor to
      be transthyretin (TTR), a liver-derived protein. There was a 42.6% reduction in
      the production of spontaneous IL-1 activity in EC supernatants after coculture
      with 10 micrograms/ml TTR. TTR was subsequently found by ELISA to inhibit LPS
      stimulated IL-1 production by cells of the human monocytic leukemia line THP-1 by
      47.1 +/- 9.4%, whereas a less striking but still significant inhibition of
      monocyte-derived IL-1 beta production was also observed. Inhibition of IL-1
      secretion correlated with increased IL-1 mRNA synthesis in both THP-1 cells and
      monocytes. Furthermore, TTR was associated with increased intracellular
      concentrations of IL-1 beta. These data suggest that TTR functions by inhibiting
      processing of newly synthesized peptide for secretion. This novel inhibitory
      effect of TTR on the production of IL-1 activity suggests a previously
      unrecognized endogenous antiinflammatory mediator.

PMID- 1385330
TI  - Cholera in the Americas: an overview.

PMID- 1385332
TI  - Relapsing fever and its serological discrimination from Lyme borreliosis.
AB  - Patients with Borrelia-caused relapsing fever produce cross-reacting antibodies
      to Borrelia burgdorferi, the anti-genetically related causative agent of Lyme
      borreliosis. The antibody response of the serum of a patient (acute and
      convalescent) with relapsing fever was analysed by the immunoblot technique using
      Borrelia hermsii and B. burgdorferi as antigens. The diagnosis was established by
      microscopic detection of spirochetes in the patient's blood. The patient's serum
      showed significantly elevated titers of IgG and IgM in a B. burgdorferi indirect
      immunofluorescence assay. Immunoblot analysis indicated the presence of cross
      reacting antibodies directed to B. burgdorferi antigens with apparent molecular
      weights of 60, 41, 40, 36, 30 and 20 kDa.

PMID- 1385331
TI  - Infrequent detection of HIV-1 components in tears compared to blood of HIV-1
      infected persons.
AB  - Beside the risk of infection via HIV-1-contaminated blood, ophthalmologists are
      especially interested in the possibility of HIV-1 infection via tears. Therefore
      we tried to isolate HIV-1 from tears of 50 HIV-1-infected persons in different
      stages of disease by reverse transcriptase (RT) and by p24-antigen (p24-AG) in
      the cultures. Simultaneously we tried to isolate HIV-1 in the supernatant from
      peripheral blood lymphocytes (PBL), which was successful in 32 of the 50 examined
      specimens. HIV-1 could not be isolated from the tears of these persons. In
      addition, polymerasechain-reaction (PCR) was performed to detect proviral
      sequences (gag, pol, env) of HIV-1 in tears and blood of ten HIV-1-infected
      patients. While in all the examined patients gag, pol and env could be detected
      in the blood samples, only one tear sample was found positive for gag and pol DNA
      fragments. These results indicate that tears of HIV-1-positive contain extremely
      low quantities of tissue culture infectious doses (TCID) of HIV-1 in contrast to
      PBL. HIV-1 infection via tears therefore appears to be unlikely.

PMID- 1385333
TI  - Visceral leishmaniasis complicating chronic hepatitis B treated with interferon.

PMID- 1385334
TI  - Low prevalence of antibodies to hepatitis C virus in hospital employees.

PMID- 1385335
TI  - Expression of different tenascin isoforms in normal, hyperplastic and neoplastic
      human breast tissues.
AB  - Functionally different tenascin (TN) isoforms, containing varying numbers of a 91
      amino-acid motif resembling the fibronectin type-III homology repeat, may be
      generated by alternative splicing of the TN primary transcript. In fact, only the
      TN isoform containing the alternatively spliced region can induce loss of focal
      adhesion in cultured cells and seems to be able to facilitate cell migration. We
      examined the patterns of alternative splicing of the TN primary transcript in
      normal, hyperplastic and neoplastic breast tissues, and found that, in all the
      invasive breast carcinomas analyzed, the relative amount of TN mRNA in which the
      alternatively spliced region was included was about 10 times higher than in RNA
      from normal breast tissues. A similar result was observed in phyllodes tumors and
      in those fibroadenomas which showed very high stromal cellularity. Western-blot
      analysis using different monoclonal antibodies showed the same pattern as that
      seen in Northern blotting. The data reported here suggest that, in the breast,
      expression of the high-molecular-mass TN isoform is a marker of stromal element
      proliferation and that, in invasive breast carcinomas, this TN isoform could play
      a role in generating a permissive environment for proliferation, invasion and
      metastasis of neoplastic epithelial cells.

PMID- 1385337
TI  - Secretion of cell-adhesion-promoting factors, fibronectin, fibronectin fragments
      and a 53-kDa protein, by human rectal adenocarcinoma cells.
AB  - Production of cell-adhesion proteins was examined in 10 cell lines and 5 cultured
      human cancer cells at an early passage. Two-thirds of the tested cells produced
      and secreted into their culture medium variable amounts of material active in
      promoting cell attachment. One of the rectal carcinoma cell lines, CaR-I, grew
      well in serum-free medium and secreted a large amount of the active principle.
      The active principles produced by CaR-I cells were characterized after partial
      purification, and were found to be fibronectin and its fragments. The presence of
      fibronectin and its fragments was proved by the following facts: (1) reactivity
      to the monoclonal antibodies which recognize different epitopes of fibronectin,
      and (2) reactivity to RGD peptide which is the attachment sequence of
      fibronectin. In addition to fibronectin and its fragments, CaR-I cells were also
      shown to produce a 53-kDa attachment factor. Unexpectedly, the protein was proved
      to be most probably the p53 suppressor gene product.

PMID- 1385338
TI  - Atrial premature beats coupling interval determines lone paroxysmal atrial
      fibrillation onset.
AB  - In 20 patients with recurrent episodes of lone paroxysmal atrial fibrillation we
      assessed the onset pattern of each episode of either atrial fibrillation or of
      atrial flutter during a 24-h Holter monitoring. We evaluated 24 twenty-four-hour
      Holter tape recordings and our data are related to 168 episodes of paroxysmal
      atrial fibrillation and 27 episodes of paroxysmal atrial flutter. Eighty-five
      percent of atrial fibrillations and 67% of atrial flutters were of short duration
      (less than 5 min). The majority of patients (80%) had either nocturnal or daily
      episodes of arrhythmia and PP intervals immediately before onset of arrhythmia
      did not show significant variations in 77% of cases. The coupling interval of the
      supraventricular premature beats eliciting atrial fibrillation was significantly
      shorter than the coupling intervals of the spontaneous isolated supraventricular
      premature beats (p less than 0.0001); again, in 6 patients with either atrial
      fibrillation or flutter, the coupling interval at onset of fibrillation was
      significantly shorter in comparison to flutter (p less than 0.0001). In
      conclusion, vagal or sympathetic prevalence does not seem to influence
      significantly the beginning of the arrhythmia, while the coupling interval of the
      atrial premature beats plays a critical role in the inducibility of atrial
      flutter or fibrillation.

PMID- 1385336
TI  - Breast cancer is associated with loss of the c-kit oncogene product.
AB  - The proto-oncogene c-kit encodes a tyrosine kinase receptor related to the
      PDGF/CSF-1 receptors. Mutations of this gene result in impairment of
      hematopoiesis, melanogenesis and gametogenesis. Using monoclonal antibodies to
      the c-kit gene product, we have analyzed its expression in normal and transformed
      human tissues. Unexpectedly, the receptor was found to be expressed in normal
      mammary epithelium. While in benign breast lesions, the c-kit gene product was
      detected at variable levels in 82% of the instances, in primary tumors, no
      product could be identified in 87% of the cases. This phenotype is maintained in
      metastatic foci. These findings were confirmed by paired Northern blot analysis
      of RNA preparations from normal and tumor tissues. These results demonstrate that
      the c-kit receptor may also be involved in the growth control of mammary
      epithelium and that this function may be impaired following malignant
      transformation and de-differentiation.

PMID- 1385339
TI  - Effect of immunosuppressive agents on the guanethidine-induced sympathectomy in
      athymic and euthymic rats.
AB  - Guanethidine sulphate causes destruction of peripheral sympathetic neurons and
      infiltration of mononuclear inflammatory cells in the sympathetic ganglia of both
      athymic nude (rnu/rnu) and euthymic LEW/Mol rats. The effect of guanethidine is
      believed to be an autoimmune reaction. To determine the effect of
      immunosuppressive drugs concurrently with guanethidine treatment both athymic and
      euthymic rats were treated with guanethidine 40 mg/kg i.p. daily for 14 days,
      cyclophosphamide 100 mg/kg i.p. on days 1 and 8, methylprednisolone 10 mg/kg and
      cyclosporin A 10 mg/kg daily from days 1 to 7, and then every other day from days
      8 to 14. The number of neurons in the sympathetic ganglia was counted and four
      subpopulations of mononuclear inflammatory cells were identified by monoclonal
      antibodies MHC II, CD8 T-cells/NK-cells, CD5 T-cells, CD4 T-cells/macrophages.
      Our results show that the immunosuppressive drugs used were unable to prevent the
      guanethidine-induced reduction of sympathetic neurons, although the number, of
      neurons following guanethidine-methylprednisolone treatment was significantly
      higher compared with guanethidine alone in both athymic and euthymic rats. The
      identification of mononuclear cells in the sympathetic ganglia showed that the
      CD8/NK and CD5 populations were the populations primarily responding to
      guanethidine treatment. Both CD8/NK and CD5 populations were absent without
      guanethidine, but increased significantly following guanethidine in both athymic
      and euthymic animals. None of the immunosuppressive drugs used could prevent the
      guanethidine-induced rise in the CD8/NK population in neither athymic nor in
      euthymic rats. The rise in the CD5 population was suppressed following treatment
      with all immunosuppressive drugs in athymic rats, but only following
      methylprednisolone in euthymic animals. These results indicate that guanethidine
      induces proliferation of T-cells in euthymic rats and non-functional CD5 positive
      pre T-cells in athymic animals. The CD5 population in both athymic and euthymic
      animals appears relatively more sensitive to immunosuppressive drugs than the NK
      cell population also activated by guanethidine. This relatively resistant NK-cell
      population seems to play an important role in the guanethidine-induced
      destruction of sympathetic neurons and can explain why the guanethidine-induced
      immunological reaction could not be fully prevented by the immunosuppressive
      drugs used. The conclusion is that guanethidine induces destruction of
      sympathetic neurons by a NK-cell-mediated reaction.

PMID- 1385340
TI  - Identification of childhood disability in Jamaica: evaluation of the ten question
      screen.

PMID- 1385341
TI  - Role of adhesion molecules in the immune reaction to M-MSV-induced tumors.
AB  - We have investigated the in vivo role of 2 different adhesion molecules, LFA-1
      and LECAM-1, in the immune reaction to Moloney-murine-sarcoma-virus(M-MSV)
      induced tumors, which undergo a peculiar spontaneous regression due to generation
      of a strong virus-specific cytotoxic-T-lymphocyte(CTL) response. Repeated
      administration of anti-LFA-1 monoclonal antibody (FD441.8 MAb), i.p. or at the
      site of virus inoculation, enhanced tumor growth and delayed regression, while
      i.p. administration of anti-LECAM-1 MEL-14 MAb gave rise to tumors that grew
      progressively and caused host death. Evaluation of the immunological response in
      MAb-treated mice showed reduced generation of virus-specific CTL precursors (p)
      in the spleen of animals given FD441.8 MAb i.p.; CTLp frequency in locally
      treated mice overlapped with that of control mice injected with virus only.
      FD441.8 MAb treatment did not interfere with CTL homing in the tumor, since the
      frequency of M-MSV-specific CTLps in sarcomas was similar in treated and control
      mice. Cytofluorimetric analysis indicated that the majority of tumor-infiltrating
      lymphocytes (TIL) from MAb-treated mice were covered by anti-LFA-1 MAb, and
      lacked cytotoxic activity when assayed against target cells bearing relevant
      tumor antigens. Instead, in mice injected i.p. with MEL-14 MAb, a very low
      frequency of CTLps was detected in lymph nodes draining the tumor area, and
      within the tumor. Our results indicate that enhanced tumor growth, depending on
      the MAb used, is the resultant of an inhibitory effect on different T-lymphocyte
      functions. Tumor progression in anti-LFA-1 MAb-injected mice is explained mostly
      by blockage of CTL lytic activity at the tumor site; in mice receiving i.p. MEL
      14 MAb treatment, by the failure of naive T lymphocytes to enter peripheral lymph
      nodes and subsequently by the lack of generation of tumor-specific CTLs.

PMID- 1385342
TI  - The influence of oral and subcutaneous administration of a mixed beta-adrenergic
      agonist on tissue and cell growth.
AB  - The non-selective beta-adrenergic agonist, metaproterenol, administered orally (2
      ppm and 20 ppm) and subcutaneously (0.1 mg/Kg/d) for 21 days to young male rats
      induced no changes in animal growth or food intake. However, the rats treated
      with metaproterenol showed increased muscle gastrocnemius weight, which was
      accompanied by a muscle hyperplasia (DNA content increase) and a reduction in
      cellular size (protein/DNA ratio decrease). The beta-agonist did not affect liver
      growth or liver cellularity when assessed through the nucleic acid content. The
      increase in muscle mass was attributed, at least in part, to a reduction in
      protein breakdown as muscular cathepsin A activity was significantly lower in
      beta-agonist treated rats.

PMID- 1385344
TI  - Sequence homology between two immunodiagnostic fusion proteins from Echinococcus
      multilocularis.
AB  - Serological diagnosis of alveolar hydatid disease using crude parasite antigen is
      problematical with the result that several groups have addressed the question of
      specific serodiagnosis using defined native or recombinant antigens. Sequence
      data are available for two lambda gt 11 cDNA clones, designated EM4 and pEM10,
      which express E. multilocularis species-specific proteins in immunodiagnostic
      assays using human sera. Here, we have drawn attention to the extensive
      similarities between these antigens and have compared their characteristics since
      both may prove valuable in the future diagnosis of alveolar hydatidosis.

PMID- 1385343
TI  - Therapy of genital human papillomavirus infections. Part II: Methods of
      treatment.

PMID- 1385345
TI  - Structure activity of C-terminal modified analogs of Ac-CCK-7.
AB  - Previous work indicates that both the C-terminal phenylalanine amide and the
      tryptophan moieties of cholecystokinin (CCK) are critical pharmacophores for
      interaction with either the A or B receptor subtypes. We have examined a series
      of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe33-NH2] (2) in which
      the phenyl ring of the C-terminal Phe-NH2 has been modified. Compounds were
      assessed in binding assays using homogenated rat pancreatic membranes and bovine
      striatum as the source of CCK-A and CCK-B receptors respectively and for
      anorectic activity after intraperitoneal administration to rats. Substitution of
      a number of cycloalkyl or bicyclic aryl moieties for the phenyl ring of
      phenylalanine33 including cyclopentyl (20), cyclohexyl (21), cyclooctyl (23), 2
      (5,6,7,8-tetrahydro)naphthyl (26), 2-naphthyl (27), and 1-naphthyl (29) led to
      analogs with 10-70 times the anorectic potency of 2. The anorectic activity of 21
      was blocked by the specific CCK-A receptor antagonist MK-329. Other bulky
      aliphatic groups in place of the phenylalanine33 aromatic ring such as isopropyl,
      2-adamantyl and cyclohexylmethyl gave derivatives similar to 2 in potency. While
      most of the new compounds were comparable to CCK in binding assays, 23, 26, 27
      and 29 were exceptionally potent with IC50s 10(-11)-10(-14) M in the pancreas.
      Compounds 23 and 29 were further evaluated for their ability to stimulate amylase
      secretion and found to have potencies similar to that of CCK. The dissociation
      between potency in the binding and amylase secretion assays suggests that they
      may interact with a high affinity binding site which is not coupled to amylase
      secretion. We conclude that CCK receptors possess a generous hydrophobic pocket
      capable of accommodating large alkyl groups in place of the side chain of
      phenylalanine33 and that the pharmacological profile of CCK analogs can be
      tailored by appropriate exploitation of this finding.

PMID- 1385347
TI  - Novel version of Multiple Antigenic Peptide allowing incorporation on a cysteine
      functionalized lysine tree.
AB  - A novel version of Multiple Antigenic Peptide (MAP) is described. This approach
      consists of the synthesis of a properly functionalized antigen carrier and the
      incorporation, on request, of one or more activated antigenic peptides. This
      method was to synthesize a MAP containing eight epitopes of Hsp 70-1 from
      Plasmodium falciparum. Mice immunised with this MAP gave a specific response
      while those immunised with the peptide alone did not.

PMID- 1385346
TI  - Proteinase-catalyzed conversion of a substance P-precursor peptide.
AB  - The protease-catalyzed conversion of peptides and proteins produced by
      recombinant DNA technology is a promising method for large-scale production of
      peptides including those with non-proteinogenic structural elements. As a model
      system we have investigated the proteinase-catalyzed modification of a chemically
      synthesized substance P-precursor. In the precursor peptide the residues of
      substance P(1-8) were flanked by tripeptide linkers on both sides. In the first
      step the C-terminal tripeptide amide was replaced by the authentic C-terminal
      tripeptide amide of substance P via alpha-chymotrypsin-catalyzed
      transpeptidation. The enzyme simultaneously attacks two peptide bonds in the
      precursor molecule leading to the formation of several side-products. The desired
      peptide was obtained with 25% yield. In the second step the other tripeptide
      linker was selectively and almost quantitatively removed from the N-terminus of
      the precursor via trypsin-catalyzed hydrolysis. This study demonstrates that
      substance P can be obtained from an engineered protein by proteinase-catalyzed
      processing.

PMID- 1385348
TI  - Bacterial periplasmic permeases as model systems for the superfamily of traffic
      ATPases, including the multidrug resistance protein and the cystic fibrosis
      transmembrane conductance regulator.

PMID- 1385349
TI  - [Anti-arrhythmia agents. Effectiveness, lack of effectiveness and pro-arrhythmia
      effects].

PMID- 1385351
TI  - Simultaneous expression of keratin and glial fibrillary acidic protein by the
      same cells in epiretinal membranes.
AB  - The identification of cells comprising epiretinal membranes is difficult because
      of the phenotypic changes that occur. Examination of intermediate filament
      protein content by immunocytochemical analysis can help to identify some cells
      with altered ultrastructure but is not always definitive because altered
      expression of intermediate filament proteins can also occur. To examine this
      issue further, the authors utilized a postembedding immunocytochemical technique
      with epiretinal membranes in which they were able to double label for keratin, a
      useful marker for identifying retinal pigment epithelial cells, and glial
      fibrillary acidic protein (GFAP), a useful marker for identifying glial cells.
      Nine of ten idiopathic epiretinal membranes contained cells that labeled for GFAP
      and not keratin. Two of these membranes also contained cells that labeled only
      for keratin and one membrane contained cells that simultaneously labeled for both
      GFAP and keratin. Other types of epiretinal membranes had an equal participation
      by cells that expressed only GFAP or keratin (12 of 17 membranes contained cells
      positive for keratin; 13 of 17 contained cells positive for GFAP). Ten of 17
      nonidiopathic membranes contained cells simultaneously expressing GFAP and
      keratin, although they comprised only a minor subpopulation of the total number
      of cells present. These findings demonstrate that keratin and GFAP are not
      mutually exclusive intermediate filament proteins in cells of epiretinal
      membranes and that, although each may provide a helpful adjunct for cell type
      identification, neither is an absolutely specific marker.

PMID- 1385350
TI  - Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix
      metalloproteinases.
AB  - Healing of corneal alkali injuries remains a severe clinical challenge. The
      authors evaluated the effect of a new synthetic inhibitor of matrix
      metalloproteinases (GM6001 or N-[2(R)-2-(hydroxamido carbonylmethyl)-4
      methylpentanoyl]-L-tryptophane methylamide) on preventing ulceration of rabbit
      corneas after alkali injury. Topical treatment of corneas with severe alkali
      injuries with 400 micrograms/ml or 40 micrograms/ml GM6001 alone prevented
      ulceration for 28 days, although 8 of 10 corneas treated with vehicle perforated.
      Corneas treated with 4 micrograms/ml GM6001 had midstromal depth ulcers. Corneas
      treated with 400 micrograms/ml of GM6001 contained very few inflammatory cells
      and had significantly reduced vessel ingrowth compared with vehicle-treated
      corneas. Epithelial regeneration after moderate alkali injuries also was
      investigated. Persistent epithelial defects developed 4 days after moderate
      alkali injury in rabbit corneas treated with vehicle and progressively increased
      to an average of 20% of the original 6 mm diameter wound by 27 days after
      moderate alkali injury. By contrast, epithelial regeneration was complete and
      persisted for 21 days for corneas treated with a formulation containing GM6001
      (400 micrograms/ml), epidermal growth factor (10 micrograms/ml), fibronectin (500
      micrograms/ml), and aprotinin (400 micrograms/ml). Sporadic punctate staining
      developed in 20% of the corneas treated with the combination of agents between
      days 21-28 after moderate alkali injury. These results demonstrate that topical
      application of GM6001 prevented corneal ulceration after severe alkali injury and
      that a combination containing GM6001, epidermal growth factor, fibronectin, and
      aprotinin promoted stable regeneration of corneal epithelium after moderate
      alkali injury.

PMID- 1385352
TI  - Adhesion molecules in experimental phacoanaphylactic endophthalmitis.
AB  - Intraocular accumulation of inflammatory neutrophils is an important feature of
      experimental phacoanaphylactic endophthalmitis (EPE). Increasing evidence
      suggests that localization of neutrophils to the site of inflammation requires
      the participation of neutrophil and endothelial adhesion molecules. These studies
      were undertaken to determine if blocking of adhesion molecules on neutrophils
      (CD18) or endothelium (ELAM-1) could attenuate EPE in Lewis rats. Treatment of
      experimental animals with anti-CD18 or anti-ELAM-1 significantly suppressed
      intraocular neutrophil accumulation, retinal hemorrhage, and vasculitis, and
      attenuated retinal edema formation by 48% and 70%, respectively. These
      observations demonstrate that antibodies directed against adhesion molecules on
      the neutrophil (CD18) or the vascular endothelial cell (ELAM-1) exhibit potent
      anti-inflammatory effects, resulting in a striking amelioration of injury in EPE
      in rats.

PMID- 1385354
TI  - Phase II trial of fazarabine (arabinofuranosyl-5-azacytidine) in patients with
      advanced pancreatic adenocarcinoma.
AB  - We conducted a phase II evaluation of fazarabine 1.75-2.0 mg/m2/hr over 72 hours
      every 28 days in 14 previously untreated patients with advanced adenocarcinoma of
      the pancreas. The initial dose was 1.75 mg/m2/hr in 10 patients, and 2.0 mg/m2/hr
      in 4 patients. The dose was escalated in 8 patients, including all 4 who started
      at the higher dose level. Toxicity was unexpectedly mild. The median WBC nadir
      was 4.4 (range: 2.4-15.8) x 10(3)/microliters, the median absolute neutrophil
      nadir was 3.2 (range: 0.9-13.0) x 10(3)/microliters, and the median platelet
      count was 134.0 (range: 48.0-291.0) x 10(3)/microliters. Gastrointestinal
      toxicity was generally mild. No major responses were seen, excluding, with 95%
      confidence, a response rate in excess of 20%.

PMID- 1385356
TI  - Epitopes at the proteolytic cleavage sites of HIV-1-gp120 and RSV-F protein share
      a sequence homology: comparative studies with virus-induced and antipeptide
      antibodies.
AB  - The proteolytic cleavage sites of the human immunodeficiency virus type 1 (HIV-1)
      envelope glycoprotein precursor gp160 and the fusion protein of respiratory
      syncytial virus (RSV) show a sequence homology. To study this homology two
      synthetic peptides corresponding to HIV-1-env-gp160-aa 507-518 (KAKRRVVQREKR) and
      RSV-F2-aa 130-136 (SKKRKRR) were synthesized. Human serum samples from HIV
      positive or RSV-positive collections recognized the appropriate peptide in 90.6
      or 37.2% respectively. No cross-reactivity towards the nonhomologous peptide
      could be monitored in both serum collections. In contrast, antipeptide antibodies
      raised against both peptides demonstrate a high degree of cross-reactivity. These
      data indicate that the high specificity of the virus-induced antibodies may be a
      result of strong conformational restrictions at the proteolytic cleavage site of
      both proteins. Moreover, these observations are important for diagnostic
      purposes. Synthetic peptides are a valuable tool for HIV antibody screening. Our
      data provide information concerning the specificity of antigen-antibody
      interaction on a highly immunogenic HIV-1 epitope.

PMID- 1385353
TI  - Phase II trial of fludarabine phosphate for adenocarcinoma of the pancreas. An
      Illinois Cancer Center study.
AB  - We have conducted a phase II trial of fludarabine phosphate for advanced
      measurable adenocarcinoma of the pancreas. The drug was administered every 4
      weeks by a daily-times-5 bolus schedule beginning at 20 mg/m2/day. No responses
      were observed in 20 evaluable patients, 18 of whom were previously untreated.
      Dose-limiting toxicity was leukopenia, and gastroenterologic side effects were
      frequent. Life-threatening or fatal renal dysfunction occurred in 3 patients. In
      this schedule fludarabine phosphate is ineffective against adenocarcinoma of the
      pancreas and appears to have unpredictable severe renal toxicity.

PMID- 1385355
TI  - Efficacy of prostate-specific antigen and magnetic resonance imaging in staging
      stage C adenocarcinoma of the prostate.
AB  - OBJECTIVES: The authors compared the two most common presurgical tests now used
      for the preoperative staging of adenocarcinoma of the prostate, prostate-specific
      antigen (PSA) and magnetic resonance imaging (MRI). METHODS: One hundred
      consecutive radical retropubic prostatectomy patients were imaged at 1.5 Tesla
      before surgery with routine T1-weighted and T2-weighted transaxial images. The
      images were analyzed by two experienced radiologists for evidence of
      extracapsular disease. Radiologists rated each gland on a scale of 0 to 100 for
      the percentage likelihood of extracapsular disease based on its MRI appearance.
      Receiver operator characteristic (ROC) curves were plotted, and areas were
      calculated for the two radiologists and the preoperative PSA values. RESULTS:
      Comparison of the areas of the ROC curves generated from the two radiologists and
      those from the preoperative PSA values showed no statistical difference.
      CONCLUSIONS: In this series, radiologic interpretation of body coil MRI studies
      in those patients chosen for a radical retropubic prostatectomy was no better in
      staging adenocarcinoma of the prostate than simply using the preoperative PSA
      values.

PMID- 1385357
TI  - Complement neoantigen and vitronectin are components of plaques in amyloid AL
      neuropathy.
AB  - We studied three patients with late onset, chronic sensorimotor and autonomic
      neuropathy in course of plasma cell dyscrasia with Bence Jones proteinuria.
      Histopathological findings of nerve biopsies consisted in diffuse loss of
      myelinated and unmyelinated fibers associated with perivascular deposits of
      amorphous material with physico-chemical and ultrastructural features of amyloid.
      By immunohistochemistry, light chains of the same type as Bence Jones protein,
      components of the classic and lytic pathways of the complement and vitronectin
      were detected at the level of amyloid nodules. The colocalization of complement
      neoantigen and vitronectin suggests that this complex derives from the
      circulation. The elucidation of the chemical composition of amyloid might shed
      some light in the pathogenesis of these disorders.

PMID- 1385358
TI  - Palliation for the dying.

PMID- 1385359
TI  - [Inguinal hernia as a sequela of disordered bladder emptying?].
AB  - We examined 56 patients with hernias and 49 patients with other diseases prior to
      operation. They were all above 50 years of age. The urological screening
      examination included the patients history of the frequency of urination during
      night and day time, dysuria, the common risk factors (smoking, coughing,
      obstipation), obesity, a sonographic measurement of the prostate diameters, a
      sonographic evaluation of residual urine and the determination of the urinary
      flow rate. None of the above parameters showed a significant difference between
      the two groups. Surprisingly more than 60% of all men showed a pathological
      voiding function (either residual urine and/or a pathological flow rate). Our
      conclusions are: 1. Patients with inguinal hernias do not show a greater
      incidence of pathological bladder function than patients of the control group.
      The benign prostatic hypertrophy as a risk factor for the development of inguinal
      hernias is most questionable. 2. Because the results showed no significant
      difference between the two groups, a determination of residual urine prior to
      operation is not necessary. 3. More than 60% of the men above 50 years showed a
      pathological voiding function. We recommend a urological screening test for all
      men above 50 years of age during hospitalisation.

PMID- 1385360
TI  - Molecular genetic studies in black families with sickle cell anemia and unusually
      high levels of fetal hemoglobin.
AB  - Clinical, hematologic, and molecular genetic studies are reported for five
      families with SS patients having unusually high fetal hemoglobin (Hb F) levels
      (mean 28.3%, range 19-42%). Some of the individuals were symptom-free and one was
      not anemic. However, some were symptomatic despite a very high Hb F. Neither the
      Hb F level nor the F cell distribution entirely explained the variation in
      clinical severity. Molecular genetic studies identified the Senegal haplotype
      with the associated -158 G gamma (C----T) mutation in two of the five families.
      The -202 G gamma (C----G) mutation was not found in any of the individuals
      studied. Sequencing of the gamma-globin gene promoters to detect genetic high F
      determinants not detectable by restriction digestion was not performed. All AS
      parents and AS siblings demonstrated elevated F cells when the Senegal/-158 G
      gamma (C----T) mutation was present with either the beta S or beta A allele.
      Double heterozygosity for two different high F determinants in some SS patients
      is suggested by the studies in at least one family. Discordance among siblings in
      clinical and hematologic manifestations in two families provides additional
      evidence for loci regulating Hb F cell production which are not linked to the
      beta-globin gene clusters.

PMID- 1385361
TI  - A second observation of the fetal methemoglobin variant Hb F-M-Fort Ripley or
      alpha 2G gamma 2(92)(F8)His----Tyr.
AB  - We have identified a second baby with the fetal methemoglobin F-M-Fort Ripley. It
      was observed in a Caucasian infant from Canada; at least eleven additional
      members of that family were known to have had a neonatal cyanosis similar to that
      seen in the propositus and in a previously described baby (2). Sequencing of
      amplified DNA that included (part of) the G gamma gene greatly facilitated the
      characterization. The G gamma X chain was readily isolated by reversed phase high
      performance liquid chromatography; its quantity was approximately 12.5% of total
      gamma. Interestingly, the baby also carried the A gamma T mutation on one
      chromosome, either in cis or in trans to the G gamma X mutation. Hb F-M-Fort
      Ripley could be isolated in reasonably pure form by DEAE-cellulose
      chromatography. The isolated Hb FX was unstable, had spectral changes
      characteristic for the M-hemoglobins, while its methemoglobin derivative reacted
      rapidly with cyanide. Oxygen affinity data could not be obtained. It is suggested
      that the formation of a rather large amount (approximately 25%) of mixed hybrids
      (alpha 2G gamma X.gamma) with low oxygen affinity is the main cause for the
      occurrence of the neonatal cyanosis.

PMID- 1385362
TI  - Detection of genetic variation between and within populations of Gliricidia
      sepium and G. maculata using RAPD markers.
AB  - Gliricidia sepium and G. maculata are multi-purpose leguminous trees native to
      Central America and Mexico. Research programmes have been initiated to define the
      native distribution of Gliricidia and sample the spectrum of genetic variation.
      To date, there has been little systematic assessment of genetic variability in
      multi-purpose tree species. Accurate estimates of diversity between- and within
      populations are considered a prerequisite for the optimization of sampling and
      breeding strategies. We have used a PCR-based polymorphic assay procedure (RAPDs)
      to monitor genetic variability in Gliricidia. Extensive genetic variability was
      detected between species and the variability was partitioned into between- and
      within-population components. On average, most (60 per cent) of the variation
      occurs between G. sepium populations but oligonucleotide primers differed in
      their capacity to detect variability between and within populations. Population
      specific genetic markers were identified. RAPDs provide a cost-effective method
      for the precise and routine evaluation of variability and may be used to identify
      areas of maximum diversity. The approaches outlined have general applicability to
      a range of organisms and are discussed in relation to the exploitation of multi
      purpose tree species of the tropics.

PMID- 1385363
TI  - The current role of prostatic acid phosphatase and prostate-specific antigen in
      the management of prostate cancer.
AB  - Although PSA is considered to be the true serum marker of prostatic tissue and a
      valuable indicator for cancer in the gland, knowledge of its significance and
      limitations is essential to its use for screening, staging, and monitoring CAP.
      PSA may be used in conjunction with DRE for early detection of CAP. Men with
      abnormal DRE should have a TRUS with or without biopsy. In men older than 50
      years and with negative DRE and PSA < 4 ng/mL, annual evaluations are prudent. In
      patients with a PSA range of 4.0 to 9.9 ng/mL, high-risk groups such as black
      males and those with a positive family history should have TRUS. Males with
      negative DRE in the PSA range of 4.0 to 9.9 ng/mL should have TRUS to evaluate
      prostate volume and PSAD. Biopsy should be considered in those with PSAD > 0.15.
      Men with PSA > 10 ng/mL, even in the presence of an enlarged benign prostate,
      should have multiple directed biopsies under TRUS guidance.

PMID- 1385364
TI  - Differential staining of glycosaminoglycans in the predentine and dentine of rat
      incisor using cuprolinic blue at various magnesium chloride concentrations.
AB  - Rat incisors were fixed with a solution of 0.05% Cuprolinic Blue and 2.5%
      glutaraldehyde in the presence of various concentrations of MgCl2 according to
      the critical electrolyte concentration (CEC) principle. This method allows
      glycosaminoglycans (GAG) to be properly preserved and visualized. Small granules
      were stained by the cationic dye in the predentine in the absence of MgCl2. These
      granules grew in size and became more electron-dense when the concentration of
      the electrolyte was increased. Larger ribbon-like structures and granules were
      seen when 0.3 M MgCl2 was used. In the dentine, tiny dots in close association
      with the surface of the collagen fibres, or their periodic striations, were
      positively stained. A thick electron-dense band located on the dentine side at
      the predentine-dentine junction was seen both with and without 0.05 M MgCl2. With
      higher concentrations of the electrolyte (0.1-0.3 M), this band was reduced to a
      very thin line located at the border of the dentine, along with mineralizing
      collagen fibres. This demonstrated the presence of GAG at the dentine surface and
      therefore indicated that GAG may play a role as nucleator agent.

PMID- 1385365
TI  - AMC-anti-FITC conjugates: novel reagents for amplified immunochemical techniques.
      Immunofluorescent staining of human fibroblasts.
AB  - Fluorescein antibodies were labelled with 7-aminocoumarin (AMC) derivatives, the
      3-acetic acid and the 3-propionic acid N-hydroxysuccinimide esters. The labelled
      antibodies were used in conjunction with fluorescein isothiocyanate (FITC) and
      carboxyfluorescein-conjugated primary and secondary antibodies to develop novel
      immunofluorescent staining procedures. These methods combine the advantages of
      the fluorescence properties of AMC and the ready availability of FITC-labelled
      antisera to provide an amplified fluorescence signal as well as overcoming the
      photobleaching problems in FITC staining. The method is easy to perform and is
      expected to make an important contribution to the improvement of the quality of
      staining achieved with immunofluorescence. Details of the procedure used to stain
      human fibroblasts with antifibronectin antibodies are reported in order to
      illustrate the method.

PMID- 1385366
TI  - Quantitation of adipose conversion and triglycerides by staining intracytoplasmic
      lipids with Oil red O.
AB  - Cultured 3T3-F442A cells differentiate into adipocytes and accumulate lipid
      droplets in the cytoplasm. When fat cells are stained with Oil red O, the degree
      of staining seems to be proportional to the extent of cell differentiation. We
      report here a fast and simple method to quantitate the extent of adipose
      conversion by staining the accumulated lipid with Oil red O and determining the
      amount of extracted dye at 510 nm. The results show that Oil red O specifically
      stains triglycerides and cholesteryl oleate but no other lipids. This technique
      is a valuable tool for processing large numbers of cell cultures or samples in
      which adipose differentiation and/or accumulated triglycerides is to be
      quantitated.

PMID- 1385367
TI  - Immunocytochemical localization of a galanin-like peptidergic system in the brain
      of two urodele and two anuran species (Amphibia).
AB  - Galanin-like immunoreactivity was localized in the brain of Urodela (Ambystoma,
      Pleurodeles) and Anura (Bufo, Xenopus) by immunocytochemistry with anti-porcine
      galanin antiserum. In the four species, immunoreactive perikarya were observed in
      the telencephalon (striatum, amygdala), diencephalon preoptic area mainly along
      the anterodorsal wall of the preoptic recessus, suprachiasmatic nucleus, lateral
      hypothalamus, ventral and dorsal infundibular nuclei, paraventricular organ, and
      rhombencephalon (nucleus of the solitary tract). Galaninergic fibres extended in
      similar regions and in the medial septum, ventral telencephalon, ventral
      hypothalamus, median eminence, and various mesencephalic and rhombencephalic
      regions. Contacts with the cerebrospinal fluid cavity occurred along the preoptic
      recessus (Ambystoma) and the ventral infundibular wall (all species). Fibres were
      scarce in the neurohypophysis. The distal and intermediate lobes of the pituitary
      were virtually devoid of immunoreactivity. The galaninergic system appeared more
      developed in adult amphibia than in young animals, suggesting the stimulating
      influence of sex steroids on the expression of galanin as previously described in
      Anguilla. The extensive distribution of the galanin-like immunoreactive neurons
      in amphibian brains suggests that this peptide may act as a neuromodulatur and/or
      neurotransmitter.

PMID- 1385368
TI  - Preparation and use of the poly-L-lysine-gold probe: a differential marker of
      glomerular anionic sites.
AB  - The conditions required for the production of a polylysine-coated gold (PL-G)
      complex, which shows optimal sensitivity for the demonstration of tissue anionic
      sites, expressed under different conditions of pH have been investigated.
      Problems encountered with this complex have been compared with those found with
      other methods of conjugation of polylysine to colloidal gold. The performance of
      a bovine serum albumin (BSA)-stabilized PL-G complex was examined against other
      PL-G conjugates, including complexes that are commercially available, for the
      detection of heterogeneous glomerular anionic site populations, expressed at pH
      2.5 and pH 7.0.

PMID- 1385369
TI  - A combined ultrastructural approach to the study of nuclear matrix thermal
      stabilization.
AB  - Using mouse erythroleukaemia cells and different ultrastructural techniques, the
      morphology was investigated of the nuclear matrix obtained after incubation at 37
      degrees C of isolated nuclei. If purified nuclei were heated for 45 min at 37
      degrees C, the final matrix exhibited well-recognizable nucleolar remnants, an
      inner network and a peripheral lamina. Without such incubation only the
      peripheral lamina was seen surrounding homogeneous, finely granular material.
      Similar results were obtained with both araldite-embedded and freeze-fractured
      nuclear matrices, although in the latter case the loose granular material was not
      evident. Observations of araldite-embedded, heat-treated nuclei revealed clumping
      of heterochromatin in small, very electron-dense masses with large interchromatin
      spaces. These ultrastructural aspects were even more striking in freeze-fractured
      nuclei. Cytochemical matrix analysis by osmium-amine staining for nucleic acids
      and DNase-gold labelling for DNA localization demonstrated that also matrix
      residual nucleic acids, mostly RNA, are stabilized by heat exposure of isolated
      nuclei. The results demonstrate that the morphology of heat-stabilized nuclear
      matrix is not artefactually affected during the preparation for conventional
      electron microscopy and suggest a possible involvement of nucleic acids in the
      heat-induced stabilization of the nuclear matrix.

PMID- 1385370
TI  - Cryofixed, freeze-dried and paraffin-embedded skin enables successful
      immunohistochemical staining of skin basement membrane antigens.
AB  - Conventional chemical fixation and paraffin-embedding procedures give good
      preservation of morphology, although the antigenicity of many proteins in the
      tissue sample is destroyed. On the other hand, fresh frozen sections can preserve
      the antigenicity, but provide poor morphological preservation. To overcome this
      dilemma, cryofixation and freeze drying were used on human skin tissue, applying
      methodology which has only been used to study lymphoid tissue. First, fresh human
      skin was cryofixed in liquid isopentane (-160 degrees C) cooled by liquid
      nitrogen. The skin was then freeze-dried at -40 degrees C and 10(-2) atmospheric
      pressure for 72 h, followed by embedding in paraffin. Sections 4 microns thick
      taken from this cryofixed, freeze-dried, and paraffin-embedded skin were stained
      with hematoxylin-eosin or used for immunolabeling with antibodies against
      basement membrane antigen, including type IV and type VII collagen, bullous
      pemphigoid antigen, epidermolysis bullosa acquisita antigen, and GB3 antigen. The
      morphological preservation of these sections was as good as that of routine
      formalin-fixed and paraffin-embedded skin sections. The basement membrane was
      clearly immunostained with all antibodies used, and the intensity of the reaction
      was as strong as that seen in frozen sections. Evaluation of antigen distribution
      in conjunction with the detailed skin structure was therefore possible in the
      same sections.

PMID- 1385371
TI  - Quantitative changes of Ricinus communis agglutinin I and Helix pomatia lectin
      binding sites in the acrosome of rat spermatozoa during epididymal transit.
AB  - During passage through the epididymis, spermatozoa undergo a number of changes
      which result in their acquisition of fertility and motility. Some of the changes
      that occur include loss of the cytoplasmic droplet and changes in sperm
      morphology, metabolism and properties of the nucleus and plasma membrane. Changes
      have also been reported in the acrosomic system of mammalian spermatozoa during
      their transit through the epididymis. In the present study, the quantitative
      changes of the glycoconjugate content in the acrosome of rat spermatozoa were
      examined during their passage through the epididymis using lectin-colloidal gold
      cytochemistry. Various regions of the epididymis (initial segment, caput, corpus
      and cauda epididymidis) were fixed by perfusion with 1% or 2% glutaraldehyde
      buffered in sodium cacodylate (0.1 M), dehydrated in ethanol and embedded without
      osmication in Lowicryl K4M. Lectin-colloidal gold labeling was performed on thin
      sections using Ricinus communis agglutinin I (RCA I) or Helix pomatia lectin
      (HPL) to detect D-galactose- and N-acetyl-D-galactosamine-containing
      glycoconjugates, respectively. The labeling density over the acrosome of the
      acrosomic system was evaluated as the number of gold particles per microns 2 of
      profile area using a Zeiss MOP-3 image analyzer. The overall mean labeling
      densities over the acrosome of spermatozoa for each lectin was estimated from 4
      rats and over the four distinct epididymal regions. The mean labeling density of
      the acrosome with RCA I and HPL showed a similar pattern along the epididymis,
      although RCA I revealed approximately twice as many gold particles per epididymal
      region. In either case, there was a significant decrease in the labeling density
      of the acrosome of spermatozoa between the initial segment or caput epididymidis
      and cauda epididymidis (p less than 0.01). A similar decrease was also noted
      between the initial segment and corpus epididymidis (p less than 0.01). No change
      was found between the initial segment and caput epididymidis. Controls showed a
      virtual absence of labeling. These results suggest that in addition to a
      multitude of changes occurring to spermatozoa during epididymal transit, there
      are also significant quantitative changes in the glycoconjugate content within
      the acrosome.

PMID- 1385372
TI  - [Randomized double-blind study of therapy of sudden deafness. Low molecular
      weight dextran + naftidrofuryl vs. low molecular weight dextran + placebo].
AB  - Eighty patients with idiopathic sudden deafness existing no longer than 10 days
      were included in a prospective randomized double-blind study. Patients were
      treated for 10 days with infusions of either 10% low-molecular weight dextran or
      the combination of low-molecular weight dextran with naftidrofuryl. Before
      treatment and after 10 days hearing loss in the affected ear was determined at
      0.5, 1, 2, 3, 4 and 6 kHz. The mean hearing loss was then calculated as the
      average from these values. During monotherapy with low-molecular weight dextran
      the mean hearing loss decreased from 40 to 27 dB compared to 38 to 17 dB when
      naftidrofuryl treatment was added (p < 0.01 between groups). A significant
      benefit of naftidrofuryl on hearing loss was also found at frequencies between
      0.5 and 3 kHz. Furthermore, patients reported better improvement of tinnitus when
      naftidrofuryl was combined with dextran. Two patients receiving dextran alone
      developed side effects: one had an allergic reaction causing withdrawal of
      treatment, which the other case had vertigo, nausea and headache with spontaneous
      recovery. The results of the study showed that treatment with naftidrofuryl in
      addition to hemodilution with low-molecular weight dextran was of therapeutic
      benefit in the therapy of sudden deafness without increasing the rate of side
      effects.

PMID- 1385373
TI  - Mapping of an epitope defined by a human hybridoma antibody (TrD3): a new HLA-B
      supertype associated with a subset of HLA-Bw6.
AB  - The new human-human hybridoma TrD3 secretes a cytotoxic IgM mAb, which reacted
      with 28 of a panel of 56 HLA-typed lymphoblastoid cells. All 28 TrD3+ cells
      expressed the HLA-B supertype Bw6, whereas 10 Bw6+ cells were not recognized by
      the mAb. None of the 17 Bw4 homozygous cells were positive with TrD3. Thus, TrD3
      divided the Bw6+ HLA-B specificities of the cell lines into two subgroups,
      namely, Bw6+TrD3+ and Bw6+TrD3-, and therefore defines a new HLA-B supertype.
      TrD3 reacted strongly with some B8+ cell lines and weakly or not at all with
      others, suggesting a new split of HLA-B8. Compared with cell lines, TrD3 reacted
      more weakly with freshly isolated T cells from blood. The Bw6-specific rat mAb
      SFR8-B6 partially blocked the binding of 125I-labeled TrD3 to a Bw6+ cell line.
      By using cell lines transfected with hybrid genes between HLA-B7 (Bw6+) and HLA
      B27 (Bw6-) as targets in flow cytometry, critical residues for the TrD3 epitope
      could be mapped to the amino acid region 24-62 of the HLA class-I alpha 1 domain.
      Comparison of deduced amino acid sequences of TrD3-positive and -negative cells
      indicated that a tryptophane residue at position 95 destroyed the TrD3 epitope,
      and that one or more of the residues in positions 24, 45, and 46 may be critical,
      suggesting that it is a discontinuous epitope. It is notable that none of these
      residues are located on alpha-helixes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385375
TI  - Kudos to Dr Frymann and colleagues.

PMID- 1385374
TI  - Signal transduction through crosslinking CD7 and IgM-Fc receptors that inhibits T
      cell proliferation.
AB  - We have previously suggested a possible involvement of CD7 and/or the putative
      receptor for IgM-Fc (FcRmu) in the downregulation of T-cell responses to mitogen
      and alloantigen. In this report, we examined the effect of ligand-receptor
      interaction upon T-cell proliferation by using anti-CD7 monoclonal antibodies
      (mAbs) and purified human IgM (HIgM) and showed that crosslinking CD7 and/or
      FcRmu on T cells resulted in significant inhibition of mitogen- and alloantigen
      induced proliferative responses. In most cases, crosslinking of FcRmu alone or
      together with CD7 receptors on peripheral blood lymphocytes (PBLs) resulted in
      more potent suppression of T-cell proliferation than that caused by crosslinking
      CD7 alone. Examination of potential inhibitory mechanisms revealed that
      crosslinking CD7 and FcRmu does not reduce cell viability or the expression of T
      cell markers that are important for T-cell activation or proliferation. However,
      crosslinking CD7 and/or FcRmu of PBLs significantly reduced phytohemagglutinin
      (PHA)-induced IL-2 production and rendered PBLs unable to utilize exogenously
      added human recombinant IL-2 (rIL-2). Further examination of possible signal
      transduction that might be associated with crosslinking CD7 and/or FcRmu
      receptors indicated a marked reduction in the magnitude and duration of
      intracellular calcium (Ca++)i released in response to PHA. These findings suggest
      that crosslinking CD7 and FcRmu inhibits T-cell activation and proliferation by a
      calcium-dependent mechanism that inhibits IL-2 production and/or utilization.

PMID- 1385377
TI  - Connections between the cochlear nuclei in guinea pig.
AB  - This study provides a detailed analysis of the appearances and distributions of
      neurons projecting from one cochlear nucleus to the other. Injections of
      wheatgerm agglutinin conjugated to horseradish peroxidase were made into ventral
      or dorsal cochlear nucleus of the guinea pig. Retrogradely labeled cells in the
      opposite cochlear nucleus were examined and quantified. Three major categories of
      labeled cells were discerned on the basis of their soma shape: elongate, round-to
      oval, and polygonal. All injections resulted in widespread labeling of cells in
      all of these categories, but especially round-to-oval cells, in the opposite
      ventral cochlear nucleus and sparse labeling in the dorsal cochlear nucleus. The
      results suggest that there is a significant cochlear nucleus commissural
      projection involving heterogeneous cell types which could have diverse functions
      in binaural auditory signal processing.

PMID- 1385376
TI  - Developmentally-regulated coexpression of vimentin and cytokeratins in the rat
      inner ear.
AB  - In the present study the expression of vimentin-type intermediate filament
      proteins and cytokeratins was studied immunohistochemically in the rat inner ear
      from 12 days postconception up to 40 days after birth. With the use of a broad
      spectrum monoclonal antibody, cytokeratin expression was found to be present in
      the whole epithelial lining except for the sensory cells, throughout all the
      developmental stages examined. Vimentin was detected in the mesenchymal cells,
      the mesenchyme-derived tissues and the intermediate cells of the stria
      vascularis, confirming their origin from melanocyte precursor cells. In addition,
      the coexpression of vimentin and cytokeratins in the epithelial lining of the
      membranous inner ear was found to be developmentally regulated. During the final
      stages of differentiation, vimentin expression disappeared from the majority of
      the cell types. In the mature cochlea the coexpression of vimentin and
      cytokeratins was still found in the supporting cells of the organ of Corti, in
      the cells of Claudius and in external sulcus cells. As far as we could conclude
      from this study, the sensory cells showed only vimentin expression but not
      cytokeratin expression. A possible relationship between vimentin expression in
      adult epithelial cells of the inner ear and a specialised function of these cells
      is discussed.

PMID- 1385378
TI  - Characterization of marginal and Claudius' cells growing from cochlear explants
      in vitro.
AB  - Tissue specimens of stria vascularis together with spiral ligament were
      transferred from the guinea pig cochlea to tissue culture dishes. To characterize
      and identify cells growing out from the explants, indirect immunofluorescence
      microscopy was used. The expression of the intermediate-sized filaments vimentin
      and cytokeratin 18 in cells on the surface of tissue specimens and in cells
      growing out from the explants after different cultivation periods were compared.
      Basically, three types of cells grew from the explants during several days:
      marginal cells, Claudius' cells and fibroblast-like cells. In primary cultures of
      explants, growth of marginal cells was observed in 25% of the dishes. Their
      proliferative activity, estimated by the use of the BrdUrd-DNA antibody, started
      in the stria vascularis and continued across the attachment of Reissner's
      membrane down to the bottom of the cell culture dish. The newly-formed marginal
      cells expressed cytokeratin 18 in the same way that original marginal cells on
      the tissue specimen do. If the newly-formed marginal cells were in contact with
      fibroblast-like cells or were forming groups (domes) on the bottom, they
      expressed vimentin. In 3% of the dishes growth of Claudius' cells was observed.
      Proliferative activity of these cells was found at the point where the basilar
      membrane was attached to the spiral ligament. New Claudius' cells spread at the
      opposite side of an explant when compared with the location of new marginal
      cells. Original as well as newly-formed Claudius' cells contained cytokeratin 18.
      Fibroblast-like cells were commonly present in cultures and contained only
      vimentin.

PMID- 1385380
TI  - A comparison of the lethal effects in culture of cytosine arabinoside and
      arabinofuranosyl-5-azacytosine acting on the blast cells fo acute myeloblastic
      leukemia.
AB  - Two culture methods are available for the study of the blast cells of acute
      myeloblastic leukemia (AML); first, a minority of blast cells will form colonies
      in methylcellulose cultures in the presence of suitable growth factors. Second,
      clonogenic blast cells will increase in suspension cultures. Both methods can be
      used to assess the sensitivity of blasts to chemotherapeutic drugs, but different
      dose-response curves are obtained with each. Thus cytosine arabinoside (ara-C) is
      more toxic to clonogenic blasts in suspension than in methylcellulose, while for
      5-azacytidine (5-aza) the reverse is seen. Arabinofuranosyl-5-Azacytosine (ara
      AC) combines the chemical features of the two drugs. That is, its sugar moiety
      has the same diastereomeric change in the furanose ring as ara-C and its
      pyrimidine ring has the same substitution of nitrogen for carbon at the 5'
      position as 5-aza. We compared the sensitivity of AML blasts with ara-Ac in
      suspension and in methylcellulose. As a control, the same comparison was made for
      the sensitivities to ara-C. Blast cells were less sensitive to ara-AC than to ara
      C under all conditions; but, ara-AC sensitivity was greater for cells in
      methylcellulose than for cells in suspension. Thus, AML blasts respond to ara-AC
      in culture with a pattern similar to that of 5-aza and opposite to that of ara-C.
      Since ara-C is a more useful drug in the treatment of AML than 5-aza, we
      interpret the culture results as predicting that ara-AC may not be effective in
      AML.

PMID- 1385379
TI  - Effect of porcine somatotropin on number of granulosa cell luteinizing
      hormone/human chorionic gonadotropin receptors, oocyte viability, and
      concentrations of steroids and insulin-like growth factors I and II in follicular
      fluid of lean and obese gilts.
AB  - Prepubertal gilts of obese (n = 24) or lean (n = 24) genetic lines were injected
      (s.c.) daily with 0, 2, or 4 mg of porcine somatotropin (pST) for 6 wk starting
      at 160 d of age to determine whether pST affects follicular function. Blood and
      ovaries were collected at slaughter 24 h after the last injection. Surface
      follicles greater than or equal to 1.0 mm in diameter were counted, and pools of
      follicular fluid (FFL) and granulosa cells were collected from 1.0- to 3.9-mm
      (small) and 4.0- to 6.9-mm (medium) follicles. Oocytes were collected from small
      and medium follicles and evaluated for maturational stage and viability. Porcine
      somatotropin increased (P less than .08) the numbers of small but not the numbers
      of medium follicles per gilt (P greater than .10). Oocyte maturation and
      viability were not affected by pST or genetic line. Porcine somatotropin
      increased (P less than .05) concentrations of insulin-like growth factor I (IGF
      I) in serum and FFL of both obese and lean gilts; IGF-I was lower (P less than
      .01) in lean gilts. Treatment with pST decreased (P less than .05) IGF-II in FFL
      of lean but not in that of obese gilts. Dose of pST and line had no effect on
      concentrations of progesterone in FFL of small or medium follicles or on
      concentrations of estradiol in FFL of small follicles.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1385381
TI  - Scleral fibroblasts of the chick embryo differentiate into chondrocytes in soft
      agar culture.
AB  - Scleral fibroblasts, perichondrial cells of the scleral layer of the 12-day chick
      embryo, always manifest a fibroblastic morphology in monolayer culture. In soft
      agar culture, these cells produce two types of colonies. One type of colony, F
      type, consists of adherent fibroblastic cells, and the other, C-type, is composed
      of scattered round chondrocytic cells. Cells of the C-type colony are surrounded
      by a halo of extracellular matrix, positive with Alcian blue and with an antibody
      to cartilage-specific proteoglycan. When a single fibroblast clone in monolayer,
      derived from a single scleral fibroblast, is subcultured into soft agar, the
      cells give rise to both C-type and F-type colonies. Further, it was found that
      cells constituting F-type colonies eventually separate and become spherical, and
      the F-type colony converts to a C-type colony (C-type conversion). In regard to
      the C-type convertibility, the primary fibroblast clones were divided into four
      categories, early time differentiating, middle-time differentiating, late-time
      differentiating and nondifferentiating. This suggests that the scleral
      perichondrial layer of the 12-day chick embryo is composed of a variety of cells
      with different chondrogenic potentialities maintained in each individual cell.

PMID- 1385382
TI  - Effects of serum acid phosphatase [correction of phosphate] elevation following
      transurethral prostatectomy on long-term mortality.
AB  - Studies of surgery for symptoms of bladder outlet obstruction in men suggest that
      a possible higher long-term mortality occurs in patients having transurethral
      prostatectomy compared with patients having an open prostatectomy. It is the
      purpose of this study to determine if intraoperative factors affect the long-term
      survival of patients having transurethral prostate resection for benign prostate
      hypertrophy. In 158 consecutive patients having transurethral prostatectomy for
      benign adenoma who were followed for eight years, 28 patients died during the
      follow-up period. In comparing those patients who are alive with those patients
      who have died, there was no significant difference at the time of surgery in
      intraoperative irrigant absorption as indicated by changes in serum sodium and
      there was no significant difference in the intraoperative absorption of prostate
      tissue substances as indicated by changes in serum acid phosphatase. The only
      factor in this study associated with long-term survival was age of the patient at
      the time of surgery with older patients having a higher long-term mortality. This
      study suggests that age of the patient rather than intraoperative factors is
      associated with long-term survival following transurethral prostatectomy.

PMID- 1385383
TI  - Management of volunteer and temporary staff in the audio/visual department.

PMID- 1385384
TI  - Physical map of the Listeria monocytogenes chromosome.
AB  - The circular physical map of the pathogenic bacterium Listeria monocytogenes LO28
      (serovar 1/2c) was established by using pulsed-field gel electrophoresis. The L.
      monocytogenes chromosome contains eight NotI fragments of 1,100, 940, 400, 335,
      280, 45, 30, and 20 kb in size and eight Sse8387I fragments of 860, 680, 680,
      370, 335, 130, 70, and 25 kb. Therefore, the total length of the genome is 3,150
      kb. To order the NotI fragments on the chromosome, we used a strategy which can
      be of general use. We first cloned chromosomal HindIII or EcoRI fragments in
      pBR322. DNA extracted from the total libraries was digested by NotI and ligated
      to a NotI-kanamycin resistance cassette obtained by cutting Tn5 with NotI. After
      transformation in Escherichia coli, kanamycin-resistant clones originating from
      NotI-containing EcoRI or HindIII fragments were isolated. The two EcoRI-NotI or
      HindIII-NotI fragments of each recombinant plasmid were isolated and used as
      probes on Southern blot hybridizations to identify and link the corresponding
      NotI fragments. Seven NotI fragments were ordered in this way. The last junction
      was demonstrated by partial digest analysis. All L. monocytogenes genes
      identified so far as well as the six rRNA operons were localized on the NotI map.
      Regions homologous to genes from closely related bacteria were also detected and
      localized. Southern blot analysis of simple Sse8387I digests or double Sse8387I
      NotI digests probed with the various NotI probes allowed us to align the Sse8387I
      fragments and localize the single SfiI site, resulting in the establishment of
      the first genetic and physical map of the L. monocytogenes chromosome.

PMID- 1385385
TI  - How a mutation in the gene encoding sigma 70 suppresses the defective heat shock
      response caused by a mutation in the gene encoding sigma 32.
AB  - In Escherichia coli, transcription of the heat shock genes is regulated by sigma
      32, the alternative sigma factor directing RNA polymerase to heat shock
      promoters. sigma 32, encoded by rpoH (htpR), is normally present in limiting
      amounts in cells. Upon temperature upshift, the amount of sigma 32 transiently
      increases, resulting in the transient increase in transcription of the heat shock
      genes known as the heat shock response. Strains carrying the rpoH165 nonsense
      mutation and supC(Ts), a temperature-sensitive suppressor tRNA, do not exhibit a
      heat shock response. This defect is suppressed by rpoD800, a mutation in the gene
      encoding sigma 70. We have determined the mechanism of suppression. In contrast
      to wild-type strains, the level of sigma 32 and the level of transcription of
      heat shock genes remain relatively constant in an rpoH165 rpoD800 strain after a
      temperature upshift. Instead, the heat shock response in this strain results from
      an approximately fivefold decrease in the cellular transcription carried out by
      the RNA polymerase holoenzyme containing mutant RpoD800 sigma 70 coupled with an
      overall increase in the translational efficiency of all mRNA species.

PMID- 1385386
TI  - Molecular characterization of two Clostridium acetobutylicum ATCC 824 butanol
      dehydrogenase isozyme genes.
AB  - A 4-kb segment of DNA containing two previously cloned butanol dehydrogenase
      (BDH) isozyme genes (D. Petersen, R. Welch, F. Rudolph, and G. Bennett, J.
      Bacteriol. 173:1831-1834, 1991) was sequenced. Two complete open reading frames
      (ORFs) were identified (bdhA and bdhB), along with a third truncated ORF (ORF1).
      The translation products of bdhA and bdhB corresponded to the N-terminal
      sequences of the purified BDH I and BDH II proteins, respectively. The two
      isozymes had a high amino acid identity (73%) and showed homology to a newly
      described class of alcohol dehydrogenases. Northern blots revealed that bdhA and
      bdhB did not form an operon. Primer extension experiments located single
      transcriptional start sites 37 and 58 bp upstream of the start codons of bdhA and
      bdhB, respectively. The -10 and -35 promoter regions for these genes were almost
      identical. bdhA and bdhB were found to be induced or derepressed immediately
      prior to significant butanol production in controlled pH 5.0 batch fermentations.

PMID- 1385387
TI  - Identification of multiple RNA polymerase sigma factor homologs in the
      cyanobacterium Anabaena sp. strain PCC 7120: cloning, expression, and
      inactivation of the sigB and sigC genes.
AB  - The sigA gene of Anabaena sp. strain PCC 7120, encoding the principal RNA
      polymerase sigma factor, and the complement of the rpoD oligonucleotide (K.
      Tanaka, T. Shiina, and H. Takahashi, Science 242:1040-1042, 1988) were used as
      probes to isolate two genes, sigB and sigC, which encode two putative sigma
      factors exhibiting high degrees of similarity to SigA, to HrdA, -B, -C, and -D of
      Streptomyces coelicolor, and to KatF of Escherichia coli. sigB and sigC code for
      polypeptides of 332 and 416 amino acids with predicted molecular weights of
      38,431 and 47,459, respectively. sigB and sigC mRNAs are detectable only under
      nitrogen-limiting conditions. Insertional inactivation of sigB and sigC indicates
      that neither gene alone is essential for nitrogen fixation or heterocyst
      differentiation.

PMID- 1385390
TI  - Aggression, suicidality, and serotonin.
AB  - Studies from several countries, representing diverse cultures, have reported an
      association between violent suicide attempts by patients with unipolar depression
      and personality disorders and low concentrations of the major serotonin
      metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF).
      Related investigations have documented a similar inverse correlation between
      impulsive, externally directed aggressive behavior and CSF 5-HIAA in a subgroup
      of violent offenders. In these individuals, low CSF 5-HIAA concentrations are
      also associated with a predisposition to mild hypoglycemia, a history of early
      onset alcohol and substance abuse, a family history of type II alcoholism, and
      disturbances in diurnal activity rhythm. These data are discussed in the context
      of a proposed model for the pathophysiology of a postulated "low serotonin
      syndrome."

PMID- 1385389
TI  - The luxR gene product of Vibrio harveyi is a transcriptional activator of the lux
      promoter.
AB  - Expression of the lux operon from the marine bacterium Vibrio harveyi is
      dependent on cell density and requires an unlinked regulatory gene, luxR, and
      other cofactors for autoregulation. Escherichia coli transformed with the lux
      operon emits very low levels of light, and this deficiency can be partially
      alleviated by coexpression of luxR in trans. The V. harveyi lux promoter was
      analyzed in vivo by primer extension mapping to examine the function of luxR. RNA
      isolated from E. coli transformed with the Vibrio harveyi lux operon was shown to
      have a start site at 123 bp upstream of the first ATG codon of luxC. This is in
      sharp contrast to the start site found for lux RNA isolated from V. harveyi, at
      26 bp upstream of the luxC initiation codon. However, when E. coli was
      cotransformed with both the lux operon and luxR, the start site of the lux mRNA
      shifted from -123 to -26. Furthermore, expression of the luxR gene caused a 350
      fold increase in lux mRNA levels. The results suggest that LuxR of V. harveyi is
      a transcriptional activator stimulating initiation at the -26 lux promoter.

PMID- 1385391
TI  - Catalytic properties of yeast protein kinase C: difference between the yeast and
      mammalian enzymes.
AB  - With bovine myelin basic protein as a model common substrate, protein kinases C
      (PKC) purified from yeast (Saccharomyces cerevisiae) and mammalian tissue (rat
      brain) were shown to exhibit clearly different catalytic properties. The major
      sites of phosphorylation in bovine myelin basic protein by the yeast PKC were
      identified: Thr-19, Thr-34, and Thr-65. These sites are distinctly different from
      those for the mammalian PKC: Ser-8, Ser-46, Ser-55, Ser-110, Ser-132, Ser-151,
      and Ser-161, which were previously identified [Kishimoto, A., Nishiyama, K.,
      Nakanishi, H., Uratsuji, Y., Nomura, H., Takeyama, Y., & Nishizuka, Y. (1985) J.
      Biol. Chem. 160, 12492-12499]. The results suggest that the yeast and mammalian
      enzymes may play distinct roles in cellular regulation. No evidence is available,
      however, that a yeast-type PKC exists in mammalian tissues. An oligopeptide
      containing the sequence around Thr-19 of bovine myelin basic protein, Lys-Tyr-Leu
      Ala-Ser-Ala-Ser-Thr(19)-Met-Asp-His-Ala, can be used as a substrate for selective
      assaying of the yeast PKC.

PMID- 1385388
TI  - Role of Escherichia coli K-12 rfa genes and the rfp gene of Shigella dysenteriae
      1 in generation of lipopolysaccharide core heterogeneity and attachment of O
      antigen.
AB  - The rfp gene of Shigella dysenteriae 1 and the rfa genes of Escherichia coli K-12
      and Salmonella typhimurium LT2 have been studied to determine their relationship
      to lipopolysaccharide (LPS) core heterogeneity and their role in the attachment
      of O antigen to LPS. It has been inferred from the nucleotide sequence that the
      rfp gene encodes a protein of 41,864 Da which has a structure similar to that of
      RfaG protein. Expression of this gene in E. coli K-12 results in the loss of one
      of the three bands seen in gel analysis of the LPS and in the appearance of a
      new, more slowly migrating band. This is consistent with the hypothesis that Rfp
      is a sugar transferase which modifies a subset of core molecules so that they
      become substrates for attachment of S. dysenteriae O antigen. A shift in gel
      migration of the bands carrying S. dysenteriae O antigen and disappearance of the
      Rfp-modified band in strains producing O antigen suggest that the core may be
      trimmed or modified further before attachment of O antigen. Mutation of rfaL
      results in a loss of the rough LPS band which appears to be modified by Rfp and
      prevents the appearance of the Rfp-modified band. Thus, RfaL protein is involved
      in core modification and is more than just a component of the O-antigen ligase.
      The products of rfaK and rfaQ also appear to be involved in modification of the
      core prior to attachment of O antigen, and the sites of rfaK modification are
      different in E. coli K-12 and S. typhimurium. In contrast, mutations in rfaS and
      rfaZ result in changes in the LPS core but do not affect the attachment of O
      antigen. We propose that these genes are involved in an alternative pathway for
      the synthesis of rough LPS species which are similar to lipooligosaccharides of
      other species and which are not substrates for O-antigen attachment. All of these
      studies indicate that the apparent heterogeneity of E. coli K-12 LPS observed on
      gels is not an artifact but instead a reflection of functional differences among
      LPS species.

PMID- 1385392
TI  - Inhibitory effects of triphosphate derivatives of oxetanocin G and related
      compounds on eukaryotic and viral DNA polymerases and human immunodeficiency
      virus reverse transcriptase.
AB  - In order to clarify the biological activities of (-)-oxetanocin G, and (-)
      oxetanocin A and its carbocyclic analogue, (-)-carboxetanocin G, the inhibitory
      effects of triphosphate derivatives of these compounds (OXT-GTP, OXT-ATP, and C
      OXT-GTP) on eukaryotic and viral DNA polymerases were examined. DNA polymerase
      alpha purified from calf thymus was weakly inhibited by OXT-GTP and OXT-ATP but
      strongly by C-OXT-GTP, the Ki value being 0.22 microM. On the other hand, rat DNA
      polymerase beta was not affected by these analogues. DNA polymerase gamma
      purified from bovine testes was very weakly inhibited by OXT-GTP and OXT-ATP, but
      not by C-OXT-GTP. DNA polymerase from herpes simplex virus type-II (HSV-II) was
      strongly inhibited by all three analogues, the Ki values ranging from 0.5 to 1.0
      microM. Human immunodeficiency virus-encoded reverse transcriptase (HIV RT) was
      also strongly inhibited by these three analogues, the Ki value of C-OXT-GTP being
      slightly smaller than that of OXT-GTP or OXT-ATP. Analysis of products
      synthesized on singly primed M13 single-stranded DNA by DNA polymerase alpha, HSV
      II DNA polymerase or HIV RT in the presence of the analogues revealed that OXT
      GTP and C-OXT-GTP were incorporated into DNA and caused chain termination mainly
      at sites one or two nucleotides beyond the cytosine bases on the template.

PMID- 1385393
TI  - The reversible and irreversible autophosphorylations of insulin receptor kinase.
AB  - When the catalytically active, tyrosyl-phosphorylated form of insulin receptor
      was isolated from human placenta and treated with ADP, only partial
      dephosphorylation was observed. This observation suggests the existence of two
      distinct classes of phosphotyrosyl residues of the phosphorylated insulin
      receptor: one in which the phosphoryl groups undergo reversible transfer to ADP
      and one in which they do not. There were 8.8 +/- 2.2 phosphorylation sites per
      tetrameric insulin receptor, of which 2.4 +/- 0.5 were irreversible (mean +/-
      S.D., n = 6). The reversible sites were determined to be equivalent and
      noninteracting and to have an equilibrium constant for the transfer of a
      phosphoryl group from ATP to a site of reversible phosphorylation of 8.7.
      Surprisingly, both phosphorylation and dephosphorylation at the reversible sites
      were relatively insensitive to the presence of insulin. Since only minimal
      autophosphorylation of insulin receptor was detected in the absence of insulin,
      the results suggest that the incorporation of phosphate into the two to three
      irreversible phosphorylation sites is insulin dependent. Phosphorylation of the
      irreversible phosphorylation sites then renders the insulin receptor relatively
      insensitive to the continued presence of insulin and facilitates rapid reversible
      phosphorylation of a second group of tyrosyl residues. The dependence of the
      degree of phosphorylation of insulin receptor on the ATP:ADP ratio may provide a
      mechanism for modulating the cellular response to insulin.

PMID- 1385394
TI  - Catalytic properties of the cloned amylase from Bacillus licheniformis.
AB  - A gene encoding a new amylolytic enzyme of Bacillus licheniformis (BLMA) has been
      cloned, and we characterized the enzyme expressed in Escherichia coli. The
      genomic DNA of B. licheniformis was double-digested with EcoRI and BamHI and
      ligated the pBR322. The transformed E. coli was selected by its amylolytic
      activity, which carries the recombinant plasmid pIJ322 containing a 3.5-kilobase
      fragment of B. licheniformis DNA. The purified enzyme encoded by pIJ322 was
      capable of hydrolyzing pullulan and cyclodextrin as well as starch. It was active
      over a pH range of 6-8 and its optimum temperature was 50 degrees C. The
      molecular weight of the enzyme was 64,000, and the isoelectric point was 5.4. It
      degraded soluble starch by cleaving maltose units preferentially but did not
      attack alpha-1,6-linkage. The enzyme also hydrolyzed pullulan to panose units
      exclusively. In the presence of glucose, however, it transferred the panosyl
      moiety to glucose with the formation of alpha-1,6-linkage. The specificity of
      transferring activity is evident from the result of the maltosyl-transferring
      reaction which produces isopanose from maltotriose and glucose. The molecular
      structure of the enzyme deduced from the nucleotide sequence of the clone
      maintains limited similarity in the conserved regions to the other amylolytic
      enzymes.

PMID- 1385395
TI  - Glycophorin A facilitates the expression of human band 3-mediated anion transport
      in Xenopus oocytes.
AB  - The effects of human red cell glycophorin A (GPA) on the expression of the human
      erythrocyte anion transporter (band 3, AE1) has been examined in Xenopus oocytes.
      The coexpression of GPA with band 3 increased stilbene disulfonate-sensitive
      chloride transport into the oocytes. The effect of GPA was particularly
      noticeable at low band 3 concentrations and less marked at high band 3 cRNA
      concentrations. The enhancement of chloride transport was specific to GPA and was
      not observed when either glycophorin B or glycophorin C was coexpressed with band
      3. Immunoprecipitations of whole oocyte homogenates showed the amount of band 3
      synthesized was not affected by GPA at subsaturating cRNA concentrations. More
      band 3 was detected at the oocyte surface by immunoprecipitation when GPA was
      also expressed. Chymotrypsin treatment of intact oocytes was also used to assess
      surface band 3 and greater cleavage of band 3 by chymotrypsin was observed when
      GPA was present. Band 3 synthesis and assembly into canine pancreatic microsomes
      in the reticulocyte cell-free translation system was not altered by cotranslation
      of GPA. We suggest that GPA facilitates the translocation of band 3 to the plasma
      membrane at some point during band 3 biosynthesis in Xenopus oocytes. However,
      GPA is not essential for the expression of band 3 in red cells, since GPA
      deficient individuals have apparently normal levels of band 3. Other GPA
      independent mechanisms must also allow translocation of band 3 to the surface
      membrane in erythroid cells and oocytes. GPA may affect the rate of accumulation
      of band 3 at the cell surface, rather than the final level in the plasma
      membrane.

PMID- 1385396
TI  - Insulin stimulation of phosphatidylinositol 3-kinase activity and association
      with insulin receptor substrate 1 in liver and muscle of the intact rat.
AB  - Growth factors stimulate the enzyme phosphatidylinositol (PI) 3-kinase in cells
      in culture. Insulin rapidly stimulates tyrosine phosphorylation of its endogenous
      substrate, insulin receptor substrate 1 (IRS-1), and in vitro IRS-1 associates
      with PI 3-kinase, thus activating the enzyme. We have examined whether insulin is
      capable of stimulating the PI 3-kinase pathway in two physiological target
      tissues for the actions of insulin in vivo, liver and skeletal muscle. After
      intraportal injection of insulin into anesthetized rats, there was a 2-fold
      stimulation of total hepatic PI 3-kinase activity in liver and muscle extracts
      and a 10- to 20-fold increase in PI 3-kinase activity immunoprecipitated with
      anti-IRS-1 antibodies. Stimulation of PI 3-kinase was accompanied by an
      association between this enzyme and IRS-1 as detected by immunoprecipitation of
      liver and muscle extracts with anti-IRS-1 antibodies and Western blotting with
      antibodies to the 85-kDa subunit of PI 3-kinase. Immunoprecipitation with anti
      p85 antibodies and phosphotyrosine immunoblotting revealed no tyrosine
      phosphorylation of PI 3-kinase, but demonstrated co-precipitation of tyrosine
      phosphorylated IRS-1, as well as another phosphotyrosine protein of approximately
      135-140 kDa. Thus, IRS-1 phosphorylation plays a significant role in the
      activation of PI 3-kinase in vivo by insulin.

PMID- 1385397
TI  - Identification of a glycine-rich sequence as an NAD(P)H-binding site and tyrosine
      128 as a dicumarol-binding site in rat liver NAD(P)H:quinone oxidoreductase by
      site-directed mutagenesis.
AB  - Site-directed mutagenesis was utilized to identify binding sites for NAD(P)H and
      dicumarol in rat liver NAD(P)H:quinone oxidoreductase (NQOR, EC 1.6.99.2). The
      mutant cDNA clones were generated by a procedure based on the polymerase chain
      reaction and were expressed in Escherichia coli. The mutant enzymes were purified
      to apparent homogeneity as judged by SDS-polyacrylamide gel electrophoresis and
      were found to contain 2 FADs/enzyme molecule identical with that of the wild-type
      NQOR. Purified mutant enzymes Y128D, G150F, G150V, S151F, and Y155D showed
      dramatic decreases in activities in the reduction of dichlorophenolindophenol in
      comparison with the activities of the wild-type enzyme, whereas the activities of
      F124L, T127V, T127E, Y128V, Y128F, S151A, and Y155V were similar to those of
      NQOR. Enzyme kinetic analysis revealed that the Km values of T127E, Y128D, G150F,
      G150V, S151F, and Y155D were, respectively, 4-, 2-, 13-, 5-, 26-, and 19-fold
      higher than the Km of NQOR for NADPH, and were, respectively, 2-, 3-, 7-, 3-, 20
      , and 11-fold higher than that of NQOR for NADH. The kcat values of Y128D, G150F,
      and G150V were also much lower than those of NQOR, but the kcat values of other
      mutants were similar to those of the wild-type enzyme. The Km values of the
      mutants for dichlorophenolindophenol were the same or slightly higher than that
      of NQOR. The apparent inhibition constants (Ki) for dicumarol on Y128V and F124L
      were elevated 12 and 8 times, respectively. Similar, but smaller, changes on Ki
      for 4-hydroxycoumarin were also observed. This study demonstrated that residues
      Gly150, Ser151, and Tyr155 in the glycine-rich region of NQOR are essential for
      NADPH and NADH binding and Tyr128 is important for dicumarol binding. Based on
      the results of the study, it is proposed that the glycine-rich region of the
      enzyme, along with other residues around the region, forms a beta sheet-turn
      alpha helix structure important for the binding of the pyrophosphate group of
      NADPH and NADH.

PMID- 1385398
TI  - A T-cell enhancer cooperates with NF-kappa B to yield cytokine induction of E
      selectin gene transcription in endothelial cells.
AB  - ELAM1 (endothelial leukocyte adhesion molecule 1, also known as E-selectin) is a
      highly tissue-specific adhesion molecule that is transiently and exclusively
      expressed on cytokine-induced endothelial cells. We have identified two proximal
      ELAM1 promoter elements and their DNA-binding factors that are, in addition to NF
      kappa B, essential for ELAM1 transcription. Mutation of either element in
      promoter constructs carrying the first 383 nucleotides of the ELAM1 promoter
      markedly diminshed the expression of a fused chloramphenicol acetyltransferase
      reporter gene. Although multimers of either element failed to display enhancer
      activity on its own, fusion of the most upstream of these to the NF-kappa B
      element had a strong stimulatory effect. This site, ACATCAT, is recognized by a
      factor we have called NF-ELAM1. The site corresponds to NF-ELAM1's preferential
      binding sequence (A/T)CA(G/T)CA(G/T) as determined in a target definition assay.
      This element is identical to the T-cell delta A enhancer found in the T-cell
      receptor-alpha, -beta, and CD3 delta genes. Our results suggest that the delta
      A/NF-ELAM1 element can function as a modulator of NF-kappa B in endothelial cells
      both as well as a T-cell enhancer.

PMID- 1385399
TI  - N-glycosylation is required for human CD2 immunoadhesion functions.
AB  - The T-lymphocyte glycoprotein receptor, CD2, mediates cell-cell adhesion by
      binding to the surface molecule CD58 (LFA-3) on many cell types including antigen
      presenting cells. Two domains comprise the CD2 extracellular segment, with all
      adhesion functions localized to the amino-terminal domain that contains a single
      N-glycosylation site at Asn65. We have defined an important role for the N-linked
      glycans attached to Asn65 of this domain in mediating CD2-CD58 interactions and
      also characterize its N-glycotype structure. Analysis of deglycosylated soluble
      recombinant CD2 as well as a mutant transmembrane CD2 molecule containing a
      single Asn65-Gln65 substitution demonstrates that neither deglycosylated CD2 nor
      the mutant CD2 transmembrane receptor binds CD58 or monoclonal antibodies
      directed at native CD2 adhesion domain epitopes. Electrospray ionization-mass
      spectrometry demonstrates that high mannose oligosaccharides ((Man)nGlcNAc2, n =
      5-9) are the only N-glycotypes occupying Asn65 when soluble CD2 is expressed in
      Chinese hamster ovary cells. Based on a model of human CD2 secondary structure,
      we propose that N-glycosylation is required for stabilizing domain 1 in the human
      receptor. Thus, N-glycosylation is essential for human CD2 adhesion functions.

PMID- 1385400
TI  - Human osteoblast-derived insulin-like growth factor (IGF) binding protein-5
      stimulates osteoblast mitogenesis and potentiates IGF action.
AB  - Insulin-like growth factor (IGF)-binding proteins (IGFBPs) either inhibit or
      enhance IGF-stimulated cellular effects. While inhibition occurs by sequestration
      of IGF from cell-surface receptors, the exact mechanism of IGF-enhancement
      remains undefined. Human osteoblast-like bone cells in culture secrete several
      IGF-binding proteins, one of which we have previously identified as IGFBP-5. In
      this study we purified a 23-kDa IGFBP-5 from cultures of human osteoblast-like
      cells using ligand affinity chromatography and reversed-phase high performance
      liquid chromatography and tested its bioactivity in serum-free cultures of normal
      mouse osteoblast-like cells. Binding studies with radioiodinated IGF showed
      similar and relatively low affinities for IGF-I and IGF-II consistent with a
      carboxyl truncated IGF-binding protein. Mitogenic assays demonstrated that the
      binding protein, when coincubated with IGF-I or -II, enhanced mitogenesis. This
      enhancement was unique from other binding proteins in not requiring a
      preincubation period or serum co-factors. Furthermore, the osteoblast-derived
      IGFBP-5 stimulated mitogenesis in the absence of exogenous or endogenous IGF.
      Using radioiodinated IGFBP-5 we found that the binding protein could associate
      with the osteoblast surface, an effect which did not require IGF nor an
      interaction with IGF receptors. We suggest that osteoblast-derived IGFBP-5 may
      stimulate osteoblast mitogenesis in at least two ways, by association with IGF
      and by a second pathway that is independent of IGF receptor activation.

PMID- 1385401
TI  - Insulin treatment stimulates the tyrosine phosphorylation of the alpha-type 85
      kDa subunit of phosphatidylinositol 3-kinase in vivo.
AB  - After adding insulin to cells overexpressing the insulin receptor, the activity
      of phosphatidylinositol (PI) 3-kinase in the anti-phosphotyrosine
      immunoprecipitates was rapidly and greatly increased. This enzyme may therefore
      be a substrate for the insulin receptor tyrosine kinase and may be one of the
      mediators of insulin signal transduction. However, it is unclear whether or not
      activated tyrosine kinase of the insulin receptor directly phosphorylates PI 3
      kinase at tyrosine residue(s) and whether insulin stimulates the specific
      activity of PI 3-kinase. We reported previously that the 85-kDa subunit of
      purified PI 3-kinase was phosphorylated at tyrosine residue(s) by the insulin
      receptor in vitro. To examine the tyrosine phosphorylation of PI 3-kinase and
      change of its activity by insulin treatment in vivo, we used a specific antibody
      to the 85-kDa subunit of PI 3-kinase. The activity of PI 3-kinase in
      immunoprecipitates with the antibody against the p85 subunit of PI 3-kinase was
      increased about 3-fold by insulin treatment of cells overexpressing insulin
      receptors. Insulin treatment also stimulated the tyrosine, serine, and threonine
      phosphorylation of the alpha-type 85-kDa subunit of PI 3-kinase in vivo.
      Phosphatase treatment of the immunoprecipitates abolished the increase in PI 3
      kinase activity. The phosphorylation(s) of the kinase itself, tyrosine
      phosphorylation(s) of associated protein(s), or the complex formation of the
      phosphorylated PI 3-kinase with associated proteins may increase the activity of
      PI 3-kinase.

PMID- 1385402
TI  - N-linked oligosaccharides of murine major histocompatibility complex class II
      molecule. Role in antigenic peptide binding, T cell recognition, and clonal
      nonresponsiveness.
AB  - To evaluate the functional role of the N-linked oligosaccharides of major
      histocompatibility complex (MHC) class II molecules, affinity-purified murine IAs
      class II molecules were deglycosylated in the presence of asparagine amidase
      enzyme. The deglycosylated IAs molecules were characterized by 12% SDS
      polyacrylamide gel analysis under reduced and native conditions and the complete
      enzymatic removal of all three N-linked sugar components from the alpha/beta
      heterodimer was confirmed by lectin-link Western blot analysis. Like the native
      IAs molecules, the deglycosylated IAs molecules were fully capable of binding an
      antigenic peptide from myelin basic protein MBP(89-101). The kinetics of
      dissociation of preformed complexes of IAs.MBP(89-101) and deglycosylated
      IAs.MBP(89-101) were compared at 4 and at 37 degrees C. Both complexes were
      equally stable at 4 degrees C; however, at 37 degrees C the deglycosylated
      IAs.MBP(89-101) complexes showed an increased rate of dissociation as compared
      with the native IAs.MBP(89-101) complexes. When tested for their ability to
      recognize the T cell receptor on T cells, both complexes bound to cloned HS-1 T
      cells that recognize and respond to IAs.MBP(89-101). Finally, the complexes of
      deglycosylated IAs.MBP(89-101) were tested for the induction of in vitro
      nonresponsiveness and compared with native IAs.MBP(89-101) complexes. Both
      complexes were capable of inducing 95-100% nonresponsiveness in a proliferation
      assay. These results suggest that the N-linked oligosaccharide of MHC class II
      molecules may not be essential for either antigenic peptide binding or T cell
      recognition. In addition results obtained here provide evidence that the
      carbohydrate moities of MHC class II molecules may not be involved in induction
      of T cell clonal anergy.

PMID- 1385404
TI  - Cloning and expression of a cDNA encoding human endothelium-derived relating
      factor/nitric oxide synthase.

PMID- 1385403
TI  - Expression and function of IRS-1 in insulin signal transmission.
AB  - IRS-1 is a major insulin receptor substrate which may play an important role in
      insulin signal transmission. The mRNA for IRS-1 in rat cells and tissues is about
      9.5 kilobases (kb). Rat liver IRS-1 was stably expressed in Chinese hamster ovary
      (CHO) cells (CHO/IRS-1). Although its calculated molecular mass is 131 kDa, IRS-1
      from quiescent cells migrated between 165 and 170 kDa during sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. IRS-1 was phosphorylated strongly on
      serine residues and weakly on threonine residues before insulin stimulation.
      Insulin immediately stimulated tyrosine phosphorylation of IRS-1, and after 10-30
      min with insulin its apparent molecular mass increased to 175-180 kDa. Expression
      of the human insulin receptor and rat IRS-1 together in CHO/IR/IRS-1 cells
      increased the basal serine phosphorylation of IRS-1 and strongly increased
      tyrosine phosphorylation during insulin stimulation. Purified insulin receptors
      directly phosphorylated baculovirus-produced IRS-1 exclusively on tyrosine
      residues. By immunofluorescence, IRS-1 was absent from the nucleus, but otherwise
      distributed uniformly before and after insulin stimulation. Some IRS-1 associated
      with the insulin receptor during insulin stimulation. In addition, a
      phosphatidylinositol 3'-kinase associated with IRS-1 during insulin stimulation,
      and this association was more sensitive to insulin in CHO cells overexpressing
      the insulin receptor (CHO/IR cells), more responsive to insulin to CHO/IRS-1
      cells, and both sensitive and responsive in CHO/IR/IRS-1 cells. Similarly,
      insulin-stimulated DNA synthesis was more sensitive to insulin in CHO/IR cells,
      and more responsive in CHO/IRS-1 cells; however, insulin-stimulated DNA synthesis
      was sensitive but poorly responsive to insulin in CHO/IR/IRS-1 cells. Together,
      these results suggest that IRS-1 is a direct physiologic substrate of the insulin
      receptor and may play an important role in insulin signal transmission.

PMID- 1385405
TI  - A novel glucuronyltransferase in nervous system presumably associated with the
      biosynthesis of HNK-1 carbohydrate epitope on glycoproteins.
AB  - Recently, embryonic chicken brain extract was shown to contain a
      glucuronyltransferase, which transfers glucuronic acid from UDP-glucuronic acid
      to glycolipid acceptors (neolactotetraosyl ceramide). The enzyme was also
      suggested to transfer glucuronic acid to glycoprotein acceptors
      (asialoorosomucoid) (Das, K. K., Basu, M., Basu, S., Chou, D. K. H., and
      Jungalwala, F. B. (1991) J. Biol. Chem. 266, 5238-5243). In this study, the
      glucuronyltransferase activity in rat brain extract was separated into two groups
      by UDP-glucuronic acid-Sepharose CL-6B column chromatography. The enzyme
      recovered predominantly in the effluent fraction (GlcAT-L) catalyzed the transfer
      of glucuronic acid to glycolipid acceptors but not to glycoprotein acceptors,
      whereas the enzyme recovered in the eluate fraction (GlcAT-P) transferred
      glucuronic acid most predominantly to glycoprotein acceptors and very little to
      glycolipid acceptors. GlcAT-P was able to transfer glucuronic acid to
      oligosaccharide chains on asialoorosomucoid. The enzyme recognized a terminal
      lactosamine structure, Gal beta 1-4GlcNAc, on glycoproteins. It was localized in
      the nervous system and was hardly detectable in other tissues, including the
      thymus, spleen, lung, kidney, and liver. Although GlcAT-L and GlcAT-P shared some
      properties in common such as tissue distributions and developmental changes, they
      exhibited marked differences in their phospholipid dependence and in their pH
      profiles, apart from their respective acceptor preference to glycolipids and
      glycoproteins. The acceptor specificity and tissue distribution suggest that a
      novel glucuronyltransferase, GlcAT-P, is involved in the biosynthesis of the
      sulfoglucuronylgalactose structure in the HNK-1 carbohydrate epitope that is
      expressed on glycoproteins.

PMID- 1385406
TI  - Expression of a cDNA for a neuronal calcium channel alpha 1 subunit enhances
      secretion from adrenal chromaffin cells.
AB  - A synthetic oligonucleotide was used to isolate mouse brain cDNA clones coding
      for a brain isoform of the alpha 1 subunit of the voltage-sensitive Ca2+ channel.
      Twenty-six independent cDNA clones were isolated and sequenced. All the cDNA
      clones reported here showed high homology to the rat brain class C cDNA sequence
      (Snutch, T. P., Tomlinson, W. J., Leonard, J. P., and Gilbert, M. M. (1991)
      Neuron 7, 45-57). Comparison of the individual mouse brain class C (mbC) cDNA
      sequences indicated the presence of four regions within the alpha 1 subunit
      coding sequence where alternative splicing can take place in mouse brain and
      raise the possibility that combinatorial arrangement of these splice variants
      could give rise to a heterogenous class of mbC transcripts. Northern blot
      analysis demonstrated that mbC mRNA sequences could be detected in highest
      abundance in mouse heart, at lower levels in mouse brain and spinal cord, and not
      at all in liver or skeletal muscle. An expression vector for one isoform of the
      mbC alpha 1 subunit cDNA was constructed using the human cytomegalovirus promoter
      to direct expression, and this expression vector was used in a novel transfection
      assay of primary cultures of bovine adrenal chromaffin cells. Transfection of the
      mbC alpha 1 subunit expression vector increased the secretion of human growth
      hormone derived from a cotransfected human growth hormone expression vector after
      stimulation with elevated K+ or the dihydropyridine agonist, Bay K8644. These
      experiments suggest that this isoform of the mbC alpha 1 subunit is functional in
      the transfected chromaffin cells and that the number of Ca2+ channels is a
      limiting component in the secretion from chromaffin cells in culture.

PMID- 1385407
TI  - Identification of residues in GTPase-activating protein Src homology 2 domains
      that control binding to tyrosine phosphorylated growth factor receptors and p62.
AB  - Ras GTPase-activating protein (GAP) contains two Src homology 2 (SH2) domains
      which are implicated in binding to tyrosine-phosphorylated sites in specific
      activated growth factor receptors and to a cytoplasmic tyrosine-phosphorylated
      protein, p62. We have used site-directed mutagenesis of the two GAP SH2 domains
      (SH2-N and SH2-C) to identify residues involved in receptor and p62 binding. A
      bacterial fusion protein containing the precise SH2-N domain, as defined by
      sequence homology, associated with both the activated beta platelet-derived
      growth factor receptor and epidermal growth factor receptor, and p62 in vitro.
      However, short deletions at either the N or C termini of the SH2-N domain
      abolished binding, suggesting that the entire SH2 sequence is required for
      formation of an active domain. Conservative substitutions of 2 highly conserved
      basic residues in the SH2-N domain, an arginine and a histidine, resulted in
      complete loss of receptor and p62 binding, whereas other basic residues, and
      residues at variable SH2 sites, were more tolerant of substitution. The conserved
      arginine and histidine therefore appear critical for association with
      phosphotyrosine-containing proteins, possibly through an interaction with
      phosphotyrosine. The GAP SH2-C domain, unlike SH2-N, does not bind efficiently to
      activated receptors or p62 in vitro. The SH2-C domain lacks 3 residues which are
      otherwise well conserved, and contribute to high affinity SH2-N binding.
      Replacement of 1 of these residues, a cysteine, with the consensus glycine,
      conferred SH2-C binding activity toward tyrosine-phosphorylated p62 and epidermal
      growth factor receptor. Loss-of-function and gain-of-function mutations in the
      GAP SH2 domains can therefore be used to identify residues that are critical for
      receptor and p62 binding.

PMID- 1385408
TI  - Purification, cloning, and molecular characterization of a high molecular weight
      hemorrhagic metalloprotease, jararhagin, from Bothrops jararaca venom. Insights
      into the disintegrin gene family.
AB  - A large hemorrhagin, jararhagin, has been cloned from a Bothrops jararaca venom
      gland cDNA expression library. The cDNA sequence predicts a 421-amino acid
      residue molecule with strong amino acid sequence homology and similar domain
      structure to HR1B, a high molecular weight hemorrhagic metalloprotease isolated
      from Trimeresurus flavoviridis (Habu) venom. Like HR1B, jararhagin contains
      enzyme, disintegrin, and cysteine-rich carboxyl-terminal regions. In the
      disintegrin region, the Arg-Gly-Asp sequence is replaced by Glu-Cys-Asp, as found
      in non-Arg-Gly-Asp disintegrin regions of HR1B and a guinea pig sperm fusion
      protein PH-30 beta. The cDNA sequence of jararhagin predicts a precursor protein
      (proprotein) with striking similarity to cryptic regions in precursors of the
      disintegrin peptides trigramin and rhodostomin. Comparison of jararhagin with
      disintegrin precursors highlights the modular arrangement of proprotein,
      metalloprotease, and disintegrin domains in the metalloprotease/disintegrin
      family and provides an insight into their biosynthesis and evolution.

PMID- 1385410
TI  - Uptake, intracellular transport, and degradation of polyethylene glycol-modified
      asialofetuin in hepatocytes.
AB  - Polyethylene glycol (PEG) is attached to proteins in order to increase their half
      life in the circulation and reduce their immunogenicity in vivo. For many
      applications involving "targeting" molecules, it is important to know how PEG
      modification of the molecule affects its interaction with a receptor and the
      subsequent internalization, intracellular transport, and lysosomal degradation.
      As a model system, we used asialofetuin, which binds to the galactose receptor of
      hepatocytes, because removal of sialic acid exposes galactose residues. We
      modified asialofetuin by attaching various amounts of PEG of molecular weight
      1900 or 5000. The preparations were labeled with 125I so that endocytosis and
      degradation could be followed in suspended hepatocytes. Depending on the number
      of PEG molecules attached, receptor-mediated uptake was affected to varying
      degrees. If two-thirds of the exposed amino groups of the asialofetuin molecule
      were modified, the rate of uptake decreased to less than one-fourth of controls;
      degradation of endocytosed molecules was 12% of controls. The reduction in
      endocytic uptake was due to a reduced rate of formation of the receptor-ligand
      complex. Subcellular frationation in density gradients showed that PEG-modified
      asialofetuin is transported intracellularly and degraded in the same manner as
      the native protein, but the rate of proteolysis is reduced. This observation
      explains the paradoxical result of experiments with injection of modified
      asialofetuin into rats in vivo: even though the clearance of one preparation of
      PEG-asialofetuin was much slower than that of the native protein, accumulation of
      radioactivity in the liver from the modified protein was twice as high. The
      hepatocytes accounted for 85% of the hepatic accumulation of either PEG-modified
      or native asialofetuin in vivo.

PMID- 1385409
TI  - Skeletal muscle and brain isoforms of a beta-subunit of human voltage-dependent
      calcium channels are encoded by a single gene.
AB  - Clones of the beta 1-subunit of the voltage-dependent calcium channel (VDCC) from
      human skeletal muscle and hippocampus cDNA libraries, and from human genomic
      libraries, were isolated using a human skeletal muscle beta 1 cDNA probe
      generated by polymerase chain reaction. The skeletal muscle beta 1 cDNA (beta 1M)
      encodes a protein of 523 amino acids that is 97% identical to the rabbit skeletal
      muscle beta-subunit. Two different cDNAs, beta 1B1 and beta 1B2, were obtained
      from the human hippocampus library. The beta 1B1 transcript encodes a protein of
      478 amino acids that is identical to the skeletal muscle beta-subunit (beta 1M),
      except for an internal region of 52 amino acids. The beta 1B2 transcript encodes
      a protein of 596 amino acids. The beta 1B2 polypeptide is identical to the beta
      1B1 polypeptide at amino acids 1-444; however, it has a unique 152 amino acid
      carboxyl terminus. Like beta 1B1, it differs from beta 1M at the internal 52
      amino acids. Analysis of the beta 1 gene structure demonstrates that these three
      cDNAs represent transcripts encoded by a single beta 1 gene. Transcripts from the
      beta 1 gene were detected in RNA from skeletal muscle, heart, spleen, and brain,
      but not in RNA from liver, stomach, or kidney.

PMID- 1385411
TI  - Early loss of the tyrosyl radical in ribonucleotide reductase of adenocarcinoma
      cells producing nitric oxide.
AB  - Nitric oxide (NO) has been previously shown to inhibit crude preparations of
      ribonucleotide reductase, a key enzyme in DNA synthesis, and to destroy the
      essential tyrosyl free radical in pure recombinant R2 subunit of the enzyme. In
      R2-overexpressing TA3 cells, a decrease in the tyrosyl radical was observed by
      whole-cell EPR spectroscopy, as soon as 4 h after NO synthase induction by
      immunological stimuli. Complete loss of the tyrosyl EPR signal occurred after 7 h
      in cells cultured at a high density. Disappearance of the tyrosyl radical was
      prevented by N omega-nitro-L-arginine, a specific inhibitor of NO synthesis, and
      by oxyhemoglobin, which reacts rapidly with NO. It was reproduced by S
      nitrosoglutathione, a NO-releasing molecule. Stable end products of NO synthase
      metabolism did not affect the radical. Immunoblot analysis of the R2 subunit
      indicated that expression of the protein was not influenced by NO synthase
      activity. These results establish that NO, or a labile product of NO synthase,
      induces the disappearance of the R2-centered tyrosyl radical. Since the radical
      is necessary for ribonucleotide reductase activity, its destruction by NO would
      contribute markedly to the antiproliferative action exerted by macrophage-type NO
      synthase.

PMID- 1385412
TI  - Heparin-binding properties of vitronectin are linked to complex formation as
      illustrated by in vitro polymerization and binding to the terminal complement
      complex.
AB  - Vitronectin (VN, complement S-protein) is a multifunctional protein which
      participates in cell adhesion, coagulation, fibrinolysis, and protection against
      complement lysis. VN is incorporated into several complexes, such as the terminal
      complement complex and thrombin-antithrombin III, and is bound to plasminogen
      activator inhibitor 1. The present study showed that purified VN spontaneously
      forms polymers of approximately 1000 kDa with a Stokes radius of 10 nm. The
      polymers are to a varying extent stabilized by disulfide bonds, but are quite
      stable even after reduction and alkylation, indicating the importance of
      noncovalent bonds. Plasma VN circulates mainly as a 65/75-kDa monomer containing
      a cryptic heparin-binding site which is exposed upon a conformational change
      induced by different stimuli, such as coagulation, heating, adsorption to
      surfaces, or exposure to acids, urea, or other denaturating agents. In the
      present study, VN was demonstrated to expose its heparin-binding site and its
      conformationally dependent 8E6 epitope when incorporated into the terminal
      complement complex. We suggest that exposure of the heparin-binding site and a
      putative hydrophobic binding site of VN are linked events dependent upon the same
      conformational change. In vivo, complex formation probably induces the heparin
      binding site. Such a link might also explain why purified heparin-binding VN
      spontaneously forms polymers. The heparin-binding site may be involved in the
      elimination of multimolecular complexes containing VN.

PMID- 1385413
TI  - Incorporation of type I collagen molecules that contain a mutant alpha 2(I) chain
      (Gly580-->Asp) into bone matrix in a lethal case of osteogenesis imperfecta.
AB  - To understand more directly the tissue defect in osteogenesis imperfecta (OI),
      bone matrix was analyzed from an infant with lethal OI (type II) of defined
      mutation (collagen alpha 2(I)Gly580-->Asp). Pepsin-solubilized alpha 1(I) and
      alpha 2(I) chains and derived CNBr-peptides migrated more slowly on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis compared with normal human
      controls. The peptide alpha 2(I)CB3,5, predicted to contain the mutation site,
      ran as a retarded doublet band and was purified by high performance liquid
      chromatography and digested with V8 protease. Two peptides with amino-terminal
      sequences beginning at residue 576 of the alpha 2(I) chain were isolated. One had
      the normal sequence. The other differed in that aspartic acid replaced glycine at
      residue 580 as predicted from cDNA analysis, and in having an unhydroxylated
      proline at residue 579. From yields on microsequencing and the relative
      intensities of the two forms of alpha 2(I)CB3,5 on SDS-polyacrylamide gel
      electrophoresis, the ratio of mutant to normal alpha 2(I) chains in the infant's
      bone matrix was 0.7/1. Although the effects of an efficient incorporation of
      mutant chains on the properties of the bone matrix are unknown, it may be that in
      this OI case the tissue abnormalities result more from the presence of mutant
      protein than from an underexpression of matrix.

PMID- 1385414
TI  - Laminin B1 expression is required for laminin deposition into the extracellular
      matrix of PC12 cells.
AB  - The extracellular matrix of rat pheochromocytoma PC12 cells was shown by indirect
      immunofluorescence to consist of a network of fibronectin. The matrix did not
      contain laminin. The cells synthesized messenger RNA for fibronectin, laminin B2,
      and s-laminin but not for entactin or the B1 and A chains of laminin. Laminin B2
      but not laminin B1 was detectable in the culture medium and in cell lysates. A
      full-length cDNA clone for the B1 chain of laminin was constructed in the plasmid
      p-444, which contains the neomycin-resistance marker and human beta-actin
      promoter. PC12 cells were transfected with this recombinant plasmid, and stable
      neomycin-resistant clones were isolated and characterized. Clones that
      synthesized laminin B1 messenger RNA were found to deposit a laminin-containing
      matrix. In many of these clones the deposition of the fibronectin matrix was
      greatly diminished. The laminin matrix was predominantly localized in the
      intercellular spaces forming a honeycomb pattern. The morphology of the laminin
      synthesizing transfected cells was markedly different from the parental cells.
      The cells grew in tight clusters that were resistant to dissociating agents. It
      is concluded that the B1 chain of laminin contains information that is required
      for the formation of a stable laminin-containing extracellular matrix network
      either by interaction with cell surface receptors or other extracellular matrix
      components. Furthermore, expression of the laminin B1 gene may be a central
      regulatory point in determining extracellular matrix composition during
      embryogenesis.

PMID- 1385415
TI  - Protein synthesis at the blood-brain barrier. The major protein secreted by
      amphibian choroid plexus is a lipocalin.
AB  - Among the proteins secreted by choroid plexus of vertebrates, one protein is much
      more abundant than all others. In mammals, birds, and reptiles this protein is
      transthyretin, a tetramer of identical 15-kDa subunits. In this study choroid
      plexus from frogs, tadpoles, and toads incubated in vitro were found to
      synthesize and secrete one predominant protein. However, this consisted of one
      single 20-kDa polypeptide chain. It was expressed throughout amphibian
      metamorphosis. Part of its amino acid sequence was determined and used for
      construction of oligonucleotides for polymerase chain reaction. The amplified DNA
      was used to screen a toad choroid plexus cDNA library. Full-length cDNA clones
      were isolated and sequenced. The derived amino acid sequence for the encoded
      protein was 183 amino acids long, including a 20-amino acid presegment. The
      calculated molecular weight of the mature protein was 18,500. Sequence comparison
      with other proteins showed that the protein belonged to the lipocalin
      superfamily. Its expression was highest in choroid plexus, much lower in other
      brain areas, and absent from liver. Since no transthyretin was detected in
      proteins secreted from amphibian choroid plexus, abundant synthesis and secretion
      of transthyretin in choroid plexus must have evolved only after the stage of the
      amphibians.

PMID- 1385416
TI  - Structure and chromosomal localization of the human gene for a brain form of
      prostaglandin D2 synthase.
AB  - We have cloned and characterized the human gene for the 21-kDa brain form of
      prostaglandin D2 synthase. The gene was isolated from a human genomic lambda
      library and spans 3600 base pairs. It consists of seven exons and six introns.
      Southern blot analysis indicates that there is a single copy of the gene in the
      haploid genome. The transcriptional start site was mapped to a G residue 74 base
      pairs 5' of the ATG initiation codon. A TATA box-like element (ATAAATA) is
      situated 21 base pairs upstream of the mRNA start site. The gene was mapped to
      chromosome 9 bands q34.2-q34.3. The gene bears close resemblance to the genes for
      murine major urinary protein and ovine beta-lactoglobulin.

PMID- 1385417
TI  - Isolation and sequence of the cDNAs encoding the subunits of the isozyme form of
      wheat protein synthesis initiation factor 4F.
AB  - The nucleotide sequences of the cDNAs for the two subunits, p82 and p28, of the
      isozyme form of wheat germ eukaryotic initiation factor 4F (eIF-(iso)4F) were
      determined. The cDNA for the p82 subunit encodes a polypeptide of 86,514 Da. The
      deduced amino acid sequence of p82 contains possible motifs for ATP binding,
      metal binding, and phosphorylation. The cDNA sequence for the small subunit, p28,
      which is a m7G cap-binding protein, encodes a polypeptide of 23,524 Da. The
      deduced amino acid sequence of p28 is similar (approximately 38%) to cap-binding
      proteins from yeast and mammals. The p28 of wheat eIF-(iso)4F does not contain a
      serine or threonine in the vicinity of the serine (Ser53) of mammalian cap
      binding protein which is phosphorylated and shown to affect activity in mammalian
      cells.

PMID- 1385418
TI  - Characterization of a Ca2+ binding and regulatory site in the Ca2+ release
      channel (ryanodine receptor) of rabbit skeletal muscle sarcoplasmic reticulum.
AB  - A region in the skeletal muscle ryanodine receptor between amino acids 4014 and
      4765 was expressed as a trpE fusion protein. Overlay studies revealed that this
      region bound Ca2+ and ruthenium red, an indicator of Ca(2+)-binding sites. Ca2+
      binding was mapped to subregion 13b between amino acids 4246 and 4377,
      encompassing a predicted high affinity Ca(2+)-binding site, and to subregion 13c
      between amino acids 4364 and 4529, encompassing two predicted high affinity
      Ca(2+)-binding sites. Ca2+ binding was then mapped to three shorter sequences,
      22(13b1), 36(13c1), and 35(13c2), amino acids long, each encompassing one of the
      three predicted Ca(2+)-binding sites. Site-directed polyclonal antibodies were
      raised against these three short sequences and purified on antigen affinity
      columns. The antibody against sequence 13c2, lying between residues 4478 and
      4512, specifically recognized both denatured and native forms of the ryanodine
      receptor, suggesting that at least part of the 35 amino acid sequence containing
      the Ca(2+)-binding site is surface-exposed. The affinity purified antibody
      increased the Ca2+ sensitivity of ryanodine receptor channels incorporated into
      planar lipid bilayers, resulting in increased open probability and opening time
      without altering channel conductance. The antibody-activated channel was still
      modulated by Ca2+, Mg2+, ATP, ryanodine, and ruthenium red. These observations
      suggest that sequence 13c2 may be involved in Ca(2+)-induced Ca2+ release.

PMID- 1385419
TI  - Structural organization of the human insulin receptor ectodomain.
AB  - To provide an experimental system amenable to a detailed biochemical and
      structural investigation of the extracellular (ligand binding) domain of the
      insulin receptor, we developed a mammalian heterologous cell expression system
      from which tens of milligrams of the soluble secreted ectodomain (the IR921
      protein) can be routinely purified using methods that do not require harsh
      elution conditions. The purified IR921 protein has a Stokes radius of 6.8 nm and
      a sedimentation coefficient of 9.8 S, from which we calculate a hydro-dynamic
      mass of 281 kDa. Electron microscopic images, using both rotary shadowing and
      negative staining techniques, demonstrate a characteristic substructure for the
      IR921 protein consisting of two elongated arms, with a globular domain at each
      end, connected to each other at a point somewhat off-center to form a Y
      structure. Analysis using circular dichroism and fluorescence spectroscopy
      illustrate that insulin binding results in conformational changes in the
      ectodomain. Furthermore, fluorescence anisotropy decay data reveal segmental
      mobility within the IR921 protein that is successively frozen as a result of
      insulin binding, in contrast to results obtained in a previous study of the
      epidermal growth factor receptor ectodomain. This result suggests a divergence in
      hormone-induced signaling mechanisms used by the insulin and epidermal growth
      factor receptors.

PMID- 1385420
TI  - Growth hormone (GH) induction of tyrosine phosphorylation and activation of
      mitogen-activated protein kinases in cells transfected with rat GH receptor cDNA.
AB  - The mechanism of growth hormone (GH) action was studied in Chinese hamster ovary
      (CHO) cells transfected with GH receptor cDNA. Cytosolic extracts from GH- or
      phorbol ester (12-O-tetradecanoyl 4 beta-phorbol 13-acetate)-treated cells,
      transfected with full-length GH receptor cDNA, had an enhanced ability to
      phosphorylate myelin basic protein. Myelin basic protein, a substrate for mitogen
      activated protein (MAP) kinase, was maximally phosphorylated using extracts from
      cells treated with 50 nM bovine GH for 10 min. In addition, GH treatment resulted
      in an increased cell proliferation by 30-60%. GH and 12-O-tetradecanoyl 4 beta
      phorbol 13-acetate cause tyrosine phosphorylation of two proteins with M(r) of
      40,000 and 42,000 that are also recognized by MAP kinase antibodies. These
      proteins were identified as MAP kinases by analyzing phosphotyrosine
      immunoprecipitates on Western blots using MAP kinase antibodies. In addition, GH
      induces mitogenicity, as well as MAP kinase activation, in CHO cells expressing a
      receptor in which 184 amino acids had been deleted in the carboxyl-terminal part
      of the intracellular domain. No GH effects were seen in untransfected cells, in
      CHO cells expressing a truncated GH receptor containing only 5 of 349 amino acids
      in the intracellular domain, or in cells expressing the soluble GH-binding
      protein. In conclusion, our data show that GH treatment of CHO cells,
      reconstituted with GH receptors, initiates a phosphorylation cascade which
      includes MAP kinase.

PMID- 1385421
TI  - Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in
      macrophages in response to colony stimulating factor-1.
AB  - An approximately 64-kDa cytoplasmic protein is rapidly phosphorylated in tyrosine
      in the response of macrophages to colony stimulating factor-1. To identify this
      protein, BAC1.2F5 macrophages were incubated with or without colony stimulating
      factor-1, the phosphotyrosine-containing portion of their cytosolic fractions
      subjected to size exclusion chromatography, and the 45-70-kDa fraction further
      fractionated by reverse phase high pressure liquid chromatography (RP-HPLC).
      Tryptic peptides of pooled RP-HPLC fractions from stimulated cells (containing
      the approximately 64-kDa protein and an approximately 54-kDa protein) and from
      unstimulated cells (containing the approximately 54-kDa protein alone), were
      sequenced directly. All seven readable sequences of 8 sequenceable peptides
      present uniquely in the stimulated fraction were present in the sequence of the
      src homology 2 domain-containing protein tyrosine phosphatase-1C (PTP-1C). The
      identity of the approximately 64-kDa protein was confirmed by Western blotting
      with an antibody raised to a PTP-1C peptide. The rapid, growth factor-induced
      tyrosine phosphorylation of PTP-1C suggests that it may be involved in very early
      events in growth factor signal transduction.

PMID- 1385422
TI  - Stretch-induced parathyroid hormone-related peptide gene expression in the rat
      uterus.
AB  - We previously observed a peak in parathyroid hormone-related peptide (PTHrP) mRNA
      expression in preterm rat myometrium and found that this peak was dependent on
      intrauterine occupancy. We explored the possibility that mechanotransduction
      might control PTHrP gene expression in the uterus. This was done by developing an
      intrauterine balloon system that allowed us to reproduce experimentally the
      mechanical effects of the fetal pup in utero. An increase in PTHrP mRNA in the
      unoccupied horn of a unilaterally pregnant rat could be elicited as rapidly as 1
      h after balloon inflation and was maintained for up to 72 h. The same response
      was seen in uterine horns from virgin animals and could be reproduced by three
      different methods of imposing a physical stretch. Balloon-induced stretch also
      increased mRNA expression in a muscle bath system in vitro. Mechanotransduction
      appears to be largely, if not entirely, responsible for the preterm peak in PTHrP
      mRNA expression.

PMID- 1385423
TI  - Retinoblastoma protein dephosphorylation induced by D-erythro-sphingosine.
AB  - The retinoblastoma gene product (Rb), a nuclear phosphoprotein, functions as a
      tumor suppressor that is inactivated in retinoblastoma and other malignancies.
      The hypophosphorylated forms of Rb are observed in the G0/G1 phase of the cell
      cycle, whereas the hyperphosphorylated forms predominate in S and G2/M phases,
      suggesting that phosphorylation/dephosphorylation of Rb may regulate progression
      through the growth cycle. However, little is known about the intracellular
      signals that regulate phosphorylation/dephosphorylation of Rb. We show that D
      erythro-sphingosine potently induces early dephosphorylation of Rb. Initial
      dephosphorylation was observed as early as 1 h after treatment of hematopoietic
      cells with sphingosine, whereas complete shift to the dephosphorylated form was
      seen 4 h after treatment. These effects occurred at concentrations of sphingosine
      as low as 100-500 nM, with maximal effects observed at 1-2.5 microM. These
      effects were specific to sphingosine, inasmuch as other lipids, amphiphiles, and
      long chain amino bases, as well as structural analogs of sphingosine, failed to
      induce dephosphorylation of Rb. Also, activation of second messenger systems
      including protein kinase C, cAMP-dependent kinases, and calcium ionophores, as
      well as inhibition of serine/threonine protein phosphatases, failed to induce
      dephosphorylation of Rb. Induction of Rb dephosphorylation by sphingosine
      preceded inhibition of growth and a specific arrest in the G0/G1 phase of the
      cell cycle. These studies, for the first time, identify an intracellular
      activator of Rb.

PMID- 1385424
TI  - Transport of organic substrates via a volume-activated channel.
AB  - We have investigated the volume-activated transport of organic solutes in
      flounder erythrocytes. Osmotic swelling of cells suspended in a Na(+)-free medium
      led to increased membrane transport of taurine, glucose, and uridine. For each
      compound there was a significant lag period (1-2 min at 10 degrees C) between
      cell swelling and activation of the flux. The volume-activated fluxes of each of
      the substrates increased in parallel with increasing cell volume, and those of
      taurine and uridine increased linearly with concentration (up to 19 mM). The
      volume-activated fluxes of each of the three compounds showed similar
      sensitivities to a number of anion-selective channel blockers (5-nitro-2-(3
      phenylpropylamino)benzoic acid > 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid approximately MK-196 > niflumic acid > furosemide); the IC50 for the
      inhibition of the volume-activated fluxes by NPPB was around 12 microM. The
      results are consistent with the hypothesis that the volume-activated transport of
      organic osmolytes is via a pathway with the characteristics of a volume-activated
      "chloride channel." This raises the question of whether the transport of organic
      substrates might represent a physiological role for such channels in other cell
      types.

PMID- 1385425
TI  - Cooperative interactions among subunits of a voltage-dependent potassium channel.
      Evidence from expression of concatenated cDNAs.
AB  - Four copies of the coding sequence for a voltage-dependent potassium channel
      (RBK1, rat Kv1.1) were ligated contiguously and transcribed in vitro. The
      resulting RNA encodes four covalently linked subunit domains ([4]RBK1). Injection
      of this RNA into Xenopus oocytes resulted in the expression of voltage-dependent
      potassium currents. A single amino acid substitution, Tyr-->Val, located within
      the outer mouth of the pore, introduced into the equivalent position of any of
      the four domains, reduced affinity for external tetraethylammonium by
      approximately the same amount. In constructs containing 0, 1, 2, 3, or 4 Tyr
      residues the free energy of binding tetraethylammonium was linearly related to
      the number of Tyr residues. A different amino acid substitution, Leu-->Ile,
      located in the S4 region, was made in the equivalent position of one, two, three,
      or four domains. The depolarization required for channel activation increased
      approximately linearly with the number of Ile residues, whereas models of
      independent gating of each domain predict marked nonlinearity. Expression of this
      concatenated channel provides direct evidence that voltage-dependent potassium
      channels have four subunits positioned symmetrically around a central permeation
      pathway and that these subunits interact cooperatively during channel activation.

PMID- 1385426
TI  - Regulation of phosphoinositide kinases in T cells. Evidence that
      phosphatidylinositol 3-kinase is not a substrate for T cell antigen receptor
      regulated tyrosine kinases.
AB  - A phosphoinositide kinase that can phosphorylate phosphatidylinositol (PtdIns) is
      present in 4G10 monoclonal antibody (mAb) phosphotyrosine immunoprecipitates
      isolated from T cells activated via the T cell antigen receptor (TCR).CD3
      complex. This PtdIns kinase is not the PtdIns 3-kinase that associates with
      activated protein tyrosine kinases in fibroblasts, since Western blotting and
      immunoprecipitation experiments with antibodies specific for the p85 alpha
      subunit of the PtdIns 3-kinase indicate that this polypeptide is not
      immunoprecipitated by the 4G10 mAb from TCR.CD3-activated Jurkat cells. Moreover,
      immunoprecipitated PtdIns 3-kinase isolated from T cells with p85 antibodies is
      inhibited when PtdIns is presented in Nonidet P-40, whereas the PtdIns kinase
      activity present in 4G10 mAb phosphotyrosine immunoprecipitates is enhanced in
      the presence of Nonidet P-40. In vitro kinase assays of PtdIns 3-kinase
      immunoprecipitated with p85 antibodies from T cells indicate that it associates
      with a serine kinase that can phosphorylate a p85 polypeptide. However, no
      protein tyrosine kinase activity capable of tyrosine phosphorylating p85 in vitro
      associates with p85 alpha immunoprecipitates in quiescent or TCR.CD3-activated T
      cells. These data suggest that the TCR.CD3 complex does not regulate PtdIns 3
      kinase activity by a mechanism that involves protein tyrosine kinases.

PMID- 1385427
TI  - Angiotensin II regulates tenascin gene expression in vascular smooth muscle
      cells.
AB  - Angiotensin II, a vasoactive peptide, has been implicated in the pathophysiology
      of a number of vascular wall abnormalities. Since aberrant extracellular matrix
      deposition contributes to the pathogenesis of vessel wall disease, we examined
      the potential involvement of angiotensin II in the regulation of extracellular
      matrix synthesis by vascular smooth muscle cells. Immunoprecipitation of newly
      synthesized matrix proteins showed that, under serum-free conditions, cultured
      vascular smooth muscle cells constitutively produced high levels of fibronectin,
      small amounts of laminin, and a barely detectable amount of tenascin. Angiotensin
      II treatment increased synthesis of a 230-kDa tenascin glycoprotein by 9-fold and
      fibronectin synthesis by only 30-40% during a 24-h treatment period, without
      stimulating laminin production or a general increase in the synthesis of secreted
      proteins. Concomitant treatment with saralasin, a competitive inhibitor of
      angiotensin II, prevented the stimulation observed with angiotensin II. The
      stimulation of immunoprecipitable tenascin was preceded by an increase in
      tenascin mRNA. Levels of tenascin transcripts (8.4 and 7.0 kilobase) were
      significantly increased within 2 h after angiotensin II treatment, reached a
      maximum (10- to 12-fold) by 4 h, and remained elevated after 18 h. The induction
      was completely blocked by actinomycin D. Serum also induced tenascin mRNA, but
      with a different time course. Serum induction of tenascin mRNA was also evident
      at 2 h, maximal at 4 h, but declined to control levels at 8 h. These results
      indicate that angiotensin II exerts a rapid and selective stimulation of tenascin
      biosynthesis, at least in part at a transcriptional level. This suggests that
      angiotensin II may alter the composition of the extracellular matrix of the
      vessel wall by stimulating synthesis of the antiadhesive protein tenascin.

PMID- 1385428
TI  - Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice
      confers protection from oxygen injury.
AB  - To test directly whether mitochondrial Mn-superoxide dismutase (Mn-SOD) protects
      the lung epithelium from oxygen-induced injury, transgenic mice were produced in
      which the expression of human Mn-SOD mRNA was directly by transcriptional
      elements from the human pulmonary surfactant protein C gene. Human Mn-SOD mRNA
      was expressed in a lung-specific manner, and increased Mn-SOD protein was
      detected within mitochondria of alveolar Type II and nonciliated bronchiolar
      cells of the distal respiratory epithelium of the transgenic mice. The activity
      of Mn-SOD, but not catalase, CuZn-SOD, or glutathione peroxidase, was increased
      in lungs of transgenic mice. Transgenic mice were highly protected from lung
      injury during exposure to 95% oxygen, surviving significantly longer than
      nontransgenic littermates. Pulmonary pathology demonstrated decreased hemorrhage,
      hyaline membrane formation, and alveolar and interstitial edema in transgenic
      animals. The finding that increased Mn-SOD in distal respiratory epithelial cells
      confers protection from oxygen injury provides a basis for novel therapies to
      protect lung from injury during oxygen therapy of acute and chronic lung
      diseases.

PMID- 1385429
TI  - Identification of nuclear encoded precursor tRNAs within the mitochondrion of
      Trypanosoma brucei.
AB  - RNAs that function in mitochondria are typically encoded by the mitochondrial
      DNA. However, the mitochondrial tRNAs of Trypanosoma brucei are encoded by the
      nuclear DNA and therefore must be imported into the mitochondrion. It is becoming
      evident that RNA import into mitochondria is phylogenetically widespread and is
      essential for cellular processes, but virtually nothing is known about the
      mechanism of RNA import. We have identified and characterized mitochondrial
      precursor tRNAs in T. brucei. The identification of mitochondrially located
      precursor tRNAs clearly indicates that mitochondrial tRNAs are imported as
      precursors. The mitochondrial precursor tRNAs hybridize to cloned nuclear tRNA
      genes, label with [alpha-32P]CTP using yeast tRNA nucleotidyltransferase and in
      isolated mitochondria via an endogenous nucleotidyltransferase-like activity, and
      are processed to mature tRNAs by Escherichia coli and yeast mitochondrial RNase
      P. We show that T. brucei mitochondrial extract contains an RNase P activity
      capable of processing a prokaryotic tRNA precursor as well as the T. brucei tRNA
      precursors. Precursors for tRNA(Asn) and tRNA(Leu) were detected on Northern
      blots of mitochondrial RNA, and the 5' ends of these RNAs were characterized by
      primer extension analysis. The structure of the precursor tRNAs and the
      significance of nuclear encoded precursor tRNAs within the mitochondrion are
      discussed.

PMID- 1385430
TI  - Characterization of a 97-kDa phosphotyrosylprotein regulated by multiple
      cytokines.
AB  - We have examined the signal transduction pathways of a number of cytokines that
      interact with receptors that are members of the hematopoietin receptor
      superfamily. A 97-kDa protein was phosphorylated on tyrosine in response to
      stimulation of appropriate target cells with interleukin (IL)-2, IL-3,
      granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, or
      erythropoietin. These data suggest that a 97-kDa phosphotyrosylprotein represents
      a point of convergence for signal transduction by a number of growth factor
      receptors that do not have homology with any known protein tyrosine kinase. To
      address the possibility that p97 may represent a tyrosine kinase involved in
      multiple signal transduction pathways, we tested the capacity of this protein to
      bind a tyrosine kinase substrate or ATP. Indeed, a 97-kDa phosphotyrosylprotein
      purified from IL-2-stimulated lymphoid cells as well as granulocyte-macrophage
      CSF-stimulated myeloid cells bound to a polymer of glutamic acid and tyrosine
      which is a tyrosine kinase substrate. Further, a 97-kDa phosphotyrosylprotein
      present in both lineages also bound 8-azido-ATP. These data indicate that a 97
      kDa phosphotyrosylprotein with properties consistent with those of a protein
      tyrosine kinase is involved in the signal transduction pathways of certain
      members of the newly identified hematopoietin receptor superfamily and may
      represent an early point of convergence in the stimulus-response coupling of
      multiple cytokine receptors.

PMID- 1385431
TI  - Promoter region of the human alpha 2A adrenergic receptor gene.
AB  - In order to locate the promoter region of the human alpha 2A adrenergic receptor
      gene we used RNase protection analysis and antisense RNA probes to map the cap
      site of the alpha 2 transcripts. Prior sequence analysis has shown two potential
      TATA box motifs in the human alpha 2A adrenergic receptor gene, TATATAT and
      TATAAAA, located 427 and 1037 base pairs (bp), respectively, upstream of the
      protein coding region. RNase protection experiments and primer extension show
      that transcription starts downstream of the distal TATAAAA, indicating that the
      5'-untranslated region is approximately 1 kilobase in length. We have used the
      chloramphenicol acetyltransferase reporter gene and transient transfection into
      HT29, a human adenocarcinoma cell line that expresses the alpha 2A receptor, to
      show that as little as 150 bp upstream of the cap site can direct transcription.
      Sequence analysis shows that although this region contains the TATA box motif it
      lacks a CCAAT box motif. DNase I footprint analysis of a fragment from -17 to 
      193 (where +1 is the transcription initiation site), using nuclear extracts from
      HT29, showed hypersensitive sites (-68/-69) and two protected regions: -70 to 
      87, which includes a 10-bp palindrome, and -92 to -105, which includes a GC box,
      a common motif for Sp1 nuclear factor binding. Gel mobility shift assays indicate
      that Sp1 or a related factor may bind to this GC box. Deletion of the GC box and
      the palindrome from chloramphenicol acetyltransferase constructs abolishes
      transcription. We propose that these cis sequences may function in lieu of a
      CCAAT box to regulate transcription of the human alpha 2A adrenergic receptor
      gene.

PMID- 1385432
TI  - Selective tissue distribution of G protein gamma subunits, including a new form
      of the gamma subunits identified by cDNA cloning.
AB  - The GTP-binding regulatory proteins (G proteins) that transduce signals from
      receptors to effectors are composed of alpha, beta, and gamma subunits. Whereas
      the role of alpha subunits in directly regulating effector activity is widely
      accepted, it has recently been demonstrated that beta gamma subunits may also
      directly regulate effector activity. This has made clear the importance of
      identifying and characterizing beta and gamma subunits. We have isolated a cDNA
      clone encoding a new gamma subunit, referred to here as the gamma 7 subunit,
      using probes based on peptide sequences of a gamma subunit previously purified
      from bovine brain. The clone contains a 1.47-kilobase cDNA insert, which includes
      an open reading frame of 204 base pairs that predicts a 68-amino acid polypeptide
      with a calculated M(r) of 7553. The predicted protein shares amino acid
      identities with the other known gamma subunits, ranging from 38 to 68%. Also
      characteristic of gamma subunits is a carboxyl-terminal CAAX motif. The
      expression of the gamma 7 subunit as well as the gamma 2, gamma 3, and gamma 5
      subunits was examined in several bovine tissues at both the mRNA and protein
      levels. Whereas the gamma 2 and gamma 3 subunits were selectively expressed in
      brain, the gamma 5 and gamma 7 subunits were expressed in a variety of tissues.
      Thus, the gamma 5 and gamma 7 subunits are the first G protein gamma subunits
      known that could participate in the regulation of widely distributed signal
      transduction pathways.

PMID- 1385433
TI  - Cleavage of membrane-anchored growth factors involves distinct protease
      activities regulated through common mechanisms.
AB  - The membrane-anchored forms of transforming growth factor-alpha (TGF-alpha) and
      stem cell growth factors (Kit ligands) KL-1 and KL-2 are converted to soluble
      growth factor forms by a regulated proteolytic cleavage process. Each of these
      proteins is cleaved at a distinct site, however their cleavage is activated via a
      common set of intracellular signaling mechanisms. By using a panel of protease
      inhibitors, we show here that at least two cell-associated serine protease
      activities with distinct specificities participate in membrane growth factor
      cleavage. Two serine protease inhibitors of broad specificity,
      diisopropylfluorophosphate and 3,4-dichloroisocoumarin, prevent the cleavage of
      proTGF-alpha and KL-1 but not that of KL-2. Of the agents tested, N-tosyl-L
      phenylalanine chloromethyl ketone and various haloenol lactone derivatives are
      the most potent inhibitors of cleavage of all three membrane growth factors. It
      is concluded that cleavage of membrane-anchored growth factors involves a
      proteolytic system with multiple serine protease activities regulated through
      common mechanisms.

PMID- 1385434
TI  - Interferon alpha induces rapid tyrosine phosphorylation of the alpha subunit of
      its receptor.
AB  - The mechanisms of generation of second messengers after binding of interferon
      alpha (IFN alpha) to its receptor remain unknown. We have studied the
      phosphorylation of the alpha subunit of the IFN alpha receptor, which is
      recognized by the monoclonal antibody IFNa receptor 3. Immunoblotting experiments
      showed that IFN alpha induced rapid tyrosine phosphorylation of the alpha subunit
      in the IFN alpha-sensitive H-929, U-266, and Daudi cell lines.
      Immunoprecipitation experiments performed with 32P-labeled cells showed that the
      alpha subunit is phosphorylated before IFN alpha treatment and that the level of
      phosphorylation increases after IFN alpha stimulation. Phosphoamino acid analysis
      confirmed the IFN alpha-induced tyrosine phosphorylation and demonstrated that
      the base-line phosphorylation corresponded to serine phosphorylation that
      increased 50% upon IFN alpha treatment. Tyrosine phosphorylation of the alpha
      subunit was time- and dose-dependent, further demonstrating the specificity of
      the process. Phosphorylation of the alpha subunit of the receptor occurred
      rapidly after IFN alpha binding, both at 37 and 4 degrees C. Exposure of the
      cells to the tyrosine kinase inhibitor genistein blocked the IFN alpha-induced
      tyrosine phosphorylation of this subunit of the IFN alpha receptor. In contrast
      H7, a specific protein kinase C inhibitor, and acute and chronic exposure to
      phorbol esters had no effect on tyrosine phosphorylation, suggesting that protein
      kinase C does not regulate the tyrosine phosphorylation of the alpha subunit of
      the IFN alpha receptor. No IFN alpha-induced tyrosine phosphorylation was
      observed in the IFN alpha-resistant U-937 cell line that expresses a variant IFN
      alpha receptor. Altogether these data suggest that tyrosine phosphorylation of
      the alpha subunit may play a role in the signal transduction pathway of IFN
      alpha.

PMID- 1385435
TI  - Tissue-specific expression in mammalian brain, heart, and muscle of S1, a member
      of the elongation factor-1 alpha gene family.
AB  - Elongation factor-1 alpha (EF-1 alpha) is an ubiquitous protein that functions in
      peptide elongation during mRNA translation. We previously reported the isolation
      of a rat S1 protein that is antigenically related to statin, a nonproliferation
      specific protein; this S1 gene shares a high degree of homology to EF-1 alpha. We
      constructed specific riboprobes to the two genes, based on the difference in the
      3' noncoding regions of both S1 and EF-1 alpha mRNAs. Northern analysis and RNase
      protection assays have revealed that S1 mRNA is present only in brain, heart, and
      muscle, while EF-1 alpha mRNA has been detected in all tissues surveyed so far.
      The same tissue specificity has been observed in mouse, suggesting that S1
      expression is conserved between these two mammalian species. S1 transcript was
      detected in late brain embryogenesis (day 20), but in lower amounts than in 3
      month-old adult brain. We show that the relative levels of both S1 and EF-1 alpha
      transcripts and their respective tissue abundances remain unchanged during the
      aging process. The function of S1 is not yet known; but these results suggest
      that it may be involved in specific control mechanisms for protein synthesis in
      tissues where cells (i.e. neurons and myocytes) are permanently locked in a state
      of nonproliferation.

PMID- 1385436
TI  - Prolactin receptor triggering. Evidence for rapid tyrosine kinase activation.
AB  - The mechanism of action of prolactin (PRL) has remained obscure despite the
      unveiling of the primary structure of PRL receptors. The present study
      demonstrates rapid PRL receptor-mediated tyrosine phosphorylation of at least
      three cellular proteins, designated p120, p97, and p40, in a rat T-lymphoma (Nb2
      11C) as revealed by antiphosphotyrosine immunoblotting. One of the phosphotyrosyl
      proteins, p120, co-purified with activated PRL receptor complexes obtained using
      either anti-ligand or anti-receptor antibodies. Furthermore, in vitro incubation
      of affinity-purified PRL receptor complexes from PRL-stimulated cells with ATP in
      the presence of a tyrosine phosphatase inhibitor, resulted in a 10-15-fold
      increase in the phosphotyrosine content of p120, as revealed by
      antiphosphotyrosine immunoblotting. Parallel experiments utilizing [gamma-32P]ATP
      confirmed a rapid and time-dependent incorporation of phosphate into p120 in the
      same affinity-purified PRL receptor complexes. These data provide strong evidence
      for the involvement of a tyrosine kinase in PRL signal transduction and suggest
      the presence of a tyrosine kinase within the activated PRL receptor complex.

PMID- 1385437
TI  - Haemodynamic effects of the calcium facilitator Bay K-8644 in rats following
      vascular calcium overload.
AB  - 1. The haemodynamic effects of the Ca2+ facilitator Bay K-8644 (Bay) were studied
      in a model of calcinosis induced by acute treatment with vitamin D3 and nicotine
      administration over 4 days with 13 days of recovery. 2. Calcium content of the
      left ventricular myocardium increased 8-9 fold, while aortic Ca2+ levels
      increased up to 12-fold in treated animals. There were minimal changes in the ECG
      and no change in the level of plasma alpha-hydroxy-butyrate-dehydrogenase, a
      cardiac specific enzyme which increases during ischaemia. Significant increases
      in pulse pressure (PP) were seen in anaesthetized and conscious calcinotic rats,
      with no increase in cardiac output index (DABF) or systemic vascular resistance.
      However, aortic rigidity (AORI) was significantly elevated in the calcinotic
      group under anaesthesia. 3. In both control and calcinotic rats, pressor
      responses to i.v. Bay were exclusively mediated by an increase in aortic blood
      flow (DABF) as lower body vascular resistance (TLBVR) did not change. The
      increase in DABF at low doses (0.1-1 microgram kg-1) of Bay probably resulted
      from an increase in venous return induced by the agonist, as Bay had little
      effect on cardiac contractility over this dose range (as estimated by left
      ventricular dp/dtmax) and did not cause tachycardia. At higher doses (10-1000
      micrograms kg-1), Bay significantly increased LV dp/dt. Bay caused dose-related
      increases in AORI in pithed calcinotic rats, but a decrease in AORI in control
      animals. 4. The calcinosis model, which incorporates a recovery period to obviate
      the acute effects of nicotine and/or vitamin D3 treatment, results in long-term
      tissue calcium accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385438
TI  - Effect of ruthenium red on the bronchoconstriction induced by capsaicin and by
      selective tachykinin receptor agonists in anaesthetized guinea-pig.
AB  - 1. The effect of systemic administration of ruthenium red on bronchospasm induced
      by acetylcholine, capsaicin or selective tachykinin receptor agonists ([Sar9]SP
      sulfone or [beta Ala8]-neurokinin A (NKA)-(4-10) for NK-1 and NK-2 receptors,
      respectively) was studied in anaesthetized guinea-pigs. 2. The bronchospasm
      induced by capsaicin was reduced by ruthenium red, which did not affect the
      response induced by acetylcholine. Atropine, which totally blocked the response
      to acetylcholine, also partially blocked the bronchospasm induced by capsaicin.
      3. The inhibitory action of atropine and ruthenium red on the bronchospasm
      produced by capsaicin was additive, independently from the order of
      administration of the two antagonists. 4. Ruthenium red induced an increase in
      [Sar9]SP sulfone-bronchospasm and a marked enhancement of the bronchomotor
      response to [beta Ala8]NKA-(4-10). This latter was antagonized by the prior
      administration of the selective NK-2 receptor antagonist MEN 10,376. 5.
      Pretreatment with guanethidine or propranolol increased the airway constriction
      induced by [beta Ala8]NKA-(4-10). Furthermore, pretreatment with guanethidine
      prevented the enhancement induced by ruthenium red, showing that activation of NK
      2 receptors influences the sympathetic bronchodilator drive to the airways. 6. It
      is concluded that ruthenium red antagonizes selectively the in vivo excitatory
      effect of capsaicin in guinea-pig airways. Furthermore, the additivity of the
      blocking action of ruthenium red and atropine indicates that two distinct
      mechanisms take place in bronchospastic response to i.v. capsaicin in this
      species.

PMID- 1385439
TI  - Contrasting effect of substance P on renal function and dopamine excretion in
      hydropaenic and volume expanded dogs.
AB  - 1. Substance P (SP) and dopaminergic nerves have been described in the kidney. In
      the brain, SP increases dopamine production. In the kidney, SP increases sodium
      excretion. 2. Intrarenal dopamine acts as an endogenous natriuretic hormone. It
      is possible that dopamine could mediate the natriuretic effect of SP. 3. We
      therefore studied the effect of the intrarenal arterial infusion of SP (0.1, 1.0,
      10 ng kg body wt-1 min-1) on mean arterial pressure (MAP), renal blood flow
      (RBF), glomerular filtration rate (GFR), urine flow rate (V), absolute (UNaV) and
      fractional (FENa) sodium excretion as well as dopamine and noradrenaline
      excretion in dogs. Since dopamine is not natriuretic in hydropaenic states,
      studies were performed during hydropaenic and saline loaded states. 4. During
      hydropaenia, SP increased RBF, GFR, and V in a dose-related fashion but did not
      alter UNaV or FENa. Urinary noradrenaline was not affected but urinary dopamine
      decreased with increasing doses of SP. MAP was not affected. 5. During saline
      loading, SP increased RBF, GFR, V, UNaV, and FENa in a dose-related fashion. Both
      urinary noradrenaline and urinary dopamine increased. The fractional excretion of
      sodium correlated with dopamine but not noradrenaline excretion. MAP was not
      affected. 6. The renal haemodynamic and functional effects of SP may be mediated
      by SP-associated increases in urinary dopamine.

PMID- 1385440
TI  - Beyond palliative chemotherapy: providing hope in an era of unrealistic
      expectations and medical-care rationing.

PMID- 1385441
TI  - Osteoclasts express high levels of pp60c-src in association with intracellular
      membranes.
AB  - Deletion of the c-src gene in transgenic mice by homologous recombination leads
      to osteopetrosis, a skeletal defect characterized by markedly deficient bone
      resorption (Soriano, P., C. Montgomery, R. Geske, and A. Bradley. 1991. Cell.
      64:693-702), demonstrating a critical functional role of pp60c-src in osteoclast
      activity. Since decreased bone resorption could result from a defect either
      within the osteoclast or within other cells present in its environment,
      indirectly affecting osteoclast functions, we determined which cell(s) in bone
      expressed high levels of pp60c-src Measuring pp60c-src protein and kinase
      activities in osteoclasts and immunolocalizing pp60c-src in bone, we find that
      expression of pp60c-src is nearly as high in osteoclasts as in brain and
      platelets. In contrast, other bone cells contain only very low levels of the
      protein. In addition, expression of the c-src gene product increases when bone
      marrow cells are induced to express an osteoclast-like phenotype by 1,25
      dihydroxy-vitamin D3, further suggesting that high expression of pp60c-src is
      part of the osteoclast phenotype. Three other src-like kinases, c-fyn, c-yes, and
      c-lyn, are also expressed in osteoclasts at ratios to pp60c-src similar to what
      is found in platelets. These src-related proteins do not, however, compensate for
      the absence of pp60c-src in the src- mice, thereby suggesting that pp60c-src may
      have a specific function in osteoclasts. Although further work is necessary to
      elucidate what the critical role of pp60c-src in osteoclasts is, our observation
      that the protein is associated mostly with the membranes of intracellular
      organelles suggests the possibility that this role might be at least in part
      related to the targeting or fusion of membrane vesicles.

PMID- 1385442
TI  - A new family of yeast nuclear pore complex proteins.
AB  - We have identified a novel family of yeast nuclear pore complex proteins. Three
      individual members of this family, NUP49, NUP100, and NUP116, have been isolated
      and then characterized by a combination of molecular genetics and
      immunolocalization. Employing immunoelectron and immunofluorescence microscopy on
      yeast cells, we found that the binding of a polyspecific monoclonal antibody
      recognizing this family was predominantly at the nuclear pore complexes.
      Furthermore, the tagging of NUP49 with a unique epitope enabled the
      immunolocalization of this protein to the nuclear pore complex by both
      fluorescence and electron microscopy. DNA sequence analysis has shown that the
      amino-terminal regions of NUP49, NUP100, and NUP116 share repeated "GLFG" motifs
      separated from each other by glutamine, asparagine, serine and threonine rich
      spacers. All three proteins lack a repetitive domain found in the two precisely
      described yeast nuclear pore complex proteins. Only NUP49 is essential for cell
      viability. NUP116-deficient cells grow very slowly and are temperature sensitive,
      whereas the lack of NUP100 has no detectable phenotype. NUP100 and NUP116 are
      homologous over their entire lengths. Interestingly, NUP100 and NUP116 are both
      flanked by a histidine tRNA gene and a transposon element suggesting that they
      may have arisen by gene duplication. We propose that subfamilies of pore complex
      proteins can be defined by their characteristic combinations of different modular
      domains.

PMID- 1385443
TI  - Proteins containing an uncleaved signal for glycophosphatidylinositol membrane
      anchor attachment are retained in a post-ER compartment.
AB  - Glycophosphatidylinositol (GPI)-anchored membrane proteins are initially
      synthesized with a cleavable COOH-terminal extension that signals anchor
      attachment. Overexpression in COS cells of hGH-DAF fusion proteins containing the
      GPI signal of decay accelerating factor (DAF) fused to the COOH-terminus of human
      growth hormone (hGH), produces both GPI-anchored hGH-DAF and uncleaved precursors
      that retain the GPI signal. Using hGH-DAF fusion proteins containing a mutated,
      noncleavable GPI signal, we show that uncleaved polypeptides are retained inside
      the cell and accumulate in a brefeldin A-sensitive, Golgi-like juxtanuclear
      structure. Retention requires the presence of either a functional or a
      noncleavable GPI signal; hGH-DAF fusion proteins containing only the COOH
      terminal hydrophobic domain (a component of the GPI signal) are secreted.
      Immunofluorescence analysis shows colocalization of the retained, uncleaved
      fusion proteins with both a Golgi marker and with p53, a marker of the ER-Golgi
      intermediate compartment. Since N-linked glycosylation is postulated to
      facilitate the transport of proteins to the cell surface, we engineered a
      glycosylation site into hGH-DAF. Glycosylation failed to completely override the
      transport block, but allowed some uncleaved hGH-DAF to pass through the secretory
      pathway and acquire endoglycosidase H resistance. The retained molecules remained
      endoglycosidase H sensitive. We suggest that the uncleaved fusion protein is
      retained in a sorting compartment between the ER and the medial Golgi complex. We
      speculate that a mechanism exists to retain proteins containing an uncleaved GPI
      signal as part of a system for quality control.

PMID- 1385444
TI  - Tyrosine phosphorylation of paxillin and pp125FAK accompanies cell adhesion to
      extracellular matrix: a role in cytoskeletal assembly.
AB  - Cells in culture reveal high levels of protein tyrosine phosphorylation in their
      focal adhesions, the regions where cells adhere to the underlying substratum. We
      have examined the tyrosine phosphorylation of proteins in response to plating
      cells on extracellular matrix substrata. Rat embryo fibroblasts, mouse Balb/c
      3T3, and NIH 3T3 cells plated on fibronectin-coated surfaces revealed elevated
      phosphotyrosine levels in a cluster of proteins between 115 and 130 kD. This
      increase in tyrosine phosphorylation was also seen when rat embryo fibroblasts
      were plated on laminin or vitronectin, but not on polylysine or on uncoated
      plastic. Integrin mediation of this effect was suggested by finding the same
      pattern of elevated tyrosine phosphorylation in cells plated on the cell-binding
      fragment of fibronectin and in cells plated on a synthetic polymer containing
      multiple RGD sequences. We have identified one of the proteins of the 115-130-kD
      cluster as pp125FAK, a tyrosine kinase recently localized in focal adhesions
      (Schaller, M. D., C. A. Borgman, B. S. Cobb, R. R. Vines, A. B. Reynolds, and J.
      T. Parsons. 1992. Proc. Natl. Acad. Sci. USA. 89:5192). A second protein that
      becomes tyrosine phosphorylated in response to extracellular matrix adhesion is
      identified as paxillin, a 70-kD protein previously localized to focal adhesions.
      Treatment of cells with the tyrosine kinase inhibitor herbimycin A diminished the
      adhesion-induced tyrosine phosphorylation of these proteins and inhibited the
      formation of focal adhesions and stress fibers. These results suggest a role for
      integrin-mediated tyrosine phosphorylation in the organization of the
      cytoskeleton as cells adhere to the extracellular matrix.

PMID- 1385445
TI  - Integrin-dependent phosphorylation and activation of the protein tyrosine kinase
      pp125FAK in platelets.
AB  - We have investigated mechanisms involved in integrin-mediated signal transduction
      in platelets by examining integrin-dependent phosphorylation and activation of a
      newly identified protein tyrosine kinase, pp125FAK (FAK, focal adhesion kinase).
      This kinase was previously shown to be localized in focal adhesions in
      fibroblasts, and to be phosphorylated on tyrosine in normal and Src-transformed
      fibroblasts. We show that thrombin and collagen activation of platelets causes an
      induction of tyrosine phosphorylation of pp125FAK and that pp125FAK molecules
      isolated from activated platelets display enhanced levels of phosphorylation in
      immune-complex kinase assays. pp125FAK was not phosphorylated on tyrosine after
      thrombin or collagen treatment of Glanzmann's thrombasthenic platelets deficient
      in the fibrinogen receptor GPIIb-IIIa, or of platelets pretreated with an
      inhibitory monoclonal antibody to GP IIb-IIIa. Fibrinogen binding to GP IIb-IIIa
      was not sufficient to induce pp125FAK phosphorylation because pp125FAK was not
      phosphorylated on tyrosine in thrombin-treated platelets that were not allowed to
      aggregate. These results indicate that tyrosine phosphorylation of pp125FAK is
      dependent on platelet aggregation mediated by fibrinogen binding to the integrin
      receptor GP IIb-IIIa. The induction of tyrosine phosphorylation of pp125FAK was
      inhibited in thrombin- and collagen-treated platelets preincubated with
      cytochalasin D, which prevents actin polymerization following activation. Under
      all of these conditions, there was a strong correlation between the induction of
      tyrosine phosphorylation of pp125FAK in vivo and stimulation of the
      phosphorylation of pp125FAK in vitro in immune-complex kinase assays. This study
      provides the first genetic evidence that tyrosine phosphorylation of pp125FAK is
      dependent on integrin-mediated events, and demonstrates that there is a strong
      correlation between tyrosine phosphorylation of pp125FAK in platelets, and the
      activation of pp125FAK-associated phosphorylating activity in vitro.

PMID- 1385446
TI  - A point mutation of integrin beta 1 subunit blocks binding of alpha 5 beta 1 to
      fibronectin and invasin but not recruitment to adhesion plaques.
AB  - A point mutation in a highly conserved region of the beta 1 subunit, Asp130 to
      Ala (D130A) substitution, abrogates the Arg-Gly-Asp (RGD)-dependent binding of
      alpha 5 beta 1 to fibronectin (FN) without disrupting gross structure or
      heterodimer assembly. The D130A mutation also interferes with binding to invasin,
      a ligand that lacks RGD sequence. In spite of the lack of detectable FN binding
      by alpha 5 beta 1(D130A), it was recruited to adhesion plaques formed on FN by
      endogenous hamster receptors. Thus, intact ligand binding function is not
      required for recruitment of alpha 5 beta 1 to adhesion plaques. Overexpression of
      beta 1(D130A) partially interfered with endogenous alpha 5 beta 1 function, thus
      defining a dominant negative beta 1 integrin mutation.

PMID- 1385447
TI  - Thrombin-induced expression of endothelial P-selectin and intercellular adhesion
      molecule-1: a mechanism for stabilizing neutrophil adhesion.
AB  - Thrombin-induced expression of endothelial adhesivity toward neutrophils (PMN)
      was studied using human umbilical vein endothelial cells (HUVEC). HUVEC were
      challenged with human alpha-thrombin for varying durations up to 120 min, after
      which the cells were fixed with 1% paraformaldehyde and 51Cr-labeled human PMN
      were added to determine PMN adhesion. Endothelial adhesivity increased within 15
      min after alpha-thrombin exposure, and the response persisted up to 120 min.
      Expression of endothelial adhesion proteins, P-selectin (GMP-140, PADGEM, CD62),
      and intercellular adhesion molecule-1 (ICAM-1; CD54) on the endothelial surface
      was quantitated by increase in the specific binding of anti-P-selectin mAb G1 and
      anti-ICAM-1 mAb RR1/1 labeled with 125I. P-selectin expression was maximal at 5
      15 min alpha-thrombin exposure and decayed to basal levels within 90 min. In
      contrast, ICAM-1 activity increased at 30 min and remained elevated for 120 min
      after alpha-thrombin challenge. The initial endothelial adhesivity was dependent
      on P-selectin expression since PMN adhesion occurring within the first 30 min
      after alpha-thrombin challenge was inhibited by mAb G1. The later prolonged PMN
      adhesion was ICAM-1 dependent since this response was inhibited by mAb RR1/1 and
      to the same degree by the anti-CD18 mAb IB4. Anti-ELAM-1 mAb BB11 had no effect
      on adhesion of PMN to the alpha-thrombin-challenged cells. The initial P-selectin
      expression and PMN adhesion responses were reproduced by the 14-amino peptide
      (SFLLRNPNDKYEPF) (thrombin-receptor activity peptide; TRP-14) which comprised the
      NH2 terminus created by thrombin's proteolytic action on its receptors. However,
      TRP-14-induced PMN adhesion was transient, and TRP-14 did not cause ICAM-1
      expression. The ICAM-1-dependent PMN adhesion mediated by alpha-thrombin was
      protein synthesis independent since ICAM-1 expression and PMN adhesion were not
      inhibited by cycloheximide pretreatment of HUVEC. Moreover, Northern blot
      analysis indicated absence of ICAM-1 mRNA signal up to 180 min after alpha
      thrombin challenge. In conclusion, thrombin-induced endothelial adhesivity
      involves early- and late-phase responses. The initial reversible PMN adhesion is
      mediated by rapid P-selectin expression via TRP-14 generation. Thrombin-induced
      PMN adhesion is stabilized by a protein synthesis-independent upregulation of the
      constitutive ICAM-1 activity which enables the interaction of ICAM-1 with the
      CD18 beta 2 integrin on PMN.

PMID- 1385450
TI  - Monoclonal antibody that recognizes the carbohydrate portion of cell adhesion
      molecule L1 influences calcium current in cultured neurons.
AB  - A monoclonal antibody (mAb), 2E12, against the neural cell adhesion molecule L1
      recognized the 200 kDa component of L1. The epitope of L1 reacting with mAb 2E12
      was localized in its carbohydrate chain, judging from the results of experiments
      on glycopeptidase F treatment. The physiological effect of adding mAbL1 (2E12) to
      cultured mouse dorsal root ganglion neurons was studied using patch-clamp
      techniques. The binding of mAbL1 (2E12) to the neurons expressing L1 molecule
      induced an inward current inhibited by calcium channel blockers such as
      nifedipine and Lanthanum. It was also found that the mAbL1 (2E12) leads to a rise
      in the intracellular Ca2+ concentration ([Ca2+]i) in cultured neurons. This rise
      seems to be due to an influx of extracellular Ca2+, since treatment with EGTA
      abolished those phenomena. L-type calcium channel blockers such as nifedipine and
      cadmium, as well as inward current, blocked the effect of mAbL1 (2E12). These
      results suggest that the carbohydrate chain of L1 glycoprotein is directly
      involved in the induction of calcium current, and that the L1 molecule may play a
      prominent role in regulation of the Ca2+ channel.

PMID- 1385448
TI  - Endothelial cells interact with the core protein of basement membrane perlecan
      through beta 1 and beta 3 integrins: an adhesion modulated by glycosaminoglycan.
AB  - Aortic endothelial cells adhere to the core protein of murine perlecan, a heparan
      sulfate proteoglycan present in endothelial basement membrane. We found that cell
      adhesion was partially inhibited by beta 1 integrin-specific mAb and almost
      completely blocked by a mixture of beta 1 and alpha v beta 3 antibodies.
      Furthermore, adhesion was partially inhibited by a synthetic peptide containing
      the perlecan domain III sequence LPASFRGDKVTSY (c-RGD) as well as by GRGDSP, but
      not by GRGESP. Both antibodies contributed to the inhibition of cell adhesion to
      immobilized c-RGD whereas only beta 1-specific antibody blocked residual cell
      adhesion to proteoglycan core in the presence of maximally inhibiting
      concentrations of soluble RGD peptide. A fraction of endothelial surface-labeled
      detergent lysate bound to a core affinity column and 147-, 116-, and 85-kD
      proteins were eluted with NaCl and EDTA. Polyclonal anti-beta 1 and anti-beta 3
      integrin antibodies immunoprecipitated 116/147 and 85/147 kD surface-labeled
      complexes, respectively. Cell adhesion to perlecan was low compared to perlecan
      core, and cell adhesion to core, but not to immobilized c-RGD, was selectively
      inhibited by soluble heparin and heparan sulfates. This inhibition by heparin was
      also observed with laminin and fibronectin and, in the case of perlecan, was
      found to be independent of heparin binding to substrate. These data support the
      hypothesis that endothelial cells interact with the core protein of perlecan
      through beta 1 and beta 3 integrins, that this binding is partially RGD
      independent, and that this interaction is selectively sensitive to a cell
      mediated effect of heparin/heparan sulfates which may act as regulatory ligands.

PMID- 1385451
TI  - Heat-induced transcription from RNA polymerases II and III and HSF binding
      activity are co-ordinately regulated by the products of the heat shock genes.
AB  - Heat shock leads to co-ordinate increases in transcription of a family of heat
      shock genes, including the mouse hsp70.1 and B2 genes. Activation of the heat
      shock transcription factor (HSF) by heat shock stimulates transcription of the
      murine hsp70.1 gene (by RNA polymerase II). B2 genes are short, repetitive
      sequences whose transcription (by RNA polymerase III) are also increased after
      heat shock. We have studied whether heat-induced transcription is auto-regulated
      by the products of the heat shock genes. The results indicate: (1) after an
      initial heat shock, transcription of the heat shock genes by RNA polymerases II
      and III becomes desensitized to further heat shock, and the heat-induced DNA
      binding activity of the HSF is lost, (2) if accumulation of heat shock gene
      products is inhibited, the desensitizing effect of a prior heat shock is removed,
      and (3) transcription of the hsp70.1 and B2 genes apparently involves different
      mechanisms, with hsp70.1 employing the HSF and the B2 gene using a separate, heat
      activated transcriptional mechanism. However, the level of transcription from the
      hsp70.1 and B2 genes and the stability of their respective RNAs are co-ordinately
      regulated by the level of heat shock protein in the cell. The data indicate that
      auto-regulation of the level of mouse heat shock gene products is mediated by RNA
      polymerase II transcripts but that the regulatory mechanism can control
      transcription from RNA polymerase III genes as well.

PMID- 1385452
TI  - Repetitive 5-azacytidine treatments of Fao cells induce a stable and strong
      expression of gamma-glutamyl transpeptidase.
AB  - The role of DNA methylation in the expression of the rat gamma-glutamyl
      transpeptidase (GGT) gene was assessed in the Fao cell line using a
      hypomethylating agent, 5-azacytidine. Ten repetitive treatments of the cells,
      with 8 microM 5-azacytidine for 24 h, led to 13- and 80-fold increases,
      respectively, in GGT activity and in GGT mRNA level. The DNA methylation patterns
      generated by the isoschizomeric restriction enzymes Hpa II and Msp I indicated
      that the GGT gene, highly methylated in Fao cells, became strongly demethylated
      after 5-azacytidine treatments. Thus, DNA demethylation increases the expression
      of the GGT gene. 5-Azacytidine treatments also increased, but to a lesser extent,
      mRNAs level for actin, albumin, mitochondrial aspartate aminotransferase,
      aldolase B mRNAs (12- to 16-fold) as well as for tubulin, gluthathione
      transferase, and tyrosine aminotransferase mRNAs (2- to 5-fold). The GGT gene
      expression was further studied in B4 cells, cloned from the demethylated Fao cell
      population. This clone B4 exhibited a stable and strong GGT activity and a highly
      demethylated GGT gene. Among the three GGT mRNA I, II, or III, transcribed from
      three different promoters of the single rat GGT gene, only mRNA III was detected
      in Fao cells and was increased in clone B4, indicating that the demethylation
      acts on the promoter for mRNA III. The analysis of the differentiation state of
      B4 cells, as compared to Fao cells, showed a loss of the regulation of GGT and
      aspartate aminotransferase genes by dexamethasone, as well as a loss of the
      gluconeogenic pathway. Interestingly, B4 cells have retained many other specific
      functions of hepatic differentiation and have acquired alpha-fetoprotein
      expression; thus this clone exhibits the characteristics of a hepatic fetal
      phenotype.

PMID- 1385449
TI  - Developmental changes in heparan sulfate expression: in situ detection with mAbs.
AB  - Two mAbs that are specific for heparan sulfate-related epitopes have been raised
      and used to analyze the cellular and tissular distribution of this
      glycosaminoglycan during development. mAb 10E4 reacts with an epitope that occurs
      in native heparan sulfate chains and that is destroyed by N-desulfation of the
      glycosaminoglycan. The antibody does not react with hyaluronate, chondroitin
      sulfate, or DNA, and reacts only poorly with heparin. The reactivity of
      proteoglycan extracts or tissue sections with the 10E4 antibody is completely
      abolished by heparitinase, but is only partially affected by heparinase. mAb
      3G10, in contrast, reacts only with heparitinase-treated heparan sulfate chains,
      proteoglycans, or tissue sections. The 3G10 epitope is destroyed by treatment
      with mercuric acetate, which indicates that the desaturated uronate generated by
      the lyase is essential for the reactivity of the antibody. The 3G10 epitope is
      not generated by treating heparan sulfate proteoglycans with heparinase or
      chondroitin sulfate proteoglycans with chondroitin sulfate lyases, which
      indicates that the 3G10 antibody recognizes desaturated uronates that occur in
      specific structural contexts. The antibody 10E4 and, after heparitinase
      treatment, the antibody 3G10 decorate the surfaces of many cell types and the
      extracellular matrix in proximity of the cells, in particular, the basement
      membranes. The analysis of embryonic and adult tissues reveals important temporal
      and regional differences in the abundance of the 10E4 and 3G10 epitopes at these
      sites. Moreover, the staining pattern of the two antibodies is not always
      superimposable, which is indicative of regional differences in the exposure or
      structure of the tissular heparan sulfates. As a whole the results suggest that
      heparan sulfate abounds at sites of active morphogenesis and that the expression
      of this glycosaminoglycan is developmentally regulated.

PMID- 1385453
TI  - Regulation of C-myc and C-Ha-ras oncogene expression by cell shape.
AB  - The influence of cell shape on the expression of proto-oncogenes was examined in
      normal and malignant human cells that varied in their sensitivities to contact
      inhibition of proliferation. Cells were constrained into varying degrees of
      roundness by plating onto culture surfaces coated with different concentrations
      of poly(2-hydroxyethyl methacrylate) (poly[HEMA]) and assayed for proliferation
      capacity and levels of c-myc, c-ras, c-fos, and c-fes mRNAs. Proliferation of
      contact-inhibited normal CUA-1 fibroblasts and the variant HT-IFNr cells was
      highly coupled to cell shape. As these cells became more rounded, a critical
      degree of roundness was reached at which proliferation ceased. In contrast,
      proliferation of non-contact-inhibited malignant HT-1080 cells was independent of
      cell shape. Northern analysis revealed that expression of c-myc and c-ras was
      highly sensitive to cell shape in the normal CUA-1 cells but not in the malignant
      HT-1080 or variant HT-IFNr cells. Levels of c-myc and c-ras mRNAs declined to
      nearly undetectable levels in CUA-1 cells at degrees of roundness that correlated
      with loss of proliferative ability. Expression of c-fos and c-fes oncogenes were
      independent of cell shape in all cells tested. Quantification of transcription
      rates by the nuclear run-off assay showed that shape modulation of c-myc and c
      ras oncogene expression occurred at the transcriptional level. These data suggest
      that changes in cell shape can modulate expression of certain oncogenes and that
      these changes correlate with the cell's ability to proliferate. Moreover,
      inability to regulate c-myc and c-ras oncogene expression is associated with loss
      of shape-dependent growth controls and contact inhibition but that loss of this
      regulation alone is not sufficient to release cells from contact-inhibited
      controls.

PMID- 1385454
TI  - A novel nuclear protein which binds to G gamma and A gamma globin promoters and
      modulates hemoglobin synthesis in K562 cells.
AB  - Nuclear extract of human erythroleukemic cell line K562 contains a 70 kDa protein
      which is gradually reduced when cells are induced to express globin genes by 25
      microM hemin. When globin synthesis was inhibited by cycloheximide (100
      micrograms/ml) or Actinomycin D (1 microgram/ml), the disappearance of this
      protein was prevented. The 70 kDa nuclear protein exhibited strong binding to G
      gamma and A gamma globin promoters but not to beta-globin promoter. This suggests
      that this 70 kDa nuclear protein may be involved in the regulation of fetal
      globin gene expression.

PMID- 1385456
TI  - Monoclonal antibodies identify a possible regulatory domain of MyoD1.
AB  - A panel of monoclonal antibodies (mAbs) to murine MyoD1 was generated. One set of
      mAbs is shown to react with epitope(s) in the cysteine/histidine-rich (C/H)
      region while another set is shown to react with epitope(s) in the C-terminal
      portion of MyoD1. One of the mAbs reactive with a C-terminal epitope sensitively
      detected MyoD1 in whole cell extracts by Western blotting. Time course studies of
      total protein accumulation during C2C12 myoblast differentiation revealed only
      subtle changes in the phosphorylation and quantity of MyoD1 protein present in
      C2C12 cells from induction to 120 hr after induction. These results suggest that
      modulation of MyoD1 protein or total phosphorylation levels is not tightly
      associated with the transition of undifferentiated myoblasts to differentiated
      myocytes. Monoclonal antibodies to the C-terminal epitope produced supershifted
      bands in gel retardation assays, indicating that these mAbs had no effect on DNA
      binding. Although the C/H region of MyoD1 does not participate in DNA binding,
      mAbs reactive with the C/H region neutralized this activity in gel retardation
      assays. These data suggest that the conserved C/H domain may serve to modulate
      MyoD1 DNA-binding activity by interacting with another regulator.

PMID- 1385455
TI  - Cytokine triggered molecular pathways that control cell cycle arrest.
AB  - Recent progress has been made concerning the understanding of the molecular
      pathways that mediate the growth suppressive effects of inhibitory cytokines.
      Interferons, interleukin-6 and transforming growth factor-beta were investigated
      in these studies. Cell lines that display growth sensitivity to all three
      cytokines and growth resistant derivates provided a suitable genetic background
      to determine whether common or unique post-receptor elements mediate the effects
      of each cytokine. Three nuclear genes, c-myc, RB, and cyclin A were found to be
      common key downstream targets along the cytokine induced growth suppressive
      pathways. Genetic and pharmacological manipulations proved that these molecular
      responses fall into few complementary pathways that function in parallel to
      achieve the cytokine mediated G0/G1 arrest. New strategies, such as knock out
      anti-sense gene cloning were developed and they currently provide powerful tools
      for the isolation of genes along the signaling pathways of growth arrest.

PMID- 1385458
TI  - Anti-fibronectin antibodies that modify heparin binding and cell adhesion:
      evidence for a new cell binding site in the heparin binding region.
AB  - A panel of monoclonal antibodies (mAbs) to bovine fibronectin (FN) is described
      which modulates either heparin binding or cell adhesion to FN, or both. A
      combination of competitive exclusion and binding to proteolytic fragments
      identified epitopes in the Hep II, Hep III/I and CBF (cell binding fragment)
      regions of FN. mAb A17, which bound to the CBF region, strongly inhibited the
      cell adhesion of BHK-21 fibroblasts, primary corneal fibroblasts and endothelial
      cells, and NM4 mammary adenocarcinoma cells, to FN at mAb concentrations as low
      as 1 microgram/ml. This mAb was not so effective at inhibiting the adhesion of
      B16 mouse melanoma cells. Adhesion of B16 cells to FN was more sensitive to
      inhibition by mAbs binding to Hep II (A2, A9, A32, A35). Of these, A32 and A35
      significantly increased the binding of 35S-heparin to FN, whereas A2 and A9 did
      not affect it. mAbs A2, A9 and A32 showed good binding to HBF, the 40 kDa
      proteolytic fragment of human FN which contains both Hep II and IIICS (type III
      connecting segment). These mAbs inhibited B16 cell adhesion to the HBF (heparin
      binding fragment) by 30-50%, the greatest inhibition being shown by mAb A32. Two
      synthetic peptides from the HBF, CS1 (peptide 1) from the IIICS region and
      peptide I from the Hep II region, also inhibited B16 cell adhesion to HBF by
      approximately 70 and 30%, respectively. These results suggest that maximal cell
      adhesion to the HBF involves both CS1 and Hep II. The inhibitory effects of the
      two peptides were linearly additive in combination, whereas the inhibitory mAbs
      A2, A9 and A32 showed synergistic additive effects with each of the peptides.
      This points to the existence of an additional important cell binding site in Hep
      II, other than peptide I. Recent independent evidence for an additional cell
      binding site in Hep II supports this view. Melanoma cellular receptor(s) for the
      Hep II region may be cell surface proteoglycans but do not appear to bind to
      areas of Hep II with high affinity for soluble heparin, as the latter was not an
      inhibitor of B16 cell adhesion to the HBF. The increased effectiveness of A32 in
      inhibiting cell adhesion, compared to A2 and A9, may be due to conformational
      effects which increase the binding of soluble heparin, but reduce affinity for
      the cellular receptor. These results are discussed in context with other reports
      in the literature.

PMID- 1385459
TI  - A complex consisting of pp60c-src/pp60c-srcN and a 38 kDa protein is highly
      enriched in growth cones from differentiated SH-SY5Y neuroblastoma cells.
AB  - Nerve growth cones of primary neurons are highly enriched in the proto-oncogene
      product pp60c-src. In order to investigate this molecule further in growing
      neuronal cells, growth cone and cell body fractions were prepared from human SH
      SY5Y neuroblastoma cells differentiated neuronally in vitro under the influence
      of phorbol ester. The fractions were characterized ultrastructurally and by
      biochemical criteria. The neuronal (pp60c-srcN) and the fibroblastic (pp60c-src)
      forms of pp60src are slightly enriched and activated in the growth cones relative
      to the perikarya. Immunoprecipitates of pp60src from differentiated SH-SY5Y
      growth cones contain at least four phosphoproteins in addition to pp60src. One of
      these, pp38, migrates as a 100-140 kDa complex with pp60src under non-reducing
      conditions of gel electrophoresis. The pp38/pp60src complex is not easily
      detected in non-differentiated SH-SY5Y cells or perikarya of differentiated SH
      SY5Y cells, but it is highly enriched in the growth cone preparation. These data
      suggest that growth-cone pp60src exists in a disulfide-linked oligomeric complex.
      The complex appears to be assembled only in the cell periphery and may be
      dependent upon neuronal differentiation.

PMID- 1385457
TI  - Total inhibition of involucrin synthesis by a novel two-step antisense procedure.
      Further examination of the relationship between differentiation and malignancy in
      hybrid cells.
AB  - A novel procedure involving the sequential use of two different antisense
      constructs has been used to inhibit the synthesis of involucrin in a hybrid cell
      line formed by the fusion of a human cervical carcinoma cell with a normal human
      keratinocyte (ESH100P6). In this cell line, and other similar hybrids,
      malignancy, as measured by progressive growth in vivo, is suppressed; and it has
      been shown that the keratinocyte imposes its own programme of terminal
      differentiation on the non-malignant hybrid cell. In particular, involucrin, a
      precursor of one of the major components of the cornified envelope of mature
      keratinocytes, continues to be produced. When, however, malignant segregants
      arise in the hybrid cell population, the terminal differentiation programme of
      the keratinocyte is not expressed and involucrin ceases to be made. It seemed
      possible that if the synthesis of involucrin, a critical marker of keratinocyte
      terminal differentiation, could be completely inhibited, this differentiation
      programme might be disrupted, and the malignant phenotype might then reappear in
      the non-malignant hybrids. This question was investigated further in the present
      paper. Total, and specific, inhibition of involucrin synthesis was indeed
      achieved by a sequential two-step antisense procedure, which might provide a
      systematic general method for the complete inactivation of other selected target
      genes.

PMID- 1385461
TI  - Cystic fibrosis: new perceptions, new strategies.

PMID- 1385460
TI  - Distribution of desmosomal proteins in F9 embryonal carcinoma cells and
      epithelial cell derivatives.
AB  - In diverse epithelia, cytoskeletal keratin intermediate filaments (IFs)
      associated with the cytoplasmic face of intercellular junctional desmosomes. The
      processes underlying desmosome formation and keratin IF interactions remain
      unclear. We have examined F9 embryonal carcinoma (EC) cell differentiation as a
      model for embryonic development of epithelial surface desmosomes. As determined
      by immunofluorescence microscopy and biochemical protein techniques, F9 EC cells,
      which lack surface desmosomes and keratin IFs, express the desmosomal proteins
      desmoplakins I and II (DP I/II), desmoglein I (DG I) and plakoglobin (PK). DP
      I/II are present at low level and are relatively soluble in buffer containing
      Triton X-100. Immunofluorescence localizes DP I/II to the juxtanuclear,
      centrosomal region. Species of DG I and PK are detected in both the Triton X-100
      soluble and -insoluble protein fractions. DG I appears dispersed throughout the
      cell while PK resides at cell-cell boundaries. In epithelial cell cultures
      induced by retinoic acid (RA) treatment, each of the desmosomal proteins is
      organized into punctate desmosome-like structures with the appearance of simple
      epithelial K8/K18 IFs. The steady-state levels of DP I/II and PK increase with a
      partitioning of the majority of the desmosomal components into the insoluble
      fraction. In epithelial cells which lack distinct surface desmosomes, an
      intracellular association of keratin bundles with DP I/II is observed, suggesting
      that keratin filaments may facilitate the translocation of these desmosomal
      components to the cell surface. Parietal endoderm-like cells, derived by
      treatment with RA and dibutyryl cAMP, are analogous to F9 EC cells in that the
      cells express desmosomal components and do not display surface desmosomes.
      Moreover, K8 and K18 do not form distinct filaments, and the protein and RNA
      levels of K8 are low relative to epithelial cells induced by RA alone. The F9
      system appears to be a relevant model for studies of desmosome assembly and the
      potential interactions of desmosomal proteins and keratin IFs in embryonic
      epithelial cell types.

PMID- 1385462
TI  - gamma-Aminobutyric acid, catecholamine and indoleamine determinations from the
      same brain region by high-performance liquid chromatography with electrochemical
      detection.
AB  - A new procedure for the measurement of gamma-aminobutyric acid, norepinephrine,
      dopamine, serotonin and 5-hydroxyindoleacetic acid from the same brain region was
      developed. In general, two separate high-performance liquid chromatographic runs
      were performed, one for the gamma-aminobutyric acid determination and one for the
      determination of the monoamines. The electrochemical detection of gamma
      aminobutyric acid was determined by a new procedure that utilized a small aliquot
      of the brain sample prepared for monoamine measurement. This assay was linear and
      parallel between 6 and 200 ng per 20-microliters injection with 5-aminovaleric
      acid utilized as an internal standard. Inter-assay variability averaged 5%
      throughout the assay with gamma-aminobutyric acid values in the gerbil
      hypothalamus of 344 micrograms/g. The catecholamine assay has been characterized
      previously and utilizes 3,4-dihydroxybenzylamine as an internal standard with
      less than 5% variability. Norepinephrine, dopamine, serotonin and 5
      hydroxyindoleacetic acid levels in the gerbil hypothalamus averaged 2922, 729,
      797 and 272 ng/g, respectively. This new protocol allows a wide range of
      neurochemicals to be determined and evaluated from the same brain region.

PMID- 1385463
TI  - Erythrocyte partitioning in dextran-poly(ethylene glycol) aqueous phase systems.
      Events in phase and cell separation.
AB  - Early events in the partitioning process which involve characteristic kinetics of
      cell- and phase-specific interactions and phase separation have been described
      previously. This paper reports on red cell-phase droplet interactions pertaining
      at the time of usual phase sampling (i.e., the time at which a clear bulk
      interface is first apparent) and beyond in cell partitioning and countercurrent
      distribution experiments. In non-charge-sensitive phase systems close to the
      critical point, cells can be free or attached to phase droplets. Cells that are
      free are virtually completely in the top phase, whereas different cell
      populations that show essentially complete binding to droplets can nevertheless
      have different partition ratios and be separated, thus reflecting the effects of
      the difference in the cells' avidity for the phase droplets during the early,
      elapsed events in partitioning. At higher polymer concentrations (i.e., higher
      interfacial tensions), the cell populations, completely bound to phase droplets,
      partition completely to the interface, and consequently cannot be separated. When
      such systems are made charge-sensitive by the generation of a Donnan potential
      between the phases or made into affinity systems by the incorporation of PEG
      ligands (e.g., PEG-palmitate), there is a decrease in the avidity of the cells
      for phase droplets. The resulting increase in the ratio of free to droplet-bound
      red cells in the top phase at the time of sampling correlates with an increase in
      the partition ratio, P, observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385465
TI  - PCR amplification of a specific double-stranded RNA region of Fiji disease virus
      from diseased sugarcane.
AB  - A 450-bp region from one species of the segmented dsRNA genome of Fiji disease
      virus (FDV) was amplified from total nucleic acid extracts of diseased plants by
      reverse transcription with MMLV, followed by amplification with Taq DNA
      polymerase (RT-PCR). Other FDV-specific regions (c 150 bp and c 270 bp) were also
      amplified from the dsRNA template. FDV cDNA was only synthesised when the viral
      dsRNA template was boiled and quenched with FDV-specific or random hexamer
      primers. The reverse transcriptase/DNA polymerase enzyme rTth appeared to yield
      only the 150 bp fragment from the dsRNA template under the conditions used. The
      level of sensitivity of RT-PCR for purified FDV dsRNA was 100 ag, approximately
      10(4)-fold more sensitive than detection with biotinylated DNA probe.

PMID- 1385464
TI  - A simple and rapid method of preparing large fragments of dengue virus cDNA from
      replicative-form RNA using reverse transcriptase and PCR.
AB  - A method is described for cloning large fragments (1.5 kb to 2 kb) of dengue
      virus cDNA from replicative-form viral RNA. Aedes albopictus cells (C6/36 clone)
      infected with dengue virus contain double-stranded, replicative-form RNA
      molecules which were used as a template for an initial reverse transcription
      using a primer containing sequence homologous to regions of the genome at or near
      the 3' end of the gene being studied. The product was then used as a template for
      polymerase chain reaction (PCR) amplification using the same 3' primer and a
      second which hybridized to a region at the 5' end of the sequence to be cloned.
      Both primers were engineered to contain specific restriction enzyme cutting sites
      which enabled the PCR product to be cut and cloned directly into plasmids for
      sequencing and expression studies. We have used this method to construct clones
      of the envelope glycoprotein gene (E) and the non-structural genes 1 and 2a
      (NS1/2a) and 3 (NS3) of dengue type 2, Tonga 1974 strain, and E and NS1/2a from
      dengue type 3, H-87 strain, either as discrete genes or as constructs with long
      and short leader sequences, with or without anchor sequences. The method could be
      applied to the cloning of any gene from any flavivirus, directly from infected
      cell extracts, without the necessity for tedious virus purification steps.

PMID- 1385466
TI  - Detection of tobacco rattle virus by reverse transcription and polymerase chain
      reaction.
AB  - An assay involving reverse transcription followed by polymerase chain reaction
      specifically detected tobacco rattle virus RNA in extracts of infected plants. It
      detected a wide range of serological variants and typical non-particle producing
      NM-type isolates. The sensitivity of the method was sufficient to detect TRV RNA
      in 10 ng total nucleic acid from an infected plant, or in a relatively crude
      nucleic acid preparation from 60 micrograms infected leaf tissue.

PMID- 1385467
TI  - Endocrine effects and pharmacokinetic characteristics of a potent new
      gonadotropin-releasing hormone antagonist (Ganirelix) with minimal histamine
      releasing properties: studies in postmenopausal women.
AB  - A potent and safe GnRH antagonist has been sought unsuccessfully for the last 2
      decades. The recently developed GnRH antagonist RS-26306 or Ganirelix ([N-Ac-D
      Nal(2)1,D-pClPhe2,D-Pal(3)3,D-hArg(Et2)6,L-++ +hArg(Et2)8,D-Ala10]GnRH ; Syntex
      Research, Palo Alto, CA), exhibited high antiovulatory potency and low histamine
      releasing properties in preclinical studies. Therefore, we determined the extent
      to which single sc injections of three doses of RS-26306 (1, 3, and 6 mg)
      decreased serum concentrations of LH and FSH, the free alpha-subunit of
      LH/FSH/TSH, PRL, and testosterone in five healthy postmenopausal women. We also
      examined the pharmacokinetic characteristics of RS-26306 by quantifying serum
      levels of the drug by RIA. RS-26306 rapidly suppressed serum concentrations of
      LH, FSH, and free alpha-subunit. RS-26306 (6 mg) maximally decreased serum
      concentrations (mean +/- SEM) of LH, FSH, and free alpha-subunit by 70.1 +/-
      3.6%, 42.3 +/- 2.5%, and 74.6 +/- 3.5%, respectively. RS-26306 also decreased
      serum testosterone, but not serum PRL, concentrations. RS-26306 concentrations
      reached peak serum levels at 1.2 +/- 0.3, 1.9 +/- 0.4, and 1.8 +/- 0.5 h,
      respectively, after 1-, 3-, and 6-mg sc injections. The mean serum half-life
      values based on the terminal portion of the disappearance curves were 22.8 +/-
      2.5 and 26.9 +/- 1.0 h, respectively, after 3- and 6-mg s.c. doses. No systemic
      side-effects were noted after the administration of RS-26306. Our results
      demonstrate that the GnRH antagonist RS-26306 has favorable pharmacokinetic
      characteristics and is a potent suppressor of pituitary gonadotropin secretion in
      postmenopausal women. These attributes and the lack of systemic side-effects make
      RS-26306 a promising candidate for future clinical applications.

PMID- 1385468
TI  - Steroid and peptide regulation of insulin-like growth factor-binding proteins
      secreted by human endometrial stromal cells is dependent on stromal
      differentiation.
AB  - Endometrial stromal cells undergo decidual transformation, in response to
      epidermal growth factor (EGF) and progesterone. Since insulin-like growth factors
      (IGFs) and IGF-binding proteins (IGFBPs) are believed to be involved in
      endometrial differentiation, and insulin regulates IGFBP production in a variety
      of cells, we have investigated the modulatory roles of EGF, progesterone, and
      insulin on IGFBP secretion by long term cultures of human endometrial stromal
      cells. Without insulin, the principal IGFBP secreted into conditioned medium,
      detected by Western ligand blotting, was a 28-kilodalton (kDa) IGFBP, identified
      by immunoprecipitation as IGFBP-1. This was observed only when the stromal cells
      were decidualized. With increasing insulin, IGFBP-1 decreased to undetectable
      levels. Concomitantly, IGFBP-2 increased, as did a 24-kDa IGFBP (believed to be
      IGFBP-4) and a 28-kDa IGFBP, shown to be a glycoprotein by endoglycosidase
      sensitivity (and believed to be glycosylated IGFBP-4). In the nondecidualized
      state, insulin increased the secretion of IGFBP-3, IGFBP-2, and the 24-kDa IGFBP,
      which were slightly inhibited by EGF and relatively unaffected by progesterone
      alone. In the absence of insulin, progesterone weakly stimulated IGFBP-1
      secretion, which increased markedly when the cells were decidualized by combined
      treatment with EGF and progesterone. These data show that IGFBP-3, IGFBP-2, IGFBP
      1, and presumably IGFBP-4 and its glycosylated form are differentially regulated
      by peptide and steroid hormones in endometrial stromal cells and that their
      regulation is a function of stromal differentiation.

PMID- 1385469
TI  - Characterization of the high molecular weight insulin-like growth factor complex
      in term pregnancy serum.
AB  - Insulin-like growth factors (IGFs) circulate in human adult serum predominantly
      as a high mol wt complex of 150 kilodaltons (kDa), which is made up of three
      subunits: alpha, the acid-labile subunit, a glycoprotein of around 85-100 kDa;
      beta, the acid-stable IGF-binding protein subunit, which is the 40-kDa GH
      dependent glycoprotein IGF-binding protein-3 (IGFBP-3); and gamma, the 7.5 IGF-I
      or -II peptide subunit. During human pregnancy, all three subunits are elevated
      when measured by RIA. However, recent ligand blotting studies have shown that
      IGFBP-3 is markedly reduced during pregnancy. When pregnancy serum is acidified
      and neutralized to inactivate endogenous alpha-subunit, ternary complex formation
      is normal with exogenous radiolabeled alpha-subunit, indicating functional IGFBP
      3. We have attempted to clarify the status of IGFBP-3 and the high mol wt (alpha
      beta gamma) complex in human term pregnancy serum by further analyses. Term
      pregnancy (TP) or nonpregnancy (NP) pooled sera were fractionated on a S-300
      neutral column. The high mol wt (125-150 kDa) and the low mol wt (30-40 kDa) IGF
      IGFBP complexes were identified by both RIA for IGFBP-3 and ligand blotting; each
      was pooled separately. Half of each pool was lyophilized and rechromatographed in
      acid to separate the IGF-I peptides from their IGFBPs. The IGFBP fractions were
      recovered for further studies. When the IGFBPs from the high mol wt complex were
      cross-linked to [125I]IGF-I or -II, bands of 48, 34, 26, and 21 kDa, which were
      more intense with [125I]IGF-II, were observed, and all were immunoprecipitable by
      anti-IGFBP-3 antibody. The smaller forms were elevated in TP serum. Affinity
      cross-linking analysis with [125I]alpha-subunit showed that the IGFBPs from the
      high mol wt, but not the low mol wt, complex can reform the ternary 150-kDa
      complex when cold IGF-I or IGF-II is added exogenously. A smaller 130-kDa complex
      was also present, and it was the predominant form in TP serum. Both bands were
      immunoprecipitable by anti-IGFBP-3 antibody. When purified alpha-subunit or
      fractions from neutral Sephacryl S-300 chromatography were cross-linked to
      covalent [125I]IGF-II:IGFBP-3, a specific band at 150 kDa was observed with pure
      alpha-subunit as well as with S-300 150- to 100-kDa serum fractions. These
      results suggest that 1) functional alpha-subunit is present in TP serum; 2)
      intact as well as smaller fragments of IGFBP-3 are present in the big complex of
      TP serum and are able to bind IGF and complex with alpha-subunit; and 3) IGFBP-3
      in TP serum has reduced binding to [125I]IGF-I, but not to [125I]IGF-II.

PMID- 1385470
TI  - Human luteal cells express dipeptidyl peptidase IV on the cell surface.
AB  - We previously reported that human theca interna cells and small luteal cells
      express membrane-bound aminopeptidase N, and suggested that membrane-bound
      peptidases are involved in folliculogenesis and luteal function by regulating
      extracellular peptide concentrations. In this study, we examined the expression
      of dipeptidyl peptidase IV (DPP IV), which is a membrane-bound peptidase and has
      its catalytic domain at extracellular sites, in human granulosa cells, thecal
      cells of growing, preovulatory, and atretic follicles, as well as corpora lutea.
      Indirect immunofluorescence staining of ovarian tissues with specific monoclonal
      antibodies revealed that DPP IV was present in large and small luteal cells in
      corpora lutea. DPP IV peptidase activity was also detected histochemically in
      corpora lutea. In growing, preovulatory, and atretic follicles, there was weak
      immunoreactivity and DPP IV peptidase activity on luteinized theca interna cells,
      but not on granulosa cells. The expression of DPP IV on the cell surface of large
      and small luteal cells was confirmed by indirect immunofluorescence staining of
      freshly isolated luteal cells. These results indicate that DPP IV is a useful
      surface differentiation marker of human luteal cells and suggest that peptidases
      are involved in luteal function.

PMID- 1385471
TI  - Induction of persistently demyelinated lesions in the rat following the repeated
      adoptive transfer of encephalitogenic T cells and demyelinating antibody.
AB  - A chronic relapsing model of demyelinating experimental allergic
      encephalomyelitis (EAE) was induced in Lewis rats by the repeated co-transfer of
      encephalitogenic, myelin basic protein (MBP)-specific T cells in combination with
      a demyelinating monoclonal antibody (mAb) specific for the myelin oligodendrocyte
      glycoprotein (MOG). In controls, repeated injections of 5 x 10(5) MBP-specific T
      cells at intervals of 18-21 days resulted in an increasing resistance to the
      induction of further episodes of EAE. However, intravenous injection of the mAb 4
      days after each T cell transfer overcame this 'vaccination' effect and induced
      severe clinical relapses associated with an increasing and persistent
      neurological deficit. Histological examination revealed that four cycles of
      treatment with T cells and mAb were sufficient to result in the formation of
      large plaques of demyelination in the spinal cord that failed to undergo
      significant remyelination within 60 days of the final injection of mAb. These
      lesions consisted of a matrix of astrocytic scar tissue traversed by numerous
      naked axons. These observations demonstrate that the formation of large,
      persistently, demyelinated lesions in a T cell-mediated model of EAE in the Lewis
      rat is dependent on the presence of an appropriate anti-myelin autoantibody
      response.

PMID- 1385472
TI  - Myelin gene expression during demyelination and remyelination in aggregating
      brain cell cultures.
AB  - Remyelination can be studied in aggregating rat brain cell cultures after limited
      demyelination. Demyelination was induced using a monoclonal antibody against
      myelin/oligodendrocyte glycoprotein (MOG mAb), in the presence of complement. De-
      and remyelination were assessed by measuring myelin basic protein (MBP). Two days
      after removing the MOG mAb, MBP levels reached 50% of controls and after 7 days
      93%. During this period, cell proliferation determined by [14C]thymidine
      incorporation was similar in remyelinating and control cultures. Hormones and
      growth factors were tested for possible stimulatory effect on remyelinating
      cultures. Bovine growth hormone (bGH), triiodothyronine (T3), basic fibroblast
      growth factor (bFGF) and platelet-derived growth factor (PDGF) did not improve
      remyelination. Only epidermal growth factor (EGF) increased the level of
      remyelination. PDGF increased the rate of cell proliferation in both control and
      remyelinating cultures. A significant proportion of oligodendrocytes entered the
      cell division cycle and were not available for remyelination. The results
      obtained with PDGF and FGF (inhibition) support the idea that a pool of
      progenitor cells was still present and able to proliferate and differentiate into
      myelinating oligodendrocytes. The levels of myelin protein mRNAs were
      investigated during de- and remyelination. During demyelination, myelin protein
      mRNA levels decreased to approximately 50% of control cultures and returned to
      normal during remyelination. These preliminary results indicate that normal
      levels of gene transcription are sufficient to meet the increased need for newly
      synthesized myelin proteins during remyelination.

PMID- 1385473
TI  - Repair of a myelin lesion by Schwann cells transplanted in the adult mouse spinal
      cord.
AB  - In multiple sclerosis and experimental demyelination, oligodendrocytes and
      Schwann cells are able to repair myelin lesions of the central nervous system.
      However, spontaneous myelin repair is often insufficient. Several approaches to
      enhance remyelination have been considered and transplantation of myelin-forming
      cells has been proposed as one of them. In this paper, we present results which
      confirm the ability of transplanted Schwann cells to remyelinate an induced
      demyelinated lesion of the spinal cord. Schwann cells were either purified
      Schwann cells isolated from 1-2-day-old rat sciatic nerves, or immortalized
      Schwann cells (MSC80) arising from a purified culture of 7-day-old mouse sciatic
      nerves. They were transplanted into or at a distance from a lysolecithin-induced
      lesion of the Shiverer spinal cord. Labelling of the Schwann cells with the
      fluorochrome Hoechst 33342 enabled us to trace them after transplantation in
      their host and evaluate their ability to reach and to repair the demyelinated
      lesion. Using the Hoechst-Shiverer model, we show that when transplanted in the
      lesion, cultured Schwann cells, even immortalized, are able to remyelinate such a
      lesion efficiently. In addition, when transplanted at a distance from the lesion,
      they are able to reach and repair the lesion in time frames which allow them to
      compete actively with host oligodendrocytes.

PMID- 1385474
TI  - Interleukin 4 inhibits in vitro proliferation of leukemic and normal human B cell
      precursors.
AB  - In the present study, we have investigated the effects of IL-4 on the
      proliferation and differentiation of leukemic and normal human B cell precursors
      (BCP). We have demonstrated that IL-4 significantly inhibited spontaneous
      [3H]thymidine ([3H]-TdR) incorporation by leukemic blasts from some B lineage
      acute lymphoblastic leukemia (BCP-ALL) patients (8 of 14). Furthermore, IL-4 was
      found to suppress the spontaneous and factor-dependent (IL-7 and IL-3)
      proliferation of normal BCP (CD10+ surface [s] IgM- cells) isolated from fetal
      bone marrow. Maximum growth inhibition of either leukemic or normal BCP was
      reached at low IL-4 concentrations (10 U/ml), and the effect was specifically
      neutralized by anti-IL-4 antibody. IL-4 was further found to induce the
      expression of CD20 antigen on BCP-ALL cells from a number of the cases examined
      (5 of 8), but in contrast to leukemic cells, IL-4 failed to induce CD20 antigen
      on normal BCP. Finally, IL-4 was found to induce neither the expression of
      cytoplasmic mu chain, nor the appearance of sIgM+ cells in cultures of normal or
      leukemic BCP. Our data indicate that IL-4 has the potential to inhibit cell
      proliferation in leukemic and normal human B lymphopoiesis but is unable to drive
      the transition from BCP to mature B cells.

PMID- 1385475
TI  - Epitope regions on U1 small nuclear RNA recognized by anti-U1RNA-specific
      autoantibodies.
AB  - Autoantibodies specifically directed to U1RNA were found in patients suffering
      from systemic lupus erythematosus (SLE) overlap syndromes. To obtain more insight
      in the mechanism responsible for this U1RNA-specific antibody formation and to
      use the antibodies eventually as a tool to study U1RNA-protein (U1RNP)
      interactions, the B cell epitopes on U1RNA were mapped. Using in vitro
      synthesized domains of U1RNA, the main epitope regions were found in stemloops II
      and IV. Furthermore, 3'-end or 5'-end truncation of both stemloop II and stemloop
      IV showed that the conformation of the stemloops is critical for antibody
      recognition. Mutant studies on both stemloops indicated that in the case of
      stemloop II the stem is the main antigenic region, whereas in stemloop IV, the
      loop (E-loop) is a main target. The results of this study support the idea that
      the anti-U1RNA autoantibody could be the result of a process driven by the human
      U1RNP complex itself (antigen-driven process).

PMID- 1385476
TI  - Ion channels in human erythroblasts. Modulation by erythropoietin.
AB  - To investigate the mechanism of intracellular Ca2+ ([Cai]) increase in human
      burst-forming unit-erythroid-derived erythroblasts by erythropoietin, we measured
      [Cai] with digital video imaging, cellular phosphoinositides with high
      performance liquid chromatography, and plasma membrane potential and currents
      with whole cell patch clamp. Chelation of extracellular free Ca2+ abolished [Cai]
      increase induced by erythropoietin. In addition, the levels of inositol-1,4,5
      trisphosphate did not increase in erythropoietin-treated erythroblasts. These
      results indicate that in erythropoietin-stimulated cells, Ca2+ influx rather than
      intracellular Ca2+ mobilization was responsible for [Cai] rise. Both Ni2+ and
      moderately high doses of nifedipine blocked [Cai] increase, suggesting
      involvement of ion channels. Resting membrane potential in human erythroblasts
      was -10.9 +/- 1.0 mV and was not affected by erythropoietin, suggesting
      erythropoietin modulated a voltage-independent ion channel permeable to Ca2+. No
      voltage-dependent ion channel but a Ca(2+)-activated K+ channel was detected in
      human erythroblasts. The magnitude of erythropoietin-induced [Cai] increase,
      however, was insufficient to open Ca(2+)-activated K+ channels. Our data suggest
      erythropoietin modulated a voltage-independent ion channel permeable to Ca2+,
      resulting in sustained increases in [Cai].

PMID- 1385477
TI  - Structure-function relationships of interleukin-3. An analysis based on the
      function and binding characteristics of a series of interspecies chimera of
      gibbon and murine interleukin-3.
AB  - IL-3 is a glycoprotein cytokine involved in the hematopoietic response to
      infectious, immunologic, and inflammatory stimuli. In addition, clinical
      administration of recombinant IL-3 augments recovery in states of natural and
      treatment-related marrow failure. IL-3 acts by binding to high affinity cell
      surface receptors present on hematopoietic cells. To determine the site(s) at
      which IL-3 binds to it receptor, we analyzed a series of interspecies chimera of
      the growth factor for species-specific receptor binding and biological activity.
      The results suggest that IL-3 binds to its receptor and triggers a proliferative
      stimulus through two noncontiguous helical domains located near the amino
      terminus and the carboxy terminus of the molecule. To corroborate these findings,
      we have also mapped the binding epitopes of 10 mAb of human or murine IL-3, and
      have defined four distinct epitopes. Two of these epitopes comprise the amino
      terminal receptor binding domain. A third epitope corresponds to the carboxy
      terminal receptor interactive domain, and the fourth epitope, apparently not
      involved in the interaction of IL-3 and its receptor, lies between these sites.
      And on the basis of sandwich immunoassays using pairs of these mAbs, the two
      receptor interactive regions appear to reside in close juxtaposition in the
      tertiary structure of the molecule. These results provide a correlation of the
      structure-function relationships of IL-3 that should prove useful in evaluating
      the details of IL-3-IL-3 receptor interaction and in the rational design of
      clinically useful derivatives of this growth factor.

PMID- 1385478
TI  - Macrophages, T cell receptor usage, and endothelial cell activation in the
      pancreas at the onset of insulin-dependent diabetes mellitus.
AB  - Current knowledge of the phenotype of mononuclear cells accumulating in
      pancreatic islets in insulin-dependent diabetes (IDDM) and factors determining
      their homing into the pancreas is limited. Therefore, a pancreas obtained at the
      onset of IDDM was studied in detail. Cryostat sections were stained for
      mononuclear cell types, T cell receptor subtypes, and adhesion molecules of
      vascular endothelium and studied by immunofluorescence microscopy, and peripheral
      blood mononuclear cells were phenotyped using flow cytometry.
      Monocytes/macrophages (lysozyme- or CD 14-reactive cells) were identified among
      other mononuclear cell types in islet infiltrates. V beta 8-positive T cells were
      overrepresented, but T cells with other V beta s studied (V beta 5, V beta 5.1, V
      beta 6, V beta 12) were also found. The vascular endothelium of the islets and
      many small vessels nearby islets strongly expressed intercellular adhesion
      molecule-1, whereas vascular cell adhesion molecule-1 and E-selectin were totally
      absent. We conclude: (a) that increased expression of intercellular adhesion
      molecule-1 on vascular endothelium may increase endothelial adhesion of
      mononuclear cells and enhance their accumulation in the pancreas during diabetic
      insulitis; (b) that T cells with certain T cell receptors can be enriched in
      infiltrated pancreatic islets; and (c) that macrophages and antigen-specific CD 8
      positive T cells are involved in pancreatic beta cell destruction at the onset of
      IDDM.

PMID- 1385479
TI  - Expression and localization of proteins of the complement system in human skin.
AB  - The complement system participates in the immune recognition of foreign antigens,
      many of which may penetrate the skin by physical injury or transcutaneous
      adsorption. In this study, we examined the presence of complement components and
      complement regulatory proteins in the human skin and cultured human
      keratinocytes. Immunofluorescence studies showed C3, Factor B, decay accelerating
      factor, the C3b receptor (CR1), and C3d receptor (CR2), distributed among cells
      of the epidermis as well as on cultured keratinocytes. Immunoblot analysis of
      keratinocytes supernatants showed the presence of C3 with a molecular weight of
      approximately 180 kD. The decay accelerating factor was localized as previously
      reported on elastic fibers; additionally it was observed in the basement membrane
      zone. In situ hybridization studies suggest the expression of CR1 and CR2 mRNA in
      human epidermis. These results show the presence in the human epidermis of
      complement components that are capable of generating the initial C3 convertase of
      the alternative pathway. The presence of complement regulatory proteins could
      endow keratinocytes with immune functions such as the regulation of complement
      activation and endocytosis of C3 opsonized particles.

PMID- 1385481
TI  - Immunochemical characterisation of a murine monoclonal anti-idiotypic antibody.
AB  - Y7, a murine monoclonal IgG1 kappa antibody against a human monoclonal IgM lambda
      DJ molecule, was affinity purified on an IgM lambda immunoaffinity column. As
      detected by enzyme-linked immunosorbent assay (ELISA) the isolated Y7 monoclonal
      antibody was shown to be not cross-reactive with human IgG, human secretory IgA,
      mu chain, lambda + kappa chains and another human monoclonal IgM lambda BR.
      Binding to the polyclonal human IgM standard in the same assay was about 30
      percent. The epitope specificity of affinity purified and biotinylated Y7 MoAb
      was localized only in the nonreduced pepsin Fab fragments of IgM lambda DJ
      immunogen. As the immunogen was determined to be a specific antibody to
      phosphorylcholine, the specificity of Y7 MoAb was further ascertained in its
      capacity to induce 95% inhibition of immunogen binding for phosphorylcholine.

PMID- 1385480
TI  - Molecular cloning and characterization of the constitutive bovine aortic
      endothelial cell nitric oxide synthase.
AB  - The constitutive endothelial cell nitric oxide synthase (NOS) importantly
      regulates vascular homeostasis. To gain understanding of this enzyme, a pEF BOS
      cDNA library of 5 x 10(5) clones was prepared from bovine aortic endothelial
      cells (BAEC) and screened with a 2.8-kb cDNA BamHI fragment of rat brain NOS.
      Clone pBOS13 was found to express NO synthase activity when transfected into COS
      7 cells. Sequence analysis revealed sequences compatible with binding domains for
      calcium/calmodulin, flavin mononucleotide, flavin adenine nucleotide and NADPH.
      The deduced amino acid sequence revealed a protein with a relative mol mass of
      133,286, which is 58% homologous to the rat cerebellar NOS and 51% homologous to
      the mouse macrophage NOS. The amino-terminal portion of the protein exhibits
      several characteristics peculiar to the endothelial cell NOS. These include a
      proline-rich region and several potential sites for proline-directed
      phosphorylation as well as a potential substrate site for acyl transferase.
      Northern hybridization to mRNA from cultured BAEC revealed an abundant 4.8-kb
      message, which was not increased by coincubation with tumor necrosis factor
      alpha, but was markedly increased by exposure to shear stress for 24 h. The
      unique features of the endothelial cell NO synthase, particularly in the amino
      terminal portion of the molecule, may provide for novel regulatory influences of
      enzyme activity and localization.

PMID- 1385483
TI  - Subclinical ischaemic episodes during the steady state of sickle cell anaemia.
AB  - AIMS: To determine the clinical, haematological, biochemical and rheological
      changes that occur in the asymptomatic steady state of sickle cell anaemia.
      METHODS: Patient self-assessment visual analogue scores (for wellbeing and
      tiredness), the blood concentration of acute phase proteins (C-reactive protein,
      orosomucoid, and fibrinogen), and blood rheology (percentage of dense cells and
      the number of sickled cells that occluded pores 5 microns in diameter) were
      studied longitudinally on 10 occasions in each of 20 outpatients with sickle cell
      anaemia. RESULTS: Patients in the steady state showed fluctuation in visual
      analogue scores, in concentration of acute phase proteins, and in rheological
      parameters consistent with minor episodes of tissue injury. Significantly more
      variation in acute phase proteins occurred in the steady state of 14 of the 20
      patients who developed one or more vaso-occlusive crises during the 16 month
      study period. Rheological fluctuation in the steady state simulated rheological
      change during crisis, namely a transient rise and then fall in the number of
      dense and poorly filterable cells. CONCLUSIONS: The term "steady state" is a
      misnomer, being characterised by biochemical and rheological fluctuation
      consistent with minor episodes of microvascular occlusion that are insufficient
      to cause the overt tissue infarction of painful crisis.

PMID- 1385482
TI  - Amyloid in prostatic corpora amylacea.
AB  - AIM: To determine the presence and nature of amyloid in prostatic corpora
      amylacea using immunohistological studies. METHODS: Prostatic tissue from 18
      transurethral and two open resection specimens was studied. Paraffin wax embedded
      tissue sections were stained with haematoxylin and eosin and the alkaline Congo
      red method with and without previous treatment with potassium permanganate.
      Sections were also stained with antibodies to amyloid A, beta 2 microglobulin,
      lambda and kappa light chains, prealbumin IgA, G, M, S100 protein, prostatic
      specific antigen, amyloid P component and CAM 5.2 (control and blocking studies
      were performed). RESULTS: The prostatic corpora amylacea universally showed the
      presence of amyloid. In all instances this contained beta 2 microglobulin.
      CONCLUSION: Prostatic corpora amylacea represents a localised amyloidosis of beta
      2 microglobulin origin that is unrelated to chronic renal failure and
      haemodialysis.

PMID- 1385484
TI  - Specificity of colon specific antigen and colon ovarian tumour antigen.
AB  - Sections (5 microns thick) from 101 primary adenocarcinomas (including ovarian,
      colorectal, gastric, breast, oesophageal, prostatic, pancreatic, endometrial and
      gall bladder) were incubated wtih anticolon specific antigen (CSA) and anticolon
      ovarian tumour antigen (COTA) antibodies using the peroxidase antiperoxidase
      technique with positive and negative controls. Anti-CSA positivity was seen in 19
      of 20 colonic adenocarcinomas, but it was also seen in a large number of the
      other tumours. While anti-COTA staining was positive in 16 of 20 colonic
      adenocarcinomas and 20 of 30 ovarian adenocarcinomas, it was also positive in a
      large number of the tumours. Anti-CSA and anti-COTA are not adequately specific
      in the identification of a colonic or ovarian origin of an adenocarcinoma and
      cannot reliably be applied to the identification of a metastatic adenocarcinoma
      of unknown primary site.

PMID- 1385485
TI  - Effect of Tisseel on healing after periodontal flap surgery.
AB  - The purpose of this investigation was to evaluate the effect on healing of fast
      and slow absorbable Tisseel in combination with periodontal flap surgery.
      Mucoperiosteal flaps were raised on the buccal aspect of maxillary premolars and
      mandibular premolars and first molars in 4 beagle dogs. The underlying buccal,
      interproximal and inter-radicular bone was then removed to a level of
      approximately 5 mm apically to the original bone crest and half way into the
      interdental spaces and bifurcations. The exposed root surfaces were curetted in
      order to remove the periodontal ligament tissue, and a notch was made in the root
      surface at the base of the defects. On the control teeth, the flaps were sutured
      immediately after creation of the defects, while on the test teeth, a layer of
      fast (group I) or slow (group II) absorbable Tisseel was applied between the
      curetted roots and the subsurface of the flaps prior to suturing.
      Postoperatively, the teeth were brushed 2 x weekly. The dogs were sacrificed
      after 4 months. Histological analysis revealed that the amounts of new attachment
      and bone regrowth were similar in the test and control groups, although the
      results tended to be most favorable for the group of teeth treated with fast
      absorbable Tisseel (Group I).

PMID- 1385486
TI  - Substance P-containing pyramidal neurons in the cat somatic sensory cortex.
AB  - Light and electron microscopic immunocytochemical methods were used to verify the
      possibility that neocortical pyramidal neurons in the first somatic sensory
      cortex of cats contain substance P. At the light microscopic level, substance P
      positive neurons accounted for about 3% of all cortical neurons, and the vast
      majority were nonpyramidal cells. However, 10% of substance P-positive neurons
      had a large conical cell body, a prominent apical dendrite directed toward the
      pia, and basal dendrites, thus suggesting they are pyramidal neurons. These
      neurons were in layers III and V. At the electron microscopic level, the majority
      of immunoreactive axon terminals formed symmetric synapses, but some substance P
      positive axon terminals made asymmetric synapses. Labelled dendritic spines were
      also present. Combined retrograde transport-immunocytochemical experiments were
      also carried out to study whether substance P-positive neurons are projection
      neurons. Colloidal gold-labelled wheat germ agglutinin conjugated to
      enzymatically inactive horseradish peroxidase was injected either in the first
      somatic sensory cortex or in the dorsal column nuclei. In the somatic sensory
      cortex contralateral to the injection sites, a few substance P-positive neurons
      in layers III and V also contained black granules, indicative of retrograde
      transport. This indicates that some substance P-positive neurons project to
      cortical and subcortical targets. We have therefore identified a subpopulation of
      substance P-positive neurons that have most of the features of pyramidal neurons,
      are the probable source of immunoreactive axon terminals forming asymmetric
      synapses on dendritic spines, and project to the contralateral somatic sensory
      cortex and dorsal column nuclei. These characteristics fulfill the criteria
      required for classifying a cortical neuron as pyramidal.

PMID- 1385487
TI  - Raphespinal and reticulospinal axon collaterals to the hypoglossal nucleus in the
      rat.
AB  - Neurons in the medial tegmental field project directly to spinal somatic
      motoneurons and to cranial motoneuron pools such as the hypoglossal nucleus. The
      axons of these neurons may be highly collateralized, projecting to multiple
      levels of the spinal cord and to many diverse regions at different levels of the
      neuraxis. We employed a double fluorescent retrograde tracer technique to examine
      whether medial tegmental neurons that project to the spinal cord also project to
      the hypoglossal nucleus. Injections of Diamidino Yellow into the hypoglossal
      nucleus and Fast Blue into the spinal cord produced large numbers of double
      labeled neurons in the medial tegmental field, particularly in the caudal raphe
      nuclei and adjacent ventromedial reticular formation. In these structures the
      number of neurons projecting to both the hypoglossal nucleus and the spinal cord
      was equivalent to the number of neurons projecting to multiple levels of the
      spinal cord observed in control animals. Fewer neurons projecting to both the
      hypoglossal nucleus and the spinal cord were observed in several other nuclei and
      subregions of the medial tegmental field, while almost no such neurons were
      observed in the lateral tegmental field or other pontomedullary structures. These
      results demonstrate that neurons of the caudal raphe nuclei and adjacent
      ventromedial reticular formation project to both the spinal cord and the
      hypoglossal nucleus, and support the concept that the diffuse projections to
      motoneuron pools from the medial tegmental field globally modulate both spinal
      and cranial somatic motoneuron excitability.

PMID- 1385488
TI  - Morphology of identified preganglionic neurons in the dorsal motor nucleus of the
      vagus.
AB  - To determine the degree of variation of neuronal morphology both within and
      between the subnuclei of the dorsal motor nucleus of the vagus (dmnX), structural
      features of the preganglionic neurons of each of the five primary subnuclei in
      the rat dmnX were characterized quantitatively. Each of the columnar subnuclei
      was separately labeled by application of the retrograde tracer fast blue to its
      corresponding subdiaphragmatic vagal branch. Fixed brain slices of 100 microns
      thickness were then prepared in coronal, sagittal, and horizontal orientations.
      Next, randomly selected fast blue labeled neurons (n = 1,256) were injected with
      Lucifer yellow, drawn with camera lucida, and digitized. For each cell, three
      features of the perikaryon and twelve of the dendritic tree were measured. Dorsal
      motor nucleus neurons with up to eight primary dendrites, 30 dendritic segments,
      and seventh order dendritic branches were observed. Throughout the dmnX, the
      dendrites of preganglionic neurons were preferentially oriented in the horizontal
      plane. Consistent with an organizing role for the columnar subnuclei, most
      dendrites remained within their column of origin. However, between 5 and 30% of
      the neurons in each of the columns projected dendrites into adjacent dmnX
      subnuclei or other brainstem nuclei, including the nucleus of the solitary tract
      (NTS). The cyto- and dendroarchitectural analyses revealed systematic gradations
      in morphology, although they did not support the idea that the dmnX was composed
      of multiple distinct preganglionic types. The most parsimonious interpretation of
      the data is that dmnX motorneurons are variants of a single prototype, with
      dendrites varying widely in length and degree of ramification. The extent of an
      individual preganglionic neuron's dendritic field was predicted by three factors:
      the cell's rostrocaudal position within the dmnX, its location within a
      transverse plane (i.e., its coronal position within or ectopic to the dmnX), and
      its subnucleus of origin. Neurons at rostral and midlongitudinal levels of each
      column had more extensive dendritic arbors than those at caudal levels. Ectopic
      neurons had more extensive dendritic fields than similar cells in the
      corresponding columns; in fact, of all vagal preganglionic neurons, ectopics had
      the most extensive dendritic fields. Somata and dendrites of celiac column
      neurons were more extensive than those of hepatic and gastric column cells. These
      differential regional distributions of vagal preganglionics suggest that their
      structure and function are correlated.

PMID- 1385489
TI  - Lamina I spinocervical tract terminations in the medial part of the lateral
      cervical nucleus in the cat.
AB  - The terminations of spinocervical tract fibers in the lateral cervical nucleus
      (LCN) of the cat were examined with anterogradely transported Phaseolus vulgaris
      leucoagglutinin (PHA-L) in order to analyze their organization relative to the
      most medial part and the main body (the lateral two-thirds) of the LCN, which
      have differential projections and physiological characteristics. Iontophoretic
      injections of PHA-L in laminae I-V of the spinal dorsal horn yielded dense
      labeling in somatotopically appropriate regions of the main body of the LCN, and,
      as seen previously with horseradish peroxidase, additional terminations were
      present in the medial LCN after injections at either cervical or lumbar spinal
      levels. The morphological characteristics of the PHA-L labeling in these two
      parts of the LCN were different. Terminations in the lateral LCN consisted of
      dense clusters of thick fibers bearing large numbers of boutons. The terminal
      axons in the medial part of the LCN displayed a reticulated network of
      longitudinally oriented, fine fibers with well-spaced varicosities. Some of the
      fine fibers in the medial LCN appeared to be collaterals of thicker fibers that
      terminated in the lateral LCN. Injections of PHA-L that were restricted to lamina
      I resulted in terminal labeling only in the medial LCN. The labeling was more
      sparse than that observed in the medial LCN after larger dorsal horn injections
      but displayed the same morphological characteristics. Lamina I terminations were
      seen in the medial LCN after cervical or lumbar injections on both the
      ipsilateral and contralateral sides. The PHA-L observations were corroborated by
      the presence of many retrogradely labeled lamina I cells at both cervical and
      lumbar spinal levels, following injections of cholera toxin subunit b or
      rhodamine-labeled microspheres in the medial LCN. In addition, double
      immunofluorescent labeling for PHA-L and substance P was performed in a few
      cases, since substance P immunoreactivity is present in fibers in the medial LCN
      and also in cell bodies in lamina I; however, very few spinocervical fibers
      displayed immunoreactivity for both antigens. These observations indicate that
      the medial part of the LCN receives input from lamina I neurons, and probably
      from lamina III-V neurons as well, at cervical and lumbar spinal levels. The
      lamina I input to the medial LCN provides a basis for the small population of
      nociceptive neurons that differentiate the medial LCN. The lamina I input could
      also be responsible for the general inhibition of lateral LCN neurons by wide
      field noxious stimulation, via activation of GABAergic interneurons in the medial
      LCN.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1385491
TI  - Topographic organization of subcortical projections to the anterior thalamic
      nuclei in the rat.
AB  - Subcortical projections to the anterior thalamic nuclei were studied in the rat,
      with special reference to projections from the mammillary nuclei, by retrograde
      and anterograde transport of wheat germ agglutinin conjugated to horseradish
      peroxidase. The medial mammillary nucleus (MM) projects predominantly
      ipsilaterally to the entire anterior thalamic nuclei, whereas the lateral
      mammillary nucleus projects bilaterally to the anterodorsal nucleus (AD) of the
      anterior thalamic nuclei. A topographic relationship was recognized between the
      MM and the anterior thalamic nuclei. The dorsal region of the pars mediana of the
      MM projects to the interanteromedial nucleus (IAM), whereas the ventral region
      projects to the rostral part of the anteromedial nucleus (AM). The dorsal and the
      ventral regions of the pars medialis project to the dorsomedial part of the AM at
      its caudal and rostral levels, respectively. The dorsomedial region of the pars
      lateralis projects to the ventral AM. The ventrolateral region of the pars
      lateralis projects to the ventral part of the anteroventral nucleus (AV) in such
      a manner that rostral cells project rostrally and caudal cells project caudally.
      The pars basalis projects predominantly ipsilaterally to the dorsolateral AV and
      bilaterally to the AD. The rostrolateral region of the pars posterior projects to
      the lateral AV, whereas the medial and the caudal regions of the pars posterior
      project to the dorsomedial AV. The rostrodorsal part of the nucleus reticularis
      thalami was found to project to the anterior thalamic nuclei; cells located
      rostrally in this part project to the IAM and AM, whereas cells located
      caudodorsally project to the AV and AD. The laterodorsal tegmental nucleus
      projects predominantly ipsilaterally to the AV, especially to its dorsolateral
      part. The present study demonstrates that subdivisions of the subcortical
      structures are connected to the subnuclei of the anterior thalamic nuclei, with a
      clear-cut topography arranged in the dorsoventral and the rostrocaudal
      dimensions.

PMID- 1385490
TI  - Multiple neurotransmitters in the tuberomammillary nucleus: comparison of rat,
      mouse, and guinea pig.
AB  - Tuberomammillary neurons in the posterior hypothalamus are the sole source of
      neuronal histamine in adult mammalian brain. In the rat, these cells are reported
      to contain immunoreactivity for gamma-aminobutyric acid (GABA) and several
      neuropeptides. We compared the presence of these substances in the
      tuberomammillary cells of the rat, mouse, and guinea pig. In all three species,
      all histamine-immunoreactive neuronal cell bodies were positive for GABA. This
      suggests that GABAergic transmission may be important in tuberomammillary
      function. No cell bodies immunoreactive for thyrotropin releasing hormone (TRH)
      were found in the guinea pig or mouse tuberomammillary area. In contrast, about
      14% of the histamine-immunoreactive tuberomammillary cells in the rat were TRH
      positive. These cells were small or medium-sized and were located only in the
      medial part of the tuberomammillary complex. An antibody against porcine galanin
      stained about 45% of the tuberomammillary cell bodies in the rat and about 28% in
      the mouse, but none in the guinea pig. A large proportion of the cells in the rat
      and mouse, but none in the guinea pig, were positive for met-enkephalin-arg-phe.
      In contrast, all histamine-containing tuberomammillary cells in the guinea pig,
      but none in the rat or mouse, were immunoreactive for met-enkephalin. This may
      indicate a different expression of proenkephalin-derived peptides in the
      tuberomammillary neurons in these species. Some substance P-immunoreactive cell
      bodies were located in the tuberomammillary area in all three species. However,
      only 3% of the histamine-immunoreactive cell bodies in the rat and mouse but none
      in the guinea pig were substance P-positive. The neurochemical properties of the
      tuberomammillary nucleus that exhibited species commonality deserve to be studied
      neurochemically and electrophysiologically in order to determine the functional
      relevance of coexisting transmitters in this nucleus.

PMID- 1385492
TI  - Nerve growth factor receptor-immunoreactive neurons within the developing human
      cortex.
AB  - A monoclonal antibody recognizing the p75 receptor for nerve growth factor (NGF)
      was used to assess the immunohistochemical expression of NGF receptors within the
      developing human neo-, limbic, and paralimbic cortices as well as the hippocampal
      complex. Between embryonic weeks 16 and 26, a transient population of neurons
      located within the upper and lower subplate zones of the neo-, limbic, and
      paralimbic cortices expressed the receptor for NGF. In contrast, NGF receptor
      immunoreactive neurons were only observed in the upper subplate zone of the
      entorhinal cortex at embryonic week 40 (term), a staining pattern not observed in
      a 5-year-old specimen. The expression of NGF receptor-immunoreactive neurons
      within the upper subplate zone between embryonic weeks 16 and 40 was
      characterized by a dense band of immunoreactive neurons and neuropil. These
      neurons were bipolar with basal and apically directed neurites. NGF receptor
      immunoreactive neurons were also scattered throughout the lower subplate zone and
      underlying white matter between embryonic weeks 19 and 26. These neurons were
      multipolar, with less apically directed neurites. NGF receptor-immunoreactive
      subplate neurons displayed a topographic distribution with the heaviest
      concentration found within limbic and paralimbic cortices as well as association
      neocortex. In contrast, light to moderate NGF receptor-immunoreactivity was seen
      in sensory-motor cortex. Within the hippocampal complex, only a few lightly
      stained NGF receptor-immunoreactive neurons were seen within the fimbria, hilar
      region of the dentate gyrus, and subiculum. The expression of NGF receptor
      immunoreactivity increased within the subplate zone of the pre- and parasubiculum
      culminating in intense entorhinal cortex staining. As the entorhinal cortex
      merged with the developing inferior temporal association cortex, there was a
      marked reduction in staining intensity. In contrast to those in the subplate
      zone, neurons within the germinal zone and cortical plate were NGF receptor
      immunonegative at all times examined. The presence of NGF receptors in the
      subplate zone suggests that neurotrophins such as NGF play an important role in
      the transient viability of these neurons as well as in the guidance of cortical
      afferent inputs into topographically organized regions of the cerebral cortex.

PMID- 1385493
TI  - The structure of the diencephalic prepacemaker nucleus revisited: light
      microscopic and ultrastructural studies.
AB  - The prepacemaker nucleus (PPn), a bilateral cluster of neurons at the boundary of
      diencephalon and mesencephalon, controls frequency modulations of the electric
      organ discharge in weakly electric knifefish (Eigenmannia sp.). Previous light
      microscopic studies employing retrograde labelling with horseradish peroxidase
      suggested that the PPn is restricted to a small area, located approximately 400
      microns laterally from the third ventricle and fusing at its medial edge with the
      thalamic central posterior nucleus (CP). In the present investigation we used
      Phaseolus vulgaris-leucoagglutinin and cholera toxin as highly sensitive markers.
      In contrast to the previous studies, these experiments yielded a large number of
      labelled cells not only in the region of the traditionally defined PPn but also
      in an area reaching far into the CP. Since the PPn has been defined by retrograde
      labelling rather than by topographic criteria, this result questions the
      traditional separation between PPn and CP. Such a notion is in agreement with
      observations of Nissl-stained sections at the light microscopic level and with a
      quantitative analysis of several morphological characteristics of the cell bodies
      in the PPn and CP at the ultrastructural level. Both sets of experiments failed
      to find differences between the two nuclei. Furthermore, autoradiographic studies
      have shown that, even in adulthood, cells are continuously born within the
      ventricular zone of the CP, and at least some of these newborn cells
      differentiate into CP cells and migrate laterally towards the PPn. Therefore, we
      postulate that CP and PPn form one large complex, with the medial CP providing
      precursors of neurons in the lateral CP and PPn.

PMID- 1385494
TI  - A multiterminal stretch receptor, chordotonal organ, and hair plate at the wing
      hinge of Manduca sexta: unravelling the mystery of the noctuid moth ear B cell.
AB  - The present study aims to shed light on the evolutionary origin of the B cell, a
      sensory element of unknown function in the noctuid moth ear. Peripheral
      projections of the metathoracic nerve IIIN1b1, homologue of the noctuid moth
      tympanic nerve, are described in the atympanate moth Manduca sexta on the basis
      of dissections with the aid of Janus Green B, and intracellular tracer dyes
      Lucifer yellow and cobalt lysine. A large multiterminal (Type II) neurone,
      attaching to membranous cuticle ventral to the hind wing axillary cord, was
      discovered. This cell appears to be homologous to the B cell in the noctuid moth
      ear. Recordings from the IIIN1b1 nerve in M. sexta reveal a continuous train of
      large, uniform spikes, presumed to originate from the multiterminal cell. This
      unit increases its rate of firing in response to hind wing elevation, suggesting
      that it functions as a stretch receptor monitoring wing movements during flight.
      Also identified in the tympanic nerve homologue, and closely associated with the
      multiterminal cell, were a chordotonal organ and hair plate. The chordotonal
      organ consists of a proximal scolopidial region and a distal strand that attaches
      to the sclerotized epimeron slightly medial to the multiterminal cell. This
      simple chordotonal organ, having three uniterminal (Type I) sensory cells, is
      homologous to the auditory cells of the noctuid moth ear. The significance of
      these receptors as proprioceptors in M. sexta, and as evolutionary precursors to
      the noctuid moth ear, is discussed.

PMID- 1385496
TI  - Topography of ganglion cells in the dog and wolf retina.
AB  - The topographical distribution of retinal ganglion cells in seven breeds of dog
      (Canis lupus f. familiaris) and in the wolf (Canis lupus) was studied in retinal
      wholemounts stained with cresyl violet or with a reduced silver method. A
      prominent feature of all wolf retinae was a pronounced "visual streak" of high
      ganglion cell density, extending from the central area far into both temporal and
      nasal retina. By contrast, either a pronounced or a moderate visual streak was
      found in dog retinae. It is hypothesized that a pronounced streak is an
      archetypal feature of Canis lupus, and that the moderate streak in some dogs is a
      corollary of breeding during domestication. Irrespective of the differences in
      streak form and retinal area, the estimated total number of ganglion cells was
      about 200,000 cells in the wolf and 115,000 in the dog. Ganglion cell density
      maxima in the central area of the wolf were about 12,000-14,000/mm2, and in the
      dog they ranged from 6,400/mm2 to 14,400/mm2. This implies individual differences
      in visual acuity. Alpha ganglion cells constituted 3-14% of all ganglion cells in
      the dog and 1-18% in the wolf, depending on retinal location. A distinct feature
      of all dogs and wolves was the absence of alpha cells in a substantial region of
      temporal peripheral retina. This has not been found in any other mammalian
      species and suggests corresponding functional deficits.

PMID- 1385495
TI  - Immunocytochemical survey of putative neurotransmitters in taste buds from
      Necturus maculosus.
AB  - To investigate synaptic mechanisms in taste buds and collect information about
      synaptic transmission in these sensory organs, we have examined taste buds of the
      mudpuppy, Necturus maculosus for the presence of neurotransmitters and
      neuromodulators. Immunocytochemical staining at the light microscopic level
      revealed the presence of serotonin-like and cholecystokinin-like (CCK)
      immunoreactivity in basal cells in the taste bud. Nerve fibers innervating taste
      buds were immunoreactive for vasoactive intestinal peptide-like (VIP), substance
      P-like, and calcitonin gene-related peptide-like (CGRP) or compounds closely
      related to these substances. Immunoreactivity for tyrosine hydroxylase (TH) and
      choline acetyltransferase (ChAT) in the taste cells and nerve fibers was absent.
      These data suggest that serotonin, CCK, VIP, substance P, and CGRP are involved
      in synaptic transmission or neuromodulation in the peripheral organs of taste. No
      evidence was found for cholinergic or adrenergic mechanisms on the basis of the
      absence of immunocytochemical staining for key enzymes involved in these two
      transmitter systems.

PMID- 1385497
TI  - Pathological changes in the reproductive tract of male rhesus monkeys associated
      with age and simian AIDS.
AB  - The pathological changes associated with ageing and simian immunodeficiency virus
      (SIV) infection in groups of immature, adult and ageing Rhesus monkeys were
      studied. Eighty three per cent (5 of 6) of uninfected ageing animals had
      hyperplasia of the prostate, 33 per cent (2 of 6) had mild prostatitis and in 66
      per cent (4 of 6) there were calcified concretions in the seminal vesicles. The
      testes were normal and showed active spermatogenesis. In the SIV-infected
      animals, two types of lesion occurred; the most common, in 81 per cent (18 of 22
      monkeys), was the presence of focal lymphoid infiltrations in the epididymis,
      prostate or seminal vesicles. The other was hypospermatogenesis (23 per cent, 4
      of 17) with degeneration of seminiferous tubules. Immunocytochemical staining
      demonstrated that the lymphoid masses contained approximately equal numbers of B
      and T lymphocytes, but the majority of diffusely scattered cells were T
      lymphocytes. Staining for SIV antigen identified small numbers of positive
      lymphocytes and macrophages in all tissues.

PMID- 1385498
TI  - MRI of temporal lobe pleomorphic xanthoastrocytoma.
AB  - Pleomorphic xanthoastrocytomas (PXA) are classically supratentorial, peripherally
      located, well-circumscribed, partially cystic neoplasms, which can enhance on CT
      following the administration of intravenous contrast agents. Focal calcification
      may also be seen. Although the CT appearance has been described, we report the MR
      findings in two cases of histologically documented temporal lobe PXA. The two
      well-circumscribed lesions were predominantly cystic and both contained a Gd-DTPA
      enhancing mural nodule. The latter was isointense with gray matter on T1-weighted
      images and hyperintense on T2-weighted scans. Minimal surrounding edema was
      present. Histologically, PXA may be confused with glioblastoma multiforme (GBM)
      due to the pronounced cellular pleomorphism. Because of their potentially more
      indolent behavior compared with GBM, it is important to recognize the gross
      morphologic characteristics of this rare tumor on MR. The MR pattern of a cystic
      lesion with enhancing mural nodule is characteristic of PXA, but not diagnostic,
      and other lower grade gliomas such as ganglioglioma and pilocytic astrocytoma
      need to be considered. The MR and CT appearance of PXA can provide critical
      information for the pathologist, especially when only a small amount of tissue is
      obtained for histologic evaluation.

PMID- 1385499
TI  - Accuracy of in-vivo assessment of prostatic volume by MRI and transrectal
      ultrasonography.
AB  - More accurate noninvasive estimation of prostate size is important in therapeutic
      trials for benign prostatic hyperplasia. The accuracy of MRI and transrectal
      ultrasound (TRUS) in assessing prostate weight was evaluated in 48 patients who
      underwent radical prostatectomy for stage A or B cancer. The volume derived from
      the wet weight of the freshly excised specimen was used as a reference. We
      compared that volume with volume estimates derived from the three-axis linear
      dimension measurement by MRI and TRUS using a tissue density of 1.05 g/cc and the
      standard formula for an ellipsoid object. Prostate and seminal vesicle volumes
      were also computed by contouring T2-weighted 5 mm thick contiguous MR images
      using a semiautomatic edge detection program and pixel summation. Three-axis
      volume MRI method versus volume from wet weight has slightly less scatter than
      TRUS three-axis method (r = 0.85 vs r = 0.81). Contoured MR volume method has the
      least scatter r = 0.93, statistically better than the linear axis method.
      Contoured MRI volumetric analysis appears superior to linear MRI or TRUS methods
      in estimating true prostate volume.

PMID- 1385500
TI  - Marjolin's ulcer: immunohistochemical study of 17 cases and comparison with
      common squamous cell carcinoma and basal cell carcinoma.
AB  - Formalin-fixed, paraffin-embedded biopsy specimens of 17 cases of squamous cell
      carcinoma of Marjolin's ulcer (SCC-MU), 6 cases of common SCC (SCC), and 5 cases
      of basal cell carcinoma (BCC) were stained with three monoclonal antikeratin
      antibodies (CAM 5.2, MAK-6, and MA-903), a monoclonal antivimentin antibody (V9),
      and a polyclonal anticarcinoembryonic antigen antiserum (A115). Neoplastic cells
      of SCC-MU, SCC, and BCC showed consistently negative staining for CAM 5.2. A wide
      range of reactivity, from negative to diffuse strong positivity, among neoplastic
      cells of SCC-MU and SCC was noted with MAK-6. Alternatively, neoplastic cells of
      SCC-MU, SCC, and BCC consistently showed diffuse moderate to strong reactivity
      with MA-903. These findings imply that SCC-MU has largely high-molecular-weight
      keratins. They also showed a wide range of reactivity with V9. However,
      neoplastic cells of five of the six SCC and five cases of BCC were negative for
      V9. These findings suggest that neoplastic cells of SCC-MU contain vimentin in
      higher frequency than in the more usual SCC.

PMID- 1385501
TI  - Spindle cell neoplasms coexpressing cytokeratin and vimentin (metaplastic
      squamous cell carcinoma).
AB  - Spindle cell squamous carcinoma (SCSC) and atypical fibroxanthoma (AFX) are both
      spindle cell neoplasms (SCN) that usually arise in areas of solar or ionizing
      radiation of elderly patients. Both lesions have a similar biologic behavior. In
      addition, the morphologic and ultrastructural similarities found in AFX and the
      spindle cell component of SCSC, have led some investigators to conclude that
      these tumors have a similar cell of origin. We studied 15 SCNs with no evidence
      of epithelial origin and no morphologic epithelial component, that showed
      immunohistochemical and ultrastructural evidence that would support metaplastic
      changes of a squamous cell carcinoma to a neoplasm with mesenchymal
      characteristics.

PMID- 1385503
TI  - Rat palatal histology related to denture-like appliances.
AB  - Two designs of palatal denture-like appliance were fitted to rats. Tooth- and
      tissue-borne appliances caused changes in epithelial thickness and keratin
      thickness, but these varied with anatomical site and type of appliance. A single
      inoculation of Candida albicans at the time of insertion of the appliance failed
      to establish infection consistently. Debris accumulation under the appliances was
      a problem which will restrict long-term studies with this model.

PMID- 1385502
TI  - A technique for three-dimensional microleakage assessment using tooth sections.
AB  - Microleakage is commonly assessed using restored teeth, sectioned through the
      midline of the restoration. It is impossible to determine if this is
      representative of the leakage throughout the whole tooth. This pilot study
      examined the feasibility of calculating areas and volumes of leakage using serial
      sections of restored teeth which had been subjected to dye immersion and image
      analysis. Using the sections, perspex models of the teeth were constructed to
      present the pattern of the dye leakage into dentine. This appears to be a viable
      technique for the three-dimensional assessment of microleakage.

PMID- 1385504
TI  - Medical humanities in nursing: thought provoking?
AB  - Medical humanities is an innovative way of learning. Discussing literary texts of
      nursing practice has been used to help students analyse attitudes, values and
      ethics; it has also been used to help practitioners review and reflect on their
      own experience and philosophy of nursing. In nursing education, it has been used
      to explore difficult issues in a safe environment. The value of this approach in
      nursing education and practice is that it can encourage reflection, promote self
      awareness and stimulate debate on difficult issues: for example, death and dying,
      power and institutionalization (of patients and staff) and pain. This paper gives
      a detailed worked example of how a literary text can be used in this way, the aim
      being to provide a resource which readers can then use with a group of students
      or colleagues. Finally, the authors explore the question of where medical
      humanities might have a place in the curriculum: as a lecture/tutorial in a
      course (e.g. Ethics), as a module in the curriculum, as a method of teaching
      nursing subjects (e.g. communication skills), as a discussion group (outside the
      curriculum), as a study guide, using literary texts alongside nursing text books.
      Any of these strategies can be a powerful vehicle for preserving the 'human
      factor' in both nursing education and continuing professional development.

PMID- 1385505
TI  - Effects of acute and chronic treatment with fluvoxamine on extracellular and
      platelet serotonin in the blood of major depressive patients. Relationship to
      clinical improvement.
AB  - The effects of the treatment with fluvoxamine (FVX) on platelet and plasma
      serotonin (5-HT) have been examined in eleven drug-free major depressive
      patients. Acute FVX was without effect, whereas the repeated oral treatment (100
      150 mg daily, 12 weeks) reduced platelet 5-HT (-89%, P less than 0.001) and
      plasma 5-HT (-60%, P less than 0.02). Patients who responded to the treatment at
      6 weeks (Hamilton score less than or equal to 10) had significantly lower (-39%,
      P less than 0.02) pretreatment values of platelet 5-HT than the rest. This
      suggests that 'low 5-HT' patients may have a more rapid improvement after
      fluvoxamine. Platelet 5-HT and HDRS correlated significantly along the treatment
      (r = 0.679, P less than 0.01). These data demonstrate a marked action of
      fluvoxamine as 5-HT uptake inhibitor at therapeutic doses and confirm that this
      mechanism is relevant for its efficacy as antidepressant drug.

PMID- 1385506
TI  - Transcatheter umbrella closure of valvular and paravalvular leaks.
AB  - OBJECTIVES: Our aim was to adapt the technique of transcatheter umbrella closure
      of intracardiac defects for closure of valvular and paravalvular defects.
      BACKGROUND: The double-umbrella device developed by Rashkind and Cuaso has been
      safely and effectively delivered across a host of intracardiac defects, but
      transcatheter closure of valvular and paravalvular leaks has not been reported.
      METHODS: Between February 1987 and September 1990, eight patients who were
      believed to be poor operative candidates were taken to the catheterization
      laboratory for transcatheter double-umbrella closure of a valvular or a
      paravalvular leak. Four patients had a paravalvular leak around a prosthetic
      aortic valve. The other four patients had a valvular leak: one patient with a
      regurgitant native aortic valve after a Stansel procedure and three patients with
      a regurgitant porcine valve in a left ventricular apex to descending aorta
      conduit. RESULTS: Placement of a double-umbrella device was attempted in seven of
      the eight patients and was successful in all seven. Device placement was not
      attempted in one patient because of the crescentic shape of his defect. Two
      patients required two devices for each closure; the other five required only one
      device each. Angiography, performed on six patients after device closure,
      demonstrated that three patients had a completely occluded defect, two had
      trivial residual flow and one patient had mild residual flow through the device.
      All significant complications occurred in one patient who had hemolysis and
      oliguria that resolved when the initial umbrella was replaced by a larger device.
      In addition, two devices migrated to the patient's pulmonary arteries but were
      retrieved in the catheterization laboratory without difficulty. No other early or
      late complications occurred in 21 to 50 months of follow-up. Of the four patients
      with a paravalvular leak, the one who did not receive a device died at operation,
      one patient died at operation for an associated defect (in the operating room the
      umbrella was found securely in place across the paraaortic defect) and two
      patients are clinically well at home after 21 and 32 months, respectively. Of the
      four patients with closure of a valvular leak, one patient remains well at home
      50 months later, one patient died at operation for associated defects and two
      patients had additional successful surgical treatment and remain well 29 months
      after device placement. CONCLUSIONS: Transcatheter umbrella closure appears to be
      a reasonable alternative for closure of a valvular or paravalvular leak in
      patients who are poor operative candidates.

PMID- 1385508
TI  - A survey of the vision assessment of the developmentally disabled and multi
      handicapped in University Affiliated Programs (UAPs).
AB  - In 1989 we conducted a survey to assess the availability of vision assessments
      (screening and complete eye/vision examinations) in University Affiliated
      Programs for Persons with Developmental Disabilities (UAPs). Analysis of the
      results suggests that although the UAPs are continuing to provide some services
      for eye/vision care, only 58 percent of these centers have facilities for the
      screening of vision problems. Ninety-six percent of the respondents, however,
      feel that vision screening is important. The developmentally disabled and multi
      handicapped child is at high risk for vision/eye problems. Unless this difference
      between service availability and the perceived importance of vision services is
      addressed, there is an increased risk that the child may not reach his/her full
      potential. The UAPs need to increase the availability of eye/vision care within
      the UAPs and to expand training to providers in the community to deal with the
      developmentally disabled and multi-handicapped.

PMID- 1385509
TI  - Acute and subacute toxicity of 7.5% hypertonic saline/6% dextran-70 (HSD) in
      dogs. 1. Serum immunoglobulin and complement responses.
AB  - Clinical use of modern dextran solutions has been limited by concerns of
      anaphylactoid reactions. To assess the short-term antigenic response to 7.5%
      hypertonic saline in 6% Dextran-70 (HSD), sera were obtained from dogs involved
      in the acute and subacute toxicology testing of HSD and its individual
      components, and analyzed for IgG, IgM and C3 complement. In separate studies,
      beagles were infused i.v. with a single dose of HSD or its components at 20 ml kg
      1 (the maximum tolerated dose; MTD), or the MTD daily for 14 days, and serum was
      obtained prior to and at various times after infusion up to 14 days. In both
      studies, despite serum dextran concentrations exceeding 2000 mg dl-1, no
      induction of IgG, IgM or C3 complement concentrations were observed. In addition,
      serum IgG immunoelectrophoretic patterns were of normal curvature, position and
      intensity; the immunoprecipitin bands were not displaced, bowed, inhibited or
      thicker than the normal preinfusion immunoelectrophoretograms. The data suggest
      that single or multiple HSD i.v. injections, as much as five times the proposed
      therapeutic level for the treatment of hypovolemia, evoked no increase in
      antibody titers in dogs. Therefore, therapeutic use of HSD in the treatment of
      hemorrhagic shock should not be associated with widespread concomitant allergic
      complications.

PMID- 1385507
TI  - Peptide-induced nonresponsiveness of HLA-DP restricted human T cells reactive
      with Dermatophagoides spp. (house dust mite).
AB  - The activation of CD4+ T lymphocytes, which play a central role in allergic
      inflammation, depends on the recognition of allergen-derived peptides in
      association with major histocompatibility complex class II gene products. In this
      report we demonstrate, at a clonal level, that a component of the T-cell
      repertoire reactive with Dermatophagoides spp. (house dust mite) in atopic
      individuals, is restricted by HLA-DP class II molecules. This supports the recent
      results emerging from genetic epidemiologic studies that indicate positive
      associations between the HLA-DP phenotype and immune responsiveness to a variety
      of common allergens. Our findings also reveal that the T cells restricted by HLA
      DP recognize a species-specific epitope located in the group I allergen of
      Dermatophagoides pteronyssinus (residues 101-119). Furthermore, we report that
      the pretreatment of the T cells restricted by HLA-DP with the Der p I peptide
      renders them nonresponsive to an immunogenic challenge with house dust mite
      allergen, and the loss of antigen-dependent proliferation is associated with
      downregulation of membrane expression of the T-cell antigen receptor. The ability
      to functionally inactivate T cells restricted by HLA-DP, as well as those that
      recognize allergen in association with HLA-DR class II molecules, suggests that
      desensitization with allergen-derived peptides may have therapeutic potential in
      the management of allergic diseases irrespective of their HLA class II
      association.

PMID- 1385510
TI  - Pulsatile release of histamine in the hypothalamus of conscious rats.
AB  - The pattern of histamine release was investigated in the hypothalamus of the
      conscious, freely moving rat over 20 h. Under anaesthesia, a guide cannula was
      stereotaxically inserted into the posterior hypothalamus. In the conscious
      animal, the stylet of the guide cannula was replaced by a push-pull cannula, and
      the hypothalamus was superfused with artificial cerebrospinal fluid. Histamine
      was determined radioenzymatically in the superfusate which was continuously
      collected in time periods of 20 min. The release rate of histamine fluctuated
      according to an ultradian rhythm (frequency: 1 cycle per 83 min) and a circadian
      rhythm with the highest release rate of histamine between 11:00 p.m. and 1:00
      a.m. The release rate of histamine during darkness was higher than that during
      the light period. The results demonstrate that, in the brain, neuronal histamine
      is released according to rhythms with various frequencies.

PMID- 1385511
TI  - Presence and regional variation in peptide-containing nerves in the human ureter.
AB  - The occurrence, distribution and regional variation of neurones immunoreactive
      for the neuropeptides, vasoactive intestinal polypeptide (VIP), neuropeptide Y
      (NPY), enkephalin (ENK), calcitonin gene-related peptide (CGRP), and substance P
      (SP) were investigated in human ureters by indirect immunohistochemistry. In
      addition, immunoreactivities to tyrosine hydroxylase (TH), a marker of
      noradrenergic neurones and to protein gene product (PGP) 9.5, a general marker of
      neurones, were also studied. Neurones displaying PGP-, NPY-, VIP- and TH-like
      immunoreactivity (-LIR) provided a rich innervation to the smooth muscle and
      blood vessels of the ureter, where they formed dense muscular and perivascular
      nerve plexuses. In contrast, there was only a moderate to sparse innervation by
      SP and CGRP-LIR neurones, most of which were distributed to blood vessels and to
      the sub mucosal layer, and only rarely to smooth muscle bundles. No ENK-LIR was
      detected in this study. Nerve fibre bundle densities were estimated for each of
      the localized neurochemicals according to a method described. NPY-LIR nerve fibre
      bundles were found to account for 80% of the total nerve fibre bundles (i.e. PGP
      LIR) in the ureter. On the other hand, TH-LIR and VIP-LIR nerve fibre bundles
      each accounted for 50% of the total ureteral innervation, whereas SP- and CGRP
      LIR nerve fibre bundles each comprised 20% of the total innervation. The
      abundance and pattern of tissues innervated by these immunoreactive neurones is
      consistent with the view that some of these neuropeptide substances co-exist with
      other peptide substances and/or with other known neurotransmitters, such as
      noradrenaline or acetylcholine. A gradient of innervation was found to exist for
      all the neurochemicals demonstrated in the ureter, whereby the lower ureter
      receives a greater density of innervation than the upper ureter. This finding
      suggests the human ureter is primarily innervated by fibres arising from or via
      the lower pelvis, i.e. the pelvic plexus. It also supports the view that the
      lower ureter may perform an important physiological role, such as coordinating
      the tone of this region during bladder filling and emptying.

PMID- 1385512
TI  - [Macular involvement in angioid streaks. Gronblad-Strandberg syndrome].
AB  - Between 1971 and 1988, we examined 116 eyes of 58 patients with Gronblad
      Strandberg syndrome in private practice and in the Retinal Department of the Eye
      Clinic, Faculty of Medicine, Ankara University. There was initial macular
      involvement in 79% of cases with angioid streaks. The most frequently encountered
      lesion, found in 53% of the cases, was choroidal neovascularization. Macular
      involvement had become bilateral in 80% of the cases after 12.5 months median
      follow up. Thirteen of the 50 eyes with choroidal neovascularization were treated
      by argon or red krypton laser photocoagulation. Vision decreased during follow-up
      in 15% of the 13 eyes treated whereas it decreased in 32% of the 69 eyes
      unsuitable for laser treatment.

PMID- 1385513
TI  - Breast cancer screening in older women: law and patient rights.
AB  - Legal principles that apply to breast cancer in older women have been developed
      in judicial decisions related to other medical screening tests. There are no
      special legal rules for either mammography or older women, although older women
      seldom file malpractice suits. The general standard is that a screening test must
      be offered to any particular age group when it is considered "reasonably prudent"
      to do so, and this almost always means when the medical profession--usually
      speaking though its specialty boards--declares it the standard of care. The
      standard of care should be set by medical professionals, with open opportunity
      for public input, rather than by lawyers or risk managers. In actual practice,
      private regulation may not be sufficient to protect the public, and both state
      and federal regulation of mammography facilities now seems inevitable. Patients
      have the right to be fully informed prior to screening, the right to refuse
      screening, and the right to have full knowledge of the consequences of such
      refusal. Mammography is not a consumer good, but American women should be
      actively involved in determining issues of costs and benefits, as well as helping
      to develop the best strategies for counseling and informed consent.

PMID- 1385514
TI  - Suicide risk and serotonin.
AB  - The accumulating research evidence for the psychobiological reconceptualization
      of suicidal behaviour is briefly reviewed, particularly regarding the serotonin
      hypothesis of suicide risk. The first suggestion of a link between suicide and
      serotonin came with the biochemical results from postmortem brain studies of
      suicide victims. Currently available research data suggest decreased brain stem
      levels of serotonin and 5-HIAA, altered distribution of presynaptic binding of
      the ligand 3H-imipramine to serotonin neurons and a region-specific increase in
      the number of postsynaptic 5HT2 receptors in the prefrontal cortex in suicide
      victims. Early CSF studies have indicated decreased CSF 5-HIAA in patients
      recently attempting suicide and follow-up studies of large samples of mood
      disorder patients confirm the original hypothesis that low CSF 5-HIAA predicts
      suicide risk after attempted suicide. However, the clinical utility of these
      compelling biological correlates of suicide in the management of suicide risk in
      psychiatric patients will depend on the results of psychopharmacological
      treatment research targeting suicidal behaviour.

PMID- 1385515
TI  - Epitope-selected monospecific antibodies to recombinant antigens from Toxoplasma
      gondii reacted with dense granules of tachyzoites.
AB  - Epitope-selected monospecific antibodies were applied to investigate the
      localization of antigenic molecules in Toxoplasma gondii by immunoelectron
      microscopy. Eighty cDNA clones encoding antigenic polypeptides were
      immunoscreened from lambda gt11 expression library with T. gondii infected mouse
      sera. Twenty different clones with no crossreactivity were selected from eighty
      clones. Monospecific antibodies to antigens derived from respective cDNA clones
      extracted from infected mouse sera by the epitope selection method were used in
      Western blot analysis and immunoelectron microscopy. Eleven antigens were
      detected with epitope-selected antibodies in lysates of T. gondii tachyzoites.
      Five of the antigens with molecular weights of 60, 40, 35, 28, and 27 KD were
      localized in the dense granules. Monospecific antibodies purified by the epitope
      selection method were useful for investigating the localization of antigens
      without preparation of a monoclonal antibody from a hybridoma.

PMID- 1385516
TI  - Fc-mediated nonspecific staining of the porcine brain with rabbit antisera in
      immunocytochemistry is prevented by pre-incubation of the sera with proteins A
      and G.
AB  - Nonspecific staining was detected in immunocytochemical procedures on the porcine
      hypothalamus with rabbit antisera, irrespective of the antigen specificity of the
      sera, in magnocellular neurons of the paraventricular (PVN) and supraoptic nuclei
      (SON), and in the vasopressin- and oxytocin-containing nucleus (VON). The present
      study was designed to test the hypothesis that this staining is mediated by the
      Fc portion of rabbit immunoglobulins. Rabbit antisera against neuropeptides
      localized predominantly outside the PVN, SON, and VON were employed in
      combination with different detection methods. The intensity of the nonspecific
      staining varied depending on the antiserum and persisted after pre-absorption of
      the antisera with their homologous peptides. Nonspecific staining and antigen
      specific staining were differentially affected by the method of tissue fixation.
      The nonspecific staining could be prevented by preincubation of the antisera with
      proteins A and G, which left the antigen-specific staining intact, whereas
      additional preabsorption with homologous peptide abolished all staining. These
      observations suggest that the Fc region of IgGs is indeed involved in the
      nonspecific staining. On press-blots of homogenates from SON tissue subjected to
      isoelectric focusing, one band in the low-pH region was found with all antisera.
      Pre-incubation of the antisera with protein A abolished the staining of this band
      but did not affect staining of antigen-specific bands. Pre-incubation with
      proteins A and G is proposed as a routine control to check for nonspecific
      staining mediated by the Fc region of IgGs in immunocytochemical procedures,
      particularly those that employ rabbit sera in porcine brain.

PMID- 1385517
TI  - Monoclonal antibodies specific to quail embryo tissues: their epitopes in the
      developing quail embryo and their application to identification of quail cells in
      quail-chick chimeras.
AB  - Quail-chick chimeras have been used extensively in the field of developmental
      biology. To detect quail cells more easily and to detect cellular processes of
      quail cells in quail-chick chimeras, we generated four monoclonal antibodies
      (MAb) specific to some quail tissues. MAb QCR1 recognizes blood vessels, blood
      cells, and cartilage cells, MAb QB1 recognizes quail blood vessels and blood
      cells, and MAb QB2 recognizes quail blood vessels, blood cells, and mesenchymal
      tissues. These antibodies bound to those tissues in 3-9-day quail embryos and did
      not bind to any tissues of 3-9-day chick embryos. MAb QSC1 is specific to the
      ventral half of spinal cord and thymus in 9-day quail embryo. No tissue in 9-day
      chick embryo reacted with this MAb. This antibody binds transiently to a small
      number of brain vesicle cells in developing chick embryo as well as in quail
      embryo. A preliminary application of two of these MAb, QCR1 and QSC1, on quail
      chick chimeras of neural tube and somites is reported here.

PMID- 1385519
TI  - Characteristics of murine monoclonal anti-CD4. Epitope recognition, idiotype
      expression, and variable region gene sequence.
AB  - We have characterized a series of mouse monoclonal anti-CD4 and describe both
      their CD4 epitope recognition and Id expression. We also determined the V region
      gene sequences of these antibodies in an attempt to correlate epitope recognition
      and Id expression with V region sequence. All of these preparations recognize
      epitopes that cluster around the HIV gp120 binding site on the human CD4
      molecule. However, we observed differences in epitope recognition among the anti
      CD4 preparations, based on either competitive inhibition assays or functional
      assays, such as syncytium inhibition. Analysis of Id specificities using a
      polyclonal anti-Id generated against anti-Leu 3a indicated that five of the seven
      monoclonal anti-CD4 expressed a shared Id. Based on V region gene sequences, the
      V region kappa-chain (V[kappa]) from each of the seven antibodies was encoded by
      the V[kappa]21 gene family and expressed the J[kappa]4 gene segment. Those
      preparations that expressed the shared Id with anti-Leu 3a have virtually
      identical V[kappa] sequences, with a high degree of homology in the CDR. The VH
      region gene sequences of six of the seven antibodies also shared overall homology
      and appeared to be encoded by the J558 VH gene family. The seventh anti-CD4 VH
      region is encoded for by the VHGAM gene family. The majority of these antibodies
      used JH3 gene segment, although the JH2 and JH4 gene segments were also
      represented. In addition, several of these antibodies share a common sequence
      organization within their V-D-J joining regions that appears to involve N and P
      sequences to generate unique D segments. Together, these data suggest that
      differences in epitope recognition among the monoclonal anti-CD4 may reflect
      sequence variability primarily within the CDR3 region of both V[kappa] and VH.
      The basis for the detection of a shared Id most likely reflects the high degree
      of homology within the V[kappa] region sequences. In addition, these data, which
      are based on a limited analysis, suggest the possible restricted use of V region
      germ-line gene families in the secondary antibody response of BALB/c mice to
      specific epitopes on the human CD4 molecule.

PMID- 1385518
TI  - B7 costimulates proliferation of CD4-8+ T lymphocytes but is not required for the
      deletion of immature CD4+8+ thymocytes.
AB  - In addition to TCR-derived signals, costimulatory signals derived from
      stimulation of the CD28 molecule by its natural ligand, B7, have been shown to be
      required for CD4+8- T cell activation. We investigate the ability of B7 to
      provide costimulatory signals necessary to drive proliferation and
      differentiation of virgin CD4-8+ T-cells that express a transgenic TCR specific
      for the male (H-Y) Ag presented by H-2Db class I MHC molecules. Virgin male
      specific CD4-8+ T cells can be activated either with B7 transfected chinese
      hamster ovary (CHO) cells and T3.70, a mAb specific for the transgenic TCR-alpha
      chain that is associated with male-reactivity, or by male dendritic cells (DC).
      Activated CD4-8+ T cells proliferated in the absence of exogenously added IL-2.
      IL-2 activity was detected in supernatants of CD4-8+T3.70+ cells that were
      stimulated with T3.70 and B7+CHO cells. The response of CD4-8+T3.70+ cells to
      T3.70/B7+CHO or to male DC stimulation were inhibited by CTLA4Ig, a fusion
      protein comprising the extracellular portion of CTLA4 and human IgG C gamma 1. It
      has been previously shown that CTLA4Ig binds B7 with high affinity. Staining with
      CTLA4Ig revealed that DC express about 50 times more B7 than CD4-8+ T cells.
      CTLA4Ig also specifically blocked the proliferation of male-reactive cells in
      vivo. We have also used an in vitro deletion assay whereby immature CD4+8+
      thymocytes expressing the transgenic male-specific TCR are deleted by overnight
      incubation with either immobilized T3.70 or male DC to investigate the
      participation of the CD28/B7 pathway in the negative selection of immature
      thymocytes. Staining with B7Ig established that both immature murine CD4+8+ and
      mature CD4-8+ thymocytes express a high level of CD28. However, despite the high
      expression of CD28 on CD4+8+ thymocytes, it was found that deletion of CD4+8+
      thymocytes expressing the male-specific TCR by the T3.70 mAb was not inhibited by
      B7+CHO cells. Furthermore, the deletion of these thymocytes by DC also was not
      inhibited by CTLA4Ig. These findings provide evidence that although signaling
      through CD28 can costimulate a primary anti-male response in mature CD4-8+ T
      cells, the CD28/B7 pathway does not appear to participate in the negative
      selection of immature CD4+8+ thymocytes.

PMID- 1385520
TI  - Cytokines increase transporter in antigen processing-1 expression more rapidly
      than HLA class I expression in endothelial cells.
AB  - Transporter in Ag processing-1 (TAP-1, previously called PSF-1 or Ring-4) is an
      MHC-encoded gene product that is required for efficient association of
      intracellular peptide Ag with nascent HLA class I H chain and beta 2
      microglobulin, thereby permitting assembly and normal surface expression of the
      class I molecules. TAP-1 is thought to function as a component of a transmembrane
      pump, that transports cytoplasmically-derived peptides into the lumen of the
      endoplasmic reticulum where class I molecules assemble. Synthesis and expression
      of HLA class I molecules is increased in human endothelial cells by IFN-beta, IFN
      gamma, and TNF. We report these same cytokines increase TAP-1 expression. As with
      class I, TAP-1 is also synergistically increased by combinations of TNF with IFN.
      Interestingly, cytokine-induced increases in TAP-1 mRNA are markedly more rapid
      than increases in class I mRNA. This rapid increase in TAP-1 mRNA is reflected in
      a rapid increase in TAP-1 protein. These results demonstrate that TAP-1 synthesis
      and class I synthesis are regulated in parallel. The rapidity of the cytokine
      response of TAP-1 compared to class I further suggests that the constitutive
      level of TAP-1 expression in endothelial cells is not sufficient to support
      inducible increases in class I expression.

PMID- 1385521
TI  - Neuropeptides modulate human eosinophil chemotaxis.
AB  - To investigate the role of neuropeptides in allergic inflammation, we examined
      the effect of peptides on eosinophil chemotaxis. Eosinophils were purified from
      the blood of allergic and normal subjects using a discontinuous Percoll density
      gradients. Chemotaxis was induced by platelet-activating factor (PAF) and
      leukotriene B4, and was assayed by a modified Boyden's chamber technique. Four
      neuropeptides were examined in this study: substance P (SP), neurokinin A,
      calcitonin gene-related peptide (CGRP), and cholecystokinin octapeptide. Peptides
      alone (10 nM to 10 microM) were not chemotactic for eosinophils. However, when
      eosinophils were pre-treated with peptides (100 nM) at 37 degrees C for 30 min,
      chemotactic response to PAF (10 nM) was significantly enhanced (p < 0.01) in
      allergic subjects; % control by SP, neurokinin A, CGRP and cholecystokinin
      octapeptide was 269 +/- 42, 243 +/- 32, 227 +/- 21, and 251 +/- 42, respectively
      (n = 8). Similar results were obtained in leukotriene B4-induced eosinophil
      chemotaxis. In contrast, no enhancement was observed in normal subjects.
      Potentiating effect of SP and CGRP on PAF-induced eosinophil chemotaxis in
      allergic subjects was significantly attenuated by SP antagonist [D-Pro2,D-Trp7,9]
      SP and human CGRP (8-37) receptor antagonist, respectively. Neutral endopeptidase
      inhibitors (phosphoramidon, leupeptin, and bestatin) failed to significantly
      augment the PAF-induced eosinophil chemotaxis when the cells were pretreated with
      various peptides and neutral endopeptidase inhibitors. The C-terminal fragment of
      SP (SP6-11) had an effect similar to that of the intact SP molecule, whereas no
      potentiating effect by the N-terminal of SP (SP1-9) was observed. These results
      suggest that neuropeptides may play a significant role in eosinophil infiltration
      by priming cells in allergic inflammation.

PMID- 1385522
TI  - Control of acute infection with lymphocytic choriomeningitis virus in mice that
      cannot present an immunodominant viral cytotoxic T lymphocyte epitope.
AB  - For controlling infection of the mouse with the lymphocytic choriomeningitis
      (LCM) virus, CD8+ CTL are essential. In the infected BALB/c mouse the arising LCM
      virus-specific CTL are exclusively restricted by the class I MHC-encoded molecule
      L; K- or D-restricted antiviral CTL cannot be detected. Thus, the infected L
      deficient BALB/c mutant C-H-2dm2 should not be capable of eliminating the virus.
      The experimental evidence proves the contrary, which is explained by K- and D
      restricted CTL that this mouse generates. Why such cells remain undetectable in
      BALB/c mice is currently unexplained, because there is no lack of precursors and
      the corresponding virus Ag is presented. Despite the absence of lytic activity in
      vitro, other than the one associated with L, transfusion of day 8-immune spleen
      cells from BALB/c into infected C-H-2dm2 (L-deficient) mice results in
      accelerated virus elimination from the organs of the latter, which was manifest
      as soon as 8 h after cell transfer. Furthermore, lytic activity did not attain
      measurable levels in the recipients' spleens. Obviously, this infection can be
      terminated by CD8+ T lymphocytes even when these cells' lytic activity is below
      detectability.

PMID- 1385523
TI  - Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons
      with chronic hepatitis.
AB  - Hepatitis C virus (HCV) is a major cause of post-transfusion and sporadic
      hepatitis worldwide, leading to chronic liver disease in at least 50% of infected
      individuals. The pathogenic mechanisms that result in chronic hepatitis are
      unknown. Lymphocytes are typically observed within the hepatic parenchyma, but
      the functional characteristics of these cells have not been defined. In this
      study, liver-infiltrating lymphocytes from two subjects with chronic HCV
      hepatitis were cloned at limiting dilution and tested for HCV-specific cytolytic
      activity using autologous target cells infected with vaccinia viruses expressing
      recombinant HCV Ag or sensitized with synthetic HCV peptides. In both subjects,
      HCV-specific, HLA class I-restricted CTL were identified that recognized epitopes
      in variable regions of either the envelope or nonstructural proteins. These
      results demonstrate the presence of HCV-specific CTL at the site of tissue damage
      in persons with chronic HCV hepatitis, and provide a means to evaluate the
      possible pathogenic role of these cells in HCV infection.

PMID- 1385524
TI  - Immunization of mice with lipopeptides bypasses the prerequisite for adjuvant.
      Immune response of BALB/c mice to human immunodeficiency virus envelope
      glycoprotein.
AB  - In vivo priming of CTL requires the association with MHC class I molecules of
      peptides derived from the processing of endogenously produced proteins.
      Immunization with exogenous proteins or peptides rarely induces MHC class I
      restricted CTL unless they are associated with lipidic compounds. The capacity to
      induce CTL was compared in synthetic peptides and simple lipopeptides containing
      the Immunodominant MHC class I H-2Dd-restricted T-cell epitope of HIV-1 gp160. In
      contrast with free peptides in saline, lipopeptides induced strong primary CTL
      responses in vivo. These CTL were able to lyse cells infected with a recombinant
      vaccinia virus expressing the HIV-1 env gene. Priming of CTL was also successful
      when using 16-amino acid lipopeptides as 34-amino acid lipopeptides, suggesting
      that several epitopes might be included in a single construct. In vivo priming of
      CTL also requires CD4+ T cell help. We therefore searched for Th cell activation
      after priming with lipopeptides. Our results show that, as with CTL induction, Th
      cell activation with lipopeptides did not require mixing with adjuvant. In
      addition, lipopeptides were also efficient at stimulating antibody-mediated
      responses. Our results show that a single lipopeptidic construct can induce a
      total immune response, which is of importance in vaccine development.

PMID- 1385525
TI  - B cell deficiency progresses with lineage maturation in nude.X-linked
      immunodeficient mice B cell deficiency progresses with lineage maturation.
AB  - Previously we showed that unlike normal, nude, or X-linked immune deficient (xid)
      mice, nude.xid mice are deficient in bone marrow pre-B cell targets for Abelson
      murine leukemia virus transformation. We show that nude.xid bone marrow is
      deficient in both CD45(B220)+ and CD45(B220)- surface (s)IgM- progenitors that
      give rise to B cell colonies in Whitlock-Witte cultures. CD45(B220)+ precursors
      had normal differentiation potential in vitro. CD45(B220)- precursors
      differentiated into CD45(B220)+ cells at the same rate as normal controls, but
      acquired sIgM at a much slower rate. These results correlated with the
      observation that in nude.xid mice the severity of B lineage defects correlates
      with maturity: a profound (ninefold) deficit of sIgM+, CD45(B220)+ mature B
      cells, a fivefold deficit in the sIgM-, CD45(B220)+ precursors of short term B
      cell colonies (colonies forming within 4-5 days in Whitlock-Witte cultures), and
      a moderate (twofold) decrease in the frequency of sIgM-, CD45(B220)- (less
      mature) precursors of long term B cell colonies (colonies forming after 14 days
      of Whitlock-Witte culture. Thus the combination of the nude and xid mutations
      produces a deficiency in early B cell progenitors and the deficiency becomes more
      profound with further maturation. Therefore the lack of mature B cells is the
      result of a cascade effect. Inasmuch as bone marrow progenitors are affected, and
      these are the source of the vast majority of B cells, most B cells are affected
      by the xid mutation and the xid defect cannot be attributed to a loss of a fetal
      lineage of B cells. These results suggest that xid affected cells lack the
      capacity to progress efficiently through differentiation in the absence of an
      exogenous factor(s) that is dependent on the product of a normal allele at the
      nude locus. This product might be supplied in vivo by a T cell or T cell
      dependent source and/or epithelial elements such as bone marrow stromal cells all
      of which are known to be affected by the nude mutation.

PMID- 1385526
TI  - Superantigen and HLA-DR ligation induce phospholipase-C gamma 1 activation in
      class II+ T cells.
AB  - Bacterial enterotoxin superantigens bind directly to HLA class II molecules (HLA
      DR) expressed on both APC and activated human T cells, and simultaneously bind to
      certain V beta chains of the TCR. In this report, we compared early T cell
      signaling events in human alloantigen-stimulated T cells when activated by HLA-DR
      ligation through antibody cross-linking or by direct enterotoxin superantigen
      binding. Both types of stimuli induced tyrosine phosphorylation of
      phosphatidylinositol-specific phospholipase C gamma 1 (PLC gamma 1) and an
      increase in intracellular calcium concentration; however, superantigen-induced
      signaling was stronger than class II ligation alone. Antibody-mediated ligation
      of HLA-DR with CD3 resulted in augmented PLC gamma 1 activation and increased
      calcium mobilization, consistent with a mechanism of superantigen activity
      through a combination of class II and CD3/Ti signals. In addition, down
      modulation of CD3 receptors with antibody demonstrated that superantigen-induced
      signaling events were CD3-dependent. Superantigen signaling was also class II
      dependent, in that resting T cells were not responsive to direct enterotoxin
      stimulation. To address how early signal transducing activity correlated with T
      cell responsiveness, alloantigen-primed T cells were activated with immobilized
      class II-specific mAb or soluble superantigen. Both HLA-DR mAb-stimulated T cells
      and enterotoxin-treated T cells proliferated strongly in response to co
      stimulation by a combination of CD28 receptor engagement and PMA addition. In
      addition, superantigen-induced growth was induced by CD28 receptor ligation with
      antibody or the B7 counter-receptor expressed on Chinese hamster ovary cells.
      Taken together, these results indicate that class II molecules expressed on
      activated T cells are directly coupled to the PLC gamma 1 signal transduction
      pathway, and that coligation of HLA-DR with CD3 augments T cell signaling
      comparable to that induced by enterotoxin superantigen. Thus, we suggest that
      superantigen-induced early signaling responses in activated T cells may be due in
      part to class II transmembrane signals induced when HLA-DR and V beta are ligated
      in cis.

PMID- 1385527
TI  - Signal transduction through decay-accelerating factor. Interaction of glycosyl
      phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1.
AB  - Decay-accelerating factor (DAF or CD55) is a 70-kDa glycosyl-phosphatidylinositol
      (GPI)-anchored protein that protects cells from complement-mediated lysis by
      either preventing the formation of or dissociating C3 convertases. Cross-linking
      of DAF on human peripheral T cells by polyclonal antibodies has previously been
      reported to lead to lymphocyte proliferation. Two mAb, both mapping to the third
      short consensus repeat region of DAF, were able to trigger proliferation of human
      peripheral T cells. To determine the role of the GPI anchor in cell activation,
      we transfected EL-4 murine thymoma cells with cDNA encoding either DAF or a
      transmembrane form of DAF (DAF-TM). The DAF-transfected cells were able to
      transduce late activation events as evidenced by IL-2 production, whereas DAF-TM
      transfected cells were unable to do so. The GPI-anchored DAF was able to
      transduce early activation events leading to the tyrosine phosphorylation of a 40
      kDa protein and several proteins in the 85-95 kDa range--an event absent in DAF
      TM-transfected cells. Furthermore, anti-DAF immunoprecipitates of DAF-transfected
      cells contain tyrosine kinase activity leading to the phosphorylation of 40-, 56
      60-, and 85-kDa proteins, whereas anti-DAF immunoprecipitates of DAF-TM
      transfected cells did not have an associated kinase activity. Both p56lck and
      p59fyn were associated with DAF in DAF-transfected EL-4 cells. In HeLa cells
      transfected with fyn, DAF associated with p59fyn. This complex of DAF with src
      family protein tyrosine kinases requires the GPI anchor and suggests a pathway
      for signaling through GPI-anchored membrane proteins.

PMID- 1385528
TI  - Serologic cross-reactivities poorly reflect allelic relationships in the HLA-B12
      and HLA-B21 groups. Dominant epitopes of the alpha 2 helix.
AB  - Previous analysis has emphasized the correlation between primary structures of
      class I HLA molecules and their patterns of serologic cross-reactivity. Here we
      describe the structures of two serologic groups of HLA-B alleles for which this
      is not the case. HLA-B45, an allele associated with black populations, is
      serologically paired with B44 in the B12 group; its structure, however, is
      divergent from that of B44 but closely related to B50. The BN21 (B*4005) allele
      is associated with native Americans and is serologically grouped with B50 in the
      B21 group; its structure, however, is more closely related to alleles of the B40
      group. The B44 and B45 serologically cross-reactive molecules differ at seven
      functional positions of the Ag recognition site; the B50 and BN21 molecules
      differ at four such residues. These differences are predicted to alter peptide
      presentation and be capable of eliciting strong alloreactive T cell responses.
      For these pairs of B12 and B21 Ag, serology appears dominated by epitopes formed
      by short sequences of the alpha 2 helix which have been shuffled by recombination
      between alleles. The implications of these results for HLA matching in
      transplantation are discussed.

PMID- 1385529
TI  - IL-3-dependent mast cells attach to plate-bound vitronectin. Demonstration of
      augmented proliferation in response to signals transduced via cell surface
      vitronectin receptors.
AB  - The adhesive interactions of activated mast cells with the extracellular matrix
      play an important role in anchorage and cellular motility. In this report we
      demonstrate that IL-3-dependent bone marrow-derived mast cells adhere to plate
      bound vitronectin with high affinity in a saturable and dose-dependent manner.
      This adhesion interaction is unique in that it does not require prior mast cell
      activation through Fc epsilon RI or after treatment with PMA. It is inhibited by
      divalent cation chelation and by competitive inhibition with a synthetic Arginine
      Glycine-Aspartate-Serine tetrapeptide. Polyclonal antisera for alpha v beta 3, an
      integrin known to bind vitronectin, inhibits attachment to plate-bound
      vitronectin in a dose-dependent manner. Comparison of the adhesion interactions
      for vitronectin, fibronectin, and laminin indicate that adhesion to vitronectin
      is greater than that seen with either fibronectin or laminin, either in the
      presence or absence of PMA. FACS analysis using a monoclonal hamster anti-murine
      vitronectin receptor (alpha v) antibody followed by a fluorescein-conjugated
      rabbit anti-hamster IgG revealed no change in surface vitronectin receptor
      expression after Fc epsilon RI-mediated cell activation. Proliferation assays
      with correction for cell viability revealed a 25% increase in cell number above
      the maximal IL-3 response over a 24-h period of adhesion to a vitronectin-coated
      surface and a 41% increase over 96 h of adhesion to vitronectin. Binding to plate
      bound vitronectin was not able to sustain cell viability in the absence of IL-3.
      Thus, IL-3-dependent bone marrow-derived mast cells adhere to vitronectin, an
      extracellular matrix protein present throughout connective tissues. This
      interaction generates a signal that results in the augmentation of the maximal IL
      3-dependent mast cell proliferative response, thus demonstrating at least one way
      in which the interaction between mast cells and extracellular matrix alter the
      biologic responsiveness of the mast cell.

PMID- 1385530
TI  - Differential expression of apoptosis-related Fas antigen on lymphocyte
      subpopulations in human peripheral blood.
AB  - The Fas Ag is a newly defined cell-surface molecule that may mediate apoptosis.
      The antibody against Fas Ag can induce the apoptotic cell death in cell lines
      expressing this Ag. PBL subpopulations at various ages were here examined for Fas
      expression by two-or three-color flow-cytometric analyses using anti-Fas mAb. It
      was found that Fas Ag was appreciably detected on a proportion of T and B cells,
      whereas its expression was absent for NK cells. For CD4+ and CD8+ T cells, Fas Ag
      was expressed preferentially on CD45RO+ (memory or previously activated)
      populations, but not on CD45RO- naive ones. TCR-gamma/delta+ T cells, especially
      their CD45RO+ subsets, also expressed Fas Ag. Expectably, neonatal T cell
      subpopulations, most of which had the naive (CD45RO-) phenotype, expressed little
      Fas Ag. Fas-expressing B cells dominated in surface(s) IgD- populations, but
      neonatal B cells as well as adult sIgD+ B cells had little Fas Ag. The Fas Ag was
      inducible after in vitro mitogenic stimulation of naive T and B cells from
      neonatal blood. These observations suggested that expression of Fas Ag on T and B
      cells in the peripheral blood might reflect their in vivo Ag-activated status. In
      contrast to Fas-expressing cultured cell lines, however, viability of in vitro
      stimulated T and B cells as well as freshly isolated CD45RO+ T cells was not
      significantly changed after the treatment with anti-Fas mAb, indicating that
      additional cellular conditions to Fas expression might be required for anti-Fas
      induced cell death.

PMID- 1385532
TI  - Cross-reactive antigen recognition by an encephalitogenic T cell receptor.
      Implications for T cell biology and autoimmunity.
AB  - The dominant immune response to rat myelin basic protein in H-2u mice is directed
      against the acetylated, N-terminal peptide Ac1-11 (AcASQKR-PSQRHG). This peptide
      causes encephalomyelitis on injection into mice of the H-2u haplotype. Only two
      residues of the peptide are required for ligation of the TCR from an Ac1-11
      specific T cell hybridoma. Proline at position 6 could not be substituted by any
      other L-amino acid, whereas glutamine at position 3 could be replaced by
      phenylalanine, histidine, methionine, or tyrosine. Cross-reactive recognition of
      these residues appears to be specific, because increasing the affinity of each
      analogue for its MHC restriction element, by replacing lysine with tyrosine at
      position 4, did not alter the pattern of cross-reactivity. For the majority of
      substitutions at this position, a lack of stimulation could not be explained by
      failure to bind to I-Au. However, competition binding studies showed that
      introduction of proline at position 3 reduced the efficacy of binding to I-Au.
      Cross-reactive analogues of Ac1-11 were injected into H-2u mice to test the
      extent to which cross-reactive T cell activation might lead to autoimmune disease
      in this model. An analogue containing methionine at position 3 caused clinical
      experimental autoimmune encephalomyelitis in a small percentage of H-2u mice.

PMID- 1385531
TI  - Inhibition of human bone marrow lymphoid progenitor colonies by antibodies to VLA
      integrins.
AB  - Studies in animal models suggest that the integrin adhesion protein VLA-4 may
      play an important role in lymphopoiesis. The relationship between cell adhesion
      and lymphopoiesis in humans has been difficult to study because of the relative
      rarity and stringent in vitro growth requirements of lymphoid progenitors from
      normal adult human bone marrow. To determine the functional significance of VLA-4
      mediated adhesion in human lymphopoiesis, we developed a culture system in which
      a bone marrow-derived adherent layer supports the formation of colonies of
      terminal deoxynucleotidyl transferase (TdT)-positive lymphoid precursor cells
      from normal adult human bone marrow. Limiting dilution studies were consistent
      with clonal origin of these colonies. CFU-TdT were enriched in the CD34+ bone
      marrow fraction, consistent with CD34 expression by other hematopoietic
      progenitors. CD34 expression and lack of lineage-specific markers in a
      significant proportion of the TdT+ colony cells suggest that the TdT+ CFU may
      represent an uncommitted lymphoid progenitor cell. Development of TdT+ colonies
      required direct contact with the adherent layer and was significantly inhibited
      by specific anti-VLA-4 alpha chain antibody, suggesting a functional role for the
      previously reported VLA-4-dependent adhesion of human B cell precursors to bone
      marrow-derived fibroblasts.

PMID- 1385533
TI  - Antibodies to soluble human T cell receptor beta chain recognize multiple
      epitopes on cell surface TcR.
AB  - The T cell receptor (TcR) is an integral membrane protein occurring as a
      disulfide linked heterodimer, non-covalently associated with CD3 on the surface
      of T lymphocytes. Antibodies to the TcR have been shown to be effective for
      treating autoimmune disorders in animals. We describe here a method for producing
      antibodies to cell surface determinants of the human TcR, using a soluble form of
      the receptor as antigen. Soluble V alpha 1.2, V beta 8.1, V beta 11 TcR chains
      are expressed from a construct in which the extracellular domains of the TcR are
      fused to the mouse gamma 2a heavy chain constant region lacking the CH1 domain.
      These chimeric molecules contain both immunoglobulin and TcR determinants, as
      revealed by antibody probes. Amino-terminal sequence analysis of a chimeric V
      beta 8.1 molecule indicates that the TcR leader peptide is correctly processed
      from the soluble form. Antibodies raised against the soluble human V beta 8.1
      molecule recognize the native determinants on Jurkat cells, and on natural T
      cells derived from resting human peripheral blood lymphocytes. Epitope mapping
      studies using competitive binding assays suggest that the anti-V beta 8
      antibodies produced using soluble antigen recognize multiple overlapping
      determinants on the cell surface form of the TcR.

PMID- 1385534
TI  - Preparative-scale purification and characterization of MHC class II monomers.
AB  - The MHC class II molecule is a heterodimeric glycoprotein consisting of one alpha
      and one beta polypeptide chain of almost identical molecular size. Recently it
      has been shown by others, and confirmed in our laboratory, that isolated monomers
      of murine MHC II molecules are capable of binding antigenic peptides like the
      alpha/beta intact heterodimer. In addition, preliminary results from our
      laboratory indicate that isolated single chain-peptide complexes of murine MHC
      class II molecules are capable of stimulating cloned T cells in an antigen
      specific manner. These results prompted us to isolate relatively large quantities
      of individual alpha and beta subunits of MHC II molecules for further in vitro
      and in vivo studies. Isolation of alpha and beta monomers proved to be difficult
      using conventional chromatographic methods. In this report we describe micro
      preparative and preparative continuous flow electrophoresis methods by which
      milligram quantities of MHC II subunits can be purified. An optimal condition for
      the dissociation of heterodimeric MHC II into alpha and beta monomers was
      identified, and separation of human HLA DR2 and murine IAs monomers was
      accomplished. Both methods offer the resolving power of gel electrophoresis with
      the convenience of continuous sample elution. Purified MHC II subunits obtained
      by these methods were tested for their ability to bind antigenic peptides.
      Results presented in this study indicate that monomeric subunits of both human
      HLA-DR2 and murine IAs are equally active in specific binding of antigenic
      peptides like the native heterodimer.

PMID- 1385535
TI  - An enzyme-linked immunosorbent assay for the quantification of solubilized CD14
      in biological fluids.
AB  - A simple and robust two site-binding ELISA for the quantification of solubilized
      CD14 in human and animal body fluids is described. The principle of the assay
      depends on the specific binding of sCD14 to two monoclonal antibodies (MEM-18,
      RoMo-1) recognizing different epitopes of this glycoprotein. The detection limit
      for sCD14 was 1 ng/ml. The method was used to quantify sCD14 in different
      biological fluids, giving an intra-assay coefficient of variation and an
      interassay coefficient of variation of about 9%. The assay was used to measure
      sCD14 in human serum and plasma and other body fluids in health and disease, and
      in cell culture supernatants. With the exception of monkeys there was no
      reactivity with 29 other species screened. In healthy volunteers the sCD14 serum
      level had a mean value of 3.98 +/- 0.3 micrograms/ml (mean SEM, n = 102).

PMID- 1385536
TI  - ELISA for quantitation of L-selectin shed from leukocytes in vivo.
AB  - L-selectin is a cell surface receptor on granulocytes, lymphocytes and monocytes
      that is responsible for the initial attachment of leukocytes to endothelium. The
      extracellular domain of L-selectin is proteolytically shed from leukocytes
      following cellular activation in vitro. The shed form of L-selectin (SL-selectin)
      is functionally active and at high concentrations can inhibit leukocyte
      attachment to endothelium. Therefore, an ELISA was developed to quantitate the
      levels of SL-selectin in biological fluids, biopsy specimens and during
      recombinant protein production. This simple, quantitative sandwich ELISA uses two
      monoclonal antibodies directed against the extracellular domain of SL-selectin.
      The assay has a detection range of 5-1300 ng/ml, is precise and sensitive. The
      ability of this assay to detect SL-selectin in serum, plasma, and culture
      supernatant fluid was demonstrated and it was used to quantitate circulating SL
      selectin in normal and patient sera. Patients with sepsis and HIV infection
      showed markedly elevated SL-selectin levels in serum. Thus, the ELISA should
      prove useful both for laboratory purposes as well as in the diagnostic evaluation
      of patients with inflammatory diseases.

PMID- 1385537
TI  - A highly sensitive enzyme-linked immunosorbent assay for the measurement of
      interleukin-8 in biological fluids.
AB  - Interleukin-8 (IL-8) is a chemotactic and activating cytokine for neutrophils,
      which plays an important role in acute inflammatory responses. We aimed to
      develop a sensitive enzyme-linked immunosorbent assay (ELISA) for IL-8 and
      established 18 clones of anti-IL-8 monoclonal antibodies (mAbs). These mAbs were
      evaluated in terms of their antigen-binding affinities, and five clones were
      selected and used for the comparative study of various combinations of antibodies
      in sandwich ELISA. Affinity purified rabbit polyclonal antibody was also used in
      this study. One antibody pair, which showed relatively high sensitivity and which
      was not severely interfered with blood components, was selected and the assay
      conditions were optimized by choosing the appropriate buffer for sample dilution
      and by directly labeling the second antibody with enzyme. The finalized ELISA,
      using polyclonal antibody as first (coated) antibody and horseradish peroxidase
      labeled mAb (clone EL139) Fab' fragment as second antibody, could detect as low
      as 2.5 pg/ml (0.125 pg/well) of IL-8 by in total 2 h incubation, without being
      affected by body fluid components. The ELISA was specific to IL-8, showing no
      cross-reactivity with other cytokines or various IL-8 family proteins which share
      some amino acid sequence homology with IL-8. As an example of its application to
      clinical specimens, plasma samples from patients with septic shock were measured.
      The results showed that sepsis patients contain significantly higher levels of
      plasma IL-8 compared to normal controls. When analyzed by gel-filtration
      chromatography, IL-8 in sepsis plasma was eluted in a molecular weight (M(r)
      region corresponding to the monomer form. The ELISA established here is expected
      to be effectively used for further investigations on the relationship between IL
      8 and various diseases.

PMID- 1385538
TI  - Detection of human leukemia inhibitory factor by monoclonal antibody based ELISA.
AB  - Leukemia inhibitory factor (LIF) is known to exhibit multiple functions by
      regulating the growth and differentiation of multiple normal cell types as well
      as malignant cells. To have a better understanding of the role of LIF, it is
      important to determine the level of LIF in various biological samples by
      developing an easy, sensitive and LIF specific assay. In this study, we have
      established a double monoclonal antibody (mAb) based ELISA. Four hybridoma cell
      lines (D3.14.1, D4.16.9, D25.1.4 and D62.3.2) secreting murine monoclonal
      antibodies (mAbs) against recombinant human leukemia inhibitory factor (rHuLIF)
      were produced by immunization of BALB/c mice with rHuLIF and by fusing immune
      spleen cells with P3X63Ag8U.1 myeloma cells. These mAbs each belong to the IgG1
      isotype and have unique isoelectrofocusing point patterns. All four mAbs were
      shown to have high affinities for rHuLIF (Kd = 7 x 10(-10) to 6 x 10(-11) M) and
      were able to recognize the native as well as the reduced rHuLIF in an
      immunoblotting assay. All these mAbs showed no cross-reactivities to IL-1, IL-3,
      IL-6, TNF-alpha, GCSF and GMCSF. MAb D3.14.1 showed a weak binding to Oncostatin
      M but not to rMuLIF whereas the other three mAbs D4.16.9, D25.1.4 and D62.3.2
      showed cross-reactivity to rMuLIF but not to Oncostatin M. Data obtained from a
      competitive binding enzyme-linked immunosorbent assay (ELISA) suggested that
      these four mAbs recognized different epitopes on rHuLIF. Using mAb D4.16.9 as
      coat antibody and horseradish peroxidase (HRP) conjugated mAb D3.14.1 as the
      conjugate antibody we established a double mAb based ELISA specific for human LIF
      which could detect as little as 100 pg/ml and 10 pg/ml of rHuLIF in the absence
      and in the presence of the ELAST ELISA amplification system, respectively. The
      addition of serum had very minimal effect on this ELISA.

PMID- 1385539
TI  - Homogeneity of lipopolysaccharide antigens in Pseudomonas pseudomallei.
AB  - An antiserum raised against a single strain of Pseudomonas pseudomallei reacted
      equally in a whole cell agglutination test, an indirect haemagglutination (IHA)
      test and an ELISA with a panel of 12 strains of the species which had been
      isolated from human beings and animals in various parts of the Far East and
      Australia between 1923 and 1990. Absorption of the serum with either of two
      strains removed all reactivity of the serum with other strains. Phenol-water
      extracted lipopolysaccharide (LPS) from a single strain blocked the reactivity of
      the serum with red cells sensitised with crude extracts of any of the panel of
      strains, thereby suggesting that the 'common' antigen was LPS. This antigen was
      not detected in other Pseudomonas species with the exception of Pseudomonas
      mallei. Protease K-digested extracts of the 12 strains gave highly similar silver
      stained LPS banding patterns in gel electrophoresis. Furthermore, immunoblots of
      LPS with either rabbit or a patient's serum showed identical ladder profiles for
      each strain. The results suggest that the LPS antigen is highly conserved
      throughout P. pseudomallei and that this antigen is detected by the IHA test.

PMID- 1385540
TI  - IgE-positive Langerhans cells and Th2 allergen-specific T cells in atopic
      dermatitis.
AB  - In atopic dermatitis (AD) IgE-positive Langerhans cells (LC) may be present in
      the epidermis. These LC are able to capture allergens by means of their specific
      IgE, inducing an allergen-specific T-cell response in autologous peripheral blood
      T cells. Epicutaneous patch testing (EPT) may induce an eczematous reaction when
      IgE is present on the LC. Thus, both in vivo and in vitro, it appears that IgE
      may be crucial for induction of allergen-specific T-cell responses. Indeed, the
      cloning of infiltrating T cells from a positive 12-h EPT produced allergen
      specific T cells, wheras no in vivo activated bystander T cells have yet been
      cloned. Moreover, greater than 85% of the T cells cloned were of Th2 phenotype
      after anti-CD3 and phorbol myristate acetate stimulation, whereas all clones were
      Th2 after allergen-specific stimulation, and they were able to induce IgE
      production in normal B cells. This completes the circle of events, because IgE
      produced by peripheral B cells may bind to LC and facilitate new allergen
      specific reactions in the skin.

PMID- 1385541
TI  - Epitope mapping of CD1a, CD1b, and CD1c antigens in human skin: differential
      localization on Langerhans cells, keratinocytes, and basement membrane zone.
AB  - CD1 antigens are classified into at least three groups, CD1a, CD1b, and CD1c. In
      order to delineate the localization of epitopes of CD1 antigens in human skin, we
      examined the immunoreactivity of fourteen different CD1 antibodies (seven CD1a,
      five CD1b, and two CD1c antibodies). The epitopes for CD1a, CD1b, and CD1c are
      differentially localized on epidermal Langerhans cells, dermal dendritic cells,
      keratinocytes, the luminal portion of eccrine gland ducts, and the basement
      membrane zone in normal human skin.

PMID- 1385542
TI  - Early events in the induction phase of contact sensitivity.
AB  - After allergen application to skin, there is enhanced class II major
      histocompatibility complex antigen expression, as well as enhanced T-cell
      stimulatory function by epidermal Langerhans cells (LC). In this study, we
      investigated the early changes in the epidermal cytokine profile using a
      sensitive reverse transcriptase PCR technique to determine whether cytokines may
      be related to LC activation. We found that, on the mRNA and protein level,
      changes in the epidermal cytokine pattern caused by allergens in the induction
      phase of contact sensitivity are distinct from those caused by irritants or
      tolerogens. The earliest of the changes is the LC-derived interleukin (IL) 1 beta
      mRNA signal strength that is increased within 15 min of allergen painting.

PMID- 1385543
TI  - Linkage of the epidermolytic hyperkeratosis phenotype and the region of the type
      II keratin gene cluster on chromosome 12.
AB  - Bullous congenital ichthyosiform erythroderma (epidermolytic hyperkeratosis) is a
      severe, generalized, lifelong disease of the skin. As in epidermolysis bullosa
      simplex, intraepidermal blisters and clumping of keratin intermediate filaments
      are characteristic. We report here linkage of the inheritance of this disease to
      the region of chromosome 12q containing the genes encoding type II keratins. This
      suggests that keratin gene mutations may underlie this complex hyperproliferative
      and hyperkeratotic phenotype.

PMID- 1385544
TI  - Langerhans cells are the major source of mRNA for IL-1 beta and MIP-1 alpha among
      unstimulated mouse epidermal cells.
AB  - Immunocompetent cells of the epidermis can interact by the elaboration and
      recognition of cytokines. Although much new information has been reported
      concerning the cytokines secreted by keratinocytes, little is known about
      cytokines derived from Langerhans cells (LC). To address this deficiency, we
      examined cytokine mRNA profiles in different epidermal preparations from BALB/c
      mice, taking advantage of the sensitive technique of polymerase chain reaction
      (PCR), after reverse transcription of mRNA. In assays of epidermal sheets
      separated from dermis by ammonium thiocyanate, mRNA for IL-1 alpha, IL-1 beta, IL
      6, IL-7, tumor necrosis factor alpha (TNF alpha), TNF beta, granulocyte
      macrophage/colony-stimulating factor (GM-CSF), and macrophage inflammatory
      protein-1 alpha (MIP-1 alpha) were unequivocally present. By contrast, faint
      bands were detected for IL-4, IL-5, and interferon gamma (IFN gamma), and no PCR
      signal was detected for IL-2. Importantly, assays of epidermal cells (EC)
      dissociated with trypsin revealed similar mRNA profiles. To determine the effects
      of cell isolation, fluorescence-activated cell sorter (FACS)-purified Ia- EC were
      first analyzed; all of the previously cited cytokine mRNA were present except for
      IL-1 beta and MIP-1 alpha. EC depleted of LC by a second technique, lysis using
      anti-Ia monoclonal antibody and complement, revealed similar profiles, with
      substantially reduced PCR signals for IL-1 beta and MIP-1 alpha. Finally, FACS
      purified LC (Ia+ EC) clearly expressed IL-1 beta and MIP-1 alpha mRNA, a finding
      that was verified by Southern blotting using internal oligo probes. We conclude
      that these cell-isolation procedures did not produce substantial alterations in
      basal mRNA profiles and that LC are the principal source of mRNA for IL-1 beta
      and MIP-1 alpha among unstimulated EC in mice.

PMID- 1385545
TI  - Functional role of adhesion molecules LFA-3 and ICAM-1 on cultured human
      epidermal Langerhans cells in antigen-specific T-cell activation.
AB  - Interaction of T-cell antigen receptors with antigen/major histocompatibility
      complex (MHC) molecule complexes on antigen-presenting cells (APC) leads to T
      cell activation. Additional interaction between adhesion molecules on the APC and
      their ligands on T cells is required for optimal T-cell activation. In vitro
      cultured human epidermal Langerhans cells (cLC) are powerful APC that express
      adhesion molecules LFA-3 and ICAM-1. Both molecules on cLC serve a functional
      role in the generation of a T-cell response.

PMID- 1385546
TI  - Recovery from cytomegalovirus infection is associated with activation of
      peripheral blood lymphocytes.
AB  - The number of CD8bright and CD56+ lymphocytes in the peripheral blood and their
      activation status were monitored by flow cytometry in 23 renal transplant
      recipients with cytomegalovirus (CMV) infection and were correlated with the
      virus load (as determined by CMV antigenemia) and clinical symptoms. Recovery
      from CMV infection coincided with expansion of the CD8bright and CD56+ subsets
      and with increased expression of the activation marker HLA-DR. Primary infection
      was associated with activation of both subsets, whereas during secondary
      infection, mainly CD8bright cells responded. Progressive CMV disease (requiring
      antiviral treatment) and relapse occurred in association with low numbers of
      activated CD8bright and CD56+ cells. Lymphocyte activation and antibody responses
      against CMV often occurred simultaneously, but different kinetics of these
      responses in some patients indicated that cellular responses are necessary to
      control viral replication, whereas humoral responses alone may be insufficient.
      Monitoring of lymphocyte activation may provide clinically useful information
      during CMV infection.

PMID- 1385547
TI  - Hepatitis C virus is detected in a monocyte/macrophage subpopulation of
      peripheral blood mononuclear cells of infected patients.
AB  - Hepatitis C virus (HCV) is the primary agent of posttransfusion non-A, non-B
      hepatitis. HCV RNA was detected in peripheral blood mononuclear cells (PBMC) by
      polymerase chain reaction in 17 of 24 HCV-infected patients with chronic
      hepatitis with or without cirrhosis. One of 5 patients whose PBMC contained HCV
      RNA also had negative-stranded HCV RNA in the PBMC. In 3 of 11 patients whose
      PBMC contained HCV RNA, flow cytometry with a murine monoclonal antibody to HCV
      core epitope revealed cytoplasmic staining of peripheral blood monocytes. The
      monocyte surface and the peripheral blood lymphocytes did not stain for HCV core
      epitopes. No correlation could be made between the presence of HCV RNA or antigen
      in PBMC and any serologic markers of HCV infection. These results indicate that
      monocyte uptake of HCV by either phagocytosis or infection may be part of the
      pathophysiology of this chronic disease.

PMID- 1385548
TI  - Human monoclonal antibodies against an epitope on the class 5c outer membrane
      protein common to many pathogenic strains of Neisseria meningitidis.
AB  - Neisseria meningitidis is a causative agent of meningitis. Despite vaccination
      programs, it still causes a large number of deaths in young children. Early
      diagnosis followed by passive immunization with human monoclonal antibodies could
      be an approach to effective therapy. Peripheral blood lymphocytes from normal,
      healthy blood donors and from vaccinated individuals were immunized in vitro,
      using outer membrane proteins purified from N. meningitidis B:4:P1.15. The
      immunized human B cells were Epstein-Barr virus transformed and fused to a
      heteromyeloma. Several stable human hybridoma cell lines were established and
      two, secreting antibodies against the 31-kDa class 5c outer membrane protein,
      were characterized further. The human antibodies were of IgG1 and IgG3 isotypes,
      with kappa light chains. The recognized epitope was commonly found among
      pathogenic strains of N. meningitidis; thus, these human monoclonal antibodies
      may be important in the evaluation of N. meningitidis infections.

PMID- 1385550
TI  - Identification of the Rochalimaea henselae 16S rRNA sequence in the liver of a
      French patient with bacillary peliosis hepatis.

PMID- 1385549
TI  - Binding of plasminogen to Neisseria meningitidis and Neisseria gonorrhoeae and
      formation of surface-associated plasmin.
AB  - Forty-two strains of Neisseria meningitidis and 17 of Neisseria gonorrhoeae were
      tested for their ability to interact with 125I-labeled Glu-plasminogen. All
      strains tested reacted substantially with plasminogen, resulting in uptake values
      of 20%-48%. Scatchard analysis with selected N. meningitidis strains demonstrated
      a dual-phase receptor interaction, one more avid receptor with a Kd of 50 nM and
      3000-6000 receptors per bacterium and a second receptor with a Kd of 200 nM and
      10,000-20,000 receptors per bacterium. Plasminogen uptake could be completely
      eliminated by low concentrations of epsilon-aminocaproic acid, suggesting that
      the lysine binding sites on the plasminogen molecule are involved in the receptor
      ligand interaction. The binding of plasminogen to the bacterial receptor
      facilitates the tissue-type plasminogen activator-mediated conversion to Glu
      plasmin, which also modifies itself to the Lys form. Receptor-associated plasmin
      is enzymatically active, monitored as a breakdown of the chromogenic substrate S
      2251, and retains its activity in the presence of naturally occurring inhibitors
      in plasma.

PMID- 1385551
TI  - The antiviral effects of the interferons and their inhibition.

PMID- 1385552
TI  - The war against the interferon-induced dsRNA-activated protein kinase: can
      viruses win?

PMID- 1385553
TI  - The interferons, macrophage activation, and host defense against nonviral
      pathogens.

PMID- 1385554
TI  - [Clinical studies on maternal serum alpha-fetoprotein (MSAFP) of 532 cases--the
      median value, pregnancy outcomes and clinical evaluation].
AB  - MSAFP screening program has gradually become widespread. Prenatal diagnosis of
      fetal anomalies by means of the MSAFP level has become increasingly integrated
      into the routine components of obstetric management. During the period from June,
      1990 through January, 1991, 516 pregnant women between 12 and 19 weeks' gestation
      participated in MSAFP screening and there were 532 MSAFP cases including repeat
      16 cases for which follow-up data have been completed. 1. Of this population, 5
      cases (0.9%) had increased MSAFP (> or = 2.5MOM). One case was IUFD, one case was
      twin, one case was Breus' mole, two cases had normal repeat MSAFP levels. Thirty
      three cases (6.2%) had low MSAFP (0.5 < or = MOM). One abnormal karyotype
      (46,XY,16p+) was discovered among twenty-six cases by undergoing amniocentesis
      (3.8%). 2. Of the four hundred ninety-four cases (92.8%) with a normal MSAFP
      level, thirty-three (6.9%) had an adverse pregnant outcome. Eight cases were
      prematurity, eight cases were low birth weight infants, six cases were large-for
      date infants, two cases were IUFD, one case was Klinefelter's syndrome, one case
      had cystic hygroma and one case was had a tracheo-esophageal fistula. 3. A woman
      with an extremely high MSAFP level, with normal ultrasonography and with normal
      amniocentesis results should be regarded as a high-risk pregnancy and need
      further close follow-up to detect placental abnormalities.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1385555
TI  - The role of myosin phosphorylation in RBL-2H3 cell secretion.

PMID- 1385557
TI  - Evidence for the involvement of tyrosine kinases in the locomotory responses of
      human neutrophils.
AB  - Erbstatin, a recently described inhibitor of tyrosine kinases, has been used to
      examine the potential role of tyrosine phosphorylation in human neutrophil
      locomotion. Preincubation of human neutrophils with erbstatin inhibited both
      spontaneous and directed migration induced by chemotactic factors such as
      formylmethionylleucylphenylalanine (fMet-Leu-Phe) and leukotriene B4. The
      decreased migratory responses were correlated with an inhibition of adherence of
      neutrophils to serum-coated surfaces. Erbstatin did not, however, affect the
      adherence of human neutrophils to uncoated surfaces. These results indicated that
      the inhibitory effects of erbstatin were specific and not due to a generalized
      alteration of the surface of human neutrophils. To elucidate the mechanism of the
      inhibitory effect of erbstatin on adherence properties, the expression of the
      leukocyte integrin Mo1 was studied. Erbstatin induced a small but significant
      increase in the expression of Mo1, but decreased the stimulation of the
      expression of Mo1 elicited by fMet-Leu-Phe. These results suggest that mechanisms
      in addition to alteration of the number of surface integrins are involved in the
      inhibition of neutrophil adherence and locomotion by erbstatin.

PMID- 1385556
TI  - Marked increase in plasma interleukin-6 in burn patients.
AB  - We measured the levels of interleukin-6 in plasma samples from 18 consecutive
      burn patients, including three lethal cases, during the early postburn period. In
      survivors burn injury caused initial increases in interleukin-6 levels that
      peaked at 6 hours after burn; this was significantly higher than interleukin-6
      levels in normal controls (718 +/- 216 vs 70 +/- 4 pg/ml; p < 0.01). The
      increment in nonsurvivors was even more prominent (11,554 +/- 4,407 pg/ml; p <
      0.01). The peak interleukin-6 levels at 6 hours correlated with total burn
      surface area (r = 0.65, p < 0.025), and tended to be higher in patients with
      inhalation injury. These data provide evidence that burn injury causes rapid
      release of interleukin-6 according to the severity of the injury. We also
      measured acute-phase reactants including fibrinogen, alpha 1-antitrypsin, C1
      inhibitor, and alpha 2-plasmin inhibitor. After initial declines, these four
      proteins increased rapidly in survivors. In addition, the peak interleukin-6
      levels correlated well with the increases in fibrinogen (p < 0.025), alpha 1
      antitrypsin (p < 0.01), C1 inhibitor (p < 0.01), and alpha 2-plasmin inhibitor (p
      < 0.0001). In contrast, despite the marked increase in interleukin-6, the levels
      of acute phase proteins in nonsurvivors remained low. Based on these
      observations, we suggest that interleukin-6 is released as an alarm signal and
      has a role for the wound healing in burn patients, and that the levels of
      interleukin-6 after injury is an indicator of the severity of burn.

PMID- 1385558
TI  - Functional alterations of swine peripheral blood mononuclear cells by methadone.
AB  - In vitro exposure of the synthetic opiate drug methadone allowed evaluation of
      putative immunomodulatory activities of swine peripheral blood mononuclear cells.
      Respiratory burst, an index of microbicidal activity, was suppressed by methadone
      in a dose-dependent manner following exposure for 48 h. The suppression was
      blocked by the opiate antagonist naloxone. Another macrophage function phagosome
      lysosome fusion was impaired by exposure to methadone. A primary lymphocyte
      mediated function natural killer cell activity was also affected. In contrast,
      the macrophage function antibody-mediated phagocytosis was not affected. Because
      the functions affected by methadone are critical to host defenses against
      pathogenic organisms, our findings suggest that opiate-mediated immunomodulation
      merits further study. Moreover, our studies suggest that swine may provide an
      ideal model for the investigation of opiate-mediated suppression of immune cell
      functions.

PMID- 1385559
TI  - Interleukin-2 signal transduction in human NK cells: multisite phosphorylation
      and activation of the tyrosine kinase p56lck.
AB  - Interleukin-2 (IL-2) potently stimulates natural killer (NK) cell proliferation
      and cytotoxic function. However, the molecular mechanisms by which IL-2 delivers
      activation signals from the IL-2 receptor to the NK cell interior are
      incompletely understood. Previous studies demonstrated that IL-2 stimulation
      induced the tyrosine phosphorylation of multiple proteins in NK cells, together
      with a prominent reduction in the electrophoretic mobility of p56lck. The present
      studies indicate that IL-2 induces a rapid (< or = 1 min) increase in the
      catalytic activity of p56lck, as measured by increases in protein tyrosine kinase
      activity in vitro. Furthermore, in response to IL-2, p56lck itself undergoes
      complex alterations in serine and tyrosine phosphorylation. Cyanogen bromide
      cleavage maps indicate that IL-2 stimulates a pronounced increase in the
      phosphorylation of the NH2-terminal region of p56lck containing multiple known
      sites of serine phosphorylation. In addition, IL-2 induced a marked increase in
      the phosphorylation of a COOH-terminal peptide containing the regulatory Tyr-505
      residue of p56lck. These results suggest that p56lck serves as a substrate for
      both protein serine and tyrosine kinases activated during stimulation of this
      cell type with IL-2. Furthermore, these results indicate that the pleiotropic
      effects of IL-2 on NK cell physiology are initiated and regulated by a complex
      and multitiered interaction of different protein kinases including p56lck.

PMID- 1385560
TI  - Epitope mapping of the human biliary amphipathic, anionic polypeptide: similarity
      with a calcium-binding protein isolated from gallstones and bile, and immunologic
      cross-reactivity with apolipoprotein A-I.
AB  - Biliary amphipathic anionic polypeptide (APF) the major protein of the pigment
      lipoprotein complex in bile, and calcium-binding protein (CBP) from gallstones
      are both small (less than 10 kDa), highly acidic, amphipathic proteins present in
      bile and closely associated also with pigmented areas in human gallstones.
      Polyclonal antibodies against APF have shown cross-reactivity with plasma high
      density lipoproteins (HDL). This study examines the hypothesis that APF and CBP
      might be closely related or even identical, and might also share common epitopes
      with the larger apoA-I (23 kDa). To assess this, immunoreactivity of the three
      delipidated, highly purified proteins was determined against a panel of 12
      monoclonal antibodies (MAbs) prepared against APF and a panel of 4 MAbs against
      apoA-I. APF was isolated from bile by zonal ultracentrifugation. CBP was isolated
      from proteins precipitated from bile by CaCl2, as well as from the calcium
      bilirubinate shells of cholesterol gallstones, by extraction successively with
      methyl-t-butyl ether, methanol, and Na2EDTA, followed by Sephadex G-25
      chromatography and two-stage preparative SDS-PAGE. ApoA-I was prepared by two
      types of chromatography: Sephacryl S200 chromatography and heparin
      chromatographic immunoaffinity. Specific polyclonal antibodies to APF and apoA-I
      were prepared from immunized rabbits. MAbs to APF and apoA-I were prepared by
      immunization of mice, using standard hybridoma technique. Western blotting of APF
      and CBP in 15% SDS-PAGE yielded one band with an apparent molecular weight of 6.5
      kDa, which, along with apoA-I, was immunostained by polyclonal antibodies to APF
      and apoA-I. Using 12 MAbs against APF with three types of ELISA (direct antigen
      binding, competitive antigen displacement, and epitope competition between
      antibodies), it was shown that APF and delipidated apoA-I shared six epitopes,
      three of which were detected also on the surface of intact HDL particles. Six
      other epitopes were present in APF but not apoA-I, four of which were exposed on
      the surface of HDL. Four MAbs against apoA-I reacted with APF and CBP. Amino acid
      analyses of APF and CBP were similar with 20-23% acidic and 7-11% basic amino
      acids and low contents of cysteine, methionine, and tyrosine; both differed from
      apoA-I in containing isoleucine and cysteine. Using ELISA and one MAb (no. 32)
      against APF, this polypeptide was detected in human plasma HDL, the pigment
      lipoprotein complex in the bile of humans, dogs, and rats, and in both pigment
      and cholesterol gallstones.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1385561
TI  - Phytanic acid alpha-oxidation: accumulation of 2-hydroxyphytanic acid and absence
      of 2-oxophytanic acid in plasma from patients with peroxisomal disorders.
AB  - A stable isotope dilution method was developed for the measurement of 2
      hydroxyphytanic acid and 2-oxophytanic acid in plasma. In plasma from healthy
      individuals and from patients with Refsum's disease, 2-hydroxyphytanic acid was
      found at levels less than 0.2 mumol/l, whereas the acid accumulated in plasma
      from patients with rhizomelic chondrodysplasia punctata, generalized peroxisomal
      dysfunction, and a single peroxisomal beta-oxidation enzyme deficiency. In plasma
      from both healthy controls and patients with peroxisomal disorders, 2-oxophytanic
      acid was undetectable. Four different groups of diseases were characterized with
      a defective phytanic acid alpha-oxidation and/or pristanic acid beta-oxidation:
      1) Refsum's disease, with a defect at phytanic acid alpha-hydroxylation; 2)
      rhizomelic chondrodysplasia punctata, with a defect at 2-hydroxyphytanic acid
      decarboxylation; 3) generalized peroxisomal disorders, with defects at 2
      hydroxyphytanic acid decarboxylation and at pristanic acid beta-oxidation; 4)
      single peroxisomal beta-oxidation enzyme deficiencies, with a defect at pristanic
      acid beta-oxidation, resulting in an impaired phytanic acid alpha-oxidation by
      inhibition. The results indicate that 2-hydroxyphytanic acid decarboxylation and
      pristanic acid beta-oxidation take place in peroxisomes.

PMID- 1385562
TI  - Two-year follow-up after laser thermal balloon angioplasty (LTBA) in lower
      extremities: initial experience.
AB  - We describe the results obtained with the use of laser thermal balloon
      angioplasty (LTBA) in the treatment of atherosclerosis obliterans of the lower
      limbs in 37 patients (34 males, 3 females, mean age 58 +/- 9 years) with
      occlusive arterial disease (Fontaine stages II-IV) presenting 39 significant
      lesions. Immediate results and two years of clinical follow-up are analyzed.
      Initial ankle/brachial Doppler index was 0.51 +/- 0.17. Eighteen lesions were
      located in the iliac area (13 stenoses 2.3 +/- 1 cm and 5 occlusions 4.2 +/- 3
      cm) and 21 lesions in the femoropopliteal area (5 stenoses 2.6 +/- 2 cm and 16
      occlusions 5.7 +/- 3 cm). A percutaneous procedure was used in 38 cases. In only
      one case was femoral dissection needed. The laser source was argon in 26 cases
      and Nd-YAG in 13. Initial success was 85% (89% in iliac lesions and 81% in
      femoropopliteal lesions; 100% in stenoses and 70% in occlusions). The presence of
      occlusion (p less than 0.01) and/or calcium (p less than 0.05) negatively
      influenced the immediate results. No major complications were observed; seven
      (17%) minor complications occurred. Ankle/brachial Doppler index after treatment
      was 0.82 +/- 0.21. Cumulative clinical patency for successfully treated patients
      after two-year follow-up was 91%. LTBA thus represents an effective and less
      aggressive way of treating peripheral atherosclerosis obliterans. In spite of
      some limitations, it is useful in selected patients. The results of this study
      are very much like those in the literature for similar series and early
      experience.

PMID- 1385564
TI  - The effect of the plasma levels of proteins C and S on the prediction of warfarin
      maintenance dose requirements.
AB  - OBJECTIVE: Determination of the effects of the vitamin K-dependent
      anticoagulants, proteins C and S, on warfarin dose requirements and on the
      prediction error of a bayesian warfarin dose predicting program. METHODS:
      Patients in the study were consecutive inpatients (n = 18) starting treatment
      with warfarin who were monitored as outpatients for 4 weeks. The following
      measurements were taken: repeated (n = 8) prothrombin times, expressed as the
      international normalized ratio (INR), plasma protein C and S antigen levels
      (percentage of pooled normal plasma), demographic, clinical and biochemical
      variables. RESULTS: Maintenance doses (adjusted to INR 2.5) were 6.7 +/- 3.4
      mg/day. Protein C decreased to 56.9% +/- 15.3%, protein S to 63.7% +/- 17.3%, INR
      increased to 2.46 +/- 0.14. Prediction error decreased from 2.84 +/- 2.0 mg/day
      to 0.95 +/- 0.78 mg/day. Protein C accounted for only 4.2% of the mean
      maintenance dose but protein C and S levels accounted for 31% of the mean dose
      prediction error. CONCLUSION: Protein C and S levels affect warfarin doses and
      predictions significantly but not to a clinically meaningful degree.

PMID- 1385563
TI  - Atrial natriuretic factor in essential hypertension: echocardiographic and
      humoral correlates.
AB  - Aim of this study was to assess the relationship between plasma concentration of
      atrial natriuretic factor (ANF) and its two-dimensional echocardiographic (left
      ventricular mass, left atrium diameter) and humoral (plasma renin and
      aldosterone) variables in essential hypertension (EH). We evaluated 32 patients
      with uncomplicated mild to moderate EH and 10 controls. They were studied in the
      supine position after 7 days of constant dietary sodium intake and were off
      therapy since at least 3 weeks. ANF values overlapped between EH patients and
      controls (27.8 +/- 11.5 vs. 19.5 +/- 7.4 pg/ml, p = NS). In EH, no significant
      correlation was found between ANF values and left ventricular mass (r = 0.29),
      left atrial diameter (r = 0.04), mean arterial blood pressure (r = 0.26), plasma
      renin activity (r = 0.00), and aldosterone (r = 0.26). In EH, ANF values
      overlapped between the 15 patients with hypertrophy and the 17 patients with
      normal ventricular mass: 30.3 +/- 17 vs. 25.6 +/- 10.6 pg/ms (p = NS). We
      conclude that there is a substantial overlap in plasma ANF values between mild to
      moderate uncomplicated EH and controls, and left ventricular hypertrophy is not a
      major independent stimulus to ANF release in EH.

PMID- 1385565
TI  - Antihypertensive mechanism of amlodipine in essential hypertension: role of
      pressor reactivity to norepinephrine and angiotensin II.
AB  - Calcium entry blockade may affect the pressor reactivity to vasoconstrictors. The
      pressor response to norepinephrine and angiotensin II, as well as several other
      blood pressure modulating factors, were studied in normal subjects (n = 9) and
      patients with essential hypertension (n = 10) before and after 8 weeks of
      treatment with the long-acting dihydropyridine amlodipine. In control subjects,
      calcium entry blockade did not modify blood pressure, the pressor and aldosterone
      response to angiotensin II, the activity of the renin-angiotensin and sympathetic
      nervous systems, or urinary dinoprostone (prostaglandin E2) excretion; however,
      the pressor response to norepinephrine was significantly decreased (p less than
      0.01). In patients with hypertension, amlodipine decreased blood pressure (p less
      than 0.01) and the pressor response to both norepinephrine and angiotensin II (p
      less than 0.01), without changes in body weight, plasma renin, angiotensin II and
      catecholamine levels, dinoprostone excretion, or aldosterone responsiveness to
      angiotensin II. These findings suggest that calcium entry blockade modifies
      sympathetic-dependent vasoconstriction in both normal subjects and in patients
      with hypertension. Angiotensin II pressor response may be selectively decreased
      in essential hypertension.

PMID- 1385566
TI  - Plasma concentration--effect relationships for felodipine: a meta analysis.
AB  - The plasma concentration versus antihypertensive effect relationship for the
      calcium antagonist felodipine was investigated in 67 patients with hypertension
      and 21 healthy subjects by use of the Emax model. No consistent effect of
      felodipine on blood pressure was observed in the healthy subjects. In patients
      with hypertension the plasma drug concentration and blood pressure versus time
      curves mirrored each other, indicating a close relationship between concentration
      and effect. The maximum effect (Emax) model fitted the diastolic blood pressure
      data of most patients, but the model was less often applicable in patients with
      low initial diastolic blood pressure levels. The average Emax values and the
      plasma felodipine concentration needed to obtain 50% of Emax for the patients
      with hypertension were 29 mm Hg and 8 nmol/L, respectively. The Emax values
      increased with increasing initial diastolic blood pressure levels but were
      similar in patients with high and low plasma felodipine concentrations. Age had
      negligible influence on the antihypertensive response to felodipine when
      compensation was made for the plasma concentrations.

PMID- 1385567
TI  - Ondansetron is effective in decreasing postoperative nausea and vomiting.
AB  - The efficacy of ondansetron, a selective 5-HT3 receptor antagonist, in preventing
      postoperative nausea and vomiting in surgical patients was studied. Fifty women
      were randomized in a double-blind manner to receive either two 8 mg doses of
      intravenous ondansetron or two doses of placebo vehicle: the first given just
      before general anesthesia induction and the second 8 hours later. During the
      first 24 postoperative hours, the number of emetic episodes was recorded and the
      subjects rated their nausea on a scale from 0 to 10. Ondansetron-treated subjects
      had fewer emetic episodes (p less than 0.001) and lower subjective nausea scores
      (p less than 0.001). The number of complete responders (no emetic episodes and no
      rescue therapy) was 1 of 24 (4%) and 15 of 26 (58%) in the placebo and
      ondansetron groups, respectively (p less than 0.001). Ondansetron is clearly more
      effective than placebo in the prophylaxis of postoperative nausea and vomiting.
      The adverse event profile for ondansetron was similar to that of placebo.

PMID- 1385568
TI  - HIV and disability.

PMID- 1385569
TI  - Increased capillary permeability for plasma proteins in oral contraceptive users.
AB  - The transcapillary fluid balance was examined in eleven women before
      administration of a monophasic oral contraceptive (desogestrel 0.15 mg,
      ethinylestradiol 0.03 mg), and after three and six months of use. The
      interstitial colloid osmotic pressure was measured by the "wick" method, and the
      interstitial hydrostatic pressure by the "wick-in-needle" method in subcutaneous
      tissue on thorax and leg. During the six-month observation period, the following
      changes were observed: Plasma colloid osmotic pressure decreased (mean 1.8 mmHg,
      p = 0.047), as well as serum albumin (mean 5.1 g/l, p = 0.0006), total protein
      concentration (mean 2.8 g/l, p = 0.0006), hemoglobin (mean 0.5 g/dl, p = 0.014)
      and hematocrit (mean 1.8%, p = 0.047). Blood pressure and body weight remained
      unchanged, but foot volume showed a significant increase. The colloid osmotic
      pressure gradient (plasma-interstitium) was significantly reduced. The results
      indicate an increase in plasma volume in addition to an increased capillary
      permeability to plasma proteins during oral contraceptive use. We suggest that
      the observed changes in transcapillary fluid balance is caused by the estrogen
      component of the oral contraceptive pill.

PMID- 1385570
TI  - Increased proportions of peripheral blood gamma delta T cells in patients with
      pulmonary tuberculosis.
AB  - There is a small population of peripheral T cells bearing the gamma delta T-cell
      receptor, which may be involved in the defense against invading microorganisms
      and tumor cells. The present study was designed to evaluate the levels of gamma
      delta T cells in patients with pulmonary tuberculosis, bacterial pneumonia,
      chronic lower respiratory tract infection, lung cancer, and normal control
      subjects with or without old tuberculous lesion. The results showed that only
      patients with tuberculosis had significantly increased proportions of peripheral
      blood gamma delta T cells. This study suggests that the increased proportions of
      gamma delta T cells in tuberculosis could be related to T-cell activation by
      Mycobacterium tuberculosis, although it remains to be investigated which
      components of mycobacteria are the major ligands for gamma delta T cells.

PMID- 1385571
TI  - Whither goest the right ventricle in obstructive sleep apnea?

PMID- 1385572
TI  - Physical activity, physical fitness, and low back pain.

PMID- 1385573
TI  - Secretion of granulocyte-macrophage colony-stimulating factor by human blood
      monocytes is stimulated by engagement of Fc gamma receptors type I by solid-phase
      immunoglobulins requiring high-affinity Fc-Fc gamma receptor type I interactions.
AB  - Despite reports on the secretion of granulocyte-macrophage-colony-stimulating
      factor (GM-CSF) by murine peritoneal macrophages in response to inflammatory
      stimuli, the ability of human monocytes to generate this growth factor has
      remained doubtful. Neither endotoxin, phorbol compounds, nor inflammatory
      cytokines have been shown to elicit GM-CSF by these cells. Our present studies
      indicate that exposure of monocytes to solid-phase murine IgG2a, but not to
      murine IgG1 and thus cross-linkage of the 72-kDa Fc gamma RI results in
      transcription of the GM-CSF gene, accumulation of stable GM-CSF mRNA and finally
      in release of biologically active GM-CSF protein. Cross-linking of Fc gamma RI by
      a murine anti-Fc gamma RI monoclonal antibody and goat anti-mouse antibody
      failed, however, to stimulate GM-CSF release. This suggests that high affinity Fc
      Fc gamma RI interactions are required for induction of expression of GM-CSF by
      monocytes.

PMID- 1385574
TI  - Inhibition of abnormal T cell development and autoimmunity in gld mice by
      transgenic T cell receptor beta chain.
AB  - Mice homozygous for the gld (generalized lymphoproliferative disease) mutation
      developed systemic autoimmune disease and severe lymphadenopathy due to an age
      related accumulation in the peripheral lymphoid organs of polyclonal T cells
      bearing a unique phenotype (CD4-CD8-TCR alpha beta+B220+). These T cells
      overexpress T cell receptor (TcR) alpha beta chain RNA, proto-oncogenes c-myb and
      fyn, and proliferate poorly in response to TcR-mediated stimulation. The origin
      of these T cells is poorly understood. To study the influence of a functionally
      rearranged TcR beta chain on the T cell developmental abnormality of the gld
      mutation and autoimmunity, we have backcrossed TcR V beta 8.1-transgenic mice to
      C3H-gld/gld to homozygosity (transgenic gld mice). In transgenic gld mice,
      lymphadenopathy was markedly inhibited and the accumulation of CD4-CD8- T cells
      did not occur, although the remaining T cells overexpressed c-myb and
      proliferated poorly in response to TcR occupancy. These features indicate that
      the pattern of proto-oncogene expression and abnormal function persist in
      phenotypically normal T cells in transgenic gld mice, and that these
      characteristics can be dissociated from the accumulation of CD4-CD8- T cells. The
      hypergammaglobulinemia and anti-double-stranded DNA (anti-dsDNA) antibody
      production was partially improved in transgenic gld mice, supporting the critical
      role of T cells in abnormal B cell activation described in autoimmunity-prone
      mice. To investigate further the mechanisms underlying the inhibition of CD4-CD8-
      T cell accumulation in transgenic gld mice, the fetal ontogeny of T cells in
      transgenic mice was compared with that of non-transgenic mice. In transgenic
      thymus, development of TcR alpha beta+ cells was accelerated as detected by
      earlier expression of CD4, CD8 and TcR in fetal thymus. In contrast, the number
      of TcR gamma delta+ cells was reduced. We suggest that altered T cell development
      in transgenic mice directly or indirectly inhibits the accumulation of abnormal T
      cells in gld mice.

PMID- 1385575
TI  - Selection of murine T cell receptor alpha beta and gamma delta cells in organ
      cultures established from 14-day embryos.
AB  - The expression of minor lymphocyte stimulatory locus (Mls) determinants in
      combination with murine major histocompatibility complex (MHC) class II
      molecules, leads to the destruction of lymphocytes bearing specific V region
      encoded T cell receptor (TcR) products. A much studied example is the elimination
      of V beta 6+ cells in IE+/Mls-1a mice, in which deletion can be detected 7-10
      days after birth but is not fully operational earlier in embryonic life. Here we
      investigate this transitional period in development and show that selective
      deletion of V beta 6 occurs in vitro, approximately 1 week after organ cultures
      are established from 14 day embryos. These unmanipulated organ cultures receive
      no additional cell immigrants after day 14, suggesting that the cellular elements
      mediating negative selection (or their direct precursors), are already resident
      in the fetal thymus by day 14 of gestation. Hence, the developmental timing of
      the outset of rigorous negative selection of V beta 6 is not dictated by the
      postnatal entry of deleting elements into the thymus, but perhaps by the
      maturation of the pre-existing environment. Using a parallel organ-culture
      approach we have looked at the development of V delta 4 and V gamma 3, TcR gamma
      delta+ cells in a variety of mouse strains. These receptors have recently been
      reported to be subject of MHC and non-MHC linked selection, respectively. We find
      that after an initial period of expansion, the number of V gamma 3-expressing
      cells dramatically declines. However, this selective loss of V gamma 3 cells is
      not contingent on the C57BL/6 mouse strain (in contrast to a previous report).
      These findings are discussed in the context of current models of ontogeny and
      repertoire selection.

PMID- 1385576
TI  - Specificity of rat T cell receptor V beta chain usage in proliferative responses
      to staphylococcal enterotoxin B.
AB  - The staphylococcal enterotoxins (SE) are potent stimulators of T cell
      proliferative responses in humans and in mice. In these systems, the toxins
      function as superantigens and stimulate T cells bearing particular V beta.
      Although homology between the V beta of mice and humans is limited, related V
      beta families may respond to certain SE in a similar fashion. In this report, we
      have characterized the rat T cell response to staphylococcal enterotoxin B (SEB).
      Rat T cells from several lymphoid organs proliferated strongly in response to
      both commercially available and recombinant SEB. Using a polymerase chain
      reaction assay, we identified the predominant V beta families stimulated by this
      enterotoxin. The T cell receptor V beta elements used by rat T cells were similar
      to but not completely identical with those used by mice. The V beta profile
      stimulated depended on the purity of the SEB preparation used.

PMID- 1385577
TI  - Bone marrow cells of athymic nude mice express functional T cell receptor alpha
      chain transcripts rearranged to V delta 2, 3, 4, 5, 6 genes.
AB  - From bone marrow cells (BMC) of athymic nude mice, T cell receptor (TcR) alpha
      chain transcripts were selectively amplified by polymerase chain reaction (PCR)
      using V delta 2-, V delta 3-, V delta 4-, V delta 5-, V delta 6- and C alpha
      specific primers. Amplified DNA fragments were cloned, and 32 randomly selected
      clones from 5 PCR were sequenced. Twenty-three distinct rearrangement events were
      detected, of which 87% (20/23) were in-frame. All five tested V delta genes (V
      delta 2, 3, 4, 5, 6) rearranged in-frame to J alpha-C alpha. N-region diversity
      in V delta-J alpha junctions present in most clones was limited to two to five
      nucleotides. P-nucleotide additions in this region were also detected. The V
      delta 5 gene located 3' of C delta in reversed transcriptional orientation was
      rearranged to J alpha by inversion. The J alpha usage pattern of the sequenced
      clones was strongly biased towards rearrangement of the most 5' genes (located
      nearest to C delta) of the J alpha cluster: the most 5' J alpha (J alpha TA1) was
      used by 30% of all clones, and 78% of all J alpha rearranged to V delta were
      located in the 5' 12 kb of the 60-kb J alpha cluster. As distinct V delta/C delta
      and V alpha/C alpha TcR usage patterns are prevalent in peripheral T cell
      populations, our data suggest that these TcR usage patterns results from
      repertoire selections operating in alpha beta and gamma delta T cell lineages,
      but not from preferential V delta-C delta and V alpha-C alpha rearrangement
      patterns.

PMID- 1385578
TI  - Ti gamma A + delta TCS1+ T cells in human thymus. Analysis of the T cell
      receptor.
AB  - TcR1+ T cells in peripheral blood have been shown to express in an exclusive
      fashion either the Ti gamma A or the delta TCS1 epitope. Here, we characterize a
      subset of TcR1+ T cells in fresh thymus co-expressing the Ti gamma A and delta
      TCS1 epitopes. TcR1dim and TcR1bright clones can be distinguished. Biochemical
      and molecular studies on both types of clones generated from these thymocytes
      reveal a unique T cell receptor structure characterized by the use of a V gamma
      9/C gamma 2-encoded 55-kDa gamma chain nondisulfide linked to a V delta 1-encoded
      delta chain.

PMID- 1385579
TI  - Expression of opsin and IRBP genes in mutant RCS rats.
AB  - The retinal pigment epithelium of RCS rats bearing the autosomal recessive rdy
      mutation fails to ingest shed rod outer segment tips. Accumulation of disk debris
      in the subretinal space of the maturing mutant retina causes a secondary
      degeneration of photoreceptor cells. Two hypotheses have been offered as possible
      explanations of the death of photoreceptor cells in this disorder: (1)
      photoreceptors are starved for amino acids, retinal, oxygen, etc; and (2) that
      IRBP levels and synthesis may be decreased and interfere with retinal transport
      and this deficiency is lethal to these cells. To test these hypotheses, we have
      studied the effect of this mutation on the levels of expression of opsin and IRBP
      genes, and gene products and on rates of synthesis at various ages in dystrophic
      RCS p+ rats and compared the results to those obtained with normal Long Evans
      rats. The mutant rats and normal controls had comparable amounts of opsin and
      IRBP mRNA transcripts and rates of synthesis up to post-natal day 45 (P45) but
      opsin transcripts were barely detectable at P60 and thereafter. IRBP mRNA levels
      were also very low after P62 although somewhat higher than opsin mRNA. Opsin
      could be detected immunochemically, albeit at lower levels, at all the ages
      studied up to P310, but IRBP levels fell below detection after P45. We localized
      opsin and IRBP in the retina by post-embedding EM immunocytochemical procedures
      and found that opsin is present in the remnants of rod outer segment debris, even
      at P390, long after detectable opsin synthesis had ceased. These data suggest
      that expression of opsin and IRBP genes is not influenced by the shape and state
      of the outer segments, and that the rdy mutation does not influence the
      expression of the opsin and IRBP in these retinas until the photoreceptor cells
      are profoundly damaged. Thus, neither hypothesis about the causes of cell death
      in this disorder is supported.

PMID- 1385581
TI  - Involvement of lipocortin I in development of galactose-induced cataracts in rat.

PMID- 1385582
TI  - Changes in T-cell regulation of responses to self antigens in women with pelvic
      endometriosis.
AB  - OBJECTIVE: To study autoimmune aspects of endometriosis. DESIGN: Lymphoblast
      transformation and hemolytic plaque formation were used to assess specific T- and
      B-cell activity against endometrial antigens. SETTING: Military teaching
      hospital. PATIENTS: Ninety-four healthy women of reproductive age undergoing
      diagnostic laparoscopy as part of an evaluation for infertility or chronic
      pelvalgia were accordingly grouped into those with normal pelvic peritoneum (20),
      mild endometriosis (50), and severe endometriosis (24). MAIN OUTCOME MEASURE: The
      study assessed the proliferative and humoral responses of lymphocytes from women
      with and without endometriosis to endometrial antigens and quantified the number
      of B-cell precursors, T-helper cells, and T-suppressor cells to these antigens.
      RESULTS: Unfractionated endometrial antigens were similarly blastogenic for
      lymphocytes from women with and without endometriosis. Despite equivalent numbers
      of B-cell precursors to these antigens, antiendometrial antibody responsiveness
      appears to have increased in women with mild endometriosis because of a decrease
      in T-suppressor cell activity and declined in women with severe endometriosis
      because of a further drop in T-suppressor cell activity and an increase in T
      helper cell activity, as compared with women without endometriosis. CONCLUSIONS:
      Taken together, these experiments support the possibility that pelvic
      endometriosis may result from a break in specific T-cell tolerance rather than
      nonspecific polyclonal activation of responder lymphocytes.

PMID- 1385580
TI  - RPE conditioned medium stimulates photoreceptor cell survival, neurite outgrowth
      and differentiation in vitro.
AB  - In the present study we have investigated retinal pigment epithelium
      photoreceptor cell interactions in vitro, and their contributions to
      photoreceptor cell survival and differentiation. Preparations enriched for intact
      photoreceptor cells from neonatal rat retina were grown in either serum-free
      medium supplemented with RPE-conditioned medium (RPE-CM) or in serum-free medium
      alone. A variety of substrate conditions were tested for the best neurite
      outgrowth. Cultures were monitored for 7 days by light and electron microscopy,
      as well as by opsin, vimentin and carbonic anhydrase-C immunocytochemistry. RPE
      CM was found to stimulate both proliferation of flat cells and photoreceptor
      differentiation. The number of photoreceptors bearing neurites and their neurite
      length measurements showed significant differences between the RPE-CM group and
      the control group within 20 hr in culture. Elimination of contaminating flat
      cells by the addition of an antimitotic drug prevented photoreceptor cell
      morphological maturation; however, these cells survived as round cell bodies
      without processes for at least 10 days in the presence of RPE-CM and expressed
      opsin during this period. Conditioned medium from the flat-cell monolayers did
      not support photoreceptor differentiation or their survival. However, the
      presence of flat cells was a requisite to achieve any neurite outgrowth even in
      the presence of RPE-CM. In the absence of RPE-CM, neither photoreceptors nor flat
      cells survived or proliferated. Heat and trypsin treatment of the RPE-CM
      abolished all its growth-supporting activities which indicates its proteinaceous
      nature. This represents the first time in vitro that an RPE-derived factor(s) has
      been shown to be responsible for photoreceptor cell survival and differentiation.

PMID- 1385583
TI  - The effect of the neurotoxin DSP4 on the development of a predisposition in the
      domestic chick.
AB  - Under certain conditions, dark-reared chicks preferentially approach objects
      resembling conspecifics. In the current study we investigated the effect of the
      catecholaminergic neurotoxin DSP4 on this predisposition. After hatching, chicks
      received an intraperitoneal injection of either DSP4 or vehicle (controls). The
      chicks were individually placed in running wheels for 2 x 1 hr, 24 hr before
      testing. The chicks were maintained in darkness until given a preference test,
      which involved the simultaneous presentation of an illuminated red box and a
      stuffed fowl at 36, 48, 60, 66, or 72 hr after hatching. The approach of each
      chick toward the two objects was recorded over 5 min and a preference score
      calculated. Control chicks placed in the running wheels at 24 and 36 hr posthatch
      and tested 24 hr later showed a significant preference for the fowl compared to
      the red box. In contrast, DSP4-treated chicks did not show such a preference at
      corresponding ages, but did express a greater preference for the fowl when placed
      in the running wheels at 42 and 48 hr posthatch and tested 24 hr later. These
      results suggest that experience of the running wheel or of associated factors,
      e.g., handling, must occur during a restricted period of time to influence the
      emergence of the predisposition to approach the stuffed fowl. DSP4 treatment
      delays the onset of this period.

PMID- 1385584
TI  - The basis of decreased recombination in certain outcrosses of Neurospora crassa.
AB  - Crossing over in a multiply marked segment of linkage group I was conspicuously
      reduced in outcrosses between a marked laboratory strain and each of six
      unrelated wild-collected strains, compared with crosses between inbred laboratory
      strains. The marked chromosome segment was transferred intact from the inbred
      strain to one of the wild-collected strains by seven recurrent backcrosses, and
      conversely, the corresponding segment of the wild strain was transferred to the
      inbred background by backcrossing to the multiply marked laboratory strain.
      Recombination was then monitored in crosses from parents having the marked and
      unmarked chromosome segments from the same or from unrelated sources. Meiotic
      crossing-over in the marked segment remained low in crosses between parents that
      were dissimilar with respect to genetic background, but crossing over was
      restored to a high level when the genetic background of both parents was that of
      the inbred laboratory strain, regardless of the source of the marked segments.
      Reduced recombination in outcrosses was therefore not due to heterologies in the
      marked segment but must be attributed to modifiers that are unlinked or distant
      from the monitored region.

PMID- 1385585
TI  - Age stability of human brain 5-HT terminals studied with [3H]paroxetine binding.
AB  - The effect of age on serotonin uptake sites labeled with [3H]paroxetine was
      studied in two sets of brains. The first set included 28 subjects (19 males and 9
      females) between the ages 0 and 100 years. The cortex of cingulate gyrus and the
      amygdala were studied. No age-related changes in binding capacity (Bmax) or
      binding affinity (Kd) were noted. In the second set, the frontal cortex and
      hypothalamus from 22 subjects (18 males and 4 females) between 16 and 75 years
      were studied. No age-related changes in the binding were observed. The interval
      between death and freezing of the tissue did not influence the binding. Regarding
      the [3H]paroxetine binding as an indirect marker for 5-HT terminals, the data
      suggest a stability of 5-HT terminals with increasing age in the human brain.

PMID- 1385587
TI  - No place to go: refusal of life-sustaining treatment by competent persons with
      physical disabilities.

PMID- 1385588
TI  - Suicide intervention for people with disabilities: a lesson in inequality.

PMID- 1385586
TI  - Effect of oral clodronate on bone pain. A controlled study in patients with
      metastic prostatic cancer.
AB  - Although osteosclerotic metastases are characteristic of prostatic carcinoma,
      bone resorption is also accelerated. Since clodronate inhibits bone resorption
      and relieves bone pain, we have given it to patients with painful bone disease
      from prostatic cancer after failure of hormonal therapy. All patients received
      estramustine phosphate orally. Simultaneously they were randomly allocated to
      clodronate (36) and placebo (39) groups. Clodronate was given by mouth. The dose
      was 3.2 g for the first month, thereafter 1.6 g. Pain relief was more distinct in
      the clodronate group where one third of patients were totally free of bone pain.
      The use of analgesics stopped in 38% of patients on clodronate and in 18% on
      placebo which effect probably belongs to estramustine phosphate. Serum calcium
      concentration decreased more markedly in the clodronate group. Clodronate dose of
      3.2 g seemed to be more potent than that of 1.6 g. Side effects were uncommon and
      occurred equally in both groups. No significant differences were seen in median
      survival or survival rates between the groups.

PMID- 1385589
TI  - Withdrawing life-sustaining treatment from people with severe disabilities who
      request it: equal protection considerations.

PMID- 1385590
TI  - Protective efficacy of clarithromycin and its 14-hydroxy metabolite against
      Haemophilus influenzae in a murine septicaemia model.

PMID- 1385591
TI  - Psychosocial adaptation of fathers of children with autism, Down syndrome, and
      normal development.
AB  - Fathers have been largely neglected in previous research of families of autistic
      children. We compared fathers of 20 autistic, 20 Down syndrome, and 20
      developmentally normal children on several measures of psychosocial adaptation.
      Groups were matched on child's adaptive behavior age equivalent, gender, birth
      order, family size, and SES. The three groups differed significantly on measures
      of intrapersonal and family functioning but not on social-ecological variables.
      Fathers of children with autism or Down syndrome reported more frequent use of
      wish-fulfilling fantasy and information seeking as coping strategies as well as
      more financial impact and disruption of family activities than did fathers of
      developmentally normal children. There were few significant differences between
      fathers of children with autism and those of children with Down syndrome. These
      results suggest that fathers adapt relatively well to the demands associated with
      raising a child with a developmental disability.

PMID- 1385592
TI  - In vivo and in vitro characterization of the secA gene product of Bacillus
      subtilis.
AB  - The putative amino acid sequence from the wild-type Bacillus subtilis div+ gene,
      which complements the temperature-sensitive div-341 mutation, shares a 50%
      identity with the sequence from Escherichia coli secA (Y. Sadaie, H. Takamatsu,
      K. Nakamura, and K. Yamane, Gene 98:101-105, 1991). The B. subtilis div-341
      mutant accumulated the precursor proteins of alpha-amylase and beta-lactamase at
      45 degrees C as in the case of sec mutants of E. coli. The div-341 mutation is a
      transition mutation causing an amino acid replacement from Pro to Leu at residue
      431 of the putative amino acid sequence. The B. subtilis div+ gene was
      overexpressed in E. coli under the control of the tac promoter, and its product
      was purified to homogeneity. The Div protein consists of a homodimer of 94-kDa
      subunits which possesses ATPase activity, and the first 7 amino acids of the
      putative Div protein were found to be subjected to limited proteolysis in the
      purified protein. The antiserum against B. subtilis Div weakly cross-reacted with
      E. coli SecA. On the other hand, B. subtilis Div could not replace E. coli SecA
      in an E. coli in vitro protein translocation system. The temperature-sensitive
      growth of the E. coli secA mutant could not be restored by the introduction of B.
      subtilis div+, which is expressed under the control of the spac-1 promoter, and
      vice versa. The B. subtilis div+ gene is the B. subtilis counterpart of E. coli
      secA, and we propose that the div+ gene be referred to as B. subtilis secA,
      although Div did not function in the protein translocation system of E. coli.

PMID- 1385593
TI  - Mutational analysis of the glycine-rich region of the c subunit of the
      Escherichia coli F0F1 ATPase.
AB  - Eight strains carrying amino acid substitutions within the c subunit of the F0F1
      ATPase of Escherichia coli have been constructed by using site-directed
      mutagenesis. Three strains carrying the substitutions Gly-23----Leu, Ala-24---
      Leu, and Gly-38----Leu, which reside in or near the highly conserved glycine-rich
      region of the c subunit, are unable to carry out oxidative phosphorylation.
      Membranes prepared from these strains possess basal levels of ATPase activity. In
      contrast, strains carrying the substitutions Ile-30----Phe, Gly-33----Leu, Gly-58
      ---Leu, and Lys-34----Val and the Lys-34----Val, Glu-37----Gln double
      substitution were found to possess a coupled phenotype similar to that of the
      wild type.

PMID- 1385594
TI  - Biosynthesis of D-alanyl-lipoteichoic acid: cloning, nucleotide sequence, and
      expression of the Lactobacillus casei gene for the D-alanine-activating enzyme.
AB  - The D-alanine-activating enzyme (Dae; EC 6.3.2.4) encoded by the dae gene from
      Lactobacillus casei ATCC 7469 is a cytosolic protein essential for the formation
      of the D-alanyl esters of membrane-bound lipoteichoic acid. The gene has been
      cloned, sequenced, and expressed in Escherichia coli, an organism which does not
      possess Dae activity. The open reading frame is 1,518 nucleotides and codes for a
      protein of 55.867 kDa, a value in agreement with the 56 kDa obtained by
      electrophoresis. A putative promoter and ribosome-binding site immediately
      precede the dae gene. A second open reading frame contiguous with the dae gene
      has also been partially sequenced. The organization of these genetic elements
      suggests that more than one enzyme necessary for the biosynthesis of D-alanyl
      lipoteichoic acid may be present in this operon. Analysis of the amino acid
      sequence deduced from the dae gene identified three regions with significant
      homology to proteins in the following groups of ATP-utilizing enzymes: (i) the
      acid-thiol ligases, (ii) the activating enzymes for the biosynthesis of
      enterobactin, and (iii) the synthetases for tyrocidine, gramicidin S, and
      penicillin. From these comparisons, a common motif (GXXGXPK) has been identified
      that is conserved in the 19 protein domains analyzed. This motif may represent
      the phosphate-binding loop of an ATP-binding site for this class of enzymes. A
      DNA fragment (1,568 nucleotides) containing the dae gene and its putative
      ribosome-binding site has been subcloned and expressed in E. coli. Approximately
      0.5% of the total cell protein is active Dae, whereas 21% is in the form of
      inclusion bodies. The isolation of this minimal fragment without a native
      promoter sequence provides the basis for designing a genetic system for
      modulating the D-alanine ester content of lipoteichoic acid.

PMID- 1385595
TI  - Regulation of katF and katE in Escherichia coli K-12 by weak acids.
AB  - Chromosomal transcriptional and translational lacZ fusions to the katE
      (structural gene for the HPII hydroperoxidase) and katF (putative sigma factor
      required for katE expression) genes of Escherichia coli were isolated, and the
      regulation of these fusions was used to identify factors that control the
      expression of these two important antioxidant factors. While katE was found to be
      regulated primarily at the level of transcription (since induction patterns were
      similar for both transcriptional and translational fusions), katF expression was
      a function of both transcriptional and translational signals. The katE gene was
      induced 57-fold as cells entered the stationary phase, while katF was induced 23
      fold. katF induction was coincident with katE induction and occurred at the onset
      of the stationary growth phase. Expression of both katE and katF could be induced
      by resuspending uninduced exponential-phase cells in spent culture supernatant
      recovered from stationary-phase cells. The component of stationary-phase culture
      supernatant responsible for induction of the katF regulon appeared to be acetate,
      since expression of both katE and katF fusions was induced when exponential-phase
      cells were exposed to this weak acid. Other weak acids, including propionate and
      benzoate, were also found to be effective inducers of expression of both katF and
      katE. Induction of katE and katF fusions was unaffected in merodiploid strains
      containing both mutant and wild-type alleles, indicating that expression of both
      genes is independent of the wild-type gene product. Examination of catalase
      zymograms prepared from cells exposed to various levels of acetate revealed that
      both HPI and HPII catalases are induced by this weak acid, suggesting that there
      is a common link in the regulation of these two enzymes.

PMID- 1385597
TI  - Inhibition of heterotopic osteogenesis in rats by a new bioerodible system for
      local delivery of indomethacin.
AB  - A study was done to evaluate the effect of a system for the local delivery of
      indomethacin on demineralized bone-induced formation of heterotopic bone in the
      abdominal muscles of rats. Two separate investigations were conducted on a total
      of forty-eight Wistar rats. In both series, two types of implants were used:
      polyorthoester and demineralized bone (Group A, the control group) and
      polyorthoester with 5 per cent indomethacin and demineralized bone (Group B, the
      experimental group). In the first series, host-tissue responses and
      osteoinduction were evaluated histologically at two, three, and four weeks after
      the implantation. In the second series, the formation of bone was quantified on
      the basis of uptake of 85Sr at four weeks after the implantation. The
      polyorthoester system for the local delivery of indomethacin significantly
      inhibited demineralized bone-induced heterotopic formation of bone, as
      demonstrated by light microscopy and by uptake of 85Sr. The polyorthoester, with
      or without the drug, caused little tissue reaction and was resorbed almost
      completely at four weeks.

PMID- 1385596
TI  - Role of the MetR regulatory system in vitamin B12-mediated repression of the
      Salmonella typhimurium metE gene.
AB  - The vitamin B12 (B12)-mediated repression of the metE gene in Escherichia coli
      and Salmonella typhimurium requires the B12-dependent transmethylase, the metH
      gene product. It has been proposed that the MetH-B12 holoenzyme complex is
      involved directly in the repression mechanism. Using Escherichia coli strains
      lysogenized with a lambda phage carrying a metE-lacZ gene fusion, we examined B12
      mediated repression of the metE-lacZ gene fusion. Although B12 supplementation
      results in a 10-fold repression of metE-lacZ expression, homocysteine addition to
      the growth medium overrides the B12-mediated repression. In addition, B12
      mediated repression of the metE-lacZ fusion is dependent on a functional MetR
      protein. When a metB mutant was transformed with a high-copy-number plasmid
      carrying the metE gene, which would be expected to reduce intracellular levels of
      homocysteine, metE-lacZ expression was reduced and B12 supplementation had no
      further effect. In a metJ mutant, B12 represses metE-lacZ expression less than
      twofold. When the metJ mutant was transformed with a high-copy-number plasmid
      carrying the metH gene, which would be expected to reduce intracellular levels of
      homocysteine, B12 repression of the metE-lacZ fusion was partially restored. The
      results indicate that B12-mediated repression of the metE gene is primarily a
      loss of MetR-mediated activation due to depletion of the coactivator
      homocysteine, rather than a direct repression by the MetH-B12 holoenzyme.

PMID- 1385598
TI  - Exclusion of close linkage of bipolar disorder to dopamine D1 and D2 receptor
      gene markers.
AB  - A potential role of dopamine in bipolar disorder has been suggested by several
      strands of evidence, namely the ability of dopaminergic agonists to induce mania
      and the effects of lithium, carbamazepine and the antipsychotics on central
      dopamine receptors and/or turnover. We therefore aimed to determine if bipolar
      disorder in two large bipolar pedigrees was linked to the recently cloned
      dopamine D1 (DRD1) and D2 (DRD2) receptors. (These have been mapped to
      chromosomal regions 5q35.1 and 11q22.3-q23, respectively). Linkage of bipolar
      disorder and recurrent depression to DRD1 and DRD2 was tested using a series of
      genetic models with varying penetrance levels. Additionally, linkage was examined
      using a series of levels of definitions of affective status (ranging from bipolar
      I alone to all affective illnesses). Close linkage to these markers was strongly
      excluded using each model and definition. The findings for DRD1 also persisted
      when a wide range of rates of 'sporadic' (non-genetic) presentations of illness
      were incorporated in the analysis, but the DRD2 results did not remain
      statistically significant at high sporadic rates. The exclusion of linkage to
      DRD2 is consistent with other recent reports.

PMID- 1385599
TI  - Facet theoretic analysis of the Hamilton-D scale.
AB  - The items of the HAM-D(17-item version) were analyzed by a nonmetric (ordinal)
      multi-dimensional scaling procedure (Smallest Space Analysis, SSA-I) and the
      structure of the test items characterized within the framework of Guttman's facet
      theory. Two systematic components (facets) were discerned: 'centrality' and
      'aspect'. Properties of the facets as well as their relations were assessed and
      examined empirically by analyzing the inter-relations among different items. The
      spatial configurations obtained by the scaling procedure were found only
      partially to fit the expectations derived from the facet-theory model. The facet
      'centrality' was found to have a strong overriding influence over the 'aspect'
      facet. The results suggest the value of a new combination and selection of items
      reflecting different facets of depression consistently over time.

PMID- 1385600
TI  - Feeding patterns, food energy, nutrient intakes, and anthropometric measurements
      of selected black preschool children with Down syndrome.

PMID- 1385601
TI  - [Laparoscopic hysterectomy. Results in 44 cases].
AB  - Laparoscopic hysterectomy is a recent procedure. We present our preliminary
      results about 44 patients. In 77.3% of cases (34 patients) the operation was
      carried out completely by laparoscopy and 10 patients (22.7%) required conversion
      of the laparoscopy to a standard laparotomy. The indications for laparotomy were:
      hemostasis difficulties (6 cases); bladder injury (1 case); inability to expose
      the uterine pedicles and or the ureter (3 cases). Three post-operative
      complications occurred: one small bowel occlusion which was explored by
      laparoscopy, and two infection treated by antibiotics only. These preliminary
      results enable us: to affirm that laparoscopic hysterectomy is feasibility
      without an important risk of per and or post-operative complications. to specify
      the four situations in which laparoscopic surgery is particularly advantageous
      for hysterectomy: absence of genital prolapse; when uni or bilateral adnexectomy
      is required; previous past-history of abdomino-pelvic surgery, salpingitis,
      endometriosis ...; neoplastic pathologies (lymphadenectomy); to propose a
      laparoscopic hysterectomy classification.

PMID- 1385602
TI  - [Laparoscopy, appendicitis and pregnancy].

PMID- 1385603
TI  - Ondansetron, a 5-HT3 receptor antagonist, partially attenuates the effects of
      amphetamine: a pilot study in healthy volunteers.
AB  - Preclinical studies suggest that 5-HT3 antagonists modulate dopamine-mediated
      responses in the limbic system and may therefore have a therapeutic role in
      psychiatry. We have examined the effect of ondansetron, a specific 5-HT3
      antagonist, on the psychological and psychomotor changes induced by amphetamine
      in human volunteers. Nine healthy males took part in this double-blind placebo
      controlled balanced-crossover study. Each subject received one of three
      treatments in a randomised manner: (a) placebo/placebo; (b) placebo/amphetamine
      (15 mg); (c) ondansetron (4 mg)/amphetamine (15 mg). Subjects were assessed for
      self-ratings of hunger, mood, energy, alertness, restlessness, irritability, and
      asked to rate the abnormality of their overall subjective state. In addition,
      systolic blood pressure, and performance on psychomotor tests were repeatedly
      assessed. Although amphetamine did not cause any significant changes in self
      rating of mood, energy, alterness, restlessness or irritability, it induced a
      significant increase in self-ratings for overall subjective state, and a
      significant decrease in self-ratings of hunger. Amphetamine also caused an
      increase in systolic blood pressure and a decrease in the mean time taken to
      complete the psychomotor tests. Pretreatment with ondansetron attenuated the
      effects of amphetamine on hunger and subjective state, but not on blood pressure
      or psychomotor performance tests. These findings suggest that in humans 5-HT3
      receptor antagonists may partially modify the subjective effects of amphetamine,
      and are in keeping with results from animal studies that 5-HT3 receptor
      antagonists might affect neurotransmission within mesolimbic brain regions.
      However, it was not possible to exclude a pharmacokinetic interaction to explain
      the effects of ondansetron.

PMID- 1385604
TI  - Evidence for extrathymic development of TNK cells. NK1+ CD3+ cells responsible
      for acute marrow graft rejection are present in thymus-deficient mice.
AB  - The predominant mechanism responsible for acute specific rejection of allogeneic
      and parental bone marrow by irradiated mice is due to a cell (TNK) that expresses
      the NK cell surface markers NK1 and ASGM1 as well as TCR. Here we analyze the
      question as to whether TNK cells require a functional thymus for their
      development. Using adoptive cell transfer assays, evidence is presented that, as
      is the case in normal mice, NK1+ CD3+ effector cells are responsible for
      rejection in thymus-deficient nude mice and that the specificity of rejection is
      indistinguishable from that of normal mice. To reveal the presence of TNK cells
      in the spleen of nude mice, double staining for NK1 and CD3 followed by FACS
      analysis was done. It is shown that NK1+ CD3+ cells are present in the spleens of
      nude but not euthymic mice, suggesting that the lack of a functional thymus
      stimulates either Ag expression or the number of TNK cells. In support of this
      finding, the treatment of irradiated marrow reconstituted mice with cyclosporin A
      leads to the appearance of TNK cells in the spleen. The relative efficiency of
      spleen cells from nude and cyclosporin A-treated mice to transfer resistance in
      adoptive cell transfers was assessed and found to be higher than that of normal
      spleen, consistent with the higher frequency of these cells in thymus-defective
      mice. The fate of NK1+ CD3+ cells subsequent to stimulation with an allogeneic
      marrow graft indicates that these cells proliferate in nude mice without gaining
      cytolytic activity. In euthymic mice, however, NK1+ CD3+ cells appear transiently
      but disappear in favor of CD4+ and CD8+ cells that proliferate in response to an
      allogeneic marrow graft. The CD8+ cells express cytolytic activity with
      specificity similar to that of the acute rejection mechanism, consistent with the
      suggestion that TNK cells differentiate into CD8+ killer cells. The reason why
      TNK cells in nude mice fail to differentiate into CD8+ CTL is explained by the
      lack of Th cells.

PMID- 1385605
TI  - Developmentally regulated expression of the beta 4 integrin on immature mouse
      thymocytes.
AB  - Integrins are a superfamily of alpha beta heterodimers, most of which serve as
      cell surface receptors for extracellular matrix proteins. In this report, we
      demonstrate that the recently described alpha 6 beta 4 integrin, previously
      thought to be limited to epithelial cells and Schwann cells, is expressed on
      immature mouse thymocytes. The presence of alpha 6 beta 4 is controlled by
      regulation of beta 4 expression, because alpha 6 was expressed by virtually all
      cells examined, paired with the beta 1 integrin chain to form VLA-6. During fetal
      ontogeny, beta 4 was highly expressed by 35% of day-13 thymocytes, 75% of day-14
      to -15 thymocytes, then rapidly declined to low levels by birth. In neonates and
      adults, beta 4 expression was highest on CD4- CD8- CD3- and TCR(+)-gamma delta
      subsets. Correlation of IL-2R, CD44 and beta 4 on CD4- CD8- thymocytes revealed
      maximal levels on the intermediate CD44- IL-2R+ subset. Most CD4- CD8+ TCR-
      thymocytes and a significant fraction of CD4+ CD8+ thymocytes were beta 4lo,
      whereas the most mature J11d- single positive thymocytes were beta-4. Overall,
      down-regulation of beta 4 was associated with up-regulation of CD4, CD8, and CD3
      in the thymus. alpha 6 beta 4 was undetectable on fetal liver or bone marrow
      cells, lymphocytes from lymph node, spleen, or blood, and mitogen-activated
      splenic T cells cultured up to 10 wk with IL-2. The data suggest that alpha 6
      beta 4 is up-regulated after pro-T cells enter the thymus and may have a thymus
      specific function for T cells. The developmentally regulated pattern of
      expression and the prominence of alpha 6 beta 4 on day-13 to -16 fetal and adult
      CD4- CD8- CD3- thymocytes further suggest this unusual integrin may play a role
      in early T cell development, including stages before acquisition of the TCR.

PMID- 1385606
TI  - The N-terminus and C-terminus of IFN-gamma are binding domains for cloned soluble
      IFN-gamma receptor.
AB  - The mechanism of binding of murine IFN-gamma to its receptor has not been
      determined. We have studied this mechanism by examining the binding of
      overlapping synthetic peptides of IFN-gamma to cloned soluble murine IFN-gamma R.
      IFN-gamma (1-39) and IFN-gamma (95-133) were able to compete with [125I]IFN-gamma
      for binding to cloned soluble receptor. Peptides corresponding to the inner
      region of IFN-gamma--IFN-gamma (36-60), IFN-gamma (54-91), and IFN-gamma (78-107)
      -showed a markedly reduced ability to compete with [125I]IFN-gamma for receptor
      binding relative to the N-terminal and C-terminal peptides. In direct binding
      studies, the binding of [125I]-IFN-gamma (1-39) to soluble receptor could only be
      competed by IFN-gamma (1-39) and IFN-gamma and not by any of the other peptides
      including IFN-gamma (95-133). This suggests that the N- and C-termini of IFN
      gamma bind to different regions of the receptor. These data in conjunction with
      previous structure/function studies and x-ray crystallographic data have allowed
      us to formulate a "velcro-key" model of IFN-gamma binding to receptor that
      involves both the N- and C-terminal domains. The N-terminus binds in the
      classical "lock-and-key" manner characterized by specific ligand-receptor
      binding. The hydrophilic C-terminus binds to a region of the receptor distinct
      from the N-terminus likely through the polycationic region, which is conserved
      across species barriers. Binding of this type would exhibit high affinity and low
      specificity similar to a piece of velcro. This interaction becomes specific when
      the C-terminus is in the context of the whole IFN-gamma molecule and may act to
      increase the affinity of receptor binding and/or facilitate signal transduction.

PMID- 1385607
TI  - Lymphocyte development of adherence and motility in extracellular matrix during
      IL-2 stimulation.
AB  - To extravasate into normal and neoplastic tissue, lymphocytes must migrate
      through the subendothelial basement membrane and underlying interstitium,
      structures rich in extracellular matrix (ECM). We have performed a time-course
      study of the development of motility in ECM by murine lymphocytes during in vitro
      exposure to high titers of IL-2 (1000 Cetus units/ml). This protocol generates
      immunotherapeutic lymphocyte populations expressing lymphokine-activated killer
      activity. Spontaneous motility was measured in three-dimensional gels of type I
      (interstitial) collagen or Matrigel, a model basement membrane. A newly developed
      assay permitted not only the measurement of distance traveled by the leading cell
      front, but also the separation of lymphocytes on the basis of three types of
      behavior. The motile fraction consisted of lymphocytes that penetrated beneath
      the ECM gel surface during an 18-h migration period. There were also two
      nonmotile fractions: the nonadherent fraction, which failed to bind to the gel
      surface; and the adherent fraction, which bound but did not penetrate during the
      assay period. During a 3- to 5-day exposure to high titer IL-2, both adherence
      and motility increased significantly. In type I collagen, cells of the NK lineage
      developed greater surface adherence and less motility than cells of the T
      lineage. The surface-adherent fraction expressed higher lymphokine-activated
      killer and NK activity than did the nonadherent or motile fractions. Under
      prolonged IL-2 stimulation (7 to 12 days), there was a decline in the percentage
      of cells exhibiting motility in both types of ECM, and an increase in the
      percentage of surface-adherent cells. The findings indicate that the behavior of
      an IL-2-stimulated lymphocyte population in ECM is profoundly influenced by the
      duration of IL-2 exposure. Furthermore, lack of lymphocyte motility may reflect
      two different behaviors, nonadherence and adherence without motility. The
      nonadherent and surface-adherent populations may differ in phenotypic
      distribution and function. The motility system described in this report will be
      useful in separating and studying the mechanisms that produce lymphocyte
      adherence and motility, and in understanding the in vivo implications of these
      behaviors.

PMID- 1385608
TI  - Effects of similarity and repetition on memory: registration without learning?
AB  - We investigated judgments of the frequency of test items (Y) that were highly
      similar to studied items (X) to test a prediction made by several memory models:
      that the judged frequency of Y should be proportional to the judged frequency of
      X. Whether stimuli were pictures or words, judged frequency of Y was bimodally
      distributed with 1 mode at zero, suggesting that frequency judgments involve a 2
      stage process in which a zero judgment is made if there is a mismatch between
      retrieved information and the test item. Nonzero judgements, taken by themselves,
      were consistent with the prediction of proportionality. In 2 experiments, the
      percentage of zero judgments made to Y increased with repetition of X, but in 2
      others the percentage did not change beyond frequency = 1. The percentage of
      "new" judgments in recognition memory followed this same pattern. Because the
      judged frequency of X increased even as X-Y discrimination showed no improvement,
      we characterize the result as "registration without learning."

PMID- 1385609
TI  - Subjective memorability and the mirror effect.
AB  - The mirror effect refers to the common finding that hit and false alarm rates on
      a recognition test are inversely related. The present research investigated the
      generality of the mirror effect (to rare words) and tested whether the effect
      might be grounded in accurate estimates of word memorability. The first 2
      experiments showed that although high- and low-frequency words exhibit a mirror
      effect, rare words do not. Furthermore, contrary to expectations, Ss consistently
      (and mistakenly) predicted that memorability was directly correlated with
      frequency of usage. These findings weight against the idea that the mirror effect
      arises because of a S's ability to reject low-frequency lures on the grounds that
      such words would have been remembered had they appeared previously. Instead, the
      rejection of lures from different frequency categories may be determined by their
      semantic or phonemic overlap with list targets, and an analysis along these lines
      may help to explain why rare words constitute an exception to the otherwise
      ubiquitous mirror effect.

PMID- 1385610
TI  - On the relationship between recall and recognition memory.
AB  - The relationship between recall and recognition has been a central topic for the
      study of memory. A test of alternative views about recall and recognition was
      arranged by studying amnesic patients. In amnesia, damage has occurred to a brain
      system important for declarative (conscious) memory, but skill learning, priming,
      and other forms of nonconscious memory are intact. Recall and recognition were
      found to be proportionately impaired in amnesic patients, and confidence ratings
      for the recognition judgments were commensurate with the level of impaired
      performance. The results are contrary to views that either recognition memory or
      associated confidence judgments are ordinarily supported significantly by
      nonconscious memory. The results favor the view that recall and recognition are
      related functions of declarative memory and equivalently dependent on the brain
      system damaged in amnesia.

PMID- 1385612
TI  - Children's and adults' reading of nonwords: effects of regularity and
      consistency.
AB  - The procedures used by novice readers to assemble pronunciations for nonwords
      were investigated. Children in Grades 1-3 read aloud consonant-vowel-consonant
      and longer monosyllabic nonwords. By the end of Grade 1, children displayed a
      good grasp of grapheme-phoneme (G-P) correspondences (e.g., ai, ow). Grade 2 and
      3 readers increasingly used larger orthographic correspondences termed rimes
      (e.g., -ook, -ild). However, G-P correspondences determined most responses.
      Adults likewise used G-P rules when reading aloud nonwords and were more accurate
      at applying the rules. The strong reliance of Grade 1 and 2 readers on G-P rules
      was also demonstrated by their superior oral reading of regular words along with
      a tendency to regularize exception words (e.g., reading bull to rhyme with dull).

PMID- 1385611
TI  - Influence of contextual features on the activation of ambiguous word meanings.
AB  - Three studies examined whether initial meaning activation is sensitive to
      context. Experiment 1 demonstrated that contextually appropriate targets were
      activated more than inappropriate targets. Experiment 2 evaluated activation
      across intervals of 0, 300, and 600 ms. Constraining sentences activated
      contextually appropriate meanings over inappropriate meanings. This was
      maintained across the intervals for highly salient targets. Less-salient targets,
      although initially activated, were no longer activated 300 ms following the
      homograph. Experiment 3 converged on context-sensitive activation following a 50
      ms exposure of the sentence-final homograph. Conclusions are (a) initial meaning
      activation can be sensitive to context, (b) when a homograph is instantiated, it
      is congruent with a broad scope of targets, and (c) less-salient targets receive
      less activation over the time course.

PMID- 1385613
TI  - Nonword naming: further exploration of the pseudohomophone effect in terms of
      orthographic neighborhood size, graphemic changes, spelling-sound consistency,
      and reader accuracy.
AB  - Five experiments examined nonword pronunciation. As reported by McCann and Besner
      (1987), accurate, regular pronunciations increased as the number of orthographic
      neighbors (N) increased. Adults read pseudohomophones (nonwords that sound like a
      word) more accurately than other nonwords only when the nonwords were low n,
      shared the consonants with the words on which they were based, and overall
      accuracy was lower. Children showed a pseudohomophone advantage even when N was
      high. Adults pronounced nonwords comprised of inconsistent endings (with existing
      regular and irregular pronunciations) in an irregular fashion when this resulted
      in a word; this applied to relatively high-N items.

PMID- 1385614
TI  - Reaction time measures of spelling: testing a two-strategy model of skilled
      spelling.
AB  - Two strategies have been suggested to be important in skilled English spelling: a
      lexical strategy, which relies on word-specific graphemic information, and a rule
      strategy, which relies on phoneme-to-grapheme correspondences. Limitations in the
      usefulness of spelling accuracy as a dependent variable make it difficult to test
      claims about how the strategies might work together. Two experimental paradigms
      that measure both spelling accuracy and time are suggested to be useful. Results
      produced with the paradigms were consistent with the claims that skilled spellers
      make use of both strategies and that the lexical strategy is more useful than the
      rule strategy. Working memory may be important in combining products of both
      strategies. Results were inconsistent with the claim that the rule strategy is
      invoked only when the lexical strategy fails to produce a complete spelling.

PMID- 1385615
TI  - Comprehension strategies in the development of a mental model.
AB  - It is generally assumed that the comprehension strategy used in the development
      of a mental model for narrative texts focuses on information that is relevant to
      the protagonist. Experiments 1a and 1b confirmed that readers remain sensitive to
      the location of the protagonist even when strategies based on text-base level
      representations predict this information should not be active. Experiments 2 and
      3 tested the stronger claim that readers adopt the perspective of the
      protagonist. Ss did not notice information that was contradictory from the
      perspective of the protagonist unless explicitly instructed to adopt that
      perspective. It was concluded that, at the level of the mental model, readers
      focus on information relevant to the protagonist but that they do not adopt the
      perspective of the protagonist unless characteristics of the text induce such a
      strategy.

PMID- 1385616
TI  - Conscious knowledge and changes in performance in sequence learning: evidence
      against dissociation.
AB  - Two experiments examined the relation between explicit knowledge and motor
      performance on the serial reaction time task developed by Nissen and Bullemer
      (1987). Tests of free recall and recognition of sequence components revealed that
      reliable explicit knowledge was acquired after an amount of practice that was
      hardly sufficient to improve mean motor performance. In addition, reaction time
      improvement was limited to the ending trials of the 3- and 4-trial sequence
      components that Ss recalled or recognized. These results were replicated in
      Experiment 3, in which Ss were trained under attentional distraction in the task
      developed by Cohen, Ivry, and Keele (1990). Overall, these findings undermine the
      most direct experimental support for the widespread view that conscious knowledge
      and performance in sequence-learning tasks tap 2 independent knowledge bases in
      normal Ss.

PMID- 1385617
TI  - Persistence of stimulus-response compatibility effects with extended practice.
AB  - The influence of extended practice on stimulus-response (S-R) compatibility
      effects was investigated. Three experiments, each extending over a period of 8
      sessions, were conducted. The nature and degree of compatibility was manipulated
      across experiments. In all experiments, a persistent effect of S-R compatibility
      on reaction times was observed. Thus, the lower bound for reaction times appears
      to be less for compatible assignments than for incompatible assignments. This
      persistence of S-R compatibility indicates that the initial codings used to
      perform a novel task continue to exert an influence on later performance.

PMID- 1385619
TI  - Reasoning with conditionals containing negated constituents.
AB  - Three experiments investigated matching bias in conditional reasoning tasks.
      Matching bias occurs when Ss ignore negations and match named items. Experiment 1
      used an abstract and a thematic version of Evans's (1972) construction task.
      Results showed that matching may be due to an interaction between task demands
      and constructing contrast classes when interpreting negations. Experiment 2,
      which used Wason's (1968) selection task, introduced a manipulation to ease
      contrast-class construction. Confirmation plus falsification dominated over
      matching. Experiment 3 introduced two other manipulations to aid contrast-class
      construction with abstract material. Confirmation was facilitated, matching was
      suppressed, and falsification remained unchanged. These results suggest that
      matching occurs only when insufficient or ambiguous information prevents the
      intended interpretation of negations.

PMID- 1385618
TI  - Differential effects of voluntary expectancies on reaction times and event
      related potentials: evidence for automatic and controlled expectancies.
AB  - Expectancy has been used to explain the effects of stimulus sequences both on
      reaction times (RTs) and on the P300 component of the human event-related
      potential. However, there are conflicting views about the control obtainable over
      these underlying expectancies. We compared the effects of voluntary expectancies
      for stimulus changes or repetitions in random tone series on RTs and the P300. Ss
      responded according to either stimulus identity (Experiment 1) or stimulus
      sequence (Experiment 2). In both experiments RTs were strongly affected by event
      expectedness. P300 amplitude, on the other hand, was affected (as a trend) only
      in Experiment 2. The results suggest that there are at least 2 types of
      "expectancy", one that is largely automatic and inflexible, reflected in P300
      amplitude, and a second, controlled process that is reflected mainly in RT. The
      latter type of expectancy appears to affect processing stages beyond stimulus
      evaluation and classification.

PMID- 1385620
TI  - Effects of probability mode on preference reversal.
AB  - Six analysts estimated verbally and numerically the chances that specific events
      will occur. Sixty decision makers used each type of estimate to make binary
      choice decisions and to bid for lotteries based on the events. The usual reversal
      of preference between choice and bidding procedures was found in the numerical
      condition, but the frequency of preference reversals was significantly reduced in
      the verbal condition. This reduction occurred because risk aversion was reduced
      in choice when verbal estimates were given, whereas bidding was unaffected by
      presentation mode. The pattern of results was predicted by and supports the
      hypothesis that the relative importance given to the dimensions of a prospect
      depends on the form in which the information is displayed.

PMID- 1385621
TI  - Alphabetic sequence decisions for letter pairs with separations of one to three
      letters.
AB  - The alphabet storage and retrieval theory of Klahr, Chase, and Lovelace (1983)
      was tested for applicability to letter-order decisions. Ss judged whether letter
      pairs with sequential separations of 1, 2, or 3 letters were in correct or
      incorrect order. Ss made decisions either in a continuous- or intermittent
      attention mode. The results for alphabetic letter-order decisions with a letter
      separation of 1 were in conformance with the theory of Klahr et al. in both
      attention modes. However, at letter separations of 2 and 3 letters, Ss made
      decisions that were more compatible with a symbolic-distance mechanism.
      Speculation on how Ss could make alphabetic-order decisions in either a memory
      consultation or a symbolic-distance manner is made.

PMID- 1385622
TI  - Adaptive behavior after depressive illness in Down's syndrome.

PMID- 1385623
TI  - Immunocytochemical detection of the growth-associated protein B-50 by newly
      characterized monoclonal antibodies in human brain and muscle.
AB  - The growth-associated protein B-50 also termed GAP-43, F1, pp46, P-57 and
      neuromodulin is a nervous tissue-specific protein kinase C (PKC) substrate that
      is considered to play a major role in neurite formation, regeneration, and
      neuroplasticity. We describe the isolation of seven mouse monoclonal antibodies
      (Mabs) directed against B-50. The Mabs are produced against the bovine B-50,
      selected by ELISA for cross-reactivity with its human counterpart, and evaluated
      on Western blots in comparison with the well-characterized affinity-purified
      rabbit polyclonal antibodies to rat-B-50. The Western blots show that the Mabs
      NM1, NM4, and NM6 recognize specifically the B-50 of bovine, human, and rat brain
      extract and the purified PKC phosphorylated and unphosphorylated rat B-50
      isoforms. The Mabs NM2 and NM3 cross-react with bovine B-50 immunoreactive c
      kinase substrate (BICKS), a protein sharing a 17 amino acid sequence homology
      with B-50. Two Mabs are useful for the detection of B-50 immunoreactivity in
      formalin-fixed human and rat brain tissues. In human specimen of the hippocampus,
      a characteristic neuropil distribution of B-50 is detected by the Mabs. In human
      muscle, Mabs reveal B-50 in nerve bundles and in axons at motor end plates. Thus,
      these Mabs are useful in investigating the function and localization of the B-50
      protein.

PMID- 1385625
TI  - Postural changes in dental hygienists. Four-year longitudinal study.
AB  - Numerous surveys identify the occurrence of musculoskeletal complaints as a
      concern in dentistry. However, no longitudinal data exist to indicate whether
      postural changes occur as a result of practicing dental hygiene. The purpose of
      this preliminary, four-year longitudinal study was to investigate whether any
      postural changes developed during the hygienists' clinical education and/or
      during subsequent dental hygiene practice after one and/or two years. It was
      anticipated that the awkward positions and intense physical demands placed on
      hygienists might initiate musculoskeletal problems, but that no postural changes
      would occur over this short period of time. Nine of 10 dental hygienists in the
      graduating class of 1987 were surveyed for existing musculoskeletal complaints,
      and the subjects were photographed for a measurement of postural change.
      Responses from participants indicated an increase in musculoskeletal-related
      complaints in each of the six areas investigated. The photographic findings
      indicated that one of the nine hygienists showed an increase in forward head
      posture, a postural change.

PMID- 1385624
TI  - Kynurenic acid concentrations are reduced in Huntington's disease cerebral
      cortex.
AB  - Huntington's disease (HD) is characterized by gradually evolving selective
      neuronal death. Several lines of evidence suggest that an excitotoxic mechanism
      may play a role. Tryptophan metabolism leads to production of quinolinic acid, an
      N-methyl-D-aspartate (NMDA) receptor agonist, and to kynurenic acid, an
      antagonist at these same receptors. We recently found increased kynurenine to
      kynurenic acid ratios in HD postmortem putamen and decreased kynurenic acid
      concentrations in cerebrospinal fluid, consistent with decreased formation of
      kynurenic acid in HD brain. In the present study we used HPLC with 16 sensor
      coulometric electrochemical detection to measure kynurenic acid and 18 other
      electrochemically active compounds in 6 cortical regions, caudate and cerebellum
      from controls, HD, Alzheimer's disease (AD), and Parkinson's disease (PD)
      patients. Significant reductions in kynurenic acid concentrations were found in 5
      of 6 cortical regions examined. Smaller reductions of kynurenic acid in the
      caudate, cerebellum and frontal pole were not significant. No significant
      reductions were found in the AD and PD patients. Both uric acid and glutathionine
      were significantly reduced in several regions of HD cerebral cortex, which could
      signify abnormal energy metabolism in HD. Since kynurenic acid is an antagonist
      of excitatory amino acid receptors, a deficiency could contribute to the
      pathogenesis of neuronal degeneration in HD.

PMID- 1385626
TI  - Presence of dopamine D1 receptors and absence of dopamine D2 receptors in human
      cerebral meningioma tissue.
AB  - Preliminary studies have shown that the dopamine D1 receptor is expressed in
      cerebral meningioma tissue. The current study presents evidence that the
      iodinated dopamine D1 antagonist [125I]SCH-23982 bound to dopamine binding sites
      in 33 of the 45 human cerebral meningiomas examined for this. Saturation curves
      and the linearity of the Scatchard analysis indicate that [125]SCH-23982 binds to
      a homogeneous population of binding sites. Competition curves reveal the presence
      of a dopamine D1 receptor by rank order of various dopaminergic and
      nondopaminergic antagonists ((+)-SCH-23390 greater than (+/-)-SKF-83566 greater
      than (cis)-flupentixol greater than (+)-butaclamol greater than chlorpromazine
      greater than 1-sulpiride greater than mianserin greater than (-)-butaclamol).
      Stereoselectivity was evaluated by (+)- and (-)-butaclamol. The mean (+/-
      standard deviation) dissociation rate constant was 369 +/- 196 pM with a density
      of 31.9 +/- 12.5 fmol/mg membrane protein among 33 meningiomas. The dopamine D2
      receptor was not present in the 30 meningiomas examined for this. These findings
      indicate that the dopamine D1 receptor identified is expressed alone and is
      therefore regulated independent of a D2 receptor in cerebral meningioma tissue.
      Although the function of the dopamine D1 receptor in cerebral meningiomas has not
      so far been defined, previous studies have suggested that the D1 receptor might
      be involved in the control of proliferative growth of meningiomatous tissue.

PMID- 1385628
TI  - Tissue-specific mosaicism for trisomy 21 and congenital heart disease.
AB  - Cytogenetic studies in a girl with ventricular septal defect and mosaicism for
      trisomy 21 showed that trisomy was present in most cells from the myocardium and
      lung but in only a minority from the skin and lymphocytes. These findings
      emphasize the importance of tissue-specific mosaicism as a cause of certain
      cardiovascular diseases.

PMID- 1385627
TI  - Dextromethorphan and high-dose benzoate therapy for nonketotic hyperglycinemia in
      an infant.
AB  - To test the hypothesis that nonketotic hyperglycinemia causes overstimulation of
      the excitatory N-methyl-D-aspartate receptor by allosteric glycine activation,
      and that reduction of glycine and blocking of the cation channel coupled to the
      receptor would be beneficial, we administered benzoate and dextromethorphan, a
      blocker of the N-methyl-D-aspartate channel to an infant with nonketotic
      hyperglycinemia. Therapy with benzoate, 500 mg/kg per day, was started on day 5,
      and the dosage was increased to 750 mg/kg per day on day 8, with prompt
      normalization of the neurologic and electroencephalographic findings. The glycine
      concentrations in both plasma and cerebrospinal fluid were substantially reduced.
      Dextromethorphan was added to the regimen on day 12. The electroencephalogram
      remained normal until the infant was 8 months of age, when diffuse slowing became
      apparent. Serial brain magnetic resonance imaging showed delayed myelination. At
      12 months of age, physical examination findings and growth were normal except for
      hypotonia. The developmental quotient was approximately 60, and the child was
      free of seizures. This outcome, although not ideal, is better than that typical
      for nonketotic hyperglycinemia. Our results suggest that trials with additional
      patients and other N-methyl-D-aspartate cation channel blockers are warranted.

PMID- 1385629
TI  - Association between increased atrial natriuretic peptide and reduced cisplatin
      nephrotoxicity in rats.
AB  - Plasma atrial natriuretic peptide (ANP) concentrations were monitored in two
      experimental models of protection from cisplatin nephrotoxicity. Sprague-Dawley
      rats made diabetic with streptozotocin (65 mg/kg) were protected from cisplatin
      induced nephrotoxicity when compared to control rats as indicated by reduced
      plasma creatinine (0.49 +/- 0.02 vs. 0.9 +/- 0.06 mg/dl; P less than .001) and
      blood urea nitrogen concentrations (18.51 +/- 1.4 vs. 43.08 +/- 2.1 mg/dl; P less
      than .001). Plasma ANP was also increased with experimental diabetes (76.5 +/-
      8.98 fmol/ml) vs. normoglycemic controls (43.8 +/- 8.9 fmol/ml; P less than .02).
      When diabetic rats were treated with insulin, the renal protection observed with
      the diabetic state was reversed (creatinine, 0.70 +/- .05 mg/dl); plasma ANP
      concentrations were also reduced (52.2 +/- 15.2 fmol/ml). Renal platinum
      concentrations were significantly lower in the diabetic group and the reversal of
      diabetic-induced renal protection with insulin was associated with increased
      renal platinum concentrations. In rats given a single i.p. dose of cisplatin (5
      mg/kg), a reduction in cisplatin-induced nephrotoxicity was observed when 5% NaCl
      was the vehicle of choice compared to that seen in rats given the same dose of
      drug in 0.9% saline (creatinine, 0.43 +/- 0.07 with 5% NaCl vs. 0.63 +/- 0.03
      with 0.09% NaCl). NaCl (5%) administration also resulted in increased plasma ANP
      concentrations when compared to rats receiving equivalent volumes of 0.9% NaCl
      (88.4 +/- 6.2 vs. 50.5 +/- 5.6 fmol/ml, respectively). These data suggest that
      increased endogenous ANP may be a mechanism of renal protection common to both
      experimental diabetes and hypertonic saline administration. Chronically increased
      ANP may prevent renal accumulation of platinum in the kidney.

PMID- 1385630
TI  - Potentiation of brain natriuretic peptides by SQ 28,603, an inhibitor of neutral
      endopeptidase 3.4.24.11, in monkeys and rats.
AB  - The depressor, natriuretic and cyclic GMP responses to several species of brain
      natriuretic peptide (BNP) were compared to atrial natriuretic peptide (ANP) 99
      126 in conscious spontaneously hypertensive rats (SHR) and in conscious
      cynomolgus monkeys treated with vehicle or the selective neutral endopeptidase
      (NEP 3.4.24.11) inhibitor N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta-
      alanine (SQ 28,603). In the conscious SHR, the natriuretic and cyclic GMP
      responses to 3 nmol/kg i.v. rat BNP-32 greater than rat ANP 99-126 greater than
      pig BNP-26 and were significantly potentiated by 100 mumol/kg i.v. SQ 28,603.
      Human BNP-32 was inactive in the SHR treated with either vehicle or SQ 28,603. In
      contrast, 1 nmol/kg i.v. of human BNP-32 stimulated renal and depressor responses
      in the conscious monkeys that were greater than or equal to those elicited by
      human ANP 99-126, whereas 3 nmol/kg i.v. rat BNP-32 reduced mean arterial
      pressure without affecting renal function. Furthermore, SQ 28,603 (100 mumol/kg,
      i.v.) significantly enhanced the cumulative losses of sodium and cyclic GMP
      stimulated by each of these peptides. In conclusion, the renal and depressor
      activities of BNP are highly species specific and are significantly potentiated
      by an inhibitor of NEP 3.4.24.11 in conscious SHR and monkeys. Therefore,
      protection of endogenous BNP may contribute importantly to the activity of NEP
      3.4.24.11 inhibitors in cardiorenal disorders such as hypertension and congestive
      heart failure.

PMID- 1385632
TI  - "Where dreams come true".

PMID- 1385631
TI  - The iron uptake mechanisms of enteropathogenic Escherichia coli: the use of haem
      and haemoglobin during growth in an iron-limited environment.
AB  - The iron uptake mechanisms of enteropathogenic Escherichia coli (EPEC) were
      examined and compared with those of control E. coli strains. The incidence of
      aerobactin production was similar (39% and 37% respectively) in the two groups.
      The quantities of enterochelin produced by aerobactin-negative EPEC and control
      strains were similar, as were the quantities of enterochelin produced by
      aerobactin-positive EPEC and control strains. The ability to use haem or
      haemoglobin as an iron source in an iron-restricted environment was found in
      80.4% and 60.8% of EPEC strains respectively, and in 76.6% and 56.6% of control
      E. coli strains. The ability of E. coli strains to use these compounds was not
      related to the production of enterochelin or aerobactin or to the production of
      haemolysins, and may be an important characteristic of bowel organisms. When
      growing in an iron-limited environment, the iron contained in haemoglobin was
      used in preference to ovotransferrin-bound iron. During periods of haemoglobin
      stimulated growth, the enterochelin uptake system was shown to be fully expressed
      and may be involved in transport of haemoglobin-derived iron into the cell.
      Uptake of ovotransferrin-bound iron took place immediately upon exhaustion of
      haemoglobin-derived iron. The ability to use iron derived from haem compounds
      represents an alternative iron uptake mechanism for organisms growing in an iron
      limited environment and allows greater flexibility during growth in vivo.

PMID- 1385633
TI  - Regulation of the nucleotide dependence of the cardiac sarcolemma Ca(2+)-ATPase.
AB  - The nucleotide dependence of the Ca(2+)-ATPase purified from cardiac sarcolemma
      by calmodulin-affinity chromatography was investigated for preparations either in
      the basal state or activated by three procedures: (i) addition of calmodulin;
      (ii) addition of phosphatidylserine and (iii) controlled proteolysis. Upon
      activation, the maximal velocity of ATP hydrolysis increases by a factor of 4-5,
      while the curves of ATP dependence of ATP hydrolysis change from hyperbolic to
      biphasic, revealing the presence of two Kmapp for ATP. A tight coupling between
      Ca2+ and ATP binding sites was also observed. At high ATP concentration, the
      ATPase activity of the basal state shows a complex dependence on Ca2+
      concentration, increasing sharply at millimolar Ca2+. Our results indicate that
      this increase in ATPase activity is paralleled by the appearance of a second, low
      affinity Kmapp for ATP. When only the high affinity site for ATP is occupied the
      ATPase activity of the basal state displays a simple, hyperbolic dependence on
      the Ca2+ concentration. In addition, increasing Ca2+ concentration appears to
      decrease the ATP binding at the low affinity site of the enzyme. The effect of
      ADP on ATP hydrolysis was also examined. The finding that ADP is a potent
      inhibitor of the purified Ca(2+)-ATPase from heart suggests that the stimulatory
      action of ADP observed in cardiac sarcolemmal vesicles is not an intrinsic
      property of the enzyme.

PMID- 1385634
TI  - [Atrial natriuretic peptide and plasma renin activity in patients with stable
      chronic obstructive pulmonary disease].
AB  - The relationship between plasma atrial natriuretic peptide (ANP) and plasma renin
      activity (PRA) was examined in patients with stable chronic obstructive pulmonary
      disease (COPD, n = 17). The plasma ANP level in patients was approximately twice
      that in normal subjects. A reciprocal relationship between ANP and PRA was shown
      in normal subjects; however, this relationship was not observed in COPD. Plasma
      ANP levels inversely correlated with PaO2, and tended to inversely correlate with
      angiotensin converting enzyme activity in serum. These results demonstrate that
      patients with COPD have higher plasma ANP concentration, and that ANP and PRA are
      not reciprocally related in stable COPD.

PMID- 1385635
TI  - Postcesarean endometritis: a brief review and comparison of three antibiotic
      regimens.
AB  - Three different antibiotic regimens (trospectomycin plus azteonam, clindamycin
      plus azteonam, and triple antibiotics-ampicillin plus clindamycin plus
      gentamicin) were all effective in treating patients with postcesarean
      endometritis. Patients are frequently cured clinically despite the fact that the
      offending organisms may be isolated in post-treatment cultures. Treatment of
      postcesarean endometritis without obtaining endometrial cultures is acceptable
      gynecologic practice. Obtaining post-treatment cultures is clearly not cost
      effective nor clinically beneficial. Drug treatment efficacy should be evaluated
      by clinical response. This communication is the first to report the new
      antibiotic, trospectomycin, in the treatment of postcesarean endometritis.
      Further clinical trials are currently underway.

PMID- 1385636
TI  - Rare point mutation at codon 301 and 969 of FMS/M-CSF receptor in acute
      myelomonocytic and monocytic leukemia.
AB  - We have investigated whether point mutations occurred at codon 301 or 969 of FMS
      (M-CSF receptor) in 19 patients with acute myelomonocytic (M4) and monocytic
      leukemia (M5). Nineteen peripheral blood and bone marrow blood samples collected
      from M4 and M5 patients were examined by using polymerase chain reaction and
      hybridization to allele specific oligonucleotide probes. Mutations at codon 301
      and 969 of FMS were not detected in any samples. FMS gene mutations at codon 301
      and 969 were rarely involved in M4 and M5 patients in Japan.

PMID- 1385637
TI  - Transient abnormal myelopoiesis in Down's syndrome--are some of them truly
      leukaemic?

PMID- 1385638
TI  - Pediatric leukemia/lymphoma with t(8;14)(q24;q11).
AB  - A variety of chromosomal translocations occur in pediatric T-cell acute
      lymphoblastic leukemia (T-ALL) in which a cellular oncogene or growth-related
      gene is translocated to the alpha/delta locus of the T-cell receptor gene. The
      t(8;14)(q24;q11) has been described at the cytogenetic and molecular level, but
      the disease associated with this translocation has not been defined clinically.
      Fifteen pediatric cases of leukemia/lymphoma with a t(8;14)(q24;q11) chromosomal
      translocation were collected from previous publications and institutional
      records. The estimated prevalence of this abnormality among all cases of ALL was
      1%. The t(8;14)(q24;q11) disease was characterized by male predominance (10/15),
      a median age of 5.5 years (range 1.8-17 years), high white blood cell count
      (median 95 x 10(9)/l), central nervous system infiltration (4/11), bulky
      extramedullary leukemia (10/11), and T-cell immunophenotype (12/15). The median
      event-free survival was 4 months, and the median survival, 11 months. Seven cell
      lines with t(8;14)(q24;q11) were established from six of the cases; four were T
      lymphoblastic, one was T-lymphoblastic, but expressed myeloid-related antigens,
      and two were predominantly myeloid. t(8;14)(q24;q11) leukemia/lymphoma and other
      ALLs involving 13(q11) have in common a high tumor burden, early spread to
      extramedullary sites, a propensity to form T-lymphoblastic or T-myeloid cell
      lines and, usually, an aggressive clinical course.

PMID- 1385639
TI  - Expression of M-CSF and its receptor (C-FMS) during factor-independent cell line
      evolution from hematopoietic progenitor cells cocultivated with gamma irradiated
      marrow stromal cell lines.
AB  - Gamma irradiation of plateau-phase clonal bone marrow stromal cell lines produces
      factor-independent growth of cocultivated clonal interleukin-3/granulocyte
      macrophage colony-stimulating factor-dependent hematopoietic progenitor cell
      lines. The process is associated with three biologic changes including: (i)
      adherence of hematopoietic cells to stromal cells forming 'cobblestone islands';
      (ii) an intermediate stage [during which the cells show proliferation in
      suspension in the presence in leukemogenic stromal factor (LSF), a factor similar
      to macrophage colony-stimulating factor (M-CSF) released by irradiated stromal
      cells, and transient hematopoietic cell surface expression of MAC-1, and c-fms (M
      CSF receptor)]; and (iii) a third stage of factor-independence. A monoclonal
      antibody to M-CSF receptor inhibited proliferation of intermediate stage but not
      all factor-independent cell subclones. In the present studies, a subclonal factor
      independent malignant subline of FDC-P1JL26 derived by cocultivation with gamma
      irradiated stromal cells as well as the parent clone and intermediate stage cells
      were shown to express significant levels of M-CSF polyA+ mRNA and M-CSF of at
      least two sizes (23 and 15 kDa) as detected by 35S-methionine labelling and
      immunoprecipitation with polyclonal anti-M-CSF antiserum. There was no
      significant difference in intracellular M-CSF protein size between cells at each
      of the three stages of biologic change. This M-CSF was not detected on the cell
      surface by fluorescence-activated cell sorting (FACS). In contrast, c-fms
      expression at the cell surface was detected by FACS analysis and c-fms polyA+
      mRNA was only detected during the intermediate stage of induction of factor
      independence. FDC-P1JL26 parent cells, the subclone stimulated by LSF, and the
      factor-independent subclone, showed little or no detectable autophosphorylation
      of the c-fms receptor at tyrosine. There was no detectable rearrangement of the M
      CSF or c-fms genes by Southern analysis between clonal lines during the three
      stages. While we cannot rule out an autocrine mechanism or mutated c-fms receptor
      mechanism, the data also suggest that evolution of hemopoietic cell factor
      independence during cocultivation with irradiated stromal cells may involve a
      mechanism distal to the c-fms receptor/M-CSF interaction.

PMID- 1385640
TI  - Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac
      hypertrophy and the tissue angiotensin II content in spontaneously hypertensive
      rats.
AB  - Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor
      antagonist, was administered orally to 10-week-old spontaneously hypertensive
      rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin
      activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per
      day) lowered blood pressure markedly. Losartan reduced significantly the left
      ventricular weight by 11% compared with control rats. The left ventricular Ang II
      content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue,
      control, p less than 0.05), whereas PRA and plasma Ang II concentration were
      increased by the treatment. With the control and Losartan-treated animals, there
      was a significant positive correlation between the left ventricular weight and
      the tissue Ang II content (r = 0.563, p less than 0.05). These results provide
      evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an
      important role in the pathophysiology of left ventricular hypertrophy of this
      animal model of human hypertension.

PMID- 1385641
TI  - Early recovery from laparoscopic repair of hiatus hernia.

PMID- 1385643
TI  - Laparoscopic splenectomy with an ultrasonic dissector.

PMID- 1385642
TI  - Impairment of contractile response to carbachol and muscarinic receptor coupling
      in gastric antral smooth muscle cells isolated from diabetic streptozotocin
      treated rats and db/db mice.
AB  - This work explored the role of the cholinergic pathway, assessed at a post
      synaptic level by the use of isolated smooth muscle cells, in the impairment of
      antral motility associated with diabetic gastroparesis. Contractile response to
      carbachol--but not to erythromycin, a motilin receptor agonist--was abolished in
      antral smooth muscle cells isolated from (i) rats previously rendered diabetic by
      a single i.v. dose of streptozotocin (STZ, 60 mg/kg) and (ii) db/db spontaneously
      diabetic mice. Insulin treatment of STZ-rats was able to prevent the impairment
      of the carbachol contractile response, but not to reverse it once established. In
      STZ-rats, impairment of contractile response was not associated with a change in
      density of [3H]-N-methyl-scopolamine ([3H]-NMS) binding sites (approximately 1.5
      fmol/mg protein). Displacement curve of the [3H]-NMS binding by carbachol was
      shifted to the right in diabetic rats as compared to controls. The addition of
      GTP-gamma-S induced a shift to the right of the displacement curve in control but
      not in diabetic animals. These results strongly suggest that diabetes is
      associated with an early and specific alteration of the muscarinic control of
      contraction of antral smooth muscles at a post-synaptic level, associated with an
      alteration of the GTP-binding proteins coupled to muscarinic receptors.

PMID- 1385644
TI  - Asthma drug therapy debate.

PMID- 1385645
TI  - Appendicitis: laparoscopic strategy in diagnosis and treatment.

PMID- 1385646
TI  - Effect of local injection of 8-OH-DPAT into the dorsal or median raphe nuclei on
      extracellular levels of serotonin in serotonergic projection areas in the rat
      brain.
AB  - Using in vivo microdialysis, we have examined the effects of local administration
      of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into either the dorsal
      (DRN) or the median (MRN) raphe nucleus on extracellular levels of serotonin (5
      HT) in the corresponding projection fields, namely striatum and ventral
      hippocampus in the anaesthetized rat. Local injection of 8-OH-DPAT (0.5
      microgram/0.1 microliter) in the DRN reduced extracellular 5-HT levels in the
      striatum (-55%) and to a lesser extent in the hippocampus (-22%). When injected
      at the same dose in the MRN, 8-OH-DPAT caused a marked decrease in 5-HT output in
      the hippocampus (-41%) and had no effect in the striatum. Autoradiographic
      studies performed on brains from animals that received a local injection of [8H]8
      OH-DPAT into either the DRN or MRN under similar experimental conditions
      indicated that the radioactivity remained localized within each midbrain raphe
      nucleus. These results confirm anatomical data demonstrating that the striatum
      and the ventral hippocampus receive their serotonergic innervation preferentially
      from the DRN and the MRN, respectively.

PMID- 1385647
TI  - B-50/GAP43 localization on membranes of putative transport vesicles in the cell
      body, neurites and growth cones of cultured hippocampal neurons.
AB  - We conducted an electron microscopic immunocytochemical study to locate B
      50/GAP43 in various cellular elements of hippocampal neurons grown in dissociated
      cell culture. B-50 was detected with pre- and post-embedding immunoincubation,
      using affinity-purified B-50 antibodies and secondary antibodies coated on gold
      probes. For the first time ultrastructural evidence is presented for the location
      of B-50 on the membranes of electron-lucent transport vesicles with a diameter of
      99.4 +/- 2.9 nm, present in the trans region of the Golgi apparatus, in neurites
      and in growth cones of cultured hippocampal neurons.

PMID- 1385648
TI  - Larvicidal properties of macrophages induced by cloned murine schistosomal egg
      antigen-specific CD4 positive T-helper lymphocytes.
AB  - The role of T-helper (TH) lymphocytes in activating peritoneal macrophages (PM)
      to kill larvae of the helminth Schistosoma mansoni (schistosomula) was
      investigated with the use of egg antigen-specific CD4 positive TH clones of both
      the TH1 and TH2 types. Results showed that stimulated TH1 clones, in exceedingly
      small numbers, or supernatants thereof, conferred on PM the ability to kill
      schistosomula. The molecule responsible for PM activation was found to be
      interferon-gamma (IFN-gamma). IFN-gamma-induced PM larvicidal activity was
      dependent on live cells, energy, as well as protein synthesis, and appeared to be
      mediated by toxic nitrogen metabolites. In contrast, egg antigen-specific TH2
      clones, or their supernants, failed to induce PM larval killing, as they did not
      secrete IFN-gamma, or any equivalent macrophage activating factor. We postulate a
      mechanism by which egg antigen-specific TH1 clones may be capable of playing a
      critical role in the resistance to schistosomal reinfection through IFN-gamma
      mediated activation of macrophage helminthotoxicity.

PMID- 1385649
TI  - Issues and epidemiological evidence regarding radiation-induced thyroid cancer.
AB  - The available information on the induction of thyroid cancer in humans by
      ionizing radiation is summarized and weaknesses or gaps in assessing risk are
      identified. Issues to be addressed include: average estimates of thyroid cancer
      risk from external irradiation, the effects of age on thyroid cancer induction,
      shape of the dose-response curve for acute irradiation, magnitude of risk at low
      doses, effects of dose fractionation or dose protraction, the relative
      effectiveness of iodine-131 (131I) in inducing thyroid cancer compared to
      external radiation, the temporal course of radiogenic thyroid cancer risk,
      mortality caused by thyroid cancer, host-susceptibility factors for radiogenic
      thyroid cancer, and biological factors in risk. It is concluded that the most
      important needs are to obtain more information on thyroid cancer risks following
      low-level or highly fractionated radiation exposures and following 131I exposure
      in children.

PMID- 1385650
TI  - Nurse blows whistle: retaliatory termination? Case in point: Wright v. Shriners
      Hospital (589 N.E. 2d 1241--MA [1992]).

PMID- 1385651
TI  - Legal case briefs for nurses. MN: comp. claimant's "late report" excluded:
      admissibility of evidence issue; IL: nursing home settles sexual assault case:
      "confidentiality of settlement" issue.

PMID- 1385652
TI  - [The diagnostic use of laparoscopy in liver pathology in light of the evolution
      of imaging diagnosis].
AB  - We considered 87 patients suffering from chronic hepatic pathology. 62 patients
      have resulted suffering from cirrhosis or chronic active hepatitis, 25 from
      neoplasias. In the patient's group with chronic liver disease the humoral tests
      were not able to differentiate between cirrhosis or chronic active hepatitis. In
      the present retrospective experience echography showed sensibility 0.53 and
      specificity 0.91. In cirrhosis group, sensibility 0.5 and specificity 0.60 in
      chronic active hepatitis, sensibility 0.8 and specificity 0.95 in the neoplasia
      group. Peritoneoscopy showed sensibility 0.97 and specificity 0.93 in the
      cirrhosis group and sensibility 0.90 and specificity 1.00 in the neoplasia group.
      We had one case of major complication: hemoperitoneum from tear of adhesion
      secondary to previous laparotomy. We can conclude that peritoneoscopy is an
      useful procedure in the study of liver chronic disease and it still finds
      indication in selected cases of focal illness.

PMID- 1385653
TI  - Binding of human alpha-interferon in the brain tissue membranes of rat.
AB  - The receptor binding characteristics of human lymphoblastoid alpha-interferon
      (IFN) to human Daudi cell line was compared with its binding to membrane
      homogenates derived from various regions of rat brain. Rat brain membranes bound
      specifically a detectable amount of I-125 alpha interferon revealing the receptor
      affinity constant (Kd) of 3.9-4.2 x 10(-10) M and the Bmax was 0.9-1.7 fmoles/mg
      wet weight tissue depending on the analyzed brain region (the highest Bmax was
      obtained in the membranes from the hypothalamus region, the lowest one from the
      spinal cord membranes).

PMID- 1385654
TI  - Cholelithiasis associated with medroxyprogesterone acetate therapy in men.
AB  - Five out of forty-five adult men, 50 years of age or less, who had received, for
      at least six months, medroxyprogesterone acetate (MPA, Depo Provera) IM, 200-400
      mg/week, for prevention of sex-offending or genital-mutilating behavior developed
      symptomatic cholelithiasis. Thirty of these men were studied with gallbladder
      ultrasound prospectively off MPA and at six-month intervals while taking the
      medication and then six months off MPA. Gallstones recovered from two patients
      were found to have very high cholesterol content, suggesting they were formed in
      cholesterol supersaturated bile. These findings are consistent with the increased
      incidence of gallbladder disease related to high-progesterone states and suggest
      that MPA may be a causative agent in cholelithiasis. The physiologic studies on
      gallbladder contraction and cholecystokinin release in a subset of the patients
      failed to provide information on a mechanism for the possible increased incidence
      of gallbladder disease.

PMID- 1385655
TI  - [Current role of laparoscopy in the diagnosis and treatment of ovarian cysts].
AB  - Between October 1986 and March 1990, 220 patients underwent surgical treatment
      for ovarian cysts. 156 of these patients underwent an initial celioscopy and
      could potentially benefit from celiosciopic treatment. The group mean age was
      33.3 years. The circumstances under which the cysts were discovered usually
      consisted of pelvic pain or diagnosis during a routine examination. Twenty-four
      patients underwent laparotomy immediately after coelioscopy either due to a
      suspect macroscopic diagnosis either due to technical difficulties. 84.6 percent
      of the patients in the group were able to undergo celioscopic treatment only,
      essentially consisting of intraperitoneal cystectomy. The main advantages were
      the reduction in adherent sequelae in these women of a sexually active age, but
      also some financial savings related to the reduced duration of hospitalization
      and of sick leave. The theoretical reservations consist of the risk of malignancy
      and macroscopic diagnosis following coelioscopic exploration must be very
      restricted, with laparotomy whenever there is any doubt. No malignant tumor was
      escaped detection in this group.

PMID- 1385656
TI  - Changes in the expression of the tumor-associated antigen recognized by
      monoclonal antibody 44-3A6 in A549 cells due to calcium.
AB  - Although there is extensive data available on Ca2+ effects in normal tissues,
      comparatively little is known about its effects or regulation in tumor cells. The
      present studies were undertaken to investigate whether various extracellular
      calcium concentrations could modulate the expression of the tumor-associated
      antigen (TAA) recognized by monoclonal antibody (MAb) 44-3A6. It is highly
      expressed by the human lung adenocarcinoma cell line A549 and has been shown to
      be a 40-kD integral plasma membrane protein. Treatment of the A549 cell line with
      various concentrations of exogenous calcium showed a dose-dependent rise in the
      internal free calcium levels up to 2.4-2.9 mM (external calcium treatment). At
      higher concentrations, the internal calcium level showed a decline, indicating a
      higher calcium efflux. The calmodulin-dependent Ca(2+)-ATPase enzyme involved in
      calcium homeostasis was assayed under these same conditions. The enzyme activity
      increased with increasing external calcium concentrations showing a 5-fold
      increase in cells treated with 4.05 mM calcium. These data suggest that as the
      internal calcium approaches toxic levels, the Ca(2+)-regulated ATPase activity
      increases to reduce the calcium overload within the cell. Employing Western blot
      analysis and immunoperoxidase staining studies, this report shows that the
      antigen recognized by MAb 44-3A5 on A549 cells increased with an increase in
      calcium concentration. Evidence that this antigen is phosphorylated is presented
      using Western blot analysis of a radiolabeled antigen-enriched plasma membrane
      fraction. The previously reported subcellular localization, and now the
      phosphorylation and responsiveness to calcium by this TAA, gives it the
      properties predicted to be seen in a calcium 'pump-like' molecule. Thus, these
      studies support the hypothesis that this TAA may be important in intracellular
      calcium concentration control or that it is regulated via some calcium-mediated
      process.

PMID- 1385657
TI  - Predicting return to work for lower back pain patients receiving worker's
      compensation.
AB  - The results of a prospective study of 134 patients with lower back pain suggest
      that nonorganic factors are better predictors of return to work than organic
      findings. Patients who returned to work had fewer job, personal, or family
      related problems. There were no significant differences between patients who
      returned to work and those who did not when comparing myelograms, computed
      tomographic scans, or roentgenographs. The only significant difference in
      physical organic findings was for muscle atrophy. Patients who did not return to
      work had a statistically higher incidence rate of muscle atrophy. Length of time
      off from work was significantly related to outcome, but when patients were
      categorized according to time off the job, different factors predicted failure to
      return for patients off work for less than 6 months and patients off for more
      than 6 months. For patients off for less than 6 months, important predictors were
      a high Oswestry score, history of leg pain, family relocation, short tenure on
      the job, verbal magnification of pain, reports of moderate to severe pain on
      superficial palpation, and positive reaction to a "sham" sciatic tension test.
      None of these was a significant predictor for the group off for more than 6
      months. For the group off work for more than 6 months, previous injuries, and
      stability of family living arrangements were among the significant predictors not
      significant for the group off less than 6 months. Using 21 factors selected from
      a larger group of 92 factors, three statistically significant (P less than or
      equal to 0.001) predictive measures were developed. These measures predicted
      return to work for the total sample, and for the two subgroups (off more than, or
      less than 6 months) more accurately than did the total set of 92 factors.

PMID- 1385658
TI  - Mobility, strength, and fitness after a graded activity program for patients with
      subacute low back pain. A randomized prospective clinical study with a behavioral
      therapy approach.
AB  - Patients with nonspecific mechanical low back pain (n = 103), examined by an
      orthopaedic surgeon and a social worker, were randomized to an activity group (n
      = 51) and a control group (n = 52). Patients with defined orthopaedic, medical,
      or psychiatric diagnoses were excluded before randomization. No patients were
      excluded due to place of birth or difficulties in speaking or understanding the
      Swedish language. The purpose of the study was to compare mobility, strength and
      fitness after traditional care and after traditional care plus a graded activity
      program with a behavioral therapy approach. A graded activity program, with a
      behavioral therapy approach was given under the guidance of a physical therapist.
      The endpoint of the graded activity program was return to work. This program
      significantly increased mobility, strength, and fitness more than could be
      explained by only a time recovery effect, especially in males. The patients in
      the activity group returned to work earlier than did the patients in the control
      group. Spinal rotation, abdominal muscle endurance time and lifting capacity were
      significantly correlated to rate of return to work. Traditional care plus a
      graded activity program were superior to only traditional care, evaluated in
      terms of mobility, strength and fitness. The graded activity program proved to be
      a successful method of restoring occupational function and facilitating return to
      work in subacute low back pain patients. The patients in the graded activity
      program learned that it is safe to move, while regaining function.

PMID- 1385659
TI  - Serial lumbar dynamometry in low back pain.
AB  - To determine the significance of changes in motor performance as measured by
      lumbar dynamometry, serial lumbar dynamometry was performed on a group of 45 male
      Workers' Compensation patients with chronic "mechanical" low back pain and in a
      group of 20 healthy male volunteers. The patients were men aged 20-60 years,
      whose current episode of low back pain had lasted for at least 3 months (mean
      19.5 weeks, range 12-47 weeks). Testing was performed at entry into a "back
      school" program of therapy and again 2 weeks and 4 weeks later. The control group
      showed a slight improvement in almost all variables of strength and range of
      motion between the first and second tests but no significant change between the
      second and third tests. This was consistent with a learning effect. The patient
      group was analyzed as a whole and also in two groups based on their response to
      the Waddell maneuvers at entry: Waddell score 0-2 (no excessive illness behavior)
      and 3-5 (excessive illness behavior). As a whole, the patients showed significant
      progressive improvement in most variables on successive tests. The group with the
      low Waddell score had significantly greater strength and range of motion than the
      group with the high Waddell score but the trend of improvement with time was
      similar in the two groups. The authors conclude that in this sample of patients
      with low back pain, serial lumbar dynamometry reveals a progressive improvement
      in performance, which is greater than the improvement expected from the natural
      history of physical recovery and greater than the improvement expected from an
      increase in strength and range of motion attributable to the therapeutic
      exercises performed and is much larger than any learning effect related to the
      test procedure.

PMID- 1385660
TI  - Low back and neck/shoulder pain in construction workers: occupational workload
      and psychosocial risk factors. Part 1: Relationship to low back pain.
AB  - The prevalence rate of musculoskeletal problems, especially low back pain and
      severe low back pain in a randomly selected sample of 1,773 construction workers
      was studied. Its relationship to physical and psychosocial factors was analyzed.
      The workers answered a postal questionnaire. Workload was measured by means of
      eight manual materials handling indices and ten psychosocial indices, based on
      results from factor analyses. The 1-year prevalence rate of low back pain was 54%
      and of severe low back pain 7%. The relationship to heavy manual materials
      handling differed with age in such a manner that it could be interpreted as a
      healthy worker effect. Between severe low back pain and both stooping or kneeling
      a dose-response relationship was found. The most prominent of the psychosocial
      factors associated with low back pain and severe low back pain were the stress
      index and the psychosomatic and psychic indices. The age-standardized prevalence
      rate ratio of low back pain was 1.6 (95% confidence interval 1.4-1.8) and for
      severe low back pain 3.1 (95% confidence interval 2.3-4), when workers reporting
      "high" stress were compared to workers reporting "low" stress.

PMID- 1385661
TI  - Low back and neck/shoulder pain in construction workers: occupational workload
      and psychosocial risk factors. Part 2: Relationship to neck and shoulder pain.
AB  - The prevalence rate of neck and shoulder trouble and considerable neck and
      shoulder pain in a randomly selected sample of 1773 construction workers were
      studied. The relationship to physical and psychosocial factors was analyzed. The
      workers answered a postal questionnaire. Workload was measured by means of eight
      manual materials handling indices and ten psychosocial indices, based on results
      from factor analyses. The 1-year prevalence rate of considerable neck and
      shoulder trouble was 56% and of neck and shoulder pain 12%. To work with hands
      above shoulder level showed a dose-response relationship to both neck and
      shoulder trouble and neck and shoulder pain. The psychosocial factors were more
      prominently associated with neck and shoulder trouble and neck and shoulder pain
      than the physical workload factors. The psychosocial indices; psychosomatic and
      psychic symptoms, stress and job satisfaction showed the highest age-standardized
      prevalence rate ratios for both neck and shoulder trouble and neck and shoulder
      pain.

PMID- 1385662
TI  - Chronic cocaine enhances serotonin autoregulation and serotonin uptake binding.
AB  - Repeated cocaine intoxication can result in the development of behavioral
      sensitization in animals and psychosis in humans, phenomena that have been
      associated with alterations in dopamine (DA) function. Using electrophysiologic
      and autoradiographic techniques, modifications of central serotonin (5
      hydroxytryptamine; 5-HT) systems were investigated in rats treated with a regimen
      of cocaine administration that produced behavioral sensitization. The inhibitory
      response of single 5-HT neurons in the dorsal raphe (DR) to (-)-cocaine, the 5-HT
      uptake inhibitor fluoxetine or the 5-HT1A agonist 8-hydroxy-2-[di-N
      propylamino]tetralin (8-OHDPAT) was significantly enhanced in cocaine-treated
      rats. Furthermore, several brain areas that contain either cell bodies (DR) or
      terminals for 5-HT (medial and sulcal prefrontal cortex, frontal cortex) showed
      cocaine-induced elevations in [3H]imipramine-labeled 5-HT uptake sites, while
      [3H]-8-OHDPAT-labeled 5-HT1A receptors were decreased only in the central medial
      amygdala. These results suggest that modifications of autoregulatory mechanisms
      secondary to alterations of 5-HT uptake processes may contribute to the
      development of cocaine sensitization.

PMID- 1385663
TI  - [123/125I]RTI-55, an in vivo label for the serotonin transporter.
AB  - [123I]RTI-55, an iodinated derivative of the cocaine analog 3 beta-phenyltropane
      2 beta-carboxylic acid methyl ester, was evaluated as an agent for in vivo
      labeling of the serotonin transporter. Labeling of the precursor of RTI-55 with I
      123 was efficient and yielded a high specific activity product. After intravenous
      injection of [123I]RTI-55 into rats, the tracer accumulated in regions with high
      densities of serotonin and dopamine uptake sites. The distribution of [123I]RTI
      55 binding in areas rich in serotonin uptake sites correlated with [3H]serotonin
      uptake measured in vitro in the same regions. Specific [123I]RTI-55 binding to
      serotonin uptake sites was inhibited by paroxetine but not by GBR 12,909.
      Treatment of rats with neurotoxic doses of fenfluramine caused decreases of 66%
      (in the hypothalamus) to 83% (in the superior colliculi) of specific [125I]RTI-55
      binding in all areas except in the striatum and the olfactory tubercles (regions
      rich in dopamine transporters). These results indicate that [123/125I]RTI-55
      binds, although not selectively, to the serotonin transporter in vivo.
      Furthermore, they suggest that [123I]RTI-55 holds promise as a SPECT imaging
      agent for the study of the serotonin transporter in humans in health and disease.

PMID- 1385664
TI  - Topographic nonoverlapping distribution of D1 and D2 dopamine receptors in the
      amygdaloid nuclear complex of the rat brain.
AB  - The distribution of D1 and D2 dopamine (DA) receptors in the nuclei and
      subnuclear zones of the rat amygdaloid complex was mapped using quantitative
      light microscopic autoradiography. [125I]iodosulpiride and [125I]SCH 23982 (in
      the presence of 50 nM ketanserin) were used to label D2 and D1 DA receptors,
      respectively. The DA receptor subtypes exhibited a topographic, nonoverlapping
      distribution which generally conformed to the cytoarchitectonic boundaries of the
      component nuclei and subnuclear zones of the amygdaloid complex. The highest
      density of [125I]iodosulpiride binding sites was observed in the main
      intercalated cell group and the central amygdaloid nucleus where a medial to
      lateral gradient of binding sites was localized to its subnuclear zones.
      [125I]SCH 23982 binding sites were localized in the main intercalated cell group
      and the basolateral amygdaloid nucleus with a uniform low density in the central
      nucleus. The functional topography of mesoamygdaloid DA neurons may therefore be
      mediated, in part, at the level of DA receptor subtypes. The pattern of
      distribution of [125I]iodosulpiride binding sites in subdivisions of the central
      amygdaloid nucleus and bed nucleus of the stria terminalis suggests that the
      functions of the "extended amygdala," a major system of the functional
      organization of the basal forebrain, may be regulated by DA afferents at multiple
      key sites of D2 receptor action.

PMID- 1385665
TI  - Identification of murine thymocyte populations capable of extensive proliferation
      in serially passaged thymic organ cultures.
AB  - Using the approach of titrating precursor cells into mouse thymus organ cultures
      and serial passage, we have sought to compare the proliferative capacities of
      cells derived from adult and embryonic thymus and related haemopoietic tissues.
      We find that cells derived from the liver and thymus of day 14 embryos are
      capable of extensive proliferation in such cultures (surviving for at least 12
      weeks) whereas cells derived from adult sources (blood and thymus) display a much
      more restricted lifespan and potential for division. Analysis of sequentially
      passaged thymic lobes shows that cells lacking CD4 and CD8 (CD4- and CD8-) and a
      subset of single CD8 positives are selectively expanded in these cultures. A
      preliminary study of the CD4-CD8- populations in these lobes suggest that these
      include cells expressing surface CD3 (in association with either TCR alpha beta
      or TCR gamma delta) and a subset of CD4-CD8-CD3-. These findings suggest that
      sequential passage of thymocytes in organ culture may be a useful alternative
      strategy for characterising cells with high proliferative potential, resident in
      the thymus and also for probing their lineage relationships.

PMID- 1385666
TI  - Observations on lymphomagenesis and lymphoma in AKR mice. A description of
      prelymphoma changes in the thymus and phenotypic diversity of lymphomas induced
      by SL3-3 virus.
AB  - These studies were designed to look for a correlation of intrathymic survival of
      virus-infected thymocytes with lymphomagenesis. Cells from the normal-appearing
      prelymphoma thymus of SL3-3 virus-treated AKR mice were studied. Also, phenotypic
      properties of the malignant cells from the virus-induced lymphomas are described.
      In this model system, 100% of mice inoculated with virus at three days of age
      develop thymic lymphoma between 60 and 90 days of age. The experiments show that
      cells with malignant potential do not appear in the thymus until 36 days after
      virus inoculation. These cells are initially thymus-dependent (TD) in that they
      produce lymphoma of donor-type in recipients after intrathymic inoculation with
      long latency. They do not produce lymphoma after subcutaneous inoculation in
      syngeneic hosts. At 39 days after virus inoculation, the first thymus independent
      (TI) lymphoma cells appear. These cells, like the cells isolated from thymi with
      overt tumors, produce lymphoma of donor-type after a short latency when
      inoculated by the intrathymic or subcutaneous route. Thymocytes from normal
      appearing thymi of mice at 42 days after virus inoculation, which could be
      expected to include TD, TI or no lymphoma cells, were evaluated for their ability
      to survive in a recipient thymus for three weeks after intrathymic inoculation.
      They were compared to thymocytes from age-matched control mice. Thymi receiving
      the virus-infected thymocytes showed 15% to 80% donor cells at three weeks. The
      highest numbers of donor cells were from thymi which were shown to contain TI
      lymphoma cells. However, cells from thymi with TD and no lymphoma cells could
      also be detected in significant numbers at three weeks after intrathymic
      inoculation. Less than 2% of donor-type thymocytes could be found after
      inoculation of thymocytes from normal control AKR mice. These data provide
      evidence that virus infection of thymocytes, even before the appearance of cells
      with lymphomagenic potential, endows them with a capacity for prolonged
      intrathymic survival. This appears to be a necessary step for tumor progression
      in this model. A remarkable phenotypic diversity of the virus-induced lymphomas
      was shown. The effect of various growth environments, intrathymic, subcutaneous,
      and in vitro on lymphoma cell phenotypic expression revealed individual
      differences in each tumor and in each environment.

PMID- 1385667
TI  - Experimental atrophic rhinitis in 2 and 4 month old pigs infected sequentially
      with Bordetella bronchiseptica and toxigenic type D Pasteurella multocida.
AB  - Experimental infections with Bordetella bronchiseptica and/or toxigenic type D
      Pasteurella multocida were studied in 2- and 4-month-old primary specific
      pathogen-free pigs. None of the 2-month-old pigs inoculated with B.
      bronchiseptica or P. multocida alone developed turbinate atrophy. All the pigs
      inoculated with B. bronchiseptica (10(7) CFU/head) and P. multocida (10(9)
      CFU/head for 5 consecutive days) together, however, developed clinical and post
      mortem signs of atrophic rhinitis (AR) similar to the naturally occurring
      disease. Slight to severe turbinate atrophy was observed in the 4-month-old pigs
      inoculated with B. bronchiseptica and P. multocida (at the same concentration as
      above) at necropsy.

PMID- 1385668
TI  - [Characteristics and results of the determination of the doses of internal
      irradiation of the thyroid gland in the population of contaminated districts of
      the Byelorussian Republic].
AB  - The authors provide the results of studying the reconstruction of individual
      doses of thyroid radiation among the community living in polluted areas of the
      Byelorussian Republic according to radiation monitoring data and with regard to
      the nature of radioactive pollution of the land. Every individual result of
      estimating the degree of thyroid radiation was characterized by 3 magnitudes: the
      lower and upper limit of possible values and by the intermediate (basic) value.
      The authors hold that studies of the correlations between the values of
      individual doses of thyroid radiation and different parameters of the radiation
      situation in every region will promote further specification of individual doses
      of thyroid radiation.

PMID- 1385669
TI  - [The mechanism of milk contamination in the territory of Gomel Oblast].
AB  - The authors provide the results of studying 137Cs and 90Sr pollution of soil,
      plants and milk in the Gomel region in 1986-1989. Describe the dynamics of the
      ratios soil-grass and milk-soil during that period. The content of 137Cs in milk
      ranged from n.10(-10) to n.10(-7) Ci/l in polluted regions and from n.10(-10)
      n.10(-9) Ci/l in the so-called pure regions. In all the regions examined, the
      concentration of 90Sr in milk was far lower than that of 137Cs. After the
      accident the levels of 137Cs in milk rose 18-350-fold and those of 90Sr 3-16-fold
      on the average in the regions. One can observe a progressive decrease of the
      ratios of accumulation in the grass-soil and milk-soil systems and a decline of
      the concentration of 137Cs and 90Sr in milk. However, the percentage of samples
      with an increase of the temporarily permissible in 1988 levels of cesium
      radionuclides was fairly high in 1989 in certain regions: in the Vetkovsk region,
      it was 35.3%, in the Chechersky region, it was 28.0%. During 1987-1989, the
      concentration of 90Sr in milk did not exceed 1 x 10(-9) Ci/l in the areas
      examined. The broad range of the indicators of milk pollution with 137Cs and 90Sr
      is specified by varying density of the area pollution, differences in the
      physicochemical status of radionuclides in accident fall-outs, and geochemical
      characteristics of the soil sheet.

PMID- 1385670
TI  - Left ventricular hypertrophy: an initial response to myocardial injury.
AB  - The prevailing wisdom generally has been that the failing heart hypertrophies in
      response to increased wall stress. The increase in myocardial mass observed in
      heart failure is therefore a relatively late compensatory event geared to
      normalize wall stress. Although this is undoubtedly true, especially for heart
      failure resulting from a large anterior myocardial infarction accompanied by
      rapid left ventricular expansion, it is possible that an important form of
      hypertrophy occurs much earlier as an initial response to myocardial injury. One
      can hypothesize that the initial response to injury is a nonspecific phenotypic
      alteration of the cardiac myocyte to one of growth and development. Such changes
      may be driven by both trophic and mechanical forces and may be important in
      altering the architecture of the myocardial cell and surrounding cardiac
      interstitium. Preliminary data from a variety of models support the concept that
      neuroendocrine activity is an important component in the ventricular remodeling
      process, and that pharmacologic interventions designed to block systemic and
      tissue neuroendocrine activity may prevent excessive cardiac enlargement and its
      ultimate consequences. Because this concept has important implications for
      preventive cardiology, the results of several prevention trials, including the
      Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS), Studies of
      Left Ventricular Dysfunction (SOLVD), and Survival and Ventricular Enlargement
      (SAVE) are awaited eagerly.

PMID- 1385671
TI  - Insulin-dependent diabetes mellitus in native Estonians and immigrants to
      Estonia.
AB  - The authors compared the epidemiology of childhood insulin-dependent diabetes
      mellitus in Estonia during 1980-1989 between native Estonians and an immigrant
      group that consisted mainly of Russians. The average annual incidence of diabetes
      mellitus was significantly higher in Estonians (11.8 per 100,000 children aged
      less than 15 years; 95% confidence interval (CI) 10.4-13.3) than in non-Estonians
      (7.6 per 100,000 children aged less than 15; 95% CI 6.2-9.4). This difference
      appeared in both sexes. The highest incidence in both Estonians and non-Estonians
      was recorded in 1982, when the incidence in the immigrant population was twice as
      high as the baseline level. These data indicate that immigrant populations need
      not acquire the same risk of insulin-dependent diabetes as the native population.

PMID- 1385673
TI  - Differences in vitamin D status between countries in young adults and the
      elderly.
AB  - PURPOSE: To compare vitamin D status between countries in young adults and in the
      elderly. MATERIALS AND METHODS: Reports on vitamin D status (as assessed by serum
      25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped
      according to geographic regions: North America (including Canada and the United
      States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and
      Central and Western Europe (including Belgium, France, Germany, Ireland, The
      Netherlands, Switzerland, and the United Kingdom). RESULTS: Vitamin D status
      varies with the season in young adults and in the elderly, and is lower during
      the winter in Europe than in both North America and Scandinavia. Oral vitamin D
      intake is lower in Europe than in both North America and Scandinavia.
      Hypovitaminosis D and related abnormalities in bone chemistry are most common in
      elderly residents in Europe but are reported in all elderly populations.
      CONCLUSIONS: The vitamin D status in young adults and the elderly varies widely
      with the country of residence. Adequate exposure to summer sunlight is the
      essential means to ample supply, but oral intake augmented by both fortification
      and supplementation is necessary to maintain baseline stores. All countries
      should adopt a fortification policy. It seems likely that the elderly would
      benefit additionally from a daily supplement of 10 micrograms of vitamin D.

PMID- 1385674
TI  - Back to (PACU) basics.

PMID- 1385672
TI  - The thrombotic diathesis associated with the presence of phospholipid antibodies
      may be due to low levels of free protein S.
AB  - PURPOSE: To determine if abnormalities in the protein C/protein S anticoagulant
      system exist in patients with phospholipid antibodies who had the primary
      clinical complaint of fetal wastage. PATIENTS AND METHODS: Eleven patients with
      fetal wastage and phospholipid antibodies were selected for study. Some patients
      also gave a history of previous thrombotic events related to oral contraceptives
      and/or pregnancy, but patients were not selected because of a history of clinical
      thrombosis. The levels of protein C (chromogenic assay), protein S (both free and
      bound) (Laurell rocket), and C4b-binding protein (Laurell rocket) were measured,
      and assays for the presence of antibodies against protein S or protein C were
      performed. RESULTS: Seven of the 11 patients were found to have low levels of
      free protein S. Total protein S and protein C levels were within the normal range
      in all patients. Antibodies to protein C and protein S were not found in any
      patient. These findings suggest that free protein S levels may be abnormally low
      in some patients with phospholipid antibodies. CONCLUSION: Free protein S levels
      are abnormally low in some patients with phospholipid antibodies, and this
      abnormality may be a factor contributing to the thrombotic diathesis associated
      with phospholipid antibodies.

PMID- 1385675
TI  - Education and engineering solutions for potential problems with laparoscopic
      monopolar electrosurgery.
AB  - The potential problems of monopolar electrosurgery relate to unrecognized energy
      transfer ("stray current") outside the view of the laparoscope. Mechanisms of
      stray current and unrecognized tissue injury include: (1) insulation breaks in
      electrodes; (2) capacitive coupling, or induced currents through the intact
      insulation of the active electrode to surrounding cannulas or other instruments;
      and (3) direct coupling (or unintended contact) between the active electrode and
      other metal instruments or cannulas within the abdomen. Capacitive coupling poses
      the greatest risk for injury when the outer conductor (trocar cannula or
      irrigation cannula) is electrically isolated from the abdominal wall by a plastic
      nonconductor. Capacitive coupling is increased by the coagulation mode (versus
      cut), open circuit (versus tissue contact with the electrode), 5-mm cannulas
      (versus 11 mm), and higher voltage generators. The safety of electrosurgery can
      be enhanced by surgical education regarding the biophysics of radio frequency
      electrical energy, technical choices in instruments using all-metal cannula
      systems, and engineering developments with a dynamically monitored system for
      insulation failure and capacitive coupling.

PMID- 1385676
TI  - A new technique for indirect inguinal hernia repair.
AB  - This report concerns a preliminary study of a new technique for indirect
      herniorraphy, which was used in 242 patients from December 1988 through March
      1991. Its main characteristics are the creation of a deep neo-inguinal ring in a
      more medial site, shortening of the inguinal canal by transposition of the
      superficial ring to the point where the inferior border of the internal oblique
      muscle is well represented, reinforcement of the inguinal canal by overlapping
      the external oblique aponeurosis in a double-breast fashion, and maintenance of
      the cremasteric muscle. Follow-up in our outpatient clinic was carried out at 1,
      6, 12, and 24 months in 71% of our patients. There were no recurrences, except
      for one crural pseudo-recurrence, no mortality, and no testicular atrophy.
      Thirteen percent of patients had subcutaneous serous collection; 1% had
      hematomas; 2% temporary testicular edema; and 0.4% wound infection.

PMID- 1385677
TI  - Positron emission tomography in the Rett syndrome: clinical, biochemical and
      pathological correlates.
AB  - A consistent constellation of clinical signs and symptoms define the Rett
      syndrome, the most prominent of which are disorders of movement and tone.
      Preliminary pathologic and neurochemical data indicate predominant involvement of
      the nigrostriatal dopaminergic pathways and the cholinergic system of the basal
      forebrain region. The age of onset differentiates the Rett syndrome from
      Alzheimer and Parkinson disease with similar lesions. PET scanning makes it
      possible to relate the chemistry of the brain to function by measuring the number
      and affinity of neuroreceptors, metabolism in specific brain regions, and provide
      important determinants of the underlying mechanisms in disease states.

PMID- 1385679
TI  - The involvement of NMDA receptors in acute and chronic effects of ethanol.
AB  - Recent evidence indicates involvement of excitatory amino acid receptors
      sensitive to N-methyl-d-aspartate (NMDA) in the action of ethanol (EtOH).
      Pronounced inhibition of NMDA receptor function is seen in vitro with
      concentrations of EtOH corresponding to those present during alcohol intoxication
      in humans. The present study was devoted to investigate the role of NMDA
      receptors in the action of EtOH in rats. Acute experiments showed antagonism by
      EtOH of convulsions induced by intracerebroventricular injection of NMDA. A
      similar effect was seen with a high dose of diazepam. Convulsions induced by an
      agonist of another excitatory amino acid receptor subtype, kainate, were also
      inhibited by EtOH. An uncompetitive antagonist of NMDA receptors, 5-methyl-10,11
      dihydro-5H-dibenzocyclohepten-5,10-imine maleate (MK-801), potentiated EtOH
      induced loss of righting, but attenuated the hypothermic action of EtOH.
      Moreover, MK-801 inhibited audiogenic convulsions in EtOH withdrawn rats. At the
      same time the effect of a proconvulsive dose of NMDA was not enhanced. Tolerance
      to the myorelaxant action of both EtOH and MK-801 upon repetitive administration
      was seen. Also some degree of cross-tolerance was observed. Moreover, MK-801
      failed to modify EtOH preference in rats. The present results support involvement
      of NMDA receptors in expression of some acute and subchronic actions of EtOH and
      in expression of EtOH withdrawal.

PMID- 1385678
TI  - Isradipine and other calcium channel antagonists attenuate ethanol consumption in
      ethanol-preferring rats.
AB  - The present work is concerned with studying of the ability of different calcium
      channel antagonists to modify voluntary ethanol ingestion by rats selectively
      bred for high ethanol preference. The compounds were given s.c. thrice daily for
      5 days at doses that did not produce locomotor impairment. While nifedipine,
      darodipine, and verapamil (each at the dose of 20 mg/kg thrice daily) produced a
      modest reduction in ethanol intake, isradipine (at the dose of 1 mg/kg three
      times a day) reduced ethanol intake by over 70%. For all compounds, the reduction
      in ethanol intake was compensated by a proportional increase in water consumption
      and the inhibitory effect persisted throughout the 5 days of treatment. The data
      indicate that calcium channel antagonists exhibit quite different potency in
      reducing ethanol preference, however this action is a general property of this
      class of compounds.

PMID- 1385680
TI  - Clinical evaluation of doxacurium chloride.
AB  - Doxacurium was administered to 50 adult patients for determination of potency (n
      = 10), onset and duration of clinical relaxation (n = 40). Cumulative dose
      response showed the ED95 to be 33.24 micrograms.kg-1 (95% confidence limits 27.4
      39.3). Doxacurium 33 micrograms.kg-1 was then administered to four groups of 10
      patients each who had anaesthesia maintained with either fentanyl-droperidol or
      halothane and nerve stimulation carried out with single-twitch stimulation at 0.1
      Hz or train-of-four stimulation at 2 Hz every 12 s. The onset and duration showed
      wide individual variation. The mean (SD) times to occurrence of maximal block
      were 8.5 (4.6), 6.1 (1.9), 6.7 (1.8) and 4.7 (1.3) min in the single twitch
      fentanyl, train-of-four--fentanyl, single twitch-halothane and train-of-four-
      halothane groups respectively, although it ranged from 3.4 to 13.1 min in
      individual patients. The mean (SD) durations of clinical relaxation (recovery of
      single twitch or first response in train-of-four to 25%) were 65 (22.8), 52
      (21.7), 70 (33.4) and 72 (21.0) min respectively with individual values ranging
      from 31 to 103 min. Although halothane administration increased the duration of
      clinical relaxation and train-of-four stimulation accelerated the onset of
      effect, the changes due to these were not significant. There were no adverse
      effects on heart rate or indirectly measured arterial pressure.

PMID- 1385681
TI  - Carbon dioxide pneumothorax occurring during laparoscopic cholecystectomy.
AB  - A previously fit patient underwent laparoscopic cholecystectomy. During the
      procedure arterial oxygen saturation fell and clinical examination revealed signs
      of a right pneumothorax confirmed by chest X ray. Aspiration of the pleural
      cavity and analysis of the gas removed showed it to be composed entirely of
      carbon dioxide. Possible mechanisms of entry of carbon dioxide into the pleural
      space are discussed.

PMID- 1385682
TI  - Double-blind study of intranasal ipratropium bromide in nonallergic perennial
      rhinitis.
AB  - We undertook this trial to determine whether ipratropium bromide nasal spray
      0.03% (IB) reduced the nasal hypersecretion associated with nonallergic perennial
      rhinitis (NAPR) without causing excessive dryness or irritation of the nasal
      mucosa. We compared two drug doses of IB (21 micrograms and 42 micrograms per
      nostril) to a placebo, administered as two sprays to each nostril twice daily.
      The study design consisted of a 1-week screening period without treatment, a 1
      week single-blind placebo period, a 4-week double-blind treatment comparison
      period, and a 1-week follow-up period without medication to evaluate nasal
      rebound. One hundred fifty-two patients were entered and 140 completed the trial.
      Both doses of IB reduced the severity and duration of rhinorrhea compared with
      placebo (P = .05 and .03, respectively). Treatment differences were noticeable
      during the first week of therapy, continued to widen during the second week, and
      then remained stable throughout the next 2 weeks. There was no evidence of nasal
      rebound observed during the week after treatment. The drug was well tolerated
      with side effects limited to infrequent nasal adverse events of nasal dryness,
      blood-tinged mucus, and epistaxis occurring in 2% to 6% of patients. We conclude
      that IB is a safe and effective therapy for control of rhinorrhea associated with
      NAPR.

PMID- 1385683
TI  - Inoculation of conventionally and specific-pathogen-free reared rabbits with
      Ostertagia ostertagi isolated from cattle.
AB  - Eleven trials were conducted to collect helminthologic and pathologic data from
      27 conventionally reared (CR) and 53 specific-pathogen-free (SPF) 6- to 13-week
      old male New Zealand White rabbits. These rabbits were given 50,000 to 100,000
      ensheathed third-stage infective Ostertagia ostertagi larvae (L3) orally. The L3
      had been isolated from the feces of cattle. Fecal egg counts were conducted and
      worm populations were determined after euthanasia 3 to 56 days after inoculation.
      At necropsy, nodules were observed in a confluent pattern in the mucosa of
      cardiac region of the stomach in all inoculated rabbits, except in CR rabbits
      inoculated at 6 weeks of age, which had no nodules or worm burdens 42 days after
      inoculation. Confluent areas were not observed in SPF rabbits euthanatized 5 days
      or less after inoculation; however, small, transparent nodules were evident in
      the mucosa of the cardiac region of the stomach. Fourth-stage larvae (L4) were
      obtained from the mucosal nodules after digestion of stomach of both types of
      rabbits. There were more L4 in SPF than CR rabbits. In addition, greater numbers
      of L4 were found in SPF rabbits euthanatized 14 days or less after inoculation.
      Petechial hemorrhages were in the fundic area of the stomach mucosa in SPF
      rabbits inoculated with 100,000 L3 and euthanatized 14 days later. Mature O
      ostertagi or worm eggs in feces were not found in inoculated CR or SPF rabbits.
      The pathologic changes had characteristics similar to those in cattle and goats
      infected with O ostertagi.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385684
TI  - Abdominal muscle use during breathing in patients with chronic airflow
      obstruction.
AB  - To assess the pattern of abdominal muscle contraction in stable patients with
      chronic obstructive pulmonary disease (COPD), we studied electromyograms of the
      rectus abdominis, external oblique, and transversus abdominis muscles in 40
      patients with variable degrees of chronic airflow obstruction (FEV1 between 17
      and 82% of predicted); 12 control subjects with normal pulmonary function tests
      were studied for comparison. The subjects were studied during resting breathing
      in the supine posture, and the electromyograms were recorded with concentric
      needle electrodes implanted with the aid of a high-resolution ultrasound. The
      rectus abdominis and external oblique were silent in virtually all patients. In
      contrast, 17 patients had invariable phasic expiratory activity in the
      transversus abdominis, and 11 additional patients had intermittent transversus
      expiratory activity. Expiratory contraction of the transversus was related to the
      degree of airflow obstruction (p less than 0.005), and when present, it persisted
      in the seated posture. We conclude that (1) when breathing at rest, many stable
      patients with severe chronic airflow obstruction contract the abdominal muscles
      during expiration, and (2) this expiratory contraction is usually confined to the
      transversus muscle. These observations also indicate that the physiology of
      dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP) in
      such patients should be reevaluated.

PMID- 1385685
TI  - Oxytocin facilitation of maternal behavior in sheep.

PMID- 1385686
TI  - Potential role of immunomodulators for treatment of phlebovirus infections of
      animals.
AB  - Rift Valley fever (RVFV) is a major phlebovirus-induced epizootic disease of
      domestic animals (primarily cattle and sheep) in Africa. No therapies for the
      disease are known. A related phlebovirus, Punta Toro virus (PTV), has been
      adapted to induce an RVFV-like disease in C57BL/6 mice. This PTV infection has
      been used as a model for RVFV because it is reasonably safe and does not require
      high-level biologic containment. The infection model has been used to study the
      potential role of immunomodulating substances as therapies. A spectrum of
      immunomodulators has been studied; those immunomodulators most capable of
      preventing death and other disease manifestations are ampligen, bropirimine, poly
      (ICLC), AM-3, P-136, and 7-thia-8-oxoguanosine. An immunologic parameter common
      to all these substances has been their ability to induce interferon. Timing
      studies have indicated that these active substances may be administered
      therapeutically as well as prophylactically to inhibit markedly the progress of
      the disease. Further work is needed in the development of these materials for use
      in treating viral infections in domestic animals. As a next step, studies need to
      be run to compare the immunologic profiles induced by each substance in domestic
      animals and in mice.

PMID- 1385687
TI  - Evaluation of Lp(a) as a risk factor of coronary artery disease in the Korean
      population.

PMID- 1385688
TI  - [Co-operative clinical evaluation of 5'-DFUR tablets for breast cancer at 31
      institutions].
AB  - A phase II study of 5'-deoxy-5-fluorouridine (5'-DFUR) tablets for breast cancer
      was done at 31 institutions in Japan. Forty-five patients were registered and 44
      of them were eligible for the study. Of the 40 patients whose results could be
      evaluated, 11 (28%) responded (four complete responses and seven partial
      responses). Side effects, such as diarrhea, anorexia, leukocytopenia, and liver
      dysfunction were observed in 24 of the 44 patients. The side effects were mild
      and transient. 5'-DFUR is a promising drug for breast cancer treatment, and its
      tablet form makes chemotherapy easier for the patient.

PMID- 1385690
TI  - [A case report; 5'-DFUR reduced gastric cancer with multiple liver metastasis].
AB  - We describe a case of gastric cancer with multiple liver metastasis that clearly
      decreased in size after administration of 5'-DFUR. The patient (a 63-year-old
      male) was inoperable because of multiple liver metastasis. 5'-DFUR 600 mg/day
      reduced the size of the multiple liver tumors (reduction rate 90%, partial
      response for four months), but the gastric tumor was unaltered. A rapid decrease
      in alkali-phosphatase indicated reduction of the liver tumors only one week after
      the initiation of 5'-DFUR.

PMID- 1385689
TI  - [A case of advanced breast cancer responding to low-dose 5'-DFUR].
AB  - A 69-year-old female patient with locally advanced breast cancer with multiple
      bone metastases (T4cN2-M1) was treated with 5'-DFUR after failure of tamoxifen
      treatment. The 5'-DFUR dose was limited to 600 mg per day, half the usual dose,
      because of its gastroenterological side effects. The primary tumor and metastatic
      axillary lymph nodes regressed three months after the start of treatment, and the
      complete remission of lesions was obtained in 16 months. Reduction of bone
      metastasis was confirmed by the disappearance of osteolytic lesion in the skull
      roentgenogram and the decrease of abnormal accumulation on the bone scintigram.
      Serum levels of CEA and ST-439 markedly reduced during the treatment as the
      disease regressed.

PMID- 1385691
TI  - Recalcitrant onychomycosis of the toenails successfully treated with fluconazole.

PMID- 1385692
TI  - Two divergent findings in TEN.

PMID- 1385694
TI  - Drug treatment of canine acral lick. An animal model of obsessive-compulsive
      disorder.
AB  - Canine acral lick dermatitis is a naturally occurring disorder in which excessive
      licking of paws or flank can produce ulcers and infection that require medical
      treatment. Forty-two dogs with severe chronic canine acral lick dermatitis were
      treated in three double-blind crossover comparisons of clomipramine
      hydrochloride/desipramine hydrochloride, fluoxetine hydrochloride/fenfluramine
      hydrochloride, and sertraline hydrochloride/placebo. The serotonin uptake
      blocking drugs were clinically effective, while the other drugs were not. Based
      on phenomenology and pharmacological response, we propose canine acral lick
      dermatitis as an animal model of obsessive-compulsive disorder.

PMID- 1385695
TI  - Microleakage of glass ionomer/composite resin restorations: a laboratory study.
      Part 2. The influence of bonding systems.
AB  - Acid-etching and bonding of composite resin to bevelled enamel margins has been
      reported to produce a reliable seal. However, achieving a seal with dentine and
      cementum margins is more difficult. Four different dentine bonding systems were
      used in combination with Silux composite resin to restore cervical cavities in
      vitro. None of the bonding systems used completely sealed either the occlusal or
      gingival margins. Of the four systems, GLUMA provided the best seal at both the
      occlusal and gingival margins.

PMID- 1385693
TI  - The Scottish low birthweight study: I. Survival, growth, neuromotor and sensory
      impairment.
AB  - Of all 908 livebirths weighing less than 1750 g at birth who were born in
      Scotland in 1984, 896 (99%) were enrolled in a prospective study to document
      survival and determine the prevalence of neuromotor and sensory impairments and
      disability. At the age of 4.5 years, 636 (71%) had survived and 611 (96%) were
      assessed. Overall 16% were disabled; 47 had cerebral palsy (52.5/1000
      livebirths), seven were blind (7.8/1000 livebirths), and 11 were deaf and using
      aids (12.3/1000 livebirths). Among those not overtly disabled, the prevalence of
      poor neuromotor competence was high and related to birth weight. All growth
      measures had mean values below the standard population mean indicating a downward
      shift in the distribution which was related to birth weight. In addition the
      height distribution was negatively skewed.

PMID- 1385696
TI  - A laboratory investigation of a composite resin/dentine bonding agent mixture
      used as a root canal sealer.
AB  - The objective of this project was to determine the effectiveness of a dentine
      bonding agent, in conjunction with a composite resin, to act as an endodontic
      sealing material. The effectiveness was compared with that provided by a
      conventional sealer (AH26) by measuring dye penetration into the root canal. Two
      obturation techniques were used with each sealer; the single gutta-percha point
      technique, and lateral condensation with multiple gutta-percha points. Lateral
      condensation with the conventional sealer was found to be the superior procedure,
      by producing the least amount of linear leakage (coronally from the apex) on
      average. However, the single point technique with the composite resin/dentine
      bonding agent sealer provided the greatest number of 'no leakage' samples.
      Scanning electron microscope investigation of obturated roots revealed the
      presence of resin tags in dentine tubules only in those samples where the
      composite resin/dentine bonding agent sealer was used. The short working time
      provided by the composite resin/dentine bonding agent sealer prevented successful
      obturation using lateral condensation. The provision of an extended working time
      composition for this sealer may produce more favourable results in obturation
      with lateral condensation.

PMID- 1385697
TI  - Myocardial infarction (Part 3).

PMID- 1385698
TI  - Evaluation of a Mycoplasma gallisepticum strain exhibiting reduced virulence for
      prevention and control of poultry mycoplasmosis.
AB  - Two experiments were conducted to evaluate the virulence and vaccination efficacy
      of a Mycoplasma gallisepticum (MG) isolate designated MG Intervet 6/85. Virulence
      of the strain was determined by evaluation of airsacculitis scores following
      aerosol exposure to the isolate before and after 10 sequential passes in either
      commercial broiler chickens or commercial turkeys. Two-week-old specific-pathogen
      free chickens were vaccinated by aerosol exposure. The birds were challenged with
      the R' strain of MG at either 4 or 8 weeks post-vaccination. Efficacy was
      evaluated by airsacculitis scores determined 21 days after challenge. Ten
      repetitive back-passes of the isolate in chickens and turkeys did not
      substantially increase the virulence. Virulence for both chickens and turkeys was
      minimal, while protection elicited by aerosol vaccination in young chickens
      against virulent R' strain was significant (P less than or equal to 0.05)
      compared with unvaccinated controls.

PMID- 1385699
TI  - Serological response of chickens to infection with Salmonella gallinarum-S.
      pullorum detected by enzyme-linked immunosorbent assay.
AB  - The serological response to Salmonella pullorum and S. gallinarum infection in
      chickens was studied with an indirect enzyme-linked immunosorbent assay (ELISA).
      In broiler chickens, a more virulent strain of S. pullorum produced a
      significantly lower serum IgG titer than did a less virulent strain. In laying
      hens, the serum and egg-yolk IgG titers were very similar. In chickens infected
      with S. gallinarum, high IgG titers persisted for 30 weeks. In chickens
      reinfected with this strain, each reinfection was followed by transitory
      increases in IgG lasting no longer than 2 weeks. Serum samples from Brazil taken
      from a laying flock with evidence of fowl typhoid showed much higher antibody
      levels than did those from three uninfected flocks. Using lipopolysaccharide as
      the detecting antigen, infections caused by these salmonellae could be
      differentiated from those caused by other groups. Incorporation of the
      appropriate flagella antigen in the ELISA allowed differentiation between
      infections caused by S. pullorum and S. enteritidis.

PMID- 1385700
TI  - Avian paramyxovirus type 1 infections in racing pigeons in California. I.
      Clinical signs, pathology, and serology.
AB  - An outbreak of diarrhea and neurological disease in California racing pigeons
      caused by avian paramyxovirus type 1 (PMV-1) is documented. Predominant clinical
      signs were polydipsia, ataxia, poor balance, torticollis, head tremors, inability
      to fly, and diarrhea that was unresponsive to therapy. Gross pathologic findings
      were often unremarkable or non-specific. The predominant histologic lesions were
      interstitial nephritis, chronic tubular necrosis, lymphoplasmacytic infiltration
      within the kidney, liver, and pancreas, and focal non-suppurative encephalitis.
      Pigeons from 20 submissions demonstrated characteristic clinical signs of PMV-1
      infection. Pigeons from 17 submissions exhibited typical histopathology.
      Serologic evidence of PMV-1 infection was present in pigeons from 13 submissions,
      and PMV-1 was isolated from pigeons received in six submissions. None of these
      pigeons had been vaccinated against PMV-1.

PMID- 1385701
TI  - Severe problem behaviors related to social interaction. 1: Attention seeking and
      social avoidance.
AB  - Studies concerning the functional analysis of severe problem behaviors have
      suggested that it is important to identify the different categories of stimuli
      that control problem behavior because each has unique treatment implications. The
      present study explored the differential effects of adult attention on the severe
      problem behaviors of two groups of children with developmental disabilities. A
      third group of nonproblem children was examined for comparison purposes. Children
      participated in three experimental conditions in which the level of adult
      attention was manipulated: noncontingent high attention, noncontingent low
      attention, and contingent attention. Results validated the existence of two
      groups of children who differed as to their social orientation: (a) One group of
      children commonly initiated social interactions and was most likely to exhibit
      problem behaviors under conditions of low adult attention, and (b) the other
      group of children rarely initiated social interactions and exhibited frequent
      problem behaviors under conditions of high adult attention. Implications of these
      data for escape and attention theories of child problem behavior are discussed,
      as are the applied implications for reinforcer assessment and teaching
      strategies.

PMID- 1385702
TI  - Severe problem behaviors related to social interaction. 2: A systems analysis.
AB  - The effects of problem behavior displayed by two groups of children with
      developmental disabilities was investigated. One group of children exhibited
      problem behavior under conditions of low adult attention and was referred to as
      the attention-seeking or AS behavior profile group. A second group of children
      exhibited problem behavior under conditions of high adult attention and was
      referred to as the socially avoidant or SA behavior profile group. A third group
      of nonproblem children (NP) was examined for comparison purposes. Pairs of
      children were placed in a teaching situation, and the effects of child problem
      behavior upon adult instructional behavior were measured. Results indicated that
      child behavior affected adult behavior and that different child behavior profiles
      affected adults differentially. Adults responded to the problem behaviors of the
      AS behavior profile group by increasing attention, providing higher levels of
      physical contact, and presenting academic tasks that required continuous adult
      child interaction. Conversely, the same adults responded to the problem behaviors
      of the SA behavior profile group by reducing attention, providing lower levels of
      physical contact, and presenting academic tasks that required little adult-child
      interaction. The data indicated that these child effects were powerful,
      immediate, and durable. Theoretical implications concerning reciprocal social
      influence and the operant theory of child problem behavior are discussed. Applied
      implications concerning treatment selection and maintenance are also explored.

PMID- 1385704
TI  - Metabolic fate of nicotinamide in LEC rats.
AB  - Metabolic fates of nicotinamide in Wistar and LEC rats were compared. In Wistar
      rats (normal rats) nicotinamide was generally catabolized to N1-methyl-4-pyridone
      3-carboxamide (4-Py) through N1-methylnicotinamide (MNA). But in LEC rats
      nicotinamide catabolism mainly stopped at MNA. Therefore, the excretion ratio of
      (N1-methyl-2-pyridone-5-carboxamide + 4-Py)/MNA, which is an index of amino acid
      adequacy, was much lower in the LEC rats than in the Wistar rats. This phenomenon
      was attributed to the fact that the 4-Py-forming MNA oxidase activity was much
      lower in the LEC rats than in the Wistar rats. The NAD contents in liver and
      blood were also lower in LEC rats than in Wistar rats. These results suggest that
      the ability to synthesize proteins such as 4-Py-forming MNA oxidase and
      dehydrogenases may be impaired in LEC rats.

PMID- 1385703
TI  - Hepatocyte growth factor rapidly induces the tyrosine phosphorylation of 41-kDa
      and 43-kDa proteins in mouse keratinocytes.
AB  - We have examined the hepatocyte growth factor (HGF)-mediated changes in protein
      tyrosine phosphorylation in mouse keratinocytes (PAM-212) and canine kidney
      epithelial cells (MDCK). In PAM-212 cells HGF and epidermal growth factor, both
      of which stimulated the DNA synthesis, rapidly induced the tyrosine
      phosphorylation of two 41-kDa and two 43-kDa proteins: increased tyrosine
      phosphorylation of those proteins has been commonly observed when quiescent
      fibroblasts are stimulated with a variety of mitogenic agents. In contrast, HGF
      did not stimulate the DNA synthesis but induced cell dissociation in MDCK cells;
      under this condition, increased tyrosine phosphorylation of the 41-kDa and 43-kDa
      protein was not observed. A possible role of the increased tyrosine
      phosphorylation of 41-kDa and 43-kDa protein in the signaling pathway of HGF is
      discussed.

PMID- 1385705
TI  - Inhibition of gastric mucosal laminin receptor by Helicobacter pylori
      lipopolysaccharide: effect of ebrotidine.
AB  - The effect of lipopolysaccharide from H. pylori, a bacteria implicated in the
      etiology of gastric disease, on the gastric mucosal laminin-receptor interaction
      was investigated. The receptor protein, prepared from rat gastric epithelial cell
      membrane by affinity chromatography on laminin-coupled Sepharose, was
      radioiodinated, and incorporated into liposomes which exhibited specific affinity
      towards laminin-coated surface. The binding was inhibited by H. pylori
      lipopolysaccharide, which caused a maximum inhibition of 96% at 50 micrograms/ml.
      The inhibitory effect of the lipopolysaccharide was prevented by an antiulcer
      agent, ebrotidine that evoked essentially complete restoration in binding at 6-8
      micrograms/ml. The results demonstrate that H. pylori through its
      lipopolysaccharide interferes with gastric epithelial cell-laminin binding, and
      that this disruptive effect could be successfully countered by ebrotidine.

PMID- 1385706
TI  - Atrial natriuretic factor concentrations during pregnancy and in the postpartum
      period.
AB  - Atrial natriuretic factor (ANF) is a hormone that regulates fluid and electrolyte
      homeostasis. Increased intra-atrial pressure or atrial distention, which might
      occur secondary to intravascular volume expansion, stimulate the secretion of ANF
      by human atrial myocytes. During normal human pregnancy, there is a progressive
      increase in total intravascular fluid volume. Thus, we asked the following
      question: Does this physiologic adaptation to pregnancy result in an increase in
      ANF concentrations? Concentrations of alpha-human ANF (alpha-hANF) were measured
      by a specific radioimmunoassay in venous blood samples obtained longitudinally in
      the first, second, and third trimesters of pregnancy, during the intrapartum
      period, in the early postpartum period, and 6 to 8 weeks postpartum from 11
      normal women who had no antepartum, intrapartum, or postpartum complications.
      Maternal circulating alpha-hANF levels were not different from those seen in the
      nonpregnant state. However, higher alpha-hANF concentrations were noted in the
      early postpartum period. Although the hypervolemia of normal pregnancy is not
      associated with higher alpha-hANF concentrations, other possibilities (such as
      increased ANF clearance, dilutional effects) need to be investigated. Finally,
      the etiology for the transient increase in alpha-hANF levels in the early
      postpartum period remains to be elucidated.

PMID- 1385707
TI  - Biological properties of interleukin 10.
AB  - An enormous amount of information on interleukin 10 (IL-10) has been gathered
      since its original description as cytokine synthesis inhibition factor (CSIF)
      several years ago. In this short article, Maureen Howard and Anne O'Garra
      summarize what is currently known of the biological properties of IL-10 and
      speculate on its clinical potential.

PMID- 1385708
TI  - Regulation of alpha 1-antitrypsin synthesis by granulocyte macrophage colony
      stimulating factor in the U937 promonocytic cell line.
AB  - Undifferentiated U937 cells possess low numbers (approximately 1,100 per cell) of
      receptors for granulocyte macrophage colony-stimulating factor (GMCSF). The
      receptors present are of at least two types with different affinities. A small
      number (less than 200 per cell) are of higher affinity (approximate Kd 97pM), and
      a larger number (approximately 900 per cell) are of lower affinity (approximate
      Kd 680pM). Following differentiation with the phorbol ester 12-O
      tetradecanoylphorbol 13-acetate (PMA), the differentiated cells express a reduced
      number of receptors (approximately 680 per cell). These receptors are present as
      a single class with an approximate affinity of 230pM (Kd). The undifferentiated
      cells were responsive to GMCSF and this cytokine caused a seven-fold increase in
      accumulation of alpha 1-antitrypsin (alpha 1AT) compared to the control cells.
      This was accompanied by a similar increase in alpha 1ATmRNA, which suggests that
      the rate of alpha 1AT accumulation was regulated at the transcriptional level.
      After differentiation with PMA, alpha 1AT accumulation was not influenced by
      GMCSF, although the cells continued to bind the cytokine. These results imply
      that U937 cells do respond to GMCSF and this event involves binding of the ligand
      to a small number of specific cell surface receptors only present in the
      undifferentiated cells. Furthermore the response of these cells (in terms of
      alpha 1AT production) is associated with the type of GMCSF receptors expressed.

PMID- 1385709
TI  - WY 18,251 (Tilomisole), an analog of levamisole: tolerability, and immune
      modulating effects in cancer patients.
AB  - Wy 18,251 (Tilomisole; Wyeth Laboratories, Philadelphia, PA, USA) is a
      benzimidazole that is structurally similar to the antihelminth levamisole that
      has recently been approved for the adjuvant treatment of colon cancer. In
      preclinical models, Tilomisole caused less agranulocytosis than levamisole, but
      retained immunomodulating capabilities. We examined the effects of Tilomisole
      administered to cancer patients in four different dose schedules: 60 mg/m2 orally
      (p.o.) weekly, and 60, 300, or 960 mg/m2 p.o. daily for 1 month. All patients
      were immunosuppressed when treatment was initiated as defined by standardized
      assays of phytohemagglutinin, concanavalin A, pokeweed mitogen, and mixed
      lymphocyte responses. Tilomisole was well tolerated with no significant side
      effects in 25 patients. There were no antitumor responses noted in this setting
      of metastatic cancer. There was no improvement in concanavalin A or pokeweed
      mitogen assays at any dose or schedule, but there was sustained improvement in
      mixed lymphocyte reaction and phytohemagglutinin assays at the 60 mg/m2 daily
      dose. This drug may have favorable biological response modifying effects in vivo
      and be a suitable alternative to levamisole in cancer treatment, especially if
      agranulocytosis is a significant problem associated with widespread use of
      levamisole.

PMID- 1385710
TI  - Production of hybrid bispecific antibody recognizing human colorectal carcinoma
      and CD3 antigen.
AB  - The present study reports on the use of gene transfer by vector DNA in the
      generation of hybrid hybridoma, the quadroma secreting the hybrid bispecific
      antibody. A quadroma B72.3neo/OKT3gpt was simply derived from the fusion of two
      hybridoma cell lines, B72.3 and OKT3, tagged with vector DNA mpSV2neo and
      mpSV2gpt, respectively, and selected in the media containing both G418 and
      mycophenolic acid. The hybrid bispecific antibody B72.3/OKT3 was purified from
      the quadroma ascites by the use of hydroxylapatite column on high-pressure liquid
      chromatography. This bispecific antibody contained one binding site for the TAG72
      antigen on OVCAR3 tumor cells and the other binding site for the CD3 molecule on
      human T cells. It was able to target human T lymphocytes to significantly lyse
      the human ovarian cancer cells and may therefore be useful in immunotherapy of
      cancer.

PMID- 1385712
TI  - Functional outcome in children with traumatic brain injury. Agreement between
      clinical judgment and the functional independence measure.
AB  - As improvements in the delivery of trauma care have increased survival from
      injury, it has become essential to assess the resulting morbidity to plan for
      medical and psychosocial services, particularly for children whose needs may be
      wide and long term. This paper focuses on the assessment of disability of 598
      children, age 8 to 19 yr, hospitalized for traumatic brain injury with or without
      injury to other body regions, exclusive of spinal cord injury. The disability was
      measured at discharge from acute care in nine areas of functional activities and
      a recovery time assigned by a clinician. For the study, children were divided
      into three groups: those whose recovery was expected in less than 7 months (Group
      A: n = 463), in 7 to 24 months (Group B: n = 66) and in greater than 2 yr (Group
      C: n = 69). The clinician's expectation of recovery time significantly (P less
      than 0.01) reflected the injury severity as measured by the Glasgow Coma Scale
      and the Injury Severity Score. By the Glasgow Coma Scale, 16.4% were comatose on
      admission in Group A, 51.5% in Group B and 58% in Group C. The Injury Severity
      Score was significantly different with 25.5% severely injured in Group A, 68.2%
      in Group B and 84% in Group C. At discharge, 15% in Group A had four or more
      areas of impairments, 61% in Group B and 84% in Group C. The Functional
      Independence Measure confirmed the clinician's assessment of compromise with
      significantly (P less than 0.01) different average values of 110, 80 and 58 for
      Groups A, B and C, respectively.

PMID- 1385711
TI  - Providing care to persons with physical disability. Effect on family caregivers.
AB  - Studies on caregiving often assume that outcomes will be problematic and assess
      negative factors, such as burden or stress. Results may be biased by detailing
      only the problems encountered. The current study assessed positive, neutral and
      negative aspects of caregiving and evaluated the impact of caregiving using
      criteria based on an accepted model of family functioning. Of 942 consecutive
      hospital admissions, 217 subjects required assistance in personal care and
      returned home with a primary caregiver. Caregivers reported moderately more
      anxious, depressive and somatic symptoms than expected from standardized tests,
      but these findings were not clinically or statistically significant. Family
      functioning was related to the duration of the caregiving experience. Family
      relations seemed to be a source of strength for caregivers, regardless of
      disability type. Further research is needed to determine if family functioning
      can be used to buffer against unfavorable aspects of caregiving or to enhance
      positive aspects of the situation.

PMID- 1385713
TI  - Rehabilitation in adults with human immunodeficiency virus-related diseases.
AB  - The acquired immunodeficiency syndrome is a fatal disorder of cell-mediated
      immunity caused by the human immunodeficiency virus (HIV). As many as one million
      Americans infected with HIV can expect improved survival with more advanced
      treatment approaches. Complications of HIV infection occur in the brain, spinal
      cord, muscle, nerve, joints and other organ systems, which lead to extensive
      impairments. As survival increases, rehabilitation professionals can anticipate a
      greater number of referrals for the assessment and management of physical
      disability in persons with HIV infection. This article reviews HIV-related
      disease, impairment, disability and handicap pertinent to rehabilitation
      medicine. An agenda for future research is also proposed. Current knowledge and
      models or rehabilitation care can be applied to HIV-related physical disability
      in an effort to improve overall quality of life.

PMID- 1385714
TI  - Endothelin peptides: biological activities, cellular signalling and clinical
      significance.
AB  - Endothelins (ET-1, ET-2 and ET-3) are a family of 21 amino acid peptides produced
      by endothelial cells. They are thought to regulate the local vasomotor tone with
      endothelium-derived relaxing factors. ETs are the most potent vasoconstrictor
      substances yet identified and veins and renal vasculature are the most sensitive
      targets. They reduce cardiac output and have positive inotropic and chronotropic
      effects. ETs increase the secretion of atrial natriuretic peptide (ANP),
      aldosterone and catecholamines but reduce renal blood flow and glomerular
      filtration and they also have mitogenic properties. ETs bind to receptors (ETA
      and ETB), activate phospholipase C, modulate intracellular Ca2+ concentration and
      open Ca2+ channels. Vasoactive agents (adrenaline, angiotensin, vasopressin,
      thrombin, endotoxins) and hypoxia stimulate the release of ET and also ET gene
      expression. Raised concentrations of plasma ET have been found to occur in
      several clinical conditions such as hypertension, myocardial infarction,
      cardiogenic shock, pregnancy induced hypertension, arteriosclerosis, Raynaud's
      disease, subarachnoid haemorrhage, uraemia, ulcerative colitis, Crohn's disease
      and surgical operations suggesting that ETs have a role in several
      patophysiological processes.

PMID- 1385715
TI  - Post-mortem observations of a recent radiofrequency catheter ablation site.
AB  - The acute and chronic gross and microscopic morphologic changes present in
      myocardium after radiofrequency catheter ablation have been previously described
      in animal experiments. Acute changes have also been described in four cadaveric
      human specimens. We describe post-mortem observations of a recent radiofrequency
      catheter ablation site in a patient who underwent successful ablation for
      refractory ventricular tachycardia. Our gross and microscopic observations are
      similar to those previously described in animal experiments and confirm that the
      animal experimental results can be extrapolated to human hearts. As the use of
      radiofrequency becomes more prevalent as an alternative treatment for refractory
      cardiac tachycardias, pathologists will be called upon to identify post-mortem
      the lesions described. These lesions can be specifically identified, which can
      serve as a useful verification for this procedure.

PMID- 1385716
TI  - The clinicopathological implication of myocytes with contraction bands in autopsy
      hearts. Quantitative analysis of myocytes with contraction bands in autopsy
      hearts.
AB  - To define the normal extent of myocytes with contraction bands, 51 adult
      autopsied hearts including 30 normal and 21 common hypertrophic hearts were
      studied. Based on the histologic features, contraction bands were divided into
      mild and severe types. They were found in 48 and 32 of the total 51 cases,
      respectively. However, in five hearts, myocytes with contraction bands were more
      diffused or localized in one part of the ventricular wall. There were no special
      different treatments before death among the five cases or others. They seemed
      however to correlate with sudden death or acute cerebral damages. Therefore,
      reperfusion injury and metabolic cell injuries were considered. If these 5 cases
      were excluded, the normal extend of myocytes with contraction bands was
      considered as less than a 1.7% area in the mild type and a 0.5% area in the
      severe type found in the ventricular wall. These mild and severe contraction
      bands were considered related to autolysis or events occurring before death.

PMID- 1385717
TI  - Desmoid tumours treated with triphenylethylenes.
AB  - Desmoids are uncommon mesenchymal tumours that occur at single or multiple
      anatomical sites, occasionally in association with polyposis coli. This paper
      describes the use of the triphenylethylene tamoxifen, and a new chlorinated
      analogue, toremifene, in 20 patients with progressive desmoid disease. Clinical
      responses ranging from stabilisation of disease to complete resolution were
      observed in 65% of cases. The antitumour activity of this group of drugs has been
      attributed to their anti-oestrogenic behaviour. However, desmoids provide a
      clinical model of a purely mesenchymal tumour which appears to respond despite
      having generally low levels of hormone receptor. This emphasises the significance
      of stroma within breast (and other) tumours, in particular how the stroma may
      regulate the response to these drugs regardless of receptor status.

PMID- 1385718
TI  - Epidemiology of vertebral osteoporosis.
AB  - Whereas the extent, morbidity and costs of hip and Colles' fracture are well
      recognised from epidemiological studies, those arising from vertebral fracture
      are less secure. Reasons relate to the uncertain definition of vertebral fracture
      and its variable clinical expression, and hence its incidence is not known.
      Utilising radiological criteria 50% or more of vertebral fractures may be
      asymptomatic. In the remainder morbidity is significant, particularly in the
      presence of multiple vertebral fractures. Although the true incidence of
      vertebral fracture is unknown there is evidence that it increases exponentially
      with age in much the same way as for hip fracture. Between the ages of 60 and 90
      years the apparent incidence rises approximately 20-fold in women compared to a
      50-fold increase in risk of hip fracture. The incidence of vertebral osteoporosis
      is two-fold lower in men than in women at all ages, comparable to the pattern
      observed with other osteoporotic fractures. However, there is a relatively high
      incidence of vertebral fracture in men during middle adult-life (probably due to
      trauma), so that the prevalence of vertebral fracture in the male community is
      not two-fold less than in women.

PMID- 1385719
TI  - Quality of life in clinical trials of adjuvant therapies. International Breast
      Cancer Study Group (formerly Ludwig Group).
AB  - Clinical trials of adjuvant therapies usually measure the effectiveness of
      treatments by comparing disease-free survival or overall survival. These take
      into consideration only indirectly the quality of life experienced by the
      patients. We present some approaches that were developed to assess the impact of
      adjuvant therapy on the quality of life of breast cancer patients, as well as new
      methods created to compare treatments based on time spent without symptoms and
      toxicity (TWiST). The integration of these two methods (measuring quality and
      comparing duration of time) will provide a new tool for evaluating benefits from
      treatments given in the adjuvant setting.

PMID- 1385720
TI  - Reporting and interpreting adjuvant therapy clinical trials. International Breast
      Cancer Study Group (formerly Ludwig Group).
AB  - Identifying effective adjuvant treatments for patients with node-negative breast
      cancer is made difficult by the heterogeneity of the disease, the relatively low
      event rate and long follow-up time required, and the small magnitude of effects
      of current therapies. Several aspects of clinical trials that influence the
      appropriate reporting and interpretation of statistical results are discussed. We
      point out that the P value is a measure of the statistical uncertainty of an
      observed outcome and depends on the number of events available for analysis; it
      is not a measure of the magnitude of a treatment effect. We recommend that the
      relative reduction in the risk of an event and its 95% confidence interval be
      presented as an estimate of the treatment effect size, and that absolute
      improvements be used to judge whether treatment benefits outweigh the costs for
      the patient population. We suggest that subgroup analyses are important to define
      treatment effects within groups with different prognoses, and should be used with
      the understanding that multiple comparisons increase the chance of a false
      positive result. Subgroup analysis should rely on the estimates of relative
      treatment effect and should avoid the use of the P value to declare incorrectly
      that "treatment is effective for one subgroup but not for another." We present
      the meta-analysis (overview) as a powerful method to demonstrate the statistical
      significance of a modest treatment effect by increasing the number of events
      available for analysis. The interpretation of overviews should consider the
      potential for treatment interactions and the validity of indirect comparisons
      that are not protected by a randomized design.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385721
TI  - Advances in pediatric interventional radiology.
AB  - The past year has seen important papers on the risk of acquired immunodeficiency
      syndrome in the invasive radiology laboratory with emphasis on awareness and
      prevention. Interventional catheterization techniques in congenital heart disease
      are reviewed. Valvoplasty of pulmonic stenosis has the greatest success and least
      complication rate. The majority of complications appear to be at the vascular
      access site and are more common in neonates and in procedures that are ultimately
      unsuccessful. Intrauterine valvoplasty of the aortic valve is reviewed as is
      angioplasty for a recurrent coarctation of the aorta. Closure of a persistent
      ductus arteriosus with a percutaneously introduced prosthesis and occlusion of
      congenital coronary artery arteriovenous fistulae with a variety of embolic
      agents is reviewed. The use of balloon-expandable stents in congenital heart
      disease is discussed. Traumatic rupture of the aorta, aortic and great vessel
      involvement in Takayasu's disease, and mucopolysaccharidosis are reviewed along
      with imaging of congenital anomalies of the aortic arch. The diagnosis of
      vascular complications of renal transplants is summarized.

PMID- 1385722
TI  - Peripheral tolerance through clonal deletion of mature CD4-CD8+ T cells.
AB  - Transgenic mice bearing the alpha beta transgenes encoding a defined T cell
      receptor specific for the male (H-Y) antigen presented by the H-2Db class I MHC
      molecule were used to study mechanisms of peripheral tolerance. Female transgenic
      mice produce large numbers of functionally homogeneous CD8+ male antigen-reactive
      T cells in the thymus that subsequently accumulate in the peripheral lymphoid
      organs. We have used three experimental approaches to show that male reactive
      CD8+ T cells can be eliminated from peripheral lymphoid organs after exposure to
      male antigen. (i) In female transgenic mice that were neonatally tolerized with
      male spleen cells, male reactive CD8+ T cells continued to be produced in large
      numbers in the thymus but were virtually absent in the lymph nodes. (ii)
      Injection of thymocytes from female transgenic mice into female mice neonatally
      tolerized with the male antigen, or into normal male mice, led to the specific
      elimination of male-reactive CD8+ T cells in the lymph nodes. (iii) Four days
      after male lymphoid cells were injected intravenously into female transgenic
      mice, male antigen-reactive CD8+ T cells recovered from the lymph nodes of
      recipient mice were highly apoptotic when compared to CD4+ (non-male reactive) T
      cells. These data indicate that tolerance to extrathymic antigen can be achieved
      through elimination of mature T cells in the peripheral lymphoid organs.

PMID- 1385723
TI  - Labeling the (Ca(2+)-Mg2+)-ATPase of sarcoplasmic reticulum with 4-(bromomethyl)
      6,7-dimethoxycoumarin: detection of conformational changes.
AB  - The (Ca(2+)-Mg2+)-ATPase of sarcoplasmic reticulum was labeled with 4
      (bromomethyl)-6,7-dimethoxycoumarin. It was shown that a single cysteine residue
      (Cys-344) was labeled on the ATPase, with a 25% reduction in steady-state ATPase
      activity and no reduction in the steady-state rate of hydrolysis of p-nitrophenyl
      phosphate. The fluorescence intensity of the labeled ATPase was sensitive to pH,
      consistent with an effect of protonation of a residue of pK 6.8. Fluorescence
      changes were observed on binding Mg2+, consistent with binding to a single site
      of Kd 4 mM. Comparable changes in fluorescence intensity were observed on binding
      ADP in the presence of Ca2+. Binding of AMP-PCP produced larger fluorescence
      changes, comparable to those observed on phosphorylation with ATP or acetyl
      phosphate. Phosphorylation with P(i) also resulted in fluorescence changes; the
      effect of pH on the fluorescence changes was greater than that on the level of
      phosphorylation measured directly using [32P]P(i). It is suggested that different
      conformational states of the phosphorylated ATPase are obtained at steady state
      in the presence of Ca2+ and ATP and at equilibrium in the presence of P(i) and
      absence of Ca2+.

PMID- 1385725
TI  - 1H, 13C, and 15N NMR assignments and global folding pattern of the RNA-binding
      domain of the human hnRNP C proteins.
AB  - The hnRNP C1 and C2 proteins are abundant nuclear proteins that bind avidly to
      heterogeneous nuclear RNAs (hnRNAs) and appear to be involved with pre-mRNA
      processing. The RNA-binding activity of the hnRNP C proteins is contained in the
      amino-terminal 94 amino acid RNA-binding domain (RBD) that is identical for these
      two proteins. We have obtained the 1H, 13C, and 15N NMR assignments for the RBD
      of the human hnRNP C proteins. The assignment process was facilitated by
      extensive utilization of three- and four-dimensional heteronuclear-edited
      spectra. Sequential assignments of the backbone resonances were made using a
      combination of 15N-edited 3D NOESY-HMQC, 3D TOCSY-HMQC, and 3D TOCSY-NOESY-HSQC
      as well as 3D HNCA, HNCO, and HCACO spectra. Side-chain resonances were assigned
      using 3D HCCH-COSY and 3D HCH-TOCSY spectra. Four-dimensional 13C/13C-edited
      NOESY and 13C/15N-edited NOESY experiments were used to unambigously resolve
      NOEs. The overall global folding pattern was established by calculating a set of
      preliminary structures using constraints derived from the sequential NOEs and a
      small number of long-range NOEs. The beta alpha beta-beta alpha beta domain
      structure exhibits an antiparallel beta-sheet with the conserved RNP 1 and RNP 2
      sequences [Dreyfuss et al. (1988) Trends Biochem. Sci. 13, 86-91] located
      adjacent to one another as the two inner strands of the beta-sheet.

PMID- 1385724
TI  - Stability and photochemical properties of vanadate-trapped nucleotide complexes
      of gizzard myosin in the 6S and 10S conformations: identification of an active
      site serine.
AB  - The properties of divalent metal.ADP.vanadate (V(i)) complexes of the 6S extended
      and 10S folded conformations of gizzard myosin before and after UV irradiation
      have been studied. The half-lives of both 6S and 10S myosin.MgADP.V(i) complexes
      in the dark at 0 degrees C are on the order of 2 weeks. Brief irradiation with UV
      light, however, photomodified the enzyme as suggested by changes in the NH(4+)-,
      K(+)-, and Ca(2+)-ATPase activities, and destabilized the complexes. The 6S
      complex, when irradiated, released ADP and V(i) rapidly (t1/2 less than or equal
      to 1 min) as has been observed in comparable experiments with skeletal myosin
      subfragment 1 (S1) [Grammer et al. (1988) Biochemistry 27, 8408-8415]. The
      irradiated 10S complex released approximately 20% of the ADP and V(i) rapidly
      (t1/2 less than or equal to 1 min), but the remainder stayed trapped, possibly as
      the vanadyl (VO2+).ADP complex, for much longer times (t1/2 approximately 8 h).
      The site of photomodification was sought by reducing both photomodified 6S and
      10S myosin with NaB3H4. Amino acid composition analyses identified [3H]serine as
      the only labeled residue(s), suggesting that the hydroxymethyl group of serine
      had been oxidized to an aldehyde as shown previously for photomodified skeletal
      myosin S1 [Cremo et al. (1989) J. Biol. Chem. 264, 6608-6611]. The 29-kDa NH2
      terminal tryptic peptide from the heavy chain was found to contain essentially
      all of the [3H]serine. Preparations of 6S and 10S [3H]myosin were digested
      exhaustively with trypsin. An identical [3H]peptide was purified from each
      preparation and its sequence determined to be Glu169-Asp-Gln-Ser-Ile-Leu-(Cys)
      Thr-Gly-[3H]Ser-Gly-Ala-Gly-Ly s183.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385726
TI  - Heteronuclear 1H-15N nuclear magnetic resonance studies of the c subunit of the
      Escherichia coli F1F0 ATP synthase: assignment and secondary structure.
AB  - Nuclear magnetic resonance (NMR) studies of the c subunit of F1F0 ATP synthase
      from Escherichia coli are presented. A combination of homonuclear (1H-1H) and
      heteronuclear (1H-15N) 2D and 3D methods was applied to the 79-residue protein,
      dissolved in trifluoroethanol. Resonance assignment for all the backbone amide
      groups and many C alpha H side-chain protons was achieved. Analysis of inter- and
      intraresidue 1H-1H nuclear Overhauser effect (NOE) data and scalar coupling
      constant information indicates that this protein contains two extended regions of
      predominant alpha-helical character (residues 10-40 and 48-77) separated by an
      eight-residue segment which displays little evidence of ordered secondary
      structure. This model is consistent with information about the molecular motion
      of the protein deduced from 15N-1H heteronuclear NOE data and observed pKa values
      of carboxylic acid groups.

PMID- 1385727
TI  - Fragment E-2 from fibrin substantially enhances pro-urokinase-induced Glu
      plasminogen activation. A kinetic study using the plasmin-resistant mutant pro
      urokinase Ala-158-rpro-UK.
AB  - In a previous study, it was shown that fibrin fragment E-2 selectively promotes
      the activation of plasminogen by pro-urokinase (pro-UK) [Liu, J., & Gurewich, V.
      (1991) J. Clin. Invest. 88, 2012-2017]. In this study, the kinetics of this
      promotion by fragment E-2 was studied. Alanine-158-rpro-UK (A-pro-UK), a
      recombinant plasmin-resistant mutant, was used in order to avoid interference by
      UK generation during the reaction. In some experiments, pro-UK was substituted in
      order to validate the mutant as a surrogate. In the presence of a range of
      concentrations (0-20 microM) of fragment E-2, a linear promotion of the catalytic
      efficiency of A-pro-UK against native Glu-plasminogen was seen which was 245.5
      fold at the highest concentration of fragment E-2 and 450-fold at the highest
      ratio of E-2/plasminogen used. The promotion was largely a function of an
      increase in kcat, since fragment E-2 induced a less than 10-fold reduction in KM
      (8.50-1.40 microM). In contrast to this ligand, epsilon-aminocaproic acid (EACA)
      induced a biphasic promotion of the activation of Glu-plasminogen which was only
      18-fold at maximum. Fragment E-2 did not promote the activation of Lys
      plasminogen, but the catalytic efficiency of A-pro-UK was 19.7-fold greater
      against the open Lys-form than against the closed Glu- form of plasminogen.
      Fragment E-2 had no effect on the amidolytic activity of A-pro-UK or pro-UK,
      suggesting that the promotion of their activities was indirect and related to a
      fragment E-2-induced conformational change in Glu-plasminogen.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1385728
TI  - Proteins derived from platelet alpha granules modulate the uptake of oxidized low
      density lipoprotein by macrophages.
AB  - Activated platelets secrete from their alpha granules a protein-like factor which
      stimulates the uptake of oxidized low-density lipoprotein (Ox-LDL) by
      macrophages. The aim of the present study was to evaluate the effect of three
      purified proteins obtained from platelet alpha granules: platelet-derived growth
      factor (PDGF), platelet factor-4 (PF-4), and beta-thromboglobulin (B-TG), on the
      uptake of Ox-LDL by macrophages. Cellular degradation of Ox-LDL by the J-774 A.1
      macrophage-like cell line, that was preincubated for 18 h at 37 degrees C, with
      increasing concentrations of partially purified PDGF, (designated PDGF-CMS-III)
      was increased by up to 36% in comparison to control cells preincubated without
      PDGF. This effect was due to PDGF-mediated increase in the number of macrophage
      receptors for Ox-LDL. The enhanced uptake of Ox-LDL by PDGF resulted in an
      increase in cellular cholesterol content. Preincubation of macrophages with two
      types of recombinant PDGF dimers (10 ng/ml), revealed that PDGF-BB stimulated Ox
      LDL cellular degradation by 64%, whereas PDGF-AB demonstrated only 34%
      stimulation, in comparison to control cells that were not treated with PDGF. The
      stimulatory effect of PDGF-CMS-III and PDGF-AB were reduced by 20% and 28%,
      respectively, when incubated in the presence of H-7, a specific protein kinase C
      inhibitor. When macrophages were preincubated with B-TG, cellular uptake of Ox
      LDL was reduced by up to 30% at 100 ng B-TG/ml. This effect, however, was
      obtained only when B-TG was present in the incubation medium. Cellular
      degradation of Ox-LDL was not affected by preincubation of the cells with PF-4.
      Pretreatment of PCM with anti-PDGF or anti-B-TG antibodies abolished the effects
      of PCM on Ox-LDL degradation by macrophages. PDGF, thus, may represent the
      protein-like factor present in PCM which stimulates Ox-LDL degradation by
      macrophages, whereas B-TG may have a role in the recognition of PCM particles by
      the macrophage scavenger receptor. Modulation of macrophage cholesterol content
      by proteins secreted from activated platelets may have an important role in foam
      cell formation and atherosclerosis.

PMID- 1385729
TI  - Collateral sensitivity to azidothymidine in methotrexate resistant human leukemia
      cells.
AB  - Resistance to methotrexate (MTX) is a well established clinical problem and
      strategies to circumvent this would obviously be beneficial. The human leukemia
      cell line, CCRF-CEM, was grown in folinic acid to study MTX resistance-reflecting
      more in vivo conditions. A 15.8-fold resistant subline, CEM/MTX, was evolved by
      stepwise increases in MTX exposure. The MTX resistant cell line exhibited both
      increased dihydrofolate reductase (DHFR) activity due to gene amplification as
      well as impaired MTX uptake. An additional mechanism of resistance to MTX was a 2
      fold increase in thymidine kinase (TK). As a result of this increased TK
      activity, the CEM/MTX cells were collaterally sensitive to the nucleoside
      analogue, azidothymidine (AZT). CEM cells resistant to MTX possess properties
      that can be exploited by AZT and these studies may have clinical implications.

PMID- 1385730
TI  - Responses of experimental rat tumours and a mouse colon tumour to flavone acetic
      acid.
AB  - The toxicity in rats and mice and the responses of 5 rat lung tumours, a rat
      rhabdomyosarcoma and a mouse colon tumour to flavone acetic acid, FAA, were
      studied. The LD50 values of FAA in WAG/Rij and BN rats were about 350 and 525
      mg/kg respectively, independent of whether the animals were tumour bearing or
      not. In contrast, the LD50 value of tumour bearing BCBA mice was 50 percent of
      that of non-tumour bearing mice. Neither tumour volume regression nor growth
      delay were observed in the rat tumours growing in syngeneic rats or in nude mice,
      in contrast to the response of colon 38 tumours in mice. Light microscopy
      revealed massive tumour necrosis in the mouse tumour while no significant changes
      were observed in the rat tumours.

PMID- 1385731
TI  - Oral acitretin induces alterations in mouse liver phospholipid composition.
AB  - 3 and 10 mg/kg/day acitretin, a new synthetic retinoid, were orally administered
      to two groups of Ng57Bln mice (12 animals each) respectively, over a period of
      six weeks. Control animals (N = 10) received corresponding quantities of arachis
      oil. Chromatographic analysis and quantitative determination of the isolated
      phospholipid classes revealed statistically significant alterations in the liver
      phospholipid composition of the treated animals under both acitretin dosages,
      which may be associated with changes in the metabolic activity, ionic transport
      and cell-cell interaction of the liver cellular components.

PMID- 1385732
TI  - Modulation of complement activation on hemodialysis membranes by immobilized
      heparin.
AB  - To determine the effects of surface-associated heparin on the capacity of
      hemodialysis membranes to activate complement, cellulose acetate (CA) membranes
      that were untreated and CA membranes that had been coated with heparin (HCA) were
      incubated with C3-depleted serum repleted with radio-labeled C3. Next, the
      proteins in the supernatant and those eluted from the membranes were subjected to
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. C3 activation was
      quantified by determining the radioactivity of the C3a-containing band in the
      gel. Total C3a generation (fluid phase C3a plus membrane-associated C3a) was
      three times greater in the presence of HCA compared with CA. Most (88%) of the
      C3a generated in the presence of HCA, however, was adsorbed onto the membrane
      surface. Consequently, there was more C3a in the CA supernatant than in the HCA
      supernatant. To determine the mechanism by which heparin enhanced alternative
      pathway activity, binding studies with radiolabeled factor B and factor H were
      performed. HCA bound 3.4 times more factor B and 20 times more factor H than did
      CA. The binding of these proteins, however, was not dependent on complement
      activation. Studies designed to test the functional activity of isolated factor H
      and factor B that had been adsorbed to the membrane showed that factor H was
      active on both CA and HCA, whereas factor B was active only on HCA. These data
      demonstrate that heparin immobilized onto CA hemodialysis membrane enhances C3
      activation but produces low levels of C3a in the fluid phase because of high
      surface adsorption of the anaphylatoxin. Heparin appears to augment alternative
      pathway activity by favoring the interactions of factor B with other constituents
      of the amplification C3 convertase of the alternative pathway of complement.

PMID- 1385733
TI  - Thromboxane receptor blockade attenuates chronic cyclosporine nephrotoxicity and
      improves survival in rats with renal isograft.
AB  - The question of whether pharmacological inhibition of the thromboxane A2 activity
      prevents cyclosporine-induced chronic renal dysfunction in a Lewis rat model of
      renal isograft was addressed. Transplanted animals were given a daily oral dose
      of cyclosporine (20 mg/kg; N = 15), cyclosporine (20 mg/kg) and the thromboxane
      A2 receptor antagonist GR32191 (3 mg/kg twice daily, by gavage; N = 15), or the
      vehicle alone (N = 12). Treatments were started the day of kidney transplant, and
      animals were monitored for 1 year. Cyclosporine-treated animals developed renal
      insufficiency, as documented by serum creatinine levels of 0.49 +/- 0.09, 0.95 +/
      0.12, and 1.38 +/- 0.15 mg/dL before and after 6 and 12 months of observation,
      respectively. Cyclosporine and GR32191 used in combination partially but
      significantly prevented the deterioration of renal function (serum creatinine,
      basal, 0.52 +/- 0.06; month 6, 0.68 +/- 0.04; month 12, 0.93 +/- 0.10 mg/dL). At
      the end of the study, GFR, as insulin clearance, was significantly lower in rats
      given cyclosporine (0.28 +/- 0.09 mL/min/100 g) than in rats given cyclosporine
      plus GR32191 (0.45 +/- 0.05 mL/min/100 g) or than in vehicle-treated animals
      (0.56 +/- 0.07 mL/min/100 g). Similar results were obtained for the effective
      RPF, measured as p-aminohippurate clearance. At the same time points, comparable
      to whole-blood cyclosporine levels were found in rats receiving cyclosporine
      alone and in those given cyclosporine plus GR32191. More than 50% of the animals
      on cyclosporine alone died from uremia before the end of the observation period.
      By contrast, rats receiving cyclosporine in combination with GR32191 had a
      prolonged survival.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385734
TI  - The growth hormone-insulin-like growth factor I axis and renal glomerular
      function.
AB  - This study examined whether maneuvers that chronically raise or lower serum
      insulin-like growth factor I (IGF-I), within physiological and pathophysiological
      ranges, will affect glomerular hemodynamics. Pair-fed Munich Wistar rats
      received, for 6 to 7 days, continuous s.c. infusions of human recombinant IGF-I
      (rhIGF-I; 125 micrograms/day), vehicle, or s.c. injection of a synthetic growth
      hormone-releasing hormone antagonist (GHRH-ANT) (N = 7 in each group). Infusion
      of rhIGF-I raised serum IGF-I to about 180% of control values, and GHRH-ANT
      injections lowered serum IGF-I to about 33% of control. The IGF-I infusion
      induced an increase in left kidney weight when expressed in absolute units but
      not when expressed as a percentage of body weight; there was also an increase in
      glomerular volume in the IGF-I treated rats. GFR, single nephron GFR, and single
      nephron plasma flow also rose with IGF-I infusion, and these changes were
      associated with decreased afferent and efferent arteriolar resistance and
      increased glomerular ultrafiltration coefficient. GHRH-ANT injection did not
      affect kidney weight or glomerular volume; however, GFR, single nephron GFR, and
      single nephron plasma flow were reduced in association with an increase in
      efferent arteriolar resistance. There also was a tendency, not significant, for
      the glomerular ultrafiltration coefficient to decrease. The findings that a low
      dose of rhIGF-I, which raised the serum IGF-I only modestly, increased glomerular
      ultrafiltration and that reducing serum IGF-I below control values decreased
      glomerular dynamics suggest that physiological or pathophysiological changes in
      IGF-I may affect and possible help to regulate glomerular function.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1385735
TI  - Analysis of structure and transcriptional activation of an osmotin gene.
AB  - A Nicotiana tabacum gene encoding the basic PR-like protein osmotin was isolated
      and characterized. The gene is derived from the N. sylvestris parent of N.
      tabacum. In cell suspension cultures of tobacco, the osmotin gene was shown to be
      transcriptionally activated by treatment with ABA. Transcriptional activation of
      the osmotin promoter was further investigated in transformed plants carrying
      copies of a fusion of the cloned promoter to the beta-glucuronidase reporter
      gene. In these plants, the osmotin promoter is transcriptionally activated by the
      hormones ABA and ethylene. The sensitivity of the osmotin promoter to ABA applied
      exogenously decreased with age in both roots and shoots of young seedlings. NaCl
      shock also activated the promoter in plant tissues. The osmotin promoter is much
      more active in root tissues than in shoot tissues.

PMID- 1385736
TI  - Asynchronous synthesis of membrane skeletal proteins during terminal maturation
      of murine erythroblasts.
AB  - To study the changes in the synthesis of the major membrane skeletal proteins,
      their assembly on the membrane, and their turnover during terminal red blood cell
      maturation in vivo, we have compared early proerythroblasts and late
      erythroblasts obtained from the spleens of mice at different times after
      infection with the anemia-inducing strain of Friend virus (FVA). Metabolic
      labeling of these cells indicates striking differences between early and late
      erythroblasts. In early erythroblasts, spectrin and ankyrin are synthesized in
      large amounts in the cytosol with proportionately high levels of spectrin and
      ankyrin messenger RNA (mRNA). In contrast, only small amounts of these
      polypeptides are incorporated into the skeleton, which is markedly unstable. In
      late erythroblasts, however, the synthesis of spectrin and ankyrin and their mRNA
      levels are substantially reduced, yet the net amounts of these polypeptides
      assembled in the membrane skeleton are markedly increased, and the membrane
      skeleton becomes stable with no detectable protein turnover. The mRNA levels and
      the synthesis of the band 3 and 4.1 proteins are increased considerably in
      terminally differentiated normoblasts with a concomitant increase in the net
      amount and the half-life of the newly assembled spectrin and ankyrin. Thus, the
      increased accumulation of spectrin and ankyrin at the late erythroblast stage is
      a consequence of an increased recruitment of these proteins on the membrane and
      an increase in their stability rather than a transcriptional upregulation. This
      is in contrast to band 3 and 4.1 proteins, which accumulate in direct proportion
      to their mRNA levels and rates of synthesis. These results suggest a key role for
      the band 3 and 4.1 proteins in conferring a long-term stability to the membrane
      skeleton during terminal red blood cell differentiation.

PMID- 1385738
TI  - Angioplasty standard of practice. Standards of Practice Committee of the Society
      of Cardiovascular and Interventional Radiology.

PMID- 1385737
TI  - Primary structure and in vitro expression of the N. crassa phosphoglycerate
      kinase.
AB  - The primary structure of 3-phosphoglycerate kinase (PGK) from Neurospora crassa
      was determined by sequencing a full-length cDNA. The deduced 418 amino acids
      protein shows a considerable identity to PGKs of other organisms with all the
      residues thought to be important for the function of the yeast enzyme conserved.
      The cloned PGK cDNA could be efficiently expressed in vitro resulting in a
      product with the expected molecular weight.

PMID- 1385739
TI  - Effect of antineoplastic agents on smooth muscle cell proliferation in vitro:
      implications for prevention of restenosis after transluminal angioplasty.
AB  - The effect of several antineoplastic agents on vascular smooth muscle cell
      proliferation was studied in vitro. Both fluorouracil and cytarabine produced
      significant concentration-dependent inhibition of smooth muscle cell
      proliferation in cultured porcine pulmonary artery in vitro, while
      cyclophosphamide stimulated growth. For fluorouracil, inhibition was near maximal
      at a concentration of 13.0 microgram/mL and was seen with both coincubation and 2
      hour preincubation of fluorouracil with quiescent cells. Fluorouracil is a
      promising agent for inhibition of intimal proliferation. Further work is
      warranted to determine its effect in vivo.

PMID- 1385740
TI  - Design and testing of a high-flow autoperfusion catheter: an experimental study.
AB  - An autoperfusion catheter is similar to an angioplasty balloon catheter with side
      holes in the guide-wire lumen proximal to the balloon. When the balloon of the
      autoperfusion catheter is deployed and inflated in an artery, the guide wire is
      removed, and the hub of the guide-wire lumen is capped. The catheter then allows
      passive distal perfusion by using ambient pressure to drive blood into the guide
      wire lumen, through the balloon, and out the end hole. This article discusses the
      requirements and constraints of a high-flow autoperfusion catheter, summarizes
      attempts to modify standard angioplasty catheters for use as an autoperfusion
      catheter, and describes the design and testing of a custom autoperfusion catheter
      capable of delivering approximately 3 mL/sec at physiologic pressures. In a model
      of canine acute renal artery occlusion lasting 90 minutes, the custom
      autoperfusion catheter provided marked protection from acute tubular necrosis
      compared with conventional percutaneous transluminal angioplasty catheters. The
      authors conclude that the high-flow autoperfusion catheter may be useful as a
      temporary stent in cases of rupture, dissection, or penetrating wounds involving
      large arteries.

PMID- 1385741
TI  - Budd-Chiari syndrome with long segmental inferior vena cava obstruction:
      treatment with thrombolysis, angioplasty, and intravascular stents.
AB  - The authors describe a patient with Budd-Chiari syndrome caused by long segmental
      thrombotic obstruction of the inferior vena cava associated with paroxysmal
      nocturnal hemoglobinuria. The patient was successfully treated with a combination
      of local thrombolytic therapy, balloon angioplasty, and placement of Gianturco
      expandable metallic stents.

PMID- 1385742
TI  - Oral contraception affects osteocalcin serum profiles in young women.
AB  - The serum concentrations of osteocalcin (bone Gla protein) were followed by
      continuous blood sampling for 24 h in 9 healthy young women before and during
      treatment with oestrogen/progestogen combinations for oral contraception. There
      were marked fluctuations during the 24 h sampling period, values ranging from 0.5
      to 10.0 ng/ml. Values displayed an apparent circadian rhythm. Daytime values were
      on average lower than nocturnal concentrations. During treatment with oral
      contraceptives there was a significant decrease in osteocalcin levels but
      fluctuations during the 24 h sampling period were still observed. Almost all
      individual values obtained at 30 min intervals were lower during treatment. For
      the whole group the mean osteocalcin concentration decreased by 1.4 ng/ml (p less
      than 0.01) during treatment. In postmenopausal women high serum levels of
      osteocalcin are supposed to reflect increased bone turnover secondary to enhanced
      bone resorption. Oestrogens are known to reduce osteocalcin levels and may reduce
      bone resorption. In healthy young women alternative mechanisms should be
      considered but the reduced osteocalcin serum levels in this short-term study
      indicate that oral contraceptive use may influence bone metabolism.

PMID- 1385743
TI  - Psychotherapy for people with multiple sclerosis.

PMID- 1385744
TI  - Immunisation of children born to mothers positive for anti-HBe.

PMID- 1385745
TI  - New rapid test for prenatal detection of trisomy 21 (Down's syndrome):
      preliminary report.
AB  - OBJECTIVE: To devise and evaluate a rapid screening method for detecting trisomy
      21 (Down's syndrome) in samples of uncultured amniotic fluid cells. DESIGN: Non
      radioactive in situ hybridisation with HY128, a 500,000 base pair yeast
      artificial chromosome probe specific for chromosome 21. Blinded study of 12
      karyotypically normal amniotic fluid samples and eight samples trisomic for
      chromosome 21. SETTING: Cytogenetic and obstetric services at a tertiary referral
      centre, Copenhagen. MAIN OUTCOME MEASURES: Time necessary to complete the test.
      Proportion of cell nuclei containing two and three hybridisation signals in
      karyotypically normal and abnormal amniotic fluid samples. RESULTS: The test
      could be completed within three to four days after amniocentesis. In the normal
      samples a mean of 73% (range 61-82%) of the amniotic cell nuclei showed two
      hybridisation signals and 6% (0-18%) showed three signals. By contrast, among the
      trisomic samples 29% (19-38%) of the nuclei exhibited two signals and 48% (31
      60%) showed three signals. CONCLUSION: The technique clearly distinguished
      between normal and trisomic samples. Prenatal diagnosis with in situ
      hybridisation with chromosome specific probes was fast and may make it possible
      to screen for selected, aneuploidies. However, the technique is still at a
      preliminary stage and needs further evaluation and refinement.

PMID- 1385746
TI  - Testing for Huntington's disease.

PMID- 1385747
TI  - Presymptomatic testing for Huntington's disease in the United Kingdom. The United
      Kingdom Huntington's Disease Prediction Consortium.
AB  - OBJECTIVE: To evaluate the United Kingdom Huntington's disease presymptomatic
      testing programme. DESIGN: Postal questionnaire survey to collect data on all
      tests performed by clinical genetics centres between 1987 and 1990. SETTING:
      Genetic centres providing presymptomatic testing in the United Kingdom. SUBJECTS:
      248 subjects at risk of Huntington's disease who had presymptomatic testing at
      their request. MAIN OUTCOME MEASURES: Sex, age, prior risk, and risk after
      testing. RESULTS: The risk of carrying the Huntington disease gene was reduced
      for 151 (61%) of the applicants and raised for 97 (39%). 158 (64%) of the
      subjects were female and 90 (36%) male. The median age at which the results were
      given was 32.5 years. CONCLUSIONS: The demand for testing was lower than expected
      and may have reached its peak in 1990. The excess of low risk results was not
      fully explained by the age effect. All the genetics centres concerned have agreed
      a common service protocol which requires extensive pre-test counselling and post
      test follow up. The worth of the procedure remains to be decided. The
      availability of a large body of pooled data from all the United Kingdom testing
      centres, which individually are likely to have only a few results, will form a
      valuable resource for monitoring the long term psychosocial impact of testing.

PMID- 1385748
TI  - Increased incidence of coronary disease in people with impaired glucose
      tolerance: link with increased lipoprotein(a) concentrations?

PMID- 1385749
TI  - Vertebral fractures.

PMID- 1385750
TI  - Impaired endothelium-dependent relaxation of dog coronary arteries after
      myocardial ischaemia and reperfusion: prevention by amlodipine, propranolol and
      allopurinol.
AB  - 1. Anaesthetized, open-chest dogs were subjected to 60 min of left circumflex
      coronary artery occlusion followed by 90 min of reperfusion. Endothelium
      dependent and -independent relaxant responses of the isolated coronary arterial
      rings were then investigated. 2. The endothelium-dependent, acetylcholine-induced
      relaxation of ischaemic/reperfused arterial rings was significantly attenuated in
      comparison to control rings (1.9 fold rightward shift, ischaemic/reperfused
      maximum relaxation = 57 +/- 13% of control maximum relaxation; P less than 0.05).
      In contrast, glyceryl trinitrate produced similar relaxant responses in control
      and ischaemic rings. 3. Pretreatment of dogs with either amlodipine (3 micrograms
      kg-1 min-1, i.v.) or propranolol (1 mg kg-1, i.v.) completely prevented the
      postischaemic impairment of endothelium-dependent relaxant responses (100 +/- 3%
      and 90 +/- 5% of control maximum relaxation, respectively). 4. Allopurinol
      pretreatment (25 mg kg-1, p.o. 24 h previously, plus 50 mg kg-1 i.v. 5 min before
      arterial occlusion) partially protected against endothelial dysfunction by
      preventing the ischaemia-induced rightward shift of the acetylcholine relaxation
      curve and increasing the maximum relaxation response (83 +/- 7% of control
      rings). 5. These results confirm that endothelium-dependent coronary vascular
      relaxation is impaired by ischaemia and reperfusion, and that the ischaemia
      induced impairment is reduced by pretreatment with amlodipine, propranolol or
      allopurinol.

PMID- 1385751
TI  - Inhibitory effect of morphine on yawning induced by cholinoceptor and dopamine D2
      receptor activation in rats.
AB  - 1. Bromocriptine (2, 4 and 8 mg kg-1, i.p.), physostigmine (0.05, 0.1 and 0.2 mg
      kg-1, i.p.) and pilocarpine (1, 3 and 5 mg kg-1, i.p.) induced dose-dependent
      yawning in rats. 2. These responses were reduced in a dose-dependent manner by
      pretreatment with morphine. 3. The inhibitory effect of morphine was reversed by
      naloxone. 4. Naloxone alone induced slight but significant yawning. 5. The
      present results suggest that morphine inhibits yawning in rats at an opiate
      receptor downstream from the sites at which cholinoceptor and dopamine D2
      activation induce yawning. The anatomical location of these sites remains to be
      established.

PMID- 1385753
TI  - A new paradiscal injection technique for the relief of back spasm after
      chemonucleolysis.
AB  - Back spasm, or spasm of the back muscles, is the commonest adverse reaction
      encountered after chemonucleolysis. In order to overcome this troublesome
      complication, the authors present a new 'paradiscal injection technique'. After
      the injection of chymopapain into the affected disc, the needle is withdrawn to
      just outside the annulus. Bupivacaine is injected into the paradiscal 'space'
      which acts upon the paravertebral muscles. Eighty consecutive patients have been
      treated by chemonucleolysis with paradiscal injection for pain relief. All
      patients were discharged the same day or the following day and no immediate
      complications occurred. When reviewed 3 weeks later, only three (3.8%) patients
      complained of back pain (which was different in character to that present before
      the injection or was exacerbated by the injection). Pain persisted in the same
      patients until 6 months after the injection but was negligible. None of the
      remaining patients had developed back pain as a result of chymopapain. The
      authors suggest that the addition of paradiscal injection of bupivicaine after
      cymopapain injection can reduce the incidence of spasm of the back muscles. This
      technique is a major contribution to increasing the efficacy of chemonucleolysis
      for the treatment of herniated lumbar disc.

PMID- 1385752
TI  - 8-Hydroxy-2-(di-n-propylamino)tetralin impairs spatial learning in a water maze:
      role of postsynaptic 5-HT1A receptors.
AB  - 1. The effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A
      receptor agonist, on place navigation was studied by use of two spatial tasks in
      a water maze. 2. In the first experiment, rats treated subcutaneously with 100
      and 300 (but not 30) micrograms kg-1 8-OH-DPAT were impaired in their ability to
      locate a hidden platform. The probe test confirmed the impairment of spatial
      navigation but the effect (time spent in the training quadrant) was
      quantitatively different, depending on whether 8-OH-DPAT was administered only
      before each training session, only before the probe test or in both conditions.
      3. In the second experiment, rats received 150 micrograms 5,7-dihydroxytryptamine
      (5,7-DHT) intracerebroventricularly to destroy 5-hydroxytryptamine (5-HT)
      containing neurones and 24 days later were examined for choice accuracy in a two
      platform spatial discrimination task. 4. At 100 (but not 30) micrograms kg-1 8-OH
      DPAT impaired rats' accuracy with no effect on latency and no errors of omission.
      In 5,7-DHT-treated rats, this dose had a greater effect, including errors of
      omission. Sham-operated rats injected with 300 micrograms kg-1 8-OH-DPAT were
      markedly impaired in accuracy but they had longer latencies and made more errors
      than controls. All the effects were increased in 5,7-DHT treated rats. 5. The
      results suggest that, at doses causing no apparent changes in motor behaviour or
      motivation, 8-OH-DPAT impairs spatial navigation by stimulating postsynaptic 5
      HT1A receptors in the rat brain.

PMID- 1385754
TI  - Contralateral thinking.

PMID- 1385755
TI  - Reemergence of spontaneous hypertension in hypoxia-protected rats returned to
      normoxia as adults.
AB  - Five-week-old male spontaneously hypertensive rats (SHR) were either exposed to
      hypoxia or maintained in normoxia. Groups of rats were returned to normoxia after
      8 or 12 weeks exposure to hypoxia while others remained in hypoxia or normoxia
      throughout the study. Subdivisions of the groups were sacrificed 2 or 6 weeks
      after return to normoxia at the same time as were rats continuously exposed to
      either normoxia or hypoxia. Hypoxia attenuated the development of systemic
      hypertension (P less than 0.05); however, this protection dissipated partially
      when rats were returned to normoxia. Norepinephrine concentration was
      significantly elevated and serotonin turnover (5-hydroxyindoleacetic
      acid/serotonin 5HIAA/5HT) was significantly decreased in caudal brainstem of
      hypoxic SHR and both were gradually normalized upon return to normoxia.
      Similarly, left ventricular hypertrophy was attenuated and adrenal catecholamine
      contents were increased with hypoxic exposure. Both gradually normalized upon
      return to normoxia. Mechanisms associated with the development of spontaneous
      hypertension reemerge when adult, previously hypoxic SHR are returned to a
      normoxic environment. These findings implicate long-term changes in central
      noradrenergic and serotonergic function as components of the cardiovascular
      adaptation to hypoxia which includes hypoxic moderation of spontaneous
      hypertension.

PMID- 1385756
TI  - Effects of childhood hypertension on the heart. The heart and hypertension.

PMID- 1385757
TI  - Use of interventional radiology for hypertension due to renal artery stenosis in
      children.

PMID- 1385758
TI  - Management of the limitations in low-speed rotational transluminal angioplasty:
      technical note.
AB  - The low-speed rotational transluminal angioplasty catheter system (ROTACS) is a
      recently available device for recanalization of occlusions prior to balloon
      angioplasty. The presence of large collaterals originating just proximal to the
      occlusion with an acute angle, and insufficient space between the puncture site
      and the occlusion for placing an introducer sheath are reported to be limitations
      for ROTACS. To avoid the rotating catheter entering the collateral, we propose a
      technique to create a pilot inlet on the proximal aspect of the occlusion. This
      technique was applied successfully in 4 patients. A contralateral approach was
      used in 3 patients, in whom an ipsilateral access was not possible because of the
      insufficient space to place an introducer sheath.

PMID- 1385759
TI  - Identification of a 5-HT1A receptor positively coupled to planarian adenylate
      cyclase.
AB  - The adenylate cyclase system present in particulate fractions prepared from two
      planarian species was tested for sensitivity to various neurotransmitters. While
      dopamine and other catecholamines were ineffective, serotonin was capable of
      stimulating the enzyme. Among the various serotonin agonists tested, only 8-OH
      DPAT resulted effective on the adenylate cyclase activity, thus suggesting the
      presence in planarians of a serotonin receptor of the type 5-HT1A.

PMID- 1385760
TI  - [Laparoscopic treatment of tubal pregnancy using local administration of
      prostaglandin F2 alpha].
AB  - The present study reports on new treatment of tubal pregnancies by laparoscope
      guided intratubal injection of prostaglandin F2 alpha into the affected tube. In
      9 cases treated with PG, the method proved to be successful in 89%, as indicated
      by reduction of human chorionic gonadotropin (hCG) serum values to less than 20
      IU/l. Preoperative serum hCG levels were 137 to 2520 IU/l (mean 1170 IU/l). In 8
      women the serum concentration of beta hCG decreased to less than 20 IU/l in a
      mean time of 12.3 days. One woman needed surgical intervention 8 days after
      treatment as she continued to have abdominal pain. Hysterosalpingography 3 to 6
      months after treatment showed tubal patency on the side of the pregnancy in two
      of three women who were examined. It is concluded that local prostaglandin F2
      alpha treatment is a suitable method for termination of some tubal pregnancies.

PMID- 1385761
TI  - Phase I clinical and pharmacokinetics study of high-dose toremifene in
      postmenopausal patients with advanced breast cancer.
AB  - Toremifene is an antiestrogen that binds strongly to estrogen receptors (ER). A
      total of 19 previously treated postmenopausal women with metastatic breast cancer
      whose performance status was good and whose ER status was positive or unknown
      were studied to determine the maximum tolerated dose of toremifene. Cohorts of
      patients received 200, 300, or 400 mg/m2 p.o. daily until relapse or unacceptable
      toxicity had occurred. Nausea, vomiting, and dizziness were dose-related. Three
      of five patients receiving 400 mg/m2 experienced moderate or severe vomiting and
      another developed reversible disorientation and hallucinations. Mild sweating,
      peripheral edema, vaginal discharge, and hot flushes were encountered at all
      doses. Reversible corneal pigmentation was identified in seven cases but was not
      of clinical importance. The pharmacokinetics of toremifene was studied weekly and
      in detail on day 42 using a high-performance liquid chromatographic (HPLC) assay
      that identified the parent compound and three active metabolites, N
      desmethyltoremifene, (deaminohydroxy)toremifene, and didemethyltoremifene. Steady
      state was achieved at 1-3 weeks. The toremifene area under the curve and the
      maximal concentration were dose-dependent at high doses. The recommended phase II
      dose is 300 mg/m2 p.o. daily.

PMID- 1385763
TI  - Antidiuretic hormone and atrial natriuretic peptide during lower body negative or
      positive pressure in hypertensive patients with and without left ventricular
      hypertrophy.
AB  - Aim of the study was to evaluate the effect of cardiopulmonary receptors
      activation and deactivation on antidiuretic hormone (ADH) and atrial natriuretic
      peptide (ANP) incretion in hypertensive and normotensive subjects. Twenty-one
      male subjects, 7 normotensives and 14 mild hypertensives, 7 without and 7 with
      left ventricular hypertrophy (LVH) were admitted to the study. Each subject
      underwent selective loading and unloading of cardiopulmonary receptors, by
      application of a positive (LBPP) or negative (LBNP) pressure to the lower body.
      Blood samples were taken for measurement of ANP, ADH, PRA, immunoreactive renin,
      aldosterone, noradrenaline and adrenaline. ADH plasma concentration increased
      during cardiopulmonary receptors inhibition, but this increase became
      statistically significant (p less than 0.05) at a step of LBNP (-40 mm Hg), in
      which an involvement of the sinoaortic receptors cannot be excluded. ANP plasma
      levels increased progressively during LBPP (p less than 0.05 at least). These
      changes were significantly reduced in hypertensive patients with LVH.

PMID- 1385762
TI  - Myocardial mechanical, biochemical, and structural alterations induced by chronic
      ethanol ingestion in rats.
AB  - To determine the effects of moderate ethanol consumption on the mechanical,
      biochemical, and structural characteristics of the heart, myocardial mechanical
      performance, contractile protein enzyme activity, and the number and size of
      myocytes were measured in male Fischer 344 rats after the ingestion of 30% oral
      ethanol. Papillary muscles removed from the left ventricle were greater in
      length, weight, and cross-sectional area than the corresponding muscles from the
      right side. However, no differences were found between control and ethanol
      treated myocardium when either the left or right side was compared separately.
      Chronic ethanol ingestion resulted in an increase in resting tension in left
      ventricular muscles, with no alteration in peak developed tension. Moreover, time
      to peak tension was significantly prolonged, whereas a depression was observed in
      the peak rate of isometric tension development. Isotonically, left muscles from
      ethanol-treated rats revealed a prolongation of time to peak shortening and a
      marked depression in the velocity of shortening at physiological loads. No
      changes were noted in muscles from the right ventricle. Contractile protein
      enzyme activity revealed no differences in myofibrillar Mg(2+)-ATPase activity in
      right and left ventricular myocardium between control and ethanol-treated rats in
      the presence of EGTA. However, at physiological activating levels of calcium, an
      upward shift of the myofibrillar Mg(2+)-ATPase activity-calcium curve occurred in
      left myocardium, whereas a depression in this relation was seen in the right
      ventricle. As a result of chronic ethanol intake, a decrease was noted in the
      volume percent of myocardium occupied by myocytes, and that myocyte cell volume
      per nucleus was found to remain essentially constant throughout the various
      layers of the ventricular wall. Importantly, a 14% significant decrease in the
      total number of myocyte nuclei was demonstrated in the left ventricular
      myocardium of rats on chronic ethanol consumption. Thus, chronic but moderate
      alcohol ingestion resulted in depressed contractile performance, alterations in
      myofibrillar Mg(2+)-ATPase activity, and myocyte loss. These events may serve to
      function as preliminary indicators of the onset of heart failure of alcoholic
      origin in this animal model.

PMID- 1385764
TI  - Effect of fatty acid anilides on immune responses of Swiss mice.
AB  - The possible relationship between fatty acid anilides and the toxic oil syndrome
      (TOS) which appeared in Spain in 1981 has been debated during recent years. These
      anilides have been detected as anomalous compound in toxic oils analysed. After
      treatment with one daily dose of 50 mg/kg of oleilanilide (88.86% pure) for 5
      days, animals showed a tendency towards progressive loss of body weight and a
      significant increase in serum concentration of immunoglobulins. The percentage of
      suppressor T cells in spleen diminished significantly compared with the control
      group. Consequently, an increase in the helper T cells/suppressor T cells was
      also observed. The production of IgM and IgG in culture was significantly higher
      than in controls and no differences were seen in IgA synthesis. The functional
      studies of generation of specific IgM, IgA and IgG suppressor cells at variable
      doses of concanavalin A (Con A) showed paradoxical behaviour of suppressor T
      cells generated by low doses of Con A. A similar change occurred at higher doses
      of Con A. These results suggest that low-dose treatment with oleilanilides
      induces an alteration in the immune response in Swiss mice.

PMID- 1385765
TI  - IL-6 enhances the generation of cytolytic T lymphocytes in the allogeneic mixed
      leucocyte reaction.
AB  - Cytolytic T lymphocytes (CTL) require soluble proteins termed lymphokines to
      develop lytic activity. In this report we have studied two of the lymphokines
      involved in the development of CTL during the allogeneic mixed leucocyte reaction
      (MLR). High doses of dendritic cells induced lytic activity from purified CD8+
      cells in both the murine and human MLR. Under these conditions, IL-2 and IL-6
      were endogenously produced and secreted. Antibodies to IL-2 or the IL-2 receptor
      blocked CTL formation; however, anti-IL-6 receptor antibodies only partially
      inhibited the response while anti-IL-6 antibodies were largely ineffective. When
      limiting numbers of antigen-presenting cells were used CTL failed to develop, and
      neither IL-2 nor IL-6 was secreted into the culture supernatant. Although the
      addition of IL-6 to such cultures was ineffective in generating CTL, the
      combination of IL-2 and IL-6 resulted in a 4-5-fold increase in lytic activity
      over that of IL-2 alone. We conclude that in the allogeneic MLR, IL-2 and IL-6
      contribute to the generation of lytically active CD8+ cells, and the effect of IL
      6 is evident when the dose of antigen-presenting cell is limited.

PMID- 1385766
TI  - Intracellular free Ca2+ fluxes and responses to phorbol ester in T lymphocytes
      from healthy elderly subjects.
AB  - A group of healthy elderly subjects (greater than or equal to 75 years) was
      selected by the strict criteria of the SENIEUR protocol, and compared with
      healthy young (less than or equal to 35 years) volunteers. Mitogenic responses of
      peripheral blood mononuclear cells to phytohaemagglutinin and anti-CD3 were
      significantly reduced in the elderly (P less than 0.0002), thereby confirming
      that even though in perfect health, elderly individuals show impaired cell
      mediated immunity. However, no abnormality of intracellular free Ca2+ fluxes
      could be detected in purified T cells from the elderly subjects when stimulated
      with anti-CD3 antibody. Nevertheless, both the proliferative responses of
      purified T cells to phorbol ester and calcium ionophore (Ionomycin) and the
      phorbol ester-induced inhibition of the Ca2+ response were defective in the
      elderly subjects (P less than 0.003 and P less than 0.0002, respectively). These
      data suggest that signal transduction and the generation of second messengers
      proceed normally in T cells from the elderly, but downstream events mediated by
      activation of protein kinase C are dysfunctional.

PMID- 1385767
TI  - Kinetics of cytokine secretion by mononuclear cells of the blood from rheumatoid
      arthritis patients are different from those of healthy controls.
AB  - Mononuclear cells from peripheral blood (PBMC) of rheumatoid arthritis (RA)
      patients and healthy controls were incubated with alpha-CD3. Cytokine secretion
      from 2 h to 72 h of incubation was measured by ELISA. There were no significant
      differences in secretion of T cell derived IL-2 and IL-4 in cultures from RA
      patients and controls. The macrophage-derived cytokines, IL-1 beta and tumour
      necrosis factor-alpha (TNF-alpha) were secreted with a steep increase of
      concentration during the first 16 h of incubation by PBMC from RA patients. PBMC
      from healthy controls secreted both cytokines at a constantly rising rate with a
      maximum for TNF-alpha at 48 h and for IL-1 beta at 72 h. Interferon-gamma (IFN
      gamma) is secreted in significantly reduced concentrations by PBMC from untreated
      RA patients compared with controls. Gold-salt treatment led to a slightly delayed
      and enhanced secretion of TNF-alpha and IL-1 beta, an enhanced secretion of IL-2
      and a restored secretion of IFN-gamma.

PMID- 1385768
TI  - Elevation of activated gamma delta T cell receptor bearing T lymphocytes in
      patients with autoimmune chronic liver disease.
AB  - To study the possible role of T cells bearing the gamma delta T cell receptor
      (TCR) heterodimer in the pathogenesis of autoimmune chronic active hepatitis (AI
      CAH) and primary sclerosing cholangitis (PSC) in children, we measured levels of
      gamma delta+ T cells in the peripheral blood, assessed the proportion of cells
      bearing the disulphide-linked (BB3+) and non-disulphide-linked (A13+) subtypes of
      the receptor, and studied the co-expression of TCR-gamma delta and the activation
      markers HLA-DR and IL-2 receptor (IL-2R), and the memory cell marker CD45RO.
      Percentage levels and absolute numbers of gamma delta +T cells were higher in
      both groups of patients than in controls (P less than 0.01), mainly as a result
      of an increase in both percentage levels and absolute numbers of the A13+ subtype
      (P less than 0.001). Co-expression of IL-2R and TCR-gamma delta was not found in
      controls but was present in some patients with AI-CAH (four out of 17) and PSC
      (six out of 12) at low levels (median 2.3%, range 1.7-5.0%). Expression of HLA-DR
      on gamma delta+ T cells was similar in both groups of patients and controls. The
      majority of gamma delta+ T cells in children with AI-CAH and PSC also expressed
      CD45RO (74.7 +/- 18.4% and 79.8 +/- 24.3%, respectively) at levels significantly
      higher than in controls (53.3 +/- 17.2%, P less than 0.01). These results suggest
      that autoimmune liver diseases in children are associated with an expansion and
      activation of gamma delta+ T cells in the peripheral blood, which may be
      important in the pathogenesis of these disorders.

PMID- 1385770
TI  - [A case of adult onset phosphoglucomutase deficiency].
AB  - A case of 38-year-old male with adult onset phosphoglucomutase (PGM) deficiency
      was reported. The patient was admitted at Kawamura Hospital (Gifu City) for
      evaluation of easy fatiguability and exercise-induced weakness of the extremities
      since he was 20 years old. Physical examination revealed moderate muscle
      weakness, wasting of extremities, bilateral clubbed fingers and hypoesthesia of
      distal portion of extremities. Fasting plasma glucose was low (58 mg/dl). Venous
      concentration of lactate failed to rise after an ischemic forearm exercise test.
      An epinephrine tolerance test revealed hyperglycemic response. Studies of
      anaerobic glycolysis in vitro using muscle homogenates with the substrate between
      glucose-1-phosphate and glucose-6-phosphate showed decreased lactate production.
      Direct assay of individual muscle glycolytic enzymes demonstrated reduction of
      PGM activity (15% of normal, n = 12). Biopsy study with PAS staining of
      quadriceps femoris muscle demonstrated small amount of deeply staining glycogen
      in subsarcolemmal area. Electron microscopic examination revealed muscle
      destruction with small amount of glycogen in subsarcolemmal and intermyofibrillar
      spaces. Sural nerve biopsy showed degeneration of myelinated and unmyelinated
      fibers but there was no apparent accumulation of glycogen. From the clinical,
      biochemical and histopathological evidences, the patient might be a rare case of
      adult onset PGM deficiency.

PMID- 1385769
TI  - Mechanism of transfer of immune complexes from red blood cell CR1 to monocytes.
AB  - Complement receptor 1 (CR1) on primate red blood cells (RBC) binds most
      complement-fixing immune complexes in the circulation. It has been postulated
      that by binding them, RBC keep immune complexes in the intravascular space and
      deliver them to the tissue macrophages of the mononuclear phagocyte system. We
      have developed an in vitro model to study the transfer of RBC-bound immune
      complexes (heat-aggregated IgG and DNA-anti-DNA) to phagocytic cells (human
      monocytes). Transfer of immune complexes from RBC to monocytes occurred
      significantly more rapidly than monocyte uptake of the same immune complexes from
      solution. In the transfer process, complex-bearing RBC were not bound or
      sequestered by the monocytes. To define the monocyte receptors involved in
      binding immune complexes from the RBC surface, monocyte receptors were blocked
      with MoAbs (anti-CR1, anti-FcRII) or EDTA (to block CR3). Monocyte binding of
      immune complexes primarily used CR1 with a small contribution from FcRII, and
      with little or no contribution from CR3 and FcRI. Uptake of immune complexes from
      solution employed the same monocyte receptors as binding of complexes from the
      RBC surface. Immune complexes in solution bound to RBC and to monocytes with
      equally high avidity (approximately 1 x 10(11) l/M), but monocytes expressed a 15
      20-fold greater number of immune complex binding sites. We propose that immune
      complexes distribute between RBC and monocytes according to the binding capacity
      of these cells, such that at equal or high RBC/monocyte ratios as would be seen
      in the circulation immune complexes bind to RBC, but at low RBC/monocyte ratios
      (as would be seen in the sinusoidal circulation of the liver and spleen), most
      immune complexes bind to monocytes. To define the pathway by which immune
      complexes move from RBC to monocytes, their release from RBC CR1 was examined.
      Under various conditions, the dissociation rate was extremely slow, and did not
      increase with the addition of monocyte supernatants. To examine whether factor I
      mediated processing of immune complexes enhances binding of immune complexes to
      monocytes, RBC-bound complexes were released with factor I, and binding of these
      'processed' immune complexes to monocytes was examined. Monocyte binding of these
      processed immune complexes was slower than of control ones; furthermore,
      performance of transfer experiments at 4 degrees C, which significantly shows
      enzymatic processes, did not decrease the rate of immune complex transfer from
      RBC to monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1385771
TI  - Dietary practices, physical activity, and body-mass index in a selected
      population of Down syndrome children and their siblings.
AB  - Thirty sibling pairs, each with one Down syndrome child between the ages of 2 and
      14, were selected from families who had participated in an infant-stimulation
      program. The maternal and paternal educational levels were 14.9 and 16.9 years,
      respectively. The Down syndrome patients and their siblings were compared in
      terms of body-mass index, that is, weight/stature2 (w/s2); activity as measured
      on a questionnaire; and weekly caloric intake. There were no significant
      differences between the Down syndrome children and their siblings in terms of
      w/s2. The Down syndrome patients were less active than their siblings and spent
      significantly more time indoors, showing a preference for indoor activities.
      Caloric intake calculated as percentage of recommended allowance for height was
      somewhat less in the Down syndrome children--88.7%, compared with 95% in the
      siblings--but not significantly so. It is postulated that even though Down
      syndrome patients have been shown to be at risk for obesity, familial and other
      environmental factors, such as dietary control and involvement in physical
      activity, have an influence.

PMID- 1385772
TI  - Low back pain evaluation and management.

PMID- 1385773
TI  - Americans with Disabilities Act: new job rights for the disabled.

PMID- 1385774
TI  - Important roles of N-methyl-D-aspartate receptors in expression of amygdaloid
      kindled seizure demonstrated by intraperitoneal administration of L-aspartate in
      dimethyl sulfoxide.
AB  - Intraperitoneally (i.p.) administered L-aspartate (Asp) (20 mmol/kg) produced no
      behavioral or EEG change in nonkindled rats. Nonkindled rats that received 18,
      19, or 20 mmol/kg Asp, dissolved in 10 or 15% dimethylsulfoxide (DMSO), i.p.
      developed masticatory movement, head nodding, and myoclonic jerks of the limbs,
      followed by wild running and subsequent tonic extension of the whole body. In
      contrast to the effects in nonkindled rats, i.p. injection of Asp 20 mmol/kg in
      15% DMSO in amygdala-kindled rats precipitated electroclinical generalized
      seizures identical to kindled ones. When the kindled amygdala was pretreated with
      2-amino-7-phosphonoheptanoic acid (2-APH), a potent and specific antagonist of N
      methyl-D-aspartate (NMDA) receptors, the Asp/DMSO-induced generalized convulsion
      identical to kindled amygdala seizure was suppressed. 2-APH treatment of the
      contralateral amygdala was without such suppression. The results suggest that (a)
      Asp is ineffective when given alone (when given with DMSO, however, Asp evokes
      generalized seizures identical to kindled ones in amygdala-kindled rats, while it
      induces a qualitatively different generalized seizure in nonkindled rats; (b)
      NMDA receptors of the kindled amygdala play an important role in activation of
      the transsynaptic neurocircuit underlying the expression of kindled amygdala
      seizure; and (c) DMSO is useful in assessing potential central effects of
      compounds that do not readily penetrate the blood-brain barrier (BBB).

PMID- 1385776
TI  - Adenovirus E1a prevents the retinoblastoma gene product from repressing the
      activity of a cellular transcription factor.
AB  - The retinoblastoma (Rb) gene product forms a complex with the cellular
      transcription factor DRTF1, a property assumed to be important for mediating
      negative growth control because certain viral oncogenes, such as adenovirus E1a,
      prevent this interaction and mutant Rb alleles, which have lost the capacity to
      regulate growth, encode proteins that fail to associate with DRTF1. In this
      study, we show that the wild-type Rb protein can specifically repress
      transcription from promoters driven by DRTF1 whereas a naturally occurring mutant
      Rb protein cannot. Furthermore, Rb-mediated transcriptional repression can be
      overridden by adenovirus E1a; this requires regions in E1a necessary for cellular
      transformation. The Rb protein therefore acts in trans to repress the
      transcriptional activity of DRTF1 whereas adenovirus E1a prevents this
      interaction and thus maintains DRTF1 in a constitutively active state. The Rb
      protein and adenovirus E1a therefore have opposite effects on the activity of a
      common molecular target. Transcriptional repression mediated by the Rb protein
      and inactivation of repression by the E1a protein are likely to play an important
      role in mediating their biological effects.

PMID- 1385775
TI  - Differential occurrence of CSF-like activity and transforming activity of Mos
      during the cell cycle in fibroblasts.
AB  - The Xenopus c-mos proto-oncogene product, Mosxe, possesses cytostatic factor
      (CSF) activity to arrest maturing oocytes in metaphase II and has weak
      transforming activity in mouse NIH3T3 cells. We show that Mosxe mutants bearing
      'stabilizing' penultimate N-terminal amino acids are strongly transforming and
      can retard progression through the G2-M phases in Mosxe-transformed cells,
      probably via their CSF activity. On the other hand, a cyclin-Mosxe fusion
      protein, which undergoes abrupt degradation at the end of mitosis and is restored
      to its normal levels only after the G1 phase, transforms cells much less
      efficiently than a mutated cyclin-Mosxe fusion protein that is stable during M-G1
      transition. Moreover, in low-serum medium, cells transformed by the unstable
      cyclin-Mosxe require a long period to enter the S phase, in contrast with the
      rapid entry into the S phase of cells transformed by the stable cyclin-Mosxe.
      These results provide strong evidence that unlike the physiological CSF activity,
      the transforming activity of Mos is exerted in the G1 phase of the cell cycle.

PMID- 1385777
TI  - T cell receptor (TCR) beta chain homodimers on the surface of immature but not
      mature alpha, gamma, delta chain deficient T cell lines.
AB  - Transfected T cell receptor (TCR) beta chain genes are expressed as homodimers on
      the surface of immature (Sci/ET27F) but not on mature (58 alpha-beta-) T cell
      lines which lack TCR alpha, gamma and delta chains. The homodimer on Sci/ET27F
      cells is tightly bound to CD3 delta and CD3 epsilon while the association with
      CD3 gamma and CD3 zeta proteins is rather weak. Crosslinking of the TCR beta
      homodimers resulted in a strong and rapid calcium flux. In 58 alpha-beta- T cells
      the beta TCR chain could be easily visualized intracellularly but was not
      transported to the cell surface. The Scid cell lines considerably facilitate the
      molecular analysis of early differentiation events in the thymus which are likely
      to be regulated by the beta TCR homodimer.

PMID- 1385778
TI  - Isradipine for the treatment of hypertension following coronary artery bypass
      graft surgery: a randomized trial versus sodium nitroprusside.
AB  - In a randomized trial, a calcium antagonist, isradipine (ISR) and sodium
      nitroprusside (SNP) were compared in the management of hypertension in the early
      period following coronary artery bypass grafting (CABG). Patients with a mean
      arterial pressure (MAP) of greater than 100 mmHg were treated with a 6 h i.v.
      infusion of ISR (n = 98) or SNP (n = 100). Mean MAP at baseline was 113 (ISR) and
      112 mmHg (SNP). Blood pressure control (MAP less than or equal to 90 mmHg within
      25 min) was achieved in 92% (ISR) and 84% (SNP), within a mean of 12 and 15 min,
      respectively (P less than 0.01 between groups). At 25 min, mean percentage
      changes from baseline for ISR and SNP were: MAP -24.3% vs. -21.4% (P less than
      0.05), heart rate +4.1% vs. +8.4% (P less than 0.01), rate-pressure-product 
      16.9% vs. -10.6% (P less than 0.001), cardiac index +19.2% vs. +4.6% (P less than
      0.001), stroke volume index +16.1% vs. -1.9% (P less than 0.001), and peripheral
      vascular resistance -35.4% vs. -22.0%, (P less than 0.001). Treatment was
      discontinued before 6 h in 24 patients in each group because of low blood
      pressure. Hypotension (MAP less than 70 mmHg) and tachycardia were less frequent
      with ISR than with SNP. In conclusion, ISR is effective and well tolerated in the
      treatment of hypertension following CABG, and has a haemodynamic profile which
      may be more favourable than that seen after treatment with SNP.

PMID- 1385779
TI  - Characterization of yeast-expressed beta-actins, site-specifically mutated at the
      tumor-related residue Gly245.
AB  - The tumorigenic cell line HUT14 expresses a beta-actin carrying a mutation at
      position 245. In this study, two mutant beta-actins with amino acid changes at
      position 245 replacing the wild-type glycine by an aspartic acid and a lysine
      residue, respectively, were produced in the yeast Saccharomyces cerevisiae,
      purified to homogeneity and characterized with respect to polymerization
      behaviour and interaction with myosin. The major functional effect of these
      mutations appears to be an impaired polymerization, while the interaction with
      myosin seems less influenced. In addition, the results also suggest the presence
      of a Ca(2+)-binding site in the region of residue 245 in actin.

PMID- 1385781
TI  - The catalytic site is located on subunit I of the ATPase from Halobacterium
      saccharovorum. A direct photoaffinity labeling study.
AB  - Nucleotide-binding sites of the ATPase from the halophilic archaebacterium
      Halobacterium saccharovorum were labeled by ultraviolet irradiation in the
      presence of [alpha-32P]ATP. A high-affinity site, located on subunit I (98 kDa),
      was identified as catalytic by the following criteria: ATP bound to subunit I was
      hydrolyzed and the cross-linked nucleotide was ADP; the specificity for ATP or
      ADP compared to that of other nucleotides was high; the tightly bound
      radionucleotide was exchangeable in the presence of excess unlabeled ATP and
      Mg2+; photolabeling of this site and enzyme inhibition due to tightly bound ADP
      were both dependent on the presence of Mg2+ and showed identical Kd values;
      treatment that restored the activity of the ADP-inhibited enzyme also led to the
      release of the tightly bound nucleotide from subunit I. In addition, a non
      catalytic nucleotide-binding site was found, located on subunit II (71 kDa). This
      site did not hydrolyze ATP, its occupation was Mg2+ independent and the affinity
      for ATP and the nucleotide specificity were much lower than that of subunit I. We
      suspect that this site is nonspecific. These results indicate that H.
      saccharovorum ATPase is different from F1-ATPases which contain the catalytic
      site on the second largest subunit, but may be similar to other archaebacterial
      and vacuolar ATPases.

PMID- 1385780
TI  - Multiple binding sites in fibronectin and the staphylococcal fibronectin
      receptor.
AB  - The binding of fibronectin to Staphylococci exhibits the properties of a ligand
      receptor interaction and has been proposed to mediate bacterial adherence to host
      tissues. To localize staphylococcal-binding sites in fibronectin, the protein was
      subjected to limited proteolysis and, of the generated fragments, Staphylococci
      appeared to preferentially bind to the N-terminal fragment. Different fibronectin
      fragments were isolated and tested for their ability to inhibit 125I-fibronectin
      binding to Staphylococci. The results indicate that only the N-terminal region
      effectively competed for fibronectin binding. However, when isolated fragments
      were adsorbed to microtiter wells, we found that two distinct domains,
      corresponding to the N-terminal fragment and to the heparin-binding peptide
      mapping close to the C-terminal end of fibronectin, promoted the attachment of
      both Staphylococcus aureus Newman and coagulase-negative strain of Staphylococcus
      capitis 651. These same domains were recognized by purified 125I-labeled
      staphylococcal receptor, either when immobilized on microtiter wells or probed
      after adsorption onto nitrocellulose membrane. The heparin-binding domain is
      comprised of type-III-homology repeats 14, 15 and 16. To determine which repeats
      participate in this interaction, we isolated and tested repeats type III14 and
      type III16. We found that the major staphylococcal binding site is located in
      repeat type III14. The staphylococcal receptor bound the N-terminal domain of
      fibronectin with a KD of 1.8 nM, whereas the dissociation constant of the
      receptor molecule for the internal heparin-binding domain was 10 nM. Since the
      fusion protein ZZ-FR, which contains the active sequences of fibronectin receptor
      (D1-D3) bound only to the N-terminus, it is reasonable to assume that the
      bacterial receptor may have additional binding sites outside the D domains,
      capable of interacting with the internal heparin-binding domain of fibronectin.

PMID- 1385782
TI  - Synthesis and spectroscopy of membrane receptor proteins. The gamma subunit of
      the IgE receptor.
AB  - The high-affinity receptor for IgE is a tetrameric complex of subunits of the
      type alpha beta gamma 2. We report here conformational studies of the intact
      gamma subunit in trifluoroethanol and water/liposomes by circular dichroism and
      Fourier-transform infrared (FTIR) spectroscopy. In trifluoroethanol, the FTIR
      amide I' frequencies were consistent with two predominant conformational
      components, the beta-turn and alpha-helix, whilst in liposomes consisting of D2O
      and dimyristoylglycerophosphocholine (Myr2GroPCho), three components were
      observed. The third component present may contain some left-handed extended
      helix. Spectral simulation was carried out to demonstrate that the CD spectra
      were consistent with the component conformations identified from FTIR
      spectroscopy. The stimulated CD spectra were in excellent agreement with the
      experimental spectra. The intact gamma subunit conformation in trifluoroethanol
      was shown to possess 72% alpha-helical and 28% beta-turn conformations. In
      water/Myr2GroPCho liposomes the percentage of each conformational component
      present is 37%, 38% and 25% for the alpha-helix, beta-turn and extended
      structures, respectively. Assuming that the transmembrane fragment was alpha
      helical, an excellent correlation was found between this derived alpha-helical
      content in water/liposomes (37%) and from hydrophobicity plots where the
      percentage of amino acids in the transmembrane domain is predicted by others to
      be 34%. It is suggested that the beta-turn detected by CD and FTIR was
      attributable to a 3(10) helix rather than a type I or type III reverse turn.

PMID- 1385784
TI  - Glove use by orthodontists: results of a survey in England and Wales.
AB  - Attitudes to glove wearing during treatment of patients were tested by
      distribution of a questionnaire to 2000 dentists known to be practising under the
      National Health Service regulations in England and Wales. Of the dentists who
      replied, 41 specialist orthodontists, representing approximately one-sixth of all
      orthodontists working in the general dental services in England and Wales, were
      identified. Results indicate that 39 per cent of these orthodontic respondents
      wore gloves routinely for all patients and procedures, while 49 per cent wore
      gloves for some patients or procedures, with 12 per cent never wearing gloves.
      Reasons given by the occasional glove wearers for not wearing gloves routinely
      included loss of tactile sensation, perceived small risk, lack of comfort, and
      restriction of movement. Six per cent of those who replied had experienced skin
      irritation considered to be associated with glove wearing, while latex gloves
      were preferred by 78 per cent of respondents who wore gloves.

PMID- 1385783
TI  - Iso-immune neonatal neutropenia due to an anti-Fc receptor III (CD16) antibody.
AB  - We report a case of transient neonatal neutropenia due to a maternal iso
      immunization against a non polymorphic region of the glycosylphosphatidylinositol
      linked Fc receptor type III (CD16) on granulocytes. The mother's granulocytes
      were typed NA1-negative, NA2-negative and CD16-negative with human and monoclonal
      antibodies whereas her lymphocytes express the CD16 molecule. Expression of other
      markers were comparable to the controls. Flow cytometric analysis showed that
      maternal antibody recognized the granulocytes but not the lymphocytes from blood
      bank donors and that its binding was decreased on normal, phospholipase C
      treated, granulocytes. The binding of commercial CD16 monoclonal antibodies was
      also dramatically decreased on normal granulocytes pre-incubated with maternal
      serum. The CD16 specificity of the antibody was confirmed by negative reactions
      with another CD16-deficient granulocytes. This observation leads us to conclude
      that cell-lineage specific differences of CD16 molecules are recognized by the
      patient's antibody. Moreover, we confirm that the absence of the FcRIII (CD16) on
      granulocytes is not associated with any pathology or susceptibility to infections
      and that, in the children, the blockade of this receptor by the maternal antibody
      only led to moderate neutropenia.

PMID- 1385785
TI  - Effect of diabetes on the cholinergic enzyme activities of the urinary bladder
      and the seminal vesicles of the rat.
AB  - Choline acetyltransferase (ChAT) and acetyl-cholinesterase (AChE) activities were
      determined in the seminal vesicles and in two regions of the urinary bladder, the
      detrusor muscle and sphincter-trigon in control and streptozotocin(STZ)-induced
      diabetic male Sprague-Dawley rats. In this study, STZ was administered (65 mg/kg,
      i.p.) to induce diabetes 14 days prior to sacrifice and enzyme analysis. Diabetic
      rats exhibited significant increase in both ChAT and AChE activities in the
      detrusor compared to the control animals. Significant increases in ChAT activity,
      however, were observed only in the seminal vesicles of diabetic animals compared
      to the control group. AChE activity in the seminal vesicles and sphincter-trigon
      region of the diabetic rats was not altered significantly. These findings suggest
      that urogenital complications associated with diabetes may be related to the
      dysfunction of the peripheral cholinergic system.

PMID- 1385786
TI  - Reduced ability of neutrophils to produce active oxygen species in streptozotocin
      induced diabetic rats.
AB  - We investigated a possible alteration in the ability of neutrophils to produce
      active oxygen species in streptozotocin (STZ)-induced diabetic rats. The
      production of superoxide of the neutrophils was assessed by luminol-dependent
      chemiluminescence (LDCL) after the stimulation by opsonized zymosan. Four days
      after STZ (60 mg/kg, ip) injection, blood glucose level increased by 399 +/- 9
      mg/dl and the LDCL activity was significantly reduced in diabetic rats (control
      group: 5.12 +/- 1.53 KC/min2/10(6) cells, STZ group: 1.10 +/- 0.07 KC/min2/10(6)
      cells, p less than 0.01). At Day 17, blood glucose level was maintained high (598
      +/- 8 mg/dl) and the LDCL activity (1.01 +/- 0.39 KC/min2/10(6) cells) was almost
      at the same level as that of diabetic rats at Day 4. Subcutaneous injection of
      insulin for 10 consecutive days increased the LDCL activity of diabetic rats in a
      dose-dependent manner (vehicle: 0.82 +/- 0.27 KC/min2/10(6) cells, 0.04 U/day:
      1.61 +/- 0.09 KC/min2/10(6) cells, 0.40 U/day: 1.99 +/- 0.47 KC/min2/10(6) cells,
      4.00 U/day: 3.33 +/- 0.43 KC/min2/10(6) cells). The data obtained herein indicate
      that an increased susceptibility to bacterial infection in diabetic rats results
      from impaired neutrophil function to produce active oxygen species.

PMID- 1385787
TI  - The nucleotide sequence of the S RNA of Impatiens necrotic spot virus, a novel
      tospovirus.
AB  - Impatiens necrotic spot virus (INSV) shares a number of properties with tomato
      spotted wilt virus (TSWV), the type species of the genus tospovirus within the
      family Bunyaviridae. INSV, however, differs from TSWV in plant host range and
      serology. In order to define the genomic structure and the taxonomic status of
      this TSWV-like virus, the nucleotide sequence of its genomic S RNA segment has
      been determined. The molecular data obtained demonstrate that, like TSWV, INSV
      has an ambisense S RNA molecule, encoding a non-structural protein in viral sense
      and the nucleocapsid protein in viral complementary sense. The level of
      nucleotide sequence homology between their S RNAs, as well as the divergence in
      amino acid sequence homology of their gene products, confirm previous conclusions
      from serological studies that INSV and TSWV represent distinct virus species
      within the newly created genus, tospovirus.

PMID- 1385788
TI  - A model of the structure of human annexin VI bound to lipid monolayers.
AB  - Annexin VI is an eight repeat member of the annexin family of proteins which are
      both water soluble and bind to negatively charged phospholipids in a calcium
      dependent manner. Here we present a model for annexin VI based on fitting the
      three-dimensional structure of two annexin V molecules (Huber (1990) EMBO J. 9,
      3867-3874) to the two-dimensional stain-excluding density of lipid-bound annexin
      VI (Newman (1989) J. Mol. Biol. 206, 213-219). Both annexin VI lobes could only
      be fitted with their convex faces closest to the lipid monolayer. This supports
      the hypothesis that annexin-lipid binding is mediated by the interaction between
      calcium bound to the loops protruding from the convex protein surface and
      phospholipid headgroups.

PMID- 1385789
TI  - Detection of VAC-beta (annexin-8) in human placenta.
AB  - A 36 kDa calcium/phospholipid binding protein in human placenta was identified as
      VAC-beta (annexin-8) by a combination of immunological and peptide mapping
      analyses. The protein is a minor product in placenta, accounting for less than 1%
      of extracted annexins. From 150 g of tissue, only 100 micrograms of the protein
      was isolated. By anion-exchange chromatography on diethylaminoethyl-cellulose
      annexin-8 coeluted with annexin-3. By gel filtration, the protein chromatographed
      as a broad peak, where half the product eluted as a monomer and half eluted as a
      heterodimer that was associated with a 10 kDa subunit. The combination of annexin
      8 being a minor component in standard annexin preparations and it co-eluting with
      annexin-3 by ion exchange chromatography are likely to account for the failure of
      other labs to characterize the product.

PMID- 1385790
TI  - Ectopic induction of dorsal mesoderm by overexpression of Xwnt-8 elevates the
      neural competence of Xenopus ectoderm.
AB  - The ectoderm of early Xenopus gastrula is competent to become induced to neural
      tissue, but dorsal ectoderm is more neural competent than ventral ectoderm. It is
      a tenable, but as yet untested possibility that the higher neural competence of
      dorsal gastrula ectoderm is dependent on the presence of the dorsal mesoderm. To
      test this hypothesis we overexpressed Xwnt-8 in order to ectopically induce
      dorsal mesoderm in the ventral side of the embryo. We found that this elevated
      the level of neural competence of ventral ectoderm to that of dorsal ectoderm.
      The effect of Xwnt-8 on neural competence of ventral ectoderm was strictly
      correlated with its ability to enhance the amount of dorsal structures. The data
      indicate that the presence of dorsal mesoderm is a prerequisite for establishing
      the differences in neural competence between gastrula dorsal and ventral
      ectoderm.

PMID- 1385791
TI  - Role of atrial natriuretic peptide in the pathogenesis of sodium retention in
      IDDM with and without glomerular hyperfiltration.
AB  - The pathogenetic determinants of sodium retention in IDDM are not fully
      understood. The aim of this study was to elucidate the action of ANP in 11 IDDM
      patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2),
      referred to here as HF patients; in 10 IDDM patients with normal GFR (greater
      than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients;
      and 12 control subjects, here called C subjects, at baseline and during saline
      infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1;
      Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin
      glucose clamp. C subjects and both HF and NF IDDM patients received a second
      Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at
      euglycemic levels. HF and NF patients were studied again after 3 mo of treatment
      with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor
      without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher
      plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF,
      34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic
      response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS
      vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P
      less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to
      Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had
      still lower urinary sodium excretion rates. The simultaneous administration of
      ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF
      and NF patients. However, urinary sodium excretion rate was significantly lower
      in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and
      NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During
      simultaneous administration of ANP and Saline 1, GFR and FF increased in C
      subjects, but not in HF and NF patients. HF and NF patients had higher urinary
      vasodilatory prostanoid excretion rates than C subjects at baseline. Saline
      infusion did not change urinary excretion rate of prostanoids either in C
      subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1385792
TI  - Screening for cardiovascular disease.

PMID- 1385794
TI  - Ribosomal DNA is a site of chromosome breakage in aneuploid strains of
      Neurospora.
AB  - In wild-type strains of Neurospora crassa, the rDNA is located at a single site
      in the genome called the nucleolus organizer region (NOR), which forms a terminal
      segment on linkage group (LG) V. In the quasiterminal translocation strain
      T(I;V)AR190, most of the right arm of LG I moved to the distal tip of the NOR,
      and one or a few rDNA repeat units are moved to the truncated right arm of LG I.
      I report here that, in partial diploid strains derived from T(I;V)AR190, large
      terminal deletions result from chromosome breakage in the NOR. In most of these
      partial diploids, chromosome breakage is apparently frequent and the breakpoints
      occur in many parts of the NOR. The rDNA ends resulting from chromosome breakage
      are "healed" by the addition of new telomeres. Significantly, the presence of
      ectopic rDNA creates a new site of chromosome breakage in the genome of partial
      diploids. These results raise the possibility that, under certain conditions,
      rDNA is a region of fragility in eukaryotic chromosomes.

PMID- 1385793
TI  - Meiotic recombination on artificial chromosomes in yeast.
AB  - We have examined the meiotic recombination characteristics of artificial
      chromosomes in Saccharomyces cerevisiae. Our experiments were carried out using
      minichromosome derivatives of yeast chromosome III and yeast artificial
      chromosomes composed primarily of bacteriophage lambda DNA. Tetrad analysis
      revealed that the artificial chromosomes exhibit very low levels of meiotic
      recombination. However, when a 12.5-kbp fragment from yeast chromosome VIII was
      inserted into the right arm of the artificial chromosome, recombination within
      that arm mimicked the recombination characteristics of the fragment in its
      natural context including the ability of crossovers to ensure meiotic
      disjunction. Both crossing over and gene conversion (within the ARG4 gene
      contained within the fragment) were measured in the experiments. Similarly, a 55
      kbp region from chromosome III carried on a minichromosome showed crossover
      behavior indistinguishable from that seen when it is carried on chromosome III.
      We discuss the notion that, in yeast, meiotic recombination behavior is
      determined locally by small chromosomal regions that function free of the
      influence of the chromosome as a whole.

PMID- 1385795
TI  - Construction and expression of diphtheria toxin-encoding gene derivatives in
      Escherichia coli.
AB  - We reported earlier that in the periplasmic space of Escherichia coli, truncated
      derivatives of diphtheria toxin undergo limited proteolysis [Zdanovsky et al.,
      Mol. Biol. 22 (1988) 1037-1293]. Here, we present data indicating that this
      proteolysis is reduced in cells bearing a mutation in the degP gene. We have also
      constructed hybrid genes whose products are not secreted into the periplasm.
      These hybrid genes were expressed in E. coli from both the pR promoter,
      controlled by the heat-inducible CI857 repressor, and from the P(lac) promoter,
      controlled by the IPTG-inducible LacI repressor. The latter system proved to be
      more productive.

PMID- 1385796
TI  - T-cell repopulation following neonatal injection of non-obese diabetic (NOD) mice
      with anti-T-cell antibodies.
AB  - Non-obese diabetic (NOD) mice injected with CD3 antibody as newborns have a
      reduced incidence of diabetes, raising the possibility that the neonatal
      injection caused a long-lasting change in circulating T cells. The present study
      shows that NOD and BALB/c mice injected with soluble CD3 antibody in the first 2
      days of life sustained an 80-95% reduction in the number of circulating T cells
      lasting for 2-3 weeks, with T cells returning after 4 weeks, and reaching control
      values after 6 weeks. The T cells which appeared in intact mice 4-6 weeks after
      injection showed no excess of T-cell receptor (TcR) delta expressing cells. They
      had a similar distribution into CD4 and CD8 subsets as uninjected controls, and a
      similar usage and cell surface expression of four T-cell receptor V beta
      families. Labelled CD3 antibody was detected in the serum for up to 2 weeks after
      injection into neonates and was enriched in the thymus. Adoptively transferred T
      cells continued to be cleared from the circulation for 4 weeks following antibody
      injection. The properties of T cells which had been exposed to CD3 neonatally
      were investigated in animals who were first injected with CD3 antibody and then
      thymectomized. These animals had reduced numbers of T cells at 12 weeks of age.
      The surviving T cells showed a Ca2+ flux when stimulated but their proliferation
      in response to concanavalin A (Con A) was reduced, even in the presence of
      irradiated accessory cells or T-cell supernatant co-stimulator factors. Although
      the representation of four different V beta families was the same as in the
      uninjected controls, the density of expression of the T-cell receptor was
      reduced. The data indicate that the limited number of T cells which survive the
      injection are functionally deficient and that an intact thymus is required for
      full T-cell repopulation following neonatal CD3 injection into NOD mice.

PMID- 1385798
TI  - Immunosuppressive activity induced by nitric oxide in culture supernatant of
      activated rat alveolar macrophages.
AB  - Alveolar macrophages (AM) from normal rats had immunosuppressive activity to
      mitogen-induced proliferative responses of splenic lymphocytes. We studied the
      mechanism and the implication of the nitric oxide synthetase pathway in AM
      mediated suppression of concanavalin A (Con A)-induced lymphocyte proliferation.
      The culture supernatant from AM cultures alone did not have immunosuppressive
      activity to Con A-induced proliferative responses of non-adherent spleen cells (n
      ad SC), but the culture supernatant from co-culture of AM and autologous n-ad SC
      had this activity. Con A-pulsed AM also liberated the immunosuppressive factor.
      When AM and autologous n-ad SC were cultured separately under the condition that
      medium could freely communicate, the culture supernatant did not suppress the Con
      A-induced proliferative response of n-ad SC. This indicated that the
      immunosuppressive factor was liberated when AM was activated by cell-to-cell
      contact with n-ad SC. Further, we examined the immunosuppressive activity of the
      culture supernatant of co-culture of AM and autologous n-ad SC to Con A-induced
      responses of allogeneic n-ad SC and xenogeneic murine n-ad SC, and allogeneic
      mixed leucocyte reaction, and found that this culture supernatant could suppress
      all these proliferative responses. Nitrate (NO2-) synthesis was markedly
      augmented in the culture supernatants of Con A-pulsed AM and co-culture of AM and
      n-ad SC. NG-monomethyl-L-arginine (MMA), a specific competitive inhibitor of the
      nitric oxide synthetase pathway (NOSP), extinguished both NO2- synthesis by AM
      and AM-mediated immunosuppressive activity. These data suggest that NOSP was
      important in AM-mediated suppression of Con A-induced lymphocyte proliferation.

PMID- 1385799
TI  - Lower back pain. Laminectomies, spinal fusions, demographics, and socioeconomics.
AB  - The models and analyses used in this study represent an important step in the
      continued search for the optimum use of surgery for the treatment of lower back
      pain. The likelihood of patients who are hospitalized with lower back pain in
      Massachusetts receiving either laminectomies or spinal fusions or both was
      increased when any of the following demographic, socioeconomic, or medical
      characteristics were present: white, male, well insured, young, routine
      admission, admitted to a medium-sized hospital, admitted to a teaching hospital,
      admitted to a hospital with a high occupancy rate, and discharged home.

PMID- 1385797
TI  - Differential effects of pentoxifylline on the production of tumour necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by monocytes and T cells.
AB  - Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production
      of tumour necrosis factor-alpha (TNF-alpha) by monocytic cells. In this study, we
      found that PTX differentially regulates the production of TNF-alpha and
      interleukin-6 (IL-6). Indeed, PTX at high concentrations triggers the production
      of IL-6 but not of TNF-alpha by peripheral blood mononuclear cells (PBMC).
      Further experiments indicated that monocytes are responsible for this PTX-induced
      IL-6 production. When PBMC were stimulated with LPS, PTX was found to inhibit the
      secretion of TNF-alpha as well as the accumulation of TNF-alpha messenger RNA
      (mRNA). In contrast, no inhibitory effect was observed on the induction of IL-6.
      Similar results were obtained when PBMC were stimulated with OKT3 monoclonal
      antibody (mAb). In addition, the in vivo administration of PTX in transplant
      patients receiving the first dose of OKT3 allowed to decrease the systemic
      release of TNF-alpha but not of IL-6. Since monocytes represent a major source of
      TNF-alpha and IL-6 in these settings, additional experiments were performed in
      vitro on purified T cells stimulated with the CLB-T3/3, an anti-CD3 mAb which
      does not require the presence of accessory cells to activate T cells. In this
      system, PTX was found to inhibit the secretion of both TNF-alpha and IL-6 by T
      cells. We suggest that cAMP could be involved in these differential effects of
      PTX on production of TNF-alpha and of IL-6.

PMID- 1385800
TI  - [Bisphosphonates. Drugs for the treatment of disorders of calcium and bone
      metabolism].

PMID- 1385801
TI  - Abdominal guarding.

PMID- 1385802
TI  - Evaluation of 99mTc-mercaptoacetyltripeptides in mice and a baboon.
AB  - Different derivatives of MAG, carrying amino acids such as D- or L-alanine, D
      serine, D-2-aminobutyric acid, D-valine or D-phenylglycine were synthesized and
      their 99mTc-complexes were evaluated in mice and a baboon. The efficiency of
      renal handling of the examined 99mTc-complexes is influenced not only by their
      lipophilicity but also to a great extent by their configuration and the site of
      substitution. The renal excretion characteristics of 99mTc-MAGAG-DA are superior
      to those of 99mTc-MAG3 and the studied 99mTc-complexes in both animal species. In
      an attempt to improve the renal handling of 99mTc-MAG3 and to evaluate the effect
      of derivatization we have synthesized different derivatives of MAG3 in which one
      or more glycyl groups are replaced by other amino acids such as D- or L-alanine,
      D-serine, D-2-aminobutyric acid, D-valine or D-phenylglycine. Due to the presence
      of a chiral centre in the ligand core, exchange labelling of each of the MAG3
      derivatives results in the formation of two diastereomeric technetium complexes.
      These isomers were separated by HPLC and evaluated in mice. Biodistribution in
      mice indicates that the efficiency of renal handling of the examined 99mTc
      complexes is not only influenced by their lipophilicity but also to a great
      extent by their configuration. The renal excretion characteristics of isomer DA
      of 99mTc-MAGAG in mice are superior to those of all other studied 99mTc-complexes
      and also of the reference compound [131I]Hippuran. The isomers LB of several
      alanyl derivatives of 99mTc-MAG3 exhibit a pronounced renal retention in both
      mice and baboon. The results of the evaluation in a baboon confirm the
      superiority of 99mTc-MAGAG-DA over 99mTc-MAG3 and the other studied 99mTc
      complexes.

PMID- 1385803
TI  - Reproductive hormones and bone mineral density in women runners.
AB  - We examined the relationships among reproductive hormone concentrations and bone
      mineral density (BMD) in 43 women runners classified as eumenorrheic (n = 24),
      oligomenorrheic (n = 8), or amenorrheic (n = 11). Results were compared with a
      eumenorrheic nonrunner control group (n = 11). Serum 17 beta-estradiol,
      progesterone, and dehydroepiandrosterone sulfate concentrations were determined
      in daily blood samples for 21 days, and integrated concentrations (areas under
      the curve) were calculated. BMD was assessed at the lumbar spine and proximal
      femur by dual-photon absorptiometry. As expected, 17 beta-estradiol,
      progesterone, and lumbar spine BMD were higher in the control and eumenorrheic
      runner groups than in the oligomenorrheic and amenorrheic runner groups (P less
      than 0.05). Progesterone concentration was significantly correlated with lumbar
      spine BMD in the eumenorrheic runners (r = 0.61). None of the steroid hormones
      was significantly related to BMD in the oligomenorrheic/amenorrheic group. The
      present data suggest that circulating levels of gonadal steroid hormones affect
      axial BMD in eumenorrheic runners.

PMID- 1385804
TI  - Daltroban blocks thromboxane responses in the pulmonary vascular bed of the cat.
AB  - The influence of daltroban (BM13.505; SK&F 96148), a thromboxane (Tx) A2-receptor
      blocking agent, on responses to the TxA2 mimics U-46619 and U-44069 was
      investigated in the pulmonary vascular bed of the intact-chest cat under constant
      flow conditions. Daltroban (5 mg/kg iv) had no significant effect on mean
      baseline vascular pressures but significantly decreased responses to the TxA2
      mimics without altering responses to prostaglandin (PG) F2 alpha or PGD2 or the
      PGD2 metabolite 9 alpha, 11 beta-PGF2. Dose-response curves for U-46619 and U
      44069 were shifted to the right in a parallel manner, and daltroban had no
      significant effect on responses to norepinephrine, serotonin, angiotensin II, BAY
      K 8644, endothelin-(ET) 1, ET-2, or platelet-activating factor (PAF). After
      administration of daltroban, responses to U-46619 returned to 50% of control in
      90 min and responses to the PG and TxA2 precursor arachidonic acid were decreased
      significantly. These results suggest that daltroban selectively antagonizes TxA2
      receptor-mediated responses in a competitive and reversible manner. These data
      provide support for the hypothesis that discrete TxA2 receptors unrelated to
      receptors stimulated by PGF2 alpha, PGD2, or 9 alpha, 11 beta-PGF2 are present in
      the pulmonary vascular bed of the cat. The present data suggest that pulmonary
      vasoconstrictor responses to PAF and ET peptides are not dependent on activation
      of TxA2 receptors in the cat.

PMID- 1385806
TI  - Exercise training prevents decline in stroke volume during exercise in young
      healthy subjects.
AB  - Stroke volume (SV) increases above the resting level during exercise and then
      declines at higher intensities of exercise in sedentary subjects. The purpose of
      this study was to determine whether an attenuation of the decline in SV at higher
      exercise intensities contributes to the increase in maximal cardiac output (Qmax)
      that occurs in response to endurance training. We studied six men and six women,
      25 +/- 1 (SE) yr old, before and after 12 wk of endurance training (3 days/wk
      running for 40 min, 3 days/wk interval training). Cardiac output was measured at
      rest and during exercise at 50 and 100% of maximal O2 uptake (Vo2max) by the C2H2
      rebreathing method. VO2max was increased by 19% (from 2.7 +/- 0.2 to 3.2 +/- 0.3
      l/min, P less than 0.001) in response to the training program. Qmax was increased
      by 12% (from 18.1 +/- 1 to 20.2 +/- 1 l/min, P less than 0.01), SV at maximal
      exercise was increased by 16% (from 97 +/- 6 to 113 +/- 8 ml/beat, P less than
      0.001) and maximal heart rate was decreased by 3% (from 185 +/- 2 to 180 +/- 2
      beats/min, P less than 0.01) after training. The calculated arteriovenous O2
      content difference at maximal exercise was increased by 7% (14.4 +/- 0.4 to 15.4
      +/- 0.4 ml O2/100 ml blood) after training. Before training, SV at VO2max was 9%
      lower than during exercise at 50% VO2max (P less than 0.05). In contrast, after
      training, the decline in SV between 50 and 100% VO2max was only 2% (P = NS).
      Furthermore, SV was significantly higher (P less than 0.01) at 50% VO2max after
      training than it was before. Left ventricular hypertrophy was evident, as
      determined by two-dimensional echocardiography at the completion of training. The
      results indicate that in young healthy subjects the training-induced increase in
      Qmax is due in part to attenuation of the decrease in SV as exercise intensity is
      increased.

PMID- 1385807
TI  - What the Americans with Disabilities Act means to the doctor's office.

PMID- 1385805
TI  - A thromboxane mimetic, U-46619, produces plasma exudation in airways of the
      guinea pig.
AB  - Thromboxane A2 (TxA2) has been implicated in airway responses to allergen and in
      the bronchial hyperresponsiveness observed in asthma. Furthermore a TxA2 receptor
      antagonist and a TxA2 synthase inhibitor inhibit plasma exudation in airways
      induced by inhaled platelet-activating factor. To evaluate whether TxA2 has any
      direct effect on plasma exudation in the airways, we studied the effect of a
      stable TxA2 mimetic (U-46619; 2, 20, and 200 nmol/kg iv) on lung resistance (RL)
      and Evans blue dye extravasation (marker of plasma albumin; 20 mg/kg iv) at the
      airway levels of trachea, main bronchi, and proximal and distal intrapulmonary
      airways in anesthetized, tracheostomized, and mechanically ventilated guinea
      pigs. Injection of U-46619 produced an immediate and marked dose-dependent
      increase in RL, which peaked at approximately 30 s. At the highest dose of U
      46619, we also observed a later increase in RL, starting at approximately 3 min
      and reaching a second peak at approximately 8 min. Mean systemic blood pressure
      increased in a dose-dependent manner [maximum 82 +/- 8 (SE) mmHg]. U-46619 also
      produces dose-dependent plasma exudation, measured as Evans blue dye
      extravasation, at all airway levels as well as into the tracheal lumen. Airway
      responses to U-46619 (200 nmol/kg iv) were abolished in animals pretreated with
      the TxA2 receptor antagonist ICI-192605 (0.5 mg/kg iv). We conclude that U-46619,
      despite being a vasoconstrictor, is potent in inducing plasma exudation in
      airways and that this effect is mediated via a TxA2 receptor.

PMID- 1385808
TI  - Leiomyoblastoma of stomach.

PMID- 1385810
TI  - A nonapeptide to the putative F-actin binding site of annexin-II tetramer
      inhibits its calcium-dependent activation of actin filament bundling.
AB  - A synthetic nonapeptide, Val-Leu-Ile-Arg-Ile-Met-Val-Ser-Arg, corresponding to
      residues 286-294 of annexin-II tetramer (A-IIt), was shown to completely inhibit
      the Ca(2+)-dependent bundling of F-actin by this protein. The inhibitory effect
      of the nonapeptide required preincubation with F-actin and was reversed by the
      addition of excess A-IIt. Kinetic analysis suggested that the nonapeptide reduced
      the K(0.5) but not the Vmax of F-actin bundling. In contrast, addition of excess
      nonapeptide to A-IIt-bundled F-actin did not reverse F-actin bundle formation.
      Although the nonapeptide produced a dose-dependent inhibition of A-IIt-dependent
      F-actin bundling, the binding of A-IIt to F-actin was not affected. These results
      identify a domain of A-IIt that is involved in the bundling activity of the
      protein and suggest that this domain binds transiently with F-actin, resulting in
      activation of the bundling activity of A-IIt.

PMID- 1385811
TI  - Protein-protein interaction studied by site-directed mutagenesis.
      Characterization of the annexin II-binding site on p11, a member of the S100
      protein family.
AB  - p11, a member of the S100 protein family, forms a stable heterotetrameric complex
      with annexin II. The p11-binding site of annexin II resides in the N-terminal 14
      residues, which form an amphiphatic alpha-helix with the hydrophobic face
      representing the contact site for p11 (Johnsson, N., Marriott, G., and Weber, K.
      (1988) EMBO J. 7, 2435-2442). We show that a corresponding peptide can be used to
      purify recombinant p11 by affinity chromatography. To map the annexin II-binding
      site on p11, we have produced progressively truncated p11 derivatives by site
      directed mutagenesis. Our analysis reveals that a highly hydrophobic region
      between residues 85 and 91 is indispensable for annexin II-binding. It is located
      in the C-terminal extension, following the second distorted EF-hand. Using a
      series of single amino acid replacements, we have identified individual
      hydrophobic residues, which seem to represent contact points for annexin II. Most
      notably, substitution of tyrosine 85 or phenylalanine 86 by alanine drastically
      reduces the affinity of p11 for annexin II, whereas replacement of these residues
      by tryptophan has no or only a marginal effect. Thus, hydrophobic side chains on
      both annexin II and p11 are involved in complex formation.

PMID- 1385809
TI  - Architecture of the vir regulons of group A streptococci parallels opacity factor
      phenotype and M protein class.
AB  - Group A streptococci have traditionally been categorized into two broad groups
      based on the presence or absence of serum opacity factor (OF). Recent studies
      show that these two groups vary in a number of properties in addition to the OF
      phenotype, including sequence variations in the constant region of the
      antiphagocytic M protein genes, the presence or absence of immunoglobulin G Fc
      receptor proteins, and the presence or absence of multiple M protein-like genes
      situated in a tandem array. The M protein genes (emm) in OF- streptococcal
      strains are known to be part of a regulon of virulence-related genes controlled
      by the trans-acting positive regulatory gene, virR, situated just upstream of
      emm. In OF+ strains, however, the region adjacent to virR is occupied by an M
      protein-related, type IIa immunoglobulin G Fc receptor gene (fcrA), and the
      relative position of emm has not been determined. To further define the vir
      regulon in OF+ streptococci, we used the polymerase chain reaction to show that
      fcrA49 is situated immediately upstream of emm49 in the OF+ type 49 strain CS101.
      This result shows for the first time the separate identity and genetic linkage of
      these two genes in the vir regulon of an OF+ group A streptococcal strain and
      confirms our previous hypothesis that emm49 exists as the central gene in a trio
      of emm-like genes. Additionally, using DNA hybridizations, we found considerable
      sequence divergence between OF- and OF+ group A streptococci in virR and in the
      noncoding sequences between virR and the emm or fcrA expression site. We found,
      however, a high degree of sequence conservation in this region within each of the
      two groups of strains.

PMID- 1385812
TI  - Requirement of hydrophilic amino-terminal residues for granulocyte-macrophage
      colony-stimulating factor bioactivity and receptor binding.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein
      required for the proliferation and differentiation of granulocyte and macrophage
      precursors. Previous investigations have identified regions in human and murine
      GM-CSF that are required for bioactivity. In the present study, alanine
      substitution mutagenesis was undertaken to define more precisely specific amino
      terminal residues in murine GM-CSF that are involved in bioactivity and receptor
      binding. Five double alanine mutants were identified that showed at least 10-fold
      reductions in bioactivity (K14AK20A, K14AE21A, H15AK20A, H15AE21A, K20AE21A).
      Each of these mutants maintained a normal N-linked glycosylation pattern when
      expressed in COS-1 cells, suggesting that native polypeptide backbone
      conformation was preserved. The purified prokaryotic expression products of two
      mutants (K14AE21A and H15AE21A) had a 100-fold decrease in bioactivity and a
      decrease in receptor binding, indicating that the side chains of K14, H15, and
      E21 are required for optimal receptor binding and maximal bioactivity.

PMID- 1385813
TI  - The VPH1 gene encodes a 95-kDa integral membrane polypeptide required for in vivo
      assembly and activity of the yeast vacuolar H(+)-ATPase.
AB  - Yeast vacuolar acidification-defective (vph) mutants were identified using the pH
      sensitive fluorescence of 6-carboxyfluorescein diacetate (Preston, R. A., Murphy,
      R. F., and Jones, E. W. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 7027-7031).
      Vacuoles purified from yeast bearing the vph1-1 mutation had no detectable
      bafilomycin-sensitive ATPase activity or ATP-dependent proton pumping. The
      peripherally bound nucleotide-binding subunits of the vacuolar H(+)-ATPase (60
      and 69 kDa) were no longer associated with vacuolar membranes yet were present in
      wild type levels in yeast whole cell extracts. The VPH1 gene was cloned by
      complementation of the vph1-1 mutation and independently cloned by screening a
      lambda gt11 expression library with antibodies directed against a 95-kDa vacuolar
      integral membrane protein. Deletion disruption of the VPH1 gene revealed that the
      VPH1 gene is not essential for viability but is required for vacuolar H(+)-ATPase
      assembly and vacuolar acidification. VPH1 encodes a predicted polypeptide of 840
      amino acid residues (molecular mass 95.6 kDa) and contains six putative membrane
      spanning regions. Cell fractionation and immunodetection demonstrate that Vph1p
      is a vacuolar integral membrane protein that co-purifies with vacuolar H(+)
      ATPase activity. Multiple sequence alignments show extensive homology over the
      entire lengths of the following four polypeptides: Vph1p, the 116-kDa polypeptide
      of the rat clathrin-coated vesicles/synaptic vesicle proton pump, the predicted
      polypeptide encoded by the yeast gene STV1 (Similar To VPH1, identified as an
      open reading frame next to the BUB2 gene), and the TJ6 mouse immune suppressor
      factor.

PMID- 1385814
TI  - Characterization of the transcription activator protein C1 of bacteriophage P22.
AB  - We cloned, expressed, and purified the positive regulatory protein C1 of the
      temperate phage P22 of Salmonella typhimurium. The purified protein was
      characterized as to its amino acid composition, protein sequence, molecular
      weight, and antigenicity. P22 C1 was shown to be a tetrameric protein composed of
      four identical subunits with M(r) = 10,000. Moreover, we identified and
      characterized two P22 C1-dependent phage promoters, P(RE) and Pa23, whose
      function was completely dependent on C1 both in vitro and in vivo. These two
      promoters share a common TTGCN6TTGC/T motif in their -35 regions, the same motif
      recognized by the analogous phage lambda transcription activator protein cII. P22
      C1 protein bound selectively to this region and centered on the TTGC repeat
      motif. Binding and transcription experiments demonstrated that the two promoters
      respond coordinately to C1 activation. Last, in contrast to lambda cII, the C1
      protein exhibited little cooperativity with Escherichia coli RNA polymerase for
      DNA binding, but because of its stronger inherent binding ability, achieved an
      overall promoter affinity similar to that observed for cII at its cognate
      promoter signals.

PMID- 1385815
TI  - Functional comparisons between isoforms of the sarcoplasmic or endoplasmic
      reticulum family of calcium pumps.
AB  - ATP-dependent calcium pumps that reside in intracellular organelles are encoded
      by a family of structurally related enzymes, termed the sarcoplasmic or
      endoplasmic reticulum Ca(2+)-ATPases (SERCA), which each have a distinct pattern
      of tissue-specific and developmentally regulated expression. A COS-1 cell
      expression system was used to examine the biochemical properties of the isoforms:
      SERCA1 (fast-twitch skeletal muscle). SERCA2a (cardiac/slow-twitch skeletal
      muscle), SERCA2b (ubiquitous smooth- and non-muscle), and SERCA3 (non-muscle).
      Each isoform was expressed efficiently and appeared to be targeted to the
      endoplasmic reticulum. All isoforms displayed qualitatively similar enzymatic
      properties and were activated by calcium in a cooperative manner with a Hill
      coefficient of 2. The quantitative properties of SERCA1 and SERCA2a (the muscle
      isoforms) were identical in all respects. SERCA2b, however, appeared to have a
      lower turnover rate for both calcium transport and ATP hydrolysis. SERCA3
      displayed a reduced apparent affinity for calcium, an increased apparent affinity
      for vanadate, and an altered pH dependence when compared with the other isoforms.
      These properties are consistent with an enzyme in which the equilibrium between
      the E1 and E2 conformations is shifted toward the E2 state.

PMID- 1385816
TI  - The nucleotide binding/hinge domain plays a crucial role in determining isoform
      specific Ca2+ dependence of organellar Ca(2+)-ATPases.
AB  - Several isoforms of organellar Ca(2+)-ATPases have been identified, each of which
      is expressed in a tissue-specific manner. In order to examine the functional
      properties of fast-twitch (SERCA 1a), cardiac/slow-twitch (SERCA 2a), and non
      muscle (SERCA 3) isoforms of the Ca(2+)-ATPase, cDNAs of each type were expressed
      transiently in COS-1 cells. A study of the Ca2+ dependence of Ca2+ uptake showed
      that SERCA 1 and SERCA 2 have identical Ca2+ dependences (K0.5 = pCa 6.87 +/-
      0.03 and pCa 6.87 +/- 0.02, respectively), but SERCA 3 has a lower Ca2+
      dependence (K0.5 = pCa 6.32 +/- 0.03). A study of the ATP dependence of Ca2+
      uptake showed that SERCA 1, 2, and 3 have almost identical ATP dependences.
      Average Hill coefficients derived from Ca2+ uptake curves ranged from 1.7 to 1.8
      for the three isoforms. In order to identify which regions of the linear sequence
      determine this difference in Ca2+ dependence, chimeric Ca(2+)-ATPases between
      SERCA 2 and SERCA 3 were constructed. Chimeric Ca(2+)-ATPases containing the
      nucleotide binding/hinge domain of SERCA 2 had SERCA 2 type Ca2+ dependence, but
      both nucleotide binding/hinge and COOH-terminal transmembrane domains of SERCA 3
      were required for SERCA 3 type Ca2+ dependence. Accordingly, structural
      interactions between the nucleotide binding/hinge and COOH-terminal transmembrane
      domains appear to determine isoform-specific Ca2+ dependences.

PMID- 1385817
TI  - Down-regulation of scatter factor in MRC 5 fibroblasts by epithelial-derived
      cells. A model for scatter factor modulation.
AB  - Scatter factor/hepatocyte growth factor (SF/HGF) is a multifunctional cytokine
      produced by embryonic fibroblasts and other mesenchymal cells that affects the
      growth and/or the movement of certain epithelia. Here we report that expression
      of scatter factor activity by MRC 5 cells, a strain of normal human embryonic
      lung fibroblasts, is greatly reduced as a result of co-culture of these cells
      with SVK14, an SV40-transformed human keratinocyte cell line. Using a cDNA probe
      to the beta chain of human HGF, we have found that the fall in SF activity in MRC
      5/SVK14 co-cultures is accompanied by the loss of SF/HGF transcripts. As the
      inhibition of SF activity coincides with the disappearance of SF/HGF transcript,
      we conclude that inhibition of the SF activity expressed by MRC 5 cells by co
      culture with SVK14 involves transcriptional regulation.

PMID- 1385818
TI  - Severe back pain and leg weakness in a 38-year-old HIV-infected man.

PMID- 1385819
TI  - The systemic vasculitides.
AB  - Taken together, the systemic vasculitides constitute a small but significant
      component in the practice of many primary care physicians. Like most diseases
      with autoimmune aspects, the vasculitides increase in prevalence with age. Of
      paramount importance is careful differentiation, to provide early appropriate
      treatment and to monitor adverse effects.

PMID- 1385820
TI  - Determination of isradipine and its pyridine metabolite in serum by capillary
      column gas chromatography with nitrogen-selective detection.
AB  - A relatively simple, sensitive and precise gas chromatographic method for the
      determination of isradipine, a calcium antagonist of the dihydropyridine type,
      and its main metabolite in serum is described. Using a one-step extraction
      procedure, a wide-bore column and a nitrogen-phosphorus detector, a limit of
      quantitation of 0.5 and 2.0 nM for isradipine and the metabolite was found. No
      interferences from several drugs were observed. The method was successfully used
      in a pharmacokinetic study in hypertensive women during pregnancy.

PMID- 1385821
TI  - Effects of repeated botulinum toxin injections on orbicularis oculi muscle.
AB  - Histologic evaluation was conducted on 12 orbicularis oculi specimens from 11
      patients with essential blepharospasm and Meige's disease who had received an
      average of 11.3 injections of botulinum A toxin over 3.5 years. Denervation was
      demonstrated by the spread of acetylcholinesterase staining on muscle fibers when
      specimens were evaluated within 11 weeks of the last injection. When specimens
      were taken after 12 weeks, spread of acetylcholinesterase was confined to the
      neuromuscular junctions, with little fiber size variability resembling normal
      muscle. Fibrosis seen in three specimens could be correlated to prior surgery.
      Repeated injections of botulinum toxin into human muscle do not appear to cause
      irreversible muscle atrophy or other degenerative changes. Denervation changes
      (fiber size variability, acetylcholinesterase spread) appear to correlate to the
      time interval since the last injection.

PMID- 1385822
TI  - Dental management considerations in children with attention-deficit hyperactivity
      disorder.
AB  - Children suffering from attention-deficit hyperactivity disorder frequently have
      numerous orofacial anomalies of concern to the dentist. Behavioral manifestations
      of the disorder frequently impair the patient's ability to perform home care
      adequately, make dental treatment arduous, and place the patient at risk of
      physical abuse from family and peers. Familiarity with the symptoms and treatment
      of the disorder will better prepare the dentist to meet the needs of this unique
      group of patients.

PMID- 1385823
TI  - Dental management considerations in children who stutter.
AB  - Stuttering is one of the most common speech disorders of childhood. It is
      characterized by involuntary pauses, reiteration and prolongation of sounds and
      syllables. Oral motor incoordination may make provision of dental treatment
      arduous. Familiarity with the verbal and nonverbal manifestations of the disorder
      and with the possible adverse psychosocial implications prepares the dentist best
      to meet the needs of this unique group of children.

PMID- 1385824
TI  - Pediatric dental education and community service: a combined approach.
AB  - Dental educators nationwide have expressed concern regarding the decreasing
      pediatric clinical experience available to undergraduate dental students. Some
      educators have suggested that dental programs should utilize extramural clinics
      and rotations to enhance current patient pools. This paper presents a successful
      clinical program that is designed to 1) augment the dental education of
      predoctoral dental students, and 2) provide dental care for an underserved
      pediatric dental population in an urban community.

PMID- 1385825
TI  - The effect of the temperature and duration of sample storage on the measurement
      of lymphocyte subpopulations from HIV-1-positive and control subjects.
AB  - EDTA-anticoagulated blood samples from 19 HIV-1-positive subjects and 13 healthy
      laboratory worker controls were analysed for three lymphocyte subpopulations
      (CD3, CD4, CD8 T cells) (lysed whole blood method, Becton Dickinson FACScan flow
      cytometer) at 0, 24, 48, 72 and 96 h after venesection, having been stored at
      either 4 degrees C, 12 degrees C, 16 degrees C or 21 degrees C. In samples stored
      at 4 degrees C and 12 degrees C there was a significant fall in both %CD3 and %CD
      4, and a significant rise in %CD8. At 16 degrees C the %CD8 remained stable,
      while there were marginal rises in %CD3 and %CD4. At 21 degrees C, the %CD8 again
      remained stable, while %CD3 and %CD4 rose significantly with time. These trends
      were independent of HIV-1 status. At each temperature studied, the rates of
      change of lymphocyte subpopulations were independent of each other. These results
      suggest that a temperature range of 14-16 degrees C may be optimal for sample
      storage prior to measurement of T cell subsets. They emphasise the importance of
      strict control on conditions if samples are to be kept for any length of time
      before analysis.

PMID- 1385826
TI  - Fc epsilon R11/CD23 receptor distribution in patch test reactions to
      aeroallergens in atopic dermatitis.
AB  - There is increasing evidence that exposure to organic allergens may induce or
      exacerbate lesional skin in patients with atopic dermatitis. In this study,
      patients with atopic dermatitis were patch tested to 11 common organic allergens
      and to control chambers containing 0.4% phenol and 50% glycerin in 0.9% saline.
      In biopsies from positive patch test reactions, patch test control skin, lesional
      eczematous and non-lesional skin from atopic individuals, and normal skin from
      non-atopic volunteers, the presence and distribution of macrophages (RFD7+),
      dendritic cells (RFD1+), and Langerhans cells, and the expression of the low
      affinity receptor for IgE (CD23) were investigated. In patch test reactions and
      lesional skin samples, inflammatory infiltrates of diffusely distributed
      macrophages (RFD7+), dendritic cells (RFD1+), T lymphocytes (RFTmix+), and
      Langerhans cells (CD1+) were seen, the latter being present in both the epidermis
      and the dermis. The numbers of Langerhans cells were reduced in the epidermis and
      increased in the dermis in patch test reactions and lesional skin compared to
      their controls. Double staining revealed a change in the distribution of CD23
      antigen. In patch test control and non-lesional biopsies many macrophages and
      only a few Langerhans cells within the dermal infiltrates expressed this antigen.
      In patch test reaction and lesional skin samples, however, the proportion of
      CD23+ dermal Langerhans cells had increased compared to macrophages. Furthermore,
      in these latter samples an increased proportion of dermal CD1+ cells expressed
      the dendritic cell (RFD1+) marker. These results show that following antigen
      challenge there are marked similarities between the phenotype of the cellular
      infiltrate in patch test reaction and lesional skin biopsies, and also
      demonstrate a changing distribution of CD23 on antigen-presenting cells.

PMID- 1385827
TI  - Relative importance of prior basal cell carcinomas, continuing sun exposure, and
      circulating T lymphocytes on the development of basal cell carcinoma.
AB  - This 36-month prospective study of a group of 61 people at high risk to develop
      multiple basal cell carcinomas (BCC) examined the circulating lymphocyte subsets
      of the population, patterns of sun exposure, and the longitudinal development of
      basal cell carcinoma. Sun exposure status was highly correlated with immune
      status defined by the CD4/CD8 T-lymphocyte ratio. There were significantly more
      BCC at 18 and 36 months in the 35 patients with high sun exposure and low CD4/CD8
      ratio than in the 20 patients with low sun exposure and high CD4/CD8 ratio. A
      multivariate analysis assessed the relative importance of prior basal cell
      carcinoma, sun exposure, and immune status on the development of the skin cancer.
      Basal cell carcinoma developing in the previous 18 months and sun exposure during
      those 18 months were the first and second most important variables in determining
      development of basal cell carcinoma during the next 18 months. CD4/CD8 ratio had
      no additional predictive ability once prior skin cancers and sun exposure were
      accounted for. A low ratio of CD4/CD8 cells correlated with high sun exposure
      during the preceding 18 months.

PMID- 1385828
TI  - The small non-structural protein NS2 of the autonomous parvovirus minute virus of
      mice is required for virus growth in murine cells.
AB  - Mutants of the autonomous parvovirus minute virus of mice (MVM) strains MVM(p)
      and MVM(i) that either fail to produce or produce a truncated NS2 protein, were
      deficient in the production of infectious virus and attained lower levels of
      viral DNA synthesis than wild-type virus following infection of a series of
      normal and transformed murine cell lines. Mutant virus growth and the levels of
      DNA replication were similar to those of wild-type virus in the rat, hamster and
      human lines tested. These results suggest that the requirement of NS2 for the
      growth of MVM is murine species-specific.

PMID- 1385829
TI  - Identification of a novel N-methyl-D-aspartate receptor population in the rat
      medial thalamus.
AB  - To evaluate the possibility of pharmacologically distinct N-methyl-D-aspartate
      (NMDA) receptor subtypes, quantitative autoradiography was used to determine the
      potency of several compounds as inhibitors of L-[3H]glutamate or [3H]MK-801
      binding to rat brain NMDA receptors in 10 brain regions. Competitive NMDA
      receptor antagonists displayed differing pharmacological profiles in the
      forebrain, cerebellum, and medial regions of the thalamus (midline nuclei). For
      example, compared with other competitive antagonists, 3-[(+/-)-2-carboxypiperazin
      4-yl]propyl-1-phosphonate (CPP) and LY-233536 were especially weak displacers of
      L-[3H]glutamate binding in the cerebellum. In the the medial thalamus, CPP and D
      2-amino-5-phosphonopentanoate displayed relatively low affinities, whereas LY
      233536 was relatively potent. The noncompetitive NMDA receptor antagonists also
      displayed regional variations in their pharmacological profiles. Relative to
      other regions, [3H]MK-801 binding in the cerebellum was weakly displaced by MK
      801 and potently displaced by dextromethorphan and SKF-10047. In the medial
      thalamus, 1-[1-(2-thienyl)-cyclohexyl]piperidine was relatively potent and SKF
      10047 was relatively weak. These results confirm previous suggestions that the
      cerebellum contains a distinct NMDA receptor subtype and indicate that nuclei of
      the medial thalamus contain a novel NMDA receptor subtype that is distinct from
      both those found in the cerebellum and in the forebrain.

PMID- 1385830
TI  - Distribution of preproatrial natriuretic peptide mRNA in rat brain detected by in
      situ hybridization of DNA oligonucleotides: enrichment in hypothalamic and limbic
      regions.
AB  - The expression and distribution of mRNA encoding preproatrial natriuretic peptide
      (ppANP) in rat brain has been investigated by in situ hybridization of two 35S
      labeled synthetic DNA oligonucleotides, based on a cDNA clone sequence that
      encodes rat ppANP. The highest relative concentrations of ppANP mRNA were
      detected in the medial preoptic hypothalamic nucleus ("anteroventral/third
      ventricle region") and the medial habenula. Moderate concentrations of ppANP mRNA
      were observed in the CA1 pyramidal cells of the hippocampus, the endopiriform
      nucleus, the arcuate nucleus, the zona incerta, and cells of the pontine
      tegmental and peduculopontine nuclei. Several of these regions, including the
      habenula and the hypothalamic areas, have previously been reported to contain
      atrial natriuretic peptide (ANP)-like immunoreactivity, but the expression of
      ppANP mRNA in CA1 pyramidal cells suggests the occurrence of differential
      translation of ppANP mRNA into protein product in different brain regions, or the
      existence of different immunological forms of the peptide. The abundance of ppANP
      mRNA in brain was relatively low in comparison with that previously reported for
      many other mRNA species encoding other brain neuropeptides. These results
      demonstrate that ANP gene expression occurs in discrete neuronal populations of
      the CNS and that studies of the regulation of this expression should now be
      possible using quantitative in situ hybridization.

PMID- 1385831
TI  - Modification of Pseudomonas aeruginosa virulence factors by sub-inhibitory
      concentrations of antibiotics.
AB  - This study's objectives were to evaluate the effects of subminimum inhibitory
      concentrations (MICs) of tobramycin, gentamicin, netilmicin, streptomycin,
      ciprofloxacin, cefotaxime and piperacillin on proteinase production, alginate and
      siderophore synthesis by two strains of Pseudomonas aeruginosa. One of these
      strains, of recent clinical isolation, was mucoid. In fact it is well known that
      mucoid strains are more resistant than non-mucoid; there is, moreover, evidence
      that in cystic fibrotic lungs the non-mucoid P. aeruginosa are invariably
      replaced by mucoid variants. Our results show that subinhibitory concentrations
      of beta-lactams and quinolones significantly reduced the amount of alginate.
      Protease production was affected by all antibiotics tested.

PMID- 1385832
TI  - Renin-angiotensin system unresponsiveness in phaeochromocytoma.
AB  - Water immersion to the neck is able to provoke a profound suppression of the
      renin-angiotensin system in several clinical conditions associated with hyper
      reninaemia. Both hyper-reninaemia and secondary aldosteronism have sometimes been
      described in phaeochromocytoma. We report on two patients, with surgically proven
      phaeochromocytoma, in whom water immersion, performed before surgery, failed to
      induce any significant change in plasma renin activity.

PMID- 1385833
TI  - A block in full-length transcript maturation in cells nonpermissive for B19
      parvovirus.
AB  - Vertebrate parvoviruses share a similar genomic organization, with the capsid
      proteins encoded by genes on the right side and nonstructural proteins encoded by
      genes on the left side. The temporal and cell-specific appearances of these two
      types of gene products are regulated by a variety of genetic mechanisms. Rodent
      parvovirus structural proteins, for example, are encoded by a separate promoter
      which is positively regulated by nonstructural-gene products. In contrast, for
      the human B19 parvovirus, the analogous structural-gene promoter is
      nonfunctional, and both left- and right-side transcripts originate from a single
      promoter and are highly processed. Using a combination of sensitive RNA analyses
      of wild-type and mutant templates, we have found that the relative abundance of
      these alternatively processed transcripts appears to be governed by unique
      postinitiation events. In permissive cells, the steady-state level of right-side
      structural-gene transcripts predominates over that of left-side nonstructural
      gene transcripts. In nonpermissive cells transfected with the B19 virus genome,
      nonstructural-gene transcripts predominate. Removal of 3' processing signals
      located in the middle of the viral genome increases transcription of the far
      right side. Disruption of a polyadenylation signal in this region makes
      readthrough of full-length right-side transcripts possible. These results suggest
      that the abundance of B19 virus RNAs is determined by active 3' processing and is
      coupled to DNA template replication.

PMID- 1385834
TI  - Role of the adenovirus E3-19k conserved region in binding major
      histocompatibility complex class I molecules.
AB  - The adenovirus early region 3 glycoprotein E3-19k binds to and down regulates
      major histocompatibility complex (MHC) class I molecules in infected cells. We
      previously identified a 20-amino-acid conserved region in E3-19k by comparison of
      protein sequences from four different adenovirus serotypes. The roles of the E3
      19k C-terminal and adjacent conserved regions in the interaction with MHC class I
      molecules have been examined. A functional class I-binding glycoprotein was
      expressed from the cloned E3 18.5-kDa open reading frame of adenovirus type 35.
      Truncations and single-amino-acid mutations in the adenovirus type 35
      glycoprotein were created by site-directed in vitro mutagenesis and tested for
      the ability to associate with MHC class I molecules. Deletion of most of the
      transmembrane domain and cytoplasmic tail did not affect binding to class I
      molecules. However, removal of an additional 11 amino acids eliminated binding
      and changed the conformation of the adjacent conserved region. Separate mutations
      of residues Asp-107 and Met-110, within the conserved region, severely reduced or
      eliminated binding. These data indicate that the E3-19k conserved region plays a
      crucial role in binding to MHC class I molecules.

PMID- 1385835
TI  - High-affinity laminin receptor is a receptor for Sindbis virus in mammalian
      cells.
AB  - Sindbis virus is an alphavirus with a very wide host range, being able to infect
      many birds and mammals as well as mosquitoes. We have isolated a monoclonal
      antibody that largely blocks virus binding to mammalian cells. This antibody was
      found to be directed against the C-terminal domain of the high-affinity laminin
      receptor, a 67-kDa protein present on the cell surface that binds with high
      affinity to basement membrane laminin and that is known to be important in
      development and in tumor invasion. This receptor is believed to be formed from a
      295-amino-acid polypeptide that is modified in some unknown way after
      translation. The primary sequence of this 295-amino-acid protein is highly
      conserved among mammals. We found the hamster amino acid sequence to be identical
      to a mouse sequence and to differ at only two amino acids from a human sequence
      and at two amino acids from a bovine sequence. To verify the importance of the
      laminin receptor for infection by Sindbis virus, hamster cells were stably
      transfected with the gene encoding the 295-amino-acid protein under the control
      of a high-efficiency promoter. Such transfected hamster cells overexpressed the
      laminin receptor at the cell surface, bound severalfold more Sindbis virions than
      did the parental cells, and became infected by Sindbis virus with a higher
      efficiency. In contrast, cells transfected with the antisense gene expressed less
      laminin receptor on the surface and were less susceptible to the virus. Binding
      of the virus varied linearly with the amount of laminin receptor on the cell
      surface, whereas infectivity measured with a plaque assay varied with the 1.4
      power of the receptor concentration, suggesting that interaction with more than
      one receptor aids virus penetration. By these criteria, the laminin receptor
      functions as the major receptor for Sindbis virus entry into mammalian cells. We
      also found that the anti-laminin receptor antibody partially blocked Sindbis
      virus binding to mosquito cells, suggesting that the laminin receptor is
      conserved in mosquitoes and functions as a Sindbis virus receptor in this host.
      The wide distribution of this highly conserved receptor may be in part
      responsible for the broad host range exhibited by the virus, which infects a wide
      range of mammals and birds as well as its mosquito vector and can infect many
      different tissues within these hosts.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1385837
TI  - [A comparison of bronchodilating drugs in the treatment of stable COPD].
AB  - The purpose of this study was to establish the optimal bronchodilating drug among
      therapies currently available for clinical treatment of the stable phase of
      chronic obstructive pulmonary disease (COPD). The efficacy of ipratropium bromide
      40 micrograms, salbutamol 200 micrograms, and ipratropium bromide 40 micrograms
      plus salbutamol 200 micrograms was compared in 14 patients with COPD. Daily PEFR
      was obtained during the last seven days of a 2 week period incorporating drug
      inhalation four times daily. FEV1 and FVC were assessed on the final day of the
      treatment period. In the absence of bronchodilating medication, FEV1 was 1.27 +/-
      0.13 l (52.9 +/- 5.1% pred). With ipratropium bromide 40 micrograms alone, FEV1
      was 1.43 +/- 0.13 l (59.8 +/- 5.3% pred). A similar value was obtained for
      salbutamol 200 micrograms: 1.45 +/- 0.14 l (61.0 +/- 5.4% pred). However, FEV1
      following the administration of ipratropium bromide 40 micrograms in combination
      with salbutamol 200 micrograms was 1.51 +/- 0.13 l (63.6 +/- 5.3% pred). The
      percent increase in FEV1 (compared to the value obtained without medication) was
      significantly higher with combined ipratropium bromide 40 micrograms plus
      salbutamol 200 micrograms (122.2 +/- 3.8%) than with either ipratropium bromide
      40 micrograms (114.8 +/- 5.5%) or salbutamol 200 micrograms (116.5 +/- 4.4%)
      alone. Furthermore, the daily post-dilator PEFR improved significantly more with
      the combined therapy four times a day (311 +/- 29 l/min) than with either
      ipratropium bromide 40 micrograms (296 +/- 30 l/min) or salbutamol 200 micrograms
      (303 +/- 29 l/min) therapy alone. There was no discernible difference between
      results obtained with ipratropium bromide 40 micrograms versus salbutamol 200
      micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385836
TI  - [Induction of tubular basement membrane (TBM) antigen specific suppressor T cells
      in BALB/c mice].
AB  - Transfer of tubular basement membrane (TBM)-primed thymocytes from BALB/c mice
      that had been immunized with allogeneic TBM antigen without adjuvant prevented
      the development of interstitial nephritis (IN) in recipient BALB/c mice that had
      been immunized with TBM antigen with complete Freund's adjuvant (CFA) to produce
      IN. TBM antigen was prepared from TBM of normal ddY mice (ddY TBM antigen).
      BALB/c mice were highly susceptible to IN and showed a high immune response to
      TBM antigen when they were immunized with TBM antigen in CFA. Development of IN
      in high responder BALB/c mice was clearly suppressed by transfer with ddY TBM
      thymocytes. The anti-TBM antibody response and the proliferative response of
      splenic T cells to TBM antigen were also depressed by the transfer. The cell
      extract of ddY TBM-thymocytes had also suppressive activity on the development of
      IN and on the immune response to TBM antigen. This simple system without any
      adjuvant for inducing the thymocytes, which has strong suppressive activity on
      the development of IN and on the immune response to TBM antigen, may allow us to
      analyse the role of suppressor T cells in negative regulation of IN.

PMID- 1385838
TI  - Are cardiac and vascular "amplifiers" both necessary for the development of
      hypertension?
AB  - The vascular amplifier leads to enhancement of all resistance responses, from
      full dilatation to maximum constriction. The mechanism of resistance
      amplification is narrowing of the resistance vasculature, which is approximately
      constant at all levels of vasomotor tone. From the literature, the site of
      narrowing is localized to the small arteries and large arterioles. The narrowing
      at rest leads during constriction, to patchy reduction in blood flow in the
      microcirculation. The enhanced resistance responses of the vascular amplifier
      during constriction, increase blood pressure (BP) upstream, which minimizes the
      hemodynamic effects on the microcirculation and helps to maintain venous return.
      Concentric left ventricular (LV) hypertrophy is an amplifier of stroke volume and
      cardiac output. It reinforces the elevation of BP upstream from the site of
      vascular narrowing. This appears important for the initiation and maintenance of
      hypertension, in view of findings in SHR showing: (1) that in the course of
      normal development of hypertension the vascular amplifier properties develop
      before the onset of hypertension, which occurs in parallel with an increase in
      rate of LV hypertrophy; (2) after brief periods of enalapril treatment,
      hypertension redevelops in parallel with the redevelopment of LV hypertrophy,
      whilst the vascular amplifier properties remain suppressed; (3) treatment with
      immuno-sympathectomy plus prazosin prevents the development of both LV
      hypertrophy and hypertension but only produces gradual suppression of the
      vascular amplifier properties. The role of the sympathetic nervous system on LV
      hypertrophy is mediated through alpha 1-adrenoceptors.

PMID- 1385839
TI  - Remodeling of the heart (membrane proteins and collagen) in hypertensive
      cardiopathy.
AB  - The basis for impaired left ventricular function of hearts in moderate to severe
      stages of hypertrophy and congestive heart failure remains uncertain. At the
      cellular level, the mechanisms governing the movements of calcium in the
      myocardium are actually depressed and might at least in part account for the
      slowing of the maximum shortening velocity and the impaired relaxation. These
      alterations of membrane proteins seem particularly important in species where the
      slowing of Vmax cannot be a consequence of the myosin heavy chain shift. They
      lead to an unstable equilibrium of calcium homeostasis and to calcium overload in
      heart failure. On the other hand, the enhanced density and remodeling of collagen
      in the hypertrophied heart, which would depend on elevation in circulating
      aldosterone, impair myocardial stiffness with diastolic dysfunction and lead to
      altered pumping capacity of the heart. Disturbances of calcium metabolism and
      matrix collagen remodeling enhance early afterdepolarizations and arrhythmias.

PMID- 1385840
TI  - Angiotensin II, vascular structure and blood pressure.
AB  - Angiotensin II (Ang II) in low dose raises blood pressure slowly by a mechanism
      which is not understood, but which is clearly different from the better known
      direct vasoconstrictor effect. Vascular hypertrophy develops during this slow
      pressor response, but is not wholly a consequence of the increase of pressure. We
      discuss non-pressor mechanisms by which Ang II may act as a growth factor to
      promote structural vascular change. Studies with cultured vascular smooth muscle
      cells suggest at least three possibilities, but none of these has been tested in
      vivo during slow pressor infusion of Ang II. The action of growth factors may be
      important in hypertension since increased arterial pressure causes vascular
      hypertrophy. Growth factors influence markedly the extent of this hypertrophic
      response and, however produced, vascular hypertrophy has an important influence
      on resistance and arterial pressure in hypertension.

PMID- 1385841
TI  - [Characteristics of surgical interventions on account of uncomplicated duodenal
      ulcers].
AB  - The peculiarities of performance of the operative intervention for duodenal ulcer
      in 291 patients are presented. The technical difficulties encountered at the time
      of operative intervention in uncomplicated course of the disease can be
      conditioned by constitution of a patient, or peculiarities of the pathological
      process. It is expedient to conduct the operative treatment of the patients with
      an uncomplicated duodenal ulcer at a specialized therapeutic institution, where
      the choice of a type for forthcoming operation is made on the basis of the
      findings of preoperative examination, and operative intervention is performed by
      the highly qualified experts.

PMID- 1385842
TI  - [Tactics of the surgical treatment of acute intestinal obstruction].
AB  - The results of treatment of 184 patients with acute ileus of non-tumour genesis
      operated on at the clinic within the period of from 1981 to 1990 are presented.
      In elimination of ileus without the surgical intervention, together with
      intensive therapy, intestinal decompression was used. Of 19 patients with acute
      ileus associated with peritonitis operated on, 12 underwent resection of the
      intestine. The use of enterosorption as well as extracorporeal hemosorption
      contributed to elimination of endogenous intoxication.

PMID- 1385844
TI  - [The treatment of pneumothorax and hemothorax in multiple rib fractures and
      associated trauma].
AB  - The results of treatment of 480 sufferers with multiple costal fractures and
      associated trauma to the chest were analysed. Resulting from trauma, 55 (25.5%)
      patients developed pneumothorax, 71 (32.8%)--hemothorax, 90 (41.7%)-
      hemopneumothorax. Treatment of pneumo- and hemothorax in most cases was
      conservative (puncture of the pleural cavity was usually performed, rarely--its
      drainage). In 47 sufferers with associated trauma who were at a forced position
      (lying on their back), the aimed catheterization of the pleural cavity by means
      of the trocar stilette curved under the angle of 60 degrees was used. For the
      treatment of clotted hemothorax, the streptokinase was used with a positive
      effect noted in 6 of 7 patients. Indications for thoracotomy are restricted in
      patients with associated chest trauma in presence of shock and acute blood loss.

PMID- 1385843
TI  - [Laparoscopy in penetrating wounds of the abdomen].
AB  - Within the recent 5 years, the authors observed 103 sufferers with penetrating
      injury to the abdomen. Operated on were 79 patients. Of them, 39 underwent
      explorative laparotomy. Laparoscopy was performed in obscure diagnosis in
      sufferers with associated trauma who were unconscious, in those with the signs of
      alcohol intoxication, in drug addicts etc. The advantages of the use of
      laparoscopy in the diagnosis, and in some patients--in the treatment of injuries
      were noted.

PMID- 1385845
TI  - [Programmed laparoenterostomy in incarcerated diaphragmatic hernia].

PMID- 1385846
TI  - Prophylactic antibiotic management of dental patients with prosthetic joints.

PMID- 1385847
TI  - [Laparoscopic hernia surgery has a future].

PMID- 1385848
TI  - [Predictive and prenatal diagnosis of Huntington's disease--ethical guidelines].

PMID- 1385850
TI  - [The prevalence of spondylopathies among the crane operators in the port of
      Venice].
AB  - A group of 78 crane operators were examined using the "EPM Research Unit" method
      for assessing spine function. Crane operators work in a fixed posture
      characterized by a flexed position of the cervical spine, isometric load of the
      extensor cervical muscles and increased dorsal kyphosis. The prevalence of spinal
      disorders was 39.7% for the cervical tract, 37.2% for the dorsal tract and 38.5%
      for the lumbar region. The results were compared with those concerning a control
      group. A statistically significant difference was found in the number of cervical
      and dorsal complaints (O.R. = 3.33 and 2.69), whereas the difference was nearly
      significant for the lumbar tract (O.R. = 1.65). The results suggest that this
      category of workers may be subject to an increased risk for the spine.

PMID- 1385851
TI  - New recommendations for immunization against pertussis and hepatitis B.

PMID- 1385849
TI  - Abnormal lipid and fatty acid compositions of kidneys from mice with polycystic
      kidney disease.
AB  - Renal cyst development in polycystic kidney disease (PKD) involves hyperplastic
      growth and extensive membrane alterations, suggesting abnormal membrane
      composition and function. Using thin-layer and gas-liquid chromatography, we
      analyzed the lipid components of the kidneys from 120-day-old DBA/2FG-pcy (pcy)
      having PKD as compared to normal DBA/2J (DBA) mice. At sacrifice, kidneys from
      pcy mice were four times larger than DBA controls, indicating that extensive
      renal cyst growth had occurred. The ratios of cholesterol/phospholipid, choline
      glycerophospholipid (GPC)/ethanolamine glycerophospholipid (GPE) and alkenylacyl
      GPE/diacyl GPE were higher (by 25%, 41% and 72%, respectively) in the cystic
      kidneys, while total phosphatidylinositol (PI), GPE and cardiolipin (DPG) were
      lower (by 13%, 23% and 27%, respectively). With respect to fatty acid
      compositions, there were significantly lower levels of docosahexaenoic acid (DHA,
      22:6n-3) and higher levels of adrenic acid (AdA, 22:4n-6) in the phospholipids of
      pcy mouse kidneys. These changes were not present in serum, indicating that they
      were not generalized differences. Interestingly, the lower level of DHA in GPE
      was found to be associated with the alkenylacyl, but not the diacyl species. The
      fatty acids comprising the product/substrate ratio for the delta 4 desaturase
      activity were lower across all phospholipids, indicating a possible abnormality
      in polyunsaturated fatty acid metabolism in this model of PKD. These lipid
      abnormalities may influence membrane-mediated events such as receptor activation,
      signal transduction, ion transport and enzyme activities. The renal
      pathophysiologies associated with PKD may be related to the tissue lipid
      abnormalities described herein.

PMID- 1385852
TI  - [Changes of hemodynamic parameters and urine output during laparoscopic
      cholecystectomy--compared with mini-laparotomy cholecystectomy: preliminary
      report].

PMID- 1385854
TI  - A dominant negative mutation in a spliceosomal ATPase affects ATP hydrolysis but
      not binding to the spliceosome.
AB  - PRP16 is an RNA-dependent ATPase required for the second catalytic step of
      splicing in vitro. A dominant suppressor of a branchpoint mutation in
      Saccharomyces cerevisiae, the prp16-1 allele, contains a Tyr to Asp change in the
      nucleotide-binding site consensus sequence. We now find that cells harboring the
      prp16-1 allele have a general growth defect that is exacerbated at cold
      temperatures. The mutant is dominant over the wild-type gene when overexpressed.
      Purified Prp16-1 protein binds to the spliceosome with apparently wild-type
      affinity; however, it only weakly complements the second-step block in a PRP16
      depleted extract. Analysis of purified Prp16-1 revealed that the rate of ATP
      hydrolysis is greatly reduced. These results can account for the dominant
      negative growth phenotype and argue that the ATPase activity of PRP16 is
      essential for its role in splicing. Moreover, since PRP16 is a member of the
      DEAD/H box families, these findings have important implications for a large class
      of proteins.

PMID- 1385853
TI  - Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1
      by the product of the RB1 gene.
AB  - The protein product of the retinoblastoma susceptibility gene, p110RB1, is a
      nuclear phosphoprotein [W.H. Lee, J.Y. Shew, F.D. Hong, T.W. Sery, L.A. Donoso,
      L.J. Young, R. Bookstein, and E.Y. Lee, Nature (London) 329:642-645, 1987] with
      properties of a cell cycle regulator (K. Buchkovich, L.A. Duffy, and E. Harlow,
      Cell 58:1097-1105, 1989; P.L. Chen, P. Scully, J.Y. Shew, J.Y. Wang, and W.H.
      Lee, Cell 58:1193-1198, 1989; J.A. DeCaprio, J.W. Ludlow, D. Lynch, Y. Furukawa,
      J. Griffin, H. Piwnica-Worms, C.M. Huang, and D.M. Livingston, Cell 58:1085-1095,
      1989; and K. Mihara, X.R. Cao, A. Yen, S. Chandler, B. Driscoll, A.L. Murphree,
      A. TAng, and Y.K. Fung, Science 246:1300-1303, 1989). Although the mechanism of
      action of p110RB1 remains unknown, several lines of evidence suggest that it
      plays a role in the regulation of transcription. We now show that overexpression
      of p110RB1 causes repression of the adenovirus early promoter EIIaE and the
      promoters of two cellular genes, c-myc and RB1, both of which contain E2F-binding
      motifs. Mutation of the E2 element in the c-myc promoter abolishes p110RB1
      repression. We also demonstrate that a p110RB1 mutant, which is refractory to
      cell cycle phosphorylation but intact in E1a/large T antigen-binding properties,
      represses EIIaE with 50- to 80-fold greater efficiency than wild-type p110RB1.
      These data provide evidence that hypophosphorylated p110RB1 actively represses
      expression of genes with promoters containing the E2F-binding motif (E2 element).

PMID- 1385855
TI  - Cellular biology of glomerulosclerosis.

PMID- 1385856
TI  - Gonadal-independent developmental changes in activation of N-methyl-D-aspartate
      receptors involved in gonadotropin-releasing hormone secretion.
AB  - Using hypothalamic explants of male rats, we have shown that the N-methyl-D
      aspartate (NMDA) receptors involved in a stimulatory control of gonadotropin
      releasing hormone (GnRH) secretion were transiently activated at 25 days around
      the time of onset of puberty. This was evidenced by studying the dose-related
      inhibition of veratridine-induced GnRH secretion by MK-801, a use dependent
      antagonist of NMDA receptors. An increase in sensitivity of GnRH secretion to the
      inhibitory effect of MK-801 was used as a marker of increased activation of NMDA
      receptors involved in stimulation of GnRH secretion. Here, we report on data
      obtained in intact and castrated rats at different ages. The aim was to determine
      whether the absence of gonads would affect the developmental changes in
      activation of NMDA receptors that we described recently. In pubertal (50-day-old)
      rats, orchidectomy resulted in an activation of NMDA receptors which was
      nonsignificant after 4 days but significant after 13 days. In prepubertal rats
      orchidectomized at 5 or 10 days and studied 10 days later, the NMDA receptors
      involved in GnRH secretion were also more activated than in intact animals. Using
      explants of intact and castrated animals, a similar increase in activation of
      NMDA receptors was observed between 15 and 25 days of age, a period preceding
      onset of puberty. Subsequently, between 25 and 50 days, a reduction in NMDA
      receptor activation was seen. This decrease was observed in intact rats showing
      normal sexual development and in castrated rats as well.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1385857
TI  - Antagonism of ceruletide, a cholecystokinin analog, to the neurochemical effects
      of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists,
      phencyclidine and MK-801, on regional dopaminergic neurons in the rat brain.
AB  - In the present study, we investigated the effects of ceruletide (CL), a
      cholecystokinin analog, on the neurochemical response to non-competitive N-methyl
      D-aspartate (NMDA) receptor antagonists, phencyclidine (PCP) and MK-801, of the
      dopaminergic neuron systems in the discrete regions of the rat brain.
      Systemically administered PCP (7.5 mg/kg, i.p.) or MK-801 (1.0 mg/kg, i.p.)
      produced significant increases in the tissue contents of dopamine metabolite,
      homovanillic acid (HVA), in the prefrontal cortex, the nucleus accumbens and the
      olfactory tubercle but not in the nucleus caudatus putamen after 60 min. The
      effects of NMDA receptor antagonists in the nucleus accumbens and the prefrontal
      cortex were partially antagonized by pretreatment with CL (80 and 400
      micrograms/kg, i.p., at 60 min prior to the drugs). While CL alone decreased the
      dopaminergic metabolism only in the nigrostriatal pathways in naive rats, the
      present results indicated that CL also attenuates the activities of the meso
      limbic and meso-cortical dopaminergic neuron systems when these are enhanced by
      either PCP or MK-801.

PMID- 1385858
TI  - [The surgical treatment of preperitoneal inguinal hernia: a comparison between
      the methods of Rives and Stoppa].
AB  - In groin hernia surgery pre-peritoneal prosthetic repair is a valid alternative
      to traditional inguinal repair in patients with a large area of transversalis
      fascia weakness: direct, inguinoscrotal, recurrent, bilateral hernias. Pre
      peritoneal prosthetic surgical approach by Rives' technique (little unilateral
      prosthesis) has been used in 121 cases (24% bilateral and 67% recurrent hernias)
      and by Stoppa's technique (great bilateral prosthesis) in 95 cases (26% bilateral
      and 55% recurrent hernias). The results demonstrated 9.9% morbidity and 5.7%
      recurrences by Rives' technique vs 3.1 morbidity and complete absence of
      recurrences by Stoppa's technique. These results confirm the validity of large
      prosthetic pre-peritoneal repair in groin surgery.

PMID- 1385860
TI  - Alzheimer's disease and the dental patient. Recognizing and dealing with
      dementia.

PMID- 1385859
TI  - [Congenital duodenal stenosis. A case treated in adulthood].
AB  - The authors report their experience the diagnosis and management of congenital
      duodenal malformation in adults. They emphasize problems and difficulties in this
      disease of pediatric age and the physiopathological adaptation in these years.
      They point out that surgery can modify important metabolic functions and sub
      clinical pathological conditions that the malformation made up.

PMID- 1385861
TI  - Modifications of cell cycle controlling nuclear proteins by transforming growth
      factor beta in the HaCaT keratinocyte cell line.

PMID- 1385862
TI  - Analysis of proteins binding to the proximal promoter region of the human
      cytomegalovirus IE-1/2 enhancer/promoter reveals both consensus and aberrant
      recognition sequences for transcription factors Sp1 and CREB.
AB  - Expression of the immediate early 1 and 2 gene (IE-1/2) of human cytomegalovirus,
      an important pathogen in immunosuppressed patients, is controlled by a strong
      enhancer/promoter. To define the promoter domain within this large cis-active
      region of about 550 nucleotides, DNA-protein interactions were studied. DNase I
      footprinting experiments using procaryotically expressed transcription factor Sp1
      revealed an extensive interaction of this transcription factor with both
      consensus and aberrant recognition elements within the IE-1/2 promoter region.
      Protection of these Sp1 binding sites could also be observed when nuclear
      extracts prepared from HeLa cells and permissive human fibroblast cells were
      used. After in vitro mutagenesis of Sp1 targets and transient expression of
      mutagenized CAT-expression plasmids, however, no significant reduction in CAT
      activities was found. By analyzing a series of 5' deletion mutants of the IE-1/2
      promoter region, a strong cis-acting element was localized between nucleotides 
      94 and -78, upstream of sites that interact with Sp1. Gel retardation experiments
      demonstrated binding of recombinant transcription factor CREB to this motif which
      reveals it as an aberrant CREB recognition sequence. Thus, this study identifies
      several previously unknown binding sites for transcription factors Sp1 and CREB
      within the proximal promoter region of the IE-1/2 gene, which differ markedly in
      their relevance for constitutive promoter function.

PMID- 1385863
TI  - Characterization of the factors binding to a PEPCK gene upstream hypersensitive
      site with LCR activity.
AB  - A previously described upstream hypersensitive site (HS) in the PEPCK gene at 
      4800 bp, termed HS A (1), has been characterized and determined to bind at least
      two factors. One of these is a member of the ubiquitous CREB/ATF family, and the
      second is a novel tissue specific protein, pep A. A construct carrying HS A and
      the PEPCK proximal promoter was tested in transgenic mice and its CAT activity
      compared to the proximal promoter alone. The HS A was shown to drive tissue
      specific, position-independent transcription of the CAT reporter gene 2-3 fold
      more effectively than the proximal promoter alone, with a concommitant 4-5 fold
      higher expression of CAT. Protein binding activity has been localized to a 33 bp
      region. This region contains a CRE (2) which is shown to bind a member of the
      CREB/ATF family through competition assays with an oligo containing a CRE from
      the proximal promoter and by the appearance of a supershift when the factor/oligo
      complex was exposed to CREB polyclonal antibody. Through restriction enzyme
      digests and competition of protein binding with an oligonucleotide homologous to
      HS A with a mutated CRE we have characterized a putative binding site for a liver
      specific factor. In vitro and 'in vivo' footprinting studies complement each
      other, as well as, mobility shift assay data in designating the binding site of
      the proteins. The CREB/ATF factor and Pep A bind independently of each other
      during short term incubations, however, both factors can be accomodated on the
      DNA substrate as a function of extended time of incubation. Preliminary
      biochemical analysis defines the subunit molecular mass of the CREB/ATF like
      proteins at 55, 42, and 35 kD, while the tissue specific material exists as a
      single homogeneous subunit polypeptide in SDS of molecular mass = 49 kD.

PMID- 1385864
TI  - Cloning, expression, and crystallization of recoverin, a calcium sensor in
      vision.
AB  - Recoverin, a recently discovered 23-kDa calcium-binding protein, activates
      retinal rod guanylate cyclase when the calcium level is lowered in the
      submicromolar range. We report here the cloning and sequencing of a cDNA for
      recoverin from a bovine retinal expression library. The recoverin coding sequence
      was inserted into a pET-11a expression vector under control of the T7 phage
      promoter. A second expression system, in which the coding sequence was placed
      under control of the lambda phage PR promoter, gave 10-fold higher yields (10 mg
      of purified recoverin per liter of Escherichia coli culture). The finding that
      retinal recoverin is myristoylated at its amino terminus led us to coexpress the
      recombinant protein and N-myristoyltransferase (EC 2.3.1.97). Myristoylated
      recombinant recoverin formed in this way in E. coli is like retinal recoverin in
      exhibiting a large calcium-induced shift in its tryptophan fluorescence emission
      spectrum. The availability of abundant protein enabled us to crystallize
      unmyristoylated recombinant recoverin and initiate x-ray studies. The space group
      of tetragonal crystals obtained from 75% saturation ammonium sulfate is I4 with
      unit cell dimensions a = 85.1 A and c = 59.8 A. These crystals of the calcium
      bound form of the protein diffracted to a resolution of 2.2 A. The expression
      systems described here open the door to high-resolution x-ray crystallographic
      and nuclear magnetic resonance studies of this new member of the EF-hand
      superfamily and to the elucidation of its precise mode of action as a calcium
      switch.

PMID- 1385866
TI  - Primary structures of chicken cone visual pigments: vertebrate rhodopsins have
      evolved out of cone visual pigments.
AB  - The chicken retina contains rhodopsin (a rod visual pigment) and four kinds of
      cone visual pigments. The primary structures of chicken red (iodopsin) and
      rhodopsin have been determined previously. Here we report isolation of three cDNA
      clones encoding additional pigments from a chicken retinal cDNA library. Based on
      the partial amino acid sequences of the purified chicken visual pigments together
      with their biochemical and spectral properties, we have identified these clones
      as encoding the chicken green, blue, and violet visual pigments. Chicken violet
      was very similar to human blue not only in absorption maximum (chicken violet,
      415 nm; human blue, 419 nm) but also in amino acid sequence (80.6% identical).
      Interestingly, chicken green was more similar (71-75.1%) than any other known
      cone pigment (42.0-53.7%) to vertebrate rhodopsins. The fourth additional cone
      pigment, chicken blue, had relatively low similarity (39.3-54.6%) in amino acid
      sequence to those of the other vertebrate visual pigments. A phylogenetic tree of
      vertebrate visual pigments constructed on the basis of amino acid identity
      indicated that an ancestral visual pigment evolved first into four groups (groups
      L, S, M1, and M2), each of which includes one of the chicken cone pigments, and
      that group Rh including vertebrate rhodopsins diverged from group M2 later. Thus,
      it is suggested that the gene for scotopic vision (rhodopsin) has evolved out of
      that for photopic vision (cone pigments). The divergence of rhodopsin from cone
      pigments was accompanied by an increase in negative net charge of the pigment.

PMID- 1385865
TI  - Changing patterns in cytoskeletal mRNA expression and protein synthesis during
      murine erythropoiesis in vivo.
AB  - The major cytoskeletal proteins alpha-spectrin, beta-spectrin, and ankyrin are
      synthesized and assembled into a supportive membrane skeleton during erythroid
      differentiation. Information on the temporal appearance of mRNA and protein
      species is essential for understanding both the cytoskeletal assembly process and
      the function of various isoforms. We have isolated highly enriched populations of
      fetal erythroid cells at various stages of maturation. mRNAs for erythroid
      ankyrin, alpha-spectrin, and beta-spectrin were expressed at all stages but there
      were differences in transcript types and levels. The ratio of 9-kilobase (kb) to
      7.5-kb erythroid ankyrin transcripts decreased markedly during differentiation,
      but there was no change in the ratio of the 10.1-kb and 9.3-kb erythroid beta
      spectrin transcripts. The relative amounts of ankyrin, alpha-spectrin, and beta
      spectrin mRNA increased during yolk sac cell differentiation, whereas only alpha
      spectrin mRNA increased during differentiation of the fetal liver cells. The
      amounts of beta-spectrin mRNA exceeded the amounts of alpha-spectrin mRNA in the
      early precursors from both yolk sac and fetal liver; protein synthetic levels
      showed the same pattern. The 16-day fetal peripheral reticulocytes, on the other
      hand, had the adult mRNA and protein synthetic ratios with alpha/beta greater
      than 1. The data indicate that at least two mechanisms exist to meet changing
      erythroid membrane cytoskeletal requirements during development in utero: (i)
      stage-specific processing of the mRNA for the major cytoskeletal linker protein
      ankyrin and (ii) developmentally regulated alpha/beta-spectrin protein synthetic
      rates.

PMID- 1385867
TI  - Antithrombotic effects of synthetic peptides targeting various functional domains
      of thrombin.
AB  - To determine in vivo functional roles for thrombin's structural domains, we have
      compared the relative antithrombotic and antihemostatic effects of (i) catalytic
      site antithrombin peptide, D-Phe-Pro-Arg; (ii) exosite antithrombin peptide, the
      C-terminal tyrosine-sulfated dodecapeptide of hirudin; and (iii) bifunctional
      antithrombin peptide, a 20-mer peptide combining catalytic-site antithrombin
      peptide and exosite antithrombin peptide with a polyglycyl linker. All three
      peptides inhibited thrombin-mediated platelet aggregation and fibrin formation in
      vitro. In vivo thrombus formation was measured in real time as 111In-labeled
      platelet deposition and 125I-labeled fibrin accumulation on thrombogenic segments
      incorporated into chronic exteriorized arteriovenous access shunts in baboons.
      Under low flow conditions, the continuous infusion of peptides reduced thrombus
      formation onto collagen-coated tubing by half at doses (ID50) and corresponding
      concentrations (IC50) of 800 nmol per kg per min and 400 nmol/ml for catalytic
      site antithrombin peptide, greater than 1250 nmol per kg per min and greater than
      1500 mumol/ml for exosite antithrombin peptide, and 50 nmol per kg per min and 25
      nmol/ml for bifunctional antithrombin peptide. Under arterial flow conditions,
      systemically administered bifunctional antithrombin peptide decreased thrombus
      formation in a dose-dependent manner for segments of collagen-coated tubing or
      prosthetic vascular graft ID50 and IC50 values of 120 nmol per kg per min and 15
      nmol/ml; this dose also produced intermediate inhibition of hemostatic function
      [bleeding time, 21 +/- 3 min vs. 4.5 +/- 0.5 min (baseline values); P less than
      0.001; activated partial thromboplastin time, 285 +/- 13 sec vs. 31 +/- 3 sec
      (baseline), P less than 0.001]. In contrast, thrombus formation onto segments of
      endarterectomized aorta was potently decreased by bifunctional antithrombin
      peptide with an ID50 value of 2.4 nmol per kg per min and an IC50 value of 0.75
      nmol/ml, a systemic dose that failed to affect hemostasis. Thus, inhibiting both
      thrombin's catalytic and exosite domains increases antithrombotic potency by
      several orders of magnitude over the inhibition of either domain alone,
      particularly at sites of deep arterial injury.

PMID- 1385868
TI  - Differential regulation of T helper phenotype development by interleukins 4 and
      10 in an alpha beta T-cell-receptor transgenic system.
AB  - To address the mechanisms controlling T helper (Th) phenotype development, we
      used DO10, a transgenic mouse line that expresses the alpha beta T-cell receptor
      from an ovalbumin-reactive T hybridoma, as a source of naive T cells that can be
      stimulated in vitro with ovalbumin peptide presented by defined antigen
      presenting cells (APCs). We have examined the role of cytokines and APCs in the
      regulation of Th phenotype development. Interleukin 4 (IL-4) directs development
      toward the Th2 phenotype, stimulating IL-4 and silencing IL-2 and interferon
      gamma production in developing T cells. Splenic APCs direct development toward
      the Th1 phenotype when endogenous IL-10 is neutralized with anti-IL-10 antibody.
      The splenic APCs mediating these effects are probably macrophages or dendritic
      cells and not B cells, since IL-10 is incapable of affecting Th phenotype
      development when the B-cell hybridoma TA3 is used as the APC. These results
      suggest that early regulation of IL-4 and IL-10 in a developing immune response
      and the identity of the initiating APCs are critical in determining the Th
      phenotype of the developing T cells.

PMID- 1385869
TI  - Phosphatidylinositol-glycan (PI-G)-anchored membrane proteins: requirement of ATP
      and GTP for translation-independent COOH-terminal processing.
AB  - Placental alkaline phosphatase (PLAP) belongs to a class of proteins that are
      anchored to the plasma membrane by a COOH-terminal phosphatidylinositol-glycan
      (PI-G) moiety. Nascent forms of such proteins undergo NH2- and COOH-terminal
      processing to yield the mature PI-G-tailed proteins. We previously introduced a
      shortened engineered form of preproPLAP (preprominiPLAP) that permits monitoring
      in cell-free preparations its sequential processing to the pro form and then to
      the mature PI-G-tailed form. Previous studies were carried out by synthesizing
      the preproprotein cotranslationally in the presence of rough microsomal membranes
      (RM). Because of the complexity of the cotranslational system it was not possible
      to determine whether cofactors were required for processing. We have now prepared
      RM that are preloaded with prominiPLAP but contain little mature PI-G-tailed
      miniPLAP. Maximal processing requires supplementation with both ATP and GTP.
      Inhibitors of PI-G biosynthesis do not affect processing. Since cleavage and PI-G
      addition are presumably catalyzed by a transamidase, the nucleoside triphosphate
      requirements suggest that there are additional steps in prominiPLAP processing
      prior to transamidation with PI-G. These may involve translocation of the pro
      protein in a proper conformational state to the transamidase site.

PMID- 1385870
TI  - Contraction characteristics and ATPase activity of skeletal muscle fibers in the
      presence of antibody to myosin subfragment 2.
AB  - To investigate the role of the myosin hinge region in muscle contraction, we
      examined the contraction characteristics and Mg-ATPase activity of glycerinated
      muscle fibers prepared from rabbit psoas in the presence and absence of
      polyclonal antibody directed against the subfragment 2 (S-2) region of myosin.
      The antibody-induced reduction of Ca(2+)-activated isometric force was always
      accompanied by a parallel decrease of muscle fiber stiffness, so that the
      stiffness versus force relation remained unchanged by the antibody treatment.
      Force-velocity relations of the fibers, obtained by applying ramp decreases in
      force at steady isometric forces, indicated that the antibody had no effect on
      maximum shortening velocity or on the shape of force-velocity curves.
      Simultaneous measurements of Mg-ATPase activity and Ca(2+)-activated force showed
      that Mg-ATPase activity of the fibers remained unchanged despite the antibody
      induced reduction of isometric force even to zero. These results indicate that
      when anti-S-2 antibody attaches to the S-2 region of myosin molecules, their
      heads still hydrolyze ATP but no longer contribute to both force generation and
      muscle fiber stiffness.

PMID- 1385871
TI  - Protein F, a fibronectin-binding protein, is an adhesin of the group A
      streptococcus Streptococcus pyogenes.
AB  - Binding to fibronectin has been suggested to play an important role in adherence
      of the group A streptococcus Streptococcus pyrogenes to host epithelial cells;
      however, the identity of the streptococcal fibronectin receptor has been elusive.
      Here we demonstrate that the fibronectin-binding property of S. pyogenes is
      mediated by protein F, a bacterial surface protein that binds fibronectin at high
      affinity. The gene encoding protein F (prtF) produced a functional fibronectin
      binding protein in Escherichia coli. Insertional mutagenesis of the cloned gene
      generated a mutation that resulted in the loss of fibronectin-binding activity.
      When this mutation was introduced into the S. pyrogenes chromosome by homologous
      recombination with the wild-type allele, the resulting strains no longer produced
      protein F and lost their ability to bind fibronectin. The mutation could be
      complemented by prtF introduced on a plasmid. Mutants lacking protein F had a
      much lower capacity to adhere to respiratory epithelial cells. These results
      demonstrate that protein F is an important adhesin of S. pyogenes.

PMID- 1385872
TI  - Sensitivity to vanadate and isoforms of subunits A and B distinguish the
      osteoclast proton pump from other vacuolar H+ ATPases.
AB  - Analysis of proton (H+) transport by inside-out vesicles derived from highly
      purified chicken osteoclast (OC) membranes has revealed the presence of a newly
      discovered type of vacuolar H+ ATPase (V-ATPase). Unlike vesicles derived from
      any other cell type or organelle, H+ transport in OC-derived vesicles is
      sensitive to V-ATPase inhibitors (N-ethylmaleimide and Bafilomycin A1) and
      vanadate (IC50, 100 microM), an inhibitor previously found to affect only P-type
      ATPases. The OC H+ ATPase contains several V-like subunits (115, 39, and 16 kDa)
      but subunits A and B of the catalytic domain of the enzyme differ from that of
      other V-ATPases. In OCs, subunit A has a mass of 63 kDa instead of the 67-70 kDa
      expressed in monocytes, macrophages, and kidney microsomes, which contain a
      vanadate-insensitive H+ ATPase. Moreover, two types of 57- to 60-kDa B subunits
      are also found: one is expressed predominantly in OCs and the other is expressed
      in kidney microsomes. The OC H+ pump may therefore constitute a class of H+
      ATPase with a unique pharmacology and specific isoforms of two subunits in the
      catalytic portion of the enzyme. This H+ ATPase is involved in resorption of bone
      and may be expressed in a cell-specific manner, thereby opening possibilities for
      therapeutic intervention.

PMID- 1385873
TI  - Development of [125I]RB104, a potent inhibitor of neutral endopeptidase 24.11,
      and its use in detecting nanogram quantities of the enzyme by "inhibitor gel
      electrophoresis".
AB  - Neutral endopeptidase 24.11, also known as the common acute lymphoblastic
      leukemia antigen, is a zinc metallopeptidase involved in the inactivation of
      biologically active peptides, such as the enkephalins and atrial natriuretic
      peptide. The highly potent radiolabeled inhibitor 2-((3-[125I]iodo-4
      hydroxy)phenylmethyl)-4-N-[3-(hydroxyamino-3-oxo-1- phenylmethyl)propyl]amino-4
      oxobutanoic acid ([125I]RB104; Ki = 30 pM) has been developed for the enzyme.
      [125I]RB104 is highly specific, its Ki for another widely distributed zinc
      peptidase, angiotensin-converting enzyme, being 15 microM. In binding studies
      using rat brain slices, [125I]RB104 was shown to have a high affinity (Kd = 300
      +/- 20 pM) and high specific binding at the Kd concentration (90%). With rat
      brain homogenates the Kd of [125I]RB104 was 26.8 +/- 0.9 pM, close to the
      kinetically derived Kd, 7.0 +/- 0.8 pM. Using the inhibitor, we have developed a
      simple, rapid, and quantitative technique to detect low nanogram quantities of
      the endopeptidase directly from tissue extracts after SDS/PAGE. The method has
      been used to show the presence of low quantities of the enzyme in rabbit bone
      marrow. Apart from its sensitivity, "inhibitor gel electrophoresis" using
      [125I]RB104 has the advantage over immunohistochemical methods of being able to
      label the enzyme in all tissues and species. It will therefore be of great value
      in determining the exact role of this important regulatory peptidase in a number
      of biological systems. Moreover, this one-step characterization of neutral
      endopeptidase 24.11 could be extended to other zinc metallopeptidases such as
      angiotensin-converting enzyme or collagenases, and inhibitors with affinities as
      high as RB104 could open the way to visualization of zinc metallopeptidases in
      different tissues by electron microscopy.

PMID- 1385874
TI  - T cells expressing variable elements of T-cell receptor beta 8 and beta 2 chain
      regulate murine IgE production.
AB  - After sensitization to ovalbumin (Ova) by inhalation of nebulized antigen, BALB/c
      mice respond with an early rise in IgE but not in IgG anti-Ova antibody
      production. Our purpose here was to analyze the repertoire of T cells that may
      contribute to regulating this IgE response. Initial study of Ova-reactive T-cell
      hybridomas showed that they selectively express the T-cell receptor variable beta
      chain (V beta) elements 2, 8.1/8.2, and 14. The frequency of T cells bearing
      these V beta elements in local draining lymph nodes of the airways and lungs
      (peribronchial-draining lymph nodes) after Ova inhalation was examined. Local
      sensitization increased the proportion of V beta 8.1/8.2 T cells in the
      peribronchial-draining lymph nodes, whereas expression of V beta 2 or V beta 14
      was similar in sensitized and nonsensitized animals. In the presence of increased
      antigen concentrations, V beta 8 and V beta 2 T cells were equally reactive to
      Ova when cell proliferation was assayed. Coculture of Ova-selected V beta 8 T
      cells from peribronchial-draining lymph nodes and spleens of sensitized animals
      with primed splenic B cells increased IgE but not IgG production. The V beta 8
      increase in IgE production was related to an increase in numbers of IgE-secreting
      B cells. In contrast, coculture of Ova-selected V beta 2 T cells with sensitized
      B cells had no stimulatory effect on either IgE or IgG production. Further,
      addition of V beta 2 cells to V beta 8 cells inhibited the V beta 8-induced
      augmentation of IgE production. These data indicate that T cells expressing
      different T cell receptors or, perhaps, different V beta elements may play
      different roles in IgE production in sensitized mice.

PMID- 1385875
TI  - N-methyl-D-aspartate receptor-mediated neuroprotection in cerebellar granule
      cells requires new RNA and protein synthesis.
AB  - Cerebellar granule cells are susceptible to the excitotoxin glutamate, which acts
      at N-methyl-D-aspartate (NMDA) receptors, as well as the neurotoxin 1-methyl-4
      phenylpyridinium ion (MPP+), the active cytotoxic metabolite of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP). Paradoxically, preincubation of cultured
      cerebellar granule cells with low concentrations of NMDA or glutamate markedly
      antagonizes the neurotoxicity resulting from subsequent exposure to toxic
      concentrations of either MPP+ or glutamate. The neuroprotective effects of NMDA
      and glutamate against MPP+ toxicity are observed at agonist concentrations as low
      as 1 microM, are blocked by specific NMDA receptor antagonists, and require at
      least 30 min to develop fully. Moreover, NMDA receptor-mediated neuroprotection
      is prevented by the RNA synthesis inhibitor actinomycin D or the protein
      synthesis inhibitor cycloheximide. Thus, in cerebellar granule cells activation
      of NMDA receptors by glutamate can result in either neurotoxicity or
      neuroprotection, depending on the apparent degree of receptor stimulation. NMDA
      receptor-mediated neuroprotection requires new RNA and protein synthesis and
      therefore appears to be mediated by the expression of a neuroprotective
      protein(s). These data demonstrate the presence of an active NMDA receptor
      mediated and transcriptionally directed neuroprotective mechanism in cerebellar
      granule cells.

PMID- 1385876
TI  - Intravesicular acidification correlates with binding of ADP-ribosylation factor
      to microsomal membranes.
AB  - The ADP-ribosylation factor (ARF), a highly conserved low molecular weight GTP
      binding protein, has been implicated to function in intracellular protein
      transport to and within the Golgi complex. In pancreatic acinar cells the ARF is
      confined to the cytoplasmic faces of trans-Golgi stack membranes, a compartment
      known to maintain a low intravesicular pH, which is established by a chloride
      dependent MgATP-driven proton pump. The present study shows that MgATP (2mM), but
      neither adenosine 5'-[gamma-thio]triphosphate in the presence of Mg2+ nor ATP in
      the absence of Mg2+, increases transfer of ARF from the surrounding medium into
      the vesicle membranes. The specific vacuolar-type proton pump inhibitor
      bafilomycin B1 (10 nM), the protonophore carbonylcyanide m-chlorophenylhydrazone
      (10 microM), and replacement of chloride in the incubation buffer by acetate or
      nitrate resulted in an almost complete inhibition of the MgATP-dependent
      association of ARF to the vesicle membranes. The results demonstrate that
      redistribution of ARF to the vesicle membrane correlates with the intravesicular
      pH established by a vacuolar-type H(+)-ATPase. The intravesicular pH appears to
      be one mechanism by which certain low molecular weight GTP-binding proteins
      become relocated from the cytosol to their specific membrane vesicles.

PMID- 1385877
TI  - Enhancement of rotational behavior induced by repeated administration of SKF38393
      in rats with unilateral nigrostriatal 6-OHDA lesions.
AB  - To clarify if the enhancement of rotational behavior induced by repeated
      administration of SKF38393 is mediated by upregulation of D1 and/or D2 receptors
      in the striatum, we investigated effects of SCH23390 and sulpiride on SKF38393
      induced rotational behavior and the changes in striatal dopamine receptors in
      rats with unilateral nigrostriatal 6-hydroxydopamine lesions (1). Repeated weekly
      administration of SKF38393 markedly enhanced the number of rotations and
      shortened the latency of rotational behavior depending on the number of SKF38393
      administrations 1 or 6 weeks after the treatment with 6-OHDA (2). A selective D1
      antagonist, SCH23390, but not a selective D2 antagonist, sulpiride, suppressed
      SKF38393-induced rotation and inhibited the enhancement by the repeated
      administration (3). Repeated administration of SKF38393 did not modify the
      density and the affinity of either the striatal D1 or D2 receptors in the
      striatum. These results suggest that the enhancement of SKF38393-induced
      rotational behavior by the repeated administration is not associated with the
      upregulation of striatal D1 and D2 receptors.

PMID- 1385878
TI  - Role of genotype in brain dopamine metabolism and dopamine-dependent behavior of
      mice.
AB  - In mice of eight inbred strains--BALB/c, AKR/J, DBA/2, CBA, C57B1/6, DD, CC57Br,
      and C3H/He--brain dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA), in striatum and nucleus accumbens with
      tuberculum olfactorium, the structures of two main dopaminergic systems-
      nigrostriatal and mesolimbic--were determined. In both dopaminergic regions, no
      strain effect on either dopamine or DOPAC levels was found, while for HVA content
      a highly significant hereditary determination was shown. Influences of selective
      D1 and D2 dopamine receptor agonists--SK&F 38393 and quinpirole, respectively--as
      well as that of a mixed D1/D2 agonist, apomorphine, on general locomotor activity
      and stereotypic climbing were studied. By that, marked genotypic differences in
      dopamine-dependent behavior and dopamine receptor sensitivity were observed.
      Although both SK&F 38393 (5 mg/kg) and apomorphine (0.25 mg/kg) decreased
      locomotion, the effect being genotype dependent, in all strains of mice
      quinpirole (2.5 mg/kg) proved more potent in locomotor inhibition. SK&F 38393 (10
      mg/kg) induced climbing, but 2.5 mg/kg apomorphine in most strains was much more
      effective. At the same time, quinpirole (up to 8 mg/kg) failed to induce this
      behavior. This suggests the crucial role of D1 receptors in the generation of
      climbing, attracting, at the same time, attention to the importance of D1/D2
      interaction. The observed drastic interstrain differences in dopamine receptor
      sensitivity demonstrate the essential role of genotype in the effects of
      dopaminergic drugs.

PMID- 1385879
TI  - Alterations of skin-associated lymphoid tissue in the carcinogenesis of arsenical
      skin cancer.
AB  - We investigated the skin-associated lymphoid tissue in arsenical skin cancers,
      including 14 Bowen's disease, 6 basal cell carcinoma and 6 squamous cell
      carcinoma patients from an endemic area by immunohistochemical and morphometric
      methods. There was a progressive decrease of Langerhans cells in the order of
      normal skin, normal appearing edge and arsenical cancers. A disruption of the
      uniform Langerhans cell dendrites was also noticed. The Langerhans cell density
      in arsenical tumors did not correlate with the peritumoral infiltrates. The
      prominent infiltrated cells in the peritumoral area had T cell markers. The
      number of peritumoral T lymphocytes in squamous cell carcinoma was significantly
      less than that of Bowen's disease and basal cell carcinoma. Peritumoral
      mononuclear infiltrates in Bowen's disease and squamous cell carcinoma showed a
      higher helper/suppressor T cell ratio than that in basal cell carcinoma. This may
      be accounted for by a selective increased recruitment of helper T cells to the
      tumor infiltrates in Bowen's disease and squamous cell carcinoma.

PMID- 1385880
TI  - [Primary infections of the thoraco-abdominal wall. Diagnostic imaging and
      interventional ultrasonography].

PMID- 1385881
TI  - [Chronic heart failure (X). Ventricular remodelling in myocardial infarct].

PMID- 1385882
TI  - [Lipomatous hypertrophy of the interauricular septum, fibrosis of the bundle of
      His and calcification of the mitral annulus associated with multiple rhythm and
      conduction disorders. The anatomicoclinical correlations].
AB  - We present the case of a 72 years old female with multiple episodes of atrial
      fibrillation, interatrial block and different degrees of atrioventricular block,
      that died because of stroke. Postmortem pathologic examination showed a
      lipomatous hypertrophy of the interatrial septum (previously suspected on
      echocardiogram), his bundle and right branch degeneration as well as mitral
      annular calcification extended to conduction system. According to these
      pathologic findings, rhythm and conduction disturbances are correlated with the
      two levels (atrial and atrioventricular) where anatomic abnormalities were found.

PMID- 1385883
TI  - Lack of evidence for central T-cell tolerance defects in lupus mice and for V
      beta-deleting endogenous superantigens in rats and humans.

PMID- 1385884
TI  - Do anergic T cells live or die?

PMID- 1385885
TI  - Redundant regulatory mechanisms as an outcome of evolutionary tinkering.

PMID- 1385886
TI  - [Liver, biliary tract (1). Cholecystectomy by laparotomy and surgical
      laparoscopy].

PMID- 1385887
TI  - [Laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy has been accepted clinically in a very short time.
      Following an intensive training-course for manual dexterity clinical experience
      should be achieved in carefully selected cases. After a certain number of
      cholecystectomies the majority of cholecystectomies can be performed
      laparoscopically. The complication rate of laparoscopic cholecystectomy in the
      hand of a well trained surgeon seams to be comparable or even smaller than in
      conventional procedure. The patients have significantly less pain and bodily
      activity starts early. The postoperative time in hospital in our clinic is two to
      three days. The rehabilitation-time could be shortened.

PMID- 1385888
TI  - [Hormonal assessment in a woman with acne and alopecia].
AB  - Acne, androgenogenetic alopecia, hyperseborrhea and hirsutism may result from
      hyperandrogenism in women. This may be peripheral "idiopathic" hyperandrogenism
      due to cutaneous metabolism of steroids, but in some cases hyperandrogenism is
      due to abnormal production or input of steroids with androgenic activity
      (hyperplasia, endocrine tumors, cysts, consumption of progestogens or other
      hormones with androgenic activity, menopause...). An assessment is useful only in
      cases of acne or alopecia if they are accompanied by other signs of peripheral
      hyperandrogenism and/or disturbed menstruation. The treatment is based on the
      administration of an anti-androgen (in France, usually cyproterone acetate),
      combined with other local or systemic treatments for the problem, depending on
      the age, dermatological signs and context.

PMID- 1385889
TI  - Permeability of protective gloves to (di)methacrylates in resinous dental
      materials.
AB  - Dentists may develop contact allergy induced by handling resinous dental
      materials, and vinyl and latex gloves may provide protection against the monomers
      of these materials only during the time it takes for a monomer to permeate the
      glove. The passage times and rates of penetration of four commonly used
      (di)methacrylates--HEMA, TEGDMA, BISGMA, and UEDMA--for 11 protective gloves were
      measured. The passage time for HEMA and TEGDMA through vinyl gloves was 1-3 min,
      and around 20 min for BISGMA and UEDMA. The rate of penetration of HEMA and
      TEGDMA in vinyl gloves was 0.5-4.5 mumol.min-1.cm-2. The passage time of HEMA and
      TEGDMA through most of the latex or the modified latex gloves was 5-8 min and the
      rate of penetration 0.5-3.1 mumol.min-1.cm-2. Latex or modified latex gloves
      provide a protection against BISGMA and UEDMA for 80 min or more with one
      exception (Elastyrene), which burst after about 50 min in contact with the
      resins. Of the tested gloves Ansell, Neutralon, Mediglove, and Biogel D provide
      protection against HEMA and TEGDMA for at least 5 min.

PMID- 1385890
TI  - Aspects on diagnosis and treatment of the foregut carcinoid syndrome.
AB  - Eight patients with the foregut carcinoid syndrome (two gastric and six bronchial
      primary tumors) are reported. The patients presented with complex clinical
      symptoms including ectopic production of adrenocorticotrophic hormone and growth
      hormone-releasing factors. The most alarming symptoms were facial flush and
      edema, accompanied by severe bronchoconstriction, which easily was misinterpreted
      as asthmatic attacks. Conventional bronchodilatory drugs may be potentially
      dangerous in these patients, in whom combined blockade of histamine receptors and
      treatment with cortisone and octreotide are recommended. Owing to the patients'
      age and general condition individualized long-term therapy was instituted.
      Surgical therapy under optimal protection by drugs can be of substantial value
      also in patients with advanced disease. One patient with life-threatening
      hormonal symptoms underwent hyperthermic perfusion of the liver with cytotoxic
      drugs, resulting in good palliation.

PMID- 1385891
TI  - Mutagenicity from ozonation of humic substances.
AB  - Eight structural components of humic substances were ozonated. Mutagenic activity
      was found using TA100 with and without S9 mix for all ozonated components. p
      Hydroxybenzaldehyde was chosen as an important component and ozonation products
      were determined by gas chromatography-mass spectrometry (GC-MS). Aldehydes,
      ketones and carboxylic acids were identified as the ozonation products. Among
      these products, acetaldehyde, formaldehyde, glyoxal, methylglyoxal and glyoxylic
      acid were recognized to be mutagenic. Furthermore, p-hydroxybenzaldehyde was
      first ozonated and then chlorinated. A great variety of chlorinated organic
      compounds, many of which are known mutagens, have been identified by GC-MS in the
      ether extract. The same compounds have previously been reported as chlorination
      products of humic substances. Aldehydic products by ozonation were identified
      from ozonation followed by chlorination of humic substances and p
      hydroxybenzaldehyde.

PMID- 1385893
TI  - [Evaluation of residents].

PMID- 1385892
TI  - Laparoscopic posterior truncal vagotomy and anterior highly selective vagotomy--a
      case report.
AB  - Laparoscopic vagotomy provides a viable alternative to expensive long-term
      treatment with H2 antagonists in patients with intractable peptic ulcer disease.
      The minimally invasive procedure offers reduced postoperative discomfort and
      improved cosmesis. Here, we report our first case of a posterior truncal vagotomy
      and anterior highly selective vagotomy performed laparoscopically for the first
      time in Asia. The surgery was uneventful. Diet was resumed on day 3 and the
      patient was discharged on day 4. Post-vagotomy acid secretion tests on the third
      week revealed a dramatic decrease in acid production. With further experience,
      laparoscopic vagotomy can be an attractive alternative to long term medication in
      peptic ulcer disease.

PMID- 1385894
TI  - [Dossier: health project in specialized halfway houses].

PMID- 1385895
TI  - [From the medical to the social: project of management of a unit for adult
      handicapped psychotics].

PMID- 1385896
TI  - [From the hospital unit to the specialized halfway house: new roles and new
      functions for the patient care team].

PMID- 1385897
TI  - Rectus abdominis hematoma after heparin injection.

PMID- 1385898
TI  - Childhood psychological trauma correlates with unsuccessful lumbar spine surgery.
AB  - In a retrospective study of 86 patients who underwent lumbar spine surgery,
      patients who had three or more of a possible five serious childhood psychological
      traumas (risk factors) had an 85% likelihood of an unsuccessful surgical outcome.
      Conversely, in patients with a poor surgical outcome, the incidence of these
      traumas was 75%. In the group of 19 patients with no risk factors, there was only
      a 5% incidence of failure. This study shows that a highly significant correlation
      exists between unsuccessful lumbar spine surgery and a history of childhood
      traumas. Although recognition of predictors for unsuccessful outcome can be
      useful in avoiding surgery in patients whose indications for surgery are
      borderline, the greater challenge is to help the patient who, despite being at
      high psychological risk for negative outcome, has severe spinal pathology that
      will likely require surgery. In such cases, psychiatric treatment is critical. In
      the group of 19 patients with no risk factors, single-level laminectomies and
      discectomies were performed on 6 patients. The other 13 cases were complex,
      involving a combination of repeat surgeries (n = 4) fusions (n = 3), and/or
      multilevel laminectomies and discectomies (n = 11).

PMID- 1385899
TI  - Intraosseous vertebral body pressures.
AB  - In an effort to determine the relationship between low-back pain and intraosseous
      hypertension, in vivo vertebral pressure measurements were performed on 19
      patients. A cannulated screw was placed percutaneously into the middle of the
      vertebral body by a transpedicular route. Pressure measurements were recorded
      with the patient in various positions. Pressures were greatest in the sitting
      position, lowest in the prone position, and intermediate in the standing
      position. A correlation was found between intravertebral body pressure and
      patient position. Pressures were highest in the positions most commonly
      associated with low-back pain.

PMID- 1385900
TI  - Pedicle diameter determined by computed tomography. Its relevance to pedicle
      screw fixation in the lumbar spine.
AB  - Intraoperative technical complications of pedicle screw fixation include screw
      cutout or maldirection and pedicle fracture. The aims of this study were 1) to
      use computed tomography to determine the average pedicle diameter; and 2) to
      compare these measurements with the outer diameter measurements of commonly used
      pedicle screws. The pedicle diameters of L2, L3, L4, L5, and S1 were measured in
      154 adult patients (81 men, 73 women) who had low-back pain. The distance across
      the isthmus of the pedicle was measured with the distance mode on the axial
      computed tomographic image in the bone window setting. The lateral computed
      tomographic scout view was used to select the axial section through the
      midportion of the pedicle. To standardize data retrieval, the lower four motion
      segments were denoted as L2-S1, even when there were more or fewer than five
      lumbar vertebrae. The pedicle diameter at each level was measured and averaged
      for all patients and for men and women separately. The percentage of pedicles
      that measured less than 7 mm was determined at each level. The average pedicle
      diameters were 8.13 mm for L2, 8.7 mm for L3, 10.88 mm for L4, 14.54 mm for L5,
      and 18.37 mm for S1. Twenty percent of the L2 pedicle diameters, 15.6% of L3, and
      1.9% of L4 were less than 7 mm; none of the L5 or S1 pedicles measured less than
      7 mm. The outer diameters of the most commonly used pedicle screws range from 5
      mm to 7 mm. Screw pitch, tooth profile, outer diameter, and depth of penetration
      affect implant strength.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385901
TI  - Which disc as visualized by magnetic resonance imaging is actually a source of
      pain? A correlation between magnetic resonance imaging and discography.
AB  - Sixty-three discs in 25 consecutive patients with nonradicular discogenic pain
      were studied with magnetic resonance imaging and lumbar discography. Sagittal T2
      magnetic resonance imaging sequences were blindly classified according to the
      nuclear signal intensity and to the status of the posterior anulus. A positive
      discogram had to include abnormal morphology and a provocative pain response of
      significant intensity and familiar quality. Specific magnetic resonance imaging
      patterns with a high probability for positive and negative discograms are
      identified. Also identified are magnetic resonance imaging patterns with
      intermediate probability, ie, ones that should not be presumed either
      asymptomatic or symptomatic. In many cases, magnetic resonance imaging could not
      reliably predict or replace discography.

PMID- 1385902
TI  - Intradiscal steroids. A prospective double-blind clinical trial.
AB  - A prospective, randomized, double-blind study was performed to evaluate the
      clinical efficacy of intradiscal steroid injections. Criteria for entrance were
      one-level internal disc disruption or nonsequestered nuclear prolapse with or
      without sciatica and a positive pain response on awake discography. Exclusion
      criteria were multilevel disease, central or lateral stenosis, prior lumbar
      surgery, or medical disease requiring systemic steroids. A total of 25 patients
      were randomly assigned to Treatment Group A (methylprednisolone, Depo-Medrol 80
      mg/ml, The Upjohn Co., Kalamazoo, Michigan) or Treatment Group B (bupivacaine,
      Marcaine .5% 1.5 ml, Sanofi Winthrop Pharmaceuticals, New York, New York).
      Fourteen patients received Depo-Medrol, with 21% showing subjective improvement
      and 79% no improvement; 0% were clinically worse. Eleven patients received
      intradiscal Marcaine, with 9% showing clinical improvement and 91% no
      improvement; 0% were clinically worse. To quantify clinical response, a pain
      diagram grid score, a visual analog scale, and the Oswestry Pain Questionnaire
      were used before injection and 10-14 days after injection. No statistically
      significant benefit was identified in the use of intradiscal steroids.

PMID- 1385904
TI  - [Surgical treatment of atypical location of a clavus on the lower extremity].
AB  - Clavus is a very frequent condition of the toes which, despite the fact that it
      is usually underrated, can complicate the life of its carriers. The authors
      describe a surgical technique tested in a group of 12 female patients in the
      course of six years, which became a simple method of choice for the elimination
      of these complaints.

PMID- 1385903
TI  - Effect of smoking and pulsed electromagnetic fields on intradiscal pH in rabbits.
AB  - The adverse effect of cigarette smoking on human spines has been noted
      indirectly. There is correlation of increased back pain among individuals who
      smoke heavily. The hypothesis of this study was that an environment of cigarette
      smoking is an adverse event and will create a reduced pH in the rabbit
      intervertebral disc. Electromagnetic fields, however, can defend against this
      adverse event and reduce the tendency toward acidic pH. Rabbits were exposed to
      cigarette smoke for 2, 4, or 6 weeks and their intradiscal pH measured. Cigarette
      smoke-exposed discs demonstrated a consistently lower pH than did the discs of
      the machine control rabbits. The second group of rabbits were exposed to
      cigarette smoke and pulsed electromagnetic fields. The cigarette-smoke-exposed
      rabbits that were exposed to the pulsed electromagnetic fields for 4 hr/day
      demonstrated no change in their intradiscal pH, in contrast to those who were
      exposed to smoke alone. In conclusion, cigarette smoke exposure in rabbits
      consistently produces a lower intradiscal pH and pulsed electromagnetic fields
      can defend against this adverse effect.

PMID- 1385905
TI  - You can treat the chemotherapy patient.
AB  - Increased numbers of cancer patients are treated with chemotherapy. Patients who
      receive antineoplastic agents can be at serious risk from dental infections and
      should be provided appropriate dental care. In many instances, indicated
      treatment can be accomplished by the patient's private dentist. Certain
      precautions, however, are necessary when treating dental patients medically
      compromised by chemotherapy. Dental conditions which may increase morbidity are
      identified and treatment recommendations are made. Guidelines for dental
      intervention before, during, and after chemotherapy are discussed with emphasis
      on the hematologic parameters necessary for safe dental care. The cyclic
      relationship between chemotherapy and oral complications is also reviewed.

PMID- 1385906
TI  - Reimbursement for the oral health care of cancer patients.
AB  - Oral conditions related to cancer therapy, which are largely preventable,
      continue to result in considerable morbidity, dysfunction and lost quality of
      life. Therefore, it is important for dentists to be knowledgeable about the
      problems of reimbursement for the oral health care of cancer patients and become
      involved in the issue of access to oral health care for cancer patients.

PMID- 1385907
TI  - Birth prevalence of Down syndrome in a predominantly Latino population: a 15-year
      study.
AB  - The birth prevalence of Down syndrome (DS), although decreasing in parts of the
      world, is not known in many specific subpopulations. The rate of DS for live
      births was determined for a 15-year period (1974-1988) at the Los Angeles County
      University of Southern California Medical Center, which is a large public
      hospital serving a predominantly Latino population. DS was ascertained primarily
      by clinical monitoring of newborn infants. The overall rate of DS was 1.60/1,000
      live births and had minimal fluctuation throughout the 15 years. The rate of DS
      for Latino births was 1.69/1,000 live births, 1.67 when adjusted for maternal
      age, and 1.75 when corrected for prenatal diagnosis. The high rate of DS in the
      Latino population was associated with advanced maternal ages and increased
      maternal-age specific rates for DS, especially in the age ranges of 30 to 34 and
      40 to 44 years, when compared with other studies.

PMID- 1385908
TI  - Modification of platelet function by isosorbide dinitrate in patients with
      coronary artery disease.
AB  - The effect of a four weeks oral treatment with 100 mg isosorbide dinitrate (ISDN)
      daily on platelet function was evaluated in 40 patients (aged 40-65 years) with
      proven coronary artery disease. Isosorbide dinitrate decreased platelet
      reactivity to ADP (p less than 0.001), increased platelet sensitivity to PGI2 (p
      less than 0.01) while the production of TXB2 from exogenous arachidonic acid
      substrate and from endogenous substrate were both significantly reduced.
      Circulating platelet aggregates as measured by the Wu-test were markedly reduced
      (p less than 0.001) but there was little change in the plasma concentration of
      the platelet proteins beta-thromboglobulin and platelet factor 4. Overall,
      platelet activation correlated with smoking, hypertension and a family history of
      coronary artery disease. The reduced platelet activation seen during treatment
      with isosorbide dinitrate may contribute to the therapeutic benefit seen with
      this drug in patients with coronary artery disease.

PMID- 1385910
TI  - Increased platelet activation in preterm labor.

PMID- 1385911
TI  - [Pelvic girdle relaxation and physiotherapy--prevention and treatment].

PMID- 1385909
TI  - Medium effects on the kinetics of human plasmin.
AB  - Effects of water-miscible organic solvents added to an aqueous buffer on the
      activity of several serine proteinases were studied. Plasmin in particular showed
      a dramatic difference in activity depending on the hydrophobicity of the added
      organic solvent through a combination of Km and kcat effects. An inverse linear
      correlation between the polarity of the mixed solvent and the log (kcat/Km) of
      plasmin activity was observed for both H-D-Val-Leu-Lys-p-nitroanilide (S-2251)
      and pro-urokinase as the substrate. The activity of plasmin was less dependent on
      the polarity of the added solvent when other chromogenic substrates were employed
      that contained an arginyl residue in the P1 site.

PMID- 1385912
TI  - [Down's syndrome. Medical care and rehabilitation].
AB  - The Norwegian Government has decided to reform the care of the mentally retarded
      by placing the responsibility for medical and social care with the local
      authorities. From 1 January 1991 the mentally retarded are to be integrated into
      the community. Persons with Down syndrome constitute 20-30% of the mentally
      retarded in institutions. The syndrome is the most common single cause of mental
      retardation. It represent both a medical challenge and a challenge in regard to
      home support, work, leisure activities and habilitation. Habilitation means
      identifying the fundamental deficiencies, incorporating this knowledge into plans
      for treatment and evaluating progress in social functioning and individual
      capacity. This presentation emphasizes clinically important information about the
      syndrome and medical complications both in the early stage of life, and among
      youths and adults in particular. Owing to difficulties in communication, there
      are often diagnostic problems. However, when recognized, many of the
      complications can be treated effectively.

PMID- 1385913
TI  - Changes in lymphocyte subsets and mitogen responsiveness following open-heart
      surgery and possible therapeutic approaches.
AB  - Septic multi-organ failure represents a common cause for operative mortality
      following open-heart surgery. One major reason might be the depression of cell
      mediated immunity. The purpose of this prospective randomized trial was to
      quantify and specify the effects of open-heart surgery on cell-mediated immune
      mechanisms. In addition, the immunorestorative potential of a combined
      immunomodulatory therapy with the cyclooxygenase inhibitor indomethacin and the
      thymomimetic substance Thymopentin versus single drug administration of
      indomethacin was investigated. Twenty patients were given indomethacin for the
      first 5 postoperative days (group A). Another 20 patients also received
      Thymopentin perioperatively and on the second and fourth postoperative days
      (group B), while 20 patients underwent conventional therapy (group C). Cell
      mediated immune response was quantified in vitro by measuring CD3+ T-lymphocytes
      and their subsets, CD4+ T-helper and CD8+ T-suppressor cells. Lymphocyte
      responsiveness to a specific (Antigen-Cocktail) and non-specific mitogen
      (phytohemagglutinin) provided information about the quality of cell-mediated
      immune response. On the first postoperative day CD3+ T-lymphocyte counts and
      Antigen-Cocktail-induced lymphocyte proliferation decreased significantly in all
      groups. The number of CD4+ T-Helper cells fell significantly only in groups A and
      C, while the decrease in group B was not statistically significant; the same
      applied to phytohemagglutinin-induced lymphocyte response. The CD4+/CD8+ ratio
      was significantly depressed only in group C, decreased slightly in group A and
      did not change as compared to baseline values in group B. All investigated
      parameters remained significantly depressed until the seventh postoperative day
      in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1385914
TI  - Induction of stable chimerism and transplantation tolerance to rat islet and
      heart allografts by ultraviolet-B modulation of bone marrow cells.
AB  - Ultraviolet-B irradiation (UV-B) (700 J/m2) of BM cells prior to transplantation
      into lethally gamma-irradiated (1050 rads) allogeneic rats prevents the
      development of GVHD and results in stable chimerism. This study was developed to
      determine if UV-B modulation of BMT is useful for preconditioning recipients for
      the induction of tolerance to donor islets and heart allografts. Lethally
      irradiated Lewis rats that received UV-B irradiated (700 J/m2) WF BMT (10(8) BM
      cells) demonstrated stable chimerism without any evidence of GVHD. The stable
      Lewis chimeras were made diabetic with streptozotocin (STZ) at 28-35 days after
      BMT and subdivided into 3 experimental groups that received 1000-1200 islets from
      WF, Lewis, or BN (third-party), respectively. The results showed that group I
      diabetic Lewis chimeras accepted permanently (greater than 300 days) BM donor WF
      islets and became normoglycemic. When 3 of 6 Lewis chimeras transplanted with WF
      islets were rechallenged with WF hearts 60 days after islet grafts, they accepted
      both islets and cardiac allografts permanently (greater than 240 days).
      Similarly, the remaining 3 animals accepted Lewis cardiac allografts permanently,
      thus indicating tolerance to both donor and recipient alloantigens. Group II
      diabetic chimeras accepted permanently (greater than 300 days) recipient (Lewis)
      islets. In contrast, group III chimeras rejected acutely (7-8 days) third-party
      (BN) islets. However, when these animals that rejected BN islets and again became
      diabetic were retransplanted with BM donor-type (WF) islets, they became
      permanently normoglycemic (greater than 200 days). This finding emphasizes the
      specificity of the induction of tolerance in this model and the apparent lack of
      organ-specific sensitization. To define the underlying mechanism of tolerance, in
      vivo adoptive transfer of 10(8) spleen cells to naive Lewis or WF recipients,
      obtained from tolerant Lewis chimeras carrying donor islets and heart allografts,
      showed no prolongation of cardiac allografts in the unmodified syngeneic hosts,
      thus questioning the role of suppressor mechanisms in the tolerant rats.
      Furthermore, cells from the tolerant chimeras that showed no mixed lymphocyte
      reaction (MLR) response to Lewis or; WF alloantigens failed to suppress anti
      Lewis and anti-WF MLR-response in coculture MLR. These results suggest that
      tolerance to donor alloantigens in the UV-B BMT model is most likely due to
      selective elimination of anti-BM donor helper or effector cell precursors (clonal
      deletion) rather than induction of suppressor cell activity. This study
      demonstrates that this relatively simple and effective approach to modulation of
      T cells in BM treatment may be potentially useful in the induction of tolerance
      to donor organs.

PMID- 1385915
TI  - [Postoperative duplex ultrasonic surveillance of infrainguinal arterial
      reconstructions].
AB  - Postoperative bypass surveillance can identify graft-related stenoses in 25% of
      grafts during the first two years after surgery. Correction of the stenoses
      before they lead to graft occlusion improves the patency significantly. Clinical
      assessment including distal pressure measurements is of poor sensitivity.
      Surveillance is best performed with color duplex scanning. Ideally, grafts are
      examined first after one to two months, thereafter every three months and, after
      one year, at intervals of six months. Graft surveillance beyond two years is
      hardly justified, as is the case with prosthetic grafts. Symptom-producing and
      tight stenoses should be corrected. Percutaneous transluminal angioplasty is
      appropriate for short stenoses, whereas stenoses longer than 2 to 3 cm are best
      treated surgically.

PMID- 1385916
TI  - Immune complex-mediated glomerulonephritis associated with bacterial kidney
      disease in the rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) developed a post-infectious chronic
      membranous glomerulonephritis 15 months after they had been experimentally
      infected with Renibacterium salmoninarum. Histologically, peritubular and
      periglomerular fibrosis, hypercellular glomeruli with occluded Bowman's space,
      and partial or complete adhesion to Bowman's capsule were constant features.
      Electron microscopy revealed thickened glomerular basement membranes with spikes
      accompanied by finely granular electron-dense deposits at the epithelial side and
      dense material in the mesangial matrix. Indirect immunofluorescence indicated
      linear immunoglobulin deposits along the glomerular basement membrane. The
      presence of R. salmoninarum was demonstrated by culture and by indirect
      immunofluorescence. Low serum hemagglutination-inhibiting antibody titers were
      demonstrated.

PMID- 1385917
TI  - [Drug clearance as a decision aid for further invasive liver diagnosis--studies
      with hexobarbital as a model substrate].
AB  - The clearance of a drug predominantly metabolized in the liver may serve as an
      estimate of quantitative liver function. In 260 consecutive patients presenting
      with a history of liver disease and abnormal laboratory findings but without a
      current definite diagnosis we have measured the clearance of hexobarbital and
      investigated if low values in patients are able to support the decision for an
      invasive diagnostic procedure such as needle biopsy or laparoscopy. 250 mg of
      hexobarbital was given orally to the patients between 8 and 10 hrs p.m. 12 hrs
      later blood samples were taken. Hexobarbital was determined by gas chromatography
      with N-selective detection, and a single point clearance was calculated. We
      recommended liver biopsy or laparoscopy to all patients with a hexobarbital
      clearance below 2.7 ml/min/kg body weight (normal 2.66-5.34 ml/min/kg). 73 out of
      260 patients showed a reduced hexobarbital clearance. In 44 patients blind liver
      biopsy (n = 14) or laparoscopy (n = 30) was performed, 29 patients refused an
      invasive diagnostic procedure. 17 out of 26 patients with the tentative diagnosis
      chronic hepatitis had already an incomplete or complete liver cirrhosis. In 11
      out of 18 patients with the tentative diagnosis alcohol toxic liver injury we
      found a progressive portal fibrosis or complete liver cirrhosis. Reduced drug
      clearance reflecting quantitative liver function can be an indicator of advanced
      liver disease, thus adding substantially to the decision for further invasive
      diagnostic procedures.

PMID- 1385918
TI  - Safety issues of latex products.

PMID- 1385919
TI  - Postoperative analgesia for major abdominal surgery with continuous thoracic
      epidural infusion of bupivacaine with sufentanil, versus bupivacaine with
      morphine. A randomized double blind study.
AB  - Forty-six patients undergoing major abdominal surgery were given postoperative
      epidural analgesia for four days with bupivacaine-sufentanil or bupivacaine
      morphine. Both groups received a bolus of 8 ml bupivacaine 0.5% followed after 30
      minutes by an infusion of 20 ml/h bupivacaine 0.1%. The sufentanil group (group
      A: 21 patients) received a loading dose of 50 micrograms sufentanil and a
      continuous infusion of 5 micrograms/h sufentanil. The morphine group (group B: 25
      patients) received no loading dose of morphine but only a continuous infusion of
      0.5 mg/h morphine. Both regimens provided excellent analgesia, but the frequency
      of respiratory depression was much greater in group A (33% versus 4% in group B).
      This respiratory depression occurred in the first hours postoperatively, when the
      patients were still in the post-anesthesia care unit. There was also a high
      incidence of hypotension after the loading dose of bupivacaine 0.5%. Although we
      noticed a large incidence of pruritus, no patient needed naloxone reversal. In
      view of these side effects we recommend a lower loading dose of both bupivacaine
      and sufentanil.

PMID- 1385920
TI  - Interactions between epidurally and intrathecally administered sufentanil and
      bupivacaine in hydroxypropyl-beta-cyclodextrin in the rat.
AB  - The interaction between inactive doses of the opioid sufentanil and the local
      anesthetic bupivacaine after complexation in various concentrations of
      hydroxypropyl-beta-cyclodextrin (HP-B-CD) were studied after epidural and
      intrathecal administration in the rat. Whereas 0.125 microgram sufentanil and 80
      micrograms bupivacaine produced only limited effects, a combination of the two
      compounds resulted in a profound surgical analgesia in all rats tested after
      epidural administration. Also intrathecally, a clear potentiation was present.
      The complexation of the same doses of sufentanil plus bupivacaine in HP-B-CD
      increased the duration of analgesia. Epidurally, a maximal potentiation of
      analgesia was present at 0.125 microgram sufentanil plus 80 micrograms
      bupivacaine in 20% HP-B-CD. Intrathecally, maximal potentiation of the analgesic
      activity was present starting from a complexation of both drugs in 10%
      hydroxypropyl-beta-cyclodextrin. Higher concentrations of hydroxypropyl-beta
      cyclodextrin did not significantly further increase the duration of analgesia.
      These results indicate that for both routes of spinal administration, the
      complexation of sufentanil plus bupivacaine in HP-B-CD can produce a longer
      analgesia than either plain sufentanil, sufentanil combined with bupivacaine or
      sufentanil alone in HP-B-CD. The complexation of sufentanil plus bupivacaine in
      HP-B-CD did not diminish the increased safety observed to occur after
      complexation of sufentanil in HP-B-CD and after combination of sufentanil plus
      bupivacaine.

PMID- 1385921
TI  - Surgical treatment of acute type V acromioclavicular injuries. A prospective
      study.
AB  - In a prospective study, 28 consecutive patients with an acute Type V
      acromioclavicular sprain were treated with a coraco-clavicular repair using a
      double velour Dacron graft. All patients were reviewed after a mean follow-up
      period of 5.1 years (range: 1 to 9 years). At follow-up, 20 patients (71.4%)
      showed good or excellent results, according to the Imatani evaluation system, and
      8 patients (28.6%) demonstrated a fair or poor result according to the same
      system. Loss of reduction was encountered in 11 shoulders (40%), despite an
      initial anatomical reduction. No correlation was seen between the overall scores
      at follow-up and the degree of residual dislocation, between the overall scores
      and the presence of coraco-clavicular calcifications or ossifications, between
      the overall scores and the development of posttraumatic arthritic changes, or
      between the overall scores and the presence of osteolysis of the distal clavicle.

PMID- 1385922
TI  - Sleep apnea syndrome in children--secondary to adenotonsillar hypertrophy?
AB  - In this study we investigated the relationship between the size of adenoids
      and/or tonsils and obstructive sleep apnea syndrome (OSAS) in 19 children aged 3
      to 7 years. After clinical examination by an ENT specialist, electrocardiogram
      (ECG), vectorcardiogram (VCG) and echocardiogram (EC) were performed while the
      patients were awake, and static charge sensitive bed (SCSB) method recording
      (noninvasive monitoring of ballistocardiogram, respiration and body movements)
      while asleep. After adenoidectomy and/or tonsillectomy, the volume of the tonsils
      and the adenoids was determined. RVH was found in 4 out of 19 children (21%). RVH
      findings correlated highly with the number of apneas but, surprisingly, not with
      measured adenotonsillar size in those children. However, at 6 months of follow
      up, the VCG and EC changes had returned to normal. These results suggest that RVH
      is more common in children suffering from upper airway obstruction than
      previously believed, and that factors other than adenotonsillar size also have an
      influence on upper airway obstruction.

PMID- 1385923
TI  - Receptor binding properties of the new and specific thromboxane receptor
      antagonist Bay U 3405.
AB  - Human platelet membranes were used to characterize the receptor binding
      properties of the specific thromboxane receptor antagonist 3H-SQ 29548 and the
      displacement of 3H-SQ 29548 from its binding site by the new thromboxane receptor
      antagonist Bay u 3405. The specific binding of 3H-SQ 29548 was saturable with an
      association rate constant of 1 x 10(-11) mol-1 min-1 and a dissociation rate
      constant of 0.032 min-1. Nonspecific binding of 3H-SQ 29548 was below 10%. When
      Scatchard plot analysis was performed on equilibrium saturation binding the kD
      was 69 nmol/l and the Bmax was calculated as 3.9 pmol/mg membrane protein. 3H-SQ
      29548 was dose dependently displaced from its binding site by addition of
      increasing concentrations of Bay u 3405 yielding an IC50 value of 68 +/- 12
      nmol/l, being not significantly different from the IC50 of nonlabelled SQ 29548
      (38 +/- 13 nmol/l). The results show that Bay u 3405 is a potent and specific
      thromboxane receptor antagonist, displacing 3H-SQ 29548 from its binding site on
      human platelet membranes with IC50 values being not significantly different.
      These receptor binding properties and the long biological half life reported in
      vivo make Bay u 3405 a promissing compound for the treatment of human
      cardiovascular diseases.

PMID- 1385924
TI  - pH-dependent binding of the TXA2/PGH2-receptor of human platelet membranes to
      various ligands.
AB  - [3H]-BAY U 3405 was used to characterize the pH-dependency of the binding of
      various ligands to the TXA2/PGH2-receptor of human platelet membranes. Maximum
      binding of [3H]-BAY U 3405 is achieved at pH 5.8. In inhibition studies the
      ligands Daltroban, CTA2, and U 46619 also show a higher affinity at pH 5.8
      compared to pH 7.4. In contrast, the ligands I-PTA-OH and GR 32191 have a higher
      affinity at pH 7.4. No difference is seen with SQ 29548. The ligands I-PTA-OH, GR
      32191, and SQ 29548 have a second protonable group in common, which is thought to
      be the reason for the different pH-dependent binding.

PMID- 1385925
TI  - Concomitant aspirin treatment abolishes the antiatherosclerotic effects of the
      calcium channel blocker isradipine mediated by PGI2.
AB  - 108 male rabbits, aged 6 months, with experimental hypercholesterolemia and
      experimental abdominal aortic lesioning received different regimen of
      antiatherosclerotic treatment; 36 of them were treated with isradipine, a
      dihydropyridine calcium antagonist (0.3 mg/kg/daily), 36 with isradipine in
      combination with aspirin whereas 36 animals received placebo. The entry of 125I
      radiolabelled LDL into the aorta was demonstrated to be significantly diminished
      in isradipine-treated rabbits as well as positive Sudan-III-staining and aortic
      cholesterol content were in comparison to placebo. This benefit was almost
      completely abolished by concomitant aspirin-treatment. The notable increase in
      vascular prostacyclin (PGI2) is supposed to mediate the strong
      antiatherosclerotic effect of isradipine resulting in an inhibition of LDL-entry
      and vascular cholesterol accumulation. Aspirin almost totally blocked the raise
      in PGI2-synthesis by the inhibition of cyclooxygenase detected in isradipine
      treated animals. It can be concluded, that aspirin-treatment may minimize the
      antiatherosclerotic actions of calcium antagonists which are mediated by the PG
      system.

PMID- 1385926
TI  - Real-time three-dimensional reconstruction of intravascular ultrasound images of
      iliac arteries.

PMID- 1385927
TI  - Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall
      remodeling in anemia-induced cardiac hypertrophy in rats.
AB  - To determine the effects of chronic anemia on the functional and structural
      characteristics of the heart, 1-month-old male rats were fed a diet deficient in
      iron and copper, which led to a hemoglobin concentration of 4.63 g/dl, for 8
      weeks. At sacrifice, under fentanyl citrate and droperidol anesthesia, systolic,
      diastolic, and mean arterial blood pressures were decreased, whereas differential
      pressure was increased. Left ventricular systolic pressure and the ventricular
      rate of pressure rise (mmHg/s) were reduced by 9% and 14%, respectively.
      Moreover, developed peak systolic ventricular pressure and maximal dP/dt
      diminished 14% and 12%. After perfusion fixation of the coronary vasculature and
      the myocardium, at a left ventricular intracavitary pressure equal to the in vivo
      measured end diastolic pressure, a 10% thickening of the left ventricular wall
      was measured in association with a 13% increase in the equatorial cavitary
      diameter and a 44% augmentation in ventricular mass. The 52% hypertrophy of the
      right ventricle was characterized by an 11% thicker wall and a 37% larger
      ventricular area. The 33% expansion in the aggregate myocyte volume of the left
      ventricle was found to be due to a 14% myocyte cellular hypertrophy and a 17%
      myocyte cellular hyperplasia. These cellular parameters were calculated from the
      estimation of the number of myocyte nuclei per unit volume of myocardium in situ
      and the evaluation of the distribution of nuclei per cell in enzymatically
      dissociated myocytes. Myocyte cellular hyperplasia provoked a 9% increase in the
      absolute number of cells across the left ventricular wall. In contrast, myocyte
      cellular hypertrophy (42%) was responsible for the increase in myocyte volume of
      the right ventricle. The proliferative response of left ventricular myocytes was
      not capable of restoring diastolic cell stress, which was enhanced by the changes
      in ventricular anatomy with anemia. In conclusion, chronic anemia induced an
      unbalanced load on the left ventricle, which evoked a hyperplastic reaction of
      preexisting myocytes, in an attempt to normalize diastolic wall and myocyte
      stress.

PMID- 1385928
TI  - Endotoxin-induced cytokine gene expression in vivo. IV. Expression of interleukin
      1 alpha/beta and interleukin-1 receptor antagonist mRNA during endotoxemia and
      during endotoxin-initiated local acute inflammation.
AB  - After the intravenous (IV) injection of endotoxin, (lipopolysaccharide [LPS]), in
      the rat, interleukin-1 alpha/beta (IL-1 alpha/beta) mRNA expression peaks at 1
      hour in whole organ RNA preparations of the lung, liver, spleen, and bowel.
      Interleukin-1 receptor antagonist (IL-1ra) mRNA peaks at 2 to 4 hours, consistent
      with the hypothesis that IL-1ra acts as an endogenous negative feedback mechanism
      to downregulate the proinflammatory effects of IL-1. After the intratracheal (IT)
      injection of LPS, however, IL-1 and IL-1ra mRNA levels in whole lung peak at 6
      hours, concurrent with the maximum influx of neutrophils (PMNs) into the
      bronchoalveolar space. To address the cellular source of IL-1 and IL-1ra mRNA in
      the lung during acute pneumonitis, mRNA levels were studied in bronchoalveolar
      lavage (BAL) macrophages incubated with LPS in vitro for 6 hours as compared with
      BAL cells (95% PMNs) obtained 6 hours after IT injection of LPS. A much greater
      expression of IL-1 and IL-1ra mRNA was observed in PMN-rich BAL cells obtained
      after IT injection of LPS, suggesting that PMNs contribute substantially to IL-1
      and IL-1ra mRNA expression. Fractionation of alveolar macrophage-enriched and PMN
      enriched subpopulations from the BAL cells obtained at 6 hours after IT injection
      of LPS confirmed that neutrophils are a source of IL-1 and IL-1ra mRNA. The
      difference in the kinetics of IL-1 and IL-1ra mRNA expression in whole lung RNA
      preparations after IV and IT injections of LPS is due to the contribution of PMNs
      that appear in the lung in large numbers after IT injection. Finally, human
      peripheral blood PMNs were found to express IL-1ra mRNA and protein after in
      vitro incubation with LPS. PMNs may contribute to the up- and downregulation of
      their own accumulation by expressing both IL-1 and IL-1ra.

PMID- 1385929
TI  - Comparison of the effects of loratadine and astemizole in the treatment of
      children with seasonal allergic rhinoconjunctivitis.
AB  - The efficacy and safety of a once-daily dose of loratadine 10 mg (5 mg in
      patients whose body weight was less than or equal to 30 kg) and astemizole 2
      mg/10 kg body weight o.d. were compared in a 14-day third-party blind study.
      Forty-one children (30 boys and 11 girls, aged 6-14 years) with seasonal allergic
      rhinoconjunctivitis entered the study. The pollen count was monitored throughout
      the study. A significant improvement (p less than 0.01) in allergy symptoms was
      observed from the third day for both drugs; there was no significant difference
      between drugs, although loratadine led to a greater reduction in symptoms. In the
      astemizole group, the apparently rapid onset of drug action might by explained by
      reduced pollen exposure. Therapeutic response was excellent/good in 83.3% and
      58.8% of the loratadine and astemizole groups, respectively. The results reported
      by the patients/parents were similar. Nine of the children on astemizole and four
      children on loratadine complained of side effects; three patients in the
      astemizole group were withdrawn from treatment because of adverse effects. No
      abnormal changes in lab values were observed in either group.

PMID- 1385930
TI  - Increasing the activity of affinity-purified DNA-binding proteins by adding high
      concentrations of nonspecific proteins.
AB  - A large decrease in the activity of two sequence-specific DNA-binding proteins
      implicated in transcription control was seen when these were affinity purified
      and assayed under standard conditions in electrophoretic mobility shift assays.
      Increasing the concentration of bovine serum albumin in the reaction mixtures
      from 0.1 to 5 mg/ml stimulated the DNA-binding activity of these affinity
      purified proteins, human CREB (cyclic AMP response element binding protein) and
      MDBP (methylated DNA-binding protein), approximately 5-to more than 20-fold. In
      the case of affinity-purified MDBP, adding back the affinity flow-through
      fraction to the assay mixture gave similar extents of stimulation at much lower
      final protein concentrations. The specific DNA-binding activity of the affinity
      purified CREB, but not that of MDBP, was also increased by adding a nonionic
      detergent to the binding reaction buffer although not as much. The large increase
      in the amount of MDBP.DNA complex seen upon supplementation of the affinity
      purified MDBP with the affinity flow-through fraction or 5 mg/ml of BSA was shown
      to be due to stimulation, by nonspecific proteins, of specific complex formation
      and not to prevention of activity losses by adsorption or denaturation during the
      assay.

PMID- 1385931
TI  - Effects of hypocarbia on the pharmacodynamics of sufentanil in humans.
AB  - Descriptors of power and frequency derived from power spectral analysis of the
      electroencephalogram (EEG) were used to determine the effects of low-dose
      sufentanil (0.1 micrograms/kg) on brain activity. The effects of hypocarbia alone
      and of hypocarbia with sufentanil in patients receiving a N2/O2 (70%:30%)
      anesthetic were also studied. Hypocarbia alone caused changes in most EEG
      descriptors from both the anterior (F3-C3) and posterior (P3-O1) EEG montages.
      All EEG descriptors in both hypocarbic and normocarbic patients significantly
      changed when sufentanil was administered, reflecting a shift of power into the
      lower frequency ranges. When the anterior EEG montages from the two groups that
      received sufentanil were compared, the delta power band, spectral edge 50 (median
      power frequency), and the relative power in the delta power band divided by the
      alpha plus beta power bands [D/(A + B)] in the hypocarbic group exhibited a
      significantly greater shift of power into the lower frequency range. It is
      concluded that (a) power spectral analysis is a sensitive measure of the effects
      of hypocarbia and small doses of sufentanil on the brain; (b) the power spectral
      analysis descriptors--delta power band, spectral edge 50, and [D/(A + B)]--are
      statistically the most sensitive to EEG changes induced by sufentanil; and (c)
      hypocarbia intensifies patient EEG response to sufentanil, as judged by changes
      in EEG descriptors.

PMID- 1385933
TI  - NMDA receptor complex antagonists have ethanol-like discriminative stimulus
      effects.

PMID- 1385932
TI  - Cannabinoid receptor localization in brain: relationship to motor and reward
      systems.

PMID- 1385934
TI  - Effects of cocaine on evoked field potentials in the rat striatum.

PMID- 1385935
TI  - Role of dopamine receptors in the nucleus accumbens in the rewarding properties
      of cocaine.

PMID- 1385936
TI  - Cocaine administration: D1 dopamine receptor function and dopamine
      clearance/diffusion in rat striatum and nucleus accumbens.

PMID- 1385937
TI  - Electrophysiological correlates of psychomotor stimulant-induced sensitization.

PMID- 1385938
TI  - Ionic modulation of the effects of heparin on plasminogen activation by tissue
      plasminogen activator: the effects of ionic strength, divalent cations, and
      chloride.
AB  - Ionic strength, divalent cations, and Cl- modulate the ability of the
      glycosaminoglycan heparin to stimulate the activation of human plasminogen (Pg)
      by tissue-type Pg activator. Kinetic analysis of Pg activation indicates that
      heparin is inhibitory, stimulatory, or nonstimulatory as a function of ionic
      strength. While increasing ionic strength inhibits Pg activation in the absence
      of heparin, in it presence an activation phase followed by an inhibitory phase is
      observed. Divalent cations, inhibitors of activation in the absence of heparin,
      increase the rate of activation in its presence. Kinetic analysis demonstrates
      that divalent cations augment the heparin stimulatory effect a maximum of 60-fold
      due to increases in kcat without changes in Km of the reaction. This effect is
      heparin-specific, since activation is not affected by Ca2+ in the presence of
      heparan sulfate or de-N-sulfated heparin. Also, Cl- inhibits Pg activation in the
      presence of heparin by acting as a competitive inhibitor (Kic of 100 mM).
      Furthermore, inhibition by Cl- reduces the overall magnitude of heparin
      stimulation of Pg activation. These results suggest that physiologic ions in
      combination with heparin may be significant effectors of Pg activation in the
      vascular microenvironment.

PMID- 1385939
TI  - Coupled expression of Ca2+ transport ATPase and a dihydrofolate reductase
      selectable marker in a mammalian cell system.
AB  - Stable expression of a full-length cDNA encoding chicken fast muscle Ca2+
      transport ATPase was obtained in a Chinese hamster lung cell line (DC-3F), using
      a dual-promoter expression vector (pH beta FCaA3) in which the ATPase was cloned
      downstream of a human beta-actin gene promoter, and a mutant dihydrofolate
      reductase cDNA (A3/DHFR) was cloned downstream of an SV40 promoter-enhancer.
      Owing to its essentially normal catalytic activity and modest (20-fold)
      resistance to the antifolate methotrexate (MTX), the A3/DHFR mutant enzyme served
      as an efficient dominant selection marker in transfected cell populations
      challenged with MTX and, within a broad range of drug concentrations, allowed
      subsequent amplification and overexpression of vector sequences. In stable
      transfectants, the expressed ATPase was targeted to intracellular membranes, and
      the microsomal fractions from those cells exhibited high rates of Ca2+ transport.
      In comparative experiments using transient expression in COS1 cells, the level of
      ATPase per transfected cell was greater, but less than 5% of the transfected
      population exhibited ATPase expression. Furthermore, as opposed to the stable
      lines, the transiently expressing cells could not be propagated. Overall, the
      yield of ATPase was 12-16 and 4-6 micrograms per milligram of microsomal protein
      in the stable and the transient expression systems, respectively. The advantages
      of the stably transfected cell lines therefore lie in the homogeneity of ATPase
      expression and its distribution in cells and microsomes, in the large yield of
      microsomes obtained by continuous cell propagation, and in the reproducible
      functional characteristics of the microsomes. Moreover, the microsomes derived
      from stably transfected cell lines provide a convenient system for studies of
      Ca2+ transport and ATPase partial reaction, eliminating the need to conduct
      repetitive transient transfections to obtain sufficient amounts of enzyme for
      functional studies.

PMID- 1385940
TI  - Effect of education, occupation and some lifestyle factors on common rheumatic
      complaints in a Swedish group aged 50-70 years.
AB  - The relation between common rheumatic diseases such as osteoarthrosis, arthralgia
      without definite signs of osteoarthrosis, subacromial shoulder pain, different
      forms of tendinitis, low back pain and neck pain, and the level of formal
      education, occupational workload and some lifestyle factors were examined in 502
      of 900 randomly selected subjects aged 50-70 years. The group with rheumatic
      complaints had a higher proportion of subjects with a lower level of formal
      education (less than or equal to eight years) by bivariate analysis. In
      multivariate analysis, the major risk factors were: a self rated heavy workload
      (odds ratio (OR) 6.4), sleep disturbance (OR 3.6), and advanced age (OR 2.0 per
      five year increase) for osteoarthrosis; a self rated heavy workload for
      subacromial shoulder pain (OR 5.4) and low back pain (OR 4.8); and a self rated
      heavy workload (OR 8.0) and female sex (OR 4.8) for neck pain. A self rated heavy
      workload was strongly correlated with a low level of formal education. A heavy
      workload (i.e. previous or present principal occupation) could only be confirmed
      in the groups with neck pain and low back pain on the basis of available
      occupational classification data. Neck pain was thus associated with occupations
      entailing repetitive tasks and awkward posture with respect to the neck,
      shoulders, and back. Low back pain was associated with occupations entailing
      awkward posture with respect to the neck, shoulders, and back, and occupations
      entailing exposure to vibration and heavy manual work. It is concluded that, in a
      cross sectional sample of an elderly population, a low level of formal education
      and self rated heavy physical work are associated with the occurrence of adult
      rheumatic complaints, though the self rated heavy workload could only be verified
      in the groups with neck pain and low back pain. There correlations between heavy
      work and low back pain, and especially neck pain, suggest that successful
      prevention would mean a substantial economic gain to the community. Whether the
      level of education is a marker of risk factors other than a heavy occupational
      workload needs further evaluation.

PMID- 1385941
TI  - Pityriasis rosea and discoid eczema: dose related reactions to treatment with
      gold.
AB  - Sixteen cases of either a pityriasiform or discoid eczematous rash occurring in
      patients with rheumatoid arthritis receiving treatment with gold (sodium
      aurothiomalate and auranofin) were studied. The results suggest that this is a
      dose related, not allergic, reaction to gold. The development of this rash is not
      an absolute indication to stop treatment with gold. Control can often be effected
      with potent topical steroids or a reduction in the dose or frequency of treatment
      with gold.

PMID- 1385942
TI  - Laparoscopic appendectomy. Initial experience in a teaching program.
AB  - From February 1990 to December 1991, 16 laparoscopic procedures were performed
      for right lower quadrant pain. There were nine men and seven women, aged 16 to 47
      years (mean, 27.2 years). All procedures were performed by surgical chief
      residents with prior experience in laparoscopic cholecystectomy, first-assisted
      by an attending surgeon. The appendix was visualized and a definitive diagnosis
      was made in all patients. One patient with acute salpingitis underwent diagnostic
      laparoscopy only; two patients underwent laparotomy (perforated appendicitis,
      perforated diverticulitis). A fourth patient had an acute torsion of an ovarian
      cyst managed laparoscopically. Laparoscopic appendectomy was successfully
      performed in 12 patients (acute appendicitis, 9; fibrosis or chronic
      inflammation, 2; normal appendix, 1). Mean operative time for laparoscopic
      appendectomy was 95.7 minutes, and mean postoperative stay was 2.5 days. The
      authors conclude that operative time, diagnostic accuracy, and complication rates
      for laparoscopic appendectomy are acceptable. Within the context of a training
      program, laparoscopic appendectomy provides an opportunity for surgical residents
      to expand laparoscopic skills.

PMID- 1385943
TI  - Selective cholangiography. Current role in laparoscopic cholecystectomy.
AB  - The initial 22-month experience with laparoscopic cholecystectomy in 400 patients
      employing an algorithm of selective cholangiographic evaluation is reported.
      Preoperative or postoperative endoscopic retrograde cholangiography was performed
      whenever stones were suspected clinically. Preoperative endoscopic retrograde
      cholangiography was performed in 44 patients (11%), in whom 14 (3.5%) had an
      endoscopic sphincterotomy with extraction of common bile duct stones.
      Intraoperative cholangiography was performed in only eight patients (2%) almost
      exclusively to acquire experience with the technique, and all cholangiograms were
      normal. Laparoscopic cholecystectomy was successfully completed in 96% of the
      patients. There were no deaths in this series, and major complications occurred
      in only 5% of patients. Two patients (0.5%) had a significant common bile duct
      injury that was recognized and successfully repaired at the initial operation. No
      late common bile duct strictures have been recognized. Six patients (1.5%)
      underwent postoperative endoscopic retrograde cholangiography for suspected
      common bile duct stones, with three patients requiring endoscopic sphincterotomy
      and stone extraction. This experience suggests that the use of preoperative and
      postoperative endoscopic retrograde cholangiography can be based on clinical
      presentation and laboratory evaluation and does not need to be performed
      routinely. Routine intraoperative cholangiography is not necessary in most
      patients undergoing laparoscopic cholecystectomy. The authors conclude that
      laparoscopic cholecystectomy can be performed safely with the selective use of
      cholangiography.

PMID- 1385945
TI  - The sarcoplasmic reticulum Ca(2+)-ATPase, SERCA1a, contains endoplasmic reticulum
      targeting information.
AB  - The fast-twitch skeletal muscle Ca(2+)-ATPase isoenzyme, SERCA1a, is localized in
      chick skeletal myotubes to both the sarcoplasmic reticulum (SR) and to the
      nuclear envelope, an extension of the endoplasmic reticulum (ER). The ER labeling
      remained after cycloheximide treatment, indicating that it did not represent
      newly synthesized SERCA1a in transit to the SR. Expression of the cDNA encoding
      SERCA1a in cultured non-muscle cells led to the localization of the enzyme in the
      ER, as indicated by organelle morphology and the co-localization of SERCA1a with
      the endogenous ER luminal protein, BiP. Immunopurification analysis showed that
      SERCA1a was not bound to BiP, nor was any degradation apparent. Thus, the SR
      Ca(2+)-ATPase appears to contain ER targeting information.

PMID- 1385946
TI  - The human complement C4B/steroid 21-hydroxylase (CYP21) and complement C4A/21
      hydroxylase pseudogene (CYP21P) intergenic sequences: comparison and
      identification of possible regulatory elements.
AB  - We determined the 1.8 kb intergenic sequences between the human complement C4B
      gene and the active steroid 21-hydroxylase gene in two subjects, and between the
      C4A gene and the steroid 21-hydroxylase pseudogene in one subject. Comparison of
      these sequences with each other and with published homologues revealed no
      differences which were unique to either intergenic region. Sequence analysis
      revealed two copies of an AGGTCA motif in all sequences. This motif is common to
      steroidogenic enzyme gene promoters and to the response elements for nuclear
      hormone receptors. Similarities with human enhancers were also found.

PMID- 1385947
TI  - Morphological and biochemical evidence for partial nuclear localization of
      annexin 1 in endothelial cells.
AB  - Using immunofluorescence, an affinity-purified anti-annexin-1 polyclonal antibody
      showed both cytoplasmic and nuclear staining, whereas antibodies against annexins
      2, 5 and 6 labelled almost exclusively the cytoplasm of cultured endothelial
      cells. This was further confirmed by immunogold labelling and electron microscopy
      using a monoclonal antibody, annexin 1 being detected close to the plasma
      membrane, in the cytoplasm, as well as inside the nucleus. Finally, using
      immunoblotting, purified nuclei were shown to contain annexin 1, which was not
      removed by EDTA treatment. These data open some new perspectives in the
      understanding of annexin function, including possible involvement in
      nucleoskeleton dynamics and regulation of proliferation through cell signalling.

PMID- 1385944
TI  - Endovascular surgery for peripheral arterial occlusive disease. A critical
      review.
AB  - Endovascular surgery is a new multidisciplinary field that applies the recently
      innovated techniques of angioscopy, intraluminal ultrasound, balloon angioplasty,
      laser, mechanical atherectomy, and stents. This field can be defined as a
      diagnostic and therapeutic discipline that uses catheter-based systems to treat
      vascular disease. As such, it integrates the subspecialties of vascular surgery,
      interventional radiology, interventional cardiology, and biomedical engineering
      for the common purpose of improving arterial hemodynamics. Endovascular surgery
      offers many potential benefits: long incisions are replaced with a puncture
      wound, the need for postoperative intensive care is significantly reduced, major
      cardiac and pulmonary complications from general anesthesia are side stepped, and
      the dollar savings could be dramatic as the need for intensive care unit and in
      hospital stay diminishes. Despite these technological advancements, endovascular
      surgery is still in its infancy and currently has limited applications. This
      review provides an updated summary of endovascular surgery today and addresses
      some of the obstacles still preventing its widespread use.

PMID- 1385948
TI  - Effects of ethanol and its fluorinated analogues on the calcium ATPase of
      sarcoplasmic reticulum.
AB  - The effects of ethanol, monofluoro- and trifluoroethanol on the hydrolysis of ATP
      and coupled Ca2+ translocation by sarcoplasmic reticulum Ca(2+)-ATPase (EC
      3.6.1.38) were measured. All three alcohols had parallel effects on the enzyme
      activities at concentrations up to 200 mM, suggesting a similar mechanism of
      action. 19F nuclear magnetic resonance spectroscopy was used to investigate their
      site of action in the purified enzyme.

PMID- 1385949
TI  - Interconversion of tetrahydrofolate cofactors to dihydrofolate induced by
      trimetrexate after suppression of thymidylate synthase by fluorodeoxyuridine in
      L1210 leukemia cells.
AB  - Previous studies from this laboratory demonstrated that marked suppression of
      thymidylate synthase activity is required to slow the rate of interconversion of
      tetrahydrofolate cofactors to dihydrofolate when dihydrofolate reductase is
      blocked by an antifolate. This finding is due to the high catalytic activity of
      thymidylate synthase within cells in comparison to the tetrahydrofolate cofactor
      pool size. In the present study, we assessed the rate of resumption of
      thymidylate synthase catalytic activity in terms of [3H]deoxyuridine
      incorporation into DNA and dihydrofolate generation from tetrahydrofolate
      cofactors following exposure of cells to fluorodeoxyuridine. Log phase L1210
      leukemia cells, incubated with fluorodeoxyuridine to abolish thymidylate synthase
      catalytic activity, were suspended into drug-free medium. Resumption of
      [3H]deoxyuridine incorporation into DNA was negligible; by 4 hr enzyme activity
      was still inhibited by approximately 98%. However, this was sufficient to
      interconvert all available tetrahydrofolate cofactors to dihydrofolate (T1/2
      approximately 2 hr) when dihydrofolate reductase was inhibited by the lipophilic
      antifolate trimetrexate. Interconversion of tetrahydrofolate cofactors to
      dihydrofolate correlated with a decline, then cessation, of purine synthesis as
      measured by the incorporation of [14C]formate into purine bases. These data
      suggest that an earlier than previously expected depletion of tetrahydrofolate
      cofactors with consequent inhibition of purine and other folate-dependent
      synthetic processes is likely to occur when antifolates are administered after a
      fluoropyrimidine.

PMID- 1385950
TI  - The effect of glycerol and 4-nitroquinoline 1-oxide on active oxygen formation in
      sub-cellular fractions of lung tissue.
AB  - Glycerol enhances pulmonary tumorigenesis in mice treated with 4-nitroquinoline 1
      oxide (4NQO). The present study shows that active oxygen formation by glycerol
      may be responsible for this enhanced tumorigenesis. Male ddY mice were treated
      with 4NQO and given a 5% glycerol solution instead of drinking water for up to 4
      weeks after 4NQO injection. There was no difference in NADH-dependent active
      oxygen formation of the mitochondria between the 4NQO- and 4NQO-plus-glycerol
      treated groups but the ratios of NADH- and NADPH-dependent active oxygen
      formation of the microsomes and nuclei of the 4NQO-plus-glycerol-treated group to
      the 4NQO-treated group increased with increasing time after 4NQO injection.
      Significant differences in the maximum NADH- and NADPH-dependent active oxygen
      formation were observed 2 or 4 weeks after 4NQO injection.

PMID- 1385951
TI  - Fatty acid conjugates of 2'-deoxy-5-fluorouridine as prodrugs for the selective
      delivery of 5-fluorouracil to tumor cells.
AB  - We have prepared a novel class of prodrugs by coupling 2'-deoxy-5-fluorouridine
      (5dFU) to oleic (18:1) and docosahexaenoic (22:6) acids, respectively. The
      cytotoxic activity of the drug and its conjugates (5dFU-18:1 and 5dFU-22:6) has
      been assayed in vitro upon HT-29, a colon carcinoma cell line of human origin.
      After short term (2-hr) treatments with the drugs, both fatty acid conjugates of
      5dFU showed cytotoxic activity in a dose-dependent way, while 5dFU alone was
      devoid of toxic effects within the whole range of concentrations (10-200 microM)
      tested. Following long term (24- or 48-hr) incubations only a fraction of the HT
      29 cell population was sensitive to 5dFU, the rest of the population being
      resistant even at the highest concentration tested (200 microM). In contrast,
      5dFU-oleic acid and, particularly, 5dFU-docosahexaenoic acids appeared toxic for
      the whole population of HT-29 cells under the same experimental conditions. The
      considerable gain in cell toxicity and, to a lesser extent, in selectivity
      resulted from the conjugation since the toxic effect of the drug alone was not
      modified when equimolar mixtures of 5dFU and fatty acids were assayed. These
      results confirm a previous study on the cytotoxicity of fatty acid derivatives of
      chlorambucil toward malignant lymphoblastoid cells and reinforce the potential
      use of fatty acid conjugates as efficient anti-tumor prodrugs.

PMID- 1385952
TI  - Identification of novel reduced pyridinium derivatives as synthetic co-factors
      for the enzyme DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2).
AB  - The enzyme DT diaphorase (NAD(P)H dehydrogenase (quinone), EC 1.6.99.2) is
      unusual in that it can utilize either NADH or NADPH as a co-factor for the
      reduction of its substrates. We have shown that the intact NAD(P)H molecule is
      not required and that other reduced pyridinium compounds can also act as co
      factors for DT diaphorase. The entire adenine dinucleotide portion of NAD(P)H can
      be dispensed with entirely and the simplest quaternary (and therefore reducible)
      derivative of nicotinamide, 1-methylnicotinamide, was as effective as NAD(P)H as
      a co-factor for the reduction of the quinone, menadione. Nicotinamide 5'-O
      benzoyl riboside was also as effective a co-factor as NAD(P)H, whilst
      nicotinamide ribotide and riboside have a higher Km, and decreased the kcat of DT
      diaphorase. Nicotinic acid derivatives had little activity. Kinetic analysis
      indicated that both nicotinamide ribotide and riboside may be interacting with
      the menadione binding site rather than the NAD(P)H site. Irrespective of the
      differences between the various reduced pyridinium derivatives in their ability
      to act as co-factors for the reduction of menadione by DT diaphorase, all the
      compounds that showed activity in this assay were equally effective co-factors
      for the reduction of the nitrobenzamide, CB 1954 (5-(aziridin-1-yl)-2,4
      dinitrobenzamide). The apparent Km of DT diaphorase for all these co-factors
      approached zero. It was concluded that co-factor binding is not a rate-limiting
      step in the nitroreductase activity of DT diaphorase.

PMID- 1385953
TI  - Lipoprotein(a) at birth, in blacks and whites.
AB  - It has been shown that blacks have considerably higher concentrations than whites
      of lipoprotein(a) (Lp(a)), which has been identified as an independent risk
      factor for coronary heart disease, vein graft restenosis, and cerebrovascular
      disease. Smaller differences in Lp(a) concentrations have been noted between
      males and females. To examine whether gender and race differences are already
      detectable at birth, we examined Lp(a) concentrations in cord blood samples of
      109 black (49 male and 60 female) and 123 white (67 male and 56 female) newborns.
      Maternal age, gestational age, fetal maturity indicators, weight, height and head
      circumference were analyzed as covariates. For race and sex combined, the mean
      Lp(a) concentration was 4.0 mg/dl (S.D. of 3.94 mg/dl), approximately 5-fold
      lower than that observed in adults. No statistically significant differences were
      found between race or gender groups. The cross-sectional examination of serum
      Lp(a) concentrations of 221 infants, children and adults showed a gradual
      increase in Lp(a) concentrations from birth to adult values by the second year of
      life. We conclude that the system responsible for the production and control of
      Lp(a) concentration is not yet mature--or has not yet been challenged--at birth.

PMID- 1385954
TI  - Lipoprotein(a) in subjects with familial defective apolipoprotein B100.
AB  - The plasma lipoprotein(a) (Lp(a)) concentration and apolipoprotein(a) (apo(a))
      phenotype were determined in the members of two families affected with familial
      defective apo B100 (FDB), resulting from the Arg3500----Gln mutation in apo B
      that disrupts binding to LDL receptors. Eleven different phenotypic species of
      apo A were identified, five of which were present in both families. Although
      there was a general increase in Lp(a) concentration as the size of the
      predominant apo(a) component decreased, there was considerable variability and in
      three clear instances the concentration of an inherited phenotypic species was
      atypically low. In five cases where a direct comparison could be made, the plasma
      Lp(a) concentration was significantly higher in heterozygous FDB subjects than in
      their non-FDB siblings or close relatives with the same phenotype. However, in
      vitro competition studies using purified Lp(a) that had been reduced with
      dithiothreitol to remove the apo(a) component, indicated that the Lp(a) from FDB
      heterozygotes contained a smaller proportion of defective particles than their
      LDL. Lp(a) particles containing normal and binding-defective apo B were present
      at approximately the same concentration, suggesting that the increase in Lp(a)
      concentration observed in FDB subjects could not be explained by the inability of
      the particles containing the defective apo B100 to be cleared through LDL
      receptor mediated processes.

PMID- 1385955
TI  - Multivariate genetic analysis of high density lipoprotein particles.
AB  - The aim of this study was to investigate the effect of genetic factors on three
      components of plasma high density lipoproteins, HDL-cholesterol (HDL-C),
      apolipoprotein A-I (apo A-I) and lipoprotein particle Lp A-I (Lp A-I), which
      contains apo A-I but not apo A-II. These analyses were carried out on 106 nuclear
      families with one or more children (407 subjects) who volunteered for health
      screening at the Center for Preventive Medicine, Vandoeuvre, France. After
      adjustment by stepwise multiple linear regression analysis for age, gender,
      weight, height, ponderosity, alcohol consumption, smoking habits, and hormonal
      treatment in females, a multifactorial model (considering the effect of
      polygenes, individual, specific, environmental and common household factors) was
      fitted to each variable separately. The hypothesis of no common household effects
      was accepted for each of the traits. The contribution of genetic factors to inter
      individual variance was larger than the contribution of environmental factors for
      apo A-I (h2 = 0.81) and Lp A-I (h2 = 0.63) but not for HDL-C (h2 = 0.44).
      Bivariate analyses were carried out by parameterizing covariance components
      between traits. The genetic correlations were always significantly different from
      zero. They were estimated to be 0.73 between HDL-C and apo A-I, 0.40 between HDL
      C and Lp A-I, 0.51 between apo A-I and Lp A-I. These results suggest that HDL-C,
      apo A-I and Lp A-I are only in part affected by the same genes and that the
      measurement of lipids as well as the apo A-I and Lp A-I gives complementary and
      different information on the metabolic and genetic aspects.

PMID- 1385956
TI  - Arterial response to mechanical injury: balloon catheter de-endothelialization.
AB  - Coronary angioplasty has been used clinically for over a decade. Its initial
      promise as an alternative to coronary bypass surgery has only partially been
      fulfilled because of the high rate of post-operative restenosis. A number of
      animal models have been devised to study this phenomenon and although none is
      entirely satisfactory, they have, together with recent advances in molecular
      biology provided an insight into the cellular mechanisms that may contribute to
      this complication. This knowledge may ultimately lead to a means of therapeutic
      intervention. This review summarises our present understanding of the pathology
      of post-angioplasty re-stenosis as revealed by studies using the balloon catheter
      de-endothelialization model, and discusses some of the intervention strategies
      that have been attempted.

PMID- 1385957
TI  - Age dependency of cystathionine beta-synthase activity in human fibroblasts in
      homocyst(e)inemia and atherosclerotic vascular disease.
AB  - In order to clarify whether cystathionine beta-synthase (CBS) could differentiate
      groups of patients with various vascular diagnosis, CBS was studied in cultured
      human skin fibroblasts from 99 human subjects diagnosed as homozygotes or
      heterozygotes for CBS deficiency or suffering from atherosclerotic vascular
      disease or Down's syndrome (prone to less atherosclerosis). In addition,
      embryonic human skin fibroblasts and controls were analysed for CBS. We found
      significant group differences but the overlap in the hetero- and homozygotes for
      CBS deficiency was too extensive to allow any individual diagnosis based on cell
      culture studies. CBS activity was significantly lower in the atherosclerotic
      patients as compared to control subjects. The difference was mostly due to much
      higher CBS activity in the younger controls. Age dependency was markedly
      emphasized by very high values from embryonic cells. A strong negative
      correlation was noted for age and CBS activity in control subjects but not in the
      atherosclerotic patients. The results are important for the discussion of
      homocysteine in atherosclerosis and point to the importance of donor age on CBS
      activity in cultured cells. In addition, diagnosis of hetero-homozygosity for CBS
      activity is not possible on an individual basis by this method. Further studies
      in cell culture systems are needed to investigate if young patients (less than 45
      years old) with atherosclerotic disease could be identified by low CBS activity
      in fibroblast cultures as indicated by this study.

PMID- 1385958
TI  - Correlation of apolipoprotein(a) isoproteins with Lp(a) density and distribution
      in fasting plasma.
AB  - Lp(a) is an LDL-like lipoprotein which contains an additional apolipoprotein
      called apo(a). Apo(a) exhibits a significant size polymorphism and its size is
      inversely correlated with plasma Lp(a) levels. We investigated the distribution
      of different apo(a) isoproteins in lipoprotein density fractions. Fasting plasma
      samples were subjected to non-equilibrium density gradient ultracentrifugation.
      After SDS-PAGE and anti-apo(a) immunoblotting, apo(a) concentrations in
      individual density fractions were evaluated by densitometry. In series I,
      analysis of selected density fractions from 35 coronary heart disease (CHD)
      patients demonstrated that although most of the apo(a) was present in the Lp(a)
      density range, apo(a) was consistently found in both the VLDL and IDL fractions
      as well. In series II, density fractions from 9 normolipidemic subjects with 6
      different apo(a) isoproteins were evaluated. A strong association between the
      size of the apo(a) isoprotein and the density of the associated Lp(a) particle
      was established (r = 0.976, P less than 0.001). Lp(a) densities ranged from 1.057
      g/ml for the B isoprotein to 1.09 g/ml for the S5 isoprotein. Overall, 75% of the
      total apo(a) was detected in the Lp(a) density range (d = 1.05-1.12 g/ml), with
      9% and 10% in the LDL (d = 1.019-1.05 g/ml) and HDL (d = 1.12-1.21 g/ml)
      fractions, respectively. VLDL contained an average of 4% of the total apo(a) in
      fasting normolipidemic plasma. Two hypertriglyceridemic subjects had
      substantially greater amounts of apo(a) in the fasting triglyceride-rich
      fraction. The results of this study indicate that the size of the apo(a)
      isoprotein strongly influences the density of its associated Lp(a) particle and
      that apo(a) is consistently found in the triglyceride-rich lipoproteins of
      fasting plasma.

PMID- 1385959
TI  - Effects of niceritrol on levels of serum lipids, lipoprotein(a), and fibrinogen
      in patients with primary hypercholesterolemia.
AB  - Thirty-three consecutive unselected patients with primary hypercholesterolemia
      received niceritrol 1.5 g daily for 12 weeks, with the effect of administering
      divided dose (twice daily (b.i.d.) and three times daily (t.i.d.)) evaluated. The
      serum concentrations of lipoprotein(a) (Lp(a)), lipids, the major apolipoproteins
      (apo), cholesteryl ester transfer activity and fibrinogen were determined before
      and after treatment. The b.i.d. and t.i.d. regimens each significantly reduced
      the serum levels of total cholesterol and triglyceride. The mean changes in serum
      lipids and lipoproteins did not differ significantly between the two groups.
      After 12 weeks of treatment, there was a significant decrease in total plasma
      cholesterol, triglyceride, low density lipoprotein cholesterol, apo A-II, apo B
      and fibrinogen and an increase in the high density lipoprotein cholesterol
      levels. Although the serum level of Lp(a) did not change in every patient,
      niceritrol significantly reduced the serum Lp(a) level in those with an initially
      high level of Lp(a) (greater than or equal to 20 mg/dl).

PMID- 1385960
TI  - Effects of the gonadotrophin-releasing hormone agonist 'Zoladex' upon pituitary
      and gonadal function in hypogonadal (hpg) male mice: a comparison with normal
      male and testicular feminized (tfm) mice.
AB  - Hypogonadal (hpg) mutant mice, with a congenital deficiency of hypothalamic
      gonadotrophin-releasing hormone (GnRH), and testicular feminized (tfm) mice,
      which lack a functional androgen receptor, were used to study the effects of the
      potent GnRH agonist 'Zoladex' (ICI 118630; D-Ser (Bu(t))6, Azgly10-GnRH) on
      pituitary and gonadal function. Zoladex (0.5 mg) in a sustained-release lactide
      glycolide copolymer depot was administered subcutaneously under anaesthesia and
      was left in place for 7 days, after which time the effects of the drug upon
      pituitary and serum gonadotrophin concentrations, glycoprotein hormone subunit
      mRNAs and testicular morphology were investigated. At the pituitary level,
      Zoladex treatment resulted in a substantial reduction in LH content in normal
      males, and LH content was depressed in hpg mice even below the basal levels
      normally found in these mutants. Pituitary LH content in the Zoladex-treated
      animals was depressed in the tfm groups, but not to the same levels as those
      found in the normal and castrated normal mice. Zoladex treatment at the time of
      castration prevented the post-operative elevation in serum LH associated with
      castration alone. In the androgen-deficient tfm mouse, Zoladex did not depress
      the normally elevated serum LH levels. Serum LH in the hpg animals was, in all
      cases, below the limit of detection of the assay. Pituitary FSH content was
      depressed into the hpg range in both the normal and castrated animals, but there
      was no further depression in the hpg mice. The pituitary content was reduced in
      the tfm mice, again the effects not being as dramatic as in the normal and
      castrated animals. Serum FSH content, as measured by radioimmunoassay, was
      depressed by 50% in normal mice; there was no reduction in the hpg mice, however.
      With regard to pituitary gonadotrophic hormone gene expression, Zoladex
      administration to normal mice caused a dramatic reduction in LH beta mRNA
      content, to a level approximating that found in untreated hpg mice. The drug also
      depressed LH beta mRNA in the castrated group to the hpg range when given at the
      time of castration, whereas in untreated castrated mice there was a significant
      increase in LH beta mRNA. In the tfm mouse, which can be considered as a model
      for long-term failure of androgen feedback, Zoladex again induced a fall in LH
      beta mRNA, but not to the same extent as in the normal and normal castrated
      group. Zoladex had no effect on the already low levels of LH beta mRNA found in
      hpg mice.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1385961
TI  - [Laparoscopic cholecystectomy in pediatrics. A report of the first case in the
      Mexican literature].
AB  - The authors present the case of a 9.8-year-old girl with 5 a month history of
      epigastric pain which was due to gallstones as demonstrated by ultrasound. After
      an extensive work-up failed to reveal associated hematologic problems, she was
      successfully treated by laparoscopic cholecystectomy, resulting in complete
      recovery, hospitalization of 22 hours and return to school three days after major
      surgery. We could not find references of laparoscopic cholecystectomy in the
      pediatric age group in the Mexican literature and only 3 in English language
      publications. In cases of cholelithiasis without associated diseases in children,
      the operation of choice should be laparoscopic cholecystectomy.

PMID- 1385962
TI  - Disordered sodium and water in neurosurgery.

PMID- 1385963
TI  - Atrial and digitalis-like natriuretic hormones in essential hypertension under
      functional loading.
AB  - To assess the relation of the two natriuretic hormones, atrial natriuretic
      peptide (ANP) and digitalis-like natriuretic factor (DLF), to hypertension,
      levels of ANP and DLF were measured under basal conditions and after salt and
      water loading in 31 normal subjects and 36 and 57 patients with Stage I or II
      essential hypertension (EH). DLF levels were higher in normal women than men; in
      EH-II patients, DLF levels were elevated among men but subnormal in women (P less
      than .02) and rose with water loading in both genders. In all groups ANP levels
      tended to be higher in women. Water loading increased ANP levels in EH-I patients
      (P less than .001) and caused less marked increases of ANP in control and EH-II
      women and men. ANP also tended to increase with salt loading. Both DLF and ANP
      were related to blood pressure in the subject groups (r = 0.75 to 0.96 and r =
      0.27 to 0.75, respectively) and were also related to each other (r = 0.20 to
      0.47). The role of ANP and DLF in hypertension are likely to be compensatory and
      directed against water-electrolyte metabolism disorders associated with elevated
      arterial pressure.

PMID- 1385964
TI  - Magnetic resonance imaging of cardiac hypertrophy in malignant arterial
      hypertension.
AB  - The major target organs that become damaged as a consequence of long-standing
      arterial hypertension are the kidneys, heart, and brain. Left ventricular
      hypertrophy (LVH) cannot be considered only as an adaptive process to elevated
      blood pressure (BP), and the heart is also a major target organ in malignant
      arterial hypertension (MH). Magnetic resonance (MR) was used as a method for
      visualization of the heart in 68 patients with MH including 18 with essential
      hypertension, 16 with chronic glomerulonephritis, 13 with chronic pyelonephritis,
      16 with renovascular hypertension, eight with adrenal tumors, and in 20 healthy
      volunteers (as a comparison group). Electrocardiogram-gated, double spin-echo
      magnetic resonance imaging was performed to image the right and left ventricles
      (RV and LV), interventricular septum, apex and LV posterior wall, left atrium,
      and aortic root. In all the patients, symmetric LV hypertrophy was registered and
      in the most severe cases LV wall thickness was more than 20 mm. There was no LV
      cavity enlargement or local contractility abnormalities. There was close
      correlation of LVH and diastolic BP. The degree of LVH and diastolic dimensions
      of the LV differed between etiologies of MH. These findings show that different
      pathophysiologic mechanisms of development of MH influence the processes of
      myocardial hypertrophy. The highly informative yield of MR tomography for
      evaluating structural and functional changes of the heart under MH must be
      underlined.

PMID- 1385965
TI  - Effects of sertraline and citalopram given repeatedly on the responsiveness of 5
      HT receptor subpopulations.
AB  - The effect of repeated treatment (5 and 10 mg/kg, po, twice daily, 14 days) with
      sertraline and citalopram (antidepressants which selectively inhibit the reuptake
      of 5-hydroxytryptamine (5-HT)) on the responsiveness of different 5-HT receptors
      to their agonists, was examined in rats and mice. Sertraline and citalopram (both
      at a dose 5 and 10 mg/kg) antagonized (the first one more potently) the
      hypothermia induced in mice by 8-OH-DPAT (a 5-HT1A agonist), but not the
      behavioural syndrome induced in rats by this substance. The m
      chlorophenylpiperazine-induced hypothermia in mice (a 5-HT1B effect) was
      increased by sertraline and citalopram (only in a dose of 10 mg/kg). Both
      antidepressants, given repeatedly (as well acutely) attenuated exploratory
      hypoactivity induced in rats by m-chlorophenylpiperazine (a 5-HT1C effect). L-5
      HTP-induced head twitches in mice (5-HT2 effect) were antagonized dose
      dependently by both repeated sertraline and citalopram. Both antidepressants
      (citalopram only in higher dose) reduced the fenfluramine-induced hyperthermia in
      rats (5-HT2 effect). The results indicate that sertraline and citalopram given
      repeatedly decrease the responsiveness of 5-HT1A (presynaptic) and 5-HT2
      receptors but increase the responsiveness of 5-HT1B receptors to respective
      agonists.

PMID- 1385966
TI  - Complete rescue of photoreceptor dysplasia and degeneration in transgenic retinal
      degeneration slow (rds) mice.
AB  - retinal degeneration slow (rds) is a semidominant mutation of mice with the
      phenotype of abnormal development of rod and cone photoreceptors, followed by
      their slow degeneration. The rds gene has been putatively cloned and its novel
      protein product initially characterized biochemically. In the present study we
      undertook to correct in vivo the retinal phenotype of mice with the rds mutation.
      We assembled a transgene containing a regulatory segment of the opsin gene
      positioned upstream of the wild-type rds coding region. Mice from three
      transgenic lines, homozygous for the rds mutation, were analyzed for expression
      of the transgene and for their retinal phenotypes. In two high expressing lines,
      we observed complete reversion to wild-type retinal morphology. In a third, low
      expressing line, we observed a retinal phenotype intermediate between wild type
      and rds/rds, suggesting partial rescue of the mutation. These results constitute
      formal proof that we have cloned the rds gene.

PMID- 1385967
TI  - [Proto-oncogenes, stress proteins and hypertensive cardiopathy].

PMID- 1385968
TI  - A meta-analysis of randomized trials of fish oil in prevention of restenosis
      following coronary angioplasty.
AB  - The efficacy of fish oil in decreasing restenosis following percutaneous
      transluminal coronary angioplasty (PTCA) remains controversial despite seven
      published reports of randomized trials involving 951 patients. We performed a
      meta-analysis to determine whether these trials, viewed in aggregate, demonstrate
      a significant benefit. We evaluated rates of restenosis two to 12 months after
      PTCA and calculated an estimate of the overall effect and 95% confidence interval
      (CI). The typical odds ratio (treatment versus control) was 0.71 (95% CI 0.54,
      0.94), P = 0.016 (two-tailed). The data show a strong and highly significant (P
      less than .0001) relationship between daily fish oil dose and gastrointestinal
      side effects. While compatible with a small to moderate benefit of fish oil on
      rates of restenosis, these results require confirmation in a randomized clinical
      trial large enough to distinguish reliably between a clinically meaningful
      benefit and a null result.

PMID- 1385969
TI  - [Significance of plasma atrial natriuretic peptide measurement during the
      management of hyponatremia in neurosurgical patients].
AB  - We have examined the total number of admitted cases to clarify the pathogenesis
      of hyponatremia during the management of neurosurgical patients. We experienced
      32 cases of hyponatremia during the past year by measuring the sodium balance and
      atrial natriuretic peptide (ANP) level. According to these two factors, we
      divided the cases into three groups. The first group shows normal ANP levels in
      spite of hyponatremia. Low administration of the sodium was thought to be the
      cause in these cases. The second group shows the elevated ANP levels with a
      positive sodium balance. Elevated circulatory volume due to the inadequate level
      of antidiuretic hormone and mild heart and/or kidney failures cause these
      conditions. Water restriction and/or diuresis were effective methods in the
      management of the cases. The last group shows the elevated ANP levels with a
      negative sodium balance. There is a statistically significant negative
      correlation between sodium balance and the ANP level. Marked natriuresis due to
      the elevated ANP causes the decrement of the circulatory volume in these cases.
      Pathogenesis of the last group is very important in the management of
      neurosurgical patients in an acute state, especially in subarachnoid hemorrhage
      cases. The decrement of the systemic circulatory volume would jeopardize the
      patient's neurological condition. In this group, water restriction that has been
      commonly recommended is contraindicated. Satisfactory water and sodium
      replenishment seems to be the best recommended treatment for this group.

PMID- 1385970
TI  - The effect of ACE inhibitors and atrial natriuretic factor on the cardiorenal
      axis in man.

PMID- 1385971
TI  - Inhibition of inhaled metabisulphite-induced bronchoconstriction by inhaled
      frusemide and ipratropium bromide.
AB  - 1. The effect of inhaled frusemide and high dose inhaled ipratropium bromide on
      bronchoconstriction induced by inhaled metabisulphite was studied in 10 atopic
      volunteers. 2. Frusemide (40 mg), ipratropium bromide (0.5 mg) or saline placebo
      were administered by nebuliser in a double-blind fashion, prior to construction
      of a dose-response curve to metabisulphite (2.5-100 mg ml-1). 3. Geometric mean
      of the provocative dose of metabisulphite that caused a 35% fall in specific
      airways resistance (sGaw) after placebo was 13 (95% confidence intervals CI 4-36
      mumol) compared with 36 (16-78) mumol after ipratropium bromide and 45 (22-94)
      mumol after frusemide. 4. Mean maximum fall in sGaw was 49 (40-57)% after
      placebo, 11 (0-22)% after frusemide and -1 (-25-22)% after ipratropium bromide.
      5. Frusemide significantly protected against metabisulphite induced
      bronchoconstriction (P less than 0.005). The protection from high dose
      ipratropium bromide was also significant (P less than 0.05), but the response was
      more variable between subjects.

PMID- 1385973
TI  - Hepatitis B. Immunization of newborn infants.

PMID- 1385974
TI  - Humoral immunity in Down's syndrome.
AB  - Carried out on 57 outpatients, the study was aimed to prove the existence of a
      disgammaglobulinemia in Down's syndrome. The event could not be attributed to
      hospitalization. Data indicate increased A and G immunoglobulinemias. In
      agreement with other authors Ig A level was found to be very high especially
      after the age of 5. Ig M titre in patients was reduced in comparison with that of
      the controls, regardless of the age group. Increase timing of IgA and Ig G
      concentrations tends to be more marked for the Ig A fraction. In patients ranging
      from 0 to 5 years the Ig A serum level is deficient.

PMID- 1385972
TI  - Agreement and reproducibility of the estimates of cardiovascular function by
      impedance cardiography and M-mode echocardiography in healthy subjects.
AB  - The reproducibility and agreement of the estimates of stroke volume (SV), cardiac
      output (CO) and total peripheral resistance (TPR) by transthoracic impedance
      cardiography (ZCG) and M-mode echocardiography (ECHO) were analyzed before and
      after the placebo-controlled administration of ascending doses of isosorbide
      dinitrate and nicorandil in 12 healthy subjects. There was no biostatistical
      agreement between the two methods in estimating cardiovascular function either
      before or after dosing (ZCG estimated substantially larger SV, CO and lower TPR).
      But, ZCG and ECHO estimated about similar overall treatment related changes
      (across treatments and periods) and reached substantially better agreement when
      the values were expressed as ratio of the baseline before dosing. Such
      improvement did not occur when the data were expressed as arithmetic difference
      from baseline. In spite of the improvement of agreement by expressing the data as
      ratio of baseline, the coefficients of reproducibility between the two methods
      (circa 25% of baseline) remained too large to judge the methods interchangeable.

PMID- 1385975
TI  - Annexin I-mediated vesicular aggregation: mechanism and role in human
      neutrophils.
AB  - Whole cytosol isolated from human neutrophils was found to accelerate the Ca(2+)
      dependent fusion of phospholipid vesicles with neutrophil plasma membranes as
      measured by several fluorescence resonance energy transfer lipid dilution assays
      or by the fate of an encapsulated aqueous soluble fluorophore. The Ca2+
      (threshold of 2-10 microM) and protein concentration dependencies for fusion
      mediated by purified human neutrophil annexin I (lipocortin I), recombinant
      annexin I and des(1-9)annexin I showed behavior similar to that of whole cytosol.
      A monoclonal antibody against the N-terminal region of annexin I strongly
      inhibited the action of isolated annexins as well as whole cytosol, indicating
      that annexin I is the major activity of this type in whole neutrophil cytosol and
      that it functions even in this complex mixture of proteins. Residual Ca(2+)
      dependent fusion activity in the absence of cytosol or annexin I was not
      inhibited by several antibodies against annexin I, implicating an as yet unknown
      protein. Kinetic analysis of liposomal fusion showed that annexin I, as in the
      case of synexin, accelerates aggregation of vesicles but not the actual fusion
      event per se. The disposition of annexin I in liposomal aggregates was studied by
      monitoring binding of the protein with a pyrene-phospholipid and by
      simultaneously monitoring vesicular aggregation by turbidity. An antibody to the
      N-terminus of annexin I inhibited vesicular aggregation but not binding,
      suggesting that initial binding of annexin I is similar to that of annexin V. A
      relatively small proportion of the bound annexin was involved in intervesicular
      linkage, and no exchange of bound annexin to subsequently added vesicles was
      observed. The lack of extensive contact between lipids of aggregated vesicles was
      supported by a lack of energy transfer between phospholipid probes on separate
      aggregating vesicles. Covalent linkage of maleimidyl or photoaffinity
      phospholipid derivatives with annexin I in vesicular aggregates did not allow
      complete disaggregation of vesicles by EDTA, suggesting that monomers of annexin
      I can contact two membranes simultaneously at the point of intervesicular
      linkage. These data are discussed in terms of possible models for the structure
      of this site.

PMID- 1385976
TI  - Zero-length crosslinking between subunits delta and I of the H(+)-translocating
      ATPase of chloroplasts.
AB  - Treatment of spinach thylakoids with 1-ethyl-3-(dimethylaminopropyl)-carbodiimide
      (EDC)/N-hydroxysulfosuccinimide (sulfo-NHS) induced formation of a zero-length
      crosslink of an apparent molecular mass of 38 kDa. This product was shown, by
      immunodetection, to consist of subunit delta of CF1 and subunit I of CF0. The
      crosslink was isolated by preparative SDS gel electrophoresis and subjected to
      cyanogen bromide cleavage. Electrophoretic and immunological analysis of the
      resulting peptides suggested that the crosslink was formed between a glutamyl or
      aspartyl residue at the C-terminal end of subunit I and a basic amino acid of
      subunit delta in the range between Val-1 to Met-165. Treatment of thylakoids with
      EDC/Sulfo-NHS resulted in inhibition of photophosphorylation and CF0CF1-catalyzed
      ATP hydrolysis without affecting formation of a proton gradient related to
      phenazine methosulfate-mediated cyclic electron transport. Inhibition of H+
      transport-coupled ATP hydrolysis was more pronounced than non-coupled methanol
      stimulated ATP hydrolysis. The results suggest that subunits delta and I form a
      connection between the partial complexes CF1 and CF0 in situ. Crosslinking of the
      two subunits may impede the translocation of protons through CF0CF1.

PMID- 1385977
TI  - Molecular genetic studies of complex I in Neurospora crassa, Aspergillus niger
      and Escherichia coli.

PMID- 1385978
TI  - ATP synthase: structure-function relationships.
AB  - Recent work has focused on obtaining a better understanding of the three
      dimensional structural relationships between the alpha and beta subunits of the
      F1 moiety and the location of nucleotide binding domains within these subunits.
      Four types of approach are currently being pursued: X-ray crystallographic,
      chemical, molecular biological and biochemical. Here we briefly review some of
      the major conclusions of these studies, and point out some of the problems that
      must be resolved before an adequate model that relates structure to function in
      the ATP synthase molecule can be formulated.

PMID- 1385979
TI  - F-type or V-type? The chimeric nature of the archaebacterial ATP synthase.
AB  - Archaebacterial plasma membranes contain an ATPase acting in vivo as a delta mu
      H(+)-driven ATP synthase. While functional features and their general structural
      design are resembling F-type ATPases, primary sequences of the two large
      polypeptides from the catalytic part are closely related to V-type ATPases from
      eucaryotic vacuolar membranes. The chimeric nature of archaebacterial ATPase from
      Sulfolobus was investigated in terms of nucleotide interactions and related to
      specific sequence parameters in a comparison to well known F- and V-type ATPases.
      The study disclosed a general difference of F- and V-type ATPases at one class of
      the nucleotide binding sites.

PMID- 1385980
TI  - The ATPases of Propionigenium modestum and Bacillus alcalophilus. Strategies for
      ATP synthesis under low energy conditions.
AB  - In Propionigenium modestum, ATP synthesis is coupled via delta mu Na+ to the
      decarboxylation of (S)-methylmalonyl-CoA. The low energy yield of this reaction
      implies that approx. 4 decarboxylation cycles are necessary to synthesize 1
      molecule of ATP. Theoretical considerations in accord with experimental results
      suggest ATP synthesis in P. modestum at delta mu Na+ = -110 mV. Other anaerobic
      bacteria synthesize ATP at a delta mu H+ of similar size and alkaliphilic
      bacteria at pH 10.3 have a delta mu H+ of only -103 mV. In these cases, the
      H+(Na+) to ATP stoichiometry must be at least 4.

PMID- 1385981
TI  - Subunit c of F1F0 ATP synthase: structure and role in transmembrane energy
      transduction.

PMID- 1385982
TI  - Chemical modification of cyclomaltodextrin glucanotransferase from Bacillus
      circulans var. alkalophilus.
AB  - Counting of integral numbers of cysteine residues of the reduced and denaturated
      form of cyclomaltodextrin glucanotransferase (CGTase) from Bacillus circulans
      var. alkalophilus (ATCC 21783) showed two cysteine residues per enzyme molecule.
      Titrations of the enzyme with 5,5'-dithiobis-(2-nitrobenzoic acid) led to the
      same result. No free SH-group was detected in denatured form of CGTase,
      indicating that the two cysteine residues are linked by one disulfide bridge.
      Cyclizing activity of the GdmCl-denaturated and reduced enzyme was 13% of that of
      the native one. Incubation of CGTase with diethylpyrocarbonate (DEP) showed a
      pseudo-first-order inhibition with second-order rate constant of 3.2 M-1 s-1.
      Reaction with hydroxylamine and spectroscopic studies implied that inactivation
      of CGTase by DEP is due to modification of one histidine residue concomitantly
      with a 50% decrease in the cyclizing activity (t1/2 = 10.8 min). The inhibition
      was partially reversible. CGTase was protected against inactivation by alpha- and
      beta-cyclodextrins suggesting that the modified histidine residue is at or near
      the active site. Conversion of starch with DEP-modified enzyme resulted in a
      decreased formation of cyclodextrins while the relative amount of reducing sugars
      increased. Preliminary results on modification of CGTase with other reagents,
      e.g., Woodward's reagent K, 2,3-butanedione and carbodiimide are included.

PMID- 1385984
TI  - Tissue response to intraperitoneal implants of polyethylene oxide-modified
      polyethylene terephthalate.
AB  - Polyethylene terephthalate films surface modified with polyethylene oxide of mol
      wt 18,500 g/mol (18.5 k) by a previously described technique, were implanted in
      the peritoneal cavity of mice, along with their respective untreated controls,
      for periods of 1-28 d. The implants were retrieved and examined for tissue
      reactivity and cellular adherence. The control polyethylene terephthalate
      surfaces showed an initial inflammatory reaction followed by an extensive
      fibrotic response with a mean thickness of 60 microns at 28 d. By contrast,
      polyethylene oxide-modified polyethylene terephthalate showed only a mild
      inflammatory response and no fibrotic encapsulation throughout the implantation
      period: at 28 d a cellular monolayer was observed. Apparently either the
      polyethylene oxide-modified surface was stimulating less inflammation, which was
      in turn stimulating less fibroblastic overgrowth, or the cellular adhesion to the
      polyethylene oxide-modified surface was too weak to support cellular multilayers.

PMID- 1385983
TI  - Surface-immobilized polyethylene oxide for bacterial repellence.
AB  - Polyethylene terephthalate films were surface-modified with polyethylene oxide
      (18,500 g/mol) using a solution technique described previously. These films were
      investigated for their resistance to bacterial adhesion. Three bacterial strains
      most commonly associated with implant infections, Staphylococcus epidermidis,
      Staphylococcus aureus and Pseudomonas aeruginosa, were cultured in tryptic soya
      broth, human plasma and human serum on the polymeric substrates. Significant
      reductions (between 70 and 95%) in adherent bacteria were observed on the
      polyethylene oxide-modified substrates compared to the untreated control
      polyethylene terephthalate. Surface modification with polyethylene oxide may
      reduce the risk of implant-associated infections. Plasma fibrinogen was observed
      to play an important role in the adhesion of all three of these species on both
      the polyethylene oxide-modified and control polyethylene terephthalate materials.

PMID- 1385985
TI  - Acute upregulation of interleukin-1 receptor by ligand.
AB  - In this study we have investigated the effect that interleukin 1 (IL-1) has on
      cell surface IL-1 receptor expression in the murine thymoma cell line, EL4 6.1.
      These cells express IL-1 receptors with both high affinity (Kd = 65 pM, 986
      receptors/cell) and low affinity (Kd = 14.5 nM, 10,417 receptors/cell). The high-
      and low-affinity receptors are indistinguishable by crosslinking studies
      performed at both high and low ligand concentrations. However, the two affinity
      states could be functionally distinguished on the basis of their internalization
      of ligand. Receptor-mediated endocytosis was dependent upon the concentration of
      ligand bound to the cells. In the presence of low IL-1 concentrations receptor
      mediated endocytosis was slow, whereas at high IL-1 concentrations, endocytosis
      was more rapid. Furthermore, receptor-mediated endocytosis of IL-1 did not result
      in downregulation of surface IL-1 receptors. Indeed, both kinetic and equilibrium
      binding studies revealed that pre-incubation of cells with IL-1 alpha resulted in
      an acute upregulation of 125IL-1 alpha binding to high affinity surface receptors
      in a time and energy dependent manner. Examination of the association kinetics
      suggested that increased binding was not attributable to positive co-operativity
      of the high affinity IL-1 receptor, but was due to increasing IL-1 receptor
      number. This observation was confirmed by equilibrium binding studies. Moreover,
      receptor numbers were not enhanced by de novo synthesis, nor release of receptors
      from an intracellular pool. The observed increases in surface ligand binding were
      most probably due to conversion of the surface pool of low affinity receptors
      into high affinity receptors.

PMID- 1385987
TI  - Cloning and chromosome mapping of the human interleukin-1 receptor antagonist
      gene.
AB  - By screening a human genomic library with an interleukin-1 receptor antagonist
      (IL-1ra) cDNA probe, we have isolated a 15 kb clone which contains the entire
      coding region of the gene as expressed in monocytes, and includes 6 kb of 5'
      upstream sequence. The gene contains four exons which code for the secreted form
      of the IL-1ra, however, our clone does not contain the alternative first exon
      used to generate an intracellular form of the protein as the protein as found in
      epithelial cells. Analysis of the sequence reveals a consensus TATA box, and
      three Alu repeats, two of which are in the upstream region and one in intron 3.
      The sequence also reveals an 86 bp motif tandomly repeated four times within
      intron 2, and may reflect the polymorphism known to exist in this region of the
      gene. By in-situ fluorescence hybridization we have shown that the IL-1ra gene is
      found on the long arm of chromosome 2 and maps to 2q13-14.1. Previous studies
      have revealed that IL-1 alpha, and IL-1 beta and both type I and type II forms of
      the IL-1 receptor all map close to this region of chromosome 2.

PMID- 1385986
TI  - Effects of human anti-IL-1 alpha autoantibodies on receptor binding and
      biological activities of IL-1.
AB  - Immunoglobulin G (IgG) antibodies to interleukin 1 alpha (IL-1 alpha) are
      frequently found in the sera of healthy human individuals. The effects of these
      autoantibodies on receptor binding and biological activities of human IL-1 were
      tested. Using the murine T-lymphocyte line NOB-1, human thyrocytes and human
      foreskin fibroblasts, the antibodies competitively inhibited the biological
      activity of human recombinant IL-1 alpha (rIL-1 alpha). The degree of inhibition
      correlated with 125I-rIL-1 alpha binding to IgG in different immunoglobulin
      preparations and in individual sera. These antibodies also neutralized the IL-1
      activity of isolated membrane fragments and lysates of human blood monocytes
      activated by lipopolysaccharide. In contrast, the supernatant IL-1 activity was
      not affected. Stronger inhibition of biological activity and cell binding of 125I
      rIL-1 alpha was obtained with NOB-1 cells than with human thyrocytes. The
      antibodies failed to interfere with the biological activity of rIL-1 beta. It is
      concluded that IgG autoantibodies of IL-1 alpha in the sera of healthy humans
      selectively inhibit the biological activity of the soluble and membrane
      associated forms of IL-1 alpha in vitro, and that the degree of biological
      inhibition afforded by these antibodies depends upon the target cell.

PMID- 1385988
TI  - Molecular characterization of the interleukin-1 receptor (IL-1R) on monocytes and
      polymorphonuclear cells.
AB  - Primary human monocytes and monocytic cells express an interleukin 1 receptor (IL
      1R) which is similar in molecular weight and IL-1 binding characteristics to the
      IL-1R expressed on B lymphocytes (type II). Northern blot analysis of monocytic
      cells using a cDNA probe from the recently isolated type II IL-1R indicates that
      this mRNA is detectable by 4 h and accumulates for at least 24 h following
      treatment with IL-1R inducing drugs. The time course of induction of this mRNA is
      slower than that of the type I IL-1R mRNA which is also transcribed in monocytic
      cells but does not appear to be translated. Sequence analysis of a monocyte
      derived cDNA corresponding to the type II IL-1R mRNA shows that the monocyte and
      B-cell mRNAs are identical. Comparison of monocyte IL-1R peptide maps with those
      of the type II IL-1R suggests that the two surface IL-1R are identical. This was
      confirmed serologically using a polyclonal antiserum raised against the type II
      IL-1R. Data are presented which indicate that primary human neutrophils can also
      be induced to express abundant type II IL-1R.

PMID- 1385989
TI  - Bacteriophage cloning and Escherichia coli expression of a human IgM Fab.
AB  - We have combined the molecular biology methods of the polymerase chain reaction
      and recombinant DNA cloning in bacteriophage lambda to express a human IgM Fab in
      Escherichia coli using genes derived from an Epstein-Barr virus transformed cell
      line. This method comprises three cDNA amplifications and a single cloning step,
      culminating in the stable overexpression of mammalian heterodimeric recombinant
      protein in a prokaryotic host.

PMID- 1385990
TI  - Both CD8+ and CD16+ human T cell clones can provide B cell help for
      immunoglobulin production.
AB  - The functional properties of two CD4+CD8-CD16-, five CD4-CD8+CD16- and three CD4
      CD8-CD16+ human T cell clones were compared. All CD4- T cell clones displayed
      strong cytolytic activity in the lectin-dependent lytic assay against the P815
      murine mastocytoma cell line, but only the CD4-CD8-CD16+ T cell clones exhibited
      lytic activity against the natural killer-sensitive K562 cell line. Upon
      activation with anti-CD3 monoclonal antibody, all T cell clones were able to
      support IgM and IgA synthesis in autologous B cells. Both CD4+ and CD4- T cell
      clones required cell-to-cell interaction with the B cells in order to exert their
      helper activity for immunoglobulin production. However, unlike CD4+, CD4-CD8+CD16
      and CD4-CD8-CD16+ T cell clones provided helper function for immunoglobulin
      synthesis only when low T/B cell ratios were used in culture. At higher T/B cell
      ratios, there was a decline in the B cell helper activity of CD4- T cell clones
      that was probably related to the expression of cytolytic capacity against the
      antigen-presenting B cell. These data support the notion that under certain
      experimental conditions even cytotoxic T lymphocytes and natural killer cells may
      provide B cell helper function.

PMID- 1385992
TI  - High energy collision-induced dissociation of alkali-metal ion adducts of crown
      ethers and acyclic analogs.
AB  - High energy collision-induced dissociation (CID) techniques were applied for
      structural elucidation of alkali-metal ion adducts of crown ethers. The CID of
      alkali-metal adducts of tetraglyme and hexaethylene glycol were also evaluated to
      contrast the fragmentation pathways of the cyclic ethers with those of acyclic
      analogs. A common fragmentation channel for alkali-metal ion adducts of all the
      ethers, which results in distonic radical cations, is the homolytic cleavage of
      carbon-carbon bonds. Additionally, dissociation by carbon-oxygen bond cleavages
      occurs, and these processes are analogous to the fragmentation pathways observed
      for simple protonated ethers. The proposed fragmentation pathways for alkali
      metal ion adducts of crown ethers result mostly in odd-electron, acyclic product
      ions. Dissociation of the alkali-metal ion adducts of the acyclic ethers is
      dominated by losses of various neutral species after an initial hydride or proton
      transfer. The CID processes for all ethers are independent of the alkali-metal
      ion sizes; however, the extent of dissociation of the complexes to bare alkali
      metal ions increases with the size of the metal.

PMID- 1385991
TI  - DNA sequence characterization of the G gene region of bacteriophage Mu.
AB  - The nucleotide sequence of a 1.2 kb region of bacteriophage Mu DNA was
      determined. This region contains the 3' end of the F gene, the complete G gene,
      and the 5' end of the I gene, all late genes involved in Mu virion morphogenesis.
      Identity of the G gene open reading frame was confirmed by sequencing four Gam
      mutations. The G open reading frame is predicted to encode proteins of 16.7 or
      17.2 kDa, depending on which of two possible start codons are used to initiate
      translation. Four new nuB mutations in the DNA gyrase-binding site between the G
      and I genes were also sequenced and found to be identical to the nuB103 mutation
      sequenced previously.

PMID- 1385994
TI  - Relationship of MMPI cluster type, pain coping strategy, and treatment outcome.
AB  - The purposes of the present study of chronic pain patients were to (a) assess
      whether cognitive and behavioral coping style is related to personality factors,
      (b) assess how coping styles differ across personality types, and (c) assess how
      outpatient interdisciplinary intervention affects the coping styles of various
      personality types. Four MMPI clusters (Depression/Pathological, V-type, Marginal
      Depression, and Marginal V-type) were derived using a hierarchical clustering
      procedure. Seventy subjects also completed the Coping Strategies Questionnaire
      before and after a 3-week outpatient pain management program. Pretreatment
      analyses indicated the Depression/Pathological and Marginal Depression groups
      used diverting attention less than either V-type group. The V-type group reported
      using praying/hoping significantly more than either of the marginal groups. At
      posttreatment the Depression/Pathological group used catastrophizing
      significantly more than either of the marginal groups. Results of pre-post
      analyses indicated that the Depression/Pathological group increased their use of
      diverting attention, reinterpreting pain sensations, and ignoring pain
      sensations, while decreasing catastrophizing. The V-type group increased their
      use of reinterpreting pain sensations, while decreasing praying/hoping and
      catastrophizing. Neither of the Marginal subtypes showed significant pre-post
      changes in coping strategies. These results suggest that different personality
      types use different pain coping strategies prior to multidisciplinary treatment.
      Groups showing more severe psychological distress, perhaps related to an
      underlying personality disorder, displayed greater changes in coping strategies
      with treatment, but remained more dysfunctional after treatment. These findings
      suggest that the alteration of coping strategies may be an important treatment
      effect needing more individualization to maximize treatment response.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1385993
TI  - Leukemic phase of intermediate non-Hodgkin's lymphoma with cells showing
      different matured stages in invaded various organs.
AB  - A 56-year-old male was admitted to our hospital with lymphocytosis (16.4 x
      10(9)/l; 79% lymphocytes including 50% small lymphocytes), generalized
      lymphadenopathy, massive splenomegaly, and heavily infiltrated bone marrow.
      Immunophenotype analysis of the neoplastic cells in the bone marrow revealed that
      they were B cells (CD20 + CD19 + Ia1 + sIgM+) positive for CD10. By contrast, the
      cells in the lymph node were CD20 + CD19 + Ia1 + sIgM+ but negative for CD10. The
      patient was tentatively diagnosed as having lymphosarcoma cell lymphoma, however,
      the final diagnosis was leukemic phase of intermediate lymphocytic lymphoma. We
      concluded that CD10+ neoplastic cells in the bone marrow and peripheral blood had
      differentiated to CD10- cells.

PMID- 1385996
TI  - Early detection measures and triage procedures for suicide ideation in chronic
      pain patients.
AB  - There is a dearth of writings about early detection of potential suicide patients
      in chronic pain centers. Early detection measures used at the Vanderbilt Pain
      Control Center include a Symptom Checklist-90, with questions about depressive
      symptomatology and "Thoughts of Ending Your Life"; medical and psychological
      interviews; monitoring of changes in emotional disturbance; and, if warranted,
      administration of the Scale of Suicidal Ideation. Three case studies are
      presented that indicate that the results of an assessment measure should be
      tempered with clinical judgment. Suicidal behavior, including suicidal ideation,
      is a medical emergency; therefore, there is great need for early detection and
      triage measures.

PMID- 1385995
TI  - Plasma beta-endorphin is not affected by treatment with imipramine or paroxetine
      in patients with diabetic neuropathy symptoms.
AB  - To determine the possible role of endogenous opioid peptides in the action of
      imipramine and paroxetine in painful diabetic neuropathy, beta-endorphin
      concentrations in plasma were measured in 20 patients during a double-blind,
      placebo-controlled randomized three-way crossover trial. Despite a significant
      reduction in neuropathy symptoms during both imipramine and paroxetine treatment,
      the beta-endorphin level was unaltered throughout the study. The plasma
      concentration of beta-endorphin was not related to plasma drug concentrations.
      Thus, this study does not provide evidence of a role of endogenous opioid
      peptides in the mechanism of action of imipramine and paroxetine in painful
      diabetic neuropathy.

PMID- 1385997
TI  - Cell cycle control in normal and neoplastic cells.
AB  - Recent studies of cell cycle control suggest that cyclin-dependent protein
      kinases play a central role in the cell's commitment to a new division cycle in
      late G1. The regulation of these kinases in normal and neoplastic growth is
      becoming clear.

PMID- 1385998
TI  - Ephedrine and amphetamine induced pecking in chickens: possible indirect D-1/D-2
      dopaminergic mechanism.
AB  - The involvement of dopaminergic mechanism in pecking behaviour has been
      suggested. In the present work, the involvement of D-1/D-2 dopamine receptors in
      pecking induced by ephedrine and amphetamine in chickens has been studied. Both
      ephedrine and amphetamine induced pecking in a dose-dependent manner.
      Pretreatment of animals with D-1 antagonist SCH 23390, D-2 antagonist sulpiride
      or reserpine decreased the pecking response induced by both drugs.
      Phenoxybenzamine or propranolol (alpha- or beta-adrenergic blockers,
      respectively) and the antimuscarinic drug atropine did not decrease the response
      of these drugs. The results may indicate that the pecking induced by these drugs
      in chickens are mediated indirectly through D-1/D-2 dopaminergic mechanisms.

PMID- 1385999
TI  - Effects of (R)-8-OH-DPAT and the enantiomers of UH-301 on motor activities in the
      rat: antagonism of (R)-8-OH-DPAT-induced effects.
AB  - The effects of the enantiomers of 5-fluoro-8-hydroxy-2-(dipropylamino)tetralin,
      UH-301 and the potent 5-HT1A-receptor agonist (R)-8-hydroxy-2
      (dipropylamino)tetralin, (R)-8-OH-DPAT, on locomotion, rearing and total activity
      were studied in rats. The experiments were performed as tests either of
      exploratory activity in non-habituated rats or of motor activity of rats
      habituated to the environment for 2 h before drug injection. (R)-8-OH-DPAT
      increased locomotion and total activity and decreased rearing in both conditions.
      (R)-UH-301 increased locomotion and slightly also total activity in habituated
      rats and decreased rearing in both conditions. (S)-UH-301 decreased locomotion
      and rearing in both conditions but only in doses of 10 mumol/kg and above. Lower
      doses of (S)-UH-301 (10 mumol/kg) antagonized (R)-8-OH-DPAT-induced increases of
      locomotion and total activity. As (S)-UH-301 decreased rearing, per se, it was
      not able to antagonize the (R)-8-OH-DPAT induced decrease. These results further
      support previous data that (S)-UH-301 is a 5-HT1A antagonist while (R)-UH-301 is
      a 5-HT1A agonist.

PMID- 1386001
TI  - Surgery not as wonderful as proclaimed.

PMID- 1386000
TI  - A gibberellin response complex in cereal alpha-amylase gene promoters.
AB  - The Amy32b gene is a representative member of a closely related family of alpha
      amylase genes expressed under hormonal control in aleurone layers of barley
      grains. Transcription of this gene is induced by gibberellin (GA) and suppressed
      by abscisic acid. In this study, we functionally defined the promoter elements of
      the Amy32b gene that govern the developmental and hormonal control of its
      expression in aleurone. Two functionally distinct yet physically associated
      elements are essential: a gibberellin response element mediates regulation by GA
      and abscisic acid, and an Opaque-2 binding sequence (O2S) is thought to interact
      with a barley homolog of the maize endosperm-specific transcriptional regulator
      Opaque-2. An additional element CCTTTT, which with the O2S forms part of a
      canonical "endosperm box," is important in modulating the absolute level of
      expression of the Amy32b promoter, as is another separate, highly conserved
      element TATCCATGCAGTG.

PMID- 1386002
TI  - Passive tumor targeting of soluble macromolecules and drug conjugates.
AB  - The biodistribution of soluble macromolecules is governed extensively by their
      ability to penetrate endothelial layers. Many solid tumors possess vasculature
      that is hyperpermeable to macromolecules, not always correlating with the
      presence of interendothelial cell fenestrations. The exact physiological
      mechanisms responsible for this nonspecific leakiness are not yet fully
      understood. Together with enhanced vascular permeability, however, tumors usually
      lack effective lymphatic drainage; consequently, they selectively accumulate
      circulating macromolecules (up to 10% of an i.v. dose per gram in mice). This
      "enhanced permeability and retention effect" (EPR effect) has been studied
      extensively, and it is thought to constitute the mechanism of action of SMANCS
      (styrene-maleic/anhydride-neocarzinostatin), now in regular clinical use in Japan
      for the treatment of hepatoma. It seems likely that EPR also contributes to the
      anticancer activity of the N-(2-hydroxypropyl)methacrylamide copolymer
      anthracycline conjugates which are shortly to undergo clinical evaluation in the
      U.K.

PMID- 1386003
TI  - How satisfied are parents of pre-school children who have special needs with the
      services they have received? A consumer survey.
AB  - The parents of 41 pre-school children with special needs volunteered to
      participate in a consumer survey to ascertain their satisfaction with the
      services they had received and how these could be improved. The survey produced
      an overall high level of satisfaction, although parents felt they had not
      received as much information as they wanted on their child's condition (29%),
      available help for their family (44%), financial benefits (61%), or information
      about their child's future (61%). Families also felt that they had not received
      enough family support (43%), and that professionals regularly did not understand
      their concerns (32%). Ways in which these issues could be addressed are
      discussed, along with more general issues of such consumer satisfaction surveys.

PMID- 1386004
TI  - Early social-emotional development in blind infants.
AB  - In order to study the impact of blindness on social and emotional development
      during the first year of life, the level of social-emotional development was
      compared in blind and sighted 9- and 12-month-old infants. The five 9-month-old
      and the 17 12-month-old blind infants were completely blind from birth and
      exhibited no further serious disabilities. Social-emotional development was
      assessed with a scale from the Bielefeld Developmental Test for Blind Infants and
      Preschoolers containing three subscales on emotions, social interaction and
      impulse control. Compared to non-disabled infants, blind infants exhibited a more
      limited repertoire of facial expressions and less responsiveness. They less
      frequently attempted to initiate contact with their mothers (self-initiated
      interactions) or comply with simple requests and prohibitions than sighted
      infants. These differences in the social-emotional development of blind and
      sighted infants are traced back to the effects of blindness on the mother-child
      interaction. The lack of visual perception appears to impede particularly the
      acquisition of a dialogue concept.

PMID- 1386005
TI  - Contact dermatitis in hairdressers: the Italian experience. Gruppo Italiano
      Ricerca Dermatiti da Contatto e Ambientali.
AB  - A multicenter study was performed in 9 Italian centers by members of the GIRDCA,
      to evaluate the frequency and source of contact sensitization in a group of 302
      hairdressers with dermatitis. Occupational habits and use of preventive measures
      were specifically investigated both in these 302 hairdressers and in a further
      group of 240 hairdressers who answered a questionnaire. The results showed the
      presence of an occupationally relevant sensitization in 60.9% of the 302
      hairdressers. This proportion included 52 hairdressers who had negative patch
      tests to the hairdressers' series but showed positive reactions to other
      allergens, such as nickel, rubber additives, preservatives and fragrances, which
      were judged relevant to their occupation. Among hair dyes, PPD caused 73
      reactions (24.2%), PAP 32 reactions (10.6%), ONPPD 24 reactions (7.9%), and PTD
      40 reactions (13.2%). A low incidence of sensitization was detected in our
      hairdressers to resorcinol and pyrogallol (1.3% for each substance). Among
      permanent wave allergens, positive reactions to GMTG were found in 11.3% of
      patients, while ATG gave a lower rate of positive reactions (5.0%). Allergic
      contact dermatitis due to APS was also relatively common (11.3%). 4 hairdressers
      in this study gave a positive reaction 30 min after a provocative test with latex
      gloves, patch testing to the rubber series being negative. Enquiry regarding
      preventive measures revealed that the majority of hairdressers use gloves when
      doing hair dyeing, but rarely use them for washing dyed hair or for doing
      permanent waving. The infrequent use of preventive measures by Italian
      hairdressers was confirmed by the results of the questionnaire, and possibly
      explains the high frequency of skin problems (12.5%) in the hairdressing
      population that was specifically interviewed.

PMID- 1386006
TI  - A case of budesonide contact allergy.

PMID- 1386007
TI  - Allergy to subcutaneous heparin.

PMID- 1386008
TI  - Contact dermatitis from tioconazole with cross-sensitivity to other imidazoles.

PMID- 1386009
TI  - Allergic contact dermatitis due to diazo copy paper.

PMID- 1386010
TI  - Occupational contact dermatitis due to delayed allergy to pig epithelia.

PMID- 1386011
TI  - Allergic contact dermatitis from dazomet.

PMID- 1386013
TI  - Shampoo dermatitis due to cocamidopropyl betaine.

PMID- 1386012
TI  - Contact sensitivity to the stearyl alcohol in Efudix cream (5-fluorouracil).

PMID- 1386014
TI  - Allergic contact dermatitis from MCI/MI biocide in a printer.

PMID- 1386015
TI  - Occupational dermatosis in coconut palm climbers.

PMID- 1386016
TI  - Allergic contact dermatitis from resin hardeners during the manufacture of
      thermosetting coating paints.
AB  - 5 production operators from 2 factories manufacturing thermosetting coating paint
      developed work-related skin disorders within 12 months of the introduction of a
      new powdered paint product. All 5 workers were found to have allergic contact
      dermatitis from 2 epoxy resin hardeners, both of which were commercial
      preparations of triglycidyl isocyanurate (TGIC). 2 of the workers had concomitant
      sensitization to epoxy resin in the standard series and several of the epoxy
      resin preparations at the workplace. TGIC has been reported as a contact
      sensitizer both in persons producing the chemical and among end-users of TGIC
      containing products. These 5 reported cases document allergic contact dermatitis
      from commercial TGIC among exposed workers during an intermediate process of
      powdered paint manufacture. The possibility of substituting this epoxy resin
      hardener with less sensitizing alternatives should be explored.

PMID- 1386017
TI  - Hand dermatitis in the pottery industry.
AB  - Irritant hand dermatitis has long been recognized in the pottery industry. In our
      series, among workers handling glaze, sensitization to chromate was common and
      allergy to other metals and to biocides also occurred. Allergy to oil additives
      was found in mould makers. Whilst irritant hand dermatitis does occur, allergy to
      metals and biocides should be looked for in workers handling glazes, and allergy
      to oil additives in mould makers.

PMID- 1386018
TI  - Autosomal-dominant polycystic kidney disease and hypertension: a review.

PMID- 1386019
TI  - Failure of ondansetron to block the discriminative or reinforcing stimulus
      effects of cocaine in the rat.
AB  - Ondansetron (GR38032F), a serotonin 5HT3 antagonist, is active in numerous
      behavioral paradigms and neurochemical systems. Since 5HT3 antagonists have been
      suggested as therapeutic agents for the treatment of drug abuse, the action of
      ondansetron on cocaine drug discrimination and self-administration paradigms in
      rats was investigated. Doses of ondansetron (0.001 - 1.0 mg/kg) had no effect on
      the discriminative stimulus properties of 10 mg/kg cocaine. In contrast SCH23390,
      a dopamine D1 antagonist known to block cocaine discrimination, acted as
      previously reported. Ondansetron did not augment the effects of SCH23390, but at
      higher doses, combinations of ondansetron and SCH23390 produced disruption of
      lever pressing in the presence of cocaine. Ondansetron (0.001-1.0 mg/kg) had no
      effect on the self-administration of various doses of cocaine, nor did it have
      any effect on reacquisition of cocaine self-administration in animals with a
      history of active administration followed by a period of abstinence. As before,
      SCH23390, known to block cocaine self-administration, acted as previously
      reported. Although other 5HT antagonists may prove to be efficacious in cocaine
      abuse, ondansetron appears unlikely to alter the subjective or rewarding stimulus
      properties of cocaine.

PMID- 1386020
TI  - [Subacute progressive polyneuropathy syndrome in HIV infection. The efficacy of
      immunosuppressive treatment?].
AB  - A subacute advanced severe sensorimotor polyneuropathy developed over 6 months in
      a 47-year-old patient in stage 5 of an HIV infection (Walter Reed Hospital
      classification). Clinical examination, cranial computed tomography and spinal
      nuclear magnetic imaging failed to demonstrate any central nervous system
      complication. Cerebrospinal fluid showed a lymphocytic pleocytosis of 57/3 cells
      and total protein raised to 132 mg/dl as sign of an abnormal blood-brain barrier.
      Circulating immune complex in blood was raised to 30%. Assuming an immune-complex
      mediated neuropathy treatment with oral steroids was started, initially 150 mg
      daily. The signs of polyneuropathy regressed almost completely, even after
      prednisolone was discontinued. The proportion of circulating immune complexes in
      blood fell within 7 weeks to 10% during this treatment. It is suggested that in
      HIV-infected patients severe polyneuropathies may develop as part of a humoral
      immune reaction in which immunosuppressive treatment can be effective. Even in
      advanced HIV infection high-dosage and prolonged steroid treatment can be
      undertaken, under strictest indications, and may have impressive results.

PMID- 1386021
TI  - An 88-kDa protein of Plasmodium falciparum is related to the band-3-binding
      domain of human erythrocyte ankyrin.
AB  - Three tryptic-peptide sequences of an 88-kDa pair of phosphoproteins of the
      malaria parasite Plasmodium falciparum were determined. They exhibit a striking
      similarity to corresponding sequences of the 89-kDa domain of human erythrocyte
      ankyrin. [35S]Methionine labeling of the two proteins demonstrated their
      parasitic origin. Using an appropriate oligonucleotide probe, Southern-blot
      analysis of genomic malaria DNA and Northern-blot analysis of malaria RNA suggest
      the existence of ankyrin-related sequences in the parasite genome and the
      presence of an ankyrin-related transcript of about 3.2 kb. Our studies provide
      further evidence of malaria-specific analogues of host-cell proteins, implying an
      unusual kind of parasite/host interaction.

PMID- 1386022
TI  - Cloning, sequencing and in vivo expression of genes encoding the F0 part of the
      sodium-ion-dependent ATP synthase of Propionigenium modestum in Escherichia coli.
AB  - A DNA fragment containing the genes encoding subunits of the F0 part of the
      sodium-translocating ATPase of Propionigenium modestum was cloned in Escherichia
      coli and sequenced. The predicted amino acid sequences of subunits a, b and c of
      the P. modestum ATPase were compared with those of the corresponding subunits of
      proton-translocating ATPases from other bacteria and chloroplasts. Deletion
      mutants of E. coli, lacking different genes for ATPase subunits, were transformed
      with a recombinant plasmid, containing the genes for the subunits a, c, b, delta
      and part of alpha of the ATPase of P. modestum. Functionally reconstituted ATPase
      activity could be demonstrated for the transformants. The identity of the vector
      containing P. modestum genes was verified by restriction analysis of plasmid DNA.

PMID- 1386023
TI  - Development of a mutagenesis, expression and purification system for yeast
      phosphoglycerate mutase. Investigation of the role of active-site His181.
AB  - A system has been developed to allow the convenient production, expression and
      purification of site-directed mutants of the enzyme phosphoglycerate mutase from
      Saccharomyces cerevisiae. This enzyme is well characterised; both the amino acid
      sequence and crystal structure have been determined and a reaction mechanism has
      been proposed. However, the molecular basis for catalysis remains poorly
      understood, with only circumstantial evidence for the roles of most of the active
      site residues other than His8, which is phosphorylated during the reaction cycle.
      A vector/host expression system has been designed which allows recombinant forms
      of phosphoglycerate mutase to be efficiently expressed in yeast with no
      background wild-type activity. A simple one-column purification protocol
      typically yields 30 mg pure enzyme/1 l of culture. The active-site residue,
      His181, which is thought to be involved in proton transfer during the catalytic
      cycle, has been mutated to an alanine. The resultant mutant has been purified and
      characterised. Kinetic analysis shows a large decrease (1.6 x 10(4)) in the
      catalytic efficiency, and an 11-fold increase in the Km for the cofactor 2,3
      bisphosphoglycerate. These observations are consistent with an integral role for
      His181 in the reaction mechanism of phosphoglycerate mutase, probably as a
      general acid or base.

PMID- 1386024
TI  - Determination of the sequence coding for the beta subunit of the human high
      affinity IgE receptor.
AB  - The cDNA encoding the beta subunit of the human high-affinity IgE receptor was
      cloned by a combination of various polymerase chain reactions (PCR). A major
      portion of the beta cDNA was amplified using primers homologous within the
      sequences of rat and mouse. The 3' unknown sequence was preferentially amplified
      using the RNA template-specific PCR and the improved two-step PCR. The 5' unknown
      sequence was specifically amplified by our newly developed PCR walking. Random
      heptanucleotides tagged with a unique sequence at the 5' end were used as the
      walking primer. Finally, the entire coding region was amplified and sequenced.
      The two extracellular loops of the human beta subunit were the least homologous
      to those of rat and mouse.

PMID- 1386025
TI  - Cloning and sequencing of the 23 kDa mouse photoreceptor cell-specific protein.
AB  - The 23 kDa protein was localized by immunocytochemistry to photoreceptor cells of
      the mouse retina, and bovine and mouse cDNA clones were isolated and sequenced.
      The deduced amino acid sequences showed that the mouse 23 kDa protein is 91%
      identical to the bovine protein, and is the same as S-modulin, the CAR (cancer
      associated retinopathy) protein and recoverin, the Ca(2+)-dependent activator of
      photoreceptor guanylate cyclase. The amino acid sequence reveals two Ca2+ binding
      sites, no internal repeats, 59% homology to the chicken visinin protein and 40%
      homology to calmodulin while Northern analysis demonstrated a single 1.0 kb mRNA
      species in bovine and mouse retina.

PMID- 1386026
TI  - Combinatorial RNA splicing alters the surface charge on the NMDA receptor.
AB  - Transcripts encoding four NMDA receptor subunits, generated from the NMDAR1 gene
      by alternative RNA splicing, have been demonstrated in adult rat brain. RNA
      transcripts derived from cDNAs encoding each form direct the formation of
      functional NMDA receptors in Xenopus oocytes. The two amino acid cassettes of 21
      and 37 amino acids found in the splice variants increase the positive
      extracellular surface charge on the subunits and may thereby modulate the
      functional properties of the receptor.

PMID- 1386028
TI  - Mutational analysis of the role of Glu309 in the sarcoplasmic reticulum Ca(2+)
      ATPase of frog skeletal muscle.
AB  - Site-specific mutagenesis was used to analyse the role of the residue, Glu309, in
      the function of the Ca(2+)-ATPase of frog skeletal muscle sarcoplasmic reticulum
      by substitution with Ala or Lys. At pH 6.0, 100 microM Ca2+ was unable to prevent
      phosphorylation from Pi, consistent with previous observations on the Ca(2+)
      ATPase of rabbit fast twitch muscle [Clarke, D.M., Loo, T.W, Inesi, G. and
      MacLennan, D.H. (1989) Nature 339, 476-478]. At neutral pH, however, micromolar
      concentrations of Ca2+ were sufficient to inhibit phosphorylation of the Glu309--
      -Lys mutant from inorganic phosphate, suggesting that at least one high-affinity
      Ca2+ site was relatively intact in this mutant. The Glu309----Lys mutant was
      unable to form a phosphoenzyme from ATP at all Ca2+ concentrations studied (up to
      12.5 mM), whereas phosphorylation of the Glu309----Ala mutant occurred at 12.5 mM
      Ca2+, but not at Ca2+ concentrations in the submillimolar range. Kinetic studies
      demonstrated a reduced rate of dephosphorylation of the E2P intermediate in the
      Glu309----Lys mutant. A less pronounced stabilization of E2P was observed with
      the Glu309----Ala mutant, suggesting a possible role of the charge at the
      position of Glu309 in phosphoenzyme hydrolysis.

PMID- 1386027
TI  - Deduced amino acid sequence and E1-E2 equilibrium of the sarcoplasmic reticulum
      Ca(2+)-ATPase of frog skeletal muscle. Comparison with the Ca(2+)-ATPase of
      rabbit fast twitch muscle.
AB  - The cDNA encoding a Ca(2+)-transport ATPase of frog (Rana esculenta) skeletal
      muscle was isolated and characterized. The deduced amino acid sequence,
      consisting of 994 residues, showed 89% identity to the fast twitch muscle
      sarcoplasmic reticulum Ca(2+)-ATPases of chicken and rabbit. Northern blot
      analysis using a fragment of this cDNA as probe detected a 5.0 kb message in frog
      skeletal muscle but did not detect any mRNA encoding sarcoplasmic reticulum
      Ca(2+)-ATPase in frog cardiac muscle. The enzymatic properties of the amphibian
      skeletal muscle Ca(2+)-ATPase were compared with those of the rabbit fast twitch
      muscle Ca(2+)-ATPase by functional expression of the cDNAs in COS-1 cells. The
      amphibian Ca(2+)-ATPase displayed a reduced apparent affinity for Ca2+ and an
      increased apparent affinity for the inhibitors, vanadate and thapsigargin,
      relative to the mammalian enzyme. This may be explained by a mechanism in which
      relatively more of the E2 conformation accumulated in the frog Ca(2+)-ATPase than
      in the mammalian enzyme.

PMID- 1386029
TI  - An open randomized comparative study of the effect of goserelin depot and danazol
      in the treatment of endometriosis. Zoladex Endometriosis Study Team.
AB  - OBJECTIVE: To compare the efficacy and safety of goserelin depot and danazol for
      endometriosis. DESIGN: Open, randomized comparative trial. SETTING: Multicenter
      European academic clinical institutions. PATIENTS: A total of 307 patients with
      laparoscopically diagnosed endometriosis were randomized to goserelin (n = 204)
      or danazol (n = 103); 249 patients underwent second look laparoscopy (175
      received goserelin and 74 danazol) and were analyzed for efficacy. INTERVENTIONS:
      A 3.6-mg depot of goserelin monthly subcutaneously or oral danazol 200 mg three
      times a day administered for 24 weeks. MAIN OUTCOME MEASURES: Efficacy
      assessments were based on changes in visible deposits at laparoscopy before and
      after treatment and subjective symptom scores at 4-week intervals during
      treatment and 8-week intervals after treatment for up to 24 weeks. Safety was
      assessed by adverse event reporting and clinical laboratory measures. RESULTS:
      There were similar proportions of symptomatic (73%) and asymptomatic (but
      infertile) (27%) and comparable distribution of different severity of
      endometriosis randomized to each treatment. Significantly fewer patients
      randomized to goserelin (6.4%) withdrew during treatment compared with 20.4%
      randomized to danazol (P less than 0.05). There were significantly reduced
      visible deposits of endometriosis found post-treatment (P less than 0.0001)
      within each group but no differences between the treatments. The mean total
      subjective symptoms scores remained significantly less than entry at 24 weeks
      post-treatment (P less than 0.05). Hypoestrogenic side effects were more common
      in those receiving goserelin, particularly hot flushes, but anabolic/androgenic
      side effects of weight gain and muscle cramps were more common in those receiving
      danazol. CONCLUSIONS: The monthly administered 3.6-mg depot preparation of
      goserelin was highly effective at inducing resolution of endometriotic implants
      and relieving the symptoms of endometriosis with prevention of their return
      during 24 weeks follow-up in the majority of patients. However, results were not
      significantly different from those achieved with danazol 600 mg/d.

PMID- 1386031
TI  - Evolution of spontaneous endometriosis in the baboon (Papio anubis, Papio
      cynocephalus) over a 12-month period.
AB  - To document the spontaneous evolution of endometriosis, a repeat laparoscopy was
      performed in 11 baboons after 10 and/or 12 months. The mean number of
      endometriotic lesions had increased significantly after 10 months (P less than
      0.02) because of a high proportion of new lesions (82%). These implants were
      mainly subtle (67%) and localized on the uterine peritoneum (58%). Progression of
      endometriosis did not go beyond revised AFS stage I. Additionally, repeat
      laparoscopy in 10 baboons with an initially normal pelvis showed an endometriosis
      incidence of 70% after 10 to 12 months. Remodeling of the lesions was apparent in
      both groups after 12 months. These results suggest that endometriosis is
      moderately progressive in the baboon. It is possible that multiple laparoscopies
      could favor the development of endometriosis.

PMID- 1386030
TI  - Direct effects of medroxyprogesterone acetate, danazol, and leuprolide acetate on
      endometrial stromal cell proliferation in vitro.
AB  - OBJECTIVE: To assess the direct effects of three endometriosis chemotherapeutic
      agents (medroxyprogesterone acetate [MPA], danazol, and leuprolide acetate [LA])
      on endometrial cell proliferation. DESIGN: Analysis of cell proliferation in
      vitro. SETTING: Proliferative phase endometrial stromal cells isolated from
      biopsy specimens and grown in short-term culture served as a model for stromal
      components of endometriotic implants. PATIENTS: Biopsies obtained from volunteers
      with regular cycles and without endometriosis or endometrial pathology.
      INTERVENTIONS: Medroxyprogesterone acetate, danazol, and LA were added to
      nutrient media with the following supplements: 2.5% calf serum (CS) only; 2.5%
      CS+estradiol (E2) 110 pmol/L; 2.5% CS+E2 550 pmol/L; 10% preovulatory serum (net
      E2 624 pmol/L). MAIN OUTCOME MEASURES: Cumulative [3H]-thymidine incorporation as
      a reflection of cell proliferation. RESULTS: Medroxyprogesterone acetate and
      danazol exerted significant antiproliferative effects on stromal cell
      proliferation (P less than 0.05), effects that were enhanced by an absence of
      exogenous E2. Leuprolide acetate exerted no consistent effects. CONCLUSIONS:
      These data imply that MPA and danazol but not LA exert direct effects,
      suppressing growth of endometriotic implants.

PMID- 1386032
TI  - Laparoscopic CO2 laser uterine nerve ablation for treatment of drug resistant
      primary dysmenorrhea.
AB  - Twenty women with drug-resistant primary dysmenorrhea were subjected to
      laparoscopic CO2 laser uterine nerve ablation. Menstrual pain assessed by a
      linear analog pain score showed a reduction of 33%, decreasing from 7.5 +/- 0.5
      preoperatively to 5.0 +/- 1.7 postoperatively. The procedure was free of major
      complications and should be considered as a second-line therapeutic option in
      women who have failed medical treatment using nonsteroidal antiinflammatory
      agents or OCs.

PMID- 1386033
TI  - Application of the cavitron ultrasonic surgical aspirator (CUSA) for
      gynecological laparoscopic surgery using the rabbit as an animal model.
AB  - OBJECTIVE: To study the potential application of the cavitron ultrasonic surgical
      aspirator (CUSA) in gynecological laparoscopic surgery using a rabbit animal
      model. DESIGN: Twenty-six rabbits were prospectively randomized into two groups.
      Laparoscopically directed standard injuries were made on the randomly assigned
      horn and sidewall in all animals with the CUSA. Contralateral injuries were made
      with a contact neodymium-yttrium aluminum garnet (Nd:YAG) laser in group 1 and
      with bipolar cautery in group 2. Adhesion and inflammation scores were assessed
      for two animals in each group at 24, 48, and 72 hours, and seven animals in each
      group at 14 days. SETTING: University animal research facility. MAIN OUTCOME
      MEASURES: Adhesion and inflammation scores were compared between animals in the
      CUSA versus Nd:YAG study and the CUSA versus bipolar cautery at 14 days. RESULTS:
      No significant difference in uterine or sidewall adhesion scores was noted
      between the CUSA versus Nd:YAG or the CUSA versus bipolar cautery. Bipolar
      cautery produced significantly less inflammation on the uterine horn compared
      with the CUSA (3.0 +/- 0.2 versus 5.3 +/- 0.7, P = 0.0001), but no difference in
      sidewall inflammation was noted between the CUSA compared with bipolar cautery.
      No difference in inflammation was observed between the CUSA and the Nd:YAG laser.
      CONCLUSIONS: The bipolar cautery appears to be preferable to the CUSA for
      coagulation of uterine lesions, although dissection of the uterus is not possible
      with bipolar cautery. The CUSA and the Nd:YAG appear to be comparable for uterine
      horn dissection. Because the CUSA causes similar adhesion formation and tissue
      inflammation at the sidewall when compared with the Nd:YAG laser and bipolar
      cautery and may be less likely to damage blood vessels, ureters, or other
      collagen-rich tissues, the CUSA may represent a promising new surgical tool for
      laparoscopically directed peritoneal dissection.

PMID- 1386034
TI  - Nafarelin versus danazol versus surgery.

PMID- 1386036
TI  - CD45: a transmembrane protein tyrosine phosphatase involved in the transduction
      of antigenic signals.

PMID- 1386035
TI  - Studies on the structure and function of D2-dopamine receptors.

PMID- 1386037
TI  - Regulation and structure-function relationship of CD45.

PMID- 1386038
TI  - CD45 regulates TCR-induced signalling through tyrosine phosphorylation of
      phospholipase C gamma 1.

PMID- 1386039
TI  - Probing the molecular architecture of (1,3)-beta-glucan (callose) synthase:
      polypeptide depletion studies.

PMID- 1386041
TI  - Subsets of CD4+ T cells defined by their expression of different isoforms of the
      leucocyte-common antigen, CD45.

PMID- 1386040
TI  - Functional subsets of T cells defined by isoforms of CD45.

PMID- 1386042
TI  - The cyclic expression of CD45R isoforms on CD4 T cells.

PMID- 1386043
TI  - Copy number of the U7 gene in some mammalian species.

PMID- 1386044
TI  - Uncoupler-induced ATPase activity of plant mitochondria.

PMID- 1386045
TI  - ABA-regulated gene expression: cis-acting sequences and trans-acting factors.

PMID- 1386046
TI  - Presymptomatic testing for late-onset genetic disorders: lessons from
      Huntington's disease.
AB  - Huntington's disease is an inherited, neurodegenerative disorder, usually of
      adult onset. Since the identification of linked markers, more than 1000
      presymptomatic tests have been performed worldwide and multiple ethical issues
      have been encountered in relation to informed consent, testing of children,
      exclusion testing during pregnancy, and confidentiality. Further ethical problems
      are anticipated after identification of the causal mutation (or mutations). As
      Huntington's disease is a model for other disorders of adult onset for which
      testing is becoming possible, the successful resolution of these ethical issues
      is of great importance. A failure to do so might discredit genetic testing as a
      whole.

PMID- 1386047
TI  - The Tiresias complex: Huntington's disease as a paradigm of testing for late
      onset disorders.
AB  - Huntington's disease represents the first disorder for which positional cloning
      techniques successfully localized an autosomal gene--in 1983. Events since that
      time have proved the gene recalcitrant to identification and characterization.
      Since 1986, presymptomatic and prenatal testing for Huntington's disease has been
      available internationally, although on a limited basis. Testing for Huntington's
      disease provides an excellent model for designing service programs for genetic
      testing for late-onset, fatal disorders, particularly when the gene is not yet in
      hand and no therapeutic intervention is possible. Special training and
      precautions must be in place before presymptomatic genetic testing should be
      offered.

PMID- 1386048
TI  - Response to hepatitis B vaccine of persons positive for antibody to hepatitis B
      core antigen.
AB  - The significance of antibody to hepatitis B core antigen (anti-HBc) present in a
      person's serum without hepatitis B surface antigen (HBsAg) or its antibody (anti
      HBs) is unknown. Serum specimens from 281 persons initially positive only for
      anti-HBc by enzyme immunoassay (EIA) were retested by radioimmunoassay (RIA), and
      of these, 177 (63%) remained positive for anti-HBc by both assays. Of these 177
      persons, 3 were positive for HBsAg, and 72 possessed low levels of anti-HBs [less
      than 10 sample ratio units; (SRU's)]. When persons positive for anti-HBc by EIA
      and RIA were given one 20-micrograms dose of plasma-derived hepatitis B vaccine
      and tested for anti-HBs 1 month later, a booster response was observed in 14 of
      41 (34%) persons with low level anti-HBs and 3 of 50 (6%) persons negative for
      anti-HBs. Of those positive only for anti-HBc by EIA but negative by RIA, only 3
      of 37 (8.1%) showed a booster response. Of those who completed the three-dose
      immunization series and did not show a booster response, 63 of 80 (78.8%)
      developed anti-HBs levels greater than 10 standard ratio unit. The majority of
      persons with isolated anti-HBc will have a primary rather than a booster response
      to hepatitis B vaccine.

PMID- 1386049
TI  - Hemodynamic, neurohumoral, and metabolic responses to amino acid infusion in
      patients with cirrhosis.
AB  - In patients with cirrhosis the renal response to amino acid infusion is
      controversial. In addition, the renal and systemic metabolic effects of amino
      acids are unknown. Therefore, the present study examined the effects of amino
      acids on renal hemodynamics, renal and systemic oxygen (O2) consumption, and
      hormones in patients with cirrhosis. Twelve patients received an 8% amino acid
      solution for 30 minutes at a rate providing 250 mg of amino acids/kg body wt.
      Renal blood flow increased by 45% (P less than 0.05) and the glomerular
      filtration rate by only 9% (P greater than 0.05). Renal vascular resistance
      decreased by 23% (P less than 0.05), and renal perfusion pressure did not change
      significantly. Renal and systemic O2 consumption and pulmonary artery plasma
      glucagon level significantly increased. There were no significant changes in
      plasma osmolality, plasma volume, and plasma atrial natriuretic peptide
      concentrations. In conclusion, the results show that amino acid-induced renal
      vasodilation caused hyperperfusion but not renal hyperfiltration in patients with
      cirrhosis. In addition, renal hyperemia was associated with renal and systemic
      hypermetabolism.

PMID- 1386050
TI  - Immunosuppressive properties of chenodeoxycholic and ursodeoxycholic acids in the
      mouse.
AB  - Cell-mediated immunity is impaired during cholestasis, and there is evidence that
      bile acids play a role in this immune defect. Ursodeoxycholic acid (UDCA), which
      corrects the immunological abnormalities observed in primary biliary cirrhosis,
      could counter the detrimental effects of the endogenous bile acids. Accordingly,
      we assessed the respective effects of cholestasis, chenodeoxycholic acid (CDCA),
      and UDCA, using mixed lymphocyte culture as a model of allogeneic immune
      response. CDCA induced a dose-dependent inhibition of the proliferative response
      (0-150 mumol/L). Mononuclear cells obtained from bile duct-ligated mice had a
      normal immunostimulatory effect, whereas responder cells obtained from such
      animals showed a profoundly impaired proliferative response, suggesting that
      responder T cels are the main target of the cholestasis-induced immune defect.
      Supplementation of cultures with exogenous interleukins partially compensated for
      the inhibitory effect of 25 mumol/L CDCA, but not for that of 50 mumol/L CDCA,
      suggesting that impaired secretion of interleukins is not the only factor
      involved in the effect of bile acids. In contrast to CDCA, UDCA had no inhibitory
      effect on the allogenic immune response at concentrations of up to 50 mumol/L.

PMID- 1386052
TI  - Selective accumulation of endogenously produced porphyrins in a liver metastasis
      model in rats.
AB  - The possibility of using the porphyrin precursor 5-aminolevulinic acid to cause
      selective porphyrin accumulation in tumors was examined. Syngeneic colon
      carcinomas CC531 were implanted in the livers of Wag/Rij rats. Groups of three to
      six animals each were given 2 mg/mL of 5-aminolevulinic acid in drinking water
      from the 8th, 14th, or 17th day after tumor implantation. Two other groups
      received either 2.5 or 5 mg/kg of Photofrin II (Photomedica Inc., Raritan, NJ)
      intravenously on day 17. On day 19 the livers were removed and porphyrin
      concentrations were measured in normal livers and tumors by solvent extraction
      and high-performance liquid chromatography. Protoporphyrin accumulated
      progressively in tumors with increasing duration of 5-aminolevulinic acid
      administration (P = 0.0001), whereas no increase was found in normal livers.
      After 11 days of 5-aminolevulinic acid administration the porphyrin concentration
      ratio between tumors and livers was 4:1. In contrast, after Photofrin II
      administration the concentration was higher in normal livers than in tumors (1:3
      ratio, tumor to liver). Enzyme measurements showed a threefold decrease in
      ferrochelatase activity in tumors compared with livers (P less than 0.001). In
      conclusion, oral administration of 5-aminolevulinic acid results in progressive
      accumulation of protoporphyrin in a transplantable colon carcinoma without
      accumulation in the surrounding liver tissue. This selective accumulation of
      porphyrins appears to be caused by a relative ferrochelatase deficiency in
      malignant tissue. 5-Aminolevulinic acid administration may be a suitable approach
      to photosensitizing liver tumors for photodynamic therapy or to early detection
      of tumors by fluorescence in ultraviolet light.

PMID- 1386051
TI  - Evidence for a storage pool defect in platelets from cirrhotic patients with
      defective aggregation.
AB  - The mechanisms underlying the defective platelet function in cirrhotic patients
      were investigated. Eleven cirrhotic patients with mild disease (group 1), 20
      patients with severe cirrhosis (group 2), and 31 controls were studied. Platelet
      aggregation was significantly reduced in cirrhotics compared with controls.
      Compared with controls, cirrhotic patients in group 2 showed a significant
      reduction in the total content of adenosine triphosphate (57.8 +/- 7.8 vs. 26.1
      +/- 6.3 mumol/10(11) platelets; P less than 0.05), 5-hydroxytryptamine (285 +/-
      26 vs. 104 +/- 38 nmol/10(11) platelets; P less than 0.05), beta-thromboglobulin
      (2129 +/- 120 vs. 1223 +/- 161 ng/10(8) platelets; P less than 0.01), and
      platelet factor 4 (1389 +/- 108 vs. 805 +/- 176 ng/10(8) platelets; P less than
      0.05). In patients with severe disease, an increase in plasma beta
      thromboglobulin-platelet factor 4 ratio, an index of in vivo platelet activation,
      was observed (controls, 3.50 +/- 0.50; group 1, 4.02 +/- 0.80; and group 2, 6.59
      +/- 1.15). Our data indicate the existence of a platelet storage pool defect,
      which may favor the bleeding tendency of cirrhotic patients.

PMID- 1386053
TI  - [Pelviscopic salpingectomy in ruptured extrauterine pregnancy using an automatic
      stapler-incision instrument].
AB  - The case report presented describes pelviscopic salpingectomy with ruptured tubal
      pregnancy carried out by an automatic stapling and cutting instrument. This
      instrument (EndoGIA 30) was developed for endoscopic intestinal surgery by the
      Autosuture company. It can be inserted via a 12 mm trocar and allows threefold
      clip suture of 3.3 cm length on each side of the automatically cut tissue. The
      clip suture is absolutely blood dry and does not pull anatomic structures out of
      shape. Unfortunately, the instrument is available for single use only and thus
      more expensive than the traditional "Semm's three-ligature method" (1979).
      Nevertheless, it will add an improvement to minimal invasive surgery. One of the
      indication for its use is to avoid laparotomy in individual cases.

PMID- 1386054
TI  - Rat mitochondrial coupling factor 6: molecular cloning of a cDNA encoding the
      imported precursor.
AB  - A cDNA clone encoding the precursor to the rat mitochondrial protein coupling
      factor 6 (F6) has been isolated and sequenced. The deduced amino acid sequence of
      the rat precursor protein shows 78% and 74% identity with the human and bovine F6
      pre-proteins, respectively.

PMID- 1386055
TI  - Determination of hormonal response in uterine cancer cell lines by the ATP
      bioluminescence assay and flow cytometry.
AB  - Although progesterone receptor status has been shown to correlate with response
      to hormonal therapy, not all progesterone receptor-positive patients respond to
      this treatment and additional biologic assays are needed to help better predict
      clinical response to hormonal therapy. This study explored the potential of the
      ATP bioluminescence assay and flow cytometry as biological assays of hormonal
      response. Five uterine cancer cell lines were used: AE7, ECC-1, HEC1A, AN3, and
      SKUT1B. Cells were exposed to Provera or tamoxifen at 0.1, 0.2, 0.5, 1, 2, and 5X
      (X equal to peak plasma concentrations: 1.0 micrograms/ml Provera and 0.1
      micrograms/ml tamoxifen). For correlation, estrogen and progesterone receptors
      were determined by the standard dextran-coated charcoal method. Only AE7 and ECC
      1 were positive for progesterone receptors (501 fmol/mg AE7, 194 fmol/mg ECC-1)
      and the rest were negative (less than 8 fmol/mg). Tamoxifen exerted no inhibition
      to the above cell lines. Meanwhile, Provera exerted dose-response inhibition on
      both AE7 and ECC-1 cell lines. The effects of accumulation of G0-G1 phase and
      reduction of S, G2 cells (P less than 0.05), but not on the HEC1A cell line (P =
      0.4). These changes confirmed the antiproliferative property of Provera. Further
      studies are needed to establish the role of the ATP bioluminescence assay and
      flow cytometry as biological assays of hormonal response.

PMID- 1386056
TI  - [Extragenital endometriosis with multiple stenoses of the small intestine].
AB  - This paper reports on the case of a 38-year-old woman with multiple stenoses in
      the proximal and middle section of the jejunum, as well as in the terminal ileum,
      who had been symptomatic for nine years, with symptoms progressively reflecting
      obstruction due to mechanical subileus. The cause was found to be extragenital
      endometriosis which, with the mucosa remaining intact, was associated with
      hormone-dependent bleeding with subsequent fibrosis leading to segmental
      thickening of the bowel wall and narrowing of the lumen. The diagnostic work-up
      included a radiological study of the small bowel as described by Sellingk,
      abdominal sonography and a CT exam; the X-ray study and the CT scan revealed
      stenosing of the bowel, while sonography and CT showed wall thickening. The
      treatment of this condition comprises resection of the affected bowel segment
      together with anti-estrogen treatment or ovariectomy, and in this respect differs
      notable from the more common Crohn's disease of the small bowel, from which it
      must be diagnostically differentiated.

PMID- 1386057
TI  - Low-pressure balloon angioplasty of an occluded portacaval shunt.
AB  - Safe angioplasty of a portacaval shunt requires particular knowledge of the
      tissue characteristics of an anastomosis and the behavior of a balloon during
      inflation. The nature and true diameter of a portacaval shunt anastomosis are
      more difficult to evaluate than those of a peripheral arterial lesion, and
      complications are potentially more hazardous than those related to peripheral
      arterial angioplasty. We suggest that in some instances low pressure and
      incomplete balloon inflation are all that is necessary to yield safe and
      satisfactory results.

PMID- 1386058
TI  - Increased expression of 5q31 fragile site in a Bloom syndrome family.
AB  - In this work, we report spontaneous chromosomal breakpoints and fragile site
      expression induced by 5-fluorodeoxyuridine (FdUrd) and FdUrd plus caffeine in a
      family with Bloom's syndrome (BS) and 2 healthy donors. Standard and G-banded
      metaphases from each individual and each treatment were analyzed. Among the 59
      common fragile sites (c-fra) identified in this work, only the frequency of 5q31
      was significantly increased in the BS family with respect to healthy donors (P
      less than 0.005). A remarkable coincidence between the breakpoints involved in
      spontaneous chromosome aberrations and induced c-fra was found in BS homozygote
      patients. The importance of the interaction between fragile sites and chromosome
      rearrangements in cancer is discussed.

PMID- 1386059
TI  - Human T cells expressing V beta 8 do not predominantly recognize DR2 alloantigen.
AB  - A panel of seven monoclonal antibodies recognizing human T-cell antigen receptor
      (TcR) V alpha or V beta subsets has been used to measure TcR gene expression in
      peripheral blood lymphocytes and mixed lymphocyte culture responses (MLR) between
      DR2- and DR2+ (DRw15+) donors. There were no significant differences between DR2-
      and DR2+ donors in per cent T cells in fresh peripheral blood labelled with any
      of these antibodies, which included an antibody recognizing V beta 8. This
      indicates strongly that increased negative selection of V beta 8+ T cells does
      not occur in DR2+ compared with DR2- individuals. In MLR between DR2- and DR2+
      donors the only significant change compared with fresh peripheral lymphocytes was
      that T cells expressing V beta 5.1 were decreased in DR2- lymphocyte populations
      responding to DR2 alloantigen. No changes in levels of V beta 8+ T cells were
      detected in MLR between DR2- and DR2+ donors. This suggests that V beta 8+ T
      cells are not predominantly reactive against DR2 (DRw15). The data support the
      concept that alloreactivity against a single class II major histocompatibility
      complex (MHC) mismatch is mediated by T cells expressing a range of different TcR
      V beta molecules.

PMID- 1386060
TI  - Characterization of the progeny of precursor-T (pre-T) cells maintained in vitro
      by interleukin-3 (IL-3). Development of T-cell function in vivo.
AB  - We have recently described a bone marrow culture system which is able to maintain
      a portion of the precursor-T (pre-T) cell compartment of adult murine marrow in
      vitro, in the presence of interleukin-3 (IL-3), for at least 2 weeks. However,
      because growth in IL-3 might also induce the differentiation of the pre-T cells,
      it is necessary to determine the extent to which the developmental potential of
      the pre-T cells is altered during their residency in vitro. Previously, we
      analysed the progeny of cultured pre-T cells and compared their intrathymic
      development, their appearance in the periphery, and their V beta gene utilization
      to that of the progeny of fresh pre-T cells. Within these parameters, the cells
      derived from cultured marrow cells did not differ significantly from cells
      derived from fresh marrow cells. However, these studies did not allow us to
      determine the functional status of the T-cell progeny of cultured marrow. In the
      work presented here, we analysed the functional potential of T cells which were
      derived either from fresh pre-T cells or pre-T cells which had been maintained
      for 1 week in vitro. The T-cell mediated functions analysed included mitogen- and
      alloantigen-induced proliferation, IL-2 production, and generation of cytotoxic T
      cells. We found that the cultured pre-T cells were capable of giving rise to
      mature, immunocompetent T cells which did not differ significantly from the
      progeny of fresh pre-T cells in their functional potential.

PMID- 1386061
TI  - The influence of PACS on quality at the clinical level.

PMID- 1386062
TI  - Hypomelanosis of Ito associated with palmoplantar keratoderma and normal magnetic
      resonance imaging findings.

PMID- 1386063
TI  - An efficacy trial of a mammalian cell-derived recombinant DNA hepatitis B vaccine
      in infants born to mothers positive for HBsAg, in Shanghai, China.
AB  - We conducted a randomized, double-blind clinical trial of an experimental
      mammalian cell-derived DNA hepatitis B vaccine (Betagen, Connaught Laboratories
      Ltd, Toronto, Canada) to determine its efficacy in infants born to mothers who
      were carriers of hepatitis B surface antigen (HBsAg). Four groups of 55 infants
      received injections as follows: (1) a licensed plasma-derived vaccine (Lanzhou,
      Lanzhou Institute for Biological Products, Lanzhou, People's Republic of China),
      20 micrograms; (2) Betagen, 20 micrograms; (3) Betagen, 20 micrograms+hepatitis B
      immune globulin (HBIG); and (4) Betagen, 10 micrograms+HBIG. Vaccine injections
      were given at birth and at 1 and 6 months and HBIG was given at birth. The
      vaccines were compared to a historical placebo control group. The efficacy of
      Betagen alone was 82.6% compared to 51.0% for the Lanzhou. Efficacy of Betagen
      increased with the concomitant use of HBIG. No infants who were HBsAg negative at
      birth and/or were born to hepatitis B e antigen (HBeAg) negative mothers became
      carriers. The rate of HBsAg in infants receiving Betagen alone, and born to
      mothers who were HBeAg positive, decreased from 60% at birth to 20% by the ninth
      month, compared to 62.5% and 50% (respectively) for Lanzhou. The percentage of
      infants with protective levels of antiHBs was significantly higher for Betagen
      alone than for Lanzhou, but the geometric mean titre of antiHBs for responders
      was not significantly different. We have shown that Betagen alone is highly
      efficacious in preventing the development of hepatitis B in infants born to
      mothers who are carriers of HBsAg and is also highly effective in reducing the
      carriage of HBsAg in infants who are HBsAg positive at birth and/or born to HBeAg
      positive mothers.

PMID- 1386064
TI  - Reliability and validity of self and proxy reporting of morbidity data: a case
      study from Beirut, Lebanon.
AB  - We compared the self-reported illnesses (heart disease, back pain, rheumatoid
      arthritis, hypertension, and pulmonary disease) and smoking histories of 100
      cases and 100 controls matched for age and sex with reports of this information
      from proxy informants from the same household in two areas in the city of Beirut.
      In addition, both cases and controls were given physical examinations to evaluate
      the accuracy of the responses. The level of agreement between the responses of
      subjects and of their informants varied from one condition to the other. Heart
      disease had the highest level of agreement, with the proportion of agreement
      greater than 93% for the cases and the controls and having chi values of 0.79 and
      1.0, respectively. The report of back pain exhibited the lowest level of
      agreement, with responses showing a proportion of agreement of 74% for the cases
      and 90% for the controls, with chi values of 0.49 and 0.50, respectively. In
      comparing the responses of subjects and proxy informants with the results of
      physical examinations, heart disease had the highest level of agreement (J index
      ranged from 0.69 to 0.84), and back pain had the lowest level of agreement (J
      index ranged 0.42 to 0.48). These results show that proxy informants are good
      respondents for members of the same household and that health interview surveys
      are accurate for data collection of well defined chronic conditions.

PMID- 1386065
TI  - Retinal development in very-low-birth-weight infants fed diets differing in omega
      3 fatty acids.
AB  - Full-field electroretinograms (ERGs) were obtained from very-low-birth-weight
      (VLBW) neonates to determine whether omega-3 (omega-3) fatty acids are essential
      for normal human retinal development. Eighty-one infants born at 30.4 (standard
      deviation, +/- 1.5) wk gestation were, within 10 d of birth, either enrolled to
      receive mother's milk (naturally containing both omega-6 and omega-3 essential
      fatty acids) or randomized to receive one of the infant formulas. Corn oil-based
      Formula A contained mainly linoleic acid (18:2 omega-6) and was low in all omega
      3 fatty acids. Soy oil-based Formula B contained ample alpha-linolenic acid (18:3
      omega-3) but no long-chain omega-3. Formula C, supplemented with both alpha
      linolenic acid and marine oils, was comparable to human milk in long-chain omega
      3. Full-field ERGs were obtained in the special care nursery from infants aged 36
      and 57 wk postconception. Ten healthy preterm infants born at 35 wk gestation
      were tested at 36 wk postconception. Significant differences were found among
      groups in rod ERG function. Post hoc comparisons showed that infants fed Formula
      A had significantly higher rod thresholds than infants receiving long-chain omega
      3 (human milk, Formula C, and intrauterine). Infants receiving Formula B had
      intermediate thresholds that were significantly higher than those of infants
      receiving intrauterine nutrition. Analysis of the leading edge of the a-wave
      showed that b-wave differences originated at the photoreceptor level. Differences
      were not present in infants at 57 wk postconception. No significant differences
      among groups were found in cone b-waves at 36 or 57 wk postconception.
      Oscillatory potentials had significantly longer implicit times at 57 wk
      postconception in infants fed Formula A than in infants receiving human milk.
      These findings suggest that retinal function varies with the dietary supply of
      omega-3 fatty acids in VLBW infants.

PMID- 1386066
TI  - Epidermal growth factor stimulates corneal epithelial cell attachment to
      fibronectin through a fibronectin receptor system.
AB  - Epidermal growth factor (EGF) stimulates corneal epithelial migration in vivo and
      in vitro. Antibody against fibronectin inhibits this effect in vitro, suggesting
      that a fibronectin-dependent mechanism in involved. To elucidate the action of
      EGF, we placed rabbit corneal epithelial cells, preincubated in the absence or
      presence of EGF (10 ng/ml), into wells coated with fibronectin. After 45 minutes
      of incubation, the numbers of cells attached to the wells were counted.
      Preincubation with EGF for 6 hr was not effective, but preincubation for 9 hr
      significantly increased the numbers of cells attached to the wells. These numbers
      were not increased further by additional preincubation. When concentrations of
      EGF were reduced, numbers of attached cells decreased proportionally, but
      remained significantly higher than the numbers obtained with cells not exposed to
      EGF. The EGF-stimulated attachment to the fibronectin matrix was inhibited in a
      dose-dependent fashion by antifibronectin IgG and by GRGDSP, a synthetic peptide
      that mimics the amino acid sequence of the cell-binding domain of fibronectin.
      The authors conclude that a fibronectin/fibronectin receptor system mediates EGF
      induced stimulation of cellular attachment. These findings suggest that EGF may
      increase the expression of fibronectin receptors.

PMID- 1386067
TI  - Tertiary myotubes in postnatal growing pig muscle detected by their myosin
      isoform composition.
AB  - The postnatal development of skeletal muscles was studied in growing pigs from 8
      to 210 d of age. Indirect immunoperoxidase staining of frozen sections of porcine
      semimembranosus muscle and longissimus muscle revealed a distinct population of
      small fibers (tertiary myotubes) that were stained specifically by an antibody
      (anti-NE) selective for the developmental (embryonic and neonatal) isoforms of
      muscle myosin. At 8 d of age the other larger fibers were already anti-NE
      negative and differentiated into Types I and II. A gradual decrease in the number
      of anti-NE positive fibers together with a gradual increase in area of the
      remaining positive fibers was observed throughout the pigs' growth. These results
      may indicate that hyperplastic growth does not cease at birth. Possible
      mechanisms to explain the origin of these tertiary myotubes containing
      developmental isoforms of myosin are suggested.

PMID- 1386068
TI  - Promoting interaction during sociodramatic play: teaching scripts to typical
      preschoolers and classmates with disabilities.
AB  - We investigated the effects of teaching sociodramatic scripts on subsequent
      interaction among three triads, each containing 2 typical children and 1 child
      with autistic characteristics. The same type and rate of teacher prompts were
      implemented throughout structured play observations to avoid the confounding
      effects of script training and teacher prompting. After learning the scripts, all
      children demonstrated more frequent theme-related social behavior. These
      improvements in social-communicative interaction were replicated with the
      training of three sociodramatic scripts (i.e., pet shop, carnival, magic show)
      according to a multiple baseline design. These effects were maintained during the
      training of successive scripts and when the triads were reconstituted to include
      new but similarly trained partners. Results provided support for the inclusion of
      systematic training of scripts to enhance interaction among children with and
      without disabilities during sociodramatic play.

PMID- 1386069
TI  - Fading teacher prompts from peer-initiation interventions for young children with
      disabilities.
AB  - This study examined a system for fading teacher prompts to children who served as
      peers in peer-initiation interventions for young children with disabilities. A
      teacher taught peers to direct social initiations to children with disabilities,
      provided verbal prompts for those initiations, and introduced a system that
      provided peers with visual feedback about the social interactions of the children
      with disabilities. She then systematically withdrew the verbal prompts to peers,
      and subsequently faded the visual feedback system. Peer initiations increased
      when the intervention began and resulted in increases in social interaction for
      the children with disabilities. As the teacher systematically faded the prompts
      and visual feedback to the peers, social interaction continued at the levels
      found during intervention and was maintained during a short maintenance period.

PMID- 1386070
TI  - Training supervisors in a collaborative team approach to promote peer interaction
      of children with disabilities in integrated preschools.
AB  - Three supervisors of integrated preschools were trained in a collaborative team
      approach to encourage resource and classroom teachers to develop strategies that
      promote peer interaction of all children, including children with disabilities.
      The focus of classroom teachers' behaviors and the interactive play of children
      with disabilities were measured daily in both a training (indoor play period) and
      a generalization (outdoor play period) setting. In a multiple baseline design,
      supervisors were individually trained in a collaborative team approach using a
      manual, modeling, and role playing; then they implemented the approach with
      classroom and resource teachers. We found that after supervisor training,
      classroom teachers increased their behaviors directed towards children with
      disabilities and decreased their behaviors directed towards nondisabled children.
      Moreover, we found a doubling of the interactive play of children with
      disabilities and, for two of the three classes, an increase in the interactive
      play of comparison children, randomly selected by the classroom teachers. Changes
      in both teachers' and children's behaviors were also found in the generalization
      setting. The implications of the results for interventions in community settings
      are discussed.

PMID- 1386071
TI  - Treatment of acute wheezing and dyspnea attacks in children under 2 years old:
      inhalation of fenoterol plus ipratropium bromide versus fenoterol.
AB  - Two treatment regimens for the initial treatment of acute wheezing were evaluated
      in 61 wheezing infants. Thirty-one patients received fenoterol (F) (0.1 mg/kg)
      and placebo (P) and 30 patients received fenoterol (F) (0.1 mg/kg) plus a fixed
      dose of ipratropium bromide (IB) (50 micrograms). Both groups received the drugs
      by inhalation using an ultrasonic nebulizer and face mask. A clinical score
      system based on wheezing and rib cage retraction was established and evaluations
      were performed before and at 15, 30, and 45 minutes after treatment. After the
      last evaluation based on the clinical score, it was decided whether to repeat or
      not to repeat the treatment. Our results showed that a combination of a beta
      agonist and ipratropium bromide (FB) was more effective than a beta agonist alone
      (F) in reducing wheezing and dyspnea during an acute attack (63.4 versus 25.8%; p
      less than 0.05).

PMID- 1386072
TI  - Brief report: therapeutic manipulations in severe nocturnal asthma. A
      nonconventional approach in a severe high-risk asthmatic.
AB  - A patient with severe nocturnal asthma of multifactorial pathogenesis with high
      risk features leading to several episodes of nocturnal respiratory arrests is
      described. Despite aggressive conventional therapy with bronchodilators and
      glucocorticoid agents, the patient had progressive worsening within the year
      prior to admission. After a nonconventional approach consisting of: high-dose
      inhaled steroids, afternoon dose of prednisone, addition of troleandomycin
      therapy, high-dose inhaled ipratropium at bedtime, maximizing serum theophylline
      concentrations in the early morning, and nasal CPAP through the night; the
      patient's pulmonary functions were optimized with minimal or no reduction in
      morning FEV1, and decreased airways hyperresponsiveness to methacholine.

PMID- 1386073
TI  - Measurement of left ventricular mass.

PMID- 1386074
TI  - Left ventricular mass by M-mode echocardiography.
AB  - A comparison of various M-mode echocardiographic methods for assessment of left
      ventricular mass (LVM) was done in 21 subjects. The anatomical LVM was taken as
      Standard; it varied from 64.55 to 341.82 g. Of the six different M-mode echo
      methods compared, the method of Devereux and Reichek (1977) was found to
      correlate best with anatomical LVM (r = 0.99; SD = 49.54). By this method LVM =
      1.4 [(LVIDd + LVPWTd + IVSTd)3 - (LVIDd)3] - 14 g.

PMID- 1386075
TI  - Left ventricular muscle mass by echocardiography: methodology.
AB  - The limitations of electrocardiography for diagnosing left ventricular
      hypertrophy (LVH), due to unacceptable accuracy and lack of serial
      quantifications, are well known. The use of angiocardiography for LVH assessment
      is invasive, hazardous and costly. Echocardiography provides an excellent method
      of estimation of left ventricular muscle mass, which is simple, non-hazardous,
      accurate and reproducible.

PMID- 1386076
TI  - Evidence for GTP-binding protein involvement in the tyrosine phosphorylation of
      the T cell receptor zeta chain.
AB  - The zeta subunit of the T cell receptor (TCR) is a prominent substrate for a TCR
      activated tyrosine kinase. Tyrosine phosphorylation of the zeta subunit in
      response to antibody-mediated receptor cross-linking was synergized in
      permeabilized T cells by either of two non-hydrolyzable GTP analogues, guanosine
      5'-[gamma-thio]triphosphate (GTP gamma S) or guanosine 5'-[beta, gamma
      imido]triphosphate Gpp(NH)p. ATP analogues did not significantly affect antibody
      induced tyrosine phosphorylation. Unlike the GTP analogues, the GDP analogue
      guanosine 5'-[beta-thio]diphosphate (GDP beta S) did not enhance phosphorylation
      of zeta. The effect induced by the GTP analogues required TCR occupancy and was
      independent of protein kinase C. Taken together these observations implicate a
      GTP-binding protein in the modulation of TCR-induced tyrosine phosphorylation.

PMID- 1386077
TI  - A cytosolic inhibitor of vacuolar H(+)-ATPases from mammalian kidney.
AB  - Regulation of the vacuolar H(+)-ATPase in organellar and transepithelial
      acidification has been attributed to the effects of the proton electrochemical
      gradient across the membrane or to changes in the number of proton pumps. We now
      report the identification and purification of a protein from bovine kidney
      cytosol that inhibits both ATPase activity and proton translocating activity of
      vacuolar H(+)-ATPases. Its relative molecular weight (M(r)) is 6300, similar to
      that for protein inhibitors of the mitochondrial F0F1-ATPase. The newly
      identified cytosolic inhibitor protein may participate in the physiologic
      regulation of the vacuolar H(+)-ATPase by suppressing activity directly.

PMID- 1386078
TI  - Regulation of vascular smooth muscle tone by caldesmon.
AB  - Caldesmon is an actin-binding protein present in smooth muscle cells that also
      inhibits actin-activated myosin ATPase activity. To assess the possible role of
      caldesmon in the regulation of smooth contraction, we investigated the effects of
      synthetic peptides on force directly recorded from single hyperpermeable smooth
      muscle cells of ferret aorta and portal vein. GS17C, a peptide that contains the
      residues from Gly651 to Ser667 of the caldesmon sequence plus an added cysteine
      at the C terminus, binds calmodulin in a Ca(2+)-dependent manner and also binds
      to F-actin but does not inhibit actomyosin ATPase activity (Zhan, Q., Wong, S.S.,
      and Wang, C.-L.A. (1991) J. Biol. Chem. 266, 21810-21814). In cells in which Ca2+
      was clamped at pCa 7.0, GS17C induced a dose-dependent contraction (EC50 = 0.92
      microM) in aorta cells, whereas it evoked little or no contraction in portal vein
      cells. The GS17C-induced contraction in aorta cells was inhibited at higher Ca2+
      concentrations (above pCa 6.6) and by pretreatment with calmodulin. Another
      peptide, C16AA, which contains the residues from Ala594 to Ala609 and does not
      bind actin or calmodulin, did not induce contraction. Our results strongly
      suggest that GS17C induces contraction by the displacement of the inhibitory
      region of endogenous caldesmon and, furthermore, that caldesmon present in these
      smooth muscle cells regulates contraction by providing a basal resting inhibition
      of vascular tone.

PMID- 1386079
TI  - A tissue-specific small nuclear ribonucleoprotein and the regulated splicing of
      the calcitonin/calcitonin gene-related protein transcript.
AB  - Based on a correlation between expression patterns of an abundant tissue-specific
      small nuclear ribonucleoprotein (N protein) and the calcitonin gene-related
      protein (CGRP) splicing choice, a small nuclear ribonucleoprotein (the N factor)
      has been hypothesized to potentially function as a trans-acting factor involved
      in the regulation of the alternative splicing of the calcitonin/CGRP transcript.
      RNA analysis indicated that most rat, human, and simian cell lines and tissues
      making the CGRP mRNA splicing choice expressed the N factor mRNA. These data led
      us to address the effect of ectopic expression of the N factor in HeLa cells,
      which exhibit a calcitonin splicing choice when expressing the calcitonin/CGRP
      gene. Expression of the N factor exerts no effect on the calcitonin/CGRP splicing
      choice in HeLa cells. Furthermore, several cell lines such as the human 293 cell
      line make the CGRP mRNA splicing choice in the absence of any detectable level of
      the mRNA encoding the N factor. Together, these data reveal that the N protein is
      neither sufficient nor required for the tissue-specific CGRP splicing decision
      and that the N protein is not the trans-acting factor regulating the alternative
      splicing of the calcitonin/CGRP gene.

PMID- 1386080
TI  - The mitochondrial F1ATPase alpha-subunit is necessary for efficient import of
      mitochondrial precursors.
AB  - The mitochondrial import and assembly of the F1ATPase subunits requires,
      respectively, the participation of the molecular chaperones hsp70SSA1 and
      hsp70SSC1 and other components operating on opposite sides of the mitochondrial
      membrane. In previous studies, both the homology and the assembly properties of
      the F1ATPase alpha-subunit (ATP1p) compared to the groEL homologue, hsp60, have
      led to the proposal that this subunit could exhibit chaperone-like activity. In
      this report the extent to which this subunit participates in protein transport
      has been determined by comparing import into mitochondria that lack the F1ATPase
      alpha-subunit (delta ATP1) versus mitochondria that lack the other major
      catalytic subunit, the F1ATPase beta-subunit (delta ATP2). Yeast mutants lacking
      the alpha-subunit but not the beta-subunit grow much more slowly than expected on
      fermentable carbon sources and exhibit delayed kinetics of protein import for
      several mitochondrial precursors such as the F1 beta subunit, hsp60MIF4 and
      subunits 4 and 5 of the cytochrome oxidase. In vitro and in vivo the F1 beta
      subunit precursor accumulates as a translocation intermediate in absence of the
      F1 alpha-subunit. In the absence of both the ATPase subunits yeast grows at the
      same rate as a strain lacking only the beta-subunit, and import of mitochondrial
      precursors is restored to that of wild type. These data indicate that the F1
      alpha-subunit likely functions as an "assembly partner" to influence protein
      import rather than functioning directly as a chaperone. These data are discussed
      in light of the relationship between the import and assembly of proteins in
      mitochondria.

PMID- 1386081
TI  - Energy-dependent efflux of methotrexate in L1210 leukemia cells. Evidence for the
      role of an ATPase obtained with inside-out plasma membrane vesicles.
AB  - Earlier studies from our laboratory (Dembo, M., Sirotnak F. M., and Moccio, D. M.
      (1984) J. Membr. Biol. 78, 9-17) suggested that methotrexate (MTX) efflux from
      L1210 cells was mediated predominantly by an ATP-dependent, outwardly directed,
      mechanism. To examine this process further, we utilized predominantly (74%)
      inside-out plasma membrane vesicle preparations derived from an L1210 cell
      variant (L1210/R24) with 15-fold reduced Vmax for [3H]MTX influx. Efflux of
      [3H]MTX, under nonionic buffer conditions, in these inside-out membrane vesicles
      was temperature and ATP dependent (apparent Km = 0.40 +/- 0.06 mM), osmotically
      sensitive, and unaffected by protonophores. The presence of K+, Na+, Cl-, and
      HCO3- at their physiological concentrations had no effect on [3H]MTX efflux.
      Other triphosphonucleotides (GTP and CTP), but not a nonhydrolyzable analogue,
      adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S), could also stimulate efflux,
      but to a lesser extent. Also, ATP gamma S and orthovanadate were potent
      inhibitors of ATP-dependent efflux of [3H]MTX. Other experiments revealed a
      system with low saturability for [3H]MTX during efflux (apparent Km = 46 +/- 7
      microM), but extremely high capacity (106 +/- 15 pmol/min/mg protein), and a pH
      optimum in the range of 5.5-6. However, appreciable efflux was measured in the
      physiological range of pH 6.7-6.9. A number of inhibitors or copermeants for ATP
      dependent [3H]MTX efflux in intact L1210 cells were inhibitors of ATP-dependent
      efflux in inside-out plasma membrane vesicles, including, cholate,
      bromosulfophthalein, verapamil, quinidine, and reserpine. These findings and
      other results showing that bromosulfophthalein will completely inhibit efflux are
      consistent with a role for an ATPase in [3H]MTX efflux, and suggest that the
      process under study is the bromosulfophthalein-sensitive, ATP-dependent route
      responsible for the majority of [3H]MTX efflux in intact L1210 cells.

PMID- 1386082
TI  - Movement of Cys-697 in myosin ATPase associated with ATP hydrolysis.
AB  - To detect movement of Cys-697 (SH2) in myosin subfragment-1 (S-1) associated with
      ATP hydrolysis, SH2 was labeled with the environmentally sensitive fluorescent
      analog of maleimide, 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid (MIANS).
      Complex formation of S-1 labeled at Cys-697 with MIANS (MIANS-S-1) with adenyl-5'
      yl imidodiphosphate and ADP resulted in a significant decrease in the
      fluorescence intensity of approximately 40 and 30%, respectively. When ATP was
      added to MIANS-S-1, the fluorescence intensity decreased rapidly by approximately
      40%, and this fluorescence level was maintained during the steady state of ATP
      hydrolysis. As the substrate was used up, the fluorescence intensity increased to
      approximately 70% of the original value. These results together with model
      experiments with MIANS-N-acetylcysteine indicate that in the presence of ATP, the
      MIANS fluorophore attached to SH2 is located in a less hydrophobic environment
      than is the fluorophore in the absence of ligand and that the hydrolysis of ATP
      enhances hydrophobicity around the fluorophore. Acrylamide fluorescence quenching
      studies of MIANS-S-1 confirmed these results, indicating that addition of ATP and
      ADP to MIANS-S-1 results in an increase in the Stern-Volmer quenching constant of
      the fluorophore by factors of approximately 3 and 2.5, respectively. The present
      observations suggest that binding of ATP causes a movement of SH2 toward the
      protein surface, whereas it goes back into the protein interior after ATP
      hydrolysis. The results also confirmed previous observations by a chemical cross
      linking approach (Hiratsuka, T. (1987) Biochemistry 26, 3168-3173).

PMID- 1386083
TI  - Spatial proximity of ATP-sensitive tryptophanyl residue(s) and Cys-697 in myosin
      ATPase.
AB  - The reactive thiol Cys-697 (SH2) in myosin ATPase was labeled with a fluorescent
      analog of maleimide, 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid (MIANS)
      (Hiratsuka, T. (1992) J. Biol. Chem. 267, 14941-14948). Although the tryptophan
      fluorescence of myosin subfragment-1 (S-1) was slightly affected by incorporation
      of the MIANS fluorophore, the tryptophan fluorescence of the resultant S-1
      derivative (MIANS-S-1) was enhanced by ATP in a manner similar to that of
      unlabeled S-1. The quenching of tryptophan fluorescence of MIANS-S-1 was shown to
      result from a transfer of the excitation energy from tryptophanyl residue(s) to
      the MIANS fluorophore attached to SH2, which absorbed and fluoresced maximally at
      325 and 418 nm, respectively. The energy transfer measurements were performed in
      the presence of acrylamide and compared to those performed in the absence of the
      quencher. The energy transfer efficiencies were found to be unaltered by
      acrylamide, indicating that the observed fluorescence energy transfer is
      originated exclusively from the tryptophanyl residue(s) that are not affected by
      acrylamide, i.e. the ATP-sensitive tryptophanyl residue(s) of S-1 (Torgerson, P.
      M. (1984) Biochemistry 23, 3002-3007). The distance between the tryptophanyl
      residue(s) and Cys-697 was calculated to be 27 A assuming a single donor-acceptor
      pair. Trp-510 is proposed to be one of the ATP-sensitive tryptophanyl residues.

PMID- 1386084
TI  - Deep penetration of a portion of Escherichia coli SecA protein into model
      membranes is promoted by anionic phospholipids and by partial unfolding.
AB  - SecA protein, a principal component of the protein export machinery of
      Escherichia coli, is found both in the cytoplasm and inner membrane of cells.
      Previous in vitro and in vivo studies demonstrated that the interaction of SecA
      with the inner membrane requires the presence of physiological levels of anionic
      (acidic) phospholipids. In this report the degree of SecA insertion into model
      membranes and the conformational changes associated with this event have been
      examined. The extent of association of SecA with model membranes was determined
      by photolabeling with a hydrophobic reagent, and the depth of insertion of the
      protein into the phospholipid bilayer was determined by the amount of quenching
      of SecA fluorescence by both brominated and spin-labeled phospholipids. These
      methods demonstrated that SecA penetrates deep within the acyl chain region of
      the phospholipid bilayer. It was also found that SecA penetration into vesicles
      was associated with a major conformational change in the protein. This change can
      be induced by higher temperatures and involves a partial unfolding event as
      judged by differential scanning calorimetry, SecA fluorescence and increased
      sensitivity to proteolysis. These properties suggest the induction of a molten
      globule-like conformation in a portion of the SecA polypeptide. This change was
      also induced at lower temperatures by the presence of membranes containing a
      physiological amount of the anionic phospholipid, phosphatidylglycerol. The
      partial unfolding and concomitant deep insertion of SecA into membranes may aid
      in the insertion of precursor proteins into the inner membrane and may influence
      possible interactions between SecA and the integral membrane export machinery
      components.

PMID- 1386085
TI  - Glomerular actions of a free radical-generated novel prostaglandin, 8-epi
      prostaglandin F2 alpha, in the rat. Evidence for interaction with thromboxane A2
      receptors.
AB  - 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) and related compounds are novel
      prostanoid produced by a noncyclooxygenase mechanism involving lipid
      peroxidation. Renal ischemia-reperfusion injury increased urinary excretion of
      these compounds by 300% over baseline level. Intrarenal arterial infusion at 0.5,
      1, and 2 micrograms/kg per min induced dose-dependent reductions in glomerular
      filtration rate (GFR) and renal plasma flow, with renal function ceasing at the
      highest dose. Micropuncture measurements (0.5 microgram/kg per min) revealed a
      predominant increase in afferent resistance, resulting in a decrease in
      transcapillary hydraulic pressure difference, and leading to reductions in single
      nephron GFR and plasma flow. These changes were completely abolished or reversed
      by a TxA2 receptor antagonist, SQ 29,548. Competitive radioligand binding studies
      demonstrated that 8-epi-PGF2 alpha is a potent competitor for [3H]SQ 29,548
      binding to rat renal arterial smooth muscle cells (RASM) in culture. Furthermore,
      addition of 8-epi-PGF2 alpha to RASM or isolated glomeruli was not associated
      with stimulation of arachidonate cyclooxygenase products. Therefore, 8-epi-PGF2
      alpha is a potent preglomerular vasoconstrictor acting principally through TxA2
      receptor activation. These findings may explain, in part, the beneficial effects
      of antioxidant therapy and TxA2 antagonism observed in numerous models of renal
      injury induced by lipid peroxidation.

PMID- 1386086
TI  - Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in
      vivo as well as in vitro in Salmonella infection.
AB  - Gamma delta T cell receptor-positive cells (gamma delta T cells) have recently
      been implicated to play a role in the protection against infectious pathogens.
      Serial studies on gamma delta T cells in 14 patients with salmonella infection
      have revealed that the proportions of gamma delta T cells (mean +/- SD: 17.9 +/-
      13.2%) in salmonella infection were significantly increased (P less than 0.01)
      compared with 35 normal controls (5.0 +/- 2.6%) and 13 patients with other
      bacterial infections (4.0 +/- 1.4%). Expansion of gamma delta T cells was more
      prominent in the systemic form (28.9 +/- 10.8%) than in the gastroenteritis form
      (10.5 +/- 7.9%) of salmonella infection (P less than 0.01). Most in vivo-expanded
      gamma delta T cells expressed V gamma 9 gene product. Increased activated (HLA
      DR+) T cells were observed in all the six patients with the systemic form and
      four of the seven with gastroenteritis form. Especially in the six with systemic
      form, gamma delta T cell activation was significantly higher than alpha beta T
      cell activation at the early stage of illness (P less than 0.01). When peripheral
      blood lymphocytes from normal individuals were cultured with live salmonella,
      gamma delta T cells were preferentially activated and expanded and most of them
      expressed V gamma 9. Purified gamma delta T cells also responded to live
      salmonella in vitro. The present study suggests that human gamma delta T cells
      play a role in the protection against salmonella infection in vivo.

PMID- 1386087
TI  - Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma
      lipoprotein(a) concentrations.
AB  - Plasma lipoprotein(a) [Lp(a)], a low density lipoprotein particle with an
      attached apolipoprotein(a) [apo(a)], varies widely in concentration between
      individuals. These concentration differences are heritable and inversely related
      to the number of kringle 4 repeats in the apo(a) gene. To define the genetic
      determinants of plasma Lp(a) levels, plasma Lp(a) concentrations and apo(a)
      genotypes were examined in 48 nuclear Caucasian families. Apo(a) genotypes were
      determined using a newly developed pulsed-field gel electrophoresis method which
      distinguished 19 different genotypes at the apo(a) locus. The apo(a) gene itself
      was found to account for virtually all the genetic variability in plasma Lp(a)
      levels. This conclusion was reached by analyzing plasma Lp(a) levels in siblings
      who shared zero, one, or two apo(a) genes that were identical by descent (ibd).
      Siblings with both apo(a) alleles ibd (n = 72) have strikingly similar plasma
      Lp(a) levels (r = 0.95), whereas those who shared no apo(a) alleles (n = 52), had
      dissimilar concentrations (r = -0.23). The apo(a) gene was estimated to be
      responsible for 91% of the variance of plasma Lp(a) concentration. The number of
      kringle 4 repeats in the apo(a) gene accounted for 69% of the variation, and yet
      to be defined cis-acting sequences at the apo(a) locus accounted for the
      remaining 22% of the inter-individual variation in plasma Lp(a) levels. During
      the course of these studies we observed the de novo generation of a new apo(a)
      allele, an event that occurred once in 376 meioses.

PMID- 1386088
TI  - Alterations of phasic coronary artery flow velocity in humans during percutaneous
      coronary angioplasty.
AB  - BACKGROUND AND OBJECTIVES: Studies using Doppler catheters to assess blood flow
      velocity and vasodilator reserve in proximal coronary arteries have failed to
      demonstrate significant improvement immediately after coronary angioplasty.
      Measurement of blood flow velocity, flow reserve and phasic diastolic/systolic
      velocity ratio performed distal to a coronary stenosis may provide important
      information concerning the physiologic significance of coronary artery stenosis.
      This study was designed to measure these blood flow velocity variables both
      proximal and distal to a significant coronary artery stenosis in patients
      undergoing coronary angioplasty. METHODS: A low profile (0.018-in.) (0.046-cm)
      Doppler angioplasty guide wire capable of providing spectral flow velocity data
      was used to measure blood flow velocity, flow reserve and diastolic/systolic
      velocity ratio both proximal and distal to left anterior descending or left
      circumflex coronary artery stenosis. These measurements were made in 38 patients
      undergoing coronary angioplasty and in 12 patients without significant coronary
      artery disease. RESULTS: Significant improvement in mean time average peak
      velocity was noted in distal coronary arteries after angioplasty (before 19 +/-
      12 cm/s; after 35 +/- 16 cm/s; p less than 0.01). Increases in proximal average
      peak velocity after angioplasty were less remarkable (before 34 +/- 18 cm/s;
      after 41 +/- 14 cm/s; p = 0.04). Mean flow reserve remained unchanged after
      angioplasty both proximal (1.5 +/- 0.5 vs. 1.6 +/- 1; p greater than 0.10) and
      distal (1.6 +/- 1 vs. 1.5 +/- 0.8; p greater than 0.10) to a coronary stenosis.
      Before angioplasty, mean diastolic/systolic velocity ratio measured distal to a
      significant stenosis was decreased compared with that in normal vessels (1.3 +/-
      0.5 vs. 1.8 +/- 0.5; p less than 0.01). After angioplasty, distal abnormal phasic
      velocity patterns generally returned to normal, with a significant increase in
      mean diastolic/systolic velocity ratio (1.3 +/- 0.5 vs. 1.9 +/- 0.6; p less than
      0.01). Phasic velocity patterns and mean diastolic/systolic velocity ratio
      measured proximal to a coronary stenosis were not statistically different from
      values in normal vessels (1.8 +/- 0.8 vs. 1.8 +/- 0.5; p greater than 0.10) and
      did not change significantly after angioplasty (1.8 +/- 0.8 vs. 2.13 +/- 0.9; p
      greater than 0.10). CONCLUSIONS: Flow velocity measurements may be performed
      distal to a coronary stenosis with the Doppler guide wire. Phasic velocity
      measurements made proximal to a coronary stenosis differed from those in the
      distal coronary artery. Both proximal and distal flow reserve measurements made
      immediately after angioplasty were of limited utility. Changes in distal flow
      velocity patterns and diastolic/systolic velocity ratio appeared to be more
      relevant than the hyperemic response in assessing the immediate physiologic
      outcome of coronary angioplasty.

PMID- 1386089
TI  - Intramural methotrexate therapy for the prevention of neointimal thickening after
      balloon angioplasty.
AB  - OBJECTIVES: The study was performed to test the hypothesis that high local,
      intramural concentrations of antineoplastic agents at the site of balloon injury
      inhibit vascular smooth muscle cell proliferation without systemic toxicity.
      BACKGROUND: The predominant mechanism for recurrent stenosis after coronary
      balloon angioplasty is neointimal thickening due to medial smooth muscle cell
      proliferation. The clinical use of potent antiproliferative agents to prevent
      restenosis has been limited by the potential for severe systemic side effects.
      Local therapy with these agents may be effective and free of systemic
      complications. METHODS: After bilateral balloon angioplasty of the carotid
      arteries of 14 juvenile farm pigs, the dilated arterial segments were treated
      locally with methotrexate (6.25 mg/ml, total dose 25 mg) or 0.9% saline solution
      through a perforated balloon catheter. The animals were then killed 30 days after
      balloon injury to determine the effects of this therapy on neointimal thickness.
      In an additional six animals, tritium-labeled methotrexate was used to determine
      the concentration and duration of detectability of methotrexate in the wall of
      the treated arteries and in the systemic circulation. RESULTS: Two hours after
      drug instillation the concentration of labeled drug was greater than 1,000-fold
      greater in the wall of the treated artery than in circulating blood, and this
      ratio remained between 50 and 100 for at least 7 days. Despite this difference,
      the mean intimal thickness 30 days after the procedure was similar in the 10
      methotrexate-treated arteries and the 18 saline-treated arteries (59 +/- 30 vs.
      56 +/- 25 microns, p = 0.6). The morphologic appearance of the neointima was
      similar in each group and suggested an important role for mural thrombus in the
      genesis of the intimal thickening. CONCLUSIONS: Treatment with intramural
      methotrexate, delivered through a perforated balloon catheter at the selected
      concentration and total dose, failed to prevent intimal thickening after balloon
      injury. Nonetheless, the perforated balloon catheter appears to be a promising
      means of delivering a high local concentration of drugs with potentially life
      threatening systemic side effects. The optimal concentrations and combinations of
      candidate drug therapies warrant further evaluation.

PMID- 1386090
TI  - The dynamics of disability and functional change in an elderly cohort: results
      from the Alameda County Study.
AB  - OBJECTIVE: To examine changes in functional status over time by age, gender, and
      ethnicity in a representative sample of older persons. DESIGN: Six-year
      prospective cohort study. SETTING: Alameda County, California. PARTICIPANTS: 508
      persons 65 years old and older at baseline in 1984. MAIN OUTCOME MEASURES:
      Activities of daily living (ADL) dependence, mobility impairment, and functioning
      on an 18-item scale. RESULTS: The prevalence of ADL dependence and mobility
      impairment at baseline increased with age, while function decreased. Particularly
      striking differences occurred for those 80 and older. Changes in function over
      the 6-year follow-up showed a similar pattern. While death rates for males were
      higher, females had poorer initial functioning, and surviving females declined
      more than surviving males. The incidence of ADL dependence and mobility
      impairment during follow-up was similar for males and females, although females
      survived longer with incident disability than did males. Blacks had poorer
      baseline functioning, more ADL dependence and mobility impairment, and declined
      more than non-Blacks during follow-up. Some of the baseline difference in
      function between Blacks and non-Blacks was due to higher rates of chronic illness
      and co-morbidity. In spite of the general downward trend in functioning over the
      6 years, 13% of the males and 20% of the females improved. CONCLUSION: Age
      related changes in function for older persons are complex and result in much
      heterogeneity. Clarifying the reasons for such heterogeneity is an important and
      challenging area of research.

PMID- 1386091
TI  - The physician and Down syndrome: are attitudes changing?
AB  - A survey of attitudes of pediatricians, child neurologists, and pediatric
      surgeons toward Down syndrome is compared with a similar study reported in 1975.
      A contemporary physician would be much more aggressive in treating a child with
      Down syndrome who has associated anomalies such as duodenal atresia or congenital
      heart disease. Few would recommend institutionalization of a person with Down
      syndrome; the majority expect that such individuals could productively spend
      their adult lives in group homes. Positive changes in physicians' attitudes
      during the past 15 years have been influenced by parent advocacy groups, court
      decisions, and studies showing that the ultimate intellectual and social skills
      of Down syndrome children are greater than was previously believed. The most
      prominent variable associated with attitudes was the physician's age: the older
      the physician, the more likely he or she would be nonsupportive of active
      treatment on behalf of the Down syndrome individual. These findings suggest that
      ongoing education of medical students and pediatric residents in the field of
      developmental disabilities and bioethics is required in order to promote well
      informed advocacy for the mentally handicapped.

PMID- 1386092
TI  - IL-1 receptor antagonist protein production and gene expression in rheumatoid
      arthritis and osteoarthritis synovium.
AB  - IL-1 can participate in the perpetuation of arthritis through direct stimulation
      of synoviocytes and augmentation of matrix degradation. Hence, local production
      of the IL-1R antagonist protein (IRAP) might be an important negative feedback
      signal that regulates synovitis. We assessed synovial IRAP production in synovia
      from 30 individuals, by using a specific mAb and the immunoperoxidase staining
      method. IRAP was detected in 11 of 12 rheumatoid arthritis (RA) synovial tissues
      (ST) and was located primarily in the sublining, particularly in perivascular
      regions enriched for macrophages. Some staining was observed in the intimal
      lining of the synovium, although this was significantly less than in the
      sublining (p less than 0.05). Nine of 12 osteoarthritis (OA) tissues were
      positive for IRAP. In contrast to RA, the staining was observed primarily in the
      synovial lining in OA, with only minimal sublining IRAP being detected. Synovia
      from four patients without arthritis were negative (three autopsy specimens and
      one post-traumatic sample). Of the other two patients with miscellaneous
      diagnoses, one sample was negative (tenosynovitis) and one was positive
      (seronegative inflammatory arthritis) (sublining). Studies of serial sections and
      double-immunostaining experiments indicated that macrophages are the major cells
      containing immunoreactive IRAP. IRAP gene expression in vivo was determined by
      performing in situ hybridization on ST from 17 arthritis patients. RNA sense IRAP
      probes did not hybridize to any tissues. Anti-sense IRAP probes bound to two of
      nine RA tissues, two of six OA tissues, one of one seronegative inflammatory
      arthropathy tissue, and none of one flexor tenosynovitis tissue. As with
      immunoreactive protein, IRAP mRNA was primarily localized to cells in the
      synovial lining in OA but was more prominent in perivascular lymphoid aggregates
      in RA and seronegative inflammatory arthropathy. Northern blot analysis was
      performed on RNA isolated from nine ST. The appropriately sized IRAP band was
      identified in six of nine samples (five of six RA and one of three OA).
      Supernatants from cultured RA and OA ST cells contained immunoreactive and
      biologically active IRAP. Hence, IRAP gene expression and protein production
      occur in RA and OA synovium, albeit in different distributions.

PMID- 1386093
TI  - Expression, molecular association, and functions of C3 complement receptors CR1
      (CD35) and CR2 (CD21) on the human T cell line HPB-ALL.
AB  - We have investigated the expression, molecular association, ligand binding
      properties, and ability to transduce intracellular signals of CR1 and CR2 C3
      receptors on cells of the human HPB-ALL T cell line. CR1 and CR2 on HPB-ALL cells
      bound polymeric C3b and C3dg and several anti-CR1 and anti-CR2 mAb recognizing
      different epitopes of the receptors on normal peripheral blood cells.
      Immunoprecipitated CR1 and CR2 exhibited similar m.w. to those of the receptors
      on normal peripheral blood T and B lymphocytes. CR1 and CR2 were partially
      associated in the form of CR1/CR2 complexes in the cell membrane as assessed by
      the ability of the receptors to cocap and cointernalize and to form a detergent
      sensitive complex upon immunoprecipitation analysis. Triggering of CR2 with mAb
      OKB7 that recognizes an epitope associated with the ligand binding site of the
      receptor induced an increase in intracellular free calcium concentration in HPB
      ALL cells. The signal provided by mAb OKB7 did not synergize with that triggered
      by anti-CD3 mAb UCHT1. Triggering of CR1 did not result in changes in
      intracellular free calcium concentration. Our observations have significance for
      the biology of normal human T cells because the majority of peripheral blood T
      cells that express CR1 also expressed CR2 and because a change in (Ca2+)i was
      induced by mAb OKB7 in purified normal T cells. These functions may be relevant
      for the regulatory role of C3 fragments on the immune response to T-dependent Ag
      and for the penetration into T cells of lymphocytotropic viruses.

PMID- 1386094
TI  - Different subsets of T cells in the adult mouse bone marrow and spleen induce or
      suppress acute graft-versus-host disease.
AB  - Fractionation of normal adult mouse spleen and bone marrow cells (C57BL/Ka) was
      performed by discontinuous Percoll density gradients. The fractionated low
      density (1.050-1.060 g/ml) C57BL/Ka spleen cells completely suppressed acute
      lethal graft vs host disease (GVHD) when coinjected with unfractionated C57BL/Ka
      spleen cells into sublethally irradiated (400 rad) BALB/c mice. In dose response
      experiments, as few as 0.5 x 10(6) low density cells from the spleen fractions
      suppressed acute GVHD induced by 2.5 x 10(6) unfractionated allogeneic spleen
      cells. Although the low density spleen fractions inhibited acute GVHD, the high
      density (1.075-1.090 g/ml) spleen fractions induced acute GVHD in sublethally
      irradiated BALB/c recipients. Fractionation of C57BL/Ka bone marrow cells showed
      that none of the high or low density fractions or unfractionated cells induced
      lethal GVHD. When these fractions were tested for their capacity to suppress GVHD
      by coinjection with C57BL/Ka unfractionated spleen cells, all fractions protected
      the BALB/c recipients. Unfractionated bone marrow cells showed modest protection.
      Evaluation of the dose response characteristics of the suppressive activity of
      the low and middle density (1.060-1.068 g/ml) bone marrow cell fraction showed
      that reproducible protection could be achieved at a 5:1 ratio of inducing to
      suppressing cells. The low density fractions of both bone marrow and spleen cells
      had a marked depletion of typical TCR(+)-alpha beta CD4+ or CD8+ T cells, and a
      predominant population of TCR(+)-alpha beta CD4- CD8- T cells. Purified
      populations of the latter cells suppressed GVHD. Recipients given unfractionated
      C57BL/Ka spleen cells and protected with low-density bone marrow or spleen cells
      were chimeras.

PMID- 1386095
TI  - Structure of the gene for the alpha-chain of the mouse high affinity receptor for
      IgE (Fc epsilon RI).
AB  - Full-length genomic clones for the alpha-chain of mouse Fc epsilon RI were
      isolated and the exon/intron structure of the gene determined. The gene consisted
      of 5 exons, of which the first and second comprised the 5' untranslated region
      and the leader sequence; the third and fourth, the extracellular domain; and the
      fifth, the transmembrane and cytosolic domains, plus the 3' untranslated region.
      The upstream region was highly homologous to that of the rat counterpart. Primer
      extension and RNase protection analyses revealed multiple transcription
      initiation sites, between 30 and 120 nucleotides 3' of the putative TATA box.
      Comparison with other Fc receptor genes (rat Fc epsilon RI, mouse Fc gamma RIII
      alpha, human Fc gamma RIIIB and human Fc gamma RIIIA alpha) revealed a high
      degree of gene organization conservation.

PMID- 1386096
TI  - IL-4 up-regulates IL-1 receptor antagonist gene expression and its production in
      human blood monocytes.
AB  - IL-4 down-regulates the productions of IL-1 and TNF-alpha in human monocytes. We
      examined whether the productions of IL-1 and a specific receptor antagonist of IL
      1 (IL-1Ra) in human blood monocytes were regulated differently. Highly purified
      blood monocytes, isolated by centrifugal elutriation from healthy donors, were
      stimulated with LPS in the presence or absence of IL-4, and their productions of
      IL-1 and IL-1Ra were measured by Northern blot and immunoblot analyses. IL-1 and
      IL-1Ra were produced by monocytes stimulated with LPS, but not with IL-4 alone.
      Marked up-regulation by IL-4 of IL-1Ra production in LPS-stimulated monocytes was
      observed at both the mRNA and protein levels. Maximal expressions of IL-1 beta
      and IL-1Ra mRNA in LPS-stimulated monocytes were observed 2 h and 8 h,
      respectively, after stimulation. The enhancement of IL-1Ra production by IL-4 was
      concluded to be due to enhanced gene transcription, because there was no
      difference in the half-lives of IL-1Ra mRNA in monocytes cultured with and
      without IL-4. Up-regulation of IL-1Ra production by IL-4 was also observed in
      monocytes stimulated with adherent IgG at both the mRNA and protein levels. This
      unique property of IL-4 may be important in down-regulation of the IL-1-initiated
      immune and/or inflammatory response, not only directly through inhibition of IL-1
      production, but also indirectly through up-regulation of IL-1Ra production.

PMID- 1386097
TI  - Efficacy of hepatitis B vaccination in primary school children from a village
      endemic for Schistosoma mansoni.
AB  - To determine whether chronic Schistosoma mansoni infection interferes with
      hepatitis B virus (HBV) immunization, 308 schoolchildren aged 6-12 years with no
      evidence of prior HBV infection (156 with active schistosomiasis) were vaccinated
      with three 5-micrograms injections of recombinant DNA-derived HBV vaccine. The
      vaccine was given in the deltoid muscle at time 0 and 1 and 7 months later. All
      vaccinees were examined 1 and 3 years after vaccination for quantitative antibody
      to hepatitis B surface antigen (anti-HBs). Seroconversion was detected in 284
      vaccinated children (92%), of whom 271 had a good (51-300 mIU/mL) or excellent
      (greater than 300 mIU/mL) anti-HBs response. Sixteen other children (5%) had
      evidence of natural HBV infection (antibody to hepatitis B core antigen). Of
      those with good or excellent response, 99% retained high antibody titers for 3
      years. Response was not influenced by S. mansoni infection. Hepatomegaly and
      splenomegaly were associated with reduced vaccine response.

PMID- 1386098
TI  - Skin, soft tissue, and bone infections due to Mycobacterium chelonae chelonae:
      importance of prior corticosteroid therapy, frequency of disseminated infections,
      and resistance to oral antimicrobials other than clarithromycin.
AB  - Little is known of clinical disease due to Mycobacterium chelonae chelonae. One
      hundred skin, soft tissue, or bone isolates of this rapidly growing mycobacterium
      were identified over 10 years. Clinical disease included disseminated cutaneous
      infection (53%); localized cellulitis, abscess, or osteomyelitis (35%); and
      catheter infections (12%). Underlying conditions with disseminated infection
      included organ transplantation, rheumatoid arthritis, and autoimmune disorders;
      92% involved corticosteroid use. Trauma and medical procedures were risk factors
      for localized infections. Corticosteroids and chronic renal failure were risk
      factors for catheter infections. Overall, 62% of patients were receiving
      corticosteroids and 72% were immunosuppressed. MICs of six oral antimicrobials
      were obtained for 180 isolates by broth microdilution. Up to 20% of isolates were
      susceptible to doxycycline, ciprofloxacin, ofloxacin, and sulfamethoxazole. In
      contrast, 100% were susceptible to clarithromycin (MICs less than or equal to 1
      microgram/mL). Disease due to M. chelonae chelonae usually occurs in the setting
      of corticosteroid therapy and is often disseminated; the organisms require high
      MICs of oral antimicrobials other than clarithromycin.

PMID- 1386099
TI  - Streptokinase-producing streptococci grown in human plasma acquire unregulated
      cell-associated plasmin activity.
AB  - Group A streptococci grown in the presence of human plasma generated plasmin from
      plasminogen and captured the functional enzyme to a specific cell-surface
      receptor. Bacteria-bound plasmin was not regulated by alpha 2-antiplasmin present
      in the medium. The ability of the bacteria to acquire cell-associated plasmin
      activity was dependent on both the presence of plasminogen in the culture medium
      and the production of a bacterial plasminogen activator, streptokinase. The
      ability of group A streptococci to produce a plasminogen activator and capture
      resulting plasmin in an unregulatable form could provide the organism with a
      mechanism for invasion of normal tissue barriers.

PMID- 1386100
TI  - Lumbar motion trends and correlation with low back pain. Part II. A
      roentgenological evaluation of quantitative segmental motion in lateral bending.
AB  - OBJECTIVE: A radiographic study was undertaken to describe the relationship
      between the magnitude of coupled lumbar motion in lateral bending and the
      presence of low back pain: correlation between pain and motion, relationship
      between motion category and motion and symmetry of lumbar motion. DESIGN: Survey.
      SETTING: Chiropractic college student health center and private chiropractic
      clinic. PARTICIPANTS: 249 subjects: 114 with low back pain, 29 asymptomatic with
      no history and 106 asymptomatic with history. Of these, 194 were freshman
      volunteers and 55 were new private clinic low back pain patients. INTERVENTIONS:
      None. MAIN OUTCOME MEASURES: Net lumbar segmental tilt and rotation in lateral
      bending: corrected and uncorrected for segmental malposition with the patient
      standing in the upright neutral position. RESULTS: Statistical analysis
      demonstrated no significant relationship between coupled lumbar motion and low
      back pain (p greater than .01). The presence of type II motion could account for,
      on average, less than 5% loss of segmental tilt in the lumbar spine. Asymmetries
      between left and right side motion averaged 45 to 100% of unilateral range of
      motion. CONCLUSIONS: This study suggests that back pain is not an indication for
      the routine use of lateral bending films for the identification of alterations in
      the magnitude of lumbar segmental motion in lateral bending. It further indicates
      that type II motion cannot be ruled out as a normal variant. The paucity of
      symmetrical lumbar motion suggests that segmental tilt or coupled rotation
      asymmetry, in and of itself, should not be considered an indication for spinal
      manipulation.

PMID- 1386101
TI  - Lumbar apophyseal ring fractures in adolescents.
AB  - Fracture of the vertebral ring apophysis in the lumbar spine is an uncommon
      condition that has been reported in adolescent patients presenting with low back
      pain. The pathophysiology is considered to be a fracture of the posterior ring
      apophysis in association with a herniated disc. The nature and the extension of
      the lesion is best established by computed tomography scan with sagittal
      reconstruction. We present three cases to illustrate the classic clinical and
      radiologic findings. Management of the condition is also discussed.

PMID- 1386102
TI  - The beneficial effects of a thromboxane receptor antagonist on spinal cord
      perfusion following experimental cord injury.
AB  - The eicosanoids thromboxane A2 and prostacyclin have opposing actions causing
      vasoconstriction and vasodilation respectively. The ratio of these two
      eicosanoids is thus an important determinant of circulatory homeostasis. An
      increase in this ratio occurs in certain inflammatory conditions with dramatic
      consequences in organ perfusion. In spinal cord trauma, in addition to direct
      physical perturbation of the spinal cord, it is likely that further structural
      and functional loss occurs as a result of decreased tissue perfusion precipitated
      by an increase in the thromboxane/prostacyclin ratio. This study evaluated
      hemodynamics and organ perfusion, 3 h following 24 g-cm spinal cord trauma in the
      rat. The role of thromboxane was investigated with an inhibitor of thromboxane
      synthesis (Dazoxiben) and with a receptor antagonist (13-APT). Cardiac output and
      blood pressure were unaffected by Dazoxiben, 13-APT, or spinal cord trauma.
      Injury effected approximately a 40% decrease in spinal cord perfusion from 0.41
      to 0.25 ml/min/g which was not improved by the thromboxane synthase inhibitor,
      Dazoxiben. 13-ATP completely abrogated the decline in spinal cord blood flow
      flowing injury. Perfusion of other selected organs demonstrated little change as
      a result of the spinal trauma. Brain flow remained constant at 0.78 ml/min/g
      brain. Coronary blood flow, however, declined from 3.2 to 2.0 ml/min/g heart
      tissue. The data suggest consideration of the importance of thromboxane in
      therapeutic attempts to reduce secondary injury arising in spinal cord trauma.

PMID- 1386103
TI  - Meta-analysis of chemotherapy in multiple myeloma.

PMID- 1386104
TI  - In-vivo SPECT imaging of D2 receptor with iodine-iodolisuride: results in
      supranuclear palsy.
AB  - We assessed the potential use of [123I]iodolisuride (ILIS), a new iodine ergolene
      derivative, to study human striatal D2 dopamine receptors with SPECT. In normal
      subjects, we found that the tracer accumulated preferentially in striatum. This
      was prevented by high doses of haloperidol. The striatal accumulation was maximal
      between 60 and 180 min after injection. The striatum-to-cerebellum radioactivity
      concentration ratio as an index of specific binding, measured 60 min after
      injection, was 1.52 +/- 0.19 (mean +/- s.d.) in controls and 1.36 +/- 0.11 in
      patients with supranuclear palsy (p less than 0.03). Our results show that ILIS
      may be used to study D2 receptors with SPECT. In-vivo changes of D2 receptors in
      human brain may be detected with this method.

PMID- 1386105
TI  - Angiotensin converting enzyme inhibitors and the cardiovascular system.
AB  - OBJECTIVE: To show that angiotensin converting enzyme (ACE) inhibitors benefit
      the cardiovascular system to a greater extent than other antihypertensive agents.
      DATA EXTRACTION: An extensive literature search has shown that ACE inhibitors can
      induce regression of left ventricular hypertrophy, which may improve systolic
      and/or diastolic function in the left ventricle; increase in arterial compliance;
      and improve clinical signs of congestive heart failure and reduce mortality in
      patients with severe heart failure. In addition, ACE inhibitors have either a
      neutral or a beneficial effect on blood lipids and lipoproteins. These agents
      also have potential anti-ischaemic and anti-arrhythmic activity but do not
      depress resting cardiac function. CONCLUSION: ACE inhibitors are uniquely
      valuable first-line antihypertensive agents, especially in patients with
      cardiovascular risk.

PMID- 1386106
TI  - Immunohistochemical studies on the innervation of human transplanted liver.
AB  - The changing pattern of innervation in the human transplanted liver was studied
      from the day of transplantation to 5 years later. Seven liver biopsies from non
      transplant controls, 37 liver biopsies from 22 transplant patients, and one of
      these biopsied livers removed at retransplantation, were available for the study.
      Sections were immunostained for protein gene product 9.5 (PGP 9.5), neurone
      specific enolase (NSE), S-100 protein, and vasoactive intestinal polypeptide. NSE
      and PGP 9.5 demonstrated nerves most successfully in our tissues. Staining for
      most small nerves was reduced by day 5 post-transplantation. Scanty fine nerves
      could be detected from day 13 to day 241 in occasional biopsies. Consistently
      identifiable immunostaining of PGP 9.5 and NSE nerve fibres was again apparent in
      portal areas after this time in all but one case. The findings indicate that in
      transplanted liver limited reinnervation can eventually take place. This could be
      due to either proliferation of intrinsic nerves, or regrowth of extrinsic nerves,
      or both.

PMID- 1386107
TI  - Hepatic reinnervation following orthotopic liver transplantation in man.
AB  - We have studied changes in the pattern of intrinsic hepatic innervation in
      sequential liver biopsies from 16 patients who underwent orthotopic liver
      transplantation. Seventy-one needle biopsies were used, including specimens
      obtained at the time of transplantation (time zero) and up to 4 years post
      transplantation; five transplant hepatectomy tissue blocks removed 3-32 months
      after transplantation were also assessed. Paraffin sections were immunostained
      with anti-PGP 9.5 and anti-S-100 to identify nerve fibres. All 'time zero'
      biopsies contained portal nerves and all but two showed staining of parenchymal
      fibres. After 1 week, no subsequent biopsies contained parenchymal fibres. The
      disappearance of portal fibres was less rapid and showed greater variability
      between patients, but they had all disappeared by 6 weeks and there was no
      positive staining between 6 and 60 weeks. Thereafter, a minority of biopsies
      showed innervation of a few small portal tracts. Samples from the porta hepatis,
      hepatectomy specimens, and needle biopsies containing large tracts showed
      persistence of major nerve trunks at all stages. Abnormally large nerve bundles
      were seen in some of these areas. The pattern of nerve staining showed no obvious
      relationship to the intensity of rejection changes. Our results suggest that
      there is a limited, delayed capacity for regeneration of portal, but not
      parenchymal, fibres in the transplanted human liver. The physiological
      significance of this long-term parenchymal denervation in transplanted livers
      remains to be determined.

PMID- 1386108
TI  - Comparative investigation of the photosensitizing activity of hematoporphyrin
      derivative.

PMID- 1386109
TI  - Isoenzyme analysis of Hammondia hammondi and Toxoplasma gondii sporozoites.
AB  - Isoenzyme analysis using isoelectrofocusing in polyacrylamide gels was used to
      distinguish Hammondia hammondi and Toxoplasma gondii sporozoites. Five enzyme
      systems were studied: aconitase (EC 4.2.1.3), aspartate aminotransferase (EC
      2.6.1.1), glucose phosphate isomerase (EC 5.3.1.9), lactate dehydrogenase (EC
      1.1.1.27), and phosphoglucomutase (EC 2.7.5.1). Three stocks of T. gondii
      belonging to 3 zymodemes were compared to 1 stock of H. hammondi. Hammondia
      hammondi differed from T. gondii at all 5 loci analyzed. This was observed for
      all 3 zymodemes of T. gondii. These results indicated clear genetic differences
      between the 2 species.

PMID- 1386110
TI  - Comparison of isozyme patterns between Spirometra erinacei and Spirometra
      mansonoides by isoelectric focusing.
AB  - No differences were observed in the isozyme patterns of 4 enzymes examined
      between fresh samples stored at -80 C and samples stored at room temperature for
      10 days after lyophilization, which supports the validity of comparing
      lyophilized samples to fresh frozen tissue. Mature proglottids as well as
      plerocercoids of Spirometra erinacei from Japan and Australia were
      indistinguishable by comparison of isozyme patterns after isoelectric focusing.
      The isozyme patterns of acid phosphatase, glucosephosphate isomerase (GPI), and
      mannosephosphate isomerase from plerocercoids of Spirometra mansonoides were
      distinctly different from those of plerocercoids of S. erinacei. The adenylate
      kinase isozyme patterns of the mature proglottids of S. mansonoides were also
      distinctly different from those of the mature proglottids and the plerocercoids
      of S. erinacei. The GPI isozyme pattern of the mature proglottids of S.
      mansonoides was also distinguishable from the GPI patterns of those of S.
      erinacei. These electrophoretic data suggest that the S. erinacei from Japan and
      Australia are closely related, if not identical, but that S. mansonoides is
      genetically distinct from S. erinacei.

PMID- 1386111
TI  - CD8+ T lymphocytes are not required for murine resistance to human filarial
      parasites.
AB  - Mice are resistant to the establishment of infection with the nematode parasite
      Brugia malayi, an etiologic agent of human lymphatic filariasis. We have recently
      shown that T and B lymphocyte-deficient C.B.-17 scid/scid mice are permissive for
      infection with this parasite, whereas coisogenic C.B.-17+/+ mice are resistant.
      This observation suggests that T and B lymphocytes that comprise the antigen
      specific immune system orchestrate murine resistance to B. malayi. In order to
      define the component of the antigen-specific immune response that is responsible
      for this resistance, we have tested the susceptibility of beta 2M-/- mice to
      infection with B. malayi L3 larvae. These mice are homozygous for insertional
      disruption of their B2m genes, which encode beta 2-microglobulin, the small
      subunit of the major histocompatibility (MHC) antigens. They do not express beta
      2-microglobulin and, as a consequence, fail to express the class I major
      histocompatibility antigens, and they do not develop the CD8+ class I MHC
      restricted cytotoxic T cell subset. We find that these mice are completely
      resistant to B. malayi, indicating that the CD8+ T lymphocyte subset is not an
      obligate requirement for murine resistance to human filarial parasites.

PMID- 1386113
TI  - Nuclear DNA content and nucleation patterns in rat cardiac myocytes from
      different models of cardiac hypertrophy.
AB  - Nuclear DNA content and number of nuclei were examined in cardiac myocytes
      isolated from controls and rats with volume and pressure overload hypertrophy to
      determine if haemodynamic overload alters these nuclear parameters. The
      experimental groups were comprised of normotensive (WKY) and Spontaneously
      Hypertensive rats (SHR). Additionally, Sprague-Dawley rats with aortic
      constriction (AC), pulmonary stenosis (PS), myocardial infarction (MI), and 5
      month arteriovenous fistulas (F) were studied along with appropriate shams for
      each of these groups. Nuclear DNA content was measured from DAPI-stained nuclei
      using an image analysis microdensitometry system. Myocyte volume was measured
      with a Coulter Channelyzer system. Approximately 83% of the left ventricular
      myocytes from the SHR and WKY groups contained a diploid DNA content with the
      remainder being tetraploid. The remaining experimental and sham groups, all
      female Sprague-Dawley rats (SD), were approximately 93% diploid. The nucleation
      patterns differed slightly between rat strains with the SHR/WKY expressing
      approximately 85% binucleation, 14% mononucleation and 5% tri- or
      tetranucleation. All SD groups, control and hypertrophied, showed approximately
      89% binucleation, and 10% mononucleation with the remainder being tri- or
      tetranucleated. In summary: (1) cardiac myocytes from SHR/WKY strains are
      predominantly diploid but to a lesser degree than myocytes from SD; (2) nuclear
      number follows the same pattern with SHR/WKY showing a smaller percentage of
      binucleated myocytes than SD myocytes; (3) neither the duration, severity, or
      type of overload caused a significant change in the extent of polyploidy in
      overloaded hearts from SD rats; and (4) the extent of polyploidy in cardiac
      myocytes from both the right and left ventricles of SHR and WKY animals does not
      differ statistically.

PMID- 1386112
TI  - Preferred antagonist binding state of the NMDA receptor: synthesis, pharmacology,
      and computer modeling of (phosphonomethyl)phenylalanine derivatives.
AB  - A series of substituted [phosphono-, sulfo-, carboxy-, and (N
      hydroxycarbamoyl)methyl]phenylalanines were synthesized as probes for the
      investigation of the preferred antagonist state of the NMDA receptor antagonists.
      The potency of these compounds was evaluated by measuring electrophysiological
      responses induced by NMDA in cultured mouse cortical neurons. 3
      (Phosphonomethyl)phenylalanine [1(m)] a formal AP7 analogue, has been shown to be
      the most potent antagonist in this study with an IC50 of around 5 microM. The
      isomeric 2-(phosphonomethyl)phenylalanine [1(o)] was about half as active as 1(m)
      and as active as compound 5(3), a derivative which is cis-hydrogenated on the
      phenyl ring of 1(m). Replacement of a phosphono by a sulfo group led to a large
      reduction in the ability of these compounds to antagonize NMDA responses,
      although the ortho and meta isomers retained some activity in their reduced
      forms. In both series the para isomers were almost completely inactive at 100
      microM. Introduction of a carboxyl or a bidentate HONHCO group in place of the
      phosphono moiety in the 3-position results in compounds devoid of activity. The
      active and inactive compounds of this study were used in conjunction with the
      most potent linear and cyclic phosphono-containing NMDA antagonists reported to
      date to determine, via computer modeling techniques, a three-dimensional model
      corresponding to a antagonist preferring state of the NMDA binding site. This
      structure defines a pharmacophore which is characterized by (i) well-defined
      distances between the central atoms of the polar groups PO3H-, NHn+, (n = 2, 3),
      and COO- (P-N = 5.89 +/- 0.12 A, P-C = 6.66 +/- 0.08 A, and N-C = 2.28 +/- 0.01
      A), (ii) a sterically allowed region between the C5 methylene and the PO3H-
      group, and (iii) a molecular electrostatic field in which the positive, neutral,
      and negative potential zones are self-contained--with the negative potential zone
      connecting the PO3H- and COO- groups as the largest. We have compared our results
      to a preliminary model of the NMDA antagonist site by Hutchison et al. and to a
      topological model of the NMDA-glycine receptor site by Cordi et al. Our proposed
      steric-electrostatic pharmacophore which refines, simplifies, and improves these
      models has now to be validated by the design of new NMDA antagonists.

PMID- 1386114
TI  - Breast cancer in young women: questions outpace answers.

PMID- 1386115
TI  - Inverse modulation of steady-state messenger RNA levels of two non-integrin
      laminin-binding proteins in human colon carcinoma.
AB  - BACKGROUND: Interactions between cells and the basement membrane glycoprotein
      laminin are altered during colon cancer progression. Colon carcinoma and normal
      mucosa cells express a variety of laminin-binding proteins, including the 67-kd
      laminin receptor (67 LR) and a 31-kd human laminin-binding protein (HLBP31)
      homologous to the 31-kd human IgE-binding protein/galactoside-binding lectin.
      PURPOSE: To investigate whether various laminin-binding proteins are
      differentially expressed in human colon carcinoma, we studied messenger RNA
      (mRNA) levels of the 67 LR and HLBP31 in matched tumor and adjacent normal mucosa
      samples from a series of 21 patients. METHODS: Total cellular RNA from tumor and
      normal mucosa was isolated and analyzed by Northern and slot blot hybridization.
      In addition, HLBP31 protein levels were assessed by the immunoblot technique.
      Quantitative laminin affinity chromatography was also used to measure the
      synthesis of HLBP31 protein in five human cancer cell lines. RESULTS: The steady
      state mRNA level of HLBP31 was downregulated (i.e., decreased) in 18 of 21 human
      colon carcinomas compared with the level in their corresponding normal colonic
      mucosa. On average, the level of HLBP31 mRNA was decreased 50% +/- 30% (+/- SD)
      in the colon cancers. The mean ratio of colon cancer HLBP31 mRNA to adjacent
      normal mucosa HLBP31 mRNA was twofold lower in primary tumors of patients with
      metastases (0.3 +/- 0.2 SD) than in primary tumors of patients free of metastatic
      lesions (0.6 +/- 0.2 SD). The differences between the two groups of patients were
      statistically significant (P less than .05, Wilcoxon-Mann-Whitney test). We have
      previously shown that the ratio of colon cancer 67 LR mRNA to corresponding
      normal mucosa 67 LR mRNA was increased in the same patient population. When the
      two ratios (ratio of cancer to normal HLBP31 mRNA and ratio of cancer to normal
      67 LR mRNA) were compared, HLBP31 mRNA/67 LR mRNA was significantly lower (P less
      than .05) in primary tumors with metastases (mean +/- SD, 0.3 +/- 0.2) than in
      primary cancers without metastases (mean +/- SD, 0.7 +/- 0.5). The steady-state
      level of HLBP31 mRNA was directly correlated with the amount of HLBP31 protein in
      both colon tissue samples and human cancer cell lines. CONCLUSION: HLBP31 mRNA
      expression in colon cancer tissues is modulated inversely to that of 67 LR mRNA
      expression. The down-regulation of HLBP31 appears to be associated with the
      metastatic capabilities of colon cancer cells. IMPLICATIONS: Prospective studies
      on a large cohort should determine if the systematic detection of HLBP31 and 67
      LR protein and/or mRNA can be a valuable adjunct in the prognostic evaluation of
      primary colon cancers.

PMID- 1386116
TI  - Prophylactic antibiotics for the prevention of infectious complications including
      empyema following tube thoracostomy for trauma: results of meta-analysis.
AB  - Since 1977, six clinical trials have been performed on the subject of routine
      antibiotic prophylaxis in patients requiring tube thoracostomy for trauma. No
      definitive conclusions have been reached regarding the efficacy of antibiotic use
      in this setting. The results of these clinical trials were pooled to generate an
      unbiased estimate of the efficacy of antibiotic prophylaxis for tube thoracostomy
      using the technique of meta-analysis. Meta-analysis is a statistical method for
      synthesizing results from separate but similar experiments, grouping them, and
      comparing each to the null hypothesis. Meta-analysis allows synthesis of all of
      the available data on antibiotic prophylaxis for tube thoracostomy to resolve the
      controversy surrounding this issue generated by different but similar clinical
      studies with conflicting results. Despite different conclusions of value when
      taken individually, the combined analysis does not support the null hypothesis
      (no effect of antibiotics). The statistical method is highly significant despite
      different mechanisms of injury, pathologic findings, and antibiotics employed.

PMID- 1386117
TI  - Clinical trials: conflicting opinions.

PMID- 1386118
TI  - The alterations of norepinephrine and acetylcholine concentrations in immature
      rat urinary bladder caused by streptozotocin-induced diabetes.
AB  - The concentrations of norepinephrine (NE) and acetylcholine (ACh) in the body and
      base of the bladder were investigated two, four and eight weeks after the
      administration of streptozotocin to four-week-old rats. At four and eight weeks
      after following dosage, NE concentrations in the base of the bladder of the
      diabetic rats were significantly higher than those of control rats. At the two
      week diabetic condition, ACh concentrations in both the body and base of the
      bladder diabetic rats were about two-fold higher than in the respective control
      levels and remained constant for eight weeks. However, the control rats showed
      dramatic increase in ACh concentration from two to four weeks after dosage. There
      was no significant difference in the response of bladder muscle strips to
      phenylephrine, isoproterenol and ACh in the diabetic vs. control rats throughout
      the experiment. These observations suggest that the alteration of autonomic
      nervous system may occur at an early stage of diabetes mellitus in immature rats
      and that the high concentration of NE in the diabetic bladder base may reflect an
      adaptive overfunction of the adrenergic system probably to maintain continence.
      Furthermore, the lack of change in ACh concentration with age in diabetic rats
      may suggest an impaired development of the cholinergic system.

PMID- 1386119
TI  - [Pharmacology and action mechanism of natriuretic peptide family as a regulator
      of blood pressure].

PMID- 1386120
TI  - [Pharmacology and action mechanism of growth factor as a regulator of blood
      pressure].

PMID- 1386121
TI  - [Etiological and physiopathological significance of atrial natriuretic peptide
      activity in essential hypertension].

PMID- 1386123
TI  - [Cardiac diseases complicated with hypertension].

PMID- 1386122
TI  - [Molecular biology of the natriuretic peptide family].

PMID- 1386124
TI  - [Electrocardiographic findings in hypertensive heart disease--detection,
      prevalence, significance, progression and regression].

PMID- 1386125
TI  - [Quantitative evaluation of hypertensive left ventricular hypertrophy].

PMID- 1386126
TI  - [Mechanism of the development of cardiac hypertrophy in essential hypertrophy].

PMID- 1386127
TI  - [Arrhythmia in hypertension].

PMID- 1386128
TI  - [Heart failure in hypertension].

PMID- 1386129
TI  - IL-1 receptor antagonist inhibits monocyte chemotactic peptide 1 generation by
      human mesangial cells.
AB  - The elicitation of neutrophils and monocytes from the circulation into the
      inflamed glomerulus is a key process in the pathogenesis of proliferative
      glomerulonephritis. The aim of this study was to determine the factors which
      regulate the expression and synthesis of the monocyte specific chemotaxin,
      monocyte chemotactic peptide 1 (MCP-1). Mesangial cells in culture did not
      constitutively express MCP-1, but could be induced to express both MCP-1 mRNA and
      antigenic MCP-1 by either stimulation with IL-1 alpha or TNF alpha, which are
      also stimuli for interleukin 8 (IL-8/NAP-1) expression and release. Pre-treatment
      of mesangial cells with the IL-1 receptor antagonist (IL-1ra) induced dose
      dependent inhibition of both the expression of MCP-1 and IL-8 mRNA as well as the
      release of both chemotactic peptides in response to IL-1 alpha, while the
      receptor antagonist had no significant effect on TNF alpha induced MCP-1 and IL-8
      generation. This study demonstrates that the IL-1 receptor antagonist was four
      times more effective at inhibiting the IL-1 induced expression and release of IL
      8 compared to that of MCP-1. These results suggest that mesangial cell-derived
      MCP-1 may play an important role in the recruitment of monocytes in glomerular
      inflammation and that an IL-1 receptor antagonist may have therapeutic potential
      for the treatment of glomerulonephritis.

PMID- 1386131
TI  - Improved heart failure protection by FK664, a novel positive inotropic agent, in
      dog heart-lung preparations.
AB  - The effects of FK664, a novel positive inotropic agent, and enoximone on
      pentobarbital-induced heart failure were compared in dog heart-lung preparations.
      Both FK664 and enoximone improved the cardiac function curve in a dose-dependent
      manner and restored it to the control level at drug concentrations of 1
      microgram/ml and 10 micrograms/ml, respectively. Therefore, the cardiotonic
      potency of FK664 appears to be 10 times that of enoximone. These agents were
      almost equal in force-rate separation of cardiac effect. Neither of the agents
      produced arrhythmia at any dose tested. These results suggest that FK664 may be a
      potent cardiotonic agent for the treatment of heart failure.

PMID- 1386130
TI  - Serum levels of helper factors (IL-1 alpha, IL-1 beta and IL-6), T-cell products
      (sCD4 and sCD8), sIL-2R and beta 2-microglobulin in patients with B-CLL and
      benign B lymphocytosis.
AB  - Chronic B-lymphocytic leukemia (B-CLL) cells may be regulated by immune
      functions. In an attempt to analyze such functions, helper factors (IL-1 alpha,
      IL-1 beta and IL-6), T-cell products (sCD4 and sCD8) and sIL-2R and beta 2
      microglobulin were measured in serum of patients at different stages of the
      disease. Patients were classified as having monoclonal lymphocytosis of
      undetermined significance (MLUS), stable or progressive B-CLL respectively. A
      significant, but modest, increase of IL-1 alpha was found in B-CLL as well as in
      MLUS patients whereas IL-6 levels were increased in MLUS only. sCD8 levels were
      increased both in MLUS and B-CLL but augmented sCD4 concentrations were found
      statistically significant only in progressive B-CLL. beta 2-microglobulin and sIL
      2R were related to the extent of the monoclonal B-cell fraction. The data
      indicate an increased T-suppressor activity in both MLUS and B-CLL patients and a
      selective increase of helper T-cell activity in progressive B-CLL. A possible
      immunoregulatory influence of helper T cells on disease progression is discussed.

PMID- 1386132
TI  - Characterization of binding of a specific antagonist, [3H]-SQ 29,548, to soluble
      thromboxane A2/prostaglandin H2 (TP) receptors in human platelet membranes.
AB  - Binding of [3H]-SQ 29,548 was characterized to soluble thromboxane
      A2/prostaglandin H2 (TP) receptors from human platelet membranes as a means of
      examining ligand-receptor interactions outside the lipophilic environment of the
      cell membrane. Kinetic determination revealed a rate of ligand-receptor
      association of 1.4 x 10(7) +/- 0.2 M-1 x min-1 and a rate of dissociation of 0.5
      +/- 0.07 min-1. The resultant equilibrium affinity constant was 36.3 +/- 5.8 nM.
      Saturation binding analysis revealed a single class of [3H]-SQ 29,548 binding
      sites with an affinity constant of 39.7 +/- 4.3 nM and a B(max) of 1735.7 +/-
      69.1 fmol/mg protein. Specific [3H]-SQ 29,548 binding was inhibited by specific
      TP receptor antagonists and agonists in a rank order of potency similar to that
      seen in platelet membranes: SQ 33,961 much greater than SQ 29,548 greater than BM
      13,505 greater than or equal to U 46619 greater than BM 13,177. PGD2, PGE2 and
      PGI2 did not appreciably inhibit the specific binding of [3H]-SQ 29,548. These
      data indicate that [3H]-SQ 29,548 binding to soluble human platelet TP receptors
      was specific, saturable, and reversible.

PMID- 1386133
TI  - Nafarelin for endometriosis.

PMID- 1386134
TI  - Microvascular flow vectors in normal and hypertrophic myocardium as determined by
      the method of colored microspheres.
AB  - Sequential in vivo infusion of two differently colored microsphere suspensions
      into the left atrium of normal and hypertrophic rat myocardium revealed that
      certain coronary capillaries contained microsphere aggregates of both colors. A
      capillary flow vector was established based on the sequence of colors embolized
      within each aggregate. Critical examination of flow vectors among neighboring
      capillaries enabled the characterization of capillary flow direction. Results
      indicated a predominance in concurrent flow direction, which decreased
      significantly (P less than 0.001) with capillaries further removed from an
      individual reference capillary. The percentage of concurrent flow was also found
      to be significantly lower in subendocardium (P less than 0.001) than in
      midmyocardium. Cardiac hypertrophy was not a contributing factor to the above
      findings. This study provides previously unattainable data regarding transmural
      capillary flow direction and suggests regional adaptations in coronary
      microvascular flow.

PMID- 1386136
TI  - The causes of low back pain.

PMID- 1386135
TI  - Improvement in outcome for very low birthweight children: apparent or real?
AB  - OBJECTIVE: To determine whether improvement in the survival rate of infants with
      a birthweight of less than 1501 g was accompanied by an increase in the rate of
      neurological impairment or disability among the survivors. DESIGN, SETTING AND
      PATIENTS: Two cohorts of consecutive very low birthweight infants (birthweight
      less than 1501 g) in one tertiary perinatal centre were followed prospectively to
      eight years of age; for both cohorts, comparison groups of children of
      birthweight more than 1501 g were randomly selected from hospital births.
      INTERVENTIONS: The first cohort was born before the introduction of assisted
      ventilation (1966-1970), the second after assisted ventilation was well
      established (1980-1982). MAIN OUTCOME MEASURES: Comparisons between cohorts, at
      eight years of age, of the survival rates and the rates of severe sensorineural
      impairments and disabilities. RESULTS: The survival rate for very low birthweight
      infants to eight years of age almost doubled between these cohorts, from 37.1% to
      67.8% (odds ratio [OR], 3.4; 95% confidence interval [CI], 2.5-4.7; chi 2 = 57.6;
      P much less than 0.0001). The biggest gain was the increase in non-disabled
      survivors at eight years of age, from 52.6% in the first cohort to 80.8% in the
      second cohort (OR, 3.5; 95% CI, 2.2-5.7; chi 2 = 26.7; P less than 0.0001).
      Furthermore, the rate of severe disabilities in survivors fell substantially,
      from 13.6% to 4.1% (OR, 0.31; 95% CI, 0.14-0.69; chi 2 = 8.3; P less than 0.01).
      Of specific impairments, the rate of severe sensorineural deafness fell
      substantially (3.2% to 0%: OR, 0.14, 95% CI, 0.02-0.81; chi 2 = 4.8; P less than
      0.05), as did the rate of severe intellectual impairment (13.0% to 2.7%: OR,
      0.25; 95% CI, 0.11-0.57; chi 2 = 10.7; P less than 0.002). Only the rate of
      cerebral palsy increased, but not significantly (2.6% to 6.8%; OR, 2.6; 95% CI,
      0.89-7.6; chi 2 = 3.0). CONCLUSIONS: It has been possible to improve the survival
      rate of very low birthweight infants over time without increasing the number of
      severely disabled survivors. Whether the long-term outcome for these infants is
      continuing to improve with more recent advances in perinatal care remains to be
      determined.

PMID- 1386137
TI  - [Side effects of drugs on the skin].

PMID- 1386138
TI  - Increasing scientific power with statistical power.
AB  - A survey of basic ideas in statistical power analysis demonstrates the advantages
      and ease of using power analysis throughout the design, analysis, and
      interpretation of research. The power of a statistical test is the probability of
      rejecting the null hypothesis of the test. The traditional approach to power
      involves computation of only a single power value. The more general power curve
      allows examining the range of power determinants, which are sample size,
      population difference, and error variance, in traditional ANOVA. Power analysis
      can be useful not only in study planning, but also in the evaluation of existing
      research. An important application is in concluding that no scientifically
      important treatment difference exists. Choosing an appropriate power depends on:
      a) opportunity costs, b) ethical trade-offs, c) the size of effect considered
      important, d) the uncertainty of parameter estimates, and e) the analyst's
      preferences. Although precise rules seem inappropriate, several guidelines are
      defensible. First, the sensitivity of the power curve to particular
      characteristics of the study, such as the error variance, should be examined in
      any power analysis. Second, just as a small type I error rate should be
      demonstrated in order to declare a difference nonzero, a small type II error
      should be demonstrated in order to declare a difference zero. Third, when ethical
      and opportunity costs do not preclude it, power should be at least .84, and
      preferably greater than .90.

PMID- 1386139
TI  - Effect of antiinflammatory agents on synthesis of MCP-1/JE transcripts by human
      blood monocytes.
AB  - The human monocyte chemoattractant protein (MCP)-1 encoded by the JE gene belongs
      to a family of low molecular weight secretory cytokines with monocyte-stimulating
      activity. JE transcripts are constitutively synthesized by normal and leukemic
      monocytes, as well as mesenchymal cells, including fibroblasts, vascular
      endothelial cells, and smooth muscle cells. Expression of MCP-1/JE is increased
      severalfold upon exposure of cells to recombinant human granulocyte-macrophage
      colony-stimulating factor but is down-regulated when cells are treated with
      lipopolysaccharide (LPS). Given the proinflammatory properties of MCP-1/JE, we
      have examined the modulatory effects of various antiinflammatory agents,
      including indomethacin, dexamethasone, cyclosporin A, and interleukin-4, on
      levels of MCP-1/JE transcripts either constitutively or inducibly expressed by
      human peripheral blood monocytes. Whereas indomethacin had no detectable effect
      on synthesis of MCP-1/JE transcripts and interleukin-4 treatment resulted in only
      a modest increase in steady state JE mRNA levels, exposure of monocytes to
      dexamethasone (DXS) led to a significant (2.5-10-fold) down-regulation of MCP
      1/JE transcript levels. Studies examining the mechanism of down-regulation of JE
      mRNA by DXS indicated that DXS was acting transcriptionally and
      posttranscriptionally, by reducing the transcriptional rate of the MCP-1/JE gene
      and by destabilizing JE mRNA, a process requiring de novo RNA and protein
      synthesis. Although cyclosporin A by itself had no effect on synthesis of JE
      transcripts, it apparently relieved LPS-mediated down-regulation of JE transcript
      levels, by interfering with the destabilizing effect of LPS on JE mRNA. These
      results may provide new information regarding the action of antiinflammatory
      agents on synthesis of endogenous proinflammatory cytokines.

PMID- 1386140
TI  - Nucleotide deletion of T cell receptor V gamma 2 and J gamma 2 coding sequences
      at V gamma 2-J gamma 2 junctions in immature B cell lines.
AB  - Immature B cell lines transformed with a temperature-sensitive mutant of Abelson
      murine leukaemia virus undergo preferentially V gamma 2 to J gamma 2 joinings
      during culture at a non-permissive temperature (39 degrees C). Here we examined
      nucleotide addition and deletion at the V gamma 2-J gamma 2 junctions in these V
      gamma 2 to J gamma 2 joinings, in comparison with the V gamma 2-J gamma 2
      junctional sequences reported previously in T cells. Forty-eight V gamma 2-J
      gamma 2 junctions were PCR-amplified and sequenced. Only three of 48 V gamma 2-J
      gamma 2 junctions had nucleotide addition. The average nucleotide deletion of V
      gamma 2 coding sequences at the V gamma 2-J gamma 2 junctions was 6.9 nucleotides
      in immature B cells and 5.1 nucleotides in T cells (p less than 0.05). Also, the
      average nucleotide deletion of J gamma 2 coding sequences at the V gamma 2-J
      gamma 2 junctions was 3.1 nucleotides in immature B cells and 1.9 nucleotides in
      T cells (p less than 0.01). The average of total number of the deleted
      nucleotides at the V gamma 2-J gamma 2 junctions was 10.0 nucleotides in immature
      B cells and 7.0 nucleotides in T cells (p less than 0.01). No correlation was
      found between the extent of the nucleotide deletion of the V gamma 2 coding
      sequence and that of the J gamma 2 coding sequence at each V gamma 2-J gamma 2
      junction in immature B and T cells. These results demonstrated that nucleotide
      deletion at the V gamma 2-J gamma 2 junctions was significantly wider in immature
      B cells than in T cells.

PMID- 1386141
TI  - Isotypic and clonal variations in the interactions between model monoclonal
      immune complexes and the human erythrocyte CR1 receptor.
AB  - Erythrocytes (E) play a central role in handling circulating immune complexes
      (IC) in primates. E capture IC via complement receptors, type 1 (CR1) which can
      bind to C3b and C4b ligand sites generated on IC during activation of the
      complement cascade. The present study was designed to explore how the
      immunochemical properties of IC affected their interactions with human E. Model
      IC were constructed by combining murine monoclonal anti-dinitrophenyl (DNP)
      antibodies with DNP-bovine serum albumin. A panel of 10 independently-derived
      monoclonal IgG1, IgG2a, IgG2b, IgG3, IgM and IgA antibodies were used to
      construct IC and their interactions with human E were examined in vitro. The data
      reveal that IC constructed with the different monoclonal antibodies differed with
      respect to their rate of binding to E, the peak magnitude of IC binding to E, and
      the rate and extent of IC release from E. IC containing IgG1 antibodies (IgG1
      IC), IgG2a IC, IgG2b IC, and IgA IC all bound rapidly to E, whereas IgG3 IC and
      IgM IC were bound relatively slowly to E. The peak magnitude of IC binding to E
      correlated directly with their binding rate. There was an inverse correlation
      between the antigen/antibody ratio of the IC and the magnitude of IC binding to
      E. The rate of release of the various types of IC from E also differed. IgG2a IC
      and IgG2b IC displayed the most rapid maximum release rates while IgG3 IC had the
      slowest peak release rate. IgM IC and IgA IC were also released relatively slowly
      from E. IgG1 IC had an intermediate release rate. There was no direct correlation
      between the maximum release rate and either the maximum binding rate or the peak
      magnitude of IC binding to E. While there were some clonotypic differences in
      binding and release rates between IC made with different IgG2a, IgG3 and IgM
      antibodies, antibody isotype appears to be of fundamental importance with respect
      to both the binding of IC to E and the release of IC from E. These data indicate
      that the immunochemical properties of IC can profoundly affect their interactions
      with human E and that the panel of IC constructed with monoclonal antibodies can
      serve as a useful model to explore these interactions.

PMID- 1386142
TI  - Purification and characterization of RHP (factor H) and study of its interactions
      with the first component of complement.
AB  - RHP has been purified from the plasma of both normal individuals and patients
      with rheumatoid arthritis (RA). RHP from both these sources was shown to be
      identical with Factor H by reaction with antisera and N-terminal amino acid
      sequence analysis. Factor H, from both normal and RA sera, inhibited the
      solubilization of immune precipitates but did not affect prevention of immune
      precipitation. Factor H was shown to inhibit the haemolytic activity of fluid
      phase C1, but unlike C1-inhibitor, it had little effect on C1 bound to EA (EAC1).
      Factor H was shown to complex with intact C1, to isolated C1q and to the C1r:C1s
      tetramer. However, binding of factor H to C1 did not dissociate the C1
      macromolecule. A C1-Factor H complex was detected in the serum and plasma from
      normal individuals and patients with systemic lupus erythematosus and RA. Serum
      levels of this complex were reduced, by EDTA-treatment of serum and by activation
      of complement by the classical pathway.

PMID- 1386143
TI  - Characterization of transforming growth factor-beta 1 gene expression in porcine
      immune cells.
AB  - We have investigated the regulation of transforming growth factor beta 1 gene
      expression in a variety of porcine immune cell populations, including peripheral
      blood mononuclear cells (PBMC), peripheral blood monocytes, alveolar macrophages
      and lymphoid cells from various swine lymphoid tissues. Using porcine
      transforming growth factor beta 1 cDNA probes in Northern blot assays, messages
      of 2.5 and 3.5 kb TGF beta 1 mRNA were detected in the cells investigated. A
      variety of mitogenic and immunomodulatory substances were examined for their
      ability to induce TGF beta 1 mRNA expression. These include phorbol 12-myristate
      13-acetate (PMA), phytohemagglutinin (PHA), concanavalin A (Con A),
      lipopolysaccharide (LPS), dexamethasone (Dex), tumor necrosis factor (TNF) and
      interleukin (IL)-1 alpha. While low level constitutive expression of TGF beta 1
      mRNA was detected from all cells investigated, PMA treatment of PBMC and alveolar
      macrophages resulted in a more than 10-fold increase in the steady-state level of
      TGF beta 1 mRNA within 2 hr of PMA addition. Also, the effect of opiate drugs,
      methadone (Md) and morphine (Mor), on TGF beta 1 gene expression was determined.
      Cells treated with opiates expressed the same levels of TGF beta 1 mRNA as
      untreated cells. Since TGF beta 1 biological activity can be induced by opiates,
      the regulation of TGF beta 1 gene expression likely involves mechanisms that do
      not cause changes in mRNA levels.

PMID- 1386144
TI  - Differential modulation of complement factor H and C3 expression by TNF-alpha in
      the rat. In vitro and in vivo studies.
AB  - The biosynthesis of alternative regulatory complement protein factor H was
      investigated using both an in vivo rat model and an in vitro rat hepatocyte
      culture system, and compared to that of C3 component. Subcutaneous injection of a
      single dose of 20 micrograms of recombinant murine tumor necrosis factor-alpha
      (rmTNF-alpha) had no effect on factor H liver mRNA levels, while it increased C3
      mRNA levels. In correlation with this, serum factor H levels remained unchanged
      after rmTNF-alpha injection, whereas C3 levels were increased. In contrast in
      vitro studies showed that rmTNF-alpha had no effect on factor H and C3 expression
      by rat hepatocytes. Recombinant human interleukin-1 alpha (rhIL-1 alpha) did not
      alter the expression of factor H, whereas it increased C3 expression, and
      recombinant human interleukin-6 (rhIL-6) stimulated expression of both proteins.
      This study shows that TNF-alpha is not directly responsible for the increased
      levels of factor H observed in vivo during induced inflammation in the rat. Its
      in vivo effect on C3 secretion might be secondary to the TNF-alpha-induced
      release of IL-1 and/or IL-6.

PMID- 1386145
TI  - Preferential location of N-methyl-D-aspartate (NMDA) receptors on postsynaptic
      membranes and on non-noradrenergic nerve terminals of the rat brain cortex.
AB  - The effect of DSP4-induced destruction of noradrenergic neurones on 3H-3-(2
      carboxypiperazine-4-yl)propyl-1-phosphonic acid (3H-CPP) binding to N-methyl-D
      aspartate (NMDA) receptors and on 3H-desipramine (3H-DMI) binding to the neuronal
      noradrenaline carrier was investigated in rat brain cortex buffy coat membranes.
      3H-DMI bound with high affinity to a single site at the neuronal noradrenaline
      carrier (KD = 5.26 +/- 1.67 nmol/l) whereas the binding of 3H-CPP to the NMDA
      receptor was of intermediate affinity (KD = 274 +/- 45 nmol/l). Fourteen days
      after a single-dose treatment with DSP4 (1) the Bmax value for 3H-DMI binding was
      reduced by 74%, (2) the Bmax value for 3H-CPP binding only tended to be decreased
      (by 24%; not statistically significant), (3) the endogenous noradrenaline content
      was reduced by 70% compared to untreated controls and, (4) the absolute amount of
      the NMDA-evoked 3H-noradrenaline overflow but not the fractional release was
      reduced by 55%. It is concluded that in the rat cerebral cortex presynaptic NMDA
      receptors on noradrenergic nerve endings, which have previously been detected in
      release experiments with NMDA on cortical synaptosomes preincubated with 3H
      noradrenaline, cannot be identified in radioligand binding experiments.
      Obviously, the cerebral cortical NMDA receptors are predominantly located on
      postsynaptic neuronal membranes and potentially on non-noradrenergic nerve
      terminals as well.

PMID- 1386146
TI  - Evidence for the presence of regional differences in the calcium antagonist
      receptors in lower urinary tract smooth muscle.
AB  - (+)-[3H]PN 200-100 (a dihydropyridine calcium channel antagonist) was utilized to
      characterize calcium channel binding sites in rabbit bladder dome, bladder base,
      and urethra. Specific binding of (+)-[3H]PN 200-110 to membrane particulates was
      saturable, reversible, linear to protein concentration, and of high affinity. The
      density of (+)-[3H]PN 200-110 binding sites (Bmax values in fmol/mg of protein)
      and the affinity constants for (+)-[3H]PN 200-110 (KD value in pM) in urethra,
      bladder dome and bladder base were 64.1 +/- 7.8 and 179 +/- 31; 21.9 +/- 3.0 and
      213 +/- 36; and 18.8 +/- 4.2 and 140 +/- 28, respectively. Agonists and
      antagonists inhibited (+)-[3H]PN 200-110 binding with Ki values in the following
      rank order: nitrendipine less than nifedipine less than niguldipine much less
      than Bay K 8644 much less than verapamil. Although carbachol-induced contractile
      responses were 20-30 times smaller in muscle strips from urethra than from
      bladder base or bladder dome, KCl-induced contractions were only 3-4 times
      smaller in urethra than in bladder tissues. Nifedipine inhibited carbachol
      induced contractions in urethra, bladder dome, and bladder base by 76%, 64%, and
      60%, respectively, and completely inhibited KCl-induced contractions in all three
      tissues. IC50 values for nifedipine inhibition of both carbachol- and KCl-induced
      contractions were significantly smaller in urethra than in bladder base or
      bladder dome. Nitrendipine, niguldipine and verapamil inhibited urethral
      contractions induced by carbachol and KCl to the same degree as did nifedipine.
      The IC50 values, obtained from functional studies, for calcium channel
      antagonists were in good agreement with Ki values obtained from binding
      studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386147
TI  - Intravascular balloon dilatation therapy for intracranial arterial vasospasm:
      patient selection, technique, and clinical results.
AB  - Patients presenting with symptomatic intracranial arterial vasospasm are now
      being treated by interventional neurovascular techniques in selected cases. From
      a percutaneous transfemoral approach, a custom-designed silicone microballoon can
      be guided through the intracranial vessels, and inflated to dilate the spastic
      vessel(s). This technique has been useful for both focal and diffuse areas of
      spasm. In clinical trials, 28 patients, ranging in age from 15-73 years have been
      treated. A total of 99 vascular territories have been successfully dilated in
      both the anterior and posterior circulations. Clinical improvement following
      treatment was observed in 17 cases (60.7%). Technical complications directly
      related to therapy included 2 cases (7.1%) of vessel rupture. In long term
      clinical follow-up 17 patients (60.7%) had good to excellent outcome, 2 patients
      (7.1%) remained in poor condition, and 9 patients (32.1%) died despite therapy.
      In patients presenting with symptomatic intracranial arterial vasospasm who are
      unresponsive to medical therapy, treatment by balloon angioplasty techniques may
      help to improve cerebral perfusion and clinical outcome of the patient.

PMID- 1386148
TI  - [Lipoprotein (a), a new atherosclerotic risk factor. Blood levels in normal
      pregnancy].
AB  - Serum levels of lipoprotein (a), an important factor of atherosclerotic risk, in
      32 patients during normal pregnancy and puerperium, were evaluated. Our results
      show a significant increase of the level of this lipoprotein (M = 20 mg/dl)
      versus controls (M = 16 mg/dl) during all periods of pregnancy, with a very
      significant increase at week 20th.

PMID- 1386149
TI  - A regulatory burden.

PMID- 1386151
TI  - The effect of laparoscopic ablation or danocrine on pregnancy rates in patients
      with stage I or II endometriosis undergoing donor insemination.
AB  - The effect of treatment on stages I and II endometriosis was evaluated in 61
      women with laparoscopically proven disease who were undergoing therapeutic donor
      insemination. Only treatment cycles completed after diagnostic laparoscopy were
      used for analysis. To evaluate fecundity, we performed life-table analysis on 343
      treatment cycles of therapeutic donor insemination in 67 patients with stage I or
      II endometriosis and compared it with 212 cycles in 43 patients with no female
      infertility factors. Average monthly fecundity and cumulative conception rates
      over six cycles were calculated for each group. A significant difference was
      found when patients with laparoscopically proven normal anatomy were compared
      with those with endometriosis (P = .002). The fecundity did not differ
      significantly between stage I and stage II endometriosis (P greater than .05).
      Neither ablation during laparoscopy nor medical treatment with danocrine improved
      the fecundity of patients with early-stage endometriosis (P greater than .05).

PMID- 1386150
TI  - Effects of the thromboxane-receptor antagonists AH 23848 and BM 13.177 on human
      uteroplacental arteries.
AB  - OBJECTIVE: We studied the effects of the thromboxane (Tx)A2-receptor antagonists
      AH 23848 and BM 13.177 in small isolated human uteroplacental arteries. METHODS:
      Fetal stem villous arteries and maternal intramyometrial arteries were dissected
      from placental specimens and from myometrial biopsies obtained at cesarean or
      from nonpregnant women after hysterectomy. Vascular ring preparations were
      prepared and mounted in organ baths, and isometric tension was recorded. RESULTS:
      AH 23848 produced competitive, concentration-dependent inhibition of responses to
      the TxA2-mimic U46619 in all vessel types tested. Mean (+/- standard error of the
      mean) pA2 values (the negative logarithm of the concentration of antagonist
      needed to double the half maximum response [EC50] value for U46619) were 8.69 +/-
      0.16 in the stem villous arteries, 9.58 +/- 0.33 in intramyometrial arteries from
      term pregnant women, and 9.25 +/- 0.47 in intramyometrial arteries from
      nonpregnant women. In stem villous arteries, the pA2 value for BM 13.177 was 6.15
      +/- 0.13, whereas these values in intramyometrial arteries could not be assessed.
      However, the concentrations needed to produce inhibition of U46619-induced
      contractions were considerably higher for BM 13.177 than for AH 23848. Both drugs
      inhibited responses to prostaglandin (PG)F2 alpha and PGE2 in stem villous
      arteries, while leaving responses to vasopressin in intramyometrial arteries
      unaffected. No differences in the effects of the two antagonists were found
      between intramyometrial arteries from nonpregnant and term pregnant women.
      CONCLUSIONS: Our results suggest that TxA2-receptor antagonists effectively
      inhibit responses to TxA2 in human uteroplacental arteries, and such drugs may
      represent an interesting therapeutic approach in preeclampsia.

PMID- 1386152
TI  - [Kynurenine and its metabolites in nervous system diseases].
AB  - Kynurenine is a metabolite of the tryptophan-nicotine-amide-adenine-dinucleotide
      pathway. Recent preclinical and clinical data suggest that kynurenine and its
      metabolites (kynurenic acid, quinolinic acid) may play important role in the
      pathogenesis of neurological and other disorders (Huntington's disease, epilepsy,
      hypoxia, ulcus, hepatic and infectious diseases). Experimental data and
      theoretical considerations suggest that modification of kynurenine metabolism and
      influence of the concentrations of kynurenine metabolites may be useful
      therapeutic strategies in treatment of several disorders. This review is a
      summary of the pathobiochemical mechanisms and possible therapeutic strategies.

PMID- 1386153
TI  - Standardised method of follow-up assessment of preterm infants at the age of 5
      years: use of the WHO classification of impairments, disabilities and handicaps.
      Report from the collaborative Project on Preterm and Small for gestational age
      infants (POPS) in The Netherlands, 1983.
AB  - A nationwide, prospective study was initiated in The Netherlands in 1983,
      involving 1338 liveborn infants with a gestational age less than 32 weeks and/or
      a birthweight less than 1500 g. Pre- and perinatal data, methods and results of
      follow-up until the corrected age of 2 years have been published previously. In
      this paper, methods of follow-up at the age of 5 years are described. At that
      age, 966 children were alive, of which 927 (96%) were assessed during a home
      visit 2 to 6 weeks after their fifth birthday by three specially trained
      paediatricians. A questionnaire served to collect data on medical history,
      respiratory function, behaviour and socio-economic factors. Standardised tests
      were carried out covering the following 10 areas: congenital malformations,
      neuromotor function, mental development, hearing, visual function, language and
      speech development, behaviour, musculoskeletal system, respiratory tract and ENT
      problems, and growth. The outcome was recorded for separate areas and for the
      child as a whole using the WHO classification of impairments, disabilities and
      handicaps.

PMID- 1386154
TI  - New antagonists of the vasopressin receptor mediated contraction in rat tail
      artery.
AB  - A perfused isolated rat tail artery preparation was employed to study
      antagonistic properties of four newly synthesized arginine-vasopressin (AVP)
      analogues against the V1 receptor. The activity of the agents SCATyr(Me)AVP,
      OCATyr(Me)AVP, OCAAVP and SCAAVP was related to that of a recognized antagonist
      d(CH2)5Tyr(Me)AVP. SCATyr(Me)AVP elicited outstanding antagonistic properties by
      blocking at concentration of 10(-7) M nearly completely the constrictory activity
      of AVP. At concentration of 10(-9) M the agent inhibited the AVP-induced
      constriction of artery about 40 times more effectively than the oxytocin (OXT)
      induced constriction. The results obtained prove the validity of the structure
      activity relationship based search for new potent V1 receptor antagonists.

PMID- 1386155
TI  - Role and responsibilities of the nurse in special education facilities.

PMID- 1386156
TI  - Beneficial effect of the ANF analog A68828 on recovery from ischemic acute renal
      failure.
AB  - We have recently reported that administration of the ANF analog A68828 improves
      renal function in an acute model of postischemic acute renal failure. The current
      investigation examined the question whether a short-term infusion of A68828 can
      attenuate the long-term decrement in renal function following an ischemic event.
      Acute renal failure was induced in male Sprague-Dawley rats (200-250 g) by
      complete occlusion of both renal arteries for 30 min. During the initial 60 min
      following ischemia, vehicle (0.1% BSA in saline), A68828 (10 micrograms/kg/min);
      dopamine (10 micrograms/kg/min); A68828 (10 micrograms/kg/min) plus dopamine (10
      micrograms/kg/min); or ANF[1-28] (0.5 microgram/kg/min) were infused
      intravenously. In vehicle-treated animals, a very large increase in plasma
      creatinine was observed, with peak levels at 2 days postischemia (5.5 +/- 1.2
      mg/dL). A68828 alone, A68828 with dopamine, or ANF[1-28] infusion attenuated the
      rise in plasma creatinine levels by approximately 50% on each day of the study;
      dopamine alone was no different from vehicle-treated controls. Gross histological
      examination of kidneys on the fourth day postischemia revealed that significantly
      less damage occurred only in the group treated with A68828 alone. These results
      indicate that infusion of a reduced-size analog of ANF for a brief period in the
      postischemic kidney improves renal function and lessens tissue damage as
      evaluated several days after the ischemic event. Furthermore, dopamine infusion
      provides no discernable beneficial effect.

PMID- 1386157
TI  - [Disability, vacation and travel--goals of a humane travel culture].
AB  - In our society, holiday-making and travelling have become civic rights.
      Handicapped people however frequently find this "civic right to holiday
      travelling" difficult to implement in the usual manner. Mobility barriers,
      behavioural uncertainty in the social-communicative contact of disabled and non
      disabled people but also financial limitations act as disincentives. It therefore
      is necessary that disabled persons' organizations, non-profit and commercial
      service providers but also the Federal government step-up their involvement in
      this field and get efforts toward improvement started, an endeavour that could be
      coordinated and inspired by the Tourism and People with Disabilities working
      group established in 1989.

PMID- 1386158
TI  - [Independent living skills for physically handicapped students with profound
      disability].
AB  - Traditional educational curricula are inadequate for physically disabled students
      with very severe consequences of disablement, as they are insufficiently geared
      toward building Independent Living skills. Typical of their post-school situation
      nowadays, only few of them are in a position of making a direct transition into
      vocational training. The majority continues to need intensive educational
      therapeutic services. The schools for the physically disabled seek to smoothen
      their transition into adult life by leaving-grade programmes aimed at providing
      opportunities for work-related experience as well as at building coping skills
      for day-to-day living. The work and life preparation programme represents a
      special organizational and didactical conception in this context, where the
      demands of adult life serve as the starting point for developing the learning and
      educational goals to be attained.

PMID- 1386159
TI  - [Patients with severe multiple handicaps in workshops for the handicapped--a
      project of the Berlin Workshops for the Handicapped GmbH (BWB) 4 December 1989 to
      31 May 1990].
AB  - A project had been carried out at Berliner Werkstatten fur Behinderte GmbH (BWB)
      aimed at integrating cerebral palsied persons with very severe, multiple
      disability in a workshop for the disabled. Client workshop readiness had been
      determined on the criteria of social capacity, extraordinary care need at the
      workplace, and economic viability of work. The project, planned to last 6 months,
      had to be discontinued because the 9 disabled persons included in this programme
      refused to cooperate after a short period of time.

PMID- 1386160
TI  - [Analysis of the capacity of handicapped patients in comparison with non
      handicapped patients].
AB  - A catalogue of psychological items has been developed that enables any disabled
      person's job-related abilities as well as the psychological requirements of any
      job to be assessed. With this newly developed instrument, ability profiles of
      slow learners and of non-disabled persons have been drawn up. Structural analysis
      of these data show specific differences in the ability structure of the two
      groups. The results indicate new ways for well-directed, disability-related
      promotion in vocational rehabilitation.

PMID- 1386161
TI  - [The course of rehabilitation in patients with locked-in syndrome].
AB  - On the basis of observations of the course taken by 5 patients with so-called
      Locked-in Syndrome (LIS), the level of functional performance that can be
      achieved by long-term rehabilitation notwithstanding very severe initial symptoms
      is set out. The priority measures in the early phases of the condition and the
      particular problems of long-term rehabilitation are summarized in a checklist.
      Technical aids to ameliorate communication are dealt with in some detail. Special
      importance is attributed to patient-centered psychotherapeutic support and to
      family involvement.

PMID- 1386162
TI  - Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage
      leukemia.
AB  - A t(17;19) chromosomal translocation in early B-lineage acute leukemia was shown
      to result in chimeric transcripts that contain sequences from the E2A basic helix
      loop-helix transcription factor gene on chromosome 19, fused to sequences from a
      previously unidentified gene (HLF) on chromosome 17 that encodes a hepatic
      leukemia factor. The chimeric protein consisted of the amino-terminal
      transactivation domain of E2A linked to the carboxyl-terminal basic region
      leucine zipper domain of HLF. HLF was normally expressed in liver and kidney, but
      not in lymphoid cells, and was found to be closely related to the leucine zipper
      containing transcription factors DBP (albumin D-box binding protein) and TEF
      (thyrotroph embryonic factor), which regulate developmental stage-specific gene
      expression.

PMID- 1386163
TI  - Left ventricular function in congenital heart disease.

PMID- 1386164
TI  - Laparoscopic cholecystectomy in a community hospital setting.
AB  - Recently, laparoscopic cholecystectomy has become the preferred surgical
      procedure for removal of the gallbladder. However, many surgeons believe that the
      safety and efficacy have yet to be proved in the community hospital setting. To
      address this concern, a retrospective chart review of the initial 271 instances
      of inpatient laparoscopic cholecystectomy within a community hospital was
      undertaken. All procedures were performed by 15 general surgeons in private
      practice and residents in general surgery. Of the 271 patients, 11 were converted
      to open cholecystectomy. Surgical complications occurred in six of the 260
      instances of laparoscopic cholecystectomy (2.3 percent), with only one injury to
      the common bile duct. Major postoperative complications occurred in 23 patients,
      including severe postoperative pain (nine patients), prolonged ileus (seven
      patients), bile leakage (three patients), retained common duct stones (two
      patients), respiratory failure (one patient) and postoperative myocardial
      infarction (one patient). The period of hospitalization ranged from one to 64
      nights with a median of one night. The operative mortality rate was zero percent.
      Multivariate analysis identified two factors associated with an increased risk of
      postoperative complications. Patients 70 years of age or older and patients whose
      operating times were greater than one hour and 45 minutes were at increased risk
      for postoperative complications. We believe that these data represent the general
      outcomes of the laparoscopic procedure in a community hospital setting and lend
      support to the argument that the procedure can be performed safely and
      effectively in this setting.

PMID- 1386165
TI  - Tactility.

PMID- 1386166
TI  - Effect of GR32191 and other thromboxane receptor blocking drugs on human platelet
      deposition onto de-endothelialized arteries.
AB  - A range of thromboxane A2 receptor blocking (TxRB) drugs, prostacyclin and
      aspirin have been assessed as inhibitors of human platelet deposition onto rabbit
      and human de-endothelialized arteries in vitro. Platelet deposition was
      quantified by measuring the radioactivity associated with de-endothelialized
      arteries following superfusion with 111indium-labelled human platelets
      reconstituted in blood. Using rabbit aorta, all of the compounds tested produced
      a similar maximum inhibition (approximately 70%) of platelet deposition; from
      scanning EM studies the residual deposition appeared to represent a monolayer of
      adhered platelets. The potency of the TxRB's for inhibiting deposition was
      GR32191 greater than or equal to GR36246 greater than SQ29,548 greater than
      ICI185282 greater than or equal to AH23848 much greater than BM13.177 consistent
      with their TxRB potency on human platelets. Using human umbilical arteries, the
      TxRB's achieved a smaller maximum inhibition of deposition (approximately 50%)
      than did prostacyclin or the fibrinogen receptor blocking peptide Gly-Arg-Gly-Asp
      Ser (GRGDS) (60-75%). In addition, using human umbilical arteries, the
      structurally-related TxRB's GR32191 and GR36246 exhibited a greater than 1000
      fold enhancement in potency as inhibitors of platelet deposition over that seen
      in the rabbit aorta. In preliminary experiments, GR32191 also displayed a similar
      high potency on human cerebral arteries. In contrast, the structurally unrelated
      compounds SQ29,548, ICI185282 and BM13.177 exhibited similar potencies on human
      umbilical arteries to those observed on the rabbit aorta; aspirin and
      prostacyclin also displayed similar potencies on the two preparations. The
      enhanced effect of GR32191 and GR36246 on human umbilical arteries therefore
      appears unrelated to their action as TxRB's on human platelets although the
      mechanism of this unique action is at present unknown. However, if these drugs
      exhibited a similar high potency for preventing mural thrombus formation in vivo
      in man, they may represent a major advance in the treatment of occlusive vascular
      disease.

PMID- 1386167
TI  - Plasmin stimulates the release of dermatan sulfate from vascular smooth muscle
      cells in culture.
AB  - We investigated the effect of plasmin on the release of sulfated
      glycosaminoglycans (GAG) from cultured vascular smooth muscle cells. Confluent
      cultures of vascular smooth muscle cells from bovine aorta were labelled with
      [35S]sulfate and incubated at 37 degrees C for principally 60 min in a serum-free
      medium in the presence of plasmin. Plasmin at 10 mU/ml (approximately 2.7
      micrograms/ml) and above significantly increased the release of [35S]sulfate
      labeled GAG (35S-GAG) from the cell layer after a 60 min incubation. A time
      course study showed that plasmin at 10 mU/ml significantly increased the 35S-GAG
      release after 20 min and longer. However, plasminogen at 100 mU/ml and below did
      not cause a significant change of the 35S-GAG release after a 90 min incubation.
      A characterization of 35S-GAG revealed that plasmin increased both dermatan
      sulfate and the other 35S-GAG in the medium. Plasmin at 100 mU/ml enhanced the
      cell detachment significantly but only slightly. From these results, it was
      suggested that a endogenous thrombin inhibitor heparin cofactor II may be
      activated in the liquid phase by dermatan sulfate released from plasmin
      stimulated vascular smooth muscle cells when the vascular is disrupted and plasma
      is exposed to extravessel.

PMID- 1386168
TI  - Photodynamic therapy.
AB  - The preliminary data suggest that red-light whole-bladder photodynamic therapy is
      safe and effective in the treatment of Tis and may be useful in the prophylactic
      management of superficial bladder cancer. Theoretically, whole-bladder
      photodynamic therapy has the advantage of higher efficacy after a single
      treatment than most conventional modalities for superficial bladder cancer. In
      patients with Tis, the complete response rate is 88%, and 25% have recurrences
      during a mean follow-up of 20 months (range 12-60). In patients undergoing
      prophylaxis, the recurrence rate is 31% and the median time to recurrence is 18
      months. Importantly, none of the high-risk patients treated with whole-bladder
      photodynamic therapy has developed disease progression in stage or grade at the
      time of recurrences. Whole-bladder therapy also has the potential advantage of
      repeat treatment without increased tumor resistance or increased morbidity. Data
      from the present phase II-III clinical trials involving a large number of
      patients will define the role of photodynamic therapy in the management of
      superficial bladder cancer.

PMID- 1386169
TI  - [The cystic duct stump after laparoscopic cholecystectomy].
AB  - The aim of this study was to evaluate the length of cystic-duct stumps after
      laparoscopic cholecystectomy. 113 patients underwent intravenous cholangiography
      2 to 3 months postoperatively, whereby a cystic-duct remnant of up to 1 cm was
      found in 34.5% (n = 39) and between 1 and 2 cm in 36.3% (n = 41). In 24.8% (n =
      28) a stump measuring 2 to 3 cm was registered and in 4.4% (n = 5) the cystic
      duct remnant was more than 3 cm. Possible consequences with regard to the
      development of the postcholecystectomy syndrome are discussed. In our experience
      laparoscopic cholangiography seems to be a useful procedure to detect
      cysticolithiasis and as preliminary measure to undertaking the correct
      therapeutic steps. Adherence of this strategy might avoid possible later
      complications by elimination of their principal cause.

PMID- 1386170
TI  - [Repeated water immersion as an alternative, non-medicamentous treatment concept
      in disordered sodium homeostasis? Studies of circulatory and volume regulation
      with special reference to ANP-dependent sodium excretion in patient with liver
      cirrhosis, arterial hypertension, and healthy probands].

PMID- 1386171
TI  - Injured nurse--walk a mile in my shoes.

PMID- 1386172
TI  - Human helper T cell lines established by coculture of normal human cord
      leukocytes with an HTLV-II-infected rabbit leukocyte cell line (Ra-IIA).
AB  - Three helper T cell lines, designated CR-IIA (CR-IIA-1, CR-IIA-2, and CR-IIA-3),
      were established by coculturing normal human cord leukocytes with a lethally
      irradiated HTLV-II (human T-lymphotropic virus type II)-infected rabbit leukocyte
      cell line (Ra-IIA). CR-IIA had a normal human karyotype and expressed the surface
      markers CD3(+), CD4(+), CD8(-), CD19(-), CD25(+) and HLA-DR(+), confirming their
      helper T cell nature. CR-IIA cells were all free of Epstein-Barr virus nuclear
      antigen and were immunoreactive with serum samples from HTLV-I- or HTLV-II
      infected patients and with anti-HTLV-I, p19 or p24 antibody. The provirus genome
      of HTLV-II was detected in these cell lines by the polymerase chain reaction
      combined with a digoxigenin-enzyme-linked immunosorbent assay. Electron
      microscopy of CR-IIA-1 cells revealed a few immature type C virus particles.
      These results suggest that HTLV-II was transmitted from the infected rabbit
      leukocyte cell line to human cord helper T lymphocytes with the development of
      immortalized HTLV-II-producing T cell lines.

PMID- 1386174
TI  - Postural changes in atrial natriuretic peptide (ANP) and fluid balance in
      conscious goats.
AB  - To gain insight into how weak physiological stimuli suffice to release ANP, the
      effects of 15 degrees head-up and head-down tilt, 90 min each in succession, on
      plasma atrial natriuretic peptide (ANP), plasma cortisol, plasma and urinary Na,
      K and osmolality, plasma proteins and haematocrit were studied in five conscious
      goats before and after 2 wk daily training for the tilting procedure. In the
      trained goats the 15 degrees tilt did not affect the plasma ANP, cortisol or the
      urine excretion significantly. Total plasma proteins decreased significantly. In
      the untrained goats, on the other hand, an increasing trend was observed in the
      plasma ANP and cortisol as well as in the urine Na excretion during the head-up
      tilt. During the head-down tilt, the levels of ANP and Na excretion remained
      elevated. The plasma ANP was significantly increased after 40 min, by 28% as
      compared to the pre-tilting level. The plasma cortisol was first elevated, but
      then returned to the starting level. The results suggest that in the trained
      goats the responses to tilting were unmasked. Despite minor effects of the 15
      degrees tilt in itself, increased plasma ANP seemed to be associated with
      increased natriuresis.

PMID- 1386175
TI  - [Laparoscopic ureterolithectomy. A new option].
AB  - An integral conception of patients with various diseases can benefit from the
      contemporary technological developments which allow to differentiated non
      invasive approaches as diagnostic and therapeutical resources. This kind of
      patient has allowed further development of laparoscopic surgery in urology
      derived from the addition of reported conditions: obstructive prostate carcinoma,
      juxta-vesical gross lithiasis imbedded for 2 years, complexity of ureteroscopic
      access, large volume for extracorporeal lithotripsy and the need to know the
      extend of nodular affectation.

PMID- 1386173
TI  - External calcium sensitivity of low sodium contractures in the control and
      hypertrophied right ventricle of the ferret.
AB  - The existence of possible differences of calcium (Ca2+) fluxes through the
      sarcolemmal sodium-calcium (Na+/Ca2+) exchanger during hypertrophy has been
      tested by comparing the characteristics of the contracture--as an indicator of
      the intracellular Ca2+ concentration--induced by partial or total withdrawal of
      external sodium (Na+), in the absence of external potassium, in the right
      ventricular trabeculae of adult ferret hearts. Pressure-overload was induced by
      pulmonary artery clipping and led to an increase of the right ventricular weight
      of 60%. At an external Ca2+ concentration ([Ca2+]o) of 3 mM, the dependence of
      the contractures on extracellular sodium concentration ([Na+]o), the rate of
      tension development, the time course of spontaneous relaxation and the time
      course for the repriming of the contracture were unchanged by hypertrophy.
      However, the relationship between [Ca2+]o and contracture amplitude at various
      [Na+]o showed that the apparent affinity of the contracture for [Ca2+]o was
      decreased in hypertrophied preparations. Thus, in 0 mM [Na+]o, half-maximal
      contracture was induced at a [Ca2+]o of 0.012 +/- 0.016 mM and 0.171 +/- 0.021 mM
      in control (n = 11) and hypertrophy (n = 12) respectively (P less than 0.001).
      Although these data may be indicative of a decreased Ca2+ influx through the
      Na+/Ca2+ exchanger, it cannot be excluded that intracellular buffering mechanism
      may also be involved in this differential response to [Na+]o withdrawal.

PMID- 1386176
TI  - Conservation of docosahexaenoic acid in the retina.
AB  - Over the last several years, evidence has accumulated that n-3 fatty acids,
      particularly 22:6n-3, are essential for the development of the structure and
      function of the visual system. The importance of 22:6n-3 is reflected in the
      tenacious manner in which the retina conserves this fatty acid during n-3
      deficiency. We have shown that conservation is achieved by recycling 22:6n-3
      within the retina or between the retina and the pigment epithelium. Within the
      retina, recycling could be accomplished by deacylation-reacylation reactions
      (Louie et al., 1991; Zimmerman and Keys, 1988). Recycling between the retina and
      the RPE may be achieved through specific transport proteins, possibly
      interphotoreceptor retinoid-binding protein (Bazan et al., 1985) and/or
      apolipoprotein E (Bazan et al., 1991).

PMID- 1386177
TI  - Docosahexaenoic acid uptake and metabolism in photoreceptors: retinal
      conservation by an efficient retinal pigment epithelial cell-mediated recycling
      process.
AB  - After 18:3 omega 3 is obtained from the diet, it is accumulated by the liver,
      where it is esterified and temporarily stored as triacylglycerols. As it is
      required, 18:3 omega 3 is elongated and desaturated to 22:6 omega 3, then
      released into the circulation with lipoprotein carriers. RPE cells remove the
      22:6 omega 3 from the choriocapillaris and subsequently release it to the retina
      proper. In the frog, all 22:6 omega 3 input to the photoreceptors occurs by way
      of the RPE cells. After passing through the interphotoreceptor matrix, it is
      selectively taken into the myoid region of photoreceptor cells where it is
      immediately activated and esterified onto position 2 (and sometimes also position
      1) of a glycerol molecule. Some phospholipids are passed through the endoplasmic
      reticulum and Golgi apparatus, while others are not. Generally, transport to the
      outer segments seems to be independent of the Golgi apparatus. Addition to rod
      outer segments occurs in two ways: i) a general diffuse pathway, probably common
      to all fatty acids, which rapidly labels the entire outer segment; and ii) a
      specific dense pathway, utilized only by 22:6 omega 3-containing phospholipids,
      which become locked into the matrix of disc membranes along with opsin. There
      appears to be no exchange between these two forms of label. Accumulation of newly
      synthesized basal discs pushes older, 22:6 omega 3-laden discs apically until the
      outer segment tips, high in 22:6 omega 3-phospholipids (the dense form of outer
      segment label), are shed into the RPE cytoplasm. There, as the 22:6 omega 3 fatty
      acids are released from the disc membranes during degradation, a recycling
      mechanism immediately directs these essential fatty acids back into the
      interphotoreceptor matrix, thus conserving this molecule in the retina, and
      permitting it to be again selectively taken up by the photoreceptors for
      photomembrane synthesis. The process of 22:6 omega 3 handling and trafficking by
      the retina is specifically orchestrated around a conservation mechanism that is
      regulated by the RPE cells and that ensures, through a short feedback loop from
      the phagosomes to the interphotoreceptor matrix, adequate levels of 22:6 omega 3
      for photoreceptors at all times.

PMID- 1386178
TI  - NMDA receptor-mediated arachidonic acid release in neurons: role in signal
      transduction and pathological aspects.
AB  - The N-methyl-D-aspartate (NMDA)-sensitive subtype of glutamate receptor, which
      gates Ca(2+)-permeable ion channels, is known for its role in learning and memory
      formation, in the induction of long-term potentiation, and also in seizure
      activity and neurotoxicity. In primary cultures of cerebellar neurons, agonists
      of NMDA receptors induce a dose-dependent release of [3H]arachidonic acid
      ([3H]AA), which is potentiated by activation of the glycine-positive modulatory
      site and inhibited by NMDA receptor antagonists. NMDA receptor-induced [3H]AA
      release is inhibited by quinacrine and partially depends on the presence of
      extracellular calcium. The [3H]AA release is not sensitive, however, to
      pretreatment with pertussis or cholera toxin, which suggests a Ca(2+)-dependent
      activation of phospholipase A2 not employing G proteins. Pretreatment of cultures
      with the natural and semisynthetic sphingolipids GT1b and PKS 3, respectively,
      inhibits NMDA receptor-mediated [3H]AA release. We also demonstrated glutamate
      evoked [3H]AA release from rat hippocampal slices, which is NMDA receptor
      mediated, calcium dependent and sensitive to quinacrine. Arachidonic acid and its
      metabolites have been shown to play a role as second messengers and to modulate
      neuronal activity. Moreover, they are thought to act as transsynaptic modulators
      in the mechanism of NMDA receptor-induced long-term potentiation in the
      hippocampus. Their role in ischemic brain pathology has also been postulated. Our
      experiments on cultured cerebellar granule cells, incubated in a Mg(2+)-free
      medium deprived of glucose and oxygen, demonstrated a time-dependent stimulation
      of [3H]AA release. This release was inhibited by antagonists of NMDA receptors
      and by quinacrine. Stimulation of NMDA-sensitive glutamate receptors and the
      subsequent calcium-mediated activation of phospholipase A2 may play a role in the
      in vivo release of arachidonic acid during brain ischemia. This hypothesis is
      supported by the observation that the enhanced level of thromboxane B2 in the
      gerbil brain after 5 min of global ischemia is reduced by the systemic
      application of either the NMDA antagonist MK-801 or the ganglioside GM1.

PMID- 1386179
TI  - Left ventricular hypertrophy and hypertension.

PMID- 1386180
TI  - Left ventricular hypertrophy and antihypertensive therapy.
AB  - Left ventricular hypertrophy is more common in hypertensive individuals than in
      normotensive persons. Its presence in hypertensive patients is associated with an
      increased incidence of ventricular arrhythmias, myocardial infarction, congestive
      heart failure, stroke and cardiovascular mortality. Echocardiography is more
      sensitive than electrocardiography in detecting left ventricular hypertrophy.
      Echocardiographic evidence of this condition in patients with borderline
      hypertension may identify those who need treatment. Weight reduction and drug
      therapy can prevent or reverse ventricular hypertrophy in hypertensive patients.
      Recent studies suggest that some antihypertensive drugs are more effective than
      others in reducing left ventricular hypertrophy. These agents include beta
      adrenergic blockers, angiotensin converting enzyme inhibitors, calcium channel
      blockers and sympatholytic agents. Although little evidence exists to show that
      reduction of left ventricular mass decreases cardiovascular morbidity and
      mortality, avoidance of antihypertensive agents that may aggravate hypertrophy
      would seem prudent.

PMID- 1386181
TI  - The effect of late patency of the infarct-related coronary artery on left
      ventricular morphology and regional function after thrombolysis.
AB  - The use of early coronary angiography to assess the benefits of coronary patency
      on left ventricular size and function fails to account for subsequent reocclusion
      or spontaneous reperfusion. To investigate the relationship between late vessel
      patency and changes in left ventricular structure and function after
      thrombolysis, echocardiography was performed within 48 hours and at 6 to 12 weeks
      in 30 patients treated with intravenous thrombolysis. Left ventricular
      endocardial surface area index (ESAj; cm2/m2) and extent of abnormal wall motion
      were quantitated in those with a patent (n = 20) and those with an occluded (n =
      10) infarct-related artery on coronary angiography performed 8 +/- 6 days after
      thrombolysis. Mean ESAi increased from (53 +/- 7 to 61 +/- 10 cm2/m2; p less than
      0.02) in the occluded group during the follow-up period but remained unchanged
      (60 +/- 11 to 62 +/- 11 cm2/m2; p = NS) in the patient group. Mean percentage of
      abnormal wall motion decreased in the patent group (27 +/- 16% to 18 +/- 16%; p
      less than 0.01), whereas no significant change was noted in the occluded group
      (20 +/- 13% to 23 +/- 17%; p = NS). Thus coronary patency at days after
      thrombolysis is associated with both improvement in regional left ventricular
      function and attenuated left ventricular dilatation.

PMID- 1386182
TI  - Excimer laser angioplasty in the atherosclerotic rabbit: comparison with balloon
      angioplasty.
AB  - The early and late results of excimer laser angioplasty and balloon angioplasty
      were compared in atherosclerotic rabbit iliac arteries. Immediately after laser
      angioplasty (n = 13) with a bare 600 microns fiber, there was a 33% increase in
      angiographically measured minimum lumen diameter; after balloon angioplasty (n =
      12), there was a 53% increase. Restenosis (defined as loss of at least 50% of the
      gain achieved by angioplasty) occurred in none of six laser-treated rabbits
      studied 1 month later, compared with four of six balloon-treated rabbits (p =
      0.06). Planimetric measurements of cross sections of the arterial wall 1 month
      after angioplasty showed less intimal and medial tissue in laser-treated (1.8 +/-
      0.2 mm2) than in the balloon-treated rabbits (3.0 +/- 0.4 mm2; p less than 0.05).
      Typical thermal effects were absent on microscopic examination of laser
      angioplasty sites. It is concluded that in this animal model, excimer laser
      irradiation results in an immediate increase in lumen diameter comparable with
      balloon angioplasty, but is associated with less residual atheromatous tissue
      than balloon angioplasty and a trend toward a lower rate of restenosis.

PMID- 1386183
TI  - Nonoperative treatment of membranous obstruction of the inferior vena cava by
      percutaneous balloon transluminal angioplasty.
AB  - Percutaneous transluminal angioplasty (PTA) was performed with the Inoue balloon
      catheter in nine patients with membranous obstruction of the inferior vena cava
      (MOVC) between November 1988 and April 1991. There were five men and four women,
      aged 30.8 +/- 8.5 years. Two patients had had previous surgical treatment. Three
      patients had complete and six had incomplete MOVC. The caval pressure below the
      MOVC was 24.0 +/- 5.6 and 11.8 +/- 5.3 mm Hg (p less than 0.0001) before and
      after PTA, respectively. The caval diameter at the site of MOVC increased from
      1.5 +/- 1.7 to 20.3 +/- 2.6 mm (p less than 0.0001), and the maximal caval
      diameter below the MOVC decreased from 28.7 +/- 12.9 to 19.8 +/- 9.9 mm (p =
      0.006), before and after PTA, respectively. One patient died of massive pulmonary
      embolism following successful PTA. All the other eight patients remained
      asymptomatic during an 18.5 +/- 11.5 months (range 3.5 to 32) follow-up period.
      Two-dimensional ultrasonograms showed no recurrence of MOVC. We conclude that PTA
      with the Inoue balloon catheter is an effective and safe alternative to surgical
      treatment of MOVC.

PMID- 1386184
TI  - Changes in left ventricular size, wall thickness, and function in anemic patients
      treated with recombinant human erythropoietin.
AB  - Left ventricular size and function were evaluated in 15 anemic chronic
      hemodialysis patients before and after the administration of recombinant human
      erythropoietin (rHuEPO). All patients were studied with two-dimensional and M
      mode echocardiographic examinations before the initiation of rHuEPO (T1) and at
      28 +/- 7 weeks of rHuEPO therapy (T2). The two-dimensional targeted M-mode
      echocardiographic measurements obtained were: end-diastolic dimension (EDD); end
      systolic dimension (ESD); stroke dimension (SD); dimensional shortening (SD/EDD);
      systolic posterior wall thickness (PWs); diastolic posterior and interventricular
      septal thickness; end-systolic wall stress (ESWS); and left ventricular mass.
      Mean hematocrit in these patients increased almost 50%. The EDD decreased from a
      mean value (+/- SEM) of 6.41 +/- 0.33 to 4.93 +/- 0.21 cm (p less than 0.05). ESD
      decreased from a mean value of 4.16 +/- 1.2 to 2.77 +/- 0.06 cm (p less than
      0.05). The calculated mean SD decreased slightly but not significantly from 2.21
      +/- 0.69 to 2.19 +/- 0.60 cm. The calculated SD/EDD increased from a mean 0.35 +/
      0.09 to 0.44 +/- 0.07 (p less than 0.05). ESWS fell from 59.2 +/- 12.2 to 37.6
      +/- 9.3 gm/cm2 (p less than 0.01), and left ventricular mass fell (p less than
      0.05) from 347 +/- 15.2 to 227 +/- 59 gm. There was no significant difference in
      resting heart rate or systolic blood pressure between T1 and T2. The increase in
      dimension shortening reflects afterload reduction, as indicated by the fall in
      end-systolic wall stress.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386185
TI  - Long-term fate of isolated congenital absent pulmonary valve.

PMID- 1386186
TI  - Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis.
AB  - Studies designed to examine effects of weight reduction by dieting on total
      cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), very-low-density-lipoprotein cholesterol (VLDL
      C), and triglycerides (TGs) have reported inconsistent results. The purpose of
      this study was to quantify effects of weight loss by dieting on lipids and
      lipoproteins through the review method of meta-analysis. Results from the 70
      studies analyzed indicated that weight reduction was associated with significant
      decreases (P less than or equal to 0.001) and correlations (P less than or equal
      to 0.05) for TC (r = 0.32), LDL-C (r = 0.29), VLDL-C (r = 0.38), and TG (r =
      0.32). For every kilogram decrease in body weight, a 0.009-mmol/L increase (P
      less than or equal to 0.01) in HDL-C occurred for subjects at a stabilized,
      reduced weight and a 0.007-mmol/L decrease (P less than or equal to 0.05) for
      subjects actively losing weight. Our results indicate that weight reduction
      through dieting can be a viable approach to help normalize plasma lipids and
      lipoproteins in overweight individuals.

PMID- 1386187
TI  - Cooperative activation of myosin by light chain phosphorylation in permeabilized
      smooth muscle.
AB  - The purpose of this study was to determine the quantitative relationship between
      the number of myosin molecules that increase their ATPase activity and the degree
      of myosin light chain phosphorylation in smooth muscle. Single turnover
      experiments on the nucleotide bound to myosin were performed in the permeabilized
      rabbit portal vein. In the resting muscle, the rate of exchange of bound
      nucleoside diphosphate was biphasic and complete in approximately 30 min. When
      approximately 80% of the myosin light chain was thiophosphorylated, the
      nucleoside diphosphate exchange occurred at a much faster rate and was almost
      complete in 2 min. Thiophosphorylation of 10% of the myosin light chains caused
      an increase in the rate of ADP exchange from much more than 10% of the myosin
      subfragment-1. Less than 20% thiophosphorylation of the total myosin light chains
      resulted in the maximum increase in ADP exchanged in 2 min. It appears that a
      small degree of myosin light chain phosphorylation cooperatively turns on the
      maximum number of myosin molecules. Interestingly, even though less than 20%
      thiophosphorylation of the myosin light chain caused the maximum exchange of ADP
      within 2 min, higher degrees of thiophosphorylation were associated with further
      increases in the ATPase rates. We conclude that a small degree of myosin light
      chain thiophosphorylation cooperatively activates the maximum number of myosin
      molecules, and a higher degree of thiophosphorylation makes the myosin cycle
      faster. A kinetic model is proposed in which the rate constant for attachment of
      unphosphorylated cross bridges varies as a function of myosin light chain
      phosphorylation.

PMID- 1386188
TI  - Response of slow and fast muscle to hypothyroidism: maximal shortening velocity
      and myosin isoforms.
AB  - This study examined both the shortening velocity and myosin isoform distribution
      of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid
      conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two
      groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative
      contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased
      in response to the hypothyroid treatment. The effects were such that the
      hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms
      while repressing native intermediate myosin and type IIA MHC. In the plantaris,
      the relative content of native SM and type I MHC isoforms increased from 5 to 13%
      and from 4 to 10% of the total myosin pool, respectively. Maximal shortening
      velocity of the soleus and plantaris as measured by the slack test decreased by
      32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal
      shortening velocity as estimated by force-velocity data decreased only in the
      soleus (-19%). No significant change was observed for the plantaris.

PMID- 1386190
TI  - Alloxan, but not streptozotocin, increases blood perfusion of pancreatic islets
      in rats.
AB  - It has recently been shown that selective B-cell toxins alloxan and
      streptozotocin (STZ) possess marked effects also on the vascular system. To
      evaluate to what extent changes in blood perfusion of islets induced by alloxan
      or STZ could be of importance for diabetogenic action of these compounds, we
      first investigated acute effects of alloxan (75 mg/kg body wt iv) and STZ (40
      mg/kg body wt iv) on both whole pancreatic blood flow (PBF) and islet blood flow
      (IBF) in adult rats. Alloxan caused a marked increase in IBF, which was most
      pronounced 3 min after administration and remained for 30 min. PBF, however, was
      decreased 3 min after alloxan administration but was similar to that of control
      animals from 10 min and onward. These two opposite effects on IBF and PBF caused
      the fraction of whole PBF diverted through islets to increase from approximately
      10 to 50%. Pretreatment with glucose (2 g/kg body wt iv), indomethacin (3.5 mg/kg
      body wt iv), dimethyl sulfoxide (10 ml/kg body wt ip of a 33% solution),
      superoxide dismutase (SOD, 1,000 kU/kg body wt iv), NG-methyl-L-arginine (30
      mg/kg body wt iv), theophylline (7 mg/kg body wt iv), or terbutaline (1 mg/kg
      body wt iv) failed to affect stimulation of IBF by alloxan observed at 3 min. SOD
      was found to exert a marked stimulation of IBF both when given alone and together
      with alloxan. Alloxan increased IBF and decreased PBF also in a syngeneic
      pancreaticoduodenal graft in rats but did not affect flow distribution in a
      perfused pancreas-duodenum preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386189
TI  - Differences in regulation between nuclear and cytoplasmic Ca2+ in cultured smooth
      muscle cells.
AB  - The free Ca2+ concentrations in the nucleus ([Ca2+]n) and cytoplasm ([Ca2+]c) of
      cultured smooth muscle cells were estimated using the fluorescent dye indo-1 and
      the ACAS 570 confocal laser microscope. In resting DDT1MF2 smooth muscle cells
      [Ca2+]n was found to be lower than [Ca2+]c. Both values increased transiently in
      response to histamine (100 microM), but during this stimulation [Ca2+]n exceeded
      [Ca2+]c. Maximal increase of [Ca2+]n was observed in the center of the nucleus,
      and a maximal increase of [Ca2+]c was observed in the immediate vicinity of the
      plasma membrane. A similar response was obtained with other agonists, such as
      carbachol or ATP. Comparable results with ATP were obtained in cultured aorta
      cells. The differential rise of [Ca2+]n over [Ca2+]c in DDT1MF2 cells did not
      occur during either spontaneous release of Ca2+ or Ca2+ release induced by
      caffeine (7.5 mM). The differential rise during histamine stimulation was
      abolished by the presence of the intercalating substance ethidium bromide.
      Thapsigargin, a presumed specific inhibitor of the endoplasmic reticulum Ca(2+)
      Mg(2+)-adenosine-triphosphatase, abolished the Ca2+ gradient between nucleus and
      cytosol at rest. During subsequent histamine stimulation the Ca2+ increase was
      largely blocked in both compartments and attained similar levels. We propose that
      the lower value of [Ca2+]n at rest is dependent on an active Ca2+ extrusion
      system. The differential rise of [Ca2+]n over [Ca2+]c during agonist stimulation
      can be explained by an influx of Ca2+ from perinuclear stores and/or by a release
      of intranuclear Ca2+ possibly mediated by a process dependent on the inositol
      lipid metabolism.

PMID- 1386191
TI  - cDNA sequence and tissue expression of bovine vacuolar H(+)-ATPase M(r) 70,000
      subunit.
AB  - cDNA clones encoding the 70,000 relative molecular weight (M(r)) subunit of the
      bovine vacuolar proton-adenosine triphosphatase (H(+)-ATPase) were isolated, and
      a total length of 3.1 kb in overlapping clones from bovine kidney and brain
      libraries was sequenced. The cDNA contains a 1.9-kb coding region and yields a
      deduced protein sequence of 618 amino acids. The subunit sequence has 50% amino
      acid identity with the corresponding subunit from yeast, carrot, and Neurospora
      vacuolar H(+)-ATPases. The internal regions of the protein are most highly
      conserved, whereas the NH2- and COOH-terminals exhibit variability. mRNA levels
      of the M(r) 70,000 subunit were examined in multiple bovine tissues and were
      found to be expressed at highest levels in kidney medulla and cortex, at moderate
      levels in brain and adrenal gland, and at low levels in liver, muscle, and heart.

PMID- 1386192
TI  - Localization of mRNAs coding for isozymes of plasma membrane Ca(2+)-ATPase pump
      in rat kidney.
AB  - We have studied localization of mRNAs coding isozymes of rat plasma membrane
      Ca(2+)-adenosinetriphosphatase pump (rPMCA) in the rat kidney, with use of
      reverse transcription (RT) with subsequent amplification by polymerase chain
      reaction (PCR). When zones of the kidney were separated by macrodissection, a
      large amount of mRNA coding isozyme rPMCA1 was found in all zones; mRNA for
      isozyme rPMCA2 was abundant in cortex and in outer medulla, and mRNA for isozyme
      rPMCA3 was prominent in outer medulla. The mRNAs were analyzed in microdissected
      cortical nephron segments by use of RT-PCR approach described previously [T.
      Moriyama, H. R. Murphy, B. M. Martin, and A. Garcia-Perez. Am. J. Physiol. 258
      (Renal Fluid Electrolyte Physiol. 27): F1470-F1474, 1990]. We detected mRNA for
      isozyme rPMCA2 in microdissected distal convoluted tubules (DCT) and in cortical
      thick ascending limbs (CTAL) and, less consistently, also in proximal convoluted
      tubule and in glomeruli. The mRNA for isozyme rPMCA1 was abundant in glomeruli
      but was absent in all examined cortical tubular segments. Our results document
      that mRNAs for all three major isozymes of rPMCA are present and show a unique
      distribution in the three major zones of rat renal parenchyma. Specific mRNA
      coding for rPMCA2 was detected in cortical tubules, namely in CTAL and DCT,
      whereas mRNA coding isozyme rPMCA1 was found in glomeruli. We suggest that
      isozyme rPMCA2 might be specifically related to epithelial cells and their
      function, whereas rPMCA1 is probably a component of nonepithelial cells including
      these in glomeruli.

PMID- 1386193
TI  - Left ventricular diastolic and systolic performance during chronic experimental
      aortic regurgitation.
AB  - To study the time course of left ventricular structural and functional responses
      to chronic aortic regurgitation, aortic regurgitation was surgically induced in
      rabbits, and Doppler echocardiography was performed preoperatively and serially
      postoperatively for up to 2.5 yr. Twenty-five New Zealand White rabbits underwent
      surgical induction of aortic regurgitation and 13 control animals underwent sham
      operation. Left ventricular endocardial and epicardial surfaces were digitized
      from M-mode echocardiograms to measure the rates of change of cavity dimensions
      and wall thicknesses during diastolic relaxation and systolic contraction. Aortic
      regurgitant animals developed left ventricular dilatation and eccentric
      hypertrophy that remained relatively stable throughout the follow-up period.
      Compared with baseline values, left ventricular mass increased 120% and left
      ventricular internal dimension at end diastole increased 40%, whereas posterior
      wall thickness at end diastole and fractional shortening remained relatively
      stable. Left ventricular diastolic performance was enhanced at 6 mo after
      operation, a finding associated with increased volume load and heart rate
      following induction of aortic regurgitation. Diastolic performance was then
      reduced at 12 mo after operation and demonstrated no further decline throughout
      the remainder of the follow-up period. In contrast, left ventricular systolic
      performance was not altered following operation and remained preserved until the
      final assessment at up to 2.5 yr. Thus alterations in diastolic performance
      occurred without impairment of systolic performance during long-term follow-up of
      chronic experimental aortic regurgitation.

PMID- 1386194
TI  - Are there clinical differences between familial and nonfamilial Alzheimer's
      disease?
AB  - OBJECTIVE: The purpose of the study was to determine whether there are
      differences in clinical characteristics in two groups of patients with
      Alzheimer's disease, those reported to have a family history of dementia and
      those without a family history of dementia. METHOD: Using a data set from an
      Alzheimer's disease patient registry, funded as part of a National Institute on
      Aging cooperative agreement, the authors made comparisons of sociodemographic and
      clinical variables in a group of 462 patients with Alzheimer's disease, 172
      reported to have at least one first-degree relative with dementia and 290
      classified with no family history. RESULTS: Patients with a presumptive family
      history differed from those without a family history in two ways: the course of
      dementia was described as having a fast rather than a slow progression from onset
      of symptoms to diagnosis, and caregivers reported a higher prevalence of family
      history of psychiatric disorders. There were no significant differences in age at
      onset, duration, female gender, aphasia and apraxia, handedness, family history
      of Down's syndrome, or number of children, brothers, and sisters. CONCLUSIONS:
      The association of faster course and family history of psychiatric disorders in
      the patients with a family history of dementia is consistent with the hypothesis
      of heterogeneity, but the overall results could also be explained by a genetic
      environmental model of Alzheimer's disease.

PMID- 1386195
TI  - The quality of life in the year before death.
AB  - OBJECTIVES: Most Americans wish to live a long healthy life, but fear disease and
      dependency in their last years. Until recently, little has been known about the
      prevalence of opposite extremes of health in old age, particularly in the period
      leading up to death. METHODS: We used results from the 1986 National Mortality
      Follow-back Survey to estimate proportions of elderly decedents who were "fully
      functional" or "severely restricted" in the last year of life. Estimates were
      based on responses from proxies to questions regarding the decedent's functional
      status, mental awareness, and time spent in institutions. RESULTS: Approximately
      14% of all decedents aged 65 years and older were defined as fully functional in
      the last year of life; 10% were defined as severely restricted. Proportions
      varied with the decedent's age and sex, the underlying cause of death, and the
      presence of other preexisting conditions. CONCLUSIONS: Results from this survey
      and future surveys can be used to learn more about "successful agers"--their
      medical histories, their life-styles, and whether their relative number is
      increasing or decreasing overtime.

PMID- 1386196
TI  - Clavicular nonunion. Complication with the use of mersilene tape.

PMID- 1386197
TI  - Failure of intragastrically administered Yersinia pestis capsular antigen to
      protect mice against challenge with virulent plague: suppression of fraction 1
      specific antibody response.
AB  - We evaluated the Yersinia pestis capsular (fraction 1 [F1]) antigen as a
      potential oral immunogen in mice. We found that single doses of as much as 0.4 mg
      of F1, administered by intragastric (ig) intubation, were unprotective and did
      not stimulate production of detectable levels of specific antibody. Three weekly
      ig doses resulted in low serum antibody levels that also did not provide
      protection against challenge with virulent Y. pestis. Assays of type-specific
      antibody following intubation and subsequent challenge with a subcutaneous
      inoculation of F1 revealed that the quantity of antigen intubated and the
      secondary IgG2a antibody levels were inversely related, suggesting the induction
      of tolerance to intragastrically administered F1 antigen. Transfer of spleen
      cells from intubated mice to F1 immune recipients failed to demonstrate
      suppression of specific antibody, indicating that the immune tolerance observed
      in intubated mice was not due to a T suppressor cell-mediated effect. The results
      of this study indicate that Y. pestis F1 antigen is not likely to be an
      efficacious immunogen for oral vaccination of mice against plague.

PMID- 1386198
TI  - Adjunctive intraoperative linear extrusion (Fogarty-Chin) balloon angioplasty.
AB  - Eighty-nine patients with 94 stenotic segments (mostly iliac or femoral)
      underwent balloon angioplasty with the first-generation (no guidewire) linear
      extrusion (Fogarty-Chin) system, in an adjunctive mode, and the overall long-term
      patency rate (mean follow-up: 21 months) was 81%. Patients were grouped into
      those having iliac or superficial femoral artery (SFA) lesions and subdivided
      according to the length of lesions. The overall primary and late success rates
      for iliac lesions were 95% and 86%, respectively, and for SFA lesions 91% and
      76%, respectively. The primary and late success rates for iliac lesions less than
      2 cm were 100% and 96%, respectively, and for iliac lesions 2 cm to less than 5
      cm 92% and 80%, respectively. The primary and late success rates for SFA lesions
      less than 2 cm were 100% and 100%, respectively; for lesions 2 cm to less than 5
      cm 100% and 83%, respectively; and for lesions 5 to 10 cm 83% and 67%,
      respectively. A stratified analysis by vessel and segment length reveals that, in
      SFA lesions with a segment length greater than 5 cm, there is a significantly
      lower patency rate (67%) when compared with the combined results of the Fogarty
      Chin balloon angioplasty system in iliac and femoral artery lesions less than 5
      cm (92%). In comparing the composite results presented in a recent text on
      endovascular surgery by Moore and Ahn as the base data for the standard coaxial
      (Gruntzig) balloon system, our results (short and long term) are similar.

PMID- 1386199
TI  - [Extensive iliac atheromectomy as a complement to hyperemization surgery].

PMID- 1386200
TI  - Microbiology, infection control, immunizations, and infectious disease exposure:
      education and practices in United States nursing schools.
AB  - BACKGROUND: Previous data suggest that nursing students in the United States are
      inadequately protected against hepatitis B. This survey focused on the
      immunization and education practices, infection control knowledge, and follow-up
      to infectious disease exposure by U.S. nursing schools. METHODS: To ascertain
      education requirements, immunization practices, and infectious disease
      postexposure follow up, a survey was sent to the director or dean of 1164 U.S.
      nursing schools. RESULTS: Seven hundred sixty-five schools (65.7%) responded to
      the survey. A microbiology course was required before clinical experience by 49%
      of schools. Clinical experience in the operating room was given by 16%, 65% of
      schools offered infectious and communicable disease courses, and 98% offered
      universal precaution instructions. The hepatitis B vaccine was required by 11%;
      2% required yearly influenza vaccination. In a comparison of programs, the
      diploma schools were more likely to have written policies for infectious disease
      exposure follow-up and to use appropriate agencies for exposure follow-up (p =
      0.0001). CONCLUSIONS: A microbiology course before clinical experience should be
      encouraged. Immunization policies and infectious disease exposure follow-up are
      currently inadequate in U.S. associate degree and baccalaureate nursing programs.

PMID- 1386201
TI  - Huntington's disease and neurotoxins.

PMID- 1386202
TI  - Pharmacologic properties of NMDA receptors.

PMID- 1386203
TI  - Differential effect of excitotoxins in the basal forebrain on choline
      acetyltransferase activity in the cortex and amygdala.

PMID- 1386204
TI  - Pharmacologic modulation of MPTP toxicity: MK 801 in prevention of dopaminergic
      cell death in monkeys and mice.

PMID- 1386205
TI  - Hypoxic neurodegeneration in culture: calcium influx, electron microscopy, and
      neuroprotection with excitatory amino acid antagonists.

PMID- 1386207
TI  - Neuropathologic features of Parkinson's, Huntington's, and Alzheimer's diseases.
AB  - Some of the similarities and differences between the neuropathology of
      Parkinson's disease, Huntington's disease, and Alzheimer's disease have been
      reviewed, and the relationship between the three diseases has been discussed.
      Although interconnected and reciprocally innervated structures are affected in PD
      and HD, they appear less closely related than in PD and AD. Different neurotoxins
      may play a part in their pathogenesis, as also suggested from other evidence.
      Neuropathologic features of PD, HD and AD are entirely compatible with a role for
      neurotoxins in their pathogenesis, but do not by themselves make a strong case
      for a neurotoxic hypothesis. However, additional neuropathologic studies of
      experimental neurotoxins may further strengthen arguments in favor of a
      neurotoxic etiology, as the MPTP animal model is doing for Parkinson's disease.
      Such experimental studies along with further molecular biological and other
      sophisticated new methods may open the way for exciting new developments in the
      near future.

PMID- 1386206
TI  - A slow voltage-dependent increase in N-methyl-D-aspartate open-channel
      probability.

PMID- 1386208
TI  - Posttranscriptional regulation of calcitonin/CGRP gene expression.

PMID- 1386209
TI  - A follow-up study of isolated cases of suspected Huntington's disease.
AB  - We reviewed 49 patients in whom a diagnosis of Huntington's disease (HD) seemed
      possible on clinical grounds, but who gave no history of definitely affected
      relatives. In 32 with the typical clinical features of HD (progressive chorea and
      dementia, postural instability, abnormal initiation of saccadic eye movements),
      the diagnosis was confirmed in 7 patients who had had autopsies, affected
      relatives were found in 5 others, and HD remained probable in a further 13 who
      were reexamined. In the 17 with a less typical clinical picture, a diagnosis of
      HD appeared most likely in 2; other causes for chorea such as cerebrovascular
      disease, neuroacanthocytosis, recrudescence of Sydenham's chorea, and drug
      induced tardive dyskinesia could be invoked in the remainder. We conclude that
      the likelihood of HD in a patient with the typical clinical features of this
      disorder but no history of affected relatives is at least 75%, which for
      practical purposes implies a risk to their children hardly less than in familial
      HD. The most plausible explanations for seemingly sporadic patients with HD are
      nonpaternity and mild, late-onset disease that is overlooked by other family
      members.

PMID- 1386210
TI  - Electroconvulsive therapy treatment of depression in a patient with adult GM2
      gangliosidosis.
AB  - Adult GM2 gangliosidosis is a rare disorder that often presents with both
      neurological and psychiatric syndromes. Effective treatment of the psychotic and
      affective symptoms associated with this disorder has been complicated by poor
      treatment response and the concern that many psychotropic agents may worsen the
      underlying gangliosidosis. We report the successful use of electroconvulsive
      therapy for treatment of severe depression in a young man with adult GM2
      gangliosidosis.

PMID- 1386211
TI  - Comparative acid tolerances and inhibitor sensitivities of isolated F-ATPases of
      oral lactic acid bacteria.
AB  - pH activity profiles and inhibitor sensitivities were compared for membrane
      ATPases isolated from three oral lactic acid bacteria, Lactobacillus casei ATCC
      4646, Streptococcus mutans GS-5, and Streptococcus sanguis NCTC 10904, with,
      respectively, high, moderate, and low levels of acid tolerance. Membranes
      containing F1F0 ATPases were isolated by means of salt lysis of cells treated
      with muralytic enzymes. Membrane-free F1F0 complexes were then isolated from
      membranes by detergent extraction with Triton X-100 or octylglucoside. Finally,
      F1 complexes free of the proton-conducting F0 sector were obtained by washing
      membranes with buffers of low ionic strength. The pH activity profiles of the
      membrane-associated enzymes reflected the general acid tolerances of the
      organisms from which they were isolated; for example, pH optima were
      approximately 5.5, 6.0, and 7.0, respectively, for enzymes from L. casei, S.
      mutans, and S. sanguis. Roughly similar profiles were found for membrane-free
      F1F0 complexes, which were stabilized by phospholipids against loss of activity
      during storage. However, profiles for F1 enzymes were distinctly narrower,
      indicating that association with F0 and possibly other membrane components
      enhanced tolerance to both acid and alkaline media. All of the enzymes were found
      to have similar sensitivities to Al-F complexes, but only F1F0 enzymes were
      highly sensitive to dicyclohexylcarbodiimide. The procedures described for
      isolation of membrane-free F1F0 forms of the enzymes from oral lactic acid
      bacteria will be of use in future studies of the characteristics of the enzymes,
      especially in studies with liposomes.

PMID- 1386213
TI  - Identification of a 14-kDa laminin binding protein (HLBP14) in human melanoma
      cells that is identical to the 14-kDa galactoside binding lectin.
AB  - The carbohydrate moieties present on laminin play a crucial role in the multiple
      biological activities of this basement membrane glycoprotein. We report the
      identification of a human laminin binding protein with an apparent molecular mass
      of 14 kDa on sodium dodecyl sulfate-polyacrylamide gels that was found, after
      purification and amino acid microsequencing, to be identical to the previously
      described 14-kDa galactoside binding soluble L-14 lectin. We have designated this
      human laminin binding protein as HLBP14. HLBP14 was purified from human melanoma
      cells in culture by laminin affinity chromatography and gel electroelution. We
      demonstrate that HLBP14 binds specifically to the poly-N-acetyllactosamine
      residues of murine laminin and does not bind to other glycoproteins that do not
      contain such structures, such as fibronectin. HLBP14 was eluted from a murine
      laminin column by lactose, N-acetyllactosamine, and galactose but not by other
      control saccharides, including glucose, fucose, mannose, and melibiose. It did
      not bind to laminin treated with endo-beta-galactosidase. Lactose also eluted
      HLBP14 off a human laminin affinity column, implying that human laminin also
      contains poly-N-acetyllactosamine residues. On immunoblots, polyclonal antibodies
      raised against HLBP14 recognized HLBP14 as well as 31- and 67-kDa molecules that
      are also laminin binding proteins, indicating that these proteins share common
      epitopes. L-14, a dimeric lactose binding lectin, is expressed in a wide variety
      of tissues. Although the expression of this molecule has been linked to a variety
      of biological events, the elucidation of its specific functions has been elusive.
      The observation that HLBP14, a human cancer cell laminin binding protein, is
      identical to L-14 strongly suggests that the functions attributed to this lectin
      could be mediated, at least in part, through its ability to interact with the
      poly-N-acetyllactosamine residues of laminin. HLBP14 could potentially play a
      role during tumor invasion and metastasis by modulating the interactions between
      cancer cells and laminin.

PMID- 1386212
TI  - Rapid method for separation of bacterial DNA from humic substances in sediments
      for polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) was used to amplify an Escherichia coli 16S
      ribosomal gene fragment from sediments with high contents of humic substances.
      Total DNA was extracted from 1 g of E. coli seeded or unseeded samples by a rapid
      freeze-and-thaw method. Several approaches (use of Bio-Gel P-6 and P-30 and
      Sephadex G-50 and G-200 columns, as well as use of the Stoffel fragment) were
      used to reduce interference with the PCR. The best results were obtained when
      crude DNA extracts containing humic substances were purified by using Sephadex G
      200 spun columns saturated with Tris-EDTA buffer (pH 8.0). Eluted fractions were
      collected for PCR analyses. The amplified DNA fragment was obtained from seeded
      sediments containing fewer than 70 E. coli cells per g. Because only 1/100 of the
      eluted fractions containing DNA extracts from 70 cells per g was used for the
      PCR, the sensitivity of detection was determined to be less than 1 E. coli cell.
      Thus, DNA direct extraction coupled with this technique to remove interference by
      humic substances and followed by the PCR can be a powerful tool to detect low
      numbers of bacterial cells in environmental samples containing humic substances.

PMID- 1386214
TI  - Differential scanning calorimetric investigation of pea chloroplast thylakoids
      and thylakoid fractions.
AB  - High sensitivity differential scanning calorimetry (DSC) was employed to study
      the thermal denaturation of components of pea chloroplast thylakoid membranes. In
      contrast to previous reports utilizing spinach thylakoids, several transitions
      are reversible, and deconvolution of the calorimetric curves indicates nine
      transitions in both first and second heating scans, but overlapping transitions
      obscure at least three transitions in the first heating scans of control
      thylakoids. Glutaraldehyde fixation increases the denaturation temperature of
      several transitions which is consistent with a reported increase in thermal
      stability of thylakoid function due to fixation. Acidic pH treatment has little
      effect on the DSC curves, although it has been reported to have a significant
      effect on membrane structure. Separation of grana from stroma thylakoids
      indicates that components responsible for transitions centered at approximately
      56, 73, 77, and 91 degrees C are predominantly or exclusively associated with
      grana thylakoids, whereas components responsible for transitions centered at
      approximately 63 and 81 degrees C are predominantly associated with stroma
      thylakoids. A broad transition centered at 66 degrees C is associated with grana
      thylakoids, whereas a sharp transition at the same temperature is due to a
      component associated with stroma thylakoids. Evidence obtained by washing
      treatments suggests the latter transition originates from the denaturation of the
      thylakoid ATPase (CF1). Analysis of the calorimetric enthalpy values indicates
      most components of the grana thylakoids denature irreversibly at high
      temperature, whereas components associated with the stroma thylakoids have a
      considerable degree of thermal reversibility.

PMID- 1386215
TI  - Sleep and psychiatric disorders. A meta-analysis.
AB  - We reviewed the literature on sleep in psychiatric disorders and evaluated the
      data by meta-analysis, a statistical method designed to combine data from
      different studies. A total of 177 studies with data from 7151 patients and
      controls were reviewed. Most psychiatric groups showed significantly reduced
      sleep efficiency and total sleep time, accounted for by decrements in non-rapid
      eye movement sleep. Rapid eye movement sleep time was relatively preserved in all
      groups, and percentage of rapid eye movement sleep was increased in affective
      disorders. Reduction in rapid eye movement sleep latency was seen in affective
      disorders but occurred in other categories as well. Although no single sleep
      variable appeared to have absolute specificity for any particular psychiatric
      disorder, patterns of sleep disturbances associated with categories of
      psychiatric illnesses were observed. Overall, findings for patients with
      affective disorders differed most frequently and significantly from those for
      normal controls.

PMID- 1386216
TI  - Lipid analysis of the major salivary glands in streptozotocin-diabetic rats and
      the effects of insulin treatment.
AB  - Two separate sets of experiments were performed on female Wistar rats made
      diabetic with streptozotocin: (1) a time-course study where groups of three
      animals were removed at weekly intervals, up to 4 weeks after induction of
      diabetes, with an age-matched group of control (normal) animals kept for 4 weeks;
      (2) six further animals were made diabetic and kept for 7 weeks; three of these
      were given insulin in the final week. At the required time the animals were
      anaesthetized and the salivary glands removed and preserved by fixation or
      freezing. The frozen tissues were later homogenized and the protein and lipid
      content analysed. Histologically, intracellular lipid droplets had accumulated in
      the majority of the diabetic salivary glands. In the time-course experiment, the
      visible amount of intracellular lipid reached a maximum after 2 weeks and then
      decreased, with a concomitant disappearance of interstitial lipid. The increased
      lipid content was not attributable to any one class. The fatty acid profiles of
      the glands showed an increase in the percentages of C18:0 (stearic acid) and
      C18:2w6 (linoleic acid) and a decrease in the percentages of C18:1w9 (oleic acid)
      and C20:4w6 (arachidonic acid). After 1 week of insulin treatment the lipid
      content and the fatty acid profiles returned to normal. Thus the effect of
      insulin on salivary gland lipid metabolism is rapid both in its occurrence and
      reversibility. The effects seen in the diabetic rats are considered to be due to
      a lack of insulin and not to the presence of streptozotocin.

PMID- 1386217
TI  - Inactivation of sarcoplasmic-reticulum Ca(2+)-ATPase in low-frequency-stimulated
      muscle results from a modification of the active site.
AB  - Molecular changes underlying the partial inactivation of the sarcoplasmic
      reticulum (SR) Ca(2+-) ATPase in low-frequency-stimulated fast-twitch muscle were
      investigated in the present study. The specific Ca(2+)-ATPase activity, as well
      as the ATP- and acetyl phosphate-driven Ca2+ uptakes by the SR, were reduced by
      approx. 30% in 4-day-stimulated muscle. Phosphoprotein formation of the enzyme in
      the presence of ATP or Pi was also decreased to the same extent. Measurements of
      ATP binding revealed a 30% decrease in binding to the enzyme. These changes were
      accompanied by similar decreases in the ligand-induced (ATP, ADP, Pi) intrinsic
      tryptophan fluorescence. A decreased binding of fluorescein isothiocyanate (FITC)
      corresponded to the lower ATP binding and phosphorylation of the enzyme.
      Moreover, Pi-induced changes in fluorescence of the FITC-labelled enzyme did not
      differ between SR from stimulated and contralateral muscles, indicating that
      Ca(2+)- ATPase molecules which did not bind FITC were responsible for the
      decreased Pi-dependent phosphorylation, and therefore represented the inactive
      form of the enzyme. No differences existed between the Ca(2+)-induced changes in
      the intrinsic fluorescence of SR from stimulated and contralateral muscles which
      fit their similar Ca(2+)-binding characteristics. Taking the proposed
      architecture of the Ca2(+)-ATPase into consideration, our results suggest that
      the inactivation relates to a circumscribed structural alteration of the enzyme
      in sections of the active site consisting of the nucleotide-binding and
      phosphorylation domains.

PMID- 1386219
TI  - Telecommunications for the disabled.
AB  - Scientific and technological advances should be used to give the disabled every
      possible opportunity for personal development. There is great scope for improving
      the lot of disabled people by providing access to modern telecommunications
      systems. In the Third World, such progress could be encouraged if donor agencies
      stipulated that a certain proportion of funding should serve this purpose.

PMID- 1386218
TI  - Protein kinase C enhances myosin light-chain kinase effects on force development
      and ATPase activity in rat single skinned cardiac cells.
AB  - Many neurohormones alter the force of cardiac contraction by variations in the
      intracellular Ca2+ concentration. alpha 1-Adrenergic and muscarinic stimulations,
      rather, modify the sensitivity of contractile proteins to Ca(2+)-calmodulin
      myosin light-chain kinase (MLCK) complex induces a large increase in Ca2+
      sensitivity (0.14 pCa unit) of these easily accessible myofilaments. This
      increase is further enhanced by up to 0.19 pCa unit when protein kinase C (PKC)
      is added together with MLCK. Similarly, the Ca2+ ATPase activity of skinned cells
      in suspension is increased in the presence of MLCK and further in the presence of
      both kinases. 32P-labelling and SDS/PAGE show that these changes are associated
      with light-chain 2 (LC2) phosphorylation together with phosphorylation of
      troponin I and troponin T when PKC is added. Although to a smaller extent than in
      smooth muscle, phosphorylation of cardiac myosin LC2 may be involved in the
      modulation of heart contractility.

PMID- 1386220
TI  - Effects of 5-HT-1A receptor agonists on ethanol preference in the rat.
AB  - Pharmacological manipulation of brain serotonin (5-HT) neurons has recently
      become recognized as an important approach in the treatment of ethanol (ET-OH)
      dependence. In the present study, we observed the effects of three agonists of 5
      HT-1A receptor subtype, 8-OHDPAT, buspirone, and NDO-008, on ET-OH preference in
      Wistar male rats. Animals received ET-OH intragastrically during the first week
      of the experiment, and then during 2 consecutive weeks, the only source of fluid
      (23 h/d) was 5% and 8% wt/vol ET-OH solution, respectively. Then the animals were
      presented with a free-choice between water and 8% ET-OH solution for a 1-week
      period. Based on the baseline recordings, two groups of rats were formed: a high
      preference group (ET-OH intake greater than 50% of total daily fluid intake) and
      a low preference group of rats (ET-OH intake less than 20%). During week 5 of the
      experiment, animals were treated with 5-HT receptor agonists (subcutaneous
      injections twice daily for 4 days). The treatment caused a significant reduction
      of ET-OH intake in the high preference group, but caused no change in the
      remaining groups. The effect of highly selective 5-HT-1A receptor agonist, 8
      OHDPAT, on ET-OH consumption in the high preference group was antagonized by
      cyanopindolol, a nonselective antagonist of 5-HT-1 receptor subtype. Our results
      support the hypothesis that activation of 5-HT-1A receptors reduces ET-OH
      preference.

PMID- 1386221
TI  - Atrial natriuretic peptide and the baroreflex control of circulation.
AB  - An emerging role for atrial natriuretic peptide (ANP) as a modulator of
      baroreflex function is suggested by a number of experimental observations. In
      several animal species and in humans, ANP appears to reset the baroreflex control
      of heart rate in a way that favors bradycardia and opposes cardioacceleration. In
      addition, ANP interferes with the reflexes originating from cardiopulmonary
      receptors in the control of vascular tone. The modulation of baroreflexes by ANP
      seems to be related, at least in part, to the interaction of the atrial peptide
      with the effects of angiotensin II. This influence of ANP on the baroreflex
      control of circulation may be important in short-term cardiovascular adaptations,
      and may have particular relevance to conditions characterized by volume overload
      and impaired baroreflex function, such as certain forms of hypertension and
      congestive heart failure.

PMID- 1386222
TI  - Comparison of atracurium-induced neuromuscular block in rectus abdominis and hand
      muscles of man.
AB  - We have compared neuromuscular block in the rectus abdominis and the hand muscles
      in 11 adult patients. Atracurium 0.5 mg kg-1 was administered by single bolus and
      anaesthesia maintained with isoflurane and nitrous oxide in oxygen. Train-of-four
      (TOF) stimulation was applied to the 10th intercostal space in the anterior
      axillary line and to the ulnar nerve at the wrist. Electromyographic (EMG)
      responses were recorded over the rectus abdominis and hypothenar muscles.
      Neuromuscular block had a significantly faster onset in the rectus abdominis
      (mean 1.6 (SEM 0.2) min) than in the hand (2.4 (0.3) min) (P less than 0.001).
      Recovery occurred more rapidly in the rectus abdominis: time to 25% TOF recovery
      was 39 (3) min at rectus abdominis and 51 (4) min at the hand (P less than
      0.001). Time to 75% TOF recovery was 56 (4) min at rectus abdominis and 72 (6)
      min at the hand (P less than 0.001).

PMID- 1386223
TI  - The role of enoximone in cardiac surgery.
AB  - After cardiopulmonary bypass (CPB), some patients may require circulatory
      support. This study examined the role of the phosphodiesterase-III inhibitor,
      enoximone, in cardiac surgery. Eighty patients selected by chance were allocated
      randomly to two groups: 40 patients received enoximone 1.0 mg kg-1 approximately
      10 min before weaning from CPB and 40 served as a control group. Additional
      pharmacological therapy (adrenaline, noradrenaline, nitroglycerin) was given,
      when necessary, by anaesthetists who were not involved in the study. In addition
      to standard monitoring, skin capillary blood flow was assessed using a laser
      Doppler technique before, during and after CPB until 2 h after the end of the
      operation. In the period after bypass, cardiac index was always significantly
      greater in the enoximone than in the control group. Systemic and pulmonary
      vascular resistance were less in the enoximone-treated patients, indicating a
      reduction in right and left ventricular wall stress. Oxygen consumption in the
      enoximone patients was significantly greater after CPB, whereas intrapulmonary
      shunting was comparable in the two groups. In comparison with baseline values,
      skin capillary blood flow in the enoximone patients was always greater than that
      in the control group. In comparison with the control patients, significantly
      fewer enoximone patients needed adrenaline, and in a smaller dose, even 2 h after
      operation, whereas more enoximone patients required noradrenaline therapy for a
      short period. We conclude that the use of enoximone before weaning from CPB
      improved overall cardiac function, reduced the need of catecholaminergic
      inotropic support, and provided increased organ perfusion up to 2 h after
      operation.

PMID- 1386225
TI  - [Left side approach in laparoscopic cholecystectomy: first-year experience].
AB  - Laparoscopic cholecystectomy can be performed following two main approaches: the
      french technique, used by the majority of surgeons, and the anglo-saxon
      technique. The Authors describe the basic concept of the "left side" approach
      according to the Anglo-american method, underlining some of the advantages. Their
      one-year results (November 1990-November 1991) confirm the data already available
      in the Literature.

PMID- 1386224
TI  - Comparison of extradural administration of sufentanil, morphine and sufentanil
      morphine combination after caesarean section.
AB  - We have studied postoperative analgesia and unwanted side effects of a single
      dose of a mixture of morphine and sufentanil administered extradurally with the
      effects produced by extradural injection of each opioid alone in 64 patients
      after Caesarean delivery. The patients were allocated randomly to receive
      morphine 4 mg (n = 21), sufentanil 50 micrograms (n = 22) or morphine 2 mg with
      sufentanil 25 micrograms (n = 21) via an extradural catheter in a double-blind
      design. Intensity of pain was measured using a linear visual analogue scale.
      Compared with the effect produced by morphine alone, the morphine-sufentanil
      combination produced more rapid onset of pain relief (19 (SD 5) min vs 79 (23)
      min for a 75% reduction of pain; P less than 0.01), whereas the duration and
      quality of analgesia assessed during 12 h was similar for these two groups. In
      contrast, patients receiving sufentanil alone required significantly more
      supplementary analgesia 4 h after administration than with morphine alone or
      morphine combined with sufentanil. There were no significant changes in
      cardiorespiratory variables in any group. Side effects consisted mainly of
      pruritus and nausea and did not differ between groups, with the exception of
      early and transient dizziness which was observed only in patients given
      sufentanil either alone or in combination with morphine. We conclude that a
      single extradural injection of morphine and sufentanil combines the short onset
      time produced by sufentanil and the long duration of analgesia attributable to
      morphine, thus providing excellent and prolonged analgesia after Caesarean
      delivery.

PMID- 1386226
TI  - [Laparoscopic cholecystectomy: analysis of first 203 cases].
AB  - Laparoscopic cholecystectomy is a valid alternative to open cholecystectomy. The
      Authors present their experience in the management of 208 consecutive patients.
      The low incidence of complications, the short hospital stay as well as earlier
      return to work, and lower medical expenses are the advantages of laparoscopic
      surgery. The latter is, therefore, more suitable for the treatment of benign
      gallbladder diseases.

PMID- 1386228
TI  - [Laparoscopic cholecystectomy in acute cholecystitis].
AB  - In a 18 month period 19 patients (4.7%) out of 400 affected by acute
      cholecystitis underwent laparoscopic cholecystectomy. In 18 cases the diagnosis
      was preoperative on clinical signs or ultrasound scan basis. Intraoperative and
      histologic confirm was obtained in all cases. Mean age was 44.9, 11 were males
      and 8 females. The procedure resulted longer and more difficult compared to the
      global series of the same period: 90 min. versus 56 min. respectively, with a
      difficulty score higher than 4 in 89% of cases versus 40% of the global series.
      Furthermore, in 56% of cases versus 23.3% of the global series an intraoperative
      contamination from gallbladder content was recorded. Nevertheless, only 1 (5%)
      minor complication was observed, in the form of omphalitis, which recovered in 2
      days. Therefore, discharge was possible in average within 4 days, excluding the
      first two cases operated, respectively discharged in 5th and 7th p.o. day as a
      precautionary measure. Early coelioscopic cholecystectomy is safe and effective,
      if carried out by well trained surgeons, even in acute cholecystitis.

PMID- 1386227
TI  - [Anatomo-surgical considerations in laparoscopic cholecystectomy].
AB  - The Authors emphasize the importance of a perfect anatomo-surgical knowledge for
      laparoscopic cholecystectomy. Therefore, the anatomic structures of the region
      are taken into account from a "laparoscopic" point of view, with great care to
      accessory bile duct, hepatic artery, and cystic artery. Knowledge and confidence
      with the anatomy of the region are essential to identify abnormal structures and
      subsequently switch from a laparoscopic to a laparotomic approach.

PMID- 1386230
TI  - [Laparoscopic cholecystectomy: considerations on the technique].
AB  - The Authors analyze the single steps of laparoscopic cholecystectomy and describe
      the technique usually preferred. On the basis of the experience acquired,
      advantages and disadvantages of each manoeuver and instrument available are
      pointed out.

PMID- 1386229
TI  - [Laparoscopic cholecystectomy using argon bistoury].
AB  - A total of 92 patients were submitted to laparoscopic cholecystectomy during the
      period Autumn 1990-Spring 1991. The dissection of the gallbladder from the
      hepatic bed was performed in 40 patients using the Argon beam coagulator, in 25
      using the monopolar electrocoagulator and in 27 using the Holmio laser beam. In
      average, with the Argon beam coagulator time procedure was respectively 2.7 and
      5.4 minutes shorter than monopolar electrocoagulator and Holmio laser. Only one
      complication (pneumomediastinum) was correlated with the use of the Argon beam
      coagulator.

PMID- 1386231
TI  - [Mini-invasive surgical treatment of gallstones and common bile duct calculi].
AB  - Between June 1st 1990 and December 31st 1991, 449 patients with cholelithiasis
      were operated on. All patients with isolated cholecystolithiasis (400) were
      offered video-laparoscopic (VLC) treatment. Forty-nine patients had both
      cholecystolithiasis and choledocholithiasis. They all underwent further
      evaluation by ERCP, on the basis of which 30 patients were selected for
      sequential endoscopic and laparoscopic treatment with endoscopic
      papillosphincterotomy (EPST) followed by VLC. Three patients were selected for
      VLC and ideal laparoscopic choledocholithotomy. No complications were observed.
      At present, sequential ERCP-PST and VLC treatment seems to be the ideal approach
      to combined cholecystic and choledochal lithiasis in terms of safety, efficacy
      and tolerability. The increasing surgical skill in the field of minimally
      invasive surgery and the availability of sophisticated laparoscopic
      instrumentation allow to consider VLC and laparoscopic choledocholithotomy a
      valid alternative in terms of reduced surgical trauma and patient discomfort.

PMID- 1386232
TI  - [Aseptic resection of the intraluminal colon in laparoscopy].
AB  - Laparoscopic surgery is an "old" technique extending to new applications
      including colon surgery. Basically, even though surgical technique and
      indications do not differ from traditional surgery, it has the advantage to
      eliminate most of the complications associated with an abdominal incision. In
      order to improve also the outcome of intestinal anastomoses, an aseptic technique
      by intestinal intussusception previously described (3) has been modified and
      carried out laparoscopically in 3 pigs and 3 dogs successfully. The animals were
      sacrificed after 2 months. Anastomoses were evaluated endoscopically by barium
      enema and by gross and microscopic examination. Results indicated no mortality or
      complications except for a small area of mucosal peri-anastomotic necrosis in one
      dog, which spontaneously healed. Therefore, it seems that the aseptic resection
      of the colon is possible with laparoscopy obtaining at the same time a decreased
      morbidity related to the abdominal incision and colonic anastomosis.

PMID- 1386234
TI  - [Laparoscopic appendectomy].

PMID- 1386233
TI  - Minimally invasive surgery.

PMID- 1386235
TI  - [Video laparoscopic cholecystectomy].

PMID- 1386236
TI  - From ASCO: recommended criteria for the performance of bone marrow
      transplantation.

PMID- 1386237
TI  - Tobacco taxes in industrialized countries.

PMID- 1386238
TI  - Recommendations regarding estrogen replacement therapy after treatment of
      endometrial cancer.
AB  - A history of endometrial cancer has long been considered a contraindication to
      estrogen replacement therapy. Yet women with such a history, like other women
      when postmenopausal, often suffer vasomotor symptoms that could easily be
      relieved with estrogen. In fact there is no good evidence that estrogen
      significantly increases the risk of recurrence after treatment for endometrial
      cancer. Some studies now suggest that estrogen plus a progestin may actually
      decrease the risk of cancer recurrence in these patients. The benefits of
      estrogen in preventing osteoporosis and cardiovascular disease in postmenopausal
      women is substantial.

PMID- 1386239
TI  - Tamoxifen prophylaxis in breast cancer.
AB  - An increasing body of data suggests that tamoxifen can suppress development of
      preclinical breast cancer. Newer data in postmenopausal women also demonstrate
      major biologic effects of tamoxifen on risk factors for cardiovascular disease
      and osteoporosis. Taken together, this information supports the hypotheses that
      use of tamoxifen will provide overall health benefits and lower the incidence of
      breast cancer in selected women, particularly postmenopausal women, who are
      willing to take a daily hormone pill indefinitely and who do not develop
      significant symptomatic side effects. Clinical trials addressing these hypotheses
      are beginning in the United States, Great Britain, and Italy, but the design and
      completion of such trials present significant challenges. Until clear data are
      available from the clinical trials just being launched, tamoxifen should not be
      given to healthy women who do not have breast cancer.

PMID- 1386240
TI  - Breast cancer prevention trial will recruit 16,000 women.

PMID- 1386241
TI  - Lung cancer clinic streamlines consultation.

PMID- 1386242
TI  - Endoscopic ultrasonography: an effective new tool for diagnosing gastrointestinal
      tumors.
AB  - Endoscopic ultrasonography is a new technique used to evaluate the
      gastrointestinal tract and contiguous organs. High resolution endoscopic
      ultrasound dramatically improves tumor characterization, and enables more precise
      TNM staging. The earlier diagnosis achieved with this technique combined with
      more precise staging, permits the most effective timing and selection of
      chemotherapy, radiation therapy, and surgery. This new technology will almost
      certainly have great impact on the clinical outcome of patients with
      gastrointestinal tumors.

PMID- 1386243
TI  - Children with AIDS benefit from two-drug regimen.

PMID- 1386244
TI  - TCA chemical peel found effective in treating premalignant skin lesions.

PMID- 1386245
TI  - Comparison of the anti-emetic efficacy of different doses of ondansetron, given
      as either a continuous infusion or a single intravenous dose, in acute cisplatin
      induced emesis. A multicentre, double-blind, randomised, parallel group study.
      Ondansetron Study Group.
AB  - A total of 535 chemotherapy naive, hospitalised patients (263 male/272 female)
      scheduled to receive cisplatin (50-120 mg m-2)-containing regimens participated
      in a randomised, double-blind, parallel group study to evaluate the efficacy and
      safety of three intravenous dose schedules of ondansetron in the prophylaxis of
      acute nausea and emesis. One hundred and eighty two patients received a loading
      dose of 8 mg of ondansetron followed by a 24 h infusion of 1 mg h-1 (group 1);
      180 and 173 patients received single doses of 32 mg (group II) and 8 mg (group
      III) respectively, followed by a 24 h placebo infusion. Complete and major
      control (less than or equal to 2 emetic episodes) of acute emesis was achieved in
      74% of patients in group I, 78% in group II and 74% in group III. Seventy seven
      per cent of the patients in group I, and 75% of patients in groups II and III
      respectively experienced no or mild nausea during the 24 h observation period. A
      retrospective stratification of the efficacy data on the basis of patient gender
      showed the response rate in females to be significant lower (43% vs 67%; less
      than 0.001). Ondanestron was well tolerated; mild headache was the most commonly
      reported adverse event (11% of patients) with a similar incidence in the three
      groups of patients. In conclusion, a single intravenous dose of 8 mg of
      ondansetron given prior to chemotherapy is as effective as a 32 mg daily dose
      given as either a single dose of a continuous infusion in the prophylaxis of
      acute cisplatin-induced emesis.

PMID- 1386246
TI  - A prospective study into the value of patch and intradermal tests in identifying
      topical corticosteroid allergy.
AB  - We have prospectively performed patch and intradermal tests on 105 consecutive
      patients, attending for patch testing, to determine the optimum method of
      screening for corticosteroid hypersensitivity. Patch tests with Pivalone and a
      corticosteroid series (all 1% in ethanol) detected all the patients with steroid
      sensitivity. However, intradermal tests were essential to exclude false positive
      reactions and detect all relevant steroid allergies in any individual patient.

PMID- 1386247
TI  - Purpura fulminans due to protein S deficiency following chickenpox.

PMID- 1386248
TI  - "Clawbacks".

PMID- 1386249
TI  - Dehydroepiandrosterone sulfate and other possible influencing factors that
      modulate sex hormone-binding globulin levels in the hirsute patient.
AB  - This study was designed to investigate the most important factors affecting serum
      concentrations of sex hormone-binding globulin (SHBG) in women with hirsutism. We
      compared endocrine profiles based on biochemical measurements of LH, FSH,
      oestradiol, testosterone (T), prolactin, 17-hydroxy-progesterone,
      dehydroepiandrosterone sulphate (DHEAS), SHBG, cortisol and insulin in the
      follicular phase in 32 healthy women and 52 patients. The study group was
      subdivided according to SHBG levels into Group A (low level) and Group B (high
      level). Significant differences between Groups A and B were found in DHEAS and T
      levels, but not in body mass index or insulinaemia. There was a relationship
      between DHEAS and SHBG levels (r = 0.51) and between T and SHBG (r = 0.31). We
      conclude that DHEAS may be a significant modulator of SHBG in the female hirsute
      patient, an observation seldom mentioned in previous reports.

PMID- 1386250
TI  - A theoretical study concerning the mode of interaction of the histamine H2
      agonist dimaprit.
AB  - A theoretical study was performed to elucidate the mode of interaction of the
      histamine H2-agonist dimaprit with the histamine H2-receptor. For this purpose
      receptor mapping techniques, including ab initio energy calculations, geometry
      optimizations and molecular electrostatic potential calculations (MEPs), have
      been used. The characteristics of dimaprit were compared to those of histamine
      for which the points of interaction with the H2-receptor are known, as well as
      its bioactive conformation. In this comparative study two possible models for the
      interaction of dimaprit with the H2-receptor were considered. In one model the
      two nitrogen atoms of the isothiourea moiety of dimaprit play an essential role
      in the recognition of the ligand by the receptor and have the same function as
      the nitrogen atoms of the imidazole ring of histamine; in the second model this
      role is fulfilled by a sulphur and a nitrogen atom of the same isothiourea
      moiety. The comparison to histamine was based on geometrical resemblance as well
      as on similarity in MEPs. Also the conformational energy of dimaprit in the two
      interaction models was considered. Results of the investigations reveal that the
      isothiourea moiety of dimaprit most probably interacts with the histamine H2
      receptor through the sulphur and nitrogen atom, the first atom acting as a proton
      acceptor and the second one as a proton donor. Subsequently, three analogues of
      dimaprit, namely SK&F 91487, SK&F 91488 and SK&F 92054, were studied. It was
      possible to explain their pharmacological behavior within the proposed
      model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386251
TI  - Activation of CD8+ murine T cells from tumor-draining lymph nodes by phorbol
      dibutyrate plus calcium ionophore.
AB  - When lymphocytes from the lymph nodes draining the site of a progressively
      growing MCA-105 sarcoma are stimulated in vitro with autologous tumor and low
      dose interleukin-2 (IL-2), they will grow and develop the ability to lyse
      autologous tumor cells in vitro; these lymphocytes can also eradicate tumor
      metastases in vivo. Phorbol esters and calcium ionophores activate signal
      transduction pathways in T cells and mimic the events triggered by antigen
      binding. We therefore sought to determine whether large numbers of MCA-105 tumor
      specific, therapeutically active T cells could be obtained from MCA-105 draining
      lymph nodes (DLNs) following a brief exposure to phorbol dibutyrate (PDBu) and
      ionomycin (Io). DLN cells primarily stimulated with autologous tumor, followed by
      a secondary stimulation with PDBu-Io and cultured in 20 U/ml IL-2, demonstrated
      marked expansion of cell numbers during 3 weeks in culture, had moderate
      cytolytic activity [37% at effector:target ratio (E:T) = 80:1], and were all CD8+
      T cells. In contrast, DLN cells stimulated primarily with PDBu-Io and cultured in
      20 U/ml IL-2 demonstrated at least 8-10-fold greater growth than antigen
      stimulated DLN cells during 3 weeks, were moderately cytolytic (31% at E:T =
      80:1), and were a mixed population of CD8+ and CD4+ T lymphocytes. DLN cells that
      were expanded by either protocol, like cells stimulated repeatedly in vitro with
      tumor cells, could eliminate MCA-105 pulmonary metastases when given with IL-2 in
      an adoptive immunotherapy model. DLN cells stimulated primarily with PDBu-Io
      completely eradicated MCA-105 metastases but had no in vivo antitumor activity
      against the syngeneic B16 melanoma or MCA-203 sarcoma.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1386252
TI  - Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis
      of 27 trials.
AB  - To calculate the effect of changes in carbohydrate and fatty acid intake on serum
      lipid and lipoprotein levels, we reviewed 27 controlled trials published between
      1970 and 1991 that met specific inclusion criteria. These studies yielded 65 data
      points, which were analyzed by multiple regression analysis using isocaloric
      exchanges of saturated (sat), monounsaturated (mono), and polyunsaturated (poly)
      fatty acids versus carbohydrates (carb) as the independent variables. For high
      density lipoprotein (HDL) we found the following equation: delta HDL cholesterol
      (mmol/l) = 0.012 x (carb----sat) + 0.009 x (carb----mono) + 0.007 x (carb----
      poly) or, in milligrams per deciliter, 0.47 x (carb----sat) + 0.34 x (carb---
      mono) + 0.28 x (carb----poly). Expressions in parentheses denote the percentage
      of daily energy intake from carbohydrates that is replaced by saturated, cis
      monounsaturated, or polyunsaturated fatty acids. All fatty acids elevated HDL
      cholesterol when substituted for carbohydrates, but the effect diminished with
      increasing unsaturation of the fatty acids. For low density lipoprotein (LDL) the
      equation was delta LDL cholesterol (mmol/l) = 0.033 x (carb----sat) - 0.006 x
      (carb----mono) - 0.014 x (carb----poly) or, in milligrams per deciliter, 1.28 x
      (carb----sat) - 0.24 x (carb----mono) - 0.55 x (carb---- poly). The coefficient
      for polyunsaturates was significantly different from zero, but that for
      monounsaturates was not. For triglycerides the equation was delta triglycerides
      (mmol/l) = -0.025 x (carb----sat) - 0.022 x (carb----mono) - 0.028 x (carb----
      poly) or, in milligrams per deciliter, -2.22 x (carb----sat) - 1.99 x (carb---
      mono) - 2.47 x (carb----poly).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386253
TI  - Multiple amino acid substitutions suggest a structural basis for the separation
      of biological activity and receptor binding in a mutant interleukin-1 beta
      protein.
AB  - Receptor binding and biological activity properties of human interleukin-1 beta
      can be dissociated by mutating a single amino acid, arginine 127, to glycine (IL
      1 beta R----G) [Gehrke et al. (1990) J. Biol. Chem. 265, 5922-5925]. The
      mechanism underlying the reduced biological activity has been examined by
      replacing arginine 127 with several other amino acids, followed by determination
      of biological activity using a T-helper cell proliferation assay. Mutant IL-1
      beta proteins containing lysine, glutamic acid, tryptophan, or alanine in place
      of arginine 127 maintain biological activity. These data strongly suggest that IL
      1 beta biological activity is not directly dependent upon the specific properties
      of charge, hydrophobicity/hydrophilicity, or side-chain group presented by the
      residue at position 127. Molecular modeling analyses indicate that the structural
      integrity of the antiparallel beta-strand 1/12 pair is disturbed in the glycine
      127 mutant protein. Collapse of beta-strand 1 into a hydrated space between
      strands 1, 2, and 4 could structurally alter a cleft in IL-1 beta that contains a
      cluster of highly conserved amino acids, including a key aspartic acid residue
      [Ju et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 2658-2662]. Mutagenesis data
      and the differential activities of the IL-1 beta R----G and IL-1 receptor
      antagonist proteins in stimulating early and late gene expression [Conca et al.
      (1991) J. Biol. Chem. 266, 16265-16268] suggest that multiple receptor-ligand
      contacts, exclusive of those required for receptor binding, are required for the
      stimulation of full IL-1 biological activity.

PMID- 1386254
TI  - Minimum length of a sequence-specific DNA binding peptide.
AB  - NMR experiments show that a stable complex can be formed between a 14-base-pair
      oligonucleotide and a disulfide-bonded dimer of a peptide containing 27 residues
      of the basic region of the yeast transcriptional activator GCN4; the complex is
      in slow exchange on the NMR time scale. In contrast, a nonspecific complex is in
      fast exchange on the NMR time scale. DNase I footprinting experiments show that
      dimers of peptides containing as few as 20 residues of GCN4 bind DNA with
      sequence specificity similar to that of the intact protein. Circular dichroism
      experiments suggest that specific binding involves only 15 residues,
      corresponding to residues 231-245 of GCN4, in an alpha-helical conformation.
      These results limit substantially the region of GCN4 involved in sequence
      specific DNA contacts and provide a uniquely simple model for studying protein
      DNA interactions in detail.

PMID- 1386255
TI  - Cytoplasmic location of amino acids 359-440 of the Neurospora crassa plasma
      membrane H(+)-ATPase.
AB  - The topographic location of the region comprising amino acids 359-440 of the
      Neurospora crassa plasma membrane H(+)-ATPase has been elucidated using
      reconstituted proteoliposomes and protein chemical techniques. Proteoliposomes
      containing H(+)-ATPase molecules oriented predominantly with their cytoplasmic
      surface facing outward were cleaved with trypsin and the resulting digest was
      subjected to centrifugation on a glycerol step gradient to separate the released
      and liposome-bound peptides. The released peptides were recovered in the upper
      regions of the step gradient, whereas the liposome-bound peptides were recovered
      near the 40% glycerol interface. The released peptides present in the upper
      fractions were reduced, 14C-carboxy-methylated, and then separated by high
      performance liquid chromatography. Two radioactive cysteine-containing peptides
      with retention times of about 162 and 182 min were identified as H(+)-ATPase
      peptides comprising residues Leu363-Lys379 and Leu388-Arg414, respectively, by
      comparison to standards prepared from the purified ATPase. This information thus
      establishes a cytoplasmic location for residues 359-418 in the H(+)-ATPase
      polypeptide chain. It also infers a cytoplasmic location for residues 419-440,
      since this stretch of amino acids is too short to cross the membrane and return
      between regions known to be cytoplasmically located. These results and the
      results of other recent experiments establish the topographical location of
      nearly all of the 919 residues in the H(+)-ATPase molecule.

PMID- 1386256
TI  - Purification of a phosphatidylinositol/phosphatidylcholine transfer protein from
      Neurospora crassa.
AB  - This paper reports, for the first time, the purification of a phospholipid
      transfer protein (PLTP) from a fungus, Neurospora crassa. The protein was
      purified from the post-microsomal supernatant of N. crassa by successive
      chromatography on DEAE-cellulose, Sephadex-G75 and PBE 94 (pH 4-7). The purified
      protein (M(r) 38,000) was found to transfer phosphatidylinositol preferentially
      over phosphatidylcholine, like the PLTP from the yeast, Saccharomyces cerevisiae.
      PC transfer was completely inhibited by inactivation of free amino groups or
      tryptophan residues. Surprisingly, the protein did not cross-react with
      antibodies against the bovine brain PITP. The cellular content of the protein was
      maximal during the logarithmic phase of growth. However, no direct correlation
      between the content of the protein and PC transfer activity could be
      demonstrated.

PMID- 1386258
TI  - The expression of thromboxane A2 synthase and thromboxane A2 receptor gene in
      human uterus.
AB  - The expression of thromboxane (TX) A2 synthase and thromboxane A2 receptor gene
      in human uterus was investigated by immunoblotting, immunocytochemistry, Northern
      blot, in situ hybridization, and autoradiographic analyses. Human uterus contains
      a single immunoreactive protein of 55 kDa that corresponds to the molecular size
      of human TXA2 synthase. Human uterus also contains a single 2.8-kb TXA2 receptor
      mRNA transcript and a receptor protein that can bind TXA2 antagonist, 125I-PTA
      OH. The immunoreactive TXA2 synthase, TXA2 receptor mRNA, and protein are present
      in endometrial glands, stromal cells, myometrial smooth muscle, and uterine blood
      vessels. The TXA2 synthase and TXA2 receptors in different uterine cells varied
      within as well as between various reproductive states. There were differences in
      the binding site numbers even between elongated and circular myometrial smooth
      muscle in all reproductive states except postmenopause. In summary, the data
      presented demonstrate for the first time that different human endometrial and
      myometrial cells and uterine blood vessels express TXA2 synthase as well as TXA2
      receptor gene. The expression, as well as changes during various reproductive
      states, suggests that TXA2 could be an autocrine/paracrine regulator of human
      myometrial contractions, endometrial secretory functions, and intrauterine blood
      flow and could play a role in the initiation and/or progression of labor in
      women.

PMID- 1386257
TI  - Genetic animal models of depression and ethanol preference provide support for
      cholinergic and serotonergic involvement in depression and alcoholism.
AB  - The present article summarizes some comparative studies of the Fawn-Hooded (FH)
      rat, a potential animal model of ethanol preference, and the Flinders Sensitive
      Line (FSL) rat, a potential animal model of depression. Both FH and FSL rats
      exhibit high degrees of immobility in the forced swim test and have difficulty
      learning a two-way active avoidance task. However, there were no differences
      between the FH and FSL rats in the elevated plus maze. Studies of ethanol
      preference indicated high rates of ethanol intake (greater than 4 g/kg) and
      preference (greater than 50%) in the FH rats, but low rates of ethanol intake
      (less than 1.1 g/kg) and preference (less than 20%) in FSL rats. It is concluded
      that the FSL rats exhibit behaviors consistent with their being an animal model
      of depression, whereas the FH rats exhibit features consistent with their being
      an animal model of both depression and alcoholism. Psychopharmacological
      challenges indicated that both FSL and FH rats were more sensitive to the
      hypothermic effects of oxotremorine, a muscarinic agonist. However, FSL rats were
      also more sensitive to serotonergic agonists, and some of the present results and
      other investigators have reported serotonergic subsensitivity in the FH rats.
      Thus, FSL rats exhibit both cholinergic and serotonergic supersensitivity,
      whereas FH rats exhibit cholinergic supersensitivity but normal or reduced
      serotonergic sensitivity. Progeny from a genetic cross between FH and FSL rats
      exhibit cholinergic supersensitivity and have high ethanol preference scores.
      These data are consistent with genetic models suggesting that ethanol preference
      may be influenced by dominant genes, whereas cholinergic sensitivity may be
      influenced by recessive genes.

PMID- 1386259
TI  - [Renal stent implantation. The current indications, 2-year results and the
      possibilities for percutaneous stent recovery].
AB  - Use of the Strecker flexible balloon-expandable tantalum stent for treatment of
      renal artery stenosis after failed angioplasty or transaortic
      thrombendarterectomy was evaluated in 18 patients (17 hypertensive, 1
      normotensive). Right (n = 10) and left (n = 6) renal arteries were involved; in 2
      patients renal artery stenosis had developed after kidney transplantation.
      Indications for stent placement were inadequate immediate postangioplasty
      response (n = 16), and obstructing intimal flaps following transaortic
      endarterectomy (n = 2). Stent placement was technically successful (less than 20%
      residual stenosis) and patency was preserved in 14 patients. Mid-term results
      (mean, 12-13 months) of 11 patients showed restenoses (greater than 50%) in 2
      patients, and improvement of hypertension in 8 patients. The Strecker stent may
      be helpful in treating residual stenosis after failed revascularization
      procedures of the renal arteries, although long-term efficacy of stent placement
      will not be known until trials with more subjects and longer follow-up periods
      are completed.

PMID- 1386260
TI  - Plasma crosslinked fibrin polymers: quantitation based on tissue plasminogen
      activator conversion to D-dimer and measurement in normal and patients with acute
      thrombotic disorders.
AB  - Plasma crosslinked fibrin polymers (XLFP) are formed as a result of in vivo
      hemostatic activation and are elevated in thrombotic disease. We have
      investigated the plasmic degradation of plasma XLFP in vitro to provide
      information regarding the pattern of crosslinking and the composition of
      degradation products. Plasma XLFP were identified by sodium dodecyl sulfate (SDS)
      agarose electrophoresis and Western blotting and quantitated by gel scanning. D
      dimer was measured by enzyme-linked immunosorbent assay and the results were
      verified by SDS-polyacrylamide gel electrophoresis and Western blotting of the
      digests. Complete degradation of XLFP occurred only after supplementation of
      plasma with plasminogen (5 U/mL) and incubation with recombinant tissue
      plasminogen activator (rt-PA), indicating that the normal plasma plasminogen
      concentration limits plasmic degradation in vitro. Gel electrophoresis showed
      that the principal terminal degradation products of XLDP were fragments D, DD,
      and E, indicating that crosslinking occurred primarily through gamma chain
      dimers. After adding a low concentration of thrombin to plasma in vitro, XLFP
      increased progressively before clotting, and the concentration correlated with
      the increase in the D-dimer concentration after degradation (r = .98). Plasma
      XLFP and D-dimer concentrations in plasmic digests were significantly elevated in
      patients with stroke (150 +/- 83 micrograms/mL and 88 +/- 32 micrograms/mL),
      myocardial infarction (217 +/- 110 micrograms/mL and 84 +/- 30 micrograms/mL),
      and venous thrombosis (187 +/- 80 micrograms/mL and 86 +/- 19 micrograms/mL)
      compared with normals (28 +/- 12 micrograms/mL and 25 +/- 7 micrograms/mL). There
      was a strong correlation between the plasma concentration of XLFP and the D-dimer
      immunoreactivity of plasma after plasmic degradation (r = .87). The results
      indicate that XLFP in plasma are crosslinked primarily through gamma chains and
      degrade to fragment DD with plasminogen activation. Also, the immunoreactivity of
      in vitro plasmic digests of plasma reflects the concentration of XLFP and may
      provide a useful indirect measure of in vivo hemostatic activation in patients
      with thrombotic disease.

PMID- 1386261
TI  - Correlation between interferon (IFN) alpha resistance and deletion of the IFN
      alpha/beta genes in acute leukemia cell lines suggests selection against the IFN
      system.
AB  - Homozygous and hemizygous deletions of the interferon A (IFNA) and IFNB genes
      have been frequently observed in acute leukemia cell lines, primary acute
      leukemia cases, and gliomas. Because IFNs have an antiproliferative effect,
      selection against the IFN alpha/beta system could play a role or accompany the
      development of the malignant phenotype. Although the deletion of the IFNA/B genes
      could interrupt an autocrine loop that controls cell proliferation, cells would
      still respond to exogenous IFN alpha/beta and, thus, lesions at the receptor or
      signal transduction level should also be present to render cells resistant to
      exogenous IFN alpha/beta. To test if selection against the IFN system was
      operating in acute leukemias, the sensitivity to the antiproliferative effect of
      IFN alpha 2 was studied in acute leukemia cell lines with and without alterations
      of the IFNA/B genes. We found that 10 of 11 acute leukemia cell lines with
      alterations of the IFNA/B genes were resistant to the antiproliferative effect of
      IFN alpha 2, whereas only two of eight cell lines with normal IFNA/B genes were
      IFN-resistant. We then examined the possibility that an alteration of the
      receptor expression could account for the lack of response to IFN alpha 2. No
      significant alteration in the expression or structure of the IFN alpha receptor
      was observed. We also studied the downmodulation of the alpha subunit of the IFN
      alpha receptor upon IFN alpha 2 binding. One cell line with deletion of the
      IFNA/B genes showed impaired downmodulation of the IFN alpha receptor. The data
      presented here suggest that selection against the IFN alpha/beta system could
      play a role or accompany the development of the malignant phenotype.

PMID- 1386262
TI  - A prospective study of skeletal changes during short-term acitretin therapy.
AB  - We prospectively analyzed skeletal changes of 16 patients who were treated with
      acitretin for various disorders of keratinization at doses of 10-50 mg/day
      (overall mean 0.4 mg/kg/day) for 7-12 months (mean 11.4 months). Skeletal changes
      from pretherapy findings were observed in 5 patients. In 4 of 5 patients they
      appeared to be linked to a preexisting degenerative pathology and could not be
      attributed to acitretin therapy. However, in 1 patient a spinal osseous side
      effect could not be excluded. No retinoid-induced extraspinal tendon or ligament
      calcifications were observed.

PMID- 1386263
TI  - Ultrastructural changes in onychomycosis during the treatment with
      bifonazole/urea ointment.
AB  - In the present study, we investigated the effects of bifonazole/urea ointment, a
      novel topical drug for the treatment of onychomycosis, on the ultrastructure of
      normal and fungus-infected human toenails by scanning electron microscopy. Nails
      were treated with the drug ex vivo and compared to untreated controls. During
      treatment, the corneocyte layers disintegrated, and the structure markedly
      loosened. After 5 days of treatment, the morphology of fungal cells, found at the
      undersurface of infected nails, was changed due to the antifungal drug action.
      The present data demonstrate that by the use of this drug, the agent effectively
      penetrates the nail plate and affects the fungal cells.

PMID- 1386264
TI  - Inhibition of neutrophil chemotactic factor production in comedonal bacteria by
      subminimal inhibitory concentrations of erythromycin.
AB  - The effect of 1/10 minimal inhibitory concentrations (sub-MIC) of erythromycin
      (EM) on human neutrophil chemotactic factor production in comedonal bacteria,
      Propionibacterium acnes strains, Propionibacterium granulosum strains and
      coagulase-negative staphylococcus (CNS) strains was assayed using the Boyden
      chamber method. Sub-MIC of EM significantly suppressed neutrophil chemotactic
      factor production in all strains of P. acnes, P. granulosum and CNS. Our results
      suggest that sub-MIC of EM may have an anti-inflammatory action by reducing the
      inflammatory capacity of comedonal bacteria in inflammatory acne.

PMID- 1386265
TI  - Murine erythrocyte ankyrin cDNA: highly conserved regions of the regulatory
      domain.
AB  - Ankyrin is an essential link between cytoskeletal proteins, such as spectrin, and
      membrane bound proteins, such as protein 3, the erythrocyte anion exchanger.
      Although the amino acid structure of human ankyrin is known, the functional
      regions have been only partially defined. Sequence comparisons between mouse and
      human ankyrin offer one mechanism of identifying highly conserved regions that
      probably have functional significance. We report the isolation and sequencing of
      a series of overlapping murine erythroid ankyrin (Ank-1) cDNAs from spleen and
      reticulocyte libraries (total span 6238 bp) and identify potentially important
      regions of murine-human reticulocyte ankyrin homology. Comparison of the
      predicted peptide sequences of mouse and human erythroid ankyrins shows that
      these ankyrins are highly conserved in both the N-terminal, protein 3 binding
      domain (96% amino acid identity) and in the central spectrin-binding domain (97%
      identity), but differ in the C-terminal regulatory domain (79% identity).
      However, the C-terminal regulatory domain contains two regions of peptide
      sequence that are perfectly conserved. We postulate these regions are important
      in the regulatory functions of this domain.

PMID- 1386267
TI  - The CREB family of transcription activators.
AB  - A diverse family of transcription factors bind to the cAMP-response elements
      found in a variety of mammalian and viral gene promoters. One of the members of
      this family, CREB, is being intensively studied so as to elucidate the mechanisms
      by which second messenger signal transduction pathways act to positively and
      negatively regulate transcription.

PMID- 1386266
TI  - The circadian rhythm of atrial natriuretic peptide, vasoactive intestinal
      peptide, beta-endorphin and cortisol in healthy young and elderly subjects.
AB  - Atrial natriuretic peptide, vasoactive intestinal peptide, beta-endorphin and
      cortisol are humoral variables characterized by a 24-h periodicity. We evaluated
      the circadian rhythm of these peptides and hormones in healthy subjects who were
      young (between 20-25 years) or elderly (between 65-75 years). All were on
      controlled diets. Blood samples were collected six times during a 24-h period (at
      06.00, 08.00, 12.00, 18.00, 20.00 and 24.00 h) beginning 8-h after start of
      recumbency. The time-related data were analysed by the Cosinor method in order to
      validate the circadian rhythm and to quantify rhythmometric parameters which
      included the midline estimate of rhythm (mesor). In contrast to the young
      subjects, Cosinor analysis failed to reveal a significant circadian rhythm in
      elderly subjects, for plasma cortisol. In elderly subjects oscillation (mesor) of
      atrial nutriuretic peptide was higher, while that of vasoactive intestinal
      peptide and beta-endorphins was lower. The results suggest changes in the
      physiological secretion of these three peptides in healthy elderly subjects.

PMID- 1386268
TI  - The inhibitory ankyrin and activator Rel proteins.
AB  - The gene families encoding the proteins NF-kappa B, c-Rel and Dorsal, in
      conjunction with their respective inhibitors l kappa B, pp40, and Cactus, achieve
      specificity in gene regulation by means of common principles. The related
      activities of NF-kappa B and Dorsal are mediated by heterodimeric or homodimeric
      complexes of proteins containing the conserved dimerization and DNA-binding
      domain termed Rel. The l kappa Bs and Cactus, which share a core series of
      structural repeats termed ankyrin, inhibit cognate activators through
      differential interactions with the Rel-homology domain. Together, the inhibitory
      ankyrin proteins and their cognate Rel dimers probably define specific signalling
      pathways able to activate specific gene expression. Both gene families include
      proto-oncogenes, thus broadly implicating Rel/l kappa B in the control of both
      normal gene expression and the aberrant gene expression that makes cells
      cancerous.

PMID- 1386269
TI  - The emerging neuropoietic cytokine family: first CDF/LIF, CNTF and IL-6; next
      ONC, MGF, GCSF?
AB  - CDF/LIF is a polyfunctional cytokine that shares a remarkable overlap with
      ciliary neurotrophic factor in its actions on neurons, and with interleukin-6 in
      its actions on other tissues. Moreover, the receptors for this cytokine, as well
      as those for ciliary neurotrophic factor, share homology with the subunits of the
      interleukin-6 receptor. The predicted structural similarity of these proteins
      with oncostatin M, myelomonocytic growth factor and granulocyte colony
      stimulating factor, as well as at least a partial overlap in biological
      activities, is now prompting further examination of their roles in neuronal gene
      expression.

PMID- 1386270
TI  - Trauma, back pain, malingering, and compensation.

PMID- 1386271
TI  - Laparoscopy in urology: perspectives and practice.

PMID- 1386273
TI  - Metastatic carcinoma of the prostate in both testes of patients treated with LH
      RH analogues.

PMID- 1386272
TI  - Phase III randomised study of zoladex versus stilboestrol in the treatment of
      advanced prostate cancer.
AB  - An open randomised Phase III trial was conducted of the depot GnRH analogue
      goserelin (Zoladex) versus stilboestrol (3 mg/day) in patients with advanced or
      metastatic prostate cancer. The study included 250 patients and the median follow
      up was 43 months. In the Zoladex arm the time to first response was achieved
      earlier and more patients reported an improvement in symptoms. There was no
      statistically significant difference between the Zoladex and the stilboestrol
      arms with regard to survival and time to treatment failure. A major reason for
      treatment failure was the preponderance of adverse events in patients receiving
      stilboestrol. It is suggested that stilboestrol should no longer be used for
      prostate cancer when equally effective alternative treatments are available.

PMID- 1386274
TI  - The effect of the NMDA receptor antagonist MK-801 on cerebral blood flow and
      infarct volume in experimental focal stroke.
AB  - The non-competitive N-methyl-D-aspartate receptor/channel antagonist dizocilipine
      maleate (MK-801) has been reported to reduce infarct volume in a variety of focal
      stroke models. We examined the effect of MK-801 on infarct volume and cerebral
      blood flow in temporary and permanent focal ischemia in rats. In Wistar rats
      exposed to permanent right common carotid artery and 2 h of transient right
      middle cerebral and left common carotid artery occlusion followed by 22 h of
      reperfusion, MK-801 reduced infarct volume by 73% (P less than 0.05) and
      significantly increased cerebral blood flow to the ischemic core throughout the 2
      h period of ischemia. In spontaneously hypertensive rats (SHRs) exposed to
      permanent right common carotid artery occlusion and 2 h of transient right middle
      cerebral artery occlusion followed by 22 h of reperfusion, MK-801 decreased
      infarct volume by 13% (P greater than 0.05) and increased cerebral blood flow to
      the penumbral region. In SHRs subjected to permanent right common carotid and
      middle cerebral artery occlusion MK-801 reduced infarct volume by 18% at 3 h (P
      greater than 0.05), by 25% at 6 h (P less than 0.01) and by 18% at 24 h (P less
      than 0.05). MK-801-treated SHRs had no difference in cerebral blood flow to the
      ischemic core, but increased cerebral blood flow to penumbral zones as compared
      with untreated SHRs. These results suggest that the protective effect of MK-801,
      at least in part, relates to improved cerebral blood flow.

PMID- 1386275
TI  - Localization of amyloid precursor protein in GAP43-immunoreactive aberrant
      sprouting neurites in Alzheimer's disease.
AB  - Previous in vitro studies have suggested that amyloid precursor protein (APP)
      could be involved in cell surface adhesion, neuritic growth and survival of
      hippocampal neurons. In the present study, involvement of APP in aberrant
      sprouting in Alzheimer's disease (AD) was studied by comparing immunolabeling
      patterns of anti-APP and anti-growth-associated protein 43 (anti-GAP43). Confocal
      laser imaging of frontal cortex sections double-immunolabeled for APP and GAP43
      showed an increase, in AD, of presynaptic boutons immunostained with anti-GAP43
      that contained anti-APP immunoreactivity. The neuritic plaques in AD cases
      presented intense anti-GAP43 immunoreactive abnormal neurites colocalized with
      anti-APP. Three-dimensional reconstruction of the plaques showed that anti-APP
      was colocalized with anti-GAP43 in 57.5% of the aberrant sprouting neurites. We
      conclude that co-expression of APP with GAP43 in the plaque might be involved in
      the aberrant sprouting response observed in AD.

PMID- 1386276
TI  - Differential effects of excitotoxic basolateral and corticomedial lesions of the
      amygdala on the behavioural and endocrine responses to either sexual or
      aggression-promoting stimuli in the male rat.
AB  - The effects of discrete excitotoxic lesions of the basolateral (BL) and
      corticomedial (CM) amygdaloid areas on both male rat sexual behaviour and inter
      male agonistic behaviour were investigated. The effects of the same lesions on
      the hormonal responses (luteinising hormone (LH) following sexual behaviour,
      corticosterone following aggressive interactions) which accompany these
      behavioural responses were measured. Basolateral lesions had no effect on male
      sexual behaviour but significantly reduced the level of aggressive inter-male
      behaviour. However, the increase in plasma corticosterone concentration which
      occurs after such an interaction was not affected by basolateral lesions. In
      contrast, corticomedial lesions did not affect inter-male offence but severely
      affected copulatory behaviour, including a significant decrease in the males'
      investigation of the receptive female. However, the increase in plasma LH
      concentrations induced by the presence of a receptive female was not affected by
      the CM lesion. These results demonstrate a dissociation between the two
      amygdaloid regions with respect to the contributions made to the two social
      behaviours under study. This anatomical division may reflect differential
      amygdaloid sensory control of these behaviours. A further dissociation between
      amygdaloid contribution to behavioural and hormonal responses was also revealed.
      Neither hormonal response showed a parallel decline with the relevant behavioural
      response, suggesting that neither the basolateral nor corticomedial amygdaloid
      complex is responsible for coordinating behavioural and endocrine responses to a
      specific stimulus.

PMID- 1386277
TI  - Role of 5-hydroxytryptamine receptors on luteinizing-hormone-releasing hormone
      release in the ovariectomized, estradiol-treated rat.
AB  - The present experiments examined the effect of ketanserin [5-hydroxytryptamine-2
      (5-HT2) antagonist] and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (5
      HT1 agonist) on the in vitro release of luteinizing-hormone-releasing hormone
      (LHRH) from the medial basal hypothalamus-preoptic area-suprachiasmatic nucleus
      region (MBH-POA-SCN) of ovariectomized (OVX), estradiol-(E2) treated rats using
      in vitro superfusion techniques. Regularly cycling female Holtzman rats (250-300
      g) were maintained on a photoperiod of 0500-1900 h light at 22 +/- 2 degrees C.
      Rats were ovariectomized (25-30 days) and received Silastic E2 implants (150
      micrograms E2/ml sesame oil) SC 48 h prior to the in vitro superfusion. Following
      a control period of Krebs-Ringer Phosphate (KRP) superfusion, ketanserin (5-HT2
      receptor antagonist, 1 x 10(-6) M) significantly increased LHRH release (p less
      than 0.05). Subsequent superfusion of 5-HT (1 x 10(-8) M) significantly decreased
      (p less than 0.05) the effect of ketanserin on LHRH release. The 5-HT2 antagonist
      Lilly 53857 (1 x 10(-6) M or 1 x 10(-5) M) did not increase LHRH release above
      control levels. Neither 5-HT nor quipazine had a significant effect on LHRH
      release at 1 x 10(-6) M. Superfusion of 8-OH-DPAT (5-HT1 receptor agonist 1 x 10(
      5) M) significantly (p less than 0.01) increased LHRH release but subsequent
      superfusion of 8-OH-DPAT + pindolol (mixed 5-HT1a,1b and a beta-adrenergic
      receptor antagonist, 1 x 10(-6) M) or pindolol alone had no effect on LHRH
      release. These results suggest that the 5-HT1 receptor plays a role in LHRH
      release and this effect may be related to the opposing effects of postsynaptic
      and autoreceptors. However, the failure of Lilly 53857 to reproduce the
      stimulatory effect of ketanserin on LHRH release suggests that 5-HT2 receptors in
      the MBH-POA-SCN may not modify LH release during the estrous cycle.

PMID- 1386278
TI  - Effects of early postnatal sex steroids on acquisition and extinction of a
      continuously reinforced lever-pressing response.
AB  - The effects of early postnatal dihydrotestosterone (DHT) and estradiol on the
      sexually dimorphic continuously reinforced lever-pressing response were
      investigated. 90-day-old male rats postnatally treated (during the first eight
      days of postnatal life) with cyproterone acetate (CA), tamoxifen (TX) or vehicle,
      and 90-day-old females treated with estradiol benzoate (EB), DHT or vehicle in
      the same postnatal period, were studied during the acquisition and extinction of
      the continuously reinforced lever-pressing response using a free-operant
      procedure. During acquisition, the control males made more responses per minute
      than the control females, and also reached the extinction criterion significantly
      sooner than the females. CA treatment impaired the male's performance at the
      levels of that shown by females, whereas TX treatment affected neither
      acquisition nor extinction. Inversely, in both experimental phases females
      treated with DHT performed like control females, whereas the acquisition and
      extinction performances of the EB-females were similar to those obtained in the
      control or TX male groups.

PMID- 1386280
TI  - New agents labelled with technetium 99m for myocardial perfusion imaging.
AB  - New agents labelled with technetium 99m (99mTc) are now available for myocardial
      perfusion imaging. In this article the author reviews the biologic
      characteristics, the imaging protocols and the clinical usefulness of thallous
      chloride Tl 201, 99mTc-sestamibi and 99mTc-teboroxime (not yet available in
      Canada), as well as their complementary roles in the detection of coronary artery
      disease.

PMID- 1386279
TI  - Attenuation of drinking sweetened water following calcium channel blockade.
AB  - Recent reports cite results that both cocaine-induced conditioned place
      preference and activity stimulation are attenuated by pretreatment with the
      calcium channel blocker isradipine (ISR) in rats. By blocking voltage-dependent L
      type calcium channels, ISR may regulate neural dopamine release that, in turn,
      decreases the putative rewarding effects mediated by dopaminergic mechanisms. It
      is known that nonfluid deprived rats avidly consume sweetened fluids; this
      suggests that the sweet taste is rewarding. Three experiments were conducted to
      determine the effects of ISR on drinking sweetened and nonflavored water.
      Experiment 1 was designed to test whether ISR would attenuate the intake of a
      palatable solution in a dose-dependent manner. To this end, ISR was administered
      both peripherally (3.0-30 mg/kg) and centrally (0.3-30 micrograms/rat) prior to a
      solution of saccharin and d-glucose (S + G) being made available to rats (15
      min/day) and intake was recorded. ISR produced dose-dependent decreases (38%-81%)
      in S + G intake dependent on the route of administration. In Experiment 2, water
      intake was measured in 18 h water-deprived rats following ISR (10 mg/kg)
      administration as well as comparing S + G drinking. The effect of two ISR
      vehicles, dimethyl sulfoxide and Tween 80, upon fluid intake was also determined.
      ISR injection did not attenuate water intake in 18 h water-deprived rats and the
      choice of vehicle did not affect the ISR-induced attenuation of S + G drinking.
      In Experiment 3, a single dose (30 micrograms) of ICV administered ISR, that
      attenuated S + G intake by approximately 44%, did not attenuate water intake in
      18 h water-deprived rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386281
TI  - Pseudoulcerating mass of the esophagus caused by cardiomegaly.

PMID- 1386282
TI  - Oral ondansetron for the control of delayed emesis after cisplatin. Report of a
      phase II study and a review of completed trials to manage delayed emesis.
AB  - BACKGROUND: Despite excellent control of vomiting during the initial 24 hours
      after chemotherapy with combination antiemetics, most patients who receive
      cisplatin at doses of 120 mg/m2 experience delayed emesis 24-120 hours after
      chemotherapy. METHODS: Twenty patients receiving cisplatin (greater than or equal
      to 100 mg/m2) as initial chemotherapy were entered into this Phase II trial to
      test the effectiveness of oral ondansetron, a specific serotonin receptor (5-HT3)
      antagonist, in controlling delayed emesis. All patients received intravenous
      metoclopramide, dexamethasone, and lorazepam for the control of acute emesis 0-24
      hours after receiving cisplatin. They then received ondansetron 16 mg orally
      three times a day for 4 days. RESULTS: Fifteen percent of those who were treated
      with oral ondansetron had complete control of delayed emesis during the entire 4
      day period (95% confidence interval, 3-38%). No serious adverse events occurred.
      CONCLUSIONS: At the dose and schedule tested, oral ondansetron did not appear to
      control delayed emesis. Previous trials of programs to lessen this complication
      suggest that both metoclopramide and dexamethasone are effective in lessening
      delayed vomiting and that the combination of these drugs is more effective than
      placebo. Although in one trial ondansetron appeared to control delayed emesis in
      patients who received cisplatin at doses of 50-120 mg/m2, it was not superior to
      either placebo or metoclopramide in two randomized studies. Additional testing of
      the 5-HT3 antagonists, both alone and in combination, will be needed to establish
      their role in the management of this condition.

PMID- 1386284
TI  - Impact of polydonor mixed lymphocyte culture media on quantity and quality of
      myeloid metaphases.
AB  - A novel mitotic stimulator of myeloid hematopoietic cells was prospectively
      evaluated to detect enhanced quantity and quality of metaphases from bone marrow
      (BM) cultures for cytogenetic analysis. This polydonor mixed lymphocyte
      conditioned (PMLC) media decreased the culture failure rate, improved detection
      of chromosomal aberrations, and reduced technologists' analysis time. The
      conditioned media is recommended as a highly effective culture system for normal
      and neoplastic cells of myeloid lineage.

PMID- 1386283
TI  - Recent developments in endocrine treatment of prostate cancer.
AB  - Cancer of the prostate gland is the most frequently occurring malignant lesion in
      men. Because most prostate cells depend on androgen for growth, removal of
      testosterone by either orchiectomy or medical castration using diethylstilbestrol
      or a luteinizing hormone-releasing hormone (LHRH) analogue is first-line
      treatment for patients with symptomatic Stage D2 disease. The trend in hormonal
      therapy has been toward long-acting minimal-dosing high-compliance regimens,
      capitalizing on the recent availability of the long-acting LHRH analogues, which
      require only monthly injections to maintain castration levels of testosterone,
      and the nonsteroidal antiandrogen ICI 176,334, which (in early clinical trials)
      appears to block intracellular testosterone activity with a once-a-day oral
      regimen. To eliminate the rapid LH increase that can occur during early agonist
      therapy, combinations of LHRH analogues and antiandrogens (total androgen
      blockade) have been tested and appear promising. The effects of hormonal
      treatment in patients with symptomatic Stage D2 prostate cancer have been studied
      extensively and are relatively well understood. By contrast, hormonal treatment
      has not been explored in contemporary randomized Phase III trials of asymptomatic
      Stage D2, D1, or C disease, localized Stage B or A disease, or before prostate
      surgery or radiation treatment. Research must continue to determine the optimal
      regimen that suppresses testosterone activity with the least amount of toxicity.

PMID- 1386285
TI  - Interactions between p21ras proteins and their GTPase activating proteins.
AB  - Two proteins that regulate p21ras GTPase activity have been identified. These
      proteins interact with a region of ras p21 that is necessary for p21ras function
      and may themselves be components of signalling complexes. The first of these
      proteins to be identified, GAP, contains domains that interact with receptor
      tyrosine kinases and other tyrosine phosphoproteins, providing a direct link
      between signalling pathways involving these proteins and p21ras. The second, the
      product of the NF1 gene, is less well characterized but seems to connect p21ras
      to other signalling pathways which are perturbed in the NF1 disease. The ability
      of p21ras to interact with GAP may be compromised by competitive binding to the
      product of the Ki-rev1 gene, p21rap1. This competition for binding to GAP, or
      other proteins that interact with the effector site of ras p21, may explain the
      ability of Ki-rev1 to suppress cellular transformation by ras oncogenes.

PMID- 1386286
TI  - Lymphokine production by human melanoma tumor-infiltrating lymphocytes.
AB  - Lymphokine production by human melanoma tumor-infiltrating lymphocytes (TIL) was
      studied. Uncultured TIL produced interferon gamma (IFN gamma), but not
      interleukin-2 (IL-2) or IL-4, in response to anti-CD3 mAb or IL-2. In bulk
      cultures, IL-2-activated TIL displaying autologous tumor-specific cytotoxicity
      (CTL-TIL) produced IFN gamma in culture with medium alone, whereas IL-2-activated
      noncytotoxic TIL did not. Addition of anti-CD3 mAb or autologous tumor cells up
      regulated IFN gamma production in IL-2-activated TIL from 10 of 12 or 6 of 12
      cases respectively. Those from 4 of 12 cases (2 CTL-TIL and 2 noncytotoxic TIL)
      produced IL-2 in culture with medium alone. At the clonal level, 5 (4 CD4+ and 1
      CD8+) of 7 autologous tumor-specific CTL clones derived from TIL and 3 (2 CD4+
      and 1 CD8+) of 7 noncytotoxic TIL clones produced IFN gamma in culture with
      medium alone, which was up-regulated by adding anti-CD3 mAb. Two IFN gamma
      producing CTL clones tested produced IL-2 in 4x-concentrated supernatants from a
      3.5-h culture with medium alone. Furthermore, 2 IFN gamma-producing CTL clones
      tested expressed mRNA for both IFN gamma and IL-2. IL-2 production and its mRNA
      expression were up- or down-regulated, respectively, by adding anti-CD3 mAb or
      autologous tumor cells. IL-4 production was not observed in culture either with
      medium alone or with IL-2 in any of the cells described above. Anti-CD3 mAb was
      required for IL-4 production in 3 of 12 IL-2-activated TIL, 2 of 6 CTL clones,
      and none of 5 noncytotoxic TIL clones. In summary, IFN gamma production was
      characteristic of melanoma TIL. Some autologous tumor-specific CTL in TIL are
      suggested to be productive of IL-2 and IFN gamma under unstimulated conditions,
      both being required for self-activation in an autocrine loop.

PMID- 1386287
TI  - Pharmacologic treatment of osteoarthritis.
AB  - Current pharmacotherapy for osteoarthritis (OA) is aimed at relief of pain and
      functional disability. Although an inflammatory component may be found in some
      cases, there is little evidence that anti-inflammatory drugs commonly used in the
      treatment of OA provide more relief than simple analgesics. A growing body of
      knowledge about the pathophysiology of OA now offers opportunities to develop
      interventions aimed at retarding the progressive degeneration of articular
      cartilage. This is a function of an imbalance between cartilage matrix synthesis
      and breakdown. New and experimental treatments include oral, parenteral, and
      intra-articular agents, some of which are chemicals and others biological
      products. Their modes of action have generally not been established in humans,
      but may be inferred from in vitro culture systems and animal models. These
      mechanisms include inhibition of synovial cell-derived cytokines and chondrocyte
      derived degradative enzymes, inactivation of superoxide free radicals,
      stimulation of matrix synthesis, and enhancement of synovial fluid lubrication.
      Many of these treatments have been shown to provide short- or long-term
      symptomatic improvement in clinical trials. Protection of cartilage or promotion
      of repair has been demonstrated in animal studies, but not convincingly in human
      OA studies.

PMID- 1386288
TI  - Annexin VI is required for budding of clathrin-coated pits.
AB  - Isolated plasma membranes attached to a solid substratum at 4 degrees C have
      numerous clathrin-coated pits. These pits initially are flat but become deeply
      invaginated after warming to 37 degrees C. The pits remain tethered to the
      membrane in this rounded condition unless supplied with ATP, Ca2+, and cytosol.
      We now show that when cytosol is treated to remove the Ca(2+)-dependent,
      phospholipid-binding protein annexin VI, coated pit budding no longer takes
      place. Addition of purified annexin VI back to the annexin VI-depleted cytosol
      restores budding activity to normal. Purified annexin VI alone shows only a
      modest budding activity, suggesting that the cytosol contains a factor(s) in
      addition to annexin VI that is required for full activity. Cytosol-dependent
      activation of annexin VI requires both ATP and Ca2+. Annexin VI appears to be not
      only an active component in the detachment of coated pits from the membrane but
      also a site for regulating the formation of coated vesicles.

PMID- 1386289
TI  - A protein tyrosine kinase in the interferon alpha/beta signaling pathway.
AB  - The mutant human cell line 11.1 is unresponsive to interferon alpha. Here we
      describe the genetic complementation of this mutant and the identification and
      cloning of the wild-type gene that corrects the defect. Using transfection with
      genomic DNA in conjunction with a powerful back-selection, we isolated a cosmid
      that reverts the mutant phenotype of 11.1 cells. The cosmid encodes a single
      message whose level is greatly reduced in mutant cells. Complementary DNAs were
      cloned and found to be virtually identical to tyk2, a human mRNA encoding a non
      receptor protein tyrosine kinase of previously unknown function. This finding
      shows that tyk2 links the interferon alpha/beta receptor to the cytoplasmic
      transcription factor that mediates activation of interferon-responsive genes.

PMID- 1386290
TI  - Disease, illness and health: theoretical models of the disablement process.
AB  - Handicap is the result of a process of disablement whose origin is a pathological
      condition (disease). According to some definitions of health (e.g., a state of
      complete physical, mental and social well-being), the classical biomedical
      concept is too restrictive to cover all the consequences of disease. New models
      have been proposed: the impairment-disability-handicap model presented by WHO,
      the situational handicap model, and the quality-of-life model. A unifying schema
      of the disablement process includes these concepts and provides a useful way of
      analysing the consequences of disease. Factors that modify the disablement
      process can be identified by their respective impacts, and provide operational
      guidelines for public health interventions.

PMID- 1386291
TI  - Plasma atrial natriuretic peptide is unstable under most storage conditions.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) is a hormonal regulator of
      cardiovascular fluid volume. More than 1,000 scientific articles were written
      about ANP between 1987 and 1991. Because some articles hinted at problems with
      storing ANP, this study examined the effect of numerous techniques for storing
      and processing human ANP samples. METHODS AND RESULTS: Samples were obtained
      repeatedly from three patients, treated, and stored under a variety of
      conditions. Experiment 1 evaluated the effects of different preservatives at 35,
      21, 14, 10, and 7 days before assay. Experiment 2 evaluated nonspecific binding
      of ANP to different storage tubes during 28 days of storage. Experiment 3
      evaluated the effect of storage at -20 degrees C, -80 degrees C, and -196 degrees
      C for 1 month. ANP was very unstable, degrading as much as 30% after 3 days of
      storage and by more than 50% in 1 month even when stored at -80 degrees C. Only
      storage at -196 degrees C (in liquid nitrogen) kept ANP stable for 1 month.
      Extraction and lyophilization of the samples before freezing and assay within 7
      days of freezing only partially minimized the amount of degradation. All other
      processing techniques had little effect on slowing the degradation of ANP.
      CONCLUSIONS: These findings raise disturbing questions about the interpretation
      of the substantial literature on ANP.

PMID- 1386292
TI  - Lipoprotein(a) is an independent risk factor for cardiovascular disease in
      hemodialysis patients.
AB  - BACKGROUND: Although serum lipoprotein(a) [Lp(a)] is an independent risk factor
      for atherosclerosis in the general population and Lp(a) levels are increased in
      hemodialysis patients, an association of Lp(a) with the risk of clinical events
      attributed to atherosclerosis has not been established in the chronic
      hemodialysis patient population. We therefore determined the association between
      Lp(a) levels and the risk of clinical events of presumed atherosclerotic etiology
      in a prospective study of an outpatient hemodialysis population. METHODS AND
      RESULTS: Lp(a) was measured by radioimmunoassay in a baseline cardiovascular
      disease risk assessment in a consecutive series of 129 hemodialysis patients. The
      relation between baseline Lp(a) and clinical events of presumed atherosclerotic
      etiology was determined during 48 months of follow-up. Hemodialysis patients had
      a median Lp(a) concentration that was approximately four times as high as the
      median Lp(a) concentration in normal controls and twice as high as the levels in
      controls with angiographic evidence of coronary artery disease [median Lp(a),
      38.4 versus 16.9 mg/dl; p less than 0.001]. Baseline Lp(a) levels were no
      different in participants with or with no history of a previous clinical event at
      the time of the baseline examination. However, baseline Lp(a) concentration (p
      less than 0.001) and a history of atherosclerotic clinical events (p = 0.001)
      were associated with clinical events during the period of follow-up. In contrast,
      baseline serum total cholesterol, triglyceride, high density lipoprotein
      cholesterol, low density lipoprotein cholesterol, age, gender, race, or duration
      of hemodialysis were unrelated to this risk in the prospective study. Stepwise
      multiple logistic regression analysis demonstrated that serum Lp(a) concentration
      (p = 0.001) and the presence of a previous clinical event (p = 0.004) were the
      only independent contributors to the risk of a clinical event during the period
      of follow-up. CONCLUSIONS: Lp(a) is an independent risk factor for clinical
      events attributed to atherosclerotic cardiovascular disease in patients receiving
      chronic hemodialysis treatment of end-stage renal disease.

PMID- 1386293
TI  - Effect of balloon angioplasty on femoral artery evaluated with intravascular
      ultrasound imaging.
AB  - BACKGROUND: Intravascular ultrasound was used to assess the immediate effect of
      balloon angioplasty on the superficial femoral artery. METHODS AND RESULTS: In 16
      consecutive patients, corresponding ultrasonic cross sections (n = 72) before and
      after balloon angioplasty were qualitatively and quantitatively analyzed. The
      qualitative data were compared with angiographic findings. Before intervention,
      the angiographically demonstrated obstructive lesions were confirmed by
      intravascular ultrasound. Ultrasound enabled discrimination between soft (n = 43)
      and hard (n = 29) lesions, as well as between eccentric (n = 57) and concentric
      (n = 15) lesions. After balloon angioplasty, the presence of a dissection
      assessed angiographically in 14 patients was confirmed by intravascular
      ultrasound. Additional morphological information provided by ultrasound included
      plaque rupture in 14 patients and internal lamina rupture in six patients.
      Quantitative ultrasound data revealed an increase in free lumen area from 9.7 +/-
      4.7 to 18.3 +/- 7.0 mm2 (p less than or equal to 0.01), an increase in minimal
      lumen diameter from 2.8 +/- 0.7 to 3.6 +/- 1.2 mm (p less than or equal to 0.01),
      and an increase in media-bounded area from 21.7 +/- 5.4 to 28.3 +/- 5.8 mm2 (p
      less than or equal to 0.01). The lesion area for the majority of cases (n = 32)
      remained unchanged (13.0 +/- 4.9 mm2 versus 12.9 +/- 4.6 mm2), or the lesion
      disappeared partially (from 9.1 +/- 0.9 to 4.3 +/- 1.4 mm2, n = 4, p less than or
      equal to 0.01) or totally (from 10.1 +/- 4.2 to 0 mm2, n = 6). Stretching of the
      arterial wall was further evidenced by medial thinning from 0.55 +/- 0.19 to 0.34
      +/- 0.11 mm (p less than or equal to 0.01). CONCLUSIONS: Luminal enlargement by
      balloon dilatation is achieved primarily by overstretching the arterial wall,
      with the lesion volume remaining practically unchanged. Overstretching is
      accompanied almost always by dissection and plaque rupture and occasionally by an
      internal lamina rupture.

PMID- 1386294
TI  - The expression of GAP43 mRNA during the late embryonic and early postnatal
      development of the CNS of the rat: an in situ hybridization study.
AB  - GAP43 is a developmentally regulated phosphoprotein which is almost exclusively
      found in neurons. Numerous correlative studies have shown that GAP43 is expressed
      at high levels during neurite extension, axonal elongation and synaptogenesis. In
      this study we used in situ hybridization to examine GAP43 expression during late
      embryonic and early postnatal development. The highest relative levels of GAP43
      at all stages were present in the neocortex. Levels in this and other regions
      peaked between postnatal days 5 and 10. These results indicate that high levels
      of GAP43 mRNA correlate most highly with the latter stages of axon outgrowth and
      with the early stages of synapse formation.

PMID- 1386295
TI  - Effect of anaesthesia and acute intestinal ischemia on serum beta-N
      acetylhexosaminidase activity in rabbit as biological model.

PMID- 1386296
TI  - Cyclophosphamide treatment antagonizes the in vitro development of Mycobacterium
      lepraemurium-induced suppressor cell precursors.
AB  - The in vitro-inducible maturation of splenic suppressor cell precursors detected
      during the early phase of Mycobacterium lepraemurium infection can be abrogated
      when a high dose of cyclophosphamide (Cy) is inoculated to infected mice 2 days
      before assay. The drug does not act directly on adherent suppressor cell
      precursors, but rather inhibits their activation by a non-adherent cell subset
      whose phenotype has not yet been elucidated. It was established by flow cytometry
      analyses, that despite a marked increase in the total number of splenic non
      adherent cells following M. lepraemurium infection, the effect of Cy on Ia+, Thy
      1+, CD4+ and CD8+ cells in infected mice was comparable to that observed in
      normal controls. It was not possible to determine the duration of the inhibiting
      effect of Cy on non-adherent regulatory cells, because the drug was itself
      inducing suppressor cells from 7 days after inoculation. By the time spleen cell
      suspensions were totally free of Cy-induced suppressor cells, infection-dependent
      suppressor cell precursors were once again detected, indicating that Cy treatment
      did not prevent their in vivo accumulation. Therefore, even though M.
      lepraemurium-induced adherent suppressor cell precursors are themselves fully
      resistant to Cy, their development is transiently abrogated by the drug, most
      probably through the impairment of a non-adherent cell subset regulating their
      maturation.

PMID- 1386297
TI  - Analysis of T cell receptors in rheumatoid arthritis: the increased expression of
      HLA-DR antigen on circulating gamma delta+ T cells is correlated with disease
      activity.
AB  - The phenotypic characteristics of peripheral blood T cells, isolated from 37
      rheumatoid arthritis (RA) patients and 17 healthy controls were determined with
      special emphasis on gamma delta+ T cells and CD4-CD8- alpha beta+ T cells. Two-
      and three-colour automated flow cytometry analyses were performed using a panel
      of MoAbs directed against differentiation antigens and T cell receptor molecules.
      The results demonstrated: (i) no significant difference between the percentages
      of CD4-CD8- alpha beta+ T cells in patients and controls; (ii) a significant
      decrease of the gamma delta+ T cell level in the peripheral blood of RA patients
      relative to controls; (iii) phenotypic abnormalities of circulating gamma delta+
      T cells in RA patients suggestive of an activation status in vivo. These
      abnormalities included a significant reduction in the density of the T cell
      differentiation antigen CD3 and an increase in the expression of HLA-DR antigen.
      The level of circulating HLA-DR+/gamma delta+ T cells was significantly higher in
      patients with active disease. HLA-DR+/gamma delta+ T cells were also present in
      the synovial fluid obtained from three patients with an active disease. In
      addition, preliminary experiments showed that the activated gamma delta+ T cells
      were predominantly V delta 1. Taken together, these data support the involvement
      of gamma delta+ T cells in the pathogenesis of RA.

PMID- 1386298
TI  - A persistent T cell expansion in the peripheral blood of a normal adult male: a
      new clinical entity?
AB  - A dramatic and persistent T cell expansion in a healthy adult male was initially
      identified, using anti-T cell receptor for antigen (TCR)-specific MoAbs. The
      expanded T cells were found to be expressing TCR containing V alpha 12.1 and V
      beta 5.2, and they composed approximately one third of all the CD8+ T cells. The
      cells were shown to be not only non-activated (HLA-DR-, IL-2R-) but also of
      'virgin' cell type (CD45RA+/CD45RO-) and they persisted over the observation
      period of more than one and a half years. Various T and B cell markers, and all
      other laboratory and physical parameters analysed, were normal. The expanded CD8+
      T cells were further characterized by polymerase chain reaction (PCR)
      amplification, using V beta- and C beta-specific primers, followed by
      hybridization with J beta-specific probes. Close to 90% of the V alpha 12.1+ V
      beta 5.2+ T cells were found to utilize the J beta 2.5 gene segment, thus
      strongly suggesting the expanded T cells to be monoclonal. The condition may
      constitute a T cell counterpart to 'monoclonal gammopathy of undetermined
      significance' (MGUS), and by analogy we suggest it should be designated
      'monoclonal T cell expansion of undetermined significance' (MTUS).

PMID- 1386300
TI  - Bispecific anti-human red blood Rhesus-D antigen x anti Fc gamma RI targeted
      antibody-dependent cell-mediated cytotoxicity and phagocytosis by mononuclear
      leucocytes.
AB  - The Fc receptor mediated antibody-dependent cell-mediated cytotoxicity (ADCC) and
      phagocytosis induced by bispecific antibody (BsAb) to the high-affinity Fc
      receptor for IgG (Fc gamma RI) and to human red blood group antigen RhD were
      studied in vitro, using human mononuclear leucocytes as effector cells. The
      results were compared with those obtained by using a human monoclonal IgG1 anti
      RhD used alone and a reference human polyclonal anti-RhD antibody. The effect of
      non-specific human IgG on FcR-mediated functions by mononuclear leucocytes was
      checked. The results demonstrate that BsAb presents a high resistance of Fc
      mediated function to blockade by non-specific human IgG compared with that of
      both polyclonal and monoclonal anti-RhD antibodies. These results further
      encourage possible clinical application of bispecific antibody in passive
      immunotherapy.

PMID- 1386299
TI  - Preferential activation of peripheral blood V gamma 9+ gamma/delta T cells by
      group A, B and C but not group D or F streptococci.
AB  - Previous studies have established that inactivated mycobacteria are potent and
      selective activators of V gamma 9+/V delta 2+ human gamma/delta T cells. Here we
      have analysed the proliferative response of human gamma/delta T cells to five
      serologically distinct groups of streptococci. While heat-inactivated
      streptococci of all five serogroups tested (A, B, C, D and F) induced a strong
      proliferative response in peripheral blood mononuclear cells (PBMC), only groups
      A, B and C elicited a selective activation of V gamma 9+ gamma/delta T cells in
      10 (serogroup B) or 11 (serogroups A and C) of 11 tested healthy individuals. In
      striking contrast, groups D and F streptococci failed to activate gamma/delta T
      cells in nine of 11 donors and induced only a weak gamma/delta T cell response in
      two additional individuals. Depletion of V gamma 9+ T cells before culture
      completely eliminated all gamma/delta T cell responses to streptococci. These
      data indicate that groups A, B and C (but not D or F) streptococci can be
      included in the growing list of selective ligands for V gamma 9+/V delta 2+ human
      gamma/delta T cells.

PMID- 1386301
TI  - Dynamic simultaneous anterior and posterior imaging of transplant and native
      renal function using dual-headed gamma camera.
AB  - The authors describe the nonvisualization of a renal transplant on DTPA scan with
      late visualization of activity within the bladder in a 27-year-old patient with
      diabetes. Origin of bladder activity was later clarified by dynamic anterior and
      posterior imaging using MAG 3 and an extra large field-of-view, dual-headed gamma
      camera.

PMID- 1386302
TI  - Does increased life expectancy imply active life expectancy?
AB  - From Danish results, it is argued that longer life need not imply worse health.
      If we as individuals and society will prevent the "pawnbroker-diseases," increase
      access to geriatric rehabilitation, and supply necessary services in an
      individualised way, most added years can be active years. The following
      conclusions are drawn: In the first decades after the year 2000, morbidity,
      disability and mortality will be postponed, but treatment will be more important
      for prolongation of life than prevention. Therefore, the net result will be
      extension of morbidity. The next question is how severe disability will be among
      the increased number of people who have a disease, but are not dying from it. The
      elderly will be more healthy in the future, but the prevalence of chronic
      disabling diseases may not change, or may even increase. That is because healthy
      men and women can postpone disability and death until higher ages (successful
      aging), but some elderly persons live with premature disabling diseases, which
      might have killed them some decades ago. When elderly people make the transition
      from autonomy to dependence in the course of a disease, it is possible by early
      geriatric intervention and rehabilitation to restore them to functional levels
      and provide them with more active years. It is possible to disseminate geriatric
      rehabilitation to a much wider population of elderly with multipathology and
      social problems. In this way, disability can be overcome in a higher fraction of
      diseased elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386304
TI  - Evidence for atrial natriuretic peptide-(5-28) production by rat placental
      cytotrophoblasts.
AB  - Atrial natriuretic peptide (ANP), a 28-amino acid peptide, is produced and
      secreted by cardiac atriocytes to modulate cardiovascular and renal functions. We
      report here the production of ANP-(5-28) and its 15K mol wt (M(r)) presumptive
      precursors by cytotrophoblasts of rat placentae. Placental tissues were collected
      from Sprague-Dawley fetal rats on days 12, 16, 18, and 20 of gestation and acid
      extracted for immunoreactive (ir) ANP assay. The contents of placental irANP
      increased over the course of fetal growth, with the highest amount (mean +/- SE,
      1083 +/- 125 pg/tissue; n = 7) found near term. Sephadex G-50 gel chromatographic
      profiles of the placental extract revealed a major peak of irANP coeluted with
      the 3K M(r) of synthetic rat (r) ANP-(1-28) and a minor peak in the position
      consistent with that of 15K M(r). HPLC analysis of the 3K M(r) species showed a
      single peak of immunoreactivity, which eluted with a retention time similar to
      that of rANP-(5-28). In placental sections, irANP and pro-ANP mRNA were localized
      by immunoperoxidase staining and colorimetric in situ hybridization in a
      subpopulation of placental cytotrophoblasts, but not in syncytiotrophoblasts or
      chorionic cells. Northern blot analysis showed a single band of pro-ANP mRNA in
      rat placental tissues similar in size to that found in the heart (approximately
      0.85 kilobases), with the highest level of pro-ANP mRNA signal detected in the
      placentae of 16-day gestation fetuses. Our findings suggest that ANP is expressed
      and produced by a small population of rat placental cytotrophoblasts and that the
      15K M(r) precursor peptide is extensively processed into the N-terminal-truncated
      form of ANP-(5-28) in the tissue.

PMID- 1386303
TI  - Elevated 4-hydroxylation of estradiol by hamster kidney microsomes: a potential
      pathway of metabolic activation of estrogens.
AB  - Characterization of enzymes mediating the formation of catecholestrogens (CE) by
      hamster kidney is of importance because of the proposed role of CE in renal
      cancer induced in this species by estrogens. We have reexamined the potential of
      hamster kidney to convert estradiol (E2) to 2- and 4-hydroxylated CE because of
      recent evidence of the limitations of assays used in previous studies, in
      particular in measuring 4-hydroxylation of estrogens. Under conditions optimized
      for NADPH-dependent activity, hamster kidney microsomes exhibited high levels of
      both E2-2- and E2-4-hydroxylase activities. Evidence that the two activities
      depend on different forms of cytochrome P-450 was obtained by the demonstration
      that 2- and 4-hydroxylation of E2 were affected differentially 1) by chronic
      treatment of hamsters with E2 and 2) by fadrozole hydrochloride, a selective
      cytochrome P-450 inhibitor. NADPH-dependent 2-hydroxylation of E2 from control
      and E2-treated hamsters, measured by a direct product isolation assay, was 1
      order of magnitude higher (apparent maximum velocity, 24-32 and 6-12.5 pmol/mg
      protein.min in control and E2-treated hamsters, respectively) than that reported
      previously using radioenzymatic assays. NADPH-dependent 4-hydroxylation of E2 in
      controls approached and in E2-treated hamsters exceeded 2-hydroxylation of E2
      (apparent maximum velocity, 17-21 and 7.5-19 pmol/mg protein.min in control and
      E2-treated hamsters, respectively). Thus, estrogen treatment reversed the ratios
      of NADPH-dependent E2-2-/4-hydroxylase activities by causing a much greater
      decline in 2- than 4-hydroxylation of E2 (P less than 0.007, by analysis of
      variance). Fadrozole hydrochloride caused a marked dose-dependent decrease in 2
      hydroxylation of E2, in contrast to a small nondose-dependent inhibition of 4
      hydroxylation. Under conditions optimized for peroxidatic organic hydroperoxide
      dependent activity, hamster kidney microsomes generated 2- and 4-hydroxylated CE
      in similar amounts. The amounts of the two CE and, consequently, the ratios
      remained unaffected by estrogen treatment (1:0.9 and 1:1.0 in control and E2
      treated hamsters, respectively). Thus, this study establishes that CE can be
      generated in the same tissue by three different pathways, i.e. NADPH-dependent E2
      2-hydroxylase, NADPH-dependent E2-4-hydroxylase, and organic hydroperoxide
      dependent E2-2/4-hydroxylase activities. We also show that these three activities
      can be regulated differentially and are, thus, probably mediated by different
      forms of cytochrome P-450. In hamster kidney, the potential to generate 4
      hydroxylated CE metabolites with distinct properties could be a factor in this
      tissue's vulnerability to estrogen-induced carcinogenesis.

PMID- 1386305
TI  - A desiccation-related Elip-like gene from the resurrection plant Craterostigma
      plantagineum is regulated by light and ABA.
AB  - The resurrection plant Craterostigma plantagineum tolerates an extreme loss of
      cellular water. Therefore this plant is being studied as model system to analyse
      desiccation tolerance at the molecular level. Upon dehydration, new transcripts
      are abundantly expressed in different tissues of the plant. One such desiccation
      related nuclear gene (dsp-22 for desiccation stress protein) encodes a mature 21
      kDa protein which accumulates in the chloroplasts. Sequence analysis indicates
      that dsp-22 is closely related to early light inducible genes (Elip) of higher
      plants and to a carotene biosynthesis related gene (cbr) isolated from the green
      alga Dunaliella bardawil. In contrast to other desiccation-related genes, light
      is an essential positive factor regulating the expression of dsp-22: ABA-mediated
      gene activation leads to the accumulation of the transcript only in the presence
      of light. During the desiccation process, light acts at the transcriptional and
      post-transcriptional levels. The implications of these different controls and the
      possible role of the dsp-22 protein in the desiccation/rehydration process are
      discussed.

PMID- 1386306
TI  - Sensory mother cell division is specifically affected in a Cyclin-A mutant of
      Drosophila melanogaster.
AB  - Cyclin proteins are one of the important components of the mechanism regulating
      mitosis in eukaryotic cells. We isolated a Drosophila Cyclin-A mutant in which
      the progenitor cells of the peripheral nervous system (the sensory mother cells)
      do not divide properly, causing the loss and other abnormalities of
      mechanosensory organs in the adult fly. Sequence analysis of the mutant genome
      reveals that a P element is inserted into the first intron of the Cyclin-A gene.
      A 13 kb wild-type genomic DNA containing the Cyclin-A transcription units rescued
      the mutant phenotype when introduced into the mutant fly. The regulation of cell
      type specific expression of the Cyclin-A gene is discussed.

PMID- 1386308
TI  - Solubility and posttranslational regulation of GP130/F11--a neuronal GPI-linked
      cell adhesion molecule enriched in the neuronal membrane skeleton.
AB  - GP130 (renamed contactin) has previously been identified by its detergent
      insolubility and retention with the actin-containing "membrane skeleton" isolated
      from chicken neurons and brain. The contactin sequence predicted a transmembrane
      and cytoplasmic domain for the molecule. Recently, F11 was shown to have an
      identical sequence except for the C terminus, and it was predicted to be linked
      to the plasma membrane by a glycosylphosphatidylinositol (GPI) group. Here we
      describe that GP130 can be released both from brain membranes and the detergent
      insoluble membrane skeleton by a phosphoinositol-specific phospholipase C (PI
      PLC) indicating that F11 and GP130/contactin are probably identical and that
      surprisingly the lipid anchor is partly or totally responsible for its non-ionic
      detergent insolubility. The "membrane skeleton" is a rich source of GPI-linked
      glycoproteins as judged by 1) most glycoproteins can be released by a PI-PLC and
      2) most [3H]ethanolamine-labeled glycoproteins are present in, or enriched in the
      membrane skeleton. Thus, detergent insolubility appears to be a characteristic of
      GPI-anchored glycoproteins. No evidence has been obtained that GP130/F11 is
      released or secreted in vivo or in culture. In addition, GP130/F11 has an
      unusually long half-life in culture of greater than 3 days. The structure of the
      neuronal membrane skeleton and the potential function of GPI-anchored
      glycoproteins is discussed.

PMID- 1386309
TI  - Risk of cardiac events (in patients with established ischaemic heart disease).

PMID- 1386307
TI  - Lac repressor with the helix-turn-helix motif of lambda cro binds to lac
      operator.
AB  - Lac repressor, lambda cro protein and their operator complexes are structurally,
      biochemically and genetically well analysed. Both proteins contain a helix-turn
      helix (HTH) motif which they use to bind specifically to their operators. The DNA
      sequences 5'-GTGA-3' and 5'-TCAC-3' recognized in palindromic lac operator are
      the same as in lambda operator but their order is inverted form head to head to
      tail to tail. Different modes of aggregation of the monomers of the two proteins
      determine the different arrangements of the HTH motifs. Here we show that the HTH
      motif of lambda cro protein can replace the HTH motif of Lac repressor without
      changing its specificity. Such hybrid Lac repressor is unstable. It binds in
      vitro more weakly than Lac repressor but with the same specificity to ideal lac
      operator. It does not bind to consensus lambda operator.

PMID- 1386310
TI  - Ischaemic heart disease: risk stratification and intervention. Risk of
      progression of coronary artery disease.

PMID- 1386311
TI  - Lymphokine profile and activation pattern of two unrelated antigen- or idiotype
      specific T suppressor cell clones.
AB  - Two T suppressor (Ts) clones of different specificity have been analyzed for
      their lymphokine spectrum. BVI/5 is an I-Ek-restricted bovine serum albumin (BSA)
      specific Ts cell clone from a CBA/J mouse tolerized by low doses of BSA. It
      affects directly or indirectly the function of BSA-specific T helper (Th) cells.
      The Ts cell clone 178-4 from a BALB/c mouse is I-Ed restricted and recognizes the
      public J558 Id on B cells. It prevents alpha(1----3)dextran B 1355S (Dex)
      specific IgG antibody production and drives Dex-specific J558 idiotype-bearing B
      cells into an anergic B IgG memory cell state. Both Ts cell clones thus cause
      specific suppression, yet in different experimental systems using different
      effector mechanisms. Upon stimulation with concanavalin A or fixed CD3-specific
      monoclonal antibody, both clones produce high levels of interferon (IFN)-gamma
      and tumor necrosis factor (TNF) but in contrast to Th1 cells no interleukin (IL)
      2. Both clones produce low levels of IL-3 and IL-6 but no IL-4, IL-5 and IL-9.
      Furthermore, unlike Th2 cells, both clones do not respond to IL-1. The mechanism
      of the idiotype-specific induction of anergy in Dex-specific B IgG memory cells
      by 178-4 Ts cells is not yet understood. BVI/5 Ts cells suppress in vitro the BSA
      specific proliferation of the BSA-specific Th cell clone 83/1, as well as the
      response of BSA-primed CBA/LN cells. Whereas the suppressive effect on 83/1 cells
      is due to IFN-gamma alone the suppression of BSA-specific lymph node cells can be
      simulated neither by IFN-gamma nor the combination of IFN-gamma and TNF. Thus
      these mediators cannot account for the antigen-specific suppression by BVI/5 Ts
      cells in polyclonal in vitro responses from lymph node cells and probably not for
      the induction of in vivo unresponsiveness.

PMID- 1386313
TI  - Immunobiological studies on experimental visceral leishmaniasis. II. Adherent
      cell-mediated down-regulation of delayed-type hypersensitivity response and up
      regulation of B cell activation.
AB  - Visceral leishmaniasis or kala-azar is characterized by a variety of
      immunopathological consequences in man. The most remarkable of these are the
      depression of cell-mediated immunity and polyclonal B cell activation. The
      consequences observed in man could be induced in a murine model by inoculating
      the causative agent, Leishmania donovani. The cell-mediated response was studied
      in this murine model in terms of the delayed-type hypersensitivity (DTH) response
      toward leishmania antigen in a progressive infection. BALB/b (H-2b) mice showed
      progressive enhancement in the DTH response, whereas BALB/c (H-2d) mice showed
      strong DTH at the onset which gradually disappeared (defined as DTH-negative
      phase) and reappeared again at the later stage of infection. Adoptive transfer of
      enriched populations of splenic T cells from infected BALB/c mice together with
      parasite antigen into the footpad of syngenic normal recipients produced a
      dramatic enhancement in the DTH response, except at the onset of the DTH-negative
      phase. These observations indicate that adherent cells have a role in suppression
      of the cell-mediated immune response and also that another mechanism operates at
      the onset of the DTH-negative phase. This DTH-negative phase was not caused by
      depletion of DTH-mediating cells from the repertoire, but rather by suppression
      mediated by a subset of T cell evolved in the course of infection.
      Characterization on the basis of lymphokine production of the T cells mediating
      the DTH response and of T cells mediating suppression of the DTH response showed
      them to be of Th1 and Th2 type, respectively. Studies also indicated that at the
      onset and the later stages of infection suppression was mediated by adherent
      cells, but at the onset of DTH-negative phase, in particular, suppression was
      mediated by Th2 cells. Furthermore, experiments also showed that adherent cells
      from infected mice gained another property, that of driving B cells, in a T cell
      dependent manner.

PMID- 1386312
TI  - A protective NOD islet-infiltrating CD8+ T cell clone, I.S. 2.15, has in vitro
      immunosuppressive properties.
AB  - Type 1, insulin-dependent diabetes mellitus (IDDM) appears to result from a T
      cell-dependent destruction of insulin-producing pancreatic beta cells. In non
      obese diabetic (NOD) mice and in other rodent models of human IDDM, final
      expression of disease may be controlled by protective, as well as, destructive T
      cell influences. Previously, a CD8+ T cell clone, I.S. 2.15, was isolated
      directly from islets of disease-resistant male NOD mice. Upon transfer to young
      NOD recipients, the non-cytolytic I.S. 21.5 T cell clone, confers in vivo
      protection from two forms of accelerated IDDM. The present study demonstrates
      that I.S. 2.15 T cells induce in vitro immunosuppression. The suppressive effects
      of I.S. 2.15 T cells are mediated through soluble factor(s) and are independent
      of T cell activation, cell contact, antigen specificity or the major
      histocompatibility complex (MHC). By polymerase chain reaction (PCR), I.S. 2.15 T
      cells contain mRNA species encoding for the potentially immunosuppressive
      cytokines, interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta).
      The T cell suppressive effects engendered by I.S. 2.15 T cells closely mimic
      those observed with TGF-beta. Moreover, I.S. 2.15-induced immunosuppression
      correlates with intracellular levels of TGF-beta mRNA. These results establish
      that immunoregulatory T cells are present within islets in IDDM-resistant NOD
      mice and may impact on final disease expression through the production of soluble
      mediator(s).

PMID- 1386315
TI  - Co-crosslinking Fc epsilon RII/CD23 and B cell surface immunoglobulin modulates B
      cell activation.
AB  - Previous studies have shown that a highly multivalent from of anti-IgD or anti
      IgM, prepared by conjugating the respective antibodies to dextran, causes
      extensive B cell proliferation with ng/ml concentrations of the anti
      immunoglobulin (Ig). A modification of this system has been exploited to
      investigate the effect of co-crosslinking the Fc epsilon RII and surface Ig by
      binding DNP to the dextran backbone (DNP-dextran) and employing a DNP-specific
      monoclonal IgE of either rat or mouse origin. Addition of anti-IgD-(H delta
      a/1)[DNP-dextran] or anti-IgM-[DNP-dextran] to purified, resting murine B cells
      resulted in B cell proliferation over a broad dose (0.03-30 micrograms/ml).
      Addition of DNP-specific rat or mouse IgE dramatically modulated the
      proliferative response. Proliferation in response to doses greater than 0.3
      microgram/ml H delta a/1-[DNP-dextran] was consistently reduced in a dose
      dependent manner in the presence of increasing amounts of IgE while proliferation
      to lower concentrations of H delta a/1-[DNP-dextran] was slightly enhanced or not
      influenced at all by the IgE anti-DNP. Interleukin-4 (IL-4) significantly
      increased the IgE effect, in line with its known enhancing effects on Fc epsilon
      RII levels. Experiments measuring Ig production rather than proliferation
      demonstrated that in the presence of IgE anti-DNP, B cells produced lower amounts
      of immunoglobulin (IgG1 or IgM) in response to an anti-Ig signal. Control
      experiments demonstrated that the IgE effect on proliferation was blocked by
      monoclonal anti-Fc epsilon RII, but not anti-Fc gamma RII, thus demonstrating the
      necessity for IgE/Fc epsilon RII interaction. In addition, the necessity for co
      crosslinking was shown by the inability of IgE anti-DNP to affect the
      proliferative response to H delta a/1-dextran even in the presence of various
      doses of DNP-dextran. These results demonstrate that co-crosslinking of sIg and
      the Fc epsilon RII results in an altered B cell response to anti-Ig mediated
      activation. IL-4 does not ablate this inhibition, in contrast to the effect of co
      crosslinking Fc gamma RII and surface Ig, suggesting a model whereby IgE can
      modulate its own production.

PMID- 1386314
TI  - Characterization of molecular components associated with surface immunoglobulin M
      in human B lymphocytes: presence of tyrosine and serine/threonine protein
      kinases.
AB  - To characterize the signal transduction through the antigen receptor (AgR) on
      human B lymphocytes, we analyzed its association with other molecular components.
      The surface IgM (sIgM) complex isolated in digitonin contains two surface
      expressed polypeptides--the previously described Ig alpha and Ig beta proteins-
      covalently linked to each other in a 48/39-kDa heterodimer. We show herein that
      the human sIgM complex isolated from the Burkitt's lymphoma cell line, Ramos, or
      from dense tonsillar B cells contains additional molecules--160 kDa and 75 kDa in
      size--and enzymatic activities able to phosphorylate on tyrosine as well as
      serine/threonine residues the 39-, 48-, 75- and 160-kDa polypeptides. By specific
      immunoprecipitation with antibodies to src-family kinases, we consistently
      detected p56lyn in the sIgM complex. In the Ramos cell line, both p56lck and
      p59fyn activity were also observed, although to a much lesser extent than p56lyn.
      These kinases are associated with sIgM before cell stimulation. As shown by two
      dimensional electrophoresis, they interact in a tight complex with multimeric
      forms of the Ig alpha and Ig beta components. The kinases are active in vitro but
      must be highly regulated in vivo: Western blotting with anti-phosphotyrosine
      antibodies revealed that stimulation of the AgR on viable B cells increased
      detectable phosphotyrosine residues on the components present in the sIgM
      complex. Based on these phosphorylation changes, the 39-, 48-, 75- and 160-kDa
      molecules are likely to be functionally active elements in an IgM complex crucial
      for the transduction of the antigenic signal.

PMID- 1386316
TI  - Attenuation of autoimmune disease and lymphocyte accumulation in MRL/lpr mice by
      treatment with anti-V beta 8 antibodies.
AB  - MRL-MP-lpr/lpr mice are afflicted by a severe systemic autoimmune disease that is
      aggravated by the lpr mutation resulting in the accumulation of phenotypically
      abnormal lpr cells (CD3+CD4-CD8-) in all lymphoid issues including hyperplastic
      lymph nodes. Given that products of the T cell receptor V beta 8 gene family are
      overrepresented among lpr cells, different schedules aimed at selectively
      decreasing the frequency of lpr cells were designed. First, continuous
      administration of the monoclonal antibody F23.1 (specific for V beta 8 products)
      resulted in a significant depletion of V beta 8+ cells and prevented the
      manifestation of lymph accumulation at the same time as it reduced the
      serological, clinical, and histopathological signs of autoimmune disease. Along
      the same line, administration of either F23.1 or two different anti-F23.1 anti
      idiotypic antibodies to MRL/Mp-lpr/lpr mothers elicited, in the offspring, the
      production of antibodies sharing a recurrent idiotype with F23.1 and resulted in
      long-term amelioration of autoimmunity and lymphadenopathy. Thus, a strategy
      aimed at specifically reducing the frequency of a subset of lpr cells proved
      successful in mitigating the autoimmune process.

PMID- 1386317
TI  - Presence of murine fetal liver cells capable of being induced to differentiate in
      vitro into T cell receptor-positive cells.
AB  - Mouse fetal liver cells were analyzed for the surface expression of T cell
      markers. Fetal liver cells prepared from mouse embryos at 14.5 days of gestation
      contained a small number of CD4+ cells (1.4%), but virtually no cells positive
      for any other T cell markers such as CD8, CD3 and T cell receptor (TcR). When a
      fetal liver cell suspension prepared from BALB/c(male) x AKR(female) F1 embryos
      at 14.5 days of gestation was cultured in medium supplemented with culture
      supernatants of both WEHI-3 and concanavalin A-stimulated rat spleen cells, TcR
      alpha beta+ and CD4+ cells were generated, whereas CD8+ and TcR gamma delta+
      cells were hardly detectable. Most of TcR alpha beta+ and CD4+ cells were H-2d+,
      thus clearly showing their fetal origin. Treatment with anti-CD4, anti-CD3 or
      anti-TcR alpha beta antibodies plus complement or electronic sorting to remove
      cells expressing these markers failed to inhibit the generation of T cell marker
      positive cells following culture in vitro. On the other hand, depletion of Thy
      1.2+ cells reduced their generation. These findings indicate the presence of some
      progenitor T cells in fetal liver with the Thy-1+, CD3-, CD4-, CD8-, TcR-
      phenotype, which can be induced to differentiate into TcR alpha beta+ cells in
      the presence of specific humoral supplements without the influence of the thymus.

PMID- 1386319
TI  - Commitment to the T cell receptor-alpha beta or -gamma delta lineages can occur
      just prior to the onset of CD4 and CD8 expression among immature thymocytes.
AB  - Two types of T lymphocytes, distinguishable by their surface expression of either
      the gamma delta or the alpha beta T cell receptor (TcR) for antigen, populate the
      periphery in the adult. In addition, immature precursors of both T cell types can
      be found in the thymus. While it is generally accepted that these two cell types
      represent distinct lineages, it is not known at which developmental stage these
      lineages diverge. The most mature thymocyte precursor population not yet
      expressing T lineage-specific surface markers (i.e. CD3, CD4, and CD8) is known
      to be capable of generating TcR-alpha beta T cells, and has been thought to be
      preprogrammed into the TcR-alpha beta lineage at an earlier developmental stage.
      We now show that this late-stage precursor is capable of giving rise to cells of
      both the TcR-alpha beta and -gamma delta lineages, both in vitro after
      intrathymic transplantation, and in vitro in simple culture medium or medium with
      cytokines. Thus it appears that the divergence of TcR-alpha beta and -gamma delta
      cells can occur at a relatively late stage of intrathymic development, just prior
      to the onset of CD4 and CD8 expression in most cells.

PMID- 1386318
TI  - Differential effect of transforming growth factor beta on the synthesis of Th1-
      and Th2-like lymphokines by human T lymphocytes.
AB  - (TGF)-beta is a pluripotent cytokine exerting differential effects on distinct
      components of the immune response. The present report, based on lymphokine
      determination in culture supernatants and Northern blot analysis of lymphokine
      mRNA, demonstrates that TGF-beta 2 markedly inhibits interleukin (IL)-4 and IL-5
      synthesis by polyclonally activated human T cells in the absence of any
      significant effect on (IFN)-gamma, lymphotoxin or IL-2, suggesting a modulatory
      effect of TGF-beta 2 on the interferon Th1/Th2) balance of immune responses. The
      inhibitory effect of TGF-beta on IFN-gamma production by unfractionated
      peripheral blood mononuclear cells is likely to reflect the blunting of natural
      killer cell activation by TGF-beta.

PMID- 1386320
TI  - pH dependency of the binding of [3H]BAY U 3405 and various non-labelled ligands
      to the thromboxane A2/prostaglandin H2 receptor of human platelet membranes.
AB  - [3H]BAY U 3405 was used to characterize the effect of acidic and alkaline pH
      values on the binding of the thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor
      of human platelet membranes. The specific binding of [3H]BAY U 3405 largely
      increased upon acidification up to pH 5.8. Saturation binding studies revealed an
      increase in binding affinity without change in the number of binding sites. At pH
      7.4 the Kd was 8.7 +/- 3.7 nM (Bmax = 6.6 +/- 0.6 pmol/mg protein) compared to
      1.2 +/- 0.2 nM (Bmax = 6.1 +/- 0.6 pmol/mg protein) at pH 5.8. A more than 10
      fold higher rate of association was observed at pH 5.8 compared to pH 7.4, while
      the rate of dissociation showed only minor changes. The kinetically derived
      dissociation constant was 1 nM (pH 5.8) and 9.6 nM (pH 7.4). The pH dependency of
      the binding of structurally different non-labelled ligands to the TXA2/PGH2
      receptor was evaluated by inhibition studies at pH 5.8 and pH 7.4. BAY U 3405,
      daltroban, CTA2, and U 46619 showed significantly higher affinities at pH 5.8. In
      contrast, I-PTA-OH and GR 32191 had a higher affinity at pH 7.4. No significant
      difference was seen with SQ 29548 at the observed pH values. A second protonable
      group within the molecules I-PTA-OH, GR 32191, and SQ 29548 might be responsible
      for the observed differences.

PMID- 1386321
TI  - Evidence for pulsatile secretion of human atrial natriuretic peptide in healthy
      subjects.
AB  - The secretion pattern of human atrial natriuretic peptide (hANP) was investigated
      in 8 healthy male volunteers. Blood was drawn in 2 minute intervals for 90
      minutes and in a second study in 4 minute intervals for 180 minutes. Base-line
      hANP plasma levels varied in a pulsatile secretion pattern of regular pulses
      every 9 +/- 1 minutes. Additionally long-term oscillations of 34 +/- 4 minutes
      were found. These data suggest that under basal conditions hANP varies in a
      pulsatile fashion.

PMID- 1386322
TI  - Dehydroepiandrosterone (DHEA) levels in patients with prostatic cancer, heart
      diseases and under surgery stress.
AB  - DHEA levels in patients with prostatic cancer were significantly lower, but total
      and free testosterone (T) significantly higher as those in an age-matched control
      group. Therefore, the calculated quotients DHEA/free T and DHEA/T were especially
      different between both groups. DHEA and DHEAS levels in patients with heart
      diseases were also significantly lower but cortisol (F) levels were significantly
      higher as those in a control group. The quotients DHEA/F and DHEAS/F were also of
      greater significance between both groups than the hormone values alone. The
      response of DHEA and F levels in patients undergoing surgery showed an increase
      of both steroids under surgery. On the second postoperative day, however, F
      levels were still significantly higher but DHEA levels were significantly lower
      as the initial values. The differences between the initial values and those on
      the second postoperative day of F and DHEA showed a significant correlation, i.e.
      the higher the elevation of F levels above the initial values the greater was the
      diminution of DHEA levels below the initial values.

PMID- 1386323
TI  - Differential increase in activity of acid phosphatase induced by phosphate
      starvation in Tetrahymena.
AB  - We have studied the effects of phosphate starvation on the levels and
      distributions of activities of acid phosphatase and beta-hexosaminidase in
      cultures of Tetrahymena thermophila. The cells were grown in synthetic nutrient
      medium and refed every day with fresh medium. After 4 days of growth in the
      complete medium, the cultures were divided into two portions. One received
      complete medium and the other phosphate-free, but otherwise complete, medium.
      Population densities and activities of acid phosphatase and beta-hexosaminidase
      in cells plus medium and in cell-free samples were determined in aliquots removed
      every day before medium replacement. In cultures having complete medium the
      enzyme levels remained fairly constant; in the phosphate-starved cultures both
      total and extracellular activities of acid phosphatase increased sixfold. beta
      Hexosaminidase levels remained essentially unaltered in both cases. These results
      indicate that phosphate starvation can induce differential increase in acid
      phosphatase activity in cultures of Tetrahymena. Somewhat less than 50% of the
      total activities of both enzymes are found in the cell-free extracellular fluid
      at any time.

PMID- 1386324
TI  - Inhibition of mouse lymphocyte proliferative response by glycosphingolipids from
      Leishmania (L.) amazonensis.
AB  - The effect of a purified preparation of glycosphingolipids (GSLs) extracted from
      Leishmania (L.) amazonensis amastigotes on murine lymphocytes was investigated.
      GSLs inhibited both concanavalin A (Con A)- or lipopolysaccharide-induced
      [3H]thymidine uptake by normal and immunized BALB/c mouse lymph node cells. The
      effect of total GSLs was dose dependent. Total GSLs also suppressed the two-way
      mixed lymphocyte reaction of BALB/c x C57BL/6 cells and the antigen-specific
      response of immunized mouse cells. Six pure bands as well as a pool containing a
      mixture of GSLs with five to seven sugar residues separated by a combination of
      HPLC and preparative HPTLC were tested and shown to be inhibitors of Con A
      stimulation. These results suggest that parasite glycosphingolipids may play an
      immunologically relevant role in leishmaniasis.

PMID- 1386325
TI  - The cellular immune response to heat shock proteins.
AB  - T lymphocytes, which are central to almost every immune response, frequently
      recognize microbial hsp60. Such cells could provide an early defense mechanism
      against pathogenic microbes. However, T cells also recognize epitopes of hsp60
      shared by microbe and host. Not only conventional alpha/beta T cells respond to
      hsp60; gamma/delta T cells do so, as well. In fact, certain gamma/delta T cells
      seem to have a particular preference for this molecule. Recognition of stressed
      host cells expressing hsp60 could facilitate the scavenger function of the T cell
      system. On the other hand, such recognition could be involved in autoimmune
      disease.

PMID- 1386326
TI  - Effects of hypertension and hyperlipidemia on the myocardium and coronary
      vasculature of the WHHL rabbit.
AB  - This study was undertaken to study the effects of hyperlipidemia and hypertension
      on the coronary circulation and on the myocardium of Watanabe heritable
      hyperlipidemic (WHHL) rabbits. Surgery to induce hypertension by the one-kidney,
      one-clip technique was performed on the WHHL rabbits at 3 months of age. At 3 and
      6 months after surgery, the right and left coronary arteries and the left
      ventricle and posterior papillary muscle from normotensive and hypertensive
      animals were assessed. Atherosclerotic involvement was found at the coronary
      origin in 94% of the arteries evaluated. Lesions were usually confined to the
      proximal 1-2 mm of the coronary artery. The prevalence of coronary
      atherosclerosis in the WHHL rabbit was found to be higher than previously
      reported in rabbits of the same age. Hypertension-induced muscular and vascular
      changes such as left ventricular hypertrophy, medial thickening of the arteries,
      and hyaline arteriolosclerosis were found in most of the hypertensive animals.
      These changes were rarely seen in the normotensive rabbits. Characteristics of
      ischemia and cell injury such as eosinophilic fibers, fiber vacuolization, and
      contraction band necrosis were found more often in hypertensive than in
      normotensive WHHL rabbits. Confluent areas of severe necrosis indicative of
      myocardial infarction were not found; myocardial damage was diffuse and involved
      individual cells and small microscopic areas. This model may be valuable in
      further studies of coronary artery disease and myocardial injury that result from
      the combination of hypercholesterolemia and hypertension.

PMID- 1386327
TI  - Meta-analysis of efficacy of zinc acexamate in peptic ulcer.
AB  - Zinc acexamate (ZAC) is a new drug for the treatment of peptic ulcer. The present
      study was performed in order to evaluate the clinical efficacy of ZAC in peptic
      ulcer, using a meta-analysis of all randomized clinical trials performed with
      this drug. Eighteen studies were reviewed, but only 13 were considered in the
      final analysis. The total number of patients was 757. Control groups included
      placebo or H2 receptor antagonist drugs. Healing rate, assessed by endoscopy, was
      selected as the criterion for evaluating drug efficacy. The meta-analysis was
      performed using a modified version of the Mantel-Haenszel method. ZAC proved to
      be better than placebo in the treatment of peptic ulcer (pooled odds ratio: POR =
      5.55; 95% confidence interval: 95% CI = 2.20-14.04) and not different from H2
      receptor antagonist drugs when compared in patients with gastric (POR = 1.14; 95%
      CI = 0.47-2.72), duodenal (POR = 0.97; 95% CI = 0.13-7.33) or both ulcer types
      (POR = 1.10; 95% CI = 0.74-1.64). The present results show that ZAC is an
      effective drug for the treatment of peptic ulcer.

PMID- 1386329
TI  - [Prevalence of hereditary pathologies in residents of the Kirov Province].
AB  - Medical-genetic study was carried out in the population of Kirov Province
      (population size about 120.000). 203 families with 334 affected with hereditary
      disorders were registered. The correctness of pathology classification for the
      inheritance type was confirmed by segregational analysis. The load of hereditary
      diseases in the population was: 1.25 +/- 0.06 for autosomal dominant, 1.37 +/-
      0.07 for autosomal recessive and 0.22 +/- 0.06 for X-linked recessive disorders.
      It is suggested that variability in the values of the load of autosomal recessive
      disorders is determined to the large extent by genetic structure of the
      population.

PMID- 1386328
TI  - Presence and properties of acyl coenzyme A synthetase for medium-chain fatty
      acids in rat intestinal mucosa.
AB  - A system was developed for assay of acyl coenzyme A (acyl CoA) activity on medium
      chain fatty acids in rat intestinal mucosa. Using this system, we compared the
      characteristics of octanoyl (C8:0) CoA synthetase activity and palmitoyl (C16:0)
      CoA synthetase activity. Palmitoyl CoA synthetase activity as a function of
      palmitate concentration followed Michaelis-Menten kinetics, but octanoyl CoA
      synthetase activity as a function of octanoate concentration showed a biphasic
      reaction curve. The distributions of octanoyl CoA synthetase activity and
      palmitoyl CoA synthetase activity along the gastrointestinal tract were similar,
      both activities being present mainly in the middle portion of the small
      intestine. Incubation of octanoate with a homogenate of intestinal mucosa
      revealed that octnoate, like palmitate, is incorporated into phospholipids and
      triglycerides after its CoA activation. Oral administration of medium chain
      triglycerides induced a nearly 2-fold increase in octanoyl CoA synthetase
      activity in rat intestinal mucosa, whereas oral administration of long chain
      triglycerides did not affect the palmitoyl CoA synthetase activity. These results
      indicate that acyl CoA synthetase for medium-chain fatty acids in rat intestinal
      mucosa plays a key role in the utilization of medium-chain fatty acids for lipid
      synthesis, and that it is regulated in a different manner from acyl CoA
      synthetase for long-chain fatty acids.

PMID- 1386330
TI  - [Cloning and complementation analysis of the Escherichia coli gpr locus,
      influencing DNA replication of certain lamdoid phages].
AB  - Escherichia coli DNA fragments which suppressed gpr27 and gpr2 mutations in the
      earlier proposed gprA and gprB genes, respectively, were cloned within phage
      vectors. Mutations gpr2 and gpr27 restrict DNA replication of some lambdoid
      phages and are located in the region of dnaK, J genes. DNA-DNA hybridization
      showed that the cloned fragments correspond to the region where gpr mutations
      were genetically mapped and, in some cases, do not include dnaK, J genes. These
      results provide the evidence that gprA and gprB genes may be physically separated
      from dnaK, J genes.

PMID- 1386331
TI  - A broad bean cDNA clone encoding a DNA-binding protein resembling mammalian CREB
      in its sequence specificity and DNA methylation sensitivity.
AB  - A plant cDNA has been cloned that encodes a DNA-binding protein displaying a
      nucleotide (nt) sequence specificity similar to that of the mammalian cyclic AMP
      response element-binding protein/activating transcription factor (CREB/ATF)
      family of mammalian proteins. This cDNA was cloned in Escherichia coli from a
      broad bean (Vicia faba) cDNA expression library using a recognition site probe.
      The deduced amino acid (aa) sequence of the recombinant cDNA-encoded protein,
      called VBP1, has a basic region adjacent to a leucine zipper motif, of the type
      seen in the DNA-binding domains of many eukaryotic DNA-binding proteins,
      including mammalian CREB/ATF. Although this aa sequence has homology to regions
      of deduced aa sequences of other cloned plant cDNAs, it is distinct in both the
      derived primary structure and in its nt sequence specificity. VBP1, as well as
      proteins in nuclear extracts of V. faba with similar nt sequence specificity,
      have their binding to DNA suppressed more than tenfold by cytosine methylation at
      the CREB/ATF consensus sequence.

PMID- 1386332
TI  - Genomic structure of the putative BTF3 transcription factor.
AB  - On the basis of the amino acid (aa) sequence of the putative BTF3 transcription
      factor, two complementary DNAs coding for the two proteins, BTF3a and BTF3b, have
      been cloned from a HeLa cell cDNA library. The two proteins are identical, except
      that BTF3b lacks the first 44 N-terminal aa present in BTF3a. These proteins
      originate from the same gene, which contains seven exons, and are the products of
      alternative splicing. The promoter region, containing a putative TATA box(es) and
      a CAAT box sequence, was identified. In addition, three other BTF3-like genes
      were characterized.

PMID- 1386333
TI  - The hemodynamic status of preascitic cirrhosis: an evaluation under steady-state
      conditions and after postural change.
AB  - To assess the hemodynamic status of patients with compensated cirrhosis, mean
      arterial pressure, cardiac index and peripheral vascular resistance and markers
      of central (plasma concentrations of atrial natriuretic factor) and arterial
      volemia (plasma norepinephrine concentration, plasma renin activity) were studied
      in 10 patients and 10 healthy control subjects under steady-state conditions
      (after 2 hr of standing) and after assumption of the supine position (30, 60, and
      120 min). After standing, neither hemodynamics nor markers of effective volemia
      differed significantly between controls and patients. By evaluating the areas
      under the curve during the 2 hr of supine posture, the increase in cardiac output
      and plasma natriuretic factor and the decrease in peripheral vascular resistance
      were greater in patients (2.59 +/- 0.43 [S.E.M.] L/min/hr; 32.8 +/- 7.2 pg/ml/hr 
      1,103 +/- 248.4 dyn.sec/cm5/hr, respectively) than in controls (0.53 +/- 0.24
      L/min/hr, p = 0.005; 17.4 +/- 4.7 pg/ml/hr, p = 0.005; -265.5 +/- 206.2
      dyn.sec/cm5/hr, p = 0.02). The declines in heart rate, plasma norepinephrine
      concentration and plasma renin activity did not differ significantly. Mean
      arterial pressure did not significantly change. Our results suggest that during
      periods of upright posture, cirrhotic patients in the preascitic stage, who are
      known to have expanded blood volume, compensate for dilatation of the splanchnic
      vascular bed through total hypervolemia. The latter becomes excessive during
      recumbency, leading to supernormal increases in venous return, central volemia
      and cardiac index. The decline in peripheral vascular resistance appears to be a
      compensatory mechanism to maintain steady arterial blood pressure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1386334
TI  - Small cell colonies appear in the primary culture of adult rat hepatocytes in the
      presence of nicotinamide and epidermal growth factor.
AB  - Colonies of small hepatocytes appeared after the culture of primary adult rat
      hepatocytes for 4 days in serum-free modified Dulbecco's modified Eagle's medium
      containing 10 mmol/L nicotinamide and 10 ng/ml epidermal growth factor. Each
      colony consisted of cells that had a single nucleus and a higher
      nucleus/cytoplasm ratio than surrounding hepatocytes, and immunocytochemically
      these cells were stained with albumin and transferrin. Ultrastructurally these
      cells had mitochondria, peroxisomes and desmosomes, indicating that they were
      derived from hepatocytes. When 6 x 10(5) cells were plated on 35-mm dishes, about
      5.5 colonies/mm2 were observed. This result suggested that about 1.5% of adult
      rat hepatocytes has the potential for multiple replications and of forming a
      focal colony. These cell populations had higher proliferative activities than
      surrounding hepatocytes. DNA synthetic activity could not be inhibited by 2%
      dimethyl sulfoxide. Flow cytometric analysis showed that both 2N and 4N nuclei
      synthesized their DNA until day 4 but that the number of 2N nuclei rapidly
      increased at day 5. This result correlated with the observation of the appearance
      of small cell populations indicating that the cells of these focal colonies were
      predominantly diploid.

PMID- 1386335
TI  - Genomic organization, chromosomal localization, and independent expression of
      human cyclin D genes.
AB  - Murine cDNA clones for three cyclin D genes that are normally expressed during
      the G1 phase of the cell cycle were used to clone the cognate human genes.
      Bacteriophage and cosmid clones encompassing five independent genomic loci were
      partially sequenced and chromosomally assigned by an analysis of somatic cell
      hybrids containing different human chromosomes and by fluorescence in situ
      hybridization to metaphase spreads from normal peripheral blood lymphocytes. The
      human cyclin D1 gene (approved gene symbol, CCND1) was assigned to chromosome
      band 11q13, cyclin D2 (CCND2) to chromosome band 12p13, and cyclin D3 (CCND3) to
      chromosome band 6p21. Pseudogenes containing sequences related to cyclin D2 and
      cyclin D3 mapped to chromosome bands 11q13 and 6p21, respectively. Partial
      nucleotide sequence analysis of exons within each gene revealed that the
      authentic human cyclin D genes are more related to their mouse counterparts than
      to each other. These genes are ubiquitously transcribed in human tumor cell lines
      derived from different cell lineages, but are independently and, in many cases,
      redundantly expressed. The complex patterns of expression of individual cyclin D
      genes and their evolutionary conservation across species suggest that each family
      member may play a distinct role in cell cycle progression.

PMID- 1386336
TI  - Molecular cloning and chromosomal mapping of CCND genes encoding human D-type
      cyclins.
AB  - A human D-type cyclin gene (CCND1/cyclin D1/PRAD1) was previously isolated by
      virtue of its ability to complement a triple G1 cyclin (Cln) deficiency of
      Saccharomyces cerevisiae and was also identified as a candidate BCL1 oncogene. We
      now report the molecular cloning of two additional human D-type cyclin genes,
      CCND2 (cyclin D2) and CCND3 (cyclin D3). All three human D-type cyclin genes
      encode small (33-34 kDa) proteins that share an average of 57% identity over the
      entire coding region and 78% in the cyclin box. The D-type cyclins are most
      closely related to cyclin A (39% identity) and cyclin E (36%), followed by cyclin
      B (29%) and cyclin C (21%). Isolation and characterization of genomic clones
      revealed two pseudogenes corresponding to CCND2 and CCND3, respectively. All
      three cyclin D genes are interrupted by an intron at the same position. CCND2 has
      been mapped to chromosome 12p13, and CCND3 has been mapped to chromosome 6p21.

PMID- 1386337
TI  - The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in
      the region of the IL-1 alpha and IL-1 beta loci.
AB  - The IL-1 receptor antagonist (IL-1RN) is a protein that binds to IL-1 receptors
      and inhibits the binding of IL-1 alpha and IL-1 beta. As a consequence, the
      biological activity of these two cytokines is neutralized in physiological and
      pathophysiological immune and inflammatory responses. In this study, using a
      panel of somatic rodent-human cell hybrids, we show that the gene for the human
      interleukin-1 receptor antagonist (IL1RN) maps to the long arm of chromosome 2.
      Previously, we described a length variation polymorphism within the second intron
      of the IL-1RN gene (Steinkasserer et al., 1991, Nucleic Acids Res. 19: 5095).
      Segregation of this, together with an IL-1 alpha polymorphism, was followed in a
      panel of five CEPH families. Linkage analysis permitted the mapping of the IL-1RN
      gene to band q14-q21 in the region for the IL-1 alpha and IL-1 beta loci. This
      study supports the view that an early gene duplication event resulted in the
      creation of an interleukin-1 gene family.

PMID- 1386338
TI  - Genomic sequence and chromosomal location of human interleukin-11 gene (IL11).
AB  - The genomic sequence of human interleukin-11 (IL11) has been isolated based on
      its sequence homology with a cDNA clone encoding primate IL11. The human IL11
      genomic sequence is 7 kb in length and consists of five exons and four introns.
      The IL11 gene has been localized to the long arm of human chromosome 19 at band
      19q13.3-q13.4 by in situ hybridization. Several potential transcriptional control
      sequences that may play an important role in the control of IL11 gene expression
      have been identified within the 5'-flanking region of the human IL11 gene. The 5'
      flanking region of the human IL11 gene contains sequences similar to those
      present in the 5'-regulatory regions of other cytokine genes. Four repeats of a
      30-bp DNA segment were found in the fourth intron, and several copies of ATTTA
      and Alu repetitive sequences were identified in the 3'-noncoding region of the
      human IL11 gene. A DNA sequence (ACATGGCAAAACCC) that has 71% similarity with the
      IL1-responsive element of the IL6 gene was found in the 3'-flanking region of the
      human IL11 gene. The two polyadenylation sites located at nucleotide positions
      6762 and 5591 correspond to the 2.5- and 1.5-kb IL11 transcripts expressed in IL1
      induced PU-34 cells. The availability of the human IL11 genomic sequence should
      aid in studies of the regulatory mechanisms of IL11 gene expression in different
      cell types and the role of IL11 expression in the hematopoietic microenvironment.

PMID- 1386339
TI  - Identification of a CA repeat at the TCRA locus using yeast artificial
      chromosomes: a general method for generating highly polymorphic markers at chosen
      loci.
AB  - The creation of a comprehensive genetic map in human has been limited by the lack
      of highly polymorphic markers spaced evenly throughout the human genome. We have
      utilized yeast artificial chromosomes (YAC) containing large human DNA inserts to
      help identify highly polymorphic (CA)n repeats at a chosen locus. The DNA of a
      YAC containing the locus was subcloned in M13 vectors, and the recombinants were
      screened at high stringency to detect preferentially long (CA)n repeats (n
      greater than 20). These repeats, which are the most likely to be highly
      polymorphic, were then studied to confirm both the level of polymorphism and
      their precise genetic location. This strategy has permitted the identification of
      a new, highly polymorphic CA repeat (77% heterozygosity) at the T cell receptor
      alpha chain (TCRA) locus on chromosome 14q. It provides a powerful marker for
      assessing the role of this locus in the susceptibility to autoimmune and
      infectious diseases. This approach should permit the development of highly
      polymorphic markers at any targeted locus and rapidly improve the current human
      genetic map.

PMID- 1386340
TI  - Localization of the gene coding for ventricular myosin regulatory light chain
      (MYL2) to human chromosome 12q23-q24.3.
AB  - Human myosin light chain-2 (MYL2) is an important protein involved in the
      regulation of myosin ATPase activity in smooth muscle. In cardiac muscle, the
      precise role of MYL2 is not well understood; however, an increase in ventricular
      MYL2 is observed during myocardial hypertrophy in cardiac patients with valve
      stenosis. The chromosomal location of the gene coding for MYL2 was identified
      using a cloned cDNA for human MYL2. Southern blot analysis of DNA from a
      human/rodent somatic cell hybrid mapping panel showed that the BamHI fragment
      that hybridized with this cDNA probe was concordant with chromosome 12. The 768
      bp cDNA was hybridized to human metaphase chromosomes. The results revealed a
      significant clustering of silver grains over chromosome 12 bands q23-q24.3,
      indicating that the gene coding for MYL2 is located in this region.

PMID- 1386342
TI  - Assignment of two human cell cycle genes, CDC25C and CCNB1, to 5q31 and 5q12,
      respectively.

PMID- 1386341
TI  - cDNA sequence of human p11 calpactin I light chain.
AB  - The cDNA encoding full-length human p11 calpactin I light chain has been cloned
      and subjected to DNA sequencing. The open reading frame specifies a 97-amino-acid
      residue protein that surprisingly is identical to the p11 sequences of two
      mammalian ungulate species, cow and pig. However, the previously reported p11
      polypeptide sequences of mouse and rat exhibited 8-9% nonidentity to human p11.
      These mammalian sequence comparison results are unexpected in view of current
      molecular cladistic theories that suggest a closer relationship between primates
      and rodents, rather than primates and ungulates. The mouse p11 gene has been
      previously mapped to chromosome 3 at a position syntenic with a centromeric
      proximal region on human chromosome 1, and the human p11 cDNA clone is likely to
      be useful in physical mapping on chromosome 1.

PMID- 1386343
TI  - Regional mapping of the human hepatocyte growth factor (HGF)-scatter factor gene
      to chromosome 7q21.1.

PMID- 1386344
TI  - Down-regulation of E1a expression by E3 gene products in group C adenoviruses.
AB  - Mutant group C adenoviruses defective in expression of the E3 transcription unit
      were found to overexpress E1a proteins relative to wild-type adenoviruses. This
      result suggests that one or more proteins encoded in the E3 region (present in
      wild-type viruses) down-regulate E1a expression. This interpretation was
      confirmed by transfection experiments in which a plasmid expressing the E3 region
      reduced expression of E1a in 293 cells. Experiments to examine the molecular
      basis of this down-regulation of E1a suggest that E3 protein products interfere
      with the translation of viral mRNA molecules.

PMID- 1386346
TI  - Salt supplementation does not alter the pressor effect of blocking atrial
      natriuretic peptide in nucleus tractus solitarii.
AB  - We have previously shown that microinjection of monoclonal antibody to atrial
      natriuretic peptide (ANP) into the caudal nucleus tractus solitarii causes a
      pressor response in salt-sensitive spontaneously hypertensive rats (SHR) fed a
      basal (1%) salt diet, suggesting that endogenous ANP in this region may be
      involved in the centrally mediated regulation of blood pressure in this model.
      The present study tested the hypothesis that the pressor effect of blocking
      endogenous ANP in caudal nucleus tractus solitarii is enhanced by dietary salt
      supplementation in salt-sensitive SHR. Monoclonal antibody to ANP (0.55
      micrograms) in 50 nl artificial cerebrospinal fluid or control immunoglobulin G
      was microinjected into the caudal nucleus tractus solitarii of conscious salt
      sensitive SHR, salt-resistant SHR, and Wistar-Kyoto rats fed 1% or 8% salt diets
      for 3 weeks. Microinjection of the monoclonal antibody into the caudal nucleus
      tractus solitarii evoked similar increases in mean arterial pressure in salt
      sensitive SHR on both 1% and 8% salt diets and in salt-resistant SHR on a 1% salt
      diet but had no effect in Wistar-Kyoto rats. In contrast, microinjection of
      control immunoglobulin G into this brain area did not alter mean arterial
      pressure or heart rate in any experimental group. Thus, endogenous ANP in caudal
      nucleus tractus solitarii mediates tonic control of blood pressure in both salt
      sensitive and salt-resistant SHR but not in Wistar-Kyoto rats, and this effect is
      independent of the salt sensitivity of hypertension and of dietary salt intake.

PMID- 1386345
TI  - Somatic cell mapping of T-cell receptor CD3 complex and CD8 genes in cattle.
AB  - Bovine genes encoding T-cell receptor, CD3, and CD8 molecules have been mapped to
      syntenic groups using bovine x rodent hybrid somatic cells. T-cell receptor alpha
      and delta chains were assigned to bovine syntenic group U5, and the beta and
      gamma genes were syntenic with each other and with markers on U13. CD3E and CD3D
      genes were syntenic with each other and located to bovine syntenic group U19. CD8
      was most concordant with markers of syntenic group U16, although the concordancy
      was only 85% and the assignment must be regarded as tentative. The comparative
      gene maps of human chromosome 7, bovine syntenic group U13, and mouse chromosomes
      6 and 13 suggest extensive evolutionary conservation.

PMID- 1386347
TI  - Cell extracts of Candida albicans block adherence of the organisms to endothelial
      cells.
AB  - Cell extracts of Candida albicans were fractionated by concanavalin A affinity
      chromatography. Eluted mannosylated proteins (fraction II) and nonbinding,
      nonmannosylated proteins (fraction I) were collected and assayed directly for
      inhibition of adherence of C. albicans to endothelium. Fraction II blocked
      blastospore adherence to endothelial cells. Fraction I blocked both blastospore
      and germ tube adherence to endothelial cells. Monoclonal antibody OKM-1 (anti
      CR3) and an anti-C. albicans monoclonal antibody, CA-A (anti-CR2), reacted in
      Western blots with proteins from fraction I, suggesting the presence of the CR2-
      and CR3-like proteins that have been previously identified on C. albicans germ
      tubes.

PMID- 1386348
TI  - MHC class-I-restricted auto-tumor-specific CD4+CD8- T-cell clones established
      from autologous mixed lymphocyte-tumor-cell culture (MLTC).
AB  - Autologous mixed lymphocyte-tumor cell cultures (MLTC) were initiated with
      cytokine (IFN gamma and TNF alpha)-treated ex-vivo tumor cells of lung, ovarian,
      breast and stomach carcinomas. The cytokine-treated tumors expressed class-I but
      not class-II molecules. Although the proportion of CD8+ lymphocytes increased in
      the bulk culture of MLTCs, in 5/7 experiments the majority of the established T
      cell clones were CD4+. Among the CD8+ clones a high proportion (77%) was
      cytotoxic, while the proliferative response was more frequent among the CD4+
      clones (70%). In 4/26 cytotoxic T-lymphocyte (CTL) clones (3/17 CD4+ and 1/9
      CD8+), derived from a patient with class I+ class II- stomach carcinoma, lysis
      was restricted to the autologous tumor cells. These auto-tumor-specific clones
      did not lyse the autologous ConA blasts, the 5 allogeneic ex-vivo tumors, the NK
      sensitive K562 or the relatively sensitive Daudi cells. The cytotoxicity of these
      clones was inhibited by pre-incubation of the tumor cells with W6/32 (alpha-class
      I) MAb, or by preincubation of the lymphocytes with OKT3 (alpha-CD3) MAb. The
      alpha-CD4 (OKT4) MAb had only a marginal effect on the CD4+ clones, while the
      lytic function of the CD8+ clone was inhibited by the alpha-CD8 (OKT8) MAb. The 3
      CD4+ CTL clones also responded with proliferation to the autologous tumor cells.
      This proliferative response was inhibited by the presence of W6/32 MAb. Our
      results indicate that the auto-tumor lysis exerted by CD4+ CTL clones was
      restricted by the class-I antigens, and that the CD4 molecules of the clones were
      not essential for the lytic interaction.

PMID- 1386349
TI  - Optimization of culture conditions for activation and large-scale expansion of
      human T lymphocytes for bispecific antibody-directed cellular immunotherapy.
AB  - We investigated the optimal culture conditions (i.e., activation procedure,
      medium composition and type of culture vessel) for rapid in vitro expansion of
      large numbers (greater than 5 x 10(9) of blood T lymphocytes. These expanded
      lymphocytes can be targeted to be cytotoxic to ovarian carcinoma cells with a
      bispecific monoclonal antibody (BsAb) specific for CD3 and for the ovarian
      carcinoma-associated antigen MOv18. Both phytohemagglutinin (PHA) and monoclonal
      antibody (MAb) CD3 induced rapid T-cell proliferation, although the growth
      kinetics after PHA activation were slightly faster. A 50-fold increase in cell
      number was obtained after 14 and 16 days for PHA and CD3 MAb, respectively. The
      induction of BsAb-directed cytolysis was faster after CD3 MAb than after PHA
      activation of lymphocytes, but became similar around day 20. A mixture of media
      consisting of 78% RPMI 1640, 20% AIM-V and 2% human plasma (Mix-med) yielded
      better results than 100% AIM-V medium. Culture of lymphocytes in polyolefin bags,
      compared with tissue culture flasks, or cryopreservation did not affect
      lymphocyte yield and function. In most cultures the proportion of CD8+
      lymphocytes increased, suggesting a growth advantage of CD8+ over CD4+
      lymphocytes in this culture system. A protocol employing PHA activation, Mix-med
      and polyolefin bags has been used successfully to activate and expand blood
      lymphocytes for the first 5 patients entered into a phase-I/II clinical trial for
      the intraperitoneal treatment of ovarian carcinoma using CD3 x anti-MOv18 BsAb
      directed T lymphocytes.

PMID- 1386350
TI  - Plasma docosahexaenoic acid levels in various genetic forms of retinitis
      pigmentosa.
AB  - In 188 patients from separate families with various forms of retinitis pigmentosa
      (RP) and 91 normal subjects, plasma fatty acids were measured as a percentage of
      total plasma fatty acids, and their concentrations were determined using
      capillary-column gas-liquid chromatography. After controlling for the effects of
      age and gender, those with RP had significantly lower (P less than 0.01) mean
      plasma percentages and concentrations of the omega-3 fatty acids: 18:3 omega 3
      (alpha-linolenic acid), 22:3 omega 3 (13,16,19 docosatriaenoic acid), and 22:6
      omega 3 (docosahexaenoic acid, DHA) compared with the group of normal subjects.
      The mean percentages were reduced 15%, 14%, and 10%, respectively, below the mean
      percentages in normal subjects. Analysis by genetic type revealed that the X
      linked and isolate forms of RP had significantly lower (P less than 0.01) mean
      percentage values for DHA (18% and 17%, respectively). Dominant and recessive
      forms of RP had DHA levels close to normal. Mean absolute plasma DHA
      concentrations in X-linked RP were not significantly different from the
      concentrations in the control subjects, although these levels were significantly
      lower in patients with isolate RP. These data identify the possibility that some
      forms of RP may have alterations in plasma omega-3 fatty acid metabolism
      resulting in decreased plasma DHA content. These observations await additional
      confirmation using an analysis of the fatty acid content of specific erythrocyte
      phospholipid classes.

PMID- 1386351
TI  - Effect of steroids and nonsteroidal antiinflammatory agents on human ocular
      fibroblast.
AB  - 5-fluorouracil and steroids have been used to suppress excessive scar formation
      after glaucoma filtering surgery (GFS). Steroidal and nonsteroidal
      antiinflammatory drugs (NSAIDs), which are inhibitors of arachidonic acid (AA)
      pathway, both limit fibroblast activity and reduce inflammation. In this
      experiment, the ability of corticosteroid (dexamethasone sodium phosphate),
      cyclooxygenase inhibitor (piroxicam), lipoxygenase inhibitor (ferulic acid), and
      dual cyclo/lipoxygenase inhibitor (phenidone) to inhibit human Tenon's fibroblast
      proliferation was evaluated in culture. After human Tenon's fibroblast cell lines
      were established, a complete dose-response curve was done for the representative
      compounds for 8 days. Fibroblast attachment and proliferation were quantified by
      Coulter counter, hexosaminidase, and tritiated thymidine uptake assays. All four
      drugs inhibited attachment and proliferation at high concentrations. Phenidone
      was the most effective, with inhibition occurring within the 0.001-0.1 mmol/l
      range. It also was the only drug that showed inhibition at the antiinflammatory
      range in vivo. Dexamethasone, piroxicam, and ferulic acid did not inhibit
      fibroblast attachment and proliferation until doses well above those required to
      inhibit AA biosynthesis were attained. Only dexamethasone showed increased
      potency with incubation time. Overall, the NSAIDs showed antiproliferative
      activity comparable to or better than that of the steroids. Because the potency
      of steroids increases over time, these drugs may be more beneficial if given
      prior to initiation of inflammation. These results suggest that NSAIDs may be
      useful as both antiinflammatory and antiproliferative agents in preventing bleb
      failure after GFS.

PMID- 1386352
TI  - Frequency of HLA-DPB1 alleles, including a novel DPB1 sequence, in the Northern
      Ireland population.
AB  - HLA-DPB1 allele frequencies in 150 unrelated normal individuals from Northern
      Ireland were determined using oligonucleotide typing methods. HLA-DPB1*0401 was
      the most common allele in the population possessed by 75.3% of subjects, followed
      by DPB1*0201 (20.7%). In addition to these alleles, only HLA-DPB1*0402, 
      DPB1*0301, and -DPB1*0501 were present in subjects at frequencies greater than
      10%. The results in this study are in broad agreement with other Caucasoid
      studies, but there is regional and ethnic variation in HLA-DP allele frequencies.
      Three DPB1 alleles were found to be in linkage disequilibrium with HLA-DR
      antigens determined by RFLP, namely, DPB1*0101 with DRw17 (Dw24 associated) RFLP,
      DPB1*0501 with DRw13-Dw19 RFLP, and DPB1*1901 with DRw13-Dw18 (Dw25 associated)
      RFLP. One individual revealed a novel DPB1 pattern of probe reactivity, which
      following DNA sequencing was found to be HLA-DPB1*2001. To assess the system used
      and to compare consistency of results between laboratories, 62 cell lines were
      oligotyped for HLA-DP. The results revealed the system described here to be
      extremely accurate and showed excellent agreement of HLA-DP typing results for
      cell lines between laboratories.

PMID- 1386353
TI  - Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and
      humans.
AB  - The administration of murine mAb specific for the CD3 epsilon subunit of the TCR
      complex (OKT3) has been demonstrated to engender in humans an anti-OKT3 idiotypic
      cascade. This study used murine-derived anti-OKT3 (Ab2) as a bioreagent to
      determine whether this Ab2 and polyclonal anti-(anti-OKT3) (Ab3) generated in
      some human kidney transplant patients are idiotypically connected. Two anti-OKT3
      mAbs G-880 (IgG1) and M-12 (IgM) were derived by immunizing BALB/c mice with the
      OKT3-secreting hybridoma. The two mAbs exhibited specificity for OKT3 F(ab)'2
      idiotypic determinants. Both mAbs were tested for their ability to inhibit OKT3
      induced mitogenesis and to block FITC-OKT3 binding to cell surface CD3 epsilon
      chain. The M-12 mAb inhibited OKT3-induced mitogenesis and blocked (approximately
      60%) the binding of OKT3 to peripheral blood (PBL) T-cell CD3 epsilon chain in
      flow cytometry. In contrast, the G-880 mAb did not inhibit mitogenesis and only
      weakly blocked OKT3 binding to CD3 epsilon chain (approximately 12%). Sera of
      kidney transplant recipients who received OKT3 antirejection therapy and who
      developed antiidiotypic anti-OKT3 antibodies could be divided into two subgroups
      exhibiting anti-OKT3 activity: (a) those who had similar specificity as M-12 and
      failed to enhance the M-12 inhibition of OKT3 binding to PBL T-cell CD3 epsilon
      chain when added as a third component (n = 3), and (b) those with anti-OKT3
      antibodies with idiotype specificity dissimilar to M-12 and who were able to
      increase the (maximum 60%) inhibition obtained with M-12 in the OKT3 to T-cell
      CD3-binding assay (n = 4). From these observations, we conclude that M-12 had the
      characteristics of an Ab2 beta and G-880 that of an Ab2 alpha. Additionally,
      there was an idiotypic connectivity of mouse-derived M-12 anti-OKT3 (Ab2) and
      OKT3-engendered human polyclonal anti-(anti-OKT3) (Ab3), in that three of seven
      patients examined had human serum IgG antibodies that specifically recognized M
      12 idiotypic determinants as demonstrated in ELISA.

PMID- 1386354
TI  - Identification of anti-CD3 antibodies that do not modulate antigen but induce
      mitogenesis and block the mixed lymphocyte reaction.
AB  - Using a panel of anti-CD3-TCR monoclonal antibodies (OKT3 A-E), it appears
      possible to separate the ability to cause surface antigen modulation from
      inhibition of MLR or induction of mitosis. OKT3D, an antibody that recognizes the
      CD3 antigen at a site that can be differentiated from the epitopes recognized by
      other members of this panel by competition binding, does not cause antigen
      modulation when incubated with human T cells for up to 3 days. Despite this,
      OKT3D is mitogenic and is capable of blocking MLR. Two different isotypes were
      produced from the OKT3D clone, IgG1 and IgG2b. The IgG2b isotype of OKT3D blocked
      MLR even in individuals unable to respond mitogenically to this antibody. Use of
      members of this panel may now permit dissection of the types of signals delivered
      by the CD3-TCR complex inducing mitosis, receptor modulation, and other T-cell
      responses.

PMID- 1386356
TI  - What is your diagnosis? Right-sided cardiomegaly associated with supravalvular
      pulmonic stenosis.

PMID- 1386355
TI  - Adriamycin-induced recall of radiation pneumonitis and epilation in lung and hair
      follicles of mouse.
AB  - The influence of Adriamycin and Actinomycin D on the expression of residual
      damage following irradiation of mouse thorax was evaluated. Drugs were given i.v.
      at various times starting on the same day, up to 3 months after irradiation, and
      the mortality from lung damage up to 160 days or epilation up to 98 days after
      irradiation were noted. Adriamycin (1.2 mg/kg in two equal doses), which on its
      own did not cause pneumonitic deaths, did so when combined with doses of local
      thoracic radiation as small as 6 Gy. The dose effect factor was greater if
      Adriamycin was given at 1 or 2 months (1.68) rather than on the same day (1.49).
      A reduction in the latent period to death was also observed with a minimum period
      of 50-60 days after irradiation rather than the normal 80-160 days. Adriamycin
      enhanced the epilation response to radiation, but only at or above threshold
      radiation doses. There was no reduction in the latency. Actinomycin D had no dose
      modifying effects on the radiation response of both lung and hair follicles. The
      interaction between irradiation and Adriamycin seen when the interval between the
      two modalities is long, as it was in this study, may be mechanistically similar
      to the "radiation recall" phenomenon described in the clinic.

PMID- 1386358
TI  - Maturation of murine erythroleukemia cells committed to differentiation requires
      protein kinase C.
AB  - Treatment of murine erythroleukemia cells (MELC) attached to fibronectin-coated
      dishes with dimethyl sulfoxide causes the cells to become committed to the
      erythroid differentiation pathway. These cells mature extensively and acquire the
      characteristics of erythroid cells. The cells lose their cell-surface fibronectin
      receptors and accumulate red cell-specific membrane proteins, such as band 3, in
      amounts comparable to those in erythrocytes. Previous studies of MELC have shown
      that the presence of protein kinase C (PKC) is required for commitment to
      differentiation, but that the level of PKC activity declines progressively during
      maturation. In this study, we have established a role for PKC in the maturation
      of MELC committed to differentiation. Our results show that down-regulation of
      PKC by addition of phorbol 12-myristate 13-acetate (PMA) to committed MELC blocks
      subsequent maturation of the cells. Treatment of MELC with the PKC inhibitors H7
      and sphingosine had similar effects. Down-regulation of PKC was assayed by
      measuring cytosolic PKC activity as well as by Western blotting using PKC
      antibodies. MELC maturation was monitored by loss of the cell-surface fibronectin
      receptor, release of cells from fibronectin plates, and accumulation of the band
      3 anion transport protein. Immunoprecipitation of surface-labeled proteins by an
      anti-fibronectin receptor (integrin) antibody showed that PMA-treated cultures
      had more fibronectin receptor protein than untreated cultures 6 days post
      induction. As a result, cultures of committed MELC treated with PMA remained
      attached to fibronectin-coated plates, whereas non-PMA-treated cells were
      released into the culture medium. Furthermore, PKC-depleted cells accumulated
      much smaller amounts of band 3 protein and band 3 mRNA than did non-PKC-depleted
      controls. Our results show that although PKC activity declines progressively
      during post-commitment maturation of MELC, its continued presence is critical for
      the process of cellular maturation.

PMID- 1386359
TI  - The effects of sphingosine on sarcoplasmic reticulum membrane calcium release.
AB  - In this study, we report that sphingosine is a potent inhibitor of sarcoplasmic
      reticulum (SR) calcium release. Evidence is presented demonstrating a direct
      effect of sphingosine on the SR ryanodine receptor. Calcium release from
      "skinned" rabbit skeletal muscle fibers and isolated junctional SR derived from
      the terminal cisternae (TC) was measured in response to caffeine, doxorubicin, 5'
      adenylyl-beta,gamma-imidodiphosphate or calcium. Sphingosine inhibited caffeine
      induced release in a dose-dependent manner with an IC50 of 0.1 microM for the
      single muscle fibers and 0.5 microM for the isolated TC vesicles. Near complete
      blockage of TC calcium release rate was observed with 3 microM sphingosine.
      Neither sphingomyelin nor sphingosylphosphorylcholine had any effect at the 3
      microM level, suggesting that the sphingosine effect was specific. Doxorubicin
      induced calcium release and spontaneous calcium release were also blocked by
      sphingosine. Sphingosine was also capable of stimulating calcium transport in the
      isolated TC vesicles without an effect on Ca-ATPase activity. Ruthenium red was
      not capable of substantial additional stimulation of calcium transport nor
      inhibition of calcium release beyond the action of sphingosine. Sphingosine's
      blockage of calcium release was not reversed by the protein kinase inhibitor, 1
      (5-isoquinolinesulfonyl)-2- methylpiperazine dihydrochloride, suggesting that the
      action of sphingosine on calcium release was not dependent on ryanodine receptor
      phosphorylation. Sphingosine significantly increased (8-fold) the Kd for specific
      [3H]ryanodine binding to TC membranes and decreased the Bmax with a dose
      dependence similar to the inhibition of calcium release, but sphingosine did not
      affect the pCa tension relationship of skinned skeletal muscle fibers. These data
      are consistent with a direct effect of submicromolar sphingosine on the ryanodine
      receptor. Substantially higher concentrations of sphingosine (30-50 microM) or
      sphingosylphosphorylcholine (10-20 microM) were capable of inducing calcium
      release by themselves. Preliminary data indicate that the transverse tubule and
      not the SR contain substantial sphingomyelinase activity consistent with a
      transverse tubule source of sphingosine production. Considering that sphingosine
      is found in micromolar concentrations in some cells, our data indicate that
      sphingosine generated by the transverse tubule membranes may be a physiologically
      relevant mechanism for modulating SR calcium release.

PMID- 1386357
TI  - Factor I-dependent inactivation of human complement C4b of the classical pathway
      by C3b/C4b receptor (CR1, CD35) and membrane cofactor protein (MCP, CD46).
AB  - Proteolytic inactivation of C4b is a crucial step for regulation of the classical
      complement pathway. A plasma protease factor I and membrane cofactors, C3b/C4b
      receptor (CR1) and membrane cofactor protein (MCP), participate in the regulation
      of cell-bound C4b although the physiological potency of these cofactors remains
      unknown. We have examined the optimal conditions of the factor I-mediated C4b
      regulatory system using purified cofactors. CR1 being a cofactor at a
      cofactor/C4b ratio less than 0.1 (w/w), fluid phase C4b, and methylamine-treated
      C4 (C4ma) were degraded by factor I into C4bi: minimal Cd4 was generated in the
      fluid phase. Liposome-bound C4b (LAC4b), on the other hand, was degraded into C4c
      and C4d. CR1 showed two optimal pHs (6.0 and 7.5) for fluid phase C4b, but one
      (6.0) for LAC4b, and in both cases low conductivity conditions enhanced the C4bi
      generation. CR1 cofactor activity was barely influenced by the NP-40
      concentration. On the other hand, MCP degraded C4b and C4ma, as a factor I
      cofactor, more efficiently into C4c and C4d. Though MCP cofactor activity, like
      that of CR1, was enhanced under low conductivity conditions, it has only one
      optimal pH, 6.0, in both fluid and solid phases. Furthermore, as in the case of
      C3b cleavage, a sufficient NP-40 concentration to solubilize membrane was needed
      for MCP to express full cofactor activity for C4b, in contrast to CR1. MCP was
      less potent for C4b inactivation than for C3b inactivation, while CR1 acted as a
      slightly more effective cofactor for C4b cleavage than for C3b cleavage.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1386360
TI  - Arginine transport in mitochondria of Neurospora crassa.
AB  - Transport of arginine into mitochondria of Neurospora crassa has been studied.
      Arginine transport was found to be saturable (Km = 6.5 mM) and to have a pH
      optimum of pH 7.5. Mitochondrial arginine transport appeared to be facilitated
      transport rather than active transport because: (i) the arginine concentration
      within the mitochondrial matrix after transport was similar to that of the
      reaction medium, and (ii) uncouplers and substrates of oxidative phosphorylation
      did not affect the transport rate. The basic amino acids ornithine, lysine, and D
      arginine inhibited arginine transport. The arginine transport system could be
      irreversibly blocked by treating mitochondria with the reactive arginine
      derivative, N-nitrobenzyloxycarbonyl-arginyl diazomethane.

PMID- 1386361
TI  - Cloning, sequencing, and expression of the Escherichia coli peptide methionine
      sulfoxide reductase gene.
AB  - The gene encoding peptide methionine sulfoxide reductase was cloned from an
      Escherichia coli genomic library using an oligonucleotide probe based on the
      amino-terminal sequence of the protein. The nucleotide sequence revealed that the
      gene codes for a polypeptide of 212 amino acid residues with a calculated
      molecular weight of 23,314. The protein has been overexpressed in E. coli and is
      present as a soluble active species.

PMID- 1386362
TI  - The role of arrestin and retinoids in the regeneration pathway of rhodopsin.
AB  - Phototransduction results from a cascade of reactions that culminate in a
      neuronal signal. Photoisomerization of rhodopsin's chromophore, 11-cis-retinal to
      all-trans-retinal, leads to the formation of the activated photoproduct
      metarhodopsin II (Meta II). Subsequently, Meta II initiates the excitation events
      by activating many copies of the rod cell-specific G-proteins (Gt or transducin).
      To terminate the signal, the long-lived Meta II must be quenched. Deactivation of
      Meta II involves phosphorylation by rhodopsin kinase followed by the binding of
      arrestin. In order to recycle rhodopsin for phototransduction, arrestin must
      dissociate, and the chromophore must be replaced. In this study, we show that the
      reduction of the photolyzed chromophore all-trans-retinal to all-trans-retinol is
      essential for recycling photoactivated rhodopsin. Once this reduction has
      occurred, the arrestin blockade of the receptor is removed, the chromophore site
      becomes accessible for regeneration, and the phosphates can be hydrolyzed. If the
      reduction does not occur, we demonstrate that free all-trans-retinal can react
      with the apoprotein to form pseudo-photoproducts that are spectrally identical to
      the photoinduced metarhodopsin species (Meta I/II/III). The Meta II-like product,
      M380, interacts tightly with arrestin and kinase, however, it does not measurably
      interact with Gt. The persistent blockade by arrestin and the low affinity for Gt
      together prevent activation of the visual cascade. Therefore, any insufficiency
      in the reduction of all-trans-retinal to all-trans-retinol may lead to the
      accumulation of M380-arrestin in situ, which may effect adaptational processes.

PMID- 1386363
TI  - Regulation of sarco-endoplasmic reticulum Ca(2+)-ATPases during platelet-derived
      growth factor-induced smooth muscle cell proliferation.
AB  - The role of the sarco-endoplasmic reticulum Ca(2+)-ATPases (SERCA) in the
      regulation of cell proliferation by Ca2+ was investigated by testing the effect
      of platelet-derived growth factor (PDGF) on cultured pig aorta smooth muscle
      cells. For this purpose, the PDGF-mediated rise in the Ca2+ concentration was
      first examined for its ability to induce the formation of prostaglandins from the
      specific membrane enzyme, cyclooxygenase. In parallel experiments, similar
      conditions (10 ng/ml PDGF for 24 h) were used to investigate the smooth muscle
      cell membrane SERCA2 isoforms. Total SERCA2 activity rose by 472% as reflected by
      their specific formation of phosphorylated intermediate (E approximately P). This
      rise correlated with an increase in the amount of SERCA2 proteins (100 kDa) as
      shown by Western blotting. With isoform-specific anti-SERCA2-a and anti-SERCA2-b
      antibodies, we demonstrated that the increase in total SERCA2 proteins concerned
      the minor isoform SERCA2-a, which rose 10-fold, whereas SERCA2-b proteins were
      not affected. Lastly, Northern blotting using riboprobes showed that PDGF
      treatment increased the SERCA2-a mRNA species by 82%, and concomitantly decreased
      the SERCA2-b mRNA by 28%, as a result of isoform switching. We conclude that up
      regulation of the SERCA2-type Ca(2+)-ATPases occurs in PDGF-treated smooth muscle
      cells, which suggests that this enzymatic system plays an essential part in cell
      proliferation.

PMID- 1386364
TI  - Interleukin 1 induces NF-kappa B through its type I but not its type II receptor
      in lymphocytes.
AB  - It is not known whether one or both of the interleukin 1 (IL1) receptors mediates
      the induction of the DNA-binding protein NF-kappa B. Nuclear extracts of the
      murine lines EL4.NOB.1 and 70Z/3, which bear the type I (80 kDa) and type II (67
      kDa) IL1 receptor, respectively, were analyzed by an electrophoretic mobility
      shift assay. A 265-base pair sequence of the human serum amyloid A gene or a
      synthetic oligonucleotide each containing the NF-kappa B site were used as the
      DNA probes. IL1 induction of NF-kappa B was rapid (optimal at 15-30 min) and
      transient in both cell types. The IL1 receptor antagonist (IL1ra), which binds
      strongly to the type I receptor, inhibited the NF-kappa B response in both cell
      lines. IL1ra did not bind to the type II receptor on 70Z/3 cells as judged by
      competition for binding with 125I-IL1 alpha. When 125I-IL1ra binding to 70Z/3
      cells was measured, a small number (10/cell) of high affinity sites (Kd = 5 x 10(
      12) M) were detected. These were likely to have been type I receptor because an
      antibody to this inhibited the NF-kappa B induction in 70Z/3 cells (as well as
      EL4). Potential signal transduction mechanisms involving protein kinase C or
      oxygen radicals were studied. Phorbol 12-myristate 13-acetate induced NF-kappa B
      with a similar time course to IL1 in 70Z/3 but only after 4 h in EL4.IL1 was
      unaffected by a protein kinase C inhibitor (staurosporine). H2O2 did not mimic
      IL1, and IL1 was not inhibited by an antioxidant. The type I receptor mediates
      the induction of NF-kappa B in response to IL1 via a signaling mechanism that
      still remains to be identified.

PMID- 1386366
TI  - Characterization of a P-type Ca(2+)-ATPase from Flavobacterium odoratum.
AB  - In most bacterial cell types studied, low intracellular free calcium is
      maintained by a variety of secondary exchangers which utilize transmembrane ion
      gradients. Prokaryotic calcium ATPases appear to be extremely uncommon, and none
      have been reported in Gram-negative organisms. We demonstrate ATP-dependent
      calcium uptake in everted membrane vesicles of Flavobacterium odoratum, a common
      Gram-negative soil and water bacterium. Calcium is transported with an apparent
      initial rate of 10 nmol/min mg of protein. It is inhibited by 20 microM
      orthovanadate, a specific P-type ATPase inhibitor, but significantly, it is
      unaffected by the addition of N-ethylmaleimide, N,N-dicyclohexylcarbodiimide,
      valinomycin, or nigericin. Because the Ca(2+)-ATPase makes up a high proportion
      of the total ATPase activity it is easily detected by a soluble ATP hydrolysis
      assay, with an initial rate for calcium-dependent ATPase activity in vesicles of
      25-40 nmol/min.mg at pH 7.8 and 25 degrees C. The calcium-dependent activity is
      preferentially solubilized by the detergent C12E8 and can be precipitated at 55
      80% ammonium sulfate in a fraction free of other contaminating ATPase activities.
      This partially purified fraction is enriched 15-fold and demonstrates an apparent
      Km for calcium of 2 microM, and for ATP of 130 microM. The IC50 for vanadate is
      1.6 microM. These values are similar to those obtained for the eukaryotic
      sarcoplasmic reticulum calcium ATPase. The enzyme is rapidly phosphorylated by
      [gamma-32P]ATP in a calcium-dependent, vanadate-inhibitable manner. The
      phosphorylated species migrates with an apparent molecular mass of 60 kDa by
      NaDodSO4-polyacrylamide gel electrophoresis, and the phosphoryl group is
      sensitive to alkaline conditions, a characteristic of the acylphosphate linkage
      found in ATPases. These data demonstrate that the majority of calcium transport
      in F. odoratum is facilitated by a P-type ATPase.

PMID- 1386365
TI  - Chromosomal localization and organization of the murine genes encoding the beta
      subunits (AIC2A and AIC2B) of the interleukin 3, granulocyte/macrophage colony
      stimulating factor, and interleukin 5 receptors.
AB  - Chromosomal genes for two mouse homologous beta subunits (AIC2A and AIC2B) of the
      interleukin-3, granulocyte/macrophage colony-stimulating factor, and interleukin
      5 receptors were characterized. Both AIC2A and AIC2B genes were present on a 250
      kilobase MluI restriction fragment and were mapped on murine chromosome 15 (these
      loci were provisionally designated as Il3rb-1 (AIC2A) and Il3rb-2 (AIC2B)),
      closely linked to the c-sis locus. Both genes consist of 14 exons and span about
      28 kb each. The major transcription initiation sites of both genes were mapped at
      194 bp from the initiation codon. These genes are 95% identical up to 700 bp from
      the transcription initiation sites. Potential recognition sequences for
      hemopoietic transcription factors including GATA-1 and PU.1 in addition to a TATA
      like sequence are present in the 5'-flanking region. A stretch of 20 bp including
      the initiation site is homologous to the corresponding region of the
      erythropoietin receptor and the interleukin-7 receptor genes and to the initiator
      sequence of the adeno-associated virus P5 promoter, suggesting a possible role in
      transcription initiation. Comparison of the exon/intron boundaries of AIC2A and
      AIC2B genes with those of other members of the cytokine receptor superfamily
      reveals a conserved evolutionary structure. Isolation of various forms of AIC2
      cDNAs reveals differential splicing of the transcripts.

PMID- 1386369
TI  - Phage typing of coagulase-negative staphylococci.
AB  - Seventy-nine staphylococcal strains isolated from blood cultures (57 coagulase
      negative staphylococci (CNS) and 22 S. aureus) and 308 CNS isolated from the skin
      of healthy donors were phage typed. S. epidermidis and S. capitis were readily
      typed with 91 strains out of 124 and 24 strains out of 43 strains being
      successful. Species such as S. haemolyticus, S. hominis and S. simulans could be
      moderately phage typed. Others gave only a few strains capable of being typed,
      such as S. saprophyticus and S. sciuri. Under our experimental conditions the S.
      warneri, S. xylosus and S. cohnii could not be typed with our set of phages.

PMID- 1386367
TI  - Phosphorylation of myosin-II regulatory light chain by cyclin-p34cdc2: a
      mechanism for the timing of cytokinesis.
AB  - To understand how cytokinesis is regulated during mitosis, we tested cyclin
      p34cdc2 for myosin-II kinase activity, and investigated the mitotic-specific
      phosphorylation of myosin-II in lysates of Xenopus eggs. Purified cyclin-p34cdc2
      phosphorylated the regulatory light chain of cytoplasmic and smooth muscle myosin
      II in vitro on serine-1 or serine-2 and threonine-9, sites known to inhibit the
      actin-activated myosin ATPase activity of smooth muscle and nonmuscle myosin
      (Nishikawa, M., J. R. Sellers, R. S. Adelstein, and H. Hidaka. 1984. J. Biol.
      Chem. 259:8808-8814; Bengur, A. R., A. E. Robinson, E. Appella, and J. R.
      Sellers. 1987. J. Biol. Chem. 262:7613-7617; Ikebe, M., and S. Reardon. 1990.
      Biochemistry. 29:2713-2720). Serine-1 or -2 of the regulatory light chain of
      Xenopus cytoplasmic myosin-II was also phosphorylated in Xenopus egg lysates
      stabilized in metaphase, but not in interphase. Inhibition of myosin-II by cyclin
      p34cdc2 during prophase and metaphase could delay cytokinesis until chromosome
      segregation is initiated and thus determine the timing of cytokinesis relative to
      earlier events in mitosis.

PMID- 1386368
TI  - Synergistic actions of epidermal growth factor-urogastrone and vasopressin in
      cultured aortic A-10 smooth muscle cells.
AB  - In cultured rat aorta-derived A-10 cells, epidermal growth factor-urogastrone
      (EGF-URO) acts synergistically with arginine vasopressin (AVP) to augment the AVP
      mediated release of 3H-arachidonate (3H-AA) from 3H-AA prelabeled cells. On its
      own, EGF-URO had no effect on AA release and had no effect on calcium influx or
      efflux either in the absence or presence of AVP. The synergistic action of EGF
      URO was not affected by actinomycin D, cycloheximide, indomethacin, by the
      diacylglycerol lipase inhibitor U-57,908, or by the tyrosine kinase inhibitors
      genistein (GS) and tyrphostin (TP). TP did, nonetheless, completely abrogate 3H
      thymidine incorporation triggered in the presence of EGF-URO. Although EGF-URO
      stimulated an increase in calpactin-II (lipocortin-I) phosphorylation in
      permeabilized cells, no such increase was detected in intact cells exposed to EGF
      URO either alone or in combination with AVP, under conditions where EGF-URO
      augmented the action of AVP. The phospholipase A2 inhibitor, mepacrine, had no
      effect on AVP-mediated AA release, but abolished the synergistic action of EGF
      URO. We conclude that in contrast with our previous results with gastric smooth
      muscle strips, wherein EGF-URO acts via the diacylglycerol lipase-mediated
      metabolism of diacylglycerol, and in keeping with observations with cultured
      mesangial cells, EGF-URO acts synergistically with AVP in A-10 cells via the
      activation of phospholipase A2. This synergistic action of EGF-URO does not
      appear to be due to increased levels of cyclooxygenase and would appear not to
      require increased tyrosine kinase activity.

PMID- 1386371
TI  - Use of direct injection precolumn techniques for the high-performance liquid
      chromatographic determination of the retinoids acitretin and 13-cis-acitretin in
      plasma.
AB  - A previously developed highly sensitive high-performance liquid chromatographic
      method for the determination of retinoids, using direct injection of large plasma
      volumes, on-line solid-phase extraction and ultraviolet detection, was improved
      and fully validated for the determination of acitretin and 13-cis-acitretin in
      plasma samples. The addition of acetonitrile to improve the recovery was
      performed on-line by a T-piece, avoiding any cis-trans isomerization which could
      occur when acetonitrile was added prior to storage in the autosampler. About 30
      injections could be made onto one precolumn despite the large injection volume (1
      ml of plasma containing the internal standard). Full automation was attained by
      the use of automated precolumn replacement. In addition, forward- and back-flush
      purging of the precolumn enhanced the longevity of the analytical column. This
      consisted of three coupled C18 columns of 125 mm length each. The quantification
      limit was 0.3 ng/ml, using ultraviolet detection at 360 nm, and the mean inter
      assay precision was 3.8% for the two compounds.

PMID- 1386370
TI  - [Vascular endoprosthesis. A new indication in the surgery of the iliac artery].
AB  - We have used endoprosthesis (Palmaz Schatz) after balloon angioplasty of iliac
      arterial stenoses or thromboses, in order to increase the immediate patency and
      to prevent the recurrence of stenosis. Our series gathers 24 patients operated
      with endovascular procedures over a period of 2 years: 22 men, 2 women--extreme
      ages 42 to 78 years, average age 63.5 years--Clinical stage: 22 at stage I, 1 at
      stage III, 1 at stage IV. Arteriographic findings: 8 primary iliac lesions (6
      stenoses and 2 thromboses), 11 external iliac lesions (stenoses). All these
      lesions were atheromatous. One of them had recurred after angioplasty. Usual
      technique: balloon angioplasty of the stenosis, assessment on a fluoroscopic
      screen and angioscopy of the result, decision to insert the Palmaz Stent if
      defects are seen on the image. Repatency of impassable lesions with a YAG laser
      was carried out in 2 cases. The indication of an endoprosthesis was established
      on the basis of the radiological image in 17 cases, of the angioscopic image in 4
      and systematically in 10 cases of recurrence of stenosis, iliac thrombosis or
      associated surgery. Associated surgery: 2 femoropopiteal bypass grafts, 3
      femorofemoral bypass grafts, 1 deep plasty, 1 superficial femoral recanalization
      with laser, 1 lymbar sympathectomy. Postoperative results: 1 death due to MI (78
      year-old diabetic woman), 1 thrombosis treated with femorofemoral bypass. Middle
      term results: after 6 to 24 months, average time lapse 13 months. The comparison
      of the ankle pressure indices and of the pre- and postoperative sonographic
      findings shows an indisputable hemodynamic improvement.

PMID- 1386372
TI  - Effect of atrial natriuretic peptide on potassium-stimulated aldosterone
      secretion: potential relevance to hypoaldosteronism in man.
AB  - Atrial natriuretic peptide (ANP) has been shown to suppress aldosterone secretion
      under certain circumstances, although the physiological significance of this is
      uncertain. We wondered if ANP would suppress potassium-stimulated aldosterone
      secretion in man and, if so, whether we might find high circulating levels of ANP
      in patients with the syndrome of acquired hypoaldosteronism. We studied seven
      healthy young subjects under two conditions: 1) infusion of KCl (0.5 mmol/kg)
      over 45 min, and 2) KCl infused with ANP (0.01 microgram/kg.min) for 60 min. We
      also evaluated ANP levels in eight elderly subjects with the syndrome of acquired
      hypoaldosteronism, as defined by hyperkalemia (mean serum K+, 5.3 +/- 0.1 mmol/L)
      associated with inappropriately low aldosterone levels (216 +/- 50 pmol/L). In
      the normal subjects, ANP almost completely suppressed the aldosterone response to
      KCl infusion (P less than 0.001, by analysis of variance) despite a similar rise
      in the serum potassium level with KCl alone (0.70 +/- 0.07 mmol/L) and KCl plus
      ANP (0.75 +/- 0.09 mmol/L). PRA fell slightly during KCl plus ANP treatment, but
      did not change during the infusion of KCl alone. ANP levels were approximately
      800 pmol/L during the ANP infusion studies. Endogenous ANP levels in the
      hyperkalemic patients with hypoaldosteronism were markedly elevated at 1186 +/-
      340 pmol/L (compared to 93 +/- 10 pmol/L in healthy elderly controls), a level
      that would be capable of suppressing the potassium-mediated aldosterone response.
      Exogenous infusion of ANP suppressed the aldosterone response to hyperkalemia,
      and ANP levels were found to be markedly elevated in a group of patients with
      hyperkalemia and hypoaldosteronism. We suggest that ANP may contribute to
      clinically significant hypoaldosteronism and hyperkalemia in the syndrome of
      acquired hypoaldosteronism.

PMID- 1386373
TI  - Assessment of growth hormone (GH) axis in Turner's syndrome using 24-hour
      integrated concentrations of GH, insulin-like growth factor-I, plasma GH-binding
      activity, GH binding to IM9 cells, and GH response to pharmacological
      stimulation.
AB  - The GH axis was studied in Turner's syndrome (TS) patients. Thirty-seven
      prepubertal TS patients and 42 normally growing girls (NGG; 5.5-16.3 yr old), of
      whom 13 were prepubertal, were studied by 24-h continuous blood withdrawal and
      provocative tests. The 24-h integrated concentrations of GH (IC-GH), FSH (IC
      FSH), and insulin-like growth factor-I (IC-IGF-I) as well as the IC-IGF-I/IC-GH
      ratio were determined. An increase in IC-GH with age and progression of puberty
      was found in NGG, but not in TS. IC-GH in the NGG was significantly higher than
      that in age-matched TS patients. Estrogen replacement therapy normalized IC-GH
      levels in 6 TS patients in whom these levels were subnormal for age. A positive
      correlation between IC-GH and IC-FSH or IC-estradiol was found in NGG (r = 0.462;
      P less than 0.01), but not in TS patients. The IC-IGF-I/IC-GH ratio was
      significantly higher in the TS than in the NGG group. Serum GH-binding activity
      and serum GH binding to IM9 cells in the TS group did not differ from those in
      the normal group. We hypothesize that the growth retardation of TS results from a
      combination of insufficient GH secretion, mainly due to sex steroid deficiency,
      and an end-organ resistance to IGF-I. IGF-I receptor studies are needed to test
      this speculation about IGF-I resistance.

PMID- 1386374
TI  - Reduction of vasomotor symptoms and bone mineral density loss with combined
      norethindrone and long-acting gonadotropin-releasing hormone agonist therapy of
      symptomatic endometriosis: a prospective randomized trial.
AB  - The hypoestrogenic state induced by gonadotropin-releasing hormone agonists
      (GnRHa) has been shown to suppress symptomatic endometriosis effectively but to
      elicit vasomotor symptoms and loss of bone mineral density. The role of
      norethindrone as a supplement to GnRHa in eliminating such side effects was
      assessed by enrolling 20 patients with symptomatic endometriosis diagnosed
      laparoscopically in a randomized, prospective, double-blinded trial. All patients
      received the long-acting GnRHa leuprolide acetate 3.75 mg im every 4 weeks for 24
      weeks. Ten patients self-administered norethindrone 5 then 10 mg by mouth daily,
      whereas the remainder self-administered placebo tablets. Results of this study
      showed that combination therapy was as effective as GnRHa alone in significantly
      reducing circulating gonadotropin and estrogen levels (P less than 0.01), extent
      of visible endometriotic implants (P less than 0.01), and painful symptoms (P
      less than 0.01). Marked vasomotor and vaginal symptoms experienced by patients
      given GnRHa alone were minimized in those receiving GnRHa with norethindrone.
      Lumbar spine bone mineral density loss, measured by dual energy x-ray
      absorptiometry, was significantly reduced and more completely reversed in
      patients receiving combination therapy (P less than 0.05). A reversible decrease
      in high density lipoprotein-cholesterol and increase in low density
      lipoprotein:high density lipoprotein ratio was noted only in the patients
      receiving combination therapy, but not in those receiving GnRHa only. The
      addition of norethindrone to GnRHa is an effective means of treating symptomatic
      endometriosis while ameliorating side effects induced by GnRHa alone.

PMID- 1386375
TI  - Effects of a long-term treatment with alacepril on left ventricular hypertrophy
      and function in patients with essential hypertension.
AB  - The authors examined the effects of a long-term treatment with the angiotensin
      converting enzyme inhibitor, alacepril, with respect to the reversal of left
      ventricular hypertrophy and the improvement of left ventricular function. Ten
      uncomplicated essential hypertensive patients with left ventricular hypertrophy,
      aged 53 +/- 8 years, were treated with alacepril alone for 12 months. All
      patients underwent echocardiography to to assess left ventricular dimensions and
      function before and after the treatment. After the treatment, blood pressure was
      decreased significantly from 163 +/- 14.1/98 +/- 4.2 to 142 +/- 20.3/86 +/- 11.0
      mm Hg (each, P less than .01), whereas heart rate did not change (66 +/- 6 versus
      69 +/- 8 beats/min). The left ventricular mass index was decreased significantly
      from 146 +/- 27 to 119 +/- 29 g/m2 (P less than .01). Ejection fraction,
      fractional shortening, peak shortening rate, and peak lengthening rate all
      improved significantly after the treatment. There was a significant inverse
      relationship between fractional shortening and end-systolic wall stress before
      the treatment (r = .63, P less than .05), and this relationship did not change
      after the treatment. It is concluded that alacepril improved both left
      ventricular systolic and diastolic function without causing any consistent
      augmentation of left ventricular contractility.

PMID- 1386376
TI  - Long-standing dermatological manifestations in a patient with chronic heavy metal
      intoxication.
AB  - A patient with chronic metal intoxication is described, presenting during four
      years after the cessation of her exposure to industrial substances, maculo
      papular eruptions with several ulcerated lesions and excoriations on her abdomen
      and buttocks. She also had pallor of her face, greyish-dark discoloration of the
      hair, while the fingernails were brittle and sensitive. Scrupulous physical
      examination excluded further cutaneous involvement. The immunological workup
      revealed both phenotypic and functional defects in cellular immunity.

PMID- 1386377
TI  - A case of lymphadenosis benigna cutis of the earlobe: an immunohistochemical
      study.
AB  - We report a 38-year-old woman who developed an erythematous nodule on her earlobe
      after wearing pierced-type 18-carat gold earrings. Biopsy specimens revealed
      dense cellular infiltration predominantly composed of lymphocytes and plasma
      cells in the dermis and subcutaneous tissue with formation of lymph follicles.
      Morphological and immunohistochemical analyses were compatible with lymphadenosis
      benigna cutis.

PMID- 1386379
TI  - Orthognathic surgery for the treatment of chronic self-mutilation of the lips.
AB  - Self-mutilation by lip chewing is an uncommon problem, but may result in severe
      mutilation, infection and loss of tissue, with associated scarring. Many
      modalities of treatment have been proposed in the literature with variable
      success and morbidity to the patient. Alternative techniques involving
      orthognathic surgery to create an anterior open bite are described which may
      result in cessation of self-mutilation. A case is presented with a 13-year follow
      up, the anterior open bite is still present, and no recurrence of self
      mutilation.

PMID- 1386378
TI  - Establishment of stable CD8+ suppressor T cell clones and the analysis of their
      suppressive function.
AB  - Stable CD8+ suppressor T cell (Ts) clones were established by a relatively simple
      method. Keyhole limpet hemocyanin (KLH)-primed spleen cells from C3H mice were
      depleted of B cells and CD4+ T cells by panning and cytotoxic treatment, and the
      resulting CD8+ T cells were periodically stimulated with antigen and irradiated
      syngeneic spleen cells followed by manifestation in interleukin-2 (IL-2)
      containing medium. T cell clones with a definite suppressor function were
      established by limiting dilution. They were defined as classical effector type Ts
      of CD8+ phenotype as they had constant and definite suppressor functions in
      antigen-induced T cell proliferation and specific antibody response against T
      cell-dependent antigens without detectable cytotoxic activity against both
      antigen presenting cells (APC) and helper T cells (Th). They showed no helper
      activity for B cells and produced no detectable helper type lymphokines such as
      IL-2 and IL-4. CD8+ Ts clones were able to inhibit the antigen-induced IL-2
      production of normal and cloned T cells. Their suppressive activity was antigen
      nonspecific and major histocompatibility complex-unrestricted. CD8+ Ts clones
      were also able to suppress the proliferative response of Th clones induced by
      immobilized anti-T cell receptor (TcR) and anti-CD3 mAbs but not the response
      induced by concanavalin A (ConA) and IL-2. All the CD8+ T cell clones established
      independently utilized the TcR V beta 8 gene. Syngeneic antigen presenting cells
      could induce proliferation of these CD8+ clones, which was blocked by anti-CD8
      and anti-I-Ak monoclonal antibody (mAb) but not by anti-class I mAbs. The
      stimulation of CD8+ Ts clones with immobilized anti-CD3 resulted in the release
      of a suppressor factor(s) that potently inhibited the antigen-induced
      proliferation of CD4+ Th clones and the in vitro secondary antibody formation.

PMID- 1386380
TI  - Human muscle cell denervation: the results of a 31-phosphorus magnetic resonance
      spectroscopy study.
AB  - The results presented here demonstrate that there is a major abnormality of high
      and low energy phosphate metabolism in muscle following peripheral nerve damage.
      Using 31-phosphorus magnetic resonance spectroscopy the changes in
      phosphocreatine, adenosine triphosphate, inorganic phosphate and metabolites of
      membrane metabolism could be observed in vivo in human subjects. The data
      indicate that there may be a metabolic myopathy in the muscle cells after nerve
      injury. Further, the metabolic changes did not always return to the control
      level, indicating a persistence of the abnormality. This failure of the metabolic
      function of the cells may be important in determining the ultimate outcome of
      peripheral nerve surgery.

PMID- 1386381
TI  - Educating students with mild handicaps in general classrooms: essential teaching
      practices for general and special educators.
AB  - This study was designed to identify and validate essential teaching practices
      needed by both general and special educators to successfully educate students
      with mild handicaps in general classrooms. An interdisciplinary panel of 105
      experts, evenly divided into university-based and field-based participants from
      35 states, identified 96 of 125 practices in six categories as being essential
      for effective teaching of mainstreamed students with mild handicaps. Based on a
      two-round Delphi procedure, a substantial majority (82%) of these teaching
      practices were seen as being essential for both general and special educators
      across all six rated categories. Panel ratings were significantly higher for
      special educators than general educators on four of the six categories. No
      significant differences in ratings were found for university-based versus field
      based panelists, or for field-based panelists who were professionals directly
      involved in elementary or secondary teaching roles versus administrators,
      supervisors, and consultants. Based on essential teaching practices validated in
      this study, implications for preservice teacher preparation and staff development
      programs for general and special educators are discussed.

PMID- 1386382
TI  - Neuro-ophthalmic features of carotid cavernous fistulas and their treatment by
      endoarterial balloon embolisation.
AB  - The neuro-ophthalmic features of 11 traumatic carotid cavernous fistulas and
      their successful occlusion by endoarterial balloon embolisation is reported.
      Significant improvement in all neuro-ophthalmic signs and symptoms occurred
      following treatment, however, ocular motility deficits persisted in 7 patients.
      All 11 fistulas were occluded and the patency of the internal carotid artery was
      preserved in 9 patients. Though the internal carotid artery was sacrificed in 2
      patients there were no permanent sequelae. Transient complications of the
      procedure occurred in 2 patients.

PMID- 1386383
TI  - A pilot study of N-methyl-D-aspartate (NMDA) antagonist in Parkinson's disease.

PMID- 1386384
TI  - Influences of exposure to cigarette smoke on concentration of nicorandil in
      plasma of rats.
AB  - Influences of acute exposure to cigarette smoke on plasma concentrations of
      nicorandil administered orally and parenterally were investigated in rats by
      HPLC. The animals were exposed to tobacco smoke of two kinds of cigarettes using
      a smoking machine (i.e., the cigarette smoke contained either low or high
      nicotine and tar). The plasma concentration of nicorandil administered orally at
      a dose of 10 mg/kg had a lower absorption phase in two cigarette smoke-exposed
      groups, particularly in the high nicotine and tar-containing cigarette smoke
      exposed group, compared with the nonsmoking control group. The AUC and MRT values
      in a high nicotine and tar-containing cigarette smoke-exposed group were lower
      and higher, respectively, than in the nonsmoking control group. However, there
      was no marked difference in nicorandil plasma concentrations between the
      cigarette smoke-exposed group and the nonsmoking control group when nicorandil
      was administered ip or iv at a dose of 5 mg/kg. These results suggest that
      cigarette smoke exposure causes the suppression or delay of absorption of
      nicorandil from the gastrointestinal tract.

PMID- 1386385
TI  - Comparison of the host ranges and antigenicity of Cryptosporidium parvum and
      Cryptosporidium wrairi from guinea pigs.
AB  - Oocysts of a Cryptosporidium isolate from guinea pigs were not infectious for
      adult mice, but were infectious for two of three newborn calves and for suckling
      mice. However, oocysts isolated from calves or mice infected with guinea pig
      Cryptosporidium were not infectious for guinea pigs. Four isolates of C. parvum
      from calves were incapable of infecting weanling guinea pigs. Microscopic
      examination of tissue from the colon and cecum of suckling guinea pigs inoculated
      with C. parvum revealed sparse infection of some pups. These host range studies
      and previously described differences in 125I-labeled oocyst surface protein
      profiles between Cryptosporidium sp. from guinea pigs and C. parvum suggest they
      are distinct species. We propose the name Cryptosporidium wrairi be retained.
      Studies with monoclonal antibodies indicate that C. wrairi and C. parvum are
      antigenically related.

PMID- 1386386
TI  - Psychosocial factors as predictors for early retirement in patients with chronic
      low back pain.
AB  - The incidence of disability pensions was followed up for an approximate period of
      4.5 yr in 476 patients with chronic low-back pain. Most of the psychosocial
      factors assessed at the beginning of the study predicted subsequent early
      retirement. In the final logistic regression analysis associations with early
      retirement were found for self-employment, free-floating anxiety, internal back
      pain locus of control, beliefs in control by others, and accomplishment of back
      exercises. An early detection of these factors is emphasized.

PMID- 1386387
TI  - Electron microscopic study of (A)BC excinuclease. DNA is sharply bent in the UvrB
      DNA complex.
AB  - Nucleotide excision repair in Escherichia coli is initiated by the UvrA, UvrB and
      UvrC proteins. UvrA is the damage recognition subunit, makes an A2B1 complex with
      the targeting subunit UvrB, and the complex binds to the lesion site; UvrA
      dissociates leaving behind a very stable UvrB-DNA complex that is recognized by
      the trigger subunit, UvrC, and the ensuing UvrB-UvrC heterodimer makes two
      incisions, one on either side of the lesion. Using electron microscopy, we
      investigated the structures of these early A, A-B intermediates on DNA containing
      ultraviolet light photoproducts. UvrA, which is known to bind to DNA as a dimer
      and produce a DNase I footprint of 33 base-pairs does not change the trajectory
      of DNA appreciably. The A2B1 complex clearly shows a bipartite structure and its
      effect on the trajectory of the DNA was not consistently straight or kinked. In
      contrast, the DNA in the preincision UvrB-DNA complex appears to be severely
      kinked; 43% of the molecules are bent by 80 degrees or more, with an average
      bending angle of 127 degrees. It appears that protein-induced bending is an
      important step on the pathway leading to excision of the damaged nucleotide by
      (A)BC excinuclease.

PMID- 1386388
TI  - Nerve growth factor and choline acetyltransferase activity levels in the rat
      brain following experimental impairment of cerebral glucose and energy
      metabolism.
AB  - Intracerebroventricular (ICV) injection of streptozotocin (STZ) has been reported
      to impair cerebral glucose utilization and energy metabolism (Nitsch and Hoyer:
      Neurosci Lett, 128:199-202, 1991) and also to prejudice passive avoidance
      learning in adult rats (Mayer et al.: Brain Res 532:95-100, 1990). It is well
      established that the forebrain cholinergic system, whose integrity is essential
      for learning and memory functions, depends on the target-derived retrograde
      messenger nerve growth factor (NGF). Therefore, we measured NGF and choline
      acetyltransferase (ChAT) activity levels in the forebrain cholinergic system in
      adult rats that had received a single injection of either STZ or artificial
      cerebrospinal fluid into the left ventricle 1 or 3 weeks prior to sacrifice. One
      week after ICV STZ treatment, NGF content was significantly decreased (-32%) in
      the septal region, where NGF-responsive cell bodies are located and NGF exerts
      its neurotrophic action after retrograde transport from NGF-producing targets. In
      contrast, NGF levels in the cortex and hippocampus, which are target regions for
      the basal forebrain cholinergic neurons, and in the brainstem and cerebellum were
      increased (+12% to +47%) within 3 weeks after ICV STZ treatment. The alterations
      in NGF levels were not related to changes in ChAT activity that decreased in the
      hippocampus by only 15%. This might be due to masking effects exerted by
      compensatory NGF-mediated stimulation of ChAT activity in remaining functional
      neurons. It is suggested that impaired behavior which has been observed after STZ
      induced impairment of cerebral glucose and energy metabolism may be at least
      partially related to a diminished capacity of central NGF-responsive neurons to
      bind and/or transport NGF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386389
TI  - The Monfort operation for abdominal wall reconstruction in the prune belly
      syndrome.
AB  - We present our results in correcting the abdominal wall defect in 8 patients with
      the prune belly syndrome using the Monfort operation. Mean patient age at
      operation was 10 years. Four patients also underwent significant concomitant
      operative procedures. There were no early postoperative complications, and the
      mean postoperative stay for those 4 children undergoing abdominal wall
      reconstruction alone was 7.7 days. This operation preserves the umbilicus, and
      strengthens, flattens and thickens the abdominal wall. It produces a narrow
      waisted more normal physique and provides excellent transperitoneal exposure for
      concomitant genitourinary reconstructive procedures.

PMID- 1386390
TI  - John K. Lattimer Lecture. Prepuce presence portends prevalence of potentially
      perilous periurethral pathogens.

PMID- 1386392
TI  - Plasma polyunsaturated fatty acids in liver cirrhosis with or without chronic
      hepatic encephalopathy: a preliminary study.
AB  - Fatty acid levels (from C14:0 to C22:6n3) in plasma lipid fractions were
      prospectively studied in 11 cirrhotic patients with chronic hepatic
      encephalopathy and compared with those in 23 cirrhotic patients without chronic
      hepatic encephalopathy with similar age, sex distribution, and liver and
      nutritional status, and in 11 age- and sex-matched, healthy subjects. Plasma
      lipid fractions were separated by thin-layer chromatography and fatty acids were
      identified by capillary column gas-liquid chromatography. Total n6
      polyunsaturated fatty acid plasma levels were lower in cirrhotic patients--with
      and without chronic hepatic encephalopathy--than in control subjects. In
      addition, arachidonic acid levels, both in total lipids and fractions, were lower
      in patients with than in those without chronic encephalopathy. On the other hand,
      a selective decrease of plasma docosahexaenoic acid (a major component of
      neuronal membranes) was observed in those patients with chronic encephalopathy as
      compared with both control and cirrhotic subjects without chronic encephalopathy.
      These findings may be due to various mechanisms. Differences in long-chain
      polyunsaturated fatty acid content in fish- and meat-restricted diets partly may
      account for these findings. However, it could be speculated that polyunsaturated
      fatty acid biosynthesis may be reduced further in patients with chronic hepatic
      encephalopathy because of either a decrease in portal essential fatty acid
      extraction in the postabsorptive phase due to portal-systemic shunting or to the
      effect of protein-restricted diets. Furthermore, the finding of low plasma
      docosahexaenoic acid in these patients raises the possibility that this
      deficiency might be an additional pathogenic factor in chronic hepatic
      encephalopathy.

PMID- 1386391
TI  - What can the history and physical examination tell us about low back pain?

PMID- 1386393
TI  - Laparoscopic general surgery: current status and future prospects.
AB  - The capability of performing major abdominal surgery while avoiding a large
      abdominal incision has clear benefits for patient care. Laparoscopic
      cholecystectomy can reduce hospital stays and the length of the recovery period,
      as well as decrease postoperative pain, diminish scarring, and provide
      significant cost savings.

PMID- 1386394
TI  - Symposium: compliance and quality in residential life. Foreward.

PMID- 1386395
TI  - Compliance and quality in residential life. Symposium overview: are we making the
      same mistake twice?

PMID- 1386396
TI  - Symposium on compliance and quality in residential life.

PMID- 1386397
TI  - Compliance and quality in residential life. Quality, organization design, and
      standards.
AB  - Regulations and voluntary standards within the context of organizational design
      and mission as well as leadership in management for quality were discussed. Rules
      and regulations are closely associated with the structure and mission of the
      organization. Altering them may require fundamental redesign of organizational
      structure and purpose. Likewise, alterations in organizational design can change
      the need for rules and regulations. In addition, standards do not automatically
      yield quality. Rather, they define expected levels of performance from
      individuals, programs, and the organization. The senior management of
      organizations is responsible for exercising the leadership in managing for
      quality.

PMID- 1386398
TI  - Symposium on compliance and quality in residential life. Getting into the jet
      stream.

PMID- 1386399
TI  - Symposium on compliance and quality in residential life. Seeking success amid
      today's chaotic demands.

PMID- 1386400
TI  - Symposium on compliance and quality in residential life. The paradox of
      regulations: a commentary.

PMID- 1386401
TI  - Partial protection of 1 alpha-hydroxyvitamin D3 against the development of
      diabetes induced by multiple low-dose streptozotocin injection in CD-1 mice.
AB  - 1 alpha-Hydroxyvitamin D3 (1 alpha-OH-D3), a precursor of active vitamin D3, 1
      alpha,25-dihydroxyvitamin D3, was tested in CD-1 mice for its in vivo effect
      against the development of diabetes induced by administering multiple low doses
      of streptozotocin (STZ). Daily intraperitoneal (IP) injections of 35 mg/kg body
      weight of STZ administered for 5 consecutive days to mice from 7 weeks of age
      induced a delayed-onset hyperglycemia, insulitis, and beta-cell degranulation in
      26 of 28 mice. Only 12 of 29 mice developed diabetes when treated with
      simultaneous daily IP injections of 1 alpha-OH-D3 for 14 consecutive days, with
      diabetes defined as a plasma glucose level greater than 200 mg/dL. A daily dose
      of 0.3 micrograms/kg 1 alpha-OH-D3 also protected against the development of
      hyperglycemia in five of 13 mice, whereas 0.2 micrograms/kg 1 alpha-OH-D3 was
      ineffective, indicating a dose-related effect. Histological study showed that,
      among the 1 alpha-OH-D3-treated mice, the pancreatic islets of euglycemic mice
      showed neither massive islet infiltration nor beta-cell degranulation, whereas
      those of the hyperglycemic mice showed insulitis. However, when diabetes was
      chemically induced with a single high dose of STZ, the simultaneous
      administration of 1 alpha-OH-D3 to mice failed to protect against the development
      of hyperglycemia; all five mice so treated developed hyperglycemia. Their
      pancreatic islets did not show insulitis. Therefore, it is suggested that 1 alpha
      OH-D3 may protect against the development of diabetes following administration of
      multiple low doses of STZ, probably via an immune mechanism.

PMID- 1386402
TI  - The influence of dietary carbohydrate and deferoxamine on developing copper
      deficiency of rats.
AB  - The present investigation was conducted to follow the development of copper
      deficiency in male rats from weaning (day 0) to day 31 of dietary copper
      deprivation and to correlate changes in tissue sizes with copper and iron
      concentrations. Male rats were fed for 31 days from weaning copper-deficient or
      adequate diets containing fructose or starch. Another copper-deficient group of
      rats that was fed fructose was treated with deferoxamine. Rats were killed at day
      0, 8, 16, 24, and 31 of the study. In general, no correlation could be found
      between the development of heart hypertrophy, pancreatic and thymic atrophy, and
      tissue copper concentrations in copper-deficient rats fed fructose. In contrast,
      in the heart and pancreas a negative correlation existed between tissue size and
      iron concentration. In addition, anemia preceded heart hypertrophy. Deferoxamine
      lowered hepatic iron concentrations, ameliorated the anemia, and decreased heart
      size compared with untreated rats. The data of the present study suggest that
      tissue atrophy and hypertrophy and the severity of copper deficiency are not
      solely due to tissue concentrations of iron and/or copper.

PMID- 1386403
TI  - Plasma lipoprotein(a) concentration in familial hypercholesterolemic patients
      without coronary artery disease.
AB  - Familial Hypercholesterolemia (FH) is a condition characterized by markedly
      elevated blood cholesterol, low-density lipoproteins (LDL), and apolipoprotein B
      100 (apo B). The molecular basis of this monogenic disease is the defective
      functioning of the cellular receptor for LDL that recognizes apo B.
      Lipoprotein(a) [Lp(a)] is a circulating lipoprotein that is structurally related
      to LDL, as it also contains apo B. To assess the impact of the LDL receptor
      deficiency on the plasma Lp(a) concentration, we measured Lp(a) in 28 FH patients
      and in 31 unaffected relatives. Because elevation of Lp(a) concentration in
      plasma of patients with coronary artery disease (CAD) appears to occur
      independently from plasma cholesterol levels, to avoid potentially confounding
      problems, members of the families chosen had no history for the disease. Whereas
      apo B clearly showed a bimodality of distribution by being significantly higher
      in the FH patients (166 +/- 38 mg/dL) than in the unaffected relatives (92 +/- 18
      mg/dL), Lp(a) concentration did not differ in the two groups of patients (30 +/-
      24 mg/dL in the FH patients v 31 +/- 23 in the normolipidemic relatives). Similar
      results were obtained when only siblings were further considered. We conclude
      that although Lp(a) is closely related to LDL structurally, its level in plasma
      is not significantly affected by the LDL receptor activity.

PMID- 1386404
TI  - Treatment of hypothyroidism reduces low-density lipoproteins but not
      lipoprotein(a).
AB  - Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which
      apolipoprotein B-100 (apo B) is attached to a large plasminogen-like protein
      called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined
      phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma
      are inversely correlated. LDL and apo B levels are often elevated in untreated
      hypothyroidism and lowered by thyroxine (T4) treatment, probably due to an
      increase in LDL receptors. We measured plasma concentrations of LDL, apo B, and
      Lp(a) in 13 patients with symptomatic primary hypothyroidism before and during T4
      therapy. The mean concentration of LDL decreased significantly (P = .006) from
      6.05 mmol/L to 4.07 mmol/L, and the mean concentration of apo B decreased
      significantly (P = .005) from 1.42 g/L to 1.12 g/L. Median Lp(a) concentrations
      remained unchanged (P = .77); they were 17.05 mg/dL before and 16.59 mg/dL during
      T4 treatment. In both the untreated condition and during substitution therapy,
      Lp(a) levels were higher in patients than in healthy controls, probably due to a
      relatively high frequency of the small Lp(a) phenotypes in our patients. Since
      Lp(a) contains apo B, which is a ligand for the LDL receptor, it is surprising
      that Lp(a) is not reduced along with LDL and apo B. These findings suggest that
      the catabolism of LDL and Lp(a) differ in some respect, and that thyroid hormones
      have little, if any, effect on Lp(a).

PMID- 1386405
TI  - Alternative histochemical markers for skeletal muscle capillaries: a statistical
      comparison among three muscles.
AB  - Except in thin muscles, the analysis of muscle capillary depends on direct
      ultrastructural visualization or histochemical identification of the capillaries
      using stains for basement membrane or reactions for endothelial cell enzymes. The
      accuracy of existing histochemical methods for detecting capillaries has not been
      systematically tested, however. The purpose of the present study was to compare
      muscle capillarity determined by two methods currently in use, Griffonia
      simplicifolia I lectin (GSI) and ATPase, with two alternative capillary markers,
      Lycopersicon esculentum lectin (LEA) and MRC OX.43 antigen. Capillarity,
      expressed as capillaries around fibers (CAF), was determined in the soleus,
      extensor digitorum longus, and sternomastoid muscles from 4-month-old female
      rats. The GSI, LEA, and MRC OX.43 capillary markers gave identical results for
      each muscle, confirming their validity as cytochemical probes. In contrast, the
      capillary ATPase method gave significantly lower CAF determinations, with a
      differential effect of preincubations at pH 4.4 vs 4.0. These data suggest that
      capillary ATPase acid stability varies within the capillary bed. The use of one
      or more of the alternative capillary markers tested is suggested for studies of
      muscle capillarity to confirm that binding sites or enzyme activity used for a
      given probe is expressed under both control and experimental conditions.

PMID- 1386406
TI  - Transition time control analysis of a glycolytic system under different glucose
      concentrations. Control of transition time versus control of flux.
AB  - Control and Response Coefficients of transition time have been determined in a
      rat liver glycolytic system under different glucose concentrations. Results have
      been compared with the Flux Control and Flux Response Coefficients measured in
      the same conditions, showing that transition time and flux are different
      responses of the system, subject to different regulation and control. Control
      Coefficients of flux and transition time show a very different profile in each
      condition of glucose concentration assayed. Ratio of Flux Control coefficients of
      glucokinase over phosphofructokinase at 5 and 20 mM glucose concentration changes
      from 3.2 to 0.5, while the same ratio in the case of Transition Time Control
      Coefficients moves from 0.6 to 0.93. Moreover, the absolute values of Transition
      Time Control Coefficients in glycolytic conditions are one order of magnitude
      bigger than in gluconeogenic conditions. Values of Response Coefficients also
      show that the transition time has a bigger sensitivity to changes in glucose
      concentration than the flux in all conditions assayed, but particularly in
      glycolytic ones.

PMID- 1386407
TI  - Prenatal diagnosis--when and how?

PMID- 1386408
TI  - Tyrosine-containing motif that transduces cell activation signals also determines
      internalization and antigen presentation via type III receptors for IgG.
AB  - Type III receptors for IgG (Fc gamma RII; ref. 1), high-affinity IgE receptors
      (Fc epsilon RI; ref. 2), as well as the T- and B-cell antigen receptors, consist
      of multiple components with specialized ligand-binding and signal transduction
      functions. Fc gamma RII alpha (ligand-binding) and gamma (signal-transducing)
      subunits are expressed in macrophages, a cell type involved in the uptake of
      antigen, its processing and the presentation of the resulting peptides to major
      histocompatibility complex class II-restricted T lymphocytes. Here we show that
      murine Fc gamma RIII, transfected into Fc gamma R-negative antigen-presenting B
      lymphoma cells, mediate rapid ligand internalization and strongly increase the
      efficiency of antigen presentation when antigen is complexed to IgG. Efficient
      internalization and antigen presentation via Fc gamma RIII did not require the
      cytoplasmic domain of the ligand-binding alpha-chain, but did require the gamma
      subunit. Using chimaeric molecules, we show that gamma-chain contains a signal
      for receptor internalization and that the mutation of either of the two tyrosine
      residues present in its cytoplasmic domain prevents efficient internalization and
      antigen presentation of immune complexes. Thus, associated chains and their
      tyrosine-containing motif are not exclusively involved in cell activation, but
      also determine multimeric receptor internalization.

PMID- 1386409
TI  - CD21 is a ligand for CD23 and regulates IgE production.
AB  - The molecule CD23, a low-affinity receptor for IgE (Fc epsilon R2), is a type II
      transmembrane molecule expressed on many haemopoietic cell types. CD23 has
      pleiotropic roles in the control of lymphocyte behaviour, suggesting that CD23
      may interact with another ligand in addition to IgE. To identify such a CD23
      ligand, we expressed and purified full-length recombinant CD23, incorporated it
      into fluorescent liposomes and used these as a probe. We report here that
      fluorescent liposomes carrying CD23 interact specifically with the cell-surface
      protein CD21, identified as the receptor for Epstein-Barr virus and the
      complement receptor-2 on B cells, some T cells and follicular dendritic cells. In
      addition, fluorescent CD23-liposomes were shown to bind to hamster kidney cells
      (BHK-21) transfected with CD21 complementary DNA. The interaction between
      fluorescent CD23-liposomes and B cells or CD21-transfected BHK-21 cells was
      specifically inhibited by anti-CD21 and anti-CD23 monoclonal antibodies. Western
      blotting analysis revealed that 14C-labelled liposomes carrying CD23, in contrast
      to anti-CD21 antibodies, reacted with a subtype of CD21 molecules. Triggering of
      CD21 either with an anti-CD21 antibody or with recombinant soluble CD23 was shown
      to increase specifically interleukin-4-induced IgE production from blood
      mononuclear cells. These results demonstrate that the cell-surface protein CD21
      is a ligand for CD23 and that the pairing of these molecules may participate in
      the control of IgE production.

PMID- 1386411
TI  - [Social insurance medicine in The Netherlands].

PMID- 1386410
TI  - Evidence for a viral superantigen in humans.
AB  - Superantigens bind class II major histocompatibility proteins and stimulate
      powerful proliferative responses of T lymphocytes bearing particular V beta
      sequences as part of their alpha beta antigen receptor. Exogenous bacterial
      superantigens are responsible for food poisoning and toxic shock syndrome. Murine
      virus-encoded self-superantigens induce clonal deletion of T lymphocytes.
      Although superantigen-like properties have been suggested for human
      immunodeficiency virus-1, no viral superantigen has been identified in humans.
      Here we report that the nucleocapsid of the rabies virus is an exogenous
      superantigen specific for V beta 8 human T lymphocytes which binds to HLA class
      II alpha-chains.

PMID- 1386412
TI  - [Cholecystectomy and bile duct lesions].

PMID- 1386413
TI  - Atrial and brain natriuretic peptides enhance dopamine accumulation in cultured
      rat hypothalamic cells including dopaminergic neurons.
AB  - Dopamine accumulation in hypothalamic cells by atrial natriuretic peptide (ANP)
      and brain natriuretic peptide (BNP) was analyzed using newborn rat hypothalamic
      cells in culture. Both ANP and BNP caused a dose-dependent increase in [3H]
      dopamine accumulation in the cells. ANP increased [3H]-dopamine accumulation
      significantly within 20 min. The effects of ANP and BNP on dopamine accumulation
      paralleled an increase in intracellular cGMP concentration. (Bu)2-cGMP and sodium
      nitroprusside, a stimulator of the soluble form of guanylate cyclase, also
      enhanced [3H]-dopamine accumulation. ANP had no effect on efflux of [3H]
      radioactivity after [3H]-dopamine uptake. These results suggest that a change in
      cGMP is one of the intermediate steps in dopamine accumulation in hypothalamic
      cells by ANP and BNP.

PMID- 1386414
TI  - Distribution of type I interleukin-1 receptor messenger RNA in testis: an in situ
      histochemical study in the mouse.
AB  - The cytokine interleukin-1 (IL-1) has been reported to inhibit the hypothalamic
      pituitary-gonadal axis, both through actions in brain and at the gonadal level.
      Recently, high affinity binding sites for 125I-recombinant human IL-1 alpha have
      been identified in the mouse testis with characteristics similar to those of type
      I IL-1 receptors on T lymphocytes and fibroblasts. The present study employed in
      situ hybridization histochemistry with 35S-labeled antisense cRNA probes derived
      from a murine type I IL-1 receptor cDNA to identify type I IL-1 receptor mRNA in
      the mouse testis. An intense signal was observed over interstitial cells, and
      over the cytoplasm of the epithelium of epididymal ducts, most prominently in the
      head region. The signal over seminiferous tubules, and over sperm cells within
      tubules and epididymal ducts, was comparable to background. This distribution of
      type I IL-1 receptor mRNA was similar to that recently reported for 125(I)I-IL-1
      alpha binding sites, and supports evidence implicating IL-1 as a direct regulator
      of gonadal function.

PMID- 1386415
TI  - A possible involvement of central atrial natriuretic peptide in cerebral cortical
      microcirculation.

PMID- 1386416
TI  - Expression of Fc gamma receptors on astroglial cell lines and their role in the
      central nervous system.
AB  - Astrocytes have been regarded as the matrix of the central nervous system and as
      nutritional, metabolic support to neurons. Recently, immunological roles of
      astrocytes have been reported, especially in multiple sclerosis and experimental
      allergic encephalitis. One observation shows that human glioma cells, which lack
      CD4 molecules, can be infected with human immunodeficiency virus in vitro.
      Another report described that human macrophages can be infected with human
      immunodeficiency virus through Fc gamma receptors expressed on their cell
      surfaces. These results prompted us to examine the functioning molecules,
      especially Fc gamma receptor for immunoglobulin G, expressed on the astroglial
      cell line. From erythrocyte-antibody rosette assays, redirected cytolysis and
      flow cytometric analysis, we have shown that human astrocytoma cell lines possess
      Fc gamma receptors on their cell surfaces. Furthermore, primary cultured murine
      astrocytes express Fc gamma II receptors, reacting with 2.4G2 monoclonal
      antibody. Surprisingly, murine astrocytes prepared from newborn BALB/c mice
      demonstrate killing activity against allogeneic T cell leukemia by antibody
      dependent cellular cytotoxicity. After treatment with the macrophage activating
      factor, interferon-gamma, expression of Fc gamma receptors and killer activity of
      astrocytes were augmented. From these results, it is suspected that the
      astroglial cell lines play an important immunological role in the brain.

PMID- 1386417
TI  - Haloperidol-induced increase in neuropeptide Y immunoreactivity in the locus
      coeruleus of the rat brain.
AB  - The effect of haloperidol, a dopamine (preferably D2) receptor blocking agent on
      neuropeptide Y immunoreactivity was studied immunohistochemically in neurons of
      the locus coeruleus and striatum of rat brain. It was found that haloperidol
      given four times (5 and 2.5 mg/kg, i.p.) induced, after 24 h, a significant
      increase in the level of neuropeptide Y immunoreactivity in the locus coeruleus
      but not in the striatum. No changes in neuropeptide Y immunoreactivity in studied
      structures were observed after alpha-adrenergic receptor blocking agent
      phenoxybenzamine or serotonin-synthesis inhibitor D,L-p-chlorophenylalanine. The
      results suggest that the content of neuropeptide Y-immunoreactive material in
      nerve cell bodies of the locus coeruleus is inhibitorally controlled by
      monoaminergic (may be dopaminergic D2) receptors.

PMID- 1386418
TI  - A dopamine D1 receptor antagonist, SCH 23390, selectively blocks vasopressin
      release after noxious stimuli in the rat.
AB  - Effects of a dopamine D1 receptor antagonist, SCH 23390, were investigated on
      plasma level of vasopressin after stressful stimuli in rats. The antagonist
      markedly attenuated the increase in plasma level of vasopressin after electric
      footshocks but not after s.c. injected hypertonic saline. The antagonist,
      however, did not significantly change the suppressive vasopressin response to
      fear-related emotional stress, though the drug suppressed motor behavior of the
      rat during testing period. These data suggest that dopamine D1 receptors play an
      important role selectively in the facilitatory vasopressin response to noxious
      stimuli in rats.

PMID- 1386419
TI  - Variation in susceptibility of inbred lines of chickens to seven species of
      Eimeria.
AB  - The pattern of oocyst production of 8 inbred lines of chickens was compared for
      each of the 7 species of Eimeria which infect this host. Both the overall numbers
      and the pattern of oocyst production differed in the inbred lines, but there was
      no evidence of prolonged cycling of schizogenic developmental stages. Comparison
      of the numbers of oocysts produced by the different lines indicates that there
      may be common genetic factors affecting susceptibility to 6 of the 7 species.
      Surprisingly there appears to be an inverse relationship between susceptibility
      to E. tenella and susceptibility to the other species: lines which produced most
      oocysts of E. tenella produced least oocysts of the other species and vice-versa.

PMID- 1386420
TI  - Pulmonary dysfunction after primary closure of an abdominal wall defect and its
      improvement with bronchodilators.
AB  - To determine the extent of pulmonary dysfunction following primary closure of an
      abdominal wall defect, we obtained pulmonary function tests (PFT) in 11 newborn
      infants with gastroschisis and 6 with large omphaloceles admitted to a newborn
      ICU in a children's hospital. Patients were 1 to 30 days of age at the time of
      the PFT; all required endotracheal intubation and mechanical ventilation for
      operative procedures or for postoperative ventilatory support. Full-term infants
      (n = 21) undergoing minor surgical procedures provided comparative measurements.
      Flow-volume curves were obtained with manual inflation of the lungs followed by
      forced deflation using negative pressure, or by passive expiration, under
      sedation and pharmacologic paralysis. Deflation flow-volume curves gave
      measurements of forced vital capacity (FVC) and maximal expiratory flow at 25% of
      vital capacity from residual volume (MEF25). Modified passive mechanics technique
      gave passive expiratory curves that provided measurements of respiratory system
      compliance (Crs) and resistance (Rrs). Tests were done: within 48 h (period A), 3
      7 days (period B), and 8-30 days after surgical repair (period C). Pulmonary
      function testing after nebulized 0.1% isoetharine (a bronchodilator), to test for
      bronchial reactivity, began midway during the study period in 15 patients.
      Preoperative and postoperative tests were obtained in 5 patients. Closure of an
      abdominal wall defect decreased FVC, Crs, and MEF25 by up to 50% of normal,
      reference values after surgery (P less than 0.05). FVC and MEF25 approached
      values of normal infants by 4 weeks, whereas Crs remained 50% lower.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1386421
TI  - Control of hepatitis B: to be or not to be?

PMID- 1386422
TI  - Atomic force microscopy of single- and double-stranded DNA.
AB  - A method has been developed for imaging single-stranded DNA with the atomic force
      microscope (AFM). phi X174 single-stranded DNA in formaldehyde on mica can be
      imaged in the AFM under propanol or butanol or in air. Measured lengths of most
      molecules are on the order of 1 mu, although occasionally more extended molecules
      with lengths of 1.7 to 1.9 mu are seen. Single-stranded DNA in the AFM generally
      appears lumpier than double-stranded DNA, even when extended. Images of double
      stranded lambda DNA in the AFM show more sharp kinks and bends than are typically
      observed in the electron microscope. Dense, aggregated fields of double-stranded
      plasmids can be converted by gentle rinsing with hot water to well spread fields.

PMID- 1386423
TI  - U1-U2 snRNPs interaction induced by an RNA complementary to the 5' end sequence
      of U1 snRNA.
AB  - Several lines of evidences indicate that U1 and U2 snRNPs become interacting
      during pre-mRNA splicing. Here we present data showing that an U1-U2 snRNPs
      interaction can be mediated by an RNA only containing the consensus 5' splice
      site of all of the sequences characteristic of pre-mRNAs. Using monospecific
      antibodies (anti-(U1) RNP and anti-(U2) RNP), we have found that a tripartite
      complex comprising U1 and U2 snRNPs is immunoprecipitated in the presence of a
      consensus 5' splice site containing RNA, either from a crude extract or from an
      artificial mixture enriched in U1 and U2 snRNPs. This complex does not appear in
      the presence of an RNA lacking the sequence complementary to the 5' terminus of
      U1 snRNA. Moreover, RNAse T1 protection coupled to immunoprecipitation
      experiments have demonstrated that only the 5' end sequence of U1 snRNA contacts
      the consensus 5' splice site containing RNA, arguing that U2 snRNP binding in the
      tripartite complex is mediated by U1 snRNP.

PMID- 1386424
TI  - RNA binding specificity of a Drosophila snRNP protein that shares sequence
      homology with mammalian U1-A and U2-B" proteins.
AB  - We have characterized a recombinant Drosophila melanogaster RNA binding protein,
      D25, by virtue of its antigenic relationship to mammalian U1 and U2 small nuclear
      ribonucleoprotein (U snRNP) proteins. Sequence analysis revealed that D25 bears
      strong similarity to both the human U1 snRNP-A (U1-A) and U2 snRNP-B" (U2-B")
      proteins. However, at residues known to be critical for the RNA binding
      specificities of U1-A and U2-B" D25 sequence is more similar to U2-B". Using
      direct RNA binding assays D25 selected U1 RNA from either HeLa or Drosophila Kc
      cell total RNA. Furthermore, D25 bound U1 RNA when transfected into mammalian
      cells. Thus, D25 appears to be a Drosophila homolog of the mammalian U1-A
      protein, despite its sequence similarity to U2-B".

PMID- 1386426
TI  - Kinetics of 99mTc-labelled antibodies against CD4 (T-helper) lymphocytes in man.
AB  - The availability of radiolabeled anti-CD4 antibodies permitted the study of their
      kinetic behaviour. Four patients suffering from rheumatoid arthritis were
      investigated prospectively. Three of them received 250 micrograms of 99mTc
      labelled anti-CD4 antibody (MAX.16H5). One patient received in vitro 99mTc
      antibody-labelled lymphocytes. 4% of the activity was excreted by the kidneys.
      From 4 to 24 h the splenic uptake decreased from 7.5 to 4%, the liver uptake
      increased from 25 to 30% the bone marrow uptake remained about the same 50% and
      the uptake of a single diseased joint (2%) increased slightly to 2.5%. 15 to 30
      min after injection of the antibody a redistribution of labelled cells or
      antibody from liver and spleen to the circulating blood seemed to occur. The
      recovery rate (0-1 h) of in vivo labelled cells amounted to 30%, that of in vitro
      labelled cells to 19%. One patient was examined with in vitro labelled CD4
      expressing lymphocytes. There was no difference in the antibody kinetics between
      in vitro and in vivo labelled cells. The authors suggest that circulating CD4
      lymphocytes can be labelled with monoclonal antibodies. The kinetics of these in
      vitro labelled cells and the injected labelled antibody itself resembles that of
      recirculating lymphocytes.

PMID- 1386425
TI  - A new strategy useful for rapid identification of microsatellites from DNA
      libraries with large size inserts.
AB  - Microsatellites are new powerful polymorphic markers used for gene mapping. Their
      characterization requires that all the sequence surrounding the repeat be known
      in order to be able to design primers for PCR amplification. However, when using
      DNA libraries with large cloned inserts, this sequence characterization is not
      immediately practicable. In this paper, we describe a new strategy, based both on
      the use of a microsatellite specific probing and on the creation of nested
      deleted clones with the Exonuclease III, in order to position microsatellites in
      a range allowing direct sequencing. This method was applied to the screening of a
      mouse chromosome 19 DNA specific library. In this way, thirteen clones were
      identified by specific probing and seven were submitted to the nested deletion
      strategy. Five of them presented microsatellite sequences in specific deleted
      subclones which were selected and sequenced. Primers were designed for each of
      them and polymorphism between the genomes of several inbred strain of mouse have
      been determined. These microsatellites were mapped, three of them to chromosome
      19 and two to chromosome 11.

PMID- 1386427
TI  - [Effect of thermal dehydration on blood levels of volume- regulating hormones and
      sweat electrolytes in patients with essential hypertension treated with
      propranolol].
AB  - The present study aims to answer the following questions: 1. do secretion of
      volume related hormones in patients with EH pre- and post treatment with
      propranolol differ from normotensive subjects if examined in thermal dehydration
      conditions; 2. is the electrolyte composition of thermal sweat related to the
      plasma profile of volume related hormones? and 3. does treatment by propranolol
      influence sweat electrolytes in EH patients. In 15 patients with EH and in 20
      healthy subjects a thermal dehydration test was performed. In patients with EH
      this test was done twice: before treatment and after 6 weeks of propranolol
      therapy. In all subjects the plasma renin activity (PRA), aldosterone (Ald), AVP
      and ANP were measured before and after thermal dehydration. In sweat samples
      collected after 15' and 45' of thermal dehydration (the concentration of Na, K
      and Cl was assessed). In hypertensive patients before propranolol treatment
      significantly higher values of PRA, Ald and ANP were found, while sweat
      concentrations of Na and Cl were significantly lower than in controls. After
      propranolol treatment sweat electrolytes concentrations showed a tendency to
      normalize. No significant correlation was found between the plasma hormonal
      profile and sweat Na, K and Cl concentrations respectively both in controls and
      patients with EH pretreatment. A significant positive correlation was noticed
      only in hypertensive patients posttreatment between ANP and sweat potassium
      concentration respectively, and significant negative correlation between PRA and
      sweat sodium and chloride concentration. From results obtained in this paper it
      seemed, that volume related hormones (Ald, AVP, ANP) do not seem to influence
      markedly the electrolyte composition of thermal sweat both in healthy subjects
      and in hypertensive patients.

PMID- 1386428
TI  - [The role of calmodulin and calcium ions in the immunosuppressive mechanism of
      the action of cyclosporin A].
AB  - The calcium pathway of Cyclosporine A (CyA) action on peripheral blood
      lymphocytes was assessed with regard to the literature data and self observations
      of kidney graft recipients. A significant relation between the immunosuppressive
      action of the drug and intracellular concentrations of Ca2+ is intimately linked
      with the regulatory potential of calmodulin. Because of the widespread clinical
      use of calcium channel blockers also considered influence of these drugs on
      immunosuppression by CyA and their importance in reducing its nephrotoxicity.

PMID- 1386429
TI  - [Physiopathology of cutaneous vasculitis].

PMID- 1386430
TI  - [Renovascular arterial hypertension. Evaluation of ultrasonographic measurement
      of kidney length].
AB  - In order to evaluate the ultrasonographic measurement of kidney length, 32
      hypertensive patients with renal arterial stenosis treated by intraluminal
      angioplasty were examined by several ultrasonographies performed by the same
      observer before and after dilatation. The lack of variation in the contralateral
      kidney length ascertained the intra-observer reproducibility of the method. We
      found that ischaemic kidneys were smaller and that this diminution in size
      depended on the renal arterial lesion (kidneys below atheromatous lesions were of
      smaller size than those below fibrodysplastic lesions). The increase in size of
      kidneys treated by angioplasty was most probably due to an increase in perfusion
      pressure and was to be compared with the results of a separate evaluation of
      renal function. However, this method has no individual applications in view of
      the important kidney length distribution at cross-checkings.

PMID- 1386431
TI  - [Malaria and hemoglobin S: interactions in African children].
AB  - Among 300 cases of Plasmodium falciparum malaria attacks explored in Gabon, the
      proportion of homozygous (SS) or heterozygous (AS) sickle-cell patients was 6.2
      percent in 206 ordinary attacks and 3.2 percent in 94 cerebral malaria attacks,
      and 23.2 percent in the general population. On the other hand, asymptomatic
      carriage, as detected in 98 children by thin blood films in school screening, was
      as frequent in the SS or AS infantile population as in the general population.
      These data show that haemoglobin S protects effectively, although not entirely,
      against severe attacks of P. falciparum malaria. The incidence of anaemia and
      vaso-obstructive crisis in malaria-infested sickle-cell patients suggests that
      subclinical carriage of haematozoa may worsen the course of sickle-cell disease,
      and this must be taken into account when planning treatment.

PMID- 1386432
TI  - ["Spontaneous" ischemic colitis: infectious or medicamentous colitis? 25 cases].
AB  - The diagnosis of non-gangrenous ischaemic colitis is difficult to assert when
      histological findings are not specific and when no precipitating cardiovascular
      event can be found. The constant absence of relapse after the initial episode
      suggests that an extraneous triggering event is involved. We have studied
      retrospectively 25 cases of spontaneous ischaemic colitis, looking for a non
      haemodynamic triggering event. At the onset of colitis 9 patients had been taking
      non-steroidal anti-inflammatory drugs or antibiotics for 2 weeks or less. In 3
      other patients colitis was associated with Escherichia coli O157:H7 infection.
      Striking clinical, endoscopic and histological similarities exist between
      ischaemic colitis on the one hand and colitis caused by absorption of non
      steroidal anti-inflammatory drugs or ampicillin and the colitis reported in E.
      coli O157:H7 infection on the other hand. Non-steroidal anti-inflammatory drugs
      and E. coli O157:H7 intestinal infection, possibly facilitated by an antibiotic
      treatment with e.g. ampicillin, could be either non-haemodynamic triggering
      factors for ischaemic colitis, or responsible per se for a transient acute
      colitis with the same characteristics as ischaemic colitis.

PMID- 1386433
TI  - [Postmenopausal bone loss. Role of estrogens].
AB  - Menopause is attended by an increase in bone remodelling, predominantly
      resorption, resulting in a trabecular and cortical bone loss which can be
      prevented by administration of oestrogens. This indicates that oestrogen
      deficiency is one of the major physiopathological elements of postmenopausal
      osteoporosis. The mechanism of action of oestrogens has not yet been fully
      elucidated. The recent finding of functional oestrogen receptors in osteoblasts
      suggests that oestrogens might have a direct action on bone cells, side by side
      with their action on the activity or production of calcitropic hormones. The
      antiresorptive effect of oestrogens might be due to the osteoblasts producing one
      or several local factors that modulate the differentiation and/or recruitment of
      osteoclasts. Moreover, animal studies have provided arguments in favour of a
      direct action of oestrogens on bone formation.

PMID- 1386434
TI  - [Contribution of early blood lactic acid assay to the diagnosis of generalized
      epileptic crisis].

PMID- 1386435
TI  - [Severe hyponatremia: possible role of omeprazole].

PMID- 1386436
TI  - [C4 component of the complement: a new indirect marker for the prenatal diagnosis
      of toxoplasmosis].

PMID- 1386437
TI  - [Acute kidney failure revealing mastocytosis].

PMID- 1386438
TI  - [Cerebral nocardiosis].

PMID- 1386439
TI  - [Haemophilus b vaccines].

PMID- 1386440
TI  - [Painful sequelae of Wallenberg's syndrome].
AB  - Twenty-seven out of 45 patients who had Wallenberg's syndrome were re-examined as
      out-patients. Nineteen were complaining of pain on the side opposite to that with
      loss or temperature and pain sensations or trigeminal deficit. The follow-up
      showed that pain was both intense and disabling and its treatment was
      disappointing. The most striking finding was the high frequency of painful
      sequelae to Wallenberg's syndrome, since they affected almost one out of two
      patients. The occurrence of these painful symptoms, usually after lesion of the
      spinothalamic tract, is difficult to explain.

PMID- 1386441
TI  - [Mental disorders in elderly hospitalized patients. Epidemiological study in an
      internal medicine department].
AB  - This epidemiological transversal study conducted on 100 patients older than 65
      years hospitalized in the Internal Medicine department of a University hospital
      demonstrates the frequency of psychiatric pathology in these patients: dementia
      19 percent; other psycho-organic disorders 17 percent; affective disorders 23
      percent and other psychological disturbances 4 percent. Thus, 63 percent of this
      patient population had a mental disorder as defined by the DSM III criteria.
      These disorders are generally not or imperfectly identified by the internists in
      charge of these patients.

PMID- 1386442
TI  - [Castleman's disease. An intrapulmonary isolated form with fissural
      exteriorization].
AB  - We report a well-documented case of Castleman's disease which embodied all the
      main features of its localized forms, those most frequently described in the
      literature. This case was particular by its unusual intrapulmonary location and
      its intra-fissural development, which explains why the diagnosis was not
      considered preoperatively. A review of the literature showed that beside the
      localized forms of Castleman's disease multifocal forms have recently been
      reported; these have a much poorer prognosis, and their treatment has not yet
      been established.

PMID- 1386444
TI  - [Pneumocystis carinii infection. Two cases responsible for maternal death during
      pregnancy].

PMID- 1386443
TI  - [Myocardial thallium scintigraphy after administration of dipyridamole.
      Application to the diagnosis and evaluation of coronary insufficiency].
AB  - Myocardial thallium scintigraphy performed after intravenous injection of
      dipyridamole is a non-invasive method to diagnose and evaluate coronary disease.
      It can be used as an alternative to postexercise scintigraphy, both methods
      having similar sensitivity and specificity. The dipyridamole test is
      contraindicated in patients with a history of bronchospasm and uncontrolled
      angina pectoris. Close clinical and electrocardiographic monitoring is required.
      The wide use of tomographic techniques has notably improved this examination.

PMID- 1386445
TI  - [Association of nephrotic syndrome and spondylo-epiphyseal dysplasia].

PMID- 1386446
TI  - [Aeromonas hydrophila infection in a case of open fracture].

PMID- 1386447
TI  - [Value of C-reactive protein assay for the monitoring of the course of treated
      multiple myeloma].

PMID- 1386448
TI  - [Hydatid cyst of the liver disclosed by metastatic subcutaneous localization].

PMID- 1386449
TI  - [Kidney transplantation without cyclosporin in 1991. Results over 3 years].

PMID- 1386450
TI  - [Treatment of severe idiopathic thrombocytopenic purpura with high dose of
      methylprednisolone].

PMID- 1386451
TI  - [A classic, not to be forgotten complication of venous puncture at the bend of
      the elbow: arteriovenous fistula].

PMID- 1386452
TI  - [Malignant renovascular hypertension and unilateral obstruction of the renal
      artery. Value of emergency percutaneous renal angioplasty].

PMID- 1386453
TI  - [Surgery of the abdominal cavity. A technical advance to be applied with
      caution].

PMID- 1386454
TI  - [Visceral leishmaniasis. Diagnosis by western blotting].
AB  - Using Western blotting, antibodies directed against a 94 kiloDalton Leishmania
      antigen are detectable in the sera of patients with visceral leishmaniasis. The
      absence of these antibodies in the sera of patients with other leishmaniasis,
      protozoiases, helminthiases, and fungal or bacterial diseases, makes it a
      biological marker of visceral leishmaniasis, and gives this method its value in
      immunodiagnosis.

PMID- 1386455
TI  - [Silent exercise-induced enzymatic myopathies at rest in adults. A cause of
      confusion with fibromyalgia].
AB  - Exercise-induced enzymatic myopathies include carnitine palmityl transferase
      deficiency and, among muscular glycogenoses, Mac Ardle's and Tarui diseases.
      These diseases are usually recognized when exercise-induced myalgias,
      myoglobinuria and raised creatinine kinase (CK) levels are present. However,
      myoglobinuria may be absent in 10 to 50 percent of the cases, and CK levels are
      often normal at rest; thus, the diagnosis is often delayed for several years,
      with a risk of acute renal failure in 10 to 30 percent of the patients. We report
      6 cases of exercise-induced enzymatic myopathies with normal CK levels and with
      electromyographic studies at rest. The main clinical features of these cases and
      those of similar conditions reported in the literature are male sex, onset of the
      disease before the age of 15 years, episodes of severe exercise-induced myalgias,
      cramps and muscle weakness and myogenic hyperuricaemia at rest in muscular
      glycogenosis.

PMID- 1386456
TI  - [Ischemic cerebral vascular stroke after heroin sniffing. A new case].
AB  - Three hours after sniffing a dose of heroin, a 30-year old man developed right
      hemiplegia with aphasia. Magnetic resonance imaging of the brain showed an
      infarct in the territory of the left anterior choroid artery. Cerebral vascular
      accidents occurring as complications of heroin addiction are rare: a review of
      the literature yielded only 13 documented cases. The main characteristics of
      these strokes are analysed and their pathogenetic mechanisms (immuno-allergic
      vasculitis, vascular spasm) are discussed.

PMID- 1386457
TI  - [Apolipoprotein C-III in nephrology].
AB  - Apolipoprotein C-III is synthesized by the liver and the small intestine. It
      inhibits the actions of lipoprotein lipase and hepatic triglyceride lipase. An
      increase of plasma apolipoprotein C-III levels has been found in patients with
      renal failure, in those under haemodialysis and in renal transplant recipients.
      The consequences of this increase correlate with the hypertriglyceridaemia
      observed in these patients. The responsibility of hormonal or non-hormonal
      factors that modulate the metabolism of apolipoprotein C-III is discussed in
      order to help in the understanding of the physiopathological mechanisms of lipid
      disorders in these renal diseases.

PMID- 1386459
TI  - [Accessory spleen localized in the gastric wall].

PMID- 1386458
TI  - [Postmenopausal bone loss. Role of progesterone and androgens].
AB  - Oestrogen deficiency is the main physiopathological factor of postmenopausal
      osteoporosis. The repercussions on bone metabolism of decrease in other sex
      steroid levels (progesterone, androgens) remains imperfectly known. Several
      studies on both animals and man have demonstrated that androgens and progestogens
      derived from testosterone have an anabolic effect on bone tissue. The latest data
      from studies conducted in non-menopausal women treated with progesterone suggest
      that this hormone might prevent bone loss. The mechanism of action of this effect
      on cells remain to be determined, even though progesterone has been shown to
      exert a mitogenic activity in vitro. Altogether, these data suggest that side by
      side with oestrogen deficiency the decrease of other sex steroid levels might
      also play a role in the physiopathology of postmenopausal bone loss.

PMID- 1386460
TI  - [Necrosis of the first part of the duodenum after endoscopic, then surgical
      treatment of a hemorrhagic ulcer of the bulb].

PMID- 1386461
TI  - [Diphetarsone-induced hepatitis. A second case].

PMID- 1386462
TI  - [Late gastric metastasis of cancer of the kidney].

PMID- 1386463
TI  - [Asthma caused by hard metals: responsibility of titanium].

PMID- 1386464
TI  - [Primary lymphoma of the thyroid: terminology, diagnostic criteria and
      relationship to Hashimoto's thyroiditis].

PMID- 1386465
TI  - Prevention of hyperglycemia improves the long-term result of islet
      transplantation in streptozotocin-diabetic rats.
AB  - We examined the hypothesis that prevention of hyperglycemia during the critical
      period immediately following islet transplantation will improve the outcome of
      the transplantation in streptozotocin-diabetic rats. Two days after intravenous
      injection of streptozotocin (70 mg/kg), 400 or 1,000 islets were transplanted
      into the left kidney subcapsular space. A group of rats transplanted with 400
      islets was treated with insulin from 1 day before transplantation and for 7 days.
      Intravenous glucose infusion was performed at 10 days and 3 months after
      transplantation. In addition, at 3 months, the grafts were examined by light and
      electron microscopy. We found that rats transplanted with 400 islets without any
      concomitant insulin administration remained diabetic throughout the 3-month
      period and no plasma insulin response was induced by glucose infusion in these
      rats. In contrast, diabetic rats transplanted with 400 islets and treated with
      insulin for 7 days remained normoglycemic throughout the 3-month period, as did
      rats transplanted with 1,000 islets. Furthermore, these rats had normal glucose
      stimulated insulin secretion both at 10 days and at 3 months after
      transplantation. Moreover, islet grafts from rats transplanted with 400 islets
      and administered insulin as well as from rats transplanted with 1,000 islets were
      morphologically normal, and following removal of the graft, hyperglycemia
      developed rapidly. In contrast, the islet grafts from rats transplanted with 400
      islets without concomitant insulin administration had only few insulin cells.
      Thus, by preventing hyperglycemia at the time of islet transplantation, the long
      term result of islet transplantation was improved. Therefore, the ambient glucose
      level initially following islet transplantation is critical for the long-term
      result.

PMID- 1386466
TI  - Intracerebroventricular administration of a specific IL-1 receptor antagonist
      blocks food and water intake suppression induced by interleukin-1 beta.
AB  - Intracerebroventricular (ICV) microinfusion of recombinant human interleukin-1
      beta (rhIL-1 beta, 1.0 ng/rat) suppressed the short-term (2 h) food and water
      intakes in rats. ICV infusion of recombinant human IL-1 receptor antagonist (rhIL
      1ra) had no effect on food or water intake. Concomitant ICV infusion of rhIL-1
      beta (1.0 ng/rat) and increasing concentrations of rhIL-1ra (25 to 1000 ng/rat)
      resulted in a dose-dependent inhibition of the short-term food and water intake
      suppression induced by rhIL-1 beta. The highest doses of rhIL-1ra (500 and 1000
      ng/rat) completely blocked the food and water intake suppression induced by rhIL
      1 beta. This suggests specificity of IL-1 beta suppression of short-term feeding
      and drinking by a direct action in the central nervous system (CNS). This ability
      of rhIL-1ra may have potential therapeutic implications in acute and chronic
      pathological processes associated with increased levels of IL-1 and appetite
      suppression.

PMID- 1386467
TI  - Effects of dexamethasone on the development of radiation nephropathy in the rat.
AB  - Low-dose, chronic administration of the synthetic glucocorticoid, dexamethasone,
      to male CD-I rats in the drinking water or by osmotic minipumps implanted
      subcutaneously after supralethal irradiation of the kidneys (20 Gy) was studied.
      The effectiveness of treatment with dexamethasone in the drinking water at
      concentrations of 23 micrograms/l to 188 micrograms/l and treatment times varying
      from 33 to 166 days was evaluated. At monthly intervals kidney function was
      assayed by measuring the clearance of 51Cr-ethylenediaminetetraacetic acid. All
      dexamethasone treatment regimens increased survival times significantly and
      delayed the development of kidney dysfunction. The most effective combination of
      concentration of dexamethasone in drinking water and treatment interval after
      irradiation with respect to survival was 94 micrograms/l and 88 days. However, a
      slightly longer survival and a better functional result was obtained if an
      equivalent amount of dexamethasone was administered by minipumps. Shielding the
      adrenal glands during kidney irradiation did not prolong survival. This shows
      that the beneficial effect of dexamethasone is not due to compensation for
      reduced adrenal glucocorticoid production resulting from concomitant exposures of
      these glands during kidney irradiation.

PMID- 1386468
TI  - Vascular response to fractionated irradiation in the rat lung.
AB  - The effects of fractionated hemithorax irradiation on normal lung tissue were
      examined by measuring changes in the vascular permeability surface area product
      (PS) and relative lung blood flow in Sprague-Dawley rats. The rats received five
      daily fractions per week of either 3.0 or 4.0 Gy for 4 weeks to the left lung.
      Between 3 and 5 weeks after the start of irradiation, the average PS was
      approximately 50% above normal for the group of rats that received 3.0 Gy/day and
      200-300% above normal in the group of rats that received 4.0 Gy/day. Treatment
      with cyproheptadine, indomethacin, or theophylline had no effect, but treatment
      with dexamethasone significantly reduced PS to near normal levels. Left-to-right
      blood flow ratios in the group of rats that received 3.0 Gy/day decreased to 66%
      of normal levels by 4 weeks. In the group of rats that received 4.0 Gy/day, blood
      flow decreased to 46% of normal levels by 4 weeks. Treatment with dexamethasone
      maintained normal blood flow until the drug dose was reduced. These results agree
      with earlier studies using single-dose irradiation and indicate that the methods
      used to measure PS and blood flow are sensitive at low doses.

PMID- 1386469
TI  - Impact of chronic illness in children on parental living conditions. A population
      based study in a Swedish primary care district.
AB  - In a geographically defined child population aged 0-15, every twelfth child
      suffered from chronic illness. Their parents and randomly selected control
      children's parents were asked about their living conditions using questionnaires.
      Non-responders (30%) had the same sociodemographic profile as responders. The
      socioeconomic level in index families (n = 95) was lower than in control families
      (n = 166). Both parents worked fewer hours in index than in control families.
      Index mothers had more health problems and sick days than control mothers. The
      parents' social relations were most hampered by having children with allergic
      disorders or mental retardation. Despite reduced hours, more absence from work to
      care for sick children, and reduced leisure activities, two thirds of the parents
      of moderately/severely disabled children found it difficult to cater adequately
      to the needs of their child. A family approach is recommended to provide
      comprehensive care of children with chronic illness, in which both specialized
      and primary care are needed.

PMID- 1386470
TI  - Photodynamic therapy for thoracic malignancies.
AB  - Photodynamic therapy (PDT) is an experimental form of cancer therapy which
      employs photoactivation of a sensitizing chemical by light of a given wavelength
      via the production of toxic oxygen species. PDT causes local destruction of
      cancer, and relies on a therapeutic index between normal and malignant tissue
      since the latter seems to selectively retain the sensitizer. PDT has both direct
      tumoricidal effects as well as indirect effects on tumor vasculature causing an
      early hemorrhagic necrosis of tissue. The treatment has been used for the
      treatment of endobronchial obstruction by primary and metastatic tumors. Most
      recently, trials are being performed to evaluate this therapy as a surgical
      adjunct in the treatment of pleural malignancies such as mesothelioma.

PMID- 1386471
TI  - Preactivation: a new concept for generation of photoproducts for potential
      therapeutic applications.
AB  - Controlled exposure of photoactive compounds to light prior to their use in
      biological targets results in the formation of heretofore unknown photoproducts.
      This process of photoproduct generation, termed preactivation, renders the
      photoactive compound capable of systemic use without further dependence on light.
      We have demonstrated that preactivated Merocyanine and preactivated Photofrin-II
      possess significant antitumor and antiviral activity against certain tumor cells
      and viruses, while under identical conditions normal cells and tissues are
      minimally affected. Thus, the preactivation procedure may represent a promising
      therapeutic modality for controlling systemic malignancies and viral infections.

PMID- 1386472
TI  - The relationship between verbal ability and sentence-based speechreading.
AB  - Eighteen hearing-impaired subjects participated in the present study. The purpose
      was to investigate one general question: The nature of the relationship between
      verbal ability and speechreading. Verbal ability was assessed by two types of
      measure: a test of vocabulary size, and four tests of lexical access speed. The
      results demonstrated that lexical access speed was related to speechreading
      performance. Vocabulary size was not found to be directly related to the
      speechreading criterion; rather, its influence was in an indirect fashion via its
      relation to lexical access speed. It was concluded that lexical access speed
      could be used as a diagnostic tool, such that when an individual demonstrates
      lexical access that is unreasonably slow, it could be taken as an indication to
      suggest that rehabilitation programs should emphasize alternatives to
      speechreading. A general implication of the present results is that absence of
      relation between a predictor variable and the speechreading criterion does not
      necessarily imply absence of relation between the two. There is still a
      possibility that the predictor variable might be indirectly related to the
      speechreading criterion.

PMID- 1386474
TI  - Hepatitis B virus infection among Swedish adults: aspects on seroepidemiology,
      transmission, and vaccine response.

PMID- 1386473
TI  - White blood cells in infants with congenital toxoplasmosis: transient appearance
      of cALL antigen on reactive marrow lymphocytes.
AB  - Existing serological methods for diagnosing congenital toxoplasmosis are
      inadequate. We have therefore characterized the features of peripheral blood cell
      counts and smears in a prospective study of 8 affected infants during their first
      year of life. Enlarged, vacuolated lymphocytes were observed in all patients. Six
      patients had periods of neutropenia; in 1 patient the neutropenia was severe and
      prolonged. A bone marrow aspirate from this patient showed enhanced myelopoiesis,
      and after stimulation with hydrocortisone, but not with adrenaline, his
      neutrophil count normalized. Phenotyping of his bone marrow cells revealed that
      approximately 55% of both the immature and mature B lymphocytes were positive for
      the cALL antigen. Of the 8 patients, 6 had mild eosinophilia, 4 had mild
      monocytosis and 3 had increased numbers of plasma cells in the peripheral blood.
      These findings may reflect the activity of the congenital toxoplasma infection
      and may thus contribute to the diagnosis, particularly in patients with silent
      serology.

PMID- 1386475
TI  - [Peak flow profile and expert testimony. The significance of peakflow self
      assessment for pneumological expert testimony].
AB  - Quantitative assessment of pulmonary obstructive diseases, such as asthma, may be
      difficult because of variability of obstruction. This is particularly true with
      regard to expert evidence pulmonary physicians deliver to insurances. Severity of
      obstruction, degree of impairment by an obstructive ventilatory defect, and
      temporal relationship of bronchial obstruction to exposure, may not be detected
      by physiological measurements in the pulmonary function laboratory. Much of the
      expert's opinion on these matters will depend on the credibility he assigns to
      the insured individual. The insured individual, in the other hand, has no other
      proof available than the description of his complaints, which puts him at a
      disadvantage. Serial peak flow measurements can be instrumental in clarifying
      such issues. They add an objective dimension to the case history. Six cases in
      which expert evidence was commissioned by insurances are described in detail, to
      exemplify how the thinking of the experts was modified by peak flow profiles. The
      greater usefulness of serial peak flow measurements in occupational asthma is
      emphasized and problems that may arise with peak flow measurements are discussed.

PMID- 1386476
TI  - Access to ambulatory care among noninstitutionalized, activity-limited persons 65
      and over.
AB  - This study examined the impact of income and insurance type on ambulatory care
      contact use by persons 65 and over who expressed a limitation in their activity.
      This large group (39% of noninstitutionalized older persons in 1984) had
      significantly more health problems and ambulatory care contacts than persons not
      activity-limited. The only previous study on equity in use of physician services
      among elderly in poorer than average health found relatively little inequality of
      use due to income and insurance. This study came to the opposite conclusion.
      Activity-limited persons without Medicare private supplementary insurance, as
      well as those with supplementary insurance in the bottom and middle of the income
      distribution, had 15-32% fewer ambulatory care contacts than activity-limited
      persons with higher income and private supplementary insurance. Particularly
      striking were the declines in consumption among middle income persons relative to
      the reference group, indicating that the issue of equity in consumption of health
      services among older disabled persons affects a much broader group than only the
      poor and near-poor.

PMID- 1386477
TI  - [Atrial natriuretic peptide. Mechanisms of its action].
AB  - A survey of the mechanisms of stimulation of secretion and of atrial natriuretic
      peptide (ANP) and its action is presented. Action of this hormone is particularly
      important on the kidney, the cardiovascular system and on some endocrine tissues.
      Major secretory organs are atrial myocytes, with an increased intra-atrial
      pressure as the stimulus. Under the action of ANP occurs dilatation of arterial
      blood vessels, often masked in vivo by a secondary increase in the sympathetic
      tone. ANP decreases the venous return with consecutive lowering of cardiac
      output. In a kidney an increase in diuresis and natriuresis occurs. Among the
      actions on the endocrine tissues inhibition of aldosterone secretion and, most
      probably, inhibition of renin secretion, are the most important.

PMID- 1386478
TI  - Recombinant interleukin-1 receptor antagonist (IL-1ra): effective therapy against
      gram-negative sepsis in rats.
AB  - BACKGROUND: Morbidity and mortality from bacterial sepsis remain high despite
      aggressive diagnostic and therapeutic intervention. Interleukin-1 has been
      implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis.
      The current experiments were designed to evaluate the therapeutic efficacy of a
      human recombinant interleukin-1 receptor antagonist (IL-1ra) against
      polymicrobial gram-negative septicemia in rats. METHODS: Male rats underwent
      placement of indwelling carotid arterial and superior vena caval catheters
      followed by cecal ligation and puncture (CLP). After 3 hours rats received either
      IL-1ra (10 mg/kg intravenous bolus followed by 5 mg/kg/hr) or an equal volume of
      vehicle intravenously for 24 hours. Heart rate, respirations, mean arterial blood
      pressure, and temperature were recorded at frequent intervals, and survival was
      assessed for 30 hours after CLP. RESULTS: There were no differences in vital
      signs between groups at baseline or before treatment, and all animals appeared
      ill with huddled posture, piloerection, and hyperventilation. Twenty-four hours
      after CLP, IL-1ra significantly ameliorated bradycardia (p = 0.01), hypothermia
      (p = 0.001), and hypotension (p = 0.05), and 30-hour survival was significantly
      improved (71% vs 20%, p less than 0.05). CONCLUSIONS: IL-1ra lessens the acute
      hemodynamic, hypothermic, and mortal effects of gram-negative sepsis induced by
      CLP in rats. These data suggest that IL-1 receptor blockade may be an important
      new treatment strategy against overwhelming bacterial sepsis.

PMID- 1386479
TI  - Up-regulation of prolactin gene expression and feedback modulation of lymphocyte
      proliferation during acute allograft rejection.
AB  - BACKGROUND: Although recent evidence suggests that prolactin is important in the
      immune response, bidirectional communication between prolactin and the immune
      system has not been demonstrated previously. We examined our hypothesis that this
      communication exists during mouse skin allograft rejection. METHODS: Serum
      prolactin levels were measured by bioassay, and pituitary prolactin mRNA was
      examined by use of Northern blots, in BALB/c mice receiving skin allografts from
      C57BL mice, on days 2, 4, and 6 after grafting. The feedback effects of prolactin
      on splenic lymphocytes were assessed in one-way mixed lymphocyte reactions, with
      or without added interleukin-2 (IL-2) or IL-4. RESULTS: Prolactin mRNA was
      increased significantly in grafted animals compared with sham animals (2.4-fold
      by day 4). Serum prolactin bioactivity was also elevated on all days tested.
      Prolactin treatment resulted in dose-dependent modulation of the mixed lymphocyte
      reaction with lymphocytes from grafted animals but not from sham animals. These
      effects depended on the time points and the presence of IL-2 or IL-4; the maximal
      enhancement occurred with day-4 lymphocytes cultured with IL-4 (80%).
      CONCLUSIONS: This report is the first to implicate in vivo immune regulation of
      prolactin gene expression. Our observations indicate that bidirectional
      interaction exists between prolactin and the immune system and provide a
      rationale for altering prolactin levels to treat allograft rejection.

PMID- 1386481
TI  - Declining popularity of laparoscopic tubectomy, why?

PMID- 1386480
TI  - Effects of microsomal enzyme inducers upon UDP-glucuronic acid concentration and
      UDP-glucuronosyltransferase activity in the rat intestine and liver.
AB  - This study was conducted to evaluate UDP-glucuronosyl-transferase (UDP-GT)
      activity, UDP-glucuronic acid (UDP-GA) concentration, and UDP-glucose (UDPG)
      concentration in the rat intestine and liver following oral administration of
      butylated hydroxyanisole (BHA), benzo[a]pyrene (BaP), 3-methylcholanthrene (3MC),
      phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), or trans-stilbene oxide (TSO). Microsomal UDP
      GT activity was assayed in vitro with acetaminophen (AA), harmol (HA), and 1
      naphthol (NA) as the aglycones. Intestinal HA and AA glucuronidation were
      enhanced by BHA, BaP, and TSO, whereas 3MC, PB, PCN, and TCDD augmented hepatic
      HA-glucuronide formation and BHA, PB, PCN, TCDD, and TSO significantly increased
      hepatic AA glucuronidation. All inducing agents except PB and PCN markedly
      increased both intestinal and hepatic NA glucuronidation. PB, PCN, and TCDD
      paradoxically decreased intestinal glucuronidation of AA and HA. A similar effect
      upon hepatic glucuronidation was not observed with any of the agents studied.
      Hepatic UDP-GA concentration was increased significantly by all inducers studied
      except PCN and TCDD, whereas hepatic UDPG concentration was increased only by
      BHA. In the intestine, significant increases in UDP-GA concentration were
      produced only by BHA and BaP, which also elevated intestinal UDPG. These results
      demonstrate that microsomal enzyme inducers evoke different effects upon
      intestinal and hepatic glucuronidation. These differences are manifested with
      regard to induced changes in UDP-GT activity as well as treatment-induced
      alterations in UDP-GA content. Thus, the present study further underscores the
      marked variance of intestinal and hepatic xenobiotic glucuronidation.

PMID- 1386482
TI  - Abdominal drain insertion using Sergent's intestinal depressor.

PMID- 1386483
TI  - Evaluation of a monoclonal blocking ELISA and IHA for antibodies to Mycoplasma
      hyopneumoniae in SPF-pig herds.
AB  - A monoclonal blocking enzyme-linked immunosorbent assay (ELISA) and an indirect
      haemagglutination assay (IHA) were applied to serum samples from 124 specific
      pathogen-free (SPF) breeding and multiplying herds, which participate in the
      routine serological surveillance of the Danish SPF programme. Clinical and
      pathological observations of the herds and microbiological culturing of
      Mycoplasma hyopneumoniae were used to calculate herd sensitivity, herd
      specificity and herd predictive values for the two serological assays. The ELISA
      was superior to the IHA in herd sensitivity and herd specificity, with values of
      93 per cent and 96 per cent, respectively, for the ELISA, and 61 per cent and 92
      per cent for the IHA. During the six month period of evaluation 2.5 per cent of
      the herds were infected with M hyopneumoniae each month. At this level the IHA
      was found to have a positive herd predictive value of 16 per cent, compared with
      39 per cent for the ELISA. The negative herd-predictive value on the same level
      was 99.8 per cent for the ELISA and 98.9 per cent for the IHA. If the assays were
      applied to a group of herds with a herd prevalence of M hyopneumoniae infection
      of 30 per cent (as is the case with the production herds in the Danish SPF
      programme) the predictive value of a positive herd diagnosis would be 91 per cent
      for the ELISA and 76 per cent for the IHA, and the predictive value of a negative
      herd diagnosis would be 97 per cent with the ELISA and 85 per cent with the
      IHA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386484
TI  - Nuclear and nucleolar targeting signals of Semliki Forest virus nonstructural
      protein nsP2.
AB  - Semliki Forest virus nonstructural protein nsP2, when expressed in the absence of
      other viral proteins, is transported into the nucleus, with a specific enrichment
      in nucleoli. This implies that information for its nuclear targeting must be in
      nsP2 itself. To define the nuclear and nucleolar targeting signals of nsP2, a
      series of in-frame deletions were made in its coding sequence. We have identified
      one amino-terminal (residues 25-110) and another carboxy-terminal (residues 634
      661) deletion, both of which rendered nsP2 cytoplasmic. The carboxy-terminal
      region had a pentapeptide sequence P 648R RRV, which resembles some of the known
      nuclear localization signals. When the three arginines were substituted with
      aspartic acids, the mutant nsP2 was localized in the cytoplasm. Especially
      arginines 648-649 were shown to be critical. The carboxy-terminal 232 amino acid
      residues of nsP2 were able to translocate beta-galactosidase to the nucleus as a
      fusion protein, whereas the amino-terminal 110 residues failed to do so. Studies
      with different beta-galactosidase-nsP2 fusions showed that the pentapeptide is
      necessary for nuclear transport but that its activity is strongly affected by the
      context. The deletion analysis indicated also that the nuclear localization
      signal was not sufficient for nucleolar targeting of nsP2. The nucleolar
      targeting sequence of nsP2 was tentatively mapped between residues 470 and 539,
      and at least residues 470-489 are an essential part of it.

PMID- 1386486
TI  - The effects of medroxyprogesterone acetate and ethinylestradiol on hemogram,
      prostate, testes, and semen quality in normal dogs.
AB  - Three dogs were treated with medroxyprogesterone acetate (MPA) and three were
      treated with ethinylestradiol. The results indicate that at a dosage of 3-4.8
      mg/kg b.w. MPA does not have any detrimental effects on hemogram, testicles or
      semen quality, whereas ethinylestradiol (2 micrograms/kg b.w./day) can negatively
      affect both testes and semen quality. Both drugs can cause a decrease in
      prostatic size in clinically healthy dogs. Measurements of peripheral serum
      testosterone levels indicate that at the dosages used, testosterone levels are
      depressed considerably more by ethinylestradiol than by MPA.

PMID- 1386485
TI  - Factors underlying spontaneous inactivation and susceptibility to neutralization
      of human immunodeficiency virus.
AB  - To determine the factors governing inactivation and neutralization, physical,
      chemical, and biological assays were performed on a molecular clone of human
      immunodeficiency type 1 (HIV-1HXB3). This included quantitative electron
      microscopy, gp120 and p24 enzyme-linked immunosorbent assays, reverse,
      transcriptase assays, and quantitative infectivity assays. For freshly harvested
      stocks, the ratio of infectious to noninfectious viral particles ranged from 10(
      4) to 10(-7) in viral stocks containing 10(9) to 10(10) physical particles per
      milliliter. There were relatively few gp120 knobs per HIV particle, mean
      approximately 10 when averaged over the total particle count. Each HIV particle
      contained a mean approximately 5 x 10(-17) g of p24 and approximately 2 x 10(-16)
      g of RNA polymerase, corresponding to about 1200 and 80 molecules, respectively.
      The spontaneous shedding of gp120 envelope proteins from virions was exponential,
      with a half-life approximately 30 hr. The loss of RNA polymerase activity in
      virons was also exponential, with a half-life approximately 40 hr. The physical
      breakup of virions and the dissolution of p24 core proteins were slow (half-life
      greater than 100 hr) compared to the gp120 shedding and polymerase loss rates.
      The decay of HIV-1 infectivity was found to obey superimposed single- and
      multihit kinetics. At short preincubation times, the loss of infectivity
      correlated with spontaneous shedding of gp120 from virions. At longer times, an
      accelerating decay rate indicated that HIV requires a minimal number of gp120
      molecules for efficient infection of CD4+ cells. The blocking activity of
      recombinant soluble CD4 (sCD4) and phosphonoformate (foscarnet) varied with the
      number of gp120 molecules and number of active RNA polymerase molecules per
      virion, respectively. These results demonstrate that the physical state of
      virions greatly influences infectivity and neutralization. The knowledge gained
      from these findings will improve the reliability of in vitro assays, enhance the
      study of wild-type strains, and facilitate the evaluation of potential HIV
      therapeutics and vaccines.

PMID- 1386487
TI  - Spontaneous in vitro megakaryocyte colony formation in primary thrombocythemia:
      relation to platelet factor 4 plasma level and beta-thromboglobulin/platelet
      factor 4 ratio.
AB  - Seventeen patients with primary thrombocythemia (PT) were evaluated for in vitro
      bone marrow megakaryocyte progenitors (CFU-MK) using a plasma clot system. The
      aim of this study was to find out whether spontaneous growth of CFU-MK could be
      used in the diagnosis of PT. The number of CFU-MK was normal in 7 patients and
      reduced in 10 patients. In the absence of stimulating factor, CFU-MK grew
      spontaneously in 12 patients, while in 5 patients no spontaneous CFU-MK were
      observed. The mean plasma level of platelet factor 4 (PF4) was significantly
      higher (p less than 0.05) in patients without spontaneous CFU-MK (59.8 +/- 59.6
      IU/ml; mean +/- SD) compared to patients with (18.1 +/- 20.7 UI/ml). The mean
      plasma level of beta-thromboglobulin did not differ between patients with or
      without spontaneous CFU-MK. The beta-thromboglobulin/PF4 ratio was significantly
      higher (p less than 0.01) in patients with spontaneous CFU-MK (9.9 +/- 7.1)
      compared to patients without (3.1 +/- 1.4). These results suggest that PF4 could
      inhibit in vitro spontaneous growth of CFU-MK.

PMID- 1386489
TI  - Results of directional atherectomy of primary atheromatous and restenosis lesions
      in coronary arteries and saphenous vein grafts.
AB  - Directional coronary atherectomy (DCA) was performed in 158 patients over a 2
      year period at the Mayo Clinic. Primary atheromatous lesions were treated in 92
      patients (group 1) and restenosis lesions were treated in 66 (group 2). Technical
      success (recovery of tissue and greater than or equal to 40% luminal enlargement
      with a residual stenosis of less than 50%) was achieved in 152 lesions (92%);
      clinical success (technical success and no in-hospital death, Q-wave myocardial
      infarction or coronary bypass surgery) was achieved in 143 patients (91%).
      Adjunctive balloon angioplasty was used in 41 patients. DCA was successful less
      often in group 1 than in group 2 (86 vs 97%; p = 0.038). A major complication
      occurred in 7% of patients; in-hospital death, Q-wave myocardial infarction and
      emergency coronary bypass surgery occurred in 3, 1 and 4% of patients,
      respectively. Major complications were more frequent in group 1 than in group 2
      (10 vs 1; p = 0.02). During a follow-up period of 14 +/- 8 months, no difference
      between the groups was found in the incidence of late death (4%), Q-wave
      myocardial infarction (1%), recurrent severe angina (29%), bypass surgery (15%)
      or repeat interventional procedure of the same vascular segment (24%). Vein graft
      and restenosis lesions tended to have greater success and fewer complications.
      Angiographic restenosis (increase of greater than or equal to 30% in stenosis
      severity by visual assessment) occurred in 62% of patients and 58% of lesions
      with successful DCA, and was similar in the 2 groups; a tendency toward higher
      restenosis rates was seen in patients with vein graft DCA.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1386488
TI  - Establishment of the primary structure of the major lipid-dependent Ca2+ binding
      proteins of chicken growth plate cartilage matrix vesicles: identity with
      anchorin CII (annexin V) and annexin II.
AB  - Electron microscopic studies of calcifying vertebrate tissues reveal the locus of
      de novo mineral formation within matrix vesicles (MV). The direct involvement of
      MV in the initiation of mineral formation is supported by the fact that MV
      isolated from avian growth plate cartilage rapidly accumulate large amounts of
      Ca2+ and P(i) and induce mineral formation. Exploration of the constituents of MV
      has revealed two major protein components, a 33 and a 36 kD protein, the former
      of which binds to cartilage-specific collagens. These annexin-like proteins bind
      to acidic phospholipids in the presence of submicromolar levels of Ca2+.
      Antibodies raised against both the purified 33 and the 36 kD MV annexin do not
      cross-react with the other, indicating that they are distinct proteins. Reported
      here are studies elucidating the primary structure of both MV proteins using both
      conventional protein and molecular biologic methods. These studies establish that
      the 33 kD protein is nearly identical to anchorin CII (annexin V) and that the 36
      kD protein is identical to avian annexin II. Immunolocalization studies show that
      hypertrophic chondrocytes at the calcification front of avian growth plate
      contain the highest level of these annexins. Further, immunogold labeling
      indicates that the annexins are localized within MV isolated from the growth
      plate. Recent studies indicate that annexin V is a new type of ion-selective Ca2+
      channel protein that possesses selective collagen binding properties. Since MV
      are tightly associated with the collagen- and proteoglycan-rich matrix, it is
      tempting to speculate that this MV protein may be a component of stretch
      activated ion channels that enhance Ca2+ uptake during mechanical stress.

PMID- 1386490
TI  - Relation of regression of left ventricular hypertrophy to changes in ambulatory
      blood pressure after long-term therapy with perindopril versus nifedipine.
AB  - Casual as well as ambulatory 24-hour blood pressure (BP) and echocardiographic
      parameters were studied in 40 patients with untreated or insufficiently treated
      mild to moderate essential hypertension. Left ventricular (LV) hypertrophy was
      assessed before and after 24 weeks of therapy with either the converting enzyme
      inhibitor perindopril or the calcium antagonist nifedipine. The design was a
      double-blind parallel study with a placebo run-in period. Patients received a
      daily oral dosage of either 4 to 8 mg of perindopril or 40 to 80 mg of nifedipine
      in slow-release form. A diuretic (25 mg/day of hydrochlorothiazide) was added in
      nonresponders (greater than 90 mm Hg casual diastolic BP). Once-daily perindopril
      and twice-daily nifedipine comparably reduced both casual and ambulatory BP
      throughout 24 hours (p less than 0.01) without affecting 24-hour heart rate. Six
      subjects withdrew from the nifedipine group and 4 from the perindopril group.
      After 12 and 24 weeks of therapy, LV hypertrophy was significantly reduced by
      both agents. Before active treatment was begun, LV mass index was more closely
      correlated to 24-hour (p less than 0.001) than to casual BP. This correlation
      disappeared after treatment with both agents. The correlation between ambulatory
      systolic day-time BP and LV mass was only still present (r = 0.54; p less than
      0.05) after 24 weeks of treatment with nifedipine. It is concluded that
      regression of LV hypertrophy during converting enzyme inhibition or calcium
      antagonism may be partly independent of dosage and magnitude of 24-hour BP
      decrease.

PMID- 1386491
TI  - Effectiveness of endopeptidase inhibition (candoxatril) in congestive heart
      failure.
AB  - Candoxatril is a novel, orally active inhibitor of neutral endopeptidase EC
      3.4.24.11, the enzyme that degrades atrial natriuretic peptide (ANP). The acute
      and chronic (10 days treatment) hemodynamic and hormonal effects of candoxatril
      (150 mg twice daily) in 12 patients with moderately severe congestive heart
      failure were investigated in a randomized, placebo-controlled, double-blind
      study. On study day 1, candoxatril acutely increased plasma ANP levels,
      suppressed aldosterone and decreased right atrial and pulmonary capillary wedge
      pressures. After 10 days of treatment, basal ANP was increased and basal
      aldosterone was decreased. Body weight was reduced, most likely reflecting
      chronic natriuretic or diuretic effects, or both, and there was a trend toward
      increased cardiac index and reduced preload values. On study day 10, the acute
      effects of candoxatril were similar to those on day 1 (i.e., ANP was further
      increased, aldosterone was suppressed, and right and left ventricular filling
      pressures were decreased). Thus, candoxatril may offer a new and effective
      therapeutic approach in the treatment of heart failure.

PMID- 1386493
TI  - Changes in plasma concentrations of atrial natriuretic peptides after
      cardioversion of chronic atrial fibrillation.

PMID- 1386492
TI  - Measurement of coronary and peripheral artery flow by intravascular ultrasound
      and pulsed Doppler velocimetry.

PMID- 1386494
TI  - Immunohistochemical study of T cell receptor gamma delta cells in chronic liver
      disease.
AB  - The distribution and phenotypic characterization of T cell receptor (TCR) gamma
      delta cells in human liver tissue was investigated immunohistochemically at light
      and electron microscopic levels. In chronic liver disease, there was a
      significant increase in the number of TCR gamma delta cells and in the percentage
      of TCR gamma delta cells to CD3+ cells in the portal areas and hepatic sinusoids.
      Hepatic TCR gamma delta cells were classified as small or large gamma delta
      cells. Large gamma delta cells were increased in chronic liver disease, whereas
      both small and large gamma delta cells were increased in the portal areas and
      hepatic sinusoids in liver cirrhosis. The increased TCR gamma delta cells were of
      the BB3+ (peripheral) type, indicating that TCR gamma delta cells in the liver
      were of the same lineage as those in the peripheral blood. In addition, the
      majority of the TCR gamma delta cells in the portal areas of liver cirrhosis
      patients were CD4- and CD8- (double negative). Immunoelectron microscopy showed
      that the large gamma delta cells were lymphoblastoid and contained multivesicles.
      The present study clearly demonstrated that there are two types of TCR gamma
      delta cells, and that these cells were significantly increased in the livers of
      patients with chronic liver disease. This suggests that they may be involved in
      regulation of the immune response and hepatocellular damage in chronic liver
      disease.

PMID- 1386495
TI  - A recombination event that redefines the Huntington disease region.
AB  - We report both a recombination event that places the Huntington disease gene
      proximal to the marker D4S98 and an extended linkage-disequilibrium study that
      uses this marker and confirms the existence of disequilibrium between it and the
      HD locus. We also report the cloning of other sequences in the region around
      D4S98, including a new polymorphic marker R10 and conserved sequences that
      identify a gene in the region of interest.

PMID- 1386496
TI  - Human tritanopia associated with a third amino acid substitution in the blue
      sensitive visual pigment.

PMID- 1386497
TI  - Growth hormone subnormality in Down syndrome.

PMID- 1386498
TI  - Halothane and isoflurane effects on Ca2+ fluxes of isolated myocardial
      sarcoplasmic reticulum.
AB  - To elucidate better the differential myocardial depressant actions of halogenated
      volatile anesthetics, anesthetic-induced changes in Ca2+ accumulation, release,
      and Ca-ATPase (Ca2+ pump) activity of isolated canine cardiac sarcoplasmic
      reticulum (SR) vesicles were examined. An initial crude microsomal fraction of
      homogenized canine ventricle was subfractionated on a discontinuous sucrose
      gradient after Ca2+ loading in the presence of phosphate. Junctional SR (JSR)
      enriched with terminal cisternae was identified by its content of an
      electrophoretically verified approximately 450-kDa protein, the Ca(2+)-release
      channel (CaRC). When the CaRC of JSR was blocked by 1 microM ruthenium red (RR),
      the rate of Ca2+ uptake increased 47% as measured spectrophotometrically using
      the Ca-sensitive dye antipyrylazo III. A second fraction was identified as
      primarily longitudinal SR (LSR) based on its trace content of 450-kDa protein and
      11% increase of Ca2+ uptake with RR. Halothane (0.75-2.5%) or isoflurane (2.5-4%)
      decreased net Ca2+ accumulation rate by either LSR or JSR, and the decrease in
      uptake rate of JSR was only partially reversed by addition of 1 microM RR (27%
      increase for isoflurane, 7% increase for halothane). Both halothane and
      isoflurane increased JSR ATP consumption as measured by a coupled-enzyme assay.
      45Ca2+ efflux from passively loaded SR vesicles was then determined to verify
      that the decreased net uptake rate was due to enhanced Ca2+ efflux from vesicles.
      Both anesthetics increased passive Ca2+ efflux from SR vesicles in which the CaRC
      was blocked by 10 microM RR as well as those in which Ca2+ release via the CaRC
      was activated by 10 microM Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386499
TI  - Intensive analgesia reduces postoperative myocardial ischemia? I.

PMID- 1386501
TI  - Quantitation of T-cell receptor V beta chain expression on lymphocytes from
      blood, brain, and spinal fluid in patients with multiple sclerosis and other
      neurological diseases.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central
      nervous system in which large numbers of T cells enter the brain and
      cerebrospinal fluid (CSF). To determine whether these cells represent restricted
      populations, we studied expression of T-cell receptor V beta chains on paired
      samples from the central nervous system and blood of patients with MS or other
      neurological diseases (OND) using a quantitative polymerase chain reaction. The
      distribution of V beta chain expression in blood was skewed, with a significant
      preponderance of message from V beta genes 1 through 8 (p = 0.0001). Such skewing
      was not present in samples from the CSF and brain. Patterns of V beta gene
      expression were different among paired samples from spinal fluid and blood and
      were relatively heterogeneous. Blood and CSF samples from a patient with acute
      meningitis were studied on two separate occasions. The patterns of V beta
      expression changed over 72 hours in both the blood and the CSF. With one
      exception, no oligoclonal populations of T cells were observed nor were there
      disease-specific patterns of V beta gene expression in the blood or CSF. Samples
      from 2 MS brains and 1 OND brain expressed patterns of V beta genes that were
      different and less heterogeneous than those in paired blood. In addition,
      expression of V beta 12 was remarkably increased in the 2 MS brains, suggesting a
      selective recruitment or expansion of T cells expressing this gene. These data
      demonstrate that populations of T cells from blood, spinal fluid, and brain
      differ from one another and can fluctuate during periods of acute
      inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386500
TI  - Functional heredity protein S deficiency with arterial thrombosis.
AB  - Protein S is a vitamin K-dependent protein that functions as a regulatory protein
      to limit clotting. The authors present and discuss the case of a 37-year-old man
      with a type IIa protein S deficiency. The diagnosis and treatment of a protein S
      deficiency is also described.

PMID- 1386502
TI  - [Reproducibility of the measurement of humeral artery diameter, velocity of
      carotido-femoral pulse wave and digital pulse wave in normal subjects].
AB  - The aim of this study was to assess the intra-observer reproducibility at short
      and medium term of three non-invasive methods of arterial measurement: in the
      same day eight volunteers underwent five successive measurements of brachial
      artery diameter by two dimensional pulsed Doppler of the carotido-femoral pulse
      wave velocity by a piezoelectric transducer. The measurements were repeated three
      times at two weeks' interval. The short term (same day) and medium term (after
      several weeks) reproducibility of the first two methods of measurement was good:
      4.69 +/- 2.37%/4.24 +/- 1.90% and 4.09 +/- 1.16%/5.02 +/- 1.71% respectively for
      brachial artery diameter and carotido-femoral pulse wave velocity. The
      reproducibility of the method of measuring digital pulse wave velocity was 10.64
      +/- 3.50%/11.62 +/- 4.25%, confirming the greater variability of this parameter.
      Our results with these noninvasive techniques indicate that they may be used to
      study the arterial system and could be clinically useful in the surveillance of
      hypertensive patients.

PMID- 1386503
TI  - [Atrial natriuretic factor and cardiac insufficiency].
AB  - The atrial natriuretic factor (ANF) is a vasodilating and natriuretic peptide. In
      experimental and human cardiac failure, plasma ANF concentrations are increased.
      The ANF is a good marker of functional and haemodynamic severity and of the
      prognosis of cardiac failure. In this syndrome, messenger RNA of ANF is expressed
      not only in the atria but also in the ventricles which also secrete the peptide.
      Attenuation of the natriuretic response is observed in cardiac failure. It may be
      related to an abnormality situated after the receptor and second messenger,
      cyclic GMP and/or the reduction of renal perfusion pressure which occurs in
      cardiac failure. The therapeutic perspectives of ANF in cardiac failure are
      limited by the necessity of continuous intravenous or parenteral administration.
      Inhibitors of the enzyme degrading the peptide, neutral endopeptidase, are under
      evaluation in clinical trials which are at a preliminary stage for the moment.

PMID- 1386504
TI  - Laparoscopic cholecystectomy and other procedures.

PMID- 1386505
TI  - Laparoscopic cholecystectomy. The new 'gold standard'?
AB  - Laparoscopic cholecystectomy has rapidly been adopted by surgeons, but concerns
      remain about its safety, the management of common bile duct stones, and the means
      of appropriate training. Of 647 patients referred for cholecystectomy,
      preoperative endoscopic retrograde cholangiography was performed in 49 (7.6%),
      with 27 patients (4%) undergoing sphincterotomy and stone extraction. Traditional
      cholecystectomy was performed in 29 patients (4.5%). Laparoscopic cholecystectomy
      was attempted in 618 patients and completed successfully in 600 (97.1%). Surgical
      trainees functioned as the primary surgeon in 70% of cases. Technical
      complications occurred in three patients (0.5%), including one patient with a
      common bile duct laceration (0.2%). Major complications occurred in 10 patients
      (1.6%), with no perioperative mortality. Mean postoperative hospital stay was 1
      day, with return to work or full activity a mean of 8 days after surgery. Two
      cases of retained common bile duct stones (0.3%) were identified. We now regard
      laparoscopic cholecystectomy as the "gold standard" therapy for management of
      symptomatic cholelithiasis.

PMID- 1386506
TI  - Intraperitoneal carbon dioxide insufflation and cardiopulmonary functions.
      Laparoscopic cholecystectomy in pigs.
AB  - We studied the effects of laparoscopic cholecystectomy on respiratory and
      hemodynamic function in eight adult pigs. Minute ventilation was adjusted to
      normalize baseline arterial blood gases, then fixed throughout carbon dioxide
      insufflation. A metabolic measurement cart recorded total CO2 excretion, oxygen
      consumption, and minute ventilation. Carbon dioxide pneumoperitoneum was
      maintained at a constant pressure of 15 mm Hg as cholecystectomy was performed.
      After 1 hour of insufflation, CO2 excretion increased from 115 +/- 10 mL/min to
      149 +/- 9 mL/min but O2 consumption remained unchanged. The PaCO2 increased from
      35 +/- 2 mm Hg to 49 +/- 3 mm Hg and arterial pH fell from 7.47 +/- 0.02 to 7.35
      +/- 0.03. Systemic and pulmonary hypertension occurred and stroke volume dropped
      from 35.5 +/- 3.5 mL to 28.6 +/- 2.2 mL with compensatory tachycardia. Right
      atrial pressure remained unchanged as inferior vena cava pressure increased to
      reflect the intraperitoneal pressure. We conclude that CO2 pneumoperitoneum
      resulted in significant transperitoneal CO2 absorption, with secondary
      hypercapnia and acidemia. The accumulation of CO2 was also associated with an
      increase in systemic and pulmonary arterial pressure. Heart rate increased to
      compensate for the decreased stroke volume to maintain cardiac output.

PMID- 1386507
TI  - Management of infrainguinal occluded vein bypasses with a combined approach of
      thrombolysis and surveillance. A prospective study.
AB  - Intra-arterial thrombolysis with urokinase was attempted on 23 occluded
      infrainguinal vein bypasses. Lesions revealed by thrombolysis included 11
      anastomotic stenoses, five midbypass stenoses, five native artery stenoses, and
      five unusable diffusely stenotic vein conduits. Adjunctive procedures performed
      immediately after successful thrombolysis included 10 local surgical revisions,
      five balloon angioplasties, and five new vein bypasses. Three nonanastomotic vein
      bypass stenoses and two common iliac artery stenoses were detected using a
      surveillance protocol in subsequent follow-up of patients with patent bypasses.
      Twelve-month patency following thrombolysis (including immediate failures) was
      52.4%. The use of thrombolysis in the management of occluded vein bypasses allows
      the identification and correction of pathological lesions. Once revised,
      continued vein bypass patency may be improved with a surveillance program.

PMID- 1386508
TI  - Laparoscopic pelvic lymph node dissection for carcinoma of the prostate and
      bladder.
AB  - Improvements in instruments and camera systems have allowed the development of
      operative techniques for laparoscopic pelvic lymph node dissection. A series of
      dissections in 20 patients is reported. The mean operation time was 1 h and 40
      min. When the nodes appeared malignant, a node biopsy was sent for frozen
      section. If this was positive, the dissection went no further. In three patients
      it was necessary to complete the operation by open surgery. A mean number of five
      lymph nodes was dissected per side. After laparoscopic dissection, all patients
      were discharged the morning after surgery. The operation is possible without
      making great demands on hospital bed occupancy and the patient has a comfortable
      and speedy return to normal activity. Using laparoscopic techniques, node
      dissection becomes a more appealing option as an investigation and staging
      procedure.

PMID- 1386509
TI  - Laparoscopic removal of a detached peritoneal shunt catheter with revision of
      ventriculo-peritoneal shunt.

PMID- 1386510
TI  - Inhibition of rat peroxisomal palmitoyl-CoA ligase by xenobiotic carboxylic
      acids.
AB  - ATP-dependent coenzyme A (CoA) ligases catalyse the formation of the acyl-CoA
      thioesters of xenobiotic carboxylic acids and the formation of xenobiotic-CoAs
      has been implicated as being a causative factor in peroxisomal proliferation. In
      this study we have demonstrated using rat liver peroxisomes that the formation of
      palmitoyl-CoA is inhibited by a variety of xenobiotic carboxylic acids. Palmitoyl
      CoA formation exhibited biphasic kinetics indicative of two isoforms, a high
      affinity (Km1 2.3 microM) low capacity form and a low affinity (Km2 831 microM)
      high capacity form. These forms were differentially inhibited by a range of
      xenobiotics. However, it would appear that the low affinity component may not
      contribute to any major extent to the formation of xenobiotic-CoAs in vivo. At a
      concentration of 1 mM, greater than 20% inhibition of the high affinity form was
      observed with the 2-arylpropionates, ibuprofen, naproxen, benoxaprofen,
      fenoprofen, indoprofen, ketoprofen, tiaprofenic acid and cicloprofen, the
      hypolipidaemics, nafenopin and ciprofibrate, and the herbicides, silvex and 2,4,5
      trichlorophenoxyacetate. Valproic acid, clofibric acid, salicylic acid and 2,4
      dichlorophenoxy-acetate were non-inhibitory at all concentrations studied (0.1
      2.5 mM). Analysis of the type of inhibition established that only nafenopin (Ki
      430 microM) and ciprofibrate (Ki 97 microM) were competitive inhibitors of
      palmitoyl-CoA formation suggesting that they bind at the active site and thus
      potentially function as alternative substrates for the peroxisomal ligase.
      Notably, clofibric acid which has previously been shown to form clofibroyl-CoA in
      peroxisomes did not interact with the palmitoyl-CoA ligase thereby suggesting
      that activation is mediated via an alternative peroxisomal CoA ligase. In
      addition, the xenobiotic inhibitors of the peroxisomal palmitoyl-CoA ligase
      differed from those previously reported for the equivalent microsomal enzyme
      suggesting that the organellar forms may be functionally distinct. This study
      establishes that numerous xenobiotic carboxylic acids interact with the
      peroxisomal palmitoyl-CoA ligase; however, it would appear that relatively few
      function as alternative substrates. The toxicological ramifications of
      peroxisomally mediated xenobiotic-CoA formation and the identification of other
      peroxisomal xenobiotic-CoA ligase(s) remain to be elucidated.

PMID- 1386511
TI  - Studies on the structure of the ligand-binding site of the brain D1 dopamine
      receptor.
AB  - A series of group-specific modifying reagents were tested for their effects on
      [3H]SCH23390 binding to brain D1 dopamine receptors in order to identify amino
      acid residues at the ligand binding site of the D1 dopamine receptor that are
      critical for ligand binding. The dependence of ligand binding on the pH of the
      incubation medium was also examined. The histidine-selective reagent,
      diethylpyrocarbonate did affect ligand binding but this is probably not due to an
      effect at the ligand binding site. Experiments with N-acetylimidazole and
      ethylacetimidate indicated that modification of tyrosine and amino residues did
      not exert major influences at the ligand binding site. The use of the thiol
      dithiothreitol indicated that breakage of a disulphide bond altered ligand
      binding, probably by affecting the receptor conformation, and the use of the
      sulphydryl reagent 5,5'-dithio-bis-nitrobenzoic acid showed that modification of
      a sulphydryl group on the receptor inhibited ligand binding. The carboxyl reagent
      N,N'-dicyclohexyl carbodiimide (DCCD) potently inhibited ligand binding and the
      effect could be prevented by occupancy of the receptor site by an agonist or
      antagonist so that there is an important carboxyl group at the receptor binding
      site. The total number of D1 receptors was reduced after the modification by DCCD
      and 70% of the residual receptors showed a reduced affinity for binding
      [3H]SCH23390, the remainder having the same affinity as untreated receptors.
      [3H]SCH23390 binding is also reduced by a decrease of pH and this effect seems to
      depend on the protonation of a group of pKa 6.9. Saturation analysis of
      [3H]SCH23390 binding performed at pH 7.5 shows a single class of high affinity
      sites whereas at pH 6.0, two classes of sites with higher and lower affinities
      are seen. These studies suggested a model whereby [3H]SCH23390 binding is to two
      receptor isoforms with different pH dependencies for [3H]SCH23390 binding.

PMID- 1386512
TI  - Soybean trypsin inhibitor and beta-amylase induce alveolar macrophages to release
      nitrogen oxides.
AB  - Rat alveolar macrophages incubated with soybean trypsin inhibitor and beta
      amylase produced nitrite in a dose- and time-dependent manner. This production
      depends on the presence of L-arginine (L-arg) in the culture medium. The
      precursor of this nitrite was demonstrated as being nitric oxide by bleaching
      ferredoxin at 410 nm when added to the culture medium. NG-Monomethyl-L-arginine
      and the tetrahydrobiopterin biosynthesis inhibitor 2,4-diamino-6
      hydroxypyrimidine inhibited the release of nitrite in a dose-dependent manner.
      Dexamethasone was able to modulate this release. These data indicate that
      alveolar macrophages are capable of secreting L-arg-derived nitrogen oxides when
      stimulated with certain alimentary proteins.

PMID- 1386513
TI  - Role of gamma/delta T cells in rheumatoid inflammation.

PMID- 1386514
TI  - [Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of
      controlled clinical studies].
AB  - In the first part the statistical methods of meta-analysis are discussed. Meta
      analysis is considered as a statistical tool for quantitatively summarizing the
      results of clinical trials with comparable aims (treatments) and designs. Meta
      analysis can be based on the significance probabilities or effect values. The
      last procedure is preferable as it gives an estimate (and confidence interval)
      for the global effect of the treatment of interest, if homogeneity of the effects
      between the trials can be assumed. Such a homogeneity can be often achieved by a
      suitable standardization of the effect variables within the trials. In the second
      part the methods of meta-analysis are applied to controlled clinical trials with
      Ginkgo biloba extract EGb 761 in patients with peripheral arterial disease.
      Included were 5 placebo-controlled clinical trials with similar design and
      inclusion criteria. In all studies treatment effect was quantified by the
      increase of walking distance (measured in standardized treadmill exercise). The
      effect value of EGb 761 treatment was expressed by the standardized mean
      difference in walking distance increase between EGb 761 and placebo, standardized
      by the standard deviation. It could be shown that this effect value is
      homogeneous in all trials. The global effect size was estimated as 0.75. This
      means that the mean increase in walking distance achieved by EGb 761 is 0.75
      times of the standard deviation higher than that achieved by placebo. This value
      is highly significant different from zero. So the meta-analysis revealed a highly
      significant therapeutic effect of EGb 761 for the treatment of peripheral
      arterial disease.

PMID- 1386515
TI  - Phosphodiesterase inhibition by enoximone in preparations from nonfailing and
      failing human hearts.
AB  - The effects of enoximone (MDL 17043, Perfan, CAS 77671-31-9) on the activities of
      the phosphodiesterase (PDE) isoenzymes I-IV and on force of contraction were
      investigated in ventricular preparations isolated from failing (end-stage
      myocardial failure, NYHA IV) and non-failing human hearts. In both tissues four
      PDE isoenzymes (PDE I-IV) with similar properties were separated by DEAE
      sepharose chromatography. The effects of enoximone on PDE I-IV activities did not
      differ between non-failing and failing human hearts. As compared to PDE I (IC50
      2100 mumol/l) and II (IC50 2900 mumol/l) enoximone is a selective PDE III (cGMP
      inhibited PDE, IC50 5.9 mumol/l) and PDE IV (cGMP-insensitive PDE, IC50 21.1
      mumol/l) inhibitor. Milrinone, 3-isobutyl-1-methylxanthine (IBMX) and UD-CG 212
      Cl, a derivative of pimobendan, were studied in the failing heart for comparison.
      Milrinone inhibited PDE I-IV activities similar to enoximone, revealing IC50
      values for inhibition of PDE III and IV (1.2 and 3.3 mumol/l) which were about
      two orders of magnitude lower than that of PDE I and II (173 and 306 mumol/l). UD
      CG 212 Cl was the most potent (IC50 0.05 mumol/l) and most selective PDE III
      inhibitor tested (IC50 for PDE I, II and IV were 175, 181 and 40.8 mumol/l,
      resp.), whereas IBMX inhibited PDE I-IV nonselectively (IC50 15.3, 26.2, 5.6, 5.8
      mumol/l, respectively). In trabeculae carneae from nonfailing and failing human
      hearts enoximone increased force of contraction only marginally by 18.0 +/- 9.1%
      (n = 8) and 24.5 +/- 8.7% (n = 9) of the predrug value.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1386516
TI  - A molecular model of MHC class-I-restricted antigen processing.
AB  - Cells of higher vertebrates have evolved mechanisms that allow a sample of their
      intracellular contents to be available for surveillance by the immune system.
      This display of intracellular material is in the form of peptides bound to cell
      surface major histocompatibility complex (MHC) class I molecules. In this review,
      John Monaco presents a model of the mechanisms by which this takes place, based
      on the recent identification of a number of new genes in the MHC.

PMID- 1386517
TI  - [The T-lymphocyte antigen receptor].
AB  - The precise knowledge of the T-cells antigen receptor (TCR) is of paramount
      importance; it is the first structure involved in the antigen (allergen)
      recognition, provided this one is presented in the right conditions; that is in
      the context of HLA molecules present at the surface of macrophages, after being
      processed inside. The TCR alpha/beta, present on more than 90% of peripheral T
      cells, is formed of two glyco-protein chains of similar molecular weight. The
      cytoplasmic end of the TCR is two short to transmit the message of recognition.
      The signal is transduced by neighbouring molecules forming the CD3 complex. Other
      membrane proteins such as CD2, LFA1, reinforce adhesion between immuno-competent
      cells. The presence or absence of CD4 or CD8 surface antigens, permit to
      distinguish two T cell subpopulations, namely helper and suppressor/cytotoxic
      lymphocytes. The TCR gene organization is very similar to that of light and heavy
      chains of immunoglobulins. Their fortuitous rearrangement explains the very large
      diversity of the T-cell repertoire. The TCR gamma/delta, although first appeared
      on the thymic cells, is present on less than 5% of peripheral lymphocytes, where
      its exact role is still unknown.

PMID- 1386518
TI  - [Cytokines and allergy].
AB  - The immune system is a homeostatic system adaptating the internal self to the
      variations of the external non-self and allowing us to get on well together with
      the environment. Intercellular communications are necessary for the system well
      operating and are mediated by either direct contacts or by soluble factors called
      cytokines. Allergy is the upshot of a disregulation of the immune response that
      does not discriminate between a potentially harmful antigen (tetanus toxoid) and
      a rather harmless antigen (pigeon droppings). This could be the result of an
      imbalance between two helper T lymphocytes subsets called TH1 and TH2: their main
      produced cytokines, respectively IFN-gamma and IL-4, have opposite effects on IgE
      synthesis whereas other cytokines (IL-3, IL-5) are more directly involved in the
      differentiation of eosinophil and mast cells lineages.

PMID- 1386519
TI  - Observations, legends, and conjectures concerning restricted T-cell receptor
      usage and autoimmune disease.
AB  - It has become clear over the past few years that a variety of experimental
      autoimmune conditions are mediated by T cells bearing a highly restricted subset
      of antigen receptors. This restricted TcR usage raises important questions
      concerning not only the recognition of autoantigens, but also the pathogenic
      mechanisms underlying many models of autoimmunity. Furthermore, the extension of
      these findings in certain cases to human disease has raised the possibility of
      specific therapeutic immune intervention. In this review, we examine the
      available data on restricted T-cell receptor usage in autoimmune disorders and
      explore the interpretations and the theoretical and practical implications of
      these findings.

PMID- 1386520
TI  - Hepatitis B immunization: vaccine types, efficacy, and indications for
      immunization.

PMID- 1386521
TI  - Muscle pathology in idiopathic cricopharyngeal dysphagia. Enzyme histochemical
      and electron microscopic findings.
AB  - The structural changes in the cricopharyngeal muscle (CM) were examined
      ultrastructurally and by enzyme histochemistry in five patients suffering from
      idiopathic cricopharyngeal dysphagia (ICD). Diagnosis was established by
      fiberoptic esophagoscopy, esophageal manometry and cineradiography.
      Cricopharyngeal myotomy was performed with marked improvement in all patients.
      Intraoperatively, a biopsy was taken from the CM. Additionally, all patients
      underwent neurological examination for possible generalized muscle disease, and a
      biopsy was taken from a limb muscle. CM from nine cadavers without known history
      of dysphagia served as control. The control samples disclosed structural changes
      which were considered to be pathological in other skeletal muscles, and required
      that the criteria for CM pathology we modified accordingly. In three patients
      changes in CM histology suggested specific pathogenesis: one patient had evidence
      for a generalized myositis but was only symptomatic for dysphagia. Another
      patient had muscle fiber atrophy and slight inflammation in her CM, possibly due
      to alcohol abuse. The third patient had loss of CM fibers with replacement by
      connective tissue enough to cause functional disturbances. In two patients no
      cause for dysphagia was found in either immunohistochemistry or electron
      microscopic studies. These results demonstrate the special structural features of
      the CM and indicate that ICD can have multiple etiologies.

PMID- 1386522
TI  - Uptake of sufentanil, alfentanil and morphine in the lungs of patients about to
      undergo coronary artery surgery.
AB  - We have studied the pulmonary extraction and retention of sufentanil, alfentanil
      and morphine using a double indicator technique in 30 patients undergoing
      elective aortocoronary bypass surgery. Patients were allocated to three groups
      (10 each) to receive sufentanil 43 micrograms, alfentanil 672 micrograms or
      morphine 1887 micrograms, mixed with indocyanine green as indicator. After
      sufentanil, mean peak extraction was 93.7% (95% confidence interval 87.1-100.4%)
      and release occurred after 16.1 (13.8-18.4) s; first-pass retention was 61.1
      (51.3-70.9)%. After alfentanil, peak extraction was 67.4 (42.7-92.0)% and release
      occurred after 9.9 (8.5-11.3) s; first-pass retention was 10.1 (3.5-16.7)%. After
      morphine, peak extraction was 58.3 (44.4-72.2)% and release occurred after 7.2
      (4.4-10.1) s; first-pass retention was 7.1 (-4.7-19.9)%. Both peak extraction and
      first-pass retention were significantly greater after sufentanil. There was no
      significant difference in the peak extraction and first-pass retention between
      alfentanil and morphine.

PMID- 1386524
TI  - vav: a molecule for all haemopoiesis?

PMID- 1386523
TI  - Efficacy of orally administered ondansetron in the prevention of postoperative
      nausea and vomiting: a dose ranging study.
AB  - In a placebo-controlled, double-blind study, we have compared the efficacy of
      ondansetron 16 mg, 8 mg and 1 mg administered 8-hourly for prevention of
      postoperative nausea and vomiting. We studied 995 patients undergoing major
      gynaecological surgery; 982 were included in the analysis. Study medication was
      administered 1 h before induction of anaesthesia and second and third doses were
      given 8 and 16 h after the first. The treatment groups were similar for patient
      characteristics, surgical procedures, anaesthetics administered and opioids
      given. The frequency of nausea was 75%, 70%, 56% and 55% after placebo and
      ondansetron 1 mg, 8 mg and 16 mg, respectively; the corresponding frequencies of
      vomiting were 60%, 55%, 37% and 37%. Ondansetron 8 mg was as effective as 16 mg
      and both resulted in significant reductions in nausea and vomiting compared with
      placebo and ondansetron 1 mg (P less than 0.001).

PMID- 1386525
TI  - Abnormal CD45R expression in patients with common variable immunodeficiency and X
      linked agammaglobulinaemia.
AB  - This study has investigated the patterns of membrane 2H4 (CD45RA) and UCHL1
      (CD45RO) expression by CD4+ and CD8+ lymphocyte subpopulations in 10 adults and
      seven children with common variable immunodeficiency (CVI) and X-linked
      hypogammaglobulinaemia (XLA). Of the 10 adults (CVI, n = 8; XLA, n = 2), only one
      with a diagnosis of CVI showed normal CD45R expression. For the remaining seven
      adult CVI patients the abnormal CD45R profiles were primarily associated with
      CD4+ lymphocytes in three and CD8+ lymphocytes in four. Specific increases in
      CD45RA- CD45RO+ fractions were found in four CVI patients and in all of these
      there was a concomitant reduction in circulating CD19+ B-cell numbers. Two of the
      CVI cases were identical twin sisters and both had the same CD45R abnormality.
      The two adults with XLA also showed abnormal CD45R expression (increased CD45RA+
      CD45RO- components) but of particular note, in view of the fact that these were
      brothers, one was associated with the CD4+ subpopulation and the other with the
      CD8+ fraction. Similar analyses for the paediatric group revealed, in distinct
      contrast to the adult patients, no significant abnormalities of CD45R expression
      suggesting that these defects may not become apparent until a later age. Further
      investigations of in vitro lymphocyte proliferation (PHA and PWM) in the eight
      adults with CVI showed a significant correlation between abnormal responses and
      disordered CD45R expression. It is proposed that these abnormal patterns of CD45R
      expression by lymphocyte subpopulations in CVI and XLA may be of fundamental
      importance with respect to the pathogenesis of these particular
      immunodeficiencies.

PMID- 1386526
TI  - Heparin-associated thrombocytopenia in a patient treated with polysulphated
      chondroitin sulphate: evidence for immunological crossreactivity between heparin
      and polysulphated glycosaminoglycan.
AB  - Heparin-associated thrombocytopenia (HAT) type II, a severe side effect of
      heparin therapy, is thought to be induced by an immunological mechanism. By
      crossreactivity studies we have demonstrated that sera of patients with HAT type
      II activate platelets in vitro not only after the addition of heparin but also
      after addition of a chemically polysulphated chondroitin-like substance,
      Arteparon, used for treatment of degenerative joint disease. In addition here, we
      describe a patient who developed deep venous thrombosis and pulmonary embolism
      following administration of Arteparon and typical HAT type II with
      thrombocytopenia, 36 h after the first administration of heparin. This patient
      had never received heparin, but had repeatedly been treated with Arteparon for
      degenerative joint disease. We conclude that this patient had been presensitized
      by Arteparon, as indicated by his clinical course. In vitro studies again confirm
      crossreactivity between heparin and Arteparon.

PMID- 1386527
TI  - Characterization of stable beryllium fluoride, aluminum fluoride, and vanadate
      containing myosin subfragment 1-nucleotide complexes.
AB  - Beryllium and aluminum fluorides are good phosphate analogues. These compounds,
      like orthovanadate, form stable complexes with myosin subfragment 1 (S1) in the
      presence of MgADP. The formation of the stable S1-nucleotide complexes is
      characterized by the loss of ATPase activity. For the complete loss of ATPase
      activity there was necessary a higher concentration of aluminum than of beryllium
      or vanadate. In the presence of MgATP the onset of the inhibition is delayed,
      which indicates that stable complexes cannot form when a specific site is
      occupied by the gamma-phosphate of ATP or by P(i) derived from the gamma
      phosphate. The half-lives of the S1-MgADP-(BeF3-), S1-MgADP-(AlF4-), and S1-MgADP
      Vi complexes at 0 degrees C are 7, 2, and 4 days, respectively. In the presence
      of actin the rate of decomposition of all of the complexes is significantly
      enhanced; however, the order of decomposition is reversed, the fastest rate being
      observed with beryllium and the slowest with aluminum. The formation of the S1
      MgADP-(BeF3-) and S1-MgADP-(AlF4-) complexes is accompanied by an increase in
      tryptophan fluorescence similar to that observed upon addition of MgATP to S1.
      The fluorescence increase develops rather slowly, by suggesting that the rate
      limiting step in the formation of the stable complex is an isomerization. The
      rate of the fluorescence change accompanying the formation of the Be complex is
      faster than that for the Al complex. Addition of vanadate to S1 causes a static
      quenching of the tryptophan fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386528
TI  - Chloride transport of yeast vacuolar membrane vesicles: a study of in vitro
      vacuolar acidification.
AB  - Effects of various solutes on acidification inside the vacuolar membrane vesicles
      of the yeast Saccharomyces cerevisiae were examined. ATP-dependent acidification
      was stimulated by the presence of chloride salts. There was essentially no
      difference in the stimulatory effects of NaCl, KCl, LiCl, and choline chloride.
      The membrane potential across the vacuolar membrane was reduced by the presence
      of Cl- salts. Transport of 36Cl- is driven by the protonmotive force across the
      vacuolar membrane. Kinetic analyses have revealed that the stimulatory effect of
      Cl- on internal acidification depends on two distinct components. One shows
      linear dependency on chloride concentration and is inhibited by 4,4'
      diisothiocyano-2,2'-stilbenedisulphonic acid (DIDS). The other exhibits saturable
      kinetics with an apparent Km for chloride of 15-20 mM. We conclude that the
      vacuolar membrane of yeast is equipped with Cl- transport systems contributing to
      the formation of a chemical gradient of protons across the vacuolar membrane by
      shunting the membrane potential generated by proton translocation.

PMID- 1386529
TI  - Inhibition of mitochondrial F1-ATPase activity by binding of (2-azido-) ADP to a
      slowly exchangeable non-catalytic nucleotide binding site.
AB  - F1-ATPase was treated so that it contained three tightly bound nucleotides per
      molecule. One of these was bound at a catalytic site and was rapidly
      exchangeable, the two remaining nucleotides were nonexchangeable. Incubation of
      this preparation with ADP in the presence of Mg2+ results in 40-45% inhibition of
      the ATPase activity. With 2-azido-ADP instead of ADP, the ligand was covalently
      bound to F1 by illumination, in the presence or absence of turnover of the
      enzyme, and the site of binding was determined. In this way, one site could be
      identified, which induces the inhibition. The attachment of the covalently bound
      2-nitreno-ADP is at Tyr-368 of a beta-subunit, characterized in the literature as
      a non-catalytic site. A second, non-catalytic site also binds 2-azido-ADP, but
      this binding is partially reversed by the addition of ATP and does not cause
      further inhibition of the ATPase activity. It is concluded that the slowly
      exchangeable non-catalytic site is the site of inhibition by ADP.

PMID- 1386530
TI  - Americans with Disabilities Act. More regulations impacting medical practice this
      month.

PMID- 1386531
TI  - Toxigenic type A Pasteurella multocida as a causative agent of nasal turbinate
      atrophy in swine.
AB  - Although no clinical signs of atrophic rhinitis (AR) were recognized in 2- and 5
      week-old pigs, approximately 60% of 2- to 6-month-old pigs showed clinical signs
      of AR in an affected pig farm. None of the pigs had normal turbinate at
      slaughter. Bordetella bronchiseptica was not isolated from any of the pigs before
      onset and incipient stage of the outbreak (2-week to 2-month-old). Pasteurella
      multocida of capsular type D was not isolated from any of those pigs. However,
      toxigenic P. multocida of capsular type A was isolated from a number of the pigs
      immediately before onset and incipient stage of the outbreak. Thirty-six-day-old
      primary specific-pathogen-free pigs were inoculated intranasally with a toxigenic
      type A P. multocida isolated from a 5-week-old pig. Severe nasal turbinate
      atrophy was observed in those pigs which were necropsied at 3 weeks post
      inoculation. This is the first report on outbreak of severe nasal turbinate
      atrophy induced by toxigenic type A P. multocida in Japan.

PMID- 1386532
TI  - Non-cholinergic mechanisms underlying the acute lethal effects of P = S type
      organophosphorus insecticides in rats.
AB  - Intravenous administration of the lethal dose of diazinon or fenthion, P = S type
      organophosphates, to urethan anesthetized rats induced bradycardia and transient
      apnea followed by a decline of blood pressure, and death. We investigated the
      mechanisms of the lethal action of these organophosphates in rats through
      measurements of blood pressure, heart rate, and respiratory pattern. We compared
      their cardiorespiratory effects in the five different conditions under
      anesthesia; 1) normal (without treatment), 2) artificially ventilated, 3)
      vagotomized, 4) atropinized, 5) pithed, vagotomized and atropinized. It was found
      that the administration of 200 mg/kg of fenthion and 100 mg/kg of diazinon,
      caused sudden bradycardia, transient apnea and gradual decline of blood pressure
      in the anesthetized normal rat, and the rat died. The rats in other conditions
      also died except the artificially ventilated rats, in which 400 mg/kg of fenthion
      was administered to cause hypotension and subsequent death. Hypotension was
      observed consistently even after the cardiac effect such as bradycardia was
      eliminated by atropine treatment. In the pithed rats which were further
      vagotomized and atropinized, these organophosphates also caused hypotension.
      These results may indicate that hypotension is the main cause of death which
      resulted from intravenous administration of the P = S types. Hypotension may be
      caused by peripheral cardiovascular effect of the P = S types, which is unrelated
      to cholinergic mechanisms.

PMID- 1386533
TI  - Low order correlations of lipoprotein(a) with other blood lipids and with
      coagulation and fibrinolysis parameters in hypertensive and diabetic patients.
AB  - Lipoprotein(a) (Lp(a)) has been established as an important independent risk
      factor for the development of cardiovascular disease. Apolipoprotein(a), together
      with apo B-100 the apolipoprotein of Lp(a), is homologeous to plasminogen but
      lacks fibrinolytic capacity and appeared to interfere with fibrinolysis in in
      vitro and ex vivo experiments. We determined the correlations between Lp(a) and
      other blood lipids (serum cholesterol, LDL-cholesterol, HDL-cholesterol,
      triglycerides), coagulation parameters (fibrinogen, factor VII, factor VIII:C
      fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (tissue
      plasminogen activator antigen, plasminogen activator inhibitor-1 and D-dimer) in
      54 patients with essential hypertension, in 65 non-insulin-dependent diabetic
      patients and in 116 insulin-regulated diabetic patients. Signs of activated
      coagulation and increased reactive fibrinolysis were found in all three patient
      groups. In the hypertensive patients, Lp(a) was significantly correlated with LDL
      cholesterol (r = 0.25, P = 0.04) and triglycerides (r = -0.30, P = 0.03), while
      in insulin-regulated diabetics, Lp(a) was also correlated with LDL-cholesterol (r
      = 0.20, P = 0.03). In the hypertensive patients and both diabetic groups there
      was no correlation of Lp(a) with coagulation or fibrinolysis parameters. These
      data show that Lp(a) concentrations are not related to coagulation or
      fibrinolysis parameters in hypertensive or diabetic patients and confirm the
      presence of an activated coagulation system in these patient groups.

PMID- 1386534
TI  - Effect of calmodulin on sarcoplasmic reticulum Ca(2+)-ATPase isolated from
      cardiac muscle.
AB  - A Ca(2+)-dependent ATPase, purified from cardiac microsomal membranes by
      solubilization and chromatography, is identified as cardiac sarcoplasmic
      reticulum ATPase on the basis of its electrophoretic mobility and its trypsin
      digestion pattern. The ATPase (both in membranous and purified form) is
      stimulated by calmodulin, while the skeletal muscle ATPase is not. Rapid kinetic
      experiments demonstrate that the calmodulin stimulation is already present within
      the first enzyme cycle following the addition of ATP, and consists of an
      increased turnover of the phosphorylated enzyme intermediate. The calmodulin
      effect does not involve the phosphorylation of any protein other than the ATPase.
      Following the incubation of ATPase with [gamma-32P]ATP, even in conditions of
      calmodulin stimulation, radioactive phosphorus is found only on the ATPase
      electrophoretic band, corresponding to the phosphorylated enzyme intermediate.
      These observations, together with the results obtained for [125I]calmodulin
      binding to the ATPase, suggest that the stimulation in turnover produced by
      calmodulin on the ATPase is due to a direct effect on the enzyme. This may
      provide an independent regulation of the cardiac sarcoplasmic reticulum Ca(2+)
      ATPase, in addition to the known regulation mediated by other accessory proteins.

PMID- 1386535
TI  - Nucleotide sequence of cDNA clones encoding the beta subunit of mitochondrial ATP
      synthase from the green alga Chlamydomonas reinhardtii: the precursor protein
      encoded by the cDNA contains both an N-terminal presequence and a C-terminal
      extension.
AB  - cDNA and genomic clones encoding the beta subunit of mitochondrial ATP synthase
      from Chlamydomonas reinhardtii have been isolated using heterologous DNA probes
      from the photosynthetic bacterium Rhodospirillum rubrum. The protein encoded by
      the cDNA is 79-83% identical to corresponding proteins from higher-plant and
      mammalian mitochondria, and 75% identical to the R. rubrum protein. It contains
      both an N-terminal presequence and a unique C-terminal extension. The
      presequence, which is the first mitochondrial presequence determined in C.
      reinhardtii, is similar in structure to mitochondrial presequences from other
      organisms. As chloroplast presequences from C. reinhardtii also share features
      with mitochondrial presequences from other organisms (L.-G. Franzen et al., FEBS
      Lett 260 (1990) 165-168), this raises interesting questions about protein
      targeting to chloroplasts and mitochondria in C. reinhardtii. The possibility
      that the C-terminal extension is involved in targeting the protein to the
      mitochondrion is discussed. Southern blot analysis indicates that the protein is
      encoded by a single-copy gene.

PMID- 1386538
TI  - [Diagnosis of chronic backache in health resort patients].
AB  - Conservative treatment of backache requires an accurate diagnosis because
      sometimes such patients are suffering from a serious but unrecognised disease of
      the abdomen or low back region. Diagnoses like cervical syndrome, lumbar syndrome
      or even cervicodorso-lumbar syndrome are not sufficiently conclusive to start
      conservative treatment, since they convey nothing in respect of cause, prognosis
      or aim of treatment. Patients undergoing a course of inpatient curative treatment
      of, say, four weeks in a hospital, need special therapy programmes that are
      meaningfully based on precise data on their disorder. It is important to set
      great store by the physical examination (which is often performed cursorily
      before the patients are referred to curative inpatients treatment), including a
      neurological examination and in some cases also EMG, special radiographs,
      myelography, CT, magnetic resonance imaging and the like to gather more
      information on the real cause of the low back pain. This will also help the
      physician in arriving at a fair estimation of the patient's performance rating. A
      useful classification of patients into two groups would be as follows: a) without
      neurological symptoms, and b) with signs of a nerve-root compression or even
      spinal cord symptoms.

PMID- 1386536
TI  - Developmental and environmental concurrent expression of sunflower dry-seed
      stored low-molecular-weight heat-shock protein and Lea mRNAs.
AB  - We have cloned and sequenced three different cDNAs from sunflower seed-stored
      mRNA. Sequence similarities and response to heat-shock identified one of the
      cDNAs as a low-molecular-weight heat-shock protein (lmw-HSP). The other two
      clones showed significant sequence similarity to the cotton and carrot late
      embryogenesis-abundant (Lea) proteins D-113 and Emb-1, respectively. The three
      cDNAs showed similar expression patterns during zygotic embryo development, as
      well as in vegetative tissues of 3-day-old seedlings in response to stress.
      Maximal accumulation of all three mRNAs was detected in dry seeds and during
      embryo mid-maturation stage, in the absence of exogenous stress. In seedlings,
      mRNAs accumulated to lower levels in response to osmotic stress and exogenous
      abscisic acid (ABA) treatments. A differential time course of response to osmotic
      stress was observed: lmw-HSP mRNA accumulation was induced earlier than that of
      Lea mRNAs. The coordinate accumulation of Lea and lmw-HSP transcripts during
      embryo development and in response to stress and ABA suggests the existence of
      common regulatory elements for Lea and lmw-HSP genes, and supports the notion
      that HSPs might have alternative functions in the plant cell.

PMID- 1386537
TI  - A complete sequence of the rice sucrose synthase-1 (RSs1) gene.
AB  - Using a fragment of the maize sucrose synthase gene Sh-1 as probe, the rice
      genome was shown to contain at least three genes encoding sucrose synthase. One
      of these genes was isolated from a genomic library, and its full sequence,
      including 1.7 kb of 5' flanking sequence and 0.9 kb of 3' flanking sequence, is
      reported. The new rice gene, designated RSs1, is highly homologous to maize Sh-1
      (approx. 94% identity in derived amino acid sequence), and contains an identical
      intron-exon structure (16 exons and 15 introns). Both RSs1 and maize Sh-1 show
      similar sequence homologies to a second rice sucrose synthase gene described
      recently (designated RSs2, Yu et al. (1992) Plant Mol Biol 18: 139-142), although
      both the rice genes predict an extra 6 amino acids at the C-terminus of the
      protein when compared to the maize gene. The RSs1 5' flanking sequence contains a
      number of promoter-like sequences, including putative protein-binding regions
      similar to maize zein genes.

PMID- 1386539
TI  - [Problems of district and workshop health services].

PMID- 1386540
TI  - [Research institutions and their role in the reorganization of Russian health
      services].

PMID- 1386541
TI  - [The health management system].

PMID- 1386543
TI  - Serine/threonine protein kinases.
AB  - Signal transduction in the nervous system is heavily dependent on the three
      multifunctional serine/threonine protein kinases, PKA, PKC, and CaM-KII. Recent
      studies have furthered our understanding of how the multiple isoforms of these
      kinases and their subcellular localizations, regulatory properties, and substrate
      determinants are important for the specificity of kinase functions.

PMID- 1386542
TI  - Use of immobilized metal ions as a negative adsorbent for purification of
      enzymes: application to phosphoglycerate mutase from chicken muscle extract and
      horseradish peroxidase.
AB  - Two enzymes, phosphoglycerate mutase and peroxidase, were purified by using an
      immobilized metal ion adsorbent for the removal of unwanted proteins. The mutase
      was obtained pure from a single column, whereas the purification of peroxidase
      required the use of a thiophilic adsorbent in a tandem. The capacity was 2.5 mg
      pure peroxidase per mL gel.

PMID- 1386544
TI  - The involvement of the intestinal microflora in the expansion of CD4+ T cells
      with a naive phenotype in the periphery.
AB  - It is well known that immune reactivity declines with age. Recently, we
      demonstrated that the age-related decrease in IL-2 production by CD4+ T cells was
      accompanied by an increased production of IL-4 and interferon-gamma (IFN-gamma).
      This age-related shift in the profile of lymphokine production was related to
      phenotypic changes within the CD4+ T-cell subset, that is, a decrease in the
      percentage of CD45RB++ CD4+ T cells and an increase in the percentage of Pgp-1+
      CD4+ T cells. To study whether these age-related changes were due to previous
      antigenic exposure, we performed a phenotypic and functional analysis on splenic
      CD4+ T cells isolated from individual germ-free (GF), specific pathogen-free
      (SPF), and clean conventional (CC) mice. Interestingly, the total number of
      splenic CD4+ T cells in GF mice was twofold lower as compared to age-matched SPF
      or CC mice, regardless whether mice were analyzed at young (10 weeks) or at
      advanced age (13-14 months). Unexpectedly, the phenotypic composition of the CD4+
      T-cell subset was comparable in the GF, SPF, and CC mice as determined by the
      expression of CD45RB and Pgp-1, indicating that CD4+ T cells with a naive
      phenotype (CD45RB++ Pgp-1-) were not enriched in GF mice. Moreover, at an age of
      13-14 months, CD4+ T cells from GF mice frequently produced more IL-4 and IFN
      gamma than their CC counterparts. These lymphokine data showed, therefore, that a
      relatively high proportion of CD4+ T cells with a memory phenotype can also be
      defined in GF mice on the basis of their function. The contamination of GF mice
      with a colonization resistant factor (CRF flora) resulted in twofold higher
      numbers of splenic CD4+ T cells. Surprisingly, not only CD4+ T cells with a
      memory phenotype (CD45RB-/+ Pgp-1++) had expanded, but also CD4+ T cells with a
      naive (CD45RB++ Pgp-1-) phenotype. Our results, therefore, strongly suggest that
      the expansion of naive CD4+ T cells in the periphery is mediated by the
      intestinal microflora.

PMID- 1386545
TI  - Analysis of immature (CD4-CD8-) thymic subsets in T-cell receptor alpha beta
      transgenic mice.
AB  - Introduction of a transgenic alpha beta TCR (V alpha 2, V beta 8.1) specific for
      lymphocytic choriomeningitis virus (LCMV), in the context of H-2Db into the
      genome of C57BL/6 mice, has many effects on the development and selection of T
      cells in both the thymus and the periphery. These mice produce increased numbers
      of CD4-8+ mature T cells, all of which express the transgenic TCR, and small
      numbers of CD4+8- cells using endogenous TCRs are also produced. This study
      follows the intrathymic development of T cells in these TCR alpha beta transgenic
      mice, in particular the earliest CD4-8- stages. As expected, the transgenic TCR
      is expressed on the cell surface at an earlier developmental stage than
      endogenous TCRs in nontransgenic littermate controls. Of the three major subsets
      expressing the heat-stable antigen (HSA), only the most mature, the CD25-CD44-
      expresses the transgenic TCR, and the earlier CD25-CD44+ and CD25+CD44- do not.
      Furthermore, in contrast to other TCR alpha beta transgenic lines, TCR gamma
      delta lineage cells appear to develop normally.

PMID- 1386547
TI  - Lipocortin: what is it and what does it mean?

PMID- 1386546
TI  - Specific activation of platelets from patients allergic to Dermatophagoides
      pteronyssinus by synthetic peptides derived from the allergen Der p I.
AB  - Previous studies have shown that Fc epsilon RII-bearing platelets from patients
      with allergic disorders could be stimulated either by anti-human IgE antibodies
      or the relevant allergens to generate cytotoxic mediators. In this report, the
      reactivity of platelets from Dermatophagoides pteronyssinus (D. pt)-sensitive
      patients to three Der p I-derived synthetic peptides (52-71, 117-133 and 188-199)
      was investigated. The platelet stimulation observed in D. pt-sensitive patients
      was demonstrated to be allergen-specific and to be mediated by IgE. These Der p I
      derived peptides failed to stimulate platelets from healthy donors or platelets
      from non-D. pt-allergic patients. D. pt-sensitive patients responded more
      frequently to the peptides 52-71 and 117-133 than to the peptide 188-199. Thus,
      in this model, synthetic peptides selected for their assumed accessibility on the
      native antigen could be associated to an IgE-dependent biological activity.

PMID- 1386548
TI  - Prognostic factors for radiographic damage and physical disability in early
      rheumatoid arthritis. A prospective follow-up study of 147 patients.
AB  - We studied the influence of demographic, clinical, laboratory and genetic
      features and radiographic damage at onset on the outcome after 2 years in a
      prospective study of 147 patients with classical or definite RA with disease
      duration shorter than 1 year at entry. Outcome was determined by physical
      disability and by radiographic damage of hands and feet. By means of multiple
      regression analysis and discriminant analysis outcome was explained from
      variables at the start and during the first 6 months. No clinically relevant
      conclusions could be made for physical disability due to the low explained
      variance and small number of patients with bad physical disability. Radiographic
      damage after 2 years was predicted by high disease activity at the start
      (measured as erythrocyte sedimentation rate, C-reactive protein or Disease
      Activity Score) combined with DR4 or DR2 (as a prognostically favourable factor)
      and rheumatoid factor positivity. Radiographic damage could be better predicted
      if disease activity during the first 6 months was included. Absence or presence
      of progression of radiographic damage could be correctly predicted in 83% of the
      patients.

PMID- 1386549
TI  - T gamma delta cells and their subsets in blood and synovial fluid from patients
      with rheumatoid arthritis.
AB  - We have determined the distribution of T gamma delta cells in the peripheral
      blood of 44 patients with rheumatoid arthritis and in 36 healthy controls. In
      addition, paired blood and synovial fluid samples were obtained from seven
      patients with RA. The monoclonal antibodies A13, BB3 and Ti gamma A, which are
      specific for the V delta 1, V delta 2 and V gamma 9 gene products respectively,
      were used to define T gamma delta subsets. T gamma delta + cells expressed as a
      percentage of CD3+ lymphocytes were reduced in RA peripheral blood compared with
      the control group (3.9% +/- 0.5 versus 5.7% +/- 0.7; P less than 0.0001). There
      was a reduction in the V gamma 9/V delta 2+ subset (from 5.6% +/- 1.2 to 1.7% +/-
      0.4) leading to a change in the mean ratio of V delta 2/V delta 1+ cells from 4.3
      in normal subjects to 1.1 (P less than 0.002). No statistical difference was
      observed in T gamma delta cell numbers in synovial fluid compared with the paired
      blood samples (4.0% +/- 1.1 in blood and 4.4% +/- 1.4 in synovial fluid). Also
      the distribution of V delta 2+ and V delta 1+ cells was similar in the two
      compartments and a similar alteration in subset distribution was found in blood
      and synovial fluid. These findings do not indicate a selective accumulation of a
      specific T gamma delta subset in RA synovial effusions.

PMID- 1386550
TI  - Heteroconjugated antibodies enhance lymphocyte-mediated tumour cell lysis in
      vitro and in vivo.
AB  - Covalent linkage of an antitumour antibody specific for a tumour cell surface
      antigen to an antilymphocyte antibody specific for the T lymphocyte receptor
      complex produces a heteroconjugated antibody that can activate and redirect
      cytotoxic T lymphocytes to lyse tumour cells. The ability of an antilymphocyte
      antitumour heteroconjugate (500A2 x 96.5) to direct the lysis of murine melanoma
      cells by cultured murine lymphocytes was tested in vitro using a 4-h chromium
      release assay and in vivo with a tumour neutralization assay. In vitro, the
      addition of heteroconjugated antibody significantly increased tumour lysis by
      murine C3H/HeN lymphocytes (median specific lysis 82.7 per cent with lymphocytes
      plus heteroconjugate versus 9.5 per cent for lymphocytes alone, P less than
      0.001). In vivo, treatment with heteroconjugated antibody plus lymphocytes
      significantly reduced the development of pulmonary metastases after intravenous
      tumour administration (median number of pulmonary metastases 28.5 for combined
      treatment versus 250 for heteroconjugate or lymphocytes alone, P less than
      0.001).

PMID- 1386552
TI  - A laparoscopic hazard for the surgeon.

PMID- 1386551
TI  - Retrograde femoral angioplasty: a new technique.

PMID- 1386553
TI  - Cholecystectomy and gallbladder conservation.

PMID- 1386554
TI  - Aggressive arterial reconstruction for critical lower limb ischaemia.

PMID- 1386555
TI  - Effect of anti-CD3 antibody on the generation of interleukin-2-activated
      lymphocytes from tumor tissues of gastrointestinal cancer.
AB  - BACKGROUND: The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy
      using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating
      lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood
      lymphocytes (PBL) was investigated. METHODS: TIL, RLNL, and PBL derived from 39
      patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal
      cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of
      recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was
      added during the initial culture period (day 2 or 4). Cytotoxicity against K562
      cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of
      effector cells generated after culturing for 2-3 weeks were studied. RESULTS:
      Proliferative responses were significantly increased by OKT3 in each type of
      effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than
      PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells
      in OKT3-stimulated groups was significantly larger than that in unstimulated
      groups (P less than 0.01), whereas no differences were observed with CD4+ cells
      (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3
      enhanced the NK-like activity of TIL and PBL but did not affect their LAK
      activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS: OKT3
      stimulation did not significantly enhance the LAK activity, but the authors
      propose that OKT3 could be an effective addition to adoptive immunotherapy using
      TIL due to an increased proliferation and generation of a large cytotoxic T-cell
      population.

PMID- 1386556
TI  - Role of endocrine, autocrine, and paracrine interactions in the development of
      mammary hyperplasia in Wnt-1 transgenic mice.
AB  - The Wnt-1 proto-oncogene is transcriptionally activated by mouse mammary tumor
      virus in mouse mammary tumor virus-induced tumors. Previous studies using
      transgenic mice showed that Wnt-1 expression in mammary gland causes alveolar
      hyperplasias which resemble mammary glands of pregnant mice. To understand the
      role of mammogenic hormones in the genesis of these hyperplasias, we examined the
      development of these glands before puberty in young transgenic mice and the
      effects of ovariectomy and adrenalectomy on the growth and morphology of Wnt-1
      mammary hyperplasia. Mammary glands of Wnt-1 transgenic females showed
      hyperplastic morphology as early as 1 week after birth. The normal structure of
      the uterus of the adult Wnt-1 virgin mouse indicated that the circulating levels
      of ovarian hormones were not elevated. Ovariectomy and adrenalectomy had no
      obvious effect on the morphology of these mammary hyperplasias. To assess
      possible paracrine stimulation of mammary epithelial cells (MEC) by stromal
      cells, we transplanted MEC from normal BALB/c mice into gland-free fat pads of
      Wnt-1 transgenic mice and found that normal MEC maintained their normal ductal
      structure in Wnt-1 fat pads without alveolar development. Further, we did not
      detect Wnt-1 mRNA expression in the gland-free fat pads of these transgenic mice.
      When Wnt-1 MEC were transplanted into the fat pads of nude mice and allowed to
      grow towards existing normal MEC, the morphology of the existing normal MEC
      remained normal. We concluded that the development of mammary hyperplasia in Wnt
      1 transgenic mice is solely dependent on Wnt-1 expression in MEC. We speculate
      that Wnt-1 may be a growth factor for mammary gland that only acts locally on the
      cells that produce it.

PMID- 1386557
TI  - Role of the alpha 5 beta 1 integrin receptor in the proliferative response of
      quiescent human melanoma cells to fibronectin.
AB  - The possible mitogenic activity of fibronectin (FN) in human primary and
      metastatic melanoma lines and clones and the involvement of integrins in
      mediating this effect were evaluated. Quescent human melanoma cells cultured in
      serum-free medium proliferated in a dose- and time-dependent fashion to
      immobilized FN as indicated by [3H]thymidine incorporation, increment of cell
      number, and cell cycle analysis. This response to FN was observed with tumor
      clones isolated from a subcutaneous metastasis and with primary or metastatic
      melanomas from different patients, but only when tumor cells expressed the alpha
      5 subunit of the FN receptor (i.e., VLA-5). Proliferation to FN by a primary
      tumor (Me4405) expressing all FN receptors and by a tumor clone (2/60) lacking
      only the alpha 4 subunit was inhibited by monoclonal antibodies to the alpha 5
      and beta 1 but not by monoclonal antibodies to other subunits of FN receptors.
      Mapping of FN regions responsible for the proliferative signal was performed by
      stimulating melanoma cells with different FN proteolytic fragments and indicated
      that a significant mitogenic signal was provided by the M(r) 120,000 alpha
      chymotrypsin fragment containing the Arg-Gly-Asp sequence. The proliferation of
      melanoma cells to FN and to FN fragments was also significantly inhibited by
      peptides containing the Arg-Gly-Asp sequence. These data indicate that FN can
      stimulate the proliferation of quiescent melanoma cells and that integrins as
      alpha 5 beta 1 are involved in the response of tumor cells to this extracellular
      matrix protein.

PMID- 1386558
TI  - Translation of the prophage lambda cl transcript.
AB  - Mutations in rpsB that reduce the levels of the ribosomal protein S2 enhance the
      translation of cl in lambda lysogens. Two features of the cl transcript are
      required for enhanced translation: the absence of a leader and the presence of a
      downstream box, a sequence within the cl coding region that is complementary to
      the 16S rRNA. 30S ribosomal subunits deficient in S2 form ternary complexes with
      the cl transcript more efficiently than wild-type subunits. The absence of S2 may
      change the structure of the 16S rRNA, improving contacts with the cl downstream
      box.

PMID- 1386559
TI  - Hepatocyte growth factor and transforming growth factor-beta stimulate both cell
      growth and migration of human gastric adenocarcinoma cells.
AB  - Hepatocyte growth factor (HGF) induced scattering and cell migration of human
      gastric adenocarcinoma MKN-74. HGF also significantly promoted the growth of MKN
      74 cells in a dose-dependent manner, although HGF is reported to be
      antiproliferative for the growth of tumor cell lines. This result indicates that
      HGF stimulates cell proliferation of not only normal epithelial cells but also
      certain carcinoma cells. Furthermore, transforming growth factor-beta (TGF-beta),
      which is recognized to inhibit the growth of most epithelial cells, additively
      enhanced both the cell proliferation and migration induced by HGF. These additive
      effects of HGF and TGF-beta may be responsible for the tumor invasiveness and
      uncontrolled growth of certain types of carcinoma.

PMID- 1386561
TI  - Fish-oil supplementation reduces Ip(a) concentrations in type III
      dysbetalipoproteinemia.

PMID- 1386560
TI  - Systemic lidocaine and human somatosensory-evoked potentials during sufentanil
      isoflurane anaesthesia.
AB  - The effect of systemically administered lidocaine on somatosensory evoked
      potentials (SSEPs) during general anaesthesia has not been widely reported.
      Knowledge of the influence of anaesthetic agents on evoked potentials assists in
      interpreting evoked potential waveforms. Accordingly, we studied the behaviour of
      cortical and subcortical (recorded at the second cervical vertebra) SSEPs after
      administration of intravenous lidocaine (3 mg.kg-1 bolus followed by infusion at
      4 mg.kg-1.hr-1) during a sufentanil-based anaesthetic regimen in 16 patients
      undergoing abdominal or orthopaedic surgery. When compared to awake baseline
      recordings, the sufentanil-nitrous oxide, low-dose isoflurane anaesthetic
      depressed N1 amplitude by approximately 40% and prolonged latency by 10%. Fifteen
      minutes after establishment of this anaesthetic, the amplitude and latency of N1
      were 1.13 +/- 0.56 microV and 19.81 +/- 1.63 msec, respectively. Within five
      minutes of adding lidocaine, amplitude decreased further to 0.84 +/- 0.39 microV
      (P = 0.001), while latency was extended to 20.44 +/- 1.48 msec (P = 0.01).
      Lidocaine did not affect cervical amplitude and prolonged latency only minimally.
      Despite the observed effects on amplitude and latency, SSEP waveforms were
      preserved and interpretable. Plasma lidocaine levels obtained at 5, 20, and 40
      minutes after lidocaine were 5.17 +/- 1.33, 3.76 +/- 1.14, and 3.66 +/- 0.9
      micrograms.dl-1, respectively. Our results indicate that systemically
      administered lidocaine at therapeutic plasma levels acts synergistically with a
      sufentanil-based anaesthetic to depress the amplitude and prolong the latency of
      SSEPs.

PMID- 1386562
TI  - Evaluating health and maturation of the unborn: the role of the clinical
      laboratory.
AB  - I review the utility of several common prenatal laboratory tests. Infant
      mortality is higher in the United States than in many other industrialized
      nations; better access to early prenatal care may help reduce this mortality
      rate. Several common laboratory tests can significantly contribute to prenatal
      care. Early measurement of maternal serum human chorionic gonadotropin can permit
      estimation of the date of conception. Use of maternal serum alpha-fetoprotein in
      the second trimester provides the clinician with risk estimates for neural tube
      defects and Down syndrome. Adding human chorionic gonadotropin and possibly
      unconjugated estriol to this screen can increase the number of Down syndrome
      cases identified without increasing the proportion of abnormal results. Amniotic
      fluid fetal lung maturity tests can assist with the management of delivery.

PMID- 1386563
TI  - On the origin of C3 nephritic factor (antibody to the alternative pathway C3
      convertase): evidence for the Adam and Eve concept of autoantibody production.
AB  - The antibody to the alternative pathway C3 convertase, designated C3 nephritic
      factor or C3NeF, is an autoantibody that is produced in everyone from the time of
      birth. The elaboration of C3NeF utilizes germline V-region genes which undergo
      antigen-driven affinity maturation, resulting in an autoantibody that is produced
      in large amounts with high affinity and narrow specificity. Our data also suggest
      that under normal conditions, the idiotypic network may play an important part in
      the control of this autoantibody. Further, a defect in the network with loss of
      control or inappropriate stimulation may be an underlying mechanism in the
      unrestricted production of C3NeF in patients with membranoproliferative
      glomerulonephritis.

PMID- 1386564
TI  - A modification of the in vivo mixed lymphocyte reaction and rapamycin's effect in
      this model.
AB  - Rapamycin, a novel macrocyclic immunosuppressive agent, suppresses murine T cell
      activation in vitro by mechanisms distinct from cyclosporin A (CsA). This study
      was designed to examine rapamycin and CsA in the host vs graft popliteal lymph
      node (PLN) model, an in vivo system of T cell-dependent lymphocyte activation.
      The PLN procedure was modified by using irradiated CTLL-2 cells of C57BL/6
      origin, instead of primary mouse splenocytes, as the allogeneic stimulus in
      C3H/HeN recipient mice. PLN cell proliferation was determined by [3H]-thymidine
      uptake. We found that the host lymphocyte proliferative response to CTLL-2 cells
      (H-2b) is greater than the response to mouse Balb/c splenocytes (H-2d). Rapamycin
      (ip or po) produced a dose-related inhibition of the in vivo mixed lymphocyte
      reaction. By contrast, the effects of CsA and FK-506 were not dose related within
      the same dose range (0.006-12 mg/kg). These data indicate that rapamycin is an
      effective immunosuppressive agent and confirm its ability to affect the
      allogeneic T cell response in vivo. Furthermore, the pharmacological data suggest
      that this PLN model utilizing irradiated CTLL-2 cells as an allogeneic stimulus
      provides a reproducible system to examine mixed lymphocyte reactions in vivo.

PMID- 1386565
TI  - Doxazosin: alternative antihypertensive treatment.

PMID- 1386566
TI  - The bactericidal activity and postantibiotic effect of trospectomycin.
AB  - Trospectomycin sulfate (trospectomycin, TRS) is a novel, broad-spectrum,
      aminocyclitol antibiotic that is being developed clinically for the treatment of
      upper respiratory tract infections, bacterial vaginosis, pelvic inflammatory
      disease, and gonorrhea. This study investigated the bactericidal activity (by
      time-kill kinetics) and the postantibiotic effect (PAE) of TRS. Species-dependent
      bacteriostatic/bactericidal activity was observed for TRS; the antibiotic was
      bacteriostatic for Staphylococcus epidermidis, Enterococcus faecalis, and
      Escherichia coli, and bactericidal for Haemophilus influenzae, Neisseria
      gonorrhoeae, Moraxella catarrhalis, and Bacteroides fragilis (one of two test
      strains). When TRS was tested at four times its minimum inhibitory concentration
      or at a maximum test concentration of 32 micrograms/ml, with a 1-hr exposure
      period, the following PAE values were recorded: S. epidermidis 30032, 1.8 hr, En.
      faecalis ATCC 29212, 1.6 hr, E. coli UC 311, 1.5 hr, E. coli UC 9451, 1.5 hr, H.
      influenzae 30063, greater than 4.0 hr, B. fragilis ATCC 25285, 5.2 hr, and B.
      fragilis UC 12199, 6.7 hr. The broad-spectrum PAE that was observed for TRS is
      somewhat unique compared with other antibiotics.

PMID- 1386567
TI  - Addition of enoximone to adrenergic agents in the management of severe heart
      failure.
AB  - OBJECTIVE: To assess the hemodynamic effects of the addition of small bolus doses
      of the phosphodiesterase inhibitor enoximone to adrenergic therapy in patients
      with severe heart failure. DESIGN: Open label, prospective study. SETTING:
      Multidisciplinary department of intensive care in a university academic hospital.
      PATIENTS: Twelve surgical patients after cardiac surgery and ten medical patients
      with ischemic or dilated cardiomyopathy who had signs of altered tissue perfusion
      associated with a low cardiac index (less than 2.25 L/min/m2), despite adrenergic
      therapy. INTERVENTIONS: Small iv bolus doses of 0.25 mg/kg of enoximone.
      MEASUREMENTS AND MAIN RESULTS: This treatment resulted in significant increases
      in cardiac index and left ventricular stroke work index without significant
      changes in heart rate or mean arterial pressure. Furthermore, the effects of half
      this dose (i.e., 0.125 mg/kg), studied in 11 patients, demonstrated a significant
      drug-induced increase in mean (+/- SD) cardiac index (from 1.58 +/- 0.29 to 1.84
      +/- 0.27 L/min/m2, p less than .01) without change in mean arterial pressure
      (from 74.5 +/- 12.1 to 76.5 +/- 12.6 mm Hg, nonsignificant). CONCLUSIONS: Direct
      iv injections of enoximone can significantly increase the cardiac index in
      critically ill patients treated by adrenergic agents for severe heart failure.
      The administration of small doses of enoximone is effective and has minimal
      effect on arterial pressure.

PMID- 1386568
TI  - Acute myopathy during treatment of status asthmaticus with corticosteroids and
      steroidal muscle relaxants.
AB  - Acute myopathy in patients being treated for severe asthma has been recognized
      with increasing frequency since first being described in 1977. We report three
      patients treated for status asthmaticus who developed severe generalized
      weakness. Electrophysiologic studies and muscle biopsy revealed evidence of
      muscle destruction. Each of these patients was treated with high-dose
      corticosteroids and underwent prolonged neuromuscular blockade with a steroidal
      muscle relaxant. A review of the literature revealed 15 similar cases. We
      postulate that the combined effects of corticosteroids and muscle relaxants on
      the muscle cell may be responsible for this myopathy. Patients treated with
      corticosteroids and NMBs should be carefully monitored for the development of
      myopathy.

PMID- 1386569
TI  - Systemic hypersensitivity vasculitis associated with bronchiectasis.
AB  - Systemic hypersensitivity vasculitis developed in a 53-year-old man during acute
      exacerbation of bronchiectasis infected with Pseudomonas aeruginosa. High grade
      fever, mononeuropathy multiplex, cutaneous vasculitis, and biopsy specimen-proved
      mesangioproliferative glomerulonephritis with crescent formation and
      leukocytoclastic vasculitis associated with circulating immune complex occurred.
      Corticosteroid and cyclophosphamide therapy was effective for vasculitis and
      bronchiectasis.

PMID- 1386570
TI  - Alterations of nucleolar ultrastructure and ribosome biogenesis by actinomycin D.
      Implications for U3 snRNP function.
AB  - We have studied, at the electron microscope level, the reorganizations of
      nucleolar ultrastructure induced by actinomycin D (AMD) in different conditions
      of drug treatment associated with an inhibition of rRNA synthesis. We have
      analyzed in parallel the localizations of ribosomal genes, of their transcripts,
      of various pre-rRNA intermediates, as well as of U3 RNA and fibrillarin by in
      situ hybridization with nucleic acid probes and immunocytological detection on
      thin sections of human and mouse cells. Consistent with previous observations,
      dense fibrillar component (DFC) and granular component (GC) appear to contain
      distinct pre-rRNA species at different stages of their processing. DFC appears as
      a major site of U3 RNA accumulation, but a very substantial fraction of nucleolar
      U3 RNA is also found in GC, colocalizing with partially processed pre-rRNAs.
      Remarkably, the major nucleolar components retain their ultrastructural
      appearance when extensively depleted of their pre-rRNA moiety, and ribosomal
      genes are always detected over fibrillar center (FC), even after extended AMD
      treatments which result in the characteristic segregation of nucleolar
      components. Moreover, while for GC the U3 RNA and pre-rRNA contents evolve in
      parallel following the cessation of rRNA synthesis, a dramatic uncoupling is
      observed for DFC. The persistent presence of U3 RNA and fibrillarin after pre
      rRNA depletion suggests that DFC could represent an anchorage site for U3 snRNPs,
      before their entering another cycle of pre-rRNA processing reactions.

PMID- 1386571
TI  - Exercise testing at 3 weeks, 6 weeks and 18 months after infarction and the
      outcome at 3 years in young patients (under 55 years).
AB  - To examine the prognostic value of routine postinfarction exercise tests in young
      patients, exercise tests were carried out at 3 and 6 weeks and 18 months after
      infarction in 149 patients aged under 55 years at the time of the index
      infarction. The patients also had coronary angiography and left ventriculography
      a mean of 3 months after infarction. Three years after infarction, only two of
      the 149 patients have died, reinfarction occurred in only seven (4.7%) patients;
      unstable angina in four (3%) patients and coronary artery surgery was needed in
      31 (20.8%) patients; 16 in the first, 10 in the second, and 5 in the third year
      of follow-up. Angina on exercise testing at 6 weeks was the only variable with
      any predictive value. Eighteen (38%) of the 47 patients with, compared to 12
      (11.8%) of the 102 patients without, angina on exercise testing at 6 weeks had
      coronary surgery (less than 0.001). None of the other exercise variables reliably
      predicted death, or other complications, including coronary surgery. Ten (13.8%)
      of the 75 patients excluded from the study died during follow-up; six of them
      within 6 weeks of infarction. Four (67%) of these patients were excluded from the
      study because of heart failure. Therefore, the 3-year outcome in young survivors
      of a myocardial infarction is good and is not reliably predicted by exercise
      testing at 3 and 6 weeks or 18 months.

PMID- 1386572
TI  - Differences in blood pressure regulation of congestive heart failure, before and
      after treatment, correlate with changes in the circulating pattern of atrial
      natriuretic peptide.
AB  - The mechanisms underlying altered BP regulation in congestive heart failure are
      unknown. This study examines the possibility that differences in circadian blood
      pressure (BP) regulation between the normal and the failing heart correlate with
      changes in the circulating pattern of atrial natriuretic peptide (ANP). Twelve
      normotensive patients with coronary artery disease were studied over two separate
      24-h periods, the first during acute exacerbation of congestive heart failure
      (radionuclide-determined ejection fraction at rest was less than 30%) and the
      second after therapy-induced functional recovery (ejection fraction was more than
      40%). BP monitoring at 10-min intervals and intra-atrial blood samples for ANP
      assays at hourly intervals were obtained. Significant correlation between
      ejection fraction and the indexes of circadian BP variability (standard deviation
      of the 24-h pressure mean and day-night pressure difference) were found both
      before and after treatment. Ejection fraction was independent of the BP means (24
      h, daytime and night-time). BP variability, 24-h mean and daytime mean were
      higher after treatment. ANP means were lower after treatment, whereas ANP
      variability was higher. The indexes of BP and ANP variability correlated both
      before and after treatment, whereas the BP and the ANP means were independent.
      These findings demonstrate that differences in BP regulation of CHF before and
      after effective treatment correlate with changes in the circulating pattern of
      ANP. We speculate that by modulating ANP release, the heart could be actively
      involved in BP regulation as part of the compensatory mechanisms aimed at
      protecting against circulatory overload.

PMID- 1386573
TI  - Amplitude analysis of stress technetium-99m methoxy isobutylisonitrile images in
      coronary artery disease.
AB  - To determine the role of rest and stress gated technetium-99m
      methoxyisobutylisonitrile (sestamibi), in the detection of coronary artery
      disease, routine Fourier analysis of these images was performed with the best
      septal left anterior oblique (LAO) position of 20 patients (17 men, 3 women; aged
      40-75 years) who also underwent rest or redistribution/stress single photon
      emission tomography (SPET) (99mTc-sestamibi and Thallium-201), gated blood pool
      imaging and coronary angiogram. There were 6 patients with single-vessel disease,
      6 with two-vessel disease, 4 with three-vessel disease, 2 with coronary spasms, 1
      with a patent graft and 1 with anginal episodes but a normal angiogram result.
      Three normal volunteers (2 women, 1 man; aged 24-26 years) also had rest and
      stress gated blood pool as well as rest and stress gated 99mTc-sestamibi imaging.
      Rest and stress 99mTc-sestamibi amplitude and phase images depicted regional
      myocardial wall shortening from the outer layer of the myocardium to the center
      of the left ventricle as follows: a high amplitude halo of maximal negative count
      rate variation; a circular thinner halo of negligible amplitude; a central region
      of maximal positive count rate variation, as the images evolved from end-diastole
      to end-systole. Similar patterns with regional differences represented abnormal
      myocardial wall shortening. 99mTc-sestamibi and 201Tl SPET images were in
      agreement in 90% of the patients and 92% of myocardial regions. 201Tl SPET
      detected 83% of angiographically proven lesions, as compared with 80% for 99mTc
      setamibi SPET and 80% for the amplitude images. The amplitude images demonstrated
      a larger number of other abnormalities not predicted on the angiogram, probably
      because they were able to detect regions with a potential for flow improvement
      and transient regional wall shortening abnormalities.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1386574
TI  - A new principle to normalize plasma concentrations allowing single-sample
      clearance determinations in both children and adults.
AB  - A sufficiently accurate quantification of renal function requiring only one
      plasma sample without an additional gamma-camera study has, until now, only been
      possible in adults. A new principle will be presented here allowing the universal
      application of known algorithms, regardless of the clearance substance used, by
      normalizing the plasma concentrations with respect to the individual body
      dimensions of the patients--for infants as well as for adults. In this respect,
      algorithms are developed for clearance determinations using technetium-99m
      mercaptoacetyltriglycine (99mTc-MAG3), which are based on steady-state studies as
      the reference. They allow the calculation of quantitative clearance values in
      infants, requiring only one blood sampling at any time between the 25th and the
      40th min postinjection. The comparison with a combined camera/two-plasma-sample
      technique performed in 46 children aged between 9 days and 14 years (mean 6.05
      years) resulted in a standard error of 8.5% from the line of identity (r = 0.94).
      Moreover, this procedure also increases the accuracy of results in adults.

PMID- 1386576
TI  - Donor alloreactivity may predict acute graft-versus-host disease in HLA-matched
      bone marrow transplantation for leukemia in early remission.
AB  - The pretransplant alloantigen-dependent responding and stimulating capacity of
      donors and of recipients was studied retrospectively, in a study of prediction of
      acute graft-versus-host disease. Donor responding capacity (DRC) and host
      stimulating capacity (HSC) were defined by mixed lymphocyte culture (MLC) and
      normalized by help of the pool response. High and low DRC and strong and weak HSC
      was defined by distribution plots. Kaplan-Meier estimates of the risk of
      developing Grade II or higher aGvHD showed that first remission patients (N =
      125) had a significantly different risk if transplanted with marrow from a donor
      with high (N = 54) or low (N = 71) DRC (chi 2 = 9.49; d.f. = 1; p less than
      0.002). This was not the case for patients transplanted in later remissions. Host
      SC status had no significant influence on the aGvHD status (chi 2 = 1.75 and
      2.40; d.f. = 1; p = 0.19 and 0.12, defined by normal controls A and B
      respectively). In conclusion, the results indicate that pretransplant donor
      alloreactivity may predict aGvHD, confirming the results from a Scandinavian
      study. The results need to be confirmed in prospective studies of alloreactivity
      as risk factor for aGvHD.

PMID- 1386577
TI  - Regulation of neuronal migration and neuritogenesis by distinct surface
      proteases. Relative contribution of plasmin and a thrombin-like protease.
AB  - The relative contribution of two neuronal surface proteases, plasmin and a
      protease with thrombin-like specificity, on NB2a/dl neuroblastoma migration and
      neuritogenesis were examined. Exogenous plasmin induced cell body rounding and
      increased cell migration, but did not prevent or reverse neurite outgrowth.
      Inhibition of endogenous plasmin by its specific inhibitor, aprotinin, suppressed
      migration but did not induce neuritogenesis. Removal or inhibition of the
      thrombin-like protease by serum deprivation or hirudin addition, respectively,
      induced neurite outgrowth, as shown in our previous studies, but did not suppress
      migration. By contrast, trypsin induced simultaneous cell rounding and neurite
      retraction. These findings indicated that plasmin may regulate cell migration,
      while the thrombin-like protease may regulate facets of neurite outgrowth.
      Although unable to induce de novo neuritogenesis, plasmin inhibition potentiated
      the otherwise transient neurites induced by simultaneous inhibition of the
      thrombin-like protease. Since cultured neuronal cells migrate primarily in the
      direction of newly elaborated neurites, this finding is interpreted to indicate
      that cessation of neuronal migration by plasmin inhibition enhances net neurite
      outgrowth by inhibition of the putative thrombin-like protease.

PMID- 1386575
TI  - The bulbar network of respiratory neurons during apneusis induced by a blockade
      of NMDA receptors.
AB  - Our aim was to study the mechanisms producing the transition from the inspiratory
      phase to the expiratory phase of the breathing cycle. For this purpose we
      observed the changes affecting the discharge patterns and excitabilities of the
      different types of respiratory neurons within the respiratory network in cat
      medulla, after inducing an apneustic respiration with the N-methyl-D-aspartate
      (NMDA) antagonist MK-801 given systemically. Respiratory neurons were recorded
      extracellularly through the central barrel of multibarrelled electrodes, in the
      ventral respiratory area of pentobarbital-anesthetized, vagotomized, paralyzed
      and ventilated cats. Inhibitions exerted on each neuron by the pre-synaptic pools
      of respiratory neurons were revealed when the neuron was depolarized by an
      iontophoretic application of the excitatory amino-acid analogue quisqualate.
      Cycle-triggered time histograms of the spontaneous and quisqualate-increased
      discharge of respiratory neurons were constructed in eupnea and in apneusis
      induced with MK-801. During apneustic breathing, the activity of the respiratory
      neuronal network changed throughout the entire respiratory cycle including the
      post-inspiratory phase, and the peak discharge rates of all types of respiratory
      neurons, except the late-expiratory type, decreased. During apneusis, the
      activity of the post-inspiratory neuronal pool, the post-inspiratory depression
      of other respiratory neurons, and the phrenic nerve after-discharge were reduced
      (but not totally suppressed), whereas the discharge of some post-inspiratory
      neurons shifted into the apneustic plateau. The shortened post-inspiration (stage
      1 of expiration) altered the organization of the expiratory phase. Late
      expiratory neurons (stage 2 of expiration) discharged earlier in expiration and
      their discharge rate increased. The inspiratory on-switching was functionally
      unaffected. Early inspiratory neurons of the decrementing type retained a
      decrementing pattern followed by a reduced discharge rate in the apneustic
      plateau, whereas early-inspiratory neurons of the constant type maintained a high
      discharge rate throughout the apneustic plateau. Inspiratory augmenting neurons,
      late-inspiratory and "off-switch" neurons also discharged throughout the
      apneustic plateau. During the apneustic plateau, the level of activity was
      constant in the phrenic nerve and in inspiratory neurons of the early-constant,
      augmenting, and late types. However, progressive changes in the activity of other
      neuronal types demonstrated the evolving state of the respiratory network in the
      plateau phase. There was a slowed but continued decrease of the activity of early
      inspiratory decrementing neurons, accompanied by an increasing activity and/or
      excitability of "off-switch", post-inspiratory and late-expiratory neurons. In
      apneusis there was a decoupling of the duration of inspiration and
      expiration.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1386578
TI  - In vitro interaction of fenretinide with plasma retinol-binding protein and its
      functional consequences.
AB  - The synthetic retinoid fenretinide (4-HPR; N-[4-hydroxyphenyl] all-trans
      retinamide) interacts with plasma apo-retinol-binding protein (RBP) to form a
      tight complex (K'd approximately 0.2 microM) which does not exhibit binding
      affinity to transthyretin (TTR). Therefore, a substantial modification of the
      retinol hydroxyl group does not appear to affect the interaction with RBP but
      does drastically interfere with the protein-protein recognition. The remarkable
      early reduction in plasma retinol level induced by fenretinide administration may
      be associated with the high binding affinity of this retinoid to RBP and to its
      interference with the RBP-TTR complex formation.

PMID- 1386579
TI  - The metastatic potential of rat prostate tumor variant R3327-MatLyLu is
      correlated with an increased activity of N-acetylglucosaminyl transferase III and
      V.
AB  - Enzyme activities of N-acetylglucosaminyltransferase (GlcNAc-Tase) I-V involved
      in N-linked complex-type carbohydrate synthesis were determined in a non
      metastatic hormone-dependent rat prostate tumor (R3327-H) and a related, hormone
      independent variant metastasizing to lymph nodes and lungs (R3327-MatLyLu). In
      the metastasizing variant a significantly increased activity of both GlcNAc-Tase
      III and GlcNAc-Tase V was observed, whereas the activities of GlcNAc-Tase I and
      II were essentially unchanged. The increase in activity of GlcNAc-Tase III is
      particularly noteworthy since it indicates that elevated expression of this
      enzyme cannot be considered as an exclusive marker of hepatic malignancy.

PMID- 1386580
TI  - Purification and characterization of phosphofructokinase in bovine parotid gland.
AB  - 1. Phosphofructokinase (PFK) was purified from bovine parotid gland to 750-fold
      with the specific activity of 67.5 units/mg protein by Cibacron Blue F3GA
      affinity chromatography, and TSK DEAE-5PW ion-exchange and TSK G4000SW size
      exclusion chromatographies on HPLC. 2. On gel-filtration, molecular weight of the
      native PFK was estimated to 400,000. 3. PFK was a heterotetramer composed of
      three kinds of subunit with molecular weights of 92,000 (C-type), 88,000 (M-type)
      and 86,000 (L-type), by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Densitometrically, relative amounts of C-, M- and L-type subunit
      were 1:1:2. 4. Under the physiological conditions of fructose 6-phosphate (Fru-6
      P) and ATP concentrations and pH, PFK activity was suppressed and hardly
      detectable. 5. Fru-6-P relieved PFK from the ATP inhibition. 6. Fructose 2,6
      bisphosphate (Fru-2,6-P2) and AMP activated PFK with a reduction of S0.5 for Fru
      6-P and subunit cooperativity. Fru-2,6-P2 was more effective than AMP.

PMID- 1386581
TI  - Timing of synthesis and cellular localization of two conidiation-specific
      proteins of Neurospora crassa.
AB  - The process of conidiation in Neurospora crassa consists of a series of distinct
      developmental stages culminating in the formation of multinucleate asexual spores
      called macroconidia. Immunoblotting techniques were used to study the timing of
      synthesis and cellular localization of CON10 and CON13, the products of two genes
      that are expressed during conidiation but not during mycelial growth. Both
      proteins first appear about 8 hr into conidiation; CON10 disappears between 2 and
      4 hr after germination. Within conidiating cultures, CON10 and CON13 proteins are
      localized in conidiophores, with little or no protein present in the underlying
      mycelium. Immunofluorescence analyses show that CON10 is evenly distributed
      throughout the cytoplasm of macroconidia. Synthesis of CON10 and CON13 occurs at
      a time when their specifying mRNAs first appear (Hager and Yanofsky, Gene 96, 153
      159, 1990; Sachs and Yanofsky, Dev. Biol 148, 117-128, 1991), suggesting that
      regulation of synthesis is predominantly transcriptional.

PMID- 1386582
TI  - Integration/mainstreaming.

PMID- 1386583
TI  - Communication aids for children: procedures and problems.
AB  - This paper describes the organisation and procedures of the Communication Aids
      Centre for children at the Wolfson Centre, London, including a model for
      assessment and recommendation of appropriate aids, such as symbol charts,
      switches and speech synthesisers. Of the children seen over an 18-month period,
      most had cerebral palsy and two-thirds were wheelchair-dependent. Almost half
      were assessed before the age of five years. A detailed follow-up of nine children
      is presented which reveals how long children may have to wait for the provision
      of an aid in the UK. Possible problems in establishing use of an aid are
      discussed; these include inadequate training of children and their communication
      partners. Suggestions for future improvements of communication-aids services are
      explored.

PMID- 1386584
TI  - The heart and control of renal excretion: neural and endocrine mechanisms.
AB  - There has been a great deal of research concerning the heart being an important
      regulator of renal fluid and electrolyte excretion. This cardiac-renal connection
      involves two different types of major mechanisms, both of which are covered in
      this review. The first of these to be discovered was neural reflex regulation.
      This type of control is due to the fact that the heart possesses nerve receptors
      whose activity is altered by changes in the degree of cardiac stretch that occur
      as a result of changes in blood volume. These receptors affect various humoral,
      neural, and perhaps hemodynamic mechanisms that modify renal excretion. A second,
      more recently discovered type of regulation is based on the concept that the
      heart is also an endocrine gland. Similar to neural receptor activity, cardiac
      hormone secretion is also linked to the degree of cardiac stretch or filling.
      These cardiac peptides have been shown to have a variety of physiologic effects,
      most of which directly or indirectly affect renal excretion. Both of the above
      cardiorenal control mechanisms, one neural and one humoral, may be important not
      only in maintaining normal fluid-electrolyte balance but may also have
      pathophysiologic relevance.

PMID- 1386585
TI  - Therapeutic potential of modulating potassium currents in the diseased
      myocardium.
AB  - Myocardial disease states are characterized by multiple electrophysiologic
      abnormalities, including alterations in potassium channel activities. During
      acute myocardial ischemia, activation of ATP-regulated K+ current (IK(ATP))
      results in shortening of action potential duration and elevation of extracellular
      K+ concentration. In hypertrophied myocardium, increases in inward rectifier K+
      current (IK1) and decreases in delayed rectifier K+ current (IK) are observed.
      Alterations in K+ channel activity in myocardial disease states suggest the
      potential to therapeutically modify cardiac rhythm and function with K+ channel
      modulators. Class III anti-arrhythmic agents, which prolong myocardial
      refractoriness predominantly via a blockade of IK, have demonstrated efficacy in
      suppressing reentrant atrial and ventricular arrhythmias in animal models as well
      as promising efficacy in initial clinical studies. Potassium channel openers
      (PCOs), which activate cardiac IK(ATP), have demonstrated both antiarrhythmic and
      proarrhythmic activities in various experimental settings, and also are being
      investigated as potential cardioprotective agents. Sulfonylureas, which block
      cardiac IK(ATP), also have been investigated as potential antiarrhythmic agents
      with equivocal results, and have displayed a propensity to exacerbate ischemic
      myocardial dysfunction in experimental studies. A more comprehensive
      understanding of K+ channel activity in various myocardial disease states,
      including concomitant disorders such as myocardial ischemia and hypertrophy, will
      facilitate the development of more useful potassium channel modulators, as well
      as a clearer recognition of the undesirable effects of such agents.

PMID- 1386587
TI  - Subchronic toxicity study of Caramel Colour II in F344 rats.
AB  - Caramel Colour II is a distinct type of colourant with a pronounced reddish hue.
      It is made with sulphite reactants but without ammonia. The red colour and a high
      alcohol solubility provide functional characteristics that are important in foods
      or beverages containing natural flavour extractives. Caramel Colour II is widely
      used in ice creams and liqueurs; however, it represents less than 1% of total
      caramel colour manufacture. The toxicity of Caramel Colour II was evaluated in a
      13-wk study in Fischer-344 (F344) rats. The test material was mixed with
      demineralized water and the solutions were given to the animals ad lib. in the
      drinking fluid. The concentrations of caramel colour in the drinking fluid were
      adjusted periodically to achieve the desired caramel colour intake/kg body
      weight/day. Groups of 20 rats/sex were given Caramel Colour II at levels of 0, 4,
      8, 12 or 16 g/kg for at least 13 wk. There were no deaths in any of the groups
      fed Caramel Colour II. All rats fed caramel colour had soft faeces. All treated
      groups also had lower fluid consumption that was attributed to poor palatability
      of the high concentrations of caramel colour that were fed. A number of changes
      observed (reduced food consumption in all treatment groups except males given 4
      g/kg; significantly lower body weights for males given 12 g/kg or more and for
      females given 8 g/kg or more; lower urine volume and higher specific gravity)
      were attributed to the reduced water intake and not considered to be
      toxicologically significant. There were no consistent treatment-related
      alterations in haematology or blood chemistry variables, and random changes noted
      were not associated with macroscopic or microscopic pathological alterations.
      There were no toxicologically important pathological findings. Based on this
      study, Caramel Colour II was not toxic in F344 rats treated for 13 wk. The
      highest dose level tested in this study (16 g/kg) was considered to be the no
      observed-adverse-effect level.

PMID- 1386588
TI  - [Eligibility for intensive nursing care. Part 1: Guidelines and current
      experience].
AB  - Against the background of the planned statutory Pflegeversicherung (insurance for
      nursing care) in Germany, a report is presented on experience gained to date with
      the new Leistungsbestand "Schwerpflegebedurftigkeit" (situation requiring social
      benefit "urgent need of nursing care") (Para. 53 ff. SGB V). The experience
      gained so far is of particular interest since, for the first time on a large
      scale, monetare Erstattungsleistung (the provision of a monetary entitlement)
      replaces the Sachleistungsprinzip (benefit in the form of services) that is
      otherwise applied in the area of health insurance. It is intended that this form
      of entitlement will form the core of the planned nursing care insurance scheme.

PMID- 1386586
TI  - A novel mitochondrial genome organization for the blue mussel, Mytilus edulis.
AB  - The sequence of 13.9 kilobases (kb) of the 17.1-kb mitochondrial genome of
      Mytilus edulis has been determined, and the arrangement of all genes has been
      deduced. Mytilus mitochondrial DNA (mtDNA) contains 37 genes, all of which are
      transcribed from the same DNA strand. The gene content of Mytilus is typically
      metazoan in that it includes genes for large and small ribosomal RNAs, for a
      complete set of transfer RNAs and for 12 proteins. The protein genes encode the
      cytochrome b apoenzyme, cytochrome c oxidase (CO) subunits I-III, NADH
      dehydrogenase (ND) subunits 1-6 and 4L, and ATP synthetase (ATPase) subunit 6. No
      gene for ATPase subunit 8 could be found. The reading frames for the ND1, COI,
      and COIII genes contain long extensions relative to those genes in other metazoan
      mtDNAs. There are 23 tRNA genes, one more than previously found in any metazoan
      mtDNA. The additional tRNA appears to specify methionine, making Mytilus mtDNA
      unique in having two tRNA(Met) genes. Five lengthy unassigned intergenic
      sequences are present, four of which vary in length from 79 to 119 nucleotides
      and the largest of which is 1.2 kb. The base compositions of these are
      unremarkable and do not differ significantly from that of the remainder of the
      mtDNA. The arrangement of genes in Mytilus mtDNA is remarkably unlike that found
      in any other known metazoan mtDNA.

PMID- 1386589
TI  - [Ondansetron--the first highly selective 5-HT3 antagonist in therapy of
      psychiatric diseases].
AB  - Ondansetron is a highly selective 5-HT3 antagonist, which has recently become
      available for the control of chemotherapy-induced emesis. Since 5-HT3 receptors
      not only have a high density in the area postrema but also in the hippocampal and
      amygdala region of the limbic system, it has been suspected that 5-HT3 selective
      agents have psychotropic effects. In animal models of anxiety ondansetron showed
      a benzodiazepine-like anxiolytic effect without any sedation or withdrawal
      effects. Other states of withdrawal have been prevented with ondansetron. This
      agent might also exert neuroleptic effects since dopaminergic hyperactivity in
      the mesolimbic system was antagonised by ondansetron. In different models of
      memory and learning a positive effect on basal learning behaviour and on
      scopolamine-induced memory impairment was noted. This manuscript reviews
      essential pharmacological and behavioural effects of ondansetron as well as
      preliminary data from clinical studies. The role of highly-selective ligands for
      a more differentiated view of serotonergic subsystems are discussed.

PMID- 1386591
TI  - Risk factors in wound infection following urologic operations: a prospective
      study.
AB  - A total of 134 urologic operations were studied prospectively for postoperative
      wound infection, the methodology involving direct intraoperative swab taking.
      Patients' variables were (mean +/- SD): age 32.4 +/- 20.7 years, Quetelet index
      27.4 +/- 8, duration of operation 98 +/- 34 minutes, and male:female ratio 9.3:1.
      Of the 131 intraoperative swabs 28 (21%) were positive, 97% of the organisms
      being aerobic; 16% of the patients were nasal carriers of S. aureus. The overall
      wound infection rate was 9%, and it prolonged hospital stay by six days average.
      Significant risk factors (and their magnitude) were: age over 60 years (x 2.2),
      prolonged preoperative hospital stay (x 15), and wound contamination (x 4.3 and x
      14.3 for classes 3 and 4 wounds respectively). Neither diabetes mellitus,
      obesity, nor surgeon's rank was contributory. We conclude that, although the 9%
      rate of postoperative wound infection was acceptable, appropriate prophylactic
      antibiotics may reduce it further, and, from our data, we would recommend an
      aminoglycoside (e.g. Amikacin) and Ampicillin combined.

PMID- 1386590
TI  - In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203
      strains of Haemophilus influenzae.
AB  - The in vitro activity of clarithromycin alone and in combination with its primary
      human metabolite, 14-hydroxy-clarithromycin, was determined against 203 strains
      of Haemophilus influenzae. Microdilution broth MICs and MBCs of both
      clarithromycin and 14-hydroxy-clarithromycin were determined. The clarithromycin
      MIC50 was 4 mg/l and the MIC90 was 8 mg/l. The hydroxy metabolite was 2-4-fold
      more active with an MIC50 and MIC90 of 2 mg/l. The MBCs were equal to the MICs.
      The microbicidal effect of combinations of clarithromycin and 14-hydroxy
      clarithromycin was tested using a microdilution checkerboard technique and the
      fractional inhibitory index was calculated. The combination was additive in 92%
      and synergistic in 8% of all strains of H. influenzae tested; no antagonism was
      found. The results were independent of the site of isolation of the strain or
      presence of beta-lactamase. These findings suggest the potential clinical utility
      of clarithromycin for the treatment of H. influenzae infections.

PMID- 1386592
TI  - The epidemiology of environmental tobacco smoke (ETS) and the weight of evidence
      argument.
AB  - This paper demonstrates that Wald's meta-analysis is an unadjusted combination of
      unadjusted estimates. There are many differences among the design and
      implementation of the original studies combined here. One consequence of these
      differences is that studies of spousal smoking and lung cancer mortality
      conducted in the United States have a lower combined RR than those done
      elsewhere. Here it is shown that adjustment for this stratification results is a
      non significant finding as to the association of ETS with lung cancer. Likewise,
      the addition, for illustration, of Varela's Ph.D. thesis that is the largest case
      control study to date, changes the overall results from a significant to a non
      significant result. This paper does not attempt to update Wald's meta-analysis
      with more recent studies. This is being done, I believe by the Environmental
      Protection Agency. I have given here my reasons for suspecting the conclusions of
      meta-analysis of non-randomized studies and the illustrations provided here of
      the effect of publication bias and covariate adjustment support this view.

PMID- 1386594
TI  - Able, willing, and available.

PMID- 1386593
TI  - Abdominal colpopexy for complete prolapse of the vagina.
AB  - A comparative study of abdominal colpopexy using rectus fascia and sacral
      fixation for the treatment of prolapsed vagina following hysterectomy was
      performed. The abdominal approach yields better results than the vaginal route.
      Fixation of the vaginal vault using a Dacron prosthesis is more rational and was
      the method of choice, resulting in a complete cure in 10 of 11 patients. The
      Brady technique failed in 25% of cases.

PMID- 1386595
TI  - [Negative appendectomies can be decreased by improved clinical assessment alone].
AB  - We had a 20% rate of negative appendectomies in our patients presenting with
      suspected appendicitis. We suggested that an improved clinical examination would
      reduce this rate. 84 consecutive patients presenting with suspected acute
      appendicitis were prospectively studied. 10 clinical features were used to
      calculate a score which should distinguish appendicitis and non-specific
      abdominal pain. 53 appendectomies with 6 (11.3%) perforations, 41 (77.4%) acute
      inflammations and 6 (11.3%) normal appendixes have been performed. 26 patients
      suffered from non-specific abdominal pain, 5 had an other surgical disease. In
      the appendectomized patients the score was 4.2 +/- 1.2 with perforation, 4.4 +/-
      1.1 with acute inflammation and 3.8 +/- 1.3 with a normal appendix (p = ns). The
      score for non-specific abdominal pain in patients without operation was
      significantly lower (2.0 +/- 1.1; p less than 0.01). Patients with other surgical
      disease had a score of 2.8 +/- 1.5 with no significant difference to patients
      which had undergone appendectomy. Negative appendectomies were reduced by
      improved clinical examination from 20.3% to 11.3% without change in the rate of
      perforation. The remaining patients with negative appendectomies could not be
      identified by improved clinical examination even by means of the score. But the
      use of the score improved the performance of the clinicians.

PMID- 1386596
TI  - [Appendectomy: open or laparoscopic?].
AB  - Surgeons interest in laparoscopic surgery has grown considerably in the last
      years, mostly due to the explosive spread of laparoscopic cholecystectomy.
      Laparoscopic appendectomy is from a historical point of view the older procedure,
      since it was already performed 1982 by Semm. His technique was modified 1987 by
      Gotz, who is also responsible for popularizing it in general surgery. Between
      April 1989 and April 1991 we have performed 107 laparoscopic appendectomies. 82
      were completed successfully by laparoscopy, in 25 instances we had to convert to
      an open procedure, mostly as a result of the lack of proficiency in the learning
      period. There were 8 septic complication (9.7%), a rather high rate, which
      probably will be reduced with the increasing operative expertise. There were no
      deaths in this series. Further experience is demanded in order to establish
      laparoscopic appendectomy as the alternative to the conventional procedure.

PMID- 1386597
TI  - [Is routine intra-operative cholangiography in laparoscopic cholecystectomy truly
      unnecessary?].
AB  - The introduction of laparoscopic cholecystectomy as method of choice for gall
      stone treatment reopened the question whether to continue with routine
      intraoperative cholangiography or to switch over to a selective indication. In
      order to set an accurate indication for selective intraoperative cholangiography
      it was our goal to develop a tool for preoperative identification of patients
      with a high risk of common bile duct stones. A preoperative score, indicating the
      risk of common bile duct stones, was designed. A history of jaundice, elevated
      levels of bilirubin, alkaline phosphatase, amylase (serum), ALAT (GPT) or ASAT
      (GOT), a common bile duct wider than 10 mm or containing concrements and multiple
      gallstones smaller than 10 mm were valued as risk indicators, whereas normal wide
      bile duct, large or solitary gallstones were valued as decreasing the risk of
      common bile duct stones. The retrospective screening of 289 consecutive
      conventional cholecystectomies (1986-1990) for these risk indicators demonstrated
      a good correlation of the risk score with the occurrence of common bile duct
      stones. A prospective application of the score, with improved ultrasound
      examination and routine preoperative intravenous cholangiography, mandatory for
      laparoscopic cholecystectomy at our institution, will define the high risk group
      definitely and allow an accurate selective use of intraoperative cholangiography.

PMID- 1386598
TI  - [The gallbladder with severe pathologic changes: a contraindication for
      laparoscopic cholecystectomy?].
AB  - In the beginnings of laparoscopic cholecystectomy a severe pathological
      alteration of the gallbladder or stones of the common bile duct were regarded as
      relative contraindications to the method. However increasing experience and
      improve technic have shown, that even a severe pathology of the gallbladder such
      as chronic cholecystitis with wall thickening, acute or subacute inflammation or
      a porcelaine gallbladder can be laparoscopically managed. Operation time in such
      cases is longer, but median hospital stay is the same as in uncomplicated cases.
      However postoperative morbidity may be increased. For patients with CBD stones
      preoperative ERCP with papillotomy followed by laparoscopic cholecystectomy some
      days later offers a treatment with low morbidity and optimal comfort for the
      patient.

PMID- 1386599
TI  - Trust informs members on disability benefits.

PMID- 1386600
TI  - A reevaluation of estimates of child therapy effectiveness.
AB  - In a recent review of nonbehavioral child and adolescent psychotherapy, it was
      concluded that the magnitude of methodological flaws in this body of research
      precluded an evaluation of effectiveness. However, recent quantitative reviews of
      child and adolescent therapy have concluded that nonbehavioral therapy is
      relatively ineffective compared with behavioral therapy. A sample of
      nonbehavioral studies was reviewed to evaluate the adequacy of estimates of
      effectiveness. Three contributions to inaccurate effect estimation were
      considered: methodological quality, investigator allegiance effects, and
      treatment representativeness. It was concluded that all three factors contribute
      to inaccurate estimates of the effectiveness of child and adolescent
      psychotherapy. Recommendations for improving child therapy research are
      considered in light of these revealed problems.

PMID- 1386602
TI  - Characterization of autoantibodies that recognize U4/U6 small ribonucleoprotein
      particles in serum from a patient with primary Sjogren's syndrome.
AB  - We identified autoantibodies that recognize the U4/U6 snRNPs in a serum from a 63
      year-old Japanese patient (TT) with primary Sjogren's syndrome. This patient's
      serum immunoprecipitated U4 and U6 sn-RNAs exclusively from 32P-labeled HeLa cell
      extracts and a newly identified 120-kDa protein along with the Sm core proteins
      (B'/B, D, E, F, and G) from [35S] methionine-labeled HeLa cell extracts.
      Immunoblotting demonstrated that only the 120-kDa protein was recognized by this
      unique serum. In glycerol density gradient centrifugation, the 120-kDa protein
      reactive with TT serum cosedimented with U4 and U6 snRNAs, suggesting that the
      120-kDa protein is a unique component of the U4/U6 snRNP particle. In the same
      study, the U4/U6 snRNP precipitated by TT serum sedimented only in the lower
      density, whereas anti-Sm antibodies precipitated U4/U6 snRNAs in a broad range of
      the gradient. This result suggests the presence of at least two molecular forms
      of the U4/U6 snRNP particles; larger particles, probably the U4/U5/U6 snRNP
      complex, and free particles. Thus, the U4/U6 snRNP recognized by TT serum
      includes the U4 and U6 snRNAs, with Sm core proteins, and the novel 120-kDa
      protein, and appears to be a free particle not associated with larger complexes.

PMID- 1386601
TI  - The NH2 terminus of retinal recoverin is acylated by a small family of fatty
      acids.
AB  - Recoverin is a recently identified Ca(2+)-binding protein that imparts Ca2+
      sensitivity to vertebrate photoreceptor guanylate cyclase. In response to photo
      induced depletion of intracellular cGMP and Ca2+, recoverin stimulates
      resynthesis of cGMP. Bovine retinal recoverin has now been analyzed by
      electrospray mass spectrometry (ESI-MS) for post-translational modifications that
      might influence its activity. Heterogeneous acylation was detected at the NH2
      terminus of bovine retinal recoverin. The NH2-terminal glycine of each retinal
      recoverin molecule is linked to one of four different types of acyl groups. The
      most abundant is myristoleate (14:1), but 14:0, 14:2, and 12:0 acyl residues are
      also present.

PMID- 1386603
TI  - Molecular dissection of the beta subunit of F1-ATPase into peptide fragments.
AB  - Partial digestion of the native beta subunit of F1-ATPase from the thermophilic
      Bacillus strain PS3 by three different proteases produced a limited number of
      peptide fragments. In most cases, the peptides remained associated, and the gross
      structure of the beta subunit was not destroyed. Furthermore, most peptides were
      able to reassociate into the form of the beta subunit after denaturating urea
      treatment. Therefore, the cleaved sites are most likely located in water-exposed
      loop regions in the tertiary structure of the protein. Almost all peptides were
      analyzed, and 17 cleaved sites were determined. From the analysis of the
      distribution of cleaved sites and deletions or insertions in the multiple amino
      acid sequence alignment of proteins homologous to the beta subunit, locations of
      five loops and four candidate loops in the beta subunit are suggested. There are
      two large loops in the central region of the beta subunit sequence, and
      dicyclohexylcarbodiimide-reactive Glu190 is located in one of them. Tyr341,
      involved in putative catalytic ATP binding, is also found in one of the loops.
      Then, taking cleaved sites as a reference, two kinds of expression plasmids, each
      of which carried genes of two complementary peptide fragments, 1-193 and 198-473
      or 1-284 and 285-473, were constructed and expressed in Escherichia coli. For
      each plasmid, two peptides were coexpressed, associated into a stable beta
      subunit form in E. coli cells, and purified without dissociation. When these beta
      subunits were denatured by urea and applied to polyacrylamide gel without
      denaturant, a protein band with the same mobility as that of the beta subunit
      appeared, indicating that reassociation of peptide fragments into the form of the
      beta subunit occurred upon removal of urea. These beta subunits retained the
      ability to reconstitute the alpha 3 beta 3 gamma complexes even though the
      efficiency of reconstitution and the recovered ATPase activities were decreased.
      These complexes were stable at high or low temperature, and ATPase activities
      were sensitive to inhibition by N3-.

PMID- 1386605
TI  - Evidence for monomeric and dimeric forms of CD45 associated with a 30-kDa
      phosphorylated protein.
AB  - Glycoprotein CD45, a transmembrane protein tyrosine phosphatase of leukocytes, is
      topographically similar to the epidermal growth factor receptor, a transmembrane
      tyrosine kinase. Since the latter is thought to be allosterically regulated
      through conversion between monomeric and dimeric forms, we sought to determine
      whether CD45 undergoes similar oligomerization. Our analysis, employing a thiol
      cleavable and homobifunctional chemical cross-linker, dithiobis succinimidyl
      propionate, revealed that CD45 indeed formed homodimers. In addition, a protein
      of molecular mass 30,000 daltons (30 kDa) was found to be associated with both
      the CD45 monomer and dimer. The 30-kDa protein was phosphorylated and was not
      labeled by cell surface radioiodination. Distinct differences in protein tyrosine
      phosphatase activity were detected among the various populations of CD45
      separated by sucrose gradient ultracentrifugation. However, the differences
      observed could not be explained simply by dimerization and instead suggest the
      presence of other factor(s) involved in the regulation of CD45 enzyme activity.

PMID- 1386606
TI  - Tremor, confusion, and autonomic dysfunction in Down syndrome.

PMID- 1386604
TI  - Localization and characterization of a 7.3-kDa region of caldesmon which
      reversibly inhibits actomyosin ATPase activity.
AB  - Cleavage of caldesmon with chymotrypsin yields a series of fragments which bind
      both calmodulin and actin and inhibit the binding of myosin subfragments to actin
      and the subsequent stimulation of ATPase activity. Several of these fragments
      have been purified by cation exchange chromatography and their amino-terminal
      sequences determined. The smallest fragment has a molecular mass of about 7.3 kDa
      and extends from Leu597 to Phe665. This polypeptide inhibits the actin-activated
      ATPase of myosin S-1; this inhibition is augmented by smooth muscle tropomyosin
      and relieved by Ca(2+)-calmodulin. The binding of the 7.3-kDa fragment to actin
      is competitive with the binding of S-1 to actin. Thus, this polypeptide has
      several of the important features characteristic of intact caldesmon. However,
      although an intact caldesmon molecule covers between six and nine actin monomers,
      the 7.3-kDa fragment binds to actin in a 1:1 complex. Comparison of this fragment
      with others suggests that a small region of caldesmon is responsible for at least
      part of the interaction with both calmodulin and actin.

PMID- 1386607
TI  - An unusual splicing mutation in the HEXB gene is associated with dramatically
      different phenotypes in patients from different racial backgrounds.
AB  - Sandhoff disease is caused by mutations affecting the beta subunit of lysosomal
      beta-hexosaminidase (EC 3.2.1.52) and displays a wide spectrum of clinical
      phenotypes. We report a 57-year-old patient with a very mild phenotype, although
      residual hexosaminidase A activity in his cultured fibroblasts was less than 3%
      of normal activity, a level observed in juvenile onset patients. Northern and
      Western blot analyses confirmed a similar low level of beta subunit-mRNA and
      mature beta-protein, respectively. Two mutations of the HEXB gene were identified
      in this patient, a partial 5' gene deletion (a null allele), and a C----T
      transition 8 nucleotides downstream from the intron 10/exon 11 junction affecting
      the splicing of the beta subunit-mRNA. In their homozygous forms, the 5' deletion
      has been previously shown to result in a severe infantile phenotype, and the C---
      T transition in a juvenile phenotype. The genotype and the low level of residual
      hexosaminidase A activity would be expected to produce a juvenile Sandhoff
      phenotype in this patient, as well as in four of his six clinically normal
      siblings. The biochemical basis of his mild phenotype is uncertain, but may
      result from genetic variations in the RNA splicing machinery.

PMID- 1386608
TI  - Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium.
AB  - RA is characterized by massive proliferation of synovial tissue, accompanying
      infiltration of the tissue with CD4+ T lymphocytes, and a genetic linkage to the
      MHC antigen HLA-DR4. Since T cells are restricted by class II MHC molecules such
      as DR4, this suggests a direct role for these CD4+ cells in pathogenesis. To
      investigate T cell receptor (TCR) usage in RA, we used oligonucleotide primers
      specific for each of the major alpha and beta TCR subfamilies to amplify cDNA
      derived from whole synovium or synovial tissue T cell lines in a family-specific
      manner. Detection of amplified DNA was facilitated by utilizing oligonucleotide
      probes derived from the constant regions of the TCRs. The TCR repertoire present
      in the synovial T cell lines was quite heterogeneous, with an average of 15 alpha
      chains and 15.8 beta chains detected. When synovial tissue was analyzed, the
      predominant TCR subfamilies detected tended to be more restricted, with an
      average of 4.6 alpha chains and 8.6 beta chains detected. This compared with an
      average of six alpha chains and 12 beta chains in nonrheumatoid synovial samples.
      The average percentage of synovia positive per TCR beta family was significantly
      lower for RA versus non-RA specimens (46.1 vs 65.6%, P = 0.034). These findings
      indicate that while a polyclonal population of T cells is present in RA synovium,
      the predominant patterns of TCR transcript expression may be somewhat more
      restricted, suggesting that TCR-based therapy of RA is possible.

PMID- 1386610
TI  - Surface expression of Fc gamma receptor III (CD16) on chemoattractant-stimulated
      neutrophils is determined by both surface shedding and translocation from
      intracellular storage compartments.
AB  - Stimulation of neutrophils (PMN) with chemoattractants markedly increases surface
      expression of several membrane proteins, including the complement receptors, CR1
      and CR3, by translocation from intracellular storage compartments to the cell
      surface. When we stimulated freshly-isolated PMN with FMLP, we observed little
      net change in surface Fc gamma receptor (R) III expression. However, if elastase
      was first used to cleave most (85-90%) of the Fc gamma R III from the PMN
      surface, subsequent treatment with FMLP induced a rapid renewal of surface Fc
      gamma R III, achieving levels of approximately 70% of that originally present on
      the cell surface after 15 min, suggesting translocation of intracellular
      receptors. This was confirmed by demonstrating concomitant depletion of greater
      than 80% of the intracellular Fc gamma R III. Studies of density gradient
      fractions of N2-cavitated PMN indicated at least two distinct intracellular
      membrane fractions that contain Fc gamma R III. Shedding of Fc gamma R III
      induced by FMLP was about half-maximal by 15 min and nearly complete by 60 min.
      Stoichiometric assessment of FMLP-induced changes in PMN surface and
      intracellular Fc gamma R III showed a marked depletion in intracellular Fc gamma
      R III, little net change in surface Fc gamma R III, and a large overall loss of
      total cell Fc gamma R III that could be attributed to shedding. We conclude that
      stimulation by chemoattractants causes a rapid translocation of intracellular Fc
      gamma R III to the PMN surface that is roughly balanced by the concomitant FMLP
      induced shedding of this receptor.

PMID- 1386609
TI  - A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld
      disease.
AB  - In mice, the two distinct autosomal recessive genes lpr and gld can induce a
      syndrome characterized by autoantibody formation and the progressive accumulation
      of an unusual CD4-CD8- T cell population in peripheral lymphoid tissue. This
      phenotype does not precisely mirror any human disease. In this report we describe
      two patients with a progressive lymphoproliferative disorder associated with
      autoimmunity. The peripheral blood and lymph nodes of these patients contained
      large numbers of an unusual CD4-CD8- T cell population. These CD4-CD8- T cells
      express surface markers characteristic of mature peripheral blood T cells (CD3,
      CD2, CD5), express the alpha/beta form of the T cell receptor, and do not express
      surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16,
      CD56). Functionally, these cells exhibited deficient proliferation and lymphokine
      production upon stimulation with mitogenic antibodies to CD3 or CD2. Both
      proliferation and lymphokine production could be augmented by co-stimulation with
      an antibody directed at the CD28 determinant. The clinical and immunological
      features of this syndrome resemble the lymphoproliferative/autoimmune disease
      seen in lpr and gld mice.

PMID- 1386611
TI  - Human neutrophil annexin I promotes granule aggregation and modulates Ca(2+)
      dependent membrane fusion.
AB  - The mechanism and cofactor requirements of exocytotic membrane fusion in
      neutrophils are unknown. Cytosolic proteins have been implicated in membrane
      fusion events. We assessed neutrophil cytosol for the presence of fusogenic
      proteins using a liposome fusion assay (lipid mixing). A fusogenic 36-kD protein
      containing amino acid sequence homology with human annexin I was purified from
      the cytosol of human neutrophils. This protein also shared functional
      characteristics with annexin I: it associated with and promoted lipid mixing of
      liposomes in a Ca(2+)-dependent manner at micromolar Ca2+ concentrations. The 36
      kD protein required diacylglycerol to promote true fusion (contents mixing) at
      the same Ca2+ concentrations used for lipid mixing. The 36-kD protein exhibited a
      biphasic dose-response curve, by both promoting and inhibiting Ca(2+)-dependent
      lipid-mixing between liposomes and a plasma membrane fraction. The 36-kD protein
      also promoted Ca(2+)-dependent increases in aggregation of a specific granule
      fraction, as measured by a turbidity increase. Antiannexin I antibodies depleted
      the 36-kD protein from the cytosol by greater than 70% and diminished its ability
      to promote lipid mixing. Antiannexin I antibodies also decreased by greater than
      75% the ability of neutrophil cytosol to promote Ca(2+)-dependent aggregation of
      the specific granules. These data suggest that annexin I may be involved in
      aggregation and fusion events in neutrophils.

PMID- 1386613
TI  - Osteogenesis and growth of the nasal ventral conchae of the piglet.
AB  - The present study investigated the osteogenesis and growth of the nasal ventral
      conchae of piglets aged from 1 to 28 days. Serial transverse sections of paraffin
      wax-embedded noses were stained and examined by light microscopy. Bone formation
      occurred in a rostrocaudal direction in the ventral scroll, dorsal scroll,
      connecting zone, transverse lamina and articular lamina, successively, and
      occurred by two ossification processes: endochondral ossification and
      intramembranous bone apposition. Endochondral ossification was responsible for
      the longitudinally, rostrally directed growth. Rapid transverse bone growth and
      modelling were centrifugally directed and occurred by intramembranous bone
      apposition at the eccentric side of the scrolls and resorption at the concentric
      scroll side. Elongation of the distal scroll extremities took place by
      intramembranous bone apposition.

PMID- 1386614
TI  - Oral spironolactone therapy in male patients with rosacea.
AB  - Spironolactone at 50 mg/day was orally administered for four weeks to 13 male
      patients with rosacea in order to observe its clinical effectiveness. Serum
      estradiol (E2), 17OH-progesterone (17OH-P4), testosterone (T), androstenedione
      (delta 4 A), dihydrotestosterone (DHT), dehydro-epiandrosterone sulfate (DHEA-S)
      were measured prior to and after treatment. Although there were no significant
      changes in T, delta 4A, DHT, or DHEA-S, the serum levels of 17OH-P4 increased
      significantly. E2 tended to increase, although the change was not significant.
      Two of the 13 patients discontinued spironolactone treatment because of general
      malaise, but seven of the remaining eleven patients exhibited an improvement in
      their rosacea. These findings demonstrate that a low dose of spironolactone is
      effective in the treatment of rosacea in some male patients and suggest that it
      is possible that changes in the metabolism of sex steroid hormones such as
      cytochrome p-450 isozymes have some bearing on the etiology of rosacea.

PMID- 1386615
TI  - Exfoliative dermatitis as a risk factor for epidemic spread of methicillin
      resistant Staphylococcus aureus.

PMID- 1386612
TI  - Interleukin-1 receptor antagonist in normal and psoriatic epidermis.
AB  - The objective of these studies was to characterize the IL-1 inhibitory activity
      present in normal and psoriatic epidermis from clinically stable lesions.
      Fractionation of normal epidermal cytosol on a molecular sizing column failed to
      reveal the presence of IL-1 inhibitory bioactivity. However, specific ELISAs
      indicated that both the IL-1 receptor antagonist (IL-1ra) and IL-1 alpha were
      present in overlapping peaks. Further fractionation of the normal epidermal
      cytosol by anion exchange chromatography separated these two molecules, revealing
      the IL-1 inhibitory bioactivity of the IL-1ra molecule. Similar studies on
      psoriatic epidermal cytosol indicated the presence of IL-1 inhibitory bioactivity
      and IL-1ra protein. The IL-1 inhibitory bioactivity of both normal and psoriatic
      cytosol was neutralized by a mAb specific for IL-1ra. The ratio of IL-1ra to IL-1
      alpha proteins was significantly increased in involved psoriatic skin compared
      with normal skin. By Western blot analysis this IL-1ra was approximately 20 kD,
      slightly larger than monocyte-derived IL-1ra and equivalent to an intracellular
      variant of IL-1ra expressed by keratinocytes. Polymerase chain reaction indicated
      the presence of mRNA for both forms of IL-1ra in normal epidermis, with both
      forms increased in psoriatic-involved skin. Immunofluorescence studies revealed
      the IL-1ra protein to be concentrated in the stratum granulosum of normal skin
      and in the basal-midbasal layers of psoriatic epidermis. These results suggest
      that the balance between intracellular IL-1ra and IL-1 alpha may be an important
      influence on keratinocyte growth and/or differentiation, as well as on the
      inflammatory potential of IL-1 in injured skin.

PMID- 1386616
TI  - Experiences of informal carers providing nursing support for disabled dependants.
AB  - This paper provides an account of the experience of a group of informal carers
      who provided nursing support for their physically disabled dependants. The
      project was designed to establish the extent to which carers are equipped to
      fulfil their role in terms of equipment, facilities, skills, levels of personal
      health and the extent of support available to them from agencies outside the
      home. The carers were found to be providing the majority of nursing support
      required by their dependants. This mainly involved carrying out tasks of personal
      care although, for some, more technical procedures were involved. The findings
      indicate there is scope for professional nurses to make a greater contribution to
      the support of informal carers, particularly by regular review of the nature and
      level of assistance which carers provide and by giving training in the skills
      which carers require.

PMID- 1386617
TI  - Field-testing the new DECtalk PC system for medical applications.
AB  - Synthesized human speech has now reached a new level of performance. With the
      introduction of DEC's new DECtalk PC, the small system developer will have a very
      powerful tool for creative design. It has been our privilege to be involved in
      the beta-testing of this new device and to add a medical dictionary which covers
      a wide range of medical terminology. With the inherent board level understanding
      of speech synthesis and the medical dictionary, it is now possible to provide
      full digital speech output for all medical files and terms. The application of
      these tools will cover a wide range of options for the future and allow a new
      dimension in dealing with the complex user interface experienced in medical
      practice.

PMID- 1386618
TI  - Huntington's disease in Thailand: a case report.
AB  - The first documented case of Huntington's Disease (HD) in Thailand is reported.
      The patient presented with classical clinical picture, clinical course and family
      history. Although hereditary chorea is most frequently associated with HD, other
      hereditary basal ganglion diseases, Syndenham's chorea, and other causes of
      abnormal movements were considered and excluded by clinical profiles and
      investigations. Various recent aspects of HD are briefly mentioned.

PMID- 1386619
TI  - Low back pain in eight areas of Britain.
AB  - STUDY OBJECTIVE: The aim was to assess the geographical variation in low back
      pain and associated disability in Britain. DESIGN: This was a cross sectional
      survey with information collected by postal questionnaire. SETTING: General
      practices in seven British towns and one rural district. SUBJECTS: 1172 men and
      1495 women aged 20-59 years were selected from the age-sex registers of 136
      general practitioners in the study areas. MAIN RESULTS: The overall lifetime and
      one year period prevalences of low back pain were 58.3% and 36.1%. Rates in men
      and women were similar. Symptoms were more common in men with manual occupations
      than in those with non-manual jobs, but in women there was no clear trend in
      relation to social class. Geographical differences in prevalence were small, but
      the threshold for consulting general practitioners about symptoms varied markedly
      from place to place. After allowance for age, sex, social class, and severity of
      symptoms, subjects in the northern towns of Arbroath and Peterlee who had
      suffered from low back pain in the past year were three to four times as likely
      to have consulted their doctor about the problem as those living in the southern
      towns of St Austell and Dorking. Consultation rates in the Midlands were
      intermediate. CONCLUSIONS: Geographical variation in rates of general practice
      consultation for low back pain in Britain is due largely to differences in
      patient behaviour once symptoms have developed. The distribution of important
      causes of low back back pain across the country is probably fairly uniform.

PMID- 1386620
TI  - Risk of low back pain in people admitted to hospital for traffic accidents and
      falls.
AB  - STUDY OBJECTIVE: The aim was to assess the risk of back symptoms in people
      admitted to hospital because of traffic accidents and falls. DESIGN: The study
      was a cross sectional survey with information collected by postal questionnaire.
      Main outcome measures were associations between hospital admission for a traffic
      accident or fall and reported first onset of back symptoms at the same age and at
      later ages. SETTING: General practices in seven towns and one rural district.
      SUBJECTS: 1172 men and 1495 women aged 20-59 years were selected from the age-sex
      registers of 136 general practitioners in the study areas. MAIN RESULTS: Low back
      pain was reported by 1556 subjects and hospital admission for a traffic accident
      or fall by 362. The incidence of low back pain was unusually high during the year
      of age at which subjects were first admitted to hospital for trauma (RR = 5.5,
      95% CI 3.8-7.8). The risk of first developing symptoms in subsequent years was
      lower, but still significantly increased (RR = 1.3, 95% CI 1.1-1.6). Low back
      pain which started at the age of an accident tended to last longer than that
      occurring in other circumstances, and was more often ascribed to injury (56% of
      cases). However, this proportion was smaller than the calculated attributable
      proportion for traffic accidents and falls (82%). CONCLUSIONS: The data suggest
      that a person under age 60 years who is admitted to hospital for a traffic
      accident or fall has a 7% chance of developing low back pain as result of the
      injury. However, the link between the injury and subsequent symptoms is often not
      obvious to the patient.

PMID- 1386621
TI  - Oral contraceptive use and cardiovascular disease: is the relationship real or
      due to study bias?
AB  - BACKGROUND: Epidemiologic studies link oral contraceptive use with several
      cardiovascular events, but the literature is difficult to summarize, and
      potential biases remain poorly addressed. This study uses meta-analysis to
      summarize study results and to analyze the influence of study characteristics,
      including susceptibility to bias, on study outcome. METHODS: Forty-seven case
      control and cohort studies of oral contraceptives and four cardiovascular events
      were coded for relative risk (RR) and study characteristics, including adherence
      to 14 bias-control standards. Key RRs were pooled to summarize findings for each
      disease type. Univariate determinants of the magnitude of the relative risks were
      identified, and partial correlation analysis was performed for each disease type.
      RESULTS: Relative risks were significantly greater than 1.0 for venous
      thromboembolism (RR = 2.8, CI = 2.4 to 3.2), stroke (RR = 1.8, CI = 1.6 to 2.0),
      and myocardial infarction (RR = 1.6, CI = 1.4 to 1.8), but not for death due to
      any cardiovascular cause (RR = 1.0, CI = 0.8 to 1.3). Study characteristics were
      diverse, and potential biases were frequently uncontrolled. For three of ten
      study characteristics identified as independently influencing relative risk,
      methodologically stronger studies of venous thromboembolism tended to have higher
      RRs. The RRs for stroke and myocardial infarction were lower in studies that were
      methodologically stronger with regard to variables identified as important. In
      studies of cardiovascular death, bias-control standards identified as important
      were generally well addressed by the studies. CONCLUSIONS: Oral contraceptive use
      does not appear to increase overall cardiovascular mortality. The associations
      noted with stroke and myocardial infarction may be due to methodologic flaws in
      the studies, while the association with venous thromboembolism is more likely to
      be valid.

PMID- 1386622
TI  - Typing of human red cell and serum mixtures in three electrophoretic systems.
AB  - The isoenzymes erythrocyte acid phosphatase and phosphoglucomutase were typed in
      mixed red cell samples which had been derived from two individuals; the protein
      group specific component was typed in mixed serum samples. Typing was performed
      by isoelectric focusing on ultrathin polyacrylamide gels. Depending upon the
      mixture, from 2 to 20% (but typically 5-10%) by volume of a second blood or serum
      needed to be present in a mixture before it could be detected. In the majority of
      cases when there was significant mixing, samples were readily identified as a
      mixture when the results consisted of unusual band patterns or unusual band
      intensities. There would be a few instances when blood or serum could not be
      identified as a mixture when masking effects occurred or when the mixture
      produced a combined, apparently normal, pattern.

PMID- 1386624
TI  - Postsynaptic, but not presynaptic, activity controls the early time course of
      long-term potentiation in the dentate gyrus.
AB  - The early time course (less than 1 hr) of long-term potentiation (LTP) in the
      dentate gyrus of the guinea pig hippocampal slice was examined using
      extracellular recordings from the outer two-thirds of the dendritic layer. LTP
      was induced by a single brief (2-40 impulses) high-frequency (20-400 Hz) train,
      or by pairing a single test stimulus with a brief heterosynaptic high-frequency
      train. The induction of LTP was facilitated by blockade of fast GABAergic
      postsynaptic inhibition. It was found that, irrespective of induction conditions
      and the amount of LTP induced, the onset of LTP was characterized by a latency of
      a few seconds following the induction event, and a rapid 30 sec growth phase.
      After a 1-2 min period of little or no further growth, LTP decayed but in a
      highly variable manner, from cases in which more than 60% of the peak value
      remained 1 hr after the induction to cases in which LTP decayed completely within
      10 min. Factors increasing presynaptic activity (frequency or number of afferent
      stimulations) during the induction event did not affect the relative amount of
      LTP decay. Repetitive presynaptic activity was found not to be a necessary
      condition for eliciting long-lasting LTP (greater than 1 hr), as shown by
      experiments in which a single presynaptic impulse was paired with a brief
      heterosynaptic train. Factors increasing postsynaptic activity during the
      induction event, such as increased stimulus intensity, temporal pairing of two
      weak trains, or reduced postsynaptic inhibition, all reduced the relative amount
      of LTP decay. Moreover, partial pharmacological blockade of NMDA receptor
      channels increased the relative amount of decay. In conclusion, the amount of
      postsynaptic activity and associated NMDA receptor activation during the
      induction event appeared to be the main factor governing the early stability of
      LTP in the dentate gyrus.

PMID- 1386623
TI  - Interactions between phospholipase C-coupled and N-methyl-D-aspartate receptors
      in cultured cerebellar granule cells: protein kinase C mediated inhibition of N
      methyl-D-aspartate responses.
AB  - The N-methyl-D-aspartate (NMDA) receptor of rat cerebellar granule cells in
      primary culture is inhibited by phospholipase C-coupled receptor activation. In
      the absence of ionotropic agonist, cells modulate their cytoplasmic free Ca2+,
      [Ca2+]c, in response to stimulation of M3 muscarinic receptors, metabotropic
      glutamate receptors, and endothelin receptors by the respective agonists
      carbachol, trans-1-amino-1,3-cyclopentanedicarboxylic acid, and endothelin-1. The
      response is consistent with the ability of phospholipase C-coupled receptors to
      release a pool of intracellular Ca2+ and induce a subsequent Ca2+ entry into the
      cell; both of these responses can be abolished by discharge of internal Ca2+
      stores with low concentrations of ionomycin or thapsigargin. In the case of cells
      stimulated with NMDA, the [Ca2+]c response to the phospholipase C-coupled
      agonists is complex and agonist dependent; however, in the presence of ionomycin
      each agonist produces a partial inhibition of the NMDA component of the [Ca2+]c
      signal. This inhibition can be mimicked by the protein kinase C activator 4 beta
      phorbol 12,13-dibutyrate. It is concluded that NMDA receptors on cerebellar
      granule cells are inhibited by phospholipase C-coupled muscarinic M3,
      glutamatergic, and endothelin receptors via activation of protein kinase C.

PMID- 1386625
TI  - Lumbar support belts.

PMID- 1386626
TI  - Techno-stress. A psychophysiological study of employees with VDU-associated skin
      complaints.
AB  - Little is known about the causes of health complaints associated with work with
      video display units (VDUs). The symptoms are to a large degree similar to those
      of "multiple chemical sensitivity." We observed 47 white-collar employees with
      and without VDU-associated skin complaints during a regular workday and a day of
      leisure. VDU workers with skin symptoms had higher levels of the stress-sensitive
      hormones thyroxin and prolactin compared with employees without symptoms. They
      also had lower levels of the anabolic hormone testosterone during work. VDU
      workers with skin complaints also reported more occupational mental strain. A
      model is proposed in which physiological signals act as unconditioned stimuli and
      the VDU environment as the conditioned stimuli.

PMID- 1386627
TI  - State of the art: regional anesthesia using anesthetic admixtures.
AB  - Aging, high-risk, and ambulatory patients comprise a growing population of
      surgical candidates. The advantages of regional anesthesia for these patients has
      promoted technological and pharmacological advances. As new anesthetic agents are
      developed, methods to improve existing local anesthetics continue. This article
      reviews the current practice of local anesthetic admixtures. The physiological
      action of the local anesthetics and their additives is explained relative to
      their chemical properties. The advantages and risks when adding bicarbonate and
      epinephrine are described. Nursing implications for the care of the patient
      receiving regional anesthesia using admixtures are reviewed. An actual case
      report is presented to demonstrate the clinical application of local anesthetic
      admixtures.

PMID- 1386628
TI  - From theory to practice: Orem's self-care nursing model and ambulatory care.
AB  - Delivery of patient care based on theoretical principles can promote successful
      practice. Orem's Self-Care Nursing Theory offers direction for the practitioner
      in the ambulatory surgery setting. In this model, the nurse assists clients by
      acting for, teaching, guiding, supporting, and providing a developmental
      environment. Levels of care range from performing total care to educating the
      patient and family. Promoting self-care as soon as feasible is the goal of the
      ambulatory care plan. Consequently, self-care deficits created during surgery and
      anesthesia must be overcome so that the patient is dismissed from the ambulatory
      setting with the ability to meet self-care needs.

PMID- 1386629
TI  - Telephone follow-up of ambulatory surgery patients following discharge is a
      nursing responsibility.
AB  - The ambulatory surgery nurse manages care for a diverse population of patients
      who may or may not be ideal candidates for early discharge after surgery.
      Integral to the nursing care is the postdischarge follow-up contact, which allows
      the nurse to assess the patient's level of recuperation and evaluate the care
      provided. A number of reasons, besides completion of the nursing process,
      indicate that this contact is a nursing obligation. These include compliance with
      national standards of care, improvement of quality of care, and reduction of the
      facility's liability exposure. These calls also show a sense of caring about
      patients and help to market the ambulatory surgery program in the community. The
      nurse develops a true sense of professionalism and often benefits by increased
      job satisfaction.

PMID- 1386630
TI  - Practical points in the management of a postoperative acoustic neuroma patient.
AB  - Presented in this article is a brief overview of cranial anatomy and
      pathophysiology. Highlights of preoperative signs and symptoms and three surgical
      procedures performed on acoustic neuroma patients are discussed. Postoperative
      complications and nursing interventions are emphasized.

PMID- 1386631
TI  - Concept analysis methodology: applications to altered level of consciousness.
AB  - Concept analysis is the first step in instrument development. Steps in the
      concept analysis process are discussed and applied to the analysis of altered
      level of consciousness (ALC) as a potential nursing diagnosis for submission to
      the North American Nursing Diagnosis Association. Criteria regarding ALC have
      been defined for the assessment of neurologically impaired patients and not for
      the neurologically intact postanesthesia patient. It is assumed that
      postanesthesia patients experience chemically induced ALC, and consensus
      regarding what constitutes this concept needs to be validated by PACU nurses. The
      first step in instrument development is a clear definition of the concept of
      interest. The criteria for ALC determined by the PACU nurses could then be used
      to construct a pencil-and-paper instrument that would allow the concept to be
      tested on postanesthesia patients as they emerge from anesthesia. This concept
      analysis-to-instrument development process discussion can be applied to any
      concept of interest to the PACU nurse.

PMID- 1386632
TI  - Traumatic neuropathic spinal arthropathy.
AB  - Traumatic spinal neuropathy is a condition which results as a loss of the
      feedback response from the insensate spine. Clinically a severe kyphotic
      deformity and gross instability is apparent. Radiographically, severe joint
      destruction with a "ball and socket" pseudarthrosis is seen. An infectious
      process must be excluded and surgical stabiliation has an excellent prognosis.

PMID- 1386633
TI  - Thymopentin in Sezary syndrome.
AB  - BACKGROUND: Response to the treatment of Sezary syndrome (a cutaneous T-cell
      lymphoma) is poor. Since patients with this syndrome are elderly, aggressive
      chemotherapy is poorly tolerated and deep immunodepression may result in fatal
      opportunistic infections. Immunomodulating therapy seems important in the
      management of Sezary syndrome. PURPOSE: In a pilot study, we assessed the
      efficacy of thymopentin (TP-5), a synthetic pentapeptide, correlating clinical
      responses to the histologic and immunologic effects of the drug. METHODS: Twenty
      Sezary syndrome patients received 50 mg TP-5 intravenously three times a week for
      a mean time of 16.3 months. Skin and lymph node histology and
      immunohistochemistry, circulating lymphoid cell subpopulations, and soluble
      interleukin-2 receptors were evaluated before treatment and during follow-up.
      RESULTS: Eight complete remissions and seven partial remissions were obtained
      (75%). No change was observed in three patients, and disease progression was
      observed in two patients. The median duration of response was 22 months (complete
      remission, 25.5 months; partial remission, 14 months). Four-year survival
      probability was 53.9%. The responses were obtained when circulating Sezary cells
      were less than 2600/mm3. A significant reduction of CD4+ cells paralleled a CD8+
      cell increase. An increase in NK cells (CD16+ and CD56+) was accompanied by
      significantly longer survival. Serum soluble interleukin-2 receptor values were a
      useful monitor of the clinical course and treatment. Loss of epidermotropism,
      reduction of Langherhans' cells, and HLA-DR+ keratinocytes were found.
      CONCLUSIONS: TP-5 is a potentially useful agent in the treatment of a subgroup of
      patients with Sezary syndrome; its activity seems to be mediated by an effect on
      a normal NK cell-like subpopulation. IMPLICATIONS: The biological and clinical
      role of this therapy in combination with conventional treatments will be the
      subject of future investigations.

PMID- 1386634
TI  - Dapsone syndrome in Vanuatu: a high incidence during multidrug treatment (MDT) of
      leprosy.
AB  - Side-effects of leprosy treatment with dapsone are said to be uncommon, with drug
      allergy occurring in only one of every several hundred patients treated with
      dapsone. The dapsone or sulphone syndrome (DDS) has been recognized since the
      earliest days of sulphone therapy but until recently its incidence had been
      decreasing. In Vanuatu, during the years 1988-1991, nine leprosy patients have
      developed the dapsone syndrome, four of whom have died. During the last 4 years
      only 37 patients were started on treatment, which is an incidence of the dapsone
      syndrome of 24% with a fatality rate of 11%. All the patients were being given
      multi-drug treatment (MDT) of daily dapsone (100 mg) and clofazimine (50 mg) and
      monthly rifampicin (600 mg) and clofazimine (300 mg). There has been speculation
      that the increased incidence of what was previously described as a rare reaction
      is due to the use of MDT, and the reasons for this are discussed. We feel the
      increase in the number of reactions in Vanuatu since starting MDT is probably due
      to the high starting dose of 100 mg of dapsone, possibly enhanced by the
      combination with clofazimine and rifampicin and a genetic susceptibility of the
      Melanesian population.

PMID- 1386635
TI  - Correlation of inflammatory infiltrate with the enlargement of experimental
      aortic aneurysms.
AB  - Inflammatory cells often are seen in the walls of human aortic aneurysms, but
      their significance is uncertain. To investigate their actions an in vivo model of
      arterial aneurysms was developed in the rat. Fifteen units of hog pancreatic
      elastase were infused for 2 hours into the isolated abdominal aorta in 26 rats.
      The vessels were measured in vivo and were excised for conventional histologic
      and immunohistologic study at selected intervals. In untreated control rats the
      diameter of the aorta was 1.04 +/- 0.02 mm. Immediately after infusion with
      elastase the aorta dilated 26% to 1.31 +/- 0.02 mm (p = NS), with no
      histologically demonstrable remaining elastic lamellae. Two and one half days
      after infusion the aorta dilated nearly 300% to 3.09 +/- 0.08 mm (p less than
      0.05). These vessels exhibited large numbers of activated macrophages and T cells
      in the media. Three and 4 days after infusion the vessels dilated 388% to 4.04 +/
      0.09 mm and 367% to 3.82 +/- 0.31 mm, respectively. These vessels also exhibited
      numerous inflammatory cells in the media. Six days after infusion the vessels
      enlarged 421% to 4.38 +/- 0.03 mm (p less than 0.05), and the infiltrate
      persisted staining immunohistologically for macrophages, polymorphic neutrophils,
      and T lymphocytes. Twelve days after infusion the aneurysms remained enlarged but
      stable at 4.23 +/- 0.14 mm (p = NS). At this time the number of inflammatory
      cells regressed to control levels. The temporal correlation between inflammatory
      infiltrate and aneurysmal enlargement suggests that inflammatory cells may
      participate in the destruction of the aneurysmal vessel wall thereby promoting
      progressive enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386636
TI  - Functional and metabolic responses to ischemia in the isolated perfused
      hypothyroid rat heart.
AB  - It has been demonstrated that the V3 cardiac myosin isozyme has a higher
      efficiency and consumes less oxygen in doing mechanical work than the V1 myosin
      isozyme. The purpose of the present study is to investigate the functional and
      metabolic responses to ischemia following reperfusion of the hypothyroid heart,
      in which ventricular myosin isozyme is shifted from V1 predominance to V3
      predominance. The heart was perfused by the working heart method for 15 min, and
      then global ischemia was induced for 10, 20 and 30 min with pacing at a rate of
      320/min until cardiac cessation. The ischemic heart was reperfused for 30 min.
      The extent of recovery of pressure-rate product after reperfusion, following 20
      min of ischemia in the hypothyroid heart, was higher than that in the control
      heart (p less than 0.01). The level of adenosine triphosphate (ATP) declined more
      slowly in the hypothyroid heart than in the control heart. The level of ATP and
      energy charge potential in the hypothyroid heart reperfused after 20 min of
      ischemia were higher than those in the reperfused control heart (p less than
      0.01, p less than 0.05, respectively), though they did not differ from each other
      in preischemia. There were no significant differences in the levels of tissue
      lactate between the 2 hearts during ischemia and reperfusion. The recovery rate
      of the coronary flow of the 2 hearts did not differ from each other
      significantly. These data suggest that there is probability of the V3 predominant
      heart recovering from ischemic damage to the metabolism and cardiac function
      better than the V1 predominant heart because the transformation of myocardium,
      due to an increase in V3 into a slower but more efficiently working muscle
      results in conservation of tissue ATP during ischemia.

PMID- 1386637
TI  - Molecular mechanism of hypertrophied failing heart--abnormalities of the
      diastolic properties and contractility.
AB  - The clinical syndrome of heart failure occurs as a consequence of the limitation
      of compensatory mechanisms, such as cardiac hypertrophy. To clarify
      transcriptional changes in specific genes in failing hearts, we examined the
      expression of cardiac Ca(2+)+Mg(2+)-dependent ATPase in the sarcoplasmic
      reticulum and transforming growth factor beta genes in the ventricles of rat
      hypertrophied heart, and the expression of guanine nucleotide-binding protein and
      "fetal" contractile protein genes in the ventricles of cardiomyopathic Syrian
      hamsters of Bio14.6. Northern blot analysis of total cellular RNA revealed that
      the mRNA levels of Ca(2+)+Mg(2+)-dependent ATPase were decreased by pressure
      overload and became 32% of sham in 1 month, and were correlated with
      corresponding protein levels. Transforming growth factor beta mRNA, a potent
      activator of collagen synthesis, was increased by pressure overload. The
      expression levels of the Gs alpha mRNA, which stimulated the adenylate cyclase,
      in Bio14.6 ventricles were lower than the levels in ventricles of the F1B hamster
      strain, and decreased as the stage of cardiomyopathy progressed. Moreover, re
      expression of fetal mRNA was observed in the ventricle of cardiomyopathic Syrian
      hamsters of the Bio14.6 strain. These results indicate that reprogramming of
      cardiac gene expression both of myofibrillar and nonmyofibrillar components might
      occur in the failing heart.

PMID- 1386638
TI  - [Comments on a letter].

PMID- 1386639
TI  - Augmentation of interleukin-2 production after cardiac operations in patients
      treated with erythropoietin.
AB  - It has been reported recently that cardiac operations can be followed by a
      transient impairment of cell-mediated immunity. In this study we examined indices
      of cell-mediated immunity in patients undergoing cardiac operations. Twenty-five
      of the patients received erythropoietin (200 U/kg) daily for 2 weeks before and
      after operation, and 30 matched control patients did not receive erythropoietin.
      On postoperative day 1, the numbers of total T cells and helper/inducer T cells
      were significantly higher in erythropoietin-treated patients than in control
      patients. The ability of patients' cells to make interleukin-2 in vitro increased
      after erythropoietin injection in the preoperative period. By postoperative day
      1, erythropoietin-treated patients exhibited a fall in interleukin-2 production
      that was significantly less than that in control patients; levels increased by
      day 2 to a mean value twice that of the preoperative baseline and more than four
      times the corresponding mean level in the control groups, and levels returned to
      the baseline range by postoperative day 14. Levels of interleukin-2 production in
      erythropoietin-treated patients were significantly higher than those in control
      patients at each interval tested through postoperative day 7. These findings
      indicate that erythropoietin treatment not only augmented levels of circulating
      erythrocytes but also improved indices of cell-mediated immunity. Although the
      mechanism responsible for this effect remains to be determined, the finding
      suggests that erythropoietin might help to ameliorate or prevent the impairment
      of immune function that can occur after cardiac operations.

PMID- 1386641
TI  - Treatment of acute pain with auricular pellet pressure on ear shenmen as the main
      point.

PMID- 1386640
TI  - Warm retrograde cardioplegia. Protection of the right ventricle in mitral valve
      operations.
AB  - Hypothermia is believed to be the most important aspect of successful myocardial
      protection with retrograde coronary sinus cardioplegia. Because nutritive
      capillary flow to the right ventricle and septum is thought to be diminished with
      retrograde perfusion, these areas of the myocardium are considered at higher risk
      for intraoperative deterioration without the added protection of hypothermia.
      Recently we introduced warm aerobic arrest as an alternative to conventional
      methods of myocardial protection. We present our clinical results in 37 patients
      with mitral valve disease (+/- aortic valve, aortic root, or coronary artery
      disease) who underwent various cardiac procedures for which warm blood
      cardioplegic solution was delivered continuously via the coronary sinus after
      antegrade arrest. Thirty-five of the patients were in New York Heart Association
      class III or IV, and 19 patients had grade 3 or grade 4 left ventricular
      function. Sixteen patients had pulmonary hypertension, three with suprasystemic
      pressures, and marked right ventricular hypertrophy. Two patients had associated
      left ventricular hypertrophy. Nearly all patients returned to normal sinus rhythm
      shortly after removal of the aortic crossclamp, and they were easily discontinued
      from cardiopulmonary bypass even with crossclamp times of 3 hours. The 30-day
      hospital mortality rate was 2.7%. The perioperative myocardial infarction rate
      was 5.4%, and the prevalence of low-output syndrome was 10.8%. The results
      suggest that retrograde coronary sinus perfusion of blood cardioplegic solution
      at 37 degrees C is an effective method of myocardial protection even in patients
      with pulmonary hypertension at high risk for right ventricular failure. Its
      efficacy in this circumstance does not reside in its ability to deliver
      hypothermia.

PMID- 1386642
TI  - Innervation of the paralyzed laryngeal muscles by phrenic motoneurons. A
      quantitative study by light and electron microscopy.
AB  - In the cat, inspiratory opening of the paralyzed glottis recovered after
      unilateral or bilateral reinnervation of the posterior cricoarytenoid (PCA)
      muscles by phrenic axons. The morphometric analysis of the regenerated recurrent
      laryngeal nerves (RLNs), showed that proliferation was abundant; 4 months after
      the nerve anastomosis, more than 500 myelinated axonal branches repopulated the
      RLNs. The mean diameter of motor axons (3.5 to 5.0 microns) was lower than in
      normal phrenic and RLN (8 to 10 microns), and the mean internode length was about
      half that of the normal RLN. Histochemical examination of the PCA muscle revealed
      that muscle fiber composition (44% type I and 56% type II muscle fiber) was
      fairly similar to that of normal PCA. The contraction time of the reinnervated
      muscles was as long as 60 msec at the time of movement recovery, but it shortened
      to 25 to 30 msec when the reinnervation time increased. These anatomical and
      functional results support the choice of the phrenic nerve for laryngeal
      reinnervation.

PMID- 1386643
TI  - Use of the holmium:YAG laser in urology.
AB  - The tissue effects of a holmium:YAG (Ho:YAG) laser operating at a wavelength of
      2.1 mu with a maximum power of 15 watts (W) and 10 different energy-pulse
      settings was systematically evaluated on kidney, bladder, prostate, ureteral, and
      vasal tissue in the dog. In addition, various urologic surgical procedures
      (partial nephrectomy, transurethral laser incision of the prostate, and laser
      assisted vasovasostomy) were performed in the dog, and a laparoscopic pelvic
      lymph node dissection was carried out in a pig. Although the Ho:YAG laser has a
      strong affinity for water, precise tissue ablation was achieved in both the
      contact and non-contact mode when used endoscopically in a fluid medium to ablate
      prostatic and vesical tissue. Using the usual parameters for tissue destruction
      (blanching without charring), the depth of thermal injury in the bladder and
      ureter was kept superficial. In performing partial nephrectomies, a 2-fold
      reduction in the zone of coagulative necrosis was demonstrated compared to the
      use of the continuous wave Neodymium:YAG laser (Nd:YAG). When used through the
      laparoscope, the Ho:YAG laser provided precise cutting and, combined with
      electrocautery, allowed the dissection to proceed quickly and smoothly.
      Hemostatic control was adequate in all surgical procedures. Although the results
      of these investigations are preliminary, our initial experience with the Ho:YAG
      laser has been favorable and warrants further investigations.

PMID- 1386644
TI  - In vitro laser recanalization of chronically occluded prosthetic grafts.
AB  - Polytetrafluoroethylene (PTFE) and Dacron grafts were implanted in canine femoral
      and carotid arteries using PTFE and Prolene suture, respectively. Arteries
      containing occluded grafts were explanted and laser recanalization was attempted
      in vitro. Laser recanalization was successful in 78% of PTFE grafts compared to
      30% of Dacron grafts. Recanalization was complete (residual stenosis less than
      5%) in opened PTFE grafts, whereas residual stenosis averaged 60% in recanalized
      Dacron grafts. PTFE graft/PTFE suture anastomotic tensile strength was unchanged
      after recanalization, while Dacron graft/Prolene suture anastomotic tensile
      strength decreased significantly. In addition, anastomotic bursting pressure was
      significantly higher for lased PTFE grafts with PTFE sutures (300 mg Hg) compared
      to lased Dacron grafts with Prolene sutures (70 mm Hg). Chronically occluded PTFE
      grafts with PTFE suture can be safely and effectively opened by laser
      recanalization. In contrast, attempted laser recanalization of Dacron grafts
      sutured with Prolene suture is seldom successful, significantly weakens the graft
      artery anastomosis, and should be avoided.

PMID- 1386645
TI  - Escherichia coli integration host factor stabilizes bacteriophage Mu repressor
      interactions with operator DNA in vitro.
AB  - Using gel retardation and DNase I protection techniques, we have demonstrated
      that the Escherichia coli integration host factor (IHF) stabilizes the
      interaction between Mu repressor and its cognate operator-binding sites in vitro.
      These results are discussed in terms of a model in which IHF may commit the phage
      to the lytic or lysogenic pathway depending on the occupancy of the operator
      sites by the repressor.

PMID- 1386646
TI  - Stabilization of bacteriophage Mu repressor-operator complexes by the Escherichia
      coli integration host factor protein.
AB  - All of the previously described effects of integration host factor (IHF) on
      bacteriophage Mu development have supported the view that IHF favours
      transposition-replication over the alternative state of lysogenic phage growth.
      In this report we show that, consistent with a model in which Mu repressor
      binding to its operators requires a particular topology of the operator DNA, IHF
      stimulates repressor binding to the O1 and O2 operators and enhances Mu
      repression. IHF would thus be one of the keys, besides supercoiling and the H-NS
      protein, that lock the operator region into the appropriate topological
      conformation for high-affinity binding not only of the phage transposase but also
      of the phage repressor.

PMID- 1386647
TI  - [Fungal infections in the human. 3: Nail mycoses].

PMID- 1386648
TI  - Mivacurium--a new neuromuscular blocker.

PMID- 1386649
TI  - Characterization of a non-tissue-specific, 3',5'-cyclic adenosine monophosphate
      responsive element in the proximal region of the rat prolactin gene.
AB  - The nature of a DNA element located in the -100 to -85 region of the rat PRL gene
      has been characterized. Previous studies demonstrated that this region may
      contribute to basal and hormonally regulated expression of the PRL gene. As this
      region contains a sequence with similarity to a consensus cAMP-responsive element
      (CRE), a possible role for the cAMP response element binding protein (CREB) has
      been explored. A point mutation which made the PRL CRE-like sequence less like a
      consensus CRE had little effect on basal or cAMP-stimulated expression of a PRL
      luciferase reporter gene. DNase footprint studies demonstrated that the proximal
      region of the PRL gene does not contain a high affinity CREB binding site.
      Mobility shift experiments demonstrated that the major GH3 nuclear protein which
      interacts with the -100 to -85 region of the PRL gene in vitro is not CREB.
      Transfection of a dominant inhibitor of CREB action had little or no effect on
      expression of an indicator gene containing the PRL proximal region. Thus, the PRL
      proximal region does not contain a high affinity CREB binding site, and it is
      unlikely that CREB plays a major role in expression of the PRL gene. The
      functional capabilities of the -100 to -85 region of the PRL gene were then
      tested in a transfection assay. Synthetic multimers of this region were found to
      be sufficient to permit a transcriptional response to cAMP or TRH in GH3 cells
      and cAMP in Rat-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386650
TI  - The human mast cell receptor binding site maps to the third constant domain of
      immunoglobulin E.
AB  - The characterization of the site on the IgE molecule which accommodates the high
      affinity receptor for IgE (Fc epsilon RI) should allow the design of IgE
      analogues which can be utilized to block allergic responses. Using chimeric human
      IgE molecules in which different constant region domains were exchanged with
      their murine homologues, we demonstrate here that the C epsilon 3 in its native
      configuration is essential for the binding to the alpha subunit of the human Fc
      epsilon RI. Deletion of the human C epsilon 2 from such chimeric molecules did
      not impair their ability to interact with the Fc epsilon RI, indicating that C
      epsilon 2 is not directly involved in the human Fc epsilon RI binding site and
      that C epsilon 3 alone is necessary and sufficient to account for most of the
      human Fc epsilon RI-binding capacity.

PMID- 1386651
TI  - The human T cell receptor gamma genes are transcribed from TATA-less promoters
      containing a conserved heptamer sequence.
AB  - We have used the anchored polymerase chain reaction (A-PCR) to clone and compare
      the 5' upstream regions of the human T cell receptor gamma (TRG) genes. Whereas
      little homology was found among subgroups I, II, III and IV, sequence alignment
      of TRG subgroup I members revealed a high degree of homology in the 5' sequences.
      A conserved heptamer sequence (CTGCAGG), which was found upstream from the
      translation initiation site of all TRG genes in our analysis. Determination of
      the transcription initiation site located the conserved heptamer 65 base pairs
      upstream from the cap sites of V5. No TATA box or other cis-acting promoter
      sequences could be identified in any of the human TRG upstream sequences.

PMID- 1386652
TI  - Effect of captopril on mortality and morbidity in patients with left ventricular
      dysfunction after myocardial infarction. Results of the survival and ventricular
      enlargement trial. The SAVE Investigators.
AB  - BACKGROUND: Left ventricular dilatation and dysfunction after myocardial
      infarction are major predictors of death. In experimental and clinical studies,
      longterm therapy with the angiotensin-converting--enzyme inhibitor captopril
      attenuated ventricular dilatation and remodeling. We investigated whether
      captopril could reduce morbidity and mortality in patients with left ventricular
      dysfunction after a myocardial infarction. METHODS: Within 3 to 16 days after
      myocardial infarction, 2231 patients with ejection fractions of 40 percent or
      less but without overt heart failure or symptoms of myocardial ischemia were
      randomly assigned to receive doubleblind treatment with either placebo (1116
      patients) or captopril (1115 patients) and were followed for an average of 42
      months. RESULTS: Mortality from all causes was significantly reduced in the
      captopril group (228 deaths, or 20 percent) as compared with the placebo group
      (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent
      confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of
      both fatal and nonfatal major cardiovascular events was consistently reduced in
      the captopril group. The reduction in risk was 21 percent (95 percent confidence
      interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37
      percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for
      the development of severe heart failure, 22 percent (95 percent confidence
      interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring
      hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent;
      P = 0.015) for recurrent myocardial infarction. CONCLUSIONS: In patients with
      asymptomatic left ventricular dysfunction after myocardial infarction, long-term
      administration of captopril was associated with an improvement in survival and
      reduced morbidity and mortality due to major cardiovascular events. These
      benefits were observed in patients who received thrombolytic therapy, aspirin, or
      beta-blockers, as well as those who did not, suggesting that treatment with
      captopril leads to additional improvement in outcome among selected survivors of
      myocardial infarction.

PMID- 1386654
TI  - Morbidity associated with laparoscopic cholecystectomy.

PMID- 1386653
TI  - Identification by mutagenesis of a Mg(2+)-block site of the NMDA receptor
      channel.
AB  - The N-methyl-D-aspartate (NMDA) receptor channel is highly permeable to Ca2+ but
      is blocked by Mg2+ in a voltage-dependent manner. These characteristics are
      essential for the NMDA receptor channel to mediate the induction of long-term
      potentiation of synaptic efficacy, a form of activity-dependent synaptic
      plasticity thought to underlie memory, learning and development. Recent studies
      have revealed the molecular and functional diversity of the NMDA receptor channel
      subunits, which are classified into the epsilon and zeta families according to
      the amino-acid sequence homology. Here we report that replacement by glutamine of
      asparagine 598 in putative transmembrane segment M2 of the zeta 1 subunit,
      strongly reduces the sensitivity of the heteromeric epsilon 2/zeta 1 NMDA
      receptor channel to Mg2+ block. The corresponding mutation of the epsilon 2
      subunit has a similar effect. Furthermore, the heteromeric epsilon 2/zeta 1 NMDA
      receptor channel with the mutation on both subunits shows greatly reduced
      sensitivity to MK-801, a channel blocker of the NMDA receptor channel, but is
      still susceptible to inhibition by Zn2+. These findings suggest that the
      conserved asparagine residue in segment M2 constitutes a Mg(2+)-block site of the
      NMDA receptor channel, and that the MK-801 site overlaps the Mg2+ site.

PMID- 1386655
TI  - Cholesterol lowering--the sense and the sensationalism.

PMID- 1386656
TI  - The identification of spinal pathology in chronic low back pain using single
      photon emission computed tomography.
AB  - Bone scintigraphy with single photon emission computed tomography (SPECT) offers
      improved lesion detection and localization when compared to conventional planar
      imaging. The SPECT findings were investigated in 80 consecutive patients (aged 18
      70 years, median 44) referred to a rheumatology outpatient clinic with low back
      pain persisting for more than 3 months. Lesions of the lumbar spine were
      demonstrated in 60% of patients using SPECT but in only 35% with planar imaging.
      Fifty-one per cent of all lesions were only detected by SPECT, and lesions
      visualized on SPECT could be precisely localized to the vertebral body, or
      different parts of the posterior elements. Fifty per cent of lesions involved the
      facetal joints of which almost 60% were identified on SPECT alone. X-rays of the
      lumbar spine, with posterior oblique views, failed to demonstrate abnormalities
      corresponding to almost all SPECT posterior element lesions although it
      identified abnormalities corresponding to over 60% of anterior SPECT lesions.
      Computed tomography (CT) was performed in 30 patients with a SPECT lesion and
      sites of facetal joint activity corresponded to facetal osteoarthritis in 82%. It
      is concluded that bone scintigraphy with SPECT in patients with chronic low back
      pain demonstrates many lesions not seen with either X-ray or conventional planar
      imaging. In addition anatomical localization is greatly enhanced with bone SPECT.
      The technique offers improved diagnosis in a group of patients often difficult to
      evaluate, and in particular a means of detecting apophyseal joint pathology which
      may be responsive to treatment.

PMID- 1386657
TI  - 123I-methylene blue: an unsatisfactory parathyroid imaging agent.
AB  - This study was designed to examine the possible use of 123I-labelled methylene
      blue as a parathyroid imaging agent. Five patients were studied, all of whom had
      parathyroid adenomas which were successfully localized preoperatively with 201Tl
      and 99Tcm-sestamibi, and which were subsequently proven at surgery. The 123I
      labelled methylene blue localized only one of these adenomas, was negative in two
      and had equivocal uptake in the remaining two patients. It is therefore concluded
      that compared to other radionuclide methods for localizing parathyroid adenomas
      this agent is unsatisfactory.

PMID- 1386658
TI  - Laparoscopic oophorectomy: comparative study of ligatures, bipolar coagulation,
      and automatic stapling devices.
AB  - OBJECTIVE: We assessed laparoscopic oophorectomy using three techniques. METHODS:
      From January 1989 to October 1991, 65 patients underwent laparoscopic
      oophorectomy using three techniques: bipolar coagulation, pretied ligature
      placement, and automatic stapling devices. The patients were aged 18-57 years and
      had the indications of pain, ovarian endometriosis, adhesions, unilateral blocked
      tubes, breast cancer, and recurrent benign ovarian cysts. The primary method of
      adnexal removal involved the automatic stapling device in 17, bipolar coagulation
      in 30, and pretied ligatures in 18. RESULTS: Total anesthesia time ranged from 45
      123 minutes, with means of 77 minutes for pretied ligatures, 84 minutes for
      bipolar coagulation, and 84 minutes for automatic stapling devices. Sixty-two
      patients were discharged within 23 hours, two stayed two nights, and one stayed
      three nights. Rectus muscle bleeding and hematoma formation were the only
      complications in this series. CONCLUSION: All three methods of laparoscopic
      oophorectomy are effective, with similar operative times and uniformly good
      results for the patients.

PMID- 1386659
TI  - Expectant management of ectopic pregnancy.
AB  - OBJECTIVE: To evaluate expectant management in selected cases of ectopic
      pregnancy. METHODS: Transvaginal sonography and estimation of serum hCG
      concentrations were used in the evaluation and follow-up of ectopic pregnancy.
      Entry criteria for expectant management were: decreasing level of serum hCG,
      diameter of the ectopic pregnancy less than 4 cm, and no signs of rupture or
      acute bleeding by vaginal sonography. RESULTS: Expectant management was studied
      in 83 patients, representing 26% of all ectopic pregnancies during a 2-year
      period. In 57 patients (69%), spontaneous resolution occurred, corresponding to
      18% of all ectopic pregnancies. Laparoscopy was performed in 26 because of
      clinical symptoms or a rise in hCG level after expectant management for 1-18
      days. One patient had a tubal rupture requiring tubal resection by laparoscopy.
      No serious complications occurred. With increasing experience, the rate of
      expectant management and spontaneous resolution increased during study period.
      CONCLUSION: Expectant management with repeated vaginal sonography and estimations
      of serum hCG concentrations is a useful form of treatment for ectopic pregnancy
      in selected cases.

PMID- 1386660
TI  - Ultrasonographic measurements of fetal ear.
AB  - OBJECTIVE: To establish nomograms of fetal ear measurements. Newborns with
      trisomies have smaller ears than the normal population. This observation led us
      to believe that ear measurements might be useful in the antenatal prediction of
      fetuses with abnormal karyotypes. METHODS: Fetal ear length and width were
      obtained ultrasonographically in 124 normal singleton pregnancies between 18-42
      weeks' gestation. Regression analyses were used to create the nomograms. RESULTS:
      Linear relationships were found between ear length and width and gestational age
      (r = 0.956 and 0.898, respectively). In addition, there were significant
      correlations between ear measurements and biparietal diameter, head
      circumference, abdominal circumference, and femur length. The ear width-length
      ratio and the biparietal diameter-ear length ratio were independent of
      gestational age. CONCLUSION: These normative data may be helpful in the antenatal
      prediction of chromosomal abnormalities.

PMID- 1386661
TI  - The laser-assisted scalpel: initial clinical evaluation of its use in gynecologic
      endoscopy.
AB  - The laser-assisted scalpel is a new disposable laparoscopic instrument that
      improves the precision and control of fiberoptic laser energy delivery and
      provides a means of tactile probing and blunt tissue dissection. The instrument
      simplifies laparoscopic technique by providing the surgeon with the ability to
      place tissue under tension when firing the laser, thus minimizing the need to
      exchange instruments. We describe the use and our impressions of the laser
      assisted scalpel for six common human laparoscopic gynecologic procedures
      performed in 68 patients.

PMID- 1386662
TI  - Limb-body wall complex associated with cocaine abuse: further evidence of
      cocaine's teratogenicity.
AB  - Limb-body wall complex is a complicated fetal malformation with the essential
      features of body wall disruption and limb abnormalities. Data from studies in the
      rat model suggest that vascular disruption is an etiology for limb-body wall
      complex. Because of its vasospastic properties, cocaine can act as a teratogen by
      impairing uteroplacental fetal blood flow during critical periods of development.
      We describe the prenatal detection of two fetuses with limb-body wall complex,
      whose mothers smoked large amounts of cocaine during the first trimester of
      pregnancy. Ultrasonographic evaluation of the fetus should be offered routinely
      in pregnancies complicated by maternal cocaine abuse.

PMID- 1386663
TI  - Body stalk anomaly: congenital absence of the umbilical cord.
AB  - On ultrasound examination, a 20-year-old pregnant woman was found to have a fetus
      with a large ventral abdominal wall defect diagnosed as a fetal omphalocele. The
      neonate was delivered by cesarean; the abdominal viscera including liver,
      stomach, spleen, pancreas, intestine, and uterus were contained in an
      extraembryonic sac directly attached to the placenta without an umbilical cord.
      Body stalk anomaly (also known as absence of the umbilical cord syndrome) is a
      fatal condition resulting from maldevelopment of embryonic body folding and is
      associated with multiple congenital defects. Prenatal ultrasonographic
      recognition of the absence of an umbilical cord and direct apposition of the
      membranous sac to the amniochorionic membrane would permit early termination of
      pregnancy or avoidance of operative intervention.

PMID- 1386664
TI  - Laparoscopic oophoropexy for preservation of ovarian function before pelvic node
      irradiation.
AB  - Pelvic irradiation for the treatment of Hodgkin disease in premenopausal women
      invariably results in ovarian failure unless the ovaries are shielded.
      Oophoropexy by laparotomy has been used previously to move the ovaries away from
      the pelvic nodal areas. We have designed, and used in one patient, a new
      laparoscopic technique that can be performed as an outpatient procedure and that
      allows radiation therapy to begin immediately. Oophoropexy was performed
      laparoscopically with placement of sutures through the utero-ovarian ligaments
      and posterior uterus. Surgical clips were placed to help identify the position of
      the ovaries postoperatively.

PMID- 1386665
TI  - Laparoscopic repair of ureter resected during operative laparoscopy.
AB  - Ureteral injury is a recognized complication of gynecologic surgery. During
      operative laparoscopy performed to treat extensive endometriosis of the pelvic
      sidewall, a 1.5-cm portion of the right ureter was resected and was repaired
      successfully. Repair of a resected ureter may be effectively accomplished
      endoscopically by experienced operative laparoscopists.

PMID- 1386666
TI  - Uterine dehiscence following laparoscopic myomectomy.
AB  - BACKGROUND: Laparoscopic myomectomy is a new procedure that is growing in
      popularity. The natural history of pregnancy following laparoscopic myomectomy is
      unknown. CASE: A 24-year-old white woman, gravida 0, with infertility and
      endometriosis, conceived after a laparoscopic procedure that included myomectomy.
      At 34 weeks' gestation, the patient experienced uterine dehiscence at the site of
      myomectomy. An emergency cesarean delivery was performed and the uterus was
      oversewn. Both mother and infant had satisfactory hospital courses. CONCLUSION:
      Meticulous closure of the myometrial bed following myomectomy is difficult via
      the laparoscope, and this could interfere with the integrity of the scar. If
      further studies confirm this experience, then laparoscopic myomectomy may need to
      be limited to patients who do not desire further childbearing.

PMID- 1386668
TI  - [Evidence of pathology in the history of the representational arts].

PMID- 1386667
TI  - [In vitro activity of vancomycin and teicoplanin against gram-positive cocci].
AB  - The activities of vancomycin and teicoplanin against 148 strains of Gram-positive
      cocci were tested using agar diffusion and liquid microdilution MIC
      determination. Tested strains included 84 staphylococci, 32 S. aureus, 52
      coagulase-negative staphylococci (CNS), 52 enterococci, and 12 streptococci. Most
      strains (136) were susceptible to both agents, with inhibition diameters of 17 mm
      or more. MRSA strains exhibited lower geometric MIC means with teicoplanin (0.90
      micrograms/ml) than with vancomycin (1.79 micrograms/ml); this difference was
      found for methicillin-susceptible S. aureus strains (1.07 and 1.38 micrograms/ml
      for teicoplanin and vancomycin, respectively). In contrast, methicillin
      susceptible and methicillin-resistant strains of CNS exhibited similar MICs (1.60
      micrograms/ml approximately). Enterococci were more susceptible to teicoplanin
      (MIC 0.25 micrograms/ml) than to vancomycin (MIC 1.35 micrograms/ml). Both
      vancomycin and teicoplanin were thus found to be consistently effective against
      Gram-positive cocci; however, teicoplanin proved more effective than vancomycin
      against enterococci and methicillin-resistant S. aureus strains and may therefore
      be a valuable therapeutic alternative for these multiresistant organisms.

PMID- 1386669
TI  - Characteristics of association of oleoyl derivatives of 5-fluorodeoxyuridine and
      methotrexate with low-density lipoproteins (LDL).
AB  - In order to prepare cytotoxic drug-low density lipoprotein (LDL) particles, we
      have synthesized lipophilic prodrugs of two broad-spectrum antineoplastic agents,
      methotrexate (MTX) and 5-fluorodeoxyuridine (FUdR), by coupling them to oleic
      acid. 3H-Labeled prodrugs were incorporated in 125I-LDL carriers, allowing the
      study of both drug and carrier simultaneously. Utilizing the dry film procedure,
      monooleoyl FUdR showed the highest incorporation efficiency with over 40% of the
      initial drug associated with LDL. The prepared prodrug-LDL solution was found to
      be a single complex of 30 molecules of prodrug per LDL particle when examined by
      agarose gel electrophoresis and density gradient ultracentrifugation. No unbound
      FUdROl1 could be recovered, indicating that all dissolved prodrug associates with
      LDL. After incubation of FUdROl1 with human serum, 22% of the compound associates
      with lipoproteins and 78% was recovered in the albumin-containing fraction. When
      human serum was pretreated with oleic acid in order to saturate albumin's fatty
      acids binding sites, a strong decrease (from 78 to 22%) in association to the
      albumin-containing fraction was observed, accompanied by a threefold increase
      (from 22 to 67%) in lipoprotein association. It is concluded that existing
      hydrophilic antineoplastic agents can be successfully modified in order to
      achieve association with LDL. This may ultimately lead to an increased delivery
      of cytotoxic drugs to tumor cells.

PMID- 1386670
TI  - Neocarzinostatin acts as a sensitive probe of DNA microheterogeneity: switching
      of chemistry from C-1' to C-4' by a G.T mismatch 5' to the site of DNA damage.
AB  - The diradical form of thiol-activated neocarzinostatin chromophore resides in the
      minor groove of DNA, where it has access to hydrogen atoms at the C-5', C-1', and
      C-4' positions of deoxyribose on each strand. In a dodecamer
      oligodeoxyribonucleotide containing the sequence AGC.GCT, a bistranded lesion
      staggered two nucleotides in the 3' direction, is generated that consists
      primarily of an abasic site (2'-deoxyribonolactone) at the C due to 1' chemistry
      and a direct strand break at the T due to 5' chemistry. Sequencing-gel analysis
      reveals that 72% of the damage at the C results from 1' chemistry with minor
      lesions consisting of a strand break due to 5' chemistry (15%) and 4' chemistry
      (less than 2%) and an abasic site (4'-hydroxylation product) (12%) due to 4'
      chemistry. Replacement of the G.C base pair 5' to the C by a G.T wobble mismatch
      results in a remarkable switching of the chemistry of damage at the C from C-1'
      to C-4'. The 1' chemistry is almost eliminated and replaced by 4' chemistry, so
      that the latter accounts for 64% of the damage, mainly in the form of the 4'
      hydroxylation product (abasic site) and a smaller amount of the DNA fragment with
      a phosphoglycolate at the 3' end (strand break). Substitution of the radiation
      sensitizer misonidazole for dioxygen markedly enhances partitioning of the 4'
      chemistry in favor of the glycolate-containing product. On the complementary
      strand the G.T mismatch results in an increase in 4' chemistry at the T residue,
      but 5' chemistry remains the main mechanism. When a G.A mismatch is inserted 5'
      to the C, there is a marked decrease in all damage at this site without
      detectable switching of chemistry. These results show that the diradical form of
      thiol-activated neocarzinostatin chromophore acts as sensitive probe of DNA
      microheterogeneity.

PMID- 1386671
TI  - Neurosteroids: pregnenolone in human sciatic nerves.
AB  - The characterization and quantification of pregnenolone in human sciatic nerves
      were undertaken, following previous demonstration of the synthesis of this
      steroid in rat brain oligodendrocytes, to explore the hypothesis that Schwann
      cells may demonstrate the same biosynthetic activity. Pregnenolone was
      definitively identified by mass spectrometry and quantified by specific
      radioimmunoassay. Its concentration (mean +/- SD, 63.9 +/- 45.9 ng/g of wet
      tissue, n = 12) was greater than or equal to 100 times the plasma level and
      concentration found in tendons and muscle. No correlation was found with sex or
      age. Free dehydroepiandrosterone as well as sulfate and fatty acid esters of
      pregnenolone and dehydroepiandrosterone were also measured. Results are discussed
      in terms of the concept that these "neurosteroids" may be synthesized in the
      peripheral nervous system.

PMID- 1386675
TI  - Defensive attribution hypothesis and serious occupational accidents.
AB  - Based on the defensive attribution hypothesis, we assume that the victims of
      serious occupational accidents tend to attribute their accidents to external
      factors, while their coworkers and foremen tend to attribute the accidents to the
      victims' own action. The data to test this hypothesis consisted of 99 serious
      occupational accidents in southern Finland. In connection with the accident, or
      after the investigation at the accident site, 73 victims, 65 coworkers, and 71
      foremen were interviewed. The results support our assumption, as the victims
      tended to use external attributions, whereas the foremen and coworkers attributed
      the accidents to internal factors. The defensive attribution hypothesis seems to
      explain the differences in how each party interpreted the basis for each
      accident.

PMID- 1386672
TI  - Carotid-aortic and renal baroreceptors mediate the atrial natriuretic peptide
      release induced by blood volume expansion.
AB  - Our previous studies have shown that stimulation of the anteroventral third
      ventricle (AV3V) region of the brain increases atrial natriuretic peptide (ANP)
      release, whereas lesions of the AV3V region or median eminence of the tuber
      cinereum block the release of ANP caused by blood volume expansion. These results
      suggest that participation of the central nervous system is critical to this
      response. The role of baroreceptors in the response was evaluated in the current
      research by studying the response of plasma ANP to blood volume expansion induced
      by intravenous injection of hypertonic saline solution (0.3 M NaCl, 2 ml/100 g of
      body weight, over 1 min) in conscious, freely moving male rats. Plasma samples
      were assayed for ANP by radioimmunoassay. In sham-operated rats, blood volume
      expansion induced a rapid increase in plasma ANP: the concentration peaked at 5
      min and remained elevated at 15 min after saline injection. One week after
      deafferentation of the carotid-aortic baroreceptors, basal plasma ANP
      concentrations were highly significantly decreased on comparison with values of
      sham-operated rats; plasma ANP levels 5 min after blood volume expansion in the
      deafferented rats were greatly reduced. Unilateral right vagotomy reduced resting
      levels of plasma ANP but not the response to blood volume expansion; resting
      concentrations of plasma ANP and responses to expansion were normal in
      bilaterally vagotomized rats. In rats that had undergone renal deafferentation,
      resting levels of ANP were normal but the response to blood volume expansion was
      significantly suppressed. The evidence indicates that afferent impulses via the
      right vagus nerve may be important under basal conditions, but they are not
      required for the ANP release induced by blood volume expansion. In contrast,
      baroreceptor impulses from the carotid-aortic sinus regions and the kidney are
      important pathways involved in the neuroendocrine control of ANP release. The
      evidence from these experiments and our previous stimulation and lesion studies
      indicates that the ANP release in response to volume expansion is mediated by
      afferent baroreceptor input to the AV3V region, which mediates the increased ANP
      release via activation of the hypothalamic ANP neuronal system.

PMID- 1386674
TI  - Partial loss of function mutations in DnaK, the Escherichia coli homologue of the
      70-kDa heat shock proteins, affect highly conserved amino acids implicated in ATP
      binding and hydrolysis.
AB  - A set of 37 mutations in DnaK, the Escherichia coli homologue of the 70-kDa heat
      shock proteins, was isolated using a selection for high constitutive expression
      of heat shock proteins. Of these, 11 mutants were able to carry out some but not
      all functions of DnaK. These partial function mutants were divided into two
      classes. Class I mutants are recessive and permit replication of bacteriophage
      lambda and growth of cells up to 40 degrees C. Class II mutants are dominant, do
      not permit growth of lambda, and are temperature-sensitive for growth above 34
      degrees C. Mutations in both classes alter amino acids that are highly conserved
      in the 70-kDa heat shock protein family. The dominant negative mutations provide
      strong genetic evidence that at least one form of DnaK is multimeric. Moreover,
      every dominant negative mutation occurs at an amino acid that has been
      hypothesized to be intimately involved in the process of ATP binding and
      hydrolysis. Our findings provide strong support for the hypothesis that such
      mutations are excellent tools for identifying amino acids that play critical
      roles in protein function.

PMID- 1386673
TI  - Human T-cell lymphotropic virus type I (HTLV-I) transcriptional activator, Tax,
      enhances CREB binding to HTLV-I 21-base-pair repeats by protein-protein
      interaction.
AB  - HTLV-I Tax protein activates transcription from three 21-base-pair (bp) repeat
      sequences in the viral enhancer. The HTLV-I 21-bp repeat contains a TGACGT motif
      that is homologous to the cAMP-responsive element (CRE) and crucial for tax
      transactivation. Tax exhibits marginal affinity for DNA but rather interacts with
      cellular CRE-binding proteins to enhance their affinity for the HTLV-I 21-bp
      repeats. Using the HTLV-I 21-bp repeat and Jurkat T-lymphocyte nuclear extract in
      a gel electrophoretic mobility-shift assay, we previously detected three protein
      DNA complexes that are specific for the CRE in the 21-bp repeat (complexes I, II,
      and IV). Complexes I and II but not IV interacted with Tax. We now show that
      complexes I, II, and IV are composed of CREB (CRE binding protein) homodimer,
      CREB/ATF-1 (activating transcription factor 1) heterodimer, and ATF-1 homodimer,
      respectively. Tax stabilizes complexes I and II via a direct interaction with the
      CREB moiety. In the absence of DNA, CREB and Tax continue to form a complex that
      can be immunoprecipitated by a Tax-specific antibody. These results suggest that
      one mechanism by which Tax activates transcription may be mediated through the
      direct interaction with CREB homodimer and/or CREB/ATF-1 heterodimer to stabilize
      their assembly on the Tax-responsive CRE motifs in the HTLV-I enhancer.

PMID- 1386676
TI  - [Effects of Iodine-131 in sheep depending on the content of stable iodine in the
      diet].
AB  - The biological effect of 131I was studied in sheep kept on a diet deficient in
      stable iodine. An increased capture and accretion of iodine in the thyroid gland
      and in the whole body were observed. The disturbances in the structure and
      function of the thyroid gland, liver and haemopoietic organs were more pronounced
      in the animals kept on the iodine deficient diet.

PMID- 1386677
TI  - Carbogen and nicotinamide: expectations too high? (response to J. Martin Brown)

PMID- 1386678
TI  - Extrapolations from laboratory and preclinical studies for the use of carbogen
      and nicotinamide in radiotherapy.

PMID- 1386679
TI  - Carbogen and nicotinamide: expectations too high?

PMID- 1386680
TI  - The caregiver reaction assessment (CRA) for caregivers to persons with chronic
      physical and mental impairments.
AB  - The development and testing of a multidimensional instrument to assess the
      reactions of family members caring for elderly persons with physical impairments,
      Alzheimer's disease, and cancer is reported. Forty items were administered to a
      sample of 377 caregivers of persons with physical impairments and Alzheimer's
      disease. Five dimensions of caregivers' reactions were identified through
      exploratory factor analysis. Using confirmatory factor analysis on an independent
      sample (N = 377), these dimensions were tested for factorial invariance across
      spouse and nonspouse caregivers and between caregivers of persons with cancer and
      those caring for persons with Alzheimer's disease. The subscales also had a high
      level of factorial invariance across a three-wave panel study (N = 185). The
      subscales appeared consistent with first order tests of construct validity.

PMID- 1386681
TI  - [Ergonomic and postural aspects in a central supply unit].
AB  - Unsuitable environmental factors can lead to back injuries. In order to develop a
      critical thinking about the workplace effects on human health, this paper discuss
      ergonomic and postural aspects in a Central Supply Unit.

PMID- 1386683
TI  - [Etiologic aspects of low back pain in rheumatic patients in Kinshasa (Zaire).
      Apropos of 169 cases].
AB  - A study over a period of 27 consecutive months showed that among patients seen in
      a Kinshasa hospital outpatient clinic for rheumatologic diseases, 46.5% sought
      medical advice for lower back pain. Lumbar arthrosis (74.5%), spondylodiscitis
      (9.5%) and unilateral sacroiliitis (9%) were the main causes of this complaint. A
      single patient had osteoporosis and no cases of ankylosing spondylarthritis were
      seen. Lumbar arthrosis was prevalent among females. Mean age of patients with
      disk disease was fairly low (43 years). Infectious spondylodiscitis and
      unilateral sacroiliitis, presumably reactive or infectious in origin, were also
      more common in women. HIV-infection was found in 44% of patients with
      spondylodiscitis and in 53% of patients with sacroiliitis. Age of HIV-infected
      individuals ranged from 21 to 40 years. Bacteriologic studies proved
      indispensable for determining the cause of these conditions in which leukocyte
      courts failed to rise. In young individuals in Kinshasa with spondylodiscitis or
      unilateral sacroiliitis, routine HIV testing is warranted.

PMID- 1386682
TI  - Patient and anatomical selectivity in postoperative radiotherapy for early breast
      cancer: a British perspective.
AB  - As radiotherapy following surgery for early breast cancer carries morbidity,
      financial cost, and potential mortality we have sought to select characteristics
      that will allow these risks to be minimised. The causes of increased mortality
      shown in the overview of mature trials of radiotherapy have been studied in a
      single large randomised trial. This has identified patients with large, poorly
      differentiated tumours to be most likely to benefit from the reduction in
      incidence of local recurrence achieved by radiotherapy while remaining at the
      lowest risk from suffering the increased mortality associated with the treatment.
      Much of the morbidity of radiotherapy is due to routine irradiation of lymphatic
      pathways. Three hundred and seven patients treated by breast-conserving surgery
      and breast radiotherapy have been evaluated. None received irradiation to their
      axilla or internal mammary lymphatics. Relapse in locoregional lymphatics (axilla
      or supraclavicular fossa) occurred in 15 patients. Only 4 had persisting symptoms
      from this relapse following further treatment.

PMID- 1386685
TI  - Taking a direct path to the genes.

PMID- 1386684
TI  - [Swiss Register for unrelated bone marrow donors: preliminary results].
AB  - Bone marrow transplantation from the unrelated volunteer donor is today a
      realistic possibility for patients lacking an HLA-identical family donor. In
      1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate
      such bone marrow transplants and create the Swiss volunteer donor registry. Thus
      for a search has been initiated for 71 patients and 16 transplants have been
      performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr
      identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of
      basic disease 2 weeks to 2 years and 4 months after the transplant. These results
      illustrate that unrelated donor transplantation, using careful selection
      criteria, is a realistic new therapeutic modality.

PMID- 1386686
TI  - Human cyclin B1 gene (CCNB1) assigned to chromosome 5 (q13-qter).
AB  - Cyclins play an important role in cell cycle regulation. At least five classes of
      cyclins have been identified--A, B, C, D, and E. B cyclins are generally of two
      types in most organisms--B1 and B2. We have mapped the gene for human cyclin B1
      (CCNB1) to human chromosome 5 (region q13-qter) by Southern blot analysis of
      human x Chinese hamster somatic cell hybrid panels. Many more cyclin B-related
      sequences have been identified in the mouse (Cycb-1 to Cycb-10) and have been
      mapped to chromosomes 4, 5, 7, 8, 13, 14, 15, and 17. Based on our mapping of
      human CCNB1 and known evolutionary conservation of chromosomal regions, we
      propose that the homologous cyclin B1 locus, Cycb-4, on mouse chromosome 13 is a
      functional gene.

PMID- 1386687
TI  - The less common occupational dermatoses.
AB  - Contact dermatitis and nonmelanoma skin cancer are the most common occupational
      skin disorders in North America, but there are many other occupational dermatoses
      that illustrate the wide range of pathological and adaptive responses of the skin
      to workplace exposure. Discussed are acne, chemically induced leukoderma, nail
      diseases, contact-related burns, high-pressure injection injuries, contact
      urticaria, heat reactions and photosensitivity, and infections.

PMID- 1386688
TI  - Factors that influence the outcome of aortoiliac and femoropopliteal percutaneous
      transluminal angioplasty.
AB  - In the past, patients with peripheral arterial occlusive disease were managed by
      conservative treatment or by vascular reconstructive surgery. Now, percutaneous
      transluminal angioplasty and other endovascular methods provide an important
      alternative for managing selected patients with peripheral arterial occlusive
      disease. Overall, the 5-year success rate after iliac angioplasty is 53.4%, but
      the success rate is higher if percutaneous transluminal angioplasty is performed
      on the common iliac artery or on a stenosed artery. In contrast, percutaneous
      transluminal angioplasty of the femoral and popliteal arteries has a relatively
      poor long-term success rate except for the treatment of patients with stenoses
      with good run-off. When the run-off is poor or an arterial occlusion is present,
      the role of femoropopliteal angioplasty is limited, and the procedure should be
      considered only for high-risk patients who do not have autogenous tissue for
      reconstructive surgery.

PMID- 1386689
TI  - Ultrasound recanalization of diseased arteries. From experimental studies to
      clinical application.
AB  - At present, percutaneous peripheral ultrasound angioplasty should be considered
      in those patients with symptoms of claudication or resting limb ischemia. With
      the development of an over-the-wire system, we treat patients with
      suprageniculate or infrageniculate lesions. It is expected that the over-the-wire
      probe will allow application of ultrasound angioplasty not only to lesions below
      the knee but to contralateral vascular occlusions as well. An intraoperative
      device for plaque ablation and arterial recanalization is in development for use
      in less accessible sites such as the coronary arteries. Experimental studies have
      shown that catheter-delivered therapeutic ultrasound recanalizes complete
      occlusions, reduces stenoses, dissolves thrombus, vasodilates, and enhances
      arterial distensibility. The potential clinical applications of therapeutic
      ultrasound include recanalizing total arterial occlusions, dissolving thrombi,
      facilitating balloon angioplasty by increasing arterial compliance, and as a
      stand-alone angioplasty device.

PMID- 1386690
TI  - Biology of restenosis and therapeutic approach.
AB  - Numerous attempts have been made to prevent restenosis after successful
      transluminal dilation of an atherosclerotic vessel using a variety of
      pharmacologic and mechanical approaches. This article reviews the pathobiology of
      the restenosis process, offers a hypothesis as to its cause, reviews attempts to
      modify the process, and outlines therapeutic approaches to future treatment.

PMID- 1386692
TI  - [Myocardial fibrosis of cattle in Hesse].
AB  - Between 1986 and 1989 there were 9 cases of idiopathic congestive heart failure
      at this clinic. Normally heifers in the last 1/3 of pregnancy and young cows aged
      between 2.5 and 3.5 years were affected, but the disease also occurred in one
      younger (1.5 years), one older (6 years) and in one male animal. In contrast to
      other reports, myocardial fibrosis in the State of Hesse was only seen in the
      Rotbunte breed. The animals suffered from a severe heart failure with venous
      congestion and congestive edema of the brisket, the submandibular area and the
      ventral abdomen. In most cases there is no precise difference in history,
      clinical findings and laboratory findings between myocardial fibrosis, traumatic
      pericarditis and endocarditis valvularis. Only pathological and histological
      examinations of the heart confirm a suspected myocardial fibrosis: The heart is
      enlarged and dilatated and seems to be non-elastic. Microscopically a scattered
      interstitial fibrosis and signs of myocardial degeneration are visible.

PMID- 1386693
TI  - Primed allogeneic reactions to leukocytes and epithelial cells in the bicolor
      damselfish.
AB  - The studies presented here describe allogeneic reactions in the bicolor
      damselfish, Pomacentrus partitus, a tropical marine teleost. Damselfish were
      immunized twice at 2-week intervals either by placement of reciprocal allografts
      or with primary cultures of epithelial cells. Two weeks after the second
      immunization, recipient splenocytes were tested for alloreactivity toward donor
      and third-party pronephros cells. For those animals immunized with cultured
      cells, reactivity toward donor and third-party epithelial cells was also
      examined. Unprimed animals responded to allogeneic pronephros between days 8 and
      10 (28 degrees C). Fish immunized with epithelial cells showed accelerated mixed
      leukocyte reactions, with optimal responses occurring between days 4 and 6.
      Moreover, responses to the immunogen preceded responses to donor pronephros
      tissue by 2 days, occurring on day 2 or day 4. In addition, primed responses were
      of significantly greater magnitude than primary reactions. Reactivity toward
      third-party pronephros tissue paralleled responses of naive animals, indicating
      the specificity of response. No reactivity toward epithelial cells was observed
      in the absence of immunization, suggesting that accessory cell functions of
      damselfish pronephros and epithelial cells differ.

PMID- 1386691
TI  - Effects of methacholine induced bronchoconstriction and procaterol induced
      bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric
      acid.
AB  - BACKGROUND: The direct effect of bronchoconstriction on cough receptor
      sensitivity is unknown, and the antitussive effect of beta 2 adrenergic agonists
      in man has been controversial. This study was designed to throw light on these
      questions. METHODS: The threshold of the cough response to inhaled capsaicin, a
      stimulant acting on C fibre endings, and tartaric acid, a chemostimulant, was
      measured before and 10 minutes after inhalation of methacholine, which caused a
      nearly 20% fall in forced expiratory volume in one second (FEV1), in 14 normal
      subjects (study 1), and also before and 30 minutes after inhalation of procaterol
      (30 micrograms), placebo, and saline in eight normal subjects (study 2).
      Progressively increasing concentrations of capsaicin and tartaric acid solutions
      were inhaled for 15 seconds by mouth tidal breathing at one minute intervals and
      cough threshold was defined as the lowest concentration of capsaicin and tartaric
      acid that elicited five or more coughs. RESULTS: In study 1 the geometric mean
      values of the cough threshold of response to capsaicin and tartaric acid before
      methacholine callenge, 2.98 (GSE 1.30) micrograms/ml and 46.6 (1.22) mg/ml, were
      not significantly different from those of the response to methacholine
      inhalation, 3.45 (1.33) micrograms/ml and 32.9 (1.37) mg/ml. In study 2 the
      geometric mean value of the cough threshold of response to capsaicin before
      inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml) was not different from
      that after inhalation of procaterol (4.61 (GSE 1.84) micrograms/ml), which had
      significant bronchodilator effects. The cough threshold was not altered by
      placebo or saline. CONCLUSIONS: These findings suggest that muscarinic receptor
      stimulation, bronchoconstriction, beta 2 receptor stimulation, or bronchodilation
      might have no direct effect on the sensitivity of the cough receptors in normal
      subjects.

PMID- 1386694
TI  - Selective loss of functional antidonor cytolytic T cell precursors following
      donor-specific blood transfusions in long-term renal allograft recipients.
AB  - Pretransplant administration of donor-specific blood transfusions prolongs the
      survival of HLA-disparate renal allografts to a level comparable to that of HLA
      identical transplants. To test the hypothesis that DST recipients develop
      immunologic tolerance of their donors, we examined antidonor T cell immunity in a
      group of DST recipients with long-term well-functioning allografts. Limiting
      dilution analysis studies indicated that 5/14 long-term DST recipients exhibit a
      complete absence of detectable antidonor cytolytic T lymphocyte precursors
      (CTLp). In contrast, 4/4 long-term non-DST recipients who received conventional
      or cyclosporine immunosuppression exhibited significant levels of antidonor CTLp.
      Nonresponsive DST recipients retained the capacity to mount antidonor responses
      in mixed lymphocyte reactions and IL-2 production assays, and exhibited normal
      levels of CTLp directed to third-party antigens. Addition of exogenous IL-2 to
      cell-mediated lympholysis cultures did not restore antidonor CTL responses. In
      summary, our data suggest that the DST conditioning regimen induces a complete
      yet selective loss of functional antidonor CTLp in some long-term renal
      transplant recipients.

PMID- 1386695
TI  - Positive correlation of T cell sensitization with frequencies of alloreactive T
      helper cells in chronic renal failure patients.
AB  - Chronic renal failure patients are often "sensitized" to foreign alloantigens
      following renal transplantation or blood transfusion. B cell sensitization is
      assessed by measuring the reactivity of cytotoxic antibodies in the patient's
      serum against a panel of allogeneic cells (panel-reactive antibodies, [PRA]).
      However, this technique provides no information about T cell allosensitization. T
      cell allosensitization may be important since T cells play a central role in
      allograft rejection and since "primed" alloreactive cells--i.e., T cells that
      have previously encountered their specific alloantigen, are relatively resistant
      to immunosuppression. In order to detect T cell sensitization we used a limiting
      dilution analysis assay, which measured both total and primed frequencies of
      alloreactive T helper (Th) cells. Total alloreactive Th cell frequencies were
      generally high. Primed alloreactive Th cell frequencies could be detected in all
      patients studied, although there was considerable variation in frequencies
      between different patients. Frequencies of primed Th cells did not correlate with
      levels of PRA. However, in all three of the patients who had received DR
      mismatched kidneys, and who had subsequently rejected these grafts rapidly, high
      primed frequencies were detected against the mismatched DR antigens. This was not
      the case for two patients who had lost their grafts two or more years after
      transplantation.

PMID- 1386696
TI  - Differences in patterns of allogeneic T-cell activation induced by melanoma
      macrophage hybrid cells.

PMID- 1386697
TI  - Immunosuppressive mechanism of action of deoxymethylspergualin--a human in vitro
      assay.

PMID- 1386698
TI  - Donor specific cell-mediated lympholysis (CML) by peripheral blood lymphocytes
      (PBL) from recipients with long-term renal grafts.

PMID- 1386699
TI  - Donor-specific blood transfusions (DST): clinical outcome and immunologic
      considerations.

PMID- 1386700
TI  - Plasma atrial natriuretic peptide, renin activity, and aldosterone in changes of
      body fluid volume after renal transplantation.

PMID- 1386701
TI  - The new cyclosporine derivative, SDZ IMM 125: in vitro and in vivo pharmacologic
      effects.

PMID- 1386702
TI  - Long-term safety profile of sandimmune in renal transplantation.

PMID- 1386703
TI  - Differences between the anticoccidial potencies of monensin in maize-based or
      wheat-based chicken diets.
AB  - Experiments were carried out to investigate why the anticoccidial ionophore
      monensin is more potent against the coccidium Eimeria tenella in chickens fed on
      a maize-based diet (as in the USA) than in chickens fed on a wheat-based diet (as
      in the UK). The explanation seems to be that the pathogenicity of E. tenella is
      lower in maize-fed chickens than in wheat-fed chickens, whether monensin is
      present in the diet or not. Possible reasons for this are suggested. The better
      survival of maize-fed birds may be partly due to protective effects of the higher
      concentrations of vitamins A and E derived from their diet. Furthermore, the
      higher concentrations of niacin and riboflavin in wheat than in maize may enhance
      coccidial pathogenicity. These opposing factors might combine to cause equivalent
      infection levels to produce more severe coccidiosis in chickens fed on a wheat
      based diet than on a maize-based diet.

PMID- 1386704
TI  - Identification of the major metabolites of [3H]-(+)-8-chloro-5-(2,3-
      dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrahydro- 1H-3-
      benzazepine in rats.
AB  - 1. The in vivo urinary metabolites of 3H(+)-8-chloro-5(2,3- dihydrobenzofuran-7
      yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrah ydro-1H-3- benzazepine isolated
      from Wistar rats have been characterized by mass spectrometry and n.m.r.
      spectroscopy. 2. Metabolites are formed by N-demethylation, hydroxylation of the
      dihydrobenzofuran moiety, and elimination of the methoxymethyl group followed by
      glucuronidation. All combinations of these metabolic pathways were found in the
      metabolites in urine. 3. In the faeces metabolites formed by hydroxylation of the
      dihydrobenzofuran moiety and elimination of the methoxymethyl moiety dominate,
      while N-demethylated metabolites are present only in small amounts. 4. The major
      plasma metabolite was formed by elimination of the methoxymethyl group followed
      by glucuronidation. Only minute amounts of other metabolites were present.

PMID- 1386705
TI  - [An epidemiological analysis of postoperative suppurative pathology in surgical
      hospitals].
AB  - Approaches to the epidemiological analysis of postoperative wound complications
      in surgical hospitals are summarized. The indices for the evaluation of the
      epidemic situation in surgical departments (the ratio of severe and mild forms of
      complications, severe and posthospital complications) are proposed. To determine
      the site of infection, the method of graphic analysis, involving the fixation of
      dates of the operation and the appearance of the complication and taking into
      account regularities in the development of the outbreak, the depth and severity
      of the lesion, is proposed. Epidemiological surveillance at medical institutions
      permits the prognostication of the epidemiological situation. The realization of
      epidemiological surveillance at the level of individual medical institutions is
      the prerequisite of effective functioning of the program of epidemiological
      surveillance at a given territory.

PMID- 1386706
TI  - [The comprehensive differentiated protection against influenza and acute
      respiratory diseases of medical workers in industrial enterprises].
AB  - Acute diseases of the respiratory organs rank first among temporary invalidity
      causes (30.5%). For the first time workers of a health center of an industrial
      enterprise were protected from influenza and ARVI during an epidemic outbreak of
      influenza A by specific and nonspecific protection means with due consideration
      for the subject's health status and will. Comprehensive differentiated protection
      from influenza and ARVI proved highly effective, its index reaching 2.5 and the
      invalidity periods being shorter by 2.4-4 days.

PMID- 1386707
TI  - [The characteristics of a Russian-made kit for the serological identification of
      streptococci groups A, B and C].
AB  - The first Soviet kits for the serological identification of streptococci, groups
      A, B, and C, on the basis of the coagglutination test were developed. Each kit
      was intended for 35-40 determinations. The optimum concentration of streptococci
      during their identification by means of the reagents making up the kit was about
      1.6 x 10(9) cells/ml. The specificity of the reagents in comparison with the
      results of the identification of streptococci by reference methods was 97.3 +/-
      0.9%. The reagents making up the kits can be presumably used for solving a number
      of practical problems in the epidemiological surveillance of streptococcal
      infection.

PMID- 1386709
TI  - Reversal of neurologic deficits in Down syndrome.

PMID- 1386708
TI  - Multiple insulin-responsive elements regulate transcription of the GAPDH gene.
AB  - Multiple elements in the upstream region of the GAPDH gene play a role in
      mediating the acute and chronic effect of insulin on GAPDH gene expression. The
      complexity of this regulation provides many layers of control. In differentiated
      tissues, the transcriptional response to insulin results from the additive
      effects of g/TRE, IRE-A and IRE-B. The gTRE may interact with newly synthesized c
      fos/c-jun heterodimer to activate GAPDH gene transcription. Studies are underway
      to determine whether protein synthesis inhibitors affect the regulation of GAPDH.
      Because there are several elements that mediate the effect, it will be difficult
      to determine the significance of these findings until each cis-acting factor and
      its binding protein can be studied in isolation. IRE-A and IRE-B act together to
      promote a 5- to 8-fold insulin effect on HGAPDH-CAT in H35 hepatoma cells and a 3
      fold effect in 3T3 adipocytes. We have succeeded in detecting an insulin
      sensitive DNA-binding protein referred to as IREA-BP with an element -480 to 
      435. Insulin treatment of differentiated 3T3 adipocytes for 1 hr results in a 4
      fold increase in the amount of this binding protein, as estimated by the amount
      of 32P-labelled oligonucleotide retarded on non-denaturing PAGE (11). The effect
      of insulin on IRP-B is comparable. Furthermore, IREA-BP is induced during the
      process of fasting and refeeding rats, an important in vivo correlate with our
      tissue culture models (11). These observations imply that the binding proteins
      IREA-BP and IRP-B are essential components in the signal transduction pathway of
      insulin action on GAPDH gene expression in metabolically active tissues such as
      fat and liver. Differentiation-dependence and tissue-specificity are achieved
      through multiple regulatory elements and involve pre- and post-translational
      regulation of multiple transcription factors. IREA-BP is present in preadipocytes
      but activity in highly induced upon differentiation of preadipocytes to
      adipocytes. The IRE-B (-408 to -269) DNA binding protein is not detected in 3T3
      preadipocytes. A gC/EBP like-protein takes part in the formation of this complex
      which may explain the inductive effect of differentiation on binding. Finally,
      footprint and cotransfection studies indicate that the differentiation-dependent
      protein C/EBP also regulates GAPDH gene transcription through a motif located
      within one hundred nucleotides of the promoter. We have begun to clone the IRE-A
      and IRE-B DNA binding proteins. An IRE-A binding protein that footprints the 3'
      domain of the IRE-A has been cloned.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1386710
TI  - Comparative study of microsatellite and cytogenetic markers for detecting the
      origin of the nondisjoined chromosome 21 in Down syndrome.
AB  - Nondisjunction in trisomy 21 has traditionally been studied by cytogenetic
      heteromorphisms. Those studies assumed no crossing-over on the short arm of
      chromosome 21. Recently, increased accuracy of detection of the origin of
      nondisjunction has been demonstrated by DNA polymorphism analysis. We describe a
      comparative study of cytogenetic heteromorphisms and seven PCR-based DNA
      polymorphisms for detecting the origin of the additional chromosome 21 in 68
      cases of Down syndrome. The polymorphisms studied were the highly informative
      microsatellites at loci D21S215, D21S120, D21S192, IFNAR, D21S156, HMG14, and
      D21S171. The meiotic stage of nondisjunction was assigned on the basis of the
      pericentromeric markers D21S215, D21S120, and D21S192. Only unequivocal
      cytogenetic results were compared with the results of the DNA analysis. The
      parental and meiotic division origin could be determined in 51% of the cases by
      using the cytogenetic markers and in 88% of the cases by using the DNA markers.
      Although there were no discrepancies between the two scoring systems regarding
      parental origin, there were eight discrepancies regarding meiotic stage of
      nondisjunction. Our results raise the possibility of recombination between the
      two marker systems, particularly on the short arm.

PMID- 1386712
TI  - The use of carbon dioxide laser laparoscopy in the treatment of tubal ectopic
      pregnancies.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of the treatment
      of unruptured tubal ectopic pregnancies by the use of carbon dioxide laser
      laparoscopy. STUDY DESIGN: A series of 125 consecutive ectopic pregnancies were
      treated laparoscopically; the tubal pregnancy was removed by a laparoscopic laser
      technique. Preoperative assessment included monitoring beta-human chorionic
      gonadotropin levels, use of vaginal ultrasonography, and preoperative and
      postoperative hematocrit levels. RESULTS: Laparoscopic laser surgery was
      successful for removal of tubal ectopic pregnancies in all but four patients, in
      whom a laparotomy was required. Hematocrit levels before and after surgery were
      similar. The time necessary for beta-human chorionic gonadotropin to fall to
      nondetectable levels averaged between 3 and 4 weeks. There were five patients who
      had complications requiring additional surgery and/or medical treatment.
      CONCLUSION: The techniques are easy to learn, and the use of laparoscopic laser
      surgery in the treatment of tubal ectopic pregnancies appears to be a safe
      procedure with definite advantages for both the patient and the physician. There
      are decreased operating times, shorter hospital stays, and lower medical costs
      compared with those for major surgery. Subsequent successful intrauterine
      pregnancy rates are comparable to those of conservative methods previously
      reported.

PMID- 1386711
TI  - Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome
      7q35.
AB  - The chromosomal localization of the gene for Thomsen disease, an autosomal
      dominant form of myotonia congenita, is unknown. Electrophysiologic data in
      Thomsen disease point to defects in muscle-membrane ion-channel function. A mouse
      model of myotonia congenita appears to result from transposon inactivation of a
      muscle chloride-channel gene which maps to a region of mouse chromosome 6. The
      linkage group containing this gene includes several loci which have human
      homologues on human chromosome 7q31-35 (synteny), and this is a candidate region
      for the Thomsen disease locus. Linkage analysis of Thomsen disease to the T-cell
      receptor beta (TCRB) locus at 7q35 was carried out in four pedigrees (25 affected
      and 23 unaffected individuals) by using a PCR-based dinucleotide repeat
      polymorphism in the TCRB gene. Two-point linkage analysis between Thomsen disease
      and TCRB showed a maximum cumulative lod score of 3.963 at a recombination
      fraction of .10 (1-lod support interval .048-.275). We conclude that the Thomsen
      disease locus is linked to the TCRB locus in these families.

PMID- 1386713
TI  - Interferon-gamma receptors on human gestational choriocarcinoma cell lines:
      quantitative and functional studies.
AB  - OBJECTIVES: This study was performed to further define the effects of interferon
      gamma on choriocarcinoma cell lines and to determine whether variations in
      response among cell lines are attributable to quantitative differences in
      interferon-gamma receptors. STUDY DESIGN: Interferon-gamma receptors were
      quantified on BeWo, JEG-3 and Jar choriocarcinoma cell lines by a radiolabeled
      interferon-gamma ligand binding assay. The response of these cell lines to
      interferon-gamma was measured in two functional assays: a cell proliferation
      assay and a cell lysis assay after exposure to interferon-gamma with and without
      actinomycin-D. RESULTS: The number of interferon-gamma receptors on BeWo, Jar,
      and JEG-3 cells did not differ significantly (650, 560, and 420 interferon-gamma
      receptors per cell, respectively). Proliferation of all three choriocarcinoma
      cell lines was significantly inhibited to a similar extent by interferon-gamma.
      After treatment with interferon-gamma actinomycin-D, each choriocarcinoma cell
      line exhibited dose-dependent cell lysis; lysis of Jar was significantly less
      than that of either BeWo or JEG-3. CONCLUSION: These data further document
      variations in the response of choriocarcinoma cell lines to interferon-gamma and
      indicate that these differences are not the result of interferon-gamma receptor
      number but of postreceptor mechanisms.

PMID- 1386714
TI  - Alzheimer's disease. Beta-amyloid precursor protein expression in the nucleus
      basalis of Meynert.
AB  - The nucleus basalis of Meynert (nbM) was examined using immunocytochemistry for
      beta-amyloid precursor protein (beta APP) expression in Alzheimer's disease (AD).
      In mild AD cases, light labeling of the cell body and proximal processes was
      observed, and small intracellular structures were labeled rarely. In the more
      severe cases, intense cytoplasmic beta APP labeling was seen, often along with
      small beta APP-positive structures. Double-labeling experiments demonstrated that
      in the more severe cases these small structures were also decorated by a
      neurofibrillary tangle (NFT) antiserum. Other neurons in the severe cases showed
      incorporation of beta APP into large inclusions, which were also labeled with the
      NFT antiserum. However, some large inclusions in the severe cases were labeled by
      the NFT antiserum but contained no beta APP. Extraneuronal NFTs did not show beta
      APP labeling and did not react with an antibody to the beta-amyloid peptide.
      These results suggest that increased expression of beta APP coincides with
      intracellular NFT formation in the nbM, but that the formation of extraneuronal
      NFTs results in a loss of beta APP immunoreactivity.

PMID- 1386716
TI  - Effects of copper deficiency on T-cell mitogenic responsiveness and phenotypic
      profile of blood mononuclear cells from swine.
AB  - The effect of dietary copper deficiency on T-cell mitogenic responsiveness and
      phenotypic profile of blood mononuclear cells (MNC) in weaned pigs was examined.
      Outbred, weaned pigs were fed a semipurified diet containing adequate (6.4 mg/kg
      of body weight) or deficient (0.8 mg/kg) amounts of Cu. Pigs fed the low Cu diet
      for 10 weeks had markedly decreased concentrations of Cu in liver and plasma, and
      hypertrophic hearts. In vitro reactivity of MNC from Cu-deficient pigs to
      phytohemagglutinin and concanavalin A was significantly suppressed. This
      functional impairment was not associated with a decrease in the percentage of T
      cells, CD4 or CD8 cell subsets, or B cells. Expression of SLA-DQ and SLA-DR class
      II major histocompatibility complex (MHC) antigens was increased by Cu
      deficiency, the former significantly. Unlike rodents, in which inadequate Cu
      nutriture induces functional T cell deficiency that is associated with a decrease
      in the CD4 T-cell subset, swine fed inadequate Cu diets for 10 weeks had no
      changes in MNC subsets yet clearly manifested functional impairment of T-cell
      responses.

PMID- 1386717
TI  - [Allergic drug reactions in children].
AB  - We present a retrospective study of allergic drug reactions seen in our pediatric
      allergy consulting room during the last 6 years. During this time, 840 patients
      were examined for suspected adverse drug reactions. Drug allergy was confirmed in
      72 cases (8.5%). Of these cases, 29 (40.2%) were considered to be IgE mediated,
      or immediate hypersensitivity reactions. We have not found significant
      differences with regards to age, sex, atopic family history or atopia between
      patients with IgE mediated reactions compared to patients with allergic drug
      reactions of different mechanisms or to patients without drug allergies.
      Sulfonamides, streptomycin, beta-lactam and analgesics were the drugs most
      frequently involved in immediate type reactions. Among non-immediate reactions,
      fixed eruption by sulfonamides and contact dermatitis due to Mercurochrome were
      the most frequent.

PMID- 1386718
TI  - Free thin paraumbilical perforator-based flaps.
AB  - A free paraumbilical perforator-based flap fed by a muscle perforator from the
      inferior deep epigastric artery and with no muscle was used in 13 patients. Among
      them, a free thin paraumbilical perforator-based flap with a thin layer of fat,
      to protect the subdermal plexus of the vessels, was used in seven patients. The
      dominant pedicle perforator of this thin flap is usually located around the
      umbilicus and a large flap can be obtained. Its critical length-to-breath ratio
      is considered to be 4:3. The advantages of this flap are a long and large
      vascular pedicle, rare postoperative abdominal herniation, little bulkiness of
      the flap, and a relatively large skin territory. The disadvantages are technical
      difficulties in dissection of the perforator and anatomical variation in the
      location of the perforator. We believe this flap largely overcomes the problems
      of the conventional rectus abdominis musculocutaneous flap.

PMID- 1386715
TI  - Expression of developmentally defined retinal phenotypes in the histogenesis of
      retinoblastoma.
AB  - Retinoblastoma, the most common intraocular tumor of childhood, is a malignant
      neoplasm that arises during retinal development. The embryonal cell target for
      neoplastic transformation is not yet clearly defined. To better understand the
      histogenetic potential of this tumor, the expression of photoreceptor and glial
      cell-associated proteins were examined in 22 primary retinoblastomas.
      Interphotoreceptor retinol-binding protein (IRBP), cone and rod opsins were
      selected as the photoreceptor specific proteins due to their different temporal
      patterns of expression during normal retinal development. Neoplastic Muller cell
      differentiation, and non-neoplastic reactive astrocytes were identified using
      cellular retinaldehyde binding-protein (CRAlBP), and glial fibrillary acidic
      protein (GFAP), respectively. Photoreceptor proteins were present in 16 cases and
      showed different cellular patterns of expression. IRBP and cone opsin were
      usually abundant. Although rod opsin was clearly identified in eight tumors, its
      expression was more restricted than either IRBP or cone opsin. This differential
      pattern of expression, opposite to the normal pattern of photoreceptor gene
      expression in the adult retina, corresponded to a marked decrease in mRNA for rod
      opsin. Cone opsin and IRBP colocalized in fleurettes demonstrating that
      neoplastic human cone cells are capable of IRBP synthesis. Muller cell
      differentiation was present in 12 of the 16 cases in which photoreceptor proteins
      were detected. In contrast, GFAP was only present in reactive, stromal astrocytes
      associated with blood vessels. Our data suggest that the retinoblastoma has the
      histogenetic potential of the immature neural retinal epithelium which can give
      rise to both photoreceptor and Muller cell lineages. The differential expression
      of cone and rod phenotypes in retinoblastoma is consistent with the "default"
      mechanism of cone cell differentiation.

PMID- 1386719
TI  - Abdominoplasty combined with other intraabdominal procedures.
AB  - One hundred three patients underwent abdominoplasty combined with other
      intraabdominal procedures including 67 tubal ligations, 34 total abdominal
      hysterectomies and 2 cholecystectomies, from January 1983 to July 1991. The
      patients were divided into two groups, those undergoing the standard or total
      abdominoplasty and those undergoing limited abdominoplasty with or without
      liposuction in delimited areas. In this series of 103 patients, we found only two
      minor complications and only three patients were transfused with autologous units
      of blood. When performed by well-schooled surgical teams, abdominoplasty may be
      combined with intraabdominal procedures with gratifying results.

PMID- 1386721
TI  - Characterization and partial purification of an insulinase from Neurospora
      crassa.
AB  - An insulin-binding metal- and thiol-dependent proteinase has been purified 1491
      fold from high speed cytosolic fractions of the fungus Neurospora crassa. This
      enzyme resembles insulin-degrading enzymes (insulinases) present in mammalian
      cells and in Drosophila melanogaster in the following ways: (i) it degrades
      radiolabeled insulin with a specificity similar to that of rat muscle insulinase,
      as demonstrated by HPLC analysis of the degradation products; (ii) it is
      inhibited by bacitracin, EDTA, 1,10-phenanthroline, and the sulfhydryl-reactive
      compounds N-ethylmaleimide and p-chloromercuribenzoate, but not by inhibitors of
      serine proteases or by lysosomal protease inhibitors. Cross-linking with 125I
      insulin labels a band of ca. 120 kDa, and several smaller bands which may
      represent degradation products. The N. crassa insulinase is stimulated by Mn2+
      and strongly inhibited by Zn2+; Mn2+ can also reactivate the enzyme after
      inhibition by EDTA, but Zn2+ is ineffective. The N. crassa protein differs in
      this regard from mammalian and insect insulinases which are generally activated
      by both Mn2+ and Zn2+. This finding extends the apparent evolutionary
      conservation of these metal- and thiol-dependent proteases into the microbial
      realm.

PMID- 1386720
TI  - Alterations in the cell wall of Saccharomyces cerevisiae induced by the alpha sex
      factor or a mutation in the cell cycle.
AB  - We performed experiments in parallel to study the rate of synthesis of cell wall
      polysaccharides and the activity of glycosyl transferases in Saccharomyces
      cerevisiae after arrest of a cdc 28 mutant in G1 phase by either addition of
      alpha-factor or transfer to the non-permissive temperature. Both effectors
      brought about similar time-dependent increases in the rate of synthesis and
      deposition of the cell wall polysaccharides chitin, glucan and mannan. These
      changes in cell wall composition were accompanied by an increase in the specific
      activities of glucan and chitin synthetases. This increase was inhibited by
      cycloheximide suggesting that it represented de novo enzyme biosynthesis and not
      enzyme activation. Our data are consistent with the notion that both alpha-factor
      and the cdc 28 mutation affect the same stage-specific function that controls the
      temporal expression of glycosyl transferases.

PMID- 1386722
TI  - F1-ATPase with cysteine instead of serine at residue 373 of the alpha subunit.
AB  - Escherichia coli strain AN718 contains the alpha S373F mutation in F1F0-ATP
      synthase which blocks ATP synthesis (oxidative phosphorylation) and steady-state
      F1-ATPase activity. The revertant strain AN718SS2 containing the mutation alpha
      C373 was isolated and shown to confer a phenotype of higher growth yield than
      that of the wild type in liquid medium containing limiting glucose, succinate, or
      LB. Purified F1 from strain AN718SS2 was found to have 30% of wild-type steady
      state ATPase activity and 60% of wild-type oxidative phosphorylation activity.
      Azide sensitivity of ATPase activity and ADP-induced enhancement of bound
      aurovertin fluorescence, both of which are lost in alpha S373F mutant F1, were
      regained in alpha C373 F1. N-Ethylmaleimide (NEM) inactivated alpha C373 F1
      steady-state ATPase potently but had no effect on unisite ATPase. Complete
      inactivation of alpha C373 F1 steady-state ATPase corresponded to incorporation
      of one NEM per F1 (mol/mol), in just one of the three alpha subunits. NEM
      inactivated enzyme showed azide-insensitive residual ATPase activity and loss of
      ADP-induced enhancement of bound aurovertin fluorescence. The data confirm the
      view that placement at residue alpha 373 of a bulky amino acid side-chain
      (phenylalanyl or NEM-derivatized cysteinyl) blocks positive catalytic
      cooperativity in F1. The fact that NEM inhibits steady-state ATPase when only one
      alpha subunit of three is reacted suggests a cyclical catalytic mechanism.

PMID- 1386723
TI  - Catalytic properties of Escherichia coli F1-ATPase depleted of endogenous
      nucleotides.
AB  - Nucleotide-depleted Escherichia coli F1 was prepared by the procedure of Wise et
      al. (1983, Biochem. J. 215, 343-350). This enzyme had high rates of steady-state
      ATPase and GTPase activity. When "unisite" ATP hydrolysis was measured using an
      F1/ATP concentration ratio of 10, all of the substoichiometric ATP became bound
      to the high-affinity catalytic site and none became bound to noncatalytic sites.
      The association rate constant for ATP binding was 7 x 10(5) M-1 s-1 and the KdATP
      was 7.9 x 10(-10) M, as compared to values of 3.8 x 10(5) M-1 s-1 and 1.9 x 10(
      10) M, respectively, in native (i.e., nucleotide-replete) F1. Rate constants for
      bound ATP hydrolysis, ATP resynthesis, and P(i) release, and the reaction
      equilibrium constant, were similar in nucleotide-depleted and native F1.
      Therefore, we conclude that occupancy of the noncatalytic sites is not required
      for formation of the high-affinity catalytic site of F1 and has no significant
      effect on unisite catalysis. In further experiments we looked for the occurrence
      of inhibitory, catalytic-site-bound MgADP in E. coli F1. Such an entity has been
      reported for chloroplast and mitochondrial F1. However, our experiments gave no
      indication for inhibitory MgADP in E. coli F1.

PMID- 1386724
TI  - Inhibition of glucocerebrosidase and induction of neural abnormality by
      cyclophellitol in mice.
AB  - Cyclophellitol, a cyclitol with an epoxide, is a novel microbial secondary
      metabolite that inhibits beta-glucosidase and beta-glucocerebrosidase. Daily
      administration of cyclophellitol induces a severe abnormality of the nervous
      system in mice while it has no toxicity in various cultured cells. It was shown
      to inhibit glucocerebrosidase in vivo significantly in mice and the content of
      glucocerebroside in liver, spleen, and brain was increased markedly. The enzyme
      activity was completely suppressed in brain, liver, spleen, kidney, and muscle.
      On the other hand hexosaminidase activity was not affected in all tissues. After
      a single administration of cyclophellitol the maximal inhibition of
      glucocerebrosidase was observed within 30 min in brain and liver, and the
      inhibition lasted for 2-4 days. A single administration of cyclophellitol also
      induced a severe abnormality of the nervous system known as Gaucher's-like
      disease in mice. Conduritol B epoxide is also known to inhibit glucocerebrosidase
      and induce Gaucher's like-disease in mice by repetitive injection. Cyclophellitol
      was shown to be more potent than conduritol B epoxide in inhibition of
      glucocerebrosidase and in induction of the neural abnormality.

PMID- 1386725
TI  - Fasting serum insulin levels in essential hypertension. A meta-analysis.
AB  - BACKGROUND--The role of insulin in the genesis of essential hypertension remains
      an area of intense controversy. Most clinical evidence suggests a definite
      association. Several pathophysiologic mechanisms have been proposed. However,
      current data remain disparate and contradictory. METHODS--Meta-analysis allows
      data pooling of primary study findings and subsequent integration into a
      statistically meaningful outcome. This method was used to study the relationship
      in euglycemic individuals between blood pressure and fasting serum insulin level,
      age, body mass index, and fasting plasma glucose level. RESULTS: -A significant
      correlation was demonstrated between fasting serum insulin concentration and both
      systolic blood pressure and diastolic blood pressure. Age and body mass index
      also revealed meaningful associations. The meta-analytic correlation between
      plasma glucose level and both systolic blood pressure and diastolic blood
      pressure failed to achieve significance. CONCLUSIONS--Data from a meta-analytic
      review examining fasting serum insulin levels in euglycemic individuals
      demonstrate a significant correlation with systolic and diastolic blood pressure.
      This study supports the role of hyperinsulinemia in the pathogenesis of essential
      hypertension.

PMID- 1386726
TI  - Five-minute treatments with fluorouracil, floxuridine, and mitomycin have long
      term effects on human Tenon's capsule fibroblasts.
AB  - Proliferating human Tenon's capsule fibroblasts were exposed for 5 minutes to a
      wide range of concentrations of fluorouracil, floxuridine, and mitomycin. High
      concentrations of all three agents had prolonged effects on cell proliferation
      and morphologic characteristics compared with untreated control cells up to 36
      days. The highest concentrations of both floxuridine (15,000 micrograms/mL) and
      mitomycin (1000 micrograms/mL) had an apparent cidal effect, reducing cell
      numbers below initial cell density. In contrast, although the highest
      concentration of fluorouracil (25,000 micrograms/mL) inhibited cell proliferation
      by more than 50% relative to the untreated control cells at 36 days, the cell
      numbers still increased fourfold compared with the initial cell density. These
      results demonstrate that 5-minute treatments with high concentrations of these
      drugs have prolonged effects on the proliferation of human Tenon's capsule
      fibroblasts in vitro. Single-dose regimens using high concentrations of these
      drugs at the time of operation may achieve results similar to those of protocols
      that involve repeated applications.

PMID- 1386727
TI  - Lipoprotein(a) levels in chronic renal disease states, dialysis and
      transplantation.
AB  - Lipoprotein(a) is an independent risk factor for cardiovascular disease.
      Lipoprotein(a) levels were measured in 196 patients (103 Male [M]: 93 Female [F])
      with chronic renal diseases and in 116 controls. Median levels of Lipoprotein(a)
      [Lp(a)] were found to be significantly elevated in patients with untreated
      chronic renal disease (285,285 mg/L; M,F; range 30-1675 mg/L) and in those
      treated with continuous ambulatory peritoneal dialysis (320, 603; M,F; range 50
      1450) compared with controls (70,51; M,F; range 1-750; p less than 0.01 Males, p
      less than 0.001 Females). Lp(a) levels in patients treated by haemodialysis
      (133,35; M,F; range 5-685) and renal transplantation (100,95; M,F; range 10-1700)
      were not significantly different from controls. Lipoprotein(a) levels correlated
      inversely with serum albumin in the combined dialysis group (r = -0.34, p less
      than 0.001), and with urinary protein loss in the combined transplant and chronic
      renal diseases groups (r = 0.29, p less than 0.01). This correlation of Lp(a)
      with protein metabolism suggests a similarity with changes in other
      apolipoprotein-B containing lipoproteins in nephrosis. These findings may be
      relevant to the increased risk of atherosclerosis in patients with chronic renal
      disease and to their optimum mode of renal replacement therapy.

PMID- 1386728
TI  - Trabecular spacing in post-menopausal Australian women with and without vertebral
      fractures.
AB  - Histomorphometric measurements were made from iliac crest biopsies of 32 women
      with vertebral fractures and 37 women without fracture. All were post-menopausal
      Australian women who had presented with back pain to a hospital out-patient
      endocrinology clinic. Bone from the fracture cases was characterised by loss of
      individual trabecular elements, with the remaining trabeculae being spaced
      further apart than those in the non-fracture women (p less than 0.0001). This
      resulted in a significant decrease in trabecular bone volume (p less than 0.01).
      In addition osteoid surface was reduced (p less than 0.01). Dynamic parameters of
      bone turnover were not significantly different between the two groups. These data
      should be useful for the assessment of iliac bone histomorphometry in Australian
      post-menopausal women suspected of having osteoporosis.

PMID- 1386729
TI  - Troponin T isoform expression in the normal and failing human left ventricle: a
      correlation with myofibrillar ATPase activity.
AB  - The expression of troponin T, a thin filament regulatory protein, was examined in
      normal and failing left ventricles. The samples were obtained from the hearts of
      patients with severe heart failure who were undergoing cardiac transplantation,
      and from normal adult hearts that could not be used for transplantation. Western
      blots of the myofibrillar proteins demonstrated two isoforms, troponin T 1 (TnT1)
      and troponin T 2 (TnT2). TnT2 is expressed at significantly higher levels in
      failing hearts (p less than 0.004). Western blots of two-dimension SDS-PAGE gels
      resolved two dominant spots of TnT1 and of TnT2 and several minor troponin T
      species. Alkaline phosphatase treatment markedly decreased the sizes of the two
      acidic spots while increasing the two more basic spots by a comparable amount.
      Myofibrillar ATPase activity had an inverse and negative linear relationship (r =
      0.7, p less than 0.02) with the myofibrillar percentage of total troponin T
      comprised of TnT2. In that heart failure in these transplant patients had
      multiple bases, we propose that rather than a cause of heart failure, the disease
      associated changes in troponin T isoform expression are an adaptation to abnormal
      myocardial function.

PMID- 1386730
TI  - Effects of different expression and posttranslational modifications of myosin
      light chains on contractility of skinned human cardiac fibers.
AB  - In the human ventricle two isoforms of the phosphorylatable myosin light chain
      (MPLC) are expressed. These two forms are designated with increasing acidity as
      LC-2 and LC-2*. In the normal human heart the relation between LC-2/LC-2*
      expression is 70/30, suggesting the existence of three different myosin
      isoenzymes (MPLC-polymorphism) in the normal human ventricle. Both ventricular
      MPLC-isoforms are monophosphorylated, the LC-2 being higher phosphorylated than
      the LC-2*. In some patients with heart failure both MPLC isoforms were found to
      be completely dephosphorylated. In the human atrium a MPLC isoform is expressed
      which is different from the ventricular MPLC isoforms. The atrial MPLC isoform is
      mono- and diphosphorylated. Mono-phosphorylation of both the ventricular MPLC
      isoforms and the atrial MPLC isoform increased responsiveness as well as
      sensitivity of isometric tension generation of skinned fibers to Ca2+. Part of
      this effect could be explained by changing the cross-bridge-cycling rate: MPLC
      increased fapp, the rate-constant for the transition of cross-bridges from the
      non-force into the force-generating state, thus increasing the amount of force
      generating cross-bridge states at a given [Ca2+]. Monophosphorylation of the MPLC
      isoforms did not change maximal shortening velocity.

PMID- 1386731
TI  - Contractile proteins and sarcoplasmic reticulum calcium-ATPase gene expression in
      the hypertrophied and failing heart.
AB  - The physiology of myocardial contractility has been studied for over a century,
      but only recently has molecular biology provided new insights into the mechanisms
      responsible for the alterations of contraction and relaxation observed during
      cardiac hypertrophy and heart failure. Pressure and volume overload produce in
      the myocyte both qualitative changes characterized by protein isoform switches
      and quantitative changes characterized by modulation of single genes through a
      mechanogenic transduction the pathways of which are largely unknown. The
      qualitative changes involve differential expression of multigene families of
      contractile proteins, especially myosin heavy chain (MHC) and actin. All
      situations of pressure overload, or of combined pressure and volume overload
      activate the beta-MHC gene and deactivate the alpha-MHC one, which leads to a
      slower, more efficient contraction. In rat, pressure overload transitorily
      activates the alpha-skeletal actin gene, and both the timing and the distribution
      of the newly formed beta-MHC and alpha-skeletal actin mRNAs differ. We recently
      found that the isoactin pattern is the same in patients with end-stage heart
      failure as that of control human hearts. Moreover, both in rat and human,
      expression of isomyosins and isoactins are not coordinated, neither during
      ontogeny nor senescence. All this suggests the existence of several regulatory
      mechanisms activated during normal cardiac growth or by a mechanical trigger, and
      preliminary results indicate that it is possible to perform nuclear run-on assays
      in order to analyze the transcriptional step of these isogenes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1386732
TI  - Structural and functional diversity of human ventricular myosin.
AB  - The role of subcellular alterations in the process of heart failure remains ill
      defined. Because contractile performance of failing heart muscle is depressed,
      possible alterations in the myosin molecule could be of particular relevance.
      There is increasing evidence that myofibrillar ATPase activity is reduced in
      congestive heart failure, whereas the findings on myosin ATPase are still
      controversial. The molecular causes of the reduced activity are currently not
      known. Because alpha-MHC is present only in small amounts in normal ventricles, a
      shift in favor of beta-MHC is of minor importance. Also immunohistochemical data
      on subspecies of beta-MHC seem not to provide an explanation. A new type of
      myosin heterogeneity was found by optimizing native polyacrylamide gel
      electrophoresis in the presence of pyrophosphate. Two bands (VA and VB) were
      observed in ventricles of patients with valvular disease. Because the two bands
      were detected also in normal hearts of large mammals, the existence of VA/VB
      cannot be diagnostic of diseased heart. However, the VA/VB ratio was influenced
      by the hemodynamic load, whereby the fast migrating band (VA) increased with the
      diastolic and systolic load. Because a relationship with the hemodynamic load was
      observed only in surgical muscle specimens, it appears that this heterogeneity is
      prone to post mortem modification. Further work is required to identify the
      molecular nature of this heterogeneity and to examine the therapeutic potential
      of a pharmacological modification of the VA/VB ratio.

PMID- 1386733
TI  - Inhibition of tonoplast ATPase from etiolated mung bean seedlings by fluorescein
      5'-isothiocyanate.
AB  - Fluorescein 5'-isothiocyanate (FITC) was used to modify the lysine residue in the
      active site of tonoplast H(+)-ATPase from etiolated mung-bean (Vigna radiata L.)
      seedlings. FITC caused marked inactivation of the enzyme activities of both
      membrane-bound and soluble ATPase and its associated H+ translocation. The
      SDS/PAGE pattern revealed that the FITC-binding site was in the large (A) subunit
      of ATPase. Inhibition could be substantially prevented by its physiological
      substrate ATP, pyrophosphate and nucleotides in the decreasing order: ATP greater
      than pyrophosphate greater than ADP greater than AMP greater than GTP greater
      than CTP greater than UTP. The mode of inhibition by FITC was competitive with
      respect to ATP. Loss of ATPase activity followed pseudo-first-order kinetics with
      a Ki of 0.33 mM, a minimum inactivation half-time of 110 s, and a first-order
      rate constant of 0.244 s-1. A double-logarithmic plot of apparent rate constant
      versus FITC concentration gave a slope of 0.913, indicating that inactivation
      results from reaction of at least one lysine residue at the catalytic site of the
      large subunit. Labelling studies indicated that the incorporation of approx. 1
      mol of FITC/mol of ATPase is sufficient to inhibit ATPase completely. The
      enhancement and blue shift of emission maxima of FITC after modification of
      ATPase indicated that the labelled lysine residue was located in a relatively
      hydrophobic domain.

PMID- 1386734
TI  - Genetic evidence for an androgen-regulated epididymal secretory glutathione
      peroxidase whose transcript does not contain a selenocysteine codon.
AB  - Epididymal glutathione peroxidase (GPX) has been suggested as a major factor in
      combating loss of fertility of spermatozoa due to lipid peroxidation. We report
      here the isolation and sequence of putative GPX cDNAs from rat (Rattus rattus)
      and cynomolgus-monkey (Macaca fascicularis) epididymis, which exhibit marked
      sequence identity with known GPXs. In both species the cDNAs encode predicted
      preproteins containing 221 amino acid residues. Unlike other characterized GPX
      sequences, epididymal GPX mRNA does not contain a selenocysteine codon (UGA).
      However, sequence comparison and molecular-modelling studies suggest a high
      degree of structural conservation between epididymal and other GPXs. Transcripts
      corresponding to epididymal GPX are not detected in a variety of other tissues
      (liver, spleen, kidney and testis) and appear to be androgen-regulated in the
      epididymis.

PMID- 1386735
TI  - Nucleotide sequence, organization and characterization of the atp genes and the
      encoded subunits of Mycoplasma gallisepticum ATPase.
AB  - The nucleotide sequence of a 7.8 kbp DNA fragment from the genome of Mycoplasma
      gallisepticum has been determined. The fragment contains a cluster of nine
      tightly linked genes coding for the subunits of the M. gallisepticum ATPase. The
      gene order is I (I-subunit), B (a-subunit), E (c-subunit), F (b-subunit), H
      (delta-subunit), A (alpha-subunit), G (gamma-subunit), D (beta-subunit) and C
      (epsilon-subunit). Two open reading frames were identified in the flanking
      regions; one (ORFU), preceding the I gene, encodes at least 110 amino acids and
      the other (ORFS), following the C gene, encodes at least 90 amino acids. The
      deduced amino acid sequences of the various subunits are presented and discussed
      with regard to the structure, function and differing sensitivity of the M.
      gallisepticum enzyme to dicyclohexylcarbodiimide and aurovertin. The alpha- and
      beta-subunits of the F1 portion are well conserved (51% and 65% identity with
      those of Escherichia coli), whereas the gamma-, delta- and epsilon-subunits, as
      well as the F0-subunits, show a low percentage identity. Nonetheless, the
      secondary structure of the F0-subunits show a high degree of similarity to the
      corresponding subunits of E. coli. Two very strong potential amphipathic alpha
      helices are predicted in the delta-subunit and the N-terminus of the b-subunit
      contains two hydrophobic helical stretches. The possible roles of these
      structural properties in the close association of the F1 and F0 multisubunit
      complexes among mycoplasmas are discussed.

PMID- 1386736
TI  - High-level stable expression of recombinant 5-HT1A 5-hydroxytryptamine receptors
      in Chinese hamster ovary cells.
AB  - The human 5-hydroxytryptamine 5-HT1A receptor gene was transfected into Chinese
      hamster ovary cells. A series of recombinant monoclonal cell lines expressing the
      receptor were isolated and the properties of one cell line that expressed
      receptors at a high level (2.8 pmol/mg) were studied in detail. In ligand binding
      assays with the selective 5-HT1A receptor agonist 2-(NN-di[3H]propylamino)-8
      hydroxy-1,2,3,4-tetrahydronaphthalene ([3H]8-OH-DPAT) only a single class of
      saturable high-affinity binding sites was detected, with a pharmacological
      profile in competition experiments essentially identical to that of the 5-HT1A
      receptor of bovine hippocampus. [3H]8-OH-DPAT binding to the recombinant cell
      membranes was inhibited by GTP, showing that the receptors in the transfected
      cells couple to G-proteins. A series of 5-hydroxytryptamine agonists inhibited
      forskolin-stimulated adenylate cyclase activity in the cells and, despite the
      high level of receptor expression, their apparent efficacies were similar to
      those observed for inhibition of adenylate cyclase in brain. This recombinant
      cell line provides a complete model system for studying the 5-HT1A receptor and
      its transmembrane signalling system. The recombinant cells can also be grown in
      suspension culture for long periods but, whereas 5-HT1A receptor numbers and
      receptor regulation by guanine nucleotides are maintained in suspension-grown
      cells, the inhibition of adenylate cyclase by the 5-HT1A receptor is gradually
      lost.

PMID- 1386738
TI  - Stress related workers' compensation claims: recommendations involving records
      release.
AB  - 1. The cost of stress claims is predicted to cripple the workers' compensation
      system, where stress claims are burgeoning and the average payout is twice that
      of a typical injury. The major reason to release medical records in a stress
      claim is to determine the validity of the claim arising from the job. 2.
      Occupational health nurses are frequently asked by the courts to reveal personal
      client information and may not be protected by the "nurse-client relationship" or
      "privileged communication." Politically, very little interest has been shown in
      restricting disclosure of private information. 3. Both ANA and AAOHN have adopted
      strong positions about safeguarding privacy. Legally, the ultimate responsibility
      for wrongful acts committed by the nurse falls on the individual nurse. 4. The
      most important reason to guard confidential health information is the basic tenet
      of the nurse-client relationship in which personal matters are held in
      confidence. To break this trust is to jeopardize the ability to provide optimal
      client care, which is the essence of nursing.

PMID- 1386737
TI  - Association of annexin V with prolactin in the rat anterior pituitary gland.
AB  - When pituitary extracts were subjected to non denaturing polyacrylamide gel
      electrophoresis, an unknown protein was found to associate with a proportion of
      the prolactin. This protein was dissociated from prolactin by sodium dodecyl
      sulfate. The protein was purified and sequenced. As the amino terminus was
      blocked, the amino acid sequences of three peptide fragments were determined. The
      obtained sequences of 41 amino acids were identical to partial sequences of a
      known protein, rat Annexin V. The molecular mass, 36 kDa, was also the same as
      the molecular weight of Annexin V. The existence of Annexin V mRNA in rat
      pituitary glands was also confirmed by polymerase chain reaction. These results
      show that Annexin V, a member of the calcium-dependent phospholipid binding
      proteins, is synthesized in the rat pituitary gland, and suggest its association
      with prolatin in the gland.

PMID- 1386739
TI  - Needs expressed by mothers and fathers of young children with disabilities.
AB  - One aspect of family adaptation to a young child with disabilities was
      investigated through comparison of expressed needs of mothers and fathers and
      examination of the relation of those needs with selected child and family
      characteristics. A diverse sample of more than 400 parents completed the Family
      Needs Survey (Bailey & Simeonsson, 1988). A factor analysis of the items for
      mothers yielded six distinct factors. A confirmatory factor analysis of needs
      expressed by fathers indicated a structure that differed significantly from that
      found for mothers. Mothers expressed significantly more needs than did fathers.
      Although SES and disability type accounted for significant variance in needs of
      mothers, an examination of mean values suggested the effect to be of limited
      clinical significance.

PMID- 1386740
TI  - Relations between mothers' expectations and the performance of their infants who
      have developmental handicaps.
AB  - Relations between mothers' expectations and the performance of their infants with
      a disability on specific developmental tasks were explored. These mothers
      predicted their child's performance on developmental measures with accuracy
      levels comparable to those of parents of preschool children without disabilities.
      Children whose mothers were initially the most accurate in their estimations
      tended to show fewer gains in their statistically adjusted Bayley Mental
      Development Index scores over the course of the study. Mother's initial accuracy
      scores were found to account for substantial additional portions of the variance
      in the children's Bayley performances 14 and 28 weeks later.

PMID- 1386741
TI  - Object play and exploration in children with and without disabilities: a
      longitudinal study.
AB  - The development of object play was examined in 40 children (20 with and 20
      without disabilities). The children with disabilities were assessed at ages 11,
      15, 19, and 27 months; the children without disabilities, at 6, 11, 15, and 27
      months. At each assessment, the children were videotaped during 20 minutes of
      play with their mothers in a controlled environment. Child's play level was
      positively related to developmental age for the disabled group at each assessment
      and for the nondisabled group at 6, 11, and 15 months of age. The types of object
      play observed in children with no disabilities were observed in the children with
      disabilities at comparable developmental ages. In a subsample matched for
      developmental age, the duration and frequency of active involvement with objects
      were greater for the children without disabilities than for the children with
      disabilities.

PMID- 1386742
TI  - K-ABC profiles in children with fragile X syndrome, Down syndrome, and
      nonspecific mental retardation.
AB  - Etiology-specific profiles of intellectual abilities were compared in three
      groups of males with mental retardation using the Kaufman Assessment Battery for
      Children (K-ABC). Subjects included 10 males with fragile X syndrome, 10 with
      Down syndrome, and 10 with nonspecific mental retardation who were equated on
      both mental and chronological age. Across all three groups, sequential processing
      was lower than simultaneous processing or achievement, and particular subtests
      (e.g., Gestalt Closure) were relative strengths. Although boys with Down syndrome
      showed less extreme patterns of domain strengths and weaknesses, they showed a
      significant strength in the Sequential Processing Hand Movements subtest. In
      contrast, the Hand Movements subtest was lowest of all K-ABC subtests for males
      with fragile X syndrome. Implications were discussed for more fine-tuned research
      and intervention efforts.

PMID- 1386743
TI  - Hearing loss in middle-age persons with Down syndrome.
AB  - Hearing function of 35 institutionalized persons with Down syndrome, age 35 to 62
      years, was assessed by means of otoscopy, impedance audiometry, brainstem evoked
      response audiometry, and pure tone audiometry. Using brainstem evoked response
      audiometry, we determined response thresholds for 59 ears, which compares
      favorably with pure tone audiometry (20 ears). We found hearing losses of 20 dB
      to over 90 dB in 56 of these ears. Hearing loss should be considered and,
      whenever feasible, excluded as a contributing factor in social and mental
      deterioration in middle-age persons with Down syndrome.

PMID- 1386744
TI  - Mothers' and fathers' perceptions of stress and coping with children who have
      severe disabilities.
AB  - Stress in families with children who have special needs, which has been the focus
      of much research interest, is usually assessed solely from a maternal
      perspective. In this study, the short form of the Questionnaire on Resources and
      Stress (QRS-F, Friedrich, Greenberg, & Crnic, 1983) was completed separately by
      mothers and fathers of children with severe developmental disabilities. To
      compare responses of mothers and fathers, we employed factor analysis of parcels
      using the parallel analysis criterion rather than the more traditional item level
      analysis with minimum eigenvalue criterion. Results indicated that the QRS-F
      differed only slightly in both factor structure and correlates as a function of
      parental gender. Overall, validity of the QRS-F for use with both mothers and
      fathers of children with severe disabilities was supported.

PMID- 1386745
TI  - Delayed hydrophobic surfactant protein (SP-B, SP-C) expression in fetuses of
      streptozotocin-treated rats.
AB  - Tissues from fetuses and neonates of control and streptozotocin (STZ)-treated
      Sprague-Dawley rats were used to study the content and distribution of the
      hydrophobic surfactant protein B (SP-B) and the mRNAs for SP-B and SP-C using
      immunohistochemistry, RNA blotting, and tissue in situ hybridization. A dose of
      50 mg/kg STZ was used to treat female rats before mating. The fetuses were
      sacrificed at fetal days 18 through 21 and neonates were obtained on neonatal
      days 1 and 2 (day of birth = end of day 22). At fetal day 18, SP-B was barely
      detectable by immunohistochemistry in control animals but the levels were
      progressively increased through gestation and easily detected by fetal day 21. At
      all fetal ages, SP-B was decreased in the STZ group compared with control
      animals. Both SP-B and SP-C mRNA were detectable at fetal day 18 in the control
      group and increased with advancing gestational age. In fetal lungs from the STZ
      group, SP-B and SP-C mRNA also showed an increase with advancing gestational age,
      but the levels were decreased compared with controls at fetal days 18, 20, and 21
      (P less than 0.05). At fetal day 19, this difference did not achieve statistical
      significance. Differences between the two groups were no longer detected by
      neonatal days 1 and 2. The difference between the STZ and control groups, in both
      protein (SP-B) and mRNA (SP-B and SP-C), diminished with advancing fetal age but
      remained significant up to fetal day 21.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386746
TI  - Doppler color imaging. Peripheral arteries.
AB  - The impact of DCI on the evaluation of peripheral vascular disease is
      considerable. In essence, it is noninvasive angiography without the limitations
      of that modality. However, the pressure gradient can only be inferred, and pull
      through pressure gradients are still the most accurate estimation of adequacy of
      flow. Nonetheless, segmental blood pressures and the peak velocities measured by
      duplex Doppler provide a noninvasive alternative for estimating pressure
      gradients. DCI imaging has greatly improved the perception of focal abnormalities
      and allows rapid appreciation of global hemodynamics. As further technical
      refinements improve resolution and sensitivity, color Doppler may eventually
      supplant angiography as the primary imaging modality in peripheral arterial
      diagnosis, reserving arteriography for interventional procedures.

PMID- 1386747
TI  - Service needs of children with disabilities and their families.

PMID- 1386749
TI  - [A personal account. Via twisted ways toward burnout].

PMID- 1386748
TI  - Service needs of children with disabilities and their families.
AB  - A survey of 1527 families receiving the Child Disability Allowance was
      undertaken. There were substantial unmet needs for home help services, respite
      care and equipment. Satisfaction with services, particularly therapy, and respite
      care facilities was less than optimal. Many families also lacked knowledge about
      resources available to them. Improvement in the quality and availability of
      services is essential as is dissemination of information about available
      facilities.

PMID- 1386750
TI  - Update: dracunculiasis eradication, Ghana and Nigeria, 1991.

PMID- 1386751
TI  - Different accessory function for TH1 cells of bone marrow derived macrophages
      cultured in granulocyte macrophage colony stimulating factor or macrophage colony
      stimulating factor.
AB  - The ability of macrophages to stimulate immune responses is heterogeneous and may
      have influence on the type of the developing immune response. Therefore, in an
      attempt to define different functional states of mouse macrophages, we made use
      of the two macrophage growth factors: macrophage colony stimulating factor (M
      CSF) and granulocyte macrophage colony stimulating factor (GM-CSF). Generation of
      macrophages from freshly isolated bone marrow cells in the presence of GM-CSF
      results in a population expressing profound antigen presenting function for mouse
      TH1 cells, resulting in strong lymphokine production and proliferation of the T
      cells. Furthermore, high amounts of a novel soluble cytokine active on mouse TH1
      cells are generated during the interaction of TH1 cells with macrophages elicited
      with GM-CSF. In contrast, macrophages grown from bone marrow cells for at least
      14 days in the presence of M-CSF express only minimal antigen-presenting function
      for TH1 cells. Treatment of such macrophages for 24 h with either IFN-gamma or GM
      CSF allows the distinction between two further functional states. Those treated
      with IFN-gamma efficiently presented antigen towards TH1 cells. The T cells
      produced large amounts of lymphokines and proliferate well. However, synthesis of
      the novel soluble cytokine (active on TH1 cells) was not detectable. The
      generation of this mediator requires a short-term treatment with GM-CSF of
      macrophages developed in the presence of M-CSF prior to their interaction with
      TH1 cells.

PMID- 1386752
TI  - A successful regimen for the prevention of seroconversion after transplantation
      of a heart positive for hepatitis B surface antigen.
AB  - We report a case involving orthotopic heart transplantation in which a recipient,
      known to be serologically negative for hepatitis B virus infection, received a
      heart from a donor known before transplantation to be hepatitis B surface antigen
      positive. The recipient was treated prospectively with a combination of hepatitis
      B immune globulin and hepatitis B vaccine. After 10 months of follow-up, the
      recipient has not experienced seroconversion or viremia from hepatitis B virus
      and has remained without symptoms by both clinical and laboratory measurements.

PMID- 1386753
TI  - Circadian rhythms of heart rate and blood pressure after heart transplantation.
AB  - Blood pressure and heart rate were recorded over 24-hour periods on 39 occasions
      in 20 subjects 5 to 72 weeks after heart transplantation. All patients were
      receiving cyclosporine, azathioprine, and prednisolone. In 38 of the 39 records
      the mean nighttime heart rate was lower than the mean daytime rate, with a peak
      difference of 20.1 +/- 1.8 beats/min. Blood pressure responses were, however, of
      two patterns. In 15 of the 39 recordings (approximately 50% of patients) the mean
      nighttime systolic pressure was higher than the mean daytime systolic pressure;
      in the remainder the converse was observed. The pattern was generally consistent
      on repeated recordings from the same patient and was not related to time since
      transplantation, renal function, or other therapy. Echocardiographic/Doppler
      studies were available at the time of 31 of these recordings. No differences in
      left ventricular diameters, systolic function, or transmitral filling patterns
      were present between patients whose blood pressure was higher or lower at night.
      Left ventricular posterior wall thickness and the ratio between wall thickness
      and ventricular diameter at end diastole were greater in the group showing
      nighttime pressure falls. Blood pressure responses after heart transplantation
      show the presence of nighttime "dippers" and "nondippers." At least early after
      transplantation, however, nondipper status is not preferentially associated with
      the development of left ventricular hypertrophy. The mechanisms accounting for
      the different circadian blood pressure responses in heart transplant recipients
      are not known.

PMID- 1386754
TI  - Laparoscopic cholecystectomy in the heart transplant candidate with acute
      cholecystitis.
AB  - We report the first successful laparoscopic cholecystectomy for treatment of
      acute cholecystitis in a heart transplant candidate with end-stage heart disease.
      Eight successful cases of conventional cholecystectomy in heart transplant
      candidates have been reported, but convalescence after the conventional procedure
      is prolonged, and morbidity often interferes with a timely heart transplantation.
      Laparoscopic cholecystectomy is a less-invasive method for treatment of
      symptomatic cholelithiasis and cholecystitis and may be better tolerated in this
      patient population. Although further study is needed, we believe laparoscopic
      cholecystectomy will have applications in patients with end-stage heart disease.

PMID- 1386755
TI  - Optimized radiotherapy for head and neck cancer.
AB  - Optimization of radiation therapy for head and neck tumors requires the
      combination of several facets of radiation biology and physics. The aim is to
      achieve optimum tumor control while reducing normal tissue damage. Techniques
      have been developed to determine tumor radiosensitivity and growth
      characteristics. Their use as predictive assays of treatment response is gaining
      importance. As the range of therapeutic options (particularly altered
      fractionation regimens) increases, it is hoped that the ability to individually
      tailor patients' treatment will result in improved rates of tumor control and an
      improved therapeutic ratio. Optimization of treatment delivery based on three
      dimensional treatment planning offers the opportunity for dose escalation studies
      and limitation of normal tissue morbidity. The combination of chemotherapy and
      radiotherapy continues to be investigated, although major advances using this
      strategy are unlikely.

PMID- 1386756
TI  - Binding and internalization of the 163-171 fragment of human IL-1 beta.
AB  - The mechanisms of cell association of the human interleukin (IL-1 beta)
      immunostimulatory fragment 163-171 have been studied. The fragment was able to
      associate abundantly to both IL-1R- and IL-1R+ cells. Binding was strictly
      temperature dependent, was not saturable and could be inhibited by excess amounts
      of unlabelled 163-171 peptide but not by IL-1 beta, suggesting that the 163-171
      fragment is not an IL-1R-binding domain of IL-1 beta. The fragment is readily
      internalized by cells by a cytochalasin-insensitive mechanism and it localizes
      mainly in the cytoplasm. It is concluded that the active domain 163-171 of IL-1
      beta can be taken up by cells through a receptor-independent, temperature
      dependent mechanisms and that its ability to activate cellular functions is based
      on IL-1R-independent intracellular pathways.

PMID- 1386757
TI  - Both naive and memory T cells can provide help for human IgE production, but with
      different cytokine requirements.
AB  - Most in vitro systems for the induction of IgE production by human B cells
      require both IL-4 and the presence of T cells. Little is known about the
      mechanism of T cell help or the ability of different T cell subsets to provide
      this helper activity. In the present study we demonstrate that, in the presence
      of exogenous IL-4, anti-CD3 stimulated naive T cells (CD4+CD45RA+) are potent
      helper cells for human IgE production. In their presence, as little as 750
      autologous B cells can produce up to 100 ng/ml IgE. This response was found over
      a broad range of anti-CD3 concentrations. IgE helper activity by naive T cells
      was inhibited by IL-2. Under all conditions tested, naive T cells were unable to
      provide help for IgM production. This is in contrast to activated memory T cells
      (CD4+CD45RO+), which are very efficient helper cells for IgM or IgE production,
      provided that IL-2 or IL-2 plus IL-4 are present respectively.

PMID- 1386758
TI  - Impaired atrial natriuretic factor systemic clearance contributes to its higher
      levels in uremia.
AB  - To evaluate the interaction between plasma levels and the systemic uptake of
      atrial natriuretic factor (ANF) with thyroid hormone levels during acute renal
      failure (ARF), seven groups of rats were analyzed: Group 1, Controls (C); Group
      2, ARF; Group 3, filtering kidney with uremia; Group 4, ARF with thyroxine (T4)
      supplement (ARF + T4); Group 5, thyroidectomy (Tx); Group 6, ARF on Tx rats (Tx +
      ARF); Group 7, Tx + ARF supplemented with T4 (Tx + ARF + T4). Plasma creatinine
      (Cr), urea, T4, blood volume, and ANF were measured; ANF half-life (ANF t1/2;
      expressed in seconds) was calculated. Rats with ARF developed uremia (Cr, 377 +/-
      58 versus 41 +/- 5 mumol/L), significant reduction in T4 (40 +/- 4 versus 89.2 +/
      6 nmol/L). elevation of ANF (287.7 +/- 35 versus 60.9 +/- 8 fmol/mL), and
      lengthening of ANF t1/2 (69.7 +/- 8 versus 37.2 +/- 6 s) compared with C (P less
      than 0.01). T4 supplements to ARF rats resulted in a lesser degree of uremia (Cr,
      283 +/- 27; P less than 0.05) and normalization of ANF t1/2 (31.4 +/- 5);
      however, ANF levels remained higher than C (100.4 +/- 11.4 versus 60.9 +/- 8; P
      less than 0.01). Tx by itself did not change either parameter. The filtering
      kidney with uremia group developed mild uremia (Cr, 199 +/- 8), T4 fell (58 +/-
      8), ANF levels rose (83.4 +/- 5.4), and ANF t1/2 was prolonged (54.5 +/- 12). Tx
      before ARF doubled the ANF level and lengthened ANF t1/2 similarly than in ARF.
      T4 addition (Tx + ARF + T4) normalized ANF t1/2 (29.8 +/- 3) in spite of a
      persistently high ANF (145.7 +/- 21). Blood volume did not change in any
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386759
TI  - Interleukin-1 regulates cytokine gene expression in human mesangial cells through
      the interleukin-1 receptor type 1.
AB  - We have recently shown that interleukin-1 is a potent stimulus of gene expression
      and production of leukocyte chemotactic factors, colony-stimulating factors, and
      interleukin-6 in human mesangial cells in culture. Here, we sought to determine
      whether interleukin-1 induces its own gene expression in human mesangial cells.
      Interleukin-1 mRNA levels were quantitated by Northern blot analysis with total
      cellular RNAs isolated from human mesangial cells exposed for 6 h to medium alone
      or in the presence of human recombinant interleukin-1 beta (1 to 100 ng/mL).
      Interleukin-1 induced interleukin-1 mRNA expression in a dose-dependent manner.
      An additional finding of this study was that human mesangial cells constitutively
      express the 80 kd interleukin-1 receptor type 1 gene. When human mesangial cells
      were exposed to interleukin-1, interleukin-1 receptor expression was not
      modified. Similarly, other stimuli like tumor necrosis factor, transforming
      growth factor beta, or interleukin-6 did not modulate interleukin-1 receptor
      expression. Recombinant interleukin-1 receptor antagonist blocked the interleukin
      1 mRNA as well as interleukin-6 and interleukin-8 mRNA accumulation induced by
      interleukin-1 beta. Lipopolysaccharide, which is a known stimulus for interleukin
      1 transcription in several cell types, also induced interleukin-1 mRNA
      accumulation, thus indicating that lipopolysaccharide mediates interleukin-1 gene
      activation in human mesangial cells through an interleukin-1-independent pathway.
      These data support the pivotal role of interleukin-1 in regulating mesangial cell
      cytokine genes and may be taken to indicate the existence of an interleukin-1
      mediated positive feedback loop that might control the secretion of active
      cytokines within the glomeruli when an immunological or inflammatory injury takes
      place.

PMID- 1386760
TI  - Intraoperative echocardiography for diagnosis of unsuspected hypertrophic
      cardiomyopathy.

PMID- 1386761
TI  - Patterns of membrane CD45 isoform expression by leukaemic blasts and normal
      mature myeloid cells.
AB  - The membrane expression of CD45R isoforms by leukaemic blasts from 92 cases of
      acute myeloid (AML) and 12 cases of lymphoblastic leukaemia was analysed by
      single and two-colour flow cytometry. Compared to normal mature granulocytes,
      which invariably expressed UCHL1 (CD45RO) but not 2H4 (CD45RA), leukaemic myeloid
      blasts showed 2H4+ UCHL1- and 2H4- ++UCHL1- composite patterns of expression with
      the first of these phenotypes being associated in particular with the most
      immature AML subtype (M0). Similar analyses of blast cell fractions from
      monocytic AML variants, revealed wide variation in CD45R expression in cases of
      M4, whereas M5 leukaemias were typically 2H4+ ++UCHL1+ with minor 2H4- UCHL1-
      components. As most normal mature monocytes were also 2H4+ ++UCHL1+, this
      suggested that monocytic myeloid differentiation was primarily associated with
      the "acquisition" of UCHL1 and the development of 2H4/UCHL1 co-expressing cells.
      The expression of membrane CD45RA by leukaemic blasts is an abnormal
      characteristic and may be related to the maintenance of an undifferentiated state
      by malignant myeloid precursors.

PMID- 1386762
TI  - Effect of interleukin-11 on cycling status and clonogenic maturation of fetal and
      adult hematopoietic progenitors.
AB  - A recently cloned human cytokine, interleukin-11 (IL-11), has functional
      similarities to IL-6. We tested the hypothesis that the hematopoietic actions of
      IL-11 in vitro also resemble those of IL-6. The effect of IL-11 on the cell cycle
      status of fetal and adult hematopoietic progenitors was assessed using serum-free
      incubations followed by tritiated thymidine suicide studies. Its effect on
      clonogenic maturation was assessed by including IL-11, either as a single agent
      or with subplateau or plateau concentrations of other recombinant cytokines, in
      cultures that contained neutralizing monoclonal antibodies directed against
      relevant growth factors. Similar to IL-6, IL-11 resulted in accelerated cycling
      of fetal colony-forming units-mixed (CFU-MIX), CFU-granulocyte macrophage (CFU
      GM), and erythroid burst-forming units (BFU-E). This effect was additive to that
      of submaximal, but not to plateau, concentrations of IL-6. However, no effect of
      IL-11 was observed on cycling status of adult progenitors. As a single agent, IL
      11 failed to support clonal maturation of either fetal or adult progenitors. IL
      11 was additive to GM-CSF in supporting clonal maturation of CFU-GM from adult
      marrow but not from fetal blood. We conclude that the in vitro hematopoietic
      actions of IL-11 on cell cycle status of hematopoietic progenitors resemble those
      of IL-6. However, unlike IL-6, IL-11 as a single agent failed to support clonal
      maturation of fetal CFU-GM, BFU-E, and CFU-MIX.

PMID- 1386763
TI  - Efficient clodronate entrapment within multilamellar and unilamellar liposomes.
AB  - Clodronate (dichloromethylene bisphosphonate) encapsulated within liposomes and
      administered intravenously eliminates resident macrophages within the liver and
      spleen. Macrophage depletion in the rat requires 20 mg of the encapsulated drug,
      and so far this has only been achieved using large multilamellar vesicles (MLV).
      Recent studies have shown that small unilamellar vesicles (SUV) when injected
      intravenously accumulate at inflamed joint sites in both animal models of
      arthritis and patients with rheumatoid arthritis; multilamellar vesicles were not
      able to do so. If phagocytic cells, such as macrophages, are responsible for SUV
      sequestration, then SUV containing clodronate may be targeted to the inflamed
      joint and may eliminate the macrophage population leading to reduction in the
      state of inflammation. We have adapted an existing technique to radiolabel
      clodronate with 99mTechnetium to use as a tracer to determine its encapsulation
      within liposomes, a technique that has advantages over other current methods. We
      have achieved a high-encapsulation efficiency of the drug within MLV and produced
      SUV containing sufficient clodronate to deplete macrophages in rats in a small
      enough volume to administer it intravenously as a single dose.

PMID- 1386765
TI  - Thyrotoxicosis presenting as generalized pruritic exfoliative dermatitis and
      fever.

PMID- 1386764
TI  - Activation of the p34 CDC2 protein kinase at the start of S phase in the human
      cell cycle.
AB  - Using a protocol for selecting cells on the basis of both size and age (with
      respect to the preceding mitosis), we isolated highly synchronous human G1 cells.
      With this procedure, we demonstrated that the p34 CDC2 kinase was activated at
      the start of S phase. Cyclin A synthesis began at the same time, and activation
      of the p34 CDC2 kinase at the start of S phase was, at least in part, due to its
      association with cyclin A. Furthermore, cells synchronized in late G1 by exposure
      to the drug mimosine contain active cyclin A/p34 CDC2 kinase, indicating that p34
      CDC2 activation can occur before DNA synthesis begins. Thus, the cyclin A/CDC2
      complex, which previously has been shown to be sufficient to start SV40 DNA
      synthesis in vitro, assembles and is activated at the start of S phase in vivo.

PMID- 1386766
TI  - Comparative study of ketoconazole 2% foaming gel and betamethasone dipropionate
      0.05% lotion in the treatment of seborrhoeic dermatitis in adults.
AB  - Sixty-two patients with seborrhoeic dermatitis were treated topically with a 2%
      ketoconazole foaming gel or with a 0.05% betamethasone dipropionate lotion in a
      single-blind study for 4 months. Changes in the number of Pityrosporum ovale were
      scored by a mycologist. The investigator rated the severity of erythema, scaling
      and itching of the patients' scalp, eyelashes, nasolabial folds and thorax. In
      addition, both the investigator and the patients evaluated the treatments
      globally. At the end of treatment, the response rate for ketoconazole 2% foaming
      gel was significantly higher than that for betamethasone dipropionate 0.05%
      lotion according to the global evaluation by the physician (89 vs. 62%, p less
      than 0.05) and the patient (89 vs. 65%, p less than 0.05). Ketoconazole was also
      superior to betamethasone with reference to the evolution of the symptoms,
      irrespective of their localization. This efficacy manifested itself by a
      significant reduction of the number of P. ovale on the scalp in the ketoconazole
      group (p less than 0.001) compared to the betamethasone group, in which the count
      was hardly changed during therapy. The treatment was also better tolerated in the
      ketoconazole group (5 vs. 16 patients with side-effects, p less than 0.001). It
      is concluded that ketoconazole 2% foaming gel offers an excellent alternative to
      local corticosteroids in the treatment of seborrhoeic dermatitis.

PMID- 1386767
TI  - Refractory peptic ulcers.
AB  - Ulcers that do not heal after 8 weeks of treatment with standard-dose regimens of
      antiulcer drugs are considered refractory. Incidences of duodenal and gastric
      ulcers refractory to H2-receptor antagonists are 9% and 20%, respectively. When
      treated with a single daily dose of omeprazole 20 mg, duodenal ulcers have a
      refractory incidence of 3% and gastric ulcers, 11%. Omeprazole's benefit may
      result from its potent gastric antisecretory action. Acid hypersecretion is an
      important pathophysiologic factor associated with refractoriness to H2
      antagonists. Some patients with refractory ulcer, however, have a normal
      pharmacologic response of decreasing intragastric acidity following
      administration of H2 antagonists. Two possible mechanisms may explain
      refractoriness in such cases: the relative preservation of daytime acidity, which
      is the usual pharmacologic response to standard doses of H2 antagonists, and
      excessive impairment of mucosal defense. The first possibility is consistent with
      the results that increased doses of H2 antagonists or more potent antisecretory
      drugs such as omeprazole do heal a subgroup of ulcers refractory to H2
      antagonists. The second possibility is supported by reports that drugs that
      mainly enhance mucosal defense, such as misoprostol, sucralfate, and bismuth
      compounds, also effectively heal refractory ulcers, and that gastrointestinal
      prostaglandin levels are extremely low in the mucosa of such patients. Other
      reasons for refractoriness to omeprazole treatment include gastric hyperacidity
      and impaired gastric emptying that may disturb drug absorption. Infection with
      Helicobacter pylori might, to some extent, be involved in refractoriness to
      potent antisecretory drugs. Single daily doses of omeprazole 40 mg seem superior
      to omeprazole 20 mg or increased doses of H2 antagonists for maintenance therapy
      of H2 antagonist-refractory ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386768
TI  - [Syndrome differentiation in traditional Chinese medicine in chronic aplastic
      anemia; T-lymphocyte subpopulation in peripheral blood and erythrocyte C3b
      receptors].
AB  - In this paper, the Syndrome Differentiation in TCM and the determination on T
      lymphocyte subpopulation and RBC C3b receptor were carried out by using indirect
      SPA assay and RBC C3b receptor ring test among 51 chronic aplastic anemia
      patients. RESULT: The OKT3, OKT4 and OKT4/OKT8 ratio in groups of Kidney-Yin
      Deficiency group were lower, while the OKT8 was higher than that of controls. In
      the group of both Kidney-Yin and Yang Deficiency, OKT4 and OKT4/OKT8 ratio were
      lower. and the value of OKT8 is higher than that of controls. The OKT8 in the
      Kidney-Yang Deficiency group was higher. and the ratio of OKT4/OKT8 was lower
      than that of controls. The OKT8 in the Kidney-Yin Deficiency group among three
      groups increased higher than that of other two groups. while the OKT4/OKT8 ratio
      reduced. The OKT4/OKT8 ratio in the group of both Kidney-Yin and Yang Deficiency
      was higher than that of Kidney-Yang Deficiency group. Among the three groups, the
      rosette rates of RBC C3b receptor were lower than controls. The above-mentioned
      data were statistically significant. These characteristic changes could be used
      as a reference of microcosmic Syndrome Differentiation and also a guide for how
      to apply the immunosuppressant and immunopotentiator.

PMID- 1386769
TI  - New polyolefin foil for 5-day storage of platelet concentrates (PC) collected by
      apheresis.
AB  - In a paired study 12 platelet concentrates (PC) of Fresenius AS-104 cell
      separator were stored in new polyolefin bags of Fresenius (LE2) and Fenwal PL-732
      bags. On day 0 and after 3 and 5 days of storage pH, pO2, pCO2, cell counts,
      platelet morphology and aggregability, plasma glucose, lactate, LDH and beta TG
      were determined. The overall changes fell within the expected range. No relevant
      differences between the two bags could be detected, although a few parameters
      (pH, pCO2) are slightly but statistically/significantly different. It can be
      concluded that the new polyolefin bag is well suited for 5-day storage of PC's
      from the AS-104.

PMID- 1386770
TI  - Progressive slowing of reaction time and increasing cerebrospinal fluid
      concentrations of quinolinic acid in HIV-infected individuals.
AB  - Neuropsychological functioning and cerebrospinal fluid concentrations of an
      endogenous neurotoxin, quinolinic acid (QUIN) were evaluated in 52 HIV-positive
      individuals (71% without constitutional symptoms) and 33 HIV-seronegative
      controls (including 15 psychiatric patients with adjustment disorders). Although
      the HIV-positive subjects did not differ from controls on standard
      neuropsychological tests, simple and choice reactions times (RT) were slow at
      initial evaluation (P less than 0.01) and became progressively slower at 6-month
      re-evaluation (P less than 0.05). Cerebrospinal fluid (CSF) QUIN was elevated at
      initial evaluation and increased during the 6-month interval (P less than 0.05).
      Moreover, during this 6-month interval, progressive slowing of RT was highly
      correlated with increasing levels of CSF QUIN (r = 0.85, df = 15, P less than
      0.0001) but not with changes in mood, constitutional symptoms, or CD4 cell count.
      These findings suggest that RT may provide a sensitive behavioral measure of
      relatively early central nervous system involvement in HIV-infected individuals
      and that QUIN may play an important role in the pathogenesis of HIV-related
      neurological dysfunction.

PMID- 1386771
TI  - The NMDA receptor antagonist MK-801 does not protect against serotonin depletions
      caused by high doses of DL-fenfluramine.
AB  - The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine
      (MK-801) has been shown to block methamphetamine (MA) induced damage to the
      dopamine (DA) and serotonin (5HT) systems of the brain. DL-Fenfluramine (FEN) is
      another potential neurotoxin but its long-term depletions are more selective to
      the 5HT system. To determine whether MK-801 protects against damage induced by
      FEN, we treated rats with FEN (4 injections of 12.5 mg/kg, at 1 h intervals) in
      conjunction with either saline or MK-801 (2 injections of 2.5 mg/kg, administered
      15 min before and 90 min after the first FEN injection). Two weeks post
      treatment, MK-801 alone caused a small but significant decrease in 5HT tissue
      concentrations in striatum and amygdala. FEN significantly reduced 5HT in all 8
      brain regions studied. MK-801 + FEN did not protect against FEN-induced 5HT
      depletions in nucleus accumbens/olfactory tubercle, septum, frontal cortex,
      somatosensory cortex or hippocampus. MK-801 + FEN enhanced 5HT depletions in
      striatum, hypothalamus and amygdala. The differential protective effect of MK-801
      between MA and FEN are discussed in terms of a possible dopaminergic mechanism.

PMID- 1386772
TI  - Involvement of glycine site associated with the NMDA receptor in hippocampal long
      term potentiation and acquisition of spatial memory in rats.
AB  - The effects of 7-chlorokynurenic acid (7-Cl-Kyn), a selective antagonist at the
      glycine site associated with the N-methyl-D-aspartate (NMDA) receptor, on
      hippocampal long-term potentiation (LTP) and behavioral performances in a spatial
      learning task were investigated. Extracellular recordings of evoked potential
      (population spike) were made in rat hippocampal slices. Perfusion of 7-Cl-Kyn
      (10(-5) M) inhibited the induction of LTP following a tetanic stimulation (51 or
      101 pulses at 100 Hz) both in the Schaffer/commissural-CA1 pyramidal cell
      synapses and in the perforant path-dentate granule cell synapses. Acquisition of
      a spatial memory in the Morris water maze was examined using rats chronically
      cannulated for application of drugs. The intact and vehicle-injected rats learned
      easily to escape onto a hidden platform with short latencies, while the rats
      given an injection of 7-Cl-Kyn (10(-8) mol/brain, i.c.v.) prior to every session
      took a longer time and a longer path to escape even after all 5 sessions of
      trials. Injection of 7-Cl-Kyn did not affect the swimming speed, an index of
      swimming ability. This is the first report providing direct evidence that
      endogenous glycine supports the processes of learning and memory.

PMID- 1386773
TI  - DNABIND: an interactive microcomputer program searching for nucleotide sequences
      that may code for conserved DNA-binding protein motifs.
AB  - This paper presents a simple program for interactive searching for nucleotide
      sequences that may code for the helix-turn-helix, zinc finger or leucine zipper
      motifs in proteins. The helix-turn-helix motifs are predicted using the recently
      published method of Dodd and Egan, while zinc fingers and leucine zippers are
      searched for by our original methods. DNABIND is shown to detect all four known
      helix-turn-helix motifs in bacteriophage lambda genes and both zinc fingers of
      the adr1 gene of yeast.

PMID- 1386774
TI  - The superficial buffer barrier in vascular smooth muscle.
AB  - Force development and fura-2 fluorescence were simultaneously measured in the
      rabbit inferior vena cava. Discharging SR Ca2+ with either caffeine or
      norepinephrine prior to stimulation of Ca2+ influx induced a delay of 30-70 s
      between the intracellular Ca2+ signal and development of force. This delay was
      abolished by the application of caffeine. These data support the superficial
      buffer barrier hypothesis, which holds that Ca2+ entry from the extracellular
      space proceeds via a restricted cytoplasmic region between the inner plasmalemmal
      surface and the peripheral sarcoplasmic reticulum (SR). Ca2+ accumulation by this
      SR fraction appears to be able to delay Ca2+ entry into the deeper myoplasm where
      it activates the myofilaments. Caffeine and thapsigargin elevated the steady
      state [Ca2+]i, suggesting a contribution by the SR Ca2+ pump to Ca2+ extrusion
      from the cells. Norepinephrine enhanced myofilament Ca2+ sensitivity, while
      caffeine decreased it.

PMID- 1386775
TI  - Dietary sodium induced cardiac hypertrophy.
AB  - In humans, high sodium intake not only increases the blood pressure, and thus can
      cause left ventricular hypertrophy (LVH), but also appears to increase LVH
      independent of this increase in blood pressure. In both normo- and hyper-tensive
      rats the hypertrophic effect of increased dietary sodium intake on the heart has
      been clearly established. In normotensive rats, this effect is strain and age
      dependent, and seems independent of hemodynamic effects of high sodium intake. In
      both rats and humans, dietary sodium appears to increase wall thickness,
      resembling pressure overload rather than an increased left ventricular diameter
      as expected of volume overload. The mechanisms through which high dietary sodium
      induces hypertrophy are still unknown. It is possible that dietary sodium
      increases either adrenergic stimulation and (or) enhances sensitivity for
      adrenergic stimulation and that this hypertrophic response mainly acts via
      stimulation of alpha 1-adrenergic receptors. Stimulation of the alpha 1
      adrenergic receptors will increase the inositol phosphate-diacyl glycerol pathway
      and enhance the Na+/H+ exchange. The activity of this exchanger might play an
      important role in the development of dietary sodium induced cardiac hypertrophy.

PMID- 1386776
TI  - Laparoscopic cholecystectomy.

PMID- 1386777
TI  - Alleged link between hepatitis B vaccine and chronic fatigue syndrome.

PMID- 1386779
TI  - Update of the serotonergic hypothesis of obsessive compulsive disorder.

PMID- 1386780
TI  - The differential therapeutic outcome in schizophrenia of compounds acting at D2
      receptors.

PMID- 1386778
TI  - Steroid therapy for croup in children admitted to hospital. Infectious Diseases
      and Immunization Committee, Canadian Paediatric Society.

PMID- 1386782
TI  - Social signalling and schizophrenia: the significance of neurochemical and
      morphological abnormalities of the basolateral circuit.

PMID- 1386781
TI  - Ligand selection for PET studies of D1 dopamine receptors. Relationship between
      distribution of binding sites and mRNA for DAARPP32 in the human brain.

PMID- 1386783
TI  - Role of interleukin-1 receptors in the brain-endocrine-immune axis.

PMID- 1386784
TI  - NMDA and non-NMDA receptor mediated synapses in cortex.

PMID- 1386785
TI  - The NMDA macromolecular complex as a target for the development of anti-ischemic
      drugs.

PMID- 1386786
TI  - Theoretical and practical considerations concerning the use of NMDA antagonists
      in the treatment of the epilepsies.

PMID- 1386787
TI  - Enzymatic synthesis of low molecular weight amyloses with modified terminal
      groups.
AB  - Low molecular weight amyloses with modified terminal groups were synthesized by
      cyclomaltohexaose (alpha-cyclodextrin) transfer using (1----4)-alpha-D-glucan: 4
      alpha-D-(1----4)- alpha-D-glucopyranosyltransferase (cyclising) (EC 2.4.1.19)
      from Bacillus macerans. 4-Nitrophenyl alpha-malto-oligosaccharides d.p. 2-7
      served as acceptors, and cyclomaltohexaose served as the donor. The reaction was
      optimized to obtain a majority of species of definite chain lengths in a range of
      d.p. 10-20, depending upon the chain length of the acceptor. The course of the
      coupling reactions, as well as the action of the enzyme in disproportionation,
      cyclisation, and hydrolysis of the products, were observed by h.p.l.c. analysis
      of the oligomer distributions. Using a 15-fold molar excess of cyclomaltohexaose
      and 0.5 units enzyme per mumol of acceptor at pH 5.2, the chromatograms revealed
      that the products of the coupling reaction were predominant during the first
      reaction period. By incubating the acceptors with the enzyme, but without the
      donor, the mechanism of disproportionation was elucidated as a transfer of malto
      oligosaccharyl residues dependent upon the substrate chain length. The minimum
      chain length required for a direct cyclisation reaction was d.p. 7. The results
      were confirmed by separation and investigation of the products of hydrolysis and
      cyclisation, which were nonmodified alpha-malto-oligosaccharides and cyclomalto
      oligosaccharides.

PMID- 1386788
TI  - Elongation of both branches of biantennary backbones of oligo-(N
      acetyllactosamino)glycans by human serum (1----3)-N-acetyl-beta-D-
      glucosaminyltransferase.
AB  - Partial reactions catalyzed by a (1----3)-N-acetyl-beta-D-
      glucosaminyltransferase (EC2.4.1.149), known to be present in human serum, were
      studied by use of biantennary "backbone" saccharides of oligo-N-acetyllactosamine
      type as acceptors. Incubation of the radiolabeled blood-group I-active
      hexasaccharide, beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-[beta-D-Galp- (1---
      4)-beta-D-GlcpNAc-(1----6)]-beta-D-Galp-(1----4)-D-GlcNAc (1) and UDP-GlcNAc with
      serum gave first a transient 1:1 mixture of two isomeric heptasaccharides, beta-D
      GlcpNAc-(1----3)-beta-D-Galp-(1----4)-beta-D- GlcpNAc-(1----3)-[beta-D-Galp-(1---
      4)-beta-D-GlcpNAc-(1----6)]-beta-D- Galp-(1----4)-D-GlcNAc (2) and beta-D-Galp-(1
      ---4)-beta-D-GlcpNAc-(1----3)-[beta-D-GlcpNAc-(1----3)- beta-D-Galp-(1----4)-beta
      D-GlcpNAc-(1----6)]-beta-D-Galp-(1----4)-D-Glc NAc (3), showing that both
      branches of 1 react equally well. The two heptasaccharides reacted further in the
      incubation mixture to form the radiolabeled octasaccharide, beta-D-GlcpNAc-(1---
      3)-beta-D-Galp-(1----4)-beta-D-GlcpNAc-(1----3)-[be ta-D- GlcpNAc-(1----3)-beta-D
      Galp-(1----4)-beta-D-GlcpNAc-(1----6)]-beta-D-Ga lp- (1----4)-D-GlcNAc (4);
      during this second reaction, the composition of the heptasaccharide mixture
      remained unchanged, indicating that 2 and 3 reacted at approximately equal rates.
      The heptasaccharides 2 and 3 could not be separated from each other, but they
      could be detected, identified, and quantitatively determined by stepwise enzymic
      degradations. Partial (1----3)-N-acetyl-beta-D-glucosaminylation reactions,
      carried out with another acceptor, the branched pentasaccharide, beta-D-Galp-(1--
      -4)-beta-D-GlcpNAc-(1----3)-[beta-D-Galp-(1----4)-beta- D- GlcpNAc-(1----6)]-beta
      D-Gal (11), revealed that it reacted also equally well at both branches.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1386789
TI  - Molecular modelling of acarviosine, the pseudo-disaccharide moiety of acarbose,
      and other inhibitors of alpha-amylases.
AB  - Acarbose and its homologs inhibit alpha-D-glucosidases, particularly alpha
      amylases. These homologs have the same core, the pseudo-disaccharide acarviosine,
      linked to various numbers of glucose residues. The conformations of (R)- and (S)
      acarviosine have been analysed. The potential energy maps, obtained by molecular
      mechanics calculations, show that acarviosine is flexible and has several
      important minima. One low-energy form is close to the shape assumed by the
      acarviosine moiety when acarbose is adsorbed on the surface of glycogen
      phosphorylase. Another likely conformation is the same as that inferred from
      n.m.r. data and HSEA calculations. The results reconcile those conflicting
      reports. Molecular modelling of other inhibitors of alpha-amylases, such as 4
      thiomaltose and moranoline, shows that these pseudo-disaccharides can fill
      similar volumes of conformational space.

PMID- 1386791
TI  - A technique to access severely diseased arteries.
AB  - Cardiac catheterization performed in patients with severe peripheral vascular
      disease may represent a difficult technical challenge and is associated with a
      higher incidence of vascular complications. We describe a technique that uses
      angioplasty equipment to access severely diseased arteries. This technique allows
      a percutaneous transluminal coronary angioplasty (PTCA) guide wire to be steered
      across vascular lesions under direct visualization of the lumen and continuous
      pressure monitoring, potentially reducing the risk of vascular complications.

PMID- 1386793
TI  - Bacteriophage lambda DNA fragments replicate in the Paramecium macronucleus:
      absence of active copy number control.
AB  - We show that bacteriophage lambda DNA fragments microinjected into the
      macronucleus of the ciliated protozoan Paramecium can replicate as unit-length
      linear molecules. These linear DNA molecules are substrates for the addition of
      Paramecium telomeres by an endogenous telomerase. The linear DNA pieces can exist
      at copy numbers much higher than that of typical endogenous macronuclear
      chromosomes. We show that the copy number of injected DNA many fissions after
      microinjection reflects that of the original input copy number, suggesting that
      active control of copy number does not occur. Instead, the results suggest that
      injected DNA is replicated once per cell division.

PMID- 1386790
TI  - CGRP-immunoreactive endocrine cell proliferation in normal and hypoxic rat lung
      studied by immunocytochemical detection of incorporation of 5'-bromodeoxyuridine.
AB  - We have tested the suggestion that the reported increase, in hypoxic rats, in the
      number of lung endocrine cells immunoreactive for the regulatory peptide CGRP is
      caused by an accumulation of peptide within the cells which renders them more
      detectable, rather than by a real increase in proliferation. The incorporation of
      continuously infused 5'-bromodeoxyuridine (BrdU) into nuclei of CGRP-containing
      cells was studied by immunohistochemistry in the airway and respiratory
      epithelium of rats kept in a hypoxic (10% O2), normobaric conditions for 7 days
      and in normoxic, normobaric controls. Some CGRP-immunoreactive cells could also
      be labelled for BrdU. However, the ratio of the number of cells labelled with
      both CGRP and BrdU to the number of cells labelled with CGRP alone did not differ
      significantly between hypoxic and normoxic rats (7.1 +/- 0.7 and 6.1 +/- 1.2,
      respectively; mean +/- SEM; P = 0.49). These data strongly suggest that CGRP
      containing endocrine cells or their precursors do proliferate in adult rat lung,
      but that the proliferation is not increased significantly in hypoxia.

PMID- 1386792
TI  - Effect of reduced aortic compliance on cardiac efficiency and contractile
      function of in situ canine left ventricle.
AB  - This study tests the hypothesis that arterial vascular stiffening adversely
      influences in situ left ventricular contractile function and energetic
      efficiency. Ten reflex-blocked anesthetized dogs underwent a bypass operation in
      which a Dacron graft was sewn to the ascending aorta and connected to the
      infrarenal abdominal aorta via a plastic conduit. Flow was directed through
      either native aorta or plastic conduit by placement of vascular clamps. Arterial
      properties were measured from aortic pressure-flow data, and ventricular function
      was assessed by pressure-volume (PV) relations. Coronary sinus blood was drained
      via an extracorporeal circuit for direct measurement of myocardial O2 consumption
      (MVO2). Data at multiple steady-state preload volumes were combined to derive
      chamber function and energetics relations. Energetic efficiency was assessed by
      the inverse slope of the MVO2-PV area relation. Directing flow through plastic
      versus native aorta resulted in a 60-80% reduction in compliance but little
      change in mean resistance. Arterial pulse pressure rose from 34 to 99 mm Hg (p
      less than 0.001). Contractile function assessed by the end-systolic PV relation,
      stroke work-end-diastolic volume relation, and dP/dtmax at matched end-diastolic
      volume did not significantly change. However, MVO2 increased by 32% (p less than
      0.01) and was matched by a rise in PV area, such that the MVO2-PV area relation
      and efficiency was unaltered. The MVO2 required to sustain a given stroke volume,
      however, increased from 20% to 40%, depending on the baseline level (p less than
      0.001). Thus, whereas the contractile function and efficiency of normal hearts
      are not altered by ejection into a stiff vascular system, the energetic cost to
      the heart for maintaining adequate flow is increased. This suggests a mechanism
      whereby human vascular stiffening may yield little functional decrement at rest
      but limit reserve capacity under conditions of increased demand.

PMID- 1386794
TI  - Transcatheter management of cyanotic congenital heart defects: a review.
AB  - In this review, the role of transcatheter methods in the management of cyanotic
      congenital heart defects is discussed. In patients with interventricular right-to
      left shunting secondary to pulmonary outflow tract obstruction (most commonly
      tetralogy of Fallot), balloon dilatation may be an effective palliative procedure
      in a substantial proportion of patients, obviating the need for a palliative
      shunt. We would recommend this if the patient's size or cardiac anatomy makes
      that patient an unsuitable candidate for safe total surgical correction.
      Infundibular myectomy with atherectomy catheter in tetralogy of Fallot patients
      may become a useful adjunct in the management of these infants. Cyanotic children
      with interatrial right-to-left shunt secondary to severe valvar pulmonary
      stenosis respond to balloon pulmonary valvuloplasty in a manner similar to that
      seen with isolated pulmonary valve stenosis. In these patients, balloon
      valvuloplasty is the treatment of choice and may be corrective in most cases. In
      patients with a narrowed Blalock-Taussig shunt, balloon angioplasty may improve
      pulmonary oligemia and systemic arterial hypoxemia and may obviate the need for a
      second systemic-to-pulmonary artery shunt. Balloon angioplasty is recommended if
      the patient's cardiac defect is not amenable to surgical correction at a low risk
      either because of the size of the patient or because of the complexity of the
      cyanotic heart defect. In patients with pulmonary valve atresia, initial opening
      of the atretic pulmonary valve by either laser or surgery with subsequent balloon
      dilatation is potentially beneficial in reducing the total number of surgical
      procedures that these children are likely to require. However, further clinical
      trials are needed prior to their general use.

PMID- 1386795
TI  - Allosteric control of 6-phosphofructo-1-kinase from rat lung.
AB  - 1. The regulation of 6-phosphofructo-1-kinase (PFK) in the rat lung of normally
      fed (control), 72 hr-starved and streptozotocin-induced diabetic rats was
      investigated. 2. No significant changes in the total enzyme activities and the
      activity ratios [activity at 0.5 mM fructose 6-phosphate at pH 7.0/activity at pH
      8.0 (v0.5/V)] of rat lung were observed between the control and 72 hr-starved or
      streptozotocin-induced diabetic rats. 3. Rat lung PFK was highly stimulated by
      fructose 2,6-bisphosphate (Fru-2,6-P2) as the affinity of the enzyme for fructose
      6-phosphate was highly increased by this metabolite and the enzyme inhibition by
      ATP was released. 4. Although rat liver and mucosal PFK were found to be highly
      sensitive to stimulation by Fru-2,6-P2, lung PFK was significantly more sensitive
      to the stimulation by this metabolite than the other tissues. 5. The enzyme was
      highly inhibited by citrate and was only slightly inhibited by phosphocreatine.
      6. ADP, AMP and c-AMP were shown to be activators of lung PFK with c-AMP being
      the most effective activator. 7. As a rate limiting enzyme of glycolysis, rat
      lung PFK is highly controlled by its allosteric effectors, especially Fru-2,6-P2,
      possibly for surfactant lipid synthesis which usually requires a high rate of
      glycolysis.

PMID- 1386796
TI  - The decline of atrial natriuretic peptide (ANP) gene expression in older rats and
      the effects of ginsenoside on ANP gene expression.
AB  - 1. The levels of atrial natriuretic peptide(ANP) gene expression in rat atria at
      2-3 and 14-18 months of age and the effects of ginsenosides on r-ANP gene
      expression by determining the concentration of ANP-mRNA were investigated. The
      male and female rats were abdominally (i.p.) injected with aqueous solution of
      ginsenosides prepared from ginseng stems and leaves (G-PSL) and ginseng roots (G
      PR), 50 mg/kg body wt, once a day for 7 days. Atria total RNA was extracted by
      the cold phenol method. The ANP-mRNA contents were determined using the Northern
      blot and dot blot hybridization technique with alpha-32*P-labelled r-prepro-ANP
      cDNA probe. 2. The ANP-mRNA contents of 14-18 month rats were remarkably less
      than that of 2-3 month rats. The levels of male and female rats' atria at 14-18
      months were about 15 and 60%, the content of male and female rats at 2-3 months
      respectively. 3. G-PSL and G-PR increased the ANP-mRNA content of male rats at 14
      18 months 1- and 2-fold, respectively, whereas G-PSL and G-PR decreased the ANP
      mRNA content in male rats of age 2-3 months. 4. These results revealed that the
      ANP gene expression declined during ontogenic ageing development and ginsenosides
      possessed anti-ageing effects in the heart endocrineous function aspect.

PMID- 1386798
TI  - Myosin light chain patterns in histochemically typed single fibers of the rat
      skeletal muscle.
AB  - 1. This study was conducted to investigate the relationship between histochemical
      fiber types and myosin light chain patterns in rat single muscle fibers. 2. The
      hybrid of fast and slow light chains was observed in type I and II fibers of the
      soleus and type II fibers of the red portion of lateral head of the gastrocnemius
      muscles. 3. We also observed 7 types of light chain composition. Of the 7 types,
      5 types were explainable by assuming the coexistence of isomyosins with either
      fast or slow light chains. However, the other 2 types could not be accounted for
      without hypothesizing the presence of isomyosins with promiscuous light chain
      distribution.

PMID- 1386797
TI  - Comparison of muscle phosphofructokinase from euthermic and hibernating Jaculus
      orientalis. Purification and determination of the quaternary structure.
AB  - 1. The structural properties of skeletal muscle phosphofructokinase from
      euthermic and hibernating jerboa were compared. 2. The enzyme was purified by a
      rapid procedure; suspended in ammonium sulfate in the presence of ATP, it was
      found to be stable for three weeks. 3. A specific activity of 76 U/mg and at most
      65 U/mg was obtained for the enzyme from the euthermic and hibernating jerboa,
      respectively. 4. The molecular weight was estimated to be 320 kDa for the
      oligomer and 80 kDa for the subunit. 5. A unique alanine residue was found at the
      C-terminal end, suggesting that the enzyme is a tetramer made of four identical
      subunits. 6. The tetrameric structure of phosphofructokinase was confirmed by
      using crosslinking with disuccinimidyl esters. 7. The kinetics of formation of
      the different crosslinked species were found to be in agreement with a model of
      the tetramer corresponding to a dihedral symmetry with isologuous contacts
      between protomers. 8. The same molecular characteristics and immunochemical
      properties were found for the enzyme extracted from the euthermic and hibernating
      animals.

PMID- 1386799
TI  - Calmodulin and dynamics of interactions of cytosolic enzymes.

PMID- 1386801
TI  - The molecular physiology of citrate.

PMID- 1386800
TI  - Organization of RNA splicing in the cell nucleus.

PMID- 1386802
TI  - Interactions of glycolytic enzymes with cellular membranes.

PMID- 1386803
TI  - Interaction between the carboxyl groups of Asp127 and Asp129 in the active site
      of Escherichia coli phosphofructokinase.
AB  - The pH dependence of the enzymic properties of the phosphofructokinase from
      Escherichia coli was compared to those of two mutants in which one carboxyl group
      of the active site has been removed from either Asp127 or Asp129. All
      measurements of activity were made in the presence of allosteric activator ADP or
      GDP to eliminate any cooperative process. Asp129 is a crucial residue for the
      activity of phosphofructokinase since its conversion to Ser decreases the
      catalytic activity by 2-3 orders of magnitude in both the forward and reverse
      reactions, but the ionization of Asp129 is not directly related the pH dependence
      of phosphofructokinase activity. This pH dependence is however modified by the
      Asp129----Ser mutation, which decreases the pK of another residue, Asp127, by as
      much as pH of 1.5. The side chain of Asp127 has the catalytic role proposed
      earlier: its deprotonated form acts as a base in the forward reaction, and its
      protonated form acts as an acid in the reverse reaction. The protonated form of
      Asp127 is also required for the binding of fructose 1,6-bisphosphate. The
      electrostatic interaction between the carboxyl groups of Asp127 and Asp129 seems
      different in free phosphofructokinase to that in enzyme/substrate complexes,
      suggesting that a conformational change occurs upon substrate binding. The pH
      dependence of phosphofructokinase activity involves one other ionizable group
      with a pK of approximately 6 which does not belong to the side chains of Asp127
      or Asp129.

PMID- 1386804
TI  - Mapping of three unique Ca(2+)-binding sites in human annexin II.
AB  - Site-directed mutagenesis was employed to map and characterize Ca(2+)-binding
      sites in annexin II, a member of the annexin family of Ca(2+)- and phospholipid
      binding proteins which serves as a major cellular substrate for the tyrosine
      kinase encoded by the src oncogene. Several single amino acid substitutions were
      introduced in the human annexin II and the various mutant proteins were scored
      for their affinity towards Ca2+ in different assays. The data support our
      previous finding [Thiel, C., Weber, K. and Gerke V. (1991) J. Biol. Chem. 266,
      14,732-14,739] that a Ca(2+)-binding site is present in the third of the four
      repeat segments which comprise the 33-kDa protein core of annexin II. In addition
      to Gly206 and Thr207, which are localized in the highly conserved endonexin fold
      of the third repeat, Glu246 is involved in the formation of this site. Thus the
      architecture of this Ca(2+)-binding site in solution is very similar, if not
      identical, to that of Ca2+ sites identified recently in annexin V crystals
      [Huber, R., Schneider, M., Mayr, I., Romisch, J. and Paques, E.-P. (1990) FEBS
      Lett. 275, 15-21]. In addition to the site in repeat 3, we have mapped sites of
      presumably similar architecture in repeats 2 and 4 of annexin II. Again, an
      acidic amino acid which is located 40 residues C-terminal to the conserved
      glycine at position 4 of the endonexin fold is indispensable for high-affinity
      Ca2+ binding: Asp161 in the second and Asp321 in the fourth repeat. In contrast,
      repeat 1 does not contain an acidic amino acid at a corresponding position and
      also shows deviations from the other repeats in the sequence surrounding the
      conserved glycine. These results on annexin II together with the crystallographic
      information on annexin V reveal that annexins can differ in the position of the
      Ca2+ sites. Ca(2+)-binding sites of similar structure are present in repeats 2,
      3, and 4 of annexin II while in annexin V they occur in repeats 1, 2, and 4. We
      also synthesized an annexin II derivative with mutations in all three Ca2+ sites.
      This molecule shows a greatly reduced affinity for the divalent cation. However,
      it is still able to bind Ca2+, indicating the presence of (an) additional Ca2+
      site(s) of presumably different architecture.

PMID- 1386805
TI  - A model system of coupled activity of co-immobilized creatine kinase and myosin.
AB  - Myosin and creatine kinase were co-immobilized onto Immunodyne films to mimic the
      behaviour of creatine kinase bound to the M-line of myofilaments. The Mg-ATPase
      activity of bound myosin was studied by a coupled enzymatic assay, which detects
      Mg-ADP in the bulk solution by means of pyruvate kinase and lactate
      dehydrogenase. The competition for Mg-ADP between pyruvate kinase and creatine
      kinase either free in solution or co-immobilized with myosin was studied at
      various creatine phosphate concentrations. Bound creatine kinase competed
      efficiently when present in very low amounts, corresponding to an activity ratio
      higher than 1:20,000 between creatine kinase and pyruvate kinase and a molar
      ratio higher than 1:1000 between creatine kinase and myosin. The Mg-ADP produced
      by myosin ATPase in the vicinity of the film did not diffuse into the bulk
      solution but, in the presence of creatine phosphate, was recycled into Mg-ATP by
      the neighbouring creatine kinase. The existence of an unstirred layer near the
      surface of the film is sufficient to explain the channeling of ADP (or ATP)
      between co-immobilized myosin and creatine kinase, without direct interaction or
      'intimate coupling' between the enzymes. The problem now is to determine the
      importance of this kind of facilitated diffusion in the myofilaments in vivo.

PMID- 1386806
TI  - Differential effects of ketamine enantiomers on NMDA receptor currents in
      cultured neurons.
AB  - The effects of R- and S-ketamine on N-methyl-D-aspartate receptor-activated
      cation currents (NMDA receptor currents) of voltage-clamped cultured rat
      hippocampal neurons were investigated using the whole-cell patch-clamp technique.
      Both enantiomers exhibited a voltage- and use-dependent blockade of NMDA receptor
      currents, with the S-enantiomer being about twice as potent as the R-enantiomer.
      Calculated relative forward and backward rates suggest that conformational
      differences influence the dissociation from the binding site more than the
      association with it.

PMID- 1386808
TI  - Angioscopy: a new light on peripheral vascular disease.
AB  - Although fibre-optic imaging has been used in a number of medical specialties for
      several years, it has only recently begun to develop in the area of peripheral
      vascular disease. This review considers the historical development of angioscopy,
      its current role in peripheral vascular surgery and, finally, its potential for
      the future.

PMID- 1386807
TI  - Suspected distinct activation pathways of human lymphocytes induced by
      antilymphocyte globulin and anti-CD3 monoclonal antibody result in different
      secretion of hematopoietic colony-stimulating activities.
AB  - We evaluated the activation sequence of peripheral blood lymphocytes from healthy
      donors using different mitogens, including antilymphocyte globulin (ALG), anti
      CD3 monoclonal antibody (OKT3), and phytohemagglutinin (PHA). Blood mononuclear
      cells stimulated by ALG, OKT3 and PHA incorporated 3H-thymidine in the same way.
      When enriched T cells were tested in the presence of interleukin-1 alpha (0 to
      100 U/ml, incorporation of 3H-thymidine was greater in those cells stimulated by
      ALG than by PHA. OKT3 did not activate enriched T cells. Thymidine incorporation
      was reduced to less than 50% of maximum concentrations by the addition of 10(-7)
      mol/1,25-dihydroxyvitamin D3 (vit D3) in PHA- or OKT3-activated cells. However,
      the inhibitory effect of vit D3 was not apparent in ALG-activated cells.
      Production of granulocyte-macrophage colony-stimulating factor and interleukin-3
      by lymphocytes upon activation was consistently higher when cells were treated
      with ALG or PHA than with OKT3. Taken together, the data indicate that there
      appear to be distinct functional mechanisms between ALG- and OKT3-induced
      lymphocyte activation that lead to characteristic immunohematologic events.

PMID- 1386809
TI  - Graft replacement of post-traumatic thoracic aortic aneurysm: results without
      bypass or shunting.
AB  - From 1986 to 1991 13 cases of post-traumatic thoracic aneurysm were treated at
      our department. All patients had apparent thoracic injury at the time of trauma,
      and their mean age was 35 years. The mean time between trauma and operation was 3
      years and six patients were asymptomatic. In all patients the diagnosis was made
      by computed tomography and angiography and all post-traumatic thoracic aneurysms
      were located at the aortic isthmus. No spinal cord protection by bypass or
      shunting was used during surgery and the clamp-and-repair method with a mean
      clamping time of 38 min was used in all 13 patients. No renal or neurological
      complications were observed postoperatively and there were no hospital deaths.
      The data of 202 patients who had been operated upon for post-traumatic thoracic
      aneurysms since 1981 have been reviewed with regard to the relationship between
      spinal cord protection and the incidence of postoperative paraplegia. Different
      methods of spinal cord protection were used in 121 patients resulting in
      paraplegia rate of 1.6%. In 81 patients the clamp-and-repair method was used and
      no case of paraplegia was observed in this group.

PMID- 1386810
TI  - The acute thrombogenicity of an infection-resistant rifampicin-soaked Dacron
      graft: an experimental study in sheep.
AB  - Every effort to reduce synthetic graft infection is welcome and when designing
      antibiotic-bonded grafts it is important not to increase graft thrombogenicity.
      In order to study the acute thrombogenicity of rifampicin-soaked gelatin-sealed
      Dacron grafts compared with untreated gelatin-sealed Dacron grafts, an
      experimental carotid artery sheep model was used. Twenty sheep were anaesthetised
      and 7-cm-long 5-mm-wide externally supported gelatin-sealed knitted Dacron grafts
      were sutured end to end into each carotid artery after excising a portion of that
      vessel. Test grafts had previously been immersed for 15 min in a rifampicin
      solution (1 mg ml-1) while control grafts were immersed in physiological saline
      for 15 min. There were two groups with 10 sheep in each. In one group the blood
      flow through the grafts was unrestricted but in the second the flow was
      restricted to 25 ml min-1. Platelets from sheep labelled with 111In and sheep
      fibrinogen labelled with 125I were injected intravenously. The isotope activities
      were continuously measured proximally and distally over the grafts for 4 h. With
      unrestricted flow 4 out of 10 rifampicin-soaked grafts occluded compared with 2
      out of 10 control grafts (N.S.). Time to occlusion, thrombus weight, platelet and
      fibrinogen activity did not differ. In the restricted flow group 9 out of 10
      rifampicin-soaked grafts occluded compared with 6 out of 10 control grafts
      (N.S.). The time to occlusion did not differ. The thrombus weight in the
      rifampicin group was significantly higher compared with the control
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386811
TI  - [Age-related changes in glucocorticoid and mineralocorticoid receptors in
      lymphocytes of healthy persons and patients with hypertension].
AB  - It has been found that the number of glucocorticoid receptors in lymphocytes of
      the peripheral blood of healthy elderly subjects increases, while the number of
      mineralocorticoid receptors decreases. The mechanisms of hormone-receptor
      interactions in hypertension are activated: the number of glucocorticoid and
      mineralocorticoid binding sites grows in hypertensive patients. Still a more
      essential rise in the number of receptors is observed in mid-age hypertensive
      patients than in elderly ones.

PMID- 1386813
TI  - Proper etiquette with the disabled.

PMID- 1386812
TI  - Dental care courses for adults with disabilities.

PMID- 1386814
TI  - Now there's another ADA in your life.

PMID- 1386815
TI  - Ontogeny of leukocyte populations in the ileal Peyer's patch of sheep.
AB  - Enzyme- and immunohistochemical methods were used to characterize the leukocyte
      populations present in the ileal Peyer's patches of sheep foetuses between 68 and
      135 d of gestation and particularly in the period around 100 d of gestation, when
      active lymphopoiesis begins. A wide variety of leukocytes including IgM+, CD5+,
      CD4+, CD8+ cells, and MgATPase+ dendritic cells were present at an early stage.
      Groups of IgM+ cells were seen immediately beneath the epithelium as early as 70
      d of gestation. Conventional morphometric and computer-assisted morphometric
      techniques were used to confirm the significant expansion of these cell
      populations from 90 d of gestation. IgM+ and CD5+ cells were responsible for the
      vast majority of the increase in cell numbers. It was concluded that a diverse
      leukocyte population was present at the initiation of active lymphopoiesis in the
      ileal PP of the sheep foetus and that all members of this population were
      associated with the emergence of the dome/follicle primordia from which the B
      cell follicle develops.

PMID- 1386816
TI  - Gastroschisis: what part can the obstetrician play?
AB  - In order to assess the contribution of antenatal diagnosis to the management of
      gastroschisis, the antenatal and postnatal data from 24 cases of gastroschisis
      observed between 1974 and 1990 were re-examined. The frequency of antenatal
      diagnosis (29%), polyhydramnios (21%), atresia of the small intestine (29%),
      length of pregnancy (36.6 +/- 2 weeks of amenorrhea), proportion of cesarean
      sections (21%), birth weight (2230 +/- 430 g) and the Apgar score after 5 min
      (9.0 +/- 1.5) were comparable to findings reported elsewhere. The overall
      mortality rate for the period studied was high (41%), and was not influenced by
      any antenatal parameter or by the mode of delivery; its recent fall (P = 0.01) is
      explained by the development of therapeutic methods. These results are consistent
      with other recent studies and suggest that antenatal diagnosis does not enable an
      accurate assessment of the prognosis to be made and has no major influence on the
      mortality rate in gastroschisis.

PMID- 1386817
TI  - The response of uterine fibroids to GnRH-agonist treatment can be predicted in
      most cases after one month.
AB  - Twenty-seven patients with uterine fibroids were treated for 3 months with the
      GnRH-agonist goserelin prior to surgical myomectomy. Ovarian function was
      suppressed reliably in all patients. After three applications, 15 fibroids were
      reduced in volume by more than 50%, and one complete remission was achieved.
      Seven patients showed a decrease of 10-50% in volume. However, in 5 cases there
      was no significant reduction. Analysing the time course of the fibroid reduction,
      the response can be predicted in most cases as early as four weeks after the
      first injection. Retrospective statistical analysis showed that a 50% reduction
      in fibroid size due to GnRH treatment is preceded by a 35% reduction after 4
      weeks in 81% of cases, and after 8 weeks in all cases. Only 2 of 12 fibroids,
      which showed a smaller response (less than 50%) to GnRH therapy, were reduced by
      more than 35% after 4 and 8 weeks. In most cases it seems to be possible to
      estimate the individual response to GnRH-application after the first injection,
      so that it is possible to stop therapy in non-responding patients.

PMID- 1386818
TI  - Altered regulation of renin secretion by insulinlike growth factors and
      angiotensin II in diabetic rats.
AB  - The etiology of the low renin state in DM is not clear. To assess the role of
      certain growth and regulatory factors in this process, we studied the effects of
      insulin, IGF-I, and IGF-II on the renin-angiotensin system in normal and 8-wk STZ
      induced diabetic rats. Renin secretion was studied both in static incubations and
      by perifusion of rat renal cortical slices. In diabetic rats, both plasma renin
      activity (0.65 +/- 1.6 vs. 4.0 +/- 1.2 ng ANG I.ml-1.h-1) and tissue renin
      concentrations (27 +/- 5 vs. 51 +/- 8 ng ANG I.mg tissue-1.h-1) were reduced.
      Insulin (0.1-1.0 mu/ml) and IGF-I (10(-9) to 4 x 10(-9) M) stimulated renin
      secretion in normal tissue (control, 95 +/- 3%; insulin [0.5 mu/ml], 134 +/- 7%;
      IGF-I [4 x 10(-9) M], 149 +/- 7%). IGF-I stimulated renin secretion in
      perifusions as early as 30 min, whereas IGF-II had no effect. However, in
      diabetic renal tissue, neither insulin (0.1-1.0 mu/ml) nor IGF-I (10(-9) to 4 x
      10(-9) M) had an effect on renin. This lack of effect was overcome by adding up
      to 100-fold higher concentrations of these growth factors. ANG II (10(-10) M-10(
      8) M) had an exaggerated inhibitory effect on renin secretion in diabetic tissue.
      This study suggests that the low renin state in DM may be explained by the
      enhanced inhibitory effect of ANG II and the resistance to the secretogogue
      actions of insulin and IGF-I.

PMID- 1386820
TI  - Brain D1 dopamine receptor in alloxan-induced diabetes.
AB  - Specific binding of [3H]SCH 23390 to dopamine D1 receptors in the striatum and
      olfactory tubercle in 14-day alloxan-induced diabetic rats was investigated. The
      Scatchard analysis revealed decreased D1 receptor density in the striatum (Bmax
      values were 548 +/- 23 fmol/mg protein for the control and 466 +/- 33 fmol/mg for
      the diabetic rats). No change was observed in the olfactory tubercle (Bmax; 299
      +/- 27 fmol/mg for the control and 317 +/- 32 fmol/mg for the diabetic rats).
      Thus, specific binding of [3H]SCH 23390 to striatal and olfactory tubercle
      membranes showed region-specific changes of brain dopamine D1 receptors in
      alloxan diabetic rats.

PMID- 1386819
TI  - Tissue-specific regulation of insulin receptor mRNA levels in rats with STZ
      induced diabetes mellitus.
AB  - In rats with STZ-induced diabetes mellitus, a reduction in insulin secretion is
      associated with increased insulin binding in the liver, muscle, fat, and kidney,
      but not in the brain. To test the hypothesis that tissue-specific modulation of
      insulin receptors (IRs) in STZ-induced diabetes occurs at the level of mRNA, IR
      mRNA levels were measured in the liver, kidney, and brain of Sprague-Dawley rats
      15 days after intravenous administration of STZ (60 mg/kg body weight) and
      compared with those of control rats. Diabetic rats were either left untreated or
      given differing insulin regimens that were designed to achieve varying degrees of
      metabolic control. IR mRNA levels were measured by slot blot hybridization with a
      32P-labeled rIR probe and standardized by 28S ribosomal RNA determination.
      Hepatic IR mRNA levels were increased significantly in both untreated diabetic
      rats and in those that received low-dose (2 U/day) insulin therapy. In contrast,
      hepatic IR mRNA levels did not differ significantly from controls in those that
      received moderate doses of insulin (3-8 U/day) and were significantly less than
      controls in those that received the highest doses (6-10 U/day). Renal IR mRNA
      levels also were increased significantly in the untreated diabetic rats but not
      in those that received low- or moderate-dose insulin therapy, and were
      significantly less than controls in those that received the highest
      doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386821
TI  - Cerebral taurine transport is increased during streptozocin-induced diabetes in
      rats.
AB  - Taurine is a cerebral osmolyte whose intracellular content changes in parallel
      with plasma osmolality. We conducted experiments to assess whether cerebral
      taurine transport is modified during chronic hyperglycemia. Rats with STZ-induced
      diabetes were studied after 1 wk of sustained hyperglycemia. Cerebral taurine
      uptake in synaptosomes (metabolically active nerve terminal vesicles) was
      measured using a rapid filtration technique. The synaptosomes were isolated by
      homogenization of the brain and purification on discontinuous Ficoll gradients (n
      = 8 synaptosome preparations). Diabetic rats (n = 13) displayed a 15-25% increase
      in synaptosomal taurine uptake compared with normoglycemic control animals (n =
      12) at all time points assayed between 5 and 120 min. Thus, after a 30-min
      incubation, cerebral taurine uptake increased from a control level of 3.53 +/-
      0.23 to 4.10 +/- 0.24 mumol/mg protein (n = 10) in hyperglycemic rats, P less
      than 0.03. The magnitude of the plasma-to-brain cell taurine gradient was
      unchanged in diabetic animals. The intrasynaptosomal taurine concentration
      (approximately 2 microM) and taurine efflux from the synaptosomes were no
      different in hyperglycemic versus control rats; efflux amounted to less than 2.5%
      of the uptake value at corresponding time points. Maximal brain taurine uptake
      under both control and experimental hyperglycemic conditions required the
      presence of external Na+ and Cl-. Synaptosomal taurine transport was reduced by
      competing beta-amino acids such as beta-alanine, beta-aminoisobutyric acid, and
      hypotaurine (P less than 0.01). Addition of oubain and the anionic binding site
      inhibitors, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid and
      4,4'diisothio-cyanatostilbene-2,2'-disulfonic acid, also decreased cerebral
      taurine uptake under normoglycemic and hyperglycemic conditions (P less than
      0.01). The increased synaptosomal taurine uptake by diabetic rats was not a
      result of generalized membrane dysfunction because glycine transport was not
      elevated in hyperglycemic rats. The enhanced transport rate was attributable to a
      35 and 81% increase in the Vmax of the high- and low-affinity taurine
      transporters, respectively (P less than 0.01), without significant change in the
      Km of the carrier systems. Treatment of hyperglycemic rats (n = 5) with ultra
      long-acting insulin to normalize the serum glucose concentration restored
      synaptosomal taurine uptake to the level observed in normoglycemic controls. The
      effect of insulin was attributable to correction of hyperglycemia, because
      addition of insulin (500 mU/ml) to the in vitro assay system did not alter
      synaptosomal taurine uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1386822
TI  - [Endocrine system functioning in natives of the Russian North-East. II.
      Glucocorticoid function in the adrenal cortex of the Evenks and Chukchis].

PMID- 1386823
TI  - Thromboxane-receptor blockade increases water diuresis in cirrhotic patients with
      ascites.
AB  - This study was undertaken to investigate the role of increased renal thromboxane
      (TX) A2 production in modulating renal hemodynamics and sodium and water
      retention in cirrhotic patients with ascites. In a randomized, double-blind,
      placebo-controlled, crossover trial, 15 nonazotemic cirrhotic patients with
      ascites and elevated urinary TXB2 excretion received the thromboxane-receptor
      antagonist ONO-3708 (3 micrograms.kg-1.min-1) in a 4-hour continuous infusion.
      Administration of ONO-3708 significantly blocked TXA2 receptors; bleeding time
      showed a twofold increase (432 +/- 65 vs. 131 +/- 17 seconds; P less than 0.005),
      and platelet aggregation to U-46619 (an agonist of TXA2 receptors) was abolished
      in all patients studied. The drug induced a significant increase in free water
      clearance (3.06 +/- 0.70 vs. 1.72 +/- 0.57 mL/min; P less than 0.001) and
      diuresis (4.74 +/- 0.79 vs. 3.94 +/- 0.66 mL/min; P less than 0.05) compared with
      placebo, as well as a significant (14%) increase in renal plasma flow. The
      increases in both free water clearance and diuresis induced by ONO-3708 were
      directly related to basal urinary TXB2 excretion. These results suggest a role
      for renal TXA2 as a modulator of water handling in cirrhotic patients with
      ascites.

PMID- 1386824
TI  - Fish oil and colon cancer.

PMID- 1386826
TI  - Dental management of the heart transplant patient.

PMID- 1386827
TI  - Antidepressant medications.

PMID- 1386825
TI  - Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at
      risk for colon cancer.
AB  - The effects of 12 weeks of omega-3 fatty acid supplementation on rectal mucosal
      proliferation were assessed with [3H]thymidine autoradiography in a double-blind,
      placebo-controlled study of 20 patients with sporadic adenomatous colorectal
      polyps. In the group of 10 that received fish oil containing eicosapentaenoic
      acid (4.1 g/day) and docosahexaenoic acid (3.6 g/day), the mean percentage of
      replicative "S"-phase cells in the upper part of colonic crypts (considered a
      reliable marker of colon cancer risk) significantly dropped from the baseline
      level after only 2 weeks of treatment and remained lower throughout the study
      period; no change in upper-crypt labeling was observed in the 10 placebo
      patients. Rectal mucosal eicosapentaenoic acid content increased in fish oil
      patients, whereas arachidonic acid levels decreased. The fish oil-induced kinetic
      changes represent contraction of the proliferative compartment to the levels of a
      low-risk population and may be related to omega-3 fatty acid effects on the
      arachidonic prostaglandin pathway. In this short-term trial, fish oil appeared to
      exert a rapid effect that may protect high-risk subjects from colon cancer.

PMID- 1386828
TI  - Continuing education and patients with HIV: attitudes, perceived risk, and
      willingness to treat.

PMID- 1386829
TI  - Severely disabled elderly persons with financially catastrophic health care
      expenses: sources and determinants.
AB  - This article describes the sources of financially catastrophic health care
      expenses among disabled elderly persons. Using a cost-to-income approach and data
      from the 1981-1982 Channeling Demonstration project, we examined the types of
      health care costs (hospital, physician and ancillary care, nursing home, and
      prescription medicine) that contributed to overall expenses. For the Channeling
      sample, out-of-pocket expenses for prescription medicines and for nursing home
      care were the principle source of catastrophic expenses.

PMID- 1386830
TI  - A 28-day feeding study with methyl isoeugenol in rats.
AB  - Methyl isoeugenol was administered in rodent diet for a minimum of 28 consecutive
      days to groups of 16 male and 16 female rats (Sprague-Dawley strain) at levels of
      approximately 30, 100 and 300 mg/kg body weight/day. A further group of 16 male
      and 16 female rats was given the rodent diet as a control. The administration of
      methyl isoeugenol in the diet did not adversely affect the growth or general
      health of the animals or their food intakes. Although high dose animals of both
      sexes had increased lymphocyte and total white blood cell counts, these are not
      considered, in isolation, to be an adverse effect of treatment. None of the minor
      variations observed in the serum chemical analyses or urine analyses is
      considered to be indicative of a treatment-related toxic effect. An increase in
      liver weight, adjusted for body weight, was seen in male and female rats
      receiving 300 mg methyl isoeugenol/kg body weight. Few histopathological
      abnormalities were observed. Although the incidence of kidney and Harderian gland
      lesions was higher for high dose animals compared with the controls, the lesions
      are of a type that occurs spontaneously and are thus not considered to be
      attributable to treatment with methyl isoeugenol. While the increased liver
      weight and white blood cell counts of rats given 300 mg methyl isoeugenol/kg body
      weight may represent effects of treatment, it is not considered that there is any
      reason to regard these as adverse effects.

PMID- 1386831
TI  - [Fc gamma receptors: structure, function, and clinical significance].
AB  - Fc gamma receptors are a group of three different receptors with several
      subtypes. They are widely distributed on many cells of the immune system and
      contribute to the pathogenesis of immune complex- and autoantibody-mediated
      diseases such as vasculitis, rheumatoid arthritis, idiopathic thrombocytopenic
      purpura or autoimmune neutropenia. This review focuses on the structure,
      distribution and function in Fc gamma receptors and their subtypes.

PMID- 1386832
TI  - [The GPI-anchored Fc gamma receptor III in the activation of granulocytes].
AB  - PMN express primary two Fc gamma receptors for IgG immune complexes. Fc gamma RII
      is a transmembraneous molecule in contrast to Fc gamma RIII on PMN which is GPI
      linked. In spite of the different membrane linkage both Fc gamma R use calcium as
      an intracellular signal. Cross-linking of Fc gamma RIII is more effective for
      induction of H2O2 production than Fc gamma RII. Monoclonal IgG1x cryoglobulin
      complexes activate PMN via Fc gamma RIII as shown by calcium mobilization and
      H2O2 production.

PMID- 1386833
TI  - Specific down-regulation of allograft reactivity at the cellular level: graft
      cells and responder T cells.
AB  - Local immune reactivity in an allograft is largely determined by (1) the
      immunogenicity of the grafted cells and (2) the presence of recipient
      allospecific T lymphocytes and, much more importantly, their capacity to react
      and initiate damage to the graft. Ad (1): It is still widely believed that
      allograft immunogenicity is sufficiently described by the cell surface expression
      of transplantation antigens, in particular MHC class I and II molecules. In
      extension of earlier, more complex models it will be demonstrated that
      transfected subclones of a macrophage cell line show unaltered, strong MHC
      expression but have become non-immunogenic and, most importantly, have acquired
      the capacity to render mature naive T cells anergic in a specific fashion. Ad
      (2): Starting from the above and from other observations, we have found in human
      organ graft recipients that cytotoxic T lymphocyte (CTL) frequencies may be
      specifically down-regulated but may regain their reactivity after cultivation
      under ex vivo conditions. In keeping with the latter we can now show
      quantitatively the variable presence and the functional potential of cell
      released (soluble) human MHC (HLA class I) molecules: they are able to
      specifically inhibit human CTL reactivity in a dose-dependent fashion. Taken
      together, it may be concluded that studies at the cellular level, in particular
      the level of human cells, will increasingly help us to better understand and
      manipulate the immunological interplay between the local graft cell and its most
      important antagonist, the T lymphocyte.

PMID- 1386834
TI  - Identification of a 64-kDa protein phosphorylated with glucose in human
      polymorphonuclear leukocytes in a cell-free system.
AB  - We previously reported that a 64-kDa protein (p64) in human polymorphonuclear
      leukocytes (PMN) was phosphorylated with [gamma-32P]ATP under a micromolar
      concentration of glucose in a cell-free system. The present paper presents the
      results of analysis of phosphorylation reaction and the identification of
      phosphoprotein. The findings that p64 was also phosphorylated with glucose-6
      [32P]phosphate and that phosphorylation was inhibited with mannoheptulose
      suggested that the reaction was mediated by hexokinase. In fact, it was found
      that [32P]phosphate in glucose-6-[32P]phosphate was incorporated into either p64
      or rabbit muscle phosphoglucomutase and that glucose-6-phosphate formation from
      glucose and ATP was detected in over 100-kDa fraction of PMN cytosol. These
      results showed that p64 was phosphoglucomutase in PMN and that phosphate
      incorporation into p64 was a conversion of a phosphate group in glucose-6
      phosphate produced by hexokinase. It was further demonstrated by analysis of two
      dimensional electrophoresis that p64 phosphorylated with glucose induction was
      different from another 64-kDa protein phosphorylated by stimulation with formyl
      methionyl-leucyl-phenylalanine in vivo.

PMID- 1386835
TI  - The amplifier role of T cells in the human in vitro B cell response to type 4
      pneumococcal polysaccharide.
AB  - The human B cell response to T cell independent type 2 antigens is regulated by
      thymus-derived lymphocytes. We analyzed the role of T cells in the in vitro
      antibody response to type 4 pneumococcal polysaccharide (PS4). We here show that
      the amplifying effect of T cells, which has previously been shown to be
      radioresistant and confined to T cell preparations enriched for CD4+ cells, is
      MHC non-restricted as demonstrated in cultures carried out in the presence of
      allogeneic T cells. Also, T cell clones derived from non-related donors are able
      to enhance the B cell response to PS4. All TCR alpha beta +, CD 4+ T cell clones,
      but none of the TCR alpha beta +, CD 8+ T cell clones tested, enhanced the B cell
      response to PS4. Furthermore, 3 out of 6 TCR gamma delta+ T cell clones were
      capable of enhancing the anti-PS4 B cell response. Experiments using recombinant
      lymphokines and glutaraldehyde-fixed T cells indicated that both lymphokines and
      T-B cell interactions are required for an optimal antibody response to PS4.

PMID- 1386837
TI  - Emergency tips.

PMID- 1386836
TI  - Increased phospholipase A2 activity in peritoneal leukocytes in rat experimental
      colitis.
AB  - Activated leukocytes in the peritoneal cavity have been shown to release
      phospholipase A2(PLA2) activity and increased production of eicosanoids. It is
      not known whether a similar phenomenon occurs in inflammatory bowel diseases. We
      measured PLA2 activity in the peritoneal leukocytes and eicosanoid content in the
      peritoneal cavity of rats with experimental colitis induced by
      dinitrochlorobenzene, immune complex-mediated colitis, and acetic acid-induced
      colitis. In all models of colitis, proteins in the peritoneal cavity were
      increased by 60-260% above control, leukocyte number was elevated by 3- to 10
      fold, the PLA2 activity by 4- to 32-fold, and anti-PLA2 activity was absent.
      Eicosanoid concentrations were 3- to 4-fold higher than controls. In vitro
      studies confirmed that the peritoneal leukocytes were the source of PLA2.
      Treatment of rats with dexamethasone and leukocytes in vitro reduced PLA2
      significantly, but they were well above control rats without colitis. However,
      dexamethasone did not improve the histology. These studies suggest that
      peritoneal leukocytes may serve as an additional source of inflammatory
      mediators, which may further enhance the inflammatory response in the rat colon.

PMID- 1386838
TI  - The Th1/Th2-like switch in syphilitic infection: is it detrimental?
AB  - Organisms that cause chronic diseases have evolved mechanisms to evade those
      immune defenses that resolve the acute stage of infection (10, 12-14, 21, 22, 32,
      35, 37, 38, 40, 42, 45-49, 53). Much is to be learned by specifically identifying
      the mechanisms underlying these evasive strategies. Important new insights will
      emerge in terms of immunoregulatory pathways. This in turn will facilitate
      vaccine development. A good example is leishmania infection. The acute stage of
      this disease is resolved by DTH-macrophage activation. Leishmanial components
      preferentially activate Th2 lymphocytes. As a consequence, Th1 effects are
      minimized and infection is exacerbated leading to chronicity (10, 14, 32). To
      overcome this negative tendency, leishmanial vaccines are administered in
      combination with exogenous gamma interferon (42). This selects for Th1
      predominance and generates protective immunity. Syphilis exhibits many parallels
      to the other nine chronic diseases mentioned above. Similarities include an acute
      localized stage that readily heals, early clearance via DTH-macrophage
      activation, transient concomitant immunity during acute infection, development of
      macrophage suppression through PGE2 down-regulation, beneficial effects of
      exogenous gamma interferon, and elements of autoimmunity. Some of the
      complexities of immunoregulation during treponemal infection have just begun to
      be unraveled. It will be important to develop further insight into the Th1/Th2
      switch especially as it relates to chronicity. Macrophages seem to be intimately
      involved in the mechanics of this switch, and their specific role needs further
      clarification. Whatever is learned about syphilis, as well as other chronic
      infections will contribute to a better understanding of the generalized pathways
      of immunoregulation.

PMID- 1386839
TI  - Fibronectin-binding protein of Streptococcus pyogenes: sequence of the binding
      domain involved in adherence of streptococci to epithelial cells.
AB  - The sequence of the fibronectin-binding domain of the fibronectin-binding protein
      of Streptococcus pyogenes (Sfb protein) was determined, and its role in
      streptococcal adherence was investigated by use of an Sfb fusion protein in
      adherence studies. A 1-kb DNA fragment coding for the binding domain of Sfb
      protein was cloned into the expression vector pEX31 to produce an Sfb fusion
      protein consisting of the N-terminal part of MS2 polymerase and a C-terminal
      fragment of the streptococcal protein. Induction of the vector promoter resulted
      in hyperexpression of fibronectin-binding fusion protein in the cytoplasm of the
      recombinant Escherichia coli cells. Sequence determination of the cloned 1-kb
      fragment revealed an in-frame reading frame for a 268-amino-acid peptide composed
      of a 37-amino-acid sequence which is completely repeated three times and
      incompletely repeated a fourth time. Cloning of one repeat into pEX31 resulted in
      expression of small fusion peptides that show fibronectin-binding activity,
      indicating that one repeat contains at least one binding domain. Each repeat
      exhibits two charged domains and shows high homology with the 38-amino-acid D3
      repeat of the fibronectin-binding protein of Staphylococcus aureus. Sequence
      comparison with other streptococcal ligand-binding surface proteins, including M
      protein, failed to reveal significant homology, which suggests that Sfb protein
      represents a novel type of functional protein in S. pyogenes. The Sfb fusion
      protein isolated from the cytoplasm of recombinant cells was purified by fast
      protein liquid chromatography. It showed a strong competitive inhibition of
      fibronectin binding to S. pyogenes and of the adherence of bacteria to cultured
      epithelial cells. In contrast, purified streptococcal lipoteichoic acid showed
      only a weak inhibition of fibronectin binding and streptococcal adherence. These
      results demonstrate that Sfb protein is directly involved in the fibronectin
      mediated adherence of S. pyogenes to epithelial cells.

PMID- 1386841
TI  - Effects of light exposure on the uptake of photofrin II in tumors and normal
      tissues.
AB  - DBA mice bearing CaD2 mammary carcinomas were used to determine the effect of
      giving small doses of light to the tumor area 1.5 hr after injecting Photofrin II
      (PII). The smallest light dose applied (12.5 J/cm2) had no effect on the uptake
      of PII in the tumor and its surrounding tissues, as measured 24 hr after the i.p.
      injection. However, several higher light doses increased the uptake of PII in the
      tumor significantly, the uptake in skin slightly, while the uptake in muscle
      tissue was decreased rather than increased. Thus, the PII concentration ratio
      between the tumor and the surrounding normal tissues was significantly improved.
      The rates of clearance of PII from irradiated tissues and non-irradiated tissues
      were not significantly different. Most likely, the present observations are due
      to transient pH lowering in the tumor resulting from vascular damage.

PMID- 1386840
TI  - Evidence for actinlike proteins in an M protein-negative strain of Streptococcus
      pyogenes.
AB  - Antigens shared between Streptococcus pyogenes and heart tissue may play an
      important role in autoimmune cardiac injury associated with acute rheumatic
      fever. Antiheart/antistreptococcal antibodies found in the disease react with
      antigens of S. pyogenes, including M protein and a 60-kDa antigen distinct from M
      protein. Heart antigens recognized by these cross-reactive antistreptococcal
      antibodies include myosin and actin. To investigate the presence of a
      streptococcal actin, established protocols for the polymerization and isolation
      of eukaryotic actin were used to extract and concentrate actinlike proteins from
      M- streptococcal cells. The polymerized bacterial actin from the streptococcal
      extract was probed in immunoblots with an antiactin monoclonal antibody. Two
      proteins of about 60 kDa in the polymerized bacterial actin reacted with the
      antiactin antibody. Proteins in the polymerized bacterial actin extract of about
      43 and 60 kDa behaved like eukaryotic actin by binding to myosin and DNase I
      affinity columns. Filaments were demonstrated by electron microscopy in the
      polymerized bacterial actinlike extract, which also enhanced the ATPase activity
      of eukaryotic myosin. The data suggest that proteins resembling actin are present
      in S. pyogenes.

PMID- 1386842
TI  - Menogaril in the treatment of malignant mesothelioma: a phase II study.
AB  - Menogaril is a new semisynthetic anthracycline agent derived from the antitumor
      antibiotic Nogalomycin. Compared to doxorubicin it has similar or improved
      activity in anti-tumor cell line screening; human tumor cloning assays suggest
      modest anti-tumor activity as well. Menogaril is much less cardiotoxic than
      doxorubicin. We performed a phase II trial of this agent in 22 patients with
      advanced malignant mesothelioma. At a dose of 200 mg/m2 iv every 4 weeks (160
      mg/m2 in previously radiated patients) only 1 of 22 (5%) evaluable patients had a
      partial remission lasting 4 months. (95% confidence limits 0.1-23%). The major
      toxic effects included pain at the site of infusion and granulocytopenia. While
      well tolerated, Menogaril has minimal activity in malignant mesothelioma. We do
      not plan further studies with Menogaril in this disease.

PMID- 1386843
TI  - Toremifene and its metabolites enhance doxorubicin accumulation in estrogen
      receptor negative multidrug resistant human breast cancer cells.
AB  - The enhanced accumulation of doxorubicin by agents known to reverse multidrug
      resistance provides a good functional test for evaluating modulating activity. In
      the present study, the non-steroidal triphenylethylene toremifene selectively
      increased doxorubicin accumulation in multidrug resistant estrogen receptor
      negative MDA A-1 human breast cells compared to the MDA 231 wild type cells. MDA
      A-1 cells were noted to be 1,000 fold resistant to doxorubicin (IC 50 = less than
      0.1 microgram/ml MDA 231; IC 50 = 100 micrograms/ml MDA A-1). Total accumulation
      of doxorubicin, expressed as area under the time concentration curve (AUC), was
      increased significantly in doxorubicin resistant cells (156% increase) versus
      wild type MDA 231 cells (6% increase). Correction of the accumulation defect to
      doxorubicin in drug resistant cells required a 18-20 hour pre-incubation with
      toremifene. The effects of toremifene on cell cycle in MDA A-1 cells was analyzed
      by flow cytometric techniques. Toremifene had a dose response relationship in
      blocking cells in G0-G1 reducing the number of cells entering S phase of the cell
      cycle. This effect was maximal at concentrations which increased the accumulation
      of doxorubicin in MDA A-1 cells. Several metabolites of toremifene were also
      noted to increase doxorubicin accumulation in MDA A-1 doxorubicin resistant
      cells. Tore XVIII (deaminocarboxytoremifene), Tore IV (4-hydroxy-N
      desmethyltoremifene) and N-desmethyltoremifene all increased the accumulation of
      doxorubicin significantly (114%, 128% and 42% respectively). Finally, we show
      evidence that toremifene and its active metabolites are present in high
      concentrations in human plasma following a single 200 mg oral dose.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1386844
TI  - Early experiences of laparoscopic cholecystectomy in five Irish hospitals. Irish
      Laparoscopic Group.
AB  - There are many concerns about the widespread introduction of laparoscopic
      cholecystectomy. The initial experience of five hospitals in introducing
      laparoscopic cholecystectomy was reviewed. Three hundred and eight patients were
      operated upon, and the operations were completed laparoscopically in 279 (91
      percent). One patient sustained a diathermy injury to the right hepatic duct.
      There was no mortality and the overall morbidity was 10 percent. Mean
      postoperative stay was 3.6 days. The participating surgeons considered training
      workshops to be desirable and felt that trainees should be supervised for at
      least ten cases. Laparoscopic cholecystectomy can be safely introduced and
      performed, and it should be considered in all patients undergoing
      cholecystectomy.

PMID- 1386845
TI  - Severe hypercalcaemia four months after acute oliguric renal failure--successful
      treatment with intravenous clodronate.
AB  - A 33 year old man developed acute oliguric failure lasting 66 days, eight days
      after admission with multiple gun shot wounds. On day 99 after admission, serum
      calcium was elevated mildly at 2.54 mmol/l (normal range 2.1-2.5 mmol/l). Serum
      parathormone was undetectable. He was discharged soon afterwards. He presented
      again on day 164 with nausea, vomiting and blurred vision. Fundoscopy revealed an
      ischaemic retinopathy and extensive keratopathy. Serum calcium was 3.48 mmol/l
      and serum creatinine 262 umol/l (normal range 40-110 umol/l). Repeat parathormone
      was undetectable and there was no evidence of myeloma, sarcoidosis or malignancy.
      Following treatment with intravenous saline and frusemide, serum calcium fell to
      a nadir of 3.05 mmol/l. On day 168 an infusion of sodium clodronate 300 mg was
      given. Twenty-four hours later serum calcium was 2.65 mmol/l and 48 hours later
      calcium was 2.26 mmol/l. Normocalcaemia was maintained for 17 days and severe
      hypercalcaemia never recurred. This is the first report in which biphosphonates
      have been successfully used to treat hypercalcaemia following acute renal failure
      thus obviating the need for further dialysis.

PMID- 1386846
TI  - The management of choledocholithiasis during laparoscopic cholecystectomy by
      sphincter dilatation--initial experience in ten cases.
AB  - The intra-operative management of associated common bile duct calculus during
      laparoscopic cholecystectomy in ten patients is outlined. The techniques employed
      to remove these calculi are described. The role of such techniques in the
      management of common bile duct stone is discussed.

PMID- 1386847
TI  - An anatomical study of a new method for enlargement of narrowed aortic annulus:
      intra-arterial aorto-infundibuloplasty.
AB  - A new procedure "intraarterial aorto-infundibuloplasty" for the narrowed aortic
      annulus is described. Aortic valve replacement is performed through an aorto
      pulmonary and infundibular septal incision which is eventually enlarged by a
      single patch, i.e., a two-dimensional patch instead of a three-dimensional patch
      as in Konno's procedure. An anatomical study showed that a prosthetic valve three
      sizes larger than the natural annular diameter could be implanted and the natural
      annular diameter was increased by as much as 42%.

PMID- 1386849
TI  - Three-headed outer arm dynein from Chlamydomonas that can functionally combine
      with outer-arm-missing axonemes.
AB  - A procedure was developed for isolating Chlamydomonas outer-arm dynein that can
      functionally combine with the axoneme of an outer-arm-missing mutant, oda1.
      Previous studies showed that the outer-arm dynein of this organism, containing
      three heavy chains (alpha, beta, gamma), dissociates upon extraction with a high
      salt-concentration buffer solution into an 18-S particle containing the alpha and
      beta heavy chains and a 12-S particle containing the gamma heavy chain. It was
      found, however, that the three heavy chains did not dissociate if the high-salt
      extract was centrifuged in the presence of Mg2+; the three chains constituted a
      single species (23-S dynein) sedimenting at about 23 S and displayed a three
      headed bouquet configuration in electron micrographs. Furthermore, the 23-S
      dynein had the activity to bind to the axonemes of oda1 and increase the
      reactivated motility of detergent-extracted cell models; its addition increased
      the beat frequency from 28 Hz to 53 Hz, a frequency comparable to that of wild
      type axoneme. The 18-S and 12-S dyneins, on the other hand, were unable to
      increase the motility of oda1 axonemes even when added together. The new protocol
      thus enables purification of outer-arm dynein that retains its functional
      activity. It will provide a useful experimental system with which to study the
      mechanism of outer-arm function.

PMID- 1386848
TI  - Serotonergic medications for sexual obsessions, sexual addictions, and
      paraphilias.
AB  - BACKGROUND: Paraphilias and related disorders have recently been thought of as
      sexual addictions. However, it has also been argued that these disorders are
      sexual compulsions. The question arises as to whether these disorders and
      obsessive compulsive disorder respond in the same way to pharmacotherapy. METHOD:
      We retrospectively reviewed outcome in 13 patients who presented with sexual
      symptoms and were treated with serotonin reuptake blockers. Symptoms were divided
      into paraphilias, nonparaphilic sexual addictions, and sexual obsessions.
      RESULTS: Paraphilias had the least improvement, while sexual obsessions had the
      best response to medication. CONCLUSION: Paraphilias and related disorders may be
      less responsive than sexual obsessions or compulsions to serotonin reuptake
      blockers. Perhaps paraphilias and related disorders are on the impulsive rather
      than the compulsive end of the spectrum of obsessive compulsive disorders.
      Controlled trials are, however, necessary to replicate these preliminary
      findings.

PMID- 1386850
TI  - Role of 17-kDa essential light chain isoforms of aorta smooth muscle myosin.
AB  - Aorta smooth muscle myosin contains two kinds of 17-kDa essential light chain,
      LC17nm (nonmuscle-type) and LC17gi (gizzard-type) [Hasegawa, Y., Ueda, Y.,
      Watanabe, M., & Morita, F. (1992) J. Biochem. 111, 798-803]. The LC17 isoforms
      were released from porcine aorta myosin by incubation at 46 degrees C. The rate
      of release was 1.5 to 2 times higher with LC17gi than with LC17nm. Aorta myosins
      containing the two LC17 isoforms in various ratios could be reconstituted. The
      actin-activated ATPase activity was measured as a function of LC17nm content. The
      Vm value was lower with myosin which contained more LC17nm. The apparent
      dissociation constant for F-actin, Km, was 20-fold less with myosin which
      contained 81% LC17nm than myosin which contained 23% LC17nm. A similar difference
      in the dissociation constants of myosin for F-actin was observed in the presence
      of adenylyl imidodiphosphate. The role of LC17nm appears to be to make aorta
      myosin suitable for maintaining the muscle tension with a low expenditure of
      energy. The isoform-dependent difference in the F-actin-binding affinities of
      myosin seems partly due to the difference in the affinities of LC17 isoforms
      themselves for F-actin. We found that the isolated LC17nm itself could bind with
      F-actin with a dissociation constant of 64 microM, but LC17gi could not.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1386851
TI  - Stable and slow-turning-over microtubules characterize the processes of motile
      epithelial cells treated with scatter factor.
AB  - The turnover of microtubules was studied in the processes of PtK2 cells, after
      treatment with the cytokine scatter factor (SF), using micro-injected biotin
      tubulin as a reporter of new microtubule growth. Cells treated with SF became
      dispersed and fibroblast-like in morphology, showing one or more elongated
      processes. These processes contained bundles of microtubules, a significant
      proportion of which did not turn over during incubation times of up to an hour.
      Short broken pieces of microtubule were frequently found in all parts of the
      cell, particularly after longer incubation times, suggesting that more-stable
      microtubules were cut into pieces, which were subsequently degraded. From about
      half an hour after injection small tangles of stable microtubules were found.
      Some of these were clearly within the cell bodies. Others were usually larger in
      size and seemingly located outside the injected cells. These were considered to
      have formed part of small 'feet' presumed to be broken off during the retraction
      of trailing processes. The microtubules within the processes were resistant to
      the effects of both microtubule-depolymerizing drugs and cold under conditions
      where the processes were maintained. When these microtubules disappeared as the
      result of longer drug treatment the processes were also lost although, rarely,
      short processes lacking microtubules were found. It is concluded that the stable
      microtubules have a major role in process maintenance, although one that is
      indirect rather than a structural relationship.

PMID- 1386852
TI  - Cyclin A-cdc2 kinase does not trigger but delays cyclin degradation in interphase
      extracts of amphibian eggs.
AB  - Purified cyclin B-cdc2 kinase has been shown previously to trigger cyclin
      degradation in interphase frog extracts by initiating a cascade of reactions that
      includes cyclin ubiquitinylation and ends with proteolysis. However, cyclin A
      cdc2 kinase was not assayed in these early experiments. Here we have shown that
      full-length recombinant human cyclin A failed to induce cyclin degradation when
      it was added to frog extracts free of cyclin B, although it formed an active
      kinase complex with Xenopus cdc2. A highly purified kinase complex containing a
      truncated human cyclin A and starfish cdc2 also failed to switch on the cyclin
      degradation pathway. In contrast, both recombinant cyclin B and highly purified
      cyclin B-cdc2 kinase readily triggered degradation of both cyclins B and A in
      frog extracts. Whilst free cyclin A had no inhibitory effect, cyclin A-cdc2
      kinase delayed degradation of both cyclins A and B induced by cyclin B-cdc2
      kinase. The finding that cyclin A-cdc2 kinase cannot turn on, and even delays,
      cyclin destruction may be essential to prevent premature inactivation of MPF
      (maturation-promoting factor) before complete condensation of chromosomes and
      formation of the metaphase spindle.

PMID- 1386853
TI  - Immunofluorescence study of actin, acrosin, dynein, tubulin and hyaluronidase and
      their impact on in-vitro fertilization.
AB  - Using polyclonal antibodies, the distribution of actin, acrosin, dynein, tubulin
      and hyaluronidase has been examined by indirect immunofluorescence in sperm
      preparations from fertile donors and in-vitro fertilization (IVF) patients. After
      recording sperm parameters in native semen, spermatozoa were washed free of
      seminal plasma using either the swim-up or the Percoll filtration technique.
      Prior to insemination, aliquots of the washed sperm suspensions were prepared for
      antibody staining. Spermatozoa from fertile donors were analysed in order to
      establish the specific fluorescence patterns of each antibody and the threshold
      scores of normality. Immunofluorescence scores obtained from IVF patients were
      then analysed with respect to IVF outcome. For each tested protein, the number of
      normal samples were significantly lower in the group which did not fertilize and
      fertilization rates were significantly reduced when any of the tested proteins
      were scored as pathological. Normal fluorescence scores were correlated with
      morphology, motility, velocity and to a lesser extent with sperm concentration in
      native semen. On the basis of receiver-operating characteristic curves,
      likelihood ratios and Cohen's kappa values, the presence of acrosin and tubulin
      yields the most useful information on sperm functional and structural status and
      on its fertilizing ability.

PMID- 1386854
TI  - Distribution of plasminogen and plasmin in fractions of bovine milk.
AB  - The relative amounts of immunoreactive plasminogen and active plasmin in
      different fractions of bovine milk were examined. Raw milk was centrifuged to
      separate skim, cream, and a somatic cell pellet. Skim milk was centrifuged to
      separate milk serum and casein micelles. Milk fat globule membranes were isolated
      from the cream fraction of bovine milk. Proteins from somatic cells were isolated
      following sonication of the cells. Western blot analysis showed the presence of
      several forms of plasminogen in bovine milk. The predominant forms of plasminogen
      identified following electrophoresis under nonreducing conditions were proteins
      with approximate molecular weights of 88,000, 152,000, and 160,000. The
      predominant forms of plasminogen identified after electrophoresis under reducing
      conditions were two proteins with approximate molecular weights of 88,000 and
      50,000. The highest amount (82% of the total plasminogen), as determined by an
      ELISA, was associated with the casein fraction. Lower plasminogen concentrations
      were associated with the serum, cream fractions, and milk fat globule membranes.
      The SDS-PAGE of the cream and milk fat globule membranes indicated that some
      casein was present in both fractions. Thus, the low plasminogen concentrations in
      these fractions may be associated with the caseins there. No immunoreactive
      plasminogen was present in the somatic cells. Active plasmin was present in the
      same milk fractions in which plasminogen was detected: casein, serum, and cream.

PMID- 1386855
TI  - Identification of a receptor on the vitelline membrane of bovine oocytes that
      recognizes bovine immunoglobulin G.
AB  - In order to investigate whether Ig molecules affect bovine fertility, bovine
      follicular oocytes were tested for an oolemmal receptor that recognized IgG. The
      zona pellucida was removed from 296 oocytes. The zona-free oocytes were then
      incubated with purified bovine IgG. its Fc fragment, or its Fab fragment. They
      were subsequently washed and incubated with the appropriate rabbit antibovine IgG
      (whole IgG-specific, Fc-specific, or Fab-specific), which was covalently attached
      to polyacrylamide beads (immunobeads). Bead attachment was scored using light
      microscopy. Bovine IgG and bovine IgG-Fc bound to the oocytes, whereas the IgG
      Fab exhibited negligible binding. The data indicate that a bovine oolemmal
      receptor exists that binds IgG by recognizing the molecule in the region of the
      Fc-Fab junction. Thus, the binding of IgG or other Ig molecules to bovine oocytes
      may play a role in sperm and egg interaction.

PMID- 1386856
TI  - Sociotropy and autonomy: relationship to antidepressant drug treatment response
      and endogenous-nonendogenous dichotomy.
AB  - This study evaluated the relationship of sociotropic and autonomous personality
      traits with response to pharmacotherapy for 217 depressed outpatients using the
      Sociotropy-Autonomy Scale. Sociotropy was related to nonendogenous depression,
      whereas autonomy was related to endogenous depression. Subjects who had high
      autonomous-low sociotropic traits showed greater response to antidepressants (and
      greater drug-placebo differences) than those who had high sociotropic-low
      autonomous traits (who showed no drug-placebo differences). Hierarchical multiple
      regression analysis showed that the sociotropy-autonomy, but not the endogenous
      nonendogenous, distinction was a predictor of drug treatment response. The
      combination of endogeneity and autonomy predicted response to placebo. If
      replicated, these findings may enable better matching of patient traits to
      various treatment modalities for depression.

PMID- 1386857
TI  - Ipratropium bromide aqueous nasal spray for patients with perennial allergic
      rhinitis: a study of its effect on their symptoms, quality of life, and nasal
      cytology.
AB  - Ipratropium bromide is an anticholinergic agent with topical activity that has
      been studied as a freon-propelled aerosol spray for therapy of nonallergic
      rhinitis. This is the first report of its use both as an aqueous nasal spray and
      in perennial allergic rhinitis. In this study 123 patients who had symptoms of
      perennial allergic rhinitis were randomized to receive ipratropium bromide 21
      micrograms or 42 micrograms or placebo, one spray per nostril three times a day
      for 4 weeks. Patients maintained daily diaries of duration and severity of nasal
      symptoms and were evaluated weekly. Mean duration and severity of rhinorrhea was
      decreased in both ipratropium bromide treatment groups by comparison with
      placebo, with consistently greatest improvement in the group treated with
      ipratropium bromide 42 micrograms per nostril three times a day. No statistically
      significant differences occurred among treatment groups in duration or severity
      of postnasal drip, congestion, or sneezing. Seventy percent of patients treated
      with 42 micrograms of ipratropium bromide thought it had good or excellent effect
      on rhinorrhea (p less than 0.05 vs placebo); significantly more patients thought
      that it had improved the quality of life (p = 0.02). No changes occurred in nasal
      cytology, and no significant local or systemic adverse events occurred. These
      data indicate that ipratropium bromide significantly decreases the rhinorrhea of
      perennial allergic rhinitis.

PMID- 1386858
TI  - Hemodynamic and sympathetic responses to human atrial natriuretic peptide
      infusion in patients with cirrhosis.
AB  - To determine the potential usefulness of atrial natriuretic peptide (ANP) in
      patients with cirrhosis, we examined the effects of the infusion of a low dose of
      alpha-human ANP (alpha hANP, 25 ng.kg-1.min-1 for 30 min) on renal, splanchnic,
      systemic hemodynamics and sympathetic outflow in eight patients. Pulmonary
      arterial plasma ANP concentrations increased from 59 +/- 9 to 328 +/- 41 pg/ml
      (mean +/- S.E., p less than 0.05). Mean values of glomerular filtration rate and
      renal plasma flow were not significantly changed. Individual renal plasma flow
      responses differed from one patient to another. Renal plasma flow increased in
      two patients, decreased in three and did not change in the other patients. Renal
      plasma flow changes were correlated with basal renal plasma flow values (r = 
      0.938, p less than 0.05) but not with arterial pressure changes or renal vein
      plasma norepinephrine concentration changes. Azygos blood flow increased from
      0.43 +/- 0.10 to 0.63 +/- 0.13 l/min (p less than 0.05) and the hepatic-venous
      pressure gradient decreased from 19.9 +/- 1.5 to 17.5 +/- 2.9 mmHg in post
      infusion (p less than 0.05). Mean arterial pressure decreased significantly by
      18% and cardiac output by 12%. Systemic vascular resistance and pulmonary
      arterial plasma norepinephrine concentrations were not significantly modified.
      Thus, in patients with cirrhosis, alpha hANP appears to have a direct
      vasodilating action on renal arterioles when basal renal vascular tone is high.
      In addition, although alpha hANP might exert a portal hypotensive action, alpha
      hANP induced arterial hypotension as a result of both low cardiac output and a
      lack of increased sympathetic vascular tone. The arterial hypotensive action may,
      thus, limit the therapeutic use of low doses of alpha hANP in cirrhotic patients.

PMID- 1386859
TI  - Mice deprived of exogenous antigenic stimulation develop a normal repertoire of
      functional T cells.
AB  - The development of T cells and the selection of the TCR repertoire in the absence
      of exogenous antigenic stimulation were investigated. For this purpose germfree
      BALB/c mice fed an ultrafiltered solution of chemically defined low m.w.
      nutrients (GF-CD) were used. Previous studies on B cell development and
      differentiation in GF-CD mice have demonstrated a high reduction in the number of
      cells secreting Ig of the non-IgM isotypes but an Ig-VH gene usage and a B cell
      specificity repertoire that is substantially different from that observed in
      conventional adult mice and more closely resembles that of neonatal conventional
      mice. In contrast, the present comparison of the various lymphocyte populations
      in the thymus, lymph nodes, and spleen from GF-CD and conventional mice using
      flow cytometry analysis revealed no significant differences. Analysis of the TCR
      V beta expression on both mature thymocytes and lymph node T cells showed a high
      degree of similarity between GF-CD and conventional mice. These findings indicate
      a marked difference in the influence of exogenous antigenic stimulation on the
      development of B and T cells. Additionally, development in an environment free of
      exogenous antigenic stimulation allows for full functional maturation of T cells
      to occur, because MLC showed that GF-CD splenic T cells could mount allogeneic
      responses in a way similar to T cells generated in a conventional environment.
      Most importantly, full Th cell function is generated, because activation of GF-CD
      spleen cells by cross-linking with mAb against CD3 resulted in the induction of
      cells secreting IFN-gamma and Ig of the non-IgM isotypes, which cannot be
      detected in GF-CD sera. These findings demonstrate that functional T and B cells
      develop in mice that have not been exposed to exogenous Ag, and that the TCR
      repertoire, in contrast to the B cell compartment, is predominantly shaped by
      endogenously expressed Ag.

PMID- 1386860
TI  - Cytokine production by mature and immature CD4-CD8- T cells. Alpha beta-T cell
      receptor+ CD4-CD8- T cells produce IL-4.
AB  - This study follows our previous investigation describing the production of four
      cytokines (IL-2, IL-4, IFN-gamma, and TNF-alpha) by subsets of thymocytes defined
      by the expression of CD3, 4, 8, and 25. Here we investigate in greater detail
      subpopulations of CD4-CD8- double negative (DN) thymocytes. First we divided
      immature CD25-CD4-CD8-CD3- (CD25- triple negative) (TN) thymocytes into CD44+ and
      CD44- subsets. The CD44+ population includes very immature precursor T cells and
      produced high titers of IL-2, TNF-alpha, and IFN-gamma upon activation with
      calcium ionophore and phorbol ester. In contrast, the CD44- subset of CD25- TN
      thymocytes did not produce any of the cytokines studied under similar activation
      conditions. This observation indicates that the latter subset, which
      differentiates spontaneously in vitro into CD4+CD8+, already resembles CD4+CD8+
      thymocytes (which do not produce any of the tested cytokines). We also subdivided
      the more mature CD3+ DN thymocytes into TCR-alpha beta- and TCR-gamma delta
      bearing subsets. These cells produced cytokines upon activation with solid phase
      anti-CD3 mAb. gamma delta TCR+ DN thymocytes produced IL-2, IFN-gamma and TNF
      alpha, whereas alpha beta TCR+ DN thymocytes produced IL-4, IFN-gamma, and TNF
      alpha but not IL-2. We then studied alpha beta TCR+ DN T cells isolated from the
      spleen and found a similar cytokine production profile. Furthermore, splenic
      alpha beta TCR+ DN cells showed a TCR V beta gene expression profile reminiscent
      of alpha beta TCR+ DN thymocytes (predominant use of V beta 8.2). These
      observations suggest that at least some alpha beta TCR+ DN splenocytes are
      derived from alpha beta TCR+ DN thymocytes and also raises the possibility that
      these cells may play a role in the development of Th2 responses through their
      production of IL-4.

PMID- 1386861
TI  - Regulation of human monocyte cell-surface and soluble CD23 (Fc epsilon RII) by
      granulocyte-macrophage colony-stimulating factor and IL-3.
AB  - We have investigated the regulation of expression of cell-surface and soluble
      CD23 (sCD23) by purified human peripheral blood monocytes and in cultures of
      human whole blood. IL-3, IL-4, and GM-CSF were found to markedly enhance the
      expression of CD23 on the surface of elutriated monocytes and to increase levels
      of sCD23 in monocyte-culture supernatants. The induction of CD23 expression by
      monocytes was confirmed at the mRNA level by Northern blot analysis. The ability
      of GM-CSF, IL-3, or IL-4 to induce cell-surface CD23 on monocytes was inhibited
      by specific neutralizing antibodies to the corresponding cytokine. IL-3 and GM
      CSF induced maximal surface CD23 expression on monocytes by 24 to 48 h, followed
      by a slight decline at 72 and 96 h. In contrast, IL-4 induced a progressive
      increase in monocyte CD23 expression that reached a maximum at approximately 72
      h. IL-4, GM-CSF, and IFN-gamma increased both surface and soluble CD23 expression
      by the monocytic cell line U937, whereas IL-3 had no effect. The plasma from
      fresh human whole blood or nonstimulated whole blood cultured for 24 to 48 h
      contained detectable sCD23, and addition of IL-3, IL-4, or GM-CSF to these
      cultures resulted in increased levels of this molecule. Two-color flow cytometry
      revealed that IL-3, but not GM-CSF, also enhanced CD23 expression by B cells
      enriched from PBMC, although the effect of IL-3 was weak in comparison with that
      of IL-4. These findings may have important implications for the in vivo
      therapeutic use of these cytokines.

PMID- 1386862
TI  - IL-4 reciprocally regulates IL-1 and IL-1 receptor antagonist expression in human
      monocytes.
AB  - Activation of human monocytes with LPS induces coordinate expression of a number
      of cytokine genes, including IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, and IL-8.
      The T cell-derived lymphokine, IL-4, inhibits expression of these genes in
      monocytes, suggesting that it may be an important physiologic regulator of
      cytokine production. We have previously shown that IL-4 reduces steady state
      messenger RNA (mRNA) levels for IL-1 beta in human monocytes by decreasing both
      IL-1 beta transcription and the t1/2 of newly formed IL-1 beta mRNA transcripts.
      In the present study, we extend these findings to show that IL-4 similarly
      accelerates the turnover of IL-6 mRNA in LPS-stimulated monocytes. However, this
      inhibition of cytokine expression and dramatic increase in the decay rate of
      cytokine mRNA does not extend to all LPS-inducible genes because IL-4 treatment
      did not inhibit the expression or accelerate the turnover of mRNA for the IL-1
      receptor antagonist (IL-1ra) in the same cells. Although IL-1 beta and IL-1Ra are
      both LPS-inducible genes, they displayed distinct temporal patterns of
      expression. Peak steady state mRNA levels for IL-1ra lagged significantly behind
      that of IL-1 beta, suggesting a possible endogenous mechanism for limiting IL-1
      biologic activity. Furthermore, although IL-4 suppressed expression of both IL-1
      beta and IL-6, it up-regulated synthesis of IL-1ra mRNA and protein. Thus, IL-4
      inhibits production of the proinflammatory cytokine, IL-1 beta, while
      concomitantly enhancing synthesis of the IL-1ra in activated human monocytes.

PMID- 1386863
TI  - Murine recombinant Fc gamma RIII, but not Fc gamma RII, trigger serotonin release
      in rat basophilic leukemia cells.
AB  - Murine Fc gamma RII and Fc gamma RIII have highly homologous extracellular
      domains, but unrelated transmembrane and intracytoplasmic (IC) domains. Murine Fc
      gamma RIIb1 and b2 are two isoforms of single-chain receptors which differ only
      by 47 aa in their IC domain. Murine Fc gamma RIII are composed of an IgG-binding
      alpha-chain, the intracellular portion of which is unrelated to that of Fc gamma
      RII, and of a homodimeric gamma-chain which also associates with Fc epsilon RI.
      Murine mast cells express Fc gamma RII, Fc gamma RIII, and Fc epsilon RI. They
      can be induced to degranulate by murine IgG immune complexes or by F(ab')2
      fragments of the rat anti-murine Fc gamma RII/III mAb 2.4G2, complexed to mouse
      anti-rat (MAR) F(ab')2. In order to determine which murine Fc gamma R can
      activate mast cells, cDNA encoding murine Fc gamma RIIb1, Fc gamma RIIb2 or Fc
      gamma RIII alpha were stably transfected into RBL-2H3 cells. Murine Fc gamma RIII
      but not Fc gamma RIIb1 or Fc gamma RIIb2 induced serotonin release when
      aggregated by (2.4G2-MAR) F(ab')2 complexes. The respective roles of the IC
      domains of murine Fc gamma RIII subunits in signal transduction were investigated
      by stably transfecting cDNA encoding IC-deleted or chimeric murine Fc gamma R
      into RBL-2H3 cells. The substitution of the IC domain of murine Fc gamma RII for
      that of murine Fc gamma RIII gamma, but not that of murine Fc gamma RIII alpha,
      conferred the ability to trigger serotonin release. The deletion of IC sequences
      of the alpha subunit did not alter the ability of murine Fc gamma RIII to trigger
      serotonin release. It follows that 1) murine Fc gamma RIII, but not Fc gamma RII,
      can induce RBL cells to release serotonin, 2) the aggregation of the IC domain of
      the murine Fc gamma RIII gamma subunit is sufficient, but 3) the IC domain of the
      murine Fc gamma RIII alpha subunit is neither sufficient nor necessary for
      triggering serotonin release.

PMID- 1386864
TI  - Expression of complement components of the alternative pathway by glioma cell
      lines.
AB  - Glioma cell lines express proteins of the complement alternative pathway, namely
      C3, factor B, factor H, and factor I. Secretion of these proteins was shown by a
      sensitive and specific ELISA. C3 and factor H were rapidly secreted by glioma
      cell line CB193 and reached a concentration of 140 ng/ml/10(6) cells after 72 h
      of culture. Factor B and factor I were secreted at a lower rate and reached
      concentrations of 25 and 15 ng/ml/10(6) cells, respectively. Western blot and
      immunoprecipitation experiments showed that secreted proteins were identical to
      the corresponding plasma proteins. For factor H, besides the well known 150-kDa
      species, an additional polypeptide of 45 kDa with factor H immunoreactivity was
      observed. This species corresponded to the N-terminal truncated form found in
      plasma. In preliminary experiments, we observed control of these syntheses by
      cytokines. IL-1 beta significantly increased C3 secretion, with no effect on
      factor H. Secretion of factor H was enhanced by IFN-gamma. These results show
      that a glioma cell line could be a useful tool to study complement biosynthesis
      by glial cells in humans.

PMID- 1386865
TI  - Early recognition of a discordant xenogeneic organ by human circulating
      lymphocytes.
AB  - Cell-mediated immune mechanisms underlying discordant xenograft rejection are
      poorly characterized. In our study, using a human to rat xenogeneic ex vivo
      model, we show that a fraction of human lymphocytes, when perfused through the
      coronary system of a rat heart, rapidly and specifically adheres to the vascular
      endothelium and infiltrates the myocardium. Lymphocyte phenotypic analysis before
      and after perfusion, as well as the use of purified cell subpopulations,
      demonstrate preferential adhesion of CD3- CD16+ NK cells. NK cell adhesion occurs
      via xenoreactive antibody-dependent and -independent pathways, because the
      selective removal of human IgG from the perfusion buffer markedly reduces but
      does not completely abrogate NK cell sequestration. However, T lymphocytes are
      retained in the xenoorgan via an antibody-independent pathway, as assessed by the
      lack of influence of IgG removal. Leukocyte integrins appear to play a crucial
      role in mediating adhesion of both lymphocyte subsets, because the pretreatment
      of lymphocytes with anti-CD11a, anti-CD11b, and anti-CD18 antibodies markedly
      reduces their retention into the xenogeneic organ. Retained human lymphocytes
      mediate rapid and direct damage of the xenoorgan, as demonstrated by histologic
      and functional alterations of the endothelium, impaired vascular resistance and
      in vitro lysis of rat endothelial cells by human NK cells. Taken together, these
      findings suggest a role for cell-mediated mechanisms in the rapid recognition and
      rejection of vascularized xenografts.

PMID- 1386866
TI  - Class I restricted CTL recognition of a soluble protein delivered by liposomes
      containing lipophilic polylysines.
AB  - CD8+ cytotoxic lymphocytes recognize peptides derived from endogenous antigens
      complexed with class I major histocompatibility complex while CD4+ helper cells
      recognize peptides from exogenous antigens bound to class II MHC molecules. A
      soluble protein can be introduced into the class I pathway of antigen processing
      and presentation using an appropriate vehicle to deliver the antigen into the
      cytosol. Cationic liposomes containing lipophilic polylysine readily form
      complexes with an anionic, soluble protein ovalbumin. Mouse thymoma EL4 cells
      incubated with such complexes can be sensitized for killing by OVA-specific CTL
      effector cells. This method of target sensitization by a soluble antigen is more
      sensitive than the osmotic loading method previously reported.

PMID- 1386867
TI  - Increased expression of CD23 on peripheral blood B cells and
      macrophages/monocytes during acute infectious mononucleosis.

PMID- 1386868
TI  - [Inhibitory effects of calphobindins on phospholipase A2 and phospholipase C].
AB  - Calphobindins (CPBs) I, II and III which we isolated and characterized from
      placenta belong to a family of calcium and phospholipid binding proteins
      represented by lipocortins known to inhibit phospholipase A2(PLA2). The amino
      acid sequence of three CPBs shares much homology with lipocortins I and II, so we
      investigated the functions of CPBs in affecting the enzymatic activities of PLA2
      and also phospholipase C(PLC). In our experiments CPBs I, II and III showed an
      apparent dose-dependent inhibition of PLA2 and PLC activities, and all three
      proteins had a more potent inhibitory effect than lipocortins. The inhibition was
      overcome by high phospholipid substrate concentrations, for example, in the
      presence of 2.9 x 10(-9)M PLA2 and 2.6 x 10(-7)M CPB I, the inhibition decreased
      from 85 to 9% as phosphatidylethanolamine was increased from 10 to 100 microM. A
      similar result was observed in the case of PLC also. The evidence strongly
      suggests that the inhibitory effect of CPBI results from binding of the proteins
      to the phospholipid substrate rather than from a direct action on the
      phospholipase itself.

PMID- 1386869
TI  - [A case of choriocarcinoma assessed by transvaginal color Doppler].

PMID- 1386870
TI  - Induction of gamma/delta T cells in murine salmonellosis by an avirulent but not
      by a virulent strain of Salmonella choleraesuis.
AB  - To elucidate the relationship between the virulence of intracellular bacterium
      and its ability to induce gamma/delta T cells in the host during infection, we
      examined the differences in appearance of gamma/delta T cells in mice infected
      with Salmonella choleraesuis virulent strain RF-1 carrying a virulence plasmid of
      50 kb, and with avirulent strain 31N-1 cured of the 50-kb plasmid. The number of
      gamma/delta T cells in the peritoneal cavity was increased to a significant level
      on day 3 after an intraperitoneal infection with a sublethal dose (5 x 10(4)
      colony-forming units) of avirulent strain 31N-1. On the other hand, no increase
      in the number of gamma/delta T cells was evident in the peritoneal cavity at any
      stage after infections with various doses of virulent strain RF-1, although the
      numbers of the bacteria were drastically increased. Similar to that seen in the
      peritoneal cavity, the number of gamma/delta T cells in the liver was
      significantly increased after an intraperitoneal infection with avirulent strain
      31N-1 but not with virulent strain RF-1. The early appearing gamma/delta T cells
      during salmonellosis with avirulent stain 31N-1, which preferentially used V
      gamma 1/V delta 6, showed blastogenesis in response to purified protein
      derivative (PPD) derived from Mycobacterium tuberculosis. The gamma/delta T cells
      also responded to the peritoneal adherent cells in mice infected with avirulent
      strain 31N-1 6 d previously, which expressed a high level of endogenous heat
      shock protein (hsp) homologous to the mycobacterial 65-kD hsp. The expression of
      the hsp, however, was not prominent in the adherent cells in mice infected with
      virulent strain RF-1. These results suggest that the gamma/delta T cells specific
      for PPD may play important roles in host defense against murine salmonellosis,
      and that the virulence of Salmonella may be inversely correlated with its ability
      to induce endogenous hsp in the infected macrophages, which in turn stimulate the
      gamma/delta T cells in the host during salmonellosis.

PMID- 1386871
TI  - Expression of a transgenic T cell receptor beta chain enhances collagen-induced
      arthritis.
AB  - SWR/J transgenic (tg) mice were generated expressing the TCR beta chain derived
      from an anticollagen type II (CII) arthritogenic T cell clone. The SWR/J strain
      was selected because it is resistant to collagen-induced arthritis (CIA) and
      lacks the V beta gene segment used by the T cell clone. Expression of the tg beta
      chain on all thymocytes and peripheral lymph node T cells led to a more efficient
      anti-CII immune response, but did not confer CIA susceptibility to SWR/J mice.
      Nevertheless, this tg beta chain enhanced predisposition to CIA as (DBA/1 x SWR)
      F1 beta tg mice were more susceptible than normal F1 littermates. Our results
      demonstrate that the expression of the tg beta chain contributes to CIA
      susceptibility, but by itself it is not sufficient to overcome CIA resistance in
      the SWR/J strain.

PMID- 1386872
TI  - Demonstration of a second ligand for the low affinity receptor for immunoglobulin
      E (CD23) using recombinant CD23 reconstituted into fluorescent liposomes.
AB  - Recombinant full-length human CD23 has been incorporated into fluorescent
      liposomes to demonstrate the existence of a ligand for CD23 that is different
      from the previously known ligand, immunoglobulin E (IgE). The novel ligand for
      CD23 is expressed on subsets of normal T cells and B cells as well as on some
      myeloma cell lines. The interaction of full-length CD23 with its ligand is
      specifically inhibited by anti-CD23 monoclonal antibodies and by IgE, and it is
      Ca2+ dependent. Moreover, tunicamycin treatment of a CD23-binding cell line, RPMI
      8226, significantly reduced the binding of CD23 incorporated into fluorescent
      liposomes, and a sugar, fucose-1-phosphate, was found to inhibit CD23-liposome
      binding to RPMI 8226 cells, suggesting the contribution of sugar structures on
      the CD23 ligand. In addition, CD23-transfected COS cells were shown to form
      specific conjugates with the cell line RPMI 8226. These data demonstrate that
      CD23 interacts with a ligand, which is different from IgE, and that CD23 can be
      considered as a new surface adhesion molecule involved in cell-cell interactions.

PMID- 1386873
TI  - Identification of the low affinity receptor for immunoglobulin E on mouse mast
      cells and macrophages as Fc gamma RII and Fc gamma RIII.
AB  - In addition to their well characterized high affinity immunoglobulin E (IgE)
      receptors (Fc epsilon RI) mast cells have long been suspected to express
      undefined Fc receptors capable of binding IgE with low affinity. In this paper,
      we show that Fc gamma RII and Fc gamma RIII, but not Mac-2, on mouse mast cells
      and macrophages bind IgE-immune complexes. This binding is efficiently competed
      by 2.4G2, a monoclonal antibody against the extracellular homologous region of
      both Fc gamma RII and Fc gamma RIII. Furthermore, IgE-immune complexes bind
      specifically to Fc gamma RII or Fc gamma RIII transfected into COS-7 cells. The
      association constants of IgE binding estimated from competition experiments are
      about 3.1 x 10(5) M-1 for Fc gamma RII, and 4.8 x 10(5) M-1 for Fc gamma RIII.
      Engagement of Fc gamma RII and Fc gamma RIII with IgE-immune complexes (after
      blocking access to Fc epsilon RI) or with IgG-immune complexes triggers C57.1
      mouse mast cells to release serotonin. This release is inhibited by 2.4G2, and at
      maximum, reaches 30-40% of the intracellular content, about half of the maximal
      release (60-80%) obtained after Fc epsilon RI engagement. These data demonstrate
      that mouse Fc gamma RII and Fc gamma RIII are not isotype specific, and that the
      binding of IgE-immune complexes to these receptors induces cell activation.

PMID- 1386874
TI  - Mechanisms of mouse spleen dendritic cell function in the generation of influenza
      specific, cytolytic T lymphocytes.
AB  - We have evaluated the capacity of dendritic cells to function as antigen
      presenting cells (APCs) for influenza and have examined their mechanism of
      action. Virus-pulsed dendritic cells were 100 times more efficient than bulk
      spleen cells in stimulating cytotoxic T lymphocyte (CTL) formation. The induction
      of CTLs required neither exogenous lymphokines nor APCs in the responding T cell
      population. Infectious virus entered dendritic cells through intracellular acidic
      vacuoles and directed the synthesis of several viral proteins. If ultraviolet
      (UV)-inactivated or bromelain-treated viruses were used, viral protein synthesis
      could not be detected, and there was poor induction of CTLs. This indicated that
      dendritic cells were not capable of processing noninfectious virus onto major
      histocompatibility complex (MHC) class I molecules. However, UV-inactivated and
      bromelain-treated viruses were presented efficiently to class II-restricted CD4+
      T cells. The CD4+ T cells crossreacted with different strains of influenza and
      markedly amplified CTL formation. Cell lines that lacked MHC class II, and
      consequently the capacity to stimulate CD4+ T cells, failed to induce CTLs unless
      helper lymphokines were added. Similarly, dendritic cells pulsed with the MHC
      class I-restricted nucleoprotein 147-155 peptide were poor stimulators in the
      absence of exogenous helper factors. We conclude that the function of dendritic
      cells as APCs for the generation of virus-specific CTLs in vitro depends
      measurably upon: (a) charging class I molecules with peptides derived from
      endogenously synthesized viral antigens, and (b) stimulating a strong CD4+ helper
      T cell response.

PMID- 1386875
TI  - Differentiation of CD3-4-8- thymocytes in short-term thymic stromal cell culture.
AB  - We have investigated the ability of a heterogeneous thymic stromal cell (HTSC)
      culture system to promote in vitro differentiation of CD3-4-8- thymocytes.
      Culture of purified murine CD3-4-8- thymocytes on HTSC for 1 d resulted in the
      appearance of CD4+8+ cells, which did not occur when the sorted cells were
      maintained in medium alone. It is remarkable that when the culture period was
      extended to 2 d, CD3-4-8- progenitors differentiated further to CD4+8- and CD4-8+
      cells, which also expressed high levels of TCR-CD3. This rapid differentiation on
      stroma in vitro appears to outpace parallel development in vivo. The
      differentiation potential of a subset of CD3-4-8- thymocytes that express high
      levels of a marker of normal and neoplastic thymic progenitors, the 1C11 antigen,
      was examined next. 1C11hiCD3-4-8- cells also gave rise to CD4-8+ and CD4+8+
      populations after 1 d of culture on HTSC. Extending the culture period to 2 d
      resulted in a significant percentage of CD3-expressing cells that were CD4+8+,
      CD4+8- and CD4-8+ cells. These results suggest that in the in vitro HTSC culture
      system, various subsets of immature thymocytes can differentiate into all the
      mature phenotypes of cells normally found in the adult mouse thymus. This may
      provide a novel and rapid assay for thymic progenitors.

PMID- 1386877
TI  - Human neutrophils produce high levels of the interleukin 1 receptor antagonist in
      response to granulocyte/macrophage colony-stimulating factor and tumor necrosis
      factor alpha.
AB  - Neutrophils, an abundant cell type at sites of inflammation, have the ability to
      produce a number of cytokines, including interleukin 1 (IL-1), IL-8, granulocyte
      macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha
      (TNF-alpha). In this study, we have examined the ability of human neutrophils to
      produce the IL-1 receptor antagonist (IL-1Ra), a 17-23-kD protein recently
      isolated and cloned from macrophages. Since IL-1Ra has been shown to inhibit both
      the in vitro and in vivo effects of IL-1, its production by large numbers of
      tissue-invading neutrophils might provide a mechanism by which the effects of IL
      1 are regulated in inflammation. Using antibodies that are specific for IL-1Ra
      and a cDNA probe encoding for this protein, we were able to show that neutrophils
      constitutively produce IL-1Ra. However, after activation by GM-CSF and TNF-alpha,
      IL-1Ra was secreted into the extracellular milieu where it constituted the major
      de novo synthesized product of activated neutrophils. None of a large array of
      other potent neutrophil agonists were found to affect the production of IL-1Ra by
      neutrophils. Quantitative measurements by enzyme-linked immunosorbent assay
      revealed that intracellular IL-1Ra is in eightfold excess of the amount secreted
      in supernatants when studying nonactivated neutrophils. However, in GM-CSF- and
      TNF-alpha-activated cells, this difference was reduced to values between four-
      and fivefold, as virtually all of the de novo synthesized IL-1Ra was secreted. In
      activated cells, the intracellular content of IL-1Ra was found to be in the 2-2.5
      ng/ml range per 10(6) neutrophils, whereas levels reached the 0.5-ng/ml range in
      supernatants. This would imply that IL-1Ra is produced in excess of IL-1 by a
      factor of at least 100, an observation that is in agreement with the reported
      amounts of IL-1Ra needed to inhibit the proinflammatory effects of IL-1.
      Neutrophils isolated from an inflammatory milieu, the synovial fluid of patients
      with rheumatoid arthritis, were found to respond to GM-CSF and TNF-alpha in terms
      of IL-1Ra synthesis, indicating that the in vitro observations made in this study
      are likely to occur in an inflammatory setting in vivo.

PMID- 1386878
TI  - A quantitative autoradiographic study of 125I atrial natriuretic factor in the
      heart of a teleost fish (Conger conger).
AB  - Quantitative receptor autoradiographic study of 125I-atrial natriuretic peptide
      factor (ANF) in the heart of a teleost fish Conger conger has shown that a
      heterogenous distribution of 125I-ANF binding exists in the different cardiac
      regions. Elevated ANF binding densities (3,790 fmol/mg protein) were encountered
      in the innermost layer (tunica intima) of the bulbus arteriosus while lower
      binding levels (293-403 fmol/mg protein) were revealed in atrium and ventricle.
      In order to determine 125I-ANF binding characteristics (KD, Bmax) in the above
      cardiac sites, saturation binding assays were carried out. The results show that
      low 125I-ANF KD values (28.8-52.6 pM) were found in the atrium and in the bulbus
      arteriosus with respect to the higher KD values (373 pM) of the ventricle. The
      number of binding sites were respectively 632 and 1,279 fmol/mg protein for the
      atrium and the ventricle, while a substantially elevated Bmax of 7,235 fmol/mg
      protein was found for the bulbus arteriosus. These results may furnish some
      insights concerning ANF receptor binding activity and its putative regulatory
      role of different cardiac functions.

PMID- 1386879
TI  - Fourier transform infrared analyses of some particulate drug mixtures using a
      diamond anvil cell with a beam condenser and an infrared microscope.
AB  - Although the diamond anvil cell (DAC) has been used in many forensic science
      laboratories for the analysis of trace evidence, few applications of this
      technique for the analysis of controlled substances have been reported. This may
      be due to both an unfamiliarity on the part of forensic drug chemists with this
      accessory and the nature and quality of spectra that result from use of a DAC on
      a dispersive instrument. Along with low energy throughput, which results in
      relatively high noise levels, strong broad diamond absorptions occur. With the
      use of a Fourier transform infrared instrument, these do not present a problem
      and nanogram quantities of materials can be analyzed when the DAC is used with an
      infrared microscope. Since single crystals can be sampled with the DAC, simple
      physical separations (involving particle-picking) can be used in certain cases to
      isolate drugs from particulate mixtures for infrared analysis. This method is
      especially useful for some "difficult" mixtures and residues, and several
      examples of such analyses involving samples of forensic science interest are
      presented.

PMID- 1386880
TI  - Visualization method for fingerprints on skin by impression on a polyethylene
      terephthalate (PET) semirigid sheet.
AB  - Based on the phenomenon that static electricity attracts dust, a polyethylene
      terephthalate (PET) semirigid sheet coated with printing ink was used to
      visualize impressions of fingerprints on the skin of living and dead bodies.
      Compared with visualization methods for perspiration fingerprints, this method
      recovers better images for a longer time after the fingerprint has been deposited
      on skin. Fingerprints transferred to the PET sheet are photographed with
      sidelighting using an ordinary light source. For fingerprints that yield
      inadequate contrast, an argon-ion laser can be used to improve the contrast.

PMID- 1386876
TI  - A fail-safe mechanism for maintaining self-tolerance.
AB  - Using cytotoxic T lymphocyte (CTL) responses to the class I histocompatibility
      antigen Qa1 and to the minor histocompatibility antigen H-Y, we show that the
      immune system maintains a peripheral screening process that is able to tolerize a
      wide variety of potentially autoimmune CTL. The critical factor is the presence
      or absence of specific T helper cells. If T help is available, CTL precursors
      that recognize antigen are activated. In the absence of help, they are tolerized.
      Thus, T helper cells are guardians of peripheral tolerance in CTL.

PMID- 1386881
TI  - Protein C, protein S and C4b-binding protein in neonatal severe infection and
      septic shock.
AB  - We have studied the behaviour of total protein S, free protein S, protein C and
      C4b-binding protein fifteen neonates with severe infections, eight with septic
      shock and in a group of ten healthy newborns. Protein C was decreased in shock
      and septic patients, but only the shock group showed significant differences
      compared to normal neonates. Total protein S was normal in both groups of
      patients, although free protein S had significantly lower values in shock and
      nonshock infants. C4b-binding protein was higher than normal in septic and shock
      patients compared to the control group. Decreased values of protein C and free
      protein S can be explained by the activation of coagulation and their subsequent
      consumption. On the other hand, the increased levels of C4b-binding protein can
      affect the distribution of protein S in plasma, producing a shift in protein S to
      the complexed inactive form. These findings can contribute to an increased risk
      of microthrombosis during neonatal sepsis.

PMID- 1386882
TI  - Sensitization to the toxic effects of cocaine in mice is associated with the
      regulation of N-methyl-D-aspartate receptors in the cortex.
AB  - Repeated exposure to cocaine results in sensitization to many of the behavioral
      effects of the drug. The present study was undertaken to examine the role of the
      N-methyl-D-aspartate (NMDA) type of glutamate receptors in the development of
      sensitization to the convulsive and lethal effects of cocaine in Swiss Webster
      mice. Repeated administration of subconvulsant doses of cocaine (45 mg/kg for 7
      days) produced a progressive increase in the convulsive responsiveness to the
      drug. This phenomenon was accompanied by an increase in lethality rate after the
      5th day of the treatment. Pretreatment with the noncompetitive NMDA receptor
      antagonist, MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]- cyclohepten-5,10
      imine) abolished completely the development of sensitization to cocaine-induced
      seizures and lethality. In addition, MK-801 attenuated cocaine-induced loss in
      animals body weight after 7 days of drug treatment. The lethal effects of acute
      administration of increasing doses of cocaine were also reduced by pretreatment
      with MK-801. In vitro receptor binding experiments demonstrated an increase (139%
      of control) in the number of NMDA receptors, labeled with the competitive NMDA
      receptor antagonist [3H]CGP 39653 ([3H]-2-amino-4-propyl-5-phosphono-3-pentenoic
      acid), in cortical membranes derived from the mice treated for 7 days with
      cocaine (45 mk/kg). In agreement with the latter finding, binding of [3H]MK-801
      to the phencyclidine/NMDA site in cortical membranes of cocaine-treated mice was
      more sensitive to the stimulatory effect of glutamate compared to control (saline
      treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386883
TI  - Mast cell mediators regulate vascular permeability changes in Arthus reaction.
AB  - Plasma exudation characterizes the early phase of acute inflammation. The
      possible role of mast cells and their mediators in this event in immune complex
      induced injury was studied. Dye exudation was assessed from 5 min to 2 hr after
      initiating reverse passive Arthus reaction in mast cell-deficient mice, WBB6F1
      W/Wv (W/Wv), and their normal congenic controls, WBB6F1-+/+ (+/+). The response
      to antibody (10, 30 and 100 micrograms/site, i.d.) was dose- and time-dependent
      in both groups of mice. At the lower doses of antibody, 10 and 30
      micrograms/site, exudation was significantly less (30% and 40%, respectively) in
      W/Wv as compared to +/+ mice between 15 to 45 min. With 100 micrograms of
      antibody/site, significant differences between W/Wv and +/+ mice were noted only
      at 15 and 30 min. The deficit in permeability changes in W/Wv mice was reversed
      by local mast cell reconstitution. In +/+ mice, pyrilamine and methysergide
      pretreatment reduced vascular permeability to the same extent by 70, 60 and 35%
      when stimulated for 30 min with 10, 30 and 100 micrograms of antibody/site,
      respectively. An equivalent inhibition was observed with the 5-lipoxygenase
      inhibitor A-63162. None of the inhibitors decreased plasma permeation in W/Wv
      mice. These results indicate that the mast cell mediators histamine and serotonin
      regulate vascular permeability early during an immune complex-mediated
      inflammation. The data also suggest the involvement of leukotrienes and the
      importance of mast cells in their synthesis. The profile of inhibition in +/+
      mice agrees well with the difference in exudation observed between normal and
      mast cell-deficient mice.

PMID- 1386884
TI  - Effect of short-term treatment with gastrin and related peptides on
      gastrointestinal histamine H2-receptors.
AB  - The effects of short-term, 7-day, treatment with synthetic 15-leucine human
      gastrin I, pentagastrin or sulfated cholecystokinin-8 on the activity of
      histamine (HA)-stimulated adenylate cyclase in membranes isolated from guinea pig
      gastric mucosa and H2-receptor-mediated contractions of isolated ilea were
      evaluated. Treatment with each of the peptides produced a decrease in the maximal
      rate of HA-stimulated adenylate cyclase. The decreases in the maximal rate
      occurred without any effect on the potency of HA or any effect on basal rates of
      activity. In animals treated with pentagastrin, but not with cholecystokinin
      octapeptide sulfate, the contractile activity of dimaprit, a selective H2
      agonist, was decreased. In animals treated with pentagastrin, the contractile
      actions of pentagastrin on isolated ileal preparations were increased. A 7-day
      treatment with the H2-antagonist, tiotidine, did not alter the potency of or the
      maximal response for HA-stimulated adenylate cyclase activity. Co-treatment with
      tiotidine prevented the effects of pentagastrin on gastric mucosal HA-stimulated
      adenylate cyclase. Treatment with pentagastrin did not alter the sensitivity of
      the gastric mucosal H2-receptor to inhibition by tiotidine. The effects of
      treatment with gastrin on NaF-stimulated adenylate cyclase activity also were
      determined. Treatment with gastrin did not alter the actions of NaF, suggesting
      that the coupling between the Gs subunit and the catalytic subunit of adenylate
      cyclase was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386885
TI  - 7-[(1R,2S,3S,5R)-6,6-dimethyl-3-(4- iodobenzenesulfonylamino)bicyclo[3.1.1]hept-2
      yl]-5(Z)-heptenoic acid: a novel high-affinity radiolabeled antagonist for
      platelet thromboxane A2/prostaglandin H2 receptors.
AB  - A high-affinity thromboxane (TX)A2/prostaglandin (PG) H2 receptor antagonist, I
      SAP [7-[(1R,2S,3S,5R)-6,6-dimethyl-3-(4-
      iodobenzenesulfonylamino)bicyclo[3.1.1]hept-2-yl]-5(Z)-heptenoic acid] and its
      radiolabeled analog [125I]SAP (Mais et al., 1991) are characterized in the
      present study. I-SAP antagonized I-BOP ([1S-(1 alpha, 2 beta(5Z),3
      alpha(1E,3R*),4 alpha)]-7-[3-(3-hydroxy-4- (4'-iodophenoxy)-1-butenyl)-7
      oxabicyclo-[2.2.1]heptan-2y l]-5'heptenoic acid) and U46619 [15S-hydroxy-11
      alpha,9 alpha-(epoxymethano)-prosta-5Z,13E-dienoic acid)], two different
      TXA2/PGH2 mimetics, induced aggregation of washed human platelets in a similar
      manner (pA2 of 8.11 +/- 0.09, Kd = 7.8 nM, n = 3; pA2 = 8.01 +/- 0.05, Kd = 9.7
      nM, n = 8, respectively). I-SAP also had agonistic activity, producing platelet
      shape change (EC50 = 9.7 nM +/- 0.6 nM at pH 7.4, n = 3) which was blocked by
      pretreatment of platelets with SQ29548 ([1S-(1 alpha,2 beta(5Z),3 beta,4 alpha)]
      7-[3-[[2- [(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept- 2-yl]
      5-heptenoic acid), a TXA2/PGH2 receptor antagonist. Radioligand binding studies
      were performed with [125I]SAP using washed human platelets. Competition of three
      agonists and four antagonists for binding with [125I]SAP was determined. The
      compounds showed the appropriate rank order potencies, including stereoselective
      competition by a pair of stereoisomeric antagonists. In washed human platelets,
      the Kd for I-SAP was 468 +/- 49 pM and the maximum binding (Bmax) was 2057 +/-
      156 sites/platelet at pH 7.4 (n = 6). The Bmax was significantly increased 49% to
      3072 +/- 205 sites/platelet at pH 6.5 (P less than .01 but the Kd was unchanged
      (490 +/- 18 pM, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386887
TI  - Actions of a 5-lipoxygenase inhibitor, Sch 40120, on acute inflammatory
      responses.
AB  - Sch 40120 (10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b] [1,8]naphthyridin
      5(7H)-one) is an inhibitor of the 5-lipoxygenase enzyme in rat neutrophils, human
      neutrophils and the the MC9 murine mast cell clone with IC50 values of 8, 4 and 7
      microM, respectively. The drug was examined for its effects on acute inflammatory
      responses in the paw and pleural cavity of rats. The drug suppressed paw
      inflammation triggered by a reverse passive Arthus reaction or a subplantar
      injection of the polysaccharide carrageenan with p.o. ED50 values of 0.2 and 1.5
      mg/kg, respectively. In reverse passive Arthus reaction and carrageenan pleurisy
      models, Sch 40120 was found to suppress both the cellular and fluid components of
      the acute inflammation. The p.o. ED50 values for inhibition of cells and fluid in
      pleurisy models were in the range of 0.1 to 0.7 mg/kg. When applied locally to
      the ears of mice, the drug blocked an arachidonic acid-induced and leukotriene
      mediated ear inflammation with an ED50 of 0.072 mg/ear. These findings suggest
      that Sch 40120 is a potent anti-inflammatory agent that may be particularly
      useful in the treatment of inflammatory diseases such as psoriasis in which
      leukotrienes appear to be major mediators of the pathological symptoms that
      characterize the disease state.

PMID- 1386886
TI  - Characterization of indole-2-carboxylate derivatives as antagonists of N-methyl-D
      aspartate receptor activity at the associated glycine recognition site.
AB  - We have synthesized a series of indole-2-carboxylate derivatives and, with the
      use of radioligand binding, electrophysiological techniques and an in vivo
      transient bilateral carotid occlusion model of ischemic damage known to be
      sensitive to NMDA antagonists, have evaluated the indole-2-carboxylate
      derivatives ability to inhibit N-methyl-D-aspartate (NMDA) receptor activity
      through the associated glycine modulatory site. By using [3H]glycine to label
      this modulatory site, we found that the compounds with the highest affinity (Ki
      less than 1 microM) contained a chloro group at position C-6 and a polar,
      hydrogen-bond-accepting group at position C-3 of the indole ring. When these
      compounds were tested for their ability to modulate [3H]MK-801 [(+)-[3H]-5-methyl
      10,11-dihydro-5H-dibenzo[a,d]cyclophepten-5,10- imine maleate) binding, a
      functional assessment of NMDA receptor activation, binding was inhibited,
      indicative of NMDA receptor antagonist character. Schild regression analysis
      indicated that this antagonism was competitive with glycine. Next, several of
      these indole-2-carboxylate derivatives were analyzed electrophysiologically in
      rat cortex mRNA-injected Xenopus oocytes shown to express a functional NMDA
      receptor channel complex. These compounds inhibited NMDA receptor activity in a
      manner noncompetitive with NMDA. They also produced a parallel right-ward shift
      in the glycine dose response for potentiation of the NMDA responses in the
      oocytes and thus provided further evidence for a competitive interaction at the
      glycine site. Finally, in vivo transient bilateral carotid artery occlusion
      experiments revealed that these compounds were capable of reducing the damage
      typically associated with an ischemic insult in Mongolian gerbil hippocampal
      neurons.

PMID- 1386888
TI  - In vitro characterization of a novel TXA2/PGH2 receptor ligand (S-145) in
      platelets and vascular and airway smooth muscle.
AB  - The stereoisomers of S-145, a novel thromboxane A2/prostaglandin H2 (TXA2/PGH2)
      receptor ligand, were compared to TXA2/PGH2 receptor antagonists, SQ29548 and
      BM13505 in guinea pig platelets, aortas and trachea. Equilibrium binding assays
      in platelets yielded Kd values (nanomolar) for (+)-S-145 (0.57 +/- 0.04), (-)-S
      145 (9.2 +/- 1.3), SQ29548 (11.1 +/- 0.70) and BM13505 (118 +/- 16). In aortas,
      the corresponding Kb values (nanomolar) were (0.014 +/- 0.002), (1.90 +/- 0.31),
      (16.8 +/- 3.3) and (142 +/- 29), respectively, whereas in trachea, the Kd values
      (nanomolar) were (0.019 +/- 0.004), (1.12 +/- 0.18), (1.94 +/- 0.30) and (18.99
      +/- 2.59), respectively. S-145 stereoisomers elicited platelet shape change
      stereoselectively that was characterized by EC50 values 8 to 16-fold higher than
      the EC50 values for these ligands to block aggregation induced by TXA2/PGH2
      mimetic, U44069. S-145 (+)- and (-)-isomers stereoselectively induced transient
      aortic contraction at concentrations 214,000- and 16,000-fold higher,
      respectively, than the corresponding Kb values in this tissue. S-145-induced
      platelet shape change and aortic contraction were inhibitable by low
      concentrations of SQ29548. We postulate that S-145 may elicit partial agonist
      activity in platelets and aorta via lower affinity for the active than inactive
      state of the TXA2/PGH2 receptor in those tissues. S-145 had no agonist activity
      in isolated trachea possibly indicating different TXA2/PGH2 recognition sites in
      aorta and trachea or a smaller preligand ratio of active to inactive TXA2/PGH2
      receptors in trachea than in aorta.

PMID- 1386889
TI  - Changes in discharge rate of fusimotor neurones provoked by fatiguing
      contractions of cat triceps surae muscles.
AB  - 1. Changes in discharge rate of thirty-one fusimotor neurones to triceps surae
      muscles during long-lasting, fatiguing contractions of these muscles were studied
      in decerebrate cats. Discharges of fusimotor neurones were recorded from the
      nerve filaments. Muscle contractions were elicited by electrical stimulation of
      either the muscle nerves (twenty-one neurones) or the corresponding ventral roots
      (ten neurones), until the muscle tension fell to about 30% of its initial value.
      2. Early and late changes could be recognized in fusimotor discharge rate during
      long-lasting muscle contraction. The early changes obviously not related to
      muscle fatigue, consisted of an initial increase at the onset of muscle
      contraction and a subsequent decrease to or below the resting discharge level.
      The late change in discharge rate, supposedly related to muscle fatigue, was an
      increase developing gradually towards the end of muscle contraction, ranging at
      its peak from 2 to 15 impulses/s (mean value 5.5 impulses/s, n = 31) and
      outlasting the contraction for 20-320 s. 3. When the contracting muscle was made
      ischaemic the late increase in fusimotor discharge rate started earlier and was
      maintained until the arterial clamp was removed. After severing the muscle nerves
      distal to the site of stimulation no changes, a slight sustained increase, or
      else a decrease in fusimotor discharge rate occurred during electrical
      stimulation of either muscle nerves or ventral roots. At its cessation the
      spontaneous firing rate was reassumed immediately. Stimulation of the distal
      stumps of the severed nerves elicited no changes in fusimotor discharge rate. 4.
      It is proposed that the late increase in fusimotor discharge rate may appear due
      to autogenetic excitation of fusimotor neurones by discharge from group III and
      IV muscle afferent fibres provoked and/or enhanced by metabolic products
      liberated in muscle tissue during the fatiguing contraction. The fusimotor firing
      was estimated to remain elevated to a level twice that of the spontaneous
      activity on average for approximately 120 s after the muscle contraction. Its
      functional role in muscle fatigue is discussed.

PMID- 1386891
TI  - Occlusal discrepancies after sealant therapy.
AB  - To date there has been no evidence concerning the need for adjusting the
      occlusion after sealant placement. Thus, this study investigated the occlusal
      effects of filled and unfilled sealants. For each of 18 subjects a sealant was
      applied and the occlusion monitored for 1 week. Each participant received a
      filled and an unfilled sealant for the specified period. With the filled sealant,
      nearly all subjects experienced a perceptable occlusal change and most were
      unable to abrade the interferences to a comfort level. These results indicate
      that the occlusion should be routinely verified and, if necessary, adjusted
      immediately after placement of a filled sealant.

PMID- 1386890
TI  - Muscle history dependence of responses to stretch of primary and secondary
      endings of cat soleus muscle spindles.
AB  - 1. Responses were recorded from both primary and secondary endings of soleus
      muscle spindles in the anaesthetized cat during slow stretches of the muscle
      after conditioning contractions at different lengths. 2. After a 5 mm length step
      and a fusimotor-strength contraction given at the longer length, on return to the
      initial length the response to a slow test stretch (0.5 mm s-1) showed a change
      in slope midway through the stretch which was attributed to taking up of slack in
      intrafusal fibres. 3. The onset of the change in slope during the test stretch
      depended on the size of the conditioning step. With no conditioning length
      change, just a fusimotor-strength contraction, there was no slope change and the
      response consisted of an initial burst followed by a maintained high rate of
      discharge. 4. Following a conditioning length step, the point of onset of the
      slope change during the test stretch could be altered by stimulating single
      identified fusimotor fibres to the spindle. Stimulating some static axons
      produced large changes in the stretch response while other static axons and
      dynamic axons had only small effects. 5. Many secondary endings showed a delay in
      onset of their response to a test stretch, dependent on the size of the preceding
      conditioning step, signalling the presence of slack in much the same way as the
      primary endings. Other secondary endings, however, appeared to have stretch
      responses that were largely independent of muscle conditioning. 6. Muscle history
      independent responses of secondary endings were associated with low axonal
      conduction velocities. It is proposed that secondary endings which remain
      unaffected by muscle conditioning lie on more distal regions of nuclear chain
      fibres in the S2-S5 position. Here they are stimulated during both the take-up of
      slack and the subsequent direct stretch of the intrafusal fibres.

PMID- 1386892
TI  - The radiologic features of cardiac rotation: a pictorial essay.
AB  - Rotation of the heart results from enlargement of individual cardiac chambers and
      influences significantly the configuration of the cardiomediastinal silhouette.
      Left ventricular enlargement leads to dextrorotation. Conversely, right
      ventricular enlargement leads to levorotation. The axis of rotation is nearly
      vertical and extends from the top of the aortic arch through the anterior wall of
      the left atrium and the proximal interventricular septum. Pericardial defect,
      deformity of the thoracic skeleton, and lower lobe atelectasis can also lead to
      cardiac rotation. An understanding of this concept facilitates the interpretation
      of chest radiographs in patients with heart disease. The terms clockwise and
      counterclockwise rotation of the heart should be abandoned.

PMID- 1386893
TI  - Effect of malnutrition on aerobic and anaerobic performance of fast- and slow
      twitch muscles of rats.
AB  - The effect of malnutrition on the functional properties of fast- and slow-twitch
      muscles from rats was studied using aerobic and anaerobic preparations. A 2-day
      fast and hypocaloric feeding to a weight loss of 25% were used as models of
      malnutrition. Soleus (slow-twitch) and extensor digitorum longus (EDL) (fast
      twitch) muscles were studied using an in situ preparation with the blood supply
      intact and an in vitro preparation to which cyanide had been added to render the
      muscles anaerobic. We found that a 2-day fast had little effect on the function
      of muscles stimulated in situ, whereas anaerobic stimulation produced a decrease
      in force per gram of muscle weight in the soleus, but not in the EDL, compared
      with control values. Hypocaloric feeding resulted in a slowed relaxation rate, an
      increased Fs/Fmax ratio, and an upward shift of the force-frequency curve
      relative to controls when studied in situ. Under anaerobic conditions, soleus
      muscles from hypocaloric rats continued to show a slow relaxation rate and
      demonstrated a loss of force per gram of muscle weight compared with controls,
      particularly at low stimulation frequencies. EDL muscles from hypocaloric rats
      had an increased relaxation rate and were able to maintain force with anaerobic
      stimulation. Soleus and EDL muscles from the fasted and hypocaloric groups had
      lower activities of phosphofructokinase. We conclude that slow-twitch muscles
      from malnourished rats are at a disadvantage when required to function under
      anaerobic conditions. These findings suggest that muscle performance may be
      impaired in malnourished patients subjected to hypoxia.

PMID- 1386895
TI  - Percutaneous transluminal angioplasty of an occluded distal splenorenal shunt.
AB  - A distal splenorenal (Warren) shunt was performed on a 39-year-old female with
      bleeding esophageal varices secondary to portal hypertension and cirrhosis. On
      the twelfth postoperative day, however, she rebled, and angiography revealed that
      the shunt was occluded. Using a percutaneous approach, successful balloon
      angioplasty and recanalization was performed. The patient did well and was
      discharged without further bleeding. Percutaneous transluminal angioplasty (PTA)
      appears to be effective in dilating occluded splenorenal shunts, obviating a
      second surgical procedure in high-risk patients.

PMID- 1386894
TI  - Toxicity of chemically generated nitric oxide towards pancreatic islet cells can
      be prevented by nicotinamide.
AB  - Previous studies have indicated that nitric oxide is involved in the lysis of
      pancreatic islet cells by inflammatory macrophages. Here we show that the
      incubation of islet cells with chemical NO-donors leads to cell lysis in a
      concentration and time dependent way. Islet cell death could be prevented by
      nicotinamide and 3-aminobenzamide, which are known to inhibit ADP-ribosylation,
      while several scavengers of oxygen radicals, N-acetylcysteine, dihydrolipoic
      acid, dimethylthiourea and citiolone, provided no protection.

PMID- 1386896
TI  - Operating a professional office under the ADA Act.

PMID- 1386897
TI  - Anatomy of a transcription factor important for the start of the cell cycle in
      Saccharomyces cerevisiae.
AB  - Entry of yeast cells into the mitotic cell cycle (Start) involves a form of the
      CDC28 kinase that associates with G1-specific cyclins encoded by CLN1 and CLN2
      (ref. 1). The onset of Start may be triggered by the activation of CLN1 and CLN2
      transcription in late G1 (ref. 2). SWI4 and SWI6 are components of a factor (SBF)
      that binds the CACGAAAA (SCB) promoter elements responsible for activation in
      late G1 of the HO endonuclease, CLN1 and CLN2 genes. A related factor (MBF)
      containing SWI6 and a 120K protein binds to the ACGCGTNA (MCB) promoter elements
      responsible for late G1-specific transcription of DNA replication genes. Nothing
      is known about how these heteromeric proteins bind DNA. We show here that SWI4
      contains a novel DNA-binding domain at its N terminus that alone binds
      specifically to SCBs and a C-terminal domain that binds to SWI6. SWI4's DNA
      binding domain is similar to an N-terminal domain of the cdc10 protein that is a
      component of an MBF-like factor from Schizosaccharomyces pombe and is required
      for Start. An involvement of this kind of DNA-binding domain in transcriptional
      controls at Start may therefore be a conserved feature of eukaryotic cells.

PMID- 1386898
TI  - Hepatitis B vaccination in dialysis patients and nutritional status.
AB  - 35 dialysis patients underwent anti-HBV vaccination. We classified patients in
      responders or non-responders using an anti-HBs titer of 50 UI/l as the
      discriminating serum level and tried to assess whether the antibody response
      bears any relationship with the nutritional status. 26 patients (74%) reached the
      target atb titer, which was maintained during follow-up (average 360 UI/l). The
      weak response in the other 9, with values never exceeding 20 UI/l, was short
      lived. Anthropometric and impedenziometric parameters were higher in responders
      than in nonresponders, but the difference did not reach statistical significance.
      We conclude that the atb titer which discriminates uremics in responders or not
      must be greater than 50 UI/l and that the nutritional status may interfere with
      the seroconversion rate, but this conclusion needs to be validated in a wider
      population.

PMID- 1386900
TI  - Epidemiology of viral hepatitis in dialysis centers: a national survey.
AB  - Because of the great problem of viral hepatitis in hemodialysis patients, the
      Italian Society of Nephrology decided to perform a national epidemiologic survey.
      We contacted 467 nephrological centers by a questionnaire which let us have
      information on 25,746 uremic patients: 18,338 on HD, 2,250 on PD and 5,176 with
      kidney transplant, respectively 78.5% of the total Italian dialysed patients and
      91.4% of the total transplanted patients. Statistical analyses were performed.
      HBV infections occur in 7.8% of the patients (2,008 cases) but considering that
      485 cases became spontaneously negative, the true overall incidence of chronic
      carriers falls to 4.9%. The main causes of the infection are reported as
      transfusions (64.3%) and dialysis environment (12%). The vaccination program
      performed by 93.2% of the centers, obtained an efficacious seroconversion in
      4,626 of 7,790 cases vaccinated: the vaccine currently most utilized is the
      recombinant type administered by means of 3 versus 4 boosters. In the 2nd part of
      the survey, we report information concerning the presence of nephropaties
      associated with HBV infections in nonuremic patients (208 cases). We present and
      discuss the clinical picture of the nephropaties, the hystologic bioptic pattern
      and the prognosis of the kidney pathology.

PMID- 1386899
TI  - HBV infection in hemodialysis patients: monitoring and prevention.
AB  - From 1986 to 91, 174 dialysis patients were studied. The prevalence of previous
      HBV infection and of chronic carriers was 33.3 and 4.6%, respectively.
      Immunization rate after vaccination (3 doses) was 63%. In 1991, we proposed a
      vaccination with 4 doses and recommend a 6-monthly anti-HBs evaluation to assess
      the timing of any booster dose needed.

PMID- 1386901
TI  - Hepatitis B vaccination in dialysis centres: advantages and limits.
AB  - A review is presented on the results achieved in HBV immunization of hemodialysis
      patients with aluminum-adsorbed, subunit plasma-derived and yeast-derived
      vaccines. The main host-related and immunization-related causes of low response
      are discussed. Various possibility to improve the vaccine performance through
      appropriate dosage and schedule, as well as immunopotentiating procedures are
      reported.

PMID- 1386902
TI  - Expectation of impaired response to recombinant hepatitis B vaccination.
AB  - A controlled trial of hepatitis B vaccination with recombinant antigen was
      undertaken in 18 hemodialysed end-stage renal failure (ESRD) patients (P) and 16
      members of our staff (controls, C). In order to identify expected nonresponders
      (NR), we monitored T lymphocyte (Tc) subsets, peripheral blood mononuclear cells
      (PBMC), total leukocytes (WBC) and IgG. After 3 vaccine doses of 40 and 20 IU,
      respectively, for P and C, at 0, 1 and 6 months, 11 P(61.1%) and all C (100%)
      responded, as in previous reports [1-3]. The 7 NR presented lower CD4+ Tc
      fraction, compared to responders (R) and C (p less than 0.05), and higher
      monocyte (p less than 0.00001) and WBC (p less than 0.002) counts, with lower
      lymphocyte fraction (p less than 0.001), compared to R. We suggest that NR could
      represent a selected group of ESRD patients, screenable by these easily
      detectable features, probably markers of a specific immune dysfunction.

PMID- 1386903
TI  - Immunization and vaccination protocol in hemodialysis patients with naturally
      acquired hepatitis B antibody.
AB  - Long-term behavior of naturally acquired anti-HBs antibody was tested every 6
      months for 3 years in 22 dialysis patients. Fifteen of them maintained protective
      levels throughout follow-up (102 and 85.5 mUI/ml at the beginning and the end,
      respectively). Seven of them became anti-HBs and were submitted to a 40
      micrograms booster injection of hepatitis B vaccine. Seroconversion was observed
      in 6 of 7 patients (85.7%) with a mean anti-HBs titer of 90.4 and 47.3 mUI/ml
      after 3 and 6 months, respectively. Protective anti-HBs level may be maintained
      longer in patients with natural immunity than in HBsAg-negative vaccinated
      subjects. Effectiveness of a reduced vaccination protocol in patients who have
      lost their natural immunization should be confirmed with further studies.

PMID- 1386904
TI  - Immunogenicity and efficacy of anti-hepatitis B vaccines in hemodialysis
      patients.
AB  - The 7-year follow-up with plasma-derived and 2-year follow-up with r-DNA vaccines
      have indicated the safety, immunogenicity and persistence of a vaccine-induced
      antibody response in hemodialysis patients. The results of our study indicate
      that these subjects have a lower and often inadequate immunogenic response to the
      HB vaccine and that the r-DNA vaccine gives a better seroconversion rate than the
      plasma-derived vaccines.

PMID- 1386905
TI  - Hepatitis B vaccination in uremic patients: comparison between recombinant and
      plasma-derived vaccine.
AB  - The immune response to recombinant and plasma-derived vaccines was evaluated in
      53 and 43 uremic patients, respectively. The total rate of seroconversion was
      around 80% with both vaccines, although a significantly higher response was
      obtained with the protocol using recombinant vaccine.

PMID- 1386906
TI  - Control of hepatitis B virus infection in dialysis units in Latium, Italy.
AB  - The prevalence of hepatitis B virus (HBV) markers was assessed in 1,841/2,178
      (84.5%) dialysis patients (DP) cared for in 38/47 dialysis units (80.9%) in
      Latium. Among DP, 205 (11.1%) were HBsAg positive: 13.8% of males and 7.1% of
      females (p less than 0.001); the prevalence increased with the length of time on
      dialysis (p for trend less than 0.001). No differences in HBV (HBsAg and/or anti
      HBc) distribution were seen related to age and sex. Of 664/1,539 vaccinated DP,
      150 (22.6%) were anti-HBc positive and 239 (36.0%) positive for anti-HBs alone.
      Of 875/1,539 nonvaccinated patients, 146 (16.7%) had no HBV marker. Vaccination
      against HBV did not influence the diffusion of HBV in our dialysis units and must
      be coupled with the implementation of long-standing infection control strategies.

PMID- 1386908
TI  - Immune response after vaccination with recombinant hepatitis surface antigen in
      maintenance hemodialysis patients and healthy controls.
AB  - We evaluated anti-HBs titers 2 months after vaccination with recombinant
      hepatitis surface antigen (rDNA-HBsAg) in 43 maintenance hemodialysis patients
      (MHP). Of these, 34 had not undergone hepatitis B virus vaccination previously
      (NV-MHP) and 9 had shown negative response to vaccination with plasma-derived
      HBsAg (HEVAC Pasteur; V-MHP). 120 healthy workers from the same hospital
      undergoing rDNA-HBsAg immunization were used as controls. All low responders (LR)
      (anti-HBs less than 100 mIU/ml) and nonresponders (NR; anti-HBs less than 10
      mIU/ml) were given a booster dose 3 months after the last dose of vaccine.
      Seroconversion rates were lower in NV-MHP (52.9%) than in controls (98.4%). V-MHP
      showed higher seroconversion rates (88.9%) than NV-MHP. In each group, the number
      of responders (R; anti-HBs greater than or equal to 100 mIU/ml), LR and NR was as
      follows: controls 101, 17, 2; NV-MHP 6, 12, 16; V-MHP 8, 0, 1. After booster
      dose, 17/17 controls LR and no NV-MHP LR showed a rise in anti-HBs titers over
      100 mIU/ml. Six months after the last dose of vaccine or the booster dose, anti
      HBs titer fell under 10 mIU/ml in 4/12 MHP LR and under 100 mIU/ml in 6/14 MHP R.
      To achieve high seroconversion rates and to avoid the decline of anti-HBs to
      nonprotective titers in MHP, a booster injection should be made at different
      dates after the first vaccination.

PMID- 1386907
TI  - A successful two-step integrated protocol of anti-HBV vaccination in chronic
      uremia.
AB  - A prospective study was performed in 40 chronic uremics which included: (1) the
      intramuscular administration to all patients of 40 micrograms of a DNA
      recombinant vaccine (Engerix-B) at 0, 1, 2, 6 months; (2) an intramuscular
      booster dose of 40 micrograms at 18 months in patients having an anti-HBs titer
      greater than 100 mIU/ml at the 7th month (group A); (3) a further intramuscular
      supplementary dose of 40 micrograms at 12 months (besides that at 18 months) in
      patients developing an antibody titer less than 100 mIU/ml at the 7th months
      (group B); (4) an intradermal course of 5 micrograms of vaccine every 2 weeks
      until the protective titer (greater than or equal to 10 mIU/ml) was achieved, and
      then every month for a total of 6 months in patients who did not develop a
      protective titer even after 19 months (group C). At the end of the study, all
      patients had developed a protective titer: 77.5% after the 4th intramuscular
      dose, 12.5% after the 5th and 10% after 3.5 +/- 0.5 (mean +/- SEM) intradermal
      inoculations. The mean antibody titers were 1,461 +/- 98 mIU/ml in group A, 594
      +/- 684 in group B and 131 +/- 133 in group C. In conclusion, our two-step
      integrated protocol gives an anti-HBs protective titer in all our patients.

PMID- 1386909
TI  - Immunogenicity of a recombinant hepatitis B vaccine in hemodialysis patients: a
      two-year follow-up.
AB  - The immunogenicity of a recombinant hepatitis B vaccine was evaluated in 35
      hemodialysis patients who received a standard dose (20 micrograms) of the vaccine
      at 0, 1, 2 and 6 months. After the full vaccination course (month 7), 60% (21/35)
      of the patients had seroconverted (anti-HBs titer greater than or equal to 10
      mIU/ml). The duration of protection lasted up to 18 months after the start of
      vaccination in 85.7% (18/21) of the responders. At that time, an additional dose
      was given to all the patients: 1-2 months later, the overall immunization rate
      had increased to 65.7% (23/35); lastly, in month 24 (i.e., 6 months after the
      booster dose), 62.5% (15/24) of the patients available for evaluation were still
      maintaining protective levels of anti-HBs antibodies. Comparable results had
      previously been obtained in 21 well-matched patients on our dialysis program who
      were vaccinated with a plasma-derived vaccine according to the recommended
      schedule.

PMID- 1386910
TI  - Use of immunomodulators (thymopentine) in hepatitis B vaccine in elderly patients
      undergoing chronic hemodialysis.
AB  - Thymopentine is a synthetic immunomodulator that positively affects T-lymphocyte
      maturation, reproduction and differentiation. In elderly uremic patients
      nonresponders to hepatitis B vaccine, the administration of this drug has been
      shown to improve the response to the new vaccination.

PMID- 1386911
TI  - Primary prevention: HBV vaccination in hemodialysis unit.
AB  - The authors evaluated the response rate to HBV vaccination in 27 dialyzed
      patients. In the 1st stage, the response was 70.37%; nonresponder patients (n =
      8) were treated with thymostimulin and revaccinated. The total percentage
      increased to 85.18%. In order to restore a normal response, the authors suggest
      to treat nonresponder patients with thymostimulin before revaccination.

PMID- 1386912
TI  - Evaluation of treatments for the vaccination against hepatitis B + thymopentine.
AB  - We have studied a series of 43 patients--who were suffering from uremia, subject
      to hemodialysis treatment, resulting seronegative to the test for HBV and who had
      never been vaccinated before--considering the HBS antibody as seroconversion
      index. We subdivided our patients into three groups, according to the treatment
      employed. First group: French vaccine; 2nd group: French vaccine+thymopenthine;
      3rd group: recombining DNA vaccine+thymopentine. From a statistical point of
      view, in the 3rd group we obtained a significant seroconversion in terms of
      patients, if compared with the other groups.

PMID- 1386913
TI  - Effect of dietary sodium on atrial natriuretic factor released in rats with
      chronic renal failure.
AB  - Studies were done in partially nephrectomized rats to examine the effect of
      dietary sodium intake on atrial natriuretic factor (ANF) released by the atria.
      Experiments were done in four groups of male Wistar rats. Group 1 (n = 10) and 3
      (m = 10) rats were sham-operated. Group 2 and 4 were 5/6 nephrectomized. Group 1
      and 2 were fed a sodium-supplemented diet. Group 3 and 4 received a sodium
      deficient diet. Renal functions were similar between group 2 and 4. Plasma ANF
      level was raised in group 2 (182 +/- 17 pg/ml). Circulating ANF levels in group
      1,3 and 4 were 95 +/- 5, 90 +/- 5 and 95 +/- 4 pg/ml, respectively. Atrial ANF
      contents were higher in partially nephrectomized rats after receiving a sodium
      supplemented diet. A reduction in atrial ANF contents occurred when fed a sodium
      deficient diet. In vitro studies were done to assess the rate of ANF released.
      ANF secretory rates were highest in group 2 (11 +/- 1.5 pg/min/mg). There was no
      difference between group 1,3 and 4. A positive correlation was found between
      plasma ANF and ANF released in all groups examined. Thus, plasma ANF levels were
      a good reflection of ANF secretory rates. A significant correlation existed
      between plasma ANF and sodium excretion in chronic renal failure rats (r = 0.78;
      p less than 0.01). A dissociation between plasma ANF and water excretion was
      seen. These results suggest that in chronic renal failure rats, ANF played a role
      in sodium adaptation.

PMID- 1386914
TI  - Involvement of 5-HT1, 5-HT2, and 5-HT3 receptors in the mediation of the
      prolactin response to serotonin and 5-hydroxytryptophan.
AB  - Serotonin (5-HT) is involved in the neuroendocrine regulation of prolactin (PRL)
      secretion as a stimulator. Within the last decade several 5-HT receptor types
      have been identified, but their individual role in the mediation of the PRL
      response to 5-HT is only partly understood. We investigated in conscious male
      rats the effect of different 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the
      PRL response to 5-HT or to the 5-HT precursor 5-hydroxytrytophan (5-HTP) which
      was administered in combination with the 5-HT reuptake inhibitor fluoxetine. 5-HT
      (0.5-5.0 mg/kg BW i.v.) or 5-HTP (25-100 mg/kg i.p.) in combination with saline
      or fluoxetine (10 mg/kg i.p.) increased the plasma PRL concentration dose
      dependently. Pretreatment with the 5-HT1+2 receptor antagonist methysergide (2.5
      mg/kg i.p.) prevented the stimulatory effect of 5-HT or 5-HTP + fluoxetine.
      Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (2.5
      mg/kg i.p.) inhibited the PRL response to 5-HT by approximately 80% and to 5-HTP
      + fluoxetine approximately 100%. A higher dose (10 mg/kg) of the 5-HT2 receptor
      antagonists possessed only 50% inhibitory effect. Pretreatment with the 5-HT3
      receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the
      PRL response induced by 5-HT or by 5-HTP + fluoxetine. The maximal inhibitory
      effect (approximately 80%) was obtained by a dose of 0.1 mg/kg of both
      compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1386915
TI  - Loss of the acoustic startle response following neurotoxic lesions of the caudal
      pontine reticular formation: possible role of giant neurons.
AB  - The effect of the excitotoxic N-methyl-D-aspartate agonist quinolinic acid in the
      caudal pontine reticular formation on the acoustic startle response was
      investigated in rats. Bilateral injections of 90 nmol of quinolinic acid led to
      large lesions in the reticular formation characterized by the loss of all neurons
      and a marked reduction or even abolition of the acoustic startle response; 18
      nmol of quinolinic acid led to smaller lesions characterized by a selective loss
      of giant neurons within the caudal pontine reticular formation and a reduction of
      the startle amplitude. The partial correlation analysis revealed that the
      reduction of the amplitude of the acoustic startle response can be correlated
      with the loss of the giant neurons (r = 0.575; d.f. = 29; P less than 0.001) but
      not with the reduction of the number of all neurons (r = 0.207; d.f. = 29; P
      greater than 0.2) in the caudal pontine reticular formation. These findings were
      reconciled with electrophysiological and anatomical data indicating that the
      giant neurons in the caudal pontine reticular formation receive acoustic input
      and project to motoneurons of the spinal cord. It is concluded that the caudal
      pontine reticular formation is an important element of the startle pathway and
      that the giant reticulospinal neurons constitute an important part of the
      sensorimotor interface mediating this response.

PMID- 1386916
TI  - Nerve growth factor selectively prevents excitotoxin induced degeneration of
      striatal cholinergic neurones.
AB  - Selective neuronal death is a prominent feature of human neurodegenerative
      disease both of genetic and idiopathic origin. Huntington's disease is
      characterised by the selective degeneration of striatal projection neurones, with
      the relative preservation of a variety of interneurones. The ability of the
      endogenous excitotoxin, quinolinic acid, to produce a pattern of selective
      neuronal cell death was investigated using immunocytochemical and histochemical
      techniques. We find that the large striatal, cholinergic interneurones are
      relatively spared, and that this sparing can be enhanced by the co-administration
      of the neurotrophin, nerve growth factor (NGF). Further, a single co-injection of
      NGF will selectively prevent both the cell death and morphological changes that
      occur within cholinergic cells when assessed 2 weeks later. These results suggest
      that an interaction between growth factors and excitotoxins can dramatically
      modify patterns of selective neuronal death.

PMID- 1386917
TI  - Intracerebroventricularly administered pertussis toxin blocks the central
      vasopressor action of neuropeptide Y(13-36) in the awake unrestrained male rat.
AB  - The effects of intracerebroventricular (i.v.t.) injections of pertussis toxin
      (PTX) (10 micrograms/30 microliters, 48 h) were studied on the cardiovascular
      actions of i.v.t. administered neuropeptide Y(13-36) (NPY(13-36)) as evaluated in
      the awake unrestrained male rat. The vasopressor action of NPY(13-36) in the peak
      dose of 3000 pmol per rat was significantly inhibited by pretreatment by PTX.
      Pertussis toxin treatment alone significantly reduced the baroreceptor reflex
      elicited by L-phenylephrine. The results are compatible with the view that G
      proteins mediate the central vasopressor actions of NPY(13-36) and thus probably
      are involved in NPY Y2-receptor transduction in cardiovascular areas of the
      brainstem.

PMID- 1386918
TI  - Eosinophilia-myalgia syndrome associated with ingestion of L-tryptophan.

PMID- 1386919
TI  - [Treatment of ectopic pregnancy by laparoscopy].
AB  - 12 ectopic pregnancy were operated by laparoscope. Earlier 2 patients had tubal
      pregnancy on the same side, and 3 had contralateral ectopic pregnancy. There were
      used aspiration method in 3 cases and salpingotomy + aspiration in 9 cases. The
      aspirated blood volume was 103.3 ml in average, the mean hospitalization time
      period were 3.1 days. The urinary HCG was negative after 1.9 days in average.
      There was neither early nor late operative complications. The authors suggest,
      that the introduction of the method has more advantages, when there are
      subjective and objective circumstances.

PMID- 1386921
TI  - Duodenal atresia: a source of small bowel obstruction in a 5-week-old infant.

PMID- 1386920
TI  - Ras controls coupling of growth factor receptors and protein kinase C in the
      membrane to Raf-1 and B-Raf protein serine kinases in the cytosol.
AB  - A dominant negative mutant of Ras, M17 Ras, was used to study the role of Ras in
      receptor coupling of Raf-1 and B-Raf protein serine/threonine kinases (PSKs). We
      found that mutant Ras blocks serum- and 12-O-tetradecanoyl phorbol 13-acetate
      induced activation of Raf-1 kinase in NIH3T3 cells and Raf-1 as well as B-Raf PSK
      stimulation by nerve growth factor (NGF) in PC12 pheochromocytoma cells. Mitogen
      stimulation of Raf kinase was measured by determination of Raf
      hyperphosphorylation and activity towards exogenous substrates and both of these
      events were inhibited in cells expressing M17 Ras. In contrast, tyrosine
      phosphorylation of a direct substrate of activated tyrosine kinase receptors,
      phospholipase C-gamma 1 (PLC-gamma 1), was unaffected. These data indicate that
      tyrosine phosphorylation of PLC-gamma 1 is not sufficient for growth induction in
      NIH3T3 cells and that Ras mediates signal transfer from activated membrane
      receptors to Raf kinases in the cytosol. As activated Raf induced differentiation
      in PC12 cells expressing M17 Ras we conclude that Raf kinase activation may be
      sufficient to account for this aspect of NGF function.

PMID- 1386922
TI  - Rorschach movement responses and the TAT Transcendence Index in physically
      handicapped children.
AB  - It has been supposed that those who give many Rorschach movement responses and
      score high on the TAT Transcendence Index are more inhibited in their motor
      activity. In previous studies motor inhibition was investigated by experimentally
      preventing motor activity. In the present study the effects of long-term motor
      inhibition on movement perception and fantasy level were explored in 19
      physically handicapped children, ages 11 to 15 years. Analysis showed that the
      physically handicapped children produced more (both human and animal) movement
      responses than the 19 normal children. Fantasy in the TAT was also higher in the
      former group. The theoretical basis of projective movement responses and fantasy
      in physical handicap needs more clarification. A more detailed approach in
      qualitative analysis of the movement responses is also important.

PMID- 1386923
TI  - The experiences of women pediatric dental residents: a survey.
AB  - A survey of 430 female pediatric dentists in the United States determined
      concerns and experiences they had during their advanced training programs. The
      return rate was 54%. Up to 83% (24) of the women who were pregnant during their
      residencies asked not to be exposed to certain environmental hazards during
      pregnancy and the postpartum period. They requested that program directors
      establish policies on known environmental hazards. Eighty-eight women (41%)
      commented that programs should offer flexible, preestablished and preannounced
      maternity leave policies. Survey respondents also expressed concerns about
      personal safety (5%), the lack of female role models (9%), and the need for more
      information on business management (30%). When the women were analyzed according
      to age, the following were significant (P less than .05): professional acceptance
      was of greatest concern to women ages 41-48; pregnancy and maternity leave, and
      balancing career with parenthood, significantly concerned women 25-32; and women
      ages 33-40 said business management was the issue causing the greatest
      frustration as a practicing pediatric dentist. While most respondents felt that
      they have the same professional opportunities as men, their greatest frustrations
      are a lack of acceptance by the professional and lay communities and trying to
      balance a career and motherhood.

PMID- 1386924
TI  - Attitudes of program directors toward women in pediatric dentistry training
      programs.
AB  - The number of women entering pediatric dentistry graduate programs is increasing.
      A formal survey was conducted in the fall of 1990 to determine what impact, if
      any, this increase is having on the programs. The survey sample consisted of the
      57 pediatric dentistry graduate program directors from the United States and
      Canada. The survey form included program data about gender distribution in the
      current and previous classes, and female faculty distribution within the
      programs. The survey requested information about the attitudes of various groups
      of individuals who interacted with the residents relative to the gender of the
      resident and again, relative to whether the resident was pregnant. Inquiry was
      made concerning maternity leave policies and selected treatment scenarios
      involving pregnant residents. Finally, questions were asked about motivational
      factors, personal priorities, and policy change for female vs. male residents.
      Fifty forms were returned for a return rate of 88%. The 48 forms analyzed
      revealed that 52% of current classes are female and 51% of applicants for 1991
      were female. Women comprise 23% of full-time and 26% of part-time faculty. There
      was no single issue perceived by program directors as a group to be a significant
      concern or problem relating to gender. Program directors would consider removing
      pregnant females from contact with combative patients (83%) and environmental
      hazards (85%), but fewer would consider removing them from contact with for HIV+
      or Hb+ patients.

PMID- 1386925
TI  - Opinions of pediatric dentists regarding their board certification process.
AB  - Despite frequently heard criticisms of the board certification process in
      pediatric dentistry, pediatric dentists have never been surveyed on this issue.
      To achieve a representative opinion, a formal survey was conducted during the
      summer and fall of 1990. The survey sample consisted of 300 practitioners
      selected randomly from the list of 4300 United States pediatric dentists. The
      survey form included demographic data, board status, general opinions about the
      process, and specific estimates of the reliability, validity, and utility of each
      of the five examination components. Comments were encouraged. A follow-up
      reminder was sent several weeks after the initial mailing. Ten forms were
      returned as undeliverable, reducing the sample to 290. In all, 150 forms were
      returned, for a return rate of 52%. One hundred and thirty-eight forms were
      completed and analyzed. This number included 54 pediatric Diplomates and 84
      nonboarded pediatric dentists. The Written and Oral sections generally were rated
      more favorably than the Case History, Site Visit, and Simulation sections.
      Nonboarded respondents were significantly more critical of the process on every
      item, without exception. All differences exceeded the 0.01 level.

PMID- 1386926
TI  - Gender differences in student withdrawals from postdoctoral programs of pediatric
      dentistry: 1986-1990.

PMID- 1386927
TI  - Survey of pediatric dentists, 1991: a preliminary report on demographics and
      opinions.

PMID- 1386929
TI  - Atrial natriuretic factor: lack of effect on ATPase activity of human erythrocyte
      membranes.

PMID- 1386930
TI  - Effect of 5-hydroxytryptophan [5-HTP) on sleep in parachlorophenylalanine (PCPA)
      pretreated birds.

PMID- 1386928
TI  - A carboxyl-terminal-domain kinase associated with RNA polymerase II transcription
      factor delta from rat liver.
AB  - We previously purified RNA polymerase II transcription factor delta from rat
      liver and found that it has an associated DNA-dependent ATPase (dATPase)
      activity. In this report, we show that delta is also closely associated with a
      protein kinase activity that catalyzes phosphorylation of the largest subunit of
      RNA polymerase II. Kinase activity copurifies with transcription and DNA
      dependent ATPase (dATPase) activities when delta is analyzed by anion- and cation
      exchange HPLC as well as by sucrose gradient sedimentation, arguing that delta
      possesses all three activities. Phosphorylation of the largest subunits of both
      rat and yeast RNA polymerase II is stimulated by DNA, whereas phosphorylation of
      a synthetic peptide containing multiple copies of the carboxyl-terminal
      heptapeptide repeat is not. Although both ATP and GTP appear to function as
      phosphate donors, GTP is utilized less than 10% as well as ATP. These findings
      suggest that delta may exert its action in transcription at least in part through
      a mechanism involving phosphorylation of the largest subunit of RNA polymerase
      II.

PMID- 1386931
TI  - Developmental changes in the fatty acids of rat uterus and the influence of
      dietary essential fatty acids.
AB  - The effect of age on uterine fatty acid composition was studied in rats fed diets
      of differing fatty acid composition. Uteri of newly weaned 23-day rats had a
      higher fatty acid content and a higher proportion of short-chain (less than or
      equal to C18) fatty acids. Higher incorporation of C less than or equal to 18
      fatty acids into neutral lipid (NL) and phospholipid (PL) of young 42-day rats
      compared with adult 240-day rats was detected. Uterine NL incorporated
      predominantly C less than or equal to 18 fatty acids which may be an important
      metabolic energy store in developing uterine tissue. Incorporation of C less than
      or equal to 18 fatty acids by uterine PL and NL was relatively unselective. In
      contrast, there was selective retention of arachidonic acid (AA) and
      docosahexanoic acid (DHA) throughout uterine development. An effect of dietary
      EFA on uterine n-3 and n-6 EFA was detected in each age group. There was marked
      retention of uterine AA when dietary supplies of n-6 EFA were low, but the total
      AA, eicosapentaenoic acid (EPA) and DHA in uterine PL remained constant in the
      three diet groups, and a constant content of AA, EPA and DHA was maintained
      throughout uterine development, regardless of diet. The degree of n-3
      substitution achieved in this study inhibited uterine release of PG and
      parturition in adult rats.

PMID- 1386932
TI  - Mechanisms of cell killing in photodynamic therapy using a novel in vivo drug/in
      vitro light culture system.
AB  - Photodynamic therapy of certain neoplasms has emerged as a promising form of
      cancer treatment. This type of therapy involves the exogenous administration of a
      photosensitizer with subsequent exposure to light. The ensuing photochemical
      reaction results in destruction of the tumor. Whether tumor cells are destroyed
      directly by the photodynamic treatment or indirectly as a result of destruction
      of the tumor microvascular bed is unknown. To address this question, methods were
      adapted to test whether combinations of a photosensitizer and light resulted in
      direct cell killing of precision cut tissue slices placed in culture. The major
      advantages of this culture system are that photosensitizers are administered in
      vivo, tissue slices produced in minutes, placed in culture medium, and irradiated
      in vitro. Any resulting cellular destruction occurs in the absence of a
      functioning vascular system and indicates that photodynamic therapy acts through
      a direct cell killing mechanism. Tissue slice viability was monitored by two
      standard methods: assay for intracellular potassium and morphological examination
      at the electron microscopic level. The effects of hematoporphyrin derivative and
      light were examined on tissue slices produced from a prostate adenocarcinoma
      transplanted into male Copenhagen rats. The data indicate that direct killing of
      tumor slices occurs and is dependent on the irradiation protocol used.

PMID- 1386933
TI  - Tumoricidal capacities of macrophages photodynamically activated with
      hematoporphyrin derivative.
AB  - Four days after administration to mice of small amounts (30-600 ng/mouse) of
      hematoporphyrin derivative (HPD), peritoneal macrophages exhibited a greatly
      enhanced Fc-receptor mediated phagocytic capacity as assayed by ingestion
      activity of IgG-coated sheep erythrocytes. Much higher doses (greater than 3000
      ng/mouse) did not have this effect. The peritoneal macrophages activated by
      administration of HPD have tumoricidal capacity for IgG-coated retinoblastoma
      cells. We then studied in vitro photodynamic activation of macrophages by white
      and red fluorescent light irradiation of mouse peritoneal cells (mixture of
      macrophages and B and T lymphocytes) in media containing very low concentrations
      of HPD. A short (5 s) white fluorescent light exposure (1Wm-2) of peritoneal
      cells in a medium containing 0.03 ng HPD/mL produced the maximal level of
      ingestion activity of macrophages. A 15 s red fluorescent light exposure (1Wm-2)
      of peritoneal cells in a medium containing 0.1 ng HPD/mL produced the maximal
      level of ingestion activity of macrophages. Thus, photodynamic activation of
      macrophages with white fluorescent light is more efficient than that with red
      fluorescent light. This can be explained by the fact that HPD has a large
      absorption peak at about 364 nm which extends into the visible range, and
      decreasingly smaller absorption bands at 500, 535, 570 and 630 nm. In vitro
      photodynamically activated macrophages showed efficient tumoricidal activity
      regardless of the type (white or red) of light used. These results suggest that a
      low level of HPD promotes therapeutic immunopotentiation.

PMID- 1386934
TI  - Effect of warm air on the shear bond strength of composite resins.
AB  - This investigation evaluated the operating characteristics of a recently
      introduced tooth dryer and its effect on the bond strength of three composite
      resins to etched enamel. The effect of varying air pressure, distance from the
      tip of the tooth dryer, and distance laterally from mid-air stream on temperature
      were measured using a rapid-response thermocouple. Specimens were subjected to
      shear forces either immediately after bonding or after 5 days of water storage.
      The air stream required from 32 to 41 seconds to reach maximal temperature;
      however, more than 90% of the maximal temperature was obtained in 20 seconds.
      There was an increase in temperature with increased air pressure and a decrease
      in temperature with increasing distance from the tip. The temperature dropped
      rapidly laterally from the center of the air stream. The shear bond strength
      measurements were significantly higher for the specimens prepared using the tooth
      dryer for one composite resin tested immediately after bonding; there was no
      statistically significant difference for the other resins. The effect of warm air
      on the shear bond strength of composite resins to etched enamel may be dependent
      on the resin used and the time between bonding and testing.

PMID- 1386935
TI  - [Role of percutaneous angioplasty in keeping vascular access for hemodialysis].
AB  - The stenoses of anastomosed vessels or of implantation grafts are among the most
      frequent causes of insufficiency of vascular hemodialysis accesses. Percutaneous
      angioplasty allows the interventional radiologist too to participate in the
      salvage of shunts. From 1985 to 1991, 46 patients underwent the procedure.
      Angioplasty could be performed in 43 of them, and had to be repeated in some
      cases because of either relapse or malfunctioning new vascular access. On the
      whole, 59 maneuvers were performed, and 96 stenoses treated, 71 in Brescia-Cimino
      fistulas and 25 in Gore-Tex prostheses. The optimized standard technique employs
      access through the efferent vein and a diagnostic evaluation after blocking the
      flow with an inflatable cuff; 2-3 distensions lasting 2-3 minutes are performed
      with a 3.5-4 mm x 20 mm balloon catheter for the anastomosis. One or more 15-20
      minute distensions follow, with a 6-8 mm x 20-40 mm Zijlstra balloon catheter
      (Schneider) for the lesions in the efferent vein. Our initial success rate was
      88.7% (55 of 62 procedures). Follow-up results at 3, 6, 12, 24 months proved that
      for this type of lesion, which is usually supported by fibrosis and endarterial
      hyperplasia, estimated relapse rates exceed 50% in the first year and are lower
      than 10% a year in the following years. Complications are quite rare and can be
      partly prevented if the correct indications are followed, overdistension is
      avoided and the proper material is used. On account of the good results it
      yields, of its relative simplicity and of the very low incidence of
      complications, angioplasty should be considered as the treatment of choice for
      stenoses and their relapses in vascular hemodialysis accesses. As for treatment
      protocol, angioplasty is not a procedure to occasionally replace surgery, but a
      therapeutic approach which can be repeated at regular time intervals and can
      prolong the life of hemodialysis fistulas, thus delaying surgical reconstruction.

PMID- 1386936
TI  - [Focal infections caused by non-typhi Salmonella: a review of our case series and
      comparison with other series].
AB  - Nine cases of local infection due to non typhi Salmonella enterica, some of them
      of unusual localization, in 8 patients (mean age 64.9 +/- 12.4 years) attended in
      Zamora's Virgen de la Concha Hospital over a period of five years, are described.
      Focal salmonellosis represented 1.5% of non-typhi salmonellosis cases in that
      period (9 out of 606 detected cases). 6 of the 8 patients (75%) showed a
      predisposing disease. In two patients the previous existence of gastroenteritis
      due to Salmonella was assessed and only in one of them concomitant bacteremia was
      detected. Soft-tissue infections were the more frequent clinical feature: plantar
      abscess, two abdominal wall abscesses--one of them after cholecystectomy--post
      pericardiotomy thoracic wall abscess and perianal abscess. Three soft-tissue
      infections were due to group B serotypes. 4 out of five soft-tissue infections
      evolved favorably with surgical treatment. The rest of the series is formed by
      two cases with acute cholecystitis in patients with previous cholelithiasis (one
      of whom relapsed originating an abdominal wall abscess), a recurrent pleural
      empyema and a purulent pericarditis. The pericarditis was produced by S.
      enteritidis. Patient showed signs of cardiac tamponade, his condition improving
      after pericardial drainage and parenteral and intrapericardial administration of
      ciprofloxacin. Epidemiologic and clinic characteristic of our series are compared
      with other series of focal salmonellosis.

PMID- 1386937
TI  - Co-expression of T-cell receptor beta and delta mRNA detected at high frequency
      in hybridomas derived from adult thymus.
AB  - Two different hybridoma collections from adult C3H/HeJ thymus were generated in
      order to analyse T-cell receptor (TcR) rearrangements, surface expression of T
      cell receptors and differentiation markers as well as lymphokine production.
      Large, low density thymocytes were either directly fused to the thymoma BW 5147
      alpha-beta- variant, or fused after stimulation with Concanavalin A in the
      presence of interleukin-2 for 48 h. The hybrids obtained from Concanavalin A
      stimulated cells represented rather mature thymocytes, with regard to TcR
      rearrangements and surface T-cell receptor expression. The collection of hybrids
      derived from freshly isolated large thymocytes contained cells in various stages
      of T-cell development. An unexpectedly large number of hybrids (46 out of 84)
      from this group expressed full-length C beta together with full-length, or
      shorter, C delta mRNA. This finding suggests that a considerable proportion of
      alpha beta T cells proceeds through a stage in development where delta genes are
      being rearranged and transcribed.

PMID- 1386938
TI  - Cytoplasmic calcium fluxes induced in cytotoxic effector cells by engagement of
      Fc gamma receptors I, II, and III.
AB  - Changes in the intracellular calcium ion concentration ([Ca2+]i) of monocytes,
      granulocytes, and NK cells have been studied following either (1) independent
      cross-linking of Fc gamma receptors (Fc gamma R) I, II, or III, with F(ab
      gamma')2 fragments of monoclonal antibodies; or (2) linking of a selected Fc
      gamma R to a tumour cell target with bispecific F(ab' gamma)2 antibodies. Upon
      cross-linking each Fc gamma R with antibody an increase in the [Ca2+]i was
      observed, although all receptors apart from Fc gamma RIII on NK cells required
      additional cross-linking with an anti-mouse Fab' gamma. These results indicate
      that each type of receptor can transduce signals to the cell independently.
      Bispecific antibodies (anti-Fc gamma R x anti-target) linking cytotoxic Fc gamma
      R-bearing effector cells to tumour target cells also mediated increases in
      [Ca2+]i for all Fc gamma R tested except for Fc gamma RIII on granulocytes. The
      failure to transduce a signal via this receptor may be related to the GPI link,
      which is in contrast to the transmembrane link of Fc gamma RIII on NK cells.
      Significant lysis of tumour cell targets occurred when bispecific antibodies
      recruited NK cells or monocytes, but not granulocytes, via Fc gamma R. Chelation
      of intracellular Ca2+ in the effector cells reduced the observed lysis,
      suggesting a role for Ca2+ in the pathways leading to cytotoxicity.

PMID- 1386939
TI  - Identification of human T cells that require zinc for growth.
AB  - Zinc is an essential trace element required for normal function of the immune
      system. Deficiency of zinc results in marked thymic atrophy in experimental
      animals, and in man immunodeficiency is a recognized complication of zinc
      deprivation. Although numerous proteins require zinc as a cofactor, its precise
      functions in the immune system remain unknown. The mechanism by which metals
      stimulate lymphocytes, whether all T cells are responsive, and the relationship
      to zinc requirements have not been determined. We unexpectedly isolated a number
      of human T-cell lines that have a highly specific requirement for zinc. The
      ability to respond to zinc resides in only a subset of T cells since antigen
      specific clones are not stimulated by zinc. Although proliferation requires the
      presence of antigen-presenting cells and is restricted by class II MHC antigens,
      antigen-presenting cells could not be pulsed with zinc to induce T-cell
      activation. Our results suggest that zinc-dependent T cells are a subset of CD4+
      cells present in all normal individuals and that zinc stimulates their growth by
      novel mechanisms.

PMID- 1386940
TI  - Coding region polymorphisms of human T-cell receptor V beta 6.9 and V beta 21.4.
AB  - Two new TCRV beta coding region polymorphisms were identified: V beta 6.9a/b and
      V beta 21.4a/b. In both cases, a single nucleotide difference gives rise to an
      amino acid exchange. Genomic typing by the PCR/sequence-specific oligonucleotide
      probing technique was performed to study a possible contribution of these two new
      polymorphisms in susceptibility to autoimmune diseases. However, there was no
      association with insulin-dependent diabetes mellitus, rheumatoid arthritis,
      juvenile rheumatoid arthritis, multiple sclerosis, myasthenia gravis or coeliac
      disease. On the other hand, significant differences were found between Caucasoid
      and Oriental populations in frequencies of the V beta 6.9 and V beta 21.4
      alleles.

PMID- 1386941
TI  - Splicing takes a holliday.

PMID- 1386942
TI  - Computerized tomography in persons with Down syndrome and atlantoaxial
      instability.
AB  - Atlantoaxial instability has been reported to occur in 9-31% of persons with Down
      syndrome. The authors studied a subsample of patients with this chromosomal
      disorder who had both routine roentgenograms and computerized tomographic
      examinations. Computerized tomography revealed numerous skeletal anomalies of the
      C1-C2 region as well as spinal cord compression that were not visualized on plain
      roentgenograms. In addition, an apparent discrepancy of the atlanto-dens interval
      measurements between the two procedures was noted. The measurements of the plain
      roentgenograms were significantly greater than those obtained by computerized
      tomography, which is due to the magnification factor in plain roentgenograms.

PMID- 1386943
TI  - Use of the International Classification of Diseases (ICD-9-CM) to identify
      hospitalizations for mechanical low back problems in administrative databases.
AB  - Large administrative databases are increasingly valuable tools for health care
      research. Although increased access to these databases provides valuable
      opportunities to study health care utilization, costs and outcomes and valid and
      comparable results require explicit and consistent analytic methods. Algorithms
      for identifying surgical and nonsurgical hospitalizations for "mechanical" low
      back problems in automated databases are described. Sixty-six ICD-9-CM diagnosis
      and 15 procedure codes that could be applied to patients with mechanical low back
      problems were identified. Twenty-seven diagnosis and two procedure codes identify
      hospitalizations for problems definitely in the lumbar or lumbosacral region.
      Exclusion criteria were developed to eliminate nonmechanical causes of low back
      pain, such as malignancies, infections, and major trauma. The use of the
      algorithms is illustrated using national hospital discharge data.

PMID- 1386944
TI  - A new paradiscal injection technique for the relief of back spasm after
      chemonucleolysis.

PMID- 1386945
TI  - Laparoscopic cholecystectomy during pregnancy.
AB  - There is a strong association between pregnancy and gallstones. When acute
      cholecystitis or recurring bouts of biliary colic occur during pregnancy, medical
      therapy is usually initiated but occasionally fails. Laparoscopic cholecystectomy
      has recently been described for the treatment of symptomatic cholelithiasis, but
      many authors consider pregnancy to be an absolute contraindication to this
      operation. We herein describe the management of markedly symptomatic
      cholelithiasis during the second trimester of pregnancy using laparoscopic
      techniques in five patients. Tocolytic medications were administered
      perioperatively in two patients, and open laparoscopy or the use of an
      alternative site for insertion of the initial port was used in all patients.
      Laparoscopic cholecystectomy without cholangiograms was successful in all five
      patients and postoperative hospitalization ranged from 24 to 48 h. Uncomplicated
      term delivery has occurred in three of the five patients; in the other two
      patients, normal pregnancies are continuing. Laparoscopic cholecystectomy can be
      performed safely during pregnancy, as long as the patient is monitored carefully
      and specific precautions are observed.

PMID- 1386947
TI  - A newly designed single dissector useful for laparoscopic cholecystectomy.
AB  - We developed a modified dissector capable of carrying out a one-hand operation
      involving three fundamental functions: grasping, sharp or blunt dissection, and
      dividing the tissues. With this single dissector, laparoscopic cholecystectomy
      can be rapidly and safely performed without changing the forceps or instruments
      through the trocar.

PMID- 1386946
TI  - Techniques for laparoscopic cholangiography and removal of common duct stones.
AB  - As laparoscopic cholecystectomy becomes more prevalent, the unexpected finding of
      common duct stones by operative cholangiography presents a therapeutic dilemma
      for the surgeon. We present our current techniques for laparoscopic
      cholangiography and management of choledocholithiasis, including the use of
      angioplasty balloons for ampullary dilation.

PMID- 1386948
TI  - Totally intra-abdominal laparoscopic Billroth II gastrectomy.

PMID- 1386949
TI  - Calphobindin I (annexin V) inhibits protein kinase C.
AB  - We investigated the inhibitory effect of calphobindin I (CPB I) on protein kinase
      C activity. CPB I inhibited protein kinase C activity in a concentration
      dependent manner with an IC50 value of 70 nM. The inhibition of protein kinase C
      by CPB I was Ca(2+)-dependent, and was partially overcome by increasing the
      concentration of phosphatidylserine. Since CPB I is widely distributed in various
      organs and cells, it is presumed that CPB I is an endogenous inhibitor of protein
      kinase C.

PMID- 1386950
TI  - Toxicological investigations in the semiconductor industry: I. Studies on the
      acute oral toxicity of a complex mixture of waste products from the aluminium
      plasma etching process.
AB  - In dry etching processes--one of the sources of potential exposure to toxic
      wastes in the semiconductor industry--complex mixtures of inorganic and organic
      compounds arise from reactions between feed stock gases (BCl3/Cl2), top layers
      (aluminium photoresist), and the carrier gas (N2). Two different fractions of the
      complex mixture--one an ethanolic solution (ES) and the other an insoluble liquid
      residue (LR)--were examined for acute oral toxicity in rats. Analytical data
      showed that the ethanol soluble fraction contained mainly inorganic compounds,
      whereas the residue contained various halogenated hydrocarbons. Neither death nor
      behavioral changes occurred after oral administration and observation up to 23
      days. ES caused a lower mean arterial blood pressure in both sexes, increased P-R
      intervals in male rats, and caused some mild biochemical and hematological
      alterations and changes in relative organ weights compared to the control groups.
      Exposure to LR influenced food and water intake, and caused a significant
      decrease in body weights, signs of polyurie, as well as changes in various
      relative organ weights and biochemical and hematological parameters. The blood
      pressure of the male animals fell and the heart rates of both sexes decreased.

PMID- 1386951
TI  - Laparoscopic occlusion of testicular veins for clinical varicocele.
AB  - Surgery via the laparoscope is now a reliable and cost-effective alternative to
      some open surgical procedures. Advances in videoendoscopy, incorporating optical
      magnification combined with the development of instruments with which to dissect,
      ligate, and transect blood vessels provide the urologist the opportunity to
      surgically correct a varicocele. In the outpatient setting, 4 patients (14-26
      years of age) underwent laparoscopic ligation of the left internal spermatic
      veins for painful left varicocele. Carbon dioxide pneumoperitoneum was obtained
      using a Veress needle. A 10-mm laparoscope was placed intraperitoneally through a
      cannula inserted in the infraumbilical border. Utilizing two additional
      endosurgical ports (5 mm and 10 mm) through which 5-mm dissecting instruments and
      vaso-occlusive endoclips were placed, three veins were individually isolated and
      ligated in each of the 4 patients. In all 4 patients, the left testicular artery
      was visualized and preserved. There was no blood loss or other intraoperative
      complication. In each patient the varicocele was successfully corrected.
      Analgesic medication was not required postoperatively. We conclude that
      laparoscopic ligation of the internal spermatic veins is a safe and effective way
      of treating a varicocele without immediate postoperative sequelae. Long-term
      follow-up is necessary to determine the place of the endoscopic approach.

PMID- 1386952
TI  - The efficacy of moxidectin against Dictyocaulus viviparus in cattle.
AB  - The efficacy of an injectable and a pour-on formulation of moxidectin against
      Dictyocaulus viviparus in cattle was examined. The results show that both
      formulations have an efficacy of 100% against adult worms and developing and
      inhibited larval stages of D. viviparus.

PMID- 1386953
TI  - The absorbance spectrum and photosensitivity of a new synthetic "visual pigment"
      based on 4-hydroxyretinal.
AB  - The firefly squid, Watasenia scintillans, is the only animal known to possess a
      visual pigment in which the chromophore is 4-hydroxyretinal. This paper describes
      the absorbance spectrum and some properties of a synthetic "A4" visual pigment
      generated from bovine opsin and 4-hydroxyretinal. The absorbance spectrum of this
      pigment is compared with (a) bovine rhodopsin and (b) a rhodopsin template with
      the same lambda max as the synthetic visual pigment. The A4 pigment is shown to
      have an absorbance spectrum that is almost identical to that of a rhodopsin
      template. It is also shown that the photosensitivity and thermal stability of the
      A4 pigment, dispersed in detergent micelles, is essentially similar to that of
      rhodopsin.

PMID- 1386955
TI  - Intracellular actions of gonadotropic and peptide hormones and the therapeutic
      value of GnRH-agonists in ovarian cancer.
AB  - During the last two decades, considerable experimental evidence has been
      collected indicating that epithelial ovarian cancer might be gonadotropin
      dependent. LH and FSH receptors have been described in some of these tumors. The
      proliferation of ovarian cancer cells could be stimulated in vitro by
      gonadotropins. Suppression of endogenous LH and FSH secretion by GnRH-agonist
      treatment inhibited the growth of experimental or heterotransplanted ovarian
      cancers in various animal models. A number of recent phase II clinical trials
      have shown that the application of GnRH-agonists can lead to remission or stable
      disease in patients with relapsed advanced ovarian cancer. At present,
      prospective controlled clinical studies are being performed to assess the
      efficacy of GnRH-agonist treatment in addition to conventional surgical and
      cytostatic therapy in ovarian cancer in FIGO stages III and IV. Also, direct
      effects of GnRH analogues on ovarian cancer seem possible: a GnRH-like protein
      has been found in the human ovary. Our group discovered and partially
      characterized a specific GnRH-binding site (mol. wt 63.2 kDa) in ovarian cancer
      which is very similar to other human extrapituitary GnRH-binding sites of the low
      affinity, high capacity type, e.g. in breast cancer or the placenta. Recently,
      other groups have described also high affinity GnRH-agonist binding sites in
      ovarian cancer as well as in other extrapituitary tissues. First results from our
      laboratory indicate that the proliferation of certain ovarian cancer cell lines
      in vitro is reduced by both agonistic and antagonistic analogues of GnRH. Other
      authors were able to inhibit gonadotropin-induced in vitro proliferation of
      ovarian cancer cell lines by co-incubation with a GnRH-agonist.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1386954
TI  - Cellular response and anti-HBs synthesis in vitro after vaccination with yeast
      derived recombinant hepatitis vaccine.
AB  - Two groups of subjects receiving two different doses of yeast-derived recombinant
      hepatitis B surface antigen (rHBsAg) (10 micrograms Gen-HB-Vax, Merck Sharp and
      Dohme and 20 micrograms Engerix-B, Smith Kline and French) were investigated for
      in vitro specific humoral and cellular response to the native protein. In vitro
      proliferative response was dependent on the following critical variables: (1)
      antigen-specific precursor lymphocytes were present in the peripheral blood for a
      very short time; (2) the number of circulating specific precursors was dependent
      on the dose of HBsAg used for vaccination; (3) the presence of antigen-presenting
      cells was necessary to obtain a blastogenic response in vitro. In vitro
      proliferation was enhanced by the addition of recombinant interleukin 2 (rIL-2).
      Spontaneous and stimulated (anti-CD3, pokeweed mitogen) anti-HBs antibody
      production in vitro was obtained in only eight out of 20 subjects after the
      fourth boost. Although a different immunogenicity of the two vaccines cannot be
      excluded, these data strongly suggest that T and B cells responsive to HBsAg
      present different kinetics of recirculation in the peripheral blood, depending on
      the antigen dose used for immunization.

PMID- 1386956
TI  - Is 3 alpha, 17 beta-androstanediol-glucuronide a diagnostic marker in women with
      androgenic manifestations?
AB  - 3 alpha, 17 beta-androstanediol-glucuronide (Adiol-G) has been described as a
      marker of local androgen excess due to the increased activity of 5 alpha
      reductase in the cells of the hair follicles. In order to test the diagnostic
      value of Adiol-G, the serum level was compared to that of testosterone, free
      testosterone, dehydroepiandrosterone sulfate (DHEA-S), androstenedione and to the
      body mass index in 44 women with androgenic symptoms (Group I), 27 women with
      menstrual disturbances but no androgenic symptoms (Group II), and 48 healthy
      women (Group III) who served as controls. Adiol-G was significantly higher (7.8
      +/- 5.1 nmol/l) in women with androgenic symptoms than in the other groups, but
      there was a considerable overlap. Serum testosterone was also found to be higher
      in Group I than in Groups II and III, respectively. There was a significant
      correlation between Adiol-G and testosterone, and Adiol-G and DHEA-S. No
      significant correlation could be shown to exist between androstenedione and Adiol
      G. When Adiol-G and testosterone were simply classified as 'normal' or
      'increased' (Adiol-G 9.4 nmol/l; testosterone greater than 2.4 nmol/l), higher
      than normal values of the former were found in the presence of normal
      testosterone in only 4% of the cases. It is concluded that the level of Adiol-G
      generally parallels that of testosterone. Consequently, it does not seem to be an
      effective marker of peripheral androgen excess.

PMID- 1386957
TI  - [Renal artery angioplasty].
AB  - In the 59 hypertensive patients submitted to percutaneous transluminal
      angioplasty (PTA) of the renal artery, there was an immediate success in the
      blood pressure in 91.5% and a later one of 79.6%. In these patients we obtained
      better results: 81.4% in the unilateral lesions, more than in the bilateral ones-
      72.7%; 82.5% in the renal artery trunk lesions, more than in the ostium ones-
      71.4%; 88.9% in the lesions of fibromuscular origin, more than in the
      aterosclerotic ones--75%; 84.4% in up to 55 years old patients, more than in
      older ones--71.4%. These differences were not significant. The results of renal
      angioplasty in renovascular hypertension suggest this type of intervention as an
      alternative treatment.

PMID- 1386958
TI  - [Functional and anatomic involvement of the right ventricle in arterial
      hypertension].
AB  - The early cardiac involvement is well known in arterial hypertension, particulary
      the diastolic and left ventricular hypertrophy. The right ventricle and pulmonary
      circulation may likewise be affected early in the course of disease. Scarce
      though it is, studies on the right repercussion of hypertension have shown an
      increase in pulmonary resistance and right-sided pressures in hypertensive
      patients. In spite of the limitations arising from the complex geometry of the
      right ventricule, echocardiography may be the most important non-invasive
      technique in the evaluation of the structural and functional repercussion of
      hypertension on the right ventricle. Our studies have revealed an increase in the
      diastolic thickness of the right ventricular free wall in hypertensive patients,
      as well as a good correlation between the diastolic thickness of the free walls
      of both ventricles. Most studies suggest a functional relationship between both
      ventricles. Structural alterations may occur in the right ventricle, along with
      hemodynamic alterations, thus suggesting structural and functional similarity of
      both ventricles, regarding cardiac response to arterial hypertension.

PMID- 1386959
TI  - [Precocity of diastolic dysfunction in hypertensive cardiopathy].
AB  - Left ventricular hypertrophy (LVH) is a well defined cardiovascular risk factor
      and is frequently detected by echocardiography in hypertensive patients. Systolic
      cardiac function at rest is usually preserved in hypertension, however, diastolic
      function may be frequently altered. Evidence for these changes has been
      demonstrated by Echo-Doppler even without concomitant existence of LVH.
      Quantitative and qualitative changes in contractile proteins and interstitial
      tissue as well as reduction of coronary reserve may be related to the mentioned
      dysfunction. Recent studies have confirmed the precocity of diastolic dysfunction
      both in laboratory animals as well as man. Further significant differences have
      been shown between normotensives with and without a family history of systemic
      hypertension. The relative importance of diastolic disfunction is also related to
      its possible role in the genesis of cardiac failure and its probable role in the
      modulation of cardiopulmonary reflexes in addition to the hemodynamics of
      arterial hypertension. It is not yet known if the presence of diastolic
      dysfunction is a mechanism or a risk marker like LVH.

PMID- 1386960
TI  - [Percutaneous transluminal angioplasty in occlusive renal disease --alternative
      to surgery?].

PMID- 1386961
TI  - [The heart and arterial hypertension].

PMID- 1386962
TI  - The development of functionally responsive T cells.
AB  - The work reviewed in this article separates T cell development into four phases.
      First is an expansion phase prior to TCR rearrangement, which appears to be
      correlated with programming of at least some response genes for inducibility.
      This phase can occur to some extent outside of the thymus. However, the profound
      T cell deficit of nude mice indicates that the thymus is by far the most potent
      site for inducing the expansion per se, even if other sites can induce some
      response acquisition. Second is a controlled phase of TCR gene rearrangement. The
      details of the regulatory mechanism that selects particular loci for
      rearrangement are still not known. It seems that the rearrangement of the TCR
      gamma loci in the gamma delta lineage may not always take place at a
      developmental stage strictly equivalent to the rearrangement of TCR beta in the
      alpha beta lineage, and it is not clear just how early the two lineages diverge.
      In the TCR alpha beta lineage, however, the final gene rearrangement events are
      accompanied by rapid proliferation and an interruption in cellular response gene
      inducibility. The loss of conventional responsiveness is probably caused by
      alterations at the level of signaling, and may be a manifestation of the
      physiological state that is a precondition for selection. Third is the complex
      process of selection. Whereas peripheral T cells can undergo forms of positive
      selection (by antigen-driven clonal expansion) and negative selection (by
      abortive stimulation leading to anergy or death), neither is exactly the same
      phenomenon that occurs in the thymic cortex. Negative selection in the cortex
      appears to be a suicidal inversion of antigen responsiveness: instead of turning
      on IL-2 expression, the activated cell destroys its own chromatin. The genes that
      need to be induced for this response are not yet identified, but it is
      unquestionably a form of activation. It is interesting that in humans and rats,
      cortical thymocytes undergoing negative selection can still induce IL-2R alpha
      expression and even be rescued in vitro, if exogenous IL-2 is provided. Perhaps
      murine thymocytes are denied this form of rescue because they shut off IL-2R beta
      chain expression at an earlier stage or because they may be uncommonly Bcl-2
      deficient (cf. Sentman et al., 1991; Strasser et al., 1991). Even so, medullary
      thymocytes remain at least partially susceptible to negative selection even as
      they continue to mature.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1386963
TI  - [Delayed treatment with dextromethorphan can reduce ischemic retinal damage in
      rabbit].
AB  - Previous studies have suggested that prophylactic treatment by dextromethorphan
      (DEX), N-methyl-D-aspartate (NMDA) receptor antagonist can protect the retina
      against ischemia. To investigate the effect of DEX on the proceeding ischemic
      retina, 0.1% DEX hydrobromide was intravenously administered in rabbits
      immediately (group A), 1 hour (group B) or 2 hours (group C) after the release
      from ischemia induced by increasing intraocular pressure to 130 mmHg for 90 min.
      Normal saline was infused immediately after the release from ischemia as control
      rabbits. Retinal function was monitored by recording electroretinogram (ERG).
      Twenty four hours after the release of ischemia, the recovery rates of ERG.b-wave
      amplitudes in groups A, B and C were 61.3 +/- 3.3, 52.2 +/- 9.0 and 43.6 +/- 8.4%
      of the preischemic amplitude, respectively. The recovery rate of the group A was
      higher than that of the control (41.9 +/- 10.6%), while no significant
      differences were seen between groups B or C and the control. The results suggest
      that DEX can protect the retina if it is administered immediately after the
      release of ischemia.

PMID- 1386964
TI  - Revising axis V for DSM-IV: a review of measures of social functioning.
AB  - OBJECTIVE: Axis V, which uses the Global Assessment of Functioning Scale in the
      multiaxial system of DSM-III-R, is under review for DSM-IV. This article examines
      what is known about axis V and selectively reviews the literature on measures of
      social functioning to identify potential alternatives to the Global Assessment of
      Functioning Scale. METHOD: About 25 studies on the use, reliability, and validity
      of axis V in DSM-III and DSM-III-R are reviewed. In addition, nearly 30 measures
      of social functioning are reviewed and analyzed as potential substitutes for the
      Global Assessment of Functioning Scale. The analysis focuses on the strengths and
      weaknesses of each measure for assessing functioning on axis V. RESULTS: Axis V
      measures are modestly reliable and valid but not widely used. The authors
      identify and discuss two particular limitations of the Global Assessment of
      Functioning Scale: 1) the combination of measures of symptoms and measures of
      social functioning on a single axis and 2) the exclusion of physical impairments
      from the rating of functioning. CONCLUSIONS: None of the measures of social
      functioning reviewed is clearly superior to the Global Assessment of Functioning
      Scale for use on axis V. A modified version of the Global Assessment of
      Functioning Scale, separating the measures of social and occupational functioning
      from the measures of symptoms and psychological functioning, is proposed for
      field testing, along with a new set of instructions permitting the rating of
      limitations due to both physical and mental impairments.

PMID- 1386966
TI  - New macrolide antibiotics.

PMID- 1386965
TI  - [Evaluation of preoperative risk factors].

PMID- 1386967
TI  - The effect of mutation on linkage disequilibrium.
AB  - The standard formula for the approach to linkage equilibrium between two
      diallelic loci, initially at disequilibrium, is expressed in terms of their
      probability of recombination (Li, 1955). By a simple extension, we show how to
      incorporate the effects of mutation at one or both loci. It can thereby be
      inferred that in general these effects are unlikely to be of major importance,
      contrary to some recent suggestions.

PMID- 1386968
TI  - Disulfide-linked and non-disulfide-linked gamma/delta T-cell antigen receptors:
      differential expression on T-cell lines and clones derived from normal donors and
      patients with primary immunodeficiency disorders.
AB  - We studied the expression of gamma delta T cell receptors (TCR) on T-cell lines
      and clones derived from peripheral blood lymphocytes (PBL) from certain patients
      with primary immunodeficiency disorders and normal donors. Immunoprecipitation
      with the anti-Leu 4, anti-gamma-chain and/or anti-delta-chain monoclonal
      antibodies followed by SDS-PAGE analysis revealed that 7 of 13 (54%) T-cell lines
      and clones developed from PBL of patients with primary immunodeficiency disorders
      expressed non-disulfide-linked gamma delta TCR, utilizing either the C gamma 2abc
      or the C gamma 2bc gamma-chain constant region gene segment. 5 of 13 (38%) T-cell
      lines/clones expressed disulfide-linked gamma delta TCR, whereas an additional T
      cell line was comprised of T cells expressing either disulfide-linked (C gamma 1)
      or non-disulfide-linked (C gamma 2bc) gamma delta TCR. T-cell lines and clones
      developed from four of light patients with primary immunodeficiency disorders
      exhibited exclusively non-disulfide-linked gamma delta TCR utilizing either the C
      gamma 2abc or the C gamma 2bc gamma-chain segment. T-cell lines derived from a
      fifth patient exhibited primarily non-disulfide-linked gamma delta TCR, bringing
      to five of eight the numbers of patients that expressed exclusively or primarily
      non-disulfide-linked gamma delta TCR. T-cell lines/clones derived from the
      remaining three patients exhibited exclusively disulfide-linked gamma delta TCR.
      The age of these patients varied over a wide range and there was not an
      association between their age and the type of gamma delta TCR expressed on T-cell
      lines derived from their PBL. In contrast, to these findings 14 of 16 (87.5%) T
      cell clones derived from PBL of normal donors expressed disulfide-linked gamma
      delta TCR, whereas only 2 of 16 (12.5% expressed non-disulfide linked gamma delta
      TCR. Among the T-cell clones from normal donors which express disulfide-linked
      gamma delta TCR two different types were identified. Those exhibiting under
      reducing conditions on SDS-PAGE two completely resolved polypeptide chains in the
      range of 37 kD to 44 kD, and those exhibiting under the same conditions
      indistinguishable overlapping gamma- and delta- chains in the range of 40-42 kD.
      Several T-cell lines and clones from normal donors or patients with primary
      immunodeficiency that expressed either disulfide- or non-disulfide-linked gamma
      delta TCR were delta TCS1+, demonstrating that the delta TCS1 determinant is
      expressed on both types of gamma delta TCR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1386969
TI  - Antitumor activity of 5'-deoxy-5-fluorouridine in human digestive organ cancer
      xenografts and pyrimidine nucleoside phosphorylase activity in normal and
      neoplastic tissues from human digestive organs.
AB  - 5'-Deoxy-5-fluorouridine (5'-DFUR) is believed to be metabolized to 5
      fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase). PyNPase
      activity is reported to be higher in neoplastic tissues than in normal tissues,
      and this has been proposed as an explanation for the selective cytotoxicity of 5'
      DFUR against tumors. In the present study, PyNPase activity was measured in 95
      neoplastic and normal specimens from human digestive organ tissues. In specimens
      from the esophagus, stomach, intestine and pancreas, PyNPase activity was higher
      in neoplastic tissues than in normal tissues. However, PyNPase activity in non
      malignant liver tissues, especially cirrhotic liver tissues, was much higher than
      in the normal tissues of the other digestive organs. PyNPase activity in non
      malignant liver tissues was a high as in primary liver tumors, and PyNPase
      activity in metastatic liver tumors was lower than in primary tumors and non
      malignant cirrhotic tissues. The in vivo antitumor activities of oral 5'-DFUR and
      intravenous 5-FU were also assessed in 6 human digestive organ cancer xenograft
      lines transplanted subcutaneously in nude mice, and the relationship between the
      in vivo antitumor effects of 5'-DFUR and PyNPase activity in the tumors was
      assessed. However, there was no statistically significant correlation between
      them. Although the in vivo antitumor effect of intravenous 5-FU correlated
      significantly with the in vitro sensitivity of the tumors to 5-FU (assessed by
      DNA synthesis inhibition assay), the in vivo effects of 5'-DFUR did not correlate
      with the in vitro sensitivity to 5-FU. It is suggested that: (a) the liver may be
      the major site for metabolizing 5'-DFUR to 5-FU, and (b) measuring PyNPase
      activity in the tumor may not be a useful indicator for chemotherapy with 5'
      DFUR.

PMID- 1386970
TI  - Chemoprevention of MNU-induced mammary tumors in the mature rat by 4-HPR and
      tamoxifen.
AB  - The chemopreventive efficacies of the retinoid all-trans-N-(4-hydroxyphenyl)
      retinamide (4-HPR) and the anti-estrogen tamoxifen citrate were evaluated against
      N-methyl-N'-nitrosourea (MNU) induced mammary cancer in 120-day old female
      Sprague-Dawley rats. The agents were tested alone and in combination. They were
      administered in a modified AIN-76A diet, beginning 60 days prior to a single i.v.
      dose of 50 mg MNU/kg-bw and continuing until the end of the study, 180 days post
      carcinogen treatment. At 782 mg/kg diet, 4-HPR alone significantly inhibited the
      induction of mammary adenocarcinomas compared with carcinogen controls. At 0.250
      mg/kg diet, tamoxifen alone reduced tumor incidence compared with carcinogen
      controls. At 0.125 mg/kg diet, tamoxifen was ineffective. Combinations of 782 mg
      4-HPR/kg diet with either 0.250 or 0.125 mg tamoxifen/kg diet were effective in
      inhibiting MNU-induced adenocarcinomas. The reductions in tumor incidence were
      greater for these combinations than for either agent alone. 4-HPR and 0.250 mg
      tamoxifen/kg diet decreased tumor incidence 81% (p less than 0.005), whereas 4
      HPR and 0.125 mg tamoxifen/kg diet decreased tumor incidence 72% (p less than
      0.005) compared with carcinogen controls. The combination of 391 mg 4-HPR/kg diet
      and 0.500 mg tamoxifen/kg diet was also tested and was effective in reducing
      tumor incidence.

PMID- 1386971
TI  - Suppressive effect of sesamin against 7,12-dimethylbenz[a]-anthracene induced rat
      mammary carcinogenesis.
AB  - The effects of dietary supplementation of sesamin on 7,12
      dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague
      Dawley rats were studied. Experimental diets containing 0.2% sesamin (an
      equiweight mixture of sesamin and episesamin) or 0.2% alpha-tocopheryl acetate
      were given to rats starting 1 week before intragastric administration of DMBA (10
      mg/rat). Sesamin significantly (p less than 0.05) reduced the cumulative number
      of palpable mammary cancers by 36% at 12 weeks post-DMBA administration compared
      with animals on a control diet. Alpha-tocopheryl acetate inhibited both the
      incidence and the cumulative number of mammary tumors by 20% and 45%,
      respectively. Concentrations of lipid peroxides in plasma, liver and tumors were
      all decreased in both sesamin and alpha-tocopheryl acetate groups. The activity
      of peripheral blood mononuclear cells (PBMC) increased in rats fed sesamin (140
      to 150% of the control and alpha-tocopheryl acetate groups). Fatty acid
      compositions of plasma, liver and tumor phosphatidylcholine showed a decreased
      tendency of the metabolism of linoleic acid to arachidonic acid and hence of the
      plasma concentration of prostaglandin E2 in the sesamin group. The inhibitory
      effect of sesamin on DMBA-induced mammary carcinogenesis may be ascribed, at
      least in part, to immunopotentiation and increased antioxidative activity.

PMID- 1386972
TI  - 4-week treatment of streptococcal native valve endocarditis with high-dose
      teicoplanin.
AB  - The efficacy and safety of a 4-week course of intravenous teicoplanin (500 mg
      every 12 h for the first 2 days and 10 mg/kg of body weight every 24 h
      thereafter) in the treatment of streptococcal native valve endocarditis in 20
      patients were evaluated. All blood isolates were inhibited by a concentration of
      0.12 micrograms of teicoplanin per ml. Serum bactericidal activity levels were
      measured 1/2 and 24 h after antibiotic infusion on days 5 to 7 of therapy in 19
      patients, and titers of greater than or equal to 1:32 and greater than or equal
      to 1:8, respectively, were obtained with 17 patients (89%). On the other hand,
      for two patients who were infected with teicoplanin-tolerant Streptococcus bovis,
      serum bactericidal activity levels of less than 1:2 were found. Of 20 patients, 4
      were excluded from further analysis because of protocol violation or prosthetic
      valve infection. Of the remaining 16 patients, 6 did not complete teicoplanin
      therapy because of early death (1 patient) or drug fever (5 patients). Among
      patients who developed drug fever, three who discontinued teicoplanin by day 15
      were switched to penicillin therapy, whereas the remaining two, who discontinued
      teicoplanin on day 22 and 25, respectively, did not receive any further therapy
      and have shown no relapse during the follow-up. Of 10 patients who completed
      trial therapy, 9 were cured and 1 relapsed. It is concluded that a 4-week course
      of high-dose teicoplanin may be a useful regimen for home treatment of selected
      cases of streptococcal native valve endocarditis. However, drug fever and
      infection with teicoplanin-tolerant S. bovis may be factors of concern with this
      therapeutic approach.

PMID- 1386974
TI  - [Combination therapy of doxifluridine (5'-DFUR) + cyclophosphamide (CPA) +
      tamoxifen (TAM) for advanced or recurrent breast cancer. Joint Research Group in
      the Osaka Area for Combination Therapy of 5'-DFUR with Other Drugs].
AB  - Outpatients with advanced and recurrent breast cancer were treated by a
      combination therapy of the following drugs: doxifluridine (5'-DFUR) orally
      administered at a dose of 1200 mg/day; cyclophosphamide (CPA) orally given at
      dose of 100 mg/day; and tamoxifen (TAM) orally given at dose of 20 mg daily. 5'
      DFUR and CPA were administered on consecutive days 1-14, then discontinued for 14
      days. The response rate was 44.8% including five CR and eight PR out of 29
      complete cases. As for response cases in terms of the subject lesions,
      corresponding cases were chiefly found in soft tissue and the lung. As for the
      response rate with or without pretreatment, cases previously treated showed a
      higher response rate such as 42.9% indicating that the present therapy was
      effective in pretreatment cases. The main side effect was leukopenia, but not so
      severe. Few cases with diarrhea were found. Based on the above findings, the
      present treatment is conceivably a highly useful therapy, on an outpatient basis,
      for advanced and recurrent breast cancer, especially metastatic lesions of soft
      tissue and the lung.

PMID- 1386973
TI  - In vitro activity of decaplanin (M86-1410), a new glycopeptide antibiotic.
AB  - The in vitro activity of decaplanin (formerly M86-1410), a novel glycopeptide
      antimicrobial agent, was tested against 169 gram-positive bloodstream isolates
      from patients at the University of Iowa Hospitals and Clinics and 12 selected
      vancomycin-resistant strains. Enterococcus faecalis, E. faecium, Staphylococcus
      aureus, streptococci, bacilli, corynebacteria, and listeria were inhibited by
      decaplanin (MICs for 90% of the strains tested [MIC90s], 0.12 to 4
      micrograms/ml). However, some rarely isolated and selected Enterococcus sp.
      populations had a MIC90 of 16 micrograms/ml, and S. haemolyticus strains had a
      MIC90 of 8 micrograms/ml. These in vitro results suggest that decaplanin may be
      useful against most gram-positive strains, even though some Enterococcus species
      and coagulase-negative staphylococci were potentially resistant (MICs, greater
      than or equal to 8 micrograms/ml).

PMID- 1386975
TI  - [Clinical evaluation of ondansetron (injection of a single intravenous dose)
      against nausea and emesis associated with anti-cancer drugs--dose-finding study
      in patients receiving cisplatin].
AB  - We examined anti-emetic effects, safety and the optimal dose of Ondansetron
      Injection given in a single intravenous dose in patients receiving a single high
      dose of cisplatin in randomized controlled comparative study using telephone
      registration. Ondansetron was injected intravenously in a single dose of 4 mg, 8
      mg or 12 mg, at 15 minutes before administration of cisplatin. Nausea and emesis
      were observed for 24 hours after administration of cisplatin. Efficacy rate of
      inhibitory effects on nausea and emesis were 76% (19/25 cases) in the 4 mg dose
      group, 57% (12/21 cases) in the 8 mg dose group and 83% (20/24 cases) in the 12
      mg dose group, without a statistically significant difference among 3 dose
      groups. Hence, it was estimated that the low dose of 4 mg was adequate to exert
      satisfactory anti-emetic effects. No clear relationship between onset time of the
      initial emetic episode and plasma concentrations of Ondansetron was found in 16
      cases of the 4 mg dose group, 11 cases in the 8 mg dose group and 15 cases in the
      12 mg dose group. Side effects observed during this study period were headache
      and diarrhea in 1 case in the 12 mg dose group. Both symptoms were mild and
      resolved without treatment. No abnormal findings attributable to Ondansetron were
      observed in clinical laboratory test. From the above, it was considered that
      Ondansetron given by a single intravenous injection was highly effective to
      inhibit nausea and emesis induced by cisplatin, and was highly safe. As to the
      dose, 4 mg once daily was considered to be adequate for prophylaxis of cisplatin
      induced nausea and emesis.

PMID- 1386976
TI  - [Examination of anti-emetic effect, safety and usefulness of single oral dose of
      ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose
      finding study of ondansetron tablet in patients receiving non-platinum anti
      cancer drugs].
AB  - Inhibitory effects on acute nausea and emesis, safety and usefulness of a single
      oral dose of Ondansetron tablet were evaluated in 3 different dose levels for
      comparison by telephone registration system, in patients receiving non-platinum
      anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given
      orally at 2 hrs before the initial administration of anti-cancer drugs. The
      patients were observed for 24 hours after administration of anti-cancer drugs,
      for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on
      nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14
      cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without
      statistically significant difference. Side effects were observed in 3 cases
      (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group,
      but these symptoms were not severe and disappeared after several hours or several
      days. No abnormality in clinical laboratory findings attributable to Ondansetron
      was observed. From the above, it was considered that Ondansetron was a clinically
      useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer
      drugs and that 4 mg once daily was the optimal dose.

PMID- 1386977
TI  - [Anti-emetic effect and safety of consecutive use of ondansetron injection in
      cisplatin-induced nausea and emesis].
AB  - Anti-emetic effect, safety and clinical usefulness of Ondansetron injection given
      in the dose of 4 mg once daily by intravenous administration for 3-5 consecutive
      days were examined in patients receiving a high single dose (not less than 50
      mg/m2 or over 75 mg/body) and lower multiple doses (over 15-20 mg/m2 once daily,
      for 3-5 consecutive days) of cisplatin. Efficacy rates of inhibitory effects on
      nausea and emesis in patients receiving the high single dose of cisplatin were
      76% on the 1st day, 67% on the 2nd day and 78% on the 3rd day, the average being
      71% (86/121 cases) for the 3 days. Those in patients receiving lower multiple
      doses of cisplatin were 83% on the 1st day, 78% on the 2nd day, 61% on the 3rd
      day, 65% on the 4th day and 57% on the 5th day, the average being 72% (13/18
      cases) for the 3-5 days. Side effects were observed in 15 cases out of 207 (1st
      course, 182 cases; 2nd course, 21 cases; 3rd course, 4 cases), and major symptoms
      were headache and fever. Also, abnormalities in clinical laboratory findings
      attributable to Ondansetron were observed in 13 cases, mainly consisting of
      elevation of the hepatic function values. From the above, Ondansetron injection
      which showed sufficient anti-emetic effects on acute emesis and delayed emesis
      induced by a high single dose or lower multiple doses of cisplatin with its once
      daily intravenous dose given for 3-5 consecutive days, were considered a safe and
      clinically useful anti-emetic.

PMID- 1386978
TI  - [Examination of anti-emetic effect and safety of multiple intravenous doses of
      ondansetron in patients receiving nonplatinum anti-cancer drugs].
AB  - Anti-emetic effects, safety and usefulness of Ondansetron given intravenously at
      4 mg once daily for consecutive 3-5 days were investigated against nausea and
      emesis induced by non-platinum anticancer drugs. Efficacy rates in control of
      nausea and emesis were 59% (20/34 cases) and 68% (23/34 cases), respectively. The
      efficacy rate for inhibition of nausea and emesis, calculated based on the
      control of nausea and emesis, was 68% (23/34 cases). Adverse events (headache and
      constipation) were observed in 1 case and abnormal change in clinical laboratory
      findings (increase in eosinophil count) in another case. Out of 42 cases in which
      safety was evaluated, 41 (98%) cases were assessed as "no problem in safety."
      However, one case with side effect was assessed as a "Minor problem in safety."
      From the above, it was confirmed that Ondansetron injection exerted excellent
      inhibitory effects against nausea and emesis induced by non-platinum anti-cancer
      drugs, and this drug was a highly safe and useful anti-emetic.

PMID- 1386979
TI  - [A case of gastric cancer with recurrent bone metastases successfully treated
      with induced hypertension chemotherapy using cisplatin].
AB  - A sixty-eight-year-old female with bone metastases from gastric cancer
      successfully treated with induced hypertension chemotherapy using cisplatin is
      reported. She had undergone R2 curative subtotal gastrectomy in June 1985, and
      had orally taken tegafur 600 mg/day and then changed to doxifluridine 800 mg/day
      as postoperative adjuvant chemotherapy. Five months after the operation she had
      back pains and both 99mTc-MDP and 67Ga-citrate scintigram showed L1 vertebra and
      rib bone metastasis. Induced hypertension chemotherapy using cisplatin was then
      intermittently performed from January 1986 to September 1990, a single course of
      which was 25 mg/body div x 2/week for serial 4 weeks; a total of seven courses
      were carried out and consequently the total volume of the administered cisplatin
      reached 1,100 mg. Neither medullar nor renal toxicities were observed, but mild
      gastrointestinal symptoms were noted. The patient no longer has back pains, and
      no signs of bone metastases were seen on both scintigrams for two years and eight
      months from December 1988 to August 1991. This case is very rare because her bone
      metastases were successfully treated with induced hypertension chemotherapy using
      cisplatin. However, metastatic bone tumors from gastric cancer usually resist any
      treatments. It is expected that the successfully treated patients even with bone
      metastasis will be increasingly reported from now as various new approaches
      including induced hypertension chemotherapy are introduced.

PMID- 1386980
TI  - Sensitivity of hysterosalpingography after tubal surgery.
AB  - Hysterosalpingography (HSG) to assess tubal patency in the postoperative
      evaluation of the infertile patient has been well described. However, the
      sensitivity and specificity of HSG after tubal surgery has not been reported. We
      correlated HSG and laparoscopic findings in 25 patients who had tubal surgery
      (microsurgical tubal reanastomoses [11] and distal salpingostomies [14]). HSG
      provided a more reliable means of assessing tubal patency (sensitivity and
      specificity of 96% and 61% respectively) than in detecting pelvic adhesive
      disease (PAD) (sensitivity and specificity of 12% and 75% respectively)
      regardless of tubal surgical procedure. HSG was associated with a high false
      negative rate (60%) due primarily to the inability to detect PAD. Complete
      agreement between HSG and laparoscopy was noted in only 15% of cases. These data
      suggest that HSG is a sensitive means to determine tubal patency, but was not
      sufficiently sensitive or specific to detect PAD after tubal surgery. These
      limitations should be noted in the interpretation of HSG in any infertile patient
      with a history of tubal surgery, and severely limits the application of HSG to
      the management of the post-operative infertile patient.

PMID- 1386981
TI  - Laparoscopic cholecystectomy in the obese patient.
AB  - The authors' experience with laparoscopic cholecystectomy (LC) in obese (O, n =
      96) and morbidly obese (MO, n = 27) patient groups was compared with that in the
      normal weight (NW, n = 174) group of patients as well as the whole group (WG).
      There were no operative deaths. There were no significant differences between
      groups for any of the following: successful intraoperative cholangiography (WG,
      52.2%; NW, 52.9%; O, 51.1%; MO, 55.6%), conversion to open cholecystectomy (WG,
      9.6%; NW, 9.2%; O, 10.4%; MO, 11.1%), incidence of major complications (WG, 4.1%;
      NW, 3.4%, O, 5.2%; MO, 0%), incidence of minor complications (WG, 7.4%, NW, 7.5%;
      O, 6.3%; MO, 3.7%), and length of hospitalization after successful LC (WG, 1.25
      days; NW, 1.31 days; O, 1.16 days; MO, 1.13 days). Duration of operation did not
      differ except LC in the MO group (136.4 +/- 6.9 minutes) was longer when compared
      with NW patients (123.0 +/- 2.9 minutes, p less than 0.05). The authors conclude
      LC is a safe and effective treatment for obese patients with symptomatic
      cholelithiasis.

PMID- 1386983
TI  - The use of drugs in emergency airway management in pediatric trauma.
AB  - Most patients who require emergency airway control receive drugs to induce
      rapidly sufficient anesthesia for direct laryngoscopy and endotracheal
      intubation, but there are no protocols that outline the use of specific drugs in
      general use. Drugs should safely and rapidly produce (1) unconsciousness; (2)
      paralysis; and (3) blunt intracranial pressure (ICP) responses to airway
      procedures. Consequences to be considered include increased ICP, hemorrhagic
      shock, and a full stomach. To refine the use of drugs used for airway procedures
      in pediatric trauma patients, the authors reviewed all cases of emergency
      endotracheal intubation over a recent 12-month period (1) to see whether
      medications used met the goals of producing unconsciousness and paralysis and
      blunting ICP responses were met safely; and (2) to identify potential drug
      related complications. From July 1, 1990, to June 30, 1991, 60 of 791 children
      (7.6%) required endotracheal intubation at the scene of injury, at the referring
      hospital, or in our emergency department (15; 25%). Ten patients died (16.7%).
      Three fourths were younger than 9 years of age. All except one suffered blunt
      injuries. Nearly all (95%) suffered head injuries, isolated in 39 of 57 (68.4%)
      and combined with injuries in other regions in 18 (31.6%). Fifteen patients were
      in apnea (25%); seven were both apneic and pulseless. Three fourths (45 of 60)
      had diminished levels of consciousness; one fourth (15 of 60) were awake.
      Immediate endotracheal intubation proceeded appropriately without drugs in all
      seven patients in cardiopulmonary arrest. Only eight of the remaining 53 patients
      (15.1%) received an optimal medication regimen. Many patients with head injury
      were inadequately protected against increases in ICP. Thiopental, an effective
      anesthetic agent that effectively lowers intracranial pressure, was not used in
      25 of 35 stable patients with isolated head injury (71.4%). Intravenous lidocaine
      was not used in 38 of 50 head-injured patients in whom it would have been an
      appropriate adjunct to control increases in ICP (76%). Eight patients received
      paralyzing agents alone, without sedatives or narcotics. Medications were thought
      inadequate to relieve the pain and discomfort of laryngoscopy and endotracheal
      intubation in 32 of the 53 patients who should have received them (60.4%). No
      paralyzing agents were used in 36 of the 53 instances where it would have been
      appropriate (67.9%). In two of 11 instances (18.3%) where succinylcholine was
      administered, no prior nondepolarizing agent was used. Complications of a full
      stomach at the time of emergency endotracheal intubation became evident in 10
      patients (16.7%) who vomited during procedures to control the airway. Two
      patients (3.3%) aspirated.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1386984
TI  - Ganglioside GM2 levels in human melanoma cells: inverse correlation with
      lysosomal beta-hexosaminidase A activity.
AB  - GM2 is usually significantly elevated in human melanoma cells. The lysosomal
      hydrolase beta-hexosaminidase A (Hex A), is an isoenzyme required for terminal
      GalNAc hydrolysis from intact GM2 to GM3. The objective of the present studies is
      to determine if the elevated levels of gangliosides, particularly GM2, correlate
      with the activity of Hex A in cultured melanoma cells. The Hex A activity in 13
      melanoma cell lines ranged from 26%-88.3% There was a inverse correlation between
      GM2 nmole/g and Hex A activity (r = -0.48; p less than 0.003). An inverse
      correlation (p less than 0.03) occurred between GD2 nmole/g and Hex A activity.
      There was an inverse correlation (r = -0.53; p less than 0.05 and r = -0.51; p
      less than 0.05, respectively) between the ratio of substrate/product (GM2/GM3)
      and (GD2/GD3) and Hex A activity. These results indicate that the level of GM2 in
      melanoma is inversely correlated with the level of activity of Hex A.

PMID- 1386982
TI  - Early enteral feeding, compared with parenteral, reduces postoperative septic
      complications. The results of a meta-analysis.
AB  - This two-part meta-analysis combined data from eight prospective randomized
      trials designed to compare the nutritional efficacy of early enteral (TEN) and
      parenteral (TPN) nutrition in high-risk surgical patients. The combined data gave
      sufficient patient numbers (TEN, n = 118; TPN, n = 112) to adequately address
      whether route of substrate delivery affected septic complication incidence. Phase
      I (dropouts excluded) meta-analysis confirmed data homogeneity across study
      sites, that TEN and TPN groups were comparable, and that significantly fewer TEN
      patients experienced septic complications (TEN, 18%; TPN, 35%; p = 0.01). Phase
      II meta-analysis, an intent-to-treat analysis (dropouts included), confirmed that
      fewer TEN patients developed septic complications. Further breakdown by patient
      type showed that all trauma and blunt trauma subgroups had the most significant
      reduction in septic complications when fed enterally. In conclusion, this meta
      analysis attests to the feasibility of early postoperative TEN in high-risk
      surgical patients and that these patients have reduced septic morbidity rates
      compared with those administered TPN.

PMID- 1386985
TI  - Fetal gastro-intestinal and abdominal wall defects: associated malformations and
      chromosomal abnormalities.
AB  - During an 8-year period (1983-1991), blood karyotyping was performed in 235
      fetuses with abdominal wall or gastro-intestinal tract defects. The overall
      incidence of chromosomal abnormalities was 29% (trisomy 21, n = 12; trisomy 18, n
      = 44; trisomy 13, n = 7; deletion of the short arm of chromosome 5, n = 1;
      unbalanced translocation involving chromosomes 4 and 15, n = 1; triploidy, n = 1;
      Klinefelter's syndrome, n = 1; and Beckwith-Wiedemann syndrome with mosaic
      duplication 11p15, n = 1). The karyotype was abnormal in 42 (36%) of the 116
      fetuses with exomphalos, in none of the 26 with gastroschisis, in 10 (43%) of the
      23 with duodenal atresia, in 18 (75%) of the 24 with lack of visible stomach, in
      1 (4%) of the 24 with dilated bowel and in 2 (7%) of the 27 with echogenic
      hepatic nodules or abdominal cysts. Abnormal karyotypes were more commonly
      encountered when there was ultrasonographic evidence of multiple malformations
      (43%) compared to isolated defects (2%). Survival in fetuses with exomphalos
      (33%), absent stomach (4%), and large bowel obstruction (13%) was poor, whereas
      in those with gastroschisis (73%) or abdominal cysts (88%) survival was high; in
      small bowel obstruction and in duodenal atresia, survival was 65 and 57%,
      respectively.

PMID- 1386986
TI  - Fetal T-lymphocyte subpopulations in normal pregnancies.
AB  - Peripheral blood T lymphocyte subpopulations were measured, using a fluorescence
      activated cell sorter, in fetal blood samples obtained either by cordocentesis (n
      = 118) or at elective caesarean section (n = 14). Both the numbers and
      percentages of the total T lymphocytes (CD3+) and T-helper lymphocytes (CD4+)
      increased exponentially with gestation from respective means of 46% (1.15 x
      10(9)/l) and 29% (0.70 x 10(9)/l) at 16 weeks to a plateau of 75% (3.11 x
      10(9)/l) and 54% (2.10 x 10(9)/l) at 34 weeks. Similarly, the number of
      suppressor/cytotoxic T lymphocytes (CD8+) increased linearly with gestation from
      a mean of 22% (0.55 x 10(9)/l) at 16 weeks to 24% (0.96 x 10(9)/l) at 40 weeks;
      there were no natural cytotoxic T lymphocytes (CD3+CD56+) in any of the fetal
      blood samples. The helper-to-suppressor T lymphocyte ratio (CD4/CD8) increased
      exponentially with gestation from a mean of 1.22 at 16 weeks to 2.57 at 28 weeks.
      The alterations in T lymphocyte subpopulations were accompanied by changes in the
      expression of CD45RA, L-selectin, CD25 and HLA-DR. These alterations in T
      lymphocyte subpopulations with gestation reflect the pattern of maturation and
      development of the fetal cell-mediated immune system.

PMID- 1386987
TI  - Pathophysiology of polyhydramnios in twin transfusion syndrome.
AB  - In 3 cases of severe twin transfusion syndrome we demonstrate that the
      concentration of atrial natriuretic factor (ANF) in the cord blood of recipient
      twins is significantly elevated compared to that of donor twins. The discrepancy
      between recipient and donor concentration correlates with the volume of
      transfusion. The following pathophysiological mechanism for explaining
      polyhydramnios in recipient twins is proposed: chronic overload in recipient
      twins causes enhanced release of ANF from the fetal heart. Consequently,
      increased fetal urine production leads to polyhydramnios, which is additionally
      enhanced by inhibition of ADH release.

PMID- 1386988
TI  - N-methyl-D-aspartate receptor antagonist MK-801 and spatial memory
      representation: working memory is impaired in an unfamiliar environment but not
      in a familiar environment.
AB  - Female Sprague-Dawley rats were injected with the noncompetitive N-methyl-D
      aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in
      spatial working memory (WM) and reference memory (RM) procedures in an 8-arm
      radial maze. MK-801 impaired RM and WM acquisition but not performance when rats
      were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr
      delay between the first and last 2 correct WM choices impaired long-term WM. MK
      801 impaired WM performance in trained rats only when rats were tested in a new
      environment. Thus, 2 mechanisms may be required for relational memory: an NMDA
      dependent mechanism for acquiring long-term spatial representations and an NMDA
      insensitive mechanism for operating on these stored representations.

PMID- 1386989
TI  - MK-801 prevents brain lesions and delayed-nonmatching-to-sample deficits produced
      by pyrithiamine-induced encephalopathy in rats.
AB  - Rats were trained on a spatial delayed-nonmatching-to-sample (DNMTS) task and
      assigned by block randomization to one of four treatments: pyrithiamine-induced
      thiamine deficiency (PTD), PTD with administration of MK-801 after 12 days,
      control with MK-801 treatment, and control without MK-801. After 15 days of
      treatment followed by 21 days of recovery, the PTD rats showed significant
      deficits for DNMTS accuracy at retention intervals (RI) that ranged from 3.0 s to
      15.0 s, the RIs that produced 75% accuracy on DNMTS in staircase training, and
      the rate at which a novel radial arm maze task was learned. The PTD-treated rats
      had consistent lesions in the thalamus and the mammillary bodies. MK-801
      protected rats from both behavioral deficits and brain lesions (assessed
      quantitatively and qualitatively) that were produced by the PTD treatment.

PMID- 1386990
TI  - Oncogenes, onco-suppressors, carcinogenesis and oral cancer.
AB  - The regulation of cell growth is fundamental to the maintenance of health:
      disturbed regulation can result in neoplasia. Genes in normal cells
      (protooncogenes) code for proteins involved in the regulation of cell growth and
      differentiation; abnormalities in these genes (oncogenes) or their expression are
      often involved in the development of cancer. This paper summarises the essentials
      of the complex cell growth regulatory mechanisms, their genetic control, and
      their disturbances in neoplasia, emphasising the role of cancer-promoting
      (oncogenes) and suppressing genes (onco-suppressors or anti-oncogenes),
      especially in relation to oral carcinoma, and discusses the possible role of
      viruses as one cause of neoplasia.

PMID- 1386991
TI  - Better predictor of survival for colorectal cancer patients identified.

PMID- 1386992
TI  - Radionuclide therapy relieves pain from bone metastases.

PMID- 1386993
TI  - Spiral CT scans reduce cost.

PMID- 1386994
TI  - Women with AIDS will soon outnumber men.

PMID- 1386996
TI  - Clinical trials referral resource. Head and neck cancer.

PMID- 1386995
TI  - The role of secondary cytoreductive surgery in epithelial ovarian malignancies.
AB  - The benefit of aggressive primary cytoreductive surgery in the management of
      patients with advanced epithelial ovarian cancer has been confirmed. The value of
      secondary cytoreductive surgery, however, is less clear. This approach is being
      studied in four categories of patients: (1) those clinically free of disease
      after a planned regimen of first-line chemotherapy who are found to have
      macroscopic tumor at second-look laparotomy; (2) patients found to have bulky,
      unresectable tumor at initial surgery and who undergo interval cytoreduction as
      part of a planned chemosurgical treatment approach; (3) those with recurrent
      disease after a prolonged disease-free interval; and (4) patients who progress on
      first-line therapy. This article reviews the technical success rates,
      complications, and survival in patients undergoing these secondary cytoreductive
      procedures.

PMID- 1386997
TI  - Current status of chemoprevention of head and neck cancer.
AB  - Chemoprevention involves efforts to block or reverse carcinogenesis before the
      development of invasive cancer. Natural agents, such as retinol and beta
      carotene, as well as synthetic retinoids have been studied as potential
      chemopreventive agents. In the head and neck, chemoprevention studies have
      included efforts both to reverse premalignant lesions such as oral leukoplakia
      and to prevent the development of second primary tumors. In one recent trial,
      high-dose 13-cis-retinoic acid treatment resulted in a dramatic reduction in the
      incidence of second primary tumors. However, significant toxicities were
      associated with the high dosage. This trial, as well as previous studies of oral
      leukoplakia, have led to the development of a chemoprevention trial using a low
      dose of 13-cis-retinoic acid to prevent second primary tumors following head and
      neck cancer. The rationale and design of this study are discussed in detail.

PMID- 1386998
TI  - Stanford opens AIDS trials to residents of underserved communities.

PMID- 1386999
TI  - Leukocytes in the intestinal epithelium: an unusual immunological compartment
      revisited.
AB  - Intraepithelial lymphocytes (IEL) are characterized by significant heterogeneity
      in morphology, surface antigen expression, and function. Although IEL can express
      T cell markers including the T cell receptor (TcR), their relationship to
      peripheral T cells is not clear. The finding of IEL in athymic nude mice first
      suggested that a number of IEL may be thymic-independent. The identification of
      the gamma/delta TcR heterodimer on IEL further suggested that these cells are
      part of a distinct population of epithelial-associated lymphocytes, many of which
      express the gamma/delta TcR. We review the nature of the V gamma gene usage in
      IEL and highlight the differences between different gamma/delta T cell
      populations. The thymic independent nature of these gamma/delta cells is
      discussed and compared to that of the alpha/beta TcR expressing IEL. The finding
      that some alpha/beta IEL can develop independent of thymic processing suggests
      that IEL are characterized by a unique collection of T cells that may undergo
      differentiation within the intestinal compartment. The ability to distinguish T
      dependent from T-independent IEL raises the possibility of identifying the
      functional nature of these two IEL lineages. We propose that the ability of IEL
      to potentially undergo repertoire selection in the intestine could allow for the
      development of mucosal T cells uniquely adapted to function in this environment.

PMID- 1387000
TI  - The presence of scatter factor in patients with metastatic spread to the pleura.
AB  - Pleural effusion fluid obtained from eleven patients with metastatic spread to
      the pleura was screened for the ability to cause the dispersal--'scattering'--of
      MDCK colonies in vitro. Four of these samples proved to be positive using this
      assay. Of these two had titres high enough to warrant further purification on a
      cation exchange Mono S column. Active material from both lung samples, eluted at
      the same positions as factor from cultured human lung fibroblasts (MRC-5) and
      human placenta but in a slightly different position to murine scatter factor. In
      both cases the semi-purified active agent was identified as hepatocyte growth
      factor/scatter factor (HGF/SF) using an ELISA detection system specific for human
      HGF/SF. This is the first report identifying the presence of significant amounts
      of HGF/SF in the pleura of patients where malignant spread has occurred.

PMID- 1387002
TI  - Fundraising: targeting telethon.

PMID- 1387001
TI  - Cyclophosphamide decreases O6-alkylguanine-DNA alkyltransferase activity in
      peripheral lymphocytes of patients undergoing bone marrow transplantation.
AB  - O6-alkylguanine-DNA-alkyltransferase (ATase) levels were measured in extracts of
      peripheral blood lymphocytes taken at various times during chemotherapy from 19
      patients with various haematological malignancies. Seven patients with advanced
      Hodgkin's disease received preparative treatment consisting of cyclophosphamide
      (1.5 g m-2, daily) administered on days 1 to 4 and BCNU (600 mg m-2) on day 5
      prior to autologous bone marrow rescue (ABMR) delivered on day 7. Treatment in
      the remaining 12 patients consisted of cyclophosphamide (1.8 g m-2, daily) given
      on days 1 and 2 followed at day 4 with total body irradiation (TBI) administered
      in six fractions over the subsequent 3 days to a total dose of 1200 cGy prior to
      bone marrow transplantation. In the Hodgkin's group, significant decreases in
      ATase activity were seen during the cyclophosphamide treatment, and the median
      ATase nadir was 32% (range 0% to 57%) of pretreatment levels following 4 days of
      cyclophosphamide. In one patient, no ATase activity was detectable following the
      4th cyclophosphamide treatment. ATase activities decreased further after BCNU
      administration to a median of 19% (range 0% to 32%) of pretreatment levels.
      Extensive cyclophosphamide-induced reduction of lymphocyte ATase levels was also
      seen in the other group of 12 patients treated with cyclophosphamide/TBI:
      postcyclophosphamide median ATase nadir was 35% (range 12% to 78%) of the
      pretreatment levels. No ATase depletion was seen when cyclophosphamide (up to 10
      mM) was incubated for 2 h with pure recombinant human ATase in vitro whereas
      ATase activity was reduced by 90% on preincubation with 100 microns acrolein or
      with greater than 1 mM phosphoramide mustard. This suggests that a
      cyclophosphamide-induced decrease in ATase levels in human peripheral lymphocytes
      in vivo may be due to depletion mediated by the production of intracellular
      acrolein. Since ATase appears to be a principal mechanism in cellular resistance
      to the cytotoxic effects of BCNU and related alkylating agents, these
      observations suggest that a cyclophosphamide-induced reduction in ATase activity
      may be an additional factor in the effectiveness of the combined sequential
      therapy.

PMID- 1387003
TI  - Reconstitution of the sarcoplasmic reticulum Ca(2+)-ATPase: mechanisms of
      membrane protein insertion into liposomes during reconstitution procedures
      involving the use of detergents.
AB  - The Ca(2+)-ATPase from skeletal muscle sarcoplasmic reticulum was reconstituted
      into sealed phospholipid vesicles using the method recently developed for
      bacteriorhodopsin (Rigaud, J.L., Paternostre, M.T. and Bluzat, A. (1988)
      Biochemistry 27, 2677-2688). Liposomes prepared by reverse-phase evaporation were
      treated with various amounts of Triton X-100, octyl glucoside, sodium cholate or
      dodecyl octa(oxyethylene) glycol ether (C12E8) and protein incorporation was
      studied at each step of the liposome solubilization process by each of these
      detergents. After detergent removal by SM-2 Bio-Beads the resulting vesicles were
      analyzed with respect to protein incorporation by freeze-fracture electron
      microscopy, sucrose density gradients and Ca2+ pumping measurements. The nature
      of the detergent used for reconstitution proved to be important for determining
      the mechanism of protein insertion. With octyl glucoside, direct incorporation of
      Ca(2+)-ATPase into preformed liposomes destabilized by saturating levels of this
      detergent was observed and gave proteoliposomes homogeneous in regard to protein
      distribution. With the other detergents, optimal Ca(2+)-ATPase pumping activities
      were obtained when starting from Ca(2+)-ATPase/detergent/phospholipid micellar
      solutions. However, the homogeneity of the resulting recombinants was shown to be
      dependent upon the detergent used and in the presence of Triton X-100 or C12E8
      different populations were clearly evidenced. It was further demonstrated that
      the rate of detergent removal drastically influenced the composition of resulting
      proteoliposomes: upon slow detergent removal from samples solubilized with Triton
      X-100 or C12E8, Ca(2+)-ATPase was found seggregated and/or aggregated in very few
      liposomes while upon rapid detergent removal compositionally homogeneous
      proteoliposomes were obtained with high Ca2+ pumping activities. The
      reconstitution process was further analyzed by centrifugation experiments and the
      results demonstrated that the different mechanisms of reconstitution were driven
      predominantly by the tendency for self-aggregation of the Ca(2+)-ATPase. A model
      for Ca(2+)-ATPase reconstitution was proposed which accounted for all our
      results. In summary, the advantage of the systematic studies reported in this
      paper was to allow a rapid and easy determination of the experimental conditions
      for optimal detergent-mediated reconstitution of Ca(2+)-ATPase. Proteoliposomes
      prepared by the present simple method exhibited the highest Ca2+ pumping
      activities reported to date in Ca(2+)-ATPase reconstitution experiments performed
      in the absence of Ca2+ precipitating agents.

PMID- 1387004
TI  - A prospective evaluation of the cumulative illness rating scale.
AB  - Assessment of overall physical health is an important yet little studied problem
      in geriatric research. The Cumulative Illness Rating Scale (CIRS) was among the
      first instruments that attempted to summarize the overall severity of illness
      based on clinical information. This study evaluated the CIRS in a prospective
      longitudinal study of 181 elderly (mean age +/- SD = 79 +/- 7.4) subjects
      undergoing comprehensive geriatric assessment in an outpatient unit. The CIRS was
      found to correlate negatively with activities of daily living (r = -0.49, p =
      0.0001), instrumental activities of daily living (r = -0.34, p = 0.0001), patient
      morale (r = -0.30, p = 0.0001), and positively with days in hospital (r = 0.21, p
      = 0.0075) and number of medications (r = 0.31, p = 0.0001). Mean CIRS scores for
      subjects who died during follow-up were significantly higher than the scores for
      survivors (p less than 0.01). In logistic regression, CIRS was a significant
      predictor of death, yet it did not improve that prediction over information
      contained in measures of activities of daily living. In separate logistic
      analyses, CIRS and age predicted acute care hospital days during follow-up, while
      ADL or IADL predicted the use of nursing home services. Although the CIRS appears
      to be a reliable method of summarizing medical information and to have some
      external validity, in its present form it does not provide additional prognostic
      information.

PMID- 1387005
TI  - Modulation of neutrophil functions by gamma-interferon.

PMID- 1387006
TI  - Biochemical effects of human granulocyte-macrophage colony-stimulating factor (GM
      CSF) on the human neutrophil.
AB  - Through studies of the stimulus-response coupling of GM-CSF in the neutrophils,
      important clues to the nature of the signal transduction of GM-CSF receptors are
      starting to emerge. GM-CSF receptors which have to date been identified and
      characterized biochemically appear to be too small to contain internal tyrosine
      kinase domains. Nonetheless, tyrosine phosphorylation of five separate proteins
      results when neutrophils are incubated with GM-CSF (73). The most appealing
      explanation for this interesting observation is that one or more tyrosine kinases
      lie distal to GM-CSF receptors in their signal transduction pathway. While less
      likely, the possibility exists that another class of GM-CSF receptors which
      exhibit intrinsic tyrosine kinase activity remains to be identified.
      Characterization of the specific proteins which are phosphorylated on tyrosine
      residues ought to provide important insights into the signal transduction of this
      cytokine. On the other hand, direct activation of protein kinases C has not been
      observed following exposure of neutrophils to GM-CSF (19,22,80). GM-CSF induces
      the release of small quantities of arachidonic acid from the plasma membrane of
      the neutrophil (22). Arachidonic acid is primarily released directly through the
      effects of phospholipases A2 on membrane phospholipids or indirectly through
      activation of phospholipases C or D, which release compounds that can serve as a
      source of arachidonic acid when hydrolyzed by specific enzymes. Direct activation
      of phospholipases C in the neutrophil by GM-CSF appears most unlikely, since GM
      CSF does not elevate [Ca2+]i or induce the release of detectable quantities of
      inositol trisphosphates or diacylglycerols in these cells. Therefore, the
      possibility that GM-CSF may directly activate phospholipases A2 is quite
      plausible. GM-CSF directly activates Na+/H+ antiporters in the plasma membrane of
      the neutrophil, resulting in alkalinization of the cytoplasm of approximately 0.1
      0.25 pH unit (73). The function of cytoplasmic alkalinization in the priming of
      mature neutrophils is unclear. However, evidence exists in other cell systems
      that cytoplasmic alkalinization may be important in inducing cell proliferation,
      since the pH optima of several enzymes necessary for DNA synthesis are slightly
      more alkaline than the resting pH of the cytosol. Many types of growth factors
      which initiate cell division through occupancy of surface receptors give rise to
      cytoplasmic alkalinization through just such a mechanism (52). Therefore, it
      seems likely that GM-cSF may activate Na+/H+ antiporters in the plasma membranes
      of hemic progenitor cells which bear GM-CSF receptors and which proliferate in
      response to this cytokine.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1387007
TI  - [Hemostatic disorders following polytrauma--the role of physiologic coagulation
      inhibitors during the preclinical phase].
AB  - Coagulation changes due to polytrauma are considered to be an important
      determinant for the outcome. In this context, physiological inhibitors of
      activated coagulation are highlighted with special reference to antithrombin-III
      (AT-III). Blood samples of 20 randomly selected adults with polytrauma (Injury
      Severity Score mean = 36.7 +/- 8.6) were investigated. To investigate the very
      early onset of coagulation changes, samples were taken as early as possible at
      the site of emergency (mean = 18.3 +/- 5.5 min. after trauma) as well as at
      hospital admission (mean = 78.0 +/- 10.4 min.). By means of a specially designed
      "mini-lab", basic processing of the samples harvested (centrifugation, pipetting,
      freezing) was done on the spot to obtain haemostaseological results that agree as
      closely as possible with the subsequent analyses. Due to the activation of
      intravascular coagulation as well as the consumption of physiological inhibitors,
      comprehensive coagulation disturbances become obvious at the time of hospital
      admission. These are intensified by haemodilution as a consequence of high-dose
      fluid replacement. However, significantly elevated levels of specific coagulation
      reaction products (thrombin-antithrombin-III-complex) give evidence of the
      consumption of inhibitory potential exceeding haemodilution.

PMID- 1387010
TI  - Bioelectrorheological model of the cell. 3. Viscoelastic shear deformation of the
      membrane.
AB  - An analytical electromechanical model of a spherical cell exposed to an
      alternating electric field was used to calculate shear stress generated in the
      cellular membrane. Shape deformation of Neurospora crassa (slime) spheroplasts
      was measured. Statistical analysis permitted empirical evaluation of creep of the
      cellular membrane within the range of infinitesimal stress. Final results were
      discussed in terms of various rheological models.

PMID- 1387008
TI  - Angiotensin II receptor antagonist losartan has persistent effects on blood
      pressure in the young spontaneously hypertensive rat: lack of relation to
      vascular structure.
AB  - The persistent effects on blood pressure of the angiotensin II receptor
      antagonist losartan and the converting enzyme inhibitor captopril were compared
      in the young spontaneously hypertensive rat (SHR). Losartan (DuP753/MK954, 15
      mg/kg/day) and captopril (100 mg/kg/day) were given in the drinking water of 3
      week-old SHRs for 4- and 10-week durations. Blood pressure was measured during
      treatment and after treatment was stopped until the age of 30 weeks. Both
      losartan and captopril given for 4 and 10 weeks prevented the development of
      hypertension during treatment and redevelopment of hypertension after treatment
      was stopped. Treatment for 10 weeks was more effective than for 4 weeks in
      lowering long-term pressure. Four weeks of treatment did not affect the
      mesenteric resistance artery media/lumen (m1/l1) ratio. In contrast, both
      losartan and captopril given for 10 weeks resulted in large and significant
      reductions in m1/l1 [5.3 +/- 0.8 and 5.63 +/- 0.8 vs 7.7 +/- 0.8 x 10(-2) (SD), p
      less than 0.001]. In losartan-treated rats, plasma renin and angiotensin II
      concentration were increased between 4- and 7-fold at the end of both treatment
      periods. These findings show losartan to be an effective antihypertensive agent
      and support data implicating angiotensin II in the early events leading to
      hypertension in this model. The abilities of losartan and captopril to affect
      blood pressure without affecting vascular structure suggest that the latter is a
      poor predictor of long-term hypertensive levels in the SHR.

PMID- 1387009
TI  - Eicosanoid-dependent and endothelium-independent oscillations of rat aorta.
AB  - We studied the role of endothelium and eicosanoids in rhythmic contractions of
      rat thoracic aorta. Spontaneous oscillations were observed in 35% of 385
      endothelium-intact and in 46% of 22 endothelium-denuded aortic strips from
      normotensive Sprague-Dawley male rats. Vasoactive agents (norepinephrine,
      epinephrine, phenylephrine, isoproterenol, arachidonic acid, PGF2 alpha,
      serotonin, potassium, endothelin, atrial natriuretic factor and angiotensin II)
      induced rhythmic contractions in the majority of tissues. Rhythmic activity was
      also observed in aortic strips from adult female, pregnant and old male rats.
      Aortic oscillations were partially inhibited by indomethacin, ibuprofen and
      nordihydroguaiaretic acid (NDGA), and completely inhibited by indomethacin plus
      NDGA, nifedipine, low external calcium (less than 1 mM) and pretreatment with
      dexamethasone. Indomethacin, NDGA and arachidonic acid did not affect
      oscillations of the portal vein. Rhythmic contractions were observed in thoracic
      aortic strips from neonatal but not from adult rabbits. However, oscillations
      could be induced in strips of the mesenteric artery and terminal abdominal aorta
      of adult rabbits. Also, adult rabbit thoracic aortic strips exhibited
      oscillations when set up in close proximity of rat aorta. It is suggested that
      rhythmic contractions are physiological characteristics of many and perhaps all
      blood vessels and may play a role in blood flow and turbulence; the likely cause
      of these oscillations is the cyclic release of one or more eicosanoids.

PMID- 1387012
TI  - Prevalence of spinal pain among the staff of a district health authority.
AB  - Being aware of the many neck and back problems which occur among staff, the
      departments of Occupational Medicine and Physiotherapy initiated a study to
      ascertain the scale of the problem among employees of the district health
      authority. A questionnaire was sent to a 10 per cent sample, stratified by
      occupation, of the 16,000 employees of a district health authority of which 84
      per cent (1363) responded. Over half of all respondents had had a significant
      degree of spinal pain in the past year, mainly located in the back. In over half
      of those with pain, their discomfort had been significant enough to interfere
      with sport, work and sleep. Over one-quarter said they had taken time off work
      for spinal pain in the past five years. Nearly half of respondents under 25 years
      of age had some degree of spinal pain. Although a very small group, ambulance
      workers appear to have the greatest problems. Staff involved in lifting equipment
      and manual work had a lower prevalence of spinal pain than nurses or ambulance
      workers, but were more likely to have severe pain for which analgesics were
      taken. Nurses had a prevalence rate of 60 per cent, but less than one third had
      frequent or severe pain. Based upon this information an application has been made
      to implement a programme to reduce both the number of injuries and the severity
      of those that occur.

PMID- 1387011
TI  - Injectable and implantable contraceptives.
AB  - In December 1990, the Food and Drug Administration approved Norplant (Wyeth
      Ayerst, Radnor, PA) for general US use. This approval comes during a time period
      when the number of contraceptors relying on sterilization has risen, echoing
      known dissatisfaction with other reversible methods. During the past year, data
      have been presented that refute concern that Norplant may be an abortifacient.
      Continued estradiol production with development of follicles and ovulation in
      regularly menstruating women was documented. Ovulatory dysfunction among Norplant
      users, despite follicular development, was also detailed. Changes in carbohydrate
      metabolism were confirmed to be clinically insignificant. International
      development of biodegradable and non-biodegradable implants and 1, 3, or 6 months
      injectables continues. These injectable and implantable contraceptives promise
      diversity in contraceptive options to match diversity in contraceptive need and
      life style.

PMID- 1387013
TI  - Cardiovascular and sympathetic nervous response to dynamic exercise in patients
      with essential hypertension.
AB  - To investigate the relationship among systolic blood pressure (SBP) during
      exercise (EX), left ventricular hypertrophy (LVH) and plasma norepinephrine
      concentration (NE) in patients with essential hypertension (HT), 20 patients with
      HT and 20 age- and sex-matched normal subjects were studied using treadmill
      testing. According to the change in SBP from rest to EX (delta SBP), patients
      with HT were classified into two groups (group I, n = 12, delta SBP less than 72
      mmHg: group II, n = 8, delta SBP greater than or equal to 72 mmHg). There were no
      significant differences between the two groups with regard to SBP at rest, NE at
      rest and NE on EX. However, SBP at peak EX, delta SBP and the incidence of LVH
      were greater in group II than in group I. We conclude that exaggerated SBP
      response to EX in patients with HT is related to LVH.

PMID- 1387014
TI  - [A preliminary study on the red cell immune function in blood stasis syndrome in
      traditional Chinese medicine].
AB  - 20 patients with blood stasis syndrome (BSS), 20 patients with non-blood stasis
      syndrome (NBSS), and 17 normal subjects were measured by tests of RBC-C3b
      receptor rosette and RBC immune complex rosette. The rates of RBC-C3b receptor
      rosette formation (RBC-C3b RR, %) in BSS group, NBSS group and normal subjects
      were 20.90 +/- 4.02, 12.88 +/- 3.29 and 16.74 +/- 4.13 (P less than 0.01)
      respectively. The rates of RBC immune complex rosette formation (RBC-IC R, %) in
      the three groups were respectively 8.28 +/- 3.68, 7.73 +/- 2.48 and 7.41 +/- 2.43
      (P less than 0.05). RBC-C3b RR was correlated to RBC-IC R in the normal subjects
      (r = 0.695, P less than 0.001). In patients with the same disease, RBC-C3b RR
      between the two syndromes (BSS and NBSS) was also very significantly different (P
      less than 0.01). This study suggested that there are variations on red cell
      immune function in BSS patients, and also provided an evidence that different
      syndromes of traditional Chinese medicine exist in diseases.

PMID- 1387015
TI  - Ultracytochemical demonstration of Ca(++)-ATPase activity in the rat cardiac
      muscle.
AB  - Ca(++)-activated adenosine triphosphatase (Ca(++)-ATPase) was investigated in the
      rat cardiac muscle at neutral pH using tricine buffer. Reaction products
      indicating Ca(++)-ATPase activity were localized on the myocardial sarcolemma,
      sarcoplasmic reticulum, myofilaments, luminal and abluminal surfaces of capillary
      endothelium plasmatic membrane. The verification of the main enzymatic
      characteristics of Ca(++)-ATPase localization activity using this cytochemical
      procedure is under discussion.

PMID- 1387016
TI  - Molecular engineering of the antitumor immune response.

PMID- 1387017
TI  - Possible implication of B cell derived cytokines and sCD23 in the control of T
      lymphocyte development.

PMID- 1387018
TI  - Effect of CD23 on purified human hematopoietic cells.
AB  - We report herein the effect of soluble CD23 (sCD23) on the differentiation of
      lymphoid and myeloid precursors. CD23 is known as the low affinity receptor for
      IgE. In addition to it, our results indicate that sCD23 in synergy with IL1 is
      able to promote the maturation of normal and leukemic hematopoietic progenitor
      cells.

PMID- 1387019
TI  - Disadvantages of laparoscopic general surgery.

PMID- 1387020
TI  - Characterization of a novel aquaretic agent, OPC-31260, as an orally effective,
      nonpeptide vasopressin V2 receptor antagonist.
AB  - 1. OPC-31260, a benzazepine derivative, has been studied for its ability to
      antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver
      (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action
      of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal
      rats. 2. OPC-31260 caused a competitive displacement of [3H]-AVP binding to both
      V1 and V2 receptors with IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x
      10(-8) M, respectively. 3. OPC-31260 at doses of 10 to 100 micrograms kg-1, i.v.,
      inhibited the antidiuretic action of exogenously administered AVP in water
      loaded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not
      exert an antidiuretic activity suggesting that it is not a partial V2 receptor
      agonist. 4. After oral administration at doses of 1 to 30 mg kg-1 in normal
      conscious rats, OPC-31260 dose-dependently increased urine flow and decreased
      urine osmolality. The diuretic action of OPC-31260 was characterized as
      aquaresis, the mode of diuretic action being different from previously known
      diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5.
      The results indicate that OPC-31260 is a selective V2 receptor antagonist and
      behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the
      physiological role of AVP and in the treatment of various conditions
      characterized by water retention.

PMID- 1387021
TI  - Neuroendocrine response to clonidine and 8-OH-DPAT in rats following chronic
      administration of desipramine or sertraline.
AB  - 1. Rats were administered either desipramine (DMI) or sertraline daily at doses
      7.5 mg kg-1 or 10 mg kg-1, i.p., respectively and the effects on the functional
      state of hypothalamic neuroendocrine control mechanisms assessed by measurements
      of plasma hormones following acute drug challenge. The effects of treatment on
      gross behaviour and brain adrenoceptor density were also determined. 2. Both DMI
      and sertraline caused significant reduction in activity measured as ambulation
      and rearing at 14 days of treatment. 3. All animals were chronically cannulated
      after 14 days of treatment and tested for neuroendocrine response to acute i.v.
      clonidine (50 micrograms kg-1) or 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH
      DPAT, 250 micrograms kg-1) after 21 or more days of treatment. 4. Rats treated
      with DMI but not sertraline showed a virtually complete suppression of the growth
      hormone (GH) secretion elicited by clonidine in controls, while the secretion of
      corticosterone was augmented. 5. Treatment with DMI but not sertraline led to a
      significantly greater 8-OH-DPAT-induced secretion of prolactin than in the
      control rats, while the plasma concentrations of corticosterone following 8-OH
      DPAT were not influenced by either DMI or sertraline treatment. 6. The density
      (but not the affinity) of cerebral cortical binding of [3H]-dihydroalprenolol was
      significantly reduced by DMI treatment. 7. These results show that DMI treatment
      blunted the sensitivity of post-synaptic alpha 2-adrenoceptors, accompanied by
      complex interactions manifested as increased responsiveness of alpha 1
      adrenoceptors and 5-HT1A receptors. Sertraline had no significant neurendocrine
      effects at a dose which significantly reduced gross activity.

PMID- 1387022
TI  - Effects of monoamine uptake inhibitors on extracellular and platelet 5
      hydroxytryptamine in rat blood: different effects of clomipramine and fluoxetine.
AB  - 1. The concentration of 5-hydroxytryptamine (5-HT) in rat platelet-free plasma
      increased significantly 30 min after a single i.p. injection (10 mg kg-1) of each
      of six inhibitors of the high-affinity 5-HT uptake (fluvoxamine, fluoxetine,
      alaproclate, paroxetine, sertraline and clomipramine). The increases ranged from
      226% to 776% of control values. In contrast, imipramine, desipramine and
      femoxetine had no significant effect. The increase elicited by paroxetine was
      dependent on the dose (1, 5 and 10 mg kg-1) and returned to control values after
      4 h. That observed after clomipramine was also transient and paralleled the
      plasma concentration of the drug (Spearman-rank correlation r = 0.43). 2. In
      vivo, the rat pulmonary vascular endothelium removed trace amounts (8.8 nmol in a
      bolus) of intravenously injected [14C]-5-HT. Paroxetine pretreatment (10 mg kg-1,
      30 min before-hand) reduced this uptake by 73%. 3. Repeated fluoxetine treatments
      reduced rat whole blood 5-HT concentration (ca. -60% after daily 2 x 5 mg kg-1,
      i.p. during 14 days). However, plasma (extracellular) 5-HT was not increased. 4.
      Various repeated treatments with clomipramine (i.p. injections or osmotic
      minipumps, up to 30 mg kg-1 day-1), failed to decrease rat whole blood 5-HT
      concentrations. Platelet-free plasma 5-HT was also unchanged, even after
      treatments yielding plasma clomipramine levels 2.7 times higher than those that
      increased it acutely. 5. These results indicate that the extracellular pool of 5
      HT in rat blood (measured in the platelet-free plasma) is physiologically under
      the control of high-affinity 5-HT uptake systems.The sustained 5-HT uptake
      inhibition does not result in an increase of 5-HT in platelet-free plasma,
      suggesting that adaptative mechanisms are triggered. The distinct long-term
      effects of the two antidepressants clomipramine and fluoxetine on rat whole blood
      5-HT suggest a differential in vivo action on the rat 5-HT uptake.

PMID- 1387023
TI  - Effects of the neutral endopeptidase inhibitor, SQ 28,603, on regional
      haemodynamic responses to atrial natriuretic peptide or proendothelin-1 [1-38] in
      conscious rats.
AB  - 1. Regional haemodynamic responses to atrial natriuretic peptide (ANP, 0.5 nmol
      kg-1) or proendothelin-1 [1-38] (1.0 nmol kg-1) were assessed in the same
      conscious Long Evans rats before and 20 min after administration of the novel
      neutral endopeptidase (NEP) inhibitor, SQ 28,603 (50 mg kg-1, i.v.). In a
      separate experiment, responses to endothelin-1 (0.5 nmol kg-1), angiotensin I
      (0.25 nmol kg-1) and angiotensin II (0.12 nmol kg-1) were measured before and
      after administration of SQ 28,603. 2. SQ 28,603 alone had no significant
      cardiovascular effects but caused significant prolongation of the hypotensive,
      tachycardic and renal and mesenteric vasoconstrictor effects of ANP. However, the
      early vasodilator and late vasoconstrictor responses in the hindquarters were not
      affected significantly. 3. SQ 28,603 caused significant attenuation of the
      pressor effects of proendothelin-1 [1-38] but the associated bradycardia was
      unchanged. SQ 28,603 caused a significant inhibition of the renal and mesenteric
      vasoconstrictor effects of proendothelin-1 and also inhibited the initial
      vasodilator and subsequent vasoconstrictor responses in the hindquarters vascular
      bed. 4. SQ 28,603 had no significant effects on the haemodynamic responses to
      endothelin-1, angiotensin I, or angiotensin II. 5. The results are consistent
      with SQ 28,603 not only inhibiting NEP that is involved in the degradation of
      ANP, but also suppressing activity of the enzyme involved in the conversion of
      proendothelin-1 [1-38] to endothelin-1.

PMID- 1387024
TI  - Effects of cyclopiazonic acid, a novel Ca(2+)-ATPase inhibitor, on contractile
      responses in skinned ileal smooth muscle.
AB  - 1. Effects of cyclopiazonic acid (CPA), a specific inhibitor of the Ca(2+)-ATPase
      in sarcoplasmic reticulum (SR) of skeletal and cardiac muscles, on contractile
      responses induced by Ca(2+)-release from intracellular storage sites were
      examined in the longitudinal smooth muscle strip of the guinea-pig ileum skinned
      with beta-escin. 2. Ca(2+)-loading of storage sites (Ca(2+)-uptake) was performed
      in pCa 6.3 solution. The amount of Ca2+ taken up was monitored by use of the
      amplitude of contraction following application of 25 mM caffeine or 25 microM
      inositol 1,4,5-trisphosphate (IP3). 3. Contractile responses to caffeine or IP3
      were reduced or abolished when the preceding Ca(2+)-uptake was performed in the
      presence of 0.1-10 microM CPA. The dose of CPA required to inhibit the
      contraction induced by caffeine or IP3 by 50% was approximately 0.6 microM. The
      CPA-sensitive Ca(2+)-uptake completely depended upon the presence of ATP in the
      solution during Ca(2+)-uptake. 4. When 1 microM CPA was added after Ca(2+)
      uptake, the subsequent caffeine- or IP3-induced contraction was not significantly
      affected by the presence of CPA. 5. Acetylcholine-induced contraction was also
      almost abolished when the preceding Ca(2+)-uptake was performed in the presence
      of 10 microM CPA. 6. The relationship between pCa and contraction was not
      affected by the presence of 10 microM CPA in skinned fibres where Ca2+ storage
      sites had been destroyed by treatment with A23187. The enhancement of contraction
      in pCa 6.0 solution by calmodulin was not affected by 10 microM CPA.7. These
      results suggest that CPA selectively inhibits ATP-dependent Ca2"-uptake into
      intracellular storage sites in skinned ileal smooth muscle strips. CPA appears to
      be a potent, reversible, and very specific inhibitor of the Ca2+-pump in the
      storage sites of smooth muscle, and is an extremely valuable pharmacological
      tool.

PMID- 1387026
TI  - Pharmacological characterization of 5-hydroxytryptamine-induced excitation of
      afferent cervical vagus nerve in anaesthetized rats.
AB  - 1. An excitatory response to 5-hydroxytryptamine (5-HT) was measured from the
      afferent vagus nerve of anaesthetized rats. Measurements were determined by an
      extracellular recording from the whole nerve. 2. Intravenous bolus injection of 5
      HT (1.56-100 micrograms kg-1) evoked a dose-dependent excitation of afferent
      vagus nerve activity. This response was blocked not only by a selective 5-HT3
      receptor antagonist, GR38032F (10 and 100 micrograms kg-1), but also by a 5-HT2
      receptor antagonist, ketanserin (10 and 100 micrograms kg-1). 3. Both a 5-HT3
      receptor agonist, 2-methyl-5-HT (3.12-100 micrograms kg-1), and a 5-HT2 receptor
      agonist, alpha-methyl-5-HT (3.12-50 micrograms kg-1), produced a dose-dependent
      excitation of afferent vagus nerve activity. These excitatory effects were
      antagonized by GR38032F (10 micrograms kg-1) and ketanserin (10 micrograms kg-1),
      respectively. 4. A 5-HT1 like receptor agonist, 5-carboxamidotryptamine (50
      micrograms kg-1), and a putative 5-HT4 receptor agonist, 5-methoxytryptamine (100
      micrograms kg-1), failed to produce excitatory effects on the afferent vagus
      nerve. 5. These results suggest that the 5-HT-induced excitatory response of the
      afferent vagus nerve might be mediated not only via 5-HT3 receptors but also via
      5-HT2 receptors in anaesthetized rats. It is unlikely, however, that either 5-HT1
      like or putative 5-HT4 receptors are involved in the excitatory response of the
      afferent vagus nerve to 5-HT.

PMID- 1387025
TI  - Effects of vapiprost, a novel thromboxane receptor antagonist, on thrombus
      formation and vascular patency after thrombolysis by tissue-type plasminogen
      activator.
AB  - 1. A thrombus was induced in the rat femoral artery by endothelial damage due to
      the photochemical reaction between systemically-injected Rose Bengal and
      transillumination with green light (wavelength: 540 nm). The artery of the
      control rat was completely occluded in 302.8 +/- 27.0 s after the initiation of
      the reaction. 2. Pretreatment with vapiprost (0.1, 0.3 and 1.0 mg kg-1, i.v., 5
      min before the reaction) prolonged the time required to occlude the femoral
      artery in a dose-dependent manner. The efficacy of vapiprost on the time required
      for occlusion was over 10 times higher than that of aspirin which was
      administered 30 min before the reaction. 3. The thrombolytic effects of tissue
      type plasminogen activator (tPA) on the established arterial thrombus in the
      presence and absence of vapiprost were also studied in the same model. When
      vapiprost (0.3 mg kg-1, i.v.) was administered just before tPA infusion (100
      micrograms kg-1 min-1 for 30 min), the time required to reperfuse the occluded
      artery was reduced, the incidence of the reperfusion was increased and the
      arterial blood flow after reperfusion was improved. 4. When vapiprost (1.0 mg kg
      1 daily p.o.) was administered for 1 week after the establishment of reperfusion
      by tPA combined with vapiprost, the patency of the reperfused artery was improved
      and the femoral arterial blood flow was better preserved than after treatment
      with only tPA. 5. These findings suggest that this thromboxane receptor
      antagonist may be a useful adjunct to anti-thrombotic therapy. The combination
      therapy with tPA may be more effective than treatment with tPA alone and provides
      greater protection against reocclusion after reperfusion.

PMID- 1387028
TI  - Effects of interleukin-1 receptor antagonist on the behavioral effects of
      lipopolysaccharide in rat.
AB  - To investigate the role of interleukin-1 (IL-1) in lipopolysaccharide (LPS)
      induced sickness behavior, rats were injected with recombinant human interleukin
      1 receptor antagonist (IL-1ra), an endogenous cytokine able to block most of the
      biological effects of IL-1 both in vivo and in vitro. Intraperitoneal injection
      of IL-1ra (3 mg/rat) attenuated the depressive effect of LPS (250 micrograms/kg)
      on social exploration and body weight when both treatments were injected
      peripherally. Intracerebroventricular injection of IL-1ra (60 micrograms/rat) did
      not block the effects of peripherally injected LPS. These data indicate that the
      peripherally mediated effects of IL-1 account for a significant part of LPS
      induced sickness behavior.

PMID- 1387027
TI  - Evidence for postsynaptic mediation of the hypothermic effect of 5-HT1A receptor
      activation.
AB  - 1. The 5-HT1A ligand BMY 7378 (8-[2[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]8
      azaspirol [4,5]-decane-7,9-dione dihydrochloride, 0.032-2 mg kg-1, s.c.) caused
      hyperphagia, a response to the activation of presynaptic 5-HT1A receptors. 2. BMY
      7378 (8 mg kg-1, s.c.) and the 5-HT1A agonist (8-hydroxy-2-(di-n-propylamino)
      tetralin (8-OH-DPAT), 0.10 and 0.25 mg kg-1 s.c.) also caused hypothermia. This
      was inhibited by (-)-pindolol (1-mg kg-1, i.p.) and not prevented by
      pretreatments with p-chlorophenylalanine which grossly depleted 5
      hydroxytryptamine (5-HT) from terminal regions. The hypothermic effects are
      explicable by activation of postsynaptic 5-HT1A receptors. Infusion of BMY 7378
      (8-64 micrograms) into the dorsal raphe was without convincing hypothermic
      effect. 3. BMY 7378 (8 mg kg-1, s.c.) inhibited another effect of activation of
      postsynaptic 5-HT1A receptors, i.e., the induction of components of the 5-HT
      syndrome by 8-OH-DPAT (0.5, 1.0 mg kg-1, s.c.) which suggests that BMY 7378 has
      antagonistic as well as agonistic effects at these sites. 4. Partial agonist
      properties of BMY 7378 at postsynaptic sites were also indicated by doses for
      hypothermia being much greater than those for hyperphagia i.e., ED50
      (hypothermia) greater than 2 mg kg-1, ED50 (hyperphagia) = 0.010 mg kg-1. This
      contrasts with the similar ED50 values for both the hypothermic (ED50 = 0.08-0.10
      mg kg-1) and hyperphagic (ED50 = 0.06-0.10 mg kg-1) effects of 8-OH-DPAT.5. The
      evidence obtained for mediation of the hypothermic response to 5-HTIA agonists by
      postsynaptic sites is relevant to the interpretation of the effects on it of
      antidepressant treatments and depressive illness.

PMID- 1387029
TI  - The combination of NMDA antagonism and morphine produces profound antinociception
      in the rat dorsal horn.
AB  - Dorsal horn nociceptive neurones exhibit wind up, a frequency dependent
      potentiation of their responses to repeated C-fibre stimulation. Intrathecal
      morphine (5 micrograms) significantly reduces the initial responses of the
      neurones but not wind up whereas the reverse is true for N-methyl-D-aspartate
      (NMDA) antagonists. The combination of intrathecal morphine (5 micrograms) and 7
      chlorokynurenate (2.5 micrograms), an antagonist at the glycine site of the NMDA
      receptor, abolishes both the input and wind up of these neurones.

PMID- 1387030
TI  - Cocaine-induced behavioral sensitization and D1 dopamine receptor function in rat
      nucleus accumbens and striatum.
AB  - Based on electrophysiological data showing that repeated cocaine administration
      produces persistent enhancement of D1 dopamine (DA) receptor-mediated responses
      in nucleus accumbens (NAc), we investigated whether changes in neurochemical
      properties of these receptors resulted when rats were injected with cocaine (15
      mg/kg) for 6 days followed by a 7-day abstinence period. D1 DA receptor density
      and affinities for either [3H]SCH 23390 or DA were similar between NAc and
      striatum and between saline and cocaine treatment groups. DA-stimulated adenylyl
      cyclase activity was 1.5-fold higher in striatum than in NAc; however, repeated
      cocaine treatment produced no persistent changes in enzyme activity in either
      brain area.

PMID- 1387031
TI  - Autoradiographic localization of dopamine D1 and D2 receptors in rat cerebral
      cortex following unilateral neurotoxic lesions.
AB  - Relative to dopaminergic innervation of cortex, dopamine D1 and D2 receptors may
      be located on presynaptic terminals and/or postsynaptically on cortical neurons.
      To assess the relative distribution of these sites, quantitative in vitro
      receptor autoradiography was performed following injection of 6-hydroxydopamine
      (6-OHDA) into the median forebrain bundle (MFB; which lesions presynaptic DA
      terminals) and ibotenic acid into the prefrontal and anterior cingulate cortices
      (which lesions neurons whose cell bodies are intrinsic to cortex). Receptor
      autoradiography was performed ten days after injection of neurotoxins with
      [3H]SCH 23390 (a D1 probe) and [125I]epidepride (a D2 probe). Both DA receptor
      subtypes were found in all layers of anterior cingulate and prefrontal cortices
      but were concentrated in deeper layers V and VI. Ibotenic acid lesion of cortex
      reduced D1 and D2 receptors by 55-80%, although the concentrations of DA and its
      major metabolite dihydroxyphenylacetic acid (DOPAC) were unchanged. Lesion of MFB
      produced no significant change in D1 and D2 receptors, but was associated with a
      49-52% decrease in DA and DOPAC levels relative to the contralateral side. These
      results suggest that the majority of D1 and D2 receptors in prefrontal and
      anterior cingulate cortices are located postsynaptically on neurons intrinsic to
      the cortex.

PMID- 1387032
TI  - D1 and D2 receptor modulation in rat striatum and nucleus accumbens after
      subchronic and chronic haloperidol treatment.
AB  - The antipsychotic effects of neuroleptic drugs are believed to be achieved by
      chronic blockade of dopaminergic transmission in the limbic system. Nevertheless,
      the effects of chronic (3-12 months) haloperidol administration on the
      dopaminergic transmission in the nucleus accumbens of rodents remains poorly
      understood. Studies of spontaneous locomotor activity (SLA), a behavioral measure
      related to limbic dopamine transmission, and of dopamine D2 receptor density in
      the nucleus accumbens after chronic oral haloperidol treatment have yielded
      conflicting results. We evaluated these indices after 8 months of parenteral
      administration of haloperidol decanoate. We report here that, after 8 months of
      parenteral treatment, SLA stays significantly decreased and D2 receptors in the
      nucleus accumbens exhibit the same up-regulation as in the striatum (about 50%).
      These results fail to support the notion of a different pattern of D2 receptor
      adaptation to neuroleptic treatment between the nucleus accumbens and the
      striatum. In contrast, dopamine D1 receptors were found to be unaffected in the
      nucleus accumbens but decreased in the striatum by 22% after 8 months of
      treatment. This observation could be relevant to the pathogenesis of tardive
      dyskinesia.

PMID- 1387033
TI  - Post-lesion administration of the NMDA receptor antagonist MK-801 does not impair
      motor recovery after unilateral sensorimotor cortex injury in the rat.
AB  - Although treatment with N-methyl-D-aspartate (NMDA) receptor antagonists reduce
      neuronal loss after cerebral infarction and brain trauma in laboratory animals,
      there is little data concerning the effects of these drugs on behavioral
      recovery. Because NMDA receptor antagonists impede certain kinds of learning, and
      because motor recovery after sensorimotor cortex injury in the rat is dependent
      on post-lesion experience, we hypothesized that treatment with MK-801 after focal
      brain injury would be detrimental. Groups of rats were first trained to traverse
      a narrow elevated beam and then subjected a right sensorimotor cortex suction
      ablation lesion. In the first experiment, 24 h later, each rat received a single
      dose of either saline or the NMDA receptor antagonist MK-801 (0.5, 1.0, or 2.0
      mg/kg). Beam-walking recovery was measured over the next 12 days. In a second
      experiment, rats were given 3 doses of MK-801 (0.5 mg/kg) at 24 h intervals
      beginning 24 h after cortex injury. In a third experiment, lesioned and sham
      operated rats were allowed to recover for 12 days and then given MK-801 (0.5
      mg/kg). Despite obvious behavioral effects of the drug, there was no overall
      difference in beam-walking performances among the treatment groups in any of the
      experiments. If 're-learning' is involved in motor recovery after cortex injury,
      the present results suggest that the process is not susceptible to permanent
      disruption by the early or late administration of an NMDA receptor antagonist.

PMID- 1387034
TI  - A comparison of the effects of the 5-HT1 agonists TFMPP and RU 24969 on feeding
      following peripheral or medial hypothalamic injection.
AB  - Experiments were conducted to compare the food intake suppressant effects of the
      5-hydroxytryptamine (5-HT)1 agonists 1-3-trifluoromethylphenylpiperazine
      hydrochloride (TFMPP) and 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H indole (RU
      24969) following either peripheral or medial hypothalamic injections. The effects
      of these manipulations were examined in 3 different paradigms involving the
      stimulation of feeding by: (1) infusion of 25 nmol noradrenaline (NA) into the
      medial hypothalamus, (2) adaptation to a 20 h food deprivation schedule, and (3)
      the presentation of a palatable wet mash diet for 1 h each day to ad libitum-fed
      rats. In all 3 paradigms TFMPP and RU 24969 (0.31-5 mg/kg, i.p.) induced dose
      dependent reductions of food intake. Both drugs were somewhat less potent at
      inhibiting feeding that resulted from food deprivation. In contrast to these
      results medial hypothalamic infusion of TFMPP or RU 24969 (12.5-50 nmol) failed
      to affect food intake in any of the 3 tests. This occurred in spite of the fact
      that both 5-HT (12.5-50 nmol) and fluoxetine (12.5-50 nmol) mildly attenuated the
      feeding that resulted from NA infusion into the same site. The results provide
      clear evidence that the food intake suppressant effects of peripherally injected
      TFMPP and RU 24969 are not mediated in the medial hypothalamus. They also suggest
      that even though manipulations of serotonergic function within the medial
      hypothalamus can alter food intake, this probably does not involve selective
      activation of 5-HT1C and/or 5-HT1B receptors.

PMID- 1387035
TI  - Reduced density of NMDA receptors and increased sensitivity to dizocilpine
      induced learning impairment in aged rats.
AB  - About 20 min prior to training in a shock-motivated 14-unit T-maze, young (3-4
      months) and aged (24-25 months) male Fischer-344 rats were given s.c. injections
      of either saline or dizocilpine (MK-801, 0.02 or 0.04 mg/kg), a non-competitive
      antagonist of the N-methyl-D-aspartate (NMDA) receptor. The aged rats showed a
      dose-dependent impairment in maze performance. Deficiencies were manifested as
      increases in errors, in runtime from start to goal, and in the number and
      duration of shocks received. In contrast, young rats exhibited no detrimental
      effects of dizocilpine on maze performance. Analysis of [3H]glutamate binding in
      these rats revealed a marked age-related decline in NMDA receptor binding in
      hippocampus. A significant correlation was observed between errors in the maze
      and hippocampal [3H]-glutamate binding, but the correlation was positive, i.e.,
      rats that made the most errors had the highest level of NMDA receptor binding.
      Thus, compared to young rats, aged rats were more sensitive to the behavioral
      effects of NMDA receptor antagonism and they showed a hippocampal loss of
      [3H]glutamate in binding, which may be related to the increased sensitivity to
      dizocilpine. The positive correlation between poor maze performance and NMDA
      receptor binding suggests that the behaviors assessed involve complex
      interactions between NMDA receptors and other neuronal systems in the
      hippocampus.

PMID- 1387037
TI  - Decreased brain N-acetylaspartate in Huntington's disease.
AB  - The concentration of N-acetylaspartic acid (NAA) was measured in perchloric acid
      extracts of postmortem brain tissue obtained from patients with Huntington's
      disease and from control subjects. The material in the desalted extracts was
      resolved on an ion exclusion column and the content of NAA was determined by
      subsequent fluorometric quantitation of aspartate in hydrolyzates of the resolved
      NAA. The concentration of NAA in the putamen from patients with Huntington's
      disease was less than half that of controls (2.74 vs. 6.06 mumol/g wet weight). A
      smaller but significant reduction was also evident in samples of cerebral cortex
      from Brodmann area 10 (3.99 vs. 5.29 mumol/g), while the difference in
      concentrations in the cerebellum was not statistically significant. Though NAA
      could play a direct role in Huntington's disease, it seems more likely that the
      changes observed reflect illness or death of neurons, and that it may be feasible
      to monitor the course of Huntington's disease from NAA determinations. The same
      tissue extracts were also examined for the presence of D-isomers of amino acids.
      Only traces were found in NAA, aspartate, or glutamate.

PMID- 1387036
TI  - Impairment of endothelium-dependent dilatation of the basilar artery during
      diabetes mellitus.
AB  - The goal of this study was to determine whether responses of the basilar artery
      are altered during diabetes mellitus. We measured the diameter of the basilar
      artery in vivo in non-diabetic and diabetic rats (streptozotocin; 50-60 mg/kg
      i.p.). Responses of the basilar artery to agonists, which presumably produce
      dilatation by releasing endothelium-derived relaxing factor (EDRF), were impaired
      in diabetic rats compared to non-diabetic rats. Acetylcholine (1.0 and 10 microM)
      dilated the basilar artery by 13 +/- 2 and 26 +/- 4% (means +/- S.E.M.),
      respectively, in non-diabetic rats, but by only 4 +/- 1 and 9 +/- 2%,
      respectively, in diabetic rats (P less than 0.05). Bradykinin (1.0 and 10 microM)
      dilated the basilar artery by 14 +/- 2 and 35 +/- 6% (means +/- S.E.M.),
      respectively, in non-diabetic rats, but by only 5 +/- 1 and 6 +/- 2%,
      respectively, in diabetic rats (P less than 0.05). The response to nitroglycerin
      was similar in non-diabetic and diabetic rats. Thus, impairment of vasodilatation
      in diabetic rats in response to acetylcholine and bradykinin is not related to
      non-specific impaired of vasodilatation. Next, we examined the possibility that
      impaired dilator responses of the basilar artery in response to acetylcholine and
      bradykinin in diabetic rats may be related to the activation of the thromboxane
      A2-prostaglandin H2 receptor. SQ 29548 (a specific thromboxane A2-prostaglandin
      H2 receptor antagonist) did not alter responses of the basilar artery to
      acetylcholine and bradykinin. These findings suggest that diabetes mellitus
      impairs endothelium-dependent dilatation of the basilar artery.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1387038
TI  - Effects of the N-methyl-D-aspartate antagonists on the rise in [Ca2+]i following
      depolarization in aged rat brain synaptosomes.
AB  - The effects of non-competitive NMDA antagonists, MK-801 and dextrorphan in
      relation to the rise in intracellular Ca2+ concentrations ([Ca2+]i) after
      stimulation with 15 mM K+ in whole brain synaptosomes from young (3 months old)
      and aged (24 months old) Fisher344 rats were examined. A fluorescent chelating
      agent, Rhod-2, was employed to monitor any alterations of K(+)-evoked [Ca2+]i. In
      young rats, the rise in [Ca2+]i following depolarization was affected by neither
      dextrorphan (1, 10, 100 microM) nor MK-801 (0.1, 1, 10 microM), while in aged
      rats, 1 microM dextrorphan and 0.1 microM MK-801 brought about a significant
      increase in [Ca2+]i following depolarization. In low Mg2+ medium, 10 microM MK
      801 and 100 microM dextrorphan significantly inhibited the rise in [Ca2+]i after
      stimulation with 15 mM K+ in young rats, while neither dextrorphan nor MK-801
      could affect the rise in [Ca2+]i significantly in aged rats. When 100 microM NMDA
      was applied in a medium containing 1.2 mM Mg2+, the rise in [Ca2+]i following
      depolarization was slightly inhibited by 1 microM MK-801 in young rats, but it
      was not inhibited significantly by dextrorphan. In aged rats, both 100 microM
      dextrorphan and 10 microM MK-801 strongly inhibited the rise in [Ca2+]i following
      depolarization in the presence of 100 microM NMDA. Instead of NMDA, when 100
      microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), a non
      NMDA receptor agonist, was applied, dextrorphan did not inhibit the rise in
      [Ca2+]i. In low Mg2+ medium, 100 microM NMDA potentiated the inhibitory effect of
      10 microM dextrorphan in young rats, while 100 microM dextrorphan or MK-801 did
      not show any further inhibition by adding 100 microM NMDA. The addition of 100
      microM AMPA did not affect the effect of dextrorphan in a low Mg2+ medium in
      young rats. These results suggest that NMDA antagonist-mediated [Ca2+]i
      homeostatic system may alter through aging. In addition, the findings that NMDA
      potentiated the inhibitory effect of NMDA antagonist, which being further
      potentiated by aging or lowered extrasynaptosomal Mg2+, indicate the possibility
      that the Mg2+ block to NMDA receptors might be attenuated through aging.

PMID- 1387039
TI  - Assessment of the need for education and/or training in the dental care of people
      with handicaps.
AB  - A survey questionnaire was sent to members of the British Society of Dentistry
      for the Handicapped to investigate their opinions about the need for education
      and training of dentists in the delivery of oral care to people with handicaps.
      Their educational experience was explored. Views on education and training were
      investigated in relation to timing, content and methods. Three hundred and sixty
      five questionnaires were sent and the total response rate was 67.4 per cent.
      There was a higher percentage of females than males and a higher percentage of 30
      to 39 year old subjects in the sample. The data were analysed using the 'Survey
      Plus' program. A high proportion of respondents thought there was a need for
      education and training of dentists in the delivery of care to people with
      handicaps (70 per cent). Their views on training provided information on three
      main issues: the type of training course, and the content and methods of training
      or education. In-service training, observation of other dentists and continuing
      education courses were opportunities that people considered would have helped
      them. Although views varied, there was a notable desire for contact with
      experienced clinicians, particularly the observation of them carrying out
      treatment, the opportunity for participating in teaching methods, discussions and
      problem-solving aids. The involvement of carers and of people with handicaps
      themselves was suggested. Undergraduate and postgraduate education were both
      considered important, although postgraduate training was the more highly
      favoured. In relation to the content of training, behaviour management,
      communication skills and appropriate treatment planning were most commonly
      identified. This information will be useful for those wishing to establish
      courses.

PMID- 1387040
TI  - Treatment accessibility for physically and mentally handicapped people--a review
      of the literature.
AB  - This paper presents a review of the literature concerning the access of
      physically and mentally handicapped people to dental care, and the attitudes of
      dentists towards them. It is particularly concerned with access for those who are
      housebound, or restricted to wheelchairs. Accessible dental care facilities and
      information about them may have been difficult to locate in the United Kingdom.
      This situation may improve in the near future as family health services
      authorities have data obtained from dentists registering with them under the new
      National Health Service contract, and general dental practice leaflets are
      required to provide information on wheelchair access. Transport systems may
      severely limit the ability of some handicapped people to travel to otherwise
      accessible surgeries. Professional and societal attitudes towards handicapped
      people are ambivalent. It has been shown that professional attitudes towards
      handicapped people, and willingness to treat them, increases with training in
      this field. At present, this training has a low priority in many dental schools.

PMID- 1387041
TI  - The influence of terfenadine and ipratropium bromide alone and in combination on
      bradykinin-induced nasal symptoms and plasma protein leakage.
AB  - Nasal instillation of bradykinin elicits many of the characteristic features of
      rhinitis. To assess the relevance of histamine release from metachromatic cells
      and the activation of cholinergic pathways, we investigated the effects of
      terfenadine, a histamine H1-receptor antagonist, and ipratroprium bromide, a
      selective antimuscarinic agent, on bradykinin induced rhinorrhoea, nasal airways
      resistance (NAR), nasal pain and plasma protein leakage. Oral terfenadine (120
      mg) or matched placebo and nasal ipratropium bromide (80 micrograms) or matched
      placebo were administered at 4 hr and 30 min respectively prior to bradykinin
      nasal challenge in two randomized, double-blind and cross-over studies on eight
      non-rhinitic subjects. Thus subjects received either double-placebo, oral
      terfenadine and nasal placebo, oral placebo and nasal ipratopium bromide or oral
      terfenadine and nasal ipratropium bromide, as pretreatment. Bradykinin challenge
      induced mean maximal increases of 57%, 59%, 77% and 72% in NAR on the placebo,
      terfenadine, ipratropium bromide and terfenadine plus ipratropium bromide
      pretreatment days respectively. These increments were not significantly
      different. Similarly rhinorrhoea and nasal pain induced by bradykinin nasal
      challenge were not significantly different on the four challenge days. Bradykinin
      nasal challenge caused a mean maximal increase in albumin levels in recovered
      nasal lavages of 11.5, 13.0, 12.2 and 12.3 times of baseline levels on the
      placebo, terfenadine, ipratropium bromide and terfenadine plus ipratroprium
      bromide pretreatment days respectively. Similarly total protein levels achieved a
      mean maximal increase of 8.0, 8.2, 7.9 and 8.8 times of baseline levels on these
      challenge days. The increments in both albumin and total protein did not
      significantly differ on the 4 challenge days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387042
TI  - Oral care for the homebound and institutionalized.
AB  - Most patients who are homebound or in LTC facilities have multiple health
      problems that require the cooperation of many different types of providers.
      Dentists have a specific role in this process because they can improve the
      quality of life for the elderly by keeping them free of oral infection, restoring
      their dentition so they can enjoy eating, and restoring facial esthetics. It
      should be apparent that dental care for these patients is a complicated process.
      There are many considerations in prescribing the type of treatment needed by each
      patient. These include the patient's life span, medical history, drug history,
      mental status, mobility status, neuromuscular coordination, dental status,
      previous dental experience, dental expectations, and economic status. This
      information must be gathered by the dentist from the patient, the family, the
      nursing staff, and the patient's physician. Furthermore, the dentist also must
      assess the facilities and equipment available to carry out oral health care. Only
      after such considerations can a dental treatment plan evolve that is appropriate
      for the individual concerned. Dental care for one patient may be no treatment
      whatsoever, whereas a different patient in the same institution may require the
      most technologically sophisticated care that dentistry has to offer. Finally, the
      following circumstances should suggest that a homebound or institutionalized
      patient needs an urgent oral/dental evaluation: General Signs and Symptoms;
      Orofacial pain, Visible oral infection, Difficulty chewing food, Halitosis/dry
      burning mouth, Visible oral soft tissue lesions (white, red, or ulcerated). Tooth
      related signs and symptoms; Visible dental decay, Loose or mobile teeth, Bleeding
      or sore gums. Denture-related Signs and Symptoms; Loose, ill-fitting, or worn
      dentures, Missing denture teeth, Home repairs attempted.

PMID- 1387043
TI  - [Changes in left ventricular filling after acute increase of afterload in
      essential arterial hypertension with or without left ventricular hypertrophy].
AB  - It is debatable whether a direct causal link exists between left ventricular
      hypertrophy (LVH) and abnormal left ventricular filling (LVF) in arterial
      hypertension (AH). To assess if LVH is responsible for peculiar patterns of LVF,
      we examined 30 selected subjects, similar in age and body surface area, by
      Doppler echocardiography: 10 hypertensives (SBP: 158 +/- 15; DBP: 105 +/- 7 mmHg)
      with LVH (IM: 154 +/- 19 mg/m2) (Group 1); 10 hypertensives (SBP: 157 +/- 9; DBP:
      101 +/- 5 mmHg) without LVH (IM: 105 +/- 17 mg/m2; Group 2); 10 normotensives
      without familiar history of AH (Group 3). LVF was analyzed in baseline conditions
      and during transient afterload increase, obtained by isometric exercise
      (handgrip, HG, for 5 min at 30% of maximal effort). At rest: 1) A wave peak
      velocity resulted significantly higher (p less than 0.01) in Group 1 (61 +/- 3
      cm/s) versus Group 3 (52 +/- 7 cm/s), and E wave peak velocity was significantly
      lower in Group 1 (58 +/- 13 cm/s) versus Group 3 (74 +/- 10 cm/s); 2) Group 2
      values (E wave: 66 +/- 12; A wave: 58 +/- 15 cm/s) were intermediate between
      those of groups 1 and 3, and with no significant differences; 3) E/A ratio
      resulted significantly lower both in Group 1 (1.04 +/- 0.2) and Group 2 (1.21 +/-
      0.2) versus Group 3 (1.6 +/- 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387044
TI  - Contraceptives and cancer--looking for the evidence.

PMID- 1387045
TI  - [Giardiasis in dog and cat owners].
AB  - In subjects with positive giardiasis tests examinations of contacts were made not
      only in all members of the family but also in dogs and cats living with them in
      the same household. Attention was paid to the possible transmission of giardias.
      A total of 174 families were examined, i.e. 1140 subjects incl. 156 positive
      ones. Of 123 examined dogs 9 were positive and of 56 cats 8 were positive. Forty
      three dog keepers were negative, of their 222 dogs 60 were positive. Although no
      association was proved between the infection of domestic animals and humans in
      the examined group, it is recommended to treat not only humans but also domestic
      animals.

PMID- 1387046
TI  - [Use of the Streptotest for identification of enterococci and viridans-type
      streptococci].
AB  - The new identification system STREPTOtest (fy. Lachema, Brno) was evaluated. A
      total 118 well-known strains of genus Enterococcus, Streptococcus, Aerococcus,
      Stomatococcus and Gemella were tested. The STREPTOtest system rapidly and
      reliably distinguished genus Enterococcus from genus Streptococcus. This method
      identified correctly to the species level 65.9% of enterococci strains and 52.5%
      of streptococci strains. The STREPTOtest was used for identification of A.
      viridans and S. mucilaginosus and it was possible to separate these strains from
      similar ones. A new differentiation chart for identification of all 13 recently
      described enterococcal species was proposed.

PMID- 1387047
TI  - [Review of new methods of investigating cellular immunity].
AB  - The objective of this review is to describe some recent methods which are used to
      examine the specific and non-specific cellular defense of the body. Greatest
      attention is devoted to methods which are not mentioned in the publication
      "Selected diagnostic methods in medical immunology" by J. Prochazkova (Prague,
      Avicenum 1986). The article summarizes data from the literature on recent
      examination methods of various parameters of cellular immunity such as detection
      of surface membrane antigens of immunocompetent cells, examination of cytotoxic
      activity, blastic transformation and activation of cells of the immune system.

PMID- 1387048
TI  - [Vaccination against tick-borne encephalitis in the Central Slovakia Region using
      a Soviet vaccine].
AB  - During the period between 1986 and 1989 in the region 1311 people working in
      forestry were vaccinated against tick-borne encephalitis by the inactivated
      Soviet vaccine. Only some of the people had prevaccination examinations only in
      some reactogenity of the vaccine was investigated as well as the persistence of
      humoral antibodies one and two years after the basic vaccination. These
      examinations in some of the vaccinated subjects were made in autumn 1986 and
      spring 1987. After two doses of vaccine in the haemagglutination-inhibition test
      (HIT) the seroconversion was 77% (of 182 evaluated) with a geometric mean of
      37.9. One year after the primary vaccination in 53% of the examined subjects the
      titre of humoral antibodies dropped to negative values. Two years after the
      primary vaccination in the HIT antibodies were detected in 44% of 57 examined
      subjects. None of the immunized subjects contracted tick-borne encephalitis.

PMID- 1387049
TI  - [New findings on alpha-hemolytic strains of E. coli in urinary tract infections.
      II. Antigen structure, resistance, production of colicins and siderophores].
AB  - Alphahaemolytic uropathogenic strains of E. coli (UPEC) belong mostly into the
      serogroup 04, 06, 018 and 075. UPEC are resistant against antibacterial
      substances and against the bactericide action of serum. Properties which
      condition the virulence of these strains are also colicin and siderophore
      production.

PMID- 1387050
TI  - [An explosive familial epidemic of viral hepatitis B with a horizontal
      transmission].
AB  - The authors describe the course of an explosive epidemic of viral hepatitis B
      (VHB) where all members of a seven-member family contracted the disease. The
      probable source of infection was an infant with a history of anicteric VHB with
      transition into chronicity and with HBs and HBe antigenaemia. Four members of the
      family contracted the disease between the 126th and 172nd day after his return
      from hospital to the family and another two members of the family contracted the
      disease three months later. Generally accepted risk factors for transmission of
      VHB could be ruled out. Saliva is suspected as a transfer factor of the disease.
      Five children had the anicteric form of VHB with an atypical but protracted
      course, in two with probable development of a chronic character of the disease.
      Adult patients had the icteric form of the disease. All cases were diagnosed by
      biochemical examination and confirmed by a positive finding of HBsAg and/or a
      positive finding of anti HBs antibodies.

PMID- 1387051
TI  - [Prevalence of hantavirus infection in small mammals in the South Moravian
      Region].
AB  - In 1987 to 1990 in the South Moravian region 1094 lungs of small terrestrial
      mammals were examined for hantavirus antigen and sera of 525 rodents and 93 hares
      for antibodies against these viruses. In the majority the materials were not from
      the same individual. Lungs were examined by the ELISA method, antibodies were
      assessed by the indirect immunofluorescence reaction. An antigen resembling the
      western subtype (Puumala) was found in 65 animals (5.9%) of two rodent species
      (Microtus arvalis--63 times and Apodemus flavicollis--twice) in 20 localities.
      Antibodies against this subtype were detected in 25 examined individuals (4.0%)
      of four species (Microtus arvalis, Apodemus flavicollis, Pitymys subterraneus and
      Lepus europaeus) from eight localities. A marked predominance of positive
      findings was obtained from Microtus arvalis which under conditions of the South
      Moravian region can be considered the main host of hantaviruses of the western
      subtype. Only in one specimen of Clethrionomys glareolus from Hrbov antibodies
      against the eastern subtype were detected (Hantaan). Hantaviruses form in
      Southern Moravia natural foci of the avector type, in particular in perennial
      fodder crops, most frequently with a mesophil character of the site. The foci
      were found most frequently at sites of assumed borderlines of natural meadow
      forests of the Alno-Padion type and woods of the Carpinion betuli, Quercion
      robori-petreae and Fagion silvaticae type.

PMID- 1387052
TI  - Quantitative analysis of factors contributing to handicap and distress in
      vertiginous patients: a questionnaire study.
AB  - Statements encapsulating common beliefs, behaviour and difficulties associated
      with vertigo, derived from in-depth interviews, were used to construct a Vertigo
      Handicap Questionnaire (VHQ) which was completed by 84 patients referred for
      vestibular testing. Factor analysis identified four principal components of
      handicap in addition to 'Anxiety and Depression', (which was isolated prior to
      analysis): 'Restriction of Activities', both physical and social; concern that
      vertigo would adversely affect social relationships ('Social Anxieties'); 'Fear
      of Vertigo', both the attacks themselves and their possible significance; and
      'Severity of Attacks' which was multiplied with frequency of attacks to give a
      measure of reported physical disability. Multiple regression revealed that
      Severity x Frequency of attacks contributed to patient distress only indirectly,
      through its influence on the mediating psychological and behavioural variables.
      Significant patient benefit may therefore result from counselling or behavioural
      therapy, whether or not the vertigo itself can be controlled.

PMID- 1387054
TI  - Physician employers and the Americans With Disabilities Act: are you ready?

PMID- 1387053
TI  - Acute subendocardial infarction with diffuse intense Tc-99m PYP uptake and
      minimal Tl-201 abnormality.
AB  - Tc-99m PYP scintigraphy performed on a patient with severe anterior chest pain
      showed diffuse intense uptake with central decreased activity corresponding to
      the left ventricular cavity. Tl-201 myocardial perfusion scintigraphy at rest
      revealed a minimal perfusion abnormality with decreased apical uptake in the
      lateral view. Because of these findings, diffuse subendocardial infarction was
      suggested.

PMID- 1387055
TI  - [The association of amlodipine with isosorbide-5-mononitrate in the treatment of
      ischemic-hypertensive cardiopathy].
AB  - Every form of therapy must always aim at obtaining maximum benefit with minimum
      use of drugs; also for the purpose of ensuring maximum patient compliance. With
      this end in mind, 21 patients with ischemic heart disease and arterial
      hypertension were divided into three groups of seven subjects each and submitted
      to different drug treatments with single daily doses: group 1 received isosorbide
      5-mononitrate (60 mg), group 2 amlodipine (10 mg), and group 3 a combination of
      both drugs at the same dosage, for four weeks. Statistical analysis showed blood
      pressure values to have been significantly reduced in subjects receiving
      amlodipine both alone and in combination (p less than 0.05) while no significant
      variation was observed (p = n.s.) in those treated with isosorbide-5-mononitrate
      only. A significant reduction of diastolic blood pressure (p less than 0.05)
      occurred only in patients talking the combination. No significant changes of
      heart rate (p = n.s.) were observed in any of the groups. Tests at the cycling
      ergometer revealed increased in any of the groups. Tests at the cycling ergometer
      revealed increased maximal effort tolerance for all three groups but the increase
      was more marked in patients taking the combination (who from 130 +/- 10 Watt
      increased to 160 +/- 20 Watt). This was confirmed also by the reduced consumption
      of trinitrine capsules which diminished in groups 1 and 2 from an average of
      5/week to 2/week but was completely abolished in group 3. Also ST depression was
      significantly reduced (p less than 0.05) only in this latter group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1387057
TI  - Allergic contact dermatitis from a cream containing Centella asiatica extract.

PMID- 1387056
TI  - Contact allergy to tioconazole.
AB  - In 15 months, we detected allergic patch test reactions to tioconazole in 14
      patients. 9 of the 14 patients were allergic to additional imidazole derivatives
      used as antifungal agents. The positive patch test reactions to tioconazole may
      have been caused either by simultaneous sensitization or more probably by cross
      reactivity between the various commercially used imidazole derivatives with a
      similar chemical structure. The abundant use of tioconazole in concentrated (up
      to 28%) topical formulations in Finland could be the major cause of the apparent
      increase in allergic reactions.

PMID- 1387059
TI  - Allergic contact dermatitis from oestradiol in oestrogen patches.

PMID- 1387058
TI  - Allergic contact dermatitis from tioconazole. A report of 2 cases.

PMID- 1387060
TI  - Thimerosal allergy and its relevance in Singapore.

PMID- 1387062
TI  - Melamine-formaldehyde contact dermatitis in orthopaedic practice.

PMID- 1387061
TI  - Contact dermatitis due to etofenamate.

PMID- 1387063
TI  - Allergic contact dermatitis from Bowdichia nitida (sucupira) wood.

PMID- 1387064
TI  - Contact dermatitis from etofenamate.

PMID- 1387065
TI  - Occupational allergic contact dermatitis from minoxidil.

PMID- 1387066
TI  - Assignment of the human cyclin D3 gene (CCND3) to chromosome 6p----q13.
AB  - The PRAD1/cyclin D1 gene (CCND1), a member of the D-type cyclin gene family, has
      been implicated as a protooncogene in parathyroid, lymphoid, and mammary tumors.
      We cloned and mapped another member of this family, the human cyclin D3 gene
      (CCND3), to chromosome 6p----q13 using human x rodent hybrids. This assignment
      raises the hypothesis that cyclin D3 may be involved in the pathogenesis of human
      neoplasms with abnormalities of chromosome 6.

PMID- 1387067
TI  - The relative effects of maternal and child problems on the quality of attachment:
      a meta-analysis of attachment in clinical samples.
AB  - In this meta-analysis of 34 clinical studies on attachment the hypothesis is
      tested that maternal problems such as mental illness lead to more deviating
      attachment classification distributions than child problems such as deafness. A
      correspondence analysis on 21 North American studies with normal subjects
      produced a baseline against which the clinical samples could be evaluated.
      Separate analyses were carried out on studies containing the traditional A, B, C
      classifications and on studies that also included the recently discovered D or
      A/C category. Results show that groups with a primary identification of maternal
      problems show attachment classification distributions highly divergent from the
      normal distributions, whereas groups with a primary identification of child
      problems show distributions that are similar to the distributions of normal
      samples. The introduction of the D or A/C classifications (about 15% in normal
      samples) reveals an overrepresentation of D or A/C in the child problem groups,
      but the resulting distribution still is much closer to the normal distributions
      compared to the samples with maternal problems. In clinical samples, the mother
      appears to play a more important role than the child in shaping the quality of
      the infant-mother attachment relationship.

PMID- 1387068
TI  - [Laparoscopic side-to-side gastrojejunostomy].
AB  - Development of laparoscopic stapling devices and growing experience with the new
      method made resective and reconstructive operations on the digestive system
      accessible to laparoscopy. After extensively testing the method on pigs, we now
      report on laparoscopic gastro-jejunostomies performed in two patients for gastric
      stenosis due to inoperable carcinoma of the pancreas. The technique is described.
      It requires expensive instruments and a very skilled surgeon. While being a safe
      procedure in the hands of a well-trained surgeon, it presents a high degree of
      difficulty. Therefore, in order to avoid complications, it should not be advised
      for a large scale application before results of a greater number of cases can be
      presented.

PMID- 1387069
TI  - [Effect of highly active atrial natriuretic peptide and changes of superoxide
      dismutase level in pregnancy induced hypertension].
AB  - In this paper, patients with severe pregnancy induced hypertension (PIH) were
      treated with a highly active atrial natriuretic peptide (haANP). The results
      indicated that the effect of haANP in decreasing blood pressure (BP), clearing
      proteinuria and detumescence was marked. Serum hSOD-1 concentrations after haANP
      infusion decreased significantly (P less than 0.01). This may be related to the
      amelioration of the disease. Serum hSOD-1 concentrations in normal pregnancy and
      mild, moderate PIH were higher than in the non-pregnant. Serum hSOD-1
      concentration in severe PIH was highest. These findings suggested the presence of
      a defence mechanism in the body against oxidative damage on tissues. The
      pathogenesis of PIH may be associated with the defence effect of the hSOD-1, and
      defective free radicals. The initial results suggest that ANP may be related to
      hSOD-1 in normal pregnancy as well as in PIH.

PMID- 1387070
TI  - [221 cases of laparoscopic laser therapy].
AB  - Laparoscopic laser therapy, using a Nd:YAG laser and an Olympus laparoscope, was
      performed in 221 cases. 0.5% dicaine spray was used intraperitoneally. The types
      of operations performed were tubal sterilization in 110 cases, vaporization of
      endometriotic lesions in 76 cases, lysis of pelvic adhesions in 13 cases,
      salpingostomy in 11 cases, salpingostomy for tubal pregnancy in 10 cases, and
      fenestration of cyst of Morgagni in one, the rate of success was 98.2% in
      tubal/sterilization. In 71 cases of endometriosis the pregnancy rate was 32.7%
      for R-AFS stage I-II, and 25.0% for stage III-IV cases. The advantages and
      techniques of the laparoscopic laser therapy were discussed.

PMID- 1387071
TI  - Response to HBV vaccination in patients with severe liver disease. Absence of an
      HLA effect.
AB  - HLA antigen profiles have been used to identify individuals who are likely not to
      respond to HBV vaccination. The majority of these reports have included either
      normal individuals or individuals with severe abnormalities of their immune
      system. The present investigation assessed the rate of HBV vaccination
      seroconversion in 132 individuals with chronic advanced liver disease who were
      referred for possible liver transplantation. Each was vaccinated using a serum
      derived vaccine administered intramuscularly at three consecutive monthly clinic
      visits. As part of their transplant evaluation, each subject also underwent HLA
      typing for class I and class II antigens. Of the 132 subjects vaccinated, only
      47% seroconverted and became HBsAb positive. There was no difference between
      types of liver disease. As expected, individuals older than 55 years of age
      responded less well than those younger than this cutoff age. No difference
      between seroconverters and nonresponders was evident for gender or any individual
      or combination of HLA antigens. In conclusion, individuals with advanced chronic
      liver disease seroconvert less often in response to HBV vaccination than do
      normal individuals. Moreover, unlike normals and the experience with other
      disease groups, no difference in conversion rates was evident for gender.
      Similarly, no difference in seroconversion rates was evident for the two major
      pathophysiologic types of chronic liver disease. Age greater than 55 years was
      associated with a reduced rate of seroconversion.

PMID- 1387072
TI  - Lp(a) in Japanese diabetic children.

PMID- 1387073
TI  - Is combination sulfonylurea and insulin therapy useful in NIDDM patients? A
      metaanalysis.
AB  - OBJECTIVE: To assess the efficacy of combination therapy with insulin and
      sulfonylurea in the treatment of NIDDM. RESEARCH DESIGN AND METHODS: Studies
      published between January 1966 and January 1991 were identified through a
      computerized Medline search and by hand searching the bibliographies of
      identified articles. We identified 17 eligible randomized, controlled trials of
      combination therapy in NIDDM. These trials had a minimum duration of 8 wk and at
      least one of three outcome measures (fasting glucose, HbA1, or C-peptide) with SD
      or SE of the mean reported to do metaanalysis. With standardized forms, three
      independent reviews abstracted measures of study quality and specific descriptive
      information about population, intervention, and outcome measurements. RESULTS: We
      calculated effect size and weighted mean changes of the three outcome measures
      for control and treatment groups. In the treatment group, the fasting plasma
      glucose decreased from a mean of 11.4 mM (206 mg/dl) at baseline to a mean of
      9.16 mM (165 mg/dl) posttreatment, whereas the control group decreased from (11.3
      to 10.8 mM) (204 to 194 mg/dl) (effect size 0.39, P less than 0.0001). For HbA1,
      the treatment group decreased from a baseline of 11.0 to 10.2% compared to 11.0
      and 11.2% in the control group (effect size 0.43, P less than 0.0001). For
      fasting C-peptide, the treatment group increased from 0.49 to 0.58 nM (1.45 to
      1.75 ng/ml) compared with 0.47 and 0.43 (1.42 and 1.30) for the control group
      (effect size 0.26, P less than 0.017). CONCLUSION: Combined insulin-sulfonylurea
      therapy leads to modest improvement in glycemic control compared with insulin
      therapy alone. With combined therapy, lower insulin doses may be used to achieve
      similar control. Obese patients with higher fasting C-peptides may be more likely
      to respond than others.

PMID- 1387074
TI  - Lipoprotein(a) in diabetic patients with and without chronic renal failure.
AB  - OBJECTIVE: To examine the distribution of Lp(a) plasma levels in patients with
      IDDM and NIDDM, and in nondiabetic and IDDM patients with chronic renal failure.
      RESEARCH DESIGN AND METHODS: Cross-sectional study of Lp(a) plasma levels in a
      population of diabetic patients with stable metabolic control, with simultaneous
      determination of plasma lipids, fasting plasma glucose, and HbA1. Thirty-six
      patients with IDDM, 90 with NIDDM, and 41 with chronic renal failure (20 IDDM, 21
      nondiabetic) were compared with 78 control subjects. RESULTS: Lp(a) plasma levels
      were significantly higher in IDDM and NIDDM patients, as well as in nondiabetic
      and IDDM patients with chronic renal failure compared with control subjects. No
      correlation was observed between Lp(a) and lipid plasma levels, fasting plasma
      glucose, and HbA1. CONCLUSIONS: Lp(a) may contribute to the increased prevalence
      of atherosclerotic disease in diabetic patients and patients with chronic renal
      failure, especially in IDDM patients whose lipoprotein pattern was not different
      from that of the control group.

PMID- 1387075
TI  - [Latex proteins as the trigger of respiratory and systemic allergies].
AB  - 56 patients (52 members of the hospital's staff, four with other employment) who
      had hypersensitivity reactions to latex articles and developed an immediate-type
      response to latex extract with the skin-prick test were studied. Specific IgE
      antibodies were present in the enzyme-allergo-sorbent test of 50 of the subjects.
      Latex-containing surgical and household gloves were the main cause of allergies.
      Patients with isolated contact urticaria (n = 8) had a tendency towards lower
      antibody concentrations than those with additional respiratory and/or systemic
      symptoms (n = 48). Occupation-related provocation tests triggered rhinitis in 19,
      conjunctivitis in ten, and bronchial obstruction in six. The main allergen was
      found to be a protein with a relative molecular mass of 58,000, originating from
      the latex milk and passing from the latex glove into the glove powder. In the
      course of usual activities considerable allergen inhalation can occur. Even small
      amounts (e.g. 400 ng/ml) can precipitate significant allergic reactions. The
      results show that the main latex allergen, a glycine-rich protein molecule, can
      cause cutaneous, inhalant and systemic hypersensitivity reactions.

PMID- 1387076
TI  - [Diastolic function of the left ventricle. II. Clinical significance and
      differential therapy of diastolic dysfunction].

PMID- 1387077
TI  - Clinical studies on isradipine in the management of adult hypertensive patients
      at Moi University Teaching Hospital, Eldoret, Kenya.
AB  - In a 16 weeks open label therapeutic trial, studies were performed on isradipine
      (Lomir) to evaluate its haematological and biochemical safety and hypotensive
      capacity in the management of adult black hypertensive patients. The mean sitting
      diastolic blood pressure decreased from 105.5 +/- 9.66 mm hg at the end of the
      washout period to 92.1 +/- 7.59 mm hg at the end of the study, p less than
      0.0001; while the mean standing diastolic blood pressure was 108.0 +/- 7.10 mm hg
      and 93.9 +/- 8.4 mm hg at the end of the washout phase and at the completion of
      the therapy respectively, p less than 0.0001. The corresponding mean sitting
      systolic blood pressures were 155.4 +/- 9.91 mm hg and 140.6 +/- 9.47 mm hg, p
      less than 0.001 while the corresponding mean standing systolic blood pressures
      were 156.6 +/- 12.50 mm hg and 142.6 +/- 9.15 mm hg, p less than 0.001. There
      were negligible changes in the mean heart rate; from 79.5 +/- 9.23 beats per
      minute (bpm) at the end of the placebo phase to 78.2 +/- 9.15 bpm at the end of
      the study in the sitting position, p greater than 0.1. The corresponding mean
      standing values of heart rate were 82.5 +/- 11.33 and 78.6 +/- 8.76, p greater
      than 0.5. The haematological, biochemical and electrocardiographic parameters
      remained within normal limits during the study. Side effects were mild,
      transitory, improved with therapy and consisted of dizziness, palpitations,
      headache, nocturia, tiredness and fainting attacks. The study achieved 96% good
      to-excellent results with respect to both efficacy and tolerability. Isradipine
      (Lomir) is therefore an efficacious and safe antihypertensive agent in the
      management of black adult patients with mild to moderate primary arterial
      hypertension when administered in the dose of upto 2.5 mg twice daily alone or in
      combination with a beta-blocker.

PMID- 1387078
TI  - Acceptable workloads for three common mining materials.
AB  - A series of psychophysical lifting studies was conducted to establish maximum
      acceptable weights of lift (MAWL) for three supply items commonly handled in
      underground coal mines (rock dust bags, ventilation stopping blocks, and crib
      blocks). Each study utilized 12 subjects, all of whom had considerable experience
      working in underground coal mines. Effects of lifting in four postures (standing,
      stooping under a 1.5 m ceiling, stooping under a 1.2 m ceiling, and kneeling)
      were investigated together with four lifting conditions (combinations of lifting
      symmetry and lifting height). The frequency of lifting was set at four per min,
      and the task duration was 15 min. Posture significantly affected the MAWL for the
      rock dust bag (standing MAWL was 7% greater than restricted postures and kneeling
      MAWL was 6.4% less than stopped); however, posture interacted with lifting
      conditions for both of the other materials. Physiological costs were found to be
      significantly greater in the stooped postures compared with kneeling for all
      materials. Other contrasts (standing versus restricted postures, stooping under
      1.5 m ceiling versus stopping under 1.2 m ceiling) did not exhibit significantly
      different levels of energy expenditure. Energy expenditure was significantly
      affected by vertical lifting height; however, the plane of lifting had little
      influence on metabolic cost. Recommended acceptable workloads for the three
      materials are 20.0 kg for the rock dust bag, 16.5 kg for the ventilation stopping
      block, and 14.7 kg for the crib block. These results suggest that miners are
      often required to lift supplies that are substantially heavier than
      psychophysically acceptable lifting limits.

PMID- 1387079
TI  - An ergonomic evaluation of nursing assistants' job in a nursing home.
AB  - Thirty-eight nursing assistants (NAs) in a nursing home ranked and rated 16
      different patient handling tasks for perceived stresses to the low back. The
      nursing assistants were observed for 79 4 h shifts and were videotaped for 14 4 h
      shifts to describe a typical workday and to determine the number of patient
      handling tasks performed per shift, the use of assistive devices, and
      biomechanical stresses to the low back. In addition, data were collected on
      nursing assistants' and patients' characteristics. The top eight ranked tasks
      included transferring patient from toilet to wheelchair (WC), WC to toilet, WC to
      bed, bed to WC, bathtub to WC, chairlift to WC, weighing patients and lifting
      patients up in bed. The mean ratings of perceived exertion for these tasks were
      between 'somewhat hard' and 'hard'. The estimated compressive force on L5/S1 disc
      for the 50th percentile patient weight ranged from 3.7 to 4.9 KN. Nursing
      assistants worked in teams of two and performed 24 patient transfers per 8 h
      shift by manually lifting and carrying patients. Assistive devices (a hydraulic
      lift and gait belt) were used less than 2% of the time. Patient safety and
      comfort, lack of accessibility, physical stresses associated with the devices,
      lack of skill, increased transfer time, and lack of staffing were some of the
      reasons for not using these assistive devices. Environmental barriers (such as
      confined workplaces, an uneven floor surface, lack of adjustability of beds,
      stationary railings around the toilet, etc.) made the job more difficult. Nursing
      assistants had a high prevalence of low-back pain and 51% of nursing assistants
      visited a health care provider in the last three years for work related low-back
      pain.

PMID- 1387080
TI  - Ergonomic research study on aircraft luggage handling.
AB  - In this study, the lifting and carrying of freight and luggage at a large German
      airport is classified by typical conditions of performance. These manual load
      handling tasks take place in height-restricted workplaces. Different methods for
      an ergonomic evaluation of these tasks are used. The results of the
      epidemiological, physiological, and biomechanical studies indicated a strain
      bottleneck during loading tasks in aircraft holds. Therefore, an additional
      laboratory study was done, in order to analyse the influence of work weight and
      weight of work object on heart rate, subjective RPE, and number of work objects
      handled. As a result of the study, the airport has developed a special lifting
      and carrying training for the aircraft handlers which aims to reduce strain on
      the postural and locomotor apparatus by an appropriate technique of work. The
      training programme consists of theoretical instruction by a company doctor and
      practical exercises under the supervision of a specially-trained sports teacher.

PMID- 1387081
TI  - Suppressor analysis suggests a multistep, cyclic mechanism for protein secretion
      in Escherichia coli.
AB  - The sec/prl gene products catalyze the translocation of precursor proteins from
      the cytoplasm of Escherichia coli. Recessive, conditionally lethal mutant alleles
      of these genes (sec mutations) cause a generalized defect in protein secretion;
      dominant suppressor mutant alleles (prl mutations) restore export of precursor
      proteins with altered signal sequences. In prl strains, a precursor protein with
      a defective signal sequence can be selectively targeted to the suppressor gene
      product. When a precursor LacZ hybrid protein is used, the targeted prl protein
      is inactivated by the large, toxic hybrid molecule, a result termed suppressor
      directed inactivation (SDI). Using SDI, two different secretion-related complexes
      can be generated: a pretranslocation complex that contains a hybrid protein with
      an unprocessed signal sequence, and a translocation complex in which the hybrid
      protein is jammed in transmembrane orientation with the signal sequence cleaved.
      Additional Sec proteins that are contained within, and thus sequestered by, each
      of these complexes can be identified when their functional levels are lowered
      using the conditional lethal sec mutations. Results of this genetic analysis
      suggest a multistep pathway for protein secretion in which the translocation
      machinery assembles on demand.

PMID- 1387084
TI  - Inter-study variability in left ventricular mass measurement. Comparison between
      M-mode echography and MRI.
AB  - In order to compare variability in M-mode echography and MRI in the assessment of
      left ventricular mass, 20 echogenic patients without evidence of coronary artery
      disease were investigated. Two MR and two M-echo examinations were performed
      within 4 days by different trained operators, each unaware of the other's
      results. M-mode echo was carried out according to Devereux's method, using the
      'Penn-Cube' formula. MR protocol included multislice (8 to 12) true, short-axis
      spin-echo imaging (10 mm thick with a 1 to 3 mm gap) encompassing the entire left
      ventricle. Planimetry was manually traced with standardized window settings.
      Correlations between both echographic and both MR measurements showed r = 0.89,
      SEE = 22.7 g and r = 0.96, SEE = 11.2 g, respectively. Mean inter-study
      variability was 11 +/- 6.4% and 6.75 +/- 3.8% (P = 0.0021). The threshold value
      corresponding to the 95th percentile of the variability data was 21.5% for
      echography and 13.5% for MR. In conclusion, MR appeared to be a significantly
      more reproducible examination tool, when compared with M-mode echo, for the
      evaluation of left ventricular mass (variability, 63% higher with echo than with
      MR). The main practical consequence of this result lies in the reduced number of
      patients required to demonstrate a significant change in the LVM with MR as
      compared with echography.

PMID- 1387083
TI  - The carboxy-terminal exon of the adenovirus E1A protein is required for E4F
      dependent transcription activation.
AB  - The adenovirus-2 E1A 289R transcription activator protein contains a 49 amino
      acid sequence (designated CR3) that has been suggested to represent the minimal
      domain required for E1A-induced activation of viral early transcription. We show
      here that the non-conserved carboxy-terminal E1A exon contains two
      interchangeable elements that are required for efficient CR3-dependent
      transactivation of the adenovirus E4 promoter in HeLa cells. These two elements
      do not encode independent transactivation functions and have been designated
      auxiliary regions (ARs) 1 and 2. The effects of AR1 and AR2 are not additive,
      suggesting that they contribute a mechanistically analogous function in
      transcription. Previous studies have suggested that two cellular transcription
      factors, ATF-2 and E4F, can function together with E1A to induce transcription of
      the E4 promoter. The importance of respective factors for E4 transcription has
      not been resolved. We find that E1A activation of E4F, but not ATF-2 (or other
      ATF factors), is AR1- and AR2-dependent. This result suggests that E1A induction
      of the E4 promoter in HeLa cells is primarily mediated by E4F.

PMID- 1387082
TI  - Conversion of human interleukin-4 into a high affinity antagonist by a single
      amino acid replacement.
AB  - Interleukin-4 (IL-4) represents a prototypic lymphokine (for a recent review see
      Paul, 1991). It promotes differentiation of B-cells and the proliferation of T-
      and B-cell, and other cell types of the lymphoid system. An antagonist of human
      IL-4 was discovered during the studies presented here after Tyr124 of the
      recombinant protein had been substituted by an aspartic acid residue. This IL-4
      variant, Y124D, bound with high affinity to the IL-4 receptor (KD = 310 pM), but
      retained no detectable proliferative activity for T-cells and inhibited IL-4
      dependent T-cell proliferation competitively (K(i) = 620 pM). The loss of
      efficacy in variant Y124D was estimated to be greater than 100-fold on the basis
      of a weak partial agonist activity for the very sensitive induction of CD23
      positive B-cells. The substitution of Tyr124 by either phenylalanine, histidine,
      asparagine, lysine or glycine resulted in partial agonist variants with unaltered
      receptor binding affinity and relatively small deficiencies in efficacy. These
      results demonstrate that high affinity binding and signal generation can be
      uncoupled efficiently in a ligand of a receptor belonging to the recently
      identified hematopoietin receptor family. In addition we show for the first time,
      that a powerful antagonist acting on the IL-4 receptor system can be derived from
      the IL-4 protein.

PMID- 1387085
TI  - Relative efficacy of angiotensin converting enzyme inhibitors on mortality of
      patients with congestive heart failure: implications of randomized trials and
      role of the aetiology (ischaemic or non-ischaemic) of heart failure.
AB  - We examined the influence of angiotensin converting enzyme inhibitors (ACE
      inhibitors) on mortality in patients with heart failure of both ischaemic or non
      ischaemic origin. Eleven, randomized, placebo-controlled trials of ACE inhibitors
      involving 1266 patients were selected. The follow-up period varied from 3 to 6
      months. Four different ACE inhibitors were used in the 11 clinical trials. A
      total of 679 patients presented with an ischaemic heart failure and 587 with a
      non-ischaemic heart failure. Meta-analysis, performed for both subgroups, showed
      that mortality was significantly decreased in the ischaemic subgroup only
      (ischaemic group: odds ratio 0.45; 95% confidence interval 0.28 to 0.71; non
      ischaemic subgroup: odds ratio 0.7; 95% confidence interval 0.4 to 1.5). Although
      the two odds ratio are not significantly different, further randomized, placebo
      controlled trials with ACE inhibitors are required in order to determine more
      precisely the benefit/risk ratio in patients with non-ischaemic heart failure.

PMID- 1387086
TI  - Distribution of two types of infiltrating helper T cells among rat renal
      allografts, spleen, peripheral blood, and regional lymph node cells.
AB  - Cytokine production by graft-infiltrating cells (GIC) of helper T cell (Th)
      subtypes were investigated in rat kidney allograft compared to those infiltrating
      the spleen, those in peripheral blood, and in regional lymph nodes. The relative
      proportion of OX-22 positive cells (Th type 1) and the W3/25-positive cells (Th)
      of GIC was 49.4 +/- 2.1% on day 3 and 52.7 +/- 2.2% on day 6, whereas those in
      spleen cells was 80.3 +/- 4.1% (p less than 0.05) and 95.5 +/- 2.5% (p less than
      0.01), respectively. GIC produced more B cell-stimulating factor 2 (BSF-2, 106.3
      +/- 8.2 U/ml) when compared to spleen cells (15.9 +/- 4.6 U/ml; p less than
      0.01), peripheral blood mononuclear cells (4.2 +/- 1.0 U/ml; p less than 0.01) or
      lymph node cells (24.9 +/- 4.0 U/ml; p less than 0.01) upon stimulation with
      donor BN lymphocytes in vitro. However, GIC produced less interleukin 2 (IL-2,
      less than 1.0 U/ml) and IL-3 (less than 1.0 U/ml) than produced by spleen cells
      (5.1 +/- 0.9 U/ml, p less than 0.05, and 10.5 +/- 2.3 U/ml, p less than 0.01,
      respectively) or lymph node cells (4.5 +/- 0.4 U/ml, p less than 0.01; 23.5 +/-
      3.1 U/ml, p less than 0.01, respectively). These results demonstrate that the
      subtype of Th cells which produce BSF-2 migrates selectively to allografts.

PMID- 1387087
TI  - Therapeutic lidocaine concentrations have no effect on blood platelet function
      and plasma catecholamine levels.
AB  - The effects of therapeutic plasma concentrations of lidocaine on blood platelet
      function and plasma catecholamine levels were assessed in 9 healthy subjects.
      There were no significant effects on plasma levels of beta-thromboglobulin,
      collagen and adenosine diphosphate-stimulated platelet aggregation, thromboxane
      B2-concentration in plasma after collagen and ADP stimulated platelet
      aggregation, or on plasma nor-adrenaline and adrenaline. No significant
      correlation could be demonstrated between any of the variables tested. Thus, it
      appeared that lidocaine had no effect on platelets that could be of benefit in
      acute myocardial infarction. It should be possible to use lidocaine, in
      combination with thrombolytic therapies without increasing the risk of bleeding
      complications.

PMID- 1387088
TI  - [Age-related non-tumorous lesions in SPF C57BL/6 mice with special reference to
      amyloidosis].
AB  - Non-tumorous pathological changes in C57BL/6 CrSlc mice, which were reared under
      a barrier system and died spontaneously, were examined. At 3 months intervals 125
      to 209 mice were purchased at 4 weeks of age and raised for the supply of aged
      animals. A large portion of the mice were used for various experiments between 3
      and 30 months of age, while not a small number died spontaneously and were
      autopsied. The major non-neoplastic lesion was amyloidosis, with incidence of
      55.5% and 74.4% for the autopsied female and male, respectively. The organs
      involved were the liver, kidneys, spleen, adrenal glands, ileum, heart and lungs.
      Skin ulceration and its scar, cerebral vascular calcification, glomerulosclerosis
      and sepsis in both sexes, distension of the seminal vesicles in males, fibroblast
      growth of the adrenal glands in females were commonly found. Incidence of
      spontaneous neoplastic lesions was 69.7% and 55.1% for the female and male,
      respectively.

PMID- 1387090
TI  - [A trial designed to obtain a specific pathogen free Syrian hamster colony by
      administration of chemicals].
AB  - Conventional Syrian hamsters, contaminated with Giardia spp., Spironucleus muris,
      Trichomonas spp., Pasteurella pneumotropica and Pseudomonas aeruginosa were
      treated with chemicals in order to obtain specific pathogen free animals.
      Hamsters kept in the laminar flow rack were treated orally with metronidazole
      several times to obtain a flagellate-free colony. After all flagellates had been
      eradicated, one pair of animals were kept in an isolator and mating was allowed
      to occur. When their offspring reached the age of seven weeks, they were
      intramuscularly injected daily with netilmicin sulfate for 10 consecutive days.
      Following these treatments, all of the hamsters were free of Pasteurella and
      Pseudomonas. Further breeding of these animals was continued in isolators. To
      confirm the absence of selected pathogens, they were placed in a barrier room for
      further breeding as specific pathogen free animals.

PMID- 1387089
TI  - Fine structure of atrial natriuretic peptide (ANP)-granules in the atrial
      cardiocytes in the hamster, guinea pig, rabbit, cat and dog.
AB  - In the hamster, guinea pig, rabbit, dog and cat, the right and left atria and
      ventricles were examined by immunohistochemistry, and the right auricular
      cardiocytes were studied by transmission electron microscopy. Moreover, ANP
      granules in the cardiocytes were analyzed by ultrastructural morphometry.
      Immunohistochemically, the most intensely ANP-reactive cardiocytes were localized
      in the right auricle, particularly more prominent in the hamster and guinea pig
      than in the rabbit, dog and cat. The immunoreaction in the dog and cat was weaker
      than that in the rabbit. ANP-immunoreactivity was not detected in the ventricular
      myocardium of any of all species examined, but was occasionally observed in the
      subendocardium of the ventricular septum. Ultrastructurally, ANP-granules were
      localized principally in the perinuclear region associated with the Golgi
      apparatus and scattered throughout the sarcoplasmic layers. The Golgi apparatus
      of the cardiocytes was better developed in the hamster and guinea pig than in the
      rabbit, dog and cat. It was poorly-developed in the dog and cat. By
      ultrastructural morphometry, the number of granules was greatest in the hamster
      followed by the guinea pig, rabbit and dog or cat, in this order. On the other
      hand, the diameter of granules was largest in the guinea pig and reduced via the
      hamster to the rabbit. The diameter was significantly smaller in the dog than in
      the rabbit. The diameter of granules of the cat was lay between the rabbit and
      dog.

PMID- 1387091
TI  - Synergistic effects of interleukin 3 and interleukin 11 on murine
      megakaryopoiesis in serum-free culture.
AB  - We investigated the effects of interleukin 11 (IL-11) on murine megakaryopoiesis
      in serum-free cultures, using nonadherent, nonphagocytic, and T-cell-depleted
      bone marrow cells. IL-11 alone had no influence on megakaryocyte (Meg) colony
      formation in serum-free methylcellulose cultures, but it significantly enhanced
      the growth of Meg and granulocyte-macrophage-Meg colonies supported by optimal
      and suboptimal concentrations of interleukin 3 (IL-3). IL-11 also increased the
      size of IL-3-dependent Meg colonies as well as increasing the size and DNA
      content of constituent Meg. In liquid cultures, IL-11 alone did not increase the
      number of Meg, but it enhanced their size and acetylcholinesterase (AchE) levels.
      The addition of IL-11 to cultures containing suboptimal concentrations of IL-3
      resulted in a synergistic increase of Meg AchE. These results suggest that IL-11,
      similarly to interleukin 6, has an effect on Meg and acts synergistically with IL
      3 to augment murine megakaryopoiesis in vitro.

PMID- 1387092
TI  - Dual role of IL-7 in the growth and differentiation of immature thymocytes.
AB  - The effects of interleukin 7 (IL-7) on subpopulations of CD4-CD8- thymocytes from
      young adult mice were tested in vitro. When highly purified CD3-CD4-CD8
      thymocytes were cultured in the presence of recombinant IL-7, significant
      proportions of them became CD4+ and/or CD8+ within a day. CD3+ cells were also
      detected after 2 days. CD3-CD4-CD8- thymocytes were further subdivided into
      interleukin 2 receptor (IL-2R)- and IL-2R+ populations. The majority of the IL-2R
      cells became CD4+ and/or CD8+ in 1 day in the presence of IL-7, and a
      substantial proportion of them also became CD3+ in 2-3 days. No significant
      number of CD4+ or CD8+ cells were generated from the IL-2R+ population under the
      same conditions. However, a small but significant proportion of them became CD3+
      in 3-day cultures with IL-7. Although CD4+/CD8+ cells were also generated from
      the IL-2R- population in 1-day cultures in the absence of IL-7, the viability of
      the cells declined rapidly, and no significant numbers of CD3+ cells were
      generated. In proliferation assays, IL-7 alone vigorously stimulated relatively
      minor subpopulations of CD4-CD8- thymocytes. The IL-7-responsive cells were CD3+,
      did not express the IL-2R or the heat-stable antigen M1/69, and included both T
      cell receptor (TCR)alpha beta + and TCR alpha beta- populations, the latter most
      likely TCR gamma delta +. The CD3+CD4-CD8- thymocytes, stimulated with IL-7 for 3
      days, remained CD4-CD8-. These results demonstrate important roles of IL-7 in the
      growth and differentiation of CD4-CD8- thymocytes in vitro. It functions as a
      survival factor and allows CD3-CD4-CD8- cells to undergo their precommitted
      differentiation without inducing their proliferation, and it also stimulates
      CD3+CD4-CD8-thymocytes to proliferate without inducing their differentiation.

PMID- 1387093
TI  - Lp(a) and the risk of coronary heart disease.
AB  - A screening study was performed on 106 children with familial risk for coronary
      heart disease (CHD) and on matched controls. The two groups differed in several
      parameters. Children of CHD patients exhibited significantly elevated levels of
      Lp(a) and total cholesterol, reduced HDL apo A1 and apo A2 and increased values
      of serum hexuronic acid. These results support the concept that genetic and
      familial factors contribute to the risk of atherosclerosis.

PMID- 1387094
TI  - Lp(a): a link between thrombosis and atherosclerosis.
AB  - Lipoprotein(a), or Lp(a), is a lipoprotein having lipid composition similar to
      that of LDL, but a protein moiety consisting of ApoB 100 linked by disulfide
      bridge to apo(a), a glycoprotein with structural similarity to plasminogen. Lp(a)
      can be both atherogenic and thrombogenic. These two actions are likely to be
      mutually operative, a fact that on a molar basis makes Lp(a) more of a
      cardiovascular pathogen than LDL.

PMID- 1387095
TI  - Fibrinogen/fibrin in atherogenesis.
AB  - Fibrin is a major component of many atherosclerotic plaques. Within the intima
      there is continuous formation of fibrin, and continuous fibrinolysis. In aortic
      lesions, a lipoprotein bound to fibrin can be released by incubation with
      plasmin. Most of this lipoprotein is accounted for by Lp(a). The atherogenicity
      of Lp(a) may be more associated with lipid deposition than with inhibition of
      fibrinolysis. Fibrin degradation products may be chemotactic to monocyte
      macrophages and stimulate smooth muscle cell proliferation.

PMID- 1387097
TI  - Immediate allergy to natural latex: clinical and immunological studies.
AB  - Since 1979 several reports of contact urticaria due to natural latex have been
      documented. In recent years cases of anaphylaxis, rhinitis, and asthma due to
      latex have appeared. Nine patients, studied in our clinic between 1986-1991,
      suffered immediate allergic reactions caused by rubber products. All showed an
      immediate skin reaction to latex extract. Rub testing with surgical gloves was
      positive in eight patients. Immunological techniques (RAST, ELISA, HRT)
      demonstrated specific IgE against latex. Specific bronchial provocation testing
      was performed in one patient who presented with asthma when she used latex
      surgical gloves. Patch testing to common rubber additives were negative in our
      patients. These results suggest that natural latex antigens present in rubber
      objects can cause hypersensitivity reactions probably due to IgE-mediated
      mechanisms.

PMID- 1387096
TI  - Disruption of ovarian development in alligator embryos treated with an aromatase
      inhibitor.
AB  - It has been suggested that sex differentiation in vertebrates is steroid hormone
      dependent, that estrogens play a critical role in ovarian differentiation, and
      that male sex differentiation will occur in the absence of estrogens. Using the
      model of the alligator in which sex can be manipulated by incubation conditions
      (eggs incubated at a constant temperature of 30 degrees produce 100% females, and
      at 33 degrees produce 100% males), a series of experiments using antiestrogens,
      antiandrogen, estradiol-17 beta, dihydrotestosterone (DHT), and aromatase
      inhibitors were performed. Test substances were injected into alligator eggs
      prior to gonadal sex differentiation and the eggs were incubated at male or
      female temperatures until just before expected date of hatching. Gonads were
      excised and the sex was verified histologically. Control embryos injected with
      vehicle produced the expected sex: females at 30 degrees and males at 33 degrees.
      Estradiol in eggs at 33 degrees (male temperature) produced 100% females and did
      not alter female development in eggs at 30 degrees. Antiandrogen, DHT, and a
      steroid antiestrogen had no discernible effect in either the 30 degrees or the 33
      degrees eggs at the doses tested. The aromatase inhibitors aminoglutethimide and
      4-hydroxyandrostenedione caused a moderate disruption of ovarian development and
      had no apparent effect on testicular development. The nonsteroidal aromatase
      inhibitor, Ciba Geigy 16949A, caused inhibition of ovarian development in all
      treated embryos. The Mullerian ducts did not appear to be affected by this
      treatment, or by any of the other treatments, and the gonads did not appear
      masculinized. We conclude that estrogen appears to be necessary for normal
      ovarian development, but that inhibition of estrogen synthesis alone is
      insufficient to cause masculinization. Likewise, exogenous androgens appear
      unable to masculinize embryonic gonads. The evidence suggests that testicular
      differentiation in amniote vertebrates is dependent on factors other than
      androgens or level of estrogens.

PMID- 1387098
TI  - Fetal atrial measurements before and after delivery: correlation with plasma
      atrial natriuretic peptide.
AB  - Fetal and early neonatal atrial measurements correlating with plasma atrial
      natriuretic peptide were studied to evaluate the circulatory change before and
      after delivery in a longitudinal study of 10 normal fetuses from 1 week before
      until 5 days after delivery. Before delivery, right atrial area value was
      significantly larger than that of left atrial area; however, there were no
      significant differences between left and right atrial areas after delivery. Right
      atrial area value before delivery was significantly larger than those after
      delivery, whereas the left atrial area did not change before and after delivery.
      Combined atrial area value before delivery was also larger than those after
      delivery. Plasma atrial natriuretic peptide values did not change after delivery.
      These results suggest that the change from fetal to neonatal circulation mainly
      caused by the pulmonary circulation induces the change of right atrial size
      before and after delivery.

PMID- 1387099
TI  - [The heart in hypertension].

PMID- 1387101
TI  - Abscisic acid and its synthetic analog in relation to growth and nitrogenase
      activity of Azotobacter chroococcum and Nostoc muscorum.
AB  - The plant hormone abscisic acid as well as its synthetic analog LAB 173711
      significantly increased the nitrogenase activity of the bacterium Azotobacter
      chroococcum and the cyanobacterium Nostoc muscorum. The effect depended on the
      concentration of the substances (0.001-10 mg/L) and the age of the cultures. The
      biomass of the organisms was not significantly influenced.

PMID- 1387100
TI  - Role of saccharides in immunoglobulin--Fc receptor interactions.
AB  - The rosettes formed by mouse peritoneal macrophages or DCH-5 cells and TNP
      erythrocytes coated with anti-TNP antibodies of different isotypes were inhibited
      to various extent by monosaccharides. The most effective inhibitors were N
      acetylglucosamine, glucosamine, mannose and N-acetylneuraminic acid in 1-5 mmol/L
      concentrations. Even more efficient were glycopeptides isolated from IgG
      molecules. The Fc receptors (FcRs) released from DCH-5 cells during cultivation
      and gradually separated by affinity chromatography on immobilized IgG reacted
      with aggregated IgG and inhibited the rosette formation. The FcRs eluted by
      monosaccharides influenced mainly the number of rosettes mediated by IgA and IgE
      while those eluted with a glycine-HCl buffer inhibited preferentially IgG
      rosettes. As shown by SDS-PAGE the heterogeneity of the fraction eluted with a
      mixture of monosaccharides revealed one main component with an effective molar
      mass of 50 kg/mol. The glycine-HCl eluate contained two major components of 55
      and 38 kg/mol. The IgG-Sepharose 4B bound all the fractions but only the binding
      of the 50 kg/mol molecule could be inhibited by monosaccharides.

PMID- 1387102
TI  - Prenatal diagnosis of bilirubin-UDP-glucuronosyltransferase deficiency in rats by
      genomic DNA analysis.
AB  - Hepatic bilirubin excretion requires UDP-glucuronosyltransferase-mediated
      glucuronidation. Patients with type I Crigler-Najjar syndrome and mutant rats
      (Gunn strain) inherit deficiency of UDP-glucuronyltransferase activity toward
      bilirubin as an autosomal recessive trait and, as a result, exhibit marked
      nonhemolytic unconjugated hyperbilirubinemia throughout postnatal life.
      Heterozygous carriers of the trait have normal serum bilirubin levels. Because of
      placental excretion of unconjugated bilirubin, type 1 Crigler-Najjar syndrome
      patients and Gunn rats are not jaundiced in utero, making prenatal diagnosis
      difficult. Here we report a diagnostic method in Gunn rats based on genomic DNA
      analysis for prenatal recognition of deficiency of UDP-glucuronyltransferase
      activity toward bilirubin in Gunn rats and identification of heterozygous
      carriers. We and others have shown that two distinct messenger RNA species (UDP
      glucuronyltransferase activity toward bilirubin and the 3-methylcholanthrene
      inducible phenol-UDP-glucuronyltransferase messenger RNA) in Gunn rat liver
      contain identical deletions of a single guanosine residue in their common 3'
      regions. Loss of the restriction site for the endonuclease BstNI, which results
      from this deletion, was used as the basis for a diagnostic test. Female
      heterozygous Gunn rats were mated with male homozygous Gunn rats. Genomic DNA was
      extracted from the chorionic aspect of placenta of 17-day fetuses or from
      leukocytes from normal rats, obligate heterozygotes and homozygous Gunn rats. The
      DNA was sequentially digested with the restriction enzymes EcoRI and BstNI and
      subjected to Southern-blot analysis with a double-stranded DNA probe for the
      common region of UDP-glucuronyltransferase activity toward bilirubin and the 3
      methylcholanthrene-inducible UDP-glucuronyltransferase messenger RNAs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1387103
TI  - Role of the liver in splanchnic extraction of atrial natriuretic factor in the
      rat.
AB  - Mesenteric, hepatic and splanchnic extraction of C-terminal and N-terminal atrial
      natriuretic factor was investigated in male Sprague-Dawley rats. Plasma
      concentrations (mean +/- S.E.M.) of C-terminal atrial natriuretic factor were
      55.0 +/- 6.1 fmol/ml, 31.2 +/- 4.0 fmol/ml and 23.5 +/- 3.3 fmol/ml (n = 12) in
      the abdominal aorta, the portal vein and the hepatic vein, respectively. N
      terminal atrial natriuretic factor plasma levels in these vessels were 3031 +/-
      756 fmol/ml, 2264 +/- 661 fmol/ml and 1618 +/- 496 fmol/ml (n = 6), respectively.
      Although the mesenteric extraction ratio was higher (p less than 0.05) for C
      terminal atrial natriuretic factor (42% +/- 6%) than for N-terminal atrial
      natriuretic factor (28% +/- 4%), there were no significant differences in the
      hepatic extraction ratio (41% +/- 5% vs. 39% +/- 6%) and the splanchnic
      extraction ratio (56% +/- 5% vs. 50% +/- 7%). These data suggest a major role of
      the liver in the splanchnic extraction of C-terminal and of N-terminal atrial
      natriuretic factor in the rat.

PMID- 1387104
TI  - Cholecystolithiasis: lithotherapy for the 1990s.

PMID- 1387106
TI  - Radiation hybrid map spanning the Huntington disease gene region of chromosome 4.
AB  - Radiation hybrid (RH) mapping was used to construct a map of 11 markers in the
      distal 4 Mb of the short arm of chromosome 4, the region containing the
      Huntington disease gene. Two different methods for deriving the order of the
      markers were compared and both arrived at the same order as being the most
      likely. This order is also consistent with both the physical map constructed
      using pulsed-field gel electrophoresis (PFGE) and the meiotic linkage map.
      Comparing the RH map to the map determined by PFGE provided the means to equate
      RH map units (centirays) with actual physical distance in kilobases of DNA. In
      addition, a simple procedure for reducing the complexity of human DNA in
      radiation hybrids is described. One cell line isolated using this procedure
      contains, as its only human DNA, approximately 2 Mb surrounding the Huntington
      disease gene.

PMID- 1387105
TI  - Expression of murine cyclin B1 mRNAs and genetic mapping of related genomic
      sequences.
AB  - Two cDNAs that encode a protein with 87% identity to human cyclin B1 and that
      differ only in the length of their 3'-untranslated regions have been isolated
      from a 70Z/3B murine pre-B leukemia cell library. Three sizes of RNA transcripts
      were detected in Northern hybridization analyses of a variety of normal tissues
      and transformed cell lines using the cDNA inserts as probes. The expression of
      these RNAs can be modulated in tissue culture cell lines by physiologically
      relevant stimuli, increasing when cells are stimulated to proliferate and
      decreasing when cells are induced to differentiate. Moreover, RNAs from tissues
      that contain few proliferating cells have no detectable hybridizing transcripts.
      The coordinate regulation of these RNAs with other genes that are activated
      during the cell division cycle and the profound similarity of the predicted amino
      acid sequence to those of published cyclin B homologues indicate that these genes
      encode a murine cyclin B1. In Southern hybridization analysis of BALB/cAnPt
      genomic DNA digested with EcoRI, 12 fragments hybridized with the cDNA probes.
      Through Southern blot analyses of DNA from backcross and cogenic mice,
      recombinant inbred strains, and somatic cell hybrids, the genetic loci that
      produce the cyclin B1-related sequences (designated loci Cycb1-rs1 to Cycb1-rs9)
      were mapped on mouse chromosomes 5, 1, 17, 4, 14, 13, 7, X, and 8, respectively.
      Cycb1-rs6 (on chromosome 13) is discussed as the most likely candidate for an
      expressed structural gene locus.

PMID- 1387108
TI  - Chromosomal localization of three human D5 dopamine receptor genes.
AB  - It is currently thought that genetic predisposition to imbalances in dopaminergic
      transmission may underlie several neurological disorders, including
      schizophrenia, manic depression, Tourette syndrome, Parkinson disease, Huntington
      disease, and alcohol abuse. Originally two receptors, D1 and D2, were thought to
      account for all of the pharmacological actions of dopamine. However, through
      homology screening three additional genes, D3, D4, and D5, and two pseudogenes
      closely related to D5 have been characterized. To begin our genomic and
      evolutionary analyses of the human D5 dopamine receptor gene and its two
      pseudogenes, we have mapped each of them to their respective chromosomes. By
      combining in situ hybridization results with sequence analysis of PCR products
      from microdissected chromosomes, somatic cell hybrids, and radiation hybrids, we
      have assigned DRD5 (the locus containing the functional human D5 receptor gene)
      to chromosome 4p16.1, DRD5P1 (the locus containing D5 pseudogene 1) to chromosome
      2p11.1-p11.2, and DRD5P2 (the locus of D5 pseudogene 2) to chromosome 1q21.1.

PMID- 1387107
TI  - An estimate of the number of genes in the Huntington disease gene region and the
      identification of 13 transcripts in the 4p16.3 segment.
AB  - Physical mapping and genetic linkage studies have positioned the Huntington
      disease (HD) gene to a relatively large genomic region in the distal portion of
      the short arm of human chromosome 4 (4p16.3). To estimate the number of genes
      present in this region and to identify candidate disease genes, several clones
      that map to the 4p16.3 segment have been examined for clusters of CpG-rich
      restriction sites and transcribed sequences. Thirteen expressed sequences were
      identified and were shown by pulsed-field gel electrophoresis not to cluster into
      a small segment of the 4p16.3 band. The frequency of transcripts in these clones
      suggests that the putative HD gene region contains about 100 genes.

PMID- 1387109
TI  - The mouse CREB (cAMP responsive element binding protein) gene: structure,
      promoter analysis, and chromosomal localization.
AB  - In this paper we report the isolation and characterization of the mouse CREB
      gene. It is composed of 11 exons and 10 introns and spans a region of 70 kb. BR-A
      and BR-B, the two alpha-helical regions of the proposed basic DNA binding domain
      of CREB, are encoded separately on exons 10 and 11. The mouse CREB gene is
      expressed from a promoter that is situated in a CpG island. The promoter contains
      no TATA or CCAAT box homologies but has a number of putative binding sites for
      the acidic transcriptional activator Sp1 and a 9/11 match with the initiator
      region. Transcriptional start site mapping identified five major start sites
      spread over at least 41 nucleotides. Northern blot analysis indicated that
      expression of the CREB gene is almost ubiquitous with expression at differing
      levels of multiple transcripts. Testis expressed a predominant RNA species of
      approximately 1.6 kb. The CREB gene was found to be single copy in the mouse and
      well conserved through evolution. Finally Creb-1, the CREB locus, was mapped to
      the proximal region of mouse chromosome 1.

PMID- 1387110
TI  - Strategies of anti-cytokine monoclonal antibody development: immunoassay of IL-10
      and IL-5 in clinical samples.

PMID- 1387111
TI  - Effects of prolactin and androgens on enzymes of carbohydrate metabolism in
      prostate of castrated bonnet monkeys Macaca radiata (Geoffroy).
AB  - Effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP),
      dihydrotestosterone (DHT) and the combinations of these androgens with PRL/Br on
      the specific activities of caudal and cranial prostatic cellular enzymes involved
      in carbohydrate metabolism in castrated mature bonnet monkeys have been studied.
      Castration decreased all the enzymes studied such as hexokinase (HK), 6
      phosphofructokinase (6-PFK), glyceraldehyde-3-phosphate dehydrogenase (G-3-PD),
      pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and 6
      phosphogluconate dehydrogenase (6-PGD) in the cranial and caudal prostates. PRL
      elevated the activities of all the enzymes above normal except G-3-PD of cranial
      lobe. In the caudal lobe, PRL brought back the activities of HK, PFK, PK, G-6-PD
      to normal and 6-PGD above normal except G-3-PD. TP/DHT treatment increased all
      the enzymes in both the lobes. PRL given along with TP/DHT further enhanced the
      androgen action with regard to HK, PK, G-6-PD and 6-PGD of cranial and PFK, G-3
      PD, PK, G-6-PD and 6-PGD of caudal lobe. Br treatment did not produce any
      alteration of these enzymes in both the lobes. In the cranial lobe, during
      Br+TP/DHT treatment, the stimulating effects of androgen were unaffected on all
      the enzymes except PK. On the other hand in the caudal, the stimulatory effects
      of androgens were affected and the activities of HK, PFK, PK and 6-PGD were
      significantly decreased. The present results suggest that PRL has a direct as
      well as a synergistic action with androgens on enzymes of EMP and HMP shunt in
      the prostates of monkeys.

PMID- 1387112
TI  - Pulmonary atresia with intact ventricular septum and large right ventricle as a
      cause of neonatal heart failure.

PMID- 1387113
TI  - Thymic hyperplasia masquerading as cardiomegaly: MRI validation.

PMID- 1387114
TI  - Cutaneous adverse reactions following the administration of nonsteroidal
      antiinflammatory drugs and antibiotics: an Italian survey.
AB  - The Italian Group for Epidemiological Research in Dermatology (GISED) collected a
      series of cutaneous adverse reactions following NSAID and/or antibiotics
      administered by topical and/or systemic route. Dermatologists from North and
      Central Italy took part in this survey by filling in 1457 case report forms
      during a four-month observation time in 1988-89. The main purpose of our
      epidemiological study aimed at evaluating a post-marketing surveillance program
      by examining spontaneous reports of cutaneous adverse reactions. This result
      seems to be noteworthy, considering the difficulties encountered in Italy to
      develop such a program.

PMID- 1387115
TI  - Laparoscopic common bile duct exploration.
AB  - Laparoscopic cholecystectomy is now the standard approach to gallbladder disease.
      While laparoscopic cholecystectomy offers many advantages over the conventional
      laparotomy procedure one of its drawbacks is that a synchronous common bile duct
      exploration, for so long a cornerstone of management of choledocholithiasis, is
      not yet widely practised laparoscopically. Endoscopic sphincterotomy or open
      surgery, with their attendant hazards and morbidity, remain the most common
      approaches. A flexible choledochoscope with an operating channel may in future
      facilitate laparoscopic management of choledocholithiasis but as yet this is not
      widely available. We report the removal of a common duct stone by dormia basket
      extraction through the cystic duct at laparoscopic cholecystectomy.

PMID- 1387116
TI  - Doxazosin in the management of hypertensive diabetes--a cautionary note (?).
AB  - Twenty-two patients with diabetes and hypertension were treated with Doxazosin.
      An acceptable fall in blood pressure was found with 1 mg. in 50% of patients and
      2-8 mgs. in 50%. An increase in HDL cholesterol and a fall in LDL cholesterol
      levels which reached statistical significance was observed. A small but
      significant increase in HBA1 levels occurred in the 50% of patients on the higher
      Doxazosin dose.

PMID- 1387117
TI  - Prevalence of disabilities in a national sample of 7-year-old Israeli children.
AB  - The prevalence of chronic conditions and illnesses causing disability in Israeli
      Jewish children aged 7 years born in 1975 was studied on the basis of a national
      sample (n = 7,739). Eighty medical conditions causing disability were defined.
      The study showed a total disability rate of 17.5%, which is higher than that
      reported on a similar national sample of 3 year olds (prevalence of 6.9%). The
      percentage of disabilities among very low birthweight children and those with
      family problems was four times greater than in the total population. Mild
      retardation and undefined learning problems were more prevalent among children of
      mothers with low educational level and among children whose birth order was
      fourth or more. Asthma and spastic bronchitis were more prevalent among children
      whose mothers were of European/American origin (P less than 0.05). Behavior and
      mental disorders, learning problems, speech and language disorders were more
      prevalent among male children. Two-thirds of the children with a diagnosed
      problem also had at least one functional disability. There were relatively more
      children from lower social classes in the special education schools than in the
      national sample. Increased prevalence of disabilities among children of very low
      birthweight, low maternal educational level, high birth order, and those from
      families whose origin is Asian/African and from families with intrafamilial
      problems defines the children at risk for disabilities and placement in special
      education schools.

PMID- 1387119
TI  - But is he genetically diseased?

PMID- 1387118
TI  - The role of complement proteins in the pathogenesis of disease.

PMID- 1387121
TI  - [Quality control in epicutaneous testing--reproducibility in the right-left
      comparison].
AB  - In 121 patients, 26 substances of a standard test battery were applied
      symmetrically on both sides of the upper back. The Finn chamber on Scanpor was
      the test system used, the final reading being taken on day 3 or 4. Of 166 tests,
      131 were positive on both sides. Test substances and patients age had no
      influence. In comparison with the results in the literature, ours show a good
      reproducibility of 78.9%. Doubtful reactions (?+) were difficult to evaluate.
      These reactions deserve future research.

PMID- 1387120
TI  - Where is the sure interpreter?

PMID- 1387123
TI  - [Why is 13-cis-retinoic acid (Roaccutane) contraindicated in contact lens
      patients?].

PMID- 1387122
TI  - [Lichenoid eruptions after gold therapy. Report of two cases].
AB  - Lichenoid eruptions appearing in two women receiving chrysotherapy (Solganal B
      oleosum R) a described. The morphological diagnosis, distribution of skin
      eruptions, histological and immunological features and monoclonal antibodies (Leu
      4, Leu 2A and Leu 3A) against several cell surface markers were studied.
      Individual lesions were not distinguishable from idiopathic lichen planus, with
      some features typical for gold lichenoid eruptions: hyperpigmentation,
      psoriasiform eruptions, and hair loss. Histopathological and immunological
      examination of biopsy specimens with monoclonal antibodies generally confirms
      clinical impressions. The authors suggest similar pathogenetic mechanisms in the
      development of idiopathic lichen planus and of lichenoid eruptions after gold
      therapy.

PMID- 1387124
TI  - The health of mothers and fathers with a child with a disability.
AB  - Iris Cairns examined the different effects on the health of mothers and fathers
      when they have a child with a disability. Both have a higher incidence of
      psychiatric morbidity than parents in the general population, with the mothers'
      health more significantly affected than that of the fathers, her study revealed.

PMID- 1387125
TI  - Quantitative determination of calcium-activated myosin adenosine triphosphatase
      activity in rat skeletal muscle fibres.
AB  - A quantitative histochemical technique was developed for determining the kinetics
      of the calcium-activated myosin ATPase (Ca(2+)-myosin ATPase) reaction in rat
      skeletal muscle fibres. Using this technique, the maximum velocity (Vmax) and the
      apparent Michaelis-Menten rate constant for ATP (K(app)) of the Ca(2+)-myosin
      ATPase reaction were measured in type-identified fibres of the rat medial
      gastrocnemius (MG) muscle. The Vmax and the K(app) of the Ca(2+)-myosin ATPase
      reaction were lowest in type I fibres and highest (i.e., approx. two times
      greater) in type IIb fibres. The K(app) in type IIa fibres was similar to that in
      type I. However, the Vmax was 1.5 times greater in type IIa fibres, compared to
      type I fibres. Evidence is presented to suggest that the type IIb fibre
      population in the MG does not represent a single myosin isozyme. In addition, the
      broad range of Vmax and K(app) values indicates that there is marked
      heterogeneity in the myosin heavy chain and myosin light chain composition of
      myosin isozymes among individual fibres.

PMID- 1387126
TI  - Use of etretinate for treatment of primary keratinization disorders (idiopathic
      seborrhea) in cocker spaniels, west highland white terriers, and basset hounds.
AB  - An open clinical trial was used to evaluate the synthetic retinoid, etretinate,
      for treatment of idiopathic seborrhea in Cocker Spaniels, West Highland White
      Terriers, and Basset Hounds. Clinical and histologic improvement was seen in the
      Cocker Spaniels. Etretinate had no beneficial effect on the skin disease of the
      West Highland White Terriers or the Basset Hounds. Etretinate treatment did not
      alter the type or degree of otitis externa. Clinical side effects were minimal.
      Relevant laboratory abnormalities were not detected.

PMID- 1387127
TI  - In vivo antitumor effects of fluoropyrimidines on colon adenocarcinoma 38 and
      enhancement by leucovorin.
AB  - Antitumor effect and active metabolites of fluoropyrimidines were examined in
      mice with transplantable colon adenocarcinoma 38 (Co 38). 5-Fluoro-2'
      deoxyuridine (FUdR) treatment resulted in a much higher level of free 5-fluoro-2'
      deoxyuridine-5'-monophosphate in the tumor than 5-fluorouracil (5-FU) did, and
      thymidylate synthase was almost completely inhibited after FUdR treatment, but
      FUdR showed weaker antitumor activity than 5-FU did. Moreover, 5-fluorouridine
      (FUR) also hardly inhibited tumor growth. A more marked tumor inhibition was
      obtained when FUdR and FUR were administered together. The antitumor activity of
      5-FU was similar to that of the combination of FUdR and FUR. In combination with
      2,2'-anhydro-5-ethyluridine, a uridine phosphorylase inhibitor, FUdR lost its
      antitumor activity, but that of FUR was somewhat potentiated. On the other hand,
      in combination with leucovorin (LV), 5-FU showed markedly potentiated antitumor
      activity, while the antitumor activity of FUdR or FUR was not potentiated.
      Addition of LV to the combination of FUdR and FUR enhanced the inhibitory effect
      of the drugs. From these results, the combination of FUdR and FUR together with
      LV, and the combination of 5-FU and LV seem to be highly efficacious against Co
      38.

PMID- 1387128
TI  - Fast and slow intrafusal fibre type systems in chicken leg muscle spindles.
AB  - The results of this study indicate that in serial sections incubated with
      monoclonal antibodies against MHC and stained for mATPase, intrafusal fibres in
      chicken leg muscle spindles are separable into slow and fast types. As observed
      here, fast fibres are a homogeneous group; however, it had been shown earlier
      (Maier & Zak, 1990) that based on relative amounts of slow MHC, the slow fibres
      can be further divided into 2 subgroups. These 3 types of intrafusal fibre
      conform to 3 recently demonstrated patterns of motor innervation (Maier, 1991).
      It is suggested that the respective actions of slow and fast intrafusal fibres
      produce different components of the afferent discharge of chicken muscle
      spindles.

PMID- 1387130
TI  - Foscarnet and pancytopenia.

PMID- 1387129
TI  - Myosin heavy chain expression in rabbit masseter muscle during postnatal
      development.
AB  - The expression of isoforms of myosin heavy chain (MHC) during postnatal
      development was studied in the masseter muscle of the rabbit. Evidence is
      presented that in addition to adult fast and slow myosin, the rabbit masseter
      contains neonatal and 'cardiac' alpha-MHC. During postnatal growth myosin
      transitions take place from neonatal and fast (IIA, IIA/IIB--referring to a fibre
      containing both IIA and IIB MHCs) MHC to adult 'cardiac' alpha-MHC and I/alpha
      MHC. Since there is a temporary population of fibres containing IIA/alpha-MHC
      during the first 4 wk of development with a peak in the 3rd to 4th wk, the
      transition from IIA-MHC to alpha-MHC may occur in these IIA/alpha-MHC-containing
      fibres. The appearance of 'cardiac' alpha-MHC coincides with the timing of
      weaning, suggesting that the changes in MHC content, that probably result in a
      transition to a lower speed of contraction, have functional significance related
      to weaning. The finding of neonatal MHC in adult rabbits indicates that the
      masseter develops at a rate and in a way that is distinct from most other
      skeletal muscles. A spatiotemporal variation in expression of myosin isozymes
      within the masseter was observed, with many fibres containing more than one
      myosin type, indicating developmentally regulated spatial differences in
      function.

PMID- 1387131
TI  - Clinical trials of antiviral agents.

PMID- 1387132
TI  - Individual efficacy of clarithromycin (A-56268) and its major human metabolite 14
      hydroxy clarithromycin (A-62671) in experimental pneumococcal pneumonia in the
      mouse.
AB  - In man, clarithromycin (A-56268) is metabolized to a 14-hydroxy derivative (14-OH
      clarithromycin, A-62671); this metabolite is absent in mice. An experimental
      mouse model was used to compare the efficacy of clarithromycin versus 14-OH
      clarithromycin in pneumococcal pneumonia by treatment with either the parent drug
      or its 14-OH metabolite alone. Four groups of 15 mice were infected intra
      tracheally with a virulent strain of Streptococcus pneumoniae serotype 3
      (approximately 10(5) cfu/mouse). Treatment was begun 18 h post infection, with
      clarithromycin or erythromycin 50 mg/kg subcutaneously (sc) bd, 14-OH
      clarithromycin 25 mg/kg sc bd or antibiotic free saline sc bd for 24 or 48 h.
      Survival rates ten days after one day of treatment with clarithromycin, 14-OH
      clarithromycin, erythromycin, or saline were 53%, 60%, 27% and 0% respectively.
      After two days treatment the rates were 100%, 100%, 53% (P less than 0.01) and 0%
      respectively. Thirty-six h after two doses, 14-OH clarithromycin demonstrated
      superior intra-pulmonary killing activity to erythromycin (2.7 +/- 0.4 vs 6.6 +/-
      0.8 log10 cfu/mL lung homogenate) (P less than 0.001) and comparable activity to
      clarithromycin (3.6 +/- 1.3 log10 cfu/mL). These results show that clarithromycin
      (50 mg/kg sc) and 14-OH clarithromycin (25 mg/kg sc) have similar in vivo
      efficacy in a mouse model, in which the 14-OH metabolite is not produced from
      clarithromycin. This suggests that in man, the clinical efficacy of
      clarithromycin is not impaired by metabolism to 14-OH clarithromycin, which
      achieves serum concentrations in man of approximately 1 mg/L after multiple doses
      of clarithromycin 500 mg po.

PMID- 1387133
TI  - TLC G-65 in combination with other agents in the therapy of Mycobacterium avium
      infection in beige mice.
AB  - The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in
      combination with rifapentine, clarithromycin, clofazimine and ethambutol, was
      evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated
      Mycobacterium avium infection. TLC G-65 was found to be more active than
      amikacin. The combination of rifapentine and TLC G-65 was more active than either
      agent alone. The activity of clarithromycin in combination with TLC G-65 was
      similar to that of either agent alone. Clofazimine improved the activity of TLC G
      65 with respect to the spleen, while ethambutol improved the activity with
      respect to the liver. Clofazimine and ethambutol enhanced the activity of TLC G
      65 against bacteria in the lungs. TLC G-65 in combination with rifapentine
      appears to be an attractive regimen for the treatment of infections caused by
      bacteria in the M. avium complex.

PMID- 1387134
TI  - Coagulase-negative staphylococci emerging during teicoplanin therapy and the
      determination of their sensitivity.

PMID- 1387135
TI  - Failure of teicoplanin treatment associated with an increase in MIC during
      therapy of Staphylococcus aureus septicaemia.

PMID- 1387136
TI  - Immunocytochemical localization of annexin V (CaBP33), a Ca(2+)-dependent
      phospholipid- and membrane-binding protein, in the rat nervous system and
      skeletal muscles and in the porcine heart.
AB  - We investigated the ultrastructural localization of annexin V a Ca(2+)-dependent
      phospholipid- and membrane-binding protein in the nervous system, heart, and
      skeletal muscles. The results indicate that in the cerebellum the protein is
      restricted to glial cells, where it is found diffusely in the cytoplasm as well
      as associated with plasma membranes. Bergmann glial cell bodies and processes and
      astrocytes in the cerebellar cortex and oligodendrocytes in the cerebellar white
      matter displayed an intense immune reaction product. In sciatic nerves, the
      protein was exclusively found in Schwann cells with a subcellular localization
      similar to that seen in glial cells in the cerebellum. Pituicytes in the
      neurohypophysis were intensely immunostained, whereas axons were not. In the
      heart, annexin V was restricted to the sarcolemma, transverse tubules, and
      intercalated discs. In skeletal muscles the protein was localized to the
      sarcolemma and transverse tubules. No evidence for the presence of the protein in
      the sarcoplasm or in association with mitochondria, the sarcoplasmic reticulum,
      or contractile elements was obtained. The observation that plasma membranes in
      cells expressing annexin V have the protein associated with them is in agreement
      with previous data on Ca(2+)-dependent binding of the protein to brain and heart
      membranes, and on existence of both EGTA- and Triton X-100-extractable and
      resistant fractions of annexin V in these membranes. The present data support the
      hypothesis that annexin V might be involved in membrane trafficking and suggest a
      role for this protein in the regulation of cytoplasmic activities in glial cells.

PMID- 1387137
TI  - Influence of long-term hypoxia on the energy metabolism of the haemoglobin
      containing bivalve Scapharca inaequivalvis: critical O2 levels for metabolic
      depression.
AB  - The oxygen consumption rate of Scapharca inaequivalvis measured under normoxic
      conditions over 48 h showed a significant daily cycle with lowest values
      occurring shortly after the dark period; all hypoxia exposure experiments were
      carried out during the declining part of the cycle. Animals were exposed to a
      constant level of hypoxia for a 12-h period in a series of 14 experiments, each
      at a different oxygen tension. The oxygen consumption was measured continuously,
      and the extent of accumulation of end-products (succinate and propionate), and
      the inhibitory effect of adenosine triphosphate on phosphofructokinase were
      determined at the end of exposures. All three parameters (oxygen consumption, end
      product accumulation, phosphofructokinase inhibition) showed a remarkable
      correlation with major changes occurring between 2.5 and 1.5 ppm (7 and 4 kPa)
      O2. The oxygen consumption rates showed a drop to 6% of the normoxic rate, but a
      consistent low consumption remained below 2 ppm (5.5 kPa) which partly recovered
      over the 12-h exposure period by about three-fold. Succinate and propionate
      accumulated progressively between 2.5 and 1.5 ppm (7 and 4 kPa); at [O2] less
      than 1.5 ppm (4 kPa) the concentration did not increase further, indicating that
      anaerobic metabolism had reached a maximum. Over the same range,
      phosphofructokinase showed an increased sensitivity for adenosine triphosphate,
      the lower inhibitor concentration at 50% Vmax value pointing to depression of
      glycolytic rate. Despite the activation of anaerobic metabolism and the evident
      depression of aerobic metabolism, simple calculation demonstrates that Scapharca
      inaequivalvis relies mainly on aerobic metabolism even during severe
      hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387139
TI  - Plasma endothelin levels in cirrhotic subjects.
AB  - Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is
      released by the vascular endothelium. Plasma immunoreactive endothelin levels
      were measured in 23 patients with cirrhosis and in 20 healthy subjects.
      Concentrations were significantly lower in patients with non-uraemic cirrhosis
      than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less
      than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine
      vasopressin and catecholamines did not show significant correlations with plasma
      endothelin-1 levels. Furthermore, there were no significant differences in plasma
      endothelin levels for etiology of cirrhosis, presence of ascites or varices.
      These data suggest that low circulating endothelin may be involved in the
      development or maintenance of systemic vasodilatation in cirrhosis.

PMID- 1387138
TI  - Influence of aldehydes on selected mechanical properties of resin composites.
AB  - The present study investigated whether propanol, a monofunctional aldehyde, was
      able to improve the mechanical properties of dental polymers. The underlying
      hypothesis was that a cross-linking reaction is possible between various
      functional groups of different polymers. Propanol was added to monomer mixtures,
      which were then made light-curing and loaded with filler. The monomer mixtures
      were varied with respect to monomer composition and content of aldehyde. Four
      mechanical properties of the experimental resin composites were determined.
      Addition of propanol gave rise to significant improvements in mechanical
      properties, which may be indicative of a cross-linking ability of monofunctional
      aldehydes. With the exception of modulus of elasticity, the mechanical properties
      of resin composites based on UEDMA/HEMA were superior to those of BISGMA/TEGDMA
      based materials, even though the improvements in flexural strength and modulus of
      resilience were most pronounced for the BISGMA/TEGDMA-based resin composites.

PMID- 1387140
TI  - Ontogeny and distribution of the murine B cell Fc gamma RII.
AB  - The distribution and expression of the IgG FcRII (Fc gamma RII) on normal murine
      B cells was examined. Using multicolor flow cytometry, spleens from neonatal mice
      of increasing age and adult bone marrow were analyzed for expression of the Fc
      gamma RII. In addition, B cells from peripheral lymphoid organs, as well as panel
      of B cell tumors, were tested. The results demonstrate that the Fc gamma RII is
      expressed on all pre-B cells and immature B cells in the neonatal spleen and
      adult bone marrow, on all mature B cells in peripheral lymphoid organs, and on
      switched B cells in Peyer's patches. Furthermore, the Fc gamma RII was found to
      be present on B cell tumors representative of all stages of B cell maturation and
      differentiation. Taken together, the results indicate that Fc gamma RII is
      expressed during the entire lifetime of the B cell. In addition, examination of
      spleen cells from neonatal mice revealed a large number of pre-B cells,
      phenotypically defined as B220+, IgM-. These pre-B cells were present at birth,
      peaked in number between 2 and 3 wk of age, and became a minor population by day
      30. Further phenotypic analysis of these cells demonstrated the expression of the
      BLA-1 and BP-1 Ag, and the lack of T cell and NK cell markers, thus confirming
      their assignment to the B cell lineage. Finally, the Fc gamma RII present on
      these pre-B cells was shown to be functional, by virtue of its ability to bind
      aggregated IgG.

PMID- 1387141
TI  - Analysis of an in vitro-generated signal that induces systemic immune deviation
      similar to that elicited by antigen injected into the anterior chamber of the
      eye.
AB  - The selective deficit in delayed hypersensitivity that characterizes anterior
      chamber-associated immune deviation (ACAID) is the direct result of a blood
      borne, Ag-specific, cell-associated signal that is created after Ag is injected
      into the anterior chamber of the eye of normal mice. The cells that carry this
      signal via the blood to the spleen express the mature macrophage marker F4/80 and
      are similar to, or perhaps even arise from, F4/80+ dendritic cells found within
      the stroma of normal iris and ciliary body. We have recently reported that ACAID
      inducing properties can be conferred upon conventional F4/80-bearing macrophages
      harvested from the normal peritoneal cavity by incubating these cells in vitro
      with the soluble protein Ag, BSA, in the presence of supernatants harvested from
      cultured iris and ciliary body cells. Using this in vitro induction system, we
      have examined the limiting conditions for conferring ACAID-inducing potential on
      peritoneal exudate cells. We have found that an ACAID-inducing signal can be
      created in vitro with several different soluble Ag, including the retinal
      autoantigen-interphotoreceptor retinol binding protein, and that active
      endocytosis and processing by peritoneal exudate cells is required because
      chloroquine prevents these cells from acquiring ACAID-inducing properties. In
      addition, we have determined that for supernatant-treated peritoneal macrophages
      to induce ACAID to soluble Ag the cells must be 1) alive, 2) injected i.v. or
      i.p. (but not s.c.), and 3) administered to recipients with an anatomically
      intact spleen. When these conditions are met, as few as 20 F4/80+ macrophages
      pulsed with Ag in the presence of iris and ciliary body supernatants are
      sufficient to induce ACAID. Macrophage hybridomas derived from "conventional" APC
      can acquire ACAID-inducing potential in vitro if exposed to iris and ciliary body
      supernatants, whereas macrophage hybridomas derived from "suppressor inducer" APC
      constitutively possess ACAID-induced potential. Peritoneal macrophages that were
      endowed with ACAID-inducing properties by in vitro exposure to supernatants were
      found to elicit splenic suppressor cells similar to those found in spleens of
      mice with ACAID. Moreover, the expression of experimental autoimmune uveitis in
      mice immunized with interphotoreceptor retinol binding protein was significantly
      suppressed if the animals were pretreated with peritoneal exudate cells pulsed
      with this Ag in the presence of iris and ciliary body supernatants.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1387142
TI  - Cyclosporine A and peripheral tolerance. Inhibition of veto cell-mediated clonal
      deletion of postthymic precursor cytotoxic T lymphocytes.
AB  - Veto cell-mediated suppression of CTL responses has been proposed as one
      mechanism by which self tolerance is maintained in mature T cell populations. We
      have reported that murine bone marrow cells cultured in the presence of high-dose
      IL-2 (activated bone marrow cells) mediate strong veto suppressor function in
      vitro and in vivo, and that such veto activity is effected through clonal
      deletion of cytotoxic T cell precursors. In our studies, we have determined that
      bone marrow cell populations from athymic NCr-nu mice (H-2d) mediate strong veto
      cell activity without exposure to exogenous IL-2 in vitro. To examine mechanisms
      by which these naturally occurring veto cell populations in BM suppress precursor
      CTL (pCTL) responses, we used as a responding cell population in MLC, spleen
      cells of transgenic mice expressing at high frequency TCR specific for H-2 Ld
      encoded Ag with stimulation by H-2d-expressing cells in culture. Flow cytometric
      analysis was performed by staining the responding MLC cell population with the
      mAb 1B2 specific for the transgene-encoded TCR and determined changes of 1B2+ T
      cells. Such experiments demonstrated that the anti-H-2d cytotoxic response by
      these cell populations was specifically suppressed by NCr-nu (H-2d) bone marrow,
      and that 1B2+ pCTL were in fact specifically deleted from the responding cell
      population by incubation with such naturally occurring veto cell populations
      expressing the appropriate target Ag. In addition, to further understand the
      interactions of pCTL and veto cells and possible contributions by the latter to
      peripheral tolerance, we evaluated the effect of cyclosporine A (CsA) on veto
      cell-mediated suppression of pCTL of the transgenic mice. CsA inhibited veto cell
      mediated suppression of cytotoxic T cell responses, and this inhibition
      correlated with a lack of clonal deletion of pCTL by veto cells in the presence
      of CsA. Furthermore, CsA exerted its effect through pCTL and not through veto
      cells, indicating that pCTL may play an active role in their own deletion by veto
      cells.

PMID- 1387143
TI  - Age-dependent increase of extrathymic T cells in the liver and their appearance
      in the periphery of older mice.
AB  - The liver is a major site of generation of extrathymic T cells with unique
      properties (e.g., expressing intermediate TCR and containing self-reactive
      clones). We investigated herein whether the levels of extrathymic alpha beta T
      cells varied in various organs as a function of age. A systematic examination of
      the number of mononuclear cells in various organs of BALB/c mice revealed that
      the number of hepatic MNC increased with age whereas the number of thymocytes
      decreased. These changes were more striking in mice fed under conventional
      conditions than under specific pathogen-free condition. The age-dependent changes
      in the number of mononuclear cells in the spleen and lymph nodes were minimal.
      Although the total proportion of alpha beta T cells in each organ remained
      constant, the staining patterns of TCR-alpha beta as shown by immunofluorescence
      profiles varied. The most prominent change was that intermediate TCR-alpha beta
      cells, which constituted a small population in the liver of young mice, expanded
      in the liver of older mice. Intermediate TCR cells appeared even in the periphery
      of older mice. These findings were confirmed by the appearance of extrathymic T
      cells with other unique properties, e.g., double-negative CD4-8- phenotype and
      CD44 expression. In athymic nude mice, only intermediate TCR cells were present
      in the liver and periphery. An age-dependent increase of intermediate TCR cells
      was also seen in these mice. Taken together with the result of bromodeoxyuridine
      injection experiment, which showed an intensive in vivo proliferation of cells in
      the hepatic sinusoids, extrathymic T cells may differentiate predominantly in the
      liver and appeared even to the periphery in older mice.

PMID- 1387145
TI  - T cell receptor expression can switch on and off at a posttranslational level.
AB  - The human T acute lymphocytic leukemia cell line, SUP-T13, is a mosaic of
      TCR/CD3+ and TCR/CD3- cells. Individual SUP-T13 cells can spontaneously switch on
      and off surface TCR/CD3 expression. This switching was demonstrated by culturing
      and analysis of single cell clones that were TCR/CD3+ or TCR/CD3-. The rate of
      switching is about 10(-2)/cell per generation in either direction. This is too
      high to be due to a spontaneous mutation event. Furthermore, switched cells can
      revert at similar rates, as demonstrated by repeated cloning and reanalysis. This
      makes it likely that a regulatory change is responsible for switching. In support
      of this, all known TCR/CD3 proteins are found intracellularly in TCR/CD3- cells,
      and they associate with each other as in TCR/CD3+ cells. Furthermore, no
      structural abnormalities of the TCR/CD3 chains can be seen in TCR/CD3- cells
      using two-dimensional electrophoresis. However, in these cells, the chains
      accumulate in great excess intracellularly. This accumulation is specific to the
      TCR/CD3 complex, as other glycoproteins are still expressed normally on the cell
      surface. Thus, there is regulation of TCR expression at a posttranslational
      level. These TCR/CD3- cells may lead to the identification of novel protein(s)
      involved in glycosylating, processing, or transporting the TCR/CD3 complex.
      Potential loss of TCR/CD3 expression may also limit the feasibility of TCR-based
      therapies for T cell leukemias.

PMID- 1387144
TI  - Induction of cytotoxic T lymphocytes in vivo with protein antigen entrapped in
      membranous vehicles.
AB  - Intravenous administration of APC such as splenocytes loaded with a soluble
      protein Ag has been shown to prime for an Ag-specific CTL response. It is thought
      that the APC directly presents loaded Ag in a MHC-restricted manner. However, it
      is demonstrated in this study that allogeneic splenocytes, MHC-free RBC, and even
      synthetic lipid vesicles (liposomes) after loading with OVA can elicit an OVA
      specific and MHC-restricted CTL response. Biodistribution studies of these Ag
      associated vehicles showed that the liver, spleen, and lung were the major organs
      responsible to scavenge these carriers, suggesting that the monocyte-macrophage
      system was involved in the Ag presentation for CTL. Depletion of macrophages by a
      specific macrophage killer, Cl2MDP, containing liposomes, abolished the CTL
      induction by immunization with OVA Ag carried by these vehicles except the
      induction by syngeneic splenocytes. Thus, the syngeneic splenocytes present Ag
      directly to the T cells, but other membranous vehicles carry the Ag to the host
      APC including macrophages, which then present it to the T cells. These results
      indicate that formulation of an Ag in membranous/colloidal vehicles may be a way
      to prime for a CTL response.

PMID- 1387146
TI  - Direct involvement of the CDR3-like domain of CD4 in T helper cell activation.
AB  - The CD4 glycoprotein, a member of the Ig super-family, has long been known to
      play an important role in the immunologic activation of Th cells. The precise
      manner in which CD4 participates in this activation process is not yet
      understood. In an attempt to further define its role in Th cell activation, we
      modeled the D1 domain of the murine CD4 protein (L3T4) based on the
      experimentally determined high resolution structure of the human CD4 protein.
      Because the D1 domain of CD4 strongly resembles the V kappa chain of an antibody,
      we addressed the question of whether the CDR-like regions of CD4 are also
      involved in mediating protein-protein interactions. Consequently, we used the
      modeled L3T4 structure as a template in the design of conformational mimics of
      the CDR3-like region (residues 86-94). Only the analog designed to mimic both the
      sequence and conformation of this region exhibited highly specific inhibition of
      CD4-dependent responses. Because the inhibitory activity could be localized to
      the Th cell itself, it appears that this analog acts by uncoupling a CD4
      association (independent of an APC) critical to generating a proliferative
      response.

PMID- 1387147
TI  - IL 7-induced T cell receptor-gamma gene expression by pre-T cells in murine fetal
      liver cultures.
AB  - IL-7 has previously been shown to stimulate proliferation of immature CD4-CD8-
      thymocytes from fetal and adult mice. We show that IL-7 mRNA levels are much
      higher in the day-14 fetal thymus than in the adult thymus, i.e., when the thymus
      is primarily composed of CD4-CD8- cells. Inasmuch as IL-7 may, therefore, be one
      of the first cytokines to which pre-T cells from the fetal liver are exposed when
      they migrate to the thymus during development, we hypothesized that IL-7 may
      promote differentiation of pre-T cells from the fetal liver. We found that human
      rIL-7 promotes growth of cells obtained from the liver of fetal mice at day 14 of
      gestation. Moreover, we found that IL-7 stimulated expression of mRNA encoding
      TCR-gamma, alpha-, and beta-genes. The size of the transcripts induced by IL-7
      suggests that TCR-gamma was expressed in a rearranged form in response to IL-7,
      whereas TCR-alpha and -beta genes appeared to be expressed from nonrearranged
      loci. Culture of fetal liver cells for 7 days with IL-7 also caused the
      appearance of a population of cells expressing Thy-1 and Pgp-1 Ag, a phenotype
      similar to that seen in the early (day-14) fetal thymus. The Thy-1+ Pgp-1+
      population was enriched in TCR-gamma mRNA, as determined by flow cytometric
      sorting followed by Northern blot analysis. These data support the hypothesis
      that IL-7 can stimulate some of the early events associated with thymocyte
      differentiation in the fetus.

PMID- 1387148
TI  - Pattern of IL-1 receptor gene expression suggests role in noninflammatory
      processes.
AB  - The cytokine IL-1 can be elaborated by most nucleated cell types and exerts its
      pleiotropic effects on a variety of tissues through binding to its cognate
      receptor. Two forms of IL-1R, designated types I and II, have been identified.
      These proteins share limited amino acid identity but both bind IL-1 alpha and IL
      1 beta. A large number of cell types have been shown to possess IL-1R in vitro,
      but few studies have addressed the question of in vivo expression. Using in situ
      hybridization in normal adult BALB/c mice, we have examined the tissue
      distributions of both IL-1R types. The results demonstrate that although lymphoid
      tissues in healthy animals express low or nondetectable levels of receptor
      transcript, nonlymphoid tissues constitutively express readily detectable levels
      of IL-1R mRNA. Thymus and spleen samples were largely negative for both IL-1R
      types I and II, whereas half of the lymph nodes examined expressed IL-1R type I.
      In nonlymphoid tissues, IL-1R type I transcript was detected in the dentate gyrus
      of the brain, endocrine pancreas, cardiac endothelium, epidermis, dermis, hair
      follicle epithelium, uterine serosa, vaginal stroma, vaginal squamous epithelium,
      developing oocytes, and granulosa cells of ruptured follicles. In contrast, the
      IL-1R type II probe hybridized to epidermis, dermis, and vaginal basal
      epithelium. The two types of IL-1R were rarely, if ever, co-expressed by the same
      cell. The distributional segregation of the receptor types and the expression of
      IL-1R in normal nonlymphoid tissues has broad implications for the role of IL-1
      in homeostatic physiology.

PMID- 1387149
TI  - Tumor necrosis factor-alpha and IL-6 up-regulate IFN-gamma receptor gene
      expression in human monocytic THP-1 cells by transcriptional and post
      transcriptional mechanisms.
AB  - IFN-gamma is a potent activator of monocytic cell functions, including the
      stimulation of TNF-alpha and the control of IL-6 synthesis. These cytokines might
      act as autocrine or paracrine factors together with IFN-gamma in inducing
      biologic responses. In this study, we addressed the question of whether or not
      TNF-alpha and IL-6 play a role in modulating of IFN-gamma binding. Expression of
      IFN-gamma surface receptor was measured in the human monocytic THP-1 cells. The
      capacity of these cells to bind IFN-gamma increased with time after treatment
      with each cytokine. The number of IFN-gamma R per cell rose by three- and
      fourfold after 16 h of treatment with TNF-alpha and IL-6, respectively. Scatchard
      analysis of binding data showed that neither TNF-alpha nor IL-6 affected the
      affinity of IFN-gamma for its receptor. The increased surface expression of IFN
      gamma R induced by TNF-alpha and IL-6 correlated with the rise in IFN-gamma mRNA
      receptor levels. TNF-alpha-mediated up-regulation of IFN-gamma R was due to an
      increase in transcriptional activity of the IFN-gamma R gene, as shown by run-on
      experiments. No significant modulation of IFN-gamma R gene transcription was
      observed in nuclei from cells treated with IL-6, whose effect appeared to be
      related to IFN-gamma mRNA receptor stabilization. Taken together, the present
      results provide, to our knowledge, the first evidence for cytokine-mediated up
      regulation of IFN-gamma R in human monocytic cells. This up-regulation by TNF
      alpha and IL-6, which are both produced by monocytes, occurs through different
      mechanisms, and may be of physiologic relevance in host defense.

PMID- 1387150
TI  - Schistosoma mansoni eggs induce antigen-responsive CD44-hi T helper 2 cells and
      IL-4-secreting CD44-lo cells. Potential for T helper 2 subset differentiation is
      evident at the precursor level.
AB  - Schistosoma mansoni eggs are potent inducers of biased Th2-like immune responses.
      Using a model system where mice are immunized with isolated schistosome eggs, we
      demonstrate that CD44 expression, up-regulation of which has been linked to Th
      cell development, is increased on Th2 cells. We also investigate the functional
      properties of CD44-lo Th cells recovered from the overtly Th2 environment
      constituted by lymph nodes draining sites of egg deposition. Production of high
      levels of IL-4, IL-5, and IL-10 by Th cells responding to egg Ag is shown to be
      the property of a subpopulation expressing CD44-hi. This population of Th cells
      cosegregates with a blasting subpopulation expressing more IL-4R (but similar
      amounts of IL-2R) than Th cells from normal mice. These results indicate that
      mature Th2 cells responding to schistosome eggs are CD44-hi and suggest that they
      use IL-4 as a growth factor. In contrast, CD44-lo cells sorted from lymph node
      populations responding to eggs are able to produce small amounts of IL-4 and IL
      2, but no IL-5 or IL-10. This is surprising, because low expression of CD44 is
      considered a characteristic of Th cell naivite and concomitant ability to produce
      only IL-2. Thus, in lymph nodes responding to schistosome eggs, potential for Th2
      subset differentiation is evident within the CD44-lo precursor Th subpopulation.

PMID- 1387151
TI  - Soluble complement receptor type 1 ameliorates the local and remote organ injury
      after intestinal ischemia-reperfusion in the rat.
AB  - We examined the role of C activation in ischemia reperfusion injury by inhibiting
      C activation in a rat model of mesenteric arterial occlusion. In anesthetized
      rats, 60 min of mesenteric arterial occlusion was followed by 3 h of reperfusion.
      PBS alone or containing soluble C receptor 1 (3 or 6 mg) was administered i.v.
      Controls underwent laparotomy without ischemia. Relative serum C activities were
      assessed by hemolytic assay, neutrophil (polymorphonuclear leukocyte)
      sequestration by tissue content of myeloperoxidase (MPO) activity, intestinal
      mucosal injury by histologic grading, lung vascular permeability by the ratio of
      bronchoalveolar lavage to blood concentration of radiolabeled BSA, and
      endothelial cell injury was quantified by measurement of plasma factor VIII
      related Ag. After reperfusion, PBS-treated animals had increased intestinal MPO
      (0.048 +/- 0.007 U/g) compared to sham (0.022 +/- 0.005 U/g (p less than 0.05))
      and intestinal mucosal injury score (2.490 +/- 0.221) compared to sham (0.331 +/-
      0.045 (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min before
      reperfusion reduced intestinal MPO (0.017 +/- 0.003 U/g (p less than 0.05)) and
      mucosal injury (1.733 +/- 0.168 (p less than 0.05)) compared to PBS control. PBS
      treated animals also demonstrated increased lung MPO (0.314 +/- 0.025 U/g vs
      0.085 +/- 0.018 in sham (p less than 0.05)) and increased lung permeability
      (bronchoalveolar lavage/blood cpm 11.32 +/- 1.35 x 10(-3) vs sham 2.22 +/- 0.19 x
      10(-3) (p less than 0.05)). Treatment with 6 mg soluble C receptor 1 15 min
      before reperfusion or at reperfusion reduced the lung permeability
      (bronchoalveolar lavage/blood cpm 3.90 +/- 0.79 x 10(-3) and 5.08 +/- 0.75,
      respectively (both p less than 0.05)) compared to PBS control, but did not reduce
      lung MPO (0.342 +/- 0.031 U/g and 0.246 +/- 0.025), respectively. Treatment with
      sCR1 also reduced the release of factor VIII-related Ag, 5-day mortality, and C
      hemolytic activity. In this model, C is a major mediator of intestinal injury and
      extraintestinal injury.

PMID- 1387152
TI  - Protein tyrosine phosphorylation induced via the IgG receptors Fc gamma Ri and Fc
      gamma RII in the human monocytic cell line THP-1.
AB  - We have investigated the role of protein tyrosine phosphorylation in
      transmembrane signaling via the IgG receptors Fc gamma RI and Fc gamma RII in the
      human monocytic cell line THP-1. Fc gamma RI and Fc gamma RII were selectively
      engaged using the anti-Fc gamma RI mAb 197 (IgG2a) and the anti-Fc gamma RII mAb
      IV.3 (IgG2b). Addition to cells of mAb 197, but not addition of IgG2a mAb of
      irrelevant specificity, resulted in the rapid induction of cytoplasmic protein
      tyrosine phosphorylation as assessed by antiphosphotyrosine immunoblotting. A
      similar pattern of tyrosine phosphorylation was induced by mAb IV.3, but not by
      control IgG2b mAb. The induction of tyrosine phosphorylation by anti-Fc gamma R
      mAb was not dependent on antibody Fc region-FcR interactions, because tyrosine
      phosphorylation was also induced by cross-linked anti-Fc gamma RI F(ab')2
      fragments and by cross-linked anti-Fc gamma RII Fab fragments. To investigate the
      relationship of Fc gamma R-induced tyrosine phosphorylation and activation of
      phospholipase C, which is known to follow Fc gamma R engagement, we assessed the
      effect of the tyrosine kinase inhibitor herbimycin A on Fc gamma R-induced Ca2+
      flux. Herbimycin A strongly inhibited cellular Ca2+ flux induced by mAb 197, but
      did not inhibit Ca2+ flux induced by aluminum fluoride, suggesting that tyrosine
      phosphorylation may be important in regulating Fc gamma R-mediated activation of
      phospholipase C. Consistent with this, mAb 197 induced rapid phosphorylation of
      the gamma-1 isoform of phospholipase C. Finally, herbimycin A strongly inhibited
      the induction of TNF-alpha mRNA accumulation by Fc gamma R cross-linking. These
      results suggest that protein tyrosine phosphorylation may play an important role
      in the activation of phospholipase C and in the induction of monokine gene
      expression that follows engagement of Fc gamma R in human monocytes.

PMID- 1387154
TI  - [Reconstruction for malignant bone tumor defects by a composite graft--cementless
      arthroplasty].
AB  - Five patients with malignant bone tumor were arthroplastied with Dacron fabric
      enveloped prosthesis without using cement after resection of tumor. Usually
      following the wide resection of the primary lesion, the supporting tissues are
      always lost. Dacron fabric is intended to act as a scaffold upon which connective
      tissue can proliferate and form new ligament and supporting soft tissues. Dacron
      fabric is useful for the repair of ligament, muscles, joint capsule, periosteum,
      and other supporting soft tissues without significant complications. The lengths
      of the released supporting tissues are easily adjustable. Biologic fixation of
      the prosthesis to the soft supporting tissues is successful, then the durability
      of the prosthesis prolongs. The Dacron fabric is capable of inducing and
      supporting the ingrowth of vascular connective tissue which becomes stronger
      thereafter. The author believes that this method provides a stable, functional
      and esthetically pleasing reconstruction.

PMID- 1387153
TI  - Variability in T cell receptor V beta gene usage in human peripheral blood
      lymphocytes. Studies of identical twins, siblings, and insulin-dependent diabetes
      mellitus patients.
AB  - Recent studies focused on the diversity and molecular organization of the human
      TCR-beta complex have begun to establish the genetic basis for the potential
      repertoire of V beta specificities in T cells. The scope and variability of the
      actual repertoire derived from this potential repertoire, however, remains to be
      clarified. In this study, V beta usage by human peripheral T cells derived from
      serial samples of the same individual, identical twins, and the members of three
      nuclear families that include four members with insulin-dependent diabetes
      mellitus (IDDM) was assessed by both quantitative polymerase chain reaction and
      Northern blotting with V beta subfamily-specific probes. Samples taken from the
      same individual over a period of 21 months and analyzed in separate experiments
      indicated stability in the peripheral repertoire, whereas the similarity in
      peripheral V beta usage in a pair of identical twins suggested a strong role for
      genetics in shaping the peripheral T cell repertoire. In contrast, V beta usage
      in siblings and in unrelated individuals was observed to differ substantially. In
      particular, peripheral expression of V beta 3 and V beta 20 differed by more than
      sixfold among members of two different families. Segregation analysis of TCR and
      HLA haplotypes in these families suggested that variation in V beta 20 expression
      was TCR haplotype specific. Subsequent nucleotide sequence analysis of the V beta
      20 gene segment in multiple members of these families revealed the presence of a
      null allele for V beta 20 expression. No consistent significant differences in V
      beta usage were observed in IDDM patients relative to their siblings or between
      identical twins discordant for IDDM. These results suggest that the repertoire of
      peripheral T cell specificities present in different individuals in human
      populations varies dramatically because of the effects of multiple factors,
      including TCR germ-line polymorphism.

PMID- 1387155
TI  - Muscular changes in osteoarthritis of the hip and knee.
AB  - Muscular abnormalities in the patients with degenerative osteoarthritis were
      examined histologically and histochemically. Enzyme stainings for DPNH
      tetrazolium reductase and myosin ATP-ase at pH 10.4 and 4.6 were performed on 26
      vastus lateralis biopsies from the patients with osteoarthritis of the knee and
      21 gluteus medius specimens from those with osteoarthritis of the hip. All
      specimens were obtained at surgery. The patients were all female with their ages
      ranging from 40 to 74 years. Control specimens were obtained from 16 fractured
      females with absence of arthritis. Type 2 fiber atrophy and internal derangement
      of fibers were found in both osteoarthritic and control muscles, but were more
      frequently seen in the vastus lateralis of the patients with osteoarthritis of
      the knee. Abnormal mosaic patterns of fiber types, such as fiber type grouping
      and grouped atrophy of type 2 fibers, were frequently found in the vastus
      lateralis of the patients with osteoarthritis of the knee (73.1%), and less
      frequently in that of controls (6.3%). However, abnormal mosaic patterns were not
      found in the gluteus medius obtained from either osteoarthritic patients or
      control subjects. Abnormal changes in mosaic pattern of fiber types in the vastus
      lateralis of osteoarthritis of the knee may suggest associated motor neuron
      dysfunction; the abnormality was not observed in the gluteus medius specimens of
      the patients with osteoarthritis of the hip, for which a different background in
      neurological factors may be involved.

PMID- 1387156
TI  - Comparison of the effect of a proteolytic enzyme dispase and a chelator for the
      preparation of epidermal sheet from nude mice.
AB  - Histochemical studies of epidermal Langerhans cells require well-preserved
      epidermal sheets. We studied the conditions for the preparation of the epidermal
      sheets from the skin of the ear, hind limb and trunk of nude mice. Two types of
      commercial dispase, and ethylenediaminetetraacetic acid (EDTA), were used at
      several concentrations and the effects were compared. Dermo-epidermal separation
      was evaluated by the preservation of ATPase activity of Langerhans cells in the
      epidermal sheet and by the ultrastructure of epidermal cells (Langerhans cells
      and keratinocytes) as well as epidermal-dermal junction. Good separation depended
      on the combination of the concentration of the reagent and site of the skin. The
      concentrations of both dispase and EDTA effective for separation of the epidermis
      in the nude mouse were lower than those in other mouse strains reported.

PMID- 1387157
TI  - A death involving probenecid.
AB  - A death following deliberate ingestion of approximately 75 g of probenecid in a
      36-year-old man is described. Tissue concentrations of probenecid were highest in
      serum (710 mg/L) and liver (550 mg/kg). Probenecid was also detected in vitreous
      and bile. Ethanol was also detected in blood at 0.13 g/100 mL.

PMID- 1387158
TI  - Work-related injuries in Athens County 1982 to 1986. A comparison of emergency
      department and workers' compensation data.
AB  - In 1987, the Panel on Occupational Safety and Health Statistics issued a report
      concluding that the existing national surveillance system for occupation injuries
      might result in substantial underreporting of occupational injuries. In this
      study, we examined two sources of data on occupational injuries, the National
      Electronic Injury Surveillance System (NEISS) and lost-work time claims to the
      Bureau of Workers' Compensation (BWC), available in one community, Athens County,
      Ohio. Based on comparison of the NEISS and BWC data sets, we conclude that
      neither data set alone gives a complete nor an accurate picture of occupational
      injuries in Athens County. The two may provide a more complete representation of
      occupational injuries when examined together. Using the NEISS and BWC data sets
      in combination results in a total number of injuries higher than that predicted
      by national norms.

PMID- 1387159
TI  - Recurrent giant cell lesion of the nasomaxillary region in a child: excision and
      immediate reconstruction with a free rectus abdominis muscle transfer.

PMID- 1387160
TI  - Structural analysis of HPD.

PMID- 1387161
TI  - Young children with disabilities and assistive technology: the nurse's role on
      multidisciplinary technology teams.
AB  - Considerations for the involvement of nurses in the provision of assistive
      technology in education and intervention settings as members of multidisciplinary
      teams are presented. Philosophical considerations when participating in these
      processes are discussed, followed by a delineation of factors important in the
      selection of appropriate technology. Recommendations are discussed that have
      practical implications for nursing professionals.

PMID- 1387162
TI  - Occurrence of mycotoxins in animal feeds.
AB  - A total of 1120 grain samples of oats, wheat, rye, barley, and maize, delivered
      for processing of mixed feeds for animals, were collected during the years 1975
      to 1979 from commercial feed mills located throughout Poland. In addition, 625
      samples of the commercially mixed feeds and protein concentrates were collected
      during 1976. For the mycotoxin survey, 751 laboratory samples were chosen at
      random and analyzed. When applying confirmatory tests neither aflatoxins B1, B2,
      G1, G2 nor sterigmatocystin, zearalenone, or ochratoxin B were found to be
      present in any of the samples of barley, wheat, rye, or oats. Aflatoxins were
      detected in about 4% of the maize samples. The presence of ochratoxin A in the
      range of 2 to 200 micrograms/kg was evident in 9% of the grain samples. The
      commercially mixed feeds were found to be more contaminated with mycotoxins than
      were the grains. The aflatoxins were confirmed in about 13% of the samples of
      mixed feeds. After the preliminary multimycotoxin analysis, out of 42 feed
      samples that could be suspected of containing ochratoxins, 32 failed to prove
      their presence. Similarly, out of 27 suspected feed samples, zearalenone was
      found only in one (0.5%) sample. The lowest percentage of samples contaminated
      with mycotoxins was found in poultry mixed feeds (4%). The highest contamination
      occurred among the samples of swine rations, where 17% of the samples contained
      aflatoxins and 13% ochratoxins. The protein concentrates contained only
      aflatoxins. Out of 31 analyzed samples, aflatoxins were detected in 19 (61%) in
      concentrations ranging from 5 micrograms/kg to 500 micrograms/kg. In one sample,
      aflatoxin concentration (B1 + B2) reached 1140 micrograms/kg. Practical
      implications of the results are discussed in relation to animal and human safety.

PMID- 1387163
TI  - Treating patients in wheelchairs.

PMID- 1387164
TI  - Brainstem 5-hydroxytrytamine1A binding sites are not down-regulated by agonists
      which induce tolerance in the rat: myoclonus and other serotonergic behaviors.
AB  - To study the regulation of 5-HT1A receptors in the brainstem, the region most
      relevant to the serotonin syndrome and to serotonin-responsive human myoclonic
      disorders, we chronically treated rats with various 5-HT1A agonists and labeled 5
      HT1A sites with [3H]8-OH-DPAT. Daily injection for 30 consecutive days of 10
      mg/kg ip 8-OH-DPAT (pre- and post-synaptic 5-HT1A agonist) significantly
      decreased 8-OH-DPAT-evoked flat body posture, forelimb myoclonus, and hypothermia
      compared to chronic vehicle injection. There was no cross tolerance to 8-OH-DPAT
      in rats chronically injected with ipsapirone or buspirone (presynaptic 5-HT1A
      agonists). However, none of the 5HT1A agonists significantly altered Bmax of
      brainstem 5-HT1A binding sites. Chronic injection with other drugs such as 1
      propranolol, (+/-) pindolol and spiperone (5-HT1A and 5-HT2 antagonists),
      methysergide (5-HT1 and 5-HT2 antagonist), and agonists and antagonists at
      various other 5-HT receptors also had no effect on binding parameters. These data
      demonstrate lack of cross-tolerance between pre- and post-synaptically acting 5
      HT1A agonists and absence of down-regulation of presynaptic 5-HT1A sites at doses
      which induced tolerance of 5-HT1A-mediated behaviors of the serotonin syndrome.
      They suggest changes in the post-synaptic cell rather than the receptor
      recognition site as the mechanism of tolerance.

PMID- 1387165
TI  - A low affinity vasopressin V2-receptor in inherited nephrogenic diabetes
      insipidus.
AB  - Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder
      characterized by renal resistance to the antidiuretic hormonal action of
      vasopressin. This study describes the molecular basis of nephrogenic diabetes
      insipidus in a dog family. Kidney membranes prepared from NDI-affected male
      huskies were examined for vasopressin binding and response. Compared to membranes
      from unaffected canines, those from the kidney inner medulla of NDI-dogs
      possessed normal V2-receptor numbers, but with 10-fold lower affinity for [Arg8]
      vasopressin (AVP). Adenylate cyclase stimulation by AVP in contrast to that by
      forskolin or GTP-analogues was similarly reduced in a dose responsive manner. The
      NDI-affected dogs showed antidiuretic responses to very high doses of V2-specific
      agonists, consistent with their possessing V2-receptors of lower affinity.
      Prolonged treatment with V2-agonists, 1-deamino [D-Arg8] VP (dDAVP) and 1-deamino
      [Val4, Sar7] AVP (dVSAVP), rendered the NDI-affected dogs near normal in terms of
      water intake and urine osmolality.

PMID- 1387166
TI  - Delayed implantation. A case report.
AB  - In cycles in which conception takes place, serum human chorionic gonadotropin
      (hCG) becomes detectable between 8 and 12 days after ovulation. A delayed
      appearance of hCG has been reported in a limited number of cases, most of them
      ending in spontaneous abortion. We encountered a case of ectopic pregnancy
      characterized by a delayed appearance of hCG and accompanied by a complete,
      albeit temporary, halt in the steroidogenic activity of the corpus luteum.
      Although the patient was at risk of developing an ectopic pregnancy, the findings
      made an early diagnosis extremely difficult.

PMID- 1387167
TI  - NMDA antagonist activity of (+/-)-(2SR,4RS)-4-(1H-tetrazol-5-ylmethyl)piperidine
      2-carboxylic acid resides with the (-)-2R,4S-isomer.
AB  - The tetrazole-substituted amino acid (+/-)-(2SR,4RS)-4-(1H-tetrazol-5
      ylmethyl)pip eri dine-2-carboxylic acid (LY233053, (+/-)-1) was resolved into its
      constituent enantiomers by treatment of a key intermediate in the synthesis of
      the racemic amino acid, ethyl (+/-)-cis-4-(cyanomethyl)-N-allylpiperidine-2
      carboxylate, with either 2S,3S- or 2R,3R-di-p-toluoyltartaric acid. These
      resolved amines were then converted as for the racemate to the amino acids (-)-1
      and (+)-1. The activity of this potent and selective NMDA antagonist was found to
      reside with the (-)-isomer of 1 (LY235723). X-ray crystallographic analysis of
      the 2S,3S-di-p-toluoyltartaric acid salt of ethyl cis-4-(cyanomethyl)-N
      allylpiperidine-2-carboxylate showed that the resolved amine, and thus (-)-1,
      possessed the 2R,4S absolute stereochemistry. Affinity for the NMDA receptor was
      determined using the specific radioligand [3H]-(2SR,4RS)-4
      (phosphonomethyl)piperidine-2-carboxylic acid ([3H]CGS 19755; IC50 = 67 +/- 6
      nM), and selective NMDA antagonist activity was determined using a cortical slice
      preparation (IC50 versus 40 microM NMDA = 1.9 +/- 0.24 microM). This compound
      also demonstrated potent NMDA antagonist activity in vivo following systemic
      administration through its ability to block NMDA-induced convulsions in neonatal
      rats, NMDA-induced lethality in mice, and NMDA-induced striatal neuronal
      degeneration in rats.

PMID- 1387168
TI  - Dihydropyrimidine calcium channel blockers. 4. Basic 3-substituted-4-aryl-1,4
      dihydropyrimidine-5-carboxylic acid esters. Potent antihypertensive agents.
AB  - We have examined a series of novel dihydropyrimidine calcium channel blockers
      that contain a basic group attached to either C5 or N3 of the heterocyclic ring.
      Structure-activity studies show that a 1-(phenylmethyl)-4-piperidinyl carbamate
      moiety at N3 and sulfur at C2 are optimal for vasorelaxant activity in vitro and
      impart potent and long-acting antihypertensive activity in vivo. One of these
      compounds (11) was identified as a lead, and the individual enantiomers 12a (R)
      and 12b (S) were synthesized. Two key steps of the synthesis were (1) the
      efficient separation of the diastereomeric ureido derivatives 29a/29b and (2) the
      high-yield transformation of 2-methoxy intermediates 30a/30b to the (p
      methoxybenzyl)thio intermediates 31a/31b. Chirality was demonstrated to be a
      significant determinant of biological activity, with the dihydropyridine receptor
      recognizing the enamino ester moiety (12a) but not the carbamate moiety (12b).
      Dihydropyrimidine 12a is equipotent to nifedipine and amlodipine in vitro. In the
      spontaneously hypertensive rat, dihydropyrimidine 12a is both more potent and
      longer acting than nifedipine and compares most favorably with the long-acting
      dihydropyridine derivative amlodipine. Dihydropyrimidine 12a has the potential
      advantage of being a single enantiomer.

PMID- 1387169
TI  - Laparoscopy for the management of appendicitis.

PMID- 1387170
TI  - Stability of coliphage lambda DNA replication initiator, the lambda O protein.
AB  - The initiator of coliphage lambda DNA replication, lambda O protein, may be
      detected among other 35S-labeled phage and bacterial proteins by a method based
      on immunoprecipitation. This method makes it possible to study lambda O
      proteolytic degradation in lambda plasmid-harboring or lambda phage-infected
      cells; it avoids ultraviolet (u.v.)-irradiation of bacteria, used for depression
      of host protein synthesis, prior to lambda phage infection. We confirm the rapid
      decay of lambda O protein (half-time of 80 s), but we demonstrate the existence
      of a stable lambda O fraction. In the standard five minute pulse-chase
      experiments, 20% of synthesized lambda O is stable. The extension of the
      [35S]methionine pulse, possible in lambda plasmid-harboring cells, leads to a
      linear increase of this fraction, as if a part of the synthesized lambda O was
      constantly made resistant to proteolysis. Less than 5% of lambda O protein
      synthesized during one minute is transformed into a stable form. We presume that
      the stable lambda O is identical with lambda O present in the normal replication
      complex and thus protected from proteases. We cannot find any stable lambda O in
      Escherichia coli recA+ cells that were irradiated with u.v. light prior to lambda
      phage infection, but their recA- counterparts behave normally, suggesting that
      recA function interferes in the assembly of a normal replication complex in u.v.
      irradiated bacteria. The stable lambda O found in lambda plasmid-harboring, amino
      acid-starved relA cells is responsible for the lambda O-dependent lambda plasmid
      replication that occurs in this system in the absence of lambda O synthesis. The
      existence of stable lambda O raises doubt concerning its role as the limiting
      initiator protein in the control of replication. Another significance of lambda O
      rapid degradation is proposed.

PMID- 1387173
TI  - Torsion of the normal adnexa in early pregnancy and laparoscopic detorsion.

PMID- 1387171
TI  - Inheritance of the replication complex by one of two daughter copies during
      lambda plasmid replication in Escherichia coli.
AB  - Direct measurement of DNA synthesis confirmed that lambda plasmid replication
      proceeds for several hours in an amino acid-starved relA mutant of Escherichia
      coli, leading to plasmid amplification; this replication is lambda cro
      independent, but requires the function of lambda O initiator in the absence of
      its synthesis. This suggests that after the assembly of the replication complex
      (RC) at ori lambda the lambda O protein remains in this structure and the
      affinity of lambda O to ori lambda is alleviated in the assembled RC allowing its
      movement along the DNA. During amino acid starvation the lambda plasmid DNA
      synthesis per bacterial mass occurs at a constant level, as would be expected if
      the number of functioning RCs remained constant. This favors the idea that under
      these conditions the next replication round operates due to the activity of the
      RC inherited from the preceding round. Density shift experiments reveal indeed
      that, from two daughter plasmid copies synthesized after the onset of amino acid
      starvation only one is able to enter into the next round of replication. We infer
      that this is the plasmid copy that inherits the lambda O-enclosing RC from the
      previous replication round. Moreover, the same results of density shift
      experiments were obtained for plasmids synthesized before the onset of amino acid
      starvation. Therefore, we presume that in lambda plasmid-harboring bacteria
      growing in nutrient medium, every second plasmid circle bears an RC that
      originates from the preceding round of replication. This structure has to be
      assembled de novo only on the daughter plasmid copy that does not inherit the
      parental RC. In the absence of lambda O initiator synthesis in amino acid-starved
      relA cells this process cannot occur, leaving as the only replication pathway
      that driven by the parental RC. Our results are discussed in relation to the
      model of regulation of lambda plasmid replication.

PMID- 1387172
TI  - Isolated systolic hypertension and subclinical cardiovascular disease in the
      elderly. Initial findings from the Cardiovascular Health Study.
AB  - OBJECTIVE: To assess the association between isolated systolic hypertension (ISH)
      and subclinical disease in adults aged 65 years and above. DESIGN: Medicare
      eligibility lists were used to obtain a representative sample of 5201 community
      dwelling elderly persons for the Cardiovascular Health Study, a National Heart,
      Lung, and Blood Institute--sponsored cohort study of risk factors for coronary
      heart disease and stroke. In this cross-sectional analysis of baseline data, we
      excluded 3012 participants who were receiving antihypertensive medications, had
      clinical cardiovascular disease, or had a diastolic blood pressure of at least 90
      mm Hg. MAIN OUTCOME MEASURES: For electrocardiogram: myocardial infarction, left
      ventricular hypertrophy, and left ventricular mass as measures of myocardial
      damage and strain; for echocardiography: left ventricular mass, fractional
      shortening, and Doppler flow velocities as measures of cardiac systolic and
      diastolic function; and for carotid sonography: carotid arterial intima-media
      thickness as a measure of atherosclerosis. RESULTS: Among the 2189 men and women
      in this analysis, 195 (9%) had ISH (systolic blood pressure, greater than or
      equal to 160 mm Hg) and 596 (23%) had borderline ISH (systolic blood pressure,
      140 to 159 mm Hg). Systolic blood pressure was associated with myocardial
      infarction by electrocardiogram (P = .02). Borderline and definite ISH were
      strongly associated with left ventricular mass (P less than .001). While there
      was little association with cardiac systolic function, borderline and definite
      ISH were associated with cardiac diastolic function (P less than .001). Isolated
      systolic hypertension was also strongly associated with increased intima-media
      thickness of the carotid artery (P less than .001). CONCLUSIONS: While cohort
      analyses of future repeated measures will provide a better assessment of risk,
      both borderline and definite ISH were strongly related to a variety of measures
      of subclinical disease in elderly men and women.

PMID- 1387174
TI  - [Detection of minimal residual disease of acute lymphocytic leukemia using TCR
      delta gene reconstitution].

PMID- 1387175
TI  - [Malignant histiocytosis associated with central neurological symptoms and
      cerebrospinal fluid involvement].
AB  - A 53-year-old woman was admitted with fever and general fatigue in December,
      1988. A diagnosis of malignant histiocytosis (MH) was made based on her high
      level of LDH, thrombocytopenia, mild splenomegaly without systemic
      lymphadenopathy. There was also bone marrow infiltration large atypical cells and
      erythro-phagocytosis. VEPA therapy resulted in complete remission. Visual
      disturbance and left lagophthalmos were recognized in March 1990. These signs
      indicated central nervous system (CNS) relapse which disappeared after
      intrathecal methotrexate injection. The same symptoms and signs appeared after
      another, 5 months. Tumor cells were found not only in the central spinal fluid
      but also in bone marrow. CNS and bone marrow recurrence were treated with
      intrathecal methotrexate injection VEPA therapy and cranial irradiation. We
      diagnosed this case as MH, based on the clinical features which did not include
      systemic lymphadenopathy and laboratory findings although TcR-gamma rearrangement
      was observed in bone marrow cells. Only one case of CNS infiltration diagnosed
      when alive has previously been reported in Japan. We report here a very rare case
      in which by medical treatment CNS infiltrations was improved twice.

PMID- 1387176
TI  - Calponin: localization and regulation of smooth muscle actomyosin MgATPase.

PMID- 1387177
TI  - Isolation of Ca-transport ATPase from bovine aorta membrane by
      immunoprecipitation with scallop SR antibody.

PMID- 1387178
TI  - A preliminary study on a novel regulatory protein for smooth muscle caldesmon.

PMID- 1387179
TI  - Effects of cyclopiazonic acid, a novel Ca(2+)-ATPase inhibitor, on contractile
      responses and an outward current in smooth muscle.

PMID- 1387180
TI  - [A case of Paragonimiasis westermani with pleural effusion eight months after
      migrating subcutaneous induration of the abdominal wall].
AB  - Patients with Paragonimiasis westermani show a typical ring form or nodular
      shadow on chest X-ray, cough, sputum, and hemosputum. Recently, case reports of
      Paragonimiasis westermani, accompanied by pneumothorax and pleural effusion, as
      for Paragonimiasis miyazakii, have been increasing. Paragonimus westermani often
      causes an ectopic infection in various organs such as the peritoneal cavity,
      pleural cavity, pericardium, liver, adrenal gland and brain. Cutaneous
      paragonimiasis is considered one of the typical forms of ectopic infection in its
      earlier phase, but a few unexpected cases of cutaneous Paragonimiasis westermani
      have also been reported. A 68-year old man, who had never eaten fresh-water crab
      or raw sliced meat of wild boar, noticed subcutaneous induration of the abdominal
      wall. The induration had been gradually moving upwards and to the right from the
      infraumbilical region for over 20 days, and then disappeared at the right upper
      lateral abdominal wall. Eight months later, he developed severe pain in the right
      lower chest, and a chest X-ray showed right pleural effusion. Laboratory
      examinations revealed eosinophilia (WBC 3940/mm3, eosinophil 9%), elevated ESR,
      and an elevated serum total IgE level (5517 IU/ml). Ouchterlony's double
      diffusion test performed with the patient's serum in agarose showed strong bands
      toward Paragonimus westermani antigen, compared to Paragonimus miyazakii antigen.
      Immunoelectrophoresis with the patient's serum showed specific bands toward
      Paragonimus westermani antigen. This patient was finally diagnosed as having
      Paragonimiasis westermani infection, and he responded to praziquantel
      administration. The clinical course of this patient appears to be rare in cases
      of Paragonimiasis westermani infection. The clinical course of this case
      resembled some cases of Paragonimiasis miyazakii infection.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1387181
TI  - [A case report of laparoscopic adrenalectomy].
AB  - Laparoscopic left adrenalectomy was performed on a 47 years old male patient with
      primary aldosteronism. Subcutaneous steel traction method was utilized in
      addition to intraperitoneal CO2 insufflation method. The combined use of steel
      traction method reduced CO2 insufflation pressure below 12 mmHg and might reduce
      possibility of CO2-related complications. A left adrenal gland was approached by
      a resection of phrenic colic ligament and a traction of a transverse and
      descending colon. Laparoscopic adrenalectomy has distinct advantages over open
      adrenalectomy in terms of avoidance of skin and muscle incision and rib
      resection, and early convalescence. This less invasive method might prevail in
      near future.

PMID- 1387183
TI  - Stigma in schools: becoming "wise".

PMID- 1387182
TI  - [Diseases of the kidneys and urinary tract and possibilities of their active
      detection in miners].
AB  - The examination of 630 miners aged 18-64 working in the mines of the Lugansk
      region revealed urinary and renal diseases in 15.7% of them. They were affected
      with chronic prostatitis (34.3%), urolithiasis (27.2%), chronic pyelonephritis
      (14.2%), 162 miners (33%) out of 490 had urinary shifts (hematuria in 91,
      proteinuria in 52, both hematuria and proteinuria in 19 examinees) when examined
      upon ascending from the mine. 61 miners had urinary syndrome only after working
      shifts. It was unrelated to relevant diseases. The authors point out the
      necessity of active screening of renal and urinary diseases during routine
      medical check-ups in miners.

PMID- 1387184
TI  - [Pathogenetic mechanisms of heart hypertrophy in arterial hypertension].

PMID- 1387185
TI  - [Changed routines for occupational injury compensation affect mostly women].

PMID- 1387186
TI  - Global status of clinical photodynamic therapy: the registration process for a
      new therapy.
AB  - The clinical use of photodynamic therapy (PDT) has been ongoing for over a
      decade. However, attempts to apply for approval of the therapy from boards of
      health for general use began only in 1989. The unique nature of PDT and the
      resultant changes in the normal drug registration process, as well as steps which
      are being taken to approve PDT for the treatment of endobronchial lung cancer,
      superficial bladder cancer and esophageal cancer are described. The current
      clinical status of PDT in these indications is also reviewed.

PMID- 1387188
TI  - [The creation of a laboratory culture of Anopheles martinius Schingarev, 1926].
AB  - A laboratory colony of Anopheles martinius has been first set up in the world.
      The starting colony was a sample of overwintered females collected in the Takhta
      Kupyr district of Karakalpakia. The colony was reproducing in laboratory for 11
      months (not less than 15 generations). The method for its maintenance is similar
      to that for An. sacharovi.

PMID- 1387187
TI  - Effect of 17 beta-oestradiol on lymphocyte subpopulations, delayed cutaneous
      hypersensitivity responses and mixed lymphocyte reactions in post-menopausal
      women.
AB  - High-dose steroids are known to be potent modulators of the immune response. We
      accordingly investigated the effect of therapeutic doses of 17 beta-oestradiol
      (E2) on cellular immune responses in post-menopausal women. Fifteen (15) healthy
      women who had undergone a natural menopause were treated with E2 in the form of
      100 mg estraderm patches applied twice weekly for 3 out of every 4 weeks over a 3
      month period, followed by combined oestrogen and progestogen formulations as long
      term therapy. Blood samples were taken on two occasions prior to treatment and at
      weeks 1, 3, 4, 7, 9, 12 and 24 after commencing therapy. Lymphocyte subsets (CD2,
      CD4, CD8, CD19, HLA-DR and NK) were studied in each blood sample using a
      monoclonal antibody kit and a two-colour fluorescence flow-cytometer. One-way
      mixed lymphocyte reactions (MLRs) were performed using the same stimulator
      throughout. Delayed hypersensitivity skin tests (DHTs) were carried out twice
      before treatment and at weeks 3, 4, 12 and 24 using Multitest 7-antigen kits
      (Institut Merieux). Lymphocyte subsets did not change significantly with
      treatment, but both the MLRs and the DHTs were significantly depressed, maximally
      so by the third week of treatment. We conclude that therapeutic doses of E2
      modulate certain immune responses. The significance of this is discussed in the
      light of the increasing use of long-term oestrogen replacement therapy.

PMID- 1387189
TI  - [The laboratory cultivation of Phlebotomus papatasi. The nature of the reaction
      of the sandflies to unfavorable environmental conditions].
AB  - The breeding of Phlebotomus papatasi in laboratory setting has been studied for 4
      years. It has been found that in addition to the well-known factors such as
      temperature and humidity, sandfly development is affected by the features of
      reservoirs for their breeding, amount of nutrient substrate, duration of a
      diapause and developmental conditions of their parents. Ph. papatasi responds to
      deterioration of dwelling conditions with prolonged period of development,
      increased number of diapausing larvae and decreased number of emerged imagines,
      i.e. with development inhibition of different degree and movable transfer to
      diapause.

PMID- 1387191
TI  - [The effect of socioeconomic and ecological conditions on tick-borne encephalitis
      morbidity in settled regions].
AB  - A relation between the tick-borne encephalitis morbidity, to the cattle-breeding
      methods and specific and quantitative structure of dairy cattle herds in
      developed regions is discussed. This relation is due to the fact that cows and
      goats are Ixodid hosts and donors of the virus. The factors like use of
      ameliorated pastures in cattle-breeding practice and cattle maintenance in the
      stalls deprive ticks of their hosts and donors of virus. It brings to decrease of
      vector density, valence of foci and human morbidity. On this basis, the prognosis
      of human morbidity in Byelorussia is given for the following decade.

PMID- 1387190
TI  - [The level of insecticide resistance in natural populations of houseflies].
AB  - The resistance to chlorophos and some pyrethroids (permethrin, fenvalerate and
      ethofenprox) were determined in house fly imagos from Moscow, some towns of the
      Moscow Province (Dmitrov, Kolomna, Zagorsk and others). Tajikistan, Turkmenia and
      also Czechoslovakia. The tested populations from the USSR were highly resistant
      to chlorophos (more than 100 times) and susceptible or tolerant to pyrethroids.
      Czechoslovak populations were more resistant to pyrethroids.

PMID- 1387192
TI  - [Decreased humoral immunity to the tick-borne encephalitis virus in the
      population of the western Urals].
AB  - A serological survey of the human population in the western Urals in 1966-1968
      and repeated survey in 1988-1989, the decrease in humoral immunity to tick-borne
      encephalitis virus in all age groups of people was established in most of
      landscape subzones of the region. The most expressive decrease of humoral
      immunity was noted in middle-aged people living in the subzone of broad-leaved
      and coniferous forests and forest steppe.

PMID- 1387193
TI  - [Seasonal variability in the insecticide resistance and irritability of Anopheles
      superpictus].
AB  - The resistance and irritability to malathion, fenitrothion, propoxur and DDT (WHO
      insecticide impregnated papers) in Anopheles superpictus from Dangara District
      were determined three times in season. Complete susceptibility to malathion,
      fenitrothion and DDT and low resistance to propoxur probably based on knockdown
      mechanism were noticed. DDT and malathion irritability levels were high, and
      those for fenitrothion and propoxur were lower. During the season irritability to
      malathion and fenitrothion (organophosphorous compounds) was slightly decreasing,
      and in contrast was increasing to propoxur (carbamate). Irritability to DDT
      (organochloride) considerably fell down in August and achieved the initial level
      in September again. None of the tested insecticides can be recommended for
      residual spraying in Dangara District because of high irritability levels in
      mosquitos or danger of its rapid increase after onset of spraying.

PMID- 1387194
TI  - [Immediate allergic reaction to natural latex with special reference to surgical
      gloves].
AB  - There is an increasing incidence of contact urticaria (CU) and systemic reactions
      to rubber products. 34 patients are presented: Most were atopic (22/34) and women
      (29/34). 24 worked in the medical field. 13 patients showed signs of hand
      dermatitis. In 31 patients, rub and/or pricktests with liquid latex in different
      dilutions and with latex gloves led to positive reactions. The allergen(s) appear
      in part to be watersoluble: 23 of 31 patients revealed positive test reactions to
      an aqueous glove extract. In two patients, urticarial test reactions to TMTD,
      Mercapto-Mix, and PPD-mix were considered as possible contributing factor of CU.
      Scratch tests with corn-starch were negative in all patients. 17 of 29 sera
      showed RAST (radioallergosorbent test) class 0 using latex allergen disks. SDS
      PAGE (sodiumdodecylsulfate-polyacrylamide-electrophoresis) determined protein
      bands of less than or equal to 14 kD (not allergen specific) and approximately 28
      kD. The Western Blot detected the 28 kD protein as allergen in the sera of three
      patients. Isoelectric focusing (IEF) proved no protein bands. Immunoprinting
      performed with sera of five patients presented allergen bands in an pH range
      between 3.8 and 4.55. This shows that radiostaining (immunoprint) is more
      sensitive than the Coomassie Blue staining. Although three sera showed RAST class
      0, immunoblotting detected allergen bands. In these cases the immunoblot appears
      to be more sensitive than the RAST. A cross reactivity between latex and banana
      could not be established. Alternative gloves are Neolon (neoprene) or Elastyren
      (styrene-butadiene polymer).

PMID- 1387195
TI  - Structural and functional analysis of two cryptic plasmids from Lactobacillus
      pentosus MD353 and Lactobacillus plantarum ATCC 8014.
AB  - The DNA sequences of a 2.4 kb plasmid (p353-2) from Lactobacillus pentosus MD353
      and a 1.9 kb plasmid (p8014-2) from Lactobacillus plantarum ATCC 8014 show 81.5%
      overall similarity. Both plasmids carry elements (replication protein gene, plus
      origin and minus-origin of replication), which are typical of plasmids that
      replicate via a rolling-circle mechanism of replication (RCR). Direct evidence
      for an RCR mechanism was obtained by showing the accumulation of single-stranded
      plasmid intermediates in the presence of rifampicin. A minus-origin of
      replication was defined for plasmids p353-2 and p8014-2 based on DNA sequence
      analysis and on its ability to convert single-stranded into double-stranded
      plasmid DNA. Plasmids pLPE323, pLPE350 and pLPC37 that are derived from the p353
      2 or p8014-2 replicon are structurally and segregationally stable in L. pentosus
      MD353, L. plantarum ATCC 8014 and in Lactobacillus casei ATCC 393. The presence
      of Escherichia coli or lambda DNA fragments in vectors derived from p353-2 or
      p8014-2 does not affect the structural stability but results in segregational
      instability of the vectors. The instability increases with increasing size of the
      inserted DNA fragment. Since vectors based on these replicons can be efficiently
      propagated in a wide variety of Lactobacillus species, they are highly suitable
      for cloning and expression of foreign DNA in Lactobacillus, provided that
      selective pressure is applied.

PMID- 1387197
TI  - [Nonparasitic hepatic cysts].
AB  - Serous cyst of the liver are a rare pathology which are often diagnosed during
      surgery. The paper reports 12 cases which were diagnosed during laparoscopy and
      discusses the etiopathogenesis of the disease, the latest diagnostic tools and
      the possible use of surgery. In conclusion, the Authors affirm that surgical
      laparoscopy represents an alternative form of treatment in some cases, such as
      polycystic liver.

PMID- 1387196
TI  - Proteolysis of filament proteins in glial and neuronal cells after in vivo
      stimulation of hippocampal NMDA receptors.
AB  - An intrahippocampal injection of N-methyl-D-aspartate induced the appearance of
      degradation products of both the 68 kiloDalton neurofilament protein and the
      glial fibrillary acidic protein, as revealed by immunoblot techniques. The
      degradation of these two filament proteins was maximal at 10 days after the
      lesion. The degradation patterns were similar to those induced with calpains or
      calcium in vitro. There were no degradation effects on the 200 kD neurofilament
      protein as tested with both mono- and polyclonal antibodies. Consequently, the
      neuronal degeneration after excessive activation of NMDA receptors appears to
      involve calcium activation of proteolytic enzymes. The effects on the glial
      proteins are probably secondary to neuronal damage but could be related to
      calcium dependent processes.

PMID- 1387198
TI  - Role of serotonin receptor subtype in seizures kindled from the feline
      hippocampus.
AB  - This study assessed the effects of a serotonin (5-HT)1A agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT), a 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)
      2-aminopropane (DOI) and a 5-HT2 antagonist ketanserin on fully kindled seizures
      from the hippocampus. 8-OH-DPAT produced a marked suppression in hippocampal
      kindled seizures, while producing behavioral signs similar to those seen in the 5
      HT syndrome. Although DOI and ketanserin did not affect kindled focal epileptic
      activity, DOI shortened and ketanserin prolonged the latency to onset of
      generalized convulsions. Our data suggest that 5-HT1A receptors play an
      inhibitory role in the generation of hippocampal seizures, whereas 5-HT2
      receptors may participate in kindled seizure generalization from this region.

PMID- 1387199
TI  - Pregnenolone sulfate augments NMDA receptor mediated increases in intracellular
      Ca2+ in cultured rat hippocampal neurons.
AB  - The ability of the neuroactive steroid pregnenolone sulfate to alter N-methyl-D
      aspartate (NMDA) receptor-mediated elevations in intracellular Ca2+ ([Ca2+]i) was
      studied in cultured fetal rat hippocampal neurons using microspectrofluorimetry
      and the Ca2+ sensitive indicator fura-2. Pregnenolone sulfate (5-250 microM)
      caused a concentration-dependent and reversible potentiation of the rise (up to
      approximately 800%) in [Ca2+]i induced by NMDA. In contrast, the steroid failed
      to alter basal (unstimulated) [Ca2+]i or to modify the rise in [Ca2+]i that
      occurs when hippocampal neurons are depolarized by high K+ in the presence of the
      NMDA receptor antagonist CPP. These data suggest that the previously reported
      excitatory properties of pregnenolone sulfate may be due, in part, to an
      augmentation of the action of glutamic acid at the NMDA receptor.

PMID- 1387200
TI  - Excitatory 5-HT2-mediated effects on rostral ventrolateral medullary neurones in
      rats.
AB  - Iontophoretic application of the 5-HT2 receptor agonist alpha-methyl-5-HT excited
      41 neurones in the rostral ventrolateral medulla, including a population of
      barosensitive cells. At high ejecting currents (greater than 2-3 x threshold) the
      excitation was replaced by an inhibition. The excitatory responses evoked by low
      doses of alpha-methyl-5-HT were reduced during iontophoretic application of
      ketanserin (2-5 nA) in 8/9 cells. alpha-Methyl-5-HT inhibited ongoing activity of
      a further 28 cells. The inhibitions were not blocked by ketanserin (n = 3). We
      suggest that alpha-methyl-5-HT exerts an excitatory 5-HT2-mediated effect on
      neurones in the rostral ventrolateral medulla.

PMID- 1387201
TI  - Treatment of iris melanoma with photodynamic therapy.
AB  - Photodynamic therapy was used to treat four patients with iris melanoma.
      Hematoporphyrin derivative was used as a sensitizing agent. The tumors were
      exposed to a total dose of 1.72 x 10(6) J/cm2 of 630-nanometer laser light. The
      eye of the first patient, enucleated after treatment, histopathologically showed
      significant tumor necrosis. The tumors in the three subsequent patients were
      almost completely ablated, with no evidence of regrowth.

PMID- 1387202
TI  - The yeast homolog of the U1 snRNP protein 70K is encoded by the SNP1 gene.
AB  - The product of the yeast SNP1 gene has high homology to two domains of the
      metazoan U1 snRNP protein 70K, which binds to stem/loop I of the U1 RNA. However,
      the absence of other domains conserved in metazoan 70K and the minimal effect of
      yeast U1 RNA stem/loop I deletion make the assignment of SNP1 as yeast 70K less
      clear. To address this question, we have expressed the SNP1 gene as a fusion
      protein in E. coli and developed a gel shift assay for U1 RNA binding. We show
      here that the product of the yeast SNP1 gene binds directly and specifically to
      the first 47 nucleotides of yeast U1 RNA, which include the stem/loop 1
      structure. We therefore conclude that the SNP1 gene product is the yeast 70K
      homolog. This is the first yeast protein to be identified as a homolog of a
      metazoan snRNP protein.

PMID- 1387203
TI  - Nucleotide sequences of immunoglobulin heavy and light chain V-regions from a
      monoclonal autoantibody specific for a unique set of small nuclear
      ribonucleoprotein complexes.

PMID- 1387204
TI  - Cloning and sequence analysis of the StsI restriction-modification gene: presence
      of homology to FokI restriction-modification enzymes.
AB  - StsI endonuclease (R.StsI), a type IIs restriction endonuclease found in
      Streptococcus sanguis 54, recognizes the same sequence as FokI but cleaves at
      different positions. A DNA fragment that carried the genes for R.StsI and StsI
      methylase (M.StsI) was cloned from the chromosomal DNA of S.sanguis 54, and its
      nucleotide sequence was analyzed. The endonuclease gene was 1,806 bp long,
      corresponding to a protein of 602 amino acid residues (M(r) = 68,388), and the
      methylase gene was 1,959 bp long, corresponding to a protein of 653 amino acid
      residues (M(r) = 76,064). The assignment of the endonuclease gene was confirmed
      by analysis of the N-terminal amino acid sequence. Genes for the two proteins
      were in a tail-to-tail orientation, separated by a 131-nucleotide intercistronic
      region. The predicted amino acid sequences between the StsI system and the FokI
      system showed a 49% identity between the methylases and a 30% identity between
      the endonucleases. The sequence comparison of M.StsI with various methylases
      showed that the N-terminal half of M.StsI matches M.NIaIII, and the C-terminal
      half matches adenine methylases that recognize GATC and GATATC.

PMID- 1387206
TI  - Evidence for a previously undetected CpG methyl-directed restriction system in E.
      coli.

PMID- 1387205
TI  - Requirements for U2 snRNP addition to yeast pre-mRNA.
AB  - The in vitro spliceosome assembly pathway is conserved between yeast and mammals
      as U1 and U2 snRNPs associate with the pre-mRNA prior to U5 and U4/U6 snRNPs. In
      yeast, U1 snRNP-pre-mRNA complexes are the first splicing complexes visualized on
      native gels, and association with U1 snRNP apparently commits pre-mRNA to the
      spliceosome assembly pathway. The current study addresses U2 snRNP addition to
      commitment complexes. We show that commitment complex formation is relatively
      slow and does not require ATP, whereas U2 snRNP adds to the U1 snRNP complexes in
      a reaction that is relatively fast and requires ATP or hydrolyzable ATP analogs.
      In vitro spliceosome assembly was assayed in extracts derived from strains
      containing several U1 sRNA mutations. The results were consistent with a critical
      role for U1 snRNP in early complex formation. A mutation that disrupts the base
      pairing between the 5' end of U1 snRNA and the 5' splice site allows some U2
      snRNP addition to bypass the ATP requirement, suggesting that ATP may be used to
      destabilize certain U1 snRNP:pre-mRNA interactions to allow subsequent U2 snRNP
      addition.

PMID- 1387207
TI  - [Teicoplanin therapy in neonatal and pediatric intensive therapy].
AB  - We administered teicoplanin as specific antibiotic therapy for nosocomial "ICU
      specific" infections with methicillin-resistant Staphylococcus aureus and
      epidermidis (MRSA-MRSE). The above mentioned drug has been given to 20 patients
      (15 newborns and 5 not-newborns) admitted into intensive care unit during the
      years 1988, 1989, 1990 with MRSA-MRSE localized and/or systemic infection,
      affected by severe disease (RDS, pulmonary edema, congenital cardiac disease,
      cystic fibrosis) undergoing invasive procedures which presented high nosocomial
      infective risk (tracheal intubation, mechanical ventilation, venous and arterial
      cannulation, total parenteral nutrition, etc.). Complete recovery from systemic
      or localized infection (sepsis, low respiratory tract infection, high respiratory
      tract infection) occurred in 19 out of 20 patients, with a rate of success of
      95%. Teicoplanin treatment lasted from a minimum of nine days to a maximum of
      thirty days. The dose was 5-6 mg/kg/die in one administration for the first three
      days, then 4 mg/kg/die. The tolerability of teicoplanin has proven satisfactory,
      since we had no major side effects during treatment and follow up.

PMID- 1387208
TI  - [An association between anorectal malformations and Down's syndrome].
AB  - Down's syndrome is the most frequent chromosomal anomaly in humans and sometimes
      is associated with anorectal anomalies. The anorectal malformations include many
      varieties of anatomical anomalies, which are often difficult to evaluate. The
      Authors believe preoperative CT or MRI of the pelvis, together with other
      clinical and radiological examination to be a valid mean in the preoperative
      prognostic evaluation. In this study they analysed the association of anorectal
      malformations and Down's syndrome and the absence of a genito-urinary or perineal
      fistula.

PMID- 1387209
TI  - [Current views on the mechanisms of regulation of smooth muscle contraction].

PMID- 1387210
TI  - Presynaptic glycine-dependent NMDA receptors mediate enhancement of the release
      of [3H]NA from noradrenergic terminals of rat hippocampus.

PMID- 1387211
TI  - Glucocorticoid effect on lipocortin mRNA expression in U-937 cells.

PMID- 1387212
TI  - Interaction of thiokynurenates with the glycine site regulating N-methyl-D
      aspartate (NMDA) receptors in rat cortical membranes.

PMID- 1387213
TI  - Parenteral administration of antimicrobial drugs can affect the intestinal
      microflora of rat.

PMID- 1387214
TI  - [Cancer of the breast at the time of diagnosis. A national CANAM study: analysis
      of 3007 cases].
AB  - Between April 1988 and February 1990, 3,007 cases of female breast cancer were
      recorded among people insured by CANAM*; 118 cancers were bilateral from the
      start and 2,889 were unilateral. At the time of diagnosis the patients' age
      ranged from 24 to 101 years (median: 60 years), and 35.6 percent of the tumours
      were virtually subclinical. Lymph node involvement was clinically absent in 75
      percent of the cases and histologically absent in 57 percent. In women under 50
      the proportion of small TO-T1 tumours was greater than 40 percent, which pleaded
      for detection before the age of 50 years. Conversely, in economically weak
      populations and in women who were followed up for cancerous disease, breast
      cancer was diagnosed at a later stage. In older (retired) women (median age: 74),
      who accounted for 44 percent of the whole population, the proportion of advanced
      tumours was practically doubled (T4: 11 percent versus 6 percent), and the
      probability of metastases at the time of diagnosis had risen from 4.2 to 6.1
      percent. In these patients, clinical examination once a year should contribute to
      an earlier diagnosis.

PMID- 1387216
TI  - [Alveolar hemorrhage after cocaine inhalation].
AB  - Following inhalation of cocaine two young men developed haemoptysis associated
      with dyspnoea. One of these patients had severe clinical symptoms. There was
      blood eosinophilia, and haemosiderin was found in the macrophages that were
      present in the fibroscopic alveolar lavage fluid. X-ray films of the chest showed
      bilateral micronodular opacities. The outcome was favourable after treatment with
      parenteral dexamethasone, oxygen therapy and mask-administered continuous
      positive pressure ventilation. The frequency of cocaine-induced alveolar
      haemorrhage is probably underestimated; the condition must be suspected in
      subjects who inhale cocaine and have haemoptysis, no matter how small.

PMID- 1387215
TI  - [Deep venous thromboses in erysipelas of the leg. A prospective study of 40
      cases].
AB  - The treatment of lover limb erysipelas rests on antibiotic therapy directed
      against streptococci, but the necessity of prescribing a concomitant
      anticoagulant treatment has not yet been established. The incidence of deep vein
      thrombosis in patients with erysipelas of the leg in unknown. In a prospective
      study of 40 patients presenting with this type of skin disease, we looked for
      deep vein thrombosis, using systematically pulsed Doppler vein exploration
      combined with ultrasonography and, if necessary, a second Doppler examination and
      a phlebography. Six cases of deep vein thrombosis were diagnosed. This
      complication was observed in 5 patients at high risk for deep venous thrombosis;
      it had never been foreseen at clinical examination.

PMID- 1387217
TI  - [Diabetic neuropathy. Difficulties of diagnosis and choice of tests].
AB  - None of the classifications of diabetic neuropathy already published is perfect.
      "Experts" now recommend an operational classification based on the quantification
      of signs and neurological deficits, on an electrophysiological investigation and
      on an easy exploration of autonomic neuropathy. Quantitative evaluation of
      symptoms can be performed with questionnaires or scales. Quantitative evaluation
      of deficits can be performed with devices which quantify vibratory and thermic
      sensations; reproducibility of the results is not yet perfect, but it represents
      a clear progress over clinical examination. Investigation of the autonomic
      control of cardiovascular system with standardized tests is the simplest way of
      exploring the vegetative nervous system; these tests have a fair sensitivity and
      an excellent reproducibility. Therapeutic trials, particularly with aldose
      reductase inhibitors or gangliosides, require this wide panel of neurological
      investigations.

PMID- 1387218
TI  - [Kinetics of decreasing glycemia after injection of insulin: index of sensitivity
      to insulin].

PMID- 1387219
TI  - [Laryngeal pseudotumor related to BCGitis].

PMID- 1387220
TI  - [Collagenous colitis with antinuclear antibodies and chronic neutropenia].

PMID- 1387221
TI  - [Granulomatous mastitis with erythema nodosum. A case].

PMID- 1387222
TI  - [Scarcity of HIV-1-HTLVI/II coinfection in Southern France].

PMID- 1387223
TI  - [Reaction of hypersensitivity to azathioprine].

PMID- 1387224
TI  - [Renal amyloidosis secondary to post-traumatic chronic leg ulcer].

PMID- 1387225
TI  - [Single lung transplantation for idiopathic pulmonary arterial hypertension].

PMID- 1387226
TI  - Protein kinases in dentinogenesis.
AB  - Protein modifications such as phosphorylation and dephosphorylation are known to
      control several cell functions including regulation of the cell cycle, signal
      transduction and enzyme activation/inactivation. Bone and dentin contain highly
      phosphorylated anionic proteins that appear to be involved in the regulation of
      mineralization. This study was designed to identify and characterize the
      enzyme(s) responsible for phosphorylation (kinases) of dentin phosphoprotein
      (DPP) during dentinogenesis. DPP-protein kinase activity was demonstrated in a
      crude homogenate of dental pulp and odontoblast cells. In parallel studies,
      oligonucleotides to conserved amino acid sequences present in the active site of
      kinases were constructed and used to screen a lambda-gt11 tooth organ cDNA
      library. Several cDNA clones were isolated, the size of the insert determined by
      PCR (polymerase chain reaction) amplification, and in situ hybridization was used
      to determine cellular localization during tooth organ development. Preliminary
      evidence provides additional molecular determinants involved with candidate
      kinases responsible for DPP phosphorylation and dentinogenesis.

PMID- 1387227
TI  - Morphological characterization of hypersensitive human radicular dentin and the
      effect of a light-curing resin liner on tubular occlusion.
AB  - A dentin biopsy technique was employed to compare the morphological features of
      hypersensitive and non-sensitive human radicular dentin. Specimens sampled from
      different areas in the same root surface displaying hypersensitivity or non
      sensitivity were prepared for examination in the scanning electron microscope
      (SEM). Before analysis some specimens were exposed to surface demineralization
      and digestion of collagen to allow observation of subsurface portions of the
      dentinal tubules. In another set of observations the potential of a light-curing
      resin liner to penetrate root dentin in vitro and to maintain tubular occlusion
      over time following treatment of hypersensitive radicular dentin were examined.
      Orifices of many dentinal tubules were open in hypersensitive regions while non
      sensitive areas generally displayed tubules occluded with mineralized material.
      SEM-images of HCl-collagenase treated specimens demonstrated the frequent
      presence of membrane-like structures in tubules of hypersensitive dentin. In non
      sensitive dentin these structures were sparse. Topical application of a light
      curing resin liner to wedge shaped defects prepared in radicular dentin of
      extracted human teeth resulted in a surface coating with a resin thickness of 20
      50 microns. Resin penetrated dentinal tubules to a depth of more than 5 microns.
      Dentin biopsies examined 6 months after treatment with the liner showed presence
      of resin-like material in a majority of the tubules in dentin where
      hypersensitivity was no longer perceived. In none of the specimens did the liner
      remain as a surface coating. In areas of recurrent hypersensitivity more than
      half of the tubules presented with open orifices.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1387228
TI  - Effect of a reduction in sodium intake on cold-induced elevation of blood
      pressure in the rat.
AB  - Chronic exposure of rats to cold (5 degrees C) induces hypertension within 3
      weeks. The objective of this study was to determine the effect of treatment with
      graded levels of dietary NaCl on the induction of hypertension during chronic
      exposure to cold. Four groups of male rats were used. The first, given a
      commercial sodium-deficient diet containing 0.30% NaCl, served as the warm
      adapted control group. The second, third, and fourth groups were given the same
      diet containing 0.075%, 0.15%, and 0.30% NaCl, respectively. Because cold-exposed
      rats ingest approximately twice as much food as warm-adapted controls, this
      represented half, the same, and twice the amount of NaCl ingested by the control
      group. The latter three groups were placed in cold air (5 degrees C). All cold
      treated groups had an elevation of systolic blood pressure that was proportional
      to the concentration of NaCl in the diet by the seventeenth week of exposure to
      cold. Cardiac hypertrophy occurred to the same extent in all cold-exposed groups
      and was thus unaffected by the NaCl content of the diet or by the extent of
      elevation of blood pressure. Hence, cardiac hypertrophy during chronic exposure
      to cold is supported by other factors, possibly by the increased concentration of
      either norepinephrine or triiodothyronine, or both, which occurs
      characteristically in rats under these conditions. The results of this experiment
      suggest that the amount of NaCl ingested daily plays a role in the cold-induced
      elevation of blood pressure observed in rats.

PMID- 1387229
TI  - ATP-dependent renal H+ translocation: regional localization, kinetic
      characteristics, and chloride dependence.
AB  - We characterized Mg(2+)-dependent ATPase activity in membranes from the renal
      cortex, the outer and inner stripes of the outer medulla, and papillary vesicles.
      In all regions, there was Mg(2+)-dependent ATPase activity that was resistant to
      oligomycin and vanadate and sensitive to N,N'-dicyclohexylcarbodiimide (DCCD), N
      ethylmaleimide, and filipin. DCCD-Sensitive Mg(2+)-ATPase activity was highest in
      the inner stripe of the outer medulla and lowest in the cortex, with intermediate
      values in the outer stripe of the outer medulla and papilla. The Km for ATP,
      however, was similar among the different regions of the kidney. DCCD-Sensitive
      Mg(2+)-ATPase activity was critically dependent upon chloride with Km for Cl- in
      the range of 2-5 mM. In the presence of ATP, this ATPase was capable of H+
      translocation, as assessed by acridine orange quenching. Inhibitors of ATPase
      activity prevented H+ translocation, which suggests that the Mg(2+)-ATPase
      represents, at least in part, an H(+)-ATPase. H+ transport was likewise
      critically dependent upon chloride, with similar Km. The effect of chloride on H+
      translocation was blocked by the chloride channel inhibitor, diphenylamine-2
      carboxylic acid. In the absence of chloride, H+ transport was abolished, but it
      could be partially restored by the creation of a favorable electric gradient by
      K+ and valinomycin. These studies demonstrate that the renal H(+)-ATPase exhibits
      different activities in various regions of the kidney. The ATPase activity and H+
      translocation are critically dependent upon the presence of chloride, which
      suggests that chloride influences H+ translocation by dissipating the H+ gradient
      and acting at the catalytic site of the ATPase.

PMID- 1387230
TI  - Effects of dietary essential fatty acid deficiency on the development of the rat
      thymus and immune system.
AB  - The paper describes an effect of essential fatty acid (EFA) deficiency on the
      development of the rat thymus and pups' immune system. From birth until being
      weaned (22nd day), the pups were hand-fed artificial milk diets containing a low
      (EFA-D) or high (EFA-R) proportion of EFA in the lipid fraction. The weight
      parameters of the body, thymus and spleen, the fatty acid composition of the
      individual thymus phospholipid subclasses, and mitogen-induced proliferation of
      thymus and spleen lymphocytes were studied. The results show that the total body
      weight of the EFA-deficient (EFA-D) fed animals was significantly decreased in
      comparison with the EFA-rich (EFA-R) and rat milk hand-fed animals. For the EFA-D
      group of young rats a high level of the (n-9) and (n-7) series fatty acids
      [mainly oleic 18:1(n-9) and eicosatrienoic 20:3(n-9) acids] was characteristic of
      the fatty acids in phosphatidylcholine and phosphatidylethanolamine in the
      thymus, compensating for the reduction of the content of arachidonic acid 20:4(n
      6). The biochemical index of the EFA nutritional deficit in the thymus tissue was
      observable as early as on day 7. The mitogen-induced (Con A) proliferation of the
      thymus and spleen lymphocytes was decreased both on the 30th and 40th day of
      life. The results show that the EFA nutritional deficit in the early postnatal
      period caused damage to the structure of thymus in the young rats, most probably
      as a result of the change in the composition of the lipid fraction. These changes
      also affected the development of the immune system of the whole organism.

PMID- 1387231
TI  - Pharmacokinetics of omega-3-fatty acids during ingestion of fish oil
      preparations.
AB  - An in vivo comparison of three dosages (3 g, 6 g, 12 g) of two different fish oil
      preparations in terms of plasma concentrations of their major active components
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was performed. The
      plasma accumulation was measured during 28 days of ingestion and an equally long
      wash out period. Data were scrutinized for bioavailability in order to
      distinguish between the efficiency of the two preparations. Rapid increases in
      EPA and DHA plasma concentrations can be demonstrated at all dosages during a 28
      day ingestion period. EPA accumulated more during ingestion of high than of low
      dosages of fish oil. DHA revealed almost identical increases and peak values in
      plasma concentrations in all subgroups. The present data demonstrate dose
      dependent increases of EPA concentrations whereas DHA plasma concentrations are
      comparable in all dosages investigated. Measurable EPA and DHA plasma
      concentration levels are inappropriate means to explain clinical effectiveness.
      These results were found in both commercially available fish oil preparations.
      Direct comparison of both preparations revealed no differences in
      bioavailability.

PMID- 1387232
TI  - Assessment and treatment of low back pain.

PMID- 1387233
TI  - Diagnosing low back pain.

PMID- 1387234
TI  - DNA as a solar dosimeter in the ocean.
AB  - Stratospheric ozone depletion may result in increased solar UV-B radiation to the
      ocean's upper layers and may cause deleterious effects on marine organisms. The
      primary UV-B damage induced in biological systems is to DNA. While physical
      measurements of solar UV-B penetration into the sea have been made, the effective
      depth and magnitude of actual DNA damage have not been determined. In the
      experiments reported here, UV-B-induced photoproducts (cyclobutane pyrimidine
      dimers) have been quantified in DNA molecules exposed to solar UV at the surface
      and at various depths in clear, tropical marine waters off Lee Stocking Island
      (23 degrees 45' N, 76 degrees 0.7' W), Exuma Cays, Bahamas. (14C)thymidine
      labeled DNA or unlabeled bacteriophage phi X174 DNA was placed in specially
      designed quartz tubes at various depths for up to five days. Following exposure,
      DNA samples were removed to the laboratory where UV-B-induced pyrimidine dimers
      were quantified using a radiochromatographic assay, and bacteriophage DNA
      inactivation by solar UV-B was assayed by plaque formation in spheroplasts of
      Escherichia coli. Pyrimidine dimer induction was linear with time but the
      accumulation of dimers in DNA with time varied greatly with depth. Attenuation of
      dimer formation with depth of water was exponential. DNA at 3 m depth had only
      17% of the pyrimidine dimers found at the surface. Bacteriophage phi X174 DNA,
      while reduced 96% in plaque-forming ability by a one day exposure to solar UV at
      the surface of the water, showed no effect on plaque formation after a similar
      exposure at 3 m. The data collected at the water's surface showed a "surface
      enhanced dose" in that DNA damages at the real surface were greater than at the
      imaginary surface, which was obtained by extrapolating the data at depth to the
      surface. These results show the sensitivity of both the biochemical (dimers) and
      biological (phage plaques) DNA dosimeters. DNA dosimeters offer a sensitive,
      convenient and relatively inexpensive monitoring system, having both biochemical
      and biological endpoints for monitoring the biologically effective UV-B flux in
      the marine environment. Unlike physical dosimeters, DNA dosimeters do not have to
      be adjusted for biological effectiveness since they are sensitive only to DNA
      mediated biologically effective UV-B radiation. Results of pyrimidine dimer
      induction in DNA by solar UV accurately predicted UV doses to the phage DNA.

PMID- 1387235
TI  - Parental and family well-being in families of children with Down syndrome: a
      comparative study.
AB  - The purpose of this study was to examine the effects of a child with Down
      syndrome on the individual functioning of both parents, marital functioning, and
      family functioning. Thirty-four families of children with Down syndrome were
      compared to 41 families with nondisabled children. Mothers and fathers in both
      groups completed a series of self-report measures. No significant differences
      were obtained between the two groups of families on any of the measures of
      individual, marital, or family functioning. The results of this study support a
      competence model in which parents may respond to the challenges associated with
      parenting a child with Down syndrome with resilience and adaptive functioning.

PMID- 1387237
TI  - [Interventional radiology in the treatment of acute and chronic mesenteric
      ischemia].
AB  - Radiologic revascularization procedures--i.e., percutaneous transluminal
      angioplasty (PTA) and fibrinolysis--are a valuable alternative to surgery in the
      treatment of stenoses and occlusions of the visceral vessels, that is the celiac
      tripod and the superior and inferior mesenteric arteries. We treated 32 patients,
      10 of them with acute mesenteric ischemia and 22 with chronic mesenteric ischemia
      and clinical signs of angina abdominis. Gruntzig or pre-shaped Cobra or Simmons
      balloons were employed (diameter: 5-7 mm, with variable length) when PTA was
      performed. Urokinase or rtPA was employed for fibrinolysis. In 3 cases acute
      mesenteric ischemia was not occlusive and could be successfully treated with
      papaverine infusion. In 7 cases, acute mesenteric ischemia was occlusive: in 5 of
      these patients it was successfully treated by PTA and/or fibrinolysis. Our
      results were positive in 80% of the cases, with remission of clinical signs in 4
      of 5 patients treated for acute mesenteric ischemia. In 22 patients with chronic
      mesenteric ischemia, 26 stenotic occlusions were observed at angiography and 22
      were treated with PTA, which was technically successful in 21 instances (early
      success rate: 85-95%). At 24 months, 10% of restenosis was observed. In our
      experience, PTA of the visceral district, possibly preceded by loco-regional
      infusion of fibrinolytic drugs, can be widely applied and yields excellent
      therapeutic results.

PMID- 1387236
TI  - [Intra-arterial urokinase in the treatment of acute thrombosis of the renal
      artery. A case report].

PMID- 1387238
TI  - Mechanisms and amelioration of acute renal allograft failure in the cyclosporine
      era.
AB  - The fairly wide-ranging spectrum of tactics under investigation for ameliorating
      acute renal allograft dysfunction caused by harvest/preservation-related
      ischemia, acute CsA nephrotoxicity, and acute immunologic crises reflect the fact
      that no single approach has emerged as universally useful for mitigating the
      vasomotor nephropathy produced by the combined effects of each of these vectors
      of vasomotor renal allograft injury. Given the clinical heterogeneity of patients
      and allografts, it is the author's bias that, in addition to careful donor and
      recipient hemodynamic management, induction immunosuppressive regimens should be
      individualized on the basis of allograft function in the immediate
      postreperfusion period (judged by rate of diuresis, intraoperative parenchymal
      tone, renal scan profiles, and rate of decline of serum creatinine concentration)
      as well as patient-specific immunologic and general medical risk factors.
      Promising laboratory and clinical investigations of such agents as calcium
      channel blockers, substances promoting intrarenal vasodilator vs. vasoconstrictor
      prostaglandin formation, and atriopeptins have the potential to provide
      clinically helpful options with regard to adjunctive therapy for ameliorating
      acute renal allograft dysfunction associated with INF and ACR.

PMID- 1387239
TI  - Use of transgenic animals to study disease models: hyperoxic lung injury and
      ischemic acute renal failure in "high SOD" mice.

PMID- 1387240
TI  - The HOME inventory: a new scale for families of pre- and early adolescent
      children with disabilities.
AB  - A preliminary form of a new version of the Home Observation for Measurement of
      the Environment (HOME) is presented. It is designed for use with families of
      children aged 10-15. The 80-item preliminary version of the Preadolescent HOME
      (PA-HOME) was field tested on 117 children with varying disabilities. The 80
      items were selected from a pool of over 250 items by means of several field tests
      and accompanying item analyses. Both factor analyses and item analyses were used
      to help pare down items and produce a scale with acceptable psychometric
      properties. The psychometric properties of the PA-HOME are quite similar to those
      reported for the other three versions of the HOME Inventory. It appears to be a
      reasonably reliable scale with moderate correlations with other measures of the
      family environment, such as SES, social support, and marital stability. It has
      low to moderate correlations with measures of child competence in this sample of
      children with disabilities. The correlations are of the same general magnitude of
      correlations between the Infant-Toddler, Early Childhood, and Middle Childhood
      versions of HOME in samples of younger children with disabilities.

PMID- 1387241
TI  - [Epidemiology of asthma in children and young adults in Algiers].
AB  - A sampling survey was carried out in Algiers among households to assess the
      frequency of chronic asthma in children and young people and to investigate the
      handicap resulting from this disease. 4,677 subjects younger than 25 years of age
      were registered, 47% of whom were children under 15. A report by households of a
      doctor's diagnosis of asthma was used to identify subjects with this disease from
      a direct face-to-face interviewing. The overall annual prevalence was 34.2 per
      thousand and the annual incidence was estimated as 3.1 per thousand. Except for
      children under 5 years of age which prevalence was 16 per thousand, the
      prevalence ranged from 34 to 41 per thousand for the other age groups. There was
      no significant difference between children and young adults for prevalence or
      incidence rates of asthma. The prevalence was two times greater in boys than in
      girls. On the other hand, the prevalence of asthma was 2.5 times greater in upper
      social class persons than in lower class persons. The proportion of severe
      handicaps was very low. But moderate handicaps resulting from asthma especially
      in the field of occupation were substantially frequent, 21% of asthmatics had a
      curtailed or adjusted occupation.

PMID- 1387243
TI  - Preclinical and clinical studies of macrophage colony-stimulating factor.

PMID- 1387242
TI  - The coagulative system in haemodialyzed patients: the relationship between the
      elderly and hypertrygliceridaemia.
AB  - The coagulative system has an important role on haemodialysis and on
      atherosclerosis genesis; in particular the platelets are key elements of the
      coagulation and of atherosclerosis phenomena. Alterations of the coagulative
      system and increase risk of developing atherosclerosis are reported in the aging.
      We in this paper, report the results obtained studying the influence of the
      interaction between the elderly and dyslipidemia on the coagulative system in
      haemodialyzed patients. The obtained data showed that the hypertriglyceridaemia
      in interaction with the elderly accelerates and increases platelet aggregation
      after stimulation by ADP, Epinephrine and Collagen. So, it is important to
      consider hypertriglyceridaemia and age as thrombogenic factors and
      atherosclerosis accelerating factors in haemodialyzed patients.

PMID- 1387244
TI  - Ondansetron: A new concept in the management of emesis. Proceedings from an
      investigators meeting. Seattle, Washington, September 1990.

PMID- 1387245
TI  - Pharmacology and preclinical antiemetic properties of ondansetron.
AB  - Ondansetron (GR 38032) has potent and highly selective antagonist properties at
      the 5-hydroxytryptamine (5-HT, serotonin) 5-HT3 receptor. The selectivity ratio
      for ondansetron on 5-HT3 receptors compared with actions on other
      neurotransmitter receptor types is greater than 1,000. The antiemetic properties
      of ondansetron have been determined in ferrets against the nausea and vomiting
      induced by cisplatin, cyclophosphamide, and whole-body radiation. Ondansetron
      (intravenous 0.01 to 0.1 mg/kg or subcutaneous 0.1 to 0.5 mg/kg) or
      metoclopramide (1.0 to 4.0 mg/kg) cause dose-dependent inhibitions of the
      vomiting induced by each of these procedures. Unlike ondansetron, the effects of
      metoclopramide are accompanied by moderate to marked behavioral depression. Since
      metoclopramide is 50 times more potent on dopamine D2 receptors than on 5-HT3
      receptors, the behavioral depression is likely due to profound blockade of
      dopamine receptors. The 5-HT3 receptors have been shown to be present
      peripherally on vagal afferent fibers and are densely located in the vomiting
      center of the hindbrain. The current hypothesis is that there may be both a
      peripheral and a central site of action for ondansetron and other 5-HT3
      antagonists. The lack of antagonist activity on dopamine and other non-5-HT3
      receptors indicates that, unlike metoclopramide, ondansetron will not cause
      extrapyramidal or other dose-limiting side effects.

PMID- 1387246
TI  - Phase I and other dose-ranging studies of ondansetron.
AB  - Phase I studies of intravenous (IV) ondansetron in cancer patients receiving
      emetogenic chemotherapy were designed to assess the degree of antiemetic
      protection and pattern of adverse events produced by ondansetron at various
      doses. In a study of 44 patients receiving various forms of chemotherapy
      (including cisplatin), ondansetron was administered in three IV doses 2 hours
      apart beginning 30 minutes prior to chemotherapy. Antiemetic efficacy was seen at
      all dose levels (0.04 mg/kg to 0.35 mg/kg), with 54% of patients experiencing no
      vomiting and 76% experiencing two or fewer vomiting episodes within the first 24
      hours. Overall, ondansetron was well tolerated, and no dose-limiting toxicity was
      observed. The most common adverse events were mild sedation, mild headache, and
      transient elevations of transaminases. In a second phase I study, 45 patients
      receiving cisplatin (median dose 100 mg/m2) were given ondansetron in three IV
      doses (range, 0.01 mg/kg to 0.48 mg/kg) 4 hours apart. There was no statistically
      significant difference in antiemetic efficacy among dose levels from 0.06 mg/kg
      to 0.48 mg/kg; however, there was a trend toward a decrease in the number of
      patients with failure of antiemetic protection at the higher exposures. Overall,
      44% of patients had no emetic episodes, and 81% of patients had two or fewer
      emetic episodes within the first 24 hours. The number and intensity of adverse
      events, of which headache was the most common, appeared to increase at the 0.48
      mg/kg dose level. A randomized double-blind study that compared three dose levels
      of ondansetron indicated that three doses of 0.15 mg/kg was superior in efficacy
      to three doses of 0.015 mg/kg, and not significantly different from three doses
      of 0.30 mg/kg. Dystonic reactions or akathisia were not noted in any study.

PMID- 1387247
TI  - Phase II trials of ondansetron with high-dose cisplatin.
AB  - Phase II trials of ondansetron were undertaken to assess the ability of this
      agent to control nausea and vomiting caused by specific chemotherapeutic agents,
      to establish the optimal number of doses and the most appropriate schedule of
      administration, to see if control could be improved by the use of continuous
      infusion, and to ascertain if the degree of efficacy and safety of ondansetron
      would warrant further investigations. In each of six multiplebolus trials,
      ondansetron was given at 0.15 mg/kg to 0.18 mg/kg intravenously for three doses,
      beginning 30 minutes prior to cisplatin. No patient had received prior cancer
      chemotherapy. Overall, 48% of patients experienced no emesis, and 71% had zero to
      two emetic episodes after receiving cisplatin doses of 100 mg/m2 or greater.
      Comparable antiemetic control was seen with all schedules studied. Three
      additional trials assessed the effect of the number of doses of ondansetron on
      antiemetic effectiveness. A single dose gave complete protection in 25% of
      patients and three doses gave a 50% no-emesis rate. Complete control was not
      improved when six doses of ondansetron were given. Efficacy rates with multiple
      bolus therapy and continuous infusion over 24 hours were similar. Side effects
      were mild and reversible in all trials, and there were no remarkable differences
      in adverse events among different schedules or numbers of doses. The complete and
      major control rates observed show that ondansetron is as effective as or more
      effective than metoclopramide in controlling cisplatin-induced emesis.

PMID- 1387248
TI  - Comparative trials of ondansetron versus metoclopramide in the prevention of
      acute cisplatin-induced emesis.
AB  - A logical outgrowth of the early clinical success with ondansetron in phase I and
      phase II trials has been an interest in comparative antiemetic trials using
      conventional agents. Metoclopramide is generally acknowledged to be the single
      most effective conventional drug for the prevention of acute cisplatin-induced
      emesis and, therefore, was considered an appropriate agent for inclusion in
      comparative trials with ondansetron. Three phase III trials comparing
      metoclopramide with ondansetron for the prevention of acute nausea and vomiting
      associated with cisplatin administration have been completed to date. One was a
      single-blind, parallel-group trial conducted in the United States, and the other
      two were double-blind, crossover trials performed in Europe. The efficacy results
      of these studies demonstrated either a consistent trend or clear superiority of
      ondansetron in comparison with metoclopramide. Treatment failure consistently
      developed much later with ondansetron than with metoclopramide. Less antiemetic
      toxicity was noted with ondansetron. With the exception of headache, there was a
      lower incidence of neurologic adverse events in the ondansetron group. No
      dystonic reactions were observed with ondansetron in any of the trials. In all
      three trials, patients expressed greater overall satisfaction with ondansetron
      for emesis control.

PMID- 1387249
TI  - Antiemetic activity of ondansetron in cancer patients receiving non-cisplatin
      chemotherapy.
AB  - The emetogenic properties of chemotherapeutic agents differ in terms of the
      frequency, intensity, time of onset, and duration of vomiting and nausea. As the
      effects of antiemetic agents in the control of emesis induced by different
      chemotherapeutic agents could differ, new antiemetics must be tested against a
      variety of chemotherapy challenges. In many non-cisplatin chemotherapy
      situations, a partly or totally oral schedule of antiemetic administration may be
      preferable. The selective 5-hydroxytryptamine (5-HT3)-receptor antagonist,
      ondansetron, has been shown to be a safe, effective, and well-tolerated
      antiemetic in the prevention of nausea and vomiting from several non-cisplatin
      chemotherapies. In randomized studies, ondansetron has compared favorably with
      metoclopramide in patients receiving cyclophosphamide-containing chemotherapy
      regimens.

PMID- 1387250
TI  - The use of ondansetron in patients receiving multiple-day cisplatin regimens.
AB  - The control of nausea and vomiting in patients receiving multiple-day cisplatin
      chemotherapy has remained difficult, even with the use of combination antiemetic
      regimens containing metoclopramide. Although these patients receive a lower daily
      dose of cisplatin, the emetogenic potential remains high. In addition, many of
      the patients receiving multiple-day cisplatin regimens are young (eg, testicular
      cancer patients) and, therefore, have particular problems with the extrapyramidal
      side effects associated with metoclopramide. Studies show that ondansetron, used
      as a single antiemetic agent, is effective, safe, and well tolerated in the
      control of nausea and vomiting in patients receiving multiple-day cisplatin
      regimens.

PMID- 1387251
TI  - Toxicity and side effects of ondansetron.
AB  - The safety of ondansetron has been carefully evaluated through laboratory studies
      and clinical trials. Preclinical studies demonstrated that there is no end-organ
      toxicity in rats and dogs administered ondansetron doses 30 to 100 times those
      used in humans. At near-lethal doses of ondansetron, animals developed subdued
      activity, ataxia, and convulsions. Modest transient increases in serum
      transaminase values were observed. Concurrent administration of ondansetron with
      chemotherapy had no effect on tumor response in animals. The clinical safety of
      ondansetron has been evaluated in more than 2,500 cancer patients who received
      intravenous doses as large as 1.5 mg/kg. In adult patients receiving single-day
      chemotherapy, the incidence of adverse events was 36% with ondansetron (n = 647)
      and 50% with metoclopramide (n = 498). Diarrhea occurred in 9% of ondansetron
      patients and 19% of metoclopramide patients. Headache occurred in 14% of
      ondansetron patients and 8% of metoclopramide patients. Extra-pyramidal symptoms
      were reported in none of the ondansetron patients and 5% of the metoclopramide
      patients. The incidence of vascular occlusive events and seizure disorders was
      nearly identical with ondansetron and metoclopramide and similar to the cancer
      population in general. In a group of 209 pediatric patients receiving
      chemotherapy, the incidence of adverse events was 19% with ondansetron. Serum
      transaminase values increased significantly in 6% to 8% of ondansetron patients
      and 2% of metoclopramide patients. There was no apparent relationship between the
      cumulative dose of ondansetron administered and the incidence of increased
      transaminase values. However, there was an apparent relationship between the
      cumulative dose of cisplatin administered and the incidence of transaminase
      abnormalities. These data demonstrate that ondansetron is better tolerated than
      metoclopramide and is safe for intravenous administration to pediatric and adult
      patients receiving chemotherapy.

PMID- 1387252
TI  - Rationale for combination antiemetic therapy and strategies for the use of
      ondansetron in combinations.
AB  - The identification of several safe and effective agents for the control of
      chemotherapy-induced nausea and vomiting has prompted an intensive effort to
      develop combination antiemetic regimens. The principal rationale for development
      of drug combinations is the potential for blocking different types of
      neurotransmittor receptors controlling the emetic process. Studies have shown
      that the combination of a neurotransmitter receptor blocker, a corticosteroid,
      and a benzodiazepine improves antiemetic efficacy, lessens side effects, and
      decreases the length of treatment and the number of drug administrations.
      Ondansetron appears to be an excellent antiemetic for use in combination programs
      because of its highly selective, 5-hydroxytryptamine (5-HT3)-blocking properties
      and its proven single-agent effectiveness and safety. Preliminary data show that
      ondansetron can be combined with dexamethasone safely with enhanced antiemetic
      results. Ondansetron merits further study in combination antiemetic programs.

PMID- 1387254
TI  - Ondansetron metabolism and pharmacokinetics.
AB  - Hepatic oxidative metabolism accounts for more than 95% of ondansetron clearance
      from the body. The major excreted metabolites are conjugates of 7-hydroxy or 8
      hydroxyondansetron, which appear to contribute little to the activity of the
      parent drug. Ondansetron plasma clearance averages approximately 0.45 L/h/kg, is
      similar in young male volunteers and cancer patients undergoing cisplatin-based
      chemotherapy, and does not change significantly with repeated dosing. Clearance
      decreases with increasing age, whereas volume of distribution remains unchanged.
      The result is an increase in mean plasma half-life from 3.5 hours in young
      volunteers (18-40 years) to 5.5 hours in volunteers over 75 years of age.
      Clearance and volume of distribution are higher in young (7-12 years) cancer
      patients, resulting in a mean plasma half-life of 2.5 hours. Plasma clearance is
      slightly slower in females. Ondansetron clearance decreases and half-life
      increases in patients with severe hepatic insufficiency. Clearance may be
      enhanced in patients receiving known hepatic enzyme inducers. Because of large
      intersubject variability in clearance and the relative safety of ondansetron,
      adjustments in ondansetron dosing based on age or gender alone are not
      recommended. Ondansetron is rapidly and completely absorbed when administered as
      a tablet. A relationship exists between control of emesis and the area under the
      plasma concentration-time curve for ondansetron. All data collected to date
      support the thesis that ondansetron is a competitive antagonist of the 5
      hydroxytryptamine (5-HT3) receptor in humans.

PMID- 1387253
TI  - The delayed-emesis syndrome from cisplatin: phase III evaluation of ondansetron
      versus placebo.
AB  - Cisplatin may evoke both an acute emetic response during the first 24 hours
      following treatment and a less well-recognized syndrome of delayed emesis. While
      delayed emesis is usually less severe in terms of frequency of vomiting episodes,
      the problem continues to result in significant morbidity. In comparison with
      acute emesis, the exact pathogenesis of the delayed emesis syndrome remains
      unclear. Although a combination of oral metoclopramide and dexamethasone is
      effective in many patients in preventing delayed emesis, almost 50% continue to
      experience at least one emetic episode when treated with this regimen. A phase
      III multicenter study has evaluated oral ondansetron versus placebo in the
      prevention of the delayed-emesis syndrome in 50 patients during days 2 through 5
      following high-dose cisplatin administration. Although the daily rates of
      complete emetic control, failure, and control of nausea favor ondansetron, this
      trial is statistically inconclusive in establishing efficacy of ondansetron as a
      single agent in the prevention of delayed emesis. Ondansetron was well tolerated
      in the dose and schedule used.

PMID- 1387256
TI  - Socio-economic circumstances and functional abilities of elderly black persons in
      the Orange Free State.
AB  - A community-based epidemiological study was undertaken to determine the health
      profile of the elderly black population in the Orange Free State. Four hundred
      elderly blacks were randomly selected from 10 towns. Questionnaires on past and
      present illnesses, socio-economic circumstances (including formal education) and
      daily activities were completed. Most of the elderly blacks received a state old
      age pension and 15.3% were still economically active. We found that 63% of the
      subjects were illiterate and that 31% did not live with their children. Inability
      to perform any of six activities was found in 3.2%. In view of the high number of
      elderly persons living alone, we feel that the development of support services
      should receive urgent attention.

PMID- 1387255
TI  - Treatment of autoimmune diseases with intravenous gammaglobulin.

PMID- 1387257
TI  - A standing/sitting pelvic tilt chair--new hope for back-weary surgeons?

PMID- 1387258
TI  - [The incidence of ischemic heart disease and its risk factors in 20- to 54-year
      old male workers in physical and intellectual jobs].
AB  - The low incidence of coronary heart disease (CHD) was established in the course
      of a one-stage epidemiological examination of 2562 men aged 20-54 years (a random
      sample from an open city population). It was found to be associated with an
      insignificant prevalence of lipid metabolism abnormalities (excluding
      hypoalphacholesterolemia) and did not depend on the nature of labour (4.3% among
      white collars and 4.4% among blue collars). The incidence of overweight and high
      AP turned out approximately identical, whereas tobacco-smoking,
      hypercholesterolemia and hypertriglyceridemia were mostly recorded in blue
      collars. The prevalence of CHD and its risk factors increased with age, excluding
      tobacco-smoking. In the latter case, it reduced with age.

PMID- 1387259
TI  - [Ways to improve the teaching of internal diseases based on the use of computer
      technology].

PMID- 1387261
TI  - [One of the basic problems of hepatology today].

PMID- 1387260
TI  - [Viral hepatitis B in women during lactation].

PMID- 1387262
TI  - [The role of a lesion of the gastrointestinal tract in the origin of urticaria].
AB  - The relations between urticaria and various diseases of the gastrointestinal
      tract (GIT) are under discussion. The disturbances of the gall bladder and
      biliary vessels, liver diseases, and disorders of the stomach are most often
      among those diseases. The main role is played by disturbances of upper GIT
      motility, bacterial and viral infection. It is necessary that in the treatment of
      GIT lesions-related urticaria, disturbances of the GIT may be corrected.

PMID- 1387263
TI  - Monoclonal antibody-based enzyme-linked immunosorbent assays (ELISA) for the
      measurement of vitamin K-dependent protein S: the effect of antibody
      immunoreactivity on plasma protein S antigen determinations.
AB  - Two monoclonal antibodies (Mabs) specifically directed to human protein S (PS) -
      named 5E9E9 and 3B10.25 - were produced and their properties compared to those of
      2 previously characterized anti-PS-Mabs (HPS-2 and S10). 3B10.25, similar to S10,
      was directed to the calcium-free conformation of PS and had virtually identical
      affinity for free and C4b-binding protein (C4b-BP)-bound PS; 5E9E9 similar to HPS
      2, had no calcium-dependency and was selectively directed to free PS. All Mabs
      were equally reactive to freshly purified and thrombin-cleaved PS. To evaluate
      the influence of C4b-BP bound PS on PS antigen determinations, ELISA systems
      employing the four Mabs individually as capture antibody (Ab) and peroxidase
      conjugated polyclonal anti-PS IgG as detecting Ab were developed and compared to
      immunoelectrophoresis (EIA) and to an ELISA employing polyclonal anti-PS IgG as
      capture and detecting Ab, in the determination of PS in purified systems and in
      plasma. With all the ELISAs there was parallelism of dilution curves obtained
      with normal plasma and purified PS; however, supplementation of plasma with
      purified C4b-BP resulted in loss of parallelism when employing the Mabs directed
      to free PS as capture Ab. Influence of high C4b-BP on PS antigen determinations
      was confirmed in a series of plasma samples from patients with C4b-BP levels
      ranging from 70% to over 200%. Compared to the values obtained with the S10- or
      3B10.25 - based ELISAs - which were similar despite a 10-fold difference in
      sample dilution - plasma PS was underestimated by the ELISAs employing 5E9E9 or
      HPS-2 while it was overestimated by EIA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387264
TI  - Release of thromboxane A2 and beta-thromboglobulin during in-vivo plug formation
      following standardized skin incisions: effect of a moderate fish intake.
AB  - This paper describes a controlled study of the effects of a fish supplement on
      haemostasis. This was evaluated by measuring bleeding times from skin incisions,
      the volume of the emerging blood, the number of platelets taking part in the
      formation of the haemostatic plug (platelet retention), and the release of
      thromboxane B2 and beta-thromboglobulin in volunteers, before and after consuming
      a daily supplement of 100 g of fish (n = 20) or meat (n = 20) paste for 6 weeks.
      The fish supplement decreased the amount of thromboxane B2 released per platelet
      incorporated into the plug. Despite this, the skin bleeding times were hardly
      changed. There was also no difference in platelet retention, which was consistent
      with there being no difference in the release of beta-thromboglobulin. These
      results suggest that in the effect of marine diets on haemostasis, a reduced
      vascular reactivity plays a more important role than decreased plug formation.

PMID- 1387265
TI  - [Laparoscopic r(evolution)?].

PMID- 1387267
TI  - [Hip prostheses in Murmansk].

PMID- 1387266
TI  - [Laparoscopic closure and tegmentation of perforated ulcer].
AB  - Laparoscopy is fully recognized for diagnosis and even treatment of various acute
      abdominal conditions. In a 42-year-old woman with intense lower abdominal pain,
      laparoscopy revealed a perforated peptic ulcer. The ulcer was closed and patched
      with omentum and the abdomen was irrigated, all by laparoscopic techniques.
      Except for a minor wound infection recovery was uneventful.

PMID- 1387268
TI  - [Handling and decisions by the authorities of reported occupational tendon
      injuries of the upper extremities. Occupational diseases' registry E6b].
AB  - The aim of this investigation was to show how the Danish National Social Security
      Office, (the department of industrial injuries insurance (NSS)), handles the
      cases and makes the final decisions concerning the diseases in tendons in the
      upper extremity belonging to the list of occupational disorders in the Danish
      Workers' Compensation Act. Five hundred and nineteen notified cases were followed
      up until the final solution and eventual compensation for permanent injury and
      loss of earning capacity. Two hundred and twenty-six cases had to be excluded
      because the criteria in the list of Occupational Disorders concerning unusual
      work and complete or partial inability to work were not fulfilled. Sixty-seven
      commenced work again after the notification and forty four did not reply to the
      NSS correspondence. One hundred twenty-seven had to be eliminated for other
      reasons. Fifty-five cases could be further investigated according to the workload
      criteria. fourteen were accepted and forty-one were rejected. Eight of these were
      paid a total compensation for permanent injuries amounting to 200,000 DDK and a
      capitalized compensation for loss of earning capacity amounting to 1,000,000 DDK.
      The notified diseases occurred among unskilled workers in their forties, equally
      frequently in men and women. It takes a long time to obtain the answers to NSS
      correspondence from doctors as well as the injured persons and therefore a total
      handling time of up to one year has to be expected. Our conclusion is that it is
      difficult to have these diseases accepted as being caused by the work because the
      criteria on the list about "unusual work" and "complete or partial inability to
      do normal work" exclude many cases from acceptance. Probably the criteria for
      workload should be changed so that it is based on an objective goal for the
      workload and the movements to a greater extent compared with the exposure time.
      Doctors who report the diseases should be more precise in the notified diagnosis,
      symptoms and the workload responsible.

PMID- 1387269
TI  - [Hypercalcemia during immobilization and prolonged anuria treated with disodium
      clodronate].
AB  - Severe hypercalcaemia was observed during prolonged anuria and prolonged
      immobilization in a previously healthy 34 years old male after a severe trauma
      caused by a traffic accident. Other causes of the hypercalcaemia were evaluated,
      and even though granulomas of unidentified nature were found in the liver after
      partial resection due to traumatic rupture the immobile state was concluded to be
      the major cause. A maximum calcium value of 4.44 mmol/l was seen after 10 weeks
      immobilization. The patient was treated with daily dialysis and, even though the
      calcium content in the dialysis fluid was reduced, only a minor effect was seen
      on the calcium level. After eight weeks of hypercalcaemia, the patient was
      treated with disodium clodronate intravenously 400 mg for daily five days.
      However, the calcium level was not normalized and the treatment was repeated with
      a further reduction in the calcium level. If immobilization is a major
      contributory factor to hypercalcaemia, disodium clodronate seems to be a safe and
      effective treatment.

PMID- 1387270
TI  - Hematological alterations in kittens induced by 6 and 12% dietary propylene
      glycol.
AB  - Soft-moist cat foods containing 6-13% propylene glycol (PG) induce Heinz body
      formation and decreased red blood cell (RBC) lifespan in adult cats in a dose
      dependent manner. Since kittens eat relatively more food/kg of body weight and
      must expand their blood volume in addition to replacing senescent RBC, the
      hematologic dyscrasia associated with consumption of PG-containing diets may be
      exaggerated. To test this hypothesis 21 kittens were divided into 3 groups of 7
      each and fed diets containing, 0,6 or 12% PG for 13 w. A dose-related increase in
      Heinz bodies occurred in the 6 and 12% PG groups within 2 w and persisted
      throughout the study. Although only slight changes occurred in hematocrit,
      hemoglobin and red blood cell (RBC) count, punctate reticulocytes increased
      significantly in the 6 and 12% PG groups indicating accelerated erythropoiesis.
      Mean RBC survival was decreased in the 6 and 12% groups by 44% and 63%
      respectively when compared to the control group. The increase in reticulocyte
      count and reduction in RBC lifespan was greater than observed in adult cats. The
      greater effect in kittens may be due to greater PG intake and not to an inate
      susceptibility of kitten RBC to PG.

PMID- 1387271
TI  - [Eosinophilic gastroenteritis with serosa involvement. A rare differential
      diagnosis of ascites].
AB  - A 21 year old caucasian male suffered for 14 days from cramping abdominal pain,
      associated with nausea and vomiting. 6 weeks later he was admitted to our
      hospital because of rapidly increasing ascites. Further examinations led to the
      following decisive findings: Marked eosinophilia in the white cell count; marked
      eosinophilia in protein rich ascitic fluid; infiltration of serosal layer with
      eosinophils; no evidence for parasites in blood, faeces and ascites in multiple
      probes; no evidence for malignant or rheumatoid disease. Histology and cytology
      of probes obtained at laparoscopy led to the diagnosis of eosinophilic
      gastroenteritis with ascites. After low dose prednisolone therapy we observed a
      complete relief of symptoms and ascites disappeared.

PMID- 1387272
TI  - [Significance of the ulcer vessel in acute ulcer hemorrhage--value of local
      endoscopic therapy in combination with endoscopic Doppler ultrasound].
AB  - The acute ulcer hemorrhage is one of the most frequent diagnoses in
      Gastroenterology. In addition to the active hemorrhage the visible ulcer vessel,
      even if not bleeding at present, is one of the most important prognostic
      criteria. Numerous controlled studies have shown that with this sign recurrent
      hemorrhages will occur in up to 81%, resulting in emergency surgery in up to 56%
      with an associated mortality of up to 21%. By a meta-analysis we could show that
      prophylactic endoscopic therapy can significantly reduce both the rate of
      recurrent hemorrhage as well as emergency surgery. If the endoscopic doppler is
      used as well, as diagnostic as well as follow-up examination, the effectiveness
      of endoscopic treatment is greatly improved. The numbers we present show that
      active local endoscopic therapy should be undertaken in a visible ulcer vessel.

PMID- 1387273
TI  - [Change in the income status of the disabled after introduction of long-term care
      insurance].
AB  - Up to the present time, long-term-care needs in the Federal Republic of Germany
      have only been covered to a limited extent through health insurance. The needs of
      the majority of those requiring long-term care must be covered from their pension
      funds or acquired wealth. This often does not suffice, which results in those
      needing long-term care becoming recipients of social assistance. The introduction
      of a long-term-care insurance should bring an end to this situation, which is
      considered unacceptable. At present, two competing schemes for covering the
      social risk of long-term care are being discussed: a social security insurance
      and a private insurance. When comparing the planned benefits under consideration,
      the social security insurance is more favorable in regards to nursing-home
      treatment, as well as with at-home care and benefits in kind. The private
      insurance is more favorable when considering nursing-home treatment and monetary
      benefits. If the private insurance is adopted, over 31% of those formerly relying
      on nursing-home care would no longer need social assistance. In the case of
      social security insurance, almost 46% would no longer require social assistance.
      Most of the remaining individuals requiring social assistance would be women.

PMID- 1387274
TI  - Disability in Western Highlands Province.
AB  - During late 1987 and early 1988 the Mount Hagen Handicapped Children's Centre (as
      it was then known) set out to determine if substantial numbers of persons with
      disabling conditions lived within 15km of Mount Hagen town. The investigation
      located 1408 persons, deemed by themselves, family members or neighbours to have
      a disability.

PMID- 1387275
TI  - Necrotizing crepitant cellulitis of the abdominal wall following a caesarean
      section and subsequent hysterectomy.
AB  - A case report of necrotizing crepitant cellulitis of abdominal wall following
      caesarean section is presented. Because of intense haemorrhage it was namely
      necessary to perform additional hysterectomy and bilateral hypogastric artery
      ligation. Serious wound infection and sepsis were successfully treated by
      administration of antibiotics and repeated deep incisions.

PMID- 1387276
TI  - [Study of the epidemic significance of noncultivated forms of Vibrio cholerae by
      the polymerase chain reaction].
AB  - A specific method of the isolation of the cholera toxin gene by the directional
      amplification of DNA in the polymerase chain reaction (PCR) has been developed.
      The product of this reaction has a molecular weight of 440 sequence pairs and is
      a DNA fragment located on the A-subunit of V. cholerae gene vct. The sensitivity
      of the method permits the detection of one bacterial cell in the reaction
      mixture. The method is effective when V. cholerae purified DNA, cell lysates and
      the DNA of total microflora isolated from the water of natural springs are used.
      The study of water samples from natural water bodies by the method of PRC has
      revealed cholera toxin genes of V. cholerae noncultivated forms ni 5 out of 7
      water samples taken from natural water bodies at the regions of Azerbaijan
      endemic for cholera and made it possible to evaluate the number of V. cholerae.
      The prospects of using PCR for the control of the epidemiological situation in
      regions endemic for cholera are discussed.

PMID- 1387277
TI  - [Self-maintenance of foci of bovine leptospirosis].
AB  - The relationship between the rate of cattle infection with leptospirosis and the
      total number of livestock at cattle-breeding farms has been established. The
      annual dynamics of this infection has been found to give two morbidity rises
      among the animals, occurring not due to their contacts with the natural foci of
      leptospirosis, but as a consequence of the animal vertical and horizontal
      "circulation". The mechanisms of self-maintenance of the foci of leptospirosis
      among cattle are discussed.

PMID- 1387278
TI  - [Laparoscopic surgery--the revolution in gallstone treatment].
AB  - The treatment of gallbladder disease is revolutionized by laparoscopic
      cholecystectomy (LCHE). Less pain postoperatively, earlier mobilization and a
      fascinating cosmetic result as well as a definitive cure of the disease have led
      to a fast acceptance by patients and doctors. From March 1990 to March 1991 we
      have performed 250 LCHE. Only 5 times we had to switch to the conventional
      procedure. 5 complications (1 lesion of the common bile duct, 2 biliary effusion,
      1 abscess formation, 1 bleeding) were treated by laparotomy without further
      morbidity or lethality. Our rate of gallbladders operated by laparoscopy has
      increased from 35% in 1990 to 75% in 1991.

PMID- 1387279
TI  - Perceptions of parents of handicapped children concerning nurses and the health
      care system as it affects them.
AB  - Because of the change in mandate for Home Care Programs across Alberta, new cases
      of children with handicaps are now being assessed by nurses. Social workers,
      through the Handicapped Children's Services program, have traditionally been the
      ones to assess these children. This is a very new area for nurses and there is
      much to learn. Even less is known about the parents' perspective in working with
      families in community. As both a nurse working in the community and a parent of a
      child with special needs I see many of the issues from two sides. This study
      seeks to find out more about parents' feelings and views regarding nursing and
      the health care system. This knowledge is helpful to nurses working with these
      families as they strive to understand, communicate and build a helping
      relationship.

PMID- 1387280
TI  - [Infrequent cause of bilateral obstructive uropathy].
AB  - Muscular haematoma of the straight muscles of the abdomen are very rare to
      observe and, although there is a possibility of the haematoma extending to the
      retroperitoneum, they very rarely cause oligoanuria by compression of the urinary
      tract. Presentation of one case of spontaneous haematoma of the straight muscles
      of the abdomen with urologic damage by ureteral compression inducing oligoanuria
      and bilateral ureterohydronephrosis.

PMID- 1387281
TI  - Steroid therapy in Huntington's disease.

PMID- 1387282
TI  - Dilated cardiomyopathy associated with taurine deficiency in the domestic cat:
      relationship to diet and myocardial taurine content.

PMID- 1387283
TI  - Mechanism of the modulation of murine peritoneal cell function and mast cell
      degranulation by low doses of malathion.
AB  - Malathion is a widely used organophosphate pesticide that modulates immune
      function at noncholinergic doses. Previous studies showed that this alteration in
      immune function was the result of enhanced macrophage function. In the present
      study, the effects of low doses of purified malathion (as low as 0.25 mg/kg
      malathion) administered orally to mice enhanced the respiratory burst of
      peritoneal cells. Microscopic examination of the peritoneal cells showed that
      mast cells were degranulated within 4 hr after malathion administration. The
      amount of beta-hexosaminidase, an enzyme released upon immunologic degranulation
      of mast cells, in the peritoneal lavage fluid of malathion-treated mice was also
      significantly elevated with 4 hours after malathion administration. Treatment of
      RBL-1, a rat basophilic cell line, cells with malathion, parathion or paroxon in
      vitro also led to the release of beta-hexosaminidase with paraoxon being the most
      potent. Further examination of the peritoneal cells of malathion-treated mice
      showed that the percentage of phagocytic peritoneal cells ingesting mast cell
      granules and the number of granules ingested per cell were elevated. These data
      suggest that malathion may enhance the respiratory burst of peritoneal cells
      through degranulation of peritoneal mast cells and the subsequent exposure to
      peritoneal cells to mast cell mediators.

PMID- 1387285
TI  - Platelet reactivity to "in vitro" allergen challenge in asthmatic patients.
AB  - Platelet involvement in inflammation and allergic states is now well documented.
      In fact, it has been suggested that platelets can be triggered by either
      activated cells as monocytes and macrophages or by allergen itself. This latter
      possibility is still a matter of controversy. In this study we analysed platelet
      "in vitro" response to allergen, by optical aggregation technique, in 25
      asthmatic patients, being 20 atopic and 5 non atopic patients. Platelet
      aggregation response to epinephrine, ADP, collagen and arachidonic acid was
      studied in all patients. In addition, allergen was added to platelet rich plasma
      and platelet reactivity was recorded both before and after stimulations with
      collagen. Platelet aggregation studies confirmed and abnormality of ADP induced
      platelet aggregation, that exhibited great variability among patients. In most
      cases this defect was the only one found in asthmatic patients and it should be
      further analysed. Results also showed a nonspecific response to allergen when
      dissolved in glycerol. This was due to glycerol rather than to allergen, since
      lyophilized allergen did not affect platelets, and glycerol added to platelet
      rich plasma induced the same type of curve. So, allergen by itself does not imply
      platelet aggregation. Experiments with IgE did not provoke either platelet
      agglutination or platelet aggregation. Furthermore, previous incubation with
      allergen immediately before collagen induced aggregation did not significantly
      change platelet response. This study allows the conclusion that platelet
      reactivity to allergen contact must be an expression of multicellular cooperation
      rather than a direct effect on platelet IgE receptors stimulation.

PMID- 1387286
TI  - Neutrophil chemiluminescence following exposure to formaldehyde in healthy
      subjects and in patients with contact dermatitis.
AB  - 13 formaldehyde-sensitive contact dermatitis patients and 5 healthy subjects were
      exposed to formaldehyde (FM) at a concentration 0.5 mg/m3, in an exposure chamber
      for 2 hours. There was no significant decrease of the ventilatory parameters
      either in healthy subjects or in contact dermatitis patients following the
      exposure Bronchial hyperreactivity to histamine (PC20) increased in one healthy
      and two patients with contact dermatitis. Neutrophils were isolated from whole
      venous blood before the test and 30 minutes and 24 hours after the exposure. All
      subjects with allergic contact dermatitis had chemiluminescence higher before the
      FM provocation in a comparison with the healthy ones. It increased significantly
      30 minutes post the exposure and was much higher 24 hours after the exposure in
      the comparison with the neutrophil chemiluminescence before the test.

PMID- 1387284
TI  - Effects of the immunomodulator diacetyl-splenopentin on antigen-induced arthritis
      in rabbits.
AB  - Long-term treatment with the immunomodulator diacetyl-splenopentin reduces the
      severity of chronic joint inflammation and cartilage destruction in rabbits with
      antigen-induced arthritis. The level of specific antibodies as well as specific
      and non-specific cell-mediated immune reactivities including the proliferative
      response of spleen lymphocytes to cartilage proteoglycans in treated animals are
      lower than in untreated arthritic rabbits. Moreover, suppressor cell activity,
      which normally decreases during the early phase of inflammation, is enhanced and
      hyperreactive helper cell potential is reduced. These findings suggest that
      treatment with diacetyl-splenopentin normalizes the immune regulation, which is
      disturbed in the early phase of inflammation. This might result in a depression
      of the hyperreactive immune system including the autoimmunity developed against
      cartilage. Lowered immune reactivity in the joint in turn reduces the severity of
      chronic joint inflammation.

PMID- 1387288
TI  - A new classification of left ventricular geometry in patients with cardiac
      disease based on M-mode echocardiography.
AB  - M-mode echocardiograms of 202 cardiac patients were studied with respect to the
      pattern of left ventricular (LV) geometry. Patients with normal LV mass and
      volume were separated from those who had LV hypertrophy or enlargement on the
      basis of LV mass and volume indexed to body surface area. The relative wall
      thickness that is currently used to classify LV hypertrophy/enlargement was found
      to be inadequate for differentiating between concentric and eccentric types of LV
      hypertrophy. A new M-mode echocardiographic classification is therefore proposed
      that accurately separates the different types of LV enlargement; it also allows
      identification of patients who have chronically dilated left ventricles at the
      expense of thin walls and thus have normal LV mass.

PMID- 1387287
TI  - Short- and long-term efficacy and safety of flecainide acetate for
      supraventricular arrhythmias.
AB  - This report summarizes efficacy and safety data on the use of flecainide acetate
      for supraventricular arrhythmias. For this purpose, 60 original articles were
      identified by a literature search representing data from 1,835 treatment courses.
      In 18 trials, flecainide was administered intravenously; in 19, orally; and in
      23, both forms of therapy were applied. There were 5 placebo-controlled and 12
      comparative studies, whereas data from uncontrolled studies were represented in
      43 articles. Short-term flecainide administration terminated atrial fibrillation
      in 65% of attempts and terminated atrial flutter in 28%. The drug was effective
      during long-term therapy for atrial fibrillation in 49% of patients, with similar
      efficacy rates in 11 comparative trials and in 16 uncontrolled studies. In
      randomized, placebo-controlled studies in patients with paroxysmal atrial
      fibrillation, flecainide was shown to reduce significantly the number of attacks,
      to prolong the time between attacks, and to improve quality of life. In patients
      with atrioventricular (AV) reciprocating tachycardias, acute drug administration
      was successful in 72%; 83% of patients with AV nodal reentrant tachycardias and
      74% exhibiting arrhythmias associated with the Wolff-Parkinson-White syndrome
      responded acutely. During long-term therapy, efficacy rates were 70%, 78%, and
      69%, respectively. Ectopic atrial tachycardia responded in 86% and 95% of
      patients treated with flecainide acutely or chronically. Data concerning drug
      related side effects were available for 1,794 of 1,835 treatment courses (98%).
      Overall, 352 of 1,794 patients (20%) reported at least one non-cardiac or cardiac
      adverse experience.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387289
TI  - Tensile strength of orthodontic brackets bonded directly to fluorotic and
      nonfluorotic teeth: an in vitro comparative study.
AB  - Information related to bonding of orthodontic brackets to fluorotic teeth is
      scanty. The purpose of this study was to compare, in vitro, the tensile bond
      strength and the bond failure site of brackets bonded directly to fluorotic and
      nonfluorotic teeth. The etching patterns were also evaluated. The study involved
      26 teeth classified as score 3 and 4, and 26 as score 0 with the Thylstrup and
      Fejerskov's (TF) fluorosis index. In addition to the clinical classification,
      difference in the concentration of fluoride in the teeth was verified by acid
      etching. Brackets were bonded with a composite resin after etching the enamel
      surface with 40% phosphoric acid for 60 seconds. Tensile bond strength was
      determined with an Instron testing machine. The bond failure site was assessed by
      the percentage of residue cement on the tooth surface after debonding and the
      etching pattern by SEM. The mean concentration of fluoride was 2888.5 ppm (SD
      1081.7) in the fluorotic teeth and 1227.1 ppm (SD 526.3) in the nonfluorotic
      teeth. The mean bond strength was 7.8 N/mm2 (SD 1.47) for the fluorotic teeth and
      8.6 N/mm2 (SD 2.19) for the nonfluorotic teeth. The difference between the means
      for bond strength was not statistically significant (p greater than 0.05). Bond
      failure site was primarily at the bracket-adhesive interface. The mean percentage
      of adhesive on the enamel surface after debonding was 70% (SD 25.90) for the
      fluorotic teeth and 75% (SD 24.66) for nonfluorotic teeth. The difference in the
      means was not statistically significant (p greater than 0.05).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1387290
TI  - Relations between sex hormone level and characters of hair and skin in healthy
      young men.
AB  - Total testosterone and dihydrotestosterone in blood serum as well as free
      testosterone in saliva were determined by radioimmunoassay in 110 healthy young
      men. The results were compared with the development of terminal hair on the trunk
      and limbs, with the disposition to balding and with the disposition to acne. No
      significant correlations were found between terminal hair development and
      absolute androgen levels; however, some significant values were observed in the
      case of the metabolic rate of dihydrotestosterone/testosterone and the proportion
      of free to total testosterone. The disposition to balding also correlates
      positively with the latter ratio. Yet the absolute serum androgen concentrations
      in men with a disposition to balding is lower than in men with no reduction of
      scalp hair. The widespread assumption that androgen levels are in general
      elevated in bald-trait men must therefore be rejected. In accordance with this
      finding, men with a disposition to balding are morphologically (with regard to
      anthropometric measures) no more masculine than those with good scalp hair
      growth. When body build and age are taken into consideration, the relations
      between terminal hair and androgen ratio are also problematical. No relationship
      could be found between acne and androgens.

PMID- 1387291
TI  - Expression of vacuolar H(+)-ATPase in mouse osteoclasts during in vitro
      differentiation.
AB  - Osteoclasts express high levels of a vacuolar H(+)-adenosinetriphosphatase (H(+)
      ATPase) on the ruffled membrane which they employ to dissolve bone mineral by
      acidifying their site of attachment on bone. The factors that control
      amplification of H(+)-ATPase during osteoclast differentiation are poorly
      understood. We examined the expression of vacuolar H(+)-ATPase in a cell culture
      system in which mouse spleen cells can be induced to differentiate into
      osteoclasts by coculture with a mouse bone marrow stromal cell line. We found
      that the coculture system produced active osteoclasts, identified as
      multinucleated cells with staining for tartrate-resistant acid phosphatase
      activity that formed genuine resorption pits in bone. These cells developed high
      levels of H(+)-ATPase expression in culture, and omission of dexamethasone or 1
      alpha,25-dihydroxyvitamin D3 from the coculture system each partially suppressed
      the expression of H(+)-ATPase. The results demonstrate that the spleen and PA6
      cell coculture system may be useful for investigating the factors that control
      the induction of H(+)-ATPase amplification that occurs during osteoclast
      differentiation.

PMID- 1387292
TI  - Sliding velocity of isolated rabbit cardiac myosin correlates with isozyme
      distribution.
AB  - To investigate the relationship between the mechanical and biochemical properties
      of cardiac myosin, the sliding velocity of isolated cardiac myosin obtained from
      both euthyroid and hyperthyroid rabbits on actin cables was measured with an in
      vitro motility assay system. Ten rabbits (T) were treated with L-thyroxine to
      induce hyperthyroidism, and eight nontreated animals (N) were used as controls.
      Myosin was purified from the left ventricles of anesthetized animals. Myosin
      isozyme content was analyzed by the pyrophosphate gel electrophoresis method, and
      myosin adenosinetriphosphatase (ATPase) activity was determined on the same
      sample. Long well-organized actin cables of green algae, Nitellopsis, were used
      in the in vitro motility assay. Small latex beads were coated with purified
      cardiac myosin and introduced onto the Nitellopsis actin cables. Active
      unidirectional movement of the beads on the actin cables was observed under a
      photomicroscope, and the velocity was measured. The velocity was dependent on ATP
      concentrations, and the optimal pH for bead movement was approximately 7.0-7.5.
      The mean velocity was higher in T than in N (0.66 +/- 0.12 vs. 0.32 +/- 0.09
      micron/s, P less than 0.01). Both Ca(2+)-activated ATPase activity and the
      percentage of alpha-myosin heavy chain were also higher in T than in N (0.691 +/-
      0.072 vs. 0.335 +/- 0.072 microM Pi.mg-1.min-1, P less than 0.01, and 79 +/- 12
      vs. 26 +/- 7%, P less than 0.01, respectively). The velocity of myosin closely
      correlated with both Ca(+2)-activated myosin ATPase activity (r = 0.87, P less
      than 0.01) and the percentage of alpha-myosin heavy chain (r = 0.87, P less than
      0.01).

PMID- 1387293
TI  - Vasopressin modulates K(+)-channel activities of cultured smooth muscle cells
      from porcine coronary artery.
AB  - The ATP-sensitive K+ channel (KATP channel) and the Ca(2+)-activated K+ channel
      (KCa channel) were active in cell-attached and excised inside-out patch
      configurations in cultured smooth muscle cells of the porcine coronary artery.
      Vasopressin activated the KCa channel (240 pS) when it was applied in the bath in
      the cell-attached patch mode presumably because of an increase in intracellular
      Ca2+, but it had no direct effect on the KCa channel. However, vasopressin
      directly blocked the KATP channel from outside the cell membranes in a
      concentration-dependent manner in both outside-out and cell-attached patch
      configurations; the K(+)-channel opener, nicorandil, reversed this effect. The
      KATP channel (30 pS) was highly active in the intact cell-attached patch
      configuration when the pipette contained a physiological concentration of Ca2+,
      suggesting that this channel may control the resting membrane potential. (The
      block might produce depolarization of the cells and might result in the
      contraction of smooth muscle cells.) These observations suggest that the KATP
      channel may play a role, at least in part, in controlling the contraction of
      smooth muscle cells of the coronary artery and that the control of vascular tone
      by vasopressin may be related to its ability to block the KATP channel.

PMID- 1387294
TI  - Effects of atrial natriuretic peptides on metabolism of arginine vasopressin by
      isolated perfused rat kidney.
AB  - Atrial natriuretic peptide (ANP) antagonizes the release and action of arginine
      vasopressin (AVP) both in vivo and in vitro. We have reported that ANP increases
      the urinary and metabolic clearances of AVP in normal subjects (A. M. Moses et
      al. J. Clin. Endocrinol. Metab. 70: 222-229, 1990). To clarify this effect, we
      perfused isolated rat kidneys in vitro and measured the clearances of AVP for 30
      min after the addition of rat ANP [rANP-(1-28), 10(-7) M]. In the perfused
      kidney, rANP increased the urinary clearance of AVP (UCAVP) from 321 +/- 19 to
      417 +/- 20 microliters/min (P less than 0.01) and increased the glomerular
      filtration rate (GFR) from 558 +/- 28 to 696 +/- 28 microliters/min (P less than
      0.01). Fractional excretion of AVP was unchanged. Rates of AVP reabsorption were
      directly related to filtered AVP, and this relationship was not altered by ANP.
      ANP did not affect the total organ clearance or the renal metabolic clearance of
      AVP. The increase in GFR was associated with increases in renal vascular
      resistance (P less than 0.05), filtration fraction (P less than 0.01), and sodium
      excretion (P less than 0.001). UCAVP also increased when GFR was raised without
      ANP by perfusing at higher pressures. The rat ANP clearance receptor agonist
      [cANP- (4-23), 10(-7) M] did not change GFR or UCAVP. ANP increases UCAVP in the
      isolated perfused rat kidney. This appears to be a hemodynamic effect of ANP,
      acting through its biological receptor and not the clearance receptor.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1387296
TI  - Dexamethasone stimulates release of an ANP-like substance from rainbow trout
      cardiocytes.
AB  - A substance that cross-reacts with antiserum to human atrial natriuretic peptide
      (ANP) is found in fish hearts. This ANP-like material increases sodium output
      from the gill and kidney while inhibiting sodium uptake in the gut. Mammalian ANP
      secretion is stimulated by glucocorticoids, and cortisol injection increases
      sodium output in salt-loaded fish. Therefore, we wanted to determine if the
      release of ANP in fish is sensitive to dexamethasone. Ventricle cardiocytes from
      the rainbow trout Oncorhynchus mykiss were treated with various doses of
      dexamethasone for 18 or 72 h. Single ventricle cells were then assayed for ANP
      release using a reverse hemolytic plaque assay and antiserum to human alpha-ANP.
      Incubation with 100 microM dexamethasone almost doubled the population of
      ventricle cells committed to ANP release (basal, 15.0 +/- 0.3% vs. Dexamethasone,
      28.3 +/- 1.4%; values are percent plaque formation +/- SE). Stimulation of ANP
      secretion was dependent on dose and time of exposure to dexamethasone. These
      results suggest that ANP secretion in fish is regulated by glucocorticoids.

PMID- 1387295
TI  - Rat brain natriuretic peptide is localized in atrial granules and released into
      the circulation.
AB  - Rat brain natriuretic peptide (BNP) was detected by radioimmunoassay in heart
      atria and ventricles and in plasma. We have investigated its localization in
      atria and the possibility of cosecretion of atrial natriuretic factor (ANF) and
      BNP into the circulation. BNP was detected by chromatographic analysis and
      immunoblotting in the isolated atrial granules together with ANF: It consisted of
      two immunoreactive proteins of 14,000 and 2,500 apparent molecular weight. By
      immunohistochemical methods, BNP was particularly found in the perinuclear region
      of atrial cardiocytes. Double-labeling immunocytochemical methods colocalized BNP
      and ANF in the same atrial secretory granules. Basal plasma BNP levels ranged
      from 2.6 to 4.4 fmol/ml. After stimuli by morphine injection or an aortocaval
      shunt, BNP levels increased by 4- and 7-fold, respectively, whereas ANF levels
      rose by 50- and 6-fold, respectively. Depending on the stimulus, BNP release into
      the circulation is not necessarily proportional to ANF, indicating that BNP may
      originate not only from the atrial granules but also from other tissues such as
      the ventricles. These results suggest that BNP may participate with ANF in blood
      pressure control and salt and water homeostasis.

PMID- 1387297
TI  - Pulmonary function and stress response after laparoscopic cholecystectomy:
      comparison with subcostal incision and influence of thoracic epidural analgesia.
AB  - Laparoscopic cholecystectomy (LPC) is increasingly used to treat symptomatic
      cholelithiasis. We compared the effects of cholecystectomy by subcostal incision
      to those of LPC on lung function and endocrine metabolic response. The effects of
      thoracic epidural analgesia for LPC were studied as well. Thirty patients
      undergoing elective cholecystectomy under general anesthesia were allocated to
      three study groups: group I, cholecystectomy by subcostal incision; group II,
      LPC; group III, LPC and epidural analgesia with 0.5% bupivacaine with
      epinephrine, followed by continuous epidural infusion of 6 mL of 0.5%
      bupivacaine. Forced vital capacity (FVC), peak expiratory flow, and forced
      expiratory volume in 1 s were measured with the patients in a half-sitting
      position. In all groups, sustained decreases in FVC, forced expiratory volume in
      1 s, and peak expiratory flow were observed up to 24 h after surgery. Reduction
      of FVC was significantly more in group I compared with groups II and III (P less
      than 0.05). The FVC in group I decreased from 3.8 +/- 0.42 (SD) to 1.1 +/- 0.27 L
      (P less than 0.01), in group II from 3.6 +/- 1.46 to 2.1 +/- 0.94 L (P less than
      0.05), and in group III from 3.8 +/- 0.92 to 2.8 +/- 0.90 L (P less than 0.05).
      In all groups, plasma glucose and cortisol increased after surgery compared with
      baseline levels (P less than 0.05). At 240 min after surgery, a small but
      significant decrease of cortisol was measured in group III (P less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387298
TI  - Histochemical and immunohistochemical study of the mucosal lymphoid system in
      swine.
AB  - Enzyme histochemical and immunohistochemical techniques were used to examine
      palatine tonsils and aggregated lymphoid follicles (Peyer's patches) of the ileum
      in 6- to 9-day-old and in 6-month-old pigs. Histochemical techniques were used to
      detect alpha-naphthyl-acetate esterase (ANAE), alpha-naphthyl-butyrate esterase
      (ANBE), beta-glucuronidase, adenosine triphosphatase (ATPase), and acid
      phosphatase (AcP). Nonspecific esterases (ANAE, ANBE) were detected in
      macrophages, T-cell area lymphocytes, eosinophils, fibroblastic reticular cells
      (FRC), follicular dendritic cells (FDC), and interdigitating cells (IDC). beta
      Glucuronidase reactivity was strong in macrophages, eosinophils, FDC, and IDC,
      and weaker in FRC. Adenosine triphosphatase reactivity was detected in B-cell
      area lymphocytes, FDC, FRC, and IDC. Cell types with acid phosphatase reactivity
      were macrophages, FDC, FRC, and IDC. Nonepithelial cells of tonsils and
      aggregated lymphoid follicles of the ileum had similar enzymatic reactions. In
      Peyer's patches, however, epithelial cells were positive for all enzymes studied;
      in tonsils, only nonspecific esterases were detected. Immunoperoxidase techniques
      were used to detect S-100 protein and cytoplasmic immunoglobulins (IgG, IgM, and
      IgA). The S-100 protein was detected in lymphocytes, FDC, and FRC of tonsils and
      Peyer's patches; in tonsillar epithelial and endothelial cells; and in IDC of
      Peyer's patches.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387299
TI  - Characterization and pathogenicity for pigs of a hog cholera virus strain
      isolated from wild boars.
AB  - One hog cholera virus strain isolated from an outbreak of the disease in a wild
      boar breeding herd in Brittany (France) in 1990 has been characterized with a
      panel of monoclonal antibodies to hog cholera virus and ruminant pestiviruses:
      the strain was found to be indistinguishable from that of other domestic pig
      isolates. The pathogenicity of the strain to domestic pigs was evaluated by
      infecting intranasally, intramuscularly and by contact 17 specific pathogen-free
      6-week- and 12-week-old pigs. Sixteen of the 17 pigs showed symptoms of hog
      cholera. The virus was detected in the blood of the 16 pigs during all phases of
      hyperthermia which persisted up to death or the terminal phase, ie between 16 and
      29 days post-infection. One animal recovered after presenting a mild form of the
      disease. This pig was the only one which raised antibodies to the virus. Typical
      hog cholera lesions were observed in 2 pigs only; the other animal showed very
      few pathological changes. No relationship between intensity or duration of the
      disease and pathological changes could be established.

PMID- 1387300
TI  - Serological alpha 1-antichymotrypsin in Down's syndrome and Alzheimer's disease.
AB  - alpha 1-Antichymotrypsin (ACT) is a serine protease inhibitor that is markedly
      elevated in the serum and cerebrospinal fluid of patients with Alzheimer's
      disease (AD). Patients with Down's syndrome are known to develop
      neuropathological changes of AD by age 40 years and many become demented.
      Therefore, in the present study, we obtained serum ACT levels from patients with
      Down's syndrome and AD, diagnosed by autopsy or clinically, and healthy control
      subjects. Newman-Keuls' multiple range test revealed a significantly greater (p
      less than 0.01) mean ACT level in the Autopsy AD (906.4 +/- 94.64 mg/L) and
      Clinical AD (745.00 +/- 59.95 mg/L) groups in contrast to the Old Control group
      (531.00 +/- 23.05 mg/L). The mean ACT level of the Down's Syndrome group (513.33
      +/- 14.73 mg/L) was not significantly different from that of the Young Control
      subjects. Furthermore, we did not observe a positive correlation of ACT levels
      with age in the Down's Syndrome group, in spite of the age-dependent premature
      increase in neuropathological changes of AD that are known to occur in patients
      with Down's syndrome. A positive correlation between serum ACT levels and the
      density of plaques or tangles, neuropathological hallmarks of AD, in brains of
      patients with AD also did not exist. Thus, our results suggest that ACT levels
      may not parallel the development of the classical neuropathological hallmarks of
      AD.

PMID- 1387301
TI  - Absolute bioavailability of clarithromycin after oral administration in humans.
AB  - The absolute bioavailability of clarithromycin, a new macrolide antimicrobial
      agent, was assessed in a three-way, randomized, single-dose, crossover study
      conducted with 22 healthy volunteers, 19 of whom provided analyzable study data.
      The bioavailability parameters of two 250-mg oral tablet formulations were
      calculated with reference to an identical dose administered by intravenous
      infusion of the lactobionate salt. After adjustment for formulation potency, the
      mean absolute bioavailabilities of the two oral formulations were 52 and 55%, on
      the basis of the appearance of parent compound in the systemic circulation.
      Metabolite peak concentration and area under the plasma concentration-time curve
      data after oral dosing were generally greater than those after intravenous
      infusion, suggesting that marked first-pass metabolism of clarithromycin occurs
      after oral administration. Pharmacokinetic analysis of the parent drug and the
      active 14-hydroxy metabolite data suggests complete (or nearly complete)
      absorption of the drug after oral administration.

PMID- 1387302
TI  - Comparison of the intracellular activities of clarithromycin and erythromycin
      against Mycobacterium avium complex strains in J774 cells and in alveolar
      macrophages from human immunodeficiency virus type 1-infected individuals.
AB  - The intracellular activities of clarithromycin and erythromycin, alone and in
      combination with other antimicrobial agents, were tested against Mycobacterium
      avium complex (MAC) strains inside mouse J774 cells and inside alveolar
      macrophages obtained from human immunodeficiency type 1-infected individuals.
      Clarithromycin alone had greater intracellular activity than erythromycin alone,
      and drug combinations that included clarithromycin were usually more active than
      combinations that included erythromycin.

PMID- 1387304
TI  - Replacement of the valvular prosthesis in a patient with a Bentall procedure.
AB  - Patients who have had the Bentall-DeBono procedure using a composite conduit with
      a tissue valvular prosthesis pose a great challenge when problems develop with
      the tissue prosthesis. We herein report the surgical management of one such case,
      in which the valvular prosthesis was removed and replaced without replacement of
      the conduit.

PMID- 1387305
TI  - Balloon angioplasty in the treatment of aortic coarctation.

PMID- 1387303
TI  - Clarithromycin-ciprofloxacin-amikacin for therapy of Mycobacterium avium
      Mycobacterium intracellulare bacteremia in patients with AIDS.
AB  - A combination of clarithromycin, ciprofloxacin, and amikacin for the treatment of
      Mycobacterium avium-Mycobacterium intracellulare bacteremia was evaluated in 12
      AIDS patients. Mycobacteremia cleared in all patients by 2 to 8 weeks of
      treatment, and symptoms resolved. Four patients died; all had negative blood
      cultures until death, and disseminated M. avium-M. intracellulare complex
      infection was not considered the primary cause of death.

PMID- 1387306
TI  - Siderophore and organic acid production in root nodule bacteria.
AB  - Nineteen strains of root nodule bacteria were grown under various iron regimes
      (0.1, 1.0 and 20 microM added iron) and tested for catechol and hydroxamate
      siderophore production and the excretion of malate and citrate. The growth
      response of the strains to iron differed markedly. For 12 strains (Bradyrhizobium
      strains NC92B and 32H1, B. japonicum USDA110 and CB1809, B. lupini WU8, cowpea
      Rhizobium NGR234, Rhizobium meliloti strains U45 and CC169, Rhizobium
      leguminosarum bv viciae WU235 and Rhizobium leguminosarum bv trifolii strains
      TA1, T1 and WU95) the mean generation time showed no variation with the 200-fold
      increase in iron concentration. In contrast, in Bradyrhizobium strains NC921,
      CB756 and TAL1000, B. japonicum strain 61A76 and R. leguminosarum bv viciae
      MNF300 there was a 2-5 fold decrease in growth rate at low iron. R. meliloti
      strains WSM419 and WSM540 showed decreased growth at high iron. All strains of
      root nodule bacteria tested gave a positive CAS (chrome azurol S) assay for
      siderophore production. No catechol-type siderophores were found in any strain,
      and only R. leguminosarum bv trifolii T1 and bv viciae WU235 produced hydroxamate
      under low iron (0.1 and 1.0 microM added iron). Malate was excreted by all
      strains grown under all iron regimes. Citrate was excreted by B. japonicum
      USDA110 and B. lupini WU8 in all iron concentrations, while Bradyrhizobium
      TAL1000, R. leguminosarum bv viciae MNF300 and B. japonicum 61A76 only produced
      citrate under low iron (0.1 and/or 1.0 microM added iron) during the stationary
      phase of growth.

PMID- 1387307
TI  - Mesulergine induced Leydig cell tumours, a syndrome involving the pituitary
      testicular axis of the rat.

PMID- 1387308
TI  - The cell cycle regulator, human p50weel, is a tyrosine kinase and not a
      serine/tyrosine kinase.
AB  - The human weel protein, a homologue of the yeast weel protein, was expressed in
      E. coli and purified to homogeneity. The purified weel protein phosphorylated the
      tyrosine residue of cdc2 kinase in HeLa cell extracts in the presence of human
      cyclin B1. It also phosphorylated the tyrosine but not the threonine residue in
      the peptide of the amino-terminal of cdc2 kinase, although both these residues
      have been shown to be phosphorylated in higher eukaryotes in vivo. Furthermore,
      serine and tyrosine residues of the yeast weel protein are reportedly
      autophosphorylated in vitro, however the tyrosine residue of the human weel
      protein was autophosphorylated whereas the serine and threonine residues were
      not. These data indicate that human p50weel is tyrosine kinase and that it
      phosphorylated the tyrosine residue of the amino-terminal of cdc2 kinase in the
      presence of cyclin B1 and that the threonine residue is phosphorylated by
      another, unknown kinase.

PMID- 1387309
TI  - Internalization of V2-vasopressin receptors in LLC-PK1-cells: evidence for
      receptor-mediated endocytosis.
AB  - The mechanism of internalization of the vasopressin-receptor (V2-subtype) of LLC
      PK1-cells, a pig renal tubular cell line, is unknown. We studied internalization
      utilizing a novel, highly specific vasopressin analogue ((125I)-[8-p(OH)
      phenylpropionyl]-LVP, 2000 Ci/mmol). Scatchard analysis performed with membranes
      of LLC-PK1-cells revealed a Kd of 0.8 +/- 0.2 nM and a Bmax of 366 +/- 41 fmol/mg
      of protein. Degradation of the ligand was excluded by RP-HPLC-analysis.
      Internalization was proven by the acid-wash technique, quantitative light
      microscopic autoradiography and electron microscopy. The ligand was internalized
      in a time- and temperature-dependent manner. At 4 degrees C, no uptake was found;
      at 22 degrees C, after 30 min of incubation, more than 50% of the radioligand was
      found inside the cell. Electron microscopy demonstrated that plasma-membrane
      bound vasopressin receptors are internalized by receptor-mediated endocytosis via
      coated pits.

PMID- 1387310
TI  - Regulatory role of GM3 ganglioside in integrin function, as evidenced by its
      effect on function of alpha 5 beta 1-liposomes: a preliminary note.
AB  - Mouse mammary carcinoma mutant cell line FUA169, characterized by high GM3
      ganglioside content, was established from parent cell line FM3A/F28-7, which has
      high LacCer content but no GM3. Although both cell lines showed the same quantity
      and quality of integrin receptors, FUA169 showed much stronger adhesion to
      fibronectin (FN)-coated plates than did F28-7. Liposomes containing
      phosphatidylcholine, cholesterol, alpha 5 beta 1, and a moderate amount of GM3
      showed greatly enhanced adhesion to FN-coated plates, but adhesion of similar
      liposomes containing a large amount of GM3, or no GM3, was much lower. Our
      results suggest that GM3 regulates integrin receptor function essential for cell
      adhesion to FN.

PMID- 1387311
TI  - Electrophoretic profiles of mitochondrial plasmids in Neurospora suggest they
      replicate by a rolling circle mechanism.
AB  - Migratory behaviour of mitochondrial plasmids from Neurospora crassa Mauriceville
      1c and N. intermediate LaBelle has been studied by pulsed field gel
      electrophoresis (PFGE). Electrophoretic profiles demonstrate that long, linear
      molecules of a heterogeneous size are the prevailing form of plasmid DNA in vivo.
      Circular forms represent less than 8-9% of plasmid DNA. Single stranded DNA
      regions are abundant and lead to electrophoretic inertia of a significant amount
      of plasmid DNA. These profiles indicate that both plasmids replicate by the
      recombination dependent rolling circle mechanism.

PMID- 1387312
TI  - Binding characteristics of the new thromboxane A2/prostaglandin H2 receptor
      antagonist [3H]BAY U 3405 to washed human platelets and platelet membranes.
AB  - The new thromboxane A2 antagonist [3H]BAY U 3405 was characterized for its
      binding to washed human platelets and platelet membranes. In washed platelets the
      specific binding was reversible, selective and stereospecific, but not saturable.
      The dissociation constant (Kd) was 6 +/- 2.5 nM, the number of specific binding
      sites 1177 +/- 306 per platelet. Three structurally different thromboxane A2
      (TXA2)/prostaglandin H2 (prostaglandin endoperoxide) (PGH2) receptor ligands
      completely inhibited the specific binding of [3H]BAY U 3405 in a concentration
      dependent manner, indicating that the observed high affinity binding site is the
      TXA2/PGH2 receptor. In platelet membranes, however, specific [3H]BAY U 3405
      binding showed saturability in addition to reversibility, selectivity, and
      stereospecifity. The Kd of the binding was 9.6 +/- 2.3 nM in kinetic studies and
      8.7 +/- 3.7 nM in saturation studies, the inhibition constant (Ki) was 10 +/- 1.1
      nM in displacement studies. The TXA2/PGH2 receptor agonists U 46619 and CTA2, and
      the antagonists Daltroban (BM 13505), I-PTA-OH and SQ 29548 all completely
      inhibited the specific binding of [3H]BAY U 3405 thus defining the observed
      binding site as the TXA2/PGH2 receptor. In conclusion, the data suggest that the
      previously reported TXA2 antagonism of BAY U 3405 is mediated by binding to a
      specific high affinity binding site of human platelets and platelet membranes
      that represents the TXA2/PGH2 receptor.

PMID- 1387313
TI  - Antiflammins. Anti-inflammatory activity and effect on human phospholipase A2.
AB  - Two anti-inflammatory peptides (antiflammins) corresponding to a high amino acid
      similarity region between lipocortin I and uteroglobin were tested for their
      ability to inhibit purified human synovial fluid phospholipase A2 (HSF-PLA2). No
      inhibitory activity was observed, even at such high concentrations of peptides as
      50 microM. When antiflammins were preincubated with the enzyme and/or the
      substrate, no HSF-PLA2 inhibition was detected. In vivo anti-inflammatory
      activity of these peptides was evaluated in several experimental models of
      inflammation induced by carrageenan, croton-oil, oxazolone and Naja naja naja
      venom phospholipase A2 (PLA2). In contrast to the in vitro results, anti
      inflammatory activity was observed in all tests, except when inflammation was
      induced by snake venom PLA2. Taken together, our results do not support the
      hypothesis that the in vivo anti-inflammatory effect of antiflammins is directly
      related to inhibition of PLA2 activity.

PMID- 1387314
TI  - Metabolism of NAD(P)H by blood components. Relevance to bioreductively activated
      prodrugs in a targeted enzyme therapy system.
AB  - NADH was metabolized both by serum components and at the cell surface. The
      metabolism by serum was either oxidation to NAD+, or hydrolysis of the
      pyrophosphate to yield nicotinamide mononucleotide (reduced) (NMNH) and AMP. NMNH
      was further hydrolysed to yield nicotinamide riboside (reduced) (NRH), which was
      stable. NAD+ was hydrolysed (although at a slower rate than was NADH), but was
      also reduced to yield NADH. The reduction of NAD+ was catalysed by the enzyme
      serum L(+)lactate dehydrogenase (EC 1.1.1.27) and was dependent on the
      concentration of L(+)lactate in the serum. NADPH was hydrolysed in a similar
      manner to NADH but not oxidized by serum. NADH generated from NAD+ by serum
      derived from human, foetal calf and horse sources was capable of driving the
      bioreductive activation of CB 1954 by the enzyme DT diaphorase. Cell surfaces
      oxidized NADH to NAD+, but did not oxidize NADPH or NRH. These observations
      suggest that NAD(P)H would be unsuitable as a source of reducing equivalents for
      the bioreductive activation of prodrugs by a reductase enzyme in Antibody
      Directed Enzyme Prodrug Therapy (ADEPT). In contrast, NAD+ (which could act as a
      source of NADH) and NRH could avoid the shortcomings of NAD(P)H, and act as
      suitable cofactors for an enzyme in an ADEPT system.

PMID- 1387315
TI  - Regulation of inflammation by lipocortin 1.
AB  - The mechanisms that regulate inflammatory responses, and their dysfunction in
      chronic inflammatory diseases, are poorly understood. Lipocortin 1 is a potential
      mediator of the anti-inflammatory effects of glucocorticoid hormones. Following
      the discovery of putative receptors on phagocytes for lipocortin 1, Nick Goulding
      and Paul Guyre here offer one explanation for the self-limitation of inflammation
      and the impairment of the mechanism in chronic inflammatory disease.

PMID- 1387316
TI  - Is there a role for gamma delta T cells in malaria?
AB  - Peripheral blood lymphocytes of the V gamma 9+ family of gamma delta T cells
      proliferate vigorously in response to Plasmodium falciparum. In this brief
      article, Jean Langhorne and colleagues discuss this response and assess the
      possible role of gamma delta T cells in the pathogenesis of malaria.

PMID- 1387317
TI  - Effect of heart rate on centerline velocities of pulsatile intracardiac jets: an
      in vitro study with laser Doppler anemometry and pulsed Doppler ultrasound.
AB  - This article confirms a recently developed distal jet centerline technique for
      noninvasively quantifying regurgitant cardiac valve flows. The basic principle
      that allows flow rate to be calculated is conservation of momentum. As the jet
      entrains more mass, its centerline velocity decays inversely with distance from
      the orifice. Under pulsatile flow conditions, it has been shown that this
      technique remains applicable at peak flow for a normal resting adult heart rate
      of 60 to 70 beats/min. It is, however, conceivable that at higher heart rates,
      the same inverse relation between centerline velocity and distance is never fully
      established, because there is a finite time interval required for the jet to
      penetrate the receiving chamber. Therefore, the purpose of this study was to
      determine whether the inverse relationship of centerline velocity to distance
      develops sufficiently rapidly so that quantitative techniques based on that decay
      would be applicable over a wide range of heart rates. Two different techniques,
      an engineering tool, laser Doppler anemometry, and a clinical tool, Doppler
      ultrasound, were used for measuring jet centerline velocities (averaged over
      multiple beats). Physiologic pulsatile flows were pumped through two circular
      orifices, 4 and 6 mm in diameter, at 60 to 150 beats/min; peak orifice velocities
      ranged from 2 to 5 m/sec. Steady flow experiments were also performed with the
      same orifice diameters and over the same velocity range. Peak centerline
      velocities in the fully developed turbulent jet region decayed inversely with
      distance at all heart rates studied. With laser Doppler anemometry, the
      proportionality constant of the decay curve was found to be in the range 6.4 +/-
      0.5. The pulsed Doppler results provided a jet constant in the range 6.7 +/- 0.3
      with the 4-mm orifice diameter, whereas the constant was 6.5 +/- 0.3 with the 6
      mm orifice diameter. In steady flow, the proportionality constant was found to be
      6.1 +/- 0.2. Therefore, within a wide range of physiologic heart rates, full jet
      development occurs with sufficient speed so that the expected centerline velocity
      decay is established (jet empirical constant of 6.3). The conservation of
      momentum technique for calculating orifice flow rate on the basis of these
      centerline velocities is thus applicable under physiologic conditions.

PMID- 1387318
TI  - The effects on toxicity of circadian patterning of continuous hepatic artery
      infusion.
AB  - Long term continuous hepatic artery infusion of FUDR was carried out in 34 rats.
      In the animals who received a constant infusion schedule of 15 mg/kg/day all died
      of toxicity with a mean survival of 9.3 days. If the pattern of the continuous
      infusion was changed so that over 60% of the infusion was given during the hours
      of 3pm to 9pm than all of the animals survived the 14 day infusion. If the
      maximum dose of infusion was changed so that 60% of the infusion was given at
      night from 3am to 9am the infusion became more toxic and all the animals died in
      a mean of 5.5 days. Pathologic sectioning of all the livers reflected the above
      outcomes with the greatest amount of hepatic necrosis in the animals on the night
      cycles. This study underscores the recent advances in chronobiology demonstrating
      that for continuous hepatic arterial infusions the timing of delivery is crucial
      in determining the toxicity.

PMID- 1387319
TI  - 18O isotopic 13C NMR shift as proof that bifunctional peptidylglycine alpha
      amidating enzyme is a monooxygenase.
AB  - The biosynthesis of C-terminal alpha-amidated peptides from their corresponding C
      terminal glycine-extended precursors is catalyzed by peptidylglycine alpha
      amidating enzyme (alpha-AE) in a reaction that requires copper, ascorbate, and
      molecular oxygen. Using bifunctional type A rat alpha-AE, we have shown that O2
      is the source of the alpha-carbonyl oxygen of pyruvate produced during the
      amidation of dansyl-Tyr-Val-[alpha-13C]-D-Ala, as demonstrated by the 18O
      isotopic shift in the 13C NMR spectrum of [alpha-13C]lactate generated from
      [alpha-13C]pyruvate in the presence of lactate dehydrogenase and NADH. In
      addition, one-to-one stoichiometries have been determined for glyoxylate
      formed/dansyl-Tyr-Val-Gly consumed, pyruvate formed/dansyl-Tyr-Val-D-Ala
      consumed, dansyl-Tyr-Val-NH2 formed/ascorbate oxidized, and dansyl-Tyr-Val-NH2
      formed/O2 consumed. Quantitative coupling of NADH oxidation to dansyl-Tyr-Val-NH2
      production using Neurospora crassa semidehydroascorbate reductase showed that two
      one-electron reductions by ascorbate occurred per alpha-AE turnover. The
      stoichiometry of approximately 1.0 dansyl-Tyr-Val-NH2 produced/ascorbate oxidized
      observed in the absence of a semidehydroascorbate trap resulted from the
      disproportionation of two semidehydroascorbate molecules to ascorbate and
      dehydroascorbate.

PMID- 1387320
TI  - Dynamic conformations compared for IgE and IgG1 in solution and bound to
      receptors.
AB  - Dynamic conformations of two distinct immunoglobulin (Ig) isotypes, murine IgE
      and human IgG1, were examined with fluorescence resonance energy transfer
      measurements. The IgE mutant epsilon/C gamma 3* and the IgG1 mutant gamma/C gamma
      3* each bind [5-(dimethylamino)naphthalen-1-yl]sulfonyl (DNS) in two identical
      antigen binding sites at the amino (N)-terminal ends of the Ig in the Fab
      segments. Eosin-DNS bound in these Fab sites served as the acceptor probe in
      these studies. Both Ig have a carboxy (C)-terminal domain (C gamma 3*) which
      contains genetically introduced cysteine residues. Modification of these cysteine
      sulfhydryls with fluorescein maleimide provided donor probes near the C-terminal
      ends of the Ig in the Fc segment. Energy transfer between the C-terminal and N
      terminal ends was compared for these two Ig in solution and when they were found
      to their respective high-affinity receptors on plasma membranes: IgE-Fc epsilon
      RI on RBL cell membranes and IgG1-Fc gamma RI on U937 cell membranes. Previous
      energy-transfer measurements with these probes yielded an average end-to-end
      distance of 71 A for IgE in solution and 69 A for IgE bound to Fc epsilon RI,
      indicating that in both situations IgE is bent such that the axes of the Fab
      segments and the axis of the Fc segment do not form a planar Y-shape [Zheng,
      Shopes, Holowka, & Baird (1991) Biochemistry 30, 9125]. In the current study we
      found the average end-to-end distance for IgG1 in solution is 75 A and greater
      than or equal to 85 A for IgG1 bound to Fc gamma RI, suggesting an average bend
      conformation for IgG1 as well. The contributions of segmental flexibility to the
      average distances were assessed directly by measuring the efficiency of energy
      transfer as a function of variations in donor quantum yield caused by a
      collisional quencher and using these data to extract a Gaussian distribution of
      end-to-end distances. The distribution average (rho) and half-width (hw) were
      determined to be as follows: rho = 75 A, hw = 24 A for IgE in solution; rho = 71
      A, hw = 12 A for IgE bound to Fc epsilon RI; and rho = 100 A, hw = 88 A for IgG
      in solution.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1387321
TI  - Roles of Mg2+ in the mechanism of formation and dissociation of open complexes
      between Escherichia coli RNA polymerase and the lambda PR promoter: kinetic
      evidence for a second open complex requiring Mg2+.
AB  - Comparative studies of the effects of Mg2+ vs Na+ and of acetate (OAc-) vs Cl- on
      the kinetics of formation and dissociation of E. coli RNA polymerase (E sigma 70)
      lambda PR promoter open complexes have been used to probe the mechanism of this
      interaction. Composite second-order association rate constants ka and first-order
      dissociation rate constants kd, and their power dependences on salt concentration
      SKa (SKa identical to d log ka/d log [salt]) and Skd (Skd identical to d log kd/d
      log [salt]), were determined in MgCl2 and NaOAc to compare with the results of
      Roe and Record (1985) in NaCl. Replacement of NaCl by MgCl2 reduces the magnitude
      of Ska 2-fold (Ska = -11.9 +/- 1.1 in NaCl; Ska = -5.2 +/- 0.3 in MgCl2) and (by
      extrapolation) drastically reduces the magnitude of ka at any specified salt
      concentration (e.g., approximately 10(6)-fold at 0.2 M). Replacement of NaCl by
      NaOAc does not significantly affect Ska (Ska = -12.0 +/- 0.7 in NaOAc) and (by
      extrapolation) increased ka by approximately 80-fold at any fixed [Na+]. In the
      absence of Mg2+, replacement of NaCl by NaOAc is found to increase the half-life
      of the open complex by approximately 560-fold at fixed [Na+] without affecting
      Skd [Skd = 7.6 +/- 0.1 in NaOAc; in NaCl, Skd = 7.7 +/- 0.2 (Roe & Record,
      1985)]. Replacement of NaCl by MgCl2 drastically reduces both Skd and the half
      life of the open complex at any salt concentration below approximately 0.2 M.
      Strikingly, Skd = 0.4 +/- 0.1 in MgCl2, indicating that the net uptake of Mg2+
      ions in the kinetically significant steps in dissociation of the open complex is
      much smaller than that expected by analogy with the uptake of approximately 8 Na+
      ions in the corresponding steps in NaCl. In NaCl/MgCl2 mixtures, at a constant
      [NaCl] in the range 0.1-0.2 M, initial addition of MgCl2 (0.5 mM less than or
      equal to [MgCl2] less than or equal to 1 mM) increases the half-life of the open
      complex; further addition of MgCl2 causes the half-life to decrease, though the
      effect of [MgCl2] on kd is always less than that predicted by a simple
      competitive model. The observed effects of MgCl2 on Skd and kd differ profoundly
      from those expected from the behavior of kd and Skd in NaCl and NaOAc and
      indicate that the role of Mg2+ in dissociation is not merely that of a
      nonspecific divalent competitor with RNAP for interactions with DNA phosphates
      and of a DNA helix-stabilizer, both of which should cause kd to increase
      monotonically with increasing [Mg2+].(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1387322
TI  - Two-dimensional NMR, circular dichroism, and fluorescence studies of PP-50, a
      synthetic ATP-binding peptide from the beta-subunit of mitochondrial ATP
      synthase.
AB  - PP-50, a peptide based on residues 141-190 of the beta-subunit of mitochondrial
      F1-ATPase, contains the GX4GKT consensus region for nucleoside triphosphate
      binding and has been shown to bind ATP [Garboczi, D.N., Shenbagamurthi, W.K.,
      Hullihen, J., & Pedersen, P.L. (1988) J. Biol. Chem. 263, 812-816]. At pH 4.0,
      appropriate for NMR studies, PP-50 retains the ability to bind ATP tightly (KD =
      17.5 microM) with a 1:1 stoichiometry as shown by titrations measuring the
      partial quenching of ATP fluorescence by PP-50. CD spectra of PP-50 at pH 4.0 and
      at low ionic strength show 5.8% helix, 30.2% beta-structure, and 64% coil. ATP
      binding increases the structure of PP-50, changing the CD to 7.5% helix, 44.5%
      beta-structure, and 48% coil. Increasing the ionic strength to 50 mM KCl also
      increases the structure, changing the CD to 7.4% helix, 64.4% beta-structure, and
      28.2% coil. The 600-MHz proton NMR spectrum of PP-50, at pH 4.0 and low ionic
      strength, has been assigned by 2D methods (TOCSY, DQF-COSY, and NOESY with jump
      return water suppression). Based on strong d alpha N NOEs, J alpha N values, and
      NH chemical shifts differing from random coil values, regions of extended
      structure are detected from residues 1-7 and 43-48. Based on dNN, dNN(i,i+2), and
      d alpha N(i,i+2) NOEs and 3J alpha N values, possible type I' and type I turns
      are found from residues 11-14 and 31-34, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1387323
TI  - Early steps of the Mg(2+)-ATPase of relaxed myofibrils. A comparison with Ca(2+)
      activated myofibrils and myosin subfragment 1.
AB  - The early steps of the Mg(2+)-ATPase activity of relaxed rabbit psoas myofibrils
      were studied in a buffer of near-physiological ionic strength at 4 degrees C by
      the rapid flow quench technique. The initial ATP binding steps were studied by
      the ATP chase, and the cleavage and release of product steps by the Pi burst
      method. The data obtained were interpreted by [formula: see text] where M
      represents the myosin heads with or without actin interaction. This work is a
      continuation of our study on Ca(2+)-activated myofibrils [Houadjeto, M., Travers,
      F., & Barman, T. (1992) Biochemistry 31, 1564-1569]. Here the constants obtained
      with relaxed myofibrils were compared with those with activated myofibrils and
      myosin subfragment 1 (S1). We find that whereas Ca2+ increases 80X the release of
      products (k4), it has little effect upon the kinetics of the initial binding and
      cleavage steps. As with activated myofibrils and S1, the second-order binding
      constant for ATP (k2/K1) was about 1 microM-1 s-1 and the ATP was bound very
      tightly. With activated myofibrils, it was difficult to obtain an estimate for
      the koff for ATP(k-2) but it is much less than kcat. Here with relaxed myofibrils
      we estimate k-2 less than 8 x 10(-4) s-1, which is considerably smaller than kcat
      (0.019 s-1) and also previous estimates for this constant. The overall Kd for ATP
      to relaxed myofibrils is less than 8 x 10(-10) M. With S1 this Kd is about 10(
      11) M.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387324
TI  - Gestational hyperlipidemia in the rat is characterized by accumulation of n - 6
      and n - 3 fatty acids, especially docosahexaenoic acid.
AB  - We have evaluated the relative and quantitative changes in long-chain fatty acids
      in maternal liver, serum, carcass and conceptus (fetuses plus placentae) during
      pregnancy in the rat, to ascertain whether previous concern over lower
      proportions of n - 6 and n - 3 fatty acids in maternal serum could be indicative
      of suboptimal n - 6 or n - 3 fatty acid status. Gestational hyperlipidemia was
      characterized by proportional decreases in linoleic, stearic and arachidonic
      acids but increases in palmitic and docosahexaenoic acids. However, the
      quantitative amount (microgram/ml) of linoleic, arachidonic and docosahexaenoic
      acids in serum lipids actually increased 2-5-fold from mid-pregnancy to term.
      Compared to non-pregnant rats, gestational hyperlipidemia was also associated
      with a lower proportion but similar quantity of linoleic acid in maternal carcass
      and adipose stores. We conclude that gestational hyperlipidemia in the rat is
      characterized by a relative but not quantitative decrease in whole-body stores of
      n - 6 fatty acids and a marked proportional and quantitative increase in
      docosahexaenoic acid in maternal organs and in the conceptus.

PMID- 1387326
TI  - Primary structure of V-ATPase subunit B from Manduca sexta midgut.
AB  - The amino acid sequence of a vacuolar-type ATPase (V-ATPase) subunit B has been
      deduced from a cDNA clone isolated from a Manduca sexta larval midgut library.
      The library was screened by hybridization with a labeled cDNA encoding subunit B
      of Arabidopsis thaliana tonoplast V-ATPase. The M. sexta V-ATPase subunit B
      consists of 494 amino acids with a calculated M(r) of 54,902. The amino acid
      sequence deduced for V-ATPase subunit B of M. sexta is between 98% and 76%
      identical with that of seven other V-ATPase subunits B and greater than 52%
      identical with three archaebacterial ATPase subunits B.

PMID- 1387327
TI  - Antiemetic agents.
AB  - Despite major progress in the treatment of chemotherapy-induced emesis, nearly
      one third of patients undergoing cisplatin-based regimens still experience emesis
      within the first 24 hours of chemotherapy. An adequate treatment of delayed and
      anticipatory emesis remains to be determined. For highly emetogenic chemotherapy,
      the combination of ondansetron and dexamethasone is superior to dexamethasone
      alone and protects most patients. For moderately emetogenic regimens, the high
      level of complete control that can be achieved with the use of standard
      antiemetics is comparable to that obtained with ondansetron. This would suggest
      that, to reduce the cost of antiemetic therapy, ondansetron can be limited in
      case of failure of standard therapy. Delayed emesis remains poorly controlled
      with no difference between metoclopramide, dexamethasone, ondansetron, and
      placebo. Although some data suggest an improved efficacy when combining
      ondansetron with dexamethasone, convincing confirmatory studies are needed.

PMID- 1387325
TI  - Limitations of phosphatidylcholine/deoxycholate mixtures for the analysis of
      phospholipase A2 inhibition and activation: illustration with annexins.
AB  - The effects of human recombinant lipocortin I (annexin I) and bovine lung
      calpactin I (annexin II) on porcine pancreatic phospholipase A2 (PLA2) activity
      in phosphatidylcholine (PC)/deoxycholate (DOC) mixtures were investigated.
      Annexin-associated decreases in PLA2 activity were observed under some
      conditions, for example, at high DOC/PC molar ratios; however, activation was
      observed under other conditions. NaCl, which lowers the non-critical micellar
      concentration (NCMC) of deoxycholate, caused significant decreases in control
      PLA2 activity in the absence of annexins, and greater decreases in PLA2 activity
      in annexin-containing samples, resulting in an apparent increase in inhibition.
      The PC/DOC substrate mixtures themselves appeared unstable. Despite a large
      excess of detergent, precipitates were, at times, observed upon incubation of
      some PC/DOC mixtures at 37 degrees C. Such behavior is of interest in view of the
      numerous reports of PLA2 inhibition by annexins and annexin-derived peptides in
      the PC/DOC system. The influence of the annexins on activity in this system is
      consistent with effects on the phase behavior of the PC/DOC mixture and/or
      competition with the enzyme for available Ca2+. These results caution against use
      of the PC/DOC system for analysis of potential PLA2 inhibitors unless the phase
      behavior of the system is more fully delineated.

PMID- 1387328
TI  - Pea dehydrins: identification, characterisation and expression.
AB  - An antiserum raised against dehydrin from maize (Zea mays) recognised several
      polypeptides in extracts of pea (Pisum sativum) cotyledons. A cDNA expression
      library was prepared from mRNA of developing cotyledons, screened with the
      antiserum and positive clones were purified and characterised. The nucleotide
      sequence of one such clone, pPsB12, contained an open reading frame which would
      encode a polypeptide with regions of significant amino acid sequence similarity
      to dehydrins from other plant species. The deduced amino acid sequence of the pea
      dehydrin encoded by B12 is 197 amino acids in length, has a high glycine content
      (25.9%), lacks tryptophan and is highly hydrophilic. The polypeptide has an
      estimated molecular mass of 20.4 kDa and pI = 6.4. An in vitro synthesised
      product from the clone comigrates with one of the in vivo proteins recognised by
      the antiserum. A comparison of the pea dehydrin sequence with sequences from
      other species revealed conserved amino acid regions: an N-terminal DEYGNP and a
      lysine-rich block (KIKEKLPG), both of which are present in two copies.
      Unexpectedly, pea dehydrin lacks a stretch of serine residues which is conserved
      in other dehydrins. B12 mRNA and dehydrin proteins accumulated in dehydration
      stressed seedlings, associated with elevated levels of endogenous abscisic acid
      (ABA). Applied ABA induced expression of dehydrins in unstressed seedlings.
      Dehydrin expression was rapidly reversed when seedlings were removed from the
      stress or from treatment with ABA and placed in water. During pea cotyledon
      development, dehydrin mRNA and proteins accumulated in mid to late embryogenesis.
      Dehydrin proteins were some of the most actively synthesised at about the time of
      maximum fresh weight and represent about 2% of protein in mature cotyledons.

PMID- 1387330
TI  - Comparison of antithrombin III, protein C and protein S levels in capillary and
      venous blood of newborn infants.
AB  - The plasma concentrations of antithrombin III, protein C and protein S in
      capillary and venous blood samples obtained simultaneously from 30 neonates were
      compared in order to determine the suitability of using capillary blood for
      estimation of these proteins with anticoagulant action. Our findings showed that
      while capillary and venous blood did not differ significantly in antithrombin III
      functional activity and protein C antigen levels, the capillary samples had
      significantly lower protein C functional activity and higher antithrombin III
      antigen level. Protein S antigen level was also significantly higher in the
      capillary samples although the difference was relatively small. The capillary and
      venous concentrations of the binding protein of protein S, C4b binding protein,
      were almost identical.

PMID- 1387329
TI  - Alterations in thrombin-induced protein tyrosine phosphorylation of platelets
      from patients with chronic myelogenous leukemia.
AB  - Thrombin is known to stimulate platelet protein tyrosine kinase (PTK). We studied
      thrombin-induced tyrosine-specific protein phosphorylation in normal platelets
      and those from patients with chronic myelogenous leukemia (CML) and other
      myeloproliferative disorders (MPD) using immunoblotting with antiphosphotyrosine
      (anti-P-Tyr) antibody. In resting platelets, two major phosphotyrosyl (P-Tyr)
      proteins with molecular masses of 120 kDa (p120) and 60 kDa (p60) were
      consistently detected both in normal subjects and in CML and other MPD patients.
      In addition to these P-Tyr proteins, a 36 kDa protein (p36) was predominantly
      phosphorylated only in CML platelets, using antilipocortin II antibody, we
      identified this p36 protein as lipocortin. Thrombin enhanced the tyrosine
      phosphorylation of p120 and p60, not only in normal platelets, but also in CML
      platelets, although the response was more delayed and the duration was shorter in
      CML platelets than those in normal platelets. Interestingly, decreased thrombin
      induced aggregation was associated with a transient stimulation of p36
      phosphorylation in CML platelets. These results suggest that the tyrosine
      phosphorylation of p36, which was probably identical to lipocortin, inhibits
      thrombin-induced platelet aggregation through anti-phospholipase A2 (anti-PLA2)
      activity.

PMID- 1387332
TI  - The incidence of DPB1 differences between serological and mixed lymphocyte
      culture matched unrelated individuals: implications for selection of bone marrow
      donors.
AB  - Bone marrow transplantation from unrelated donors is being used increasingly for
      the treatment of patients with leukaemia and other disorders of
      lymphohaemopoiesis. Selection of histocompatible unrelated bone marrow donors
      currently relies on serological HLA identity and negative mixed lymphocyte
      cultures (MLC) between potential donor-recipient pairs. Since serological HLA-DP
      typing is not feasible, we used the HLA-DPB1 oligonucleotide typing method to
      test whether the current selection procedure can also guarantee identity for HLA
      DP. In 40 consecutive patients, one-third (62/193) of the serologically HLA-A, 
      B, -C, -DR and -DQ identical donors were judged as MLC negative (relative
      response below 5%) with the presumptive recipient. HLA-DPB1 oligonucleotide
      typing of the MLC negative donors revealed that only one-third of these (20/62)
      were also identical for DP. In the majority of the pairs, we found a DPB1
      disparity. A difference in the graft-versus-host direction was seen in 25/62
      cases in the host-versus-graft direction in 28/62 cases and in both directions in
      29/62 cases. These data indicate that, in spite of the strict MLC criteria used,
      the current procedure did not guarantee complete MHC class II identity. Therefore
      oligotyping for DPB1 can improve matching for DP and should be introduced for
      typing of volunteers. We suspect that DP differences may contribute to the higher
      incidence of graft-versus-host disease or graft rejection in unrelated donor
      transplants.

PMID- 1387331
TI  - Atrial natriuretic peptide and fludrocortisone therapy in congenital adrenal
      hyperplasia.

PMID- 1387334
TI  - N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 blocks non-opioid
      stress-induced analgesia. II. Comparison across three swim-stress paradigms in
      selectively bred mice.
AB  - The effects of the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist
      MK-801 (dizocilpine, 0.075 mg/kg, i.p.) on swim-stress-induced analgesia (SSIA)
      were studied in control (C) mice and in mice selectively bred for high (HA) or
      low (LA) SSIA. In three consecutive experiments, animals were subjected to forced
      swimming at water temperature of 20 degrees C, 32 degrees C and 15 degrees C and
      the resulting analgesia (hot-plate test) was found to be mixed opioid/non-opioid,
      opioid and non-opioid, respectively, as a function of the degree of antagonism by
      naloxone (10 mg/kg, i.p.). The major finding of this study is that MK-801
      attenuated 15 degrees C SSIA, against which naloxone was ineffective, but had no
      effect on 32 degrees C SSIA, which naloxone blocked completely. A combination of
      naloxone and MK-801 significantly attenuated 20 degrees C SSIA in C and HA mice
      and in HA mice this attenuation was significantly larger than that produced by
      either drug alone. Morphine analgesia (10 mg/kg, i.p.) was unaffected by MK-801.
      It is concluded that low doses of MK-801 selectively block non-opioid mechanisms
      of SSIA.

PMID- 1387333
TI  - Mixed allogeneic chimeras prepared by a non-myeloablative regimen: requirement
      for chimerism to maintain tolerance.
AB  - We have recently described a non-myeloablative conditioning regimen permitting
      engraftment of allogeneic bone marrow in mice which involves administration of
      anti-CD4 (GK1.5) plus anti-CD8 (2.43) monoclonal antibodies in vivo, 3 Gy whole
      body irradiation, plus 7 Gy thymic irradiation. B10 (H-2b) mice prepared by this
      regimen and infused with unmanipulated B10.D2 (H-2d) bone marrow develop
      permanent mixed lymphohematopoietic chimerism and specific tolerance to donor
      skin grafts. We now demonstrate that mixed chimerism persists longer than 170
      days in the lymphoid tissues including spleen, thymus and bone marrow of such
      animals, and that equivalent levels of donor chimerism are observed in both T and
      B cell compartments. In addition stable mixed chimeras were found to be
      unresponsive to host (B10) and donor (B10.D2) stimulator cells in mixed
      lymphocyte reaction and in cell mediated lympholysis assays, while responses to a
      third party (B10.BR, H-2k) were intact. Persistent chimerism was found to be
      necessary for the maintenance of skin graft tolerance in these animals, since in
      vivo depletion of donor cells by treatment with an anti-H-2d (34-2-12) monoclonal
      antibody resulted in the subsequent rejection of donor skin grafts. These studies
      demonstrate that mixed allogeneic chimeras produced using this regimen are
      specifically tolerant to donor in vitro and in vivo, and that persistence of
      donor chimerism is critical for the maintenance of tolerance.

PMID- 1387336
TI  - Lipocortin-1 inhibits NMDA receptor-mediated neuronal damage in the striatum of
      the rat.
AB  - Lipocortin-1 (annexin-1), an endogenous phospholipid and calcium binding protein,
      has been shown to significantly attenuate the damage produced by focal cerebral
      ischaemia in the rat. In the present study we have therefore investigated its
      effect on N-methyl-D-aspartate (NMDA) induced neuronal damage. Unilateral
      intrastriatal infusion of a potent and selective NMDA agonist, cis-2,4
      methanoglutamate (MGlu), induced an extensive lesion of the striatum in the rat,
      which was inhibited (greater than 80%) by prior injection of MK801 (4 mg/kg,
      i.p.). Infusion of 1.2 micrograms of an active fragment of lipocortin-1 (N
      terminal 1-188 aa) immediately after MGlu significantly reduced the extent of
      damage by 44.2 +/- 8.0%. In contrast, infusion of 3 microliters of neutralizing
      anti-lipocortin-1 antibody with MGlu increased lesion size by 158.9 +/- 22.0%.
      These findings indicate that the damage produced by intrastriatal infusion of
      MGlu is mediated by the NMDA receptor. Lipocortin-1 fragment markedly attenuated,
      and the neutralizing antibody increased, this NMDA mediated neuronal damage.
      These observations may explain the neuroprotective action of lipocortin following
      cerebral ischaemia.

PMID- 1387335
TI  - Localization of dopamine D2 receptor protein in rat brain using polyclonal
      antibody.
AB  - The precise distribution of the dopamine type D2 receptor has been mapped for the
      first time in rat brain using an antibody to D2 receptor protein. Polyclonal
      antisera were collected from rabbits inoculated with an undecapeptide identical
      to residues 24-34 of the D2 protein sequence. Rat brain slices, 40 microns in
      thickness, were incubated with either primary antiserum, the antiserum plus free
      peptide antigen, or pre-immune serum. Antibody binding was visualized by
      peroxidase-antiperoxidase (PAP) reaction followed by light microscopy. PAP
      complex bound moderately-to-densely throughout the medial forebrain bundle, and
      was seen in more discrete regions in the midbrain, consistent with the binding of
      D2 radioligands. There were some unexpected results, namely in the cerebral
      cortex and nucleus accumbens, there were unexpectedly steep gradients in binding
      density, decreasing caudally; no binding was detected in the hippocampus or the
      substantia nigra pars reticulata. In all positive-staining regions examined, the
      antibody was highly localized to neuronal cell bodies, except in the frontal
      cortex where antibody was also evident on basilar dendrites. These data confirm
      that the polyclonal antibody recognized dopamine D2 receptor protein throughout
      the rat brain, and suggest that the D2 receptor is distributed more abundantly on
      somata than on cellular processes.

PMID- 1387338
TI  - The 'initial burst' of muscle spindle afferents with or without terminals on the
      bag1 intrafusal muscle fibre.
AB  - The initial burst has been re-examined following conditioning of the muscle to
      investigate its intrafusal origins. The burst was present in the response to
      stretch of spindle afferents that innervated the bag1 fibre and those that did
      not. There was, however, a difference in amplitude of the burst. These findings
      are discussed in terms of intrafusal mechanisms.

PMID- 1387337
TI  - The loss of beta II-protein kinase C in the striatum from patients with
      Huntington's disease.
AB  - We have examined the levels of protein kinase C (PKC) in autopsied brains of
      patients with Huntington's disease (HD), using [3H]4-beta-phorbol-12,13
      dibutyrate ([3H] PDBu) and antisera against the PKC subspecies. In the caudate
      nucleus and putamen from patients with HD, the specific binding for [3H]PDBu was
      significantly decreased by 74 and 68%, respectively, as compared to findings in
      controls. The beta II-PKC immunoreactivities were significantly reduced by 65%,
      whereas the alpha-PKC immunoreactivities increased by 146%, in the putamen. There
      were no differences in the beta I- or gamma-PKC immunoreactivities in the putamen
      between HD and controls. These results suggest the differential localization of
      four PKC subspecies in human striatum and the involvement of four subspecies in
      different aspects of HD pathophysiology.

PMID- 1387339
TI  - Antagonists of the NMDA receptor and allopurinol protect the olfactory cortex but
      not the striatum after intra-cerebral injection of kainic acid.
AB  - Overstimulation of the NMDA receptor, as well as generation of excessive amounts
      of free radicals, has been implicated in excitotoxic brain injuries. We report
      here that two antagonists of the NMDA receptor and an inhibitor of the free
      radical-generating enzyme, xanthine oxidase, protect the olfactory cortex but not
      the striatum after intrastriatal injection of kainic acid. Our results suggest
      the existence of a precise link between excitotoxic activation of the NMDA
      receptor and neuropathology related to excessive amounts of free radicals. The
      focal point of this link may be the entry of Ca2+ through the NMDA receptor and
      the consequent activation of proteases and free radical-generating systems.

PMID- 1387340
TI  - Effects of intra-amygdala injections of NMDA receptor antagonists on acquisition
      and retention of inhibitory avoidance.
AB  - These experiments examined the effects of intra-amygdala injections of NMDA
      receptor antagonists on the acquisition and retention of inhibitory avoidance. In
      Expt. I, rats received bilateral intra-amygdala injections of the NMDA
      antagonists D,L-AP5 (1-10 micrograms), D-AP5 (0.03-1 micrograms), CPP (0.125 or
      0.375 microgram), or MK-801 (0.2 or 0.5 microgram) prior to training in a
      continuous multiple-trial inhibitory avoidance (CMIA) task. Acquisition of the
      task was not significantly affected by any of the drug injections. In contrast,
      all three competitive antagonists, D,L-AP5, D-AP5 and CPP, produced dose
      dependent impairment of 48 h retention performance. Although the MK-801
      injections did not significantly impair retention performance, the retention
      scores of the 0.5 microgram MK-801 group were bimodally distributed, indicating
      retention impairment in a subgroup of the animals given that dose. Intra-amygdala
      injections of 3 or 10 micrograms D,L-AP5 did not affect footshock sensitivity
      (Expt. II) or locomotor activity (Expt. III) and their retention-impairing
      effects were not due to induction of state dependency (Expt. IV). The retention
      impairing effects of intra-amygdala injections of NMDA antagonists were not due
      to diffusion of the drugs dorsally: injections of 1 microgram D-AP5 into the
      striatal area directly above the amygdala impaired acquisition but not retention
      performance (Expt. V). The retention-impairing effects of 1 microgram D-AP5 or
      0.5 microgram MK-801 were attenuated by giving additional training to the animals
      shortly after receiving intra-amygdala injections (Expt. VI). The implications of
      these findings for hypotheses concerning amygdala function in learning and memory
      are discussed.

PMID- 1387341
TI  - A 1992 update on hepatitis B vaccination.
AB  - Surveillance studies of people at high risk for hepatitis B, combined with almost
      10 years of experience with the vaccine, have allowed cost effective vaccination
      programs to be devised. It would make good sense to incorporate the hepatitis B
      vaccination into the standard childhood immunization protocols. Present
      teenagers, who will not benefit from such a program, would be well advised to be
      vaccinated. All clinical dental staff should also be immunized. These three
      actions would be very effective in curbing the spread of this preventable
      disease.

PMID- 1387342
TI  - Estimates of costs and effects of screening for colorectal cancer in the United
      States.
AB  - BACKGROUND: In many ways, colorectal cancer might be an excellent candidate for
      mass screening because of the following: (1) it is the second leading cause of
      cancer mortality in the United States; (2) it develops slowly from a precursor
      lesion; and (3) methods of early detection are available. Barriers to screening
      include unproven efficacy of the procedure and high costs. METHODS: Cost analyses
      are derived from two mathematic models that estimate screening costs and effects
      based on expert opinion and data from uncontrolled screening studies. RESULTS:
      One screening option that follows the guidelines of the American Cancer Society
      and the National Cancer Institute (annual testing for occult fecal blood and
      sigmoidoscopy every 5 years) could result in a 40% decrease in colon cancer
      mortality for American adults between the ages of 50 and 75 years if they comply
      with screening. This model, developed by David Eddy, projects an average of 44
      days of extra life per person screened, at a net cost of $57 per day of life
      gained. Using assumptions much less favorable to screening, the Office of
      Technology Assessment modeled this same screening strategy for those aged 65
      years and older. This model predicted a similar benefit of extra life per person
      at a cost of $118 per day of life gained. This doubling of the predicted cost was
      caused by the inclusion of subsequent colonoscopic surveillance costs for those
      found to have polyps. Direct costs of screening annually for fecal occult blood
      and every 5 years by sigmoidoscopy would cost an average of approximately $48 per
      person per year for screening and follow-up testing of all positive results.
      Fecal occult blood testing alone, although less effective, costs only $20 per
      person per year, including follow-up testing of all positive findings.
      CONCLUSIONS: The results from randomized trials of fecal occult blood screening
      will be known in the next 5 years, but trials of screening with sigmoidoscopy
      will not be complete for 10-15 years. Because mass screening programs will be
      difficult to fund without better data on their efficacy, colorectal cancer
      screening will continue to be a matter of individual decision making in the
      clinical setting for years to come. Clearer presentations of costs and benefits
      that can be understood by both patients and physicians are needed.

PMID- 1387343
TI  - Inhibition of spontaneous testicular Leydig cell tumor development in F-344 rats
      by dehydroepiandrosterone.
AB  - The incidence of spontaneous Leydig cell tumors of testis is very high in old F
      344 rats. We have examined the effect of dehydroepiandrosterone (DHEA), a steroid
      hormone with antimitotic and anticarcinogenic properties, on spontaneous Leydig
      cell tumorigenesis. Fifteen-week-old male F-344 rats were fed a diet containing
      DHEA (0.45% w/w) for 84 weeks. At the termination of experiment none of the 13
      rats had Leydig cell hyperplasia or Leydig cell tumors. All the eight control
      rats of comparable age had Leydig cell tumors. These findings suggest that DHEA
      is a potent inhibitor of spontaneous Leydig cell tumors of testis in aged rats.

PMID- 1387344
TI  - In search of specific cytotoxic T lymphocytes infiltrating or accompanying human
      ovarian carcinoma.
AB  - Lymphocytes infiltrating human ovarian carcinoma obtained directly from the
      tumour mass (tumour-infiltrating lymphocytes, TIL) or from the carcinomatous
      ascites (tumour-associated lymphocytes, TAL) were expanded in vitro in long-term
      cultures with interleukin-2 and tested for their specific cytolytic activity.
      Killing of the autologous tumour was detected only in a proportion of the
      patients, less frequently in TIL compared to TAL. In fact two out of ten TIL and
      four out of nine TAL cultures tested showed significant levels of lysis against
      the autologous tumour. This cytotoxic activity was not restricted to the
      autologous tumour, as other tumour cell lines, including non-ovarian ones, were
      lysed as well. The cultures that were not cytotoxic against the autologous tumour
      were in most cases able to lyse other tumour cell lines of ovarian or other
      histology. Cloning of TIL from one patient was performed: of 22 clones tested, 4
      displayed higher cytotoxicity against the autologous tumour compared to the
      uncloned population and 3 out of these 4 did not kill an irrelevant carcinoma
      cell line. In order to stimulate the expansion of putative specific effectors we
      performed mixed lymphocyte/tumour cultures (MLTC) with autologous or allogeneic
      tumour cells. No stimulation of cytotoxicity against the autologous tumour was
      detected after MLTC in nine different TAL populations, using autologous or
      allogeneic tumours as stimulators. On the contrary, peripheral blood lymphocytes
      from two patients after MLTC with the autologous tumour showed increased killing
      of the autologous and decreased killing of an allogeneic target. In conclusion
      TIL and TAL from ovarian carcinoma expanded in vitro with interleukin-2 usually
      have non-MHC-restricted cytotoxicity and variable degrees of reactivity against
      the autologous tumour. A preferential killing for the autologous tumour was not
      observed even after MLTC. These results do not exclude the existence of tumour
      specific cytotoxic T lymphocytes in ovarian carcinoma; nevertheless they suggest
      that putative specific effectors have very low frequency and that culture
      techniques for expanding their growth more selectively are still to be optimized.

PMID- 1387345
TI  - Role of arterial hypertension in left ventricle hypertrophy in hemodialysis
      patients: an echocardiographic study.
AB  - To assess the role of arterial hypertension in left ventricle (LV) hypertrophy
      among hemodialysis patients, echocardiographic evaluation was performed in 10
      hypertensive and 13 normotensive hemodialysis subjects matched for age, sex,
      race, duration of dialysis treatment and degree of interdialytic volume
      expansion. We excluded from the latter group patients with previous hypertension
      since hypertensive heart disease may persist after adequate blood pressure
      control. We also studied 17 normal controls and 10 non-uremic patients with
      essential hypertension. Comparisons between the two uremic groups showed that the
      hypertensive patients had a higher mass index (222 +/- 74 x 108 +/- 26, p =
      0.0001) and posterior wall thickness (12 +/- 2 x 9 +/- 2, p = 0.0001) and a
      reduced LV radius/wall thickness ratio (4.4 +/- 0.7 x 5.8 +/- 1, p = 0.0001).
      There were no significant echocardiographic differences between normal controls
      and normotensive uremics. In contrast, compared to controls, hypertensive uremic
      patients showed an increased LV mass index (222 +/- 74 x 83 +/- 21, p = 0.0001)
      and posterior wall thickness (12 +/- 2 x 7 +/- 1, p = 0.0001) and a reduced LV
      radius/wall thickness ratio (4.4 +/- 0.7 x 6.5 +/- 1.1, p = 0.001),
      characterizing concentric hypertrophy. They also had ventricular dilation with
      larger LV dimensions than in controls (53 +/- 5 x 47 +/- 4, p = 0.004). In
      patients with essential hypertension, the mass index (135 +/- 22), wall thickness
      (11 +/- 1) and LV radius/wall thickness ratio (4.3 +/- 0.7) significantly
      differed (p = 0.0001) from those in the controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1387346
TI  - Augmented plasma protein C activity after coronary thrombolysis with urokinase in
      patients with acute myocardial infarction.
AB  - Coronary thrombolysis reduces morbidity and mortality in patients with acute
      myocardial infarction, however, the exact effects of thrombolytic agents on the
      status of intrinsic hemostases are not fully understood. In the present study, we
      examined serial changes in plasma thrombin and protein C activities of 6 patients
      with acute myocardial infarction treated with urokinase. Fibrinolysis occurred
      immediately after urokinase injection with an increase in the plasma thrombin
      antithrombin III complex, suggesting a subsequent procoagulant state due to
      thrombin generation. Correspondent increases in plasma protein C activity were
      observed, however, protein S levels did not change at all. Our findings suggest
      that urokinase administration for coronary thrombolysis not only causes
      fibrinolysis, but also induces thrombin activity, which may be antagonized by
      augmented intrinsic protein C activity.

PMID- 1387347
TI  - MHC-unrestricted recognition of bacteria-infected target cells by human CD8+
      cytotoxic T lymphocytes.
AB  - A CD8+ alpha beta TCR+ T cell clone (A35) was isolated from the synovial fluid of
      a patient with post-enteric reactive arthritis caused by Yersinia enterocolitica.
      This clone efficiently killed autologous and allogeneic target cells that had
      been preincubated with live but not with heat-killed bacteria. There was no
      restriction by polymorphic parts of HLA-A, -B, or -C molecules and a HLA class II
      deficient mutant cell line was lysed as efficiently as its normal counterpart,
      whereas infected HLA class I-deficient cells (Daudi cells) were not. The clone
      showed crossreaction between Yersinia enterocolitica, Escherichia coli,
      Pseudomonas aeruginosa, and Streptococcus pyogenes, but did not lyse target cells
      preincubated with Staphylococcus epidermidis. MAb to CD2, CD3, and CD8
      efficiently blocked A35, whereas the addition of mAb to HLA class II or to HLA
      class I did not. This clone apparently represents a novel effector mechanism
      against bacteria-infected or -modified cells that could be involved in the
      immunopathology of reactive arthritis.

PMID- 1387348
TI  - Nonspecific regulatory mechanism of contact sensitivity: nonspecific suppressor
      factor (NSF)-treated intermediate cells produce a second nonspecific suppressor
      factor (NSFint).
AB  - Nonspecific suppressor factor (NSF), which inhibits the passive transfer of
      contact sensitivity (CS), is produced spontaneously from macrophage-like
      suppressor cells induced by intravenous administration of oxazolone (Ox)
      conjugated spleen cells. NSF binds selectively to Ia-positive, cyclophosphamide
      (CY)-sensitive, and plastic-adherent cells (named intermediate cells) present in
      the normal spleen. NSF-treated intermediate cells acquire the ability to suppress
      the passive transfer of CS nonspecifically. In this study, NSF-treated
      intermediate cells were found to release a second nonspecific suppressor factor
      (NSFint) during a 2-hr culture, while retaining their suppressor activity.
      Investigation of the relationship between these two factors showed that both NSF
      and NSFint were trypsin-sensitive, nondialyzable proteins. However, gel
      chromatography revealed that NSF was about 43 kDa, while NSFint was about 20 kDa.
      NSF was released from macrophage-like suppressor cells after RNA-dependent
      protein synthesis. In contrast, production of NSFint was energy dependent but did
      not require protein synthesis. Intermediate cells pretreated with lysosomotropic
      agents, such as ammonium chloride or chloroquine, did not acquire suppressor
      activity nor release suppressor factors due to NSF treatment. These observations
      suggest that NSFint is an altered form of NSF released by the intermediate after
      having undergone some modification; the biochemical mechanism is not known. This
      study showed that the intermediate cells play an active role in the suppressor
      cascade of NSF.

PMID- 1387349
TI  - Antigen concentration determines helper T cell subset participation in IgE
      antibody responses.
AB  - A recently developed in vitro system for antigen-stimulated primary and secondary
      murine IgE antibody responses has been used to define (a) the relative
      participation of the Th1 and Th2 cell-derived lymphokines IFN-gamma and IL-4,
      respectively, in such responses, and (b) the role of antigen concentration in
      determining functional helper T cell activity. These studies confirm that IL-4
      and IFN-gamma exert regulatory effects on IgE synthesis, but the nature and
      extent of their respective effects on primary and secondary IgE responses differ.
      Thus, primary IgE responses are considerably more sensitive to and dependent on
      IL-4 than are secondary IgE responses since (1) anti-IL-4 monoclonal antibody
      totally inhibited primary IgE responses, but only partially affected secondary
      responses; and (2) exogenously added IL-4 could stimulate primary IgE responses
      to optimal antigen concentrations, but had no effect on secondary IgE production.
      Likewise, antigen-stimulated primary IgE responses are about eightfold more
      sensitive than are secondary responses to the inhibitory effects of IFN-gamma.
      Studying the effect of antigen dose on the quantity of IgE antibody produced
      revealed that although IFN-gamma could be detected by ELISA in cultures
      exhibiting high-dose antigen-dependent diminution of IgE production, anti-IFN
      gamma monoclonal antibody could not reverse this phenomenon. Thus, IFN-gamma is
      not solely responsible for decreased IgE synthesis associated with high-dose
      antigen exposure. IL-4 activity was detected in the fluid from cultures
      stimulated with low, but not high, levels of antigen. Moreover, addition of
      exogenous IL-4 restored IgE production to normal levels in cultures exposed to
      high antigen concentrations. Therefore, it appears that high levels of antigen
      result in selective stimulation of Th1 cells which produce IFN-gamma, and
      diminished activation of IL-4-producing Th2 cells. These results help explain
      observations regarding the influence of antigen dose on the generation of
      experimental and clinical IgE antibody responses in vivo.

PMID- 1387350
TI  - Alloreactivity against IE-encoded antigens: evidence of the discrepancy between
      graft rejection and reactivity of IE-reactive T cells.
AB  - Participation of IE antigens (Ag) in immune response as the transplantation Ag
      was examined. IE- B10.A(4R)(4R; Kk, IAk, IE-, Db) mice could not reject skin
      graft from IE Ag alone-disparate B10.A(2R) (2R; Kk, IAk, IEk, Db) mice despite
      intravenous (iv) injection of 2R spleen cells (SC) before or after skin grafting,
      indicating that graft rejection could not be caused across IE Ag-barrier alone.
      Furthermore, 4R SC could not induce lethal graft-versus-host disease (GVHD) in
      supralethally (950 rad) irradiated 2R mice. On the other hand, infiltration of
      lymphoid cells was observed at the site of transplanted 2R skin in 4R mice. SC of
      4R mice unprimed or primed with 2R skin or 2R SC showed the capability to
      proliferate in vitro in response to 2R Ag. In immunofluorescence analysis of
      lymph node cells (LNC) of 4R mice injected iv with 2R SC 7 days earlier, IE
      reactive CD4+Vbeta 11+ T cells did not change in number, but slightly increased
      the expression of interleukin-2 receptor (IL-2R). In 2R mice irradiated with 670
      rad and injected iv with 4R SC 7 days earlier, 4R-derived CD4+V beta 11+ T cells
      proliferated, changed to blastoid form, and showed a markedly increased
      expression of IL-2R. To further investigate the influence of IE alloantigens on
      transplantation immunity, IL-2 production and anti-class I CTL activity were
      assayed. The 4R SC capable of recognizing IEk and Dk Ag of B10.BR (Kk, IAk, IEk,
      Dk) generated levels of both IL-2 and CTL activities higher than those of 2R SC
      capable of recognizing Dk Ag alone. These results strongly suggest that IE
      alloantigens indirectly act as the transplantation Ag by the stimulation of IE
      reactive CD4+ helper T cells resulting in the differentiation of class I
      restricted CD8+ T cells.

PMID- 1387351
TI  - Comparative absorption and distribution pharmacokinetics of intravenous and
      epidural sufentanil for major abdominal surgery.
AB  - The pharmacokinetics of absorption and distribution of a single bolus dose of
      sufentanil 150 micrograms for major abdominal surgery were compared in 20
      patients after random intravenous or epidural administration. Samples of plasma
      and cerebrospinal fluid were taken at regular intervals from time zero to 180 min
      after injection and at the time of tracheal extubation (3.43 to 12.66h).
      Sufentanil was analysed by radioimmunoassay. The area under the concentration
      time curve (AUC) from zero to 1h, 2h, 3h, tracheal extubation and infinity, the
      absorption and distribution half-lives, maximum plasma and CSF concentrations,
      time to the peak concentration of sufentanil, and the fraction of sufentanil that
      reached the central circulation after epidural administration were assessed.
      Except in the first sample, plasma concentrations of sufentanil were comparable
      between the 2 groups. The initial transfer of sufentanil from the epidural space
      to the systemic circulation appeared to be very rapid. Explanations for this
      phenomenon are given. In only 3 patients could an uptake of sufentanil from the
      systemic circulation into the CSF be demonstrated. The transfer of sufentanil
      from the epidural space into the CSF is slower than the transfer into the plasma
      and it varied interindividually.

PMID- 1387352
TI  - Advances in occupational asthma.
AB  - Clinical and research interests in occupational asthma increased dramatically in
      the 1980s. Advances in our knowledge base have led to improved recognition,
      management, and methods for preventing this disorder. An accelerated pace of
      basic and clinical research is anticipated in the 1990s. These efforts will
      likely lead to a more complete understanding of the disease (and pay dividends in
      understanding asthma itself). Occupational asthma is predicted to be the
      preeminent occupational lung disease in the next decade.

PMID- 1387354
TI  - Effects of anabolic-androgenic steroids on the pilosebaceous unit.
AB  - Examination of skin biopsy specimens from persons using anabolic-androgenic
      steroids demonstrates dramatic hypertrophy of the sebaceous glands. High dosages
      of testosterone and anabolic-androgenic steroids, often self-administered by
      athletes, increase skin surface lipids, the cutaneous population of
      Propionibacteria acnes and the cholesterol and free fatty acids of the skin
      surface lipids. Acne, oily hair and skin, sebaceous cysts, hirsutism, androgenic
      alopecia, striae atrophicae, seborrheic dermatitis, and secondary infections
      including furunculosis may occur in persons using these drugs.

PMID- 1387353
TI  - Can midazolam diminish sufentanil analgesia in patients with major trauma? A
      retrospective study with 43 patients.
AB  - Benzodiazepine agonists in combination with opioid analgesics are commonly used
      for combined analgesia and sedation in intensive care patients as well as for
      anesthesia. In animals, studies indicate either agonistic or antagonistic
      interactions of benzodiazepine agonists and opioids. This retrospective study of
      43 patients evaluated the possible clinical relevance of benzodiazepine-opioid
      interactions related to pain management. We observed an increase of greater than
      50% of the maximal sufentanil infusion rate in significantly more patients in
      group 2 (13 patients vs 6 patients; chi 2: p = 0.04) and a decrease of the
      sufentanil infusion rate in eight group 1 patients, but only in one patient in
      group 2 (chi 2: p = 0.03). We believe that an interaction between midazolam and
      sufentanil on nociceptive transmission and/or a rapid development of tolerance to
      sufentanil may be responsible for the observed difference. Contrary to the common
      clinical impression that midazolam potentiates opioid analgesia, these results
      indicate that systemic co-administration of midazolam over a period of more than
      three days can diminish sufentanil efficacy.

PMID- 1387355
TI  - Acne mechanica in athletes.
AB  - Acne mechanica is a papulopustular eruption caused by the physical factors of
      pressure, occlusion, friction, and heat acting upon the skin, either separately
      or in unison. Athletes in certain sports are at particular risk for this
      condition. Dermatologists, if familiar with its presentation, can play a critical
      role in relieving its distracting symptoms during a competitive season, and
      eliminating it completely at the season's end.

PMID- 1387356
TI  - Simple management of plantar clavi.

PMID- 1387357
TI  - Acne keloidalis aggravated by football helmets.

PMID- 1387358
TI  - Pelvic peritoneal reconstruction to prevent radiation enteritis in rectal
      carcinoma.
AB  - Some patients with rectal cancer who undergo exenterative surgery may require
      radiation therapy as an adjuvant treatment for recurrent or residual disease. A
      common devastating side effect of this treatment modality is radiation enteritis,
      a radiation-induced small bowel injury. Hence, the prevention of such a
      complication is essential for both the surgeon and the radiation oncologist. A
      new surgical method using the posterior rectus sheath and peritoneum to partition
      the abdominal cavity at the level of the umbilicus to the sacral promontory seems
      to accomplish this purpose, keeping the small bowel away from the pelvic cavity.
      After removal of the rectal lesion [eight abdominoperineal resections (APRs),
      nine Hartmann's procedures, and one low anterior resection (LAR)] in 18 patients
      with rectal cancer, this new surgical procedure was performed. One of the
      patients had an early postoperative intestinal obstruction, and all but one of
      the patients received postoperative adjuvant radiation therapy. In addition, a
      small bowel series was performed before the radiation therapy and six months and
      one year after surgery. Upon examination, most of these patients still had their
      small bowel kept intact in the abdominal cavity. During the follow-up period of
      10 months to 2 years with an average of 18 months, two late complications of
      intestinal obstruction were noted. Exploratory laparotomy of these two patients
      revealed radiation enteritis of the small bowel. Therefore, the failure rate of
      the following procedure is 12 percent, since 2 of the 17 patients received small
      bowel injury. Although the follow-up period for this surgical method is short,
      the results have encouraged us to continue the use of this procedure on advanced
      rectal cancer patients who require postoperative radiation therapy.

PMID- 1387359
TI  - The effect of phospholipids, calcium ions and protein S on rate constants of
      human factor Va inactivation by activated human protein C.
AB  - Rate constants for human factor Va inactivation by activated human protein C
      (APC) were determined in the absence and presence of Ca2+ ions, protein S and
      varying concentrations of phospholipid vesicles of different lipid composition.
      APC-catalyzed factor Va inactivation in free solution (in the presence of 2 mM
      Ca2+) was studied under first-order reaction conditions with respect to both APC
      and factor Va and was characterized by an apparent second-order rate constant of
      6.1 x 10(5) M-1 s-1. Stimulation of APC-catalyzed factor Va inactivation by
      phospholipids was dependent on the concentration and composition of the
      phospholipid vesicles. Optimal acceleration (230-fold) of factor Va inactivation
      was observed with 10 microM phospholipid vesicles composed of 20 mol%
      dioleoylglycerophosphoserine (Ole2GroPSer) and 80 mol%
      dioleoylglycerophosphocholine (Ole2GroPCho). At higher vesicle concentrations and
      at higher molar fractions of Ole2GroPSer some inhibition of APC-catalyzed factor
      Va inactivation was observed. Membranes that contained anionic phospholipids
      other than phosphatidylserine also promoted factor Va inactivation. The ability
      of different anionic lipids to enhance factor Va inactivation increased in the
      order phosphatidylethanolamine less than oleic acid less than phosphatidic acid
      less than phosphatidylglycerol less than phosphatidylmethanol less than
      phosphatidylserine. APC-catalyzed factor Va inactivation in the presence of
      phospholipid vesicles could be saturated with respect to factor Va and the
      reaction obeyed Michaelis-Menten kinetics. Both the Km for factor Va and the Vmax
      of factor Va inactivation were a function of the phospholipid concentration. The
      Km increased from 1 nM at 2.5 microM phospholipid (Ole2GroPSer/Ole2GroPCho 20:80,
      mol/mol) to 65 nM at 250 microM phospholipid. The Vmax increased from 20 mol
      factor Va inactivated.min-1.mol APC-1 at 2.5 microM phospholipid to 62 mol factor
      Va inactivated.min-1.mol APC-1 at 10 microM phospholipid and remained constant at
      higher phospholipid concentrations. Protein S appeared to be a rather poor
      stimulator of APC-catalyzed factor Va inactivation. Protein-S-dependent rate
      enhancements were only observed in reaction mixtures that contained negatively
      charged phospholipid vesicles. Independent of the concentration and the lipid
      composition of the vesicles, protein S caused a twofold stimulation of APC
      catalyzed factor Va inactivation. This suggests that, in the human system,
      enhancement of APC binding to phospholipid vesicles by protein S is of minor
      importance. Considering that protein S is a physiologically essential
      antithrombotic agent, it is likely that other factors or phenomena contribute to
      the in vivo antithrombotic action of protein S.

PMID- 1387360
TI  - Modulation of cell-surface transferrin receptor by the imino sugar N
      butyldeoxynojirimycin.
AB  - The imino sugar, N-butyldeoxynojirimycin, is an inhibitor of the glycoprotein
      processing enzyme glucosidase I and exhibits anti-(human immunodeficiency virus)
      activity in vitro. We have investigated the effect(s) of this compound on cell
      surface glycoproteins by flow cytometry. We observed selective modulation of the
      transferrin receptor in response to treatment with 0.5 mM N-butyldeoxynojirimycin
      resulting in reduced cell-surface transferrin-receptor expression. The receptor
      modulation was dose dependent, resulted in reduced 59Fe uptake by treated cells
      and was fully reversible within 24 h of culture in the absence of the compound.
      Pulse/chase analysis in conjunction with endoglycosidase-H digestion demonstrated
      that transferrin-receptor glycosylation was altered following N
      butyldeoxynojirimycin treatment, which is compatible with glucosidase inhibition.
      In addition, modulation of transferrin receptor in response to N
      butyldeoxynojirimycin was not confined to a single cell line, but was also
      observed with certain human lymphoid and myeloid cell lines. Mechanism(s) of
      action of the imino sugar resulting in reduced cell-surface transferrin-receptor
      expression are discussed.

PMID- 1387361
TI  - Role of F0 and F1 subunits in the gating and coupling function of mitochondrial
      H(+)-ATP synthase. The effect of dithiol reagents.
AB  - A study is presented on the role of F0 and F1 subunits in oligomycin-sensitive H+
      conduction and energy transfer reactions of bovine heart mitochondrial F0F1 H(+)
      ATP synthase. Mild treatment with azodicarboxylic acid bis(dimethylamide)
      (diamide) enhanced oligomycin-sensitive H+ conduction in submitochondrial
      particles containing F1 attached to F0. This effect was associated with
      stimulation of the ATPase activity, with no effect on its inhibition by
      oligomycin, and depression of the 32Pi-ATP exchange. The stimulatory effect of
      diamide on H+ conduction decreased in particles from which F1 subunits were
      partially removed by urea. The stimulatory effect exerted by diamide in the
      submitochondrial particles with F1 attached to F0 was directly correlated with a
      decrease of the original electrophoretic bands of a subunit of F0 (F0I-PVP
      protein) and the gamma subunit of F1, with corresponding formation of their cross
      linking product. In F0 liposomes, devoid of gamma subunit, diamide failed to
      stimulate H+ conduction and to cause disappearance of F0I-PVP protein, unless
      purified gamma subunit was added back. The addition to F0 liposomes of gamma
      subunit, but not that of alpha and beta subunits, caused per se inhibition of H+
      conduction. It is concluded that F0I-PVP and gamma subunits are directly involved
      in the gate of the F0F1 H(+)-ATP synthase. Data are also presented indicating
      contribution to the gate of oligomycin-sensitivity conferral protein and of
      another protein subunit of F0, F6.

PMID- 1387362
TI  - Interaction of membranes of the Golgi complex with microtubules in vitro.
AB  - We have developed an in vitro assay for characterizing the binding of elements of
      the Golgi complex to microtubules. The binding assay comprises three distinct
      components, Golgi elements purified from Vero cells by subcellular fractionation,
      taxol-polymerized tubulin from bovine brain coupled to magnetic beads and cytosol
      from HeLa cells. Binding of Golgi elements to microtubules is quantitated by
      measuring the activity of the Golgi marker enzyme, galactosyltransferase,
      associated with the microtubule-coated beads retrieved with a magnet. In the
      presence of cytosol, 35 to 45% of the total input of galactosyltransferase
      activity (Golgi elements) bind to microtubules; only 3% of the Golgi elements
      bind to microtubules, however, in the absence of cytosolic factors. This binding
      is saturable at a cytosol concentration of approximately 5 mg/ml or at a high
      input of Golgi elements. Cytosol-stimulated binding of Golgi elements to
      microtubules is decreased to less than 15% when cytosol is pretreated with 2 mM N
      ethylmaleimide (NEM) and it is abolished when cytosolic proteins are inactivated
      by heat or when microtubules have been coated with heat-stable microtubule
      associated proteins (MAPs). Trypsinization of the membranes of the Golgi elements
      abolishes their ability to bind to microtubules. Furthermore, inactivation of
      cytoplasmic dynein by UV/vanadate treatment does not affect the binding. This
      suggests that the interaction of Golgi elements with microtubules depends on NEM
      sensitive cytosolic factors and membrane-associated receptors, but not on the
      microtubule-based motor protein cytoplasmic dynein.

PMID- 1387364
TI  - Protein immunolocalization in the spread erythrocyte membrane skeleton.

PMID- 1387363
TI  - Stimulation of the biosynthesis of lactosamine repeats in glycoproteins in
      differentiating U937 cells and its suppression in the presence of NH4Cl.
AB  - We prepared a mouse monoclonal antibody, 2D5, which recognized a highly
      glycosylated human lysosomal membrane antigen. The apparent molecular mass of
      this antigen was cell type dependent and ranged between 100 kDa and 130 kDa. The
      difference was due to a variation in the carbohydrate moiety, since upon removal
      of the N-linked oligosaccharides the size of the glycoprotein was reduced to
      approximately 50 kDa in all cases. The high carbohydrate contents, subcellular
      localization and N-terminal sequence indicated a high similarity or identity of
      this antigen with the lamp-2 protein. In U937 cells several agents known to
      elicit differentiation induced synthesis of a larger form of the lamp antigen.
      Thus, treatment of cells with calcitriol resulted in a shift in its average
      molecular mass from 115 kDa to 130 kDa. The difference was due to an increase in
      the contents of lactosamine repeats. In subcellular membranes from calcitriol
      treated cells the specific activity of the UDP-N-acetylglucosamine: N
      acetyllactosamine N-acetylglucosaminyltransferase was enhanced 3-fold. The
      enhancement was accompanied with an elongation of lactosamine repeats in N-linked
      oligosaccharides in the 46 kDa mannose 6-phosphate receptor and the homing
      receptor, the leucocyte antigen CD44. In contrast, the apparent size of the
      leucocyte antigen CD43 which bears numerous O-linked oligosaccharides was not
      changed indicating a selectivity in the modulation of the formation of
      lactosamine repeats in N- and O-linked carbohydrates. It is shown further that
      the synthesis of lactosamine repeats in U937 cells is impeded in the presence of
      NH4Cl.

PMID- 1387365
TI  - Selective screening on hormonedependent tumours of women's reproductive system
      organs.
AB  - This work is devoted to research on the selective screening possibilities of
      hormonodependent tumours of the female reproductive system organs (endometrial
      cancer, ovarian cancer, breast cancer). After morbidity analysis using case
      control study elucidation of risk factors affecting cancer of the uterine cervix,
      endometrium, ovary and breast were carried out on of female population the
      Ashkhabad (311 cancer patients and 14872 healthy women). Using established risk
      factors and mathematical methods optimized computer programmes were developed
      processing individual risk and models forming risk groups or hormonedependent
      tumours which were used in practice. As a result in the risk group were found
      0.9% subclinical states and hormonedependent tumours (control -0.16%). The
      research accomplished has shown the practical importance of hormonedependent
      selective screening and necessity of elucidating new disease-epidemiological and
      laboratory risk factors in cancer of the reproductive system's organs.

PMID- 1387366
TI  - Synergistic release of calcium in sea urchin eggs by caffeine and ryanodine.
AB  - A transient rise in intracellular Ca2+ during fertilization is necessary for
      activation of the quiescent sea urchin egg. Several mechanisms contribute to the
      rise in Ca2+ including influx across the egg plasma membrane and release from
      intracellular stores. The egg contains both IP3-sensitive and -insensitive Ca2+
      release mechanisms and in this study we have used single-cell spectrofluorimetry
      to examine the effects of caffeine and ryanodine on Ca2+ release in eggs
      preloaded with fura 2. Caffeine induced a small Ca2+ release that was insensitive
      to heparin or ruthenium red. Ca2+ liberation by caffeine could be augmented by
      prior treatment with thapsigargin, an inhibitor of endoplasmic reticulum Ca2+
      ATPase. Variable Ca2+ releases were observed in response to microinjection of
      ryanodine. The action of ryanodine appeared to be enhanced by prior injection of
      heparin and partially inhibited by ruthenium red. The release of Ca2+ by caffeine
      or ryanodine was generally insufficient to trigger cortical granule exocytosis,
      thus these eggs could be fertilized and a second Ca2+ release during
      fertilization was measured. Unlike the caffeine- and ryanodine-sensitive Ca(2+)
      induced Ca2+ release mechanism in somatic cells, the graded responses in eggs
      suggested this caffeine- and ryanodine-sensitive release mechanism is not
      sensitive to sudden changes in Ca2+. Thus we could examine the combined actions
      of caffeine and ryanodine on Ca2+ release, which were synergistic. Caffeine
      treatment of ryanodine-injected eggs or ryanodine injection of caffeine-treated
      eggs stimulated a Ca2+ release significantly larger than the release by either
      drug independently. The experiments presented here suggest that sea urchin eggs
      liberate Ca2+ in response to caffeine and ryanodine; however, the regulation of
      this release differs from that described for caffeine- and ryanodine-sensitive
      Ca(2+)-induced Ca2+ release of somatic cells.

PMID- 1387367
TI  - Lys-373 of actin is involved in binding to caldesmon.
AB  - Limited proteolysis of actin with trypsin removes its two or three C-terminal
      amino acid residues [Proc. Natl. Acad. Sci. USA 81 (1984) 3680-3684].
      Carboxypeptidase B-treatment of G- and F-actin previously digested with trypsin
      revealed that in the first case preferential release of three and in the second
      two C-terminal amino acid residues takes place. Tryptic removal of three but not
      two C-terminal amino acid residues of actin causes weakening of its interaction
      with caldesmon and lowering of the caldesmon-induced inhibitory effect on
      actomyosin ATPase activity. Therefore, it is concluded that the third amino acid
      residue from the C terminus of actin, Lys-373, is important for the interaction
      with caldesmon.

PMID- 1387368
TI  - Aromatase inhibitors: clinical pharmacology and therapeutic implications in
      breast cancer.
AB  - Aminoglutethimide was the first aromatase inhibitor to be used in breast cancer
      therapy but, since it interacts with the synthetic glucocorticoids,
      hydrocortisone must also be given as a replacement. The most important side
      effects of aminoglutethimide are at the level of the central nervous system.
      Other aromatase inhibitors with greater potency and selectivity are being
      developed. Pyridoglutethimide, a compound resulting from modifications to the
      structure of aminoglutethimide, seems to be devoid of sedative properties
      according to preliminary tests on the central nervous system. 4
      Hydroxyandrostenedione is significantly more potent and better tolerated than
      aminoglutethimide. Fadrozole (CGS 16,949 A) is 200-400 times more potent than
      aminoglutethimide and is now in phase II of its clinical development. CGS 20,267
      has no effect on adrenal steroidogenesis and is currently in phase I of its
      clinical development. Availability of newer aromatase inhibitors could make a
      worthwhile contribution to endocrine therapy in breast cancer.

PMID- 1387369
TI  - Isradipine in the treatment of peripheral occlusive vascular disease of the lower
      limbs: a pilot study.
AB  - The long-term effects of isradipine on peripheral occlusive vascular disease of
      the lower limbs were investigated in 23 normotensive patients with stable
      Fontaine stage IIa disease and with an absolute pain-free interval (treadmill
      speed 4 km/h, no incline) of 300 - 700 m, and Doppler ankle - arm arterial
      pressure index of less than 0.80 in at least one leg. Using a double-blind,
      parallel-group design, patients received either 2.5 mg isradipine twice daily or
      placebo for 12 months. Both isradipine (n = 11) and placebo (n = 12) increased
      the absolute pain-free interval mean values; the increases were not significantly
      different. Similar trends were observed in the mean values for relative pain-free
      interval and ankle--arm arterial pressure index. In a subgroup of patients with a
      baseline absolute pain-free interval of greater than 500 m, isradipine (n = 6)
      significantly (P less than 0.001) increased both the absolute and the relative
      pain-free intervals and increased the ankle--arm arterial pressure index compared
      with placebo (n = 7). The favourable effects of long-term isradipine treatment
      suggest that isradipine could positively interfere with factors involved in the
      progression of atherosclerotic lesions or improve collateral vessel flow.

PMID- 1387370
TI  - Expression of natriuretic peptide genes in cardiac tissues of hypertensive rats.
AB  - A quantitative assay using a reverse transcriptase-linked polymerase chain
      reaction has been developed for measuring the levels of rANP and iso-rANP mRNA. A
      linear correlation between total RNA template and amplified cDNA was obtained for
      the amplification of cDNA from both iso-rANP and rANP mRNAs even when both cDNAs
      were amplified in the same assay. Application of the assay showed that in
      contrast to rANP levels of iso-rANP transcript in hypertensive rats remained
      approximately the same in atrium but were increased 10-fold in ventricle compared
      to normal rats. Given the relative size of the ventricle the increase of iso-rANP
      in this tissue in SHR may be a major response to the hypertensive state.

PMID- 1387371
TI  - Postnatal ontogenesis of vasopressin receptors in the rat collecting duct.
AB  - The ontogenesis of vasopressin receptors in the rat collecting duct was studied
      by measuring the binding of [1-(beta-mercapto-beta,beta
      cyclopentamethylenepropionic acid),2-O-methyltyrosine,4-threonine,8-ornithine,9
      125I-tyrosylamide+ ++]-vasotocin (125I-d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH(9)2]-OVT) to
      isolated cortical collecting ducts (CCD), outer medullary collecting ducts (OMCD)
      and inner medullary collecting ducts (IMCD) microdissected from collagenase
      treated kidneys of 2- to 34-day-old rats and adult animals. The stereospecificity
      for recognition of a series of seven vasopressin structural analogues by CCD and
      OMCD receptors reveals that the labeled binding sites identified in 11- to 16-day
      old and adult rats are homologous respectively and contain a major population of
      V2 type and a minor population of V1a type of vasopressin receptors. At all
      postnatal stages examined, the receptor density (expressed as 10(-18) mol
      radioligand bound per square millimeter tubular outer surface area) decreases
      gradually from the CCD to the IMCD. For the three segments, the numbers of
      receptors detected remained constant during the first 2 weeks after birth and
      increased sharply after 20 days to reach the corresponding adult levels during
      the fifth week.

PMID- 1387372
TI  - Fractures caused by falling from a wheelchair in patients with neuromuscular
      disease.
AB  - This report discusses the occurrence of fractures caused by falling from a
      wheelchair. 13 distal femur, two proximal humerus and three distal tibia
      fractures were seen in 13 patients, of whom 11 had Duchenne muscular dystrophy,
      one had Becker muscular dystrophy and one had spinal muscular atrophy. All were
      non-ambulant and had been wheelchair-dependent for at least one year before the
      fall occurred. Six patients sustained fractures between 1976 and 1982, and five
      more between 1983 and 1985. Eight subsequent fractures from wheelchair falls have
      occurred since 1986. Although wheelchair design, controls and adaptations have
      continued to improve, wheelchair safety has not.

PMID- 1387373
TI  - Type 1 (insulin-dependent) diabetes mellitus and nitric oxide.

PMID- 1387374
TI  - Suppression of sympathetic nervous system activity by nicorandil during exercise.
AB  - 1. Treadmill testing was done and plasma epinephrine and norepinephrine were
      measured during exercise and recovery in 21 patients with coronary artery disease
      given nicorandil. 2. Epinephrine levels during exercise did not change
      significantly with nicorandil, but the percent change in epinephrine with
      nicorandil tended to be lower during exercise. 3. Norepinephrine levels after
      exercise were suppressed with nicorandil (with, 424 +/- 15 pg/ml; without, 760 +/
      16, P less than 0.05). 4. Also, the percent change in norepinephrine with
      nicorandil was significantly decreased during exercise and recovery (with, 259 +/
      11%; without, 555 +/- 19, P less than 0.01). 5. Therefore, nicorandil suppressed
      the sympathetic nervous system hyper-response to exercise.

PMID- 1387375
TI  - Long-term effects of imipramine on striatal dopamine autoreceptor function:
      involvement of both noradrenergic and serotonergic systems.
AB  - 1. The effects of apomorphine (APO) administration on DA system activity were
      assessed by measuring dopamine metabolite levels (HVA) in several circumstances.
      2. Pretreatment with IMI reduced the effect of APO on HVA levels. 3.
      Pretreatments with either IDE or DMI did not reduce the effect of APO on HVA
      levels. 4. Reductions of either NE and 5-HT levels after DSP4 and pCPA restored
      the effect of APO after IMI pretreatment.

PMID- 1387377
TI  - Sequence of the Bacillus subtilis homolog of the Escherichia coli cell-division
      gene murG.
AB  - The Bacillus subtilis homology of the Escherichia coli murG gene [encoding UDP-N
      acetylglucosamine:N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol N
      acetylglucosamine transferase] was cloned in E. coli K-12 and sequenced. The murG
      homolog encodes a protein of M(r) 39,936 [363 amino acid (aa) residues] of which
      108 aa residues (29.8%) are identical with the E. coli murG product.

PMID- 1387376
TI  - Characterization of dopamine receptors involved in apomorphine-induced pecking in
      pigeons.
AB  - 1. The possible involvement of subtypes of dopamine-receptors in apomorphine
      induced pecking was studied in pigeons. Different doses of apomorphine induced
      pecking in pigeons which was dose-dependent. 2. The response was decreased by SCH
      23390 (D-1 antagonist) or high doses of sulpiride (D-2 antagonist) pretreatment,
      but increased by lower doses of sulpiride. 3. Combination of SCH 23390 with
      sulpiride completely antagonized the apomorphine effect. 4. Single dose
      administration of SKF 38393 (D-1 agonist) or bromocriptine (D-2 agonist) and
      combination of these drugs did not induce pecking, although either SK 23390 or
      bromocriptine increased the apomorphine-induced pecking which was decreased by
      SCH 23390 or sulpiride pretreatment. 5. It may be concluded that pecking, induced
      by apomorphine in pigeons, is elicited through activation of both D-1 and D-2
      dopamine-receptors.

PMID- 1387378
TI  - Chimeric HU-IHF proteins that alter DNA-binding ability.
AB  - Chimeric proteins between Escherichia coli histone-like HU and IHF were
      constructed by genetic engineering, in which part of the arm region was replaced
      by the corresponding region of IHF alpha (designated as HupANhimA) or IHF beta
      (HupANhimD); alternatively, an alpha-helix 2-beta 1 region was replaced by the
      corresponding region of IHF alpha (HupAXhimA) or IHF beta (HupAXhimD) (symbols N
      and X indicate NotI and XhoI junctions). These proteins were synthesized in a
      hupA-hupB double-deletion mutant. HupANhimA exhibited marked reduction in
      nonspecific DNA binding in vitro, and a drastic loss of HU activity in
      replicative transposition of Mu phage in vivo. HupANhimD also showed a
      significant reduction in the ability for DNA binding, though this protein
      supported Mu phage development. In contrast, the other two chimeric HU proteins
      showed only slight changes in nonspecific DNA-binding ability: they retained
      activities for transposition of Mu phage in vivo. These observations confirm that
      the flexible arm of HU-2, a domain proposed for DNA binding [Tanaka et al.,
      Nature 310 (1984) 376-381; Goshima et al., Gene 96 (1990) 141-145], plays an
      important role in the physiological function of this protein. The results
      indicate that a unique conformation of the arm structure of HU protein,
      particularly the N-terminal half of a two-strand antiparallel beta-ribbon of the
      structure, is important for the DNA-binding ability of this protein.

PMID- 1387380
TI  - Medical management of iliocostal pain.

PMID- 1387381
TI  - Curative treatment approaches for esophageal cancer.

PMID- 1387379
TI  - Overproduction of a human snRNP-associated Sm-D autoantigen in Escherichia coli
      and Saccharomyces cerevisiae.
AB  - To conduct functional and autoimmunity studies, we overproduced human Sm-D1 (hSm
      D1), a small nuclear ribonucleoprotein 'core' protein and autoantigen, in
      Escherichia coli and Saccharomyces cerevisiae. Optimal expression in these
      organisms was achieved by designing vectors that synthesized abundant hSm-D1 mRNA
      under the control of the strong, regulatable promoters: T7 phi 10 (E. coli) and
      GAL1 (yeast). In addition, efficient translation initiation of the hSm-D1 coding
      sequence was effected in E. coli by utilizing a two-cistron approach; for
      expression in yeast, we created a 5' untranslated leader whose sequence was based
      on the consensus of highly expressed genes in S. cerevisiae. The hSm-D1 protein
      accumulated at high levels in both bacteria and yeast, representing,
      respectively, approx. 10% and 7% of the total protein. However, in comparison
      with the authentic protein, the recombinant hSm-D1 displayed different
      immunoreactive determinants as assessed by Western blot. We thus conclude that
      certain hSm-D1 immunologic properties are most likely dependent on
      posttranslational modifications that take place in the cells of higher
      eukaryotes.

PMID- 1387382
TI  - [Basic results and perspectives of health studies in the hot climate of
      Uzbekistan].

PMID- 1387383
TI  - [From public health to social medicine].

PMID- 1387384
TI  - [The 7th Congress of Public Health Physicians of Russia: new and old problems].

PMID- 1387385
TI  - [Effects of phospholipid layer on the dynamic microstructure of phosphorylation
      domain of Ca(2+)-ATPase from sarcoplasmic reticulum prepared from rabbit skeletal
      muscle].
AB  - The effects of phospholipids bilayers imposed on the intramolecular dynamic
      microstructure of Ca(2+)-ATPase from rabbit skeletal muscle sarcoplasmic
      reticulum were studied with a nanosecond time-resolved fluorometer. Ca(2+)-ATPase
      was purified and reconstituted into vesicle membranes. The phosphorylation domain
      of Ca(2+)-ATPase was labeled with a fluorophore, N-(1-anilinonaphthyl-4)
      maleimide (ANM). The phospholipids surrounding the hydrophobic segment of Ca(2+)
      ATPase were exchanged with phosphatidylcholines of shorter acyl chain length by
      lipid titration. The membrane viscosity was measured by fluorometry using 1, 6
      diphenyl-1, 3, 5-hexatriene (DPH). The membrane viscosity decreased when the
      intrinsic phospholipids were titrated with phosphatidylcholine having shorter
      acyl chains, and accompanied with a concurrent decrease in Ca(2+)-ATPase
      activity. The replacement of native lipids caused an increase in the fluorescence
      wavelength of ANM-labeled Ca(2+)-ATPase vesicles (red shift). This result
      suggests a conformational change in which the phosphorylation domain becomes more
      hydrophilic. The anisotropy decay time was was analyzed as two components, the
      slower being attributed to the intramolecular oscillation of the phosphorylation
      domain. The half-decay time of ANM fluorescence anisotropy was 72 +/- 4 nsec in
      the control vesicles, 69 +/- 3 nsec in di (18: 1) PC, 61 +/- 4 nsec in di (16: 1)
      PC, 54 +/- 3 nsec in di (14: 1) PC, and 49 +/- 2 nsec in di (12: 0) PC-titrated
      vesicles. This result suggests that the submolecular oscillation of the
      phosphorylation domain of Ca(2+)-ATPase is limited by the physical properties of
      boundary phospholipids, and that changes in the phospholipids cause alterations
      in the molecular motion of this domain, destabilize Ca(2+)-ATPase and reduce its
      activity.

PMID- 1387386
TI  - Autocrine inhibition of mitotic activity in cultured oligodendrocyte-type-2
      astrocyte (O-2A) precursor cells.
AB  - During development, oligodendrocytes are generated from a bipotential glial stem
      cell, the oligodendrocyte-type-2 astrocyte precursor (O-2A). O-2A cells are under
      the mitogenic influence of the platelet-derived growth factor (PDGF) released
      from type-1 astrocytes. In vitro experiments have shown that O-2A cells
      stimulated by PDGF are limited to a set number of divisions and then
      differentiate to oligodendrocytes by becoming unresponsive to the growth factor.
      In the healthy adult central nervous system, oligodendrocyte proliferation
      remains generally quiescent and is possibly under negative growth control. The
      view that O-2A lineage cells are capable of negatively regulating their own
      proliferation is supported by the demonstration that conditioned medium obtained
      from O-2A cultures inhibits their DNA synthesis. In addition to O-2A cells, the
      newly established CG4 cell line, a derivative of O-2A cells, was found to inhibit
      O-2A lineage cell proliferation. The antiproliferative activity was present in
      the media conditioned by CG4 cells that were expanded as undifferentiated O-2A
      precursors, as well as by CG4 cells induced to differentiate to nonproliferating
      oligodendrocytes. Moreover, the inhibitory activity was produced by CG4 cells
      (source cells) propagated by various mitogens. The inhibition of mitotic activity
      was nearly complete, dose-dependent, fully reversible, and exhibited when CG4
      cells (test cells) were stimulated to divide by various mitogens, such as PDGF,
      basic fibroblast growth factor, or medium conditioned by the neuronal B104 cell
      line. The inhibition of proliferation was accompanied by the conversion of the
      phenotype of CG4 cells, from A2B5+/O4- precursors to A2B5-/O4+ pro
      oligodendrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387387
TI  - Characteristics of fish glial cells in culture: possible implications as to their
      lineage.
AB  - Regeneration of injured central nervous system axons is largely dependent on the
      response of the associated nonneuronal glial cells to injury. Glial cells of the
      mammalian central nervous system, unlike those of fish, are apparently not
      conducive to axonal regeneration. While the lineage of rat glial cells is well
      characterized and its role in the support or inhibition of regenerative growth is
      beginning to be understood, little is known about fish glial cells. Accordingly,
      glial cells in cultures of adult goldfish brain and of newly hatched goldfish
      larvae were studied in an attempt to establish their lineage. The cells were
      identified by means of indirect immunofluorescence, using antibodies against fish
      astrocytes and oligodendrocytes. The cell count in the cultures increased from a
      small number of cells at 24 h after plating to a large number of both astrocytes
      and oligodendrocytes after 1 week in culture. Both of these cell types had
      originated from proliferating cells, as shown by their uptake of tritiated
      thymidine and by the inhibition of cell proliferation by 5-fluoro-2'
      deoxyuridine. Both astrocytes, i.e., glial fibrillary acidic protein-positive
      cells, and oligodendrocytes, i.e., 6D2-positive cells, were positively labeled
      also by A2B5 antibodies, which are known to label progenitors of type-2
      astrocytes and oligodendrocytes in the rat optic nerve. The results suggest that
      A2B5 positive progenitor cells in the goldfish central nervous system, as in the
      rat optic nerve, might be a common progenitor of astrocytes and oligodendrocytes.

PMID- 1387388
TI  - Response of microglial cells to experimental rat glioma.
AB  - The response of indigenous CNS microglia to an experimentally induced glioma has
      been studied in rat brain using lectin histochemistry with the Griffonia
      simplicifolia B4-isolectin. The study was undertaken 2 weeks after tumor cell
      injection when tumor size was near maximal. Reactive microglial cells formed a
      dense band that surrounded most of the well-circumscribed tumor mass, and
      extended along the corpus callosum into the contralateral cerebral hemisphere.
      From the periphery inward, reactive microglia extended into the tumor tissue,
      where large numbers of them were found to be present as microglia-derived
      macrophages. The lectin stain, which also labels endothelial cells, revealed a
      highly vascularized tumor with ongoing neovascularization apparent as vascular
      sprouts. Moderate numbers of lectin-stained blood monocytes were localized
      primarily inside the vessel lumina. Our results show that microglial cells react
      to brain tumors; however, it remains to be determined whether the microglial
      response represents an active antitumor defense mechanism that could be
      manipulated during immunotherapeutic approaches.

PMID- 1387390
TI  - The effect of liver macrophages on in vitro cytolytic activity of 5FU and FUdR on
      colon carcinoma cells: evidence of macrophage activation.
AB  - While investigating the effects of 5-fluorouracil (5FU) and 5-fluoro-2'
      deoxyuridine (FUdR) on the tumoricidal state of rat liver macrophages activated
      in vitro by means of liposome-encapsulated muramyl dipeptide (MDP), we observed
      that 5FU in combination with macrophages produced substantially higher extents of
      cytolytic activity on tumor cells than 5FU alone. In contrast, FUdR failed to
      produce this effect; rather, at relatively low FUdR concentrations, lytic
      activity in the presence of macrophages was even significantly diminished as
      compared with FUdR in the absence of macrophages. Both 5FU and FUdR were able to
      enhance the cytolytic activity of macrophages activated by liposome-encapsulated
      MDP. This finding indicates that, rather than inhibiting the activation of
      macrophages by liposomal MDP, 5FU can act as a stimulator of macrophage
      activation by itself. This is further supported by the observations that (i) in
      combination with 5FU, the secretion of TNF induced by liposomal MDP was
      synergistically enhanced and (ii) that a second treatment of macrophages with the
      drug, 24 h after the first, fails to produce increased macrophage cytotoxicity.
      Our results also show that neither 5FU nor FUdR are likely to unfavorably
      influence the induction of cytotoxic activity of the macrophages. Rather,
      combinations of 5FU or FUdR and liposomal MDP may result in an additive or
      synergistic tumoricidal effect.

PMID- 1387389
TI  - CD4+ TCR alpha beta+ T-cell clones derived shortly after allogeneic bone marrow
      transplantation: theophyllamine and verapamil inhibit proliferation of
      functionally heterogeneous T-cells.
AB  - CD4+ TCR alpha beta+ T-cell clones were prepared from three CML-patients 4-6
      weeks after allogeneic bone marrow transplantation and the effects of
      theophyllamine and verapamil on clonal growth then assessed. Both drugs inhibited
      PHA-stimulated autocrine proliferation of clones as well as proliferation of
      clones dependent on exogenous growth factors. Inhibition was seen when using
      different accessory cells (PBM or BCL) during T-cell activation, and both for IL2
      and IL4-dependent proliferation of previously activated T-cells. The isomer R
      verapamil inhibited PHA-stimulated proliferation as well as IL2- and IL4
      dependent T-cell proliferation. The drugs also inhibited proliferation of CD8+ T
      cells. Although the T-cell clones were functionally heterogeneous and were
      derived from different patients and priming cultures, both drugs inhibited all
      clones investigated. However, the degree of inhibition varied between different
      clones.

PMID- 1387392
TI  - Inhibition of proliferation and differentiation of human B-lymphocytes by a
      biscoclaurine alkaloid.
AB  - A biscoclaurine alkaloid, cepharanthine, is known to be a potent inhibitor of
      snake venom-induced hemolysis by interaction with the lipid bilayer of the
      membrane. The drug also interferes with the ion channel intracellularly. In this
      study, we examined the effect of cepharanthine on human B-cell functions. Small
      dense B-cells from tonsil samples were isolated using a Percoll density gradient
      from non-rosetted cells and were used as the target cells. Cepharanthine
      inhibited the proliferation of the lymphocytes and antibody production of human B
      lymphocytes. The inhibitory effect of cepharanthine on the proliferation was
      caused by the arrest of the late G1 to S phase transition in the cell cycle.
      However, the mechanism of suppression of antibody formation remains unknown.
      These results suggest that cepharanthine acts on human B-cells as an
      immunomodulating agent.

PMID- 1387391
TI  - An in vivo model for the experimental selection of drugs able to prevent immune
      complex glomerulonephritis.
AB  - Polyclonal activation of lymphocytes and immune complex-mediated glomerular
      lesions were induced in C57Bl/6 mice by injecting bacterial lipopolysaccharide
      (LPS) twice a week for 2 weeks. The usefulness of such a model for in vivo
      evaluation of immunomodulatory and therapeutic effects of drugs, was investigated
      by treating mice with DIAM4, a cyclophosphazenic compound known to modulate
      polyclonal activation of lymphocytes and to prevent mouse lupus nephritis.
      Prevention of LPS-triggered lymphocyte polyclonal activation and glomerular
      lesions was observed in the DIAM4-treated mice. Such a model can be used
      conveniently to select compounds effective in the treatment of immune
      glomerulonephritis.

PMID- 1387393
TI  - Follicular mucinosis associated with pregnancy.

PMID- 1387394
TI  - A meta-analytic comparison of the effectiveness of smoking cessation methods.
AB  - Meta-analysis was used to cumulate the results from 633 studies of smoking
      cessation, involving 71,806 subjects, that reported the proportion of successful
      quits. Self-care methods do not appear to be as effective as formal intervention
      methods. Instructional programs involving physicians were not more effective than
      other instructional programs. Conditioning-based techniques such as aversive
      methods had success rates similar to those of instructional methods, and among
      the instructional methods, those incorporating social norms and values were more
      successful than those relying solely on didactic approaches. Cumulation of quit
      rates from all available control groups indicated that, on average, 6.4% of the
      smokers could be expected to quit smoking without any intervention. This figure
      must be subtracted from the raw success rate to obtain the net success rate for
      each program. Directions for future research are discussed.

PMID- 1387395
TI  - Mechanism of Streptococcus mutans glucosyltransferases: hybrid-enzyme analysis.
AB  - Streptococcus mutans GS5 expresses three glucosyltransferases (GTFs): GTF-I and
      GTF-SI, which synthesize water-insoluble glucans in a primer-independent manner,
      and GTF-S, which is responsible for the formation of primer-dependent soluble
      glucan. The amino acid sequences of the GTF-I and GTF-S enzymes exhibit
      approximately 50% sequence identity. Various hybrid genes were constructed from
      the structural genes for the enzymes, and their products were analyzed. Three
      different approaches were used to construct the hybrid enzymes: (i) ligation of
      DNA fragments containing compatible endonuclease restriction sites of the two
      genes at homologous positions; (ii) in vivo recombination between the homologous
      regions of each gene; and (iii) random fusion of DNA fragments from each gene
      generated following exonuclease III digestion of tandemly arranged fragments
      corresponding to the two functional domains of each enzyme. Hybrid GTFs composed
      of the sucrose-binding domain of one enzyme (GTF-I or GTF-S) with the glucan
      binding domain of the other synthesized insoluble glucan exclusively in the
      absence of primer dextran. Insoluble glucan synthesis by some, but not all, of
      the GTF-S:GTF-I chimeric enzymes was stimulated by primer dextran T10 addition.
      In addition, glucan binding by the former but not latter group of hybrid GTFs was
      demonstrated. These results suggest that the glucan-binding domain alone does not
      solely determine primer dependence or independence or the structure of the
      resulting glucan product, although this carboxyl-terminal domain containing
      direct repeating units does appear to play a significant role in primer
      dependence.

PMID- 1387396
TI  - Inhibition of actin-tropomyosin activation of myosin MgATPase activity by the
      smooth muscle regulatory protein caldesmon.
AB  - Caldesmon inhibition of actin-tropomyosin activation of myosin MgATPase activity
      was investigated. greater than 90% inhibition of ATPase activation correlated
      with 0.035-0.1 caldesmon bound per actin monomer over a wide range of conditions.
      Caldesmon inhibited sheep aorta actin-tropomyosin activation of skeletal muscle
      heavy meromyosin (HMM) by 85%, but had no effect on the binding affinity of
      HMM.ADP.Pi to actin. At ratios of 2 and 0.12 subfragment 1 (S1):1 actin, addition
      of caldesmon inhibited the ATPase activation by up to 95%, but did not alter the
      fraction of S1.ADP.Pi associated with actin-tropomyosin. We concluded that
      caldesmon inhibited actomyosin ATPase by slowing the rate-limiting step of the
      activation pathway. At concentrations comparable to the ATPase measurements, S1
      displaced caldesmon from native thin filaments both in the absence (rigor) and
      the presence of MgATP. We therefore concluded that caldesmon could displace
      S1.ADP.Pi from actin-tropomyosin only under exceptional circumstances. An
      expressed mutant of caldesmon comprising just the C-terminal 99 amino acids bound
      actin 10 times weaker than whole caldesmon but otherwise inhibited actin
      tropomyosin activation with the same potency and same mechanism as intact
      caldesmon. Thus, the entire inhibitory function of caldesmon resides in its
      extreme C terminus.

PMID- 1387397
TI  - In vivo conversion of [3H]myoinositol to [3H]chiroinositol in rat tissues.
AB  - We report here the in vivo conversion of [3H]myoinositol to [3H]chiroinositol.
      After labeling intraperitoneally with [3H]myoinositol for 3 days to reach
      radioisotope equilibrium in urine, [3H]chiroinositol was isolated from tissues
      and purified after 6 N HCl hydrolysis by two sequential paper chromatographies
      and high performance liquid chromatography (HPLC). Percent conversion of
      [3H]myoinositol to [3H]chiroinositol was highest in urine (36%), liver (8.8%),
      muscle (8.8%), and blood (7.6%) with intestine, brain, kidney, spleen, and heart
      decreasing in percentage from 2.8 to 0.7%. Labeling of other inositol isomers
      including scyllo-, neo-, and epi-, and mucoinositol was minimal, approximately
      0.06% of [3H]myoinositol. Glucose was unlabeled, but glucuronate, the product of
      myoinositol oxidation, was labeled up to 1.5% of the [3H] myoinositol. Acid
      hydrolysates of combined inositol-containing phospholipids contain significant
      labeled chiroinositol. [3H]Phosphatidylinositols and
      [3H]glycosylphosphatidylinositols were extracted from liver, muscle, and blood,
      isolated by thin layer chromatography, and inositols purified by HPLC after acid
      hydrolysis. Percent conversion of [3H]myoinositol to [3H] chiroinositol was
      highest in blood (60.4%) followed by muscle (7.7%) and liver (2.2%).

PMID- 1387398
TI  - Fluoride binding to the calcium ATPase of sarcoplasmic reticulum converts its
      transport sites to a low affinity, lumen-facing form.
AB  - The sarcoplasmic reticulum CaATPase forms an inactive complex with fluoride
      (CaATPase-F), which in the absence of calcium reactivates very slowly (t1/2
      approximately 40 h at 25 degrees C). Reactivation is greatly accelerated (greater
      than 10(3)) by calcium in the millimolar range provided it has access to luminal
      sites of the enzyme. Measurement of the calcium concentration dependence of the
      reactivation rate constant revealed a saturable effect with a midpoint of about
      12 mM calcium. These results show that an effect other than phosphorylation can
      produce a greater than 10(3)-fold affinity decrease and reorientation of the
      calcium transport sites. At a fixed calcium concentration, reactivation became
      faster with increasing pH (pKa greater than 8), suggesting competition between
      Ca2+ and H+ for transport sites. CaATPase-F lacked the ability to bind calcium
      with high affinity or to form phosphorylated enzyme intermediate from Pi; it
      bound adenyl-5'-yl methylenediphosphonate more than 10-fold less strongly than
      control CaATPase, had numerous sulfhydryl groups with significantly different
      reactivity, and was notably less susceptible (more than 10-fold) to thermal
      inactivation compared with control Ca-ATPase. These results suggest that
      formation of Ca-ATPase-F involves significant structural changes.

PMID- 1387399
TI  - Formation and structure of the C5b-7 complex of the lytic pathway of complement.
AB  - The formation and structure of the complement cytolytic intermediary complex, C5b
      7, were studied with the aim of determining the interactive regions of C5, C6,
      and C7. The structure of human complement component C5 was elucidated by the
      application of limited proteolysis which generated well characterized major
      polypeptide fragments of this molecule. Plasmin, thrombin, and kallikrein cleave
      C5b with greater facility than C5. The most useful cleavage of C5b was effected
      by plasmin because the fragmentation pattern was similar to the processing of C3b
      by factors H, I, and kallikrein. Plasmin hydrolyzes peptide bonds within the
      alpha'-chain of C5b, resulting in a four-chain fragment, C5c (M(r) = 142,000),
      and a single chain fragment, C5d (M(r) = 43,000). Circular dichroism
      spectroscopic analyses indicated that C5d is substantially richer in alpha
      helical content than is C5c (27 versus 9%). Polyclonal antibodies directed
      against C5c blocked the interaction of C5b-6 with C7, whereas antibodies directed
      against C5d inhibited the binding of C5 with C3b. Chemical cross-linking using a
      cleavable radioiodinated photoreactive reagent revealed that both C6 and C7
      associate preferentially with the alpha'-chain of C5b. The reversible
      interactions of C5 with C6, C7, and major polypeptide fragments derived from
      these were investigated with solid phase binding assays. The results indicate
      that the carboxyl-terminal domains of C6 and C7, which have cysteine-rich modules
      homologous to those found in factors H and I, have the capacity to link
      specifically with C5.

PMID- 1387400
TI  - Control of microtubule dynamics and length by cyclin A- and cyclin B-dependent
      kinases in Xenopus egg extracts.
AB  - In eukaryotic cells, the onset of mitosis involves cyclin molecules which
      interact with proteins of the cdc2 family to produce active kinases. In
      vertebrate cells, cyclin A dependent kinases become active in S- and pro-phases,
      whereas a cyclin B-dependent kinase is mostly active in metaphase. It has
      recently been shown that, when added to Xenopus egg extracts, bacterially
      produced A- and B-type cyclins associate predominantly with the same kinase
      catalytic subunit, namely p34cdc2, and induce its histone H1 kinase activity with
      different kinetics. Here, we show that in the same cell free system, both the
      addition of cyclin A and cyclin B changes microtubule behavior. However, the
      cyclin A-dependent kinase does not induce a dramatic shortening of centrosome
      nucleated microtubules whereas the cyclin B-dependent kinase does, as previously
      reported. Analysis of the parameters of microtubule dynamics by fluorescence
      video microscopy shows that the dramatic shortening induced by the cyclin B
      dependent kinase is correlated with a several fold increase in catastrophe
      frequency, an effect not observed with the cyclin A-dependent kinase. Using a
      simple mathematical model, we show how the length distributions of centrosome
      nucleated microtubules relate to the four parameters that describe microtubule
      dynamics. These four parameters define a threshold between unlimited microtubule
      growth and the establishment of steady-state dynamics, which implies that well
      defined steady-state length distributions can be produced by regulating precisely
      the respective values of the dynamical parameters. Moreover, the dynamical model
      predicts that increasing catastrophe frequency is more efficient than decreasing
      the rescue frequency to reduce the average steady state length of microtubules.
      These theoretical results are quantitatively confirmed by the experimental data.

PMID- 1387401
TI  - Cyclin A potentiates maturation-promoting factor activation in the early Xenopus
      embryo via inhibition of the tyrosine kinase that phosphorylates cdc2.
AB  - We have produced human cyclin A in Escherichia coli and investigated how it
      generates H1 kistone kinase activity when added to cyclin-free extracts prepared
      from parthenogenetically activated Xenopus eggs. Cyclin A was found to form a
      major complex with cdc2, and to bind cdk2/Eg1 only poorly. No lag phase was
      detected between the time when cyclin A was added and the time when H1 histone
      kinase activity was produced in frog extracts, even in the presence of 2 mM
      vanadate, which blocks cdc25 activity. Essentially identical results were
      obtained using extracts prepared from starfish oocytes. We conclude that
      formation of an active cyclin A-cdc2 kinase during early development escapes an
      inhibitory mechanism that delays formation of an active cyclin B-cdc2 kinase.
      This inhibitory mechanism involves phosphorylation of cdc2 on tyrosine 15.
      Okadaic acid (OA) activated cyclin B-cdc2 kinase and strongly reduced tyrosine
      phosphorylation of cyclin B-associated cdc2, even in the presence of vanadate. 6
      dimethylamino-purine, a reported inhibitor of serine-threonine kinases,
      suppressed OA-dependent activation of cyclin B-cdc2 complexes. This indicates
      that the kinase(s) which phosphorylate(s) cdc2 on inhibitory sites can be
      inactivated by a phosphorylation event, itself antagonized by an OA-sensitive,
      most likely type 2A phosphatase. We also found that cyclin B- or cyclin A-cdc2
      kinases can induce or accelerate conversion of the cyclin B-cdc2 complex from an
      inactive into an active kinase. Cyclin B-associated cdc2 does not undergo
      detectable phosphorylation on tyrosine in egg extracts containing active cyclin A
      cdc2 kinase, even in the presence of vanadate. We propose that the active cyclin
      A-cdc2 kinase generated without a lag phase from neo-synthesized cyclin A and
      cdc2 may cause a rapid switch in the equilibrium of cyclin B-cdc2 complexes to
      the tyrosine-dephosphorylated and active form of cdc2 during early development,
      owing to strong inhibition of the cdc2-specific tyrosine kinase(s). This may
      explain why early cell cycles are so rapid in many species.

PMID- 1387402
TI  - Homology of the 74-kD cytoplasmic dynein subunit with a flagellar dynein
      polypeptide suggests an intracellular targeting function.
AB  - In previous work we found cytoplasmic dynein to be a complex of two catalytic
      heavy chains and at least seven co-purifying polypeptides of unknown function.
      The most prominent of these is a 74-kD electrophoretic species which can be
      resolved as two to three bands by SDS-PAGE. We have now selected a series of
      overlapping rat brain cDNAs encoding the 74-kD species. The deduced sequence of a
      full-length cDNA predicts a 72,753 D polypeptide which includes the amino acid
      sequences of nine peptides determined by NH2-terminal microsequencing. PCR
      performed on first strand rat brain cDNA together with the sequence of a
      partially matching tryptic peptide indicated the existence of at least three
      isoforms of the 74-kD cytoplasmic dynein subunit. Comparison with known sequences
      revealed that the carboxyl-terminal half of the polypeptide is 26.4% identical
      and 47.7% similar to the product of the Chlamydomonas ODA6 gene, a 70-kD
      intermediate chain of flagellar outer arm dynein. Immunoblot analysis with a
      monoclonal antibody to the 74-kD species indicated a widespread tissue
      distribution, as expected for a cytoplasmic dynein subunit. Nonetheless, the
      antibody recognized a 67-kD species in ram sperm flagella and pig tracheal cilia,
      supporting the existence of distinct but related cytoplasmic and axonemal
      polypeptides in mammals. In view of evidence for a role for the ODA6 gene product
      in anchoring flagellar dynein to the A subfiber microtubule in the axoneme, we
      predict an analogous role for the 74-kD polypeptide, perhaps in mediating the
      interaction of cytoplasmic dynein with membranous organelles and kinetochores.

PMID- 1387403
TI  - Arrangement of inner dynein arms in wild-type and mutant flagella of
      Chlamydomonas.
AB  - We have used computer averaging of electron micrographs from longitudinal and
      cross-sections of wild-type and mutant axonemes to determine the arrangement of
      the inner dynein arms in Chlamydomonas reinhardtii. Based on biochemical and
      morphological data, the inner arms have previously been described as consisting
      of three distinct subspecies, I1, I2, and I3. Our longitudinal averages revealed
      10 distinguishable lobes of density per 96-nm repeating unit in the inner row of
      dynein arms. These lobes occurred predominantly but not exclusively in two
      parallel rows. We have analyzed mutant strains that are missing I1 and I2
      subspecies. Cross-sectional averages of pf9 axonemes, which are missing the I1
      subspecies, showed a loss of density in both the inner and outer portions of the
      inner arm. Averages from longitudinal images showed that three distinct lobes
      were missing from a single region; two of the lobes were near the outer arms but
      one was more inward. Serial 24-nm cross-sections of pf9 axonemes showed a
      complete gap at the proximal end of the repeating unit, confirming that the I1
      subunit spans both inner and outer portions of the inner arm region. Examination
      of pf23 axonemes, which are missing both I1 and I2 subspecies, showed an
      additional loss almost exclusively in the inner portion of the inner arm. In
      longitudinal view, this additional loss occurred in three separate locations and
      consisted of three inwardly placed lobes, one adjacent to each of the two radial
      spokes and the third at the distal end of the repeating unit. These same lobes
      were absent ida4 axonemes, which lack only the I2 subspecies. The I2 subspecies
      thus does not consist of a single dynein arm subunit in the middle of the
      repeating unit. The radial spoke suppressor mutation, pf2, is missing four
      polypeptides of previously unknown location. Averages of these axonemes were
      missing a portion of the structures remaining in pf23 axonemes. This result
      suggests that polypeptides of the radial spoke control system are close to the
      inner dynein arms.

PMID- 1387404
TI  - Extragenic suppressors of paralyzed flagellar mutations in Chlamydomonas
      reinhardtii identify loci that alter the inner dynein arms.
AB  - We have analyzed extragenic suppressors of paralyzed flagella mutations in
      Chlamydomonas reinhardtii in an effort to identify new dynein mutations. A
      temperature-sensitive allele of the PF16 locus was mutagenized and then screened
      for revertants that could swim at the restrictive temperature (Dutcher et al.
      1984. J. Cell Biol. 98:229-236). In backcrosses of one of the revertant strains
      to wild-type, we recovered both the original pf16 mutation and a second, unlinked
      suppressor mutation with its own flagellar phenotype. This mutation has been
      identified by both recombination and complementation tests as a new allele of the
      previously uncharacterized PF9 locus on linkage group XII/XIII. SDS-PAGE analysis
      of isolated flagellar axonemes and dynein extracts has demonstrated that the pf9
      strains are missing four polypeptides that form the I1 inner arm dynein subunit.
      The primary effect of the loss of the I1 subunit is a decrease in the forward
      swimming velocity due to a change in the flagellar waveform. Both the flagellar
      beat frequency and the axonemal ATPase activity are nearly wild-type. Examination
      of axonemes by thin section electron microscopy and image averaging methods
      reveals that a specific domain of the inner arm complex is missing in the pf9
      mutant strains (see accompanying paper by Mastronarde et al.). When combined with
      other flagellar defects, the loss of the I1 subunit has synergistic effects on
      both flagellar assembly and flagellar motility. These synthetic phenotypes
      provide a screen for new suppressor mutations in other loci. Using this approach,
      we have identified the first interactive suppressors of a dynein arm mutation and
      an unusual bypass suppressor mutation.

PMID- 1387405
TI  - The motile beta/IC1 subunit of sea urchin sperm outer arm dynein does not form a
      rigor bond.
AB  - We used in vitro translocation and cosedimentation assays to study the
      microtubule binding properties of sea urchin sperm outer arm dynein and its
      beta/IC1 subunit. Microtubules glided on glass-absorbed sea urchin dynein for a
      period of time directly proportional to the initial MgATP2- concentration and
      then detached when 70-95% of the MgATP2- was hydrolyzed. Detachment resulted from
      MgATP2- depletion, because (a) perfusion with fresh buffer containing MgATP2-
      reconstituted binding and gliding, (b) microtubules glided many minutes with an
      ATP-regenerating system at ATP concentrations which alone supported gliding for
      only 1-2 min, and (c) microtubules detached upon total hydrolysis of ATP by an
      ATP-removal system. The products of ATP hydrolysis antagonized binding and
      gliding; as little as a threefold excess of ADP/Pi over ATP resulted in complete
      loss of microtubule binding and translocation by the beta/IC1 subunit. In
      contrast to the situation with sea urchin dynein, microtubules ceased gliding but
      remained bound to glass-absorbed Tetrahymena outer arm dynein when MgATP2- was
      exhausted. Cosedimentation assays showed that Tetrahymena outer arm dynein
      sedimented with microtubules in an ATP-sensitive manner, as previously reported
      (Porter, M.E., and K. A. Johnson. J. Biol. Chem. 258: 6575-6581). However, the
      beta/IC1 subunit of sea urchin dynein did not cosediment with microtubules in the
      absence of ATP. Thus, this subunit, while capable of generating motility, lacks
      both structural and rigor-type microtubule binding.

PMID- 1387406
TI  - The alpha subunit of sea urchin sperm outer arm dynein mediates structural and
      rigor binding to microtubules.
AB  - Glass-adsorbed intact sea urchin outer arm dynein and its beta/IC1 subunit
      supports movement of microtubules, yet does not form a rigor complex upon
      depletion of ATP (16). We show here that rigor is a feature of the isolated
      intact outer arm, and that this property subfractionates with its alpha heavy
      chain. Intact dynein mediates the formation of ATP-sensitive microtubule bundles,
      as does the purified alpha heavy chain, indicating that both particles are
      capable of binding to microtubules in an ATP-sensitive manner. In contrast, the
      beta/IC1 subunit does not bundle microtubules. Bundles formed with intact dynein
      are composed of ribbon-like sheets of parallel microtubules that are separated by
      54 nm (center-to-center) and display the same longitudinal repeat (24 nm) and
      cross-sectional geometry of dynein arms as do outer doublets in situ. Bundles
      formed by the alpha heavy chain are composed of microtubules with a center-to
      center spacing of 43 nm and display infrequent, fine crossbridges. In contrast to
      the bridges formed by the intact arm, the links formed by the alpha subunit are
      irregularly spaced, suggesting that binding of the alpha heavy chain to the
      microtubules is not cooperative. Cosedimentation studies showed that: (a) some of
      the intact dynein binds in an ATP-dependent manner and some binds in an ATP
      independent manner; (b) the beta/IC1 subunit does not cosediment with
      microtubules under any conditions; and (c) the alpha heavy chain cosediments with
      microtubules in the absence or presence of MgATP2-. These results suggest that
      the structural binding observed in the intact arm also is a property of its alpha
      heavy chain. We conclude that whereas force-generation is a function of the
      beta/IC1 subunit, both structural and ATP-sensitive (rigor) binding of the arm to
      the microtubule are mediated by the alpha subunit.

PMID- 1387408
TI  - A statistical model based fundamental frequency synthesizer for Mandarin speech.
AB  - A novel method based on a statistical model for the fundamental-frequency (F0)
      synthesis in Mandarin text-to-speech is proposed. Specifically, a statistical
      model is employed to determine the relationship between F0 contour patterns of
      syllables and linguistic features representing the context. Parameters of the
      model were empirically estimated from a large training set of sentential
      utterances. Phonologic rules are then automatically deduced through the training
      process and implicitly memorized in the model. In the synthesis process,
      contextual features are extracted from a given input text, and the best estimates
      of F0 contour patterns of syllable are then found by a Viterbi algorithm using
      the well-trained model. This method can be regarded as employing a stochastic
      grammar to reduce the number of candidates of F0 contour pattern at each decision
      point of synthesis. Although linguistic features on various levels of input text
      can be incorporated into the model, only some relevant contextual features
      extracted from neighboring syllables were used in this study. Performance of this
      method was examined by simulation using a database composed of nine repetitions
      of 112 declarative sentential utterances of the same text, all spoken by a single
      speaker. By closely examining the well-trained model, some evidence was found to
      show that the declination effect as well as several sandhi rules are implicitly
      contained in the model. Experimental results show that 77.56% of synthesized F0
      contours coincide with the VQ-quantized counterpart of the original natural
      speech. Naturalness of the synthesized speech was confirmed by an informal
      listening test.

PMID- 1387409
TI  - Balloon angioplasty of native aortic coarctation.

PMID- 1387407
TI  - Analysis of a developmentally regulated nuclear localization signal in Xenopus.
AB  - The 289 residue nuclear oncoprotein encoded by the adenovirus 5 Ela gene contains
      two peptide sequences that behave as nuclear localization signals (NLS). One
      signal, located at the carboxy terminus, is like many other known NLSs in that it
      consists of a short stretch of basic residues (KRPRP) and is constitutively
      active in cells. The second signal resides within an internal 45 residue region
      of E1a that contains few basic residues or sequences that resemble other known
      NLSs. Moreover, this internal signal functions in injected Xenopus oocytes, but
      not in transfected Xenopus A6 cells, suggesting that it could be regulated
      developmentally (Slavicek et al. 1989. J. Virol. 63:4047). In this study, we show
      that the activity of this signal is sensitive to ATP depletion in vivo,
      efficiently directs the import of a 50 kD fusion protein and can compete with the
      E1a carboxy-terminal NLS for nuclear import. In addition, we have delineated the
      precise amino acid residues that comprise the second E1a NLS, and have assessed
      its utilization during Xenopus embryogenesis. Using amino acid deletion and
      substitution analyses, we show that the signal consists of the sequence FV(X)7
      20MXSLXYM(X)4MF. By expressing in Xenopus embryos a truncated E1a protein that
      contains only the second NLS and by monitoring its cytoplasmic/nuclear
      distribution during development with indirect immunofluorescence, we find that
      the second NLS is utilized up to the early neurula stage. In addition, there
      appears to be a hierarchy among the embryonic germ layers as to when the second
      NLS becomes nonfunctional. For this reason, we refer to this NLS as the
      developmentally regulated nuclear localization signal (drNLS). The implications
      of these findings for early development are discussed.

PMID- 1387411
TI  - Estimating the prevalence of long-term disability for an aging society.
AB  - Using information from two national data sets, this report provides projections
      of disability rates for the U.S. population age 65 and above. The research
      develops a series of projections based upon alternative sets of assumptions about
      mortality and disability. Using 1986 baseline disability data, estimates by
      single year of age are projected through the year 2040. The social policy
      implications of these projections are discussed in the final section.

PMID- 1387410
TI  - Effects of aging and dietary restriction on tissue protein synthesis:
      relationship to plasma insulin-like growth factor-1.
AB  - Insulin-like growth factor-1 (IGF-1) decreases with age in many species and
      appears to have an important role in the age-related decline in capacity for
      protein synthesis with age. The goals of these studies were to determine whether
      (a) ad libitum fed mice demonstrate age-related decreases in IGF-1, (b) the
      relationship between IGF-1 and age-related changes in protein synthetic capacity
      in ad libitum fed animals, and (c) whether moderate dietary restriction (which
      increases both life span and protein synthetic capacity) delays age-related
      changes in protein synthesis and plasma IGF-1. These studies indicate that (a) in
      ad libitum fed animals, plasma IGF-1 decreases with age between 10 and 15 months
      and moderate dietary restriction decreases plasma IGF-1 in young but not older
      animals, and (b) the temporal changes in protein synthesis are tissue specific;
      moderate dietary restriction either increases or prevents the age-related decline
      in tissue protein synthesis. Results suggest that in normal aging, decreases in
      IGF-1 are associated with the decline in protein synthesis but that other
      regulatory mechanisms appear to have an important role in this process. Dietary
      restriction decreases plasma IGF-1 in young animals and either increases protein
      synthesis or prevents the age-related decline in protein synthesis, suggesting
      that the effects of dietary restriction are not mediated via increases in plasma
      IGF-1.

PMID- 1387412
TI  - Human dermal fibroblast interleukin-1 receptor antagonist (IL-1ra) and
      interleukin-1 beta (IL-1 beta) mRNA and protein are co-stimulated by phorbol
      ester: implication for a homeostatic mechanism.
AB  - Although the major functions of fibroblasts are to produce extracellular matrix
      and to maintain a structural framework for organ systems, recent studies have
      demonstrated that fibroblasts are active participants in inflammatory processes
      by synthesizing various inflammatory mediators. In this report, we provide
      evidence that fibroblasts may contribute to the regulation of inflammation by the
      synthesis of both the intracellular form and the secretory form of interleukin-1
      receptor antagonists in conjunction with interleukin-1 beta production. Indirect
      immunofluorescence microscopy localized interleukin-1 receptor antagonist and
      interleukin-1 beta proteins primarily in the fibroblast cytoplasm. Polymerase
      chain reaction amplification of reverse-transcribed mRNA with primers specific
      for the intracellular form of interleukin-1 receptor antagonist detected cDNA
      fragments present in both unstimulated and phorbol ester-stimulated fibroblasts,
      identical in molecular size to that in unstimulated keratinocytes. Amplification
      with primers specific for the secretory form of interleukin-1 receptor
      antagonist, however, detected cDNA fragments in phorbol ester-stimulated
      fibroblasts and phytohemagglutinin-stimulated peripheral mononuclear cells, but
      not in unstimulated fibroblasts or keratinocytes. The amplified fibroblast cDNA
      sequences for both intracellular and secretory interleukin-1 receptor antagonists
      were confirmed by digestion with three restriction endonucleases. By ethidium
      bromide visualization of amplified cDNA derived from serially diluted total
      cellular RNA and by Southern blot hybridization analysis of amplified cDNA, we
      have demonstrated that fibroblast interleukin-1 receptor antagonist mRNA and
      interleukin-1 beta mRNA were co-stimulated by phorbol ester. Similarly, ELISA
      demonstrated that fibroblast cytoplasmic interleukin-1 receptor antagonist
      protein and interleukin-1 beta protein were co-stimulated by phorbol ester. Our
      data suggests that the intracellular form of interleukin-1 receptor antagonist
      may be important in maintaining physiologic homeostasis in fibroblasts during
      interleukin-1 beta induction and release.

PMID- 1387413
TI  - Inhibition of lecithin:cholesterol acyltransferase activity by synthetic
      phosphatidylcholine species containing eicosapentaenoic acid or docosahexaenoic
      acid in the sn-2 position.
AB  - Phospholipids isolated from the plasma of monkeys fed a diet enriched in fish oil
      were poor substrates for cholesteryl ester (CE) synthesis by the
      lecithin:cholesterol acyltransferase (LCAT) reaction relative to those from
      animals fed a lard containing diet when the phospholipids were used for the
      preparation of recombinant particles by cholate dialysis (Parks, J. S., B. C.
      Bullock, and L. L. Rudel. 1989. J. Biol. Chem. 264: 2545-2551). The purpose of
      the present study was to directly test the influence of eicosapentaenoic acid
      (20:5 n-3) and docosahexaenoic acid (22:6 n-3) in the sn-2 position of
      phosphatidylcholine (PC) on the activity of LCAT. PC species containing 1
      palmitoyl-2-oleoyl PC (POPC), 1-palmitoyl-2-linoleoyl PC (PLPC), 1-palmitoyl-2
      arachidonoyl PC (PAPC), 1-palmitoyl-2-eicosapentaenoyl PC (PEPC), or 1-palmitoyl
      2-docosahexaenoyl PC (PDPC) were purchased or synthesized and made into
      recombinant particles of uniform size and composition with [14C]cholesterol and
      apoA-I using the cholate dialysis procedure. The recombinant particles
      (PC:cholesterol:apoA-I molar ratio = 42:1.9:1) exhibited the following order of
      reactivity towards purified human LCAT in vitro: POPC greater than PLPC greater
      than PEPC = PAPC greater than PDPC. The apparent Vmax/Km for recombinant
      particles containing PEPC and PDPC was 17% and 7% that of particles containing
      POPC, respectively. There was a linear decrease in CE formation when the
      percentage of PEPC or PDPC was increased from 0 to 100% relative to POPC in
      recombinant particles with a constant PC:cholesterol:apoA-I molar ratio,
      suggesting that the PEPC and PDPC were competitive inhibitors of the LCAT
      reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387414
TI  - Interleukin 1: an important mediator of host resistance against Pneumocystis
      carinii.
AB  - The importance of endogenous interleukin 1 (IL-1) in resistance to Pneumocystis
      carinii infection was examined in a SCID mouse model. Naturally acquired
      pulmonary infection of P. carinii in SCID mice was completely cleared by
      reconstitution of the infected mice with immunocompetent spleen cells. IL-1
      activity in the lung homogenate supernatant of these mice increased significantly
      after reconstitution and returned to baseline level after the clearance of P.
      carinii. Treatment of reconstituted SCID mice with 35F5, a monoclonal antibody
      against murine type I IL-1R almost completely inhibited the clearance of P.
      carinii. In contrast, treatment with control rat immunoglobulin G had no
      detectable effect. Further study revealed that for the complete clearance of P.
      carinii, IL-1 must be present at the early stage of immune responses induced by
      reconstitution, since clearance could be blocked by a single injection of 35F5
      into SCID mice at 2 d, but not at either 8 or 13 d postreconstitution.
      Furthermore, pulmonary recruitment of neutrophils, macrophages, and lymphocytes
      was significantly inhibited in mice that received 35F5 treatment. These findings
      strongly suggest that, in reconstituted SCID mice, endogenous IL-1 is important
      in host resistance to P. carinii infection and that IL-1 may function early in
      the host response possibly by the recruitment of inflammatory cells into the
      lungs.

PMID- 1387415
TI  - A 68-kD GTP-binding protein associated with the T cell receptor complex.
AB  - The identity of the guanine nucleotide-binding protein (G protein) involved in T
      cell activation pathways remains unclear. We identified a 68-kD GTP-binding
      protein associated with the T cell receptor (TCR)/CD3 complex using
      immunoprecipitation and GTP-affinity labeling techniques. Proteins
      coimmunoprecipitated with the TCR/CD3 complex in digitonin lysate of a human
      leukemic T cell line, MOLT 16, were incubated with alpha-[32P]GTP and irradiated
      with ultraviolet rays to covalently link the labeled GTP to GTP-binding proteins.
      They were then analyzed by electrophoresis. The 68-kD protein exhibited
      nucleotide specificity for GTP-binding and was insensitive to cholera and
      pertussis toxins. The 68-kD GTP-binding protein could be coimmunoprecipitated
      with the TCR/CD3 complex but not with other surface molecules such as major
      histocompatibility complex class I and lymphocyte function associated-1, which do
      not cause rapid Ca2+ mobilization. These suggest that the 68-kD GTP-binding
      protein is specifically associated with the TCR/CD3 complex.

PMID- 1387416
TI  - Huntington disease: a detective story.
AB  - As recombinant DNA diagnoses of various inherited diseases become a standard
      medical procedure, the practicing physician will be required to identify families
      at risk and counsel them (or refer them) appropriately. In many families the risk
      may not be immediately obvious or a reliable risk figure may appear to be
      unattainable. In the case presented, the patient had an apparent 50% risk for
      Huntington disease and all the immediate affected relatives were deceased. This
      relatively common scenario would generally prevent recombinant DNA diagnostic
      procedures from arriving at a more accurate risk estimate. Nevertheless, by
      recombinant DNA analysis, a risk for Huntington disease of less than 1% was
      obtained. Several key aspects of genetic analysis were required including
      extensive family histories, identification of informative markers, ordering the
      markers around the disease gene and appropriate statistical analyses. These
      discussions illustrate the power of recombinant DNA techniques to detect genetic
      disorders and demonstrate why they will be of increasing importance to the
      practicing physician.

PMID- 1387417
TI  - Pharmacokinetics of potential anti-AIDS agents thiofoscarnet and foscarnet in the
      cat.
AB  - The pharmacokinetics of thiophosphonoformate (TPFA) and phosphonoformate
      (foscarnet, PFA) were studied in normal adult cats, a species susceptible to
      feline immunodeficiency virus (FIV) infection. Parent drugs and metabolites were
      quantitated by high-performance liquid chromatography (HPLC). TPFA had a mean
      terminal plasma half-life of 42 min, a total clearance of 4.58 ml/min/kg, and a
      renal clearance of 1.24 ml/min/kg (N = 4). TPFA underwent in vivo metabolism to
      PFA and thiophosphonic acid (TPA); the latter was inactive against HIV reverse
      transcriptase. The 6-h cumulative urinary excretion was 42.3% of the intravenous
      administered dose of TPFA, consisting of 23.5% unchanged TPFA, 13.8% PFA, and
      5.0% TPA. In comparison, PFA had a mean (N = 5) terminal half-life of 172 min and
      a total clearance of 1.88 ml/min/kg, approximating its renal clearance. There was
      no evidence of PFA metabolism. Oral doses of TPFA were administered either in
      enteric-coated capsules or in solution by gavage. The mean oral bioavailability
      of encapsulated TPFA and PFA was 22 and 8%, respectively. When given by gavage,
      TPFA had a higher mean bioavailability (33%), but with a greater variability.
      Based on the 6-h cumulative urinary excretion of TPFA, the mean oral
      bioavailability of TPFA was 44%, similar to that based on plasma data. The TPFA
      appears to be superior to PFA because of its greater oral bioavailability and its
      ability to deliver an active metabolite, PFA, to the systemic circulation after
      oral dosing.

PMID- 1387419
TI  - Long-term followup with the use of lyophilized dura mater for abdominal wall
      closure in children: report of 3 cases.
AB  - We report our experience with 3 children treated during infancy by abdominal wall
      reconstruction using lyophilized dura mater. Followup has been 36, 46 and 96
      months postoperatively and they demonstrated adequate abdominal wall healing. One
      child has mild muscular diastasis, while 1 has completely healed. In 1 child a
      small defect developed in the repair, which was closed at a secondary procedure.
      Wound infection, dehiscence or herniation did not occur. There has been no
      evidence of Creutzfeldt-Jakob disease, which has been reported when allogenic
      dura was not obtained from registered tissue banks. Our experience with dura
      mater suggests that the material may be a useful adjunct in the repair and
      closure of complex abdominal defects.

PMID- 1387418
TI  - Physical disability among Canadians reporting musculoskeletal diseases.
AB  - About one million Canadian adults are estimated to have physical disabilities
      attributed to a musculoskeletal condition, a prevalence of 50.1/1,000 adults (all
      rates expressed/1,000). The specific musculoskeletal disease rates were
      arthritis/rheumatism (27.2), back (16.2), "other" (4.6), trauma (3.6) and bone
      (0.6). More women reported disabling musculoskeletal disease (61.0 versus 38.6,
      respectively). Prevalence rates increased with age from 6.2 among Canadians aged
      15-24 years, to 264.7 aged 85 years and over. Limitations of mobility were more
      common than those of agility. Adults in institutions reported more disabilities
      than did adults in households (means 7.7 and 4.4, respectively).

PMID- 1387420
TI  - Laparoscopic treatment of obstructed ureter due to endometriosis by resection and
      ureteroureterostomy: a case report.

PMID- 1387421
TI  - Laparoscopic diverticulectomy: preliminary report of a new approach for the
      treatment of bladder diverticulum.
AB  - Laparoscopic techniques have expanded the possibilities of endo-surgically
      approaching urological abnormalities that would otherwise be managed via an open
      operation. We report on another useful application of the laparoscope, bladder
      diverticulectomy. A large bladder diverticulum, responsible for incomplete
      bladder emptying and recurrent urinary tract infections in an 87-year-old man,
      was successfully excised endoscopically. The technique and possible future
      indications are described.

PMID- 1387423
TI  - [Complication and prognosis in essential hypertension].

PMID- 1387422
TI  - The problem of discrimination in health care priority setting.
AB  - Increasingly stringent fiscal restrictions on the scope of medical services
      available to patients have resulted in calls for explicit health care priority
      setting. Several commentators have called for the application of decision
      analytic principles to such efforts, which would assign services priority based
      on the extent to which they produce preferred health outcomes. The Oregon
      Medicaid exercise is an example of such a process. An important challenge to
      these utilitarian efforts is the need to avoid discrimination against people with
      medical disabilities. Both of the key elements entailed by decision-analytic
      approaches to priority setting--estimation of outcomes and assignment of values
      to those outcomes--are vulnerable to charges of discrimination, primarily because
      both the medical outcomes expected in disabled individuals and the values they
      place on those outcomes may differ from the general public. Priority-setting
      efforts must proceed carefully to avoid the appearance (and reality) of
      discrimination.

PMID- 1387424
TI  - [Progression of the left ventricular hypertrophy].

PMID- 1387426
TI  - [Low renin hypertension].

PMID- 1387425
TI  - [Cardiac hypertrophy in hypertension].

PMID- 1387427
TI  - [Diurnal variation of blood pressure in salt-responder].

PMID- 1387428
TI  - [Reconstructive surgery of renovascular hypertension].

PMID- 1387429
TI  - [Hypertension in thyroid disease].

PMID- 1387430
TI  - [Clinical problems associated with long-term antihypertensive treatment].

PMID- 1387431
TI  - [Study of yearly changes in intractable disease patients receiving financial aid
      for treatment].
AB  - Yearly changes of intractable disease patients receiving financial aid for
      treatment were observed for 24 intractable disease patients from 1983 to 1987.
      The results obtained were as follows. 1. The number of intractable disease
      patients receiving financial aid for treatment increased from 1983 to 1987 for 23
      of the diseases. Only the number of SMON patients did not increase. 2. Medical
      care expenditures for these patients also increased since 1983. Greater increases
      for in-patients than for out-patients were seen for Huntington's chorea and
      Behcet's disease, while larger increases were seen for out-patients with
      Parkinson's disease, Scleroderma.dermatomyositis.primary multiple myositis,
      Buerger's disease, and others. 3. The proportion of national health insurance
      holders among intractable disease patients was 42.1% as compared with 34.7% among
      total national patients. The proportion was especially higher for Huntington's
      chorea (64.6%), Parkinson's disease (64.1%) and SMON (59.4%) patients.

PMID- 1387433
TI  - Nifedipine versus fosinopril in uninephrectomized diabetic rats.
AB  - Antihypertensive agents have been shown to exert inequivalent effects on
      glomerular injury in experimental renal disease models. To compare the
      consequences of dissimilar antihypertensive regimens on the development of
      diabetic glomerulopathy, studies were performed in three groups of
      uninephrectomized moderately hyperglycemic diabetic rats. One group (DM) received
      no therapy except insulin. The remaining groups received insulin and either the
      angiotensin I converting enzyme inhibitor, fosinopril (FOS), or the calcium
      channel blocker, nifedipine (NIF). Both drugs lowered blood pressure comparably.
      At four to eight weeks, DM rats exhibited elevation of the single nephron
      glomerular filtration rate (SNGFR), due to elevations of the glomerular capillary
      plasma flow rate (QA) and the glomerular capillary hydraulic pressure (PGC).
      Neither NIF nor FOS affected values for SNGFR or QA. However, while FOS lowered
      PGC and increased Kf, NIF did not affect these parameters. In longer term (8
      month) studies, DM rats exhibited progressive albuminuria and glomerular
      sclerosis. FOS markedly limited development of albuminuria and glomerular injury,
      but NIF was ineffective in limiting either parameter of glomerular injury. Thus,
      in contrast to the beneficial effects of converting enzyme inhibitors, chronic
      calcium channel blockade with nifedipine fails to limit PGC or glomerular injury
      in diabetic rats. These findings lend further support to the concept that
      different classes of antihypertensive agents are not equally effective in
      protecting against diabetic glomerulopathy.

PMID- 1387432
TI  - Relationships among natriuresis, atrial natriuretic peptide and insulin in
      insulin-dependent diabetes.
AB  - Insulin-dependent diabetic patients have a large exchangeable body sodium pool,
      secondary to sodium retention. The pathogenesis of impaired natriuresis in
      insulin dependent diabetes remains to be elucidated. The present study examines
      the role of hyperinsulinemia, impaired atrial natriuretic release, and resistance
      to atrial natriuretic peptide action in determining sodium retention in
      normotensive and hypertensive insulin-dependent diabetic patients. Eight insulin
      dependent diabetic patients had significantly higher daily sodium excretion rate
      (147 +/- 16 mmol/day; mean +/- SE) during conventional insulin treatment (daily
      plasma glucose: 11.6 +/- 1.2 mmol/liter; daily plasma insulin: 27 +/- 3
      microU/ml) than during intensified insulin treatment (daily sodium excretion
      rate: 91 +/- 12, P less than 0.01; daily plasma glucose: 6.8 +/- 0.7, P less than
      0.01; daily plasma insulin: 44 +/- 4, P less than 0.01). Daily sodium excretion
      rate was also significantly lower (107 +/- 13, P less than 0.01) in the same
      diabetic patients during intensified insulin treatment along with hyperglycemic
      clamp (daily plasma glucose: 12.8 +/- 0.3, NS; plasma insulin 48 +/- 4, P less
      than 0.01). Seven control subjects had lower extracellular liquid volume than
      eight insulin-dependent diabetic patients (11.0 +/- 0.8 l/1.73 m2 vs. 14.8 +/-
      0.9, P less than 0.05) and also had baseline plasma atrial natriuretic peptide
      concentrations (18 +/- 5 pg/ml vs. 37 +/- 4, P less than 0.05). Atrial
      natriuretic peptide response to saline challenge was blunted in insulin-dependent
      diabetic patients when saline was administered on the basis of body surface area
      (90 mmol/1.73 m2.90 min) but not when administered on the basis of extracellular
      liquid volume (ECV) (8.2 mmol/liter ECV.90 min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387434
TI  - Urinary C3dg and C5b-9 indicate active immune disease in human membranous
      nephropathy.
AB  - We have measured complement activation markers, C3dg and C5b-9 in plasma and
      urine from patients with idiopathic membranous nephropathy and IgA nephropathy.
      There was no significant difference in levels of plasma C5b-9 between the patient
      groups. However, high plasma concentrations of C3dg were associated significantly
      with IgA nephropathy with 45% of patients having levels over 25 U/ml (P less than
      0.001). High concentrations of urinary C3dg and C5b-9 were associated
      significantly with membranous nephropathy (43% and 43% of the patient group,
      respectively) compared to patients with IgA nephropathy (10% and 0%,
      respectively, P less than 0.001). In a retrospective analysis of 31 patients with
      membranous nephropathy, 66% of patients with high initial urinary C5b-9 showed an
      unstable clinical course compared to 18% of patients with initially absent or low
      C5b-9 (P less than 0.001). We suggest that high urinary C5b-9 identifies those
      patients with a membranous lesion which retains an active immunological component
      contributing to the pathology of progressive glomerular damage.

PMID- 1387436
TI  - Reduced glomerular thromboxane receptor sites and vasoconstrictor responses in
      diabetic rats.
AB  - Glomerular thromboxane production and urinary thromboxane excretion are increased
      in early diabetes, but in spite of this renal blood flow and glomerular
      filtration rate are significantly higher than in control animals. To study the
      possibility of a defect in thromboxane actions in the kidney, we have measured
      glomerular thromboxane receptors and the renal hemodynamic response to the
      administration of a stable thromboxane analog in diabetic rats. Glomerular
      thromboxane receptors were studied in hyperglycemic diabetic rats 7 to 10 days
      after injection of streptozotocin (65 mg/kg, i.v.) and in normal controls.
      Scatchard analysis of equilibrium binding using the thromboxane antagonist, [3H]
      SQ29548, demonstrated one class of high affinity thromboxane receptor sites in
      control (Kd = 19.9 +/- 2.6 nM, N = 16) and diabetic rats (Kd = 19.8 +/- 2.1 nM, N
      = 8, P = NS). The number of thromboxane receptors was reduced by 44% in diabetic
      rats (control, 374 +/- 20 vs. diabetic, 210 +/- 21 fmol/mg, P less than 0.01).
      Thromboxane binding in diabetic rats was not restored to normal levels by
      thromboxane synthetase inhibition with OKY046. Diabetic rats had higher renal
      blood flow (diabetic, 7.03 +/- 0.18 vs. control, 6.33 +/- 0.13 ml/min, P less
      than 0.05) and glomerular filtration rate (2.42 +/- 0.10 vs. 1.96 +/- 0.07
      ml/min, P less than 0.05). Infusion of the stable thromboxane agonist, U46619
      (0.1 micrograms/kg/min), reduced renal blood flow and glomerular filtration rate
      in all animals, but the constrictor responses were blunted by 50% in
      hyperglycemic diabetic rats compared with normal controls or euglycemic diabetic
      rats (P less than 0.05). Control of blood glucose with insulin normalized the
      number of glomerular thromboxane receptor sites, reversed hyperfiltration and
      restored glomerular responses to thromboxane agonist. The abnormalities of
      glomerular thromboxane receptors are similar to changes in angiotensin II
      receptors, and suggest a generalized defect in vasoconstrictor receptors in the
      diabetic kidney.

PMID- 1387435
TI  - Thromboxane receptor blockade reduces renal injury in murine lupus nephritis.
AB  - To investigate the role of thromboxane A2 (TxA2) in murine lupus, we assessed the
      effects of the specific thromboxane receptor antagonist GR32191 on immune complex
      glomerulonephritis in MRL-lpr/lpr mice. Forty mg/kg/day GR32191 was given by
      twice daily subcutaneous injection for eight weeks beginning at 12 weeks of age.
      This dose completely blocked the renal vasoconstriction produced by the
      thromboxane agonist U46619. After eight weeks of treatment, both glomerular
      filtration rate (GFR) (8.9 +/- 0.6 vs. 6.8 +/- 1.1 ml/min/kg; P less than 0.05)
      and PAH clearance (CPAH) (37.4 +/- 2.5 vs. 29.9 +/- 3.3 ml/min/kg; P less than
      0.05) were significantly higher in mice given GR32191 compared to vehicle treated
      animals. Administration of GR32191 also reduced proteinuria from 18.1 +/- 11.6 to
      3.7 +/- 1.3 mg/24 hours (P less than 0.05). In GR32191 treated MRL-lpr/lpr mice,
      renal hemodynamic function and proteinuria were not significantly different from
      congenic MRL-+/+ controls. Thromboxane receptor blockade had striking affects on
      renal histomorphology reducing both hyaline thrombi in glomeruli (P = 0.022) and
      interstitial inflammation (P = 0.006). Glomerular crescents and severity of
      vasculitis also tended to be reduced in mice receiving the thromboxane receptor
      antagonist. The overall histopathologic score in mice given GR32191 was
      significantly lower than vehicle treated animals (4.7 +/- 0.5 vs. 8.4 +/- 1.5; P
      = 0.016). These effects of GR32191 were associated with decreased excretion of
      thromboxane B2 (TxB2) in urine (292 +/- 37 vs. 747 +/- 155 pg/24 hr; P less than
      0.005) as well as a modest reduction in glomerular deposits of IgG
      (semiquantitative score 2.6 +/- 0.2 vs. 3.5 +/- 0.2; P less than 0.02). Thus,
      chronic thromboxane receptor blockade markedly altered the course of renal
      disease in MRL-lpr/lpr mice, suggesting that TxA2 is an important mediator of
      renal dysfunction and injury in this murine model of lupus nephritis.

PMID- 1387437
TI  - Antibiotic prophylaxis for cardiothoracic operations. Meta-analysis of thirty
      years of clinical trials.
AB  - Antistaphylococcal penicillins and first-generation cephalosporins have
      traditionally been the prophylactic antibiotics of choice for patients undergoing
      cardiothoracic operations. Recently published studies have claimed improved
      outcomes with respect to postoperative wound infection when second-generation
      cephalosporins were used for prophylaxis. The purpose of this study was to
      critically review the infectious outcomes of prospective, randomized, and
      controlled studies of cardiothoracic surgery prophylaxis by means of meta
      analytic techniques. For each of 28 studies meeting the meta-analysis entry
      criteria, odds ratios with 95% confidence intervals were calculated to compare
      the prophylactic efficacy of the antibiotic regimens. Odds ratios were then
      pooled, and a summary odds ratio was calculated for each pairing of antibiotic
      treatments. Placebo-controlled trials of cardiothoracic prophylaxis demonstrated
      a consistent benefit to the administration of antibiotic prophylaxis, with an
      approximate fivefold reduction in wound infection rate. The second-generation
      cephalosporins, cefamandole and cefuroxime, performed better than cefazolin, with
      an approximate one and one-half-fold reduction in wound infection rate.
      Administration of prophylaxis beyond 48 hours was not associated with improved
      infectious outcomes.

PMID- 1387438
TI  - Postoperative erythroderma after cardiac operations. The possible role of
      depressed cell-mediated immunity.
AB  - Erythroderma as a manifestation of graft-versus-host disease after cardiac
      operations with blood transfusion may occur more frequently in Japan than in
      other countries. We have seen this problem in five patients who, after heart
      operations, died with symptoms and signs characteristic of graft-versus-host
      disease: cutaneous eruption, fever, diarrhea, leukopenia associated with
      agranulocytosis, and liver dysfunction. In the three patients seen most recently,
      skin biopsy showed findings similar to those of graft-versus-host disease after
      bone marrow transplantation. In addition, immunologic investigation showed
      remarkable differences in the findings in these patients and in those who did not
      have a graft-versus-host disease-like syndrome after cardiac operations. In
      particular, interleukin-2 production in response to mitogen stimulation was
      markedly diminished after operation in our patients, and the ratio of OKT4+ cells
      to OKT8+ cells in peripheral blood was low, reflecting increased numbers of OKT8+
      cells after the occurrence of symptoms. The results raise the possibility that
      transient depression of cellular immunity after cardiac operations with blood
      transfusion may contribute to the occurrence of postoperative acute graft-versus
      host disease.

PMID- 1387439
TI  - Fibrin sealant for early repair of acquired ventricular septal defect.
AB  - The trend toward early operation for acquired ventricular septal defects exposes
      the patient to major perioperative bleeding and residual shunt because of the
      fragility of the recently necrosed myocardium. To reduce these complications we
      have used a fibrin sealant to reinforce the cardiac tissues in addition to the
      usual closure of the defect with a Dacron patch through a left ventricular septum
      around the defect, area. During cardiac arrest fibrin sealant is applied on the
      ventricular septum around the defect, between the septum and the patch, and on
      the edges of the ventriculotomy. This technique was used in three patients (mean
      age 68.2 years) operated on for an acquired ventricular septal defect within 4
      days of the infarction and within 24 hours of the occurrence of the defect. Low
      postoperative bleeding, absence of recurrent shunt, and good ventricular function
      indicated satisfactory surgical result in all three patients. We suggest that the
      use of fibrin sealant during operations for acquired ventricular septal defects,
      by reinforcing the necrotic and fragile tissues, may reduce perioperative
      bleeding and assure a more solid implantation of the patch.

PMID- 1387441
TI  - Cytokines--an overview.

PMID- 1387440
TI  - Single lung transplantation in rats with fatal pulmonary hypertension.
AB  - Effects of single lung transplantation on fatal pulmonary hypertension were
      evaluated in rats receiving a lethal dose of monocrotaline. Inbred rats treated
      with monocrotaline (80 mg/kg) received a left lung isograft at 4 weeks (n = 9)
      and at 6 weeks (n = 6), when moderate and severe pulmonary hypertension,
      respectively, had developed. Medicated (n = 12) and nonmedicated rats (n = 12)
      served as control animals. Each rat was tested weekly with treadmill for exercise
      tolerance and oxygen consumption during a 10-week period after medication and
      after they were killed. Medicated control rats lost exercise tolerance and
      highest oxygen consumption per unit time consistently to the range of resting
      value (or 45% of nonmedicated control rats), and all died from severe pulmonary
      vascular occlusive disease with right ventricular hypertrophy before 10 weeks
      (right ventricular/left ventricular weight ratio of 1.16). All rats receiving a
      left lung isograft at 4 weeks survived and regained highest oxygen consumption
      per unit time (87% of nonmedicated control rats), with the lung transplant
      receiving 65% (nonmedicated control rats, 39%) of cardiac output and milder right
      ventricular hypertrophy (right ventricular/left ventricular weight ratio of
      0.46). Except for one, all rats that received a left lung isograft at 6 weeks
      tolerated single lung transplantation, but they died soon after reperfusion
      because of pulmonary edema in the graft that received 58% of cardiac output with
      right ventricular/left ventricular weight ratio of 0.79. Results of single lung
      transplantation in rats were dependent on severity of pulmonary hypertension. In
      rats with moderate pulmonary hypertension, single lung transplantation was
      successful in reversing exercise intolerance and right ventricular hypertrophy.
      Single lung transplantation was unsuccessful when pulmonary hypertension was
      severe in the rat model because increased flow toward the lung transplant
      resulted in graft pulmonary edema.

PMID- 1387442
TI  - Efficacy of danazol treatment in infertile patients with endometriosis.
AB  - The study was done to assess the efficacy of danazol in the treatment of
      infertile patients with all stages of endometriosis. The cumulative pregnancy
      rates in 21 patients with Stage I and II endometriosis were compared to 21
      patients with Stage III and IV endometriosis. Both groups had danazol treatment
      for six months. All other fertility related factors were controlled for in both
      groups. There was a cumulative pregnancy rate of 11% (standard error 7%) at 12
      months of follow-up in the group with Stage I and II disease whilst it was 26%
      (standard error 10%) in the group with moderate or severe disease. These results
      question the validity of any classification system in prognosticating for
      fertility in patients with endometriosis.

PMID- 1387443
TI  - Legionella species isolated from cooling towers in Kuala Lumpur.
AB  - Three building complexes in Kuala Lumpur were surveyed for the presence of
      legionellae in cooling towers. The organisms were grown from 12 out of 46 samples
      of water collected from 30 towers. L. pneumophila serogroups 1 and 7 were the
      commonest serogroups isolated. None belonged to the Pontiac subgroup of L.
      pneumophila serogroup 1.

PMID- 1387444
TI  - Incidence of postdural puncture headache. A prospective study of 101 spinal
      anaesthetics in orthopaedic patients.
AB  - Spinal anaesthesia was performed on 101 patients with a 25-Gauge (0.52 mm)
      needle. We found a 13.9% overall incidence of postdural puncture headache (PDPH)
      in an orthopaedic population whose mean age was 33.6 years. This incidence is too
      high and an alternative technique may be needed.

PMID- 1387445
TI  - A comparison of sodium citrate and sodium citrate/ranitidine combination for acid
      aspiration prophylaxis.
AB  - The effectiveness of sodium citrate and sodium citrate/ranitidine were compared
      in two randomised groups of elective caesarean patients during the various phases
      of anaesthesia. The mean pH values (3.5, 3.3, 3.6) were lower in the citrate
      group compared to the citrate/ranitidine group (6.1, 6.3, 5.9). The percentage of
      patients with pH values less than 2.5 was 40% in the citrate group compared to 7%
      in the citrate/ranitidine group. Sodium citrate alone is less effective than
      sodium citrate/ranitidine for acid aspiration prophylaxis.

PMID- 1387446
TI  - Peptide regulatory factors. Intercellular signalling molecules regulating tissue
      (re) modelling.

PMID- 1387447
TI  - Anaesthesia for closed embolisation of cerebral arteriovenous malformations.
AB  - Anaesthetic experience of the first nine patients in Singapore who underwent
      closed embolisation of cerebral arteriovenous malformations is reported. Six
      patients had neurolept analgesia and three had general anaesthesia.

PMID- 1387448
TI  - Post-menopausal smear patterns--a review of vaginal smears in 480 women.
AB  - Cytohormonal evaluation was done on the vaginal smears of 480 normal,
      asymptomatic, post-menopausal women whose ages ranged from 36 to 74 years. About
      50% showed atrophic smears consistent with total oestrogen lack. 41% had mild to
      moderately proliferative smears compatible with sub-optimal oestrogen stimulus.
      9% showed a highly proliferative pattern typical of unopposed oestrogen effect
      and in this group two women had atypical endometrial cells in their smears, which
      subsequently were found to come from an atypical endometrial hyperplasia and an
      endometrial adenocarcinoma-in-situ. The clinical relevance of cytohormonal
      studies in post-menopausal women is briefly discussed.

PMID- 1387449
TI  - A microbiological study of vaginal discharge in women attending a Malaysian
      gynaecological clinic.
AB  - Vaginal discharge is a common complaint of women attending gynaecological
      clinics. The purpose of this study was to compare the occurrence of commonly
      implicated microorganisms in vaginal discharge amongst women with or without the
      complaint, attending a gynaecological and family planning clinic. The association
      of Gardnerella vaginalis with bacterial vaginosis was also studied. It was found
      that there were no significant differences between the cases and controls in the
      isolation rate of Gardnerella vaginalis, Torulopsis glabrata, Ureaplasma
      urealyticum, Mycoplasma ssp and Group B streptococcus (p greater than 0.05). Only
      the isolation rate of Candida albicans was significantly higher in the cases than
      controls (p less than 0.01). However, there was a significant association of G.
      vaginalis with bacterial vaginosis.

PMID- 1387450
TI  - Incidence and management of middle ear effusion in cleft palate patients.
AB  - For a complete overall rehabilitation of cleft palate patients a multi
      disciplinary approach should be adopted. Plastic and Head and Neck Surgeons in
      whom most of the treatment are entrusted should be concerned not only at
      achieving palatal function and cosmetic acceptability but also the various other
      problems associated with cleft palate especially hearing loss. In this study, 66
      patients with repaired and unrepaired cleft palates were examined for the
      presence of hearing loss due to middle ear effusion. The incidence of middle ear
      effusion was high (57.6%). It was also found that only eight of these patients
      (12.1%) ever complained of hearing loss or any associated symptoms and repair of
      the cleft palate did not influence the incidence of middle ear effusion. As such,
      screening should be done in all cleft palates and otolaryngologists should
      therefore play an important role in the multi-disciplinary team which should
      comprise the paediatrician, plastic surgeon, speech therapist, orthodontist and
      dental specialist.

PMID- 1387451
TI  - Morbidity and mortality of infants of diabetic mothers born at the Maternity
      Hospital, Kuala Lumpur.
AB  - A prospective study was carried out in the Maternity Hospital, Kuala Lumpur in
      1989 to determine the morbidity and mortality of infants of diabetic mothers. Out
      of 24,856 neonates born during the study period, 54 neonates (2.2 per 1000
      livebirths) were born to mothers who were diagnosed to have diabetes mellitus
      before the current pregnancy or who had impaired glucose tolerance test during
      the current pregnancy. Almost a third (29.6 percent) of these infants of diabetic
      mothers had birthweight of 4000 grams and above, and 37.0 percent of the 54
      babies were large-for-gestational age. Hypoglycemia occurred in 9/54 (16.7
      percent) of the neonates, respiratory distress syndrome in 5/54 (9.3 percent),
      shoulder dystocia in 7/54 (13.0 percent), and congenital abnormalities in 4/54
      (7.4 percent). Three (5.6 percent) neonates died during the neonatal period. The
      results of this study suggest a need to intensify control of maternal diabetes
      mellitus during pregnancy in order to reduce the rates of morbidity and mortality
      of their infants.

PMID- 1387452
TI  - A retrospective review of tracheal suction at birth in neonates with meconium
      aspiration syndrome.
AB  - A retrospective study of 54 neonates with Meconium Aspiration Syndrome (MAS)
      admitted to the Paediatric ICU Penang General Hospital from January 1989-December
      1990 was carried out to determine if suction of the trachea at birth was
      performed in this group of patients. 63% were inborn and 27% outborn. The mean
      birth weight was 3.2 kg, 83% were ventilated, mean duration of ventilation was
      five days and the mortality was 24%. 63% had an Apgar Score of less than 5 at 1
      min and 65% had thick meconium-stained liquor. Only 48% were intubated and
      suctioned at birth. Overall tracheal suction rate was low.

PMID- 1387453
TI  - Modified subtotal cholecystectomy: a procedure for the difficult gall bladder.
AB  - Modified subtotal cholecystectomy involves removal of the gall bladder after
      circumferential division of the neck. Either the impacted stone or the surgeons
      finger was used as a guide to identify the neck. The stump cavity in the neck is
      obliterated with interrupted sutures to prevent recurrent stone formation.
      Indications for this procedure are obscure anatomy, due either to the severe
      inflammation in acute cholecystitis or dense adhesions in the small fibrosed gall
      bladder. The decision to perform modified subtotal cholecystectomy is taken
      during the operation. Forty three patients (14%) underwent this procedure during
      the period between August 85 and April 90. Out of 289 cholecystectomies performed
      seven were emergency and thirty-six were early cholecystectomies. With the
      increasing trend towards urgent and early cholecystectomy in acute cholecystitis
      the author has found this to be a safe and definitive procedure.

PMID- 1387454
TI  - Allergic skin tests in Malaysian asthmatics.
AB  - To assess the prevalence of skin test sensitivity among asthmatic patients in
      Malaysia, skin prick tests for allergy in 134 adult asthmatic patients and 120
      control subjects were done. 90% of asthmatic patients had positive skin test to
      at least one allergens as compared to 78% of the controls. House dust mite was
      the most frequent allergen to which the subjects had positive reactions. Sixty
      four percent of the asthmatic patients had associated rhinitis. There was no
      significant difference in the skin test sensitivity between asthmatic patients
      with associated rhinitis and those without.

PMID- 1387455
TI  - Total occlusion of left main coronary artery in a patient with chronic, stable
      angina.
AB  - We report a case of total occlusion of the left main coronary artery (LMCA) in a
      patient with chronic, stable angina. Total occlusion of the LMCA is rare and
      survival depends on the existence of collateral circulation. In LMCA disease,
      there is usually also disease in other parts of the coronary arterial tree.

PMID- 1387456
TI  - Early experiences of intra-operative trans-oesophageal echocardiography (TEE) in
      mitral valve repair.
AB  - Whenever possible Mitral valve repair should be performed instead of Mitral valve
      replacement. It is important to assess the adequacy of the repair during the
      operation so that any corrective steps may be taken immediately. We present three
      cases of Mitral valve repair in which the intraoperative TEE was used to assess
      the adequacy of the repair. There was good correlation of the immediate post
      bypass TEE findings and early post operative transthoracic echocardiographic
      findings. Intraoperative TEE is a useful tool in the early assessment of Mitral
      Valve Repair.

PMID- 1387457
TI  - Phaeochromocytoma during pregnancy: ultrasound and MRI appearances.

PMID- 1387458
TI  - Typhonium divaricatum (rodent tuber): a promising local plant in the fight
      against cancer.

PMID- 1387459
TI  - [Evaluation of nutritional status in patients with esophageal cancer by
      measurement of sternocleidomastoid, rectus abdominis and quadriceps muscles on
      ultrasound imaging].
AB  - To assess the nutritional status of the patients with esophageal cancer, we
      measured the areas of sternocleidomastoid and rectus abdominis muscles (SMA,
      RAMA) on real time ultrasound imaging and calculated muscle index (MI =
      (SMA+RAMA/Height)). Eighty-three patients with esophageal cancer were included in
      the present study. Preoperatively, significant Spearman's coefficients were found
      between MI and the percentage of standard arm circumference (R = 0.52) and
      between MI and the percentage of standard arm muscle circumference (R = 0.51).
      Postoperatively, patients with wide muscle area showed high values of prealbumin,
      transferrin and fibronectin. To study the changes after surgery, we also measured
      the area of quadriceps muscle in patients with esophageal cancer. The areas of
      quadriceps muscle in patients with dysphagia were much diminished than in those
      without dysphagia. Measurement of areas of muscles such as SMA, RAMA and
      quadriceps muscle was proved to be a useful procedure in evaluating the
      nutritional status of patients with esophageal cancer.

PMID- 1387460
TI  - [Assessment for protective effects of CoQ10, PGE1 and TXA2 receptor antagonist
      (ONO-3708) on warm ischemic liver].
AB  - Metabolic disturbances in the canine liver during warm ischemia by Pringle's
      method for 60 minutes and the role of Coenzyme Q10 (CoQ10), Prostaglandin E1
      (PGE1) and ONO-3708, TXA2 receptor antagonist, were studied. Mongrel dogs were
      divided into five groups; control group, group of liver ischemia without drugs,
      groups of liver ischemia with CoQ10, PGE1 and ONO-3708 pretreatment. Metabolic
      rates of PGI2, TXA2, insulin, glucagon and glucose and production of lipid
      peroxides in the five groups were measured at the points before Pringle's
      procedure, 5 minutes, 60 minutes and 120 minutes after declamping. In the group
      of ischemia without drug administration, the hepatic metabolism of PGI2, TXA2,
      insulin and glucose were decreased after declamping. The metabolism of glucagon,
      however, was not disturbed by warm ischemia. The production of lipid peroxides
      increased at 5 minutes after declamping. In the groups of CoQ10, PGE1 and ONO
      3708 pretreatment, changes of PGI2, TXA2 and insulin metabolism in the liver were
      improved, and an increased production of lipid peroxides by warm ischemia was
      normalized. This study suggests that CoQ10, PGE1 and ONO-3708 protect liver
      damage by warm ischemia as results of improvement of metabolic disturbances of
      PGI2, TXA2, insulin and suppression of lipid peroxides production.

PMID- 1387461
TI  - Characterization of fumonisin toxicity in orally and intravenously dosed swine.
AB  - Fumonisin B1 (FB1), a recently identified mycotoxin produced by Fusarium
      moniliforme in corn, has been shown to cause death in swine due to pulmonary
      edema, an apparently species specific effect, and to interfere with sphingolipid
      metabolism in vitro. Here we characterize the toxicity of fumonisins, using
      female cross-bred swine weighing 6 to 13 kg, and present a hypothesis regarding
      the mechanism of fumonisin-induced pulmonary edema in swine. FB1 was given daily
      intravenously (IV) to pig 1 for 9 days for a total of 72 mg (7.9 mg/kg) and to
      pig 2 for 4 days for a total of 67 mg (4.6 mg/kg). Pig 3 (control) was given
      saline IV for 9 days. Corn screenings naturally contaminated with FB1 (166 ppm)
      and FB2 (48 ppm) were fed to pigs 4, 5, and 6, and ground corn was fed to pigs 7
      and 8 (controls). Pigs 4 and 7 were killed on day 5; pig 5 was found dead on day
      6; and pigs 6 and 8 were killed on day 15. Pigs 4 and 5 had ingested 187 and 176
      mg total fumonisins, respectively, while pig 6 had ingested 645 mg. Feed
      consumption had decreased in pigs fed corn screenings, with an additional sharp
      decrease prior to onset of clinical signs. Increases in serum liver enzymes,
      total bilirubin, and cholesterol were present, but electrocardiograms, heart
      rate, and body temperature were unaffected. Pigs dosed IV with FB1, developed
      mild intermittent respiratory abnormalities, while those fed screenings developed
      respiratory distress within 5 days. Mild interstitial pulmonary edema was
      observed in pig 1. Severe interstitial pulmonary edema, pleural effusion, and
      increased lung wet/dry weight ratio were observed in pigs 4 and 5. All pigs given
      fumonisin (either IV or orally) had hepatic changes characterized by hepatocyte
      disorganization and necrosis; pancreatic acinar cell degeneration was also
      observed. Ultrastructural changes in orally dosed swine included loss of
      sinusoidal hepatocyte microvilli; membranous material in hepatic sinusoids; and
      multilamellar bodies in hepatocytes, Kupffer cells, pancreatic acinar cells and
      pulmonary macrophages. Pulmonary intravascular macrophages (PIMs) contained large
      amounts of membranous material. Thus, the target organs of fumonisin in the pig
      are the lung, liver, and pancreas. At lower doses, slowly progressive hepatic
      disease is the most prominent feature, while at higher doses, acute pulmonary
      edema is superimposed on hepatic injury and may cause death. We hypothesize that
      altered sphingolipid metabolism causes hepatocellular damage resulting in release
      of membranous material into the circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1387463
TI  - Paralimbic frontal lobe hypometabolism in depression associated with Huntington's
      disease.
AB  - We measured regional cerebral glucose metabolism using 2-[18F]-fluoro-2-deoxy-D
      glucose and positron emission tomography in depressed and nondepressed patients
      with early Huntington's disease (HD), compared with appropriately matched
      controls. Caudate, putamen, and cingulate metabolism was significantly lower in
      patients with HD than in control subjects, independent of mood state. Orbital
      frontal-inferior prefrontal cortex hypometabolism, however, differentiated
      depressed patients from both nondepressed patients and normal controls. These
      findings implicate selective dysfunction of the paralimbic regions of the frontal
      lobes in the mood disorder of HD. The metabolic pattern is similar to that in
      depression associated with Parkinson's disease, suggesting that the integrity of
      pathways linking paralimbic frontal cortex and the basal ganglia may be integral
      to the normal regulation of mood.

PMID- 1387462
TI  - Regional distribution of monoamines and dopamine D1- and D2-receptors in the
      striatum of the rat.
AB  - Dopamine (DA) D1- and D2-receptor densities were determined in 18 discrete areas
      of the caudate-putamen-globus pallidus of male Wistar rats and compared to local
      DA concentrations. All three parameters were found to decrease caudally. The
      globus pallidus was distinguished by the low concentration of DA and its
      receptors and high noradrenaline (NA) content. While there were no mediolateral
      differences in DA or DA D1-receptors, a clear mediolateral gradient was observed
      for DA D2-receptors which extended over several sections of the brain. The ratio
      of DA D1- to D2-receptors was significantly higher in the dorsal than in the
      ventral areas of the mediolateral and caudal striatum. This is the first report
      of clear dorsoventral differences in parameters relating to DA activity in the
      striatum. These findings may be of particular significance in understanding the
      functional dichotomy between the dorsal and ventral striatum.

PMID- 1387464
TI  - Serotonergic dysfunction in depression associated with Parkinson's disease.
AB  - A 55-year-old man presented with a 5-year history of Parkinson's disease and a 6
      month history of major depression. The patient's depressive symptoms responded to
      treatment with fluvoxamine, a selective and potent serotonin reuptake inhibitor.
      Tryptophan depletion testing, which acutely lowers central serotonin levels,
      caused a brief exacerbation of the depressive illness, which resolved upon
      tryptophan repletion. Serotonergic dysfunction may be an etiologic factor in
      depression that occurs in Parkinson's disease.

PMID- 1387466
TI  - Task-specific rehab program reduces claims.

PMID- 1387467
TI  - Outcome of preoperative against-the-rule astigmatism after phacoemulsification:
      characteristic changes over time. Part II.
AB  - To determine the outcome of preoperative against-the rule (AR) astigmatism among
      1,648 phacoemulsification and aspiration (PEA) procedures, we analyzed the post
      cataract time course of astigmatism over 6 months in 618 eyes divided into three
      groups. In preoperative AR astigmatism less than 0.75 dptr (n = 208), the
      astigmatism increase 1 week postoperatively was rapid. In preoperative AR
      astigmatism greater than or equal to 1.5 dptr (n = 185), no difference in the
      power of astigmatism was apparent between 1 and 3 months postoperatively. The
      third group (0.75 less than or equal to preoperative AR astigmatism less than 1.5
      dptr, n = 143) showed intermediate characteristics. The eyes with preoperative
      low AR astigmatism showed exacerbation of astigmatism after the PEA procedure,
      whereas the degree of astigmatism, corneal curvatures and the rate of AR
      astigmatism became lower in the eyes with higher preoperative AR astigmatism.

PMID- 1387465
TI  - Towards standardization in gamma camera renography.

PMID- 1387468
TI  - NMDA receptor antagonist MK-801 blocks non-opioid stress-induced analgesia in the
      formalin test.
AB  - The analgesic effect of a 3-min swim stress was assessed using the formalin test.
      Male Swiss mice were injected i.p. with naloxone (0.1 or 1.0 mg/kg), MK-801
      (0.075 mg/kg) or saline 15 min prior to swimming in water maintained at 20
      degrees C or 32 degrees C. The mice were then injected with 20 microliters of 5%
      formalin into the plantar surface of 1 hind paw and pain behaviour (time spent
      licking the injected paw) was continuously monitored during the subsequent 10
      min. Swim stress produced a significant reduction in pain behaviour at both 20
      degrees C and 32 degrees C. MK-801 completely blocked the analgesia produced by
      both the 20 degrees C and 32 degrees C swim. At a dose of 0.1 mg/kg, naloxone
      partially antagonized the analgesia produced by the 32 degrees C swim but did not
      affect the analgesia produced by the 20 degrees C swim. Naloxone at a dose of 1.0
      mg/kg had no effect on swim stress-induced analgesia. Neither MK-801 nor 0.1
      mg/kg naloxone altered baseline pain behaviour, although 1.0 mg/kg naloxone did
      significantly reduce it. It is unlikely that the effect of MK-801 on swim stress
      induced analgesia is due to an interaction with an opioid mechanism, as MK-801
      had no effect on morphine analgesia. These results suggest that the analgesia
      produced by the 20 degrees C swim stress in the formalin test is non-opioid in
      nature and mediated via the NMDA receptor, whereas the 32 degrees C swim stress
      induced analgesia has both an opioid and non-opioid component.

PMID- 1387469
TI  - The treatment of depression in chronic low back pain: review and recommendations.
AB  - The prevalence of major depression in patients with chronic low back pain (CLBP)
      is approximately three to four times greater than that reported in the general
      population. In spite of these high prevalence rates, there have been few
      systematic attempts to investigate the efficacy of treatment for major depression
      in patients with CLBP. While several studies have examined the efficacy of
      antidepressant medication and psychological treatment in patients with chronic
      pain, most of these studies have focused on treating chronic pain rather than
      depression. The few studies that have specifically addressed the treatment of
      depression in CLBP indicate that tricyclic antidepressants and cognitive
      behavioral approaches may be effective means of treating depressed chronic pain
      patients. Clinical issues related to diagnostic confounds, rehabilitation
      outcome, and conceptualizations of the relation between pain and depression are
      discussed. It is argued that, in patients with clinical levels of depression,
      treatment modalities specifically targeting depressive symptomatology deserve
      serious consideration as an integral component of pain management programs.

PMID- 1387470
TI  - [Hereditary glucose-6-phosphate dehydrogenase deficiency in newborn infants].
AB  - Early diagnosis of the deficiency of glucose 6-phosphate dehydrogenase was made
      in examining 428 samples of funic blood from 230 boys and 198 girls. The normal
      level of the enzyme activity was established in red blood cells of the healthy
      newborn with regard to the national and sexual differences. The hereditary
      character of the deficiency of glucose 6-phosphate dehydrogenase was supported in
      37 neonates by analyzing the pedigrees. The enzyme deficiency was associated with
      different forms of hemoglobinopathies: alpha- and beta-thalassemia, structurally
      abnormal hemoglobin S and methemoglobinemia. The considerable prevalence of the
      deficiency of glucose 6-phosphate dehydrogenase was revealed in Azerbaijan for
      the first time. The phenotypic frequency amounted to 8.64% whereas the gene one
      to 0.0623.

PMID- 1387471
TI  - [Diagnosis and prevention of health status disorders in children returning after
      treatment from contrasting climatic-geographic zones].

PMID- 1387472
TI  - [Experience in the activities of a children's city hospital during
      intensification of the use of bed capacity under the circumstances of economic
      experiments].

PMID- 1387473
TI  - [Experience in the work of home care services].

PMID- 1387474
TI  - [Course of viral hepatitis B during 1st year of life in children with hypotrophy
      depending on the mode of feeding].

PMID- 1387475
TI  - An assessment of the pharmacokinetics and pharmacodynamics of single doses of
      amlodipine in elderly normotensives.
AB  - This study characterizes the single dose pharmacokinetic characteristics of the
      dihydropyridine calcium antagonist drug amlodipine in a group of 16 elderly
      subjects, aged 65 to 86 years (8 M:8 F). The most notable pharmacokinetic
      features were a prolonged terminal elimination half life of 48 +/- 16 hours and a
      delayed tmax of 7.3 +/- 1.3 hours. Consistent with the time to achieve peak
      plasma drug concentrations, there was a modest but significant reduction in blood
      pressure at 6-8 hours after dosing. Comparison of these results with those of
      published data for young subjects indicate not only a greater degree of
      intersubject variability but also a longer half life in the elderly, suggestive
      of reduced drug clearance, which may lead to higher plasma drug concentrations
      particularly at steady state.

PMID- 1387477
TI  - First-trimester maternal serum human chorionic gonadotrophin as a marker for
      fetal chromosomal disorders. The Dutch Working Party on Prenatal Diagnosis.
AB  - The Dutch Working Party on Prenatal Diagnosis has initiated a study on the
      possibilities of first-trimester screening for fetal chromosomal disorders. We
      report on maternal serum human chorionic gonadotrophin (MS-hCG) measurements in
      1348 pregnancies with a chromosomally normal fetus and 53 pregnancies with a
      chromosomally abnormal fetus. The median MS-hCG concentration in 24 pregnancies
      with Down's syndrome was 1.19 multiples of the normal median (MoM). The MS-hCG
      distributions in normal and Down's syndrome pregnancies did not differ
      significantly (t-test: t = 1.945, p greater than 0.05). We also found no
      difference between normal pregnancies and pregnancies with other chromosomal
      disorders (six cases of trisomy 18, MoM = 0.80; four cases of sex chromosome
      abnormality, MoM = 1.01; 17 cases of chromosomal mosaicism in chorionic villi,
      MoM = 1.11). Selecting an upper limit at the 90th centile could detect 25 per
      cent of pregnancies with Down's syndrome. We conclude that, in the first
      trimester, MS-hCG as a screening factor for Down's syndrome is of minor value.
      However, MS-hCG could be a useful factor in a first-trimester screening programme
      based on a combination of markers.

PMID- 1387476
TI  - Comparative study of the EEG profile of neuroleptics selective for D-1 or D-2
      dopamine receptors in the rabbit.
AB  - The neuroleptics SCH 23390 and raclopride, which interact selectively with either
      D-1 or D-2 dopamine receptor, were studied for their effects on
      electroencephalographic (EEG) activity in the rabbit. Haloperidol (0.3 and 1
      mg/kg intravenously, i.v.), which was used for comparison, induced
      synchronization of the cortical EEG activity. Spectral EEG analysis showed
      increase of power in the whole frequency range (0.1-38.5 Hz) and in all frequency
      bands in the cortex, whereas a slight decrease of slow and fast theta activity
      (3.7-7.2 and 7.2-12.2 Hz) was observed in the hippocampus. Animals appeared
      sedated and arousal response to somatosensory stimuli was markedly inhibited. SCH
      23390 (0.03 and 0.3 mg/kg i.v.) induced periods of cortical synchronization and
      changes of spectral power qualitatively similar to those accompanying haloperidol
      administration. The drug slightly reduced the duration of arousal elicited by
      stimuli. Raclopride (1 and 3 mg/kg i.v.) induced weak EEG changes and little
      effect on arousal response to stimulation. There was an increase of slow wave
      activity which was particularly evident in the hippocampus. The data indicate
      that, although to a lesser degree, the D-1 receptor antagonist SCH 23390 induced
      EEG effects similar to those of haloperidol, whereas blockade of D-2 receptors by
      raclopride resulted in different patterns of EEG activity.

PMID- 1387478
TI  - Variation in the levels of pregnancy-specific beta-1-glycoprotein in maternal
      serum from chromosomally abnormal pregnancies.
AB  - Human pregnancy-specific beta-1-glycoprotein (SP1) was assayed retrospectively in
      stored maternal serum (MS) samples from 82 chromosomally abnormal pregnancies and
      377 matched controls. The median MSSP1 concentration in 48 Down's syndrome
      pregnancies was significantly elevated at 1.17 multiples of the control median
      (MOM), and significantly reduced (0.5 MOM) in a group of eight cases of
      unbalanced translocations. There was no significant difference in median SP1
      concentrations in cases of trisomy 18, trisomy 13, balanced translocations, or
      sex chromosome abnormalities. A comparison with human chorionic gonadotrophin
      results in the same series of samples indicates that SP1 is a less sensitive
      predictor of Down's syndrome pregnancies.

PMID- 1387479
TI  - [Atrial natriuretic peptide in diabetes mellitus patients with arterial
      hypertension].
AB  - The basal level of atrial natriuretic peptide (ANP) of the venous blood plasma
      was investigated in 105 diabetic patients with concomitant arterial hypertension
      (AH) as well as in 20 healthy persons of the same age. Analysis of the results of
      investigation was performed with respect to AH type (essential, atherosclerotic,
      nephrogenic) and expression of cardiac changes. An ANP level in diabetic patients
      without AH did not differ from that of the controls. In the presence of AH this
      level was increased 2-10-fold. The highest level of ANP was observed in patients
      with nephrogenic hypertension and marked cardiac disorders. The results obtained
      suggest the role of ANP in AH pathogenesis.

PMID- 1387480
TI  - [Hormonal regulation of sodium excretion by the kidneys during hunger therapy of
      obese patients].
AB  - Sodium excretion and the blood levels of aldosterone, renin, atrial natriuretic
      peptide (ANP), and insulin were investigated in 9 women with obesity of
      alimentary-constitutional type during hunger therapy and resumed nutrition. It
      has been assumed that restricted sodium excretion with the kidneys during fasting
      is mainly caused by activation of the renin-angiotensin-aldosterone system, with
      ANP contributing to it, insulin not playing the major role in this process.

PMID- 1387481
TI  - Inotropic influence of macrocyclic polyethers on tracheal smooth muscle.
AB  - Incubated guinea pig tracheal smooth muscle exhibited both positive and negative
      inotropic responses to a variety of crown ether analogs that ranged in size from
      12-crown-4 to 30-crown-10 and included molecules whose lipophilicity was modified
      by the addition of benzo- and cyclohexo-substituents on the basic molecular
      framework. The inotropic influence of crown ethers may not only be due to their
      ionophoretic capabilities but may result from their ability to affect alterations
      in membrane physiology.

PMID- 1387483
TI  - A comparison of outcomes using three different methods of breast reconstruction.
AB  - In a review of 325 postmastectomy breast reconstructions, the aesthetic quality
      of the result and the risk of unsuccessful outcome were compared for three
      techniques: tissue expansion (105 breasts), latissimus dorsi myocutaneous flap
      (47 breasts), and TRAM flap (173 breasts). The aesthetic successes achievable
      with the three methods were similar, and some excellent results were achieved
      with each of them. The failure rate after tissue expansion (21 percent) was
      significantly higher than those observed with the TRAM (3 percent) and latissimus
      (9 percent) flaps. Tissue expansion also was not as aesthetically successful as
      other techniques in obese patients. For immediate breast reconstruction, the TRAM
      flap was the most aesthetically successful technique. Although tissue expansion
      has advantages and may be the best choice for some patients, methods that used
      autogenous tissue provided more consistent success.

PMID- 1387484
TI  - The effect of paroxetine on anxiety and agitation associated with depression.
AB  - To assess the effects of treatment on symptoms of anxiety and agitation
      associated with depression, a data base of 2963 paroxetine treated patients was
      compared with 554 who received placebo and 1151 on active control. Paroxetine and
      active control both reduced baseline psychic anxiety more effectively than
      placebo. Both pharmacological treatments were effective in treating somatic
      anxiety with active control demonstrating an earlier onset of activity. Neither
      paroxetine nor active control induced new anxiety symptoms. Paroxetine was
      superior to placebo in the treatment of agitation at Weeks 4 and 6 and to active
      control at Week 4 only. Both paroxetine and active control were more protective
      against emergent (new) agitation than placebo. There was no difference between
      the three groups in the incidence of spontaneously reported adverse events
      indicative of anxiety.

PMID- 1387482
TI  - Effects of cocaine alone and in combination with prazosin or ondansetron on
      multiple fixed-interval fixed-ratio performance in pigeons.
AB  - Three pigeons were trained to respond on a two-component multiple schedule in
      which the components alternated regularly. In one component of the schedule, food
      was presented when the pigeon successfully completed a fixed-interval 120-s
      schedule within 150 s. In the other component of the schedule, food presentation
      occurred when the pigeon managed to complete a fixed-ratio 30 schedule within 30
      s. Once responding had stabilized under both components of the schedule, pigeons
      were challenged with different doses of cocaine alone or cocaine in combination
      with 1.0 mg/kg prazosin (a selective alpha 1-adrenergic antagonist) or 0.10 or
      0.50 mg/kg ondansetron (a selective 5-hydroxytryptamine3 antagonist). All drugs
      were injected intramuscularly 5 min before the start of selected experimental
      sessions. For two subjects, low doses of cocaine increased the low response rates
      maintained by the fixed-interval schedule while decreasing the high rates
      maintained by the fixed-ratio schedule. At intermediate doses, both high and low
      rates decreased but higher rates were more susceptible to disruption than low
      rates. The highest doses of cocaine completely eliminated responding in both
      schedule components. The high-rate behavior of the third subject was not affected
      by low or intermediate doses of cocaine, while low rates decreased at doses up to
      5.6 mg/kg. The higher doses of cocaine eliminated responding in this subject as
      well. Prazosin and both doses of ondansetron antagonized the behavioral effects
      of cocaine at doses that ranged from 1.0-3.0 mg/kg. Redetermination of the dose
      effect curve for cocaine at the conclusion of the experiment revealed that the
      curve had significantly shifted to the right.

PMID- 1387485
TI  - [Biatheletes at the Olympic Games].

PMID- 1387486
TI  - [Sports and handicap].

PMID- 1387487
TI  - [Pelvic pain without evident cause].

PMID- 1387488
TI  - Estimates from the National Health Interview Survey on occupational injury among
      older workers in the United States.

PMID- 1387490
TI  - [Vitamin status of workers in steel-smelting departments of the Karaganda
      Metallurgy Plant].
AB  - The author investigated the vitamin status of workers engaged in steel-smelting
      at the Karaganda Metallurgy Plant. It was found that the workers of the main
      occupational groups at the plant were insufficiently provided with vitamins A, C
      and B due to their low content in the food. The system of medico-prophylactic
      vitamin administration used for steel workers is ineffective.

PMID- 1387489
TI  - Koala lymphoid cells: analysis of antigen-specific responses.
AB  - Bovine serum albumin (BSA) and ovine immunoglobulin (OvIgG) were used to induce
      humoral immune responses in two koalas which were also painted with 2-4
      dinitrofluorobenzene (DNFB) and subsequently tested for local delayed-type
      hypersensitivity (DTH) reactions. The responses observed support the suggestion
      that the koala is 'immunologically lazy'. Antibody responses to BSA and OvIgG
      were not detected until 12 weeks after the initial antigen injection and antigen
      specific in vitro proliferative responses by the mononuclear cells (PMC) of
      immunised animals could not be induced, although these cells did respond to
      concanavalin A and phytohaemagglutinin. Similarly, DTH responses to DNFB could be
      elicited in vivo, but took a relatively long time to develop and the PMC of the
      sensitised koalas were unresponsive to the sensitising antigen in vitro. The
      absence of proliferation when mixed suspensions of PMC from different koalas were
      cultured in vitro is consistent with these results.

PMID- 1387491
TI  - [Actual nutrition and health of several groups of rural and urban population of
      the Republic of Georgia].
AB  - The results of the study have shown that the nutrition of rural population is
      characterized by excessive consumption of bread and baked products, by high
      content of phosphorus, magnesium and iron, low content of animal proteins,
      vegetable oils, calcium, vitamins A, ascorbic acid and riboflavin. The incidence
      of cardiovascular, respiratory and alimentary diseases in this group of
      population was rather high. The nutrition of students is characterized by
      excessive consumption of polysaccharides, vegetable oils, thiamine, niacin,
      ascorbic acid (in winter-spring period), and calcium. Diseases associated with
      nutrition disorders (obesity, hepatitis, cholecystitis, colitis) are most often
      recorded in this group of population.

PMID- 1387492
TI  - [Effects of docosahexaenoic and eicosapentaenoic acids on the state of
      metabolites of the prostacyclin I2--thromboxane A2 system in streptozotocin
      diabetes mellitus].
AB  - Data are presented on the level of stable metabolites of prostacyclin I2
      thromboxane A2 system in streptozotocin diabetes mellitus in rats. It is shown
      that simulation of streptozotocin diabetes mellitus leads to the reduction of 6
      ketoprostaglandin F1 alpha content in the aortal wall tissue and blood plasma,
      and to a rise of thromboxane B2 level and the thromboxane B2/6-ketoprostaglandin
      F1 alpha ratio in the blood plasma. Inclusion of docosahexaenic and
      eicosapentaenic acid concentrate into the ration of animals with streptozotocin
      diabetes mellitus is conducive to normalization of the stable metabolite level in
      the prostacyclin I2-thromboxane A2 system.

PMID- 1387493
TI  - [Determination of N'methylnicotinamide and nicotine coenzymes in biological in
      biological media by the fluorescent method].
AB  - Assay of N1-MNA was conducted in 96 urine samples using two methodological
      variants with external and internal N1-MNA standards. Basing on significant
      fluctuations of the percent of detecting N1-MNA added to urine, the necessity of
      using the internal standard was proved. A significant (up to 30%) overestimating
      of the values in using the external standard makes difficult revealing niacin
      deficiency. It has been recommended that NAD preparation be used as an internal
      standard in NAD + NADP assay in the blood, that permits one to simplify
      significantly the counting and to avoid the universal coefficient (used in
      literature) of recalculating N1-MNA fluorescence to nicotinamide coenzyme
      fluorescence because this coefficient is not a constant value.

PMID- 1387494
TI  - [Effects of the use of a multivitamin preparation "Pikovit" (KRKA, Yugoslavia) on
      providing nursery children with vitamins].
AB  - Providing of children aged 3-5 years with vitamins C, B1, B2, B6 and PP was
      studied before and after intake (during 3 months) of multivitamin "Pikovit"
      (KRKA, Yugoslavia) by the excretion with urine of ascorbic acid, thiamine,
      riboflavin, 4-pyridoxic acid and N-methylnicotinamide. Before "Pikovit" intake
      the mean level of thiamine excretion was close to the lower border of the normal
      level, while ascorbic acid and N-methylnicotinamide levels were lower than the
      normal in 73 and 69% of the children studied, respectively. "Pikovit" induced an
      increase in the mean values of excretion of all vitamins studied except for
      ascorbic acid. The multivitamin prevented the impairment of children providing
      with vitamins C and B6, and improved their provision with vitamins B1, B2 and PP.
      However, the doses of vitamins used proved to be insufficient for complete
      normalization of the vitamin status in children, therefore it is necessary to use
      "Pikovit" in higher doses as it is recommended by the firm-manufacturer.

PMID- 1387495
TI  - [Evaluation of the effectiveness of a new multivitamin preparation for children
      1.5 to 6 years of age in Baku institutions].

PMID- 1387497
TI  - [Provision of vitamins for school children and ways of its optimization].

PMID- 1387496
TI  - [Results of prophylactic vitamin administration of schoolchildren in Tbilisi].
AB  - The data are presented on providing with vitamins of schoolchildren in Tbilisi.
      Significant disorders were revealed in their providing with vitamins due to
      insufficient content of vitamins in daily food rations of the schoolchildren
      investigated. To correct their vitamin status an additional vitamin
      administration to schoolchildren with the multivitamin compound "Hexavitum" was
      conducted and its positive effect on the parameters of their physical and mental
      development was recorded.

PMID- 1387498
TI  - [Immediate and late results following endarterectomy of the carotid bifurcation].
AB  - In a retrospective study we analysed two groups each consisting of 100
      consecutive patients of similar age and sex distribution who underwent surgery
      for carotid disease with an intervening period of 5 years (group A 1980/82, group
      B 1986/87) between the collectives. Against a background of changing indications,
      tactics and techniques the aim of the study was to detect any differences between
      the two groups. Group A had a higher proportion of coronary and peripheral
      vascular disease. The states of cerebral ischemia I, II and III were distributed
      equally, but state IV was seen more frequently in group B (p less than 0.05). The
      number of shunt/without shunt operations in group A was 97/2, in group B 10/84 (p
      less than 0.005). The external carotid artery was deobliterated in 58/81 cases
      group A versus group B (p less than 0.005). We closed the artery by direct suture
      in 8/31 (p less than 0.005), by autologous venous patch in 53/26 (p less than
      0.005) and by Dacron patches in 39/41 patients. In group A the operative
      mortality was zero and in group B 1 patient died; one patient in group B
      developed sudden occlusion (with TIA) postoperatively. Transient intra
      /postoperative neurological deficits occurred in 1/2, permanent in 4/2 patients
      (n.s.). 54/25 patients have died up to 31/08/91. Coronary heart disease was the
      main cause of late complications and deaths in group A (p less than 0.025).
      Statistically, there was no dependence of neurological deficits on group, sex,
      age or intraoperative management. Only patients with preoperative PRINDS hat a
      higher postoperative neurological deficit rate than the others.

PMID- 1387499
TI  - [Decreased blood pressure in sleep and left ventricular hypertrophy in patients
      with kidney transplants].
AB  - Since left-ventricular hypertrophy (LVH) has been identified as a poor prognostic
      indicator in patients with secondary hypertension, we investigated 38 renal
      transplant recipients on antihypertensive medication with 24-h ambulatory blood
      pressure measurement (SpaceLabs 90207) and determined their left-ventricular mass
      by two-dimensional guided M-mode echocardiography. An increased left-ventricular
      mass correlated with a reduced fall of diastolic blood pressure during sleep (r =
      0.29; p less than 0.05), as well as with a reduced fall of mean arterial pressure
      during sleep (r = 0.31; p less than 0.05). Therefore, a less pronounced afterload
      during sleep is related to more severe left-ventricular hypertrophy, suggesting a
      worse cardiovascular prognosis.

PMID- 1387501
TI  - Mutations in phosphofructokinases alter the control characteristics of glycolysis
      in vivo in Saccharomyces cerevisiae.
AB  - Ethanol and CO2 production from glucose by non-proliferating suspensions of
      aerobically-grown, glucose-derepressed wild-type Saccharomyces cerevisiae is
      inhibited by O2; monitoring by mass spectrometry provides a direct method for
      measurement of the Pasteur effect. Under aerobic conditions, that part of the CO2
      evolved equivalent to the O2 consumed, is produced by respiration: subtraction of
      this respiratory CO2 from the total gives CO2 produced by aerobic glycolysis.
      Pasteur quotients (anaerobic CO2/aerobic glycolytic CO2) were within the range
      1.2 to 3.0. The Pasteur effect was not observed in the presence of carbonyl
      cyanide m-chlorophenylhydrazone, an uncoupler of mitochondrial energy metabolism,
      or in a rho degree cytoplasmic petite mutant. A 'non-allosteric' mutant with an
      altered regulatory subunit of phosphofructokinase showed no Pasteur effect.
      Strains bearing a nonsense mutation pfk1 in the catalytic subunit of soluble
      phosphofructokinase (PFKI) also showed no Pasteur effect; the residual
      fermentative activity of this strain was dependent on PFKII, the particulate
      phosphofructokinase. A double mutant lacking both PFKI and glucose-6-phosphate
      dehydrogenase showed similar characteristics to those of the single pfk1 mutant;
      this indicates that the hexose monophosphate shunt is not acting to bypass the
      phosphofructokinase block. A 'hyper-allosteric' mutant altered in the regulatory
      subunit encoded by the gene PFK2 showed characteristics of glucose fermentation
      and ethanol oxidation very similar to those of wild-type organisms. These results
      indicate that either of the two phosphofructokinases can carry out glycolysis.

PMID- 1387500
TI  - [Long-term blood pressure measurement for evaluating the first dose response of
      captopril and ramipril in patients with a stimulated renin system].
AB  - First-dose-response of captopril 1 x 25 mg (no prodrug) and ramipril 1 x 2.5 mg
      (prodrug) were compared in two groups of 17 patients with moderate or severe
      hypertension and stimulated renin-angiotensin system (because of continuous
      diuretic therapy) by means of 24-h blood-pressure measurement at the 1st and 7th
      day of therapy. In the ramipril-group the antihypertensive effect started after 2
      h, had its maximum (mean: -13/-8 mmHg) after 4 h and remained unchanged for 8 h.
      The antihypertensive effect was significant for 24 h. There was a slightly but
      not significant improved blood-pressure reduction at the 7th day compared to the
      1st. The captopril-group showed a fast and marked decrease of blood pressure
      within the first hour, and reached its maximum (mean: -18/-10 mmHg) after 2 h.
      After 7 h there was no antihypertensive effect detectable. At the 7th day blood
      pressure reduction was less pronounced compared to the 1st day. The results show
      that initial decrease of blood pressure in risk-patients is less severe with
      prodrug-ACE-inhibitors with slow onset of action so that counterregulation can be
      activated and prevent severe, fast, ACE-inhibitor-induced hypotension. 24-h-blood
      pressure measurement is a sufficient method to evaluate first-dose-response of
      ACE-inhibitors.

PMID- 1387502
TI  - Ketones in resin composites. Effect of ketone content and monomer composition on
      selected mechanical properties.
AB  - To optimize the improvements by diketones of the mechanical properties of resin
      composites, diacetyl was added to two different monomer mixtures in different
      quantities. There was a positive correlation between content of diacetyl and
      tensile strength, flexural strength, and modulus of elasticity, respectively, of
      both the BISGMA/TEGDMA- and the UEDMA/HEMA-based materials. Addition of diacetyl
      did not influence the modulus of resilience significantly. Addition of diacetyl
      resulted in increases in mechanical properties which were of the same relative
      size for BISGMA/TEGMA-based materials as for UEDMA/HEMA-based materials. However,
      because of higher control values, except for modulus of elasticity, the
      properties of UEDMA/HEMA-based composites were superior to those of the
      BIGSMA/TEGDMA-based materials. A content of approximately 24 mole% diacetyl
      seemed to have optimum effect on mechanical properties, giving a mean increase of
      25% in tensile strength, flexural strength, and modulus of elasticity.

PMID- 1387503
TI  - Is vascular angiopathy following intracranial aneurysm rupture immunologically
      mediated?
AB  - Immunofluorescence studies showed the presence of IgM and/or C3 in the
      endothelium of intracranial aneurysms in 5 out of 6 patients with subarachnoid
      haemorrhage (SAH). In none of them were the immune deposits found in the gyrus
      rectus. Cortical tissue of 4 epileptic patients which served as a control give
      negative results. Serum studies on femoral artery wall used as an antigenic
      substrate did not reveal circulating antibodies of the IgM or IgG class. Our
      studies strongly suggest that the IgM and/or C3 immune deposits located in the
      endothelium of intracranial arteries may play a role in post SAH neurological
      complications.

PMID- 1387504
TI  - Unilateral swelling of the lower abdominal wall. Unusual clinical manifestation
      of an upper lumbar disc herniation.
AB  - Circumscribed unilateral paralysis of abdominal muscles is a rare clinical
      feature and has previously been described in diabetic neuropathies and traumatic
      or non-traumatic compressive neuropathies. The paper describes a case presenting
      with transversus abdominis muscle paralysis and burning paraesthesia in the
      anterolateral aspect of the thigh caused by a lateral L2-L3 disc herniation.
      Abdominal echography and the EMG investigation led to the suspicion of a disc
      prolapse which was eventually verified by myelography completed with a CT scan.
      Surgery confirmed L2 root compression by a large calcified herniation in the
      intervertebral foramen L2-L3. The anatomical principles are recalled to explain
      the clinical manifestations.

PMID- 1387505
TI  - Cardiovascular complications of cocaine abuse.
AB  - Cocaine abuse may lead to serious cardiac complications, including myocardial
      ischemia and infarction, myocarditis, cardiomyopathy and arrhythmias. With
      concomitant use of alcohol and cocaine, cocaethylene is produced by hepatic
      transformation. Cocaethylene is now thought to be primarily responsible for the
      deaths that occur among cocaine abusers. Treatment of cardiovascular
      complications focuses on cocaine-induced ischemia, hypertension and arrhythmias.
      The use of thrombolytic agents in myocardial infarction remains controversial.
      Concurrent detoxification with bromocriptine and norepinephrine is recommended.

PMID- 1387506
TI  - Effects of amlodipine on myocardial infarction, infarct expansion, and
      ventricular geometry in the rat.
AB  - Infarct expansion remains an important sequela of myocardial infarction. Both
      angiotensin converting enzyme inhibitors and intravenous nitrates reduce early
      infarct expansion in humans. This is believed to be caused by the reduction in
      left ventricular systolic wall stress that results from the arteriolar
      vasodilatation they produce. Patients are frequently already receiving calcium
      channel blockers at the time of infarction or these drugs are sometimes
      administered in the perimyocardial infarction period. The calcium blockers of the
      dihydropyridine class might be expected to modify infarct expansion. However,
      their effect on this process has not been studied. We therefore evaluated the
      effect of early treatment with the calcium blocker amlodipine, a potent
      arteriolar vasodilator with minimal negative inotropic properties, on chronic
      myocardial infarction in the rat. Permanent left coronary occlusion was created
      after pretreatment with amlodipine, 0.25 mg/kg (low dose) or 1.0 mg/kg (high
      dose), or placebo, intravenously twice a day, and continued for 7 days after
      infarction. Hearts (n = 50) were perfusion fixed 21 days after infarction and
      analyzed for infarct extent, scar thickness, left ventricular shape and size, and
      expansion index. Both doses decreased mean blood pressure (119 +/- 3 to 99 +/- 5
      mm Hg low dose, p = 0.004; 110 +/- 5 to 84 +/- 4 mm Hg high dose, p = 0.0003),
      with reflex tachycardia only after the high dose (heart rate 395 +/- 9 to 434 +/-
      11, p = 0.001). Infarct extent was equal in the three groups (39 +/- 2%, 41 +/-
      2%, and 41 +/- 3% of left ventricular circumference for control, low, and high
      doses, respectively). The three groups did not differ significantly with regard
      to left ventricular cavity cross-sectional area (80 +/- 4, 77 +/- 3, and 87 +/- 3
      mm2, control, low, and high doses, respectively; p = 0.07 high dose vs control),
      mean scar thickness (0.74 +/- 0.06, 0.73 +/- 0.05, and 0.65 +/- 0.06 mm, control,
      low, and high doses, respectively; p = NS), and expansion index (1.52 +/- 0.10,
      1.58 +/- 0.12, and 1.95 +/- 0.19, control, low, and high doses, respectively; p =
      0.08 high dose vs control). In the subgroup with larger infarcts (infarct extent
      greater than 0.39 of left ventricle), the expansion index was higher in the high
      dose group (2.37 +/- 0.23 vs 1.64 +/- 0.17 control; p = 0.04). In this model,
      treatment with amlodipine does not limit infarct extent or reduce early infarct
      expansion and left ventricular dilatation, even when initiated before
      infarction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1387507
TI  - Effect of captopril on the prevention and regression of myocardial cell
      hypertrophy and interstitial fibrosis in pressure overload cardiac hypertrophy.
AB  - This article reports on the effects of captopril on both the prevention and the
      regression of myocardial cell hypertrophy and interstitial fibrosis in
      experimental animals (rats) with pressure overloaded hearts. Constriction of the
      abdominal aorta just below the diaphragm during periods of 20 days (prevention
      experiment) and 40 days (regression experiment) resulted in hypertension and
      cardiac hypertrophy. In the prevention experiment, captopril was able to inhibit
      the development of high blood pressure levels and cardiac hypertrophy in aortic
      constricted rats. Similarly, the treatment of sham-operated rats with captopril
      led to a reduction in the weight of the heart and in the myocyte diameter
      compared with controls. The myocyte volume fraction of the left ventricles of
      both aortic-constricted and sham-operated animals that were treated with
      captopril was significantly diminished compared with that of the control group.
      The interstitial collagen volume fraction of all experimental groups was elevated
      as compared with the control group. As a consequence, the ratios of myocytes to
      interstitial collagen in groups of aortic-constricted rats, aortic-constricted
      rats that were treated with captopril, and sham-operated rats that were treated
      with captopril were reduced compared with the control group; that is, although
      captopril was able to prevent myocardial cell hypertrophy after aortic
      constriction, it could not prevent the maintenance of a normal ratio of myocytes
      to interstitial collagen, which was due to increased collagen volume fraction. In
      the regression experiment, captopril lowered high blood pressure levels and
      augmented heart weights to control values. The mean myocyte transverse diameter
      in aortic-constricted rats that were treated with captopril was significantly
      smaller than that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387508
TI  - Syringomas in Down syndrome.

PMID- 1387509
TI  - The classroom as clinic: applications for a method of teaching clinical
      reasoning.
AB  - This study examined the efficacy of one method for teaching diagnostic reasoning
      to occupational therapy students. During a clinical reasoning seminar in their
      first academic year, 80 entry-level occupational therapy master's degree students
      in three successive classes were given three different levels of exposure to
      classroom-as-clinic or in-class evaluations of adults with physical or
      psychosocial disabilities. During the following summer, most students completed
      their first Level II fieldwork experience. Students' grades for a second-year
      classroom-as-clinic experience with adults with physical disabilities were then
      compared across groups to determine the relative effect of the different seminar
      formats and fieldwork experiences. Students who had experienced in-class
      evaluations during their first academic year wrote significantly more accurate
      second-year evaluations than those who had not. Students who had completed
      psychosocial Level II fieldwork experiences were as accurate on their evaluations
      as students who had had physical dysfunction fieldwork experiences. The results
      suggest that in-class evaluations improve students' diagnostic reasoning skills.

PMID- 1387510
TI  - Dehydroepiandrosterone prevents dexamethasone-induced hypertension in rats.
AB  - Dehydroepiandrosterone (DHEA) is an endogenous steroid having a wide variety of
      biological and biochemical effects. In the present study, we have examined the
      role of DHEA on various rodent models of experimental hypertension. Sprague
      Dawley rats were given subcutaneous injections of 1.5 mg dexamethasone every
      alternate day, resulting in an increase in systolic blood pressure within 1 wk.
      Interestingly, administration of a pharmacological dose of 1.5, 3, or 7.5 mg DHEA
      along with dexamethasone prevented dexamethasone-induced hypertension in a dose
      dependent manner. DHEA had no effect on the hypertension induced by
      deoxycorticosterone acetate (DOCA)-salt administration using uninephrectomized
      rats or on the genetic model of spontaneously hypertensive rats. Dexamethasone
      administration resulted in a significant weight loss in rats, which was not
      prevented by simultaneous administration of DHEA. These results indicate that
      dexamethasone-mediated weight loss may involve mechanisms separate from its
      hypertensive action. Dexamethasone treatment resulted in a significant decrease
      in food consumption that was not reversed by DHEA. It is concluded that DHEA at
      doses above physiological levels when given subcutaneously has no effect on DOCA
      salt or a genetic model of hypertension but has a beneficial effect on
      dexamethasone-induced hypertension.

PMID- 1387512
TI  - Bronchodilating effect of ipratropium bromide inhalation powder and aerosol in
      children and adolescents with stable bronchial asthma.
AB  - The purpose of this study was to compare the bronchodilating effect of
      ipratropium bromide (IB) administered by a conventional Ingelheim powder device
      system (IPI) and by a metered dose inhaler (MDI) in children and adolescents with
      stable bronchial asthma. Seventy patients, aged 7 to 16 years, with stable
      bronchial asthma from our outpatient clinic were tested for bronchial
      responsiveness to inhaled IB. Fifteen (21%) of the 70 subjects were found to have
      a substantial bronchial response to inhalation of 40 micrograms IB, i.e. at least
      15% increase in FEV1 30 min after inhalation; the remaining 55 subjects had less
      than 15% increase in FEV1. No relationship between severity of asthma, age or sex
      and bronchial responsiveness to inhaled IB was found. Among the 15 subjects who
      had substantial bronchial response to IB, the increase in FEV1 after inhalation
      of fenoterol tended to be greater than the response to inhaled IB, although this
      did not reach statistical significance. Responders, i.e. subjects who had at
      least 15% increase in FEV1 after inhalation of IB, took part in a double-blind,
      cross-over study of the bronchodilating effect of 40 micrograms IB delivered by
      IPI and MDI. We found no significant differences in the bronchodilating effect
      during a 6-h follow-up. Maximum bronchodilating effect of IB was reached after 30
      min and the maximum response lasted for 90 min. No side or adverse effects were
      observed following inhalation of IB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387511
TI  - Generation of the neutrophil-activating peptide-2 by cathepsin G and cathepsin G
      treated human platelets.
AB  - The neutrophil-activating peptide-2 (NAP-2) is a cytokine that is generated by
      the proteolytic cleavage of a precursor protein and that causes neutrophil
      degranulation and chemotaxis. NAP-2 precursors are produced in platelets and are
      normally found in the circulation. We showed that NAP-2 is generated by the
      action of neutrophil cathepsin G on two of the precursors, the connective tissue
      activating peptide-III (CTAP-III) and beta-thromboglobulin (beta-TG). However,
      neutrophil elastase degraded the precursors to inactive peptides. The specific
      binding of cathepsin G to platelets caused the platelets to secrete NAP-2, and
      cathepsin G bound to the platelets could still generate NAP-2 from its precursor
      proteins. In addition, activated neutrophils in the presence of platelets
      generated NAP-2 from its precursors and caused platelets to secrete NAP-2. These
      studies demonstrate a unique mechanism for the activation of neutrophils through
      the interaction of neutrophils, platelets, and NAP-2 precursors that are released
      either by activated platelets or are present in circulation. It is therefore
      possible that NAP-2 may be generated at sites where aggregations of neutrophils
      and platelets occur in vessels such as pulmonary capillaries in patients with the
      adult respiratory distress syndrome and coronary arteries in patients with
      evolving myocardial infarctions.

PMID- 1387514
TI  - Assessment of acute myocardial infarction by nuclear imaging techniques.
AB  - In recent years, nuclear cardiology techniques have been successfully applied in
      patients with acute myocardial infarction. These scintigraphic measurements have
      provided important diagnostic, therapeutic, and prognostic information based on
      the extent of myocardial damage and the functional reserve of the left ventricle.
      In particular, in the thrombolytic era, myocardial perfusion imaging and
      radionuclide angiography have been shown to be valuable methods for studying the
      effects of reperfusion on the extent of myocardial damage. Nuclear magnetic
      resonance imaging, preferably with contrast enhancement, is one of the newly
      developed nuclear imaging techniques that have probably the greatest potential in
      accurately delineating myocardial infarct size and in evaluating left ventricular
      function. Radionuclide procedures, on the other hand, employ more biologically
      oriented tracers and are therefore capable of monitoring biochemical changes in
      the course of acute myocardial infarction.

PMID- 1387515
TI  - Leber congenital amaurosis in an infant with Down syndrome.
AB  - A male infant had defects of atrial and ventricular septa and trisomy 21. At 2
      months of age, the patient had markedly sluggish pupillary reactions to light OU.
      Searching nystagmus, multiple chorioretinal atrophic spots in mottled retinas,
      and unrecordable electroretinograms also were found in the patient when he was 6
      months of age. We believe that this infant represents a rare case of Leber
      congenital amaurosis in association with Down syndrome.

PMID- 1387513
TI  - The avian muscle spindle.
AB  - The literature on the morphology and physiology of the avian muscle spindle is
      reviewed, with emphasis placed on the period from 1960 to 1991. Traits similar to
      or different from mammalian spindles are recognized. Apart from receptors with
      low intrafusal fiber counts, bird spindles contain two or three types of
      intrafusal fiber. Unlike that of mammals, the equatorial fiber structure in birds
      does not lend itself to classification into nuclear bag and nuclear chain types.
      Avian intrafusal fibers are separable into types based on differences in myosin
      heavy chain composition and motor innervation, but apportionment of these fiber
      types to individual spindles is more variable in birds than in mammals. There is
      morphological evidence in birds for the existence of both gamma and beta
      innervation; however, confirmation of these systems by physiological experiments
      is at best sketchy. A general lack of physiological data is currently the
      greatest drawback to a better understanding of how the avian receptor works, and
      what role it plays in sensorimotor integration.

PMID- 1387516
TI  - Effect of blood transfusion on recurrence of head and neck carcinoma.
      Retrospective review and meta-analysis.
AB  - To study the effect of transfusion on recurrence of squamous cell carcinoma of
      the head and neck, we analyzed the records of 143 patients with stage II through
      IV squamous cell carcinoma of the supraglottic larynx or hypopharynx for whom
      follow-up to recurrence or 5 years after surgical therapy was available.
      Variables studied were age, gender, TNM staging, duration of operation, estimated
      blood loss, units of blood products transfused, surgical margins, number of
      pathologic nodes, radiotherapy, chemotherapy, hematocrit, and serum albumin.
      Multivariate logistic regression demonstrated that transfusion, number of
      pathologic nodes, and preoperative hematocrit were significantly related to
      recurrence. The univariate odds ratio for tumor recurrence in patients receiving
      any blood products was 3.2 (95% confidence interval 1.5 to 6.9; p = .004). Based
      on a meta-analysis of the data from this study and the five published studies,
      the combined odds ratio for recurrence after transfusion was 2.6 (95% confidence
      interval 1.9 to 3.7; p less than .0001). These data identify a clinically
      important adverse effect of transfusion of blood products on tumor recurrence in
      patients with advanced head and neck cancer. We recommend a policy of blood
      conservation surgery to enhance cancer control, and we encourage further research
      to clarify the mechanism(s) of this effect.

PMID- 1387517
TI  - GAP-43 gene expression is increased in anterior horn cells of amyotrophic lateral
      sclerosis.
AB  - In amyotrophic lateral sclerosis (ALS), neuronal loss and axonal degeneration
      occur in motor neurons. Although there is limited axonal regeneration, surviving
      motor neurons send collateral sprouts to denervated muscle fibers. GAP-43, a
      protein enriched in growth cones and synaptic terminals, is thought to have a
      role in axonal elongation and synaptogenesis. GAP-43 messenger RNA (mRNA)
      expression was evaluated in ALS spinal cords using Northern blot analysis and in
      situ hybridization to assess whether surviving neurons can mount an appropriate
      response to injury. There was a two- to four-fold increase in GAP-43 mRNA in ALS
      that localized to the anterior horn cells. The increase in GAP-43 mRNA indicates
      that the mechanism which leads to degeneration in ALS does not compromise the
      neuron's capacity for vigorous expression of growth-associated proteins.

PMID- 1387518
TI  - [Antibiotic sensitivity and pathogenetic factors of hospital strains of
      Pseudomonas aeruginosa isolated from patients treated in a resuscitation unit].
AB  - Strains of Pseudomonas aeruginosa were isolated from patients treated in the
      Centre of Thermal Affections in 1985-1989. It was shown that 72.9, 59.3, 33.8 and
      54.2 per cent of the isolates were sensitive to cefotaxime, tobramycin,
      gentamicin and polymyxin, respectively. The study of pathogenicity factors of the
      isolates revealed that 83 per cent of the strains produced thermolabile
      enterotoxin, 79.6 per cent of the strains had adhesive activity and 71.1 per cent
      of the strains produced hemolysin. The study detected combinations of various
      pathogenicity factors. 42.3 per cent of the isolates had both adhesive and
      enterotoxigenic properties. Adhesiveness and hemolytic activity were shown by
      13.5 per cent of the strains. 16.9 per cent of the strains produced both
      enterotoxin and hemolysin. Adhesive activity, enterotoxigenicity and hemolysin
      production were observed in 6.7 per cent of the strains. It was noted that the
      strains of P. aeruginosa resistant to polymyxin mainly produced enterotoxin (18.6
      per cent) and those resistant to cefotaxime had adhesive activity (34.0 per
      cent).

PMID- 1387519
TI  - [Antibiotic sensitivity of Vibrio cholerae 01 isolated from environmental
      objects].
AB  - The sensitivity of 252 Vibrio cholerae-O1 strains isolated from environmental
      objects to antibiotics of various groups was assayed by the method of serial
      dilutions on solid media. The biological characteristics of the isolates are
      presented. The Vibrio cholerae isolates with serological variation were the most
      frequent (36.6 per cent), so are the cultures detected by their sensitivity to
      the specific phages (87.5 per cent). It was found that changes in some biological
      properties of the strains did not coincide with the changes in the antibiotic
      sensitivity. The isolates were highly sensitive to tetracycline, chloramphenicol,
      gentamicin, erythromycin and rifampicin and less sensitive to novobiocin and the
      other aminoglycosides. The sensitivity to the beta-lactams was the lowest. The
      resistance determinants were detected in single strains (6.3 per cent), the
      kanamycin and novobiocin resistance determinants being detected in 15 out of the
      16 strains tested. The study showed that the cultures of Vibrio cholerae-O1
      isolated from the environmental objects generally preserved their sensitivity to
      the diverse group antibiotics.

PMID- 1387520
TI  - [Study of the immunosuppressive effect of cyclosporine in experimental studies].
AB  - Specific immunosuppressive activity of cyclosporine prepared at the National
      Research Centre of Antibiotics by using its original producing culture was
      studied. It inhibited basic cellular immune responses such as DTH and transplant
      vs. host and prolonged the lifespan of tumor xenografts under the kidney capsule.
      Cyclosporine also suppressed the humoral immunity. Its inhibitory effect on
      lymphocyte blast transformation induced by lectins and in mixed lymphocyte
      cultures was shown in vitro. Cyclosporine inhibited activity of natural killer
      cells and T-suppressor cells induced by concanavalin A. It was demonstrated on
      the models of skin allotransplantation in mice and heterotopic transplantation of
      the heart in rats that cyclosporine prolonged the transplant lifespan. By the
      main indices of the cellular immunity and in the models of the transplantation
      immunity, cyclosporine prepared at the National Research Centre of Antibiotics
      was shown to be similar to that manufactured by Sandoz.

PMID- 1387521
TI  - Facet joint block for low back pain: identifying predictors of a good response.
AB  - This preliminary study was conducted to identify a facet joint syndrome in low
      back pain. Ninety maneuvers and symptoms were compared between patients relieved
      (responders) and those unrelieved (nonresponders) after intraarticular blocks.
      Fifty-one patients participated in the study; 11 were excluded from evaluation
      because of unsuccessful injection into the joints as planned. Of the 40 patients
      included, 20 had four joints anesthetized, 16 had two joints anesthetized, and
      four had three joints anesthetized. Twenty-two were responders, 17 of whom had
      more than 90% relief of pain. Only a few variables were more frequent in the
      responder group: older age, absence of exacerbation by coughing, relief when
      recumbent, absence of exacerbation by forward flexion and when raising from this
      flexion, absence of worsening by hyperextension, and extension-rotation. When
      four of these seven variables were present in the same patient, sensitivity was
      81.8% and specificity 77.8%, but this discriminant power must be evaluated in a
      new population.

PMID- 1387522
TI  - Isokinetic arm and leg strength of adults with Down syndrome: a comparative
      study.
AB  - This study compared isokinetic arm (elbow flexion and extension) and leg (knee
      flexion and extension) strength of individuals with Down syndrome (DS), with
      mental retardation without DS (NDS), and sedentary young adults with no mental
      retardation (NMR). Eighteen individuals with DS, NDS, and NMR (11 men and seven
      women in each group) performed strength tests on a Cybex 340 isokinetic
      dynamometer. Parameters measured were peak torque (ft/lb), peak torque percent
      body weight (%BW), average power (watts), and average power %BW. Subjects with
      mental retardation (ie, DS and NDS groups) performed the test on two separate
      days with best test results chosen for statistical comparisons. The NMR group
      performed the test once. In all isokinetic strength parameters measured for arm
      strength, the NMR group demonstrated significantly higher scores than subjects
      with DS and NDS. Subjects with DS and NDS displayed similar test results.
      Similarly, for all the isokinetic strength parameters measured for leg strength,
      NMR demonstrated significantly higher scores than subjects with DS and NDS.
      Subjects with NDS, however, averaged significantly higher test results than
      subjects with DS for leg strength. The results of this study indicate that both
      subject populations who were mentally retarded exhibited lower arm and leg
      strength than the NMR subjects. Additionally, subjects with DS demonstrated
      inferior leg strength when compared to their peers with NDS.

PMID- 1387523
TI  - Predicting life satisfaction among adults with physical disabilities.
AB  - The perceptions of life satisfaction among adults with physical disabilities were
      examined in this research. Personal interviews were conducted with 790 adults who
      had a physical disability. Data were collected using the Center for
      Epidemiological Studies Depression Scale, Rosenberg's Self-esteem Scale, and the
      Life 3 Scale. Results from a stepwise multiple regression analysis (n = 344)
      indicated that leisure satisfaction was the most significant predictor of life
      satisfaction, explaining 42% of the variance in the life satisfaction scores for
      this population. An additional 11% of the variance in life satisfaction was
      explained by scores on financial status, self-esteem, health satisfaction,
      religious satisfaction, and marital status. Findings from this research highlight
      the role that leisure satisfaction plays in enhancing life satisfaction among
      individuals with physical disabilities. Furthermore, the findings suggest that
      leisure and life satisfaction levels are influenced by employment status and
      whether the disability was acquired. Discussion centers on the potential
      contribution that therapeutic recreation can have in the rehabilitation arena.

PMID- 1387524
TI  - Therapeutic exercise in chronic neck and back pain.
AB  - Research regarding the effect of exercise on chronic benign axial pain is
      reviewed. Both chronic low back pain (LBP) and chronic neck pain are associated
      with weakness of the trunk and neck musculature; however, it is unknown whether
      weakness is a cause or effect. The relationship between incoordination of the
      neck or trunk musculature and chronic pain is unclear. Exercise is associated
      with improved strength and endurance and decreased pain in subjects with LBP but
      the literature is very sparse with respect to chronic neck pain. Range-of-motion
      is also diminished in those with LBP and improves with exercise, and is
      associated with abatement in symptoms. No evidence could be found regarding the
      effect of exercise on segmental motion. Exercise is also associated with improved
      function, however the mechanism whereby either pain report or function improves
      is unclear. A greater understanding of the role of exercise will require more
      specific studies of strength, coordination, motion, function, and pain.

PMID- 1387525
TI  - Surgical treatment of enteric 'bud' fistulas in contaminated wounds. A riskless
      extraperitoneal method using split-thickness skin grafts.
AB  - We describe methods and results of a local extraperitoneal method of repairing
      enterocutaneous "bud" fistulas in abdominal-wall defects. The method is performed
      with local anesthesia and involves an extraperitoneal closure with skin-graft
      coverage. Of the nine fistulas so treated, five healed. No patient's
      postoperative course was set back by the repairs that failed since the method
      precludes intraperitoneal entrance. Two of three high-output fistulas were
      successfully repaired with the extraperitoneal method, reversing an otherwise
      stormy clinical course. We conclude that for epithelialized enterocutaneous
      fistulas, little is lost if our method of repair fails and much is gained if it
      is successful in these critically ill patients.

PMID- 1387526
TI  - Implantable programmable insulin pumps for the treatment of diabetes.
AB  - Implantable programmable pump systems for insulin delivery to the peritoneal
      cavity or for intravenous insulin delivery have been recently developed. Thirty
      one pumps were implanted in 25 patients between 1987 and 1991. At this writing,
      76% of patients had functioning pumps. Ninety-two percent of pumps were
      functioning at 1 year; 89% at 2 years; and 50% at 3 years. No life-threatening
      complications, either surgical or metabolic, developed. However, 18 patients
      required 23 outpatient procedures for maintenance of pump function or for pump
      removal. Metabolic improvement was evidenced by mean and standard deviation of
      blood glucose levels and by glycosylated hemoglobin levels.

PMID- 1387527
TI  - Anatomic and clinical considerations of an internal mammary artery harvest.
AB  - In an effort to understand the perceived correlation of internal mammary artery
      harvesting and wound healing difficulties in the inferior margins of the
      sternotomy incision, we showed the cutaneous vascular perfusion in the sternal
      and xiphoid areas by India ink injection studies in cadavers. With these studies,
      we demonstrated an inherent paucity of nutrient supply to the inferior sternum
      and xiphoid area. The classic internal mammary artery harvest further compromises
      the blood supply to these areas. We believe that limiting the most inferior
      dissection of the internal mammary artery and not including the distal
      bifurcation leaves intact the lateral musculophrenic nutrient supply to the
      inferior sternum and xiphoid area and to the ipsilateral abdominal rectus muscle.
      These guidelines will help to prevent ischemic complications of this area and may
      aid in reconstruction. If the bifurcation is harvested, we believe that the
      removal of the avascular xiphoid cartilage at the time of the initial bypass
      procedure may eliminate this as a potential septic focus.

PMID- 1387529
TI  - Percutaneous transluminal angioplasty in transplant renal arterial stenoses: a
      long-term follow-up.
AB  - Transplant renal artery stenosis is a potentially treatable cause of post
      transplant hypertension. Transluminal angioplasty under radiological control
      facilitates treatment, and in this study the results of 15 consecutive patients
      treated in one department have been analysed to assess the safety and success of
      the technique, blood pressure control and transplant function. Technical success
      was achieved in 14 patients (93%), with zero mortality and only 1 major
      complication requiring surgical intervention. Blood pressure control was
      significantly improved by angioplasty, mean blood pressure (diastolic + 1/3 pulse
      pressure) being lower 4-6 weeks later (P less than 0.05) and a mean of 34 months
      later (P less than 0.01), and transplant renal function was unaffected. In the
      treatment of transplant renal artery stenosis percutaneous transluminal
      angioplasty is effective, safe and often of lasting benefit.

PMID- 1387528
TI  - Unexpected, late cardiovascular effects of surgery for peripheral artery disease.
      Veterans Affairs Cooperative Study 199.
AB  - In reviewing late morbidity of a multicenter clinical trial comparing balloon
      angioplasty (percutaneous transluminal angioplasty) with bypass surgery for lower
      extremity ischemia, an unexpectedly high incidence of adverse systemic events in
      surgical patients was uncovered. The study was prospective and randomized, and
      included a total of 263 patients, with follow-up from 2 to 6 years. When end
      points of related deaths, amputations, and intervention failures were summed,
      surgery was favored over percutaneous transluminal angioplasty at 4 years.
      Progression of cardiac and renal dysfunction and mortality differed between
      groups. A total of 42 deaths were in the group who underwent surgery and 27 in
      those who underwent percutaneous transluminal angioplasty. The percentage
      difference in death rate between the two groups increased each year to reach 10%
      at 5 years. A significant difference in renal function was noted in nine patients
      who underwent surgery and zero who underwent percutaneous transluminal
      angioplasty. Myocardial infarctions were greater on follow-up of surgical
      patients. After 6 years, congestive heart failure had occurred in 19 patients who
      underwent surgery and eight who underwent percutaneous transluminal angioplasty.
      The trends in this study of patients with only moderately severe peripheral
      arterial disease suggest an increased rate of deterioration of cardiac and renal
      function in patients who have arterial operations. In surgical patients,
      mortality was 13.1% per year, whereas it was 8.4% for patients treated with
      percutaneous transluminal angioplasty. Future intervention studies should include
      long-term follow-up of such cardiovascular events.

PMID- 1387530
TI  - In vivo and in vitro mechanisms of cardiac allograft acceptance in the rat after
      short treatment with 15-deoxyspergualin.
AB  - 15-Deoxyspergualin (DSG) has been reported to be a useful immunosuppressive agent
      already used to inhibit acute rejection in clinical transplantation. In the
      present study, the survival of heart allograft in rats after a short course of
      DSG treatment and the mechanisms underlying DSG-induced heart allograft
      acceptance were studied. Male LEW rats were used as recipients. Male ACI and
      Wistar rats were used as donors and third-party donors, respectively. Survival of
      ACI heart grafts in LEW recipients treated with a short course of DSG starting on
      day 4 after grafting was markedly prolonged, with a mean survival time of 16.6 +/
      5.8 days and 29.8 +/- 3.0 days at doses of 2.5 mg/kg per day and 5 mg/kg per
      day, respectively. On day 20 after grafting, the mechanism of inducing allograft
      survival after DSG treatment at a dose of 5 mg/kg per day was analyzed by testing
      the activation of spleen cells or serum in several assay systems. Spleen cells
      from DSG-treated rats with surviving heart allografts showed almost no
      proliferative response against donor strain stimulator cells compared with
      controls. The cytotoxic activity towards donor strain target cells of spleen
      cells from DSG-treated rats with surviving heart allografts was lower than that
      of spleen cells from rats with rejected heart allografts.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1387532
TI  - Foyer-Handicap: a warm, supportive environment.

PMID- 1387531
TI  - Alpha-human-ANP response to preanesthetic volume expansion and subsequent renal
      transplantation in diabetic and nondiabetic uremic patients.
AB  - alpha-Human atrial natriuretic peptide (ANP) concentrations were measured in 11
      diabetic patients with uremia and in 16 nondiabetic uremic controls undergoing
      renal transplantation after preanesthetic volume expansion with 1000 ml saline
      solution within 10 min. Two diabetic and seven nondiabetic patients received
      grafts from living donors and the rest from cadaveric donors. Volume expansion
      induced a significant increase in the cardiac filling pressures (P less than
      0.001), which were kept at that level especially at declamping, which was
      preceded by mannitol infusion. The baseline mixed venous ANP levels were
      significantly higher in the diabetic (252 +/- 6 pg/ml) than in the nondiabetic
      group (103 +/- 14 pg/ml; P less than 0.05). In the nondiabetic group, ANP
      increased to 177 +/- 40 pg/ml as a response to volume loading (P less than 0.05);
      it was not clearly changed in the diabetic group. Arterial ANP increased from 267
      +/- 55 to 343 +/- 75 pg/ml in the diabetic group (P less than 0.05 and from 102
      +/- 17 to 147 +/- 31 pg/ml in the nondiabetic group (P less than 0.05). During
      transplantation, mixed venous ANP decreased to 125 +/- 55 pg/ml in the diabetic
      and to 80 +/- 10 pg/ml in the nondiabetic group (P less than 0.001). About 30% of
      circulating ANP was taken up by the transplant irrespective of postoperative
      graft function. Two patients in each group showed delayed diuresis requiring
      postoperative dialysis therapy (22% of all cadaveric transplantations). ANP
      levels at declamping had no correlation to the outcome of kidney function.

PMID- 1387533
TI  - Families with a handicapped child: dealing with pain.

PMID- 1387534
TI  - Molecular and crystal structure of the hydrochloride monohydrate of (R)-N-[[1-(4
      fluorobenzyl)-2-pyrrolidinyl]methyl]-5-bromo-2,3- dimethoxybenzamide, NCQ 115, a
      novel dopamine D2 receptor antagonist.
AB  - The structure and absolute configuration of the title compound have been
      determined by single crystal X-ray diffraction analysis. The space group symmetry
      is R21; the monoclinic unit cell contains two molecules and has the dimensions a
      = 12.4291(8), b = 7.4511(5), c = 12.7854(7) angstroms and beta = 102.295(7)
      degrees. The planar conformation of the benzamide moiety is stabilized by an
      intramolecular (N)H...O bond. Hydrogen bonds connect the chloride anion to the
      protonated pyrrolidine N atom, and also the crystal water to the carbonyl oxygen
      of the amide group. The molecule has a folded conformation in which the N
      fluorobenzyl substituent of the pyrrolidine ring and the H-bonded pseudo ring of
      the benzamide moiety are arranged in a sandwich-like manner. In the crystal,
      intermolecular hydrogen bonds link the drug molecules via the chloride anion and
      the hydrate molecule into endless helical chains around the twofold axis. The
      absolute configuration was determined by comparison of the wRtot values, 0.037
      and 0.040, calculated using all measured 2027 unique, non-zero reflections and
      assuming R and S configuration for the chiral center, respectively. Refinement of
      the structural model with an R configuration resulted in the final indices of R =
      0.031 and wR = 0.033 for 1512 reflections with I/delta(I) greater than 3.

PMID- 1387535
TI  - Oxyanion hole interactions in serine and cysteine proteases.

PMID- 1387536
TI  - Expression and molecular cloning of drought-induced genes in the wild tomato
      Lycopersicon chilense.
AB  - Protein synthesis and translatable mRNA population changes induced during water
      stress were studied in leaves of a drought-resistant wild relative of tomato,
      Lycopersicon chilense, using one- and two-dimensional polyacrylamide gel
      electrophoresis. Under our experimental conditions, water deficit did not
      significantly affect total protein synthesis capacity. However, it induced
      biphasic synthesis of a new set of proteins. These newly synthesized proteins
      resumed to control levels upon rehydration of the plants. Certain drought-induced
      proteins also accumulated in leaves subjected to heat shock (39 degrees C) or
      exogenous abscisic acid (ABA, 1 mM) treatments. A cDNA library was constructed
      using poly(A)+ RNA from leaves of plants exposed to drought stress for 4 days.
      Differential screening of the library identified three groups of clones
      corresponding to drought- and ABA-induced mRNAs. Northern blot analysis showed
      that the genes of selected clones respond differently to the different
      environmental stresses. Our data clearly demonstrate that water stress alters
      gene expression in L. chilense plants resulting in the synthesis of new proteins,
      of which several respond to high temperature stress and others to an osmotic
      effect. These responses are in part modulated by ABA.

PMID- 1387537
TI  - Mitochondrial activity and heat-shock response during morphogenesis in the
      pathogenic fungus Histoplasma capsulatum.
AB  - Changes in temperature and a variety of other stimuli coordinately induce
      transcription of a specific set of heat-shock genes in all organisms. In the
      human fungal pathogen Histoplasma capsulatum, a temperature shift from 25 to 37
      degrees C acts not only as a signal that causes transcription of heat-shock
      genes, but also triggers a morphological mycelium- to yeast-phase transition. The
      temperature-induced morphological transition may be viewed as a heat-shock
      response followed by cellular adaptation to a higher temperature. We have found
      that by inducing thermotolerance, i.e., an initial incubation at 34 degrees C,
      the thermosensitive attenuated Downs strain of H. capsulatum can be made to
      resemble those of the more temperature-tolerant G222B strain with respect to
      mitochondrial ATPase activity and electron transport efficiency at elevated
      temperatures. Furthermore, if the heat-shock response is first elicited by
      preincubation at milder temperatures or stress, transcription of heat-shock mRNA
      in mycelial cells of Downs strain that shifted to 37 degrees C proceeds at rates
      comparable to those of the virulent strains.

PMID- 1387538
TI  - Isolation and characterization of a new Ca2+/calmodulin-dependent protein kinase
      from isoproterenol-stimulated proliferating rat parotid acinar cells.
AB  - A new Ca2+/calmodulin-dependent serine kinase was isolated from rat parotid gland
      acinar cells following chronic treatment with the beta-agonist isoproterenol. A
      single-step purification was performed on a calmodulin-agarose affinity column,
      following solubilization with Triton X-100. Among various substrates tested,
      bovine galactosyltransferase was the preferred substrate of the kinase, followed
      by glycogen synthetase greater than histone greater than phosphodiesterase
      greater than phenylalanine hydroxylase greater than phosphorylase b greater than
      bovine serum albumin. In comparison, a spleen preparation of Ca2+/calmodulin
      dependent kinase did not show galactosyltransferase to be the preferred
      substrate. Thus, the enzyme would appear to be similar to the human
      galactosyltransferase-associated kinase. The kinase activity was saturable with
      100 microM Ca2+ and 2 microM calmodulin. The molecular mass determined by
      nondenaturing and sodium dodecyl sulfate polyacrylamide gel electrophoreses was
      75 kDa with a pI of 4.3. The Vmax was 3500 mumol/(min.mg protein) with a Km of
      1.6 microM for the transferase substrate. Leukotriene C and prostaglandin E2 were
      found to be specific noncompetitive inhibitors of the rat galactosyltransferase
      associated kinase.

PMID- 1387539
TI  - Rapid analysis of lambda gt11 fusion proteins without subcloning or lysogen
      induction.
AB  - Current methods of analyzing fusion proteins from lambda gt11 clones involve
      either subcloning of the insert DNA into a plasmid expression vector or
      production of lambda gt11 lysogens that are subsequently induced. Both of these
      methods can be quite time-consuming. The present communication describes a novel
      strategy for induction of the fusion protein that is both simple and rapid.
      Liquid cultures of E. coli Y1090R- infected with the lambda gt11 clone were
      induced directly to produce the fusion protein. Following the preparation of a
      crude bacterial cell lysate, fusion products were subjected to Western blot
      analysis.

PMID- 1387540
TI  - A simple method to generate single-stranded probes for run-on transcription
      assays.

PMID- 1387541
TI  - Specific distribution of an epididymal 50 kDa protein revealed by an anti-Mos
      protein monoclonal antibody.
AB  - An anti-Mos protein monoclonal antibody, 4A6, was used to investigate the
      distribution of the antigen in the epididymis, in which the c-mos gene is
      reportedly expressed. The 4A6-reactive antigen was found on the basement membrane
      and luminal surface of the epithelial cells in the caput epididymis of BALB/c
      male mice as well as in the proximal corpus epididymis, the cauda epididymis, and
      the vas deferens. The 4A6 antigen was also found on the luminal surface of the
      epithelial cells in the epididymis of male germ cell-deficient C57BL/6J-Wv/Wv
      mice. This confirmed that the 4A6 antigen does not derive entirely from the
      testicular c-Mos protein but is synthesized in the epididymis. Western blot
      analysis revealed that the molecular weight of the epididymal 4A6 antigen was 50
      kDa, which is unusually high for the c-Mos protein. With its specific
      distribution in the epididymis, the protein should play a specific role in
      functions of the epididymis.

PMID- 1387542
TI  - Autoreactive cytotoxic cells in rabbits after prolonged immunostimulation.
AB  - Rabbits immunized for 6 months with different amounts of sterile human serum
      showed weight loss and a decrease in leukocytes. The lymphocyte population
      reacting to ConA contained autoreactive cells capable of causing 51Cr release
      from labeled cells from a culture consisting of splenic and peripheral
      lymphocytic cells from the same animal.

PMID- 1387543
TI  - MTT assays allow quick and reliable measurement of the response of human tumour
      cells to photodynamic therapy.
AB  - MCF-7 and HT-29 cell lines were selected as a reliable model to examine the
      possible parameters affecting the sensitivity of tumour cells to photodynamic
      therapy (PDT) using a dye-laser at 630 nm. The chemical composition of
      haematoporphyrin derivative (HPD) was determined by high-performance liquid
      chromatography (HPLC) analysis and was in agreement with reported values. MTT
      assays were performed to assess the time-dependency of PDT and the influence of
      the output power and light fluence. The results showed a maximal cytotoxicity 48
      h after photoirradiation. The output power (1 or 2 W) did not significantly
      affect the cytotoxicity when the fluence was constant (20 J/cm2). However, an
      increase in fluence (10-40 J/cm2) led to a significant enhancement of
      cytotoxicity until maximal values were reached (30-40 J/cm2). A further increase
      in fluence (50 J/cm2) proved to induce a fall-off in cytotoxicity related to the
      intense photobleaching of HPD.

PMID- 1387545
TI  - Regression of left ventricular hypertrophy in a transplanted heart.
AB  - A woman with advanced coronary artery disease underwent heart transplantation.
      The donor heart had left ventricular hypertrophy. The electrocardiographic and
      echocardiographic evidence, of left ventricular hypertrophy regressed during
      follow up; estimated left ventricular mass decreased from 393 g to 171 g. The
      adaptation of myocardial mass and performance after transplantation is not fully
      understood. This case illustrates the potential for regression of left
      ventricular hypertrophy in response to altered loading conditions.

PMID- 1387544
TI  - Plasma concentration of atrial natriuretic peptide at admission and risk of
      cardiac death in patients with acute myocardial infarction.
AB  - OBJECTIVE: To compare the concentration of plasma atrial natriuretic peptide in
      patients with acute myocardial infarction with a healthy population and to
      determine whether a raised concentration of plasma atrial natriuretic peptide at
      admission was a predictor of mortality after acute myocardial infarction. DESIGN:
      Patients with acute myocardial infarction were divided into a group with no
      congestion (class I) and a group with congestion (class II-IV) according to their
      highest Killip classification in the first 24 hours after infarction. The
      concentration of plasma atrial natriuretic peptide was measured at admission. On
      the basis of the concentration of atrial natriuretic peptide measured in the
      healthy population, patients were separated into two groups: a group with a high
      (greater than 200 pg/ml) and a group with a low concentration of atrial
      natriuretic peptide (less than or equal to 200 pg/ml). The patients were followed
      for three years. PATIENTS: 55 patients admitted to the coronary care unit within
      12 hours of the appearance of symptoms of acute myocardial infarction were
      compared with 51 healthy individuals. MAIN OUTCOME MEASURES: Plasma atrial
      natriuretic peptide, Killip class, mortality. RESULTS: The patients had
      significantly higher concentrations of atrial natriuretic peptide than the
      healthy controls. Furthermore, patients with congestion had a significantly
      higher concentration of atrial natriuretic peptide than the uncongested group of
      patients. Total mortality was 34.5%. In the group with a low concentration of
      atrial natriuretic peptide the mortality was only 13.6%, whereas mortality was
      significantly higher (48.5%) in the group with a high concentration. CONCLUSIONS:
      The measurement of atrial natriuretic peptide separated the patients into low and
      high risk groups after acute myocardial infarction.

PMID- 1387546
TI  - Flushing and rosacea: overview and nursing interventions.
AB  - Rosacea is a dynamic facial dermatosis characterized by exacerbations and
      remissions which affects middle-aged men and women, most of whom flush easily. It
      is a conspicuous, yet treatable condition. Oral and topical antibiotics, as well
      as changes in lifestyle and elimination of aggravating factors, are necessary for
      control. Nurses facilitate compliance with the treatment regimen and optimize
      patient self-esteem.

PMID- 1387547
TI  - Surgical corrections of acne scars.
AB  - Acne, a disease of the pilosebaceous gland, may be mild or severe. Scarring,
      which occurs in both mild and severe disease, produces a variety of skin defects.
      Careful assessment of the types of scars along with knowledge about the multiple
      techniques available results in development of the most optimal plan for
      reconstruction.

PMID- 1387548
TI  - Accidental overdose of epidural bupivacaine and sufentanil.
AB  - BACKGROUND AND OBJECTIVES: A case is described of an accidental high thoracic
      epidural infusion of 337.5 mg 0.75% bupivacaine and 180 micrograms sufentanil in
      less than 30 minutes. It occurred in a post-thoracotomy patient with lung cancer.
      RESULTS: Severe hypotension and an extensive sensory and motor block developed.
      Only a mild respiratory depression was seen. The patient recovered after
      treatment without adverse sequelae.

PMID- 1387549
TI  - N-oleoyl heparin inhibits the amidolytic activity of plasmin and urokinase.
AB  - N-desulphated heparin, partially N-acylated on average with three oleoyl chains
      per molecule, inhibits the amidolytic activity of plasmin (IC50 16 nM) and
      urokinase (IC50 10mM) when assayed on N-p-tosyl-Gly-Pro-Lys-4-nitroanilide and
      benzoyl-Ala-Gly-Arg-4-nitroanilide substrates respectively. N-desulphated heparin
      is not inhibitory. This effect requires the covalent binding of oleoyl residues
      to heparin and it decreases with increasing concentration of Tris-HCl and non
      ionic detergents.

PMID- 1387550
TI  - Mutual cross-interference between glucocorticoid receptor and CREB inhibits
      transactivation in placental cells.
AB  - Transcription of the glycoprotein hormone alpha-subunit gene in placental cells
      is repressed by glucocorticoids, an effect that is mediated through the
      glucocorticoid receptor (GR). Although the DNA-binding domain of GR has been
      shown to be important, mutation of the previously identified GR-binding sites in
      the alpha-subunit promoter fails to abolish repression. Furthermore, mutant
      receptors in which the DNA-binding specificity is converted to ERE binding or in
      which the first zinc finger is substituted with that from thyroid receptor remain
      fully inhibitory, indicating that specific DNA binding to the alpha-subunit gene
      is not important for repression. Inhibition by GR is only effective when the
      alpha-subunit promoter is activated by CREB, implicating CREB as the target for
      GR-mediated repression. Reciprocally, overexpression of CREB interferes with GR
      mediated transcriptional activation of MMTV. This activity is not affected by the
      phosphorylation state of CREB. Despite the mutual cross-interference with
      activation of gene expression, GR and CREB do not appear to have a high-affinity
      protein:protein interaction in vitro. Nonetheless, GR and CREB may interact
      directly in vivo possibly through a third protein or, more likely, may sequester
      a mutually required target protein.

PMID- 1387551
TI  - The pathologic changes in long-term heart and lung transplant survivors.

PMID- 1387553
TI  - Discrimination of muscle tension in chronic pain patients and healthy controls.
AB  - The purpose of this study was to assess the perception of muscle tension in
      chronic pain patients and healthy controls. Twenty chronic back pain patients, 20
      patients who suffered from temporomandibular pain and dysfunction, and 20 healthy
      controls were instructed to produce eight different levels of muscle contraction
      in either the m. masseter or the m. erector spinae. Each level was produced three
      times; trials were presented in random order. Analyses of the accuracy and the
      sensitivity of discrimination of muscle tension levels revealed that the patients
      were less able to perceive muscle contraction levels correctly and that they
      underestimated their actual levels of muscle tension. Patients and controls did
      not differ in the extent to which they contracted muscles not involved in the
      task. Patients suffering from musculoskeletal disorders seem to display a genuine
      deficit in discrimination of muscle tension that is related to neither local
      physiological changes at the site of pain, lack of motivation, in-attention, nor
      fatigue.

PMID- 1387552
TI  - Anesthesia in pediatric heart transplantation.
AB  - Heart transplantation is a widely accepted therapy for end-stage myocardial
      failure in adults. However, few centers have experience in the treatment of
      newborns and children. The management of these children from the anesthesiologic
      viewpoint is demonstrated in our first 10 patients. Ages ranged from 5 days to 5
      years; weights ranged from 2900 gm to 16 kg. The children suffered from
      hypoplastic left heart syndrome (n = 5) or cardiomyopathy (n = 5). Eight patients
      had to receive catecholamines (dobutamine) before surgery. In neonates
      cardiopulmonary bypass (CPB) with hypothermic cardiac arrest at 18 degrees C was
      used; in the older children continuous CPB at 24 degrees to 28 degrees C was
      performed. Inotropic support during and after weaning from CPB was necessary in
      all patients who received dobutamine (range, 2 to 10 micrograms/kg/min),
      epinephrine (range, 0.03 to 1.0 microgram/kg/min), or both. The phosphodiesterase
      inhibitor enoximone (1.0 mg/kg) was administered to five patients. Prostaglandin
      E1 was given to four patients, and it was necessary to give additional tolazoline
      to two patients. Heart transplantation is a challenge for anesthesiologists
      during the prebypass period as well as during the weaning and early postbypass
      periods. More experience is necessary to optimize the anesthetic management of
      these children.

PMID- 1387554
TI  - Dog lymphocyte cultures facilitate the isolation and growth of virulent canine
      distemper virus.
AB  - Optimal conditions for the isolation and growth of virulent canine distemper
      virus (CDV) in canine thymic and peripheral blood lymphocyte cultures were
      determined. Peak virus titers were seen from 3 to 6 days postinoculation of
      lymphocytes and depended on the multiplicity of infection. Dog lymphocytes were
      at least as susceptible as canine macrophages to infection with virulent CDV.
      Virus replication in lymphocytes resulted in higher virus titers than in dog lung
      macrophages. Peripheral blood lymphocytes (PBL) from CDV-immune dogs were as
      susceptible to CDV as were PBL from susceptible dogs.

PMID- 1387555
TI  - Multiple venous thromboses and membranous obstruction of inferior vena cava in
      association with hereditary protein C deficiency: a case report.
AB  - A forty year old male presented with multiple dilated venous channels over the
      whole body involving both inferior and superior vena caval territories, along
      with features of chronic liver disease and portal hypertension. On investigation,
      he was found to have membranous obstruction of the inferior vena cava (MOIVC) as
      well as obstruction of both brachiocephalic and right subclavian veins and
      'hereditary protein C deficiency'. He was managed successfully by percutaneous
      transluminal balloon angioplasty for the inferior vena cava (IVC) obstruction and
      was doing well on follow-up.

PMID- 1387556
TI  - Behavioral effects of atrial and brain natriuretic peptides in rats.
AB  - The effects of intracerebroventricular administration of rat atrial natriuretic
      peptide (rANP-1-28) and porcine brain natriuretic peptide-32 (pBNP-32) on passive
      and active avoidance behavior and on electroconvulsive shock-induced amnesia were
      studied in rats. The dose range for both peptides was selected to lie between
      0.016 and 0.32 nmol. The two peptides were found to facilitate consolidation of
      the passive avoidance response, to delay extinction of the active avoidance
      response, and to prevent electroconvulsive shock-induced amnesia in a similar
      way. It is suggested that some modulatory functions in the central nervous system
      of the rat, so far attributed to ANP, may in fact involve a dual control by both
      ANP and BNP, and there is no difference in the biological activity of the two
      peptides as far as fear-motivated learning behavior is concerned.

PMID- 1387557
TI  - Female's DHT controls sex differences in the rat bed nucleus of the accessory
      olfactory tract.
AB  - In the present study the regulatory action of the non-aromatic androgen
      dihydrotestoterone (DHT) on the volume of the sexually dimorphic bed nucleus of
      the accessory olfactory tract (BAOT) was investigated. Postnatal treatment with
      DHT (180 micrograms day-1) between days 6 and 20 (D6-D20) induced, in gonadally
      intact male rats, a drastic reduction in the overall volume to levels typical in
      control females. Conversely, the postnatal administration of the anti-androgen
      cyproterone acetate (CA) to the females from D6-D20 produced an increment in the
      BAOT volume not dissimilar to that found in control males. These findings reveal
      that sexual organization in this vomeronasal structure is dependent on the
      presence of DHT in females during postnatal development.

PMID- 1387558
TI  - Nucleotide sequence of a cDNA encoding a beta subunit of the mitochondrial ATPase
      from rice (Oryza sativa).

PMID- 1387560
TI  - [The CT diagnosis of hemorrhages into the abdominal musculature resulting from
      therapeutic procedures on the coagulation system].
AB  - Eleven patients treated by anticoagulants or lytic therapy suffered bleeding into
      the abdominal muscles, resulting in neurological symptoms or those of an acute
      abdomen. By means of CT it was possible to demonstrate the bleeds and to clarify
      the differential diagnosis, thereby leading to correct treatment. The possibility
      of early diagnosis of haemorrhages makes CT a suitable and reliable method.

PMID- 1387559
TI  - Sorghum mitochondrial atp6: divergent amino extensions to a conserved core
      polypeptide.
AB  - Sorghum mitochondrial atp6 occurs as one copy in the line Tx398 and as two copies
      in IS1112C. In IS1112C a repeated sequence diverged within the atp6 open reading
      frames. The two open reading frames (1137 bp, atp6-1; 1002 bp, atp6-2) share an
      identical conserved region of 756 bp but are flanked 5' by divergent extensions
      of 246 (atp6-1) or 381 bp (atp6-2). Tx398 carried only atp6-2. The breakpoint of
      the repeated sequence of the conserved core region corresponds to the amino acid
      sequence Ser-Pro-Leu-Asp, which is the amino terminus of the proteolytically
      processed yeast ATP6. The 5' extensions of atp6-1 and atp6-2 were similar to
      those of rice and maize, respectively. Each open reading is transcribed, however
      nuclear background influenced transcriptional patterns of atp6-2 in IS1112C.

PMID- 1387561
TI  - Antibody responses to bacteriophage phi X174 in patients with adenosine deaminase
      deficiency.
AB  - Adenosine deaminase (ADA) deficiency and its biochemical consequences cause
      severe combined immunodeficiency (SCID). Treatment strategies, designed to
      correct the biochemical abnormalities, include transplantation of matched bone
      marrow or haploidentical bone marrow stem cells, repeated partial exchange
      transfusions with frozen irradiated human red blood cells (RBC), or weekly
      injection of polyethylene glycol-modified bovine ADA (PEG-ADA). To evaluate the
      effect of these therapeutic options, we studied in vitro T-cell function and in
      vivo antibody responses to the T-cell-dependent neoantigen, bacteriophage phi
      X174, in 10 children with ADA-deficient SCID. In untreated patients, T-cell
      function was severely depressed, and only minute amounts of antibacteriophage
      antibody were produced. Transplantation of bone marrow from a matched sibling
      (one patient) or a phenotypically matched parent (one patient) resulted in a
      stable graft, normal T-cell function, and substantial but subnormal antibody
      titers to bacteriophage, with reduced memory and impaired switch from IgM to IgG.
      Patients receiving T-cell-depleted haploidentical bone marrow stem cells had
      markedly depressed antibody responses for as long as 3 years posttransplantation,
      despite rapidly improving T-cell function that became normal in two of four
      patients. Two methods of enzyme replacement were explored. During treatment with
      human RBC transfusions, antibody responses to bacteriophage were as severely
      depressed as in untreated ADA-deficient patients. Treatment with weekly
      injections of PEG-ADA resulted in normalization of T-cell numbers in all four
      patients, normal or near-normal T-cell function in two, and mildly but variably
      improved T-cell function in the other two patients. Quantitatively and
      qualitatively normal antibody responses to bacteriophage were observed in three
      of four patients. Assessment of antibody responses to immunization with
      bacteriophage phi X174 is a useful method to monitor humoral immune function in
      treated ADA-deficient patients and can be used to estimate when intravenous
      immunoglobulin (IVIG) prophylaxis may be safely discontinued.

PMID- 1387562
TI  - Enhanced expression of interleukin-3 and granulocyte-macrophage colony
      stimulating factor receptor subunits in murine hematopoietic cells stimulated
      with hematopoietic growth factors.
AB  - AIC2A and AIC2B are closely related genes encoding components of the receptors
      for murine interleukin-3 (IL-3) (AIC2A) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) and IL-5 (AIC2B). We have studied the parallel
      regulation of expression of these genes in erythroid and myeloid progenitor cell
      lines. AIC2A and AIC2B transcription was transiently induced in these cells in
      response to a variety of hematopoietic growth factors, including erythropoietin
      (EPO), monocyte-CSF, IL-3, GM-CSF, and stem cell factor (SCF or kit ligand). Run
      on assays established that the increase occurred mainly at the transcriptional
      level. Immunoprecipitation experiments confirmed that the increase in messenger
      RNA expression resulted in augmented synthesis of both AIC2A and AIC2B proteins,
      and binding studies further showed these proteins to be functional. We observed a
      fourfold increase in low-affinity IL-3 sites in an erythroid precursor cell line
      stimulated with EPO, and a threefold increase in GM-CSF high-affinity sites in a
      myeloid cell line stimulated with IL-3. In addition, we showed that the increase
      in the IL-3 receptor chain AIC2A in the erythroid precursor cell line correlated
      with the ability of IL-3 to exert a cooperative effect with EPO in the induction
      of beta-globin in these cells.

PMID- 1387563
TI  - Neuropeptide Y (NPY) synthesis in lymphoblasts and increased plasma NPY in
      pediatric B-cell precursor leukemia.
AB  - Neuropeptide Y (NPY), a regulatory peptide in both the central and peripheral
      nervous systems, has recently been found in neuroendocrine tumors as well as in
      the bone marrow of rat and certain autoimmune mice, but not in human bone marrow.
      To investigate a possible role for NPY in the human hematopoietic system, we have
      prospectively studied NPY-like immunoreactivity in plasma (P-NPY-LI) and NPY mRNA
      in bone marrow from children with acute leukemia. Northern blot showed high
      levels of NPY mRNA in bone marrow and peripheral lymphoblasts from children with
      B-cell precursor leukemia. In situ hybridization showed NPY mRNA in malignant B
      cell precursor lymphoblasts. No NPY mRNA was detected in the bone marrow of
      children with T-cell leukemia. P-NPY-LI was higher (P less than .001) in 51
      children with leukemia (200:50 to 385 pmol/L, median:interquartile range)
      compared to 51 age-matched healthy controls (37:20 to 52 pmol/L). P-NPY-LI was
      higher (P less than .001) in those with favorable clinical risk classification.
      Elevated P-NPY-LI, compared with the upper age-adjusted reference limit, was only
      found in children with B-cell precursor leukemia (31 of 40), whereas all children
      with B-cell, T-cell, or myeloid leukemia (n = 11) had normal P-NPY-LI (P less
      than .001). During the 2- to 46-month follow-up, children with elevated P-NPY-LI
      had better (P less than .001) outcome compared to those with normal P-NPY-LI
      (79.4% v 34.6% probability for event-free survival).

PMID- 1387564
TI  - The safety and feasibility of laparoscopic cholecystectomy.
AB  - This study analyzes data from 100 consecutive patients with gallstone disease who
      underwent laparoscopic cholecystectomy (LC), a surgical technique rapidly
      emerging as the treatment of choice for this disease. LC has two major
      advantages: reduction of postoperative pain and a shortened hospital stay. LC was
      successfully completed in 88 patients, the main cause of conversion to open
      cholecystectomy being acute or chronic inflammation of the gallbladder. Analysis
      of risk factors showed that age, obesity, episodes of jaundice, pancreatitis, and
      acute or chronic cholecystitis are not absolute contraindications to LC.
      Mortality was absent and the intraoperative morbidity rate was 2%. No lesion of
      the main bile duct occurred. Seven minor post-operative complications that did
      not prolong hospital stay were also observed. These figures compare well with the
      mortality and morbidity of open cholecystectomy, and demonstrate that the
      significant benefits in terms of patient welfare and hospital costs of LC are not
      obtained at the expense of increased surgical risk.

PMID- 1387567
TI  - Multiple dopamine receptors and their implications in medicine.
AB  - Two categories of dopamine receptor were identified with classical
      pharmacological and biochemical techniques. Five different molecular species of
      dopamine receptor have been identified with molecular biological techniques. Each
      of the these five receptors can be assigned to one of the two classically
      identified dopamine receptor categories. The biology of the dopamine receptors
      can be investigated with molecular biological techniques. Recent pharmacological
      investigations show that the D1 dopamine receptor may be an important site of
      action for antiparkinsonian drugs.

PMID- 1387565
TI  - A new approach to understanding T cell development: the isolation and
      characterization of immature CD4-, CD8-, CD3- T cell cDNAs by subtraction
      cloning.
AB  - During T cell development in the mammalian thymus, immature T cells are observed
      that lack the cell surface markers CD4, CD8, and CD3. A subtracted cDNA library
      was constructed to isolate cDNAs that are specific for these immature T cells.
      Tissue-specific expression of 97 individual cDNAs were examined using different
      cell types by Northern blot analysis, and six cDNAs were analyzed by reverse
      transcriptase (RT) polymerase chain reaction (PCR) detection of RNA.
      Approximately 50% of the clones could not be detected on Northern blots, and 40%
      of the clones were expressed by at least one other cell-type including monocytes,
      mature T cells, and B cells. Eight cDNA clones appear to be specific for the CD4
      , CD8-, CD3- T cell line, used to construct the library, as determined by
      Northern blot analysis. In addition, 330 cDNA clones were subjected to partial
      automated DNA sequence determination. Database searches, with both nucleotide and
      protein translations, revealed cDNAs that exhibit interesting similarities to
      human cell-cycle gene 1, platelet-derived growth factor receptor, c-fms oncogene
      (CSF-1) receptor, and members of the immunoglobulin gene superfamily. This
      approach of employing subtraction coupled with large scale partial cDNA sequence
      determination can be useful to identify genes that may be involved in early T
      cell growth, cellular recognition or differentiation.

PMID- 1387568
TI  - Influence of age on fibre type characteristics in the middle gluteal muscle of
      Andalusian foals.
AB  - 34 Andalusian foals of both sexes were divided into three age-groups (A = mean
      age 1 month, B = 7 months, C = 14 months). Samples of the right m. gluteus medius
      were stained for m-ATPase and NADH-TR in order to determine fibre type
      composition and size as well as the relative area occupied by each type. Results
      revealed no statistically significant variation in the proportion of type I fibre
      among the three age-groups. Significant differences were recorded, however, for
      type II fibres; an increase in the proportion of IIA fibres was accompanied by a
      decrease in IIB ones, the difference being most marked between groups A and B.
      IIB high-oxidative fibres also decreased, while IIB low-oxidative ones showed no
      significant variation. All fibre types increased significantly in size; types I
      and IIA recorded a threefold increase, whereas type IIB showed least growth. The
      relative area occupied by each type increased significantly between groups A and
      B, but only IIA fibres recorded a significant increase in relative area between
      groups B and C.

PMID- 1387566
TI  - Characterization of four B-type cyclin genes of the budding yeast Saccharomyces
      cerevisiae.
AB  - The previously described CLB1 and CLB2 genes encode a closely related pair of B
      type cyclins. Here we present the sequences of another related pair of B-type
      cyclin genes, which we term CLB3 and CLB4. Although CLB1 and CLB2 mRNAs rise in
      abundance at the time of nuclear division, CLB3 and CLB4 are turned on earlier,
      rising early in S phase and declining near the end of nuclear division. When all
      possible single and multiple deletion mutants were constructed, some multiple
      mutations were lethal, whereas all single mutants were viable. All lethal
      combinations included the clb2 deletion, whereas the clb1 clb3 clb4 triple mutant
      was viable, suggesting a key role for CLB2. The inviable multiple clb mutants
      appeared to have a defect in mitosis. Conditional clb mutants arrested as large
      budded cells with a G2 DNA content but without any mitotic spindle. Electron
      microscopy showed that the spindle pole bodies had duplicated but not separated,
      and no spindle had formed. This suggests that the Clb/Cdc28 kinase may have a
      relatively direct role in spindle formation. The two groups of Clbs may have
      distinct roles in spindle formation and elongation.

PMID- 1387569
TI  - Treatment of hemodialysis fistula pseudoaneurysms with detachable balloons:
      technique and preliminary results.
AB  - Pseudoaneurysm formation is commonly encountered during the life of a dialysis
      fistula. When these become excessively large or numerous, surgical revision of
      the graft has been the only treatment option. The authors have treated seven
      patients by using percutaneous placement of a detachable balloon to occlude a
      pseudoaneurysm of an upper extremity graft. In four cases the balloon was
      directed into the pseudoaneurysm from a femoral artery approach. In three cases a
      direct puncture was made into the pseudoaneurysm for placement of the balloon.
      The patients were followed up from 1 week to 7 months. Initial technical success
      was achieved in all seven cases with no complications. Thrombosis of two grafts
      occurred during the first week after the procedure: one because of herniation of
      the balloon out of the pseudoaneurysm and one for unknown reasons. One balloon
      was inadvertently punctured and deflated during subsequent dialysis. Treatment in
      the other four cases was successful, as evidenced by no further enlargement of
      the pseudoaneurysms. Direct puncture of the pseudoaneurysm simplifies the
      procedure and probably decreases the likelihood of balloon herniation because of
      the orientation of the balloon.

PMID- 1387570
TI  - The impact of angioplasty: a perspective.

PMID- 1387571
TI  - Retrograde approach for contralateral iliac and infrainguinal percutaneous
      transluminal angioplasty: experience in 100 patients.
AB  - To assess the technical feasibility of percutaneous transluminal angioplasty
      (PTA) performed by means of a retrograde contralateral approach, 201 PTA
      procedures performed from January 1989 to August 1990 were retrospectively
      reviewed. In 100 of these cases, the retrograde femoral artery puncture employed
      for acquisition of the initial diagnostic arteriogram was also used for
      angioplasty of 173 contralateral arteries. The overall technical success rate for
      PTA via the contralateral route was 91% (157 of 173 arteries). Overall success
      for contralateral suprainguinal disease was 94% (61 of 65) and was as follows for
      infrainguinal disease: femoral, 88% (68 of 77); popliteal, 90% (18 of 20); graft
      anastomoses, 100% (five of five); and infrapopliteal, 83% (five of six). There
      were eight procedure-related complications, including one clinically
      insignificant distal atheroembolization, two sheared balloon fragments, three
      arterial thromboses, and two postprocedural amputations. There were no puncture
      related complications. PTA can be performed with a contralateral retrograde
      femoral puncture in a high percentage of patients, even when disease is well
      below the inguinal ligament.

PMID- 1387572
TI  - Superior mesenteric artery angioplasty with the TEGwire: usefulness and technical
      difficulties.
AB  - The TEGwire percutaneous transluminal angioplasty balloon on a guide wire was
      used successfully for dilation of a proximal superior mesenteric arterial
      stenosis that was not well suited to dilation by conventional angioplasty
      catheters. After the stenosis was dilated, however, the balloon deflated only
      partially due to a kink in the TEGwire as it coursed over the acute angle between
      the aorta and the superior mesenteric artery. Several unsuccessful attempts to
      correct this problem were made; finally, the partially deflated balloon and the
      guide catheter had to be withdrawn. Although the TEGwire was used within the
      guidelines and recommendations of the product, this experience supports the
      manufacturer's recommendation that the TEGwire system should not be used with
      narrow-radius vascular curves such as that formed between the superior mesenteric
      artery and the aorta.

PMID- 1387573
TI  - Visual loss and optic atrophy associated with cyproterone acetate.

PMID- 1387574
TI  - Lipoprotein(a) in cirrhosis.

PMID- 1387575
TI  - Immunodetection of annexins 1 and 2 in ciliated cells from quail oviduct.
AB  - Annexins 1 and 2 are Ca(2+)-binding proteins related to the cytoskeletal proteins
      which have been reported to bind in a calcium-dependent manner of F-actin and
      phospholipids in vitro. Proteins immunologically related to the brain 37-kDa
      annexin 1 and 36-kDa annexin 2 were characterized by immunoblotting epithelial
      ciliated cells from quail oviduct. They were detected by immunofluorescence in
      ciliated as well as glandular cells, using antisera and purified antibodies
      directed against pig brain annexins. The pattern of labeling was found in the
      apical part of both cell types, with close membrane association. However, a wider
      distribution was observed in mature ciliated cells: annexins were localized in
      the well developed cytoskeletal meshwork in which the ciliary apparatus is
      tightly anchored. After immunogold labeling, annexins 1 and 2 were located in the
      same area as spectrin 240/235 and at the connection sites of F-actin; both these
      cytoskeletals proteins were associated with the appendages of the basal body. In
      contrast, annexins were not detected in immature epithelial cells, while actin
      and spectrin were present. During ciliogenesis, the staining gradually appeared
      associated with the lateral and apical membranes. In this cellular model, the
      annexins may function during exocytosis in gland epithelial cells, where a close
      cytoskeleton-membrane association is observed; moreover, in ciliated cells, a
      relationship between cytoskeletal elements of the terminal web and annexins may
      exist.

PMID- 1387576
TI  - An intracellular study of the action of NAN-190 on neurons in the dorsal raphe
      nucleus of the rat.
AB  - Intracellular recordings have been made from neurons in the dorsal raphe (DR)
      nucleus of the rat to determine the mechanism of action of the arylpiperazine
      compound NAN-190. Application of NAN-190 (50 microM) alone most frequently caused
      a hyperpolarization accompanied by a fall in RM and reduced the response to 5-HT
      and 8-OH-DPAT. After pretreatment of the preparation with the 5-HT-uptake blocker
      citalopram (10 microM) NAN-190 exerted an excitatory effect. It is concluded that
      NAN-190 is a partial agonist in the DR nucleus.

PMID- 1387577
TI  - Glycine is required for NMDA receptor activation: electrophysiological evidence
      from intact rat hippocampus.
AB  - Fimbrial/commissural stimulation evokes a prolonged negative field potential in
      stratum radiatum of CA1 region of the rat hippocampus, in situ, upon activation
      of N-methyl-D-aspartate (NMDA) receptors. This activity can be induced by
      iontophoresis of NMDLA (50 nA) or glycine (50-100 nA) during low-frequency
      stimulation. 7-Cl-Kynurenate (10-30 nA) fully antagonized the NMDA receptor
      mediated negative wave induced not only by glycine (N = 3) but also by NMDLA (N =
      9), suggesting that activation of NMDA receptors is not possible without glycine
      binding. 7-Cl-Kynurenate also depressed the extracellular negative d.c. potential
      shifts appearing during iontophoresis of NMDLA. Stimulation with brief, high
      frequency trains evoked a negative wave of 2.1 +/- 0.2 mV and 176 +/- 4 ms (N =
      20) on the hippocampal field response following the last stimulus. Ketamine (100
      200 nA, N = 6) and MK-801 (50-200 nA, N = 7) blocked the negative wave by 74 +/-
      13 and 62 +/- 8%, respectively, while glycine (100 nA) potentiated it by 35 +/-
      2% (N = 6), indicating that it had a component mediated by NMDA receptors. 7-Cl
      Kynurenate (100 nA) antagonized this activity at a comparable rate to the NMDA
      receptor antagonists (67 +/- 8%, N = 4). A similar negative wave of 0.9 +/- 0.2
      mV and 41 +/- 3 ms (N = 12) was evoked in hippocampal slices by high-frequency
      orthodromic stimulation. Potentiation of this activity upon lowering Mg2+ in ACSF
      from 1.3 to 0.5 mM further supported that it had an NMDA-mediated
      component.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387578
TI  - Glucose and oxygen deprivation induces a Ca(2+)-mediated decrease in (Na(+)+K+)
      ATPase activity in rat brain slices.
AB  - Exposure of rat brain cortical slices to a medium lacking in glucose, oxygen or
      both glucose and oxygen, resulted in a decrease of the tissue ATP content and a
      reduction of (Na(+)+K+)-ATPase activity in membranes prepared from the slices.
      These treatments also inhibited partial reactions of (Na(+)+K+)-ATPase such as
      Na(+)-dependent phosphorylation and K(+)-stimulated phosphatase, as well as
      specific binding of [3H]ouabain in membranes prepared from the slices. Glucose
      deprivation and hypoxia decreased (Na(+)+K+)-ATPase activity in the absence of
      extracellular Ca2+, but the effects were blocked by 1,2-bis(2-amino
      phenoxy)ethane-N,N,N',N'-tetraacetic acid tetra-acetomethyl ester (BAPTA-AM), a
      chelator of intracellular Ca2+. Metabolic inhibitors mimicked the effects of
      glucose deprivation and hypoxia. The effect of glucose-free hypoxia was dependent
      on extracellular Ca2+. It was blocked by Mg2+ at high concentration, bepridil or
      amiloride, but not by voltage-sensitive Ca2+ channel antagonists and glutamate
      receptor antagonists. None of the drugs tested here, except for dithiothreitol,
      affected the inhibitory effect of glucose-free hypoxia on the enzyme activity. In
      contrast to brain (Na(+)+K+)-ATPase, the kidney enzyme was insensitive to glucose
      and oxygen deprivation and metabolic inhibitors which depleted the tissue ATP.

PMID- 1387579
TI  - Effect of atropine and PCPA on the behavioral modulation of paired-pulse response
      in the hippocampal CA1 region.
AB  - This study investigated the effect of cholinergic and serotonergic inputs on the
      paired-pulse response in hippocampal CA1 region of behaving rats. Paired-pulses
      were delivered to the Schaffer collaterals, at an interpulse interval (IPI) of 30
      ms, and field responses were recorded at the proximal CA1 apical dendritic layer.
      Previously, paired-pulse facilitation of the CA1 population spike was shown to be
      significantly larger during walking than immobility. The muscarinic cholinergic
      antagonist, atropine sulfate (50 mg/kg i.p.), strongly attenuated this paired
      pulse facilitation during walking at given amplitude of the population spike
      evoked by the first pulse. Parachlorophenylalanine (PCPA; 100 mg/kg i.p. for 3
      days), an inhibitor of serotonin synthesis, alone did not change paired-pulse
      facilitation and the combined action of PCPA and atropine resembled that of
      atropine alone. The excitatory postsynaptic potentials did not change
      significantly with behavior or after drugs. Thus, we have shown that the
      behaviorally dependent modulation of paired-pulse response in the CA1 region is
      mediated primarily by a cholinergic and not a serotonergic input.

PMID- 1387580
TI  - Induction of NMDA receptor-independent long-term potentiation (LTP) in visual
      cortex of adult rats.
AB  - The aim of this study was to examine: (1) whether long-term potentiation (LTP)
      can be induced in slices from adult rat visual cortex under conditions where
      inhibition is not antagonized, and (2) the role of N-methyl-D-aspartate (NMDA)
      receptors in its induction. The field potential elicited in layer III in response
      to stimulation of the subcortical white matter consisted of a component with peak
      latency 5-8 ms (N1) and, in most slices, a second component with peak latency 13
      19 ms (N2). N1 was generated via both kainate/alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid (AMPA) and NMDA receptor activation as revealed by bath
      application of 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5
      phosphonovalerate (APV). N2 was insensitive to APV in most of the slices and was
      probably polysynaptic since it did not follow stimulation at 0.5 Hz. Tetanic
      stimulation of the white matter in normal medium induced LTP of N1; in some
      slices N2 also potentiated. Tetanic stimulation in the presence of APV also
      induced LTP of N1 and sometimes N2. LTP of N1 induced in APV was of a larger
      magnitude, and was expressed more quickly than LTP induced in normal medium. It
      appears that the known reduction of NMDA receptor activity in adult neocortex is
      accompanied by the development of other mechanisms that maintain synaptic
      plasticity; these mechanisms seem to operate more efficiently in absence of NMDA
      receptor activation.

PMID- 1387581
TI  - Surgical management of an unusual osteomyelitis involving posterior elements in
      lumbar spine. A case report.
AB  - Improper and invasive management of low back pain may lead to an unexpected
      tragedy, vertebral osteomyelitis. A 30-year-old female patient suffering from low
      back pain after a lumbar strain called on a herbal therapist and was given a herb
      massage with some unknown medication. Unfortunately, a persistent painful ulcer
      with discharge developed over her back. She was referred to our clinic shortly
      after where x-ray showed bony destruction over the spinous process, facet, and
      lamina of L4. Fistulectomy, debridement and spinal fusion were performed. A
      satisfactory outcome was finally achieved.

PMID- 1387582
TI  - Epidemiology of low back pain in the nurses of Chang Gung Memorial Hospital.
AB  - Low back pain (LBP) caused by heavy workload or unsuitable work postures not only
      bothers a great number of persons but also presents a great challenge to the
      medical profession. This study attempts to analyze the related factors of LBP in
      nurses from the view of epidemiology, so as to offer a reference in the
      designing/redesigning of nurses' work and training programs. In this study, 3,212
      nurses were surveyed in November 1991. Only 3,159 copies of the questionnaire
      were valid for investigation; of these, 89.8% were from registered nurses, 6%
      were from nursing assistants, and 4.2% were from head nurses. Among them, 82.2%
      were still single, 17.8% were married. Their average age was 25.2 +/- 3.9 years,
      and they had worked in nursing for an average of 3.9 +/- 3.6 years. Those who
      worked in the Taipei area and the neurological department were more aware of "low
      back health care," as well as those who were head nurses and those who had
      graduated from university. Head nurses had better postures in their daily
      activities than staff nurses. Head nurses and nurses working in ICUs, and those
      who were married and had borne children or had a history of abortion had higher
      incidence of LBP. The risk factors of LBP were related to the age, height, body
      weight, duration of work, working habits and sitting posture. LBP occurs as
      frequently as 77.9% in the nursing profession. The causes of LBP were mostly
      induced by lifting heavy objects (65%) and prolonged sitting (39%). For LBP
      treatment, physical therapy was the nurses' first choice, and operation was the
      last choice.

PMID- 1387583
TI  - Brainstem glioma after radiation therapy for acute myeloblastic leukemia in a
      child with Down syndrome. Possible pathogenetic mechanisms.
AB  - A 13-year-old boy with Down syndrome (DS) had a brainstem glioma confirmed at
      autopsy, 10 years after receiving prophylactic cranial irradiation for acute
      myeloblastic leukemia. There is no clear association of brain tumors with DS;
      despite a reported link between leukemia and glioma, a causal association with
      radiation therapy is more likely.

PMID- 1387584
TI  - The role of microvascular damage in photodynamic therapy: the effect of treatment
      on vessel constriction, permeability, and leukocyte adhesion.
AB  - Intravital microscopy of the rat cremaster muscle was used to evaluate changes in
      vessel constriction, vessel permeability, and leukocyte adhesion during and after
      photodynamic therapy (PDT). Animals were given Photofrin doses of 0-25 mg/kg i.v.
      24 h before treatment. Cremaster muscles were exposed to 135 J/cm2 light at 630
      nm. Animals given 5 mg/kg Photofrin showed no vessel constriction or increase in
      vessel permeability to albumin. Doses of 10 and 25 mg/kg Photofrin caused a dose
      related constriction of arterioles which was observed within the first minutes of
      illumination at the higher drug dose. After the initial constriction, arteriole
      response to PDT was biphasic in nature, with some vessels relaxing to nearly
      control levels while others remained fully constricted. Constriction of venules
      occurred only at the highest porphyrin dose studied (25 mg/kg) and was delayed in
      comparison to arteriole constriction. Photofrin doses which produced arteriole
      constriction also caused an increase in venule permeability to albumin, which
      occurred shortly after the start of light treatment and was progressive with
      time. Leakage began at specific sites along the venule wall but became uniform
      along the entire length of the venule by 1 h after treatment. Changes in the
      adherence of polymorphonuclear leukocytes to venule endothelium were also
      observed with PDT. Photofrin doses of 25 mg/kg and 45 J/cm2 light were sufficient
      to cause polymorphonuclear leukocytes to become adherent to the vessel wall. A
      second group of animals was given indomethacin trihydrate to examine the
      involvement of cyclooxygenase products such as thromboxane in vessel response to
      PDT. Animals given 5 mg/kg indomethacin intraarterially 1 h before light
      treatment showed no constriction of arterioles or venules at all Photofrin and
      light doses studied. No increases in venule permeability to albumin were seen in
      this group of animals. This suggests that cyclooxygenase products including
      thromboxane are important in causing vessel constriction and changes in
      permeability during PDT. The initiating event which causes the release of these
      vasoactive agents remains unknown.

PMID- 1387585
TI  - Specific inhibition of interleukin 1 beta gene expression by an antisense
      oligonucleotide: obligatory role of interleukin 1 in the generation of lymphokine
      activated killer cells.
AB  - The purpose of the studies reported here is to determine whether interleukin 1
      (IL-1) plays an important role in the regulation of lymphokine-activated killer
      (LAK) cell induction. The addition of exogenous IL-1 to peripheral blood
      lymphocyte culture containing suboptimal concentrations of interleukin 2 (IL-2)
      resulted in induction of cytoplasmic pore-forming protein expression. Polymerase
      chain reaction results revealed that the mRNAs of both IL-1 alpha and IL-1 beta
      were induced within 6 h when cultured in IL-2 alone or in a combination of IL-2
      and IL-1; however, tumor necrosis factor alpha and beta mRNAs were expressed
      earlier in peripheral blood lymphocytes stimulated with the combination of IL-1
      and IL-2. Furthermore, we have examined the functional role of endogenous IL-1 in
      LAK activity. The lytic potential was significantly inhibited by an IL-1 receptor
      antagonist, which could block IL-1-mediated effects, or by specific neutralizing
      antibodies for IL-1, suggesting that the extracellular autocrine/paracrine
      pathway of IL-1 is involved in LAK activation. However, a synthetic IL-1 beta
      antisense oligonucleotide, which could specifically inhibit intracellular IL-1
      beta protein expression as detected by Western blot, was more effective in
      reducing LAK killing, but it could not suppress the cytotoxicity generated by
      exogenous IL-1 plus IL-2. These findings clearly indicate the existence of an
      intracellular IL-1 autocrine circuit. Taken together, our results strongly
      indicate that IL-1 should be considered an obligatory factor in the regulation of
      IL-2-mediated lymphocyte functions.

PMID- 1387586
TI  - Collateral sensitivity to nitrosoureas in multidrug-resistant cells selected with
      verapamil.
AB  - We have examined the effects of the nitrosoureas, streptozotocin (STZ) and 1,3
      bis(chloroethyl)-1-nitrosourea (BCNU), on a human multiple myeloma cell line,
      RPMI 8226, and its drug-resistant variants. Cell lines selected for doxorubicin
      (DOX) resistance alone displayed a STZ and BCNU cytotoxicity profile similar to
      that of the parent cell line. In contrast, two of the drug-resistant variants
      selected with DOX plus verapamil, an agent which inhibits P-glycoprotein-mediated
      multidrug resistance, displayed a collateral sensitivity to STZ and BCNU.
      Verapamil was included in the selection protocol because it has been shown to
      inhibit the P-glycoprotein-mediated multidrug resistance phenotype and is now in
      clinical trials as a chemosensitizing agent. The collateral sensitivity to these
      nitrosoureas seen in the DOX plus verapamil-selected cell lines is due to the
      functional loss of a DNA repair molecule, O6-Methylguanine DNA methyltransferase
      (MGMT). The functional loss of MGMT is secondary to the loss of MGMT gene
      expression. The loss of MGMT gene expression is not due to loss or gross
      rearrangement of the MGMT-coding region. If this selection pressure applied in
      vitro reflects the in vivo situation, then new chemotherapeutic strategies may be
      devised to exploit this phenomenon. These cell lines will serve as useful models
      for delineating mechanisms which govern MGMT expression.

PMID- 1387587
TI  - Multiple secretion of matrix serine proteinases by human gastric carcinoma cell
      lines.
AB  - Proteinase species secreted by 10 human gastric carcinoma cell lines were
      analyzed by gelatin zymography and immunoblotting. These cell lines were
      classified into the following three groups with respect to proteinase secretion:
      cell lines secreting mainly gelatinases A and/or B; those secreting multiple
      types of serine proteinases; and those scarcely secreting these enzymes. Two cell
      lines of the second group, STKM-1 and MKN28, hardly secreted metalloproteinases
      but secreted the following four types of serine proteinases: (a) two trypsin-like
      enzymes (M(r) 26,000 and 24,000 in proenzyme forms); (b) a tissue kallikrein-like
      enzyme (M(r) 150,000 in a complex form); (c) a plasmin-like enzyme (M(r) 70,000);
      and (d) a plasminogen activator (urokinase-type, M(r) 57,000, from STKM-1 and
      tissue-type, M(r) 70,000, from MKN28). The M(r) 70,000 plasmin-like enzyme was
      also detected at lower levels in the conditioned media of four other cell lines
      (MKN1, MKN45, NUGC-3, and KATO III). The M(r) 24,000 proenzyme of the trypsin
      like enzyme was purified from the serum-free conditioned medium of STKM-1. The
      proenzyme was activated by enterokinase treatment or autolytically by incubation
      at neutral pH, decreasing its apparent molecular weight from 24,000 to 23,000 on
      nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The
      activated enzyme extensively degraded fibronectin, laminin, and gelatins and to
      lesser extents type I, III, IV, and V collagens at 30 degrees C. These results
      suggest that the matrix serine proteinases may play a major role in the matrix
      degradation by some kinds of human cancer cells.

PMID- 1387588
TI  - pp59fyn mutant mice display differential signaling in thymocytes and peripheral T
      cells.
AB  - We have generated mutant mice that do not express pp59fyn, a nonreceptor protein
      tyrosine kinase related to pp60src, by homologous recombination in embryonic stem
      cells. fyn- mice did not display an overt phenotype. Because fyn is associated
      with the T cell receptor (TCR), thymocyte and T cell signaling was analyzed in
      the mutant background. Cross-linking of TCR-CD3 in thymocytes led to markedly
      reduced calcium fluxes and abrogated proliferation, whereas mature splenic T
      cells retained largely normal proliferation despite depressed calcium movements
      and IL-2 production. Similarly, proliferation induced by Thy-1 cross-linking was
      reduced in thymocytes but not in splenic T cells. fyn- thymocytes were impaired
      at a late stage of maturation and showed limited clonal deletion to the Mls-1a
      self-super-antigen but not to staphylococcal enterotoxin A. These results
      implicate fyn as a critical component in TCR signaling in thymocytes and,
      potentially, in the process that determines T cell repertoire in the adult mouse.

PMID- 1387589
TI  - Immunohistochemical studies on the distribution of cellular myosin II isoforms in
      brain and aorta.
AB  - The distribution of nonmuscle myosin isoforms in brain and aorta was studied by
      using polyclonal antibodies against two synthetic peptides selected from a region
      near the carboxyl terminus of bovine brain (peptide IIB) and human macrophage
      (peptide IIA) myosin. Immunoblots of brain homogenates and purified myosin showed
      two major bands stained by anti-peptide IIB (MIIB1 and MIIB2) and a minor band
      stained by anti-peptide IIA (MIIA2). Polyclonal anti-human platelet myosin
      antibodies did not react with MIIB isoforms. In cryosections from bovine, rat,
      and mouse brains, anti-peptide IIB stained most neuronal cells. In bovine
      cryosections, glial staining was also observed. In contrast, anti-peptide IIA and
      anti-platelet myosin antibodies primarily stained blood vessels. In bovine aorta,
      the anti-peptide antibodies recognized four bands, MIIB3, MIIB4, MIIA1, and
      MIIA2. Only MIIA2 was recognized by anti-human platelet myosin antibodies. In
      bovine aorta cryosections, anti-peptide IIB stained smooth muscle cells in tunica
      intima and tunica media but did not stain endothelial cells. Anti-peptide IIA
      stained smooth muscle cells in the tunica media, and endothelial cells of vaso
      vasorum but not of aorta. Only polyclonal anti-platelet myosin antibodies stained
      the endothelial cells of aorta tunica intima. These results indicate that
      multiple isoforms of cellular myosins exist in mammals, that these isoforms are
      expressed in a cell specific manner, and that the major myosin isoforms isolated
      from whole brain originate from neurons and, at least in bovine brain, from glia,
      but not from blood vessels.

PMID- 1387590
TI  - Cod liver oil alters platelet-arterial wall response to injury in pigs.
AB  - In 36 normolipemic pigs randomized to a 4-week feeding with regular pig chow (n =
      18, control group) or chow supplemented with cod liver oil (1 ml/kg per day) (n =
      18, treated group), treatment with cod liver oil produced a significant decrease
      in serum cholesterol, low density lipoprotein cholesterol, and triglycerides.
      Deep carotid arterial wall injury (media exposed) by balloon angioplasty was
      associated with less 111In-labeled platelet deposition (24.6 +/- 4.8 x 10(6)/cm2
      versus 62.5 +/- 17.0 x 10(6)/cm2, p less than 0.05; difference, -33.8 x
      10(6)/cm2; 95% confidence interval [CI], -1.9 x 10(6)/cm2 to -73.9 x 10(6)/cm2)
      and injury-related vasoconstriction (21.3 +/- 2.2% versus 30.9 +/- 2.9%, p less
      than 0.05; difference, -9.6%; 95% CI, -2.2% to -17.0%) in the cod liver oil
      treated group than in the control group; with mild injury (media not exposed),
      platelet deposition was low and unchanged (6.2 +/- 0.5 x 10(6)/cm2 versus 7.8 +/-
      0.7 x 10(6)/cm2; difference, -1.6 x 10(6)/cm2; 95% CI, -1.1 x 10(6)/cm2 to +4.3 x
      10(6)/cm2), but associated vasoconstriction was reduced respectively (16.3 +/-
      2.0% versus 23.0 +/- 2.2%, p less than 0.05; difference, -6.7%; 95% CI, -0.6% to 
      12.8%). When arterial blood from cod liver oil-treated pigs superfused normal
      aortic media ex vivo, platelet deposition onto the normal aortic media was lower
      than when arterial blood from control pigs superfused the normal aortic media
      (43.7 +/- 8.8 x 10(6)/cm2 versus 66.8 +/- 13.0 x 10(6)/cm2, p less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387591
TI  - Efficacy of intravenous magnesium in acute myocardial infarction in reducing
      arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial
      infarction.
AB  - BACKGROUND: To ascertain the effect of the intravenous administration of
      magnesium in acute myocardial infarction on the frequency of arrhythmias and
      mortality, a meta-analysis of randomized controlled trials was performed. METHODS
      AND RESULTS: The study included 930 patients with acute myocardial infarction
      admitted to primary referral hospitals. Administration of magnesium in acute
      myocardial infarction was associated with a 49% reduction in ventricular
      tachycardia and fibrillation. The incidence of cardiac arrest was reduced by 58%.
      The frequency of supraventricular tachycardias was also lower. Overall, there was
      a 54% reduction in mortality. CONCLUSIONS: Intravenous magnesium is a safe and
      effective method of reducing the frequency of arrhythmias and mortality in acute
      myocardial infarction.

PMID- 1387593
TI  - Erythema multiforme during danazol therapy.

PMID- 1387592
TI  - Consanguineous marriages among parents of Down patients.
AB  - In order to reveal if there is an effect on the genesis of meiotic- or early
      zygotic non-disjunctions, data related to 1598 Down syndrome patients from 1578
      families studied in five different genetic centers in Turkey are reported.
      Parental consanguinity and the inbreeding coefficient were found to be lower
      among patients of 21-trisomics than in parents without Down offspring. It was
      concluded that available information does not support the presence of a "non
      disjunction gene" in man.

PMID- 1387594
TI  - Fungal melanonychia: ungual phaeohyphomycosis caused by Wangiella dermatitidis.
AB  - A 51-year-old female Japanese patient developed black pigmentation affecting both
      big toe-nails. Direct potassium hydroxide examination of the nail tissue
      demonstrated clusters of spherical dematiaceous cells, toruloid hyphae, and
      septate hyphae. Wangiella dermatitidis was repeatedly isolated from the affected
      toe-nail lesions. This case represents the first documented case of ungual
      phaeohyphomycosis, 'fungal melanonychia,' caused by the dematiaceous fungus W.
      dermatitidis. The patient was successfully treated with a topical solution of
      bifonazole.

PMID- 1387595
TI  - Stimulation of synovial fluid mononuclear cells with the human 65-kD heat shock
      protein or with live enterobacteria leads to preferential expansion of TCR-gamma
      delta+ lymphocytes.
AB  - T lymphocyte responses to heterologous or self 65-kD heat shock protein (hsp)
      have been implicated in the pathogenesis of various forms of arthritis. To
      delineate the relationship of 65-kD hsp to different synovial fluid (SF) T cell
      subsets, we stimulated synovial fluid (SFMC) and peripheral blood mononuclear
      cells (PBMC) from patients with different inflammatory rheumatic diseases and
      from healthy controls with human or mycobacterial 65-kD hsp, tetanus toxoid (TT),
      heat-killed or live Yersinia enterocolitica. Phenotyping of the resulting T cell
      lines revealed an increase of up to 97% TCR-gamma delta+ lymphocytes in the 65-kD
      hsp-stimulated SF-derived lines. This expansion of TCR-gamma delta+ cells was
      less pronounced with cultures of PBMC. A preferential expansion of TCR-gamma
      delta+ cells was also shown after SFMC stimulation with live, but not with heat
      killed Yersinia or with TT. We conclude that a common mechanism is involved in
      the selective expansion of TCR-gamma delta+ lymphocytes upon SFMC infection with
      live Yersinia or upon contact with 65-kD hsp. Out of a panel of TCR-gamma delta+
      T lymphocyte clones (TLC) derived from a human 65-kD hsp-stimulated line, only a
      minority of TLC proliferated weakly upon restimulation with this antigen in the
      presence of autologous monocytes, whereas TCR-alpha beta+ TLC responded
      vigorously to the human 65-kD hsp and in some cases also cross-recognized the
      mycobacterial hsp homologue and/or heat-killed Yersinia. This implies that
      additional factors or cells may be present in the milieu of SFMC cultures that
      propagate the expansion of TCR-gamma delta+ cells in response to 65-kD hsp or
      live bacteria.

PMID- 1387596
TI  - T lymphocyte adhesion to fibronectin (FN): a possible mechanism for T cell
      accumulation in the rheumatoid joint.
AB  - The accumulation of T cells within the joint is responsible for the perpetuation
      of synovitis. This process is partly regulated by selective binding to
      endothelium. However, adhesion to extra-cellular matrix proteins, like FN, may
      also be important. FN binding is mediated by certain members of the VLA (beta 1
      integrin) family of proteins. To investigate the role of Tc-FN interactions in
      synovitis the binding of synovial fluid (SF) and peripheral blood (PB) T cells to
      FN-coated wells, and the expression of cell surface VLA molecules on these cells
      by double label immunofluorescence, were studied. SF T cells bound better to FN
      than PB T cells. VLA alpha 4 and VLA beta 1 but not VLA alpha 5 were up-regulated
      on SF compared with PB T cells. Anti-VLA alpha 4, VLA beta 1 and VLA alpha 5
      MoAbs inhibited the binding of SF T cells to FN. The increased binding of SF T
      cells to FN could have been related to activation and/or to their predominantly
      memory phenotype. Purified resting memory or naive T cells bound poorly to FN. In
      contrast, compared with SF T cells, concanavalin A-activated T cells showed a
      very similar level of binding to FN, comparable expression of VLA molecules and
      the same pattern of inhibition of binding to FN by MoAbs. Thus, VLA molecules may
      play an important role in the retention of T cells in the joint and since T cells
      can be activated via VLA-FN interactions, this mechanism may perpetuate chronic
      inflammation.

PMID- 1387597
TI  - Soluble CD23 levels are elevated in the serum of patients with primary Sjogren's
      syndrome and systemic lupus erythematosus.
AB  - The low affinity IgE receptor Fc epsilon RII (CD23) is important in several
      aspects of T and B cell function. In this study serum levels of soluble CD23
      (sCD23) were measured in three groups: 26 female patients with systemic lupus
      erythematosus (SLE), 21 females with primary Sjogren's syndrome (pSS) and 25
      normal healthy females. The concentration of sCD23 was determined using an
      enhanced chemiluminescent sandwich ELISA developed in this laboratory. Increased
      levels of sCD23 were observed in pSS and in SLE patients compared with controls
      (median 23.0 versus 8.6, P less than 0.0002 and 18.1 versus 8.6, P less than
      0.002 respectively). While the median level of sCD23 was found to be higher in
      pSS than in SLE the difference was not statistically significant. Patients with
      SLE and pSS on glucocorticoid treatment had significantly lower levels of sCD23
      than patients not on this treatment (median 28.9 versus 14.4, P less than 0.05).
      Amongst the control patients sCD23 was inexplicably lower in the female members
      relative to the males (median 8.5 versus 12.3, P less than 0.05). Although serum
      IgG and IgA levels were significantly elevated in pSS and SLE patients relative
      to controls there was no direct correlation between sCD23 and the serum levels of
      these immunoglobulins. We conclude that B cell hyperactivity which occurs in both
      pSS and SLE is associated with raised levels of sCD23.

PMID- 1387598
TI  - Enhanced fibrinolytic activity during the course of hemodialysis.
AB  - In order to clarify the effect of hemodialysis (HD) on the fibrinolytic system,
      fibrinolytic activity was evaluated in 27 patients undergoing regular
      hemodialysis treatment (RDT) using new parameters including plasma alpha 2
      plasmin inhibitor (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (alpha
      2 PIC), cross-linked fibrin degradation products (XL-FDP), tissue plasminogen
      activator (t-PA) activity, t-PA antigen and plasminogen activator inhibitor-1
      (PAI-1) antigen. Predialysis baseline levels of plasminogen and alpha 2PI
      activity in RDT patients were significantly lower and those of alpha 2PIC were
      significantly higher than normal control values. During a single HD session,
      alpha 2PIC exhibited a continuous, significant increase reaching about 180% of
      initial values by the end of HD. alpha 2PI activity was significantly decreased
      at the end of the HD, though there were no significant changes in plasminogen
      activity during HD. Predialysis baseline levels of XL-FDP in RDT patients were
      significantly higher than normal control values. No significant changes in XL-FDP
      were observed during HD. Both t-PA activity and t-PA antigen significantly
      increased during HD, and PAI-1 antigen significantly decreased during HD. Von
      Willebrand factor (vWF) antigen in plasma, which is regarded as reflecting a
      release reaction by vascular endothelial cells to certain stimuli, also
      significantly increased during HD. However, neither vWF antigen nor t-PA antigen
      was increased by heparin administration alone. The changes in alpha 2PI and alpha
      2PIC levels suggest that fibrinolytic activity is slightly higher in RDT patients
      and is even higher during HD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387599
TI  - Antibiotic-impregnated plaster of Paris beads. Trials with teicoplanin.
AB  - Teicoplanin-impregnated plaster of Paris beads were made and in vitro release
      properties were studied. Teicoplanin was released in an initial massive dose,
      with a rapid decline during the first three days, followed by a slowly declining
      prolonged release up to 30 days. The release tested by diffusion in gelose and
      high-performance liquid chromatography was found to be 21.4% and 28.2%,
      respectively, of the amount theoretically present in the beads. Plaster of Paris
      is a resorbable, nontoxic biomaterial that has already been used to fill dead
      spaces in bone and deliver antibiotics in the treatment of chronic osteomyelitis.
      The addition of teicoplanin, a new antistaphylococcal agent with low known
      bacterial resistance, is a promising alternative. Follow-up tests in vivo,
      simulating local conditions of the osteomyelitic bone, are necessary to prove
      efficacy.

PMID- 1387600
TI  - Uptake of hepatitis B vaccination amongst West Midlands radiologists.
AB  - A postal survey of 150 radiologists within the West Midlands Regional Health
      Authority was undertaken to obtain information about hepatitis B vaccination
      uptake and its relationship, if any, to their involvement in interventional
      radiology. Overall, 64% were vaccinated, the rate being higher amongst trainees
      (81%). No significant relationship existed between vaccination and regular
      involvement in interventional radiology. Few side effects were reported by
      radiologists (11%). Failure to seroconvert occurred in 3.5%. A telephone survey
      throughout the region suggests that many Occupational Health Departments still
      believe radiologists are not at risk from hepatitis B and therefore do not
      warrant, and are not invited for, vaccination.

PMID- 1387601
TI  - Depot-medroxyprogesterone acetate (DMPA) and risk of invasive squamous cell
      cervical cancer. The WHO Collaborative Study of Neoplasia and Steroid
      Contraceptives.
AB  - To determine whether the long-acting progestational contraceptive, depot
      medroxyprogesterone acetate (DMPA), alters risk of cervical cancer, a hospital
      based case-control study was conducted in two hospitals in Bangkok, Thailand, and
      in one hospital each in Chiang Mai, Thailand, Mexico City, Mexico, and Nairobi,
      Kenya. Information on prior use of DMPA, screening for cervical cancer, and the
      suspected risk factors for this disease was ascertained from interviews of 2,009
      women with invasive squamous cell cervical cancer and 9,583 controls. For
      selected subsets of these women, a smoking history was also elicited, blood
      specimens were collected for measurement of antibodies against herpes simplex and
      cytomegaloviruses, and information on sexual behavior was obtained from
      interviews with their husbands. The relative risk (and 95% confidence interval)
      of invasive squamous cell cervical carcinoma in women who ever used DMPA was
      estimated to be 1.11 (0.96, 1.29). No trends in risk with duration of use or
      times since initial or most recent exposure were observed. These results provide
      reassurance that prolonged use of DMPA does not enhance risk of invasive squamous
      cell cervical carcinomas, even after a potential latent period of over a decade.

PMID- 1387602
TI  - The long-term growth and development of children exposed to Depo-Provera during
      pregnancy or lactation.
AB  - Children exposed to the injectable contraceptive Depo-Provera (DMPA) during
      pregnancy (N = 1,207), and/or during breastfeeding (N = 1,215) were exposures
      during pregnancy or breastfeeding. Weights and heights were measured for all
      children, and information on signs of puberty obtained for children aged ten and
      over. Cross-sectional weights and heights by age of DMPA-exposed children were
      similar to those for controls. Children with DMPA exposure during pregnancy and
      lactation had an increased risk of suboptimal growth in height, defined as less
      than two Z scores on NCHS standards (RR = 1.4, 95% CI 1.2-1.8). However, after
      adjustment for socioeconomic factors by multiple logistic regression, there was
      no increased risk of impaired growth among the DMPA-exposed children (RR = 1.1,
      95% CI 0.8 - 1.6). With the exception of a delay in onset of reported pubic hair
      growth among DMPA-exposed girls, there were no significant effects on attainment
      of puberty. We conclude that use of DMPA during pregnancy or breastfeeding does
      not adversely affect the long-term growth and development of children.

PMID- 1387603
TI  - Fixed drug eruption in a mother and her son.
AB  - Two cases of fixed drug eruption, occurring in a mother and son, are presented.
      The eruption in the mother occurred after she ingested dimenhydrinate or
      acetylsalicylic acid and in the son after ingestion of either of the above drugs
      or with "junk" food (cheese crisps). Apart from the drugs, anxiety was found to
      be an essential factor in the manifestation of the mother's disease. A genetic
      predisposition would seem to link these cases.

PMID- 1387605
TI  - Lipoprotein(A) levels and diabetes control.

PMID- 1387604
TI  - Effects of ipratropium bromide nebulizer solution with and without preservatives
      in the treatment of acute and stable asthma.
AB  - In a recent study, it was suggested that the preservatives in ipratropium bromide
      nebulizer solution may cause a paradoxic bronchoconstrictor response in 20
      percent or more of patients with stable asthma. The frequency of this response in
      patients with acute asthma is unknown. The aim of this study was to examine the
      acute effects of the usual dose of nebulized ipratropium bromide (0.25 mg) in
      patients with either stable or acute asthma using formulations with and without
      added preservatives. Twenty-five patients with stable asthma and 25 patients with
      acute asthma were studied. Each subject was given preservative-containing
      ipratropium bromide, preservative-free ipratropium bromide, pH 7 preservative
      free ipratropium bromide, and saline solution in random order using a double
      blind crossover technique with at least 4 h between drug administrations. Very
      frequent measurements of FEV1 were made for 30 min after each drug administration
      and then 5 mg of albuterol was nebulized and the FEV1 was measured again after
      another 30 min. Changes in FEV1 were expressed as a percentage of the predicted
      FEV1. Paradoxic bronchoconstriction to ipratropium was detected in only one
      patient with acute asthma (12 percent fall in FEV1) but in none of the patients
      with stable asthma. A 6 percent fall in FEV1 change occurred with the saline
      solution in this subject suggesting that the response may have been a nonspecific
      one due to increased bronchial responsiveness. The mean response (+/- 1 SD) to
      albuterol plus either preservative-containing ipratropium, preservative-free
      ipratropium, or pH7 preservative-free ipratropium was significantly greater (p
      less than 0.05) than the response to albuterol alone both in the patients with
      acute asthma (25 +/- 12 percent, 27 +/- 15 percent, 26 +/- 15 percent, and 20 +/-
      15 percent, respectively) and stable asthma (26 +/- 7 percent, 25 +/- 8 percent,
      24 +/- 6 percent, and 22 +/- 9 percent) supporting the use of ipratropium bromide
      as an additional bronchodilator in patients with asthma who do not show a
      satisfactory response to nebulized beta-adrenergic agonist.

PMID- 1387606
TI  - [Immediate hypersensitivity to natural latex].

PMID- 1387607
TI  - Metoprolol does not reduce platelet aggregability during sympatho-adrenal
      stimulation.
AB  - The possibility that beta-adrenoceptor blockers, especially beta 1-selective
      agents might inhibit platelet function is of considerable interest, as this might
      be of pathophysiological importance in cardiovascular diseases. Platelet
      function, however, is difficult to assess and in vivo related data are scarce.
      The effect of one week of treatment with metoprolol 200 mg/day on platelet
      aggregability during mental stress (colour word conflict test; CWT) and low and
      high dose adrenaline infusions has been evaluated in a double-blind, placebo
      controlled, cross-over study in 10 healthy male volunteers. Platelet function in
      vivo was assessed using ex vivo filtragometry, and the urinary excretions of beta
      thromboglobulin (HMW beta-TG) and 11-dehydro-TxB2 (a thromboxane metabolite).
      Conventional in vitro aggregometry and the urinary levels of 2,3-dinor-6-keto
      PGF1 alpha (a prostacyclin metabolite) were also studied. During the
      interventions there was increased platelet aggregability in vivo, as
      filtragometry readings were shortened by 41 +/- 11% during high dose adrenaline
      infusion, urinary HMW beta-TG levels increased and urinary 11-dehydro-TxB2 tended
      to increase. In contrast, platelet sensitivity to ADP in vitro was reduced. The
      urinary 2,3-dinor-6-keto-PGF1 alpha levels were increased during the
      interventions. Despite the cardiovascular and biochemical signs of beta
      adrenoceptor blockade at rest and during the interventions, metoprolol failed to
      influence platelet function in vivo, as measured by ex vivo filtragometry, or
      urinary HMW beta-TG or 11-dehydro-TxB2 levels. It tended rather to enhance the
      stress response measured by ex vivo filtragometry. Platelet aggregability in
      vitro and urinary 2,3-dinor-6-keto-PGF1 alpha levels were not altered by
      metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387608
TI  - Kinetics of atrial natriuretic peptide in young and elderly subjects.
AB  - To study the influence of age on the kinetics of atrial natriuretic peptide (ANP)
      in man, human (99-126) ANP 2.0 micrograms.min-1 was infused IV for 60 min in 8
      healthy young (18 to 25 y) and 9 healthy elderly (71 to 84 y) subjects. Both
      baseline ANP values and the levels at the end of infusion were higher in the
      elderly subjects. The mean residence time of ANP in the two age groups was not
      significantly different, whereas total body clearance (CL) was markedly
      diminished in the elderly as compared to the young subjects (mean +/- SD 3.1 +/-
      1.0 l.min-1 and 6.2 +/- 4.1 l.min-1, respectively). The apparent volume of
      distribution at steady state was lower in the elderly than in the young, but the
      difference was not significant (mean +/- SD 44 +/- 19 and 103 +/- 111,
      respectively. The decrease in CL largely explained the higher ANP levels found in
      the elderly subjects. The MRT and the plasma half-life of the terminal phase did
      not differ between the two groups. In the elderly but not in the young subjects
      the calculated endogenous creatinine clearance was closely correlated with the CL
      (r = 0.90, P less than 0.001), thereby emphasizing the importance of the kidney
      in the metabolic clearance of ANP in the elderly.

PMID- 1387609
TI  - Plasma insulin during physiological and pathophysiological changes in atrial
      natriuretic factor.
AB  - Changes in plasma insulin in response to a physiological or pathophysiological
      elevation in circulating atrial natriuretic factor (ANF) have been investigated.
      Plasma insulin, glucose, immunoreactive (ir) ANF, effective renal plasma flow
      (ERPF), glomerular filtration rate (GFR), absolute and fractional excretion of
      sodium (FENa), have been measured in 14 volunteers before and during infusion of
      low doses of ANF or vehicle (V). Each subject received single-blind in a
      randomized sequence at 2 week-intervals: V alone, or ANF 4, 8 and 16 ng.kg-1.min
      1, induced over 90 min. Plasma irANF was increased 2.5- to 11-fold during the ANF
      infusion as compared to the test with the vehicle. Plasma insulin did not change
      during V administration (baseline vs V: 22 vs 21 microU.ml-1) and was unchanged
      during ANF at 4, 8 and 16 ng.kg-1.min-1 (19, 19, 21 microU.ml-1, respectively).
      Blood pressure, ERPF and GFR were not affected, and diuresis, FENa and urinary Na
      excretion were increased significantly and dose-dependently during ANF, but not V
      infusion. Compared to baseline, ANF 4, 8 and 16 ng.kg-1.min-1 increased urinary
      Na excretion by 147,241 and 446 mumol.min-1, respectively. The findings indicate
      that, in normal humans, an acute increase in irANF within or slightly above the
      physiological range, which modified natriuresis and diuresis, did not alter
      circulating plasma insulin.

PMID- 1387610
TI  - Presence of CD8 alpha-CD8 beta-positive TcR gamma/delta thymocytes in the fetal
      murine thymus and their in vitro expansion with interleukin-7.
AB  - Several groups have described that a low percentage of in vitro cultured T cell
      receptor (TcR) gamma/delta cells express CD8. Contrary to TcR alpha/beta cells,
      however, CD8 on these TcR gamma/delta cells was shown to be a CD8 alpha
      homodimer. We describe here that addition of interleukin-7 (IL-7) to a short-term
      in vitro culture of fetal day 14 thymic lobes in an organ culture system or of
      fetal day 18 fetal thymocytes in cell suspension yields CD8 beta-positive TcR
      gamma/delta cells. This is not the result of IL-7-induced expression of CD8 beta
      on previously CD8 beta-negative cells. It is due to IL-7-induced expansion of CD8
      alpha-CD8 beta-positive TcR gamma/delta cells which are shown to be present in
      the starting fetal thymocyte cell population.

PMID- 1387611
TI  - Liver of MRL/lpr mice contain interleukin-4-producing lymphocytes and accessory
      cells that support the proliferation of Th2 helper T lymphocyte clones.
AB  - Hepatic nonparenchymal cells (NPC) from mice of nonautoimmune strains support the
      proliferation of only Th1 and not Th2 helper T lymphocyte (HTL) clones. Because
      of the multiple systemic and liver-specific immune defects in the autoimmune
      MRL/lpr mouse strain, we have explored the possibility that hepatic accessory
      cells from MRL/lpr mice are capable of stimulating the proliferation of Th2 HTL.
      We report here that hepatic NPC from MRL/lpr and C3H/lpr female mice older than 8
      weeks, in contrast to hepatic NPC from MRL/++ and C3H/HeN strains, are able to
      support in vitro the proliferation of both Th1 and Th2 CD4 clones. Additionally,
      hepatic lymphocytes (HL) from MRL/lpr mice can be stimulated to produce
      interleukin (IL)-4 to a much higher degree than HL from the nonautoimmune
      strains. These results suggest that the activation of Th2 cells by hepatic NPC
      and production of IL-4 by HL may contribute to the immunologic aberrations in the
      MRL/lpr mouse strain.

PMID- 1387612
TI  - Mast cells contribute to fibrin deposition in reverse passive Arthus reaction in
      mouse skin.
AB  - The activation of the clotting system is an important process during inflammation
      to contain the injury and initiate tissue repair. In the present study, we
      investigated the effect of mast cells on fibrin deposition in reverse passive
      Arthus reaction in mast cell-deficient WBB6F1-W/Wv(W/Wv) and control WBB6F1
      (+)/+(+/+) mice, that were given 125I-labeled fibrogen intravenousty. An antibody
      dose-dependent increase in radioactivity was observed in the challenged skin
      sites. Sequential water and urea extractions characterized the radioiodinated
      fibrinogen derivatives present in the tissue. The radioactivity found in the
      various fractions of the stimulated samples from +/+ was 2-10-fold higher than
      that in specimens from W/Wv mice. The greatest difference was observed in the
      urea-insoluble pellet (cross-linked fibrin and its early degradation products).
      Reconstitution of W/Wv mice with mast cells augmented the response to levels
      similar to those in +/+ mice. Pretreatment with the antihistamine pyrilamine
      blocked the accumulation of 125I-labeled fibrinogen and its derivatives by
      approximately 70% in +/+ but not in W/Wv mice. Inhibition of leukotriene
      synthesis by A-63162 markedly decreased the accumulation of iodinated fibrinogen
      in both +/+ and W/Wv mice. The data suggest that mast cells and their vasoactive
      mediator histamine contribute to the exudation of clotting factors, which results
      in fibrin deposition and that mast cells also enhance fibrin cross-linkage.

PMID- 1387613
TI  - Distribution of interferon-gamma receptor in human tissues.
AB  - Interferon-gamma (IFN-gamma) is produced by activated T lymphocytes and plays a
      regulatory role in immune responses. The nature and location of cells that
      express the IFN-gamma receptor (R) and respond to this lymphokine are not well
      documented. The distribution of human IFN-gamma-R (HuIFN-gamma-R) was, therefore,
      investigated in situ by immunohistochemistry, using affinity-purified rabbit
      polyclonal antibodies directed against the extracellular domain of the receptor.
      In lymphoid organs, IFN-gamma-R expression is restricted to the B cell areas of
      lymph nodes, adult and fetal spleen, tonsils, appendix, and mucosa-associated
      lymphoid tissue of the small bowel. Macrophages and other reticular cells in
      lymphoid tissues and other organs are strongly positive for IFN-gamma-R, whereas
      its expression was consistently negative in the cortical and medullary
      thymocytes. Two-color flow cytofluorometric analysis of blood, lymph node,
      tonsil, spleen and thymus cells confirms that most B lymphocytes are IFN-gamma-R
      positive, whereas T lymphocytes are negative. However, after in vitro activation,
      peripheral blood T cells become IFN-gamma-R+. In non-lymphoid organs, IFN-gamma-R
      is expressed on endothelial cells of the medium- and small-size vessels. In
      epithelial tissues, high expression of IFN-gamma-R is detected on trophoblastic
      epithelium, glandular cells of stomach, ileum and colon, lung alveolar cells,
      salivary duct cells, renal tubular cells, and endometrial mucosa cells.
      Hepatocytes are weakly positive, while squamous epithelial cells are negative.
      The distribution of the HuIFN-gamma-R is discussed in view of the known functions
      of IFN-gamma.

PMID- 1387615
TI  - Restricted diversity of V gamma 9-JP rearrangements in unstimulated human
      gamma/delta T lymphocytes.
AB  - The diversity of human peripheral blood gamma/delta T cells is known to be
      limited by the preferential use of V genes coding for V gamma 9 (usually linked
      to JP) and V delta 2. We show that the diversity of these cells is further
      limited at the junctional region. First, an identical rearrangement is found in
      10%-30% of all gamma/delta T cells which contain V gamma 9-JP rearrangements.
      Second, the vast majority of V gamma 9-JP rearrangements which are different from
      this predominant sequence have, nevertheless, the same length or code for
      variable regions whose length differs by only one amino acid (+/- 1). Overall,
      30%-50% of V gamma 9-JP rearrangements have a junctional region which encodes for
      a peptide with the amino acid sequence E VX EL, in which EV is predominantly, but
      not exclusively, encoded by the germ-line V gamma 9 sequence and EL is encoded by
      JP. The X amino acid is variable, but a glutamine is over-represented. The
      diversity of the V gamma 9-JP repertoire is fairly constant in different
      individuals and at different ages, including before, during and after the post
      natal expansion of peripheral blood gamma/delta T cells.

PMID- 1387614
TI  - Limited heterogeneity of T cell receptor variable region gene usage in juvenile
      rheumatoid arthritis synovial T cells.
AB  - The aim of this study was to determine whether synovial fluid (SF) T cells in
      patients with juvenile rheumatoid arthritis (JRA) are restricted in their T cell
      receptor (TcR) gene repertoire. The quantitative polymerase chain reaction (QPCR)
      was used to compare the transcription of V beta and V alpha gene families in
      freshly isolated SF T cells, in interleukin-2 receptor-positive (IL-2R+) T cells
      and in peripheral blood (PB) T cells from 18 patients. Significantly less V beta
      families are detected in SF when compared with PB (p greater than 0.0003). The
      TcR V beta gene usage by IL-2R+ T cells was even less heterogeneous when compared
      with freshly isolated SF T cells (p greater than 0.0002). Freshly isolated SF T
      cells from the left and the right knees of four patients transcribed the same V
      beta families. Furthermore, we demonstrate that in SF the distribution of certain
      TcR V beta gene segments in CD4+ and CD8+ T cells differed from that in PB of the
      same patient. The TcR V alpha usage was studied in IL-2R+ T cells from six
      patients who had shown restriction in their SF TcR V beta gene usage. Only two to
      five TcR alpha transcripts were detected in three of these patients while a broad
      TcR V alpha usage was seen in the other three patients. Sequence analysis of the
      SF V beta 20 cDNA clones generated from the IL-2R+ T cells of two patients
      demonstrated an oligoclonal expansion. Taken together, our data could indicate an
      antigen- and/or superantigen-driven expansion of selected T cells in the synovial
      compartment.

PMID- 1387616
TI  - A new subpopulation of intestinal intraepithelial lymphocytes expressing high
      level of T cell receptor gamma delta.
AB  - The murine intestinal epithelium contains T cell receptor (TcR) gamma delta
      bearing T cells in high frequency. In the present report, we showed that TcR
      gamma delta-bearing intestinal intraepithelial lymphocytes (IEL) from C3H/He (H
      2k) mice can be divided into two subpopulations based on TcR expression level; a
      subpopulation with a remarkably high level of TcR expression and a subpopulation
      with a moderate level of TcR expression, designated as TcR gamma delta hi IEL and
      TcR gamma delta mod IEL, respectively. In flow cytometric analysis, the TcR gamma
      delta hi IEL expressed a high level of TcR (mean fluorescence channel 518) when
      compared with the TcR level of TcR gamma delta+ T cells in other lymphoid organs
      (mean fluorescence channel 88). The TcR gamma delta hi IEL were detected in IEL
      from mice of H-2k and H-2k/b haplotypes but not in H-2b and H-2d haplotypes. V
      delta 4, which was reported to be frequently expressed in IEL of H-2k mice, was
      preferentially expressed by TcR gamma delta hi IEL. These results suggested that
      the existence of the TcR gamma delta hi population is related to the high
      frequency of V delta 4 in H-2k mice.

PMID- 1387617
TI  - Heterogeneity of NMDA receptors labelled with [3H]3-((+-)-2-carboxypiperazin-4
      yl) propyl-1-phosphonic acid ([3H]CPP): receptor status in Alzheimer's disease
      brains.
AB  - The binding of [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP)
      was studied in rat and human brain synaptic membranes. Specific binding was
      saturable, reversible and inhibited by a range of compounds active at N-methyl-D
      aspartate (NMDA) receptors such as 2-amino-5-phosphonopentanoate (AP5), 2-amino-7
      phosphonoheptanoate (AP7), NMDA and cis-2,4-methanoglutamate. Binding was
      heterogeneous as evidenced by non-linear Scatchard plots and Hill coefficients
      for binding inhibitors significantly different from unity. LIGAND analysis of the
      binding data indicated the likely presence of two distinct binding components for
      CPP, one of high (Kd values approx. = 70 nM) and the other of low (Kd values
      approx. 5 microM) affinity. Possible alterations in the binding of [3H]CPP to
      either site were investigated in medial frontal and medial temporal cortex from
      Alzheimer's disease brains and compared with control tissues, carefully matched
      for age and postmortem delay. While there were considerable inter-individual
      variations in binding, no significant differences were detected either between
      brain regions in either Alzheimer or control subjects, or between Alzheimer's
      disease and control brains. These data suggest the presence of at least two
      components of [3H]CPP binding in both rat and human brain tissue. The integrity
      of neither of these components is altered in Alzheimer's disease, consistent with
      a lack of gross alterations of NMDA receptors in this disorder.

PMID- 1387619
TI  - Artifactual detection of ADP-dependent sucrose synthase in crude plant extracts.
AB  - Results presented in a previous report from this laboratory indicated the
      presence, in crude extracts from sycamore (Acer pseudoplatanus) and spinach
      (Spinacea oleracea), of a sucrose synthase (EC 2.4.1.13) showing high affinity
      for ADP as the glucose acceptor in the sucrose-cleaving reaction. In the present
      paper we report that the modified enzymatic method previously used to measure
      sucrose synthase activities leads to the detection of artifactual ADP-dependent
      sucrose synthase, which in fact arises from the combined action of invertase (EC
      3.2.1.26) and nucleoside diphosphate kinase (EC 2.7.4.6) activities. We also
      present data on the partial purification of nucleoside diphosphate kinase from
      sycamore cells.

PMID- 1387618
TI  - Methimazole treatment reduces cardiac hypertrophy and mortality without a
      concomitant reduction in blood pressure in established Goldblatt two-kidney one
      clip hypertension.
AB  - The effects of methimazole, an antithyroid drug, on blood pressure and other
      parameters were evaluated in the established phase of Goldblatt two-kidney one
      clip (G2K-1C) hypertension. Methimazole was administered via drinking water for
      five weeks, starting five weeks after hypertension had been induced. After this
      period of treatment, similarly high blood pressures were observed in methimazole
      treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state
      had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats
      showed reductions in heart rate, ventricular weight, ventricular/body weight
      ratio and mortality in comparison with rats not treated with methimazole. These
      results clearly demonstrate that hypothyroidism induced by methimazole: a) does
      not reverse G2K-1 C hypertension, but b) improves the rate of survival and c)
      reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work
      observed in Goldblatt hypothyroid rats.

PMID- 1387620
TI  - Evidence for a phosphorylation-induced conformational change in phospholamban
      cytoplasmic domain by CD analysis.
AB  - Phospholamban (PLB), an integral membrane protein of cardiac sarcoplasmic
      reticulum (SR), is described as the regulator of the Ca(2+)-ATPase pump, via its
      phosphorylation-dephosphorylation of Ser-16. Recently it has been shown that a
      direct interaction between the N-terminal hydrophilic domain of PLB and Ca(2+)
      ATPase may be one of the mechanisms of regulation. In order to show that this
      interaction could be modulated by a phosphorylation-induced conformational change
      in PLB, we ran CD studies on the synthetic peptide PLB(2-33) in its
      phosphorylated and non-phosphorylated forms, at various pHs, concentrations and
      in the absence or presence of trifluoroethanol. The results show a clear
      difference in structure of the phosphorylated and non-phosphorylated peptide.

PMID- 1387621
TI  - Particular forms of beta-N-acetylhexosaminidase in human leukaemic cells.

PMID- 1387622
TI  - Solubilization of dopamine D-1 receptors with a zwitterionic detergent DCHAPS and
      their reconstitution.
AB  - 1. Dopamine D-1 receptors of the bovine caudate nucleus were solubilized with
      different detergents. They were labelled with [3H]SCH 23390 and assayed by
      filtration through PEI-coated glass fibre filters and Sephadex G-50 columns. 2.
      DCHAPS was the best solubilizer among all detergents used and at 0.075% DCHAPS,
      10 mg/ml protein, 30 min, 4 degrees C, gave the yield of 48.7%. 3. Reconstitution
      of solubilized receptors was performed using SM-2 Bio-Beads. Phosphatidylcholine
      did not improve reconstitution suggesting that DCHAPS solubilized sufficient
      amounts of the membrane phospholipids. 4. Loss of affinity of solubilized
      receptors to [3H]SCH 23390 binding was reversible. Apparent Kd values of 0.36 +/-
      0.02, 21.3 +/- 3.2 and 0.77 +/- 0.05 nM were obtained for membrane-bound,
      solubilized and reconstituted receptors, respectively.

PMID- 1387623
TI  - The role of insulin in the intestinal absorption of glucose in the rat.
AB  - 1. Acute pre-treatment with either mannoheptulose or streptozotocin--both
      compounds acting as powerful suppressors of insulin secretion--caused a
      significant decrease on the in vivo rate of intestinal glucose absorption
      following an intragastric [U-14C]glucose administration. 2. Mannoheptulose
      treatment also lowered the rate of whole-body oxidation of the administered
      tracer. 3. Insulin had no effect on the metabolic fate of [U-14C]glucose by
      isolated enterocytes. 4. However, the rate of glucose uptake, measured by the
      oxidation of [1-14C]glucose to 14CO2 in the presence of phenazine methosulphate,
      was decreased by insulin at concentrations of 50-200 munits/ml. 5. In addition,
      the rate of transport of [U-14C]glucose by brush-border membrane vesicles was
      also inhibited by insulin at high concentrations (100-1000 munits/ml). 6. This
      indicated that insulin acts by inhibiting glucose transport in isolated in vitro
      preparations. 7. Acute pre-treatment with either mannoheptulose or streptozotocin
      caused a significant decrease in the rate of gastric emptying, measured as the
      distribution of [3H]insulin along the gastrointestinal tract, following an
      intragastric glucose load. 8. It is concluded that insulin secretion modulates
      intestinal glucose absorption in vivo by enhancing gastric emptying in spite of
      the inhibitory effects of glucose transport observed with in vitro preparations.

PMID- 1387624
TI  - Sequential expression during postnatal development of specific markers of
      junctional and free sarcoplasmic reticulum in chicken pectoralis muscle.
AB  - Skeletal muscle sarcoplasmic reticulum comprises two distinct membrane domains,
      i.e., the Ca(2+)-pump membrane, corresponding mainly to longitudinal tubules, and
      the junctional membrane of the terminal cisternae containing the ryanodine
      receptor/Ca(2+)-release channel. Additional minor proteins previously shown in
      rabbit fast-twitch skeletal muscle to fractionate selectively to each membrane
      domain comprise 160- and 53-kDa glycoproteins and 170-kDa low-density lipoprotein
      (LDL)-binding protein, respectively (Damiani and Margreth, 1991, Biochem. J. 277,
      825-832). We report evidence in chicken pectoralis, a predominantly fast muscle,
      on two closely immunologically related glycoproteins, a minor component of 130
      kDa and a major 53-kDa protein. In contrast to the seemingly highly conserved
      structure of this protein, our results show marked differences in mobilities for
      chicken 125I-LDL that were detected as a 130- to 116-kDa protein doublet after
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis, although being
      otherwise indistinguishable from rabbit 170-kDa protein in LDL-binding
      characteristics, as well as for preferential association to junctional terminal
      cisternae. Chicken Ca(2+)-ATPase, although being extensively homologous to rabbit
      Ca(2+)-ATPase, is shown to be less active and to differ slightly in
      electrophoretic properties. We have investigated the time course of expression of
      the specific protein components of longitudinal and of junctional sarcoplasmic
      reticulum in chick pectoralis muscle from late embryonic development up to 2
      months after hatching. Coincident with the posthatching increase in membrane
      density of high-affinity [3H]ryanodine-binding sites in muscle, both
      calsequestrin and the species-specific LDL-binding protein(s) are detected in
      increasing amounts, using ligand blot techniques. In contrast, the appearance and
      steady accumulation in muscle of Ca(2+)-ATPase, like the time-correlated increase
      of sarcoplasmic reticulum glycoproteins, are relatively delayed, the most
      striking changes occurring from 1 week after hatching onward. The sequential
      expression in chick developing muscle of proteins selectively associated with the
      junctional terminal cisternae and with longitudinal sarcoplasmic reticulum,
      respectively, argues for a similar morphogenetic program in avian and mammalian
      species and, to account for that, for the existence of common epigenetic
      differentiating influences on the expression of sarcoplasmic reticulum protein
      genes.

PMID- 1387625
TI  - [Effect of blood coagulation on the functional activity of transport adenosine
      triphosphatases in erythrocytes].
AB  - Membranes of red blood cells from the whole blood and the blood containing
      anticoagulant were comparatively studied in 30 donors. It was shown that their
      destabilization during blood coagulation in vitro was caused by a decrease in the
      quantity of sulfhydryl groups in red blood cell lipoprotein complexes that
      deteriorated not only structural but also functional state of erythrocytic
      membranes due to the changes in the activity of their transport ATPases.

PMID- 1387627
TI  - [Lipoprotein (a)--a risk factor for atherosclerosis].

PMID- 1387626
TI  - CLB5: a novel B cyclin from budding yeast with a role in S phase.
AB  - Budding yeast strains have three CLN genes, which have limited cyclin homology.
      At least one of the three is required for cell cycle START. Four B cyclins are
      known in yeast; two have been shown to function in mitosis. We have discovered a
      fifth B-cyclin gene, called CLB5, which when cloned on a CEN plasmid can rescue
      strains deleted for all three CLN genes. CLB5 transcript abundance peaks in G1,
      coincident with the CLN2 transcript but earlier than the CLB2 transcript. CLB5
      deletion does not cause lethality, either alone or in combination with other CLN
      or CLB deletions. However, strains deleted for CLB5 require more time to complete
      S phase, suggesting that CLB5 promotes some step in DNA synthesis. CLB5 is the
      only yeast cyclin whose deletion lengthens S phase. CLB5 may also have some role
      in promoting the G1/S transition, because cln1 cln2 strains require both CLN3 and
      CLB5 for viability on glycerol media and cln1,2,3- strains require CLB5 for
      rescue by the Drosophila melanogaster cdc2 gene. In conjunction with cln1,2,3-
      rescue by CLB5 overexpression and the coincident transcriptional regulation of
      CLB5 and CLN2, these observations are suggestive of partial functional redundancy
      between CLB5 and CLN genes.

PMID- 1387628
TI  - [Laparoscopic cholecystectomy in children].
AB  - Laparoscopic cholecystectomy is increasingly being used in adults with
      gallbladder disease. Despite the exponential increase in the number of
      laparoscopic cholecystectomies performed in adults, there are very few reports of
      its use in children. It is thought that gallstone disease is rare in childhood.
      Since the introduction of ultrasonography, it is used almost routinely for
      evaluating children with abdominal pain, and cholelithiasis is being increasingly
      recognized in children. Since the beginning of 1991 we evaluated 7 children for
      biliary colic, and on sonography gallstones were demonstrated in all of them. 1
      boy also had thalassemia and another hyperlipidemia; the other 5 developed
      symptoms of biliary colic without any history of hematological or other disease.
      5 underwent laparoscopic cholecystectomy without complication. In the other 2
      laparotomy was performed. In 1 suspected damage to the common bile duct during
      laparoscopy required direct visualization, but no damage was found. In the other,
      no gallbladder was identified on laparoscopy; laparotomy confirmed the diagnosis
      of congenital agenesis of the gallbladder with several technical modifications.
      We found laparoscopic cholecystectomy to be both safe and effective in children.
      Its advantages include shorter hospitalization, decreased postoperative
      discomfort and a much shorter interval between operation and return to normal
      activity.

PMID- 1387629
TI  - Determining suitability of placement for long-stay psychiatric inpatients.
AB  - Fifty-three long-stay patients on the back wards of a large psychiatric hospital
      in London were assessed to determine their suitability for other placements after
      the hospital was closed. The general and deviant behavior subscales of the REHAB
      Scale were used in the assessment. A wide range of scores indicated that these
      patients varied greatly in basic living skills. Associations were investigated
      between patients' scores and somatic problems, fluctuations in mental state, and
      adverse reactions to change, which affect patients' ability to live in the
      community. Of 14 patients whose scores indicated a potential for discharge, two
      had significant deviant behaviors, seven had fluctuating mental states, and two
      were known to react adversely to change. Although the REHAB Scale is useful,
      results show that placement decisions should not be based on scores alone.
      Flexible services that take into account fluctuations in patients' functioning
      are required.

PMID- 1387631
TI  - Atrial natriuretic peptide modulates baroreceptor reflex in spontaneously
      hypertensive rat.
AB  - Our previous studies have suggested that atrial natriuretic peptide in the caudal
      nucleus tractus solitarii is involved in the centrally mediated regulation of
      blood pressure in the salt-sensitive spontaneously hypertensive rat (SHR). The
      current study tested the hypothesis that endogenous atrial natriuretic peptide in
      the caudal nucleus tractus solitarii participates in baroreceptor reflex control
      of heart rate in this hypertensive model. Salt-sensitive SHR and control Wistar
      Kyoto (WKY) rats maintained on basal (1%) salt intake were studied. Arterial
      baroreceptor reflex-mediated changes in heart rate were recorded in conscious
      unrestrained rats during phenylephrine (5-40 micrograms.kg-1.min-1 infusion; 30
      minutes later, atrial natriuretic peptide (50 ng), monoclonal antibody to atrial
      natriuretic peptide (0.55 micrograms), purified mouse immunoglobulin G (0.55
      micrograms), or artificial cerebrospinal fluid vehicle (50 nl) was microinjected
      into the caudal nucleus tractus solitarii. Phenylephrine infusion was then
      repeated and mean arterial pressure and heart rate were monitored as before. The
      slope of the heart rate/mean arterial pressure relation was significantly less (p
      less than 0.05) in the salt-sensitive SHR than in the WKY control, indicating
      that baroreceptor reflex control of heart rate was blunted in this hypertensive
      model. Microinjection of atrial natriuretic peptide into the caudal nucleus
      tractus solitarii further blunted (p less than 0.05) baroreceptor reflex control
      of heart rate in salt-sensitive SHR but not in WKY rats. In contrast,
      microinjection of the monoclonal antibody enhanced the sensitivity of
      baroreceptor reflex control of heart rate in salt-sensitive SHR but not in WKY
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387630
TI  - Prognostic significance of exercise blood pressure and heart rate in middle-aged
      men.
AB  - Systolic blood pressure and heart rate measured at rest and during a standardized
      exercise test were analyzed in the cohort of middle-aged male employees followed
      up an average of 17 years in the Paris Prospective Study I. The population sample
      selected for the analysis included 4,907 men who completed at least 5 minutes of
      bicycle ergometry, who had no heart disease at entry, and whose resting blood
      pressure was less than or equal to 180/105 mm Hg. Exercise-induced increase in
      systolic blood pressure was positively correlated with resting systolic blood
      pressure (r = 0.104, p less than 0.0001), whereas the correlation of exercise
      induced heart rate increase with resting heart rate was negative (r = -0.169, p
      less than 0.001). Using Cox regression analysis with the inclusion of resting
      systolic blood pressure and heart rate; exercise-induced elevations of systolic
      blood pressure and heart rate; and controlling for age, smoking, total
      cholesterol, body mass index, electrical left ventricular hypertrophy, and sports
      activities, cardiovascular mortality was found to be associated with the systolic
      blood pressure increase (p less than 0.05), whereas no association with resting
      systolic blood pressure was found. Total mortality was predicted by resting
      systolic blood pressure and its elevation (p less than 0.01 for both) and by
      resting heart rate (p less than 0.0001). The heart rate increase did not
      contribute to death prediction. In conclusion, the magnitude of the exercise
      induced increase of systolic blood pressure, but not of heart rate, may represent
      a risk factor for death from cardiovascular as well as noncardiovascular causes,
      independently of resting blood pressure and heart rate.

PMID- 1387632
TI  - Some mechanical/hydrodynamical problems of contemporary vascular grafts.
AB  - In view of the importance of properly matching vascular grafts and replaced
      arteries, we measured some mechanical properties of a set of eleven vascular
      grafts. The deformation response of inflated grafts for a set of Czechoslovak
      made warp and weft knitted grafts was also measured on a special experimental
      device. A simple two-parameter model describing the stress-strain behavior of the
      grafts is given. Proper pre-elongation of the graft during implantation is
      important. From the hydrodynamic point of view it is essential to optimize the
      size and shape of the crimping, especially for small-diameter grafts. Our
      experiments indicate that the warp knitted grafts are more distensible than the
      weft knitted ones, but they are all more rigid than the replaced arteries.

PMID- 1387633
TI  - Duplex imaging of lower limb arterial bypass grafts.
AB  - A non-invasive programme of post-operative surveillance and intervention where
      necessary is essential to optimise results with arterial reconstruction. We
      report our experience with duplex ultrasonography in the follow-up lower limb
      arterial bypass grafts. One hundred and three duplex studies were performed in 58
      patients with 59 lower limb arterial bypass grafts. Grafts were visualised
      throughout their length and haemodynamic characteristics including peak systolic
      velocity (PSV) were measured. Angiography was performed on the basis of any
      significant anatomical or haemodynamic abnormality on duplex. All grafts were
      visualised throughout their length with ease. Satisfactory visualisation of 86%
      of anastomoses was achieved. PSV was found to be the most easily reproducible
      haemodynamic index and the best indicator of graft function. PSV had a median
      value of 79 cm/sec and a range of 51-117 cm/sec in normal grafts compared to 26
      cm/sec (range 19-42 cm/sec) in grafts with stenosis. Twelve pre-occlusive lesions
      which were not evident clinically, 5 within and 7 outside the graft, have been
      detected. Eight have been treated by transluminal angioplasty. Two grafts with
      stenosis and PSVs of less than 25 cm/sec had occluded by the time angiography was
      performed 2 weeks later. Duplex is an excellent, non-invasive, and repeatable
      method of screening of grafts at risk of failure, allowing earlier intervention
      with improved secondary patency.

PMID- 1387635
TI  - ES-242-2, -3, -4, -5, -6, -7, and -8, novel bioxanthracenes produced by
      Verticillium sp., which act on the N-methyl-D-aspartate receptor.
AB  - Verticillium sp. SPC-15898 was found to produce novel metabolites, designated ES
      242-2-(-)8, which were structurally related to ES-242-1. These compounds were
      isolated from the culture broth and the physico-chemical and biochemical
      properties were examined. ES-242-2-(-)8 inhibited [3H]thienyl cyclohexypiperidine
      ([3H]TCP) binding to rat crude synaptic membranes (CSM) with IC50 values of
      0.116, 2.9, ca. 2.9, 25.3, 1.0, 59, 24, and 13 microM, respectively. None of
      these compounds showed inhibitory effects against the binding of [3H]kainate to
      its receptor, which is another subtype of the excitatory amino acid receptor.

PMID- 1387634
TI  - Efficacy and specificity of a monoclonal antibody-drug conjugate in chemotherapy
      by intratumoral injection.
AB  - The murine monoclonal antibody (Mab) A7 conjugated to neocarzinostatin (A7-NCS)
      was injected intratumorally (IT) into tumor bearing nude mice. Its
      pharmacokinetics and tumoricidal effects were compared in the high, moderate and
      low antigen expressing xenograft for SW1116, WiDr and KB tumor-bearing nude mice,
      respectively. When injected IT into nude mice, [125I]A7-NCS was retained in the
      tumors according to the degree of antigen expression; it was also disseminated
      into the blood inverse proportion to the antigen expression. Addition of an
      excess amount of Mab A7 reduced [125I]-A7-NCS accumulation in SW1116 xenograft
      and elevated the [125I]A7-NCS concentration in the circulation. Complete tumor
      reduction was found in all 5 mice with SW1116 tumor, and 2 of 5 mice with WiDr
      tumor. However, only incomplete tumor suppression was observed in mice with the
      KB tumor. The significant tumor reduction in SW1116 bearing nude mice was
      attenuated when excess of Mab A7 was simultaneously administered with A7-NCS.
      These findings indicate that A7-NCS was localized in the target tumors and
      exerted its tumoricidal effects depending on the degree of antigen-antibody
      interaction when administered IT. Thus, A7-NCS can be used successfully in vivo
      for local therapy, auguring new and promising applications for local cancer
      therapy.

PMID- 1387636
TI  - New directions in antidepressant therapy: a review of sertraline, a unique
      serotonin reuptake inhibitor.

PMID- 1387637
TI  - Solubilization and molecular size determination of the P2x purinoceptor from rat
      vas deferens.
AB  - Membranes of the rat vas deferens were shown to contain a high density of binding
      sites for [3H] alpha, beta-methylene ATP ([3H] alpha, beta-MeATP), a ligand
      selective for the P2X purinoceptor. Analysis demonstrated two classes, of high
      affinity (Kd = 1.8 nM, Bmax (maximum density) = 9.3 pmol/mg of protein) and of
      low affinity (Kd = 34 nM, Bmax = 29 pmol/mg of protein). The high affinity [3H]
      alpha, beta-MeATP binding sites were successfully solubilized with 2% digitonin:
      the Kd was then 1.6 nM. Both the association and dissociation of the receptor
      ligand complex were rapid (half-time for association = 6.5 min). The rank order
      of potency of purinergic ligands in displacing [3H] alpha, beta-MeATP binding
      from the solubilized preparation was in accord with the pharmacological criteria
      for P2X purinoceptors. The receptor-detergent complex was separated by sucrose
      gradient ultracentrifugation from the ATPase enzymes also present in the
      preparation. The sedimentation coefficient of the receptor-detergent complex was
      12.1 S. It was shown that [3H] alpha, beta-MeATP can function as a photoaffinity
      labeling reagent upon exposure to ultraviolet light; in the rat vas deferens
      membranes, it thus became cross-linked in a specific manner to a polypeptide of
      apparent molecular mass = 62,000 daltons, proposed to be the ligand-binding
      subunit of the functional P2X purinoceptor.

PMID- 1387639
TI  - Active site of (A)BC excinuclease. I. Evidence for 5' incision by UvrC through a
      catalytic site involving Asp399, Asp438, Asp466, and His538 residues.
AB  - (A)BC excinuclease of Escherichia coli removes damaged nucleotides from DNA by
      hydrolyzing the 8th phosphodiester bond 5' and the 15th phosphodiester bond 3' to
      the modified base. The activity results from the ordered action of UvrA, UvrB,
      and UvrC proteins. The role of UvrA is to help assemble the UvrB.DNA complex, and
      it is not involved in the actual incision reactions which are carried out by UvrB
      and UvrC. To investigate the role of UvrC in the nuclease activity a subset of
      His, Asp, and Glu residues in the C-terminal half of the protein were mutagenized
      in vitro. The effect of these mutations on UV resistance in vivo and incision
      activity in vitro were investigated. Mutations, H538F, D399A, D438A, and D466A
      conferred extreme UV sensitivity. Enzyme reconstituted with these mutant proteins
      carried out normal 3' incision but was completely defective in 5' incision
      activity. Our data suggest that UvrC makes the 5' incision by employing a
      mechanism whereby the three carboxylates acting in concert with H538 and a Mg2+
      ion facilitate nucleophilic attack by an active site water molecule.

PMID- 1387638
TI  - Thapsigargin activates a calcium influx pathway in the unfertilized mouse egg and
      suppresses repetitive calcium transients in the fertilized egg.
AB  - At fertilization, the sperm initiates development of the mouse egg by inducing a
      large transient increase in the intracellular Ca2+ concentration ([Ca2+]i), which
      is followed by repetitive transient increases in [Ca2+]i. To determine how the
      repetitive Ca2+ transients are produced, thapsigargin, an inhibitor of the
      endoplasmic reticulum Ca-ATPase, was used to deplete intracellular Ca2+ stores
      within the egg. In the unfertilized egg, thapsigargin (1-50 microM) caused a
      slowly rising and falling transient increase in [Ca2+]i with or without
      extracellular Ca2+. An influx pathway for Ca2+ is activated by thapsigargin,
      since an immediate increase in [Ca2+]i occurred when Ca2+ was added to eggs after
      thapsigargin treatment in a Ca2+, Mg(2+)-free medium. This suggests that Ca2+
      entry in the mouse egg may be coupled to the emptying of an intracellular store.
      The magnitude of the first Ca2+ transient at fertilization was reduced by as much
      as 84% in eggs pretreated with thapsigargin. Reduction of extracellular Ca2+, by
      addition of a Ca2+ chelator, suppressed the repetitive Ca2+ transients following
      fertilization. The Ca2+ transients also require filling of an intracellular
      store; they were suppressed when thapsigargin was added before or after
      fertilization. These results support the hypothesis that the first sperm-induced
      Ca2+ transient at fertilization depletes an intracellular Ca2+ store, triggering
      an increase in plasma membrane Ca2+ permeability, and that the enhanced Ca2+
      influx causes repetitive Ca2+ transients due to the periodic filling and emptying
      of an intracellular Ca2+ store.

PMID- 1387641
TI  - Vampire bat salivary plasminogen activator exhibits a strict and fastidious
      requirement for polymeric fibrin as its cofactor, unlike human tissue-type
      plasminogen activator. A kinetic analysis.
AB  - The vampire bat salivary plasminogen activator (BatPA) is virtually inactive
      toward Glu-plasminogen in the absence of a fibrin-like cofactor, unlike human
      tissue-type plasminogen activator (tPA) (the kcat/Km values were 4 and 470 M-1 s
      1, respectively). In the presence of fibrin II, tPA and BatPA activated Glu
      plasminogen with comparable catalytic efficiencies (158,000 and 174,000 M-1 s-1,
      respectively). BatPA's cofactor requirement was partially satisfied by polymeric
      fibrin I (54,000 M-1 s-1), but monomeric fibrin I was virtually ineffective (970
      M-1 s-1). By comparison, a variety of monomeric and polymeric fibrin-like species
      markedly enhanced tPA-mediated activation of Glu-plasminogen. Fragment X polymer
      was 2-fold better but 9-fold worse as cofactor for tPA and BatPA, respectively,
      relative to fibrin II. Fibrinogen, devoid of plasminogen, was a 10-fold better
      cofactor for tPA than fibrinogen rigorously depleted of plasminogen, Factor XIII,
      and fibronectin; the enhanced stimulatory effect of the less-purified fibrinogen
      was apparently due to the presence of Factor XIII. By contrast, the two
      fibrinogen preparations were equally poor cofactors of BatPA-mediated activation
      of Glu-plasminogen. BatPA possessed only 23 and 4% of the catalytic efficiencies
      of tPA and two-chain tPA, respectively, in hydrolyzing the chromogenic substrate
      Spectrozyme tPA. However in the presence of fibrin II, BatPA and tPA exhibited
      similar kcat/Km values for the hydrolysis of Spectrozyme tPA. Our data revealed
      that BatPA, unlike tPA, displayed a strict and fastidious requirement for
      polymeric fibrin I or II. Consequently, BatPA may preferentially promote plasmin
      generation during a narrow temporal window of fibrin formation and dissolution.

PMID- 1387640
TI  - Active site of (A)BC excinuclease. II. Binding, bending, and catalysis mutants of
      UvrB reveal a direct role in 3' and an indirect role in 5' incision.
AB  - UvrB plays a central role in (A)BC excinuclease. To study its role in the
      incision reactions, conserved His and Asp residues in this subunit were
      mutagenized. All His and the majority of Asp mutants behaved like wild-type
      protein in vivo and in vitro. However, three mutants, D337A, D478A, and D510A,
      either completely or partially abolished UvrB activity. All three mutant proteins
      associate with UvrA normally but D337A and D510A were unable to bind to DNA
      specifically. The UvrB-D478A mutant bound to DNA specifically but failed to
      denature and kink the DNA. However, UvrB-D478A was efficiently loaded onto DNA
      preincised at the 3' site and promoted near-normal incision by UvrC at the 5'
      site. We propose that D478 is involved in bending DNA and catalysis of the 3'
      incision and that the 3' incision precedes the 5' incision. UvrB which is missing
      the carboxyl-terminal 43 amino acids binds to, and kinks DNA but is unable to
      make the 3' incision suggesting that it is missing a residue involved in
      catalysis. This residue was identified to be E639 by site-specific mutagenesis.

PMID- 1387643
TI  - Clustering of lipid-bound annexin V may explain its anticoagulant effect.
AB  - In 1985 we isolated a new vascular anticoagulant protein VAC alpha, now called
      annexin V, with a high binding affinity (Kd less than 10(-10) M) for
      phospholipids. Its anticoagulant effect was attributed to displacement of
      coagulation factors from the phospholipid membrane. The present study
      demonstrates that the inhibition of prothrombinase activity by annexin V strongly
      depends on the curvature of the membrane surface and on the calcium
      concentration. Half-maximal inhibition of prothrombinase on and binding of
      annexin V to small vesicles, composed of 20% phosphatidylserine and 80%
      phosphatidylcholine, requires 2-3 mM calcium. With large vesicles and planar
      bilayers considerably less calcium is required for inhibition of prothrombinase
      and for lipid binding. Half-maximal binding of annexin V to large vesicles and to
      planar bilayers occurs at 0.7 and 0.2 mM calcium, respectively. This seemingly
      confirms the displacement model. The displacement of coagulation factors,
      however, proved to be incomplete, with residual surface concentrations of factors
      Xa, Va, and prothrombin sufficient for effective production of thrombin.
      Cryoelectron microscopy revealed that annexin V binding to large vesicles caused
      planar facets, indicating the formation of large sheets of clustered annexin V.
      Apparently, the formation of these two-dimensional arrays is promoted by calcium
      and hampered by high surface curvature. It is speculated that the complete
      inhibition (greater than 99%) of prothrombinase activity by annexin V is caused
      by the reduced lateral mobility of prothrombin and factor Xa in rigid sheets of
      annexin V covering the membrane.

PMID- 1387642
TI  - Interactions of a laminin-binding peptide from a 33-kDa protein related to the 67
      kDa laminin receptor with laminin and melanoma cells are heparin-dependent.
AB  - A laminin-binding peptide (peptide G), predicted from the cDNA sequence for a 33
      kDa protein related to the 67-kDa laminin receptor, specifically inhibits binding
      of laminin to heparin and sulfatide. Since the peptide binds directly to heparin
      and inhibits interaction of another heparin-binding protein with the same
      sulfated ligands, this inhibition is due to direct competition for binding to
      sulfated glycoconjugates rather than an indirect effect of interaction with the
      binding site on laminin for the 67-kDa receptor. Direct binding of laminin to the
      peptide is also inhibited by heparin. This interaction may result from
      contamination of the laminin with heparan sulfate, as binding is enhanced by the
      addition of substoichiometric amounts of heparin but inhibited by excess heparin
      and two heparin-binding proteins. Furthermore, laminin binds more avidly to a
      heparin-binding peptide derived from thrombospondin than to the putative receptor
      peptide. Adhesion of A2058 melanoma cells on immobilized peptide G is also
      heparin-dependent, whereas adhesion of the cells on laminin is not. Antibodies to
      the beta 1-integrin chain or laminin block adhesion of the melanoma cells to
      laminin but not to peptide G. Thus, the reported inhibition of melanoma cell
      adhesion to endothelial cells by peptide G may result from inhibition of binding
      of laminin or other proteins to sulfated glycoconjugate receptors rather than
      from specific inhibition of laminin binding to the 67-kDa receptor.

PMID- 1387644
TI  - An active covalently linked dimer of human interferon-gamma. Subunit orientation
      in the native protein.
AB  - We have constructed and expressed a covalently linked head to tail dimer of human
      interferon-gamma (IFN-gamma) in which two monomers are joined head to tail via a
      rigid peptide hinge using genetic engineering techniques. The hinge was derived
      from the human immunoglobin IgA1 sequence (Hallewell, R.A., Laria, I., Tabrizi,
      A., Carlin, G., Getzoff, E.D., Tainer, J.A., Cousens, L.S., and Mullenbach, G.T.
      (1989) J. Biol. Chem. 264, 5260-5268). Analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis shows that the polypeptide produced by this
      construction migrates as a 30,000 polypeptide species. The protein elutes as a
      single species by molecular sieve chromatography under native conditions. The
      covalently linked dimer exhibits one-half the antiviral activity of native
      dimeric IFN-gamma; receptor binding assays show the covalently linked dimer binds
      to the IFN-gamma receptor with one-half the avidity of native IFN-gamma. This
      difference is not due to conformational differences between the two molecules, as
      the aromatic region of the NMR spectrum of the purified covalently linked dimer
      is identical with that of the wild type protein. From these data, we suggest that
      human IFN-gamma associates in a head to tail dimer in its active configuration.
      Regions of IFN-gamma are contiguous with the amino and carboxyl termini and are
      obscured by the hinge peptide in the covalently linked dimer. Our studies
      demonstrate that these regions may be important for receptor-ligand interaction.

PMID- 1387645
TI  - Human lysosomal protective protein. Glycosylation, intracellular transport, and
      association with beta-galactosidase in the endoplasmic reticulum.
AB  - In lysosomes beta-galactosidase and neuraminidase acquire a stable and active
      conformation through their association with the protective protein. The latter is
      homologous to serine carboxypeptidases and has cathepsin A-like activity which is
      distinct from its protective function towards the two glycosidases. To define
      signals in the human protective protein important for its intracellular
      transport, and to determine the site of its association with beta-galactosidase,
      we have generated a set of mutated protective protein cDNAs carrying targeted
      base substitutions. These mutants were either singly transfected into COS-1 cells
      or cotransfected together with wild type human beta-galactosidase. We show that
      all point mutations cause either a complete or partial retention of the
      protective protein precursor in the endoplasmic reticulum. This abnormal
      accumulation leads to degradation of the mutant proteins probably in this
      compartment. Only the oligosaccharide chain on the 32-kDa subunit acquires the
      mannose 6-phosphate recognition marker, the one on the 20-kDa subunit seems to be
      merely essential for the stability of the mature protein. In cotransfection
      experiments, wild type beta-galactosidase and protective protein appear to
      assemble already as precursors, soon after synthesis, in the endoplasmic
      reticulum. Mutated protective protein precursors that are retained in the
      endoplasmic reticulum or pre-Golgi complex interact with and withhold normal beta
      galactosidase molecules in the same compartments, thereby preventing their normal
      routing.

PMID- 1387646
TI  - Experimental determination of velocity profiles and wall shear rate along the
      rabbit aortoiliac bifurcation: relationship to vessel wall low-density
      lipoprotein (LDL) metabolism.
AB  - We have determined the velocity profiles and wall shear rates along the New
      Zealand White (NZW) rabbit aortoiliac bifurcation. A pulsatile perfusion
      apparatus was used to impose physiologic pressure and flow waveforms on nine
      freshly excised NZW bifurcation segments. Pulsed Doppler velocimetry (PDV) was
      utilized to construct velocity profiles at five measurement sites: within the
      infrarenal aorta; immediately distal to the apex of the bifurcation; and, more
      distally along the iliac arteries. Wall shear rate was derived from a numerical
      differentiation of the experimental velocity profiles. The results of this study
      indicate that the average shear rate was lower along the lateral (approximately
      40 s-1) vs medial (approximately 240 s-1) wall of the proximal iliac branch. The
      degree of flow reversal along the proximal lateral walls (20 +/- 2%) exceeded
      that along the proximal flow divider wall (1 +/- 1%). Flow at the distal iliac
      measurement sites and within the infrarenal aorta was approximately symmetric.
      These findings complement our companion in vivo study [Berceli et al.,
      Arteriosclerosis 10, 688-694 (1990)] wherein we determined the rates of low
      density lipoprotein (LDL) incorporation and catabolism along this symmetrically
      bifurcating conduit. Taken together, these studies provide original information
      regarding the effects of hemodynamics on one presumed atherogenic risk factor,
      namely, LDL metabolism.

PMID- 1387647
TI  - Arterial, portal or combined arterio-portal regional chemotherapy in experimental
      liver tumours?
AB  - The most appropriate route for regional administration of chemotherapeutic drugs
      to liver tumours was studied in a standardized rodent model: cells of Novikoff
      hepatoma were transplanted into the central liver lobe of Sprague-Dawley rats.
      From day 5 to day 12 after transplantation, the liver was continuously perfused
      with 420 mg/kg 5'-fluoro-2-deoxyuridine by subcutaneous osmotic micropumps via
      the hepatic artery (n = 20), the portal vein (n = 20) or both vessels together (n
      = 12). The tumour multiplication factor (TMF) and the vascularization of the
      tumour were evaluated. Arterial and combined infusion led to a highly significant
      reduction in TMF, but combined infusion was not more effective than arterial
      alone. Portal infusion had no significant effect. There was no correlation
      between vascularization and tumour response in arterial infusion, but a strong
      correlation in portal infusion. Thus chemotherapy via the portal route may be
      effective in selected tumours with considerable portal vascularisation.

PMID- 1387649
TI  - High-performance liquid chromatographic determination of usnic acid in plasma.
AB  - A high-performance liquid chromatographic method for the determination of usnic
      acid in human plasma using diclofenac sodium as internal standard is described.
      Plasma proteins were precipitated with methanol. A 250 mm x 4 mm I.D. Nucleosil.
      C18 (5 microns) column with a mobile phase consisting of methanol-phosphate
      buffer (pH 7.4) (70:30, v/v) was used. Chromatography was performed at ambient
      temperature with flow-rate of 1 ml min-1 and ultraviolet detection at 280 nm.
      Each analysis required no longer than 7 min. Quantification was achieved by
      measurement of the peak-height ratio and the absolute recovery varied from 93.8
      to 97.3%. The limit of quantitation of usnic acid in plasma was 0.25 micrograms
      ml-1. The intra-day relative standard deviation (R.S.D.) ranged from 1.24 to
      4.53% and the inter-day R.S.D. from 2.23 to 8.25% at three different
      concentrations. The method was applied to the determination of plasma levels of
      usnic acid after intravenous and oral administration to study its disposition in
      a healthy male rabbit.

PMID- 1387648
TI  - Frequent spontaneous sister chromatid exchange in hepatocytes of transgenic mice
      harboring the SV40-T antigen gene.
AB  - In order to shed light on the causal mechanisms of hepatocarcinogenesis in the
      transgenic mouse into which the albumin-promotor-regulated SV40-T antigen gene
      has been introduced (T+ mouse), and especially on the frequent chromosomal
      aberrations seen in cultured hepatocytes and hepatocellular neoplasms derived
      from such animals, the frequency of sister chromatid exchange (SCE) and karyotype
      abnormalities were investigated in a hepatocyte primary culture system. Cells
      were obtained through collagenase perfusion from T+ mice at 16-18 days of age,
      when no morphological changes are apparent, and from nontransgenic littermates,
      and cultured in the presence of bromodeoxyuridine. SCE was seen in transgenic
      hepatocytes twice as frequently as in their normal counterparts. No karyotype
      abnormalities in terms of numerical change or gross aberration were detected at
      this phase. The results thus suggest mutagenic properties for the T antigen,
      which may play an important role in hepatocarcinogenesis in this transgenic
      mouse.

PMID- 1387650
TI  - Quantification of 5-fluoro-2'-deoxyuridine in plasma by gas chromatography and
      negative-ion chemical ionization mass spectrometry.
AB  - A sensitive and specific method using gas chromatography and negative-ion
      chemical ionization mass spectrometry is described for the determination of 5
      fluoro-2'-deoxyuridine (FdUrd) in plasma. The method is based on the formation of
      the pentafluoropropionyl derivative of FdUrd and of its stable isotope as
      internal standard after sample clean-up by solid-phase extraction and
      purification by high-performance liquid chromatography. Quantification in plasma
      was possible down to 300 pg/ml. The method was applied to the analysis of plasma
      levels of FdUrd in mice and dogs.

PMID- 1387651
TI  - Affinity purification of proteins using expanded beds.
AB  - The use of expanded beds of affinity adsorbents for the purification of proteins
      from feedstocks containing whole or broken cells is described. It is demonstrated
      that such feedstocks can be applied to the bed without prior removal of
      particulate material by centrifugation or filtration thus showing considerable
      potential for this approach in simplifying downstream processing flow-sheets. A
      stable, expanded bed can be obtained using simple equipment adapted from that
      used for conventional packed bed adsorption and chromatography processes.
      Circulation and mixing of the adsorbent particles is minimal and liquid flow
      through the expanded bed shows characteristics similar to those of plug flow.
      Frontal analysis performed with the highly selective affinity system involving
      the adsorption of human polyclonal immunoglobulin G onto Protein A Sepharose Fast
      Flow indicate that the adsorption performance of the expanded bed is similar to
      that achieved when the same amount of adsorbent is used in a packed configuration
      at the same volumetric flow-rate. The adsorption performance of the expanded bed
      was not diminished when adsorption was carried out in the presence of intact
      yeast cells. Batch adsorption experiments also indicated that the adsorption
      characteristics of the affinity system were not greatly altered in the presence
      of cells in contrast to results from a less selective ion-exchange system. An
      expanded bed of Cibacron Blue Sepharose Fast Flow was used to purify
      phosphofructokinase from feedstock of disrupted yeast prepared by high pressure
      homogenisation without the need for prior removal of particulate material. The
      potential for the use of expanded beds in large scale purification systems is
      discussed.

PMID- 1387652
TI  - Relationship between the concentrations of estriol sulfate and estrone sulfate in
      human breast cyst fluid.
AB  - Estriol-3-sulfate (E3S) is present in human breast cyst fluid (BCF) in median
      levels of 8.7-10.4 nmol/L, yet is barely detectable in the serum (less than 0.034
      nmol/L). The source of this huge concentration of E3S is unknown. It may
      accumulate from blood by active transport or be synthesized and concentrated
      within the cyst. Since estrone sulfate (E1S) and its possible precursor,
      dehydroepiandrosterone sulfate (DHEAS) are elevated in BCF, E3S may originate via
      16 alpha-hydroxylation of E1S. The present study examined the correlations
      between the levels of DHEAS and E1S with those of E3S in BCF. The sodium and
      potassium ions were also quantified and related to the steroid concentrations. By
      linear regression analysis of log-normalized data there was a highly significant
      correlation between the concentrations of E1S and E3S (n = 355, r = 0.690, P less
      than 0.001) and between DHEAS and E3S (n = 361, r = 0.577, P less than 0.001).
      The BCF were classified according to their K/Na ion ratios: type 1, greater than
      1.0, type II, less than 0.25, and type III, 0.25-1.0. By Student's t test, the
      concentrations of E3S differed between each BCF Type (P less than 0.002). This
      was also true for E1S and DHEAS. Type 1 cysts were associated with the highest
      estrogen sulfate levels and type II with the lowest levels. The possible
      physiological importance of this observation resides in reports that the BCF type
      expressing the highest steroid concentrations has been related to an aporcine
      like epithelial lining of the cyst wall and a somewhat higher risk for developing
      breast cancer. The results suggest that E3S in BCF may originate from E1S, but
      alternate mechanisms are not precluded.

PMID- 1387653
TI  - The ovarian contribution to peripherally derived serum C19 conjugates.
AB  - While serum markers of peripheral androgen metabolism, such as 5 alpha-androstane
      3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) and androsterone glucuronide
      (AoG), have been highly correlated with adrenal androgen production, the relative
      ovarian contribution to the pool of various C19 conjugates has not been fully
      investigated. Our hypothesis was that whereas the ovary may not produce C19
      conjugates directly, ovarian androgens, such as testosterone (T) and
      androstenedione (A), may be used as substrate for peripheral production of these
      conjugates. To determine whether the ovary contributes directly to the pool of
      C19 conjugates, blood was obtained from the ovarian and peripheral veins of eight
      normal women (NW) at hysterectomy. To assess the indirect ovarian contribution to
      C19 conjugate production, the effect of ovarian suppression and stimulation on
      circulating 3 alpha-diol and Ao conjugate levels was examined in 10 NW and 10
      anovulatory nonhirsute patients with PCO (NH-PCO). Ovarian suppression was
      carried out with leuprolide acetate (1 mg, sc) daily until the serum estradiol
      level was 30 pg/mL and was continued thereafter during ovarian stimulation with
      im human menopausal gonadotropin or FSH. Blood samples were taken before, during,
      and after GnRH agonist suppression and just before hCG stimulation. Both
      unconjugated and conjugated androgens were quantified in serum by specific RIAs.
      No peripheral-ovarian gradients were found for 3 alpha-diol or Ao sulfates (3
      alpha-diolS or AoS) or glucuronides. In the NH-PCO group, both T and A levels
      were elevated, and they were suppressed significantly to levels similar those in
      NW. With stimulation, T and A levels rose significantly to higher levels than
      those observed in NW. Both AoS and 3 alpha-diolS, but not AoG and 3 alpha-diolG,
      decreased significantly with agonist suppression in the two groups; the decrease
      in levels of AoS and T correlated significantly in the NH-PCO group. With
      stimulation, the Ao and 3 alpha-diol conjugate levels increased significantly in
      NH-PCO and were most marked for Ao S and 3 alpha-diol S, which were previously
      suppressed; the increase in AoG and A correlated highly. Our data suggest that
      while there is no evidence for the direct ovarian production of C19 conjugates,
      these markers of peripheral androgen action are influenced by precursors from the
      ovary, principally A and T.

PMID- 1387654
TI  - T cell receptor alpha chain polymorphisms in multiple sclerosis.
AB  - Numerous studies have implicated the major histocompatibility complex (MHC) class
      II alleles, DR2 and DQw1, as multiple sclerosis (MS) susceptibility loci,
      however, the involvement of other loci is implied by twin studies and the
      relative lack of haplotype sharing for MHC. To evaluate the role that the TCR
      alpha chain genes may have in MS susceptibility, three variable (V) alpha
      polymorphisms were examined for associations in MS patients. Genotype and allele
      frequencies were compared to four different control groups: unaffected siblings
      and parents of the MS patients, patients with insulin-dependent diabetes mellitus
      (IDDM) and healthy unrelated Caucasians. No significant differences in allele and
      genotype frequencies at these three loci were observed in the MS population
      compared to the control groups. In addition, we analysed the distribution of
      haplotype sharing in affected sibling pairs. Among 30 informative families, there
      was no significant increase in haplotypes shared by affected siblings over that
      expected based on random segregation. Our results do not support suggestions that
      germline TCR alpha chain genes contribute to genetic susceptibility in MS.

PMID- 1387655
TI  - Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin
      and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected
      patients.
AB  - Quinolinic acid (QUIN) is an neurotoxic N-methyl-D-aspartate receptor agonist and
      an L-tryptophan metabolite of the kynurenine pathway. Increased concentrations of
      QUIN occur in both cerebrospinal fluid (CSF) and blood of patients infected with
      human immunodeficiency virus (HIV)-1, particularly those with neurologic
      disturbances. In the present study of HIV-1 infected patients in Walter Reed
      stages 4, 5 and 6, reductions in L-tryptophan accompanied proportional increases
      in L-kynurenine and QUIN in both serum and CSF. Further, close inter-correlations
      exist between QUIN kynurenic acid and L-kynurenine with both beta 2-microglobulin
      and neopterin in CSF and serum. These correlations support the hypotheses that
      the kynurenine pathway is activated in association with inflammation and
      induction of indoleamine-2,3-dioxygenase. There were no relationships between CSF
      QUIN, L-kynurenine or kynurenic acid with the ratio of serum:CSF albumin
      concentrations, which indicates that the increases in CSF QUIN, L-kynurenine or
      kynurenic acid were not dependent on a breakdown of the blood-brain barrier.
      Kynurenic acid is also a kynurenine pathway metabolite that can attenuate the
      excitotoxic effects of QUIN when present in higher molar concentrations. While
      CSF kynurenic acid levels were increased in HIV-1-infected patients, the
      magnitude of the increases were smaller than those of QUIN and the molar
      concentrations of kynurenic acid were consistently lower than QUIN by at least
      one order of magnitude. We conclude that immune activation increases the levels
      of neuroactive kynurenines within the central nervous system of HIV-1-infected
      patients secondary to activation of indoleamine-2,3-dioxygenase.

PMID- 1387656
TI  - Epithelioid haemangioendothelioma of soft tissue after pellet injury.
AB  - An epithelioid haemangioendothelioma developed at the site of injury sustained
      from an air gun pellet 20 years previously in an otherwise healthy 30 year old
      man, suggesting a possible traumatic aetiology in this case.

PMID- 1387658
TI  - Dowling-Degos' disease mimicking chloracne.
AB  - We describe a patient with clinical features that resembled severe chloracne;
      however, histopathologic findings revealed a reticulated pigmented anomaly.
      Innumerable comedones, many cysts, acneiform scarring, and flexural and facial
      pigmentation were noted in this patient, who is a machinist. A serum test for
      polychlorinated biphenyl was negative, which eliminated a diagnosis of chloracne.
      The spectrum of clinical features of the histologically well-defined Dowling
      Degos' disease is discussed; in this disease lesions can be flexural or acral and
      can appear as macules, comedones, or cysts.

PMID- 1387657
TI  - Captopril-induced pemphigus vegetans with Charcot-Leyden crystals.
AB  - A 78-year-old woman developed intertriginous vegetating plaques, mouth ulcers,
      and a cerebriform tongue after 11 months of captopril therapy. Findings of
      clinical, histologic, and immunofluorescence testing were consistent with a
      diagnosis of pemphigus vegetans. In addition, Charcot-Leyden crystals were
      observed within some of the intraepidermal, eosinophilic abscess cavities, which
      were bordered by granular cells undergoing keratinization. The skin lesions
      cleared rapidly after discontinuation of captopril. To the best of our knowledge,
      this report describes the first case of pemphigus vegetans induced by captopril.

PMID- 1387660
TI  - Treating a mandibular condylar fracture in a patient with Huntington's disease.
AB  - This case illustrates the use of a microplate in the open reduction and fixation
      of an intracapsular mandibular condylar fracture in a patient who was unable to
      tolerate a closed reduction because of the nature of her chronic illness. The
      advantages of this method of fracture fixation include early function and
      elimination of intermaxillary fixation, which benefited our patient. This
      technique should be reserved for patients for whom conservative measures are not
      appropriate.

PMID- 1387659
TI  - Peristomal pyoderma gangrenosum.
AB  - A patient with Crohn's disease and peristomal pyoderma gangrenosum is described.
      This patient is unique because she had a rapid response to intralesionally
      injected steroids. This treatment is ideal for peristomal pyoderma gangrenosum
      because it is administered intermittently when the ostomy appliance is changed
      and it does not interfere with adhesion of the device. All 11 cases of peristomal
      pyoderma gangrenosum described in the literature are reviewed.

PMID- 1387661
TI  - Role of Ly-6A/E and T cell receptor-zeta for IL-2 production.
      Phosphatidylinositol-anchored Ly-6A/E antagonizes T cell receptor-mediated IL-2
      production by a zeta-independent pathway.
AB  - Ly-6A/E molecules were originally implicated in regulation of T cell activation
      because anti-Ly-6A/E mAb induce IL-2 production. More recently we have shown that
      anti-Ly-6A/E also inhibits IL-2 production induced by anti-CD3. In the present
      study we used mutant and transfected cell lines that varied in expression of Ly
      6A/E or TCR-zeta to test whether the positive and negative modulations of IL-2
      production by anti-Ly-6A/E occur by distinct mechanisms. Anti-Ly-6A/E inhibited
      anti-CD3-induced IL-2 production for Ly-6E.1-transfected EL4J cells, but did not
      affect IL-2 production of the parental Ly-6A/E-negative EL4J cells. These results
      indicate that TCR-mediated IL-2 production can occur in the absence of Ly-6A/E
      expression and establish that anti-Ly-6A/E-induced inhibition of IL-2 production
      was the result of antibody binding to Ly-6A/E. As expected, MA5.8 (zeta-negative)
      or CT108 (zeta-truncated) variants of the 2B4.11 T cell hybridoma did not produce
      IL-2 when stimulated with anti-Thy-1 or anti-Ly-6A/E mAb. In contrast, anti-Ly
      6A/E inhibited anti-CD3-induced IL-2 production by MA5.8 and CT108. Furthermore,
      anti-Ly-6A/E-induced IL-2 production was restored for zeta-transfected MA5.8.
      Thus, although induction of IL-2 by anti-Ly-6A/E depends on zeta expression,
      inhibition of IL-2 by anti-Ly-6A/E occurs by a zeta-independent mechanism.
      Interestingly, anti-Ly-6A/E, but not anti-Thy-1, inhibited anti-CD3-induced IL-2
      production by MA5.8 and Ly-6E.1-transfected EL4J. Therefore, inhibition of IL-2
      production by anti-Ly-6A/E was not a general property of a mAb binding to a
      phosphatidylinositol-linked molecule, as has been suggested for induction of IL-2
      production. Taken together these data suggest that the molecular mechanisms of
      induction and inhibition of IL-2 production by anti-Ly-6A/E are separable and
      expression of TCR-zeta is one variable that distinguishes these two pathways.

PMID- 1387662
TI  - Heterodimeric complex formation with CD8 and TCR by bispecific antibody sustains
      paracrine IL-2-dependent growth of CD3+ CD8+ T cells.
AB  - During physiologic activation of mature CD8+ T cells, TCR and CD8 bind to the
      same Ag-complexed MHC class I molecule. Thereby, close proximity is induced
      between CD8 and the TCR/CD3 complex. During this engagement, CD8 may deliver TCR
      independent signals via its associated protein tyrosine kinase, p56lck. We
      studied the potential biologic effects of close association between CD8 and
      TCR/CD3 complexes by using a bispecific antibody (bsAb) directed against both TCR
      and CD8 molecules. This hybrid hybridoma (quadroma)-produced bsAb binds as a
      monomeric molecule to CD3+ CD8+ but not CD3+ CD4+ T cells. The bsAb proved
      capable of inducing the cytotoxic effector function of cloned CD3+ CD8+ T cells
      but not of CD3+ CD4+ T cells. When the bsAb was presented to resting T cells by
      monocytes, proliferation of the CD3+ CD4+ but not the CD3+ CD8+ subset of T
      lymphocytes was induced. Parental anti-TCR antibody induced vigorous growth of
      cells of both subsets. Essentially identical results were obtained when bsAb was
      presented in an immobilized fashion. The unresponsiveness of the CD3+ CD8+ T
      cells with respect to mitogenesis could be restored by exogenous rIL-2. The data
      suggest that bsAb-induced activation differs from activation by monospecific anti
      TCR antibody. The former appears to more closely mimic physiologic Ag-induced
      signaling, because it leads to a similar paracrine IL-2-dependent growth pattern.
      The bsAb may, therefore, be instrumental in studying T cell signaling pathways,
      in particular the role of CD8-associated p56lck therein.

PMID- 1387663
TI  - Inducible cell contact signals regulate early activation gene expression during B
      T lymphocyte collaboration.
AB  - B cells get help in the antibody response by presenting processed Ag to Th cells.
      We asked whether the Ag-presenting B cell must induce Th functions before
      receiving help, or whether B cell activation is a direct consequence of T cell
      recognition of Ag on the B cell surface. To obtain a prompt and sensitive
      indication of the receipt of growth signals, we measured mRNA levels of the
      immediate early genes, c-myc and egr-1, in T and B cells separated from Ag
      specific B-T conjugates of normal, resting murine B cells and a Th line. Although
      Ag-dependent increases in B cell c-myc expression occur as early as 2 h after
      conjugation, early c-myc expression in the B cell was also seen when the Th cells
      were activated with immobilized anti-CD3 in the absence of Ag recognition.
      Therefore, T cell activation rather than Ag recognition per se appears to be
      responsible for the early c-myc signal in the B cells. The c-myc response in the
      B cell depends on induction of a contact-dependent helper function in the T cell,
      which is inhibitable by cyclosporin A acting on the T cell. Delivery of contact
      help is not blocked by anti-class II MHC antibody. Contact with activated Th
      cells induces a different pattern of immediate early gene expression from that
      induced by cross-linking the B cell Ag receptor.

PMID- 1387664
TI  - Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural
      killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells.
      Implications for the relationship of NK and T lymphocytes.
AB  - NK cells have been defined as CD3-, CD16+, and/or CD56+ lymphocytes that mediate
      MHC-unrestricted cytotoxicity against certain tumors and virus-infected cells.
      Although CD3 epsilon transcripts have been detected in some NK clones, it has
      generally been thought that NK cells do not express CD3 proteins other than zeta
      which is associated with CD16 (Fc gamma RIII). We demonstrate that adult
      peripheral blood NK cell lines and clones express cytoplasmic CD3 epsilon
      proteins, but not CD3 delta or gamma. CD3 epsilon proteins were detected by
      immunoprecipitation, Western blot analysis, and immunofluorescence using
      antiserum directed against the cytoplasmic domain of CD3 epsilon. Although
      resting, adult peripheral blood NK cells have essentially undetectable levels of
      CD3 epsilon protein, expression was increased substantially after activation. In
      contrast to adult NK cells, NK cell clones established from human fetal liver
      express CD3 gamma, delta, and epsilon protein subunits that associate and form
      CD3 epsilon, gamma and CD3 epsilon, delta complexes in the cytoplasm, but are
      apparently unable to be transported to the cell surface. These results indicate
      that expression of CD3 gamma delta epsilon subunits is not restricted to T
      lymphocytes and supports the possibility that NK and T cells may be derived from
      common origins.

PMID- 1387666
TI  - Antigen receptor-mediated anergy in resting T lymphocytes and T cell clones.
      Correlation with lymphokine secretion patterns.
AB  - The goal of these studies was to define the stimuli and factors that control the
      induction of anergy in unimmunized resting T lymphocytes. Initial experiments,
      aimed at establishing the system, showed that exposure of Th1 but not Th2 clones
      to immobilized anti-CD3 leads to a block in autocrine growth factor production
      and proliferation upon subsequent restimulation with Ag+APC. Anergy is not
      prevented by accessory cells, suggesting that this model of T cell tolerance may
      be due to receptor-mediated inhibitory signals, independent of costimulatory
      molecules. Culture of small (resting) unimmunized T lymphocytes with anti-CD3 +/-
      IL-2 induces unresponsiveness to restimulation with anti-CD3, but culture with
      anti-CD3+IL-4, which stimulates the differentiation of resting cells into IL-4
      producers, does not induce anergy. Thus, IL-4-producing clones and bulk
      populations of IL-4-producing T cells are resistant to Ag receptor-mediated
      inhibitory stimuli. These results provide experimental models for studying the
      mechanisms of anergy in normal, unselected, mature T cells, and demonstrate
      fundamental similarities between cloned cell lines and unimmunized T lymphocytes
      in the induction of anergy.

PMID- 1387665
TI  - A Na(+)-dependent Ca2+ exchanger generates the sustained increase in
      intracellular Ca2+ required for T cell activation.
AB  - Movement of extracellular Ca2+ is required for the sustained increase in [Ca2+]i
      necessary for T cell activation. However, the mechanisms mediating mitogen
      stimulated Ca2+ movement into T cells have not been completely delineated. To
      explore the possibility that a Na(+)-dependent Ca2+ (Na+/Ca2+) exchanger might
      play a role in the mitogen-induced increases in [Ca2+]i required for T cell
      activation, the effects of inhibitors of this exchanger were examined. Inhibitors
      of Na+/Ca2+ exchange suppressed the sustained increase in [Ca2+]i stimulated by
      ligation of the CD3-TCR complex, but did not affect mobilization of intracellular
      Ca2+ stores. Consistent with the importance of this prolonged increase in [Ca2+]i
      in T cell activation, Na+/Ca2+ exchange inhibitors, but not inhibitors of the
      Na+/H+ antiporter, inhibited DNA synthesis stimulated by immobilized anti-CD3
      mAb. Inhibition only occurred when the agents were present during the first hours
      after stimulation. These agents also inhibited IL-2 production, but not
      expression of the IL-2R or of an early activation Ag, 4F2. Inhibition of IL-2
      production did not account for the inhibition of T cell proliferation as addition
      of exogenous IL-2 or phorbol ester (PDB) did not overcome the inhibition. In
      contrast, activation pathways that are not thought to require an increase in
      [Ca2+]i such as IL-1 + PDB or engagement of CD28 in the presence of PDB were less
      sensitive to the suppressive effects of inhibitors of Na+/Ca2+ exchange. Thus,
      proliferation induced by these stimuli was not suppressed by low concentrations
      of these inhibitors and IL-2 production induced by mAb to CD28 + PDB was not
      inhibited by any concentration of inhibitors of Na+/Ca2+ exchange. These results
      suggest that stimulation of a Ca2+ transporter with the same spectrum of
      inhibition as the Na+/Ca2+ exchanger in other tissues mediates the sustained
      increase in [Ca2+]i required for T cell activation after CD3 ligation.

PMID- 1387667
TI  - Mapping of an inducible element in the T cell receptor V beta 2 promoter.
AB  - The murine V beta 2 promoter was analyzed for an element regulating phorbol ester
      inducibility of the TCR beta chain gene. In transient expression analysis of 5'
      nested deleted fragments of the V beta 2 promoter, the TPA-inducible element
      mapped between -85 and -42. The -85 to -62 oligo conferred 12-0
      tetradecanoylphorbol-13-acetate (TPA) inducibility to the heterologous TPA
      uninducible thymidine kinase promoter. The -85 to -62 region contained an AP-1
      site (-85 to -72) and inverted repeat motif (-72 to -62). The AP-1 site required
      the 3' flanking inverted repeat region for conferring optimal inducibility. In
      vitro transcribed and translated jun/fos heterodimers bind to the V beta 2 AP-1
      motif with a 16-fold lower affinity as compared to the collagenase AP-1 motif.
      This explains the inability of the V beta 2 AP-1 motif to confer optimal TPA
      inducibility by itself. The affinity of jun/fos heterodimers for the V beta 2 AP
      1 motif was not increased by the presence in cis of the inverted repeat motif.
      The 3' flanking inverted repeat binds the ets transactivator but not jun/fos
      heterodimers. The demonstrated cooperativity between the AP-1 and the 3' flanking
      sequence to confer TPA inducibility can thus be explained by the individual
      contributions of jun/fos and ets transactivators.

PMID- 1387668
TI  - Peptide binding to soluble HLA-DR4 molecules produced by insect cells.
AB  - HLA-DR4Dw4 molecules were expressed in insect Sf9 cells. The transmembrane and
      cytoplasmic domains of the DR4 alpha- and beta-chains were replaced by the
      carboxy terminal sequence of decay accelerating factor, leading to a phosphatidyl
      inositol glycan membrane anchor. This structure contains a cleavage site for
      phosphatidyl inositol-specific phospholipase C, allowing efficient solubilization
      of the rDR4 molecules. We present evidence that infected insect cells express
      properly associated surface heterodimers and are able to present antigenic
      peptides to DR4Dw4-restricted T cell clones. Phosphatidyl inositol-specific
      phospholipase-cleaved recombinant molecules exhibited in vitro binding
      characteristics similar to DR4 molecules purified from lymphoblastoid cells. In
      terms of peptide specificity, pH optimum, kinetics, and affinity they were
      indistinguishable within the limits of our assay system. However, the peptide
      binding capacity of the recombinant molecules was higher than that of native DR4
      molecules.

PMID- 1387669
TI  - Human IL-1 receptor antagonist promoter. Cell type-specific activity and
      identification of regulatory regions.
AB  - To study the molecular mechanisms involved in transcriptional regulation of the
      human IL-1R antagonist (IL-1ra) we have isolated 1680-bp of 5'-flanking region
      DNA from the IL-1ra gene. This region of DNA was sequenced and cloned into the
      luciferase expression vector pA3Luc (pRA-1680.Luc) for use in gene transfer
      studies aimed at determining the cis-acting DNA elements required for IL-1ra
      expression. Sequence analysis of the IL-1ra promoter revealed a TATAA box at -26,
      with consensus sequences for possible NF-kB-, NFIL-1 beta A-, AP-1-, and CRE
      binding sites located further upstream. When transfected into a variety of human
      and murine cell lines, the cloned IL-1ra promoter was preferentially active in
      those cell lines in which expression of the endogenous IL-1ra gene could be
      detected. The cloned promoter and the endogenous IL-1ra promoter utilized the
      same transcriptional start site. This promoter activity was LPS-inducible in the
      RAW 264.7 murine macrophage cell line. In the human monocytic cell line U937, IL
      1ra promoter activity was inducible by LPS or PMA treatment, but the combination
      of LPS and PMA led to the greatest increase in promoter activity, identical to
      the pattern of expression of endogenous IL-1ra mRNA as detected by polymerase
      chain reaction analysis. A series of 5'-truncated promoter constructs having a
      common 3'-end at +27 were created to map potential cis-acting transcriptional
      elements important for full IL-1ra promoter activity. Removal of sequences
      between -294 and -148 led to a greater than 90% decrease in both unstimulated and
      LPS-induced promoter activity; further deletion to -85 led to an almost complete
      abrogation of promoter activity. These studies demonstrate that the cloned IL-1ra
      promoter behaves in a manner consistent with that of the endogenous gene. Two
      regions within the IL-1ra promoter are identified which are required for full
      promoter activity.

PMID- 1387670
TI  - Regulation by transforming growth factor-beta 1 of expression and function of the
      receptor for IFN-gamma on mouse macrophages.
AB  - Transforming growth factor-beta (TGF-beta) is known phenomenologically as a
      negative regulator of several functions of mouse bone marrow macrophages. The
      studies reported here extend this list by showing that TGF-beta can suppress
      cytolytic activity of mouse bone marrow culture-derived macrophages that already
      have become activated by IFN-gamma and LPS for tumor cell killing, as well as
      confirm that this cytokine can interfere with the induction of activation.
      Suppression was caused by a shift in the dose response curve for IFN-gamma rather
      than absolute inhibition; the 50% effective dose for IFN-gamma was increased
      approximately fourfold by treatment with TGF-beta. TGF-beta also decreased the
      absolute number of IFN-gamma R on the surfaces of pretreated macrophages by
      approximately 30 to 35%, without altering the affinity with which IFN-gamma
      bound. The increased concentration of IFN-gamma needed to produce the higher
      level of receptor occupancy explained the observed shift in the IFN-gamma dose
      response curve. These results suggest that TGF-beta mediates its negative
      regulatory effects on macrophage activation by interfering with coupling of the
      IFN-gamma R to the pathways that induce and maintain macrophage activation for
      tumor cell killing. Such effects are consistent with the view that TGF-beta is a
      negative regulator of macrophage activation for tumor cell killing. Because of
      this fact, neoplastic cells that secrete this cytokine may have a distinct
      survival advantage.

PMID- 1387671
TI  - Potential role of monocyte chemoattractant protein 1/JE in monocyte/macrophage
      dependent IgA immune complex alveolitis in the rat.
AB  - We have examined the role of monocyte chemoattractant protein 1 (MCP 1) in the
      pathogenesis of monocyte/macrophage-dependent IgA immune complex alveolitis in
      the rat. Rat MCP 1 was cloned and expressed in order to facilitate analysis of
      its function in rat models of human disease. A cDNA library was constructed from
      rat pulmonary artery endothelial cells stimulated with TNF-alpha. The cDNA
      library was screened with synthetic oligonucleotide probes based on the recently
      published rat MCP 1 cDNA sequence. Among numerous MCP 1-positive clones, four
      full length (approximately 480 bp) cDNA were rescued, amplified by polymerase
      chain reaction, and ligated into a pJVETLZ baculovirus transfer vector.
      Spodoptera frugiperda insect cells (Sf-21) infected with baculovirus recombinants
      (Auto-grapha california nuclear polyhedrosis virus) bearing properly oriented MCP
      1 cDNA (AcMCP 1) directed the expression of unique peptides of 18, 21, and 23
      kDa. Treatment of AcMCP 1-infected Sf-21 cells with tunicamycin resulted in
      reduced production of the 21- and 23-kDa proteins and an increase in 16- to 18
      kDa products, the predicted size range of uncleaved and nonglycosylated rat MCP
      1. Denatured and refolded 23-kDa and 21-kDa rat MCP 1 species exhibited dose
      dependent monocyte-specific chemotactic activity at concentrations as low as 10(
      10) M whereas the 18-kDa species exhibited negligible activity. Antibodies that
      react with the immunoblot, block rat rMCP 1-directed monocyte chemotaxis, and
      neutralize monocyte-specific chemotactic activity secreted by TNF-stimulated rat
      endothelial cells were raised in rabbits immunized with the 23-kDa MCP 1 species.
      Intravenous administration of anti-MCP 1 antibodies upon initiation of IgA immune
      complex lung injury resulted in a marked reduction in lung injury as measured by
      pulmonary vascular permeability, alveolar hemorrhage, and pulmonary
      monocyte/macrophage recruitment and pulmonary monocyte/macrophage recruitment.
      These data suggest that MCP 1 may play an important role in the pathogenesis of
      monocyte/macrophage-dependent IgA immune complex alveolitis in the rat.

PMID- 1387672
TI  - Induction of tumor necrosis factor-alpha production by mast cells via Fc gamma R.
      Role of the Fc gamma RIII gamma subunit.
AB  - Murine mast cells produce cytokines in response to cross-linking of high affinity
      receptors for IgE (Fc epsilon RI). Murine mast cells also express the two types
      of low-affinity receptors for IgG, murine (m)Fc gamma RII, and mFc gamma RIII. We
      examined the ability of mFc gamma R to trigger a cytokine response such as TNF
      alpha production by mast cells. We found that the mFc gamma RII- and mFc gamma
      RIII-positive mouse mastocytoma cells MMC-1 released TNF-alpha when challenged
      with F(ab')2 fragments of the rat anti-mFc gamma RII/III 2.4G2 mAb and mouse anti
      rat IgG F(ab')2. The release of TNF-alpha was preceded by an increase in TNF
      alpha transcripts. mFc gamma RII and mFc gamma RIII have 95% homologous
      extracellular domains but unrelated transmembrane and intracytoplasmic (IC)
      domains. mFc gamma RII are single chain receptors whereas mFc gamma RIII
      associate with a homodimeric gamma-chain that also associates with Fc epsilon RI
      and TCR. In order to analyze the ability of mFc gamma RII and III to trigger the
      synthesis of TNF-alpha, we studied RBL-2H3 cells transfected with corresponding
      cDNA. Rat basophilic leukemia (RBL) transfectants expressing mFc gamma RIII
      produced TNF-alpha in response to 2.4G2 F(ab')2, but not transfectants expressing
      mFc gamma RII. Non-transfected RBL cells and mFc gamma RII- or mFc gamma RIII
      expressing transfectants, however, released TNF-alpha in response to a rat IgG2a
      mAb. The respective roles of the alpha and gamma subunits of mFc gamma RIII were
      examined by studying the production of TNF-alpha by RBL cells expressing deletant
      and chimeric mFc gamma R. The deletion of intracellular amino acids of the Fc
      gamma RIII alpha subunit did not prevent 2.4G2 F(ab')2 from triggering the
      synthesis of TNF-alpha. The substitution of the IC domain of mFc gamma RII for
      that of mFc gamma RIII gamma, but not that of Fc gamma RIII alpha, enabled 2.4G2
      F(ab')2 to trigger the release of TNF-alpha by RBL transfectants. A cytokine
      response can therefore be induced in mouse and rat mast cells through Fc gamma R.
      This response is triggered upon cross-linking of mFc gamma RIII but not mFc gamma
      RII. It depends on the IC sequences of the gamma but not of the alpha subunit of
      mFc gamma RIII.

PMID- 1387674
TI  - Clinical use of sufentanil as an anesthetic.
AB  - This review considers a few of the controversies and most recent data pertaining
      to the clinical intraoperative use of the potent opioid sufentanil. Although
      sufentanil is used extensively as the opioid component of "balanced" anesthesia,
      opioids themselves are not total anesthetics. Sufentanil is effective in reducing
      the so-called stress responses that can occur with balanced anesthesia. Although
      no conclusive data have shown that such reduction in stress response improves
      anesthetic outcome, many clinicians continue to choose sufentanil for both
      convenience and improved hemodynamic control. Recent pharmacokinetic modeling
      suggests that sufentanil would be a good choice for balanced anesthesia.
      Additionally, initial postoperative analgesia appears to work better when
      sufentanil rather than fentanyl is used intraoperatively. Although cost
      considerations remain important, cost analysis would suggest that, on a per
      patient basis, choice of intraoperative opioid has very little effect on total
      hospital costs.

PMID- 1387673
TI  - Increased production of antigen-specific B lymphocytes during in vitro
      immunization using carrier-specific T helper hybridomas.
AB  - An in vitro method to increase the production of hapten-specific antibody-forming
      B cells (AFC) using a carrier-specific T helper hybridoma and murine splenocytes
      is described. Naive splenocytes (6 x 10(6)/ml) are cultured in vitro in the
      presence of a hapten-carrier conjugate (DNP.OVA) and OVA-specific T helper
      hybridomas (0.5 x 10(6)/ml). After 4-5 days in vitro immunization (IVI), the
      maximum number of DNP-specific AFC were found using a spot-ELISA with twice the
      number of IgM positive cells as IgG positive AFC. The presence of antigen in the
      form of a hapten-carrier complex and the use of a carrier-specific Th hybridoma
      resulted in more hapten-specific AFC than when neither antigen nor Th hybridoma
      were present or when antigen alone or T help alone were used. Also when the
      hapten was conjugated to a carrier not recognised by the carrier-specific Th
      hybridoma there were considerably fewer (less than 50%) hapten specific AFC
      formed. When in vivo primed splenocytes (DNP) were boosted in vitro (IVB) under
      the same conditions as for IVI most hapten-specific AFC were found on day 4 and
      both anti-DNP IgM and IgG AFC were increased relative to IVI. Again most AFC were
      found when hapten was bound to the relevant carrier. In conclusion, carrier
      specific T hybridomas can be used in an in vitro immunization procedure with
      naive or primed splenocytes to increase the frequency of anti-hapten AFC. This
      method offers an improvement over the current in vitro immunization procedures
      for the production of monoclonal antibodies.

PMID- 1387675
TI  - Alterations in the proton ATPase activity of rat liver mitochondria after
      hemorrhagic shock.
AB  - To clarify the damage site of complicated oxidative phosphorylation function
      after hemorrhagic shock in jaundiced liver mitochondria, the proton adenosine
      triphosphatase complex (H(+)-ATPase) activity of inside-out submitochondrial
      particles, mitochondrial membrane potential, and oxygen consumption in the
      presence of uncoupler were studied as indices of phosphorylation, membrane
      intactness, and oxidation, respectively. Hemorrhagic shock was induced according
      to the Wiggers' model (mean arterial blood pressure = 40 mm Hg) in rats made
      jaundiced by common bile duct ligation; rats that had undergone sham operations
      served as controls. After reinfusion of the shed blood, all of the control rats
      survived, but all of the jaundiced rats died. Liver mitochondria from jaundiced
      rats after 1 hour of hypotension demonstrated a 48% decrease in mitochondrial
      ATPase activity without remarkable changes in either oxidative activity or
      membrane potential of liver mitochondria. The reduction of ATPase activity
      appeared to be due to its release in the supernatants obtained from
      submitochondrial particles, because the ATPase activity of supernatants in
      jaundiced rats was significantly (p less than 0.001) higher than that of the
      controls. It is suggested that this enzyme plays a key role in energy restoration
      in recovery from shock.

PMID- 1387676
TI  - Congenital syphilis presenting as desquamative dermatitis.
AB  - During the last 5 years the incidence of congenital syphilis has increased
      several-fold and reached epidemic proportions. This increase is directly related
      to a similar increase in cases of primary and secondary syphilis in women and has
      been linked to the use of "crack" cocaine. Factors responsible for the increase
      in reported cases of congenital syphilis include poor prenatal care,
      implementation of new surveillance case definition, failure to perform
      serological tests, treatment failures with benzathine penicillin, and maternal
      reinfection. Clinical manifestation of congenital syphilis are multisystemic but
      are often absent at birth. We report a case of congenital syphilis missed at
      birth and later characterized by prominent desquamative dermatitis affecting most
      of the skin surface.

PMID- 1387677
TI  - Chronic infusion of quinolinic acid in rat striatum: effects on discrete neuronal
      populations.
AB  - The intrastriatal infusion of relatively low doses of quinolinic acid (Quin, 4-10
      nmol/h) for 1 or 2 weeks induced time-dependent degeneration of neuronal cells.
      We examined the effects of these infusions on discrete cellular populations. The
      distribution of somatostatin (SOM)-positive neurons labelled by
      immunocytochemistry or by NADPH-diaphorase histochemistry and of cholinergic
      cells stained by acetylcholinesterase was quantified in the peripheral portion of
      the lesioned area. SOM-positive cells did not appear selectively spared by Quin
      infusion. The proportion of SOM- and NADPH-diaphorase-positive neurons killed by
      exposure to Quin was similar to or higher than the percentage of total neurons
      degenerated (from 30 to 85%). A selective sparing of cholinergic cells was
      observed in all conditions examined; perfusion of 6 nmol/h for a week induced 65%
      of cell death while not more than 30% of cholinergic neurons were killed. Thus,
      the neurochemical similarity between the degenerative effects of intrastriatal
      Quin and Huntington's disease (HD) did not appear confirmed by the chronic
      perfusion of low doses of Quin for SOM-positive neurons, whereas an analogy
      between Quin's effects and HD was suggested by the pattern of AChE staining.

PMID- 1387678
TI  - Evolution of muscle specific proteins in Werdnig-Hoffman's disease.
AB  - The pattern of expression of desmin, vimentin, titin and different myosin
      isoforms expressed in atrophic and hypertrophic type I and type II muscle fibers
      was investigated in 7 biopsies from patients of various ages all diagnosed as
      suffering from Werdnig-Hoffman's disease. The results revealed that there was a
      progressive atrophy affecting both type I and type II muscle fibers. The
      proportion of atrophic type II fibers increased with age. These atrophic fibers
      expressed predominantly fast MHC together with variable amounts of embryonic and
      fetal abnormal concentrations of desmin, vimentin and titin were also observed in
      some of these fibers. Hypertrophic type I fibers expressed exclusively slow MHC.
      These results are in good agreement with the hypothesis that Werdnig-Hoffman's
      disease is associated with a persistence of slow twitch type I motor units and a
      loss of phasic type II motor units. They also confirm that the atrophic fibers
      were frequently immature although embryonic MLC was never detected in these
      muscles. In addition we have demonstrated that the hypertrophic fibers were not
      completely normal since they frequently contained abnormal concentrations of
      desmin and titin at their periphery.

PMID- 1387679
TI  - Down's syndrome: occurrence of ALZ-50 reactive neurons and the formation of
      senile plaques.
AB  - We have histopathologically investigated the hippocampal formation in 4
      individuals with Down's syndrome (DS), 7 control individuals, and 3 individuals
      dying after being in coma 3-7 days. Adjacent sections of brain were stained by
      the Bielschowsky method and by ALZ-50 immunocytochemical methods. ALZ-50
      immunoreactive neurons were found in each individual with DS and only in the
      control infants. Neither ALZ-50-immunoreactive features nor abnormal silver
      positive features stained by the Bielschowsky method were found in the adolescent
      or young adult controls or coma patients. Diffuse form senile plaques (SP) were
      found only in the oldest DS individual. The data suggest that ALZ-50 reactive
      neurons persist during the life of an individual with DS and may precede the
      formation of SP.

PMID- 1387681
TI  - Effects of teicoplanin on human platelet aggregation in vitro and ex vivo.
AB  - The effects of teicoplanin on adenosine-diphosphate (ADP)-induced human platelet
      aggregation in vitro and on both ADP- and ristocetin-induced human platelet
      aggregation ex vivo were investigated. In the in vitro study carried out on
      platelets from 7 healthy volunteers, teicoplanin had no effect on platelet
      function even at a concentration (1 mg/ml) 10 times higher than the peak level
      found in the in vivo state, but at the highest concentration (10 mg/ml), which is
      100 times higher than that reached in vivo, it inhibited ADP-induced platelet
      aggregation. In the ex vivo studies carried out in 10 healthy volunteers,
      teicoplanin, following single intravenous doses of 400 mg and 800 mg, did not
      produce any effect on platelet function up to 6 hours after administration. After
      12 hours, teicoplanin, when given at 800 mg i.v., reduced ADP-induced platelet
      aggregation.

PMID- 1387680
TI  - The effect of mixed bovine brain gangliosides on hypoxic conduction block in
      control and streptozotocin-diabetic rats.
AB  - This study describes the electrophysiological responses of endoneurial
      preparations derived from rat sciatic nerve to acute hypoxia in vitro.
      Preparations from control rats exhibited a 40% decline in compound action
      potential (CAP) amplitude after 40 min exposure to medium gassed with 8% O2. In
      preparations from 4 week streptozotocin-diabetic rats CAP declined by only 29%,
      indicating a resistance to hypoxic conduction blockade. Treating diabetic rats
      with mixed bovine brain gangliosides (10 mg/kg/day i.p.) exaggerated this
      resistance to hypoxic conduction blockade as CAP amplitude fell to only 18% of
      initial values. In a separate experiment, treating non-diabetic rats with
      gangliosides (10 mg/kg/day i.p.) or adding gangliosides (400 micrograms/ml)
      directly to the medium in which control nerves were maintained during in vitro
      recording also significantly attenuated the decline in CAP amplitude after 40 min
      hypoxia, thus effectively inducing a resistance to hypoxic conduction blockade
      similar to that observed in nerves from diabetic rats. These studies demonstrate
      that the systemic or acute local administration of gangliosides induces a
      resistance to hypoxic conduction block in normal nerve and exaggerates the
      resistance to hypoxic conduction block of diabetic rats.

PMID- 1387682
TI  - Prospective validation of a single sample technique to determine technetium-99m
      MAG3 clearance.
AB  - Technetium-99m-MAG3 clearance is proportional to OIH clearance and can be used
      directly as a measure of renal function. Multiple plasma sample, two-compartment
      clearance data from three studies were recently pooled to develop a single-sample
      regression equation for determining the clearance of 99mTc-MAG3. To test this
      published equation, a prospective study was conducted in 34 patients with a wide
      range of renal function. Multiple plasma samples were obtained from 9 to 60 min
      following the bolus injection of 99mTc-MAG3 and the clearances were calculated
      based on a single injection, two-compartment model. Clearances were also
      calculated using a single 43-min plasma sample and the published regression
      equation. There was an excellent correlation (r = 0.976) between the two
      clearances; the slope of the regression line was 1.01 with an intercept of -26.6;
      the standard error of the estimate was 24 ml/min. In conclusion, the current
      regression equation provides a good estimate of 99mTc-MAG3 clearance.

PMID- 1387683
TI  - Left ventricular hypertrophy versus hypertrophic cardiomyopathy.

PMID- 1387684
TI  - Evidence for changes in adrenal and testicular steroids during HIV infection.
AB  - The serum levels of cortisol, progesterone, 17 alpha-hydroxyprogesterone,
      dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione (delta 4),
      testosterone (T), estrone, and estradiol of HIV+ men and HIV- men were determined
      by radioimmunoassay. The cortisol, 17 alpha-hydroxyprogesterone, and estrone
      levels of all HIV+ subjects were 35-55% (p less than 0.01), 25-90% (p less than
      0.01), and 30-50% (p less than 0.01) higher, respectively, than those of
      controls. Androgen levels were very high in Centers for Disease Control (CDC)
      groups II and III of HIV infection (DHEA, 85%, p less than 0.01; delta 4, 60%, p
      less than 0.01; T, 30%, p less than 0.05), but much lower in group IVC1 and IVC2.
      The estradiol levels were significantly elevated only in group IVD (50%, p less
      than 0.01) and group IVC2 (25%, NS). These results indicate that serum hormone
      levels are correlated with HIV infection group. The changes in steroid hormone
      concentrations during the development of HIV infection may have important
      implications for the immune response of patients. The high cortisol and estrone
      levels of all groups, the elevated androgen levels in asymptomatic groups, and
      the low androgens in AIDS patients may form part of the complex network of
      immunomodulatory factors.

PMID- 1387685
TI  - Beta-hexosaminidase splice site mutation has a high frequency among non-Jewish
      Tay-Sachs disease carriers from the British Isles.
AB  - In the course of defining mutations causing Tay-Sachs disease (TSD) in non-Jewish
      patients and carriers from the British Isles, we identified a guanine to adenine
      change (also previously described) in the obligatory GT sequence of the donor
      splice site at the 5' end of intron 9 of the hexosaminidase alpha peptide gene.
      Of 24 unrelated mutant chromosomes from 20 non-Jewish subjects (15 TSD carriers,
      four TSD patients, and one TSD fetus), five had mutations common in the Ashkenazi
      Jewish community, and 10 had the intron 9 splice site mutation. This is an
      unexpected result considering the diverse origin of the population of the British
      Isles. This mutation was not found in 28 control UK subjects or 11 Jewish
      carriers of known TSD mutations. Before attempting detection of unknown
      mutations, non-Jewish TSD carriers from the British Isles should be screened for
      the intron 9 donor splice site mutation as well as those mutations which
      predominate in the Jewish community.

PMID- 1387686
TI  - A neutron solution scattering study of the structure of annexin-V and its binding
      to lipid vesicles.
AB  - Low-angle neutron solution scattering has been used to study the structure of
      annexin-V and its interaction with small single-bilayer vesicles consisting of
      phosphatidylserine and phosphatidylcholine at a 33:66 (mol:mol) ratio. There was
      no evidence for a change in the state of aggregation of annexin-V, which remained
      as a monomer in the presence of 3 mM-free calcium. The only difference between
      presence and absence of free calcium was the increase of the radius of gyration,
      from 19(+/- 0.4) A to 22(+/- 0.4) A in 2H2O buffer and from 19.7(+/- 1.2) A to
      22.2(+/- 1.2) A in H2O buffer. The relative molecular weight, outer radius and
      average surface area per lipid of vesicles alone were respectively 2.5(+/- 0.5) x
      10(6), 127 A and 90(+/- 19) A2. These parameters were not modified in the
      presence of free calcium, which testified to the absence of vesicle coalescence.
      The calcium-dependent binding of annexin-V was essentially interfacial and
      therefore did not alter significantly the structural characteristics of the
      vesicles. At saturation, 80(+/- 10) annexin-V molecules were bound per vesicle,
      the available area per molecule being 2500(+/- 300) A2 thus covering
      approximately 28 lipid head groups. The protein shell was approximately 35 A
      thick. The apparent dissociation constant was probably less than 1 nM. These data
      contribute to a more accurate definition of annexin-V as a possible probe of
      those cytodynamic events involving exposure of sequestered membrane
      aminophospholipids.

PMID- 1387687
TI  - A cDNA clone encoding the ADP/ATP translocase of Drosophila melanogaster shows a
      high degree of similarity with the mammalian ADP/ATP translocases.
AB  - A complementary DNA clone encoding the ADP/ATP translocase in Drosophila
      melanogaster has been identified. It has been shown by sequence analysis to
      contain a single open reading frame that encodes a polypeptide 297 amino acids
      long. This polypeptide shows extensive similarities to the known eukaryotic
      translocase polypeptides, the similarity being greatest (up to 80% identity) to
      the mammalian ADP/ATP translocases. In situ hybridization to polytene chromosomes
      of D. melanogaster with the sequence characterized in this study showed
      localization at a single site on the X chromosome at 9E. DNA transfer
      hybridization experiments suggest that more than one gene coding for the ADP/ATP
      translocase is present in the D. melanogaster genome.

PMID- 1387688
TI  - Does anaerobic threshold correlate with maximal lactate steady-state?
AB  - The aim of this study was to compare the 'anaerobic threshold' (AnT) of subjects
      determined during a continuous 2-min incremental exercise test until exhaustion
      and the 'maximal lactate steady-state' (BLaSsmax) determined during prolonged
      exercise at constant loads corresponding to the subjects' AnT and/or 5-25% above
      and below it. Seventeen subjects performed an incremental exercise test and 1-5
      prolonged exercise tests on a cycle ergometer until exhaustion at intervals of 1
      week, and work rates, oxygen uptake (VO2) values and brachial venous blood
      lactate (BLa) levels were measured. It was proposed that when exercising at a
      constant workload below AnT, BLa would fall after having reached its peak; at the
      level of AnT, BLa reaches maximal steady-state (BLaSsmax); and above AnT, BLa
      increases continuously. Altogether, in 34 of 45 tests with a constant workload
      between 80 and 125% AnT, BLa values were as expected. In those cases in which
      BLaSsmax was reached, BLa increased on average by 3.8 mM from resting levels.
      This increase was 2.0 mM greater than that seen between resting levels and AnT
      during incremental exercise. There was no correlation between BLa values at
      BLaSsmax and at AnT, both when expressed as an increase in BLa (delta BLa) and
      absolute BLa concentration. Altogether, 81% of the variation in BLa concentration
      at BLaSsmax could be explained by the subjects' age, the percentage of slow
      twitch fibres and BLa levels at rest. The AnT and BLaSsmax did not differ
      significantly, and these values were correlated (r = 0.83). Together, AnT and age
      accounted for 85% of the variation seen in BLaSsmax. The BLaSsmax did not
      correlate with AnT when fixed at a BLa concentration of 4 mM (AnT4mM). The three
      hypotheses tested in this study were confirmed, and the present results
      demonstrate that AnT correlates with BLaSsmax. The few exceptions to anticipated
      BLa kinetics were small in magnitude and could be explained by physiological
      variations.

PMID- 1387689
TI  - [Long-term results of the surgical treatment of complicated inguinal hernias].
AB  - The results of 473 hernioplastic operations performed in 397 patients with
      complex inguinal hernia within the period of from 1958 to 1988 have been
      analysed. In followup of from 2 to 30 years, 3 (0.75%) patients developed a
      disease recurrence because of errors in technique of kapron plasty of the
      anterior wall of the inguinal canal. From 1970, in the clinic for plasty of
      complex inguinal hernia, a coarse mesh lavsan prosthesis of the own construction
      has been used. There were no disease recurrences.

PMID- 1387690
TI  - [One-stage laparoscopic cholecystectomy and appendectomy].
AB  - The authors describe the technique of simultaneous performance of cholecystectomy
      and appendectomy with the use of laparoscopic technique. A standard set of
      laparoscopic instruments of the firm "Karl Shtortz" (FRG) and conventional points
      for introduction of the instruments into the abdominal cavity were used. The
      immediate and long-term result of the intervention is favourable.

PMID- 1387691
TI  - Microbiologically monitored fumigation of a newly built SPF laboratory rodent
      facility.
AB  - The initial sanitization and sterilization of a newly built animal facility for
      the breeding and holding of specific pathogen free (SPF) rats and mice is
      described. The fumigation programme was started with methyl bromide treatment
      directed primarily against arthropods, followed by ammonia spray to kill
      coccidial oocysts and concluded by three formaldehyde treatments with fog and
      spray against bacteria and viruses. The practicalities and problems involved are
      described in detail and the rationale and purpose of the programme and its
      monitoring are discussed. The report is expected to contribute towards the
      establishment of a rational, efficient and standardized fumigation programme for
      SPF animal facilities, under increasing constraints of safety and environmental
      considerations concerning pollution with toxic and corrosive agents.

PMID- 1387692
TI  - Human GM-CSF receptor alpha-chain gene is highly polymorphic but not rearranged
      in AML.
AB  - Acute myeloid leukaemia (AML) blast cells express haemopoietic growth factor
      receptors. However, their presence does not predict response to the cognate
      ligand in vitro. This suggests that haemopoietic growth factor receptor structure
      or function may be abnormal in some cases of acute myeloid leukaemia. The
      granulocyte-macrophage colony-stimulating factor receptor alpha-chain gene (GM
      CSF-R) has recently been localised to the pseudoautosomal region of the sex
      chromosomes. A sex chromosome is lost in 25% of cases of AML FAB subtype M2. The
      loss of one allele of this gene may have some aetiological significance in AML if
      the other allele is altered leading to abnormal receptor structure, function or
      number. In this initial study, we have examined DNA from leukaemic cells of 29
      patients with AML, including three with FAB subtype M2 with deletion of an X or Y
      chromosome for evidence of gross rearrangement of this gene. We report that
      although the gene is highly polymorphic for a number of restriction enzymes, we
      have found no evidence of gross rearrangement in AML.

PMID- 1387693
TI  - Effects of an IL-1 receptor antagonist on acute myeloid leukemia cells.
AB  - The effect of an interleukin 1 receptor antagonist (IL-1ra) on the proliferation
      of acute myelogenous leukemia (AML) cells was investigated. The antagonist
      reduced the spontaneous clonogenicity of these cells as well as the clonogenicity
      of these cells subsequent to exposure to the antagonist. The effects of the IL
      1ra on the clonogenicity of leukemia cells was observed even when the antagonist
      failed to inhibit DNA synthesis by the leukemia cell population as a whole. The
      data are consistent with the concept that the administration of IL-1ra subsequent
      to cytotoxic therapy has the potential of slowing the regrowth of leukemia cells
      thereby potentiating the effects of chemotherapy.

PMID- 1387694
TI  - Monoclonal antibody Ki-67 identifies B and T cells in cycle in chronic
      lymphocytic leukemia: correlation with disease activity.
AB  - Ki-67 is a monoclonal antibody that recognises a nuclear antigen expressed during
      most phases of the cell cycle. We have analysed, by immunocytochemistry, the
      frequency, morphology, and clinical significance of Ki-67+ cells in 108 patients
      with B-cell chronic lymphocytic leukemia (CLL). Because in normal peripheral
      blood Ki-67+ cells are mainly T lymphocytes, we have also investigated, by double
      immunoenzymatic staining, the proportion of Ki-67+ T cells (Ki-67/CD3+) in CLL.
      Four groups of patients were identified: (i) 47 with stage A, (ii) 32 with stages
      B + C, (iii) 24 with greater than 10% of circulating prolymphocytes (CLL/PL) and
      (iv) five with Richter's syndrome. Within stage A CLL, two groups were
      considered: A' (Hb greater than or equal to 12 g/dl and lymphocytes less than 30
      + 10(9)/l) and A" (Hb less than 12 g/dl or lymphocytes greater than or equal to
      30 x 10(9)/l). The percentage and absolute number of Ki-67+ leukemic cells was
      found to increase with the stage of the disease and correlate with the proportion
      of prolymphocytes. On the other hand, the proportion of Ki-67+ T cells (CD3+) was
      significantly higher in patients with CLL stage A' (29.3 +/- 4.5), which includes
      patients with long-standing, stable disease, than in CLL stage A" (9.5 +/- 3.3),
      B + C (7.1 +/- 4.6), and CLL/PL (6.4 +/- 2.8). Ki-67 seems to identify patients
      with more aggressive forms of CLL, such as CLL/mu 2PL with more than 10% Ki-67+
      cells (25% of the cases) and Richter's syndrome, in which all the large lymphoma
      cells are Ki-67+. Long-term follow-up will establish whether Ki-67 is a good
      prognostic marker and can predict disease outcome.

PMID- 1387695
TI  - Current issues in hypertension. Old questions with new answers and new questions.
AB  - Hypertension is a systemic vascular disease that makes its mark upon the "target
      organs"--heart, brain, and kidneys--through the hemodynamic hallmark of the
      disease, a progressively increasing vascular resistance to the forward flow of
      blood. The effect of pressure overload upon the heart is one of concentric
      hypertrophy of the left ventricle that is, in turn, associated with an
      independent risk of morbidity and mortality. Reduction of arterial pressure
      reverses the risk associated with the elevated arterial pressure and also
      diminishes the risk from hemorrhagic and thrombotic strokes. Why the risk of the
      interaction of hypertensive and atherosclerotic diseases can be reduced on the
      brain but not as impressively on the heart remains to be learned, but certain
      recent lines of clinical and experimental evidence point to some answers. The
      issue as to why, in the face of increasing numbers of patients receiving the
      benefits of therapy, there is an alarming increase in patients with end-stage
      renal disease defies more imagination and study. Thus, many of the old questions
      seem to be achieving some meaningful answers; but associated with these new
      answers we are confronted with new questions.

PMID- 1387696
TI  - Current issues in advanced heart failure.
AB  - In the past 50 years, an increased understanding of the pathophysiologic
      mechanisms associated with the development of heart failure has produced a more
      precise treatment of this syndrome. The effects of the agents used for the
      treatment of patients with advanced heart failure have been summarized in this
      article and demonstrate the importance of vasodilatory drugs on the survival and
      progression of dilated cardiomyopathy.

PMID- 1387697
TI  - Partial correction of impaired creatine kinase activity in diabetic rat heart by
      physical training.
AB  - The effect of physical training on total creatine kinase (CK), CK-MM, and CK-MB
      isoenzyme activity was studied in hearts of diabetic and control rats. Diabetes
      was induced with streptozotocin (50 mg/kg), and only rats with blood glucose
      levels between 14 and 22 mmol/L 1 week later were kept in the protocol. Exercise
      training was performed on a treadmill in a progressive 10-week program. Physical
      training did not induce any significant changes in plasma glucose or insulin
      levels in diabetic rats. Total CK, CK-MM, and CK-MB activity was decreased in
      diabetic rat heart by 27%, 22%, and 56%, respectively. Physical training did not
      induce any important changes in CK activity in heart of nondiabetic rats.
      However, in diabetic rat heart, training increased total CK activity by 13%, CK
      MM activity by 12%, and CK-MB activity by 31%. We conclude that the decrease in
      cardiac CK activity observed in chronic experimental diabetes mellitus can be
      partly alleviated by a program of physical training. This may be one of the
      mechanisms whereby physical conditioning improves cardiac function in
      experimental diabetes.

PMID- 1387698
TI  - Effects of salt loading on glucose tolerance, blood pressure, and albuminuria in
      rats with non-insulin-dependent diabetes mellitus.
AB  - We studied the effects of salt loading on glucose tolerance, blood pressure, and
      albuminuria in rats with mild non-insulin-dependent diabetes mellitus (NIDDM).
      Two-day-old male Wistar Kyoto (WKY) rats were injected intraperitoneally (IP)
      with either 75.0 mg/kg streptozotocin (STZ) or vehicle as control. Salt loading
      was performed as 1% NaCl of drinking solution from 4 weeks until 12 weeks of age
      (estimated sodium intake: control, 3.14 +/- 0.28 mEq/d in tap-water group, 11.9
      +/- 0.95 mEq/d in salt-loaded group; NIDDM, 2.93 +/- 0.16 mEq/d in tap-water
      group, 12.0 +/- 2.59 mEq/d in salt-loaded group). Oral glucose tolerance,
      glycosylated hemoglobin (GHb), and pancreatic insulin content at 12 weeks did not
      differ between the salt-loaded group and tap-water group in both NIDDM and
      control rats. Urinary sodium excretion was increased in salt-loaded groups of
      control and NIDDM rats, but systolic blood pressure did not differ among the
      groups (control, 151 +/- 6 mm Hg in tap-water group, 150 +/- 3 mm Hg in salt
      loaded group; NIDDM, 152 +/- 3 mm Hg in tap-water group, 157 +/- 2 mm Hg in salt
      loaded group). Urinary albumin excretion was significantly increased in salt
      loaded groups (1,790 +/- 272 micrograms/d in control, 1,617 +/- 174 micrograms/d
      in NIDDM rats) compared with tap-water groups (691 +/- 75 micrograms/d in
      control, P less than .05; 616 +/- 69 micrograms/d in NIDDM rats, P less than
      .001), irrespective of STZ injection, but endogenous creatinine clearance was not
      different among the groups. Furthermore, renal growth was more greatly increased
      in salt-loaded groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387700
TI  - Laparoscopic adrenalectomy in Cushing's syndrome and pheochromocytoma.

PMID- 1387699
TI  - Lipoprotein(a): its inheritance and molecular basis of its atherothrombotic role.
AB  - Lipoprotein(a) or Lp(a), is a member of the plasma lipoproteins with general
      properties of LDL but with a protein moiety represented by apoB100 disulfide
      linked to apolipoprotein(a) or apo(a). Apo(a) is polymorphic in size; at present
      a total of 11 isoforms have been reported, but more are likely to be identified
      in view of the fact that at least 19 alleles of the apo(a) gene have recently
      been reported. There are remarkable variations in the plasma Lp(a) levels; but
      uncertainties still exist about the factors responsible for this variability.
      High plasma Lp(a) levels have been associated with an increased incidence of
      cardiovascular disease, mainly based on epidemiological evidence. Both
      atherogenic and thrombogenic potentials have been suggested; the first
      attributable to the LDL-like properties of Lp(a) and the other to the plasminogen
      like characteristics of apo(a). From the mechanistic viewpoint in vitro studies
      suggest that the thrombogenic action may occur at the level of the endothelium
      whereas Lp(a) that localizes in the sub-endothelial intima is expected to undergo
      complexation with matrix components and favor the formation of the
      atherosclerotic plaque. How Lp(a) polymorphism relates to the postulated
      cardiovascular pathogenicity of this lipoprotein remains to be established.

PMID- 1387701
TI  - Healing waters.

PMID- 1387702
TI  - Compensating work-related injury.

PMID- 1387703
TI  - The management of a dental abscess in a patient with acute intermittent
      porphyria. A case report.
AB  - The case of a 40-year-old white woman with a periapical abscess of pulpal origin
      and the medical condition of acute intermittent porphyria is described. The oral
      and dental management of the case with reference to complications, etiology, and
      symptoms of acute intermittent porphyria is reviewed.

PMID- 1387704
TI  - Ondansetron HCL (Zofran TM, Glaxo).

PMID- 1387705
TI  - Promoting normal development in school-age children and adolescents who are
      technology dependent: a family centered model.
AB  - Normal life experiences foster development and encourage psychological and social
      competence in children. This article describes a family-centered approach to
      developmental assessment and intervention with the aim of normalizing the life
      experiences of school-age children and adolescents who are dependent on or
      assisted by medical technology.

PMID- 1387706
TI  - New federal policy for children with special health care needs: implications for
      pediatricians.
AB  - Title V of the Social Security Act of 1935 established the nation's first
      categorical health care program for children: the Crippled Children's Service. In
      1985, federal legislation changed the name of the Crippled Children's Service to
      the Program for Children With Special Health Care Needs. Four years later, new
      amendments to Title V dramatically altered the Program's mission. States are now
      required to spend 30% of the funds from the Maternal and Child Health Services
      block grant on children with special health care needs and to take specific steps
      toward improving the service system for these children and their families. The
      new mandate is the only current foundation of a national health policy for
      children with special health care needs. The 1989 law substantially broadens the
      mission of the state programs and explicitly recognizes that all children with a
      special health care need should have access to an appropriate, community-based
      system of care monitored by state Children with Special Health Care Needs
      agencies. In addition, states are now required to conduct needs assessments
      pertaining to these children, to foster local systems of care, and to ensure a
      high quality of community-based services. Understanding the implications of the
      new amendments is essential because pediatricians and other child health care
      professionals have key roles to play in implementing these new policies.

PMID- 1387707
TI  - Emesis as a complication of cancer chemotherapy: pathophysiology, importance, and
      treatment.
AB  - Up to 30% of patients receiving chemotherapy experience uncontrolled nausea and
      vomiting despite pharmacotherapeutic advances. Currently marketed agents used to
      treat these symptoms are compared. Dose escalation of these agents may improve
      response rates. Recent focus has been on a new class of antiemetics, the
      serotonin antagonists. Ondansetron, currently the only serotonin antagonist with
      Food and Drug Administration approval for treatment of chemotherapy-induced
      emesis, demonstrates the efficacy and potential advantages of this class of
      antiemetics.

PMID- 1387708
TI  - [Comparative study of the structure and protein composition of spermatozoid
      centrioles from sturgeons and salmon].
AB  - The aim of the present work was to compare the structure and protein composition
      of centrioles from spermatozoa of sturgeon and salmon fishes. The total protein
      content of the extracted fractions was studied by Na-SDS electrophoresis.
      Proteins with molecular weights from 15 to 170 kDa were detected. In both cases
      the major protein of centrioles is a protein with a molecular weight equal to
      that of tubulin. A protein with the molecular weight corresponding to actin was
      also detected. In both cases the ATPase activity stimulated by Ca2+ and Mg2+ ions
      was revealed. Electron microscopic studies showed differences in the
      ultrastructure of centrioles from sturgeon and salmon spermatozoa.

PMID- 1387709
TI  - Karyoplasmic interaction selection strategy: a general strategy to detect protein
      protein interactions in mammalian cells.
AB  - We describe a strategy and reagents for study of protein-protein interactions in
      mammalian cells, termed the karyoplasmic interaction selection strategy (KISS).
      With this strategy, specific protein-protein interactions are identified by
      reconstitution of the functional activity of the yeast transcriptional activator
      GAL4 and the resultant transcription of a GAL4-regulated reporter gene.
      Reconstitution of GAL4 function results from specific interaction between two
      chimeric proteins: one contains the DNA-binding domain of GAL4; the other
      contains a transcriptional activation domain. Transcription of the reporter gene
      occurs if the two chimeric proteins can form a complex that reconstitutes the DNA
      binding and transcriptional activation functions of GAL4. Using the KISS system,
      we demonstrate specific interactions for sequences from three different pairs of
      proteins that complex in the cytoplasm. In addition, we demonstrate that reporter
      genes encoding cell surface or drug-resistance markers can be specifically
      activated as a result of protein-protein interactions. With these selectable
      markers, the KISS system can be used to screen specialized cDNA libraries to
      identify novel protein interactions.

PMID- 1387710
TI  - ATP-driven Ca2+/H+ antiport in acid vesicles from Dictyostelium.
AB  - Amoebae of the cellular slime mold Dictyostelium discoideum possess an extensive
      and dynamic endomembrane system that includes many types of acidic vacuoles. A
      light membrane fraction from Dictyostelium, rich in vacuolar-type H(+)-ATPase,
      has been described [Padh, H., Lavasa, M. & Steck, T.L. (1989) J. Cell Biol. 108,
      865-874]. Here, we show that this "acidosomal" fraction also contains a high
      affinity vanadate-sensitive Ca2+ uptake activity that is stimulated by the pH
      gradient formed by the H(+)-ATPase. We attribute this Ca2+ uptake to the presence
      of a H(+)-countertransporting Ca(2+)-ATPase, pumping Ca2+ into an acidic
      compartment.

PMID- 1387711
TI  - Composition of transcription factor B-TFIID.
AB  - Initiation of transcription by RNA polymerase II requires a TFIID factor, which
      can recognize the TATA element common to many promoters. Two distinct
      multisubunit TFIID factors can be resolved from extracts of mammalian cells, and
      both of them contain the well-characterized TATA-binding protein (TBP) and are
      capable of supporting RNA polymerase II transcription in an in vitro reaction
      system. The smaller complex, B-TFIID, was purified and its subunit composition
      was determined. B-TFIID consists of two subunits: the TBP and a TBP-associated
      factor (TAF) of 170 kDa. This TAF is specific for B-TFIID and appears not to be
      present in the D-TFIID complex. Furthermore, it was found that the highly
      purified B-TFIID fractions have (d)ATPase activity.

PMID- 1387712
TI  - Growth factors and vitamin E modify neuronal glutamate toxicity.
AB  - The sympathetic nerve cell line PC-12 is killed by glutamate in a concentration
      dependent manner. Although glycine and the deletion of magnesium weakly
      potentiate glutamate toxicity and PC-12 cells express N-methyl-D-aspartate
      receptor mRNA, most toxicity is mediated by means of a mechanism independent of
      typical N-methyl-D-aspartate receptors. Glutamate toxicity is, however, greatly
      enhanced by prior exposure to nerve growth factor or basic fibroblast growth
      factor. Glutamate killing is blocked by epidermal growth factor and, to a lesser
      extent, by vitamin E. These observations show that synergistic interactions
      between growth factors and excitotoxic amino acids may play critical roles in the
      developing nervous system and that antioxidants attenuate this toxicity.

PMID- 1387713
TI  - Analysis of dynamin isoforms in mammalian brain: dynamin-1 expression is
      spatially and temporally regulated during postnatal development.
AB  - In adult rat brain, the microtubule-associated protein dynamin is composed of a
      closely spaced polypeptide doublet of approximately 100 kDa. Using an antibody
      preparation that is monospecific for dynamin-1 (the higher molecular mass
      isoform) we examined the temporal and regional expression of dynamin-1 in
      developing rat brain. Analysis of whole rat brain homogenates established that
      prior to postnatal day 9, dynamin-1 was present only at very low levels and
      thereafter its expression steadily increased with adult levels being attained by
      postnatal day 23. In individual regions of the brain, dynamin-1 levels were
      highest in cortex, amygdala, and striatum, significantly lower in olfactory bulb,
      cerebellum, and midbrain, and lowest in brainstem. During postnatal development,
      each of the regions exhibited approximately the same time course of protein
      expression except for a slight lag in expression in olfactory bulb. The spatial
      and temporal patterns of expression of dynamin-1 correlate with the establishment
      and/or maintenance of mature neuronal structure and function rather than
      dendritic or axonal outgrowth.

PMID- 1387714
TI  - New cloning vectors for integration in the lambda attachment site attB of the
      Escherichia coli chromosome.
AB  - A set of plasmid cloning vectors has been constructed, allowing the integration
      of any DNA fragment into the bacteriophage lambda attachment site attB of the
      Escherichia coli chromosome. The system is based upon two components: (i) a
      number of cloning vectors containing the lambda attachment site attP and (ii) a
      helper plasmid, bearing the lambda int gene, transcribed from the lambda PR
      promoter under the control of the temperature-sensitive repressor cI857. The DNA
      fragment of interest is cloned into the multicloning site of one of the attP
      harboring plasmids. Subsequently, the origin of the plasmid, located on a cloning
      cassette, is cut out and the DNA becomes newly ligated, resulting in a circular
      DNA molecule without replication ability. The strain of choice, containing the
      int gene carrying helper plasmid, is transformed with this DNA molecule and
      incubated at 42 degrees C to induce int gene expression. Additionally, the
      temperature shift leads to the loss of the helper plasmid after a few cell
      generations, because the replication ability of its replicon is blocked at 42
      degrees C. These vectors have been successfully used for integration of several
      promoter-lacZ fusions into the chromosome. The ratio between integration due to
      homologous recombination and Int protein-mediated integration has been
      determined.

PMID- 1387715
TI  - Induction of Fc epsilon RII/CD23 on PHA-activated human peripheral blood T
      lymphocytes and the association of Fyn tyrosine kinase with Fc epsilon RII/CD23.

PMID- 1387716
TI  - The role of CD23 and its receptor in T-cell/B-cell interaction: implications for
      regulation of IgE synthesis.

PMID- 1387717
TI  - Evidence for a CD23 counterstructure other than IgE.

PMID- 1387718
TI  - Murine soluble Fc epsilon RII: a molecule in search of a function.

PMID- 1387719
TI  - sCD23 in the control of T-lymphocyte development.

PMID- 1387720
TI  - The role of soluble CD23 on normal and leukaemic myeloid precursor cells.

PMID- 1387721
TI  - CD23 and eosinophils.

PMID- 1387722
TI  - Fc epsilon RII/CD23 on epidermal Langerhans' cells.

PMID- 1387723
TI  - [Diagnostic imaging of non Q myocardial infarction].

PMID- 1387724
TI  - [Measurements of plasmin-alpha 2 plasmin inhibitor complex and FDP.D dimer levels
      in the fibrinolytic therapy of acute pulmonary thromboembolism].
AB  - The key enzyme for fibrinolysis is plasmin, which is converted from plasminogen
      by plasminogen activator. Activated plasmin lyses fibrinogen and fibrin to make
      fibrin degradation products(FDPs) and plasmin is inactivated immediately by alpha
      2 plasmin inhibitor. As FDP.D dimer is derived solely from insoluble fibrin,
      FDP.D dimer is thought of as an index for clot lysis. We measured plasmin-alpha 2
      plasmin inhibitor complex(PIC) and FDP.D dimer plasma levels in 3 patients with
      acute pulmonary thromboembolism treated with recombinant tissue plasminogen
      activator(tPA). Fifteen million units of tPA(TD-2061) were infused in one hour on
      the first, second and third hospital days. PIC and FDP.D dimer before tPA
      infusion showed slightly elevated values as compared to normal ranges. They
      increased markedly after tPA infusion. These findings suggest that the
      fibrinolytic system is slightly activated in the acute phase of pulmonary
      thromboembolism and also strongly activated by tPA infusion. Increased FDP D
      dimer suggests that fibrin clots are dissolved by activated plasmin. Improvement
      of arterial oxygen tension was observed after tPA infusion. As sustained higher
      FDP.D dimer means the existence of fibrin clots, heparin treatment should be
      continued for prevention of clot formation as long as FDP.D dimer shows higher
      value. In conclusion, PIC and FDP.D dimer are useful indices not only to detect
      the activated state of the fibrinolytic system but also to know clot lysis in tPA
      treatment.

PMID- 1387725
TI  - From pathology to physiology of the human T-lymphocyte receptor.
AB  - The recent description of a selective human CD3 gamma deficiency and other T-cell
      receptor (TCR)/CD3 structural and functional defects, together with previous
      biochemical data on the structure and interactions of the TCR/CD3 complex, may
      aid in elucidating the physiology of this multi-subunit membrane ensemble. CD3
      gamma seemed to be required for the commitment and thymic maturation of an
      important fraction of T lymphocytes to the CD8 (but not CD4) lineage, perhaps by
      participating with the CD8 co-receptor in the instructive signal delivered
      through the alpha beta TCR during intrathymic positive selection by HLA class I
      molecules. The homologous CD3 delta component would, in contrast, be necessary
      for the selection of CD4 lymphocytes by HLA class II molecules. The interaction
      of CD4 and CD8 with the TCR/CD3 complex during antigen recognition may thus be
      asymmetrical, taking place through CD3 delta and gamma, respectively. Also, the
      existence of in vivo functional TCR/CD3 hemireceptors (lacking either CD3 gamma
      or CD3 delta) is suggested, and defects in their relative amount on the T-cell
      surface may disrupt unresponsiveness to self antigens and generate autoimmunity.

PMID- 1387726
TI  - Effect of rIFN-gamma on antibody-mediated cytotoxicity via human monocyte IgG Fc
      receptor II (CD32).
AB  - Human monocytes and macrophages express an isoform of IgG Fc receptor II (Fc
      gamma RII), Fc gamma RIIa. Two allotypic variants of this receptor could be
      distinguished with respect to their ability to bind murine (m)IgG1 complexes
      either strongly or weakly, defined as high-responder (HR) and low-responder (LR),
      respectively. We investigated the effect of recombinant (r)IFN-gamma on the
      ability of freshly isolated monocytes, and those cultured for 40 h and 9 days, to
      mediate antibody-dependent cell-mediated cytotoxicity (ADCC). Using human
      erythrocytes (E) sensitized with mIgG1 as target cells, Fc gamma RII was studied
      selectively. Cells which had been cultured for 40 h exhibit a significantly
      decreased Fc gamma RII expression, and Fc gamma RII-mediated ADCC activity as
      compared with freshly isolated monocytes. Co-culture with rIFN-gamma (40 h)
      reversed this decrease. Short-term rIFN-gamma-cultured cells, and fresh cells
      express similar numbers of Fc gamma RII, and exhibit comparable Fc gamma RII
      mediated ADCC activity. Phagocytic activity was not affected. Prolonged culture
      of monocytes for 9 days, co-cultured with rIFN-gamma either from day 0 or from
      day 7, did not affect expression or functional activity of Fc gamma RII.
      Furthermore, the effects were observed in both HR and LR individuals. Our results
      show that rIFN-gamma has strong effects on Fc gamma RII-mediated responses
      specifically during the early stages of monocyte maturation, most likely by
      affecting receptor expression levels.

PMID- 1387727
TI  - Expression of CD11b (Leu15) antigen on CD3+, CD4+, CD8+, CD16+ peripheral
      lymphocytes. Estimation of CD3+8+11b+ and CD3+4-8-11b+ T-cell subsets using a
      single laser flow cytometer.
AB  - CD11b (Leu15) epitope is expressed on 20-30% of peripheral blood lymphocytes,
      including CD16+ large granular lymphocytes and CD8+ cells. This study confirms
      that 30% of CD8+ lymphocytes and virtually all CD16+ NK cells from healthy
      subjects express this determinant. In parallel, our data show that various
      proportions of CD3+4-8-, TCR-delta cytotoxic T lymphocytes and occasionally CD4+
      lymphocytes subsets could also express this epitope. The CD8+11b+ phenotype is
      associated with suppression of T-cell proliferative response and has been
      extensively used to characterize suppressor T lymphocytes. Since about 25% of CD8
      lymphocytes are non-T (CD3-) and express the CD16 NK antigen (CD8+16+3-), the
      expression of CD11b was also studied on CD8+3+ T-cell and CD8+16+ NK-cell
      subsets. To this end, we developed three methods using a flow cytometer equipped
      with a single laser and two fluorescence detectors. Results showed that T
      CD8+3+11b+ and NK CD8+16+11b+ lymphocytes account for 30% and 70% of CD8+11b+
      cells respectively. Consequently, the CD8+3+11b+ phenotype would be more specific
      for suppressor T lymphocytes than the total CD8+11b+ phenotype which includes
      high proportions of CD16+ NK cells.

PMID- 1387729
TI  - Reporting about people with disabilities.

PMID- 1387728
TI  - Production of a suppressor of lymphocyte proliferation by two human oral
      carcinoma cell lines.
AB  - This study examined the production of an immunosuppressive factor by the KB and
      H191 human oral squamous carcinoma cell lines. Conditioned media (CM) from both
      cell lines markedly inhibited mitogen- and alloantigen-induced proliferation of
      normal human and rat peripheral blood lymphocytes. By contrast, the proliferation
      of an exponentially-growing fibroblast cell line remained unchanged by CM. The
      immunosuppressive factor appeared to act after lymphocyte commitment as indicated
      by continued blast cell formation, the failure of CM to suppress resting
      lymphocytes and the fact that CM caused maximum inhibition of lymphocyte
      proliferation 72 h after the addition of PHA. The addition of exogenous IL-2 did
      not counteract lymphocyte suppression. Inclusion of indomethacin and isoniazid
      during cell culture did not significantly alter the degree of suppressive
      activity. Mycoplasma contamination was absent and CM did not act directly with
      the thymidine or mitogen. The factor was heat stable at 50 degrees C, acid labile
      and had a molecular weight in excess of 300 kDa. The results demonstrate that
      human oral squamous carcinoma cell lines produce an immunosuppressive factor that
      may have a role in tumour evasion of the host immune response.

PMID- 1387730
TI  - Tentoxin sensitivity of chloroplasts determined by codon 83 of beta subunit of
      proton-ATPase.
AB  - Tentoxin is a naturally occurring phytotoxic peptide that causes seedling
      chlorosis and arrests growth in sensitive plants and algae. In vitro, it inhibits
      activity of the beta subunit of the plastid proton-adenosine triphosphatase
      (ATPase) from sensitive species. Plastid atpB genes from six closely related,
      tentoxin-sensitive or -resistant Nicotiana species differ at codon 83, according
      to their response to the toxin: glutamate correlated with resistance and
      aspartate correlated with sensitivity. The genetic relevance of this site was
      confirmed in Chlamydomonas reinhardtii by chloroplast transformation. The alga,
      normally tentoxin-resistant, was rendered tentoxin-sensitive by mutagenesis of
      its plastid atpB gene at codon 83. Codon 83 may represent a critical site on the
      beta subunit that does not compete with nucleotide binding or other catalytic
      activities.

PMID- 1387731
TI  - The met proto-oncogene receptor and lumen formation.
AB  - The met proto-oncogene product (Met) and its ligand, hepatocyte growth
      factor/scatter factor (HGF/SF), have been implicated in cell mitogenic response,
      cell motility, and the promotion of the ordered spatial arrangement of tissue. By
      means of confocal laser-scanning microscopy, it was shown that Met is expressed
      in cells bordering lumen-like structures that resemble ducts in the human mammary
      cell line T47D. In human breast tissue biopsies, Met staining was intense in
      normal cells bordering mammary ducts but was reduced in adjacent tumor tissue.
      Met staining in lumen-forming organs colocalizes with staining of antibody to
      phosphotyrosine, which suggests that the Met receptor and its substrates may be
      activated in lumen structures or ducts. HGF/SF treatment of human epithelial
      carcinoma cell lines resulted in the formation of lumen-like structures in vitro.
      Reduced expression of Met could be related to the extent of tumor cell
      differentiation.

PMID- 1387732
TI  - The endosurgery evolution: no place for sacred cows.

PMID- 1387733
TI  - Retrospective and prospective multi-institutional laparoscopic cholecystectomy
      study organized by the Society of American Gastrointestinal Endoscopic Surgeons.

PMID- 1387734
TI  - Laparoscopic cholecystectomy for complicated gallstone disease.
AB  - After performing selectively 25 laparoscopic cholecystectomies (LC) to determine
      the place of LC in the management of complicated gallstones, all patients
      presenting with gallstones were evaluated by the authors for LC. Eighty-six
      consecutive patients were evaluated and 84 were studied. Follow-up in every case
      exceeded 6 months. In three of 10 patients with acute cholecystitis, LC was not
      possible; each had a history longer than 48 h and all had gangrene of the
      gallbladder. In four patients with empyema, LC was successful, but operative
      cholangiography failed. Operative cholangiography was successful in 76 of the
      remaining 77. Of eight patients suspected of having stones in the CBD,
      cholangiography excluded stones in six and confirmed them in two. Cholangiography
      identified three other patients with totally unsuspected CBD stones. Of the five
      patients with CBD stones, four had them flushed to the duodenum at LC following
      transcystic balloon dilatation of the papilla and one had a post-op. ERCP. Of
      four patients with acute pancreatitis, three had LC in the same admission. LC was
      possible in all three patients with morbid obesity. We conclude that with
      experience, LC is possible for complicated gallstones. In acute cholecystitis,
      the probability of success is higher with earlier operative intervention.
      Operative cholangiography is essential. It not only identifies unsuspected CBD
      stones but also allows LC without ERCP in those with suspected CBD stones and
      with modification it allows treatment of those stones.

PMID- 1387735
TI  - Laparoscopic splenectomy.
AB  - Splenectomy has traditionally been done through a generous laparotomy incision,
      requiring complete mobilization of the spleen for removal. In selected cases,
      however, splenectomy may either be facilitated or performed entirely by
      laparoscopic means. Two patients with Hodgkin's disease in whom splenectomy was
      facilitated laparoscopically are described; in another patient with idiopathic
      thrombocytopenic purpura (ITP), the splenectomy was successfully performed
      through the trocar incisions. In selected cases, laparoscopic splenectomy is
      feasible, provided the laparoscopist is expert in advanced techniques of
      intraabdominal endoscopic surgery.

PMID- 1387736
TI  - Laparoscopic cholecystectomy in the obese patient.
AB  - Between September 1990 and September 1991 laparoscopic cholecystectomy (LC) was
      performed in 310 patients with symptomatic cholelithiasis by using a four-cannula
      technique. Of this group, 282 were normal or overweight (group A) and 28 were
      obese (group B) according to classification using the Body Mass Index. Forty-one
      patients had cholecystitis of varying degree. There were no deaths in this
      series. The conversion rate to laparotomy was 2.9% and the morbidity was 5.4%.
      There was no statistical difference between groups A and B in relation to the
      length of procedure, conversion rate, or morbidity. This small series suggests
      that laparoscopic access is still feasible, if at times difficult, in obese
      patients. Specific surgical techniques concerning instrument length and cannula
      placement that may be useful in obese patients are described.

PMID- 1387737
TI  - Laparoscopic cholecystectomy in a renal transplant recipient.
AB  - Laparoscopic cholecystectomy is a viable and safe alternative for the treatment
      of symptomatic gallstones and biliary colic. As surgeons gain more experience
      with this procedure, contraindications become fewer and indications increase.
      Well-documented advantages of this approach include less patient discomfort, less
      surgical scarring, and earlier return to employment. Not previously discussed in
      the literature, however, are the additional advantages that this procedure holds
      for a specific subset of patients--namely, those patients that have undergone
      successful organ transplantation and are receiving immunosuppressive drugs. We
      report a case of a laparoscopic cholecystectomy in such a patient.

PMID- 1387738
TI  - A safe and simple method to maintain a clear field of vision during laparoscopic
      cholecystectomy.
AB  - A clear field of vision during laparoscopic cholecystectomy was attained by using
      a newly designed retractor which elevates the abdominal wall and does not require
      high-pressure CO2 infusion into the peritoneal cavity. As the abdominal cavity is
      continuously ventilated, smoke from the cauterization is suctioned off through
      openings in the middle part of the retractor. There is no interference with
      placement of ports.

PMID- 1387739
TI  - A prospective randomized trial of laparoscopic versus open appendectomy.
AB  - BACKGROUND: Laparoscopic appendectomy is feasible, but whether it confers any
      advantage to patients with acute appendicitis is not known. We performed a
      randomized controlled trial to compare results of laparoscopic and open
      appendectomy in patients with signs and symptoms suggesting acute appendicitis
      who were seen by one surgical team. METHODS: Sixty-two consecutive patients were
      randomized, 30 to laparoscopy and 32 to a classical open appendectomy.
      Postoperative recovery, complications, and return to normal activities were
      compared in the two groups. RESULTS: The laparoscopy group were discharged
      earlier (2.5 vs 3.8 days, p less than 0.01). Postoperative complications were
      more frequent after open appendectomy. Follow-up showed less pain, shorter bed
      stay at home, and faster return to work and sport after laparoscopic
      appendectomy. CONCLUSIONS: This prospective randomized study shows that
      laparoscopic appendectomy is superior to open appendectomy in terms of hospital
      stay, postoperative complications, and return to normal activities and is
      recommended as the approach of choice in the management of acute appendicitis.

PMID- 1387740
TI  - Mucociliary function, ciliary ultrastructure, and ciliary orientation in Young's
      syndrome.
AB  - BACKGROUND: Mucociliary clearance is impaired in patients with Young's syndrome
      (obstructive azoospermia with recurrent sinobronchial disease), cystic fibrosis,
      and primary ciliary dyskinesia. No defect of cilia or mucus has been detected in
      Young's syndrome. METHODS: Ciliary function and ultrastructure, including ciliary
      orientation, were studied quantitatively in 20 patients with Young's syndrome and
      20 normal subjects to determine the incidences of ciliary defects. Nasal ciliated
      epithelium was obtained from each subject and used for measurement of ciliary
      beat frequency and ultrastructural analyses. Ciliary orientation was determined
      by measuring ciliary deviation in electron micrographs; ciliary deviation is a
      measure of the relative orientation of cilia in relation to each other in which
      high values indicate ciliary disorientation. RESULTS: Ciliary beat frequency and
      the incidence of microtubular defects and numbers of dynein arms did not differ
      between patients with Young's syndrome and control subjects. In patients with
      Young's syndrome basal ciliary deviation (16.0 degrees) was similar to that in
      control subjects (14.1 degrees), but at the ciliary tip ciliary deviation (21.9
      degrees) was greater than in healthy subjects (14.5 degrees). CONCLUSION: The
      relative disorientation of the distal ciliary axoneme in patients with Young's
      syndrome compared with normal subjects may be due to a structural defect but is
      more likely to be a consequence of abnormal mucus.

PMID- 1387741
TI  - Characterization of thromboxane A2/prostaglandin H2 receptors in porcine coronary
      artery--the inhibitory effect of a novel dibenzoxepin derivative, KW-3635.
AB  - We characterized the thromboxane A2/prostaglandin H2 receptors in porcine
      coronary artery. The binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to
      coronary arterial membranes was saturable and displaceable. Scatchard analysis of
      equilibrium binding showed a single class of high affinity binding sites with a
      dissociation constant of 18.5 +/- 1.0 nM and the maximum binding of 80.7 +/- 5.2
      fmol/mg protein. [3H]SQ 29,548 binding was concentration-dependently inhibited by
      thromboxane A2 antagonists such as SQ 29,548, BM13505 and BM13177 or the
      thromboxane A2 agonists such as U46619 and U44069. KW-3635, a novel dibenzoxepin
      derivative, concentration-dependently inhibited the [3H]SQ 29,548 binding to
      thromboxane A2/prostaglandin H2 receptors in coronary artery with an inhibition
      constant of 6.0 +/- 0.69 nM (mean +/- S.E.M.).

PMID- 1387742
TI  - Validation of two in vitro test systems for estrogenic activities with
      zearalenone, phytoestrogens and cereal extracts.
AB  - In order to establish alternatives to the frequently used uterotropic assay with
      mice, defined estrogen-sensitive cell lines (MCF-7 cells and LeC-9 cells) were
      used to determine the estrogenic activities of purified compounds of vegetable
      origin (myco- and phytoestrogens) and zearalenone-contaminated forage cereals
      (wheat, barley and oats). In MCF-7 cells, a human breast cancer cell line, the
      induction of an estrogen-specific exoprotein served as a parameter of estrogenic
      activities. LeC-9 cells represent a genetically transformed cell clone derived
      from mouse L-cells. Here, hormone-like activities were measured by the expression
      of the bacterial chloramphenicol acetyltransferase (CAT) gene under the control
      of an estrogen-responsive element. Toxic effects affecting cell viability were
      monitored in this system by the expression of a second reporter gene (the
      bacterial beta-galactosidase gene controlled by the constitutive human beta-actin
      promoter). Relative estrogenic activities of myco- and phytoestrogens determined
      with both systems are concomitant, but higher as compared to the uterotropic
      assay with mice.

PMID- 1387743
TI  - In vitro formation of testosterone via the delta 5-pathway in the human umbilical
      cord.
AB  - Homogenates of two groups of term umbilical cord (n = 6, 37-40 weeks; n = 6, 38
      40 weeks) were separately incubated with [7n-3H]pregnenolone and [1,2,6,7
      3H]dehydroepiandrosterone. Using the reverse-isotope dilution technique,
      [3H]dehydroepiandrosterone and [3H]testosterone formed from the respective
      substrates were isolated and characterized. The extent of enzymic conversions
      were 0.015-0.28% and 0.044-2.2%. These results provide evidence for the metabolic
      transformation of pregnenolone to testosterone via the delta 5-3 beta-hydroxy
      route.

PMID- 1387744
TI  - Neonatal tolerance induction in the thymus to MHC-class-II-associated antigens.
      V. Thymus medulla and the site for deletional signaling achievement in Mls
      tolerance.
AB  - Intravenous (i.v.) injection of Mls-1a peritoneal cavity (PerC) cells from
      (BALB/c x AKR)F1 (Mls-1b/a, H-2d/k) mice into newborn BALB/c (Mls-1b, H-2d) mice
      induced thymus cell tolerance by one week of age, accompanied by V beta 6+ cell
      elimination. The tolerant state is associated with intrathymic chimerism with MHC
      class II(IA+) cells, confluent in the medulla and scattered in the cortex. To
      clarify the anatomical site for the deletional signaling, we injected Mls-1a PerC
      cells directly into the thymus lobe of BALB/c mice on the day of birth. Thus
      induced tolerant state was limited to the injected lobe and there was no
      penetration to the contralateral lobe. The tolerant state lasted less than 2
      weeks, by which time donor-derived Ia+ cell had disappeared from the thymus.
      Thus, PerC cells seem to have little self-renewing ability. One week after the
      intrathymic injection of a small amount (0.3 microliter) of PerC cell suspension
      in several different sites, the thymus lobes were removed without killing the
      mice and serial cryostat sections were cut and stained immuno-histochemically for
      analysis of the donor cell distribution. Four weeks later, the functional
      activities of peripheral T cells in the spleens of the treated mice were tested.
      These experiments revealed that inoculated cells lodging in the medulla, but not
      in the cortex, induced tolerance to the Mls determinants. Target thymocytes for
      negative signaling are probably located in the medulla/juxta-medullary area in
      the thymus. Data are discussed in relation to Mls-bearing stroma cells in the
      thymus.

PMID- 1387745
TI  - Kinetics of clonal deletion varies with tolerizing antigen.
AB  - In postnatal AKR/J mice (I-Ek, Mls-1a) potentially autoreactive T-cells bearing V
      beta 11+ or V beta 6+ TcR are present until day 4, rapidly decreasing thereafter.
      Clonal deletion of V beta 11+ and V beta 6+ T-cells shows equivalent kinetics and
      is complete after day 7 to 8. Analysis of transgenic mice expressing a TcR with
      double specificity for LCMV/H-2Db and for Mls-1a revealed that in mice
      congenically infected with lymphocytic choriomeningitis virus (LCMV) T-cells
      bearing the transgenic TcR were already deleted at birth, whereas in uninfected
      TcR-transgenic Mls-1a mice deletion was delayed. These findings document that the
      capacity of the thymus to induce tolerance by clonal deletion is already
      established at birth and that the kinetics of clonal deletion varies with
      tolerizing antigen.

PMID- 1387746
TI  - [The effect of arginine on hydrolysis of fibrinogen by plasmin and mini-plasmin].
AB  - The rate of plasmin or Val442-plasmin catalyzed hydrolysis of fibrinogen
      decreases several times as affected by arginine in high concentrations. The
      enzyme is shown to be not inhibited by arginine. The observed effect is supposed
      to depend on saturation of the protein-proteins interaction sites located between
      442 and 790 amino acid residues.

PMID- 1387747
TI  - [The effect of osmotic pressure on oligomycin-sensitive ATPase activity and the
      liberation of Mg2+ from liver mitochondria of rats of various ages].
AB  - The influence of osmotic pressure of the incubating medium (25-500 mM sucrose) on
      oligomycin--sensitive, 2,4-dinitrophenyl-stimulated ATP-ase-activity, Mg2+
      release and swelling of the liver mitochondria in 1-, 3-, 12-, 24-months Wistar
      rats is, investigated to determine age changes of structurally functional state
      of mitochondria. An increase in the sucrose concentration in the medium from 150
      to 500 mM causes almost equal and practically absolute inhibition of ATP-ase
      activity in different-age groups of rats, regardless of the presence or absence
      of Mg2+ ions in the medium A fall of the sucrose concentration to 150-25 mM
      induces a decrease in mitochondria ATP-ase-activity in Mg2+ free medium in 12-
      and 24-months rats (to 30 and 22%, respectively). No changes are observed in 1-
      and 3-months animals. Differences in rates of exogenous NADH oxidation by
      mitochondria of 1- and 12-months rats as a reflection of inner membrane damage
      degree are not observed under these conditions. Relative changes in ATP-ase
      activity in a Mg2+ free medium with sucrose concentration of 25 mM (compared with
      150 mM) correlate (r = 0.82) with those of optical density of mitochondria,
      measured at light wave length of 520 nm. It is obvious that the liver
      mitochondria of young and old rats sufficiently differ in spontaneous swelling
      rate in the media with different osmotic pressure: mitochondria of 1-month rats
      swell much faster than those of old rats. Considerable age differences of osmotic
      dependence of Mg2+ output from mitochondria are observed. They depend also on
      peculiarities of spontaneous organelle swelling dynamics.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1387748
TI  - [Transport of Ca2+ in the sarcoplasmic reticulum of skeletal muscles in
      hyperthermia].
AB  - Study of functional changes in sarcoplasmic reticulum membranes of the rat
      skeletal muscles shows that mild hyperthermia is accompanied by the activation of
      Ca-transporting system function (the increase in accumulation of Ca ions and the
      rise of Ca(2+)-ATPase activity are observed), a passive release of this ion being
      unchanged. The revealed changes are regarded as reaction induced by the body
      temperature increase. The effectiveness of the SR Ca-pump decreases sharply under
      heat stroke, but the increase of Ca2+ release from SR vesicles is observed. This
      is considered to be one of possible factors, causing disorder of
      electromechanical coupling and the disturbance of the skeletal muscle
      contractility.

PMID- 1387749
TI  - Dugbe Nairovirus M RNA: nucleotide sequence and coding strategy.
AB  - The coding assignments of the medium-sized (M) RNA segment of the Dugbe (DUG)
      virus (Nairovirus, Bunyaviridae) were investigated. The complete nucleotide
      sequence of 4888 nucleotides (nt) contained one long open reading frame in the
      viral complementary RNA, extending from an AUG start codon at nt 48-50 to a stop
      codon at nt 4701-4703 (numbered from the 5' terminus of vcRNA). Comparison of the
      terminal sequences with the ends of the DUG S segment revealed sequence identity
      between the first nine nucleotides of both segments. No sequence homologies were
      found with the M segments of other members of the Bunyaviridae, or with their
      polypeptide products. Expression of portions of the DUG M open reading frame in
      Escherichia coli demonstrated the carboxyl terminal region of the M open reading
      frame codes for the G1 structural glycoprotein, which is the target for
      neutralising antibodies. Confirmation of this assignment was obtained by
      sequencing the amino terminus of the G1 protein. Two nonstructural glycoproteins
      which share epitopes with G1 were identified in virus-infected cells, one of
      which (85 kDa) is processed over a period of several hours to produce G1. The G2
      coding region was located upstream of the G1 sequence. The region between the
      carboxyl terminus of G2 and the 5' end of the long open reading frame apparently
      encodes a nonstructural protein of about 70 kDa, which is a precursor of the G2
      protein.

PMID- 1387750
TI  - Construction, characterization, and utilization of cell lines which inducibly
      express the adenovirus DNA-binding protein.
AB  - To further our understanding of structure-function relationships within the
      multifunctional adenovirus DNA binding protein (DBP) a more diverse collection of
      mutants is necessary. DBP-expressing cell lines (gmDBP) were previously
      constructed that complemented DBP-negative mutants for viral growth. However,
      they did not allow severely defective viruses to form plaques. Since efficient
      mutant construction is reliant on plaque isolation of the desired mutant virus as
      a final step, additional gmDBP cell lines were constructed which allow all DBP
      negative mutants to form plaques. Here we describe the construction and
      characterization of 12 new gmDBP cell lines. The utility of these lines was
      demonstrated by the efficient construction of a new defective mutant, H5in804,
      using a combination of DBP-expressing lines. The H5in804 mutation adds 22 amino
      acids at the carboxyl end of an otherwise wild type protein. Characterization of
      H5in804 revealed that it was altered in its ability to replicate viral DNA. The
      depression of DNA synthesis most probably results from a reduced ability of
      H5in804 DBP to bind ssDNA.

PMID- 1387752
TI  - Expression, purification, and functional characterization of adenovirus 5 and 12
      E1A proteins produced in insect cells.
AB  - The 12 S and 13 S E1A cDNAs from both the Adenovirus (Ad) nononcogenic type 5 and
      the oncogenic type 12 were overexpressed in an insect cell/baculovirus system.
      Upon infection of Spodoptera frugiperda cells, the production of E1A proteins
      reached a level of about 15 micrograms/10(6) cells. The E1A proteins are highly
      soluble and apparently are processed authentically. They are readily recognized
      by various antibodies and display phosphorylation patterns similar to those of
      E1A proteins synthesized in mammalian cells. Single-step immunoaffinity
      chromatography was used to purify the Ad5 E1A proteins to near homogeneity under
      nondenaturing conditions. The Ad5 and Ad12 E1A proteins are able to form
      complexes with the retinoblastoma susceptibility gene product (Rb) and other
      cellular proteins. Interestingly, the presence of a cellular extract seems to be
      a prerequisite for association between highly purified E1A and Rb polypeptides.

PMID- 1387751
TI  - Stimulation of adenovirus early gene expression by phorbol ester: its possible
      mechanism.
AB  - Treatment of Hela cells infected with adenovirus 5 wild type (Ad5WT) with the
      tumor-promoting phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate),
      accelerated as well as stimulated expression of viral early genes EII and EIII
      but not that of EIA. TPA treatment of HeLa cells infected with dl312, an Ad5 EIA
      deletion mutant, activated expression of EIII but not EII. Stimulation of EII and
      EIII expression was blocked by H7 (1-5-isoquinolinyl sulfonyl-2-methyl
      piperazine), a specific inhibitor of protein kinase c (PKc). Nuclear run off
      assays demonstrated that TPA exerted a stimulatory effect at the level of
      transcription. PKc inhibitor alone reduced transcription of early genes in the
      absence of TPA activation. Phosphorylation of EIA 35 kDa but not 40- to 45-kDa
      proteins was dramatically increased by TPA. Three cellular proteins of 200, 24,
      and 20 kDa which coprecipitated with EIA proteins underwent enhanced and
      preferential phosphorylation by activated PKc. Inhibitor of PKc blocked
      phosphorylation of cellular proteins and reduced phosphorylation of EIA 35 kDa
      but not EIA 40- to 45-kDa proteins. These results tend to indicate that TPA
      stimulates adenovirus early gene expression through activation of protein kinase
      c and further suggest but do not prove that this may be due to specific
      phosphorylation of EIA 35 kDa and cellular proteins of 200, 24, and 20 kDa.

PMID- 1387753
TI  - The BPV-1 E5 oncoprotein expressed in Schizosaccharomyces pombe exhibits normal
      biochemical properties and binds to the endogenous 16-kDa component of the
      vacuolar proton-ATPase.
AB  - The 44-amino-acid E5 oncoprotein of bovine papillomavirus type 1 transforms
      immortalized murine fibroblast cell lines. This highly hydrophobic protein forms
      homodimers, localizes to intracellular membrane compartments (including the Golgi
      apparatus), and forms a complex with the 16-kDa membrane-embedded constituent
      (16k) of the vacuolar proton-ATPase. To develop a system for the genetic and
      biochemical analysis of the E5/16k interaction, the E5 gene was cloned into a new
      vector which was designed for expression in the fission yeast Schizosaccharomyces
      pombe. The E5 protein synthesized in this system dimerized normally and bound to
      endogenous and overexpressed S. pombe 16k protein. Comparison of the S. pombe and
      mammalian 16k proteins showed strong conservation in carboxyl-terminal amino
      acids but greater variation in the amino-terminal sequences, suggesting that E5
      was interacting with the 16k carboxyl domains. Finally, a new protein epitope tag
      is described which permitted for the first time the coprecipitation of E5 with
      antibodies directed against the 16k protein.

PMID- 1387754
TI  - Comparative virulence of NAD-dependent and NAD-independent Actinobacillus
      pleuropneumoniae strains.
AB  - The virulence of a NAD-independent Actinobacillus pleuropneumoniae serotype 2
      strain and NAD-dependent serotype 2, 3 and 9 strains was compared under
      experimental conditions. Hysterectomy-derived piglets were inoculated
      endobronchially with 50-500 cfu of these strains. All 23 piglets inoculated with
      the NAD-dependent strains developed acute disease within 12 hours post
      inoculation. Twenty-two of these piglets died within 24 hours after the first
      clinical signs. Three of nine piglets inoculated with the NAD-independent strain
      did not develop clinical disease. In the other six piglets, disease signs were
      similar as in the piglets inoculated with the NAD-dependent strains. No
      differences in clinical disease were observed between colostrum deprived piglets
      and piglets that obtained colostrum from a SPF sow.

PMID- 1387755
TI  - Thyroid hormones and atrial natriuretic hormone secretion: study in hyper- and
      hypothyroid patients.
AB  - Plasma atrial natriuretic hormone (ANH) values were evaluated in 28 hyperthyroid
      patients and in 11 hypothyroid patients and compared with 20 healthy subjects. In
      hyperthyroid patients plasma ANH basal levels were significantly (p less than
      0.01) higher (14.2 +/- 1.6 pmol/l) than in controls (7.8 +/- 0.4 pmol/l) and in
      hypothyroid patients (6.4 +/- 0.3 pmol/l). No significant differences were found
      between controls and hypothyroid patients. The propranolol-induced decrease in
      heart rate in hyperthyroid patients did not significantly affect the plasma ANH
      values. Conversely, after the methimazole-induced euthyroidism a return within
      the normal range of ANH values was observed. The thyroxine replacement in
      hypothyroid patients determined a small but significant (p less than 0.05)
      increase in plasma ANH values. Observed data suggest that in humans thyroid
      hormones may influence plasma ANH concentrations independently of their effect on
      heart rate.

PMID- 1387756
TI  - Effect of pancreas transplantation on decreased levels of circulating bone gamma
      carboxyglutamic acid-containing protein and osteopenia in rats with
      streptozotocin-induced diabetes.
AB  - Diabetic osteopenia has been known as one of the chronic complications of
      diabetes mellitus, and a decrease in bone turnover has been thought to be one of
      the pathophysiological characteristics of this complication. In order to
      investigate the effect of long-term insulin therapy on low bone turnover in
      diabetes, pancreas transplantation was performed on streptozotocin-induced
      diabetic rats. Plasma levels of bone gamma-carboxyglutamic acid-containing
      protein(osteocalcin) in untreated diabetic rats were 0.9 +/- 0.1 (mean +/- SEM)
      nmol/l, significantly lower than the value of 4.2 +/- 0.6 nmol/l in control rats
      (p less than 0.01). Pancreas transplantation reversed this decrease to 6.3 +/-
      1.1 nmol/l, which was not significantly different from the value in control rats.
      The circulating levels of calcitriol were significantly decreased in the
      untreated diabetic group (p less than 0.01), and the decrease was fully reversed
      by pancreas transplantation. In addition, the decreases in bone length, strength
      and weight were also improved by the transplantation. This evidence clearly shows
      that the improvement of metabolic derangements in diabetes by insulin is
      essential for the prevention of deterioration in diabetic osteopenia. It is
      possible, therefore, that insulin exerts an indirect beneficial influence through
      the metabolic amelioration on the decreases in bone turnover and circulating
      osteocalcin in diabetes mellitus, or has a direct stimulatory effect on the
      osteoblasts via the insulin receptor since its presence has been shown recently
      in osteoblastic cells.

PMID- 1387757
TI  - Platelet-specific proteins in myeloproliferative disorders.

PMID- 1387758
TI  - Beta thromboglobulin and increased platelet activation after streptokinase
      treatment of acute myocardial infarction.

PMID- 1387759
TI  - An unusual complication of paracentesis.
AB  - Paracentesis is an important and commonly performed procedure in patients with
      ascites. It is a safe procedure when carried out in the midline below the
      umbilicus, with a complication rate of less than 1%. We report an instance in
      which a large midline varix was entered during paracentesis. The utility of
      different imaging techniques in detecting such anomalies in the portal
      hypertensive patient with portal hypertension and ascites is discussed. The
      approach and management of this complication are outlined.

PMID- 1387760
TI  - Use of provincial health insurance plan billing data to estimate carpal tunnel
      syndrome morbidity and surgery rates.
AB  - Following a work refusal at a plant manufacturing ice cream novelties in Ontario,
      we were asked to document cases of cumulative trauma disorders (CTDs) and carpal
      tunnel syndrome (CTS) in this workplace. There were 17 employees with possible
      hand and wrist problems identified from Workers Compensation Board (WCB) Forms,
      and from a list prepared at the time of the refusal. After obtaining consents,
      confirmations of the diagnoses of CTDs, CTS, and of surgical procedures for CTS
      were obtained from the physicians involved. The relative risk for these disorders
      among plant employees was estimated in two ways: 1) the rate of CTS operations
      between 1979 and 1990 was compared to that in the general population using
      Ontario Health Insurance Plan (OHIP) data on physicians' billings for these
      operations; and 2) the frequency of WCB first payment claims for tendinitis and
      CTS during 1987 to 1989 at the plant was compared to that among the entire labor
      force of Ontario. CTDs had been diagnosed in all 17 workers: 9 had had operations
      for CTS, but one had had this operation prior to working at the plant. Compared
      to the remaining 8 workers who had CTS operations, an estimated 0.08 CTS
      operations would be expected among the 150 employees on the plant's seniority
      lists between 1979 and 1990, if the estimated rates in the general population
      were present at the plant, giving a Standardized Morbidity Ratio of 10.0 (95%
      confidence interval [CI] 4.3-19.7; one-sided p = 2.1 x 10(-6)). There were 6 WCB
      claims for tendinitis and CTS among plant employees during 1987 through 1989.
      This frequency was about 68 times that in the entire Ontario labor force (95% CI
      24.7-150). This investigation has shown that CTDs, and particularly CTS,
      documented by medical records, have occurred at least 10 times more frequently
      than expected at this plant. Use of health insurance billing data to estimate CTS
      operation rates represents a simple method for estimating the burden of illness
      at the individual plant level due to CTS (at least for that portion proceeding to
      surgery), using an objective outcome that can be confirmed from medical records.

PMID- 1387761
TI  - Attitudes about asbestos and lung cancer.

PMID- 1387763
TI  - Hypertension, left ventricular hypertrophy, ventricular ectopy, and sudden death.
AB  - Left ventricular hypertrophy (LVH) is a common sequela of sustained arterial
      hypertension, although the correlation between spot blood pressure measurements
      and LV mass is not a close one. LVH has been shown to be a powerful blood
      pressure-independent risk factor for cardiovascular morbidity and mortality. LVH
      has been shown to trigger or to accelerate ventricular dysrhythmias, although the
      connection between ventricular dysrhythmias and sudden death is poorly
      documented. LVH can be reduced by specific antihypertensive therapy; however, not
      all drugs are equipotent in this regard. A reduction of LVH has been shown to be
      associated with a suppression of ventricular dysrythmias. Preliminary studies
      also indicate that the reduction of LVH may reduce its inherent excessive
      morbidity and mortality.

PMID- 1387762
TI  - Cellular calcium and magnesium metabolism in the pathophysiology and treatment of
      hypertension and related metabolic disorders.
AB  - We have investigated the cellular basis for the clinical and epidemiologic
      linkage of hypertension, left ventricular hypertrophy (LVH), obesity, and non
      insulin-dependent diabetes mellitus (NIDDM) and have studied cytosolic free
      calcium and free magnesium levels in these syndromes. Specifically, intracellular
      free calcium is elevated and free magnesium is deficient in hypertension, and
      both are related (directly and inversely, respectively) to the ambient level of
      blood pressure, to LV mass index (and thus to the degree of cardiac hypertrophy),
      and to the hyperinsulinemia and insulin resistance of essential hypertension.
      Dynamically, the ability of dietary salt loading to elevate blood pressure
      corresponds to its ability to elevate cytosolic free calcium and reciprocally to
      suppress free magnesium levels. Conversely, the ability of calcium channel
      blockade to reverse salt-induced hypertension is related to its ability to
      prevent these transmembrane ionic effects. Higher steady-state free calcium or
      lower free magnesium, or both, are also observed in clinical states linked to
      hypertension, such as obesity and NIDDM. Oral glucose loading in normal subjects
      itself elevates free calcium and suppresses free magnesium levels, as does
      hyperglycemia in vitro. These data suggest an ionic hypothesis of cardiovascular
      and metabolic disease, in which a generalized defect in cell ion handling is
      present in all tissues, resulting in higher steady-state free calcium and lower
      free magnesium levels. In pancreatic beta cells, this would produce
      hyperinsulinemia; in fat and skeletal muscle, cause peripheral insulin
      resistance; and in renal tissue, increase proximal sodium resorption and increase
      urinary calcium excretion--all features of essential hypertension. In vascular
      smooth muscle, high cytosolic free calcium would increase smooth muscle tone and
      cause vasoconstriction, and in heart muscle, independent of blood pressure, would
      increase contractility and predispose to LVH. Therefore, what may appear
      clinically to be the separate syndromes of hypertension, obesity, and NIDDM may
      pathophysiologically be different manifestations of the same underlying cellular
      defect, thus explaining their frequent clinical coexistence. Therapeutically,
      reversal of this excess free calcium accumulation and/or free magnesium deficit
      with ion-specific agents, such as calcium channel blocking drugs, may thus
      ameliorate not only the elevated blood pressure of hypertension but also the
      concurrent excess morbidity and mortality of the concurrent cardiac, vascular,
      and metabolic aspects of the hypertensive state.

PMID- 1387764
TI  - DNA-testing for Huntington's disease in The Netherlands: a retrospective study on
      psychosocial effects.
AB  - Presymptomatic DNA-testing for Huntington's disease has made it possible to
      predict whether or not at-risk individuals are gene-carriers with a reliability
      of about 98%. In our retrospective study of 18 tested individuals, most of the
      newly identified carriers function apparently well. They use avoidance and
      repression of affect as psychological defense strategies. However, 8 out of 9 non
      carriers do not experience the expected relief about their test results. They
      experience survivor guilt and emotional numbness and find it difficult to cope
      with the effects of the test results on the family system. The partners of gene
      carriers are at risk of becoming emotionally isolated by putting aside their own
      feelings for fear of seeming self-centered. Appreciation of these effects on
      tested individuals is important and professional support is needed to prevent
      post-traumatic stress disorders. Whatever the test result may be, the working
      through process may take years rather than months. These findings have important
      implications for patient care and necessitate an extended period of observation
      after presymptomatic testing.

PMID- 1387765
TI  - Mivacurium chloride: a study to evaluate its use during propofol-nitrous oxide
      anaesthesia.
AB  - We assessed the neuromuscular and cardiovascular effects of mivacurium chloride,
      a neuromuscular blocking agent, in 33 patients during propofol-nitrous oxide
      anaesthesia. Neuromuscular function was assessed with supramaximal stimuli of the
      ulnar nerve, using surface electrodes at the wrist, with repeat trains of four.
      Mivacurium given as a bolus of 0.15 mg.kg-1 (ED95 x 2) was found to be
      haemodynamically stable. Intubating conditions assessed at 2 and 2.5 min were
      either good or excellent. All patients developed a block of 100% in a mean (SD)
      time of 105 (34) s. There were mean (SD) intervals of 12 (2.4) min before the
      reappearance of the first twitch of the train of four (T1) following the bolus
      dose, and 15.8 (3.1) min for the T1 to reach 25% of its control value (TC).
      Seventeen patients received an infusion of mivacurium to maintain neuromuscular
      blockade (T1:TC 10-20%) with a mean (SD) infusion rate of 6.9 (2.2) micrograms.kg
      1.min-1. Recovery from neuromuscular blockade was assessed with spontaneous
      offset or augmented with edrophonium following either the initial bolus or an
      infusion. Following a bolus it took a mean (SD) of 26.2 (3.7) min for the fourth
      twitch of the train of four (T4):T1 ratio to reach 0.7. In patients receiving an
      infusion with spontaneous offset it took a mean (SD) time of 12.0 (2.2) min to
      reach the T4:T1 ratio of 0.7 from a T1:TC value of 8.8. Edrophonium significantly
      decreased the recovery time in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387766
TI  - Sexual differentiation and the germ cell in sex reversed gonads after aromatase
      inhibition in the chicken embryo.
AB  - Chicken embryos were treated on day three of incubation with a steroidal or a non
      steroidal aromatase inhibitor (1-methyl-androstendion, CGS 16949 A). Complete sex
      reversal of ovaries into testes or intermediate stages of sex reversal resulted
      from the inhibitory effect on oestradiol formation during gonadal development
      before and during sexual differentiation. Germ cell differentiation shifted from
      the female to the male pattern depending on the local advance of sex reversal.

PMID- 1387767
TI  - Ondansetron does not affect alfentanil-induced ventilatory depression or
      sedation.
AB  - Ondansetron is a selective 5-hydroxytryptamine type 3 receptor antagonist
      effective as an antiemetic in patients experiencing post-operative or cancer
      chemotherapy-induced nausea and vomiting. Currently, no information is available
      regarding the interaction of ondansetron with opioids, although a serotonin
      antagonist might be expected to modify some opioid actions. This study was
      designed to measure the effects of ondansetron on alfentanil-induced ventilatory
      depression and sedation in healthy male volunteers. Ventilatory drive (measured
      as the end-tidal CO2 necessary to produce a minute ventilation of 15 l/min) was
      determined in 29 subjects using a modification of the Read rebreathing technique.
      Sedation was measured by asking the subjects to complete visual analog scales.
      Alfentanil was administered as a bolus (5 micrograms/kg) followed by a continuous
      infusion (0.25-0.75 micrograms.kg-1.min-1) for at least 90 min. Study medication
      (ondansetron 8 or 16 mg or vehicle placebo) was then administered in a
      randomized, double-blind manner, and the alfentanil was infused for an additional
      15 min. Measurements of ventilatory drive and sedation were made at baseline,
      during alfentanil infusion, after study medication, and at 30-min intervals after
      alfentanil was discontinued. Alfentanil produced significant ventilatory
      depression (P less than 0.001) and sedation (P less than 0.001) in all three
      groups. Neither placebo nor ondansetron produced further change in the intensity
      of either alfentanil effect. After discontinuation of the opioid, both
      ventilatory depression and sedation decreased, and the rate of recovery was not
      significantly different between groups. The data indicate that alfentanil-induced
      sedation and ventilatory depression are not significantly affected by the
      subsequent administration of ondansetron.

PMID- 1387768
TI  - Left ventricular hypertrophy in rabbits does not exaggerate the effects of
      halothane on the intracellular components of cardiac contraction.
AB  - Inhalational anesthetics and ventricular hypertrophy have adverse effects on
      cardiac muscle contraction. The effects of 1, 2, and 3% halothane on the
      contractile protein and sarcoplasmic reticulum, but not the sarcolemma, were
      examined in normal left ventricular tissue from rabbits that underwent a sham
      surgical procedure (n = 5) and in left ventricular hypertrophied tissue from
      surgically induced aortic coarctation (n = 7). Muscle samples were mechanically
      "skinned" to disrupt the sarcolemma. Fiber bundles were mounted in photodiode
      transducers and bathed in a series of solutions designed to examine the
      contractile protein [Ca2+]-tension responses or to examine Ca2+ storage by and
      release from the sarcoplasmic reticulum. Hill equation analysis of the [Ca2+]
      tension relationship of the contractile protein was performed. Compared to normal
      muscle, hypertrophied muscle was associated with an 8.2% decrease in the [Ca2+]
      necessary for 50% maximum tension (more sensitive to Ca2+) (P less than 0.001)
      and an increase in the slope constant of 23% (P less than 0.001). In normal and
      hypertrophied tissue, each 1% of halothane incrementally decreased the
      contractile protein response to maximal [Ca2+] by 5% (P less than 0.01),
      increased the [Ca2+] at 50% maximum tension by 5% (P less than 0.01), and had no
      effect on the slope of the Hill equation. Halothane also inhibited Ca2+ storage
      by the sarcoplasmic reticulum. In normal muscle, 1, 2, and 3% halothane decreased
      the stored Ca2+ to 42, 22, and 9%, respectively, of Ca2+ storage without
      halothane (P less than 0.001). However, hypertrophied muscle demonstrated
      slightly less depression (P less than 0.05 by analysis of variance).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1387769
TI  - Spinal toxicity after repeated intrathecal sufentanil administrations in sheep.

PMID- 1387770
TI  - Score: hepatitis viruses 5, vaccines 1. Researchers believe sixth virus exists.

PMID- 1387771
TI  - Recent laws affect HIV-infected workers.

PMID- 1387772
TI  - Acute bronchodilator trials in chronic obstructive pulmonary disease.
AB  - Short-term trials of bronchodilator drugs are widely used to assess patients with
      stable chronic obstructive pulmonary disease (COPD), but there is an uncertainty
      about the equivalence of the FEV1 response to beta-agonists and anticholinergic
      drugs, their relative ability to identify patients likely to improve with
      corticosteroids, the most appropriate way to express the results of these tests,
      and whether age or allergic status affects the beta-agonist and anticholinergic
      response differently. We studied 100 consecutive patients with stable COPD (mean
      FEV1, 0.96 +/- 0.48 L; mean age, 62 +/- 8 yr). Spirometry was measured before and
      after either 5 mg of nebulized salbutamol or 500 micrograms of nebulized
      ipratropium bromide and repeated after 2 wk of 30 mg of oral prednisolone daily.
      Total IgE, specific RAST, and skin prick testing values were recorded. Using
      modified American Thoracic Society response criteria, 33 patients failed to
      bronchodilate after the acute trials, 16 responded only to nebulized salbutamol,
      17 to nebulized ipratropium, and 34 to both drugs. Twenty-two patients improved
      after corticosteroids. This was usually detected by a positive acute trial
      response (salbutamol 90% specific; ipratropium 84% specific). Baseline FEV1
      differed between days, and in those who responded on only 1 day, this variation
      correlating with the response to ipratropium (r = 0.66). Expressing the response
      criterion as a percentage change in the available bronchodilatation increased the
      numbers responding with a high baseline FEV1, and vice versa. Neither age nor
      allergic status was related to the change in FEV1 after either drug in these
      patients. In COPD patients, testing with high-dose nebulized bronchodilators
      identifies a substantial number of partially reversible patients whatever age it
      is employed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387773
TI  - [Pharmacokinetic studies of menogaril (TUT-7) with rats].
AB  - Menogaril (TUT-7) is a novel antitumor antibiotic belonging to anthracyclines.
      The pharmacokinetic parameters derived from plasma concentration-time profiles
      after repeated (for 14 days) or single oral administration of TUT-7 to rats were
      found to be not significantly different by either administration schedule. The
      rats with artificial liver dysfunction were obtained by subcutaneous application
      of carbon tetrachloride (CCl4, 1 ml/kg) for 3 days. After oral administration of
      TUT-7 to the rats with CCl4-induced liver toxicity (3 daily administrations of
      1mg/kg, S.C.), the maximum plasma concentrations (Cmax) and AUC of both the
      unchanged drug and its metabolite N-Demethyl menogaril, were increased. Also over
      all elimination was slower in animals with liver dysfunction.

PMID- 1387774
TI  - [Investigation of anti-emetic effect of ondansetron tablet in multiple doses on
      nausea and emesis associated with cisplatin].
AB  - The anti-emetic effects, safety and usefulness of ondansetron, a 5-HT3 receptor
      antagonist, given orally once daily for 3-5 consecutive days, were investigated
      in patients receiving a high single dose (greater than or equal to 50 mg/m2 or 75
      mg/body) or lower multiple doses (greater than or equal to 15-20 mg/m2/day for 3
      5 consecutive days) of cisplatin. Ondansetron 4 mg was administered orally once
      daily for 3-5 consecutive days. Efficacy rates in controlling nausea and emesis
      over the 3-5 days were 77.3% (17/22 cases) and 66.7% (6/9 cases) in patients
      receiving a high single dose and lower multiple doses of cisplatin, respectively.
      Side effects were observed in 2 cases (headache and elevation of blood pressure
      in one case and only headache in the other case.). Abnormality in clinical
      laboratory findings was observed in 1 case. From the above, ondansetron, showing
      high efficacy by oral administration 4 mg once daily for 3-5 consecutive days,
      without any problem in safety, was considered to be a useful anti-emetic agent.

PMID- 1387775
TI  - [Examination of inhibitory effect, safety and usefulness of SN-307 (ondansetron)
      administered orally once daily for 3-5 consecutive days on nausea and emesis
      associated with non-platinum anti-cancer drugs].
AB  - We examined the anti-emetic effect, safety and usefulness of ondansetron
      hydrochloride, a selective 5-HT3 receptor antagonist, given orally once daily at
      the dosage of 4 mg, for 3 to 5 consecutive days to patients with nausea and
      emesis induced by non-platinum anti-cancer drugs such as cyclophosphamide,
      doxorubicin and carboplatin. Out of 84 cases where anti-emetic effects were
      evaluated, numbers of cases assessed as excellent and good were 36 (83.3%) and 34
      (40.5%), respectively, the efficacy rate being 83.3% (70/84). Side effects, such
      as moderate constipation (3 cases) and mild headache (3 cases), were observed in
      8/85 cases (9.4%). Abnormalities in clinical laboratory findings including
      elevation of hepatic function and uricacid values and increase in eosinocyte
      counts, were observed in 3/85 cases (3.5%). As to overall safety, 78/85 cases
      (91.8%) were evaluated as having no problem in safety, and 7/85 cases (8.2%), as
      having minor problem in safety. As to clinical usefulness based on anti-emetic
      effect and overall safety, out of 79 cases the drug was assessed as very useful
      in 29 cases (36.7%) and useful in 35 cases (44.3%), the rate of "useful" or above
      being 81.0% (64/79). Furthermore, when ondansetron was administered in 3 courses
      of chemotherapy, though the number of patients was small, it was shown that anti
      emetic effect of ondansetron did not decline and no problem in safety was
      observed. From the above, ondansetron which exerted adequate anti-emetic effect
      in 4 mg once daily doses was considered as a useful and safe anti-emetic in
      treatment of nausea and emesis associated with cancer chemotherapy.

PMID- 1387776
TI  - [Evaluation of SN-307 (ondansetron), given intravenously for the treatment of
      nausea and vomiting caused by anticancer drugs including cisplatin-open study].
AB  - The anti-emetic effect, safety and clinical usefulness of ondansetron for the
      treatment of nausea and vomiting caused by anticancer drugs including cisplatin,
      was evaluated by a multi-institutional study in patients with various
      malignancies. In this study, ondansetron was given intravenously with mainly a
      single dose of 4 mg to intervene nausea and vomiting. 1. Efficacy ratio of
      overall effects on nausea and emesis observed for 24 hours after treatment was
      69.8%. 2. No side effect was observed. Laboratory tests showed temporary
      elevation of serum uric acid level in 1 patient in the group given 4 mg. 3. From
      these results, it seems that ondansetron, given intravenously after initial
      vomiting, was highly safe and clinically useful anti-emetic for the treatment of
      nausea and vomiting associated with anti-cancer drugs.

PMID- 1387777
TI  - [A case of inflammatory breast cancer treated with medroxyprogesterone acetate
      (MPA) in combination with intra-arterial infusion chemotherapy].
AB  - A 55-year-old female with severe inflammatory breast cancer was treated with the
      combined use of MPA and the intraarterial infusion chemotherapy. One cycle
      consisted of 4'-epi-adriamycin; 210 mg (day 1, 4 and 8) and daily administration
      of MPA; 1,200 mg. A marked shrinkage of the tumor was obtained with this
      treatment. The regressive change was noted not only in the primary lesion but in
      lymph nodes of the axillary region. Therefore, the combined use of MPA with intra
      arterial infusion chemotherapy may well contribute to the treatment of
      inflammatory breast cancer.

PMID- 1387778
TI  - Inocoterone and acne. The effect of a topical antiandrogen: results of a
      multicenter clinical trial.
AB  - BACKGROUND AND METHODS: Because acne is androgen dependent, antiandrogen therapy
      might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal
      antiandrogen that binds to the androgen receptor and has antiandrogenic activity
      in animal models. To test its topical effect on acne, 126 male subjects with
      facial acne completed a 16-week, multi-center, double-blind study in which the
      twice-daily application of a 10% solution of inocoterone was compared with
      vehicle solution. Baseline and monthly examinations included acne lesion counts
      and general and endocrine laboratory tests. RESULTS: Inflammatory papules and
      pustules showed greater reduction in the inocoterone-treated subjects than in the
      subjects treated with vehicle. This difference achieved statistical significance
      by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with
      longitudinal analysis, throughout the course of the study. Global assessments and
      changes in comedo counts and sebum excretion rates were not significantly
      different between the groups. No serious adverse reactions were encountered.
      CONCLUSIONS: In this double-blind study of 126 male subjects with acne, a topical
      solution of the antiandrogen inocoterone, compared with vehicle, produced a
      modest but statistically significant reduction in the number of inflammatory acne
      lesions.

PMID- 1387779
TI  - Antiandrogens and acne. A topical approach?

PMID- 1387780
TI  - Coffee and coronary heart disease.
AB  - OBJECTIVE: We determined if coffee consumption is associated with an increased
      risk of developing coronary heart disease. DATA IDENTIFICATION: Articles
      published between 1966 and August 1991 examining a possible link between coffee
      and coronary heart disease were identified by a computer-aided literature search
      (Medline) and by standard bibliographic searches. STUDY SELECTION: All
      prospective cohort studies providing data on daily coffee consumption and
      coronary events (acute myocardial infarction and/or coronary death) were
      included. DATA EXTRACTION: Data from each published article were extracted.
      Additional unpublished data augmenting those published for one study were also
      included. Each cohort was categorized by reported daily coffee consumption.
      Incidence of coronary events at each level of coffee consumption was the primary
      outcome. RESULTS: Eleven prospective studies were included. The coronary events
      for subjects consuming little or no coffee (less than or equal to 1 cup per day)
      were compared with event rates for those consuming greater amounts of coffee. The
      studies exhibited heterogeneity of results. The typical odds ratios and 95%
      confidence intervals across studies were estimated by logistic regression
      analysis. Coffee intake from 1 to 4 cups per day was not associated with any
      increase in coronary heart disease occurrence compared with 1 cup or less per day
      (odds ratio, 1.01; confidence interval [0.93, 1.11]). The odds ratios for 4 to 6
      and 6 cups or more per day compared with up to 1 cup per day were 1.01 (0.90,
      1.12) and 1.09 (0.97, 1.22), respectively. CONCLUSIONS: There is no association
      between coffee consumption and the occurrence of coronary heart disease. This
      conclusion holds in the absence of adjustment for other coronary risk factors.

PMID- 1387781
TI  - The diagnosis of disability. Treating and rating disability in a pain clinic.
AB  - Medical diagnosis sanctions illness and directs physicians toward effective
      treatment. In chronic illness, these two functions of diagnosis can come into
      conflict. Nowhere is this conflict more striking than in the case of disability
      ratings for those with chronic pain. An institutional case study examining the
      relation between a pain clinic and a worker's compensation program is presented
      and analyzed in terms of two questions: (1) Is it ethical for one physician to
      both treat pain and rate disability in patients with chronic pain? (2) Is
      physician rating of disability due to pain scientifically valid? Ethical and
      conceptual analyses support a negative response to each of these questions. The
      roots of the ethical and scientific problems concerning disability ratings are
      identified in society's demand to differentiate medical and nonmedical distress.
      We propose a system of time-limited compensation for pain as a therapeutically
      superior alternative to disability ratings.

PMID- 1387782
TI  - Clinical relevance of nighttime blood pressure and of daytime blood pressure
      variability.
AB  - BACKGROUND: The purpose of this study was to assess whether hypertensive target
      organ damage is related to average nighttime blood pressure (BP) and to BP
      variability. METHODS: Sixty-seven normotensive subjects and 171 borderline, 309
      mild, 140 moderate, and 41 severe hypertensive patients were studied with
      noninvasive ambulatory BP monitoring. Each subject was assigned a target organ
      damage score of 0 to 5 on the basis of funduscopic changes and degree of left
      ventricular hypertrophy calculated from electrocardiogram and chest
      roentgenogram. RESULTS: When the 728 subjects were subdivided into five classes
      of increasing daytime BP, in each class a significantly higher degree of target
      organ damage was present in the subjects with higher nighttime diastolic BP. A
      similar, although nonsignificant, trend was observed in the subjects with higher
      nighttime systolic BP. In particular, higher nighttime BP levels were accompanied
      by a more severe degree of left ventricular hypertrophy. As for variability,
      subjects with higher daytime systolic BP SD, but not with higher daytime
      diastolic SD, displayed a more severe degree of target organ damage; this was
      accounted for by a higher degree of retinal abnormalities. The association
      between target organ damage and systolic BP SD was present both in men and women,
      while that with nighttime BP was present only in men. No relationship was found
      between degree of cardiovascular complications and peaks of pressure.
      CONCLUSIONS: These results suggest that a reduced day-night BP difference and an
      increased daytime BP variability, evaluated as the SD, are associated with a
      higher degree of hypertensive cardiovascular complications. Whether this BP
      profile is the cause or the consequence of target organ damage remains to be
      established.

PMID- 1387783
TI  - Non-innervated Merkel cells and Merkel-neurite complexes in human oral mucosa
      revealed using antiserum to protein gene product 9.5.
AB  - Merkel cells are non-keratinized cells present in many different epithelia, but
      whose origin and functional role are still controversial. They were here
      investigated by means of antisera to the neural and neuroendocrine markers
      protein gene product 9.5 (PGP 9.5), and neurone-specific enolase. The expression
      of both markers in Merkel cells of human gingival and palatal mucosa was
      confirmed. Merkel cell-neurite complexes and isolated non-innervated Merkel cells
      had a similar morphology when stained by either antiserum. Merkel-neurite
      complexes were clustered in relatively large numbers in the lingual gingiva, thus
      constituting structures closely similar to the 'touch domes' in the skin.
      Clusters of non-innervated cells showing the same immunohistochemical features as
      Merkel cells were also demonstrated. In other areas of the oral mucosa, the
      innervated and non-innervated elements were only occasionally seen but there were
      many encapsulated Meissner-like receptors. When comparing the two different
      antisera, anti-PGP 9.5 appeared to provide a more consistent labelling of small
      fibres inside the epithelium and of bulb-like terminals on Merkel cells.

PMID- 1387784
TI  - General surgery and the laparoscope.

PMID- 1387785
TI  - Scissor dissection technique for laparoscopic cholecystectomy: an alternative to
      laser and electrocautery.
AB  - A sharp dissection technique, using specially designed curved insulated scissors,
      is described for use in laparoscopic cholecystectomy. This technique is a
      suitable alternative to laser and electrocautery, and produced a significant
      shortening of operating time.

PMID- 1387786
TI  - Diagnosis and surgical management of endometriomas.
AB  - Fifty two patients with endometriomas greater than 1 cm were treated by surgical
      excision either with or without ovarian closure. Diagnosis is reliable when
      clinical features of the pain, vaginal ultrasound, and laparoscopy, including
      ovarian mobilization and needling, are considered. Fifty of 52 patients were free
      of pain after 1 year and 26 (50%) became pregnant within 1 year. A second
      laparoscopy is justified if pain persists or pregnancy does not occur. Adhesive
      disease was the most common complication (40%), and persistent or recurrent
      endometriosis occurred in 15%. Surgery by laparoscopy with drainage and excision
      of the endometrioma without ovarian sutures may be more effective than excision
      of the endometrioma and ovarian suture.

PMID- 1387787
TI  - Human platelets express the SERCA2-b isoform of Ca(2+)-transport ATPase.
AB  - Previous biochemical studies suggested that the human platelet Ca2+ATPase system
      may be cell-specific. To test this hypothesis, we first undertook the molecular
      cloning of Ca2+ATPase from human erythroleukaemia (HEL) cells, because this human
      cell line exhibits megakaryocytic features and expresses a Ca2+ATPase that cross
      reacts with platelet Ca(2+)-ATPase. For this cloning, an HEL-cell cDNA library
      was screened with a rat cardiac Ca2+ATPase cDNA probe. The insert of the longest
      clone isolated was 3.9 kb and its sequence displayed a 100% identity with that of
      the non-muscle human Ca2+ATPase 2-b isoform, termed SERCA2-b (sarco-endoplasmic
      reticulum Ca2+ATPase). The 3.9 kb cDNA covered a subtotal coding region and part
      of the 3' non-coding end of the SERCA2-b mRNA. It cross-hybridized with the 4 kb
      transcript species of cardiac SERCA2-a and with non-muscle SERCA2-b mRNAs, but
      not with fast-skeletal-muscle SERCA1 mRNA. We next confirmed that SERCA2-b was a
      component of the platelet Ca2+ATPase system because (1) the platelet clones
      isolated from a platelet cDNA library exhibited a 100% homology with HEL-cell
      cDNA; (2) SERCA2-b mRNA was amplified by PCR on total platelet RNA and (3)
      platelet Ca2+ATPase cross-reacted with a polyclonal SERCA2-b-specific antiserum.
      Platelets therefore contain a Ca2+ATPase definitely identified as the SERCA2-b
      isoform of Ca2+ATPase, thus eliminating the possibility that they only contain a
      single specific Ca2+ATPase.

PMID- 1387789
TI  - Isolation of human retinal genes: recoverin cDNA and gene.
AB  - A human retina cDNA library enriched for retina-specific clones was prepared by
      subtraction with a non-retina population of cDNA in combination with polymerase
      chain reaction (PCR) amplifications. A highly retina-specific cDNA clone (1190
      bp) was obtained through this library encoding a 200 amino acid protein with
      three calcium binding sites and 87% homology to the bovine photoreceptor protein,
      recoverin, which has been shown to mediate the recovery of the dark current after
      photoactivation, and 58% homology to the calcium-binding chick cone protein,
      visinin. Analysis of the gene indicated a 9-10 kb single-copy gene with at least
      three exons and two introns. The three exons contained the entire coding
      sequence, and all of the calcium-binding EF-hand regions were in putative exon 1.
      The recoverin gene was mapped to human chromosome 17 by hybridization to a panel
      of human-rodent hybrid DNAs.

PMID- 1387788
TI  - A large decrease in heat-shock-induced proteolysis after tryptophan starvation
      leads to increased expression of phage lambda lysozyme cloned in Escherichia
      coli.
AB  - The R gene coding for phage lambda lysozyme (lambda L), cloned under the control
      of the PL promoter on a multicopy vector, is expressed in an Escherichia coli
      strain auxotrophic for tryptophan. Induction by a thermal shift after tryptophan
      supplementation in a culture initially brought into stationary phase by
      tryptophan starvation leads to highly increased expression. A thermally unstable
      mutant protein, difficult to obtain under standard conditions, can be easily
      produced by post-stationary-phase expression. It is shown that this is due to a
      drastic decrease in the heat-shock-induced proteolysis normally observed on
      thermal induction. These data are discussed in relation to our present knowledge
      of stringent and heat-shock responses.

PMID- 1387790
TI  - The same chemicals induce different neurotoxicity when administered in high doses
      for short term or low doses for long term to rats and dogs.
AB  - Dose- and term-dependent differences in the location and nature of brain lesions
      induced in rats and dogs by 2,5-hexanedione (2,5-HD), misonidazole, clioquinol,
      and acrylamide are reported. Subchronic neuropathies ("distal axonopathy") were
      induced by low-dose administration of these neurotoxicants and at high doses,
      lesions caused by acute or subacute neurotoxicity were found in the central
      nervous system (CNS). In rats, 2,5-HD induced extracellular edema, nerve cell
      degeneration, and axonal degeneration in the cerebellar and vestibular nuclei.
      Similar lesions were observed in misonidazole-treated dogs and clioquinol induced
      nerve cell degeneration in the hippocampus and malacia in the piriform lobes of
      these animals. In rats, acrylamide induced degeneration of Purkinje cells.
      Although the mechanism(s) underlying the differential neurotoxicity of high and
      low doses of these neurotoxicants remains unclear, we suggest certain biochemical
      mechanisms, cytotoxic edema and excitotoxicity, as factors in the production of
      such lesions after high-dose treatment.

PMID- 1387791
TI  - Some physical properties of implant abutment luting cements.
AB  - The dislodging force, the compressive strength at 24 hours, and the film
      thickness of four resin composite luting cements (UDA, UDA with fluoride, Panavia
      OP, and DenMat) and a conventional glass-ionomer cement (Shofu Type I) were
      compared. The axial force necessary to dislodge each cemented 0 degree abutment
      from an internally threaded Steri-Oss implant (n = 5) was then determined using a
      mechanical testing machine. UDA with fluoride appears to be a significantly
      stronger luting agent for abutment cementation than is either UDA or DenMat (P
      less than .05). DenMat resin composite cement exhibited the highest mean
      compressive strength whereas Panavia OP had the lowest value for film thickness.

PMID- 1387792
TI  - The captopril renogram in percutaneous transluminal angioplasty of the renal
      arteries.
AB  - Technetium-99m DTPA renograms were performed before and after angioplasty in a 63
      year-old man with bilateral renal artery stenosis (RAS), hypertension, and renal
      insufficiency. Decreased isotope uptake after captopril by the right kidney
      assisted in the selection of the right renal artery for angioplasty. Post
      angioplasty improvement in both blood pressure control and renal function was
      accompanied by an absence of effect of captopril on the isotope uptake by the
      right kidney. In bilateral RAS, the captopril renogram is a useful tool for
      selecting the site for angioplasty, for assessing the adequacy of the procedure,
      and for long-term follow-up.

PMID- 1387793
TI  - [Incidence rates of cerebral palsy, severe mental and motor retardation, and Down
      syndrome in the city of Higashiyamato in suburban Tokyo].
AB  - We investigated the incidence rates of three neurological diseases in childhood
      in the City of Higashiyamato in suburban Tokyo with a total population of about
      70,000. The number of liveborn babies during 1985-1989 was 3,958. The number of
      patients with cerebral palsy (CP) was 9 and the incidence rate was 2.2/1,000,
      which was equal to the reports from several countries. Four out of 9 patients
      with CP had mild motor handicaps and were expected to "outgrow" their handicaps.
      The number of patients with "severe mental and motor retardation" (SMMR) was 4
      and the incidence rate was 1.0/1,000. Prenatal brain damage played a major role
      in the pathogenesis of CP and SMMR. The number of patients with Down syndrome
      (DS) was 7 and the incidence rate was 1.8/1,000. Incidence rates of CP, SMMR, and
      DS still remain high and further strategy to prevent pediatric neurological
      diseases is necessary.

PMID- 1387794
TI  - [A clinical course and autopsy results of an 8-year-old severely handicapped girl
      with marked periventricular leukomalacia].
AB  - We reported a clinical course and autopsy results of an 8-year-old severely
      handicapped girl with marked periventricular leukomalacia. She was well until 3
      days prior to first admission in local hospital. Two days prior to admission, she
      began to vomit. Twelve hours later, she was noted to be lethargic and developed
      malaise with frequent vomiting. At physical examination on admission, she had
      frequent fits and her posture was decerebrate rigidity. Consciousness disturbance
      continued for two weeks. Thereafter, she became severely handicapped with spastic
      quadriplegia, mental retardation and intractable epilepsy. She was transferred to
      our hospital one month later. We cared her totally and carefully with our
      rehabilitation staff, but during her course several rare happening occurred; she
      suffered from subdural hemorrhage due to hypocupremia and received an operation
      for the release of contracture of her hips. She died of acute cardio-respiratory
      failure at 8 years and 5 months of age. Her autopsy findings were characteristic
      of the damage to an immature brain during development; cactus formation of
      cerebellar cortex and periventricular leukomalacia.

PMID- 1387795
TI  - [Laparoscopy in acute appendicitis].
AB  - Our experience shows that laparoscopy is an excellent diagnostic method in cases
      where acute appendicitis is suspected, but when the clinical picture and tests
      are equivocal. Laparoscopy can help diagnose other abdominal conditions mimicking
      acute appendicitis and, in addition, may be used to remove the appendix in most
      cases, with advantages over open surgery.

PMID- 1387796
TI  - Circulating myosin light chain I levels after coronary reperfusion: a comparison
      with myocardial necrosis evaluated from single photon emission computed
      tomography with pyrophosphate.
AB  - This study was performed to assess the influence of coronary reperfusion on the
      serial serum myosin light chain (LC)I levels and to evaluate the relationship
      between the peak LCI level and the infarct size calculated from single photon
      emission computed tomography (SPECT) with technetium-99m pyrophosphate (Tc-99m
      PYP) in 11 patients who underwent coronary reperfusion. Blood was drawn before
      reperfusion, immediately after reperfusion, and once a day for 14 days, to
      estimate the time course of serum LCI release. The infarct size estimated by Tc
      99m PYP ranged from 7.3 to 62.4 ml. The LCI levels obtained before reperfusion
      were less than 2.5 ng/ml but those obtained immediately after reperfusion were
      much higher. The value ranged from 2.7 to 9.7 ng/ml and that expressed as a
      percentage of peak LCI (% peak LCI) ranged from 19 to 83%. Collateral
      circulation, reperfusion arrhythmia and the degree of residual stenosis had no
      influence upon the % peak LCI. The correlation between peak LCI levels and SPECT
      determined infarct size was good, with a correlation of 0.76 (p less than 0.01,
      regression line by least squares method y = 3.31 + 1.53x). Early serum LCI might
      be influenced by coronary reperfusion but the peak LCI value reflected acute
      myocardial necrosis in patients who underwent coronary reperfusion.

PMID- 1387797
TI  - Cardiovascular effects of the novel potassium channel opener bimakalim in
      conscious pigs after myocardial infarction: a comparative study with nicorandil.
AB  - The benzopyran-derivative bimakalim is an ATP-dependent potassium channel
      activator that has been shown to be a potent arterial vasodilator in anesthetized
      pigs. In the present study we evaluated the cardiovascular profile of bimakalim
      in normal conscious animals and conscious animals with chronic left ventricular
      dysfunction and compared the results to those obtained with nicorandil. In normal
      conscious pigs, bimakalim (37.5-300 ng/kg/min, n = 6) and nicorandil (10-80
      micrograms/kg/min, n = 8) increased cardiac output from 2.7 +/- 0.1 l/min to 3.8
      +/- 0.2 l/min and from 2.7 +/- 0.1 l/min to 3.9 +/- 0.3 l/min (both p less than
      .05) due to increases in heart rate (up to 62 +/- 14% and 74 +/- 9%,
      respectively, both p less than .05). The mean arterial blood pressure decreased
      gradually from 104 +/- 4 mmHg to 91 +/- 5 mmHg with bimakalim and from 98 +/- 3
      mmHg to 84 +/- 5 mmHg with nicorandil (both p less than .05), due to similar
      decreases in systemic vascular resistance. LVdP/dtmax also increased with both
      drugs (up to 48 +/- 11% and 69 +/- 7%, respectively, p less than .05), but left
      ventricular end-diastolic pressure remained unchanged with bimakalim, while it
      gradually decreased from 9 +/- 1 mmHg to 5 +/- 1 mmHg (p less than .05) with
      nicorandil. In pigs with a 3- to 4-week-old myocardial infarction, the
      vasodilator responses to bimakalim (n = 8) and nicorandil (n = 9) were not
      affected, but the increases in heart rate and LVdP/dtmax were attenuated compared
      to the effects in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387798
TI  - Effect of disopyramide on left ventricular diastolic function in patients with
      hypertrophic cardiomyopathy: comparison with diltiazem.
AB  - Left ventricular diastolic function before and after the administration of
      disopyramide (100 mg) or diltiazem (30 mg) was assessed in 10 patients with
      nonobstructive type hypertrophic cardiomyopathy. Left ventricular diastolic
      function was assessed by Doppler echocardiography. The peak early (E) and late
      (A) diastolic flow velocities and E/A ratio (E/A) were measured. Three hours
      after the administration of disopyramide, blood pressure did not significantly
      change, but heart rate was decreased significantly (p less than 0.01).
      Disopyramide increased the E velocity and E/A ratio from 43.8 +/- 15.0 cm/sec to
      51.3 +/- 16.1 cm/sec and from 0.71 +/- 0.20 to 1.00 +/- 0.24 (each p less than
      0.01), respectively, and decreased the A velocity from 63.9 +/- 18.5 cm/sec to
      52.1 +/- 14.9 cm/sec (p less than 0.01). Diltiazem increased the E velocity and
      E/A ratio from 42.8 +/- 12.5 cm/sec to 46.4 +/- 13.4 cm/sec (p less than 0.05)
      and from 0.74 +/- 0.21 to 0.96 +/- 0.28 (p less than 0.01), respectively, and
      decreased the A velocity from 60.6 +/- 16.4 cm/sec to 50.2 +/- 15.6 cm/sec (p
      less than 0.01). These results indicate that disopyramide improved left
      ventricular diastolic filling in hypertrophic cardiomyopathy, and its effect was
      similar to that of diltiazem.

PMID- 1387800
TI  - Massive atrial natriuretic peptide (ANP) release in ischemia reperfusion.

PMID- 1387801
TI  - Response of a human megakaryocytic cell line to thrombin: increase in
      intracellular free calcium and mitogen release.
AB  - The CHRF-288-11 cell line has been previously shown to exhibit properties
      consistent with a megakaryocytic origin. The response of these cells to thrombin
      has now been investigated. Thrombin treatment of CHRF-288-11 cells results in
      both an increase in intracellular free calcium levels and secretion of mitogenic
      activity and beta-thromboglobulin. Cell viability is not affected. The mitogenic
      activity released from the cells is due primarily to the presence of basic
      fibroblast growth factor. Immunohistochemical data indicate a packaging of basic
      fibroblast growth factor into granular structures. Trypsin and phorbol 12
      myristate 13-acetate also initiate release of mitogenic activity from this cell
      line, whereas under non-stirred conditions collagen and ADP do not. Through
      measurements of intracellular calcium levels it was determined that thrombin
      pretreatment of cells ablates a further response to thrombin, but does not block
      an increase in intracellular calcium levels due to trypsin. This suggests that
      these two agonists may act through different mechanisms. The thrombin-induced
      release reaction is inhibited almost completely by the reagents hirudin and
      dipyridamole, and only partially by indomethacin. These data indicate that the
      CHRF-288-11 cell line should provide an excellent model system in which to study
      the packaging of factors into granules which undergo regulated release.

PMID- 1387799
TI  - Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin
      converting enzyme inhibitors.
AB  - Recent studies have suggested the beneficial effects of angiotensin converting
      enzyme (ACE) inhibitors against myocardial ischemic-reperfusion injury. This
      study was designed to compare the cardioprotective effects of two sulfhydryl ACE
      inhibitors, captopril and zofenopril, with those of a nonsulfhydryl ACE
      inhibitor, fosinopril. The efficacy of these ACE inhibitors to scavenge oxygen
      radicals in vitro were also examined. Isolated rat hearts perfused by the
      Langendorff technique were preperfused in the presence or absence of ACE
      inhibitors (50 microns for 15 minutes, and the hearts were then subjected to 30
      minutes of ischemia followed by 30 minutes of reperfusion. Zofenopril and
      captopril, but not fosinopril, improved postischemic left ventricular functions
      and reduced myocardial cellular injury, as evidenced by improved recovery of the
      first derivative of left ventricular pressure development and reduced creatine
      kinase release compared with control (p less than .05). Coronary flow was
      significantly increased by captopril and zofenopril only. The same two drugs also
      inhibited the enhanced lipid peroxidation during reperfusion. Although
      significant differences were not noticed in the postischemic myocardial membrane
      phospholipid composition, captopril and zofenopril reduced nonesterified fatty
      acid contents, including palmitic, linoleic, oleic, and arachidonic acids. In
      vitro studies demonstrated that captopril and zofenopril were able to scavenge
      hydroxyl radicals. These results indicate that among three ACE inhibitors, two
      sulfhydryl-containing drugs, captopril and zofenopril, possess cardioprotective
      as well as free-radical scavenging abilities. Attenuation of phospholipid
      degradation and lipid peroxidation may be contributory to the protective effects
      observed in this study.

PMID- 1387802
TI  - Detergent sensitivity of the tonoplast H(+)-ATPase and its purification from Beta
      vulgaris.
AB  - Tonoplast membrane fractions were isolated from beetroot (Beta vulgaris) using a
      refined method of preparation which significantly improved the yield of active
      tonoplast H(+)-ATPase, and electron microscopy showed these fractions to be a
      preparation of small vesicles, of diameter 500 nm to 50 nm and a minor fraction
      consisting of mainly tubular membrane structures of diameter 5 nm and length up
      to 1 micron. The stability of the tonoplast H(+)-ATPase was assessed in the
      presence of many biological detergents, using a linked assay. The addition of
      detergent to tonoplast membranes generally led to an increase in ATPase activity,
      and activity was maintained in a wide range of both non-ionic and zwitterionic
      detergents. Using the non-ionic detergent dodecyl maltoside, the tonoplast H(+)
      ATPase was partially purified using ion-exchange chromatography on an HPLC
      system. Very high rates of ATP hydrolysis were recorded in these fractions. The
      purified membranes behaved as expected in the presence of known activators and
      inhibitors. An unexpected observation, however, was that low concentrations of
      vanadate could significantly increase the rate of H(+)-ATPase activity.

PMID- 1387804
TI  - Structural modeling of the human erythrocyte bisphosphoglycerate mutase.
AB  - Using the crystallographic structure of yeast monophosphoglycerate mutase (MPGM)
      as a framework we constructed a three-dimensional model of the homologous human
      erythrocyte bisphosphoglycerate mutase (BPGM). The modeling procedure consisted
      of substituting 117 amino acid residues and positioning 19 C-terminal residues
      (unresolved in the X-ray structure) by empirical methods, followed by energy
      minimization. Among several differences in the active site region the most
      significant appears to be the replacement of Ser11 in MPGM by Gly in BPGM. The C
      terminal segment, which contains mainly basic amino acids, lines the cavity of
      the active site. The seven amino acid residues, which have been shown to be
      essential for the three catalytic functions of the human BPGM, interact with the
      amino acids in the protein core, near the active site. In addition, a cluster of
      several positively charged residues, particularly arginines, has been identified
      at the entrance of the active site; this cluster may serve as a secondary binding
      site for polyanionic substrates or cofactors, as required by a two-binding-site
      model of the catalytic activities. This model is in agreement with recent studies
      of an inactive BPGM variant substituent at an Arg position situated in this
      positively charged cluster. The position of Cys20 in the model constructed
      suggests that this residue is responsible for inactivation of the enzyme by
      sulfhydryl reagents. Subunit interfaces have also been constructed for BPGM by
      analogy with MPGM and suggest that, in addition to the known dimerization of
      BPGM, tetramerization may occur under certain conditions.

PMID- 1387803
TI  - Efficient photoaffinity labeling of human beta-hexosaminidase A. Synthesis and
      application of 3-azi-1-[(2-acetamido-2-deoxy-1-beta- D-glucopyranosyl)thio]- and 
      galactopyranosyl)thio]butane.
AB  - Two photolabile thioglycosides (8 and 9) were synthesized by Koenigs-Knorr type
      glycosylation. These compounds, being enzyme-resistant analogues of N
      acetylhexosaminides, were shown to be good competitive inhibitors of lysosomal
      beta-hexosaminidase (2-acetamido-2-deoxy- beta-D-hexoside
      acetamidodeoxyhexohydrolase, EC 3.2.1.52) action. For photoaffinity labeling 3H
      labeled 8a was prepared by enzymatic oxidation with galactose oxidase followed by
      reduction with sodium [3H]borohydride. Compound 8a, when photolyzed in the
      presence of hexosaminidase, specifically labeled both subunits of the enzyme.

PMID- 1387805
TI  - Evaluation of intraventricular teicoplanin for the treatment of neurosurgical
      shunt infections.
AB  - Seven patients with staphylococcal neurosurgical shunt infections were treated
      with intraventricular teicoplanin. Two infants received 5 mg/d, three patients
      received 20 mg/d, and two patients received 20 mg every other day. Six of these
      patients also received intravenous antibiotics. Three patients had infections
      caused by methicillin-susceptible Staphylococcus epidermidis, and one patient had
      an infection caused by methicillin-resistant S. epidermidis. Three patients were
      infected with Staphylococcus aureus (one with a methicillin-resistant strain and
      two with methicillin-susceptible strains). The mean duration of intraventricular
      therapy was 16 days. Sterilization of cerebrospinal fluid (CSF) was obtained
      after an average of 4.4 days. All patients were cured both clinically and
      microbiologically. No significant adverse effects were observed in any patients.
      Penetration of teicoplanin into the CSF after intravenous administration was
      poor. However, after intraventricular administration, high and prolonged peak and
      trough levels of teicoplanin were detected in the CSF. Bactericidal activity of
      the CSF was remarkable, exceeding the 1:8 dilution in the majority of the cases.
      The alternate-day schedule of intraventricular administration of teicoplanin was
      as effective as the once-daily regimen.

PMID- 1387806
TI  - Piperacillin plus amikacin vs. piperacillin plus amikacin plus teicoplanin for
      empirical treatment of febrile episodes in neutropenic patients receiving
      quinolone prophylaxis.
AB  - A prospective, randomized trial was initiated to evaluate the efficacy of two
      antibiotic regimens, differing in the agent included with activity against gram
      positive bacteria, for the empirical treatment of febrile episodes in neutropenic
      patients with hematologic malignancies (group 1, piperacillin plus amikacin;
      group 2, piperacillin plus amikacin plus teicoplanin). After 72 hours of therapy,
      patients in group 1 who were still febrile were administered teicoplanin and
      those in group 2 were administered amphotericin B. A total of 158 evaluable
      episodes were observed within 8 months. The success rate was 50.6% in group 1 and
      60% in group 2. The response rate among patients who did not respond to the
      original regimen increased to 86.7% with the addition of teicoplanin (group 1)
      and to 90% with the addition of amphotericin B (group 2). There were 86
      unexplained febrile episodes and 56 documented episodes of bacteremia (34 caused
      by gram-positive organisms). Our results indicate that teicoplanin is safe, well
      tolerated, and effective for the treatment of documented episodes of gram
      positive bacteremia and as an empirical agent. The inclusion of teicoplanin in
      the initial empirical regimen appears unnecessary if a combination of antibiotics
      active against gram-positive organisms is used, unless infections are due to
      oxacillin-resistant staphylococci.

PMID- 1387807
TI  - Enterococcus species in urinary tract infection.
AB  - Significant urinary isolates have been prospectively recorded since 1971.
      Enterococcus species, a common cause of nosocomial urinary tract infection, have
      been identified, and susceptibilities to a range of antibiotics have been
      determined. In addition, isolates in 1988 were tested for breakpoint
      susceptibility to vancomycin and teicoplanin. Despite changes in the hospitals
      covered, isolation of Enterococcus species rose steadily from 4% in 1971 to 12.6%
      in 1990 in hospital patients and from 2% to 5.6% in general-practice patients (P
      less than .01). All isolates of Enterococcus species were sensitive to
      ampicillin. Teicoplanin inhibited all 526 strains tested at a concentration of 2
      micrograms/mL, but the same concentration of vancomycin inhibited only 370 (70%).
      The increased prevalence of enterococcal urinary tract infection is probably the
      result of increasing use of catheterization and broad-spectrum antibiotics.
      Glycopeptides reach high levels in the urine, and teicoplanin might be an
      alternative for the treatment of urinary tract infections due to enterococci.

PMID- 1387808
TI  - Efficacy of teicoplanin for enterococcal infections: 63 cases and review.
AB  - Sixty-three cases of monomicrobial enterococcal infections treated with
      teicoplanin in two open clinical studies in Europe from 1982 to 1989 are
      presented. Infections were documented as endocarditis (n = 18); septicemia (n =
      8); and urinary tract (n = 29), skin/soft-tissue (n = 6), or bone/joint (n = 2)
      infections. A total of 63 enterococcal strains were isolated; all of 29 strains
      tested were susceptible to teicoplanin (geometric mean MIC, 0.16 micrograms/mL;
      range, 0.06-0.5 micrograms/mL). Forty-eight patients were treated with
      teicoplanin alone and 15 were treated with teicoplanin in combination with an
      aminoglycoside. The rate of clinical cure was 84.1%; 4.8% of patients clinically
      improved, 7.9% had clinical recurrence, and 3.2% did not respond to therapy.
      Bacteriologic eradication was observed in 87.2% of patients; persistence, in
      3.2%; recurrence, in 3.2%; and reinfection, in 4.8%. One case was not evaluable
      bacteriologically. Of 18 patients with endocarditis, 15 were cured with a mean
      daily dose of 5.4 mg/kg--six with monotherapy and nine with combination therapy.
      All patients with urinary tract infections were treated with monotherapy, and
      89.7% were cured (mean daily dose, 4.6 mg/kg). Lower rates of clinical cure and
      bacteriologic eradication were observed in septicemic patients without
      endocarditis (62.5%). This study demonstrated a good efficacy of teicoplanin for
      the treatment of enterococcal infections due to susceptible strains, but further
      clinical studies would be useful for establishing optimal dosage and the
      indications for combination therapy, especially for severe infections.

PMID- 1387809
TI  - Localized cutaneous reaction to intravenous pentamidine.

PMID- 1387810
TI  - Clarithromycin-induced thrombocytopenia.

PMID- 1387811
TI  - Tri-iodothyronine regulates survival and differentiation of rat cerebellar
      granule neurons.
AB  - The effects of tri-iodothyronine (T3), which are known to affect cerebellar
      development, were tested on neuronal survival and differentiation of cultured
      cerebellar granule neurons. T3 in physiological concentrations increased both
      granule neuron survival after three days in culture and synaptic vesicle protein
      formation, as shown by immunostaining with antibodies against synaptophysin.
      Likewise, T3 increased the mRNA level for synapsin(I), but not that for GAP43 in
      granule neurons. Antibodies against microtubule associated protein Tau, which is
      expressed in developing neurites, showed that T3 also enhanced neurite formation.

PMID- 1387812
TI  - Influence of target tissues on their innervation in old age: a transplantation
      study.
AB  - Age-related changes in the nervous system might be intrinsic to the neurons or
      secondary to changes in the target tissues they supply. We have investigated this
      question by transplanting old and young vascular muscle into contact with young
      host nerves in oculo and observing the reinnervating nerve fibres. The density
      and pattern of reinnervation were those typical of the age of the target tissue,
      thus old transplants imposed an 'old' pattern of reinnervation on young host
      nerves. Our findings strongly support the hypothesis that target tissues
      determine the pattern and density of their innervation in old age.

PMID- 1387813
TI  - Disruption of the SCL locus in T-lymphoid malignancies correlates with commitment
      to the T-cell receptor alpha beta lineage.
AB  - The SCL/tal-1 gene on chromosome 1 is disrupted in up to 30% of immature T-cell
      malignancies, thus representing the most commonly recognized chromosomal
      abnormality in this disorder. Abnormalities of the gene occur rarely by
      chromosomal translocation into the T-cell receptor (TCR) delta locus and commonly
      by a site-specific 95-kb deletion, SIL-SCL (tald). Analysis of the SIL-SCL
      deletion by Southern blotting and polymerase chain reaction (PCR) in a series of
      52 immature T-cell malignancies showed a type A deletion in 21% of cases, but no
      type B deletions. The type A deletion correlated with malignancies of the TCR
      alpha beta lineage, either on the basis of TCR alpha beta expression or bilateral
      TCR delta deletion. Fifty percent (5 of 10) of TCR alpha beta-expressing cells
      demonstrated the abnormality, whereas 0% (0 of 11) of TCR gamma delta-expressing
      cells did so. Six of eight SIL-SCL type A cases had undergone bilateral delta
      deletion, whereas only one of 31 cases with an apparently normal SCL gene had
      done so. These data demonstrate an association between SCL disruption and TCR
      alpha beta lineage differentiation and suggest that the SIL-SCL deletion occurs
      at the same stage of ontogeny as TCR delta deletion.

PMID- 1387814
TI  - Unusual diffuse liver fibrosis accompanying transient myeloproliferative disorder
      in Down's syndrome: a report of four autopsy cases and proposal of a hypothesis.
AB  - Transient myeloproliferative disorder (TMD), an acute leukemia-like disorder in
      neonates with Down's syndrome, is characterized by spontaneous regression of
      abnormal blast growth. Because proliferating blasts frequently express phenotypes
      of megakaryocytic lineage and, as a result, this disorder resembles acute
      megakaryoblastic leukemia (AMKL), it would be of interest to determine whether
      myelofibrosis, a common complication of AMKL, is also present in TMD. Pathologic
      observations of four autopsy cases of TMD showed that myelofibrosis was not
      present in any of them, whereas intralobular diffuse liver fibrosis was present
      in all of them. Laboratory data of four additional cases showed hepatic
      dysfunction in all of them, suggesting a close association between hepatic
      lesions and TMD. From these results, we propose a hypothesis that the abnormal
      blasts with megakaryocytic properties in TMD originate from the fetal liver and
      cause liver fibrosis, as AMKL cells are thought to cause myelofibrosis by
      producing collagen-stimulating cytokines in the bone marrow. This hypothesis also
      seems to explain some other unique aspects of TMD.

PMID- 1387815
TI  - Categories, classes and criteria in childhood disability--experience from a
      survey in Jamaica.
AB  - This paper reports a new classification and criteria for disabilities and
      handicaps used in a survey of childhood disability in Jamaica. Part of the
      International Classification of Impairments, Disabilities and Handicaps was used,
      with an alternative classification for disabilities similar to that of
      impairment, and with a complete set of criteria for levels of severity. For
      handicaps, the set proposed in the WHO manual, Training Disabled People in the
      Community, was used. No difficulties were encountered in the use of definitions
      or severity criteria. The inter-rater reliability for disability as a whole by
      community workers was 79% (kappa statistic 0.58), and for the physician and
      psychologist 90 and 100%. The handicap classification was easy to use but there
      was some confusion with resulting poor inter-rater reliability for some
      questions. This could be corrected by clarification of the meaning of the
      questions during training. We recommend use of this classification and criteria
      as being simple and realistic for surveys of childhood disability conducted by
      community workers.

PMID- 1387816
TI  - Assessing the function of functional assessment: a consumer perspective.
AB  - The person who is most affected by the process of functional assessment is the
      consumer--the individual with a disability whose functional capacity is being
      assessed. Consumers want the functional assessment process to be conducted in a
      dignified manner and the results to be relevant to their needs. Many consumers,
      influenced by the independent living movement, focus primarily on their ability
      to live independently in their communities and on environmental barriers that
      prevent them from doing so. Yet, most functional status measures focus primarily
      on impairments and functional limitations, rather than on handicapping
      environmental factors. Consumers should be involved directly in the development
      and application of functional status measures so that these factors are
      considered appropriately. Such measures have important implications for defining
      programme eligibility, determining payment, assuring quality, and enhancing
      discharge planning.

PMID- 1387817
TI  - Lecithin cholesterol acyltransferase in human cerebrospinal fluid: reduced level
      in patients with multiple sclerosis and evidence of direct synthesis in the
      brain.
AB  - Several studies suggest that apolipoproteins and the low-density lipoprotein
      receptor are implicated in lipid transport in the brain. Given that cerebrospinal
      fluid has been reported to contain cholesteryl esterifying enzyme, and that lipid
      metabolism in the brain is abnormal in subjects with multiple sclerosis, we
      examined the cerebrospinal fluid from eight control subjects with a normal
      cerebrospinal fluid IgG index, and without active demyelinating disease, and from
      eight subjects (6 were diagnosed as having multiple sclerosis) with an increased
      IgG index and the presence of oligoclonal banding in the cerebrospinal fluid, for
      the presence of the enzyme lecithin cholesterol acyltransferase and
      apolipoprotein(a). None of the subjects demonstrated impairment of their blood
      cerebrospinal fluid barrier, as estimated by the cerebrospinal fluid/serum
      quotient of albumin. Lecithin cholesterol acyltransferase was detected in the
      cerebrospinal fluid of all control subjects, being 0.12 +/- 0.06 microgram/ml
      (mean +/- SD) or about 2.2% of that in serum (5.4 +/- 1.4 micrograms/ml). The
      cerebrospinal fluid lecithin cholesterol acyltransferase index was 5.2 +/- 2.5,
      very similar to the cerebrospinal fluid index of apolipoprotein E, a protein
      known to be synthesized in the brain. Since lecithin cholesterol acyltransferase
      mRNA is also expressed in the brain, we can conclude that the protein is
      synthesized and secreted in the brain. The cerebrospinal fluid concentration of
      lecithin cholesterol acyltransferase in the subjects with active demyelinating
      disease or multiple sclerosis was only about one-half of that found in control
      subjects (0.06 +/- 0.02 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387818
TI  - Automated measurement of lipoprotein(a) by immunoturbidimetric analysis.
AB  - Immunoturbidimetric analysis of lipoprotein(a) in plasma or serum was developed
      for use on the Roche COBAS FARA II and COBAS MIRA clinical chemistry analyzers.
      The components of the assay are: (1) buffer consisting of 2.25% polyethylene
      glycol in phosphate-buffered saline, 0.2% gelatin, and a surfactant; (2)
      fractionated goat anti-human lipoprotein(a) IgG; (3) five standards with
      lipoprotein(a) concentrations ranging from 0.05 to 1.0 g/l; (4) two controls with
      concentrations of approximately 0.2 and 0.5 g/l. The analyzer delivers sample and
      buffer, incubates the reaction mixture at 37 degrees C for 5 min, delivers neat
      lipoprotein(a) antibody, and incubates for an additional 10 min. The
      lipoprotein(a) concentration of samples is calculated by the COBAS DENS (Data
      Evaluation for Non-linear Standard Curves) option by fitting the standard curve
      values to a four-parameter logit-log curve model. Total imprecision results (CV%)
      for the FARA II and MIRA were under 11% (NCCLS protocol EP5-T). The assay is
      linear beyond the highest calibrator to 2.6 g/l. No interference was observed for
      plasminogen up to 2.3 g/l, apolipoprotein B up to 4.36 g/l, hemoglobin up to 10
      g/l, bilirubin up to 4.0 g/l, and triglycerides up to 4.36 g/l. Comparison with a
      double monoclonal ELISA used at the Northwest Lipid Research Laboratories
      yielded: R = 0.970, slope = 1.013, and y-intercept = 0.00009 (n = 37). Comparison
      with a commercially available ELISA kit for lipoprotein(a) yielded: r = 0.987,
      slope = 1.243, and y-intercept = 0.024 (n = 40). This assay provides rapid,
      accurate, and precise screening of lipoprotein(a) in serum or plasma.

PMID- 1387819
TI  - Update on technology assessment in dentistry.
AB  - This review focuses on evaluations of particular clinical problems or
      technologies in dentistry that have used the recently developed technology
      assessment techniques of decision analysis, meta-analysis, and cost-effectiveness
      analysis. It also discusses general methodologic and implementation issues in the
      assessment of health-care technologies.

PMID- 1387820
TI  - Anthropometry, spinal canal width, and flexibility of the spine and hamstring
      muscles in 45-55-year-old men with and without low back pain.
AB  - One hundred fifty 45-55-year-old men were divided into three groups: those with
      healthy backs, recurrent low back pain (LBP), and chronic LBP. These groups were
      studied with respect to anthropometry, spinal canal width, spinal sagittal
      configuration and flexibility, and the flexibility of the hamstrings musculature
      with straight leg raising (SLR). There were no differences between the groups
      with respect to anthropometry. The group with healthy backs had significantly
      greater lordosis and sagittal flexibility than the other groups. The width of the
      spinal canal was correlated to body height. The SLR test showed significantly
      higher values in the group with healthy backs and in the recurrent pain group
      than in the chronic pain group. The possible role of restoring normal range of
      motion to minimize the risk of LBP recurrence is discussed.

PMID- 1387821
TI  - Expert performance in low-back disorder recognition using patient pain drawings.
AB  - Eight low-back-pain experts who regularly include pain drawings in their clinical
      workup were asked to classify 25 drawings. The experts used only the drawings to
      place cases into one of five broadly defined diagnostic categories: benign
      disorder, herniated disc, spinal stenosis, underlying disorder, or psychogenic
      disturbance. The physicians demonstrated adequate accuracy--51% correct--when
      compared with change (20% correct). Classification accuracy was greatest for
      psychogenic disorders (85%), followed by spinal stenosis (58%), herniated discs
      (52%), and benign disorders (50%). Predictions were comparatively poor for the
      underlying disorder category (10%). The individual physician accuracies varied
      from 44 to 60%. "Classic" pain patterns for each disorder group were identified
      by determining which drawings were correctly classified by most physicians.
      Physicians may wish to impart greater significance to pain drawings close to one
      of our "classic" patterns than to others.

PMID- 1387822
TI  - Effects of lumbar belts on trunk muscle strength and endurance: a follow-up study
      of construction workers.
AB  - The effects on maximal isometric trunk muscle strength and endurance after
      wearing a soft heat-retaining lumbar belt or a weightlifter's belt were studied.
      The soft belt (SB) study group comprised 12 construction workers with healthy
      backs, and the weightlifter's belt (WB) group comprised 24 construction workers
      with current or previous low back pain. The strength and endurance measurements
      were performed before the start of belt use, and after 1 and 2 months. The SB
      group increased the trunk flexor strength by 13% (p less than or equal to 0.01)
      after 2 months. The WB group increased the trunk flexor strength and endurance by
      12% and 29%, respectively (p less than or equal to 0.001). No significant
      decrease of trunk muscle strength and endurance was found at the end of the
      follow-up period.

PMID- 1387823
TI  - The role of prior knowledge on back-pain education.
AB  - To investigate the effectiveness of the Geneva Back School (BS), we studied
      certain aspects of the retention of what was taught and the changes it induced in
      the patients. Thirty-nine BS patients were asked to draw their backs both before
      and after the BS. They were also asked to define the terms arthrosis and
      herniated disc once before the BS and twice after the program. Analysis of 78
      drawings showed that the representation of the back was far from anatomical
      reality in both instances. The definitions of terms correlated poorly between
      patients and health care professional before BS. Teaching increased patient
      knowledge, but did not delete patients' prior notions. Our findings indicate that
      teaching strategies need to take into account patients' beliefs and knowledge.
      Health care professionals involved in BS programs should also be aware of the
      possible misunderstanding of medical terms. These factors may explain, at least
      partially, BS failures.

PMID- 1387824
TI  - Segmental fixation of lumbar burst fractures with Cotrel-Dubousset
      instrumentation.
AB  - A retrospective review of 17 patients who underwent bilateral transpedicular
      decompression, instrumentation with a Cotrel-Dubousset construct, and
      posterolateral fusion with iliac crest bone graft for treatment of lumbar burst
      fracture is presented. All patients were followed to fusion with an average
      follow-up of 18.9 months. Fifteen of sixteen patients returned to preinjury
      occupation and/or activity. All patients reported good to excellent clinical
      results. The average postoperative progression of kyphosis was 11.9 degrees.
      There was no significant change in anterior vertebral height between the
      preoperative and postoperative periods. We conclude that although excellent early
      clinical results can be obtained using this operative strategy, the long-term
      effect of residual kyphosis at the fracture site is unknown.

PMID- 1387825
TI  - [Survival in esophageal cancer in high altitude].
AB  - Records of 5474 esophageal cancer patients treated in 1959-1983 have been
      analyzed. The patients came from various climatic and geographical zones of the
      high-mountain region. A correlation has been found between the survival of the
      patients, scope of the disease-oriented aid and hypoxia of high mountains. Total
      cumulative values are presented for survival of esophageal cancer patients by
      five-year intervals in various medico-geographical zones of high mountains and
      according to methods of treatment.

PMID- 1387826
TI  - [Status and prospects of the development of traumatological and orthopedic
      services in the Moscow district].

PMID- 1387828
TI  - Phenotypic analysis of the chicken thymic microenvironment during ontogenic
      development.
AB  - The development of monoclonal antibodies (mAb) reactive with the thymic
      microenvironment has identified distinct subpopulations within the stromal
      component, but the function of these subregions in intrathymic T-cell
      differentiation remains essentially an enigma. In this study, we have used such a
      panel of mAb to examine the chicken thymus during ontogenic development to gain
      insight into the contributions of these thymic regions to the distinct phases of
      T-cell development and to further characterize the development of this organ. Our
      reagents have demonstrated the complex differentiation of the primitive
      endodermal epithelium into more specialized structures and the development of
      other thymic stromal components from mesectodermal cells. We also describe
      molecules localized to the subcapsular and perivascular regions, which have an
      ontogenic expression corresponding to the early localization and stimulation of
      thymic precursors and another molecule on the medullary vasculature expressed
      corresponding to the exit of mature cells from the thymus. In addition, two
      markers of distinct medullary epithelial clusters are initially expressed
      corresponding to the appearance of T-cell receptor-1 (TcR-1) and TcR-2 positive
      cells in the medulla, respectively. These mAb potentially represent excellent
      reagents for further definition of the thymic modulation of T-cell
      differentiation.

PMID- 1387827
TI  - A role for IgE in extrinsic allergic alveolitis?
AB  - Receptors for the Fc portion of immunoglobulin E (IgE; CD23) can be detected on
      the surface of alveolar macrophages (AM) in extrinsic allergic alveolitis (EAA),
      using monoclonal antibodies in immunocytology. More than 50% of AM were positive
      in 16 of the 20 patients reported here, while the remaining 4 had 11-47% positive
      cells. Staining with anti-IgE antibody can, in addition, demonstrate endogenous
      IgE bound to the AM. This suggests that IgE might be involved in the process.
      Since IgE-mediated asthma is associated with bronchoconstriction, we asked
      whether EAA patients do in fact exhibit an obstructive component. In 3 out of 10
      patients we did indeed find clearly increased airway resistance (greater than 30
      kPa x s x l-1). These findings are consistent with the observation of immediate
      bronchoconstriction observed in some patients upon allergen challenge. Since only
      1 of the 20 patients studied was a smoker, and since in the literature the
      majority of reported cases of EAA are in nonsmokers, we speculate that smoking
      may interfere with immunological processes leading to EAA.

PMID- 1387829
TI  - Phenotypic characterization of chicken thymic stromal elements.
AB  - Phenotypic profiles of the thymic stromal components provide an excellent
      approach to elucidating the nature of the microenvironment of this organ. To
      address this issue in chickens, we have produced an extensive panel of 18 mAb to
      the thymic stroma. These mAb have been extensively characterized with respect to
      their phenotypic specificities and reveal that the stromal cells are equally as
      complex as the T cells whose maturation they direct. They further demonstrate
      that, in comparison to the mammalian thymus, there is a remarkable degree of
      conservation in thymic architecture between phylogenetically diverse species.
      Eleven mAb reacted with thymic epithelial cells: MUI-73 was panepithelium, MUI-54
      stained all cortical and medullary epithelium but only a minority of the
      subcapsule, MUI-52 was specific for isolated stellate cortical epithelial cells,
      MUI-62, -69, and -71 were specific for the medulla (including Hassall's corpuscle
      like structures), MUI-51, -53, -70, and -75 reacted only with the type-1
      epithelium, or discrete regions therein, lining the subcapsular and perivascular
      regions and MUI-58 demonstrated the antigenic similarity between the subcapsule
      and the medulla. Seven other mAb identified distinct isolated stromal cells
      throughout the cortex and medulla. Large thymocyte-rich regions, which often
      spanned from the outer cortex to medulla, lacked epithelial cells. These mAb
      should prove invaluable for determining the functional significance of thymic
      stromal-cell subsets to thymopoiesis.

PMID- 1387830
TI  - Advances in GVHD: novel lymphocyte subsets and cytokine dysregulation.

PMID- 1387831
TI  - Blocking NMDA receptors or nitric oxide production disrupts light transmission to
      the suprachiasmatic nucleus.
AB  - Retinal stimulation with a brief pulse of light (200 lx, 3 min) stimulated heart
      rate in dark-adapted urethane-anaesthetized rats. This effect was inhibited by
      prior infusion of a competitive blocker of N-methyl-D-aspartate (NMDA) receptors,
      (+-)-3-(2-carboxypiperazin-4-yl)-propyl-L-phosphonic acid (CPP, 20 nmol) into the
      hypothalamic suprachiasmatic nucleus (SCN) region. Furthermore, this inhibition
      of the stimulatory effect of light on heart rate was mimicked by prior infusion
      in the SCN region of a competitive blocker of nitric oxide (NO) production from L
      arginine, NG-nitro-L-arginine methyl ester (40 nmol), or a blocker of the soluble
      guanylate cyclase. Methylene blue (20 nmol). None of these effects was seen when
      infusions were made in a region located 2 mm dorsal to the SCN or when a non
      visual stimulus (tail pinch) was used to stimulate heart rate. These results
      point to a functional link between activation of an NMDA receptor coupled NO/cGMP
      signalling pathway and light transmission to the SCN.

PMID- 1387832
TI  - Arcaine and magnesium inhibition of the NMDA receptor ionophore complex: evidence
      for distinct voltage-dependent sites.
AB  - The inhibitory effects of the polyamine antagonist, arcaine, and magnesium on N
      methyl-D-aspartate (NMDA) induced hippocampal [3H]norepinephrine release and
      [piperidyl-3,4-3H(N)]-[N-1-(2- thienyl)cyclohexyl]-3,4-piperidine (TCP) binding
      were studied. We report that the inhibitory effect of arcaine and magnesium on
      NMDA-induced [3H]norepinephrine release is diminished by increasing the
      extracellular K+ concentration, presumably reflecting a voltage-dependent block
      for both. However, unlike MK-801, the block by arcaine shows no evidence of use
      dependence. Further, the IC50 value for magnesium inhibition of [piperidyl-3,4
      3H(N)]TCP binding varies with the state of activation of the channel, being the
      lowest when the channel is maximally activated and the highest when the channel
      is least activated. On the other hand, the apparent affinity of arcaine is not
      significantly affected by the activation of the channel by glutamate and glycine,
      but is decreased by the polyamine agonist, spermidine. These data suggest that
      the polyamine antagonist binding site is distinct from either the
      phencyclidine/MK-801 site or the voltage-dependent channel site for magnesium.
      Nonetheless, these data suggest that the site must be located in a region of the
      NMDA receptor ionophore complex capable of sensing transmembrane potential.

PMID- 1387833
TI  - Detection of canine homologs of human MYC, BCL2, IGH, and TCRB genes by Southern
      blot analysis.
AB  - Subsets of non-Hodgkin's lymphoma in humans have been shown to involve activation
      of protooncogenes such as MYC and BCL2 resulting from chromosome translocation
      involving the IGH and TCR genes. Malignant lymphomas in the canine present
      histologic and clinical subsets similar to those in humans. To study the genetic
      nature of these lymphomas, we undertook this study to determine, by Southern
      blotting analysis, the extent of homology between the human and canine genes MYC,
      BCL2, IGH, and TCRB using human gene probes. Our results, presented here, show
      that the organization of these genes in the two species is very similar.

PMID- 1387834
TI  - Dental management of patients with spinal cord injury.

PMID- 1387835
TI  - Precipitation of an Addisonian crisis during dental surgery: recognition and
      management.

PMID- 1387836
TI  - Dopamine D1 and D2 antagonists block L-dopa-elicited air-stepping in neonatal
      rats.
AB  - When administered to rat pups that have been suspended in air, L-3,4
      dihydroxyphenylalanine (L-DOPA) induces a highly stereotypic locomotor response
      referred to as air-stepping. In order to determine the respective roles of
      dopamine D1 and D2 receptors in the expression of air-stepping, the abilities of
      the selective D1 antagonist SCH 23390 and the selective D2 antagonist spiperone
      to block L-DOPA-induced air-stepping in 5-day-old rat pups were assessed. Both
      antagonists increased latency to onset, and both decreased total duration of air
      stepping by decreasing the number and length of air-stepping episodes. Neither
      SCH 23390 nor spiperone altered the topography of the air-stepping response;
      however, subjects receiving lower doses of spiperone spent significantly more
      time with the body dorsiflexed and limbs extended (extension/tremor activity)
      than did control subjects. The results suggest that both the D1 and D2 receptor
      subtypes are involved in the production of L-DOPA-induced locomotor activity.

PMID- 1387837
TI  - Percutaneous techniques for the management of symptomatic gallbladder stones.
AB  - Several non-operative treatments for the management of patients with symptomatic
      gallstones have been developed with the purpose of avoiding the considerable
      morbidity associated with open cholecystectomy. Minimally invasive techniques
      utilizing direct percutaneous puncture of the gallbladder are being increasingly
      used for the diagnosis and treatment of gallbladder disease and are the subject
      of this review. With the emergence of laparoscopic cholecystectomy the role of
      these techniques is less certain but they are likely to continue to be important
      in the management of high risk, elderly or medically unfit patients.

PMID- 1387838
TI  - Atrial and brain natriuretic peptides: secretion during exercise in patients with
      essential hypertension and modulation by acute angiotensin-converting enzyme
      inhibition.
AB  - 1. This study examined whether brain and atrial natriuretic peptides (BNP, ANP)
      are secreted together through the coronary sinus from the heart, and whether
      plasma concentrations of BNP and ANP were affected by ergometric exercise in
      patients with essential hypertension. The effects of temocapril, a potent
      angiotensin-converting enzyme (ACE) inhibitor, on plasma concentrations of these
      peptides was also examined. 2. The plasma concentrations of immunoreactive (ir)
      BNP and ir-ANP in the coronary sinus in seven patients with ischaemic heart
      disease during cardiac catheterization were far greater than values with plasma
      obtained at the same time from the femoral artery. 3. The plasma concentrations
      of ir-BNP and ir-ANP increased with exercise and were correlated with each other.
      Temocapril reduced the blood pressure and slightly (but significantly) decreased
      the levels of both peptides at rest and during exercise. 4. The results suggest
      that BNP and ANP were secreted together through the coronary sinus from the
      heart. The secretion was increased by exercise and suppressed by acute ACE
      inhibition. The increase in these peptides during exercise may reflect a
      compensatory mechanism against further elevation of blood pressure.

PMID- 1387839
TI  - Inappropriately elevated levels of atrial natriuretic peptide may contribute to
      the pathophysiology of orthostatic hypotension.
AB  - 1. Overnight recumbent and upright plasma atrial natriuretic peptide (ANP) levels
      were markedly elevated (P less than 0.001) in patients with orthostatic
      hypotension (OH). 2. Overnight urinary clearance of ANP was significantly lower
      (P less than 0.01) in patients with OH, and was inversely correlated with plasma
      ANP levels (r = -0.94, P less than 0.01). The same negative correlation (r = 
      0.87, P less than 0.01) was seen in normal subjects. 3. Reduced urinary clearance
      of ANP may be associated with reduced filtered load and increased binding of ANP
      to the neutral endopeptidase 24.11 receptor binding sites in the proximal renal
      tubule. 4. ANP may be involved in the pathophysiology of orthostatic hypotension.

PMID- 1387840
TI  - Subpressor calcium infusion increases isovolumic left ventricular relaxation time
      and atrial natriuretic peptide in humans.
AB  - 1. Subpressor calcium infusion for 1 h, which raised calcium levels to the upper
      limit of normal in normal subjects, increased plasma and urinary levels of atrial
      natriuretic peptide (ANP). 2. Heart rate fell, presumably due to carotid
      baroreflex stimulation (supported by the fall in noradrenaline) and the resultant
      fall in cardiac output prevented the expected rise in blood pressure due to the
      rise in total peripheral resistance (TPR). Thus the increase in ANP was not
      explained by an increase in blood pressure or noradrenaline. 3. There was no
      evidence for increased atrial stretch (no increase in atrial area or early
      velocity of left ventricular filling) as a mechanism for increased ANP. 4.
      Isovolumic left ventricular relaxation time increased, early velocity of
      ventricular filling decreased and TPR increased, consistent with increased tone
      in left ventricular and arteriolar muscle. 5. This suggests a direct effect of
      calcium on the atrial myocyte, stimulating ANP either through contractile or
      secretory mechanisms.

PMID- 1387841
TI  - Prostaglandins and systolic blood pressure, but not angiotensin II, independently
      affect atrial natriuretic peptide levels in man.
AB  - 1. Two hours after a single dose of indomethacin (INDO), plasma renin activity
      (PRA) and atrial natriuretic peptide (ANP) levels decreased, which is consistent
      with an effect of lowering prostaglandins (PG). 2. After 48 h of INDO, PRA
      remained low but ANP had increased, which is consistent with the known effect of
      prostaglandin inhibitors to cause sodium retention, with a resulting volume
      expansion. 3. Infusions of angiotension II (AII), which raises diastolic blood
      pressure (BP) 20 mmHg or more, consistently raised ANP levels. The ANP response
      to AII infusion was reduced 48 h after INDO, which is consistent with an
      important role for PG in AII-stimulated ANP release. 4. After PG were blocked
      with INDO, the stimulating effect of AII on ANP at doses that increased diastolic
      BP less than 20 mmHg was insignificant, whereas before INDO it was significant.
      5. In dose-response studies, INDO increased the systolic BP response but
      decreased the ANP response to AII, which is consistent with a direct effect of PG
      on ANP that is independent of systolic BP. 6. Prostaglandins and BP are important
      in the ANP response to AII infusion in normal subjects, but AII itself appears to
      have little direct effect on ANP.

PMID- 1387842
TI  - Development and validation of echocardiographic methods for estimating left
      ventricular mass in rats.
AB  - 1. The aim of this study was to develop non-invasive echocardiographic methods of
      measuring left ventricular mass (LVM) in rats, and to determine their usefulness
      in detecting left ventricular hypertrophy. 2. After initial studies to identify
      the optimum transducer and to ascertain the resolution limits of
      echocardiography, the repeatability of LVM estimates was studied. The average
      difference between two independent estimates in 86 male rats (average LVM = 674.7
      mg) was 5.4 mg, and the standard deviation of the difference was 107.6 mg. 3. To
      determine agreement between direct and indirect methods, LVM was measured in 38
      male rats by echocardiography and compared with direct measurement of the left
      ventricular weight at sacrifice. The mean difference between the two methods was
      9.14 +/- 56.6 mg. The limits of agreement were from -122.4 to +104.1 mg. 4.
      Echocardiography was then used to measure LVM in eight male spontaneously
      hypertensive rats and eight male normotensive Donryu rats at 9 weeks of age. The
      mean LVM of SHR was 768.2 mg +/- 152.6, which was significantly (2P less than
      0.001) greater than the LVM of DRY (435.4 mg +/- 32.2). 5. We conclude that
      echocardiography provides a non-invasive, repeatable and relatively accurate
      estimate of LVM in rats. The method is a potentially useful tool for studying the
      development or regression of cardiac hypertrophy in longitudinal experiments.

PMID- 1387843
TI  - Long-term angiotensin II antagonism in spontaneously hypertensive rats: effects
      on blood pressure and cardiovascular amplifiers.
AB  - 1. The angiotensin II type 1 receptor antagonist, losartan, prevented the
      development of hypertension in spontaneously hypertensive rats (SHR). 2. Losartan
      also prevented the development of left ventricular hypertrophy and vascular
      amplifier abnormalities. 3. Part of the hypotensive effect induced by long-term
      treatment with losartan persisted for a long time after the withdrawal of
      treatment. 4. The results support the hypothesis that angiotensin II contributes
      to the development of hypertension and cardiovascular hypertrophy in SHR.

PMID- 1387845
TI  - The end of an era.

PMID- 1387844
TI  - Open-label study of the safety and efficacy of Fungoid tincture in patients with
      distal subungual onychomycosis of the toes.
AB  - Onychomycosis is the most frequent cause of nail diseases. An open-label study
      has been conducted to evaluate the safety and efficacy of Fungoid Tincture, a
      topical antifungal agent approved by the Food and Drug Administration for the
      treatment of onychomycosis of the toes. Ten patients with culture-proven distal
      subungual onychomycosis were treated twice daily for twelve months with topical
      Fungoid Tincture. Another ten patients with the same condition were treated with
      the vehicle alone. At monthly intervals, the target nail was trimmed, the nail
      bed debrided, and global clinical assessment recorded. After twelve months of
      therapy, all patients applying Fungoid Tincture showed negative findings on
      fungal culture. The vehicle alone benefitted several patients, and may have
      antifungal activity. Adverse effects were minimal, with mild peeling occurring in
      seven patients and erythema noted in one.

PMID- 1387846
TI  - Two directions of dopamine D1/D2 receptor interaction in studies of behavioural
      regulation: a finding generic to four new, selective dopamine D1 receptor
      antagonists.
AB  - A range of new, chemically distinct D1 dopamine receptor antagonists, SCH 39166,
      NO 756, A-69024 and BW 737C, were studied for their effects on behavioural
      responses to the selective D2 agonist RU 24213. Each D1 antagonist not only
      blocked typical sniffing and locomotor responses to RU 24213 but also released
      atypical myoclonic jerking behaviour, while the selective D2 antagonist YM 09151
      blocked these typical responses but did not release jerking. The rank order of
      effectiveness of these D1 antagonists to release such D2 agonist-induced jerking
      was similar to that of their selectivities as D1 antagonists; also, the action of
      BW 737C showed complete enantioselectivity, the inactivity of its R-antipode BW
      736C paralleling enantioselective blockade of D1 but not D2 receptors. It appears
      that while tonic activity through D1 receptors is necessary for the expression of
      typical D2-stimulated behaviour, via well-known cooperative/synergistic D1:D2
      interactions, D1 tone also normally inhibits, via oppositional D1:D2
      interactions, the expression of atypical D2-stimulated behaviours such as
      jerking. Oppositional D1:D2 interactions are evident using all of the classes of
      selective D1 antagonist currently known, and appear to constitute another general
      mode of dopaminergic regulation.

PMID- 1387847
TI  - Hydroxylamine-dependent inhibition of rhodopsin phosphorylation in the isolated
      retina.
AB  - Hydroxylamine (NH2OH), a substance known to accelerate the decay of the
      metarhodopsin II bleaching intermediate of rhodopsin, was examined for its effect
      on the light-dependent phosphorylation of rhodopsin in the intact, isolated
      retina. Groups of ovine and bovine retinas that had been pre-incubated in
      darkness with 32P-inorganic phosphate were supplemented with NH2OH at final
      concentrations of up to 20 mM, then irradiated and further incubated in darkness.
      Rod outer segments isolated from the incubated retinas were subjected to SDS
      PAGE; the gel was analysed for 32P (autoradiography) and protein (Coomassie
      staining), to determine the specific radioactivity (ratio of 32P and protein
      levels; '32P/opsin') of the opsin monomer band. Among retinas of a given
      experimental group, 32P/opsin declined with increasing concentration of added
      NH2OH. The relative value of 32P/opsin exhibited by controls (0 mM NH2OH) was
      halved in the presence of about 1-2 mM NH2OH, and was reduced by greater than or
      equal to 80% in the presence of 20 mM NH2OH. Supplementation of the retina with
      20 mM NH2OH 1 min after irradiation caused relatively little reduction in
      32P/opsin. The results indicate that the light-dependent phosphorylation of
      rhodopsin in situ is substantially inhibited by NH2OH at millimolar levels. The
      data are discussed in relation to previous electrophysiological studies that have
      examined rod dark adaptation in NH2OH-treated retinas.

PMID- 1387848
TI  - Decreased docosahexaenoic acid levels in retina and pigment epithelium of frogs
      fed crickets.
AB  - Whole retina, rod outer segments, and retinal pigment epithelium of frogs (Rana
      pipiens) fed crickets for more than 1 year had significantly lower levels of
      docosahexaenoic acid (22: 6n-3) than the same tissues of frogs fed crickets for
      less than 1 month. Decreases in 22:6n-3 levels in these tissues were compensated
      for by increases in the n-6 polyunsaturated fatty acids (PUFAs), primarily 22:5n
      6. There were no changes in the levels of saturated, monoenoic, or dienoic acids.
      Analysis of diacyl phospholipid molecular species (PLMS) revealed decreases in
      both the 22:6(n-3)-containing dipolyenoic molecular species in
      phosphatidylethanolamine and phosphatidylserine, and the monopolyenoic molecular
      species in phosphatidylcholine. These PLMS were replaced by species containing
      22:5n-6 or other n-6 PUFAs. Examination of fatty acid methyl esters of total
      lipids extracted from crickets revealed that less than 1 mol% fatty acids were of
      the n-3 family, while more than 30 mol% were of the n-6 family. Thus, frogs
      raised on an n-3-deficient diet have reduced levels of n-3 PUFA in their retinas,
      rod outer segments, and retinal pigment epithelium. Although such changes have
      been reported for mammals, this is the first report of the effects of n-3
      deficiency on the lipids of amphibians.

PMID- 1387849
TI  - The effect of growth hormone supplementation on in vitro fertilization outcome: a
      prospective randomized placebo-controlled double-blind study.
AB  - OBJECTIVE: To determine the effect of growth hormone (GH) supplementation to a
      long gonadotropin-releasing hormone agonist (GnRH-a)/human menopausal
      gonadotropin (hMG) treatment protocol, on ovarian response, embryo quality, and
      clinical outcome in in vitro fertilization (IVF). DESIGN: Growth hormone or
      placebo were administered in a prospective randomized double-blind manner.
      PATIENTS: Forty-two normal ovulatory, women who were 38 years of age or less with
      mechanical factor infertility and a normal male factor were selected for this
      study. INTERVENTIONS: Gonadotropin-releasing hormone agonist, 0.5 mg/d, was
      initiated in the midluteal phase of the preceding cycle and continued until the
      day of human chorionic gonadotropin (hCG) administration. Ovulation induction
      with hMG was started 14 days after pituitary down regulation (17 beta-estradiol
      [E2] serum level less than 30 pg/mL). Growth hormone (12 IU/d) or placebo were
      administered on days 1, 3, 5, and 7 of hMG treatment. RESULTS: Breaking the code
      at the completion of the study revealed that 20 women received GH and 22 placebo.
      The age and duration of infertility did not differ between the two groups.
      Follicular phase duration, hMG ampules used, serum E2, and number of follicles
      (greater than or equal to 14 mm) on day of hCG as well as number of oocytes and
      embryos achieved were similar in both groups. Embryo morphology and rate of
      cleavage were also similar. Insulin-like growth factor-I (IGF-I) serum levels did
      not change after pituitary down regulation and increased significantly both after
      GH/hMG and placebo/hMG ovulation induction treatment. Clinical pregnancy rate
      (PR) per embryo transfer and implantation rate were 40% versus 32% and 17.9%
      versus 11.3% in the GH and placebo groups, respectively, and were not
      statistically different. CONCLUSIONS: In normo-ovulatory women undergoing
      ovulation induction for IVF, GH supplementation to hMG after GnRH-a pituitary
      down regulation does not seem to augment ovarian response or improve embryo
      quality. The effect of this regimen on actual PRs and implantation rates needs
      further clarification.

PMID- 1387851
TI  - Laparoscopic treatment of symptomatic diaphragmatic endometriosis: a case report.
AB  - Extreme caution and meticulous surgery are imperative when treating the surface
      of the diaphragm. This procedure should only be performed by an experienced
      laparoscopic surgeon after appropriate consultation with a cardiothoracic
      surgeon. Proper care, a thorough understanding of surrounding anatomic
      structures, and familiarity with laparoscopic instrumentation including the CO2
      laser are required for the safe laser vaporization or excision of any peritoneal
      surface using hydrodissection (7).

PMID- 1387850
TI  - Effects of ethinyl estradiol on semen quality and various hormonal parameters in
      a eugonadal male.
AB  - OBJECTIVE: To determine the influence of estrogens on male fertility. DESIGN: A
      36-year-old eugonadal male was subjected to two different regimens of treatment
      with ethinyl estradiol (EE2). Sperm quality, immunoreactive luteinizing hormone
      (LH) and follicle-stimulating Hormone (FSH), testosterone (T), estrone (E1),
      estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), prolactin (PRL) and sex
      hormone-binding globulin were determined at intervals of 2 weeks for 315 days.
      SETTING: A gender dysphoria clinic. PATIENT: A transsexual male nurse. MAIN
      OUTCOME MEASURES: It was hypothesized (and confirmed) that by comparing the
      effects of increasing and constant dose of EE2 on fertility parameters,
      differences in estrogen-sensitivity would show more clearly. Furthermore, this
      procedure served to find the minimal dose of EE2 for complete testicular
      suppression. RESULTS: Low doses of EE2 (20 micrograms/d) had no negative effect
      on sperm motility and density for a period of approximately 4 weeks, whereas high
      doses (60 micrograms/d) reduced motility already after a few days and led to a
      pronounced decrease in sperm density after 2 weeks. After discontinuation of
      therapy, motility normalized faster than sperm density. Under increasing doses of
      EE2 there was a constant decrease of FSH that occurred several weeks earlier than
      that of LH. Under constant dose of EE2 (60 micrograms/d) the decrease of LH was
      delayed (with respect to FSH) by only a few days. The decrease in T showed a
      stronger correlation with that of FSH than with that of LH. Volume and fructose
      content of the seminal fluid correlated with the decrease in T. Rebound effects
      were observed for FSH, LH, T, and fructose during the therapy-free interval.
      Ethinyl estradiol therapy had no influence on the serum concentrations of E1, E2,
      and PRL. Estrone was the dominant estrogen before and after therapy with EE2.
      Adrenal gland activity was markedly suppressed by EE2, as reflected by the
      decrease in DHEAS. CONCLUSION: The suppressive effect of EE2 on FSH and sperm
      motility was more pronounced and consistent than on LH and sperm density. The T
      decrease appears to be mainly caused by a direct effect of EE2 on the testes.

PMID- 1387852
TI  - Bicornuate nonfused rudimentary uterine horns with functioning endometria and
      complete cervical-vaginal agenesis: magnetic resonance diagnosis.
AB  - A case is reported of a 16-year-old adolescent with cryptomenorrhea. The patient
      had a congenital anomaly of a bicornuate, nonfused, separate rudimentary blind
      uterine horns with functioning endometria, and complete cervical-vaginal
      agenesis. Ultrasound, laparoscopy, and minilaparotomy for unilateral
      salpingectomy failed to accurately identify the exact classification of the
      anomaly. Magnetic resonance imaging, however, accurately correlated with
      operative findings of exploratory laparotomy and McIndoe procedure.

PMID- 1387853
TI  - Adhesive properties of modified glass-ionomer cements.
AB  - The incorporation of water-soluble polymers and/or vinyl monomers into glass
      ionomer cements can yield toughened "hybrid cement-composites". This study
      compared a commercial water-hardening glass-ionomer cement and seven experimental
      hybrids in their bonding to both dentin and Silar composite. The cements were
      sanded and phosphoric-acid-etched or left with an unaltered matrix-formed surface
      when adhesion to composite was tested. The seven hybrids included: 15% 2
      hydroxyethyl methacrylate (HEMA) with appropriate initiators/activators, 29%
      HEMA, 27% HEMA + 0.5% polyacrylic acid (PAA), 0.5% PAA, 1.5% PAA, 2.5% polyvinyl
      alcohol, and 2.5% gelatin. Acceptable bond strengths to applied composite and to
      dentin were observed for most of the modified hybrid cements. There were higher
      bond strengths with composite when the hybrids were left unetched. Bonding of
      some unetched, HEMA-containing cements achieved bond strengths (29% HEMA, 10.09
      MPa) significantly higher than those of the unmodified cement (4.92 MPa). Resin
      modified cements may promote better bonding by improved interaction and
      compatibility with the resin component of the composite.

PMID- 1387854
TI  - Modulus of resilience as predictor for clinical wear of restorative resins.
AB  - Eight posterior restorative resins were tested with respect to flexural strength,
      modulus of elasticity, and modulus of resilience. The mechanical properties were
      correlated to the two-year results of clinical wear tests. Linear relationships
      were found between flexural strength and clinical wear and between modulus of
      resilience and clinical wear. It was concluded that modulus of resilience be used
      in research and quality control for the prediction of clinical wear.

PMID- 1387855
TI  - The use of continuous fiber reinforcement in dentistry.
AB  - Fiber-reinforced composite (FRC) formulations were developed to serve as
      structural components for various dental appliances such as prosthodontic
      frameworks, retainers and splints. Poly(ethylene terephthalate glycol) and
      poly(1,4-cyclohexylene dimethylene terephthalate glycol) reinforced with
      continuous S-2 glass fibers were pultruded into continuous lengths with small
      rectangular cross sections. The microstructure was evaluated with SEM and optical
      microscopy. Fiber content and flexure properties were measured and compared to
      previous results by other authors. The present FRC contained 43-45 volume %
      fiber, which compared favorably with the 5-15 volume % fiber reported by all
      earlier investigators of dental FRC. The present materials achieved 65% of the
      theoretically expected modulus, in contrast to the typical value of 40%
      calculated in the earlier reports. The flexural strength and modulus of the
      experimental FRC were approximately 565 MPa and 20 GPa, respectively. The present
      FRC can be formed into individualized devices, and free fibers need not be
      manipulated by the operator. The improved properties and handling justify further
      study of these FRC as structural dental materials.

PMID- 1387856
TI  - Effects of histamine H2-receptor antagonists and a proton pump inhibitor on the
      mucosal hydroxyproline content of ethanol-HCl-induced gastric lesions in rats.
AB  - We evaluated the effects of different antisecretory agents (H2-receptor
      antagonists and a proton pump inhibitor) on collagen regeneration in rat gastric
      lesions induced by intragastric administration of 50% ethanol +0.15 N HCl (EtOH
      HCl). The lesion indices showed the highest value 30 min after administration of
      EtOH-HCl and a significantly decreased value 15 h later. The mucosal
      hydroxyproline concentration was significantly increased 30 min after EtOH-HCl
      administration, reached a maximum 6 h later and subsequently decreased as time
      passed. Intraperitoneal administration of cimetidine at a dose of 100 mg/kg or
      famotidine at a dose of 5 mg/kg 30 min after EtOH-HCl administration could not
      reduce the lesion indices in less than 24 h and suppressed the increase in
      mucosal hydroxyproline concentrations significantly compared with the control
      group. On the other hand, treatment with 10 mg/kg of E-3810, a proton pump
      inhibitor, had no effects on the lesion healing nor on the fluctuation of mucosal
      hydroxyproline concentrations. These facts suggest that H2-receptor antagonists
      might delay the healing of EtOH-HCl-induced gastric lesions through the
      suppression of collagen regeneration under the condition of exclusion of gastric
      acid secretion.

PMID- 1387857
TI  - Contrasting action of short- and long-term adrenaline infusion on dog skeletal
      muscle glucose metabolism.
AB  - There are important differences between the short- and long-term effects of
      adrenaline on determinants of glucose tolerance. To assess this metabolic
      adaptation at tissue level, the present study examined the effect of acute and
      prolonged in vivo elevation of adrenaline on glycogen metabolism and glycolysis
      in skeletal muscle. Adrenaline (50 ng.kg-1.min-1) was infused for 2 h or 74 h and
      the results compared with 1 h 0.9% NaCl infusion in six trained dogs. Muscle
      glycogen content was reduced by long-term adrenaline (161 +/- 17 vs NaCl 250 +/-
      24 mumol/g dry weight; p less than 0.05) but not short-term adrenaline (233 +/-
      21) indicating a sustained effect of adrenaline on glycogen metabolism. Acutely,
      glycogen synthase I was reduced (short-term adrenaline 12 +/- 6 vs NaCl 22 +/- 7
      mumol glycosyl units.g-1.min-1; p less than 0.05) but returned to normal with
      prolonged adrenaline infusion (20 +/- 5). In contrast, Km for glycogen
      phosphorylase alpha was not changed acutely (short-term adrenaline 31 +/- 6 vs
      NaCl 27 +/- 7 mmol/l inorganic phosphate) but was reduced during long-term
      infusion (19 +/- 4; p less than 0.05 vs short-term adrenaline). Thus, with short-
      and long-term adrenaline infusion, there were different enzyme changes, although
      likely to promote glycogenolysis in both cases. In the glycolytic pathway the
      substrates glucose 6-phosphate and fructose 6-phosphate did not change
      significantly and hexokinase was not inhibited. Acutely, phosphofructokinase had
      reduced Vmax (short-term adrenaline 34 +/- 6 vs NaCl 44 +/- 5 U/g; p less than
      0.05) but was still above the maximal operating rate in vivo.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1387858
TI  - Islet cell metabolism is reflected by the MTT (tetrazolium) colorimetric assay.
AB  - Insulin secretion depends critically on glucose metabolism. We investigated
      whether a rapid viability test could be established for assessing glucose
      metabolism in insulin secreting cells. The MTT (C,N-diphenyl-N'-4,5-dimethyl
      thiazol-2-yl tetrazolium bromide) colorimetric assay (reduction of tetrazolium
      salt to formazan) was applied to rat islets and rat insulinoma cell lines. It was
      found that the rate of formazan production correlated with glucose oxidation and
      glucose utilization at glucose concentrations which also stimulated insulin
      secretion. In differentiated insulinoma INS-1 cells, salt reduction paralleled
      the insulin release at glucose concentrations of up to 8.3 mmol/l. The glucose
      induced formazan production in INS-1 cells and islets was abolished by exposure
      to the Beta-cell cytotoxic agents, streptozotocin or alloxan. The MTT assay thus
      provides a convenient tool for the rapid assessment of Beta-cell metabolism and
      viability.

PMID- 1387859
TI  - Dehydroepiandrosterone: the "missing link" between hyperinsulinemia and
      atherosclerosis?
AB  - A well-established epidemiologic association exists between hyperinsulinemia and
      macrovascular disease. However, the mechanism or mechanisms by which
      hyperinsulinemia promotes atherogenesis is unknown. Recent evidence indicates
      that the adrenal steroid dehydroepiandrosterone (DHEA) exerts multiple
      antiatherogenic effects and also suggests that hyperinsulinemia may reduce serum
      DHEA and DHEA-sulfate levels by decreasing production and enhancing metabolic
      clearance. We advance the hypothesis that hyperinsulinemia promotes macrovascular
      disease in part by reducing serum DHEA and DHEA-sulfate levels and illustrate how
      this may be the case in two clinical conditions characterized by hyperinsulinemic
      insulin resistance: aging and obesity.

PMID- 1387860
TI  - Isolation and partial characterization of a compound with siderophore activity
      from Vibrio parahaemolyticus.
AB  - A compound with siderophore activity was purified by successive column and thin
      layer chromatographic procedures from Dowex 1 x 8 extracts of culture
      supernatants of Vibrio parahaemolyticus AQ 3354. The strain synthesized the
      compound in culture media containing less than 2 microM added FeCl3. Hydrolysis
      of the compound yielded alanine, ethanolamine, citric acid and 2-ketoglutaric
      acid. The 1H-NMR spectrum exhibited the presence of a residue from each of these
      components in the intact molecule. The fast-atom bombardment mass spectrum of the
      methyl ester derivative indicated a prominent ion at m/z 477, probably
      corresponding to [M + 1] ion. Other strains of V. parahaemolyticus were also
      found to produce this compound when grown in an iron-limited medium.

PMID- 1387861
TI  - Rhizoferrin: a complexone type siderophore of the Mucorales and entomophthorales
      (Zygomycetes).
AB  - The present investigation presents evidence that rhizoferrin, a novel
      polycarboxylate or complexone-type siderophore, originally isolated from Rhizopus
      microsporus, represents the common siderophore within the Zygomycetes. Thus,
      rhizoferrin could be detected by HPLC analysis in various families of the
      Mucorales, e.g., Rhizopus microsporus var. rhizopodiformis, Mucor mucedo and
      Phycomyces nitens (Mucoraceae), Chaetostylum fresenii and Cokeromyces recurvatus
      (Thamnidiaceae), Cunninghamella elegans and Mycotypha africana (Choanephoraceae)
      and Mortierella vinacea (Mortierellaceae) and in Basidiobolus microsporus
      (Entomophthorales). The function of rhizoferrin as a siderophore in the fungus R.
      microsporus var. rhizopodiformis was demonstrated by time- and concentration
      dependent uptake of [55Fe]-labelled rhizoferrin, yielding saturation kinetics
      with values of Km = 8 microM and V(max) = 1.2 nmol min-1 (mg dry wt)-1.

PMID- 1387862
TI  - Specificity and sensitivity of hexosaminidase assays and DNA analysis for the
      detection of Tay-Sachs disease gene carriers among Ashkenazic Jews.
AB  - Tay-Sachs disease (TSD), a neurodegenerative disorder resulting from a deficiency
      of the lysosomal enzyme hexosaminidase A (HexA), clusters in Ashkenazic Jews.
      Population-based screening programs to detect carriers of TSD genes by means of
      HexA assays have been active since the 1970s. The recent characterization of 3
      mutations in the HEXA gene (in exon 7, exon 11, and intron 12), which account for
      over 90% of HEXA mutations in Ashkenazim, appeared to offer better options for
      screening and diagnosis. The relative frequencies of the three mutations in
      Montreal are similar to those reported in four other North American populations.
      We compared enzyme and DNA analyses to determine specificity and sensitivity of
      each test when the other was used as the confirmatory procedure. Neither
      procedure has a sensitivity of 1.0. Maximum sensitivity and specificity were
      achieved by using both tests together. The findings here are likely to apply to
      most cases where the variant screened enzyme phenotype can result from more than
      one mutation.

PMID- 1387863
TI  - Coagulopathy in disseminated intravascular coagulation due to abdominal sepsis:
      determination of prothrombin fragment 1 + 2 and other markers.
AB  - To estimate the degree of coagulopathy in abdominal sepsis, we measured the
      plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III
      complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PIC) by the enzyme
      linked immunosorbent assay in 38 patients with disseminated intravascular
      coagulation (DIC). In 20 patients with DIC due to abdominal sepsis, plasma levels
      of F1 + 2, TAT and PIC were 2.6 nmol/l, 27.9 micrograms/l and 1.5 micrograms/ml,
      respectively, with a mean antithrombin III (AT III) activity of 41.7%. F1 + 2,
      TAT, PIC and AT III levels were 4.7 nmol/l, 75.8 micrograms/l, 8.8 micrograms/ml
      and 70.9% in 18 patients with DIC as the result of malignancy. Though AT III
      levels in DIC due to sepsis were lower than those in DIC due to malignancy, the
      levels of F1 + 2, TAT and PIC in the former were not significantly more increased
      than those in the latter. The plasma levels of F1 + 2 were positively correlated
      with TAT and PIC in DIC patients with malignancy; however, there was no
      correlation between F1 + 2 and TAT or PIC in DIC patients with sepsis. In
      addition, the levels of serum albumin in the two groups were similar. These
      results suggest that activation of coagulation and fibrinolytic systems may not
      be so prominent in cases of DIC due to abdominal sepsis, compared to related
      events in DIC due to malignancy. It is also suggested that the depletion of AT
      III in cases of sepsis is not only caused by a consumption related to
      intravascular coagulation or to an alternate distribution of protein.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1387864
TI  - [Severe disability. Part 2: The difficult comparison with same age probands].
AB  - With their texts on Schwerpflegebedurftigkeit, the legislators have set the
      interpreters of legal texts a difficult task. In practice, attempts by the
      "users" of such texts to find solutions inexorably lead to aporias. Responsible
      for decision-taking is the health insurance carrier, with the physician
      exclusively acting as a counsellor on the medical aspects. The advised
      comparisons with persons of identical age with the intention of establishing
      Schwerpflegebedurftigkeit is not required by the legislator, and it is not easy
      to see what sense it is supposed to make. The corresponding guidelines drawn up
      by the leading associations are not unequivocal and are therefore open to
      misunderstanding.

PMID- 1387865
TI  - Nutritional alterations in persons with HIV infection.
AB  - Potential relationships among nutritional status, immune function and quality of
      life were examined in a convenience sample of 40 outpatient homosexual and
      bisexual males stratified into five categories, using modified Walter Reed
      Staging Criteria. Nutritional status was assessed by measuring height, weight,
      triceps skinfold thickness, arm circumference, nutrient intake and serum albumin.
      Immune status was evaluated by determining T-helper cell numbers and percentages.
      The Quality of Life test was used to obtain information about life quality.
      Nutritional assessment failed to show significant differences among groups with
      the exception that serum albumin levels were reduced in persons with AIDS. The
      significance of change in serum albumin in regard to nutritional status is
      unclear, since serum albumin is affected by a number of non-nutritional factors,
      such as hydration status and liver function. The study also revealed a
      significant decline in T-helper percentages, but not absolute T-helper cell
      numbers as a function of disease stage. There were no statistically significant
      differences between the quality of life scores with respect to each grouping.
      These data suggest that asymptomatic patients as well as those with ARC or stable
      AIDS are able to maintain body weight and composition.

PMID- 1387867
TI  - In vitro endothelialization of carbon-coated Dacron vascular grafts.
AB  - Physical vapour deposition is used to coat vascular prostheses with pyrolytic
      carbon. This coating may facilitate the development of an endothelial monolayer
      in grafts implanted in laboratory animals. This in vitro study compared the
      adherence and growth of cultured porcine aortic endothelial cells (EC) seeded in
      vitro on carbon-coated Dacron, to uncoated prostheses. The cells were incubated
      at 5 x 10(4) cells/cm2. Progress was monitored at different times (TO + 2 hours,
      D 1, D 4, D 8) by microscopic observation, when cell counts were made; and by
      scanning electronic microscopy (SEM) to evaluate morphological EC-graft
      interactions. Cell adherence was independent of the carbon coating but cellular
      growth occurred only on carbon-coated Dacron. The SEM observations showed both
      the shape of the adherent cells, which were rounded on uncoated Dacron and
      extensively spread on carbon-coated prostheses, and the morphology of the carbon
      coating.

PMID- 1387868
TI  - The human squamous cervical carcinoma cell line, HOG-1, is responsive to steroid
      hormones.
AB  - Growth of the human squamous cervical carcinoma cell line, HOG-I, was stimulated
      in response to oestradiol in serum-containing and chemically defined medium. The
      oestradiol-stimulated growth could be inhibited by 4-OH tamoxifen, progesterone
      and medroxyprogesterone acetate; the last 2 compounds also inhibited basal cell
      growth in serum-containing and chemically defined media. The data are consistent
      with the sensitivity of human squamous cervical cancer to sex-steroid hormones
      and suggest that endocrine therapies may be of benefit in this disease.

PMID- 1387869
TI  - Deoxyspergualin, a novel immunosuppressant, markedly inhibits human mixed
      lymphocyte reaction and cytotoxic T-lymphocyte activity in vitro.
AB  - Deoxyspergualin (DSG) has demonstrated potent immunosuppressive activities in
      vivo. However, because of its lability in culture medium, the mechanism of
      activity has not yet been identified in vitro. In this study, a more stable
      analogue, deoxymethylspergualin (MeDSG), was used to investigate the in vitro
      immunosuppressive activity of DSG. MeDSG suppressed both human mixed lymphocyte
      reaction (MLR) and cytotoxic T-lymphocyte (CTL) activity at doses greater than
      0.1 micrograms/ml in vitro. In kinetics studies, MeDSG was found to suppress a
      MLR when added on day 3 of a 7 day MLR incubation but cyclosporin A (CYA)
      suppressed a MLR only when added during the initial stage of a MLR (i.e. on day
      1). In studies of cell surface phenotype in the MLR, MeDSG treatment decreased
      the numbers of CD8+ lymphocytes but those of CD4+ lymphocytes were not affected.
      In addition, MeDSG had no significant effect on interleukin-2 (IL-2) receptor
      expression or IL-2 production. These results suggest that MeDSG suppresses the T
      cells which are proliferating competent cells such as cytotoxic T-cells (CD8+),
      but has a different mode of immunosuppressive action compared with CYA.

PMID- 1387866
TI  - Chronic liver disease rarely follows acute hepatitis B in non-immunocompromised
      adults.
AB  - The risk of developing a chronic carriage state after acute hepatitis B infection
      in adults was evaluated. Two hundred and eighty-nine HBV-susceptible heterosexual
      partners of acute hepatitis B patients were used to investigate the effectiveness
      of post-exposure immunoprophylaxis; 75 of them received hepatitis B vaccine, 72
      hepatitis B hyperimmune globulin (HBIG), 71 vaccine plus HBIG and 71 placebo.
      Participants were interviewed, clinically examined and serum specimens were taken
      at 1, 3, 6 and 9 months after their first intervention. Serum samples were tested
      for ALT and HBV markers (HBsAg, anti-HBc and anti-HBs) using radio immunoassays.
      Forty-six (15.9%) of the heterosexual partners examined were infected; the
      incidence of HBV infections was higher among placebo (18.3%, 13/71) and HBIG
      (18.1%, 13/72) recipients compared to vaccine (16.0%, 12/75) and HBIG plus
      vaccine (11.3%, 8/71) recipients, but the differences were not statistically
      significant. Infections were significantly more often subclinical after
      immunoprophylaxis (p = 0.03). HBsAg was detected in all eight clinical and in 13
      of the 38 subclinical cases. In the remaining 25 subclinical cases HBV infections
      were diagnosed by the development of anti-HBc and anti-HBs during the follow-up
      period. Finally, all 46 cases studied cleared the HBsAg.

PMID- 1387870
TI  - Effects of a diet regimen on pituitary and steroid hormones in male ice hockey
      players.
AB  - Serum concentrations of androgens, cortisol, androgen binding proteins, pituitary
      hormones, together with anthropometric variables and sports performance were
      studied in two different elite male ice hockey teams. One of the teams (DIF, n =
      22) participated in a special dietary program including reduction in fat from
      approximately 40 per cent of total energy intake (E%) to less than 30 E% and an
      increase in carbohydrate intake from 45 E% to about 55 E%, while the other (SSK,
      n = 21) served as a control group and had no special dietary program. The study
      covered a 7-month period. Basal values of serum testosterone, sex hormone binding
      globulin (SHBG), non-SHBG-bound testosterone (NST), cortisol,
      dehydroepiandrosterone sulfate (DHAS) and LH did not differ between the two
      teams. Serum concentrations of testosterone, SHBG, NST and cortisol increased
      significantly during the study period in the DIF group and were, with the
      exception of SHBG, significantly higher than in the SSK group at the end of the
      study (33.0 vs 26.8 nmol/l, p less than 0.05; 22.5 vs 18.3 nmol/l, p less than
      0.05; and 548 vs 464 nmol/l, p less than 0.01). The ratio between NST and
      cortisol which was used as an index of anabolic/catabolic steroid balance did not
      change in either group during the study. A significant decrease in the serum
      concentrations of LH during the observation period was found in the SSK group.
      The endocrine differences between the teams may be explained by a relative
      negative energy balance in DIF, together with a reduced fat and increased
      carbohydrate intake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387871
TI  - The relationship between age and the prevalence of senile dementia: a meta
      analysis of recent data.
AB  - A linear regression model derived from a meta-analysis of 13 epidemiological
      studies of senile dementia conducted since 1980, and employing internationally
      known case-finding procedures, suggests a much lower general rate of dementia
      prevalence than has been previously estimated. An exponential increase with age
      is observed, with senile dementia prevalence diagnosed by Diagnostic and
      Statistical Manual (DSM-III) criteria doubling every 6 years and senile dementia
      of the Alzheimer's type (SDAT) every 4.2 years. Studies providing data for the
      oldest ages indicating a drop in the rate of increase after the age of 80 suggest
      that senile dementia may be age-related rather than ageing-related. Estimates
      derived from this model may provide a reasonably accurate means of estimating
      dementia prevalence in the general population. The limitations of this method for
      the purposes of prediction and studies of risk factors are discussed in relation
      to the hypothesized heterogeneity of senile dementia and possible cohort effects.

PMID- 1387873
TI  - [Demonstration of soluble IgG-Fc type II receptors (or s-Fc-gamma-II-R) in human
      whole saliva].
AB  - Twenty human salivary samples from two groups of patients (with or without dental
      caries) were tested for the presence of soluble forms of Fc gamma receptors type
      II (sFc gamma RII): sFc gamma RII were detected by immunoblotting using a
      radiolabelled monoclonal antibody directed against human Fc gamma RII. These
      soluble forms specifically interact with the Fc portion of IgG and are produced
      by cells of the immune system (macrophages, neutrophils, Langerhans cells). This
      study showed that sFc gamma RII are present in human unstimulated saliva. The
      statistical analysis indicated that the relative amounts of sFc gamma RII in
      human unstimulated saliva are variable depending on the patient. No apparent
      association was found between the sFc gamma RII and the oral status of the
      patients.

PMID- 1387872
TI  - Tumor diagnosis by PET: potential of seven tracers examined in five experimental
      tumors including an artificial metastasis model.
AB  - The potential of seven tracers for the metabolic imaging of tumors by positron
      emission tomography was studied using five experimental tumor models. The tracers
      examined were 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), 2-deoxy-2-[18F]fluoro-D
      galactose (2-[18F]FdGal) and 2-deoxy-2-[18F]fluoro-L-fucose (2-[18F]FdFuc) for
      investigating energy metabolism. L-[methyl-11C]Methionine ([11C]Met) and 6
      [18F]fluoro-L-fucose (6-[18F]FFuc) were used for assessing protein and
      glycoprotein synthesis, while [3H]thymidine ([3H]Thd) and 2-deoxy-5'
      [18F]fluorouridine ([18F]FdUrd) were used to investigate nucleic acid metabolism.
      The highest mean uptake by the five different tumors was found for [3H]Thd,
      followed in order by [18F]FDG, [11C]Met, 2-[18F]FdGal, [18F]FdUrd, 2-[18F]FdFuc
      and 6-[18F]FFuc. The tumor-to-tissue uptake ratios indicated that the
      nucleosides, [11C]Met and 6-[18F]FFuc were better tracers in the brain region.
      All the tracers except for the fucose analogs were suitable for the thoracic
      region, while [11C]Thd and [18F]FDG were superior in the abdominal region. In
      comparison with the primary tumor model of Lewis lung carcinoma (3LL), [3H]Thd
      uptake in the artificial metastatic 3LL model showed the maximum enhancement,
      followed by [18F]FDG, [11C]Met and the other tracers. The [18F]FDG uptake
      correlated with the [3H]Thd uptake. [18F]FdUrd, 6-[18F]FFuc and 2-[18F]FdGal
      could be used for distinguishing different types of tumors. The combined use of
      these radiotracers can possibly allow the assessment of tumor metabolism, and
      this indicates the viability of tumors.

PMID- 1387874
TI  - Cytoplasmic dynein participates in the centrosomal localization of the Golgi
      complex.
AB  - The localization of the Golgi complex depends upon the integrity of the
      microtubule apparatus. At interphase, the Golgi has a restricted pericentriolar
      localization. During mitosis, it fragments into small vesicles that are dispersed
      throughout the cytoplasm until telophase, when they again coalesce near the
      centrosome. These observations have suggested that the Golgi complex utilizes a
      dynein-like motor to mediate its transport from the cell periphery towards the
      minus ends of microtubules, located at the centrosome. We utilized semi-intact
      cells to study the interaction of the Golgi complex with the microtubule
      apparatus. We show here that Golgi complexes can enter semi-intact cells and
      associate stably with cytoplasmic constituents. Stable association, termed here
      "Golgi capture," requires ATP hydrolysis and intact microtubules, and occurs
      maximally at physiological temperature in the presence of added cytosolic
      proteins. Once translocated into the semi-intact cell cytoplasm, exogenous Golgi
      complexes display a distribution similar to endogenous Golgi complexes, near the
      microtubule-organizing center. The process of Golgi capture requires cytoplasmic
      tubulin, and is abolished if cytoplasmic dynein is immunodepleted from the
      cytosol. Cytoplasmic dynein, prepared from CHO cell cytosol, restores Golgi
      capture activity to reactions carried out with dynein immuno-depleted cytosol.
      These results indicate that cytoplasmic dynein can interact with isolated Golgi
      complexes, and participate in their accumulation near the centrosomes of semi
      intact, recipient cells. Thus, cytoplasmic dynein appears to play a role in
      determining the subcellular localization of the Golgi complex.

PMID- 1387876
TI  - Phorbol ester-induced promyelocytic leukemia cell adhesion to marrow stromal
      cells involves fibronectin specific alpha 5 beta 1 integrin receptors.
AB  - The human promyelocytic cell line NB4 exhibited a weak adhesion capacity for bone
      marrow-derived stromal cells and their extracellular matrices (5-15% of adherent
      cells). Adhesion was enhanced by pulse-treatment of cells with phorbolester (PMA
      10(-7) M). Adhesion was induced within minutes, was fibronectin-specific, and
      affected up to 100% of the treated cells. This biological response to PMA
      resulted from the activation of protein kinase C (PKC), since PKC inhibitors
      (staurosporine, sphingosine, CGP 41251, and calphostin C) prevented the
      phenomenon. Phenotypical analysis of integrin receptor expression (particularly
      FN receptors VLA-4 and VLA-5) at the membrane of untreated or PMA-treated cells
      revealed that PMA induced no significant modification of the level of expression
      of these receptors. However, inhibition studies carried out with anti-VLA
      monoclonal antibodies demonstrated that the FN-specific adhesion triggered by PKC
      involved the alpha 5 beta 1 FN-specific receptors (VLA-5). We showed that the
      binding of NB4 cells to fibronectin was RGD-dependent. PMA-induced adhesion was
      not correlated to phosphorylation of the VLA-5 receptor. These findings may
      partially explain the malignant behaviour of these cells: The loss of their
      capacity to adhere to stromal cells may arrest differentiation and explain the
      large number of leukemic cells in the circulation.

PMID- 1387877
TI  - Cytoplasmic accumulation of cyclin B1 in human cells: association with a
      detergent-resistant compartment and with the centrosome.
AB  - Mitotic cyclins are thought to function as key regulatory subunits of the
      universal M-phase-promoting p34cdc2 protein kinase. Previous immunolocalization
      studies have demonstrated that a fraction of p34cdc2 undergoes cell cycle
      dependent accumulation at the centrosome during G2/M. In order to identify the
      mitotic cyclins with which this p34cdc2 fraction interacts, we carefully examined
      the subcellular distribution of both cyclin A and B1 in HeLa cells. We show here
      that part of cyclin B1 is associated with duplicating centrosomes throughout its
      accumulation in the cytoplasm and up to metaphase. In contrast cyclin A does not
      exhibit centrosomal association except at the onset of mitosis, from preprophase
      up to metaphase. We also present cytological and biochemical evidence that cyclin
      B1 is preferentially accumulated as a detergent-insoluble protein independently
      of the state of microtubule assembly and under experimental conditions where most
      of p34cdc2 is soluble. Interestingly, the electrophoretic pattern of the minor
      insoluble p34cdc2 fraction was previously shown to be particularly enriched in
      slow-migrating and presumably hyperphosphorylated isoforms, known to interact
      specifically with cyclin B1 during interphase. From these results we propose that
      the interaction of cyclin B1 with the centrosomes and with the cytoplasmic
      structures is a constitutive feature of the mechanism whereby a fraction of
      p34cdc2 is recruited and subsequently targeted to the cyclin B-dependent
      activation pathway.

PMID- 1387875
TI  - The inner dynein arms I2 interact with a "dynein regulatory complex" in
      Chlamydomonas flagella.
AB  - We provide indirect evidence that six axonemal proteins here referred to as
      "dynein regulatory complex" (drc) are located in close proximity with the inner
      dynein arms I2 and I3. Subsets of drc subunits are missing from five second-site
      suppressors, pf2, pf3, suppf3, suppf4, and suppf5, that restore flagellar
      motility but not radial spoke structure of radial spoke mutants. The absence of
      drc components is correlated with a deficiency of all four heavy chains of inner
      arms I2 and I3 from axonemes of suppressors pf2, pf3, suppf3, and suppf5.
      Similarly, inner arm subunits actin, p28, and caltractin/centrin, or subsets of
      them, are deficient in pf2, pf3, and suppf5. Recombinant strains carrying one of
      the mutations pf2, pf3, or suppf5 and the inner arm mutation ida4 are more
      defective for I2 inner arm heavy chains than the parent strains. This evidence
      indicates that at least one subunit of the drc affects the assembly of and
      interacts with the inner arms I2.

PMID- 1387878
TI  - Distribution of cytoplasmic and axonemal dyneins in rat tissues.
AB  - Microtubule-associated protein 1C (MAP 1C) is now defined as brain cytoplasmic
      dynein. Recent studies have suggested that cytoplasmic dynein is a motor protein
      responsible for the intracellular microtubule-based motility in neuronal and non
      neuronal cells. We have prepared an antibody against bovine brain MAP 1C and have
      examined the localizations of cytoplasmic dynein in rat tissues. Immunoblots of
      extracts from the tissues showed that the dynein was present in brain, testis,
      liver, kidney and lung. Immunohistochemical experiments have demonstrated that
      dynein is localized in Purkinje cells of cerebellum and axons of central and
      peripheral nervous systems. In non-neuronal tissues, the antibody staining was
      intense in many types of cells, such as hepatocytes, epithelia of renal
      convoluted tubules, secretory cells of adrenal medulla and spermatids. Glomeruli
      of kidney, bronchial epithelia and type II pneumocytes of lung, pancreatic islets
      and acini, adrenal cortex and Sertoli cells were moderately positive upon
      exposure to the cytoplasmic dynein antibody. On the other hand, the localization
      of axonemal dynein was examined using antibodies against flagellar dynein of sea
      urchin spermatozoa. Anti-axonemal dynein labeled cilia and flagella in rat
      tissues whereas anti-MAP 1C did not stain axonemes. We also tested for
      immunological cross-reactivity between cytoplasmic and axonemal dyneins to probe
      for molecular similarities. Anti-axonemal dynein reacted with MAP 1C weakly.
      These results have confirmed that cytoplasmic dyneins are distributed widely
      among rat organs, not only in neuronal but also in non-neuronal tissues. There is
      no similarity in the localization of cytoplasmic and axonemal dyneins but there
      is some similarity in molecular antigenicity.

PMID- 1387879
TI  - Cyanosis and left ventricular hypertrophy.

PMID- 1387880
TI  - Implications of ultrasonically diagnosed polycystic ovaries. II. Studies of
      dynamic and pulsatile hormonal patterns.
AB  - Studies of 6-h hormone pulse patterns distinguished patients with polycystic
      ovarian disease (PCOD) from those with hyperprolactinaemia or hypothyroidism
      associated with ultrasonically diagnosed polycystic ovaries (PCO). No specific
      derangement in the gonadotrophin pulse pattern was responsible for these changes,
      as shown in patients with and without PCO in the latter two groups. These changes
      may reflect an abnormal ovarian response to normal or abnormal gonadotrophic
      drive. Out of 26 patients with PCO and elevated dehydroepiandrosterone sulphate
      (DHEA-S) levels, only three patients (11.5%) proved to have adrenal 21
      hydroxylase deficiency. Ultrasonic visualization of polycystic ovaries must be
      supplemented with an endocrine biochemical assessment. Moreover, mild elevation
      of DHEA-S, without a concurrently high 17 alpha-hydroxyprogesterone level was not
      diagnostic of adrenal hyperplasia.

PMID- 1387882
TI  - Fertility following laparoscopic management of benign adnexal cysts.
AB  - Fertility following laparoscopic treatment of benign adnexal cysts without
      ovarian suture was studied retrospectively. Patients with endometriomas or who
      were previously infertile were excluded. Thirty-eight patients treated
      conservatively were included, 10 after partial resection of functional cysts, 23
      after an ovarian cystectomy and six after treatment of a paraovarian cyst. One
      patient had two cysts. The overall intrauterine pregnancy rate was 92%; one
      patient had an ectopic pregnancy (2.6%). From these results, we conclude that
      fertility following laparoscopic treatment of adnexal cysts appears to be normal.
      Technical guidelines to improve laparoscopic cystectomy are proposed.

PMID- 1387881
TI  - Do analogues of gonadotrophin releasing hormone influence follicular fluid
      steroid levels, oocyte maturity and fertilization rates?
AB  - One-hundred-and-twelve samples of follicular fluid from 32 patients undergoing in
      vitro fertilization and embryo transfer were analysed in this study. The
      follicular fluids were analysed for any relationships between oestradiol,
      progesterone and 17 alpha-hydroxyprogesterone levels, the progesterone/oestradiol
      and 17 alpha-hydroxyprogesterone/oestradiol ratios and oocyte maturity and
      fertilization rates. In Group A, consisting of women who used analogues of
      gonadotrophin-releasing hormone during ovarian stimulation with human menopausal
      gonadotrophin, the progesterone/oestradiol ratio rose in parallel with the
      fertilization rate (P less than 0.05). Group B comprised patients treated with
      human menopausal gonadotrophin alone. No significant relationship was found
      between the other parameters, oocyte maturation and fertilization rates in either
      group.

PMID- 1387883
TI  - Cell retargeting by bispecific monoclonal antibodies. Evidence of bypass of
      intratumor susceptibility to cell lysis in human melanoma.
AB  - Intratumor heterogeneity for susceptibility to cytotoxic T lymphocytes (CTL)
      mediated lysis represents a major obstacle to cancer adoptive immunotherapy. To
      overcome the heterogeneity observed in terms of susceptibility of target cells to
      cell-mediated lysis, in this study we used two purified bispecific monoclonal
      antibodies (bsmAbs) that recognize molecules expressed by cytotoxic effector
      cells (CD3 and IgG Fc receptorial molecules), as well as one high molecular
      weight melanoma-associated antigen (HMW-MAA). The ability of these reagents to
      enhance or induce a relevant in vitro cytotoxic activity by a CTL clone (CTL 49)
      isolated from PBL of a melanoma patient was tested on a large panel of autologous
      and allogeneic melanoma cell lines and clones. Functional studies revealed that
      the CTL 49 clone lysed all the HMW-MAA+ tumor lines in the presence of bsmAbs and
      that these reagents affected the target lysis in a cooperative fashion. The
      effectiveness of bsmAbs in overcoming the heterogeneous susceptibility of human
      melanoma cells to cell-mediated lysis may find practical implications in cancer
      adoptive immunotherapy.

PMID- 1387884
TI  - Transfection of a glycosylated phosphatidylinositol-anchored folate-binding
      protein complementary DNA provides cells with the ability to survive in low
      folate medium.
AB  - KB cells express a folate-binding protein that is anchored to the plasma membrane
      by a glycosylated phosphatidylinositol (GPI) tail and these cells can grow in
      medium containing a very low folate concentration (1 nM). In contrast, mouse 3T3
      cells do not express a membrane-associated folate-binding protein and cannot grow
      under similar low folate conditions. In these studies, 3T3 cells were transfected
      with a vector containing the cDNA that codes for the KB cell folate-binding
      protein. In contrast to the wild-type 3T3 cells, the transfected 3T3 cells
      express a level of folate-binding protein similar to KB cells, 1 and 1.4
      ng/micrograms protein, respectively. The capacity for binding [3H] folate to the
      surface of transfected 3T3 cells cultured in folate-deficient medium is 7.7
      pmol/10(6) cells, and this is approximately 50% of the surface binding capacity
      of KG cells under similar culture conditions. Moreover, after treatment of the
      transfected 3T3 cells with phospholipase C specific for phosphatidylinositol, the
      binding of [3H] folate to the surface of these cells is reduced by 90%,
      indicating that, like the KB cells, the folate-binding protein is anchored to the
      plasma membrane by a GPI tail. Although the doubling time of wild-type 3T3 cells
      markedly increases after 13 d of culture in folate-deficient medium, the doubling
      time of both the transfected 3T3 cells and KB cells do not change. The results of
      these experiments indicate that the GPI-anchored folate-binding protein provides
      a mechanism to maintain a level of folate that permits the folate-dependent
      metabolic functions necessary for cell survival under low folate conditions.

PMID- 1387885
TI  - Live Borrelia burgdorferi preferentially activate interleukin-1 beta gene
      expression and protein synthesis over the interleukin-1 receptor antagonist.
AB  - Lyme arthritis is one of the few forms of chronic arthritis in which the cause is
      known with certainty. Because cytokines are thought to contribute to the
      pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease
      spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1
      beta and the IL-1 receptor antagonist (IL-1ra) in human peripheral blood
      mononuclear cells. Live B. burgdorferi induced fivefold more IL-1 beta than IL-1
      alpha and sevenfold more IL-1 beta than IL-1ra; LPS or sonicated B. burgdorferi
      induced similar amounts of all three cytokines. This preferential induction of IL
      1 beta was most dramatic in response to a low passage, virulent preparation of B.
      burgdorferi vs. three high passage avirulent strains. No difference in induction
      of IL-1ra was seen between these strains. The marked induction of IL-1 beta was
      partially diminished by heat-treatment and abrogated by sonication; IL-1ra was
      not affected. This suggested that a membrane component(s) accounted for the
      preferential induction of IL-1 beta. However, recombinant outer surface protein
      beta induced little IL-1 beta. By 4 h after stimulation, B. burgdorferi induced
      sixfold more IL-1 beta protein than LPS. In contrast to LPS-induced IL-1 beta
      mRNA which reached maximal accumulation after 3 h, B. burgdorferi-induced IL-1
      beta mRNA showed biphasic elevations at 3 and 18 h. B. burgdorferi-induced IL-1ra
      mRNA peaked at 12 h, whereas LPS-induced IL-1ra mRNA peaked at 9 h. IL-1 beta
      synthesis increased in response to increasing numbers of spirochetes, whereas IL
      1ra synthesis did not. The preferential induction by B. burgdorferi of IL-1 beta
      over IL-1ra is an example of excess agonist over antagonist synthesis induced by
      a microbial pathogen, and may contribute to the destructive lesion of Lyme
      arthritis.

PMID- 1387886
TI  - Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and
      balloon-dilated atherosclerotic arteries.
AB  - The possibility of using an exclusively percutaneous strategy to deliver foreign
      DNA to normal and balloon-dilated atherosclerotic arteries was studied by
      analysis of transfection efficiency in a rabbit model. A total of 22 external
      iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were
      transfected with a solution of luciferase expression vector plasmid and liposome,
      using a dual balloon-catheter system. Analysis of the transfected segments
      revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12
      balloon-injured atherosclerotic, P = NS); no activity could be detected in the
      contralateral limb arterial segments used as controls. Luciferase activity levels
      in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner
      light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU
      in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of
      successfully transfected atherosclerotic sections showed expression of the
      luciferase gene mRNA from rare cells (less than 1/1,000) limited to the
      neointimal lesion. Thus, expression of new genetic material may be achieved in
      both normal and balloon-dilated atherosclerotic arteries following an exclusively
      percutaneous approach. The low efficiency of the current delivery strategy,
      however, represents a potential limitation that must be improved if this strategy
      is to be applied as a therapeutic approach to human vascular disease.

PMID- 1387887
TI  - Interphotoreceptor matrix in the human retina: cone-like domains surround a small
      population of rod photoreceptors.
AB  - The interphotoreceptor matrix (IPM) in mammalian retinas is subdivided into rod
      and cone specific compartments: peanut agglutinin (PNA) binding glycoconjugates
      are associated with cones, whereas wheat germ agglutinin (WGA) binding
      glycoconjugates are associated with rods. To establish the identity of a
      photoreceptor cell type in the human retina with rod dimensions but with a matrix
      domain which stains with PNA, double label studies, using PNA-ferritin to
      decorate the extracellular domains and immunocytochemical techniques using a rod
      specific anti-opsin antibody were conducted. The PNA-binding domains were
      observed in the cone-associated IPM as well as in the IPM surrounding a small
      population of rod-shaped photoreceptors. The outer segments of these rod-shaped
      photoreceptors showed intense labeling with a rod specific anti-opsin antibody as
      did all other rods which were free of PNA-labeling. A quantitative analysis of
      all retinal quadrants indicates that this novel rod represents approximately 0.3%
      of the total rod population in the human retina.

PMID- 1387888
TI  - Influence of size of regions of interest on PET evaluation of caudate glucose
      consumption.
AB  - The aim of this study was to analyze the influence of variations in the size of
      regions of interest (ROIs) on values of caudate glucose consumption [regional
      cerebral metabolic rate of glucose (rCMRglc)] assessed by PET. In addition, we
      tried to establish the influence of ROI size on levels of significance assessing
      differences in mean caudate glucose consumption between two groups of subjects.
      For this purpose, rCMRglc was measured using [18F]fluorodeoxyglucose and the PC
      4096 PET camera with an in-plane resolution of 7.1 mm in 12 normal subjects and
      12 subjects with early Huntington disease. Caudate rCMRglc was histographically
      determined using 10 different ROI widths ranging from 2 mm, corresponding to the
      peak value of caudate rCM-Rglc, to 20 mm. The increase in ROI width from 2 to 20
      mm led to a significant decrease of caudate rCMRglc by approximately 66% in the
      normal subjects and in the patients. The Student t value assessing the
      differences in mean caudate rCMRglc between the two groups decreased gradually
      from 5.61 for an ROI width of 2 mm to 3.78 for an ROI width of 20 mm. This
      corresponds to a worsening of the level of significance from 10(-5) to 10(-3),
      i.e., by a factor of 100. These data show that (given the resolution of presently
      used PET cameras) the selection of peak values of caudate rCMRglc is the best way
      to discriminate between groups of subjects supposed to differ with respect to
      caudate rCMRglc.

PMID- 1387889
TI  - Radiocontrast-induced nephropathy: current status and future prospects.
AB  - Radiocontrast-induced nephropathy (RCIN), a leading cause of in-hospital acute
      renal failure, is an acute decrease in renal function related to intravascular
      administration of iodinated radiocontrast agents. Though RCIN is relatively
      uncommon in patients without predisposing factors, patients with preexisting
      renal dysfunction, diabetes mellitus and severe congestive heart failure are at
      increased risk for acute renal failure following radiocontrast. Three recently
      developed animal models have provided important insights into the pathophysiology
      of RCIN. Specifically, these studies have implicated transient renal ischemia,
      direct renal tubular toxicity and changes in glomerular capillary permeability as
      possible mediators of RCIN, and these pathophysiologic mechanisms are not
      mutually exclusive. There is currently no effective treatment for RCIN. Assuring
      adequate hydration may reduce the risk of RCIN. In addition, synthetic atrial
      natriuretic factor and/or mannitol are promising, but as yet unproven, approaches
      to the prophylaxis of RCIN.

PMID- 1387891
TI  - TNF in combination with GM-CSF enhances the differentiation of neonatal cord
      blood stem cells into dendritic cells and macrophages.
AB  - We describe dendritic cell progenitors within the CD34+ stem cell compartment in
      neonatal cord blood and identify growth factors contributing to their
      differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF),
      although mainly promoting the growth and differentiation of monocyte-macrophages
      (mono-m psi s), also induced the differentiation of cells with the distinctive
      morphological features of dendritic cells (DCs). Tumor necrosis factor (TNF) in
      combination with GM-CSF promoted further growth of both cell types but most
      notably increased the DC content. In situ analysis revealed that the cells
      exhibiting DC morphology were positive for class II major histocompatibility
      complex antigens but were CD14 negative, did not exhibit nonspecific esterase
      activity, and were nonphagocytic. Moreover, the mixed leukocyte reaction
      stimulatory capacity of cultures with the higher DC content was greater. TNF,
      interleukin-1 (IL-1), IL-6, or platelet-derived growth factor (PDGF) was inactive
      in promoting stem cell proliferation or DC morphology. IL-1 or PDGF synergized
      with GM-CSF to increase mono-m psi-associated cell proliferation but did not
      increase the DC content. The development of a common DC-monocyte precursor was
      suggested by the presence of colony-forming unit-like clusters containing mono-m
      psi s and DCs and one sharp proliferative peak. The loss of DC morphology after
      21 days, coupled with increases in mono-m psi-associated markers and a constant
      number of viable cells, further suggests that DC morphology may fluctuate in
      culture or is a transient feature acquired by certain cells of the mono-m psi
      lineage.

PMID- 1387890
TI  - Initial and delayed circulatory responses to orthostatic stress in normal humans
      and in subjects with orthostatic intolerance.
AB  - Gravitational stresses, which are common daily event for humans, result in a
      diminution in central blood volume, due to displacement of blood to the lower
      parts of the body. They demand complex adjustments in the cardiovascular system
      to offset the decrease in cardiac filling pressure. Such changes are necessary to
      sustain arterial blood pressure at an appropriate level so that there is adequate
      perfusion of vital organs, especially the brain. These adjustments must
      compensate for both the initial and sustained orthostatic stress. The rapid short
      term adaptations are mediated primarily by the cardiovascular reflexes with
      humoral agents reinforcing these reflexes during severe and prolonged orthostatic
      stress. Understanding these complex reflex adjustments in normal humans is
      necessary in order to appreciate subjects with orthostatic intolerance.

PMID- 1387892
TI  - High-frequency analysis of the signal-averaged ECG. Correlation with left
      ventricular mass in rabbits.
AB  - Standard electrocardiographic (ECG) criteria have exhibited poor correlation with
      left ventricular mass and poor sensitivity for left ventricular hypertrophy at
      acceptable levels of specificity. To assess the ability of the high-frequency
      filtered signal-averaged ECG to improve ECG correlation with left ventricular
      mass, signal-averaged orthogonal lead recordings in 29 normal rabbits and seven
      rabbits with left ventricular hypertrophy due to chronic aortic regurgitation
      were compared with left ventricular mass corrected for body weight. Voltage of
      the vector QRS complex was integrated over the total duration of the QRS after
      separate filtering with standard frequency (0-100 Hz) low-pass and high-frequency
      (44 Hz) high-pass filters. Measurement of individual X, Y, and Z lead R and S
      wave voltage was performed on averaged, standard frequency filtered complexes,
      and the maximal spatial vector magnitude was determined from the standard
      frequency filtered vectors. Voltage of the 44 Hz high-pass filtered vector QRS
      complex integrated over the total duration of the QRS (high-frequency vector
      integral) correlated closely with indexed left ventricular mass (r = 0.84, p less
      than 0.0001), significantly better than the correlation of standard frequency
      vector integral or maximal spatial vector magnitude voltages (r = 0.35 and r =
      0.61, each p less than 0.01 vs high-frequency vector integral) and the
      correlation of orthogonal lead X R wave or lead Y S wave voltages (r = 0.55 and r
      = 0.37, respectively, each p less than 0.01 vs high-frequency vector
      integral).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387893
TI  - Two cases of obsessive-compulsive disorder in individuals with Down's syndrome.

PMID- 1387894
TI  - Segmental colonic dilatation in a neonate.
AB  - Segmental dilatation of the colon is rare, usually affecting older children, and
      may mimic Hirschsprung's disease. A neonate with Down's syndrome and malrotation
      presented with this condition and was cured by segmental resection.

PMID- 1387895
TI  - Control of drug release with a combination of prodrug and polymer matrix:
      antitumor activity and release profiles of 2',3'-diacyl-5-fluoro-2'-deoxyuridine
      from poly(3-hydroxybutyrate) microspheres.
AB  - Drug release was controlled by a combination of prodrug and polymer matrix.
      Prodrugs of 5-fluoro-2'-deoxyuridine with different physicochemical properties
      were synthesized by esterification with aliphatic acids (propionate, n-butyrate,
      and n-pentanoate). Microspheres containing these ester prodrugs were prepared
      with poly(3-hydroxybutyrate) of three molecular weights (65,000, 135,000, and
      450,000). The release rates from the spheres depended on both the lipophilicity
      of the prodrug and the molecular weight of the polymer. Regardless of the
      polymer, the relative release rates were propionate greater than butyrate greater
      than pentanoate. The release of butyrate and pentanoate from the spheres
      consisting of low-molecular-weight polymer (M(r), 65,000) was faster than that
      from the spheres of higher molecular weight (M(r), 135,000 or 450,000). A single
      intraperitoneal injection of spheres of the highest molecular weight polymer
      containing butyrate or pentanoate resulted in higher antitumor effects against
      P388 leukemia in mice than did free prodrugs given over a period of five
      consecutive days. The polymer sphere itself showed low toxicity to and good
      biocompatibility with mice and rats.

PMID- 1387896
TI  - Freeze-fracture study of the site of attachment of Cryptosporidium muris in
      gastric glands.
AB  - The mode and organization of the attachment site of Cryptosporidium muris to
      gastric glands of stomach were investigated by the freeze-fracture method.
      Cryptosporidium muris was enveloped by a double membrane, of host plasma membrane
      origin, which formed the parasitophorous vacuole. The outer membrane of the
      double membrane was continuous with host plasma membrane, while the inner
      membrane was connected with the anterior part of the parasite plasma membrane at
      the annular ring. The density of intramembranous particles (IMP) was severely
      altered at the above two junctures. The parasitophorous outer membrane showed low
      IMP-density when compared to the host plasma membrane, although both membranes
      were continuous at the dense band. The inner membrane had few IMP, whereas the
      parasite plasma membrane showed numerous IMP, although both membranes were
      continuous at the annular ring. The size of dense band and annular ring was
      similar in diameter. The feeder organelle was clearly visible as membrane folds
      in freeze-fracture and some of them were connected with small vesicles of
      cytoplasm, indicating that the feeder organelle may play an important role for
      incorporation of nutrients from the host cell.

PMID- 1387897
TI  - Pulmonary hypertension and cardiac insufficiency in three cows with primary lung
      disease.
AB  - Increased pulmonary arterial pressures as a result of pulmonary disease are
      described in two cows with chronic pneumonia and one cow with acute pneumonia.
      Based on clinical signs of congestive right heart failure, increased pulmonary
      arterial pressure, and right ventricular hypertrophy, cor pulmonale was diagnosed
      in one cow. Two cows had increased pulmonary arterial pressure and signs of right
      heart insufficiency, but right ventricular hypertrophy was not identified. Two of
      the cows had ventral edema and exercise intolerance. All cows had jugular venous
      distention and increased right atrial and pulmonary arterial pressures.
      Peripheral arterial PaO2 was decreased in two cows, and not measured in the third
      cow. Although an uncommon cause of congestive heart failure in cattle at low
      altitudes, pulmonary hypertension should be considered in cattle with clinical
      right heart failure.

PMID- 1387898
TI  - Antigen presenting capacity of human decidua: no evidence for human decidual
      antigen presenting cell mediated immunoregulation.
AB  - Decidual antigen presenting cell (APC) mediated maternal immunoregulation has
      been reported. In the present study the ability of villous chorion as well as
      fetal cell pulsed early human pregnancy decidual APC to generate selectively
      antigen non-specific and MHC class II unrestricted CD8 positive T suppressor
      cells was reassessed in view of the fact that placental trophoblast, unlike the
      fetus, constitutes the fetal tissue of major contact at the maternal-fetal
      interface. Neither fetal cell nor villous chorion pulsed decidual APC generated
      maternal T cells with the ability to immunosuppress PHA-, Con A- and PWM-induced
      autologous or allogeneic lymphoproliferation. In only 2 out of 45 assays with
      villous chorion pulsed decidual APC was significant inhibition of mitogen induced
      lymphoproliferation detected and on no occasion with fetal cell pulsed decidual
      APC. No change in CD4/CD8 ratio of the maternal putative regulatory cells was
      detected by FACS analysis compared with control cultures. These findings suggest
      that decidual APC mediated immunoregulation plays no role in directing the
      maternal immune response.

PMID- 1387899
TI  - Monoclonal antibodies identify Fc gamma receptors on unfertilized human oocytes
      but not spermatozoa.
AB  - Oolemmal Fc receptors have previously been shown to play a role in the promotion
      of adhesion by antibody labeled human spermatozoa to zona-free hamster eggs. In
      this work, we demonstrated the presence of Fc gamma RI, Fc gamma RII and Fc gamma
      RIII on the oolemma of unfertilized human oocytes by means of monoclonal
      antibodies directed against these receptors, detected both by immunobead
      rosetting and indirect immunofluorescence. These receptors were also functionally
      active in that they were able to bind human aggregated IgG, human IgG-Fc, mouse
      IgG1 and IgG2a. While the presence of oolemmal IgG-Fc receptors might play a role
      in reproductive failure, by their promotion of polyspermic fertilization, in
      cases where antisperm antibodies bound to the spermatozoan surface, their role in
      the normal physiology of fertilization or in other events unrelated to sperm
      incorporation remains to be determined. In contrast, Fc gamma receptors were not
      present on human spermatozoa, irrespective of their functional state (fresh
      ejaculated, capacitated or acrosome reacted).

PMID- 1387900
TI  - Evidence for the expression of granulocyte-macrophage colony-stimulating factor
      receptors by human first trimester extravillous trophoblast and its response to
      this cytokine.
AB  - The present study has demonstrated that human extravillous trophoblast cells
      isolated from first trimester placentae can bind granulocyte-macrophage colony
      stimulating factor (GM-CSF). We have used a technique which incorporates a
      phycoerythrin (PE)-conjugated GM-CSF in association with a monoclonal antibody
      against trophoblast (BC-1) in single and double flow cytometric analysis.
      Trophoblast cells are also observed to show increased DNA synthesis in response
      to GM-CSF as assayed by [3H]thymidine incorporation and proliferative activity as
      demonstrated by double immunocytochemical staining of cells with a trophoblast
      cytokeratin marker (PKK1) and for the nuclear proliferation antigen (Ki-67).
      These findings provide evidence that human extravillous trophoblast expresses
      receptors for GM-CSF and responds to this cytokine.

PMID- 1387901
TI  - Enrichment of gamma delta T lymphocytes in human semen: relation between gamma
      delta T cell concentration and antisperm antibody status.
AB  - The presence and relative concentrations of T lymphocytes bearing the alpha beta
      and gamma delta cell receptor (TCR) in human semen were assessed and related to
      the occurrence of auto-antibodies to sperm in semen and peripheral blood. Using
      an immunoperoxidase technique, and monoclonal antibodies to the beta chain and
      delta chain of the human TCR, both alpha beta and gamma delta T cells were
      detected in each of 30 semen samples examined. In seven men with antisperm
      antibodies both on their ejaculated sperm and in their serum, the mean
      concentrations of gamma delta and alpha beta T cells were 3,560 and 3,230
      cells/ml semen, respectively. In seven men with antisperm antibodies in serum
      only, the concentrations of gamma delta and alpha beta T cells were 860 and 1,280
      cells/ml, while in 16 men with no evidence of auto-immunity to sperm there was a
      mean of 350 gamma delta T cells and 610 alpha beta T cells/ml. In contrast, the
      concentrations of gamma delta and alpha beta T cells in peripheral blood from
      these same men were unrelated to antisperm antibody status. The mean ratio of
      alpha beta to gamma delta T cells in peripheral blood of all subjects was 12. The
      ratio of alpha beta to gamma delta T cells in semen were 0.9 for men with sperm
      bound and serum antisperm antibodies, 1.5 for men with antisperm antibodies in
      serum only and 1.7 for men lacking these auto-antibodies. These results were
      confirmed by FACS analysis. Thus, gamma delta T cells in human semen comprise a
      greatly increased proportion of the total T cell population as compared to the
      circulation. In addition, the relative and absolute concentration of gamma delta
      T cells are further elevated in semen from men with evidence of localized auto
      immunity to their own sperm. These results suggest that gamma delta T cells may
      function in immune surveillance in the non-sterile proximal portions of the male
      genital tract and that replication of T cells bearing the gamma delta TCR
      accompanies an autoimmune response to sperm.

PMID- 1387902
TI  - Proceedings of the 20th annual meeting of the American Association of Gynecologic
      Laparoscopists. Las Vegas, Nevada, November 13-17, 1991.

PMID- 1387903
TI  - The wonder of not knowing.

PMID- 1387904
TI  - Endoscopic treatment of endometriosis-associated infertility. Therapeutic,
      economic and social benefits.
AB  - In this report on the therapeutic results in patients with moderate and severe
      endometriosis treated by operative laser laparoscopy, we also present a
      comparative analysis of cost and duration of hospitalization and of convalescence
      in comparable patients treated by laparoscopy versus laparotomy. Sixty patients
      treated by the same surgeon with operative laser laparoscopy were followed for a
      period of at least one year to calculate cumulative pregnancy rates, monthly
      fecundity rates, and monthly probability of pregnancy. The mean duration of
      hospitalization and incapacitation as well as physician and hospital costs
      incurred by the laparoscopy treated patients were compared with those incurred by
      60 patients with similar degrees of endometriosis but treated by microsurgery at
      laparotomy. In the laparoscopy group, 36 patients had stage III and 24, stage IV
      endometriosis. Monthly fecundity rates (6.7%), monthly probability of pregnancy
      (12.6%) and cumulative pregnancy rates (70.5%) did not differ between patients
      with stage III and IV disease. The total number of hospital days required by the
      60 laparoscopy patients was 72 versus 258 for the laparotomy patients (P less
      than .001). The total number of days' incapacitation for laparoscopy patients was
      216 versus 1,284 for the laparotomy group (P less than .001). The total cost of
      medical care was $223,260 for the laparoscopy group and $424,500 for the
      laparotomy group (P less than .001). Our results validate the therapeutic
      efficacy of operative laparoscopy in the treatment of moderate and severe
      endometriosis and confirm the substantial economic and social benefits of
      laparoscopy surgery over laparotomy.

PMID- 1387907
TI  - Management of ovarian masses. AAGL 1990 survey.
AB  - The American Association of Gynecologic Laparoscopists (AAGL) membership was
      surveyed on the use of laparoscopy in the management of persistent ovarian masses
      in 1990. A total of 13,739 laparoscopies were performed for this indication.
      Ninety-six percent of the respondents performed laparoscopy for this indication
      on premenopausal women only. Among respondents performing laparoscopy for
      suspected cancer, there was a 14% conversion rate to laparotomy, compared to 9%
      among those who performed direct laparotomies when cancer was suspected. An
      overall incidence of 4 per 1,000 cases of stage I ovarian cancer was found, and
      about 70% of women with persistent adnexal masses were managed by laparoscopy
      alone. The risks to women with cancer, as well as the benefits to those without,
      are discussed.

PMID- 1387906
TI  - Laparoscopic appendectomy using a single umbilical puncture (minilaparoscopy).
AB  - The surgical outcome of the first 25 patients in whom the Pelosi single-puncture
      laparoscopic appendectomy technique was employed demonstrates the new approach as
      a safe, inexpensive and effective alternative to the currently used multiple
      puncture method. The results suggest single-puncture (minilaparoscopy) operative
      endoscopy as the ultimate goal in the progression of minimally invasive surgery.

PMID- 1387905
TI  - Laparoscopic aspiration of ovarian endometriomas. Effect with postoperative
      gonadotropin releasing hormone agonist treatment.
AB  - In the period 1988-1990 this prospective study of 33 women with moderate or
      severe endometriosis who underwent laparoscopy for infertility and/or chronic
      pelvic pain, was conducted to evaluate the efficacy of aspirating endometriotic
      cysts followed by administration of a gonadotropin releasing hormone (GnRH)
      agonist in reducing the size of ovarian endometriomas. The cysts (mean diameter,
      4.5 cm; range, 2-7; unilateral, 21 cases; bilateral, 12 cases) were punctured,
      aspirated, washed and emptied completely. After laparoscopy, 15 subjects received
      goserelin administered as a 28-day subcutaneous depot for three months, whereas
      18 patients undergoing simple observation constituted internal controls.
      Ultrasound scans were performed before and at one, three and six months after
      laparoscopy. One case and three controls requested surgery between the four- and
      five-month follow-up scans and did not complete the study. All the other women
      had recurrent cysts at the six-month scan. There were no significant differences
      in mean endometrioma diameter between the two groups at any observation time nor
      between prelaparoscopic and six-month ultrasound examinations within each
      treatment group. We conclude that aspiration and washing of endometriotic cysts,
      combined with postoperative administration of GnRH agonists or not, is
      ineffective.

PMID- 1387908
TI  - Management of adnexal masses by operative laparoscopy. Selection criteria.
AB  - The management of adnexal masses by operative laparoscopy is controversial. The
      application of strict criteria for preoperative patient selection and careful
      intraoperative assessment and management are critical to the appropriate use of
      this approach. Clinical examination, ultrasound imaging of the pelvis and the
      addition of the CA-125 tumor marker in postmenopausal women can aid in the
      selection of a population at low risk for malignancy that may be appropriate for
      operative laparoscopic adnexal surgery. Recommended procedures include careful
      intraoperative inspection of the pelvis and abdomen, liberal use of frozen
      sections, and conversion to immediate-staging laparotomy when malignancy is
      found.

PMID- 1387909
TI  - Laparoscopic uterine suspension.
AB  - Laparoscopic uterine suspension is an effective method of correcting symptomatic
      uterine retroversion. Eighty patients with deep dyspareunia reproduced by
      palpation of their retroverted uterus underwent a modified Gilliam uterine
      suspension under laparoscopic visualization. There were no intraoperative or
      postoperative complications requiring laparotomy, and symptoms were relieved in
      74 patients.

PMID- 1387910
TI  - Incidence of bowel injury due to dense adhesions at the sight of direct trocar
      insertion.
AB  - A retrospective review of 4,532 outpatient laparoscopic procedures was conducted
      to determine the frequency of dense bowel adhesions at the level of the
      umbilicus. The umbilicus is the classical site of entry for the laparoscopic
      trocar. Using direct trocar insertion in all cases we encountered four bowel
      injuries. Bowel adhesion to the insertion site was noted in one case.

PMID- 1387911
TI  - Jordan M. Phillips, M.D.--postdoctoral educator at large.
AB  - Twenty years ago Jordan Phillips recognized the importance of laparoscopy and
      aroused the interest of gynecologists by founding the American Association of
      Gynecologic Laparoscopists (AAGL). Within five years he had expanded the teaching
      mission of the AAGL to microsurgery, which revolutionized infertility surgery.
      Through his insatiable personal drive, he catalyzed the movement of people and
      ideas on an international level by organizing numerous postgraduate courses in
      North America, Europe and Asia, and later Australia and South America. Through
      his untiring efforts as an educator, Jordan Phillips has played a major role in
      preparing gynecologists in many parts of the world for the commanding position of
      advanced laparoscopic surgery, hysteroscopy and microsurgery in gynecologic
      practice.

PMID- 1387912
TI  - Nd:YAG laser laparoscopic coagulation of symptomatic myomas.
AB  - The Nd:YAG laser dispersion effect, 2-5 mm in diameter, is utilized in a new
      laparoscopic procedure to coagulate and reduce symptomatic serosal and intramural
      myomas of moderate size (less than or equal to 10 cm). Depot leuprolide
      pretreatment for 2-6 months resulted in 40-60% shrinkage. Seventy-five patients
      35-50 years old with symptomatic myomas, pain and pressure then underwent Nd:YAG
      laser coagulation for thorough devascularization of uterine myomas. Postoperative
      transvaginal ultrasound one, three and six months later showed the myomas reduced
      an average of 50-70% beyond the effect attributable to leuprolide. In two groups
      of patients whose myomas measured 5-10 cm and 3-5 cm after leuprolide
      pretreatment, laser coagulation subsequently reduced the myomas an average of
      50%. In patients with postleuprolide myomas of 2-3 cm, virtually no myomas were
      identified postoperatively. The patients were followed up to 14 months. This
      laparoscopic procedure can be used in patients approaching menopause who wish to
      avoid abdominal myomectomy or hysterectomy.

PMID- 1387913
TI  - Laparoscopic management of ovarian dermoid cysts.
AB  - Benign cystic teratoma (dermoid cyst) was managed laparoscopically in 25 cases
      (16 cyst excisions and 9 oophorectomies). Surgical procedures to avoid spill
      during ovarian cystectomy and oophorectomy were developed (14 cases). This series
      demonstrates a gradual evolution in surgical technique. Surgical outcome was good
      in all cases, complications were rare, and the procedure required a hospital stay
      less than 24 hours.

PMID- 1387914
TI  - Direct binding of small nuclear ribonucleoprotein G to the Sm site of small
      nuclear RNA. Ultraviolet light cross-linking of protein G to the AAU stretch
      within the Sm site (AAUUUGUGG) of U1 small nuclear ribonucleoprotein
      reconstituted in vitro.
AB  - The major small nuclear ribonucleoproteins (snRNPs) U1, U2, U5 and U4/U6
      participate in the splicing of pre-mRNA. U1, U2, U4 and U5 RNAs share a highly
      conserved sequence motif PuA(U)nGPu, termed the Sm site, which is normally
      flanked by two hairpin loops. The Sm site provides the major binding site for the
      group of common proteins, B', B, D1, D2, D3, E, F and G, which are shared by the
      spliceosomal snRNPs. We have investigated the ability of common snRNP proteins to
      recognize the Sm site of snRNA by using ultraviolet light-induced RNA-protein
      cross-linking within U1 snRNP particles. The U1 snRNP particles, reconstituted in
      vitro, contained U1 snRNA labelled with 32P. Cross-linking of protein to this U1
      snRNA occurred only in the presence of the single-stranded stretch of snRNA that
      makes up the conserved Sm site. Characterization of the cross-linked protein by
      one and two-dimensional gel electrophoresis indicated that snRNP protein G had
      become cross-linked to the U1 snRNA. This was confirmed by specific
      immunoprecipitation of the cross-linked RNA-protein complex with an anti-G
      antiserum. The cross-link was located on the U1 snRNA by fingerprint analysis
      with RNases T1 and A; this demonstrated that the protein G has been cross-linked
      to the AAU stretch within the 5'-terminal half of the Sm site (AAUUUGUGG). These
      results suggest that the snRNP protein G may be involved in the direct
      recognition of the Sm site.

PMID- 1387916
TI  - Treatment of radiation-induced renal artery stenosis: reconstructive surgery or
      angioplasty?

PMID- 1387915
TI  - Refined 1.8 A crystal structure of the lambda repressor-operator complex.
AB  - The crystal structure of the lambda repressor-operator complex has been refined
      to an R-factor of 18.9% at 1.8 A resolution. This refinement, using data
      collected at low temperature, has revealed the structure of the N-terminal arm
      and shows that the interactions of repressor with the two halves of the pseudo
      symmetric operator site are significantly different. The two halves of the
      complex are most similar near the outer edge of the operator site (in a region
      where the lambda and 434 repressors make similar contacts), but they become
      increasingly different toward the center of the operator. There are striking
      differences near the center of the site where it appears that the arm makes
      significant contacts to only one half of the DNA site. This suggested a new way
      of aligning the operator sites in phage lambda. The high resolution structure
      confirms many of the previously noted features of the complex, but also reveals a
      number of new protein-DNA contacts. It also gives a better view of the extensive
      H-bonding networks that couple contacts made by different residues and different
      regions of the protein, and reveals important new details about the helix-turn
      helix (HTH) region, and the positions of many water molecules in the complex.

PMID- 1387917
TI  - Effects of atrial natriuretic peptide on glycerol induced acute renal failure in
      the rat.
AB  - Acute and chronic experiments were performed in rats to examine whether atrial
      natriuretic peptide (ANP) has any beneficial effects on glycerol-induced acute
      renal failure (ARF). ANP infusion (Atriopeptin III, 1.0 microgram/kg+0.2
      microgram/kg/min) improved the renal blood flow (RBF) and the glomerular
      filtration rate (GFR), and induced profound natriuresis in the early stage of
      ARF. By contrast, ANP decreased RBF in the control rats. In addition to these
      acute hemodynamic effects, long-term beneficial effects of ANP were also
      observed. A 75-min infusion of ANP significantly lessened the degree of azotemia
      as well as the extent of renal histologic damage assessed 24 hours after the
      glycerol injection. These results indicate that ANP can afford partial protection
      against both acute renal dysfunction and the chronic course of the glycerol
      induced ARF, suggesting that ANP may be useful in the treatment of ARF.

PMID- 1387918
TI  - Blood velocity patterns in poststenotic regions and velocity waveforms for
      myocardial inflow associated with coronary artery stenosis in dogs.
AB  - Velocity profiles across a vessel were investigated in poststenotic regions of
      the canine left coronary artery by our 80-channel 20 MHz ultrasound velocimeter.
      The velocity waveform in a small artery just before its penetration into
      myocardium was measured by our laser Doppler method. The poststenotic velocity
      configuration was characterized by a narrow region of high velocity with
      diastolic reverse flow near the wall which may dissipate energy. The velocity
      waveform in the distal small arteries exhibited increased systolic reverse flow
      with decreased diastolic forward flow, resulting in a remarkable reduction of
      coronary inflow into the myocardium.

PMID- 1387920
TI  - Effects of morphine on the phenotypic expression of cell surface markers on
      murine lymphocytes.
AB  - There is a growing literature indicating that opioid abuse by human addicts and
      opioid administration to animals have profound effects on the immune system. In
      the present study, implantation of morphine pellets in mice was associated with
      reduced phenotypic expression of the cell surface antigens specific to T
      lymphocytes and to helper and cytotoxic/suppressor T-lymphocyte subtypes. The
      effect of morphine, as measured by flow cytometry using monoclonal antibodies
      specific for antigens expressed by these cells, was dose-dependent. The decrease
      in expression of antigens was apparent as early as 24 h after morphine pellet
      implantation and continued for 3 days. In addition, a time-dependent increase in
      the expression of these antigens was observed in placebo- and morphine-treated
      mice, suggesting that the pellets had a small antigenic effect. However, at all
      times studied, morphine-treated mice had fewer cells expressing the antigens than
      placebo-treated mice. Our results provide additional evidence that the use of
      opioids by IV drug abusers compromises their immune function.

PMID- 1387919
TI  - Insights from in-vitro flow visualization into the mechanism of systolic anterior
      motion of the mitral valve in hypertrophic cardiomyopathy under steady flow
      conditions.
AB  - Hypertrophic obstructive cardiomyopathy is a heart disease characterized by a
      thickened interventricular septum which narrows the left ventricular outflow
      tract, and by systolic anterior motion (SAM) of the mitral valve which can
      contact the septum and create dynamic subaortic obstruction. The most common
      explanation for SAM has been the Venturi mechanism which postulates that septal
      hypertrophy, by narrowing the outflow tract, produces high velocities and thus
      low pressure between the mitral valve and the septum, causing the valve leaflets
      to move anteriorly. This hypothesis, however, fails to explain why SAM often
      begins early in systole, when outflow tract velocities are low or negligible or
      why it may occur in the absence of septal hypertrophy. The goal of this study was
      therefore to investigate an alternative hypothesis in which structural
      abnormalities of the papillary muscles act as a primary cause of SAM by altering
      valve restraint and thereby changing the geometry of the closed mitral apparatus
      and its relationship to the surrounding flow field. In order to test this
      hypothesis, an in vitro model of the left ventricle which included an explanted
      human mitral valve with intact chords and papillary muscle apparatus was
      constructed. Flow visualization was used to observe the ventricular flow field
      and the mitral valve geometry. Displacing the papillary muscles anteriorly and
      closer to each other, as observed clinically in patients with cardiomyopathy and
      obstruction produced SAM in the absence of septal hypertrophy. Flow could be seen
      impacting on the upstream (posterior) surface of the leaflets; such flow is
      capable of producing form drag forces which can initiate and maintain
      SAM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387921
TI  - Sequence comparison of the capsid region of hepatitis E viruses isolated from
      Myanmar and China.
AB  - Hepatitis E viruses (HEVs) were isolated during epidemics, one from Myanmar
      (formerly called Burma) and one from China and were partially sequenced. Another
      HEV Myanmar strain from sporadic hepatitis was previously sequenced by us. A cDNA
      sequence comparison was performed among them in the 3'-terminal region,
      approximately 750-base long. This region contained at least two immunological
      epitopes and was considered to correspond to the structural protein. The
      nucleotide sequence identity was 97.2% between the two Myanmar strains and 93.3
      and 92.5% between the two Myanmar and the China strain. The deduced amino acid
      sequence identity ranged from 98.4 to 100.0% among the three strains. Thus this
      segment was well conserved on the amino acid level among the different strains
      isolated from these two Asian countries, although the China strain diverged more
      from the Myanmar strains on the nucleotide sequence level. This data may provide
      important information for the development of a vaccine and for identification of
      the virological link between different geographical locations.

PMID- 1387922
TI  - Infection control.

PMID- 1387923
TI  - Reduction of thyroid hormone receptor c-ERB A alpha mRNA levels in the
      hippocampus of Alzheimer as compared to Huntington brain.
AB  - A history of thyroid dysfunction has been cited as a possible risk factor for
      Alzheimer's disease (AD). Neurologic symptoms displayed by hypothyroid patients
      resemble, in part, those manifested by Alzheimer patients. To determine if a
      relationship exists between thyroid hormone receptor message levels and AD, in
      situ hybridization with tritiated antisense RNA probes for thyroid hormone
      receptors was used to examine the expression of these genes in Alzheimer and
      Huntington brain tissue. Message levels for a thyroid hormone receptor highly
      expressed in brain (c-ERB A alpha) was reduced by 52% in CA1 and 43% in CA2 in
      Alzheimer hippocampus as compared to Huntington controls. In contrast, message
      levels for another form of thyroid hormone receptor (c-ERB A beta 1) in Alzheimer
      hippocampus were not significantly different from Huntington controls. Temporal
      and cerebellar levels of c-ERB A alpha were elevated by 1.6-fold whereas temporal
      but not cerebellar levels of c-ERB A beta 1 were elevated 2.0-fold in Alzheimer
      brain. There was no correlation between thyroid hormone receptor levels and brain
      weight, autopsy interval, patient age, or the extent of neurofibrillary
      degeneration. Instead, decreased thyroid hormone receptor mRNA levels in
      Alzheimer-affected hippocampus were due to an increase in the percentage of
      neurons expressing lower message levels for these proteins.

PMID- 1387925
TI  - Reasonable accommodation.

PMID- 1387924
TI  - Presynaptic serotonin mechanisms in rats subjected to inescapable shock.
AB  - After exposure to uncontrollable shock training, two distinct groups of rats can
      be defined in terms of their performance in learning to escape from a
      controllable stress. Learned helpless rats do not learn to terminate the
      controllable stress, whereas non-learned helpless rats learn this response as
      readily as naive control rats do. The present studies were designed to examine
      the correlations between the behavioral differences and the changes of
      presynaptic serotonergic activity, seen in these groups of rats. The major
      findings concerned presynaptic serotonergic effects in the hippocampus and
      hypothalamus of learned helpless rats. In the hippocampus, these included a
      statistically significant increase in three presynaptic 5-hydroxytryptamine (5
      HT) mechanisms: K(+)-induced release of [3H]serotonin, high affinity uptake of
      [3H]serotonin and maximum density of binding sites for uptake of 5-HT, measured
      with [3H]paroxetine. In the hypothalamus, there was a differential modulation of
      all three presynaptic 5-HT mechanisms. A significant decrease in: K(+)-induced
      release of [3H]serotonin, in high affinity uptake of [3H]serotonin and the
      maximum binding site density of [3H]paroxetine binding was observed. No changes
      in uptake site binding was seen in other regions of the brain examined. These
      results implicate presynaptic serotonin mechanisms in the behavioral deficit
      caused by uncontrollable shock. In addition, a limbic-hypothalamic pathway may
      serve as a control center for the behavioral response to stress.

PMID- 1387926
TI  - Mechanism of the anti-emetic activity of 5-HT3 receptor antagonists.
AB  - Ondansetron, a potent and highly selective 5-HT3 receptor antagonist, prevents
      emesis following chemotherapy by antagonising the action of 5-hydroxytryptamine
      (5-HT) at 5-HT3 receptors on vagal afferent neurons that innervate the
      gastrointestinal tract and 5-HT3 receptors in the central vomiting system.
      Evidence suggests that chemotherapy induces the release of 5-HT from
      enterochromaffin cells in the small intestine. This stimulates vagal afferent
      nerves via 5-HT3 receptors. Information is then relayed, via the vagus nerve, to
      the central vomiting system. 5-HT3 receptors are also found in the hind-brain
      vomiting system including the area postrema (the site of the chemoreceptor
      trigger zone for emesis). Therefore, following chemotherapy, 5-HT activates 5-HT3
      receptors at 2 sites to induce emesis. Clinical data showing that a single dose
      of ondansetron prevents acute emesis suggest that it is important to block the
      initiation of the emetic reflex. This may prevent the recruitment of central
      mechanisms involving 5-HT3 receptors.

PMID- 1387927
TI  - The effectiveness of a single intravenous dose of ondansetron.
AB  - This paper reviews data from 3 randomised, double-blind, parallel-group studies
      carried out in patients receiving high-dose cisplatin chemotherapy (50-120
      mg/m2). These comparative trials show that a single intravenous dose of
      ondansetron (8-32 mg) is as effective as the continuous infusion and intermittent
      dose regimens used in previous clinical trials (8 mg i.v. followed by a 1 mg/h
      infusion for 24 h and 0.15 mg/kg i.v. x 3). One of the studies, carried out in
      Europe, demonstrated that a single 8 mg i.v. dose was as effective as 32 mg given
      either as an 8 mg loading dose followed by an infusion or as a single intravenous
      dose of 32 mg before chemotherapy. A similar study conducted in the United States
      showed that a 32 mg i.v. single dose was significantly more effective than both
      the 8 mg i.v. dose and the intermittent dose schedule. This study used a
      prospective stratification based on the dose of cisplatin (50-70 mg/m2 and
      greater than or equal to 100 mg/m2). In both strata the 32 mg dose was superior.
      These results emphasise the importance of selecting the dose of ondansetron (8-32
      mg) based on factors that predispose patients to emesis, e.g., female gender,
      patients with a history of chemotherapy or motion sickness and the dose of
      cisplatin. The ondansetron dosing regimen for patients receiving a highly
      emetogenic chemotherapy (8-32 mg i.v. followed by 8 mg orally twice daily) is
      both simple and flexible.

PMID- 1387928
TI  - Ondansetron as prophylaxis for chemotherapy and radiotherapy-induced emesis in
      children.
AB  - Ondansetron was given as anti-emetic prophylaxis to 429 children receiving a
      variety of emetogenic cancer treatments for up to 8 days, in three, open,
      multicentre, European studies. Children aged between 6 months and 17 years with a
      variety of tumours and receiving chemotherapy or chemotherapy plus total body
      irradiation (TBI) were studied. Ondansetron was given intravenously, 5 mg/m2 or 8
      mg, according to the surface area of the child, immediately before chemotherapy.
      Intravenous or oral treatment (2, 4 or 8 mg, according to surface area) was
      continued 3 times a day during chemotherapy or TBI, and for a further 2 days (non
      cisplatin chemotherapy or TBI) or 5 days (cisplatin chemotherapy). The number of
      vomits and retches (each counting as an emetic episode) were recorded daily, as
      was an assessment of nausea, which was graded as none (not feeling sick at all),
      mild (feeling sick) or severe (feeling very sick). Responses were graded
      according to the number of emetic episodes during the worst 24-hour period. In
      addition, response was expressed in terms of emesis-free days as a proportion of
      all ondansetron treatment days. During chemotherapy, 66% of children experienced
      less than 3 emetic episodes on their 'worst day' and 88% had none or mild nausea.
      Sixty-eight percent of all ondansetron treatment days (2,131) were free of
      emesis. Of the patients who were poorly controlled with 'customary' anti-emetics,
      at least 81% experienced better control with ondansetron. When analysed according
      to the most emetogenic agent given 36, 59 and 75% of children reported less than
      3 emetic episodes on their 'worst day' respectively, during cisplatin, ifosfamide
      and other less emetogenic chemotherapy. During conditioning for bone marrow
      transplantation with cyclophosphamide and TBI, 80 and 57% of patients,
      respectively, experienced less than 3 emetic episodes. The overall incidence of
      adverse events was low and headache (reported in 4% of patients) was the only
      event reported by more than 1% of patients. These studies show that ondansetron
      is a safe, well tolerated and an effective anti-emetic in the treatment of
      children receiving a wide variety of chemotherapy regimens.

PMID- 1387929
TI  - Ondansetron compared with metoclopramide in the control of emesis and quality of
      life during repeated chemotherapy for breast cancer.
AB  - This was a multicentre, randomised, double-blind, parallel-group study which
      included female breast cancer patients, receiving their first of 6 scheduled
      courses of chemotherapy (cyclophosphamide greater than or equal to 500 mg/m2).
      Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg
      ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing
      with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total
      of 93 patients were treated with ondansetron and 94 patients with metoclopramide.
      On day 1 of their first course of treatment 91 and 60% of patients in the
      ondansetron and metoclopramide groups respectively were free of emesis (p less
      than 0.001). Over the 5-day treatment period, the corresponding figures were 81
      and 48% (p less than 0.001). The results for nausea also revealed highly
      statistically significant treatment differences (p less than 0.001) in favour of
      ondansetron for both day 1 and day 1-5 analyses of the first treatment course.
      Over the series of courses, 67% of patients receiving ondansetron completed all 6
      courses with a maximum of 2 emetic episodes on their worst day, compared with 28%
      of patients receiving metoclopramide (p less than 0.001). A similar analysis for
      nausea revealed that 49% of patients receiving ondansetron completed all 6
      courses with 'none' or 'mild' nausea compared with 27% of patients receiving
      metoclopramide (p less than 0.001). These differences were reflected in quality
      of life data (Rotterdam Symptom Checklist). After the first course of treatment,
      a statistically significant improvement (p = 0.002) in the psychological subscale
      scores was observed after ondansetron compared with metoclopramide. No
      differences were observed in the physical or functional activity subscales after
      the first course. However, the quality of life results over the series of courses
      revealed a more pronounced difference in favour of ondansetron in the
      psychological subscale scores (p less than 0.001) as well as trends in favour of
      ondansetron in the physical (p = 0.096) and functional activity (p = 0.056)
      subscales. Extrapyramidal symptoms were reported in 19% of patients in the
      metoclopramide group and resulted in 15% of patients withdrawing from their
      randomised anti-emetic schedule, either during or between treatment courses.
      Other adverse events were generally minor in nature and did not necessitate
      withdrawal from treatment. In conclusion, this study shows that ondansetron is
      significantly superior to metoclopramide (each with a single pre-treatment dose
      of dexamethasone) in the control of emesis over 6 courses of chemotherapy for
      breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1387930
TI  - A comparison of ondansetron with alizapride plus methylprednisolone in the
      control of cisplatin-induced emesis. The French Pneumology Group for the
      Ondansetron Study.
AB  - This randomised, single-blind, parallel-group study was carried out in 48 French
      pneumology centres to compare the anti-emetic efficacy of ondansetron and an
      alizapride plus methylprednisolone (ALI/MPS) combination in patients receiving
      high-dose cisplatin. A total of 220 patients were recruited of whom 209 were
      evaluable (100 on ondansetron and 109 on ALI/MPS). Thirty minutes before
      cisplatin, patients received either ondansetron (8 mg i.v.) or alizapride (4
      mg/kg i.v.) combined with methylprednisolone (500 mg i.v.). The ondansetron and
      alizapride injections were repeated 4 and 8 h later. Thereafter, patients
      received oral ondansetron (8 mg) or alizapride (50 mg) 3 times daily for 5 days.
      Ondansetron was significantly superior to ALI/MPS in the control of acute emesis
      (p less than 0.001); 88/100 (88%) of ondansetron, and 69/109 (63%) of ALI/MPS
      patients experienced less than 3 emetic episodes. Similarly, ondansetron was
      superior to ALI/MPS for the control of acute nausea (visual analogue scale at 24
      h; 13 vs. 22 mm respectively, p = 0.0012). The superiority of ondansetron over
      days 2-6 was not as great as that over the first 24 h, although there was a trend
      in favour of ondansetron. More patients treated with ondansetron wished to take
      the same anti-emetic treatment again (83% for ondansetron vs. 56% for ALI/MPS, p
      less than 0.001). Both treatments were well tolerated. This study shows that
      ondansetron is superior to a benzamide-corticosteroid combination in the control
      of acute cisplatin-induced emesis.

PMID- 1387931
TI  - [Fixed drug-induced exanthema caused by novorin nose drops].
AB  - The case of a 36-year-old woman with typically fixed drug eruption is reported. A
      detailed case history and the diary of the patient helped to reveal the drug
      (Novorin nose drops) which caused the disease. It was proved by the lymphocyte
      transformation test.

PMID- 1387932
TI  - The role of subendothelial laminin and platelet laminin receptors in haemostasis.
AB  - Laminin (LM) is a basement membrane glyco-protein which exhibits a number of
      biological activities, including the promotion of cell attachment and migration.
      In a static system, platelets attach to LM without spreading. In order to
      elucidate the mechanisms mediating platelet-LM interactions under flow
      conditions, we studied the effects of blocking subendothelial LM and its platelet
      receptor. We measured the extent of platelet adhesion to the endothelial cell
      extracellular matrix (ECM) using a parallel plate perfusion chamber. To do this,
      we performed the following experiments: i) blockade of subendothelial LM by
      incubation of ECM with an anti-LM antibody (Ab); ii) blockade of the platelet
      receptor for LM with: a) an anti-67 KDa receptor Ab; and b) three different LM
      derived peptides (CFALRGDNP, IKVAV and CDPGYIGSR). In i) perfusates consisted of
      whole blood, whereas in ii) perfusates were prepared with washed platelets pre
      incubated with Ab or peptides and reconstituted with plasma and washed red blood
      cells. Perfusions were carried out at 800 s-1 shear rate. Platelet deposition was
      morphometrically evaluated by a computerized system. Our results indicated that
      when ECM was pre-incubated with an anti-LM Ab (100 micrograms/ml, 30 min, 37
      degrees C) a reduction of the surface coverage (SC) of 23.3 +/- 2.3% (p less than
      0.01) was observed. When washed platelets were pre-incubated with an anti-67 KDa
      receptor Ab (40 micrograms/ml, 30 min, 37 degrees C) their interaction with ECM
      was decreased by 22.3 +/- 2.1% of SC (p less than 0.005). In other experiments
      platelets were pre-incubated with CFALRGDNP, IKVAV and CDPGYIGSR (200
      micrograms/ml, 30 min, 37 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387933
TI  - Effects of adrenaline infusion on serum thromboxane B2 and plasma beta
      thromboglobulin levels in hypertensive and normotensive subjects.
AB  - Adrenaline was infused in incremental doses of 0.05 up to 0.1 microgram/kg/min
      over a 60-min period in nine patients with mild essential hypertension and six
      age-matched normotensive controls. Blood samples were drawn at preset time
      intervals and plasma adrenaline, platelet count, serum thromboxane B2 (TxB2) and
      plasma beta-thromboglobulin (beta-TG) were measured. Adrenaline levels (m +/-
      SEM) rose significantly, from 0.078 +/- 0.01 (baseline) to 0.902 +/- 0.03 ng/ml
      (60 min), in the hypertensive group; a similar increase was observed in the
      control group (from 0.049 +/- 0.007 to 0.877 +/- 0.03 ng/ml). Platelet count
      increased significantly at early time points and remained high throughout
      infusion in both groups (hypertensive from 250 +/- 25 to 305 +/- 24 x
      10(3)/microliters, control from 219 +/- 16 to 260 +/- 18 x 10(3)/microliters).
      TxB2 levels likewise increased significantly from 15 minutes after initiation of
      infusion. In hypertensive subjects the mean resting value of 186 +/- 17 ng/ml
      rose to 312 +/- 42 ng/ml, while in control subjects the resting value of 174 +/-
      29 ng/ml rose to 286 +/- 32 ng/ml. Baseline levels of TxB2 were found to be
      higher in the hypertensive patients but not significantly. beta-TG levels
      increased from an initial value of 43.84 +/- 3.69 ng/ml to 59.5 +/- 4.69 ng/ml at
      60 min in the hypertensive group, while a similar change from 28.7 +/- 19.2 ng/ml
      to 40.36 +/- 3.16 ng/ml was observed in the control group. These changes were
      significant, as was the difference between basal values in the two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1387934
TI  - [Electrocardiographic changes in patients with airway obstruction].
AB  - In severe bronchial asthma reversible electrocardiographic abnormalities are not
      rare. It is usually sinus tachycardia, right axis deviation, atrial enlargement
      and right bundle branch block. Transient ST-segment depression or elevation in
      inferior leads in severe acute asthma has been observed since long. Adrenergic
      stimulation, hyperventilation, hyperinflation and primary or secondary coronary
      insufficiency were as a causes. Severity of ECG signs correlated with the degree
      of airway obstruction. Our study was aimed at investigation of
      electrocardiographic abnormalities in chronic pulmonary obstructive disease and
      asthma and to assess the relationship of the extent of airway obstruction to the
      frequency of ECG changes. Correlation was found of ECG manifestation of sinus
      tachycardia, right ventricle hypertrophy. ventricular premature complex, right
      bundle branch block with the degree of airway obstruction.

PMID- 1387936
TI  - [Antibiotic assay. Indications and application].

PMID- 1387935
TI  - 5-Hydroxytryptamine1A receptor agonists in animal models of depression and
      anxiety.
AB  - The effects of different doses of buspirone, 3-dipropyl-amino-5-hydrochromar (NDO
      008) and 8-hydroxydipropyl-aminotetralin (8-OH-DPAT) (administered
      intraperitoneally) were studied in tests of anxiolytic and antidepressant action
      in rats. These tests included the elavated plus maze test, the forced swim test,
      stress-induced suppression of open-field behavior, and the differential
      reinforcement-of-low-rates-of-behaviour-72 sec (DRL 72 s) test. Buspirone (0.125
      mg/kg) and NDO 008 (1.0 to 2.0 mg/kg) produced anxiolytic activity in the
      elevated plus maze, whereas 8-OH-DPAT did not in the doses employed. All three
      compounds increased activity in the forced swim test, although buspirone did so
      at a lower dose than NDO 008 and 8-OH-DPAT. In the stress-induced suppression
      test of open field activity all three compounds induced an antidepressant-like
      effect at different doses dependent on whether footshock (stressor) was presented
      24 hr before or just prior to the open-field test. All three compounds even
      caused some reduction of activity in the non-shocked rats. 8-OH-DPAT (1.0 mg/kg)
      produced a significant and reliable increase in the Reinforcement/Response rate
      quotient in the DRL 72s test. These diverse results may provide an indication of
      potential clinical efficacy of the 5-HT1A agonists in the treatment of anxiety
      and depression.

PMID- 1387937
TI  - [Primary amenorrhea revealing micropolycystic ovary syndrome].
AB  - Nine patients with polycystic ovary syndrome revealed by primary amenorrhea were
      studied clinically, biochemically and ultrasonographically. One of them had
      excess weight, four had hirsutism and five acne. Testosterone and delta 4
      androstenedione levels were high in all patients. Luteinizing hormone (LH) basal
      levels were increased in five patients. Basal values of follicle-stimulating
      hormone (FSH) remained within normal range. The LH to FSH ratio was elevated
      (over 2) in six patients. The LSH response to gonadotropin-releasing hormone
      (GnRH) was explosive in all patients. Ultrasonography showed that three out of
      five patients had enlarged ovaries with multiple follicles not exceeding 8 mm.
      Following treatment, two patients had children after ovulation was induced with
      clomiphene citrate, one patient became pregnant spontaneously but thereafter
      opted for voluntary interruption; two patients are still on ovulation-inducing
      therapy; four patients still have contraception. These results indicate the
      clinical heterogeneity and the diagnostic problems that surround this uncommon
      form of a frequently observed disease.

PMID- 1387938
TI  - [Digital necrosis in Raynaud's phenomenon revealing a testicular seminoma. Value
      of prostacyclin].
AB  - A testicular tumour could be diagnosed by the occurrence of a Raynaud's
      phenomenon complicated by severe digital arteritis. The arteritis rapidly
      regressed under prostacyclin therapy. Such vascular manifestations are frequent
      in testicular carcinoma, but they usually develop after chemotherapy. To our
      knowledge, this is the first case where they preceded the diagnosis and specific
      treatment of a tumour of the testis.

PMID- 1387939
TI  - [Disorders of gastric emptying].
AB  - Disorders of gastric emptying are observed in many clinical situations. Their
      symptoms are diverse and correlate poorly with the objective abnormalities of
      gastric emptying. The underlying mechanism consists of abnormalities of basal
      electrical rhythm, fundic compliance, post-prandial antral motricity and, above
      all, antro-pyloro-duodenal co-ordination, associated to varying degrees. Among
      possible causes 3 clinical situations predominate: diabetes mellitus, functional
      gastrointestinal disorders (idiopathic dyspepsia) and sequelae of gastric surgery
      where retention of solids and accelerated evacuation of liquids may coexist in
      the same patient. Treatment of gastric incontinence rests, almost exclusively, on
      dietary measures, but several drugs, such as metoclopramide, domperidone and
      cisapride, are available to treat gastric stasis. Other compounds, notably
      motilin agonists (erythromycin and its derivatives) are currently being evaluated
      and will reinforce this therapeutic armentarium in a not too distant future.

PMID- 1387940
TI  - [Surgical treatment of pneumothorax by video-thoracoscopy].
AB  - Between May and December 1991, 12 patients with spontaneous pneumothorax were
      treated surgically, using video-thoracoscopy. With this technique bullous lesions
      could be excised in 10 cases and pleurodesis could be performed in all patients.
      Morbidity and mortality were nil. The cosmetic and functional advantages of video
      thoracoscopy were obvious. Long-term results remain to be evaluated. This
      technique has shown that it is possible in all cases to create pleurodesis
      (pleural poudrage or pleurectomy) and to treat parenchymatous lesions (excision
      of bullous systems). This suggests that the long-term results will be the same as
      those obtained with conventional surgery.

PMID- 1387942
TI  - [Surgical treatment of gastroesophageal reflux by celioscopy in children].

PMID- 1387941
TI  - [Association of leishmaniasis and bone marrow toxoplasmosis in HIV-1 infection].

PMID- 1387943
TI  - [Can the course of typhoid fever be predicted?].

PMID- 1387944
TI  - [CA 125 elevation in pleural effusion].

PMID- 1387945
TI  - [Lung abscess caused by Rhodococcus equi in HIV infection: two cases].

PMID- 1387946
TI  - [Two particular aspects of Rhodococcus equi infection: malacoplakia and
      acquisition of resistance to antibiotics].

PMID- 1387947
TI  - [Role of vanadium in the treatment of diabetes mellitus. Experimental data and
      clinical applications].

PMID- 1387948
TI  - [Asymptomatic carriage of Chlamydia trachomatis in men consulting for condylomata
      acuminata].
AB  - A search for Chlamydia trachomatis by cell culture was carried out in the urethra
      of 82 male patients consulting for condyloma acuminata at the Clinical and
      Biological Centre for Sexually Transmissible Diseases of the Saint-Louis
      hospital, Paris. Three patients had discreet urethral signs, but none had
      urethral discharge. Cell culture was positive for C. trachomatis in 36 of the 82
      patients (44 percent). This high prevalence suggests that C. trachomatis should
      systematically be looked for in the urethra of male patients consulting for
      condylomata acuminata. If this cannot be done, then a systematic treatment with
      tetracyclines should be instituted.

PMID- 1387949
TI  - [Food habits of adults in France. Epidemiological data].
AB  - During the year 1990, 43,440 men and women aged from 17 to 69 years accepted to
      fill the NAQA questionnaire (18 items) on feeding habits, as part of a routine
      health examination. The frequency of consumptions and the amounts of food
      consumed are reported here according to sex. Mean energy intake was 2,586 kcal
      for men and 1,758 kcal for women and consisted of: fats 102 and 74 g
      respectively, sucrose 60 and 35 g, proteins 95 and 72 g, alcohol 24 and 4 g,
      calcium 1,128 and 982 mg and cholesterol 457 and 341 mg. For both men and women
      16 percent and 16.8 percent respectively of non-alcohol intakes were made of
      proteins and 38 percent and 38.6 percent of lipids. Calcium intake was low in 7.5
      percent of the subjects. Data analysis by sex and 10-year age groups showed a
      decrease of fats and sucrose rations and stability of protein rations as the
      subjects were growing older. These results were similar to those of a recent
      survey performed with the food history technique. The data obtained by us are an
      interesting source of information for Public Health epidemiology. They are
      compared with those found in the literature and discussed.

PMID- 1387950
TI  - [Incidence of nosocomial infections in a military hospital].
AB  - Over a 2-year period, 479 cases of nosocomial infections were identified in our
      hospital by a surveillance method based on the bacteriological laboratory
      results. The monthly incidence rate ranged from 1.8 to 4 percent of all in
      patients. With this method, a 2 percent background noise and a 4 percent alarm
      threshold could be defined. The most frequent nosocomial infections were urinary
      tract infections (77 percent), purulent skin infections (12 percent) and
      septicaemias (10 percent). Compared during 15 days with the most sensitive
      surveillance method of the National Nosocomial Infections Surveillance System,
      our method proved insufficient to detect nosocomial lung infections and
      superficial surgical wound infections. On the other hand, it was highly
      satisfactory to watch for urinary tract infections and septicaemias. Improvements
      that would not put a heavy burden on the work of clinical departments are
      suggested.

PMID- 1387951
TI  - [Chylous ascites caused by retroperitoneal neoplastic obstruction of lymphatic
      vessels. Treatment by peritoneo-jugular shunt. A case].
AB  - A case of chylous ascites due to retroperitoneal tumoral compression is reported.
      Following failure of a medical treatment which consisted of paracentesis and
      medium-chain triglyceride (MCT) diet, the ascites dried up after installation of
      a peritoneum-jugular vein shunt valve. This operation is seldom performed in
      patients with chylous ascites since the medical treatment with paracenteses, MCT
      diet or even total parenteral nutrition succeeds in drying the effusion in almost
      50 percent of the cases, notably those with postoperative lesion.

PMID- 1387953
TI  - [Pregnant seropositive drug addicts].
AB  - Understanding actual experiences of sexuality and pregnancy in HIV positive drug
      addicts is essential for the prevention of AIDS dissemination. A rigorous
      organization and a coherent therapeutic project are needed for pregnancy
      supervision (pregnancy being carried on in over 50 percent of cases), for
      psychological preparation to the recognition of foetus reality and birth, and for
      newborn follow up to prevent his abandonment. The specific problems of pregnancy,
      seropositivity and drug addiction should be taken into account at the same time.
      The intervention of a voluntary, motivated and polyvalent team and a hospital
      opening towards outreach workers are two essential conditions of success.

PMID- 1387952
TI  - [Isolated atrial fibrillation. The risk of embolism and its prevention].
AB  - Whether or not atrial fibrillation is alone, if not idiopathic, is difficult to
      determine. The risk of embolization in lone atrial fibrillation is distinctly
      higher in healthy subjects over 60 years of age when the left atrium is dilated.
      In chronic atrial fibrillation this risk is higher than in paroxysmal
      fibrillation, especially within the year following the onset of the arrhythmia.
      In most patients anticoagulant therapy is effective in the primary or secondary
      prevention of embolic accidents. In subjects older than 75 aspirin given in daily
      doses of 325 mg seems to give similar results. The risk of antithrombosis therapy
      must not be underevaluated. The alternative is to maintain or restore the sinus
      rhythm, even at an advanced age, if the arrhythmia is recent and the left atrium
      is moderately dilated.

PMID- 1387955
TI  - [Myasthenic crisis after intravenous injection of iodine contrast product].

PMID- 1387954
TI  - [Bromide: an uncommon cause of hyperchloremia].

PMID- 1387956
TI  - [Purpura during Listeria monocytogenes meningoencephalitis].

PMID- 1387957
TI  - [Spontaneous rupture of the splenic artery in an alcoholic diabetic hypertensive
      woman].

PMID- 1387959
TI  - [Lymph node listeriosis in a HIV infected patient].

PMID- 1387958
TI  - [Peri-visceral fat infiltration].

PMID- 1387960
TI  - [Treatment of early scapulohumeral pain by traditional Chinese acupuncture after
      heart surgery].

PMID- 1387961
TI  - Effect of medullary raphe lesions on sexual behavior in male rats with or without
      treatments of p-chlorophenylalanine.
AB  - Male sexual activities were tested in androgen-treated castrated male rats with
      lesions of the raphe obscurus nucleus (ROBL) or lesions of the raphe magnus
      nucleus (RMGL). The ROBL male rats showed low levels of mounting, intromission
      and ejaculation frequencies, and prolonged mount latencies compared to castrated
      and sham-operated control males. The sexual activity in the RMGL group was
      comparable to that of the controls. The results suggest that the raphe obscurus
      nucleus is involved in the neural mechanisms mediating copulatory behavior in
      male rats, and that the raphe magnus nucleus is not. In several castrated control
      and ROBL males, serotonin-synthesis inhibitor, p-chlorophenylalanine (PCPA) was
      injected before the behavioral test, because the raphe obscurus nucleus contains
      a large number of serotonergic neuronal cells. PCPA-treated control males showed
      higher frequencies of copulatory patterns than did control males without PCPA. In
      contrast, the frequencies of ejaculation and intromission were not increased by
      PCPA in the ROBL males, compared to PCPA-untreated ROBL males, although the mount
      latency was shortened and mount frequency was increased. This indicates that PCPA
      facilitates male sexual behavior. However, the suppressive effect of ROBL still
      remained even after deprivation of serotonin. Moreover, PCPA acts on serotonergic
      neurons other than those in the raphe obscurus nucleus, thereby facilitating
      mount activities.

PMID- 1387962
TI  - Exposure to the scent of male mice infected with the protozoan parasite, Eimeria
      vermiformis, induces opioid- and nonopioid-mediated analgesia in female mice.
AB  - The present study examined the nociceptive responses of female mice exposed to
      the scent (soiled cage bedding) of male mice infected with the protozoan
      parasite, Eimeria vermiformis. A 30-min exposure to the odors of a parasitized
      male induced naloxone (1.0 mg/kg)-sensitive opioid-mediated analgesia in female
      mice, whereas a brief 1-min exposure to these odors resulted in a lower
      amplitude, relatively short, nonopioid analgesia that was insensitive to naloxone
      and blocked by the serotonin-1A (5-HT1A), agonist, 8-OH-DPAT. Exposure to the
      odors of nonparasitized males had no significant effects on the nociceptive
      responses of female mice. These results indicate that female mice are able to
      distinguish between the odors of parasitized and nonparasitized male mice, and
      that female mice display both opioid- and nonopioid-mediated aversive responses
      to the odor cues associated with the parasitized males. The implications of these
      findings for parasite-based mate choice are discussed.

PMID- 1387963
TI  - Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin
      5-HT1A (antagonistic) activity.
AB  - The Ki values for etoperidone, trazodone and MCPP (m-chlorophenylpiperazine
      dihydrochloride) at 5-HT1A sites (using rat cerebral cortical synaptosomes and
      [3H]8-OH-DPAT) were determined to be 20.2, 23.6 and 18.9 nM, respectively. In an
      effort to elucidate the functional nature of the interaction at 5-HT1A sites in
      vivo, the ability of each compound to elicit reciprocal forepaw treading (RFT) or
      to block the RFT induced by 8-OH-DPAT in reserpinized rats was tested.
      Specifically, 8-OH-DPAT (1.0 mg/kg SC)-challenged or non-challenged (control)
      reserpinized (1.0 mg/kg SC) rats were administered etoperidone, trazodone or MCPP
      (IP) and scored for the elicitation of RFT (indicative of 5-HT1A agonistic
      activity) or for block of RFT induced by 8-OH-DPAT (indicative of 5-HT1A
      antagonistic activity). Reference compounds confirmed the specificity of the
      test. We report that etoperidone, trazodone and MCPP inhibited 8-OH-DPAT-induced
      RFT (ID50 = 17.4, 23.8 and 13.4 mg/kg, respectively). Only marginal RFT was
      produced in non-challenged animals by etoperidone and trazodone at a high dose
      (40 mg/kg). Taken together, the results suggest a predominant antagonistic
      activity of etoperidone, trazodone and MCPP at 5-HT1A receptor sites in rat
      central nervous system. However, one cannot rule out the possibility that these
      compounds are weak partial agonists. This activity may be relevant to the
      antidepressant action of these compounds.

PMID- 1387966
TI  - The future of laparoscopy in urologic surgery.

PMID- 1387965
TI  - [Isosexual precocious puberty secondary to a subarachnoid cyst].
AB  - A new case of isosexual precocious puberty due to the presence of a subarachnoid
      cyst is reported. A female patient 16 months old was brought to our outpatient
      clinic because she had had two episodes of endometrial bleeding. Activity of the
      hypothalamic-pituitary-ovarian axis was demonstrated by pubertal concentrations
      of LH, FSH and estradiol. An arteriography and a CT demonstrated the presence of
      a subarachnoid cyst which was conditioning the pubertal process. Surgical
      resection of almost all the cyst, along with shunting, did not suppress endocrine
      activity. Suppressive treatment with medroxyprogesterone acetate was prescribed
      in order to accomplish the arrest of the pubertal process.

PMID- 1387964
TI  - MK-801 prevents the enhanced behavioural response to apomorphine elicited by
      repeated electroconvulsive treatment in mice.
AB  - Repeated administration of electroconvulsive stimuli (ECS) to mice once daily for
      a period of 7 days results in an enhanced locomotor response induced by
      apomorphine (1.0 mg/kg, IP). Pretreatment (30 min) with the N-methyl-D-aspartate
      (NMDA) receptor antagonist, MK-801 (0.01-1.0 mg/kg IP), suppressed ECS-induced
      seizure activity in a dose-dependent manner. MK-801 (0.01 and 0.033 mg/kg, IP)
      given 30 min before each ECS dose-dependently decreased apomorphine-mediated
      responses. Administration of MK-801 (0.033 mg/kg IP) 30 min after each convulsion
      had the same effect. These results indicate that MK-801 can abolish the ECS
      induced enhancement of dopamine-mediated behaviour possibly by interfering with
      postictal processes. Thus, NMDA receptors seem to be involved in the behavioural
      changes and presumably also in the neural adaptations produced by repeated ECS.

PMID- 1387967
TI  - Laparoscopic nephrectomy.

PMID- 1387968
TI  - Laparoscopic varicocelectomy.

PMID- 1387969
TI  - Complications of laparoscopy.

PMID- 1387970
TI  - [A team gets in the water].

PMID- 1387971
TI  - Regulation of dynein-driven microtubule sliding by the radial spokes in flagella.
AB  - The regulation of microtubule sliding in flagellar axonemes was studied with the
      use of Chlamydomonas mutants and in vitro assays. Microtubule sliding velocities
      were diminished in axonemes from mutant cells missing radial spoke structures but
      could be restored upon reconstitution with dynein from axonemes with wild-type
      radial spokes. These experiments demonstrate that the radial spokes activate
      dynein's microtubule sliding activity.

PMID- 1387972
TI  - Studies of immune response to hepatitis B vaccine in Thai blood donors.
AB  - The immunogenicity of heat-inactivated plasma derived hepatitis B vaccines were
      studied in one hundred and eighty-two adult blood donor volunteers whose HBV
      markers (HBsAg, anti-HBs) were negative. They were randomized for four regimens
      of 3 micrograms intramuscular Hepaccine-B vaccine at the schedules of 0, 1, 2, 9
      months, 0, 1, 3, 9 months, 0, 2, 6, 12 months, 0, 1, 6, 12 months and another
      regimen of 5 micrograms Hevac-B Pasteur vaccine at 0, 1, 2, 9 months. Blood
      specimens, tested for serological marker (anti-HBs), were drawn at 1, 3, 6, 9, 12
      and 15 months following the initial injection. The outcome revealed that the
      Hepaccine-B vaccinated group in the schedules of 0, 2, 6, 12 and 0, 1, 6, 12
      months yielded seroconversion rates of 48.7% and 56.8%, respectively one month
      after vaccination. After that, the immune response (anti-HBs titer) regularly
      increased every three months until it reached 100% with a geometric mean (GMT) of
      135 and 130 mIU/ml respectively in the fifteenth month. Taking the Hepaccine-B
      and the Hevac-B Pasteur with the same schedule (0, 1, 2, 9 months) into
      consideration, we found that the former yielded the higher seroconversion rate,
      one month after the initial injection, which increased to the highest rate of
      95.8% in the ninth month. After that it was steady until the fifteenth month with
      higher GMT (584 mIU/ml) than that of Hevac-B Pasteur (323 mIU/ml). The
      seroconversion rate of Hevac-B Pasteur in the first month was lower than that of
      Hepaccine-B but it yielded the highest rate of 100% in the sixth month. After
      that, it gradually decreased and again increased to 100% in the fifteenth month.

PMID- 1387973
TI  - A prospective evaluation of preemployment screening methods for acute industrial
      back pain.
AB  - Preemployment screening methods have been ineffective in predicting those at
      risk, and in curbing the impact of back problems in industry. Such methods have
      centered on individual physical factors (capacities and clinical examination).
      This study evaluates commonly used physical examination measures and simple
      historical data for its ability to predict individuals at risk for future back
      injury reporting in the aircraft industry. In this study, once simple historical
      information about previous pain treatment was known, information gained from
      physical factors added no significant predictive value.

PMID- 1387974
TI  - Lumbar disc herniation. Computed tomography scan changes after conservative
      treatment of nerve root compression.
AB  - In 21 patients with computed tomography-diagnosed lumbar herniated nucleus
      pulposus, nerve root pain resolved after conservative treatment. A subsequent
      computed tomography scan was performed 6 months or more after presentation. This
      follow-up computed tomography scan was compared with the initial one. A definite
      decrease in size of the herniated nucleus pulposus was observed in 14 patients:
      disappearance in 5, obvious decrease in 5, and moderate decrease in 4. No
      definite change was observed in seven patients. Major computed tomography scan
      changes occurred significantly more frequently in large herniated nucleus
      pulposus than in small ones (p. less than 0.05). This study suggests that large
      lumbar herniated nucleus pulposus can decrease and even disappear in some
      patients treated successfully with conservative care.

PMID- 1387975
TI  - Functional results after anterior lumbar fusion at L5-S1 in patients with normal
      and abnormal MRI scans.
AB  - The debate continues as to which patient responds best to surgical versus
      nonsurgical intervention for painful degenerative disc syndrome. Discography is
      often used as the basis for that decision. In a review of 53 cases followed for
      an average of 20 months after surgery, only 50% of patients with type I
      (contained) discography and normal magnetic resonance imaging findings were found
      to be improved. In those patients with types II and III (noncontained)
      discography and abnormal magnetic resonance imaging scans, a 75% success rate was
      seen. There was an overall 80% fusion rate for all patients who underwent
      anterior lumbar fusion at L5-S1. Average age was 34 years, with average length of
      disability from low-back pain of 11 months. All patients were placed in a similar
      presurgery and postsurgery rehabilitation protocol and had failed nonsurgical
      treatment options. In this matched group of patients, those with abnormal
      magnetic resonance imaging scans and abnormal discography, clearly fared better,
      with a 75% percent success rate versus 50% success rate in those with normal
      magnetic resonance imaging findings. This series raises the question as to
      whether those patients with normal magnetic resonance imaging findings are
      surgical candidates.

PMID- 1387976
TI  - A modified muscle-splitting approach to the lumbosacral spine.
AB  - A modification of a previously reported extraperitoneal approach to the
      lumbosacral spine is described. The external oblique muscle is split in line with
      its fibers. The anterior and posterior layers of the rectus sheath are divided
      vertically medial to the semilunaris without splitting the internal oblique and
      underlying transversalis abdominus muscles. This allows an extensile
      retroperitoneal approach suitable for exposure of both the mid-lumbar and
      lumbosacral spine. There have been no complications of this approach with its use
      in over 50 patients undergoing anterior lumbar interbody fusion.

PMID- 1387978
TI  - Revision surgery for failed back surgery syndrome.
AB  - Results of surgical treatment in 50 failed back surgery patients were
      retrospectively reviewed to determine what factors influenced surgical outcome.
      Before surgery, all patients had disabling pain and limited function. Overall
      significant improvement in pain and function was obtained in 66% of the patients.
      Thirteen of 16 patients (81%) who had successful fusion of pseudarthrosis had a
      satisfactory outcome, whereas only 3 of 13 patients (23%) who had failed
      pseudarthrosis repair had a satisfactory outcome. Successful pseudarthrosis
      repair is the key to a high clinical success rate in revision surgery for failed
      back surgery syndrome. Pseudarthrosis repair by conventional posterolateral
      fusion with postoperative lumbosacral corset immobilization showed a high failure
      rate. The success rate of reoperation on failed back surgery syndrome patients is
      low.

PMID- 1387977
TI  - Percutaneous laser disc decompression. A new therapeutic modality.
AB  - The authors present a new advance in the treatment of herniated disc disease
      using percutaneous Nd:YAG laser to vaporize a small portion of nucleus pulposus,
      thereby decompressing the disc. In vitro and in vivo animal data are presented.
      Three hundred seventy-seven magnetic resonance imaging or computed tomography
      scan-documented, herniated, nonsequestered lumbar intervertebral discs with
      corresponding clinical findings in 333 patients were so treated in an outpatient
      setting. The longest follow-up was 62 months, with a mean of 26 months. According
      to the Macnab criteria, there was a good to fair response in 261 patients
      (78.4%), and a poor response in 72 (21.6%); 166 patients experienced relief of
      pain during the procedure. One-third of repeat magnetic resonance imaging scans
      at 4-6 months postlaser treatment showed modest to moderate decrease of disc
      herniation.

PMID- 1387979
TI  - Back pain and disability after Harrington rod fusion to the lumbar spine for
      scoliosis.
AB  - Back pain questionnaires were completed by a study group of 103 idiopathic
      scoliosis patients fused with Harrington rods from L3 or lower and a control
      group of 29 patients fused to L2 or above. Minimum time to follow-up examination
      was 2 years. The study group had a higher rate of secondary surgeries for
      complications or late disc disease below the fusion, a higher back pain score,
      more difficulties with normal daily activities, needed more regular pain
      medications, and had more episodes of back pain. Patients older than 30 years at
      surgery had more of these problems if fused to L3 or more caudally. The amount of
      remaining lumbar lordosis correlated significantly with the difficulty of normal
      daily activities.

PMID- 1387980
TI  - [Effect of the tumor cell associated glycoconjugate (TCA) derived Kato III, human
      gastric cancer cells on autologous mixed lymphocyte reaction in patients with
      rheumatoid arthritis].
AB  - We have been developing a new treatment for patients with rheumatoid arthritis
      (RA) by using intradermal injection of carbohydrate molecule complex. Among them,
      tumor cell associated glycoconjugate (TCA), the membrane structure of Kato III is
      one of the effective molecules. We studied the immunomodulatory effect of TCA on
      the autologous mixed lymphocyte reaction (AMLR) using PWM-mitogen induced
      lymphoblasts as stimulator cells and peripheral blood mononuclear cells (PBMC) as
      responder cells. In the kinetic study of the AMLR, its maximum proliferation was
      observed on days five through seven and responding CD4 cells highly expressed HLA
      DR antigen. Studied AMLR in 10 patients with RA, proliferative responses of AMLR
      in these patients were divided into two types, high and low AMLR types. In vitro
      examination of TCA on AMLR showed that TCA at a concentration of 250 ng/ml
      significantly suppressed the AMLR response (p less than 0.01, paired T-test) and
      this phenomenon was found more frequently in high AMLR type patients than in low
      AMLR type patients. The suppressive effect of TCA on AMLR had a tendency to
      correlate with the efficacy of TCA therapy in patients studied. These results
      suggest that TCA may play a role in regulating the function of autoreactive
      lymphocytes of patients with RA.

PMID- 1387981
TI  - Disability beneficiaries who work and their experience under program work
      incentives.
AB  - This research examines the return to work by Disability Insurance beneficiaries
      who were first entitled to benefits in 1980-81 and who were originally selected
      to be interviewed in the New Beneficiary Survey. To facilitate an examination of
      actual labor-force participation by beneficiaries, information on work and
      participation in program work incentives was collected from their claims folders.
      The analysis shows that approximately 10 percent of disability beneficiaries work
      during their initial period of benefit entitlement. About 80 percent are granted
      a trial work period, and over 70 percent of those granted trial work successfully
      complete it. More than half of them, however, were not successful in leaving the
      rolls through their work effort. In fact, benefit terminations due to work
      occurred for fewer than 3 percent of all beneficiaries in the cohort;
      approximately one-third of them had returned to the rolls by the end of the
      period under study. Beneficiaries most likely to make a work attempt were young
      and had a high level of education. Those with a high Social Security benefit
      amount were less likely to make a work attempt.

PMID- 1387982
TI  - Children receiving SSI payments, December 1991.

PMID- 1387983
TI  - [The assessment of the health of industrial enterprise workers and the means for
      its strengthening].
AB  - The authors provide the results of a sociological interview of the collective of
      a mixed feed plant. The interview concerned information about health, healthy way
      of life and routine behavior. Noticeable differences were revealed between the
      theoretical background of the respondents and daily routine. A rapid method was
      employed to objectively evaluate the level of the physical health status. A
      considerable percentage of subjects with low health status were detected. This
      requires carrying out of the goal-oriented treatment, prophylactic and
      organizational measures at the plant.

PMID- 1387984
TI  - [An analysis of the factors affecting the efficacy of prevention programs].
AB  - Methods of multidimensional analysis were used to assay the significance of the
      physiological and behavioral characteristics of the population of the able-bodied
      men of the city of Minsk as regards the efficacy of interventions carried out. It
      has been shown that the population takes a more active part in the implementation
      of measures of conventionally medical nature. Deviations in the health status and
      physiological characteristics revealed by screening favour a more careful
      attitude to the performance of the recommendations made. The low social status
      and the presence of pronounced harmful habits are significant predictors of a
      negative attitude towards preventive interventions.

PMID- 1387985
TI  - [The training of family physicians].

PMID- 1387986
TI  - [Experience in evaluating the professional skills of interns in the outpatient
      office visit].
AB  - The author describes a method of the control over the occupational skills of the
      trainees during outpatient reception with the use of a special chart filled in by
      the expert teacher. The chart allows one to assess the level of knowledge and
      skills, to analyze the performance of the occupational skills in all the students
      of the course, to detect the level of the practical training in disease entities
      and to evaluate the degree of its correspondence with the requirements to be met
      by the physicians of a polyclinic. The results of the 3-year observations over
      the dynamics of the effectiveness of the occupational skills performed and other
      actions with respect to polyclinical therapy, during medical practice and
      attestation are provided.

PMID- 1387987
TI  - [The efficacy of a program of arterial hypertension prevention among an organized
      population (the results of a 5-year observation)].
AB  - An epidemiological examination of 4323 motor transport workers made according to
      the program of the All-Union Cardiology Research Center, USSR AMS, revealed high
      arterial pressure (AP) in 22.6% of cases. The knowledge of hypertension was found
      to be low (34%) as was the coverage with hypotensive treatment (7.1%) and the
      efficacy of the latter one (1.8%). The follow-up studies (for 5 years)
      demonstrated the efficacy of non-medicamentous and medicamentous AP control
      exercised in motor transport workers. It was proved that in the principle AP
      might adequately be decreased and maintained for a long time at the safe level in
      the overwhelming majority of subjects with AP.

PMID- 1387988
TI  - [An increase in the knowledgeability of the population on the problem of arterial
      hypertension as a result of conducting a secondary prevention program in a
      nonorganized rural population].
AB  - The paper is concerned with evaluating the efficacy of sanitary and health
      measures carried out within the framework of the program of secondary prophylaxis
      of arterial hypertension (AH) in an open rural population in terms of changes in
      the information of the community about hypertension. The program included regular
      radio transmissions, talks and lectures pertaining to the problems of essential
      hypertension prevention and treatment. During 4 years, the information of the
      respondents about hypertensive action of table salt increased 4-fold (from 8 to
      32.3%), especially among persons suffering from AH. The number of persons who
      referred to overweight as one of AH causes rose 6-fold (from 2.6 to 18.1%). The
      information did not depend on the sex, age, or the presence of hypertensive
      factors in the examinees. Alterations were recorded in the attitude of the
      examinees to AH and its treatment: the portion of those who took hypotensive
      drugs increased more than 2-fold (from 10.9 to 23.4%) whereas the percentage of
      subjects treated successfully from 6.8 to 10.1%. The data obtained attest to a
      high enough efficacy of sanitary and health measures in relation to AH in the
      rural population.

PMID- 1387989
TI  - [The organization of disability prevention among hypertension patients].
AB  - A study was made of the causes and factors that determine disability in 102 able
      bodied patients suffering from essential hypertension (a random sample), who were
      acknowledged invalids for the first time in 1989. Analysis of the shortcomings in
      the organization of the treatment and prophylactic aid to the population made it
      possible to outline the main trends in disability prevention in patients
      suffering from essential hypertension.

PMID- 1387990
TI  - [Myocardial infarct in motor transport drivers and the results of long-term
      observations].
AB  - As many as 283 drivers with a history of acute myocardial infarction were
      examined. In the long-term postinfarction period, the number of the able-bodied
      accounted for 22.8%, the number of persons with restricted work fitness was
      43.3%, that of the disabled amounted to 33.9%. It should be noted that about 60%
      of the able-bodied and those with restricted work fitness returned to the driving
      related work. However, in some cases, the type of the trucking was either changed
      of the work scope was to be minimized. Criteria forming the basis for predicting
      the recovery of work fitness of the drivers were as follows: non-transmural
      character of myocardial infarction for the most part, the effective staged
      rehabilitation program, positive dynamics and smoothing of the ECG signs of
      myocardial infarction, the lack of areas of regional hypo- and akinesia of the
      myocardium, normalization of the ejection fraction, high and mean indicators of
      physical work fitness, exercise tolerance, coronary reserves, functional class I
      and II angina pectoris of effort, either the lack or initial clinical signs of
      circulatory failure, psychological readaptation, high occupational class, and
      labour orientation.

PMID- 1387991
TI  - [Amyloidosis in the autopsy data from a general hospital of Leningrad].
AB  - Over the recent 20 years the incidence of amyloidosis did not undergo any
      noticeable changes, accounting for 1.48% of the total number of autopsies in 1964
      1968 and for 1.52% in 1984-1988 (P less than 0.5). The number of cases of the
      clinically unrecognized amyloidosis increased from 37.5% in the first period to
      52.18% in the second one. In most cases amyloidosis affects the kidneys (94.9%),
      spleen (58.2%), liver (48%) and then, in the descending order, there follow
      adrenals, intestine, heart, pancreas and other organs (the total data for both
      the periods).

PMID- 1387993
TI  - Euglobulin clot lysis induced by tissue-type plasminogen activator is reduced in
      subjects with increased levels of lipoprotein (a).
AB  - Several reports have evaluated the in vitro effect of lipoprotein(a) [Lp(a)]
      levels on the fibrinolytic system, suggesting that high Lp(a) levels may inhibit
      fibrinolysis by competing for plasminogen binding in different systems. We have
      studied plasminogen activation induced by tissue-type plasminogen activator (t
      PA), as well as other fibrinolytic parameters, in 25 subjects with Lp(a) levels
      greater than 30 mg/dl and the results were compared with those found in 23
      subjects with Lp(a) less than 30 mg/dl. Both groups were similar in age, sex
      distribution, living habits and lipid pattern. Plasminogen activation, when
      measured by t-PA-induced euglobulin clot lysis, was significantly decreased in
      the group with elevated Lp(a) levels (lysis time, 16.7 +/- 3.3 min) compared with
      the group with low Lp(a) levels (11.8 +/- 2.0 min), although 8 of the 25 subjects
      with high Lp(a) levels showed plasminogen activation within the range of the
      control group. A positive significant correlation between Lp(a) levels and t-PA
      induced euglobulin clot lysis time was found. No statistical differences were
      demonstrated between groups for the other fibrinolytic parameters studied.
      Addition of purified Lp(a) to the euglobulin fraction or to plasma resulted in a
      decrease in euglobulin clot lysis. The present study shows that t-PA induced
      plasminogen activation is decreased in individuals with high circulating levels
      of Lp(a) supporting the hypothesis that Lp(a) may interfere with the
      physiological functions of plasminogen.

PMID- 1387992
TI  - [Acute hepatitis associated with etodolac therapy].

PMID- 1387994
TI  - [The mechanisms linking fever and immune reactions].

PMID- 1387995
TI  - [The distribution of dopamine D1 and D2 receptors in the brain of rodents and
      carnivores].
AB  - Studies have been made on the density of receptors and dissociation constants for
      dopamine D1- and D2-receptors in the striatum, n. accumbens with the olfactory
      tubercles and in the frontal cortex of Wistar rats, Norway rats and silver foxes.
      D1 binding was found to be significantly higher than D2 one in all the analysed
      brain structures of the animals studied, especially in the striatum. Although the
      analysis of D1- and D2-receptor binding kinetics revealed differences in Wistar
      and Norway rats, more significant differences were found between rats and silver
      foxes.

PMID- 1387996
TI  - Myocardial technetium-99m-pyrophosphate scintigraphy and echocardiography in the
      diagnosis of cardiac amyloidosis.

PMID- 1387997
TI  - [Experience with laparoscopic nephrectomy].
AB  - Laparoscopic procedures are promising techniques which allow less invasive
      surgery not only for intra-abdominal organs but also for retroperitoneal organs.
      Laparoscopic nephrectomy was first described by Clayman et al. We removed the
      left kidney of a 36-year-old male patient using laparoscopic procedures according
      to Clayman's technique. The kidney had developed hydronephrosis due to congenital
      ureteropelvic junction stenosis. In the peritoneal cavity the freed kidney was
      pushed into a Lapsac, minced using scissors and forceps, and removed without
      elongation of the wound. During the operation, pneumoperitoneum with CO2 gas
      induced increases in PaCO2, central venous pressure, pulmonary artery wedge
      pressure and cardiac output, all of which the patient tolerated well. The patient
      was discharged from the hospital on the 9th postoperative day. Laparoscopic
      nephrectomy is a useful alternative to the conventional open surgery in selected
      cases, when surgical techniques and instruments are improved appropriately.

PMID- 1387999
TI  - Phase II trial for the evaluation of trimetrexate in patients with inoperable
      squamous carcinoma of the esophagus.
AB  - EST 2287 was a Phase II clinical trial conducted by the Eastern Cooperative
      Oncology Group (ECOG) designed to evaluate trimetrexate in patients with
      advanced, measurable, inoperable squamous cell carcinoma of the esophagus. The
      drug was given at a dose of 12 mg/m2 daily for 5 days every 21 days to patients
      with carcinoma of the esophagus. The purpose of this study was to evaluate
      treatment efficacy in terms of tumor response and to assess the toxicity.
      According to a two-stage stopping rule, the study closed after 15 patients had
      entered. There were no responses to treatment, and median survival from study
      entry was 4.3 months. There was one treatment-related death caused by infection.
      One patient experienced life-threatening hematologic toxicity. Overall severe or
      worse toxicity occurred in more than half of the patients. It is concluded that
      additional trials of trimetrexate at this dose and schedule in patients with
      carcinoma of the esophagus are not warranted.

PMID- 1387998
TI  - Benzoyl peroxide.

PMID- 1388000
TI  - Stability of ondansetron hydrochloride in injectable solutions at -20, 5, and 25
      degrees C.
AB  - The stability of ondansetron hydrochloride in 5% dextrose injection and in 0.9%
      sodium chloride injection when stored frozen, refrigerated, and at room
      temperature was studied. Solutions of ondansetron 0.03 and 0.3 mg/mL (as the
      hydrochloride salt) were prepared by adding 1.5 or 15 mg of the drug to 50-mL
      minibags containing 5% dextrose injection or 0.9% sodium chloride injection. All
      solutions were prepared in triplicate, and each container was tested in
      duplicate. Testing at the time of preparation and at each subsequent test
      interval included visual inspection of color and clarity, determination of pH,
      and a stability-indicating high-performance liquid chromatographic assay to
      measure the ondansetron concentration. Conditions assessed included storage at 
      20 degrees C for two weeks to three months, 5 degrees C for 7-14 days,
      approximately 25 degrees C for up to 48 hours, and various combinations of these
      conditions. The concentration of ondansetron in each solution remained above 90%
      of the original concentration at each observation time under all storage
      conditions. No changes in color or clarity were observed, and there were only
      minor changes in pH. Ondansetron 0.03 and 0.3 mg/mL in 5% dextrose injection or
      0.9% sodium chloride injection was stable when stored (1) for up to three months
      at -20 degrees C, followed by up to 14 days at 5 degrees C and by 48 hours at 25
      degrees C and (2) for up to 14 days at 5 degrees C, followed by up to 48 hours at
      25 degrees C.

PMID- 1388001
TI  - Desensitization to allopurinol in patients with gout and cutaneous reactions.
AB  - PURPOSE: To determine the efficacy and safety of slow oral desensitization in the
      management of allopurinol-related pruritic cutaneous eruptions. PATIENTS AND
      METHODS: Nine patients with renal insufficiency and chronic tophaceous gouty
      arthritis, who had to interrupt their allopurinol therapy because of an allergic
      type pruritic maculopapular eruption, were enrolled in an allopurinol oral
      desensitization protocol using a schedule of gradually increasing doses. RESULTS:
      Cautious reinstitution of allopurinol was successfully accomplished in all nine
      patients, but four individuals required dose adjustment because of development of
      a mild, recurrent, macular rash early during the protocol at allopurinol doses of
      less than or equal to 5 mg/d. Transient, postdesensitization cutaneous reactions
      occurred in two patients, one of whom also had an early rash. CONCLUSION: Oral
      desensitization to the minor rashes induced by allopurinol is a feasible and
      acceptably safe approach to therapy, particularly for those with renal
      insufficiency in whom no substitute urate-lowering drug is available.

PMID- 1388002
TI  - Epidemiology of small bowel bacterial overgrowth and rice carbohydrate
      malabsorption in Burmese (Myanmar) village children.
AB  - Breath hydrogen tests were performed after a rice meal (3 g of cooked rice/kg of
      body weight, equivalent to 1 g of carbohydrate/kg of body weight) on 256 village
      children (age range 1-59 months) who were known hydrogen (H2) producers.
      Anthropometric measurements were made every three months and growth rates were
      calculated. A breath H2 excretion pattern that suggested small bowel bacterial
      overgrowth (SBBO), which was recognized as a transient maximum level of 10 ppm or
      more at 20-, 40-, or 60-min breath samples following the rice meal, was present
      in 53 (20.7%) children, and was more frequent in children 36-47 and 48-59 months
      old. This breath H2 excretion pattern was detected in 48 (33.3%) of 144 children
      who were rice malabsorbers (greater than 10 ppm H2 above baseline values in one
      of the breath samples taken between 90 and 240 min), and in only five (4.5%) of
      112 rice absorbers. Children who had SBBO had a high relative risk (10.7) of
      being rice malabsorbers. Rice malabsorbers have a high relative risk (59.7) of
      having faltered growth, accompanied by a large etiologic fraction (94%). This
      same risk (6.68) and an etiologic fraction of 62% exist in children with
      untreated SBBO. These findings emphasize the need for interventions aimed at
      reducing the prevalence of SBBO or similar conditions as detected by the breath
      H2 excretion pattern to prevent rice malabsorption and growth faltering.

PMID- 1388003
TI  - Preoperative rectal indomethacin for analgesia after laparoscopic sterilisation.
AB  - A randomised, double-blind, placebo-controlled study was conducted among 56 day
      case patients to determine the effect of the preoperative administration of
      rectal indomethacin on postoperative pain and opioid requirements after
      laparoscopic sterilisation. Outcome in women receiving indomethacin did not
      differ significantly from the placebo group, but there was a trend to lower
      subjective pain scores, reduction in early postoperative pain assessed
      objectively and lower parenteral pethidine requirements in the first three hours
      postoperatively. Indomethacin did not appear either to cause side-effects or to
      significantly reduce morbidity from the other postoperative sequelae of
      laparoscopy. Despite evidence for postoperative analgesic effect, the clinical
      benefits of premedication with rectal indomethacin were minor.

PMID- 1388004
TI  - Effects of a thromboxane synthetase inhibitor on established immune complex
      glomerulonephritis in dogs.
AB  - Twelve Beagles were inoculated with concanavalin A, and after a mean ninefold
      increase in antibody titer, 1 mg of concanavalin A was infused into each renal
      artery of each dog to induce in situ immune complex glomerulonephritis. Starting
      4 weeks after renal arterial infusion, 6 dogs were treated orally 3 times daily
      with 30 mg of 3-methyl-2 (3 pyridyl)-1-indolectanoic acid (CGS 12970)/kg of body
      weight, a thromboxane synthetase inhibitor, and 6 dogs (control group) received a
      gelatin capsule 3 times daily. Endogenous creatinine clearance and 24-hour
      urinary excretion of protein and thromboxane B2 were determined for each dog
      prior to renal arterial infusion, at the initiation of treatment and at 2, 4, 6,
      and 8 weeks after initiation of treatment. In addition, methyoxy-3H inulin
      clearance was determined at initiation of treatment and 4 and 8 weeks later.
      Renal specimens were examined histologically at the initiation of treatment and 4
      and 8 weeks later. Glomerular mononuclear profiles/microns 3 were determined from
      at least 10 equatorially sectioned glomeruli from each dog. Paired t tests were
      used to compare mean values at the various time points to the respective mean
      baseline value and 2-sample t tests were used to evaluate differences between
      treatment groups. At the start of treatment (4 weeks after renal arterial
      infusion of concanavalin A), histologic evaluation of renal specimens revealed
      glomerular epithelial crescent formation, mononuclear cell proliferation, and
      infiltration of neutrophils. Mononuclear cell profiles and urinary excretion of
      protein and thromboxane B2 were significantly increased, but endogenous
      creatinine clearance values were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388005
TI  - Effect of intra-abdominal pressure on abdominal wall blood flow.
AB  - Adverse effects of increased intra-abdominal pressure (IAP) on cardiac,
      pulmonary, and renal function have been well described. Abdominal wound healing
      complications seen in the massively injured patient may also be associated with
      IAP. The effects of IAP on abdominal wall blood flow, however, have not been
      documented. This study examines rectus sheath (RS) blood flow in a porcine model
      of increased IAP. Seven domestic swine were anesthetized with pentobarbital and
      maintained with isoflurane. Swan-Ganz and femoral arterial catheters were placed
      for measurement of mean arterial pressure (MAP), cardiac output (CO), and
      pulmonary capillary wedge pressure (PCWP). A midline incision was performed for
      placement of laser flow probe on the RS and for placement of catheters to raise
      and measure IAP. Intra-abdominal pressure was then increased by installation of
      lactated ringers (LRs) into the peritoneum. Mean arterial pressure was maintained
      throughout the procedure with intravenous LR. Hemodynamics and RS blood flow data
      were obtained at baseline, 10, 20, 30, and 40 mm Hg IAP. Analysis of data was
      done by paired t-test with level of significance at P less than 0.05 and linear
      regression. Rectus sheath blood flow was significantly reduced at all pressure
      levels when compared to baseline and negatively correlated (r = -0.82) with
      increasing IAP. Since indices of systemic perfusion were maintained with
      increasing IAP, the decreased RS blood flow is most likely due to increased
      compartmental pressure within the abdomen.

PMID- 1388006
TI  - Spinal manipulation for low-back pain.
AB  - PURPOSE: To review the use, complications, and efficacy of spinal manipulation as
      a treatment for low-back pain. DATA IDENTIFICATION: Articles were identified
      through a MEDLINE search, review of articles' bibliographies, and advice from
      expert orthopedists and chiropractors. STUDY SELECTION: All studies reporting use
      and complications of spinal manipulation and all controlled trials of the
      efficacy of spinal manipulation were analyzed. Fifty-eight articles, including 25
      controlled trials, were retrieved. DATA ANALYSIS: Data on the use and
      complications of spinal manipulation were summarized. Controlled trials of
      efficacy were critically appraised for study quality. Data from nine studies were
      combined using the confidence profile method of meta-analysis to estimate the
      effect of spinal manipulation on patients' pain and functional outcomes. RESULTS
      OF DATA SYNTHESIS: Chiropractors provide most of the manipulative therapy used in
      the United States for patients with low-back pain. Serious complications of
      lumbar manipulation, including paraplegia and death, have been reported. Although
      the occurrence rate of these complications is unknown, it is probably low. For
      patients with uncomplicated, acute low-back pain, the difference in probability
      of recovery at 3 weeks favoring treatment with spinal manipulation is 0.17 (for
      example, increase in recovery from 50% to 67%; 95% probability limits of
      estimate, 0.07 to 0.28). For patients with low-back pain and sciatic nerve
      irritation, the difference in probabilities of recovery at 4 weeks is 0.098
      (probability limits, -0.016 to 0.209). CONCLUSIONS: Spinal manipulation is of
      short-term benefit in some patients, particularly those with uncomplicated, acute
      low-back pain. Data are insufficient concerning the efficacy of spinal
      manipulation for chronic low-back pain.

PMID- 1388007
TI  - [Type 1 herpesvirus cutaneo-mucous infection resistant to aciclovir in a HIV
      infected patient. Clinical and virological study].

PMID- 1388008
TI  - Lymphocyte subset changes in persons infected with human immunodeficiency virus.
AB  - The severe complications of the acquired immunodeficiency syndrome represent the
      final phase of a prolonged course of immune system destruction during the
      infection by human immunodeficiency virus (HIV). Many of these complications can
      be predicted by measuring the depletion of CD4 positive lymphocytes. The CD4
      positive lymphocyte counts are now widely accepted as a surrogate marker to
      assess the stage of disease and to determine immune response in major clinical
      trials. Other lymphocyte subsets are candidate surrogate markers for
      antiretroviral therapy. Our laboratory has utilized flow cytometry to perform
      lymphocyte subset testing, including CD4, CD8, CD4/CD8 ratio, and others for more
      than three years on persons with suspected immune deficiency. Results from our
      laboratory are presented to illustrate the use of these procedures in an urban,
      predominantly inner city population. The role of flow cytometry in monitoring
      patients with HIV infection is discussed.

PMID- 1388009
TI  - Immunological techniques to differentiate lymphoma from other malignancies.
AB  - Seven patients, who had lymph nodes or masses examined by both immunoperoxidase
      staining and flow cytometry, are presented to illustrate the value of each
      technique including a critical analysis of the current application of these
      techniques in the pathology laboratory. All seven patients had diagnoses
      established by immunoperoxidase staining using antibodies directed against:
      Leukocyte Common Antigen (LCA), Epithelial Membrane Antigen (EMA), Neuron
      Specific Enolase (NSE), Leu M1, B4 or chromagrafin and synaptosin. Flow
      cytometry, which could be more rapidly performed, when sufficient cells could be
      separated from the node or mass, was diagnostic in two of the seven cases. Flow
      cytometry failed to show abnormalities in Hodgkin's disease or solid tumors, but
      it was useful in rapid diagnosis of lymphoma, provided that the sample contained
      mostly involved tissue. Nodes in which there was a minor infiltration with
      lymphoma cells could only be detected by immunoperoxidase technique.

PMID- 1388010
TI  - Tributyltin increases cytosolic free Ca2+ concentration in thymocytes by
      mobilizing intracellular Ca2+, activating a Ca2+ entry pathway, and inhibiting
      Ca2+ efflux.
AB  - The immunotoxic environmental pollutant tri-n-butyltin (TBT) kills thymocytes by
      apoptosis through a mechanism that requires an increase in intracellular Ca2+
      concentration. The addition of TBT (EC50 = 2 microM) to fura-2-loaded rat
      thymocytes resulted in a rapid and sustained increase in the cytosolic free Ca2+
      concentration ([Ca2+]i) to greater than 1 microM. In nominally Ca(2+)-free
      medium, TBT slightly but consistently increased thymocyte [Ca2+]i by about 0.11
      microM. The subsequent restoration of CaCl2 to the medium resulted in a sustained
      overshoot in [Ca2+]i; similarly, the addition of MnCl2 produced a rapid decrease
      in the intracellular fura-2 fluorescence in thymocytes exposed to TBT. The rates
      of Ca2+ and Mn2+ entry stimulated by TBT were essentially identical to the rates
      stimulated by 2,5-di-(tert.-butyl)-1,4-benzohydroquinone (tBuBHQ), which has
      previously been shown to empty the agonist-sensitive endoplasmic reticular Ca2+
      store and to stimulate subsequent Ca2+ influx by a capacitative mechanism. The
      addition of excess [ethylenebis(oxyethylenenitrilo)]tetraacetic acid to
      thymocytes produced a rapid return to basal [Ca2+]i after tBuBHQ treatment but a
      similar rapid return to basal [Ca2+]i was not observed after TBT treatment. In
      addition, TBT produced a marked inhibition of both Ca2+ efflux from the cells and
      the plasma membrane Ca(2+)-ATPase activity. Also, TBT treatment resulted in a
      rapid decrease in thymocyte ATP level. Taken together, our results show that TBT
      increases [Ca2+]i in thymocytes by the combination of intracellular Ca2+
      mobilization, stimulation of Ca2+ entry, and inhibition of the Ca2+ efflux
      process. Furthermore, the ability of TBT to apparently mobilize the tBuBHQ
      sensitive intracellular Ca2+ store followed by Ca2+ and Mn2+ entry suggests that
      the TBT-induced [Ca2+]i increase involves a capacitative type of Ca2+ entry.

PMID- 1388011
TI  - Phospholipid binding of annexin V: effects of calcium and membrane
      phosphatidylserine content.
AB  - We studied the binding of fluorescein-labeled annexin V (placental anticoagulant
      protein I) to small unilamellar phospholipid vesicles at 0.15 M ionic strength as
      a function of calcium concentration and membrane phosphatidylserine (PS) content.
      As the mole percentage of PS in the membrane increased from 10 to 50%, the
      stoichiometry of binding decreased hyperbolically from 1100 mol phospholipid/mol
      annexin V to a limiting value of 84 mol/mol for measurements made at 1.2 mM
      CaCl2. Over the same range of PS content, Kd remained approximately constant at
      0.036 +/- 0.011 nM. A similar hyperbolic decrease in stoichiometry was observed
      with vesicles containing 10 or 20% PS when the calcium concentration was
      increased from 0.4 to 10 mM. Thus, the density of membrane binding sites is
      strongly dependent on the membrane PS content and calcium concentration. The
      effect of calcium on annexin V-membrane binding is proposed to be due to the
      formation of phospholipid-calcium complexes, to which the protein binds, rather
      than to an allosteric effect of calcium on protein-phospholipid affinity.

PMID- 1388012
TI  - Dinitrophenyl S-glutathione ATPase purified from human muscle catalyzes ATP
      hydrolysis in the presence of leukotrienes.
AB  - Dinitrophenyl S-glutathione (Dnp-SG) ATPase has been purified from human muscle
      to apparent homogeneity using Dnp-SG affinity chromatography and immunoaffinity
      chromatography using antibodies raised against human erythrocyte Dnp-SG ATPase.
      The enzyme purified from human muscle showed a subunit M(r) value of about 38 kDa
      in denaturing gels. The M(r) value of the native enzyme as determined by Sephadex
      G-200 gel filtration was found to be about 80 kDa, which indicates that it is a
      dimer. The N-terminus of the enzyme was blocked. Its immunological and kinetic
      properties were similar to Dnp-SG ATPase of human erythrocytes. Besides
      catalyzing the ATP hydrolysis in the presence of Dnp-SG, the muscle enzyme also
      catalyzed ATP hydrolysis in the presence of various leukotrienes, namely
      LTC4.LTD4, LTE4, and N-acetyl LTE4. The specific activity of the enzyme toward
      LTC4 was relatively higher than other GSH-xenobiotic conjugates. The muscle
      enzyme exhibits a low Km value for all leukotrienes as compared to Dnp-SG,
      indicating high affinity of the enzyme for leukotrienes as activators. The enzyme
      also catalyzed ATP hydrolysis in the presence of GSH conjugates of endogenously
      generated fatty acid epoxides. Our results might suggest that Dnp-SG ATPase is
      involved in the transport of GSH conjugates, leukotrienes, and other organic
      anions in muscle, erythrocytes, liver, and probably other tissues.

PMID- 1388013
TI  - Different susceptibility of red cell membrane proteins to calpain degradation.
AB  - The presence of low levels of calpastatin activity in erythrocytes of
      hypertensive rats affects regulation of calpain activity so it is highly
      susceptible to activation within physiological fluctuations in [Ca2+]. Under
      identical conditions, in red cells of normotensive rats, calpain activation is
      efficiently controlled by the high levels of calpastatin activity, and a
      progressive increase in proteinase activity can only be observed in parallel with
      a decrease in the level of calpastatin. In intact erythrocytes from hypertensive
      rats exposed to small variations in [Ca2+], degradation of anion transport
      protein (band 3) and Ca(2+)-ATPase appears as a primary event indicating that
      these two transmembrane proteins are probably early recognized as targets of
      intracellular calpain activity. Furthermore, band 3 protein seems to be
      structurally modified in erythrocytes from hypertensive rats, as indicated by its
      increased susceptibility to degradation in the presence of 10-50 microM Ca2+. In
      addition, when exposed to progressive and limited increases in [Ca2+],
      erythrocytes from hypertensive rats, but not those from normotensive rats, show a
      high degree of fragility that can be restored to normal values by inhibition of
      calpain. These results indicate that, within fluctuations in [Ca2+] close to
      physiological values, regulation of calpain activity is efficiently accomplished
      in normal erythrocytes but is completely lost in cells from hypertensive animals.
      Regulation is of critical importance in maintaining normal structural and
      functional properties of selective red cell membrane and cytoskeletal proteins,
      among which band 3 and Ca(2+)-ATPase appear to be the substrates with highest
      susceptibility to digestion by calpain.

PMID- 1388014
TI  - Limb perfusion. An objective measure of hemodynamic improvement after
      angioplasty.
AB  - Forty-four patients undergoing femoropopliteal angioplasty were studied by
      magnetic resonance blood flowmetry to determine quantitative limb perfusion.
      Baseline limb perfusion averaged 0.52 +/- 0.15 mL/min per 100 cc of tissue.
      Perfusion values for successful angioplasties rose within 72 hours to a mean of
      1.40 +/- 0.31 mL/min per 100 cc of tissue. There were five early failures (less
      than 30 days), in which perfusion fell to 0.54 +/- 0.10 mL/min per 100 cc of
      tissue; at 6 months, 12 additional angioplasties had failed, with limb perfusion
      values of 0.68 +/- 0.16 mL/min per 100 cc of tissue. At 6 months, perfusion in
      four additional limbs had decreased to between 0.7 and 1.0 mL/min per 100 cc of
      tissue, with a mean change of 0.59 mL/min per 100 cc of tissue; duplex ultrasound
      imaging at these sites showed restenoses ranging from 50% to 75%. We conclude
      that lower-leg limb perfusion appears to be a reliable measure of hemodynamic
      improvement after femoropopliteal angioplasty and may provide an early indicator
      of impending failure.

PMID- 1388015
TI  - Treatment and outcome of right colon cancers adherent to adjacent organs or the
      abdominal wall.
AB  - Fifty-four (4%) of 1284 patients treated for adenocarcinoma of the colon and
      rectum during a 10-year period ending in 1989 underwent potentially curative
      resection of right colon lesions found during surgery to be adherent to adjacent
      organs, abdominal wall, or retroperitoneum. Final pathologic staging was as
      follows: modified Dukes' class B1 (n = 2), B2 (n = 24), C1 (n = 1), and C2 (n =
      27). Thirteen (24%) patients had postoperative complications, including two
      (3.7%) with sepsis. One patient died after surgery (mortality, 1.9%). Survival
      rates at 1, 3, and 5 years were 74%, 52%, and 37%, respectively. Only one (11%)
      of nine patients with pancreatic or duodenal adherence treated with limited
      resection was free of disease during follow-up. Adjuvant radiation therapy and
      chemotherapy did not improve survival. Histologic depth of tumor penetration
      could not be predicted by intraoperative assessment, and therefore radical
      resection is recommended whenever possible.

PMID- 1388016
TI  - Cloning and sequencing of influenza C/Yamagata/1/88 virus NS gene.
AB  - It was previously shown that the shortest RNA of influenza C/California/78 virus
      contains 934 nucleotides and codes for two nonstructural proteins of 286 amino
      acids (NS 1) and 121 amino acids (NS 2). In this report, we determined the
      nucleotide sequence of the NS gene of the recently isolated influenza
      C/Yamagata/1/88 strain by using cloned cDNA derived from the viral RNA. Compared
      with the NS gene of C/California/78, one nucleotide insertion has occurred in the
      NS gene of C/Yamagata/1/88. This caused frame shifts of both the NS 1 and NS 2
      reading frames, directing the synthesis of the NS 1 and NS 2 proteins consisting
      of 246 and 182 amino acids, respectively.

PMID- 1388017
TI  - The multiple role of cytokines in IgE-mediated allergic reactions.

PMID- 1388018
TI  - Annexin V-crystal structure and its implications on function.
AB  - Annexins constitute a family of cytosolic, water soluble proteins, which bind to
      negatively charged phospholipids in a calcium-dependent manner. They display
      structural and functional features of both soluble and integral membrane
      proteins. The annexins face the hydrophilic as well as the hydrophobic phase
      (Janus-faced proteins) and mediate ion transport in vitro. We present the refined
      structure and molecular model of annexin V at 2.0 A resolution. The molecule is
      almost entirely alpha-helical, and each of the four repeats of annexin V is
      folded into a compact domain of similar structure. The four domains are arranged
      in an almost planar, cyclic array. In the center of the molecule, one can find a
      prominent hydrophilic pore, which we associate with the calcium-selective channel
      found in annexin V. Annexin V has an overall flat, slightly curved shape with two
      faces, one convex and one concave. The three calcium binding sites Ca1 to Ca3,
      all located at the convex face of the molecule, are assumed to be phospholipid
      binding sites, as suggested by their structural similarity to the calcium site of
      phospholipase A2. Soluble and membrane-bound annexin have closely similar
      structures, as shown by electron microscopic analysis. Several other observations
      provide evidence that the membrane-anchoring region of the annexin V molecule is
      located on the convex face. In the last part of this article, the
      electrophysiology of the annexins is described. Ion permeation occurs in discrete
      conductance states and is regulated by voltage across the membrane. A model for
      the annexin V-membrane interaction, the ion channel formation, and the ion
      conduction pathway is proposed.

PMID- 1388019
TI  - Coagulation and fibrinolysis in cancer.
AB  - Haemostasis is a system of finely adjusted interactions between cells, enzymatic
      reaction cascades and inhibitors. Disturbances of this balance occur in many
      disorders, especially in inflammatory processes, septicaemia and cancer. In such
      cases malignant cells and infectious organisms activate the plasmatic enzyme
      cascades, especially of the coagulation and fibrinolysis cascades. The resulting
      consumption and proteolytic degradation of the regulatory proteins contribute to
      hypercoagulability and secondarily to reactive fibrinolysis, and these may then
      lead to local thromboses and haemorrhages. These pathogenic events culminate in
      disseminated intravascular coagulation (DIC), frequently with organ failure and
      death. Factors of both plasmatic systems are also "misused" by malignant cells
      for the purposes of growth and metastasis. Prominent examples of this misuse are
      the formation of a protective fibrin shield against the endogenous defence
      mechanisms and the local degradation of tissues for tumor proliferation as well
      as for cell permeation and invasion. In the search for a potential therapy a
      number of protease inhibitors, predominantly of enzymes of coagulation and
      fibrinolysis, have been tested in vivo with regard to their efficacy. So far,
      however, it has not been possible to find a new uniform treatment principle to
      inhibit the growth and/or metastasis of different types of tumor. The
      haemorrhagic diathesis and thromboses frequently associated with tumors are
      generally treated by substitution with plasma components, especially concentrates
      of coagulation factors and inhibitors.

PMID- 1388020
TI  - Suppression of immune responses by cloned T cells and their products.
AB  - We have established a number of IL-2 dependent T cell clones with a definite
      suppressor function for the antibody response. Our collection included CD4+
      helper (Th) and suppressor T cell (CD4+ Ts), and CD8+ cytotoxic (Tc) and
      suppressor T cell (CD8+ Ts) clones. Ts clones were defined by their suppressive
      activity on antigen-induced proliferative response and on helper functions of
      other CD4+ Th clones without detectable cytotoxicity and production of known
      helper type interleukins. The I-J expression was found to be present on both Th
      and Ts clones, and was generally associated with the H-2 restriction specificity
      of TcR of these clones. We have shown that the activated CD4+ Ts cells could
      inhibit the increase of intracellular Ca2+ of Th clones induced by antigen-pulsed
      antigen-presenting cells (APC). The identity of MHC restriction-specificities was
      required for the instant suppression of Ca2+ influx of Th clones, while a longer
      period of activation of Ts clones was needed to suppress the response of Th
      clones having different MHC restrictions. A strict selectivity was found in the
      suppressive activity of Ts clones in that Ts clones could suppress the Ca2+
      responses of Th1 or Th2 clones but not of other CD4+ Ts clones. Ts clones could
      suppress the Ca2+ influx of Th clones induced only by antigen-pulsed APC or anti
      TcR antibody but not by Con A or IL-2. Both CD4+ and CD8+ Ts clones released
      soluble immunosuppressive factors upon stimulation with immobilized anti-CD3
      antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388021
TI  - The current status of PET scanning with respect to schizophrenia.
AB  - PET scan studies of regional brain energy metabolism in schizophrenia have
      hitherto not been consistent in demonstrating any specific perturbation in
      heterogenous groups of patients. In some studies there was a tendency to reduced
      metabolic values in several regions in chronic patients. The variance of
      metabolic rates also tended to be greater in the group of schizophrenic subjects,
      but rates for most patients overlapped with those of the controls. Studies of
      regional brain energy metabolism also failed to disclose consistent effects of
      clinical antipsychotic drug treatment in schizophrenic patients. PET measurements
      of dopamine receptor functions in the major basal ganglia using different
      radioligands for D2 dopamine receptors also gave inconsistent results. One group
      reporting elevated densities of D2 dopamine receptors in the major basal ganglia
      of drug-naive schizophrenic patients could not be confirmed. PET measurements of
      dopamine receptor binding demonstrated profound and selective effects of clinical
      antipsychotic drug treatment on D2 and D1 dopamine receptor occupancy in
      schizophrenic patients. All chemically different categories of antipsychotic
      drugs induced a substantial occupancy of D2 dopamine receptors in relation to
      clinical treatment. This effect has been shown to be dose dependent and fully
      reversible. It appears much earlier than the antipsychotic effect and it is also
      present in neuroleptic-resistant patients. Accordingly, neuroleptic resistance is
      not related to individual pharmacodynamic or pharmacokinetic factors. Drug
      resistance is in all probability related to heterogeneity of biologic factors
      causing schizophrenia. Some, but not all, of the antipsychotic drugs also induce
      a significant D1 dopamine receptor occupancy. This effect was most marked for the
      unconventional drug clozapine, which showed about the same degree of D1 and D2
      dopamine receptor blockade when given in conventional clinical doses. Further
      refinements of the resolution of PET scan instruments in the years to come and
      the development and application of new tracers will supply powerful tools for the
      further search for fundamental alterations of brain function in schizophrenia.

PMID- 1388022
TI  - Elevated D2 in schizophrenia: role of endogenous dopamine and cerebellum.
      Commentary on "The current status of PET scanning with respect to schizophrenia".

PMID- 1388023
TI  - PET studies of neuroreceptors in schizophrenia. Commentary on "The current status
      of PET scanning with respect to schizophrenia".

PMID- 1388024
TI  - Cloning and characterization of the human muscle phosphofructokinase gene.
AB  - A 35-kbp region of genomic DNA encoding the human muscle phosphofructokinase
      (HPFK-M) gene including all of the coding exons (1-22) plus 2.2-kbp of 5'
      flanking sequence has been cloned. The exon boundaries are the same as has been
      observed for the rabbit muscle phosphofructokinase (RPFK-M), the human liver
      phosphofructokinase (HPFK-L), and the mouse liver phosphofructokinase (MPFK-L)
      genes. Characterization of the structure of the HPFK-M gene and its transcript in
      Epstein-Barr virus transformed B-cell lines derived from patients with glycogen
      storage disease type VII (GSDVII or Tarui's disease) demonstrated that this
      single-copy gene encodes a normal sized 3.0-kb transcript in the four cases
      examined. This suggests the lesion in these cases represents either a point
      mutation or possibly a small insertion or deletion resulting in the synthesis of
      a defective HPFK-M protein. Analysis of the 5'-flanking region demonstrated the
      presence of a functional promoter located within 114 nucleotides of a proposed
      transcription initiation site. This promoter was active in the human cervical
      carcinoma cell line, HeLa S3, the dedifferentiated human hepatoma cell line,
      HepG2.1, and the mouse myoblast cell line, C2C12, suggesting this promoter has a
      broad cell-type specificity. In addition, from the known HPFK-M cDNA sequences,
      this observation indicates that the HPFK-M gene has a second promoter located
      upstream from the genomic region isolated in this study.

PMID- 1388026
TI  - A monoclonal antibody to common acute lymphoblastic leukemia antigen (CALLA) and
      its expression on several human tumor cell lines.
AB  - We describe a newly-made murine monoclonal antibody to the common acute
      lymphoblastic leukemia antigen (CALLA), named SHB-10. The antigen detected by SHB
      10 has a molecular weight of about 105 kDa. This antibody is very similar to that
      of conventional anti-CD10 Ab on indirect flowcytometric analysis using lymphoid
      malignant cell lines and peripheral lymphocytes of acute lymphoblastic leukemia
      (ALL) patients. The binding of anti-CD10 to Daudi cell and peripheral lymphocytes
      of ALL patients is blocked by SHB-10. Thus this monoclonal antibody is thought to
      detect the CALLA. The distribution of antigen detected by SHB-10 on several cell
      lines of neuroectodermal tumor and lymphoid malignancy was analysed and a slight
      difference in their cell surface expression is observed when compared with that
      by conventional anti-CD10. Further biochemical analysis is now under way for a
      better characterization of this antigen.

PMID- 1388025
TI  - Microdialysis measurement of serotonin release in the central nervous system.

PMID- 1388027
TI  - Micromorphological relationship between resin and dentin in vivo and in vitro.
AB  - This study examined the relationship between resin and dentin both in vitro and
      in vivo using phosphoric acid conditioning. Four groups of 10 teeth each had
      standardized Class V preparations made with the gingival cavosurface margin in
      the root. In Group 1, involving freshly extracted teeth, the enamel and dentin
      was conditioned with 37% phosphoric acid gel for 15 seconds. NTG-GMA/PMDM was
      applied to the enamel and dentin followed by an application of BIS-GMA/HEMA and
      restoration with P50. Group 2 served as a control omitting the conditioning step.
      Groups 3 and 4 were treated similarly to Groups 1 and 2 except in vivo and
      extracted 2 weeks after restoration placement. All teeth were sectioned
      longitudinally through the restoration. Impressions were taken of the
      tissue/restoration interface and examined by SEM for disclosure of gaps. The
      teeth were then demineralized and the fitting surface of the restoration was
      examined by SEM for evidence of resin penetration into the tissue. The results
      showed a total absence of gaps both in vitro and in vivo after acid conditioning
      compared to the controls commonly showing gaps. Penetration of resin into the
      dentin to form a zone of diffusion or hybrid layer was observed only in the
      conditioned specimens. The phenomenon was observed both in vivo and in vitro. It
      was concluded that a significant potential exists for phosphoric acid
      conditioning of dentin to promote bonding.

PMID- 1388029
TI  - Follow these steps to rid office from any discriminating practices.

PMID- 1388028
TI  - Who will pay the bills?

PMID- 1388030
TI  - Inhibition of vasopressin and aldosterone release by atrial natriuretic peptide
      in conscious rabbits.
AB  - To elucidate the regulatory role of atrial natriuretic factor (ANF) on
      vasopressin (AVP) and aldosterone release in conscious rabbits, ANF was
      administered systematically at a rate of 15 pmol min-1 (kg body wt)-1 for 15 min
      in two series of experimental animals in which AVP and/or aldosterone production
      was stimulated. In euhydrated rabbits (series I), systemic administration of
      angiotensin II (Ang II) (10 pmol min-1 (kg body wt)-1, 15 min) stimulated
      aldosterone release threefold from basal plasma concentrations (140 pg ml-1). The
      co-application of ANF inhibited the Ang II-induced release of aldosterone without
      influencing the non-stimulated AVP system. In dehydrated rabbits (series II) with
      elevated plasma osmolality and AVP concentration, exogenously applied ANF
      increased plasma ANF fourfold at marginally reduced arterial pressure. Plasma AVP
      concentrations were reduced by 3.4 pg ml-1 (25%) on average, and plasma
      aldosterone concentrations were lowered by 34 pg ml-1 (23%) at unchanged levels
      of plasma corticosterone. Receptor binding studies using [125I]ANF as radioligand
      revealed Ang II-independent high-affinity receptors for ANF in the zona
      glomerulosa of the adrenal gland. With regard to the hypothalamo-neurohypophyseal
      AVP system, ANF binding sites were localized to the median eminence and
      neurohypophysis, but not to the magnocellular nuclei. ANF receptors were also
      labelled in structures lacking a blood-brain barrier such as the subfornical
      organ and the choroid plexus.

PMID- 1388031
TI  - Stimulus-induced coordinate changes in mRNA abundance in single postsynaptic
      hippocampal CA1 neurons.
AB  - The molecular effects of use-dependent changes in synaptic transmission were
      studied in individual CA1 pyramidal neurons from rat hippocampal slices.
      Potentiation of excitatory postsynaptic currents was associated with coordinate
      changes in the relative abundance of several mRNAs 30 min to 3 hr after
      stimulation. There was a 300% increase in calcium/calmodulin-dependent protein
      kinase II mRNA levels concordant with a 50% decrease in protein kinase C beta 1
      isoform mRNA. A 2-fold increase in zif-268 mRNA was seen, while increases in c
      fos and c-jun mRNA levels were inconsistent, gamma-Aminobutyric acid A receptor
      beta 1 subunit mRNA levels increased 3-fold. Potentiation-induced changes were
      prevented by N-methyl-D-aspartate receptor blockade. Changes in mRNA abundance in
      individual cells, with synaptic and glial interactions intact, combine to produce
      a molecular fingerprint of a potentiated CA1 neuron.

PMID- 1388033
TI  - Isolation and characterization of a new acetate-requiring mutant strain, ace-9,
      of Neurospora crassa.
AB  - A new acetate-requiring mutant strain of Neurospora crassa, ace-9, has been
      isolated. The mutant gene was mapped between nuc-2 and arg-12 on the right arm of
      the second linkage group. The ace-9 mutant strain shows very weak activity of
      pyruvate dehydrogenase complex (PDHC). Three strains that show no activity of
      PDHC had already been found, i.e., ace-2, ace-3, and ace-4. Thus the ace-9 is the
      fourth gene that causes the deficiency in PDHC activity by a mutation. Deficiency
      of PDHC activity in ace-9 strain seems to be due to defective E1 component,
      because (1) the activity of E1 component enzyme is very weak in ace-9 mutant
      strain, and (2) normal PDHC activity was resumed when a preparation of ace-9 was
      mixed with E1-E2 fraction of wild type or with E1 component of wild type E. coli.
      Difference in thermostability of both E1 component enzyme and PDHC between ace-9
      and the wild type strains supports this conclusion.

PMID- 1388032
TI  - Variations in chloroplast proteins and nucleotide sequences of three chloroplast
      genes in Triticum and Aegilops.
AB  - Two alloplasmic wheat lines having the same common wheat nucleus but the
      cytoplasms of Aegilops crassa and Ae. columnaris together with the corresponding
      normal line (control) were used in the two-dimensional gel electrophoresis of
      soluble and thylakoid membrane proteins of the chloroplast. Three chloroplast
      polypeptides: the Rubisco large subunit, the beta subunit of ATP synthase, and an
      unidentified 31 kDa protein, differed in the common wheat and two Aegilops
      cytoplasms. Three chloroplast genes, atpB, atpE and trnM, that respectively
      encode the beta and epsilon subunits of ATP synthase and tRNA(met), were
      sequenced. The atpB gene differed by two synonymous base substitutions, whereas
      the other two genes were identical in the two Aegilops cytoplasms. From the
      predicted amino acid sequences, the beta subunits of the ATP synthase in the
      Aegilops cytoplasms were assumed to have three amino acid substitutions: Ala by
      Val, Asp- by Ala, and Gln by Lys+, in contrast to the cytoplasm of common wheat.
      This accounts for the difference in pI values found for the common wheat and
      Aegilops cytoplasms. The two base substitutions for the atpE genes of common
      wheat and the Aegilops cytoplasms were synonymous. The differences detected in
      the genes encoding the two subunits of ATP synthase do not appear to be
      ascribable to the differences in phenotypic effects for the common wheat and
      Aegilops cytoplasms. The base substitution rate of the atpB-atpE-trnM gene
      cluster was similar to that of the rbcL gene. From the rate for the atpB gene
      alone, evolutionary divergence of the wheat-Aegilops complex is assumed to have
      begun ca. 3.0 x 10(6) years ago, as compared to ca. 8.0 x 10(6) years ago for the
      divergence of the wheat-Aegilops complex and barley.

PMID- 1388034
TI  - Interaction of fibronectin and fibronectin binding protein (FnBP) of
      Staphylococcus aureus with murine phagocytes and lymphocytes.
AB  - In the present study we examined the in vitro and in vivo interactions of a
      cloned staphylococcal fibronectin binding protein (FnBP) and plasma fibronectin
      (Fn) with polymorphonuclear cells (PMNs) and macrophages, and how antibodies
      against FnBP affect the phagocytosis process in vitro. Moreover, the interaction
      of FnBP and Fn coupled on latex beads as 'artificial bacteria' and 'artificially
      opsonized bacteria' with murine spleen cells and peritoneal macrophages was
      tested. The major finding of the present study is that antibodies against the
      FnBP of Staphylococcus aureus (S. aureus) and low concentration of antibodies
      recognized two IgG-binding domains of protein A (SpA) are effective in the
      promotion of phagocytosis in vitro. It was also observed that FnBP has a
      chemoattractant activity and causes accumulation of PMNs and macrophages in the
      mouse peritoneal cavity when injected 24 h before irritation of peritoneal
      exudate. It seems likely that this activity is connected with binding to Fn
      molecules since formalin inactivation of FnBP (60%) abolished it. In the in vitro
      phagocytosis assay in the presence of FnBP (in a medium supplemented with serum
      depleted of Fn), ingestion of bacteria by phagocytes was identical to assay
      carried out in the presence of BSA. However, addition of plasma fibronectin
      caused an increased uptake of bacteria by macrophages and to a lesser degree by
      PMNs. We observed that in a population of normal splenocytes, those cells that
      effectively bound FnBP- and Fn-coated latex beads were mostly those cells
      exhibiting macrophage and dendritic morphology. In populations of spleen cells of
      animal infected with S. aureus, T lymphocytes were also found to bind FnBP- and
      Fn-coated latex beads. These data suggest that FnBP may have the ability to
      promote aggregation of immune cells, either directly or by interaction with
      plasma Fn, which can be helpful in certain cell-cell interactions taking place at
      the initial stages of specific immune response.

PMID- 1388035
TI  - Effect of D-myo-inositol on platelet function and composition and on cataract
      development in streptozotocin-induced diabetic rats.
AB  - Diabetes is known to be associated with an increase in aldose reductase activity,
      platelet hyperaggregability, lipid peroxidation, and cataract formation. A
      molecule, D-myo-inositol 1,2,6-trisphosphate (PP-56), derived from phytic acid,
      could in principle, by supplying myoinositol to tissues and acting as an
      antioxidant, counteract some of the manifestations of diabetes. Thus, the effects
      of PP-56 on platelet aggregation, fatty acids, and polyols were investigated in
      uncontrolled streptozotocin-induced diabetes in rat in relation to cataract and
      lipid peroxidation. A decrease in the response of platelet aggregation to
      thrombin and ADP (P less than 0.05, P less than 0.001) and in the level of
      sorbitol and the ratio sorbitol/myo-inositol (P less than 0.01) in platelets was
      observed in the rats treated by PP-56 for 7-8 weeks. These beneficial effects
      were associated with an incidence of cataract reduced by 26 to 44% (P less than
      0.05 to P less than 0.001) depending on the duration of treatment. They were also
      accompanied by a significant lower plasma level of malondialdehyde (P less than
      0.05), and, more markedly, of conjugated dienes (P less than 0.001) as well as an
      increase in platelet lipids of the 20:4(n-6)/20:3(n-6) ratio, an index of delta 5
      desaturase activity. PP-56 appears to modulate fatty acid desaturases and aldose
      reductase in platelets and delay by a few weeks the development of cataract in
      this acute model of diabetes.

PMID- 1388037
TI  - Goserelin depot in the treatment of premenopausal advanced breast cancer.
AB  - 333 pre- and peri-menopausal patients with breast cancer entered a programme of
      open studies on the effect of goserelin. Of the 333 patients, 265 patients were
      entered into assessable efficacy studies. Efficacy data were analysed from 228
      eligible patients receiving 3.6 mg of goserelin administered as a subcutaneous
      injection of a depot formulation once every 28 days. Mean serum luteinising
      hormone (LH) and oestradiol concentrations were suppressed by day 22 after the
      first injection. Subjective response occurred in 68.3% of patients assessed.
      Objective response (UICC criteria) occurred in 36.4% of patients and the
      lifetable median duration of response was 44 weeks. Responses were observed in
      all histological grades of tumour, and regardless of oestrogen receptor status.
      Treatment was well tolerated with no withdrawals due to possible adverse
      reactions of which hot flushes (75.9%) and loss of libido (47.4%) were commonly
      encountered. Goserelin provides an effective well tolerated medical alternative
      to ovarian ablation in the management of advanced breast cancer.

PMID- 1388036
TI  - Antitumour synergism between non-toxic dietary combinations of isotretinoin and
      glucarate.
AB  - Dietary calcium glucarate (CGT) increased the activity of non-toxic levels of
      dietary isotretinoin against pre-established tumors in the chemically-induced rat
      mammary tumour model. In the range of 1.0-1.5 mmol/kg diet, isotretinoin enhanced
      tumour growth by 20% over a 4 week course of treatment. Tumour growth inhibition
      not exceeding 15% was observed only at dosages as high as 2.0 mmol/kg, i.e. in
      the cumulative toxicity range. Growth inhibition by 64 mmol/kg diet of CGT alone
      was marginal, varying from zero to 8%. In contrast, the combination of 1.0
      mmol/kg of isotretinoin and 64 mmol/kg of CGT caused a reversible inhibition of
      tumour growth, culminating in a net decrease in tumour volume of 20%. This study
      documents the marginal enhancement of tumour growth by high sub-optimal
      concentrations of isotretinoin alone, and describes conditions for inhibition of
      tumour growth by sub-optimal concentrations of the natural retinoid. Related in
      vitro studies on retinoid sensitive and insensitive cell lines suggest that the
      anticancer activity of the combination is dependent on sensitivity of the cells
      to retinoids.

PMID- 1388038
TI  - Intravenous clodronate for the treatment of hypercalcaemia in breast cancer
      patients with bone metastases--a prospective randomised placebo-controlled
      multicentre study.
AB  - In a double blind randomised multicentre study the effect of intravenous
      clodronate plus hydration was compared with placebo plus hydration in the
      treatment of hypercalcaemia in breast cancer patients with bone metastases. The
      patients were treated either with hydration plus clodronate 300 mg/day or
      hydration plus placebo, up to 7 days or until serum ionised calcium was below 1.4
      mmol/l. 25 patients received clodronate and 19 placebo. A significant difference
      in favour of clodronate was observed in the time to reach normocalcaemia (P =
      0.004) and in the number of patients achieving normocalcaemia (P = 0.0003). 17
      patients of 21 evaluable patients on clodronate achieved normocalcaemia compared
      with 4 of 19 patients on placebo. The only adverse event clearly associated with
      clodronate was symptomatic hypocalcaemia in 1 patient. Thus, clodronate seems to
      be a safe and highly efficacious drug for the treatment of hypercalcaemia in
      breast cancer patients.

PMID- 1388039
TI  - [Analysis of growth, phenotype and cytotoxic activity of tumor infiltrating
      lymphocytes expanded in vitro with interleukin-2 and interleukin-4: preliminary
      results].
AB  - Tumor infiltrating lymphocytes (TIL) play an important role in the host immune
      response to cancer. When these cells are reinfused into cancer patients after in
      vitro expansion with lymphokines such as interleukin 2 (rIL-2), they often induce
      regression of tumor metastases. We obtained TIL of enzymatic digestion of 7 human
      solid tumors and then cultured them with rIL-2 and interleukin 4 (IL-4) at
      different concentrations for about 36 days. Immunophenotypic analysis was
      performed at the end of the second and fourth week; cytotoxic activity against
      autologous and heterologous targets was assessed on the 30th day of culture. The
      best lymphocytic growth was observed when we used rIL-2 and IL-4 for the first
      two weeks of culturing and then continued with rIL-2 alone. CD3 and CD56 cells
      formed the majority of TIL in all cultures. In 4 cases CD4 cells predominated at
      the initial stage of culturing, with CD8 cells gradually increasing and finally
      inverting the CD4/CD8 ratio. Autologous cytotoxicity (3/4 cases) appeared to be
      better in those patients in whom the CD4/CD8 ratio was inverted. These data
      enable identification of the combination of lymphokines that will will best
      provide expansion of live TIL active against tumoral cells. This procedure must
      be followed before in vivo reinfusion of expanded lymphocytes is carried out.

PMID- 1388040
TI  - In vivo and in vitro antitumor activity of mitomycin C conjugates at 7-N position
      through a linker containing thiocarbamate bond with CD10 monoclonal antibody.
AB  - Through a linker containing thiocarbomate bound to the 7-N position of mitomycin
      C (MMC), conjugates with a monoclonal antibody to CD10 (NL-1) were prepared, and
      their antitumor activities were examined. All five conjugates, except one, showed
      in vitro cytotoxicity to two CD10+ lymphoid cell lines superior to MMC. The
      conjugate displaying the highest cytotoxicity was selected and further tested
      against three CD10+ and two CD10- lymphoid cell lines in vitro. The conjugate
      with NL-1 antibody demonstrated higher cytotoxic activity against CD10+ tumor
      cells than the control conjugate with normal immunoglobulin, while there was no
      significant difference, when tested against CD10- tumors. The cytotoxic activity
      of the NL-1 conjugate to CD10+ tumors was significantly blocked by NL-1 antibody.
      In vivo antitumor activity of the NL-1 conjugate was then tested against a CD10+
      tumor transplanted to nude mice, and side effects were recorded. The NL-1
      conjugate (4 mg/kg) showed an in vivo antitumor effect similar to MMC (2 mg/kg),
      which is at nearly maximal tolerable dose; the latter induced decreases in
      numbers of leukocytes and platelets, while the former did not, suggesting less
      side effect by the NL-1 conjugate. Since MMC demonstrates a broad spectrum of
      antitumor activity, the conjugate, as such, may be applicable for the treatment
      of cancer patients.

PMID- 1388041
TI  - The role of cytochrome P4502D6 in the metabolism of paroxetine by human liver
      microsomes.
AB  - Paroxetine is a selective serotonin reuptake inhibitor possessing anti-depressant
      activity. Demethylenation of the methylenedioxy phenyl group is the initial step
      in its metabolism, the liberated carbon appearing in vitro as formate. A
      radioassay involving [14C-methylenedioxy] paroxetine was developed and used to
      examine the role of cytochrome P4502D6 in paroxetine metabolism by human liver
      microsomes. The rate of formate production was much higher in microsomes from an
      extensive metaboliser of debrisoquine than from a poor metaboliser. Also,
      demethylenation of paroxetine was inhibited by the quinidine and quinine isomer
      pair in microsomes from the extensive metaboliser only. These observations
      strongly suggested that the process was catalysed by the enzyme cytochrome
      P4502D6. Metabolism could not be completely inhibited by quinidine, the residual
      activity representing the contribution of at least one other enzyme. The ability
      of microsomes from a poor metaboliser of debrisoquine to demethylenate paroxetine
      provided further evidence for the involvement of an enzyme distinct from P4502D6.
      This was confirmed by kinetic analysis of the process in microsomes from both
      poor and extensive metabolisers. It is concluded that, in man, the initial step
      of paroxetine metabolism is performed by at least two enzymes, one of which is
      cytochrome P4502D6.

PMID- 1388042
TI  - Mammographic screening: efficacy and guidelines.
AB  - Over the past year, concerns regarding breast cancer screening guidelines and the
      benefits of mammography have been raised. These concerns were fueled by a leak of
      information from the Canadian National Breast Screening study that suggested
      first an increase in mortality in women aged 40 to 49 years and then, after
      further investigation, no change in mortality for women screened with mammography
      as compared with those who relied on physical examination. No benefit from the
      addition of mammography to physical examination was reported for women aged 50 to
      59 years. Published data demonstrate poor mammographic images in the first 3
      years of the study. Direct evidence of benefit in women aged 40 to 49 years is
      available only in the Health Insurance Plan trial in which two-view mammography
      plus physical examination resulted in a delayed reduction in mortality equal to
      that in older women. The other trials, except for the Canadian trial, used less
      sensitive protocols and frequently used single-view mammography at 2- or 3-year
      intervals. Evidence from the Breast Cancer Detection Demonstration Project
      suggested benefit in screening women aged 40 years or older with annual
      mammography and physical examination. This paper reviews 11-year results from the
      Swedish two-county study and the results of other studies and discusses factors
      related to frequency, sensitivity, and lead-time.

PMID- 1388043
TI  - Leukemia in Down syndrome: a review.
AB  - The incidence of leukemia is higher in children with Down syndrome (DS) than in
      normals. In approximately 50% of cases the type of leukemia is acute
      megakaryoblastic leukemia (AMKL) and it occurs during the first 4 years of life.
      The leukemic cell also has features of erythroid progenitors and therefore
      appears to be a precursor cell with biphenotypic properties. In addition,
      newborns with DS frequently develop transient leukemia (TL), which is
      characterized by the presence of megakaryoblasts in the blood which disappear
      during the first 1-3 months of life. The incidence of this disorder is unknown
      although preliminary studies suggest that megakaryoblasts may be found frequently
      in the blood of DS newborns. TL does not occur in normal newborn infants.
      Although TL disappears spontaneously, many of these children will develop AMKL at
      1-4 years of age. Recent surveys suggest that 20-30% of newborns with TL will
      develop AMKL. Preliminary evidence suggests that TL is a clonal proliferation,
      can be fatal, and may occur in a specific subgroup of DS children. The
      observations in this report are drawn from our own experience, reports in the
      literature, and data accumulated in the Canadian Down Syndrome Leukemia Registry.

PMID- 1388044
TI  - Idiopathic hypereosinophilic syndrome terminating in acute lymphoblastic
      leukemia.
AB  - Idiopathic hypereosinophilic syndrome (IHES) is a heterogeneous group of
      disorders characterized by multisystem dysfunction and persistent, extreme
      eosinophilia of unknown cause. We describe a 9-1/2-year-old boy whose course
      included several unusual clinical features and terminated 2 years after diagnosis
      in acute lymphoblastic leukemia (ALL). Serial studies suggest that leukemia was
      not present earlier in his course. We speculate that this child may have had an
      evolving lymphoproliferative syndrome with a terminal blast crisis to which the
      eosinophilia was a nonmalignant leukemoid reaction.

PMID- 1388045
TI  - Role of 5 alpha-reduction in progesterone's ability to release FSH in estrogen
      primed ovariectomized rats.
AB  - In ovariectomized estrogen-primed rats, progesterone as well as 5 alpha
      dihydroprogesterone (5 alpha-DHP) are capable of inducing the release of
      gonadotropins. This study examined the need of 5 alpha-reduction as a
      prerequisite for the action of progesterone. The 5 alpha-reductase inhibitor, N,N
      diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carboxamide was injected
      at a 1 or 2 mg dose/rat 2 h prior to an injection of 0.4 or 0.8 mg
      progesterone/kg body weight at 0900 h to immature ovariectomized, estrogen-primed
      rats and serum was analyzed for LH and FSH at 1500 h. Pituitary and hypothalamic
      5 alpha-reductase activity was measured at the time of progesterone
      administration and at the time of the surge by incubating tissue homogenates with
      [3H]progesterone. Substrate, ([3H]progesterone) and product ([3H]5 alpha-DHP),
      were separated by reverse phase HPLC. The pituitary 5 alpha-reductase activity
      was not blocked at 1500 h. However, both pituitary and hypothalamic 5 alpha
      reductase was blocked at the time of progesterone administration. No effect was
      seen by acute administration of the 5 alpha-reductase inhibitor upon either the
      0.4 or 0.8 mg progesterone/kg-induced release of LH and FSH. There was, however,
      a specific, significant inhibition of progesterone-induced FSH but not LH release
      when the 5 alpha-reductase inhibition was sustained throughout the afternoon of
      the gonadotropin surge. These results indicate a biologically significant role
      for the irreversible 5 alpha-reduction of progesterone in the modulation of the
      release of FSH.

PMID- 1388046
TI  - Kinetic evidence for separate 3 beta-hydroxysteroid dehydrogenase-isomerases in
      androgen and 16-androstene biosynthetic pathways in the pig testis.
AB  - The microsomal fraction from the testes of immature pigs (less than 1 week old)
      contains 3 beta-hydroxysteroid dehydrogenase-isomerase (3 beta-HSD-isomerase)
      activities that convert dehydroepiandrosterone (DHA) to 4-androstenedione and
      5,16-androstadien-3 beta-ol (andien-beta) to 4,16-androstadien-3-one (dienone).
      These reactions are necessary for the biosynthesis of hormonally and pheromonally
      active steroids. Kinetic analyses of these activities were done to determine
      whether they are catalysed by a single enzyme or if there is any interaction
      between the substrates and products of one reaction on the activity of the other
      enzyme. Kinetic parameters were determined and the affinities for steroid
      substrate were similar (7-9 mumol/l) but the Vmaxapp value for the conversion of
      andien-beta to dienone was 10-fold that of the DHA to 4-androstenedione reaction.
      In analyses of the conversion of DHA to 4-androstenedione, neither andien-beta
      nor dienone inhibited the reaction and especially, no effect on the Kmapp for DHA
      was observed which would have indicated competition between DHA and andien-beta
      for the same active site (Kiapp from slope and intercept replots were between 3
      and 80 times the values of the kinetic constants). Similarly, DHA and 4
      androstenedione had minor or negligible effects on the conversion of andien-beta
      to dienone (Kiapp from slope replots were the same as the Kmapp but the Kiapp
      from the intercept replot was 12 to 25% of the Vmaxapp). It is concluded that
      substrate specific 3 beta-HSD-isomerases for andien-beta and DHA exist in the
      immature pig testis and there is little, if any interaction between these
      enzymes.

PMID- 1388047
TI  - Aromatization inhibition alone or in combination with GnRH agonists for the
      treatment of premenopausal breast cancer patients.
AB  - Aromatase inhibition in postmenopausal women causes a marked fall in the plasma
      levels of oestrogens and is an effective treatment for breast cancer, however,
      trials with aminoglutethimide found that this aromatase inhibitor was ineffective
      in suppressing plasma oestrogen levels in premenopausal breast cancer patients.
      We found that the more potent inhibitor, 4-hydroxyandrostenedione (4-OHA), which
      can suppress oestrogen synthesis in rodents and non-human primates with intact
      ovarian function, was also unsuccessful as an oestrogen suppressant in
      premenopausal women at its maximum tolerated dose (500 mg/week i.m.). GnRH
      agonists are effective suppressants of ovarian oestrogen synthesis but oestrogen
      production from peripheral sites is unaffected. Our studies of a combination of
      the GnRH agonist goserelin and 4-OHA demonstrated that the combination caused
      greater oestrogen suppression than goserelin alone and led to objective clinical
      response in 4/6 breast cancer patients after their relapse from treatment with
      goserelin as a single agent. The combination of a GnRH agonist and an aromatase
      inhibitor should be subjected to clinical trials.

PMID- 1388048
TI  - Fadrozole hydrochloride, a new nontoxic aromatase inhibitor for the treatment of
      patients with metastatic breast cancer.
AB  - Eighty previously treated postmenopausal women with metastatic breast cancer were
      randomized to receive fadrozole (CGS 16 949A), a new aromatase inhibitor, 1 or 4
      mg orally per day. Seventy eight patients were evaluable for toxicity and
      response. Only mild to moderate toxicity, namely hot flushes (28%), nausea and
      vomiting (13%), fatigue (8%) and loss of appetite (5%) occurred. Complete
      response was documented in 10% and partial response in 13% of patients with 45%
      having a no change status for at least 2 months. The median time to treatment
      failure is 4.1 months. The median survival is 23.7 months. The median survival is
      23.7 months. The response and survival in patients with estrogen receptor
      positive and estrogen receptor unknown disease were not significantly different.
      Neither response nor survival was significantly different between the patients
      receiving 1 or 4 mg of fadrozole per day. Fadrozole is a well tolerated,
      effective second line treatment for women with metastatic breast cancer.

PMID- 1388049
TI  - Tissue androgens and the endocrine autonomy of breast cancer.
AB  - To evaluate whether a tumour-directed gradient in androgen levels in fatty tissue
      can account for the maintenance of intra-tissue oestradiol levels,
      androstenedione (Adione), dehydroepiandrosterone (DHEA), testosterone (Testo) and
      androstenediol (Adiol) were assayed in breast tumour tissues and in fatty tissue
      taken at different distances from the tumour. The concentration of Adione was
      significantly lower in tumour tissue (5.6 +/- 1.5 pmol/g tissue; mean +/- SEM; n
      = 14) than in the adjacent fatty tissue (20.4 +/- 2.2; P less than 0.005). Testo,
      by contrast, occurred in equal concentrations in tumour (0.80 +/- 0.11) and in
      adjacent fatty tissue (0.70 +/- 0.07). Adione levels tended to be lower after the
      menopause only in fatty tissue, not in the tumour tissue; for Testo no
      differences were observed between samples from pre- and postmenopausal patients.
      Tumour DHEA levels (57 +/- 12 pmol/g tissue) were lower than those in fatty
      tissue (117 +/- 17; P less than 0.02). As with Adione, fatty tissue DHEA
      concentrations tended to be higher in pre- than in postmenopausal patients. Adiol
      showed a similar pattern as Testo. For none of the aromatase substrates nor their
      precursors a tumour-directed gradient was observed. The concentration of Adione
      in breast cancer tissue is much lower than the reported Km of the aromatase
      system for Adione. We have concluded, therefore, that the maintenance of
      oestradiol concentrations in tumour tissues is not substrate-driven.

PMID- 1388050
TI  - The Wnt gene family in tumorigenesis and in normal development.
AB  - Various members of the Wnt gene family have been identified as activated
      oncogenes in mouse mammary tumors. We show that some tumors are oligoclonal for
      activation of a Wnt gene, and clonal variation when those tumors are transplanted
      to become hormone-independent. The normal function of many Wnt genes is to
      control pattern formation in early embryos, as shown by expression profiles and
      by mutant analysis.

PMID- 1388051
TI  - The Myo as an oral prophylactic device used by motor skill functionally disabled
      patients.
AB  - The Myo appliance appears to be effective in reducing plaque and gingival
      inflammation. The advantage of this appliance is that the filament-like
      projections remove the plaque when the patient chews on the appliance. The use of
      the appliance is simple, does not require training or manual dexterity and is
      well accepted by the children.

PMID- 1388052
TI  - Trends in dental treatment rendered under general anesthesia, 1978 to 1990.
AB  - While it is generally accepted that the prevalence of dental caries is
      decreasing, many institutions report an increase in the demand for dental
      rehabilitation under general anesthesia. This paper compares the characteristics
      of patients and types of dental treatment delivered under general anesthesia at
      the same hospital during 1978-1980 and 1988-1990. Patient records for children,
      who received dental care under general anesthesia during the two time periods
      examined were reviewed. Demographic data as well as data pertaining to types of
      dental treatment performed were collected from each patient record. Demographic
      characteristics were analyzed with a chi square analysis, and results regarding
      the types of dental treatment were analyzed using a Students t-test. Results were
      considered significant at p less than 0.05. There were no statistically
      significant differences in gender or ethnicity of the patients treated during
      1978-1980 compared to 1988-1990. There were statistically significantly more
      patients treated in the 4-6 age group during 1988-1990 than during 1978-1980.
      There were no statistically significant differences in the number of dental
      procedures completed per patient during 1978-1980 compared to 1988-1990 in any
      procedure category except for dental sealants. This study indicates that the
      majority of pediatric dental patients being treated under general anesthesia at
      this hospital facility, still require an extensive amount of restorative dental
      care. Although most children can be successfully treated in the dental office,
      there is a group of pediatric patients, who require dental treatment in the
      hospital, under general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388053
TI  - Preventive dental health practices of non-institutionalized Down syndrome
      children: a controlled study.
AB  - Although Down syndrome children are known to be greatly predisposed to
      periodontal disease when compared with normal children, the preventive dental
      health practices of non-institutionalized Down syndrome children have not been
      well reported. This questionnaire study of 25 Down syndrome children aged 1-14
      years compared with 25 normal control children showed that Down syndrome children
      have poorer dental health practices compared with normal children. Significantly
      greater numbers of Down syndrome children were weaned from the bottle at greater
      than 18 months of age (56% vs 24%, p less than 0.05) or had taken a bottle to bed
      (40% vs 12%, p less than 0.05), indicating their increased risk for the
      development of nursing bottle caries. In addition, Down syndrome children were
      receiving less help during tooth brushing (60% vs 84%, p less than 0.05), were
      older when they first visited the dentist, and less likely to be taking regular
      fluoride supplements. These results indicate that Down syndrome children are
      further disadvantaged by poor preventive dental health practices and should be
      targeted for increased preventive dental care.

PMID- 1388054
TI  - The office logo and practice brochure: two necessary marketing tools for the
      pediatric dentist.

PMID- 1388055
TI  - Biosynthesis of marsupial milk oligosaccharides. II: Characterization of a beta 6
      N-acetylglucosaminyltransferase in lactating mammary glands of the tammar
      wallaby, Macropus eugenii.
AB  - Tammar wallaby (Macropus eugenii) mammary glands contain a UDP-GlcNAc:Gal beta 1-
      --3Gal beta 1----4Glc beta 1----6-N-acetylglucosaminyltransferase (GlcNAcT) whose
      activity has been characterized with respect to the effect of pH, apparent Km for
      acceptor, effects of bivalent metal ions, acceptor specificity and identity of
      products. The enzyme did not show an absolute requirement for any bivalent metal
      ion but its activity was increased markedly by Mg2+, Ca2+ and Ba2+ and, to a
      lesser extent, by Mn2+. When Gal beta 1----3Gal beta 1----4Glc was used as
      acceptor, the product was Gal beta 1----3[GlcNAc beta 1----6]Gal beta 1----4Glc.
      With Gal beta 1----3Gal beta 1----3Gal beta 1----4Glc as acceptor, the product
      was shown, by 1H-NMR spectroscopy and exo-beta-galactosidase digestion, to be a
      novel pentasaccharide with the structure Gal beta 1----3[GlcNAc beta 1----6]Gal
      beta 1----3Gal beta 1----4Glc, suggesting that the enzyme recognises the non
      reducing end of the acceptor substrate, rather than the reducing end.

PMID- 1388056
TI  - [Metabolic and functional consequences of complete inhibition of creatine kinase
      by iodoacetamide in the perfused heart].
AB  - Treatment of perfused rat hearts with 0.5 mM iodoacetamide (IAAm) for 15 min at
      different workloads resulting in a nearly complete inhibition of creatine kinase
      (CK, 99%) was followed by a rapid decline of the phosphocreatine (PCr) level
      (30%) and a 2-fold increase of the P(i) level which then stabilized. Conversely,
      the ATP content started to drop monotonously at the beginning of the IAAm washout
      and reached 30% 90 min after the IAAm removal under medium load. Under low
      workload the ATP decay occurred at later periods. Neither the ADP-stimulated
      mitochondrial respiration in skinned fibers, nor the Ca(2+)-stimulated ATPase
      activity of myofibrils was affected by IAAm treatment. The sensitivity of the
      resting tension of skinned fibers to Ca2+ tended to a slight increase. The
      cardiac work index (PRP-pressure-rate product) decreased by 25%, while the end
      diastolic pressure (EDP) rose by 15 mm Hg when IAAm acted under medium load. In
      contrast, under low work these parameters were practically stable. The hearts
      poisoned with IAAm performed a two times lower maximal work and had reduced (by
      35%) oxygen consumption rates. The efficiency of energy utilization for
      mechanical work decreased by 40%. The changes in PRP and EDP correlated with the
      cytosolic [ATP]/[ADP] ratio in such a way that the decrease in the latter was
      associated with a decrease in PRP and the elevation of EDP. These data suggest
      that the creatine kinase system is necessary for the effective translation of a
      high [ATP]/[ADP] ratio from the intermembrane space of mitochondria to the
      cytoplasm, myofibrils and ionic pumps. This provides a high level of mechanical
      work and good relaxation of the left ventricle and protects cytosolic adenine
      nucleotides from the breakdown.

PMID- 1388057
TI  - Three types of naturally occurring modified lipoproteins induce intracellular
      lipid accumulation in human aortic intimal cells--the role of lipoprotein
      aggregation.
AB  - Blood monocytes or intimal smooth muscle cells from normal aorta were incubated
      with low density lipoprotein (LDL) from patients with coronary atherosclerosis,
      or with LDL from diabetic patients, or with lipoprotein(a) (Lp(a)). In each case
      there was a 2- to 4-fold rise in the intracellular cholesteryl ester content. LDL
      from healthy subjects failed to induce intracellular lipid accumulation in these
      cells. LDL from patients with coronary atherosclerosis, LDL from diabetic
      patients, and Lp(a) form aggregates under cell culture conditions. The ability of
      these lipoproteins to increase the cholesteryl ester content of cultured cells is
      directly correlated to the degree of lipoprotein aggregation. When aggregates
      were removed from the lipoprotein preparations by filtration, the latter became
      less effective in promoting intracellular lipid accumulation. Incubation of cells
      with lipoprotein aggregates, isolated by gel filtration, induced a 3- to 5-fold
      elevation of the cellular cholesteryl ester content. These results suggest that
      LDL from atherosclerotic patients, or LDL from diabetic patients, or Lp(a) have a
      tendency to form aggregates and that these aggregates are avidly taken up by
      intimal smooth muscle cells followed by lipid accumulation. This aggregation
      tendency may play a role in atherogenesis.

PMID- 1388058
TI  - Bioluminescence enhanced enzyme immunoassay for human alpha-atrial natriuretic
      peptide using luciferin-luciferase.
AB  - A sensitive bioluminescent enzyme immunoassay (BEIA) for the determination of
      human alpha-atrial natriuretic peptide was developed. The usable ranges of the
      standard curve extend from 10 pg to 400 pg for the one-step method and from 2.5
      to 50 pg for the two-step method.

PMID- 1388059
TI  - Extracorporeal membrane oxygenation in lambs through umbilical vessel perfusion:
      cardiac and hepatic complications.
AB  - Twin lambs were delivered by ceasarean section near term, aralyzed, sedated and
      randomly assigned to either mechanical ventilation or umbilical arteriovenous
      ECMO for 48 hours. Umbilical arteriovenous ECMO provided adequate gas exchange
      with minimal or no ventilation of the native lungs. However, at autopsy, animals
      treated with umbilical ECMO showed right heart dilation and liver necrosis or
      hemorrhage compared to their twins treated with mechanical ventilation.

PMID- 1388060
TI  - Calcium channel blockade interacts with a neuroleptic to attenuate the
      conditioning of amphetamine's behavioral effects in the rat.
AB  - Conditioned responses to drug-related cues appear to be related to the
      maintenance of stimulant addiction. These conditioned responses are not blocked
      by treatments that block the direct effects of stimulants and may contribute to
      the high rate of relapse of addicts. Rats administered (+)-amphetamine in a
      specific environment exhibit conditioned locomotion when subsequently placed in
      that environment without drugs. The neuroleptic haloperidol significantly
      attenuated amphetamine-induced locomotor activity but failed to reduce
      conditioned locomotion. Nimodipine, an L-type calcium channel antagonist, had no
      effect on amphetamine-induced unconditioned or conditioned locomotion. However,
      combined nimodipine and haloperidol treatment blocked the unconditioned and
      attenuated the conditioned locomotor response to amphetamine. Conjunctive therapy
      with nimodipine and haloperidol may provide an efficacious treatment for
      stimulant addiction. In addition, nimodipine may provide an important adjunctive
      therapy for schizophrenia, allowing the use of lower doses of neuroleptic to
      avoid extrapyramidal side effects.

PMID- 1388061
TI  - Cyclosporin A is a hormonal immunomodulator. I. Human study.
AB  - The immunosuppressant Cyclosporin A (CS) is known to induce 2 hormonal disorders
      as side effects of its long-term use: gynecomastia in male subjects and hirsutism
      in female subjects. The present study was started to investigate the problem of
      whether or not the above steroid-mimetic actions of CS are to be related to the
      immunosuppressive effect of that substance. Practically, a case-control
      comparison of 14 urinary steroid excretions was made for each sex with healthy
      controls and kidney transplant recipients undergoing CS-free and CS-dependent
      immunosuppressive treatments on the one hand, and the success rate of kidney
      transplantation was compared between the CS-free treatment group and the CS
      dependent treatment group on the other hand. The results obtained are follows: 1)
      Both the CS-free- and CS-dependent-treatments produced a general depression of
      all androgens, progestins and corticosteroids in the urine. The suppressive
      effect on urinary steroid excretions was more marked in the latter than in the
      former. Under the same CS-free treatment, the excretion of tetrahydrocortisol
      (THF) was intact in male patients and was significantly depressed in female
      patients. 2) A remarkable difference between the 2 immunosuppressive treatment
      groups was found in the ratio of urinary androsterone (AD) to urinary THF, an
      index of androgen to glucocorticoid balance: the praxis of CS-free treatment
      significantly depressed log AD/THF in patients of both sexes, the ratio being
      much higher in normal males than in normal females.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1388062
TI  - Effect of luteinizing hormone-releasing hormone analogs containing cytotoxic
      radicals on growth of estrogen-independent MXT mouse mammary carcinoma in vivo.
AB  - Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist
      [D-Lys6]LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys6]LH-RH coupled to
      glutaryl-2-(hydroxymethyl)anthraquinone) (G-HMAQ) and T-121/B (antagonist
      containing two residues of G-HMAQ) were tested in female BDF1 mice bearing MXT
      ((3.2)/Ovex) estrogen-independent mammary tumors. All three cytotoxic LH-RH
      analogs, administered from Alzet Osmotic Minipumps for 3 weeks, produced a
      significant inhibition of tumor growth. The effects of T-98 and T-121/B were
      superior to those obtained by treatment with equimolar doses of cytotoxic moiety
      anthraquinone or the LH-RH carrier alone. We assume that cytotoxic LH-RH analogs
      have a combined hormonal and cytotoxic activity with a reduced toxicity after
      administration in vivo. This is the first demonstration of in vivo tumor
      inhibition by targeted LH-RH analogs bearing cytotoxic radicals.

PMID- 1388064
TI  - Laparoscopic inguinal herniorrhaphy: classification and 1 year experience.
AB  - The laparoscopic transabdominal preperitoneal repair of inguinal hernias was
      utilized in 125 patients in a 12 month period. One hundred and forty three
      hernias were repaired. These hernias were classified into five different types
      depending on the site and size of the defect and whether they were primary or
      recurrent. Cylindrical plugs and screen were used in the first 37 repairs with 2
      recurrences and Mushroom Plugs and screen were used in 106 repairs with no
      recurrences. The two recurrences occurring with the cylindrical plugs were in
      indirect inguinal hernias with dilated internal rings greater than 2 cm.

PMID- 1388063
TI  - Subjective and metabolic effects of clodronate in patients with advanced breast
      cancer and symptomatic bone metastases.
AB  - Twenty postmenopausal women (aged between 46 and 67 years old) with skeletal
      metastases from breast carcinoma were treated with clodronate 450 mg i.v. daily
      for 5 days and thereafter with 100 mg i.m. daily for 10 days. All patients
      received standard hormonal therapy (tamoxifen). Symptomatic pain (evaluated
      according to a linear analog scale), performance status (according to Karnofsky),
      serum alkaline phosphatase, serum creatinine and osteocalcin were measured before
      and after treatment on days 5, 15, 30 and 45. Scanning by radiology were
      performed pre- and post-therapy. Bone pain was significantly reduced in 15 out of
      20 patients. After clodronate treatment the base line value of circulating
      osteocalcin (3.2 +/- 1.6 ng/ml) showed a significant increase on days 30 and 45
      (p less than 0.001). Radiological assessment of bone lesions showed stable
      disease in 18 patients and progression in two patients. No adverse side effects
      were observed. These data show that clodronate provided pain relief in 75% of
      treated patients and the increase in circulating osteocalcin levels can be
      considered a marker of the stabilization of skeletal metastatic lesions.

PMID- 1388065
TI  - Cost effectiveness of laparoscopic cholecystectomy.
AB  - An investigation was undertaken to determine whether hospital charges for
      laparoscopic cholecystectomy are higher than those for traditional open
      cholecystectomy. Thirty consecutive cases of successfully completed laparoscopic
      procedures in a single surgeon's experience were compared to 30 open cases
      performed within the previous calendar year. Patients undergoing open
      cholecystectomy were excluded if coexisting medical problems or complications
      prolonged hospitalization beyond 7 days. Mean patient age was comparable (open
      cholecystectomy = 47.3 +/- 2.9, laparoscopic cholecystectomy = 46.5 +/- 2.7
      years), as was the incidence of other significant medical problems. Average
      duration of hospitalization was significantly longer for open cholecystectomy
      (3.6 = 0.2 days) than for laparoscopic cholecystectomy (1.0 +/- days, p less than
      .001). Average hospital charges for open cholecystectomy were $5606 +/- 496 and
      for laparoscopic cholecystectomy $4726 +/- 98. Hospital charges from operating
      room and recovery room charges alone were $2684 +/- 131 for laparoscopic
      cholecystectomy and $2196 +/- 113 for open cholecystectomy. These operating room
      charges represent a significantly higher percentage of total hospital charges for
      laparoscopic cholecystectomy than open cholecystectomy patients (laparoscopic
      cholecystectomy = 56.3 +/- 1.9%, open cholecystectomy = 41.2 +/- 1.5%, p less
      than .05). Average time for return to work or normal activity was significantly
      shorter for laparoscopic cholecystectomy 8.6 +/- 9 days) than for open
      cholecystectomy (32.4 +/- 3.6 days, p less than .001). The authors conclude that
      laparoscopic cholecystectomy is a cost effective procedure for the treatment of
      symptomatic cholelithiasis, and that increased operative costs more than offset
      the significantly decreased length of hospitalization.

PMID- 1388066
TI  - Initial experience with laparoscopic surgery: establishing a new surgical
      procedure.
AB  - Laparoscopic surgery impacted the surgical world in the United States in 1990.
      This report reviews the initial experience of 34 surgeons in 8 teaching hospitals
      of the Northeastern Ohio Universities College of Medicine. There were 538 cases
      reported from May 1, 1990 to January 31, 1991. There was no mortality and the
      morbidity rate was 4.8%, including three bile duct injuries. The conversion rate
      to an open procedure was 6.1%. The criteria for credentialing, training, and
      resident and faculty education are included. The data reported by the Surgery
      Department of Northeastern Ohio Universities College of Medicine are very similar
      to reported series from the current literature.

PMID- 1388067
TI  - Laparoscopic surgery in the treatment of Mirizzi's syndrome.
AB  - Mirizzi's syndrome is an unusual complication of cholelithiasis which results
      when an impacted cystic duct stone causes edema and compression of the adjacent
      common hepatic duct. The authors report the successful treatment of a patient
      with this syndrome by laparoscopic means. A flexible 5.0 mm choledochoscope was
      inserted under laparoscopic guidance into the dilated proximal cystic duct and
      the impacted stone was extracted. Though still a technically demanding procedure,
      the authors feel that under certain conditions, laparoscopic surgery may
      represent the preferred initial approach to patients with Mirizzi's syndrome.

PMID- 1388069
TI  - Laparoscopically-assisted hysterectomy for the management of a borderline ovarian
      tumor: a case report.
AB  - Borderline ovarian tumors account for 4% of ovarian neoplasms, an incidence which
      remains constant despite advancing age. Management for younger women can be
      unilateral oophorectomy, although simple hysterectomy with bilateral salpingo
      oophorectomy is more appropriate for women beyond childbearing age. The authors
      report a laparoscopic approach to a case of borderline ovarian tumor.

PMID- 1388068
TI  - Incidental appendectomy during laparoscopic cholecystectomy.
AB  - An operative experience of three patients who underwent incidental laparoscopic
      appendectomy during laparoscopic cholecystectomy is presented. The technique and
      indications are discussed. The authors conclude that incidental laparoscopic
      appendectomy is possible and safe with existing incisions performed in
      gallbladder surgery. However, well-controlled prospective studies should be
      performed prior to wide application of this technique.

PMID- 1388070
TI  - Laparoscopic cholecystectomy in situs inversus totalis.
AB  - A 51-year-old woman with known dextrocardia presented with left-sided abdominal
      pain and symptoms consistent with biliary colic and cholelithiasis. Abdominal
      ultrasound confirmed the diagnosis of gallstones, as well as situs inversus with
      the liver and gallbladder on the left side and the spleen on the right.
      Laparoscopic cholecystectomy was performed without incident. The procedure was
      uncomplicated except for being the mirror image of that done with the gallbladder
      in the normal location. Cholelithiasis occurring with situs inversus is rare and
      may present a diagnostic problem. The extrahepatic anatomy of the biliary and
      venous system is the mirror image of the right sided liver. Historic and genetic
      aspects of situs inversus, as well as current theories regarding its etiology are
      presented. Situs inversus totalis does not appear to be a contraindication to
      laparoscopic treatment of cholelithiasis.

PMID- 1388071
TI  - An unusual complication of laparoscopic cholecystectomy.
AB  - Thus far, the morbidity and mortality of laparoscopic cholecystectomy compares
      favorably to that of open cholecystectomy. Neither procedure, however, is without
      complications. Laparoscopic cholecystectomy combines diagnostic laparoscopy as
      well as cholecystectomy. It is the purpose of this article to briefly review
      these procedures and report an interesting variation: penetration of small bowel
      as a result of an unusual variation of a Meckel's Diverticulum.

PMID- 1388072
TI  - Percutaneous gastrostomy made simple.
AB  - The use of percutaneous endoscopic gastrostomy has obviated the necessity of
      laparotomy for enteral access. The authors propose a new technique for
      introduction of the gastrostomy tube. It entails use of the laparoscopic trocar
      to gain entrance into the gastric lumen.

PMID- 1388074
TI  - A simple, safe technique for placement of the veress needle and trocar in
      laparoscopy.
AB  - A simple technique of placing two Kocher clamps on the anterior rectus fascia for
      the elevation of the anterior abdominal wall during the insertion of the veress
      needle and the laparoscopic trocar is described in 243 consecutive patients.
      There were no failed insufflations during this study and no cases of
      preperitoneal emphysema. The technique is simple to use and adds safety to a
      basically blind procedure.

PMID- 1388073
TI  - Laparoscopic preperitoneal prosthetic inguinal herniorrhaphy.
AB  - Laparoscopic minimally invasive surgical procedures are gaining popularity and
      becoming more readily available. Presented here is an application of laparoscopy
      for the repair of groin hernias. Included are actual intraoperative photographs
      and descriptions of the technique with its rationale for the laparoscopic
      preperitoneal approach and the use of a prosthetic material.

PMID- 1388075
TI  - Placement of drains in laparoscopic procedures.
AB  - The technique of laparoscopic cholecystectomy is, in many areas, replacing the
      standard open cholecystectomy as the method of choice. Many surgeons are
      accustomed to the use of peritoneal drainage following cholecystectomy. The
      authors have developed a simple, effective, and rapid, yet controlled method of
      placing drains into the abdominal cavity, using laparoscopic techniques.

PMID- 1388077
TI  - Prevalence of overweight and obesity in Down's syndrome and other mentally
      handicapped adults living in the community.
AB  - To find out the prevalence of overweight and obesity in the mentally handicapped,
      183 subjects living in the community were studied; 58 of whom had Down's
      syndrome. It was found that 70.58% of males and 95.83% of females with Down's
      syndrome, and 49.29% males and 62.96% females from other mentally handicapped
      subjects, were categorized as overweight and obese, compared with 40% of males
      and 32% females in that category from normal population.

PMID- 1388076
TI  - The relationship between attitude to disabled siblings and ratings of behavioural
      competency.
AB  - The impact of maturation factors and functioning level on the relationship
      between disabled and non-disabled siblings was examined. Two groups of adults,
      distinguished by level of functioning of their mentally retarded sibling,
      completed a Schaefer Sibling Behavior Inventory (SBI) and participated in a semi
      structured interview. The latter explored a number of dimensions of the
      relationship including degree of warmth, contact and involvement. Judgements
      about involvement and comfort as remembered from the past and judgements about
      the present were obtained to derive hypotheses about possible changes with time.
      Data from the SBI indicated that significantly more competent siblings tended to
      be involved in relationships with a higher degree of reciprocity. In contrast,
      measures of attitude derived from interview data did not appear to relate to the
      functioning level of the sibling in any systematic manner. The results suggest
      that level of discomfort with peers may decrease significantly over the years
      with neither level of functioning nor gender being important variables. The
      extent to which non-disabled individuals expressed a preparedness to participate
      in the life of their disabled sibling may relate to the life-stage of the two.
      Males in particular anticipated increased future involvement. Although higher
      functioning siblings were described as more active in the relationship, this did
      not appear to influence perceived positiveness of regard. The implications of
      these results are discussed briefly.

PMID- 1388078
TI  - Lipids and lipoproteins in persons with Down's syndrome.
AB  - This study was designed to investigate whether the observed decreased prevalence
      of coronary artery disease in individuals with Down's syndrome may be explained
      by their serum lipid and lipoprotein profiles. Twenty-seven persons with Down's
      syndrome and 23 non-affected control individuals were enrolled in this study.
      Their fasting venous blood was analysed for total cholesterol, triglyceride, LDH
      cholesterol, HDL cholesterol, apo B and apo AI. The results revealed no
      significant differences between the study and control group with regard to total
      cholesterol, LDL cholesterol, apo B and the apo B:apo AI ratio. However,
      triglyceride levels were significantly increased, and serum HDL cholesterol, apo
      AI and HDL cholesterol:total cholesterol ratio were significantly decreased in
      patients with Down's syndrome when compared with the control group. The latter
      observations are all associated with an increased risk for coronary artery
      disease. Therefore, it is concluded that the decreased prevalence of coronary
      artery disease in individuals with Down's syndrome cannot be explained by the
      lipid and lipoprotein levels observed in this study population.

PMID- 1388079
TI  - Structure and function of actin.

PMID- 1388080
TI  - The role of Wnt genes in vertebrate development.
AB  - Over the past decade, many potential candidates for molecules involved in pattern
      formation in the vertebrate embryo have been identified. Manipulation of the
      expression of some of these factors has generated fascinating results that have
      allowed investigators to address their roles in embryogenesis. One such family
      consists of a group of putative cell signaling molecules related to the proto
      oncogene Wnt-1. An accumulating body of evidence suggests that the Wnt-family
      plays a major role in several aspects of vertebrate development.

PMID- 1388081
TI  - NMDA receptors in sensory information processing.
AB  - During the past year electrophysiological studies, particularly in the visual and
      somatosensory systems, have begun to uncover the specific roles played by NMDA
      receptors in the processing of sensory information. Many of the features of NMDA
      receptor-mediated sensory responses reflect known properties of the receptor.

PMID- 1388083
TI  - Whiplash injuries.

PMID- 1388082
TI  - Chemotherapy-induced acral erythema and acute graft-versus-host disease after
      allogeneic bone marrow transplantation.
AB  - Chemotherapy-induced acral erythema is a rare disorder characterized by a painful
      and intense erythema of the palms and the soles. In allogeneic bone marrow
      transplant patients, the differential diagnosis of acute graft-versus-host
      disease (AGVHD) may be difficult. We describe a case of concurrent acral erythema
      and AGVHD. The clinical features of both conditions as well as the histological
      findings on serial skin biopsy specimens are discussed.

PMID- 1388084
TI  - Impaired suppressor cell activity due to surface sulphydryl oxidation in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis is a chronic inflammatory disorder with considerable
      evidence of impaired regulation of the immune response, including defective
      suppressor cell function, especially in the synovial membrane. We have
      investigated whether oxidation of cell surface thiols might be responsible for
      these defects and whether such cell function may be modulated towards normal by
      treatment with a sulphydryl-reactive drug, D-penicillamine. Using healthy
      mononuclear cells treated with an impermeant thiol blocker, induction of
      suppressor activity by incubation with the lectin Con A was not dependent on
      surface sulphydryl groups but suppressor activity was abolished by thiol blockade
      after Con A stimulation. Peripheral blood mononuclear cells from patients with
      active rheumatoid disease showed impaired Con A-induced suppressor activity which
      was enhanced to near-normal levels by incubating the rheumatoid cells with a
      sulphydryl reducing agent, 2-mercaptoethanol, or D-penicillamine. Con A
      stimulation of cells from patients treated with intramuscular gold or D
      penicillamine generated more active suppression than those from patients
      receiving non-steroidal drugs only. Mononuclear cells from patients with other
      chronic inflammatory joint diseases showed normal Con A-induced suppressor
      activity. These data support the conclusion that surface thiols on mononuclear
      cells in rheumatoid arthritis are reversibly oxidized by the disease process.
      This gives rise to aberrant cell function including impaired suppressor activity.
      Such a mechanism may be at least partly responsible for the defective
      immunoregulation seen in rheumatoid patients and thus be a relevant target for
      thiol containing antirheumatic drugs.

PMID- 1388085
TI  - Evidence that the lateral tegmental field plays an important role in the central
      sympathoinhibitory action of 8-OH-DPAT.
AB  - We examined the effects of 8-OH-DPAT and 5-HT on three types of sympathetic
      related neurons identified in the lateral tegmental field of anesthetized cats
      using spike-triggered averaging techniques. Based on their response to
      baroreceptor activation, these neurons could be classified as sympathoexcitatory,
      sympathoinhibitory, or baroreceptor activation unresponsive. 8-OH-DPAT
      administered intravenously was found to inhibit sympathoexcitatory neurons with a
      high degree of correlation to inhibition of sympathetic activity, and to excite
      sympathoinhibitory neurons in a dose-dependent manner. Iontophoretic application
      of 8-OH-DPAT and 5-HT to the majority of sympathoexcitatory neurons caused
      inhibition of spontaneous activity while iontophoretic application of 8-OH-DPAT
      to sympathoinhibitory neurons had variable effects although 5-HT consistently
      caused excitation. Baroreceptor unresponsive neurons were insensitive to
      iontophoretic 8-OH-DPAT and showed only limited response to 5-HT. It is concluded
      that the lateral tegmental field plays an important role in the
      sympathoinhibitory action of 8-OH-DPAT.

PMID- 1388086
TI  - Amygdala kindling does not alter the N-methyl-D-aspartate receptor-channel
      complex which modulates dopamine release in the rat striatum and amygdala.
AB  - Kindling is suggested to be critically associated with enhancement of N-methyl-D
      aspartate (NMDA) type excitatory amino acid synaptic transmission. The present
      study examined effects of kindling on NMDA-induced dopamine (DA) efflux from
      slices of the rat striatum and amygdala. When assayed 5-7 days after the last
      evoked seizure, no difference was observed between kindled and non-kindled
      striatum in the ability of NMDA to induce DA release, or in the effect of MK-801
      or 7-chlorokynurenic acid to inhibit the amino acid-induced transmitter release.
      The present study revealed that NMDA receptors are also involved in the
      modulation of DA release in the amygdala. However, no difference was observed
      between kindled and non-kindled amygdala in the ability of NMDA to induce DA
      release. These results suggest that amygdala kindling does not alter activity of
      the NMDA receptor-channel complex modulating DA release in the striatum and
      amygdala.

PMID- 1388087
TI  - Effects of RPE-cell factors secreted from permselective fibers on retinal cells
      in vitro.
AB  - This study was undertaken to determine if retinal pigment epithelial (RPE) cells
      encased in permselective hollow fibers survive in a tissue culture environment
      and secrete a diffusible trophic factor(s) that may affect retinal cell survival
      in vitro. In this study, RPE cells were isolated from 6- to 8-day-old Long-Evans
      rats, then loaded into hollow fibers. The RPE-cell fibers were then cultured for
      at least one week in serum-containing medium. These RPE-cell fibers were
      subsequently co-cultured with cells isolated from retinas of day 2 Long-Evans
      rats in a defined medium. For at least 6 days in culture, opsin-positive cells
      were observed on the surface of larger flat cells. Over 80% of the small, round
      cells immunostained for opsin. However, opsin-immunostained cells were seldom
      seen in cultures with control fibers, that lacked RPE cells. In addition,
      conditioned medium collected from either the RPE-cell fibers or cultured RPE
      cells affected survival of opsin-positive retinal cells in culture in a manner
      similar to that of the RPE-cell fibers. Furthermore, selected growth factors such
      as epidermal, nerve and fibroblast growth factors, were unable to sustain retinal
      cell survival and affect morphological development as seen in RPE-CM supplemented
      cultures. In vivo companion developmental studies demonstrated that few opsin
      positive cell bodies were observed in retinas of day 2 Long-Evans rats, the age
      corresponding to the stage of retinal cell isolation. In retinas of day 5 Long
      Evans rats, the age corresponding to the end point of the in vitro assay, a
      dramatic increase in the number of opsin-immunostained cell bodies was noted,
      which corresponds to the developmental sequence also seen in culture. Light and
      electron microscopic examination revealed that the RPE cells cultured in the
      hollow tubes maintained an RPE-like structure for several months, in that these
      cells contained melanosomes and extended microvilli from their apical border and
      formed junctional complexes with adjacent cells. Results of this study confirm
      our earlier findings that RPE cells secrete an apparent novel factor(s) that
      affects retinal cell survival in vitro and, most significantly, the described
      encapsulation/secretion mechanism may provide a convenient method to deliver such
      factors for further in vivo testing of this phenomenon.

PMID- 1388088
TI  - Interleukin-1 receptor antagonist inhibits ischaemic and excitotoxic neuronal
      damage in the rat.
AB  - Interleukin-1 (IL-1) synthesis in the brain is stimulated by mechanical injury
      and IL-1 mimics some effects of injury, such as gliosis and neovascularization.
      We report that neuronal death resulting from focal cerebral ischaemia (middle
      cerebral artery occlusion, 24 h) is significantly inhibited (by 50%) in rats
      injected with a recombinant IL-1 receptor antagonist (IL-1ra, 10 micrograms, icv
      30 min before and 10 min after ischaemia). Excitotoxic damage due to striatal
      infusion of an NMDA-receptor agonist (cis-2,4-methanoglutamate) was also markedly
      inhibited (71%) by injection of the IL-1ra. These data indicate that endogenous
      IL-1 is a mediator of ischaemic and excitotoxic brain damage, and that inhibitors
      of IL-1 action may be of therapeutic value in the treatment of acute or chronic
      neuronal death.

PMID- 1388089
TI  - [Early intensification of treatment in diabetes using a combination of insulin
      and nicotinamide--effect on C-peptide levels and the course of the disease].
AB  - Significantly higher C-peptide levels were found in a group of 49 juvenile
      diabetics treated with insulin in combination with nicotinamide compared to 33
      diabetics treated with insulin only. There had been no significant differences in
      the initial values of C-peptide between the two groups. After six weeks the mean
      basal values of C-peptide in the blood of nicotinamide treated diabetics reached
      1.21 +/- 0.79 ng/ml compared to 0.87 +/- 0.55 ng/ml determined in the group
      treated with insulin only (p less than 0.05). After one year of therapy the
      differences remained significant (p less than 0.01). The insulin requirement was
      significantly lower in the nicotinamide treated group after six weeks (p less
      than 0.001) and the difference remained significant also after two years of
      nicotinamide treatment (p less than 0.02). A longer period of partial remission
      was recorded in the group of diabetics who were administered nicotinamide. (Tab.
      4, Fig. 2, Ref. 13.)

PMID- 1388090
TI  - Efficacy of ondansetron against nausea and vomiting caused by dacarbazine
      containing chemotherapy.
AB  - BACKGROUND AND METHODS: The antiemetic activity of ondansetron (Zofran, Glaxo
      Pharmaceuticals, Research Triangle Park, NC) was evaluated in 25 patients with
      recurrent melanoma who were treated sequentially with dacarbazine (DTIC),
      vinblastine, and cisplatin. The antiemetic regimen included ondansetron alone in
      11 patients; ondansetron plus lorazepam (Ativan, Wyeth-Ayerst, Philadelphia, PA)
      in 9 patients; and ondansetron plus lorazepam plus metoclopramide (Reglan, A. H.
      Robins Co., Richmond, VA) in 5 patients. Twenty-one patients had no prior
      exposure to chemotherapy, whereas 4 patients had previously received the same
      chemotherapy regimen and had severe vomiting despite administration of standard
      antiemetics. RESULTS: The antiemetic efficacy of ondansetron was impressive.
      Administration of a single dose of 10 mg resulted in complete control of nausea
      and vomiting in 22 patients, and the remaining 3 patients had only mild vomiting.
      CONCLUSIONS: Ondansetron is highly effective in controlling the nausea and
      vomiting caused by dacarbazine.

PMID- 1388091
TI  - Double-blind, parallel-group evaluation of etodolac and naproxen in patients with
      acute sports injuries.
AB  - The efficacy and safety of etodolac and naproxen were compared in a double-blind,
      randomized, parallel-group outpatient study. Patients with acute sports injuries
      were assigned to receive either etodolac 300 mg TID (50 patients) or naproxen 500
      mg BID (49 patients) for up to 7 days. Assessments were made at the pretreatment
      screening (baseline) and at days 2, 3, 4, and 7 of treatment. Assessments
      included patient and physician global evaluations, spontaneous and induced pain
      intensity, range of motion, tenderness, heat, degree of swelling, and degree of
      erythema. Safety assessments, including laboratory profiles, were made at
      pretreatment and at final evaluation; patients' complaints were elicited at all
      visits. Both treatment groups showed significant (P less than or equal to 0.05)
      improvement from baseline for all efficacy parameters by day 2 and thereafter at
      all time points. Improvement was similar for the two groups. No patients in
      either group withdrew from the study because of drug-related adverse reactions.
      The results of this study indicate that etodolac (900 mg/day) is effective and
      well tolerated as an analgesic and anti-inflammatory in acute sports injuries and
      is comparable to naproxen (1000 mg/day).

PMID- 1388093
TI  - Bioavailability of medroxyprogesterone acetate from three oral dosage
      formulations.
AB  - The bioavailability of three formulations of medroxyprogesterone acetate (MPA)
      was assessed in 30 healthy male volunteers in a three-way, open-label, cross-over
      designed trial. Each subject received one Provera 500-mg tablet, one Farlutal 500
      mg tablet, and one Provera 500-mg granule packet according to a randomized
      schedule, with each treatment separated by a 21-day washout period. Serum MPA
      levels were determined using both radioimmunoassay (RIA) and high-performance
      liquid chromatography techniques. Based on the results of RIA analysis, Farlutal
      tablets produced significantly lower serum MPA concentrations compared with
      Provera tablets at most sampling times, resulting in statistically lower AUC0-144
      for the Farlutal tablet (544 vs 768 ng.hr/ml; -29.2%). The Farlutal tablet also
      had a significantly lower maximum concentration than the Provera tablet (27.8 vs
      47.4 ng/ml; -41.4%). However, there was no significant difference in time of
      maximum concentration between the tablet formulations (3.71 vs 3.41 hr),
      indicating that the rates of absorption of the two tablet formulations were
      comparable. Provera granules provided significantly higher serum MPA levels than
      Provera tablets at 0.5, 1, 1.5, 2, and 6 hours, and the AUC0-144 for Provera
      granules was higher by 5.47% (810 vs 768 ng.hr/ml). There were no differences in
      terminal elimination rate constants among the dosage forms. No significant
      adverse events were noted during the trial. The relative bioavailabilities of
      Provera granules and Farlutal tablets were 105% and 71.2%, respectively, compared
      with Provera tablets.

PMID- 1388092
TI  - Safety and efficacy of etodolac compared with piroxicam in patients with
      degenerative joint disease of the knee.
AB  - The efficacy and safety of etodolac and piroxicam were compared in a double
      blind, randomized, parallel-group outpatient study at four sites. Patients with
      active osteoarthritis of the knee were assigned to receive etodolac 600 mg/day
      (57 patients) or piroxicam 20 mg/day (59 patients) for 6 weeks. Efficacy
      assessments were made at the pretreatment screening, at baseline, and at
      treatment weeks 2, 4, and 6 for patient and physician global evaluations, night
      pain, spontaneous pain intensity, weight-bearing pain variables, measures of
      inflammation, morning stiffness, and knee flexion. An analysis was also done
      based on each patient's final evaluation, regardless of the week at which it
      occurred. Safety assessments were made before treatment and at the completion of
      therapy. A therapeutic response was obtained in both treatment groups by the end
      of the second week of treatment. At the final evaluation, both groups showed
      significant improvement (P less than or equal to 0.05) from baseline for most
      efficacy assessments. The physician's global assessment indicated improvement in
      the condition of 60% of the etodolac-treated patients and 39% of the piroxicam
      treated patients at the final evaluation. There was no significant difference
      between treatment groups in the number of patient withdrawals due to adverse
      reactions or in the number of patients reporting side effects. The results of
      this study indicate that, compared with piroxicam 20 mg/day, etodolac 600 mg/day
      is effective and well tolerated in the treatment of patients with osteoarthritis.

PMID- 1388094
TI  - Immunological alterations in cluster headache during remission and cluster
      period. Comparison with low back pain patients.
AB  - Cluster headache is a disorder of unknown origin. Some studies have focused their
      attention on neuroendocrine derangement, others on immunity. To probe central
      alterations in cluster headache (CH), immune parameters were investigated in
      cluster headache patients in comparison to low back pain patients and healthy
      controls. Increases in peripheral blood monocytes found in remission cluster
      headache patients may be attributable to chronic central nervous system
      (hypothalamic?) noradrenergic dysfunction or altered beta-endorphin. Alterations
      in NK+, CD3+ and CD4+ levels found in cluster period cluster headache and low
      back pain patients are probably pain or stress-related.

PMID- 1388095
TI  - Regulation of retinoblastoma protein functions by ectopic expression of human
      cyclins.
AB  - The retinoblastoma susceptibility gene (RB) product, the retinoblastoma protein
      (pRb), functions as a regulator of cell proliferation. Introduction of the RB
      gene into SAOS-2 osteosarcoma cells, which lack functional pRb, prevents cell
      cycle progression. Such growth-suppressive functions can be modulated by
      phosphorylation of pRb, which occurs via cell cycle-regulated kinases. We show
      that constitutively expressed cyclins A and E can overcome pRb-mediated
      suppression of proliferation. pRb becomes hyperphosphorylated in cells
      overexpressing these cyclins, and this phosphorylation is essential for cyclin A-
      and cyclin E-mediated rescue of pRb-blocked cells. This suggests that G1 and S
      phase cyclins can act as regulators of pRb function in the cell cycle by
      promoting pRb phosphorylation.

PMID- 1388096
TI  - Apoptosis, cell proliferation and c-ras expression during and after cyproterone
      acetate (CPA) induced liver hyperplasia.
AB  - Cell proliferation and cell death appear in several systems as mutually
      exclusive, which raises the assumption that a same factor or secondary signal(s)
      might exert opposite control on the two processes. To test this assumption we
      investigated the time-course evolution of the S phase and apoptotic indices in
      rat liver during cyproterone acetate (CPA) induced hyperplasia and during the
      recovery of normal liver mass provoked, respectively, by cyproterone acetate
      (CPA) treatment and withdrawal. The levels of c-myc and c-ras transcripts were
      also followed in view of the indications of a positive role of these oncogenes in
      proliferation. The data showed that proliferation and cell death are not always
      mutually exclusive and that a high rate of cell death was indifferently
      associated with high or low c-ras expression. Our data are consistent with a role
      of this gene in proliferation but exclude that it plays an opposite role in
      controlling cell death.

PMID- 1388097
TI  - The role of heat shock protein in the persistence of arthritis.

PMID- 1388098
TI  - [Genotypes of Neisseria meningitidis strains isolated from patients in the Czech
      Republic].
AB  - A group of 75 strains of Neisseria meningitidis isolated from patients with
      meningococcal meningitis in the Czech Republic during 1980-1988 was characterized
      by assessment of serogroups, serotypes, serosubtypes and genotypes. Twelve
      strains belonged into serogroup A, 27 into serogroup B and 36 into serogroup C.
      The most frequently found serotype was 4, subserotype P1.2. The authors
      identified 48 different enzyme genotypes among which four genetically related
      groups were assessed. Strains of Neisseria meningitidis of the same genotype were
      found more frequently during the period of 1980-1984, when a rise of
      meningococcal meningitis in the Czech Republic was recorded. During this period
      73% of the strains belonged into three genetically related groups, while during
      the subsequent period (1985-1988) these genetically related groups comprised only
      47% of the strains. Only one strain of Neisseria meningitidis (878/85)
      represented a genetic clone ET-5 complex responsible for an epidemic of
      meningococcal meningitis in western European countries from the mid-seventies.

PMID- 1388099
TI  - [Levels of C-reactive protein in serum--comparison of 2 methods used for
      quantitative determination].
AB  - The authors compared the results of two methods used for the quantitative
      assessment of C-reactive protein: the method of radial immunodiffusion and the
      microturbidimetric method. The testing was based on examination of 68 sera from
      patients. The samples comprised sera with a CRP concentration under 230 mg/l.
      There was a statistically significant correlation between the results of the two
      compared methods (r = 0.949, p = 0.0001).

PMID- 1388100
TI  - [Identification of enteric bacteria using the ENTEROtest 1 and 2 and the ENTERO
      Rapid systems].
AB  - The identification efficacy of two systems, ENTEROtest 1 & 2 and ENTERO-Rapid
      (fy. Lachema a. c., Brno), was compared. A total 123 well known strains of
      enteric bacteria were tested. The ENTEROtest 1 & 2 system correctly identified
      87.0% tested strains to the species level, the ENTERO-Rapid system correctly
      identified 76.4% of these strains.

PMID- 1388101
TI  - [Diagnosis of visceral mycosis].
AB  - The author describes techniques of laboratory processing of different biological
      materials used for detection of potentially pathogenic micromycetes which are
      involved in the aetiology of secondary mycoses. The author describes in detail
      methods for the quantitative assessment of yeasts in urine and sputum.

PMID- 1388102
TI  - [Plasmid profile and toxicity of Klebsiella pneumoniae strains isolated at a
      neonatal department].
AB  - The authors tested the plasmid profile of 11 and the toxicity of 16 strains of K.
      pneumoniae isolated in a neonatal department. Based on examination of the plasmid
      profile it may be assumed that very probably a nosocomial spread of the strains
      was involved. This is suggested by the identical plasmid profile of all strains
      isolated in the environment and five strains isolated from neonates. On
      investigation of the enterotoxicity of culture filtrates of the investigated
      strains the authors did not reveal the presence of a thermolabile or thermostable
      enterotoxin. In the skin test on rabbits 93.8% of the tested samples were
      positive. Morphological changes on Vero cells after 48 hours action were produced
      by four culture filtrates. Only two strains caused haemolysis of agar with 6%
      sheep and rabbit blood after incubation at 37 degrees C. Another 14 strains
      caused lightening of the agar with rabbit blood after subsequent incubation at 4
      degrees C.

PMID- 1388103
TI  - [Diabetes and viral hepatitis B].
AB  - The author emphasizes the fact that diabetics are also in the Czech Republic a
      group with a high risk of infection with viral hepatitis type B (VHB), i. e. in
      diabetics a higher prevalence of acute VHB is found, a higher prevalence of HBsAg
      and anti-HBs, and in diabetics chronic sequelae acute hepatitis are more
      frequent. The author recommends active immunization against VHB and to focus
      attention on the group most at risk, i. e. to examine in the Czech Republic all
      diabetics treated with insulin for the presence of HBsAg and anti-HBs and to
      immunize subsequently against VHB negative subjects from this group.

PMID- 1388104
TI  - [The health impact of stray and wild cats in the human environment].
AB  - The population of stray cats in towns expands due to irresponsible behaviour of
      humans who allow them to enter cellars, hot water canals, store rooms etc. As a
      result of frequent feeding some specimens become tame, lose their shyness and on
      contact with humans and domestic animals they can become the source of some
      infectious agents. The most important of thus transmitted diseases is rabies.
      Cats become infected from foxes on rubbish heaps on the periphery of communities.
      More than 60% of cases of rabies of domestic animals are found in cats.
      Toxoplasmosis--cats excrete the infectious stage of the causal agent in their
      excreta. In the same manner also the agent causing intestinal salmonelloses is
      excreted. More than 5% cats are infected. Via excreta also the causal agents of
      toxocariasis are spread--the larvae of cat thread worms settle in the internal
      organs of humans (larva migrans). The assumed incidence in cats is as high as
      50%, as suggested also by the high positivity of specimens from children
      playgrounds. Stray cats may be the source of agents causing various
      dermatomycoses and of ectoparasites.

PMID- 1388105
TI  - [Immunologic cross reactivity of beta-lactam antibiotics].
AB  - The authors investigated the antibody response against beta-lactam antibiotics
      (penicillins, cephalosporins, monolactams, carbapenes) in conjugation with
      allergic reactions after penicillin administration. The results revealed a high
      percentage of positive antibody responses against penicillin and high percentage
      of crossed immunological reactivity between penicillin and the other investigated
      preparations.

PMID- 1388106
TI  - [Significance of hybridization methods in microbiological diagnosis: DNA probes
      and PCR].
AB  - The authors give an account of hybridization methods, in particular DNA probes
      and the polymerase chain reaction (PCR) and their application in microbiological
      diagnosis. They deal with the principle of the two methods and their applications
      in the diagnosis not only of genera and species but also different factors of
      pathogenicity and virulence. The authors mention the advantages and disadvantages
      of radioactively and non-radioactively labelled probes such as PCR. They draw
      attention to the perspective application of these methods in research and
      diagnostic laboratories.

PMID- 1388107
TI  - A single amino-acid substitution in the beta-tubulin gene of Neurospora confers
      both carbendazim resistance and diethofencarb sensitivity.
AB  - Two MBC-resistant mutants of Neurospora crassa, F914 and F939, were sensitive to
      diethofencarb at a concentration of 0.1 micrograms/ml, while the wild-type strain
      and other MBC-resistant mutants showed resistance to diethofencarb at a
      concentration of 100 micrograms/ml. Genetic analysis suggested that the mutations
      in these two strain were closely linked to the Bml locus which codes for beta
      tubulin. When the wild-type strain was transformed by the cloned beta-tubulin
      gene of the F914 strain, the transformants showed both MBC resistance and
      diethofencarb sensitivity. On the other hand, the diethofencarb sensitivity of
      the F914 strain was cancelled by transformation with the wild-type beta-tubulin
      gene. DNA sequencing of F914 beta-tubulin revealed that glycine was substituted
      for glutamic acid at position 198 in the F914 strain. Therefore, a single base
      change in the beta-tubulin gene was proved to confer both MBC resistance and
      diethofencarb sensitivity.

PMID- 1388108
TI  - Expression of Neurospora crassa laccase under the control of the copper-inducible
      metallothionein-promoter.
AB  - Laccase from the ascomycete Neurospora crassa is an inducible secretory enzyme.
      In vegetatively growing cultures its biosynthesis is repressed but can be induced
      by different protein synthesis inhibitors. Transformation of the N. crassa wild
      type strain Singapore with a fusion gene consisting of the N. crassa copper
      metallothionein promoter and the laccase gene are described in this report.
      Correct integration of the 3.6 kilobase (kb) promoter-fragment fused with the
      laccase gene containing a 5' consensus region leads to copper-dependent
      expression of the enzyme during the vegetative growth phase. The enzyme is
      glycosylated and secreted, and high amounts of extracellular activity can be
      detected. The regulation of laccase biosynthesis of one examined transformant,
      followed at both the transcriptional and the translational level, indicates co
      induction of both copper-metallothionein and laccase. The data presented show
      that expression of the recombinant laccase gene is exclusively regulated by the
      transformed N. crassa metallothionein-promoter.

PMID- 1388109
TI  - Transformants of Neurospora crassa with the nit-4 nitrogen regulatory gene: copy
      number, growth rate and enzyme activity.
AB  - nit-4 is a pathway-specific regulatory gene which controls nitrate assimilation
      in Neurospora crassa, and appears to mediate nitrate induction of nitrate and
      nitrite reductase. The NIT4 protein consists of 1090 amino-acid residues and
      possesses a single GAL4-like putative DNA-binding domain plus acidic, glutamine
      rich, and polyglutamine regions. Several mutants with amino-acid substitutions in
      the putative DNA-binding domain and a nit-4 deletion mutant, which encodes a
      truncated NIT4 protein lacking the polyglutamine region, are functional, i.e.,
      they are capable of transforming a nit-4 mutant strain. However, transformants
      obtained with most of these nit-4 mutant genes possess a markedly reduced level
      of nitrate reductase and grow only slowly on nitrate, emphasizing the need to
      examine quantitatively the affects of in vitro-manipulated genes. The possibility
      that some mutant genes could yield transformants only if multiple copies were
      integrated was examined. The presence of multiple copies of wild-type or mutant
      nit-4 genes did not generally lead to increased enzyme activity or growth rate,
      but instead frequently appeared to be detrimental to nit-4 function. A hybrid nit
      4-nirA gene transforms nit-4 mutants but only allows slow growth on nitrate and
      has a very low level of nitrate reductase.

PMID- 1388110
TI  - [Huntington's chorea from the viewpoint of forensic psychiatry].
AB  - In the initial stages Huntington's chorea is rarely correctly diagnose. The
      patient however in the early period of the illness is often subjected to social
      rejection and is more likely to be the victim of criminal acts or the perpetrator
      of such acts. The article with 3 cases studies concentrates attention to the need
      to take Huntington's chorea into consideration in determining psychiatric and
      psychological aspects of tribunals.

PMID- 1388111
TI  - Measuring unconjugated estriol in maternal serum to screen for fetal down
      syndrome.

PMID- 1388112
TI  - Effect of freezing and thawing of serum on the immunoassay of lipoprotein(a).
AB  - We studied the effect of freezing and thawing of serum on the determination of
      lipoprotein(a) [Lp(a)] with a commercial enzyme-linked immunosorbent assay
      (ELISA) and an immunoturbidimetric assay (ITA). Portions of sera from 11
      apparently healthy persons and pooled sera, from an additional 10 subjects were
      frozen at either -20 or -70 degrees C and thawed at room temperature. Cycles of
      freezing and thawing were repeated during the experiments (1 month). Samples were
      assayed for Lp(a) after thawing. Pooled sera were subjected to quick freezing at 
      70 degrees C and thawing at room temperature in cycles. Results show a
      significant (P less than 0.05) decrease in Lp(a) concentration in sera subjected
      to freezing and thawing. Samples thawed from -20 degrees C gave concentrations by
      ELISA that were significantly lower than those of fresh samples after one freeze
      thaw cycle. By ITA the decrease was significant only after two cycles. In
      specimens frozen at -70 degrees C, Lp(a) concentrations determined by ELISA
      decreased after two cycles, and by ITA after three freeze-thaw cycles. Serum
      samples subjected to quick freezing at -70 degrees C and thawing did not show
      significant decreases in Lp(a) immunoreactivity during four cycles.
      Immunoreactivity of Lp(a) in samples stored at 4 degrees C decreased after 6 days
      but fell faster in serum samples subjected to freezing and thawing before storage
      at 4 degrees C.

PMID- 1388113
TI  - Comparison of assay kits for unconjugated estriol shows that expressing results
      as multiples of the median causes unacceptable variation in calculated risk
      factors for Down syndrome.
AB  - We compared the performance of two methods for assaying unconjugated estriol in
      serum: the modified Amerlex third-trimester RIA kit, as used in seminal papers on
      unconjugated estriol in Down syndrome screening, and the new optimized Amerlex-M
      second-trimester kit. The significant difference between the results of each
      assay could cause unacceptable changes in the detection rate and false-positive
      rate of Down syndrome screening programs, especially if previously published
      values for estriol are used in the risk calculation. It is not possible to define
      new calculation parameters for every assay kit because new parameters will need
      to be defined every time kit changes occur, which would require a large
      collection of samples from Down syndrome pregnancies for standardization.
      Possible solutions to this problem are discussed.

PMID- 1388114
TI  - Rat plasma clearance rate and organ distribution of beta-hexosaminidase
      isoenzymes from human serum.
AB  - beta-Hexosaminidase (EC 3.2.1.30) is markedly increased in human serum in liver
      disease, chronic alcoholism, and pregnancy. Knowledge of the clearance rate of
      plasma/serum beta-hexosaminidase is necessary to evaluate this increase. We
      studied the plasma clearance of beta-hexosaminidase isoenzymes (purified from
      human serum and placenta) after their infusion into rat circulation. A recently
      developed enzyme immunoassay method was used to measure the human beta
      hexosaminidase isoenzymes; this method relies on both immunoreactivity and enzyme
      activity, so intact human isoenzymes were measured. In comparison with the
      placental isoenzymes (t1/2 less than 2 min), the serum forms showed a
      considerably slower clearance (t1/2 = 2-4 h). However, desialylation of the serum
      forms resulted in their rapid clearance (t1/2 less than 2 min). The organ
      localization of the enzyme eliminated from the circulation was investigated 24 h
      after infusion. Placental and native serum isoenzymes accumulated mainly in the
      liver and the spleen. Desialylated serum forms were almost exclusively localized
      to the liver.

PMID- 1388115
TI  - Amlodipine versus nifedipine retard in the treatment of chronic ischemic heart
      disease.
AB  - The efficacy of amlodipine, a long half-life dihydropyridine calcium antagonist,
      at the dosage of 5-10 mg/day in a single daily administration, has been compared
      with that of nifedipine R, a short half-life dihydropyridine, at the dosage of 20
      40 mg b.i.d. in 29 patients with chronic ischemic heart disease. After a one week
      placebo period, patients were assigned to the treatment with amlodipine or
      nifedipine R, according to a randomized sequence and a cross-over, single-blind
      design, for two control periods of four weeks and without a wash-out interval
      between these two phases. During the stress test, a significant increase from
      baseline in test duration and in time to onset of ischemia and of angina have
      been obtained with both treatments; moreover amlodipine increased significantly
      the time to onset of ST segment deviation (-1 mm) and the time to maximum ST
      segment deviation compared with nifedipine R changes. Also with Holter monitoring
      and in the angina diary there was a significant reduction of anginal episodes. As
      regards safety profile, amlodipine treatment was associated with a significantly
      lower incidence of side effects compared with nifedipine R. This is probably due
      to the particular pharmacokinetics of amlodipine which, besides the long half
      life which allows a single daily administration, shows a retarded peak (between
      the 6th and the 12th hour) with consequent reduction of phenomena connected with
      fast and excessive peripheral vasodilatation. In conclusion, amlodipine was as
      effective in reducing the signs of ischemia as nifedipine R, but compliance was
      better due to the single daily administration and so was tolerability.

PMID- 1388116
TI  - Different sensitivity of the sarcoplasmic reticulum Ca(2+)-ATPase enzyme to
      fluorescein-isothiocyanate in rabbit and carp muscles.
AB  - 1. Carp and rabbit sarcoplasmatic reticulum Ca(2+)-ATPase enzymes were compared
      with respect to their sensitivity to FITC labelling. 2. The carp enzyme showed
      much lower sensitivity to FITC in the Ca(2+)-Mg2+ activated ATPase activity.
      Fifty percent inhibition was observed at 20 microM labelling FITC concentration;
      in rabbit enzyme this inhibition was already achieved at 2 microM FITC. 3. The
      tryptic cleavage products of the carp enzyme identified with immunoblot analysis
      as well as with FITC fluorescence, suggest multiple cleavage, yielding different
      fragments from the ones well known in rabbit and in rat enzyme. 4. The present
      results indicates major structural differences with respect to the FITC binding,
      and tryptic cleavage between the SR Ca(2+)-ATPase enzymes from carp and rabbit,
      despite the cross-reactivity with polyclonal antibodies.

PMID- 1388117
TI  - Evaluating retinal circulation using video fluorescein angiography in control and
      diabetic rats.
AB  - Video fluorescein angiography has been used to evaluate retinal circulatory
      parameters in diabetic and non-diabetic Sprague-Dawley rats. Video fluorescein
      angiograms were recorded from the retina using a modified retinal fundus camera
      following a 5 ul bolus injection of sodium fluorescein dye into the jugular vein.
      Retinal circulatory parameters were measured using computer assisted image
      analysis. These analyses were performed on 25 diabetic rats with 1 week duration
      of diabetes and 26 matched, non-diabetic, rats. There was a significant (p =
      .0001) increase in retinal Mean Circulation Time (MCT) in the diabetic group
      (1.83 +/- 0.40 s) compared to the control group (1.09 +/- 0.27 s). There were no
      significant differences in arterial or venous diameters comparing diabetic and
      control groups. In a separate paired experiment, measurements were made from the
      same animals both before and after one week duration of diabetes. A paired t-test
      analysis demonstrated significantly increased MCT times in the 6 diabetic animals
      (p = .001) while there was no significant differences detected in the 4
      corresponding control animals. These results indicate that significant increases
      in retinal circulation times can be measured as early as 1 week after
      streptozotocin induced diabetes in this animal model.

PMID- 1388118
TI  - Immunohistochemical localization of basement membrane components in
      pseudoexfoliation material of the lens capsule.
AB  - The pseudoexfoliation (PSX) syndrome has long been speculated to be a disorder of
      disturbed basement membrane metabolism. To test this concept, we investigated the
      presence of all principal basement membrane components in precapsular PSX
      deposits of 30 anterior lens capsules by immunofluorescence and electron
      microscopic immunogold techniques. We have shown heparan sulfate and chondroitin
      sulfate proteoglycans, laminin, entactin/nidogen, fibronectin, and amyloid P
      protein to be an integral constituent of PSX material; type IV collagen was
      restricted to a microfibrillar layer interposed between capsular surface and
      typical PSX material. The additional presence of elastin epitopes indicates that
      the PSX material is a multicomponent expression of a disordered extracellular
      matrix synthesis including the incorporation of the principal noncollagenous
      basement membrane components. The extensive labelling of PSX material for
      chondroitin sulfate suggests an overproduction and abnormal metabolism of
      glycosaminoglycans to be one of the key changes in this disorder.

PMID- 1388119
TI  - Biological profile of the metabolites and potential metabolites of the
      anticonvulsant remacemide.
AB  - Remacemide hydrochloride ((+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)- acetamide
      hydrochloride or FPL 1292AA) is a novel compound undergoing clinical trials for
      patients with generalized tonic/clonic and complex partial epilepsy. Remacemide
      exhibits efficacy against maximal electroconvulsive shock (MES) in rodents and
      seizures elicited by N-methyl-D,L-aspartate (NMDLA) in mice. Using rat synaptic
      membrane fractions, remacemide was shown to possess relatively weak
      noncompetitive binding to the ionic channel site of the NMDA (N-methyl-D-aspartic
      acid) receptor complex. With the hypothesis that activity against NMDLA-elicited
      seizures might be reflected by transformation to a more active metabolic species,
      the aim of the present study was to evaluate potential pharmacological effects of
      the 9 identified metabolites of remacemide which were all found in human and dog
      urine. Moreover, specific entities were recognized in plasma (including the
      rat's), as well as dog and rat cerebrospinal fluid. Five putative metabolites
      were also examined. A major route of metabolic transformation of remacemide in
      rats yields the formation of a pharmacologically active more potent desglycine
      derivative, namely FPL 12495 (+/-). Potency over the parent compound is revealed
      in the MES test in mice and rats, the NMDA-induced convulsions/mortality test in
      mice, and especially involving in vitro displacement of MK801 binding to the
      channel subsite of the NMDA receptor. The S isomer (FPL 12859) of this
      desglycinate is even more potent, while the R isomer is less potent than the
      corresponding racemate. Unlike the non-competitive NMDA antagonist, MK801, these
      desglycinates did not prevent kindled seizures. Three other identified
      metabolites show efficacy in the mouse and rat in vivo tests, namely the N
      hydroxy-desglycinate (FPL 15053) and the p-hydroxy-desglycinates (FPL 14331 and
      FPL 14465). FPL 15053 exhibited modest activity in all tests. The only in vivo
      activity exhibited by the 2 p-hydroxy-desglycinates was evidenced in the MES test
      following i.p. and i.v. dosing. However, FPL 14331 was active in the MK801
      binding assay. An oxoacetate metabolite, PFL 15455, failed to demonstrate any
      biological activity. Of potential metabolites tested 2 beta-hydroxy-desglycinates
      (FPL 14991 and FPL 14981) displayed modest activity in the MES test, however,
      only FPL 14981 prevented NMDLA-induced convulsions/mortality in mice and was 2
      fold more active regarding MK801 binding. The hydroxy-methyl derivative of
      remacemide (FPL 13592) and its desglycinate (FPL 15112) prevented MES-induced
      convulsions only after i.v. administration; only the desglycine derivative
      displaced MK801 binding.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1388120
TI  - Teicoplanin plus ciprofloxacin versus gentamicin plus piperacillin in the
      treatment of febrile neutropenic patients.
AB  - Teicoplanin plus ciprofloxacin was compared with gentamicin plus piperacillin for
      the empirical treatment of fever in 80 neutropenic patients. A favourable
      response was seen in 78% of patients receiving teicoplanin plus ciprofloxacin and
      in 49% receiving gentamicin plus piperacillin (p less than 0.05). When
      microbiologically documented episodes were analysed separately, the response to
      teicoplanin plus ciprofloxacin was favourable in 81% of patients whereas only 35%
      responded favourably to gentamicin plus piperacillin (p = 0.034). Gram-positive
      organisms accounted for 76% of bacterial isolates, Staphylococcus epidermidis
      being the most common pathogen. Ten of 12 (83%) Staphylococcus epidermidis
      infections resolved when treated with teicoplanin plus ciprofloxacin as compared
      with 2 of 8 (25%) treated with gentamicin plus piperacillin. Teicoplanin is at
      least as effective as gentamicin plus piperacillin in the empirical treatment of
      febrile neutropenic patients and may be more effective in situations where gram
      positive organisms are prevalent. The high incidence of gram-positive infections
      in our unit justifies the use of an agent with specific activity against gram
      positive organisms in the first-line antibiotic regimen.

PMID- 1388121
TI  - Effect of amperozide on rat cortical 5-HT2 and striatal and limbic dopamine D2
      receptor occupancy: implications for antipsychotic action.
AB  - Amperozide (FG 5606, N-ethyl-4-[4',4'-bis(p-fluorophenyl)butyl]-1-piperazine
      carboxamide) is an atypical antipsychotic drug which has relatively weak in vitro
      affinity for striatal dopamine2 (D2) receptors and strong affinity for cortical 5
      HT2 receptors. The in vivo affinity for 5-HT2 binding sites in rat cortex was 1.1
      mg/kg. In striatum or olfactory tubercle, doses of amperozide up to 40 mg/kg did
      not displace radioligand binding to D2 receptors. Amperozide, haloperidol and
      ritanserin had similar in vivo potency in blocking the 5-HT2 binding site, but
      only haloperidol displaced D2 receptor binding. Based on the clinically effective
      dose of amperozide (0.14-0.28 mg/kg per day), it is suggested that the
      antipsychotic effect of amperozide is related, in part, to its in vivo
      interaction with the 5-HT2 receptor and that amperozide cannot be expected to
      exert its antipsychotic action by blockade of D2 receptors in the striatum or
      limbic regions.

PMID- 1388122
TI  - Endogenous secretin in the rat--evidence for a role as an enterogastrone but
      failure to influence serum calcium homeostasis.
AB  - The release of secretin into plasma by intraduodenal (id) infusion of HCl or iso
      osmotic (290 mosm l-1) NaCl, and the associated changes of moderately stimulated
      gastric acid, serum gastrin, two calciotropic hormones, total and 45calcium (Ca),
      were examined in the rat. The possible role of endogenous secretin as an
      enterogastrone and as a mediator of the hypothesized endocrine gut-thyroid
      parathyroid axis was further characterized with the aid of secretin
      immunoneutralization and exogenous secretion. The id-HCl-stimulated secretin,
      measured by a sensitive radioimmunoassay, was accompanied by a decrease in
      gastric acid secretion, whereas secretin blockage by anti-secretin immune serum
      resulted in a significant increase in acid secretion. The correlation between
      plasma secretin and acid output was only slight. Gastrin and Ca metabolism
      remained unchanged during secretin stimulation. Intravenous synthetic porcine
      secretin at a dose reported to be effective in other target preparations (2 CU
      (0.58 microgram) kg-1 h-1) had no effect on gastric acid secretion and Ca
      metabolism. In contrast, a pharmacological dose, 32 CU (9.3 micrograms) kg-1 h-1,
      inhibited acid secretion, decreased serum Ca and total protein, and increased
      serum parathyroid hormone, but left calcitonin and gastrin unchanged. Endogenous
      secretin appeared to act as an enterogastrone, but whether it was the only one is
      unclear. No role was detected for secretin in the gut-thyroid-parathyroid axis,
      since the Ca changes observed may have been unspecifically mediated.

PMID- 1388123
TI  - Homologous sucrose synthase genes in barley (Hordeum vulgare) are located in
      chromosomes 7H (syn. 1) and 2H. Evidence for a gene translocation?
AB  - The chromosomal location of the two types of sucrose synthase genes, Ss1 and Ss2,
      has been investigated in barley by Southern blot analysis of wheat-barley
      addition lines using non-cross-hybridizing-specific probes corresponding to the C
      terminal regions of their respective cDNA clones (congruent to 250 bp). The Ss1
      gene, whose cDNA of 2,667 bp has been entirely sequenced, is located in the beta
      arm of chromosome 7H (syn. 1), while that corresponding to the homologous Ss2 is
      in the short arm of 2H, suggesting the existence of a translocation event between
      these two chromosomes in cultivated barley after an initial gene duplication and
      divergent evolution.

PMID- 1388124
TI  - System A transport activity is stimulated in skeletal muscle in response to
      diabetes.
AB  - We have studied the activity of system A transport in skeletal muscle during
      experimental diabetes. Five days after streptozotocin injection, rats showed a
      marked hyperglycemia and a substantial decrease in the content of GLUT-4 protein
      in skeletal muscle and adipose tissue. Under these conditions, basal uptake of 2
      (methyl)aminoisobutyric acid (MeAIB), an index of system A transport activity,
      was enhanced in extensor digitorum longus (EDL) muscles from diabetic rats
      compared to controls. Furthermore, insulin-stimulated MeAIB uptake by the
      incubated EDL and soleus muscles was markedly greater in diabetic than in control
      rats. The derepressive phase of adaptive regulation was partially blocked in the
      diabetic muscle, and incubation of muscles for 3 h in the absence of amino acids
      led to a lower stimulation of system A transport activity in muscles from
      diabetic groups compared to controls. We propose that the activated system A
      might participate in the enhanced alanine release from muscle cells that occurs
      in diabetes.

PMID- 1388125
TI  - Human interleukin-1 receptor antagonist. High yield expression in E. coli and
      examination of cysteine residues.
AB  - The human IL-1 receptor antagonist (IL-1ra) was produced in a high yield E. coli
      expression system, and was purified in a rapid two-step purification. This
      recombinant IL-1ra molecule possessed full binding activity to the IL-1 receptor
      (type I) and totally inhibited IL-1-induced PGE2 production by human dermal
      fibroblasts. Radioalkylation and analysis of V8-derived IL-1ra peptides indicate
      that the four cysteines present in the IL-1ra are not disulphide-linked.

PMID- 1388126
TI  - Changes in blood coagulation, platelet function, and plasminogen-plasmin system
      in diabetes.
AB  - The increased risk of thromboembolism in people with diabetes mellitus is in part
      due to changes in the hemostatic mechanism including abnormal platelet function
      leading to platelet activation, increase in several coagulation factors, decrease
      in natural anticoagulants, and impaired fibrinolytic activity. Both
      microangiopathy and atherosclerosis in people with diabetes will enhance the
      thrombotic potential of these abnormal hemostatic changes. The recent recognition
      of a role of the components of the plasminogen-plasmin system in many biologic
      functions at the cellular level has led to studies showing that the angiopathic
      complications of diabetes may also be caused by impaired plasminogen activator
      function.

PMID- 1388127
TI  - The promise of independence.

PMID- 1388128
TI  - [Asthma and skin rash after preparation to colonoscopy with a flavored
      polyethylene glycol solution].

PMID- 1388129
TI  - Incidence of two virulence factors (aerobactin and mucoid phenotype) among 190
      clinical isolates of Klebsiella pneumoniae producing extended-spectrum beta
      lactamase.
AB  - Because outbreaks of multiple-resistant Klebsiella pneumoniae isolates producing
      extended-spectrum beta-lactamases were recently observed in French hospitals, the
      presence of virulence factors was examined for (i) phenotype by bioassay for
      aerobactin production and by culture for the mucoid phenotype, and (ii) genotype
      using intragenic probes of respectively 2-kb BglII and 235-bp BamHI-BglII
      fragments and dot-blotting among 190 unreplicated K. pneumoniae clinical isolates
      issued from 25 French hospitals and producing different types of extended
      spectrum beta-lactamases (TEM-related enzymes: TEM-3, TEM-4, CAZ-1, CAZ-2, TEM-8,
      or SHV-related enzymes: SHV-2, SHV-3, SHV-4). Only 3.7% and 7% of K. pneumoniae
      isolates produced aerobactin and mucoid phenotypes respectively, unrelated to
      type of beta-lactamase. Only 2% had both factors. No discordance was reported
      according to the detection method tested. The low prevalence of such virulence
      factors seems to indicate they were not involved in dissemination of nosocomial
      K. pneumoniae isolates producing an extended-spectrum beta-lactamase.

PMID- 1388130
TI  - [Effects of air pollution on the prevalence of pollinosis in children in the
      southern region of Kazakhstan].

PMID- 1388132
TI  - Pelviscopic treatment of ovarian cysts in premenopausal women.
AB  - Between 1984 and 1989, 773 patients less than or equal to 45 years of age,
      presenting with a total of 809 ovarian cysts, underwent pelviscopy at the
      Department of Obstetrics and Gynecology of Kiel University. In 36 cases, cysts
      were bilateral. 678 cysts (84%) were treated by pelviscopy alone. Organ
      preserving treatment was performed in 83%, oophorectomy or adnexectomy in only
      17% of cases. Two stage Ia ovarian carcinomas (0.26% of all cysts) were operated
      on by pelviscopy before laparotomy. Sonography is particularly important in
      determining whether a pelviscopic approach is appropriate. Pelviscopic procedures
      are unacceptable in multilocular cysts measuring greater than or equal to 7 cm in
      diameter with echo-dense components. Special caution is required for any cyst
      measuring greater than 9 cm in diameter. The risk of opening a malignant cyst
      must be weighed against the advantages of pelviscopic surgery: minimal physical
      strain, better postoperative quality of life, and organ conservation. In doubtful
      cases, laparotomy is recommended.

PMID- 1388131
TI  - Chemosensitizing effect of an antiestrogen, toremifene, on ovarian cancer.
AB  - The chemosensitizing effect of an antiestrogen, toremifene, was studied on 2
      human ovarian cancer cell lines in vitro and on 3 fresh surgical ovarian tumor
      explants with the aid of the subrenal capsule assay (SRCA). Also, 11 patients
      with secondarily drug resistant, recurrent gynecologic cancer (8 ovarian and 3
      uterine cancers) were treated with 240 mg toremifene daily for 1 week before each
      course of cytostatics. Toremifene potentiated the effect of doxorubicin on both
      cell lines. This was also the case on 1 cell line that was not completely
      resistant to doxorubicin. The SRCA showed a clear potentiating effect of
      toremifene only on the tumor overtly resistant to the combination of cisplatin,
      doxorubicin, and cyclophosphamide. Of the 11 patients treated with toremifene and
      cytostatics, the response of 8 patients was evaluable: 3 had partial response, 3
      no change, and 2 progressive disease. Toremifene seems to have a
      chemopotentiating effect on gynecologic drug-resistant tumors.

PMID- 1388133
TI  - Abnormal cardiovascular responses induced by localized high power microwave
      exposure.
AB  - A hypothesis of microwave-induced circulatory under perfusion was tested in
      ketamine anesthetized rats whose heart rate, mean arterial pressure, pulse
      pressure, respiration rate, and body temperatures were monitored continuously.
      Fifty-eight ventral head and neck exposures in a waveguide consisted of sham
      exposure and exposure to continuous wave (CW) and pulsed 1.25 GHz microwaves for
      5 min. The 0.5 Hz (10 microseconds, 2 W average) and 16 Hz (1 microsecond, 6.4 W
      average) pulse-modulated microwaves were delivered at 400 kW peak power. The CW
      microwaves were 2 and 6.4 W. The average specific absorption rate was 4.75 W/kg
      per watt transmitted in the brain and 17.15 W/kg per watt transmitted in the
      neck. Respiration rate and mean arterial pressure were not altered. Changes in
      heart rate and pulse pressure were observed in rats exposed to higher power (16
      Hz pulses and 6.4 W CW) but not to the lower average power microwaves (0.5 Hz
      pulses and 2 W CW). Depression of pulse pressure, an indication of a decrease in
      stroke volume, and increased (tachycardia) or decreased (bradycardia) heart rate
      were noted in presence of whole-body hyperthermia. The cardiac output of those
      animals exposed to higher average power microwaves was considered to be below
      normal as hypothesized. Decreased cardiac output and normal mean arterial
      pressure resulted in an increase in the total peripheral resistance which was
      contrary to the anticipated thermal response of animals.

PMID- 1388134
TI  - Complement activation in the follicular light zone of human lymphoid tissues.
AB  - A comparative immunohistochemical study of the distribution pattern of complement
      components and regulatory proteins within secondary lymphoid follicles was
      performed by the immunoperoxidase technique. Fifteen lymphoid tissues including
      appendices. Peyer's patches and tonsils were analysed. Sixty secondary lymphoid
      follicles with evident polarity, that is, the distinct coexistence of a light
      zone, dark zone and mantle zone in the same lymphoid follicle, were tested with
      single antibodies. The light zones were consistently immunostained in a dendritic
      meshwork pattern with all antibodies. The immunostaining patterns were classified
      into two major groups based on the immunoreactivity of the dark zone. One
      immunostaining pattern was characterized by no immunostaining of the dark zone to
      the majority of the antigens. The second group was characterized by a diffusely
      weak to moderate dendritic meshwork pattern of the dark zone to some of the
      immunostainings of C9 (monoclonal), S-protein, and DF-DRC1, and all
      immunostainings of CR1 (CD35), Ber-Mac-DRC (CD35), CR2 (CD21), and R4/23. All
      four complement regulatory proteins were localized by immunoelectron microscopy
      attached to the cell surface of the cells, including follicular dendritic cells,
      in the light zone. Our data indicate that there is an evident functional
      difference between the light zone and the dark zone, and that complete activation
      of the complement system occurs only in the light zone.

PMID- 1388135
TI  - Occupancy of CD72 (the CD5 counterstructure) enhances interleukin-4-dependent
      CD23 expression in resting B lymphocytes.
AB  - CD72, the human homologue of murine Lyb-2, was recently identified as a
      counterstructure to CD5. An antibody to CD72 (BU40) has been found to mimic
      interleukin-4 (IL-4) both in its ability to activate resting B cells into the
      early G1 phase of cell cycle and to augment the expression of major
      histocompatibility complex (MHC) class II antigen; unlike IL-4, the CD72
      clustered antibody fails to induce the expression of CD23. We now report that
      engagement of CD72 by the IgG monoclonal antibody BU40 potentiates the capacity
      of IL-4--when used at optimal concentrations--to promote CD23 production in human
      B cells. The degree of enhancement arising from occupancy of CD72 ranged from two
      to fivefold. Importantly, antibody to CD72 was also found to diminish the
      concentration required for IL-4 to promote CD23 expression to a level equivalent
      to that maximally achieved when using IL-4 alone. Engagement of CD72 by BU40 not
      only increased the amount of cell-associated CD23 induced by IL-4 but also led to
      augmented release of soluble material into the culture medium. Monovalent Fab
      fragments of BU40 antibody were as efficient as intact antibodies at synergizing
      with IL-4 for enhanced expression and release of CD23: thus simple tethering
      without the need for receptor cross-linking was sufficient to invoke change
      through CD72. Enhancement of CD23 expression via CD72 appeared to be selective
      for IL-4-dependent induction: the turn on of CD23 by tumour-promoting phorbol
      ester was left unaltered on the addition of BU40 antibody. Engagement of CD72 had
      no effect on the IL-4-promoted hyperexpression of surface IgM. The findings are
      discussed within the context of the molecular and functional interactions
      occurring during T-B collaboration.

PMID- 1388136
TI  - Phorbol ester synergizes with Ca2+ ionophore in activation of protein kinase C
      (PKC)alpha and PKC beta isoenzymes in human T cells and in induction of related
      cellular functions.
AB  - Studies described herein were designed to examine the effects of 12-O
      tetradecanoyl phorbol-13-acetate (TPA), and a Ca2+ ionophore (ionomycin), singly
      or in combination, on the activation and expression of the Ca(2+)-dependent
      protein kinase C (PKC) isoenzymes (alpha, beta and gamma) at the protein and
      messenger RNA (mRNA) levels in T cells. These two agents induce the activation
      and proliferation of T lymphocytes by mimicking the action of inositol
      phospholipid-derived second messengers normally generated by triggering of the
      antigen-specific T-cell receptor (TcR)/CD3 complex. TPA-induced T-cell
      proliferation, expression of interleukin-2 receptor-alpha subunit (IL-2R alpha)
      and transferrin receptor, CD3 down-regulation and, lastly, the cytosol-to
      membrane PKC translocation (determined by an enzymatic assay or by immunoblotting
      with a cross-reactive anti-PKC peptide antibody) were all facilitated by
      ionomycin. Immunoblots with isoenzyme-specific anti-PKC monoclonal antibodies
      demonstrated expression of immunoreactive PKC alpha, PKC beta and PKC gamma
      proteins that were translocated to the membrane upon TPA plus ionomycin
      stimulation. Resting T cells expressed abundant levels of mRNA for PKC alpha and
      PKC beta, but very low levels (relative to brain) of PKC gamma. TPA increased by
      two- to threefold the expression of PKC beta, but not of PKC alpha or PKC gamma,
      mRNA within 12 hr of stimulation. Ionomycin synergized with TPA in increasing the
      expression of PKC alpha and PKC beta mRNA. The two agents also synergized in
      inducing expression of additional activation/growth-associated genes, namely the
      c-myc protooncogene, ornithine decarboxylase (ODC) and IL-2R alpha. Ionomycin
      alone was inactive (or marginally active) in all of these assays. The
      translocation of distinct Ca(2+)-dependent PKC isoenzymes to the membrane and the
      up-regulation of PKC alpha and beta mRNA suggest that at least these two
      isoenzymes are involved in discrete steps of the pathway leading to T-cell
      activation and proliferation. Moreover, the combined effects of TPA and ionomycin
      on T-cell function and cell-surface antigen expression appear to be due, at least
      in part, to their synergistic activation of distinct PKC isoenzyme(s).

PMID- 1388137
TI  - Altered patterns of glycosylation on rat lymphocytes associated with activation.
AB  - The expression of cell-surface carbohydrates on rat lymphocytes was investigated
      by flow cytometry using a panel of lectins. A small group of lectins was
      identified, all with a main binding requirement of N-acetylgalactosamine that
      bound to all B lymphocytes but only to activated T lymphocytes expressing the
      interleukin-2 (IL-2) receptor (as shown by staining with the monoclonal antibody
      OX39). Studies demonstrated that five of these lectins competed for the same
      binding site, while others did not. With the knowledge of the binding
      requirements of these lectins, a structure can be deduced for the carbohydrate
      moiety which appears on T lymphocytes when activated.

PMID- 1388138
TI  - Interleukin-5 increases the expression of alkaline phosphatase activity in murine
      B lymphocytes.
AB  - Interleukin-5 (IL-5) was shown to enhance, in a dose-dependent fashion, the
      expression of alkaline phosphatase (APase) activity in splenic B cells stimulated
      with dextran sulphate (DXS). The potentiating effect of IL-5 was still more
      evident when assayed in large B cells than in small resting B cells, whereas IL
      2, IL-4 and IL-6 were devoid of activity. Concomitant with increased APase
      expression, cell-cycle analysis by flow cytometry showed that large B cells in
      the early G1 phase were stimulated by IL-5, in conjunction with DXS, to enter G1B
      and to progress further through S and G2/M. A phosphorylation-dephosphorylation
      pathway could, thus, be involved in IL-5 transmembrane signalling.

PMID- 1388140
TI  - Influence of cefodizime on the reagibility of human leukocytes.
AB  - Cefodizime was evaluated for its effect on a number of parameters of leukocyte
      function in humans. Four healthy volunteers received 2 g i.v. b.i.d. for seven
      days. Leukocyte activity was measured before, during and after treatment. Using
      opsonized zymosan as a stimulant, no effect on the respiratory burst of
      granulocytes was observed. It was found, however, that the lymphocytes in three
      of the four subjects showed significantly more marked proliferation rates in the
      mixed lymphocyte reaction after administration of cefodizime than at baseline.
      The stimulation indices subsequently returned to normal. This pilot study
      therefore demonstrated that cefodizime has biological response modifying
      properties in healthy humans.

PMID- 1388139
TI  - Expression of mouse Tla region class I genes in tissues enriched for gamma delta
      cells.
AB  - The Tla region of the BALB/c mouse major histocompatibility complex contains at
      least 20 class I genes. The function of the products of these genes is unknown,
      but recent evidence demonstrates that some Tla region gene products could be
      involved in presentation of antigens to gamma delta T cells. We have generated a
      set of polymerase chain reaction (PCR) oligonucleotide primers and hybridization
      probes that permit us to specifically amplify and detect expression of 11 of the
      20 BALB/c Tla region genes. cDNA prepared from 12 adult and fetal tissues and
      from seven cell lines was analyzed. In some cases, northern blot analysis or
      staining with monoclonal antibodies specific for the Tla-encoded thymus leukemia
      (TL) antigen were used to confirm the expression pattern of several of the genes
      as determined by PCR. Some Tla region genes, such as T24d and the members of the
      T10d/T22d gene pair, are expressed in a wide variety of tissues in a manner
      similar to the class I transplantation antigens. The members of the TL antigen
      encoding gene pair, T3d/T18d, are expressed in only a limited number of organs,
      including several sites enriched for gamma delta T cells. Other Tla region genes,
      including T1d, T2d, T16d, and T17d, are transcriptionally silent and transcripts
      from the T8d/T20d gene pair do not undergo proper splicing. In general, sites
      that contain gamma delta T lymphocytes have Tla region transcripts. The newly
      identified pattern of expression of the genes analyzed in sites containing gamma
      delta T cells further extends the list of potential candidates for antigen
      presentation to gamma delta T cells.

PMID- 1388142
TI  - A survey of handicapped people in Saone-et-Loire (France).

PMID- 1388141
TI  - Identification of childhood disability in Jamaica: the ten question screen.
AB  - This is the first in a series of papers that report the testing of two
      instruments for the identification and assessment of childhood disability by
      community workers (CWs) in Third World countries. It is part of the International
      Epidemiologic Study on Childhood Disability. The Ten Question Screen (TQ) was
      used as the main instrument to identify disability in a two stage population
      based survey of 5478 children aged 2-9 years in Clarendon, Jamaica. In the second
      stage, TQ positive and 8% of the screen negative controls were professionally
      assessed by a doctor and a psychologist using standard criteria based on the main
      classification system of the ICIDH. Sensitivity of the TQ as a whole varied in
      different strata of the group and amongst different disabilities, from perfect in
      girls under 6 years, fits and motor disabilities and for serious disability in
      all group except boys over 5 years with cognitive disability. Specificity was
      good but the false positive rate was unacceptably high at 74%. It was concluded,
      firstly, that the validation of a simple questionnaire of perceptions of
      behaviour against objective measurements of impairments was perhaps not fair to
      the TQ. In spite of this, the TQ would be a very useful instrument in collecting
      disability data or for identifying people in need of rehabilitation help, if a
      way of reducing false positives could be found.

PMID- 1388143
TI  - Parent evaluation of community based rehabilitation in Jamaica.

PMID- 1388144
TI  - The cancer-associated retinopathy antigen is a recoverin-like protein.
AB  - Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration that
      occurs in association with certain forms of cancer. CAR patients typically
      possess high titers of autoantibodies against a specific photoreceptor protein-
      the 23 kD retinal CAR antigen. The mechanisms involved in the vision loss
      experienced by CAR patients are not understood, but serologic studies indicate
      the process could include a series of autoimmune reactions directed at specific
      components of the retina. Because the retinal CAR antigen is the principal ocular
      autoantigen involved in the antibody response of CAR patients, characterizing it
      would contribute to the understanding of putative autoimmune involvement. Serum
      antibodies from CAR patients have been used to isolate the gene encoding the CAR
      antigen from a cDNA library of human retina. Nucleotide sequence analysis
      suggests that the CAR antigen shows approximately 90% homology to the published
      amino acid sequence of bovine recoverin.

PMID- 1388145
TI  - Alterations in ascorbic acid transport into the lens of streptozotocin-induced
      diabetic rats and guinea pigs.
AB  - High ascorbic acid (AA) levels in the aqueous humor and intraocular tissues,
      including the lens, are thought to protect against the harmful effects of
      photochemical and ambient oxidation reactions involving oxygen and its radicals.
      In addition, AA may have various metabolic functions, including structural
      collagen formation in intraocular tissues. Recent work showed that, in the guinea
      pig, reduced AA was concentrated in the aqueous and lens epithelium. These in
      vivo studies were extended to streptozotocin-induced diabetic rats and guinea
      pigs to explore the state of AA transport and passive L-glucose movement in the
      diabetic lens. A bolus dose of radiolabeled test molecules, including 14C-AA, 3H
      L-glucose (L-glu), and 14C-3-O-methyl-D-glucose, was injected into the blood at
      time zero, and the time-dependent concentrations of these labeled molecules were
      determined as they move into the aqueous humor, lens epithelium and capsule, and
      interior compartments. These kinetic studies provided a unique measurement of the
      functioning state of passive and carrier transport mechanisms in situ in normal
      and diabetic animals. Diabetic animals (blood glucose, greater than 300 mg/dl)
      were categorized in terms of the length of time of uniform monitored drug-induced
      diabetes as short term (10-20 days); midterm (40-60 days), and long term (100+
      days). In the rat lens epithelium, significant decrease occurred in the active
      movement of AA (control KEi, 0.693 +/- 0.062 [n = 12]; midterm drug-induced
      diabetes Ki, 0.192 +/- 0.054 [n = 10]; t-test P less than 0.001). The passive L
      glu entry rate increased (control KEi, 0.0268 +/- 0.0053 [n = 12]; midterm drug
      induced diabetes KEi, 0.0421 +/- 0.075 [n = 10]; t-test P less than 0.005). Thus,
      it was suggested that the drug-induced diabetic rat lens epithelium had lost some
      of its ability to concentrate AA to high levels and achieved epithelial levels
      only one- to twofold those of aqueous; control animals concentrated AA to levels
      of five- to eightfold those of aqueous within 20 min. By contrast, the rate of
      movement of L-glu from epithelium to stroma increased minimally (control KSi,
      0.0116 +/- 0.021 [n = 12]; midterm drug-induced diabetes KSi, 0.0136 +/- 0.034 [n
      = 10]; t-test P less than 0.05). In addition, AA entry rate into lens cortex
      increased fourfold (control KSi, = 0.0018 +/- 0.0003 [n = 12]; midterm drug
      induced diabetes KSi, 0.0081 +/- 0.024 [n = 10]; t-test P less than
      0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1388146
TI  - The transformation-defective adenovirus 12 host range mutant CS-1 lacks the E1a
      specific 9.5S mRNA and contains a second deletion in E1b.
AB  - We have further analyzed structure and expression of the E1 region of the
      transformation-defective adenovirus 12 (Ad12) host range mutant CS-1. Using cDNA
      polymerase chain reaction analysis, the E1a region was found to give raise to
      five transcripts analogous to the Ad12wt 13S, 12S, 11S, 10S species and the
      normal 9S mRNA. Due to loss of a splice acceptor site at position 852, the Ad12wt
      specific 9.5S transcript cannot be synthesized by the mutant CS-1. The fact that
      the virus is, however, completely viable indicates that this mRNA is dispensable
      for lytic growth of Ad12. Besides the deletions in E1a described previously, a
      second deletion of 31 base pairs was found in the E1b gene. It affects the start
      site of the E1b-specific mRNAs and destroys or eliminates the AUG sequence for
      the E1b 19-kD protein. As shown earlier, normal E1b mRNA expression is found in
      mutant-infected cells, but no 19-kD E1b protein was immunoprecipitated by an E1
      specific rat tumor serum.

PMID- 1388147
TI  - Mycotoxins and reproduction in domestic livestock.
AB  - Molds are parasitic plants that are ubiquitous in livestock feedstuffs. Even
      though molds themselves reduce the quality of grains, their synthesis of chemical
      substances termed mycotoxins causes the greatest monetary loss to the animal
      industry. Five major mycotoxins that impair growth and reproductive efficiency in
      North America are aflatoxins, zearalenone, deoxynivalenol, ochratoxin, and ergot.
      Aflatoxins are produced by Aspergillus flavus and Aspergillus parasiticus.
      Consumption of grains containing aflatoxins by swine affects reproduction
      indirectly by reducing feed intake and growth. In swine, aflatoxins impair liver
      and kidney function, delay blood clotting, increase susceptibility to bruising,
      and interfere with cellular humoral immune systems. Ruminants are comparatively
      resistant to aflatoxicosis, but presence of aflatoxins in milk of dairy cows is
      closely monitored for human safety. Depending on environmental conditions,
      Fusarium roseum can produce either zearalenone or deoxynivalenol. Days 7 to 10
      postmating seem to be a critical period of gestation for zearalenone to exert its
      detrimental actions on early embryonic development. Presence of deoxynivalenol in
      swine feedstuffs decreases feed intake, causes feed refusal, and induces
      occasional vomiting. Several species of Penicillium and Aspergillus produce
      ochratoxin, a mycotoxin that causes necrosis of kidney tissue. Ergot alkaloids
      produced by Claviceps purpurea on wheat can cause reproductive problems and are
      associated with lactational failure in swine. Various methods have been developed
      to remove mycotoxins from infected feedstuffs. Chemical analyses in laboratories
      as well as diagnostic kits suitable for use at the elevator or farm can be used
      successfully to identify which mycotoxins are present in suspect feedstuffs.

PMID- 1388148
TI  - Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb
      suspension.
AB  - Morphological and enzymatic responses in fibers expressing fast, slow, or both
      types of myosin heavy chain (MHC) were studied in rats after 14 days of
      spaceflight (COSMOS 2044) or hindlimb suspension. Although the percentage of slow
      twitch fibers was unchanged, a higher percentage of fibers that expressed both
      slow and fast MHC was observed in flight and suspended rats than in synchronous
      ground-based controls. The soleus was 25 and 34% smaller than control after 14
      days of flight and suspension, with the reduction in fiber cross-sectional area
      (CSA) being greater in slow- than in fast-twitch fibers in both experimental
      groups. The activities of succinate dehydrogenase (SDH) and alpha
      glycerophosphate dehydrogenase (GPD) were not significantly affected by flight or
      suspension. The total SDH activity (i.e., SDH activity x CSA) decreased
      significantly in the slow-twitch fibers of the flight and the fast-twitch fibers
      of the suspended rats, in large part due to fiber atrophy. A shift in MHC
      expression in 14 and 9% of the fibers in flight and suspended rats occurred
      without a change in myosin adenosinetriphosphatase activity. The SDH and GPD
      activities of the fibers that expressed both slow and fast MHC were slightly
      higher than the slow-twitch fibers and slightly lower than the fast-twitch
      fibers. These data indicate that events were initiated within 14 days of
      spaceflight or suspension that began to reconfigure the protein profiles of 9-14%
      of the slow-twitch fibers from typical slow-twitch toward those of fast-twitch
      fibers, while all fibers were dramatically losing total protein.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1388149
TI  - Adaptation of fibers in fast-twitch muscles of rats to spaceflight and hindlimb
      suspension.
AB  - The adaptation of single fibers in medial gastrocnemius (MG), a fast-twitch
      extensor, and tibialis anterior (TA), a fast-twitch flexor, was studied after 14
      days of spaceflight (COSMOS 2044) or hindlimb suspension. Cross-sectional area
      (CSA) and succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase
      (GPD), and myofibrillar adenosinetriphosphatase (ATPase) activities were
      determined in fibers identified in frozen serial cross sections. Fibers were
      categorized as light, dark, or intermediate on the basis of myosin ATPase
      staining and alkaline preincubation and immunohistochemically as reacting with
      slow, fast, or both slow and fast myosin heavy chain monoclonal antibodies.
      Because there was a close relationship between these two means of categorizing
      fibers, all fibers were categorized on the basis of the immunohistochemical
      reaction. The percentage of slow- and fast-twitch fibers of the MG and TA were
      unchanged in either group. Mean fiber size of all fibers, irrespective of type,
      was unaffected in either muscle after flight or suspension. The fibers that
      expressed both fast and slow myosin heavy chains were smaller than control in the
      MG of both experimental groups. Compared with control, the SDH and total SDH
      activities in the MG were significantly less in suspended rats, with the fast
      twitch fibers showing the largest difference. The ATPase activity in the MG was
      higher in flight than in control or suspended rats. There were no significant
      effects of flight on fibers of the TA. In contrast, the TA in suspended rats had
      higher GPD activities than either control or flight rats.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1388150
TI  - Effects of microgravity and tail suspension on enzymes of individual soleus and
      tibialis anterior fibers.
AB  - Selected enzymes of energy metabolism were measured in random individual fibers
      of soleus and tibialis anterior (TA) muscles from rats exposed for 2 wk to
      spaceflight (F) aboard COSMOS 2044 or tail suspension (T) and from synchronous
      controls. Average size of soleus fibers (dry weight per unit length) was reduced
      37% in F and T fibers; there was little change in TA fibers. Enzyme changes were
      more pronounced in soleus than in TA fibers. Three enzymes characteristic of fast
      twitch muscles, pyruvate kinase, glycerol-3-phosphate dehydrogenase, and 1
      phosphofructokinase, were elevated in F and T soleus fibers, but changes in
      phosphofructokinase were not statistically significant. 3-Ketoacid-CoA
      transferase, characteristic of slow-twitch muscles, did not change significantly
      in either F or T fibers. Hexokinase, usually moderately higher in slow- than in
      fast-twitch muscles, increased markedly in both F and T fibers. In TA fibers
      analyzed for hexokinase, malate dehydrogenase, phosphohexoisomerase, and pyruvate
      kinase, only hexokinase and malate dehydrogenase showed significant changes.
      Hexokinase increased 83% in one of two T muscles. Enzyme data for TA fibers typed
      by myosin adenosinetriphosphatase were more informative: phosphofructokinase,
      phosphorylase, and glycerol-3-phosphate dehydrogenase were increased in type IIb
      fibers of either F or T muscles or both. Malate dehydrogenase was not changed in
      fibers of any type in either F or T muscle.

PMID- 1388151
TI  - Alpha 6.beta 1 integrin (laminin receptor) is down-regulated by tumor necrosis
      factor alpha and interleukin-1 beta in human endothelial cells.
AB  - Endothelial cells from human umbilical vein (HEC) express several distinct
      integrin complexes that mediate the interaction with the basal membrane
      components. In this paper we show that treatment with tumor necrosis factor alpha
      (TNF alpha) down-regulates the expression of the laminin receptor alpha 6.beta 1
      integrin in cultured HEC. After 48 h of treatment with TNF alpha, the level of
      expression of the alpha 6.beta 1 complex reached 20% of the control value. The
      down-regulation of the alpha 6.beta 1 integrin is caused by a decreased
      expression of the alpha 6 subunit, whereas the synthesis of the beta 1 subunit
      remains constant. Northern blot analysis shows that the decreased level of alpha
      6 subunit synthesis is caused by down-regulation of alpha 6 mRNA in TNF alpha
      treated HEC. TNF alpha treatment does not alter the expression of alpha 2, alpha
      3, and alpha 5 integrins, also present on endothelial cell surface, thus showing
      that this cytokine has a selective action on distinct integrin complexes. Down
      regulation of alpha 6.beta 1 correlates with pronounced reduction in adhesion of
      TNF alpha-treated HEC to laminin, but not to fibronectin-coated culture dishes.
      In addition to TNF alpha, interleukin-1 beta also decreases the expression of the
      alpha 6.beta 1 integrin and reduces adhesion to laminin, thus suggesting that
      this regulation plays an important role in inflammation.

PMID- 1388152
TI  - Allosteric modulation of Leishmania donovani plasma membrane Ca(2+)-ATPase by
      endogenous calmodulin.
AB  - The plasma membrane of the human pathogen Leishmania donovani possesses a high
      affinity transmembrane Ca(2+)-ATPase that has its catalytic site oriented toward
      the cytoplasmic milieu (Ghosh, J., Ray, M., Sarkar, S., and Bhaduri, A. (1990) J.
      Biol. Chem. 265, 11345-11351). When the enzyme is studied in its more authentic,
      physiologically relevant, membrane-associated form, it exhibits pronounced
      sigmoidal kinetics with Ca2+ (K0.5 approximately 700 nM) in a trans-1,2
      diaminocyclohexane-N,N,N',N'-tetraacetic acid buffering system that effectively
      complexes all available Mg2+. Addition of exogenous Mg2+ (60 microM) completely
      abolishes sigmoidicity and establishes strictly hyperbolic kinetics, and the Km
      for Ca2+ reduces to 100 nM. Mg2+ can be replaced by heterologous calmodulin. The
      exclusive dependence of the enzyme on only Ca2+ for its activity and its positive
      allosteric modulation by Mg2+ distinguish this enzyme from other well
      characterized plasma membrane Ca(2+)-ATPases. Employing this Ca(2+)-ATPase as the
      assay system, a soluble endogenous activating protein factor was purified that,
      by several criteria, corresponds to authentic calmodulin. The parasite calmodulin
      shifts the kinetics to hyperbolic kinetics, increases the Vmax 2-fold, and most
      important lowers the Km (approximately 100 nM) to a physiological level. The
      interaction with endogenous calmodulin thus converts the enzyme from a totally
      inactive to a fully active state.

PMID- 1388153
TI  - Action of neopullulanase. Neopullulanase catalyzes both hydrolysis and
      transglycosylation at alpha-(1----4)- and alpha-(1----6)-glucosidic linkages.
AB  - The transglycosylation reaction catalyzed by neopullulanase was analyzed.
      Radioactive oligosaccharides were produced when the enzyme acted on maltotriose
      in the presence of [U-14C]glucose. Some of the radioactive oligosaccharides had
      only alpha-(1----4)-glucosidic linkages, but others were suggested to have alpha
      (1----6)-glucosidic linkages. The existence of alpha-(1----6)-glucosidic linkages
      in the products from maltotriose with neopullulanase was proven by proton NMR
      spectroscopy and methylation analysis. We previously reported that the one active
      center of neopullulanase catalyzes the hydrolysis of alpha-(1----4)- and alpha-(1
      ---6)-glucosidic linkages (Kuriki, T., Takata, H., Okada, S., and Imanaka, T.
      (1991) J. Bacteriol. 173,6147-6152). These facts proved that neopullulanase
      catalyzed all four types of reactions: hydrolysis of alpha-(1----4)-glucosidic
      linkage, hydrolysis of alpha-(1----6)-glucosidic linkage, transglycosylation to
      form alpha-(1----4)-glucosidic linkage, and transglycosylation to form alpha-(1--
      -6)-glucosidic linkage. The four reactions are typically catalyzed by alpha
      amylase, pullulanase, cyclomaltodextrin glucanotransferase, and 1,4-alpha-D
      glucan branching enzyme, respectively. These four enzymes have some structural
      similarities to one other, but reactions catalyzed by the enzymes are considered
      to be distinctive: the four reactions are individually catalyzed by each of the
      enzymes. The experimental results obtained from the analysis of the reaction of
      the neopullulanase exhibited that the four reactions can be catalyzed in the same
      mechanism.

PMID- 1388154
TI  - The kinetics for the phosphoryl transfer steps of the sarcoplasmic reticulum
      calcium ATPase are the same with strontium and with calcium bound to the
      transport sites.
AB  - Rate constants for most of the steps of the reaction cycle of the sarcoplasmic
      reticulum calcium-ATPase are similar or identical with Ca2+ or Sr2+ as the
      transported ions in spite of the large differences in the size and affinity of
      Ca2+ and Sr2+ (5 mM MgCl2, 100 mM KCl, pH 7.0, 25 degrees C). Phosphorylation of
      cE.Sr2 and cE.Ca2 by ATP occurs with kp = 220-235 s-1, whereas phosphorylation of
      E.ATP+Ca2+ or Sr2+ is consistent with kb = 50-70 s-1. Hydrolysis of E
      approximately P.Sr2 and E approximately P.Ca2 occurs with kt = 20 s-1, and the
      addition of 7 mM ADP to E approximately P.Sr2 or to E approximately P.Ca2 gives a
      burst of approximately 43% dephosphorylation, followed by dephosphorylation with
      k = 46 s-1. However, one Sr2+ ion dissociates from cE.Sr2 and from cE.ATP.Sr2
      with k congruent to 120 s-1, whereas one Ca2+ ion dissociates from cE.Ca2 with k
      = 38 s-1 and from cE.ATP.Ca2 with k = 80 s-1.

PMID- 1388155
TI  - Binding of two Sr2+ ions changes the chemical specificities for phosphorylation
      of the sarcoplasmic reticulum calcium ATPase through a stepwise mechanism.
AB  - The sequential binding of Sr2+ and Ca2+ to the cytoplasmic transport sites of the
      sarcoplasmic reticulum calcium ATPase allows the formation of two different mixed
      complexes: cE.Sr.Ca, with Sr2+ bound to the "inner" site and Ca2+ bound to the
      "outer" site, and cE. Ca.Sr, with Ca2+ bound to the inner site and Sr2+ bound to
      the outer site (pH 7.0, 25 degrees C, 10 mM MgCl2, 100 mM KCl). Both cE.Sr.45Ca
      and cE.45Ca.Sr react with ATP to internalize one 45Ca/phosphoenzyme. The value of
      K0.5 = 83 microM Sr2+ for activation of the enzyme for phosphorylation by ATP is
      much larger than K0.5 = 28 microM Sr2+ for inhibition of phosphoenzyme formation
      from inorganic phosphate (eta H = 1.0-1.3). These results are consistent with the
      sequential binding of two strontium ions with negative cooperativity and
      dissociation constants of KSr1 = 35 microM and KSr2 = 55 microM. The species
      cE.Sr2 and cE.Ca2 react rapidly with ATP but not inorganic phosphate. However,
      enzyme with one strontium bound, cE.Sr, does not react with either inorganic
      phosphate or ATP. Therefore, the conformational changes in the enzyme that alter
      the chemical specificity for phosphorylation by ATP and by inorganic phosphate
      are different. This requires the existence of at least three forms of the
      unphosphorylated enzyme with three different chemical specificities for
      catalysis.

PMID- 1388156
TI  - Glycan components in the glycoinositol phospholipid anchor of human erythrocyte
      acetylcholinesterase. Novel fragments produced by trifluoroacetic acid.
AB  - Inositol glycans were prepared from reductively radiomethylated human erythrocyte
      acetylcholinesterase by sequential treatment with Proteinase K, methanolic KOH,
      and phosphatidylinositol-specific phospholipase C. Four glycans denoted alpha
      delta were resolved by anion exchange high performance liquid chromatography
      (HPLC). Each glycan was subjected to hydrolysis in 4 M trifluoroacetic acid, and
      their hexose and hexose phosphate compositions were determined by anion exchange
      HPLC. The predominant glycan alpha showed a relative stoichiometry of 2 mannoses,
      1 mannose 6-phosphate, 1 radiomethylated glucosamine, 1 radiomethylated
      ethanolamine, and 1 inositol. In contrast, the stoichiometry of glycan beta was 1
      mannose, 2 mannose 6-phosphates, 1 radiomethylated glucosamine, 2 radiomethylated
      ethanolamines, and 1 inositol. Glycans alpha and beta were analyzed by
      electrospray ionization-mass spectrometry, and respective parent ions of m/z 1266
      and 1417 were observed. The fragmentation pattern produced by collision-induced
      dissociation mass spectrometry of these parent ions was consistent with a common
      linear core glycan sequence prior to radiomethylation of ethanolamine-phosphate
      mannose - mannose - mannose - glucosamine - inositol. Glycan alpha contained a
      single additional radiomethylated phosphoethanolamine branching from the mannose
      adjacent to glucosamine, whereas glycan beta contained two additional
      radiomethylated phosphoethanolamines, one branching from each of the mannoses
      nearest to glucosamine. Trifluoroacetic acid hydrolysis did not cleave within the
      N,N-dimethylglucosamine-inositol-phosphate moiety in these glycans, and this
      component was resolved by anion exchange HPLC and structurally confirmed by mass
      spectrometry. Dephosphorylation of this component by treatment with 50% HF
      produced N,N-dimethylglucosamine-inositol, and this conjugate was shown to have a
      characteristic elution time on cation exchange chromatography in an amino acid
      analyzer. Both of these fragments involving an intact radiomethylated glucosamine
      inositol bond are proposed as new diagnostic indicators in the search for minor
      glycoinositol phospholipids in cells and tissues.

PMID- 1388157
TI  - Location of the two catalytic sites in intestinal lactase-phlorizin hydrolase.
      Comparison with sucrase-isomaltase and with other glycosidases, the membrane
      anchor of lactase-phlorizin hydrolase.
AB  - Lactase-phlorizin hydrolase was isolated by immunoadsorption chromatography from
      rabbit brush-border membrane vesicles. Inactivation of the enzyme with
      [3H]conduritol-B-epoxide, a covalent active site-directed inhibitor, labeled
      glutamates at positions 1271 and 1747. Glu1271 was assigned to lactase, Glu1747
      to phlorizin hydrolase activity. In contrast, the nucleophiles in the active
      sites of sucrase-isomaltase are aspartates (Asp505 and Asp1394). Asp505 is a part
      of the isomaltase active site and is localized on the larger subunit, which
      carries the membrane anchor also, while Asp1394 is a part of the active of
      sucrase. Alignment of these 2 nucleophilic Glu residues in lactase-phlorizin
      hydrolase and of their flanking regions with published sequences of several other
      beta-glycosidases allows the classification of the configuration retaining
      glycosidases into two major families: the "Asp" and the "Glu" glycosidases,
      depending on the carboxylate presumed to interact with the putative oxocarbonium
      ion in the transition state. We offer some predictions as to the Glu acting as
      the nucleophile in the active site of some glycosidases. By hydrophobic
      photolabeling, the membrane-spanning domain of lactase-phlorizin hydrolase was
      directly localized in the carboxyl-terminal region thus confirming this enzyme as
      a monotopic type I protein (i.e. with Nout-Cin orientation) of the brush-border
      membranes. A simplified version of the Me2+ precipitation method to efficiently
      and simply prepare brush-border membrane vesicles is also reported.

PMID- 1388158
TI  - Structure of the vacuolar ATPase from Neurospora crassa as determined by electron
      microscopy.
AB  - We have examined the structure of the vacuolar ATPase of Neurospora crassa using
      negatively stained preparations of vacuolar membranes and of detergent
      solubilized and gradient-purified ATPase complexes. We also examined the
      peripheral sector (V1) of the enzyme after it had been removed and purified.
      Using different stains, vacuolar membranes displayed ball-and-stalk structures
      similar to those of the intact mitochondrial ATPase. However, the vacuolar ATPase
      was clearly different from the mitochondrial ATPase in both size and structural
      features. The vacuolar enzyme had a much larger head domain with a distinct cleft
      down the middle of the complex. This domain was held above the membrane by a
      prominent stalk. Most intriguing was the presence of basal components. These
      structures appeared to project from the vacuolar membrane near the base of the
      stalks. Detergent-solubilized, gradient-purified ATPases displayed the same head,
      stalk, and basal features as those found with the intact enzyme on vacuolar
      membranes. The mitochondrial ATPase was significantly smaller, and no clefted
      head domains or basal components were observed. When V1 and F1 particles were
      directly compared, a significant difference in size and shape between these two
      soluble ATPase sectors was apparent. V1 retained all of the features seen in the
      globular head of the intact complex: V-shaped, triangular, and square forms
      around a stain-filled core.

PMID- 1388159
TI  - A novel ganglioside expressed by mouse hematopoietic cell lines.
AB  - Mouse progenitor T cell-derived cell lines were established by fusion of cells of
      hematopoietic organs such as bone marrow and fetal liver with T lymphoma (BW5147)
      to determine their characteristic cell-surface components. The hybridomas with
      the phenotype of Thy-1+, CD3-, CD4-, CD8- and expression of T cell receptor gene
      mRNA (BM216 and FL339) were selected for progenitor T cell-derived cell lines,
      and their ganglioside compositions were studied. A ganglioside component with a
      mobility slightly faster than that of bovine brain GD1a on high-performance thin
      layer chromatography was found in the cell extracts of these cell lines as one of
      the most abundant components and was absent in the extract of the parental cell
      line (BW5147). The structure of the ganglioside was determined to be: NeuAc alpha
      Gal beta-Gal beta-Gal alpha-Gal beta-Glc beta-ceramide. Gangliosides with such a
      sequence have never been found before, suggesting the possibility that the
      ganglioside is expressed as a surface marker of the cells in hematopoietic organs
      committed to a specific cell lineage, presumably to T cell lineage. cells in
      hematopoietic organs committed to a specific

PMID- 1388160
TI  - Determination of the 1-ethyl-3-[(3-dimethylamino)propyl]-carbodiimide- induced
      cross-link between the beta and epsilon subunits of Escherichia coli F1-ATPase.
AB  - The zero-length cross-link between the inhibitory epsilon subunit and one of
      three catalytic beta subunits of Escherichia coli F1-ATPase (alpha 3 beta 3 gamma
      delta epsilon), induced by a water-soluble carbodiimide, 1-ethyl-3-[(3
      dimethylamino) propyl]-carbodiimide (EDC), has been determined at the amino acid
      level. Lability of cross-linked beta-epsilon to base suggested an ester cross
      link rather than the expected amide. A 10-kDa cross-linked CNBr fragment derived
      from beta-epsilon was identified by electrophoresis on high percentage
      polyacrylamide gels. Sequence analysis of this peptide revealed the constituent
      peptides to be Asp-380 to Met-431 of beta and Glu-96 to Met-138 of epsilon. Glu
      381 of beta was absent from cycle 2 indicating that it was one of the cross
      linked residues, but no potential cross-linked residue in epsilon was identified
      in this analysis. A form of epsilon containing a methionine residue in place of
      Val-112 (epsilon V112M) was produced by site-directed mutagenesis. epsilon V112M
      was incorporated into F1-ATPase which was then cross-linked with EDC. An 8-kDa
      cross-linked CNBr fragment of beta-epsilon V112M was shown to contain the peptide
      of epsilon between residues Glu-96 and Met-112 and the peptide of beta between
      residues Asp-380 and Met-431. Again residue Glu-381 of beta was notably reduced
      and no missing residue from the epsilon peptide could be identified, but the
      peptide sequence limited the possible choices to Ser-106, Ser-107, or Ser-108.
      Furthermore, an epsilon mutant in which Ser-108 was replaced by cysteine could no
      longer be cross-linked to a beta subunit in F1-ATPase by EDC. Both mutant forms
      of epsilon supported growth of an uncC-deficient E. coli strain and inhibited F1
      ATPase. These results indicate that the EDC-induced cross-link between the beta
      and epsilon subunits of F1-ATPase is an ester linkage between beta-Glu-381 and,
      likely, epsilon-Ser-108. As these residues must be located immediately adjacent
      to one another in F1-ATPase, our results define a site of subunit-subunit contact
      between beta and epsilon.

PMID- 1388161
TI  - Ankyrin regulation: an alternatively spliced segment of the regulatory domain
      functions as an intramolecular modulator.
AB  - This study of two forms of ankyrin (protein 2.1 and 2.2) from human erythrocytes
      has revealed a role for alternate exon usage at the level of regulation of
      protein interactions. The smaller form of ankyrin (protein 2.2), which lacks a
      portion of the regulatory domain due to alternative splicing of pre-mRNA,
      exhibits increased affinity for the cytoplasmic domain of the anion exchanger,
      spectrin, and tubulin. Direct evidence that at least one of these associations is
      modulated by the alternatively spliced segment of the regulatory domain is
      provided by experiments utilizing a polypeptide that is comprised of residues
      1513-1674 corresponding to the portion of the regulatory domain missing from
      protein 2.2. Addition of this regulatory domain polypeptide to binding assays
      reversed the increase in affinity of protein 2.2 for the anion exchanger. The
      inhibitory activity of the regulatory domain polypeptide in these assays is
      accompanied by a direct interaction with a site that is available on the smaller
      form of ankyrin and is distinct from the binding site for the anion exchanger.
      These results support the idea that the alternatively spliced segment within the
      regulatory domain of erythrocyte ankyrin performs a repressor function and acts
      through an allosteric mechanism involving interaction(s) at a site separate from
      the binding site for the anion exchanger.

PMID- 1388162
TI  - Kinetic characterization of the substrate reaction between a complex of
      antithrombin with a synthetic reactive-bond loop tetradecapeptide and four target
      proteinases of the inhibitor.
AB  - A tetradecapeptide corresponding to the P1 to P14 region of the reactive-bond
      loop of antithrombin (AT) binds to the inhibitor, presumably as a middle strand
      of the A beta-sheet, thereby converting AT from an inhibitor to a substrate of
      thrombin (Bjork, I., Ylinenjarvi, K., Olson, S.T., and Bock, P. E. (1992) J.
      Biol. Chem. 267, 1976-1982). The kinetics of cleavage of the AT reactive bond in
      the AT-peptide complex by four target proteinases were quantified by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and densitometry. The kcat/Km
      values for thrombin and factor IXa were indistinguishable from the second-order
      rate constants for AT inhibition of these enzymes, whereas the values for factor
      Xa and plasmin were 10-17-fold higher than the inhibition rate constants. Heparin
      with high affinity for AT accelerated the substrate reaction with thrombin to an
      extent consistent with the reduced heparin affinity of the AT-peptide complex.
      These data show that blocking by the peptide of the putative intramolecular
      association of the P1 to P14 region of the AT reactive-bond loop with the A beta
      sheet leads to AT functioning as a substrate of its target enzymes with an
      efficiency that equals or exceeds the action of uncomplexed AT as an inhibitor
      and with the expected heparin activation. The results thus suggest that a
      substrate-like attack of the proteinase on the inhibitor reactive bond in an
      exposed loop initiates the inhibition reaction. This attack presumably induces
      the subsequent trapping of the enzyme by the insertion of the reactive-bond loop
      into the A beta-sheet.

PMID- 1388163
TI  - Effects of decreased cytosine content on rho interaction with the rho-dependent
      terminator trp t' in Escherichia coli.
AB  - We have introduced multiple cytosine-to-uracil mutations in the rho-dependent
      transcription terminator trp t' and have characterized a subset of the resulting
      mutant derivatives in vitro for termination efficiency, affinity for rho, and
      stimulation of rho-ATPase activity. No specific cytosine residue appears to be
      required for termination, and at least 13 of the 28 cytosine residues in the 104
      nucleotide trp t' region can be mutated with little effect on termination
      efficiency. One derivative with 11 mutations is significantly less efficient than
      other derivatives with a similar number of mutations, implying that the pattern
      of alterations, as well as the number, can affect termination efficiency.
      Derivatives with 20 and 28 cytosines mutated are non-functional in termination,
      consistent with the idea that cytosines are required for rho-dependent
      termination. Our results are inconsistent, however, with the hypothesis that the
      termination efficiency is directly related to the cytosine/guanine ratio in the
      nascent transcript. The results support the idea that neither RNA binding
      affinity nor ATPase activation per se are accurate predictors of rho-dependent
      termination efficiency.

PMID- 1388164
TI  - Pyruvic acid is attached through its central carbon atom to the amino terminus of
      the recombinant DNA-derived DNA-binding protein Ner of bacteriophage Mu.
AB  - Ner protein of bacteriophage Mu, produced by recombinant DNA techniques in
      Escherichia coli, has been found to possess a molecule of pyruvic acid attached
      covalently through carbon-2 to the amino-terminal cysteine residue. The intact
      protein and the amino-terminal chymotryptic peptide were found by mass
      spectrometry to be 70 mass units heavier than expected. The modified peptide was
      unstable under mildly acid or mildly basic conditions. Two-dimensional nuclear
      magnetic resonance spectroscopy of the modified and unmodified forms of the amino
      terminal chymotryptic peptide was consistent with the presence of pyruvate linked
      through carbon-2 to the amino-terminal Cys residue. Treatment of the modified
      form with 2,4-dinitrophenylhydrazine in acid medium led to the expected hydrazone
      of pyruvic acid, which was identified by high pressure liquid chromatography. Of
      the two proteins known to be modified by pyruvate through its central carbon (the
      other being human adult hemoglobin, in which the modified form represents only a
      very minor fraction), Ner is the first protein found to be modified
      quantitatively. Given the instability of the modification, it may be more
      prevalent than recognized hitherto. Incubation with 2,4-dinitrophenylhydrazine
      may offer a useful means of detecting the presence of pyruvate linked to proteins
      in this way.

PMID- 1388165
TI  - Identification and characterization of columbid annexin Icp37. Insights into the
      evolution of annexin I phosphorylation sites.
AB  - Annexin I (AnxI) contains phosphorylation sites in its "hinge region" that have
      been implicated in the regulation of cell growth and/or differentiation. A pigeon
      (Columba livia) isoform of this protein, annexin Icp35 (cp35), has a very similar
      amino acid sequence overall but an unrelated sequence that lacks phosphorylation
      sites in the hinge region. We now report the identification and characterization
      of annexin Icp37 (cp37) from pigeon. Genomic cloning and Southern blot analysis
      demonstrated that cp37 and cp35 were encoded by separated genes. Prolactin
      induced the expression of cp35 mRNA but not cp37. The amino acid sequence of cp37
      was deduced from a cDNA clone and found to share 93 and 75% sequence identity
      with cp35 and human AnxI, respectively. The amino acid sequence of cp37 bore
      similarities to both AnxI and cp35 in the critical hinge region. Like AnxI, cp37
      contained consensus phosphorylation sites in its amino acid sequence and was
      phosphorylated on tyrosine by the EGF receptor/kinase and on serine by protein
      kinase C in vitro. Despite the functional similarities between cp37 and AnxI, the
      nucleotide sequence that encoded the hinge region of cp37 was very similar to the
      analogous region of cp35, but different from that of AnxI. We propose that
      certain features shared by cp37 and AnxI are the products of convergent
      evolution. The fact that evolution independently selected for two annexin I-like
      genes (cp37 and anxI) encoding analogous phosphorylation sites is strong evidence
      that phosphorylation is important for the regulation of the biological activity
      of these proteins.

PMID- 1388166
TI  - The asparagine-linked oligosaccharides on tissue factor pathway inhibitor
      terminate with SO4-4GalNAc beta 1, 4GlcNAc beta 1,2 Mana alpha.
AB  - Tissue factor pathway inhibitor (TFPI) produced by endothelial cells contains
      sulfated Asn-linked oligosaccharides. We have determined that greater than 70% of
      the oligosaccharides on recombinant TFPI expressed in 293 cells terminate with
      the sequence SO4-4GalNAc beta 1, 4GlcNAc beta 1, 2Man alpha. Oligosaccharides
      terminating with this sequence have previously been described on lutropin,
      thyrotropin, and pro-opiomelanocortin: glycoproteins synthesized in the anterior
      pituitary. A GalNAc-transferase that recognizes the tripeptide motif Pro-Xaa
      Arg/Lys 6-9 residues N-terminal to Asn glycosylation sites accounts for the
      specific addition of GalNAc to the oligosaccharide acceptor on these
      glycoproteins, whereas a GalNAc beta 1,4GlcNAc beta 1, 2Man alpha-4
      sulfotransferase accounts for the addition of sulfate. The sulfated
      oligosaccharides present on these hormones are responsible for their rapid
      clearance from plasma by a receptor in hepatic reticuloendothelial cells. GalNAc-
      and sulfotransferase activities with the same properties as those expressed in
      the pituitary are detected at high levels in 293 cells and at lower levels in
      endothelial cells. Chinese hamster ovary (CHO) cells do not contain detectable
      levels of either transferase and rTFPI expressed in CHO cells does not contain
      sulfated Asn-linked oligosaccharides. TFPI contains the sequence Pro-Phe-Lys, 9
      residues N-terminal to the glycosylation site at position 228; this tripeptide
      may act as the recognition sequence for the GalNAc-transferase. rTFPI produced by
      293 cells, but not that produced by CHO cells, is bound by the receptor on
      hepatic reticuloendothelial cells suggesting the sulfated structures play a role
      in the biologic behavior of TFPI.

PMID- 1388167
TI  - Mutagenesis of the C-terminal nucleotide-binding site of an anion-translocating
      ATPase.
AB  - An oxyanion-translocating ATPase encoded by a bacterial plasmid confers
      resistance to antiomonials and arsenicals in Escherichia coli by extrusion of the
      toxic oxyanions from the cytosol. The anion pump is composed of two polypeptides,
      the ArsA and ArsB proteins. Purified ArsA protein is an oxyanion-stimulated
      ATPase with two nucleotide-binding consensus sequences, one in the N-terminal
      half and one in the C-terminal half of the protein. The ArsA protein can be
      labeled with [alpha-32P]ATP by a UV-catalyzed reaction. Previously reported
      mutations in the N-terminal site abolish photoadduct formation. Using site
      directed mutagenesis the glycine-rich region of the C-terminal putative
      nucleotide-binding sequence was altered. Three C-terminal site mutant proteins
      (GR337, KE340, KN340) were analyzed, as well as one additional N-terminal mutant
      protein (KE21). Strains bearing the mutated plasmids were arsenite sensitive to
      varying degrees. The purified ArsA protein from mutant KE340 retained
      approximately 20% of the wild type oxyanion-stimulated ATPase activity, while the
      purified proteins from the other mutants were catalytically inactive. The KE21
      mutation in the N-terminal nucleotide-binding site eliminated photoadduct
      formation with [alpha-32P] ATP, while the purified proteins with mutations in the
      C-terminal site retained the ability to form a photoadduct. Each mutant protein
      was capable of forming a membrane-bound complex in arsB expressing strains. These
      results suggest first that both sites are required for resistance and ATPase
      activity, and second that the conserved lysyl residue in the glycine-rich loop of
      the C-terminal nucleotide-binding site is not essential for catalytic activity.

PMID- 1388168
TI  - Plasmin and the regulation of tissue-type plasminogen activator biosynthesis in
      human endothelial cells.
AB  - Plasmin inhibited the biosynthesis of tissue-type plasminogen activator (tPA)
      antigen by human umbilical vein endothelial cells (HUVEC) in a dose-dependent
      manner. The amount of tPA antigen found in the 24-h conditioned medium of cells
      treated with 100 nM plasmin for 1 h was 20-30% of that in the control group.
      However, in contrast to tPA, such treatment led to a 3-fold increase in
      plasminogen activator inhibitor (PAI) activity, whereas the amount of PAI type 1
      antigen was unchanged. The effects of plasmin on HUVEC were binding- and
      catalytic activity-dependent and were specifically blocked by epsilon
      aminocaproic acid. Microplasmin, which has no kringle domains, was less effective
      in reducing tPA antigen biosynthesis or enhancing PAI activity in HUVEC. Kringle
      domains of plasmin affected neither tPA antigen nor PAI activity of the cells.
      Other proteases including chymotrypsin, trypsin, and collagenase at comparable
      concentrations did not have a significant effect on the biosynthesis of tPA
      antigen or PAI activity of HUVEC. Thrombin stimulated the biosynthesis of tPA and
      PAI-1 antigens by HUVEC. Thrombin also stimulated an increase in the protein
      kinase activity in HUVEC, whereas plasmin inhibited the protein kinase activity
      of the cells. It is possible that plasmin regulates the biosynthesis of tPA in
      HUVEC through the signal transduction pathway involving protein kinase.

PMID- 1388169
TI  - Functional consequences of alterations to Glu309, Glu771, and Asp800 in the
      Ca(2+)-ATPase of sarcoplasmic reticulum.
AB  - Site-specific mutagenesis was used to replace Glu309, Glu771, and Asp800 in the
      Ca(2+)-ATPase of rabbit fast twitch muscle sarcoplasmic reticulum with their
      corresponding amides. These residues are predicted to lie in the transmembrane
      domain and have been suggested as oxygen ligands for Ca2+ binding at high
      affinity sites (Clarke, D. M., Loo, T. W., Inesi, G., and MacLennan, D. H. (1989)
      Nature 339, 476-478). The Glu309----Gln and Asp800----Asn mutants were unable to
      form a phosphoenzyme from ATP at the Ca2+ concentrations examined (up to 12.5
      mM), whereas the Glu771----Gln mutant phosphorylated from ATP at 2.5 mM Ca2+. In
      all three mutants, Ca2+ at concentrations well below 12.5 mM prevented or
      inhibited phosphorylation with Pi, suggesting that at least one calcium-binding
      site was functioning in each mutant. In the mutants Glu309----Gln and Glu771---
      Gln, the ADP-insensitive phosphoenzyme intermediate was unusually stable, as
      indicated by a very low rate of dephosphorylation observed in kinetic experiments
      and by an increased apparent affinity for Pi determined in equilibrium
      phosphorylation experiments. These data indicate a central role of Glu309 and
      Glu771 in the energy-transducing conformational changes and/or in the activation
      of phosphoenzyme hydrolysis.

PMID- 1388170
TI  - Host factor requirements for processive antitermination of transcription and
      suppression of pausing by the N protein of bacteriophage lambda.
AB  - The N protein of phage lambda prevents termination of transcription by
      Escherichia coli RNA polymerase at Rho-dependent and -independent terminators in
      the lambda early operons. The modification of RNA polymerase by N requires an N
      utilization (nut) site, present in each lambda early operon, and involves the E.
      coli factors NusA, NusB, NusG, and ribosomal protein S10. We show that, in the
      presence of NusA, N inhibits pausing by RNA polymerase and Rho-dependent
      termination in vitro at three sites in the lambda terminator tR1 which are
      located less than 100 base pairs downstream from nutR. NusA is also sufficient
      for partial antitermination at sites located farther downstream from nutL and
      nutR if there is a high concentration of N in the reaction. At low concentrations
      of N, the additional factors NusB, S10, and NusG are essential for
      antitermination at distal sites. In these conditions, the presence of NusA, NusB,
      S10, and NusG in the reaction enables N-modified RNA polymerase to elongate
      efficiently and processively through Rho-dependent and -independent terminators
      over distances as great as 7 kilobases downstream from the lambda nut sites. This
      substantial processivity of antitermination in vitro also occurs in vivo and
      probably reflects the stable association of N, NusA, NusB, S10, and NusG with RNA
      polymerase and nut site RNA in elongation complexes transcribing the lambda
      chromosome.

PMID- 1388171
TI  - Structure of the rat plasma membrane Ca(2+)-ATPase isoform 3 gene and
      characterization of alternative splicing and transcription products. Skeletal
      muscle-specific splicing results in a plasma membrane Ca(2+)-ATPase with a novel
      calmodulin-binding domain.
AB  - We have isolated the rat gene encoding isoform 3 of the plasma membrane Ca(2+)
      ATPase (PMCA3) and have determined its exon/intron organization. The PMCA3 gene
      contains 24 exons and spans approximately 70 kilobases. In addition, we have
      analyzed the splicing and polyadenylation patterns leading to the production of
      an alternative 4.5-kilobase (PMCA3) skeletal muscle mRNA that differs from the
      previously characterized 7.5-kilobase brain mRNA (Greeb, J., and Shull, G. E.
      (1989) J. Biol. Chem. 264, 18569-18576). cDNA cloning, Northern blot
      hybridization, and polymerase chain reaction analyses of the 4.5-kilobase mRNA
      demonstrate (i) the inclusion of a novel 68-nucleotide exon (exon 22) that is
      specific for skeletal muscle and significantly alters the calmodulin-binding
      domain and (ii) the utilization of an alternative polyadenylation site following
      exon 23 which eliminates the last coding exon (exon 24) and 3'-untranslated
      sequence of the 7.5-kilobase mRNA. We have also identified a 42-nucleotide exon
      (exon 8) that is included in the skeletal muscle PMCA3 mRNAs, but may be either
      included or excluded in the brain mRNAs. Exon 8 is inserted immediately before
      the sequence encoding a putative phospholipid binding domain and thus may alter
      regulatory interactions of the enzyme with acidic phospholipids.

PMID- 1388172
TI  - Lack of scientific evidence for the treatment of lateral epicondylitis of the
      elbow. An attempted meta-analysis.
AB  - We have reviewed 185 articles published since 1966 to assess the scientific
      evidence for methods of treatment for lateral epicondylitis of the elbow. Of the
      185 articles, 78 discussed treatment, but since the natural history of the
      syndrome is uncertain we considered only those series with concurrent control
      groups. Only 18 of these were randomised and controlled studies. We then graded
      these papers for scientific validity, using the methods of Chalmers et al (1981).
      The mean score of the 18 articles was only 33%, with a range from 6% to 73%. A
      minimum of 70% is required for a valid clinical trial, and we therefore concluded
      that there was insufficient scientific evidence to support any of the current
      methods of treatment. There were too many methodological differences to allow a
      quantitative meta-analysis, but our qualitative review established the importance
      of the natural evolution of the syndrome and of the placebo effect of all
      treatments. Properly designed, controlled trials are needed.

PMID- 1388173
TI  - Annular tears and disc degeneration in the lumbar spine. A post-mortem study of
      135 discs.
AB  - We studied 135 lumbar discs from 27 spines removed post-mortem from subjects of
      an average age of 31.5 years. Defects of the annulus fibrosus were classified as
      peripheral, circumferential or radiating; the nucleus pulposus as normal,
      moderately or severely degenerate. Peripheral tears were more frequent in the
      anterior annulus, except in the L5-S1 disc. Circumferential tears were equally
      distributed between the anterior and the posterior annulus. Almost all the
      radiating tears were in the posterior annulus, and closely related to the
      presence of severe nuclear degeneration. Histology suggested that peripheral
      tears were due to trauma rather than biochemical degradation, and that they
      developed independently of nuclear degeneration. The association of peripheral
      annular lesions with low back pain is uncertain but our study suggests that they
      may have a role in the pathogenesis of discogenic pain.

PMID- 1388174
TI  - Albumin impregnated vascular grafts: albumin resorption and tissue reactions.
AB  - This study aimed to determine the kinetics of albumin resorption from and the
      healing of two types of albumin impregnated Vasculour II (Bard Cardiovascular)
      Dacron grafts (ACG-A and ACG-B) using whole blood preclotted Vasculour II Dacron
      grafts (without albumin) as controls (PCC). Prostheses measuring 4 mm ID x 50 mm
      length were implanted in the aortoiliac position in 24 dogs (ACG-A n = 12, ACG-B
      n = 24, PCC n = 12) and explanted after 1, 2 4, and 6 months. Platelet count,
      platelet aggregometry to 10(-5) M ADP, prothrombin time (PT), and partial
      thromboplastin time (PTT) were determined preoperatively and at explantation.
      Sections of the explanted grafts were assayed for human albumin by
      immunohistochemical techniques utilizing a rabbit polyclonal mono-specific
      antibody for human albumin followed by the addition of a biotinylated goat anti
      rabbit IgG. Immunoperoxidase staining was then performed using Avidin D horse
      radish peroxidase. Histology of the grafts (light microscopy, scanning electron
      microscopy, and transmission electron microscopy) as well as percent thrombus
      free surface area (TFSA) by computerized planimetry were also determined. Seven
      of 48 grafts were occluded (85.4% patency) with no difference among the three
      groups. Platelet aggregometry was not predictive of graft patency. No change in
      PT or PTT occurred nor was there any difference among the three groups. Retained
      albumin was detected in every one-month explant but not beyond that time, with
      the sensitivity for detecting human albumin in this assay being 20 mg albumin per
      gram of Dacron. All ACG explants at one month revealed inner capsular fibrin
      coagula not present in PCC specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388175
TI  - The influence of competitive flow on graft patency.
AB  - To evaluate the effects of competitive flow, bilateral aorto-iliac ePTFE grafts,
      10 cm in length and with an internal diameter of 6 mm, were placed in ten mongrel
      dogs. On one side the external iliac artery was ligated (the control side); on
      the opposite side (the experimental side) flow continued through the native aorto
      iliac system, as well as the graft, to allow a situation of competitive flow.
      Flow measurements showed the experimental graft carried 38.6% of the total blood
      flow going to the ipsilateral external iliac artery. After 30 days the grafts
      were exposed and patency and flow were evaluated by Doppler ultrasound. The
      control side showed 60% patency; all of the grafts on the experimental side were
      occluded. In addition, complete endothelial healing was observed at the occluded
      ostia of all experimental grafts. We conclude that competitive flow does
      influence graft patency and that graft thrombosis appears to be a relatively
      early phenomenon, as evidenced by the endothelial healing which occurred.

PMID- 1388176
TI  - Apical endosomes isolated from kidney collecting duct principal cells lack
      subunits of the proton pumping ATPase.
AB  - Endocytic vesicles that are involved in the vasopressin-stimulated recycling of
      water channels to and from the apical membrane of kidney collecting duct
      principal cells were isolated from rat renal papilla by differential and Percoll
      density gradient centrifugation. Fluorescence quenching measurements showed that
      the isolated vesicles maintained a high, HgCl2-sensitive water permeability,
      consistent with the presence of vasopressin-sensitive water channels. They did
      not, however, exhibit ATP-dependent luminal acidification, nor any N
      ethylmaleimide-sensitive ATPase activity, properties that are characteristic of
      most acidic endosomal compartments. Western blotting with specific antibodies
      showed that the 31- and 70-kD cytoplasmically oriented subunits of the vacuolar
      proton pump were not detectable in these apical endosomes from the papilla,
      whereas they were present in endosomes prepared in parallel from the cortex. In
      contrast, the 56-kD subunit of the proton pump was abundant in papillary
      endosomes, and was localized at the apical pole of principal cells by
      immunocytochemistry. Finally, an antibody that recognizes the 16-kD transmembrane
      subunit of oat tonoplast ATPase cross-reacted with a distinct 16-kD band in
      cortical endosomes, but no 16-kD band was detectable in endosomes from the
      papilla. This antibody also recognized a 16-kD band in affinity-purified H+
      ATPase preparations from bovine kidney medulla. Therefore, early endosomes
      derived from the apical plasma membrane of collecting duct principal cells fail
      to acidify because they lack functionally important subunits of a vacuolar-type
      proton pumping ATPase, including the 16-kD transmembrane domain that serves as
      the proton-conducting channel, and the 70-kD cytoplasmic subunit that contains
      the ATPase catalytic site. This specialized, non-acidic early endosomal
      compartment appears to be involved primarily in the hormonally induced recycling
      of water channels to and from the apical plasma membrane of vasopressin-sensitive
      cells in the kidney collecting duct.

PMID- 1388177
TI  - Tripeptide RGD-dependent adhesion of articular chondrocytes to synovial
      fibroblasts.
AB  - Cell-cell interactions play an important role in the development of cartilage.
      Heterologous and homologous cell-cell interactions are critical for chondrogenic
      differentiation during development. Cell-cell interactions in the formation of
      fracture callus and cartilage neoplasia also invoke the process of cartilage
      differentiation. We have investigated cell-cell interactions between articular
      chondrocytes and synovial fibroblasts and show that there was enhanced binding
      between these two cell types compared to background binding of the labelled cells
      to the tissue culture plastic surface. The binding of chondrocytes to fibroblasts
      was temperature- and calcium-dependent, suggesting ligand-integrin involvement.
      The peptide, GRGDSP, which competes with the ligand-integrin through the
      tripeptide RGD (arginine-glycine-aspartic acid), almost completely inhibited
      chondrocyte attachment to synovial fibroblasts. The control peptide, GRGESP, had
      no inhibitory effect on binding. Antibodies to fibronectin (Fn) inhibited
      chondrocyte attachment by about 50%. Monoclonal antibodies to the alpha and beta
      chains of the fibronectin receptor (FnR) interfered with the attachment of
      chondrocytes to synovial fibroblasts. A combination of antibodies to Fn and to
      FnR did not completely abrogate chondrocyte binding, suggesting that other ligand
      receptors were involved in the adhesion process. Chondrocytes and fibroblasts
      were shown to express membrane-associated Fn and FnR, by immunofluorescence. The
      alpha and beta chains of FnR, migrating at 110 and 140 kDa, respectively, could
      be immunoprecipitated from [35S]methionine-labelled synovial fibroblasts and
      chondrocytes. Northern blots showed the presence of mRNA for the alpha and beta
      chains of fibronectin receptors in fibroblasts and chondrocytes. Changes in cell
      shape were observed in chondrocytes on attachment to fibroblasts, i.e. the
      chondrocytes appeared fibroblast-like, suggesting that the chondrocytes had
      dedifferentiated. These studies suggest that chondrocytes specifically bind to
      synovial fibroblasts through RGD-dependent receptors. beta 1 Integrins are
      involved in this adhesion process and these heterlogous cell interactions appear
      to have a negative influence on chondrogenic differentiation.

PMID- 1388178
TI  - Lymphocyte adhesion to high endothelium is mediated by two beta 1 integrin
      receptors for fibronectin, alpha 4 beta 1 and alpha 5 beta 1.
AB  - Using a rat model we have previously proposed a role for fibronectin as an
      adhesive ligand on high endothelial cells (HEC) for recirculating lymphocytes.
      Lymphocyte adhesion to high endothelial cells was blocked by CS1 peptide (from
      the type III connecting segment of fibronectin) and RGD-containing peptides using
      two different in vitro assays of lymphocyte-HEC recognition, the frozen section
      assay and cultured HEC. In order to study the receptors utilised by lymphocytes
      to bind to HEC we have developed a xenogeneic model in which the adhesion of
      human lymphocytes to HEC cultured from rat lymph nodes is measured. The basic
      properties of lymphocyte-HEC interaction were retained using human lymphocytes.
      CS1 peptide and RGD-containing peptides gave similar profiles of inhibition of
      lymphocyte adhesion as found previously using rat cells. FACS analysis showed
      that the majority of peripheral blood lymphocytes expressed two beta 1 integrin
      receptors, alpha 4 beta 1 and alpha 5 beta 1, which are known to recognise
      distinct adhesion domains in fibronectin. A subpopulation of lymphocytes also
      expressed alpha 3 beta 1, which, like alpha 5 beta 1, has been reported to be an
      RGD-dependent adhesion receptor for the central cell binding domain of
      fibronectin. Anti-alpha 4 and anti-alpha 5 subunit monoclonal antibodies
      maximally inhibited adhesion to HEC by 60% and 65%, respectively. Monoclonal
      antibodies to the common beta 1 subunit gave slightly higher inhibition at 70%.
      These results suggest that lymphocytes employ one or both of two different beta 1
      integrin fibronectin receptors to bind to HEC. The simultaneous or alternate
      engagement of two fibronectin receptors on the lymphocyte surface by immobilised
      fibronectin in the endothelial layer may contribute to the stabilisation of
      adhesive contacts or to the subsequent transendothelial migration of lymphocytes.
      In contrast to lymphocytes, peripheral blood neutrophils did not express any
      members of the beta 1 integrin family. The selective expression of beta 1
      integrins by lymphocytes and not neutrophils contrasted with the widespread
      distribution of the other homing-associated adhesion molecules, LECAM-1, CD44 and
      LFA-1, on these two cell types. It is thus possible that the selective expression
      of beta 1 integrins regulates the constitutive migration of lymphocytes but not
      neutrophils into organised lymphoid tissues.

PMID- 1388179
TI  - Akathisia-like motor restlessness in major depression responding to serotonin
      reuptake inhibition.

PMID- 1388180
TI  - Blood pressure reduction and recovery of stunned myocardium in the hypertrophied
      hypertensive heart.

PMID- 1388182
TI  - Hemodynamic and volume correlates of left ventricular diastolic relaxation and
      filling in patients with aortic stenosis.
AB  - OBJECTIVE: The aim of the present study was to evaluate the hemodynamic and
      volume correlates of early diastolic filling and isovolumetric relaxation in
      patients with aortic stenosis. BACKGROUND: Left ventricular diastolic relaxation
      and filling have been found to be heterogeneous in patients with aortic stenosis.
      Potential mechanisms underlying this heterogeneity include individual differences
      in the severity of muscle hypertrophy or systolic dysfunction, or both, in the
      presence and severity of mitral regurgitation and in the level of left atrial
      pressure. METHODS: Right (fluid-filled) and left (high fidelity micromanometer)
      ventricular pressures, left ventricular volumes (contrast angiography) and
      transmitral inflow dynamics (Doppler echocardiography) were measured in 17
      patients with isolated severe aortic stenosis (valve area less than 0.75 cm2).
      Measurements included left ventricular end-diastolic and end-systolic volumes,
      left ventricular ejection fraction, peak positive and negative first derivative
      of left ventricular pressure (dP/dt), the time constant of isovolumetric
      relaxation (tau), left ventricular end-diastolic pressure, left ventricular mass,
      left ventricular end-systolic stress, mean capillary wedge pressure and peak
      early (E) and late (A) transmitral filling velocities. Patients were
      subclassified according to left ventricular ejection performance at rest and mean
      capillary wedge pressure. RESULTS: Patients with normal ejection performance and
      normal mean capillary wedge pressure had a normal rate of isovolumetric left
      ventricular pressure decay and an abnormal diastolic filling pattern, with
      diastolic filling occurring primarily during atrial systole. In contrast, in
      patients with systolic dysfunction and elevated mean capillary wedge pressure,
      isovolumetric pressure decay was prolonged and diastolic filling occurred
      essentially during the rapid filling period, with reduced atrial contribution to
      left ventricular filling and a short isovolumetric relaxation period. Stepwise
      multiple linear regression analysis identified two variables as independent
      predictors of transmitral velocity profile and three variables independently
      predictive of the rate of left ventricular pressure decay. The single most
      important predictor of transmitral filling pattern was the pulmonary capillary
      wedge pressure (p less than 0.0001), followed by the left ventricular peak
      negative dP/dt (p = 0.002). The single most powerful predictor of the rate of
      reduction in left ventricular pressure was left ventricular mass index (p less
      than 0.0001), followed by end-systolic volume index (p = 0.0002) and left
      ventricular peak negative dP/dt (p = 0.0029). CONCLUSIONS: In patients with
      aortic stenosis, left ventricular filling is essentially determined by left
      atrial pressure, whereas isovolumetric relaxation more closely depends on the
      severity of muscle hypertrophy and chamber dilation.

PMID- 1388181
TI  - Therapeutic dissection after successful coronary balloon angioplasty: no
      influence on restenosis or on clinical outcome in 693 patients. The MERCATOR
      Study Group (Multicenter European Research Trial with Cilazapril after
      Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis).
AB  - OBJECTIVES: The objective of this study was to examine the relation between an
      angiographically visible coronary dissection immediately after successful
      coronary balloon angioplasty and a subsequent restenosis and long-term clinical
      outcome. BACKGROUND: The study population comprised all 693 patients who
      participated in the MERCATOR trial (randomized, double-blind, placebo-controlled
      restenosis prevention trial of cilazapril, 5 mg two times a day). METHODS:
      Cineangiographic films were processed and analyzed at a central angiographic core
      laboratory, without knowledge of clinical data, with use of an automated
      interpolated edge detection technique. Dissection was judged according to the
      National Heart, Lung, and Blood Institute classification. Angiographic follow-up
      was obtained in 94% of patients with 778 lesions. Two approaches were used to
      assess the restenosis phenomenon: 1) categoric, using the traditional cutoff
      criterion of greater than 50% diameter stenosis at follow-up, and 2) continuous,
      defined as absolute change in minimal lumen diameter (mm) between the
      postcoronary angioplasty and follow-up, adjusted for the vessel size (relative
      loss). Clinical outcome was ranked according to the most serious adverse clinical
      event per patient during the 6-month follow-up period, ranging from death,
      nonfatal myocardial infarction, coronary revascularization and recurrent angina
      requiring medical therapy to none of these. RESULTS: Dissection was present in
      247 (32%) of the 778 dilated lesions. The restenosis rate was 29% in lesions with
      and 30% in lesions without dissection (relative risk 0.97; 95% confidence
      interval 0.77 to 1.23). The relative loss in both groups was 0.10 (mean
      difference 0; 95% confidence interval -0.03 to 0.03). Clinical outcome ranged
      from death in 4 patients (0.9%) without dissection and 1 patient (0.4%) with
      dissection; nonfatal myocardial infarction in 4 (0.9%) without and 8 (3.2%) with
      dissection; coronary revascularization in 73 (16.6%) without and 32 (12.7%) with
      dissection; recurrent angina requiring medical therapy in 88 (20%) without and 47
      (18.7%) with dissection to no serious adverse event in 272 (61.7%) without and
      114 (65.1%) with dissection. CONCLUSIONS: These data indicate that a successfully
      dilated coronary lesion with an angiographically visible dissection is no more
      likely to develop restenosis, and is not associated with a worse clinical
      outcome, at 6-month follow-up than is a dilated lesion without visible dissection
      on the post-balloon angioplasty angiogram.

PMID- 1388183
TI  - Left ventricular volume determined echocardiographically by assuming a constant
      left ventricular epicardial long-axis/short-axis dimension ratio throughout the
      cardiac cycle.
AB  - OBJECTIVES: The purpose of this study was to develop and test a simplified
      echocardiographic method to calculate left ventricular volume. BACKGROUND: This
      method was based on the assumption that the ratio of the left ventricular
      epicardial long-axis dimension to the epicardial short-axis dimension was
      constant throughout the cardiac cycle. With use of this constant ratio, the
      method developed to calculate left ventricular volume at a given point in the
      cardiac cycle required the left ventricular endocardial long-axis dimension to be
      measured at only one point in the cardiac cycle. METHODS: Studies were performed
      in 13 normal dogs, 8 normal puppies, 9 normal pigs, 12 dogs with aortic stenosis,
      13 dogs with acute mitral regurgitation, 12 dogs with chronic mitral
      regurgitation, 7 dogs that had undergone mitral valve replacement and 6 pigs that
      had had chronic supraventricular tachycardia. Animals with aortic stenosis
      developed left ventricular pressure overload hypertrophy with a 60% increase in
      left ventricular mass; chronic mitral regurgitation caused left ventricular
      volume overload hypertrophy with a 46% increase in left ventricular volume;
      supraventricular tachycardia caused a dilated cardiomyopathy with a 55% decrease
      in left ventricular ejection fraction. RESULTS: The left ventricular epicardial
      long-axis/short-axis dimension ratio remained constant throughout the cardiac
      cycle in each animal group. End-diastolic and end-systolic volumes calculated
      with the simplified echocardiographic method correlated closely with
      angiographically measured volumes; for end-diastolic volume, echocardiographic
      end-diastolic volume = 1.0 (angiographic end-diastolic volume) -1.8 ml, r = 0.96;
      for end-systolic volume, echocardiographic end-systolic volume = 0.98
      (angiographic end-systolic volume) -0.7 ml, r = 0.95. CONCLUSIONS: Thus the left
      ventricular epicardial long-axis/short-axis dimension ratio was constant
      throughout the cardiac cycle in a variety of animal species and age groups and in
      the presence of cardiac diseases that significantly altered left ventricular
      geometry and function. The simplified echocardiographic method examined provided
      an accurate determination of left ventricular volumes.

PMID- 1388184
TI  - Segmental systolic responses to brief ischemia and reperfusion in the
      hypertrophied canine left ventricle.
AB  - OBJECTIVES AND BACKGROUND: Left ventricular hypertrophy is associated with
      increased mortality, increased myocardial infarct size and an increased incidence
      of sudden death. Although reperfusion after ischemia has been shown to result in
      decreased infarct size and recovery of systolic thickening, it is unknown how
      left ventricular hypertrophy might influence recovery of regional systolic
      thickening after ischemia and reperfusion. We hypothesized that left ventricular
      hypertrophy might attenuate or abolish the functional response to reperfusion.
      METHODS: Three groups of chronically instrumented, conscious dogs (dogs with left
      ventricular hypertrophy and hypertension; dogs with left ventricular hypertrophy
      and reduced blood pressure and a control group without hypertrophy and with
      normal blood pressure) underwent 15 min of ischemia and 24 h of reperfusion.
      Segmental systolic thickening was measured by sonomicrometers and myocardial
      segments were grouped by percent of control segmental systolic thickening
      retained at 15 min of ischemia (class 1 greater than or equal to 67%, class 2
      from 0% to 66%, class 3 less than 0% control systolic thickening). The recovery
      of each class of segment was measured serially during reperfusion. Hemodynamic
      variables and regional myocardial blood flow were also measured. RESULTS: There
      were no differences among groups in recovery of segmental systolic thickening for
      class 1 segments. Systolic thickening in class 2 (hypokinetic) segments was
      significantly depressed (p less than 0.05 compared with control value) in the
      group with left ventricular hypertrophy and reduced blood pressure (but not in
      the group with hypertrophy and hypertension) during early reperfusion; systolic
      thickening in class 3 (dyskinetic) segments showed a similar trend in the group
      with hypertrophy and reduced pressure. CONCLUSIONS: Although left ventricular
      hypertrophy with hypertension did not attenuate the contractile response to
      reperfusion, hypertrophy with reduced blood pressure was associated with
      significantly greater depression of segmental systolic thickening early during
      reperfusion.

PMID- 1388185
TI  - Prevalence of latex allergy in operating room nurses.
AB  - The twofold purpose of this study was to assess the prevalence of latex
      sensitivity in a large group of operating room nurses and to evaluate the
      relationship between questionnaire responses and skin tests. Of the total target
      population of 268 operating room nurses, 248 (93%) answered the questionnaire and
      197 had skin prick tests to latex (1/10 wt/vol solution). Symptoms associated
      with glove wearing were acknowledged by 41.1% of nurses. Skin tests to latex were
      positive in 21 nurses (10.7%), 4.4 times more often in atopic nurses. Among
      nurses complaining of local symptoms, only 18.6% had positive skin tests. Itching
      of the hands during glove wearing correlated poorly with latex sensitivity, but
      correlation with local urticaria was better. Atopic nurses complaining of
      urticaria had latex allergy in 70% of cases. Thus latex allergy is common in
      nurses, especially atopic nurses. A questionnaire is unreliable in predicting
      latex sensitivity and must be supported by latex skin test. More data will be
      needed to assess the risk of anaphylactic perioperative reactions in operating
      room nurses.

PMID- 1388186
TI  - Origin and fate of IgE-bearing lymphocytes. II. Gut-associated lymphoid tissue as
      sites of first appearance of IgE-bearing B lymphocytes and hapten-specific IgE
      antibody-forming cells in mice immunized with benzylpenicilloyl-keyhole limpet
      hemocyanin by various routes: relation to asialo GM1 ganglioside+ cells and
      IgE/CD23 immune complexes.
AB  - The organs in which B cells bearing membrane-bound IgE (sIgE+) and
      benzylpenicilloyl (BPO)-specific IgE antibody-forming cells (AFC) first appeared
      were determined in BALB/c mice given BPO-keyhole limpet hemocyanin (10
      micrograms) in aluminum hydroxide by various routes (i.p, gavage, s.c., i.v., or
      i.m.). In mice immunized by the i.p. route, the numbers and location of sIgE+ B
      cells and asialo GM1 ganglioside (AsGm1+) cells, the location of IgE/CD23 immune
      complexes, and the numbers of BPO-specific IgE AFC in lymphoid organs were
      determined. With all routes of immunization, no sIgE+ B cells or BPO-specific IgE
      AFC were ever detected in any organ before day 8. On day 8, with the s.c., i.v.,
      or i.m. routes, sIgE+ B cells and IgE AFC appeared exclusively in Peyer's patches
      (PP); with the i.p. or gavage routes, sIgE+ B cells simultaneously appeared in
      both PP and mesenteric lymph nodes, whereas IgE AFC appeared only in PP. In mice
      immunized by the i.p. route, IgE/CD23 immune complexes and strikingly increased
      numbers of AsGm1+ cells transiently appeared only in PP after the appearance and
      preceding the "disappearance" of the sIgE+ B cells and IgE AFC. The data suggest
      that specific IgE responses originate in gut-associated lymphoid tissue and
      appear later in spleen. The data also associate the appearance of IgE/CD23 immune
      complexes and AsGm1+ cells with the "disappearance" of sIgE+ B cells and IgE AFC
      from PP.

PMID- 1388187
TI  - Microfilament assembly modulates phospholipase C-mediated signal transduction by
      the TCR/CD3 in murine T helper lymphocytes.
AB  - Cytoskeletal involvement in the response to TCR/CD3 ligation and in signal
      transduction was investigated in a murine Th cell type 2 clone. Cells coated with
      the hamster anti-CD3 mAb, 145-2C11 (2C11 mAb), and exposed to goat anti-hamster
      demonstrated an increase in polymerized actin as well as an increase in inositol
      phospholipid hydrolysis mediated by activation of phospholipase C. Pretreatment
      with cytochalasins (Cyt) (D or B), drugs that interact with cellular actin,
      prevented actin polymerization, and augmented the initial rate and total amount
      of inositol phosphates produced. Drugs modifying microtubule function were
      ineffective. The intracellular Ca2+ rise attributed to InsP3 and InsP4 generated
      in response to CD3 perturbation was augmented by CytD. CytD treatment did not
      affect inositol phosphate generation resulting from the stimulation of guanine
      nucleotide-binding proteins with aluminium tetrafluoride, indicating that the
      action of CytD was specific for receptor-mediated inositol phospholipids. CytD
      decreased the rate of anti-CD3-induced receptor internalization. These data
      suggest that the assembly of microfilaments plays a role in CD3 internalization
      and that a CytD-sensitive mechanism uncouples the TCR/CD3 complex from
      phospholipase C-mediated signaling.

PMID- 1388188
TI  - CD45 expression by B cells. Expression of different CD45 isoforms by
      subpopulations of activated B cells.
AB  - To determine the effect of distinct activation stimuli on CD45 expression by B
      cells, we have examined the expression of CD45 molecules on murine B cells
      stimulated with LPS or the Th cell cytokine IL-5. Analysis of CD45 by flow
      cytometry revealed that unstimulated and stimulated B cells expressed homogeneous
      amounts of total CD45 but that stimulation with IL-5 resulted in a CD44hi,
      hyaluronate-adherent subpopulation of activated B cells that expressed a markedly
      altered pattern of expression of exon-specific CD45R or B220 determinants. The
      predominant CD45 immunoprecipitated from either unstimulated or LPS-stimulated B
      cells was of the high molecular mass form (approximately 220 kDa) usually
      associated with B cells. In contrast, the CD45 proteins immunoprecipitated from
      the hyaluronate-adherent subpopulation of IL-5-activated B cells were
      predominantly lower m.w. forms. PCR analysis of amplified CD45 cDNA also showed
      distinct expression profiles characteristic of each B cell population. The
      highest molecular size PCR product, corresponding to expression of all three
      variably expressed CD45 exons (A, B, and C) was prominent in resting B cells and
      in LPS-activated B cells but was selectively reduced in hyaluronate-adherent IL-5
      activated B cells, where lower molecular size PCR products predominated,
      corresponding to expression of one or two of the variable exons. In contrast, LPS
      activated B cells expressed reduced levels of these one- or two-exon forms. In
      addition, all B cell populations expressed a lower m.w. PCR product corresponding
      in size to the product expected when exons A, B, and C are spliced out of CD45
      mRNA. Thus, analysis of alternative splicing of CD45 mRNA, as well as cell
      surface expression of CD45 provides a novel parameter for analysis of B cell
      activation by different stimuli.

PMID- 1388189
TI  - Activation requirements for CD4+ T cells differing in CD45R expression.
AB  - Murine CD4+ T cells can be subdivided into naive and memory T cells based on
      surface phenotype, on recall response to Ag, and on differences in activation
      requirements. Furthermore, several studies have shown that two signals are
      required for CD4+ T cell activation; one signal is provided by occupancy of the
      TCR and the other signal is provided by the APC. In this report, analysis of
      naive and memory CD4 T cells, separated on the basis of CD45 isoform expression,
      has shown that their requirements for two signals differ. Activation of memory
      CD4 T cells to proliferate and secrete IL-2/IL-4 only required occupancy of the
      TCR complex, whereas activation of naive CD4 T cells required an APC-derived
      signal as well. Moreover, the signal induced by anti-CD3 antibodies differs from
      the signal provided by anti-V beta cross-linking of the TCR because both
      antibodies activate memory CD4 T cells but only anti-CD3 activates naive CD4 T
      cells. Together these data suggest that the consequence of stimulation through
      the TCR/CD3 signal complex differs between memory and naive CD4 T cells.

PMID- 1388190
TI  - Activation requirements of newborn thymic gamma delta T cells.
AB  - We have analyzed the requirements for the induction of proliferative responses by
      thymic CD4-CD8- gamma delta T cells. Enriched populations of CD4-CD8- thymocytes
      from newborn mice, purified by negative selection with anti-CD4, anti-CD8, and
      anti-TCR alpha beta mAbs were found to contain approximately 20% gamma delta T
      cells that were p55IL-2R-. When these cells were cultured with a panel of
      lymphokines (IL-1, -2, -4, and -7), a small response was observed to some of the
      cytokines tested individually; however, combinations of certain lymphokines (IL-1
      + 2, IL-1 + 7, and IL-2 + 7) were found to induce significant proliferation and
      the selective outgrowth (75-90%) of gamma delta T cells. These cells were IL-2R+,
      remained CD4-, yet expressed variable levels of CD8. A limited analysis with
      specific anti-V gamma and V delta mAb suggested that there had not been a
      selective expansion of preexisting V gamma 2, V gamma 3, or V delta 4 populations
      in response to the stimulatory lymphokine combinations. Thymic CD4-CD8- gamma
      delta T cells were unresponsive to stimulation with immobilized anti-pan gamma
      delta mAb alone. However, in the presence of immobilized anti-pan gamma delta mAb
      and IL-1, IL-2, or IL-7, but not IL-4, a vigorous proliferative response was
      observed. Phenotypic analysis showed that 80 to 95% of the proliferating cells
      were polyclonally expanded gamma delta T cells, expressed the p55IL-2R, and the
      majority remained CD4-CD8-. Blocking studies with anti-IL-2R mAb showed that
      stimulation with anti-pan gamma delta + IL-1, but not anti-pan gamma delta + IL-7
      was dependent on endogenously produced IL-2. Collectively, these studies suggest
      that the activation requirements of newborn thymic gamma delta T cells differ
      markedly from alpha beta T cells in that gamma delta T cells 1) respond to
      combinations of cytokines in the absence of TCR cross-linking, 2) can respond to
      TCR cross-linking in the presence of exogenous cytokines, 3) but are unable to
      activate endogenous cytokine production solely in the presence of TCR cross
      linking.

PMID- 1388192
TI  - Complex inositol polyphosphate response induced by co-cross-linking of CD4 and Fc
      gamma receptors in the human monocytoid cell line U937.
AB  - The cell-surface Ag CD4, which is characteristic for Th lymphocytes, can also be
      found with a lower density on monocytes/macrophages. Co-cross-linking of CD4 and
      Fc gamma R by an anti-CD4 mAb (MAX.16H5) and by excess of goat anti-mouse Ig
      induced a biphasic increase of the free cytosolic Ca(2+)-concentration ([Ca2+]i)
      in the human monocytoid cell line U937 as measured by FURA-2 fluorescence. A
      rapid rise from 100 to 150 nM [Ca2+]i to 750 to 900 nM within 1 min was followed
      by a decline to about 200 to 300 nM within the next 2 to 3 min. This kinetic is
      characteristic also for blood monocytes and differs significantly from CD4
      mediated Ca(2+)-mobilization in T lymphocytes. The rise in [Ca2+]i in U937 cells
      was not observed when F(ab)2 fragments of MAX.16H5 and F(ab)2 fragments of the
      cross-linker were used indicating the involvement of Fc gamma R. Time course
      analysis using HPLC and a recently developed post-column dye system for mass
      analysis revealed a complex inositol polyphosphate response with rapid increases
      not only in inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate,
      but also in D/L-inositol 1,4,5,6-tetrakisphosphate, inositol 1,3,4,5,6
      pentakisphosphate, and inositol hexakisphosphate after co-cross-linking of CD4
      and Fc gamma R. In conclusion, co-cross-linking of CD4 and Fc gamma R, which may
      occur in vivo during HIV infection or treatment with therapeutic anti-CD4
      antibodies, appears to be a strong activation mechanism for the inositol
      polyphosphate/Ca2+ signal transduction pathway in U937 cells.

PMID- 1388191
TI  - Functional comparison of Fc epsilon RI, Fc gamma RII, and Fc gamma RIII in mast
      cells.
AB  - The cellular responses initiated by cross-linking rodent Fc gamma RII-b1, Fc
      gamma RII-b2, Fc gamma RIII, and Fc epsilon RI in mast cells were compared.
      Individual murine Fc gamma R isoforms were transfected into rat basophilic
      leukemia cells and after cross-linking the FcR, changes in the phosphorylation of
      protein tyrosines, in the level of intracellular Ca2+, in the hydrolysis of
      phosphoinositides, and in the release of arachidonic acid metabolites and
      hexosaminidase were monitored. Cross-linking of Fc gamma RIII initiated all of
      these early and late biochemical functions, and although they were quantitatively
      somewhat smaller, the responses were qualitatively indistinguishable from those
      stimulated by the endogenous Fc epsilon RI. However, despite ample expression,
      neither Fc gamma RII-b1 nor Fc gamma RII-b2 stimulated these functions when cross
      linked. The functional differences between Fc gamma RII and Fc gamma RIII were
      studied further by assessing the responses to cross-linking of the endogenous Fc
      gamma R (Fc gamma RII-b1, Fc gamma RII-b2, and Fc gamma RIII) on P815 mouse
      mastocytoma cells that had been transfected with normal or functionally defective
      Fc epsilon RI. Two types of mutant subunits had previously been observed to
      impair the activity of Fc epsilon RI: gamma-chains missing the cytoplasmic
      domain, and beta-chains missing the COOH-terminal cytoplasmic domain. In both
      types of transfectants the functional inhibition of the endogenous Fc gamma R
      paralleled that of the transfected Fc epsilon RI. These results are consistent
      with the gamma subunit being associated with the functions of Fc gamma RIII as
      well as of Fc epsilon RI. The functional results also complement the recently
      reported evidence that Fc gamma RIII can interact with Fc epsilon RI beta
      subunits (J. Exp. Med. 175:447, 1992).

PMID- 1388193
TI  - Heterogeneous mechanisms of human cytotoxic T lymphocyte generation. I.
      Differential helper cell requirement for the generation of cytotoxic effector
      cells from CD8+ precursor subpopulations.
AB  - The subpopulations of CD8+ T cells defined by CD45RA Ag expression have been
      hypothesized to represent cells varying in their relative maturation along a
      common, activation-dependent differentiation pathway. Previous studies have shown
      that both the CD8+CD45RA+ and CD8+CD45RA- subsets contain precursor cells capable
      of developing into alloreactive CTL. In the current study, we have examined the
      mechanisms involved in the generation of CTL effector cells from these two CD8+
      subsets. Purified CD8+CD45RA+ or CD8+CD45RA- cells were stimulated with
      allogeneic non-T cells, either alone or in the presence of CD4+ Th cells.
      Although the generation of CTL from CD8+CD45RA- precursor cells consistently
      required the presence of CD4+ Th cells, cytotoxic effector cells could be
      generated from CD8+CD45RA+ precursor cells in the absence of CD4+ cells. Several
      lines of evidence indicated that the helper cell-independent generation of
      cytotoxic effector cells from CD8+CD45RA+ precursors resulted from the unique
      ability of this subset to produce and use IL-2 in an autocrine fashion: 1)
      exogenous IL-2 could replace the effects of CD4+ helper cells for either CD8+
      subset; 2) the helper cell-independent functional maturation of CD8+CD45RA+ cells
      could be blocked by anti-CD25 or anti-IL-2 antibodies; and 3) CD8+CD45RA+ cells
      produced IL-2 after activation with allogeneic cells. The finding that precursors
      for helper cell-independent CTL generation are restricted to the CD8+CD45RA+
      subset suggests that this capability may vary as a function of the maturation of
      CD8+ cells.

PMID- 1388194
TI  - Tumor necrosis factor-alpha and IFN-gamma expression in human thymus.
      Localization and overexpression in Down syndrome (trisomy 21).
AB  - In vitro studies suggest that TNF-alpha and IFN-gamma regulate thymocyte
      proliferation, but little evidence exists for the constitutive production of
      these cytokines in normal human thymus. In paired experiments, we examined frozen
      sections of postnatal human thymus from four control children and four age
      matched children with Down syndrome (DS) (trisomy 21) for TNF-alpha and IFN-gamma
      mRNA expression using in situ hybridization. We studied thymuses from children
      with DS because this aneuploid condition is associated with a greatly increased
      incidence of infection and has abnormal thymic anatomy and patterns of thymocyte
      maturation. We found cells expressing constitutive levels of TNF-alpha mRNA in
      the trabeculae, corticomedullary junctions, and medulla of both control and DS
      thymuses and the number of these cells was an average of 3.9-fold higher in DS
      thymuses than in age-matched control thymuses. DS thymuses also contained an
      average of 3 fold higher numbers of cells with mast cell morphology, identified
      by toluidine blue histologic staining and electron microscopy. In both DS and
      control thymuses the mast cells colocalized with TNF-alpha mRNA-expressing cells.
      In addition, TNF-alpha protein- expressing cells, identified by
      immunohistochemistry, displayed a granular pattern of staining that is
      characteristic of mast cells. These results suggest that mast cells may be one
      source of TNF-alpha in human postnatal thymus. Discrete cells expressing IFN
      gamma mRNA were distinctly localized to the cortical region of both DS and
      control thymuses and were 2.4-fold more abundant in DS thymuses than in the
      controls. Our results demonstrate, for the first time, the constitutive
      production and location of TNF-alpha and IFN-gamma in postnatal human thymus. The
      overexpression of both of these cytokines in DS thymuses suggests a dysregulation
      in cytokine production in DS and may provide an explanation for the abnormal
      thymic anatomy and thymocyte maturation associated with this syndrome.

PMID- 1388195
TI  - Reconstitution of long-term T helper cell function after zidovudine therapy in
      human immunodeficiency virus-infected patients.
AB  - Peripheral blood mononuclear cells from 12 asymptomatic patients infected with
      immunodeficiency virus (HIV) and 4 patients with AIDS were analyzed before and
      during therapy with zidovudine for T helper cell (Th) function. Th function
      improved by more than fourfold to one or more of three stimuli tested in 9 (75%)
      of 12 asymptomatic patients on zidovudine therapy and in 3 of 4 patients with
      AIDS. Only 6 (7.4%) of 80 untreated HIV-infected control patients showed
      spontaneous improvement in Th function (P less than 10(-6)). Improved Th function
      was detected as early as 5 weeks into therapy in 6 patients and continued to be
      evident for greater than 1 year after start of therapy in 6 patients and for
      greater than 2 years in 2 patients. No correlation was observed between improved
      Th function and changes in CD4+ or CD8+ cell numbers or in levels of serum HIV
      p24 antigen or beta 2-microglobulin. These results suggest inclusion of in vitro
      Th function as a useful marker in determining the efficacy of antiretroviral drug
      therapy of HIV-infected patients.

PMID- 1388196
TI  - The Gambia Hepatitis Intervention Study: follow-up of a cohort of children
      vaccinated against hepatitis B.
AB  - Hepatitis B vaccine has been introduced into The Gambia's national Expanded
      Programme on Immunization, with the aim of evaluating the impact on chronic liver
      diseases and in particular on hepatocellular carcinoma. As part of the project, a
      cohort of 1000 children was recruited to assess the long-term protection induced
      by the vaccine. The first 3 years of follow-up are described. By the age of 3
      years, 95% of the children had protective antibody levels; 4 (0.6%) are known to
      be carriers in contrast to the 90-140 that would be expected in the absence of
      vaccination. The protective effectiveness of vaccine in preventing chronic
      carriage in the first 3 years of life is thus estimated as 95%. Since the risk of
      becoming a carrier is highest in those infected early in life, these results are
      encouraging.

PMID- 1388197
TI  - Recombinant DNA hepatitis B vaccination in teenagers: effect of a booster at 5
      1/2 years.

PMID- 1388198
TI  - Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis.
AB  - The relationship between apoE phenotype and plasma lipid levels was analyzed in
      the combined data of published studies. Accordingly, 45 population samples from
      17 different countries were included in the analysis. The mean plasma values of
      cholesterol (CH), triglyceride (TG), and high density lipoprotein (HDL)-CH of the
      apoE 2/2, 3/2, 4/3, 4/4, and 4/2 groups were compared with the same parameters of
      the E 3/3 subset. The standardized difference between the plasma lipid
      concentrations of the apoE subgroups and of their respective apoE 3/3 control (Z
      score), as well as their mean weighted value, were calculated for each study and
      in each subgroup. The analysis confirmed that subjects carrying the epsilon 2 and
      epsilon 4 alleles had, respectively, lower (Z2/2 = -0.39, Z3/2 = -0.34) and
      higher (Z4/3 = 0.15, Z4/4 = 0.29) plasma cholesterol values than subjects
      carrying the epsilon 3/epsilon 3 genotype. In addition, results indicated a
      consistent relationship between plasma TG levels and apoE phenotype among
      different populations. TG concentrations were significantly higher in apoE 2/2,
      3/2, 4/3 and E 4/2 than in E 3/3 subsets (Z2/2 = 0.42, Z3/2 = 0.14, Z4/3 = 0.13,
      Z4/2 = 0.19). Further, this trend was found in samples of normolipidemic adults
      and children, in diabetic and obese individuals, as well as in hyperlipidemic
      subjects indicating an ubiquitous relationship. Concurrently, HDL-CH was
      significantly lower in the apoE 4/3 (Z4/3 = -0.09) than in the E 3/3
      subset.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388199
TI  - Huntington's disease in Chinese: a hypothesis of its origin.
AB  - The period prevalence (1984-91) of Huntington's disease (HD) in Hong Kong Chinese
      was 3.7 per million population. HD patients in Mainland China and Hong Kong
      showed similar hereditary pattern, clinical and pathological features as in the
      West. Chinese HD patients were male predominant with a younger age of onset and
      death. Their ancestral origin could be traced mostly to the coastal provinces of
      China. It is proposed that Chinese HD patients may have a European origin and
      share the same gene pool as their white counterparts.

PMID- 1388201
TI  - Age-dependence of effects of A1 adenosine receptor antagonism in rat hippocampal
      slices.
AB  - 1. Population excitatory postsynaptic potentials (EPSPs) and population spikes
      evoked in area CA1 of hippocampal slices from aged Fischer 344 rats were
      significantly smaller in amplitude than responses obtained in slices from young
      Fischer 344 rats. 2. The A1 adenosine receptor antagonist 8
      cyclopentyltheophylline (8-CPT) produced a concentration-dependent increase in
      synaptic potentials in slices from both young and aged rats. Low concentrations
      (1 nM) of 8-CPT were effective in producing increases in both population spike
      amplitudes and population EPSP slopes in young and aged rat slices. Response
      increases were maximized by 100 nM 8-CPT in slices from rats of both age groups.
      3. Adenosine antagonism produced greater average increases in synaptic responses
      in hippocampal slices from aged rats at all concentrations tested (1.0 nM-1.0
      microM). A qualitative age-related difference in the response to 8-CPT was also
      observed; 8-CPT produced a late component, consisting of multiple population
      spikes, in evoked responses in slices obtained from aged but not young rats. 4.
      Adenosine antagonism significantly increased the maximum evocable response (both
      spike amplitude and EPSP slope) in slices from aged rats, relative to increases
      observed in slices from young rats. This suggested that smaller synaptic
      potentials seen in slices from aged rats were in part due to greater levels of
      "tonic" adenosinergic inhibition. 5. Slices from young and aged rats were
      incubated in the adenosine reuptake inhibitor soluflazine (R64719; 1.0, 10, and
      100 microM) and the inhibition of population EPSPs was observed for 60 min. No
      difference was observed in the rate of inhibition or the maximal level of
      inhibition produced by soluflazine, in slices from rats of either age group. 6.
      Application of (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclo-hepten- 5,10
      imine hydrogen maleate (MK-801) and 2-amino-5-phosphonopentanoic acid (2-AP5),
      antagonists of N-methyl-D-aspartate (NMDA) excitatory amino acid (EAA) receptors,
      reduced the late multiple population spike component in slices from aged rats
      incubated in 8-CPT. A smaller direct effect of the NMDA antagonists was observed
      in slices from aged rats in the absence of 8-CPT treatment at maximal response
      levels. No effect of NMDA receptor antagonism was observed in slices from young
      rats under either condition. 7. Hippocampal tissue, from young and old rats
      utilized in the electrophysiological experiments, was assayed for A1 adenosine
      binding site density with a saturating concentration of radiolabeled agonist and
      antagonist. Guanine nucleotide modulation of agonist binding was also
      measured.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1388200
TI  - Electrophysiology of glutamate neurotoxicity in vitro: induction of a calcium
      dependent extended neuronal depolarization.
AB  - 1. Physiological responses of hippocampal pyramidal neurons in primary culture to
      prolonged glutamate (GLU) exposure (500 microM in all experiments) were studied
      with the use of patch electrodes and whole-cell current-clamp recording
      techniques. In some experiments, perforated patch recordings were employed with
      electrodes containing the pore-forming antibiotic nystatin. 2. After washout of
      GLU after a 10-min exposure, pyramidal neurons remained depolarized by greater
      than or equal to 20 mV from rest for the duration of the recording (30 min to
      less than 4 h). This depolarization was accompanied by a 57.8% increase in
      membrane conductance and was termed an extended neuronal depolarization (END).
      The percentage of neurons in which END was induced varied with the duration of
      GLU exposure, with a 4-, 6-, 8-, 10-, and 20-min GLU exposure eliciting END in
      12.5, 41.7, 81.8, 100, and 100% of neurons. END induction appeared to be an all
      or-none phenomenon, because END levels did not differ when compared across GLU
      exposure times. 3. During the END, cells retained both the ability to fire action
      potentials and the ability to respond to GLU, appeared viable when examined
      anatomically, and still excluded vital dyes. This supports the conclusion that
      END is not a nonspecific consequence of cell death. Rather, END is a discrete
      physiological process triggered by prolonged GLU exposure. The results raise
      questions concerning the reversibility of END induction, i.e., can neurons be
      "rescued" once END is induced, or will these cells inevitably go on to die? 4.
      END induction was dependent on a rise in intracellular free calcium ([Ca]i). END
      was prevented by strong buffering of [Ca]i or by substitution of external Ba2+
      for Ca2+. However, substitution of Mn2+ for Ca2+ still permitted END induction.
      In cells recorded with the perforated-patch technique, maintaining normal [Ca]i
      levels, END could be induced, but less readily than under unbuffered [Ca]i
      conditions. 5. END could not be induced by a 10- to 20-min current-clamp
      depolarization to 0 mV, nor by 10-min GLU application while the membrane
      potential was voltage clamped at rest in a solution containing 1 mM Mg2+. In
      addition, END induction by GLU could be blocked by application of MK-801 (10-30
      microM) but not 6-cyano-7-nitroquinoxaline-2,3-dione [CNQX (100-200 microM)]. 6.
      The dependence of both delayed neuronal cell death and END induction on GLU
      exposure duration were similar.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1388202
TI  - Secretion of vitamin A and retinol-binding protein into plasma is depressed in
      rats by N-(4-hydroxyphenyl)retinamide (fenretinide).
AB  - In clinical trials the cancer preventive drug N-(4-hydroxyphenyl)retinamide (HPR)
      markedly lowers plasma concentrations of retinol and retinol-binding protein
      (RBP). Five hours after injection of HPR (51 mumol/kg), serum concentrations of
      retinol and RBP were 33 and 42% lower, respectively, than control values in rats.
      Because the mean transit time for retinol disappearance from serum of HPR-treated
      rats (1.9 h) was similar to that for radiolabeled retinol in control rats in
      previous studies, plasma retinol turnover is apparently not accelerated by HPR
      treatment. To study the effects of HPR on the secretion of the retinol-RBP
      complex from liver, control or HPR-treated rats were injected with chylomicrons
      containing [3H]vitamin A and [14C]triglycerides. Both labels were rapidly cleared
      from plasma in the two groups. In control rats [3H]retinol concentrations began
      to increase in plasma after 30 min due to liver secretion of retinol bound to
      RBP. In HPR-treated rats, secretion was apparently inhibited because the amount
      of [3H]retinol bound to RBP at 4.66 h was only 2.6% of the control level. We
      conclude that HPR partially blocks the secretion of the retinol-RBP complex from
      liver and other tissues, and thus depresses plasma concentrations of vitamin A
      and RBP.

PMID- 1388203
TI  - A submucosal mass in the floor of the mouth.

PMID- 1388205
TI  - Potent indole- and quinoline-containing N-methyl-D-aspartate antagonists acting
      at the strychnine-insensitive glycine binding site.
AB  - The N-methyl-D-aspartate (NMDA)-preferring glutamate receptor subtype possesses,
      in addition to the recognition site for glutamate, a binding site for glycine. We
      report here on the pharmacological properties of 3-(4,6-dichloro-2-carboxyindol-3
      yl)-propionic acid (MDL 29,951) and 4-carboxymethylamino-5,7-dichloroquinoline-2
      carboxylic acid (MDL 100,748), two novel glycine antagonists of NMDA receptor
      activation in vitro and in vivo. We have measured in parallel the effects of two
      previously described glycine antagonists, 7-chlorokynurenic acid and 5,7
      dichlorokynurenic acid. All were potent inhibitors of [3H]glycine binding. Ki
      values (microM) were 0.36 (7-chlorokynurenic acid), 0.08 (5,7-dichlorokynurenic
      acid), 0.07 (MDL 100,748) and 0.14 (MDL 29,951). MDL 100,748 and MDL 29,951 were
      approximately 2000-fold selective for the glycine binding site relative to the
      glutamate recognition sites. All four compounds completely inhibited the use
      dependent binding of [3H]N-[1-(2-thienyl) cyclohexyl]-piperidine and were
      noncompetitive, glycine-reversible inhibitors of both NMDA-induced biochemical
      and electrophysiological responses in brain slice preparations. A competitive
      interaction with the glycine binding site was also evident in that MDL 29,951 and
      MDL 100,748 produced parallel rightward shifts in the glycine requirement for
      demonstration of NMDA-stimulated elevations in cytosolic calcium in cultured
      neuronal preparations. The glycine antagonists were potent anticonvulsants after
      their i.c.v. administration to audiogenic seizure-susceptible DBA/2J mice.
      Because the compounds chosen encompass a variety of chemical structures, the
      results indicate that glycine is required for NMDA receptor activation and that
      bioavailable glycine antagonists may form the basis of a novel therapy for
      epilepsy.

PMID- 1388204
TI  - Enhanced sensitivity to the behavioral effects of cocaine after chronic
      administration of D2-selective dopamine antagonists in the squirrel monkey.
AB  - The behavioral effects of cocaine (0.03-3.0 mg/kg i.v.) were determined in
      squirrel monkeys (Saimiri sciureus) trained to respond under a fixed-interval 300
      sec schedule of stimulus termination. A session consisted of 13 consecutive fixed
      interval components, each followed by a 60-sec timeout. Graded doses of cocaine
      were injected during selected timeout periods using a cumulative-dosing
      procedure. Subsequently, two dopamine D2-selective antagonists, spiperone and
      raclopride, and a D1-selective antagonist, SCH 23390, were administered
      chronically for a 2-week period. Due to pronounced time course differences,
      raclopride and SCH 23390 were infused continuously via osmotic minipump, and
      spiperone was administered i.m. twice per week. Spiperone and raclopride markedly
      suppressed responding during the 2-week period. When the effects of cocaine were
      redetermined 3 days after spiperone or 1 day after raclopride administration was
      terminated, there was a parallel leftward shift in the dose-effect curve,
      indicating enhanced sensitivity to cocaine. Three days later, sensitivity to
      cocaine had changed and was similar to that obtained before chronic drug
      administration. In contrast, SCH 23390 did not alter sensitivity to cocaine after
      chronic administration was terminated, even though it did attenuate the
      behavioral effects of cocaine as effectively as spiperone and raclopride. Chronic
      administration of spiperone did not alter sensitivity to nisoxetine, a
      norepinephrine uptake inhibitor, or quipazine, a serotonin agonist. The acute
      administration of spiperone in combination with cocaine also differed markedly
      from nisoxetine and quipazine. The pronounced rate-decreasing effect of spiperone
      was attenuated by cocaine in a dose-dependent manner, but not by nisoxetine or
      quipazine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388206
TI  - Determination of the absolute configuration of the active amlodipine enantiomer
      as (-)-S: a correction.
AB  - The active (-) enantiomer of amlodipine was originally reported to have R
      configuration. This does not concur with other 1,4-dihydropyridines with known
      absolute configuration. This configuration has now been determined by X-ray
      structural analysis using (1S)-camphanic acid and (S)-2-methoxy-2-phenylethanol
      as chiral probes. Both determinations gave the S configuration for the amlodipine
      (-) enantiomer with the greater Ca-antagonistic activity.

PMID- 1388207
TI  - Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring
      system. 1.
AB  - A series of 11-[[2-[(arylsulfonyl)amino]ethyl]thio]-6,11-
      dihydrodibenz[b,e]oxepin-2-carboxylic acids and related derivatives were
      synthesized. The compounds were tested for their antagonizing effects on guinea
      pig platelet TXA2/PGH2 receptors. Structure-activity relationships are discussed.
      (+/-)-11-[[2-[(Styrylsulfonyl)amino]ethyl]-thio]-6,11- dihydrodibenz[b,e]oxepin-2
      carboxylic acid (41) and (+/-)-11-[[2-[(phenylsulfonyl)amino]ethyl]thio]-6,11-
      dihydrodibenz[b,e]thiepin-2-carboxylic acid (4af) were the most promising
      compounds with K(i) values of 6.5 +/- 0.29 and 3.7 +/- 0.31 nM, respectively, for
      the TXA2/PGH2 receptor. These compounds also significantly inhibited U-46619
      induced guinea pig platelet aggregation ex vivo (10 mg/kg po). Compound 41 was
      resolved into its optically active form. The (-)-isomer was 60-fold more potent
      than the (+)-isomer in the TXA2/PGH2 receptor binding assay. Some compounds
      tested in this study showed both TXA2/PGH2 receptor antagonizing and TXA2
      synthase inhibitory effects.

PMID- 1388208
TI  - Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring
      system. 2.
AB  - A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2-
      carboxylic acid derivatives and related compounds were synthesized and found to
      be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested
      for its ability to displace [3H]U-46619 binding from guinea pig platelet
      TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the
      following key elements were required for enhanced activities: (1) an (E)-2-(1
      benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring
      system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring
      system. The studies also indicated that the TXA2/PGH2 receptor binding affinities
      of this series of compounds in guinea pig platelet were poorly correlated with
      those in human platelet. Introduction of substituent(s) to the benzimidazole
      moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1
      benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate
      monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2
      receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory
      effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo)
      and human platelet aggregation (in vitro). Compound 57, now designated as KW
      3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with
      neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is
      now under clinical evaluation.

PMID- 1388209
TI  - Terminal regions of the NS-1 protein of the parvovirus minute virus of mice are
      involved in cytotoxicity and promoter trans inhibition.
AB  - The nonstructural (NS) transcription unit of minute virus of mice (MVMp) encodes
      proteins that are involved in viral DNA replication and in the regulation of
      homologous and heterologous promoters. Moreover, it has been shown that NS
      protein accumulation is toxic for transformed cells. With the aim of identifying
      the NS-protein function(s) responsible for cytotoxicity, point mutations and
      deletions were introduced in the NS-protein-coding sequence of MVMp. This
      strategy indicated that in transformed human NBE cells, the NS-1 protein is
      indispensable for MVMp DNA replication, trans activation of the late parvoviral
      promoter P38, trans inhibition of the long terminal repeat promoter of the Rous
      sarcoma virus, and cytotoxicity. Moreover, some mutations led to the dissociation
      of the replicative and regulatory functions of the NS-1 protein and showed that
      cytotoxicity correlated with the latter, more particularly with the capacity to
      trans inhibit the heterologous promoter. The NS-1 sequences required for
      cytotoxicity were found to be restricted to the amino- and carboxy-terminal
      portions of the protein. Although the cytotoxicities of NS-1 extremities were
      weak when the extremities were tested separately, the cytotoxicities were
      comparable to that of the full protein when the extremities were fused.
      Interestingly, an overall negative charge can be predicted from the NS-1 sequence
      over about 100 amino acids at both ends. The conservation of this charge
      distribution among the NS proteins of different parvoviruses suggests that NS-1
      may bear some similarities to acidic transcriptional activators.

PMID- 1388211
TI  - Effects of reperfusion on left ventricular ejection fraction and volume after
      acute myocardial infarction.
AB  - The effects of reperfusion on left ventricular (LV) function and volume were
      studied in patients with evolving acute myocardial infarction (AMI). We analyzed
      the LV ejection fraction and volume in patients who had been admitted within 24 h
      of the onset of their first AMI with culprit lesion of #6, #7 and #1 (American
      Heart Association classification). Sixty-five patients (Re group) received
      successful reperfusion therapy within 6 h after the AMI. The other 60 patients
      (Oc group), who were admitted from 6 to 24 h after the AMI, received conservative
      therapy. Patients with re-obstruction of the culprit lesion after reperfusion
      therapy were excluded from the Re group. Patients with spontaneous recanalization
      following conservative therapy were excluded from the Oc group. The LV ejection
      fraction (LVEF), LV end-systolic volume index (LVESVI), and LV end-diastolic
      volume index (LVEDVI) were measured using a modified Dodge's formula by left
      ventriculography performed 4 weeks after the AMI. LVEF in the Re group was
      significantly greater than in the Oc group (57 +/- 12 vs 49 +/- 11%) (mean +/-
      SD, p less than 0.01). LVESVI in the Re group was significantly smaller than in
      the Oc group (30 +/- 13 vs 38 +/- 16 ml/m2, p less than 0.01). Although LVEDVI
      was not significantly different between the 2 groups, in patients with a
      responsible coronary lesion of segment #6, LVEDVI in the Re group was
      significantly smaller than in the Oc group (67 +/- 14 vs 77 +/- 18 ml/m2, p less
      than 0.05). Although LVEF and LV volume correlated in both groups, the
      correlation was weak (r = 0.40-0.42), suggesting that LV volume was not dependent
      solely on LV functional recovery. The incidence of ventricular aneurysm in the Re
      group was significantly lower than in the Oc group (15.4 vs 45.0%, p less than
      0.01). Multivariate analysis selected reperfusion of the responsible coronary
      artery as one of the factors significantly associated with a reduction of LVEDVI,
      LVESVI, an improvement of LVEF, and a decrease in the rate of aneurysm formation.
      In summary, our results indicated that reperfusion improved EF, reduced LV
      volume, and decreased the rate of aneurysm formation as compared to non
      reperfusion, which suggests that reperfusion therapy is beneficial for both
      functional recovery and ventricular remodeling.

PMID- 1388210
TI  - Map of cis-acting sequences that determine alternative pre-mRNA processing in the
      E3 complex transcription unit of adenovirus.
AB  - The E3 complex transcription unit of adenovirus encodes four major mRNAs (a, c,
      f, and h) and two minor (d and e) mRNAs with overlapping exons, alternative
      splice sites, and two polyadenylation sites, termed E3A (upstream) and E3B
      (downstream). mRNAs a and d use the E3A polyadenylation site, and mRNAs c, e, f,
      and h use the E3B site. We have analyzed virus mutants with deletions throughout
      the E3 region in order to identify cis-acting sequences that function in E3 pre
      mRNA processing. The results presented in this report as well as previous results
      are summarized as follows. (i) Deletions in the first (5') intron at nucleotides
      (nt) 372 to 768 in E3 had no effect unless they removed the consensus sequence
      for the nt 372 5' splice site; however, the overall pattern of E3 mRNAs did not
      change significantly. (ii) Deletions in region I (nt 1441 to 2044) eliminated
      mRNAs a and c and resulted in corresponding increases in mRNAs f and h; we
      propose that region I contains sequences that suppress splicing. (iii) Mutations
      in region II (nt 2161 to 2243) resulted in nearly exclusive synthesis of mRNA f;
      this phenotype is understood and is discussed. (iv) Changing the AUUAAA component
      of the E3A poly(A) addition signal to AAUAAA resulted in increased mRNA a levels,
      suggesting that the E3A poly(A) addition signal is intrinsically inefficient. (v)
      Deletions in region III (nt 2488 to 3002) decreased mRNA a levels about two- to
      threefold and specifically increased mRNA f levels; we suggest that region III
      facilitates use of the E3A polyadenylation site. (vi) Deletions in region IV (nt
      2904 to 3251) increased mRNA a levels about two- to threefold; we suggest that
      region IV may contain sequences that facilitate use of the E3B polyadenylation
      site. A map of sequences that determine alternative pre-mRNA processing in region
      E3 is now nearly complete.

PMID- 1388212
TI  - [Effect of antihypertensive treatment in elderly hypertensive patients with
      cardiac hypertrophy].
AB  - In elderly hypertensive patients effect of antihypertensive treatment with Ca
      antagonist or ACE inhibitor on the heart were examined. Twenty-four elderly
      hypertensive patients with cardiac hypertrophy, aged 65-79 years old (mean +/-
      SEM, 71 +/- 1) were treated with Ca antagonist (nifedipine or nicardipine) or ACE
      inhibitor (captopril or enalapril) for 3 months. Thirteen patients had essential
      hypertension (EH: SBP greater than or equal to 160 mmHg and DBP greater than or
      equal to 95 mmHg, 70 +/- 1 years) and 11 had isolated systolic hypertension (ISH:
      SBP greater than or equal to 160 mmHg and DBP less than 95 mmHg, 74 +/- 2 years).
      Blood pressure (BP) and heart rate were measured every two weeks. In all
      patients, M-mode echocardiography was performed to measure left ventricular mass
      index (LVMI) and ejection fraction (EF), and the sympathetic nervous (plasma
      norepinephrine and epinephrine) and the renin-angiotensin system (plasma renin
      activity and aldosterone concentration), were assessed before and after 3 months
      of treatment. BP significantly decreased from 174 +/- 3/97 +/- 1 to 149 +/- 4/84
      +/- 2 mmHg in EH and from 167 +/- 3/82 +/- 2 to 144 +/- 4/74 +/- 2 mmHg in ISH.
      LVMI was significantly reduced from 204 +/- 14 to 174 +/- 16 g/m2 in EH and from
      179 +/- 14 to 156 +/- 12 g/m2 in ISH. EF showed no significant changes in either
      group. In ISH, the change in LVMI was significantly correlated with the change in
      systolic BP (r = 0.74, p less than 0.05). In EH, there was no significant
      relation between BP and LVMI changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388213
TI  - [Calcium metabolism in various forms of hypertrophy of the "hypertensive" heart].
AB  - To study the changes occurred in integral calcium metabolic parameters in
      evolving "hypertensive" heart, a total of 100 patients with Stage I-II (WHO
      Classification) were examined. Myocardial structure and function were
      echocardiographically examined. Plasma concentrations of ionized calcium were
      measured by direct potentiometry. Plasma levels of calcitonin and parathyroid
      hormone were measured by radioimmunoassay. As the "hypertensive" heart
      progressed, the ionization of serum calcium was found to enhance along with an
      increase in calcitoninemia. In early formation of the "hypertensive" heart,
      parathyroid hormone remained unchanged, but became elevated only in severe left
      ventricular hypertrophy. The findings may explain the features of the clinical
      aspects of variant left ventricular hypertrophies in the "hypertensive" heart.

PMID- 1388214
TI  - [The treatment of acute appendicitis].
AB  - The article deals with the experience in the treatment of 3,368 patients with
      acute appendicitis from 1979 to 1989. Among them were 2,398 adults and 976
      children. Complications developed in 190 (5.6%) patients, 5 (0.15%) patients
      died. The mortality rate among children was 0.3%. Complications and deaths were
      connected with neglected forms of the disease. 695 (20.6%) patients were admitted
      later than 24 hours after the onset of the disease. The patients diagnosed the
      disease themselves and resorted to self-treatment. Health education measures were
      poorly effective; it is suggested that this work should be started from early
      childhood. A permanently functioning seminar on acute surgical diseases was
      organized at the institution for doctors not practicing in surgery, but
      diagnostic errors were made at the prehospital stage in 117 cases by district
      therapists, pediatricians, and the staff of emergency aid teams. There were also
      cases in which operation was undertaken late after admission to the hospital and
      cases of hyperdiagnosis. The late-term results were studied in 109 patients
      without morphological changes in the removed vermiform processes, in 51.4% of
      them other diseases were encountered in the long-term period.

PMID- 1388215
TI  - [The ultrasonic diagnosis of acute appendicitis and its complications].
AB  - The article discusses the possibility of ultrasonic examination (USE) in the
      diagnosis of acute appendicitis and its complications. Forty-five patients were
      examined, 15 of them had a doubtful clinical picture of acute appendicitis and in
      30 destructive acute appendicitis was suspected. During USE the vermiform process
      was not detected in 5 patients, uncomplicated acute appendicitis was diagnosed in
      10 and complicated acute appendicitis (appendicular infiltrate, abscess) in 30
      patients. Eight patients underwent laparoscopy, 29 patients were subjected to an
      operative intervention, 15 patients received a course of nonoperative treatment
      followed by appendectomy 3-6 months later. As the result of the study the USE
      signs of acute appendicitis and its complications were specified. USE may be of
      significant aid to the surgeon in the diagnosis of this disease.

PMID- 1388217
TI  - [Plastic operations in rectal fistulae].
AB  - Experiments were conducted on 48 dogs to study the terms and degree of resolution
      of various plastic materials--areas of fascia lata of the animal's thigh, as well
      as explants (medical glue compositions, biological absorbable lavsan-armored
      Soviet medical films) in the pararectal tissues and in artificial formation of
      rectal fistulas. It is shown that auto- and explantation may be performed in the
      treatment of rectal fistulas in patients. The suggested method was applied in the
      clinic in 136 operations for complex trans- and extrasphincteric pararectal
      fistulas. The results were followed-up for 12 months to 5 years and proved to be
      good in 126 patients.

PMID- 1388216
TI  - [Laparoscopy in the diagnosis of acute appendicitis in pregnant women].
AB  - Diagnostic laparoscopy in 96 pregnant women with suspected acute appendicitis
      revealed inflammation of the vermiform process only in two (2.1%) of them. In 81
      cases acute surgical diseases of the abdominal organs were not found,
      extrauterine pregnancy was revealed in 9 and other diseases of the abdominal
      organs were detected in 4 cases. The threat of abortion was mistaken for acute
      appendicitis most frequently. Unjustified operation in such cases intensifies
      still more the signs of the threat of abortion. Analysis allows the assertion
      that the laparoscopic method should be decisive in the examination of pregnant
      women with a doubtful clinical diagnosis in suspected acute appendicitis.
      Laparoscopy is indicated when the reserves of the generally accepted clinical
      methods and noninvasive instrumental examination do not allow the diagnosis of
      acute appendicitis to be established or excluded; it is also recommended in
      establishing the exact diagnosis and determining the approach and volume of an
      operative intervention when there is a clinical picture of an acute surgical
      disease of the abdominal cavity.

PMID- 1388218
TI  - [Torsion of the colonic epiploic appendages].
AB  - Operations were carried out on 21 patients with torsion of epiploic appendages of
      the colon (sigmoid 19, ascending 1, hepatic flexure 1). This pathologic condition
      has no specific manifestations and occurs under the mask of other emergencies.
      The suggested symptom of "pain displacement" in combination with other signs
      allowed the correct diagnosis to be established before the operation in two
      thirds of patients. Patients with torsion of epiploic appendages must be
      subjected to an emergency operation for removal of the necrotic appendage by
      ligation of its vascular pedicle and its peritonization with seromuscular
      sutures.

PMID- 1388219
TI  - Calcium homeostasis, bone metabolism and safety aspects during long-term
      treatment with a GnRH agonist.
AB  - Thirty-five women with symptomatic fibroids were treated with monthly injections
      of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17
      beta-oestradiol levels decreased, falling to castration levels associated with a
      reduction in the volume of the fibroids. In 16 patients a complete calcium
      homeostasis and bone metabolism work-up was carried out during treatment and
      subsequently for a 6-month follow-up period. Bone mineral content (BMC) and
      Compton bone densitometry readings remained unchanged. There were significant
      increases in serum calcium phosphate and alkaline phosphatase concentrations. A
      slight although not significant increase was observed in osteocalcin and
      parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased
      significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and
      calcium/creatinine ratios as well as 24-h urinary calcium values increased
      significantly during the treatment period but decreased rapidly to pretreatment
      values after 3 months in the follow-up period. The endocrine changes induced by
      the GnRH-agonist treatment were associated with reversible biochemical signs of
      increased bone turnover and no significant changes in bone mass, suggesting that
      the treatment can be administered safely for a period of 6 months in patients
      with oestrogen-dependent diseases.

PMID- 1388221
TI  - Polymeric hydrogel compounds and their application in restorative surgery in
      cases of portal hypertension.
AB  - This paper deals with aspects of developing the biologically-compatible polymeric
      material for filling cavities or deposition of the physiologically-active
      preparations. Determined is the possibility of using the composite material in
      one of the complex fields of restorative surgery, i.e. the syndrome of portal
      hypertension.

PMID- 1388220
TI  - Secretory endometrial protein PP14 in serum from post-menopausal women receiving
      continuous combined oestradiol-cyproterone acetate: correlation with serum
      hormone concentrations and bleeding patterns.
AB  - The secretory endometrial protein PP14 was measured in serum from 49 healthy,
      early post-menopausal women receiving continuous combined oestradiol
      valerate/cyproterone acetate (2 mg E2V + 1 mg CPA daily) or placebo over a period
      of 2 years. In the hormone group, serum PP14 increased from 2.1 micrograms/l to a
      maximum of 8.1 micrograms/l after 1 month of treatment, then fell after 3 months
      to 3.8 micrograms/l and remained at that level for the rest of the 2-year period.
      After the first month, the occurrence of uterine bleeding was associated with
      significantly increased serum PP14 levels. Bleeding was not correlated with the
      serum concentration of 17 beta-oestradiol (E2) or CPA, or the CPA/E2 ratio. Serum
      PP14 was significantly dependent on the serum concentration of E2, but not on
      that of CPA. The present data confirm that serum PP14 levels reflect the
      secretory phase of the endometrium and that bleeding during continuous combined
      hormone replacement therapy is probably caused by a sub-optimal hormonal balance.

PMID- 1388222
TI  - Biomechanical substantiation of design features and physicomechanical
      characteristics of pins made of biocompatible polymers for intraosseous
      osteosynthesis.
AB  - This paper suggests a biomechanical model for osteosynthesis of tubular bones
      with the use of pins made of biocompatible polymers for the substantiation of the
      basic physicomechanical requirements to jointing elements (pins) with regard to
      functional loads, design features of pins and physicochemical properties of the
      materials used. It is shown that the known polymers including the biocompatible
      ones, do not individually possess the necessary strength characteristics for the
      production of jointing elements for highly loaded tubular bones. The properties
      of pins, made of biocompatible polymers, can be increased by optimizing their
      shapes and modifying the materials.

PMID- 1388224
TI  - Objective estimation of human colour vision by means of electroretinography.

PMID- 1388223
TI  - New equipment for stereophlebography.
AB  - Discussed in the present article is the complex of the equipment intended for
      roentgenodiagnosis of the lower limb varicosity and for use in planning the
      operations on the vessels. The complex includes the automatic stereocassette,
      constructed as an attachment to the standard roentgenodiagnostic apparatus, and
      the stereoscope for analyzing the stereophlebograms visually. The article
      provides a description of this equipment and methods of its employment.

PMID- 1388225
TI  - Medical laser mass spectrometric standardless microanalysis.
AB  - This paper deals with application of the laser mass spectrometry method for the
      standardless elementary analysis of the medical and biological samples. Reviewed
      is process of the laser emission interaction with the target substance and ion
      formation. Illustrated is the radical possibility of using laser ionization for
      standardless analysis. The primary criterion of such a possibility is the laser
      emission power density. The obtained results were used for the non-standard
      analysis of the medical and biological samples on the EMAL-2 device series
      produced in the USSR. The mass spectra of the liver tissue and whole blood
      without preliminary preparation (liberation from the organic part) are presented.
      The issues of using this method as regards the sanitary and hygienic,
      toxicological and diagnostic tasks associated with the change in the
      microelementary composition of the tissues and biological fluids are
      substantiated.

PMID- 1388226
TI  - Pulse wave sensors with improved noise immunity.
AB  - Reviewed in this article are the principle of operation and design features of
      the pulse wave sensors realizing the method of space-oriented differentiation for
      the noninvasive arterial pressure meters which can measure pressure during the
      physical tests of a patient. Disclosed are the test results and procedure for
      checking the pulse wave sensors using the nonstandard means of measurement.

PMID- 1388227
TI  - Toxicological aspects of preclinical studies of hemosorbents.
AB  - The main tendencies in the development of methods for hemo- and lymphosorption
      are considered. Base toxicological requirements to sorbents have been formulated.
      Special attention is paid to possible tox effects of sorbents containing
      carcinogenic admixtures. The importance of choosing appropriate methods sorbents'
      sterilization or conservation has been emphasized. Results of studies of various
      sorbents a presented.

PMID- 1388228
TI  - Toxicological estimate of polyvinyl chloride containers for preparation and
      storage of blood, its components, preservatives and infusion solutions.
AB  - Migration of dioctyl phthalate from the polyvinyl chloride containers (PVC
      containers) into blood, its components, preservatives and infusion solutions was
      studied for the purpose of estimating toxicity of the articles. Dependence of the
      plasticizer cumulation on the composition of the media found in the containers
      was discovered. The effect of the storage conditions on the toxicological and
      hygienic characteristics of the containers and intact condition of the
      bioproducts housed therein was investigated. Compliance of the polyvinyl chloride
      containers with the requirements of international standards for estimating
      toxicity of the polymeric materials and articles of medical purpose was
      established.

PMID- 1388229
TI  - Ultrasonic immersion echomammography: state of the art and prospects.
AB  - This article discusses the state of the art and the prospects of evolution of
      ultrasonic immersion mammographs. It is shown that ultrasonic immersion
      mammography for diagnostics of surface organs has a preference over existing
      ultrasonic scanning devices of contact type. An immersion mammograph has been
      developed, a characteristic of which is the use of compact ring multielement
      antenna with the electronic dynamic focusing block.

PMID- 1388230
TI  - Characteristics of MR-tomographers' image and their monitoring.
AB  - Similar to X-ray computer tomography and taking into account the specificity of
      obtaining the MR image a range of characteristics is proposed for the control of
      the MR tomographers' images. On the basis of the literature analysis and our own
      research requirements are formulated to the range and the errors of the MR image
      characteristics guaranteeing the required diagnostics reliability level.
      Proceeding from the requirements to the MR image characteristics the requirements
      are formulated to test objects for their monitoring, including the MR-contrast
      media for test objects. The test objects' structures are described, developed in
      accordance with the formulated requirements.

PMID- 1388231
TI  - New medical-purpose absorbent materials based on polyacrylic acid and alpha
      cyanoacrylates, their structure and properties.
AB  - Hydrophylic porous polymers (HPP) obtained by polymerization of the alpha
      cyanoacrylates under contact with solution of the polymeric carboxylic acids has
      the degree of water absorption up to 50.000 percent. Disclosed are the data on
      the HPP porosity investigation, water absorptions HPP are not toxic, do not
      exhibit allergenic and irritative actions, admit introduction of the medicine
      into HPP. The HPP films and sheets were used in the course of the experiment for
      treatment of purulent wounds. Their high effectiveness expressed in reduction of
      the adhesion time by 1.5 to 2 times was established.

PMID- 1388232
TI  - An electrostimulator to restore sexual function in chronic prostatitis patients.

PMID- 1388233
TI  - Cryoultrasonic and cryogenic equipment for medicine.
AB  - The problem of cryodestruction control in a biological object may be
      characterized by various decisions. This paper deals with technical solutions
      based on the use of cryogenic and cryoultrasonic equipment with different
      technological functions to provide, with an appropriate probability, the required
      and controlled tissue destruction.

PMID- 1388234
TI  - Mathematical modelling of single-seater oxygen pressure chambers. Premises,
      realization, practical results.

PMID- 1388236
TI  - Optimization of X-ray mammography conditions.

PMID- 1388235
TI  - Antimicrobic jointing elements for internal organs made of biocompatible
      polymers.

PMID- 1388237
TI  - Nature and clinical application of human electroretinogram La-wave.

PMID- 1388238
TI  - Audiostimulator for restoration of functions of kidneys and upper urinary tracts.

PMID- 1388240
TI  - Biosoluble polymeric medicinal films.
AB  - This paper offers a brief review of the issues related to selection of the
      polymeric matrix base that determines the possibilities of forming medicinal
      film. Estimated is its efficiency as compared to other polymeric carriers. Also
      discussed are examples of using medicinal films in certain fields of medicine.

PMID- 1388239
TI  - Luminescent screens for general X-ray diagnostics.
AB  - This article gives the main parameters of amplifying screens manufactured in the
      USSR: the sensitivity, the resolution, the modulation depth, the noise. The
      technical level of Soviet screens is compared with the level of those
      manufactured by certain foreign companies. The measures taken to increase the
      technical level of today's products and the further evolution directions are
      discussed. Data are given on screen production in the USSR during the last 5
      years and their supposed production up to 2000.

PMID- 1388241
TI  - Testing of dielectric properties of biological tissues in microwave range for
      solving matching problems.
AB  - Since the employment of microwave energy for defrosting biological tissues and
      for microwave-aided diagnosis in cryosurgery is very promising, the problem of
      ensuring the match between the contact antennas (applicators) and the frozen
      biological object has become a pressing one. It is for this reason that
      investigations were aimed at the study of the dielectric properties of the dog's
      muscular and fatty tissues in a temperature range of +20 to -30 degrees C
      including the phase transition of the samples to the solid state. The
      investigations were performed in a waveguide device using a short-circuit method.
      During the investigation possible error was estimated. The experiment provides
      for the reduction of the error caused by the waveguide linear expansion.

PMID- 1388242
TI  - Medical-purpose elastic materials based on siloxane rubbers and items made from
      them.
AB  - Vulcanization of the unsaturated siloxane rubbers with silicon hydrides of
      various structure (organohydrosiloxanes, organohydrosilazanes,
      organohydrosilanes) was investigated for the purpose of creating biologically
      compatible materials with a high complex of medical and engineering properties.
      The effect of the silicon hydride structure on the vulcanization process and
      properties of the produced rubbers was identified. The basis sanitary and
      hygienic indices of rubbers were studied. A wide range of medical-purpose items
      was manufactured using the developed compounds.

PMID- 1388243
TI  - T and B cell responses to chimeric proteins containing heterologous T helper
      epitopes inserted at different positions.
AB  - The ability of a T helper (Th) epitope to induce help for B cells recognizing
      different determinants within a multideterminant antigen was investigated.
      Chimeric fusion proteins, containing inserts of single or multiple copies of the
      Th epitope ovalbumin 323-339 (ova) at two different positions, were compared with
      respect to their ability to induce specific antibody production and ova-specific
      T cell activation. The antibody responses against B cell determinants at the
      amino and carboxy terminus, respectively was differently influenced by the
      molecular positioning of the inserted Th determinant. All ova-containing fusion
      proteins induced antibody production against the B cell determinant at the amino
      terminal end irrespective of the positioning of ova. In addition, multiple copies
      of ova in any position led to increased levels of antibody production against
      this epitope. In contrast, T cell help for antibody production against the
      determinant at the carboxy terminus was more effective after insertion of
      multiple copies of ova in a distal than in an adjacent position. Furthermore a
      fusion protein, containing four copies of ova effectively elicited T cell help
      for high levels of antibody production against both examined B cell determinants,
      showing that activated Th cells recognizing a single epitope could simultaneously
      provide help for distinct sets of B cells specific for widely separated epitopes
      within a protein. Immunodominant T cell recognition of ova in all chimeric
      peptides, independently of its position, was demonstrated by lymph node cell
      (LNC) proliferation of primed BALB/c mice. The level of ova-specific T cell
      proliferation was similar, irrespective of which chimeric peptide that had been
      used for priming, and thus did not reveal any differences in T cell priming
      efficiencies related to the number of ova copies in the fusion proteins. However,
      when the peptides were presented to a ova-specific T cell line by A20 B lymphoma
      cells, a close correlation between IL-2 production by the clonal T cells and the
      number of ova epitopes in the chimeric peptides was observed. Thus, increased
      cytokine production by ova-specific T cells may be important for the increased
      level of in vivo antibody production observed in response to multiple copies of
      ova in the chimeric antigens.

PMID- 1388244
TI  - RHP is antigenically related to factor H and binds to the globular heads of C1q.
AB  - RHP was purified from normal serum by sequential euglobin precipitation, ion
      exchange chromatography on DEAE-Sephacel and gel filtration using Sephacryl S
      300. RHP reacted with anti-Factor H antibodies in ELISA assays and in Western
      blots, suggesting that it is antigenically related to Factor H. It bound to
      intact C1q but not to the collagen-like N-terminal half of the molecule. C1q
      specific monoclonal antibody BUS-1, which blocks the binding of C1q to immune
      complexes, did not block the binding of RHP to C1q. This implies that the binding
      sites on C1q for IgG and RHP do not overlap.

PMID- 1388245
TI  - Cell biology. New cytoskeletal liaisons.

PMID- 1388246
TI  - Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells.
AB  - Rat basophilic leukaemia cells, like mast cells from which they are derived, have
      surface Fc epsilon receptors that trigger secretion of inflammatory mediators
      when crosslinked. Both GTP-binding proteins and a rise in cytosolic calcium
      concentration ([Ca2+]i) are implicated in the secretory mechanism. Here we use a
      video-imaging technique to report that transient rises in [Ca2+]i initiated in an
      individual cell can spread from cell to cell in a wave-like pattern by means of a
      secreted intermediate, in the absence of gap-junctional communication. We find
      that the leukaemia cells, peritoneal mast cells and mucosal mast cells have cell
      surface P2-type purinergic receptors that can trigger similar [Ca2+]i transients.
      We provide evidence that ATP is rapidly released, and that it can amplify [Ca2+]i
      signals and initial secretory responses during antigen-stimulation of rat
      basophilic leukaemia cells.

PMID- 1388247
TI  - Inhibition of histamine turnover by 8-OH-DPAT, buspirone and 5-hydroxytryptophan
      in the mouse and rat brain.
AB  - The effects of 5-hydroxytryptamine (5-HT) receptor agonists on histamine turnover
      in mouse and rat brains were examined. The histamine turnover rate was estimated
      from the accumulation of tele-methylhistamine 90 min after i.p. injection of
      pargyline (65 mg/kg). In whole mouse brains, the histamine turnover was
      significantly inhibited by the 5-HT1A agonists, 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) (greater than 0.5 mg/kg) and buspirone (greater
      than 2 mg/kg) injected s.c. 10 min before pargyline treatment. 5
      hydroxytryptophan (20 mg/kg) also significantly inhibited histamine turnover.
      Injections of the 5-HT1B agonist m-trifluoromethylphenylpiperazine (10 and 20
      mg/kg) or the 5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1, 2
      and 5 mg/kg), however, did not affect histamine turnover. The inhibitory effect
      of 8-OH-DPAT (1 mg/kg) on histamine turnover was significantly antagonized (by
      40%) by pindolol (20 mg/kg) and slightly antagonized (by 29%) by spiperone (10
      mg/kg), while methysergide (20 mg/kg) and ketanserin (10 mg/kg) demonstrated no
      antagonistic effects. 8-OH-DPAT (0.3 and 1 mg/kg) also showed an inhibiting
      effect on histamine turnover in various regions of rat brains. Although the
      extent of inhibition was slightly larger in the striatum and cerebral cortex,
      there was no marked regional difference. These results suggest that histaminergic
      activity in the brain is regulated by 5-HT1A receptors.

PMID- 1388248
TI  - Endocrine status in stage II vs. advanced premenopausal and postmenopausal breast
      cancer patients.
AB  - Circulating preoperative levels of DHEA-S, androstenedione and SHBG were measured
      in 40 premenopausal and 49 postmenopausal breast cancer patients, and in 30 and
      15 age-matched healthy controls, respectively. Moreover, the levels of LH, FSH,
      prolactin, estradiol, progesterone, testosterone, DHEA-S, androstenedione and
      SHBG of Stage II breast cancer patients were compared with advanced patients and
      also with controls. In premenopausal patients the levels of steroid hormones were
      significantly low whereas those of peptide hormones were significantly high. On
      the contrary, in postmenopausal patients, except DHEA-S, all other hormones were
      significantly elevated in comparison with controls. In premenopausal patients,
      DHEA-S, androstenedione, estradiol, progesterone, and testosterone decreased as
      stage advanced with concomitant increase of SHBG, LH, FSH and prolactin when
      compared with hormone levels of Stage II patients. In postmenopausal advanced
      breast cancer patients, when compared with Stage II patients, the levels of SHBG,
      LH, FSH, and prolactin increased significantly, while DHEA-S, androstenedione,
      estradiol, and progesterone decreased as stage advanced.

PMID- 1388249
TI  - Lipoprotein(a) predicts the risk of thrombogenic complications in nephrotic
      syndrome.

PMID- 1388250
TI  - Influence of long-term amelioration of anemia and blood pressure control on left
      ventricular hypertrophy in hemodialyzed patients.
AB  - The course of left ventricular hypertrophy was investigated in anemic
      hemodialysis patients treated with recombinant human erythropoietin (r-huEPO). 12
      patients, aged 60.8 +/- 9.9 years (mean +/- SD) were treated for 18.8 +/- 2.7
      months. Left ventricular size was estimated by echocardiography performed before
      treatment and at least 12 months after relieving anemia. Patients had signs of
      left ventricular and/or asymmetric septal hypertrophy when compared with a
      nonanemic and normotensive control group matched for sex and age. At baseline,
      hemoglobin (Hb) was 8.6 +/- 0.7 g/dl; interventricular septum thickness (IVST)
      was 1.75 +/- 0.34 cm, left ventricular posterior wall thickness (LVPWT) 1.32 +/-
      0.19 cm, left ventricular muscle mass index (LVMI) 222.7 +/- 41 g/m2 and blood
      pressure (BP) 146.4 +/- 10/81.6 +/- 6 mm Hg. Hb rose to 11.4 +/- 1.2 g/dl (p less
      than 0.001); IVST and LVMI decreased to 1.42 +/- 0.35 cm (p less than 0.02) and
      155.4 +/- 25.1 g/m2 (p less than 0.001); LVPWT and BP remained unchanged (1.30 +/
      0.26 cm and 146.8 +/- 16.9/81.2 +/- 7.8 mm Hg) at the end of the study. During
      the observation period, two groups of 5 and 7 patients differed from each other.
      The group of 5 patients had higher BP values (158.9 +/- 9.8/86.5 +/- 5.3 vs.
      140.0 +/- 9.5/79.2 +/- 6.8 mm Hg, p less than 0.01), and the period with Hb
      values above 10 g/dl was shorter (14.5 +/- 2.4 vs. 17.8 +/- 2.4 months, p less
      than 0.05). These 5 patients failed to show a significant decrease in IVST and
      LVMI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388252
TI  - [Value of computerized tomography in the diagnosis of discopathy in the L4-L5-S1
      segment].
AB  - The aim of this analysis was demonstration of the usefulness of CT in the
      diagnosis of lumbar discopathy. In 110 patients with backache, CT of the L4-L5-S1
      part of the spine was done. The observed abnormalities were analysed, including
      presence of nucleus pulposus herniation, pathological changes of osseous
      structures of the spine, width of the vertebral canal and lateral recesses, and
      presence of other lesions there. Comparing the results of (CT) and myelography
      with intraoperative observations it was possible to confirm the high usefulness
      and value of CT in such cases. CT may be an important diagnostic method
      preoperatively in patients with iodine hypersensitivity and those with vertebral
      canal stenosis.

PMID- 1388251
TI  - Response suppression induced with selective 5-HT agonists can be differentially
      blocked with LY53857 in an animal model of depression.
AB  - Studies from this laboratory have demonstrated that administration of the
      selective 5-HT2/1C antagonist LY53857 can block 5-HTP-induced response
      suppression. To further investigate the serotonergic mechanisms involved in this
      effect, we decided to test the capacity of LY53857 to block response suppression
      induced with two selective 5-HT agonists. After a 15 minute baseline period, rats
      trained to press a lever for milk reinforcement on a VI 1' schedule were given IP
      injections of 1.0 mg/kg DOI, or 1.0 mg/kg 8-OH-DPAT to induce response
      suppression. Subsequently, rats were injected with 1.0 mg/kg LY53857 1 hour prior
      to DOI- or 8-OH-DPAT-induced response suppression. Preinjections with LY53857
      resulted in a 100% blockade of DOI-induced response suppression whereas the same
      dose did not block response suppression induced with 8-OH-DPAT. These results
      indicate that the 5-HTP-induced response suppression shows some pharmacological
      similarity to DOI-induced response suppression and may be mediated through 5-HT2
      and/or 5-HT1C receptors.

PMID- 1388253
TI  - [Factors determining the results of surgical treatment of backache syndromes in
      the lumbar spine].
AB  - The therapeutic results were analysed in a group of 509 patients operated on for
      low back pain syndromes (after previous establishing of indications based on
      clinical examination and radiological investigations) with over 6 months of
      follow-up. The therapeutic results were compared with the observed symptoms and
      signs, neurological findings, age, duration of acute phase of the disease,
      surgical approach used, changes found during the operation, stability of the
      spine and type of its surgical immobilization. The therapeutic result depended
      mainly on the degree of neurological abnormalities before the operation, duration
      of the acute phase and operative findings as well as spinal stability. The
      operative approach and stabilization type, although influencing the result, were
      a consequence of the above factors.

PMID- 1388254
TI  - The effects of rubidium, caesium and quinine on 5-HT-mediated behaviour in rat
      and mouse--3. Quinine.
AB  - It has been shown that caesium, which shares properties with quinine as a K(+)
      channel blocker, enhanced 5-HT-mediated behaviour in both rats and mice. It was
      therefore of interest to investigate the effects of quinine on 5-HT-mediated
      behaviour in the rat and mouse. Quinine, dose-dependently (ED50 = 5 mg/kg),
      produced the 5-HT behavioural syndrome in rats pre-treated with tranylcypromine
      (TCP) (15 mg/kg, i.p.). p-Chlorophenylalanine (i.p., 300 mg/kg x2) or (-)
      propranolol (20 mg/kg, i.p.), pindolol (4 mg/kg, i.p.) and ritanserin (0.4 mg/kg,
      s.c.), all prevented the behavioural syndrome induced by quinine (72 mg/kg, i.p.)
      plus TCP. The administration of quinine (72 mg/kg, i.p.) enhanced the 5-HT
      syndrome elicited by p-chloramphetamine (4 mg/kg, i.p.) and the 5-HT agonists, 8
      OH-DPAT (0.5 mg/kg, s.c.), 5-MeODMT (2 mg/kg, i.p.), DOI (8 mg/kg, s.c.) and
      quipazine (25 mg/kg, i.p.) in rats. Pretreatment with quinine also potentiated
      the 5-HT2-mediated head-twitch in the mouse but had no effect on the hypothermia
      in the mouse, induced by 8-OH-DPAT (0.5 mg/kg, s.c.). Quinine also enhanced the
      rate of synthesis of 5-HT in the brain of the rat. On the basis of these
      findings, together with those in the preceding two papers, it is suggested that
      the effects of rubidium, caesium and quinine, to enhance differentially various
      aspects of 5-HT function are mediated by actions on 5-HT-modulated K(+)-channels.
      This conclusion is also discussed in relation to the actions of lithium and
      electroconvulsive shock on 5-HT function in brain and the treatment of manic
      depressive disease.

PMID- 1388257
TI  - Medical certificates: are they necessary?

PMID- 1388256
TI  - A comparative study of the anatomical, radiological and therapeutic features of
      the lumbar facet joints.
AB  - An anatomical study of the lumbar apophyseal joints was carried out to facilitate
      recognition of facet joint lesions, which we now examine routinely by
      percutaneous arthrography. Special attention was given to the configuration of
      the different compartments of the joint space and to its relationships with the
      contents of the intervertebral foramen. The abnormalities seen on lumbar facet
      joint arthrography are very varied; two major groups should be stressed: synovial
      fringe hypertrophy and pseudodiverticular synovial ectasia. The percutaneous
      approach to lumbar facet joint arthrography allows it to be used a therapeutic
      measure, with injection of anti-inflammatory drugs into the joint space, the
      beneficial effects of which were confirmed in our series. The precision,
      efficiency and cost-effectiveness of this outpatient technique justify and should
      encourage its more widespread application in the diagnosis and treatment of low
      back pain.

PMID- 1388255
TI  - The effects of corticosterone on 5-HT receptor function in rodents.
AB  - In the mouse, administration of corticosterone-21-acetate (30 mg/kg, s.c. daily)
      for 3 and 10 days produced an attenuation of the hypothermic response to the 5
      HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), which
      was not present after administration for 1 day. A similar effect was observed in
      the rat after administration of corticosterone-21-acetate (30 mg/kg, s.c. daily)
      for 10 days. Mice which had been given corticosterone for 10 days displayed the
      serotonin syndrome when injected with 5-hydroxytryptophan (5-HTP, 100 mg/kg,
      s.c.), 15 min after injection of carbidopa (25 mg/kg, i.p.). This was not seen in
      control animals. The serotonin syndrome was also induced in mice using 8-OH-DPAT;
      this increased in a dose-dependent manner and could be significantly decreased by
      pre-treatment with 1-(2-methoxyphenyl)-4-(4-phthalimidobutyl)-piperazine (NAN-190
      5 mg/kg, i.p., 30 min prior to administration of 8-OH-DPAT), a 5-HT1A receptor
      antagonist. Administration of corticosterone (30 mg/kg, s.c. daily) did not
      significantly alter the serotonin syndrome induced in treated mice, compared with
      controls. Mice pre-treated for 3 or 10 days with corticosterone did not differ
      from controls in the number of head-twitches induced by 5-HTP and carbidopa or 5
      methoxy-N,N-dimethyltryptamine, nor did they differ from controls in their
      response to the putative 5-HT1B agonist 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4
      yl)1-H indole (RU 24969, 3 mg/kg, i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388258
TI  - Dangers of hepatitis B vaccine.

PMID- 1388259
TI  - Glucosyltransferase phase variation in Streptococcus gordonii modifies adhesion
      to saliva-coated hydroxyapatite surfaces in a sucrose-independent manner.
AB  - Phase variation of Streptococcus gordonii between high (Spp+) and low (Spp-)
      levels of glucosyltransferase (GTF) activity resulted in the greater adhesion of
      Spp- strains to saliva-coated hydroxyapatite (S-HA) in a washed-cell adhesion
      test. Specific GTF mutants did not show this response. Although washed Spp+ cells
      produced 5-fold or more glucan from sucrose than Spp- cells did under the
      conditions of the adhesion test, sucrose elevated the adhesion of both phenotypes
      to hydroxyapatite (HA) equally, but had no effect on adhesion to S-HA. This
      effect was not sucrose-specific, however, because equimolar amounts of other
      carbohydrates and NaCl elevated adhesion of both Spp types to levels similar to
      those seen with sucrose. Adhesion did not correlate with relative changes in cell
      hydrophobicity. These results suggest that, in addition to changes in GTF
      activity, other changes relevant to adhesion may occur during Spp phase
      variation.

PMID- 1388260
TI  - How can perceptual science help the handicapped?

PMID- 1388261
TI  - Acitretin (Neotigason). A review of pharmacokinetics and teratogenicity and
      hypothesis on metabolic pathways.
AB  - Acitretin was introduced as a replacement for etretinate, the ethyl ester of
      acitretin. Acitretin is eliminated at a much faster rate than etretinate.
      Although both drugs are teratogens, the replacement was important especially as
      it allowed for a much shorter post-medication period in which pregnancy should be
      precluded. Recent findings showed the presence of etretinate in the plasma of
      acitretin-treated patients. This article gives a review of known metabolic
      pathways of the retinoids and tries to elucidate the possible conversion of
      acitretin into etretinate after acitretin ingestion.

PMID- 1388262
TI  - Continuation and maintenance therapy with antidepressive agents. Meta-analysis of
      research (II)

PMID- 1388263
TI  - Renal contraluminal transport systems for organic anions (paraaminohippurate,
      PAH) and organic cations (N1-methyl-nicotinamide, NMeN) do not see the degree of
      substrate ionization.
AB  - Using the stop-flow peritubular capillary microperfusion method pH dependence of
      the interaction of different substrates with the contraluminal PAH- and NMeN
      transporter was investigated. Substrates for both transport systems with pKa
      values around 7.0 were chosen and the pH of the perfusates was varied between 6.0
      and 8.0. The inhibitory potencies (app. Ki values) were determined and the influx
      into the proximal tubular cells was measured. The app. Ki(NMeN) values of
      imidazole (pKa 7.03), a substrate for the NMeN-transporter, the app. KiPAH values
      of the dipeptide tryptophyl-tryptophan (pKa 7.36), a substrate for the PAH
      transporter, and the app. Ki,NMeN and Ki,PAH of cimetidine (pKa 6.98) and
      buspirone (pKa 7.2) which interact with both transport systems, did not vary
      between perfusate pH 6.0 and 8.0. The same holds for the influx of 3H-cimetidine
      into proximal tubular cells. The data indicate that both transporters have no
      preference for the ionized form of their substrates and that the name organic
      anion and organic cation transporter resides rather on history than on molecular
      interaction.

PMID- 1388264
TI  - Viral hepatitis. Preexposure and postexposure prophylaxis.
AB  - Rational strategies for preventing viral hepatitis are being developed as the
      epidemiology of the disease is becoming better defined. A vaccine is available
      only for hepatitis B. Other prophylactic strategies are based on avoidance of
      high-risk behavior and use of immune globulin. Universal vaccination for
      hepatitis B is now recommended.

PMID- 1388265
TI  - [Characteristics of the course of newly diagnosed tuberculosis among socially
      maladapted persons].

PMID- 1388266
TI  - [Organization of prophylactic mass screening for tuberculosis of the population
      in the south of the Aral sea cost region].
AB  - The results of mass prophylactic screening of the population for tuberculosis in
      the south of the Aral sea costal region have been generalized with consideration
      of its geographic and sanitary--epidemiologic conditions. A mixed model of
      comprehensive prophylactic screenings was used for the first time with
      integration, for the first time, of the traditional (team) and field-work
      methods. The obtained results proved the efficiency of this approach: during one
      year a total of 1,217,400 subjects or 80% of the relevant population were
      involved in the prophylactic screening for the first time in one region. As a
      result, the epidemiologic situation related to tuberculosis was revealed and a
      complex of the therapeutic and health-improvement measures accomplished. The
      proposed measures have been tested and made the basis of a section in a complex
      program "Health of the population of the Aral sea costal region up to the 2000th
      year" which is recently being introduced in other regions of the republic.

PMID- 1388267
TI  - [Ecologic significance of M. avium infectiousness of waterside and aquatic
      birds].
AB  - A total of 777 specimens of the river-side and water birds of 36 species
      belonging to 8 orders were examined for infectivity by the causative agent of
      tuberculosis M. avium. Examination was carried out in the northern zone of the
      land along the lower Volga. Infectivity was studied by serologic and
      bacteriologic tests. Serologic examination showed that 104 out of the 399 birds
      were AIT-positive (26.0 +/- 2.195%), in bacteriologic examination 73 out of the
      378 specimens were infected (19.57 +/- 2.040%). The infectivity parameters of
      birds determined by both methods had certain characteristic features typical of
      the examination territory. The character of distribution of the infected birds
      was determined according to the regions of the examination zone.

PMID- 1388268
TI  - Independent deposition of heterogeneous nuclear ribonucleoproteins and small
      nuclear ribonucleoprotein particles at sites of transcription.
AB  - The major nuclear ribonucleoproteins (RNPs) involved in pre-mRNA processing are
      classified in broad terms either as small nuclear RNPs (snRNPs), which are major
      participants in the splicing reaction, or heterogeneous nuclear RNPs (hnRNPs),
      which traditionally have been thought to function in general pre-mRNA packaging.
      We obtained antibodies that recognize these two classes of RNP in Drosophila
      melanogaster. Using a sequential immunostaining technique to compare directly the
      distribution of these RNPs on Drosophila polytene chromosomes, we found that the
      two patterns were very similar qualitatively but not quantitatively, arguing for
      the independent deposition of the two RNP types and supporting a role for hnRNP
      proteins, but not snRNPs, in general transcript packaging.

PMID- 1388269
TI  - A factor from CD8 cells of human immunodeficiency virus-infected patients
      suppresses HLA self-restricted T helper cell responses.
AB  - Defective in vitro T helper cell (Th) function can occur in asymptomatic human
      immunodeficiency virus (HIV)-seropositive (HIV+) individuals. A characteristic,
      early finding is the loss of an in vitro response to recall antigens, such as
      influenza A virus (FLU), despite an intact Th response to alloantigen (ALLO). To
      determine whether suppressor cells and/or inhibitory factors could contribute to
      this HIV-associated Th immunodeficiency, coculture studies were performed using
      peripheral blood leukocytes (PBLs) from monozygotic twins, one of whom was HIV
      infected (HIV+) and one of whom was uninfected (HIV-seronegative, HIV-). In vitro
      Th function was measured as interleukin 2 production or proliferation to FLU and
      ALLO. Two pairs of twins were repetitively studied. A single HIV+ individual with
      multiple samples of cryopreserved PBLs over 6 years (including a HIV- specimen)
      was also studied. PBLs from the HIV+, but not from the HIV-, individuals
      demonstrated defective in vitro Th function in response to FLU but not to ALLO.
      PBLs from HIV+ individuals could induce a similar defect in the Th function of
      syngeneic or autologous HIV- PBLs. This suppression was generated by CD4
      depleted, but not by CD8-depleted, PBLs. A suppressive factor from CD8+ cells of
      HIV+ donors was generated by 24-hr unstimulated cultures of HIV+ PBLs. This
      factor inhibited FLU but not ALLO responses of autologous, syngeneic, or
      allogeneic HIV- PBLs. This suppressive effect could not be explained by HIV
      infection or replication during the culture period. These results demonstrate
      that selective abrogation of Th function to recall antigens in HIV+ individuals
      is associated with an inhibitory factor produced by CD8+ T cells.

PMID- 1388270
TI  - Alternative splicing generates functionally distinct N-methyl-D-aspartate
      receptors.
AB  - We have used expression cloning in Xenopus oocytes to isolate two different cDNAs
      encoding functional N-methyl-D-aspartate (NMDA) receptor subunits. The two
      receptors (NMDA-R1A and -R1B) display different pharmacologic properties as a
      consequence of alternative exon addition within the putative ligand-binding
      domain. The splicing choice is regulated such that R1B is the predominant form of
      receptor in the cerebellum, whereas R1A predominates in other brain regions.
      Expression of either of the subunits alone in oocytes results in an NMDA-evoked
      inward current with electrophysiologic properties closely resembling those of the
      NMDA receptors observed in neurons. Thus, the complex properties exhibited by the
      NMDA receptor in neurons can be generated by the expression of a single receptor
      subunit.

PMID- 1388271
TI  - Cloning and intracellular localization of the U2 small nuclear ribonucleoprotein
      auxiliary factor small subunit.
AB  - U2 small nuclear ribonucleoprotein auxiliary factor (U2AF), an essential
      mammalian splicing factor, is composed of two subunits: a 65-kDa protein
      (U2AF65), which binds the pre-mRNA polypyrimidine tract and is required for in
      vitro splicing, and an associated 35-kDa protein (U2AF35). Here we report the
      isolation of a cDNA encoding U2AF35. U2AF35 contains sequence motifs found in
      several mammalian pre-mRNA splicing factors. We show directly that U2AF65 and
      U2AF35 interact with each other and delineate the regions of both proteins that
      mediate this interaction. Using anti-peptide antibodies against U2AF35, we show
      that the protein has the intracellular distribution characteristic of U2AF65.
      Both U2AF65 and U2AF35 are concentrated in a small number of nuclear foci
      corresponding to coiled bodies, subnuclear organelles first identified by light
      microscopy in 1903.

PMID- 1388272
TI  - Differential response of maize catalases to abscisic acid: Vp1 transcriptional
      activator is not required for abscisic acid-regulated Cat1 expression.
AB  - In this paper we describe the distinctive responses of the maize catalases to the
      plant growth regulator abscisic acid (ABA). We analyzed RNA and enzyme
      accumulation in excised maize embryos and found that each catalase responded
      differently to exogenously applied ABA. Levels of Cat1 transcript and enzyme
      activity rapidly increased. In contrast, levels of Cat2 transcript and protein
      decreased, while Cat3 transcript levels were not affected. In developing kernels
      of the ABA-deficient/biosynthetic viviparous mutant vp5, lower levels of Cat1 RNA
      correlated with lower endogenous ABA levels when compared to measured levels in
      comparably aged wild-type siblings from the same ear. The maize vp1 mutant line
      is morphologically insensitive to normal endogenous levels of ABA. Analysis of
      the response of Cat1 to exogenously applied ABA in mutant and wild-type vp1
      sibling embryos suggests that, unlike other ABA-responsive genes analyzed to
      date, the Vp1 gene product is not essential for the ABA-mediated regulation of
      Cat1. The significance of these responses to ABA in defining the roles of the
      various CATs in maize is discussed.

PMID- 1388273
TI  - Cardiorenal reflexes do not attenuate the renal effects of infused atriopeptin in
      conscious dogs.
AB  - Low-dose infusions of atriopeptin produce only a modest diuresis and natriuresis.
      However, these infusions also decrease atrial pressures, a change that has been
      postulated to elicit an antidiuretic and antinatriuretic reflex from cardiac
      receptors and thereby to attenuate the direct renal effects of atriopeptin. To
      determine whether the renal effects of intravenously administered atriopeptin
      might be attenuated by a cardiorenal reflex, we infused alpha-human atrial
      natriuretic peptide (alpha-hANP) into cardiac-denervated and sham-operated
      (normal) conscious dogs. Following a control period, alpha-hANP was infused into
      each dog at 12.5, 25, or 50 ng.kg-1.min-1 for 1 hr. Infusion of alpha-hANP at 50
      ng.kg-1.min-1 produced similar decreases in left atrial pressure in both normal
      and cardiac-denervated dogs (peak changes, -1.6 +/- 0.8 vs -2.4 +/- 0.9 mm Hg,
      respectively). Increases in urine flow (peak changes, 0.13 +/- 0.05 vs 0.20 +/-
      0.06 ml/min) and sodium excretion (peak changes, 56 +/- 22 vs 70 +/- 11
      microEq/min) also were not different between groups. The lower doses of alpha
      hANP also elicited renal and hemodynamic responses in the cardiac-denervated dogs
      that did not differ significantly from those in the normal dogs. These data
      indicate that the diuresis and natriuresis elicited by intravenously administered
      alpha-hANP are not attenuated by a cardiorenal reflex in conscious dogs.

PMID- 1388274
TI  - Progestin and estrogen control of cathepsin D expression and processing in rat
      uterine luminal epithelium and stroma-myometrium.
AB  - Progestins increase the activity and rate of synthesis of cathepsin D, a
      lysosomal aspartyl protease, in the uterine luminal epithelium in ovariectomized
      rats. Western blot analysis of luminal epithelial proteins determined that the
      progestin, medroxyprogesterone acetate (MPA) increased the 43-kDa form of
      cathepsin D by 7-fold in 24 hr, whereas estradiol increased the amount of the
      same form by only 2-fold. To examine the precursor-product relationship between
      cathepsin D proteins in the luminal epithelium and stroma-myometrium after
      progestin or estradiol treatment, uterine proteins were prelabeled by incubation
      with [35S]methionine in vitro, cathepsin D was isolated by immunoprecipitation,
      and equal amounts of labeled cathepsin D were subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. After each hormonal treatment in each uterine
      tissue, a 48-kDa precursor was processed into a 44-kDa cathepsin D product.
      Endoglycosidase H digestion of [35S]methionine-labeled cathepsin D from the
      luminal epithelium and stroma-myometrium of medroxyprogesterone-treated rats
      shifted the molecular masses of the cathepsin D proteins by approximately 5.7
      kDa. To examine the contribution of increased mRNA to increased rates of
      cathepsin D synthesis, we measured levels of cathepsin D mRNA in uterine tissues
      after progestin and estrogen treatment. Total RNA was isolated from the uterine
      luminal epithelium and from the stroma-myometrium. Northern blot analysis
      identified a single 2.2-kb RNA band corresponding to the size expected for
      cathepsin D mRNA. Medroxyprogesterone increased levels of cathepsin D mRNA in the
      luminal epithelium (greater than 17-fold) and in the stroma myometrium (3-fold),
      with maximum increases at 9 hr after treatment. Estradiol also increased
      cathepsin D mRNA levels in both uterine tissues, but by only 2-fold. No hormonal
      effects on liver cathepsin D mRNA were observed. Increases in cathepsin D
      synthesis and activity in uterine tissues in response to progestin and estrogen
      appear to depend in part upon increased levels of mRNA.

PMID- 1388275
TI  - Reinforced responding of the 11-day-old rat pup: synergistic interaction of D1
      and D2 dopamine receptors.
AB  - Reinforced responding of 11-day-old rat pups was assessed after blockade of D1
      and D2 dopamine receptors. Initially, rat pups were trained to traverse a
      straight alley for nipple attachment reward. Rat pups were than injected IP with
      either the D1 antagonist SCH 23390 (0.01, 0.015, 0.03, or 0.1 mg/kg), the D2
      antagonist sulpiride (15 or 50 mg/kg), or a combination of SCH 23390 (0.015
      mg/kg) and sulpiride (15 mg/kg). The approach performance of drug-treated pups
      was then compared to vehicle-treated pups on both reinforcement and extinction
      trials. Sulpiride (15 mg/kg) did not affect either the extinction or reinforced
      responding of 11-day-old rat pups. In contrast, SCH 23390-treated pups showed
      significantly longer response latencies than the vehicle controls in both
      extinction and reinforcement conditions. Combined treatment with SCH 23390 and
      sulpiride produced the longest response latencies. Analyses of "best score" and
      frequency data indicated that the drug-induced decline in responding was due to
      effects on both reward processes and motor capability. The combined results
      indicate that D1 and D2 receptors interact complexly to affect reinforced
      responding.

PMID- 1388276
TI  - Influence of dopaminergic and serotonergic neurons on intravenous ethanol self
      administration in the rat.
AB  - Rats implanted with chronic indwelling intravenous catheters and allowed access
      to a self-administration apparatus learned to self-inject intravenous ethanol.
      Ethanol concentrations of 0.5, 1.0, and 2.0%, corresponding to a dose/injection
      of 1, 2, and 4 mg/kg, respectively, were consistently self-injected. Self
      injection was not acquired or maintained with ethanol doses of 0.5 or 8
      mg/kg/injection. Saline replacement of ethanol reservoirs led to marked increases
      in lever-pressing response in animals self-injecting 1, 2, and 4 mg/kg
      ethanol/injection but not with 0.5 or 8 mg/kg/injection. Neurotoxin-induced
      lesions of dopamine-(DA) containing neurons in nucleus accumbens septi failed to
      alter the acquisition or maintenance of ethanol self-injection. Pretreatment with
      haloperidol (0.05 and 0.1 mg/kg, SC) failed to alter hourly or daily self
      injection rates. On the other hand, p-chlorophenylalanine pretreatment increased,
      while fluoxetine (2.5 and 5.0 mg/kg) administration significantly reduced, self
      injected intravenous ethanol. These data suggest that ethanol is self-injected by
      the rat in a narrow dose range and that 5-hydroxytryptamine (5-HT), but not DA
      containing neurons, subserves some function in the reinforcing or aversive
      affects of ethanol.

PMID- 1388277
TI  - Domestication alters 5-HT1A receptor binding in rat brain.
AB  - Serotonin-1A receptor binding density was compared in the brains of wild and
      domesticated adult male Rattus norvegicus using in vitro receptor autoradiography
      of [3H]8-hydroxy-2-[n-dipropylamino]tetraline (DPAT). While both groups exhibited
      similar patterns of labeling, [3H]DPAT binding density was significantly (p less
      than or equal to 0.05) lower in the median raphe nucleus and greater in
      superficial entorhinal cortex and rostral dentate gyrus of domesticated compared
      to wild rats. The results suggest that specific serotonergic circuits from the
      median raphe nucleus to the entorhinal and hippocampal regions might be involved
      in regulation of the defensive behaviors that differ profoundly between wild and
      domesticated rats. The relationship of these putative differences to behavioral
      disorders such as anxiety and depression in humans is discussed.

PMID- 1388278
TI  - The 5-HT1A antagonist (-)-alprenolol fails to modify sleep or zimeldine-induced
      sleep-waking effects in rats.
AB  - Sleep and waking in rats were studied for 8 h following administration of a
      selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a putative 5
      HT1A antagonist (L(-)-alprenolol hydrogene tartrate monohydrate [(-)-alprenolol])
      and a combination of (-)-alprenolol and zimeldine. Consistent with earlier
      findings, zimeldine gave a biphasic effect on sleep and waking. Waking was
      increased during the first 3 h, followed by a small decrease. Deep slow-wave
      sleep (SWS-2) showed the opposite trend. An initial decrease in SWS-2 was
      followed by an increase after around 3 h. Rapid eye movement sleep was markedly
      suppressed and latencies to sleep increased after zimeldine. (-)-Alprenolol had
      no effects on the different sleep and waking stages or latencies to sleep. The 5
      HT1A antagonist also failed to modify the effects of zimeldine administration.
      The behavioral syndrome induced by a selective 5-HT1A agonist [8-hydroxy-2-(di-n
      propyl-amino)-tetralin (8-OH-DPAT)] was clearly antagonized by administration of
      (-)-alprenolol, indicating that (-)-alprenolol was an efficient 5-HT1A blocker.
      The data indicate that the sleep-waking effects of zimeldine cannot easily be
      explained by stimulation of 5-HT1A receptors.

PMID- 1388279
TI  - Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the
      marmoset.
AB  - The cognitive-enhancing potential of the 5-hydroxytryptamine (5-HT) selective 5
      HT3 receptor antagonist, ondansetron, was investigated in a model of cognitive
      impairment induced by the muscarinic receptor antagonist, scopolamine. For this
      purpose, marmosets were trained in an object discrimination task utilizing the
      Wisconsin General Test Apparatus. Administration of scopolamine (0.01-0.04 mg/kg,
      SC) caused a dose-dependent impairment in the acquisition of the object
      discrimination task in that marmosets required more trials to reach criterion,
      made more errors, and took longer to choose the objects. Administration of
      arecoline (0.06-0.1 mg/kg, SC) or 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H
      imidazol- 1-yl)methyl]-4H-carbazol-4-one,HCl.2H2O (ondansetron) (0.1-1
      micrograms/kg, SC) prevented the scopolamine-induced impairment in task
      acquisition in that the performance of marmosets was indistinguishable from that
      of saline-treated animals and was significantly better than that following
      scopolamine/saline. From these studies, we conclude that ondansetron prevents
      impairment in the cognitive performance of marmosets induced by administration of
      scopolamine.

PMID- 1388280
TI  - Sex differences in self-disclosure: a meta-analysis.
AB  - A meta-analysis of 205 studies involving 23,702 Ss was conducted to determine
      whether there are sex differences in self-disclosure. Across these studies, women
      disclosed slightly more than men (d = .18). This effect size was not homogeneous
      across studies. Several moderator variables were found. Sex of target and the
      interaction effect of relationship to target and measure of self-disclosure
      moderated the effect of sex on self-disclosure. Sex differences in self
      disclosure were significantly greater to female and same-sex partners than to
      opposite-sex or male partners. When the target had a relationship with the
      discloser (i.e., friend, parent, or spouse), women disclosed more than men
      regardless of whether self-disclosure was measured by self-report or observation.
      When the target was a stranger, men reported that they disclosed similarly to
      women; however, studies using observational measures of self-disclosure found
      that women disclosed more than men.

PMID- 1388281
TI  - Gender differences in mate selection preferences: a test of the parental
      investment model.
AB  - Evolutionary-related hypotheses about gender differences in mate selection
      preferences were derived from Triver's parental investment model, which contends
      that women are more likely than men to seek a mate who possesses nonphysical
      characteristics that maximize the survival or reproductive prospects of their
      offspring, and were examined in a meta-analysis of mate selection research
      (questionnaire studies, analyses of personal advertisements). As predicted, women
      accorded more weight than men to socioeconomic status, ambitiousness, character,
      and intelligence, and the largest gender differences were observed for cues to
      resource acquisition (status, ambitiousness). Also as predicted, gender
      differences were not found in preferences for characteristics unrelated to
      progeny survival (sense of humor, "personality"). Where valid comparisons could
      be made, the findings were generally invariant across generations, cultures, and
      research paradigms.

PMID- 1388282
TI  - MMPI-ER two-point codes of industrially injured Hispanic workers by DSM-III--R
      diagnosis.
AB  - The purpose of this study was to describe the MMPI-ER two-point codes of 492
      Hispanic adults who had sustained work-related injuries and who had applied for
      workers' compensation benefits. More specifically, the focus was on whether there
      are unique MMPI two-point codes for Hispanic workers with three specific types of
      DSM-III--R diagnoses--adjustment disorder, anxiety disorder, and major
      depression. Analysis suggests that psychiatric condition or diagnosis may act as
      a moderator variable in Hispanic persons' MMPI performance, including MMPI two
      point codes.

PMID- 1388283
TI  - [Basic and clinical aspects of human hepatocyte growth factor].

PMID- 1388284
TI  - [Laparoscopic cholecystectomy. The beginning of a new era].
AB  - An important breakthrough in the field of general surgery, laparoscopic
      cholecystectomy (LC) offers significant advantages for patients. Major reasons
      for the rapid worldwide acceptance of this new surgical procedure is that
      patients experience reduced postoperative pain, ileus is virtually abolished, and
      the patient is able to leave the hospital the following day without a major
      abdominal scar. This appears to respond to patients' desire for less invasive
      approaches to the treatment of gallstone disease. LC is thus becoming the
      treatment of choice for symptomatic gallbladder disease. Its rapidly growing
      popularity is evident in Italy where many centers are offering LC routinely, in
      alternative to open cholecystectomy. A critical appraisal of this new technology
      is necessary, in light of recent data from centers presenting results and
      complications of large series of LCs. Adequate training of surgeons who will
      perform LC is also becoming a major concern. In this review the authors describe
      patient evaluation and selection for LC. Effective therapeutic strategies are
      illustrated, including the central, but nevertheless controversial role of
      endoscopic retrograde cholangiopancreatography (ERCP) as an approach to common
      bile duct lithiasis. Currently, LC should be performed in centers with the
      availability of an endoscopist with expertise in ERCP. Following the success of
      LC, other minimally invasive techniques will evolve in various surgical
      specialties. New generations of surgeons will thus have to familiarize with these
      emerging techniques while maintaining a critical attitude of evaluation.

PMID- 1388285
TI  - [A case of phlebothrombosis of lower extremity and pulmonary embolism due to
      progesterone].
AB  - A case with lower extremity phlebothrombosis and pulmonary embolism caused by
      progesterone is reported in this paper. The patient is a 64-year-old woman who
      had been operated on for right breast cancer 22 years before. It was noticed that
      there was a relapsing cancer on her right shoulder 6 months before this episode.
      After effective treatment of 5-FU, she had received 1,200mg of
      Medroxyprogesterone acetate and 30mg of Tamoxifen daily for 4 months. With the
      complaint of dyspnea and left leg swelling 4 months after above treatment, she
      was admitted in our hospital. Laboratory data and angiograms showed venous
      thrombosis in her left leg and pulmonary embolism. Relapsing cancer had already
      disappeared by the time she was admitted. After discontinuance of these
      medicines, her condition had improved. Considering these observations, the
      patient's phlebothrombosis and embolism seem to have been caused by
      Medroxyprogesterone acetate.

PMID- 1388286
TI  - Estimating genomic distance from DNA sequence location in cell nuclei by a random
      walk model.
AB  - The folding of chromatin in interphase cell nuclei was studied by fluorescent in
      situ sequences chromatin according to a random walk model. This model provides
      the basis for calculating the spacing of sequences along the linear DNA molecule
      from interphase distance measurements. An interphase mapping strategy based on
      this model was tested with 13 probes from a 4-megabase pair (Mbp) region of
      chromosome 4 containing the Huntington disease locus. The results confirmed the
      locations of the probes and showed that the remaining gap in the published maps
      of this region is negligible in size. Interphase distance measurements should
      facilitate construction of chromosome maps with an average marker density of one
      per 100 kbp, approximately ten times greater than that achieved by hybridization
      to metaphase chromosome. achieved by hybridization to metaphase chromosomes.

PMID- 1388287
TI  - Threshold phenomena and long-distance activation of transcription by RNA
      polymerase II.
AB  - To explore the underlying mechanisms by which genes are regulated in eukaryotes,
      long-distance transcriptional activation and threshold effects were reconstituted
      in vitro. Long-range activation of transcription by GAL4-VP16 protein located
      1300 base pairs upstream of the RNA start site was dependent on packaging of the
      template into histone H1-containing chromatin. A transcriptional threshold effect
      by GAL4-VP16 was observed with repressed chromatin templates but not naked DNA
      templates. The experimental data with the chromatin templates were similar to the
      theoretical activation profile that is predicted if the action of each DNA bound
      protomer of GAL4-VP16 were independent and additive in terms of free energy.

PMID- 1388288
TI  - Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the
      human cell cycle.
AB  - Human cyclin E, originally identified on the basis of its ability to function as
      a G1 cyclin in budding yeast, associated with a cell cycle-regulated protein
      kinase in human cells. The cyclin E-associated kinase activity peaked during G1,
      before the appearance of cyclin A, and was diminished during exit from the cell
      cycle after differentiation or serum withdrawal. The major cyclin E-associated
      kinase in human cells was Cdk2 (cyclin-dependent kinase 2). The abundance of the
      cyclin E protein and the cyclin E-Cdk2 complex was maximal in G1 cells. These
      results provide further evidence that in all eukaryotes assembly of a cyclin-Cdk
      complex is an important step in the biochemical pathway that controls cell
      proliferation during G1.

PMID- 1388290
TI  - [Initial experience with laparoscopic cholecystectomy].
AB  - The authors present their first experiences with laparoscopic cholecystectomy.
      They introduced this new operative method in Czechoslovakia. They operated upon
      58 patients. The authors discuss about indication, complications and results.

PMID- 1388289
TI  - [Initial experience with laparoscopic cholecystectomy].
AB  - The authors discuss the technique and indications for laparoscopic
      cholecystectomy. n the course of four and a half months they operated, using this
      technique, 74 patients, in two patients they had to switch over to open
      cholecystectomy. They did not perform peroperative biligraphy. Complications
      occurred twice, once an injured ductus choledochus, once a biliary fistula. The
      mean period of hospitalization was 4.7 days. Advantages of the procedure are
      minimal surgical trauma, less intense postoperative pain, a shorter
      hospitalization period, rapid convalescence.

PMID- 1388291
TI  - [Two years of experience and 119 peritoneal dialysis catheters placed with
      peritoneoscopy control and Y-TEC system].
AB  - In this work we report our 24 months experience in the placement of 119
      peritoneal catheters in 105 patients (59 males, 46 females, mean age 60.1 years;
      range 24-90) using the peritoneoscopic insertion technique. After catheter
      implantation a dialysis solution leak is encountered in 7.5% of cases, tunnel
      infection in 4 cases (3.3%) and exit site infection in 12.5% of the catheters.
      Placement by endoscopic control is considered as a technique able to avoid
      catheter migration; in our series we reported this complication in 15 cases
      (12.5%). The easy access to the peritoneal cavity and the atraumatic insertion of
      the catheter obtained with the Y-TEC procedure reduced the hospitalization period
      from 25 to 5 days on average. In our experience actuarial survival of catheters
      is 82.5% at 24 months.

PMID- 1388292
TI  - Training, credentialing, and evaluation in laparoscopic surgery.
AB  - Laparoscopic cholecystectomy has become the procedure of choice for the treatment
      of gallbladder disease. Many general surgeons have incorporated laparoscopic
      cholecystectomy into their clinical practices, usually after completing a
      postgraduate didactic and laboratory animal training course. This additional
      formal training is both appropriate and necessary because laparoscopic surgery
      involves techniques different from those of traditional celiotomy, and most
      surgeons who completed their residencies prior to 1992 have had no laparoscopic
      training. Because additional formal training for practicing surgeons is necessary
      at this time, it is appropriate for hospitals to mandate separate granting of
      operative privileges for laparoscopic surgical procedures. In the near future,
      when graduates of general surgery residency programs have had training in
      laparoscopic surgery, separate privileges will no longer be necessary, and
      laparoscopic procedures should be included in the standard privilege category of
      biliary tract surgery. Once privileges in laparoscopic surgery are granted,
      laparoscopic operations, like all surgical procedures, should be monitored by
      peer review to ensure that they continue to be performed safely and
      appropriately. Only those laparoscopic procedures that are similar to open
      operations and have been shown by pilot studies to be safe (e.g.,
      cholecystectomy) should be included currently in a surgeon's laparoscopic
      privileges. Laparoscopic procedures that are very different from proven open
      procedures and are investigational (e.g., inguinal herniorrhaphy) should be
      permitted by the hospital only as part of an experimental protocol monitored by
      an institutional review board. Only after their safety and efficacy have been
      established should they become part of standard privilege categories.

PMID- 1388293
TI  - Anesthesia for laparoscopic surgery.
AB  - The anesthesiologist's goals during laparoscopic surgery are hemodynamic and
      respiratory stability, appropriate muscle relaxation, control of diaphragmatic
      excursion, intraoperative and postoperative patient analgesia, and a quick
      postanesthesia recovery. One must also consider that 3% to 5% of all laparoscopic
      procedures require conversion to an open laparotomy. Whatever the choice of
      anesthetic technique, it is important to maintain cooperation and communication
      among the members of the operating room team in order to ensure a successful
      patient outcome.

PMID- 1388294
TI  - Laparoscopic instrumentation, videoimaging, and equipment disinfection and
      sterilization.
AB  - Laparoscopic equipment, like the field of laparoscopic surgery, continues to
      evolve rapidly. This article discusses basic laparoscopic equipment and
      instruments now being developed as well as the basics of videoimaging. The topic
      of sterilization and disinfection of laparoscopic equipment is presented in
      detail.

PMID- 1388295
TI  - Diagnostic laparoscopy in nonmalignant disease.
AB  - Laparoscopy is useful in the management of a wide range of benign conditions. In
      the elective situation, it may be chosen to evaluate hepatobiliary disorders,
      abdominal masses, or chronic pain, and is an ideal way to sample tissue. Under
      the emergency setting, it is another tool for the assessment of trauma patients
      and may be of value in those patients with abdominal pain, mesenteric ischemia,
      fever of unknown origin, or gastrointestinal hemorrhage. It is important for the
      surgeon to be familiar with the technique, correctly prepare the patient, and be
      aware of the risks and limitations of this diagnostic modality.

PMID- 1388296
TI  - Laparoscopic management of acute and chronic cholecystitis.
AB  - Contrary to earlier predictions, it appears that acute cholecystitis should be
      considered a relative rather than an absolute contraindication to laparoscopic
      surgery. The most important parameter in determining the feasibility of
      attempting laparoscopic cholecystectomy in the setting of acute inflammation
      appears to be the experience of the surgeon. This also appears to be true when
      encountering individuals with elements of long-standing chronic cholecystitis.
      Although laparoscopic intervention in such patients is associated with a greater
      likelihood of conversion to open laparotomy, the incidence of major biliary and
      nonbiliary complications appears to be low. In addition, these patients enjoy the
      same benefits of laparoscopic surgery as those undergoing elective surgery.

PMID- 1388297
TI  - Biliary ductal anatomy and anomalies. The role of intraoperative cholangiography
      during laparoscopic cholecystectomy.
AB  - Biliary ductal anomalies of surgical importance can occur in 10% of patients. The
      short cystic duct draining into the common bile or right hepatic duct and the
      extreme proximity of the common bile duct in case of spiral or posterior entry of
      the cystic duct--if not recognized in time--can result in ductal injuries. The
      new mobile, digitized fluoroscopic units provide a vastly improved image within
      minutes. In case of an inadvertent ductal injury (extravasation, no contrast
      material visible in the proximal ductal system) the surgeon can immediately
      repair the injury. Routine intraoperative cholangiography is strongly recommended
      during laparoscopic cholecystectomies.

PMID- 1388298
TI  - Laparoscopic management of bile duct stones.
AB  - Although it may seem that laparoscopic cholecystectomy has revolutionized the way
      we approach the patient with stones in the gallbladder and bile ducts, only a few
      rules have really changed. Fluoroscopic cholangiography, a requirement for
      radiologists and gastroenterologists performing percutaneous transhepatic
      cholangiography and ERCP, is slowly finding its way into the operating room. No
      longer is a "palpable stone" a common indication for common bile duct
      exploration. Most importantly, it is not necessary to make an incision into the
      bile duct to remove the majority of bile duct stones. The transcystic approach
      will clear the duct in 85% to 90% of all patients, sparing them extra
      hospitalization, a T-tube, and the risk of creating a bile duct stricture during
      sutured closure of the choledochotomy.

PMID- 1388299
TI  - Alternative methods in the management of bile duct stones.
AB  - Common bile duct stones may now be dealt with, in most cases, without the need
      for surgery. To be sure, surgery continues to remain the gold standard for duct
      clearance and treatment of biliary sepsis. Improvements in endoscopic and
      radiologic technology and methodology have permitted excellent access to the
      biliary tree by the transduodenal and transhepatic approaches. In the majority of
      patients, total duct clearance and excellent drainage can be accomplished,
      averting sepsis and the need for open surgery.

PMID- 1388300
TI  - Laparoscopic herniorrhaphy.
AB  - Laparoscopic inguinal hernia repair could represent an attractive alternative to
      conventional inguinal herniorrhaphy if it can be shown to result in less
      perioperative morbidity (primarily postoperative pain) or a decreased long-term
      recurrence rate. The data addressing either of these concerns will be forthcoming
      in ensuing years. The variations in the laparoscopic approach to the
      preperitoneal space and the differences in dissection and fixation techniques
      outlined in this article reflect the fact that the procedure is still evolving,
      and there is not yet a consensus on the best laparoscopic herniorrhaphy. It is
      likely that there will not be one laparoscopic technique applicable to all
      inguinal hernias. Rather, the patient's body habitus and the type of hernia
      encountered at laparoscopy will persuade the surgeon to use one of several
      techniques. Once a consensus is reached among surgeons as to the optimal
      laparoscopic hernia repair(s), it will be possible to begin gathering data
      concerning perioperative morbidity and recurrence rates. Only then can the
      question be answered whether laparoscopic inguinal herniorrhaphy has any
      advantages over the conventional extraperitoneal operation. A multicenter
      prospective nonrandomized trial has been initiated by our group in an attempt to
      determine whether laparoscopic inguinal herniorrhaphy has efficacy. The exact
      technique employed by the individual centers has not been strictly regulated, but
      general guidelines have been given. It is hoped that this project will provide
      information on whether laparoscopic inguinal herniorrhaphy is a useful
      alternative to conventional repair. Most of the laparoscopic inguinal
      herniorrhaphy techniques described in this article expose the patients to the
      inherent risks of initial laparoscopic penetration of the abdomen and the long
      term possibility of adhesions to the sites where the peritoneum has been
      breached. Because these risks are not present in a conventional repair, the
      laparoscopic technique must have other advantages if it truly is to obtain a
      place in the armamentarium of general surgeons.

PMID- 1388301
TI  - Laparoscopy in malignant disease.
AB  - The use of laparoscopy in patients with malignant disease is particularly helpful
      diagnostically and will often impact on future therapy. The indications and
      complications of this technique in combination with other diagnostic and
      therapeutic modalities in patients with malignant disease are evaluated and the
      accuracy of results are compared to laparotomy procedures. Future trends in
      laparoscopic surgery also are discussed.

PMID- 1388302
TI  - Suturing and knot tying in laparoscopy.
AB  - Laparoscopic surgery is evolving, and its applications are growing to include
      most abdominal operations. Tissue approximation by means other than mechanical
      clips or staples will be increasingly important. Laparoscopic surgeons must learn
      and apply basic suturing and knot-tying skills in this remote, two-dimensional
      operating theater. The authors advocate practice of these skills using inanimate
      and animate training models prior to application in the clinical setting.

PMID- 1388303
TI  - Laparoscopic repair of duodenal ulcer and gastroesophageal reflux.
AB  - The low morbidity and early recovery associated with laparoscopic procedures have
      heralded a new era for many types of surgery. In addition to the initial
      promising reports for duodenal ulcer disease and gastroesophageal reflux
      discussed above, there is a growing body of reports of gastric procedures
      performed laparoscopically, including omentopexy for perforated duodenal ulcer
      and laparoscopic repair of full-thickness stomach injury. Laws et al recently
      described the use of transthoracic vagotomy in recurrent peptic ulcer disease for
      four patients who had previously undergone a gastric drainage procedure. As with
      any new procedure, laparoscopic techniques for duodenal ulcer and Nissen
      fundoplication reviewed in this section need to be evaluated further for long
      term effectiveness and comparability to existing therapy. At least one controlled
      multicenter trial is ongoing to compare the long-term results and cost
      effectiveness of laparoscopic surgery for duodenal ulcer with those of standard
      medical therapy, and as surgeons gain more experience with these laparoscopic
      procedures, it is likely that other similar trials will be initiated.

PMID- 1388304
TI  - Laparoscopic management of the acute abdomen, appendix, and small and large
      bowel.
AB  - The application of laparoscopy for diagnosis and treatment of the acute abdomen,
      appendicitis, and in the management of small and large bowel diseases is a
      natural step for the general surgeon. Acute appendicitis is a common general
      surgical problem that can be difficult to diagnose. Laparoscopy is an excellent
      aid in diagnosis and laparoscopic appendectomy can be performed easily. The
      controversy of incidental appendectomy and recommendations for management are
      discussed. Small and large bowel diseases and their surgical treatment now can be
      managed laparoscopically thus decreasing morbidity and mortality. The uses and
      limitations of these techniques are discussed as well as future trends in
      treatment.

PMID- 1388305
TI  - History of laparoscopic surgery.
AB  - Laparoscopic surgery has a long and colorful history. Although most general
      surgeons, especially in the United States, have discovered this technology only
      recently with the advent of videolaparoscopy, extensive diagnostic and
      therapeutic laparoscopy has been accomplished throughout the twentieth century,
      especially in Europe. Since its origin in 1901 by Kelling to the development of
      the computer chip television camera in the late 1980s, the history of laparoscopy
      entails a chronicle of discovery, innovation, and rediscovery. An appreciation
      for this historical chronicle may actually provide surgeons with a secure
      foundation as they embark on the new era of videolaparoscopy.

PMID- 1388306
TI  - Laparoscopy for the general surgeon.

PMID- 1388307
TI  - Active and passive modulation of cutaneous red cell flux as measured by laser
      Doppler anemometry.
AB  - 1) We have found that the fluctuations in blood motion and blood content in
      cutaneous microvessels in man can be related to either active vasomotion (an
      order parameter for this system) or to a passive penetration of arterial (or
      venous, not shown) pressure waves (the control parameters for the microvascular
      blood motion). Arterial, respiratory (not shown), neuronal and myogenic rhythms
      can be clearly differentiated. 2) Spectral analysis of the signal fluctuations of
      a LDA method (monitoring phasic shifts in blood velocity) in combination with a
      photoplethysmographic method (monitoring shifts in blood content) can be used to
      identify the "normal state". In normal human subjects, it is characterized by
      broad band synergetic liberty (a wide spectrum of rhythmic activities between
      0.01 and 5 Hz). The spectrum readily responds to changes in thermoregulatory
      state and/or myogenic activation by positional changes of the extremity. 3) The
      spectral analysis of LDA and photoplethysmographic records of the volar finger
      reveals predominance of active vasoconstriction during heat conserving
      thermoregulatory reflexes (18 degrees C ambient), predominantly passive reactions
      are seen at 27 degrees C. At 21-24 degrees C ("thermoregulatory indifference
      temperature range"), a mixed reaction pattern is seen. 4) Functional or
      irreversible elimination of the activity of subsystems leads to the elimination
      of circumscript spectral bands and/or potentiation of others. The functional
      differentiation of active and passive components can be utilized in the future
      for differential diagnosis of vascular and nervous disease state on the basis of
      spectral shifts and/or spectral narrowing.

PMID- 1388308
TI  - [Geographic occurrence of retinoblastoma].
AB  - The dot mapping technique was used to study the areas of retinoblastoma
      prevalence in Kazakhstan. A total of 344 retinoblastoma cases were analyzed. The
      landscape confinement of retinal tumors was taken into consideration. The tumors
      were more often seen in the children living near water, near the Alatau plain
      where chemical elements are accumulated, and in large industrial cities polluted
      by industrial waste products. The data of this study will be used to develop
      prophylactic measures and for early detection of retinoblastomas in children
      living in Kazakhstan.

PMID- 1388309
TI  - Transcription mapping of mouse adenovirus type 1 early region 4.
AB  - Early region 4 (E4) of mouse adenovirus type 1 was analyzed by Northern blotting,
      cDNA sequencing, and S1 nuclease protection and primer extension assays. The
      transcription map of this region was dissimilar to the consensus human adenovirus
      E4 transcription map in which all transcripts have identical 5' and 3'-terminal
      sequences. Seven classes of mouse adenovirus type 1 mRNAs were identified; all
      shared the same 3' end. Three classes of unspliced mRNAs differed at their 5'
      start sites, two classes of spliced transcripts differed in the locations of
      their splice acceptors, and two classes of spliced messages differed in their
      splice donors and acceptors. From the structure of the various transcripts,
      translational products were predicted. In addition to a predicted polypeptide
      with similarity to the human adenovirus 2 E4 34K protein previously identified
      (A. O. Ball, C. W. Beard, P. Villegas, and K. R. Spindler, 1991, Virology 180,
      257-265), two open reading frames with similarity to human adenovirus 2 E4 open
      reading frames 2 and 3 were found.

PMID- 1388311
TI  - [Changes in hypertrophy and diastolic left ventricular function during
      hypertension therapy].
AB  - The authors examined a group of hitherto not treated patients with primary
      hypertension and hypertrophy of the left ventricle. By means of echocardiography
      and isometric loading they investigated the effect of treatment on the left
      ventricular morphology and function. Despite long-term normalization of casual
      and loading values of the blood pressure the authors did not observe a
      significant regression of LV hypertrophy. The authors did not find a relationship
      between the casual blood pressure and weight of the left ventricle with exception
      of the diastolic pressure after a load. The indicators of diastolic function did
      not correlate with the weight of the left ventricle but with changes of the end
      diastolic volume and blood pressure.

PMID- 1388310
TI  - In vitro excision and replication of 5' telomeres of minute virus of mice DNA
      from cloned palindromic concatemer junctions.
AB  - HeLa cell extracts containing wild-type copies of the minute virus of mice NS-1
      polypeptide produced from a recombinant vaccinia virus vector could support the
      excision and replication of viral 5' telomeres from cloned concatemer junction
      fragments. Resolution did not occur if wild-type NS-1 was omitted from the
      extract or if the substrate DNA contained palindromic sequences without specific
      viral resolution sites. In the presence of NS-1, [32P]dGTP incorporation into all
      templates was slightly increased, but if the template contained specific viral
      resolution sites DNA synthesis was greatly enhanced, and took two distinct forms:
      (i) generation of a limited number of high-molecular-weight molecules, probably
      due to a form of rolling-circle replication, and (ii) synthesis of new DNA at the
      viral telomeres. Resolution of the junction fragment generated two newly
      synthesized viral telomeres, each of which was covalently associated with NS-1
      and contained a duplex copy of the complex palindrome located around the axis of
      symmetry of the concatemer junction. Cloned junction fragments of 296 bp or more
      could be resolved efficiently in vitro, and since NS-1 molecules were left
      covalently attached to the newly resolved termini, the latter could be partially
      purified by immuno-precipitation with anti-NS-1 serum. Restriction analysis and
      further fractionation of the precipitated DNA showed that the in vitro resolution
      sites were in the predicted positions on either side of the axis of symmetry, and
      that de novo DNA synthesis was associated predominantly with one of the two
      daughter strands. Telomeres were generated from both arms of the substrate with
      equal efficiency, and contained the characteristic "flip" and "flop" sequence
      inversions observed in vivo. Since a high proportion of termini were associated
      with adjacent viral sequences that retained the bacterial methylation pattern, in
      vitro resolution was not dependent upon prior DNA replication proceeding through
      the entire palindromic insert.

PMID- 1388312
TI  - Dissociation of cortisol and adrenal androgen secretion in poorly controlled
      insulin-dependent diabetes mellitus.
AB  - In acute illness, cortisol secretion increases whereas that of the adrenal
      androgens, dehydroepiandrosterone and dehydroepiandrosterone sulfate declines.
      The present study examined if a similar dissociation of cortisol and adrenal
      androgen secretion occurs in poorly controlled diabetes mellitus. Serum
      concentrations of cortisol, dehydroepiandrosterone and dehydroepiandrosterone
      sulfate obtained at 08.00 were compared in 13 post-pubertal diabetics (mean age
      18.0 years) in good control (HbA1C less than 8.0%) and 10 post-pubertal diabetics
      (mean age 17.0 years) in poor control (HbA1C greater than 10.0%). Those in poor
      control had significantly higher serum cortisol (597 +/- 94 nmol/l vs 479 +/-
      208, p less than 0.05), lower dehydroepiandrosterone (13.1 +/- 5.5 nmol/l vs 25.3
      +/- 16.9, p less than 0.025) and lower dehydroepiandrosterone sulfate (4.5 +/-
      2.4 mumol/l vs 7.0 +/- 3.7, p less than 0.025). The ratios of
      dehydroepiandrosterone and dehydroepiandrosterone sulfate to cortisol were also
      significantly lower in those with poor control. It is concluded that poor control
      of insulin-dependent diabetes mellitus results in a dissociation of cortisol and
      adrenal androgen secretion.

PMID- 1388313
TI  - The pituitary-gonadal axis in women with benign or malignant ovarian tumors.
AB  - The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      human chorionic gonadotropin (hCG), estradiol, progesterone, androstenedione,
      testosterone (total and free) and dehydroepiandrosterone sulphate (DHEAS) were
      investigated prior to surgery in 24 postmenopausal women with benign and 28
      postmenopausal women with malignant epithelial ovarian tumors. The serum
      concentrations of hormones were compared with those of 28 healthy,
      postmenopausal, age-matched controls. Significantly lower serum FSH levels were
      demonstrated in women with malignant tumors. No significant differences were
      found between the groups regarding the serum LH levels. The hCG levels were low
      in all groups. Regarding progesterone and estradiol levels, low postmenopausal
      steroid levels were found in all groups examined and no significant differences
      were demonstrated within the groups. No significant correlations between the
      levels of estradiol and FSH or progesterone and LH were demonstrated. To exclude
      a central depression of gonadotropin release mediated by the dopaminergic system
      we examined the thyroid stimulating hormone (TSH) and prolactin. No differences
      were found between the groups regarding TSH and prolactin levels. A possible
      relationship between other hormones/factors produced by the tumor and exerting a
      negative feedback, either centrally or directly, on the gonadotropin release
      remains to be investigated. A change in biological activity in the gonadotropins
      might explain the present findings.

PMID- 1388314
TI  - Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses
      to angiotensin II in pregnant conscious goats.
AB  - This study was designed to examine the actions of ANP in acute, ANGII-mediated
      hypertension during pregnancy. Effects on blood pressure, blood volume, and renal
      Na and K excretion were evaluated in conscious goats (n = 6). ANP (2 micrograms
      min-1), ANGII (0.5 microgram min-1), or ANGII+ANP (doses the same as for each
      peptide alone) was infused intravenously for 60 min. The pressor response to
      ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not
      in diastolic pressure. ANP decreased pressure by 5-10 mmHg both in pregnancy and
      in non-pregnancy. When ANGII+ANP was infused, blood pressure initially rose as
      with ANGII but then declined. ANP suppressed only the elevated systolic pressure.
      Plasma protein concentration and haematocrit was reduced by ANGII but increased
      by ANP alone or together with ANGII, thereby implying fluid shift into the
      vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na
      excretion to 1500 mumol min-1 in non-pregnancy, but only to half of that in
      pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced
      natriuresis to near 3000 mumol min-1 in both non-pregnant and pregnant goats. In
      summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in
      pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in
      non-pregnant goats. This implies that with the present combination ANP and ANGII
      caused a near maximal natriuretic response that was not modified by the systemic
      cardiovascular changes occurring in pregnant goats.

PMID- 1388315
TI  - Effects of cyclopiazonic acid, an inhibitor of the Ca++ ATPase of sarcoplasmic
      reticulum, on Ca++ transport, contraction and relaxation in cardiac muscle.
AB  - Cyclopiazonic acid is a potent inhibitor of cardiac sarcoplasmic reticulum Ca++
      ATPase. It scarely affects inotropism but significantly impairs lusitropism
      suggesting a greater role for cardiac sarcoplasmic reticulum in the control of
      cardiac relaxation than in the control of cardiac contraction.

PMID- 1388316
TI  - Evidence for the existence of endothelial factors regulating contractility in rat
      heart.

PMID- 1388317
TI  - Characterization of a muscle membrane ATPase glycoprotein.

PMID- 1388318
TI  - Suppression of the Arthus reaction by Y-24180, a potent and specific antagonist
      of platelet-activating factor.
AB  - A novel and potent antagonist of platelet-activating factor (PAF), Y-24180 (4-(2
      chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H- thieno[3,2
      f][1,2,4]triazolo[4,3-a][1,4] diazepine) was investigated for the effects on the
      skin reactions induced by chemical mediators and the Arthus reactions. In the rat
      dorsal skin, Y-24180 (0.1-10 mg/kg, p.o.) inhibited increase in vascular
      permeability by the intradermal PAF injection in a dose dependent manner and the
      inhibitory activity was 60 times more potent than that of WEB 2086. While even at
      doses as large as 10 mg/kg, p.o., it had no effect on vascular permeability in
      the rat skin induced by histamine, serotonin, bradykinin and leukotriene D4. On a
      reversed passive Arthus reaction in rat dorsal skin, Y-24180 (0.1-1 mg/kg, p.o.)
      markedly inhibited vascular permeability in a dose dependent manner and the
      inhibitory activity was 15 times more potent than that of WEB 2086. Y-24180 also
      inhibited the Arthus dermal reaction in rabbits (0.03-0.3 mg/kg, p.o.) and guinea
      pigs (0.1-1 mg/kg, p.o.). In addition, Y-24180 (0.1-10 mg/kg, p.o.) significantly
      reduced the exudate volume and the number of infiltrated inflammatory cells in
      the reversed passive Arthus pleural reaction in rats. Furthermore, in rat passive
      Arthus pancreatitis, Y-24180 (0.3-10 mg/kg, p.o.) significantly inhibited the dye
      extravasation from the pancreas. These results provide strong evidence that
      endogenous PAF plays an important role as a mediator in the type III allergic
      inflammation.

PMID- 1388320
TI  - In vitro effects of Etodolac and acetylsalicylic acid on human chondrocyte
      metabolism.
AB  - The effects of two nonsteroidal anti-inflammatory drugs (NSAIDs), Etodolac (ETO)
      and acetylsalicylic acid (ASA), used at pharmacological concentrations, were
      tested on several metabolic parameters of human chondrocytes cultivated in three
      dimensional culture. The results indicated that proteoglycan synthesis was
      significantly decreased by ASA treatment, whereas Etodolac did not affect this
      parameter. Neither ASA nor Etodolac modified type-II collagen production. Both
      NSAIDs were potent inhibitors of PGE2 production, but Etodolac was more efficient
      at equimolar concentrations. In contrast, collagenolytic activity was unaffected
      by Etodolac.

PMID- 1388321
TI  - [Laparoscopic pelvic lymphadenectomy in patients with localized prostate cancer].
AB  - Laparoscopic pelvic lymphadenectomy is a newly developed technique of lymph node
      dissection in patients with malignancy of the pelvic organs. Three patients with
      localized prostatic cancer underwent laparoscopic pelvic lymphadenectomy. The
      patients were 77 years old with stage C disease, 73 with stage B1, and 65 with
      stage A2. Five to ten lymph nodes were removed from each patient after
      laparoscopic procedures lasting 220 to 270 minutes. There were no complications
      during the procedures and their convalescence was uneventful. All lymph nodes
      were negative by pathological examination and a radical retropubic prostatectomy
      was done 2 weeks after the lymphadenectomy in two patients. The other patient was
      treated with external radiotherapy and bilateral orchiectomy. Patients with stage
      C cancer, a high serum level of prostate specific antigen or a high grade tumor
      are the best candidates for this less invasive staging procedure. The
      disadvantage of this procedure is long operation time and complications due to
      CO2 pneumoperitoneum.

PMID- 1388319
TI  - Dimaprit--induced neurotoxicity.
AB  - The neurotoxicity of the histamine H2 agonist dimaprit was characterized.
      Dimaprit (100 micrograms administered into the lateral cerebral ventricle)
      induced a large area of brain necrosis 1-3 days later which was uniformly lethal.
      Lower doses caused dose - related effects on survival, gross brain pathology and
      body weight. Experiments with other H2 agonists and H2 antagonists, together with
      studies by others demonstrating a similar toxicity of the congener homodimaprit
      suggest that the neurotoxicity of dimaprit is independent of brain H2 receptors.
      Although dimaprit is a useful tool for the characterization of H2 receptor
      responses, the present results show that this agent must be used with caution, if
      at all, in classifying brain H2-receptor mediated events.

PMID- 1388322
TI  - Atrial natriuretic peptide in severe heart failure: response to controlled
      changes in atrial pressures during intravenous nitroglycerin therapy.
AB  - Atrial natriuretic peptide (ANP) levels were measured in 17 patients with severe
      congestive heart failure (New York Heart Association functional class IV), and
      the response of the peptide was studied during changes in cardiac filling
      pressures induced by a 24-hour infusion of nitroglycerin. In the control state
      plasma ANP levels (687 +/- 551 pg/ml) were 10-fold normal. During the
      administration of nitroglycerin, natriuretic peptide levels decreased (p less
      than 0.005) with changes matching very closely the decreases in pulmonary
      arterial wedge and right atrial pressures, a 1% mean decrease in the peptide
      level for every 1.5 to 2% mean change in atrial filling pressures. In patients
      with hemodynamic tolerance to constant-dose nitroglycerin infusion, the resulting
      increase in atrial pressures was accompanied by an appropriate secondary increase
      in the plasma ANP level. During the 24-hour study period there was a direct
      linear relationship between both wedge (r = 0.93, p = 0.007) and right atrial (r
      = 0.93, p = 0.008) pressures and the plasma ANP level, with a zero-pressure ANP
      intercept near normal (69 pg/ml for wedge, 174 pg/ml for right atrial pressure).
      The findings were no different in a subgroup of five patients receiving
      simultaneous treatment with captopril, except that plasma renin activity was
      higher and the aldosterone level lower than in the control group by a factor of
      approximately 2.5. The close relationship and tracking of atrial pressure and
      natriuretic peptide curves suggested that the sensitivity of the atrial stretch
      response to changes in atrial filling pressures was maintained in severe
      congestive heart failure.

PMID- 1388323
TI  - Cardiomegaly on chest x-ray: prognostic implications from a ten-year cohort study
      of elderly subjects: a report from the Bronx Longitudinal Aging Study.
AB  - This report is from a 10-year cohort study of community-dwelling elderly men and
      women. Mean age at the time of entry into the study was 79 years. Annual chest x
      ray studies were performed, and data are presented regarding prevalence,
      incidence, and prognosis of cardiomegaly. Cardiomegaly was defined as a
      transverse diameter of the cardiac silhouette greater than or equal to 50% of the
      transverse diameter of the chest (increased cardiothoracic ratio). At the time of
      entry into the study 110 subjects (23%) had cardiomegaly. After 10 years, 51% of
      the subjects with cardiomegaly at baseline died compared with 33% of the subjects
      without cardiomegaly (mortality rate = 9.1 vs 4.8/100 person-years respectively;
      p = 0.014). Cardiovascular disease incidence was also higher for those with
      preexisting cardiomegaly at baseline (rate 9.1 vs 6.1/100 person-years; p =
      0.0001). According to the Cox proportional hazards regression analysis, age,
      cardiomegaly, diabetes, and prior evidence of myocardial infarction were
      independent predictors for death in this cohort. Similarly, the best predictive
      variables for cardiovascular disease were age, diabetes, prior evidence of
      myocardial infarction, and cigarette smoking. Of the 359 subjects without
      cardiomegaly at baseline, 108 (30%) showed evidence of new cardiomegaly, and
      their risk of cardiovascular disease was 1.8 times that of subjects whose test
      results were negative for cardiomegaly throughout the study (p = 0.003). Thus
      cardiomegaly, as defined by an increased cardiothoracic ratio on x-ray films,
      irrespective of cause, is associated with a poor prognosis in very elderly men
      and women.

PMID- 1388324
TI  - Dynamic left ventricular outflow tract obstruction 4 years after aortic valve
      replacement.

PMID- 1388325
TI  - The role of gender in echocardiographically determined left ventricular mass in
      equally trained populations of runners.

PMID- 1388326
TI  - Measurement of volumetric coronary blood flow with a Doppler catheter: validation
      in an animal model.
AB  - Although Doppler catheter recordings are used to determine coronary flow
      velocity, their accuracy in the estimation of volumetric blood flow has not been
      validated. To address this issue, Doppler-derived coronary flow was measured in a
      canine model and compared with that obtained by means of an electromagnetic
      flowmeter. A carotid artery-to-circumflex coronary artery shunt was created in
      six dogs with tubing that incorporated an inline electromagnetic flow device. The
      circumflex artery was occlusively cannulated by means of a rigid metal stent of
      known internal diameter, which was placed 2 cm into the vessel, and flow was
      measured in the stent region by means of a 3F Doppler catheter. Analysis of
      Doppler shift signals was performed by means of a zero-crossing detector (ZCD)
      and an off-line fast-Fourier transformation (FFT) system. Flow derived from peak
      FFT velocities corresponded closely to electromagnetic flow (slope 1.09, r =
      0.93), whereas mean FFT and ZCD velocities underestimated electromagnetic flow
      (with slopes of 0.47 and 0.46, respectively) despite a close correlation (r =
      0.92, 0.94). Thus FFT analysis of the Doppler signal with determination of peak
      velocity gives the most accurate representation of flow, whereas measurements
      based on ZCD mean velocities may significantly underestimate coronary flow.

PMID- 1388327
TI  - Effect of gallopamil on electrophysiologic abnormalities and ventricular
      arrhythmias associated with left ventricular hypertrophy in the feline heart.
AB  - Left ventricular hypertrophy increases vulnerability to ventricular fibrillation.
      To determine whether calcium channel blockade protects against ventricular
      arrhythmia in left ventricular hypertrophy, we studied the effects of gallopamil,
      a potent and specific calcium channel antagonist, in 37 cats undergoing aortic
      banding (group 1, n = 28) or a sham procedure (group 2, n = 9). Each cat
      underwent serial echocardiography and was studied after the development of left
      ventricular hypertrophy, defined as an increase of at least 30% in left
      ventricular posterior wall thickness. After baseline electrophysiologic testing,
      animals received gallopamil (70 micrograms/kg loading dose followed by 2.5
      micrograms/kg/min infusion) (n = 19) or a control infusion of saline solution (n
      = 18), and testing was repeated. There was no significant difference between
      groups 1 and 2 in baseline excitability thresholds intraventricular conduction
      times, ventricular effective refractory periods, or monophasic action potential
      durations. Thresholds for induction of ventricular fibrillation were lower in
      group 1 than in group 2, and only in group 1 was ventricular fibrillation
      inducible during programmed stimulation. This altered vulnerability was
      associated with a significantly greater dispersion of excitability thresholds,
      ventricular effective refractory periods, and monophasic action potential
      durations. Gallopamil did not change baseline measurements except for prolonging
      sinus cycle length and atrioventricular conduction time.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1388328
TI  - Assessment of the efficacy and safety of antiarrhythmic therapy for chronic
      atrial fibrillation: observations on the role of trial design and implications of
      drug-related mortality.
AB  - The findings in clinical trials of antiarrhythmic drug efficacy and safety are
      frequently difficult to compare, since study design often has an important effect
      on trial outcome. To explore this problem further, we compared three designs-
      randomized control, nonrandomized control, and uncontrolled--collectively
      enrolling 2415 patients in 21 trials reporting on the role of quinidine in the
      prevention of chronic atrial fibrillation. The proportion of patients remaining
      in sinus rhythm at 3, 6, and 12 months after cardioversion was calculated by
      means of Kaplan-Meier techniques, and the data were pooled for each trial design.
      For the randomized control trials the difference in the absolute percentage of
      patients remaining in sinus rhythm in the quinidine and control groups was 24% at
      each of the three follow-up intervals. Contrary to findings in the randomized
      control trials, the magnitude of the treatment benefit in nonrandomized trials
      was smaller and declined markedly over time. The percentage of patients remaining
      in sinus rhythm in the uncontrolled trials was intermediate to the percentages in
      the other two trial designs. When the data from all three trial designs were
      pooled, the crude mortality rate was 2.0% in quinidine-treated patients and 0.6%
      in control patients. Sudden cardiac death or ventricular fibrillation was the
      cause of death in 13 of 19 patients for whom the cause of death was known,
      highlighting the potential risk of quinidine-induced proarrhythmia. Although
      quinidine is effective in maintaining sinus rhythm, estimates of the treatment
      effect vary among trial types.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388329
TI  - Effects of calcitonin gene-related peptide on cardiac contractility, coronary
      hemodynamics and myocardial energetics in idiopathic dilated cardiomyopathy.
AB  - This study was performed to examine the effects of calcitonin gene-related
      peptide on cardiac function and coronary circulation in patients with heart
      failure. Synthetic human calcitonin gene-related peptide was infused in the left
      main coronary artery of 9 patients undergoing cardiac catheterization at
      different doses corresponding to incremental infusion rates of 15, 50, 150 and
      600 pmol.min-1. No hemodynamic change was observed in response to administration
      of the 2 lowest doses. The 2 highest doses induced an increase in cardiac index
      and a decrease in systemic arterial pressure. The infusion of 600 pmol.min-1
      resulted in a decrease of mean systemic arterial pressure (86.8 +/- 6.5 to 71.8
      +/- 4.9 mm Hg; p less than 0.01), and an increase in both cardiac index (2.1 +/-
      0.1 to 3.1 +/- 0.17 liters.min-1.m-2; p less than 0.01) and heart rate (87 +/-
      3.7 to 101 +/- 6.1 beats.min-1; p less than 0.01). These hemodynamic changes were
      associated with a significant increase in plasma norepinephrine and epinephrine
      concentrations. Peak positive first derivative of left ventricular pressure did
      not change at any infusion rate. Left ventricular end-diastolic pressure
      decreased at the 2 highest doses associated with a decrease in plasma atrial
      natriuretic factor concentration (730 +/- 140 to 436 +/- 115 pg.ml-1; p less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388330
TI  - Influence of left ventricular hypertrophy and function on the occurrence of
      ventricular tachycardia in hypertrophic cardiomyopathy.
AB  - Sixty-nine patients with hypertrophic cardiomyopathy were studied by 2
      dimensional and Doppler echocardiography and 72-hour Holter monitoring to examine
      the relation between the degree of left ventricular (LV) hypertrophy and
      dysfunction and the occurrence of ventricular tachycardia (VT). Episodes of
      nonsustained VT were detected in 20 patients (29%). Maximal wall thickness was
      not different between patients with (22 +/- 5 mm) and without (21 +/- 5 mm) VT.
      Total hypertrophy score, calculated as the sum of 10 segmental wall thicknesses,
      was also similar in both groups (157 +/- 22 and 153 +/- 32 mm, respectively; p =
      not significant). Furthermore, no significant differences were found between the
      2 groups in LV end-diastolic dimension (41 +/- 7 vs 40 +/- 6 mm), fractional
      shortening (33 +/- 7 vs 34 +/- 10%) and left atrial size (40 +/- 10 vs 41 +/- 11
      mm). An LV outflow tract gradient was detected in 25% of patients with and 35%
      without VT (p = not significant). One or more Doppler indexes of diastolic
      function were abnormal in 70% of patients, but no difference in any of these
      indexes was found between those with and without VT. In summary, the occurrence
      of VT in hypertrophic cardiomyopathy is not related to the degree of LV
      hypertrophy, outflow tract gradient or dysfunction. This finding suggests a
      dissociation between the arrhythmogenic substrate and echocardiographic features
      of the disease.

PMID- 1388331
TI  - Stability of ondansetron hydrochloride in portable infusion-pump reservoirs.
AB  - The stability of ondansetron hydrochloride 0.24 and 2 mg/mL when delivered by
      portable infusion pump at near-body temperature over various time periods was
      investigated. Nine 100-mL drug reservoirs were prepared, three containing
      ondansetron hydrochloride 2 mg/mL and six containing ondansetron hydrochloride
      diluted with 0.9% sodium chloride injection to 0.24 mg/mL. Three of the
      reservoirs containing the diluted solution were refrigerated for up to 30 days at
      3 degrees C before being attached to portable infusion pumps and pumped over 24
      hours at 30 degrees C. The remaining six reservoirs were attached to pumps
      immediately after being filled, and the solutions were delivered for up to 24
      hours (the diluted solution; three reservoirs) or up to seven days (the
      concentrated solution; three reservoirs) at 30 degrees C. Samples were taken
      initially and periodically and analyzed by high-performance liquid chromatography
      and with a pH meter. Both the diluted and the concentrated solutions of
      ondansetron hydrochloride retained at least 95% of the initial drug concentration
      under all the conditions studied. There was no appreciable change in pH.
      Ondansetron hydrochloride 0.24 mg/mL was stable when stored for up to 30 days at
      3 degrees C and infused over 24 hours at 30 degrees C. Ondansetron hydrochloride
      2 mg/mL was stable when infused for up to one week at 30 degrees C.

PMID- 1388332
TI  - Ureter injury during laparoscopy-assisted vaginal hysterectomy with the
      endoscopic linear stapler.
AB  - Ureter injury is more common with abdominal hysterectomy than vaginal
      hysterectomy. Complications during laparoscopy-assisted vaginal hysterectomy
      cases have not been thoroughly studied. Two cases are presented that highlight
      urologic misadventures, specifically, ureteral injury, with the endoscopic linear
      stapler during laparoscopy-assisted vaginal hysterectomy.

PMID- 1388333
TI  - Four ovarian cancers diagnosed during laparoscopic management of 1011 women with
      adnexal masses.
AB  - OBJECTIVES: This study was conducted to assess the value of laparoscopic
      management of adnexal masses. Two concerns we wish to address are the failure to
      diagnose early ovarian cancer at laparoscopy and worsening the prognosis of stage
      I cancer by spilling fluid during surgery. STUDY DESIGN: The setting is a
      predominantly referral-based, private subspecialty practice. All operations were
      preformed in the outpatient surgical suite of a large suburban hospital. After
      extensive patient screenings, which included history and physical examination,
      preoperative serum CA 125 levels (since 1988), and pelvic ultrasonography, 1209
      adnexal masses were managed laparoscopically. RESULTS: Of 1011 patients with
      surgical management, ovarian cancer was discovered intraoperatively in four.
      CONCLUSIONS: Our findings indicate that with consistent use of frozen sections of
      all cyst walls and suspicious tissue, laparoscopic management did not alter the
      prognosis. Neither CA 125 level, pelvic ultrasonography, nor peritoneal cytologic
      testing had sufficient diagnostic specificity to predict malignancy. Experienced
      surgeons using intraoperative histologic sampling may safely evaluate adnexal
      mass laparoscopically.

PMID- 1388334
TI  - Melancholic/endogenous depression and response to somatic treatment and placebo.
AB  - OBJECTIVE: The authors' goals were to examine the effects of somatic treatment
      and placebo in patients with and without endogenous/melancholic depression.
      METHOD: Before entry into one of four trials of antidepressant drugs versus
      placebo, 231 patients were assessed as to whether they met Research Diagnostic
      Criteria for definite endogenous depression and/or DSM-III criteria for major
      depressive episode with melancholia. These patients were prospectively assessed
      for subsequent response to antidepressant treatment or placebo. Previous studies
      of the effect of endogenous/melancholic depression on treatment response were
      also reviewed. RESULTS: Of the 76 patients with DSM-III melancholia given active
      medication, 41 (54%) had a complete or partial response, but only 10 (23%) of the
      44 patients with melancholia given placebo had a complete or partial response. Of
      the 76 depressed patients without melancholia given active medication, 46 (61%)
      had a complete or partial response, and 15 (43%) of the 35 depressed patients
      without melancholia given placebo had a complete or partial response. Moderately
      depressed patients with DSM-III melancholia had a significantly better response
      to active medication than did severely depressed patients with melancholia and
      showed the greatest difference between response to active medication and response
      to placebo. The results of the review of previous studies of the effect of
      endogenous/melancholic depression on treatment response were mixed. CONCLUSIONS:
      Depressed patients with melancholia were not particularly different from
      depressed patients without melancholia in their responses to antidepressant
      medication but did differ from patients without melancholia in their responses to
      active medication versus placebo, particularly if their depression was moderate
      and not severe. This suggests that patients with DSM-III melancholia may be
      unresponsive to nonsomatic treatments.

PMID- 1388335
TI  - Acute exacerbation of body dysmorphic disorder during tryptophan depletion.

PMID- 1388336
TI  - Vomiting after alfentanil anesthesia: effect of dosing method.
AB  - This double-blind study correlated the association of nausea and vomiting after
      alfentanil with its method of administration (bolus dose vs continuous infusion).
      Of 40 women undergoing lower abdominal gynecologic or laparoscopic surgery, 20
      received an intravenous alfentanil (30 micrograms/kg) bolus dose for induction of
      anesthesia, with subsequent bolus doses of 10 micrograms/kg every 10 min, and 20
      received the same induction dose delivered over 1 min, followed by an intravenous
      infusion at 1.0 micrograms.kg-1.min-1. The infusion group experienced more
      frequent nausea and vomiting than the bolus dose group (50% vs 30%, respectively;
      P = 0.0001). Laparoscopic surgery affected the incidence of nausea and vomiting
      independently of the method of alfentanil administration (75% for laparoscopic vs
      17% for incisional procedures; P = 0.0001). Laparoscopy and alfentanil infusion
      combined synergistically to worsen the incidence of nausea and vomiting. We
      conclude that alfentanil infusion for laparoscopic surgery entails a high risk
      for nausea and vomiting.

PMID- 1388337
TI  - Ondansetron in the treatment of postoperative vomiting: a randomized, double
      blind comparison with droperidol and metoclopramide.
AB  - The prophylactic antiemetic efficacy of ondansetron was evaluated in a
      randomized, double-blind comparison with droperidol and metoclopramide in 66
      patients undergoing general anesthesia for dilatation and curettage. Ten minutes
      before induction of anesthesia, 22 patients received a single intravenous dose of
      8 mg of ondansetron, 22 others received 1.25 mg of droperidol, and the remaining
      22 received 10 mg of metoclopramide. Anesthesia was induced with 3.3-5 mg/kg of
      intravenous thiopental and maintained with 65% nitrous oxide in oxygen and 2%-3%
      enflurane. Postoperatively, the incidence of vomiting was 13% with ondansetron,
      45% with droperidol, and 54% with metoclopramide (P less than 0.05; overall chi 2
      test). There was no statistically significant difference in the incidence of
      nausea among the groups. Postoperative sedation and well-being scores were not
      significantly different among the groups. We conclude that preoperative
      prophylactic administration of ondansetron is superior to droperidol or
      metoclopramide in the prevention of emetic sequelae after general anesthesia for
      dilatation and curettage.

PMID- 1388338
TI  - Comparative effects of ketorolac, dezocine, and fentanyl as adjuvants during
      outpatient anesthesia.
AB  - The comparative effects of ketorolac, dezocine, and fentanyl were evaluated in
      136 healthy female patients undergoing outpatient laparoscopic procedures
      according to a randomized, double-blind protocol. Patients received ketorolac (60
      mg) or dezocine (6 mg) or fentanyl (100 micrograms, control group) before the
      start of the operation. A standardized general anesthetic technique consisting of
      midazolam (2 mg), fentanyl (50 micrograms), and propofol (2 mg/kg) for induction
      of anesthesia followed by propofol (120 micrograms.kg-1.min-1), vecuronium (1-2
      mg), and 67% nitrous oxide in oxygen for maintenance of anesthesia, was used. In
      the postanesthesia care unit, 61% of patients in the fentanyl group received
      analgesic drugs for persistent pain, compared with 34% and 25% in the ketorolac
      and dezocine groups, respectively. Similarly, less postoperative fentanyl (mean
      +/- SD) was required in the ketorolac (22 +/- 33 micrograms) and dezocine (18 +/-
      35 micrograms) groups, compared with the fentanyl (58 +/- 71 micrograms) group.
      However, 52% of the patients receiving dezocine required antinausea therapy in
      the postanesthesia care unit, compared with 20% and 18% in the fentanyl and
      ketorolac groups, respectively. Finally, recovery times were significantly
      shorter in the ketorolac (vs dezocine) group. Although both ketorolac and
      dezocine were effective alternatives to fentanyl when administered during
      outpatient laparoscopy, dezocine was associated with an increased incidence of
      postoperative nausea and a delayed discharge time compared with ketorolac.

PMID- 1388339
TI  - [Acrosyndrome disclosing protein S deficiency in human immunodeficiency virus
      infection].

PMID- 1388340
TI  - [Generalized exanthematous pustulosis caused by buphenine: report of a case].

PMID- 1388341
TI  - [A case for diagnosis: palmar erythema caused by salbutamol].

PMID- 1388342
TI  - [Diagnosis of maculopapular rash].

PMID- 1388343
TI  - Zones of the lower transverse rectus abdominis musculocutaneous flap based on
      laser Doppler flowmetry.
AB  - Improvement in the reliability of the lower transverse rectus abdominis
      musculocutaneous flap for breast reconstruction using autogenous tissues has been
      predicated on a thorough analysis of the vascularization of this flap and methods
      for its preservation. The arbitrary division of the skin paddle into zones based
      on relative perfusion has simplified an appreciation of the underlying vascular
      anatomy. Laser Doppler flowmetry has been used to confirm these anatomical
      findings and establish a single system based on descending values of observed
      blood flow. Zone I has been assigned to that region overlying the ipsilateral and
      zone III the contralateral rectus sheath, whereas zone II corresponds to the
      ipsilateral and zone IV the contralateral superficial inferior epigastric
      territory.

PMID- 1388344
TI  - Assessment of TRAM flap perfusion using laser Doppler flowmetry: an adjunct to
      microvascular augmentation.
AB  - Any necrosis after reconstruction of the modified radical mastectomy defect using
      a superior epigastric based unipedicled lower transverse rectus abdominis
      myocutaneous flap should be unusual. Identification of the marginal flap at risk
      for this complication is important as this would permit immediate microvascular
      augmentation to enhance total survival. The dilemma, then, is how to define which
      flaps would benefit. We believe this is possible using laser Doppler flowmetry as
      a continuous, noninvasive, objective monitor of flap perfusion. Flow
      characteristics have been obtained in 16 consecutive transverse rectus abdominis
      myocutaneous flaps using the laser Doppler, where 2 were shown to have been in
      jeopardy for major flap loss. After appropriate microanastomoses as indicated,
      all flaps totally survived as predicted.

PMID- 1388345
TI  - [Prevention of liver metastasis by intrasplenic injection of OK-432].
AB  - The effects of OK-432 on artificial liver metastasis of tumor-bearing mice were
      assessed using murine colon adenocarcinoma MCA-38 in C57 BL/6 mice. OK-432
      injection into the spleen reduced the liver metastases. In gastro-intestinal
      cancer patients, the effects of OK-432 injection into the spleen were assessed
      with functional T cell subsets. The treatment resulted in an increase in the
      number of cytotoxic T cells, but a decrease in the suppressor T cells. The facts
      suggested that OK-432 injection into the spleen had an ability to prevent liver
      metastases.

PMID- 1388346
TI  - [Calcium transport in cells of Streptomyces chrysomallus var. macrotetrolidi-- a
      producer of macrotetrolide antibiotics].
AB  - The dynamics of calcium accumulation by cells in batch cultures and by washed
      cells was defined with a radiotracer procedure for Streptomyces chrysomallus var.
      macrotetrolidi producing ionophore macrotetrolide antibiotics. It was shown that
      macrotetrolides added to the cultivation medium could regulate intracellular
      contents of calcium by participating in cation transport. Moreover, possible
      functioning of a Ca-ATPase system for the calcium active transport in the
      streptomycete cells was demonstrated.

PMID- 1388347
TI  - [Outcome of patients with Eisenmenger syndrome. Apropos of 62 cases followed-up
      for an average of 16 years].
AB  - In an era when heart-lung transplantation offers a therapeutic option for
      patients with Eisenmenger's syndrome, it is important to assess the natural
      history of this condition. With this objective the authors studied 62 patients
      followed-up by the same cardiologist. The average follow-up period was 16 years,
      but 22 patients were followed up for over 20 years. The average age at death was
      29 years. It differed significantly for genetically normal patients (31 years for
      21 fatalities) compared with a population of trisomics (21 years for 6
      fatalities). Half the patient population lived for over 30 years. Fourteen of the
      27 deaths occurred during the third decade and only 4 before the age of 20. The
      probability of surviving 10 more years for a 20 years old genetically normal
      patient was 56%. The causes of death in the 19 cases in which it could be
      established were: 5 sudden deaths, 4 right heart failures, 3 massive haemoptyses,
      3 pulmonary emboli, 2 pneumonias and 2 peroperative deaths. The functional
      disability was nearly always minimal or mild, enabling the patient to work: 24 of
      the 45 non-trisomic patients had full-time jobs. Pregnancy was a poor prognosis
      factor and could be lethal (2 deaths due to pulmonary embolism in the post-partum
      period). A heart-lung transplantation would only seem to be justified in patients
      with severe symptoms, polycythaemia, irreversible right heart failure and/or
      haemoptysis.

PMID- 1388348
TI  - [Percutaneous angioplasty of branch pulmonary artery stenosis. A cooperative
      study].
AB  - Fifty balloon angioplasties of branch pulmonary artery stenosis in 34 patients
      aged 4 months to 20 years, performed in 7 French Centres, were included in this
      study: they were performed from 1984 to 1991 and concerned severe stenoses which
      were congenital in 36 cases and secondary to surgery in 14 cases. The criteria of
      inclusion were: diameter of stenosis less than or equal to 8 mm, right
      ventricular systolic pressure (RVP) greater than or equal to 50 mmHg, RVP/aortic
      pressure ratio (RVP/AO) greater than or equal to 50%, and a significant perfusion
      defect on radionuclide angioscintigraphy. There were no operative complications.
      The diameter of the stenosis increased by greater than 40% in 23 cases (46%); in
      only 7 of these cases (14%) did the RVP and RVP/AO ratio decrease by more than
      20%, the RVP being less than 50 mmHg, or did the perfusion scintigraphy improve.
      No cases of restenosis were observed. The reasons for failure are discussed
      together with the limitations of this study. The respective indications of
      surgery and angioplasty are not easy to determine for these complicated lesions.
      New techniques such as the use of stents should improve results.

PMID- 1388349
TI  - [Isolated hemangioma of the left ventricle. Value of coronaroangiography for the
      etiological diagnosis].
AB  - A four year old child was admitted for investigation of a cardiac murmur and
      cardiomegaly. Echocardiography showed a large left ventricular tumour, the
      extension of which was accurately defined by nuclear magnetic resonance imaging
      and the etiology confirmed by coronary angiography. Holter recordings showed
      salvoes of ventricular tachycardia. This is an interesting case because, despite
      echocardiography and nuclear magnetic resonance imaging, the precise nature of
      the tumour was revealed only by coronary angiography. This investigation also
      showed a significant decrease of the left ventricular ejection fraction. It is
      the only described haemangioma complicated by this type of ventricular
      hyperexcitability. Therefore, coronary angiography would seem to be necessary in
      the investigation of isolated myocardial masses which remain unidentified by non
      invasive methods.

PMID- 1388350
TI  - Baby v mother.
AB  - The right of a child born disabled as a result of a negligent act committed by
      another whilst the child was in utero is a recognized principle of law in the
      major common law countries. It is also recognized that a child who suffers
      injuries caused to it due to a negligent act committed prior to conception may
      also have a right to seek compensation. The right to bring such an action is
      contingent upon the child being born alive and being able to prove a causal
      connection between the alleged negligent act and the injuries complained of.
      However, with few exceptions, such legal actions have to date been taken against
      third parties whose negligence allegedly caused the injuries complained of. It
      was only a matter of time before courts would be called upon to consider an
      action taken against the mother of the child for the mother's alleged negligence
      causing harm to the child during pregnancy.

PMID- 1388351
TI  - Late adverse effects of streptokinase.

PMID- 1388352
TI  - Streptokinase morbidity--more common than previously recognised.
AB  - Streptokinase is the thrombolytic agent most commonly used for the treatment of
      acute myocardial infarction. We report eight patients who developed late uncommon
      adverse reactions to streptokinase probably due to immune complex disease. The
      clinical manifestations included vasculitic rashes, abnormal renal and liver
      function tests and a syndrome resembling adult respiratory distress syndrome.
      Major adverse events with streptokinase such as stroke, bleeding and other
      allergic reactions, have been previously documented but the morbidity related to
      delayed reactions has not been widely recognised. These reactions produced
      significant morbidity resulting in prolonged hospital stay and may need to be
      considered in the decision to use streptokinase.

PMID- 1388353
TI  - Cardiovascular disease in patients with end-stage renal failure.

PMID- 1388356
TI  - Nuclear internalisation and DNA binding activities of interleukin-1, interleukin
      1 receptor and interleukin-1/receptor complexes.
AB  - This paper presents evidence to suggest that interleukin-1 alpha as a complex
      with its receptor is able to express DNA binding activity. Both the interleukin
      1/receptor complex and the interleukin-1 receptor appear to be able to bind to
      DNA, however interleukin-1 on its own showed no binding activity. Interleukin-1
      was found to be internalised into the nuclei of all cells examined (EL4, MEL, HL
      60, K562, THP-1 and Jurkat cells). The data suggest the possible modulation of
      genes by interaction of interleukin-1/receptor complexes with DNA structures.

PMID- 1388355
TI  - Changes in the adenine nucleotide and inorganic phosphate content of Escherichia
      coli F1-ATPase during ATP synthesis in dimethyl sulphoxide.
AB  - Escherichia coli F1-ATPase contained 2.9 +/- 0.1 mol of adenine nucleotide and
      3.1 +/- 0.3 mol of Pi/mol of enzyme. After preincubation with ATP, the nucleotide
      and phosphate contents were 5.6 and 6.0 +/- 0.5 mol/mol of enzyme respectively.
      The F1-ATPase was induced to synthesize ATP in the presence of 30% (v/v) dimethyl
      sulphoxide (Me2SO). The ATP originated from endogenous bound ADP. The bound
      adenine nucleotide and Pi contents of the enzyme during the time course of ATP
      synthesis were investigated by using F1-ATPase which had been preincubated with
      ATP. We show that the process of ATP synthesis in Me2SO involves (i) an initial
      rapid loss of nucleotide from the enzyme, the process being facilitated by
      exogenous Pi, (ii) a rapid loss of Pi from the enzyme, at least in the absence of
      exogenous Pi, (iii) re-binding of a portion of the lost nucleotide, and (iv)
      synthesis of ATP from bound ADP and exogenous Pi. It is proposed that transfer of
      the F1-ATPase to the Me2SO medium induces a change in the conformation of the
      enzyme to a form favouring ATP synthesis.

PMID- 1388354
TI  - Definition of surface-exposed and trans-membranous regions of the (Ca(2+)-Mg2+)
      ATPase of sarcoplasmic reticulum using anti-peptide antibodies.
AB  - Peptides have been synthesized representing parts of the transduction,
      phosphorylation, nucleotide-binding and hinge domains of the (Ca(2+)-Mg2+)-ATPase
      of skeletal muscle sarcoplasmic reticulum (SR), and corresponding to segments of
      all of the postulated short inter-membranous loops of the (Ca(2+)-Mg2+)-ATPase
      (residues 77-88, 277-287, 780-791, 808-818, 915-924 and 949-958). A number of
      antibodies raised to these peptides have been shown to bind to the ATPase,
      defining surface-exposed regions. Many of these are concentrated in the
      phosphorylation and nucleotide-binding domains, suggesting that these domains
      could be exposed on the top surface of the ATPase. The cytoplasmic location of
      the loop containing residues 808-818 was confirmed by the finding that proteinase
      K treatment of intact SR vesicles enhanced the binding of antibodies against this
      segment. These findings support the 10-alpha-helix model of the ATPase. These
      results also suggest that only inter-membranous loops larger than about 20
      residues are likely to be detected by immunological methods in transmembranous
      proteins. Binding of anti-peptide antibodies to proteolytic fragments of the
      ATPase has been used to define the domain structure of the enzyme. Some of the
      anti-peptide antibodies have been characterized by studying their binding to sets
      of hexameric peptides synthesized on plastic pegs. A wide pattern of responses is
      observed, with a restricted range of epitopes being recognized by each anti
      peptide antibody.

PMID- 1388357
TI  - Inhibition of nerve growth factor-induced B-50/GAP-43 expression by antisense
      oligomers interferes with neurite outgrowth of PC12 cells.
AB  - Substantial evidence has now been gathered for the involvement of B-50/GAP-43 in
      neuronal development and regeneration. The precise role of this protein, however,
      is still debated. In an earlier study, a linear correlation between NGF-induced
      neurite outgrowth and B-50/GAP-43 levels was observed in PC12 cells. To establish
      the involvement of B-50/GAP-43 expression in neurite outgrowth in these cells, we
      interfered with the expression by antisense oligomers and measured the outgrowth.
      In the present study, a B-50/GAP-43 antisense 5'-oligomer interfered both with
      the NGF-induced increase in B-50/GAP-43 and with neurite outgrowth, whereas an
      antisense 3'-oligomer was ineffective. We conclude, that in PC12 cells under
      normal conditions B-50/GAP-43 expression and neurite outgrowth are or become
      coupled upon NGF-induction, in contrast to the situation in PC12 clones with no
      or very low B-50/GAP-43 expression.

PMID- 1388359
TI  - Review articles and publication bias.
AB  - Publication bias occurs if the results from studies which have not been published
      are different from the published ones. From a Bayesian viewpoint, it also
      concerns non-publication of studies with similar results as the published ones
      because the strength of the evidence will be influenced. Publication bias
      complicates the interpretation of reviews and meta-analyses. If favourable
      results are published more often there will be an overestimation of the effects
      of a treatment. There have been several attempts to assess the magnitude of
      publication bias. Unpublished trials could be identified by means of a survey
      among researchers, and the results could subsequently be compared with the
      outcomes of published trials. Also, the results from published trials could be
      compared with trials from a registry. Furthermore, the results from registered
      but unpublished trials could be compared with those of registered and
      subsequently published trials. Studies addressing publication bias have shown
      that it is a serious problem which complicates the interpretation of reviews. In
      assessments of publication bias other factors must be taken into account. These
      include the mode of publication: refereed journals, other journals, books, etc.
      Differences could also be related to the quality of trials. Finally, the source
      of funding may influence both the results and subsequent publication. Publication
      bias can only be avoided by registration of all trials before data collection is
      started; several of such registries have already been installed. Perhaps, if more
      of such registries exist, reviewers could only use registered trials for their
      main conclusions. All other information could then be considered sensitive to
      publication bias.

PMID- 1388358
TI  - The mechanism of inhibition of the actin-activated myosin MgATPase by calponin.
AB  - Calponin inhibits the actin-activated ATPase of smooth muscle myosin and thus has
      been proposed as a thin filament-based regulatory component in smooth muscle. To
      obtain information on the mechanism of inhibition by calponin we have used
      chemical modification of actin and cross-linking of actin and subfragment 1.
      Modification of Lys 61 of actin had no effect on the inhibition by calponin of
      acto-heavy meromyosin ATPase, i.e. different from tropomyosin-troponin. In
      addition, modification of the acidic N-terminal region of actin did not impair
      the ability of calponin to bind to F-actin. Finally, calponin was effective in
      inhibiting ATPase activity of cross-linked acto-subfragment 1. Therefore the
      mechanism of inhibition by calponin is distinct from troponin-tropomyosin and
      caldesmon in that it does not involve either the N-terminal acidic region of
      actin nor the area around Lys 61 and does not fit a simple steric blocking model.

PMID- 1388360
TI  - Replenishment of brain adenosine triphosphate content by morphinan-type N-methyl
      D-asparatate receptor antagonists, dextrorphan and dextromethorphan through the
      activation of adenylate kinase.
AB  - The in vitro effects of four N-methyl-D-aspartate (NMDA) receptor antagonists,
      dextrorphan, (DX, CAS 125-73-5), dextromethorphan, (DM, CAS 125-71-3),
      dizocilpine (CAS 77086-21-6) and (+/-) 2-amino-7-phosphonoheptanoate (AP-7, CAS
      85797-13-3) on rat brain adenylate kinase (AK) have been studied. DM was the most
      active of the four compounds in increasing rat brain AK activity. DX was slightly
      less active than DM, while the most potent NMDA antagonist, dizocilpine was
      somewhat weaker than the above two morphinan analogs (DX and DM). For AP-7, the
      AK activity was unchanged. The results may indicate that a causal relation cannot
      be made between the activation of the AK by these compounds and their ability to
      act as NMDA antagonists. When DX was added, the Km and Vmax values of the enzyme
      for ADP as a substrate decreased and increased, respectively, possibly reflecting
      an affinity change for the enzyme-substrate interaction by DX. The observed
      increase in the AK activity by the morphinan-type NMDA antagonists in vitro might
      result in their preserving effects on cerebral neuron integrity under the
      conditions where cerebral energy metabolism is disturbed. This assumption was at
      least partly confirmed in in vivo tests in which DX, unlike dizocilpine,
      increased ATP content of the brain in mice under the influence of hypoxia exerted
      by i.v. injection of KCN.

PMID- 1388361
TI  - [Should cell proliferation of breast cancer be quantified, and if so, which
      method should be used].

PMID- 1388362
TI  - [Immunohistochemistry of adnexal tumors of the skin].

PMID- 1388363
TI  - [Rhodococcus equi infection causing pulmonary malacoplakia in a patient with
      acquired immune deficiency syndrome].
AB  - Rhodococcus equi is a pathogen for some animal species. It can cause
      opportunistic pulmonary infections in immunocompromised people. The authors
      describe such an infection that causes malacoplakia in a patient with acquired
      immunodeficiency syndrome. The likeness between lesions due to Rhodococcus equi
      and those due to other opportunistic germs as Mycobacterium avium-intracellulare
      is emphasized.

PMID- 1388365
TI  - [Pseudotumor extramedullary hematopoiesis. Report of 3 cases and review of the
      literature].
AB  - We report 3 cases of extramedullary hematopoiesis with a sacrococcygeal, right
      obturatory hole and paravertebral dorso lumbar locations respectively in 30, 34
      and 58 years old patients (two males and woman). A medullary tuberculosis was
      discovered in one case, a beta thalassemia in the second, and the third was
      classified as idiopathic. Radiologic picture often permitted to evoke the
      diagnosis on the aspect of a well limited multilocular tumor especially when
      there is a paravertebral location as in our third patient. Fine needle punction
      cytologic examination can permit the diagnosis and avoid surgery, except if
      complications occur.

PMID- 1388364
TI  - [Malignant dermoid cyst of the ovary with double tumor cell population, revealed
      by an umbilical metastasis].
AB  - The authors report a case of multiple malignancies (squamous cell carcinoma and
      carcinoid) arising in a dermoid cyst of the ovary. The tumor being revealed by an
      umbilical metastasis. They insist on the rarity of this entity and discuss the
      elements of diagnosis and prognosis through a review of literature.

PMID- 1388366
TI  - [A rare case of congenital tumor: choroid plexus papilloma with cartilaginous
      nodules].

PMID- 1388367
TI  - [An unusual lesion of the ureter].

PMID- 1388368
TI  - Hepatitis B vaccine education programs: what really works?
AB  - 1. Health care workers need to know that hepatitis B vaccine provides a safe,
      effective protection for them against a significant occupational hazard. 2.
      Several theoretical models can be used to design hepatitis B education programs,
      including motivational theories, the Health Belief Model, and andragogy. Specific
      recommendations can be made about the plan, format, content, and evaluation of
      adult education programs about hepatitis B. Federal agencies, including the
      Department of Health and Human Services and the Department of Labor, have
      established criteria for hepatitis B education programs.

PMID- 1388369
TI  - AIDS education strategies: evaluating the fear response.
AB  - 1. Despite educational interventions, evidence suggests that negative attitudes
      about AIDS risk persist among clinical hospital staff. In diverse study
      populations, associations have been found between psychosocial phenomena and on
      the job accidents and injuries. 2. This article describes a pilot study to
      explore whether fearful attitudes of clinicians contribute to the adverse
      behaviors of needlestick injuries and mucosal splashes. The authors sought to
      demonstrate whether desensitization therapy would be effective in reducing fear
      response. 3. A serendipitous finding of the study was that organizational and
      interpersonal conflict frequently provoked fear and anxiety responses. There is a
      continued need to examine the domain of AIDS related fears among clinical staff,
      as well as a need to seek a better understanding of this fear as part of the
      tensions of organizational dynamics in hospitals. 4. Occupational health nurses
      working in hospitals are in a unique position to uncover relationships among all
      types of incidents that may indicate fear and anxiety among clinical staff.

PMID- 1388370
TI  - Machine safety: proper safeguarding techniques.
AB  - 1. OSHA mandates certain safeguarding of machinery to prevent accidents and
      protect machine operators. OSHA specifies moving parts that must be guarded and
      sets criteria for the guards. 2. A 1989 OSHA standard for lockout/tagout requires
      locking the energy source during maintenance, periodically inspecting for power
      transmission, and training maintenance workers. 3. In an amputation emergency,
      first aid for cardiopulmonary resuscitation, shock, and bleeding are the first
      considerations. The amputated part should be wrapped in moist gauze, placed in a
      sealed plastic bag, and placed in a container of 50% water and 50% ice for
      transport. 4. The role of the occupational health nurse in machine safety is to
      conduct worksite analyses to identify proper safeguarding and to communicate
      deficiencies to appropriate personnel; to train workers in safe work practices
      and observe compliance in the use of machine guards; to provide care to workers
      injured by machines; and to reinforce safe work practices among machine
      operators.

PMID- 1388371
TI  - Americans with Disabilities Act: meeting the requirements.
AB  - 1. Title I of the Americans With Disabilities Act prohibits workplace
      discrimination on the basis of disability. 2. An employer is required to provide
      reasonable accommodation so that an otherwise qualified employee can do the job.
      3. Physical examinations that seek to determine whether a person has a disability
      are prohibited. 4. The Equal Employment Opportunity Commission will serve as the
      enforcement agency for the employment requirements of the American With
      Disabilities Act.

PMID- 1388372
TI  - Occupational injuries: a study of health care workers at a northwestern health
      science center and teaching hospital.
AB  - 1. This retrospective study examined the magnitude of the problem of work related
      health hazards affecting professional and non-professional employees of a state
      university health science center and hospital. 2. From the 1,513 injury episodes
      that occurred among the 9,668 employees during the 32 month study period, it was
      determined that the highest risk categories for both department and job were
      nursing, housekeeping, food service, and laboratory technicians. 3. Injury rate
      for females (11.2 per 100 person years) was more than twice that of males (5.1).
      Injury rates declined from 11.6 per 100 person years at ages 25 to 39 to 3.8 at
      ages over 60. Puncture wounds (32.7%), mostly by needlesticks, were the most
      frequently reported injury type, followed by strains and sprains (17.2%),
      lacerations (12.5%), and contusions (12.1%).

PMID- 1388373
TI  - Facilitating an effective meeting.

PMID- 1388374
TI  - Analysis of trauma intubations.
AB  - The timing of trauma patient intubation is dependent on clinical presentation and
      clinician judgment. We sought to correlate the timing of intubation with the
      presenting of physiologic parameters and clinical outcome to identify potential
      quality assurance audit filters. Patients (n = 82) were grouped by timing of
      intubation: PREHOSPITAL, paramedic intubation; IMMEDIATE, within 10 minutes of
      arrival; DELAYED, beyond 10 minutes but within 2 hours of arrival; and NONURGENT,
      beyond 2 hours or at the time of surgery. While mean revised trauma scores and
      Glasgow Coma Scale (GCS) scores differed for the groups, the mean length of
      hospital stay and the incidence of aspiration pneumonia were not significantly
      different. In the DELAYED group, 80% of those who developed aspiration pneumonia
      had a GCS < or = 13. Patients in the NONURGENT group were older and commonly
      presented with tachypnea. The survival rate for the NONURGENT group was lower
      than predicted by the TRISS method (P = .004). A GCS < or = 13 and age greater
      than 50 years with presenting respiratory rates of more than 25 breaths/min
      represent potential trauma intubation audit filters.

PMID- 1388375
TI  - Atropine administration in experimental electromechanical dissociation.
AB  - Atropine can have a place during cardiopulmonary resuscitation (CPR) in the
      management of asystole, where parasympathetic influence might be excessive.
      However, the beneficial effects of atropine in electromechanical dissociation
      (EMD) have not been clearly demonstrated. The authors studied the effects of
      atropine in combination with epinephrine on an experimental model of EMD in the
      closed-chested dog. In 15 pentobarbital-anesthetized, mechanically ventilated
      dogs (mean weight 20 kg), EMD was induced by ventricular fibrillation followed by
      an external countershock, and was observed for 2 minutes before CPR was started.
      After 5 minutes of chest compression using a CPR thumper, either atropine 0.5 mg
      or D5W was administered, and the same injection was repeated every 5 minutes
      until recovery. Epinephrine 1 mg was administered in alternans. Each dog was
      submitted to two successive episodes of CPR, using either atropine or D5W, in a
      randomized order. Of a total of 28 CPRs, five were successful with chest
      compression alone. In the treatment groups, 10 of 11 were successful with
      atropine, but only eight of 12 with D5W (P < .01). The duration of CPR was also
      significantly shorter when atropine was used (9 minutes 56 seconds +/- 14 seconds
      versus 12 minutes 08 seconds +/- 43 seconds, P < .001). During the recovery
      period, atropine-treated animals had higher arterial pressure, heart rate,
      cardiac output and stroke volume. On this experimental model, the administration
      of high doses of atropine together with epinephrine enhances the recovery from
      EMD and results in a better cardiac function during recovery.

PMID- 1388376
TI  - Pulse oximetry and peak flow as indicators of wheezing severity in children and
      improvement following bronchodilator treatments.
AB  - This study examined the changes from the initial peak flows and oxygen
      saturations (OSAT) of wheezing children at presentation to the emergency
      department through their treatment in the emergency department. Data was
      collected prospectively on 785 patients 5 to 20 years of age during an 11-month
      period from November 1, 1990, to September 30, 1991. Both the initial OSAT and
      peak flows were correlated with the number of bronchodilator treatments required
      in the emergency department and with the need for hospitalization. Both the
      initial OSAT and the peak flows had a limited ability to predict the need for
      hospitalization. Oxygen saturation appears to be a valid measure of wheezing
      severity and is more easily obtained in children of all ages. Following
      bronchodilator treatment, peak flow results in a larger quantitative improvement
      than OSAT; however, this difference does not appear to have any significant
      advantage. Aerosolized albuterol and subcutaneous epinephrine resulted in a
      similar degree of improvement as measured by peak flow and by oxygen saturation,
      with clinically similar changes in heart rate.

PMID- 1388377
TI  - Improved outcome with early blood administration in a near-fatal model of porcine
      hemorrhagic shock.
AB  - Current recommendations for the preoperative management of hemorrhagic shock
      include the initial infusion of 2 L of isotonic crystalloid regardless of the
      severity of hemorrhage. While this approach may be adequate for patients who
      experience only mild to moderate hemorrhagic insults, it has never been tested in
      a clinically relevant model of severe life-threatening hemorrhage. The authors
      used a porcine model of rapidly fatal hemorrhage with a reproducible and relevant
      physiologic end-point, the absence of vital signs, to test the hypothesis that
      even brief delays in blood replacement may result in higher mortality rates and
      worsen hemodynamic and metabolic responses to hemorrhage. Twenty-four immature
      swine (11-17 kg) were bled continuously at a decelerating rate until the
      following criteria were met: (1) respiratory arrest, (2) a pulse pressure of 0
      and, (3) a slowing of cardiac electrical activity of 15% or more. Resuscitation
      was begun 1 minute later. The animals were randomly assigned to one of three
      resuscitation regimens. Group A (n = 8) received shed blood at a rate of 3
      mL/kg/min for 10 minutes followed by normal saline (NS) at a rate of 3 mL/kg/min
      for 10 minutes. Group B (n = 8) received NS at a rate of 3 mL/kg/min for 10
      minutes followed by shed blood at a rate of 3 mL/kg/min for 10 minutes. Group C,
      controls, (n = 8) received NS at a rate of 3 mL/kg/min for 20 minutes. Animals
      were observed for 30 minutes after resuscitation or until death. Mortality was
      25%, 37.5%, and 100% for groups A, B, and C, respectively (P < .05 for group C
      versus group A or B).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388378
TI  - Continuous central venous oximetry and shock index in the emergency department:
      use in the evaluation of clinical shock.
AB  - Initial therapy of shock in the emergency department (ED) emphasizes the
      normalization of physiologic variables such as heart rate (HR), mean arterial
      pressure (MAP), and central venous pressure (CVP) rather than restoration of
      adequate tissue oxygenation. After hemodynamic stabilization of MAP, CVP, and HR,
      the authors examined tissue oxygenation as indicated by continuous central venous
      oximetry (SCVO2), lactic acid concentration, and shock index (SI). Sixteen
      consecutive nonrandomized patients presenting to the ED of a large urban hospital
      in shock (MAP < 60 mm Hg, HR > 120 beats/min, and altered sensorium) were
      initially resuscitated with fluid, blood, inotropes, and/or vasoactive drug
      therapy to normalize MAP, CVP, and HR. In addition, SCVO2, arterial lactate
      concentration, and SI were measured after completion of resuscitation in the ED.
      Eight patients (group no. 1) had inadequate tissue oxygenation reflected by low
      SCVO2 (less than 65%). Four patients in group no. 1 had elevated arterial lactic
      acid concentration. All group no. 1 patients had an elevated SI (> 0.7)
      suggesting persistent impairment of left ventricular stroke work. Eight patients
      (group no. 2) had normal or elevated SCVO2 (> 65%). In group no. 2, arterial
      lactic acid concentration was elevated in six and SI in seven patients.
      Normalization of hemodynamic variables does not adequately reflect the optimal
      endpoint of initial therapy in shock in the ED. Most (94%) of these patients
      continue to have significant global ischemia and cardiac dysfunction as indicated
      by reduced SCVO2 and elevated lactic acid concentration and SI. Systemic tissue
      oxygenation should be monitored and optimized in the ED in these critically ill
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388379
TI  - Acute isopropanol ingestion: pharmacokinetic parameters in the infant.
AB  - We describe a case of isopropanol intoxication in a 2-month-old infant. The
      source of isopropanol and both the route and time of ingestion could be clearly
      identified. Serial measurements of isopropanol and acetone provided data for
      calculating their respective elimination half-lives. Isopropanol (half-life = 5.8
      hr) clearance was similar to values reported for adults; acetone (half-life =
      10.8 hr) was eliminated twice as rapidly as in adults.

PMID- 1388380
TI  - Fatal ingestion of boric acid in an adult.
AB  - A 45-year-old white man ingested approximately two cups of boric acid crystals
      dissolved in water in a suicide attempt. Nausea, vomiting, greenish diarrhea, and
      dehydration occurred shortly thereafter. Two days later, he presented to the
      hospital with hypotension, metabolic acidosis, oliguric renal failure, a
      generalized erythematous rash, and several superficial skin abrasions. His
      condition failed to improve despite intravenous fluids and vasopressors. He later
      developed atrial fibrillation with a rapid ventricular response and could not be
      converted to a sinus rhythm. This rhythm deteriorated to electromechanical
      dissociation, and the patient died 17 hours after admission. The urine and whole
      blood boric acid concentrations approximately 52 hours after ingestion were 160
      and 42 mg/dL, respectively. These results are equivalent to urine and blood boron
      concentrations of 28 and 7 mg/dL, respectively. A postmortem urine boron
      concentration was 29.4 mg/dL. The autopsy report listed boron toxicity as the
      cause of death. This is the only adult reported to die from acute boric acid
      ingestion in recent years and may be atypical since the patient was untreated for
      3 days and presented with dehydration and renal function impairment. This case
      suggests that lack of adequate urine flow and dehydration increases the risk of
      boron toxicity.

PMID- 1388381
TI  - Adenosine use in pregnancy: lack of effect on fetal heart rate.
AB  - The treatment for supraventricular tachycardia in pregnancy is somewhat
      controversial. Although a variety of medications have been used to terminate this
      rhythm during pregnancy, all have actual or theoretical drawbacks. Adenosine is a
      relatively new medication with an extremely short half-life and is effective in
      the treatment of supraventricular tachycardia. We report a case in which this
      medication was used successfully during pregnancy. In addition, we found that
      adenosine had no effect on fetal heart rate in this case.

PMID- 1388382
TI  - Angiotensin-converting enzyme inhibitor-induced angioedema: still unrecognized.
AB  - Angiotensin-converting enzyme inhibitors are a widely used antihypertensive
      modality. While they have a favorable side effect profile, there is a .1% to .2%
      incidence of potentially life threatening angioedema. The edema usually presents
      in the head and neck, especially the face, lips, tongue, and glottis. Patients
      may initially be treated with standard anti-allergic therapy; however, the
      situation may dictate a more aggressive therapeutic approach. The authors present
      the case of a patient who presented with angioedema 18 times over a 3-year period
      to qualified emergency physicians before the correct diagnosis of angiotensin
      converting enzyme inhibitor-induced angioedema was made. Despite recent
      literature on the subject, there appears to be a lack of familiarization among
      emergency department physicians regarding this relatively common adverse effect.

PMID- 1388383
TI  - Profound alkalemia during treatment of tricyclic antidepressant overdose: a
      potential hazard of combined hyperventilation and intravenous bicarbonate.
AB  - Two patients with cardiovascular and neurologic toxicity from intentional
      tricyclic antidepressant overdose received bicarbonate infusions in association
      with hyperventilation for alkalinization. Both patients developed profound
      alkalemia. One patient died, and the other patient's alkalemia resolved prior to
      her death. Bicarbonate infusions have become the standard of care for symptomatic
      tricyclic antidepressant toxicity. Severe alkalemia (pH greater than 7.60) in
      other settings has been reported to correlate with higher rates of mortality.
      Careful monitoring of the pH is imperative when bicarbonate therapy is used. It
      is probably prudent to keep the pH level in the range 7.45 to 7.60. Capnography
      may also be useful in monitoring patients during alkalinization.

PMID- 1388384
TI  - Hypoglycemia following albuterol overdose in a child.
AB  - Acute overdose with beta-sympathomimetics results in transient elevation of blood
      glucose levels. Hypoglycemia has previously been reported in newborns of mothers
      following prolonged use of sympathomimetics used as tocolytic therapy. The
      authors report the first case of symptomatic hypoglycemia in a child, occurring
      16 hours after acute albuterol overdose. Hypoglycemia may occur as a complication
      of acute beta-sympathomimetic overdose, probably as a reaction to acute elevation
      of blood sugar and resultant hyperinsulinemia. The authors suggest that in
      children with a large overdose of beta-sympathomimetics, blood glucose levels
      should be monitored for several hours. In those with marked hyperglycemia,
      monitoring should be extended until normalization of blood glucose levels.

PMID- 1388385
TI  - The applications of hyperbaric oxygen therapy in emergency medicine.

PMID- 1388386
TI  - Cases in electrocardiography.

PMID- 1388387
TI  - Emergency physician awareness of the Clinical Laboratory Improvement Amendments
      of 1988.

PMID- 1388388
TI  - Changes in the presentation of intussusception.
AB  - Intussusception is most often diagnosed in well-nourished 7- to 10-month-old
      infants, but may be overlooked in older children. From 1985 to 1991, we treated
      118 boys and 62 girls ranging in age from 2 months to 15 years (average, 22.6
      months). Thirty-seven percent were older than 2 years, significantly more than in
      earlier experience at this institution. Overall, children with intussusception
      had a less than average weight (P < .05). The majority of intussusceptions in all
      age groups were idiopathic. Seventy-three percent of the patients were treated
      successfully by barium enema. The presence of air-fluid levels on the plain
      radiograph decreased the success rate of barium enema reduction from 81% to 49%.
      Barium enema reduction should nevertheless be attempted regardless of the age of
      the patient or the duration of symptoms, and routine surgical exploration is
      never recommended.

PMID- 1388390
TI  - Intranasal midazolam as a sedative for children during laceration repair.
AB  - We performed a retrospective chart review to determine the onset, duration,
      safety, and clinical sedative effects of 0.2 to 0.5 mg/kg intranasal midazolam in
      young children during laceration repair. Of 408 children treated for lacerations
      during an 8-month period, 42 (10%) received intranasal midazolam. Documentation
      was adequate for detailed analysis in 40 cases. Data are reported as mean +/-
      standard deviation and the frequency with 95% confidence limit (CL) estimates.
      The mean age of the study population was 32 +/- 9 months (range 12 months to 6
      years), and the mean body mass was 14.5 +/- 3 kg. Topical or injected local
      anesthesia was used in 37 cases. Overall, 73% (CL 56% to 85%) of the children
      achieved adequate sedation. However, those receiving 0.2 to 0.29 mg/kg had
      adequate sedation in only 27% (CL 6% to 60%) of the cases compared with 80% (CL
      52% to 95%) and 100% (CL 79% to 100%) when 0.3 to 0.39 and 0.4 to 0.5 mg/kg
      respectively were administered. When achieved, sedation occurred within 12 +/- 4
      minutes, recovery occurred at 41 +/- 9 minutes, and discharge occurred at 56 +/-
      11 minutes. No vomiting or clinically significant oxygen desaturation (defined as
      a drop of > 4% or to < 91%) was observed. We conclude that intranasal midazolam
      is a safe and effective sedative for laceration repair under local anesthesia in
      preschool-aged children. We recommend a dose of 0.3 to 0.5 mg/kg, with treatment
      failure less likely after 0.4 to 0.5 mg/kg compared with less than 0.3 mg/kg.

PMID- 1388389
TI  - Whole bowel irrigation in an acute oral lead intoxication.
AB  - An 89-year-old man acutely ingested approximately three ounces of a ceramic glaze
      preparation with a 30% lead oxide content. A blood lead level of 18 micrograms/mL
      was reported from a sample drawn within 1 hour of ingestion and just prior to
      gastric lavage. Following lavage, an abdominal radiograph demonstrated lead
      throughout the small intestine. Whole bowel irrigation was then undertaken and
      subsequent x-rays demonstrated clearing of all lead in the small bowel. At 16 and
      24 hours post-ingestion, blood lead levels rose to 39 micrograms/dL and 42
      micrograms/dL, respectively, and the patient then underwent a 5-day course of
      chelation therapy. This is the first reported case of the use of whole bowel
      irrigation in an acute lead ingestion. The use of decontamination techniques in
      acute lead ingestions is reviewed.

PMID- 1388391
TI  - The limits of health care resources.

PMID- 1388392
TI  - Emergency medical systems in Czechoslovakia.
AB  - The year 1987 witnessed the "velvet revolution" of Vaclav Havel and the beginning
      of democratic reform in Czechoslovakia. As the country struggles to build a
      market-based economy, it maintains a well-developed socialist system of health
      care that is patterned after the former Soviet system and is free to all (Am J
      Emerg Med 1984; 2:455-456). Formal private medical practice does not exist. Non
      emergency care is provided by multispecialty, primary-care oriented clinics
      (polyklinka) where after-hours visits are possible due to the presence of on-call
      physicians. In small towns such an on-call doctor would be a general
      practitioner, but in large cities an internist, pediatrician, and surgeon might
      all be available.

PMID- 1388393
TI  - Trauma: an annotated bibliography of the recent literature.

PMID- 1388394
TI  - Occult cervical spine fractures--a misstated concept.

PMID- 1388396
TI  - Laryngeal edema from celery allergic reaction.

PMID- 1388395
TI  - The unstable occult cervical spine fracture.

PMID- 1388397
TI  - Fictitious hypoxia--a result of misconnection of oxygen tubing to a wall source
      of air.

PMID- 1388399
TI  - A modified method to insert a nasogastric tube without kinking in the nasal
      cavity.

PMID- 1388398
TI  - Avoiding needle-stick injuries in the emergency department.

PMID- 1388400
TI  - Erythromycin-related dystonic reaction.

PMID- 1388401
TI  - Kiss of life mask: evaluation or opinion?

PMID- 1388402
TI  - Increase of heat loss by wearing gloves and boots in wet-suited subjects working
      in cold water.
AB  - The effect of wearing protective gloves and boots on thermal exchanges of wet
      suited subjects in cold water was evaluated. Four male subjects, clad in 5 mm
      thick neoprene wet suits and either with or without neoprene gloves (5 mm-thick)
      and boots (5 mm-thick) were immersed up to the neck in water at 13 degrees C
      while resting for 3 h or exercising for 2 h. Rectal temperature, oxygen
      consumption and local (chest, back, upper arm, thigh, forearm, calf, hand and
      foot) skin temperatures, skin heat fluxes and thermal insulations were determined
      during immersion. The rectal temperature was not different between conditions but
      the skin temperature was significantly higher with gloves and boots, especially
      at the distal extremities (forearm, calf, hand and foot). Consequently, the core
      to-skin temperature gradient was reduced by wearing gloves and boots, but the
      skin heat loss was markedly increased. Calculated overall body insulation was
      significantly lowered by wearing gloves and boots. These results indicate that in
      wet-suited subjects resting or exercising in cold (13 degrees C) water, gloves
      and boots increase the overall rate of body heat loss. Attenuation of cold
      induced vasoconstriction is proposed as the mechanism.

PMID- 1388403
TI  - [Changes in intracellular pH of working muscle during constant and stepwise
      incremental load exercise].
AB  - In this study, subjects performed wrist flexion in isokinetic manner by using
      CYBEX dynamometer while their right forearm was attached in a MR magnet. 31P-MR
      spectra were obtained from wrist flexor muscles before and throughout the
      exercise. Intracellular pH of muscle was calculated from the chemical shift
      between phosphocreatine (PCr) and inorganic phosphate (Pi). Fifteen Japanese
      males volunteered as subjects. They performed two experimental protocols, i. e.
      constant load test (CT) and stepwise incremental load test (IT). In CT, 10 of the
      subjects were participated. After 2 minutes rest, wrist flexion of 10, 20, 30, 40
      or 50% of maximal voluntary contraction force (MVC) was performed at 2 seconds
      intervals for 15 minutes. In IT, 14 including 9 of CT were participated. They
      performed wrist flexion in incremental contraction force of 5 steps from 10% to
      50% of MVC for 3 minutes in each step. Changes in intracellular pH of muscle
      against contraction level show non-linear relationships both in CT and IT. From
      this relationship we calculated the contraction level at which pH was 6.9
      (%MVC6.9). Mean values of obtained %MVC6.9 by CT and by IT were 29.3 and 30.0% of
      MVC, respectively. And, significant correlation was found between %MVC6.9 by CT
      and by IT. This result shows that %MVC6.9 was a reproducible index independent of
      the type of exercise test, i. e. constant or incremental load test, and might
      reflect the physiological characteristics of the muscle.

PMID- 1388404
TI  - [Stability of body composition in boys and girls 12 through 15 years of age].
AB  - Although underwater weighing has been regarded as a representative of the
      criterion reference methods for determining body composition, this technique is
      cumbersome for screening. The purpose of the present study was to examine the
      stability of body composition assessed not only by underwater weighting but also
      by existing bioelectrical impedance equations and skinfold thickness equations
      during a 4-week period. Ten male and 10 female junior high school pupils, aged 12
      to 15 years, volunteered to serve as subjects. Body density (Db) was estimated by
      underwater weighing (UW), skinfold thickness (ST) method, and bioelectrical
      impedance (BI) method. The UW was considered criterion reference method. The
      underwater weight was the heaviest value that was reproduced twice at least among
      5 to 10 measurements. Residual lung volume was estimated "in water," with the
      subject in the sitting position, by a closed-circuit helium-dilution method. The
      ST equations used for determination of Db were those developed by Nagamine et
      al., while in the BI method equations proposed by Nakadomo et al. were applied.
      The Db for boys by UW did not differ significantly during the 4-week period;
      however, in girls it was significantly lower in the 2nd test (1.0479 +/- 0.018
      g/ml) than in the 1st test (1.0500 +/- 0.019 g/ml). Likewise, the Db estimated by
      ST and BI methods remained unchanged in boys, while in girls it was significantly
      lower in the 2nd test (BI: 1.0445 +/- 0.010 vs. 1.0389 +/- 0.013 g/ml). Test
      retest reliability of all the three methods for measurements conducted 4 weeks
      apart were statistically significant (e.g. UW: r = 0.99, ST: r = 0.94, BI: r =
      0.89 in girls). In conclusion, the validity of Db estimated by these two methods
      was found to be insufficient when absolute values are required. However, body
      composition estimates assessed by ST and BI methods for boys and girls may be
      stable on a relative basis.

PMID- 1388405
TI  - Measurement of regional evaporation rate from skin surface by evaporimeter.
AB  - The present study was conducted to confirm the validity of an evaporimeter and
      its measuring condition prior to applying it to the field of clothing physiology,
      especially for measuring the amount and distribution of the evaporation rate over
      the human body surface. After calibration of the evaporimeter according to the
      manufacture's specification, it was checked for its response time and the
      comparative assessments of the evaporation rate from the skin. The quantitative
      examination of the evaporation rate in both in vitro water loss and in vivo the
      evaporation rate from the human skin, clarified that the observed values of
      evaporation rate were lower than water loss or weight loss of the human body.
      Although the evaporimeter is a useful device to measure the evaporation rate at
      regional parts of the human body under natural condition, an additional
      calibration by an actual in vitro measured water loss should be adopted for the
      accurate assessments of the evaporation rate.

PMID- 1388406
TI  - [Hemispheric differences in letter matching of hiragana and katakana].
AB  - The purpose of the present study was to examine the hemispheric differences in
      letter matching of hiragana and katakana. The stimuli with a pair of each one
      letter of hiragana and katakana were presented unilaterally to the right or left
      visual hemifield with a tachistoscope. The subjects were 40 male right handers.
      They were required to judge whether a pair of letters had the same name or
      different one. A significant right visual hemifield superiority was observed for
      both the accuracy of recognition and reaction time. The results suggest that the
      callosal relay model of Zaidel may be applied to the name matching task.

PMID- 1388407
TI  - Type and amount of environmental information in urban scene--basic study on the
      design of intelligence environment.
AB  - Signs have gained importance as an information mechanism that supports the urban
      activities in signage, and projects are being actively launched in cities. Urban
      spaces are already filled with multitudes of signs including directories and
      signboards, calling for organization of signage as a system and not merely as a
      collection of individual signs. As a first step for tackling with the objectives,
      the present study noted the type and amount of environmental information
      presented in the realm of pedestrians. Our study included (1) investigating the
      type and amount of information available in the streets including underpass; (2)
      classifying and organizing signs according to the content of information; and (3)
      analyzing the relation between different types of information, between situations
      and signs, and continuity of the signs of the same type. The study revealed that
      there was a (1) deviation in information offered at various spots on a pedestrian
      route; (2) multitudes of advertisements and installations other than signs were
      placed at the same spot using the same method as the public signs; and (3) there
      were qualitative lack of signs despite many signs in the investigated area. The
      study thus indicated a need for cross-sectional environmental design for
      information in place of sign designs and delineates several basic requirements
      for it.

PMID- 1388408
TI  - [Development of a new method for calibration of pneumotachograph according to
      flow rate--evaluation of a computer-controlled-system for assessing respiratory
      gas exchange using this method].
AB  - 1) We evaluated the method for calibrating the pneumotachograph according to flow
      rate by the software on personal computer. Flow volume was detected using the
      approximated equation (y = 1.294x2 + 0.989x + 35.824, r = 0.976, p less than
      0.01) from various mean flow rate and integration of output voltage. The error
      between syringe volume (21) and the estimated value on the equation was 10 +/- 8
      ml (0.48 +/- 0.42%). 2) Using the method described in 1), we developed computer
      controlled-system for assessing respiratory gas exchange by mixing chamber
      method. To evaluate the accuracy of the system as compared with the Douglas Bag
      method, we measured the gas parameters of the both methods for two male subjects
      at rest(3 and 5min) and steady state exercise (3 min., 60-240watt). The error
      between the both methods were within +/- 5% in ventilation(VE), mixed expired O2
      (FEO2) and CO2 (FECO2) concentration, and were within +/- 8% in O2 uptake(VO2)
      and CO2 production (VCO2). There were high positive correlation (r greater than
      0.99, p less than 0.01) between the both methods in the all parameters. These
      results indicate that the system in this study would be practical use, that VE
      can be measured in only one pneumotachograph, even if the range of flow rate was
      wide(e.g. from rest to heavy exercise).

PMID- 1388409
TI  - [On the daily living and development of infants living in urban and rural
      regions].
AB  - Temporal pattern of daily living behavior and development in infants aged 3-6 yr
      were compared between urban and rural regions at Fukuoka-prefecture. The present
      study consisted of questionnaire on behavior of daily living and tests for
      development in intelligence and motor function. Rural infants got up and went to
      bed earlier than urban infants. Urban infants with less physical activity were
      inferior to rural infants in motor skill. It is suggested that manual dexterity
      and intelligence may be related.

PMID- 1388410
TI  - [Human body volume measurement by sulfur hexafluorde-dilution method and its
      application to human body composition assessment].
AB  - The absolutely accurate measurement of adiposity in a living organism is
      undoubtedly difficult. Although a number of methods have been developed, none has
      been proven to be both theoretically and empirically an unquestioned validating
      criterion method for the estimation of human body composition. In the present
      study, a new method was introduced that is rapid, safe, and relatively simple to
      administer and has the added advantage of not requiring a measurement of the
      underwater weight. The procedure involves the direct measurement of body volume
      by applying a sulfur hexafluoride (SH)-dilution method with the subject only
      standing in a 375-1 closed chamber (Shimazu BSF-100) that is filled with air and
      0.26 liters of SH. Results indicate that body volume (r = 0.998) and body density
      (r = 0.819) measured by the SH method were highly correlated to those determined
      by underwater weighing. Reproducibility of body volume was found to be almost
      perfect (i.e., 0.995) with the regression coefficient of 1.03 and the intercept
      of -1.5. Variability (CV = 0.7%) in body volume of a 45-year-old reference man
      measured by SH method was very similar to variation (CV = 0.6%) in mass volume of
      the 60-1 prototype. The calculated percent body fat (r = 0.851) and fat-free mass
      (0.962) with some correction of body density were also highly correlated to those
      determined by underwater weighing. We suggest that SH method may be useful for
      assessment of human body composition.

PMID- 1388411
TI  - Thirty years of research on developmental neurolinguistics.
AB  - A body of medically important work has accumulated in the field of developmental
      neurolinguistics in the 30 years since Lenneberg set forth a research agenda for
      that field, consisting of the following: (1) the physiologic specialization or
      endowment for speech; (2) the genetic origin or natural history of vocalization
      and speech; (3) the nature of prelinguistic behavior, making possible the
      detection of any environmental (social) influences; (4) the development of motor
      speech organization from birth; and (5) the limiting effects of deficient
      intelligence, hearing, and environmental stimulation. Subsequent study of these
      questions has established a genetic, neuroanatomic, and functional basis for such
      outwardly disparate disorders as dyslexia, stuttering, autism, and delayed
      language. Studies of emergent motor behavior suggest that babbling may index a
      state of neural maturation favoring expression of spoken languages. Based on
      studies of the congenitally deaf, mentally retarded, and other clinical
      populations it is now considered possible to detect early warning signs of
      developmental language disorders during the first year of life based on analyses
      of vocal turn-taking, gesturing, and utterance complexity.

PMID- 1388412
TI  - Normal values for the two-point discrimination test.
AB  - A 2-point discrimination study was conducted with 112 normal children, ages 2-13
      years. The goal was to determine the age at which children can reliably cooperate
      in performing the 2-point discrimination test and to discover the normal values
      on the fingertips and feet for different ages, as well as to study the changes in
      these values with age. It was found that from age 6 years and older all children
      could perform the test and that discrimination ability improved with age, but was
      only of statistical significance for the feet parameters.

PMID- 1388414
TI  - Hydrosyringomyelia and diastematomyelia detected by MRI in myelomeningocele.
AB  - Magnetic resonance imaging of the spine in 45 patients with myelomeningocele
      revealed hydrosyringomyelia in 24 and diastematomyelia in two. No patient at
      initial imaging manifested symptoms referable to hydrosyringomyelia; both
      patients with diastematomyelia had flaccid lower extremities. One patient
      developed an upper extremity monoparesis which resolved with syringo-peritoneal
      shunt placement; no other patient manifested symptoms or required surgery.
      Ventriculoperitoneal shunt malfunction produced reversible distention of the
      syrinx in another patient who remained asymptomatic.

PMID- 1388413
TI  - Dysmyelinogenesis in animal model of GM1 gangliosidosis.
AB  - Magnetic resonance imaging (MRI), pathologic examinations, and biochemical
      analyses were performed on 2 different canine mutants with GM1 gangliosidosis
      (i.e., English Springer Spaniel and Portuguese Water Dog) and on age- and sex
      matched controls. Serial MRI studies were also performed on a child with
      infantile-onset GM1 gangliosidosis. The affected dogs had abnormalities on MRI,
      including a relative increase in gray matter and an abnormal signal intensity of
      cerebral and cerebellar white matter observed on T2-weighted MRI. White matter
      changes on MRI were similar to white matter abnormalities observed in a 15-month
      old boy with GM1 gangliosidosis. The weight ratio of white to gray matter from
      the frontal lobe was markedly reduced. Microscopic examination revealed
      characteristic ballooned neurons which stained lightly with Luxol-fast blue. The
      central cerebral and cerebellar folia white matter exhibited pallor and gliosis,
      while the corpus callosum and fornix stained normally with Luxol-fast blue. Axons
      appeared intact on Bodian staining. Ultrastructural studies revealed fewer
      myelinated axons in affected puppies. Total gangliosides in gray matter were
      elevated. Thin-layer chromatography demonstrated GM1 ganglioside as the
      predominant ganglioside. The amount of cerebrosides and sulfatides was reduced in
      the gray and white matter when compared to controls but the ratio in gray and
      white matter remained unchanged. Immunostaining of neutral glycolipids disclosed
      increased amounts of stage-specific embryonic antigen-1 glycolipid in gray
      matter. These findings suggest that canine models for GM1 gangliosidosis are
      associated with abnormal myelin development which may be similar to the human
      disease.

PMID- 1388415
TI  - Fragile X positivity in Chinese children with autistic spectrum disorder.
AB  - Chromosome analysis was performed in 105 Chinese children (96 boys, 9 girls) with
      autistic spectrum disorder to assess fragile X positivity. Seventy percent of
      these autistic children were mentally retarded. None of the children in the
      infantile autism group (N = 75) had fragile X positivity. Two boys in the
      autistic condition group (N = 30) had clinical features and chromosomal
      positivity for fragile X syndrome. The low (2%) prevalence rate of fragile X
      positivity in children with different degrees of expressivity of autistic
      features may be related to other factors rather than to pure autistic
      characteristics per se.

PMID- 1388416
TI  - Sleep disorders in Tourette syndrome: a primary or unrelated problem?
AB  - Sleep disturbances are a common complaint in children with either Tourette
      syndrome (TS) or attention-deficit hyperactivity disorder (ADHD). Because a
      significant number of individuals with TS also have ADHD, we attempted to
      determine whether sleep difficulties reported in TS are a primary problem or are
      related to the co-occurrence of ADHD. Using a parent-completed sleep
      questionnaire, data were collected on boys, ages 7-14 years. Three groups, TS
      only (N = 57), ADHD-only (N = 21), and TS+ADHD (N = 89), were compared to an age
      matched control population (N = 146). The complaint of "poor sleep" occurred in
      26% with TS-only, 48% with ADHD-only, and 41% with TS+ADHD; all were
      significantly different from 10% found in controls. Of 19 sleep questionnaire
      items, the incidence of problems occurred statistically more frequently in 5 of
      19 for the TS-only group, in 6 of 19 for the ADHD-only group, and in 17 of 19 for
      the TS+ADHD group. Boys with TS+ADHD had many sleep problems which appeared to be
      related to an arousal disorder. Although the use of medications, especially
      stimulants and anti-depressants, were different between the TS-only and TS+ADHD
      groups, this factor did not account for the large discrepancies in sleep
      disturbance. In boys with TS, sleep problems usually occurred with the co-morbid
      feature ADHD.

PMID- 1388417
TI  - Movement disorders after status epilepticus and other brain injuries.
AB  - A retrospective medical record review was conducted of 173 consecutive children
      hospitalized for acquired brain injuries on a specialized pediatric
      rehabilitation service. The chart review identified children who developed
      movement disorders with acquired brain injuries: 8 with status epilepticus, 2
      with trauma, and 1 with anoxia. Movement disorders were observed more frequently
      following status epilepticus (8 of 12) than following other causes of acquired
      brain injury (3 of 161; P = .0001). Four additional children had severe
      neurologic deficits following status epilepticus but did not develop movement
      disorders. The 11 patients who developed movement disorders had choreiform
      movements predominantly. Even though status epilepticus is a clinical phenomenon
      resulting from a variety of etiologies, the features of movement disorders in
      these children were strikingly similar. The pathophysiology of this complication
      is unknown.

PMID- 1388418
TI  - Clinical features for prediction of survival in neonatal muscle disease.
AB  - Review of 17 newborns with muscle disease demonstrated that clinical features
      associated with survival beyond 1 year of age included gestational age of at
      least 35 weeks and requirement of mechanical ventilation for less than 21 days.
      In contrast, poor outcome was associated with Apgar scores below 5 at 5 min,
      pulmonary complications, arthrogryposis, or other congenital anomalies. The
      incidence of decreased fetal movements, polyhydramnios, hypotonia, and assisted
      delivery was not statistically different between infants who died early and those
      who survived beyond 1 year of age. Clinical features of newborns with muscle
      disease may be useful for prediction of outcome, especially when muscle biopsy
      abnormalities are nonspecific.

PMID- 1388419
TI  - Bilateral periodic lateralized epileptiform discharges in Mycoplasma
      encephalitis.
AB  - Status epilepticus and prolonged coma developed in two patients with respiratory
      tract infections caused by Mycoplasma pneumoniae. Serial electroencephalography
      initially revealed bilateral, independent, periodic, lateralized epileptiform
      discharges. This pattern was replaced several days later by other
      electroencephalographic abnormalities.

PMID- 1388420
TI  - Comparison of MRI white matter changes with neuropsychologic impairment in
      Cockayne syndrome.
AB  - The neuropsychologic function and white matter changes observed on magnetic
      resonance imaging (MRI) in Cockayne syndrome were studied. MRI with T2-weighted
      sequences revealed periventricular hyperintensity and white matter hyperintensity
      in all 3 Cockayne syndrome patients examined; in contrast, 8 age-matched controls
      had no periventricular or white matter hyperintensity. MRI scans were graded
      according to the severity of periventricular or white matter hyperintensity using
      a scale applied to an elderly patient population. There was no difference in the
      severity of MRI white matter changes in these 3 Cockayne syndrome patients, 2 of
      whom had severe neuropsychologic functions and one a relatively milder one. There
      was no correlation between neuropsychologic impairment and MRI white matter
      changes.

PMID- 1388421
TI  - Developmental bilateral perisylvian dysplasia.
AB  - Acquired bilateral anterior opercular lesions result in the characteristic Foix
      Chavany-Marie syndrome that features expressive dysphasia and pseudobulbar palsy.
      A developmental congenital variant that represents a restricted disorder of
      neuronal migration was recently reported. We report a newborn with autopsy
      confirmed developmental bilateral perisylvian dysplasia. Polymicrogyria was found
      on detailed histologic study confirming the only prior pathologic study of this
      syndrome. The clinical heterogeneity of this disorder with neonatal and childhood
      modes of presentation is reviewed. Speculation regarding pathogenesis focuses on
      either a genetically determined selective aberration of neuronal migration or an
      in utero postmigration vascular accident.

PMID- 1388422
TI  - Transient oculomotor nerve paresis in congenital distal basilar artery aneurysm.
AB  - The clinical and pathologic findings of a 10-month-old girl with congenital heart
      disease who died after rupture of a congenital distal basilar artery aneurysm are
      reported. The patient developed transient minimal oculomotor nerve paresis 7 days
      prior to suffering a massive subarachnoid hemorrhage. The finding of transient
      third nerve dysfunction, particularly in the context of recurrent syncope, should
      prompt investigation for an intracranial arterial aneurysm.

PMID- 1388423
TI  - Agenesis of corpus callosum and intraventricular lipomas.
AB  - Intracranial lipomas are rare and usually do not have clinical expression. They
      are located most commonly in the interhemispheric fissure and may also be found
      in the quadrigeminal, ambient, chiasmatic, interpeduncular, sylvian, and
      perimesencephalic cisterns. Interhemispheric lipomas may be associated with
      choroid plexus lipomas. The ultrasonography, computed tomography, and magnetic
      resonance imaging findings are reported in a neonate with lateral ventricular
      choroid plexus lipomas and interhemispheric lipoma associated with agenesis of
      the corpus callosum.

PMID- 1388424
TI  - Phenotypic Duchenne muscular dystrophy with C-terminal domain.
AB  - We report a patient with X-linked muscular dystrophy who had rapidly progressive
      muscle weakness and became wheelchair-bound at age 10 years. Clinically, he was
      diagnosed as having Duchenne muscular dystrophy; however, he was diagnosed as
      having Becker muscular dystrophy by dystrophin tests using a C-terminal
      monoclonal antibody. No immunolabelling was observed with a monoclonal antibody
      against the N-terminal domain. Multiplex polymerase chain reaction analysis
      revealed the deletion of exons 3-19. The data suggest that the deletion of the N
      terminal domain of dystrophin can cause a severe phenotype even when the C
      terminus of the protein is well preserved.

PMID- 1388425
TI  - Congestive heart failure and cardiac thrombus as first presentations of
      Friedreich ataxia.
AB  - The majority of patients with Friedreich ataxia present with gait ataxia.
      Congestive heart failure usually is a terminal event. We report a 9-year-old boy
      who developed congestive heart failure and thrombus formation in the left
      ventricle at age 5 years and then progressive ataxia as well as other features of
      Friedreich ataxia; therefore, congestive heart failure and thrombus formation may
      rarely be the initial findings in Friedreich ataxia.

PMID- 1388426
TI  - Congenital ceroid-lipofuscinosis.

PMID- 1388427
TI  - Obstetric ultrasound--an issue of quality.

PMID- 1388428
TI  - Who should perform sonograms? Those with the skills and experience to provide
      complete and accurate service.

PMID- 1388430
TI  - Can we expect greater intelligence from human milk feedings?

PMID- 1388429
TI  - How do you give the bad news to parents?

PMID- 1388431
TI  - Many benefits associated with mother's laboring in water.

PMID- 1388432
TI  - On circumcision.

PMID- 1388433
TI  - Warm tub bath after spontaneous rupture of the membranes.
AB  - Increasing numbers of pregnant women take a warm bath during labor. Yet few
      evaluations have addressed benefits claimed and possible risks of this practice.
      Using retrospective data from a continuing trial at a birth center in Stockholm,
      we compared 89 women who took a warm bath after spontaneous rupture of the
      membranes at term with 89 women who had the same interval from spontaneous
      membrane rupture to delivery and who did not bathe. No statistical difference was
      observed between the groups with respect to infections, asphyxia or respiratory
      problems in the newborn infant, or maternal signs of amnionitis. However, a
      tendency toward more complications was observed in the bathing group. Babies born
      more than 24 hours after rupture of membranes had significantly lower Apgar
      scores at 5 minutes in the bathing group than in the control group. As a result
      of our review of the sparse literature on this practice and the data from this
      study, we have modified the bathing policy at the birth center from a rather
      enthusiastic to a more cautious approach. Recommendations about the use of a warm
      bath in labor will require further investigation, such as randomized trials with
      large numbers of subjects.

PMID- 1388434
TI  - Just another day in a woman's life? Part II: Nature and consistency of women's
      long-term memories of their first birth experiences.
AB  - Twenty women who attended the author's natural childbirth classes between 1968
      and 1974 were the informants in this study of long-term memories of their first
      childbirths. The data from each informant consisted of 1) a labor and birth
      questionnaire, including an open-ended account of her labor, written shortly
      after her baby was born; 2) a similar questionnaire and account written in 1988
      and 1989; and 3) a transcribed interview during which her memories and
      perceptions were discussed and any discrepancies between the questionnaires were
      explored. The questionnaires were compared for consistency of recall, and the
      interviews consulted for further clarification. Specific memories were excerpted,
      compared, classified, tabulated, and summarized. Findings were that, years later,
      women's memories are generally accurate, and many are strikingly vivid,
      especially of onset of labor; rupture of the membranes; arrival at the hospital;
      actions of doctors, nurses, and partners; particular interventions; the birth;
      and first contact with the baby. Most memory lapses or confusion were minor.
      Evidence of a halo effect was observed as well.

PMID- 1388435
TI  - The crisis of pregnancy loss: a team approach to support.
AB  - When a pregnancy loss occurs, a woman and her family may require help to
      facilitate grieving. Several support strategies can be recommended. We
      established a volunteer, hospital-based perinatal crisis support group that
      provides intervention, assists clients in moving through the period of
      disorganization, and offers information and support. Four examples illustrate the
      work of the group and its collaboration with personnel in other departments and
      agencies. Guidelines are provided for the establishment of a support team.

PMID- 1388436
TI  - Providing versus packaging support for bereaved parents after perinatal loss.

PMID- 1388437
TI  - Obstetric ultrasound: who should perform sonograms?
AB  - Obstetric ultrasound has revolutionized clinical practice by expanding knowledge
      of fetal growth, physiology, and behavior, and allowing the fetus to emerge as a
      treatable patient. This dramatic change in clinical practice has not been
      accompanied by a growth in education or guidelines for the performance of
      ultrasound studies. This article reviews some of the many professional issues
      that are still unresolved, such as education, level of care providers, office
      versus hospital scanning sites, level of ultrasound study, legal issues,
      obstetrics versus radiology as appropriate specialties to perform sonograms, and
      implications affecting childbearing women, based on concern for quality care of
      mothers and babies.

PMID- 1388438
TI  - Improving pregnancy outcomes: public versus private care for urban, low-income
      women.
AB  - This study describes the characteristics of women who received maternity care
      from the Chicago Department of Health or from private practitioners in 1988 and
      the first half of 1989, and who delivered at the University of Illinois Hospital
      or Cook County Hospital. The risk of preterm low birthweight for the infants of
      these women was compared according to source of prenatal care. The likelihood of
      giving birth to a preterm, low-birthweight infant was significantly greater (odds
      ratio 3.1, 95% confidence interval 2.3-4.0) for women who received care only from
      private physicians (n = 530) compared with those who received care entirely from
      the Chicago Department of Health (n = 2465). This relationship remained after
      adjustment for race, age, parity, history of adverse pregnancy outcomes, smoking,
      and use of drugs during pregnancy. We examined alternative explanations for these
      findings, and concluded that although the role of urban public health departments
      in the direct delivery of maternity care services continues to be a source of
      controversy, these institutions remain an important provider of such care for low
      income women.

PMID- 1388439
TI  - Treatment and outcomes of psychotic patients during pregnancy and childbirth.
AB  - This study examined whether particular groups of psychotic women are likely to
      present management problems during pregnancy and childbirth. The pregnancy
      courses and outcomes of 22 psychiatric inpatients were reviewed. Schizophrenic
      women with delusions or psychotic denial about the pregnancy were significantly
      less likely to detect labor than were nondelusional women. Ability to detect
      signs of labor and cooperate with labor instructions was significantly more
      likely in women with bipolar affective disorders than in those with schizophrenic
      disorders, and was also more likely in those women with severe personality
      disorders and substance abuse histories. The total patient cohort underwent
      significantly more cesarean sections than their nonpsychiatric counterparts who
      delivered at the same hospital. These findings suggest that psychotic women are
      at high risk for the development of pregnancy and birth complications.

PMID- 1388440
TI  - Nausea and vomiting during pregnancy: effects on the quality of women's lives.
AB  - More than 70 percent of all pregnant women experience nausea and vomiting during
      pregnancy, and 28 percent report that symptoms cause them to change their usual
      activities. We investigated the magnitude of problems that nausea and vomiting
      impose on the lifestyle of pregnant women and their families. Twenty-seven women
      who were experiencing different degrees of nausea and vomiting were selected from
      147 pregnant women and asked to participate in semistructured telephone
      interviews. All participants reported changes in family, social, or occupational
      functioning as a result of these symptoms. Nausea and vomiting can impose
      substantial lifestyle limitations on pregnant women that can have short- and long
      term consequences for them and their families. Both the duration and severity of
      symptoms were greater for many participants than is generally believed. All
      participants reported that recumbent rest or dietary alterations provided relief.
      Caregivers should recognize and validate the need for pregnant women to make
      changes in lifestyle that will enable them to achieve comfort.

PMID- 1388441
TI  - Hmong women: characteristics and birth outcomes, 1990.
AB  - Current demographic characteristics and pregnancy outcomes of immigrant Hmong
      women in a small town in southeastern United States were documented in a
      retrospective study. Interviews and review of existing records were used to
      determine prenatal practices and perceived problems. Sixteen health professionals
      and two women from the community were interviewed, and the labor and delivery
      records from 1985 to 1990 were reviewed for parity, child spacing, and health
      status of the women and newborns. The greatest concerns voiced by health
      caregivers were multiparity and the need for contraceptive compliance. Seventy
      eight full-term infants were born to 64 women in five years, with 2 stillbirths.
      No eclampsia, diabetes, or Rh incompatibilities were noted. Evidence is limited
      that birth frequency or outcome for Hmong women is a problem. Their perinatal
      difficulties were thought to be sociocultural rather than medical. Further study
      of the effects of acculturation on maternal family position, perinatal risks, and
      birth outcomes is imperative as lifestyle and environment change for these
      immigrant women.

PMID- 1388442
TI  - Case report: survival of an infant with a birthweight of 345 grams.
AB  - Infant survival with ever-decreasing birthweights is attainable with recent
      advances in maternal-fetal medicine and enhanced neonatal intensive care. We
      report a gestation complicated by severe chronic hypertension and fetal distress
      necessitating delivery at 26 1/7 weeks. The growth-retarded newborn weighted 345
      g (12 oz) and survived with minimal sequelae despite a protracted and complicated
      neonatal course.

PMID- 1388443
TI  - Roundtable: survival and outcome of the extremely low-birthweight infant.

PMID- 1388444
TI  - Letter from England: a strong step forward for maternity services.

PMID- 1388445
TI  - Unresolved controversies: home uterine activity monitoring.

PMID- 1388446
TI  - Doulas and the quality of maternity services.

PMID- 1388447
TI  - Immunohistochemical analysis of the basal forebrain in Alzheimer's disease.
AB  - An immunohistochemical analysis utilizing antibodies to glial fibrillary acid
      protein (GFAP), microglia, beta-amyloid, amyloid P-component, neurofibrillary
      tangles (NFT), and microtubule associated protein-tau (MAP-tau) was performed on
      the cholinergic basal forebrain in Alzheimer's disease (AD). This severely
      compromised system, which includes the nucleus basalis of Meynert, is largely
      responsible for the massive loss of cortical and subcortical cholinergic
      innervation in the diseased state. Our study juxtaposes the basal forebrain
      immunohistopathology to the hippocampus, amygdala, and entorhinal cortex in AD.
      Key findings include a progressive degeneration of these cholinergic neurons
      characterized by the formation of immunoreactively atypical NFT, the loss of
      intraneuronal lipofuscin, a lack of senile plaque and beta-amyloid deposition
      within the basal forebrain, and end-stage gliosis without residual extracellular
      NFT. These structural and compositional differences suggest a unique pathogenesis
      of the basal forebrain separate from other cortical regions in AD.

PMID- 1388448
TI  - Early clinical neurochemistry of CNS-active drugs. Chloral hydrate.
AB  - Chloral hydrate was introduced into therapeutics more than 120 years ago, and
      soon became popular as a somnifacient. It is the first synthetic CNS depressant.
      Its metabolite, urochloralic acid, was detected early. Studies of the biochemical
      pharmacology of chloral hydrate have engaged the attention of many investigators
      in succeeding years. Its mode of action in producing sleep was initially
      attributed to the possibility that it gives rise to chloroform in vivo. Although
      this hypothesis did not stand up to scientific scrutiny, it led to efforts to
      establish how chloral hydrate brings about its action. This seems to be through
      its reduced metabolite, trichloroethanol. The precise mode of action on the
      nervous system remains to be worked out.

PMID- 1388449
TI  - Debrisoquine metabolism in Chinese patients with Alzheimer's and Parkinson's
      diseases.
AB  - We determined the oxidative phenotype and metabolic ratio of debrisoquine in 96
      Chinese patients with Alzheimer's disease (n = 12), Parkinson's disease (n = 55),
      and using patients with stroke and cervical spondylosis as controls (n = 29). We
      did not find any difference in debrisoquine metabolic phenotype among Parkinson's
      disease, Alzheimer's disease, and control patients as judged by chi-square
      analysis. In addition, the metabolic ratio of all our patients was less than
      12.6. The result suggested that Chinese patients with Parkinson's disease and
      Alzheimer's disease metabolize debrisoquine at a velocity not different from that
      of their Western counterparts even though the frequency distribution of
      debrisoquine metabolism phenotyping in these two populations is quite different.

PMID- 1388450
TI  - Decapitation ischemia-induced release of free fatty acids in mouse brain.
      Relationship with diacylglycerols and lysophospholipids.
AB  - In this study, the release of lysophospholipids (to depict phospholipase A2
      activity) and diacylglycerols (DG) (to depict stimulated hydrolysis of
      polyphosphoinositides) was related to the decapitation-induced release of free
      fatty acid (FFA) in the mouse brain. To assay for lysophospholipids, Balb/c mice
      were injected intracerebrally with either [3H]choline or [3H]inositol for 16 h in
      order to label their respective phospholipids. These lipids were examined at
      various times (30 s to 30.5 min) after decapitation. Between 30 s and 1.5 min
      after decapitation, the rate of FFA release (3 micrograms FA/mg FA in
      phospholipids/min) was three times more rapid than that between 10 and 15 min
      (0.8 microgram FA/mg FA in phospholipids/min). FFA released during the initial
      phase were enriched in 20:4 and 18:0 whereas those released during the latter
      phase were nonspecific. The DG fatty acids are enriched in 18:0 and 20:4.
      Ischemia induced a rapid release of DG as measured by its fatty acid content (3.2
      micrograms FA/mg FA in phospholipids/min). Unlike FFA, the level of DG reached a
      plateau after 1.5 min and remained elevated for the entire 30.5 min. In agreement
      with previous notions indicating the involvement of phospholipase A2 in ischemic
      insult, steady increases in radioactivity of both lysophosphatidylcholines and
      lysophosphatidylinositols were observed with time after decapitation. Based on
      the preferential increase in both 18:0 and 20:4 during the initial time period,
      the results suggest that poly-PI hydrolysis coupled to DG-lipase may contribute
      to the initial release of FFA, whereas the FFA released subsequent to the initial
      phase may be mainly a result of activation of phospholipase A2 acting on
      phosphatidylcholines and phosphatidylinositols.

PMID- 1388451
TI  - Aluminum-induced acute cholinergic neurotoxicity in rat.
AB  - In the present study the acute effect of intravenous aluminum chloride (1 mg/kg)
      on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities of
      rats was investigated. Aluminum was found to cross the blood-brain barrier (BBB)
      as indicated by the detection of aluminum in the cerebrospinal fluid (CSF) 30 min
      after femoral vein injection. Two hours following aluminum injection, ChAT
      activity in the basal forebrain and hippocampus was significantly reduced by 30%
      and 22%, respectively, whereas no change was observed in the caudate nuclei. On
      the other hand, AChE activity was significantly increased by 45% in the caudate
      nuclei, whereas little change was observed in other brain areas. This report
      demonstrates that rapid transport of Al across the BBB, and the acute nature of
      Al neurotoxicity in rats.

PMID- 1388452
TI  - The effects of beraprost Na, a stable prostacyclin analog, on animal models of
      stroke.
AB  - We evaluated the effects of beraprost Na (Sodium (+-)-(1R*,2R*, 3aS*,8bS*)
      2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3- hyd roxy-4-methyl-1- octen-6-ynyl]
      1H-cyclopenta[b]benzofuran-5-butylate, beraprost), a stable and orally active
      prostacyclin (PGI2) analog with potent antiplatelet and vasodilating properties,
      on two stroke models, namely sudden death induced by arachidonate (AA) in rabbits
      and spontaneous stroke in stroke-prone spontaneously hypertensive rats (SHRSP).
      In the AA-induced sudden death model, 30 min after beraprost administration (1 or
      3 mg/kg, po), AA was injected into the rabbit internal carotid artery, and
      incidence of convulsion and sudden death were assessed. Beraprost decreased both
      incidence of convulsion and mortality of rabbits. In SHRSP, orally administered
      beraprost (100 micrograms/kg, twice a day from 56-385 d of age) improved survival
      rate and decreased incidence of stroke. Preventive effects of beraprost on the
      two stroke models may have been caused mainly by the improvement of cerebral
      circulation. These results indicate that beraprost may have potential in the
      treatment and/or prevention of the cerebral circulatory disorders.

PMID- 1388453
TI  - [Salamanca University: a historic outline].

PMID- 1388454
TI  - [Nursing: a profession in crisis].

PMID- 1388455
TI  - [The right of the patient to be "left alone"].

PMID- 1388456
TI  - [Morphologic substrates of the ventricular route of secretion and transport of
      substances in the tubero-infundibular region of the hypothalamus. Ultrastructural
      study].
AB  - Ultrastructural studies of the ependyma of the tuberoinfundibular region of the
      rat hypothalamus have revealed the existence of intraventricular axonal endings
      and of cytoplasmic blebs and bulbs that project from the apical surface of the
      ependymal cells to the ventricular lumen. All these structures account for the
      processes of ependymal apocrine secretion and the neuroventriculocrinia, and
      hence the release of biologically active substances into the cerebrospinal fluid
      (CSF). These substances contained in the CSF must act on the nervous nuclei of
      the tuberoinfundibular region, such as the arcuate nucleus, which is very
      important in the neuroendocrine regulation of the anterior pituitary gland.
      Dilated intercellular spaces among neighbouring ependymocytes of this region,
      small intraependymal cisternae and, in particular, a lateral prolongation of the
      infundibular recess, which courses through the nervous tissue between the arcuate
      nucleus and the median eminence from the vertex of the lateral angle of the
      infundibular recess, may be the route followed by the CSF from the third
      ventricle to the tissue compartment of the tuberoinfundibular region. Also
      studied are the cisternae of the region and the relationships of these with the
      lateral prolongation of the infundibular recess. Some of these cisternae may be
      filled by the CSF through the prolongation. In this way, the tissue compartment
      of CSF would be enlarged, and hence the ventricular route for the secretion and
      transport of biologically active substances would be potentiated.

PMID- 1388457
TI  - Immunocytochemical study of vasopressin-like immunoreactive material in the
      gastrointestinal tract of the hedgehog Erinanceus europeus.
AB  - A study was made of portions of the gastrointestinal tract including the stomach,
      duodenum, jejunum, ileum, colon and rectum, and the hypothalamus of hedgehogs
      using the peroxidase-antiperoxidase (PAP) method incubating paraffin embedded
      sections of 6-7 microns thickness in an anti-arginine-vasopressin serum at a
      dilution of 1:1000. Vasopressin-like immunoreactivity is present in cells of the
      epithelial layer of the intestinal mucosa ranging from the stomach to the rectum.
      In the stomach the numbers of these cells are very small although they increase
      in the small intestine. However, in the different portions of this latter organ
      no significant differences can be found. Both, in colon and rectum there are
      cells with vasopressin-like immunoreactive material although at higher
      concentrations than in the rest of the gastrointestinal (GI) tract.
      Immunoreactive material is present throughout the epithelial layer of the mucosa
      and in general the cells of the mucosa are of the open kind. Using the same
      antiserum and at similar dilution, both cells and nerve fibres containing
      vasopressin-like immunoreactivity were observed in hypothalamic sections of this
      animal species and were used as positive controls. It is concluded that in the
      gastrointestinal (GI) tract of the hedgehog there is a population of epithelial
      cells that contain a immunoreactivity vasopressin-like-peptide (referred to as
      vasopressin-like peptide (AV-LP) whose numbers increase in the distal sense.

PMID- 1388458
TI  - [The use of silicone breast prosthesis in Puerto Rico].
AB  - To obtain data on the use of gel-filled silicone breast implants in Puerto Rico,
      a study was undertaken by the Division of Plastic Surgery of the University of
      Puerto Rico. Questionnaires, designed to obtain information about their breast
      implant patients, were mailed to the 22 plastic surgeons in Puerto Rico. Sixty
      eight percent of the plastic surgeons responded. The collected data showed that
      1,682 patients received gel-filled silicone breast implants, of whom breast
      augmentation accounted for 82%, and post-mastectomy reconstruction for 18%.
      Capsular contracture occurred in 16% and early complications in 2.5% of the
      patients. Autoimmune disease was rare (.0006%), as was breast cancer (.0002%).
      Very few patients in Puerto Rico received polyurethane foam covered breast
      implants (.005%). The risk of problems associated with breast implants in our
      Island appears to be very low.

PMID- 1388459
TI  - Asymptomatic carcinoma of the endometrium in a patient on adjunctive tamoxifen
      therapy for carcinoma of the breast.
AB  - A case report of a 70 years old female, on tamoxifen for over five (5) years
      after a left mastectomy and with lymphadenectomy and radiotherapy in whom an
      asymptomatic adenocarcinoma of the endometrium is reported. Review of the
      literature suggests this association, however, definitive proof that tamoxifen
      causes cancer of endometrium has not been fully accepted. The best study in this
      regards is the one from Radiohemmet Oncologic Centre from Stockholm, Sweden.
      Patients with cancer of the breast that have been over two (2) years on tamoxifen
      should be screened with endovaginal sonograms for thickness of endometrium,
      thickness over 9mm and possibly over 5mm should be investigated with hysteroscopy
      and fractional uterine curetage.

PMID- 1388460
TI  - [Exercise, physical activity and diabetes mellitus].
AB  - Vigorous regular exercise is a recommended inclusion in the management of
      diabetes of persons with diabetes of both types, regardless of age. Benefits can
      be identified in the physiological (improved cardiovascular fitness, flexibility
      and muscle toning; in the metabolic and hormonal processes for energy
      production), as well as psychosocial realms (self-esteem, stress management,
      socialization opportunities). Considerations of the risks (hyper or hypoglicemia,
      ketoacidosis, neuropathies or complications os cardiac risks), and
      contraindications (unplanned weight training in cases with proliferative
      retinopathy, hypertension, uncontrolled diabetes) must be part of the exercise
      prescription and implemmentation. Exercise programs must be fun, varied and
      comply with exercise physiology principles such as gradual progression in
      intensity or target heart rate, recommended frequency and duration, regular
      hydration, and warm-ups and cooling routines. Regular vigorous physical
      education, sports, regular exercise and active recreational activities can be
      part of a healthy lifestyle of persons with diabetes.

PMID- 1388461
TI  - [Midfacial degloving: an alternative approach to the frontobasal area, the nasal
      cavity and the paranasal sinuses].
AB  - Midfacial degloving can be characterized as an alternative surgical approach for
      exposing the bony structures of the midface. In combination with transient
      partial osteotomies the nasal cavities, the paranasal sinuses, the
      pterygopalatine fossa and the posterior parts of the anterior skull base are
      easily accessible. Using an intercartilaginous, a transseptal and a
      circumvestibular incision in the nose and a vestibular incision in the oral
      cavity the soft tissues of the upper face are mobilized and transposed cranially
      up to the infraorbital rim, the nasion and the lacrimal sac. Thus one can avoid
      scar formations in the face. In comparison with the common visible incisions in
      the face a bilateral exposure of midline structures is possible. The resected
      bone can be easily replaced and fixed with titanium miniplates for
      osteosynthesis. The soft tissue glove is replaced. A correct suture technique for
      readaptation especially in the nasal cavity is most important to avoid a circular
      stenosis of the nasal aperture. Between 1986 and 1991, 40 patients with various
      tumors (juvenile angiofibroma, inverted papilloma, esthesioneuroblastoma,
      squamous cell carcinoma of the maxillary sinus, benign tumors of the
      pterygopalatine fossa, clivus chordoma) underwent this procedure. Neoplasms and
      fractures of the anterior frontal skull base, the frontal sinus, the orbital
      cavity and the zygoma were less accessible due to the unsatisfactory exposure of
      these regions. Complications and side effects were rare. In five cases, a
      transient paresthesia of the infraorbital nerve and a facial edema were observed.
      In one case, a circular stenosis of the nasal aperture required a second plastic
      procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388462
TI  - [Treatment of hemangioma with the neodymium:yttrium-aluminum-garnet laser (Nd:YAG
      laser)].
AB  - Laser therapy and in particular Nd:YAG laser therapy has become of increasing
      importance amongst the various methods of treating haemangiomas. Nd:YAG laser
      radiation penetrates deep into the tissue. To avoid undesirable results of
      treatment, certain treatment guidelines must be observed: to protect the tissue
      from serious heat damage, the Nd:YAG laser radiation should be applied
      exclusively with simultaneous tissue cooling. Depending on the location of the
      haemangioma, this is carried out with ice cubes (if possible, not containing air
      bubbles) or with an ice-cold Ringer solution. The depth of penetration of the
      laser radiation can be increased by tissue compression with a piece of ice or
      with a special glass disc. In very voluminous haemangiomas, the laser light is
      additionally applied via a bare fibre directly on to the vascular tissue. The
      laser power densities we use are between 500 and 3,000 watts/cm2. The power
      chosen depends on the tissue effect of the laser radiation. Blanching of the
      vascular tissue without carbonisation is aimed at. With consistent observance of
      the treatment guidelines specified, haemangiomas should be treated as early as
      possible with the Nd:YAG laser. The treatment principle of "wait and see" is
      often advocated, but we consider to be obsolete, since cosmetically and
      functionally unsatisfactory residual scars may remain even after complete
      haemangioma regression. Moreover, the progressive haemangiomas which often lead
      to complications cannot be distinguished from regressive haemangiomas. Last but
      not least, the child and the parents should be spared the (in some cases
      appreciable) psychological strain of a haemangioma.

PMID- 1388463
TI  - [Rhinoplasty: preventable errors in the first 100 interventions and secondary
      correction].
AB  - The most frequent avoidable mistakes which a young rhinosurgeon commits concern
      the analysis of the patient's desire, the preoperative critical examination of
      the facial proportions, the choice of the surgical technique and the operative
      approach, the choice of the implantation material and the method of how to
      implant it in a form-fitting manner, overreductions or underreductions by
      osteotomy and mistakes in the course of postoperative change of the dressings.
      The way of avoiding these errors and the way of their secondary correction are
      presented. The principle of a secondary operation is a structural reorientation
      by a few minor surgical steps.

PMID- 1388464
TI  - [The acoustics of the open mastoid cavity (so-called "radical cavity) and its
      modification by surgical measures. I. Physical principles, experimental studies].
AB  - Up to now the importance of the outer ear for the sound transmission is nearly
      neglected in the otosurgical literature. Nevertheless, surgical procedures can
      cause severe alterations in the anatomy of the outer ear channel. Necessarily
      variables which take influence on the acoustic behaviour of the outer ear can get
      changed by these surgical manipulations. By means of in-situ measurements of the
      sound-pressure-level near the tympanic membrane the influence of the ear
      channel/mastoid cavity volume as well as of the size of the outer meatus on the
      resonance frequency is investigated. In a model of variable volume and several
      sizes of outer meatus there can be found that the course of resonance-caused
      sound-pressure augmentation depends on two determining factors: due to the
      physical-acoustical conditions (Helmholtz-resonator) the peak of the resonance
      caused augmentation shifts to lower frequencies the smaller the outer meatus and
      the larger the volume of the channel/mastoid cavity. Viceversa, an augmentation
      of the external meatus and an obliteration of the cavity causes a higher
      resonance frequency. Within values for the volume and the meatal size as can be
      found in radical cavity surgery the resonance frequency varies in a wide range
      from 1260 up to 3175 Hz. There is no substantial influence on the amplitude of
      the sound-pressure augmentation. Measurements undertaken in a temporal bone
      specimen underline these results: as well as in the model alterations of cavity
      volume and meatal size lead to partial extensive shiftings of the resonance
      frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388465
TI  - [Effect of decreased and lost high frequency hearing on latency of acoustically
      evoked brain stem reaction].
AB  - The diagnosis of retrocochlear damage is supported by an increased latency
      difference between peak I and peak V. In case of high frequency hearing loss peak
      I is often hard to determine, and peak V latency may be shifted not only by
      neural delay, but also by missing basal hair cells. The amount of cochlear delay
      can be estimated by a procedure presented here. High frequency decay was
      simulated by steep high-pass noise masking. Peak V latency turned out to be
      established by the highest unaffected frequency components of the click stimulus.
      Thus, in case of a high frequency gap (with normalization towards higher
      frequencies) latency may be almost normal. In case of prolonged latency the
      amount ascribable to the cochlea may be rather precisely be estimated. If the
      whole lag is explained this way, unnecessary further diagnostics can be avoided.

PMID- 1388466
TI  - [The ototoxicity of the cytostatic drug carboplatin in patients with head-neck
      tumors].
AB  - The side effects of the anti-cancer drug carboplatin on the cochlea in 65
      patients with head and neck cancer were examined in the present study. A possible
      dependence of ototoxicity on the patient's age, the effect of pre-existing
      audiometric changes and the carboplatin dose were investigated. A therapy-induced
      sensory hearing loss was found in 32% of the patients. The average hearing loss
      was 15 dB and primarily involved the frequency ranges from 4 to 8 kHz. The degree
      of the hearing defects incurred was not influenced by the patient's age or pre
      existing hearing defects but depended on the carboplatin dose used. The severity
      of carboplatin cochlear ototoxicity was moderate, so that no patient suffered a
      lack of hearing that was of social significance.

PMID- 1388467
TI  - [Voice rehabilitation after laryngectomy with voice prostheses. Results of a
      prospective follow-up study].
AB  - Although the results of surgical rehabilitation by means of voice prostheses are
      on the average better than rehabilitation via oesophageal speech, the
      tracheoesophageal puncture (TEP)-technique has so far not been widely used in
      Germany. The majority of hospitals still prefer the "traditional" method of voice
      rehabilitation using oesophageal speech. The present prospective study was
      undertaken to compare the results of postlaryngectomy vocal rehabilitation, if
      patients were offered the surgical voice rehabilitation via voice prosthesis as
      an alternative to oesophageal speech. Taking into account all the patients who
      underwent laryngectomy from 1989 until 1990 in Tubingen, primary surgical voice
      rehabilitation was performed in 44 out of 54 patients (81.5%). Interestingly
      enough, 34 patients who underwent laryngectomy were able to perform communication
      via the telephone on the day of their discharge. Moreover, one-third of the
      laryngectomised patients showed a significant increase in speech intelligibility
      within the first six months after laryngectomy. 36 patients with laryngectomy
      were able to attain proficiency 6 months after surgery. In 12 patients the
      prosthesis had to be removed, since either phonation was impossible or patients
      successfully learned and preferred oesophageal speech. In conclusion, independent
      of the method of voice rehabilitation (prosthesis, electrolarynx, oesophageal
      speech), our results support the hypothesis that a voice rehabilitation regimen
      will yield a higher rehabilitation rate of patients if rehabilitation via
      surgical voice is offered as an alternative to learning the oesophageal voice.
      Therefore, it seems to be advisable that patients are allowed to have the choice
      between surgical rehabilitation and oesophageal speech restoration.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1388468
TI  - [Malignant oncocytoma of the submandibular gland].
AB  - Case report on a malignant oncocytoma of the glandula submandibularis in a 56
      year old female patient. Oncocytomas in otorhinolaryngology are very rare, mostly
      benign tumours appearing mainly in women between 60 and 90 years of age. They
      comprise oncocytes, which are epithelial cells with abnormally formed cytoplasm.
      Oncocytes have an acidophilic granular cytoplasm. Electron microscopy reveals a
      pronounced increase of hypertrophic mitochondria. Besides the benign variants
      there are also rare cases of malignant forms. Therapy consists of surgical
      resection.

PMID- 1388470
TI  - [Tracheotomy and dilatation of the stenosis as alternative methods of treatment].

PMID- 1388469
TI  - [The rare case--neurilemmoma of the vocal cord].
AB  - We present the case of a neurilemmoma of the vocal cord, which is a very rare
      tumour at this site. The tumour was completely removed by microlaryngoscopy. The
      78-year old female is free of recurrence for 1 year. She does not show any sign
      of neurofibromatosis. Microscopic features and the literature are reviewed.

PMID- 1388471
TI  - [Recommendations for an operation to improve nasal respiration].

PMID- 1388472
TI  - [Comment on the article, "Topics in expert testimony"].

PMID- 1388473
TI  - [Magnetic resonance tomography in questionable lesions of the ENT area.
      Examination technique and results of a prospective study of 1,493 patients].
AB  - 1493 patients with various lesions in the head and neck region were prospectively
      evaluated with MR imaging (MRI) and other imaging modalities. The findings of MRI
      and conventional imaging techniques were correlated with histological findings.
      All MRI examinations were carried out on a 1.0 and 1.5 Tesla superconducting MR
      unit employing combined T1 and T2 weighed spin-echo sequences. Dynamic MRI with
      fast gradient-echo sequences and application of a paramagnetic contrast agent (Gd
      DTPA) was additionally performed in 120 patients. 250 patients were examined with
      non-invasive MR angiography. Appropriate saturation enabled the visualization of
      either arterial or venous vascular structures. Analysis of metabolic parameters
      and tumor proliferation was possible through in-vivo spectroscopy in 60 patients.
      Highest values for specificity and sensitivity of MRI were achieved in the area
      of the skull base and petrous bone. In comparison to other imaging modalities,
      the exact differentiation of pathological alterations such as neurinoma,
      meningioma and glomus tumors succeeded with high accuracy. In the region of the
      naso- and oropharynx, plain MRI revealed in 77% of the cases adequate diagnostic
      information, which could be significantly increased with application of the
      paramagnetic contrast agent Gd-DTPA. Due to multiplanar slice orientation and
      improved soft tissue differentiation MRI proved to be superior to other imaging
      techniques in salivary glands and in the region of the neck. As a conclusion, the
      advantages of MRI are the depiction and visualization of small infiltrations as
      well as the high sensitivity and specificity of this imaging modality.

PMID- 1388474
TI  - [1,000 ear operations--a critical analysis and clinical consequences].
AB  - 1028 ear operations which were performed by our department during the last few
      years are being analysed in the study. 649 of them were carried out to improve
      hearing, 245 to cure the middle ear; 120 were reoperations, and 14 could not be
      classified. The patients were diagnosed as follows: 280 with and 279 with other
      forms of cholesteatoma, 151 with otosclerosis, 20 with deformations, 89 with a
      trauma, and 20 with a tumour of the middle ear. Of these, only reoperations of
      cholesteatoma, chronic otitis media and tympanosclerosis were examined in further
      detail in this research. 54 (of a total of 280) patients diagnosed with
      cholesteatoma were surgically treated a second time. The reason for reoperation
      was recurrent cholesteatoma in 70% of the cases, and a planned second-look
      operation after one year in 30%. In second-look operations, ossicular chain
      reconstruction was performed in most cases, but in another 11%, recurrent
      cholesteatoma was found. The majority of recurrencies occurred either 2 to 4
      years after primary operation or after 11 years. 44 of a total of 297 patients
      with chronic mesotympanic otitis media were re-operated on: 57% of them for
      recurrent inflammation, and 43% for ossicular chain reconstruction as a planned
      second-step operation. The majority of reoperations occurred within the first
      year after primary operation, continually decreasing for up to five years
      afterwards. The following conclusions can be drawn from these results: 1. Often
      the patients suffer from extended cholesteatoma, so that at first curative
      surgery is necessary, while the ossicular chain can be reconstructed by a second
      operation only.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388475
TI  - [Experimental study of airflow in the main nasal cavity of the human using a nose
      model].
AB  - Airflow patterns of nasal cavities in a human nasal fossa model were examined in
      this study. Our 1:1 model of the whole nose (both nasal fossae were moulded)
      gives a good insight into all parts of the nasal cavities. Staining of flow paths
      visualised that the main stream of air flow passes through the inferior nasal
      duct in inspiration and expiration. All regions of the nasal fossa were reached
      by fluid movements and could be marked with staining solution. Under static
      conditions laminar flow without turbulent profiles was seen in all sections of
      the nasal cavities. This technique of detection of flow characteristics in the
      nasal cavities provides a good tool for further research on flow and deposition
      characteristics of aerosols.

PMID- 1388476
TI  - [Significance of immune reactions to cartilage tissue in use of cartilage
      transplants in nose surgery: detection of anti-collagen antibodies].
AB  - In a group of patients who showed repeated resorption or rejection of the
      transplanted cartilage graft, the immune response against a broad spectrum of
      collagen, namely, types I, II, VI, IX and XI, was investigated. We found a
      humoral immune reactivity against collagen type IX und XI, and to a lesser degree
      against collagen type I, demonstrating a specific immune response to these matrix
      collagens. These data suggest that some of the unsuccessful results obtained with
      cartilage grafts may be influenced by factors independent of the operative
      technique, such as immunological reactions.

PMID- 1388477
TI  - [History of instrumental measuring of hearing acuity: the first acumeter].
AB  - The necessity of measuring the acuity of hearing in a reproducible way arose for
      the first time when the invention of Volta's pile in 1800 seemed to present the
      opportunity of curing deafness. For this purpose Chr. H. Wolke in Jever, Northern
      Germany, in 1802 devised two instruments which he called "acumeter". Details of
      these instruments were hardly known, and Wolke's publication was believed to be
      lost. The author has now succeeded in tracing Wolke's publication and another
      associated paper by J. J. A. Sprenger. Hence, the circumstances of Wolke's and
      Sprenger's work and details of these first acumeters are now being published
      together with original figures and the correct dimensions of the instruments. The
      acumeters had a pendulum-like hammer that would strike against a plate swinging
      down from varying heights that could be read in degrees of angle from a scale.
      One of the instruments was made of wood. It was 1.50 m high, with the pendulum
      raised to the maximal position 2.70 m. The other instrument of similar
      construction was made of metal and about half the size of the first one, with a
      height of 0.70 m or 1.30 m respectively. For comparison Itard's acumeter is
      presented which was published in 1821. It worked on the same principle, and it is
      likely that Itard had been inspired by Wolke's paper. The development of
      mechanical acumeters after Wolke's and Itard's instruments is outlined briefly.

PMID- 1388478
TI  - [Toxic drug-induced hyposmia with lovastatin].
AB  - We present the first case of hyposmia after application of lovastatin. Unclear
      disorders of smell should prompt a detailed drug anamnesis.

PMID- 1388479
TI  - [Middle ear ventilation by blowing up a balloon with the nose].

PMID- 1388481
TI  - ATLS and beyond.

PMID- 1388480
TI  - [Impairment of taste perception and extent of patient education in
      tonsillectomy].

PMID- 1388482
TI  - Preparation of statements by medical witnesses: the use of medical evidence in
      criminal prosecutions.

PMID- 1388483
TI  - The effect of the Cornwall and Isles of Scilly helicopter ambulance unit on the
      ambulance services' ability to deliver acutely traumatized patients to hospital.
AB  - OBJECTIVE: to determine whether the use of a helicopter ambulance unit enabled an
      ambulance service to deliver acutely traumatized patients to hospital more
      quickly. DESIGN: retrospectively collected ambulance service and hospital records
      data analysed longitudinally. SETTINGS: The ambulance service and the major
      casualty department in Cornwall. INTERVENTION: the provision of a helicopter
      ambulance unit to a county ambulance service. SUBJECTS: patients with compound
      lower limb fractures carried as emergencies by an ambulance service. Principle
      outcome measure: ambulance 'mission times'. RESULTS: the ambulance services'
      ability to deliver emergency patients to hospital more quickly when the
      helicopter unit was available was not demonstrated. In some instances
      availability of the helicopter unit probably delayed the timely delivery of
      emergency patients to the casualty department. CONCLUSION: until a more effective
      helicopter deployment strategy is in operation it is unlikely that mission time
      savings will occur.

PMID- 1388484
TI  - Role of zinc in post-injury wound healing.

PMID- 1388485
TI  - The Purley train crash mechanism: injuries and prevention.
AB  - On the afternoon of Saturday 4th March 1989 two trains, both bound for London
      Victoria Station, collided. Part of the rear train rolled down a steep railway
      embankment and jack-knifed against a tree. The mechanism of the crash and the
      injuries sustained by the 55 victims who were seen in the A&E Department of the
      Mayday University Hospital are described. Improvements in signalling technology
      and design of rolling stock which may reduce both the risk of collision and
      severity of injury in future accidents are discussed.

PMID- 1388486
TI  - The Purley train crash: procedural difficulties.

PMID- 1388487
TI  - Complaints against doctors in an accident and emergency department: a 10-year
      analysis.
AB  - We carried out an analysis of complaints against doctors in our Accident and
      Emergency Department received from 1 January 1979 to 31 December 1988. There were
      66 complainants in all, comprising 37 relatives, 21 patients and eight persons
      acting in a professional capacity. The majority of complaints (80 out of 125)
      were about poor communication and dissatisfaction with diagnosis and treatment. A
      small number of complainants had unrealistic expectations of the Accident and
      Emergency service. A total of 83.3% of complaints were against Senior House
      Officers who saw 61.3% of all patients. We concluded that an improvement in the
      communicative, diagnostic and therapeutic skills of doctors would minimize
      justified complaints.

PMID- 1388488
TI  - Orbital cellulitis.
AB  - Orbital cellulitis is an emergency. It may cause blindness and progress to life
      threatening sequelae such as brain abscess, meningitis and cavernous sinus
      thrombosis. Successful management is dependent upon urgent referral and immediate
      treatment. Although isolated eyelid erythema and swelling usually indicate
      primary infection anterior to the orbital septum, they may also be the first
      signs of an underlying frontal or ethmoidal sinusitis. The condition always
      requires emergency referral to both an ophthalmologist and otorhinolaryngologist.

PMID- 1388489
TI  - The lateral soft tissue neck X-ray in accident and emergency medicine.
AB  - Five patients with upper aerodigestive tract pathology seen acutely in the
      Accident and Emergency department at St Mary's Hospital, London are presented.
      The value of the lateral soft tissue neck X-ray in their diagnosis is discussed.

PMID- 1388490
TI  - Plasma catecholamine responses in acute severe asthma.
AB  - Twenty patients presenting to an A&E department with acute severe asthma were
      studied. Despite clinically severe airway obstruction few had raised
      catecholamine levels. However several patients with impending respiratory arrest
      had markedly elevated catecholamine levels, and relationships are demonstrated
      between these levels and other measures of disease severity.

PMID- 1388491
TI  - Waiting times and patient satisfaction in the accident and emergency department.
AB  - A survey of the waiting times and patients' opinions of these times was
      undertaken in a busy district general hospital A&E department. The various
      components of the overall waiting time are analysed and specific points of the
      patients' attendance, where waiting times were prolonged, are identified.
      Standards are derived which is hoped may result in 75% of patients being
      satisfied with the duration of their wait. The current levels of achievement are
      compared with these standards. Suggested and actual improvements to the
      department to improve our performance are described.

PMID- 1388493
TI  - Percutaneous ultrasound guided extraction of non-palpable soft tissue foreign
      bodies.
AB  - Ultrasound is being increasingly used in the diagnosis of the soft tissue foreign
      body (FB), in particular for the nonradio-opaque materials which may not be
      visualized with conventional radiography (Fornage & Schernberg 1986). A simple
      technique for ultrasound guided FB extraction under local anaesthesia is
      described, and comment is made upon our preliminary experience and pitfalls.

PMID- 1388492
TI  - Advanced airway control in trauma resuscitation.
AB  - Definitive airway control which may require endotracheal intubation with or
      without an induction agent and muscle relaxant is an essential component of
      trauma resuscitation. We reviewed the delivery of advanced airway care in the
      resuscitation room of a regional trauma centre. This prospective survey suggests
      that in the absence of an experienced anaesthetist, A&E staff with a background
      of suitable training and experience may undertake the anaesthetic responsibility
      associated with securing a definitive airway when the situation demands.

PMID- 1388494
TI  - Occupational accidents presenting to the accident and emergency department.
AB  - A prospective survey of patients attending the major Accident and Emergency
      Department in Aberdeen was undertaken. This department serves a population of
      500,000 and sees some 50% of all accidents in the region. All work-related
      injuries were identified and information relating to the circumstances of the
      accident, injury sustained, and treatment required was sought. Work-related
      injuries accounted for 16.5% of new patients attending the department. The
      commonest injury type was a laceration to a finger. Three hundred and eighty
      diagnostic X-rays were undertaken and a total of 910 treatments were required
      over a 27-day period. On an annual basis, it is estimated that some 5100
      radiographs and 12,300 medical treatments would be required for work-related
      accidents. It is estimated that 30% of injuries to the hands and feet would have
      been prevented by the wearing of appropriate personal protective equipment. The
      majority of workplace accidents were correctly referred to A&E and any efforts to
      reduce this workload must concentrate on preventive measures in the workplace.
      This paper suggests that documenting work-related accidents and determining
      targets for preventive action would reduce the number of attendances at A&E units
      with a potential significant saving for industry and the National Health Service.

PMID- 1388495
TI  - Intracardiac therapy following emergency thoracotomy in the accident and
      emergency department: an experimental model.
AB  - For a select group of patients with penetrating chest trauma, immediate
      thoracotomy in the accident and emergency department offers the only chance of
      survival. Foley catheters have been used to achieve haemostasis in cardiac wounds
      but are not widely used for intracardiac fluid and drug administration during
      resuscitation. In an anatomical model designed to assess this procedure an
      average flow rate of 275 ml min-1 was achieved. The equipment required is readily
      available and easily assembled.

PMID- 1388497
TI  - Flying squad response to out-of-hospital cardiac arrest--a decade of experience.
AB  - The Flying Squad (MEDIC I) based at the Royal Infirmary, Edinburgh, commenced
      operation in 1980. The MEDIC I response to out of hospital non-traumatic cardiac
      arrest over the past decade is reported. On-scene resuscitation was attempted in
      384 patients. A total of 149 (39%) patients were successfully resuscitated and
      transferred to hospital. Thirty-six (9.4%) patients survived to discharge from
      hospital. Patients receiving basic life support prior to the arrival of MEDIC I
      and in ventricular fibrillation had a survival rate of 14.5% (25/174). During
      1988-89, 21 patients were initially attended by ambulance crews equipped with
      semi-automatic external defibrillators and eight (38%) of these patients
      survived. The response of a hospital-based flying squad to support trained
      ambulance crews, especially when equipped with a defibrillator may provide an
      economically and operationally feasible alternative to training all first
      responders in the full range of paramedic skills.

PMID- 1388496
TI  - Prevalence of human immunodeficiency virus risk factors in patients attending an
      accident and emergency department.
AB  - The prevalence of human immunodeficiency virus (HIV) risk factors was evaluated
      by questionnaire survey in 1565 consecutive patients who attended an adult A&E
      department in Brisbane over a 2-month period. The survey revealed that a total of
      144 (9.2%) patients could be considered at risk of HIV infection (high-risk
      group) because of known seropositivity, admission to HIV high-risk factors or
      engaging in high-risk activities. The remaining 1421 patients who did not
      acknowledge any high-risk behaviour were classified as an 'unknown-risk' group.
      More than 70% of the HIV high-risk patient group were under the age of 30 years.
      A total of 275 (17.6%) patients presented with open wounds and/or needed
      hospitalization (23 [1.5%] high-risk patients). Of the 490 respondents who
      engaged in short term sexual relationships, 310 (63.3%) practised unprotected
      coitus, 32 of these including four seropositives were classified in the high-risk
      group. The patients were asked if they were in favour of an HIV testing service
      at their local A&E department; 1324 (86.6%) were in agreement 121 of whom were in
      the high-risk group. There was no significant difference (chi 2 = 0.093: P
      greater than 0.7) in opinion between the 'unknown risk' and high-risk patient
      groups on this matter.

PMID- 1388498
TI  - Management of the moribund carbon monoxide victim.
AB  - Carbon monoxide (CO) poisoning is the commonest single cause of fatal poisoning
      in the U.K. (Broome & Pearson, 1988). The clinical features are numerous and
      include headache, fatigue, dizziness, confusion, memory loss, paraesthesia, chest
      pain, abdominal pain, nausea, and diarrhoea as well as coma, convulsions and
      death. Without adequate treatment many patients develop neuropsychiatric sequelae
      including headaches, irritability, memory loss, confusion and personality
      changes. The diagnosis of CO poisoning is often suggested only by circumstances
      surrounding the victim, and remains a challenge to the A&E department. Hyperbaric
      oxygen therapy (HBO) is internationally accepted as the most powerful form of
      treatment in severe cases (Drug & Therapeutics Bulletin, 1988; Lowe-Ponsford &
      Henry, 1989). However, in the U.K. treatment with HBO is often not considered due
      to lack of hyperbaric facilities (Meredith & Vale, 1988; Anand et al., 1988), and
      due to inadequate awareness on the part of hospital staff. We report a case of a
      patient deeply unconscious as a result of CO poisoning, in which serial
      treatments with HBO over a period of 14 days, produced dramatic results.

PMID- 1388500
TI  - Exposure of the hands to ionizing radiation in the resuscitation room of an
      accident & emergency department.
AB  - Exposure of the hands to ionizing radiation in the resuscitation room of an A&E
      department was measured in eight health care personnel over 3 consecutive months.
      The radiation levels did not exceed those limits currently recommended by the
      International Commission on Radiological Protection 1990. The level recorded in
      one individual did exceed the level set at the Lothian Health Boards
      investigation limit. In only five of 85 occasions were lead gloves worn by the
      doctor during cross table lateral cervical radiographs. Recommendations are made
      for reducing the radiation exposure to the hands.

PMID- 1388499
TI  - Toxicity awareness and unintended suicide in drug overdoses.
AB  - The objective of this paper is to determine patients awareness of the toxicity of
      the drugs they overdose with, the source of these drugs, and whether they would
      have taken them had they been fully aware of their toxicity, and to examine the
      implications for prevention. A prospective review of one hundred consecutive
      overdoses admitted through an A&E department was carried out. Awareness was
      scored by a ranking questionnaire and intent by response to a standard question
      when toxicity was explained. Paracetamol was most the most frequently taken drug
      (39 cases). Overall awareness of toxicity was low. Twenty-eight patients (30%)
      said they would not have overdosed if they had been aware of the toxicity of what
      they had taken. Forty-nine per cent of patients took someone elses tablets. There
      is a rise in analgesic poisoning from 1976. Higher toxicity awareness may reduce
      the incidence of drug overdose. Smaller prescriptions and over the counter
      preparations especially paracetamol and limited access to toxic drugs, especially
      in high-risk homes, should reduce both the number and severity of overdoses. It
      is possible that a number of deaths from deliberate drug overdose may be
      unintentional as 30% of survivors in this study did not intend the toxic effects
      of the drug taken.

PMID- 1388501
TI  - Public awareness of home accident risks--some implications for health promotion.
AB  - Through daily contact with injured people there was a feeling that most people
      are sufficiently aware of the dangers in specific risk factor activities, but
      were not fully aware that they could do a lot to prevent harm coming upon
      themselves. This paper describes the results of a self-administered questionnaire
      about the accidents people suffered at home, their level of awareness of the risk
      they were undertaking, whether they had had a similar accident before, what they
      think the recovery period from their injury is likely to be and knowledge of, and
      accidents involving, 17 generally known risk activities. The results confirm that
      most people are indeed aware of dangers yet a large number still have accidents
      in spite of that. The results also indicate that campaigns advising people how to
      avoid these dangers could be successful.

PMID- 1388502
TI  - Irregular discharge against medical advice from the accident and emergency
      department--a cause for concern.
AB  - An irregular discharge (ID) from the A&E department is an undesirable, but
      relatively common occurrence. A prospective study was undertaken to quantify the
      size of the problem and by arranging a subsequent review of the patient, to
      determine the clinical outcome. Over a 3-month period, 139 patients (0.73%) of
      attendances) took their own discharge against medical advice. A further 566
      patients (3.03% of attendances) left prematurely prior to any medical assessment
      (DNW). Attenders irregularly discharged, often with serious untreated conditions.
      A high proportion were intoxicated with alcohol (65.5%). Attempted follow up
      proved difficult and incomplete. Patients with serious conditions appeared to
      return spontaneously for further care. Methods of minimizing the numbers of
      patients who take an ID or DNW are discussed. Taken together, the numbers of
      these attenders leaving prematurely, can be used as a valid performance indicator
      of the delivery of health care in the A/E department.

PMID- 1388503
TI  - Cases of assault attending a childrens accident and emergency department: an
      epidemiological study.

PMID- 1388504
TI  - Intra-articular dislocation of the patella.

PMID- 1388505
TI  - The Flexipore 6000 membrane as a wound dressing for use in the accident and
      emergency department.

PMID- 1388506
TI  - Thrombolytic therapy in A&E departments in the U.K.

PMID- 1388507
TI  - Spontaneous pneumomediastinum.

PMID- 1388508
TI  - Paramedic care.

PMID- 1388509
TI  - Seat-belt injury.

PMID- 1388510
TI  - Rare diseases do occur: an acute presentation of Huntington's chorea.

PMID- 1388511
TI  - Stick stuck in stoic.

PMID- 1388512
TI  - Management of corneal foreign bodies in A&E departments.

PMID- 1388513
TI  - Trauma courses for senior house officers.

PMID- 1388514
TI  - [Pyoverdins from Pseudomonas putida].
AB  - The structures of two pyoverdins (Pp1 and Pp2) and one dihydropyoverdin (dihydro
      Pp2) from a strain of Pseudomonas putida have been elucidated by spectroscopic
      methods and degradation studies. The pyoverdins Pp1 and Pp2 consist of a
      chromophore which was identified as (1S)-5-amino-2,3-dihydro-8,9-dihydroxy-1 H
      pyrimido[1,2-a]quinoline-1- carboxylic acid substituted at the amino group with a
      3-carboxypropanoyl or a succinamoyl residue and at the carboxy group with the N
      terminus of L-Ser-L-Thr-D-Ser-L-Orn-L-threo-(OH)Asp-[D-Glu + L-Dab]*-L-Ser-D-allo
      Thr- L-c(OH)Orn. Dihydro-Pp2 differs from Pp2 only in the chromophore, which is
      saturated at carbons 5 and 6. All compounds contain a tetrahydropyrimidine moiety
      ([D-Gln + L-Dab]*) resulting from the condensation of 2,4-diaminobutyric acid and
      glutamine.

PMID- 1388515
TI  - Degradation of pentachlorophenol by Mycena avenacea TA 8480--identification of
      initial dechlorinated metabolites.
AB  - Cultures of the basidiomycete Mycena avenacea TA 8480 were shown to metabolize
      pentachlorophenol (PCP), 2,3,5,6-tetrachloro-p-hydroquinone (TeCHQ), and 2,3,5,6
      tetrachloro-p-benzoquinone (TeCBQ). The first metabolite of the PCP degradation
      pathway was identified as TeCBQ which in a second reaction is reduced to the
      hydroquinone TeCHQ. Subsequently dechlorination of TeCHQ yielded 3,5,6-trichloro
      2-hydroxy-p-benzoquinone (TCOHBQ). The specific degradation rate for PCP was 1.4
      mg x g dry mycelia -1 x day-1. The initial dechlorination rate of TeCHQ was 5.9
      mg x g dry mycelia-1 x hour-1. None of the compounds supported growth of the
      fungus.

PMID- 1388517
TI  - The effect of resorcinolic lipids on phospholipid hydrolysis by phospholipase A2.
AB  - The effects of resorcinolic lipids (5-n-alk(en)ylresorcinols) isolated from
      cereal grains on the phospholipase A2 catalyzed hydrolysis of phospholipid
      vesicles were examined. Studied compounds inhibited the apparent enzyme activity
      at the molar fraction in the membrane as low as 0.025, which is equivalent to the
      concentration of 3 microM. This effect was visualized by dramatic increase (over
      ten-fold) of the latency period of the reaction progress. This makes resorcinolic
      lipids one of the most potent inhibitors of phospholipase A2 among already
      studied compounds. Highest inhibitory activities were shown for dienoic and
      monoenoic homologs of 17 carbon atoms in the aliphatic chain. Both saturation of
      the chain and the increase of its length reduced inhibitory properties of
      resorcinolic lipids. The data suggest that the compounds studied in this paper
      like other known amphiphilic inhibitors of phospholipase A2 owe most of their
      effects to the ability to modify the quality of the substrate interface. These
      are the alteration of the enzyme binding, velocity of the formation and
      redistribution of the products. However part of the effect seems to be attributed
      to direct interaction and modification of enzyme properties by
      alk(en)ylresorcinols.

PMID- 1388516
TI  - X-ray studies on phospholipid bilayers. XII. Interactions of pentachlorophenol
      with myelin.
AB  - Pentachlorophenol (PCP) is a widely used pesticide, particularly for the
      preservation of wood. Given its high toxicity and resistance to degradation it
      has become a dangerous environmental pollulant. Due to its high lipophilicity,
      PCP is able to partition into the lipid bilayer of cell membranes disrupting
      several vital functions. The present research was concerned with the effects that
      the chronic administration of PCP could produce in vivo to the sciatic nerve of
      rats. X-ray diffraction patterns obtained from freshly dissected and dried
      sciatic nerves of PCP treated rats did not show significant differences in their
      reflections with respect to those present in the patterns from untreated animals.
      However, morphological studies performed by optical and electron microscopy
      showed degenerative changes in about 10% of the A and B type of nerve fibers.

PMID- 1388518
TI  - Amines in the marking fluid and anal sac secretion of the tiger, Panthera tigris.
AB  - Analysis of the marking fluid of two tigers (one Bengal and one Sumatran) by GC
      using an amine-specific column and a nitrogen-specific detector has shown the
      presence of the following amines: ammonia, methylamine, dimethylamine,
      trimethylamine, triethylamine, propylamine, and butane-1,4-diamine (putrescine).
      In contrast to previously published reports, we were unable to detect 2
      phenylethylamine. The anal sac secretion was found to have a similar amine
      content.

PMID- 1388519
TI  - Resonance effect of microwaves on the genome conformational state of E. coli
      cells.
AB  - The effect of low intensity microwaves on the conformational state of the genome
      of X-irradiated E. coli cells was studied by the method of viscosity anomalous
      time dependencies. It has been established that within the ranges of 51.62-51.84
      GHz and 41.25-41.50 GHz the frequency dependence of the observed effect has a
      resonance nature with a resonance half-width of the order of 100 MHz. The power
      dependence of the microwave effect within the range of 0.1-200 microW/cm2 has
      shown that a power density of 1 microW/cm2 is sufficient to suppress radiation
      induced repair of the genome conformational state. The effect of microwave
      suppression of repair is well reproduced and does not depend on the sequence of
      cell exposure to X-rays and microwave radiation in the millimeter band. The
      results obtained indicate the role of the cell genome in the resonant interaction
      of cells with low intensity millimeter waves.

PMID- 1388520
TI  - Dynamics and kinetics of enzymes. Kinetic equilibrium of forces in biochemistry.
AB  - To explain the high specificity, high reaction rate, and high thermodynamic
      efficiency in enzymatic processes, cooperation of the enzyme with a molecular
      transfer unit is assumed. A "kinetic equilibrium of forces" is suggested, which
      enables high reaction rates to occur under equilibrium conditions and a thorough
      examination of the substrate to be made without consumption of free energy. In
      case of ATPases, ion-binding proteins are the most probable transfer units. By
      analyzing the elementary effect in muscle contraction it is shown that the new
      theorem may be of substantial value in elucidating biochemical processes.

PMID- 1388521
TI  - Enhancing the training of internal medicine residents at Stanford by establishing
      a model group practice and raising its clinical educators' status.
AB  - The education of residents is shifting to the ambulatory care setting. In
      addition, there is a growing trend toward managed care and increasing competition
      for patients to be served by "real-world" practices. The authors describe the
      formation and operation of a program that was established in 1981 at the Stanford
      University School of Medicine to respond to these changes: the Stanford Medical
      Group (SMG), a model group practice in internal medicine that operates within the
      academic medical center. Because raising the status of the clinician-educator
      faculty was a critical issue for the SMG, the authors also describe the Medical
      Center Professoriate, a separate faculty track created in 1989 to recognize and
      reward Stanford's clinician-educators. The authors conclude that the SMG has
      succeeded in its training and patient care goals and has weathered the great
      changes in the health care environment that have taken place since 1981. They
      also report that the separate faculty track is serving its purpose well. They
      hope that educators and program directors at other academic medical centers may
      find the descriptions of the SMG and the professoriate useful in solving similar
      problems.

PMID- 1388522
TI  - How attending physicians make instructional decisions when conducting teaching
      rounds.
AB  - When attending physicians are conducting teaching rounds, they rapidly decide
      what and how much to teach in response to each case presentation. How do they
      make these instructional decisions? The author performed a qualitative study of
      the instructional reasoning and actions of six distinguished clinical teachers in
      general internal medicine to address this question. Four data sources were used:
      interviews with teachers and learners, a structured task, transcripts of teaching
      rounds, and week-long observations of each ward team. The teachers in this study
      engaged in substantial amounts of planning before rounds and reflected on rounds
      afterwards. When listening to a case presentation during rounds, they quickly
      diagnosed the patient's problems and simultaneously diagnosed their learners'
      levels of understanding. These diagnostic assessments were used to tailor content
      specific curriculum scripts for instruction. Throughout the rounds, the teachers
      also engaged in interactive thinking, decision making, and improvisation. The
      author's findings allowed him to hypothesize a model of clinical instructional
      reasoning and action; they contribute new insights into the interplay between
      reasoning in a discipline and pedagogical reasoning. Instructional reasoning and
      clinical reasoning were found to be closely linked through the use of scripts.
      The implications of these and other findings for medical faculty development are
      discussed.

PMID- 1388524
TI  - Ubiquitous computing.

PMID- 1388523
TI  - An interdisciplinary clerkship model for teaching primary care.

PMID- 1388525
TI  - Developing a computer literacy curriculum for residents.

PMID- 1388526
TI  - The NIH Strategic Plan.

PMID- 1388527
TI  - The choice for research policy: more or better?

PMID- 1388528
TI  - Criticisms of a report on teaching with interactive videodiscs.

PMID- 1388529
TI  - Must psychiatry education be a failing endeavor?

PMID- 1388530
TI  - The need to train residents to write effectively.

PMID- 1388531
TI  - Specialty selection and success in obtaining choice of residency training among
      1987 U.S. medical graduates by race-ethnicity and gender.
AB  - The authors developed baseline data on specialty selection and success in
      obtaining residency positions for the medical school graduates of 1987 who
      participated in the National Resident Matching Program (NRMP), compared by gender
      and race-ethnicity. They focused on primary care specialties and obstetrics
      gynecology versus all other specialties, and sought to identify group differences
      in (1) patterns of specialty preference, (2) evolution of specialty choice from
      before to after medical school, (3) success in attaining the first choice of
      specialty through the NRMP, and (4) patterns in switching from an alternate
      specialty (ranked second or lower) to the first-choice specialty between the
      first and second years of residency training. The results showed substantial
      intergroup and intragroup variations, both before and after medical school, for
      family practice, internal medicine, and obstetrics-gynecology. Examination of
      NRMP outcomes revealed that the underrepresented-minority (URM) graduates,
      particularly men, were less successful both in achieving any match and in
      matching to their first-choice specialties. Analyses of patterns in switching
      specialties revealed several important facts about those who were matched to
      alternate specialties: (1) over half entered their first-choice specialties in
      the second year; (2) women had more success in switching to their first-choice
      specialties than did men, particularly among the URMs; (3) among those who
      received alternate specialties, the URM women were more likely than the URM men
      to leave graduate medical education by the second year (reversing the trend for
      the other groups); and (4) individuals whose alternate specialties were in
      primary care were much less likely to switch to their first-choice specialties.

PMID- 1388532
TI  - Self-assessment programs and their implications for health professions training.
AB  - Although expected of all health professionals, self-assessment skills are seldom
      addressed directly in training. A previous review by the author identified
      curricular criteria associated with improved accuracy and validity in self
      assessments of knowledge and performance in curriculum studies published between
      January 1970 and February 1990. The present review analyzed 11 studies that meet
      those criteria. Eight studies were of implementations of self-assessment
      components within training programs in the health professions, and three involved
      other training environments. Most described initial disorientation or opposition
      on the part of learners, attributed to unfamiliar roles and to learners'
      distrust. The curricula that successfully negotiated the transition to self
      assessment norms reported noncognitive benefits such as improvements in morale,
      motivation, and communications among learners and faculty. Reported cognitive
      benefits included improvements in knowledge, performance, and self-analysis of
      performance. The constellation of effects suggests that effective self-assessment
      programs may promote more mature, collegial, and productive learning
      environments, particularly suited to the training of health professionals. Most
      curricula fostering effective self-assessment did not require extraordinary
      resources, and none jeopardized traditional standards. No evidence was found to
      support or challenge the expectation that self-assessment training would transfer
      to later work settings.

PMID- 1388533
TI  - Declining class size and the decline in graduates choosing family medicine.
AB  - In light of the major concern about the marked decline in the numbers of
      graduates from U.S. medical schools who are entering family medicine, the authors
      analyzed the effect of declining class size on the numbers of graduates entering
      family medicine residencies. Data were analyzed from ten years of graduating
      classes (1981-1990) from the 81 medical schools graduating the most family
      physicians. The analysis confirmed that declining class size is related to the
      decline in the production of family physicians. In particular, the 31 schools
      with the largest declines in the numbers of graduates overall (from the early
      1980s compared with the late 1980s and 1990) demonstrated as a group a large fall
      (nearly 25%) in the production of family physicians. The authors conclude that
      the large reductions in class size in many medical schools are associated with
      even larger reductions in the numbers of future family physicians being graduated
      from U.S. medical schools.

PMID- 1388534
TI  - Rural training tracks in four family practice residencies.
AB  - The use of rural training tracks (RTTs) in family practice residencies is a new
      strategy (beginning in the late 1980s) to increase the number of residents
      selecting rural careers. The authors describe the four residencies (in
      Washington, Nebraska, New York, and Kentucky) that have established RTTs. The
      first residency year is completed in an urban tertiary care center, and the
      second and third years are completed in a distant rural community wherein the
      primary faculty are the members of a rural family practice group. Inpatient
      experience for the residents is provided by community hospitals that offer
      obstetrics, emergency room care, and first-line critical care. The residents'
      training is supplemented by specialty faculty practicing in the rural
      communities. The curricula are highly structured and are evaluated to ensure
      training experiences of high quality. The RTTs' financial support comes from
      state initiatives, hospital reimbursement, recruitment budgets, and outpatient
      care revenues. The authors conclude that the RTT concept has the potential to
      lessen the shortage of rural physicians.

PMID- 1388535
TI  - A national model of faculty development in addiction medicine.
AB  - Increasing the number of faculty with expertise in addiction medicine is one of
      the challenges facing the medical community in the 1990s. To meet this challenge,
      the Society of Teachers of Family Medicine created a faculty development course
      to increase the expertise of family practice faculty involved in teaching
      residents. The authors describe the development, implementation, and consequences
      of the five-day intensive course that was taught to 165 participants at ten sites
      in 1990. The participants' self-reporting before and three months after the
      course showed significant increases in the numbers of participants who taught
      addiction medicine in eight of 11 clinical situations. The authors conclude that
      the course represents a model of faculty development in addiction medicine that
      is applicable to other specialties and health professions.

PMID- 1388537
TI  - Geriatrics fellows' perceptions of the quality of their research training.
AB  - In the last quarter of 1987-88, 95 second- and third-year geriatrics fellows were
      surveyed to examine their perceptions of the quality of research training
      available through their programs. A three-phase Delphi survey method was used,
      with the numbers of individuals responding per phase ranging from 58 (61%) to 68
      (72%). The responses were clustered in five areas by means of factor analysis
      using a varimax rotation procedure. The fellows perceived their research training
      to be inadequate, primarily due to insufficient time for research activities and
      to inadequate exposure to research-qualified scientists. The authors conclude
      that although the fellows strongly supported the notion of a research-focused
      third fellowship year, implementing such a plan may be futile if new resources
      are not made available.

PMID- 1388536
TI  - Developing students' cognitive skills in a problem-based surgery clerkship.
AB  - In 1989-90, 57 students in a new program for the third-year surgery clerkship at
      the University of Kentucky College of Medicine participated either in a control
      group (22 students) receiving a traditional method of instruction (Socratic
      instruction, SI) or in an experimental group (35 students) taking part in problem
      based learning (PBL) sessions. The two groups' performances on six evaluative
      instruments designed to test either their factual knowledge or their knowledge
      application (i.e., clinical problem-solving skills) were compared. The measures
      of factual knowledge were associated with higher scores for the SI group on two
      quizzes; scores were not significantly different on another quiz and on a
      cumulative final examination. The measures of knowledge application (administered
      at the end of the clerkship) were associated with higher scores for the PBL
      group: scores were significantly higher on a modified essay examination and
      approached significance on a standardized-patient examination. The authors
      conclude that their results (1) have important similarities to those of previous
      research suggesting that a PBL format is essentially equivalent to a traditional
      curricular format in improving students' factual knowledge and (2) support the
      hypothesis that PBL is superior in improving clinical problem-solving skills.

PMID- 1388538
TI  - Relationship between indebtedness and the specialty choices of graduating medical
      students.

PMID- 1388539
TI  - Improving the educational process of cancer case conferences.

PMID- 1388540
TI  - A survey of study methods, preparation time, test-taking strategies, and
      perceptions of test validity on a clinical performance-based examination.

PMID- 1388541
TI  - Relationship between scores on NBME basic science subject tests and the first
      administration of the newly designed NBME Part I examination.

PMID- 1388542
TI  - Results of the initial administrations of the NBME comprehensive Part I and Part
      II examinations.

PMID- 1388543
TI  - Assessing practicing physicians in two settings using standardized patients.

PMID- 1388544
TI  - First-visit bias in the measurement of clinical competence with standardized
      patients.

PMID- 1388545
TI  - Influence of premedical preparation in the humanities and social sciences on
      attitudes toward patient care: a study of Quebec medical students and recent
      graduates.

PMID- 1388546
TI  - Prediction of medical students' academic performances: does the admission
      interview help?

PMID- 1388547
TI  - The influence of a patient's age on problem-based tutorial discussion.

PMID- 1388548
TI  - Do medical students' responses to patients' concerns about AIDS vary based on the
      patient's risk and the gender of student?

PMID- 1388549
TI  - A large-scale multicenter objective structured clinical examination for
      licensure.

PMID- 1388550
TI  - Help! Is anyone listening? An assessment of learning needs of practicing
      physicians.
AB  - We used a theoretical framework of adult learning, physician learning and change,
      and educational evaluation to assess physician--learner needs. The study
      emphasized the physician's perspective and the context of expressed needs. The
      respondents acknowledged ineffective learning patterns and lack of ongoing self
      assessment, and identified changing and specific, emerging, learning needs. New
      roles are suggested for CME providers. We believe our findings support the
      usefulness of an integrated theoretical perspective to guide needs assessment
      that will be cognizant of the complexity of ongoing professional learning.

PMID- 1388551
TI  - Testing the equivalence of multiple-station tests of clinical competence.

PMID- 1388552
TI  - The medical school curriculum--how well do our graduates say we are doing?

PMID- 1388553
TI  - A model for teaching medical students in an ambulatory surgery setting.

PMID- 1388555
TI  - Students' use of prior problem representations when performing computer-based
      simulations: an artificial neural network perspective.

PMID- 1388554
TI  - Improving the care of adolescents: an innovative curriculum for pediatrics
      residents.

PMID- 1388556
TI  - Domain knowledge and information retrieval in bacteriology: an information
      science perspective.

PMID- 1388557
TI  - The use of a patient note to evaluate clinical skills of first-year residents who
      are graduates of foreign medical schools.

PMID- 1388558
TI  - Predictive validity of a required multidisciplinary standardized-patient
      examination.

PMID- 1388559
TI  - The computerization of clinical science examinations and its effect on the
      performances of third-year medical students.

PMID- 1388560
TI  - Effects of supplemental instruction in selected medical school science courses.

PMID- 1388561
TI  - Test security in standardized-patient examinations: analysis with scores on
      working diagnosis and final diagnosis.

PMID- 1388562
TI  - Identifying poor preclinical performers who do well in clerkships.

PMID- 1388563
TI  - Expertise in visual diagnosis: a review of the literature.

PMID- 1388564
TI  - Recent research on university learning and teaching: implications for practice
      and future research.

PMID- 1388565
TI  - The HOME microscope workstation. A new tool for cervical cancer screening.
AB  - The Highly Optimized Microscope Environment (HOME) is a computerized microscope
      design for assisting pathologists and cytotechnologists in routine clinical
      tasks. The prototype system consists of an IBM PC-compatible computer and a light
      microscope in which a built-in high-resolution computer display image is super
      imposed on the optical image of the specimen. Also, an encoding stage and
      objective turret encoder are used to provide continuous monitoring of the stage
      coordinates and microscope magnification to the computer. This allows any
      position on the stage to be uniquely defined. Software, written in C language and
      running under the MS-DOS/MS-Windows environment, is controlled by means of a
      mouse-driven cursor. A specific application has been developed for cervical
      cancer screening, taking into account the needs and constraints of microscopists
      performing this task. Informatics tools offered by the HOME system provide them
      with precise flagging and relocation of objects on the slide, control of the
      scanning pathway, and ability to write and print the report directly through the
      microscope. The computer files generated by microscopic examination are stored
      and contain information available for quality control assessment and laboratory
      management.

PMID- 1388566
TI  - Nuclear protein content and Ki-67 immunoreactivity in nonneoplastic and
      neoplastic thyroid cells.
AB  - The nuclear DNA content in thyroid tumor cells has been shown to be closely
      related to the malignant potential of the neoplasm. Besides DNA, nuclear protein
      (NP) constitutes the major mass of the nucleus. The NP content may vary
      significantly in relation to the proliferative stage in growing as compared to
      growth-arrested cells. The increase in NP content associated with the transition
      from G0 to G1 occurs before the onset of DNA synthesis and may be used to assess
      growth activity. The nuclear DNA and NP contents were analyzed in 90
      nonneoplastic lesions and 75 benign and 62 malignant thyroid tumors. All
      nonneoplastic specimens were euploid, and 1 of 90 was growth activated. In the
      group of benign tumors, 59 were euploid, and 16 were aneuploid. Among these there
      were 5 (9%) of 59 and 6 (38%) of 16 growth-activated specimens, respectively. In
      the group of malignant tumors 57 of 62 were classified as euploid, and in this
      group 12 (21%) showed growth activity according to the NP content. Five of 62
      were aneuploid, and 3 (60%) of these 5 tumors were growth activated. Evaluation
      of the growth activity by means of monoclonal antibody Ki-67 was performed on a
      subgroup of 32 thyroid specimens, both nonneoplastic and neoplastic lesions. Ki
      67 immunoreactivity was observed in 0-1.1% cells of 6 nonneoplastic lesions, in 0
      3.1% cells of 14 benign cells and in 0.2-3.9% cells of 12 malignant thyroid
      tumors. Growth activity, as reflected by the NP/DNA ratio and Ki-67
      immunoreactivity, appears to be low both in nonneoplastic thyroid lesions and
      thyroid tumors.

PMID- 1388567
TI  - Comparison of cell proliferation in breast carcinoma using image analysis (Ki-67)
      and flow cytometric systems.
AB  - Cellular proliferation has been implicated as an important predictor of biologic
      behavior in breast cancer. Cellular proliferation of 95 breast carcinomas was
      evaluated by comparing Ki-67 immunoreactivity in frozen sections quantitated by
      image analysis with S-phase and S + G2/M phase fraction determined by flow
      cytometry on nuclei extracted from fixed, paraffin-embedded sections (modified
      Hedley's technique). These parameters were correlated with traditional
      morphologic features of histologic grade, including mitotic count. Ki-67
      immunoreactivity correlated with S-phase fraction determined by flow cytometry (r
      = .41, P = .001) and with S + G2/M phase fraction determined by flow cytometry (r
      = .29, P = .008). There was also a correlation between histologic grade and Ki-67
      immunoreactivity (r = .30, P = .004) and between histologic grade and S-phase
      fraction (r = .42, P = .0001). Mitotic count correlated with Ki-67
      immunoreactivity (r = .25, P = .015) and with S-phase fraction (r = .35, P =
      .001). Image and flow cytometric analysis systems provide comparable measurements
      of cellular proliferation; their measurements correlate with histologic grade and
      mitotic count in breast cancer.

PMID- 1388568
TI  - Nucleolar organizer region-associated proteins in cancer cells. Quantitative
      investigations on gliomas, meningiomas, urinary bladder carcinomas and pleural
      lesions.
AB  - Using a modified silver staining technique, we investigated nucleolar organizer
      region-associated proteins (AgNORs) in paraffin sections of 156 neoplastic
      tissues and other lesions, including gliomas (n = 41), meningiomas (n = 20),
      urinary bladder carcinomas (n = 58), and neoplastic and reactive lesions of the
      mesothelium of the pleural cavity (n = 37). We found significant differences in
      the mean number and area of AgNORs per nucleus between nonanaplastic and
      anaplastic astrocytomas. In meningiomas AgNOR analysis may be useful to
      distinguish between mostly benign tumors (grade 1 tumors) and atypical ones.
      Urinary bladder carcinomas exhibited a statistically significant increase in both
      AgNOR number and area as the grade of malignancy increased. Diagnostically useful
      differences in the AgNOR configuration between inflammatory and neoplastic
      processes were found for mesothelial lesions. In general, a higher grade of
      malignancy correlated with an increase in the AgNOR number. This was accompanied
      by an increase in the total AgNOR area per nucleus, irrespective of whether the
      size of the individual AgNORs had changed.

PMID- 1388569
TI  - Morphometry and discriminant analysis of the endometrium.
AB  - The authors dated 100 normal endometrial biopsies. Only endometrial specimens
      with histologically confirmed subphases and no evidence of organic disease were
      accepted for study. The morphometry and stereologic measures of the glands,
      lumina and endometrial epithelium were assessed. Quantitative assessment of the
      normal endometrium supported the histologic events that occur in the endometrial
      cycle (proliferative and secretory phases). There was a progressive increase in
      morphometric and stereologic values of the glands, epithelium and lumina during
      the endometrial cycle. Using stepwise discriminant analysis, 94% of the specimens
      were correctly classified into the categories of proliferative and secretory
      phase; two quantitative parameters were required, the epithelial volume density
      and longest luminal diameter. When three subphases within proliferative and
      secretory endometrium were considered, the overall accuracy was 90% and 78%,
      respectively.

PMID- 1388571
TI  - Morphologic scales and relative distances between lesions identified on
      Papanicolaou smears.
AB  - We fit a Gaussian-type curve to a nonmonotonic transform of initial arbitrarily
      given scales (pseudoscalar transform) of a two-way discrete classification table
      by maximizing the likelihood (entropy) and computing morphologic scales of
      clusters of objects identified by visual judgments. The scales give the relative
      distance between pairs of categories or states. Morphologic scales of histologic
      lesions (states) identified on Papanicolaou smears were computed from a confusion
      matrix consisting of 3,545 matched pairs of observations on Papanicolaou smears
      and colposcopically directed biopsies available from the Gynecologic Cytology
      Laboratory, University of Minnesota, between 1985 and 1987. The original
      (uncollapsed) confusion matrix consisted of eight cytologic categories and
      histologic states: normal plus atypical benign, reactive atypia (including
      condylomatous changes); mild, moderate and severe dysplasia; squamous carcinoma
      in situ; invasive squamous cell carcinoma; and other malignancies. The
      morphologic scales are expressed numerically, which reflects a degree of
      confusion between two diagnostic categories or states. Except for malignancies
      other than squamous cell carcinoma, morphologic scales of histologic states seen
      from cytology retained the order of clinical severity. We detected a high degree
      of confusion between severe dysplasia and carcinoma in situ. Malignancies other
      than squamous cell carcinoma fell between moderate and severe dysplasia. Such a
      transposition of the scales in this group containing adenocarcinoma was likely
      due to frequent association of adenocarcinoma with cervical intraepithelial
      neoplasia. Morphologic scales of cytologic categories seen from histology showed
      high degrees of confusion and transpositions between mild and moderate dysplasia
      and between severe dysplasia and carcinoma in situ.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1388570
TI  - Measurement of subvisual changes in cervical squamous metaplastic cells for
      detecting abnormality.
AB  - Quantitative measures of visually normal squamous metaplastic cells exfoliated
      from the uterine cervix were obtained to test the hypothesis that these cells,
      like intermediate squamous and endocervical columnar cells, show subvisual
      evidence of atypia in cases of bonafide squamous intraepithelial neoplasia. The
      cells identified as squamous metaplastic were obtained from 14 abnormal
      (dysplastic) and 9 diagnostically negative cases. Although the cell populations
      so grouped showed no statistically significant differences in overall cell size,
      nuclear area or nuclear/cytoplasmic ratios, there were significant differences in
      nuclear and cytoplasmic densitometric features and in nuclear texture features. A
      combination of three features (nuclear density, texture and cytoplasmic density)
      permitted 76% of the cells to be categorized correctly as originating in normal
      versus abnormal slides. It is concluded that selected quantitative features of
      exfoliated metaplastic cell populations may contribute to improved diagnostic
      accuracy in automated screening for cervical abnormalities.

PMID- 1388572
TI  - Prediction of recurrence in giant cell bone tumors by DNA cytometry.
AB  - The most interesting therapeutic aspect of giant cell bone tumors is which
      patients can be cured without a risk of recurrence by intralesional surgery
      (curettage). To find out the suitability of some DNA cytometric and morphometric
      parameters for showing differences between this group of patients (n = 9) and
      those with recurrence (n = 12), the parameters mean ploidy, 2cDI (mean square
      deviation of the tumor cell DNA content from the normal 2c value), mean nuclear
      area and its variability were calculated from cytologic specimens prepared by a
      cell separation technique from formalin-fixed, paraffin-embedded tissues,
      measuring the values of 100 stromal cells per case by a TV image analysis system.
      Further measurements were performed on 19 cases of different diseases of the bone
      and on an additional 17 cases of giant cell tumors without follow-up. The 2cDI
      allowed us to distinguish the two groups of patients, with and without
      recurrence, without overlap; even the lowest value for patients with recurrence
      was higher than the highest value for cured ones. Mean ploidy analysis resulted
      in a less convincing discrimination of the patients. Mean nuclear area and its
      variability failed to predict recurrence. Single-cell DNA cytometry provided a
      parameter, 2cDI, that was able to predict recurrence in patients with giant cell
      bone tumors with high sensitivity.

PMID- 1388573
TI  - The Hough transform for locating cell nuclei.
AB  - A method of cytologic image segmentation that works purely on the basis of
      geometric information is described. Cell nuclei are assumed to be circular or
      elliptical. The latest ellipse-finding Hough transform is then used to locate the
      nuclei. The results are encouraging.

PMID- 1388574
TI  - Nuclear planimetry and DNA flow cytometry of verruga peruana.
AB  - Verruga peruana is a vascular hyperplasia that is sometimes histologically
      mistaken for a malignant neoplasm. An infiltrative pattern with nuclear
      pleomorphism and mitoses is prominent in some lesions. From a series of lesions
      of verruga peruana, we selected five atypical lesions, two of them closely
      resembling epithelioid angiosarcoma. We used histologic criteria as well as
      morphometry and flow cytometry to further characterize the atypical features of
      the lesions. Histology and morphometry evidenced marked nuclear pleomorphism.
      Flow cytometry failed to reveal aneuploidy and disclosed about 10% of the cells
      to be in the S, G2 and M phase.

PMID- 1388575
TI  - Wind-induced accidents of road vehicles.
AB  - This paper describes the results of a project that collected and collated data
      for wind-induced vehicle accidents that occurred in the United Kingdom during the
      major storm of 25 January 1990. The results of this data analysis are used to
      determine which vehicles are most at risk during windy periods, the nature of the
      accidents that were caused, and the likely values of accident wind speeds. Also
      the adequacy of a computer program that can predict such wind speeds (the program
      BLOWOVER) is assessed as far as the available data allows.

PMID- 1388576
TI  - The effects of compliance cost and specific consequence information on the use of
      safety equipment.
AB  - The effects of compliance cost and warning content on the use of protective
      eyewear by racquetball players were evaluated. Four-hundred-twenty subjects were
      observed for use of eye protection in a field setting. Results indicate that
      proximal placement of eyewear and the inclusion of specific consequence warning
      information increased safety equipment use. Implications of this research for
      augmenting warning effectiveness and safety are discussed.

PMID- 1388577
TI  - A modeling perspective on the culture of driving.
AB  - Each driver is influenced by the collective behavior of other drivers. At the
      same time, each driver is also part of this collective, and thus influences
      others. Underlying many driver control and traffic safety programs are two
      implicit and related assumptions: that drivers are sensitive to the "culture of
      driving" around them and emulate it; and, that a small shift in the behavior of
      few might be amplified or snowball to a much larger effect resulting in a changed
      traffic environment or a modified culture of driving. The paper discusses
      possible mechanisms for the interactions between individuals, collectives, and
      culture, drawing on literature from social psychology, sociology, economics,
      communication, epidemiology, and other disciplines. Traffic behavior modeling
      could benefit from considering concepts developed in other social disciplines
      while providing challenging research issues and data sources for testing and
      developing those concepts.

PMID- 1388578
TI  - An experimental evaluation of the effects of periodic motor vehicle inspection on
      accident rates.
AB  - 204,000 cars were randomly assigned to three different experimental conditions.
      46,000 cars were inspected annually during a period of three years; 46,000 cars
      were inspected once during three years; and 112,000 cars were not inspected. The
      number of accidents was recorded for a period of four years. No differences in
      accident rates were found between the groups. The technical condition of
      inspected vehicles improved compared to those not inspected. The experiment did
      not have any unintended side-effects. It is concluded that periodic motor vehicle
      inspection has no preventive effect on the technical condition of cars in a
      system where roadside inspections also exist.

PMID- 1388579
TI  - The importance of lower limb injuries in car crashes when cost and disability are
      considered.
AB  - The United Kingdom Cooperative Crash Injury Study (CCIS) database has been used
      to produce a sample of restrained, front-seat car occupants who survived a
      frontal impact. The lower limb was found to be the most frequently injured body
      region in car crashes of all impact types and the second most injured region in
      frontal impacts. 67% of all lower limb fractures in this sample were found to
      occur below the knee. 31% of these fractures occurred at the ankle. A review of
      literature reveals that injury of the lower limb above the knee produces worse
      disabilities and longer recovery times than injury to below the knee. The costs
      incurred as a result of above knee injuries are estimated as being greater than
      those below the knee. A review of European type approval legislation reveals that
      car design is not regulated sufficiently to prevent lower limb injury. Further
      work is suggested using the CCIS database in order to get a better understanding
      of the mechanisms involved with a view to suggesting areas where changes could be
      made to improve this situation.

PMID- 1388580
TI  - A macroscopic impact analysis of the safety efforts case study: pedestrian
      fatalities.
AB  - Any time there are reductions in accidents, advocates of any particular position
      are quick to claim that it is their "effect" that has improved safety
      performance. The work in this paper focuses on interpreting a traffic system's
      performance with respect to a specific type of accident by attributing a change
      in the number of accidents to the relative contribution of three effects: the
      activity effect, the safety content effect, and the structure effect. A method is
      developed and applied to the data sets of pedestrian fatalities that occurred in
      Greece during the period of 1965-1989. The relative contribution of the effects
      as well as the pattern changes turn out to have a decisive influence. The
      possible uses and extensions of the method are also discussed.

PMID- 1388581
TI  - Rural motor vehicle crash mortality: the role of crash severity and medical
      resources.
AB  - We did a retrospective case control study to examine the relationship between the
      risk of dying for Michigan motor vehicle crash (MVC) drivers and the type of
      county (rural/nonrural) of crash occurrence, while adjusting for crash
      characteristics, age, sex, and the medical resources in the county of crash
      occurrence. The 1987 Michigan Accident Census was used to obtain data regarding
      all MVC driver nonsurvivors (733) and a random sample of all surviving drivers
      (2,483). County of crash occurrence was defined as rural or nonrural. The crash
      characteristics analyzed were vehicle deformity, seat belt use, and drivability
      of the vehicle from the scene. Age and sex of the driver were also analyzed.
      Medical resource characteristics for the county of crash occurrence were measured
      as the number of resources per square mile for each of the following: ambulances,
      emergency medical technicians (EMT), acute care hospital beds, and operating
      rooms, surgeons and emergency physicians. Also considered were the number and
      level of emergency rooms in the county of crash occurrence along with the maximum
      level of prehospital care available (basic life support versus advanced life
      support) in a county. Before adjusting, the relative risk (RR) for rural MVC
      drivers dying, compared to their nonrural counterparts, was 1.96. Adjustment for
      crash characteristics, age, and sex (using logistic regression) decreased the RR
      to 1.51. An attempt to add medical resource variables to the model resulted in
      high correlation with the rural/nonrural variable, as well as with each other.
      This multi-collinearity prevented us from providing a simple explanation of the
      role of medical resource variables as predictors of survival.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1388582
TI  - The influence of safety belt laws on self-reported safety belt use in the United
      States.
AB  - We assessed rates and trends in safety belt use by presence and type of safety
      belt law using data from states participating in the 1984-1989 Behavioral Risk
      Factor Surveillance System. State(s) with a safety belt law allowing law
      enforcement officers to stop vehicles for occupants' failure to use safety belts
      (primary enforcement law) had greater and more rapid increases in safety belt use
      rates than did states with laws requiring that vehicles must first be stopped for
      some other violation before a citation or fine for occupants' failure to use
      safety belts could be imposed (secondary enforcement law). Larger and sustained
      increases in safety belt use occurred when safety belt laws became effective or
      when fines were imposed for violations than when laws were first enacted. These
      data suggest that primary enforcement laws result in greater and more rapid
      increases in safety belt use than do secondary enforcement laws, and that initial
      increases in safety belt use following implementation of laws are sustained.

PMID- 1388584
TI  - Extra enforcement and the use of seat belts by drivers in Illinois.
AB  - The use of seat belts by drivers was measured in three target and three control
      cities in Illinois before, during, and after the application of heightened police
      enforcement of the seat belt law in the target cities. The extra enforcement
      produced increases in the use of seat belts by drivers during the four months of
      the heightened enforcement. Observations of seat belt use continued for four
      months after the end of the enforcement, and a substantial residual effect
      remained in two of the three target cities. In one target city the use of seat
      belts had dropped close to the level at the start of the project by the end of
      the second month after the end of enforcement. Taking account of the percentage
      of drivers who became aware of the increased enforcement suggested that a
      sustained program of enforcement may result in 60%-70% of drivers using seat
      belts.

PMID- 1388583
TI  - The influence of flight experience on midair collision risk perception.
AB  - Although successful collision avoidance is presumed a learned skill, midair
      collision accidents typically involve highly experienced pilots. It is
      hypothesized that pilot complacency, arising from a history of incident-free
      flights, plays a role in the midair collision process. Pilot risk perception is
      explored using Laplace's Law of Succession, and the resulting perceived collision
      probability compared to reality. The two converge at around 5,000 hours of flight
      experience.

PMID- 1388585
TI  - Macro model prediction of elderly people's injury and death in road traffic
      accidents in Croatia.
AB  - The case of elderly people injured and killed in traffic accidents in Croatia is
      used to illustrate a prediction method. This method consists of several steps.
      First, the most important variables are selected. Second, to overcome
      intercorrelation, new variables are constructed that include the old ones. Third,
      the new variables and its first derivatives are used in a rank correlation
      method. The results show good predictive capabilities.

PMID- 1388586
TI  - The urban setting of juvenile pedestrian injuries: a study of behavioural ecology
      and social disadvantage.
AB  - Population-adjusted rates of fatal and serious pedestrian injuries (in 435
      Calgary residents age 0 to 17) and some other indicators of behavioural problems
      (including juvenile delinquency) and social indicators (including poverty and
      proportions with low birth weight) were compared across 120 neighbourhoods. Two
      areas with high rates of pedestrian injury, delinquency, and various indicators
      of disadvantage were identified, one close to the city core and the other in
      modern, low-income housing on the city periphery. The patterning of injury rates
      by income levels across neighbourhoods supports earlier Canadian work. Once
      again, a multivariate, causal model of stress and vulnerability in coping with
      physically hazardous traffic environments is implied. Social intervention and
      community development models based on social work research are advocated.

PMID- 1388587
TI  - Time vs. distance as measures of exposure in driving surveys.
AB  - A survey of drivers carried out in Ontario in 1988 has provided data on time
      spent driving as well as the distances driven for licensed drivers of both sexes
      in six age groups and three regions. Substantial differences were found in times,
      distances, and distance/time ratios among these groups. Men drove 50% greater
      distances, but spent only 30% more time driving than women; speed, averaged over
      each day's driving, was lower for older drivers than for younger drivers.
      Differences in speed reflect differences in the driving done in urban or rural
      areas, and differences in the opportunity for road crashes; such differences,
      whether based on units of time or distance, will also affect both the comparisons
      of accident rates and the perceptions of risk among different groups of drivers.
      A definition of exposure to risk of road crash is required that considers both
      time and distance appropriately.

PMID- 1388588
TI  - Causes of nonfatal injuries in the United States, 1986.
AB  - During the 1986 National Health Interview Survey (NHIS), data on injuries
      resulting in a doctor visit or restricted activity for at least a half day were
      collected and assigned E-codes. Based on 603 injuries, the estimated number of
      nonfatal injuries for civilian, noninstitutionalized U.S. residents in 1986 was
      60,212,000. The most frequent cause of injury was a fall (11,547,000), followed
      by motor vehicle traffic crashes (4,361,000) and adverse effects of drugs and
      biologics (3,363,000). While cause-specific detail was limited by small numbers
      of injuries in the sample, the NHIS can provide a valuable snapshot of the causes
      of nonfatal injuries.

PMID- 1388589
TI  - Establishing relationships between accidents and flows at urban priority road
      junctions.
AB  - This papers explores the effects of traffic stream flows on accident potential at
      urban priority-controlled (i.e. unsignalized), four-arm junctions. Forty-three
      urban priority junctions were carefully selected so that other than flow
      parameters expected to influence accident potential have similar values at the
      junctions considered. Using traffic accident data for five-year time periods and
      the corresponding 24-hour flows, a new exposure index is proposed consisting of
      an expression of the flows of the junction's interacting traffic streams. The
      regression of this exposure index on the expected number of accidents per year at
      junctions of the type examined yields a quite satisfactory correlation
      coefficient, better than those achieved when other proposed indices are used.

PMID- 1388590
TI  - Synthesis and pharmacological evaluation of 2,3-dialkylindoles, "in vitro"
      inhibitors of thrombin-induced platelet aggregation.
AB  - A series of 2,3-dialkylindoles (1-5) have been prepared and tested as
      antithrombotic agents. The whole class showed in vitro interesting activity in
      the inhibition of thrombin-induced aggregation. Among these compounds some ones
      showed activity comparable to standards also in the inhibition of collagen
      induced aggregation. Owing to a very fast metabolic degradation through a beta
      oxidative mechanism, a drastic decrease of activity in several tests ex vivo or
      in vivo was observed.

PMID- 1388591
TI  - Synthesis and cardiotonic activity of 2-substituted 5-cyano-1,6-dihydro-6-oxo-3
      pyridinecarboxylic acids and their methyl or ethyl esters.
AB  - The synthesis of ethyl or methyl esters of 5-cyano-1,6-dihydro-6-oxo-3-
      pyridinecarboxylic acids carrying as 2-substituent a polar group such as CO2C2H5,
      (CH2)2CO2CH3, (CH2)3CO2C2H5, CH2OCH3, or CF3 group is described. Also 2-[5-cyano
      1,6-dihydro-2-(1,1-dimethylethyl)-6-oxo-3-pyridyl]-2- oxoacetic acid and 2,5,6,8
      tetrahydro-2,5-dioxo-1H-thiopyrano[3,4-b]pyridine-3-carbon itrile were prepared.
      Nearly all the above esters gave routinely the corresponding carboxylic acids by
      alkaline hydrolysis followed by acidification. As milrinone analogues, the above
      compounds were tested on contractile activity and frequency rate of spontaneously
      beating atria from reserpine-treated guinea-pigs. 5-Cyano-2-trifluoromethyl-1,6-
      dihydro-6-oxo-3-pyridinecarboxylic acid and, in a lesser degree, the relative
      ethyl ester showed an appreciable positive inotropic activity, although inferior
      to that of milrinone.

PMID- 1388593
TI  - Synthesis and pharmacological activity of 4-carbamoyl-5-aryl-6-methyl-4,5
      dihydropyridazin-3(2H)-ones.
AB  - A new series of 4-carbamoyl-5-aryl-6-methyl-4,5-dihydropyridazin-3(2H)-ones have
      been synthesized and tested for their antiinflammatory and analgesic properties.
      Amongst the test compounds, only 31 showed antiinflammatory activity, though of
      shorter duration than that of indomethacin, taken as reference drug. On the
      contrary, many derivatives displayed relevant analgesic activity, 4--the only 4,5
      dehydroderivative--being the most potent in the writhing test. In the hot plate
      test 3b, 3f and 3k were found to possess the most significant analgesic
      properties.

PMID- 1388592
TI  - Synthesis of substituted DL-3(5-benzazolyl)alanines as dopa and alpha-methyldopa
      analogs and their effects on dopamine beta-hydroxylase, tyrosinase and
      diphenoloxidase.
AB  - The influence of bioisosteric replacement of catechol moiety of L-Dopa and alpha
      Methyldopa with benzimidazole and benzotriazole ring has been examined on
      dopamine beta-hydroxylase and tyrosinase, in order to evidentiate an inhibitory
      activity on the synthesis of catecholamines and a possible antihypertensive
      action. The preliminary results obtained so far showed that inhibition of
      dopamine hydroxylase occurs at 5 x 10(-4) M concentration for the most active
      compounds bearing a trifluoromethyl group in the azole ring (2a,c). An analogous
      result was observed in the case of tyrosinase inhibition with compound 2c, while
      other compounds (2a,e) were equiactive (92% inhibition) at higher concentration
      (1 x 10(-3) M). Compound 2c was also the most active in inhibition of
      diphenoloxidase (83% at 6 x 10(-5) M concentration).

PMID- 1388594
TI  - Synthesis and pharmacological study of some 3-(isoxazol-5-yl)-quinazolin-4(3H)
      ones.
AB  - A number of new 3-(isoxazol-5-yl)-quinazolin-4(3H)-ones was prepared and tested,
      together a few analogues previously obtained, for their analgesic, antipyretic
      and antiinflammatory activities, as well as for their acute toxicity and
      ulcerogenic effects. In the carrageenan rat foot edema model one of the tested
      compounds showed activity and LD50 comparable to that of ASA, but the ulceration
      index approximated zero value.

PMID- 1388595
TI  - Styryl and azastyryl 1,3-benzazoles with antihelminthic activity.
AB  - New 2-benzylideneimino- and 2-styryl-1,3-benzimidazole and benzothiazole
      derivatives have been prepared and tested in vitro against Caenorhabditis
      elegans, and Heligmosomoides polygyrus, showing some of them, interesting
      properties as inhibitors, which were not observed in the complementary in vivo
      tests. In order to rationalize the activity, log P was measured for all
      compounds, and QSAR models were developed, allowing the optimisation of the in
      vitro activity.

PMID- 1388597
TI  - Studies about the oral bioavailability of mitonafide and 2HCl amonafide, two new
      cytotoxic molecules.
AB  - A study was done on the factors which could modify the oral bioavailability of
      two new cytotoxic molecules (mitonafide and 2HCl amonafide) when administered in
      solid form. From the values of the ionization constants, we can assume that the
      absorption of these drugs is produced in the first segments of the small
      intestine. In the course of both molecules through the digestive tract to the
      site of absorption, we presume that their chemical stability will not be
      significantly compromised by the influence of pH of the GI tract. The high
      aqueous solubility of 2HCl amonafide and the rapid dissolution rate of mitonafide
      at low pH values lead to assume that the previous dissolution of the drugs will
      not be an essential factor in the absorption of the oral form.

PMID- 1388596
TI  - Benzimidazole condensed ring systems. 8 (1). Synthesis of some substituted 1-oxo
      1H,5H-pyrido[1,2-a] benzimidazole-4-carbonitriles with anticipated antimicrobial
      activity.
AB  - As a part of research project on the syntheses of a number of pyrido[1,2
      a]benzimidazole derivatives with possible antimicrobial activity, some 3-(chloro
      or morpholino)-acetyloxy (2,3), 3-(N,N-dimethylcarbamoyloxy) (4,5) and 3-tosyloxy
      1-oxo-1H,5H-pyrido[1,2a]benzimidazole-4-carbonitrile s (6) were prepared and
      evaluated for such activity. Many compounds exhibited in vitro antimicrobial
      activity and structure-activity relationship is discussed.

PMID- 1388598
TI  - Bioactive polymers. 70. The kinetics of controlled release of neomycin in an
      alkaline medium.
AB  - Neomycin is coupled on xanthan--a polysaccharide of microbial biosynthesis
      produced by Xanthomona campestris--through ionic complexation. The kinetics of
      neomycin release, in vitro, at pH = 8.2 is studied. A release of neomycin,
      following a zero order kinetics, is observed, regardless of the eluent flow-rate.
      The neomycin-xanthan complex, protected by a cellulosic membrane, behaves like a
      monolithic-type device. Diffusion coefficients--increasing with increasing the
      eluent flow-rate--are also calculated.

PMID- 1388599
TI  - Antispasmodic activity of tert-aminoalkylderivatives of 3-benzyl-, 3-benzylaza-
      and 3-benzyldiazaquinoxalinones.
AB  - Tert-aminoalkylderivatives of quinoxalin-2-ones, aza- and diazaquinoxalin-2-ones
      bearing in position 3 a benzyl group were assayed to evaluate the antispasmodic
      activity. The tested compounds exhibited moderate aspecific antispastic
      properties that do not warrant further investigation.

PMID- 1388600
TI  - Synthesis and ADA inhibitory activity of new 2-aryl-8-azaadenosines. VIII.
AB  - Title compounds were synthesized from the protected beta-D-ribofuranosyl-1-azide,
      the sodium salt of malononitrile and the suitable aroyl nitrile. The deblocked 8
      azaadenosines had shown good activity as inhibitors of adenosine deaminase (ADA)
      and a non-substrate behaviour toward the hydrolytic deamination promoted by the
      enzyme.

PMID- 1388601
TI  - 4-(1,2-Benzisothiazol-3-yl)alkanoic and phenylalkanoic acids: synthesis and anti
      inflammatory, analgesic and antipyretic activities.
AB  - Continuing their studies on benzisothiazolyl derivatives, Authors refer to the
      preparation and pharmacological properties of 4-(1,2-benzisothiazol-3-yl)
      alkanoic and phenylalkanoic acids. All substances were tested for anti
      inflammatory, analgesic and antipyretic properties. As reference compounds, 1,2
      benzisothiazolin-3-one and 4-(3-oxo-1,2-benzisothiazolin-3-yl) phenylacetic acid,
      as prototypes of benzisothiazolinonic derivation. Ibuprofen, as a prototype of
      substituted arylalkanoic acids, and Phenylbutazone were used. Analysis of the
      data leaded to the following conclusions. Introduction of the aryl moiety,
      passing from benzisothiazolylalkanoic to benzisothiazolyl-phenylalkanoic
      structures, produced a remarkable increase of activity. 2-[4-(1,2-benzisothiazol
      3-yl)phenyl] propionic and 2-[4-(1,2-benzisothiazol-3-yl)phenyl]butyiric acids
      showed anti-inflammatory, analgesic and antipyretic properties comparable to
      those of Ibuprofen. Substantial differences in variations in activities were
      observed comparing the properties of benzisothiazolylphenylalcanoic acids with
      those of the benzisothiazolinonic series, object of preceding studies.

PMID- 1388603
TI  - Synthesis of phenothiazine derivatives as potential inhibitors of phospholipase
      C.
AB  - In order to study the structure-activity relationships of phenothiazine
      derivatives inhibiting phosphatidylinositol-specific phospholipase C (PI-PLC),
      the synthesis of some phenothiazine amide, amine and ester derivatives was
      performed mainly by reacting 10H-phenothiazine-10-propanoyl chloride with some
      amines and alcohols; the resulting amides were reduced with borane to yield the
      corresponding amines. Starting from 2-chloro and 2-trifluoromethyl-10H
      phenothiazine-10-propanoyl chloride two amides were synthesized. The inhibiting
      activity on PI-PLC from human platelets is reported.

PMID- 1388602
TI  - 4-substituted 1-methyl-1H-indazoles with analgesic, antiinflammatory and
      antipyretic activities.
AB  - The synthesis of [(1-methyl-1H-indazol-4-yl)oxy]acetic acid 4, 1-methyl-1H
      indazole-4-acetic acid 9, 2-(1-methyl-1H-indazol-4-yl)propanoic acid 15 and
      [[(1,5,6,7-tetrahydro-1-methyl-4H-indazol-4-ylidene)amino]oxy]acet ic acid 16, as
      well as of amides and esters derived from 4 and 9, starting from 1,5,6,7
      tetrahydro-1-methyl-4H-indazol-4-one is described. Some of the above compounds
      showed weak antiinflammatory, analgesic, antipyretic and hypotensive activities
      in rats and mice, as well as moderate platelet antiaggregating effects in vitro.

PMID- 1388604
TI  - Synthesis and antimicrobial activity of some thiazolinyl
      tetrahydrobenzo[b]thiophenes and thiazolinyl tetrahydrobenzothieno[2,3
      d]pyrimidin-4-ones.
AB  - Two series of novel 3-carbethoxy-2-(3',4'-disubstituted-2',3'- dihydrothiazol-2'
      ylidenamino)-4,5,6,7-tetrahydrobenzo[b] thiophenes (3a-o) and 2-methyl-3-(3',4'
      disubstituted-2',3'-dihydrothiazol-2'-ylidena mino-5,6,7,8-
      tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H) ones (8a-o) have been synthesized and
      tested for antimicrobial activity. All members of the series have been found to
      exhibit in vitro antibacterial and/or antifungal activities. Activity was
      optimized by cyclization to the thienopyrimidin-4-ones. In particular, compounds
      8e and 8fd were the most active against the 3 tested microorganisms. Their
      antifungal activity was higher than that exhibited by nystatin while their MIC
      was found to be nearly equal to that of nystatin.

PMID- 1388605
TI  - Antibacterial and antiproliferative activities of vulpinic acids in vitro.
AB  - The antimicrobial and antiproliferative activities of vulpinic acids (1 a, b, c)
      have been assayed in vitro. Activity was demonstrated by vulpinic acids on Gram
      positive bacteria only. The MIC values of these compounds were found to be
      ranging from 3.8-31.5 micrograms/ml. The significance of these results is
      discussed.

PMID- 1388606
TI  - An evaluation of structure-penetration relationships in percutaneous absorption.
AB  - Prediction of chemical transport across skin is important both to the
      optimization of topical and transdermal drug delivery and to the assessment of
      risk following dermal exposure. To facilitate estimation of percutaneous
      absorption, a number of model in vitro experimental systems have been developed.
      However, the predictive applicability of the different approaches (with respect
      to human skin penetration), and the quantitative aspects of the structure
      permeation behavior revealed, have not been critically evaluated. The objectives
      of this paper are to collect, from the literature, the more systematic
      investigations pertaining to chemical transport across the skin, to quantify the
      dependence of permeation on the lipophilicity of the penetrants studied, and to
      assess the relative utility of model systems for the prediction of percutaneous
      absorption. The categories of chemicals addressed in the survey include n
      alkanols, para-substituted phenols, steroids and non-steroidal anti-inflammatory
      drugs. The experimental systems, used in the studies considered, involve,
      primarily, steady-state transport measurements across excised skin taken from
      either human cadavers or hairless mice. Favorable comparisons of these data to
      solute flux across simple organic liquid membranes are possible. Overall, general
      patterns of behavior emerge from the analysis such that qualitative predictions
      can be made. From a quantitative standpoint, though, it is clear that additional
      "structure-activity" work is necessary to provide appropriate equations that can
      relate penetration between different test systems and between different chemical
      classes.

PMID- 1388607
TI  - Halogenated isoniazid derivatives as possible antitubercular and antineoplastic
      agents. Note 1.
AB  - Halogenated arylhydrazones, 2-aryl-4-thiazolidinones and their 1,1-dioxides
      containing isoniazid (INI) moieties were prepared and explored for antimicrobial
      (against bacteria, Candida and mycobacteria) and antitumor activities. None of
      the tested compounds showed any marked antimicrobial effect. Furthermore, among
      the compounds submitted to NCI in vitro primary antitumor screening, those
      bearing 3-fluoro or -chlorophenyl substituents were found to possess selective
      inhibitory effects on the growth of non small cell lung cancer, whereas those
      with para-phenyl substituents displayed selective effects, sometimes
      statistically significant, against leukemias.

PMID- 1388608
TI  - Fluorocontaining D-cycloserines. Synthesis and in vitro evaluation of
      antimicrobial and antiviral activities.
AB  - Some fluoroacylderivatives at the side chain NH2 of D-cycloserine were
      synthesized and evaluated in vitro for antimicrobial activity against bacteria
      and tubercular or non-tubercular mycobacteria. Against the used Gram-positive and
      Gram-negative strains only trifluoroacetamide 1 exhibited comparable MIC values
      and lower MBC values than those of parent antibiotic. Other fluoroacycloserines,
      inactive at all on these bacteria, were found to inhibit the growth of
      mycobacteria when tested in liquid media. The in vitro anti-Herpex Simplex virus
      type-2 (HSV-2) activity was also investigated on HEp-2 and Vero cells. The
      obtained results demonstrated an antiviral activity of the compounds 1 and 3 when
      tested on Vero cell-lines, whereas the same cycloserine is inactive.

PMID- 1388609
TI  - Research on heterocyclic compounds, XXIX. Synthesis and antiinflammatory activity
      of imidazo[1,2-a]pyrazine derivatives.
AB  - The reaction in anhydrous ethanol of some substituted 2-aminopyrazines with ethyl
      2-benzoyl-2-bromoacetate or with ethyl 3-bromo-4-oxopentanoate afforded a group
      of ethyl 2-phenylimidazo[1,2-a]pyrazine-3-carboxylates and a group of ethyl 2
      methylimidazo[1,2-a]pyrazine-3-acetates, respectively. The corresponding acids
      obtained via alkaline hydrolysis were subjected to pharmacological testing in
      vivo in order to evaluate their antiinflammatory activity.

PMID- 1388611
TI  - Recombinant human basic-fibroblastic growth factor: different medical dressings
      for clinical application in wound healing.
AB  - Recombinant human basic-Fibroblastic Growth Factor (rhb-FGF) is a basic single
      chain protein showing high activity as mitogenetic and angiogenetic agent. The
      application of rhb-FGF in wound healing as stimulator of the tissue repair
      process is strictly connected with the covering of the wound by means of a proper
      dressing. A wide number of synthetic occlusive or non-occlusive wound dressings
      has been developed. Owing to the delicate proteic structure of rhb-FGF, and
      generally of all the Growth Factors, compatibility with the dressings has to be
      every time tested, to avoid its inactivation and consequent loss of tissue repair
      properties.

PMID- 1388610
TI  - Research on heterocyclic compounds. XXX. Synthesis and pharmacological activity
      of 2-methylimidazo[1,2-b]pyridazine-3-carboxylic acids.
AB  - A group of ethyl 2-methylimidazo[1,2-b]pyridazine-3-carboxylates were prepared by
      reaction in anhydrous ethanol of some substituted 3-amino-pyridazines with ethyl
      2-chloroacetoacetate. The corresponding carboxylic acids were obtained via
      alkaline or acid hydrolysis and then tested both in vivo to evaluate their
      antiinflammatory, analgesic and ulcerogenic actions and in vitro for their
      ability to inhibit the prostaglandin biosynthesis. The pharmacological results
      are discussed in terms of both structure-activity relationships and mechanism of
      action.

PMID- 1388613
TI  - Comparative study of virulence and virulence factors of Aeromonas hydrophila
      strains isolated from water and sediments of a river.
AB  - Seventy-four strains of Aeromonas hydrophila isolated from water and sediments of
      the River Porma (Leon, N.W. Spain) were characterized biochemically and
      biologically. Fifty-seven strains (77.02%) were virulent for rainbow trout (Salmo
      gairdneri) by intramuscular challenge but showed differing degree of
      pathogenicity which could not be associated with the source. A lack of
      correlation between caseinase, haemolytic and cytotoxic activities of the strains
      and their isolation source was also observed. Only two surface characters,
      acriflavine 0.2% agglutination and non-agglutinating SP-/PAB-phenotypes, were
      significantly associated with water and sediment strains, respectively.

PMID- 1388614
TI  - [Description of Salmonella contamination of industrially made pizza products].
AB  - Based on a impurity of industrial made pizza products with Salmonella it was
      checked to what extent the preparation instructions given by the producer are
      connected with a hygienic risk for the consumers. It can be declared that the
      producer didn't deal with its duty for exactness and that the made controls were
      insufficient.

PMID- 1388612
TI  - Condensation products of 2-amino-3-cyano-4,6-disubstituted pyridine with carbon
      disulfide, thiourea, urea & formamide and their antibacterial activity.
AB  - Some new 5,7-disubstituted pyrido[2,3-d]pyrimidine derivatives have been
      synthesized by the condensation of 2-amino-3-cyano-4,6-disubstituted pyridine
      with carbon disulfide, thiourea, urea and formamide. The structure of these
      products are supported by their IR and 1H-NMR spectra as well as by elemental
      analysis. The compounds have been tested for their antibacterial activity against
      E. coli and S. aureus.

PMID- 1388615
TI  - [Experiences with alkaline filter elution for the detection of DNA damage by
      genotoxic compounds].
AB  - In biological effect monitoring the alkaline filter elution is a suitable method
      to detect DNA strand breakage and cross-linking in peripheral blood lymphocytes.
      We applied this method to three groups of workers occupationally exposed to
      carcinogens: n = 39 welders with exposure to chromium and nickel, n = 20 female
      shoemakers with exposure to benzene and n = 25 disinfectors in hospitals with
      exposure to ethylene oxide. In comparison to standardised control groups our
      results must be interpreted as indicating an increased rate of DNA cross-linking
      in welders and disinfectors whereas the female shoemakers showed an increased
      rate of DNA strand breakage. The differences between the results of the exposed
      groups and the stratified control groups were significant in most cases. We could
      reexamine 6 shoemakers 4 months after cessation of exposure to benzene; at this
      moment the results were indicating a clear decrease of the DNA strand breakage.
      Therefore the method of alkaline filter elution seems to be a valuable tool in
      biological effect monitoring of groups occupationally or environmentally exposed
      to carcinogens, especially if the exposure is low, but persistent over a long
      period.

PMID- 1388616
TI  - Infectious risk of replacing venous catheters by the guide-wire technique.
AB  - During the perioperative period cardiac surgical patients are often monitored by
      pulmonary artery (PA) catheters. This catheter, which is floated through the
      right heart into the pulmonary artery, enables the intensivist to measure and
      calculate indices of myocardial performance. After a variable period of time this
      invasive monitoring can often be abandoned following cardiovascular stabilization
      in these patients, but patients usually still require a central venous (CV)
      access for diagnostic and therapeutic purposes. To place this CV catheter either
      a de novo puncture at a new site or a guide-wire change at the existing exit site
      through the PA catheter in place can be performed. Each de novo puncture is
      associated with a risk of traumatising internal vessels or organs. In contrast,
      guide-wire change avoids this risk but inherits a potential risk of transferring
      bacteria by manipulation of contaminated lines. Our study included 159
      consecutive cardiac surgical patients in whom PA monitoring was established
      preoperatively and terminated within a period of up to 72 hours postoperatively.
      At random the PA catheter was replaced by a CV line either by de novo puncture or
      by guide-wire change. All CV lines were left in place for 7 days according to
      standard practice in our intensive care unit (ICU). After removal of CV catheters
      all catheter tips were cultured semiquantitatively by rollplate technique
      according to Maki (26) and subsequent immersion broth culture. A positive culture
      was defined as growth of one up to 15 colonies on the agar-plate or any microbial
      growth in the broth. A significant colonization was assumed in catheters yielding
      more than 15 colony forming units (cfu) on the blood agar plate (26). Our results
      show a significant risk of colonization and catheter-related infection associated
      with the guide-wire technique as opposed to the de novo puncture. The figures for
      relevant colonization were 33.3% in the guide-wire group as opposed to 10.5% in
      the de novo group. However, this difference was noted only in the subgroup in
      which replacement of PA catheters by CV catheters was performed beyond 48 h after
      initial insertion of PA catheters. Within the time intervals of 24 and 25 to 48
      h, respectively, we could not detect any significant difference between groups.

PMID- 1388617
TI  - [Effectiveness of instrument disinfectants under increased protein exposure and
      for standing times up to two weeks].
AB  - To examine the possibility of prolongation of the standing times of instrument
      disinfectants, in vitro tests under high albumin exposure and tests in clinical
      practice were done. Concerning in vitro tests: The bactericidal effectiveness of
      7 commercial preparations for instrument disinfection with different basic
      substances was determined in quantitative suspension tests and of 8 preparations
      in practice-oriented tests according to the guidelines for testing and approval
      of instrument disinfectants by the DGHM (German Society for Hygiene and
      Microbiology). Tests were carried out under increased albumin exposure and at
      prolonged standing times up to 12 days. The instrument disinfectants showed
      microbicidal efficacy up to 12 days at working concentrations slightly increased
      in relation to the concentrations listed by the DGHM. Concerning tests in
      clinical practice: In 4 clinical wards (intensive care unit, cystoscopy unit,
      urological operation unit, gastroenterological endoscopy unit with ERPC) the
      preparations for instrument disinfection were tested up to 12 days in respect to
      the protein exposure and the disinfecting activity of the working solution. The
      working solution was not renewed during the 12 days. The inserted instruments
      were recorded. Concentration of the disinfectants and the protein concentration
      were daily determined. Disinfecting activity was examined by practice-oriented
      microbiological tests. The highest protein exposure was 0.098% after a standing
      time of 12 days. A loss in concentration of disinfectants could not be found.
      Nevertheless independent from the protein exposure there was a loss in
      disinfecting activity of the tap water diluted specimens from the clinical
      practice. Loss in activity could not be seen in the specimen from laboratory
      parallel tests, which were diluted by water of standard hardness. The loss in
      disinfecting activity of the tap water diluted preparation from the
      gastroenterological endoscopy unit versus a dilution by water of standard
      hardness could be confirmed in control experiments (practice-oriented tests with
      S. aureus over a period of 5 days).

PMID- 1388618
TI  - [Mercury concentration in blood and urine--before and after the placement of
      dental amalgam fillings].
AB  - 70 patients of dentist's surgery were given MOD amalgam fillings (non-gamma-2
      amalgam) for molars. They were allocated for comparison to four groups defined by
      their treatment, i.e. the number of old and new restorations and whether a rubber
      dam was used. Blood and urine samples were collected at regular intervals before
      and during a 14-day period after treatment and tested for mercury concentration
      (Hg). Over the observation period the groups with the highest exposure (1-2 old
      restorations replaced by new ones) showed a tendency, in contrast to the less
      exposed groups (1 new filling with or without dam), towards increases (p less
      than 0.10) in group average Hg values of approx. 0.2 microgram/L (blood) and 0.3
      microgram/g creatinine (urine) as acute treatment effects. The highest values
      recorded before and after the treatment, 3.3 micrograms/L (blood) and 16.5
      micrograms/L (urine) are higher than normal but do not indicate any increase in
      the risk to health especially if they are not persistent.

PMID- 1388619
TI  - [RoTrac capillary pore membranes for laboratory filtration. I. Degermination
      filtration].
AB  - RoTrac capillary pore membranes (CPM) are produced by means of the nuclear track
      technology. Thus a defined and in wide ranges independent adjunction of the
      different membrane parameters (diameter, density, shape and inclination of pores)
      is possible. The wanted uniform separation diameter of the membrane can exactly
      be chosen according to the size of the microorganisms to be rejected. By dead end
      filtration experiments with E. coli and Serratia marcescens the suitability of
      RoTrac-CPM in bacteria removal filtration was proven. Blocking was very strong
      for membranes with pore diameters in size range of the microorganisms
      (approximately 0.45 micron). Though the filtrate had immense reduced bacteria
      counts (from 10(7)-10(8) to 10-100 bacteria/ml), it was generally not sterile.
      For membranes with a pore diameter of 0.2 micron and smaller blocking was
      essentially lesser. Here filtrate was always sterile. Flux (and thus the
      filterable volume) corresponds to values of competitive membranes. Compared with
      those the proven possibility of simple cleaning is an advantage, because
      rejection and blocking of symmetrical CPM occur directly on the membrane surface.
      This is promising for use of CPM in cross flow filtration.

PMID- 1388620
TI  - An enzymatic procedure for the confirmation of total coliforms and Escherichia
      coli enumeration from water.
AB  - A new procedure for the confirmation of total coliforms and Escherichia coli from
      presumptive most probable number (MPN) test is described. The procedure utilizes
      an enzymatic test apparatus composed of a couple of devices, one charged with
      ONPG-medium for the detection of beta-galactosidase, the other with PNPG-medium
      for the detection of beta-glucuronidase. The results obtained demonstrate that
      the procedure is sensitive, specific and accurate. Further, it presents some
      advantages from the practical point of view: the cost of the devices is
      relatively low, their use is extremely simple and short time consuming, a single
      thermostatic apparatus adjusted at 36 degrees C for the incubation of the devices
      is only required, the results can be obtained after 18 h without any apparatus
      for the lecture (e.g. UV apparatus), they are not submitted to subjective
      interpretation.

PMID- 1388622
TI  - Nonwoven wound care products.

PMID- 1388621
TI  - Mitraflex wound dressing.

PMID- 1388623
TI  - Effects of helium-neon laser on wound healing.

PMID- 1388624
TI  - AHCPR update. Treatment of urinary incontinence.

PMID- 1388626
TI  - The use of intrasite gel in healing open sternal wounds.

PMID- 1388625
TI  - Cost-effective technology for pressure relief.

PMID- 1388628
TI  - Dibenzo[a,g]quinolizin-8-ones: synthesis, estrogen receptor affinities, and
      cytostatic activity.
AB  - A number of acetoxy-substituted dibenzo[a,g]quinolizin-8-ones were synthesized by
      the reaction of 1-oxoisoquinolines with substituted homophthalic acid anhydride.
      All of the derivatives with acetoxy groups in positions 3 and 10 bind to the
      estrogen receptor. Relative binding affinities (RBA) ranged from 1.8 to 5.6
      (estradiol: RBA = 100) when the substituent at C-6 was a short alkyl group.
      Introduction of additional oxygen functions in the 2- and/or 11-position
      decreased binding affinities. Analyses of the enantiomers of 6-methyl (6b) and 6
      ethyl (6c) derivatives revealed that the receptor binding is mainly due to one
      optical isomer (e.g. (-)-6b, 9.9; (+)-6b, 0.6). In hormone-sensitive human MCF-7
      breast cancer cells, compounds with one acetoxy group in each aromatic ring
      strongly inhibited cellular growth. Despite marked differences in receptor
      affinity, the enantiomers displayed similar activities in this cell culture. In
      hormone-independent MDA-MB 231 mammary tumor cells, only a weak cytostatic effect
      was recorded at 10(-5) M. In the immature mouse uterine weight test, minimal
      estrogenic activity was observed. At higher doses, a significant anti-estrogenic
      effect became evident. It is assumed that the estrogen antagonism is responsible
      for the specific cytostatic effect in MCF-7 breast cancer cells.

PMID- 1388627
TI  - A jejunal fistula in a granulating wound and jejunal refeeding.

PMID- 1388629
TI  - Synthesis and biological evaluation of a series of flavones designed as
      inhibitors of protein tyrosine kinases.
AB  - A series of flavones has been prepared, which are variously substituted in the
      3,3',4',5 and 7 positions with halo-, alkoxy-, nitro-, amino-, hydroxy-, acyloxy-
      and azido-groups, for evaluation of their cytotoxicity to ANN-1 cells (3T3 murine
      fibroblasts transformed with the Abelson murine leukaemia virus) which contain a
      tyrosine kinase. This cytotoxicity was compared to their non-transformed 3T3
      counterparts. 3'-Amino-4'-methoxyflavone was the most cytotoxic compound (IC50 =
      1.6 microM) and was less inhibitory to the non-transformed parent 3T3 cell line
      (IC50 = 8 microM). The compound was inactive at 50 microM in assays of the
      inhibition of the cell-associated Abelson protein tyrosine kinase but inhibited
      an epidermal growth factor (EGF) protein tyrosine kinase by 42% at 50 microM.
      Quercetin (3,3',4',5,7-pentahydroxyflavone) was the most potent inhibitor of the
      Abelson protein tyrosine kinase but showed no selective inhibition of the growth
      of ANN-1 cells compared to the parent 3T3 cell line. Different structure-activity
      relationships were observed between the results of the cytotoxicity assays and
      inhibition of protein tyrosine kinases. Inhibitors of the Abelson protein
      tyrosine kinase which were competitive with respect to ATP showed different
      potencies for inhibition of the EGF receptor kinase.

PMID- 1388630
TI  - Synthesis, DNA binding interactions and biological activity of bis platinum (II)
      complexes of N,N,N',N'-tetrakis(2-aminoethyl)diamines.
AB  - A series of dimers of the monofunctional platinum species [Pt(dien)Cl]+, linked
      by a variety of flexible (polymethylene) and more rigid chains, was prepared and
      evaluated for DNA interactions and cytotoxic activity. The polymethylene-linked
      dimers were prepared by acylation of N(1),N(3)-bistrityldiethylenetriamine with
      alpha, omega-dicarboxylic acid chlorides, followed by reduction with diborane.
      Platination of these ligands was achieved with K2PtI4 prepared in situ, followed
      by anion exchange. Solutions of the bis(Pt(dien)Cl)2+ complexes were stable, and
      shown to be pure by 195Pt NMR, but solid products could not be isolated. All of
      the bis(Pt(dien)Cl)2+ complexes unwound closed circular supercoiled DNA more
      efficiently than the monomer, and were more efficient than the difunctional
      platinum complex cisplatin at cross-linking linearized plasmid DNA, as measured
      on non-denaturing agarose gels. None of the bis(Pt(dien)Cl)2+ complexes were as
      cytotoxic as cisplatin in both the wild-type and platinum-resistant P388 murine
      leukaemia cell lines. The more rigid analogues were equitoxic in both sensitive
      and cisplatin-resistant cells, but none showed in vitro activity against the P388
      tumour.

PMID- 1388631
TI  - Structure-activity relationships for substituted 9-oxo-9,10-dihydroacridine-4
      acetic acids: analogues of the colon tumour active agent xanthenone-4-acetic
      acid.
AB  - A series of 9-oxo-9,10-dihydroacridine-4-acetic acids (acridone-4-acetic acids)
      were prepared by Jourdan-Ullmann condensation of 2-halobenzoic acids with 2
      aminophenylacetic acids, followed by H2SO4-induced cyclodehydration of the
      resulting 2-[2-(carboxymethyl)phenylamino]benzoic acids. These were evaluated for
      their ability to induce haemorrhagic necrosis in transplanted colon 38 tumours in
      mice, using a short-term histology assay. The results broadly paralleled those
      seen previously for xanthenone-4-acetic acids, with 1-, 2- and 7-substitution
      being dystherapeutic, and substitution at the 5- and 6-positions by lipophilic
      groups increasing activity. While some analogues were as active as xanthenone-4
      acetic acids in the histology assay and gave significant growth delays against
      colon 38 tumours in vivo, as a class the 9-oxo-9,10-dihydroacridine-4-acetic
      acids were generally less potent than the xanthenone-4-acetic acids.

PMID- 1388632
TI  - Role of lipophilicity in the in vitro antitumour activity of a series of new
      mitosene compounds.
AB  - The antitumour activity of a series of mitosene compounds in various in vitro
      tumour models was evaluated in terms of physico-chemical parameters.
      Lipophilicity, measured as log P, seemed to be important for in vitro antitumour
      activity in three different cell lines. The in vitro activity of this series of
      mitosenes in an A204 and a L1210 cell line demonstrated a clear bilinear
      dependence on log P with optimal activity at log P values of 2.8 and 3.3
      respectively. Compounds not able to be activated to bifunctional alkylating
      species did not fit into this correlation. Although mitosenes have to be
      activated reductively to alkylating species, no correlation was found between the
      half-wave reduction potential (E 1/2) and the in vitro activity. This lack of
      correlation may be caused by the relatively small range of E 1/2-values within
      this series of mitosene compounds. Our results indicate that penetration of the
      antitumour mitosenes into the cell and the site of activation is an important
      process that leads to antitumour activity and that within the range of compounds
      studied the structural variations are less important for bioreductive activation.

PMID- 1388633
TI  - Rational design of immunotoxins: current progress and future prospects.
AB  - Immunotoxins are hybrid protein molecules created by the chemical or genetic
      fusion of an antibody and a protein toxin. Advances in the molecular engineering
      of monoclonal antibodies and toxins now permit the generation of a variety of
      immunotoxin types with properties optimized for the therapy of different
      malignancies. Novel research promises a new generation of protein therapeutics in
      which the properties of intravascular transport, selective cell binding,
      internalization, translocation to the cytosol, subcellular localization and
      selective catalytic action can be manipulated to order. Immunotoxins that combine
      selective tumour binding with a tumour-specific mechanism of action, such as
      enzymatic inactivation of cellular products responsible for maintaining the
      malignant state, could have a potent and selective anti-tumour action.

PMID- 1388634
TI  - Avian scleroderma: evidence for qualitative and quantitative T cell defects.
AB  - T cell activation is dependent upon calcium influx and protein kinase C
      activation, with subsequent lymphocyte proliferation dependent upon IL-2.
      Abnormalities in T cell proliferation, including abnormal calcium influx and
      defective protein kinase C activation, have been identified in aged mice and
      humans and many autoimmune diseases including diabetes, lupus and scleroderma.
      Since UCD line 200 chickens, which spontaneously develop a scleroderma-like
      disease, have both thymic defects and a diminished peripheral blood lymphocyte
      response to IL-2, we have further investigated T cell function in these birds.
      Interestingly, line 200 T cells respond poorly in vitro to a variety of diversely
      acting T cell mitogens including concanavalin A, phytohemagglutinin and anti
      chicken CD3 monoclonal antibody. Moreover, they do not respond well even to
      phorbol myristate acetate in conjunction with ionomycin. Addition of exogenous IL
      2-containing supernatant concurrently with mitogenic stimulation also had no
      significant effect. Analysis of intracellular free calcium demonstrated that the
      lymphocytes from diseased birds had a reduced influx of calcium (or release for
      intracellular stores) following stimulation. These data clearly reflect a unique
      defect in T cell activation associated with avian scleroderma. Analysis of
      chicken CD3, CD4 and CD8 expression revealed a 39% decrease in peripheral blood
      CD4+ cells in scleroderma birds, although this decrease was not sufficient to
      explain the 80-90% decrease observed in proliferation assays and calcium influx.
      Our data support the hypothesis that avian scleroderma is mediated via abnormal
      function of lymphocyte co-stimulatory molecules or intracellular calcium
      regulators.

PMID- 1388635
TI  - The murine Sm-D autoantigen: multiple genes, genetic polymorphism, evolutionary
      conservation and lack of intervening sequences in the coding region.
AB  - Antibodies to the Sm nuclear antigen are diagnostic of systemic lupus
      erythematosus (SLE). MRL/Mp-lpr/lpr mice develop a similar illness, and a
      proportion also develop anti-Sm. To understand better anti-Sm reactivity in this
      murine model, we have cloned the murine Sm-D autoantigen. One cDNA clone was 517
      bp long with an open reading frame of 357 nucleotides, encoding a 13.3 kDa
      protein of 119 amino acids. At the nucleotide level, the murine Sm-D cDNA was
      89.8% homologous with human Sm-D (94% in the coding region), yet there was
      identity at the protein level, including a Gly-Arg nine-fold repeated C-terminus
      motif. Southern blot analysis of PstI-digested genomic DNA from seven mouse
      strains demonstrated a 7.8 kb band in every strain; in addition, a 2.8 kb band
      was seen in AKR/J, LG/J and MRL/Mp-lpr/lpr. PCR amplification of genomic DNA
      showed a single Sm-D gene product of 360 bp, which indicated a lack of
      intervening sequences. The Sm-D protein is thus highly conserved in evolution,
      probably owing to its essential role in the physiology of the cell.

PMID- 1388636
TI  - The requirements for growth of in vivo activated autoimmune B cells are similar
      to those of in vitro generated lipopolysaccharide B cell blasts and dissimilar to
      anti-IgM plus IL-4 induced B lymphoblasts.
AB  - The requirements for growth of in vivo activated B cells (natural blasts) from
      autoimmune NZB/W mice and of B cells from the same animals activated in vitro
      with either LPS or anti-IgM plus IL4 (mimicking 'in vitro' antigen induced TH
      cell-B cell interaction) were studied comparatively. The proliferation of natural
      and LPS blasts was inhibited by anti-IgM antibodies and augmented by recombinant
      IL-5. In contrast, anti-IgM stimulated the growth of anti-IgM plus IL-4 primed B
      cells but was without effect on the proliferative responses in the presence of IL
      5. The growth inhibition induced by anti-IgM signalling on natural and LPS blasts
      seemed to be due to cross-linking of sIg rather than to binding of anti-IgM
      antibodies to the Fc receptors since a similar effect was observed with the
      F(ab)'2 fragment of this molecule. Maximum proliferation was obtained by a
      combination of IL-4 and IL-5 in natural and LPS blasts, whereas peak responses in
      anti-IgM plus IL-4 blasts were achieved by a combination of anti-IgM and IL-4.
      Lymphoblasts recovered after preculturing natural blasts in medium alone (more
      differentiated in vivo activated B cells) displayed high spontaneous
      proliferation which was strongly inhibited by anti-IgM. This inhibition was
      reversed partially by IL-4 and totally by IL-5. To define better the role of BLy+
      cells in the spleen of NZB/W mice, purified Ly1+ and Ly1- cells, obtained by
      separation using magnetic beads, were analysed. The growth of both cell
      subpopulations was inhibited by anti-IgM and enhanced by IL-5. Cytotoxic
      elimination of Ly1+ cells from the primed B blast populations did not modify the
      proliferative pattern of these cells. Our results show that the growth
      requirements of in vivo activated autoimmune B cells resemble those of LPS blasts
      and differ from those following stimulation with anti-IgM plus IL-4, suggesting
      that B cells in systemic autoimmune diseases may have been activated by
      polyclonal stimulation. Nevertheless, other mechanisms for autoimmune B cell
      activation cannot be ruled out by the present experimental approach.

PMID- 1388637
TI  - Quantitative analyses comparing all major spleen cell phenotypes in BB and normal
      rats: autoimmune imbalance and double negative T cells associated with resistant,
      prone and diabetic animals.
AB  - The BB rat is a model of spontaneous autoimmune diabetes. To characterize
      quantitatively all known immune cell subsets involved in disease pathogenesis,
      FACS analysis of spleen cells was performed in diabetes-prone (DP) and acutely
      diabetic (D) BB rats and compared with diabetes-resistant (DR) BB and normal
      Wistar-Furth (WF) strains. We observed increased percentages of splenic NK cells
      in DP and D animals compared with DR rats using an NK-specific monoclonal
      antibody. We found increased proportions of splenic macrophages in the T
      lymphopenic DP and D rats and low macrophage contents in DR spleens compared with
      WF spleens. We observed that percentages of the CD4-CD8- T cell receptor
      alpha/beta+ (double-negative) T cell subset were strikingly increased in the
      lymphopenic DP and D animals, compared with DR animals. We observed increased
      percentages of activated splenic CD5+ T cells expressing the IL-2 receptor and
      MHC class II antigen in DP and D rats compared with DR animals. Our studies
      suggest that (a) splenic NK cells and macrophages quantitatively appear to be
      involved in the pathogenesis of diabetes; (b) double-negative T cells escape from
      the T cell depletion process; (c) a marked increase of activated splenic T cells
      suggests diabetes is associated with general T cell activation processes; and (d)
      an altered balance among the different immune cell subsets may in part explain
      the pathogenesis of diabetes, since marked relative changes are observed when
      comparing the DR strain to the DP strain in both the prediabetic and diabetic
      stages.

PMID- 1388638
TI  - Rheumatoid arthritis synovial fluid enhances T cell effector functions.
AB  - Rheumatoid arthritis is a chronic autoimmune joint disease of unknown etiology. T
      cells are believed to be important in the pathogenesis of rheumatoid arthritis
      since they infiltrate the joints and express several activation markers, such as
      MHC class II and IL-2R. In this study we have elucidated the effect on freshly
      isolated T cells of rheumatoid arthritis synovial fluid (RA-SF), which contains
      in vivo produced cytokines and enzymes. The mouse mixed lymphocyte culture (MLC)
      has been used as a model and specific cytotoxicity was evaluated against 51Cr
      labelled sensitive target cells. Studies have shown that RA-SF contains a B cell
      differentiation activity that can cross-react between the human and murine
      species. Here we have shown that the addition of RA-SF strongly potentiates
      cytotoxic activity as well as lymphokine production by allogeneic activated
      effector T cells. The enhanced cytotoxicity induced by RA-SF was found to be due
      to a combined effect of increased cytotoxic T lymphocyte (CTL) precursor
      frequency, measured by limiting dilution analysis, and a more efficient killing
      on a per cell basis. Kinetic studies show that RA-SF must be added within 48 h
      after initiation of the MLC, otherwise the effect is lost. The target cell
      specificity of RA-SF was studied, using enriched CD4+ or CD8+ responder cells in
      the MLC. It was found that RA-SF could act directly on the CD8+ cells and
      potentiate their development to cytotoxic effector cells: this activity was not
      found when CD4+ responder cells were used instead. RA-SF could, on the other
      hand, greatly enhance IL-2 production by CD4+ responder cells. We suggest that B
      and T cell activity in RA-SF is important in the propagation of chronic
      inflammation in the joints of patients with rheumatoid arthritis.

PMID- 1388639
TI  - Use of a molecularly cloned human SS.B antigen to detect anti-SS.B antibodies.
AB  - The aim of this study was to examine the utility of diagnostic assays based on
      recombinant SS.B/La (rSS.B). Using this antigen, we have developed an ELISA and
      an immunoblot and compared these recombinant antigen-based assays with
      traditional thymus extract-based counterimmunoelectrophoresis (CIEP). Using the
      recombinant ELISA, the incidence of anti-SS.B in 184 normal blood donors was 2.2%
      (four sera). These four sera were all low titre, i.e., 3-5 SD above the mean. Of
      38 sera positive for anti-SS.B by CIEP, 37 were positive in both recombinant
      assays (97.4% concordance). Anti-SS.B titre in CIEP correlated strongly with
      results of the rSS.B-based ELISA, but the ELISA was 3,000-fold more sensitive. In
      an analysis of 152 autoimmune sera containing anti-DNA, anti-RNP, anti
      centromere, anti-SS.A/Ro or anti-cardiolipin, all of which were negative for anti
      SS.B/La by CIEP, the recombinant assays detected 17 new anti-SS.B positives.
      These positive results were found only in sera which had previously been
      characterised by CIEP as anti-SS.A/Ro positive. Anti-SS.B/La antibodies detected
      by recombinant SS.B assays were found to be highly predictive of primary
      Sjogren's syndrome. Our results show that rSS.B can have an important role in the
      design of sensitive and specific assays for anti-SS.B. The diagnostic
      significance of anti-SS.B/La as a guide to primary Sjogren's syndrome is not
      diminished by the increased sensitivity of recombinant SS.B assays.

PMID- 1388640
TI  - Evidence that a putative anti-idiotypic monoclonal antibody may actually be
      recognizing circulating immune complexes.
AB  - Murine monoclonal antibodies (mAb) reacting with affinity-purified antihistone
      antibodies (AHA) from serum of a patient with systemic lupus erythematosus (SLE)
      were obtained. One of them, 8B3, was initially considered to recognize idiotypic
      (Id) determinants in AHA since (a) it reacted with AHA but not with control IgG;
      (b) this reactivity could be inhibited using affinity-purified AHA, but not with
      control IgG or whole serum; (c) affinity-isolated 8B3+ antibodies showed
      antihistone activity and not other activities tested so far; (d) antihistone
      activity due to 8B3+, but not that of 8B3- from the same serum, could be fully
      inhibited by the presence of 8B3 mAb in the antihistone assay and (e) serum
      levels of 8B3 reactivity were higher than normal in SLE patients with AHA (56%),
      in contrast with SLE patients without AHA (6%). From these results it was deduced
      that 8B3 defined a cross-reactive Id shared by a subset of AHA in SLE patients.
      However, the present results suggest that (a) 8B3 mAb did not recognize AHA or
      Ig, but did recognize a 55 kDa histone-binding protein; (b) this 55 kDa protein
      was present free at low concentration in all human sera, but also associated with
      IgG in 8B3+ SLE sera and (c) these complexes are responsible for the false
      positive results in the antihistone assay as shown for DNA/anti-DNA complexes.
      Thus, mAbs recognizing the non-Ig moiety of circulating immune complexes may
      resemble anti-Id antibodies with features of the so-called epibodies. These
      immune complexes may be responsible for false positive results and caution should
      be exercised in the interpretation of results.

PMID- 1388641
TI  - Expression of inactive stage anti-dsDNA idiotypes on anti-ssDNA antibodies in a
      lupus patient during active stage of lupus cerebritis.
AB  - The possibility that idiotypes (Ids) defined on anti-double stranded DNA (dsDNA)
      antibodies during active and inactive stages of lupus (1/84 Id and 4/90 Id,
      respectively) were expressed on anti-DNA antibodies during a subsequent active
      period (9/90) of the disease was investigated in a lupus patient with lupus
      cerebritis. Using rabbit (R)-anti-Ids specific to 1/84 Id and 4/90 Id in
      inhibition assays, the 4/90 Id was shown to be expressed on the framework regions
      of anti-single stranded DNA (ssDNA) but poorly on co-existing anti-dsDNA
      antibodies of active (9/90) stage. The 1/84 Id was poorly expressed on both types
      of 9/90 anti-DNA antibodies. While the 9/90 anti-ssDNA significantly bound to
      immobilized ssDNA and several single-stranded polynucleotides, only ssDNA
      inhibited the binding of the anti-ssDNA to ssDNA, suggesting its monospecificity
      toward ssDNA. Western blot analysis following isoelectric focusing showed that a
      spectrotype pattern of 4/90 Id-positive 9/90 anti-ssDNA IgG was similar to that
      of the 4/90 anti-dsDNA, suggesting that they are of related clonal origin. The
      present study suggests the idiotypic heterogeneity of anti-DNA antibodies and the
      shift of antigen specificity within an idiotypically related anti-DNA population
      during exacerbation of the disease.

PMID- 1388642
TI  - Galactose terminating oligosaccharides of IgG in patients with primary Sjogren's
      syndrome.
AB  - Using a simple but novel ELISA, we have screened 40 serum samples from patients
      with primary Sjogren's syndrome and 34 normal controls for IgG glycosylation
      deficiencies, identified by their specific ricin binding. Elevated levels of
      asialylated IgG were detected in 24 patients. The extent of asialylation was
      significantly higher in the patients with extraglandular manifestations than in
      the others. Interestingly, the correlation of asialylated IgG was apparent only
      with Raynaud's phenomenon and arthritis, and not other extraglandular
      manifestations. Strong correlations (P less than 0.01) were noted between
      asialylated IgG and rheumatoid factor or IgA-containing immune complexes.

PMID- 1388643
TI  - Intravenous cocaine challenges during desipramine maintenance.
AB  - Intravenous challenges with placebo and cocaine doses ranging from 0.125 to 0.5
      mg/kg were administered to five subjects using a within subjects design during
      placebo and active desipramine (DMI) maintenance at a fixed dose of 150 mg daily
      for at least 10 days. The "high" reported after cocaine infusion was not altered
      by DMI, but "desire for cocaine" after a single dose was attenuated. Together
      with the results of clinical trials of DMI for cocaine abuse, these laboratory
      results suggest that DMI may reduce cocaine craving both during and between
      cocaine binges. Physiologically, baseline heart rate was higher on DMI, but the
      incremental heart rate response to cocaine was attenuated.

PMID- 1388644
TI  - Selective breeding for increased cholinergic function: biometrical genetic
      analysis of muscarinic responses.
AB  - Biometric genetic analyses of behavioral and physiologic responses known to be
      related to muscarinic cholinergic receptors (hypothermia, hypoactivity, inhibited
      avoidance, and reduced responding for water) were studied in genetic crosses and
      backcrosses of the Flinders sensitive line (FSL) and Flinders resistant line
      (FRL) of rats. The FSL rats were more sensitive to the direct muscarinic
      agonists, arecoline and oxotremorine, and to the indirect agonist, physostigmine,
      than any other group. The next most sensitive group was the F1 x FSL backcross,
      followed by the F2, F1, F1 x FRL backcross, and the FRL, in that order. These
      differences between the genetic groups could be accounted for completely by
      either solely additive or additive plus dominance genetic factors. When dominance
      genetic factors contributed to the differences among groups (6 out of 15), the F1
      responded like the FRL rats. The variance of the responses measured made it
      impossible to obtain reliable estimates of the number of genes involved in many
      instances; when such estimates were possible, several genes (greater than or
      equal to 3) appeared to be involved. We conclude that muscarinic sensitivity in
      rats is under genetic control, with the greatest contribution coming from
      additive genetic factors. Because the FSL rat appears to be a genetic animal
      model of depression, the finding of several genes influencing muscarinic
      responses may help account for the difficulties investigators have had in
      locating a single major gene or biological marker for human depressive disorders.

PMID- 1388645
TI  - Bromocriptine reverses the elevation in intracranial self-stimulation thresholds
      observed in a rat model of cocaine withdrawal.
AB  - Cocaine use frequently occurs in episodic prolonged binges. Following such a
      cocaine binge, the user suffers from severe depression mixed with irritability,
      anxiety, anergia and anhedonia. These symptoms constitute the cocaine withdrawal
      syndrome. Since cocaine's rewarding effects are mediated by enhanced dopaminergic
      neurotransmission in the mesocorticolimbic system, it is possible that a long
      acting dopamine agonist might block the withdrawal effects associated with the
      termination of a prolonged bout of cocaine self-administration. An animal model
      of post-cocaine anhedonia was developed using the elevation in intracranial self
      stimulation (ICSS) thresholds following the termination of prolonged periods of
      cocaine self-administration as a measure of an animal's "anhedonic" state. In the
      present study, an attempt was made to reverse the postcocaine elevation in ICSS
      thresholds with acute administration of a dopaminergic agonist, bromocriptine.
      Rats were allowed to self-administer cocaine for 24 hours continuously. Four
      hours after the termination of the self-administration session, animals were
      injected with either vehicle or bromocriptine (1, 2, or 4 mg/kg, IP). Two hours
      later (6 hours post cocaine), the animals' self-stimulation thresholds were
      assessed. Confirming previous work, treatment with the vehicle following a
      cocaine "binge" resulted in elevated ICSS thresholds compared to predrug baseline
      levels or to control rats' thresholds. Bromocriptine, at doses that had no effect
      on ICSS thresholds in control rats, reversed the postcocaine anhedonia in a dose
      related manner. These results indicate that bromocriptine-like drugs
      (pharmacological agents that enhance dopaminergic neurotransmission) may be able
      to ameliorate some of the effects of cocaine withdrawal on mood and motivational
      state. In addition, the results of the present study indicate that the proposed
      animal model of cocaine withdrawal could be useful in the discovery and
      development of new pharmacotherapies for cocaine withdrawal.

PMID- 1388646
TI  - Cerebral glucose metabolism in patients with summer seasonal affective disorder.
AB  - Positron emission tomography scans of nine patients diagnosed with summer
      seasonal affective disorder (SSAD) were compared with scans of 45 normal control
      subjects to investigate differences in brain glucose metabolism. All subjects
      performed an auditory discrimination task beginning several minutes before
      injection of F-18-deoxyglucose and continuing for 30 minutes after injection.
      Regional glucose metabolic rates were extracted from 60 rectangular regions of
      interest measured in five planes selected as atlas matches from 28 total slices.
      Statistically significant differences between patients with SSAD and normal
      control subjects were found in cerebral glucose metabolic rate and also in
      normalized regional glucose metabolic rates in the orbital frontal cortex and in
      the left inferior parietal lobule.

PMID- 1388647
TI  - Human hallucinogen interactions with drugs affecting serotonergic
      neurotransmission.
AB  - The absence of relevant human research studies of hallucinogenic drugs has not
      curtailed their unsupervised use. Two cases are presented that suggest decreased
      sensitivity to the serotonergic hallucinogens psilocybin and LSD induced by drugs
      with effects on serotonergic neurotransmission, allopurinol and fluoxetine. These
      reports suggest that hallucinogens' effects in humans are mediated by
      serotonergic receptors.

PMID- 1388648
TI  - Suppressor T cells: some answers but more questions.
AB  - Many properties of suppressor T cells and the antigen-binding factors derived
      from them have evaded molecular genetic definition. Here, Martin Dorf and
      colleagues discuss recent data in the context of a growing awareness of the
      molecules and principles involved.

PMID- 1388649
TI  - NK cells and T cells: mirror images?
AB  - The expression of MHC class I molecules protects cells against lysis by natural
      killer (NK) cells. It is possible that NK cells are 'educated' to recognize self
      MHC class I molecules and that the combination of self peptide and MHC class I
      molecule blocks NK-mediated lysis. Here, Rogier Versteeg compares and contrasts
      models of education and self-nonself discrimination by T cells and NK cells, and
      presents a hypothesis for the evolution of T cells from NK cells.

PMID- 1388650
TI  - One explanation for F1 antiparent responses.
AB  - The phenomenon of hybrid resistance, in which F1 offspring reject parental
      grafts, remains a perplexing problem. Here, Tina Dalianis and Lars Ahrlund
      Richter propose that one component of the F1 antiparent response results from
      competition between the two sets of parentally derived major histocompatibility
      complex (MHC) molecules for 'promiscuous' peptides. Lack of tolerance in the F1
      animal results from insufficient presentation of these peptides on the MHC
      molecule that has lower affinity for the peptides.

PMID- 1388651
TI  - Immunosuppression by ultraviolet B radiation: initiation by urocanic acid.
AB  - Irradiation with UV-B, a component of natural sunlight, initiates systemic
      immunosuppression of delayed-type hypersensitivity responses. This may be a
      fundamental regulatory mechanism, controlling the interaction between mammals and
      potentially deleterious environmental UV radiation. Here, Frances Noonan and
      Edward De Fabo assess the evidence that suppression is initiated by the
      photoisomerization of trans-urocanic acid (UCA) in the stratum corneum, discuss
      the significance of this mechanism for skin cancer outgrowth and propose
      applications for UCA in transplantation.

PMID- 1388652
TI  - Autoimmunity and the ovary.
AB  - The ovary was first documented as a target of autoimmunity over three decades ago
      yet today the aetiology and pathogenesis of autoimmune-mediated premature ovarian
      failure (POF) are poorly understood. Here, Roy and Helga Moncayo provide a brief
      overview of human autoimmune-mediated POF and the animal models of POF. They
      propose a model for the development of the disease, highlighting the role of
      supraphysiological levels of gonadotropins in inducing selectively antigenic
      mature ovarian elements.

PMID- 1388653
TI  - Human T-cell activation deficiencies.
AB  - The increasing understanding of T-cell activation is paralleled by the
      recognition of a growing range of 'experiments of nature' that cause T-cell
      activation deficiencies. Analysis of these deficiencies is, in turn, contributing
      to the understanding of T-cell function in vivo. Here, Jose Regueiro, Antonio
      Arnaiz-Villena and colleagues review current knowledge of structural and
      functional T-cell defects and the implications of these for T-cell biology.

PMID- 1388654
TI  - The origin and function of tumor-associated macrophages.
AB  - Tumor-associated macrophages (TAM) have a complex relationship with the
      neoplastic cells of the tumor. On the one hand, the two cell types produce
      reciprocal growth factors and may be considered to have a symbiotic relationship.
      On the other hand, TAM can be activated to inhibit tumor growth and destroy
      neoplastic cells. Here, Alberto Mantovani and colleagues describe this delicate
      balance and the prospects for its therapeutic manipulation.

PMID- 1388656
TI  - HIV TAR and the CD3 gamma chain.

PMID- 1388655
TI  - Lipopolysaccharide antagonists.
AB  - Bacterial lipopolysaccharide (LPS) is a potent and pleiotropic stimulus of immune
      cells. LPS has important clinical relevance because it has a direct role in the
      pathogenesis of Gram-negative bacterial infection. The lipid A moiety of LPS is
      responsible for the toxic effects of LPS. The identification of structural
      analogs and precursors of lipid A, which are apparently competitive antagonists
      of the biological actions of LPS, is strong evidence that the actions of LPS are
      mediated by a specific LPS receptor or family of receptors. Identification and
      analysis of these LPS receptors with LPS antagonists should help to define the
      pathways of cellular activation by LPS and lead to the development of novel anti
      LPS strategies in the therapy of bacterial diseases.

PMID- 1388657
TI  - [Phadiatop in the diagnosis of skin allergy to pneumoallergens].
AB  - Usually, Phadiotop is presented as an in vitro multitest to pneumoallergens that
      are indicated in respiratory allergy. Now, in skin allergy atopic dermatitis and
      reaginic urticaria-Quincke's oedema, the responsibility of pneumoallergens,
      particularly mites, is clear. 47 Subjects were studied. Clinical history, skin
      test nd specific IgE gave confirmation of allergy to pneumoallergens. This was
      proved by the subsequent clinical development, with, in most cases, spectacular
      improvement after desensitization.8 section. We have compared Phadiotop with
      these different clinical criteria, skin tests and Cap Rast IgE. The results
      favour Phadiotop and confirm its value and indication in skin allergy to
      pneumoallergens.

PMID- 1388659
TI  - [Skin tests in allergic vasculitis].
AB  - For etiologic checking of cutaneous vasculitis, skin testing may be of valuable
      help: epicutaneous patch-tests with delayed lecture (48 h.) performed with
      contact haptens (rubber allergens, azo dyes, resins ...) or drugs in pigmented
      progressive purpuric skin eruptions; prick-tests submitted to delayed (6-8 h.)
      clinic and histologic lecture, performed with miscellaneous drug or food-derived,
      microbial or environmental antigens in necrotizing vasculitis. In these
      conditions skin testing should be approached with great caution, because of the
      occurrence of non relevant positive reactions and the risk of precipitation of
      cutaneous or disseminated lesions of vasculitis.

PMID- 1388658
TI  - [Multitest Fx5 in food allergy].
AB  - A comparative study was made of three in vivo and in vitro diagnostic methods for
      food allergy: Fx5 multitest (Pharmacia); Measurement of specific IgE CAP
      (Pharmacia); Skin tests (Prick Tests). 20 patients, from 3 to 71 years (mean 24.4
      years), were selected by clinical suggestion (asthma, rhinitis, atopic
      dermatitis, urticaria and/or Quincke's oedema). The Fx5 test used six food
      allergens: wheat, egg, cow's milk, soya, peanut and fish. The Cap Rast for each
      substance was evaluated, as was Fx5, by a radio-immunological method. The Prick
      Tests made with the six allergens used were considered to be positive when the
      diameter of the weal was greater than that produced by a reference test with
      histamine. The results were considered as a comparison between Fx5 and Cap Rast
      to each of the foods, between Fx5 and prick Test with five foods and finally
      between CAP RAST and Prick Test. Correlation Fx5--Cap rast was better and more
      useful in the diagnosis of food allergy than skin tests.

PMID- 1388660
TI  - Immunologic mechanisms in secretory otitis media--recent concepts. Part I.
AB  - Increasing evidence has been accumulated in the last few years associating
      immunological mechanisms in the pathogenesis of secretory otitis media. If
      immunological processes were found to be involved in both of the previously
      accepted experimental pathogenic models (Eustachian tube obstruction:
      microbiologically induced) of the disease, recently published data has provided
      evidence for a third, not Eustachian tube--or microbiological-dependent,
      exclusively immunological, experimental model. This suggests that immunological
      mechanisms are probably always involved in the pathogenesis of a disease that is
      known to be multifactorial in origin, and thus eventually make Immunology the
      single most important factor in secretory otitis media. In the present article
      these recent concepts are extensively reviewed by the authors.

PMID- 1388661
TI  - [Reevaluation of environmental factors in allergy to mites: bedding not a
      factor?].
AB  - Prospective multicentric study was conducted among parents of children referred
      in three allergy units. Unlike current opinions: carpets are less frequent in
      bedrooms of mite's allergic children. foam bedding don't play any role, local
      humidity non significantly increases the mite's allergy risk. the sunlight
      absence is significantly correlated with this hypersensitivity. These data,
      mainly inconsistent with general conviction, could be explained by socio economic
      diversity of patients.

PMID- 1388662
TI  - [Clinical effectiveness and tolerance of loratadine versus cetirizine in the
      treatment of seasonal allergic rhinitis].
AB  - A double blind multicentre study of seasonal rhinitis (108 patients) has compared
      Loratadine and Cetirizine. The results of clinical scores are significantly good
      for both products. Only tolerance is different and in favour of Loratadine, since
      sleepiness was found in 9.5% of patients treated with Cetirizine, and 3.6% with
      Loratadine.

PMID- 1388663
TI  - Stability of fungal alpha-amylase in sodium dodecylsulfate.
AB  - Unfolding of a fungal alpha-amylase in aqueous sodium dodecylsulfate (SDS)
      solution was examined by SDS-polyacrylamide gel electrophoresis (PAGE). When the
      alpha-amylase was incubated with 1% SDS at room temperature and subjected to SDS
      PAGE, it showed a much higher mobility than expected from the molecular weight.
      Circular dichroic and gel filtration analyses indicated that the protein is
      apparently in the native conformation upon incubation with 1% SDS. When the
      protein was heated in the presence of 1% SDS at 90 degrees C for 10 min, it had a
      lower mobility in SDS-PAGE and showed characteristics of an unfolded protein by
      circular dichroism and gel filtration. The melting temperatures of the protein
      were determined in the absence and presence of SDS by incubating it for 10 min at
      various temperatures. The melting temperatures were 70, 55, and 49 degrees C in
      the presence of 0, 1, and 2% SDS, respectively. The observed small shift of the
      melting temperatures by SDS suggests that the destabilizing action of SDS on the
      alpha-amylase is weak. However, the unfolding in SDS is not reversible process,
      since prolonged incubation of the protein with 1% SDS at 50 degrees C gradually
      increased the amount of unfolded protein. This indicates that the SDS-induced
      unfolding of the alpha-amylase is a slow process.

PMID- 1388664
TI  - Conformation of concanavalin A and its fragments in aqueous solution and organic
      solvent-water mixtures.
AB  - The conformations of concanavalin A (con A), an all-beta protein, and its three
      CNBr-cleaved fragments were studied by CD. Con A in buffer showed a 197 nm
      maximum and a 223 nm minimum, which were red-shifted by 6-7 nm from those of
      regular all-beta proteins and beta-sheet of (Lys)n. Fragment 1 (residue 1-42)
      resembled an unordered form with a CD maximum at 200 nm, but fragments 2
      (residues 43-129) and 3 (residues 130-237) showed a regular CD spectrum with two
      extrema at 192-193 nm (+) and 214-216 nm (-). Equimolar mixture of the three
      fragments showed some degree of interaction, but did not reconstitute the
      conformation of native con A, probably because of the loss of bound Ca2+ and Mn2+
      ions in the fragments. In ethanol-, methanol-, and dioxane-water mixed solvents,
      con A and its fragments remained as beta-sheet. In contrast, addition of
      trifluoroethanol and sodium dodecyl sulfate induced alpha-helix at the expense of
      beta-sheet for con A and its fragments in aqueous solution. In 80%
      trifluoroethanol, the induced helicities exceeded their sequence-predicted helix
      potentials, but in 10 mM sodium dodecyl sulfate the helicities agreed well with
      corresponding predictions.

PMID- 1388665
TI  - Structural analysis of seminal and serum human transferrin by second derivative
      spectrometry and fluorescence measurements.
AB  - Denaturation of human seminal transferrin (HSmT) compared with human serum
      transferrin (HSrT) was followed to check structural differences between these two
      proteins. Second derivative UV spectroscopy indicated that treatment with 6 M
      guanidine hydrochloride (Gnd.HCl) induced greater structural changes in HSrT than
      in HSmT and, in particular; (i) the exposure value of tyrosinyl residues was
      almost 2.5-fold higher in native HSmT than in native HSrT; and (ii) a much more
      pronounced movement of tryptophanyl residues toward a higher polar environment
      could be noticed in HSrT after incubation with denaturing agent. Fluorescence
      measurements showed that: (i) a shift of the maximum emission wavelength of HSmT
      occurred (maximum emission was centered at 333 nm instead of 323 nm as for HSrT;
      excitation = 280 nm); (ii) the intrinsic tryptophan fluorescence intensity of
      HSmT increased after 36 hr in the range of 1.5-4.0 M of denaturant, whereas an
      opposite behavior was found for HSrT in the range 0.0-2.0 M; and (iii) the
      wavelength maximum of fluorescence emission changed in a biphasic manner for HSrT
      and, conversely, under the same experimental conditions, HSmT gave a linear and
      parallel increase of fluorescence emission after 1 and 36 hr. We can conclude
      that this different behavior of HSmT with respect to HSrT might be due mainly to
      the fact that both the number and the exposure of tyrosinyl and tryptophanyl
      residues are different. Lately, these effects are discussed in relationship with
      the fact that HSmT contains less than half disulphide bridges than HSrT.

PMID- 1388666
TI  - Dependence of reaction rate of 5,5'-dithiobis-(2-nitrobenzoic acid) to free
      sulfhydryl groups of bovine serum albumin and ovalbumin on the protein
      conformations.
AB  - The effect of protein conformations on the reaction rate of Ellman's reagent,
      5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) with sulfhydryl (SH) groups of
      proteins was examined. The stopped-flow method was applied to follow the reaction
      of DTNB with SH group of two proteins, bovine serum albumin (BSA) and ovalbumin
      (OVA), at various concentrations of guanidine hydrochloride and urea. The rates
      for both the proteins were faster in guanidine than in urea. The rate sharply
      depended on the protein conformations, which were monitored by changes of helix
      contents on the basis of the circular dichroism measurements. The reaction rate
      of DTNB with SH groups of BSA was maximal around 2 M guanidine and 5 M urea. On
      the other hand, the reaction rate of DTNB with OVA was maximal at 3.5 M
      guanidine, while it gradually increased with an increase in the urea
      concentration. The amount of reactive SH group participating in the reaction with
      DTNB was also estimated by the absorbance change at 412 nm. The magnitudes of
      absorbance change for the reaction with free SH groups of OVA at low
      concentrations of the denaturants were appreciably smaller than those for BSA
      with one free SH group. Most of the four SH groups of OVA might react with DTNB
      above 5 M guanidine, although only a part of them did even at 9 M urea.

PMID- 1388667
TI  - An evaluation of different enzymatic cleavage methods for recombinant fusion
      proteins, applied on des(1-3)insulin-like growth factor I.
AB  - Different enzymatic methods for cleavage of recombinant fusion proteins were
      compared. To find an efficient cleavage method, five different fusion proteins
      were produced. The fusion proteins differed only in the linker region between the
      fusion partner and the desired product, human des(1-3)insulin-like growth factor
      I. A cleavage study was performed with enterokinase, plasmin, thrombin,
      urokinase, and recombinant H64A subtilisin. Significant cleavage was obtained
      using thrombin, H64A subtilisin, and enterokinase. Thrombin cleavage was studied
      on a larger scale and des(1-3)IGF-I was recovered at a final yield of 3 mg/L
      growth medium. Thrombin and enterokinase were also studied as immobilized
      proteases and they cleaved the fusion proteins with retained activity. To further
      improve thrombin cleavage, a continuous reactor was constructed, consisting of a
      closed system with a thrombin column and an ion exchange column in series. Here,
      the fusion protein circulated while free des(1-3)IGF-I was bound to the ion
      exchange column after release from the fusion protein. In the reactor, thrombin
      was as efficient as the free enzyme but gave a diminished rate of product
      degradation.

PMID- 1388668
TI  - In vivo and in vitro methylation of lysine residues of Euglena gracilis histone
      H1.
AB  - We have earlier identified and purified two protein-lysine N-methyltransferases
      (Protein methylase III) from Euglena gracilis [J. Biol. Chem., 260, 7114 (1985)].
      The enzymes were highly specific toward histone H1 (lysine-rich), and the
      enzymatic products were identified as epsilon-N-mono-, di- and trimethyllysines.
      These earlier studies, however, were carried out with rat liver histone H1 as the
      in vitro substrate. Presently, histone H1 has been purified from Euglena gracilis
      through Bio-Rex 70 and Bio-Gel P-100 column chromatography. The Euglena histone
      H1 showed a single band on SDS-polyacrylamide gel electrophoresis and behaved
      like other histone H1 of higher animals, whereas it had a much higher Rf value
      than the other histones H1 in acid/urea gel electrophoresis. When the Euglena
      histone H1 was [methyl-3H]-labeled in vitro by a homologous enzyme (one of the
      two Euglena protein methylase III) and analyzed on two-dimensional gel
      electrophoresis, three distinctive subtypes of histone H1 were shown to be
      radiolabeled, whereas five subtypes of rat liver histone H1 were found to be
      labeled. Finally, by the combined use of a strong cation exchange and reversed
      phase Resolve C18 columns on HPLC, we demonstrated that Euglena histone H1
      contains approximately 9 mol% of epsilon-N-methyllysines (1.40, 1.66, and 5.62
      mol% for epsilon-N-mono-, di- and trimethyllysines, respectively). This is the
      first demonstration of the natural occurrence of epsilon-N-methyllysines in
      histone H1.

PMID- 1388669
TI  - Purification and sequence determination of canine relaxin.
AB  - Relaxin immunological activity has been observed in the plasma of pregnant
      bitches, and preliminary studies in our laboratory indicated that the highest
      relaxin concentrations were found in placentas. Therefore, canine placentas were
      collected at term and also from spay and relaxin was purified by methods
      developed for equine relaxin. Tissue was prepared by homogenization and
      purification on a C18 column. The preparation was further purified by stepwise
      elution ion-exchange chromatography, gel filtration, and gradient elution ion
      exchange chromatography. One predominant peak in relaxin immunoactivity was
      collected. Canine relaxin was found to be larger than either porcine or equine
      relaxin as determined by SDS-PAGE. It migrated faster under reducing conditions,
      indicating a subunit structure. Purified canine relaxin was used for tracer and
      standard in a canine radioimmunoassay (RIA) using an antiporcine relaxin
      antibody. Concentrations of relaxin immunoactivity using the canine assay were up
      to 300-fold higher in placental preparations than those measured in the porcine
      relaxin assay. Sequence analysis of canine relaxin revealed a structure similar
      to other relaxins in the presence and placement of cystine residues.

PMID- 1388671
TI  - Biophysical analysis of phaseolin denaturation induced by urea, guanidinium
      chloride, pH, and temperature.
AB  - The structural stability of phaseolin was determined by using absorbance,
      circular dichroism (CD), fluorescence emission, and fluorescence polarization
      anisotropy to monitor denaturation induced by urea, guanidinium chloride (GdmCl),
      pH changes, increasing temperature, or a combination thereof. Initial results
      indicated that phaseolin remained folded to a similar extent in the presence or
      absence of 6.0 M urea or GdmCl at room temperature. In 6.0 M GdmCl, phaseolin
      denatures at approximately 65 degrees C when probed with absorbance, CD, and
      fluorescence polarization anisotropy. The transition occurs at lower temperatures
      by decreasing pH. Kinetic measurements of denaturation using CD indicated that
      the denaturation is slow below 55 degrees C and is associated with an activation
      energy of 52 kcal/mol in 6.0 M GdmCl. In addition, kinetic measurement using
      fluorescence emission indicated that the single tryptophan residue was sensitive
      to at least two steps of the denaturation process. The fluorescence emission
      appeared to reflect some other structural perturbation than protein denaturation,
      as fluorescence inflection occurred approximately 5 degrees C prior to the
      changes observed in absorbance, CD, and fluorescence polarization anisotropy.

PMID- 1388670
TI  - Pepsin fragmentation of botulinum type E neurotoxin: isolation and
      characterization of 112, 48, 46, and 16 kD fragments.
AB  - Controlled digestion of approximately 150 kD single chain botulinum type E
      neurotoxin with pepsin at pH 6.0 produced 112, 48, 46, and 16 kD fragments. These
      were chromatographically purified; their locations in the approximately 1300
      amino acid residue long neurotoxin were determined by identifying the amino
      terminal 10 residues of 112 and 48 kD fragments, 50 residues of 46 kD fragment,
      and 59 residues of 16 kD fragment. The 48 and 112 kD fragments contain the N
      terminal segment of the neurotoxin (i.e., residue no. 1 to approximately 425 and
      1 to approximately 990, respectively), the 46 kD fragment corresponds to
      approximately 407 residues of the C-terminal region, and the 16 kD fragment
      contains the approximately 140 residues from a segment nearer to the C-terminus.
      The 48 kD fragment is similar to the approximately 50 kD N-terminal light chain
      of the approximately 150 kD dichain neurotoxin, which is generated by tryptic
      cleavage of the approximately 150 kD single chain neurotoxin, and is separated
      from the approximately 100 kD C-terminal heavy chain by dithiothreitol (DTT)
      reduction of an intrachain disulfide bond in the presence of 2 M urea
      (Sathyamoorthy and DasGupta, J. Biol. Chem. 260, 10461, 1985). The pepsin
      generated 48 kD fragment, unlike the light chain, was isolated without exposure
      to DTT and urea. The single chain 112 kD fragment following trypsin digestion
      yielded 48 and 60 kD fragments that were separable after DTT reduction of the
      intrachain disulfide which links them. The N-terminal residues of the smaller
      fragment were identical to that of the single chain 150 kD neurotoxin; the single
      chain 112 kD fragment is therefore the neurotoxin minus the approximately 50 kD C
      terminal half of the heavy chain. The biological activities of the 48 and 112 kD
      fragments can be demonstrated in permeabilized PC12 cells (Lomneth et al., J.
      Neurochem. 57, 1413, 1991); they inhibit norepinephrine release.

PMID- 1388672
TI  - Microenvironment of tryptophan residues in beta-lactoglobulin derivative
      polypeptide-sodium dodecyl sulfate complexes.
AB  - The changes of microenvironment of tryptophan residues in beta-lactoglobulin A
      and its cyanogen bromide (CNBr) fragments with the binding of sodium dodecyl
      sulfate (SDS) were studied with measurements of the rates of N-bromosuccinimide
      (NBS) modification reactions by stopped-flow photometry. Two tryptophan residues
      of carboxyamidomethylated (RCM) beta-lactoglobulin A in the states of their
      complexes with SDS were clearly distinguishable by their differences in NBS
      modification rates. We confirmed by experiments with CNBr fragments containing
      trytophan residue. The modification rates of Trp 19 in RCM beta-lactoglobulin A
      SDS complexes were about 10-fold smaller than those expected for tryptophan
      residues exposed entirely to the aqueous solvent. The Trp 61 was hardly changed.
      The change of rate constants for Trp 19 was virtually consistent with those
      observed when N-acetyl-L-trytophan ethylester was dissolved in SDS micelles. For
      various species of polypeptide-SDS complexes, all tryptophan residues were
      reactive to NBS and also, for some of them, the differences in NBS modification
      rates were observed between tryptophan residues on a common polypeptide chain.
      These results suggest micellar and heterogeneous bindings of SDS to polypeptides.

PMID- 1388673
TI  - Similarity between average distance maps of structurally homologous proteins.
AB  - A similarity between average distance maps (Kikuchi et al., 1988a)--that is,
      predicted contact maps of two tertiary structurally homologous proteins--is
      examined. Comparisons of shapes of average distance maps (we refer to this as
      ADM) are made by superpositions of ADMs for two homologous proteins. Also, we
      compare shapes of actual contact maps for the pair of proteins. We search a
      optimal superposition mode of each pair of maps showing that two proteins are
      most similar. It is concluded that two ADMs are also similar when actual tertiary
      structures between two proteins show similarity. A criterion for similarity of
      maps is also proposed. The possibility of application of this method to detect
      weak homology between protein structures is discussed.

PMID- 1388676
TI  - A customized non-axial external beam technique for treatment of prostate
      carcinomas.
AB  - A nonaxial four-field technique for primary and boost treatment of prostate
      carcinoma has been developed in an effort to minimize dose to rectum and bladder.
      Using a treatment planning CT scan, prostate, rectal and bladder volumes are
      outlined and corresponding three-dimensional structures are created. An oblique
      CT image, which bisects the prostate volume and excludes rectum and bladder, is
      reconstructed. Four beams, consisting of direct laterals and two anterior,
      inferior obliques, are designed, which lie in the plane of the generated image.
      Utilizing a beam's-eye-view display and multilevel dose calculations, blocks are
      designed for each port, which encompass the target volume within a minimum
      isodose surface. These customized angles result in oblique ports with rectal and
      bladder sparing that can be comparable to that of direct lateral ports. Dose
      volume histogram analysis is used to evaluate the merits of this nonaxial method
      with other approaches.

PMID- 1388675
TI  - Rat liver low M(r) phosphotyrosine protein phosphatase isoenzymes: purification
      and amino acid sequences.
AB  - Two low M(r) phosphotyrosine protein phosphatases have been isolated from rat
      liver. The enzymes were previously known as low M(r) acid phosphatases, but
      several recent studies have demonstrated that this family of enzymes possesses
      specific phosphotyrosine protein phosphatase activity. We determined the complete
      amino acid sequences of the two isoenzymes and named them AcP1 and AcP2. Both
      consist of 157 amino acid residues, are acetylated at the NH2-terminus, and have
      His as the COOH-terminus. The molecular weights calculated from the sequences are
      18,062 for AcP1 and 17,848 for AcP2. They are homologous except in the 40-73
      zone, where about 50% of residues are different. This fact suggests that the two
      isoenzymes are produced by an alternative splicing mechanism. There is no
      homology between these two isoenzymes and the receptor-like phosphotyrosine
      protein phosphatases LAR, CD45, human placenta PTPase 1B, and rat brain PTPase-1.
      AcP1 and AcP2 are also distinct from rat liver PTPase-1 and PTPase-2, since these
      last enzymes have higher molecular weights. AcP1 differs from AcP2 with respect
      to (1) substrate affinity and (2) its sensitivity to activators and inhibitors,
      thus suggesting a their different physiological function.

PMID- 1388677
TI  - High dose rate treatment of a maxillary sarcomatoid carcinoma: a case report.
AB  - A 37-year old Native American woman presented with a rare sarcomatoid carcinoma
      of the left maxilla. She underwent extensive resection, but developed an orbital
      cavity recurrence. This was treated with external beam radiation therapy. The
      boost posed dosimetric difficulties due to the anatomic peculiarities of the
      treatment area. Extensive treatment planning for a high dose rate Iridium 192
      source helped overcome these problems. Control of the tumor was achieved in the
      site of recurrence.

PMID- 1388674
TI  - Sequence and structural relationships in the cytokine family.
AB  - The sequences of nine different cytokines, growth hormone, and prolactin have
      been aligned and their secondary structure predicted. The alignment reveals that
      each exon has a characteristic sequence pattern shared by all cytokines. The most
      striking sequence similarity is observed in exon 4, where the residue pair Phe
      Leu is conserved in many cytokines. In addition, there are discreet homologous
      regions between two specific growth factors, including a high degree of homology
      between granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin
      3 (IL-3). The secondary structure analysis predicts that exon 3 of all cytokines
      has an antiparallel helix-turn-helix motif, which is likely to form the central
      helical segments of a four alpha-helical bundle-type structure. Based on the
      secondary structure and the disulfide-bonding pattern, the topological
      connectivity for a number of cytokines has been predicted.

PMID- 1388678
TI  - Immobilization and treatment of patients receiving radiation therapy for
      extremity soft-tissue sarcoma.
AB  - The treatment of extremity soft-tissue sarcoma has evolved considerably over the
      years. Previously, the preferred treatment was radical resection or amputation.
      Recently, radiation therapy combined with conservative resection has been shown
      to provide adequate tumor control while preserving a functional limb. Often, a
      large volume of tissue is irradiated in a manner that requires the patient to be
      in a reproducible position. Minimizing patient movement is imperative to ensure
      that the prescribed dose is delivered to the designated target volume. At our
      institution, Alpha Cradles have been routinely used for eight years to aid in
      positioning extremity sarcoma patients. The positioning of the patient for tumors
      at different locations in the extremity and the Alpha Cradle fabrication is
      described. The positioning device is comfortable for the patient and the accuracy
      is verified by comparison of simulation films with weekly port films.

PMID- 1388679
TI  - Weight consideration in the use of cerrobend beam blocks.
AB  - The technique of using customized field blocking to protect sensitive normal
      tissue during megavoltage radiation treatment is common practice in modern
      radiation therapy. The introduction of CT-based treatment planning has
      revolutionized customized field shaping. We carried out a prospective evaluation
      of 54 cerrobend blocks during a one-month time period. The goals of this study
      were to analyze the specific block patterns and correlate these with field size,
      block weight, and field setup. Factors contributing to excessively large and
      heavy cerrobend blocks defined as > or = 20 lbs. were identified. Twenty-two
      percent of blocks were found to be excessively large and one-third of these were
      a consequence of planning decisions. A review of these situations suggests that
      alternative methods would have avoided the excessive weight. Concerns have been
      raised regarding the safety of large and heavy cerrobend blocks. These blocks
      were therefore analyzed in terms of tray sag and tray break-point. Our data
      suggest that within this clinical range of block weight, neither tray sag nor
      tray break-point are of significant concern.

PMID- 1388680
TI  - Determination of basal dose rates in Paris system of interstitial implants.
AB  - The isodose distributions are related to the source configurations in the Paris
      system of interstitial implants. In this system, the basal dose rates are
      determined at those points identified relative to the implant. Once these points
      have been located, the basal dose rates are merely the summation of the dose rate
      contributions from all the sources. By applying the symmetry properties of the
      implant, the number of basal dose rate computations and the number of dose rate
      summations are reduced. The reduction in both the number of computations and the
      number of summations has facilitated the determination of the average basal dose
      rate. After the average basal dose rate has been determined, the reference dose
      rate that is used clinically is calculated. Examples of determining the basal
      dose rates for a few interstitial implants are presented.

PMID- 1388681
TI  - Verification of treatment plans by mathematical formulas for single catheter HDR
      brachytherapy.
AB  - In high dose-rate brachytherapy, 500 to 1000 cGy will be given in a matter of
      minutes. Therefore, careful treatment planning and accurate verification of the
      plan is critical. To expedite the plan verification procedure, simple
      mathematical formulas were derived in our previous paper for single catheter
      treatments on a Nucletron microSelectron system. In this paper, the usefulness
      and limitations of these formulas for the plan verification procedure are further
      discussed.

PMID- 1388682
TI  - Immobilization and stabilization of testicular clamshell shields in seminoma
      patients.
AB  - It is standard practice when treating the pelvic and para-aortic lymph nodes of
      seminoma patients, to use a method to reduce the dose to the testicles due to
      scattered radiation. A common method is the use of lead testicular shields
      (clamshells). We have developed a method of immobilizing the patient while at the
      same time providing a stable and reproducible position for the testicular shield.

PMID- 1388683
TI  - Electron beam versus photon beam radiation therapy for the treatment of orbital
      lymphoid tumors.
AB  - Shielding the lens of the eye while treating orbital lymphoid tumors and
      achieving a relatively homogeneous dose can be a dosimetric challenge. There are
      many clinical cases of tumors close to one or both eyes, where it is desirable to
      spare the lens as much as possible. We will show isodose curves comparing direct
      anterior fields using various electron beam energies to a single 6 mv photon beam
      to a multifield combination. The presence of an eye shield in a photon beam may
      impair the dose distribution at the back of the eye to an undesirable degree. The
      strong in-depth dose drop-off in electrons and the ease with which the beam can
      be intercepted suggests that an electron beam with an eye shield may offer
      advantages. We designed a suspended movable lens shield .8 cm wide with a height
      of 4.5 cm made of cerrobend surrounded by a brass cylinder mounted to a thin
      plexiglass plate to insert into a Varian electron 6 x 6 cone. A 1.5 cm gap
      between block and eye surface was used. Verification of dose distribution under
      the lens shield was obtained by film dosimetry.

PMID- 1388684
TI  - Stepwise transformation of primary thyroid epithelial cells by a mutant Ha-ras
      oncogene: an in vitro model of tumor progression.
AB  - Activating mutations of the ras oncogene family occur at high frequency in all
      stages of thyroid tumorigenesis, both human and experimental. To test the causal
      nature of this association, and to investigate the biological role of ras
      mutation, we introduced a mutant c-Ha-ras gene into normal rat thyroid follicular
      cells using an ecotropic retroviral vector. The major immediate effect was to
      greatly extend the proliferative lifespan of these cells in culture from less
      than 3 to more than 15 doublings, without any observable loss of growth-factor
      dependence or differentiated functions. This in vitro phenotype strongly supports
      an initiating role for ras mutation in the genesis of benign thyroid tumors
      (adenomas) in vivo. Spontaneous transformation was observed at low frequency on
      continuous culture of mutant ras-expressing cells, giving rise to fully
      immortalized, growth factor-independent, highly tumorigenic lines. Transformation
      was associated with (i) loss of responsiveness to the growth inhibitor TGF-beta
      1, and (ii) greatly increased nuclear levels of p53 protein, which unexpectedly
      was not due to point mutation in the conserved regions of the p53-coding
      sequence. We postulate that these two phenomena are causally related to each
      other and to the transformed phenotype.

PMID- 1388685
TI  - Alternative splicing of neurofibromatosis type 1 gene transcript in malignant
      brain tumors: PCR analysis of frozen-section mRNA.
AB  - The neurofibromatosis type 1 (NF1) gene encodes a 360-residue region showing
      significant homology to the catalytic domains of both mammalian GTPase-activating
      protein (GAP) and yeast IRA protein. The product of the GAP-related domain of the
      NF1 gene (NF1-GRD) has been shown to stimulate ras GTPase and consequently to
      inactivate ras protein. We previously reported that the NF1-GRD has two types of
      transcripts, type I and type II, which are generated by an alternative splicing
      mechanism, and that the differential splicing of the NF1-GRD may be related to
      differentiation of neuroectodermal cells. Here we examined the differential
      expression of type I and type II transcripts of NF1-GRD in clinical samples of
      supratentorial malignant brain tumors by the RNA-polymerase chain reaction (PCR)
      method using frozen tissue sections. Our observations revealed that normal
      cerebrum predominantly expressed the type II NF1-GRD transcript, whereas
      primitive neuroectodermal tumors predominantly expressed the type I transcript.
      Additionally, although the type I/type II ratio in astrocytomas varied widely
      among tissue samples, all glioblastomas showed higher type I/type II ratios than
      adjacent brain samples. The RNA-PCR analysis using frozen tissue sections is a
      useful and sensitive method for detecting genetic markers in clinical tissue
      samples.

PMID- 1388686
TI  - Effect of simultaneous variation of weight, density, temperature and O2
      concentration on rainbow trout (Oncorhynchus mykiss) body composition.
AB  - The simultaneous effect of weight, initial density (kg/m3, temperature and O2
      concentration on rainbow trout body composition (fat, protein, moisture and ash)
      has been studied. In 3 successive experimental phases fish were kept in different
      lots of varying initial weight (178-372 g), initial density (7.2-38.8 kg/m3) and
      temperature (15-20 degrees C). Simple correlations were statistically significant
      for weight vs fat (r = 0.56; P less than 0.001) and moisture (r = -0.57; P less
      than 0.001); temperature vs fat (r = 0.73; P less than 0.001) moisture (r = 
      0.73; P less than 0.001) and ash (r = -0.26; P less than 0.02); and O2
      concentration vs fat (r = 0.22; P less than 0.05). Multivariant equations for the
      different compounds were obtained. Only fat and moisture percentages showed
      significant differences (rm = 0.75; P less than 0.00005); an inverse relation
      existing between them (r = -0.94; P less than 0.001). Temperature is the factor
      which has the strongest influence on fat and moisture when it varies
      simultaneously with weight, initial density and O2 concentration, which is shown
      by its equation coefficients (P less than 0.00005).

PMID- 1388688
TI  - Sleeping distance in relation to sexual state in the Arctic blue fox.
AB  - The paper provides comparative data concerning sleeping distance in relation to
      sexual state and hierarchical dominance in the Arctic blue fox. Increasing levels
      of vulval swelling and electrical resistance of vaginal tract were inversely
      related to sleeping distance between the highest-ranking male and each female on
      heat. A mating pair typically slept no further than 50 cm from each other. One
      month after copulation, the distance was already more than 200-250 cm. It can be
      concluded that oestrus-associated changes in sexual hormone levels have an
      influence on observed changes in sleeping distance.

PMID- 1388687
TI  - Distribution of alpha CDCP-immunoreactive neurons in the central nervous system
      of the snail Helix aspersa.
AB  - alpha CDCP is a neuropeptide produced by the caudodorsal cells of Lymnaea
      stagnalis and encoded by the genes of the egg-laying hormone (ELH). The use of a
      polyclonal antiserum raised against alpha CDCP resulted in the detection of about
      800 immunoreactive neurons in the parietal ganglia and a small population (60
      cells) in the cerebral ganglia of Helix aspersa. As the genes of ELH are well
      conserved among the gastropod species, these data designate the parietal ganglia
      as a putative source for the egg-laying hormone in Helix aspersa.

PMID- 1388689
TI  - Distribution of radioactivity of 14C-amino acids added to the medium in cells and
      metabolites in cultures of rumen fungi.
AB  - A mixture of L-(U-14C) amino acids was added to cultures of 11 strains of rumen
      anaerobic fungi belonging to Neocallimastix frontalis, Neocallimastix joyonii,
      Sphaeromonas communis and Piromonas communis. Fungi were grown in a complex
      medium with glucose for 4 days. The radioactivity was found in cellular protein
      (27.7-65.3% of the total radioactivity recovered), lactate (16.9-41.8%), volatile
      fatty acids (7.4-25.7%) and ethanol (4.6-10.5%). A small amount of radioactivity
      was recovered in lipids (0.2-1.8%) and CO2 (0.3-1.0%). The results suggest that
      the assimilation of amino acids by growing fungal cells was quantitatively
      comparable with their dissimilation to metabolites.

PMID- 1388690
TI  - Growth hormone response to TRH in male broiler chickens selected for body weight
      gain or food conversion and reared at either a moderate or a high ambient
      temperature.
AB  - The aim of the present experiment was to study the growth hormone (GH) response
      upon thyrotropin releasing hormone (TRH) challenge (2 micrograms/kg body weight)
      in broiler chickens selected for body weight gain (GL line: fat line) or for feed
      efficiency (FC line: lean line) reared at either a moderate (33-23 degrees C) or
      high (33 degrees C) ambient temperature. A higher plasma GH level at 5 min after
      TRH administration was observed in the high temperature conditioned chickens of
      both lines. Also at high ambient temperature, an enhanced GH decrease between 15
      min and 30 min post-injection and a higher acute elimination rate was calculated
      compared to moderate ambient temperature. A significantly higher GH secretory
      response was observed in the leaner FC line chickens, which was probably related
      to the more pronounced pulsatory GH secretion rate in these chickens. There was
      no difference in GH acute elimination rate between both lines in both
      environments. No interactions between line and rearing temperature for these
      parameters of GH dynamics were observed.

PMID- 1388691
TI  - Effect of ovarian cystic or haemorrhagic follicles on embryo recovery and
      survival after transfer in hCG-ovulated rabbits.
AB  - The relationship between the presence of cystic and/or haemorrhagic follicles in
      both donor and recipient does and survival at birth of frozen-thawed embryos (778
      embryos transferred) from 3 selected rabbit strains (NZ: New Zealand white; SY
      and SB: synthetic breeds) were studied. Donor does (SY:108; NZ:99; SB:96) were
      mated and treated with 25 IU of hCG. Only morphologically normal oviductal
      morulae (64-66 h) were frozen. Frozen-thawed embryos from each of the 90 donor
      does were transferred into the oviducts of synchronized recipient does of the
      same strain 48 h after injection of 25 IU of hCG (SY:31; NZ:28; SB:31). The
      frequency of follicular anomalies (36 and 43%) was high in both donor and
      recipient does, respectively, and it was not affected by strain or parity. The
      follicular anomalies had a negative effect on the percentage of embryos recovered
      in the oviduct (70 vs 77%) but not on the percentage of recovered embryos
      catalogued as morphologically normal (97%). The absence of follicular anomalies
      in recipient does had a significantly favourable effect on the pregnancy rate (63
      vs 18%; P less than 0.05) and consequently on embryo survival rate at birth (26
      vs 7%; P less than 0.01).

PMID- 1388692
TI  - Bovine cumulus expansion and corona-oocyte disconnection during culture in vitro.
AB  - Cumulus-oocyte complexes were aspirated from small antral follicles (3-5 mm in
      diameter) and divided into 2 groups: complexes in which a dark rim of corona
      cells were visible around the zona pellucida (group 1); and those in which the
      corona displayed the same density as the rest of the cumulus cell mass (group 2).
      Cumulus complexes of both groups were evaluated by acetoorcein staining, scanning
      electron microscopy (SEM) and 3H-uridine uptake during culture in vitro. Germinal
      vesicle breakdown was initiated at 7 h of culture in group 1 while more than half
      of the oocytes in group 2 already displayed germinal vesicle breakdown at the
      time of aspiration. However, whereas more than 80% of the oocytes in group 1 had
      reached metaphase II at 24 h of culture, almost half of the oocytes in group 2
      were arrested in metaphase I after this time interval. As revealed by SEM the
      complexes of group 2 showed signs of expansion such as elongation of cumulus
      cells and presence of extracellular matrix already at the time of aspiration. In
      group 1 these features were noticed at 7-9 h of culture. A high level of
      metabolic coupling between corona cells and oocyte was maintained up to 9 h of
      culture in group 1 followed by a decrease to a constant low level at 13 h. In
      group 2 a high degree of coupling was maintained up to 7 h followed by a gradual
      decrease to a constant low level at 13 h. It is concluded that cumulus-oocyte
      complexes with a dark rim of corona cells as judged by stereomicroscopy mature at
      a higher rate and maintain unexpanded characteristics and efficient corona-oocyte
      coupling longer than complexes with even density of the cumulus mass.
      Consequently, the presence of a dark rim of corona cells may be used as a
      criterion for selection of oocytes for in vitro embryo production.

PMID- 1388693
TI  - Effect of dietary lysine on muscle protein turnover in growing chickens.
AB  - Day-old male chickens were fed ad libitum isoenergetic diets containing 20% crude
      protein but differing in their lysine content (from 6.5 up to 11.3 g/kg). At 3
      weeks of age, protein fractional synthesis rates in the pectoralis major muscle
      were determined using a large dose injection of 120 mumol per kg body weight of L
      [4-3H] phenylalanine. Protein gain in the pectoralis major was measured between
      19 and 23 days of age. Protein breakdown was obtained by calculating the
      difference between protein synthesis and deposition. Weight gain varied
      curvilinearly with dietary lysine intake and was maximum for 11.3 g lysine/kg of
      diet. In birds fed an adequate lysine intake (10.1-11.3 g/kg) protein fractional
      synthesis and breakdown rates were 23.6-25.9 and 17.8-19.8%/d respectively.
      Increasing lysine supplementation in the diet resulted in an impairment of
      protein fractional breakdown rates. By contrast, protein fractional synthesis
      rates remained unchanged owing mainly to an improvement in the synthesis
      efficiency (kRNA), until birds were fed an adequate lysine intake. These data
      suggest that the growth rate reduction of chickens fed lysine deficient diets was
      due to alterations in both rates of protein synthesis and breakdown in skeletal
      muscle. A maximum protein deposition is achieved when kRNA was optimal, ie for a
      dietary lysine content of about 9 g/kg, a value close to the requirement.

PMID- 1388694
TI  - Kinetics of particulate and solute marker passage in sheep supplemented with
      cationomycin and lasalocid antibiotics. Comparisons among methods for calculating
      mean retention time.
AB  - Passage of particulate and solute markers in the digestive tract was studied in
      sheep fed a roughage-pelleted diet supplemented or not with ionophore
      antibiotics. Methods of marker administration (continuous infusion vs pulse-dose)
      and mathematical treatment of data were investigated. Antibiotic supplementation
      did not affect markers' mean retention time (MRT) significantly, regardless of
      sampling site, technique of marker administration or MRT calculation methods
      used. The pulse dose technique led to 20-30% higher estimate of particle markers
      MRT in the entire gut and stomachs of sheep than did the continuous infusion
      method. Similar results were obtained between these methods for solute markers
      MRT at both sampling sites. Total MRT in the digestive tract could be partitioned
      among compartments using a deterministic model when applied to pulse-dose
      kinetics. Such a partitioning appeared unsatisfactory with continuous-infusion
      data. Estimations of particle or solute markers MRT in the rumen from duodenal
      and faecal marker kinetics were significantly different and rarely correlated.

PMID- 1388695
TI  - [Early diagnosis of pregnancy in the cow as assessed by milk ejection induced by
      luteal oxytocin].
AB  - The diagnosis of pregnancy described in this article is based on the observation
      of milk ejection which, in the case of corpus luteum maintenance, results from
      the release of luteal oxytocin induced by intravenous administration of a non
      luteolytic dose of PGF2 alpha. The tests were performed in 410 lactating cows, 18
      22 days after insemination (mean 19.95 days, SD 0.75), 3 h prior to the evening
      milking. A cannula was placed in the left fore-teat; when the cisternal milk flow
      ceased, a small dose of a prostaglandin F2 alpha analogue (256 micrograms
      Dinolytic) was injected. If a corpus luteum was present, the alveolar milk flow
      (1,276 +/- 570 ml) started 86 +/- 35 s later and pregnancy could be presumed. If
      the corpus luteum was no longer functional, the milk flow did not start again and
      the cow was considered not pregnant. The accuracy of positive results, ie 72.3%,
      significantly exceeded that obtained by radioimmunoassay of plasma progesterone
      used as a reference method, ie 68.6% (P less than 0.05). By contrast, the
      accuracy of negative results was lower, ie 93.5 vs 100%, (P less than 0.05): of
      the 195 pregnant cows which proceeded to term, 10 did not respond to the milk
      ejection test. In spite of these reserves, the test has the advantage of being
      inexpensive, rapid (about 5 min) and easy to interpret, ie either the milk flows
      or it does not. In addition, it may be used early, because from day 20 after Al
      the reliability of prediction of non pregnant cows (67.0%) was significantly
      higher when compared to the use of progesterone radioimmunoassay (58.6%) (P less
      than 0.05). With such a test, non pregnant cows can be reinseminated immediately
      and not only after a 3-week period. This may contribute to reducing the length of
      the infertile period.

PMID- 1388696
TI  - Evidence of a contralateral motor influence on reciprocal inhibition in man.
AB  - The role of contralateral movement on both H reflex and reciprocal inhibition was
      studied. In normal men H reflex was induced by median nerve stimulation.
      Reciprocal inhibition was achieved through stimulation of the antagonist radial
      nerve. On this basis the effects of contralateral arm movement were analyzed.
      Furthermore the putative influence of exteroceptive origin was also verified by
      means of digit stimulation. Results showed that contralateral arm movement did
      not affect H reflex amplitude; on the contrary, it was able to enhance reciprocal
      inhibition induced by extensors on flexors. Study of cutaneous afferents
      demonstrated that contralateral digit stimulation failed to elicit modifications
      on both H reflex and reciprocal inhibition. On the other hand, ipsilateral digit
      stimulation lowered H reflex amplitude and increased the degree of reciprocal
      inhibition. Experimental findings underline the possibility that an informational
      array reaches the contralateral IA interneuron: therefore a mutual (bilateral)
      interaction among IA interneurones may accordingly be hypothesised.

PMID- 1388697
TI  - Human brain phenolsulfotransferase. Regional distribution in Parkinson's disease.
AB  - Brain phenolsulfotransferase (PST) in 105.000 x g supernatant fractions prepared
      from post mortem human brain catalyzes the sulfate conjugation of dopamine (DA).
      Using 50 microM DA, the PST activity was linear up to one hour. The KM value for
      DA was 3.1 microM. Higher concentrations of DA from 25 b microM up caused
      inhibition of PST activity. Assessment of regional distribution in normal brain
      using 20 microM DA concentration revealed the highest PST activities in temporal
      and frontal cortex. About ten times lower activities were measured in parietal
      and occipital lobe, amygdala, hypothalamus, and hippocampus, whereas the nucleus
      accumbens, nucleus basalis of Meynert, caudate nucleus, and substantia nigra
      showed the lowest activities (about 1% of those in frontal and parietal cortex).
      In the brains of subjects with Parkinson's disease (PD) treated with levodopa, a
      significant reduction of PST activities was observed in hypothalamus, frontal and
      temporal cortex, amygdaloid nucleus, occipital and parietal cortex (between 20
      and 38.8% of controls). Depletion of PST activity was less severe in hippocampus
      (46% of controls), nucleus accumbens, putamen, and substantia nigra (67 and 72%
      of controls, respectively). No changes were observed in the nucleus basalis of
      Meynert, while PST activity was increased in the caudate nucleus (174 to 203% of
      controls). The presented data indicate that on PD brain the PST activity is
      reduced in areas of the cerebral isocortex and limbic system, while in the basal
      ganglia it is either mildly reduced (putamen) or increased (caudate nucleus).
      Selective changes of PST activity in PD brain may indicate an important function
      of this enzyme in the metabolism and/or storage of DA under pathological
      conditions.

PMID- 1388698
TI  - Efficacy of memantine, an NMDA receptor antagonist, in the treatment of
      Parkinson's disease.
AB  - Memantine is a 1-amino-adamantane derivative which has been proposed to be useful
      in the treatment of Parkinson's disease. Its beneficial effect has been related
      to its novel properties as an NMDA receptor blocker which can neutralize the
      effect of glutamate at striatal and subthalamic levels. In the present study,
      conducted in an open-fashion, 14 parkinsonian patients with motor fluctuations
      taking L-dopa, were given a supplement of memantine 30 mg/day. After one month,
      10 patients completed the treatment (4 discontinued it due to abdominal pain,
      psychomotor agitation, confusion and dizziness). In 5 patients, the main
      parkinsonian features improved significantly (1 point or more on the Webster
      scale). In 6 patients, "off" episodes improved (from daily mean of 273 minutes,
      to 172 minutes). In summary, memantine addition to parkinsonian features, could
      form a basis for novel therapeutic strategies directed to neutralize the effects
      of glutamate at striatal and subthalamic levels.

PMID- 1388699
TI  - Peripheral blood cell activities of monoamine oxidase B and superoxide dismutase
      in Parkinson's disease.
AB  - Monoamine oxidase type B (MAO-B) and superoxide dismutase (SOD) are two enzyme
      systems that are potentially relevant to an oxidative stress model of Parkinson's
      disease (PD) causation. Activities of MAO-B in platelets (nmol/10(8) cells/hr)
      and total SOD in lymphocytes (U/mg protein) were assayed among 28 cases of
      idiopathic PD and 22 controls. As anticipated, MAO-B was lowest in PD cases on
      selegiline (L-deprenyl) therapy (mean 1.10). There was a slight deficit of MAO-B
      among male cases not taking selegiline compared to controls (3.78 vs. 4.15), but
      the opposite trend was observed for females (6.18 vs. 4.16). SOD was slightly
      higher in cases (7.40), than controls (6.81). Excess SOD among PD cases was seen
      irrespective of gender, age, or selegiline treatment, although none of the
      differences was statistically significant. Future research on SOD should take
      advantage of the availability of assays specific for the cytosolic and
      mitochondrial forms of the enzyme.

PMID- 1388700
TI  - Long-term observation of chronic subcutaneous administration of lisuride in the
      treatment of motor fluctuations in Parkinson's disease.
AB  - Twenty-nine patients with advanced Parkinson's disease were treated with
      subcutaneous lisuride infusion in addition to a basic therapy consisting of
      levodopa + PDI in all, and deprenyl in some patients. At the time of the report,
      13 patients are still receiving lisuride infusion after 5-36 months, while 16
      have dropped out after 0.5-30 months: one because of psychosis, three because of
      insufficient efficacy, three due to death unrelated to treatment, three because
      of difficulties in handling the pump as outpatients, and six for other reasons.
      "Off"-periods and Parkinsonian disability in "off" and in "on" were reduced
      significantly. These improvements remained constant throughout the observation
      period. Once the optimal dose regimen is established, only minor adjustments of
      the doses of lisuride and levodopa are required in the individual case.

PMID- 1388701
TI  - Investigation of the mechanism of the effect of tacrine (tetrahydroaminoacridine)
      on the metabolism of acetylcholine and choline in brain cortical prisms.
AB  - The mechanism by which tacrine increases the content and synthesis of
      acetylcholine (ACh) in cerebrocortical prisms exposed to an irreversible
      inhibitor of cholinesterases and incubated under resting conditions (Dolezal and
      Tucek, 1991) is not known. As found in the present experiments, this effect of
      tacrine is only apparent if its application had been preceded by a period of
      preincubation, but the preincubation is ineffective if it occurs in the presence
      of hemicholinium-3. Apparently, choline or a choline-containing compound
      accumulates in the slices during the preincubation and is then utilized for the
      enhanced synthesis of ACh in the presence of tacrine. Tacrine did not induce a
      decrease in the amount of radiolabel that had been incorporated from choline into
      acid-insoluble compounds, which suggests that the choline which is used for the
      synthesis of additional ACh does not originate from choline lipids. However,
      tacrine was found to diminish the efflux of choline from prisms which had been
      preincubated with an increased concentration of choline in the medium, and from
      prisms incubated in the presence of hemicholinium-3. It also diminished the
      efflux of radioactive choline that had accumulated in the prisms during
      preincubation with a very low concentration of tacrine, when the prisms were
      subsequently incubated with 4-aminopyridine. It is proposed that the potency of
      tacrine to increase the content and synthesis of ACh in cerebrocortical prisms
      whose cholinesterases had been inhibited is due to its ability to diminish the
      efflux of endogenous choline from the nerve terminals.

PMID- 1388702
TI  - Topographic mapping of long latency "cognitive" event-related potentials (P 300):
      a double-blind, placebo-controlled study with amantadine in mild dementia.
AB  - Amantadine is generally used in the prophylaxis of infection with influenza A, in
      the treatment of Parkinson's disease and in the treatment of neuroleptic side
      effects. In this study acute effects of amantadine infusions on event-related
      potentials (ERP) were studied in 20 mildly demented patients diagnosed according
      to DSM-III-R criteria. Each patient was treated, in randomized order, with 0.2 g
      amantadine-sulfate in 500 ml NaCl and 500 ml NaCl placebo, i.v. over one hour
      with an interval of two weeks in-between. ERPs were investigated in an auditory
      odd-ball paradigm before as well as 5 hours after the infusion. In addition to 17
      EEG records, vertical and horizontal EOGs were recorded. After EOG-minimization
      and visual artifact rejection the peak latencies of the spatial average were
      determined by an automatic procedure. There was no effect of amantadine on ERP
      latencies. N1 of the non-target showed a trend towards amplitude augmentation, P2
      amplitude was reduced. As compared to placebo, P300 amplitude of targets was
      significantly augmented by 3.1 microV (30% of pre-treatment value), confirming
      the hypothesis that amantadine may influence the P 300 amplitude in the sense of
      an improved availability of cognitive processing resources.

PMID- 1388703
TI  - Brain and cerebrospinal fluid cholinesterases in Alzheimer's disease, Parkinson's
      disease and aging. A critical review of clinical and experimental studies.
AB  - Acetylcholinesterase (AChE), an enzyme responsible for the break-down of
      acetylcholine, is found both in cholinergic and non-cholinergic neurons in the
      central nervous system. In addition to its role in the catabolism of
      acetylcholine, AChE have other functions in brain, e.g. in the processing of
      peptides and proteins, and in the modulation of dopaminergic neurons in the brain
      stem. Several clinical and experimental studies have investigated AChE in brain
      and cerebrospinal fluid (CSF) in aging and dementia. The results suggest that
      brain AChE and its molecular forms show interesting changes in dementia and
      aging. However, CSF-AChE activity is not a very reliable or sensitive marker of
      the integrity and function of cholinergic neurons in the basal forebrain complex.
      Additional work is needed to clarify the role of AChE abnormality in the
      formation of pathology changes in patients with Alzheimer's disease.

PMID- 1388704
TI  - A critical review of the toxicology of glutaraldehyde.
AB  - Glutaraldehyde, a low molecular weight aldehyde, has been investigated for
      toxicity in humans and animals. Examination of this dialdehyde was indicated from
      previous studies with other aldehydes in which carcinogenicity of formaldehyde
      and toxicity of acetaldehyde and malonaldehyde have been disclosed. Information
      gaps concerning the actions of glutaraldehyde have been identified in this review
      and recommendations are suggested for additional short- and long-term studies. In
      particular, information regarding irritation of the respiratory tract, potential
      neurotoxicity, and developmental effects would assist in a complete hazard
      evaluation of glutaraldehyde. Further study related to disposition, metabolism,
      and reactions of glutaraldehyde may elucidate the mechanism of action.

PMID- 1388705
TI  - Toxicological principles of metal carcinogenesis with special emphasis on
      cadmium.
AB  - Metals are an important and emerging class of carcinogens. At least three metals,
      specifically nickel, chromium, and arsenic, are confirmed human carcinogens, and
      several more are suspected to have carcinogenic potential in man. Considering
      that the list of known human carcinogens of any type is very small, it becomes
      clear that metals make up a substantial portion of the list. Furthermore, many
      metals are very potent carcinogens in laboratory animals. Despite this,
      relatively little attention has been given to the topic of metal carcinogenesis.
      The reasons for this relative lack of attention are not clear but perhaps are
      fostered by a perception that, because metals are the simplest of molecules,
      their mechanism of action must also be simple. This could not be farther from the
      truth and, although no clear mechanisms have emerged in the area of metal
      carcinogenesis, it has become apparent that they are anything but simple. Metal
      carcinogens possess several unique characteristics including a remarkable target
      site specificity. Detection of the mechanism, or mechanisms, of metal
      carcinogenesis has, however, proven elusive, in part because of a wide diversity
      of metallic carcinogenic agents and the intricate nature of metal interactions in
      biologic systems. The following review explores this broad topic, with special
      emphasis on toxicological principles including dose-response relationships and
      potential mechanisms, using cadmium as an example.

PMID- 1388706
TI  - Cardiotoxicity of vasodilators and positive inotropic/vasodilating drugs in dogs:
      an overview.
AB  - Standard toxicological studies in dogs using high doses of vasodilators and
      positive inotropic/vasodilating agents give rise to a species-specific
      cardiotoxicity. The reason may be the extreme sensitivity of the dog to the
      pharmacological effects of these drugs; exaggerated pharmacodynamic effects and
      prolonged disturbance of homeostasis mechanisms often are responsible for the
      observed organ lesions. An assessment of the toxicological relevance and the risk
      for patients taking the drugs at therapeutic doses cannot be made without taking
      into account their pathomechanisms and the pathophysiological basis of the
      exceptional reaction patterns occurring in dogs. A large series of vasodilating
      and positive inotropic agents are presented, their pharmacological properties are
      described, and toxicological effects in dogs are compared. In view of the poor
      correlation between the distinct cardiac lesions induced in dogs and a lack of
      comparable toxicity in humans, it appears desirable to reassess the adequacy of
      the standard toxicological approaches for these substances.

PMID- 1388707
TI  - Primary hyperparathyroidism: pathology, flow cytometric DNA analysis, and
      surgical treatment.

PMID- 1388708
TI  - Cardiac troponin T in the diagnosis of myocardial injury.
AB  - In the last several decades serum levels of cardiac enzymes and isoenzymes have
      become the final arbiters by which myocardial damage is diagnosed or excluded.
      Because conventionally used enzymes are neither perfectly sensitive nor specific,
      there is need for a new sensitive and cardiospecific marker of myocardial damage.
      Cardiac troponin T (TnT) is a contractile protein unique to cardiac muscle and
      can be differentiated by immunologic methods from its skeletal-muscle isoform. An
      enzyme immunoassay specific for cardiac TnT is now available in a commercial kit
      for routine use. The biggest advantage of this assay is its cardiospecificity.
      TnT measurements, however, are also highly sensitive in diagnosis of myocardial
      injury and accurately discern even small amounts of myocardial necrosis. TnT
      measurements are, therefore, particularly useful in patients with borderline CK
      MB and in clinical settings in which traditional enzymes fail to diagnose
      myocardial damage efficiently because of lack of specificity--for example,
      perioperative myocardial infarction or blunt heart trauma. TnT release kinetics
      reveal characteristics of both soluble, cytoplasmic, and structurally bound
      molecules. It starts to increase a few hours after the onset of myocardial damage
      and remains increased for several days. TnT allows late diagnosis of myocardial
      infarction. The diagnostic efficiency remains at 98% until 6 d after the onset of
      infarct-related symptoms. TnT is also useful in monitoring the effectiveness of
      thrombolytic therapy in myocardial infarction patients. The ratio of peak TnT
      concentration on day 1 to TnT concentration at day 4 discriminates between
      patients with successful (greater than 1) and failed (less than or equal to 1)
      reperfusion. TnT measurements are very sensitive and specific for the early and
      late diagnosis of myocardial damage and could, therefore, provide a new criterion
      in laboratory diagnosis of the occurrence of myocardial damage.

PMID- 1388709
TI  - A critical analysis of postulated pathogenetic mechanisms in amyloidogenesis.
AB  - This review has examined several of the major thrusts in amyloid research, past
      and present. The data concerning amyloid precursor quantity, primary protein and
      gene structure, and precursor proteolysis have shown that there are
      contradictions that must be resolved before these elements can be reamalgamated
      into a unified view of amyloidogenesis. One possibility is presented in Figure 2.
      A general hypothesis of amyloid formation that accounts for the uniformity of
      fibril structure, amyloid staining properties, and the specific selection of
      precursors and their specific anatomic localization in each form of amyloid has
      yet to be proposed. Some of these questions may be answered by an analysis of
      common structural constituents in amyloid deposits. Analyzing amyloid generation
      in the context of these common elements separates amyloid research into several
      specific areas (Figure 2). The first area concerns factors that govern the
      expression of amyloid precursor protein genes, thus providing adequate quantities
      of the precursor, if such a precursor pool does not already exist. Without such a
      pool, amyloid deposition clearly cannot occur. The second area concerns
      information as to where these precursors usually bind and/or exert their normal
      function. Once determined, this information will likely indicate the site or
      sites where the particular precursor may give rise to amyloid deposits. The last
      area concerns factors at these local sites that govern the interaction of the
      precursor with basement membrane or related extracellular matrix elements that
      would define both the site and the final common pathway for amyloid deposition.

PMID- 1388710
TI  - Immunological functions and in vivo cell-cell interactions of T cells in the
      spleen.
AB  - The spleen is an important lymphoid organ, involved in immune responses against
      all types of antigen that appear in the circulation. Its complex anatomical
      organization, with distinct compartments containing specialized cell types,
      provides a microenvironment which allows different cell-cell interactions and
      determines the direction of developing immune responses. In this review we
      evaluate the vast amount of in vitro data dealing with antigen presentation, cell
      cell interactions, T and B cell activation, and the immunoregulatory role of
      cytokines, as suggested to be involved in immune responses. As a basis for
      understanding of in vivo processes, these in vitro data will be related to
      discrete phenomena of in vivo immune responses, such as antigen
      localization/trapping, cell migration patterns of immunocompetent cells, cytokine
      production, and antibody formation in the different compartments of the spleen.
      Finally, we try to bring order to the sequence of events that occur in the spleen
      after antigenic challenge by presenting an in vivo model for T cell dependent and
      T cell independent immune responses.

PMID- 1388712
TI  - Acquired immune deficiency syndrome.

PMID- 1388713
TI  - Insights into HIV infection and pathogenesis.

PMID- 1388711
TI  - Immunological functions of splenic B-lymphocytes.
AB  - The spleen is a key lymphoid organ for generating B-lymphocyte (B cell)-mediated
      humoral immunity. This review examines the key features and functions of splenic
      B cells. Splenic B cell subsets, including virgin, memory, and CD5+ B cells, are
      characterized by their phenotypic markers and functions. Structural aspects of
      the spleen, including red pulp, follicles, periarterial lymphoid sheaths (PALS),
      and germinal centers, are related to the B cells localized in these areas. The
      migratory behavior of B cells in these splenic compartments is considered in the
      context of antigen exposure, adhesion molecules, and migratory stimuli. Antigen
      specific B cells in the spleen are examined with an emphasis on their in situ
      characteristics assessed by immunocytochemical methods. This includes the
      detection of antigen-binding antibody-forming cells (AFC), idiotype-producing
      AFC, and the application of computer-aided imaging to analyze these cells.
      Interactions between splenic B cells and other cell types, such as T-lymphocytes
      (T cells) and antigen-processing/presenting cells like macrophages and dendritic
      cells, are briefly examined. Cytokines that influence splenic B cells are
      reviewed. Interactions between B cells and the neuroendocrine system are
      discussed briefly. The functions of splenic B cells are considered. Antibody
      production, cytokine synthesis, and potential immunoregulatory activities are
      considered.

PMID- 1388714
TI  - Morphogenesis of human immunodeficiency virus type 1.
AB  - Human immunodeficiency virus (HIV) has been implicated as the etiologic agent of
      acquired immunodeficiency syndrome and is a member of the sub-family Lentivirinae
      within the family Retroviridae. HIV type 1 (HIV-1) contains three major genes,
      gag, pol and env, which code for (1) core proteins, (2) a protease, reverse
      transcriptase and integrase, and (3) envelope glycoproteins, respectively. The
      core proteins p17, p24 and p15 are derived from gag precursor, p55, by
      endoproteolytic cleavage. The two nucleic-acid-binding proteins p7 and p9 are
      synthesized from p15 by proteolytic cleavage. These two structural proteins are
      apparently needed for the ribonucleoprotein-core formation. The envelope
      glycoproteins gp120 and gp41 (gp120-gp41 complex) are also generated by cleavage
      env precursors, gp160. The assembly of HIV-1 particles, like other retroviruses,
      appears to involve the association of the env precursor gp160 with the gag
      proteins. There are several factors which influence the assembly and budding
      process of HIV-1. In this article, we describe important events in HIV-1
      morphogenesis and factors which influence this aspect of the HIV-1 life cycle.

PMID- 1388715
TI  - Immunological characteristics of the putative CD4-binding site of the HIV-1
      envelope protein.
AB  - As an extension of previous studies demonstrating the immunosuppressive
      properties of gp120, we have analyzed the immunological characteristics of gp120
      peptides, derived principally from its putative CD4-binding site. Our studies
      indicate that peptides derived from this region do not stimulate proliferation of
      lymphocytes from HIV-seropositive donors with relatively normal numbers of CD4+
      lymphocytes. No significant proliferation was observed in response to various
      concentrations of peptide, even in the presence of interleukin-2 (IL-2).
      Significant proliferation of these lymphocytes was observed in response to two
      recall antigens, cytomegalovirus (CMV) and tetanus toxoid (TT), and these
      responses were augmented by IL-2. Peripheral blood mononuclear cells from HIV
      seronegative donors were cultured in the presence of TT and CMV and the peptides
      derived from gp120. Proliferation in the presence of these recall antigens was
      inhibited by these peptides in a dose-dependent manner. These studies demonstrate
      that at high concentrations, peptides from the putative CD4-binding site can
      inhibit proliferation of lymphocytes from normal donors in response to a recall
      antigen. The apparent immunosuppressive properties of this region highlight the
      pathogenic role played by HIV-1 envelope protein interactions with host cells.

PMID- 1388716
TI  - Regulated expression of human immunodeficiency virus type 1 in human glial cells:
      induction of dormant virus.
AB  - Human neural cells are susceptible to infection with human immunodeficiency virus
      type 1 (HIV-1) in vitro; however, virus replication in these cells is strongly
      restricted. To understand the mechanism of this restriction, we examined the
      regulation of HIV-1 expression in glial cell cultures expressing high levels of
      HIV-1 after transfection of infectious viral DNA and selection. In all cases,
      high HIV-1 expression declined to low basal levels within 4-8 weeks of
      cultivation. The decrease in HIV-1 protein production wa paralleled by the
      decline in the relative levels of the 9.2-, 4.3- and 1.8-kilobase HIV-1
      transcripts, but not by significant loss of HIV-1 DNA. Analysis of one long-term
      cell culture revealed 5 full-length unrearranged HIV-1 DNA copies per cell, but
      no viral transcripts on Northern blots, and minimal production of infectious
      virus. HIV-1 replication in these cells was markedly augmented by treatment with
      sodium butyrate (Na But) and to a lesser extent by 5-azacytidine, dibutyryl AMP
      and human herpes virus type 6. The virus induced by Na But was infectious.
      Transient expression assays revealed that Na But was more effective than phorbol
      myristate acetate in increasing the HIV-1 promoter activity in glial cells. Thus,
      one phase where glial cells can limit HIV infection is the expression of viral
      RNA from stable HIV provirus. However, such provirus remains responsive to
      inductive signals and may be activated to produce infectious HIV.

PMID- 1388717
TI  - Synthetic cyclodextrin derivatives inhibit HIV infection in vitro.
AB  - The AIDS pandemic has stimulated the search for safe potent antiviral agents. To
      date, only AZT has been approved as a therapeutic agent for the treatment of HIV
      infection. It is likely that a large number of antiviral compounds would be
      necessary to control a life-long infection. We have utilized the rigid structure
      of the cyclodextrin molecule to determine the minimal components necessary for
      anti-HIV activity. Utilizing this targeted approach to drug design, we
      demonstrate the antiviral effects of candidate compounds from the family of
      cyclodextrins. We report that polysulfated cyclodextrins mediate significant anti
      HIV effects which include blocking infectivity and syncytia formation mediated by
      the HIV viruses. Several other substituted forms of cyclodextrins did not mediate
      significant antiviral effects. Further results demonstrate that the polysulfated
      cyclodextrins mediated no specific antiviral effects against already infected
      human cells. These results demonstrate that the antiviral activities of this
      class of compounds are centered around early events in the viral life cycle.
      These in vitro results suggest that such molecules may be of importance in
      antiretroviral therapeutic regimes.

PMID- 1388718
TI  - Human immunodeficiency virus type 1 tropism for human macrophages.
AB  - Human immunodeficiency virus (HIV) infects cells of the monocyte/macrophage
      lineage in addition to lymphocytes, and infection of these cells may be
      responsible for viral persistence and dissemination, encephalopathy of the
      acquired immunodeficiency syndrome and other sequelae of HIV infection. We have
      developed an in vitro model utilizing peripheral-blood monocyte-derived
      macrophages to study HIV-1 infection of macrophages. HIV-1 isolates vary greatly
      in their ability to infect and replicate in macrophages, from highly restricted
      to highly productive infection. Productively infected macrophages undergo
      syncytium formation but remain viable in culture and support sustained levels of
      virus production for prolonged periods. Transformed monocytoid and lymphoid cell
      lines, however, show very different patterns of permissiveness for HIV-1 strains
      and do not reflect their corresponding primary cell types in studies of host cell
      tropism. Studies on viral entry show that the CD4 molecule, known to be the HIV
      receptor on lymphoid cells, is expressed at low levels on the surface of
      macrophages as well, where it functions as the receptor for viral entry.
      Therefore, differential host cell tropism does not result from the use of an
      alternative macrophage-specific receptor instead of CD4.

PMID- 1388719
TI  - Regulation of HIV-1 gene expression by cellular transcription factors.
AB  - The human CD4+ T lymphocytes in the peripheral blood represent a major target for
      HIV-1 infection in vivo. In the quiescent state T lymphocytes are nonpermissive
      for the propagation of HIV-1. Antigenic or mitogenic stimulation of T lymphocytes
      triggers a cascade of biochemical events that lead to cellular proliferation and
      activation of transcription and replication of HIV-1. Transcription of HIV-1
      provirus in infected T cells is regulated by the interaction of both viral
      proteins and cellular transcription factors with the viral long terminal repeat
      (LTR) sequences. HIV-1 LTR has been shown to contain recognition sequences for
      many cellular transcription factors. These include both positive and negative
      regulatory factors. Interplay of cellular proteins involve both the upstream and
      downstream regions of the viral LTR. Our full understanding of the
      transcriptional regulation of HIV-1 provirus will require isolation and
      characterization of each of these cellular factors which bind to the HIV-1 LTR.
      Mutational analyses of HIV-1 LTR indicate that not all these various cellular
      factors are absolutely essential for the regulation of LTR-mediated viral gene
      expression, but their presence or absence may determine the course of HIV-1
      replication in the infected cells. A balance between the inhibitory host
      transcription factors and the stimulatory cellular and/or viral protein factors
      possibly determine the final consequence of HIV-1 replication and pathogenesis.

PMID- 1388720
TI  - Viral determinants of cellular tropism.
AB  - Cells of mononuclear phagocyte lineage are the predominant cell type producing
      human immunodeficiency virus type 1 (HIV-1) in extravascular tissues; HIV-1
      infection of mononuclear phagocytes may be directly related to primary disease
      manifestations and also appears to contribute to the immune deficiency of AIDS.
      Whereas peripheral blood lymphocytes are permissive for nearly all strains of HIV
      1, only some HIV-1 strains replicate efficiently in mononuclear phagocytes.
      Recombinant virus strains have been used to identify a 157-amino acid region of
      gp120 that can confer macrophage tropism. This region is distinct from the
      principal CD4 binding domain of gp120 and includes the major type-specific
      neutralizing epitope located in the third hypervariable domain, V3. Quantitative
      assay of HIV-1-specific DNA by polymerase chain reaction early after infection
      suggests that HIV-1 strain differences in macrophage tropism are determined at
      the level of entry. These studies suggest that target cell interactions with
      gp120 in addition to or in conjunction with the CD4 binding domain are necessary
      for efficient entry into mononuclear phagocytes.

PMID- 1388722
TI  - The role of monocyte/macrophages and cytokines in the pathogenesis of HIV
      infection.
AB  - The monocyte/macrophage system, which is characterized by a high degree of
      heterogeneity, is a target of the human immunodeficiency virus (HIV) in vitro as
      well as in vivo. Both bone-marrow-derived precursor elements and circulating
      monocytes are infectable in vitro and have also been found infected in
      seropositive individuals. However, terminally differentiated macrophages are the
      most commonly infected cells found in vivo in addition to the CD4+ T lymphocytes.
      Several immunoregulatory cytokines have been shown to either up-regulate or
      suppress virus replication/expression in vitro in cells belonging to the
      monocyte/macrophage lineage by affecting both transcriptional as well as
      posttranscriptional events. The observation that elevated levels of several of
      these cytokines are present in HIV-infected individuals suggests that they may
      play an important role as regulators of virus expression in vivo.

PMID- 1388721
TI  - Analysis of the viral determinants underlying replication kinetics and cellular
      tropism of human immunodeficiency virus.
AB  - Human immunodeficiency viruses (HIVs) isolated from infected individuals show
      genetic and biological diversity. To delineate the genetic determinants
      underlying specific biological characteristics such as rate of replication and
      cellular tropism, generation of hybrid HIV using viruses which exhibit distinct
      biological feature is essential. We have used three different infectious HIV
      proviral DNAs, designated pZ6, pHXB2 and pARV, derived from HIVZr6, HIVHTLV-IIIB
      and HIVSF-2 strains, respectively, to construct hybrid HIV. Proviral DNAs
      differed in their ability to direct the synthesis of viral particles upon
      transfection into cells and the viruses derived from the molecular clones
      exhibited different cellular tropism. Three different methods were utilized to
      generate hybrid HIV, including construction of hybrid proviral DNA using
      molecular techniques, intracellular ligation of viral DNA fragments and the
      homologous recombination approach. The chimeric proviral DNAs with exchanges
      involving only the long terminal repeat (LTR) region indicated that LTR does not
      exert influence on the overall level of virus production despite extensive
      differences in the U3 region of the LTR. Regarding the cellular tropism of HIV,
      the virus derived from pHXB2 productively infected CEMx174 cells. On the other
      hand, pARV-derived virus did not show productive infection of CEMx174 cells. The
      hybrid HIV containing the 3'-end of the genome from pARV and the 5'-end of the
      genome from pHXB2 was effective in infecting CEMx174 cells. However, the converse
      hybrid containing the 5'-pARV and the 3'-pHXB2 was not effective in infecting
      CEMx174 cells. These results suggest that differences in the genes outside of env
      and nef may play a role in the ability of virus to infect a certain cell type.

PMID- 1388723
TI  - Evolutionary origins of the transforming growth factor-beta gene family.
AB  - A molecular phylogeny for the transforming growth factor-beta (TGF-beta) gene
      family based on a comparison of nucleotide sequences is proposed. A phylogenetic
      tree constructed from these sequences shows that the family evolved from a common
      ancestral gene that came into existence at about the time of arthropod and
      chordate divergence. This model suggests that the present day TGF-beta gene
      family consists of four members: TGF-beta 1 (= TGF-beta 4), TGF-beta 2, TGF-beta
      3, and TGF-beta 5. The molecular phylogeny and Southern hybridization data also
      suggest that the proteins for mammalian TGF-beta 1 and chicken TGF-beta 4 are the
      products of homologous rather than duplicated genes. If the gene duplication
      event that produced the ancestral gene for TGF-beta 1 occurred before the
      divergence of birds and mammals, then sufficient time would have elapsed to
      generate these quite distinct avian and mammalian TGF-beta 1 proteins. Therefore,
      the TGF-beta family contains four distinct proteins, TGF-beta 1, 2, 3, and 5.

PMID- 1388724
TI  - cDNA cloning and sequence analysis of beta ig-h3, a novel gene induced in a human
      adenocarcinoma cell line after treatment with transforming growth factor-beta.
AB  - Transforming growth factor-beta (TGF-beta) is capable of affecting the
      proliferation of many cell types. To identify novel genes whose protein products
      may mediate cellular responses to this factor, a cDNA library was made from mRNA
      isolated from a human lung adenocarcinoma cell line (A549) that had been treated
      for 3 days with TGF-beta. The library was screened by differential hybridization
      and a cDNA clone, beta ig-h3, was isolated. This gene was induced up to 20-fold
      in A549 cells after 2 days of treatment with TGF-beta 1. It was also induced in
      several other cell lines, including PC-3 and H2981. DNA sequence analysis of beta
      ig-h3 indicated that it encoded a novel protein, beta IG-H3, of 683 amino acids,
      which contained an amino-terminal secretory sequence and a carboxy-terminal Arg
      Gly-Asp (RGD) sequence that can serve as a ligand recognition site for several
      integrins. beta IG-H3 also contained short amino acid regions homologous to
      similar regions in Drosophila fasciclin-I and four homologous internal domains,
      which can be folded into a potential bivalent structure and could act as a bridge
      between cells expressing the appropriate ligand. beta ig-h3 RNA was detected in
      several cell lines and tissues. COS cells transfected with plasmids encoding beta
      IG-H3 secreted a major 68-kD protein that was detected by immunoblotting using
      antipeptide antibodies. Since beta ig-h3 is induced in several cell lines whose
      proliferation is affected by TGF-beta 1, it may be involved in mediating some of
      the signals of this multifunctional growth modulator.

PMID- 1388726
TI  - The retinoblastoma protein region required for interaction with the E2F
      transcription factor includes the T/E1A binding and carboxy-terminal sequences.
AB  - Recent experiments in understanding the mechanism of the retinoblastoma protein
      (RB) function have revealed the existence of several cellular proteins that are
      complexed with RB. One of these cellular proteins is the E2F transcription
      factor, which was originally identified due to its inducibility by E1A during an
      adenovirus infection. The E2F recognition sequence is found in the promoters of
      several cellular genes involved in growth control, including several oncogenes.
      In this report, we provide evidence that the interaction of E2F and RB is
      mediated through a region on RB where viral oncogenes such as SV40 T antigen and
      adenovirus E1A bind and where tumorigenic mutations also cluster. Additional
      carboxy-terminal sequences are also required for the interaction with E2F. These
      observations provide evidence for a direct connection between tumor suppressor
      function and the gene expression program leading to cellular growth regulation.

PMID- 1388725
TI  - Molecular cloning and characterization of a novel Rel/NF-kappa B family member
      displaying structural and functional homology to NF-kappa B p50/p105.
AB  - The NF-kappa B transcription factor has been implicated in the inducible
      expression of many genes, including inflammatory, immune, and acute-phase
      response genes. NF-kappa B consists of two subunits, 50K and 65K polypeptides.
      The genes encoding p50 and p65 have sequence similarities with the c-rel proto
      oncogene and the Drosophila maternal effect gene dorsal. We describe the cloning
      and characterization of a novel rel-related gene encoding a 98K product that
      shares extensive homology with the p105 precursor of the NF-kappa B p50 protein,
      containing both a Rel homology and SWI6/ankyrin repeat domain. We demonstrate
      that p98 is proteolytically processed in vivo to generate a 55K polypeptide,
      which binds to kappa B sites. p55 is capable of forming heterocomplexes with
      other Rel/NF-kappa B family members, which can bind to kappa B motifs in vitro,
      and stimulate transcription of reporter genes containing these cis-elements in
      vivo. The identification of a homolog for NF-kappa B p50/p105, termed p55/p98,
      gives further support to the idea that NF-kappa B is a collection of structurally
      related complexes of which contribute to the pleiotropic regulatory processes
      originally assigned to NF-kappa B.

PMID- 1388727
TI  - Insulin-producing cells contain a cell-specific repressor activity that functions
      through multiple E-box sequences.
AB  - The cis-acting DNA element known as the E box (consensus sequence CAxxTG) plays
      an important role in the transcription of a number of cell-specifically expressed
      genes. The rat insulin I gene, for example, contains two such sequences (IEB1 and
      IEB2) that are recognized specifically by a characteristic beta cell nuclear
      factor insulin enhancer factor 1 (IEF1). To define the role of these elements
      better, we tested for cooperative interactions between the IEB sequences.
      Transfection experiments were performed with a series of plasmids containing the
      elements separated by different distances. Transcriptional activity in vivo is
      only modestly affected (less than two-fold) when the distances between the IEB
      elements are changed by a half-integral number of double-helical turns.
      Surprisingly, plasmids bearing four and six copies of the IEB motif showed
      sharply reduced activity as compared to those with two copies. In vitro DNA
      binding studies revealed that this effect was not due to inability of IEF1 to
      bind to multiple copies of IEB. Moreover, multiple copies of the IEB sequence
      were able to inhibit activity of a cis-linked Moloney sarcoma virus (MSV) or
      insulin enhancer upon transfection to beta cells but not to other cell types. The
      above data are consistent with the view that beta cells contain a cell-specific
      repressor molecule capable of binding to multiple copies of IEB and thereby
      inhibiting transcription. This interpretation was further strengthened by in vivo
      competition and trans-activation experiments. The beta-cell-specific repressor
      activity identified by these studies may play an important role in mediating gene
      expression in insulin-producing cells, perhaps by regulating the access of helix
      loop-helix transcription factors to E-box sequence elements.

PMID- 1388728
TI  - The down-regulation of albumin transcription during regeneration is due to the
      loss of HNF-1 and the D-site transcription factors.
AB  - Liver regeneration has served as an important in vivo model for studying the
      control of differentiation. The molecular mechanisms responsible for the negative
      regulation of the albumin promoter during regeneration have not been examined
      previously. Changes in the proteins interacting with the albumin promoter were
      characterized using nuclear extracts prepared from the livers of rats undergoing
      chemically induced regeneration. Reduction in the activities of both hepatocyte
      nuclear factor-1 (HNF-1) and factors binding to the D site are responsible for
      the loss of albumin transcription during regeneration. No evidence for the
      involvement of a transcriptional repressor in this process was found.

PMID- 1388730
TI  - Isolation of a yeast gene encoding a protein homologous to the human Tat-binding
      protein TBP-1.
AB  - We have cloned a putative yeast homolog of the gene encoding the human Tat
      binding protein, TBP-1. The gene termed TBPY encodes a 45,243-dalton protein
      displaying a heptad repeat of hydrophobic amino acids reminiscent of a leucine
      zipper. Secondary structure predictions suggest the possibility of formation of
      an amphipathic helix that could further be organized into a coiled-coil.
      Additionally, the protein product of TBPY shows amino acid signatures
      characteristic of a large family of RNA and DNA helicases. We propose that the
      hydrophobic region of yTBP-1 participates in self-dimerization or
      heterodimerization.

PMID- 1388729
TI  - A pink bacterium as a reporter system signaling expression of a recombinant
      protein.
AB  - We describe a set of expression vectors, pEX-PINK/0-3, for high-level production
      of (un)fused target proteins. The vectors incorporate a 'pink' reporter element,
      which signals in vivo the expression status of a target gene. A target sequence
      is cloned between the lambda PL promoter and the downstream mammalian cytochrome
      b5 gene. Thermo-induction drives transcription of a dicistronic mRNA from which
      the target protein and cytochrome b5 are independently and concurrently
      synthesized. Positive expression is indicated by visual transformation of
      bacteria from a grey/translucent to a bright pink color derived from tandemly
      expressed holocytochrome b5. The signal can be monitored in vivo
      spectrophotometrically.

PMID- 1388731
TI  - Two mRNAs are transcribed from the human gene for choline acetyltransferase.
AB  - The product of the choline acetyltransferase (ChAT) gene is the enzyme that
      synthesizes the neurotransmitter acetylcholine. A 14.4-kb portion of the human
      ChAT gene contains 7 exons, which are estimated to comprise approximately one
      third of the human protein coding sequence by comparison with porcine ChAT mRNA.
      Two of the exons were used to identify polyadenylated human ChAT gene transcripts
      on Northern blots. An exon with 84% identity to the region of porcine ChAT mRNA
      that codes for the amino terminus of the corresponding protein detected 6,000-
      and 2,300-nucleotide mRNAs in RNA isolated from human CHP134 neuroblastoma cells.
      Only the 2,300-nucleotide mRNA was detected by a second probe containing an exon
      with 96% identity to porcine ChAT mRNA in the domain that encodes amino acids 204
      263 of the predicted porcine ChAT protein. Further evidence that two species of
      human mRNA are produced from the human ChAT gene was obtained from nuclease
      protection assays using an antisense RNA probe prepared from a human ChAT cDNA
      clone. Total RNA isolated from either CHP134 cells or adult human nucleus basalis
      protected 525- and 400-nucleotide fragments of this probe, confirming the
      presence of two species of RNA that differ by the inclusion of an internal exon.
      cDNA clones of each of these transcripts have been isolated. Their sequences
      suggest that the 2,300-nucleotide mRNA encodes enzymatically active human ChAT,
      while translation of the 6,000-nucleotide mRNA would be terminated prematurely by
      a shift in the reading frame. These results indicate that a complex pattern of
      transcription produces two mRNAs with different coding potentials from the human
      ChAT gene.

PMID- 1388732
TI  - The isolation of evolutionarily conserved Eag I end-clones from mouse chromosome
      17 using cloned DNA.
AB  - To isolate DNA markers from mouse chromosome 17, a genomic phage library was
      constructed from the mouse-hamster CMGT cell hybrid RcE-B52. This hybrid contains
      a chromosomal fragment from the distal end/flanking region of the t complex on
      mouse chromosome 17. Recombinants of mouse origin were identified by using a
      panel of mouse-specific repetitive sequences as a probe. A total of 1,500 mouse
      phage recombinants were isolated. These were found to represent 250-300
      individual recombinants, comprising about 4 Mbp of cloned mouse DNA. The pooled
      mouse recombinant phages were used to construct an Eag I end-library. This was
      achieved by the specific insertion of a marker plasmid in Eag I recognition sites
      when present in the mouse inserts of the recombinant phages. The Eag I end
      fragments were subsequently subcloned using a simple procedure taking advantage
      of the inserted plasmid. A total of 56 individual Eag I end-fragments were
      identified. These were found to contain recognition sites for rare cutting
      enzymes at high frequency. A large proportion (73%) were found to be
      evolutionarily conserved in human DNA. Furthermore, a significant fraction of
      these fragments, two of six tested, appears to detect specific cDNAs in a 8.5-day
      mouse embryo cDNA library.

PMID- 1388733
TI  - Immunoelectron microscopic detection of the hepatitis B virus major surface
      protein in dilated perinuclear membranes of yeast cells.
AB  - The major surface protein of hepatitis B virus produced in Saccharomyces
      cerevisiae can be recovered from cell lysates in the form of 22-mm lipoprotein
      particles. Immunoelectron microscopy was applied to investigate site and time of
      particle assembly. Thin sections of yeast cells revealed that production of the S
      protein provoked a dilation of the endoplasmic reticulum. Dilated areas were
      specifically labeled with a polyclonal antibody raised against glutaraldehyde
      treated yeast-derived HBsAg particles. In contrast to previous postulates of
      particle formation during cell lysis and extract preparation, these results
      suggest that particle formation in yeast occurs in the endoplasmic reticulum and
      that transport of particles along the secretion pathway is blocked.

PMID- 1388734
TI  - Direct PCR sequencing of dystrophin polymorphic CACA alleles after purification
      to remove shadow bands.
AB  - A method is described that allows the sequencing of polymerase chain reaction
      (PCR) products containing CACA repeats. The method was tested using a DNA
      polymorphism that exists at the 3' end of the dystrophin gene. This polymorphism
      consists of a variation in the length of a CACA dinucleotide repeat. Four alleles
      from a total of 16 individuals were sequenced at this locus after the DNA
      sequence had been amplified by the PCR. Five examples of each of the common
      alleles were sequenced. For each allele all five sequences were the same. The
      only example of a rare allele was also sequenced. The PCR products of DNA
      sequences containing dinucleotide repeats consist of a number of bands differing
      by 2 bp below the most intense main band. Previously, direct sequencing of the
      PCR products lead to ambiguities and smearing at and above the CACA repeat. In
      this paper, the main PCR band was cut out of a sequencing gel and directly
      sequenced to give a clear DNA sequence. Our results indicate that for a
      particular allele, all individuals had exactly the same DNA sequence. This
      implies that with the appropriate choice of oligonucleotide primers,
      polymorphisms could be detected without electrophoresis.

PMID- 1388735
TI  - [Levels of competence; an imposed question].

PMID- 1388736
TI  - ['To be open about dying is the hardest'. Interview by Toine de Graaf].

PMID- 1388739
TI  - [The RIVM (Federal Institute for Public Health and Environmental Hygiene), or:
      research serving man and environment. Forecasting as focal task].

PMID- 1388738
TI  - [Huize Vogelsangh in Hilversum--not dying in the street].

PMID- 1388737
TI  - [To die at home is possible].

PMID- 1388740
TI  - [WOI-NVGz (Workgroup of Organizations of Parents and Boarding Schools-Dutch
      Organization for Care of the Handicapped), 15 years of mutual involvement].

PMID- 1388741
TI  - [Brain infarct--1. Symptoms, causes and treatment].

PMID- 1388742
TI  - [Brain infarct--2. Diagnosis and treatment].

PMID- 1388743
TI  - [Environment and health care. 'Make sure you're well informed before giving
      advice to anyone'. Interview by Toine de Graaf].

PMID- 1388745
TI  - [Slingeland Hospital Doetinchem--more than expediency].

PMID- 1388744
TI  - [Patience and solidarity--Werner and Le Grand one year after the date].

PMID- 1388746
TI  - [Dutch entry wins Hartmann Nursing Prize '92].

PMID- 1388747
TI  - [Ordinary dealing with extraordinary people. No utopia but reality].

PMID- 1388748
TI  - [Children's quality of life does not always agree with medical competence.
      Centennial NVK (Dutch Society for Pediatrics) is thought-provoking].

PMID- 1388749
TI  - [Nutritional management in colorectal tumors].

PMID- 1388750
TI  - Cytochrome P-455 nm complex formation in the metabolism of phenylalkylamines.
      XIII. Enzyme interactions with a series of beta-alkyl-substituted 2
      phenylethanamines and corresponding N-hydroxylamines.
AB  - The formation of Metabolic Intermediate (MI) complexes from a series of beta
      alkylsubstituted 2-phenylethanamines and corresponding N-hydroxylamines is
      investigated during NADPH-dependent metabolism in liver microsomes from
      phenobarbital pretreated rats. The beta-alkyl substituents are methyl, dimethyl,
      ethyl, di-ethyl, n-propyl, di-n-propyl and i-propyl groups. The amines are
      synthesized by LiAlH4-reduction of the corresponding nitriles, which are prepared
      through alkylation of the enolate anion of phenylacetonitrile. The hydroxylamines
      are prepared either by oxidation of the corresponding benzylimines with m
      chloroperbenzoic acid and subsequent hydrolysis of the initially formed 3
      phenyloxaziridines, or by H2O2-mediated oxidation of the corresponding amines in
      the presence of catalytic amounts of sodium tungstate, followed by reduction with
      cyanoborohydride. The amines are found to be completely devoid of complexing
      activity, while the hydroxylamines form the MI complex at high rates. Complex
      formation from these substrates thus parallels the known behaviour of 2
      phenylethanamine and its corresponding N-hydroxylamine. Since N-oxygenation is
      known to be a prerequisite for MI complex formation from amines our results
      suggest that the beta-alkylated 2-phenylethanamines are metabolized exclusively
      through other pathways. In accordance with this hypothesis, capillary GC-analysis
      of the incubation mixture of 2-phenylpropanamine shows no formation of N
      hydroxylated metabolites; only 2-phenylpropanol, a metabolite formed through the
      deamination pathway, is found.

PMID- 1388751
TI  - Topical administration of drugs.

PMID- 1388752
TI  - Barrier properties of the skin.

PMID- 1388753
TI  - Basic principles of transport from topical preparations.

PMID- 1388754
TI  - Skin barrier function and the mechanism(s) of percutaneous penetration.

PMID- 1388755
TI  - Properties of suction de-epithelialized skin relative to drug delivery.

PMID- 1388758
TI  - How to optimize drug penetration through the skin.

PMID- 1388757
TI  - Formulation aspects on dermatological preparations and transdermal drug delivery
      systems.

PMID- 1388759
TI  - Pharmacokinetic modelling of penetration through the skin.

PMID- 1388760
TI  - Predicting percutaneous absorption.

PMID- 1388756
TI  - Skin absorption of drugs.

PMID- 1388762
TI  - Reconstructed skin as a tool in the development of topical drugs for dermatology.

PMID- 1388761
TI  - Local anaesthetics--comparison of in vitro and in vivo data.

PMID- 1388763
TI  - Fluorescence spectroscopic evaluation of stratum corneum lipids--implications for
      permeation enhancement.

PMID- 1388764
TI  - Use of chemical penetration enhancers in transdermal drug delivery--possibilities
      and difficulties.

PMID- 1388765
TI  - Topical drugs and cosmetics.

PMID- 1388766
TI  - Contact sensitivity to corticosteroids.

PMID- 1388767
TI  - Cutaneous adverse reactions to transdermal delivery systems--mechanisms and
      prevention.

PMID- 1388768
TI  - Diagnostic tests of contact sensitivity.

PMID- 1388769
TI  - Skin irritancy evaluated by laser Doppler flowmetry.

PMID- 1388770
TI  - Predictive animal sensitization assays.

PMID- 1388771
TI  - Visions of the future for transdermal drug delivery.

PMID- 1388772
TI  - A quantitative structure-activity relationship for some dopamine D2 antagonists
      of benzamide type.
AB  - A quantitative structure-activity relationship (QSAR) for some 6
      methoxybenzamides having 1-ethyl-2-pyrrolidinylmethyl side chains with respect to
      the inhibition of [3H]spiperone binding is established using the PLS method. An
      experimental design approach to select the training set compounds is
      demonstrated. The established relationship between structure and in vitro
      activity indicates the dominating influence of the substituents in the 3-position
      as well as the importance of (S)-configuration in the side chain. A methoxy
      substituent in the 5-position is also beneficiary for high activity. Both
      salicylamides and non-salicylamides could be accommodated in the analysis, which
      supports the notion of a common binding site in the receptor.

PMID- 1388773
TI  - Investigation of the applicability of a tensile testing machine for measuring
      mucoadhesive strength.
AB  - The applicability of a tensile testing machine (M30K, JJ Lloyd Instruments Ltd,
      GB) is investigated for measuring mucoadhesive strengths. A sample of an aqueous
      dispersion of a polymer with expected mucoadhesive properties is placed between
      two homemade discs of polyoxymethylene. The upper disc is mounted on a movable
      part of the machine while the lower disc is fixed on the stationary frame. A
      tensile force is submitted and the maximum detachment force at fracture and the
      adhesion work are estimated from the force displacement curve recorded. In some
      experiments, native mucous tissue of the large intestine of pigs was glued to the
      upper disc. Four polymers polycarbophil (Carbopol EX-55), carboxypolymethylene
      (Carbopol 934P), hydroxypropylmethylcellulose (Methocel K4M), and sodium
      alginate, are used in five different concentrations. At least three measurements
      are made of each polymer and concentration. Viscosity and osmolality are
      determined. By standardizing the time of sample equilibration and the run rate
      before measurement, it is possible to get good reproducibility of the tensile
      values. Based on the maximum nominal breaking force and the work consumed, it is
      concluded that the tensile strength is dependent both on the concentration and
      the type of polymer. The conclusions are the same independent of whether mucous
      pig tissue is used, or not. The same rank order in adhesive properties of the
      polymers is achieved as from using modified surface tensiometers.

PMID- 1388774
TI  - Bioassay-guided isolation of serotonin from fruits of Solanum tuberosum L.
AB  - An ethanol extract of the fruits of Solanum tuberosum was partitioned between
      water and petroleum ether. The aqueous fraction had contractive effect on the
      isolated guinea-pig ileum. Chromatography of this fraction on Sephadex LH-20 and
      silica gel was monitored by the guinea-pig ileum test and resulted in isolation
      of serotonin. HPLC analysis of the content of serotonin in fruits, leaves and
      tubers of the plant, showed that the fruits and leaves contained 7.5 micrograms
      and 2 micrograms, respectively, of serotonin/g fresh weight. In agreement with
      previous observations, no serotonin was detected in the tubers.

PMID- 1388775
TI  - Synthesis and antihypertensive activity of imidazo[2,1-b]-thiazoles bearing a 2,6
      dichlorophenyl group.
AB  - A number of imidazo[2,1-b]thiazoles bearing a 2,6-dichlorophenyl group as
      hydrazone or as amide were prepared and tested in rats as antihypertensive
      agents. Only compounds bearing a chlorine at position 6 were active.

PMID- 1388776
TI  - [Children and AIDS].

PMID- 1388777
TI  - [Overview of HIV infections in pediatric population].
AB  - A general overview of HIV infection/AIDS in the pediatric population, in Mexico,
      is provided. The principal categories of transmission in our country are: 45.5%
      perinatal, 44.0% following transfusion for hemophilia or for other reasons, and
      less frequently sexual transmission. In the United States and Europe, similar
      patterns are seen with perinatal transmission being the most important route, at
      higher percentages than ours. The number of cases of HIV infection in children
      continues to grow worldwide, primarily reflecting the problem in the adult
      population.

PMID- 1388778
TI  - [Central nervous system pathology in children with AIDS].
AB  - The neuropathological manifestations of AIDS in children vary widely and
      includes, among others: cerebral atrophy, basal ganglia calcification,
      corticospinal tract demyelinization, and HIV encephalomyelitis with
      multinucleated cells. The purpose of this work is to inform the postmortem CNS
      findings in 14 pediatric AIDS patients which were studied from January 1986 to
      February 1992, at the Hospital Infantil de Mexico Federico Gomez. Basal ganglia
      vascular calcification, HIV multinucleated cells, and corticospinal tract
      demyelinization, were significantly less frequent (P < 0.01) in our patients than
      those informed in the literature. Opportunistic CNS infections found in our
      patients were produced by microorganisms commonly described in adults. We think
      that these differences may be explained because the majority of our patients
      acquired the infection trough blood transfusion at an age in which the CNS is
      fully developed. The pattern of HIV transmission in our country has been changing
      recently with an increase in the number of perinatal cases. We also think that in
      the near future we will observe a change in the neuropathological findings of our
      pediatric AIDS population.

PMID- 1388779
TI  - [Neurologic manifestations in pediatric patients with AIDS].
AB  - Since the first cases of childhood AIDS were reported, the neurological
      involvement has been more frequently recognized. Several motor, intellectual and
      conductual changes as well as unexplained abnormalities have been described due
      to CNS infections. Findings have shown HIV to affect the CNS although it is
      unknown as to when the viral invasion actually occurs. This report describes the
      neurological manifestations found in pediatric patients with HIV infection at the
      Hospital Infantil de Mexico and their correlations with CT scans, EEGs, auditory
      evoked potentials, I.Q.s and postmortem findings. The medical records of 60
      symptomatic HIV infected children, stages P0 to P2, are reviewed. Neurological
      abnormalities were found in 51 patients, 20 of which (39.2%) were due to
      perinatal infection with symptoms starting, on the average at 11 months 7 days
      (from the initial contact) taking into consideration in utero exposure. Nine
      cases (17.6%) were patients infected through transfusions with symptoms appearing
      on the average at 24 months 8 days; 2 cases (3.9%) were of unknown origin. The CT
      scans, EEGs and psychometric evaluations of the HIV infected patients correlated
      well with the clinical findings.

PMID- 1388780
TI  - [AIDS in children. Experience at the National Institute of Pediatrics].
AB  - We describe retrospectively the experience with 44 cases of AIDS from January
      1987 to October 1991 at the Instituto Nacional de Pediatria, a tertiary care
      children hospital in Mexico City. All patients with 2 ELISA and a positive
      Western Blot test were included. Thirty three patients were infected perinatally
      (75%) and 11 through blood transfusion (25%). Fourty one patients belonged to the
      P2 classification of the Centers for Disease Control. Chronic diarrhea (77%),
      lymphadenopathy (75%), hepatomegaly/splenomegaly (70%) and oral candidiasis (61%)
      were the most common clinical findings. Twenty patients died (45.4%). No
      statistical relation were found between survival rate and the way of transmission
      and age at onset. Autopsy was performed in 14 patients and revealed a sharp
      decrease of lymphoid tissue at all levels with severe thymic atrophy.

PMID- 1388782
TI  - [AIDS in children. 8 years experience at La Raza Medical Center Infectology
      Hospital, Mexican Social Security Institute].
AB  - The objective for this work was to describe the transmission mechanisms and the
      clinical behavior of 60 HIV-infected pediatric patients. We studied children from
      newborn to 15 years old according to the CDC criteria. From January 1985 to
      February 1992, were evaluated 60 patients, 40 males and 20 females; 25 with
      perinatal transmission (23 transplacental and 2 breast-feeding), 22 hemophiliacs,
      12 by blood transfusion and 1 by intramuscular injection with contaminated
      needle. The disease was symptomatic in 50 patients, asymptomatic in 5 and
      indeterminate in 5 cases. Up to date, 28 children are in phase P2, 10 in P0 and
      P1, and 22 patients have died. The clinical manifestations in 50 patients were:
      altered growth and development in 50, generalized lymphadenopathy in 30, severe
      infections in 23, fever in 15, hepatosplenomegaly in 15, chronic diarrhea in 10,
      and HIV-encephalopathy in one. It is concluded what at present time perinatal
      transmission is the main mechanism.

PMID- 1388781
TI  - [Perinatal transmission of AIDS. Experience at the National Institute of
      Perinatology].
AB  - From January 1989 to February 1992, 19 pregnant women infected with human
      immunodeficiency virus (HIV) were attended at the Instituto Nacional de
      Perinatologia in Mexico City, all of them at the end of pregnancy as well as 15
      of their offspring. Sexual transmission was found in 15 patients; the initial
      classification of 16 was CDC II, only one case with AIDS, and during pregnancy 2
      cases changed their clinical status. Absolute CD4 count in 2 cases was lower 20%,
      None of 10 had positive VDRL and one case showed a positive PPD. All neonates
      were at term and eutrophics. During their first 3 months of life, 2 had an
      infectious disease and died. The serologic follow-up at the moment reports 3
      having HIV infection (20%), 3 no HIV infection and 9 in study are sero-positive.

PMID- 1388784
TI  - [Oral manifestations in HIV positive children].
AB  - Oral manifestations of HIV infection in children include oral candidiasis,
      herpetic stomatitis, oral hairy leukoplakia, parotid gland swelling, and other
      bacterial, viral and mycotic infections. The frequency and natural history of
      those disorders are not fully defined. The purpose of this work is to inform the
      oral findings in 57 HIV infected children studied at the Hospital Infantil de
      Mexico. All 57 patients presented nonspecific gingivitis; however it was not
      feasible to associate it with the HIV infection; in 28 oral candidiasis was
      observed, and in 3 cases herpetic stomatitis was documented. Oral candidiasis was
      found regardless the patient's sex, age, clinical stage, treatment, and mode of
      transmission of the HIV infection. It has been considered that oral candidiasis
      is a good marker of immunodeficiency; however, in our patients this correlation
      was not observed. Also, other HIV-associated oral manifestations were not
      observed in these cases. The severity and rapid clinical course presented by our
      patients, may explain both, the lack of correlation between candidiasis and
      immunodeficiency as well as the absence of other lesions.

PMID- 1388785
TI  - [Nephrotic syndrome associated with AIDS in children].
AB  - Several renal and renal-related disturbances have been described in patients with
      AIDS (acquired immune deficiency syndrome), in adults and children as well. These
      are mainly electrolyte and acid-base imbalance, acute renal failure and nephrotic
      syndrome. The latter is usually steroid non-responder. The renal
      histopathological lesions described more commonly are minimal change, mesangial
      hyperplasia and focal segmental glomerulosclerosis. Herein, we describe a 5 year
      old with AIDS, that developed nephrotic syndrome, characterized by edema,
      ascites, hypoalbuminemia and massive proteinuria. A percutaneous renal biopsy
      showed mesangial proliferation. She did not respond to a 6 week treatment with
      prednisone. She died with sepsis after several viral and bacterial infections.

PMID- 1388783
TI  - [Bacterial infections in children with AIDS].
AB  - The importance of bacterial infections in children with AIDS was emphasized when
      they were included within the CDC classification system for children under 13
      years of age infected with the HIV. The information available in Mexico on
      frequency, types of infections and causative agents is scarce. In this study, the
      frequency and microbiology of bacterial infections in children with AIDS seen at
      the Hospital Infantil de Mexico Federico Gomez is reported. From September 1985
      to December 1991, we found 72 HIV infected children, 6 were classified P0, 6 as
      asymptomatic (P1) and 60 as symptomatic infections (P2). From this last group, 50
      were secondarily infected with bacteria; there was a total of 129 episodes of
      bacterial infections, averaging 2.5 episodes per patient. Respiratory infections
      were the most frequent (74.41%), followed by septicemia (10.07%), skin and
      underlying tissue infections (6.96%) and urinary tract infections (6.17%).
      Infections of the CNS and deep abscesses were less frequent. Overall mortality
      rate was 76%, however only in 18 children (36%) was it directly attributed to the
      bacterial infections. Etiology was documented in 46 episodes (33.65%) of which 30
      (65.31%) were gram-negative bacteria and 16 (34.78%) were gram-positive. The best
      possible methodology must be used for the etiologic diagnosis of bacterial
      infections in children with AIDS in order to select the most appropriate
      treatment for severe or recurrent bacterial infections.

PMID- 1388786
TI  - [Coronary arteriopathy associated with cardiomyopathy in an adolescent with
      AIDS].
AB  - The purpose of this paper is to inform the case of a 15 years old male patient
      who died as a consequence of acquired immunodeficiency syndrome (AIDS)
      complications. The postmortem examination showed a coronary lesion which, to the
      best of our knowledge, has not been previously described. This vasculopathy was
      restricted to the coronary arteries; myocardial changes similar to those
      described in AIDS-associated dilated cardiomyopathy were also present. The
      coronariopathy was indistinguishable from that described in the blood vessels of
      the brain in patients with AIDS-related cerebral arteriopathy. We also reviewed
      the autopsy material from another 14 children who died of AIDS, an in none of
      them exhibited similar changes in the coronary arteries. In addition we present
      the clinical findings and some theoretical considerations regarding the
      pathogenesis of the lesions.

PMID- 1388787
TI  - [Health care worker relationship with HIV infected patients or AIDS patients].
AB  - The roll of the health care worker (HCW) providing care to HIV-infected patients
      or living with AIDS has became an important issue in the course of the epidemic,
      and has impacted the evolution of these patients. Diverse studies have shown that
      the acceptance of the HCW to care for these patients is related to the degree of
      education in regards to the subject. There is a positive correlation between
      knowledge about universal precautions and mechanisms of transmission with the
      willingness to care for HIV-infected patients. This review shows several studies
      that have been developed in order to assess the attitudes among HCW's toward HIV
      infected patients and the phenomen HIV/AIDS as public health problem. In
      addition, political issues are discussed in regards to measure protection to HCW
      as well as HIV-infected patients.

PMID- 1388788
TI  - [Medical facilities for women and children infected with HIV].
AB  - The phenomena HIV infection and acquired immunodeficiency syndrome (AIDS) among
      women and children is an important concern for underdeveloped and developing
      countries and has became a Public Health problem. The medical facilities required
      for care of these patients are special and demand a comprehensive approach and
      multidisciplinary team-work. In this way, the patients would receive adequate
      care for their needs. This review includes the antecedents of the HIV infection
      among women and children. Mechanisms of transmission, and the current model of
      medical care that exists in some developed countries. Finally, a commentary is
      made in regards to the importance of continuing medical education of the health
      term in order to confront the AIDS epidemic.

PMID- 1388789
TI  - [Do AIDS cases in adolescence really exist?].
AB  - Adolescents are a specific population group, with risk practices for the
      acquisition of sexually transmitted diseases. The Centers for Diseases Control
      consider the adolescents specific group ranging between 13-19 years and they
      reported, until September 1991 that 0.4% of global AIDS cases corresponded to
      this group. In Mexico, we did an analysis of the AIDS cases reported at AIDS
      Surveillance Committee until September 1991, and found that 1.4% of the global
      AIDS cases corresponded to adolescents. The AIDS transmission pattern in
      adolescents is different from adults and children. It is very important to
      classify adolescents as a specific group in health surveillance and to considered
      all the factors related to them for AIDS prevention strategies.

PMID- 1388790
TI  - [Repercussions of blood transmission in the epidemiology of AIDS-HIV infection in
      Mexican children].
AB  - The first case of AIDS associated with contaminated blood products occurred in a
      child; with this 2 very important situations were recognized, firstly, the
      possibility of transmitting the disease through blood products, and secondly,
      that children are not exempt from acquiring the disease. Intimately related to
      transfusions of contaminated blood products are perinatal AIDS cases. With the
      measures set forth by the Mexican Government in order to prevent the transmission
      of HIV-1 through contaminated blood product, a decrease in cases of AIDS acquired
      through transfusions in expected in the near future. Not so for cases of
      perinatal AIDS, where educational campaigns directed towards women and high risk
      groups will have to be established.

PMID- 1388791
TI  - Normal and abnormal visual development in infants and children. Papers from the
      3rd meeting of the Child Vision Research Society. Rotterdam, 12-14 June 1991.

PMID- 1388792
TI  - The spectrum of leukomalacia using cranial ultrasound.
AB  - The spectrum of leukomalacia using cranial ultrasound is discussed. Transient
      densities not evolving into cystic lesions may represent a mild degree of
      leukomalacia when persisting for at least a week. A unilateral parenchymal
      density may be due to bleeding into an ischaemic area, but can also be due to a
      venous infarction. Cystic leukomalacia can be confidently diagnosed using
      appropriate equipment and performing sequential scans. A distinction should be
      made between cysts in the periventricular white matter and cysts in the deep
      white matter, as the latter carries a higher risk for cerebral visual impairment.
      Careful ophthalmological examination of these infants will enable us to identify
      infants with cerebral visual impairment during the first few months of life,
      allowing the use of special programs aimed at promoting visual development.

PMID- 1388793
TI  - Visual acuity of low- and high-risk neonates and acuity development during the
      first year.
AB  - Binocular grating acuity of 65 neonates was measured using Teller acuity cards.
      At the time of testing, age corrected for prematurity ranged from -3 weeks to 2
      weeks. On the basis of clinical data, serial ultrasound scans and EEG recording
      newborns were divided into 4 subgroups: fullterm low-risk (FLR, n = 22); preterm
      low-risk (PLR, n = 20); preterm medium-risk (PMR, n = 9) and preterm high-risk
      (PHR, n = 14). Mean visual acuity of PLR infants (0.86 cy/deg; S.D. 0.34 oct) was
      not significantly different from that of FLR newborns (0.80 cy/deg; S.D. 0.71
      oct); the lower variability of the PLR infants might possibly be caused by their
      longer postnatal experience. Within the preterm groups, mean visual acuity of PLR
      newborns was found to be significantly higher than that of PMR (0.73 cy/deg; S.D.
      0.26 oct) and PHR infants (0.73 cy/deg; S.D. 0.35 oct). This difference can not
      be explained by dissimilarities in postnatal or corrected age. Brain impairment,
      as documented by US scans and EEG recording could account for these findings.
      Longitudinal data are needed in order to substantiate these findings and
      correlate them with later neurological and neuro-imaging outcome. Preliminary
      results of an ongoing longitudinal study suggest acuity development of most, but
      not all, PHR infants, in whom a cystic-periventricular leukomalacia had been
      diagnosed, to be worse than that of low- and medium-risk infants.

PMID- 1388795
TI  - Visual segmentation of oriented textures by infants.
AB  - The infant's visual system contains orientation-sensitive mechanisms from the
      first weeks of life. Differences in texture orientation can serve as a basis for
      rapid preattentive localization and segmentation in adults. We tested whether
      infants could use their orientation-sensitive mechanisms in the same way, by
      forced-choice preferential looking, using displays of line segments oriented at
      45 degrees in a rectangular patch and 135 degrees in the surrounding region.
      Performance was compared with that for displays of similar elements with uniform
      orientation but with the patch defined by luminance contrast. Infants of 14-18
      weeks old showed consistent preference for both orientation- and contrast-defined
      patches, indicating the ability to segment the field by orientation. Infants of 8
      12 weeks performed comparably to the older infants on contrast-based segmentation
      but did not show a statistically significant preference with orientation-based
      segmentation. In a second experiment, preference was also tested for a region of
      mixed orientation versus a region of uniform orientation. The 14-18-week-olds did
      not show this preference, suggesting that their preference for the discrepant
      texture patch genuinely reflected texture segmentation and not simply the
      presence of two different orientations on one side of the display. The results
      are discussed in terms of the possible maturation of intracortical connections
      subserving texture grouping and segmentation.

PMID- 1388794
TI  - Visual field and grating acuity development in low-risk preterm infants during
      the first 2 1/2 years after term.
AB  - The effect of early visual experience on visual field size and grating acuity
      development was studied longitudinally in 36 appropriate for gestational age
      (AGA) and 26 small for gestational age (SGA) low-risk preterm infants. These were
      selected out of 194 very low birth weight (VLBW) infants (birthweight less than
      1500 g) born in 1985 and 1986. Criteria for inclusion as low-risk were the
      absence of neurological, respiratory, circulatory and alimentary problems in the
      neonatal period; no retinopathy of prematurity and no evidence of abnormality on
      the neonatal cranial ultrasound scans. Binocular field sizes were assessed using
      kinetic arc perimetry. Binocular grating acuity was tested by means of the
      prototype version of the acuity card procedure. Results were compared with norms
      obtained in control fullterms in earlier studies. Infants were tested at 6 weeks,
      6, 6, 9 and 12 months of age from the expected term date. Twenty-two of these
      infants were retested at 2 1/2 years of corrected age. Visual field size and
      visual acuity estimates of (both AGA and SGA) low-risk, VLBW preterms and control
      fullterms overlapped at all test ages, except for a slight but significantly
      faster development of the upper and the lower visual field at 6 weeks corrected
      age in the preterm group. These results indicate that for clinical purposes
      visual experience before the expected term date has not only no measurable effect
      on the normal development of behavioural acuity, but also no accelerating effect
      on the development of peripheral vision.

PMID- 1388796
TI  - Texture segregation in infants and children.
AB  - Segregation of textures based on differences in line orientation and blob size
      was tested in adults, infants and children, with a forced-choice preferential
      looking technique. Preference for a figure defined by differences in blob size
      already occurs in 2-month-old infants. In contrast, preference for a figure
      differing from the background by the orientation of its elements emerges at the
      end of the first year of life and becomes adult-like by school age.

PMID- 1388797
TI  - The Rotterdam C-chart: norm values for visual acuity and interocular differences
      in 5-year-old children.
AB  - Common C-charts are often not suitable for developmental studies and assessment
      of visual acuity in young and visual impaired children, because of unequal steps
      between lines, uncomparable crowding, inadequate number of large optotypes on the
      first line and ceiling effects. Therefore a new C-chart (the Rotterdam C-chart)
      was developed on which optotypes on successive lines decreased in 1/3-octave
      steps (0.1-log steps) and on which crowding was comparable over the entire chart.
      Norm values for binocular and monocular visual acuity at test distances of 6 m
      and 40 cm and norm values for interocular acuity differences in 5-year-old
      children were determined by testing 201 5-year-olds with this chart. Results were
      compared to those obtained in 24 young adults. Although mean binocular and
      monocular acuity of the 5-year-olds were significantly lower than in adults, the
      distribution of acuity assessments were similar in the children and adults.
      Therefore, the Rotterdam C-chart seems suitable for developmental studies and for
      the assessment of visual acuity in young and visually impaired children.

PMID- 1388798
TI  - The development of parafoveal and mid-peripheral human retina.
AB  - The morphological development of parafoveal retina (1-1.5 mm from the foveal
      center) and the mid-peripheral (4 mm from the foveal center) human retina has
      been studied from fetal (F) 26 weeks to adulthood. At both retinal points, all
      layers and neuronal types are present at F26 weeks. In parafovea at F26 weeks
      photoreceptors have only a rudimentary inner segment and no outer segments. Short
      outer segments are present on both rods and cones at F36 weeks. By postnatal (P)
      5-8 days the inner retina is relatively mature. Photoreceptors have elongated
      basal axons which cause the photoreceptor layer to become much thicker than in
      prenatal retina. At birth cone inner segments are untapered, but rod inner
      segments have already reached their adult width of 2 microns. Both rod and cone
      inner and outer segments are 30-50% of adult length. By 13 months both inner and
      outer retina are mature appearing, with the photoreceptors accounting for half
      the retinal thickness due to the elongation of the fibers of Henle. Cone outer
      segments elongate up to P5 years and rod outer segments to P13 years. At mid
      peripheral or rod-ring retina outer segments are present on rods at F26 weeks and
      on cones at F36 weeks. At birth the inner retina is adultlike. The outer
      plexiform layer becomes thicker up to P45 months due to the elongation of fibers
      of Henle. At birth both rod and cone mid-peripheral inner segments are slightly
      longer and outer segments are 50% longer than in parafoveal retina. By P5 years
      mid-peripheral rod outer segments are slightly longer than in parafoveal retina,
      and this changes little thereafter. This anatomical study has found that the
      photoreceptors in peripheral rod-ring retina develop earlier than those in more
      central retina, and in turn parafoveal photoreceptors develop well in advance of
      foveal cones. This suggests that human neonates may utilize more peripheral
      retinal regions for some aspects of visual function before foveal cone vision
      becomes dominant.

PMID- 1388799
TI  - Development of accommodation and convergence in infancy.
AB  - Paraxial photorefraction was used to assess the development of accommodation and
      convergence in a large sample of infants under 1 year of age. The infants viewed
      small dolls placed at various distances (200-25 cm). The majority of infants at
      all ages demonstrated appropriate convergence for target distance, regardless of
      manifest refractive error. However, accommodation lagged behind convergence in
      development. Infants under 2 months tended to demonstrate either flat
      accommodation responses with a fixed plane of focus at around 30 cm, or
      accommodated appropriately for near targets, but failed to relax their
      accommodation sufficiently for the more distant targets. Thus, the focussing
      error increased with increasing target distance. Since the manifest refractive
      error was estimated by extrapolating the accommodation function to 0 diopters
      demand, these infants demonstrated spuriously myopic behavior. After 2 months,
      the majority of infants showing emmetropic behavior had accommodation responses
      that changed appropriately with target distance. However, infants with myopic or
      hyperopic manifest refractive errors displayed a variety of accommodative styles.

PMID- 1388801
TI  - Detection and maturation of VEP albino asymmetry: an overview and a longitudinal
      study from birth to 54 weeks.
AB  - The genetic anomaly in albinism prevents adequate melanin metabolism within the
      fetal eye cup and stalk. This results in severe disruption of pre- and postnatal
      retinal development and the condition of abnormal temporal retinal projections.
      The obligate misrouting of retinal-geniculate-cortical projections in albinism
      can be detected in the topographical representation across the occiput of the
      visual evoked potential (VEP). Age-dependent misrouting detection methods are
      described which yield 100% detection rates with zero false positives across the
      life span. By combining appropriate state-defined neonatal recording procedures
      with the albino infant VEP test paradigm, the presence of aberrant optic pathway
      projections was observed in a 5-day-old full-term infant. Maximum asymmetry was
      observed within a long-latency window of the response which shifted during the
      postpartum period to shorter latencies. Longitudinal studies show two specific
      latency regions of significant VEP asymmetry. The first occurs within 40-70 ms
      after stimulus onset and remains constant across the age range. The second, more
      robust, cluster of asymmetry occurs within a longer latency window and shows an
      age-related shift towards shorter latencies. The decreasing latency of this
      asymmetry is concomitant with normal maturational changes of the evoked response.
      These results show that VEP misrouting can be extended to reliable albino
      diagnosis within the neonatal period and to the assessment of visual maturation.

PMID- 1388800
TI  - Light and the neonatal eye.
AB  - The lighting environment where the baby born prematurely is placed is different
      from that experienced in utero. As early exposure to light may affect the
      immature visual system we have attempted to quantify the neonatal ocular light
      dose. Lighting surveys performed in 7 neonatal units (NNUs) suggested that mean
      unit illuminance was 470 lux (range 192-890 lux) and intensive care areas within
      the NNU were significantly brighter than their corresponding low dependency
      nurseries. The spectral power distribution of fluorescent lights in NNUs was
      weighted towards the blue end of the spectrum. Datalogging studies demonstrated
      that between about 30% and 98% of environmental light was incident on the eyelid,
      which acts as a predominantly red-pass filter, permitting 21% transmission at 700
      nm with less than or equal to 5% transmission at 580 nm. Eye-lid opening
      frequency was quantified: 45% less than or equal to 26 weeks gestational age and
      decreasing to 7% at 28 weeks gestational age. The onset of the pupillary reflex
      to light was between 30 and 34 weeks postmenstrual age, the mean diameter was
      3.46 mm before this event and 3.02 mm afterwards. Retinal irradiance values
      calculated from these data show that it is a function of postmenstrual age.
      Further studies are required to determine its effect on the immature visual
      system.

PMID- 1388802
TI  - Early development of the subcortical and cortical pathway involved in optokinetic
      nystagmus: the cat as a model for man?
AB  - The optokinetic reflex undergoes qualitative changes during the first postnatal
      weeks in kittens or months in human babies. Under monocular stimulus conditions,
      a clear preference for temporonasal stimulus directions at moderate velocities is
      replaced by a symmetrical, broad velocity range horizontal optokinetic nystagmus
      (OKN) over these periods. Evidence is presented for the cat that development
      changes in OKN can be related to maturation of neuronal response properties in
      the nucleus of the optic tract (NOT) in the pretectum. NOT cells in 3-week-old
      kittens are already direction-selective but all of them are exclusively or
      predominantly driven by the contralateral eye. Only starting with the 4th week of
      life NOT cells become more binocular and respond to a broader spectrum of
      stimulus velocities. This step in maturation coincides with the time when the
      cortical input to the NOT becomes functional.

PMID- 1388803
TI  - Neuroimaging and functional outcome of neonatal leukomalacia.
AB  - Leukomalacia is a major cause of neurological impairment in the high-risk
      newborn. It can be identified during the early postnatal period by means of
      ultrasound (US) imaging of the brain, through the anterior fontanel. Magnetic
      resonance imaging (MRI) permits an optimal differentiation of brain tissue and of
      its abnormalities, without resorting to ionizing radiation or intravenous
      contrast. It is particularly appropriate for following the evolution of
      leukomalacia, after fontanel closure. Ninety-five fullterm and preterm infants
      with cystic and non-cystic leukomalacia, documented by US, were clinically
      followed-up until at least 12 months of corrected age. Thirty-two had a severe
      neurological outcome (mainly cerebral palsy, sometimes associated with mental
      retardation and/or cerebral visual impairment). The prognosis was worse in cystic
      leukomalacia than in prolonged flare. Electroencephalogram (EEG) carried out in
      the first 2 weeks of life provided valuable indexes of further outcome,
      especially for US findings of more uncertain prognosis. MRI was carried out at
      around 12 months of corrected age, by means of an apparatus operating at 0.5
      Tesla. The main categories of abnormalities observed were the following: cystic
      lesions, enlarged ventricles with irregular outlines, delayed myelination, high
      intensity areas in the long TR (repetition time) images within the white matter,
      cortical atrophy. MRI findings correlated well with the results of US imaging and
      often with motor, cognitive and visual impairments. Nevertheless, clinical
      features cannot be predicted by neuroimaging alone and a comprehensive approach,
      including longitudinal functional and electrophysiological testing, is highly
      recommended.

PMID- 1388805
TI  - On the onset of eye-head coordination in infants.
AB  - Head movements have been studied in newborns, during a visual pursuit and in
      relation with ocular movements, in order to know whether head movements help the
      ocular activity or impede it. The infants were tested three times during the
      first month of life. They were placed in a seated position, with the head held
      upright, but free to move. The results provided evidence that eyes and head were
      directionally coupled at as early as 2 weeks and that the interval between eye
      and head rotation decreases from the age of 2-4 weeks. This suggests that the
      beginnings of ocular-motor coordination are present from the first month of life
      in human infants.

PMID- 1388804
TI  - OKN asymmetries in orthoptic patients: contributing factors and effect of
      treatment.
AB  - Monocular optokinetic nystagmus (MOKN) was measured (EOG) in response to
      horizontally moving square wave gratings (0.2 c/deg, 27 and 35 deg/s) in 58
      children with amblyopia and/or strabismus (experimental group); the data were
      compared with that collected from 24 children (aged 3-8 years) with no visual
      problems (control group). We found OKN asymmetries most often associated with
      strabismus of early age of onset (less than 2 years). In these children the MOKN
      asymmetry often occurred in both eyes. In children with later onset strabismus
      the asymmetry was often confined to the amblyopic eyes. We repeated the
      measurements on 18 experimental children after 1-3 years of treatment (patching
      the dominant eye) and compared the results with those recorded in 12 fully
      binocular control children retested after 1-2 years. Large OKN asymmetries before
      treatment were still present after the patching treatment. However there was a
      small, but significant (P = 0.05, t-test), improvement in the nasal-temporal (N
      T) slow-phase velocity in the affected eyes of the experimental group, which was
      not correlated with improvements in visual acuity or linked to the presence of
      strabismus and/or amblyopia. The main contributing factors to asymmetric OKN
      affecting both eyes of early onset strabismus seem to be to poor binocularity
      which would not improve during patching treatment. OKN asymmetries in amblyopic
      eyes may also result from reduced cortical sensitivity from that eye, which may
      be minimally improved by patching treatment. Our results suggest a shorter
      sensitive period of development for OKN pathways than for the development of
      cortical visual pathways.

PMID- 1388806
TI  - Results of photorefractometric screening for amblyogenic defects in children aged
      20 months.
AB  - This report evaluates the validity of a preventive programme in a population
      which underwent refractometric screening at the ages of 20 months and 4 years. In
      1987, 1,046 children born in 1985 in the territory of the Veneto National Health
      Unit No. 19 were invited to undergo screening for amblyogenic factors such as
      meridional hyperopia greater than or equal to +2.50 diopters (D), myopia less
      than or equal to -2.50 D, anisometropia greater than or equal to 2 D, opacity of
      the dioptric media and strabismus. The test method was non-cycloplegic
      photorefractometry (PhR). Seven hundred and ninety-five children were tested
      (76%); positive cases underwent subsequent cycloplegic autorefractometry (AR) and
      corrective lenses were prescribed as necessary. In 1989, an eye test was
      performed on 653 children who had taken part in the previous PhR screening and on
      350 similar children who had not: the test included evaluation of visual acuity,
      stereopsis and AR. An eye with a corrected visual acuity of less than 0.7 was
      considered amblyopic. PhR demonstrated a sensitivity of 80%, a specificity of 96%
      and a positive prediction rating of 46% in the identification of amblyogenic
      factors. The prevalence of amblyopia at 4 years of age in the group which had
      undergone previous screening was 1.07% vs. 2.57% in the group which had not (P:
      not significant). The progress of the myopia was studied in a group with full
      optical correction used continuously (Group A) and in a control group under
      corrected by at least 1.5 D (Group B).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388807
TI  - Acuity card procedures and the linearity of grating resolution development during
      the first year of human infants.
AB  - Since the early times of preferential looking (PL), improvement of procedures to
      test visual resolution in infants has reached the point where the technique is
      spreading to clinical practice as it is applicable to a large range of age with a
      high degree of reliability. Acuity cards allow estimation of bi- and monocular
      acuity in a few minutes. Data from the literature, obtained with various PL
      techniques and procedures are compared to explain some incongruities. Procedures
      for presentation of the cards and criteria for threshold determination can
      greatly bias the data when they do not take into account the infant's behavioral
      requirements. To test the linearity of the development of visual resolution, a
      series of grating acuity measurements was performed on a population of 11 normal
      infants, regularly tested during their first year of life in optimal conditions.
      It was observed that: (1) grating acuity develops very regularly during the first
      year, (2) the two eyes never differ from each other by more than the smallest
      difference measurable with the equipment used (one half-octave), (3) binocular
      acuity appears to slightly exceed monocular acuity. These results stress the need
      for early detection of deviation from the norm and prompt therapeutic action.

PMID- 1388808
TI  - Conditioning, habituation and behavioral reorganization factors in chronic
      cocaine effects.
AB  - Rats were administered cocaine (50.0 mg/kg i.p.) daily for 7 days in a Pavlovian
      paradigm either immediately prior (paired group) or 30 min following (unpaired
      group) a 20-min placement in an open field test environment. After 7 days of drug
      withdrawal, the animals were retested 3 days apart, once with saline and once
      with cocaine (50 mg/kg). Measurement of locomotion as distance traversed (m)
      revealed a higher level of locomotion in the paired group on all test trials.
      Analysis of the paired vs. unpaired differences indicated an antihabituation
      effect of cocaine rather than a hyperlocomotion or a conditioned locomotor
      effect. Rotation pattern analysis for each animal showed a new frequency
      distribution of rotations across four categories of diameter size in the paired
      but not in the unpaired group by Day 5. This new pattern was characterized by a
      shift in skewness toward large greater than or equal to 55 cm diameter rotations.
      These qualitative changes in rotation pattern point to a context specific
      behavioral reorganization process in response to repeated cocaine drug treatment.

PMID- 1388809
TI  - Effects of medial and lateral septal lesions on acquisition of a place and cue
      radial maze task.
AB  - Rats with lesions limited to either the medial septal (MS) or dorsolateral septal
      (LS) nuclei were trained on a place and cue version of the radial maze using a
      procedure that permits determination of both reference memory (RM) and working
      memory (WM). Following training the presence or absence of hippocampal theta for
      MS and LS groups was determined. The results showed that both MS- and LS-lesioned
      rats were impaired in acquisition. Specifically, the pattern of results indicated
      a general impairment in working memory that was found on both the place and cue
      tasks together with impaired acquisition of the place (but not the cue) task.
      While both septal lesion groups evidenced a similar impairment, rats in the MS
      group made more errors than LS rats on several components of the tasks.
      Electroencephalographic recordings revealed that hippocampal theta was not
      affected in the LS group but was abolished in rats with MS lesions. Thus, it
      appears that the functional role of the septo-hippocampal system cannot be fully
      described by a single mechanism or process but rather several processes seem to
      be affected when the septal area is damaged.

PMID- 1388810
TI  - Unilateral lesion in the tuberomammillary nucleus region: behavioral asymmetries
      and effects of histamine precursor.
AB  - The subnuclei of tuberomammillary nucleus are located in the posterior part of
      the hypothalamus adjacent to the basolateral surface of the mammillary bodies.
      The neurons of this nucleus innervate extensive parts of the brain with several
      transmitters, particularly with histamine. In fact, they represent the only
      source of histaminergic projections in the brain. The present study deals with
      the effects of a lesion in this region on behavior. Unilateral electrolytic
      direct current (DC) lesions in the tuberomammillary nucleus led to an asymmetry
      in thigmotactic scanning; i.e., at 11 days, but not 1 day postlesion, the rats
      scanned the walls of an open field more with the vibrissae contralateral to the
      lesion than with those of the ipsilateral side. Furthermore, they emitted more
      ipsiversive than contraversive wide angle turns. The behavioral asymmetries are,
      in general, opposite in direction to those induced by lesion of the neighboring
      lateral hypothalamus and substantia nigra, indicating that they are specific to
      the tuberomammillary region destroyed. Application of the histamine precursor
      histidine led to a compensation of these asymmetries, suggesting that the
      tuberomammillary's histaminergic efferents are functionally related to the lesion
      induced behavioral effects.

PMID- 1388811
TI  - Duration of retrograde amnesia induced by tetrodotoxin inactivation of the
      parabrachial nuclei is inversely related to the intensity of footshock in rat's
      passive avoidance response.
AB  - Previous work has demonstrated that in rats post-trial bilateral functional
      blockade of the parabrachial nuclei by local injection of tetrodotoxin (10 ng in
      1 microliter) partially disrupts retention of an overtrained passive avoidance
      response. The time-course of functional blockade disrupting effects on passive
      avoidance response has been studied by altering both the acquisition-tetrodotoxin
      injection interval and footshock intensity as independent variables. When week
      footshocks (0.8 mA) were delivered, functional ablation of the parabrachial
      nuclei was still effective when induced up to 8 days after acquisition training.
      On the other hand, when rats were shocked with the stronger stimuli (1.2 mA), 2
      days after acquisition functional ablation was no longer effective. The results
      are discussed in terms of unconditioned stimulus (US) intensity and engram
      consolidation.

PMID- 1388812
TI  - Raised glucose levels enhance scopolamine-induced acetylcholine overflow from the
      hippocampus: an in vivo microdialysis study in the rat.
AB  - Behavioural studies in both humans and animals have shown that an acute rise in
      circulating glucose levels at or around the time of training enhances subsequent
      retention performance and can also afford protection from the amnesia produced by
      posttraining injections of scopolamine. In an attempt to directly investigate the
      neurochemical basis for these effects of glucose we have tested the hypothesis
      that raised glucose levels may enhance acetylcholine (ACh) synthesis and release
      in the brain during conditions of increased neuronal activity, induced either by
      training or pharmacological challenge, via a microdialysis study using rats.
      Microdialysate concentrations of ACh overflow from the hippocampus of fasted rats
      induced by i.p. injections of scopolamine (1 mg/kg) combined with concurrent s.c.
      injections of either glucose (2 g/kg) or saline were compared in successive 15
      min samples using an on-line HPLC system. Scopolamine injections resulted in an
      immediate 10-20-fold increase in hippocampal ACh overflow which subsequently
      progressively declined over a 4-h period to pretreatment baseline levels. The
      combined injection of glucose with scopolamine resulted in a highly significant
      enhancement (19.4%; P less than 0.01) in ACh content of the first two samples as
      compared to saline-injected controls. These results provide the first direct
      experimental evidence that raised glucose levels, via increased availability of
      acetyl-coenzyme A (acetyl-coA), transiently facilitates ACh synthesis and release
      during conditions of increased neuronal activity. This enhancement of ACh
      availability during states of cholinergic neuronal activation may underlie the
      previously observed facilitatory effects of glucose on memory performance and its
      protection from scopolamine-induced amnesia.

PMID- 1388813
TI  - The spatial distribution of attention in S-R compatibility.
AB  - In certain choice reaction time experiments the subjects, although not
      specifically instructed to do so, perform a parcellation of space into right and
      left components. Previous research has shown that when the stimulus locations are
      marked on the screen, the subdivision of space into right and left halves is
      bound to the point where the subject has been instructed to focus selective
      attention. It is not known whether, in the absence of specific instructions,
      subjects are able to focus selective attention between stimulus locations when no
      marker is present. We tried to clarify this problem by introducing a 'probe'
      stimulus that could map the spatial distribution of attention in subjects engaged
      in a compatibility task. The results suggest that, in the absence of visual cues
      marking the stimulus positions, attention is kept in the disengaged modality
      before the presentation of the stimuli. In this state of disengagement a powerful
      tendency to orient to the rightmost side of the display, within each visual
      field, is apparent. Various interpretations of this finding are discussed.

PMID- 1388814
TI  - Effect of lesions in the ectostriatum and Wulst on species and individual
      discrimination in pigeons.
AB  - Pigeons were trained on species (pigeon vs. quail) or individual (pigeon vs.
      pigeon) discrimination in an operant chamber with a video screen. Still video
      images were used as discriminative stimuli. After the pigeons had accomplished
      the discrimination tasks, they received lesions of the Wulst or the ectostriatum.
      While damage to the Wulst did not disrupt either task, the ectostriatal damage
      caused deficits selectively in individual discrimination. These dissociations
      between the tasks and between the lesion sites are comparable to the previous
      experiments on natural and pseudoconcept. Species discrimination seems to share
      common brain mechanisms with other natural concept discrimination.

PMID- 1388815
TI  - Copulatory stimuli in rats induce heat abbreviation through effects on genitalia
      but not through effects on central nervous mechanisms supporting the steroid
      hormone-induced sexual responsiveness.
AB  - Male copulatory stimuli in various animal species abbreviate the length of the
      period of their female conspecifics' heat. Such effect can be explained in some
      species as the result of copulation-induced alterations in ovarian hormone
      secretion (e.g. reflex ovulators). Other species require a different explanation:
      specifically, interactions in the hypothalamus between effects of steroid
      hormones and inhibitory neural afferents from the genital area have been
      hypothesized to play a role in some laboratory animals such as guinea pigs,
      hamsters and rats. However, the evidence in support of heat abbreviation through
      copulatory stimuli in rats is at best equivocal. There is obvious need for its
      unequivocal demonstration prior to any further analysis of the potential
      mechanism of action. The present study intended to find a model in support of the
      concept of 'centrally induced' heat abbreviation in rats. Virgin rats during
      'natural heat' were examined with or without allowing them the opportunity to
      pace male copulatory activities. Ovariectomized, steroid hormone-treated rats
      were studied with minor or ample experience with sexual activities in prior tests
      and, also, with or without the opportunity to 'pace' male sexual acts. None of
      the experimental models revealed unequivocal support for detrimental effect of
      large numbers of intromittive copulations on 'central mechanisms' regulating heat
      duration. It rather seemed that frequent intromittive copulations and ejaculates
      affected the 'peripheral' genital tract (vulva, vagina, cervix) making further
      copulation of a highly aversive quality so that sexual encounters were avoided or
      prevented. This effect was noticed with great inter-individual variability. The
      conclusion is drawn that rats do not show the counterpart of heat abbreviation
      reportedly occurring rapidly and reliably in guinea pigs after a limited amount
      of vaginal/cervical stimulation through copulation or insertions of a glass-rod.

PMID- 1388817
TI  - Photothrombotic lesions of the frontal cortex impair the performance of the
      delayed non-matching to position task by rats.
AB  - The effects of photochemically induced lesions of the frontal cortex on the short
      term memory capacity of the rat have been investigated using the delayed non
      matching to position task. Pretrained animals received lesions and were tested 4
      days after surgery and twice per week for 3 weeks. The lesions produced a
      profound impairment of performance of this task which was still evident 3 weeks
      after surgery. Spontaneous locomotor activity was recorded 7 days after surgery
      and no difference was found between the control and lesion group. These effects
      indicated a generalized disruption of performance of this task in the absence of
      motor dysfunction. These results suggest that photothrombotic lesions of the
      frontal cortex can produce reliable, long-term behavioural deficits.

PMID- 1388816
TI  - 6-Hydroxydopamine lesions of the medial prefrontal cortex fail to influence
      cocaine-induced place conditioning.
AB  - This study investigated the involvement of medial prefrontal cortex (mPFC)
      dopamine in cocaine place conditioning using a totally balanced place
      conditioning design. Presynaptic dopamine terminals of the mPFC were lesioned by
      bilaterally infusing the selective neurotoxin 6-hydroxydopamine (6-OHDA). These
      lesions significantly depleted dopamine (-83%) and norepinephrine (-70%) in the
      mPFC but there were no significant reductions in either the nucleus accumbens or
      in the caudate-putamen compared with sham-operated controls. Furthermore,
      serotonin levels were not affected in any of the brain regions investigated.
      These lesions failed to attenuate place conditioning induced by the
      intraperitoneal (i.p. 10 mg/kg) administration of cocaine when compared to sham
      lesioned controls. In addition, there were no significant differences in
      spontaneous locomotor activity between the two groups during the preconditioning
      phase or the test phase. These results suggest that 6-OHDA lesions which produced
      profound depletions of dopamine and norepinephrine in the mPFC did not alter the
      rewarding efficacy of cocaine as measured by the place conditioning paradigm.

PMID- 1388818
TI  - Properties of trypsin and of acid phosphatase immobilized in sol-gel glass
      matrices.
AB  - Trypsin and acid phosphatase-containing silica sol-gel glasses were obtained by
      mixing a solution of an enzyme with polyethylene glycol (PEG) 6000 and
      tetramethoxy orthosilicate at room temperature, followed by gelation and drying.
      Activity of the immobilized trypsin toward small substrates, such as N-benzoyl-L
      arginine-4-nitroanilide at its Km, for the best preparations equaled that of the
      soluble enzyme. Polylysine (M(r) less than or equal to 13,000) and aprotinin
      (M(r) = 6,500) inhibited this activity. Larger polylysines as well as soybean
      trypsin inhibitor (M(r) = 20,100) were ineffective. The sol-gel-entrapped trypsin
      activity was stable when sol-gel glasses were incubated at ambient temperature
      (pH 7.5) for several months. In comparison, trypsin, immobilized in sol-gel glass
      by surface adsorption and incubated under the same conditions overnight, was
      completely autodigested. The firm interaction between the protein molecules and
      the silica matrix stabilized the enzymes. Thus, the half-life of sol-gel
      entrapped acid phosphatase at 70 degrees C (pH 8.0) was two orders of magnitude
      larger than that of the enzyme in solution. Transparent, mechanically and
      chemically stable bioactive sol-gel glasses may be used for the development of
      robust on-line biochemical photodetection sensors and for the purposes of
      chemical catalysis.

PMID- 1388819
TI  - Interaction of carboplatin with carrier human erythrocytes.
AB  - The antineoplastic drug Carboplatin (CBDCA) was encapsulated in human
      erythrocytes by means of transient hypotonic hemolysis, followed by isotonic
      resealing. Up to 5 mg/ml of packed cells could be entrapped, with about 70% cell
      recovery. In vitro incubation of the CBDCA-loaded erythrocytes in autologous
      plasma caused a very slow release of the drug from the cells (12% approximately
      in 3 h). The encapsulation conditions, performed at a low hematocrit, in order to
      obtain high amounts of the drug inside the carriers, impaired the metabolic
      properties of the loaded erythrocytes significantly. In particular, an almost
      complete disappearance of GSH was observed. Analysis of the intraerythrocytic
      metabolism of CBDCA showed that, in spite of its relatively high stability in
      aqueous solutions, in hemolysates and in the loaded erythrocytes a significant
      percentage of CBDCA is rapidly converted to other species that still retain an
      antiproliferative activity in vitro. This fast conversion could be extensively
      inhibited by previous conversion of oxyhemoglobin to methemoglobin or
      carbomonoxyhemoglobin, suggesting an important role of heme iron in this process.
      Encapsulation of CBDCA in selectively targeted human erythrocytes may represent a
      therapeutic strategy for increasing the drug concentration in specific organs,
      notably liver.

PMID- 1388820
TI  - Biosynthesis of cholesterol linoleate by polyethylene glycol-modified cholesterol
      esterase in organic solvents.
AB  - Cholesterol esterase modified with polyethylene glycol was able to dissolve in
      some highly hydrophobic solvents such as benzene and toluene, and catalyze the
      synthesis of cholesterol linoleate with time dependency in the reverse of the
      usual reaction in aqueous solvents. Enzymatic cholesterol linoleate synthesis
      followed Michaelis-Menten kinetics which depended on the concentration of
      cholesterol and linoleic acid. When more than 20 mM of both substrates was used,
      the specific activity in this esterification was 200-250 nmol/min/mg protein. The
      apparent Km value for cholesterol and linoleic acid was 3.7 and 7.6 mM,
      respectively. The possibility of using such a modified enzyme for the synthesis
      of less stable cholesterol esters is discussed.

PMID- 1388821
TI  - Mechanistic and structural studies on Rhodococcus ATCC 39484 nitrilase.
AB  - Rhodococcus ATCC 39484 produced a nitrilase when induced with isovaleronitrile.
      The enzyme was obtainable pure in milligram amounts, had a subunit Mr of 40 kDa,
      and demonstrated a substrate-induced activation related to aggregation of
      subunits to form a 560-kDa complex. The enzyme had a broad substrate specificity,
      had a pH optimum of 7.5, was stable up to 40 degrees C, and had one disulfide
      bridge and two free cysteine residues, one of which appeared to be catalytically
      essential. The N-terminal sequence was determined and found to have 78.3%
      homology, in a 23-residue overlap, with Klebsiella ozaenae nitrilase. The enzyme
      was inhibited competitively by benzylamine and benzaldehyde and irreversibly by
      benzyl bromide. However, benzyl bromide was shown to be nonspecific, causing
      multiple alkylation. Acid quenching of enzyme-substrate mixtures allowed for the
      detection of covalent enzyme-substrate complexes using mass spectrometry. The
      covalent intermediate is suggested to be either a thioimidate or an acylenzyme
      and a reaction mechanism consistent with this observation and also the inhibitor
      results is proposed. The rate of breakdown of the covalent intermediates was
      found to be rate limiting even for substrates with undetectable rates of
      hydrolysis or those with very slow rates of intermediate formation. For
      phenylacetonitrile, a poor substrate, in addition to acid, approximately 2% of
      the product was the corresponding amide. This result suggests that a tetrahedral
      intermediate is formed which, for selected substrates, can break down anomalously
      to produce amide in place of the normal acid product. Under the conditions used
      in this study all other substrates tested were converted to acid.

PMID- 1388822
TI  - Effect of 5,7-unsaturated sterols on ethanol tolerance in Saccharomyces
      cerevisiae.
AB  - Structural membrane lipids are known to contribute to the high ethanol resistance
      of Saccharomyces cerevisiae (2, 4, 17). By manipulating the yeast cellular sterol
      level by changing the carbon-to-nitrogen source ratio in the chemostat growth
      medium, high delta 5,7-sterol levels were found to increase the resistance of
      yeast populations to ethanol-induced death. The resistance of the erg2 (delta 8--
      -delta 7-sterol isomerase) mutant to ethanol-induced death was generally
      comparable with that of the delta 5,7-sterol-synthesizing strain. In contrast,
      the sensitivity of anaerobic growth to inhibition by ethanol was higher in the
      erg2 mutant in comparison with the delta 5,7-sterol-synthesizing strains but a
      high level of those sterols increased the vulnerability of anaerobic growth to
      ethanol inhibition.

PMID- 1388823
TI  - The zygomatico-temporal approach to the skull base: a critical review of 11
      patients.
AB  - The zygomatico-temporal approach to the base of the skull is a relatively new but
      established surgical technique. The approach involves the removal of the
      zygomatic bone to provide access to the skull base, middle cranial fossa,
      parasellar region and interpeduncular cistern with minimal brain retraction. An
      excellent view of the bifurcation of the basilar artery and suprasellar region is
      provided. The outcome of 11 patients undergoing this procedure is reported with
      particular reference to the post-operative morbidity and the cosmetic result.

PMID- 1388824
TI  - Does thrombin prevent cerebral vasospasm following aneurysmal subarachnoid
      haemorrhage?
AB  - Fibrinopeptide A (FPA) levels which have been shown to be a quantitative index of
      thrombin generation, were measured in blood and cerebrospinal fluid (CSF) samples
      from patients following subarachnoid haemorrhage (SAH) and from a control
      population. The levels found in samples obtained in patients following SAH are
      compared with those found in controls and also correlated with clinical grade on
      admission as assessed by the Glasgow Coma Score and the World Federation of
      Neurological Surgeons' grading system, and with the amount of subarachnoid blood
      seen on CT, the occurrence of ischaemic deterioration, the occurrence of low
      density change on CT, the presence of vasospasm on angiography, clinical outcome
      as assessed by the Glasgow Outcome Score 3 months following the ictus, and the
      incidence of ischaemia as a cause of death or disability as assessed 3 months
      following the ictus. The levels of FPA found in blood and CSF from patients
      following SAH were significantly raised when compared with those found in
      controls. There was significant correlation between blood FPA levels and the
      amount of subarachnoid blood seen on initial CT. CSF FPA levels had a
      statistically significant correlation with outcome as assessed at 3 months post
      ictus. No statistically significant correlation was found between blood or CSF
      FPA levels and any of the other variables studied.

PMID- 1388825
TI  - Mechanical complications of the reservoirs and flushing devices in ventricular
      shunt systems.
AB  - Complications of valve reservoirs or flushing devices are seldom reported as a
      cause of shunt malfunction. The authors document their experience in six cases of
      mechanical complications of shunting devices. Two cases presented with collapse
      and intracranial migration of the valve reservoir, a complication that has not
      been reported previously. In two cases, the plastic dome became disconnected from
      the metallic base of the reservoir. A fifth patient, with an integral shunt
      system, showed a fracture in the soldered join of the distal tube to the
      reservoir dome. The last patient had the valve reservoir partially collapsed by
      bone growth at the time of shunt revision.

PMID- 1388826
TI  - An in vitro study of the effect of photodynamic therapy on human meningiomas.
AB  - Despite being benign CNS tumours, meningiomas are not always curable and the
      likelihood of recurrence depends upon the completeness of initial removal.
      Adjuvant therapy for incompletely resected meningiomas is generally
      unsatisfactory and such lesions continue to pose difficult management problems.
      Photodynamic therapy (PDT) has been employed in the management of recurrent
      cerebral gliomas but its activity against meningiomas has not been specifically
      studied. An in vitro study of the effects of PDT against a variety of meningiomas
      was therefore conducted. It was found that PDT using haematoporphyrin derivative
      as a photosensitizing drug showed dose-dependent activity against a variety of
      histological subtypes of meningioma. The activity of PDT against meningiomas
      should be investigated further and may eventually provide a useful form of
      adjuvant therapy for incompletely resected lesions.

PMID- 1388828
TI  - Computer-generated titanium cranioplasty: report of a new technique for repairing
      skull defects.
AB  - A review of 40 cases of titanium cranioplasty fabricated from impressions taken
      of the defect through the patient's scalp in the conventional way showed that 23%
      were ill-fitting and 41% of frontal plates had a poor aesthetic result.
      Attributable factors were difficulty in defining the defect border accurately and
      limited information of the surrounding tissue architecture which led to strains
      produced during insertion. Inadequate communication between surgeon and
      prosthetist compounded these difficulties. A prospective study of six cases
      fabricated from CT computer-generated models of challenging cranial defects
      appears to show significant improvements in plate design, resulting in better
      plate adaptation, stability and aesthetic contour. Plate insertion was rapid
      (mean time 27 min) thereby minimizing operating time. This paper also discusses
      the advantages of the enhanced information derived from CT and describes the
      potential for pre-craniotomy template and matching cranioplasty, thereby
      permitting a one-stage procedure.

PMID- 1388827
TI  - Pressure and blood flow in pituitary adenomas measured during transsphenoidal
      surgery.
AB  - In 48 patients undergoing transsphenoidal surgery for pituitary adenoma, the
      intrasellar pressure was recorded during surgery. In 14 patients, adenoma blood
      flow was measured with the technique of local injection of 133xenon. Median
      intrasellar pressure was 30 mmHg (range 8-62), n = 48, and median adenoma blood
      flow was 8 ml/100 g/min (range 0-37), n = 14. In two patients, blood flow in the
      anterior pituitary gland was measured, and values of 26 and 22 ml/100 g/min were
      obtained. The finding that intrasellar pressure is above central venous and
      intracranial pressure suggests the possibility that the adenoma and the anterior
      pituitary gland are supplied not only with venous blood, but receive an
      additional arterial supply at a less  than normal arterial pressure. In three
      cases perfusion pressures that caused arrest of adenoma blood flow were found,
      and these observations are discussed with reference to pituitary apoplexy.

PMID- 1388830
TI  - 'Tenting' stitches for the scalp.
AB  - A subgaleal collection of blood or cerebrospinal fluid (CSF) is commonly
      encountered after craniotomy. In spite of the placement of subgaleal drains by
      many neurosurgeons, a collection at this site is frequent and occasionally can
      result in complications. 'Tenting' scalp stitches are described. Three to four
      (or more) stitches are inserted between the galea and the pericranium or between
      the pericranium and the craniotomy flap at the end of the surgical procedure.
      This simple manoeuvre was seen significantly to reduce collections in these
      spaces. To our knowledge, this technique has not been reported in the
      neurosurgical literature, and we strongly advocate its use.

PMID- 1388829
TI  - Intradural spinal cavernomas.
AB  - Intradural cavernomas are rare vascular lesions of the spinal cord. Four cases of
      histologically verified cavernomas of the cord are reported, of which two were
      extramedullary and two were intramedullary in location. Progressive neurological
      deficit was the presenting feature in three cases while one patient had a rapid
      evolution of neurological deficits and was found at surgery to have had bled from
      the extramedullary lesion. All the patients were subjected to surgery and total
      excision of the cavernomas was carried out in each case. While two patients
      improved after surgery the other two remained static. The available literature on
      spinal cord cavernomas is reviewed.

PMID- 1388831
TI  - Chronic extradural haematomas: indications for surgery.
AB  - Non-invasive neuro-imaging has led to the detection of minimally symptomatic or
      asymptomatic chronic extradural haematomas. Our experience and review of the
      literature suggests that, as in the case of chronic subdural haematomas, there is
      development of membranes and liquifaction of the clot which may permit drainage
      of such collections through twist drill or burrholes. The time from development
      and the neuro-imaging chanes on CT and MRI can suggest the age and nature of the
      clot and thus permit timing of surgery so that drainage may be accomplished with
      a minor procedure.

PMID- 1388832
TI  - Cysticercosis producing various neurological presentations in a patient: case
      report.
AB  - We present an unusual case of neurocysticercosis supported by characteristic
      lesions on computed tomography and positive serum and CSF titres. The patient
      came to medical attention on various occasions over a decade with three clearly
      separate neurological presentations (acute psychosis, cerebral infarction, and
      hydrocephalus) before diagnosis was made.

PMID- 1388833
TI  - Oligodendroglioma of the fourth ventricle with intracranial and spinal
      oligodendrogliomatosis: a case report.
AB  - We report a case of oligodendroglioma of the fourth ventricle complicated by
      disseminated intracranial and spinal oligodendrogliomatosis. This is further
      evidence that primary oligodendrogliomas arising in close proximity to the
      cerebrospinal pathway have a predilection for spontaneous dissemination. This
      condition should be considered in the differential diagnosis of hydrocephalus and
      myelopathy.

PMID- 1388834
TI  - Functional recovery after near complete traumatic deficit of the cervical cord
      lasting more than 24 h.
AB  - Two young men presented with a complete cervical cord deficit associated with
      bilateral C4-C5 dislocation and 11 mm encroachment (sagittal narrowing) of the
      spinal canal in one case and near complete cervical cord deficit due to a crush
      fracture of the C7 vertebral body with 9 mm axial compression and 50% antero
      posterior encroachment of the canal in the other case. There was no improvement
      within the first 24 h. Both patients left the hospital walking after open
      surgical realignment and complete cord decompression.

PMID- 1388835
TI  - An 'empty' sphenoid mucocele.
AB  - Sphenoid sinus mucoceles behave as mass lesions producing erosion of adjacent
      bone and cranial nerve palsies. The probable cause is obstruction of the ostia of
      the sinus. We describe a case which was 'cured' inadvertently by a nasal
      polypectomy.

PMID- 1388836
TI  - Hypothermia due to transient hypothalamic dysfunction in tuberculous meningitis
      with hydrocephalus.
AB  - We report two patients with tuberculous meningitis and hydrocephalus who
      developed hypothermia that reversed after inserting a ventricular shunt for the
      hydrocephalus. Pressure on the thermoregulatory centre in the posterior
      hypothalamus near the dilated third ventricle might have been responsible. One
      patient developed hypotension during the transient hypothermia, which persisted
      and proved fatal.

PMID- 1388837
TI  - Resolution of fluent dysphasia following excision of metastatic carcinoma from
      the arcuate fasciculus.

PMID- 1388838
TI  - Cholera as a model for research on mucosal immunity and development of oral
      vaccines.
AB  - During the past year, the extensive investigational use of a recently developed
      oral vaccine against cholera has led to significant advances in our understanding
      of both immunity to cholera and related diarrhoeal diseases, and the mucosal
      immune response in general after oral immunization. The oral cholera vaccine has
      been shown to protect, through its cholera toxin B subunit component, against
      travellers' diarrhoea caused by enterotoxigenic Escherichia coli. The elaboration
      of sensitive new techniques has allowed detailed clonal analyses of the
      activation of specific B and T cells and immunologic memory in intestinal mucosa
      in humans after oral cholera vaccination. These techniques have also been used to
      demonstrate a transient appearance after immunization of specific gut-derived IgA
      antibody-producing cells in the circulation and also, a few days later, in a
      distant mucosal tissue such as the salivary glands.

PMID- 1388839
TI  - Superantigens.
AB  - The endogenous superantigens (the enigmatic minor lymphocyte-stimulating
      antigens) have been identified; they are encoded by integrated mouse mammary
      tumor viruses. The retroviral superantigens appear to be transmembrane
      glycoproteins, and their highly variable extracellular carboxyl terminus is
      responsible for V beta interaction. In spite of intensive efforts the precise
      structure-function relationship for the superantigens is not yet clear. The most
      important consequences of the introduction of the superantigens in vivo are shock
      and T-cell depletion and anergy. The search for novel superantigens related to
      human diseases has started.

PMID- 1388840
TI  - Heat-shock proteins: immunity and autoimmunity.
AB  - Antigens from a wide variety of pathogens have been identified as members of
      conserved heat-shock protein families, sharing upwards of 50% amino acid identity
      with corresponding host-cell proteins. Analysis of the responses to these
      conserved antigens may provide insights into regulation of the immune system
      during infection and autoimmunity.

PMID- 1388841
TI  - Antigen presentation in virus infection.
AB  - Important recent advances have been made in our understanding of antigen
      processing of cytoplasmic antigens and presentation by class I molecules of the
      MHC. Peptide transporter-like molecules encoded within the MHC have been
      characterized and have, by transfection, corrected some of the presentation
      mutant cell lines. The nature of peptide-MHC class I interactions has been
      clarified by further resolution of the HLA A2 and B27 crystals and elution of
      peptides. The differences between antigenicity and immunogenicity for viral
      antigens have been highlighted by studies in transgenic animals.

PMID- 1388842
TI  - Virally induced immunosuppression.
AB  - A mouse model of virus-triggered, T-cell mediated acquired immunosuppression is
      analyzed. Lymphocytic choriomeningitis virus initially infects mostly macrophages
      and antigen-presenting cells; these are destroyed by lymphocytic choriomeningitis
      virus specific cytotoxic T cells resulting in immunosuppression. Similar
      immunopathological mechanisms may play a role in acquired immune deficiency
      syndrome.

PMID- 1388843
TI  - Immunity to schistosomes.
AB  - Significant advances have been made during the past years in our knowledge of
      schistosomiasis, the second major parasitic disease in the world. The highlights
      provide a good illustration of the recent progress made in our understanding of
      immunity in human populations and the regulation of the immune response, and in
      the approach toward a vaccine.

PMID- 1388844
TI  - Malaria: becoming more specific about non-specific immunity.
AB  - For the hundreds of millions of people presently infected with malaria, survival
      may depend on relatively non-specific immune effector mechanisms. Progress has
      been made in understanding the anti-parasitic properties of tumor necrosis factor
      alpha, interferon-gamma and nitric oxide, in defining the parasite toxins that
      induce tumor necrosis factor-alpha production, and in exploring the role of
      cytokines and adhesion molecules in the pathogenesis of cerebral malaria.

PMID- 1388845
TI  - Malaria vaccines.
AB  - The development of an effective malaria vaccine is a feasible goal. Most of the
      vaccines being developed today are subunit vaccines derived from selected
      parasite antigens or their immunologically active fragments. The precise
      characterization of protective immune responses against Plasmodium parasites
      remains a fundamental part of present research aimed at obtaining a malaria
      vaccine(s).

PMID- 1388846
TI  - Old microbes with new faces: molecular biology and the design of new vaccines.
AB  - Rational approaches to the design of live attenuated bacterial and viral
      recombinant vaccine strains are leading to the manipulation of old vaccines and
      the generation of new ones. The two basic problems to be solved are attenuation
      of pathogenic strains, and the stable expression of foreign antigens.

PMID- 1388847
TI  - New carriers and adjuvants in the development of vaccines.
AB  - Different approaches are being followed to enhance the immunogenicity of
      established and newly developed vaccines. Some of them foresee the utilization of
      carrier molecules recognized by the immune systems of a large proportion of the
      human population. Others are directed mainly towards the development of improved
      adjuvants and delivery systems.

PMID- 1388848
TI  - Cellular latency of human immunodeficiency virus type 1.
AB  - The infection of humans by human immunodeficiency virus type 1 is characterized
      by a prolonged stage of clinical quiescence. This clinically asymptomatic period
      may be based, in part, on the development of cell populations within the body
      that maintain human immunodeficiency virus type 1 in a state of latency. Recent
      advances in the understanding of the molecular mechanisms involved in various
      forms of cellular latency of human immunodeficiency virus type 1 have begun to
      shed light on the variable period of asymptomatic infection. The elucidation of
      cellular retroviral latency, in vivo, will also be critical to the design of
      novel therapeutic approaches with which to combat human immunodeficiency virus
      type 1 infections.

PMID- 1388849
TI  - Genetic immunodeficiencies: both the lumpers and the splitters can claim victory.
AB  - Over the last few years, molecular approaches to analysis of genetic
      immunodeficiencies have made it clear that different mutations of the same gene
      may result in very different clinical presentations. On the other hand, a single
      clinical syndrome is sometimes due to mutations in a variety of independent
      genes. In the future, appropriate treatment, particularly gene therapy, will
      depend on a precise genetic diagnosis.

PMID- 1388850
TI  - Immunity to infection.

PMID- 1388851
TI  - Immunodeficiency.

PMID- 1388852
TI  - Social and emotional patterns in adulthood: support for socioemotional
      selectivity theory.
AB  - This investigation explored 2 hypotheses derived from socioemotional selectivity
      theory: (a) Selective reductions in social interaction begin in early adulthood
      and (b) emotional closeness to significant others increases rather than decreases
      in adulthood even when rate reductions occur. Transcribed interviews with 28
      women and 22 men from the Child Guidance Study, conducted over 34 years, were
      reviewed and rated for frequency of interaction, satisfaction with the
      relationship, and degree of emotional closeness in 6 types of relationships.
      Interaction frequency with acquaintances and close friends declined from early
      adulthood on. Interaction frequency with spouses and siblings increased across
      the same time period and emotional closeness increased throughout adulthood in
      relationships with relatives and close friends. Findings suggest that individuals
      begin narrowing their range of social partners long before old age.

PMID- 1388853
TI  - Age and visual field differences in computing visual-spatial relations.
AB  - Age and brain hemispheric differences in visual-spatial performance were
      investigated using 2 versions of categorical and coordinate (metric) spatial
      relations tasks. Thirty-two young adults (M = 19.2 years) and 32 older adults (M
      = 68.8 years) participated. An overall age-related decrement in computing visual
      spatial relations was obtained for lateralized presentations and when items were
      presented centrally. In contrast to some previous findings, there was no evidence
      to suggest differential aging of the right hemisphere in computing visual-spatial
      relations.

PMID- 1388854
TI  - Physical illness and symptoms of depression among elderly outpatients.
AB  - Elderly outpatients were assessed to clarify relations between symptoms of
      depression and physical illness, disability, pain, and selected psychosocial
      variables. Three types of assessments were made: (a) medical evaluations by
      physicians, (b) self-reported symptoms of depression and physical health, and (c)
      demographic and psychosocial data relating to participants' life circumstances.
      Both objective (physician-rated illness symptoms) and subjective (self-reported
      health, activity restriction, and use of pain medications) indicators of health
      accounted for independent variance in symptoms of depression. After controlling
      for these factors, additional variance was explained by health-related concerns
      (e.g., health care expenses, service needs), social support, and "other worries"
      (e.g., feeling useless, becoming a burden to others).

PMID- 1388855
TI  - Age-related differences in memory as a function of imagery processing.
AB  - The effects of aging on imagery production and use--following the learning of
      concrete and abstract words--and their relations to subsequent memory performance
      were explored in 2 experiments. Both experiments demonstrated better free recall
      of concrete than of abstract words (the concreteness effect). Experiment 1 showed
      this superiority to be greater for young subjects only under explicit imagery
      instructions. Experiment 2 revealed that the advantage of concrete over abstract
      words reflects the use of differential imagery production. The results are
      discussed in terms of age differences in imagery utilization and the effects of
      visual processing on recall.

PMID- 1388856
TI  - Category knowledge in Alzheimer's disease: normal organization and a general
      retrieval deficit.
AB  - Three hypotheses that could account for deficits in the retrieval of category
      information in Alzheimer's disease (AD) were evaluated: abnormal organization,
      class- or category-specific vulnerability, and limitation by general factors,
      such as decreased processing speed. Relative to 18 elderly control subjects, 18
      patients with AD produced fewer items in a category fluency task and had longer
      reaction times in a category decision task. The pattern of performance across
      categories on both tasks was normal in the AD group: The same categories elicited
      the most (or fastest) responses in both the control group and the AD group. AD
      patients showed normal performance in ranking of category exemplars by
      typicality. There was no evidence for differential accessibility by category or
      by class of information (animate vs. inanimate). The authors conclude that a
      general factor or factors limit(s) retrievability equally across all categories.

PMID- 1388857
TI  - Mental and physical health of spouse caregivers: the role of personality.
AB  - Although personal resources of caregivers, such as coping skills and social
      support, have been shown to be important in understanding caregiver stress and
      health outcomes, personality traits have not previously been considered. The
      purpose of this study was to examine the association between the personality
      traits of neuroticism and dispositional optimism and mental and physical health
      outcomes. It was predicted that personality would have direct effects, and
      indirect effects through perceived stress, on health outcomes. Participants were
      spouse caregivers of patients diagnosed with Alzheimer's disease. Results showed
      that neuroticism and optimism were significantly related to mental and physical
      health. Furthermore, neuroticism had significant direct effects on all of the
      health outcomes, and substantial indirect effects, through perceived stress, on
      mental health outcomes. Optimism showed stronger indirect than direct effects on
      all health outcomes. These findings demonstrate the importance of including
      personality of the caregiver in theoretical and empirical models of the
      caregiving process.

PMID- 1388858
TI  - Aging, expertise, and narrative processing.
AB  - In a study of how aviation expertise influences age differences in narrative
      processing, young and older pilots and nonpilots read and recalled aviation and
      general narratives. They chose referents for sentences referring to a protagonist
      or minor character mentioned 1 sentence (recent character) or 3 sentences
      (distant character) before this target sentence. All groups chose referents less
      accurately for sentences about distant and minor characters than about recent and
      protagonist characters, perhaps because these referents were less likely to be in
      working memory. Young readers and pilots were more accurate for distant and minor
      character target sentences in aviation narratives, and recalled aviation
      narratives more accurately. Expertise did not reduce age differences. Expertise
      differences may reflect decreased demands on working memory capacity, and age
      declines may reflect reduced capacity.

PMID- 1388859
TI  - Spatial cognition and neighborhood use: the relationship in older adults.
AB  - Measures of spatial cognition, neighborhood knowledge, and neighborhood use from
      the research described by Walsh, Krauss, and Regnier (1981) were examined to
      determine if laboratory tests of spatial cognition were significant predictors of
      older adults' use of their neighborhoods. The overall results show that
      laboratory-based measures of spatial cognition and subjects' knowledge of their
      neighborhoods are both significant predictors of their use of neighborhood goods
      and services. The ability to learn and remember the location and orientation of
      objects, when contextual cues were not provided at test, was more predictive of
      the participants' neighborhood use than either the participants' number of years
      in the neighborhood or their mobility. Spatial memory as measured by the
      Educational Testing Service Building Memory task predicted neighborhood
      knowledge, which was predictive of neighborhood use.

PMID- 1388860
TI  - Communicative function in patients with questionable Alzheimer's disease.
AB  - The communicative skills of patients with questionable Alzheimer's disease (AD)
      were examined by having patients describe events shown in a silent video cartoon.
      As anticipated, questionable AD patients provided fewer clauses in their
      descriptions than did education- and age-matched controls. This finding was
      independent of differences in word finding ability. More important, the patients
      failed to describe as many of the thematically important events as did the
      controls, a difference that affected the overall informativeness of the
      communication. Even though the patients were sensitive to event importance, there
      was no evidence of compensation in their descriptions (i.e., a greater
      concentration of important events). Several interpretations are presented that
      focus on possible deficits in the pragmatic or semantic systems of language or
      both as an early symptom of Alzheimer's disease.

PMID- 1388861
TI  - Implicit processing in the cued recall of young and old adults.
AB  - Two cued recall experiments were reported in which younger and older subjects
      studied target words varying in number of preexperimental associates. In
      Experiment 1, targets were studied in either the absence or presence of meaning
      related context cues, with recall always prompted by the cues. In the absence of
      context, words with smaller sets of associates were easier to recall than those
      with larger sets, but this effect was reduced for older subjects. The presence of
      a study context cue facilitated recall and eliminated the effect of associative
      set size for both ages. In Experiment 2, targets were studied and tested in the
      presence of unrelated words. In this situation, words with smaller sets of
      associates were less likely to be recalled than words with larger sets; again the
      effect was reduced for older subjects. The results are interpreted as an age
      decrement in processing implicitly activated information.

PMID- 1388862
TI  - The dependency-support script in institutions: generalization to community
      settings.
AB  - This study tested the generalizability of the dependency-support script, a
      behavioral system describing and explaining dependent behaviors of the
      institutionalized elderly. A comparative study with 22 community-dwelling elderly
      was conducted, which identified typical interaction patterns between the elderly
      and family members or home health nurses. The dominant interaction pattern in the
      community setting, too, was the dependency-support script. In addition, however,
      a significant social response to independent self-care behavior was observed,
      which created a highly ambivalent response contingency. Independent behaviors
      were followed about twice as often by an incongruent (dependence-supportive) than
      by a congruent (independence-supportive) response. Expectations of incompetence
      and of the helping role are offered as explanations.

PMID- 1388863
TI  - Progressive and imaginal relaxation training for elderly persons with subjective
      anxiety.
AB  - Elders exposed to either progressive or imaginal relaxation procedures reported
      significant relaxation effects and showed improvement on measures of personal
      functioning. The results of the Physical Assessment Scale of the Relaxation
      Inventory indicated that relaxation responses were acquired within and across
      sessions. Large, consistent changes in relaxation occurred in all 4 sessions. The
      Symptom Checklist-90-R, which measures self-reported personal adjustment, showed
      significant positive changes following relaxation training and at 1-month follow
      up. Elders who imagined muscle tension release profited as much as those engaged
      in actual muscle tension-release activities. This finding is of importance for
      older adults who may experience physical limitations that contraindicate muscle
      tension-release procedures.

PMID- 1388865
TI  - Adult age differences in memory for routes: effects of instruction and spatial
      diagram.
AB  - Free-recall and multiple-choice measures of memory for landmarks, sequential
      order, turns, and route configurations were obtained from younger and older
      adults after they viewed slides of 2 overlapping routes. Instructions focused
      attention on either the contents of the slides or on the course of the path; a
      control condition provided no orientational instructions. Half the subjects
      viewed maplike diagrams of the joint spatial configuration. Age interacted with
      instruction only for multiple-choice tests of landmark memory. Age interacted
      with diagram for each of the other 3 route memory components, although the
      generality of this interaction across instruction condition depended on whether
      free-recall or multiple-choice tests were used. The results suggest that route
      memory may involve both scene and layout representation, which may be
      differentially sensitive to age and presentational variables.

PMID- 1388864
TI  - Skill learning in the elderly: diminished implicit and explicit memory for a
      motor sequence.
AB  - Explicit and implicit memory for a cognitive-motor sequence was studied in
      elderly and young adults. Implicit memory was examined in a serial reaction-time
      paradigm in which sequences of hand postures repeated cyclically, then shifted to
      random sequences. Two control groups received random sequences throughout.
      Movement times (MTs) across the first 4 blocks did not improve more in the
      elderly-repeated than in the elderly-random group. In contrast, the young
      repeated group showed greater improvement in MT across these blocks than the
      young-random group. MT was less affected in the elderly than in the young by
      shifts between repeated and random sequences, indicating impaired implicit
      memory. Explicit memory, which was assessed by free recall and cued recall, also
      was impaired in the elderly. Diminished implicit memory in the elderly could not
      be explained solely by the possible intrusion of conscious recollection
      strategies.

PMID- 1388866
TI  - Age differences in using source-relevant cues.
AB  - Subjects heard words originating from 2 speakers and later decided which of the 2
      speakers said the words. Older adults had difficulty with source monitoring when
      perceptual cues from 2 sources were similar (2 female speakers), but this
      difficulty was overcome when perceptual cues were distinctive (a male and a
      female speaker) and were the only salient cues to source. Older adults also
      benefited from distinctive spatial cues when these were the only salient cues to
      source. Older adults, however, experienced difficulties in using multiple cues
      (both perceptual and spatial) to source effectively, whereas younger adults were
      able to use multiple cues to enhance their source-monitoring performance. It is
      suggested that age differences in source monitoring result from differential cue
      utilization.

PMID- 1388867
TI  - Aging and shifts of visual spatial attention.
AB  - Three experiments examined adult age differences in the efficiency of endogenous
      (voluntary) and exogenous (involuntary) attention shifts. Younger and older
      subjects performed a spatial cuing task in which abruptly onset peripheral cues
      (Experiment 1) or central, symbolic cues (Experiments 2 and 3) were presented
      before a target stimulus at intervals ranging from 50 to 250 ms. With peripheral
      cues, the magnitude of cuing effects was at least as great for older as for
      younger adults and followed a similar time course. Similar results were obtained
      with symbolic cues, although cuing effects for older adults varied with cue
      difficulty. The results suggest that cue encoding may decline with advancing age
      but that the efficiency of the shift process is preserved.

PMID- 1388868
TI  - Exercise adherence or maintenance among older adults: 1-year follow-up study.
AB  - Follow-up evaluation was conducted of 101 older men and women (mean age = 67 +/-
      5 years) who had participated in a randomized study of physiological and
      psychological effects of aerobic exercise. Eighty-five subjects completed the
      follow-up evaluation, and almost all of them (94%) reported continuing with
      physical activity, as assessed by a self-report measure. Total energy expenditure
      was calculated as an indicator of exercise maintenance, and energy expenditure at
      follow-up was predicted from measures of physiological functioning, psychological
      well-being, and cognitive functioning obtained at the conclusion of the
      structured exercise program. Greater cardiorespiratory endurance, faster
      psychomotor speed, and lower anxiety predicted exercise behavior at follow-up,
      accounting for 13% of the variance in exercise behavior. Gender was not a
      significant predictor of exercise behavior.

PMID- 1388869
TI  - Age-related deficits in prospective memory: the influence of task complexity.
AB  - Younger and older subjects were asked to perform an action whenever target words
      occurred during a short-term memory task. The difficulty of this prospective
      memory task was manipulated by varying the delay preceding the occurrence of a
      target event and by varying the number of different target events. Age-related
      performance differences emerged when there were several different target events
      but not when there was one target event presented several times. Age-related
      performance differences, when they occurred, were associated with poorer
      retrospective memory for the target events. The results were interpreted in terms
      of a componential analysis of prospective memory, which assumes both similarities
      and differences between prospective and retrospective memory.

PMID- 1388870
TI  - Age and forgetfulness: perceivers' impressions of targets' capability.
AB  - In a person perception paradigm, 72 young and 72 old adult Ss listened to tape
      recordings of a nonforgetful, moderately forgetful, or highly forgetful female
      target person being interviewed for a volunteer job. Ss then rated their opinion
      of the target's memory and how likely they would be to assign the target to easy
      and difficult tasks. Overall, Ss gave higher memory opinion ratings to old than
      to young targets. As expected, they were more likely to assign tasks to
      nonforgetful than to forgetful targets. However, they were more egalitarian than
      was hypothesized in their task assignment ratings for forgetful young versus
      forgetful old targets.

PMID- 1388871
TI  - The apprehensive respondent: failing to rate future life satisfaction in older
      adults.
AB  - Rating scales relating to the individual's past, present, and future were
      administered to subjects aged 60 to 90; those who completed all ratings (N = 589)
      were compared with others who specifically failed to rate the future (N = 150).
      The groups were differentiated by age, gender, health, and marital status. Total
      subjective well-being did not differ, but specific subjective well-being factors
      concerning time and aging could serve as discriminators. These differences
      suggest that these older adults might be apprehensive about their future, and
      that skipping future-related questions is a genuine reaction with both
      psychological and methodological implications.

PMID- 1388872
TI  - As the second decade of AIDS begins: an international perspective on the ethics
      of the epidemic.

PMID- 1388874
TI  - Subcellular localization of recombinant truncated Gag precursor proteins of HIV
      expressed in Saccharomyces cerevisiae.
AB  - OBJECTIVE: To determine signals contained in the HIV-1 Gag precursor implicated
      in protein transport. DESIGN: To study the localization of truncated Gag proteins
      expressed in Saccharomyces cerevisiae. METHODS: Thin-section immunoelectron
      microscopy studies were performed on S. cerevisiae cells producing myristoylated
      or non-myristoylated Pr55gag, the core protein (p24) and several truncated Gag
      proteins. RESULTS: Pr55gag and the carboxy-terminal truncated Gag proteins were
      myristoylated and localized at the plasma membrane. p24 was localized in the
      nucleus or perinuclear membrane. However, addition of a myristoyl group to p24
      targeted this molecule to the plasma membrane. CONCLUSIONS: The myristoylated
      amino-terminal 214 amino acids are sufficient to target Pr55gag to the plasma
      membrane. Subcellular signals implicated in protein transport are present in the
      core p24 polypeptide which may become dominant or accessible in the absence of
      the amino-myristoyl group.

PMID- 1388873
TI  - HIV-1 gp41 contains two sites for interaction with several proteins on the helper
      T-lymphoid cell line, H9.
AB  - OBJECTIVE: To characterize putative binding sites for HIV-1 gp41 to H9 cells.
      DESIGN: Based on accumulating evidence in the literature that HIV-1 can bind to
      cell surfaces independent of CD4, we attempted to clarify whether gp41, the
      transmembrane HIV-1 protein, contributes to CD4-independent binding. We therefore
      tested binding of gp41 to cells. METHODS: Using fluorescence-activated cell
      sorter analysis, we examined the binding of recombinant gp160 (gp160) and soluble
      gp41 (sgp41; Env amino acids 539-684) to H9 cells, and located the putative
      binding site(s) of gp41 by inhibition using 16 HIV-1 Env peptides. Putative HIV-1
      receptor proteins in H9 cell lysates were Western blotted and precipitated using
      sgp41. RESULTS: sgp41 bound to the CD4+ H9 cells and rgp160 bound to H9 cells
      independent of gp120-binding sites on CD4 molecules. Two gp41 peptides (Env amino
      acids 591-605 and 651-665) inhibited the binding of sgp41 to H9 cells. Four
      bands, of 37, 40, 55 and 97 kD, were blotted in H9 cell lysates, and three bands,
      40, 97 and 108 kD, were observed in the precipitation analysis using lysates of
      125I-surface-labelled H9 cells and sgp41 attached to sepharose beads.
      CONCLUSIONS: HIV-1 gp41 contains two putative binding sites to H9 cells. These
      sites may be located within Env amino acids 591-605 (ERYLKDQQLLGIWGC) and 651-665
      (TLLEESQNQQEKNEQ). Using two different techniques, five proteins (37, 40, 55, 97
      and 108 kD) were identified in H9 lysates as possible candidates for gp41
      binding.

PMID- 1388875
TI  - Design of polymerase chain reaction primers for the selective amplification of
      HIV-1 RNA in the presence of HIV-1 DNA.
AB  - OBJECTIVE: To develop a sensitive method for the specific detection of HIV-1 RNA.
      DESIGN: Following reverse transcription, the presence of HIV-1 RNA can be
      detected by polymerase chain reaction (PCR) amplification. Since specific
      detection of HIV-1 RNA may be complicated by contamination with minute quantities
      of HIV-1 DNA, samples are treated with deoxyribonuclease (DNase) prior to
      analysis. This additional step increases the possibility of RNA degradation and
      sample contamination. METHODS: A primer, HG141, was designed to hybridize to the
      poly(A) tract present in HIV-1 genomic and all HIV-1 messenger (m) RNA with its
      5' end and to the region upstream of the poly(A) tract with its 3' end. The
      increased stability of the HG141 primer/HIV-1 RNA or complementary (c) DNA
      complex, enabled PCR amplification to be performed with HG141 and the return
      primer HG62 at an annealing temperature above the melting temperature (Tm) of the
      primer-HIV-1 DNA complex. RESULTS: After reverse transcription of samples
      obtained from HIV-1-infected H9 cells, HG62/141-primed PCR amplification
      specifically detected HIV-1 RNA sequences without the need for DNAase pre
      treatment. This technique was more sensitive for the detection of HIV-1 RNA than
      SK38/39-primed PCR amplification of DNase-treated samples. CONCLUSIONS: Since the
      presence of HIV-1 RNA is indicative of HIV-1 replication for the presence of HIV
      1 virions, the RNA-specific primer described should facilitate the assessment of
      HIV-1 replication and the plasma HIV-1 viral load in HIV-1-infected individuals.
      This should prove useful in the evaluation of the effects of therapeutic
      interventions on HIV-1 infection.

PMID- 1388876
TI  - Gastrointestinal tissue cultures for HIV in HIV-infected/AIDS patients. The
      University of Calgary Gastrointestinal/HIV Study Group.
AB  - OBJECTIVE: To determine the prevalence of HIV in endoscopic biopsies from the
      esophagus, stomach, duodenum, and rectum of homosexual and bisexual men at
      various stages of HIV infection as part of a comprehensive study of
      gastrointestinal dysfunction in HIV infection. METHODS: After repeated washings
      and mechanical disruption, biopsies obtained from 58 volunteers were individually
      cocultured with pooled peripheral blood lymphocytes from healthy HIV-seronegative
      blood donors. RESULTS: HIV was isolated from at least one site in 40 out of 49
      patients. Esophageal biopsies were most frequently found positive (46%), followed
      by duodenal biopsies (44%), rectal biopsies (43%), and gastric biopsies (27%).
      Recovery of HIV was not related to any gastrointestinal signs or symptoms. HIV
      was recovered in the biopsies both from asymptomatic patients with CD4 lymphocyte
      counts greater than 500 x 10(6)/l and also from patients with more advanced
      disease receiving zidovudine therapy. CONCLUSIONS: The entire gastrointestinal
      tract appears to be a target site throughout the course of HIV infection in
      homosexual and bisexual men.

PMID- 1388877
TI  - Osteomyelitis caused by Mycobacterium haemophilum: successful therapy in two
      patients with AIDS.
AB  - OBJECTIVE: Difficulties involved in diagnosis and response to antimicrobial
      therapy are described in detail for two cases of biopsy-proven osteomyelitis
      caused by Mycobacterium haemophilum in AIDS patients. SETTING: Two large, private
      teaching hospitals in New York City, New York, USA. PATIENTS, PARTICIPANTS: A 31
      year-old woman with previous diagnoses of candida esophagitis and peripheral
      neuropathy (patient 1), and a 37-year-old man with Kaposi's sarcoma (patient 2).
      INTERVENTIONS: One patient was treated with a combination of rifampin,
      ethambutol, clofazimine, and ciprofloxacin, while the other received rifampin,
      ciprofloxacin and doxycycline. Both patients also received a short course of
      intravenous amikacin. MAIN OUTCOME MEASURES: Disease activity was monitored
      clinically by observing resolution of skin ulcers, lymphadenopathy, and pain and
      swelling in areas affected by osteomyelitis. RESULTS: Both patients experienced
      complete resolution of signs and symptoms of M. haemophilum infection. Patient 1
      was treated for 17 months and remains well after 10 months without therapy.
      Patient 2 shows no evidence of infection after 14 months of therapy. CONCLUSIONS:
      M. haemophilum infection must be considered in the differential diagnosis of
      osteomyelitis in AIDS patients, although specialized culture techniques are
      required to isolate and identify this pathogen. Excellent clinical response can
      be achieved with oral antimicrobial therapy.

PMID- 1388879
TI  - Hepatitis B antibodies in HIV-infected homosexual men are associated with more
      rapid progression to AIDS.
AB  - OBJECTIVE: To study the influence of previous or present hepatitis B virus (HBV)
      infection on HIV disease progression. DESIGN: A prospective study of HIV-positive
      individuals from HIV diagnosis to diagnosis of AIDS or to the end of the follow
      up period on 1 January 1991. Mean follow-up time was 62 months. SETTING: The
      study population was recruited from a primary health-care clinic for homosexual
      men and followed by linkage to the National AIDS Registry. PATIENTS,
      PARTICIPANTS: Of 876 individuals who were tested for HIV, 80 were HIV-positive
      and included for study. Two individuals were lost to follow-up. MAIN OUTCOME
      MEASURES: Differences in progression rates to AIDS according to HBV status at
      study entry. RESULTS: The adjusted relative risk of progression to AIDS for the
      48 subjects who were HBV-antibody-positive at study entry was 3.6 [95% confidence
      interval (CI), 1.3-10.1]. A high frequency of receptive anal intercourse was also
      associated with more rapid HIV disease progression; adjusted relative risk 2.6
      (95% CI, 1.1-5.9). CONCLUSIONS: Our results suggest that presence of HBV
      antibodies is associated with more rapid HIV-disease progression.

PMID- 1388878
TI  - Low-dose oral natural human interferon-alpha in 29 patients with HIV-1 infection:
      a double-blind, randomized, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate clinical efficacy and toxicity of low-dose oral natural
      human interferon-alpha (nHuIFN alpha) on CD4+ lymphocyte counts and clinical
      symptoms in patients with HIV-1 infection. DESIGN: Double-blind, randomized,
      placebo-controlled trial with crossover. SETTING: Private practice specializing
      in the treatment of patients with AIDS. PATIENTS, PARTICIPANTS: Only patients
      with HIV-1 infection and CD4+ lymphocyte counts between 200 and 500 x 10(6)/l
      were included for study. Thirty out of thirty-one patients at study entry
      completed treatment with placebo, and 29 completed nHuIFN alpha treatment. Mean
      patient age was 36 years (range, 25-58 years). The 30 patients included 26 men,
      of whom 22 were homosexual, and four women; five were drug users and none were
      currently on zidovudine therapy, although three had been previously.
      INTERVENTIONS: Patients were randomly assigned to cohorts of 10 to receive either
      200 IU nHuIFN alpha once daily orally absorbed or placebo with crossover after 6
      weeks. MAIN OUTCOME MEASURES: Every 2 weeks, a detailed history, physical
      examination, and laboratory tests, including CD4+ and CD8+ lymphocyte counts,
      were conducted. RESULTS: There was only a slight, transient increase in mean CD4+
      lymphocyte counts after 4 weeks of treatment with nHuIFN alpha, compared with a
      slight decline when placebo was administered. This effect reached statistical
      significance in a subgroup of patients only and was not sustained after 6 weeks.
      There were no significant changes in weight and clinical symptoms. All patients
      remained HIV-1-antibody-positive. Treatment-related adverse reactions were not
      observed. CONCLUSIONS: Our double-blind, randomized, placebo-controlled clinical
      trial did not confirm a previous report of efficiency of oral nHuIFN alpha.
      Although non-toxic, our data do not justify the widespread use of low-dose oral
      nHuIFN alpha in HIV-infected patients outside controlled clinical trials.

PMID- 1388880
TI  - Seven years of recurrent severe strongyloidiasis in an HTLV-I-infected man who
      developed adult T-cell leukaemia.
AB  - OBJECTIVE: Human T-cell leukaemia/lymphoma virus type I (HTLV-I) is endemic in
      Japan, the Caribbean basin and Africa, where it has been aetiologically linked to
      certain chronic myelopathies and adult T-cell leukamia (ATL). We sought to
      investigate whether strongyloidiasis, a parasitic disease common in these areas,
      might be a cofactor in the pathogenesis of ATL, as some reports have suggested.
      PATIENTS, PARTICIPANTS: One 35-year-old HTLV-I-seropositive French West Indian
      man with a 7-year history of recurrent strongyloidiasis associated with episodic
      hyperinfestation presenting at the Centre Hospitalier Intercommunal, Villeneuve
      St Georges, France. INTERVENTIONS: Treatment with various chemotherapeutic agents
      and symptomatic therapy for hypercalcaemia and antiviral therapy (zidovudine and
      interferon). RESULTS: The patient developed ATL and died shortly after, despite
      chemotherapy. Immunological and virological studies performed during the last 15
      months of his life showed an increase of the percentage of peripheral ATL cells,
      and progression from a polyclonal to a monoclonal integration of HTLV-I proviral
      DNA in the peripheral blood mononuclear and lymph-node cells. CONCLUSIONS:
      Recurrent strongyloidiasis appears to have been a possible cofactor associated
      with progression from healthy carrier state to ATL in our patient.

PMID- 1388881
TI  - Changing patterns in reported sexual practices in the population: multiple
      partners and condom use.
AB  - OBJECTIVE: To determine whether the pattern of change with regard to condom use
      and multiple sexual partners is influenced by gender or educational level.
      DESIGN: Findings from data collected from 1987 to 1990 about changes in condom
      use and multiple-partner activities are presented, based on telephone interviews
      with 9416 participants aged 18 to 44 years resident in central Scotland, UK.
      METHODS: Change in patterns over time were modelled in a multivariate logistic
      regression using a linear interactive modelling program. RESULTS: Several models
      showing changes in the proportion of multiple-partner respondents and condom
      users yielded a complicated pattern of behavioural change in educational status
      and gender. CONCLUSIONS: There is a large difference in reported condom use and
      multiple sexual partners by gender, but the difference is decreasing over time.
      Better educated respondents increased their use of condoms while less educated
      respondents showed a decrease in the proportion of multiple partners.

PMID- 1388883
TI  - Pentamidine-induced renal magnesium wasting.

PMID- 1388882
TI  - Serological evidence of successive HIV-2 and HIV-1 infections in a bisexual man.

PMID- 1388884
TI  - Hematuria associated with pentamidine therapy for Pneumocystis carinii pneumonia.

PMID- 1388885
TI  - Condom use and high-risk sexual practices of female prostitutes in Italy.

PMID- 1388886
TI  - Cognitive impairment of HIV infection.

PMID- 1388887
TI  - Mucosal candidiasis caused by non-albicans species of Candida in HIV-positive
      patients.

PMID- 1388888
TI  - Murine AIDS--rectal and other modes of transmission.

PMID- 1388889
TI  - Tuberculosis in HIV-infected subjects in Italy: a multicentre study. The Gruppo
      Italiano di Studio Tubercolosi e AIDS.
AB  - OBJECTIVES: To evaluate the strength of the association between tuberculosis and
      HIV infection in Italy, to assess the pattern of this association in relation to
      HIV transmission categories, and to describe clinical presentation of
      tuberculosis in a large group of Italian HIV-infected subjects. DESIGN:
      Multicentre review of clinical records. SETTING: Twenty-one infectious disease
      hospital units in nine of the 20 administrative regions of Italy. PATIENTS,
      PARTICIPANTS: All HIV-infected adults observed by each participating unit (in-
      and outpatients) between 1985 and 1989. MAIN OUTCOME MEASURE: Culture-proven
      tuberculosis. RESULTS: A total of 306 cases of tuberculosis were observed. Of
      these, 85 were pulmonary, 167 extrapulmonary, and 54 both pulmonary and
      extrapulmonary. The proportion of HIV-infected subjects diagnosed with
      tuberculosis increased during the study period from three out of 1380 (0.2%) in
      1985 to 152 out of 6504 subjects (2.3%) in 1989 (P less than 0.0001). Two hundred
      and twenty-six of the 2760 (8.19%) patients with AIDS had tuberculosis within 12
      months of AIDS diagnosis; the proportion of AIDS patients with tuberculosis
      remained stable after 1985. Compared with AIDS patients who were intravenous drug
      users, only homosexual AIDS patients had a significantly lower proportion of
      tuberculosis (178 out of 1958 versus 30 out of 522; P less than 0.02).
      CONCLUSIONS: Our data show that tuberculosis is quite common among HIV-infected
      subjects in Italy, and suggest that the risk of tuberculosis in these subjects
      has not changed. There are some differences between the pattern of the
      association between tuberculosis and HIV infection in Italy, compared with other
      industrialized countries.

PMID- 1388890
TI  - The epidemiology of AIDS-associated Kaposi's sarcoma in Italy.
AB  - OBJECTIVE: To describe the epidemiology of AIDS-associated Kaposi's sarcoma (KS)
      in Italy between January 1982 and September 1991. DESIGN: To make this study
      comparable with previous research from other countries, statistical analysis of
      data from the Italian AIDS surveillance system was performed. METHODS: Odds
      ratios (OR) and 95% confidence intervals (CI) were used to examine the
      association between several characteristics of AIDS cases and the presence of KS
      as the presenting clinical manifestation of AIDS. Trends in the frequency of AIDS
      associated KS were also estimated. RESULTS: Of the 10,584 Italian AIDS cases
      reported up to September 1991, 720 (6.8%) had KS as the presenting clinical
      manifestation. In comparison with intravenous drug users (IVDU), of whom 2.6% had
      KS, homosexual or bisexual men had a nearly 10-fold higher risk of KS (OR, 10.2;
      95% CI, 8.2-12.8), homosexual men who were also IVDU a nearly fourfold increased
      risk (OR, 4.4; 95% CI, 3.0-6.6) and heterosexuals a 2.6-fold risk (95% CI, 1.7
      3.7). Men were more likely to have KS than women. The percentage of new AIDS
      cases with KS recorded each year in Italy declined from 12.0% in 1982-1986 to
      5.8% in 1990-1991, a significant relative decrease of 19.0% per year (95% CI,
      14.1-23.6%). The decline was observed among both IVDU (20% per year) and
      homosexual or bisexual men (11.4% per year). The frequency of KS was similar
      across age groups within each transmission category, whereas geographical
      differences emerged in the prevalence of AIDS-associated KS, especially among
      IVDU. CONCLUSIONS: Our data on the epidemiology of AIDS-associated KS in Italy
      are similar to reports from North America and Europe, which show that KS is more
      common among individuals who acquired HIV infection by sexual transmission rather
      than parenterally, and that the incidence of this neoplasm is declining over
      time. The still poorly understood aetiology of AIDS-associated KS needs to be
      investigated further.

PMID- 1388891
TI  - Situational factors and thought processes associated with unprotected intercourse
      in young gay men.
AB  - OBJECTIVES: To investigate (1) the types of justifications, if any, that young
      gay men give themselves at the time they make the decision to have unprotected
      anal intercourse and (2) the types of occasion on which they are most at risk of
      having unprotected intercourse. DESIGN AND METHODS: In structured interviews, gay
      men aged 15-21 years were asked to recall two sexual encounters from the
      preceding 6 months: one in which they had had unprotected anal intercourse
      ('unsafe' encounter) and one in which they had resisted a strong temptation to
      have unprotected intercourse ('safe' encounter). We studied both types of
      encounter to enable identification of situational variables distinguishing
      between them. RESULTS: The first two factors that emerged from a Factor Analysis
      of the self-justification data ('unsafe' encounter, n = 219) involved,
      respectively, high-risk behaviour in response to a negative mood state and
      inferring from perceptible characteristics that the partner was unlikely to be
      infected. The most commonly reported self-justification was of this latter type.
      In respondents recalling both encounters (n = 115), sexual desires, mood,
      communication, and use of 'dirty talk' distinguished between the encounters. In
      contrast, type of partner, consumption of alcohol or drugs, desire for
      excitement, and use of pornography did not. CONCLUSIONS: Results are discussed in
      relation to those obtained in our earlier study of older gay men. Young gay men
      appear to be more single-minded about what they want to do sexually, and more
      likely to infer from perceptible characteristics that their partner is unlikely
      to be infected. In young gay men, a negative mood state is associated with unsafe
      sex, an opposite finding to that obtained with older gay men. The results also
      suggest the possible importance of failure to communicate about desires
      concerning safe sex and the use of 'dirty talk'; these may help to facilitate the
      occurrence of unsafe sex.

PMID- 1388892
TI  - Two methods for assessing the risk-factor composition of the HIV-1 epidemic in
      heterosexual women: southeast England, 1988-1991.
AB  - OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast
      England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS:
      First, district neonatal seroprevalence was compared on a geographical basis to
      social and demographic variables reflecting risk-factor prevalence. Second, over
      the same period eight children who developed AIDS within the first 12 months of
      life were born. RESULTS: The differences in seroprevalence between districts
      could be explained by the proportion of livebirths to women born in parts of
      Africa. An estimated 92% of neonatal seropositives could be associated with this
      demographic variable. The proportions of livebirths to women born in other
      countries, the prevalence of notified injecting drug use, and area measures of
      social deprivation, were only poorly related to HIV seroprevalence, and had no
      additional explanatory value. Seven of the eight (87.5%) children who developed
      AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both
      methods suggest that a high proportion of heterosexually transmitted HIV in
      southeast England has been imported.

PMID- 1388893
TI  - Coping with death anxiety--trying to make sense of it all?

PMID- 1388894
TI  - Brucellosis and HIV infection: a casual association?

PMID- 1388895
TI  - Levels of pyrimethamine in serum and penetration into brain tissue in humans.

PMID- 1388896
TI  - Invasive amoebic colitis in AIDS patients.

PMID- 1388897
TI  - Patient tolerance of nebulized pentamidine or cotrimoxazole as secondary
      prophylaxis for Pneumocystis carinii pneumonia.

PMID- 1388898
TI  - Immunological findings in African patients with pulmonary tuberculosis and HIV-2
      infection.

PMID- 1388899
TI  - Complement-mediated, antibody-dependent neutralizing titers of sera from
      asymptomatic and symptomatic HIV-infected individuals.

PMID- 1388900
TI  - In vitro HIV-primed cytotoxic T-lymphocytes from seronegative individuals.

PMID- 1388901
TI  - Complement activation decreases the ability of HIV transmembrane envelope protein
      to bind to specific antibody.

PMID- 1388902
TI  - Cellular and molecular features of HIV-associated Kaposi's sarcoma.

PMID- 1388903
TI  - Detection of HIV proviral DNA in cortex and white matter of AIDS brains by non
      isotopic polymerase chain reaction: correlation with diffuse poliodystrophy.
AB  - OBJECTIVE: (1) To determine whether detection of HIV proviral DNA sequences in
      the cerebral cortex correlates with the presence of pathological changes in this
      region, believed to contribute to the HIV-associated cognitive/motor complex. (2)
      To compare the frequency with which HIV infects cortical and subcortical regions
      of the brain. DESIGN: In vitro studies on HIV neurotoxicity suggest that HIV may
      be involved in the pathogenesis of cortical damage, recently defined as diffuse
      poliodystrophy (DPD) in AIDS. Previous detection of HIV antigen has localized HIV
      more frequently to subcortical than to cortical regions. It is not known whether
      HIV preferentially infects subcortical tissues or if viral expression varies in
      these two regions. METHODS: HIV antigen and proviral DNA sequences were detected
      in anterior frontal lobe tissues using immunohistochemistry (IHC) and the
      polymerase chain reaction (PCR), respectively. DPD was assessed by staining with
      antibodies against astrocytes (GFAP) and microglia/macrophages (HAM 56). RESULTS:
      HIV proviral DNA was detected in nine out of 15 cortical samples and in 10 out of
      15 white matter samples, whilst HIV p24 antigen was localized to the cortex in
      three out of 15 and to the white matter in seven out of 15 cases. DPD was found
      in 10 cases, although in five a different aetiology may have been involved.
      However, DPD was present in eight out of the nine cases in which HIV proviral DNA
      was detected in the cortex. CONCLUSIONS: Using a non-isotopic PCR method, HIV was
      detected in the brains of more cases than would be expected on the basis of IHC
      detection, and was present in the cortex as frequently as in the white matter.
      HIV, together with other factors, may contribute to the pathogenesis of DPD.

PMID- 1388905
TI  - Severe in vitro inhibition of erythropoiesis and transient stimulation of
      granulopoiesis after bone-marrow infection with eight different HIV-2 isolates.
AB  - OBJECTIVE: To correlate severe anaemia and frequent neutropenia in HIV-2-infected
      patients with an inhibitory effect on bone-marrow progenitors common to several
      HIV-2 isolates. DESIGN: The effects of eight HIV-2 isolates on early (BFU-E) and
      late (CFU-E) erythroid progenitors and on granulomonocytic (CFU-GM) progenitors,
      produced in long-term bone-marrow cultures (LTBMC), were studied. METHODS:
      Absolute numbers of BFU-E, CFU-E and CFU-GM per culture flask were calculated
      weekly for each HIV-2-infected LTBMC using semi-solid clonogenic assays, and
      compared with those obtained in mock-infected LTBMC. Levels of significance for
      comparisons were determined by an analysis of variance (ANOVA). RESULTS: Pooled
      data from 24 series of LTBMC (three series for each HIV-2 isolate) revealed 80
      and 100% inhibition of BFU-E and CFU-E on days 6 and 12 of LTBMC, respectively,
      while transient stimulation of CFU-GM was observed between days 14 and 20 of
      LTBMC, followed by total inhibition on day 30. CONCLUSIONS: These results confirm
      a direct inhibitory effect of HIV-2 on in vitro haematopoiesis. The similar
      pattern of erythroid progenitor inhibition obtained from seven out of eight
      isolates suggests that the inhibitory effect on erythropoiesis is a feature
      common to a large number of HIV-2 isolates, which correlates with clinical
      findings.

PMID- 1388904
TI  - Autoantibodies typical of non-organ-specific autoimmune diseases in HIV
      seropositive patients.
AB  - OBJECTIVE: To analyse serological aspects of systemic autoimmunity in HIV-1
      seropositive patients and in individuals at risk for AIDS. DESIGN AND METHODS:
      The reactivity of antibodies in the serum of 100 HIV-1-seropositive patients was
      investigated by enzyme-linked immunosorbent assay (ELISA) using a series of
      antigens known to be recognized by antibodies from patients with multisystemic
      autoimmune diseases, such as systemic lupus erythematosus, mixed-connective
      tissue disease and Sjogren's syndrome. RESULTS: High levels of immunoglobulin G
      (IgG) antibodies reacting with double-stranded DNA (dsDNA), synthetic peptides of
      ubiquitinated histone H2A, Sm-D antigen, U1-A RNP antigen and 60 kD SSA/Ro
      antigen were found in 44-95% of HIV-infected patients. Among histone antibodies,
      the most frequent reactions were towards the carboxy-terminal region of histone
      H1 and to histone H2B and its amino-terminal domain 1-25. Eight HIV-1
      seropositive patients at different stages of disease according to the Centers for
      Disease Control classification were also studied. In most cases, no obvious
      fluctuations were observed over several years. Antibodies were found early, and
      their specificity and apparent level of activity remained relatively constant.
      There was no evidence of such an autoimmune response in the serum of high-risk
      homosexual seronegative men. CONCLUSIONS: Although the aetiology of AIDS is
      known, in general the aetiology of multisystemic autoimmune diseases remains to
      be determined, and the sequence of events taking place remains obscure in both
      cases. It is possible that the large spectrum of antibodies found in HIV-infected
      patients reflects a specific stimulation of B-cells by nuclear antigens released
      by apoptosis during an early stage of disease.

PMID- 1388907
TI  - Detection of HIV antibodies in saliva as a tool for epidemiological studies.
AB  - OBJECTIVE: To evaluate the use of saliva specimens for the detection of HIV
      antibodies among high-risk groups in epidemiological studies. DESIGN: Testing of
      saliva specimens collected by different methods from individuals with known HIV
      status. The most reliable method was examined for its usefulness in a field study
      among a high-risk group. METHODS: Saliva samples were obtained either by using a
      cotton-wool roll ('Salivette') or as 'whole saliva'. HIV antibodies were
      determined using commercial enzyme-linked immunosorbent assays (ELISA).
      Confirmation was performed using a line immunoassay or an immunoblot assay.
      RESULTS: In 'Salivette' samples, HIV antibodies were detected by ELISA in seven
      out of 22 seropositive individuals. In contrast, testing of 'whole saliva'
      samples from 79 HIV-seropositive and 115 HIV-seronegative individuals resulted in
      a 100% correlation with HIV serum status. The positive reaction of 20 'whole
      saliva' specimens was confirmed in a line immunoassay, whereas in an immunoblot
      assay only seven specimens were positive, one negative, and 12 indeterminate. In
      an HIV prevalence study among drug users, 395 'whole saliva' samples were tested
      in two different ELISA. Both assays showed complete agreement in detecting 58
      positive and 337 negative samples. All positive samples were confirmed by the
      line immunoassay. CONCLUSION: Our study demonstrates that 'whole saliva'
      specimens are a good alternative to blood samples in epidemiological studies of
      HIV prevalence in high-risk groups.

PMID- 1388906
TI  - Identification of HIV-1 in semen following primary HIV-1 infection.
AB  - OBJECTIVE: To determine whether HIV could be identified in semen samples during
      the first few weeks after infection. DESIGN: A series of three homosexual men
      with symptomatic primary HIV-1 infection. METHODS: Each subject provided a series
      of semen samples that was examined for HIV-1 by virus culture, polymerase chain
      reaction (PCR) and transmission electron micrography. RESULTS: The first samples
      obtained for each subject (17, 22 and 24 days following onset of primary HIV-1
      infection) were all positive by PCR and negative by viral culture. Of 13 samples
      obtained during the first 80 days after onset of primary HIV-1 infection and
      analysed by PCR, 10 were positive. Only one of these samples was virus culture
      positive. Four semen samples obtained from two subjects during treatment with
      zidovudine were PCR-positive. Eight samples were examined for presence of HIV-1
      by electron microscopy and one was found to be positive. CONCLUSIONS: These
      results indicate that men with HIV-1 infection are potentially infectious through
      sexual transmission during the first few weeks after infection. The findings
      emphasize that individuals in all stages of HIV-1 infection should practise safer
      sex to reduce transmission of HIV-1.

PMID- 1388908
TI  - False-positive HIV antigens related to emergence of a 25-30 kD protein detected
      in organ recipients.
AB  - OBJECTIVE: The routine screening of organ donors for HIV-1 since 1985 has
      markedly reduced the risk of acquiring infection in organ recipients. However,
      commercial HIV-1 p24-antigen assays reveal false-positive reactivity in certain
      recipients. This observation will be discussed here. METHODS: Post
      transplantation sera collected sequentially from different organ recipients were
      tested for HIV antigen: 79 samples were from 14 kidney recipients, 57 from seven
      bone-marrow allografts and 18 from two heart recipients. Neutralization assays to
      determine specificity were performed on reactive samples. Immunoblots prepared
      from sera containing high levels of antigens were tested by Western blot using
      polyclonal anti-HIV sera. RESULTS: Abbott HIV-1-EIA kits detected non
      neutralizable antigens in early post-transplantation sera from 12 kidney, five
      bone-marrow and two heart recipients. Using in-house immunoblots prepared from
      positive non-neutralizing antigen sera, a 25-30 kD protein was detected and shown
      to be the cause of the false HIV antigen cross-reactivity. CONCLUSION: False
      positive HIV antigens related to the emergence of a 25-30 kD protein in early
      post-transplantation sera are detectable in transplant recipients.

PMID- 1388909
TI  - Zidovudine prophylaxis after accidental exposure to HIV: the Italian experience.
      The Italian Study Group on Occupational Risk of HIV Infection.
AB  - OBJECTIVES: To evaluate the use of zidovudine prophylaxis in HIV-exposed health
      care workers (HCW) in Italy and to determine its short-term toxicity. DESIGN:
      Longitudinal, open study with retrospective and prospective collection of data.
      SETTING: All Italian clinical centres that care for HIV-infected patients and are
      licensed by the Ministry of Health to dispense zidovudine and 30 hospitals
      participating in the Italian Multicentre Study on Occupational Risk of HIV
      Infection. STUDY POPULATION: HCW and other individuals who accepted zidovudine
      prophylaxis after accidental exposure to HIV. RESULTS: Data were collected for
      224 HIV-exposed individuals until 30 June 1991. An increase in zidovudine
      prophylaxis was observed. All but 10 subjects received 1000-1250 mg zidovudine
      per day. Anaemia (five cases), neutropenia (one case) and an increase in serum
      alanine aminotransferase levels (two cases) were the only haematochemical side
      effects observed; none of the subjects ceased prophylaxis because of side
      effects. More than 50% of subjects had constitutional reactions; as a result,
      prophylaxis was stopped by 29 patients. These adverse effects began within 10
      days of prophylaxis; all resolved after prophylaxis was stopped. No HIV-antibody
      seroconversions were observed after a mean follow-up of 8 months. CONCLUSIONS:
      Zidovudine prophylaxis has become a feature of the management of occupational
      exposures to HIV in health-care settings; short-term toxicity is mild, dose
      related and reversible. Further studies are needed to assess the risk of long
      term sequelae.

PMID- 1388910
TI  - High HIV seroprevalence and increased HIV-associated mortality among hospitalized
      patients with deep bacterial infections in Dar es Salaam, Tanzania.
AB  - OBJECTIVES: To correlate deep bacterial infections with HIV infection and
      evaluate the influence of HIV on clinical picture and outcome in patients with
      meningitis, pneumonia or pyomyositis. DESIGN: Case-control comparison of HIV
      seroprevalence between patients and an age- and sex-matched control group in a
      prospective cross-sectional study of hospitalized patients. PARTICIPANTS: One
      hundred and sixty-five patients admitted to hospital with either purulent
      meningitis, pneumonia or pyomyositis and 165 age- and sex-matched controls from
      orthopaedic/trauma wards. SETTING: University Hospital, Dar es Salaam, Tanzania.
      OUTCOME MEASURES: Differences in HIV seroprevalence and mortality. RESULTS: Of 78
      patients with purulent meningitis, 19 (24%) were HIV-seropositive, compared with
      13 (17%) in the control group (P = 0.345). Of 36 patients with meningitis seen
      before a meningococcal epidemic affected Dar es Salaam, there was a statistically
      significant association with HIV infection (P = 0.013). Ten out of 19 (53%) HIV
      seropositives died, compared with nine out of 59 (15%) seronegatives (P = 0.028).
      Of patients with pneumococcal meningitis, five out of six (83%) seropositives
      died, compared with two out of 12 (17%) seronegatives (P = 0.013). Fifteen out of
      45 (33%) patients with pneumonia were HIV-seropositive, compared with four (9%)
      in the control group (P = 0.001). There was no difference in mortality between
      seropositive and seronegative patients with pneumonia. HIV seroprevalence was 62%
      among 42 patients with pyomyositis and 12% among 42 controls (P less than
      0.0001). Eighteen out of 25 (72%) seropositive patients with pyomyositis
      fulfilled the World Health Organization (WHO) clinical case definition for AIDS.
      Response to recommended antibiotic treatment was satisfactory among patients with
      pneumonia and pyomyositis. CONCLUSIONS: These results show a strong association
      between pyomyositis, pneumonia and HIV infection. They also indicate an increased
      mortality associated with HIV infection in patients with pyogenic meningitis,
      especially pneumococcal meningitis. Pyomyositis should be considered an indicator
      of stage III HIV disease in the proposed WHO clinical staging system.

PMID- 1388911
TI  - HIV risk factors in three geographic strata of rural Rakai District, Uganda.
AB  - OBJECTIVES: To examine risk factors for HIV-1 infection in three geographic
      strata (main road trading centers that service local and international traffic,
      small trading villages on secondary dirt roads that serve as foci for local
      communications, and agricultural villages off main and secondary roads) in Rakai
      District, Uganda. DESIGN AND METHODS: Serological, sociodemographic,
      knowledge/behaviors and health survey conducted in 21 randomly selected community
      clusters; complete data were collected for 1292 consenting adults. RESULTS:
      Fifteen per cent of the men and 24% of the women were HIV-1-positive. On
      univariate analysis, several sociodemographic and behavioral factors were
      significantly associated with risk of HIV infection, including age, place of
      residence, travel, occupation, marital status, number of sex partners, sex for
      money or gifts, history of sexually transmitted disease (STD), and history of
      injections. On multivariate analysis, age, residence and number of sex partners
      remained significantly associated with HIV infection in both sexes; a history of
      STD and not having been circumcised were significant in men. There was a
      significant interaction between place of residence and reported number of sex
      partners: for any given level of sexual activity, the risk of HIV infection was
      markedly increased if the background community prevalence was high. CONCLUSION:
      Sexual transmission appears to be the primary behavioral risk factor for
      infection, but the risks associated with this factor vary substantially between
      the three geographic strata. These data can be used to design targeted
      interventions.

PMID- 1388912
TI  - HIV-1 transmission through breast-milk: appraisal of risk according to duration
      of feeding.
AB  - OBJECTIVES: To estimate the risk of HIV-1 transmission through breast-milk in
      children born to infected mothers, and to determine the relationship between
      duration of breast-feeding and risk. DESIGN AND METHODS: The study population
      included 168 breast-fed and 793 bottle-fed children born to seropositive mothers.
      All subjects were enrolled and followed-up in the Italian Register for HIV
      Infection in Children; HIV sero-status was defined in all children. Multivariate
      analysis was performed using a logistic regression model. Independent variables
      included biological factors (duration of breast-feeding, gestational age,
      clinical condition of mother at delivery, mode of delivery, birth-weight and
      sex). Year of birth and age when HIV infection was diagnosed were also considered
      in the analysis attempting to control for possible selection biases. RESULTS:
      Breast-feeding increased the risk of HIV-1 transmission. The estimated adjusted
      odds ratio for 1 day of breast- versus bottle-feeding was 1.19 (95% confidence
      interval, 1.10-1.28). The infection odds ratio of breast- versus bottle-feeding
      increased with the natural logarithm of the duration of practice. CONCLUSIONS:
      These results are the first to provide an appraisal of the additional risk of HIV
      1 transmission associated with a seropositive mother breast-feeding her child.
      Biological significance of this route of transmission was supported by
      demonstration of a relationship between duration of breast-feeding and risk of
      HIV-1 transmission.

PMID- 1388913
TI  - Coping with death anxiety: help-seeking and social support among gay men with
      various HIV diagnoses.
AB  - OBJECTIVE, DESIGN AND PARTICIPANTS: We examined sources of help-seeking related
      to worries or concerns about death and dying and the effects of social support on
      death anxiety in a longitudinal sample of gay men (n = 52). RESULTS: Friends and
      primary sexual partners were the most frequent sources sought in dealing with
      death concerns for all groups of respondents (HIV-negative, HIV-positive
      asymptomatic, and HIV-positive symptomatic). Men experiencing HIV symptoms were
      more likely than HIV-negative and asymptomatic men to use formal sources of
      support (medical, psychological). Although HIV-positive symptomatic men did not
      differ from HIV-negative men in terms of help-seeking from family sources, they
      were significantly more likely to seek the help of family members than HIV
      positive asymptomatic men. All three HIV groups showed significantly different
      mean levels of death anxiety, with HIV-negative men reporting the lowest level
      and HIV-positive symptomatic men the highest. Among HIV-negative men, only mental
      health sources of support (psychologists and clergy) were significantly related
      to death anxiety, measured 1 year later (beta = -0.35). These sources of support
      were also associated with death anxiety among HIV-positive asymptomatic men, but
      in the opposite direction (beta = 0.26). Contrary to expectations, men
      experiencing HIV symptoms benefited most from family support (beta = -0.31),
      although peer (beta = -0.19) and medical (beta = -0.28) support sources were also
      prominent. CONCLUSIONS: Thus, while earlier research found peers to be the most
      common and effective source of support among gay men, this study suggests that
      obtaining support from family may become particularly important as one approaches
      death. The effectiveness of social support in reducing death anxiety appears to
      vary over the course of the disease from asymptomatic to symptomatic. HIV
      symptomatic men obtain support from a wide range of helpers, including medical
      and peer supports and family.

PMID- 1388914
TI  - Abiding memories.

PMID- 1388915
TI  - Sounding the alarm.

PMID- 1388916
TI  - Telling home truths.

PMID- 1388917
TI  - Incontinence in old age.

PMID- 1388918
TI  - Programmed to succeed.

PMID- 1388919
TI  - The demon drink.

PMID- 1388920
TI  - The Bradford Saturday Club.

PMID- 1388921
TI  - Designed for living.

PMID- 1388922
TI  - Talking point.

PMID- 1388923
TI  - Our major concerns.

PMID- 1388924
TI  - Out of pocket.

PMID- 1388925
TI  - As I was saying....

PMID- 1388927
TI  - Social disservices?

PMID- 1388926
TI  - Choice thoughts.

PMID- 1388928
TI  - Spanish eyes.

PMID- 1388929
TI  - Watch, read and learn.

PMID- 1388930
TI  - Which brain defects accompany cyclopia?
AB  - We report a fetus with an association of cyclopia without proboscis,
      aprosencephaly and agnathia. Analysing literature cases and the case presented
      here we can suggest that: 1) not only alobar holoprosencephaly but also more
      severe forebrain anomalies can be a brain equivalent of cyclopia; 2)
      aprosencephaly can be viewed as the earliest known variant of prosencephalic
      series; and 3) "agnathia-holoprosencephaly" association is etiologically
      heterogeneous.

PMID- 1388931
TI  - Laryngeal atresia sequence as part of the DiGeorge developmental field defect.
AB  - The subject of the present report is a male newborn with laryngeal atresia (LA)
      type I, giving rise to a malformation sequence consisting of overdistended
      polyalveolar lungs and nonimmune fetal hydrops with massive ascites. The infant
      was chromosomally normal and the first child of consanguineous parents. Retention
      of liquid secreted by the fetal lungs in utero was the pathogenetic mechanism,
      responsible for the LA sequence. The LA was part of a complex constellation of
      anomalies, compatible with the DiGeorge developmental field defect.

PMID- 1388932
TI  - MCA/MR syndrome in two female siblings: new entity or variant examples of Coffin
      Lowry versus Atkin-Flaitz syndromes?
AB  - We report two sisters with mental retardation, coarse facial features,
      telecanthus, flat malar region, prominent lower lip, kyphoscoliosis, and tapering
      fingers. Although these patients' phenotypes showed considerable overlap with the
      Coffin-Lowry and the Atkin-Flaitz syndromes, their overall picture makes these
      diagnoses controversial.

PMID- 1388933
TI  - Hypomelanosis of Ito and severe sensorineural deafness.
AB  - In this report we describe an 8-year-old boy of Algerian origin with profound
      sensorineural deafness and skin pigmentation anomalies consistent with the
      diagnosis of hypomelanosis of Ito. On the basis of this observation the etiologic
      heterogeneity of this condition is discussed.

PMID- 1388934
TI  - Rieger syndrome and interstitial 4q26 deletion.

PMID- 1388935
TI  - Combined 10pter-->p11 and 18pter-->q11 trisomy in a 7-year-old child.
AB  - We report a severely mentally retarded, dysmorphic girl aged 7 years with a
      47,XX, +der(18), t(10;18)(p11.2;q11.2)mat. The phenotype of our patient is
      compared with 6 cases of trisomy 10p and 10 cases of trisomy 18q- from the
      literature. The short trisomic segment 10pter-10p11 appears to affect more the
      phenotype than the trisomic segment 18qter-q11.

PMID- 1388936
TI  - Structure of 1,1-dichloro-2-(4-methoxyphenyl)-2,3-diphenylcyclopropane.
AB  - C22H18Cl2O, M(r) = 369.3, monoclinic, P2(1)/a, a = 16.585(1), b = 17.328(1), c =
      13.192(3) A, beta = 107.443(8) degrees, V = 3616.8 A3, Z = 8, Dx = 1.356 g cm-3,
      lambda(Mo K alpha) = 0.71069 A, mu = 3.2 cm-1, F(000) = 1536, T = 138 K, R =
      0.039 for 5450 observed reflections. The structural features of the two
      independent molecules are quite similar except in the orientation of the methoxy
      group. The cyclopropane ring shows the expected bond-length asymmetry with C(2)
      C(3) as the longest bond. The two cis-arranged phenyl rings adopt similar
      conformations as observed in diaryl-cyclopropanes, with one ring in the bisecting
      position and the other near the perpendicular position. The conformation of the
      third aryl ring is also near the perpendicular position. The overall conformation
      of the three aryl rings is different from the helical propeller conformation
      consistently observed in tamoxifen and all other known tri(tetra)aryl-vinyl
      systems.

PMID- 1388937
TI  - Structure of asperketal B.
AB  - 3,7,11-Trimethyl-13-oxabicyclo[8.3.0]trideca-2,6-diene-12-spiro-2' -(5',5'
      dimethyltetrahydrofuran), asperketal B, C20H30O2, M(r) = 302.46, orthorhombic,
      P2(1)2(1)2(1), a = 10.064(1), b = 22.214(2), c = 8.330 (1) A, V = 1862.3 A3, Z =
      4, Dx = 1.08 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 4.55 cm-1, F(000) =
      664, T = 294 (1) K, R = 0.031, wR = 0.027 for 953 data. The backbone of the
      molecule is composed of a cyclodecadiene ring which is cis fused to a bicyclic
      ketal system. The relative configurations at C(1), C(10), C(11) and C(12) are
      1S*, 10R*, 11R* and 12R*.

PMID- 1388938
TI  - Structure of tris(dicyclohexylphenylphosphine)gold(I) perchlorate.
AB  - [Au(P(C6H11)2(C6H5))3][ClO4], M(r) = 1119.59, trigonal, R3c, a = 13.192(5), c =
      52.83 (2) A, V = 7962 (9) A3, Z = 6, Dx = 1.401 g cm-3, lambda(Mo K alpha) =
      0.71073 A, mu = 29.5 cm-1, F(000) = 3468, T = 296 K, final R = 0.047 for 1321
      unique observed reflections. The Au atom in the anion and the perchlorate ion in
      [Au(Cy2PhP)3][ClO4] lie on a threefold axis. The complex has an almost ideal
      trigonal-planar geometry, with an Au--P distance of 2.421 (3) A, P--Au--P angles
      of 119.9 (3) degrees, and the Au atom only 0.08 (2) A out of the plane defined by
      the three P atoms.

PMID- 1388939
TI  - Structure of aqua[N,N'-ethylenebis(N-carbamoylmethylglycinato)]copper(II)
      dihydrate.
AB  - The structure consists of a copper(II) cation octahedrally coordinated to the
      polyaminocarboxylate ligand through five ligating atoms: one N atom of the
      ethylenediamine ring, two carboxylate O atoms and a molecule of water form a
      square plane, while one amide O and the other ethylenediamine-ring N atom are
      above and below the plane. The latter two atoms display tetragonal distortion.
      Eight intermolecular hydrogen bonds involve H, N and O atoms of the complex as
      well as the two water molecules of crystallization.

PMID- 1388940
TI  - Structure of calcium 2,6-difluorobenzoate dihydrate.
AB  - Ca2+.2C7H3O2F2-.2H2O, M(r) = 390.3, monoclinic, C2/c, a = 17.584 (4), b = 10.771
      (3), c = 7.887 (2) A, beta = 91.28 (2) degrees, V = 1493 A3, Z = 4, Dm = 1.75, Dx
      = 1.74 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 4.92 cm-1, F(000) = 792, T =
      293 K, final R = 0.037 for 2415 unique observed reflections. The eight-coordinate
      Ca2+ ion is linked to six carboxylate O atoms from four different 2,6
      difluorobenzoate ions and two water molecules. Each 2,6-difluorobenzoate ion
      chelates one Ca2+ ion and forms unidentate bridging linkages to two other Ca2+
      ions leading to a polymeric structure. Unlike the situation in calcium 2
      fluorobenzoate, the two F atoms in this structure are not involved in significant
      C-F...H-O hydrogen bonding.

PMID- 1388941
TI  - Structure of lansimide 2, a product from Clausena lansium.
AB  - The natural product lansimide 2 is a 1:1 mixture of two different cyclic amides,
      C18H17NO2.C18H19NO3. The mixture crystallizes as a molecular pair in the
      centrosymmetric space group P21/n. M(r) = 576.69, monoclinic, a = 20.151 (2), b =
      6.2984 (4), c = 24.051 (2) A, beta = 104.339 (8) degrees, V = 2957.4 A3, Z = 4,
      Dx = 1.30 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 6.1 cm-1, F(000) = 1224, T
      = 163 (1) K, R = 0.033, wR = 0.034 for 5002 observed reflections.

PMID- 1388942
TI  - Structure of bis(4-chlorophenolato)[hydrotris(3,5-dimethyl-1-
      pyrazolyl)borato]oxomolybdenum(V).
AB  - [Mo(C15H22BN6)(C6H4ClO)2O], M(r) = 664.24, triclinic, P1, a = 10.585 (2), b =
      12.068 (3), c = 13.728 (3) A, alpha = 88.01, beta = 69.94, gamma = 65.78 degrees,
      V = 1490.8 A3, Z = 2, Dx = 1.48 g cm-3, Mo K alpha, lambda = 0.71073 A, mu = 6.5
      cm-1, F(000) = 678, T = 296 (1) K, R = 0.034, wR = 0.049 for 4634 observed
      independent reflections with F2 greater than 3 sigma (F2). This is the second
      structurally characterized mononuclear monooxo transition-metal complex
      containing the phenolato ligand. The molecule exhibits a distorted octahedral
      coordination geometry, and the Mo atom is ligated by a terminal O atom, two p
      chloro-substituted phenolato groups, and a tridentate facially coordinated
      hydrotris(3,5-dimethylpyrazolyl)borate ligand (L).

PMID- 1388943
TI  - Structure of a protected C3-C10 subunit of erythromycin and its C8 epimer.
AB  - (1) (2S,3R,4R,6R)-3,4-O-Carbonyl-7,7-dimethylenedithio-2,4,6-trimet hylnonane
      1,3,4-triol, C15H26O4S2, M(r) = 334.49, triclinic, P1, a = 6.460 (2), b = 8.917
      (3), c = 15.616 (5) A, alpha = 83.60 (3), beta = 83.41 (2), gamma = 89.52 (2)
      degrees, V = 888.0 (5) A3, Z = 2, Dx = 1.25 g cm-3, mu = 2.980 cm-1, lambda (Mo K
      alpha) = 0.7107 A, F(000) = 360, T = 298 K, R = 0.0465 for 1832 reflections [Fo
      greater than or equal to 4 sigma (Fo)]. (2) (2S,3R,4R,6S)-3,4-O-Carbonyl-7,7
      dimethylenedithio-2,4,6-trimet hylnonane-1,3,4-triol, C15H26O4S2, M(r) = 334.49,
      monoclinic, P21, a = 8.1849 (8), b = 8.9456 (14), c = 12.0258 (14) A, beta =
      100.878 (8) degrees, V = 864.7 (2) A3, Z = 2, Dx = 1.28 g cm-3, mu = 3.060 cm-1,
      lambda (Mo K alpha) = 0.7107 A, F(000) = 360, T = 298 K, R = 0.0569 for 2001
      reflections [Fo greater than or equal to 4 sigma (Fo)]. The two diastereomers
      differ in configuration at C6. For (1) there are two unique molecules in the unit
      cell. These two molecules differ in conformation by a rotation about the bond C7
      C8. The molecules are hydrogen bonded into infinite chains along b. The hydroxyl
      O atom of molecule (2), O10', acts as both a donor and an acceptor in hydrogen
      bonding interactions with the carbonyl O atom, O14, and the hydroxyl H atom, H10,
      of molecule (1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388944
TI  - Solid-state conformations of aminosuccinyl peptides: structure of tert
      butyloxycarbonyl-L-prolyl-L-aminosuccinyl-glycyl-L-alanine methyl ester (Boc-L
      Pro-L-Asu-Gly-L-Ala-OMe). A case of pseudo-translational symmetry.
AB  - C20H30N4O8, M(r) = 454.48, monoclinic, P2(1), a = 13.411 (2), b = 12.592 (2), c =
      14.710 (1) A, beta = 104.30 (1) degrees, V = 2407 (6) A3, Z = 4, Dx = 1.254 Mg m
      3, lambda (Cu K alpha) = 1.5418 A, mu = 0.783 mm-1, F(000) = 968, room
      temperature, final R = 0.086, wR = 0.080 for 4055 observed reflections. The title
      compound is a model for the intermediate formed in the deamidation reaction of
      porcine adrenocorticotropin hormone. The structure presents a pseudo
      translational symmetry and was solved by using a modified version of the SIR88
      package. In the refinement, few stereochemical restraints were needed to handle
      the static disorder shown by the C-terminal fragment of one molecule in the
      asymmetric unit. The conformation of the two independent molecules is almost
      identical and is a II' beta-bend, stabilized by an intramolecular hydrogen bond.
      In the crystal, screw-related molecules are linked by hydrogen bonds. The two
      molecules in the independent unit are related by the translation vector u =
      0.4962 (2)a + 0.7310 (2)b + 0.5075 (2)c.

PMID- 1388945
TI  - 1,2-Naphthalenedicarboxylic acid: structures of channel clathrates and an
      unsolvated crystalline phase.
AB  - (1) 1,2-Naphthalenedicarboxylic acid-diethyl ether, C12H8O4.nC4H10O, M(r) =
      216.19, tetragonal, I4(1)/a, a = 22.086 (3), c = 9.463 (3) A, V = 4616 (2) A3, Z
      = 16, F(000) = 1792 (without ether), F(000) = 1873 (with 2.7 molecules of ether
      per unit cell), Dx = 1.24 g cm-3 (without ether), Dx = 1.31 g cm-3 (with 2.7
      molecules of ether per unit cell), lambda(Mo K alpha) = 0.71073 A, T = 296 K, mu
      = 0.88 cm-1, R = 0.052 for 1130 unique reflections having I greater than 3 sigma
      I. (2) 1,2-Naphthalenedicarboxylic acid, C12H8O4, M(r) = 216.19, triclinic, P1, a
      = 9.027 (1), b = 9.234 (1), c = 7.256 (1) A, alpha = 106.08 (1), beta = 90.79
      (1), gamma = 111.80 (1) degrees, V = 535.0 (1) A3, Z = 2, F(000) = 224, Dx = 1.34
      g cm-3, lambda (Mo K alpha) = 0.71073 A, T = 296 K, mu = 0.95 cm-1, R = 0.043 for
      1216 unique reflections having I greater than 3 sigma I. (3) 1,2
      Naphthalenedicarboxylic acid-dimethoxyethane, C12H8O4.nC4H10O2, M(r) = 216.19,
      tetragonal, I4(1)/a, a = 22.067 (2), c = 9.465 (2) A, V = 4609 (1) A3, Z = 16, Dx
      = 1.25 g cm-3 (without dimethoxyethane), Dx = 1.39 g cm-3 (with 4.4 molecules of
      dimethoxyethane per unit cell), lambda(Mo K alpha) = 0.71073 A, T = 296
      K.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388946
TI  - Clinical evaluation of Clearfil photoposterior: 3-year results.
AB  - The purpose of this study was to evaluate a new resin composite/bonding
      restorative system in clinical trials involving human subjects. Sixty
      restorations were inserted in Class I and Class II preparations in premolars and
      molars. The enamel margins of the preparations were etched for 60 seconds with
      37% phosphoric acid gel. The dentinal surfaces of cavity preparations were etched
      for 40 seconds with 37% phosphoric acid in glycerine (K-etchant gel) and bonding
      agent (Clearfil Photo Bond) applied. A resin composite (Clearfil Photoposterior)
      was placed in three increments with a 20 second light cure of each increment and
      a 60 second light cure of the final increment. All the restorations were
      evaluated using the USPHS system and M-L indirect scale. At 36 month recalls,
      compared to baseline, surface texture for essentially all the restorations was
      rated Bravo, while all other characteristics were rated Alpha. Secondary caries
      was reported for one restoration during the third year of clinical use. Wear
      showed an adjusted mean value of 14.6 microns at 36 months or 4.9 microns per
      year. No cases of clinical post-operative sensitivity to hot, cold, percussion
      and foods were reported during the length of the study. Clearfil Photoposterior
      resin composite system has exhibited remarkable wear resistance and no post
      operative sensitivity throughout the length of the study.

PMID- 1388948
TI  - Microleakage of Vitrebond/P-50 Class II restorations.
AB  - Thirty extracted human mandibular permanent first and second molars were used in
      this study. Class II preparations were made extending 1 mm below the CEJ at the
      mesial and 1 mm above the CEJ at the distal aspects. In 15 of the teeth Vitrebond
      was applied to all exposed dentin (A) while in 15 teeth the gingival floor was
      left exposed (B). After cure, the enamel margins were etched with H3PO4 gel and
      the Vitrebond surfaces were treated with Scotchbond 2. The P-50 was transferred
      to the approximal boxes and occlusal aspects in three increments, each compressed
      firmly and cured for 60 seconds. The restored teeth were stored in saline at 37
      degrees C for 1 week. The teeth were thermocycled x250 in 0.5% basic fuchsin
      between 8 degrees C and 50 degrees C with a dwell time of 15 seconds. The teeth
      were embedded in epoxy resin and five mesiodistal sections cut. Microleakage at
      the mesial and distal aspects were scored from 0 to 3 depending on the extent of
      the microleakage. The data were analyzed by the Wilcoxon 2-sample and the matched
      pair signed rank tests. Leakage above the CEJ was significantly less than below
      the CEJ and significantly reduced when Vitrebond was extended to the cavosurface
      margins.

PMID- 1388947
TI  - Moist versus dry dentin: its effect on shear bond strength.
AB  - This study compared the shear bond strengths of dentin bonding systems applied to
      air dried and blot (moist) dried dentin. Five systems with primers possessing
      hydrophilic properties were evaluated. Three contained acetone. All Bond,
      Amalgambond, Mirage Bond and Tenure all produced significant statistical
      improvement in shear bond strength values when applied to moistened dentin.
      Mirage Bond values quadrupled. Bond strength values with Gluma were compromised
      by the presence of moisture. It was concluded that acetone probably facilitated
      deeper and more complete penetration of resin into dentin to enhance micro
      mechanical retention. Amalgambond, while free of acetone is strongly hydrophilic
      and is known to form substantial mechanical bonding through the formation of a
      resin rich superficial layer of dentin (hybridization). Gluma while hydrophilic
      does not appear to possess the same behavioral characteristics embodied in the
      other systems as evidenced from lack of a bond to moist dentin.

PMID- 1388949
TI  - Shear bond strength of repaired glass ionomers.
AB  - This in vitro study investigated repairs to glass ionomer cements (GIC) with a
      new GIC layer added after different time intervals (15 minutes, 24 hours, 6 days)
      and after different types of surface treatments. The results indicated: 1) GIC
      can be repaired with a new GIC layer added on with specific types of surface
      treatment. The shear bond strength created at the interface attained no less than
      65% of the value for unrepaired specimens; 2) The surface treatment that best
      enhances the bond was either 20 seconds of etching with phosphoric acid or
      roughening the surface followed by acid etching. The latter showed higher values
      but not at a statistically significant level; 3) Both Ketac-Fil and Fuji II
      provided high bond strengths when the repair occurred on a newly set surface (15
      minutes); 4) When Ketac-Fil and Fuji II specimens were repaired at 24 hours,
      shear bond strength was lower compared to the repair bond strength at 15 minutes
      and demonstrated less cohesive ability; 5) When 6-day-old specimens were
      repaired, Fuji II provided higher bond strength values than Ketac-Fil.

PMID- 1388950
TI  - Evaluation of resins for provisional restorations.
AB  - An in vivo study of two resin materials (Barricaid and Caulk Temporary Crown and
      Bridge Resin) was done to determine the retention, post-operative sensitivity,
      and fabrication time of provisional restorations made from these materials.
      Following the placement of these resins in 67 intracoronal cavity preparations of
      19 adult patients, a baseline evaluation was made which included a clinical
      examination and color slides. Twenty-four hours after the temporary restorations
      were placed, the patients completed evaluations of the post-operative sensitivity
      experienced. There was no difference in post-operative sensitivity between the
      teeth restored with Barricaid or Caulk Temporary Crown and Bridge Resin. At the
      insertion appointment of the final restoration, the interim restoration's success
      rate was determined. There was no difference between the retention of the two
      provisional materials. Fabrication time was significantly different with
      Barricaid restorations requiring less than one-half the fabrication time of the
      Caulk Temporary Crown and Bridge Resin material.

PMID- 1388951
TI  - Relative fit of new denture resins polymerized by heat, light and microwave
      energy.
AB  - This study compared in vitro the relative fit of seven denture resins polymerized
      by different methods to their gypsum casts. Relative fit in the molar-to-molar
      region of the resin bases on their stone casts was evaluated independently by
      five evaluators at three times (after processing, after polishing and after
      storage in water) and ranked using non-parametric statistics. The denture resins
      polymerized by microwave energy, (Acron MC), low heat, (Perform, 45 degrees C),
      and visible light, (Triad) fit better after polishing and after storage in water
      than those resins polymerized at higher temperatures (Lucitone 199, 74 degrees C
      and Accelar 20, Compak and Permacryl 20, 100 degrees C). The traditional heat
      polymerized resin (Lucitone) had an average fit after storage in water.

PMID- 1388952
TI  - Comparison of a chlorhexidine rinse and a wooden interdental cleaner in reducing
      interdental gingivitis.
AB  - The purpose of this study was to evaluate the effectiveness of an antimicrobial
      rinse (chlorhexidine) compared to a positive control of mechanical oral hygiene
      in reducing interdental gingival inflammation. The mechanical group showed a
      significantly greater reduction in interdental gingivitis as determined by
      bleeding compared to the chemical rinse. Even though the chemical rinse has been
      shown to be effective in reducing inflammation on the visible buccal and lingual
      gingival surfaces, it is significantly less effective than the mechanical device
      in reducing bleeding in the interdental area.

PMID- 1388953
TI  - Effect of temporary cements on the bond strength of a resin cement.
AB  - This study evaluated the effect of temporary cements with or without eugenol on
      the bond strength of a dual-cure resin cement to dentin. Etched, silanated Dicor
      buttons were bonded to dentin surfaces after pretreatment with the cements. The
      buttons were sheared in an Instron testing machine. The results showed that shear
      bond strength is not affected by the temporary cements, if the dentin is cleaned
      with pumice and treated with Prisma Universal Bond 3 dentin bonding system.

PMID- 1388954
TI  - Sealing ability of two intermediate restorative materials in bleached teeth.
AB  - This study compared the radicular penetration of bleaching agents in
      endodontically treated teeth containing an IRM base, a Cavit base, and no base.
      Forty-five extracted human maxillary central incisors treated with conventional
      endodontic therapy with laterally condensed gutta percha and sealer were randomly
      divided into three groups: (1) Cavit base, (2) IRM base and (3) no base. In
      groups 1 and 2, a 3.5 mm thickness of base material was placed at the time of
      obturation. After storage in saline for 1 week, the teeth were bleached with a
      mixture of 35% hydrogen peroxide and sodium perborate, combined with a 10%
      methylene blue dye solution, using a combination thermocatalytic and non
      thermocatalytic bleaching technique. The apical distance of dye penetration was
      measured. The control group demonstrated dye penetration to the apex, indicating
      that a base is required to prevent leakage of bleaching agents when this
      combination of bleaching techniques is used. The mean distance of leakage was
      3.43 mm (+/- 1.14) for the Cavit group and 5.94 mm (+/- 1.72) for the IRM group.
      Analysis with a t-test revealed that Cavit was a more effective barrier to
      leakage than IRM (T = 4.20, P less than 0.001).

PMID- 1388955
TI  - Effect of axial load and temperature cycling on microleakage of resin
      restorations.
AB  - This study evaluated the microleakage of Class V resin restorations subjected to
      temperature and axial load cyclings. The preparations were made at the mesial and
      distal aspects of 29 mandibular first and second molars. The enamel margins were
      beveled, acid etched, washed and dried. Kerr XR Bonding System was applied to the
      dentin and etched enamel and Herculite composite cured in two increments. The
      teeth were stored in saline for 7 days, thermocycled x500 in 0.5% basic fuchsin
      between 8 degrees C and 50 degrees C (A); subjected to an occlusal load of 34 MPa
      in the dye without thermocycling (B); or followed by thermocycling (C). The
      leakage was scored from 0 to 4 at both the enamel and cementum aspects of the
      restorations. The data were analyzed by the Kruskal-Wallis test. The microstrain
      of five restored teeth subjected to an occlusal load of 34 MPa was measured.
      Microleakage of the mesial restorations was significantly greater at the cementum
      aspects of the restorations subjected to both temperature and occlusal loading
      when compared to the restorations subjected to temperature cycling or load
      cycling only. The microstrain in eight of the 10 restorations was significantly
      greater at the cementum aspects of the restorations than at the enamel aspects.

PMID- 1388957
TI  - Mammalian bites: risk and management.
AB  - Human and animal bites can result in bacterial infection of the wound, and may be
      associated with the transmission of viral pathogens, including blood borne
      pathogens. The management of bite injuries requires local wound care, antibiotics
      if appropriate and prophylaxis against transmission of tetanus and viral
      pathogens including Hepatitis B virus. A review of bite injuries and management
      is presented.

PMID- 1388956
TI  - Dental health care workers' response to the HIV epidemic.
AB  - Random samples of Minnesota DHCWs were surveyed in late 1989 regarding HIV
      related and infection control KAPs. Response rates were: dentists 69% (438/631);
      hygienists 73% (439/603); and assistants 56% (384/691). More than 50% of DHCWs
      said they did not have sufficient information to safely and effectively provide
      care for HIV-infected patients. Use of infection control techniques varied
      considerably. Parenteral injuries were relatively high, but only 5% of DHCWs
      believed they could have been exposed to HIV from these occurrences, and few
      DHCWs sought medical evaluation. Less than 45% of offices had a blood/body fluid
      exposure staff protocol, and few offices had a policy for HIV-infected staff.
      Nearly twice as many DHCWs said offices have an ethical versus a legal duty to
      treat HIV-infected persons. Low percentages of DHCWs believed the private
      practice dental office is the best place to treat HIV-infected patients, but
      approximately 50% said they would provide care. Twenty percent indicated that a
      diagnosed HIV-infected person had been seen at their office. Seventy-six percent
      said staff had been uncomfortable treating HIV-infected patients, 14% said staff
      had refused to treat, and 10% said referrals were difficult. DHCWs exhibited
      substantial improvements in their HIV-related KAPs compared to previous surveys.
      Nevertheless, additional cognitive and behavioral changes are necessary to ensure
      that all DHCWs provide care with the highest technical, legal, and ethical
      standards for all patients.

PMID- 1388958
TI  - Inhibition of human renin by rat plasma. Rat angiotensinogen is a competitive
      inhibitor of the human renin-substrate interaction.
AB  - Human renin can cleave rat angiotensinogen, yet infusion of human renin into rats
      causes only a modest increase in blood pressure. We therefore investigated
      whether there is a factor in rat plasma which inhibits human renin activity. The
      addition of 20% normal rat plasma to human plasma had a slight, but not
      significant, inhibitory effect on the rate of angiotensin formation, while
      nephrectomized rat plasma, which had a seven-fold higher concentration of
      angiotensinogen, caused a dose dependent inhibition (20 to 70%). The rat plasma
      inhibitor copurified with angiotensinogen. Analysis of the kinetics of the human
      renin-human substrate reaction and of the human renin-rat substrate reaction
      revealed that the rate of angiotensin I production in the presence of both
      substrates could be entirely accounted for by assuming that rat and human
      angiotensinogens are competitive inhibitors of each other. These results show
      that human renin can cleave rat substrate but the reaction rate is extremely slow
      relative to the cleavage of human angiotensinogen. They also indicate that rat
      angiotensinogen is an effective competitive inhibitor of the human renin
      substrate reaction. These results may be relevant to the development of renin
      inhibitors and to transfection studies involving heterologous renin or substrate
      genes.

PMID- 1388959
TI  - Metabolic cardiovascular risk factors and sodium sensitivity in hypertensive
      subjects.
AB  - Hypertension has previously been suggested to be a part of a metabolic syndrome
      also involving hyperlipidemia, hyperinsulinemia, and decreased insulin
      sensitivity. In the present study, 10 untreated hypertensive subjects were
      challenged with a high-salt diet (20 g NaCl) for 1 week after 7 days on a low
      salt diet (less than 3 g). The difference in mean blood pressure (MBP) at the end
      of the high-salt diet v the low-salt diet was denoted salt sensitivity. We
      related the salt sensitivity to indices of glucose and lipid metabolism and
      studied the effect of salt deprivation on these metabolic variables. Salt
      sensitivity was found to be significantly correlated to HDL cholesterol (r =
      0.79, P less than .007), insulin sensitivity (M value at the euglycemic clamp, r
      = 0.68, P less than .003), and fasting serum insulin (r = 0.69, P less than .04).
      Salt deprivation induced an increase in fasting insulin (P less than .03), but
      did not significantly affect any other indices of glucose and lipid metabolism.
      In conclusion, our study shows that hyperinsulinemia, decreased sensitivity to
      insulin, and low levels of HDL cholesterol were most commonly seen in
      hypertensive subjects with a low sodium sensitivity. A putative mechanism might
      be an increased activity in pressor systems also affecting glucose and lipid
      metabolism.

PMID- 1388960
TI  - Improvement in metabolic risk factors for coronary heart disease associated with
      cilazapril treatment.
AB  - Patients with hypertension tend to be glucose intolerant, hyperinsulinemic, and
      dyslipedemic. Since all of these changes increase risk of coronary heart disease
      (CHD), it is important to know what effect antihypertensive treatment has on
      these variables. The current open-labelled, uncontrolled study was initiated in
      order to extend our understanding of these issues. This study was performed in 19
      patients with hypertension who were started on an angiotensin converting enzyme
      (ACE)-inhibitor, cilazapril, with hydrochlorothiazide (HC) added if needed to
      control blood pressure. Plasma glucose and insulin responses to oral glucose and
      lipid concentrations were measured before, 26, and 52 weeks after starting
      treatment. Patients treated with either cilazapril (n = 9) or cilazapril+HC (n =
      10) did not differ in terms of original (mean +/- SEM) blood pressure (159 +/-
      5/101 +/- 1 v 156 +/- 4/103 +/- 2 mm Hg), age (53 +/- 2 v 54 +/- 2 years), sex
      distribution (5M:4F v 7M:3F), or body mass index (24.4 +/- 0.5 v 24.2 +/- 0.9
      kg/m2). Blood pressure was also similar after 26 (137 +/- 4/88 +/- 1 v 133 +/-
      3/90 +/- 1 mm Hg) and 52 (137 +/- 4/87 +/- 1 v 134 +/- 4/89 +/- 2 mm Hg) weeks of
      treatment. Plasma glucose and insulin responses decreased by 8 +/- 3% (P less
      than .05) and 25 +/- 9% (P less than .002), respectively, in cilazapril-treated
      patients, but did not change in those treated with cilazapril plus HC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1388961
TI  - Dietary sodium and the antihypertensive effect of nifedipine in spontaneously
      hypertensive rats.
AB  - To assess the interaction of dietary sodium and the antihypertensive response to
      a calcium antagonist, spontaneously hypertensive rats (SHR) were given a diet of
      regular or increased (120 v 342 mumol Na+/g food) sodium intake from 4 until 16
      weeks of age. Nifedipine was added at 10 weeks of age. This level of sodium
      intake did not enhance the development of hypertension in SHR. In rats with the
      regular sodium intake, nifedipine caused only a minor decrease in blood pressure.
      In contrast, with increased sodium intake nifedipine caused a marked
      antihypertensive response, preventing the rise in blood pressure occurring
      between 10 and 16 weeks of age. This enhanced response was associated with a
      diminished blood pressure fall from ganglionic blockade. These results indicate
      that modest increases in sodium intake enhance the blood pressure response to a
      calcium antagonist possibly by potentiating its inhibitory effects on sympathetic
      activity.

PMID- 1388962
TI  - The influence of age on renal function and renin and aldosterone responses to
      sodium-volume expansion and contraction in normotensive and mildly hypertensive
      humans.
AB  - To determine the effects of age on the responses of renin, aldosterone (PA),
      sodium excretion, and renal function to provocative maneuvers, we performed
      volume expansion and contraction in 390 normotensive and 212 hypertensive
      subjects in the second to seventh decades of life. The subjects were classified
      as Na-sensitive if their mean blood pressure was 10 mm Hg or more higher after
      volume expansion than volume contraction. Sodium sensitivity was associated with
      hypertension and increasing age. Plasma renin activity decreased with age under
      basal, stimulated, and suppressed conditions; the decrease was greater in
      hypertensives than in normotensive persons. The PA values were greater in
      hypertensives than in normal subjects after volume expansion. There was an age
      related decrease in PA values after volume contraction in normal, but not in
      hypertensive, persons. With volume expansion, hypertensive persons exhibited
      "exaggerated natriuresis." There was an age-related increase in natriuresis in
      both groups; the increase was greater in hypertensives than normal subjects.
      Creatinine clearance decreased with age; however, the rate of decrease in this
      cross-sectional study was not different in hypertensive and normotensive
      subjects. These observations may have a bearing on why NaCl affects the blood
      pressures of older individuals more than younger persons.

PMID- 1388964
TI  - Intraluminal pressure modulates vascular contractility of perfused mesenteric
      resistance arteries. Altered response in hypertension.
AB  - Intraluminal pressure may affect vascular contractility in both normotension and
      hypertension. To test this hypothesis, we studied mesenteric resistance arteries
      from normotensive humans as well as normotensive (WKY) and spontaneously
      hypertensive (SHR) rats (internal diameter 214 +/- 27, 201 +/- 6, and 172 +/- 6
      microns, mean +/- SEM at 10 mm Hg). Vessels were mounted on glass cannulas and
      perfused in organ chambers filled with buffer solution at intraluminal pressures
      of 10 to 120 mm Hg; vasomotion was measured using a video dimension analyzer.
      Under baseline conditions (10 mm Hg), wall thickness was 36 +/- 4 microns in
      humans, 32 +/- 4 microns in WKY, and 47 +/- 2 microns in SHR (P less than .001).
      With increasing pressure, the diameter of human vessels increased up to 25 mm Hg
      and remained constant at higher pressures. In contrast, resistance arteries of
      normotensive and hypertensive rats exhibited an almost linear increase in
      diameter over the whole pressure range. In SHR, the pressure-diameter
      relationship was much flatter than that of WKY, indicating reduced compliance. In
      human arteries, the contraction to KCl was maximal at 25 mm Hg and averaged 40 +/
      6%. Both above and below 25 mm Hg, the response declined to a minimum of 17 +/-
      2% at 120 mm Hg (P less than .01). Similar results were obtained in WKY rats. In
      contrast, the contractile response in SHR remained maximal over the entire
      pressure range studied (65 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388963
TI  - The reliability of noninvasive continuous finger blood pressure measurement in
      patients with both hypertension and vascular disease.
AB  - In conditions of compromised peripheral circulation, the measurement of
      noninvasive continuous finger blood pressure with the Finapres device may show
      reduced accuracy. We therefore compared Finapres blood pressure (FINAP) with
      intrabrachial blood pressure (IAP) responses to the Valsalva maneuver and arising
      in 12 patients in whom the peripheral circulation was expected to be compromised
      due to the combination of therapy-resistant hypertension and vascular disease.
      During a 30 sec control period the FINAP--IAP differences were -15.7 +/- 18.8 mm
      Hg (mean +/- SD) for systolic, -20.1 +/- 15.7 mm Hg for mean, and -13.5 +/- 15.7
      mm Hg for diastolic pressure. During the Valsalva maneuver and prolonged standing
      Finapres reproduced the essential characteristics of the changes in IAP in all
      patients. However, in individual patients, the magnitude of the intraarterial
      blood pressure response was sometimes over- or underestimated by Finapres.
      Nevertheless, the group averaged blood pressure, in particular mean and diastolic
      pressure, response to cardiovascular stimuli, was well reproduced by Finapres. In
      conclusion, as expected physiologically, individual Finapres measurements in
      patients with vascular disease do not always equal the intrabrachial pressure and
      should thus be evaluated with care. However, the Finapres device can be used with
      sufficient confidence to study the group averaged responses to cardiovascular
      stimuli in these patients.

PMID- 1388965
TI  - The effect of intermittent exposure to cold on the development of hypertension in
      the rat.
AB  - Continuous exposure to a cold (5 degrees C) environment has been shown to induce
      hypertension in rats. The total time required for the first significant elevation
      of blood pressure is dependent on a number of factors, including the ambient
      temperature and the weight of the rat at the time of exposure to cold. The
      present study was also concerned with the minimal time of daily exposure to cold
      that would result in a significant elevation of blood pressure. To achieve this,
      we used four groups of rats. One was exposed to cold for 4 h daily (09:00 to
      13:00), a second group was exposed to cold for 8 h daily (09:00 to 17:00), and a
      third was exposed for 24 h daily. The fourth group remained at 25 degrees C.
      Systolic blood pressures of the group exposed to continuous cold became elevated
      significantly above pre-cold exposure level within 2 weeks of cold exposure.
      Blood pressures of the groups exposed to cold for 4 and 8 h daily became elevated
      significantly above the level of the warm-adapted control group by day 27 of
      exposure to cold, but failed to reach the level of the chronically cold-exposed
      group even after 42 days of exposure to cold. There was a sigmoid-type
      relationship between the hours per day exposed to cold and systolic blood
      pressure at the end of the experiment. Thus, graded elevations of systolic blood
      pressure occur with increasing daily duration of exposure to cold.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1388967
TI  - Concomitant release of renin, angiotensin I, and angiotensin II during
      superfusion of human juxtaglomerular cell tumor.
AB  - Increasing evidence indicates that angiotensin II can be formed by
      juxtaglomerular cells (JGC) and cosecreted with renin. We investigated the
      existence of this local renin-angiotensin system in a human JGC tumor, using an
      in vitro superfusion. The JGC tumor was found concomitantly to release renin and
      angiotensin I and II. Sequential addition of atrial natriuretic peptide,
      dopamine, and a somatostatin analog in the superfusion did not affect renin or
      angiotensin I and II release. The data provide evidence that the human JGC tumor
      in vitro generates angiotensin II, and supports its possible role as a local in
      vivo regulator of kidney function.

PMID- 1388966
TI  - Dissociation of hypertension and genetically enhanced cell growth capacity in
      skin fibroblasts of F2 hybrid spontaneously hypertensive rats/Wistar-Kyoto rats.
AB  - Skin fibroblasts from newborn spontaneously hypertensive rats (SHR) grow faster
      in culture than Wistar-Kyoto rat (WKY) cells. Similar results have been described
      for vascular smooth muscle cells from prehypertensive and adult SHR. This
      suggests the existence of an intrinsic abnormality in vascular and nonvascular
      cells of mesodermal origin affecting cell growth control in those rats. In an
      attempt to determine the relation between high blood pressure and this trait, we
      cultured skin fibroblasts from adult SHR, WKY, F1, and F2 hybrid SHR/WKY
      populations by explant technique. Their growth capacity was determined by culture
      well DNA doubling time and by [3H]thymidine incorporation. Adult SHR fibroblasts
      grew more quickly (doubling time [DT] = 37.2 +/- 2.3 h, n = 8) than WKY ones (DT
      = 53.9 +/- 3.6 h, n = 6). Female SHR were crossed with male WKY to produce an F1
      and an F2 hybrid generation presenting a Mendelian distribution of blood
      pressure. Skin fibroblasts were cultured from 21 rats belonging to the highest
      and the lowest blood pressure groups. No difference was observed between the two
      groups in either growth (DT = 47.5 +/- 4.1 h, n = 11 v DT = 44.6 +/- 3.2 h, n =
      10) or epidermal growth factor-induced [3H]thymidine incorporation. These
      observations suggest that the increased growth capacity observed in SHR is not a
      determinant of high blood pressure initiation but may be involved in early
      cardiovascular enlargement.

PMID- 1388969
TI  - Exercise for the treatment of hypertension. Help or hype.

PMID- 1388968
TI  - Prevalence of left ventricular hypertrophy and cardiac arrhythmias in borderline
      hypertension.
AB  - Seventy-eight men with borderline hypertension according to the World Health
      Organization criteria underwent echocardiographic examination, followed by
      simultaneous ambulatory blood pressure and electrocardiographic monitorings for
      24 h. The prevalence of echocardiographic left ventricular hypertrophy was 16.6%
      (13/78). Borderline hypertensives with left ventricular hypertrophy had more
      supraventricular (P less than .001) and ventricular ectopic beats (P less than
      .001) than normotensive controls and borderline hypertensives without cardiac
      involvement. Furthermore, ventricular ectopic activity was significantly related
      to left ventricular mass (r = 0.58, P less than .05) in borderline hypertensives
      showing echocardiographic evidence of left ventricular hypertrophy. Our findings
      suggest that noninvasive assessment of target organ status, including
      echocardiography, should be employed to optimize risk stratification in
      borderline hypertension.

PMID- 1388970
TI  - Clinical neurophysiology. A name in search of a practice!

PMID- 1388971
TI  - Current status of chairpersons in physical medicine and rehabilitation.
AB  - There are currently 77 academic departments, divisions or units of physical
      medicine and rehabilitation (PM&R) in the United States. The authors conducted a
      survey to develop a profile of the current chairpersons of PM&R, as well as to
      assess the short- and long-term needs of the field. The survey addressed basic
      demographic information as well as the level of formal training and/or experience
      in various management, patient care and academic areas. The level of satisfaction
      with various aspects of the position such as workload, relationship with the
      university and role as a researcher were also measured. The chairpersons were
      asked when they plan to vacate their position and if they felt there were any
      members of their faculty who are qualified and ready to assume a chairperson
      position. Those that identified a qualified individual were then asked whether
      the person had formal training and/or experience in the various management,
      patient care and academic areas. The results indicate that, although the
      chairpersons have a high level of job satisfaction with respect to the challenge
      of the position and their administrative and supervisory roles, they are least
      satisfied with their role as a researcher. The field must be concerned with this
      finding, because academic PM&R units in the United States will experience a
      substantial change in leadership by the end of the 20th century. Approximately
      39% of the current chairpersons who returned the questionnaire are planning to
      step down by 1999, with an additional 37% unsure when they will vacate the
      position.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388972
TI  - Standardized nerve conduction studies in the upper limb of the healthy elderly.
AB  - Nerve conduction studies are increasingly being performed on elderly individuals;
      however, no standardized data for the elderly population exists to provide an
      accurate interpretation of electrodiagnostic findings. The purpose of this study
      was to provide standardized data in the healthy elderly for the nerves of the
      upper limb that are routinely chosen for study by electromyographers. Nerve
      conduction studies were performed prospectively in one upper limb of 155
      carefully screened healthy elderly individuals between the ages of 60 and 95
      years. Upper limb temperature was controlled to limit the influence of
      temperature on the measured conduction parameters. Standard nerve conduction
      techniques using constant measured distances were applied to evaluate the median,
      ulnar and radial nerves. A normative electrodiagnostic database for elderly
      individuals was established in this study. The mean nerve conduction parameters
      of this healthy elderly population compared favorably with existing literature
      values for younger populations. However, age had a statistically significant but
      low strength effect on all ulnar nerve conduction velocities and distal latencies
      as well as the distal sensory amplitudes of all three nerves. Gender had a
      greater effect than age on these parameters as well as on median sensory distal
      latency. Other median motor and sensory conduction parameters along with radial
      sensory distal latency were not significantly related to age or gender based on
      two-way analysis of variance.

PMID- 1388973
TI  - Analysis of mechanical and metabolic factors in the gait of congenital below knee
      amputees. A comparison of the SACH and Seattle feet.
AB  - Prosthetic feet have been developed with the intention that they deform during
      the first half of the stance phase to store energy that can be released at the
      end of stance and contribute to push-off. The purpose of this study was to
      examine the three-dimensional kinematics and kinetics of gait and metabolic
      energy cost in children and adolescents with below-knee amputations using the
      SACH and Seattle prosthetic feet. The metabolic test consisted of an 8-min walk
      around an oval track while expired gases were collected and analyzed. The
      biomechanical test consisted of 10 walking trials: 5 for each of the prosthetic
      and sound limbs. Stance and swing phase moments and powers were calculated for
      both the prosthetic and sound limbs. A four-camera VICON system recorded
      movements of the limb segments to calculate joint kinematics, and these were
      combined with ground reaction force data in a three-dimensional model to
      determine moments and powers about the hip, knee and ankle joints. The Seattle
      foot produced a small increase in stride length, which led to a small increase in
      walking velocity. Biomechanical data revealed that the Seattle foot was less
      resistant to passive dorsiflexion in midstance, and although there was no effect
      on the work done across the prosthetic ankle, a knee flexor moment dominated the
      stance phase when the SACH foot was tested, whereas the Seattle foot allowed a
      normal extensor moment. The profile of work was unaffected by the type of foot.
      On the sound side, the hip produced most of the positive work while the ankle
      output was below normal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1388974
TI  - Lack of effect of amitriptyline in murine myotonia.
AB  - Amitriptyline, a tricyclic antidepressant, has been reported to diminish signs of
      human myotonic muscular dystrophy, but has not been examined in other myotonias.
      Normal and myotonic (ADRmto) mice were injected acutely with either
      amitriptyline, phenytoin, procainamide or 0.9% saline. In addition, two groups of
      myotonic mice were injected chronically with either 0.9% saline or amitriptyline
      for 28 days. Behavior, assessed before injection using a "drop test," was re
      evaluated at 30-min intervals for up to 180 min postinjection, as well as at the
      end of the 28-day chronic trial. If improvement in behavior was noted, the mice
      were then evaluated with insertional needle electromyography (EMG) and in vitro
      contractility (maximal tetanic tension and relaxation time) studies. Neither
      acute nor chronic amitriptyline administration had any beneficial effect on
      behavior, EMG or contractile parameters in myotonic mice. Phenytoin abolished
      abnormal EMG activity and improved behavior. Procainamide improved behavior and
      contractility parameters but had no effect on EMG. These results confirm that the
      myotonic mouse is responsive to classic antimyotonic agents, but not to
      amitriptyline.

PMID- 1388975
TI  - Linearity and reliability of the IEMG v torque relationship for the forearm
      flexors and leg extensors.
AB  - The purpose of this investigation was to examine the linearity and reliability of
      the surface integrated electromyogram (IEMG) v isometric torque relationship for
      the leg extensors and forearm flexors. Nine men and four women (mean age +/- SD =
      22 +/- 2 yr) volunteered for this investigation. Isometric testing was conducted
      on a Cybex II isokinetic dynamometer with the lever arm at 0.785 rad (45 degrees)
      below the horizontal plane for the leg extensors and in the vertical plane for
      the forearm flexors. Bipolar surface electrodes were used to record IEMG values
      from the vastus lateralis and biceps brachii. To examine test-retest reliability,
      two test sessions, separated by a minimum of 48 h, were performed. The test
      retest linearity of the IEMG v torque relationship ranged from r2 = 0.77 to 0.96
      and 0.55 to 0.94 for the forearm flexors and r2 = 0.81 to 0.98 and 0.83 to 0.98
      for the leg extensors. The slope values were not significantly different (P >
      0.05) between sessions and were correlated (intraclass correlation coefficients)
      at R = 0.86 (standard error of estimate (SEE) = 5.77 microV.Nm-1, 31% of the
      mean) and R = 0.97 (SEE = 0.27 microV.Nm-1, 12% of the mean) for the forearm
      flexors and leg extensors, respectively. The test-retest maximal torque values
      were 57.73 +/- 22.57 Nm and 58.14 +/- 22.81 Nm (R = 0.99; SEE = 2.39 Nm) for the
      forearm flexors and 187.79 +/- 55.98 Nm and 195.42 +/- 56.27 Nm (R = 0.96; SEE =
      22.62 Nm) for the leg extensors (nonsignificant differences; P > 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1388976
TI  - Patient awareness of physical medicine and rehabilitation.
AB  - The present study examined the extent to which patients referred to a specialist
      in physical medicine and rehabilitation (PM&R) could correctly identify the name
      or essential scope of the specialty the physiatrist practiced. The hypothesis,
      based on the author's experiences as a staff physiatrist, was that most patients
      would not be aware of the name and scope of the specialty of physical medicine
      and rehabilitation. This prospective study involved the administering of a
      questionnaire to 202 consecutive referrals to a University-affiliated PM&R
      outpatient clinic. Of the respondents, 19% were able to correctly identify that
      the physician they were referred to was either a PM&R specialist, a physical
      medicine specialist, a rehabilitation specialist or a physiatrist. Among the
      incorrect responses, orthopedist, neurologist and rheumatologist were most
      prevalent, and 33% of the respondents thought the physiatrist performed surgery.
      The implications of the findings are discussed. There continues to be a need to
      educate the public about the scope of practice of physiatry.

PMID- 1388977
TI  - Hemiparesis in HIV infection. Rehabilitation approach.
AB  - Persons with acquired immunodeficiency syndrome (AIDS) and human immunodeficiency
      virus (HIV) infection demonstrate a wide array of central nervous system
      impairments and may be at a significantly increased risk for cerebrovascular
      disease. Cerebrovascular disease can be the first manifestation of HIV infection
      and may be associated with a treatable etiology. Anticipating more referrals for
      HIV-related physical disability, we detail the rehabilitation management of three
      persons with HIV infection and hemiparesis. Onset of hemiparesis ranged from just
      before to 24 months after an AIDS-defining illness. No specific underlying
      etiology was identified in two of three patients, consistent with previous
      observations. Rehabilitation interventions included lower and upper extremity
      orthoses, assistive devices to aid gait and activities of daily living,
      therapeutic exercise and use of antispasticity medication. All patients made at
      least mild, temporary gains in functional status. Survival ranged from 3 to >6
      months from initial contact with rehabilitation services. Neurologic and
      nonneurologic considerations in the rehabilitation of persons with HIV infection
      are discussed. We conclude that selected individuals with HIV infection and
      hemiparesis can benefit from rehabilitation intervention. HIV infection should be
      considered in any young adult presenting with stroke.

PMID- 1388978
TI  - Mirror movements in the alien hand syndrome. Case report.
AB  - The alien hand syndrome has been associated with different descriptions of
      abnormal motor behavior. We report on two patients with transient left
      hemiparesis who remained with limb apraxia and were particularly impaired by a
      variety of involuntary skilled movements of their apractic limb. After the report
      and a review of the literature, we discuss the presence of one type of abnormal
      movement observed in this syndrome. These movements resemble the mirror movements
      seen in the normal development of motor control and in some pathologic conditions
      later. Their appearance in the alien hand syndrome seems to demand both
      intrahemispheric and interhemispheric motor pathway damage.

PMID- 1388979
TI  - Clonidine in the treatment of brainstem spasticity. Case report.
AB  - This report describes a patient who developed spasticity after a medullary
      infarct. No improvement in her spasticity was achieved by baclofen therapy and
      the side effects of the drug necessitated its gradual withdrawal. Recent reports
      of the success of clonidine in the management of spasticity due to spinal cord
      injury prompted an attempt at clonidine therapy. When clonidine therapy was
      initiated, the patient responded rapidly with both subjective and objective
      improvements in her spasticity. This case suggests a potential role for clonidine
      in the treatment of spasticity resulting from brainstem infarction.

PMID- 1388980
TI  - Walker modification for ventilator-assisted individuals. Case report.
AB  - A case is presented of a 53-yr-old ambulatory ventilator-dependent individual who
      demonstrated that functional ambulation could be possible with a modified rolling
      walker. The patient used intermittent positive pressure ventilation delivered by
      noninvasive methods 24 h a day. For potentially ambulatory ventilator users,
      intensive rehabilitation and the use of a modified walker can improve medical,
      psychological and social status and permit the resumption of vocational
      activities. Mouth intermittent positive pressure ventilation is the method of
      choice for daytime ventilatory support during ambulation for individuals with
      severe chronic alveolar hypoventilation because of predominantly restrictive
      pulmonary syndromes.

PMID- 1388981
TI  - Making rehabilitation specialty certification more objective and realistic. A
      commentary.

PMID- 1388982
TI  - Rebalancing the aging adjustment. A commentary.

PMID- 1388983
TI  - AIDS epidemiology and pathology. Implications for intensive care units.
AB  - The acquired immunodeficiency syndrome (AIDS) evolves from infection with the
      human immunodeficiency virus (HIV). The HIV attacks the hosts' immune and
      neuroendocrine systems, rendering the host susceptible to a myriad of chronic and
      acute conditions requiring intensive care. This article reviews epidemiologic and
      pathologic trends associated with HIV infections that have the potential to
      increase demands for admission to intensive care units. Research describing
      potential predictors of survival among patients with HIV-related conditions is
      also described. In addition, possible implications for practice, education, and
      research are discussed.

PMID- 1388984
TI  - Opportunistic infections and pharmacology.
AB  - The most common acute complication in HIV infection is likely to be one of the
      many possible opportunistic infections caused by immunodeficiency. These
      infections may be the index diagnosis of AIDS or occur in previously diagnosed
      patients as additional problems. Monitoring for the symptoms of disease and
      monitoring patients while undergoing treatment are frequently included in nursing
      care. This article discussed the diagnosis and treatment of some of the more
      common of the major opportunistic infections seen in AIDS.

PMID- 1388985
TI  - Infection prevention and control.
AB  - Nurses are clearly at risk for exposure to HIV through blood and body fluids, and
      they frequently use needles and sharp objects. In addition, critical care
      patients are at high risk for nosocomial infections due to other etiologic
      agents. This article addresses reducing the risk of infection for both nurses and
      patients using a variety of strategies.

PMID- 1388986
TI  - Psychosocial and neuropsychiatric care.
AB  - Psychosocial problems of persons with HIV disease require knowledge and skill in
      psychosocial assessment, suicide risk assessment, crisis intervention and various
      other therapeutic modalities, provision of social and community resources, and
      spiritual care. Neuropsychiatric problems require knowledge and skill in
      neurologic, cognitive, and behavioral assessment and supportive care. Families
      and partners have needs commensurate with those of the person with HIV disease.

PMID- 1388987
TI  - The HIV epidemic. Ethical issues for the next decade.
AB  - The HIV epidemic and ethical issues will continue to be a major topic of
      discussion over the next decade. It is now evolving into a new phase and we are
      experiencing a change or shift in the populations that are affected. This article
      focuses on the issues of early intervention, access to care, and the continuum of
      care including a discussion of case management, the changing populations, drug
      trials, and issues surrounding confidentiality.

PMID- 1388988
TI  - Nursing effectiveness research and patient outcomes. A challenge for the second
      HIV/AIDS decade.
AB  - The need to focus on the nursing care of the acute and chronically ill HIV
      infected person is made apparent by an examination of recent data on the
      prevalence of this disease. A nursing system framework of quality of care is
      proposed, which includes patient problems (inputs), nursing care activities
      (processes), and patient outcomes (outcomes). Examples from ongoing research are
      provided.

PMID- 1388989
TI  - Women in the HIV epidemic.
AB  - In the United States, the majority of women with HIV/AIDS are women whose lives
      have been touched by injection drug use--their own or that of their sexual
      partners. The pattern of opportunistic infections in women is more similar to
      that of injection drug users than that of homosexual men. Specific complications
      associated with a woman's reproductive tract include persistent Candida
      vaginitis, human papillomavirus infections, cervical dysplasias, and, possibly,
      pelvic inflammatory disease. Childbearing decisions for women with HIV infection
      are complex and culturally mediated. Meeting the challenge of providing high
      quality services to women with HIV infection requires major changes in the
      service delivery system.

PMID- 1388990
TI  - Pediatric HIV/AIDS.
AB  - The number of children infected with HIV is growing, and new treatments are
      extending their survival. Nurses, including pediatric intensive care nurses, more
      frequently have to care for HIV-infected children. This article discusses the
      transmission of HIV in children, pediatric manifestations of the disease,
      staging, treatment, and prophylaxis. The complications, treatment, and
      psychosocial and ethical issues of the child with HIV in the pediatric intensive
      care unit are examined.

PMID- 1388991
TI  - Caring for the adolescent with HIV infection or AIDS in the critical care
      setting.
AB  - Caring for the adolescent with HIV infection or AIDS in the critical care setting
      is challenging. This article discusses medical treatments for HIV, aspects of
      adolescent development that influence their behaviors, certain behaviors that put
      adolescents at risk for HIV acquisition, ethical and legal concerns for caring
      for this population, nursing implications for care, and the needs of nurses
      caring for this population.

PMID- 1388992
TI  - Neonatal nursing assessment by functional health patterns.
AB  - This article provides nurses who care for infants with a tool to document both
      physical examination and nursing assessment. Specific information to gather data
      and where to organize initial data are described. This tool also accommodates
      documentation of the first minutes of assessment and treatment provided when
      delivering care to critically ill infants on admission to the unit. In addition,
      it provides a means of further documenting nursing assessment information at a
      later time (e.g., psychosocial needs). The functional health patterns are a
      framework to organize the nursing assessment of the neonate and his or her
      family, and this assessment is the data base for both nursing diagnosis and
      individualized care planning.

PMID- 1388994
TI  - Group B streptococcal infection in the newborn.
AB  - This article reviews the immunologic and microbiologic characteristics of the
      group B streptococcal organism, perinatal acquisition, clinical presentation, and
      therapy. A discussion of immunoglobulin transfusion therapy is included, and a
      case study is presented.

PMID- 1388993
TI  - The drug-exposed infant.
AB  - Drug use is a widespread problem within our society. This problem is becoming
      more prevalent within the perinatal population, thus affecting the neonatal
      population. This article explores the effects of alcohol, cocaine, and opiates on
      the pregnancy and neonatal outcome.

PMID- 1388995
TI  - Neonatal seizures.
AB  - Seizures are a frequent symptom seen in intensive care nurseries and may be the
      only sign of a central nervous system disorder in the neonate. The clinical
      manifestations of neonatal seizures are widely variable and may be indicative of
      alternate pathophysiology. The advent of portable video electroencephalographic
      monitoring has improved the ability to correlate clinical behaviors with
      electrocortical activity and may facilitate diagnosis. The ability to accurately
      recognize seizures and determine their cause is crucial to providing treatment.

PMID- 1388996
TI  - New trends in neonatal mechanical ventilation.
AB  - Advances in technology have produced more sophisticated, diverse modes of
      mechanical ventilation. Efforts to reduce neonatal morbidity and mortality have
      led clinicians to use a myriad of ventilatory support modalities. It is
      imperative that critical care nurses become aware of the indications, advantages,
      and disadvantages of the new modes of ventilatory support. This article reviews
      respiratory physiology and presents new trends in neonatal mechanical
      ventilation.

PMID- 1388997
TI  - Surfactant replacement therapy in newborns with hyaline membrane disease.
AB  - This article discusses the use of surfactant replacement therapy in the
      management of neonates with hyaline membrane disease (HMD). Included is an
      overview of HMD, current treatment modalities, a case presentation, nursing
      implications for managing the infant with HMD, and a nursing care plan.
      Administration of surfactant is discussed, along with implications for nursing
      research.

PMID- 1388998
TI  - Cardiac transplantation in early infancy.
AB  - Congenital heart disease (CHD) encompasses a full spectrum of severity, ranging
      from physiologically insignificant (those lesions ameliorated over time without
      surgical or medical intervention) to those lesions that result in certain death
      in early infancy. Recent attempts at heart and heart-lung transplantation and
      surgical palliation have provided options for families of infants at the deadly
      end of this spectrum. The purpose of this article is to outline the process of
      one form of intervention--heart replacement during early infancy. The main
      concerns following transplantation are rejection and infection, but survival
      rates after transplantation show a good 5-year prognosis in this young age group.

PMID- 1388999
TI  - Neonatal pain management.
AB  - Neonatal pain management is a challenge for the clinician. Research is just
      beginning to uncover the neonates' capability of expression of pain, explore
      pharmacologic management strategies, and identify the spectrum of intrusions that
      may precipitate pain or distress in the critically ill neonate. This article
      reviews the neonatal biologic, behavioral, and physiologic responses to pain and
      describes recommendations for clinical management and decision-making.

PMID- 1389000
TI  - Intracerebral arteriovenous malformations presenting as neonatal congestive heart
      failure.
AB  - Intracerebral arteriovenous malformations (AVM) are a complex medical emergency
      in neonates. AVMs are congenital communications between the arterial and venous
      circulation. Occurring early in gestation, they may enlarge over time,
      promulgating a left-to-right shunt. This volume overload can present as severe
      congestive heart failure or as pronounced shock. This article discusses the
      pathophysiology, clinical presentation, diagnostic modalities, treatment
      regimens, nursing implications, and complications of cerebral AVMs. A case study
      is also presented.

PMID- 1389001
TI  - Citalopram and 8-OH-DPAT attenuate nicotine-induced excitation of central
      noradrenaline neurons.
AB  - Previous electrophysiological studies have demonstrated that nicotine,
      intravenously administered, excites noradrenergic neurons in the locus coeruleus
      (LC) indirectly by releasing excitatory amino acids (EAA). In the present study
      the excitatory action of nicotine was inhibited by treatment with the selective 5
      HT re-uptake inhibitor citalopram or the 5-HT1A receptor agonist 8-OH-DPAT. It is
      proposed that the antagonism between nicotine and citalopram or 8-OH-DPAT
      reflects an interaction between endogenous EAA, e.g. glutamate, and 5-HT. The
      results may, on a cellular basis, explain the attributed effectiveness of drugs
      that facilitate serotonergic neurotransmission in promoting smoking cessation.

PMID- 1389003
TI  - Changes in body temperature markedly affect striatal dopamine release and
      metabolism: an in vivo study.
AB  - Dopamine release and metabolism in the corpus striatum increased markedly when
      the core body temperature of anesthetized rats was increased from 35 degrees to
      41 degrees C while temperatures below 34 degrees were associated with a marked
      attenuation of dopamine release. These observations may have clinical relevance
      in cases where alterations in body temperature are associated with extrapyramidal
      dysfunction.

PMID- 1389002
TI  - The effect of chronic unpredictable stress on locomotor and exploratory activity
      in male rats with different endogenous prolactin levels.
AB  - The probable role of prolactin (PRL) on the behavioral responses evoked by
      chronic unpredictable stress (CUS) was studied in adult male rats. Three
      experiments were performed examining the effect of CUS on behavioral performance
      in: (i) intact rats with normal endogenous PRL levels, (ii) rats with high
      endogenous PRL levels, and (iii) rats with low endogenous PRL levels. Behavioral
      parameters studied were: locomotion, head-dipping, rearing and grooming.
      Endocrine parameters studied were: PRL and corticosterone (C) plasma
      concentrations. In Experiment (i) results showed that CUS inhibited significantly
      locomotion, head-dipping and rearing activity. No variations in PRL plasma levels
      were found but a significant increase in C was detected. In Experiment (ii) the
      hyperprolactinaemia induced by pituitary transplants in the kidney capsule
      blocked partially the inhibition of locomotion due to CUS. No modifications on
      head-dipping, rearing and grooming were observed. PRL levels in these rats were
      consistently high as expected and CUS regimen did not change the hormone
      concentrations in blood. The C response due to CUS, however was completely
      blocked in the pituitary-implanted group. In Experiment (iii), repeated treatment
      with bromocriptine (5 mg/kg i.p.) significantly increased the inhibitory effect
      of CUS on locomotion, head-dipping and rearing. Grooming was also decreased in
      CUS-treated rats. PRL levels in these animals was low as expected and the C
      response due to CUS was significantly increased. Results give support to the
      concept that PRL may have a regulatory role in CUS.

PMID- 1389004
TI  - L-dopa infusion mode differentially affects corpus striatal dopamine efflux in
      the presence of reserpine.
AB  - In the present experiment we tested the effects of L-DOPA upon dopamine (DA)
      efflux in vitro from superfused corpus striatal tissue fragments in medium
      containing reserpine. The purposes of this experiment were first, to evaluate the
      effects of differing infusion modes of L-DOPA upon DA efflux under conditions in
      which DA storage capacity has been diminished, and second, to compare this L-DOPA
      stimulated DA efflux with that of other putative DA secretagogues such as
      amphetamine and potassium. No differences were obtained in stimulated DA efflux
      between superfusions performed in the presence or absence of reserpine (10
      microM) in the medium when L-DOPA (5 microM) was infused in a continuous (70
      minute) mode during the superfusion. In contrast, a continuous infusion of either
      amphetamine (10 microM) or high potassium (30 mM) resulted in significantly
      greater stimulated DA efflux in superfusions performed with reserpine in the
      medium. In addition, when L-DOPA (5 microM) was administered for a brief 10
      minute infusion period, a significantly greater stimulated DA efflux was obtained
      with superfusions containing reserpine in the medium. These results suggest that
      the mode of L-DOPA infusion may be an important factor in regulating DA release
      under conditions of diminished DA storage capacity.

PMID- 1389005
TI  - Blood-CSF barrier permeability and central nervous system immunoglobulin G in
      schizophrenia.
AB  - The ratio of albumin in cerebrospinal fluid (CSF) to serum may serve as an index
      of the integrity of the blood-CSF barrier, with increases in this ratio
      indicating increased permeability. The ratio of immunoglobulin G (IgG) in CSF to
      serum (divided by the albumin ratio to correct for variance in blood-CSF
      permeability) represents an index of the endogenous production of IgG in the
      central nervous system (CNS), with increases reflecting a possible infectious
      and/or autoimmune process stimulating central IgG synthesis. We analyzed
      simultaneously collected CSF and serum samples from 46 schizophrenic subjects, 8
      of whom were studied both on and off neuroleptic treatment, and samples from 20
      normal controls. The data indicated increases in CSF/serum albumin ratios or
      CSF/serum IgG indices in 22% and 20%, respectively, of the schizophrenic
      patients. Only 3 patients showed elevations in both indices. Comparison of values
      on and off neuroleptics indicated no significant effect of neuroleptics on these
      indices.

PMID- 1389006
TI  - Journal of Blood Purification: who needs it?

PMID- 1389007
TI  - Dose of dialysis: what index?
AB  - Wider patient acceptance criteria in hemodialysis (HD) programs do not seem to
      completely explain the increasing mortality reported in the United States at a
      time characterized by reduced treatment time and dose. This raises the question
      of HD standard and adequacy. It stimulated us to analyze patient survival with
      unchanged 'old-times' methods. 445 unselected patients have been treated for 22
      years by the same unchanged methods (24 m2/week, flat-plate dialyzers, cuprophane
      membrane, acetate buffer). Their survival data were compared to major HD
      registries and series. Survival was also evaluated as a function of mean arterial
      pressure (MAP), urea fractional clearance (Kt/V), and middle-molecule dialysis
      index (DI). Kaplan-Meier (with log-rank test) analysis and Cox proportional
      hazard model were used. Survival at short and long term was better in our series.
      This favorable survival difference was more obvious for older patients at the
      start of HD. It could not be accounted for by selection bias, but correlated with
      good MAP control without medication and with higher than usual Kt/V (1.67 +/-
      0.41) and DI (1.47 +/- 0.38). Cox analysis including five covariates confirmed
      that survival was linked to MAP. It suggested that survival improvement might be
      expected from a DI increment of over 1.38 but not from a Kt/V increment of over
      1.60. Adequate dialysis cannot be reduced to numbers; it should include both
      sufficient small- and middle-molecule diffusion and ultrafiltration with arterial
      pressure control without need for antihypertensive medication. The long-term
      satisfactory survival remains the best index of overall dialysis adequacy.

PMID- 1389008
TI  - Hemodialysis 1991.
AB  - Hemodialysis remains the principal form of renal replacement therapy worldwide,
      and increasing numbers of patients have survived for 20 years or more. Future
      issues include the incorporation of newer technology into dialysis programs,
      ensuring adequacy of dialysis and optimum quality of care, controlling
      hypertension, and ensuring adequate nutrition. To maximize survival, hypertension
      must be controlled from its onset, smoking must be stopped, adequate dialysis
      provided, normal nutrition maintained, and blood access preserved. Home
      hemodialysis provides the best quality of life and opportunity for
      rehabilitation, but opportunities for this treatment may be limited. The long
      term care of patients with end-stage renal disease requires careful attention to
      all aspects of their treatment on an ongoing basis, potentially for many years.

PMID- 1389009
TI  - Shaded areas of CAPD.
AB  - It is well recognized that CAPD provides many advantageous points compared with
      hemodialysis as a kidney replacement therapy. However, there are a number of
      adverse facts which will result in withdrawal from CAPD. In this article, from my
      own experience on CAPD during the past 12 years, I deal only with shaded areas of
      this dialytic modality, such as the limitation of good candidates for CAPD,
      dysfunction of the peritoneal membrane, infectious complications, metabolic
      abnormalities and psychological stress. My conclusion is that CAPD is one of
      transient replacement therapies, although 'transient' may mean 5 or 6 years.

PMID- 1389010
TI  - Anorexia and malnutrition in hemodialysis patients.
AB  - Malnutrition, which is common in maintenance hemodialysis (HD) patients, is
      strongly associated with increased morbidity and mortality. Protein requirements
      in HD patients are increased twice or more compared to those of healthy subjects.
      Underdialysis leads to anorexia with low protein and energy intake in relation to
      the requirements, resulting in protein and energy malnutrition, generally
      accepted recommendations for dialysis prescription regarding dose of dialysis and
      protein intake are probably inadequately low in relation to the requirements.

PMID- 1389011
TI  - Induction of cytokines by dialysis membranes in normal whole blood: a new in
      vitro assay for evaluating membrane biocompatibility.
AB  - We investigated the capacity of cellulose cuprophane (CUP) and synthetic
      polyacrylonitrile dialysis membranes to induce the production of interleukin 1
      (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha using an in vitro
      model in which normal whole blood is incubated directly with calibrated membrane
      fragments. We found that only CUP membranes significantly increased plasma levels
      of IL-1, IL-6, and tumor necrosis factor alpha. The participation of
      lipopolysaccharide was excluded, since its addition to whole blood incubated with
      CUP led to a synergistic enhancement of IL-1 production, while the addition of
      polymyxin B had no significant effect. Transfer experiments showed that CUP
      pretreated plasma was able to induce cytokine production by autologous monocytes.
      Inactivation of complement components prior to pretreatment abolished this
      effect. The participation of complement activation was further revealed by a
      correlation between cytokine and C5a plasma levels. Lastly, incubation of
      isolated monocytes with CUP but not with polyacrylonitrile also induced cytokine
      production, although to a lesser degree. In conclusion, our simple in vitro model
      can be used to evaluate the biocompatibility of dialysis membranes directly by
      using whole blood with greater relevance to the in vivo situation than models
      based on isolated blood components.

PMID- 1389012
TI  - Reappraisal of long-term renal replacement therapy. Renal transplantation:
      medical versus statistical approach.
AB  - The validity of the numerous statistical methods used for the assessment of the
      results achieved with renal transplantation performed for terminally uremic
      patients may be challenged by a medicalized approach of the patient's post
      transplantation course and outcome. This assumption has been applied to a
      population of 700 patients who received a grafted kidney in our unit between
      November 1972 and December 1990. Among 77 patients who had been followed up for
      10-15 years after grafting, 75% had not suffered any serious related complication
      during the first decade after transplantation. In contrast, among the whole
      transplant population, transplantation entailed either a rapidly fatal issue due
      to an unpredictable and irreversible complication in 45 patients (6.4%), or a
      state of chronic illness with severely disabling complications in 150 others
      (21.5%). At present, the main cause of concern remains, however, the persistent
      long-term graft loss due to chronic rejection. Nevertheless, the advances and
      results achieved in the field of organ transplantation in recent years justifies
      the policy which privileges renal transplantation as the first-choice method of
      renal replacement therapy for every terminally uremic patient aged less than 60
      65 years in whom careful workup does not reveal any clinical/psychological
      contraindication.

PMID- 1389014
TI  - 10th annual meeting of the International Society of Blood Purification. October 7
      9, 1992, Louisville, Kentucky. Abstracts.

PMID- 1389013
TI  - Macromolecule adsorption to hemodialysis membranes depends on molecular size.
AB  - Adsorption to hemodialysis membranes was studied by determining the binding
      kinetics of model macromolecules, polydisperse DEAE dextran (molecular radii 10
      70 A), to an acrylonitrile-methallyl sulfonate copolymer membrane. Hemodialyzers
      were studied in a postdilution hemofiltration circuit where both blood path
      output and ultrafiltrate streams were returned to the reservoir. Changes in the
      reservoir concentration of and sieving coefficients for DEAE dextran were
      monitored over 24 h. Decreases (or increases) in reservoir concentration were
      assumed to result from adsorption to (or desorption from) the membrane. Small
      macromolecules adsorbed rapidly to the membrane but later desorbed. This rapid
      adsorption resulted in low initial sieving coefficients. Large macromolecules
      adsorbed slowly over the entire 24-hour study period. Additional experiments
      suggested that desorption of small macromolecules was due to displacement by
      large macromolecules. Adsorption and desorption of macromolecules to hemodialysis
      membranes are dynamic processes and depend on molecular size.

PMID- 1389015
TI  - [Random breath alcohol screening? Comments on the decisions of the 30th German
      Traffic Legislation Workshop (29 to 31 January 1992 in Goslar)].
AB  - When breathalyser tests are used to detect whether a person in charge of a
      vehicle is incapable of activing due to the influence of alcohol. The
      difficulties which arise are not limited to the extent to which these modern
      methods are forensically sound but extend to the question whether it is legally
      permissible to implement random breathanalysing. It is doubtful whether a duty to
      take a breath test, as yet unrecognized by the law (cf. section 36 Abs. 5 StVO),
      would be in conformity with the constitution. According to the established case
      law of the Constitutional Court nobody can be compelled to put himself in danger
      of incriminating himself under the criminal law by their own act (under the
      principle "nemo tenetur se ipsum accusare"), which in this case would be a hard
      and prolonged breath into a breathalyser. The author sets the strict legal limits
      within which random breathalysing may be enforced.

PMID- 1389016
TI  - [Retrospective analysis of blood collection protocols and blood alcohol analysis
      (Hamburg 1988)].
AB  - 9,361 blood sample protocols (7,264 traffic and 2,097 criminal offences) of 1988
      have been recorded and evaluated by electronic data processing under various
      aspects at the Institute for Legal Medicine in Hamburg. Since 1987 a slight
      increase of total offences was observed with a slight increase of alcohol-related
      traffic delinquency. Other results of the study are: The quota of women and as
      well of young people does not show an increasing tendency in alcoholic offences.
      In most cases older offenders had higher blood alcohol concentrations. More than
      50% of the traffic offenders had a blood alcohol concentration above 1.3%.
      Altogether, criminal offenders had higher blood alcohol concentrations than
      traffic offenders. According to the common drinking- and leisure behaviour most
      of the alcohol delicts happened at weekends around midnight. In more than 50% the
      main traffic delict was drunken driving discovered by police control. Main
      criminal offences were delicts of property, bodily harm and resistance to police
      actions. With regard to alcohol habitation a great number of criminal offenders
      declares constant alcohol consumption, especially a lot of young people (under
      the age of 20). The medical diagnosis mostly pointed to slight or medium degree
      of drunkenness.

PMID- 1389017
TI  - [Comparison of breath and blood alcohol concentration from measurements in police
      work].
AB  - 4.135 measurements of breath- and blood-alcohol concentration were performed by
      police in 1986 and 1987 using the Alcomat A 11 (wavelength 3.4 microns).
      Important conclusions from these measurements can be derived with regard to legal
      breath-alcohol limits. The parameter for judgement is the breath- to blood
      alcohol concentration ratio. Extreme deviations which have to be considered as
      malfunctions were found only in 0.4% of all cases, despite of the fact that not
      all precautions for evidential measurements are fulfilled. The reasons for
      malfunction may result from faulty breath- or blood-alcohol determinations or may
      simply be errors of transfer. The frequency of relatively too high breath-alcohol
      values (e.g. by interfering substances) is nearly the same as of relatively too
      low values (e.g. by too small breath volume). It has to be considered that the
      requirements according to the expertise of the Federal Health Office for
      evidential breath-alcohol measurements are only fulfilled partly. Especially the
      influence of breath-temperature is disregarded although the influence on
      frequency distributions is important as the comparison with other measurements
      demonstrates. A further result shows that the frequency distribution of the
      breath- to blood-alcohol ratio does not depend on blood-alcohol values.

PMID- 1389018
TI  - [Isopropanol and acetone level in serum after preoperative surface disinfection
      with antiseptics containing isopropanol].
AB  - After preoperative skin disinfection in pediatric surgery, serum levels of
      isopropanol up to 12.2 mg/l (MW 5.0 mg/l +/- 3.37, n = 26) were found. They
      result from a rapid and prolonged but uncharacteristic percutaneous resorption of
      the isopropanol-containing disinfectant. In about 50% of the cases, serum levels
      of acetone showed an increase up to 82 mg/l already before skin disinfection,
      presumably caused by preoperative starvation. After skin disinfection, raised
      acetone levels were found in 19 of 26 cases. As increased isopropanol and acetone
      levels are discussed as alcoholism markers, a falsification of congener analysis
      after skin disinfection, e.g. in cases of adult victims of accidents, has to be
      taken into consideration. Endogenous serum levels of methanol (0.87 mg/l +/-
      0.49), ethanol (0.32 mg/l +/- 0.09), acetaldehyde (0.31 mg/l +/- 0.10) and others
      remained unaffected. Some uncharacteristic elevations of propanol-1 levels are
      caused by contaminated rubber caps.

PMID- 1389019
TI  - [Experiences with congener analysis of beverages without congeners].
AB  - Many alcoholic beverages contain no forensically relevant concentrations of
      congeners. Despite this fact they can be subject of a congener analysis. Another
      applicability of congener analyses are cases in connection with a differentiation
      between the short- or longterm ingestion of beverages containing 1-propanol and
      iso-butanol as congeners (e.g. beer or wine).

PMID- 1389020
TI  - Comparison of ethanol concentration in saliva and blood from police controlled
      persons.
AB  - The salivary ethanol concentration correlates very well with the serum level (r =
      0.98) in samples which are obtained almost simultaneously from persons undergoing
      a traffic control. If ethanol was referred to the aqueous compartment the
      saliva/plasma ratio was about 0.85; this ratio was about 11% less than the
      theoretical one and remained constant over the entire concentration range
      applied. Saliva could be taken together with breath samples from traffic
      participants which are controlled for ethanol consumption. The advantage of
      saliva in favour of blood is that it can be obtained nearly simultaneously with
      the breath sample without the intervention of a physician and does not hurt the
      person under suspicion. Furthermore saliva is suited for the voluntary
      surveillance of former alcoholics who are willing to prove that they are able to
      live abstinently.

PMID- 1389021
TI  - [Comment on the contribution by Schoknecht and Hahlbrauck. "Detection of foreign
      gases in breath alcohol analysis"].

PMID- 1389022
TI  - The vulnerability of the hippocampus to protective and destructive effects of
      glucocorticoids in relation to stress.
AB  - The pituitary-adrenal axis participates in the diurnal response of the organism
      to the environment and in its response to stress. Circulating glucocorticoid and
      mineralocorticoid hormones act on cells in the brain via Type I and Type II
      receptors, which operate at the level of gene regulation, and mediate various
      feedback effects of adrenal steroids on brain chemistry and structure, including
      the operation of second-messenger generating systems, levels of structural
      proteins of glial cells, and the death and survival of neurons. The hippocampus
      is prominent in these effects, and it also displays the highest level of Type I
      receptors of any brain region. New concepts point to a special role of the
      hippocampus, a nexus of cognition and emotion, in the feedback actions of adrenal
      steroids during the diurnal rhythm, and in response to stress. The hippocampus
      is, therefore, a prime target area for investigation of the events which
      accompany stress, and which may be related to the maladaptive state that results
      in depressive illness. Initial studies are described which investigate the
      effects of tianeptine on pituitary-adrenal function, hippocampal morphology and
      Type I and Type II receptor levels.

PMID- 1389023
TI  - Neurochemical and pharmacological properties of tianeptine, a novel
      antidepressant.
AB  - Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a
      long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and
      with biochemical and animal-behavioural properties which are strikingly different
      from those of classical tricyclics. Unlike the latter, which decrease serotonin
      (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat
      brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the
      depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases
      rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite
      effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens
      the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other
      tricyclics prolong it, and it enhances attention, learning, and memory in
      laboratory animals, while classical tricyclics have opposite effects. However,
      the relationships between these effects of tianeptine in animal experiments and
      their relevance to clinical findings remain to be determined.

PMID- 1389024
TI  - Long-term use of tianeptine in 380 depressed patients.
AB  - Tianeptine is a new tricyclic compound whose principal action is to increase the
      reuptake of serotonin. In a multicentre trial in which 380 depressed patients
      were treated for one year, tianeptine produced a significant reduction in the
      MADRS scores from day 14, with a sustained reduction maintained for up to 12
      months; other measures of efficacy (HRSA, HSCL, and CGI) also reflected the
      improvement. Only 11% of patients withdrew because of recurrence of depression
      and 2% because of side-effects, which were mainly drowsiness, irritability, and
      gastrointestinal disturbance. Apart from a minor reduction in heart rate,
      unaccompanied by any conduction changes, no clinically relevant changes in vital
      signs or laboratory tests were seen. Seven subjects who attempted suicide by
      tianeptine overdose had favourable outcomes, in spite of also taking other
      psychotropic drugs or alcohol. No evidence of tolerance or withdrawal symptoms
      was seen after treatment was stopped. These results suggest that tianeptine has
      the potential to provide safe antidepressant activity in both the acute and
      chronic phases of treatment.

PMID- 1389025
TI  - Long-term administration of tianeptine in depressed patients after alcohol
      withdrawal.
AB  - Alcohol interferes with the central metabolism of the catecholamines and
      especially with indolamines (5-HT). Thus, the use of an antidepressant such as
      tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT,
      seems to be particularly indicated for the continued treatment of depressed
      patients after alcohol withdrawal. This study evaluated the therapeutic efficacy
      and acceptability during long-term administration of tianeptine in depressed
      patients (major depressive episode or dysthymic disorder) in a multicentre trial,
      after withdrawal from alcohol abuse or dependence. The results relate to 130
      depressed patients, who abstained from alcohol and received treatment for a year.
      Only one patient dropped-out because of side-effects, and medication was
      interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the
      long term, tianeptine did not produce orthostatic hypotension, changes in
      bodyweight, or alterations in the ECG. All changes found in haematological and
      biochemical investigations suggested an improvement in patients' physical state.
      This, and other studies, indicate that tianeptine appears to have the potential
      to be a safe antidepressant, which might be particularly useful in those patients
      who are susceptible to the side-effects of psychotropic drugs.

PMID- 1389027
TI  - Relationship between the neuroses and brief reactive psychosis: descriptive case
      studies in Africa.
AB  - Predominant psychopathology in a selected population group--adolescents and young
      adults at school--in a developing country, is described. The highly selective
      referral to services was supplemented by active case finding in the community
      over three years. There were 54 cases of somaticised anxiety (brain fag); 22
      cases of depressive neurosis characterised by hypochondriasis, cognitive
      complaints, and culturally determined paranoid ideation; 23 cases of 'hysteria'
      in the form of dissociative states, pseudoseizures and fugues; and 39 cases of
      brief reactive psychosis which differed from the dissociative states more in
      duration and intensity than in form. There was a temporal relationship between
      transient psychosis and the school calendar. Anxiety or depression often predated
      the florid psychotic reaction which served as a form of help-seeking behaviour or
      defence in intolerable stress.

PMID- 1389026
TI  - Efficacy of tianeptine in comparative trials versus reference antidepressants. An
      overview.
AB  - The clinical properties of tianeptine have been assessed in double-blind
      controlled studies, which involved depressed patients fulfilling DSM-III criteria
      for either major depression--single episode or recurrent (without melancholia and
      psychotic features)--or dysthymic disorder--with or without an additional
      diagnosis of alcohol abuse or dependence. Five studies have compared tianeptine
      with reference antidepressants: its efficacy has been found to be similar to that
      of amitriptyline in depressed out-patients. However, these data need to be
      confirmed by other controlled trials v. reference drugs and by at least two
      placebo-controlled studies. Tianeptine does not induce sleep disorders,
      anticholinergic effects, or modifications of cardiovascular variables or
      biological parameters (renal, haematological, or hepatic). After the end of
      treatment, the only signs of withdrawal have been some disturbances of sleep.

PMID- 1389029
TI  - Patterns of mental illness in the early stages of urbanisation. Introduction.

PMID- 1389028
TI  - Brief reactive psychosis and the major functional psychoses: descriptive case
      studies in Africa.
AB  - In a three-year prospective study of service-based incidence of functional
      psychoses in Africa, 94 cases of brief reactive psychosis were compared with 56
      cases of schizophreniform syndromes, 29 cases of DSM-III schizophrenia and 14 of
      manic-depressive psychosis. This was supplemented by retrospective study of the
      same syndromes not in their first episode. Brief reactive psychosis was found to
      be a composite syndrome. The 50% with preceding depression were a distinct group,
      in terms of course and demographic features. Of those with intense prodromal
      anxiety, most were a single episode precipitated by a major life event, a few
      showed a recurrent long-term pattern. Schizophrenia was heralded, or presented
      unequivocally months or years later, in 10-20%. The schizophreniform group
      comprised a range of atypical psychoses intermediate between the transient and
      major psychoses. The pattern of precipitants and the over-representation of
      education and paid employment in the acute syndromes, compared with the major
      psychoses, in a society which was largely first-generation educated, suggested a
      link with rapid social change.

PMID- 1389030
TI  - Profile and prevalence of the brain fag syndrome: psychiatric morbidity in school
      populations in Africa.
AB  - The profile and prevalence of a syndrome of somaticised anxiety associated with
      education in Africa was explored by survey of 2040 senior secondary school
      students in different types of school: rural, urban, and elite. Response to two
      different screening methods, an open question to elicit symptoms spontaneously,
      and the SRQ-24, was compared. Symptom prevalence was higher in rural schools,
      34%, than periurban, 22%, and elite, 6%, but the central urban school serving a
      shanty town was also high at 35%. Three categories of the culturally relevant
      symptoms were identified--somatic, cognitive and 'spiritual'--with affective
      symptoms sparsely represented in the cultural idiom. The SRQ-24 items screening
      for psychosis were associated with a range of spontaneous symptoms representing
      anxiety. This 'spiritual' expression of neurosis reflects the world views and
      beliefs of the culture. Intensification under stress could produce the picture of
      transient reactive psychosis.

PMID- 1389031
TI  - Social origins of the brain fag syndrome.
AB  - The aetiology of psychiatric morbidity associated with education in Africa was
      explored using two different screening methods (as described in paper III, this
      supplement). The interactive effect of psychosocial variables was examined by Log
      linear analysis which demonstrated five independent factors: (a) the financial
      implications of education which represented the change from subsistence to cash
      economy; (b) fear of envy and bewitchment which represented the intense cultural
      response to education; (c) parenting in the pre-school years which was the
      independent family variable; (d) academic ability; (e) attributes of the school.
      Age of starting school and birth rank had a marginal effect. Current family
      adversity in terms of unstable parental union, paternal use of alcohol, polygamy
      and sibship size operated by interactive or additive effect. Gender and social
      status had no effect. The brain fag syndrome can be related to the complex social
      changes during rapid social transition where education is a major agent of
      change.

PMID- 1389032
TI  - A call for partnership between schizophrenic patients, relatives and
      professionals.

PMID- 1389033
TI  - Stress-indicative patterns of non-verbal behaviour. Their role in family
      interaction.

PMID- 1389034
TI  - Assessment of coping with schizophrenia. Stressors, appraisals, and coping
      behaviour.

PMID- 1389036
TI  - Providing schizophrenic patients with a concept of illness. An essential element
      of therapy.

PMID- 1389035
TI  - Coping style and cognitive dysfunction in schizophrenic patients.

PMID- 1389037
TI  - Biological and cognitive vulnerability factors in schizophrenia: implications for
      treatment.

PMID- 1389038
TI  - The person-key to understanding mental illness: towards a new dynamic psychiatry,
      III.

PMID- 1389039
TI  - Chronicity in schizophrenia: revisited.

PMID- 1389040
TI  - Course of illness and predictors of outcome in chronic schizophrenia:
      implications for pathophysiology.

PMID- 1389041
TI  - Comparison of long-term outcome of schizophrenic, affective and schizoaffective
      disorders.

PMID- 1389042
TI  - Implications of adoption studies on schizophrenia.

PMID- 1389043
TI  - Childhood attentional dysfunctions predict social deficits in unaffected adults
      at risk for schizophrenia.

PMID- 1389044
TI  - Non-verbal behavioural dysfunction in schizophrenia. Vulnerability indicator,
      residual marker or coping strategy?

PMID- 1389045
TI  - Cancer incidence of schizophrenic patients. Results of record linkage studies in
      three countries.

PMID- 1389046
TI  - The triggering hypothesis of the role of life events in schizophrenia.

PMID- 1389047
TI  - Paths to relapse: possible transactional processes connecting patient illness
      onset, expressed emotion, and psychotic relapse.

PMID- 1389048
TI  - Family interaction versus individual psychopathology. Do they indicate the same
      processes in the families of schizophrenics?

PMID- 1389049
TI  - Four-quadrant cricoid cartilage division in laryngotracheal reconstruction.
AB  - Four-quadrant division of the cricoid cartilage is a relatively new technique of
      laryngotracheal reconstruction. Division of the lateral walls of the cricoid
      cartilage, with or without placement of autogenous cartilage grafts, allows for
      increased expansion of the subglottic lumen. Between October 1, 1986, and January
      1, 1990, 185 laryngotracheal reconstructions were performed at our institution.
      During that time, 31 four-quadrant division laryngotracheal reconstruction
      procedures were performed in 29 patients (mean age at surgery, 5 years 5 months).
      Grade 3 or 4 laryngeal stenosis existed preoperatively in 72% (22/31) of cases.
      The initial decannulation rate after four-quadrant division laryngotracheal
      reconstruction was 58% (18/31). Of 11 patients requiring revision surgery after
      four-quadrant division laryngotracheal reconstruction, four were eventually
      decannulated, for an overall decannulation rate of 76% (22/29). The indications,
      technique, results, and potential complications of four-quadrant division of the
      cricoid cartilage in laryngotracheal reconstruction are discussed.

PMID- 1389050
TI  - Gastropharyngeal reflux in infants and children. A pharyngeal pH monitoring
      study.
AB  - Gastroesophageal reflux has been shown to play an important role in chronic and
      acute inflammatory disorders of the airway. In particular, gastroesophageal
      reflux has been suggested to be the cause of pharyngolaryngeal problems,
      according to the literature, at any age. However, to our knowledge, the presence
      of acid in the pharynx in pathological cases has not yet been proved. A series of
      eight patients (aged 2 months to 7.5 years) with recurrent acute
      laryngotracheitis underwent a two-channel pH monitoring for 23 to 24 hours. One
      pH probe was placed in the lower esophagus, the other in the pharynx, at the
      level of the epiglottis. Acid gastroesophagopharyngeal reflux was demonstrated in
      every patient. A significant difference with a series of six control subjects was
      noted in terms of esophageal and pharyngeal pH monitoring. The most significant
      item is the total time the pH in the pharynx was below 6. Despite the limited
      number of patients, this study suggests the role of gastroesophageal reflux in
      recurrent laryngotracheitis in infants and children.

PMID- 1389051
TI  - Chemosensitivity and DNA ploidy in head and neck squamous cell carcinomas.
AB  - The succinate dehydrogenase activity and cellular DNA content of human head and
      neck squamous cell carcinomas were examined, and the chemosensitivity and ploidy
      status were compared with histologic differentiation. The average decrease of
      enzyme activity in the poorly differentiated squamous cell carcinomas was
      significantly greater than that of well- and moderately differentiated squamous
      cell carcinomas. Statistically significant differences were also noted with
      relation to the original site of the primary tumor. The chemosensitivity of a
      tumor with DNA aneuploidy tended to be lower among the well- and moderately
      differentiated squamous cell carcinomas and higher among the poorly
      differentiated type. We conclude from this study that simultaneous analysis of
      the chemosensitivity and DNA ploidy will aid not only in selecting effective
      antitumor drugs but also in predicting changes in cellular characteristics during
      the course of disease.

PMID- 1389052
TI  - Postoperative radiation-associated changes in free jejunal autografts.
AB  - Free jejunal autografts are a preferred method of pharyngoesophageal
      reconstruction. Ten adult mongrel dogs underwent free jejunal transplantations to
      the neck, five being controls and five receiving a 55-Gy equivalent dose of
      radiation after 3 weeks. Histologic changes 10 months after radiotherapy included
      simplified and blunted villi with normal architecture loss; fibrous replacement
      of the lymphatics and microvasculature in the intravillous space; goblet cell
      increase; significant increase in lamina propria thickness and muscularis mucosa
      fibrous plates; focal destruction and replacement of muscle layers with fibrosis;
      gross hypertrophy of the myenteric plexus with increased fibrous tissue about the
      hypertrophied neural tissue; and significant perivascular fibrosis. Controls
      demonstrated only minimal changes. These adverse delayed effects of irradiation
      on revascularized jejunal autografts should be considered in planning the method
      of pharyngoesophageal reconstruction as well as timing of adjuvant radiotherapy.

PMID- 1389053
TI  - Monitoring of revascularized jejunal autografts.
AB  - Free jejunal autografts have been widely used to reconstruct circumferential
      pharyngeal defects in a single stage. Close postoperative monitoring of the
      perfusion of the free jejunal autograft is extremely important in achieving a
      successful outcome. Presented herein is our method of postoperative monitoring of
      jejunal autografts in which a segment of jejunum pedicled on its connecting
      mesentery is exteriorized. This method of monitoring was performed in 17 cases,
      and there were no cases of late graft failure. Of three patients who had
      undergone this operation before the use of this monitoring technique, one had an
      unrecognized late graft failure. We present our experience with this simple and
      reliable method to monitor free jejunal autografts.

PMID- 1389054
TI  - Head and neck liposarcoma. A histopathologic reevaluation of reported cases.
AB  - Head and neck liposarcoma is an extremely rare tumor. As with all rare lesions
      there is a void in the literature regarding tumor activity and treatment
      response. It is difficult to make rational treatment plans and advise patients as
      to probable treatment response and prognosis. To obtain as much information as
      possible from available data we have reviewed the world literature and
      reevaluated the descriptive histopathologic findings and treatment response of
      reported cases. Seventy-six cases have been reported since 1911. We added another
      case and then reclassified the previously reported lesions according to a current
      histopathologic system (well-differentiated, myxoid, round-cell, and pleomorphic
      lesions). We assessed tumor activity and treatment response by histopathologic
      tumor type. Paralleling tumor activity in other anatomic regions, all patients
      with myxoid and well-differentiated tumors did well; all were alive at the end of
      follow-up, eight of eight and 11 of 11, respectively (average follow-up, 5.7 and
      4.8 years). This is compared with a 50% mortality rate in the round-cell and
      pleomorphic groups by the end of 2 years, (two of three and six of 11 patients
      alive, respectively). The likelihood of recurrence correlated with extent of
      tumor removal, and metastatic disease was identified almost exclusively with the
      tumor of the round-cell and pleomorphic variants. Surgical excision remains the
      primary treatment modality, while radiation and chemotherapy appear to be of
      limited utility.

PMID- 1389055
TI  - The influence of intensive hyperbaric oxygen therapy on skin flap survival in a
      swine model.
AB  - Conflicting reports exist regarding the influence of hyperbaric oxygen therapy on
      random skin flap survival. The present investigation sought to demonstrate
      enhanced survival of experimental random skin flaps in swine using an intensive
      and tapering hyperbaric oxygen therapy regimen that would have direct application
      in human clinical trials. Random cutaneous flaps were surgically constructed on
      12 domestic pigs. Flaps were designed to obtain a predictable length of necrosis.
      Six pigs did not undergo hyperbaric oxygen therapy and served as surgical
      controls. Six pigs were subjected to an intensive tapering hyperbaric regimen
      within 1.5 hours of completing the surgical procedure. Treatments were
      administered in a research hyperbaric vessel at a depth of 2.0 atm absolute (10 m
      of seawater) for 90 minutes of oxygen treatment in a tapering schedule over 6
      days. This was structured to provide intensive therapy initially during the
      period of maximum tissue trauma and ischemia. Extent of flap necrosis was
      assessed by tracing clear plastic templates at necropsy, then converting to
      square centimeters using a computer digitizer tablet. The difference in flap
      necrosis between groups was significant, with random flaps subjected to
      hyperbaric oxygen therapy demonstrating a mean 35% less necrosis than surgical
      controls. Skin flaps treated with hyperbaric oxygen therapy demonstrated a mean
      survival of 77%, with a range of 56% to 100%. This reflected a 12% improvement in
      mean surviving area for hyperbaric oxygen therapy flaps over untreated surgical
      controls. We are unaware of similar studies reporting a comparable degree of
      enhancement in random skin flap survival using hyperbaric oxygen therapy alone.
      Adjunctive hyperbaric oxygen therapy in an intensive tapering schedule
      significantly improved flap survival in this model. Further investigations need
      to determine the optimum frequency of treatments and depth necessary to attain
      maximum tissue viability.

PMID- 1389056
TI  - Middle fossa vestibular neurectomy in retrolabyrinthine neurectomy failures.
AB  - Retrolabyrinthine vestibular nerve section is an important treatment option in
      patients with refractory, incapacitating vertigo. However, an indistinct cleavage
      plane between the cochlear and vestibular portions of the eighth cranial nerve
      may result in incomplete sectioning of the superior and inferior vestibular nerve
      fibers. We describe 11 patients in whom middle fossa vestibular neurectomy was
      performed following failure of a retrolabyrinthine vestibular neurectomy. A
      successful postoperative outcome from this revision surgery was obtained in six
      of 11 patients on follow-up evaluation. Patients in whom infrared video
      electronystagmography showed persistent function of the inferior vestibular nerve
      following retrolabyrinthine vestibular nerve section had a better response to
      middle fossa vestibular neurectomy than those with no measurable residual
      vestibular function. Because it provides access to the vestibular nerves where
      there is separation from the cochlear nerves distal to the previous section, we
      feel that the middle fossa vestibular neurectomy is the procedure of choice in
      selected patients who fail retrolabyrinthine neurectomy.

PMID- 1389057
TI  - Some aspects of life quality after surgery for acoustic neuroma.
AB  - This investigation was performed to describe some aspects of the quality of life
      in subjects after translabyrinthine removal of an acoustic neuroma, resulting in
      unilateral total deafness. Two hundred ninety-three subjects who had been
      operated on during 1976 through 1990 and who were living outside the Copenhagen
      (Denmark) City and County received a postal questionnaire, to which 93% (n = 273)
      responded: 118 men and 155 women with a median age of 58 years (range, 18 to 81
      years). The median observation period from surgery to the questionnaire was 6
      years (range, 6 months to 14 years), and the median age at operation was 52 years
      (range, 15 to 76 years). Among the subjects, 22% had received postoperative
      hearing rehabilitation with various types of hearing aids in the ear not operated
      on. In 62%, tinnitus was experienced in the ear with tumor before surgery, and at
      the time of the questionnaire, 49% experienced tinnitus in the ear operated on.
      Half a year after surgery, 56% still experienced dizziness. Sixty-four percent
      reported damage to the facial nerve in relationship to the operation. At the time
      of the questionnaire, 12% indicated a total loss of facial nerve function. No
      vocational consequences were found in 74% after surgery. Information concerning
      different symptoms related to surgery was insufficient in 29%, while the quality
      of information in relation to surgery was more satisfying. In conclusion, the
      study demonstrates that deafness, dysequilibrium, and reduced facial nerve
      function caused the most severe problems. Improved information to patients before
      surgery may reduce the frequency of negative experiences.

PMID- 1389058
TI  - Distortion-product otoacoustic emissions. Values for clinical use.
AB  - Distortion-product otoacoustic emissions are otoacoustic emissions evoked by two
      pure tones. They are proposed as a frequency-specific test of the mechanical
      properties of the cochlea. The aim of this study was to measure distortion
      product otoacoustic emissions in a clinical setting to establish the most
      interesting values suitable for clinical use and the clinical interest of the
      method. The statistical analysis of the data points out some clinically
      interesting values: (1) a screening limit value of 30 dB hearing level and when
      measuring distortion-product otoacoustic emissions in response to 52 dB sound
      pressure level for studying active frequency selective mechanisms; (2) a
      screening limit value of 50 dB hearing level and when measuring distortion
      product otoacoustic emissions in response to 72 dB sound pressure level for
      studying passive cochlear mechanisms; and (3) the slope of the input-output
      function. All physiologic properties of the cochlea fit with these basic
      distortion-product otoacoustic emission properties. These criteria can be used
      whatever the population studied and the material used for distortion-product
      otoacoustic emissions recordings. Distortion-product otoacoustic emissions can be
      used as a screening test to separate (1) subjects with normal hearing and
      subjects with a hearing threshold above 30 dB hearing level (distortion-product
      otoacoustic emissions in response to a 52 dB sound pressure level "primaries"
      [ie, pure tones] stimulation intensity), and (2) patients with a hearing
      threshold above or below 50 dB hearing level (distortion-product otoacoustic
      emissions in response to a 72 dB sound pressure level primary stimulation
      intensity). Distortion-product otoacoustic emissions cannot be used as a more
      precise audiometric test.

PMID- 1389059
TI  - Three-component analysis of caloric nystagmus in humans.
AB  - Three-component analysis of caloric nystagmus, focusing on the horizontal,
      vertical, and torsional, using a computerized eye movement analysis system, was
      carried out in 10 normal human subjects. The caloric response was induced by cold
      stimulation to the right ear of the subjects in the supine and prone positions.
      In the supine position, the three components of nystagmus were toward the left
      (10 subjects), upward (eight subjects) or downward (two subjects), and clockwise
      (10 subjects). In the prone position, on the other hand, the three components
      were directed toward the right (10 subjects), downward (five subjects), upward
      (three subjects), and counterclockwise (10 subjects); there was no vertical
      direction in two subjects. These findings indicate that caloric stimulation
      activates the three semicircular canals simultaneously. Also the changes in the
      nystagmus direction in the supine and prone positions could be explained, at
      least partially, by the nonconvective component of caloric stimulation.

PMID- 1389060
TI  - Lateral arm free flap in head and neck reconstruction.
AB  - The lateral arm fasciocutaneous free flap is a versatile donor site of sensate
      soft tissue for reconstruction and augmentation of the head and neck. The lateral
      arm flap can be quickly harvested without interference to the head and neck team
      and with minimal morbidity to the patient. For these reasons, this flap has
      become our soft-tissue flap of choice.

PMID- 1389061
TI  - Extended access/internal approaches for the management of facial trauma.
AB  - The two most significant recent developments in the treatment of facial trauma
      are the introduction of plating systems, which provide rigid internal fixation
      and the development of surgical approaches that allow wide exposure of the entire
      facial skeleton while minimizing external incisions. These approaches (referred
      to as extended access/internal approaches) are hemicoronal and coronal flaps, the
      sublabial approach to the midface, the transconjunctival approach to the orbital
      floor and orbital rim, and the intraoral management of mandibular fractures.
      These approaches work well, and have become standard techniques for managing
      facial trauma; however, each one has definite technical points that need to be
      adhered to to assure their success. Additionally, there are situations where
      these approaches are not appropriate and, in fact, may even be detrimental. This
      article outlines our approach to facial trauma using these extended
      access/internal approaches and discusses the important technical factors of each
      approach. Our experience in treating 113 patients with 119 fractures and 161
      approaches over the last 2 years is presented and the role extended
      access/internal approaches have played is reviewed. The indications, limitations,
      and possible complications associated with each approach are outlined.

PMID- 1389062
TI  - Hiccups. A case presentation and etiologic review.
AB  - Hiccups (singultus) usually present as a common annoyance lasting for short
      periods. Rarely, they may be the harbinger of a serious disease. We present the
      case of a 19-year-old man in which intractable hiccups was the first and most
      prominent symptom of a serious underlying neurologic disorder. The patient had
      been examined by his pediatrician, and despite multiple medical regiments and
      physical maneuvers, his symptoms persisted. A thorough head and neck examination
      revealed a right-sided vocal cord paralysis. This finding prompted obtaining a
      magnetic resonance imaging scan, which demonstrated a type I Arnold-Chiari
      malformation associated with a large cervicothoracic syringomyelia. The patient
      was referred to the neurosurgical service and subsequently underwent a
      ventriculoperitoneal shunt placement. There was considerable initial improvement
      in his neurologic status and cessation of the hiccups. However, the symptoms
      recurred within 1 month. The case report as well as a brief review of the
      relevant pathophysiologic and etiologic considerations and several treatment
      modalities for hiccups is presented.

PMID- 1389063
TI  - Autoantibodies against constituents of neutrophils in the diagnosis and treatment
      of (isolated) subglottic stenosis.
AB  - Six patients had a subglottic stenosis either as a presenting symptom or as a
      manifestation of a systemic disease. All patients had in common the presence of
      circulating autoantibodies against constituents of neutrophils on indirect
      immunofluorescence. Cytoplasmic and perinuclear staining patterns were
      recognized. Such autoantibodies have been reported in Wegener's granulomatosis,
      microscopic polyarteritis, (idiopathic) glomerulonephritis, and Churg-Strauss
      syndrome. However, only one of the six patients fulfilled the criteria for these
      conditions. Because a positive test for autoantibodies against constituents of
      neutrophils is rare in other conditions and because other diseases had been
      excluded, we suggest that this places subglottic stenosis within the spectrum of
      necrotizing (granulomatous) vasculitis. The consequences for therapy are
      discussed.

PMID- 1389065
TI  - Pathologic quiz case 1. Auricular pseudocyst (benign idiopathic cystic
      chondromalacia, endochondral pseudocyst, or seroma of the auricle).

PMID- 1389064
TI  - Magnetic resonance imaging of the large vestibular aqueduct.
AB  - The large vestibular aqueduct syndrome describes an abnormally large
      endolymphatic duct and sac with associated sensorineural hearing loss. This
      entity was originally reported in 1978 and has since been identified as a finding
      in children with progressive hearing loss. The original description of the large
      vestibular aqueduct employed hypocycloidal polytomography of temporal bone.
      Subsequent reports studied patients identified with this syndrome using computed
      tomographic scans. We report magnetic resonance imaging of two patients diagnosed
      with the large vestibular aqueduct syndrome. The magnetic resonance imaging and
      computed tomographic scans are compared and the significant findings on magnetic
      resonance imaging are reviewed. This should assist the otolaryngologist and
      radiologist with establishing the appropriate diagnosis.

PMID- 1389066
TI  - Pathologic quiz case 2. Psammomatoid (juvenile) ossifying fibroma (POF) of the
      ethmoid sinus.

PMID- 1389067
TI  - A few bad apples...

PMID- 1389068
TI  - Computerized prescription writing in otolaryngology.

PMID- 1389069
TI  - Nasal polyps: a sign of disease.

PMID- 1389070
TI  - [Effect of various heavy metals on the ATP content of spermatozoa from Arbacia
      lixula L.--activity of mercury].
AB  - This work reports the evaluation of some toxic effects induced by mercury on sea
      urchin sperm. Spermatozoa of the sea urchin Arbacia lixula L., were treated with
      0.003, 0.03 and 0.06 mg/l of Hg. We estimated the amount of ATP of sperm cells
      with the luciferin-luciferase reaction, and we also observed motility,
      fertilizing activity and number of sperm bound to the eggs. The results clearly
      show that ATP levels are strongly affected by mercury concentrations, already
      three hours after the beginning of treatment. We propose the use of ATP
      determination in sea urchin sperm as a bioassay, because they, even more than
      eggs and developmental stages, readily suffer the environmental stresses.

PMID- 1389071
TI  - Functional properties of dilute Hb solutions studied without tonometric
      techniques.
AB  - The authors found that, by continuously bubbling pure nitrogen within a dilute Hb
      solution, the latter releases its oxygen with an intensity which is quite
      proportional to the duration of bubbling. Such a procedure can be employed
      instead of the common tonometric technique, to measure functional properties of
      Hb. In fact, not only dissociation curves can be obtained, but also a correct
      evaluation of the affinity changes upon pH variations (Bohr effect). The results
      obtained by this technique are not far from those recently reported by using
      tonometry, although the method is less precise and still not suitable for routine
      purposes. Nevertheless, it can be substantially improved.

PMID- 1389072
TI  - Functional behaviour of dilute solutions of Hb-Kempsey: beta 99 (G-1) Asp--Asn.
AB  - The authors report that a diluted solution of Hb-Kempsey, beta 99 (G-1) Asp-Asn,
      can be chromatographically separated from the coexistent Hb-A and functionally
      examined if progressively depleted in O2 by bubbling pure nitrogen in the
      solution. Next, at fixed times, the O2 saturations of Hb are compared with the
      pO2s measured. Hb-Kempsey has a p50 of 1 torr, with an n-value of 1 and a Bohr
      effect of -0.2. Normal Hb-A of the same patient, examined with identical methods,
      presents: p50 = 4.5 torr; n = 2.7; Bohr effect = -0.412. Therefore, Hb-Kempsey is
      strongly hyperaffinic, does not display any heme-heme interaction, and has a half
      normal Bohr effect.

PMID- 1389073
TI  - [Correlation of the clinical phenotype with a pericentric inversion of chromosome
      9].
AB  - Pericentric inversion of chromosome 9 is one of the most common structural
      balanced chromosomal aberrations. It is considered as a paraphysiological variant
      of a normal karyotype and it is possible to find it as occasional report in
      healthy subjects. In the last ten years different signals have appeared in
      literature, concerning carriers of pericentric inversion of chromosome 9, who
      showed different anomalies of the clinical condition. Today it is difficult,
      because of the rarity of the data to establish if a true correlation exists
      between phenotypical anomalies in the subjects studied and the pericentric
      inversion, or if they are only casual associations. We are trying to find
      possible correlations between the chromosomal rearrangements and eventual
      congenital defects. We describe 11 subjects with pericentric inversion of
      chromosome 9 examined for the presence of dysmorphic signs, mental retardation
      and repeated miscarriage.

PMID- 1389074
TI  - [Familial segregation of simple and complex chromosomal rearrangements].
AB  - We report our observations about familial segregations of chromosomal
      aberrations: the simple forms and complex rearrangements. Congenital
      malformations and mental retardation, can be present both in unbalanced and in
      balanced translocations. Various hypotheses have been proposed to explain this
      phenomenon: in particular a possible "position effect" or genic mutation or
      genomic imprinting. In our study we have used both standard techniques and
      techniques with high resolution banding to investigate if the rearrangements were
      balanced or not. Molecular study and gene dosage have been used when possible, to
      define the correlation with the clinic phenotype.

PMID- 1389075
TI  - Silent cholinesterase gene: three homozygotes in a small Caucasian population.
AB  - Three sera, showing only a 2-3% of the usual cholinesterase activity and
      belonging to two families of 800 Caucasian inhabitants of the same small town,
      were classified as type II silent cholinesterase genes by polyacrylamide slab gel
      electrophoresis, dibucaine and fluoride number and by their specific activity
      with acetyl- butyryl- or propionyl-thiocholine.

PMID- 1389076
TI  - [Interaction between vision and vestibular nystagmus].
AB  - In order to assess the visuo-vestibular interaction and its behaviour in
      connection with the age, we have submitted 20 healthy subjects from two age
      groups ranging between 21-30 and 65-75 years of age to two rotation tests (with
      closed eyes and with opened eyes with fixation of a light). The results show a
      variation of the nystagmic response with fixation of about 60% in the young
      people and of about 40% in the elderly. These results demonstrate that the extent
      of the inhibition is dependent upon age and is less effective in the elderly.

PMID- 1389078
TI  - [Evoked acoustic oto-emissions in cochlear deafness].
AB  - In order to give a contribution to the genesis of the EOAEs, we have recorded
      echos in 24 subjects with unilateral sudden deafness (I. group); 20 ears with
      Meniere disease (II. group); 22 ears with progressive sensorineural hearing loss
      (III. group) and 10 normally hearing young subjects as control group. The results
      have shown that the EOAEs were present in 100% (I. group), 84.6% (II. group) and
      86.3% (III. group) in response to the tone-burst; while the echos were present
      only in the 57.1% (I. group), 38.4% (II. group) and 45.4% (III. group) in
      response to the click, although the audiometric threshold mean were greater than
      45 dB HL for 2-4 KHz and 1 KHz in the three experimental groups except for 2-4
      KHz in the subjects with Meniere disease (37.5 dB HL). The properties of EOAEs
      (detection and saturation threshold, dynamic range and duration) depended on the
      degree of hearing loss. Our results seem to corroborate the hypothesis that EOAEs
      could be also produced by a passive intracochlear mechanism attributable to the
      travelling wave of the basilar membrane provoked by the perilymph. In the normal
      ear this passive mechanism could be superimposed by an active mechanism, linked
      to the contractile activity of the outer hair cells with a consequent increase in
      amplitude of the EOAEs for the same stimulus intensity.

PMID- 1389077
TI  - [Brain-stem auditory pathways: effects of atropine].
AB  - The efferent pathways exert a control action on the function of the cochlear
      nucleus and hair cells. Acetylcholine is the neurotransmitter of the centrifugal
      system and its action can be blocked by Atropine. In order to give a contribution
      to the knowledge of the function of the efferent bundle, Auditory Brainstem
      Responses (ABRs) and Acoustic Reflex Latencies (ARLs) have been examined in 10
      young normal subjects there was also a decrease in latency greater than or equal
      to 100 microseconds by at least other two waves. The only statistically
      significant difference was relative to the latency mean value of the wave III
      recorded in contralateral derivation at 11 pps. The ARLs, after the infusion of
      atropine, showed a statistically significant increase in 7 of the 10 cases; no
      change was recorded in the AR amplitude. It can be concluded that the
      pharmacological block of the olivo-cochlear bundle determines a delay in the
      neural conduction of the acoustic impulses; this finding means that the atropine
      can inhibit the facilitating activity of the efferent system on the brainstem
      afferent pathways.

PMID- 1389079
TI  - Alzheimer disease brain extract stimulates branching of laminin-mediated neuronal
      processes.
AB  - Patients with Alzheimer disease (AD) suffer mental deterioration associated with
      neurofibrillary tangle and senile plaque formation in the brain. Here we have
      determined the effects of brain extracts from normal and from AD patients on
      neuronal process formation by a pheochromocytoma (PC-12) and a neuroblastoma x
      glioma hybrid cell line (NG108-15). PC12 cells show a dose-related stimulation of
      branching of neuronal processes by AD brain extracts with cells cultured on a
      laminin substrate. The neurotrophic effects of extracts of AD brains may be
      related to the abnormal sprouting and neurofibrillary tangle formation observed
      in the brain in this disorder.

PMID- 1389080
TI  - DSM-III-R criteria for primary degenerative dementia and multi-infarct dementia
      [corrected].
AB  - Primary degenerative dementia (PDD) and multi-infarct dementia (MID) are the two
      most common categories of cognitive decline in old age. The definitions of these
      two clinical entities are currently based on clinical evaluation and on the
      exclusion of other underlying causes, and still lack a consensus. The DSM-III-R
      criteria are widely used for the diagnosis of dementia. However, their role in
      the differentiation between PDD and MID has not been thoroughly examined. A
      consecutive series of 98 demented patients who met the DSM-III-R criteria for
      dementia were admitted to a clinical study. Upon evaluating their type of
      dementia according to these criteria, 53 patients could not be diagnosed either
      as having PDD or MID. The DSM-III-R criteria for these two types of dementia are
      critically reviewed. Proposed modifications, aimed at refining their differential
      diagnostic role, are presented, enabling better allocation of demented patients
      into PDD, MID, or intermediate groups.

PMID- 1389081
TI  - Behavioral symptoms in Alzheimer disease: a look ahead.

PMID- 1389082
TI  - Behavior control and Alzheimer disease in perspective.

PMID- 1389083
TI  - Management of behavior disturbance in Alzheimer disease: current knowledge and
      future directions.
AB  - Assessment and treatment of behavior problems in patients with Alzheimer disease
      and related disorders is a seriously neglected area of study. Despite the fact
      that such problems are integral to the disorder, little is known about effective
      management. This article summarizes the current thinking on five areas of prime
      importance to patients, care providers, and health care professionals: agitation,
      assault/aggression, screaming, wandering, and depression/apathy/withdrawal.
      Methodological guidelines for studying these disorders are provided. Emphasis is
      on recognizing that behavior problems are important areas of study in their own
      right as well as in conjunction with studies of cognition.

PMID- 1389084
TI  - Alzheimer disease assessment scale: useful for both early detection and staging
      of dementia of the Alzheimer type.
AB  - The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 patients
      with dementia of the Alzheimer type (DAT) and 52 elderly controls. The DAT group
      was subdivided into different severity levels of dementia based on scores from
      the Mini-Mental State Exam: very mild (greater than or equal to 24), mild (20 to
      23), moderate (10 to 19), and severe (0 to 9). The mean scores on the ADAS
      Cognitive subscale for the four levels of dementia (very mild = 23.1 +/- 7.7,
      mild = 22.9 +/- 8.9, moderate = 38.6 +/- 9.8, severe = 54.8 +/- 7.6) were
      statistically different from one another (p less than 0.0001, except very mild
      vs. mild) and were significantly worse than the scores of the elderly control
      group (5.5 +/- 2.7, p less than 0.0001, ANOVA). Furthermore, the ADAS Cognitive
      subscale was highly effective in discriminating individual Alzheimer patients
      from elderly controls. The ADAS Cognitive score correctly classified 100% of the
      very mild group, 91% of the entire mild group, and 100% of the moderate and
      severe groups when a cutoff score of 2 SDs above the control group mean was used.
      Age and education had only minimal effects on the ADAS Cognitive score. The ADAS
      is a valuable screening test that only takes 30 min to administer and has utility
      in both early detection and staging of DAT.

PMID- 1389085
TI  - Seventy years of insulin: where are we now?

PMID- 1389086
TI  - Evaluation of growth hormone secretion and treatment.
AB  - The secretion of growth hormone (GH) is regulated by a complex system that
      includes both neurotransmitters and feedback by hormonal and metabolic
      substrates. Over the last few years it has been recognized that GH release varies
      over a wide spectrum from deficient to excessive secretion. The diagnosis of GH
      deficiency is based on a combination of anthropometric and clinical signs on the
      one hand and an inadequate stimulated and/or spontaneous GH secretion on the
      other. There is no distinct boundary between deficient and sufficient GH
      secretion. The cut-off limit for normal GH release is accordingly relative and
      has increased over the past decade from 5 to 10 micrograms/l. The effect of GH
      therapy on growth can be evaluated only after treatment for at least 6 months.
      There is, therefore, an indisputable need for methods that would reflect growth
      response soon after the start of treatment. There are several promising
      biochemical candidates, e.g. the aminoterminal propeptide of type III
      procollagen, the carboxyterminal propeptide of procollagen I and the bone Gla
      protein, which may turn out to be useful early indicators of the growth response
      to long-term GH therapy.

PMID- 1389088
TI  - Male infertility: current concepts.
AB  - The purpose of the article is to review the current concepts regarding the
      etiology and treatment of male-factor infertility. The following general
      conclusions can be drawn: (a) conventional parameters for sperm quality and male
      fertility are inadequate and any assessment should involve several different
      tests of sperm cell function to increase the fertility prognosis; (b) the causes
      of disturbed sperm quality are still poorly understood; (c) the role of the
      varicocele is still controversial but some of the discrepancies reported in the
      literature may be explained by the negative influence of other factors such as
      smoking, epididymal pathology or glandular infections operating either in
      conjunction or independent of the varicocele; (d) the role of chronic
      inflammatory processes in the reproductive organs, in particular the involvement
      of chronic chlamydial infections, has been underestimated, largely because it is
      often asymptomatic and difficult to demonstrate objectively; (e) partial androgen
      insensitivity may account for a significant number of cases of severe
      oligozoospermia; (f) no major advances have been made in the medical treatment of
      poor sperm quality; (g) assisted fertilization techniques such as IVF and GIFT
      offer encouraging possibilities for the treatment of male-factor infertility; and
      (h) recent advances in microsurgical techniques are increasing the treatment
      possibilities for certain forms of obstructive azoospermia and severe
      oligozoospermia.

PMID- 1389087
TI  - Emerging role of heat shock proteins in biology and medicine.
AB  - All cells, procaryotic and eucaryotic, respond to an elevation in temperature by
      increasing the synthesis of a family of proteins collectively known as heat shock
      proteins (HSPs). HSPs are among the most highly conserved and abundant proteins
      in nature. Studies on the regulation of the synthesis of HSPs have for several
      years shed light on the mechanisms regulating gene expression. The results from
      recent years, showing that HSPs play crucial roles in a wide variety of normal
      cellular processes, has made them an object of even broader interest, first to
      molecular and cellular biologists and later to specialists in various fields of
      medicine including oncology, immunology, infectious disease, autoimmunity,
      embryology, neurology and endocrinology. The aim of this review is to briefly
      summarize our present knowledge of the regulation of the heat shock response and
      the structure of the relevant gene products, HSPs. Moreover, some of the exciting
      associations between HSPs and various fields of medicine will be discussed.

PMID- 1389090
TI  - Eating disorders: antecedents, evolution and course.
AB  - Concepts of eating disorders have altered so that anorexia nervosa is now
      recognized as an important but uncommon syndrome within a spectrum of disordered
      eating. Behaviours used by dieters constitute the mild end of the eating disorder
      spectrum. Dieting in young women is for the most part a transient and benign
      activity without longer-term consequences. However, a group of dieters do
      progress to develop the symptoms and behaviour of eating disorders, so that
      dieting has been associated with an eight-fold rise in the risk of later eating
      disorder. Dieting or factors closely associated may account for most eating
      disorders in young women. Many antecedents of eating disorder appear to operate
      through increasing the risk of dieting rather than determining eating disorders
      specifically. Only the development of further neurotic and depressive symptoms
      characterizes dieters progressing to eating disorders. As the evidence
      implicating dieting in the origin of eating disorders becomes stronger so
      strategies for primary prevention become clearer.

PMID- 1389089
TI  - Transgenic animals as bioproducers of therapeutic proteins.
AB  - Many human therapeutic proteins are currently produced with the aid of
      recombinant DNA technology in microbial bioreactors and a few also in large-scale
      animal cell cultures. Although extremely cost-efficient, the microbial production
      system has many inherent limitations. Micro-organisms, such as bacteria, can read
      the universal genetic code and hence produce human proteins with correct amino
      acid sequence, but cannot carry out post-translational modifications, such as
      glycosylation, or fold the newly synthesized protein properly to ultimately
      generate a biologically active entity. Moreover, even though the production of
      the proteins as such is inexpensive, the downstream processing of the final
      product may be extremely difficult and costly. Many of these disadvantages,
      especially the lack of post-translational modifications, can be overcome by
      employing large-scale animal cell cultures for the production of proteins of
      pharmaceutical interest. However, due to the long generation time and the
      requirement for rich culture media, the use of animal cell bioreactors is
      unacceptably expensive. With the advent of transgenic technology, the production
      of human pharmaceuticals in large transgenic animals has become more and more
      attractive. The use of targeted gene transfer, the expression of the transgene of
      interest can be directed to occur in the mammary gland of large farm animals,
      such as pigs, sheep, goats or dairy cattle, and hence the transgene product is
      ultimately being secreted into the milk. Although not yet in commercial use, the
      last few years have witnessed a remarkable progress in this area and proved the
      feasibility of the use of 'molecular farming' in high-quantity, low-cost
      production of valuable therapeutic or industrial proteins. While reviewing the
      progress of the field over the past few years, we discuss in somewhat greater
      detail aspects connected with the use of dairy cattle as bioproducers of human
      therapeutic proteins.

PMID- 1389092
TI  - Sociocultural aspects of eating disorders.
AB  - Eating disorders, though recognized for centuries, are increasing in prevalence.
      The increase in rate is particularly remarkable over the last 30-40 years. The
      article considers how social function stems from biological function and
      evolution, and how biological function may hamper social development to the
      detriment of individuals. Social and cultural influences relevant to this change
      are examined, especially the changing position of women within society as a whole
      and the multiplication of conflicting roles which women find themselves
      balancing. Reference is made to the representation of women in the arts and
      media. Reference is also made to the role of those external agencies which have
      historically controlled populations (both men and women), such as religious
      bodies and governments, but which to some extent have been rejected. Evidence
      from in-depth studies of women with eating disorders and from transcultural
      studies are included to support the authors' ideas.

PMID- 1389091
TI  - Reproductive functions in eating disorders.
AB  - This article reviews current knowledge about the effects of anorexia nervosa,
      bulimia nervosa and partial syndromes on ovulation, menstruation, sexuality,
      fertility, pregnancy and fetal-infant health. Eating disorders may result in
      failure to ovulate, oligomenorrhea, amenorrhea, reduced sex drive, infertility,
      hyperemesis gravidarum, low maternal weight gain in pregnancy, small babies for
      gestational date, low birth weight infants, increased neonatal morbidity and
      problems in infant feeding. The available information suggests that clinicians
      should inquire about nutritional intake, a history of eating disorders and weight
      reducing behaviours as part of the routine assessment of patients with the
      disorders of reproductive function listed above. If an eating disorder is
      discovered before conception, the woman should be encouraged to delay pregnancy
      until the eating disorder is treated and effectively under control. If the woman
      is pregnant, early diagnosis and treatment are essential to reduce maternal and
      fetal complications. The infants of eating-disordered women should be carefully
      followed to ensure adequate nutritional intake. Problems in reproductive function
      related to eating disorders offer rich opportunities for multispecialty
      collaboration in primary and secondary prevention programmes directed toward both
      mother and infant.

PMID- 1389093
TI  - The treatment of bulimia nervosa.
AB  - Bulimia nervosa is a significant source of morbidity amongst young women. There
      has been a considerable body of work on its treatment since it was first
      described in 1979. Three treatments have shown particular promise: antidepressant
      drug treatment, cognitive behaviour therapy and exposure with response
      prevention. The research findings indicate that the approach of choice is
      cognitive behaviour therapy, with most patients benefiting significantly and the
      changes being well maintained. However, cognitive behaviour therapy is neither
      necessary nor sufficient for all patients with bulimia nervosa: some benefit from
      simpler interventions whilst others fail to respond. At present, too little is
      known about the factors that predict response to particular forms of treatment to
      allow the matching of patients with treatments.

PMID- 1389094
TI  - Binge eating in the obese.
AB  - This review will first describe problems in the definition of the term binge
      eating, especially in the absence of purging (vomiting, laxative abuse). We
      highlight current approaches in the classification of obesity, and then provide
      an overview of the available literature on differences between obese binge eaters
      and obese non-binge eaters. Many studies indicate that binge eating is common
      among the female obese, with a frequency ranging from 23 to 46% among those
      seeking treatment for weight reduction. Despite differences in the definitions of
      binge eating and variability among the samples investigated, there is strong
      evidence that binge eaters represent a distinct subgroup among the obese. Binge
      eating obese exhibit significantly more eating and weight-related pathology, as
      well as more psychopathology compared to their non-binge eating obese
      counterparts.

PMID- 1389095
TI  - NCLAN results and their application to the standard-setting process: protecting
      vegetation from surface ozone exposures. National Crop Loss Assessment Network.
AB  - The current form of the standard is not appropriate for protecting vegetation
      from O3 exposures. As an alternative to the current form of the standard, it has
      been suggested in the literature that a maximum cumulative 3-month SUM06 O3
      exposure index be used as the form of a secondary standard to protect
      agricultural crops. However, applying this index may result in inconsistent
      protection for vegetation. It appears that cumulative indices will have to be
      combined with other parameters to accurately quantify the occurrence of high
      hourly average concentrations. This paper describes the characterization of the
      hourly O3 exposures in selected National Crop Loss Assessment Network (NCLAN)
      experiments and discusses the application of the results to the standard-setting
      process. Our results indicated that, in most cases, the NCLAN experimental data
      we analyzed appeared to support the observation that the repeated occurrences of
      hourly average O3 concentrations of 0.10 ppm and higher result in adverse effects
      on vegetation. For the NCLAN experiments, the characterized distributions
      reflected the ability of the high hourly average concentrations to affect crop
      yield reduction. Prior to suggesting a new form of the secondary standard, it
      will be important to carefully characterize the specific regimes responsible for
      affecting vegetation and identify the important components of those regimes
      responsible for the effects. By applying this approach, it should be possible to
      limit the occurrence of inconsistent results when applying a new form of the
      secondary standard.

PMID- 1389096
TI  - Beta-cell expression of 65-kDa heat-shock protein mRNA is function- and age
      dependent.
AB  - This study examined the expression of mRNA coding for the 65-kDa heat-shock
      protein (HSP) in rat islet cells of different functional states and different
      ages. In addition, beta cells and non-beta cells purified by fluorescence
      activated cell sorting were studied. Total RNA from islet cells and insulin
      producing RINm5F cells was isolated and analyzed by Northern blotting using a
      cDNA probe coding for the human homologue to the mycobacterial 65-kDa HSP, after
      which blots were quantified by densitometric scanning. Isolated beta cells were
      found to express 65-kDa HSP mRNA. The expression was increased in Lewis islet
      cells exposed to heat shock or high glucose concentration, four- and three-fold,
      respectively (p < 0.01). In isolated beta cells cultured at high glucose
      concentration a doubling in the content of 65-kDa HSP mRNA was seen compared with
      islets cultured at low glucose concentration (p < 0.05). In islets from Lewis
      rats fasted for 24 h, the content of 65-kDa HSP mRNA was 42% lower than in islets
      isolated from normally fed Lewis rats (p < 0.01). Both in BB rats and Wistar
      Furth rats the content of 65-kDa HSP mRNA was found to be higher in the 30- and
      the 60-day-old rats compared with the neonatal animals (p < 0.01). The expression
      of 65-kDa HSP mRNA was increased in RINm5F cells following heat shock, while no
      induction was seen after stimulation with glucose, TPA or IBMX. It is concluded
      that the 65-kDa heat-shock protein belongs to the family of inducible functional
      antigens in beta cells, which strengthens the interest in 65-kDa HSP as an
      antigen possibly involved in the initiation of autoimmune beta-cell destruction.

PMID- 1389097
TI  - Growth patterns of pulmonary metastases and primary tumours from five murine
      fibrosarcoma cell clones.
AB  - The growth patterns, including the size, shape and regional preferences, of lung
      metastases from five murine fibrosarcoma cell clones were studied. Spontaneous
      metastases developed from tumours formed by subcutaneous inoculation of the cell
      clones. Lung colonies (experimental metastases) were established by i.v.
      injection of cells. The numbers of both spontaneously and experimentally formed
      subpleural lung metastases were counted through a stereomicroscope. The fraction
      of colonies that was located subpleurally was determined in histological sections
      of lungs. The growth kinetics of clonally derived primary tumours, and the number
      of spontaneous and experimental lung metastases, differed greatly between certain
      cell clones. The number of spontaneous lung metastases was correlated with the
      maximum size of primary tumours. No close correlation was observed between the
      size of the primary tumours and the size of experimental metastases. There were
      differences between the cell clones in the shape and regional preferences of
      their lung deposits. The subpleural colonies were generally larger than the
      intrapulmonary ones. Thus, both the regional distribution and the growth pattern
      of lung deposits differed between the clones.

PMID- 1389098
TI  - Prevalence of antibodies against heat-stable antigens from Helicobacter pylori in
      patients with dyspeptic symptoms and normal persons.
AB  - Heat-stable antigens from Helicobacter pylori were investigated for the detection
      of serum IgG, IgA and IgM antibodies against H. pylori by an ELISA technique.
      Antibody titers against H. pylori were measured in 167 dyspeptic patients, of
      whom 96 were H. pylori positive confirmed by culture or microscopy, and in 482
      controls (0-98 years). Increased IgG antibody titers were found significantly
      more often in dyspeptic patients with active chronic gastritis than in patients
      with normal morphology, as well as in H. pylori-positive patients as compared to
      H. pylori-negative patients, independent of the endoscopic findings. The heat
      stable antigens were compared with acid glycine-extracted antigens and a high
      degree of concordance was found in the results obtained with the two antigen
      preparations. The differences in the IgA antibody titers against H. pylori
      between H. pylori-positive and H. pylori-negative dyspeptic patients were
      significant and may be useful to confirm a borderline IgG result. No differences
      were found in IgM antibody titer between H. pylori-positive and -negative
      patients. The greatest age-dependent increase in IgG and IgA antibody titers was
      found in children, and if a lower cut-off level is used for children than for
      adults, as has been proposed, the proportion of people with increased antibody
      titers against H. pylori would be almost constant from the age of between five
      and 10 years until the time between 61 and 80 years. Comparison of H. pylori IgG
      antibodies with IgG antibodies against Campylobacter jejuni and total antibodies
      against cytomegalovirus (CMV) showed a greater similarity between H. pylori and
      C. jejuni (R = 0.51) than between H. pylori and CMV (R = 0.22). This may possibly
      be caused by cross-reactions between H. pylori and C. jejuni. The H. pylori heat
      stabile antigen seems not to be very different from other crude H. pylori
      antigens like acid glycine-extracted antigens, but purification and
      characterization of the antigens are needed to improve antibody assays.

PMID- 1389099
TI  - Expression of epidermal growth factor receptor in human meningiomas and meningeal
      tissue.
AB  - The aim of this study was to examine meningeal tissue under normal, reactive, and
      neoplastic conditions for expression of epidermal growth factor receptor (EGFR)
      using an improved histochemical method, namely biotinylated epidermal growth
      factor. EGFR was found in all the examined meningiomas (12 benign and three
      anaplastic) and in neonatal rat meninges, whereas normal and injured adult human
      and rat meninges did not exhibit detectable EGFR. These observations indicate
      that EGFR is involved in the development of meningeal tissue. Further, EGFR is
      abnormally expressed in meningeal tumours, indicating a role of EGFR in the
      neoplastic process of these tumours. The regular expression of EGFR in human
      meningiomas suggests EGFR as a tumour marker for this tumour type.

PMID- 1389100
TI  - Cancer-associated changes in glycosylation of fibronectin. Immunohistological
      localization of oncofetal fibronectin defined by monoclonal antibodies.
AB  - The extracellular matrix adhesion molecule fibronectin exhibits different
      isoforms derived by alternative splicing as well as recently demonstrated
      variation in O-glycosylation. Although fibronectin is widely distributed in
      normal tissues, the individual isoforms have been found to show restricted tissue
      distribution and association with malignancies. The monoclonal antibody FDC-6
      defines a cancer-associated de novo glycosylation of a specific threonine residue
      in the C-terminal region of the fibronectin molecule termed oncofetal
      fibronectin. Here we report an immunohistological study of oral squamous cell
      carcinomas (n = 33), premalignant lesions (n = 15), and normal oral mucosa (n =
      10) using the FDC-6 antibody. A selective expression of the oncofetal fibronectin
      epitope was demonstrated in close relation to the invading carcinoma, whereas no
      staining was observed in premalignant lesions without epithelial dysplasia, or in
      normal epithelium. Furthermore, we attempted to identify additional carbohydrate
      related epitopes distinguishing fibronectin of human hepatoma cell line HUH-7
      from plasma fibronectin. No novel epitopes were identified, as all generated
      monoclonal antibodies lacking reactivity with plasma fibronectin showed the same
      specificity as FDC-6. Previous studies have indicated that the de novo
      glycosylation is induced by a novel transferase activity only found in fetal and
      carcinoma cell lines, placenta and hepatoma tissues. Here we provide further
      evidence that a purified UDP-GalNAc:peptide N-acetylgalactosaminyltransferase
      from normal bovine thymus and human placentae is incapable of utilizing the
      hexapeptide VTHPGY as a substrate. The results demonstrate that oncofetal
      fibronectin is highly associated with malignancy, and appears to be induced by
      expression of a unique glycosyltransferase or modification of the specificity of
      the normally expressed transferase.

PMID- 1389101
TI  - Vegetable oils instead of xylene in tissue processing.
AB  - In an effort to improve working conditions in the histopathologic laboratory, we
      have investigated whether less toxic substances may be substituted for the toxic
      organic solvent xylene currently in use. Xylene is used in the clearing as well
      as the deparaffinization process. We have tested whether the substitution of
      xylene by olive oil and coconut oil leads to any difference in the quality of the
      histologic sections. Two tissue blocks from each of 232 specimens sent for
      histopathologic evaluation were subjected to parallel processing in xylene and
      oil. The specimens represented a broad spectrum of tissue types. All sections
      were stained with hematoxylin-eosin to permit evaluation of histologic and
      cytologic details. Furthermore, a range of histochemical and immunohistochemical
      stainings were applied to a subgroup of tissue sections. The results showed
      qualitative differences between xylene-processed and oil-processed tissue in only
      a minority of cases. In no cases were the oil-processed samples considered less
      suitable for histologic diagnosis. In the histochemical and immunohistochemical
      stainings, no differences were registered. Although the long-term stability of
      oil-processed tissue remains to be clarified, we conclude that less toxic
      vegetable oil may probably be substituted for xylene without losing valuable
      diagnostic information.

PMID- 1389102
TI  - Histological examination of the rabbit middle ear in secretory otitis media with
      and without a ventilation tube.
AB  - To study the time-related histopathological lesions in secretory otitis media as
      it develops into the chronic stage, including the influence of ventilation of the
      middle ear, we examined the middle ear mucosa in a rabbit model. The observation
      period was from two weeks until 18 months. The histological method applied
      included haematoxylin-eosin and Sirius red staining for morphometric
      quantification of the goblet cells, the thickness of the connective tissue layer,
      the area fractions of blood vessels, inflammatory cells, fibroblasts and collagen
      fibres. In conclusion, the middle ear mucosa in secretory otitis media exhibited
      inflammatory changes correlating with the duration of the disease. Ventilation of
      the middle ear in secretory otitis media did not improve the changes.

PMID- 1389103
TI  - Estimation of the total number of mast cells in the human umbilical cord. A
      methodological study.
AB  - The aim of the present study was to estimate the total number of mast cells in
      the human umbilical cord. Using 50 microns-thick paraffin sections, made from a
      systematic random sample of umbilical cord, the total number of mast cells per
      cord was estimated using a combination of the optical disector and fractionated
      sampling. The mast cell of the human umbilical cord was found in Wharton's jelly,
      most frequently in close proximity to the three blood vessels. No consistent
      pattern of variation in mast cell numbers from the fetal end of the umbilical
      cord towards the placenta was seen. The total number of mast cells found in the
      umbilical cord was 5,200,000 (median), range 2,800,000-16,800,000 (n = 7), that
      is 156,000 mast cells per gram umbilical cord (median), range 48,000-267,000.
      Thus, the umbilical cord constitutes an adequate source of mast cells for further
      investigation of these cells in the newborn, e.g. for describing their functional
      and secretory characteristics and possible clinical relevance in relation to the
      development of allergic, inflammatory and immunological diseases in infancy and
      childhood.

PMID- 1389104
TI  - Killing curve activity of ciprofloxacin is comparable to synergistic effect of
      beta-lactam-tobramycin combinations against Haemophilus species endocarditis
      strains.
AB  - Nine Haemophilus species strains, all beta-lactamase negative, isolated from
      patients with endocarditis were tested in killing curve experiments. Antibiotics
      used were penicillin, amoxicillin, aztreonam alone and in combination with
      tobramycin, as well as ciprofloxacin alone. Synergism between beta-lactams and
      tobramycin with reduction of colony counts to zero was seen after 24 h for H.
      influenzae, H. parainfluenzae and H. segnis strains. Ciprofloxacin was as
      effective as beta-lactam-tobramycin combinations. The H. aphrophilus strain was
      not killed as effectively as other strains by any of the antibiotics.

PMID- 1389105
TI  - Quantitative estimation of diphtheria and tetanus toxoids. 6. Use of different
      antibody titration methods for evaluation of immunogenicity in animals during
      potency assay of diphtheria toxoid.
AB  - Two diphtheria toxoid preparations were compared in potency assays in guinea-pigs
      using different methods for evaluation of the responses to vaccination. The
      methods used were the direct skin challenge (Schick test) and ELISA and VERO cell
      titration of antibodies. The different evaluation methods resulted in the same
      relative potencies between the toxoids. It was observed that when first
      vaccination sera were compared with a second-vaccination serum, the relative
      antibody concentration depended on whether ELISA or VERO cell titration was used.

PMID- 1389106
TI  - Detoxification of diphtheria and tetanus toxin with formaldehyde. Detection of
      protein conjugates.
AB  - In a model system of purified diphtheria and tetanus toxins it was shown that
      conjugates between the two proteins are formed during detoxification with
      formaldehyde. Detoxification mixtures were fractionated by HPLC. Two protein
      conjugates with different molecular weights were detected and quantified by
      capture ELISA assay. In vivo the existence of the largest diphtheria-tetanus
      toxoid conjugate was demonstrated by its antibody response in mice vaccinated
      with a calcium phosphate adjuvated column fraction of detoxification mixture. To
      eliminate the risk of cross-linking foreign proteins to toxoids in an attempt to
      reduce the frequency of adverse reactions in vaccination programmes, it is
      preferable to purify toxins before treatment with formaldehyde.

PMID- 1389107
TI  - Variation in the biological function of envelope protein epitopes of yellow fever
      vaccine viruses detected with monoclonal antibodies.
AB  - Three different virus strains (17D-204, 17DD and the French neurotropic vaccine)
      have been used as live attenuated yellow fever (YF) vaccines and are manufactured
      in different centres around the world. The envelope proteins of these vaccine
      viruses were examined and compared using mouse monoclonal antibodies (MAbs) in
      haemagglutination inhibition (HAI) and neutralization (N) tests. The epitopes
      eliciting HAI and/or N were found to vary depending on the virus examined. Such
      variation was also found between vaccine viruses of the same strain manufactured
      in different centres. These data were confirmed by the use of mouse polyclonal
      antisera. On the basis of the MAb results in HAI tests a dendrogram of the
      similarity coefficients between the viruses was constructed and showed that the
      viruses could be placed into three major groups. Thus, it is concluded that YF
      vaccines manufactured in different centres are antigenically distinct as
      recognized by the mouse immune system.

PMID- 1389108
TI  - Potency assays for Anistreplase: comparison of the fibrin plate assay and a 96
      well plate assay.
AB  - Several production lots of Anistreplase (Eminase) were assayed for potency by
      either two fibrin plate assays or a clot lysis assay performed in 96-well
      microtiter plates. The 96-well plate assay yielded comparable data to the fibrin
      plate assays and had the advantage of greater efficiency with respect to both
      time and reagents. As a result the newer method appears to be a suitable
      alternative to the fibrin plate assays for lot release of Anistreplase.

PMID- 1389109
TI  - Application of the euglycaemic clamp technique to bioassay of insulin analogues.
AB  - The euglycaemic clamp method may offer a precise and clinically valid approach to
      assess the in vivo potency of new insulin analogues or derivatives relative to a
      human insulin standard. The proposed protocol was designed to overcome problems
      due to differences in pharmacokinetics between the test and standard
      preparations. An analogue of human insulin, GlyA21+ArgB27+ThrB30-NH2, which is
      absorbed very slowly after subcutaneous injection, and human insulin were
      compared in intravenous clamp experiments in pigs. Both insulins were infused for
      4 h to achieve steady state glucose metabolism. The infusion rate ranged from 2.5
      8 pmol min-1 kg-1. Parallel dose response curves were obtained with the mean
      glucose infusion rate from 180-240 min as the response and the logarithm of the
      insulin infusion rate as the dose. Standard bioassay analysis showed that the
      molar potency of the analogue relative to human insulin was 95.2% with a 95%
      confidence interval of 82.3-111.2%. To assess the clinical validity of the method
      a similar euglycaemic clamp study was carried out in human volunteers. The
      insulin infusion rates were 3 and 6 pmol min-1 kg-1, and the mean glucose
      infusion rate over the final 180-240 min period of the clamp was used as
      response. The statistical analysis showed, as in the pig clamp bioassay, no
      significant deviations from steady state or from the assumption of parallelism.
      The resulting molar potency of the analogue relative to human insulin was 85.5%
      with a 95% confidence interval of 49.5-128.4%. This was in agreement with the
      result of the pig clamp bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389110
TI  - Report of a collaborative study to assess the determination of glycoprotein
      antigen content of rabies vaccines for human use.

PMID- 1389111
TI  - Note for guidance. Guidelines for minimizing the risk of transmitting agents
      causing spongiform encephalopathy via medicinal products. Committee for
      Proprietary Medicinal Products: Ad Hoc Working Party on Biotechnology/Pharmacy
      and Working Party on Safety Medicines.

PMID- 1389113
TI  - Views on the issues raised in recent letters by Galibert recommending studies for
      genetic stability testing of cells used to manufacture purified polypeptide
      pharmaceutical products utilizing recombinant DNA (rDNA) technology. Committee on
      Process Development and Manufacturing.

PMID- 1389112
TI  - Note for guidance. Guidelines for medicinal products derived from human blood and
      plasma. Committee for Proprietary Medicinal Products: Ad Hoc Working Party on
      Biotechnology/Pharmacy and Working Party on Safety Medicines.

PMID- 1389114
TI  - Safety aspects in the manufacturing of plasma-derived coagulation factor
      concentrates.
AB  - Plasma-derived coagulation factor concentrates, prepared using traditional
      manufacturing processes, have transmitted viral diseases, especially AIDS,
      hepatitis B and hepatitis C to patients. To date, more extensive selection of
      blood donors, improved screening procedures of each plasma donation for direct
      and indirect viral markers, and newly developed virucidal procedures, especially
      pasteurization and solvent-detergent, together with extraction technologies of
      plasma proteins based on high-resolution chromatographic separations, have
      diminished considerably the risks of transmitting these pathogenic agents. To
      ensure safety, each production process must be carefully validated, following a
      rigorous scientific approach to assess its ability to inactivate or eliminate
      viruses. In addition, Good Manufacturing Practices must avoid any variation from
      these validated viral inactivation processes and must eliminate risks of
      potential downstream contamination of purified plasma fractions following viral
      inactivation or elimination steps. Other side-effects associated with
      conventional low-purity preparations, such as acute haemolytic anemia due to
      contamination by isohaemagglutinins, or immunosuppression possibly due to an
      overload in fibrinogen and immunoglobulins, have not been reported following
      infusion of highly purified coagulation factor concentrates. Present state-of-the
      art virus inactivation and protein-purification technologies have significantly
      improved the safety of plasma coagulation factor concentrates.

PMID- 1389115
TI  - The construct of brain maturation in theories of child development.
AB  - Developmental psychologists have avoided using brain maturation as a primary
      construct in theories of child development for a variety of reasons during the
      past 40 years. However, during the last decade we have seen a return to
      considering brain growth as a useful element in theory construction. During the
      past few years, the frontal lobe has received increasing attention with respect
      to major developmental issues. In this Introduction, we review some of these
      historical and contemporary trends.

PMID- 1389116
TI  - Attention deficit hyperactivity disorder and the frontal lobe syndrome.
AB  - The usefulness of frontal lobe (FL) dysfunction as a conceptual model for
      Attention Deficit Hyperactivity Disorder (ADHD) was investigated. Twenty-four
      ADHD and 24 normal control (NC) children were tested using two batteries of
      tasks. The first was sensitive to FL deficits in motor control and problem
      solving skills. The second consisted of memory tasks sensitive to temporal lobe
      dysfunction. ADHD children differed significantly from NCs on measures of FL
      function, but not on tests of temporal lobe functions. Where norms were available
      for normal children on the same FL tests, ADHDs performed like 6- to 7-year-olds,
      despite their mean age of 10 years and minimum age of 8 years. The differential
      performance of ADHDs on tasks sensitive to FL and temporal lobe dysfunction
      supports the hypothesis that ADHD deficits are analogous to FL dysfunction and
      demonstrates that the children's deficits do not reflect generalized cognitive
      impairment.

PMID- 1389117
TI  - Anterior cerebral asymmetry and the nature of emotion.
AB  - This article presents an overview of the author's recent electrophysiological
      studies of anterior cerebral asymmetries related to emotion and affective style.
      A theoretical account is provided of the role of the two hemispheres in emotional
      processing. This account assigns a major role in approach- and withdrawal-related
      behavior to the left and right frontal and anterior temporal regions of two
      hemispheres, respectively. Individual differences in approach- and withdrawal
      related emotional reactivity and temperament are associated with stable
      differences in baseline measures of activation asymmetry in these anterior
      regions. Phasic state changes in emotion result in shifts in anterior activation
      asymmetry which are superimposed upon these stable baseline differences. Future
      directions for research in this area are discussed.

PMID- 1389118
TI  - The role of frontal lobe functioning in the development of infant self-regulatory
      behavior.
AB  - In the last two decades, there has been tremendous growth in two fields of study
      related to human infant development: (1) the development of neural processes
      during the early postnatal years and (2) the development of self-regulatory
      behavior. In an attempt to stimulate research on the relation between early brain
      development and self-regulatory processes, several hypotheses pertaining to the
      role of frontal lobe functioning in the development of emotion regulation during
      infancy are proposed. The results of a study of the relation between frontal
      electroencephalographic (EEG) activity and emotional behavior of 21-month-old
      infants are reported. It was found that increases in frontal lobe activation were
      associated with increases in emotional arousal, while EEG activity recorded from
      the parietal region showed either a reciprocal pattern of activation or did not
      change as a function of level of emotional arousal. These results provide
      evidence for the specialized role of the frontal lobe in mediating emotional
      behavior during infancy.

PMID- 1389119
TI  - Electrophysiological studies of emotional processes: a developmental-clinical
      perspective.

PMID- 1389120
TI  - The impact of a right prefrontal lesion on the developing brain.

PMID- 1389121
TI  - Cyclic cortical reorganization during early childhood.
AB  - EEG coherence was computed from 8 left and 8 right intrahemispheric electrode
      pairs from 253 children ranging in mean age from 6 months to 7 years. The first
      derivative of mean coherence was computed in order to study growth spurts or
      rapid changes in mean coherence over the early childhood period. Growth spurts in
      EEG coherence were approximately 6 months to 1 year in duration and involved a
      cyclical process composed of a sequential lengthening of intracortical
      connections in the left hemisphere and a sequential contraction of intracortical
      connections in the right hemisphere. Each growth spurt cycle had a period of
      approximately 2 to 4 years and involved both a rostral-caudal expansion and
      contraction as well as a lateral-to-medial rotation. Data support the view that
      the functions of the left and right hemisphere are established early in human
      development through complementary developmental sequences and that these
      sequences appear to recapitulate differences in adult hemispheric function.

PMID- 1389123
TI  - Developmental changes in the recognition and comprehension of facial expression:
      implications for frontal lobe function.
AB  - Children aged 6-15 years old and adults (over 18) were given three tests designed
      to test perception and comprehension of facial expression. In the first test
      subjects were given two composite symmetrical faces made from the left or right
      half of a normal face, the subjects' task being to indicate which composite more
      closely resembled the original face. In the second test the subjects matched a
      series of photographs from Life magazine with key photographs of one of six
      distinct emotions (sad, fear, happy, anger, disgust, surprise). In the third test
      the subjects chose a key photograph that was appropriate for the face of a
      faceless character in a cartoon. On the composite faces test the subjects in all
      groups exhibited a preference for the left visual field composite, implying that
      all age groups were processing the faces in a similar manner. The results of the
      other two tests showed that there was an improvement in the perception of facial
      expression between the ages of 6 and 8 years, little change until about 13 years,
      and then a second improvement to adult performance at about 14 years. The
      performance of the 8- to 13-year-old children was similar to that of adult
      patients with frontal lobe injuries, which could be taken as evidence that the
      regions of the frontal lobe involved in the performance of these tasks may not be
      mature until about 14 years of age.

PMID- 1389122
TI  - The role of the frontal lobes in the regulation of cognitive development.
AB  - Between the ages of 1.5 and 5 years, and again between the ages of 5 and 10
      years, a sequence of changes takes place in children's behavior which indicates a
      fundamental reorganization of their attentional, executive, and self-reflexive
      processes. In the present article, these changes are summarized, and evidence is
      adduced to support the claims (1) that these changes are frontally mediated and
      (2) that the underlying mechanism that generates them is similar to the one that
      generates the changes in EEG coherence during the same time period. The
      psychological model that has been hypothesized to explain the cycles of cognitive
      development (Case, 1992) is then compared to the physiological model that has
      been proposed to explain cycles of EEG development (Thatcher, 1992). It is shown
      that the two models are complementary, both in the underlying developmental
      sequence that they postulate and in the recursive dynamic they propose for
      producing movement through this sequence. A number of implications and
      predictions are derived, which follow from the proposition that the two sets of
      changes are different manifestations of a common underlying process.

PMID- 1389124
TI  - Biological and psychological development of executive functions.
AB  - The purpose of this overview is to provide a background for understanding the
      relation between the biological maturation of the frontal lobes and the
      development of the psychological concept of executive functions. In the first
      section, an interactive hierarchical feedback model is presented as a heuristic
      way of conceptualizing the relationship of the frontal lobes and executive
      functions to other brain regions and abilities. The following two sections
      present a synopsis of research on biological maturation and the psychological
      development of executive functions.

PMID- 1389126
TI  - Management of congenital dacryocystocoele.
AB  - Congenital dacryocystocoele occurs when the nasolacrimal drainage apparatus in
      the newborn has concomitant blocks at the level of the junction of the common
      canaliculus with the lacrimal sac and at the distal end of the nasolacrimal duct.
      This results in a typical pink or blue swelling in the region of the medial
      canthus. Spontaneous resolution is common, although dacryocystitis may supervene.
      Treatment should be conservative unless dacryocystitis occurs, or intranasal
      extension coexists. A series of seven consecutive cases is presented and a
      management plan for the neonate with congenital dacryocystocoele is proposed.

PMID- 1389125
TI  - Lateral versus frontal ERP predictors of reading skill.
AB  - Neuropsychological factors that could account for good versus poor reading skills
      include hemispheric asymmetry for language, signal processing efficiency,
      hemisphericity, and frontally based control of attention. Using event-related
      potential (ERP) measures of these constructs, we find that only hemisphericity
      accounts for individual differences in reading skill among our 15-year-old good
      readers, while the frontally generated Contingent Negative Variation attentional
      ERP accounts for reading skill differences among the poor readers. While good
      readers show expected hemispheric ERP asymmetries and poor readers do not, this
      group difference does not account for the variation in reading skill. These data
      suggest that below some crucial threshold, reading disability is predicted by
      frontal attentional skill, whereas above this threshold, good reading is better
      predicted by hemisphericity.

PMID- 1389127
TI  - The surgical management of congenital lacrimal fistulae.
AB  - Congenital lacrimal fistulae are developmental anomalies of the lacrimal
      apparatus that are usually symptomatic, frequently causing epiphora and
      occasionally causing fistulitis or dacryocystitis. They may be associated with
      other abnormalities of the lacrimal system or with systemic anomalies. Complete
      excision alone, or in combination with nasolacrimal intubation and/or
      dacryocystorhinostomy is recommended for treatment.

PMID- 1389128
TI  - A clinicopathological study of loop recession in strabismus.
AB  - This communication reports the histological structure of loop recessions of
      extraocular muscles from seven patients. In all cases the loops formed
      pseudotendons in which the typical histological structure was well established by
      four months. Subsequently, moulding of these pseudotendons occurred with improved
      alignment of collagen and decrease in vascularity. By three and a half years
      after the operation the pseudotendon had acquired a very close resemblance to
      true tendon.

PMID- 1389129
TI  - The role of botulinum toxin in third nerve palsy.
AB  - Isolated third nerve paresis is a rare diagnosis among patients presenting to the
      Botulinum Toxin Clinic at Moorfields Eye Hospital. Ten patients with this
      diagnosis are reviewed in this study. Head trauma is a common cause of third
      nerve palsy and is often severe enough to cause damage to fusion potential. If
      fusion is present and there is adequate adduction of the divergent eye, then
      botulinum toxin injection of the lateral rectus may induce long-term control of
      the ocular deviation. Three of the four patients who experienced long-term
      control of their ocular deviation following toxin injection shared these
      features. Toxin injected into the lateral rectus did not, however, reliably
      assess medial rectus function and therefore predict the outcome of horizontal
      squint surgery. Reasons for this are discussed.

PMID- 1389130
TI  - Pterygium treatment with triethylene thiophosphoramide.
AB  - In this study 146 pterygia were excised from 116 patients. The eyes were treated
      with Thiotepa eyedrops over four weeks to discourage regrowth. All treatment was
      carried out by the one surgeon on consecutive patients. The relationship between
      pinguecula and pterygium is explored, and the pathogenesis of pterygium growth
      discussed.

PMID- 1389131
TI  - Successful outcome following anastomosis of a severed trochlear nerve in the
      middle fossa.
AB  - Complete return of function has been obtained following neurosurgical repair of a
      trochlear nerve inadvertently divided during the clipping of a basilar tip
      aneurysm. To date this is the second case reported in the literature. The
      technique of repair and the method of recording the return of function is
      discussed.

PMID- 1389132
TI  - Third nerve palsy due to cerebral artery aneurysm in a child.
AB  - We report a case of cerebral aneurysm in a seven-year-old girl who presented with
      subacutely progressive third nerve palsy. To our knowledge this is the youngest
      reported patient with this condition. Confusion with myasthenia gravis occurred
      because of improvement in the patient's ptosis after intravenous edrophonium
      chloride. Cerebral CT revealed a hyperdense mass that was characterised on
      cerebral angiography as an aneurysm of the posterior communicating artery.
      Another occult aneurysm of the posterior cerebral artery was found at surgery.
      This case demonstrates that third nerve palsy due to cerebral aneurysm may affect
      patients at a younger age than has previously been recognised. Therefore we
      suggest that even young children should have aneurysm excluded by cerebral CT and
      angiography if they present with acquired third nerve palsy involving the pupil.
      In addition this case highlights the false-positive results that may occur with
      the edrophonium chloride test for myasthenia gravis.

PMID- 1389133
TI  - Spontaneous detachment of iris pigment epithelium.

PMID- 1389134
TI  - Inexpensive punctal plugs for dry eyes.

PMID- 1389135
TI  - The 'Cuban treatment' for retinitis pigmentosa.

PMID- 1389136
TI  - Single-injection peribulbar local anaesthesia.

PMID- 1389137
TI  - In defence of phaco.

PMID- 1389138
TI  - In defence of phaco.

PMID- 1389139
TI  - In defense of phaco.

PMID- 1389140
TI  - Present challenges in the global prevention of blindness.
AB  - Cataract is responsible for 50% of world blindness, with at present an estimated
      backlog of 13.5 million cases in need of surgery. Low-cost cataract surgery must
      be made more available in developing countries, making use of alternative
      approaches for outpatient surgery and optimal management of available resources.
      Trachoma control needs to be targeted at the worst affected areas in endemic
      countries, with more emphasis on behavioural, educational and community aspects
      of the disease. Vitamin A deficiency and xerophthalmia control are becoming
      matters of maternal and child health care, with early intervention during infancy
      in view of the mortality issue. There are good prospects for the prevention of
      blindness from onchocerciasis, through the availability of ivermectin, but large
      scale distribution schemes are still needed in most of the African countries
      concerned. The early detection and management of open-angle glaucoma still poses
      a major problem in developing countries, and further development of appropriate
      technology is needed in this field. Another area where more efforts are needed is
      ocular trauma, which is commonly the cause of unilateral loss of vision. General
      preventive measures must be enforced and better training provided to health
      personnel to deal competently with such cases, in order to prevent late
      complications. Diabetes, finally, is on the increase in many developing
      countries, giving rise to problems in dealing effectively with the ensuing
      retinopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389141
TI  - Epidemiological patterns of ocular trauma.
AB  - Ocular trauma is the cause of blindness in approximately half a million people
      worldwide, and many more have suffered partial loss of sight. Trauma is often the
      most important cause of unilateral loss of vision, particularly in developing
      countries. There is a cumulative risk of ocular trauma and visual loss during
      life, but the true incidence of accidents involving the eyes is not known. Males
      tend to have more eye trauma than females, and this is already apparent from
      childhood; lower socioeconomic classes are also more associated with ocular
      trauma. The setting for the occurrence of trauma is most commonly the workplace
      and, increasingly, road accidents. On the other hand, domestic accidents are
      probably under-reported. Of particular importance in some developing countries is
      the occurrence of superficial corneal trauma in agricultural work, often leading
      to rapidly progressing corneal ulceration and visual loss. The impact of ocular
      trauma, in terms of need for medical care, loss of income and cost of
      rehabilitation services when indicated, clearly makes the strengthening of
      preventive measures very worthwhile.

PMID- 1389142
TI  - Submandibular gland transfer in the correction of dry eye.
AB  - Following rabbit experiments which showed that microvascular submandibular gland
      transfer could ameliorate the deleterious effects of lacrimal gland ablation, a
      clinical transfer of the submandibular salivary gland to the temple region was
      performed. The beneficial results from this initial operation have led to the
      procedure being used in a total of eight patients with 12 transfers. The
      procedure has led to increased moisture in the eye and decreased symptoms but the
      assessment of change in corneal function and pathology is difficult.

PMID- 1389143
TI  - A rapid and efficient protocol of the inverted PCR using two primer pairs.

PMID- 1389144
TI  - Utilizing uracil DNA glycosylase to control carryover contamination in PCR:
      characterization of residual UDG activity following thermal cycling.

PMID- 1389145
TI  - An improved method for rapid screening of baculovirus recombinant plaques by PCR
      amplification.

PMID- 1389146
TI  - The efficiency of restriction endonuclease digests determined by PCR.

PMID- 1389147
TI  - Identification of point mutations at codon 61 of the c-Ha-ras gene by single
      strand conformation polymorphism analysis.

PMID- 1389148
TI  - Improved sequencing of "mini-prep" double-stranded templates using a multiwell
      microplate system.

PMID- 1389149
TI  - Facile isolation of genomic DNA from filamentous fungi.

PMID- 1389150
TI  - Silicone spray as an aid for drying DNA sequencing gels.

PMID- 1389151
TI  - Recovery of DNA from agarose gels stained with methylene blue.

PMID- 1389152
TI  - A rapid, inexpensive method for eluting DNA from agarose or acrylamide gel slices
      without using toxic or chaotropic materials.

PMID- 1389153
TI  - UV absorption complicates PCR decontamination.
AB  - UV irradiation is widely used to inactivate contaminating DNA in PCR. Highly UV
      absorbent deoxyribonucleoside triphosphates in PCR mixtures reduce the efficiency
      of UV decontamination. Optimal decontamination may be achieved by irradiating the
      PCR mixture without the deoxyribonucleoside triphosphates.

PMID- 1389154
TI  - A PCR-based method of identifying species-specific repeated DNAs.
AB  - A PCR-based method is described to facilitate the identification of DNA fragments
      that are highly repeated and species-specific. The precision of the technique was
      demonstrated by cloning a fragment that occurred in a high number of copies in
      the plant species Medicago granadensis but in a low number of copies in 17 other
      Medicago species and Melilotus officinalis. This method should greatly accelerate
      the isolation and cloning of short and long interspersed nuclear elements with
      species-specific distributions. Such clones should prove useful in studies of
      phylogenetic relationships in the identification of interspecific hybrids, as in
      situ chromosome markers and other applications.

PMID- 1389155
TI  - Presence of single-stranded DNA in PCR products of slow electrophoretic mobility.
AB  - PCR products were characterized by electrophoresis, blotting and hybridization.
      In addition to the bands of expected size, bands of slower electrophoretic
      mobility were often detected. The slower bands completely disappeared when the
      PCR products were subjected to slow cooling, treated with S1 nuclease or run on
      an alkaline gel, whereas the bands of expected size were unaffected. The slower
      bands are therefore likely to contain single-stranded DNA.

PMID- 1389156
TI  - Subcloning using simplified adaptor addition.
AB  - A simplified procedure for the addition of synthetic oligonucleotide adaptors to
      subclone DNA fragments with incompatible ends is presented. An organophosphate
      degradation gene on a PstI fragment was cloned into the HindIII site of the
      fungal vector pH1S. The opd gene specifies parathion hydrolase and was first
      isolated from a Flavobacterium sp. The gene was present in 12% of the plasmids
      recovered and was inserted in either direction with similar frequencies: 53% with
      the opd start codon distal to the single SalI site of pH1S and 47% in the other
      orientation. All enzymatic steps were carried out in a single microconcentrator
      eliminating DNA loss through manipulation and transfer. Normally, during adaptor
      or linker addition, a larger number of oligonucleotides are attached at each end
      of the insert DNA and must be removed before cloning. The need for enzymatic
      digestion to remove excess adaptors was avoided. Traditional methods have
      utilized phenol/chloroform extraction, ethanol precipitation, gel filtration
      chromatography, spermine precipitation, or preparative gel electrophoresis.
      Eliminating these steps resulted in a simpler, more reliable procedure.

PMID- 1389157
TI  - A simple method for the preparation of single-stranded polydeoxynucleotides of
      desired length.
AB  - A method for the preparation of homogeneous, single-stranded polydeoxynucleotides
      of desired length up to 800 bases is described. The procedure entails 1)
      generation of double-stranded DNA of desired length by PCR using a pair of
      primers of which one is biotinylated and the other is either unlabeled or
      fluorescently labeled, 2) isolation of PCR products by agarose slab gel
      electrophoresis, 3) recovery of desired product by electroelution, 4) binding of
      the product to streptavidin-coated magnetic beads and is followed by 5) duplex
      denaturation and removal of the unbound single strand that is either unlabeled or
      fluorescently labeled. Final product characteristics were determined by capillary
      gel electrophoresis with fluorescence detection. Up to microgram quantities of
      homogeneous single-stranded DNA of a desired length were obtained. These can be
      used as single-stranded size standards in capillary gel electrophoresis
      experiments as well as in other techniques requiring such standards.

PMID- 1389158
TI  - PCR-based analysis of the T-cell receptor V beta multigene family: experimental
      parameters affecting its validity.
AB  - The validity of semiquantitative, PCR-based analysis of gene expression within a
      multigene family, the human T-cell receptor (TCR) beta chain variable region
      family, was investigated. Primer comparability was addressed by grouping
      hybridization temperatures and limiting the size range of amplified fragments.
      Primers selected satisfied criteria for comprehensiveness, match to targets and
      discrimination of nontargets. Specificity was enhanced by maximizing mismatches
      with nontargets and using an elevated hybridization temperature. Reaction
      conditions are described that ensure specificity while maintaining sensitivity.
      Several results confirmed primer specificity. Limits on precision were
      documented: probable error was 3%-7% of mean value for target prevalences (% of
      all TCR mRNA represented by a particular V beta) in the 5%-40% range. Accuracy
      was limited by the nonlinear relationship between target prevalence and signal
      obtained. Because of this relationship, the effect of the observed limits of
      precision varied. Valid distinctions were possible between sufficiently separated
      prevalences, i.e., 0%-1%, 3%-5%, 10%, 30%, greater than 50%. Additional concerns
      addressed include: standardization of signals, coamplifiation and effects of
      primer artifacts, and the nature of the mRNA pool. Only when theoretical and
      practical limits in precision and accuracy are acknowledged can semiquantitative,
      PCR-based analysis be used with confidence to assess gene usage within a large,
      multigene family.

PMID- 1389159
TI  - Heat-soaked PCR: an efficient method for DNA amplification with applications to
      forensic analysis.
AB  - Heat-soaked PCR (HS-PCR) is a method for enhancing amplification performed by
      heating the DNA sample at 94 degrees C in 90 microliters 1.1 x buffer for 30 min.
      A 10-microliters bolus of concentrated (10x) deoxynucleotides, Taq DNA polymerase
      and primers prepared without buffer is then added just prior to thermal cycling.
      We have investigated the application of this method in a variety of forensically
      important DNA samples and compared it with regular PCR (R-PCR). DNA samples
      extracted from bone, postmortem tissues, bloodstains and hair contained low
      concentrations of human DNA or were contaminated with either non- human DNA or
      hemoglobin degradation products. Optimal conditions for HS-PCR were determined
      for the 3' ApoB VNTR locus and applied to a centromeric repeat element and to a
      single-copy locus. HS-PCR consistently and reproducibly enhanced product yield
      and specificity over R-PCR at all three loci in the entire set of DNA samples. HS
      PCR was also effective in overcoming the inhibitory effect of hemoglobin at
      concentrations that fully impeded R-PCR.

PMID- 1389160
TI  - Analysis of mixed human/microbial DNA samples: a validation study of two PCR AMP
      FLP typing methods.
AB  - The reliability of the PCR technique used to type two human variable number
      tandem repeats, that is, 3' to apolipoprotein B gene and locus D17S30, was
      examined using DNA samples of mixed human and microbial origin. Mixtures of human
      and microbial DNA were amplified, choosing microbes found commonly in the vagina.
      Total inhibition of human amplification and/or "drop-out" of the larger
      amplification fragment length polymorphism allele was observed at both loci in
      the presence of DNA from some vaginal micro-flora.

PMID- 1389161
TI  - Improved efficiency in determining the titer of the Autographa californica
      baculovirus nonoccluded virus.
AB  - An economical and time-efficient method for titering the Autographa californica
      multiple-embedded nuclear polyhedrosis virus (AcMNPV) by the endpoint method is
      described. The method uses an electronic pipetting device to perform dilutions in
      the same 60-well microplate as is used for the assay, thus eliminating the need
      for test tubes or vials for making dilutions. Additionally, since small volumes
      are used for the dilutions, a substantial savings in medium is achieved. The
      effect of using three different lepidopteran cell lines in this assay for AcMNPV
      is also described. This test revealed that one line (the Trichoplusia ni IPLB-TN
      R2 line) is at least 1.5 logs more sensitive to AcMNPV when using occlusion body
      formation as the measure of infection. The titer was about 6- to 12-fold higher
      in the IPLB-TN-R2 cell line than the other two lines when plaque assay procedures
      were used. The titer of a recombinant baculovirus with a bacterial beta
      galactosidase gene was also measured in the three cell lines using X-gal as an
      indicator and showed the IPLB-TN-R2 line to be fourfold more sensitive to this
      virus.

PMID- 1389162
TI  - Efficient purification of PCR products using ultrafiltration.
AB  - The use of disposable ultrafiltration devices for the purification of PCR
      amplified DNA products from the other components of the reaction mixture is
      outlined. The advantages of using a 100,000 molecular weight cutoff membrane are
      discussed. The integrity of the membrane-purified DNA is checked by its
      successful use in sequencing, ligation and cloning procedures.

PMID- 1389163
TI  - Ultrathin DNA sequencing gels using microtrough vertical electrophoresis plates.

PMID- 1389164
TI  - Increasing the efficiency and economy of the chemiluminescent detection of DNA.

PMID- 1389165
TI  - Site-specific mutagenesis of almost any plasmid using a PCR-based version of
      unique site elimination.

PMID- 1389166
TI  - Rapid analysis of yeast transformants using colony-PCR.

PMID- 1389167
TI  - Salt-dependent formation of DNA/protein complexes in vitro, as viewed by the gel
      mobility shift assay.

PMID- 1389169
TI  - Minipreparations of plasmid DNA directly from cell culture by the boiling method.

PMID- 1389168
TI  - Simplified drying of polyacrylamide gels for fluorography.

PMID- 1389170
TI  - Rapid and inexpensive micro-electroelution of nucleic acid and protein from
      agarose and polyacrylamide gels.

PMID- 1389171
TI  - Eukaryotic cells grown on microcarrier beads offer a cost-efficient way to
      propagate Chlamydia trachomatis.
AB  - The use of microcarrier cell culture as a method for the in vitro propagation of
      the obligate intracellular bacterial parasite, Chlamydia trachomatis, is
      described. The microcarrier beads proved to be a more cost-effective means to
      propagate C. trachomatis than traditional tissue culture flasks or roller bottles
      without sacrificing yields or infectivity. In addition, microcarrier cell culture
      was found to be a much simpler technique to study the intracellular development
      of these bacteria.

PMID- 1389172
TI  - Improved method for screening cDNA expression libraries for DNA-binding proteins.
AB  - The ability to successfully screen a lambda gt11 cDNA expression library for
      specific gene products that can bind to selected sequences of DNA depends on
      radioactive double-stranded DNA probes with high specific activity. We
      demonstrate here that probes labeled by the PCR are superior to probes made by
      the Klenow reaction. The use of these PCR-generated probes have facilitated our
      efforts to isolate recombinant phage containing putative DNA-binding gene
      products that recognized a 246-base pair transcriptional enhancer region of Rous
      sarcoma virus long terminal repeat.

PMID- 1389173
TI  - Analysis of heat-denatured DNA using native agarose gel electrophoresis.
AB  - The use of native or neutral gels to resolve denatured DNA affords a rapid and
      convenient analytical method for assessing the consequences of a number of
      procedures employed in molecular biology research. We demonstrate that this
      method can be used to analyze transition melting temperature (Tm) and strand
      breakage in heat-denatured duplex DNA. This shows that some commonly recommended
      denaturation procedures can result in significant degradation of DNA and that
      reannealing or aggregation can occur when samples are concentrated or ionic
      conditions altered.

PMID- 1389174
TI  - Multipurpose vectors for peptide expression on the M13 viral surface.
AB  - We have developed a set of three cloning vectors for the expression of
      polypeptides on the surface of the M13 viral coat. The M13mp8 genome has been
      engineered for expression of foreign protein sequences near the NH2-terminus of
      the mature pIII protein, which is present in five copies on the outside of each
      M13 viral particle. All three of the vectors carry the same two useful
      restriction sites for directed cloning of inserts in the pIII coding region; in
      addition, one vector carries the bacterial gene conferring resistance to the
      antibiotic tetracycline, and another expresses the lacZ' polypeptide that allows
      functional complementation of beta-galactosidase activity within the host
      bacterial cell. All of these vectors propagate well in E. coli DH5 alpha F' cells
      and do not require helper phage. We demonstrate that a bacteriophage, expressing
      an eleven amino acid epitope (from human c-myc) at the NH2-terminus of pIII in
      one of our vectors, can be purified from a vast mixture of other M13 phage
      through panning techniques. In particular, we find that the c-myc-expressing
      viral particles can be easily recovered from phage mixtures with the biotinylated
      form of the monoclonal antibody, 9E10, and streptavidin-coated MagneSphere beads.

PMID- 1389175
TI  - Microplate coagulation assays.
AB  - This report describes the development of microplate-based blood coagulation
      assays. The assays require a kinetic microplate reader to follow changes in
      absorbance at 405 nm caused by the coagulating plasma. Procedures for performing
      prothrombin time and activated partial thromboplastin time tests are described
      with intra- and inter-assay variability of a few percentage points. The
      prothrombin time of normal plasma was 64.5 +/- 3.6 s, and the activated partial
      thromboplastin time was 69.8 +/- 3.2 s. Clotting times were prolonged when normal
      plasma was mixed with plasmas deficient in particular coagulation factors, as
      expected. These assays take advantage of the microplate format (small sample size
      and multiple simultaneous assays) and can be customized for specific purposes,
      such as quantifying purified factor IX or assessing protein C activity in plasma.

PMID- 1389176
TI  - Complete one-hour immunocytochemistry based on capillary action.
AB  - We describe a less than one-hour manual method for immunocytochemical analyses of
      B5 or formalin-fixed, paraffin-embedded tissue sections. The method employs
      capillary action to sequentially apply, incubate and remove liquid reagents from
      apposed pairs of up to 20 glass microscope slides and allows for simultaneous
      immunocytochemical analyses of as many as 10 different antigens. The method
      described here uses a) positively charged glass slides to rapidly immobilize
      tissue sections; b) rapid deparaffinization techniques; c) multipurpose reagents;
      d) ethanol-enriched buffer washes to improve capillary action and reduce
      nonspecific background; e) a single broad spectrum streptavidin-peroxidase or
      streptavidin-alkaline phosphatase detection system that identifies most primary
      monoclonal and polyclonal antibodies; and f) specific immunocytochemical signal
      amplification by cyclic chromogen enhancement.

PMID- 1389177
TI  - Quantitation of targets for PCR by use of limiting dilution.
AB  - We describe a general method to quantitate the total number of initial targets
      present in a sample using limiting dilution, PCR and Poisson statistics. The DNA
      target for the PCR was the rearranged immunoglobulin heavy chain (IgH) gene
      derived from a leukemic clone that was quantitated against a background of excess
      rearranged IgH genes from normal lymphocytes. The PCR was optimized to provide an
      all-or-none end point at very low DNA target numbers. PCR amplification of the N
      ras gene was used as an internal control to quantitate the number of potentially
      amplifiable genomes present in a sample and hence to measure the extent of DNA
      degradation. A two-stage PCR was necessary owing to competition between leukemic
      and non-leukemic templates. Study of eight leukemic samples showed that
      approximately two potentially amplifiable leukemic IgH targets could be detected
      in the presence of 160,000 competing non-leukemic genomes. The method presented
      quantitates the total number of initial DNA targets present in a sample, unlike
      most other quantitation methods that quantitate PCR products. It has wide
      application, because it is technically simple, does not require radioactivity,
      addresses the problem of excess competing targets and estimates the extent of DNA
      degradation in a sample.

PMID- 1389178
TI  - Protecting researchers from instrument biohazards.
AB  - The prevention and control of biohazards arising from the use of laboratory
      instruments have become increasingly important in clinical and research
      applications. Centrifuges can be susceptible to contamination because of intense
      wear on primary containers (specimen tubes and bottles), worn O-ring container
      seals, or rotors and buckets lacking tight seals. A recent study by the Center
      for Applied Microbiology and Research, Porton Down, UK, has determined the
      biological safety of certain rotors in various speed ranges. This paper presents
      and discusses these findings.

PMID- 1389179
TI  - Human amyloid precursor protein ameliorates behavioral deficit of flies deleted
      for Appl gene.
AB  - Drosophila amyloid precursor protein-like (Appl) gene encodes a protein product
      (APPL) similar to beta-amyloid precursor protein (APP) associated with
      Alzheimer's disease. To understand the in vivo function of APPL protein, we have
      generated flies deleted for the Appl gene. These flies are viable, fertile, and
      morphologically normal, yet they exhibit subtle behavioral deficits. We show that
      a fast phototaxis defect in Appl- flies is partially rescued by transgenes
      expressing the wild-type, but not a mutant, APPL protein. We further demonstrate
      a functional homology between APPL and APP, since transgenes expressing human APP
      show a similar level of rescue as transgenes expressing fly APPL.

PMID- 1389180
TI  - Suppression of MAP2 in cultured cerebellar macroneurons inhibits minor neurite
      formation.
AB  - We show here that antisense MAP2 oligonucleotides inhibit neurite outgrowth in
      cultured cerebellar macroneurons. Unlike control neurons, which first extend a
      lamellipodial veil followed by a consolidation phase during which the cells
      extend minor neurites, MAP2-suppressed cells persist with lamellipodia and later
      become rounded. The induction of microtubules containing tyrosinated tubulin,
      which parallels neurite outgrowth in control neurons, was blocked under antisense
      conditions. The small but significant increase in acetylated microtubules was not
      affected. In contrast, the suppression of tau, which selectively blocks axonal
      elongation, completely prevented the increase of acetylated microtubules, but did
      not modify the induction of labile microtubules. These results suggest that MAP2
      and tau have different functions: the initial establishment of neurites depends
      upon MAP2, whereas further neurite elongation depends upon tau and microtubule
      stabilization.

PMID- 1389181
TI  - Cellular targets and trophic functions of neurotrophin-3 in the developing rat
      hippocampus.
AB  - The expression of the neurotrophins and trk receptors in the hippocampus has
      directed attention toward their roles in the development and maintenance of this
      region. We have examined the effects of the neurotrophins NT-3, BDNF, and NGF in
      cultures of developing rat hippocampal cells by two criteria: rapid induction of
      c-fos and neurotrophic responses. The selective induction of c-fos mRNA suggests
      the presence of functional receptors for NT-3 and BDNF, but not NGF, in embryonic
      hippocampal cultures. The NT-3-responsive cells were localized in pyramidal
      neurons of areas CA1 through CA3 and dentate granular and hilar cells of
      postnatal organotypic slices, as detected by c-Fos immunocytochemistry. In
      addition to immediate early responses, NT-3 caused a 10-fold increase in the
      number of cells expressing the neuronal antigen calbindin-D28k. This increase was
      dose dependent, with maximal stimulation at 10 ng/ml. In contrast, BDNF elicited
      small but significant calbindin responses. These results indicate biological
      responses to NT-3 in the CNS and suggest roles for for this neurotrophin during
      hippocampal neurogenesis.

PMID- 1389182
TI  - Protein kinase C couples membrane excitation to acetylcholine receptor gene
      inactivation in chick skeletal muscle.
AB  - The signaling pathway connecting membrane depolarization and gene activity in
      skeletal muscle remains largely unknown. Using transcription elongation (run-on)
      analysis we have found that electrical stimulation of denervated chick skeletal
      muscle in vivo rapidly and selectively results in inactivation of acetylcholine
      receptor (AChR) subunit genes. We have studied the possible involvement of
      protein kinase C (PKC) in this response and have observed that electrical
      stimulation increases the activity of PKC in the nucleus by over two orders of
      magnitude within 10 min; phorbol esters, within minutes after intramuscular
      application, block AChR subunit genes in the absence of electrical activity; and
      the activity-triggered gene inactivation is blocked by the protein kinase
      inhibitor staurosporine or by enzyme depletion resulting from chronic
      pretreatment of muscle with phorbol esters. We conclude that PKC is an integral
      component of the pathway coupling membrane excitation and AChR gene control.

PMID- 1389183
TI  - The alpha 5 gene product assembles with multiple acetylcholine receptor subunits
      to form distinctive receptor subtypes in brain.
AB  - The acetylcholine receptor (AChR) alpha 5 gene has been classified as a member of
      the AChR gene family based on sequence homology. Expression studies, however,
      have yet to identify a function for the alpha 5 gene product or even to
      demonstrate an interaction with known AChR subunits. We report here that the
      alpha 5 gene product is identical to the 49 kd protein previously found on
      immunoblots of AChRs purified from brain and ciliary ganglia. In brain the alpha
      5 gene product is present both in alpha 3- and in alpha 4-based receptor
      subtypes, while in the ganglion it is found in an alpha 3-based receptor subtype
      concentrated in postsynaptic membrane. Immunoprecipitation experiments with
      subunit-specific monoclonal antibodies indicate that some native AChRs are likely
      to have at least three kinds of subunits, with two being of the alpha type. These
      findings support new views about the construction of AChRs in neurons.

PMID- 1389184
TI  - An intrinsic neuronal defect operates in dystonia musculorum: a study of
      dt/dt<==>+/+ chimeras.
AB  - In the mouse mutant dystonia musculorum (dt), peripheral and central sensory
      axons develop focal swellings and degenerate. To identify the primary cellular
      target of the mutation, we have analyzed the spinal cords of dt/dt<==>+/+
      aggregation chimeras. In these chimeras, characteristic swellings appeared only
      on the axons of mutant genotype neurons; the axons of wild-type neurons,
      identified by their expression of a transgene-encoded human neurofilament
      protein, were normal. This direct correlation of genotype and phenotype indicates
      that the dt mutation acts via a mechanism intrinsic to affected neurons. In
      addition, we show here that the dt mutation leads to a disorder of neurofilament
      processing in which phosphorylated neurofilament epitopes accumulate
      inappropriately in neuronal perikarya.

PMID- 1389186
TI  - Anesthesia in the desert: experiences with the U.S. Marines during the Persian
      Gulf conflict.

PMID- 1389185
TI  - Dorsal root ganglion neurons expressing trk are selectively sensitive to NGF
      deprivation in utero.
AB  - In utero immune deprivation of the neurotrophic molecule nerve growth factor
      (NGF) results in the death of most, but not all, mammalian dorsal root ganglion
      (DRG) neurons. The recent identification of trk, trkB, and trkC as the putative
      high affinity receptors for NGF, brain-derived neurotrophic factor, and
      neurotrophin-3, respectively, has allowed an examination of whether their
      expression by DRG neurons correlates with differential sensitivity to immune
      deprivation of NGF. In situ hybridization demonstrates that virtually all neurons
      expressing trk are lost during in utero NGF deprivation. Most, if not all,
      neurons expressing trkB and trkC survive this treatment. In contrast, the low
      affinity NGF receptor, p75NGFR, is expressed in both NGF deprivation-resistant
      and -sensitive neurons. These experiments show that DRG neurons expressing trk
      require NGF for survival. Furthermore, at least some of the DRG neurons that do
      not require NGF express the high affinity receptor for another neurotrophin.
      Finally, these experiments provide evidence that trk, and not p75NGFR, is the
      primary effector of NGF action in vivo.

PMID- 1389187
TI  - Patients' assessment of ambulatory anesthesia and surgery.
AB  - STUDY OBJECTIVE: To obtain patients' assessments of ambulatory anesthesia and
      surgery using a return-mail questionnaire postcard. DESIGN: Return-mail
      questionnaire given to consecutive ambulatory surgery patients. SETTING: Adult
      ambulatory surgery unit of a university hospital. PATIENTS: The questionnaire was
      given to 3,722 patients. Responses were returned by 1,511 patients (41%). Among
      the respondents, 95% had gynecologic procedures and 5% had general surgical
      procedures. MEASUREMENTS AND MAIN RESULTS: Eighty-six percent of respondents
      reported at least one minor sequela persisting after discharge. Laparoscopy
      patients experienced significantly more aches, drowsiness, dizziness, sore
      throat, nausea, and vomiting. For all patients, sequelae lasted 1 day for 59% of
      all patients, 2 days for 28%, and 3 or more days for 14%. Different sequelae had
      different durations. Thirty-eight percent of respondents were able to return to
      their usual activities the day after surgery; the remainder required 3.2 +/- 2.0
      additional days. The main reasons for delayed recovery included general malaise
      (57%) and surgical discomfort (38%). Assessing their overall satisfaction, 97%
      would choose day surgery again. CONCLUSIONS: Return-mail questionnaires can be
      used for patient follow-up after ambulatory surgery, with limitations
      characteristic of unselected-patient methods. Patients' assessments of their
      anesthesia and surgery can identify common sequelae that ambulatory patients
      should realistically expect to experience.

PMID- 1389188
TI  - Intraoperative autologous blood salvage with cardiac surgery: an analysis of five
      years' experience in more than 3,000 patients.
AB  - STUDY OBJECTIVE: To analyze intraoperative autologous salvage of shed mediastinal
      blood and subsequent transfusion in cardiac surgery. DESIGN: Retrospective
      statistical analysis. SETTING: University hospital. PATIENTS: Three thousand
      twenty two patients undergoing cardiac surgery from 1984 to 1988. INTERVENTIONS:
      A review of anesthesia and transfusion records of all patients who underwent
      intraoperative salvage of shed blood and autologous transfusion using the
      Sorenson Receptal Auto Transfusion System (ATS) with saline wash prior to
      reinfusion in cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The salvaged blood
      volume ranged from 36 to 2,795 ml, with a mean of 321 +/- 222 ml (SD). Eighteen
      percent of patients did not receive any homologous blood products during their
      hospitalization. Patients who received only salvaged autologous transfusion were
      younger, had higher preoperative hemoglobin and hematocrit values, had a larger
      body surface area, and had shorter surgeries compared with patients who received
      only homologous blood or both autologous and homologous blood. More blood
      products were given to patients who received salvaged autologous blood compared
      with those who did not. Patients who underwent normovolemic hemodilution prior to
      extracorporeal circulation with subsequent reinfusion received significantly
      fewer blood products. Ten preoperative and four intraoperative variables
      significantly influenced the salvaged volume. Previous cardiac surgery was the
      most significant preoperative variable, and repair of ventricular septal defect
      produced by myocardial ischemia was the most significant intraoperative variable.
      CONCLUSION: Considering the average salvaged volume and its current autologous
      transfusion-related expense, autologous blood salvage is potentially an economic
      benefit. Perioperative blood conservation requires a considerable commitment from
      surgeons, anesthesiologists, perfusionists, and intensive care physicians to be
      effective.

PMID- 1389189
TI  - Attenuation of hypertensive response to tracheal intubation with nitroglycerin.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and safety of intravenous (IV)
      nitroglycerin in attenuating the hypertensive response to laryngoscopy and
      intubation as a new application of the drug. DESIGN: Controlled, randomized,
      double-blind study. SETTING: University hospital. PATIENTS: Thirty normotensive
      patients (ASA physical status I) undergoing elective surgery were divided into
      three groups of ten patients each. INTERVENTIONS: Anesthesia was induced with
      thiopental sodium 5 mg/kg i.v., and tracheal intubation was facilitated with
      vecuronium 0.2 mg/kg i.v. During anesthesia, ventilation was assisted or
      controlled with 1% enflurane and 50% nitrous oxide in oxygen. Either 1.5
      micrograms/kg of nitroglycerin, 2.5 micrograms/kg of nitroglycerin, or saline
      (control) was administered IV simultaneously with the start of laryngoscopy
      (lasting 30 seconds), which was attempted 2 minutes after administration of
      thiopental sodium and vecuronium. MEASUREMENTS AND MAIN RESULTS: Patients
      receiving saline showed a significant increase in mean arterial pressure and rate
      pressure product associated with tracheal intubation. These increases following
      tracheal intubation were significantly reduced in nitroglycerin-treated patients
      compared with those in the control group (p < 0.05). CONCLUSION: A single, rapid
      IV dose of nitroglycerin is a simple, practical, effective, and safe method to
      attenuate the hypertensive response to laryngoscopy and tracheal intubation.

PMID- 1389190
TI  - Three balanced anesthetic techniques for neuroanesthesia: infusion of thiopental
      sodium with sufentanil or fentanyl compared with inhalation of isoflurane.
AB  - STUDY OBJECTIVE: To compare emergence from anesthesia and the hemodynamic and
      respiratory depressant effects of thiopental sodium infusion plus sufentanil or
      fentanyl with those of isoflurane as the primary component of a balanced
      technique for neuroanesthesia. DESIGN: Randomized, double-blind, prospective
      study. SETTING: University hospital and its affiliated Veterans Affairs Medical
      Center. PATIENTS: Thirty patients undergoing elective craniotomy for aneurysm or
      tumor. INTERVENTIONS: Thiopental with infusion of sufentanil 0.1 microgram/kg/hr,
      thiopental with infusion of fentanyl 1 microgram/kg/hr, or inhalation of 0.25% to
      2% isoflurane as the major component of a balanced anesthesia technique that
      included nitrous oxide (N2O) and vecuronium (potency ratio of sufentanil to
      fentanyl, 10:1). MEASUREMENTS AND MAIN RESULTS: Intraoperative stress response
      (as indicated by intraoperative hypertension) was said to be the percentage of
      time the patient required administration of an antihypertensive drug, measuring
      from the first dose of thiopental to discontinuation of N2O at the end of the
      procedure, excluding any period of induced hypotension. Rapidity of emergence was
      measured by the number of minutes from discontinuation of N2O to first opening of
      the eyes on command. Adequacy of spontaneous ventilation was evaluated by
      determining partial pressure of arterial carbon dioxide 1, 2, and 3 hours after
      discontinuation of N2O. Extent of vasoactive drug administration for control of
      intraoperative hypertension (as determined by the clinicians caring for the
      patients) was described by minutes of vasodilator infusion and milligrams of
      propranolol or labetalol administered. The frequency of postoperative
      hypertension was defined as the number of patients in each group who required
      medication for postoperative hypertension. No significant differences in
      variables were found for thiopental/sufentanil, thiopental/fentanyl, or
      isoflurane when these drugs were used with N2O and vecuronium. CONCLUSIONS: Any
      one of these balanced anesthetic techniques appears appropriate for craniotomy.

PMID- 1389191
TI  - Elderly patients recover more rapidly from desflurane than from isoflurane
      anesthesia.
AB  - STUDY OBJECTIVE: To compare the hemodynamic, emergence, and recovery
      characteristics of desflurane-nitrous oxide (N2O) anesthesia with those of
      isoflurane-N2O anesthesia in elderly patients. DESIGN: Randomized study. SETTING:
      Main operating room of a major U.S. teaching hospital. PATIENTS: Thirty-four ASA
      physical status II and III patients aged 65 or older undergoing surgical
      procedures of greater than 1 hour duration. INTERVENTIONS: Group 1 (17 patients)
      received desflurane in 60% N2O for their surgical procedure. Group 2 (17
      patients) received isoflurane in 60% N2O. Thiamylal 2 mg/kg administered
      intravenously (IV) induced anesthesia, and succinylcholine 1.5 mg/kg i.v.
      facilitated intubation. Muscle relaxation was maintained with vecuronium.
      Titration of the anesthetics maintained hemodynamics to within 20% of the
      patients' preinduction values. MEASUREMENTS AND MAIN RESULTS: Measurement of
      hemodynamics occurred every 2 minutes prior to skin incision and every 5 minutes
      thereafter. The times for discontinuation of inhaled anesthetics to eye opening,
      hand grip on command, and recall of name and date of birth were measured in a
      standardized fashion for both groups. The time to discharge from the
      postanesthesia care unit (PACU) was determined by a blinded PACU nurse using
      standard published criteria. The two groups did not differ with respect to
      demographics, hemodynamic stability, and times to eye opening (5 +/- 3 minutes
      for desflurane vs. 8 +/- 4 minutes for isoflurane), hand grip on command (9 +/- 4
      minutes vs. 12 +/- 1 minutes), and recall of name and date of birth (13 +/- 8
      minutes vs. 12 +/- 7 minutes). The median duration of PACU stay was significantly
      shorter (p < 0.03) in the desflurane group (80 minutes) compared to the
      isoflurane group (128 minutes). CONCLUSIONS: Desflurane may benefit elderly
      patients by providing a more rapid recovery from anesthesia, leading to a shorter
      PACU stay.

PMID- 1389192
TI  - Lidocaine inhalation attenuates the circulatory response to laryngoscopy and
      endotracheal intubation.
AB  - STUDY OBJECTIVE: To evaluate the effect of lidocaine inhalation on the
      circulatory response to direct laryngoscopy and endotracheal intubation. DESIGN:
      Prospective, randomized study. SETTING: Operating theater at a public hospital.
      PATIENTS: Eighty patients (ASA physical status I and II ages 25 to 45 years)
      scheduled for major abdominal surgery. INTERVENTIONS: In the first stage, 40
      patients were randomly assigned to receive inhalation of either lidocaine 40 mg
      or a 0.9% solution of sodium chloride (placebo). In the second stage, the next 20
      consecutive patients received inhalation of lidocaine 120 mg, and another 20
      consecutive patients received intravenous (IV) lidocaine 1 mg/kg. MEASUREMENTS
      AND MAIN RESULTS: Mean arterial pressure rose significantly in the i.v. lidocaine
      group (21.2 mmHg; p < 0.05), the saline inhalation group (29.2 mmHg; p < 0.05),
      and the lidocaine 40 mg inhalation group (22.9 mmHg; p < 0.05), but not in the
      lidocaine 120 mg inhalation group (10.1 mmHg). The heart rate (HR) response to
      intubation with lidocaine inhalation was dose dependent. In the saline inhalation
      group, HR increased by 15.6 beats per minute (bpm) (p < 0.05); in the lidocaine
      40 mg inhalation group, HR increased by 9.1 bpm (p < 0.05); and in the lidocaine
      120 mg inhalation group, HR increased by only 3.1 bpm. CONCLUSION: Inhalation of
      lidocaine 120 mg prior to induction of anesthesia is an effective, safe, and
      convenient method to attenuate the circulatory response to laryngoscopy and
      endotracheal intubation.

PMID- 1389193
TI  - Are automated anesthesia records better?
AB  - STUDY OBJECTIVE: To determine whether data recorded by an information management
      system is significantly different from that recorded manually. DESIGN: A
      comparison was made between 13 handwritten and 13 computer-generated anesthesia
      records by calculating the frequency with which recorded variables were outside
      predetermined acceptable ranges. Five physiologic variables [systolic blood
      pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), end-tidal
      partial pressure of carbon dioxide (PETCO2), and oxygen saturation by pulse
      oximeter (SpO2)] were compared during the initial 1 1/2 hours of operation.
      SETTING: Surgical suite at a university-affiliated hospital. PATIENTS: Thirteen
      adult patients scheduled for operations that required general anesthesia for
      longer than 1 1/2 hours. INTERVENTION: In addition to the traditional handwritten
      anesthesia records, an information management system (ARKIVE Patient Management
      System, DIATEK, San Diego, CA) was used to collect data from each case.
      MEASUREMENTS AND MAIN RESULTS: No significant differences were found between the
      methods in the frequency of elevated SBP, elevated DBP, and tachycardia. However,
      the manual records showed low SBP, DBP, and HR with a significantly lower
      frequency (2%, 11%, 1%, respectively) than the automated records (6%, 26%, 5%,
      respectively; p < 0.01). The automated PETCO2 readings were higher than the upper
      limit (40 mmHg) with a higher frequency (18%) than the manual records (3%; p <
      0.01). On the automated records, SpO2 was noted to be 90% or less on two
      occasions, but significant desaturation was noted only once on the manual charts.
      CONCLUSIONS: Observer bias, missed readings, and errors of memory, which affect
      manual anesthetic records, may cause significant inaccuracy and may be avoided by
      using automated records generated by information management systems.

PMID- 1389194
TI  - Butorphanol for the relief of shivering associated with extradural anesthesia in
      parturients.
AB  - STUDY OBJECTIVE: To assess the efficacy of butorphanol for the relief of
      shivering following the epidural administration of 2% lidocaine. DESIGN:
      Randomized, double-blind study. SETTING: Labor and delivery department of a
      university-affiliated hospital inpatient facility. PATIENTS: Sixty-one healthy
      labor patients. INTERVENTIONS: Patients who had sustained shivering associated
      with lidocaine epidural anesthesia were given normal saline or butorphanol 1 mg.
      Patients were observed for 20 minutes following the administration of a study
      solution. MEASUREMENTS AND MAIN RESULTS: Shivering ceased within a mean time of
      12.9 +/- 3.8 minutes in approximately 81% of the patients who received epidural
      butorphanol (p < 0.01), while 3% of the patients in the placebo group had no
      shivering following the administration of epidural saline. No sedation or changes
      in fetal heart rate were associated with epidural butorphanol. CONCLUSIONS:
      Epidural butorphanol is effective in the treatment of postepidural shivering
      associated with epidural lidocaine. Epidural agonist opioids have been reported
      to be efficacious in the management of postepidural shivering. This study
      demonstrated that a partial agonist opioid also is effective in the treatment of
      postepidural shivering.

PMID- 1389195
TI  - Blind oral intubation: the development and efficacy of a new approach.
AB  - STUDY OBJECTIVE: To develop an approach to blind oral intubation. With the aid of
      a fiberoptic laryngoscope and stylet within an endotracheal tube, a video camera,
      a monitor, and a recorder to correlate the effects of various manipulations of
      the airway on access to the trachea, a suitable approach was devised. We then
      evaluated its efficacy. DESIGN: Randomized, prospective comparison of regimens.
      SETTING: Inpatient surgery at a university-affiliated teaching hospital.
      PATIENTS: One hundred adult patients with no known abnormalities of the upper
      airway by history or on physical examination, scheduled to undergo elective
      surgery, and without evidence of major cardiac disease or need for a rapid
      sequence induction of anesthesia. INTERVENTIONS: Fifty patients in each of two
      groups were given fentanyl 5 micrograms/kg intravenously (IV), followed 2 minutes
      later by thiopental sodium 5 mg/kg and succinylcholine 2 mg/kg. Patients in Group
      1 (the controls) were orally intubated via direct laryngoscopy using a Macintosh
      #3 blade. Patients in Group 2 (the experimentals) were intubated orally with the
      approach developed without the use of a laryngoscope. Intubations were deemed
      successful if they were performed within 1 minute after the mouth was opened.
      MEASUREMENTS AND MAIN RESULTS: All the patients in Group 1 were successfully
      intubated within 1 minute, while 49 of the 50 patients in Group 2 were
      successfully intubated within 1 minute. CONCLUSIONS: Blind oral tracheal
      intubation can be successfully performed in a safe and effective manner after
      appropriate teaching of the technique.

PMID- 1389196
TI  - Thoracoabdominal aortic aneurysm repair in a 15-month-old child.
AB  - This case report describes a young child with a thoracoabdominal aortic aneurysm,
      a very rare condition in pediatrics. The anesthetic management for resection of
      the aneurysm and repair of the aorta are presented, and special considerations
      for pediatric patients are discussed.

PMID- 1389197
TI  - Anesthesia for pediatric laparoscopic cholecystectomy.
AB  - We report the general anesthetic events and clinical concerns encountered with a
      laparoscopic cholecystectomy in a 19-month-old toddler. Carbon dioxide was
      insufflated to create a pneumoperitoneum, with resulting intra-abdominal
      pressures ranging from 5 to 11 mmHg. The end-tidal partial pressure of carbon
      dioxide (PETCO2) rose as high as 48 mmHg (a 10 mmHg increase from baseline),
      requiring a 68% increase in minute ventilation to achieve preinsufflation values.
      Careful monitoring of ventilation, PETCO2, and intra-abdominal pressure are
      recommended for optimal anesthetic management of the pediatric laparoscopic
      cholecystectomy patient.

PMID- 1389198
TI  - Use of the Augustine stylet anticipating difficult tracheal intubation in
      Treacher-Collins syndrome.
AB  - Treacher-Collins syndrome is a familial and congenital condition often associated
      with a difficult airway. Although the condition is rare, the anesthesia care
      provider may encounter it on occasion. This report describes a patient with
      Treacher-Collins syndrome scheduled to undergo facial reconstruction (fore-head
      plasty, brow lift, and rhinoplasty) as the sixth of multiple operations. A
      nasotracheal intubation using the stylet component of a recently introduced
      airway device, the Augustine Guide, was successfully performed. This is believed
      to be the first reported use of this method using the Augustine stylet.

PMID- 1389199
TI  - Low back pain following epidural blood patch.
AB  - A patient underwent outpatient knee arthroscopy with spinal anesthesia
      administered at the patient's request. The patient was discharged after a 3-hour
      recovery period. Three days later, the patient returned because of a headache
      that had begun the evening after surgery and progressively worsened. Treatment
      with caffeine and hydration for presumed postdural puncture headache resulted in
      relief for approximately 1 hour. An epidural blood patch was then performed and
      relieved symptoms for 3 hours until backache began and worsened over the next 7
      hours. Computed axial tomography showed epidural air. After symptomatic treatment
      and observation overnight, the patient was released, and follow-up by telephone
      was planned. For 2 days, symptoms persisted. Therapy with aspirin 600 mg 4 times
      daily resulted in acute and significant relief. The backache resolved after 1
      week. A review of the literature on backache following epidural blood patch is
      presented.

PMID- 1389200
TI  - The rational pharmacology of digoxin.
AB  - Although digoxin remains one of the most widely prescribed drugs in the United
      States, potential pharmacodynamic and pharmacokinetic interactions between this
      compound and other drugs, diseases, and events commonly encountered in the
      perioperative period remain largely unappreciated. Furthermore, the therapeutic
      benefit of discontinuing or initiating digoxin treatment preoperatively remains
      unclear. We present a basic review of current knowledge regarding digoxin
      pharmacology and examine those concepts from the perspective of clinical
      anesthesiologists.

PMID- 1389201
TI  - New modalities in postoperative nausea and vomiting.

PMID- 1389203
TI  - Economic impact of anesthesia decision making: they pay the money, we make the
      choice.

PMID- 1389202
TI  - Muscle relaxants for outpatient surgery: old and new.

PMID- 1389205
TI  - Management of patients with acute and chronic pain.

PMID- 1389204
TI  - How to assess quality in ambulatory surgery.

PMID- 1389207
TI  - Intravenous anesthesia of the future.

PMID- 1389206
TI  - Anesthetic infusion techniques--how to do it.

PMID- 1389208
TI  - Cytokine-cytokine interactions in the context of cytokine networking.

PMID- 1389209
TI  - An antibody with specificity for surfactant protein C precursors: identification
      of pro-SP-C in rat lung.
AB  - Surfactant protein C (SP-C) is a lung-specific, hydrophobic peptide found in
      organic extracts of pulmonary surfactant. Alveolar SP-C (3.5 kD) is produced from
      proteolytic cleavage of a larger precursor molecule (pro-SP-C; 21 kD). While SP-C
      is synthesized by type II cells, the pathways for processing and secretion have
      remained elusive due, in part, to the lack of monospecific antibodies against SP
      C or its precursors. This report describes production and characterization of a
      new antibody directed against pro-SP-C epitopes. Polyclonal antisera (anti-CPRO
      SP-C) was prepared using a synthetic peptide corresponding to a portion of rat SP
      C cDNA sequence (Ile26-Ser72). This contained amino acids 3-35 of mature SP-C
      plus additional C-terminal residues (His59-Ser72). On Western blots, anti-CPRO-SP
      C competitively reacted to CPRO-SP-C but not to mature SP-C. Immunoblots of in
      vitro synthesized pro-SP-C confirmed that the antisera also recognized native
      protein. Immunocytochemistry with anti-CPRO-SP-C demonstrated staining for pro-SP
      C peptides in isolated type II cells as well as in alveolar epithelial cells of
      rat lung sections. Pro-SP-C preferentially co-localized to cells that stained
      positive for Maclura pomifera antigen. Anti-CPRO-SP-C staining was not observed
      in lung interstitium, pulmonary vasculature, or several control tissues (brain,
      heart, and liver were negative). Western blotting of subcellular fractions
      demonstrated pro-SP-C peptides in plasma membrane (20 kD) and microsomal (20 and
      21 kD) fractions with a 16 kD peptide present in lamellar bodies. No pro-SP-C
      peptides were detected in purified surfactant. These results demonstrate the use
      of a synthetic peptide to generate specific antiserum against more hydrophilic
      domains of pro-SP-C sequences and confirm that SP-C propeptides are unique to the
      lung.

PMID- 1389210
TI  - Pathways of fibrin turnover of human pleural mesothelial cells in vitro.
AB  - The mesothelium contains both procoagulant and fibrinolytic activities. An
      imbalance between these activities could account for the abnormal fibrin turnover
      and pleural fibrin deposition that is characteristic of pleural inflammation.
      Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to
      tissue factor, and the prothrombinase complex can also assemble at the HPMC
      surface. HPMC express tissue plasminogen activator (tPA) but no detectable
      fibrinolytic activity in a fibrin plate assay. Inhibition of HPMC fibrinolytic
      activity is due, in part, to elaboration of plasminogen activator inhibitors-1
      and -2 (PAI-1 and PAI-2) as well as antiplasmins. Synthesis of PAI-1 and PAI-2 is
      inhibited by actinomycin D and cyclohexamide. HPMC PAI-1 is increased by
      transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF
      alpha), as is tPA release, while PAI-1 mRNA is unchanged and tPA mRNA is
      increased. PAI-2 release is induced by TNF-alpha and TGF-beta. Because they are a
      rich source of PAI-1 and PAI-2, HPMC may contribute to the high levels of these
      inhibitors in pleural exudates. Stimulation of HPMC by TNF-alpha or TGF-beta in
      vitro did not alter HPMC procoagulant activity nor the balance of elevated PAI
      and antiplasmins relative to PA, changes that collectively favor formation and
      persistence of pericellular fibrin.

PMID- 1389211
TI  - Murine hypersensitivity pneumonitis: production and importance of colony
      stimulating factors in the course of a lung inflammatory reaction.
AB  - The release of colony-stimulating factors (CSFs) and their contribution to the
      inflammatory response in the lungs of mice exposed by the intranasal route to the
      actinomycete Faeni rectivirgula (150 micrograms/day, 3 days/wk), an important
      thermophilic actinomycete that determines farmer's lung in humans, was examined.
      Bronchoalveolar lavages (BAL) and lung homogenates of normal mice or saline
      instilled mice contained undetectable levels (less than 0.5 U/ml) of the
      cytokines interleukin-3 (IL-3), colony-stimulating factor-1 (CSF-1), and
      granulocyte/macrophage colony-stimulating factor (GM-CSF). Mice instilled with F.
      rectivirgula developed a CSF cytokine response early (24 h) after the
      instillation that increased and plateaued 2 wk later, and stayed high thereafter.
      Similarly, lung homogenates of F. rectivirgula-challenged mice contained
      significant levels of all three CSFs from 24 h after treatment until termination
      of the experiment. The offending agent itself, F. rectivirgula, was found to
      directly induce the secretion of IL-3 and GM-CSF from isolated mouse BAL cells
      and mouse splenocytes, at doses ranging from 1 to 100 micrograms/ml. This was not
      due to contaminating endotoxin, as inclusion of polymyxin B did not modify this
      release. Instillation of antibodies against the CSFs in mice challenged with F.
      rectivirgula did not modify the increase in BAL cell number determined by the
      challenge (11-fold increase in BAL cell number in F. rectivirgula-instilled mice
      at 3 wk, whether given anti-CSFs or not). Moreover, direct intratracheal infusion
      of CSFs (5,000 U of IL-3/CSF-1/GM-CSF) every week did not change the cellular
      response seen in challenged mice.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389212
TI  - Luminal purinergic regulatory mechanisms of tracheal ciliary beat frequency.
AB  - To investigate the modulation of tracheal ciliary beat frequency (CBFt) by purine
      nucleotides and nucleosides acting on luminal receptors, aerosolized ATP, GTP,
      AMP-PNP, GMP-PNP, adenosine, and guanosine were each administered separately to
      the tracheal lumen in eucapnically ventilated, barbiturate-anesthetized beagles.
      Four studies were conducted in each of seven dogs from a cohort of eight dogs.
      The CBFt responses were measured on the right lateral surface of the mid-trachea
      using heterodyne mode correlation analysis laser light scattering. Aerosolized
      10(-6) M and 10(-5) M ATP stimulated CBFt from the baseline of 5.9 +/- 1.4 Hz to
      maxima of 12.1 +/- 1.4 Hz and 13.3 +/- 1.6 Hz, respectively, while the same
      corresponding ATP-analogue (AMP-PNP) concentrations stimulated baseline CBFt to
      maxima of 12.7 +/- 4.1 Hz and 18.1 +/- 2.1 Hz, respectively. Similarly, 10(-6) M
      and 10(-5) M GTP stimulated baseline CBFt to maxima of 14.8 +/- 1.1 Hz and 12.8
      +/- 4.6 Hz, respectively. The corresponding GTP-analogue (GMP-PNP) concentrations
      stimulated CBFt to maxima of 14.5 +/- 2.1 Hz and 18.8 +/- 4.4 Hz, respectively.
      Prior delivery of 10(-5) M adenosine reduced all these nucleotide-induced
      stimulatory responses. Prior delivery of 10(-5) guanosine partially reduced the
      GTP- and the GMP-PNP-induced stimulatory responses. These data demonstrate that
      nucleotides and nucleosides modulate CBFt through specific P2 and P1 purinergic
      receptors on the luminal surface, thus providing a direct mechanism within the
      airways to enhance the transport of mucus.

PMID- 1389213
TI  - Endotoxin induces the expression of macrophage inflammatory protein 1 alpha mRNA
      by rat alveolar and bone marrow-derived macrophages.
AB  - Macrophage inflammatory protein 1 alpha (MIP-1 alpha) is a newly described
      cytokine that is present in large amounts in the culture supernatant of an
      endotoxin-stimulated murine macrophage-like cell line (RAW 264.7). There is
      increasing information that suggests that this cytokine mediates acute
      neutrophilic inflammation, although the mechanism of mediation is unknown. Data
      examining the production and regulation of MIP-1 alpha by primary rat macrophages
      are lacking, and MIP-1 alpha has not been studied previously in an animal model
      of endotoxin-induced neutrophilic alveolitis. In this study, we performed
      Northern analysis of steady-state rat MIP-1 alpha mRNA using an oligonucleotide
      probe complementary to amino acids 4-13 of murine MIP-1 alpha. Our data
      demonstrate that rat alveolar and bone marrow-derived macrophages can be induced
      by in vitro endotoxin treatment to express a 1.1-kb MIP-1 alpha mRNA. Expression
      of the mRNA could be elicited by treatment with 0.1 to 10.0 micrograms/ml of
      endotoxin in vitro with peak steady-state levels detectable up to 9 h after
      adding endotoxin to the media. Alveolar macrophages recovered by whole lung
      lavage from endotoxin-treated rats expressed increased amounts of the mRNA
      homologous to MIP-1 alpha mRNA when treated in vitro with endotoxin. We also
      found that rat neutrophils could be induced by endotoxin in vitro to express the
      MIP-1 alpha mRNA. We were able to identify MIP-1 alpha in culture supernatant
      from endotoxin-stimulated rat alveolar and bone marrow-derived macrophages by
      immunoprecipitation with a specific goat anti-murine MIP-1 alpha.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1389215
TI  - Sensitivity of contrast ultrasound in the detection of atrial septal defect with
      predominant left-to-right shunting.
AB  - Ultrasound contrast techniques are used widely as a screening test for
      intracardiac shunt. We performed a retrospective analysis of contrast
      echocardiograms in 29 consecutive patients with atrial septal defect (excluding
      Eisenmenger's) proved by cardiac catheterization. A positive (right-to-left
      atrial) ultrasound contrast effect was seen in 25 patients in whom
      catheterization pulmonary-to-systemic flow rate (Qp/Qs) was 2.2 +/- 0.9 (SD).
      Four patients had false-negative contrast echocardiography results; their Qp/Qs
      was 2.9 +/- 0.4 (p = 0.07). The percent left-to-right shunt was higher in the
      group with false-negative contrast echocardiographic results (65% +/- 4% vs 47%
      +/- 21%) (p = 0.05). Shunts with Qp/Qs < or = 2.0 had a sensitivity of 100%,
      whereas those with Qp/Qs > or = 2.1 had a sensitivity of 73%. In the four false
      negative contrast echocardiographic results, three had findings of an atrial
      septal defect by pulsed Doppler, color Doppler, or both. Thus the presence of a
      large left-to-right shunt may decrease the sensitivity of the ultrasound contrast
      technique for the detection of an atrial septal defect. Contrast ultrasonography
      should be used in conjunction with Doppler and two-dimensional echocardiography
      criteria for diagnosis of atrial septal defect.

PMID- 1389214
TI  - The influence of intravenous Albunex injections on pulmonary arterial pressure,
      gas exchange, and left ventricular peak intensity.
AB  - Contrast ultrasonography may be used to assess regional tissue perfusion. The
      purpose of this study was to evaluate the safety and efficacy of a new,
      commercially prepared ultrasound contrast agent (Albunex) in dogs. The injections
      were administered from peripheral intravenous (IV), right atrial (RA), and
      pulmonary artery (PA) sites. Acute pulmonary hemodynamic and gas exchange effects
      of low-dose (0.5, 1.0, 2.0 ml) Phase I injections, and high-dose (2.0, 5.0, 10,
      20 ml) Phase II injections of Albunex were evaluated in nine dogs. Immediately
      before and after each injection, pulmonary artery pressure (PAP) and oxygen
      tension (PO2) were determined. In addition, left ventricular cavity opacification
      was assessed visually and by videodensitometric off-line analysis. Visual
      assessment was performed by four blinded observers who graded on a scale of 0 to
      3 (0 = no contrast enhancement of the left ventricular (LV) cavity; 1 = weak or
      suboptimal contrast enhancement; 2 = optimal or excellent contrast enhancement;
      and 3 = attenuation of the ultrasound signal following a contrast injection).
      Peak pixel intensity was also determined with videodensitometric analysis.
      Results showed that significant changes in PAP or PO2 were not noted after
      Albunex injections, regardless of injection site or dose range. The average
      change in PAP after Albunex injection was 1.0 mm Hg +/- 1.2 mm Hg (NS), and the
      average change in PO2 after Albunex injections was 6.2 mm Hg +/- 6.7 mm Hg (NS).
      The left ventricular cavity peak pixel intensity was dependent on both injection
      site (PA = RA > IV) and dose range (2.0 = 1.0 > 0.5).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1389216
TI  - Value of transesophageal color Doppler echocardiography for detection of
      different types of atrial septal defect in adults.
AB  - In 121 adults, the value of transthoracic and transesophageal color Doppler
      echocardiography for detection of different types of atrial septal defect (ASD)
      or of partial anomalous pulmonary venous return was analyzed. The 121 patients
      had a total of 129 defects with left-to-right atrial shunting (including eight
      patients with two types of defects). All of six cases with primum-type ASD were
      diagnosed correctly by both echocardiographic methods. Ninety-seven patients
      showed a secundum-type ASD during transesophageal echocardiography: by
      transthoracic echocardiography, only eight (20%) of the 40 small defects
      (diameter < 5 mm) were detected as compared with 15 (83%) of the 18 defects with
      a diameter of 5 to 10 mm and all 39 defects with a diameter > 10 mm. A sinus
      venosus--type ASD was evident by transesophageal echocardiography in 11 patients,
      of which only one (9%) was demonstrated by the transthoracic approach. Partial
      anomalous pulmonary venous return was seen by transesophageal echocardiography in
      13 patients but missed in two other patients in whom anomalous pulmonary venous
      return was subsequently identified by surgery (both with anomalous return of the
      upper right pulmonary vein into the superior vena cava). By use of the
      transthoracic technique, partial anomalous venous return was detected in only two
      cases, both of which had "scimitar syndrome." Compared with transthoracic
      echocardiography, the transesophageal approach is clearly superior in the
      detection of small secundum-type ASD, sinus venosus--type ASD, and partial
      anomalous pulmonary venous return.

PMID- 1389217
TI  - Computerized measurement of Doppler flow velocity waveforms: validation of a new
      system.
AB  - Manual measurement of Doppler flow velocity waveforms is time-consuming and
      carries unavoidable and significant intraobserver and interobserver variability.
      Those drawbacks limit the routine use of Doppler-derived indexes of systolic and
      diastolic function. This report describes a system that performs automatically
      all relevant measurements currently obtained from mitral, tricuspid, aortic, and
      pulmonary waveforms. One hundred and sixty waveforms, obtained from patients
      whose ages ranged from a 19-week fetus to a 21-year-old adult, were measured both
      manually and automatically. High correlations were found for all types of
      measurement: r = 0.993 for velocity measurements, r = 0.995 for time interval
      measurements, r = 0.881 for acceleration measurements, r = 0.867 for pressure
      half-time measurements, and r = 0.993 for flow integral measurements. When
      compared with manual measurements, automatized measurements displayed
      significantly lower intraobserver and interobserver variabilities for all types
      of measurements. Finally, the automatized measurement system cuts the time spent
      by a factor of more than five. Such a system of computerized measurements of
      Doppler flow velocity waveforms should become increasingly valuable as both a
      clinical and a research tool.

PMID- 1389218
TI  - Restrictive left ventricular diastolic filling identifies patients with heart
      failure after acute myocardial infarction.
AB  - Left ventricular diastolic filling was characterized by transmitral pulsed-wave
      Doppler velocities in 62 patients with acute myocardial infarction, and diastolic
      filling variables were correlated with the presence of clinical heart failure. At
      the time of admission, 47 patients were free of heart failure and 15 patients
      were in Killip class II to IV. In the latter group of patients with heart
      failure, peak velocity of late filling wave caused by atrial contraction (A) was
      lower (0.48 versus 0.59 m/sec, p < 0.05), ratio of peak velocity of early rapid
      filling wave to peak velocity of late filling wave caused by atrial contraction
      (E/A) was higher (1.5 versus 1.1, p < 0.01), and deceleration time (136 versus
      196 msec, p = 0.0001) was shorter when compared with the patients not in heart
      failure after acute myocardial infarction. Multivariate analysis showed that the
      deceleration time was a powerful independent predictor of presence of heart
      failure after controlling for systolic functional variables. Therefore, diastolic
      filling variables can complement systolic functional variables in the
      identification of the patients with postinfarction left ventricular failure.

PMID- 1389219
TI  - Decreased and abnormal left ventricular filling in acute heart failure: role of
      pericardial constraint and its mechanism.
AB  - Pericardial constraining force is minimal in normal hearts; however, it is
      considered to be prominent in moderate to severe heart failure. Thus, effects of
      the pericardium on pulsed Doppler transmitral flow velocity pattern were examined
      in 17 dogs with acute left ventricular dysfunction. Left ventricular dysfunction
      with left ventricular end-diastolic pressure > or = 15 mm Hg was produced by
      injection of microspheres into the left coronary artery. Transmitral flow
      velocity pattern, left atrial and left ventricular diameters, and high-fidelity
      left atrial and left ventricular pressures were recorded before and after
      pericardiectomy. In five of the 17 dogs, mitral regurgitation with giant "v" wave
      of left atrial pressure occurred with reductions of left ventricular systolic
      pressure and peak rate of the left ventricular pressure fall (dP/dt) after
      pericardiectomy. In the other 12 dogs, peak early and late diastolic filling
      velocities increased with a decrease in left ventricular minimal pressure and
      increases in left arterial and left ventricular diameters and left atrial and
      left ventricular compliance after pericardiectomy. In these 12 dogs, left atrial
      to left ventricular crossover pressure, left ventricular end-diastolic pressure,
      and references for left ventricular relaxation did not change after
      pericardiectomy. Thus the release from pericardial constraining force in severe
      heart failure may increase chamber compliance of the left ventricle and left
      atrium and, in turn, increase peak early and late diastolic filling velocities
      through an increment in forward transmitral pressure gradient. Increased
      pericardial constraining force is a possible cause limiting left ventricular
      filling and hence cardiac output in heart failure.

PMID- 1389221
TI  - Diagnostic pitfalls in transesophageal echocardiography.
AB  - The technology of transesophageal echocardiography is now widely available and
      has proved extremely useful in evaluating cardiovascular anatomy and pathology.
      Unfortunately, the enhanced echocardiographic detail and multiple transesophageal
      imaging planes may sometimes be confusing and cause misinterpretations. The
      majority of these problems are simply the result of operator inexperience. To
      help prevent misdiagnoses, we have collected a series of the more common
      diagnostic and technical "pitfalls" of transesophageal echocardiography.

PMID- 1389220
TI  - Detection of central pulmonary artery thromboemboli by transesophageal
      echocardiography in patients with severe pulmonary embolism.
AB  - Transthoracic echocardiography generally provides only indirect signs of
      pulmonary embolism. In contrast, with transesophageal echocardiography the
      thromboembolus itself can be visualized in the central parts of the pulmonary
      artery. The aims of our study were to evaluate, first, the incidence of central
      pulmonary artery thromboemboli in patients with severe pulmonary embolism, and
      second, the accuracy of the echocardiographic diagnosis. Our study group
      comprised 60 patients with proved severe pulmonary embolism. All patients were
      examined by transthoracic and transesophageal echocardiography. The
      echocardiographic findings concerning the absence or presence of central
      pulmonary artery thromboemboli were compared with the results of different
      reference methods. Central pulmonary thromboemboli were found in 35 patients
      (58.3%) by echocardiography. Two types of thrombus were differentiated. Type A is
      a long, highly mobile thrombus, and type B is an immobile wall-adherent thrombus.
      In comparison with the reference methods, we determined a sensitivity of 96.7%
      and a specificity of 88% for the echocardiographic detection of central pulmonary
      artery thromboemboli in patients with severe pulmonary embolism. Transesophageal
      echocardiography seems to be a useful method for the diagnosis of severe
      pulmonary embolism. In our series, central pulmonary artery thromboemboli were
      present in more than half of the patients. In these cases, transesophageal
      echocardiography can clarify the diagnosis within a few minutes without further
      invasive diagnostic procedures.

PMID- 1389222
TI  - Transthoracic echocardiography documents prompt resolution of right atrial
      thrombus after thrombolytic therapy.
AB  - Right atrial thrombi represent pulmonary emboli in transit, and they may be fatal
      in patients treated conservatively with anticoagulation. This case provides an
      opportunity to review echocardiographic findings and management decisions in this
      disease entity. As the literature now favors thrombolytic therapy in suitable
      patients, we present a case in which transthoracic echocardiography provided
      rapid assessment of the outcome of this form of therapy.

PMID- 1389223
TI  - Acquired coronary-to-left ventricle fistula: evidence by myocardial contrast
      echocardiography.
AB  - The case report subject is a patient with an old anteroseptal myocardial
      infarction and postinfarction angina who developed, over the years, a small left
      coronary-to-left ventricle fistula. The first coronary angiogram, performed 4
      months after the infarction, was negative for coronary fistula. The diagnosis was
      made 3 years later, at repeat cardiac catheterization with myocardial contrast
      echocardiography. Left and right coronary injections of 0.2 cc of sonicated 5%
      human albumin microbubbles generated a bright cloud of contrast entering the left
      ventricular cavity at the level of the distal third of the interventricular
      septum. Conversely, cineangiography failed to show on-line the fistulous
      communication that was evident only after careful cineangiographic reviewing.
      This case demonstrates the high efficacy of myocardial contrast echocardiography
      in identifying very small coronary fistulae.

PMID- 1389224
TI  - Blood cyst of the mitral valve: detection by transthoracic and transesophageal
      echocardiography.
AB  - Two-dimensional transthoracic and transesophageal echocardiography have become
      important modalities in the evaluation of the mechanism of symptomatic mitral
      regurgitation. We report the use of echocardiography in the detection of an
      unusual cause of mitral regurgitation, that of multiple large blood cysts
      involving the posterior leaflet of the mitral valve.

PMID- 1389226
TI  - Distribution of transforming growth factor beta in a two-week-old human embryo.
AB  - Using immunohistochemical methods we have investigated the presence of
      transforming growth factors beta 1, beta 2 and beta 1 precursor in a two-week-old
      bilaminar human embryo. TGF-beta 1 precursor was seen in both the epiblast and
      the hypoblast. In contrast to the widespread localization of TGF-beta 1 precursor
      in the embryo proper, antibodies to the mature TGF-beta 1 peptide localized
      preferentially to the hypoblast with only weak staining in the epiblast. Staining
      with antibodies to TGF-beta 2 was generally weak in both the epiblast and
      hypoblast layers of the embryo proper. These results show that TGF-beta 1 and
      beta 2 peptides are detectable as early as the second week of human development.

PMID- 1389225
TI  - Regulation of expression of transforming growth factor-beta 2 by transforming
      growth factor-beta isoforms is dependent upon cell type.
AB  - The effect of three different isoforms of transforming growth factor-beta (TGF
      beta) on the expression of TGF-beta 2 mRNA was studied in several continuous
      tumor cell lines. As previously reported for the mouse fibroblast cell line AKR
      2B, the expression of TGF-beta 2 mRNA transcripts of 5.4, 4.7, 3.7 and 3.0 kb was
      decreased after a 24 hr treatment with 5 ng/ml of TGF-beta 1, TGF-beta 2 or TGF
      beta 3. In A549, HBL-100 and BSC-1 epithelial cell lines, five distinct TGF-beta
      2 mRNA transcripts of 5.8, 5.1, 4.0, 3.8 and 2.8 kb were detected by Northern
      blot analysis. Treatment of these cells with TGF-beta 1, TGF-beta 2 or TGF-beta 3
      for 24 hr resulted in a 2-3 fold increase in the 5.8, 4.0 and 3.8 kb transcripts,
      with little detectable change in abundance of the 5.1 and 2.8 kb transcripts. The
      effect of the TGF-beta proteins was dose (5 ng/ml) and time (3-6 hr) dependent. A
      similar 2-3 fold increase in the level of secreted TGF-beta 2 was observed
      following treatment of A549 cells with TGF-beta 1. Basal level and induced
      expression of TGF-beta 2 mRNA in response to TGF-beta isoforms was decreased in
      the presence of actinomycin D. In all cell lines studied, the expression of the
      2.5 kb TGF-beta 1 mRNA was relatively unchanged or markedly increased in response
      to treatment with TGF-beta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389227
TI  - Molecular cloning of CSF-1 receptor from rat myoblasts. Sequence analysis and
      regulation during myogenesis.
AB  - We have isolated and sequenced a cDNA (mrfms) encoding rat c-fms gene (CSF-1
      receptor) from proliferating L6 alpha 1 myoblasts. The predicted amino acid
      sequence was highly identical with the c-fms protein found in monocytes and
      macrophages (98, 76 and 84% identity from mouse, cat and human c-fms proteins,
      respectively). The mechanisms responsible for the regulation of mrfms gene
      expression during myogenesis were examined. Mrfms products were observed during
      proliferation of L6 alpha 1 myoblasts and were downregulated during
      differentiation. Run-on transcription assays demonstrated that the mrfms gene was
      transcriptionally active only in undifferentiated myoblasts. These findings
      suggested that mrfms levels in L6 alpha 1 myoblasts are controlled by
      transcriptional mechanisms. The half-life of mrfms transcripts was found to be at
      least 5 hr while inhibition of protein synthesis with cycloheximide (CHX)
      decreased this half-life to 30 min without changes in the rate of mrfms gene
      transcription. In addition oncogenic transformation of L6 alpha 1 myoblasts by
      the v-fms induced constitutive upregulation of mrfms mRNAs, and nuclear run-on
      assays demonstrated that mrfms transcription was not growth-factor dependent.
      Furthermore, these findings with others previously published indicate that mrfms
      gene products may play a role in the normal and neoplastic growth of muscular
      cells.

PMID- 1389228
TI  - The expression of PDGF alpha- and beta-receptors in subpopulations of PDGF
      producing cells implicates autocrine stimulatory loops in the control of
      proliferation in cytotrophoblasts that have invaded the maternal endometrium.
AB  - In order to explain the high proliferative potential of human placental
      cytotrophoblasts, we have addressed the potential involvement of platelet-derived
      growth factor (PDGF) ligand and receptors. Although PDGF is usually described as
      a mitogen for cells of mesenchymal origin, we show in this report that extra
      villous term placental cytotrophoblasts express the PDGF alpha- and beta-receptor
      genes, both in vivo and in vitro. In addition, cytotrophoblasts produce
      significant amounts of PDGF-B protein. By immunohistochemical analysis of
      receptor expression, we found that the PDGF alpha-receptors could be detected at
      the cell surface, while the PDGF beta-receptors were only detected
      intracellularly. In addition, double immunostaining analysis showed that the PDGF
      alpha- and beta-receptor molecules are expressed in different subpopulations of
      cytotrophoblasts. The addition of PDGF-AA and PDGF-BB homodimers to
      cytotrophoblast primary cultures induced a significant increase in DNA synthesis.
      We conclude, therefore, that PDGF is a growth factor for placental
      cytotrophoblasts and suggest that the growth of cytotrophoblasts can partly be
      explained by a PDGF autostimulatory loop, limited by the number of receptor
      positive cytotrophoblasts.

PMID- 1389229
TI  - Survival of the myeloid progenitor cell line FDC-P1 is prolonged by interferon
      gamma or interleukin-4.
AB  - Continuous proliferation of the immortalized myeloid progenitor cell line FDC-P1
      depends on stimulation with either interleukin-3 (IL-3) or granulocyte-macrophage
      colony stimulating factor (GM-CSF). Two other cytokines, interferon-gamma (IFN
      gamma) and IL-4, were found to prolong FDC-P1 survival for several days.
      Surviving cells incorporated [3H]thymidine and a minority completed up to 3 cell
      divisions before dying. This transient proliferative response was a direct effect
      of IFN-gamma and IL-4 since these cytokines did not induce production of
      detectable IL-3 or GM-CSF and the response was unaffected by cell concentration.
      IL-6, a constitutive product of FDC-P1 cells whose secretion was increased by IL
      3, GM-CSF and IL-4 but not by IFN-gamma, was not responsible for the
      proliferative response. FDC-P1 lines that constitutively expressed the cell cycle
      associated oncogene myc or the survival-associated oncogene bcl-2 also responded
      only transiently to IFN-gamma or IL-4, indicating that expression of these genes
      did not complement the signals delivered by IFN-gamma or IL-4. By contrast, the
      protein kinase C activator phorbol 12-myristate 13-acetate (PMA) prolonged
      survival of FDC-P1 cells on its own and potentiated the response to IFN-gamma or
      IL-4, although the combination of stimuli did not support long-term growth. It is
      concluded that IFN-gamma and IL-4 trigger only some of the signalling events that
      lead to mitogenesis; these events are complemented by stimulation with PMA but
      additional signals are required for sustained proliferation.

PMID- 1389230
TI  - Effects of epidermal growth factor on calf renal glomerular cells in vitro.
AB  - Epidermal growth factor (EGF) stimulates the mitosis and differentiation of a
      variety of cellular types. It also delays the cell senescence in vitro. Because
      of its multiple functions, the effects of EGF on cells from isolated, explanted
      calf renal glomeruli have been studied. The cell types emerging from glomeruli
      cultured with and without EGF were compared and identified by morphological,
      immunofluorescence and electron microscopy criteria. Two cell types: visceral
      epithelial cells or podocytes (type I) and mesangial cells (type II) emerged from
      glomeruli cultivated without EGF. A third cell type, called type III cells,
      appeared only in the presence of EGF. These cells divided, were mobile and had
      prolonged lifespan in culture. They appeared pavement-like, and acquired
      progressively the morphological features and cytoskeletal components of type I
      cells. They also showed certain characteristics of podocytes in vivo. We suggest
      that type III epithelial-like cells are precursor cells of podocytes, that EGF
      triggers their emergence from glomeruli and their subsequent proliferation and
      differentiation in vitro. EGF also prolongs their lifetime in culture.

PMID- 1389232
TI  - Recovery of end-organ failure during mechanical circulatory support.
AB  - To evaluate organ recovery during mechanical assistance, respiratory, hepatic and
      renal function parameters of 40 patients who underwent bridge-to-transplant
      procedures were reviewed retrospectively. Mechanical circulatory support was
      indicated if the hemodynamic and clinical status deteriorated despite
      pharmacotherapy with catecholamines, vasodilators, and intravenous use of the
      phosphodiesterase inhibitor enoximone. Sequelae of cardiogenic shock such as
      renal, hepatic and respiratory insufficiency were not considered a
      contraindication for mechanical support. The analysis of preimplant data such as
      serum creatinine, liver enzymes and pulmonary gas exchange did not identify any
      predictive indicator of irreversible organ damage. Functional recovery of
      preexisting respiratory, hepatic and renal dysfunction was found in 91%, 90%, and
      85%, respectively. Subsequent transplantation, however, was affected by the
      number of failing organs prior to mechanical support. Of 17 patients with
      isolated organ failure prior to assist, 14 (82%) were transplanted. By contrast,
      9 (75%) of 12 with combined failure of two organs, and only 6 (54%) of 11
      patients with clinical patterns of three failing organ systems received
      transplants. In all patients who underwent successful transplantation,
      transplantability was associated with rapid organ recovery within 10 to 15 days
      after initiating mechanical assistance.

PMID- 1389231
TI  - Terminal differentiation of mouse preadipocyte cells: the mitogenic-adipogenic
      role of growth hormone is mediated by the protein kinase C signalling pathway.
AB  - The role of growth hormone (GH) in the differentiation process of Ob1771 mouse
      preadipocyte cells has been studied under culture conditions that were serum-free
      and hormone-supplemented and which were previously shown to lead to terminal
      differentiation. In the absence of GH, a dramatic decrease in the adipogenic
      activity of the culture medium could be observed, as indicated 12 days after
      confluence by the low levels of glycerol-3-phosphate dehydrogenase activity and
      the sharp reduction of the number of triacylglycerol-containing cells. This
      decrease in adipogenic activity was accompanied by a parallel loss of the
      mitogenic potency of the culture medium. Determination of the half-maximal and
      maximal concentrations of GH required for the restoration of growth and
      differentiation were identical, 0.5 and 2 nM, respectively. Despite the presence
      of insulin-like growth factor-I (IGF-I) to substitute for supraphysiological
      concentrations of insulin and to saturate IGF-I receptor, GH was still required
      to induce terminal differentiation of a maximal number of cells. However, protein
      kinase C activators such as prostaglandin F2 alpha, phorbol esters and
      diacylglycerol were able to mimic GH in promoting a maximal mitogenic-adipogenic
      response, indicating that the ability of GH to induce diacylglycerol production
      (Doglio et al., 1989; Catalioto et al., 1990) plays a prominent role in this
      process. Furthermore, in agreement with the fact that the mitoses which precede
      terminal differentiation of Ob1771 preadipocytes are strictly controlled by cAMP
      and only modulated by protein kinase C, terminal differentiation of Ob1771
      preadipocytes occurred in the absence of GH upon supplementation with high
      concentrations of carbaprostacyclin, added as a cAMP-elevating agent or with 8-Br
      cAMP, added as a cAMP analogue. It is concluded that the control exerted by GH on
      terminal differentiation of mouse preadipocytes corresponds to a modulating
      mitogenic effect mediated through protein kinase C activation and leading to a
      potentiation of the cAMP and IGF-I mitogenic signalling pathways.

PMID- 1389234
TI  - Complications from intra-aortic balloon counterpulsation: a review of 303 cardiac
      surgical patients.
AB  - From January 1980 to January 1990 all patients undergoing cardiac surgery at the
      Royal North Shore Hospital, Sydney, and requiring intra-aortic balloon
      counterpulsation (IABCP) were retrospectively reviewed. A total of 99 patients
      (32.6%) developed complications. Vascular/haemorrhagic complications occurred in
      46 patients (15.2%); 79 patients (26%) required platelet transfusions. We have
      found that only a history of hypertension was predictive of an increased
      incidence of developing vascular complications. Surgical intervention was
      required in 17 patients (5.6%), or 47% of the patients who developed a vascular
      complication. The mortality among patients requiring IABCP was 36.6%. Intra
      aortic balloon pump-related deaths occurred in 6 patients (2%). Use of the intra
      aortic balloon pump can be a life-saving procedure, but it carries a significant
      morbidity and mortality rate. This makes it imperative to temper our indications
      to those patients who demonstrate a need for it.

PMID- 1389233
TI  - Early prediction of septic complications after cardiac surgery by APACHE II
      score.
AB  - In 110 patients admitted to the intensive care unit after cardiac surgery, daily
      monitoring [clinical parameters, cardiac index (CI), left ventricular stroke work
      index (LVSWI) and APACHE II score] was performed in regard to its usefulness in
      the early prediction of septic complications, a major cause of postoperative
      mortality. Septic complications (defined as Elebute sepsis score of > or = 12 on
      > or = 2 days) occurred in 16 patients and were associated with a significantly
      worse prognosis (mortality 69% vs 1%, P < 0.0001) than was seen in patients
      without sepsis. While preoperative APACHE II score values did not differentiate
      between the patients with an uneventful postoperative course and those with
      septic complications, patients who ultimately developed septic complications had
      significantly (P < 0.001) higher scores as early as on the evening of the
      operation day ("day 0"). In addition, in contrast to patients without sepsis,
      whose scores dropped markedly (P < 0.001) between day 0 and day 1, patients with
      septic complications invariably had high scores. Compared to single parameters
      (fever, leucocyte count, CI, LVSWI), the APACHE II score proved to be superior in
      differentiating between patients who developed sepsis and those who did not. A
      score of 19 or more on the 1st postoperative day had a sensitivity of 75%, a
      specificity of 98%, a Youden index of 0.73, a positive predictive value of 86%,
      and a negative predictive value of 96% in regard to prediction of septic
      complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389235
TI  - "Very long" aortic grafts.
AB  - During the past 2 decades, we have been using the so-called "very long"
      (ascending to infrarenal aorta or ascending aorta to common femoral artery)
      bypass grafts in selected patients. Our experience with this method includes
      patients with dissecting as well as arteriosclerotic aneurysms of the descending
      aorta, thoracoabdominal aneurysms, patients in need of aortic surgery with
      previous abdominal aortic surgery, radiation treatment, aortic thrombosis, and
      complex aortic coarctation in the adult. The technique proved to be relatively
      easy to perform, was well tolerated by most patients and replaced more
      complicated and higher risk "conventional" operations. The advantages and
      shortcomings of the method as well as long range clinical observations are
      presented.

PMID- 1389236
TI  - Ruptured congenital aneurysm of the sinus of Valsalva: surgical technique and
      long-term follow-up.
AB  - Congenital ruptured aneurysm of the sinus of Valsalva is a rare anomaly usually
      causing decrease of cardiac performance. Eight patients with a ruptured
      congenital aneurysm of the sinus of Valsalva were operated upon at the University
      Hospital Zurich between 1970 and 1991. There were four female and four male
      patients aged from 15 to 48 years (mean, 36 years). Three patients were
      asymptomatic and five symptomatic. Associated congenital cardiac defects were
      found in six patients. Surgical techniques consisted of direct suture in seven
      patients and closure with a Dacron patch in one. A secondary Dacron patch closure
      was performed on the second postoperative day in a patient with suture
      insufficiency after direct closure. Associated operations were closure of
      ventricular septal defect in two patients, aortic valve replacement in two,
      aortic valve reconstruction in one and aortic valve commissurotomy in one
      patient. There were no operative deaths. The mean follow-up was 9 years, range 7
      months to 17 years. There were two late deaths due to endocarditis and recurrent
      cerebral embolisation. An operation for a ruptured aneurysm of the sinus of
      Valsalva has a low operative risk, but patients remain prone to development of
      late valvular complications.

PMID- 1389237
TI  - Pulmonary venous obstruction following correction for total anomalous pulmonary
      venous drainage: a challenge.
AB  - Pulmonary venous obstruction after surgical correction of total anomalous
      pulmonary venous drainage (TAPVD) is a serious condition. Pulmonary venous
      obstruction can be the result of a primary developmental error or is due to post
      operative anastomotic stricture and is usually manifest within 6 months of
      surgery. Prompt restudy is indicated and if a stricture is present, urgent
      surgical relief is indicated. However, the results are often disappointing with a
      high early mortality and a significant chance of restenosis.

PMID- 1389238
TI  - Bilateral single lung transplantation. Complications and results in 14 patients.
AB  - Between November 1989 and April 1991, 14 bilateral single lung transplantations
      (BSLT) were performed at our institution using the technique we have described
      without omentoplasty and rarely cardiopulmonary bypass. The indications included
      emphysema (8), cystic fibrosis (3), infected fibrosis (1), alveolar
      microlithiasis (1) and lymphocytic interstitial pneumonitis (1). Maximum mean
      pulmonary artery pressure was 53 mmHg and minimal right ventricular ejection
      fraction was 15%. Two patients experienced bronchial complications: 1 complete
      left bronchial dehiscence, 1 late partial stenosis which required a temporary
      insertion of a stent. One patient had a posterior dehiscence which healed
      spontaneously. Five patients died postoperatively (3 of infection, 1 after a
      volume mismatch and 1 after a circulating anticoagulant). BSLT is the technique
      of choice for double lung transplantation in adults and heart lung
      transplantation has very few indications in infected end-stage pulmonary disease.
      We hope that modification of our immunosuppressive regimen will decrease
      postoperative mortality.

PMID- 1389239
TI  - Self-expanding metal stent for tracheobronchial strictures.
AB  - To determine the role of expandable metal stent (Wallstent) in treating
      tracheobronchial strictures, 12 patients with recurrent symptoms of airway
      obstruction due to either benign or malignant strictures were studied. The seven
      benign strictures were anastomotic stricture following sleeve resection (2) and
      single lung transplant (1), tracheal amyloidosis (1), idiopathic chondritis (2),
      and post-tracheostomy stricture (1). The five malignant strictures were due to
      recurrent adenoid cystic carcinoma of trachea (1), large-cell carcinoma of lung
      (1), recurrent laryngeal squamous carcinoma (1), squamous carcinoma of the
      trachea (1), and malignant melanoma (1). The placement of stents was performed
      under rigid bronchoscopic guidance with no complications. All patients with
      benign strictures derived subjective and functional improvement with stenting. No
      evidence of restenosis within the stented segment in six of the seven benign
      strictures was found within up to 24 months. Repeated diathermy resection was
      required in the patient with recurrent amyloidosis through the distal end of the
      stent. Among the malignant strictures, symptomatic relief was achieved in four of
      the five patients. One metal stent migrated proximally and was replaced by a
      Montgomery T tube. One patient with relief of stridor died at 4 months due to
      carcinomatosis. Tumour ingrowth through the metal stent remains problematic in
      two patients. However, the incidence of palliative interventions required has
      markedly reduced after stenting.

PMID- 1389240
TI  - Antibiotic prophylaxis in oesophageal surgery.
AB  - A prospective randomised study to assess the efficacy of antibiotic prophylaxis
      in oesophageal surgery was performed, in which 226 consecutive patients (113 male
      and 113 female, age range 24-86 years, mean age of 65 years) were included. The
      study patients were in two groups: group 1, in which the upper alimentary tract
      was opened during surgery, and group 2, in which it was not. The group 1 patients
      (n = 129) were randomised to one of three antibiotic prophylaxis regimes prior to
      surgery. Group A patients (n = 42) were treated with cefuroxime (CFX) 1.5 g at
      induction of anaesthesia and then CFX 750 mg b.i.d. for 4 days. Group B patients
      (n = 46) were treated with CFX 1.5 g and metronidazole (MTR) 1.0 g at induction
      of anaesthesia, then CFX 750 mg b.i.d. and MTR 500 mg qds for 4 days. Group C (n
      = 41) treated with CFX 1.5 g and MTR 1.0 g at the induction of anaesthesia. Group
      2 (n = 97) was divided into two groups, group D (n = 47) treated with CFX 1.5 g
      on induction of anaesthesia alone. Group E (n = 50) treated with CFX 1.5 g on
      induction of anaesthesia then CFX 750 mg bd for 2 days. We found a significantly
      higher incidence of infective complications in subgroup C (43.9%) and subgroup A
      (21.4%) compared to subgroup B (8.6%). This difference was most marked in
      patients undergoing oesophagectomy. We found significantly higher infection rates
      of infective complications in subgroup D (10.6%) as compared to subgroup E (2%).

PMID- 1389241
TI  - Foreign body perforation of the normal oesophagus.
AB  - Over an 11-year period, 12 patients with foreign body perforation of a previously
      normal oesophagus were treated in our institution. The foreign bodies were most
      commonly bones (10 cases), 5 of which were chicken bones; other species were
      pigeon, rabbit, veal, pork and fish (one each); 2 perforations were due to
      swallowed dentures. The mean age was 60 years (range 42-73) and 6 patients were
      female. A degree of psychosocial dysfunction was present in 3 patients. Seven
      patients presented late (> 48 h after ingestion). The commonest presenting
      symptoms were fever and pain (8 patients). Other symptoms included dysphagia (7),
      respiratory distress (3), and late cervical abscess formation (3). The diagnosis
      was established by contrast oesophagography or rigid oesophagoscopy. A third of
      the perforations were cervical, the remainder intrathoracic. All patients were
      treated by surgical drainage with or without primary closure of the perforation.
      There were no operative deaths. Five patients developed postoperative oesophageal
      leaks which required reoperation in 1 patient. All patients were well and
      swallowing normally on discharge from hospital. Follow-up endoscopy or
      oesophagography was carried out in all patients and confirmed the absence of
      oesophageal disorders. Foreign body perforation of the oesophagus is a rare but
      important subentity of oesophageal perforation which responds well to surgical
      treatment.

PMID- 1389243
TI  - Pulmonary autograft failure after aortic root replacement in a patient with
      juvenile rheumatoid arthritis.
AB  - We report a 12-year-old girl suffering from juvenile rheumatoid arthritis with
      severe aortic valve incompetence who died 5 months after an initially successful
      Ross procedure. Pulmonary autograft failure was a result of recurrence of
      aggressive valvulitis.

PMID- 1389242
TI  - Left lower lobe transplantation during a bilateral single lung transplantation
      (pulmonary lobe transplantation).
AB  - An isolated left lower lobe was used as a left graft, during a bilateral single
      lung transplantation procedure, in a patient with infected fibrosis. This
      technique is suitable for patients with small lung volume (especially cystic
      fibrosis) or asymmetric retraction.

PMID- 1389244
TI  - Biocompatibility of extracorporeal circulation with autooxygenation.
AB  - Platelet damage, complement activation and neutropenia during cardiopulmonary
      bypass are the result of blood contact with artificial surfaces, mainly in the
      oxygenator. To evaluate biocompatibility of this kind of bypass we compared two
      techniques of extracorporeal circulation in 40 patients undergoing elective
      coronary bypass operations. In 20, a standard technique with a bubble oxygenator
      was used (group 1), and in the remaining 20 patients with autooxygenation, the
      patients' own lungs were included in the perfusion circuit (group 2). Several
      blood samples were taken before, during and after perfusion to estimate the
      corrected platelet numbers and pulmonary leucocyte sequestration in all patients,
      and additionally in 6 patients from each group, complement C3a and C5a
      anaphylatoxins were measured (radioimmunoassay). At the end of cardiopulmonary
      bypass, the decline of platelet number corrected to haematocrit platelet number
      in group 1 was significantly higher than in group 2 (P less than 0.01). There was
      a significant increase in circulating white blood cells when compared to pre
      bypass time in both groups (P less than 0.05). However, comparison of differences
      between leucocyte counts in the blood of the patients' right and left atria
      showed enhanced leucocyte sequestration in group 1, 1.46 +/- 0.5 x 10(3)/mm3 vs
      only 0.34 +/- 0.2 x 10(3)/mm3 in group 2. The C3a rose progressively during
      extracorporeal circulation: in group 1 from 268 +/- 46 ng/l to 521 +/- 65 ng/l,
      and in group 2 from 244 +/- 46 ng/l to 418 +/- 34 ng/l (P less than 0.05). No
      characteristic changes in C5a activation were observed in either group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1389245
TI  - The relevance of the microbiological flora of the upper alimentary tract to
      postoperative infection in major oesophageal surgery.
AB  - A prospective study to investigate the source of pathogenic organisms responsible
      for infective complications of patients undergoing major oesophageal surgery was
      undertaken in 138 consecutive patients (38 female and 100 male) with obstructive
      lesions of the oesophagus, aged 24 to 86 years (mean 67 years). In all patients,
      the upper alimentary tract (UAT) was opened as part of the surgical procedure and
      20.3% had pathogens present in their sputum before surgery. On direct culture of
      the contents of stomach or oesophagus at operation, 61% showed pathogenic
      organisms. Twenty-five patients suffered from 28 infections, predominantly
      pleuropulmonary infection (n = 19) but also wound sepsis (n = 8) and generalised
      infection (n = 1). Pathogenic organisms could not be cultured from the
      tracheobronchial tree immediately postoperatively. There was no correlation
      between preoperative sputum microbiology and postoperative infection. There was,
      however, a definite correlation (66% of cases) between pathogens of UAT content
      collected at operation and those responsible for postoperative infection. We
      conclude that it is relevant and important to regularly obtain samples of UAT
      content at operation to plan antibiotic regimes.

PMID- 1389246
TI  - Surgical treatment of acute purulent mediastinitis.
AB  - During the last 15 years we have treated 147 patients with acute purulent
      mediastinitis (APM). According to the aetiology of the disease, 2 major groups
      were defined. The first group included the cases of oesophageal origin--112
      patients (dilatation--38 patients, foreign body extraction--29 patients, lye
      injuries--11 patients, oesophagoscopy--8 patients, sharp foreign body--6
      patients). The second group consisted of patients with mediastinitis of non
      oesophageal origin--35 patients (tracheo-bronchial disease--21 patients, tooth
      infection--8 patients, cervical infection). Symptoms of the mediastinal infection
      were typical; nevertheless, early diagnosis (within first 12 h) was obtained in
      only 43.5% of cases. Therapy for all patients included general stabilisation,
      broad spectrum antibiotics and immunotherapy. In 86 patients, mediastinal
      drainage was performed with additional suture of the oesophageal wall or
      plication with a gastric or diaphragmatic patch in 9 cases. Oesophagectomy and
      delayed colon transplant was the method used in 61 patients. Mortality included
      21 patients (14.3%). The cause was broncho-pneumonia in 9 patients, endotoxic
      shock in 7 and renal failure in 3 patients.

PMID- 1389247
TI  - Acute thrombosis of prosthetic valves: a multivariate analysis of the risk
      factors for a lifethreatening event.
AB  - In 3231 prosthetic valves implanted between January 1975 and November 1990, we
      observed 61 cases of prosthetic obstruction of biological origin with clinical
      and laboratory findings of severe functional impairment which required surgery as
      emergency treatment. The hospital mortality was 19.67% (12/61). The obstruction
      was due to a primary thrombosis in all 5 bioprostheses which were not
      anticoagulated and in 11/56 (19.64%) mechanical prostheses of which 3 were not
      anticoagulated and 4 were not properly anticoagulated. The obstruction was due to
      fibrous tissue overgrowth in the other 45 mechanical prostheses (80.35%) with
      secondary thrombosis in 34 cases (60.71%) and no thrombosis in 11 (19.64%);
      71.11% of these prostheses were adequately anticoagulated. Of the 61 obstructed
      prostheses, 53 were mitral and 8 were aortic. No tricuspid obstruction was
      observed. A statistical assessment by multiple correspondence, cluster and chi
      square analysis was performed in two groups of patients with different models of
      mechanical mitral prostheses. The 5-year actuarial incidence of obstruction was
      6.08%. Significant risk factors were: tilting disc prostheses, prostheses without
      pyrocarbon coating, large prostheses, tilting disc prostheses with a small
      orifice posteriorly oriented, atrial fibrillation, enlarged left atrium, time
      from implant greater than 4 years, age between 40 and 50 years. In our opinion,
      prosthetic obstruction may be referred to a primary thrombosis only in cases
      where it may be prevented by adequate anticoagulation. In most cases, the
      obstruction is produced by periprosthetic fibroblastic proliferation which may
      develop in spite of adequate anticoagulation in both groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1389248
TI  - Effect of aspirin on intimal proliferation and tissue cholesterol in long-term
      experimental bypass grafts.
AB  - A single daily dose of aspirin (ASA) reduces the incidence of early graft
      thrombosis after coronary bypass operations. Recent data indicate that aspirin
      may not prevent intimal proliferation and cholesterol uptake in experimental
      bypass grafts which suggests that aspirin may not improve long-term graft
      patency. To further clarify the effects of aspirin on intimal proliferation and
      cholesterol metabolism, we performed femoral interposition vein grafts in 12 dogs
      receiving a 2% cholesterol diet. Six controls (CON) received the diet alone while
      the remaining animals received the diet with 160 mg aspirin daily before and for
      9 months following operation. A segment of each graft was removed at 3 months for
      measurement of intimal thickness and tissue cholesterol. The entire graft was
      then harvested at 9 months. Intimal thickness increased rapidly during the first
      3 months. A slow and progressive increase in intimal thickness was observed
      between 3 and 9 months. There was, however, no difference in intimal thickness
      between the two groups. Tissue cholesterol increased similarly in both groups.
      Rapid cholesterol uptake occurred within the first 3 months and then decreased
      between 3 and 9 months. CONCLUSIONS: (1) ASA failed to reduce intimal
      proliferation and cholesterol uptake in experimental bypass grafts suggesting
      that ASA may not prevent late graft failure, (2) Accelerated intimal
      proliferation and cholesterol uptake occurred within the first 3 months
      emphasizing the importance of developing and instituting anti-proliferative
      therapy immediately after aortocoronary bypass.

PMID- 1389249
TI  - Surgery for bullous disease of the lung.
AB  - Between July 1986 and December 1990, 22 patients underwent 23 operative
      procedures for bullous disease at Harefield Hospital. Their ages ranged from 21
      to 71 years (mean 49.8 years). There were 18 males and 4 females. All patients
      were operated upon for symptoms of exertional dyspnoea. Four patients belonged to
      functional class IV, 11 to class III and 3 to class II. In 80% of patients,
      computed tomography was performed as part of the preoperative assessment. The
      bullae were dealt with in 13 patients on the right side, in 7 on the left and in
      2 bilaterally. Six patients were treated by a modified Monaldi procedure and 17
      by bullectomy. There was no operative mortality. Mean hospital stay was 14.8
      days. Two patients required a second operative procedure during their hospital
      stay for persistent air leak and pneumothorax. One of these had a Monaldi
      procedure in the first instance but underwent bullectomy later. All patients
      improved symptomatically, 10 patients moving up two grades and 12, one grade.
      Mean FEV1, FVC and MVV were significantly improved postoperatively, but there
      were no significant changes in RV or TLC. A graduated exercise test was performed
      in 4 patients. Improvements were seen in ventilation and oxygen consumption at
      anaerobic threshold and maximum exercise. Surgery for bullous disease improves
      symptoms by reducing airway obstruction and increasing ventilatory capacity on
      exercise.

PMID- 1389250
TI  - Acute traumatic isthmic aortic rupture. Long-term results in 49 patients.
AB  - Forty-nine patients who sustained acute traumatic rupture of the aorta at the
      level of the isthmus were treated in our hospital between 1976 and 1990. Four
      patients died before surgery and 45 patients were operated upon using a pump
      oxygenator partial bypass in all but 2 cases (1 clamp and sew and 1 shunt). The
      tear was circumferential in 33 and partial in 12 cases. Direct suture was used in
      the 12 partial and in 21 of the circumferential tears. A dacron tube was used in
      12 patients. Hospital mortality was 3 resulting from brain damage, prolonged
      shock before surgery and necrosis of the colon 4 weeks after operation. No
      paraplegia was observed. There were 2 cases of neurological disturbance (2 spinal
      cord dysfunction 5 and 8 days, respectively, after surgery). These complications
      were transient. Among the 42 survivors, 1 was lost to follow-up. The clinical
      aortic status of the remaining 41 was excellent. Aortic reconstitution as
      assessed by digital aortic angiography was excellent in the 33 cases examined
      with 2 exceptions (graft stenosis, false aneurysm). Our experience and review of
      a large series indicate: the use of a partial bypass with pump oxygenator
      decreases the probability of medullary ischemia, but the risk of spinal cord
      ischemia is not eliminated. When intra-abdominal lesions are life-threatening,
      laparotomy must preceed thoracotomy. Clinical results assessed in long-term
      survivors are excellent, especially after direct repair.

PMID- 1389252
TI  - A study of the stability of orientation in the CarboMedics bileaflet heart valve
      prosthesis.
AB  - A total of 25 CarboMedics bileaflet prostheses was studied in the immediate
      postoperative period and at 1 week, 1 month and 3 months after surgery. No
      evidence of rotation was found on visual comparison of valve orientation and
      there were no significant differences between successive studies for the distance
      between the septum and either the anterior (P = 0.92) or posterior leaflet (P =
      1.00) of valves in the mitral position. The possibility of spontaneous rotation
      is a potential drawback not only of the CarboMedics prosthesis, but also of
      designs currently being developed. This study suggests that major rotation does
      not occur commonly.

PMID- 1389251
TI  - Histological evaluation of the inferior epigastric artery in patients with known
      atherosclerosis.
AB  - Comparative histological studies have been performed on the various arterial
      conduits available for myocardial revascularization including the inferior
      epigastric artery which has recently become the focus of intense investigation.
      In this study, 10 patients with known risk factors for atherosclerotic disease
      had their inferior epigastric artery harvested and the entire specimen examined
      for the microscopical presence of atherosclerosis or its precursors.
      Histopathological findings that have been shown to be theoretically protective
      against the progression of atherosclerosis were observed. These include the
      paucity of fenestrae in the internal elastic lamina, no medical calcification,
      the absence of foam cells and the absence of intimal smooth muscle cells. No
      specimen had atherosclerotic disease and only 3 specimens showed changes
      consistent with minimal intimal hyperplasia. Morphometric analysis of the 3
      diseased specimens revealed only minimal luminal narrowing. These findings
      suggest that the inferior epigastric artery may not be prone to atherosclerosis.
      Thus, the inferior epigastric artery appears to be a safe myocardial conduit and
      long-term patency can be anticipated.

PMID- 1389253
TI  - The place for bilobectomy in bronchogenic carcinoma.
AB  - From 1978 to 1988, 148 bilobectomies (21 upper and middle and 127 lower and
      middle) were performed for bronchogenic carcinoma. A conservative procedure was
      mandatory in 29 patients in whom a pneumonectomy was not functionally feasible
      while bilobectomy was deliberately performed in 119 patients with near normal
      lung function. Overall mortality was 6% compared to 4% and 3%, respectively,
      following pneumonectomies and lobectomies. Preoperative functional status did not
      significantly influence mortality. The complication rate was 55%. The incidence
      of bronchopleural fistula electively observed after lower and middle lobe
      resection was significantly higher (11%) compared to 4% after pneumonectomy and
      1.4% after lobectomy (P less than 0.01). The overall 5-year survival was 43% and
      was similar to that observed at comparable TNM stage after other pulmonary
      resections. Residual right pulmonary function demonstrated by perfusion isotopic
      scan was 24% +/- 10 in 21 long-term survivors. These results indicate that
      bilobectomy can reasonably be considered in patients requiring more than a
      lobectomy but in whom lung conservation is mandatory despite a significant
      increase in morbidity. The risk appears justifiable regarding late survival
      results and functional benefit of the remaining right lobe.

PMID- 1389254
TI  - Severe tricuspid regurgitation following blunt chest trauma: indication for
      emergency surgery.
AB  - A 24-year-old man with polytrauma and severe posttraumatic tricuspid
      regurgitation due to rupture of all three papillary muscles was subjected to
      emergency operation 3 days after a car accident. At operation, all three
      papillary muscles of the tricuspid valve were reinserted. Severe tricuspid
      regurgitation after blunt chest trauma is an indication for emergency surgical
      treatment, and can be performed with a low operative risk.

PMID- 1389255
TI  - Distal exsanguination in aortic aneurysm surgery.

PMID- 1389257
TI  - An immunocytochemical analysis of rapidly progressive atherosclerosis in human
      vein grafts.
AB  - Aortocoronary vein grafts are known to develop atherosclerotic plaques usually
      superimposed on intimal hyperplasia. The cellular characteristics of these
      lesions have been studied with immune cytochemical techniques and compared with
      those in native coronary arteries. Fifteen stenosed grafts showed concentric
      intimal hyperplasia characterized by massive proliferation of smooth muscle cells
      (HHF-35+). The subendothelial layer contained numerous T lymphocytes (UCHL-1+, MT
      1+) and to a lesser extent macrophages (HAM-56+). Eleven grafts had superimposed
      atherosclerotic plaques characterized by atheroma but otherwise showing the same
      cellular constituents. The atherosclerotic plaques in the venous grafts resembled
      those in the coronary arteries, the main difference being the occurrence of
      multiple atheromas (up to 4 in a single section), the high number of T
      lymphocytes and macrophages related to these sites and the presence of atheromas
      bordering directly onto the luminal surface. It thus appears that the development
      of atherosclerotic plaques in vein grafts is accompanied by a similar immune
      inflammatory reaction as in native coronary atherosclerosis, presumably in a more
      aggravated form. The latter phenomenon could relate to the more enhanced and
      rapidly progressive nature of vein graft atherosclerosis.

PMID- 1389256
TI  - Normothermic arrest with continuous hyperkalaemic blood: initial experience.
AB  - The requirement for hypothermia in myocardial protection has recently been
      questioned. Between October 1990 and May 1991, diastolic arrest was achieved
      using continuous perfusion with normothermic, hyperkalaemic blood in 257
      consecutive patients undergoing cardiac surgery. The mean age was 59.8 +/- 9.3
      years (range 28-84 years). Coronary artery surgery was performed in 210 patients,
      valve replacements in 18, combined procedures in 22, and 7 patients had
      miscellaneous procedures. Eleven patients (4.3%) had undergone previous cardiac
      surgery, and 65 (25.3%) required urgent or emergency operations. Hyperkalaemic
      blood (7-20 mmol/l) was delivered antegradely in 190 (72.8%) patients (mean
      aortic root pressure 60-80 mmHg), retrogradely in 62 (25.3%) patients (mean
      coronary sinus pressure less than 40 mmHg), and by a combined route in 5 (1.9%).
      Sinus rhythm returned immediately after removal of the aortic clamp in 235
      (91.4%) patients. Weaning from bypass was achieved without circulatory support in
      207 (82.5%) patients. Of 233 patients undergoing non-emergency coronary artery
      surgery, single valve or combined procedures, 11 died, giving an operative
      mortality of 4.7%. Of 155 patients with good left ventricular function requiring
      coronary artery surgery, 3 (1.9%) died. The in-hospital mortality for the group
      as a whole was 7.3%. Sixteen (6.2%) patients sustained perioperative myocardial
      infarctions; of these 6 died. We conclude that continuous, normothermic,
      hyperkalaemic arrest is a simple and safe method of myocardial protection. It may
      avoid the damage associated with hypothermia, ischaemia and reperfusion.

PMID- 1389259
TI  - Improvement of severely reduced left ventricular function after surgical
      revascularization in patients with preoperative myocardial infarction.
AB  - In recent years, two pathophysiological conditions--stunned and hibernating
      myocardium--have been described showing how function may be depressed in
      myocardium that remains viable. The aims of the present study were postoperative
      assessment of LV function at rest and during exercise after CABG in patients with
      established previous myocardial infarction and impaired preoperative LV function
      and evaluation of preliminary experience with positron emission tomography (PET)
      in the preoperative identification of reversible ischaemic myocardium and its
      predictivity in postoperative functional improvement. We studied 23 patients with
      preoperative LV function under 45%. Echocardiography and complete heart catheter
      were performed pre- and postoperatively. PET was performed in all patients
      preoperatively. In 21 patients with patent grafts, CABG significantly improved
      systolic and diastolic function during exercise and at rest. EF improved from 34%
      +/- 14% to 52% +/- 11% at rest and from 31% +/- 14% to 58% +/- 13% during
      exercise (P less than 0.01). Time constant of diastolic relaxation was
      significantly reduced after revascularization. In 2 patients with pathological
      findings on postoperative coronarangiography, EF remained unchanged. Both global
      and regional contractility improved following surgery. Regional analysis
      indicated that improved EF at rest occurred in regions developing ischaemia
      during exercise before CABG and in regions showing typical mismatch in 82Rubidium
      2-fluoro-2-desoxyglucose suggesting the presence of hibernating
      myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389258
TI  - Is the internal mammary artery an acceptable graft in the elderly patients with
      left main coronary artery disease?
AB  - Age over 70 years and critical stenosis of the left main coronary artery trunk
      are two situations in which the use of the internal mammary artery has been
      questioned. Because the coexistence of these two conditions is increasingly seen,
      we reviewed our experience with 53 patients 70 years of age or older that
      underwent myocardial revascularization for left main disease. In 17 patients, the
      left anterior descending coronary artery was grafted with the left internal
      mammary artery whereas the 36 remaining patients were exclusively revascularized
      by means of saphenous vein conduits. There was no significant difference in
      postoperative mortality or morbidity between the two patient groups. We conclude
      that elderly patients with left main disease should be offered the benefits of a
      mammary artery graft provided they are hemodynamically stable.

PMID- 1389260
TI  - Early results of cryopreserved pulmonary allografts as aortic valve substitute.
AB  - Excellent clinical results with pulmonary autografts and experimental evidence
      that the pulmonary valve can withstand the higher stress in the systemic
      circulation led us to use the cryopreserved pulmonary allograft for aortic valve
      replacement. From September 1988 to March 1991, 45 consecutive patients (59.9 +/-
      12.0 years, 25 men and 20 women) received a cryopreserved pulmonary allograft in
      the aortic position from our hospital based valve bank. All allografts were
      inserted freehand in the subcoronary position. There were 3 in-hospital deaths
      (7%) and 1 patient had severe valvular incompetence immediately postoperatively
      requiring reoperation after 4 weeks. Forty-one patients were followed at 3-6
      month interval for 14.7 +/- 7.8 months (3-28 months) and valve performance was
      assessed routinely by means of color flow Doppler echocardiography: 34 patients
      (83%) had no or trivial aortic valve regurgitation. Valvular incompetence class
      II was present in 2 patients (5%) whereas 3 (7%) demonstrated class II-III.
      Severe aortic regurgitation (class III-IV) could be detected in 2 patients (5%).
      Both had to undergo reoperation 4 months and 15 months, respectively,
      postoperatively. Macroscopic and histological evaluation of the explanted valves
      demonstrated absence of significant degeneration. We assume that a mismatch in
      size between allograft and aortic annulus could have lead to dilatation of the
      allograft valve ring and consequently to valvular incompetence. Pulmonary
      cryopreserved allografts achieve acceptable short-term results which can be
      improved if initial technical problems can be avoided.

PMID- 1389261
TI  - Lung transplantation with bronchial revascularisation. Surgical anatomy,
      operative technique and early results.
AB  - Ischaemic anastomotic complications are an important cause of mortality and
      morbidity after lung transplantation. Anatomical studies have demonstrated that
      the pattern of bronchial arterial supply is relatively constant and therefore
      amenable to attempts at revascularisation. From May 1990, 10 patients who had a
      double lung transplantation (tracheal anastomosis) and 1 patient who had a right
      lung transplantation underwent concomitant bronchial revascularisation. There
      were two early and one late deaths. There were no anastomotic complications.
      Regular endoscopic examination showed satisfactory healing in all patients. Early
      angiography showed patent grafts in 7 of 9 patients. At a mean follow-up of 11
      months (range 6-17 months) 8 patients are well and leading a normal life. This
      report describes the anatomical basis, technical aspects and early results of a
      promising operative procedure in the field of lung transplantation.

PMID- 1389262
TI  - Classification of airway anastomotic healing.
AB  - Airway complications remain a major problem after lung transplantation. There is
      no standardised method of assessment of airway healing. We propose a
      classification of airway healing based on the anastomotic appearances at
      endoscopy 15 days postoperatively. The system appears to correlate well with the
      subsequent development of anastomotic sequelae and can be used to assess the
      effectiveness of therapeutic modalities designed to reduce airway complications.

PMID- 1389263
TI  - Squamous cell carcinoma of the lung: prognostic factors affecting the long-term
      outcome after surgical resection.
AB  - From 1976 to 1989, 638 patients with squamous cell carcinoma were operated on.
      Reliable information concerning survival could be obtained in 540 of these cases
      via follow-up examinations. All tumors were retrospectively classified according
      to the TNM system of the fourth edition of UICC classification. The average
      survival time after potentially curative operation was 7.32 years in patients
      with stage I tumors, the 5-year survival rate was 55.3%. The corresponding values
      were 2.42 years and 29.1% respectively in patients with stage II tumors, compared
      to 1.22 years and 12.0% respectively in those with stage III a tumors. The
      differences between tumor stages are statistically significant. Analyzing the
      influence of the T and N factors on the prognosis following potentially curative
      surgery, the classification in the various tumor stages was largely verified.
      Stage III a is inhomogeneous in terms of prognosis. T and N factors showed
      prognostic value in this group. In the group with T3 tumors there was a
      significant difference in the mean survival times, independently of the lymph
      node status, when the patients were divided into those with T3 tumors close to
      the main carina (16 months) and those who had infiltrated adjacent structures
      (7.5 months). When differentiating the N1 location, a significant difference was
      found between the group of patients with T2 tumors and true lymph node metastases
      and the group with T2 and direct tumor infiltration of the lymph node (mean
      survival time 27.5 vs 42.3 months).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389264
TI  - Antiheart antibodies following open heart surgery: incidence and correlation with
      postpericardiotomy syndrome.
AB  - One-dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis of
      myocardial proteins followed by Western blotting is a sensitive method for the
      detection of antiheart antibodies after cardiac transplantation. In a previous
      study we found that the majority of patients made antiheart antibodies after
      cardiac transplantation. It is possible that these antibodies were formed in
      response to cardiac damage caused during the surgical procedure rather than being
      specific to the transplantation situation. In this study we have evaluated the
      role of open cardiac surgery in the formation of antiheart antibodies for the
      first 9 months of the postoperative period using the Western blotting technique
      and correlated that with the development of post-pericardiotomy syndrome. Only
      25% (9/36) of patients showed any increase in the pre-existing level of antiheart
      antibodies or developed antiheart antibodies with new reactivities. None of the
      patients in the study developed manifestations specific for post-pericardiotomy
      syndrome during the period of follow-up. The results support the contention that
      the high incidence of antiheart antibodies formed after cardiac transplantation
      is due to a humoral immune response to the presence of alloantigens on the
      grafted heart rather than as a result of the surgical procedure itself.

PMID- 1389265
TI  - Partial brachiocephalic perfusion under hypothermic cardiopulmonary bypass. An
      experimental study.
AB  - We studied electrophysiological, oxygen metabolic, and histological variables in
      dogs to establish the reliability and safety of partial brachiocephalic perfusion
      (PBP) under hypothermic cardiopulmonary bypass (CPB) at 23 degrees-25 degrees C.
      Sixteen mongrel dogs were divided into two groups. Six (control group) underwent
      typical hypothermic CPB for 90 min, and 10 (PBP group) underwent PBP under
      hypothermic CPB for 90 min. During core cooling on the CPB, a progressive
      reduction in voltage and slowing of frequency of the electroencephalogram (EEG)
      was observed. At around 23 degrees C nasopharyngeal temperature the tracing
      became almost flat and remained so throughout the hypothermic CPB or the PBP
      under hypothermic CPB. Consistent recovery of the EEG was, however, observed
      during the period of rewarming on the CPB, and the voltage and frequency of the
      EEG recovered to control levels on weaning off CPB at 36 degrees C in both
      groups. In the PBP group, the cerebral arteriovenous oxygen (AVO2) difference was
      12.4 +/- 4.0 vol% before beginning the CPB, and it was 5.6 +/- 2.7, 5.7 +/- 3.1,
      5.4 +/- 3.3, and 4.9 +/- 2.9 vol% at 10, 30, 60, and 90 min respectively after
      commencement of the PBP under hypothermic CPB. The cerebral AVO2 difference
      measured 10 min after commencement of the PBP was significantly less than that in
      the control group (P less than 0.05), but otherwise there were no significant
      differences between cerebral AVO2 differences in the two groups. Concentration of
      serum creatine kinase-BB (CK-BB) gradually increased in proportion to the
      duration of CPB in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389267
TI  - Oesophageal erosion of an Angelchik prosthesis: surgical management using
      fundoplication.
AB  - Complications following insertion of the Angelchik prosthesis are becoming
      increasingly recognised. We report a 35-year-old patient with both mediastinal
      migration and intraluminal oesophageal erosion of a prosthesis. Successful
      management included transthoracic removal combined with a modified onlay
      fundoplication over the oesophageal defect to prevent gastro-oesophageal reflux.

PMID- 1389266
TI  - Conversion of lusoric artery into right subclavian artery in one-stage neonatal
      repair of aortic arch anomalies and intracardiac defects.
AB  - In 2 patients, a lusoric artery was compressing the mediastinal structures during
      a one-stage repair of type B aortic arch interruption and ventricular septal
      defect. In order to prevent the long-term complications of sacrifice of the
      subclavian artery, the lusoric artery was not simply divided but converted into a
      regular right subclavian artery by re-implantation of the abberant vessel at the
      origin of the right carotid artery during the one-stage repair. At follow up,
      both patients have normal right radial arterial pulsations. In one patient,
      angiography was repeated and confirmed a well functioning right subclavian
      artery. Conversion of a lusoric artery into a right subclavian artery during one
      stage repair of aortic arch anomalies and intracardiac defects is not only
      feasible but also indicated to preserve subclavian artery function and to prevent
      compression of the mediastinal structures by a vascular ring.

PMID- 1389268
TI  - New developments in clinical testing of medical devices for Europe 1992.
AB  - The unification of Europe is associated with the introduction of many new
      regulations aiming at, for example, standardization and quality control. Several
      of these generally normative regulations are pertinent to clinical investigations
      of medical devices, such as heart valves, pacemakers and cardiac assist devices.
      Relevant documents dealing with these regulations are the "Guidance for good
      clinical practice for trials on medicinal products in the European Community," a
      standard already passed by the European Parliament, and CEN (Comite Europeen de
      Normalisation) document TC258 dealing with "Clinical investigations of medical
      devices". The latter standard is in discussion among member states of the
      European Community. In this present survey the most important issues dealt with
      in these documents will be summarized with emphasis on the aspects relevant to
      clinical investigations of medical devices.

PMID- 1389269
TI  - Mechanical circulatory support in the 1990s.
AB  - The current experience in bridging patients to weaning (more than 965 implants)
      and to transplantation (more than 544 implants) has shown the feasibility of
      mechanical circulatory support in patients with major cardiac dysfunction, who
      are unresponsive to optimal medical management. The complications are mostly
      related to the patient's initial condition at the time of implantation. The
      rehabilitation of the patient is related to both the extent of recovery from
      organ dysfunction and the type of device. This analysis proposes some new
      orientations for research. Firstly, in clinical research, definition of precise
      indices of the patient condition, not exclusively related to the haemodynamic
      situation, should allow better patient and device selection. Secondly, in
      technological research, precise definition of the actual clinical objectives
      should help in the development of various systems: for resuscitation, for
      bridging purposes and for long-term or permanent implantation.

PMID- 1389270
TI  - In vitro pulsatile flow hemodynamics of five mechanical aortic heart valve
      prostheses.
AB  - In vitro measurements of velocity, turbulent shear stress, effective orifice area
      (EOA), and regurgitant fraction were performed on five new-generation low-profile
      mechanical aortic heart valve designs under pulsatile flow conditions. These
      were: Medtronic-Hall tilting disc, St. Jude Medical bileaflet, Bjork-Shiley
      Monostrut tilting disc, Omni-Carbon tilting disc, and Duromedics bileaflet. In
      general, bileaflet valves have larger EOAs than the tilting disc design,
      especially in the larger sizes, due to the larger opening angles and lack of
      obstructive struts. The regurgitant fractions range from 8% for 21-mm valves to
      13% for the 29-mm sizes. This increase was largely due to an increase in leakage
      volume as opposed to closing volume. Furthermore, the leakage volumes increased
      as the mean aortic pressures increased. The tilting disc valves generally have
      better regurgitant characteristics compared to the bileaflet valve designs, due
      to lower leakage volumes and to the smaller opening angle of the occluder
      providing a more rapid closure of the valve. The velocity and shear stress
      measurements showed that none of the current valve designs are ideal: all designs
      create areas of stasis and/or regions of low-velocity reverse flow and regions of
      elevated turbulent shear stresses capable of causing sublethal and/or lethal
      damage to the formed elements of blood. It is therefore unlikely that these valve
      designs will eliminate the problems of hemolysis, thrombosis, and thromboembolic
      complications.

PMID- 1389271
TI  - The Intact porcine bioprosthesis: early world-wide clinical experience and
      analysis of a single institution's experience.
AB  - The Intact porcine bioprosthesis is a new-generation valve fixed under stress
      free conditions and subjected to a mineralization-inhibiting treatment. The valve
      is undergoing multi-centre prospective clinical evaluation sponsored by
      Medtronic, Inc., with 19 centres participating world wide. Since April 1986, 1465
      valves have been implanted in the aortic position (AVR, n = 965), mitral position
      (MVR, n = 438), or both (n = 62), and followed up to 5 years. The data recorded
      at our participating centre, with 115 valves implanted (AVR n = 93, MVR n = 22)
      closely match the overall event and death rates in the prospective study. Early
      mortality in the overall study is 5.6% in AVR and 6.6% in MVR; 3-year actuarial
      survival rates are 88.5% in AVR and 85.6% in MVR; structural valve-failure-free
      rates at 3 years are 99.8% in AVR and 98.5% in MVR; 3-year freedom from valve
      related reoperation is 97.3% in AVR and 95.8% in MVR. The preferential use of
      bioprosthetic valves in patients aged 70 years and older with no other indication
      for anticoagulant treatment entails the not infrequent occurrence of
      patient/prosthesis mismatch in AVR. Hence, when implanting bioprostheses in old
      patients, the acceptance of some mismatch has to be weighed against the freedom
      from anticoagulation treatment and the expected long-term freedom from structural
      valve failure. Further long-term follow-up will be required to demonstrate the
      greater durability expected from the stress-free fixation and the anti
      mineralization treatment.

PMID- 1389272
TI  - Mitral valve repair into the 1990s.
AB  - Mitral valvuloplasty has become an increasingly accepted alternative to valve
      replacement, although the strong learning curve attached to the procedure has
      deterred many surgeons from adopting it. Since it was developed in the late 1960s
      by Carpentier, comprehensive valvuloplasty has undergone modifications and
      additions dictated by the experiences thus acquired, which have contributed to
      make it a more reproducible and predictable procedure. Mitral valve disease,
      especially that of rheumatic origin, has a multifactorial pathogenesis, as all
      the components of the valve apparatus are usually involved. Consequently,
      valvuloplasty requires a combination of multiple techniques, each one directed at
      correcting each affected component. The excellent median-term results observed by
      some of the more experienced groups have contributed to change the indications
      for surgery, and patients are being referred earlier and in a lower functional
      class. Hence, in mitral valve prolapse surgery is currently offered to
      asymptomatic patients with significant regurgitation, before dysfunction of the
      myocardium and dilatation of the cardiac chambers occur. Valve repair has been
      possible and successful in virtually all patients with this pathological
      condition. On the other hand, surgeons are becoming more aggressive towards
      ischaemic mitral regurgitation of mild or moderate severity. More recently,
      valvuloplasty has also been performed in some patients with infective
      endocarditis, with good results. By contrast, the long-term results in rheumatic
      disease appear favourable, especially in children and young patients with acute
      carditis. Nevertheless, they have still been proven better than those of valve
      replacement in these population groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389273
TI  - Importance of the mitral apparatus for left ventricular function: an experimental
      approach.
AB  - In an experimental study of 31 anesthetized dogs the importance of the mitral
      apparatus for the left ventricular function was investigated. During
      extracorporeal circulation bileaflet mitral valve prostheses were implanted
      preserving the mitral subvalvular apparatus. Flexible wires were slung around the
      chordae tendineae and exteriorized through the left ventricular wall to cut the
      chordae by electrocautery from the outside when the heart was beating again.
      External and internal left ventricular dimensions were measured by
      sonomicrometry, left ventricular stroke volume by electromagnetic flowmeters
      around the ascending aorta, left ventricular end-diastolic volume by dye dilution
      technique, and left ventricular pressure by catheter tip manometers. Different
      preload levels were achieved by volume loading with blood transfusion before and
      after cutting the chordae tendineae. When the chordae had been divided peak
      systolic left ventricular pressure did not change. Heart rate only increased at
      the lowest left ventricular end-diastolic pressures of 3-4 mmHg, but remained
      unchanged at higher preload levels. Cardiac output decreased significantly up to 
      9% at left ventricular end-diastolic pressures of 5-10 mmHg, while left
      ventricular dp/dtmax showed a consistent reduction of up to -15% at any preload
      level. Significant reductions were also seen in systolic shortening in the left
      ventricular major axis (by external measurements -27%, by internal recording 
      43%). Left ventricular end-diastolic dimensions increased in the major axis by
      +2% when recorded externally, by +10% when measured internally. Systolic and
      diastolic changes in the minor axis were not consistent and different in the
      external and internal recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389274
TI  - Echo Doppler principles, techniques and applications for the cardiac surgeon.
AB  - Doppler echocardiography is increasingly used not only to identify disease in
      native heart valves, but also to assess the function of prosthetic valves. The
      purpose of this paper is to provide a summary of the principles of Doppler
      echocardiography for the cardiac surgeon which will lead to a discussion of
      assessment of prosthetic valve function. Solid cardiac structure imaging is first
      discussed in both one-dimensional (M-mode) and two-dimensional (B-mode)
      modalities. Measurements of blood cell velocities by conventional spectral
      Doppler echocardiography are then discussed, leading to two-dimensional flow
      imaging by color Doppler flow mapping. Assessment of prosthetic valve function is
      divided into two sections: normal prosthetic valve function and prosthetic valve
      dysfunction. Subtopics within each of these divisions are discussed in the
      context of conventional and color Doppler ultrasonography.

PMID- 1389276
TI  - Valve prosthesis hemodynamics and the problem of high transprosthetic pressure
      gradients.
AB  - Recent studies suggest that all prosthetic valves are at least mildly stenotic
      and may cause relatively high pressure gradients despite normal prosthesis
      function; such gradients could be due to a mismatch between prosthesis effective
      orifice area and patient's body size. In order to address this problem more
      directly, we derived, using a physiologic pulse duplicator system, the
      theoretical relations between transprosthetic pressure gradients and prosthesis
      effective orifice areas indexed for body surface area, assuming a normal resting
      cardiac index of 3.0 l/min m-2 and 10-50% increases in stroke volume such as may
      occur during maximal upright exercise. These exponential relations show that a
      small decrease in indexed effective orifice area produces a large increase in
      pressure gradient, and that the indexed effective orifice area should ideally be
      not less than 0.9-1.0 cm2/m2 for aortic prostheses and 1.3-1.5 cm2/m2 for mitral
      prostheses in order to minimize postoperative gradients. Thus, high postoperative
      gradients do not necessarily indicate intrinsic prosthesis dysfunction but may
      also be due to patient prosthesis mismatch. Intrinsic prosthetic performance is
      best assessed by comparing in vivo calculated effective orifice areas to in vitro
      measurements for same type and size of prosthesis. Patient prosthesis mismatch
      can be avoided by calculating before operation the projected indexed effective
      orifice area of the prosthesis being implanted.

PMID- 1389275
TI  - Anatomy of aortic heart valve leaflets: the influence of glutaraldehyde fixation
      on function.
AB  - The basic function of the aortic valve is reviewed from an engineering
      perspective. Critical examination of the leaflet morphology can yield insights
      into how the leaflets function and transmit load to the aortic wall. From an
      understanding of both the structure and the function it is possible to estimate
      the impact of stent mounting and glutaraldehyde fixation. It is shown from simple
      engineering considerations that the major stresses are in the circumferential
      direction and that the radial components must be very small. Similarly, the
      largest strains are radial to facilitate the formation of a large coaptation
      area, while the circumferential strains are explained by the extension to the
      crimped collagen fibres. Glutaraldehyde fixation can greatly modify the mechanics
      of the leaflets but this can be minimized by fixation with no pressure
      differential across the closed valve. Zero-pressure-fixed leaflets are much
      softer and extensible than those from valves fixed under even low back-pressure
      (2-4 mmHg). This difference translates into a mode of valve function that more
      closely approximates that of the native aortic valve.

PMID- 1389277
TI  - The stentless bioprosthesis: surgical challenges and implications for long-term
      durability.
AB  - An attempt is made to analyse the factors which are expected to influence
      clinical results following implantation of a stentless porcine bioprosthesis.
      Long experience with implantation of allograft aortic valves provides a
      meaningful basis for comparison with a glutaraldehyde-fixed device. Morphological
      differences between the two valves involve the aortic wall and muscle shelf, and
      differences in valve preparation include the strength and stiffness of the aorta
      and the extensibility of the valve leaflets. As a result of these differences,
      sizing of the porcine valve is expected to be more critical than the allograft
      valve and the porcine valve is also expected to be more obstructive. Methods for
      reducing the obstructive element include the use of a composite aortic valve, a
      porcine pulmonary valve, or a valve in which the aorta is glutaraldehyde-fixed
      under pressure while the leaflets are pressure-free. The techniques available for
      implantation, namely freehand insertion, total root replacement and mini-root
      replacement, are examined.

PMID- 1389278
TI  - Aortic root replacement: modifications of technique with improvements in
      technology.
AB  - Potential morbidity remains substantial in aortic root replacement. The tissues
      are often fragile, contributing to the risk of haemorrhage and postoperative
      complications. In the past surgery has been directed towards minimising
      haemorrhage by wraparound techniques and the right atrial fistula method of
      Cabrol. However, recent use of aortic homografts, collagen-impregnated grafts and
      tissue glues have reduced bleeding and simplified operative technique. Profound
      hypothermia and total circulatory arrest allows aneurysm resection to extend into
      the aortic arch. Between 1986 and 1991 25 aortic root replacements were carried
      out at the Oxford Heart Centre in 21- to 76-year-olds, 13 for aorto-annular
      ectasia (4 due to Marfan's syndrome), 7 for aortic dissection (2 Marfan's
      syndrome) and 2 for complications of previous aortic valve replacement. Three
      patients had homograft root replacement for aortic root endocarditis. We
      implanted 14 Medtronic composite grafts, 1 St Jude conduit and 7 collagen-coated
      Dacron grafts (Hemashield, Meadox) into which a Starr-Edwards valve was sewn, as
      well as 3 homografts. One patient with a massive chronic dissection following
      previous aortic valve replacement required an interposition graft to the coronary
      ostia. In the others, the coronary ostia were mobilised from the native aorta and
      directly implanted into the conduit. In dissections a ring of pericardium or
      GoreTex was used to buttress the coronary anastomoses. Six patients also required
      coronary artery grafting. Native aorta was excised and not wrapped around the
      conduit. Coagulation defects were corrected aggressively with platelets, fresh
      frozen plasma and cryoprecipitate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389279
TI  - The first step to understanding valve failure: an overview of pathology.
AB  - The most frequent valve-related complications are thromboembolic problems
      (including anticoagulant-related hemorrhage), infective endocarditis,
      paravalvular leak, intrinsic degradative dysfunction, and extrinsic interference
      with function, including tissue overgrowth. Tissue overgrowth, endocarditis, and
      paravalvular leak are largely prosthesis-independent. Thrombosis, the major cause
      of mechanical valve dysfunction, is infrequent with bioprostheses; in contrast,
      the overwhelming cause of bioprosthetic valve failure is primary tissue
      degeneration.

PMID- 1389280
TI  - Techniques of valvular reoperation.
AB  - Valve replacement is simply the exchange of one disease for another. Degeneration
      of bioprostheses and thrombotic obstruction of mechanical valves, other forms of
      prosthetic dysfunction and prosthetic valve endocarditis are the main
      complications leading to reoperation. Repeat valve surgery is more complex than
      primary surgery and therefore carries a higher mortality and morbidity, even in
      the hands of experienced surgeons. Several technical details of valve replacement
      have contributed to the improved results obtained by some surgical groups.
      Difficulties start with the opening of the sternum, especially in cases where the
      pericardium was not closed during the initial operation. Cardiopulmonary bypass
      may be instituted in the usual fashion or may be done by cannulation of the
      femoral or iliac vessels. The heart need not be completely liberated from the
      adhesions. Access to the aortic root is usually not difficult, but the left
      atrium may be less accessible. Removal of the prosthesis also requires precise
      technique, for disruption of the annulus or damage to other valves or
      neighbouring structures may occur. Finally, the choice of valve substitute and
      technique of implantation must be tailored to the patient's characteristics and
      the type of pathology. One of the most important causes of morbidity and
      mortality after reoperation is perioperative and postoperative bleeding,
      resulting from the extensive dissection and from the coagulation disorders,
      including anticoagulation treatment. Pharmacological manipulation has recently
      contributed to reduce the severity of this complication. The results of repeat
      valve surgery have improved markedly and have now reached values which
      approximate those of primary valve replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389281
TI  - Reoperation and the centrifugal pump?
AB  - Postperfusion syndrome is still a problem in long cardiac operations using
      extracorporeal circulation (ECC). To evaluate whether or not centrifugal blood
      pumping during open heart surgery is beneficial, a randomized, prospective study
      was undertaken of 50 consecutive patients undergoing elective coronary artery
      bypass grafting. The patients were divided into two groups of 25 each. In group 1
      a centrifugal pump (Biomedicus) was used as arterial blood pump, while in group 2
      a roller pump (Stockert) was used. The two groups did not differ significantly
      and the number of variables during surgery was kept low (identical perfusion set,
      two surgeons, minimal cardiotomy suction). The parameters studied included the
      cellular elements of the blood and components indicating their functional
      integrity, such as PMN-elastase, plasma hemoglobin, beta-thromboglobulin, and
      thrombin-antithrombin III complex and D-dimer as representatives for activated
      coagulation and secondary fibrinolysis. Blood and urine samples were taken every
      15 min during ECC, on arrival in the intensive care unit, and 1, 3, 6, 12, and 24
      h thereafter. No difference between the groups was found in regard to bypass
      time, ECC flow and volume, fluid balance, and clinical outcome. Significant
      differences in favor of group 1 were found in plasma hemoglobin (P less than
      0.05), beta-thromboglobulin (P less than 0.01), D-dimer (P less than 0.05), and
      platelet counts (P less than 0.5). These differences were clearly ECC-time
      dependent and became statistically significant after 90 min bypass. We conclude
      that roller pumps still can be safely used for standard cardiac
      procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389282
TI  - The Medtronic-Hall valve: a design in 1977 to improve the results of valve
      replacement.
AB  - The prototype Medtronic-Hall valve was developed from improvements to the
      Lillehei-Kaster and Bjork-Shiley valves. The housing was constructed of a single
      piece of titanium and the disc was composed of pyrolytic carbon; both materials
      had shown no structural breakdown in previous clinical use. The valve was tested
      with pulse simulator and electromagnetic flow meter studies and yielded a high
      effective orifice area. Results in 110 patients were significantly better with
      the Medtronic-Hall valve than with either of the previous valves. In the 21-mm
      aortic valve the peak-peak gradient was 12 mmHg; it was 9.2 mmHg in the 23-mm,
      3.8 mmHg in the 25-mm, and 2.5 mmHg in the 27-mm. Studies found 5% of forward
      flow regurgitation in the aortic position and more than desired regurgitation
      through the mitral valve. After the opening angle of the mitral valve was reduced
      to 70 degrees, regurgitation reached an acceptable level and the improved
      hemodynamics resulted in lower transvalvular gradients than in previous
      mechanical valves. Some patients are naturally more prone to thromboembolism
      regardless of valve type or anticoagulant therapy; thus the human factor plays a
      large role in a valve's success. More randomized studies are needed for accurate
      valve comparison, in addition to investigations of sewing ring factors.
      Nevertheless, the Medtronic-Hall valve has been used successfully for 15 years
      and has exhibited no housing fractures.

PMID- 1389283
TI  - Review of the global experience with the Medtronic-Hall valve.
AB  - The Medtronic-Hall cardiac valvular prosthesis has been available for insertion
      since 1977. This report reviews the English language literature concerning that
      valve published during the last 14 years. The review is focused on three modes of
      assessment. First, experience with valve implantation techniques and their
      results has demonstrated that with careful attention to education of the
      implanting cardiac surgeon and increasing experience in the clinical use of the
      prosthesis, the incidence of occluder impingements has steadily fallen to 0.2% of
      total valve implantations in the United States in 1989. Secondly, hemodynamic
      assessment of the prosthesis with both invasive catheterization and Doppler
      echocardiography has demonstrated rest and exercise transvalve gradients and
      functional valve areas that are as good or better than those in other mechanical
      cardiac valvular prostheses. Finally, review of the long-term follow-up reports
      of the Medtronic-Hall prosthesis has demonstrated an acceptably low incidence of
      late valve-related complications and their consequences.

PMID- 1389285
TI  - Clinical experience with the zero-pressure-fixed Medtronic Intact bioprosthetic
      valve.
AB  - The Medtronic Intact porcine valve bioprosthesis was inserted in 219 patients
      between 1983 and 1990. Mean patient age was 52 years and mean follow up 33.3
      months. There was only one example of structural valve degeneration at 25 months,
      giving an actuarial freedom of 99% at 6 years. Reoperation was performed in 7
      patients. Freedom from reoperation was 93% at 6 years, from infective
      endocarditis 96%, from thrombo-embolism 91% and from valve-related complications
      86%. Doppler echocardiography revealed non-significant incompetence in 8
      instances and mild leaflet thickening of 5 valves. Valve gradients and areas were
      unchanged between two Doppler studies 2 years apart of valves in the mitral
      position, and were reduced in valves in the aortic position from 17 +/- 5.2 mmHg
      to 13 +/- 2.8 mmHg (P = 0.02). These medium-term results are considered very
      encouraging. The theoretical considerations underlying the use of zero-pressure
      glutaraldehyde fixation, which is the technique used for the Intact valve, are
      detailed elsewhere in this issue [1]. The Intact valve is treated with toluidine
      blue as a calcium-retarding agent and is mounted on a Dacron-covered acetyl
      copolymer (Celcon) stent with flexible posts. The normal profile of the porcine
      aortic valve is maintained.

PMID- 1389286
TI  - Heart valve bioprosthesis durability: a challenge to the new generation of
      porcine valves.
AB  - Long-term experience with first generation porcine valve xenografts enabled
      identification of the major limitations to their durability: (1) prosthetic
      ventricular mismatch due to the high profile of the stent in patients with mitral
      stenosis and a small left ventricle; (2) high-pressure fixation with loss of
      natural collagen crimping in the fibrosa, and wash-out of proteoglycans in the
      spongiosa; (3) xenograft tissue autolysis, due to the long interval between
      animal slaughter and aortic valve removal fixation; (4) muscle shelf in the right
      coronary cusp, which created a gradient and could undergo accelerated
      calcification and/or spontaneous perforation with time; (5) a flexible
      polypropylene stent, which could creep or even fracture with consequent inward
      bending of the stent; (6) progressive time-related dystrophic calcification; (7)
      host fibrous tissue ingrowth. An awareness of these limitations stimulated
      technical modifications, which frequently brought about distinct improvements:
      (1) the reduction of the stent profile eliminated the problem of mismatch, but
      resulted in a higher tendency towards cusp prolapse and earlier commissural
      tearing; (2) natural collagen waviness, proteoglycans and cusp extensibility were
      preserved by employing low or even zero pressure during the fixation process; (3)
      earlier valve fixation enabled preservation of cell integrity; (4) a new orifice
      for small valves was designed by replacing the right muscular cusp, thus
      achieving less gradient and avoiding muscle-shelf-related complications; (5)
      polypropylene was replaced by Delrin as stent material; (6) calcium-retarding
      agents like T6 and toluidine blue were applied during commercial processing and
      storage in order to mitigate tissue mineralization.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1389287
TI  - Heart valve bioprostheses: antimineralization.
AB  - Clinical and experimental studies indicate that calcification of bioprosthetic
      valves depends on host, implant, and biomechanical factors. The earliest mineral
      deposits in both clinical and experimental bioprosthetic tissue are localize to
      transplanted connective tissue cells; collagen involvement occurs later. Passive
      calcium entry occurs unimpeded in cells modified by aldehyde cross-linking, but
      the mechanisms for calcium removal are dysfunctional; calcium influx contributes
      to apatite formation by reacting with compartmentalized, bound phosphorus.
      Specific strategies for prevention of bioprosthetic tissue mineralization involve
      modification of either valve preparation details or the local implant
      environment. Efficacy, mechanisms and safety must be demonstrated for any
      antimineralization strategy.

PMID- 1389284
TI  - Original expectations of the Hancock valve and 20 years of clinical reality.
AB  - The standard (glutaraldehyde-preserved) Hancock porcine bioprosthesis was
      introduced into clinical practice in order to provide surgeons with a cardiac
      valve substitute which would be nonthrombogenic and therefore would not require
      anticoagulation, and would be durable, anatomically suitable, and noiseless. In
      the present report we have reviewed our long-term experience with Hancock porcine
      valve recipients in order to verify the original expectations of this
      bioprosthesis have been met.

PMID- 1389288
TI  - Computer modelling of bioprosthetic heart valves.
AB  - The underlying assumptions and principles of a computer-based model for tissue
      heart valves are described. The model is used to relate observations of leaflet
      morphology to the requirements of proper valve function. Stress is the
      fundamental mechanical factor that limits the longevity of bioprosthetic heart
      valves--the higher the stress levels in the leaflets, the shorter will be the
      time over which the leaflets can maintain satisfactory structural integrity.
      Direct measurement of stress is impractical with real heart valves, but the
      calculation of stress and the study of its interdependence on other key
      parameters of tissue valve design is a good alternative. The methodology of
      computer modelling of heart valves is discussed and the technique is illustrated
      with some examples. Models of pericardial valves, the aortic allograft and
      porcine bioprostheses are compared.

PMID- 1389289
TI  - [The Madrid school of neurology in the old Hospital General de Madrid].

PMID- 1389290
TI  - [Metachromatic leukodystrophy: an exceptional cause of dementia in the adult].
AB  - Hereditary metabolic diseases are an exceptional cause of neurological disorders
      in adults. Metachromatic leukodystrophy is a hereditary alteration of the
      metabolism of myelin which may be manifested in adults as intellectual
      deterioration. A case of metachromatic leukodystrophy presented in adulthood is
      presented with cognitive deterioration and behavioral alterations as the only
      clinical manifestation. The patient was a 28 year old male studied for dementia
      of one year of evolution. Computerized tomography and cranial magnetic resonance
      demonstrated diffuse and symmetric involvement of the periventricular white
      matter. The visual evoked potentials were involved while the brain stem auditory
      potentials were normal. Study of the speed of nerve conductions was compatible
      with demyelinating neuropathy. The diagnosis of metachromatic leukodystrophy was
      confirmed by enzyme study revealing very diminished levels of aryl-sulfatase A.
      Although it is exceptional the adult form of metachromatic leukodystrophy should
      be included in the differential diagnosis of dementia. Computerized tomography
      and cranial magnetic resonance together with neurophysiologic studies are the
      principle procedures orienting diagnosis to this disease.

PMID- 1389291
TI  - [Polymicrogyria and ulegyria. Diagnosis by magnetic resonance].
AB  - Three patients who had had epilepsy since the second decade of life were studied
      with cranial magnetic resonance (MR). Two patients had no antecedents of interest
      during pregnancy and the perinatal period and neurological examination was
      normal. The third patient had had dystocia and presented left hemiparesia since
      then, with normal intellectual development. None of the cases had any family
      history of neurological disease. Cranial magnetic resonance was performed in the
      three patients demonstrating polymicrogyria in two and ulegyria in the other, in
      addition to other lesions. The first patient presented an unilateral area of
      polymicrogyria related with a porencephalic cyst in the distal territory of the
      right sylvian artery and ipsilateral heterotopia of periventricular location. The
      second patient presented bilateral periventricular heterotopia, partial agenesis
      of the corpus callosum and an enlarged cisterna magna in addition to bilateral
      frontal-occipital polymicrogyria. Finally, ulegyria was observed in the third
      patient in the edges and neighboring regions of a right rolandic porencephalic
      cyst, as well as an enlarged cisterna magna.

PMID- 1389292
TI  - [Chorea and primary antiphospholipid syndrome: effective treatment].

PMID- 1389294
TI  - [Muscular pseudohypertrophy caused by chronic radiculopathy].

PMID- 1389293
TI  - [Agranulocytosis caused by ticlopidine].

PMID- 1389295
TI  - [The food of Antarctic penguins].

PMID- 1389296
TI  - [When should intracranial aneurysms be operated on?].

PMID- 1389297
TI  - [Motor fluctuations in Parkinson disease: risk factors].
AB  - We studied the histories of 173 patients with Parkinson's disease (1985-1987)
      chronically treated with levodopa + dopa decarboxylase inhibitor. Ninety four
      patients had daily motor fluctuations and 79 showed stable motor response. The
      most significant differences between fluctuating and stable patients were given
      by age at disease onset and duration of levodopa therapy. Patient with disease
      onset before 60 had a greater risk (p less than 0.001) of developing
      fluctuations. Delaying the initiation of levodopa treatment was not associated
      with a smaller incidence of fluctuations.

PMID- 1389298
TI  - [Minimal-intensity carpal tunnel syndrome. Diagnostic sensitivity of various
      electrophysiological tests].
AB  - The most sensitive tests for the electrophysiological diagnosis of the carpal
      tunnel syndrome (CTS) were studied in asymptomatic hands contralateral to those
      objectively involved. The presence of dromic potential of "double peak" by
      stimulation of fingers 1 and 4, with detection of equidistant points of Median
      and Radial and Median and Cubital respectively, in the wrist, was the test
      demonstrating the earliest and most constant alterations. The detection of
      alterations with a frequency of subclinical character is of interest in the
      quantitative evaluation of CTS and in the recognition of the wide spectrum of the
      intensity of involvement of this compression syndrome.

PMID- 1389299
TI  - [Delayed-action calcium antagonists and therapy of arterial hypertension].
AB  - Drug treatment of high blood pressure had important improvements is the last few
      decades, that allowed an efficiente control of hypertension, avoiding or
      stabilysing cardiovascular consequences. Non pharmacological management is always
      important; however most hypertensive patients need also drug treatment that is
      unavoiable in severe and in most cases of moderate hypertension. Borderline
      hypertension involves difficult decisions. Quantitative diagnosis of high blood
      pressure has been based on casual measurement. Non invasive ambulatory blood
      pressure measurement gives access to much more valures over the whole day and
      night periods, and has been an important tool for clinical research. However it
      implicates a correct assessment of the device's accuracy and calibration, and
      also a correct statistical treatment of the huge range of values obtained. Blood
      pressure control over the 24 hours is probably obtained with some long acting
      drugs. So, calcium antagonista are reviewed, exemplofying with slow release
      diltiazem. It has been prescribed twicely a day, and more recently once a day,
      what is considered by some authors quite adequate on the point of view of
      pharmacocinetics and pharmacodynamics. So the benefits depending on patient's
      compliance and the possible obliteration of hypertensive spikes may be important.
      There is perhaps, in the overall, reduction of health care costs, in what
      concerns hypertension.

PMID- 1389300
TI  - Antihypertensive treatment and regression of atherosclerosis.
AB  - Reduction of high blood pressure has an effect on coronary mortality and
      morbidity lower than expected. One of the possible explanations is the different
      anti-atherogenic capacity of anti-hypertensive drugs. Reduction of high blood
      pressure has, by itself, an anti-atherogenic effect, but, for some anti
      hypertensive drugs, there is experimental and clinical evidence of anti
      atherogenic properties. For calcium antagonists experimental data have been
      published reporting reduction of aortic lipidic deposition and decrease of
      arterial proliferation. The INTACT trial has shown that the development of new
      atherosclerotic lesions was delayed by nifedipine. For beta-blockers, in spite of
      the negative effect on atherogenic fractions, the experimental evidence, so far
      collected, suggests a possible anti-atherogenic effect. ACE inhibitors have been
      experimentally studied and its anti-atherogenic effect reported on studies with
      the WHHR rabbit and cynomolgus monkey. The different possible mechanisms for
      these anti-atherogenic properties are analysed. Ketanserine is a serotonin
      antagonist witch anti-atherogenic capacity is under investigation on the PACK
      trial. The results that were published so far seem to confirm that capacity.

PMID- 1389301
TI  - [Doppler echocardiography in the diagnosis of mechanic complications of acute
      myocardial infarction].
AB  - OBJECTIVES: To evaluate the ability of bedside emergency
      Doppler/Echocardiographic (ECOCG/DP) studies in the diagnosis of mechanic
      complications during acute myocardial infarction (AMI). DESIGN: Retrospective
      analysis of 44 fatal AMI cases, studied by ECOCG/DP and with diagnostic
      confirmation by surgery and/or necropsy. SETTING: Patients (pts) with AMI
      admitted to an Intensive Care Unit of a tertiary Hospital (UCIM), Hospital de
      Santa Maria. PATIENTS: 44 fatal AMI cases were analysed (24 men and 20 women;
      mean age +/- SD: 72 +/- 9 years) and were divided in two groups according to
      Killip classification in Group 1 (III/IV): 35 pts and Group 2 (I/II): 9 pts.
      METHODS: ECOCG/DP was performed in a routine basis at admission, using all
      standard views and by subcostal view when in an emergency scenario. RESULTS: In
      20 pts with bad left ventricular function (LVF) (Group 1) at admission, ECOCG/DP
      monitoring showed that death was due to worsening of LVF, which was confirmed by
      necropsy. In the other 15 pts of this group, ECOCG/DP documented the clinical
      diagnosis of cardiac rupture (free wall: 4 pts; papillary muscle: 4 pts;
      interventricular septum: 7 pts) which was confirmed by surgery and/or necropsy.
      In the 9 pts of Group 2, ECOCG/DP disclosed, at admission, good LVF in all. In 5
      pts there was a sudden worsening clinical status, and ECOCG/DP showed a severe
      pericardial effusion with right chambers collapse, highly suggestive of free wall
      rupture also confirmed at necropsy. In the other 4 pts, ECOCG/DP showed
      aggravation of wall motion abnormalities and of LVF without rupture, once again
      in agreement with necropsy. Five clinical cases are presented for illustration of
      this issue. CONCLUSION: In the 44 fatal AMI cases of our study there was complete
      agreement between the ECOCG/DP and necropsy studies. In AMI patients, ECOCG/DP
      monitoring can in a routine basis, evaluate wall motion abnormalities and LVF. In
      an emergency setting ECOCG/DP can diagnose all the mechanic complications with a
      great certainty.

PMID- 1389302
TI  - [Unsustained ventricular tachycardia and accelerated idioventricular rhythm-
      clinical and electrocardiographic features].
AB  - OBJECTIVE: To compare clinical and electrocardiographic characteristics of
      Nonsustained Ventricular Tachycardia (NSVT) and Idioventricular Accelerated
      Rhythm (IVAR). MATERIAL AND METHODS: We studied 155 patients, 113 men and 42
      women, with mean age 54 +/- 14 retrospectively, of these, 108 had NSVT and 47
      IVAR. The arrhythmias were defined as follows: NSVT-more than 3 ventricular
      consecutive beats with an heart rate superior to 110 b/m and lasting less than 30
      s.; IVAR-3 or more ventricular consecutive beats with an heart rate equal or
      superior to 50 and lower than 110 b/m, lasting less than 30 s. We evaluated
      clinical data (symptoms, functional class and anti-arrhythmic therapy),
      electrocardiographic data (rhythm, changes in conduction and repolarization) and
      ventricular function (with ECO, Radionuclide Angiography or Ventriculography). In
      the Holter recording (ECG-H), we analysed the presence of associated ventricular
      arrhythmias, their electrocardiographic characteristics (number of episodes,
      number of beats per episode, previous arrhythmia rate, morfology, regularity) and
      the relations of the arrhythmia with symptoms. RESULTS: Analysis of underlying
      pathology showed in both groups, the importance of coronary artery disease (44.5%
      vs 40%) followed by valvular heart disease (24% vs 27.6%) and cardiomyopathy
      (22.2% vs 17%) respectively to NSVT and IVAR. Only in the NSVT group there were
      patients without cardiac pathology (3.6%). Comparing with one control group of
      our department, this distribution was substantially different (p less than
      0.0001). All IVAR episodes were assympthomatic compared with 90% of NSVT.
      Ventricular premature beats were found in all NSVT patients and in 90% of IVAR
      patients, and were frequent (greater than 10/h) in 79% and 60%, couplets in 84%
      and 53% respectively (ns). The previous rate of the arrhythmia was 85.3 +/- 20
      b/m in NSVT against 68.7 +/- 14 in IVAR (p less than 0.0001). We found left
      ventricular disfunction in 60% of NSVT patients and in 63.7% in IVAR patients,
      being serious in 35% and 39% respectively. The follow-up was of 18.5 months (1
      72) and posterior evolution showed 14.8% and 17% of deaths with no relation to
      the arrhythmia, although in NSVT the number of complexes and episodes were
      related with the ventricular disfunction (p = 0.02 and p = 0.05). CONCLUSION:
      Both arrhythmias appeared in patients with similar clinical and arrhythmic
      setting and identified a population with structural cardiopathy, bad function and
      poor outcome.

PMID- 1389303
TI  - [Transesophageal echocardiography. Experience at the Pulido Valente Hospital (the
      first 50 cases)].
AB  - The use of echocardiography is increasingly important in the evaluation of
      cardiac patients. METHODS: The results of the First fifty examinations of the
      Department of cardiology (Hospital de Pulido Valente). We evaluate the
      contribution of the T-E-E on the therapeutic decisions of these patients.
      RESULTS: The clinical condition for which T-E-E were particularly appropriate
      were: embolism detection, evaluation of Mitral valvular regurgitation and
      prosthetic function, detection of vegetations in patients with suspicion of
      bacterial endocarditis, detection of intracardiac shunts. The examines were
      conclusive in 88% of the patients.

PMID- 1389304
TI  - [Echocardiography-guided temporary implantation of electrode catheters: an
      alternative with reliable results even during prolonged use].
AB  - OBJECTIVE: Two-dimensional echocardiography (2D-ECO) evaluation as an alternative
      guidance technique during temporary pacing wire placement. DESIGN: Prospective
      evaluation of implantation and pacing parameters. SETTING: Admission from the
      Emergency Room and patients studied in the Cardiology Department of the Hospital
      Distrital in Faro. PATIENTS: Twenty patients with indication for temporary
      cardiac pacing during, at least, twelve hours (H). Fluoroscopy equipment
      shouldn't be readily available for implantation. INTERVENTIONS: The mean ages of
      the 20 pts. (14 men and 6 women) were 71.90 +/- 2.12 years. All pts. had a
      temporary pacing lead implantation under 2D-ECO guidance. Indications for cardiac
      pacing were: second or complete atrioventricular block (17 pts.), new onset
      bifascicular bundle branch block during anterior acute myocardial infarction (1
      patient) and sick sinus syndrome (2 pts.). The transvenous route of approach has
      been the right internal jugular in all the cases and venipuncture time accounts
      for the calculation of total implantation time. MEASUREMENTS AND RESULTS:
      Ventricular capture was achieved in all pts., with stable stimulation thresholds.
      The mean implantation time was +/- 9.21 minutes and the mean acute stimulation
      threshold 0.33 +/- 0.20 V and 0.65 +/- 0.35 mA. The mean voltage of the
      intracavitary QRS was 11.15 +/- 2.95 mV and the mean lead resistance was 851.33
      +/- 194.04 Ohms. The mean utilization time of the pacing leads was 95.15 +/-
      87.49 H and the mean stimulation threshold during lead explanation was 0.85 +/-
      0.47 mA. The only complication appearing during our study has been one lead
      dislodgment (5%), 72 h after implantation, placed again with the guidance of 2D
      ECO and used during 216 H without further complications. Subcostal 2D-ECO window
      alone was used in 85% of the pts. but in the remaining (15%), it was insufficient
      and an apical window was needed too. CONCLUSIONS: The 2D-ECO was an efficient
      alternative technique of guidance during temporary lead placement, ensuring
      satisfactory longterm pacing and sensing. Our results indicate that 2D-ECO may be
      the best alternative control for urgent lead implantation whenever fluoroscopic
      facilities are remote or logistically not convenient.

PMID- 1389305
TI  - [Heart failure in the elderly (from diagnosis to therapy)].
AB  - After some considerations about the importance of heart failure on the elderly,
      the medical literature about epidemiologic and necropsy data on etiologic forms
      of heart failure, is reviewed. The importance of the associated pathologies to
      heart failure on the elderly is evaluated in what the diagnosis and treatment of
      this syndrome is concerned. We characterize the physiopathologic types of heart
      failure on the elderly. We refer how important is to recognize the treatable
      forms of heart failure, mainly the aortic valve stenosis.

PMID- 1389306
TI  - [Initial aspects of essential hypertension].

PMID- 1389307
TI  - [Interventricular communication after silent myocardial infarction. Report of a
      case].

PMID- 1389308
TI  - [Clinical significance of hypercholesterolemia in the elderly].
AB  - Hypercholesterolemia is known as a cardiovascular risk factor for the non elderly
      man. But it still remains the controversy about the significance of dislipidemia
      on the aged. The authors discuss the problem and suggest a therapeutic approach
      following the European Consensus Conference Guidelines.

PMID- 1389309
TI  - [Young men's views on health and health promotion].
AB  - The purpose of the research was to describe views on health and health promotion
      of young men. A survey was made of a sample of 150 selected from a group of men
      aged under 30 years whose employment placed them within the scope of the
      government service occupational health scheme. The results presented here are
      derived from a questionnaire that had a response rate of 70%. The results show
      that these men had a broad outlook on matters of health as a whole. An open
      question was used to elicit views on health. Almost all the subjects mentioned
      physical and psychological well-being. The major factor the observation of
      healthy living habits was adequate, properly internalized information. The most
      important motive for healthy living habits was their current well-being. The
      research provides information for the development of health education within the
      scope of the government service occupational health scheme.

PMID- 1389310
TI  - [Job stress and well-being of care providers: development of a standardized
      survey instrument].
AB  - The main aim was to develop a standardized survey instrument for measuring job
      stress and well-being in hospital settings. The actual study group consisted of
      349 workers from medical bed wards, first aid unit wards and bed wards for
      gynecology and obstetrics in a middle-sized hospital in the Helsinki region.
      Based on the factor analysis of separate questions, the following content areas
      were chosen for the job stressor scales: haste at work, problems in interpersonal
      relations at work, problems in occupational collaboration with others, too much
      responsibility, safety and health risks, lack of appreciation, troublesome
      patients, and lack of equipment and resources. Content areas for well-being
      scales and items were general job satisfaction, strain symptoms, perceived mental
      and physical work load. The reference values of the questionnaire and
      reliabilities for the scales were calculated. The application and further
      development of the questionnaire was discussed.

PMID- 1389311
TI  - [Knowledge and skills of newly graduated nurses].
AB  - Nursing education was recently reformed in Finland. By now nurses who have
      graduated from the new programmes have already entered nursing practice. The
      purpose of this study is to describe the following two aspects: 1) How do the
      newly graduated nurses assess their own skills and knowledge on completion of
      their nursing studies and what is their assessment four months later? 2) What
      skills and knowledge did the nurse managers expect the nurses to have and what,
      in fact, did they discover when the new nurses began their work in practice? The
      data were collected by questionnaires, measuring the competencies of professional
      nurse (Clayton 1983) from a sample (N = 30), which consisted of registered nurses
      (response rate was 67%), specialized in medical-surgical nursing, and their nurse
      managers. The nurses had graduated from two different colleges of nursing. Data
      were analysed by the means and differences of the means. On completion of their
      studies the nurses felt that their best skills and knowledge were related to the
      hygienic care of the patient, while their weakest area was in implementing
      specialized care. In their assessment made four months after graduation the
      nurses felt that in terms of the different areas of nursing practice their skills
      and knowledge had improved to some degree. The nurse managers, on the other hand,
      expected the newly graduated nurses to have better skills and knowledge than what
      was actually discovered. Furthermore, the nurse managers were clearly more
      critical in their assessment than the nurses themselves.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1389312
TI  - [Collaborative decision-making by patient and nurse in nursing practice].
AB  - The topic of this study was the collaborative decision-making of patients (n =
      302) and nurses (n = 253) and it is a part of an international research project.
      The data were gathered from the surgical and medical wards of two Finnish
      hospitals by means of a questionnaire. The results showed participation in
      decision-making by patients to be uncommon and the collaborative decision-making
      by patient and nurse together also occurred seldom.

PMID- 1389313
TI  - The Entner-Doudoroff pathway: history, physiology and molecular biology.
AB  - The Entner-Doudoroff pathway is now known to be very widely distributed in
      nature. Biochemical and physiological studies show that the Entner-Doudoroff
      pathway can operate in a linear and catabolic mode, in a 'cyclic' mode, in a
      modified mode involving non-phosphorylated intermediates, or in alternative modes
      involving C1 metabolism and anabolism. Molecular and genetic analyses of the
      Entner-Doudoroff pathway in Zymomonas mobilis, Escherichia coli and Pseudomonas
      aeruginosa have led to an improved understanding of some fundamental aspects of
      metabolic controls. It can be argued that the Entner-Doudoroff pathway is more
      primitive than Embden-Meyerhof-Parnas glycolysis.

PMID- 1389315
TI  - Protein secretion in Pseudomonas aeruginosa.
AB  - The Gram-negative bacterium Pseudomonas aeruginosa secretes many proteins into
      the extracellular medium. At least two distinct secretion pathways can be
      discerned. The majority of the exoproteins are secreted via a two-step mechanism.
      These proteins are first translocated across the inner membrane in a signal
      sequence-dependent fashion. The subsequent translocation across the outer
      membrane requires the products of at least 12 distinct xcp genes. The exact role
      of one of these proteins, the XcpA protein, has been resolved. It is a peptidase
      that is required for the processing of the precursors of four other Xcp proteins,
      thus allowing their assembly into the secretion apparatus. This peptidase is also
      required for the processing of the precursors of type IV pili subunits. Two other
      Xcp proteins, XcpR and XcpS, display extensive homology to proteins involved in
      pili biogenesis, which suggests that the assembly of the secretion apparatus and
      the biogenesis of type IV pili are related processes. The secretion of alkaline
      protease does not require the xcp gene products. This enzyme, which is encoded by
      the aprA gene, is not synthesized in a precursor form with an N-terminal signal
      sequence. Secretion across the two membranes probably takes place in one step at
      adhesion zones that may be constituted by three accessory proteins, designated
      AprD, AprE and AprF. The two secretion pathways found in P. aeruginosa appear to
      have disseminated widely among Gram-negative bacteria.

PMID- 1389314
TI  - Microbial breakdown of halogenated aromatic pesticides and related compounds.
AB  - Considerable progress has been made in the last few years in understanding the
      mechanisms of microbial degradation of halogenated aromatic compounds. Much is
      already known about the degradation mechanisms under aerobic conditions, and
      metabolism under anaerobiosis has lately received increasing attention. The
      removal of the halogen substituent is a key step in degradation of halogenated
      aromatics. This may occur as an initial step via reductive, hydrolytic or
      oxygenolytic mechanisms, or after cleavage of the aromatic ring at a later stage
      of metabolism. In addition to degradation, several biotransformation reactions,
      such as methylation and polymerization, may take place and produce more toxic or
      recalcitrant metabolites. Studies with pure bacterial and fungal cultures have
      given detailed information on the biodegradation pathways of several halogenated
      aromatic compounds. Several of the key enzymes have been purified or studied in
      cell extracts, and there is an increasing understanding of the organization and
      regulation of the genes involved in haloaromatic degradation. This review will
      focus on the biodegradation and biotransformation pathways that have been
      established for halogenated phenols, phenoxyalkanoic acids, benzoic acids,
      benzenes, anilines and structurally related halogenated aromatic pesticides.
      There is a growing interest in developing microbiological methods for clean-up of
      soil and water contaminated with halogenated aromatic compounds.

PMID- 1389316
TI  - Immunoglobulin prophylaxis during intensive treatment of acute lymphoblastic
      leukemia in children.
AB  - 60 children with acute lymphoblastic leukemia were sequentially randomized at the
      time of diagnosis: Immunoglobulin (Endobulin, Immuno) was administered
      intravenously to 30 patients at a dose 100 mg/kg/week during the first 3 months,
      followed by 2 x 200 mg/kg/month immunoglobulin during the 4., 5., 6. months. No
      immunoglobulin was administered to the control patients. We studied the effect of
      immunoglobulin prophylaxis on the number of days with fever, number of cases with
      bacteriologically proved infections, length and frequency of antibiotic therapy.
      Our data confirm the efficacy of immunoglobulin prophylaxis during the intensive
      phase of leukemia therapy in children.

PMID- 1389317
TI  - Smith-Lemli-Opitz syndrome in siblings.
AB  - This paper presents two brothers with incomplete expression of the Smith-Lemli
      Opitz syndrome. A definite diagnosis, made after the birth of the second child,
      could only be reached when the clinical features of both patients were combined.

PMID- 1389318
TI  - Severe hypoglycaemia and cardiovascular autonomic dysfunction in type I diabetic
      children treated with intensified conventional insulin therapy.
AB  - To assess the relationship between severe hypoglycaemias and autonomic
      dysfunction, five cardiovascular tests (resting heart rate, hyperventilatory
      arrhythmia, standing/lying heart rate ratio, orthostatic decrease in blood
      pressure, and increase in blood pressure during sustained handgrip) were
      performed in a 1-yr prospective study of 34 insulin-dependent diabetic children
      treated with intensified conventional insulin therapy (ICIT). There were twelve
      severe episodes in 7 diabetic children, and the remaining 27 patients had no
      severe hypoglycaemia. The hypoglycaemic group had a longer duration of diabetes
      than the nonhypoglycaemic group (5.4 SD 2.5 years vs. 2.8 SD 2.2 years, p less
      than 0.02). The hyperventilatory arrhythmia in the hypoglycaemic group in
      comparison with the nonhypoglycaemic group was significantly decreased (before
      ICIT: 16.1 SD 3/min vs. 24.4 SD 5/min, p less than 0.01; 1 yr thereafter: 17.3 SD
      3/min vs. 26.0 SD 5/min, p less than 0.01). The hypoglycaemic group showed a
      pronounced orthostatic decrease in blood pressure compared to the
      nonhypoglycaemic group (before ICIT: 13.2 SD 4 mmHg vs. 6.0 SD 4 mmHg, p less
      than 0.01; 1 yr thereafter: 12.3 SD 4 mmHg vs. 5.6 SD 4 mmHg, p less than 0.01).
      Three or more abnormal cardiovascular test results were found in patients of the
      hypoglycaemic group who showed abnormal hyperventilatory arrhythmia and abnormal
      orthostatic decrease in blood pressure simultaneously, whereas such a coexistence
      was not found in the nonhypoglycaemic group. These observations may support the
      view that diabetic children and adolescents with autonomic dysfunction are
      susceptible to severe hypoglycaemia during ICIT.

PMID- 1389319
TI  - Sex hormone binding globulin (SHBG) in children with obesity.
AB  - Serum sex hormone binding globulin (SHBG) concentration of children with obesity
      was measured and relationships between SHBG level and body mass index (BMI),
      waist hip ration (WHR), serum insulin, C-peptide, thyroid hormones (thyroxine-
      T4, triiodothyronine--T3/ sexual hormones (testosterone--T, oestradiol--E2) were
      investigated. Significant negative correlations were found between SHBG
      concentration and BMI, serum insulin, C-peptide concentration; significant
      positive concentrations were found between BMI and serum insulin, C-peptide
      concentration. Thyroid hormone and sexual hormones did not associate with SHBG
      levels. These results suggest that insulin hypersecretion has an important role
      in determining the reduction of SHBG production in obesity.

PMID- 1389320
TI  - Determination of hair trace elements in childhood celiac disease and in cystic
      fibrosis.
AB  - Applying proton-induced X-ray emission authors investigated the hair trace
      element contents in 10 children with acute celiac disease after 3 to 6 and 12
      months long gluten-free diet; in 9 children with cystic fibrosis and in a control
      group (6 children) of the same age. There was no difference in Cu, Fe, Ca, Cl
      values between the examined groups. The Zn contents of the hair are significantly
      low in the group with acute celiac disease after a short-term diet and also in
      the group with cystic fibrosis, the data approach the normal range only after a
      year's diet. The significant rise of hair potassium contents is well indicated in
      patients with acute celiac disease and this rise may be due to the destruction of
      cell cuticles. In case of cystic fibrosis there is no significant rise of hair
      potassium value.

PMID- 1389321
TI  - In vitro motility investigations and electron microscopic observations on
      children's upper urinary tract muscle wall.
AB  - This study was performed as a part of a longer research programme on urinary
      tract smooth muscle layer in children. All the children whose samples were
      investigated underwent surgery for urinary tract malformations. Specimens were
      taken from different segments of upper urinary tract during surgical
      intervention. Specimens were investigated by either in vitro motility tests or
      electron microscopy or both of them. Basic patterns of tissue strips were
      recorded after incubation of varying duration and then tested by administering
      neurotransmitter agents like noradrenaline and acetylcholine-bromide.
      Microstructure of samples were examined electron microscopically. Investigations
      were performed in order to find correlation between microarchitecture and
      motility patterns of urinary muscle wall. Factors influencing urinary muscle
      motility, characteristic features of impaired musculature and its possible
      regeneration are discussed too. Microhistological deteriorations inhibit
      spontaneous smooth muscle motility but muscle contractility proved by
      administering noradrenaline and acetylcholine-bromide remained in some extent.
      Taking into consideration that smooth muscle is able to regenerate and rebuild
      close contacts pediatric surgeon and urologist should spare kidney parenchyma as
      far as it is possible.

PMID- 1389322
TI  - "Effects of prostaglandin E2 on the newborn respiratory system".

PMID- 1389323
TI  - Maternal weight gain and birth weight.
AB  - The data of first 1000 non-malformed, mature (greater than or equal to 2500 g)
      singletons of participants in the Hungarian Family Planning Programme were
      evaluated. The mean maternal weight gain during pregnancy was 13 kg which was
      modified by the body weight of women. Maternal weight gain exceeded 13 kg in 54%
      of pregnant women. There was a positive correlation between maternal weight gain
      and birth weight which was calculated as 26.6 g/kg.

PMID- 1389324
TI  - [Feeding problems in severely handicapped children].
AB  - Nineteen patients with severely handicapped children were divided into 3 groups;
      tube-fed patients (group 1, n = 8), oral-fed patients with dysphagia (group 2, n
      = 3) and oral-fed patients (group 3, n = 8). Clinical symptoms, past history,
      cranial CT, EEG, blink reflex and auditory brainstem response were evaluated in
      these patients. All patients of group 1 and 2 could not control head or sit by
      themselves. They needed naso-oral suction. However, nasal airway, intubation and
      tracheostomy were necessary only in group 1 patients. Five out of 8 patients of
      group 3 could control head and sit by themselves. No one needed naso-oral
      suction. CT revealed ventricular dilatation or prominent destructive lesions in
      group 1. However, patients of group 2 and 3 showed the lesions of mild to
      moderate degree. EEGs showed poorly developed background activities or electrical
      status epilepticus in group 1, while they showed relatively well-developed
      background activities with less prominent paroxysmal discharges in group 2 and 3.
      R2 component of blink reflex was absent bilaterally in 90% patients of group 1
      and 2, while unilateral R2 at least was present in group 3. Feeding problems in
      severely handicapped children were affected by combination of cerebrum and
      brainstem involvements. Examination of cranial CT, EEG and blink reflex was
      useful to determine the method of feeding.

PMID- 1389325
TI  - [Speech development test for one-year-old infants: I. Test content].
AB  - A new speech development test was prepared for one-year-old infants. The test
      consists of three parts: test I, II, and III. The overall test originally
      comprised a total of 98 test items (47 for Test I, 32 for Test II and 19 for Test
      III). Test I (for pre-speech language) Section 1 Situation of language i)
      Differentiation of information to be communicated ii) Comprehension of speech
      related situation (Initiation of "signe", and comprehension of objects and events
      by means of speech) Section 2 Development of symbolizing function (Development
      and transformation of ability to handle and manipulate objects) section 3
      Representing the function of language (First utterance, and acquisition of
      meaningful words after first utterance) Test II (for speech comprehension)
      Ability to name concrete objects, and to relate objects to their uses and
      functions; comprehension of words representing spatial concept such as quantity,
      number and dimensions, as well as words representing color or position. Test III
      (for speech expression) Ability to verbalize or name concrete objects, and to
      verbalize the conduct and state of a person. For infants, language is an
      objective to be achieved, while for adults it is the mean of thinking and
      communicating. Despite this difference the scope of this test comprises two major
      aspects common to the language-related experience of infants and of adults:
      pragmatics and vocabulary.

PMID- 1389326
TI  - [Speech development test for one-year-old infants: II. Test statistics].
AB  - The test result of language ability for infants of second year of life was
      examined statistically. In descriptive statistics, average score, standard
      deviation, and proportion of right answers for all test items for each age group
      subjects were included. Then factor analysis was carried out to determine the
      structural characteristics of the test. The analysis revealed that test pertains
      of the following five stages. First two stage of five were overlapped with the
      previously reported result for pre-speech language test for infant within one
      year of life. Then, the stage was determined as follows; (4) Initial language
      acquirement and differentiation of language functions (5) Speech increasing stage
      (increase of spontaneously uttered words and understood words related to persons
      and objects) (6) Differentiation of expressed words (expression of words
      differentiated to suit objects) (7) Understanding of words representing actions
      or conditions (8) Understanding of words representing uses or functions, and
      verbalization of words representing actions or movements In spite of the fact
      that six and seven stage represent the same development level in term of
      chronological age, they were distinctive into those which achieve speech
      understanding earlier (stage 7), and others whose development centers on speech
      expression (stage 6). Then reliability and validity was performed. Reliability:
      (1) As to homogeneity, the reliability coefficients were calculated on the 60
      test items by Spearman-Brown's odd-even method. (2) As to inter-rater
      reliability, Pearson's product movement correlation coefficient was calculated
      based on the results produced by two separate experienced testers. (3) As to test
      stability, reliability was determined through repetitive testing.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1389327
TI  - [Ataxic cerebral palsy and brain imaging].
AB  - Five cases diagnosed as having ataxic cerebral palsy were presented with their
      brain imaging. Case 1, a 3-year-old-girl had been floppy since 7 months of age
      and began ataxic walk with spastic legs from 18 months of age. MRI revealed
      generalized atrophy of cerebellum (especially in anterior superior part) and
      slight atrophy of pons. Her mother also had ataxia with spastic legs of early
      onset. She and her mother were thought to have an early-onset inherited non
      progressive cerebellar ataxia syndrome. Case 2, a 8-year-old-girl had ataxic walk
      since 17 months of age. MRI revealed cerebellar atrophy especially in anterior
      superior part. Case 3, a 10-year-old boy was floppy since 4 months of age and
      suspected as ataxic at 4 years of age. He could walk only with cruches. He had
      dwarfism and cataracts since 4 years of age. CT and MRI revealed generalized
      spino-ponto-cerebellar atrophy. Final diagnosis was Marinesco-Sjorgren syndrome.
      Case 4, a 10-year-old girl had opisthotonus and floppiness since 4 months of age.
      She could walk only with cruches. CT and MRI revealed generalized spino-ponto
      cerebellar atrophy. Case 5, a 8-year-old boy showed head nodding and nystagmus
      since 4 months of age. He started ataxic gait at 8 years of age. He could
      vocalize only single sound for speech. MRI revealed cranium bifida and agenesis
      of anterior medullar velum. Ataxic cerebral palsy is the term often used to
      describe very different conditions, the clinical picture starts as hypotonia and
      changes into the ataxic symptoms in a few years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389328
TI  - [Quantification of electroencephalogram continuity by 24-hour recording in very
      premature infants].
AB  - We aimed to quantify electroencephalogram (EEG) continuity for 24 hours in very
      premature infants. A total of 122 days of continuous two-channel EEG recordings
      were performed in 28 premature infants from 26 to 33 weeks of conceptional age
      (CA). None of the infants showed any evidence of neurological impairments during
      the course of their hospitalizations and showed normal neurological outcome. The
      24-hour EEG recording was divided into 5.5-minute periods. The EEG of each period
      was classified into five EEG categories according to EEG continuity, and the
      percentage of each of them during the 24-hour recording was calculated. The
      percentages of continuous and continuous dominant EEG categories were increased
      with increasing CA. On the other hand, the percentages of discontinuous and
      discontinuous dominant EEG categories were decreased with increasing CA.

PMID- 1389329
TI  - [Relationship between developmental prognosis and changing picture of postural
      findings in early infancy among early treated children].
AB  - We followed 93 infants prospectively who were treated because of moderate and
      severe grades of cerebral coordination disturbances since less than 6 months of
      age. They were divided into 3 groups according to developmental prognosis at 4
      years of age; normal 44, mental retardation 18, and cerebral palsy 31. We
      compared the postural findings in supine and prone position, and 7 postural
      reactions at the first examination with those at discharge about 50 days after
      the first examination. We assessed the changing pictures of postural findings as
      improved, not changed or worsened. We analyzed the relationship between the
      changing pictures of postural findings during the short period in early infancy
      and the developmental prognosis among the 3 groups. The normal group showed
      improvement in a larger number of items than the other two groups. The findings
      of cerebral palsied children showed poor improvement, and more postural reactions
      changed to be more pathologic than those in the other two groups. Among the
      cerebral palsied children, ambulatory cases showed better improvement than those
      who could not crawl. But we found no significant difference between ambulatory
      and crawling children. This study demonstrated that assessment of changing
      pictures of postural findings in early infancy was helpful to predict
      developmental prognosis.

PMID- 1389330
TI  - [N-isopropyl-p-[I123] iodoamphetamine single photon emission computed tomography
      (I123-IMP SPECT) and child neurology].
AB  - We studied the clinical usefulness of I123-IMP SPECT in 50 pediatric patients
      with CNS disorders, which were categorized into the convulsive disorder group (n
      = 20), the cerebrovascular disorder group (n = 10), the acute encephalopathy or
      CNS infection group (n = 10), the metabolic or degenerative disorder group (n =
      6), the congenital abnormality group (n = 2) and the migraine group (n = 2). The
      findings obtained were compared with those of cranial CT. I123-IMP SPECT revealed
      abnormal findings in 45 out of the 50 patients (90%), although cranial CT showed
      abnormal findings in only 24 patients (48%). This difference was statistically
      significant (p less than 0.01). In all groups except the migraine, we could find
      abnormal findings in more than 90% of the patients. Out of 28 patients without
      focal findings on the initial CT scanning, I123-IMP SPECT showed focal
      abnormalities in 26 patients (93%). Moreover in many patients with focal
      neurological abnormalities, we found focal abnormalities of I123-IMP SPECT
      related with neurological abnormalities of the patients. From these findings, we
      think I123-IMP SPECT might be better to CT scanning in examining a localized
      lesion. It was found that in many patients with focal abnormalities in CT
      scanning, I123-IMP SPECT showed larger abnormalities in CT scanning. By using
      I123-IMP SPECT we might be able to study the blood perfusional state surrounding
      the abnormal area shown by CT. In 3 patients with acute cerebrovascular
      disorders, I123-IMP SPECT revealed abnormal findings 3 to 11 days earlier than
      cranial CT.I123-IMP SPECT might be useful for early recognition of the
      pathological state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389331
TI  - [A case of frontal lobe epilepsy presenting with gelastic seizures].
AB  - We described a 9-year-old boy with frontal lobe epilepsy presenting with gelastic
      seizures. CT-scan showed mild widening of the left sylvian fissure. Abnormal
      findings in the left frontal operculum were detected by both MRI and SPECT.
      Attacks mainly consisted of gelastic seizures with comfortable feeling followed
      by screaming with fear. Administration of anticonvulsants resulted in reducing
      the frequency and severity of seizures. Finally the patient had brief laughter
      attacks only. In the present case, the clinical course suggests that the gelastic
      seizures does not occur by way of the spreading of epileptic discharges to the
      temporal or hypothalamic region; rather it might occur as a focal symptom of the
      frontal region.

PMID- 1389332
TI  - [A case of cardiac arrest encephalopathy in athetotic cerebral palsy].
AB  - A 25-year-old woman with cerebral palsy of spastic quadriplegia and athetosis
      showed typical cardiac arrest encephalopathy on neuropathology. The etiology of
      cerebral palsy was perinatal origin including prematurity, asphyxia and
      hyperbilirubinemia. Ventricular premature beats had developed since about 20
      years of age. Muscle tone also increased with aging and symptoms of vago-vagal
      reflex were occasionally observed after eating. At 25 years, cardiac arrest
      occurred and cardiopulmonary resucitation was done immediately. She remained
      unconscious with absent corneal reflex and irregular respiration. EEG or auditory
      brain stem response showed flat activity. She died of respiratory failure 53 days
      after the episode of cardiac arrest. Neuropathology showed bilaterally
      symmetrical necrosis in the superior colliculi, gracilis nuclei, cuneate nuclei
      and spinotrigeminal nuclei accompanied with severe necrosis in the cerebrum and
      cerebellum. These findings in this adult case of total asphyxia were compatible
      with those observed in total plus partial asphyxia in the neonates. This
      discrepancy may be due to difference in cerebral maturity. Children or young
      adults with athetotic type cerebral palsy have a high risk of sudden death.
      Sudden cardiac arrest seems to play an important role in sudden death of these
      patients.

PMID- 1389333
TI  - [Infantile spasms in monozygotic twins with Smith-Lemli-Opitz syndrome type I].
AB  - Monozygotic twins with Smith-Lemli-Opitz syndrome who developed infantile spasms
      were presented. They were the result of the first full-term pregnancy of non
      consanguineous parents. They had following abnormalities: marked growth and
      developmental retardation, congenital heart disease, light brown hair which is
      rare in Japanese, small dolichocephaly, hypertelorism, anteverted nostrils,
      micrognathia, hypospadias and shawl scrotum. The cranial MRI showed the delayed
      myelination of occipital lobe. As far as we could review published reports, we
      were unable to find other report on monozygotic twins having the Smith-Lemli
      Opitz syndrome.

PMID- 1389334
TI  - [MRI as an aid for diagnosis of infantile neuroaxonal dystrophy].
AB  - We experienced a 5-year-old girl, who had presented with nystagmus and
      psychomotor regression since 1 year old. No clinical diagnosis had been made
      despite various examinations including lysosomal enzymes and muscle biopsy. Her
      brain magnetic resonance imaging (MRI) revealed increased a T2 signal in
      bilateral cerebellar hemisphere. Recently this MRI finding was reported as a
      typical feature of infantile neuroaxonal dystrophy (INAD). Then we performed the
      second biopsy from her peripheral nerve, and diagnosed her as having INAD. It was
      suggested that MRI was a useful aid for the diagnosis of INAD.

PMID- 1389335
TI  - [Identification of pivaloylcarnitine in urine of patients with pivoxil therapy].

PMID- 1389336
TI  - [Muscle CT in Duchenne muscle dystrophy in infants].

PMID- 1389337
TI  - Alkaline phosphatase inhibitors as labels of DNA probes.
AB  - A new approach to nucleic acid labeling was developed by preparing bifunctional
      reagents containing, in addition to the DNA-linking group, a competitive
      inhibitor of the chromogenic enzyme alkaline phosphatase. The nucleic acids
      labeled in such a way were able to bind themselves to the enzyme, whose activity
      was restored in the presence of a chromogenic substrate. Five phosphonic-acid
      containing reagents were synthesized and coupled to linearized pBR322 plasmid DNA
      by different condensation methods. Eight probes thus obtained were assayed in a
      modified dot-blot detection procedure obtaining the best nucleic acid detection
      sensitivity of 25 pg. Finally, five of the above probes were tested in
      hybridization experiments, reaching sensitivity of 50 pg.

PMID- 1389338
TI  - Direct DNA hybridization screening of primary yeast transformants in the
      construction of targeted yeast artificial chromosome (YAC) libraries.
AB  - A simple and inexpensive method for direct, large-scale DNA hybridization
      screening of primary yeast colonies following introduction of foreign DNA into
      Saccharomyces cerevisiae by spheroplast transformation is presented. An optimally
      thin layer of standard regeneration agar containing the transformed spheroplasts
      is spread on selective plates using carefully controlled temperature conditions;
      the colonies regenerate initially within the thin layer of hardened regeneration
      agar, but as they grow, greater than 90% of them break the surface and become
      accessible to direct lifting and screening methods. The technique avoids the
      manual or mechanized picking of transformants from within the regeneration top
      agar, does not require specialized (and often expensive) regeneration matrices
      such as alginate or low-melting-point agarose, and yields transformation
      efficiencies and screening results identical to those obtained using the standard
      spheroplast transformation protocol. We demonstrate the utility of this method
      for the construction of a targeted human-YAC library from a hamster hybrid cell
      line that contains chromosome 13 as its only human DNA.

PMID- 1389339
TI  - Detection of individual human chromosomes by chromosome in situ suppression
      hybridization using PCR-amplified bacteriophage library probes.
AB  - We used the polymerase chain reaction (PCR) to prepare chromosome-specific probes
      from the bacteriophage lambda library LAO1NS01, prepared at the Los Alamos
      National Laboratory from flow sorted human chromosome 1. By using oligonucleotide
      primers flanking the EcoRI insertion site of the Charon 21A vector, we were able
      to amplify the human sequences preferentially in the library up to 9.1 kb
      (maximum insert size). The product of the PCR reaction was nick translated with
      incorporation of biotinylated residues and used with fluorescence in situ
      hybridization to observe metaphase chromosomes by fluorescence microscopy. This
      technique allows for a relatively easy method for preparation of chromosome
      specific library probes for "chromosome painting." The quality of the results
      obtained by this method compares favorably to those obtained by using bulk
      purified library inserts. This method offers potential advantages in terms of
      cost and ease of use.

PMID- 1389340
TI  - Microleakage evaluation in amalgam restorations used with bases.
AB  - Marginal leakage in amalgam restorations often precedes the development of
      secondary caries. One potential way to improve the marginal seal of such
      restorations, and thus minimize the risk of caries development, is to apply a
      glass-ionomer base prior to amalgam placement. This study compared microleakage
      resistance among amalgam restorations placed with and without light-cured glass
      ionomer base materials. Preparations were made in extracted human molar teeth.
      Four groups were studied, including copal varnish, which was used as a control.
      All specimens were restored with amalgam. Results indicated significantly greater
      leakage at the cavity wall/base interface for restorations with a copal varnish
      cavity liner than for those with a glass-ionomer base. Leakage differences among
      bases were also found at the amalgam/base interface. Best results were obtained
      with a dual-cure resin-based system. These samples showed minimal leakage at both
      the cavity wall/base and the base/amalgam interfaces. These findings suggest that
      light-cured glass-ionomer bases can be effective in the prevention of
      microleakage in amalgam restorations.

PMID- 1389341
TI  - Addition of fresh amalgam to existing amalgam: microleakage study.
AB  - The purpose of this in vitro study was to determine whether adhesive lining
      materials reduce microleakage in amalgam restorations, and to observe the degree
      of microleakage at the interface between freshly placed (new) and existing (old)
      amalgam. Forty-eight specimens were used in the experimental groups. The
      materials used to study microleakage in this investigation were: copal varnish, a
      dentin bonding agent (Clearfil New Bond), and a 4-META adhesive (Amalgambond). No
      significant difference in microleakage was found at the interfaces between
      freshly placed and existing amalgam. Significantly less microleakage was noted in
      specimens using the 4-META adhesive and the dentin bonding agent as compared to
      specimens in which no lining material was placed. Significantly less microleakage
      was noted in specimens using the 4-META adhesive compared to specimens using
      cavity varnish.

PMID- 1389342
TI  - Bonding fresh amalgam to existing amalgam: a shear and flexural strength study.
AB  - The purpose of this study was to compare the shear and flexural strength obtained
      when various adhesives or liners were used to bond freshly placed amalgam to
      existing amalgam. The adhesives used in this study were the following: cavity
      varnish, 4-META adhesive (Amalgambond), and a dentin bonding agent (Clearfil New
      Bond). After samples were fabricated, shear bond strengths were determined by
      using an Instron Testing Machine, and flexural strengths determined using a
      Material Test System (MTS) testing machine. All test groups produced shear and
      flexural strengths less than one half of the control group. The dentin bonding
      agent and the 4-META adhesive produced significantly higher shear and flexural
      strengths than the test group in which no lining material was used.

PMID- 1389344
TI  - Bonded silver amalgam restorations.
AB  - Although silver amalgam is a strong, stable, technique-insensitive material, its
      use requires the removal of more intact tooth structure than adhesive materials
      in order to provide long-term retention. Thus remaining tooth structure is
      weakened rather than strengthened. Bonded silver amalgam restorations, on the
      other hand, have excellent retention, don't require pins, strengthen remaining
      tooth structure, eliminate the likelihood of cuspal fracture, and eliminate
      postoperative sensitivity.

PMID- 1389343
TI  - Addition of fresh amalgam to existing amalgam utilizing various adhesive liners:
      a SEM study.
AB  - The purpose of this study was to observe the interfaces between (1) dentin and
      amalgam and (2) freshly placed amalgam and existing amalgam using various
      adhesive liners. Specimens were randomly assigned to four equal groups for liner
      placement: Group I--control, no liner used; Group II--copal varnish; Group III--4
      META adhesive; Group IV--dentin bonding agent. After liner placement and amalgam
      replacement, specimens set for 24 hours and were then thermocycled in 0.5% basic
      Fuchsin dye, sectioned, and SEM analyses performed. Microgaps appeared in a
      disjointed fashion at the interface between freshly placed and existing amalgam.
      The 4-META adhesive appeared to establish a bond between amalgam and tooth
      structure and, thus, diminished the microgap between amalgam and dentin.

PMID- 1389346
TI  - Amalgam as a restorative material: is there anything new?
AB  - The properties of a new, dispersed-phase amalgam containing admixed indium
      (Indisperse) are reviewed. Laboratory tests show that the addition of indium
      significantly improves the strength and the resistance to creep and corrosion of
      the amalgam, and that mercury release from the amalgam is markedly reduced. A 5
      year clinical study shows a lower frequency for marginal breakdown for Indisperse
      compared to other dispersed-phase amalgam containing no admixed indium.

PMID- 1389345
TI  - Hydrolysis of 4-META/MMA-TBB resins: a myth.
AB  - Recently, it has been erroneously reported that adhesive bonds to various
      substrates produced with 4-META/MMA-TBB type resins degrade by hydrolysis. This
      paper dispels this myth. The author cites a number of independent research
      studies indicating that bonds mediated by 4-META/MMA-TBB systems are extremely
      stable when subjected to extensive thermocycling in a wet environment.

PMID- 1389347
TI  - Esthetic diagnosis.

PMID- 1389348
TI  - Checking the reliability of your curing light.

PMID- 1389349
TI  - Bleaching and/or porcelain veneers: case reports.
AB  - Four case studies are presented in which the concept that bleaching, porcelain
      veneer restorations, or a combination of both constitute a conservative treatment
      approach for discolored, malformed, malaligned, and worn dentition. These
      treatments can be used effectively not only for aging dentitions, but also for
      the very young, which makes them an attractive treatment modality.

PMID- 1389350
TI  - Bleaching teeth: history, chemicals, and methods used for common tooth
      discolorations.
AB  - This article reviews the history of bleaching teeth to lighten tooth color. The
      last 2 years have seen a dramatic increase in new bleaching methods and bleaching
      chemicals. The following categorizes bleaching chemicals and methods in relation
      to their use in treating common tooth discolorations. Special attention is given
      to home bleaching methods.

PMID- 1389352
TI  - Vital bleaching agents and oral antiseptic: effect on anaerobic bacteria.
AB  - This in vitro study compared the antimicrobial effect of several at-home
      bleaching agents and an oral antiseptic against anaerobic bacteria that are
      commonly found in the oral cavity. Zones of inhibition produced by Rembrandt
      Lighten Bleaching Gel, Opalescence, and Peroxyl were measured and compared. All
      the materials produced zones of inhibition with the five bacteria used in the
      study.

PMID- 1389351
TI  - Double-blind whitening Night-Guard study using ten percent carbamide peroxide.
AB  - The conservative technique of professionally dispensed and supervised, home
      administered vital bleaching is now a routine treatment in the dental profession.
      This double-blind study evaluated the Rembrandt Lightening Gel and Whitening
      Toothpaste for shade change, colorimeter shade change. As well, it evaluated soft
      tissue health by periodontal probing, plaque index, and bleeding index. A patient
      questionnaire evaluated perception of whitening, perception of oral hygiene,
      average hours per day, and average days per week. Bleaching trays were worn over
      a 4-week period. The bleaching system showed definitive whitening effects as
      evaluated with the Vita shade guide and the colorimeter. The bleaching system had
      no deleterious effects on the soft tissue. The Rembrandt toothpaste alone
      demonstrated two-shade lightening. This vital bleaching system shows definitive
      whitening of the teeth in short periods of time with no adverse effects.

PMID- 1389353
TI  - At-home bleaching system: effect on gingival tissue.
AB  - This study evaluated the effects of an at-home vital bleaching system on gingival
      responses over a 6-week period. Objective measures were utilized to measure and
      monitor gingival inflammation over this period of time. Vital bleaching was
      performed as follows: (1) bleaching gel in a prefabricated mouthguard and (2) an
      ad-mix technique--bleaching gel and toothpaste in a 1:1 ratio. In addition a
      control group used a placebo in a prefabricated mouthguard. The at-home vital
      bleaching system produced no adverse gingival tissue responses. Furthermore, the
      at-home vital bleaching system helped produce a therapeutic effect on inflamed
      gingival tissues over the course of the study.

PMID- 1389354
TI  - Vital bleaching: a new light-activated hydrogen peroxide system.
AB  - With ever increasing interest in cosmetic enhancement of dentition by dentists
      and patients alike, this article introduces a new light-activated bleaching
      system that adds up to total patient satisfaction and reduced chair time. The
      chairside application of hydrogen peroxide 30% was effective in lightening a
      moderate case of tetracycline staining. The uniqueness of this system allows the
      practitioner complete control within an office setting, and it provides the
      patient with an immediate result. The ease of application and strict supervision
      of a dentist has allowed this system to satisfy recent watchdogs of the Federal
      Drug Administration.

PMID- 1389356
TI  - Total etch technique and cavity isolation.
AB  - In the total etch technique for chemically adhesive composite restorations, the
      phosphoric acid penetrates only 10 microns or less into the vital dentin with the
      dentinal tubules being filled with the odontoblast processes. The acid is
      completely removed by subsequent air-water jet spray washing. The tubule
      apertures are perfectly sealed by the protective bonding agent layer with the
      resin tags adhering to the tubule walls and the resin-impregnated dentin surface.
      Isolation of the cavity from moisture contamination is required for only less
      than a few seconds after drying the etched cavity until the bonding agent coating
      and after this coating until the composite resin placement. Such a short time for
      isolation is quite easy even without a rubber dam when a trained assistant is
      cooperating.

PMID- 1389355
TI  - Restoring the worn dentition.
AB  - Strong dental materials and dental porcelains are providing dentists with
      restorative opportunities that are more conservative because they require less
      destruction of healthy tooth structure and yield a more esthetic result. In cases
      of severe wear due to attrition, abrasion, and erosion, this process can be
      stopped, restoring the esthetics and function by using proper techniques and
      materials. The case report described in this article demonstrates the
      conservative restoration of severe wear due to attrition and erosion. Teeth were
      lengthened, wear was restored, and further wear was ceased by using a combination
      of bonded porcelain, a heat, light, and self-cure resin system, and a new glass
      ionomer restorative material. The result was a strong, durable restoration (that
      required no anesthesia) with high esthetics.

PMID- 1389357
TI  - Repair of porcelain/metal restoration with resin bonded overcasting.
AB  - Porcelain occasionally fractures from ceramometal fixed partial dentures
      following final cementation. Repair of these porcelain fractures can be a
      challenging task. When the problem occurs on anterior teeth, it is especially
      difficult because the repair must not only be durable, but esthetically pleasing
      as well. Although composite resins can be used for some repairs, it is often
      difficult to match the color and texture to the surrounding intact porcelain. In
      addition, the bonding between the resin and porcelain is susceptible to margin
      leakage, which may ultimately cause an esthetic failure. Techniques involving a
      cemented porcelain-fused-to-metal overcasting have often been successful in
      restoring the fixed partial denture to form and function. Although the esthetic
      result of a porcelain/metal overcasting can be quite successful, retention of the
      overcasting is sometimes poor. The compromised retention and resistance form is
      due to lack of interproximal walls on the underlying fractured unit. To improve
      the retention of the overcasting, the following technique of tin plating the
      overcasting and fractured unit prior to cementing with a composite resin cement
      is presented.

PMID- 1389358
TI  - Microleakage between glass-ionomer cement and composite resins.
AB  - This study investigated the microleakage between glass-ionomer cement and Silux
      or Herculite with and without Scotchbond 2. Cavities were prepared in polymerized
      composite resin samples and "restored" with a glass ionomer cement with and
      without Scotchbond 2. The samples were thermocycled and immersed in 0.05% crystal
      violet solution for 2 hours, then embedded in clear casting resin, sectioned, and
      examined with an optical microscope. The results indicated that a high degree of
      dye penetration was found in samples of GC and Silux, and GC and Herculite
      without Scotchbond 2. The use of Scotchbond 2 significantly reduced the degree of
      dye penetration, but did not completely eliminate dye penetration.

PMID- 1389359
TI  - Shear bond strengths of resin adhesive cements to dentin and Ni-Cr-Be alloy.
AB  - Two adhesives, Super Bond and Panavia, were evaluated for shear bond strength to
      dentin. Twenty human teeth were used for each adhesive. Bonding sites were
      prepared in dentin (600 grit) and the adhesives applied according to the
      manufacturers' instructions. Bond strengths were determined with an Instron
      testing machine at 24 hours. Super Bond developed the strongest bond of 21.59 +/-
      3.91 MPa. Panavia produced a lower bond strength of 2.68 +/- 1.45 MPa.
      Statistically, Super Bond was found to have a stronger bond than Panavia. The
      same two adhesives were applied to Ni-Cr-Be specimens and compared to Comspan.
      Twenty Rexillium III specimens were used for each adhesive at 24 hours and 20 for
      thermocycling. The metal specimens were ground flat (600 grit) and then air
      abraded with 50-micron aluminous oxide. The adhesives were applied to the metal
      surface in accordance with the manufacturers' instructions. One group was tested
      at 24 hours while the second group was tested after thermocycling (2,500 cycles
      at 6 degrees C to 60 degrees C). At 24 hours, Super Bond had a significantly
      stronger bond than the other materials. Comparison of the 24-hour to thermocycled
      bond strengths found Comspan had a significant increase in bond strength, Panavia
      had no significant change and Super Bond had a significant decrease in bond
      strength. After 2,500 thermocycles, Comspan, Panavia, and Super Bond were not
      significantly different in bond strength.

PMID- 1389360
TI  - In vitro effect of topical fluorides on sealant materials.
AB  - The purpose of this study was to determine by visual inspection and by scanning
      electron microscopy (SEM) whether commercially available, topical, acidulated
      phosphate fluoride (APF) and neutral sodium fluoride (NaF) agents cause surface
      roughening of five sealant materials: two unfilled resins, two filled resins, and
      one glass-ionomer material. In addition, the effect of treatment with 1.23% APF
      and sonification on weight of an unfilled and a filled sealant was compared to
      treatment with controls. Unfilled sealants exhibited no surface changes visually
      or on micrographs following any treatment. Filled sealants and the glass-ionomer
      sealant exhibited visually apparent changes depending on the treatment. SEM
      inspection of filled sealants with visually apparent changes showed loss of
      filler particles whereas the glass-ionomer sealant exhibited apparent destruction
      both of the matrix and the filler particle. No significant differences in weight
      were found between sonicated and unsonicated specimens. However, significant loss
      of weight was found with filled sealant specimens, but not unfilled sealant
      specimens, treated with 1.23% APF gel as compared with the specimens treated with
      water. The results of this in vitro study indicate that preventive therapies that
      combine use of topical fluorides and sealants may cause deterioration of filled
      sealants and glass-ionomer sealant material, but not unfilled sealants.

PMID- 1389361
TI  - Ranking of facial profiles among Asians.
AB  - The purpose of this study was to determine the facial profile preferences in a
      sample of 1,189 Asian teenagers (aged 15.3 +/- 3.2 years). Five facial profile
      types were computer-generated by trained personnel (orthodontists and oral
      maxillofacial surgeons) to represent distinct facial types. Subjects were asked
      to rank the profiles in descending order of attractiveness. The ranking was as
      follows: orthognathic profile, bimaxillary retrusive profile, bimaxillary
      protrusive profile, mandibular retrognathic profile, and mandibular prognathic
      profile. The differences in rank scores between all the profile types were
      statistically significant (p < 0.05). Assessment of profile types among lay
      personnel could provide clinicians an indication into the relative attractiveness
      among profile types and health care workers in treatment prioritization among
      dysmorphic facial types.

PMID- 1389362
TI  - Porcelain to dentin bond strength with a dentin adhesive.
AB  - Adhesion of porcelain to dentin may be important in those cases with little
      remaining enamel. The purpose of this study was to determine the bond strength of
      porcelain to dentin using a dentin adhesive (All-Bond) and compare it to the
      enamel bond strength. Sixty human molar teeth had either a dentin or enamel
      bonding site prepared by flat grinding to a 600 grit. The teeth were divided into
      three groups of 20 each. Sixty porcelain cylinders were prepared, hydrofluoric
      acid etched on one end and silane treated. Twenty of the cylinders were bonded to
      enamel, 20 bonded to dentin with a dentin adhesive to be tested at 48 hours, and
      20 bonded to dentin with a dentin adhesive to be tested after 24 hours of
      thermocycling (800 cycles at 6 degrees C to 60 degrees C). The specimens were
      tested in an Instron at a crosshead speed of 0.5 mm/minute. The following bond
      strengths were found: enamel (19.0 +/- 2.9 MPa), dentin at 48 hours (14.4 +/- 5.4
      MPa), and dentin after thermocycling (10.1 +/- 3.8 MPa). When this data was
      subjected to statistical analysis (ANOVA), there was a significant difference
      between the groups. A Scheffe's test found that the dentin-porcelain bond at 48
      hours was stronger than the thermocycled group, and that the enamel bond was
      significantly stronger than the two dentin bonds.

PMID- 1389363
TI  - Diastema preservation in resin-bonded fixed partial dentures.
AB  - The etched-metal, resin-bonded fixed partial denture has evolved rapidly from its
      origination as an extracoronal splint. Technologic advancements in both resin
      chemistry and retentive surface etching techniques have markedly improved the
      quality of the prosthesis. Today, resin-bonded fixed partial dentures are an
      effective, conservative means of replacing missing teeth when specific contra
      indications--long spans, insufficient sound enamel, malocclusion, pathologic
      occlusal habits--are identified and avoided. A universally-accepted standard
      preparation does not exist for resin-bonded fixed partial dentures; rather,
      common principles of tooth reduction are agreed upon by most authors. This case
      report details necessary modifications in typical preparation and framework
      design that must be included to maintain a midline diastema when such spacing is
      required or preferred by the patient.

PMID- 1389365
TI  - Professional nursing and Rogerian nursing science in New Zealand.

PMID- 1389364
TI  - New concepts with bases and liners.

PMID- 1389366
TI  - The lived experience of schizophrenia.

PMID- 1389367
TI  - The state of the society address.

PMID- 1389368
TI  - Acoustic rhinometry: a diagnostic tool for patients with chronic rhonchopathies.

PMID- 1389369
TI  - Therapeutic performance of nasal and paranasal operations in recent years.
AB  - In this survey of the postoperative therapeutic performance of 555 cases of nasal
      surgery, particularly conservative fiberscopic endonasal sinusectomy, it was
      found that conservative nasal operations accounted for 87.8% of the entire sample
      population and the therapeutic effects, (in terms of subjective symptoms) were
      found to be favorable in 91.5% of cases. These results suggest that conservative
      nasal operations will become the dominant form of nasal surgery in the future.

PMID- 1389370
TI  - Migraines and the sinuses, report on 441 cases.

PMID- 1389371
TI  - Complications of the maxillary sinus irrigation caused by misdirected tip of the
      trocar.

PMID- 1389372
TI  - Otitis media. Sinus-related problems.

PMID- 1389373
TI  - Computed tomography: anatomical aspect.

PMID- 1389374
TI  - Computed tomography in rhinology.

PMID- 1389375
TI  - Ultrasonography of paranasal sinus lesions.

PMID- 1389377
TI  - Merit and demerit of endoscopic surgery.

PMID- 1389376
TI  - Drug resistance in bacteria: history, genetics, biochemistry.

PMID- 1389378
TI  - Technical problems in endoscopic sinus surgery.

PMID- 1389379
TI  - Endoscopic sinus surgery--complications and how to avoid them.

PMID- 1389380
TI  - Postoperative care and long term results.

PMID- 1389381
TI  - Clinical significance of 3-dimensional computed tomography (3-D CT) performed in
      maxillofacial trauma.

PMID- 1389382
TI  - Surgical management of midfacial fractures.
AB  - A brief overview has been given about types, diagnostics and therapy of midfacial
      fractures. The ENT-surgeon should play an important and active role in the
      treatment. In extended cases interdisciplinary cooperation will give better
      results.

PMID- 1389383
TI  - Orbital wall fractures.

PMID- 1389384
TI  - Fireside conference 2. Pathogenesis of nasal polyps.

PMID- 1389386
TI  - Fireside conference 5. Turbinate problems.

PMID- 1389387
TI  - Fireside conference 6. Immotile cilia syndrome and sinobronchial syndrome.

PMID- 1389385
TI  - Fireside conference 4. Endoscopy in the nose.

PMID- 1389388
TI  - Fireside conference 7. Immunotherapy for allergic rhinitis.

PMID- 1389389
TI  - Fireside conference 8. Cancer of the nose.

PMID- 1389391
TI  - Fireside conference 10. Radical sinus surgery--new trend.

PMID- 1389390
TI  - Fireside conference 9. Cosmetic nasal surgery.

PMID- 1389392
TI  - Fireside conference 12, Mucociliary transport test.

PMID- 1389393
TI  - Fireside conference 13. Olfactory function test.

PMID- 1389394
TI  - Fireside conference 14. Nasal provocation test.

PMID- 1389395
TI  - Fireside conference 15. Sleep apnea syndrome.

PMID- 1389396
TI  - Fireside conference 17. The mind in rhinology.

PMID- 1389397
TI  - Fireside conference 18. Functional nasal surgery.

PMID- 1389398
TI  - Fireside conference 19. Wegener's granulomatosis and lethal midline granuloma.
AB  - In summary, Wegener's granulomatosis is a systemic illness that is characterized
      pathologically by necrotizing granulomatosis and vasculitis. Lethal midline
      granuloma is not a pathological term. Lethal midline granuloma is a clinical
      term, and in reality, lethal midline granuloma has been proven to be polymorphic
      reticulosis and not Wegener's granulomatosis. Polymorphic reticulosis is now
      understood to be a T-cell lymphoma. Further study of these malignant lymphomas
      has shown that these T-cell lymphoproliferative disorders may be causally
      associated with Epstein-Barr virus. Although there is strong association between
      autoantibodies against cytoplasmic constituents of neurophils and monocytes in
      patients with active Wegener's granulomatosis, the exact pathogenic mechanism in
      Wegener's granulomatosis and the etiology is still unknown. IgG-C-ANAC (C-ANAC
      stands for Classical/Cytoplasmic Anti-Neutrophil Cytoplasm Antibodies) increases
      with increasing disease activity from undetectable levels to up to 95% of active
      Wegener's granulomatosis patients. Rhinologic symptoms in Wegener's
      granulomatosis include progressive nasal obstruction, bloody rhinorrhea with
      crusting, and vague pain and tenderness of the nasal dorsum. Usually these
      patients have mucosal ulcerations of the nose with or without a septal
      perforation. Other areas of the head and neck can be involved, and they include
      orbital, otologic, oral, and subglottic involvement. Hallmarks of malignant
      lymphoma (polymorphic reticulosis) when it involves the upper airway include
      rapid localized destruction of the nose, orbit, paranasal sinuses, and hard
      palate. Treatment for Wegener's granulomatosis includes antimicrobial agents in
      addition to a regimen of cyclophosphamide and glucocorticoids. The treatment for
      malignant lymphoma (polymorphic reticulosis) is primarily radiation, especially
      when confined to one site.

PMID- 1389399
TI  - Immunochemical aspects of mucosal immunity of the nose.

PMID- 1389400
TI  - Cellular aspects of nasal immunology.

PMID- 1389401
TI  - Ciliary beat harmony another parameter for ciliary function.

PMID- 1389402
TI  - Pathophysiology of the nasal mucosa.

PMID- 1389403
TI  - The impact of immunotherapy on the pathophysiology of ragweed pollen allergy.

PMID- 1389404
TI  - In human nasal mucosa, interleukin-5 accumulates and degranulates eosinophils, as
      well as increases responsiveness to histamine.

PMID- 1389405
TI  - Blood flow in the allergic nasal mucosa.

PMID- 1389406
TI  - Topical use of antibiotics for paranasal sinusitis.

PMID- 1389407
TI  - Nasal airway resistance and nasal sensation of airflow.
AB  - Nasal obstruction is a common symptom which is most frequently associated with an
      increased nasal airway resistance. However it is important to appreciate that the
      objective measurement of nasal airway resistance does not always correlate with
      the subjective perception of the degree of nasal obstruction. Damage to
      trigeminal sensory nerve endings can cause a sensation of nasal stuffiness
      without any change in nasal airway resistance and similarly inhalation of menthol
      can cause a subjective improvement in nasal sensation of airflow without any
      change in nasal resistance.

PMID- 1389408
TI  - Clinical application of computerized rhinomanometry.

PMID- 1389409
TI  - Clinical significance of rhinomanometric changes induced by exercise and
      decongestants.

PMID- 1389410
TI  - [Septic complications of vena cava filter implantation].

PMID- 1389411
TI  - [Repeated heart valve replacement].

PMID- 1389412
TI  - [Surgical techniques of combined operations on coronary arteries and arteries of
      the lower limbs].
AB  - Experience has been accumulated in the department in the surgical treatment of
      165 patients with combined affections of the coronary arteries and the arteries
      of the lower limbs. One-stage operations were conducted on 14 patients due to
      clinically severe ischemia of the heart and limbs. A bifurcation aortofemoral
      shunt with an aortocoronary shunt was formed in 2 patients. In the other cases an
      aortocoronary shunt without or with resection of a heart aneurysm and various
      types of aorto-iliac-femoral and femoropopliteal reconstructions were performed.
      No hospital mortality was encountered. The surgical techniques of combined
      operations are described in detail. It is concluded that such surgical
      interventions should be conducted only in highly-qualified institutions
      possessing rich experience both in coronary and in vascular operations.

PMID- 1389413
TI  - [Effect of different types of pharmacocryocardioplegia on the occurrence of
      cardiac rhythm and conduction disturbances in the early postoperative period in
      patients with ischemic heart disease].
AB  - 109 patients who underwent operation for formation of an aortocoronary shunt
      (ACS) were divided into 3 groups according to the method of introducing a
      cardioplegic solution and reperfusion. Thirty-five patients (group 1) underwent
      antegrade cardioplegia and direct reperfusion. Thirty-seven (group 2) were
      subjected to mixed antegrade-retrograde cardioplegia. Group 3 consisted of 37
      patients with myocardial protection accomplished by the same method as in group
      2, but retrograde perfusion was with warmed oxygenated blood through the right
      atrium was conducted before removing the clamp from the aorta. The effect of
      various types of pharmacocryocardioplegia on the appearance of new disorders of
      rhythm and conductivity in the early postoperative period after ACS formation was
      analysed. The frequency of sinus tachycardia was less in group 3 (24%) than in
      groups 1 and 2 (51 and 51%, respectively, p less than 0.05). We obtained no
      statistically significant differences in the frequency of other types of
      arrhythmias in these 3 groups. However, the number of transient bundle-branch
      blocks and disorders of intraventricular conductivity (8.1 and 10.8%,
      respectively) in group 3 was also less than that in groups 1 and 2 (p less than
      0.05) and their regression was faster. We believe that combined anterograde
      retrograde cardioplegia applied together with retrograde reperfusion with warmed
      oxygenated blood is most effective not only in protection of the conduction
      system of the heart but also in protection of the right- and left-ventricular
      myocardium.

PMID- 1389414
TI  - [Proximal anastomosis in surgery for Leriche's syndrome].
AB  - The author analysed the frequency of different variants of atherosclerotic
      affection of the aortoiliac-femoral segment in 300 patients who underwent
      operation. With consideration for these data, the surgical tactics and techniques
      of proximal anastomosis in aortofemoral shunting (prosthetics) in 216 patients
      with variants of Leriche's syndrome are appraised. In most patients the operation
      may be carried out through an extraperitoneal approach. The choice of the type of
      proximal anastomosis in aortofemoral shunting (prosthetics) should be guided by
      the character of the affection, the condition of the branches of the abdominal
      aorta, and the necessity for revascularization of one or both extremities in one
      stage. The chosen tactics and techniques of the operation made it possible to
      preserve 86.1% of the vascularized extremities.

PMID- 1389415
TI  - [Evaluation of arterial insufficiency of the lower extremities according to
      oxygen transport values in the treadmill test].
AB  - The authors studied the possibility of evaluating peripheral arterial
      insufficiency according to the values of oxygen transport (consumption and oxygen
      debt) in the multistep treadmill test. Sixty patients with angiographically
      recognized affection of the vessels and 38 healthy individuals (controls) were
      examined. Both values were found to reflect the severity of arterial
      insufficiency of the lower limbs. The oxygen debt value was most informative in
      its evaluation. The degree of arterial insufficiency may be evaluated according
      to the level of the load in the treadmill test at the moment of inadequate oxygen
      debt occurrence.

PMID- 1389416
TI  - [Hospital infection in cardiovascular surgery ].

PMID- 1389417
TI  - [Emergency thoracoscopy in the diagnosis and treatment of complicated chest
      injury ].
AB  - Emergency thoracoscopy was undertaken in 111 patients with complicated closed
      chest trauma and in 67 persons with penetrating knife wounds of the chest.
      Thoracoscopy in patients with closed chest trauma revealed pneumohemothorax in
      53, pneumothorax in 42, and hemothorax in 10 cases, in 4 patients the hemothorax
      was coagulated. Penetrating injuries were complicated by pneumohemothorax in 30,
      by pneumothorax in 21, and by hemothorax in 16 cases. From the results of
      thoracoscopy, emergency thoracotomy was found to be indicated in 11 patients with
      penetrating chest wounds. Endoscopic electrocoagulation of the wounds of the lung
      and thoracic wall was conducted in 28 patients with a closed trauma and in 26
      persons with penetrating injuries, laser coagulation was performed in 10 cases
      with closed trauma and in 8 patient with knife wounds, medical glue was applied
      for occlusion of surface ruptures of the lung in 11 cases. No complications of
      thoracoscopy occurred. The therapeutic methods of thoracoscopy with the use of
      high frequency electric current, NIAH-laser radiation are described. It is
      concluded that the inclusion of thoracoscopy in the complex of therapeutic and
      diagnostic measures in patients with complicated chest trauma is expedient.

PMID- 1389418
TI  - [Effectiveness of hyperbaric oxygenation in the treatment of postresection
      bronchial fistulas].
AB  - The article discusses the results of treatment of 84 patients with postresection
      tuberculous pyothorax and bronchial fistulas with hyperbaric oxygenation session
      (HBO) included in the complex of therapeutic measures. As a result, the bronchial
      fistulas closed in 30 (35.7%) patients, the diameter of the fistulas reduced
      markedly in 20 (24.3%) patients, the bronchial fistulas failed to close in 40% of
      cases. As the result of HBO therapy the count of red cells and lymphocytes
      increased, leukocytosis and eosinophilia reduced, the ESR diminished. The content
      of ALT transaminase, sugar, total protein and bilirubin decreased. The migration
      index for all immune antigens in the reaction of leukocyte migration inhibition
      and in the nitro blue tetrazolium test increased. HBO promoted the efficacy of
      radical operations by 29.4% as compared to that in the control group of the
      similar patients.

PMID- 1389420
TI  - [Diagnosis and treatment of mediastinal neoplasms and cysts].
AB  - Possessing experience in the treatment of 314 patients with tumors and cysts of
      the mediastinum, the authors discuss problems of their diagnosis and surgical
      treatment. The patients' ages ranged from 7 to 64 years. Tumors were recognized
      in 216 (68.8%) and cysts in 98 (31.3%) patients. The radiological method,
      including computed tomography, is the main method for the diagnosis of
      mediastinal tumors and cysts. The presence of a pathological structure in the
      mediastinum is an indication for surgery independent of the development of
      complications. Operations for tumors and cysts of the mediastinum must be carried
      out in specialized medical institutions because they are complicated surgical
      interventions.

PMID- 1389419
TI  - [Comparative studies of immunologic characteristics in plasmapheresis and
      hemosorption in patients with purulent diseases of the lungs and pleura].
AB  - The article deals with the comparative characteristics of the changes in
      immunological indices in 40 patients with non-specific purulent diseases of the
      lungs and pleura when plasmapheresis and hemosorption were included in the
      complex of therapeutic measures. The changes were found to be hetero-directional
      in character: a non-specific effect of immunostimulation in hemosorption, and
      immunodepression, particularly marked in the first 24 hours, in plasmapheresis.
      The post-aggressive reaction after plasmapheresis is either absent or delayed
      significantly, which makes it possible to conduct detoxification in extremely
      grave conditions of the patients without making the mechanisms of the post
      aggressive reaction operative, as observed in performance of hemosorption.

PMID- 1389421
TI  - [Current methods of surgical treatment of gastroesophageal reflux].

PMID- 1389422
TI  - [Follow-up of a child with a common pleural cavity in combination with a funnel
      chest, displacement of the left lung into the right pleural cavity, and
      atelectasis of the left lung].

PMID- 1389423
TI  - [Esophageal leiomyoma in children].

PMID- 1389424
TI  - [Prevention and treatment of infectious complications in myocardial
      revascularization].
AB  - The study was conducted in a group of 440 patients who underwent planned
      operations for ischemic heart disease. Three current methods of preventive
      antibiotic therapy were compared. The influence of various risk factors on the
      incidence of infectious complications was analysed. Experience with closed
      mediastinitis management was also analysed. The effect of a short-term (1-3 days)
      course of claforan in prevention of infectious complications is the same as that
      of a 5-7-day course of cefamezin or gentamicin. Postoperative mediastinitis
      developed in 11 (2.5%) patients. It was managed in all patients by closed
      irrigation and drainage of the retrosternal space. The average duration of
      mediastinal irrigation was 7.4 days. Convalescence was attained in all cases.

PMID- 1389425
TI  - General practitioners' contract: the good, the bad, and the slippery slope.

PMID- 1389426
TI  - Usefulness of telephone consultations in general practice.

PMID- 1389427
TI  - Attitudes to medical care, the organization of work, and stress among general
      practitioners.
AB  - Eighty five volunteer general practitioners in Lothian region recorded clinical
      and contextual information on 21,000 consultations during 1987-88. During their
      recording sessions they reported their perceived levels of stress using a
      previously validated scale. Subsequently, 80 of the doctors completed a
      previously validated multi-dimensional scale about their attitudes to patient
      care. Three attitude subscales (psychological orientation, appropriateness of
      consultations and responsibility for decisions) correlated with processes of care
      previously identified as indicators of good care. The 20 doctors who scored most
      highly on these patient-centred scales recorded self-perceived stress in 27% of
      their consultations compared with 11% of the consultations of the 33 doctors who
      scored lowest on these scales. Among the 20 most patient-centred doctors those
      booking patients at eight patients per hour or more reported stress at twice as
      many consultations as those with a longer booking interval; doctors whose
      preferred working styles conflicted with their booking patterns reported stress
      in up to 62% of consultations. Doctors with a higher patient-centred orientation
      find their work more stressful. Longer booking intervals remove much of that
      stress, particularly when doctors' preferred style of consulting requires them to
      spend more time at individual consultations. Previously described work stressors
      offer a theoretical explanation for a problem which is important for both doctors
      and patients.

PMID- 1389428
TI  - Patient access to general practitioners by telephone: the doctor's view.
AB  - Few general practitioners have extensive daytime telephone contacts with
      patients. Forty nine general practitioners responding to a postal survey who
      reported handling a mean of nine or more calls a day were interviewed about their
      experiences. The nature of telephone contacts with patients and the
      organizational strategies employed to minimize disruption to surgeries were
      explored. Views on the rewards and frustrations of being accessible by telephone
      and its impact on other aspects of workload were also sought. Recommendations are
      made for practices contemplating extending telephone access for patients.

PMID- 1389429
TI  - Evaluation of the use and usefulness of telephone consultations in one general
      practice.
AB  - In one practice with 14,000 patients an advice line was set aside at designated
      times to enable patients to speak directly to a doctor on the telephone. The aim
      of this study was to determine who used the line, why they called, the conditions
      callers presented with, the action taken by the doctor and whether patients and
      doctors thought the service was a good idea. A total of 277 calls were made
      during the five month study period. Responses to a questionnaire were received
      from doctors for all 277 calls and from 152 patients. It was found that most
      calls lasted about three minutes. Most of the callers (59%) were known to the
      doctor taking the call. Users of the advice line were most likely to be women,
      married people and people with children. Equal numbers of calls were received
      about new and existing problems. The most frequent reason for calling was to
      obtain the result of a test (21% of calls). The most frequent diagnosis by the
      doctors was chronic complaints for which the patient was already receiving
      treatment (19%). The data from patients and doctors were similar. In 30% of cases
      callers were advised to take medicine, mostly a prescription to be collected
      (16%), while a few callers received a home visit (7%). Doctors thought they
      provided reassurance in 26% of cases while callers thought they had received
      reassurance in 43% of cases. If the advice line had not been available three
      quarters of the respondents would have made an appointment and 13% would have
      asked the doctor to make a home visit.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389430
TI  - Postgraduate education allowance: general practitioners' attendance at courses
      outwith their region.
AB  - A study was undertaken to investigate the number of doctors attending
      postgraduate education courses outwith their own region. During the one year
      study period general practitioners from the west of Scotland obtained 2262.0 half
      day sessions accredited for the postgraduate education allowance from 335
      different courses outwith their region and 10 different distance learning
      programmes. Four hundred and thirteen doctors from the west of Scotland region
      (22.6%) attended courses in other areas and 85 doctors (4.6%) participated in
      258.6 half-days of distance learning. More than half of the education sessions
      (56.0%) were in the category of disease management. Sixty four doctors (3.5%)
      attended 10 or more half-day sessions outwith their region. Almost half the
      courses were in England and 32.5% of courses were in south east Scotland. Over
      the same period 122 doctors outwith the area attended 263 different courses in
      the west of Scotland region. Despite concern regarding the removal of travel and
      subsistence contributions for postgraduate education activities, general
      practitioners are attending education courses outwith their region.

PMID- 1389431
TI  - Attitudes to and perceived use of health care services among Asian and non-Asian
      patients in Leicester.
AB  - A random sample of 449 Asian patients and 447 non-Asian patients were interviewed
      at home in their preferred language using a personally administered questionnaire
      comparing attitudes to and perceived use of health care services in Leicester.
      The overall response rate was 89.6%. There were differences in the responses of
      the Asian and non-Asian populations. With respect to communication, language as a
      barrier appears to be a diminishing problem among Asian patients in Leicester.
      However, Asian patients reported finding it more difficult to gain access to
      their general practitioners than non-Asian patients. More Asian than non-Asian
      patients would have preferred direct access to consultants and most respondents
      from both populations felt they should be able to request a hospital opinion from
      their general practitioner. More Asian patients disliked management of illness by
      telephone than non-Asian patients, the latter feeling that telephone advice could
      save them a trip to the surgery, or their general practitioner a home visit.
      However, both groups regarded home visiting as essential. Asian patients disliked
      deputizing services more than non-Asian patients, and there was some support for
      24 hour surgeries, particularly among the Asian population, with doctors working
      in shifts. As Asian patients appear to differ from non-Asian patients with
      respect to attitudes and perceived need for health care services, this type of
      survey may form the basis for the more rational planning of health care delivery
      to ethnic minority patients in the future.

PMID- 1389432
TI  - Is there still a role for benzodiazepines in general practice?
AB  - Opinion on benzodiazepines has moved from optimism after their entry onto the
      market to disillusionment over their potential for dependence. Legal proceedings
      against manufacturers of benzodiazepines, health authorities and doctors will be
      taking place this year. Nonetheless, just over 18 million prescriptions for
      benzodiazepines were issued in 1990, most of which came from general practice. Is
      there any role left for this group of drugs? This review addresses the issues of
      dependence on an withdrawal from benzodiazepines and weighs up the evidence for
      their present vilification.

PMID- 1389433
TI  - William Pickles Lecture 1992. What our practices teach us.

PMID- 1389434
TI  - The Royal College of General Practitioners: its growth and influence over the
      past 40 years.

PMID- 1389435
TI  - GPs' opinions on the use of an interim discharge summary for psychiatric
      inpatients.

PMID- 1389436
TI  - Envenomation by the lesser weever fish.

PMID- 1389437
TI  - Computerized health information.

PMID- 1389438
TI  - Detection of colorectal cancer.

PMID- 1389439
TI  - The health of the nation from a local perspective.

PMID- 1389440
TI  - Vocational training.

PMID- 1389441
TI  - Preventive care of elderly people.

PMID- 1389442
TI  - Sudden infant death syndrome.

PMID- 1389443
TI  - Night-time fears in children.

PMID- 1389444
TI  - The influence of antisocial toys on children's behaviour and attitudes.

PMID- 1389445
TI  - The epidemiology and prevention of Haemophilus influenzae infections in
      Australian aboriginal children.

PMID- 1389446
TI  - State of infant around birth: do we know what we are talking about?

PMID- 1389447
TI  - Stepping out: the emergence of research in community paediatrics.

PMID- 1389449
TI  - Factors influencing parental compliance following school entry health screening.
AB  - This study investigated the factors influencing parental action on behalf of
      their child following a school entry health screening failure. It was predicted
      that compliance with recommendations to seek further assessment would be related
      to the screening process variables and the number of barriers to compliance
      parents faced and that these barriers, and hence compliance, would be influenced
      by the socio-economic status of the family. It was also expected that when
      schools were differentiated on adversity factors, the type of school attended
      would be related to compliance. Results from a sample of parents (n = 1231)
      showed that the parental non-compliance rate to a referral of their child for
      further assessment following health screening was 26.1%. Non-compliance was
      related to both screening process knowledge and satisfaction and the type of
      barriers to compliance parents experienced. Although the type and number of
      barriers experienced by parents was related to socio-economic status, the results
      of correlational and discriminant function analyses indicated that the barriers
      most strongly related to compliance (e.g. partner's views, time pressure, more
      serious problems to worry about) were not related to socio-economic status nor
      type of school attended. These findings provide valuable information for child
      health service providers as well as those involved in policy making and planning
      in the general area of community health services.

PMID- 1389448
TI  - Using a computer database to record and evaluate a school screening service.
AB  - School screening has been taking place in New South Wales since 1907. The need
      for better monitoring of the school health service to determine the outcome of
      the screening process has been advocated frequently. This paper reports on the
      development of a computerized surveillance system which allows school screening
      to be evaluated on an ongoing basis. The results of the first year's use of the
      programme on a study population of children first screened in 1989 in a northern
      metropolitan area of Sydney demonstrate that the system is practical and
      effective when used by people with little or no prior computer knowledge. It
      plays a role in both improving follow-up of the screening process and the
      assessment of the service. The prevalence rate of new defects found was four per
      100 children screened. Issues raised about the screening process from the data
      collected are also discussed.

PMID- 1389450
TI  - Searches for matched and closely matched related and unrelated bone marrow donors
      undertaken in a single paediatric unit.
AB  - Information regarding the likelihood of finding suitable marrow donors is
      limited. In order to determine this potential, all patients who received their
      primary care at a single paediatric institution over a 9 year period and in whom
      tissue typing studies were initiated are reviewed. Forty-five (31.3%) of 144
      patients had a sibling who was human leucocyte antigen (HLA) identical. A further
      16 (11.2%) patients had immediate or more distant relatives who were either HLA
      identical (2.7%) or matched for five of six HLA antigens (8.3%). The possibility
      that a parent was closely matched with the patient was suggestive from the typing
      of siblings alone in only half the cases. Unrelated HLA matched donors were
      identified in four (27%) of 17 bone marrow bank searches. Overall, a potential
      related donor was identified within the family for 42% of patients and this
      figure rose to 45% when successful marrow bank searches were included. It can be
      concluded that initial typing should include both the parents and siblings. If a
      suitable donor is not found then an extended family and/or bone marrow bank
      search will identify additional suitable donors in a significant number of
      families.

PMID- 1389451
TI  - Health problems and health checks in school-aged children with Down syndrome.
AB  - A survey by parent questionnaire and interview was carried out to determine the
      frequency of health problems in 204 children with Down syndrome. Seventy-two
      children (35.3%) had a congenital heart defect. Refraction had been performed on
      196 and 68 (34.6%) of these had a refractive error. A diagnosis of 'glue ear' had
      been made in 112 (54.9%) and in 12 (11%) of these permanent hearing loss was
      present. Significant ill-health over the previous 12 months consisted of cardiac
      failure (two children), more than three upper respiratory tract infections (24
      children), bronchitis (eight children), pneumonia (two children) and asthma
      (seven children). A neck X-ray had been performed in 172 (84.3%) and had
      demonstrated the presence of atlanto-axial instability in 12 (7%) of these. One
      hundred and thirty-two (64.7%) of the children had been tested for hypothyroidism
      in the previous 18 months and this had been found in four (3%) of these children.
      The implications of these and other findings are discussed in relation to
      parental counselling and planning of routine health checks.

PMID- 1389452
TI  - Motorcycling attitudes and behaviours. II. 14 and 15 year old adolescents.
AB  - Of 846 adolescents interviewed near their 15th birthday, 51% could drive a
      motorcycle. A further 13% intended to learn. Drivers reported friends (mean age
      16.5 years) as the most common source of instruction. Forty-four per cent of
      drivers and 69% of intending learners planned to apply for licences. Thirty-five
      per cent of the sample had driven or ridden as passengers on a motorcycle on-road
      in the past year and 85% of these had worn a helmet on the last occasion. The
      commonest cause of injuries to motorcyclists resulting in hospitalization (lower
      limb injury) was correctly identified by 52% of the sample. Fear of injury was
      the reason given for not learning to ride by 55% of confirmed non-drivers.
      Fifteen medically treated motorcycling injuries were reported for a 2-year recall
      period. Females reported significantly less exposure and less use of protective
      clothing than males. The issues of initiation, training, constraints on use and
      preventive strategies are discussed.

PMID- 1389453
TI  - The role of a saliva control clinic in the management of drooling.
AB  - This paper describes a saliva control clinic which has been established at the
      Royal Children's Hospital, Melbourne. A team involving two speech pathologists, a
      paediatrician, a plastic surgeon and a dentist has assessed and managed 68 young
      people over a period of 2 years. Treatment options have included behavioural
      programmes, trial of oral appliances, medication and surgery. This
      multidisciplinary approach has been useful in developing assessment techniques
      and formulating recommendations.

PMID- 1389455
TI  - Citrobacter freundii septic arthritis.
AB  - Septic arthritis in an 8 month old infant due to Citrobacter freundii was treated
      successfully with a third generation cephalosporin. Infections due to Citrobacter
      are uncommon in this age group and are almost unknown as a cause of septic
      arthritis.

PMID- 1389454
TI  - The association of thyroid dyshormonogenesis and deafness (Pendred syndrome):
      experience of the Victorian Neonatal Thyroid Screening Programme.
AB  - Between 1977 and 1989, the Victorian Neonatal Thyroid Screening Programme
      detected five subjects with thyroid dyshormonogenesis and sensorineural deafness.
      These patients have been diagnosed as having Pendred syndrome. In two of the
      children, thyroid function tests which were initially abnormal at birth returned
      to normal spontaneously without treatment. However, hypothyroidism subsequently
      recurred and the children required thyroxine therapy. These two children could
      have been mistakenly diagnosed as having transient hypothyroidism. The detection
      of five patients with Pendred syndrome illustrates the importance of audiological
      assessment in all babies with thyroid dyshormonogenesis in whom there is
      increased uptake of isotope on thyroid scanning. In our experience, hearing loss
      in patients with Pendred syndrome may be progressive over time, so that repeated
      audiological assessments are necessary.

PMID- 1389456
TI  - Case studies in adolescent deliberate self-harm.
AB  - Four adolescents admitted to a general paediatric ward at a teaching hospital
      with deliberate self-harm were reviewed. Their initial psychosocial assessment
      was noted together with their subsequent course 12 months later. Despite an
      extensive assessment by a multidisciplinary team during the initial admission,
      follow-up 12 months later revealed that each subject appeared to have ongoing
      problems. This outcome raised doubts as to the appropriateness and effectiveness
      of a prolonged hospital admission in their initial assessment. The difficulties
      encountered with their management are highlighted.

PMID- 1389457
TI  - Cost analysis of extremely low birthweight infants: an update.

PMID- 1389458
TI  - Review of the first decade of the Annual Review of Nursing Research.

PMID- 1389459
TI  - Alcohol and drug abuse in nurses.

PMID- 1389460
TI  - Childhood and adolescent bereavement.

PMID- 1389461
TI  - Nursing centers.

PMID- 1389462
TI  - Nursing administration education.

PMID- 1389463
TI  - The staff nurse role.

PMID- 1389464
TI  - International nursing research.

PMID- 1389465
TI  - Urinary incontinence in older adults.

PMID- 1389466
TI  - Diabetes mellitus.

PMID- 1389467
TI  - Battered women and their children.

PMID- 1389469
TI  - Vascular damage and tumour response.

PMID- 1389468
TI  - Chronic mental illness.

PMID- 1389470
TI  - Dilemmas in the development of cytoxic drug analogues.

PMID- 1389471
TI  - Breast awareness: what do we really mean?

PMID- 1389472
TI  - DT-diaphorase activity correlates with sensitivity to the indoloquinone EO9 in
      mouse and human colon carcinomas.
AB  - The indoloquinone EO9 exhibits promising in vitro and in vivo antitumour
      activity. EO9 is metabolised to DNA damaging species by DT-diaphorase in vitro.
      In the present study DT-diaphorase specific activity was 16 fold higher in the
      mouse adenocarcinoma MAC 16, a tumour which is quite responsive to EO9 in vivo,
      compared with levels in the more resistant mouse adenocarcinoma MAC 26. This
      order of responsiveness is the reverse of that seen with the most active of the
      clinically used agents in these tumours [chloroethylnitrosoureas and 5
      fluorouracil (5-FU)]. In addition, when the in vitro sensitivity of two human
      colon carcinoma cell lines was compared, EO9 was 15-30 fold more active in the DT
      diaphorase rich HT29 line than in the enzyme-deficient BE cell line counterpart.
      These results are consistent with the hypothesis that DT-diaphorase expression
      may be a major determinant of the sensitivity of tumours to EO9. This should be
      considered in the clinical development of the drug.

PMID- 1389473
TI  - Differences in the level of DNA double-strand breaks in human tumour cell lines
      following low dose-rate irradiation.
AB  - It is now well accepted that differences exist in the intrinsic radiosensitivity
      of human tumour cells although the molecular basis of this is still unclear.
      Current evidence suggests that of the lesions induced in DNA by ionising
      radiation, double-strand breaks (DSB) are the most closely linked to cell death.
      In this study, levels of DSB were measured by neutral filter elution under
      conditions of both repair inhibition and maximum recovery and compared with
      clonogenic survival curves for high (HDR) and low dose-rate (LDR) irradiation in
      human carcinoma lines of differing radiosensitivity. Four human lung carcinoma
      lines were used, two small-cell (SCLC; HC12 and HX149) and two non-small cell
      lines (NSCLC; HX147A7 and HX148G7). Cell survival was measured by soft agar and
      monolayer colony-forming assays as appropriate and a large variation in
      sensitivity of the cell lines was seen (alpha values of 0.06 to 0.56 Gy-1). We
      have previously reported that the damage induced at high dose rate does vary in
      these cell lines but not in a way which correlates with their cell survival
      response [5]. Following irradiation to 15 Gy at low dose rate essentially no DSBs
      were detected in any of the four lines but at 70 Gy the more sensitive SCLC
      showed more residual damage than in the more radioresistant NSCLC lines. The
      prime determinant of the difference between the LDR and HDR damage curves is
      likely to be repair occurring during irradiation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1389474
TI  - No correlation between ras, c-myc and c-jun proto-oncogene expression and
      prognosis in advanced carcinoma of cervix.
AB  - 55 patients suffering from stage III or IV carcinoma of cervix were treated with
      two pulses of neo-adjuvant chemotherapy prior to radical radiotherapy. 51%
      (26/51) had a partial response. The initial response to chemotherapy is
      associated with significantly better long-term survival. The 3-year survival of
      chemotherapy responders is 62% against 21% for non-responders (P = 0.009 log-rank
      test). To detect possible differences in oncogene expression in biopsy specimens
      taken from responding and non-responding patients, paraffin-fixed material was
      immunocytochemically stained for the expression of the protein products of ras, c
      myc and c-jun proto-oncogenes. The frequency of oncogene expression was ras
      80.4%, c-myc 45.1% and c-jun 39.2%. There was no statistically significant
      association between oncogene expression, time to local recurrence or development
      of metastases or survival.

PMID- 1389475
TI  - Screening of new anticancer agents in vitro using panels of human cell lines
      derived from non-seminomatous germ cell tumours and transitional cell carcinomas
      of the bladder.
AB  - Metastatic testis tumours are cured in over 80% of patients using combination
      chemotherapy, and this hypersensitivity is retained by the cells in vitro. To
      determine whether differential toxicity to testis tumour cells is useful in the
      screening of novel anticancer agents, we compared the toxicities of 12 compounds
      against panels of human bladder and testis tumour cell lines using a clonogenic
      assay. The compounds had screened negative against P388 in vivo, and had been
      retested using the human tumour colony forming assay (HTCFA) and in selected
      cases against human tumour xenografts. NSC 339004, chloroquinoxaline
      sulphonamide, was 7-fold more toxic to testis tumour than bladder cancer cells,
      comparing the mean of the concentrations reducing colony-forming ability by 70%.
      This was the only one of the compounds selected by the HTCFA shown to have
      clinical activity. Compound R was selectively toxic to the bladder cancer cells,
      and might be of value as an intravesical agent. These data indicate that panels
      of testis and bladder cancer cell lines might be a useful addition to the disease
      oriented screening programme.

PMID- 1389476
TI  - Downmodulation of c-myc expression by interferon gamma and tumour necrosis factor
      alpha precedes growth arrest in human melanoma cells.
AB  - After in vitro incubation of melanoma tumour cells Cmel453A with either
      recombinant interferon gamma (rIFN-gamma) or tumour necrosis factor alpha (rTNF
      alpha) a dose-dependent inhibition of cell growth occurred; when both cytokines
      were added, a synergistic action was observed. Inhibition of DNA synthesis, as
      measured by [3H] thymidine incorporation, occurred after 6 h of incubation with
      rIFN-gamma or rTNF-alpha, and this action was potentiated when the two cytokines
      were applied simultaneously. Within 1 h, the level of c-myc mRNA in tumour cells
      had already decreased by, respectively, 60% (S.D. 7) and 25% (S.D. 7); the
      combined addition of the cytokines resulted in a greater reduction of c-myc mRNA
      than by each cytokine alone. Downregulation of c-myc expression is an early
      event, occurring hours before the actual inhibition of outgrowth. Thus, in
      melanoma cells like Cmel with a high constitutive expression of the c-myc
      oncogene, the antiproliferative action of rIFN-gamma and rTNF-alpha may be
      mediated by an inhibition of the expression of c-myc.

PMID- 1389477
TI  - Flavone acetic acid induced changes in human endothelial permeability:
      potentiation by tumour-conditioned medium.
AB  - Flavone acetic acid (FAA) causes significant regression of larger established
      tumours in murine in vivo systems. This in vivo effect of FAA has been shown to
      include a vascular component. In an effort to elucidate the mechanism of action
      of FAA, we have studied the effects of FAA on the permeability of human
      endothelium in vitro. Monolayers of human umbilical vein endothelial cells
      (HUVEC) grown on polycarbonate filters were incubated in 1 mg/ml FAA for 120 min
      at 37 degrees C. During the first 60 min, there was a 6-8-fold increase in
      permeability; this was followed by a return to control levels even in the
      continued presence of FAA. In contrast, in the presence of tumour conditioned
      medium, FAA caused a rapid 6-fold increase in permeability which did not
      subsequently return to control levels. The permeability changes which occurred
      under the latter conditions were accompanied by a rapid contraction of the
      cytoskeleton. The permeability of monolayers of human melanoma cells was
      unaffected by FAA.

PMID- 1389478
TI  - Pharmacological purging of syngeneic bone marrow ex vivo: effect of treatment
      with doxorubicin and lonidamine on normal and leukaemic cells of DBA/2 mice.
AB  - The in vivo effect of in vitro treatment with doxorubicin plus lonidamine on
      normal and leukaemic cells was investigated in a mouse model of syngeneic bone
      marrow transplantation. Different numbers of L5178Y tumour cells or normal bone
      marrow cells alone, or mixtures of bone marrow and leukaemic cells were incubated
      with doxorubicin (0.25, 0.5, 0.75, 1 microgram/ml) and/or lonidamine (50
      micrograms/ml) and reinfused in DBA/2 mice. Lonidamine potentiated the cytotoxic
      effect of doxorubicin dependent on doxorubicin dosage and tumour cell
      concentration. Survival after injection of 10(4) in vitro-treated tumour cells
      was 42% for doxorubicin 0.75 micrograms/ml alone versus 100% for the combination
      with lonidamine and 50% for doxorubicin 1 microgram/ml alone versus 100%
      combination. Reinfusion of normal bone marrow incubated with doxorubicin alone or
      in combination with lonidamine in lethally irradiated mice did not occur in 12
      14% of mice injected, indicating that the repopulating ability of stem cells was
      spared. These data suggest the potential usefulness of lonidamine in ex vivo
      purging of bone marrow before autologous bone marrow transplants in haemopoietic
      malignancies.

PMID- 1389479
TI  - Anti-neoplastic action of peritoneal macrophages following oral administration of
      ether analogues of lysophospholipids.
AB  - Inflamed lesions of normal and cancerous tissues induce activation of
      phospholipase A in plasma membranes resulting in the release of various
      decomposed products of membranous lipids. Oral administration in mice of
      dodecylglycerol (DDG), a synthetic alkyglycerol, and an alkyl ether analogue of
      lysophospholipids, 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (ET-18
      OCH3-choline) efficiently activated peritoneal macrophages for enhanced Fc
      mediated (fragment crystallisable) ingestion of red blood cells and direct
      cytotoxic action on retinoblastoma tumour cells. The activated macrophages not
      only inhibited tumour cell growth, but also markedly induced cytolysis of tumour
      cells. The antitumour capability of the macrophages was substantiated by luminol
      enhanced chemiluminescence. These findings suggest that dodecylglycerol and ET-18
      OCH3-choline administered orally retain their ability to induce a high level of
      macrophage activation and tumour cytotoxicity, just as occurs with
      intraperitoneal administration. Thus, these compounds have potential practical
      application in chemotherapy and immunotherapy of the tumour, which could be
      accomplished by simple oral rather than parenteral administration.

PMID- 1389480
TI  - Cell proliferation kinetics of human gastric carcinoma: an immunohistochemical
      study with a monoclonal antibody against DNA polymerase-alpha.
AB  - Cell proliferation kinetics of human gastric carcinoma were studied
      immunohistochemically using a monoclonal antibody against DNA polymerase-alpha
      (Pol-alpha). The distribution patterns and percentages of proliferative cells
      were examined in cases with various histological types of gastric carcinoma and
      compared with those of normal epithelium of the gastric foveolae. Pol-alpha
      positive epithelial cells were localised at the isthmus of the normal foveola,
      while Pol-alpha-positive cancer cells were distributed irregularly in the cancer
      nests. The percentage of Pol-alpha-positive cells (%PPC) was significantly higher
      in the carcinoma [mean (S.D.) 41.6 (12.9)%] than in the normal foveola [24.8
      (6.4)%] (P < 0.01). Also, the intestinal-type carcinoma showed a relatively
      higher %PPC [44.9 (12.0)%] than the diffuse type [36.2 (15.1)%] (P<0.05), and the
      %PPC of signet ring cell carcinoma was extremely low [7.3 (2.2)%] (P< 0.01). Pol
      alpha-positive cancer cells were observed most abundantly in the lamina propria
      of the mucosa. They decreased in number with the depth of cancer infiltration
      down to the subserosa.

PMID- 1389481
TI  - High-dose rapid schedule chemotherapy for disseminated neuroblastoma.
AB  - In a high-dose schedule for disseminated neuroblastoma, eight courses of
      chemotherapy were administered every 10 days, regardless of myelosuppression, to
      eradicate tumour cells rapidly and reduce emergence of drug-resistant clones.
      Relatively non-myelotoxic vincristine and cisplatin were alternated with high
      dose cisplatin-etoposide and cyclophosphamide-etoposide. Of 12 evaluable
      patients, there were 1 complete (CR), 3 very good partial (VGPR), 5 partial (PR)
      and 3 mixed responses (MR) 100 days after starting treatment. 6 out of 9 achieved
      a bone marrow CR at 40 days. 9 of 11 primary tumours were completely resected,
      after which 4 patients had CR, 3 VGPR (bone scan alone being abnormal), 4 PR and
      1 mixed response (MR). Myelotoxicity was the major adverse effect. The only death
      was due to fungal infection. Clinically important renal dysfunction occurred in 3
      patients. 4 had convulsions and 4 temporary hypertension. This schedule produced
      a rapid response and its toxicity, though serious, was manageable. Further
      evaluation is warranted.

PMID- 1389482
TI  - Heterogeneity of tumour necrosis factor production in renal cell carcinoma.
AB  - Endogenous tumour necrosis factor (TNF) production was investigated by in situ
      hybridisation and immunohistochemistry in 8 renal cell carcinoma (RCC) patients
      at different stages of disease. Analysis of frozen sections of tumour biopsy
      specimens revealed variable degrees of macrophage infiltration and great
      heterogeneity in TNF gene expression. Two metastatic tumours investigated showed
      abundant TNF protein production and marked macrophage infiltration. Based on
      morphological criteria, these TNF-positive cells most likely belong to the
      macrophage lineage. Two years after nephrectomy the individual survival time was
      recorded; however, the small numbers did not yet allow any correlation of TNF
      production to the clinical course of disease. Further studies will be required to
      eventually reveal the role of TNF in renal cell carcinoma development.

PMID- 1389483
TI  - Early assessment of a new anticancer drug analogue--are the historical
      comparisons obsolete? The French experience with pirarubicin.
AB  - Data of all phase II studies of pirarubicin (THP-doxorubicin) have been analysed
      for toxicity or activity in breast cancer and compared with published reports on
      doxorubicin, epirubicin or mitoxantrone used as single drugs. A graph of the 95%
      confidence intervals for each event was used. The results suggest that
      pirarubicin is as effective as other intercalating drugs in breast cancer and
      grossly better tolerated than doxorubicin, especially alopecia and cumulative
      cardiotoxicity. The equimyelotoxic doses of each drug were also estimated. The
      methodology and the validity of such historical comparisons is discussed: they
      cannot replace prospective randomised phase III studies, and do not allow
      definitive conclusions. However, most comparative trials of anticancer drug
      analogues cannot answer the right questions because their objectives are not
      adequate (especially for equiefficacy). But early evaluation by historical
      comparisons can help the conception of phase III studies.

PMID- 1389484
TI  - Prognostic value of progesterone receptor after long-term follow-up in primary
      breast cancer.
AB  - In a previous study of a series of 105 patients with primary breast cancer we
      found that the progesterone receptor (PgR) status was an important prognostic
      factor for early recurrences. 95 patients from the same series were followed-up
      for a median of 9.5 years and reassessed for the prognostic value of PgR status
      by univariate and multivariate statistical methods. In univariate analysis, the
      disease-free interval was only related to the lymph-node status. For overall
      survival, PgR and combined PgR-ER (oestradiol receptor) status had a prognostic
      value (P = 0.035 and 0.05, respectively). Moreover, PgR status was found to be
      discriminant for the survival of the node-negative patients (P = 0.017). In
      multivariate analysis, ER and PgR status were not significant, indicating that
      receptor status is not a powerful predictor of the course of breast cancer.

PMID- 1389485
TI  - The assessment of sexual function in cancer patients.
AB  - The sexual function of cancer patients may be compromised by their disease or
      treatment. This is infrequently assessed as an outcome variable and
      methodological differences between reported studies make comparison difficult.
      Where sexual function is being assessed as one dimension of a more comprehensive
      assessment of quality of life, a single item concerned with frequency of
      intercourse or satisfaction may be sufficient, but many studies require more
      detailed information. Methods developed for clinical assessment of sexual
      dysfunction are generally too long and detailed for this purpose. The best
      developed scales for cancer patients are embedded in lengthy and expensive
      questionnaires. A pool of items can be identified from which a scale could be
      derived to assess the relevant aspects of sexual experience. The development of
      an appropriate and psychometrically sound scale is now required to encourage
      greater consideration of the impact of disease and treatment on cancer patients'
      sexual function.

PMID- 1389487
TI  - Neuron-specific enolase as a prognostic factor in metastatic malignant melanoma.
AB  - Serum neuron-specific enolase (NSE) was measured in 63 patients with metastatic
      malignant melanoma. 20 patients (32%) had elevated serum NSE (> 10 micrograms/l)
      before the start of treatment. Another 13 patients (21%) developed pathological
      NSE values during the course of the disease. In many patients, elevated NSE was
      related to a large tumour burden, and a gradual rise in serum NSE indicated
      disease progression. Patients with elevated pretreatment NSE had a median
      survival time of 3 months compared with 12 months for those with normal
      pretreatment NSE values. NSE thus proved to be a useful prognostic factor in
      metastatic malignant melanoma.

PMID- 1389486
TI  - Immunostaining of cathepsin D in breast cancer: quantification by computerised
      image analysis and correlation with cytosolic assay.
AB  - Cathepsin-D (cath-D) was quantified in 34 breast cancer specimens by
      immunohistochemical staining of frozen sections with a computer image analysis
      and the results were compared with the corresponding cytosolic assay. Cath-D
      concentrations varied from 0 to 420 arbitrary units (AU). Tumour cells were more
      intensely stained than peritumoral tissue with the D7E3 mouse monoclonal antibody
      than with rabbit polyclonal antibodies. There was a good correlation (r = 0.80)
      between cath-D values obtained either by immunohistochemistry with D7E3 antibody
      or by cytosolic immunoenzymatic assay. However, with a cut-off of 50 AU, 3 out of
      25 patients had higher immunohistochemical values and 2 had higher cytosolic
      values. Therefore, quantification of cath-D concentration in tissue section by
      immunostaining and a computerised image analyser, which is the only technique
      available for small tumours, should provide similar prognostic information to
      that obtained by assaying cath-D in the cytosol.

PMID- 1389488
TI  - Prognostic significance of pretreatment serum levels of squamous cell carcinoma
      antigen and CA 125 in cervical carcinoma.
AB  - Serum levels of squamous cell carcinoma antigen SCC, carcinoembryonic antigen CA
      125, and tissue polypeptide antigen were determined in 142 patients with primary
      cervical carcinoma, 60 patients with precancerous lesions and in 129 healthy
      women. With regard to elevated tumour marker levels, specificity ranged from
      94.6% to 97.7%. Sensitivity was highest (44.4%) for SCC. A stage relation was
      found for all tumour markers except for carcinoembryonic antigen. In stage Ib,
      SCC levels increased according to tumour volume. SCC, CA 125 or both markers were
      elevated in 7 of 8 patients with pelvic lymph node metastases compared with only
      17 of 58 patients with negative nodes (P = 0.005). In a multivariate analysis,
      pretreatment serum levels of SCC and CA 125 were found to be significantly
      related to patient survival, in addition to stage. In cervical SCC, the risk of a
      fatal outcome increased 16 times with SCC levels > or = 4.5 ng/ml, compared with
      SCC levels < or = 1.3 ng/ml. We conclude that pretreatment serum levels of SCC
      may be of value as an adjunct to clinical staging. In addition, serum
      determinations of SCC and CA 125 seem to be useful in predicting the risk of
      pelvic lymph node metastases and as prognostic risk factors for disease outcome.

PMID- 1389489
TI  - Care and costs for advanced cervical cancer.
AB  - The types, amounts and costs of hospital and home care in patients who died from
      cervical cancer are investigated, using both national data sources and hospital
      files. Our goal has been assessment of the savings on treatment and care of
      advanced cervical cancer resulting from cervical cancer screening. Hospital costs
      account for 70% of the total cost per patient of Dfl 29,200. The amount of
      hospital care decreases significantly with increasing age. The average number of
      days of hospitalisation per patient with advanced disease decreases from 62 days
      below age 50 to less than 10 days at age 70 and older. In-hospital medical
      procedures, home care and nursing home care account for 24, 22 and 8% of the
      costs, respectively. Mass screening programmes for cervical cancer will result in
      a reduction in both advanced disease and mortality. The potential savings
      compensate approximately 10% of the costs of screening.

PMID- 1389490
TI  - Recent changes in the surgical management of T1/2 breast cancer in England.
AB  - Following the results of a study undertaken in 1985, a second survey was
      undertaken to examine whether there had been any changes in England in the
      surgical management of patients with a T1/2/NOMO breast cancer. The major
      findings were that: (i) there was a significant increase in the number of
      surgeons who would undertake breast conservation surgery; (ii) there was a
      significant increase in the number of surgeons who would discuss breast
      reconstruction where mastectomy was the preferred form of treatment; (iii) that
      significantly more surgeons would offer the patient a choice of surgery when
      there was more than one surgical option; and (iv) that significantly more
      surgeons had access to a breast specialist nurse and/or a cancer counsellor.
      These changes are consistent with the recommendations of the 1986 King's Fund
      Consensus' Conference for breast cancer treatment.

PMID- 1389491
TI  - The influence of intramuscular 4-hydroxyandrostenedione on peripheral
      aromatisation in breast cancer patients.
AB  - The influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA) given
      intramuscularly on the peripheral aromatisation of androstenedione into oestrone
      was investigated in postmenopausal women with breast cancer and compared with the
      suppression of plasma oestradiol (E2). 7 patients were investigated before and
      during treatment on day 7, i.e. midway between two weekly injections. After an
      intravenous injection of [3H] androstenedione and [14C] oestrone, urine was
      collected for 96 h and the isotope ratio determined in the urinary oestrogen
      metabolites after isolation with high performance liquid chromatography. At 250
      mg, 4OHA inhibited aromatisation to [mean (S.D.)] 15.2 (5)% of baseline (P <
      0.002). There was significantly greater inhibition to 8.1 (2.7)% at 4OHA 500 mg
      (P < 0.01). Plasma E2 was reduced to 41.2 (14.1)% of baseline at 4OHA 250 mg with
      a further reduction to 32.7 (19.8)% at 500 mg (P < 0.05). These results confirm
      the dose-response relation previously established with plasma oestrogen
      measurements alone.

PMID- 1389492
TI  - Thyroid function 10-18 years after mantle field irradiation for Hodgkin's
      disease.
AB  - Thyroid function was measured in 81 patients who had been curatively irradiated
      on a mantle field for Hodgkin's disease 10-18 years ago. 47 patients (58%) had
      elevated levels of thyroid stimulating hormone, indicating hypofunction of the
      thyroid gland, compared with 4.6% of controls (hospital visitors) matched for age
      and sex. The mean free thyroxine index (FTI) was significantly lower in patients
      than in controls, but all FTI values were still normal. Age at the time of
      irradiation, sex, time since irradiation and administration of chemotherapy were
      not significant factors in the development of thyroid dysfunction. A life-long
      awareness of the possibility of insidiously developing myxedema in these patients
      is strongly advocated.

PMID- 1389493
TI  - Phase II study of interferon alfa-2a and dacarbazine in advanced melanoma.
      Biological Response Modifiers in Melanoma (BREMIM) Italian Cooperative Group.
AB  - In phase II, the tolerance and activity of dacarbazine and recombinant interferon
      alfa-2a (rIFN) was studied in 79 patients with metastatic melanoma. The regimen
      was well tolerated. Response rate was 25%, with 8% having a complete response.
      Response duration and survival after a follow-up of 39 months are reviewed. The
      mean durations of complete and partial responses are 13.7 months (range 1 to 31+)
      and 10 months (2 to 36+), respectively. Median time to progression is 3 months;
      median survival is 9 months. At present, 11% of treated patients are alive, thus
      addition of rIFN to dacarbazine may prolong response duration.

PMID- 1389494
TI  - Additional ecological evidence: lipids and breast cancer mortality among women
      aged 55 and over in China.
AB  - That dietary fat increases breast cancer risk has been strongly supported by
      international data collected among developed countries during the past few
      decades. Population aggregates with elevated lipid intake have tended to report
      elevated breast cancer incidence and mortality. This study is an ecological
      analysis of the association of various indicators of lipid intake with breast
      cancer mortality in 65 county-wide population aggregates in the People's Republic
      of China. Although the result is consistent with a positive association between
      lipid intake and breast cancer risk, the observed association is weaker than the
      association previously observed. This finding provides only modest support for
      the possibility of a diet-breast cancer link.

PMID- 1389495
TI  - Changes of lymphocyte subsets after local irradiation for early stage breast
      cancer and seminoma testis: long-term increase of activated (HLA-DR+) T cells and
      decrease of "naive" (CD4-CD45R) T lymphocytes.
AB  - Blood lymphocyte subsets of early breast cancer patients and of men with stage I
      seminoma of the testis were studied up to 6 years after radiotherapy. Similar
      results were obtained in the two patient groups. After a temporary decrease, the
      CD4-w29 or "memory" T cells recovered completely, while the CD4-45R or "naive" T
      cells remained decreased up to 6 years after irradiation. The number of CD8 T
      lymphocytes did not change during or after treatment. Because of the decrease of
      a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio
      decreased significantly after irradiation, and remained lower than before
      treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive
      CD4 and HLA-DR positive CD8 T cells ("activated" T cells) increased significantly
      after irradiation. The natural killer (NK) cells were not affected by treatment.
      We propose that the recovery of the CD4 cells is limited to the CD4-w29
      ("memory") population because of thymic dysfunction in older humans. The impact
      of the observed immune modulation on the low susceptibility for infections after
      local irradiation, and on putative antitumour immune responses is discussed.

PMID- 1389496
TI  - Cancer incidence in the province of Limburg, The Netherlands.

PMID- 1389497
TI  - Clinical oncology: case presentations from oncology centres--2. Carcinoid of the
      larynx.

PMID- 1389498
TI  - Cancer incidence registration and trends in the Department of Doubs, France.

PMID- 1389500
TI  - Toremifene for recurrent and advanced endometrial carcinoma.

PMID- 1389499
TI  - A new look at tumour immunology.

PMID- 1389501
TI  - Effects of recombinant human erythropoietin on clonogenic growth of primary human
      tumour specimens in vitro.

PMID- 1389502
TI  - Recombinant interleukin 2 for metastatic renal cell carcinoma in haemodialysis
      patients.

PMID- 1389503
TI  - CD10 expression in B-chronic lymphocytic leukaemia.

PMID- 1389504
TI  - Cancer in Oman.

PMID- 1389505
TI  - Cardiomyopathy after acute myocardial infarction after therapy with interleukin-2
      and tumour infiltrating lymphocytes.

PMID- 1389506
TI  - Malignant melanoma treated with natural interferons alfa and beta and DAV.

PMID- 1389507
TI  - Multiple myeloma in two sisters.

PMID- 1389508
TI  - The management of seminoma.

PMID- 1389509
TI  - Screening for colorectal cancer.

PMID- 1389510
TI  - Cathepsin D in breast cancer: a tissue marker associated with metastasis.

PMID- 1389511
TI  - Evidence for individual differences in the radiosensitivity of human skin.
AB  - Previously published clinical data have been re-analysed to investigate
      individual differences in the radiosensitivity of human skin. In the clinical
      studies, acute and late skin reactions were recorded for 254 breast cancer
      patients receiving radiotherapy to the internal mammary nodes following simple or
      modified radical mastectomy. Each patient was treated bilaterally with different
      fractionation schedules to the right and left fields. Patients were assigned
      prospectively to 10 different treatment groups of 11-35 patients each, with all
      patients in a group receiving the same pair of fractionation schedules to the
      right and left fields. In the present study, correlations between the skin
      reactions in the two treatment fields per patient were investigated. For each of
      three different endpoints--peak reflectance measure of erythema, peak acute skin
      reaction score, and a ranking measure of the progression rate of telangiectasia-
      significant correlations were found between the levels of skin injury to the
      right and left treatment fields of the patients in most treatment groups.
      Although there were correlations between the absorbed doses in the right and left
      fields, statistical analyses indicated that dose effects were not sufficient to
      explain fully the patient-to-patient differences in skin response. Thus, these
      data provide evidence for the existence of individual differences in the
      radiation response of human skin, both for early and late effects. Whether these
      differences are dominated by heterogeneity in intrinsic cell radiosensitivity or
      by other factors has yet to be determined. However, there was no clear evidence
      of a correlation between the acute and late endpoints, suggesting that the
      individual differences in radiosensitivity are not dominated by a common genetic
      component expressed equally in all cells.

PMID- 1389512
TI  - A randomised double-blind study of high-dose intravenous prochlorperazine versus
      high-dose metoclopramide as antiemetics for cancer chemotherapy.
AB  - High-dose prochlorperazine 0.8 mg/kg administered intravenously 30 min pre and 7
      h 30 min post the initial dose of emetogenic chemotherapy was compared to high
      dose metoclopramide 2 mg/kg over 20 min every 2 h for five doses starting 30 min
      prior to chemotherapy in a randomised, double-blind, parallel subjects design
      study. On the prochlorperazine arm intravenous dextrose placebos every 2 h
      maintained blinding. Complete suppression of vomiting occurred in 42% on
      metoclopramide (53% with non-cisplatin regimens) and 36% on prochlorperazine (52%
      with non-cisplatin-containing regimens) while major responses (2 or less vomits)
      occurred in 58% on metoclopramide and 54% on prochlorperazine. In patients who
      vomited after cisplatin, prochlorperazine achieved a significantly shorter
      duration of vomiting, a median of 5 h compared to 15 h on metoclopramide (P =
      0.03). The response rate to prochlorperazine for cisplatin-induced emesis between
      12 and 24 h was significantly better than for metoclopramide (prochlorperazine =
      0.02). Toxicities were equivalent except for significantly greater sedation and
      dry mouth on prochlorperazine. Extrapyramidal reactions were recorded equally on
      both arms but were only severe enough to stop treatment on metoclopramide. The
      metoclopramide regimen was five times as expensive as prochlorperazine. High-dose
      prochlorperazine is an active and cost-effective antiemetic.

PMID- 1389513
TI  - Elevation of ADP-ribosylation as an indicator of mononuclear leucocyte
      responsiveness in breast cancer patients treated with tamoxifen.
AB  - 82 women who had had surgery for removal of breast cancer were randomised during
      the primary care period before initiation of any chemotherapy or radiotherapy
      into two groups: no drug treatment (n = 40) and 20 mg tamoxifen per day for 2
      years (n = 42). Mononuclear leucocyte (MNL) fractions from blood samples were
      collected during the first 368 days of the study and ADP-ribosylation was
      quantified. Tamoxifen treatment resulted in a dose-duration increase in ADP
      ribosylation. This was true even after adjustment for covariates such as age,
      smoking habits, oestrogen use, menstruation and tumour size. These data suggest
      that part of the antitumour effects of tamoxifen treatment in vivo relates to an
      enhanced immune cell responsiveness, as indicated by the increased MNL ADP
      ribosylation.

PMID- 1389514
TI  - Fotemustine plus dacarbazine for malignant melanoma.
AB  - 119 patients with metastatic melanoma received fotemustine 100 mg/m2 on days 1
      and 8 and dacarbazine 250 mg/m2 on days 15-18. After a 5-week rest, fotemustine
      100 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 2-5 was given every 3-4
      weeks. 12 complete responses (11.6%) and 16 partial responses were observed in
      103 evaluable patients (response rate 27.2%). The median duration of response was
      21.5+ weeks (8+ to 53+). The response rate was 26.3% in CNS, 18.2% in visceral
      sites and 37.5% in non-visceral sites. The toxicity was mainly haematological:
      grade III-IV leukopenia in 27.4% and thrombocytopenia in 23.4%. The response rate
      was lower than that in 63 patients previously reported. The present series had a
      higher median age (54 vs. 40 years) without any differences in other population
      variables. However, activity on CNS metastases and on non-visceral sites was
      confirmed. Haematological toxicity was about 50% lower than that with fotemustine
      alone. Hence, this is an active outpatient regimen for metastatic melanoma,
      especially against cerebral and non-visceral metastases.

PMID- 1389515
TI  - Melphalan concentration and distribution in the tissues of tumour-bearing limbs
      treated by isolated limb perfusion.
AB  - Levels of melphalan (L-phenylalanine mustard) were measured in the tissues of
      tumour-bearing limbs treated by isolated limb perfusion (ILP). 41 samples of
      melanoma tissue, normal fat and skin were excised from 15 patients during ILP. A
      high performance liquid chromatography assay was used to measure melphalan
      concentrations. Levels of melphalan were higher in tumour than in fat (P < 0.01,
      Wilcoxon signed-ranks test), and not significantly different from levels in
      adjacent skin. In 2 cases there was significant regional toxicity in the treated
      limb, but this was not related to the levels of melphalan measured in the tissues
      of the limb. It is encouraging that the concentrations of melphalan which were
      achieved in large necrotic nodules by ILP were similar to those in well-perfused
      normal skin.

PMID- 1389516
TI  - Fotemustine plus dacarbazine in advanced stage III malignant melanoma.
AB  - 19 patients with advanced malignant melanoma were treated with fotemustine and
      dacarbazine. Data recorded and available for evaluation in all patients included
      clinical and histopathological parameters of the primary melanoma, blood
      chemistry, blood cell count, chest X-ray, ultrasound and bone scan for initial
      staging of the site of metastases and follow-up during treatment. Dosage was
      fotemustine 100 mg/m2 and dacarbazine 200 mg/m2 intravenously twice monthly on
      days 1 and 8, repeated for a maximum of six courses. There were two complete and
      three partial responses in 5/19 patients (26%), and 8 patients (42%) had stable
      disease. 6 (32%) patients had no response. Median length of complete and partial
      responses was 3.9 months, and that of stable disease 4.2 months. The main side
      effects were thrombocytopenia in 10 patients (53%) and nausea in 6 (32%); the
      nausea was easily suppressed by ondasetron. Thus, fotemustine-dacarbazine may be
      new treatment in advanced melanoma.

PMID- 1389517
TI  - Prognostic factors in patients with metastatic colorectal cancer receiving 5
      fluorouracil and folinic acid.
AB  - We have reported that 5-fluorouracil (5-FU) and folinic acid increased response
      rate and survival in patients with metastatic colorectal cancer. Now we have
      analysed prognostic factors for response, toxicity, survival and time to
      progression. The variables used for survival and response were treatment centre,
      treatment, age, sex, Eastern Cooperative Oncology Group (ECOG) performance status
      (PS), site of disease, previous radiotherapy, site of primary, disease-free
      interval, initial alkaline phosphatase (AP), albumin (A), lactate dehydrogenase
      (LDH) and aspartate aminotransferase (SGOT). The significant independent
      variables for survival were PS of 2 or more, initial albumin and SGOT, and
      treatment received, in order of importance. The relative risk of death when
      patients received 5-FU/folinic acid was 60% of that of patients receiving 5-FU
      alone. The variables predictive of response were treatment and PS. The variables
      used for analysis of toxicity were age, treatment centre, treatment, sex, tumour
      response, PS, number of courses, SGOT, AP and albumin. Treatment was found to be
      predictive of toxicity. Thus, baseline albumin and SGOT, and 5-FU/folinic acid
      treatment are significant determinants of survival, 5-FU/folinic acid and PS of 2
      or more are major determinants of response and no clinical parameter could be
      identified as a predictor of toxicity.

PMID- 1389518
TI  - Phase II trial of 5-fluorouracil and recombinant interferon alfa-2B in metastatic
      colorectal carcinoma.
AB  - Between February 1990 and April 1991, 59 previously untreated patients with
      progressive and/or symptomatic metastatic colorectal carcinoma were enrolled in a
      phase II study of 5-fluorouracil (5-FU) and interferon alfa-2b (IFN-alpha). 5-FU
      750 mg/m2/day was administered as continuous infusion for 5 days, then weekly in
      a dose of 750 mg/m2 as intravenous push injection starting on day 15. IFN-alpha 9
      MU was given subcutaneously three times a week. Treatment was given for a maximum
      of 6 months. 55 patients are evaluable for response and 51 for toxicity. 17
      patients (31%) achieved a partial remission, 15 (27%) had stable disease and 21
      patients (38%) had progressive disease. Median duration of remission was 5 months
      and median survival for all patients 10 months. Toxicity was important with two
      treatment-related deaths and severe leukopenia, fever, diarrhoea and mucositis in
      about one third of the patients. In our opinion, this regimen is effective but
      rather toxic in metastatic colorectal carcinoma.

PMID- 1389519
TI  - Randomised comparison of weekly bolus 5-fluorouracil with or without leucovorin
      in metastatic colorectal carcinoma.
AB  - 148 patients with advanced untreated colorectal cancer were randomised to receive
      a weekly bolus of 5-fluorouracil (5-FU) 600 mg/m2 alone, with or without
      leucovorin (LV) 500 mg/m2. 5-FU plus LV produced a higher response rate than 5-FU
      alone: 23% (5 complete response, 11 partial response) vs. 8% (2 complete
      response, 4 partial response) (P = 0.03) out of 70 and 72 evaluable patients,
      respectively. Median survival was 11 months in both groups and median time to
      progression was not significantly different (P = 0.08). The combined regimen was
      more toxic than 5-FU alone, as evidenced by (a) a higher percentage of grade 3-4
      diarrhoea, 19.5% vs. 8.5% (P = 0.045) and conjunctivitis, 26.5% vs. 5.6% (P =
      0.0025); (b) the recording of one toxic death in the combined arm; and (c) the
      reduction of the median dose intensity of 5-FU actually delivered during the
      first 2 months of treatment. We conclude that 5-FU plus LV at a price of a higher
      toxicity is more active than 5-FU alone without improving survival and
      progression-free survival.

PMID- 1389520
TI  - Phase II study of epirubicin sequential methotrexate and 5-fluorouracil for
      advanced colorectal cancer.
AB  - 91 patients with measurable metastatic colorectal carcinoma entered a phase II
      study. A three-drug schedule; epirubicin (20 mg/m2), sequential methotrexate (150
      mg/m2), 5-fluorouracil (600 mg/m2) with 1-h interval (EMF) with folinic acid
      rescue was given weekly three times followed by 2-3 weeks rest. 85 patients were
      evaluable for response. 5 patients (6%) experienced a complete response (CR), 20
      (23%) a partial response (PR), 31 (37%) had disease stabilisation (SD) and 29
      (34%) progressive disease (PD). The median survival time was 13.7 months in all
      patients (n = 91) and 14.0 months in those evaluable for response (n = 85). In
      patients with CR, PR, SD and PD the median survival time was 46.7, 19.8, 14.7 and
      8.7 months, respectively. The response rate was significantly (P < 0.05) higher
      in tumours originating from the colon (41%) than in those originating from the
      rectum (18%) and also significantly (P < 0.001) higher in non-symptomatic than in
      symptomatic patients, 40 vs. 4%, respectively. The treatment was fairly well
      tolerated as an outpatient regimen, the main dose-limiting side-effect being
      diarrhoea. Deaths for septic fever, which may be attributable to the treatment
      were encountered in 3 patients, all with progressive cancer. Further studies to
      disclose differences in response rate in subsets of patients are warranted.

PMID- 1389521
TI  - Postsurgical adjuvant chemotherapy with or without radiotherapy in women with
      breast cancer and positive axillary nodes: a South-Eastern Cancer Study Group
      (SEG) Trial.
AB  - In a prospective study of 622 women with breast cancer, those with one to three
      histologically positive axillary lymph nodes were randomised after mastectomy to
      receive cyclophosphamide 100 mg/m2 orally on days 1-14, methotrexate 40 mg/m2
      intravenously on days 1 and 8, and fluorouracil 600 mg/m2 intravenously on days 1
      and 8 every 28 days for six cycles (CMF x six), or for twelve cycles of the same
      chemotherapy (CMF x 12). Those with > or = four positive nodes were randomised to
      one of these two groups or to 5000 cGy of postmastectomy regional radiotherapy
      (RT) followed by six cycles of the same chemotherapy (RT + CMF x six). With about
      10 years median follow-up, there was no significant difference in survival or
      disease-free survival among the three groups. There was evidence of decreased
      locoregional recurrence in patients with > or = four nodes who received RT + CMF
      x six (relative risk 0.53, P = 0.067). Multivariate analysis indicated that the
      presence of > or = four positive nodes (negatively) and the percentage of ideal
      (full) dose of CMF received (positively) were the strongest factors predictive of
      survival. This study shows no advantage for 12 over six cycles of CMF
      chemotherapy in women with breast cancer and positive axillary nodes. There was a
      suggestion of decreased locoregional recurrence but no improvement in survival
      with radiotherapy for women with > or = four positive nodes.

PMID- 1389522
TI  - Radiation therapy in clinical stage I and II Hodgkin's disease. The Princess
      Margaret Hospital Lymphoma Group.
AB  - A review of the Princess Margaret Hospital experience over the last 20 years in
      treating clinically staged patients with stage I and II Hodgkin's disease was
      performed to analyse the impact of patient selection and extended field radiation
      on relapse and survival. Of the 878 patients with stage I and II Hodgkin's
      disease, 521 with clinical stages I and II received radiation alone as the
      initial treatment. The actuarial survival for all stage I and II patients was
      85.1% at 5 years and 76.2% at 10 years, and for clinically staged patients
      treated with radiation alone, 87.2 and 77.6%, respectively. The relapse-free rate
      (RFR) for all clinical stage I and II patients treated with radiotherapy (RT)
      alone was 70.1% at 5 years and 65.8% at 10 years. Significant prognostic factors
      for RFR and survival included age, stage and histology. In addition, the extent
      of radiation was identified as an independent prognostic factor for survival as
      well as for relapse. The RFR for those treated with involved field RT was 58.4%
      at 5 years and 50.5% at 10 years; for patients treated with mantle RT, 69.9 and
      65.6%, and those treated with extended field RT 77.4 and 75.8%, respectively. In
      a highly selected group of patients with no adverse features, i.e. with stages IA
      IIA, lymphocyte predominant or nodular sclerosis histology, erythrocyte
      sedimentation rate < 40, age < 50, no large mediastinal mass, and no E-lesions-
      the policy of mantle RT (M) and extended field RT (EF) produced comparable 5-year
      relapse-free rates (M, 84.9%; EF, 87.1%; P = 0.53). We conclude that a policy of
      treatment selection based upon clinicopathological prognostic factors and the use
      of extended field RT confers excellent results in the treatment of clinical stage
      I and II Hodgkin's disease.

PMID- 1389523
TI  - The EORTC trials for limited stage Hodgkin's disease. The EORTC Lymphoma
      Cooperative Group.

PMID- 1389524
TI  - Infradiaphragmatic Hodgkin's disease.

PMID- 1389525
TI  - Chemotherapy versus radiotherapy in early-stage Hodgkin's disease: evidence of a
      more difficult rescue for patients relapsed after chemotherapy.
AB  - Six cycles of mechloretamine, vincristine, procarbazine and prednisone (MOPP)
      chemotherapy were randomly compared with extended field radiotherapy (RT) in 89
      adult patients with pathological stage I-II A Hodgkin's disease (HD). 45 patients
      received RT and 44 were treated with MOPP. Complete remission (CR) was obtained
      in all patients in the RT group and in 40 of 44 in the MOPP group. 12 patients
      relapsed in both groups. 10 out of 44 patients treated with MOPP died of HD,
      compared with only 2 in the RT group. 3 more patients died in the MOPP group
      following the occurrence of second cancers. 11 out of the 12 (96%) patients
      relapsing after RT achieved a second CR, compared with 6 out of the 12 (50%)
      patients relapsing after MOPP. Analysis of the response rate with salvage
      treatment, shows that, of the 12 patients who relapsed after MOPP, the pattern of
      relapse might predict the likelihood of achieving a second CR, whereas in the RT
      group a second CR was achieved regardless of the characteristics of relapse.
      Survival probability for relapsing patients at 80 months calculated from relapse
      was 85% in the RT group and 15% in the MOPP group (P = 0.02). With a median
      follow-up of more than 8 years, the overall survival of patients was
      significantly better for RT compared with MOPP; 93 and 56%, respectively (P <
      0.001). On the basis of these results we conclude that, to date, RT alone remains
      the treatment of choice for adult patients with early-stage HD with favourable
      prognostic factors.

PMID- 1389526
TI  - A comparison of gallium-67 single photon emission computed tomography and
      computed tomography in mediastinal Hodgkin's disease.
AB  - The role of gallium-67 single photon emission computed tomography (Ga-67 SPECT)
      in the assessment of mediastinal Hodgkin's disease was evaluated prospectively.
      Ga-67 SPECT and computed tomography (CT) were compared and correlated with
      clinical findings at initial presentation in 30 patients, 6 weeks after
      treatment, and 6 months later in 20 of the 30 patients. At initial presentation,
      active disease was detected on both imaging modalities on all occasions. 6 weeks
      after treatment CT showed residual mediastinal abnormality in 7 patients, whereas
      Ga-67 SPECT showed abnormal mediastinal tracer uptake in 3 patients. 6 months
      later CT showed residual mediastinal abnormality in 5 patients whereas all the Ga
      67 SPECT studies were negative. Ga-67 SPECT imaging is a useful tool in assessing
      response to therapy in mediastinal Hodgkin's disease.

PMID- 1389527
TI  - An inter-observer and intra-observer variability study on the diagnosis of lymph
      node biopsy specimens.
AB  - One hundred lymph node biopsy specimens were examined on two separate occasions
      by seven pathologists differing in experience in lymphoreticular pathology.
      Neither history nor immunohistochemistry was provided and the study, therefore,
      focused on morphological interpretation alone. The participants evaluated each
      case using a constructed response form in which the confidence with which they
      entered each response was also entered. Agreement on various points, between
      pathologists, between the two rounds, and with the referring centre was assessed.
      Whilst there was a high level of agreement over a diagnosis of benign vs.
      malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably
      less agreement over both T vs. B cell phenotype and high vs. low grade. The lack
      of agreement over grade, an evaluation which is usually made independent of
      immunohistochemistry, is particularly important, because of the relevance to
      selection of treatment. Proliferation markers may be more appropriate
      determinants of treatment choice.

PMID- 1389528
TI  - Surgical treatment of myeloma of bone.
AB  - 33 patients treated operatively for plasma cell disease were analysed. There were
      21 men and 12 women with an average age of 54 years. There was an undefined bone
      tumour in 23 cases, and a pathologic fracture in 10 cases. In only 6 cases was
      the diagnosis known before the operation. The primary tumour localisations were:
      vertebral column in 13, pelvis in 7, femur in 6, humerus in 2, rib in 1, tibia in
      1, fibula in 1, scapula in 1 and olecranon in 1 case. 16 diagnostic biopsies were
      taken. Vertebral tumours were mainly evacuated or decompressed, combined with a
      stabilising procedure in 8 cases. A total of six endoprostheses, five to the
      femur and one to the humerus were performed. Two primarily wide resections, to
      the fibula and to the scapula were done. There were no locally recurring tumours
      during a mean follow-up time of 4 years and 2 months, and we conclude that
      operative and oncologic treatment is successful in providing the patient with a
      stable, pain-free locomotive system.

PMID- 1389529
TI  - Screening for psychiatric disorders in a lymphoma out-patient population.
AB  - The Hospital Anxiety and Depression Scale (HADS), a four-point, 14-item self
      assessment questionnaire, was tested as a screening method for psychiatric
      disorders in a sample of 117 Hodgkin's lymphoma and non-Hodgkin lymphoma
      consecutive out-patients. A receiver operating characteristic (ROC) analysis was
      performed, giving the relationship between the true positive rate (sensitivity)
      and the false positive rate (1--specificity). This makes it possible to choose an
      optimal cut-off score that takes into account the costs and benefits of treatment
      of psychiatric disorders (mainly adjustment, depressive and anxiety disorders) in
      a lymphoma out-patient population. A cut-off point of 10 gave 84% sensitivity and
      66% specificity. HADS appears in this study to be a well accepted, simple,
      sensitive and specific tool.

PMID- 1389530
TI  - High-dose and low-dose combined oral contraceptives: protection against
      epithelial ovarian cancer and the length of the protective effect. The WHO
      Collaborative Study of Neoplasia and Steroid Contraceptives.
AB  - The relations between use of high-dose and low-dose combined oral contraceptives
      and epithelial ovarian cancer were compared in an international hospital-based
      case-control study. 393 cases from seven countries were compared with 2561
      matched controls. The odds ratio (OR) was somewhat lower for women who used high
      dose oestrogen oral contraceptives (OR = 0.68) than for women who used low-dose
      preparations (OR = 0.81) although the difference could have occurred by chance.
      After controlling for time since last use, risk was slightly lower for long-term
      users of high-dose preparations than for long-term users of low-dose pills. Both
      high-dose and low-dose oral contraceptives protect against ovarian cancer, but
      the degree of protection may be slightly weaker for the newer, low-dose products.

PMID- 1389531
TI  - Doxorubicin weekly low dose administration: in vitro cytotoxicity generated by
      the typical pharmacokinetic profile.
AB  - The cytotoxic effects of prolonged exposure to low concentrations of doxorubicin
      or a doxorubicin bolus were examined in vitro on four human breast cancer cell
      lines to simulate the plasma concentration profile of weekly low-dose (WLD)
      doxorubicin in breast cancer patients. Cells were exposed to doxorubicin for
      various prolonged times (24, 72, 120 and 192 h) and with different drug
      concentrations (5, 10, 20, 50 and 80 nmol/l). In a series of parallel
      experiments, cell lines were placed in contact with the drug for short periods (1
      h) before prolonged exposure to doxorubicin; the concentrations of these pulses
      were 150, 250 and 350 nmol/l. A constant decrease in tritiated thymidine
      incorporation was noted as a function of the drug concentration and the duration
      of the cell contact with the drug. Interestingly the lowest concentrations (5-10
      nmol/l) produced marked cytotoxic effects. For equivalent concentration x time
      values, experiments including doxorubicin pulses resulted in greater cytotoxicity
      than continuous exposure alone, in a dose-related manner. This finding was
      related to differences in intracellular doxorubicin concentrations. Results
      suggest that the rather empirically designed WLD doxorubicin schedule can
      generate greater cytotoxic effects than continuous doxorubicin administration
      alone.

PMID- 1389532
TI  - Synergistic antiproliferative activity of tamoxifen and cisplatin on primary
      ovarian tumours.
AB  - We looked for the presence of the so-called type II oestrogen binding sites
      (EBS), in four oestrogen (ER) and progesterone (PR) receptor negative primary
      ovarian tumours. Moreover, the colony-forming assay was used to evaluate the
      response of ovarian cancer cells from these primary tumours to tamoxifen and
      cisplatin used alone or in combination. All tumours contained type II EBS, and
      tamoxifen was able to compete for [3H] oestradiol binding to these sites.
      Cisplatin and tamoxifen exhibited a dose-dependent inhibition of colony formation
      in a range of concentrations between 10 and 1000 micrograms/l and 37 and 3710
      micrograms/l, respectively. The combination of the two drugs resulted in a
      synergistic antiproliferative activity, with a potentiation up to and beyond 50
      fold. Our results show that in ovarian cancer tamoxifen interacts with type II
      EBS with an affinity consistent with the concentration effective both in
      inhibition of colony formation and in synergising cisplatin activity. Based on
      the experiments performed the action of tamoxifen on cell growth is independent
      of ER expression, and could be mediated by type II EBS. The possibility that the
      association of tamoxifen and cisplatin may result in an improved clinical
      response in ovarian cancer should be investigated.

PMID- 1389533
TI  - Growth stimulation of a human colorectal carcinoma cell line by interleukin-1 and
      -6 and antagonistic effects of transforming growth factor beta 1.
AB  - We analysed the effect of interleukin-1 (IL-1), IL-6 and transforming growth
      factor beta 1 (TGF beta 1) on the growth of a panel of eight colorectal carcinoma
      cell lines. IL-1 stimulated growth of two lines (LS411N and LS1034) up to 20-fold
      and IL-6 enhanced proliferation of LS1034 more than 5-fold. Both cytokines also
      augmented colony-formation of LS1034 in methylcellulose. Under both growth
      conditions IL-1 was the most potent stimulator. However, the addition of IL-6 to
      IL-1 synergistically enhanced proliferation of LS1034 in monolayer culture and
      additively augmented the number of colonies formed in methylcellulose.
      Furthermore, TGF beta 1 strongly reduced the growth rate of LS1034. Low amounts
      of TGF beta 1 markedly inhibited the response of LS1034 to IL-1 and totally
      abrogated proliferation induced by IL-6. We conclude that different cytokines can
      provide distinct signals for the regulation of growth of colorectal carcinoma
      cells.

PMID- 1389534
TI  - Tumour-infiltrating lymphocytes in cervical carcinoma.
AB  - Tumour-infiltrating lymphocytes from cervical carcinomas were cultivated in the
      presence of interleukin-2. The majority of bulk cultures were cytotoxic against
      K562, Mel 1 and Caski cells. CD8+ cells were the predominant subset in over 50%
      of cultures, with varying numbers of CD56+ and CD25+ cells. T cell clones were
      established from six tumour-infiltrating lymphocyte cultures and the majority
      exhibited non-MHC-restricted cytotoxicity. However, in one case cytotoxicity of
      several derived clones was limited to the autologous tumour and in another, to
      the autologous tumour and Caski cells. This study indicates that tumour
      infiltrating lymphocytes can be amplified and cloned from cervical carcinoma
      biopsies in the presence of rIL2. Although the predominant cytolytic function is
      non-MHC-restricted, low autotumour cytotoxicity can be demonstrated at the clonal
      level. The nature of the antigen(s) recognised by T cells on autologous cervical
      carcinoma cells in unknown; the candidacy of human papillomavirus-related
      products requires investigation.

PMID- 1389535
TI  - Phenotypic features of stromal cells in normal, premalignant and malignant
      conditions.

PMID- 1389536
TI  - The management of Hodgkin's disease in relapse after primary radiation therapy.
AB  - Approximately 20-25% of patients with stage I-II Hodgkin's disease treated
      initially with irradiation alone will experience a relapse of disease. Restaging
      at the time of relapse provides a useful prognostic indicator and may help in the
      selection of salvage therapy. Systemic treatment is indicated in nearly all
      patients. In the Stanford experience, 109 patients who relapsed were treated with
      MOPP (or MOPP-like chemotherapy) with or without local irradiation. The actuarial
      10-year survival and freedom from second relapse were both 57%. Important
      prognostic factors included 'relapse stage' (IA vs. II-IIIA vs. I-IIIB or IV) and
      type of salvage therapy (combined modality vs. chemotherapy alone). Important
      issues in management of these patients include the selection of chemotherapy
      agents, whether to incorporate localised irradiation, and the use of even more
      aggressive salvage treatment programs, such as autologous bone marrow
      transplantation, in selected patients with a very poor prognosis.

PMID- 1389537
TI  - The South Australian Cancer Registry: a means of assessing cancer incidence,
      mortality and case survival.
AB  - In 1977, a Cancer Control and Surveillance Unit was established by the South
      Australian government. The infrastructure of the Unit was the State's Cancer
      Registry which was established simultaneously. By 1990, approximately 70,000
      invasive cancer cases had been notified to the Registry for a population which
      had increased from 1,287,550 in 1977 to 1,400,000. In 1990, 2940 cancers were
      notified in males and 2640 in females. The leading sites in males were the
      prostate, lung, colon and melanoma of the skin, while in females they were the
      breast, colon, melanoma of the skin and lung. An increase in age-standardised
      incidence rates for all cancer sites combined has been documented for the 1977
      1990 period. The magnitude of the increase was 7% in males and 12% in females.
      Meanwhile, there were 1544 male cancer deaths and 1203 female cancer deaths in
      1990. Amongst males, age-standardised mortality rates tended to decline in the
      1980's, due largely to a reducing age-standardised incidence of lung cancer. By
      comparison, an increased lung cancer incidence in females contributed to an
      overall increase of 6% in the age-standardised mortality rate for cancers of all
      sites combined in this sex during the life of the Registry. During the period
      1977-1990 there was a 55% increase in the number of new invasive cancers in males
      and females combined. Most of this increase can be attributed to the ageing of
      the South Australian population and to a much lesser degree to population growth.
      During the same period there was a concomitant increase in 43% in the number of
      deaths where the underlying cause of death was cancer. Case survival rates are
      found to be very similar in South Australia to those reported for the United
      States, with about 51% of cases surviving their cancers 5 years after diagnosis.
      5-year survival rates for the diagnostic period, 1983-1990, were generally better
      than for 1977-1982. The evidence for improved survival was strongest for cancers
      of the oesophagus, colon, cervix, prostate and testes, and for low-grade and
      medium-grade lymphomas and chronic myeloid leukaemias. When case survival rates
      were calculated for childhood tumours, significant improvements were found for
      acute lymphatic leukaemias and non-Hodgkin lymphomas for the diagnostic period,
      1983-1990, when compared with 1977-1982.

PMID- 1389538
TI  - Cancer incidence and trends in Bombay, India.

PMID- 1389539
TI  - Hepatitis due to cyproterone acetate.

PMID- 1389540
TI  - DNA ploidy and S-phase fraction in pulmonary carcinoids.

PMID- 1389541
TI  - Substitutive therapy in a case of methotrexate neurotoxicity.

PMID- 1389542
TI  - [Incidence and surgical treatment of extrahepatic abdominal hydatidosis].
AB  - From 1974 to May 1991, 417 patients with abdominal hydatid cyst disease were
      surgically treated. Twenty-eight patients had extrahepatic abdominal cyst disease
      (6.7%). Six patients had only extrahepatic disease where as 22 had associated
      hepatic and extrahepatic cysts. Most frequent sites were the peritoneum (52.7%),
      the spleen (22%) and pelvis (11%). Fourteen out of the 14 CT scans performed,
      detected the extrahepatic cysts. The preferred surgical technique was total
      closed cystectomy (in hepatic and extrahepatic cysts). Resection of the organ
      affected (8 splenectomies, 1 nephrectomy, 1 partial vertebral resection, 1
      orchiectomy and 1 salpingo-oophorectomy) was also performed. There was no
      mortality and morbidity was 32.1%: 3 intraabdominal abscesses, 1 intraabdominal
      haemorrhage, 4 biliary fistulae and 1 partial necrosis of the large bowel. Only 3
      patients (neither were treated with mebendazole) were reoperated on for recurrent
      peritoneal hydatic cyst.

PMID- 1389543
TI  - [Enteral nervous system: importance of 5-hydroxytryptamine in the control of
      digestive motility].

PMID- 1389544
TI  - [Inflammatory fibroid polyp of the ileum].
AB  - A new case of ileal inflammatory fibroid polyp (IFP) is reported. A 76 years old
      woman presented with abdominal pain due to intestinal obstruction; an ileo-ileal
      intussusception caused by an ulcerated submucosal polyp was found at laparotomy.
      The IFP usually appears as a solitary benign lesion, rarely located in the ileum.
      It is made up of fibrous tissue with a dense infiltrate composed predominantly of
      eosinophils.

PMID- 1389545
TI  - [Ulcerative colitis and amyloidosis. Presentation of a case and review of the
      literature].
AB  - A case of ulcerative colitis associated with secondary amyloidosis in a 62-year
      old man who died from septic shock and pneumonia complicating head injury is
      reported. Amyloid deposition was incidentally found at autopsy. Proteinuria and
      hepatomegaly discovered a few days before his death were the only signs of
      amyloidosis. The postmortem examination showed chronic ulcerative colitis
      (remitting form) with pseudo-polyps and amyloid deposition in the liver, spleen,
      pancreas, rectum, adrenals and kidneys. Although secondary amyloidosis
      complicating with Crohn's disease has been frequently reported, amyloidosis
      associated with ulcerative colitis has been exceptionally described and only 10
      cases have been collected from the literature.

PMID- 1389546
TI  - [Bone metaplasia in colorectal carcinoma].
AB  - We report two cases of osseous metaplasia in the polypoid areas of colorectal
      carcinomas. This is an extremely rare condition with no more than 30 cases
      published, that has to be recognized to avoid misinterpretations on biopsies or
      surgical specimens. The pathogenesis is unknown and it does not change the
      biological behaviour of these tumors.

PMID- 1389547
TI  - [Acute viral hepatitis A and C: report of a case].
AB  - We present a case of acute hepatitis by simultaneous A and C virus infection. The
      coinfection was suspected due to the high levels of transaminases lasting more
      than 9 months after onset of the illness. During the early stages of the illness,
      the patient had IgM antibodies to hepatitis A virus. Serological tests for
      hepatitis B and C viruses, cytomegalovirus and Epstein-Bar virus were negative.
      Due to the persistently high transaminase levels, we repeated the serology,
      detecting positive results for hepatitis C antibody, while hepatitis B serology
      remained negative as well that for all other virus tested. With these findings,
      we believe that a patient with hepatitis A of long duration, requires additional
      serological examinations to determine the possibility of coinfection by another
      virus.

PMID- 1389548
TI  - [Dubin-Johnson syndrome. Presentation of 3 cases. Review of the national
      literature].
AB  - Three patients, two male and one female, 42, 64 and 20 years old respectively,
      with a Dubin-Johnson syndrome are reported. Both men referred jaundice since
      several years and in the woman's case, the onset of the illness took place during
      the last term of her second pregnancy. In two patients, liver aspect and it's
      biopsy were diagnostic. In the other, who was hospitalized because of a
      myocardial infarction, a hepatic gammagraphy with Tc 99 HIDA was made. No case
      was associated with biliary lithiasis and only one patient had other members in
      his family with the illness.

PMID- 1389549
TI  - [Duodenal perforation following cimetidine suppression because of leukopenia].

PMID- 1389550
TI  - [Double aorto-enteric fistula].

PMID- 1389551
TI  - [Cholestasis caused by hypersensitivity to flurbiprofen].

PMID- 1389552
TI  - [Digestive hemorrhage caused by gastric varices: usefulness of the techniques of
      endoscopic sclerosis].
AB  - Upper gastrointestinal hemorrhage secondary to gastric varices still has a high
      death rate. Fourteen patients were admitted to our unit with bleeding gastric
      varices from November 1989 to August 1991. Endoscopic injection sclerotherapy
      obtained control of the bleeding in 92.3%; however, recurrences occurred in 33%
      of these cases in the first 24-48 hours, with a death rate of 50% during the
      second stage of the upper gastrointestinal hemorrhage. Total mortality rate was
      21.4%. Of the fourteen patients, nine exhibited junctional varices, while five
      hand fundic varices. In ten of the fourteen patients, gastric varices developed
      during esophageal sclerotherapy. While hospitalized, it was observed that
      patients with gastric varices in the fundus had more recurrences and mortality,
      than those located next to the cardio-esophageal junction. Sclerosis of the
      varices only obtained temporary control of the bleeding with greater frequency of
      recurrences and mortality.

PMID- 1389553
TI  - [Gastric emptying of solids, acid secretion and tobacco in duodenal ulcer].
AB  - We study in a group of patients with endoscopically diagnosed duodenal ulcer (19;
      17 males) and controls (11; 7 males) the gastric emptying of solids through
      scintigraphy and gastric acid secretion by standard tests. In the same way we
      investigated prospectively some clinical data, specially smoking habits. As a
      whole, patients with duodenal ulcer showed an emptying of solids slightly faster
      than controls (T 1/2-minutes-: 85.4 +/- 28.6 in patients with duodenal ulcer
      versus 116.9 +/- 46.5 in controls, p less than 0.03). However, most of our
      patients (15 of 19 or 79%) were found to have a normal emptying rate. No
      correlation was found between secretory outputs and gastric emptying. Smokers
      with duodenal ulcer had a faster emptying that non-smokers with duodenal ulcer (T
      1/2 74.8 +/- 30.05 vs. 99.91 +/- 19.86; p = 0.05).

PMID- 1389554
TI  - [Intestinal inflammatory disease in the province of Soria. Retrospective clinical
      and epidemiologic study from 1981 to 1990].
AB  - The inflammatory bowel disease cases in Soria have been reviewed from 1981 to
      1990. Thirty-two cases of ulcerative colitis (UC) and thirteen cases of Crohn's
      disease (CD) have been found. The mean incidence was 3.2/100.000 inhabitants/year
      in UC and 1.3/100.000/inhabitants/year in CD. The prevalence was 32 and
      13/100.000 inhabitants respectively. We have found a progressive increase in
      incidence in both UC and CD during the period analyzed. Epidemiologic data
      (considering the majority come from rural areas), clinical course, endoscopic and
      radiologic findings, are similar to the results published in the literature. We
      have found a minor percentage that other authors in extraintestinal signs,
      complications and need of surgical intervention.

PMID- 1389555
TI  - [Trophic activity of neurotensin in massive intestinal resection].
AB  - Regulatory peptides are among the main factors affecting the proliferative
      adaptive process of the small bowel; its mechanisms of action remains unknown. An
      80% small bowel resection was done in Wistar rats (250-300 g) randomly assigned
      to two groups: control and neurotensin (300 mu/kg). Jejunal and ileal samples
      were taken on day 14 post-resection and histomorphometric (villous length) and
      proliferative (DNA content) measures were obtained. Results show an increase in
      villous length in the neurotensin group but no changes in DNA content were
      observed. We conclude that neurotensin increases intestinal mucosal growth after
      massive intestinal resection in the rat.

PMID- 1389556
TI  - [Prevalence of hepatitis B markers in non-hospital health personnel].
AB  - Through a hepatitis B prophylaxis campaign, vaccination and serological study was
      offered to 316 nonhospital health personnel of the Health Area of Gandia
      (Valencia). 117 people volunteered (37%); among them, nurses showed the highest
      participation (45.8%) in comparison with doctors, nursing auxiliaries and non
      technical personnel (p less than 0.05). In 22 cases a positive marker could be
      proved; therefore, total prevalence (18.8%) was significantly higher than that of
      the control group, which was 6.8% (p less than 0.01). This prevalence is compared
      with other groups of hospital and nonhospital personnel, and the convenience of
      new studies and the recommendation of active prophylaxis for this subset of
      health workers are discussed.

PMID- 1389557
TI  - [Amyotrophic lateral sclerosis--its problem].

PMID- 1389558
TI  - [Neuropathology of classical and several other types of amyotrophic lateral
      sclerosis].

PMID- 1389560
TI  - [The quantitative investigations on the neuronal loss in ALS].

PMID- 1389559
TI  - [Lewy body-like hyaline inclusion].

PMID- 1389561
TI  - [Clinical and histochemical findings in spinal muscular atrophy].
AB  - The childhood form of the spinal muscular atrophy (SMA) is classically subdivided
      into three groups on the basis of a combination of age of onset, milestones of
      development and age of survival: acute Werdning-Hoffmann (type I), intermediate
      Werdnig-Hoffmann (type II) and Kugelberg-Welander disease (type III). Now we
      examined 7 cases of type I and 9 cases of type II on clinical and histochemical
      ground. Of the total of 16 cases, 5 cases had a family history of the disease.
      (1) In type I, three were males and 4 females. The onset was within 30 days and
      the disease was manifest before or at delivery in 3 cases. The progression was so
      severe. All cases were dead by 10 months. They showed generalized hypotonia,
      abnormal respiration and could not sit without support. In type II, five were
      males and 4 females. The onset of the disease was between the age of 3 and 15
      months. The progression was slow. All patients couldn't walk by themselves at all
      but 7 of them had abilities to sit without support. Clinically it was easy to
      classify type I from type II. (2) The most characteristic histochemical findings
      of both types were group atrophy, fiber hypertrophy, fiber type predominance and
      fibrosis. Though there was a slight difference between two types in histological
      pattern, the basis was so similar. There is controversy about the proper
      classification of recessive childhood SMA. Now it is suggested that the majority
      of both acute and chronic cases are allelic, similar to the patterns of Duchenne
      and Becker forms of muscular dystrophy.

PMID- 1389562
TI  - [Cool storage of fetal rat brain for neural transplantation].
AB  - The availability, storage and transportation of donor tissue are major practical
      problems associated with the potential use of grafted neural cell replacements in
      neurodegenerative diseases. The capacity to collect and maintain viable fetal
      neural tissue would facilitate possible clinical applications, and provide
      opportunities to study various neural diseases. In the present study, we examined
      the effect of cool storage on the survivability of intraventricular rat fetal
      ventral mesencephalic grafts (gestational days 15). In all experiments, fetal
      ventral mesencephalons were dissected out under a dissecting microscope in
      calcium-free magnesium-free buffer (CMF: 0.15 M NaCl, 0.008 M Na2HPO4, 0.0027 M
      KCl, 0.0015 M KHPO4, 0.026 M NaHCO3, with 0.1% glucose, 100 micrograms/ml
      streptomycin, 2.5 micrograms/ml fungizone). Fetal mesencephalic tissue was
      grafted into the lateral ventricle following pregraft refrigeration in calcium
      free magnesium-free buffer at 4 degrees C. Fetal mesencephalic tissue was
      hibernated for 5, 12, 16, 20, 24, 28, 32 hours (group A, B, C, D, E, F and G,
      respectively). As a control group, fetal mesencephalic tissue was grafted into
      the lateral ventricle immediately after dissection. Grafted fetal mesencephalic
      tissue which had been hibernated for 16 hours or less survived well. There were
      no significant decreases in the size of grafts among group A, B, C and the
      control group. In group A, B, C and the control group, clusters of TH-positive
      neurons and dense networks of neuritic profiles within the grafts provided a
      morphological appearance reminiscent of the dendritic bundles that characterize
      the zone reticulate of the substantia nigra in situ.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1389563
TI  - [Seizure susceptibility in aged rats--pentylenetetrazol-induced seizures and
      amygdaloid kindling seizures].
AB  - Seizure susceptibility in male aged rats (21-25 mo. age) was investigated by
      pentylenetetrazol (PTZ)-induced seizures and amygdaloid kindling seizures. Male
      adult rats (3-4 mo. of age) were used as the control group. During 60 min. after
      the administration of PTZ (70 mg/kg, s.c.), the aged rats had a higher incidence
      and a significantly longer duration of generalized convulsion than the control
      group. On the other hand, the kindling rate of the aged rats was significantly
      slower than that of the control. The aged rats remained longer at stage 1-2
      indicative of partial seizures. However, the aged rats skipped stage 3 on their
      way to stage 4-5 (generalized seizures), and showed a more violent stage 5
      seizure than the control group. They had a longer duration of afterdischarges
      (AD) through the kindling process with a significantly faster propagation of AD
      to the contralateral amygdala as compared with the control group. The present
      study suggests that aged rats are prone to convulsion, while they have a
      difficulty in acquisition of epileptogenesis.

PMID- 1389564
TI  - [Significance of the factors in wound healing for the origin of chronic subdural
      hematoma--fibronectin and its related substances].
AB  - The role of substances for wound healing in chronic subdural hematoma was
      investigated. Fibronectin, blood coagulation factor XIII (F X III), alpha 2 
      plasmin inhibitor (alpha 2-PI) and alpha 2-PI plasmin complex (PIC) in hematoma
      fluid were measured, sixty cases of hematoma fluid (15 cases were bilateral
      chronic subdural hematomas) were used for analysis. The levels of fibronectin in
      hematoma fluid ranged widely from 40 to 1068 micrograms/ml. The levels of F XIII
      (except 1 case) in the hematoma fluid were less than 70% (normal plasma level 72
      144%). And also the levels of alpha 2-PI in the hematoma fluid were lower than
      that in normal blood plasma (85-115%). Fibrin, fibronectin, alpha 2-PI and
      collagen crosslinks to these proteins by the catalytic action of the activated F
      XIII. These substrate proteins (except fibronectin) and F XIII were extremely low
      levels for wound healing. Histological analysis of the membrane with dura mater
      obtained from 13 patients was performed by Abidin-Biotin peroxidase Complex
      Method. Fibronectin was identified in outer membrane especially in sinusoidal
      layer. In normal wound healing, fibronectin appears early with the invading
      fibroblast and disappeares within 5 weeks from injury. But in chronic subdural
      hematoma it was not disappeares in 8 weeks after the head injury. The fact
      indicates the neomembrane of the chronic subdural hematoma is not in healing
      stage. This condition in chronic subdural hematoma is unfavorable for wound
      healing. Thus, author suspected that in early phase of wound healing after the
      head injury fibronectin and its related substances may play a role in the
      formation of chronic subdural hematoma.

PMID- 1389565
TI  - [An autopsy case of neuronal type Charcot-Marie-Tooth disease (HMSN type II) with
      nerve deafness and psychiatric symptoms].
AB  - The clinical and pathological findings of a 41-year-old male patient with
      atypical Charcot-Marie-Tooth disease were reported. There were 3 cases of
      subarachnoid haemorrhage, 2 nerve deafness and 2 hereditary motor and sensory
      neuropathy (HMSN) in his family. He had suffered from progressive nerve deafness
      since 5 years old and gait disturbance since 37 years old. He had been admitted
      to the psychiatric hospital 3 times because of hallucinatory-delusional state and
      behavior abnormalities. Neurological examinations at 39 years old revealed that
      he had mental deterioration (IQ 66), nerve deafness, diffuse muscle atrophy, most
      marked distally, sensory disturbance, areflexia, positive Romberg's sign,
      orthostatic hypotension, dysphagia and slurred speech. MCV of median nerve was
      27.8 m/sec, and SCV was not evoked. EEG revealed nonspecific dysfunction of the
      brain. He died of ileus-like condition at 41 years old. General autopsy showed
      haemorrhagic infarction of the jejunum and ileum due to compression of the
      superior mesenteric artery and vein by an adhesion band of connective tissue
      formed after previous appendectomy. Neuropathological examinations revealed
      axonal degeneration and loss of myelinated fibers with schwannosis of anterior
      and posterior spinal nerve roots as well as peripheral nerves. The posterior
      roots were more severely affected than the anterior ones. Ganglion cells of the
      posterior root ganglia showed remarkable degeneration and loss. There was severe
      degeneration of the posterior columns, especially in the gracilis, of the spinal
      cord. Nerve cells in the anterior horns and Clarke's columns also displayed
      conspicuous atrophy or central chromatolysis followed by gliosis. There was
      slight degeneration of the posterior spinocerebellar tracts.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1389566
TI  - [Diffuse reduced uptake in 99m-Tc-HM-PAO SPECT and high level of neuron-specific
      enolase in cerebrospinal fluid in the early stage of Creutzfeldt-Jakob disease].
AB  - We report an autopsy-diagnosed case of Creutzfeldt-Jacob disease (CJD) showing
      diffuse reduced uptake in SPECT and a high level of neuron-specific enolase (NSE)
      in the cerebrospinal fluid (CSF). A 75-year-old woman with a 3-month history of
      progressive gait ataxia and dementia was examined. Four months after onset of the
      disease, she developed an akinetic mutism with normal CT and MRI. She was
      admitted for further examination, and electroencephalography showed periodic
      synchronous discharges. NSE in the CSF showed a high level at 90.6 ng/ml, and
      SPECT showed diffuse reduced uptake in the supratentorial region, with relatively
      spared uptake in the cerebellum. She died 13 months after onset of the disease,
      and the autopsy diagnosis was CJD. SPECT data and the level of NSE in CSF seem to
      be useful for clinical diagnosis and pathogenetic analysis in the early stage of
      CJD.

PMID- 1389568
TI  - Standardization of tibial fractures in the rat.
AB  - The influence of the fracture level on the biomechanical properties of healing
      rat tibial fractures has not been investigated so far, despite the widespread use
      of rats in fracture healing studies. Fractures were produced in four different
      zones in the right rat tibia and immobilized with a K-wire. A fifth group of rats
      was not fractured. After 40 days of healing the fractures and the non-fractured
      bones were tested in three-point bending. A distinct correlation was found
      between fracture level and mechanical parameters: maximum load, maximum
      stiffness, and maximum stress decreased the more distal the fracture was located.
      In the non-fractured bones, maximum load and maximum stress were constant in all
      four zones tested, whereas energy absorption increased in the distal part of the
      tibia. No influence of the healing fracture was found on the contralateral, non
      fractured tibia, compared with the animals left undisturbed, and the mechanical
      properties of the right and the left tibia were found to be symmetrical in terms
      of mean values. Four different methods of determining the area moment of inertia
      were investigated, and the simple method of approximating the cross section to an
      elliptical annulus was found to correlate well with the area moment of inertia,
      determined from computer tracings of bone slices prepared from the test specimens
      after the bending test. The computer tracings were corrected for the compression
      of the specimens caused by the mechanical test.

PMID- 1389567
TI  - Inhaled beclomethasone decreases serum osteocalcin in postmenopausal asthmatic
      women.
AB  - There are very few data as yet to quantify the effect of inhaled corticosteroids
      on bone metabolism, although the use of these drugs as a first-line treatment in
      bronchial asthma has widened. We determined the effect of three dose levels (200,
      1000, 2000 micrograms/day, three weeks each) of inhaled beclomethasone on
      specific characteristics of bone metabolism in nine postmenopausal women with new
      asthma without any previous corticosteroid therapy. Significant decrease was
      noted in the mean serum morning osteocalcin concentration between the baseline
      and after nine weeks of beclomethasone (from 4.4 to 3.1 micrograms/l, p = 0.005).
      Significant increase in serum total and ionised calcium was found, although the
      parameters measuring bone resorption itself did not change. The results show that
      especially high-dose inhaled beclomethasone decreases serum osteocalcin in post
      menopausal asthmatic women. Further studies are needed to assess the effects of
      inhaled beclomethasone, both on the ability of the osteoblasts to form bone
      matrix and on the density of bone during a longer treatment period on inhaled
      corticosteroids.

PMID- 1389569
TI  - Age-dependent morphometric alterations in the distal femora of male and female
      rats.
AB  - Morphologic parameters, bone area, bone-to-bone + marrow ratio, periosteal-to
      periosteal + endocortical surface ratio, mean trabecular thickness, and surface
      to-volume ratio were studied in the epiphysis and metaphysis of the distal femora
      of male and female rats (Heiligenberg strain) between birth and the end of the
      lifespan. With increasing age, bone area, bone-to-bone + marrow ratio, and mean
      trabecular thickness increases, whereas periosteal-to-periosteal + endocortical
      surface ratio and surface-to-volume ratio decreases in both parts of bone during
      the first 150 days. Afterwards, periosteal-to-periosteal + endocortical surface
      ratio, mean trabecular thickness, and surface-to-volume ratio remain constant,
      whereas the bone area and the bone-to-bone + marrow ratio decrease. Modeling data
      were measured by use of the vital labeling technique with calcein. From the
      stained bone area, the bone formation, the bone resorption, and the periosteal
      mineral apposition rates have been calculated. The bone formation rate, about
      13,000%/year in the metaphysis and 2,000%/year in the epiphysis, respectively, is
      greatest after birth and decreases continuously with increasing age to 3.5%/year
      for both bone regions. During the first 150 days the bone resorption rate is
      lower than the bone formation rate, leading to an increase in bone area, but
      afterwards it is higher so that the area decreases. Likewise the periosteal
      mineral apposition rate is greater in the metaphysis (24 microns/day at day 50)
      than in the epiphysis (14 microns/day at day 50), but after 700 days it is
      comparable for both bone regions (0.07 microns/day). The absolute values of body
      weight, femur length, and bone area of epiphysis and metaphysis are greater in
      male rats; only the mean trabecular thickness and the periosteal mineral
      apposition rate are comparable in both sexes. The relative values of bone-to-bone
      + marrow ratio, periosteal-to-periosteal + endocortical surface ratio, bone
      formation rate, and bone resorption rate are comparable for both sexes.

PMID- 1389570
TI  - Lack of changes in histomorphometric, bone mass, and biochemical parameters in
      ovariohysterectomized dogs.
AB  - A predictable animal model with skeletal remodeling characteristics similar to
      those of humans is needed to facilitate the understanding of the mechanism of
      postmenopausal osteoporosis. We have utilized the ovariohysterectomized (Ovh) dog
      to examine cellular and biochemical responses to estrogen depletion and PTH
      stimulation. Histomorphometric measurements of bone biopsies taken prior to
      (first biopsy) and five months after the operation (second biopsy) showed no
      significant differences in static and dynamic parameters. Bone mineral density of
      the excised vertebrae displayed the same values between the two groups six months
      after surgery. Between the second biopsy and sacrifice, two infusion studies were
      performed. A two-hour infusion of EDTA followed by a two-hour recovery period
      elicited a rapid response in PTH production, highly correlated to the changes in
      ionized calcium, but no significant difference in response was observed between
      Sham and Ovh groups. A short-term (24-h) infusion of 1-34 hPTH increased
      circulating ionized calcium and 1,25-(OH)2-D levels to a similar extent in both
      groups. The levels of alkaline phosphatase were constant and both groups showed a
      small but nonsignificant increase in osteocalcin. The lack of sizable responses
      in histomorphometric, bone mass, and biochemical parameters may limit the utility
      of dogs for the study of cancellous bone loss in ovarian-dysfunction
      osteoporosis.

PMID- 1389571
TI  - Dual-energy X-ray absorptiometry of lumbar vertebrae: relative contribution of
      body and posterior elements and accuracy in relation with neutron activation
      analysis.
AB  - The bone mineral content of 34 lumbar vertebrae obtained from ten cadavers (three
      men, seven women; age 61-88 years) was measured using a pulsed source dual-energy
      X-ray absorptiometry (DEXA) apparatus. Scanning was performed in the frontal
      projection and was repeated on the vertebral bodies obtained after removal of the
      posterior elements of the vertebrae. Subsequently a nondestructive neutron
      activation analysis (NAA) was performed. The mineral content of the vertebral
      bodies was found to represent (mean, SEM) 53.0% (1.9%) of the content of the
      whole vertebrae. The mineral content of the vertebral bodies assessed with NAA
      (BMC NAA) and with DEXA (BMC DEXA) showed a high correlation: BMC NAAA = (1.016 x
      BMC DEXA) + 0.990 r = 0.949 (p less than 0.001). We conclude that the mineral
      content of lumbar vertebral bodies can be accurately measured in vitro in a water
      environment by DEXA, and that the mean contribution of the posterior elements of
      the vertebra to the calcium hydroxyapatite content of whole vertebrae measured in
      the frontal projection is as high as 47.0%.

PMID- 1389572
TI  - Inhibition of bone resorption by the bisphosphonate BM 21.0955 is not associated
      with an alteration of the renal handling of calcium in rats infused with
      parathyroid hormone-related protein.
AB  - Hypercalcaemia of malignancy is determined by an increase of bone resorption
      and/or renal tubular reabsorption of calcium (Ca). However, this latter component
      has been found to vary in certain patients during therapy with bone resorption
      inhibitors such as bisphosphonates. We investigated the possible effects of the
      highly potent bisphosphonate BM 21.0955 on the renal handling of Ca in
      thyroparathyroidectomized rats made hypercalcaemic by the stimulation of both
      bone resorption and renal tubular reabsorption of Ca induced by the chronic
      infusion of parathyroid hormone-related protein (PTHrP). Dose-dependent
      inhibition of bone resorption by BM 21.0955, as indicated by the decrease in
      fasting urinary Ca excretion from 64.0 +/- 7.3 to 6.7 +/- 3.1 nmol/ml GFR, was
      associated with a change in plasma Ca from 2.97 +/- 0.10 to 2.63 +/- 0.16 mmol/l.
      However, the relationship between urinary Ca excretion and plasma Ca was not
      altered, either at endogenous plasma Ca concentration or during the acute
      infusion of Ca. Similarly, an index of renal tubular reabsorption of Ca
      calculated from the slope of the linear portion of the relationship between
      urinary Ca and plasma Ca, which was increased by PTHrP administration, was not
      influenced by BM 21.0955 therapy (2.59 +/- 0.15 vs. 2.55 +/- 0.11 mmol/l GFR).
      These results indicate that BM 21.0955, which is one of the most potent
      bisphosphonates inhibiting bone resorption, did not affect the renal tubular
      reabsorption of Ca enhanced by PTHrP.

PMID- 1389573
TI  - Trabecular bone pattern factor--a new parameter for simple quantification of bone
      microarchitecture.
AB  - The stability of trabecular bone depends not only on the amount of bone tissue,
      but also on the three-dimensional orientation and connectedness of trabeculae,
      which is summarized as trabecular microarchitecture. In previous studies we could
      demonstrate that in three-dimensional bone tissue the relation of trabecular
      plates to rods is reflected in the ratio of concave to convex surfaces of the
      bone pattern in two-dimensional bone sections. For the quantification of the
      connectedness of these bone patterns we developed a new histomorphometric
      parameter called Trabecular Bone Pattern factor (TBPf). The basic idea is that
      the connectedness of structures can be described by the relation of convex to
      concave surfaces. A lot of concave surfaces represent a well connected spongy
      lattice, whereas a lot of convex surfaces indicate a badly connected trabecular
      lattice in two-dimensional sections. By means of an automatic image analysis
      system we measure trabecular bone area (A1) and perimeter (P1). A second
      measurement of these two parameters (now A2 and P2) is done after a simulated
      dilatation of trabeculae on the screen. This dilatation results in a
      characteristic change of bone area and perimeter depending on the relation of
      convex to concave surfaces. TBPf is defined as a quotient of the difference of
      the first and the second measurement: TBPf = (P1 - P2)/(A1 - A2). First
      measurements of TBPf in 192 iliac crest bone biopsies of autopsy cases show that
      there is not only age-related loss of bone volume, but also a decrease of
      trabecular connectedness. By means of TBPf we can demonstrate a significant
      difference in the age-related loss of trabecular connectivity between male and
      female individuals.

PMID- 1389574
TI  - Comparative study of iliac crest and subchondral femoral bone in osteoarthritic
      patients.
AB  - This is a study of trabecular bone changes in selected regions of the femoral
      head. Iliac crest bone from osteoarthritic (OA) and control groups is compared to
      the bone from regions in the femoral head. The regions are the subchondral
      principal compressive and tensile areas. These areas of highest and lowest stress
      undergo dramatic change with OA. The compressive region has total cartilage loss
      and eburnation. Bone histomorphometry was done on undecalcified tissue sections
      stained by the von Kossa silver method and counter-stained with haematoxylin and
      eosin. Iliac crest histomorphometry is similar for the OA and control groups. The
      femoral trabecular structure in the stress regions changes in opposing directions
      with OA. In the compressive region the structural variables (BV/TV and BS/TV)
      increase [corrected], and in the tensile region decrease. Femoral bone turnover
      indices (OV/TV, OS/BS, and ES/BS) are no different, but femoral bone structure is
      different from that of the iliac crest. In OA patients there is no significant
      increase in iliac crest trabecular bone volume. The iliac crest is not useful to
      assess the bony changes in femoral OA.

PMID- 1389575
TI  - Development and evaluation of an index to predict early postmenopausal bone loss.
AB  - An index to predict individual postmenopausal bone loss is presented. The index
      is developed by means of data from a 10-year prospective Norwegian study in which
      bone mass of the distal forearm was measured annually in 73 women. All the women
      were 47 years old and premenopausal at inclusion. Independent risk factors for
      postmenopausal bone loss were identified by applying multivariate regression
      analysis on anthropometric, biochemical, nutritional, and life-style variables
      measured at menopause. The analysis identified low body weight, reduced renal
      phosphate reabsorption, and smoking as significant independent risk factors, and
      by means of these three factors a predictive index for postmenopausal bone loss
      was developed. This index was validated by using data from a 10-year longitudinal
      Dutch study, in which bone mass of the proximal radius was measured annually in
      86 women, aged between 49 and 57 years and perimenopausal at inclusion. We
      defined women with the highest index score as "high-risk persons." According to
      this definition approximately 25% of the perimenopausal women were classified as
      high-risk persons, and the estimated sensitivity/specificity/positive predictive
      power were 36%, 89%, and 74%, respectively, when used to select women with a
      postmenopausal bone loss above average. We conclude that the index may be helpful
      in identifying healthy perimenopausal women in whom bone mass measurements should
      be considered.

PMID- 1389576
TI  - The effects of dietary protein insufficiency and excess on skeletal health.

PMID- 1389577
TI  - Michigan: dental similarities and differences between the USA and Britain.

PMID- 1389578
TI  - 'Orthodontic relapse'.

PMID- 1389579
TI  - 'Orthodontic relapse'.

PMID- 1389580
TI  - 'Permanent damage to inferior alveolar and lingual nerves during the removal of
      impacted third molars'.

PMID- 1389582
TI  - Pulse oximetry--a method of vitality testing for teeth?

PMID- 1389581
TI  - 'Post mortem identification of a body by use of dental evidence'.

PMID- 1389583
TI  - A brief account of eruption.

PMID- 1389584
TI  - The essential features of microorganisms and the rationale for antimicrobial
      therapy.
AB  - Antimicrobial agents have had a major impact on the control of most bacterial
      diseases; however, viral, fungal, protozoal and helminthic diseases have
      generally been less amenable to drug therapy. The reason for this lies in the
      different structural and physiological features that each group of microorganisms
      have. This article will outline the basic features of the various types of
      microorganisms, and relate these to the mode of action of commonly used
      antimicrobial agents.

PMID- 1389585
TI  - Bond strengths of dentine bonding agents to dentine.
AB  - This study assessed comparatively the tensile bond strengths to dentine of four
      resin dentine bonding agents. Flat surfaces were produced in the occlusal dentine
      of human third molars, finished with 600-grit paper and prepared for bonding to
      Silux Plus composite with Gluma, Prisma Universal Bond 2, Scotchbond 2 and
      Tenure. After 24 hours in water and 250 thermal cycles, the specimens were loaded
      in tension to failure on an Instron machine. There were 20 specimens in each test
      group. An analysis of variance and Duncan's test showed that the bond strengths
      of Scotchbond 2 (22.8 +/- 7.2 MPa) and Prisma Universal Bond 2 (20.1 +/- 7.8 MPa)
      were similar but significantly higher than those of Tenure (14.3 +/- 5.3 MPa) or
      Gluma (12.3 +/- 6.4 MPa). A Weibull analysis confirmed the superiority of
      Scotchbond 2 and Prisma Universal Bond 2. Scotchbond 2 and Prisma Universal Bond
      2 specimens failed either in an adhesive-cohesive mode, or cohesively through the
      composite or the dentine. It was concluded that Scotchbond 2 and Prisma Universal
      Bond 2 are effective and are the dentine bonding agents of choice.

PMID- 1389586
TI  - Differences in time devoted to practice by male and female dentists.
AB  - Previous studies have found that female dentists work fewer hours per year than
      male dentists. This study examined factors which may explain the differences in
      hours worked per year that exist between male and female dentists in private
      practice. In 1988, a weighted, stratified random sample of dentists in Australia
      was surveyed by mailed questionnaire. There were 855 respondents (response rate =
      75.5%) with 566 dentists from private practice (361 males and 205 females).
      Annual time devoted to dental practice was significantly lower for females, for
      dentists who were not the sole earner of the family income, and for dentists with
      young children. A significant interaction between sex of dentist and child age
      showed that hours per year in practice decreased only for females with young
      children. Hours worked per year were significantly higher among female dentists
      with no children, or older children. For males, hours worked remained at a higher
      level. The amount of time devoted to dentistry requires monitoring in the
      estimation and projection of capacity to supply dental services.

PMID- 1389587
TI  - A visit to the University of Lagos Dental School.

PMID- 1389588
TI  - The risk management of infections.
AB  - Unfortunately, risk management, that is avoiding lawsuits, is a retro-active
      pastime instead of being pro-active. What this means is that we often take action
      only after a problem has manifested itself, rather than identifying potential
      problems and correcting them. This is, however, only human nature and occurs in
      most other walks of life. In dental malpractice, what appears to have been
      happening during the past few years in California is that plaintiff's lawyers
      have identified a problem and then started to sue dentists for it (and even run
      courses on how to sue dentists for it!), after which the profession has tried to
      take steps to identify the cause of the problem, and has then attempted to reduce
      it or eliminate it altogether. In the past, the dental malpractice companies (the
      equivalent of the Medical Protection Society and Medical Defense Union) were
      merely bystanders who paid out on claims and subsequently raised premiums
      accordingly. Now that most of the malpractice companies in California are
      actually run by (and often owned by) members of the profession, they are much
      more interested in getting involved at a very early stage, as soon as a potential
      problem is identified, in order to take action so that premiums do not rise
      unnecessarily.

PMID- 1389589
TI  - 'The dentists revolt'.

PMID- 1389590
TI  - Selection criteria for dental radiography.

PMID- 1389591
TI  - Network marketing.

PMID- 1389593
TI  - Fee crisis.

PMID- 1389592
TI  - Fee crisis.

PMID- 1389594
TI  - Fee crisis.

PMID- 1389595
TI  - Specialisation.

PMID- 1389596
TI  - 'Permanent damage to inferior alveolar and lingual nerves'.

PMID- 1389597
TI  - 'Allergic reactions to rubber gloves in dental patients'.

PMID- 1389598
TI  - The structure and function of the temporomandibular joint.
AB  - Although characterised by having a synovial membrane lining the nonarticulating
      surfaces within the joint capsule, in some ways the temporomandibular joint (TMJ)
      is an atypical joint. This paper highlights the differences between the TMJ and
      other movable joints with a description of the structure, innervation blood
      supply and musculature. Also included are details of how the TMJ moves--the
      effectors of movement and the various reflexes controlling movement of the joint.

PMID- 1389599
TI  - General dental practitioners' needs for continuing education on the management of
      fissure caries.
AB  - A process of identifying GDPs' perceptions of their needs for continuing
      education on one topic area is described. The method employed a combination of
      two traditional approaches for assessing educational needs, the so-called
      'wisemen' approach and interviews with members of the target audience. The
      process identified three groups of GDPs with differing educational needs. Their
      perceptions of their educational needs are described, and the advantages and
      disadvantages of the process discussed and compared with other methods of
      assessing educational needs. The study confirmed the importance of identifying
      educational needs in the development of an educational programme.

PMID- 1389600
TI  - Fluoridation in Anglesey: a clinical study of dental caries in mothers at term.
AB  - A study of dental caries was carried out involving 1537 mothers who attended St
      David's Hospital, Gwynedd, between July 1986 and July 1987 for their confinement.
      The study was 'blind' in respect of residence. The mean DMFT value for mothers
      with continuous residence in the non-fluoridated Gwynedd mainland was 13.6 and
      the mean DMFT value for mothers living in the Anglesey Health Unit who had
      consumed fluoridated mains water from birth was 30% lower at 9.5 (P less than
      0.0001). The confidence interval for the difference between means was 3.4-4.9.
      The samples from the two areas showed no significant differences in social class
      and age group structures. The percentage of Anglesey mothers with DMFT exceeding
      15 was less than one-sixth of that for mainland mothers and the percentage of
      those with DMFT less than 6 was three times greater. The mean DMFS value for
      occlusal sites in premolars was 3.9 for mainland Gwynedd and for Anglesey 52%
      less at 1.9 (P less than 0.0001) with a confidence interval of 1.6-2.4. For
      smooth surface sites in posterior teeth, the difference was not as pronounced,
      with a mean DMFS value for mainland of 20.3 and for Anglesey 42% less at 11.8 (P
      less than 0.0001) with a confidence interval of 7.5-9.6. The results showed that
      child-bearing women continued to enjoy important benefits from water fluoridation
      into their early thirties.

PMID- 1389601
TI  - Adenomatoid hyperplasia in the palate: another sheep in wolf's clothing.
AB  - Adenomatoid hyperplasia is a rare idiopathic non-inflammatory, non-neoplastic and
      benign lesion of minor salivary glands, that typically presents with a tumour
      like mass in the palate. A 77-year-old patient is described.

PMID- 1389602
TI  - What kind of people want to become dentists? General Dental Council Recruitment
      Working Party survey of first year undergraduate dental students.
AB  - Above all, the survey has provided a clear, if complex, description of the
      population of first year dental students: who they are and where they have come
      from; why they are doing the course and what they want to achieve from it. A
      number of specific conclusions about recruitment gaps can be drawn from the
      information received from the survey, namely: i) Girls at mixed-sex schools are
      apparently less likely to enter dentistry than their counterparts at all-girls'
      schools. This, however, is part of a much wider issue which encompasses the
      question of science versus arts choices amongst male and female pupils. ii) Some
      dental schools have a very high concentration of students whose home is the local
      region. Wider national publicity for these schools could be attempted. iii) In
      East Anglia, the East Midlands, Yorkshire and Humberside and the West Midlands,
      the number of qualified school leavers who become dental students is below
      average. iv) Family dentists and orthodontists are in a very strong position to
      encourage interested patients to enter the profession beginning at an early age,
      and with guidance could encourage these children towards additional sources of
      information and advice, such as the General Dental Council, which at the moment
      appear to be under-used. v) The information on dentistry provided by most careers
      advisers could be improved. In particular, careers teachers and form
      teachers/tutors are a widely contacted source of guidance but the information
      they were able to provide was not rated highly. University open days and
      residential courses are successful and might be used further.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1389603
TI  - What more do we have to do?

PMID- 1389604
TI  - Your mouth and HIV.

PMID- 1389605
TI  - Undergraduate teaching in geriatric dentistry.
AB  - In the last quarter of a century the elderly population has increased rapidly and
      now represents 18% of the UK population. The profile of the elderly population is
      changing. There is a projected increase in the number of people aged 75 and over
      of 46.4% between the years of 1985 and 2025. The expected rise in people aged 85
      and over is even more dramatic at 99.2%.

PMID- 1389606
TI  - A pit of our own making.

PMID- 1389607
TI  - Fee crisis.

PMID- 1389609
TI  - 'Aspiring dental students'.

PMID- 1389608
TI  - Alternative dentistry.

PMID- 1389610
TI  - 'References'.

PMID- 1389611
TI  - HIV health workers.

PMID- 1389612
TI  - 'A case for a dental surgeon at regional radiotherapy centres'.

PMID- 1389613
TI  - 'Alternatives to toothpaste'.

PMID- 1389614
TI  - 'Contributing factors to stress'.

PMID- 1389615
TI  - The cost of infection control.

PMID- 1389616
TI  - Serious professional misconduct arising out of dental anaesthesia and sedation.
AB  - This paper reviews three recent decisions of the Judicial Committee of the Privy
      Council on appeal from decisions of the Professional Conduct Committee of the
      General Dental Council, in which questions of general anaesthesia, sedation and
      resuscitation were raised. The recommendations of the Poswillo Report on general
      anaesthesia, sedation and resuscitation in dentistry of March 1990 are considered
      with respect to these three cases, and an assessment made as to whether or not
      the incidents which gave rise to them would have occurred had the recommendations
      been implemented. The implications of the Poswillo Report for the maintenance of
      professional standards of conduct by the General Dental Council in relation to
      the use of general anaesthesia, sedation and resuscitation are discussed.

PMID- 1389617
TI  - A survey of disease changes observed on dental panoramic tomographs taken of
      patients attending a periodontology clinic.
AB  - Dental panoramic tomographs (DPTs) were taken consecutively of 500 patients
      referred to a specialist periodontal department by general dental practitioners
      in order to assist in the diagnosis of the severity of the periodontal disease.
      Analysis of these DPTs showed 316 (63.2%) of these patients to have some form of
      dental abnormality unrelated to periodontal disease. The DPT was shown to be a
      valuable screening technique for clinical practice.

PMID- 1389618
TI  - Dental care of patients susceptible to infective endocarditis.
AB  - McGowan and Tuohy carried out a survey in Belfast in 1968 to identify patients
      with cardiac lesions susceptible to infective endocarditis. They also asked
      whether adequate precautions had been taken by the patients' medical and dental
      advisers in respect of antibiotic cover for dental surgical procedures. This
      survey has now been repeated in the Belfast and Glasgow Dental Schools. When
      compared with those of 1968, the results of these recent studies show that while
      more 'at risk' patients are receiving antibiotic cover for dental surgical
      procedures there is still room for improvement in the advice given to patients by
      medical and dental practitioners.

PMID- 1389619
TI  - Cardiopulmonary resuscitation skills of dental personnel.
AB  - This study assessed the cardiopulmonary resuscitation (CPR) skills of 25 dental
      personnel. Theory was tested by multiple choice questionnaire (MCQ) and practical
      skills assessed using a recording Resusci-Anne manikin. The assessment was based
      upon the recommendations of the Resuscitation Council of the UK. Seven of the 16
      dental students and six of the nine house officers tested passed the MCQ
      examination. All failed the practical assessment. It is concluded that more
      emphasis should be placed upon CPR instruction in undergraduate dental courses
      and that regular update courses are advisable to maintain CPR skill.

PMID- 1389620
TI  - Public perceptions of the funding of NHS dental services.
AB  - A survey was carried out of 102 members of the general public, asking for their
      views of the recent changes in the government funding of NHS dentistry.
      Approximately 80% of those surveyed had heard about the changes. The majority
      thought that the implications of the change would be a rise in costs to patients
      and a fall in the number of NHS dentists.

PMID- 1389622
TI  - The hygienist's dilemma.

PMID- 1389621
TI  - Tooth mutilation in Angola.
AB  - In common with many countries throughout sub-Saharan Africa, some of the many
      tribes which comprise the indigenous population of Angola practise various forms
      of tooth mutilation. Three examples associated with distinctive tribes are
      described and compared with similar practices in neighbouring countries and their
      references from the literature.

PMID- 1389623
TI  - Dental personnel planning and the single market: problems ahead?
AB  - Recently Whitehouse expressed concern about the possible implications of the
      legislation regarding the freedom of movement of labour within the European
      Community upon dental policy. Particular reference was made to the possibility of
      a major inflow of dental personnel to the United Kingdom. This paper looks at the
      evidence on which such worries appear to be based and examines the possibilities
      that this could have for planning dental personnel requirements in the UK. Dental
      personnel are defined in this paper as dental practitioners.

PMID- 1389624
TI  - 'Community dentistry in the dental faculties'.

PMID- 1389625
TI  - 'The dentists revolt'.

PMID- 1389627
TI  - 'References'.

PMID- 1389626
TI  - Allergic reactions to rubber.

PMID- 1389628
TI  - 'References'.

PMID- 1389629
TI  - The value of hygienists.

PMID- 1389630
TI  - 'The comparative strengths of commercial glass ionomer cements'.

PMID- 1389631
TI  - Odontogenic bacteraemia and intraligamental analgesia.

PMID- 1389632
TI  - The anterior open bite.

PMID- 1389633
TI  - Mastication and swallowing: an overview.
AB  - The cycles of jaw and tongue movement during feeding produce not only the
      breakage of food but its intra-oral transport; which activity predominates
      depends upon the physical characteristics of the food. When hard food is eaten
      and tooth-food-tooth contact is made during jaw closure, the velocity of closing
      is suddenly reduced, producing two clearly different phases of closure; during
      the second phase the activity of the jaw closing muscles is much increased.
      Conversely, in cycles with a mainly transport function (eating soft food), the
      antero-posterior movements of the tongue are much greater; this alters the time
      and rate at which the jaw opens. The pattern of jaw movement during closing and
      during opening consequently varies with food consistency. The evidence suggests
      that sensory input controls the form of the cyclical tongue and jaw movements.
      However the basic plan of movement is produced by the activity of a brainstem
      pattern generator which receives input from both cerebro-cortical and peripheral
      sources. The swallow that occurs in normal feeding consists of the equivalent of
      the classical second stage of swallowing inserted into the occlusal or initial
      jaw opening phase of an otherwise standard cycle. Although leakage of traces of
      food or saliva into the vallecula appears to be a peripheral sensory input of
      major importance in inducing such a swallow, the execution of the swallow is due
      to a pattern generator in the brainstem.

PMID- 1389634
TI  - General anaesthesia in the dental surgery: a comparison of propofol and
      methohexitone.
AB  - General anaesthesia was assessed in 100 dental patients in general dental
      practice using either propofol or methohexitone. Mean induction doses were 1.7
      mg/kg and 1.5 mg/kg for propofol and methohexitone, respectively. Anaesthesia was
      maintained with nitrous oxide and oxygen, supplemented in the majority of cases
      with halothane. Both groups were comparable in relation to satisfactory surgical
      conditions and recovery. The maximum heart rate following induction of
      anaesthesia was significantly greater in the group given methohexitone. Despite
      the satisfactory results obtained in this study the need for full resuscitation
      facilities will encourage the trend towards most dental general anaesthesia
      taking place in a hospital environment.

PMID- 1389635
TI  - Effects of the removal of composite resin restorations on Class II cavities.
AB  - Composite resin has such good aesthetic qualities that it is often difficult to
      identify the tooth-restoration interface, yet this is particularly important
      should the material require complete removal. Following the in-vitro removal of
      direct and indirect composite resin restorations from Class II cavities
      significant changes in cavity size and shape were recorded. Thirty-eight cavities
      were studied from both occlusal and proximal aspects and the final cavity size
      was compared to the original cavity. There was a significant increase in cavity
      size with a mean increase of 37% for the direct composite cavities and 35% for
      the indirect cavities, although the range of values is large. Following
      restoration removal, occlusal surfaces were seen to increase in 71% of teeth and
      proximal surfaces in 75% of teeth. There was no significant difference between
      the results for direct and indirect composite restorations. Occlusal dovetails
      and cavity undercuts were created in cavities which did not contain these
      features initially.

PMID- 1389636
TI  - Dentistry in Poland.
AB  - A visit to the Orthodontic Institute in Warsaw was kindly sponsored by American
      Orthodontics in order to enable a straight wire typodont course to be conducted.
      The entire orthodontic department turned out for the course, and it proved to be
      a stimulating and enjoyable few days. This report details the state of
      orthodontics in Poland and aims to outline various similarities and differences
      between dental training in Warsaw and in Great Britain, both at undergraduate and
      postgraduate levels.

PMID- 1389637
TI  - Concept analysis of anxiety.
AB  - Anxiety, a nursing diagnosis that impacts clients in all settings and nurses
      throughout the profession, is clarified through the technique of concept
      analysis. Uses of the concept of anxiety in prominent theories of human behavior
      and in nursing are reviewed. Four critical attributes occurring in all cases of
      anxiety are identified--model cases, a related case, a contrary case, and an
      illegitimate case are presented. Antecedents to anxiety are identified.
      Consequences of anxiety are discussed. Empirical referents that demonstrate
      occurrence of the concept of anxiety are determined, classified, and related to
      critical attributes. This concept analysis provides an essential conceptual base
      for instrument development and clinical research on anxiety.

PMID- 1389638
TI  - Axes: focus of taxonomy II.
AB  - A number of persistent issues in the nursing diagnosis community have challenged
      the ability of one nursing diagnosis taxonomy to account for nursing's practice.
      The North American Nursing Diagnosis Association (NANDA) Taxonomy Committee,
      charged with the preparation of one taxonomy for all, has struggled with some of
      these issues and has initiated development of axes. The issues, figuratively
      speaking, become the axes. The axes are intended to describe the dimensions of
      the human condition. This article, third in a series of four, describes the
      process and development of the proposed axes.

PMID- 1389639
TI  - Toward further understanding of nursing diagnosis: an interpretation.

PMID- 1389640
TI  - Don't just stand there. Say something!

PMID- 1389641
TI  - Decreased cardiac output in the critical care setting.
AB  - The specific aim of this exploratory, descriptive study was to demonstrate that
      the nursing diagnosis, decreased cardiac output, contains at least seven separate
      and specific components. Forty critical care nurses completed a questionnaire
      about seven different case studies, or vignettes. Each vignette reflected one of
      the following: myocardial injury, arrhythmias, decreased preload, myocardial
      ischemia, increased afterload, drug effects, and cardiac surgery alterations.
      Mean scores were used to validate the specific subcategories. Analyses of
      variance were used to demonstrate statistically significant differences among
      them. Six of the labels were supported, providing preliminary evidence for the
      validity of these components of decreased cardiac output.

PMID- 1389643
TI  - Measurements of T1 and T2 over time in formalin-fixed human whole-brain
      specimens.
AB  - T1 and T2 were measured in 5 formalin-fixed human whole-brain specimens as a
      function of time. Gray matter/white matter contrast reversal was observed around
      the 4th day and was considered to be due to the greater decrease in T1 in gray
      than in white matter. A possible explanation for this is that the decomposition
      of the myelin phospholipid structure by formalin somewhat counteracts the general
      reductive effect of the fixation procedure on relaxation times.

PMID- 1389642
TI  - MR imaging of pituitary macroadenomas before and after transsphenoidal surgery.
AB  - MR findings before and after transsphenoidal surgery were evaluated in 6 cases.
      T1-weighted (TR/TE 600/20) sagittal and coronal images with 2 or 4 acquisitions
      were obtained, using 3-mm slice thickness and 0.3-mm interslice gaps. Of 18 MR
      examinations, 13 included coronal i.v. contrast medium enhanced images. Image
      quality, sinus cavernosus invasion, identification of normal pituitary tissue and
      tumor size were examined. All MR studies clearly demonstrated the macroadenomas
      whether 2 or 4 acquisitions were used, and whether i.v. contrast medium was
      administered or not. Surgically confirmed sinus cavernosus infiltration was seen
      in 4 patients. The pituitary stalk was identified separate from the tumor in 2
      patients, and the gland in one. There was reduction in tumor size over time,
      indicating that final radiologic assessment after transphenoidal surgery is best
      performed 4 to 6 months postoperatively. It should not be necessary to routinely
      include i.v. contrast medium injection in the postoperative evaluation of
      macroadenomas.

PMID- 1389645
TI  - Temporomandibular joint movement. Evaluation of protrusive splint therapy with
      GRASS MR imaging.
AB  - Ten temporomandibular joints (TMJs) of 5 healthy volunteers and 19 TMJs of
      internal derangements in 16 patients with splint therapy were examined with MR
      imaging. T1-weighted images were obtained only in the closed mouth position, and
      gradient recalled acquisition in steady state (GRASS) images were obtained in
      active opening and closing phases, allowing a pseudodynamic display of TMJ
      movement. All patients received protrusive splint treatment. The usefulness of MR
      imaging to assess the efficacy of splint therapy was evaluated. Corrected disk
      position with the splint in place was clearly demonstrated in 9 TMJs,
      corresponding with elimination of reciprocal clicking. Ten other TMJs of anterior
      disk displacement without reduction showed uncorrected disk position by the
      splint. This information could confirm the therapeutic efficacy, or suggest other
      treatment alternatives. GRASS MR imaging can provide accurate and physiologic
      information about disk function in initial and follow-up assessment of protrusive
      splint therapy.

PMID- 1389646
TI  - CT appearances of normal and obstructed submandibular duct.
AB  - CT scans of 40 patients without pathology in the floor of the mouth or the
      submandibular glands were reviewed. Intraglandular ducts were visualized in 27
      and extraglandular ducts in 3 patients. The CT appearances of dilated
      submandibular ducts are described in 4 patients with proven causes of
      obstruction. Widening of the narrow gutter between the mylohyoid and hyoglossus
      muscles in one scan level is a prominent feature. An intra- or extraglandular
      duct diameter of 3 mm or more indicates possible obstruction, and the CT images
      should be scrutinized to reveal the cause.

PMID- 1389644
TI  - Gadodiamide injection and gadopentetate dimeglumine. A double-blind study in MR
      imaging of the CNS.
AB  - A double-blind, randomized parallel phase III study in MR imaging of the central
      nervous system was conducted to compare the safety and diagnostic utility of
      gadodiamide injection and gadopentetate dimeglumine at a dose of 0.1 mmol/kg b.w.
      in 60 adult patients. Seven patients in the gadodiamide injection group
      experienced 10 adverse events, 5 of the events possibly related to the contrast
      agent. In the gadopentetate dimeglumine group 5 patients reported 3 contrast
      agent-related adverse events out of 8 events. All events were transient and
      required no treatment. Seven incidents of patient discomfort, and some minor
      changes in vital signs and laboratory parameters were of no clinical concern.
      Contrast enhancement was observed in 60% and 44% of the patients with structural
      abnormalities in the gadodiamide injection group and gadopentetate dimeglumine
      group, respectively. No difference in overall efficacy was observed. Gadodiamide
      injection was found to be a safe and effective contrast agent.

PMID- 1389647
TI  - Diagnosis of aneurysm of superior thyroid artery by CT and MR imaging.
AB  - A 51-year-old man presented with a nonpulsatile anterior neck mass which
      suggested a thyroglossal duct cyst. At CT a small cystic mass was revealed. The
      mass contained a well-defined, crescent-shaped, low-density area with homogeneous
      contrast enhancement. On MR T2-weighted spin-echo and gradient-echo images the
      mass was as hyperintense as the neck vessels. Angiography and operation confirmed
      an aneurysm of the left superior thyroid artery with a mural thrombus.

PMID- 1389648
TI  - Ultrasound guided tumour biopsy in the anterior mediastinum. An alternative to
      thoracotomy and mediastinoscopy.
AB  - To evaluate percutaneous ultrasound (US) guided tumour biopsy of the anterior
      mediastinum all patients scheduled for open mediastinal biopsy were considered
      for percutaneous biopsy during a 2-year period. US guided biopsy was chosen when
      CT had shown the tumour to be in contact with the thoracic wall. US guided biopsy
      was performed in 23 patients on 28 occasions. The procedure was technically
      successful in all cases and no complications occurred. In 27 of 28 cases the
      biopsy diagnosis was identical to the final diagnosis. In one patient with a
      malignant lymphoma a false diagnosis of connective tissue remnant was reached. US
      guided tumour biopsy of the anterior mediastinum is a safe, cost-effective and
      reliable method and a good alternative to the traditional biopsy techniques via
      mediastinoscopy or thoracotomy.

PMID- 1389649
TI  - Bedside chest radiography using digital luminescence. A comparison between
      digital radiographs reviewed on a personal computer and as hard-copies.
AB  - The introduction of picture and archiving communicating systems is currently
      being evaluated in several institutions. We decided, as an intermediate step, to
      see if image quality after transferral to a personal computer (PC) is sufficient
      for the diagnostic needs in an intensive care unit. Seventy-five portable digital
      chest radiographs were studied both as hard-copies and on a monitor after
      transferral to a PC. Two chest radiologists and one anesthesiologist reviewed the
      examinations. Our intention was to evaluate if everything that is routinely
      checked by the anesthesiologist is demonstrable after electronic transfer to a
      local workstation. We found practically no difference between the performance of
      monitor and film for the whole material.

PMID- 1389650
TI  - MR imaging of acute renal cortical necrosis. A case report.
AB  - MR imaging of a patient with acute renal cortical necrosis secondary to massive
      bleeding following an abortion is presented. The kidneys were enlarged with a
      high signal intensity observed in the renal cortex on both T1- and T2-weighted
      images. Follow-up MR imaging showed thinned renal cortex of low signal intensity
      on both pulse sequences representing renal cortical calcification which was
      confirmed on conventional radiography and CT.

PMID- 1389651
TI  - Polyetiology of renal allograft dysfunction. Does calculation of the resistive
      index still make sense?
AB  - In 101 consecutive patients with renal allograft dysfunction a correlation of
      Duplex Doppler sonography (DDS) with histopathologic reports of simultaneously
      performed biopsies was made. Renal vascular impedance was estimated by
      calculating the resistive index (RI). A total of 290 different specific
      histologic diagnoses (mean 2.1 +/- 0.84 diagnoses/biopsy) was noted. With
      increasing time interval to transplantation, single diagnoses as cause of
      allograft dysfunction decreased. DDS could not reliably differentiate, exclude,
      or grade any of the common causes of renal allograft dysfunction like vascular
      and/or cellular rejection, chronic rejection, acute tubular necrosis, cyclosporin
      nephrotoxicity, relapse of glomerulonephritis and infection. Follow-up studies
      after established histologic diagnosis in 19 patients with persisting allograft
      dysfunction demonstrated a lack of sensitivity of DDS to significant superimposed
      causes of transplant malfunction. We conclude that biopsy is still necessary to
      direct proper therapy of renal allograft dysfunction.

PMID- 1389652
TI  - Leiomyosarcoma in Poland's syndrome. A case report.
AB  - We describe a 56-year-old female with absence of the right pectoralis muscles,
      aplasia of the right breast, and skeletal deformities of the right hand, typical
      of Poland's syndrome. Following complaints of lower abdominal pain, a CT
      examination revealed an 8-cm mass in the right anterior pelvic wall. Surgical
      resection of the mass revealed a high-grade, poorly differentiated
      leiomyosarcoma. Poland's syndrome is known to be associated with a high incidence
      of leukemia but this is the first description of its association with
      leiomyosarcoma. Although we cannot exclude the possibility of a chance
      association, it is reasonable to assume that, similar to other syndromes with
      multiple congenital anomalies, the association with an increased incidence of
      malignancy is an integral part of the underlying genetic abnormality.

PMID- 1389653
TI  - Nonresectable adenocarcinoma of the rectum assessed by MR imaging before and
      after chemotherapy and irradiation.
AB  - Thirty-four patients with nonresectable adenocarcinoma of the rectum, defined as
      tumor fixation at digital examination, were examined with MR. All 34 patients
      had, according to MR imaging, perirectal tumor growth. In 23 (68%) of the
      patients, the tumor has reached an adjacent organ. Eight of these patients had
      disturbances of the MR characteristics in the adjacent organ which proved to be
      due to overgrowth, i.e., to tumor invasion into these structures. In the
      remaining 15 patients, without disturbed MR characteristics, 7 had tumor
      overgrowth at laparotomy. When there was a visible space between the tumor and
      adjacent organs, there was no sign of tumor overgrowth at laparotomy, except in
      one case. In 24 patients, examined both before and after combined irradiation and
      drug therapy, tumor regression was registered after treatment. MR imaging seems
      to be useful in the assessment of resectability and to evaluate preoperative
      anticancer treatment in patients with nonresectable rectal carcinoma.

PMID- 1389654
TI  - Anal sphincter size measured by endosonography in healthy volunteers. Effect of
      age, sex, and parity.
AB  - The anal sphincter muscles consist of the circular internal and external
      sphincters together with the sling-shaped associated puborectalis muscle. Ten
      men, 10 women with no vaginal deliveries, and 10 women with one or more vaginal
      deliveries were studied with anal endosonography using a 7 MHz multiplanar
      endoprobe. The thickness of the internal sphincter and the thickness, length, and
      cross-sectional area of the external sphincter were measured and related to age,
      sex, and parity. Reproducibility was assessed by similar measurements on
      different days in 10 volunteers. Anal sphincter size was the same in men and
      women and was not affected by the number of child births. Internal sphincter
      muscle thickness increased with age. Anal manometry and electromyography with an
      anal sponge were performed in all volunteers but the results did not correlate to
      any of the anal sphincter dimensions. Our conclusion is that although there are
      some limitations, endosonography can be used to determine the size of the anal
      sphincter muscles.

PMID- 1389655
TI  - Thrombosed hemorrhoid mimicking rectal carcinoma at CT.
AB  - A 46-year-old man with cirrhosis and portal hypertension complained of lower
      pelvic pain. CT of the rectum raised a strong suspicion of a rectal tumor.
      However, rectal examination, anoscopy, direct rectoscopy, and, unfortunately,
      post-mortem dissection, failed to confirm its existence. Nevertheless, large flat
      hemorrhoids were evident. Review of the patient's chart disclosed the presence of
      large thrombosed hemorrhoids detected by rectal examination prior to the CT
      examination. It is suggested that rectal hemorrhoids be included in the
      differential diagnosis of rectal tumor shown by CT in patients with portal
      hypertension.

PMID- 1389656
TI  - Hydatid disease of the spleen. Ultrasonography, CT and MR imaging.
AB  - Seven patients with hydatid disease of the spleen were examined by radiography,
      ultrasound, CT, and in one case MR imaging. The observations were confirmed by
      patho-anatomic findings except in 2 patients where high indirect hemagglutination
      tests confirmed the diagnosis. In one patient primary, and in the others
      secondary, echinococcosis of the spleen was assumed to be present. Secondary
      hydatid disease of the spleen was caused by rupture of liver cysts with abdominal
      and pelvic dissemination. Ultrasound and CT findings of the cysts and cystic
      calcifications are described. In one patient MR imaging indicated prolapse of a
      splenic hydatid cyst into the left hemithorax, confirmed by patho-anatomic
      examination.

PMID- 1389657
TI  - Aberrant left gastric vein directly draining into left portal venous system. A
      case report.
AB  - A 66-year-old man with early gastric cancer and liver cirrhosis was diagnosed by
      preoperative angiography as having an aberrant left gastric vein communicating
      directly with the left lateral portal vein system. This communication was
      confirmed during operation for the gastric cancer. Our report is the first of an
      aberrant left gastric vein showing direct communication with the left portal vein
      system.

PMID- 1389658
TI  - Bone marrow extension and pelvic bone marrow activity in alcoholic liver disease.
      A RES scintigraphic investigation.
AB  - Red bone marrow extension and increased central bone marrow activity were found
      in 21 patients with alcoholic liver disease investigated with scintigraphy of the
      reticuloendothelial system. The patients had no concurrent disease known to alter
      red bone marrow distribution. The bone marrow extension and the increased pelvic
      bone marrow activity may be explained as being secondary to a decreased
      radiocolloid uptake in the liver and could thus be a sign of decreased
      reticuloendothelial capacity.

PMID- 1389659
TI  - Comparison of dual energy X-ray absorptiometry of the proximal femur with
      morphologic data.
AB  - Measurements of bone mineral density (BMD) of the proximal femur (including
      femoral neck, Ward's triangle and trochanteric region) were compared with the
      Singh index grading in 40 normal subjects (20 male, 20 female) and in 116
      patients (18 male, 98 female) referred for assessment of possible osteoporosis.
      Additionally, the BMD and the Singh index of 12 cadaver specimens (6 male, 6
      female) of the proximal femur were compared with each other and with the
      histomorphology of the femoral necks of the specimens. Although there was a good
      correlation of Singh index with BMD in the group of male patients with suspected
      osteoporosis and in the series of bone specimens, there was a poor correlation in
      the group of female patients as well as in the normal controls and in the patient
      population as a whole. There was also poor correlation of Singh index values with
      histomorphologic data, whereas the BMD measurements correlated well with the
      amount of calcified bone found histologically in the femoral necks of the bone
      specimens. We conclude that the Singh index cannot be used to predict BMD of the
      proximal femur accurately.

PMID- 1389660
TI  - Pharmacokinetics of iopentol in patients with chronic renal failure.
AB  - Iopentol 350 mg I/ml was injected in doses of 265 to 533 mg I/kg b.w. (mean 417
      mg I/kg b.w.) in 10 patients with advanced nondiabetic chronic renal failure (S
      creatinine 672 +/- 259 mumol/l (mean +/- SD)). Urine (10 patients) and feces (7
      patients) were collected at 24 h intervals for 5 days after the injection. The
      elimination of iopentol was delayed. Five days after injection a mean of 54%
      (range 35-79%) of the dose was recovered in urine, and 11% (0-20%) in feces. Mean
      elimination half-life was 28.4 h, about 14 times the half-life found in healthy
      volunteers. The apparent volume of distribution was 0.27 l/kg b.w., indicating
      distribution only to extracellular fluid. Using renal iopentol clearance as
      reference value, GFR was overestimated by 40 to 60% with iopentol total
      clearance, showing extrarenal elimination of iopentol. The difference was most
      pronounced in patients with low GFR. In conclusion, this study shows an
      extrarenal elimination of iopentol and demonstrates a substantial increase in the
      fecal elimination in patients with severe renal failure.

PMID- 1389661
TI  - Addition of sodium to the nonionic contrast medium iohexol during coronary
      angiography in man. Lack of electrocardiographic or hemodynamic effects.
AB  - It has recently been claimed that lack of sodium in nonionic contrast media may
      increase the risk of ventricular arrhythmias during coronary angiography. Thus,
      the influence of sodium addition to the nonionic contrast medium iohexol was
      studied in 75 patients with severe coronary heart disease. The study design was
      randomized, parallel and double-blind, and iohexol was given either with or
      without addition of NaCl (28 mmol/l). Both formulations induced a transient drop
      in arterial blood pressure, and prolongation of the QT interval and QRS duration
      at 10 s only (p less than 0.01). The electrical QRS axis was significantly
      changed by the coronary artery injections after 10 s, but not later. No
      differences between iohexol with and without NaCl were observed for any of the
      variables studied. No serious arrhythmias were observed. Thus, the addition of
      NaCl (28 mmol/l) to iohexol did not influence the electrocardiographic or
      hemodynamic changes induced by iohexol during coronary angiography.

PMID- 1389662
TI  - Granulocyte adherence after intravenous and intraarterial injection of ioxaglate
      or iohexol.
AB  - The effect of iohexol and ioxaglate on granulocyte adherence to nylon fibers was
      investigated with blood from 15 patients undergoing angiography, and from 24
      patients undergoing excretory urography. Decreased adherence and increased
      numbers of granulocytes in the circulation were observed soon after injection of
      iohexol or ioxaglate in the aorta, or injection of ioxaglate i.v. Increased
      adherence and decreased numbers of granulocytes in the circulation were observed
      soon after injection of iohexol i.v. The differences were small soon after the
      injection of contrast media (CM). More pronounced decreased adherence and
      increased numbers of granulocytes were detected 2 and 5 hours after injection in
      the aorta for both CM.

PMID- 1389664
TI  - CT of the wrist in suspected scaphoid fracture.
AB  - Bone scan and sagittal projection CT of the scaphoid was performed in 10 patients
      with clinically suspected scaphoid fractures. The primary and follow-up plain
      radiographs were negative or equivocal for fracture. CT examination demonstrated
      scaphoid fracture in 7 patients and normal findings in 3. It is concluded that CT
      of the scaphoid can replace bone scan to diagnose or rule out fracture in
      institutions where nuclear medicine facilities are not available.

PMID- 1389665
TI  - CT attenuation of normal liver parenchyma on delayed scanning with iohexol.
AB  - Twenty patients were examined with CT of the liver before, during, and 4 to 6
      hours after i.v. administration of 60 g iodine (200 ml iohexol). The attenuation
      of normal liver parenchyma was measured. The mean attenuation of normal liver
      parenchyma on nonenhanced scanning was 62.6 HU and on delayed scanning 78.7 HU.
      It seems that iohexol is a suitable contrast medium for delayed scanning of the
      liver.

PMID- 1389663
TI  - Radiographic contrast media and release of neutrophil specific proteins in vitro
      and after intravenous injection.
AB  - The neutrophil granulocytes contain granules in which different proteins are
      present. When activated the neutrophils degranulate and thereby release some of
      these proteins to the surroundings. Some of these proteins are specific for this
      type of cell, e.g., lactoferrin and elastase. To investigate the influence of
      contrast media (CM) on this release, blood was incubated with diatrizoate,
      ioxaglate, iohexol, iodixanol, hyperosmolar saline, and hyperosmolar mannitol at
      different concentrations, and the amount of the neutrophil specific proteins
      lactoferrin and elastase were measured. Decreasing protein concentrations were
      observed for increased medium concentrations, suggesting that the degranulation
      process of the neutrophils was inhibited by the CM. The protein concentrations
      were lowest after incubation with the two ionic media diatrizoate and ioxaglate.
      Significantly decreased values of plasma lactoferrin were observed one min after
      i.v. injection of iohexol or ioxaglate in 82 patients undergoing urography. There
      was no significant difference between the two CM.

PMID- 1389666
TI  - Organizational empowerment: moving shared governance beyond nursing.

PMID- 1389668
TI  - One federal court rejects NLRB's restrictive definition of a health care
      supervisor.

PMID- 1389667
TI  - Managing diversity: a call to action for nursing.

PMID- 1389669
TI  - HCFA cuts federal funds to hospital in AIDS discrimination case.

PMID- 1389670
TI  - Preceptor to predecessor: enhancing the quality of future nurse executives.

PMID- 1389671
TI  - Computer technology is taking over.

PMID- 1389672
TI  - Total quality management and the marker umbrella model for quality management.
      Part II. An overview.

PMID- 1389673
TI  - Ten guiding principles for innovation.

PMID- 1389675
TI  - A guide to productive collaboration between the CNO and the CEO.

PMID- 1389674
TI  - Clinical engineering: integrating all caregivers in the design of high quality
      patient care delivery systems.

PMID- 1389676
TI  - Female chauvinism, male nurses and sexism: issues for the nurse executive.

PMID- 1389677
TI  - At issue: dysfunctional people in management roles.

PMID- 1389678
TI  - The changing relationships between hospitals and physicians.

PMID- 1389679
TI  - New strategies in nurse recruitment.

PMID- 1389681
TI  - Six steps toward empowering your nurse managers.

PMID- 1389680
TI  - The budget-cut nightmare--how to keep it from happening to you.

PMID- 1389682
TI  - Three nurse executives tell how they foster the communication that makes their
      quality programs work.

PMID- 1389683
TI  - Suppression by retinoic acid of epidermal growth factor receptor
      autophosphorylation and glycosylation in cultured human head and neck squamous
      carcinoma cells.
AB  - The epidermal growth factor receptor (EGF-R) gene is overexpressed or amplified
      in various human squamous cell carcinomas, including those of the head and neck
      (HNSCC). Earlier we found that beta-all-trans-retinoic acid (RA) inhibited the
      growth and suppressed the aberrant squamous cell differentiation of several
      cultured HNSCC cell lines. Here we examined the effects of RA on the expression
      and function of EGF-R in two HNSCC cell lines, 1483 and 183, which exhibit
      distinct states of squamous cell differentiation, EGF-R mRNA levels, and
      responses to the growth inhibitory effects of RA. Treatment with RA (1 microM, 7
      days) of the RA-sensitive 1483 cells decreased the level of EGF-R mRNA two- to
      four-fold and the binding of 125I-EGF to the cell surface by 30%-35%. In
      contrast, RA treatment of the 183 cells did not alter the EGF-R mRNA level or the
      binding of 125I-EGF. Other effects of RA on EGF-R structure and function were
      similar in both cell lines. RA did not alter the amount of immunoprecipitable
      [35S]methionine-labeled cellular EGF-R, 125I-cell surface labeled EGF-R, EGF-R
      internalization, or transforming growth factor alpha (TGF-alpha) mRNA. More
      important, RA treatment of both cell lines decreased EGF-R autophosphorylation
      activity detected in immune-complex-kinase assay by about three- and five-fold in
      the 1483 and 183 cells, respectively. Likewise, RA decreased the glycosylation of
      EGF-R in both cell lines. In the 1483 cells, RA suppressed the incorporation of
      either glucosamine or fucose by about 50%, whereas in the 183 cells RA suppressed
      the incorporation of fucose by about 80%. These results demonstrate that RA can
      modify the structure of the EGF-R by decreasing its glycosylation and suggest
      that these changes may suppress the autophosphorylation activity of the receptor
      kinase. The RA-induced changes in EGF-R do not correlate with the effect of RA on
      the growth of the cells but may be related to the suppression of squamous cell
      differentiation in the 1483 cells.

PMID- 1389684
TI  - 13-cis-retinoic acid and cancer chemoprevention.
AB  - Chemoprevention is the newest strategy for controlling and managing cancer. At
      present, the multistep character of epithelial carcinogenesis makes this disease
      process the most amendable to chemopreventive interventions, which occur in the
      postinitiation, preinvasive phases. Chemoprevention study has focused on oral
      carcinogenesis because of its excellent preclinical models, well-defined
      premalignant phase (leukoplakia), ease of monitoring, and link through field
      carcinogenesis to other epithelial carcinogeneses of the upper and lower
      aerodigestive tract. Retinoids, the derivatives of vitamin A, are the most
      studied chemopreventive agents, and 13-cis-retinoic acid is the best-studied
      chemopreventive retinoid. Laboratory study of the newly discovered nuclear
      receptors of retinoic acid is closing in on the precise mechanism of retinoid
      action. Only 13-cis-retinoic acid, at high doses, has established chemopreventive
      activity, which is in suppressing oral premalignancy and preventing second
      primary head-and-neck tumors. Preclinical and clinical work in the other
      aerodigestive sites of the lung and esophagus are at an early phase of study with
      no conclusive results currently available. High-dose 13-cis-retinoic acid also
      has achieved significant activity in preventing invasive carcinomas of the skin.
      High-dose 13-cis-retinoic acid, however, is not ideal for widespread
      chemoprevention approaches because of its toxicity. The toxicity-to-risk balance
      is delicate and complicated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389685
TI  - Epidermal growth factor receptor as a target for therapy with antireceptor
      monoclonal antibodies.
AB  - The epidermal growth factor (EGF) receptor is a potential target for antitumor
      therapy. Recent studies from many laboratories have found that this receptor is
      expressed in high levels on a variety of human tumor cells. Furthermore, the EGF
      receptor has been implicated in autocrine stimulation of cell growth in a number
      of experimental studies. We have produced anti-EGF receptor monoclonal antibodies
      (MAbs), which block the binding of EGF and transforming growth factor alpha (TGF
      alpha), and can prevent ligand-stimulated activation of EGF receptor tyrosine
      kinase. These MAbs have been useful in studies of EGF receptor function.
      Experiments utilizing the MAbs to block ligand binding have demonstrated that
      autocrine stimulation of EGF receptor phosphorylation can occur via an
      extracellular pathway, involving TGF-alpha-mediated activation of EGF receptor on
      the surface of the cell. The capacity of anti-EGF receptor MAbs to inhibit cell
      proliferation has provided evidence of an autocrine stimulatory pathway in
      cultures of malignant human skin, breast, colon, and lung cells. Growth of a
      variety of human tumor xenografts can be inhibited in situations where autocrine
      dependency is demonstrable in cell culture. Imaging studies with anti-EGF
      receptor MAb labeled with indium 111 (111In) demonstrated selective uptake in
      xenografts expressing high receptor levels. Based on these observations, a phase
      I trial was carried out with 111In-labeled anti-EGF receptor MAb 225 IgG1 in
      patients with advanced squamous cell lung carcinoma, a tumor that invariably
      expresses large numbers of EGF receptors. In the case of squamous lung carcinoma,
      there is evidence that overexpression of EGF receptors correlates with worse
      clinical stage and worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389686
TI  - Systematic development of bombesin/gastrin-releasing peptide antagonists.
AB  - Several families of very potent bombesin (Bn) receptor antagonist analogues have
      recently been developed and their biological potencies evaluated in a number of
      in vitro systems including guinea pig and rat pancreatic acini and Swiss 3T3
      cells. These studies showed that analogues can exhibit diverse properties ranging
      from full antagonists, partial agonists, or full agonists depending on the assay
      system and animal species employed. We have developed two classes of more potent,
      shorter chain antagonists based on [psi CH2NH(13-14)]Bn(6-14) and desMet14Bn(6
      13)NH2 structures. [D-Phe6 psi Leu13-Leu14] Bn(6-14)NH2 was a potent antagonist
      (Ki 6nM) in Swiss 3T3 cells and guinea pig acini but exhibited 10% partial
      agonist activity and lower binding affinity (Ki 60 nM) in rat acini. The partial
      agonism could be eliminated by using p-Cl-Phe or D-Phe at the C-terminus and
      partially eliminated using D-4-Cl-Phe in position 6. With the antagonist [D
      Phe6]Bn(6-13)NH2 (Ki 96 nM), alkyl substituents on the amide group increased
      affinity 25-fold with the propylamide being the most potent peptide (Ki 4 nM) in
      3T3 cells or guinea pig acini. It did, however, have high 40% partial agonist
      activity in rat acini. Alkyl esters or hydrazide derivatives were, in contrast,
      pure antagonists in all systems tested with [D-Phe6]Bn(6-13)OMe having the
      highest affinity in all systems and also excellent in vivo properties. All of the
      potent antagonists examined had little affinity for neuromedin B--preferring
      bombesin receptors, which had entirely new ligand structure-activity
      relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389687
TI  - Effects of neuropeptides on human lung and breast cancer cells.
AB  - We evaluated the effect of seven classes of neuropeptides [bradykinin,
      cholecystokinin 26-33 (CCK), neurotensin, arginine-8 vasopressin (AVP), tyr-4
      bombesin (BN), somatostatin, and motilin] on 18 human lung cancer and four human
      breast cancer cell lines to determine the pattern of responses. Flow cytometric
      analysis of Indo-1 AM-loaded cells was used to quantitate the intracellular
      calcium response of individual cells produced by these peptides alone or in
      simultaneous or sequential combinations. All 18 lung cancer cell lines responded
      to one or more peptide classes with classic small cell lines displaying the
      greatest responsiveness, followed by variant small-cell lines and non-small-cell
      lung cancer cell lines. Breast cancer cell lines demonstrated little or no
      response to any peptide. There was great variability in the magnitude of response
      and pattern of response in individual cell lines and between cell lines.
      Bradykinin was the most potent peptide and produced responses in the largest
      number of lung cancer cell lines. Simultaneous administration of active peptides
      produced greater intracellular calcium release than single peptides, though in a
      less than additive manner. Response to each peptide was followed by a refractory
      period lasting several hours or more. The refractoriness was peptide-specific,
      implying that each peptide has a distinct pathway, at least at the receptor
      level. Bradykinin antagonists could abrogate the calcium response to bradykinin
      but not to other peptides. Similarly, specific peptide antagonists for CCK, BN,
      and AVP blocked the response for only their specific agonist.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1389688
TI  - Differential stimulation of the growth of lung-metastasizing tumor cells by lung
      (paracrine) growth factors: identification of transferrin-like mitogens in lung
      tissue-conditioned medium.
AB  - Certain metastatic tumor cells successfully form metastases at particular organ
      sites, and their organ colonization properties cannot be explained by mechanical
      or anatomic factors. These tumor cells possess the ability to colonize such sites
      through preferential adhesion to organ microvessel endothelial cells,
      preferential organ invasion by expression of particular degradative enzymes and
      response to organ motility factors, and preferential organ growth by response to
      growth factors present at relatively higher concentrations in the target organ.
      The likelihood that target organ-associated growth factors exist and are
      important in metastatic colonization has been approached by studying the
      mitogenic effects of target organ extracts, fragments, or conditioned media on
      poorly and highly metastatic tumor cells that show organ preference of
      metastasis. We previously described the isolation of a major organ-derived
      (paracrine) growth factor from lung tissue-conditioned medium. Characterization
      of this mitogen has demonstrated that it is a transferrin or a transferrin-like
      glycoprotein, and antibodies to transferrin can remove significant growth
      activity from lung tissue-conditioned medium. Further demonstration of the
      existence and characterization of metastasis-associated organ (paracrine) growth
      factors and their receptors will be helpful in understanding the organ preference
      of metastasis.

PMID- 1389689
TI  - Expression of prohormone processing enzymes in neuroendocrine and non
      neuroendocrine cells.
AB  - The biosynthesis of many peptides thought to have autocrine or paracrine effects
      on cell growth requires a series of enzymatic steps. The level of expression of
      two of these posttranslational processing enzymes was compared in several
      endocrine and non-neuroendocrine cell lines. Peptidylglycine alpha-amidating
      monooxygenase (PAM; EC 1.14.17.3) is a bifunctional copper- and ascorbate
      dependent enzyme essential in the formation of alpha-amidated peptides.
      Carboxypeptidase H (CPH; EC 3.4.17.10) removes basic residues from the
      carboxyterminus of the products of endoproteolytic cleavage of prohormones and is
      generally essential in the formation of substrates for PAM. PAM messenger RNA
      (mRNA) and activity were detectable in both endocrine (AtT-20, GH3) and non
      neuroendocrine (L, 3T3, COS, BRL, C127) cells. Except for BRL cells, CPH mRNA and
      enzymatic activity were detectable in all the cell lines. BRL cells contained no
      detectable CPH mRNA and had a different carboxypeptidase B-like activity. Thus,
      expression of secretory granule-associated processing enzymes is not limited to
      cells of a classic neuroendocrine phenotype.

PMID- 1389690
TI  - Control of tumor cell biology through regulation of peptide hormone processing.
AB  - Control of the biology of individual cells, organs, and organisms is achieved
      through an interplay of a host of specific interactions, many involving peptide
      hormones as modulators or effectors. In tumor cells these processes may result in
      uncontrolled growth as a consequence of autocrine and/or paracrine growth
      effects. Most peptide hormones are bioactive only after processing of the
      precursor prohormone by posttranslational processing enzymes. The enzymes
      involved with the production of bioactive peptides, in particular those
      associated with peptide alpha-amidation, provide potential targets for disruption
      of posttranslational processing mechanisms as a means of regulation of the
      progression of tumor cells. This information provides a rational basis for
      consideration of inhibition of autocrine neuropeptide synthesis as a strategy for
      chemointervention.

PMID- 1389691
TI  - Biomarker intermediate endpoints and cancer prevention.
AB  - Detection of cancer is the definitive endpoint in the conduct of chemoprevention
      trials. There are, however, several reasons why cancer as the endpoint may not be
      feasible or ethical: 1) the usage of patients with easily followable
      preneoplasias may preclude the development of cancer, and 2) the time to a cancer
      event may be long or the incidence uncommon, even in individuals at high risk.
      Two major types of biomarker intermediate endpoints should be considered: 1)
      those that identify individuals at high risk and 2) those that serve as a
      surrogate for cancer. Various epidemiologic features, including family history,
      have been used to estimate relative risk. This approach, however, only slightly
      decreases the size of populations needed for chemoprevention trials and only
      little addresses the question of individual risk. Advances in understanding the
      genetic basis for cancer will lead to the development of probes that will help
      assess risk for many cancers. Innumerable biomarker intermediate endpoints can be
      identified as associated with cancer formation, including genetic, epigenetic,
      and histologic features. The challenge is not in identifying potential biomarker
      intermediate endpoints but in showing that they are relevant. Carcinogenesis has
      been shown to be carcinogen, inhibitor, dose, tissue, and species specific; it is
      likely that relevant biomarker intermediate endpoints will need to be identified,
      studied, and verified in human models. The upper aerodigestive system should be a
      rich source for biomarker intermediate endpoint studies, as tissue is readily
      available, the carcinogenic process can be monitored, and there are currently
      available reasonable compounds to use in biomarker intermediate endpoint
      modulation and chemoprevention trials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389693
TI  - Role of biology and prevention in aerodigestive tract cancers.
AB  - Primary prevention aimed at smoking control and chemoprevention for high-risk
      persons or patients at risk for a second cancer provide strong potential for
      cancer prevention and control of aerodigestive cancers. The National Cancer
      Institute (NCI) has a major effort to build this area of research. The Third
      Upper Aerodigestive Tract Cancer Task Force Workshop, held in 1989 under the
      auspices of the National Cancer Institute's Organ System Program, reviewed the
      opportunities for chemoprevention research on aerodigestive epithelial cancers
      such as the regulation of growth and differentiation in normal and malignant
      cells. The chemoprevention program's drug development effort is evaluating
      several promising candidate agents for future clinical testing and the NCI
      clinical intervention program is supporting several trials of selected
      chemoprevention agents with demonstrated potential for inhibiting cancers of the
      lung, bronchus, oral cavity, and esophagus. Of special interest to this program
      is the assessment of beta-carotene, retinol and related synthetic retinoids, and
      several vitamin and mineral combinations under study in high-risk international
      populations. Chemoprevention in the medical setting is a major focus of NCI's
      Community Oncology Program (CCOP), a network designed not only to increase
      accrual of patients to trials but also to speed adoption of state-of-the-art
      therapies. Public health strategies are directed toward control of exposure to
      tobacco. The focal point for these activities is NCI's Smoking, Tobacco, and
      Cancer Program (STCP). STCP smoking cessation efforts are targeted at specific
      populations that are at greater risk for developing cancer including youth,
      minority and ethnic groups, women, smokeless tobacco users, and heavy smokers.
      Two of the world's largest controlled intervention trials conducted by the STCP
      are underway: the Community Intervention Trial for Smoking Cessation (COMMITT),
      which focuses on 6.5 million heavy smokers in 11 pairs of matched communities in
      North America, and the American Stop Smoking Intervention Study (ASSIST), a
      coalition model designed to reach millions of Americans through existing health
      promoting systems.

PMID- 1389692
TI  - Rational targets for the early detection of lung cancer.
AB  - The fact that routinely effective treatments for disseminated lung cancer are not
      available has prompted the search for effective early detection systems. It is
      important to identify lung cancer while it is still confined to the bronchial
      epithelium and is potentially curable with local modalities. We have previously
      reported on an immunologically based assay to identify antigens expressed on shed
      bronchial epithelial cells. This assay resulted in a statistically significant
      correlation of immunostaining with the eventual development of lung cancer 2-4
      years prior to routine clinical detection. Attempts to further improve this
      approach require an understanding of the basis for its success. Based on the work
      of Hakomori and coworkers, this difucosylated Lewis X structure would be a likely
      marker of carcinogenic transformation of the bronchial epithelium. In fact, an
      antibody to this structure was useful for sputum immunocytochemistry analysis for
      early lung cancer detection. Other carbohydrate structures would also be
      reasonable markers to evaluate for early detection application, based on the
      known pattern of expression of these structures in fetal, dysplastic, and
      neoplastic lung tissue. Another antibody used for sputum immunostaining
      recognizes a 31-kd protein structure; the antibody is not a known member of a
      likely class of early detection targets. The reported cases of lung cancer missed
      by the immunostaining approach included principally adenocarcinoma of the lung,
      suggesting that the addition of a marker(s) of that type of morphologic
      differentiation should be considered. Markers to dissect the various forms of
      lung adenocarcinoma are being characterized and are available for evaluation in
      early detection applications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389694
TI  - Early events in the neoplastic transformation of respiratory epithelium.
AB  - The complex process of epithelial carcinogenesis is composed of discrete biologic
      events including the early activation events of "initiation" and "promotion." For
      lung cancer, these events are only now being elucidated. Despite the
      identification of possible target genes and their mutations, the "initiation"
      events for lung cancer remain poorly understood. The identification of these
      "initiation" events is a crucial step toward the development of practical
      molecular markers for early detection of this disease. The reversible process of
      tumor promotion remains somewhat enigmatic but is a promising target for
      chemoprevention. A wide range of substances, including asbestos and various
      substances in cigarette smoke, behave as tumor promoters for lung cancer. They
      appear to promote tumor formation by inducing cellular proliferation mediated in
      part by growth factors. The intracellular signals these factors provide are
      ultimately translated into cellular growth via steps involving nuclear
      transcription factors. Early response genes such as the jun and fos gene family
      members encode such nuclear transcription factors which are expressed in lung
      cancer cells and primary bronchial epithelial cells. The expression of these
      transcription factors is highly responsive to stimulation by growth factors
      including serum, transforming growth factor, and gastrin-releasing peptide. A
      more thorough understanding of this process will allow the development of
      molecular and/or pharmacologic antagonists that can interfere with the biologic
      process of tumor promotion and therefore function as chemoprevention agents.

PMID- 1389695
TI  - Animal models for chemoprevention of respiratory cancer.
AB  - Of the several models for lung carcinogenesis, two appear appropriate for
      chemoprevention studies based upon dose response, tumor type, and tumor
      localization. One model utilizes the direct-acting carcinogen methylnitrosourea
      (MNU), and the other utilizes a carcinogen (diethylnitrosamine) requiring
      metabolic activation. Tumors appear rapidly in both models (within 6 months), and
      the model systems are responsive to modulation by several classes of potential
      chemopreventive agents. For example, the retinoid N-(4-hydroxyphenyl) retinamide
      reduces the incidence of lung adenosquamous carcinoma, but retinol or beta
      carotene are ineffective when administered alone. However, concomitant
      administration of these compounds reduces the incidence of non-neoplastic
      dysplasias as well as adenosquamous carcinomas of the lung. In the MNU system,
      retinoids in general have been ineffective in reducing the incidence of
      tracheobronchial squamous-cell carcinomas.

PMID- 1389696
TI  - Chemopreventive studies in Barrett's esophagus: a model premalignant lesion for
      esophageal adenocarcinoma.
AB  - Barrett's esophagus is a premalignant lesion in which the lower esophagus is
      lined with metaplastic columnar epithelium rather than the normal stratified
      squamous epithelium. It is a precursor lesion for adenocarcinoma of the
      esophagus. We are studying Barrett's esophagus as a model premalignant lesion for
      adenocarcinoma from the standpoint of identifying biologic markers of increased
      cancer risk as well as therapeutic strategies for eradicating the lesion.
      Ornithine decarboxylase (ODC) activity in Barrett's mucosa was significantly
      higher than in normal adjacent mucosa from the same patient. However, polyamine
      content was not significantly altered, suggesting dysregulation of the polyamine
      pathway. Flow cytometry is being used to assess the presence of aneuploidy and
      its significance in a premalignant lesion. Initial results have demonstrated that
      aneuploidy and dysplasia can be discordant. Cytogenetic analysis using short-term
      epithelial cultures established from endoscopic biopsies of the lesion has
      demonstrated the presence of clonal karyotypic abnormalities. The clinical
      significance of aneuploidy and abnormal karyotype, however, remains to be proved.
      Chemopreventive intervention trials have included use of 13-cis-retinoic acid.
      Considerable toxicity was encountered, and the lesion showed no change in extent
      in 11 evaluable patients. A subsequent clinical trial with a biologic endpoint
      used alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to
      test whether a low dose could produce changes in polyamine content in
      gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389697
TI  - Tumor antigen phenotype, biologic staging, and prognosis in head and neck
      squamous carcinoma.
AB  - Prior studies of alterations in tumor expression of normal blood group antigens
      and A9/alpha 6 beta 4 integrin, an extracellular matrix receptor, have suggested
      that these immunohistologic markers reflect the biologic aggressiveness of head
      and neck squamous carcinomas. To confirm these preliminary observations,
      prospective long-term follow-up of 82 previously untreated head and neck squamous
      carcinoma patients was performed. All patients were treated with conventional
      therapy. Median follow-up was 57 months. Tumor immunohistology for ABH blood
      group and A9/alpha 6 beta 4 integrin expression was performed and correlated with
      measures of host cellular immunity, disease-free survival, and overall survival.
      Loss of blood group expression and high A9/alpha 6 beta 4 integrin expression
      were each directly related to an increased frequency of early tumor recurrence.
      The combination of both variables was significantly associated with both disease
      free (P = .029) and overall survival (P = .05). Increased expression of A9/alpha
      6 beta 4 was associated with impaired T-lymphocyte function (P = .005), and loss
      of blood group expression was associated with decreased peripheral blood levels
      of CD8+ T-lymphocytes (P = .013). The findings suggest that these phenotypic
      characteristics of antigen expression in head and neck squamous carcinomas are
      important markers of biologically aggressive cancers and impaired host immune
      response. The clinical use of these biologic staging parameters in the initial
      assessment of patients should allow selection of more aggressive primary
      treatment strategies for individual patients.

PMID- 1389698
TI  - Regulation of expression and phosphorylation of A9/alpha 6 beta 4 integrin in
      normal and neoplastic keratinocytes.
AB  - The A9 antigen is a basement membrane antigen of normal squamous epithelial cells
      that is strongly expressed in many squamous carcinomas. High expression of this
      antigen is associated with early relapse in squamous cell carcinomas of the head
      and neck. We now know that the A9 antigen is structurally, immunologically, and
      functionally similar to the alpha 6 beta 4 integrin that has been shown to be
      linked to metastatic behavior in murine tumor models. The alpha 6 and beta 4
      genes have been cloned and sequenced, and a model has been constructed from the
      deduced amino acid composition. In this study we present a hypothetical model and
      use it to design experiments to assess the factors that influence the expression
      of the A9/alpha 6 beta 4 integrin in normal and malignant keratinocytes. High
      calcium induces down regulation of A9/alpha 6 beta 4 antigen in normal but not
      malignant keratinocytes within 24 hours. Although calcium can down-regulate beta
      4 message in tumor cells in the absence of epidermal growth factor (EGF),
      transcription of beta 4 increased in the tumor cells under the conditions we used
      for assessing antigen expression (calcium plus EGF). Retinoic acid also
      stimulated transcription of beta 4 in tumor cells, but this was partially
      inhibited by the presence of high calcium. Phosphorylation of the beta 4 chain
      was stimulated by epidermal growth factor and calcium in normal keratinocytes,
      but in the malignant cells phosphorylation was constant regardless of the culture
      conditions. Our results indicate that high expression of the alpha 6 beta 4
      integrin is associated with conditions that favor migration and undifferentiated
      proliferation of normal keratinocytes and that malignant keratinocytes differ
      from normal keratinocytes by constitutive phosphorylation of beta 4 and by
      failure to downregulate beta 4 transcription in response to calcium in the
      presence of EGF.

PMID- 1389699
TI  - Stress proteins, self defence, and the myocardium.

PMID- 1389700
TI  - Antiphospholipid antibodies and cardiovascular disease.

PMID- 1389701
TI  - Is VVI pacing outmoded?

PMID- 1389702
TI  - Impact of converting enzyme inhibition on progression of chronic heart failure:
      results of the Munich Mild Heart Failure Trial.
AB  - OBJECTIVE: Neurohormonal activation has major impact on the pathophysiology of
      congestive heart failure. The Munich Mild Heart Failure Trial was designed to
      test the hypothesis that interference with the renin-angiotensin system by
      angiotensin converting enzyme inhibition favourably influences the natural
      history of heart failure. DESIGN AND PATIENTS: 170 patients, median New York
      Heart Association (NYHA) class II, were randomised to double blind treatment with
      25 mg captopril twice a day or placebo in addition to standard treatment for a
      median observation period of 2.7 years. MAIN OUTCOME MEASURES: Progression of
      heart failure to NYHA class IV on an optimally adjusted standard treatment, death
      due to progressive heart failure, and sudden death. RESULTS: Heart failure
      progressed to class IV in nine patients (10.8%) treated with captopril and in 23
      patients (26.4%) treated with placebo (p = 0.01). The mean survival time until
      this end point was 223 days longer in the captopril group (Kaplan-Meier life
      table analysis; p = 0.02). Also, progressive deterioration to severe heart
      failure was a powerful predictor of total mortality and death from heart failure;
      80% of deaths due to progressive heart failure occurred after this end point.
      There were fewer deaths caused by progressive heart failure in the captopril
      group than in the placebo group (4 v 11; p = 0.10) but similar numbers of sudden
      deaths (11 v 10). Progressive heart failure was the cause of death in 18.2% of
      all deaths in the captopril group and 50% in the placebo group. Total heart
      failure events (the end point on which power calculation was based) were also
      more common in the placebo group (19 v 32 events) but not significantly so. Total
      mortality was similar to both groups (22 of 83 v 22 of 87). CONCLUSIONS:
      Angiotensin converting enzyme inhibition in conjunction with standard therapy
      early in the course of congestive heart failure slowed the progress of heart
      failure and thus favourably altered the natural history of the disease.

PMID- 1389704
TI  - Variable patterns of ST-T abnormalities in patients with left ventricular
      hypertrophy and normal coronary arteries.
AB  - BACKGROUND: Classically, the ST-T configuration in the electrocardiogram of
      patients with left ventricular hypertrophy is said to have a typical pattern of
      ST depression together with asymmetrical T wave inversion (the so-called left
      ventricular strain pattern). However, many patients with left ventricular
      hypertrophy may also have ischaemic heart disease. To revise the
      electrocardiographic criteria for left ventricular hypertrophy the ST-T
      configuration in patients with left ventricular hypertrophy documented by
      echocardiography and with normal coronary arteries was assessed. METHODS: 24
      patients were selected for this study. All had left ventricular hypertrophy
      documented by echocardiography, normal coronary arteries by cardiac
      catheterisation, and ST and/or T wave abnormalities in the lateral leads of their
      electrocardiogram. There were eight patients with aortic valve disease and 16
      with hypertension who had coronary angiography as part of an investigation into
      the risk factors of sudden cardiac death caused by hypertensive left ventricular
      hypertrophy. No patient was receiving digitalis preparations or had electrolyte
      disturbances, and none had a previous myocardial infarction or ventricular
      conduction defect. RESULTS: Typical electrocardiographic evidence of left
      ventricular strain was found in approximately two thirds (63%) of patients and
      95% of this subgroup had asymmetrical T wave inversion. Flat ST segment
      depression, with or without T wave inversion or isolated T wave inversion
      (symmetrical or asymmetrical) in the anterolateral leads, was seen in the
      remaining 37% of patients. CONCLUSIONS: These findings indicate that left
      ventricular hypertrophy without coronary artery disease can cause variable types
      of ST-T abnormalities in the anterolateral leads including the typical left
      ventricular strain pattern and non-specific ST-T changes. Non-specific
      abnormalities could not be distinguished from those of coronary artery disease
      and may adversely affect the accuracy of the electrocardiographic criteria for
      the diagnosis of left ventricular hypertrophy because they do not accord with the
      criteria for left ventricular strain.

PMID- 1389703
TI  - Limitations of transoesophageal echocardiography in patients with focal cerebral
      ischaemic events.
AB  - OBJECTIVE: To investigate the detection rate of cardiac sources of embolism by
      transoesophageal echocardiography in patients with focal cerebral ischaemic
      events and to relate the echocardiographic findings to other clinical findings.
      DESIGN: Prospective study with blinded analysis of the echocardiographic data and
      subsequent comparison with the other clinical findings. SETTING: Regional
      cardiothoracic unit based in a teaching hospital. PATIENTS: 131 consecutive
      patients with focal ischaemic cerebral events (49 with a transient ischaemic
      attack, 77 with a cerebrovascular accident, and five with a retinal arterial
      embolus) referred for echocardiography. INTERVENTIONS: Full M mode, cross
      sectional, Doppler, and contrast echocardiography by both the precordial and
      transoesophageal techniques. RESULTS: Precordial echocardiography detected a
      cardiac abnormality in 72 patients. Transoesophageal echocardiography confirmed
      all the precordial findings (except left ventricular hypertrophy, which at
      present cannot be defined with this technique) and detected other abnormalities
      in a further 20 patients (18 with potential right-to-left shunts and two with
      valve vegetations). It also showed spontaneous contrast echoes in 27 of 28
      patients with a large left atrium and showed atrial thrombus in three. Cardiac
      abnormalities were clinically detected in 53 patients, all of which were
      confirmed or documented by echocardiography. In the 78 patients with no
      clinically detectable cardiac abnormality six had mitral valve prolapse and one
      had a regional wall motion defect (identified by precordial echocardiography) and
      17 had potential right-to-left shunts (11 of which were identified only by
      transoesophageal echocardiography). CONCLUSIONS: Transoesophageal
      echocardiography is more sensitive than precordial echocardiography in detecting
      potential sources of embolism in these patients. However, except for the
      detection of a potential right-to-left shunt, the yield in patients with no
      cardiac abnormality is low. Moreover, the abnormalities detected in those with
      previously detected cardiac disease merely confirm the clinical diagnosis.
      Patients with left atrial spontaneous contrast echoes may benefit from
      anticoagulation but this requires further study. Until more data are available on
      this feature and on the role of potential right-to-left shunts in this
      population, the contribution of echocardiography, precordial or transoesophageal,
      remains limited.

PMID- 1389705
TI  - Negative extrathoracic pressure ventilation for phrenic nerve palsy after
      paediatric cardiac surgery.
AB  - OBJECTIVE: To investigate the feasibility of negative extrathoracic pressure
      ventilation as a respiratory support following phrenic nerve palsy after cardiac
      surgery. DESIGN: An uncontrolled pilot study. PATIENTS: 14 patients aged one week
      to 30 months (median 5.3 months) with phrenic nerve palsy diagnosed by phrenic
      nerve conduction tests and diaphragmatic electromyograms. Four had bilateral and
      10 unilateral palsy. Before treatment all required oxygen and 10 were receiving
      positive pressure ventilation. One of the patients with bilateral and four of the
      patients with unilateral palsies had undergone a plication before negative
      pressure ventilation was started. INTERVENTION: Treatment was started 6-65 days
      (median 23) after operation with a newly designed system which included a Perspex
      chamber, which gave easy access to the child, and an elastic latex neck seal.
      Continuous negative pressure was used in conjunction with intermittent positive
      pressure ventilation while continuous or intermittent negative pressure
      ventilation was used in extubated infants. RESULTS: All four patients with
      bilateral palsy survived with long-term intermittent negative pressure
      ventilation and did not require further surgery. Of the 10 with unilateral
      lesions, seven required no further surgery, two underwent plication, and one had
      a re-plication. Three patients with unilateral palsy died of non-respiratory
      causes. The duration of positive pressure ventilation after starting negative
      pressure ranged from 0 to 23 days (median 6). Treatment with negative pressure
      lasted for 3-241 days (median 32) and was predominantly administered off the
      intensive care unit, including at home. CONCLUSIONS: Negative pressure
      ventilation may be an alternative to positive airway pressure ventilation in the
      management of phrenic nerve palsy. A multicentre randomised controlled trial is
      now required to assess further the role of negative pressure ventilation in
      phrenic nerve palsy.

PMID- 1389707
TI  - Morphological study of defects of the atrial septum within the oval fossa:
      implications for transcatheter closure of left-to-right shunt.
AB  - OBJECTIVE: To determine the anatomical variability of the oval fossa in cases of
      atrial septal defect and to find out which factors might make such defects
      suitable or unsuitable for closure by umbrella or clamshell devices. DESIGN: 100
      specimens with defects of the atrial septum within the oval fossa were studied,
      especially the position of the defects within the fossa; the area of the defect
      in relation to the total area of the oval fossa; the shape of the rims and flap
      valve of the oval fossa; and the anatomical variability in the eustachian and
      thebesian valves. RESULTS: The oval fossa was displaced to the mouth of the
      inferior caval vein in four cases; displaced to the mouth of superior caval vein
      in two cases; placed on the middle of the interatrial wall in 43; or placed
      slightly towards the inferior caval vein in 51. Because of their shape 29 of the
      hearts were considered to be unsuitable for transcatheter closure of the defect.
      This was because the defect was too large (16 hearts); the oval fossa was
      displaced to the mouth of the inferior caval vein (four hearts) or to the
      superior caval vein (two hearts); lacked its anterior rim (two hearts); lacked
      the posteroinferior rim (one heart); because a thick eustachian valve was
      displaced posteriorly forming a false posteroinferior rim (one heart); or because
      the strand of insertion of the floor of the oval fossa was too distant from the
      left atrial aspect (three hearts). CONCLUSION: 68 hearts appeared to be ideal
      candidates for transcatheter closure; 3 would probably have been suitable; but 29
      were unsuitable. These morphological variations might explain why the procedure
      has been unsuccessful in so many cases. Patients should be screened before any
      attempt is made at transcatheter closure.

PMID- 1389706
TI  - Cross sectional and Doppler echocardiographic evaluation of aortopulmonary
      shunts.
AB  - BACKGROUND: Shunt vessels were imaged and shunt flow was analysed by cross
      sectional and Doppler echocardiography in 12 patients who had had 14 shunt
      procedures (nine left Blalock-Taussig shunts, three right Blalock-Taussig shunts,
      one modified Waterston shunt, and one central shunt). METHODS: The shunt vessels
      were classified by echocardiography as uniformly patent, segmentally stenosed,
      and uniformly stenosed. These findings were compared with those of angiography.
      Also the peak flow velocities at the aortic and the pulmonary ends of the shunt
      vessels were measured by Doppler echocardiography and the ratio of these values
      was calculated for each shunt. RESULTS: Twelve (85.7%) of 14 shunt vessels were
      imaged along their entire length by cross sectional echocardiography. The two
      remaining shunt vessels were only partially imaged. In 10 patients who also had
      angiography the echocardiographic and angiographic images of the shunt vessels
      were identical. The ratio of the peak flow velocity measured at the aortic and
      the pulmonary ends of the shunt vessel was significantly larger in the
      segmentally stenosed shunt vessels than in the uniformly patent shunt vessels (p
      < 0.001). The ratio in the two shunt vessels only partially imaged by cross
      sectional echocardiography indicated that they were segmentally stenosed.
      CONCLUSION: The combination of cross sectional and Doppler echocardiography may
      be useful for determining either the patency or the morphology of an
      aortopulmonary shunt.

PMID- 1389708
TI  - Severe haemolysis after transcatheter duct occlusion: a non-surgical remedy.
AB  - Severe mechanical haemolysis occurred in a seven month old infant after the
      insertion of a 17 mm Rashkind double umbrella device. The placement of a second
      device 23 days after the initial procedure abolished haemolysis.

PMID- 1389709
TI  - Spontaneously acquired fistula from the right coronary artery to the right
      ventricular cavity.
AB  - A 47 year old man developed a fistula from the right ventricular branch of the
      right coronary artery to the right ventricular cavity in association with distal
      occlusion of the main trunk of the right coronary artery. There was no clinical
      or electrocardiographic evidence of acute myocardial infarction.

PMID- 1389710
TI  - Recommended guidelines for uniform reporting of data from out-of-hospital cardiac
      arrest (new abridged version). The "Utstein style". The European Resuscitation
      Council, American Heart Association, Heart and Stroke Foundation of Canada, and
      Australian Resuscitation Council.

PMID- 1389711
TI  - Mortality within hospital after resuscitation from ventricular fibrillation
      outside hospital.
AB  - OBJECTIVE: To determine factors related to mortality within hospital after
      successful resuscitation from ventricular fibrillation outside hospital by a
      mobile coronary care unit manned by a physician. DESIGN: Retrospective review of
      records of patients resuscitated and admitted to hospital between 1 January 1966
      and 31 December 1987. SETTING: Mobile coronary care unit, coronary care unit, and
      cardiology department. PATIENTS: 281 patients (227 male), aged 14-82 (mean 58)
      successfully resuscitated from ventricular fibrillation outside hospital of whom
      182 (65%) developed ventricular fibrillation before the arrival of the mobile
      coronary care unit. The aetiology of ventricular fibrillation was acute
      myocardial infarction in 194 patients (69%), ischaemic heart disease without
      infarction in 71 (25%), and other or unknown in 16 (6%). MAIN OUTCOME MEASURES:
      Death within hospital. RESULTS: There were 91 deaths in hospital (32%). Factors
      on univariate analysis significantly associated with increased mortality were
      patient age > or = 60 years, previous myocardial infarction or cerebrovascular
      disease, prior digoxin or diuretic treatment, collapse without prior chest pain
      or with pain lasting 30 minutes or less, defibrillation delayed by > or = 5 min,
      > or = four shocks required to correct ventricular fibrillation, left ventricular
      failure or pulmonary oedema and cardiogenic shock after successful
      defibrillation, and coma on admission to hospital. On multivariate analysis the
      most important factors (in rank order) were cardiogenic shock after
      defibrillation, coma on admission to hospital, age > or = 60 years and the
      requirement for four or more shocks to correct ventricular fibrillation.
      CONCLUSIONS: The in-hospital mortality of patients resuscitated from ventricular
      fibrillation outside hospital was related to patient characteristics before the
      cardiac arrest and to the immediate haemodynamic and neurological status after
      correction of ventricular fibrillation as well as to factors at the resuscitation
      itself. The in-hospital mortality of this study compares favourably with the
      results obtained by units staffed by paramedical workers and emergency medical
      technicians, although 35% (99/281) of the patients had ventricular fibrillation
      after the arrival of the mobile unit and defibrillation was thus rapid.

PMID- 1389712
TI  - Insulin resistance, diabetes, and risk markers for ischaemic heart disease in
      Asian men and non-Asian in Bradford.
AB  - OBJECTIVE: To examine the hypothesis, in a community not studied before, that
      insulin resistance associated with centralised adiposity is the mechanism
      underlying the predisposition of Asian immigrant communities to both ischaemic
      heart disease and diabetes mellitus. DESIGN: Cross sectional study within one
      socioeconomic stratum. SETTING: Two factories in the textile sector in Bradford,
      West Yorkshire. SUBJECTS: Male manual workers of Asian (110) and non-Asian origin
      (156) aged 20-65 years. RESULTS: Diabetes was almost three times more prevalent
      in the Asian group. Two hours after an oral glucose load Asian men had double the
      serum insulin concentrations of non-Asian men (p < 0.0001). Asian men also had
      significantly lower concentrations of plasma total cholesterol (p < 0.03), high
      density lipoprotein cholesterol (HDL) (HDL2, p < 0.0001; HDL3, p < 0.0001), and
      apolipoprotein AI (p < 0.0001). Fasting plasma triglyceride concentrations were
      slightly higher (p = 0.072) in the Asian men; thus the ratio of triglyceride
      cholesterol was higher (p = 0.006). The inter-relation between serum insulin and
      plasma lipid concentrations indicated metabolic differences between the ethnic
      groups. Insulin concentrations were associated with cholesterol concentrations in
      the Asian men only and there was a lack of association between triglyceride, low
      density lipoprotein cholesterol, and HDL cholesterol in this group. The risk
      marker profile in the Asian men was therefore quite different to that of their
      non-Asian counterparts and was associated with a greater tendency to centralised
      adiposity. CONCLUSION: These data support the insulin resistance hypothesis and
      thus have important implications for strategies for the prevention of heart
      disease in Asian communities in the United Kingdom.

PMID- 1389713
TI  - Strenuous exercise, plasma fibrinogen, and factor VII activity.
AB  - OBJECTIVE: To assess the effect of physical activity on plasma fibrinogen and
      factor VII activity and thus on the risk of ischaemic heart disease. DESIGN:
      Cross sectional survey. SETTING: Ten group practices in the Medical Research
      Council's General Practice Research Framework. PATIENTS: 3967 men aged 45-69
      attending screening clinics for the thrombosis prevention trial. METHODS:
      Structured interview to elicit the intensity and frequency of physical exercise
      during past month. Measurement of fibrinogen, factor VII activity, cholesterol
      concentration, blood pressure, and other indices of ischaemic heart disease risk.
      RESULTS: Strenuous exercise was associated with significantly lower fibrinogen
      concentrations than mild exercise, implying a difference of about 15% in the risk
      of ischaemic heart disease. Strenuous exercise was also associated with lower
      cholesterol concentrations. More frequent strenuous exercise was associated with
      lower factor VII activity. CONCLUSIONS: With the recognition of plasma fibrinogen
      as a strong index of ischaemic heart disease risk the results of this and other
      studies suggest a pathway through which the protective effect of strenuous
      exercise may partly be mediated and they provide doctors and patients with a
      valuable incentive towards prevention, particularly in those whose risk of
      ischaemic heart disease is substantially due to raised fibrinogen concentrations.

PMID- 1389714
TI  - Comparative electrophysiological effects of captopril or hydralazine combined
      with nitrate in patients with left ventricular dysfunction and inducible
      ventricular tachycardia.
AB  - OBJECTIVE: To assess the electrophysiological and antiarrhythmic effects of
      pharmacological load manipulation by an angiotensin converting enzyme (ACE)
      inhibitor (captopril) and a direct vasodilator (hydralazine plus isosorbide
      mononitrate) in patients with inducible ventricular tachycardia and impaired left
      ventricular function. DESIGN: Randomised open label cross-over comparison of
      three regimens. SETTING: Tertiary arrhythmia referral centre. SUBJECTS: Eight
      patients with reduced left ventricular function and sustained ventricular
      tachycardia inducible by programmed stimulation. INTERVENTIONS: Three treatment
      regimens each of 48 hours duration: captopril, hydralazine plus isosorbide
      mononitrate, and control (no vasodilator). MAIN OUTCOME MEASURES: Changes in
      central haemodynamics, electrophysiological parameters, and induction of
      ventricular tachycardia during treatment with captopril, or hydralazine combined
      with nitrate, compared with a control period. RESULTS: Both vasodilator
      treatments produced similar balanced reductions in peak systolic pressures and
      filling pressures compared with controls. Captopril had no effect on sinus cycle
      length, atrial refractoriness, or intraventricular conduction, but prolonged
      ventricular effective and functional refractory periods and QT interval during
      constant rate atrial pacing. Hydralazine combined with nitrate did not
      significantly alter any electrophysiological variable. Ventricular tachycardia
      was similarly inducible during all three periods. CONCLUSIONS: Load manipulation
      by captopril but not hydralazine combined with nitrate prolonged ventricular
      refractoriness and repolarisation, possibly reflecting a combination of mechano
      electrical effect with the restraining influence of ACE inhibitors on reflex
      sympathetic stimulation.

PMID- 1389715
TI  - Role of atrial contraction and synchrony of ventricular contraction in the
      optimisation of ventriculoarterial coupling in humans.
AB  - OBJECTIVE: To examine the effects of pacing modes on the interaction between the
      left ventricle and arterial system in humans. DESIGN: The slope of the end
      systolic pressure-volume relation (end systolic elastance), effective arterial
      elastance, the ratio of effective arterial elastance to end systolic elastance,
      and mechanical energy efficiency were compared under different pacing modes
      (atrial, atrioventricular, and ventricular). PATIENTS: Nine male patients with
      sick sinus syndrome who had cardiac catheterisation for diagnosis and to see
      whether they needed a pacemaker. INTERVENTIONS: A conductance catheter with tip
      manometer was inserted into the left ventricle to obtain pressure-volume loops,
      and two pacing catheters were inserted into the right atrium and into the right
      ventricle respectively. RESULTS: End systolic elastance was lower in
      atrioventricular pacing than in atrial pacing, but effective arterial elastance
      was not significantly different. End systolic elastance was lower in ventricular
      pacing than in atrioventricular pacing, and effective arterial elastance was
      higher in ventricular pacing than in atrioventricular pacing. Consequently the
      ratio of effective arterial elastance to end systolic elastance was lowest in
      atrial pacing and highest in ventricular pacing, and mechanical energy efficiency
      was highest in atrial pacing and lowest in ventricular pacing. CONCLUSIONS:
      Atrial contraction and synchronous ventricular contraction independently optimise
      ventriculoarterial coupling in terms of a transfer of energy. Thus atrial pacing
      gives the best ventriculo-arterial coupling among these pacing modes.

PMID- 1389716
TI  - Changes in myocardial echo amplitude during reversible ischaemia in humans.
AB  - OBJECTIVE: This study investigated the changes in regional myocardial ultrasonic
      backscatter, measured as myocardial echo amplitude, that occur during reversible
      myocardial ischaemia in humans. DESIGN: Left anterior descending coronary
      angioplasty was used to produce reversible myocardial ischaemia in human
      subjects. Regional myocardial echo amplitude was studied in the interventricular
      septum and left ventricular posterior free wall before, during, and after
      coronary occlusion with the angioplasty balloon. Wall motion analysis of the left
      ventricle was performed from simultaneous cross sectional echocardiographic
      imaging. Patients were studied prospectively. PATIENTS: Six patients (mean age 56
      (SD 11), range 46 to 69 years) with single vessel, left anterior descending
      coronary artery stenoses, were investigated during elective coronary angioplasty.
      A total of 11 balloon inflations were studied. SETTING: All patient studies were
      performed at Harefield Hospital. Echo amplitude analysis was performed at the
      Royal Brompton Hospital. INTERVENTIONS: Angioplasty was performed by the usual
      procedure at Harefield Hospital for elective coronary angioplasty. All routine
      medication including beta blockers and calcium antagonists were continued.
      Inflation pressures were up to 12 atm (1212 kPa) and mean inflation time ranged
      from 30 to 120 (86 (31)) s. In four studies the first inflation was examined, in
      three the second, in two the third, and in one each the fourth and fifth
      inflations. Echo amplitude and cross sectional echo-cardiographic studies were
      recorded with a 3.5 MHz Advanced Technology Laboratories (ATL) (720A/8736 series)
      mechanical sector scanner and an ATL Mark III (860-1 series) echocardiograph
      system with 45 dB logarithmic grey scale compression. MAIN OUTCOME MEASURES:
      Regional echo amplitude was examined in four regions of the left ventricle-
      namely, the basal and mid-septum, and basal and mid-posterior wall. Consecutive
      end diastolic and end systolic frames were analysed and cyclic variation was
      determined as the difference between the level of echo amplitude at end diastole
      and at end systole. Measurements were made before balloon inflation, at peak
      inflation, and after balloon deflation. Regional wall motion and systolic wall
      thickening were analysed qualitatively. RESULTS: Before balloon inflation, cyclic
      variation in echo amplitude was noted in all regions (basal septum, 2.4 (SD 1.1)
      dB; mid-septum, 2.5 (1.1) dB; basal posterior wall, 3.3 (2.1) dB; mid-posterior
      wall, 3.9 (1.6) dB). During balloon inflation there was a significant fall in
      cyclic variation to 0.4 (0.9) dB (p < 0.0002) in the mid-septum. This was
      predominantly owing to an increase in end systolic echo amplitude from 5.4 (2.0)
      dB to 9.3 (1.9) dB (p < or = 0.01). This was associated with the development of
      severe hypokinesis or akinesis in the mid-septum. No significant changes in echo
      amplitude occurred in the three other regions examined. Changes were completely
      reversed after balloon deflation. CONCLUSIONS: These results suggest a causal
      relation between occlusion of the supplying coronary artery and blunting of
      myocardial echo amplitude cyclic variation. It is suggested that balloon
      occlusion produced myocardial ischaemia. The resultant impairment of myocardial
      contraction then caused a blunting of cyclic variation in echo amplitude. The
      results of this study provide further data about the ability of quantitative
      studies of ultrasonic backscatter to identify alterations in the myocardium
      during injury.

PMID- 1389717
TI  - Symptomatic and silent myocardial ischaemia in hypertensive patients with left
      ventricular hypertrophy.
AB  - OBJECTIVE: To assess the prevalence of symptomatic and silent myocardial
      ischaemia in patients with hypertensive left ventricular hypertrophy. DESIGN:
      Cross sectional study. SETTING: University department of medical cardiology.
      PATIENTS: 90 patients (68 men and 22 women; mean age 57 (range 25 to 79)) with
      left ventricular hypertrophy due to essential hypertension. INTERVENTIONS: 48
      hour ambulatory ST segment monitoring (all patients), exercise
      electrocardiography (n = 79), stress thallium scintigraphy (n = 80), coronary
      arteriography (n = 35). RESULTS: 43 patients had at least one episode of ST
      segment depression on ambulatory electrocardiographic monitoring. The median
      number of episodes was 16 (range 1 to 84) with a median duration of 8.6 (range 2
      to 17) min. Over 90% of these episodes were clinically silent. 26 patients had
      positive exercise electrocardiography and 48 patients had reversible thallium
      perfusion defects despite chest pain during exercise in only five patients. 18 of
      the 35 patients who had coronary arteriography had important coronary artery
      disease. Seven of these patients gave no history of chest pain. CONCLUSIONS:
      Symptomatic and silent myocardial ischaemia are common in hypertensive patients
      with left ventricular hypertrophy, even in the absence of epicardial coronary
      artery disease.

PMID- 1389718
TI  - Circulating endothelin in acute ischaemic syndromes.
AB  - BACKGROUND: Endothelin is an extremely potent vasoconstrictor that may have a
      role in the pathogenesis of acute myocardial ischaemia. Atrial natriuretic factor
      is an endogenous antagonist of endothelin. To find the pattern and possible
      importance of circulating endothelin in ischaemic heart disease, concentrations
      in normal controls and those in patients with stable and unstable angina, acute
      myocardial infarction, and chronic cardiac failure were compared. The relation
      between circulating concentrations of endothelin and atrial natriuretic factor in
      the aftermath of myocardial infarction was also examined. METHODS: Eighteen
      patients with acute myocardial infarction, 10 with unstable angina, 10 with
      stable angina, 12 with chronic cardiac failure, and 10 normal controls were
      studied. Endothelin concentration was measured in venous plasma by
      radioimmunoassay. In patients with acute myocardial infarction simultaneous
      concentrations of endothelin and atrial natriuretic factor were measured on
      admission and at one, four, and 24 hours. RESULTS: Mean concentrations (SEM) of
      endothelin were 5.72 (0.19) fmol/ml in controls, 6.56 (0.48) fmol/ml in stable
      angina, 6.41 (0.48) fmol/ml in unstable angina, and 13.83 (0.95) fmol/ml in
      chronic cardiac failure. In acute myocardial infarction concentrations were 8.81
      (0.69) fmol/ml on admission, 11.85 (1.02) fmol/ml at one hour, 11.88 (1.10)
      fmol/ml at four hours, and 7.30 (0.49) fmol/ml at 24 hours. Concentrations of
      atrial natriuretic factor at the same times were 68.1 (13.1) pg/ml, 8.4 (1.5)
      pg/ml, 24.4 (4.1) pg/ml, and 42.0 (6.9) pg/ml. CONCLUSIONS: Plasma endothelin is
      raised in chronic heart failure and in the aftermath of acute myocardial
      infarction but not in stable or unstable angina. After myocardial infarction
      endothelin concentrations are raised whereas concentrations of atrial natriuretic
      factor are relatively low. The role of endothelin in the pathogenesis of acute
      myocardial infarction and its interactions with other humoral factors require
      further investigation.

PMID- 1389719
TI  - Emergency coronary artery surgery after refractory cardiac arrest: a single
      centre experience.
AB  - OBJECTIVE: To determine the incidence and outcome of refractory cardiac arrest
      necessitating emergency coronary artery bypass grafting. DESIGN: Retrospective
      survey of cardiac catheterisation and surgical records. SETTING: The London Chest
      Hospital. PATIENTS: All patients requiring emergency coronary artery bypass
      grafting after cardiovascular collapse in the catheterisation suite between
      January 1984 and December 1989. MAIN OUTCOME MEASURES: Incidence of refractory
      cardiac arrest in the study group and perioperative mortality. RESULTS: Thirteen
      of 8675 patients undergoing coronary arteriography or angioplasty had refractory
      cardiac arrests. Five patients died, but the remainder survived to be discharged
      from hospital without serious morbidity. CONCLUSION: Without immediate surgical
      intervention the mortality for these 13 patients would have been 100%.

PMID- 1389720
TI  - Predictors of risk in patients with unstable angina admitted to a district
      general hospital.
AB  - OBJECTIVE: To observe the long-term prognosis of patients with unstable angina
      and select simple criteria to identify high and low risk subgroups. DESIGN: A six
      month prospective survey with three year follow up. SETTING: One eleven bed
      coronary care unit. PATIENTS: All patients admitted with chest pain in whom no
      infarct was confirmed by subsequent electrocardiographic or enzyme changes and
      for whom no alternative cause of chest pain was found were studied. Unstable
      angina was also diagnosed if there was evidence of myocardial ischaemia in the
      form of previous effort angina, previous myocardial infarction, or if transient
      electrocardiographic changes accompanied the pain. When none of the above were
      present, chest pain without a known cause, was diagnosed. INTERVENTIONS: No
      routine intervention. Angiography and revascularisation for persistent symptoms
      despite medical treatment. OUTCOME MEASURES: Death or non-fatal infarction.
      RESULTS: In the 141 patients with unstable angina there were eight deaths and
      five non-fatal infarctions during the first eight weeks. Symptoms of increasing
      angina before admission were similar in all three groups and did not help predict
      early complications. Recurrence of pain in hospital, a rise in cardiac enzymes to
      less than twice the upper limit of normal, and transient electrocardiographic
      changes were all associated with an increased risk of early events. The presence
      of either abnormal enzyme activity or more than five episodes of pain in hospital
      identified a group of 49 in whom 11 of the 13 early events occurred. After three
      years, 29 of the 141 patients had died and eight had had infarctions (overall
      event rate 26%). Seventeen had undergone revascularisation (12%) and 51 (36%)
      were on antianginal treatment. Thirty six (26%) were still alive, without new
      myocardial infarction, and were free of angina. In the 29 patients with chest
      pain without a known cause there were no early events and only one non-fatal
      infarction during the three year follow up. CONCLUSION: When patients are
      admitted to the coronary care unit with chest pain not due to myocardial
      infarction, the history, electrocardiography and measurement of cardiac enzymes
      are sufficient to identify high and low risk subgroups.

PMID- 1389721
TI  - Atrial myxoma: tumour or trauma?
AB  - A mass lesion developed in the right atrium at the site of a trans-septal
      puncture after percutaneous balloon dilatation of the mitral valve in a man aged
      74. The lesion had the pathological appearance of an atrial myxoma and seemed to
      have developed after trauma to the intra-atrial septum. This case suggests that
      at least some atrial myxomas are reactive rather than neoplastic in origin.

PMID- 1389722
TI  - Endocarditis with aneurysm involving an aortic homograft used to correct a
      truncus arteriosus: medical-surgical salvage.
AB  - An aneurysm of an aortic homograft conduit, used to correct a type I truncus
      arteriosus anomaly in a four month old infant, developed when the patient was 15.
      Blood cultures grew Staphylococcus aureus. The aneurysm was detected by magnetic
      resonance imaging and digital subtraction angiocardiography. An emergency open
      heart operation, guided by these investigations, was performed to remove the
      original homograft and replace it with another valved aortic homograft.
      Postoperative antibiotic treatment had to be stopped when profound neutropenia
      developed. This responded to treatment with recombinant human granulocyte colony
      stimulating factor. Three years later she was symptom free and did not require
      medication. Chest x rays and echocardiograms showed a normally functioning heart
      and conduit valve.

PMID- 1389723
TI  - Coronary heart disease in Indians, Pakistanis, and Bangladeshis: aetiology and
      possibilities for prevention.

PMID- 1389724
TI  - Working party report on cardiac rehabilitation.

PMID- 1389725
TI  - Immunoglobulin response to intravenous streptokinase in acute myocardial
      infarction.

PMID- 1389726
TI  - Myocardial ischaemia and ventricular arrhthymias precipitated by physiological
      concentrations of adrenaline in patients with coronary artery disease.

PMID- 1389728
TI  - Novel exercise protocol suitable for use on a treadmill or a bicycle ergometer.

PMID- 1389727
TI  - Cyclosporin treatment and nitric oxide release in human coronary arteries.

PMID- 1389729
TI  - Extending the use of autologous arterial conduits in myocardial
      revascularisation.

PMID- 1389730
TI  - Pacemaker syndrome: an iatrogenic condition.

PMID- 1389731
TI  - Monitoring of streptokinase resistance titre in acute myocardial infarction
      patients up to 30 months after giving streptokinase or anistreplase and related
      studies to measure specific antistreptokinase IgG.
AB  - OBJECTIVE: To examine the induction of antistreptokinase antibodies after giving
      streptokinase or anistreplase to patients with acute myocardial infarction.
      DESIGN: Patients were randomly allocated to receive either 1.5 x 10(6) IU,
      streptokinase or 30U anistreplase in a double blind study. Blood samples were
      collected immediately before treatment and subsequently at intervals up to 30
      months; plasma samples were assayed for streptokinase resistance titre
      (functional assay) and streptokinase binding by IgG (microradioimmunoassay).
      SETTING: Cardiology department in a general hospital. PATIENTS: 128 consecutive
      eligible patients. Samples were collected for up to one year according to a
      prospective design: a subsection of 47 patients was selected for intensive study
      over the first 14 days. After one year, all available patients (67) were sampled
      on one further occasion. RESULTS: Antibody responses to streptokinase and
      anistreplase were similar. Streptokinase resistance titres exceeded pretreatment
      concentrations five days after dosing, and values peaked at 14 days. By 12 months
      after dosing, 92% of resistance titres (n = 84) had returned to within the
      pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline
      concentrations within five days and peaked at 14 days. Half of the individual
      values had returned to within the pretreatment range by 12 months (n = 84) and
      89% by 30 months (n = 18). CONCLUSION: Although we cannot be sure of the clinical
      significance, because of the increased likelihood of resistance due to
      antistreptokinase antibody, streptokinase and anistreplase may not be effective
      if administered more than five days after an earlier dose of streptokinase or
      anistreplase, particularly between five days and 12 months, and increased
      antistreptokinase antibody may increase the risk of allergic-type reactions.

PMID- 1389732
TI  - Streptokinase induced defibrination assessed by thrombin time: effects on
      residual coronary stenosis and left ventricular ejection fraction.
AB  - OBJECTIVE: To evaluate laboratory markers of defibrination early after
      thrombolytic therapy and to determine their relation to residual stenosis and
      left ventricular ejection fraction measured angiographically before discharge
      from hospital. DESIGN: Prospective analysis of defibrination after streptokinase
      measured by fibrinogen assay and thrombin time to provide a comparison of these
      coagulation variables for predicting angiographic responses to treatment in
      patients with acute myocardial infarction. SETTING: The coronary care unit of a
      district general hospital. PATIENTS: 44 patients with acute myocardial infarction
      treated by streptokinase infusion, all of whom underwent paired blood sampling
      before and one hour after streptokinase and cardiac catheterisation at a median
      of six (interquartile range 3-9) days later. MAIN OUTCOME MEASURES: Assay of
      thrombin time and plasma fibrinogen concentrations one hour after streptokinase
      infusion. Relations between these coagulation variables and residual stenosis in
      the infarct related coronary artery and left ventricular ejection fraction.
      Separate analyses are presented for all patients (n = 44) and those with patency
      of the infarct related artery (n = 35). RESULTS: Streptokinase infusion produced
      profound defibrination in every patient as shown by changes in thrombin time and
      circulating fibrinogen. Thrombin time after streptokinase infusion correlated
      significantly with both residual stenosis (r = -0.43, p < 0.005) and left
      ventricular ejection fraction (r = 0.38, p < 0.02). The importance of these
      correlations was emphasised by the interquartile group comparison which showed
      that a thrombin time > or = 49 seconds predicted a residual stenosis of 74% and
      an ejection fraction of 65%, compared with 90% and 49% for a thrombin time < or =
      31 seconds (p < 0.01). When the analysis was restricted to patients with patency
      of the infarct related artery, the correlation between thrombin time and residual
      stenosis remained significant and group comparisons continued to show that
      patients in the highest quartile range had more widely patent arteries and better
      preservation of ejection fraction. Analysis of the fibrinogen data, on the other
      hand, showed insignificant or only marginally significant correlations with these
      angiographic variables. CONCLUSIONS: Early after streptokinase infusion for acute
      myocardial infarction, the level of defibrination measured by thrombin time has
      an important influence on residual coronary stenosis and left ventricular
      ejection fraction at discharge from hospital, values above 49 seconds being
      associated with the best angiographic result.

PMID- 1389733
TI  - Early and long term results of re-operation for coronary artery disease.
AB  - OBJECTIVE: To define the incidence, possible causes, operative procedure, and
      early and medium term results of patients undergoing reoperation for coronary
      artery disease. DESIGN: A retrospective analysis of patients undergoing
      reoperation in one hospital during a 10 year period. SETTING: A regional
      cardiothoracic centre. PATIENTS: 115 patients had reoperation for recurrent
      angina, 1-17 years (mean (SD) 7.4 (3.9)) after primary revascularisation. MAIN
      OUTCOME MEASURES: They received 279 grafts (2.4 grafts per patient); 58% of the
      grafts were anasatomosed to previously grafted vessels. The internal mammary
      artery was used in 87% of patients who required grafts to the left anterior
      descending coronary artery. RESULTS: Reoperation accounted for 8.3% of the total
      number of patients who underwent coronary bypass grafting. Graft failure alone or
      in combination with other factors was judged to be the cause of recurrence of
      symptoms in 87%. 42% of patients had two or more coronary risk factors. The early
      mortality was 5.2% and the actuarial survival at five and 10 years was 90.4% and
      88.4% respectively. 85% of the survivors had initial complete relief of angina
      and 14% had partial improvement. Freedom from recurrent symptoms at five and 10
      years was 66.6% and 34.6% respectively. CONCLUSIONS: Vein graft failure either
      alone or in combination with progression of native coronary disease is the main
      cause for symptomatic deterioration after bypass grafting. Reoperation can be
      performed with slightly increased risk and can give good early and medium term
      results.

PMID- 1389735
TI  - Jugular venous 'a' wave in pulmonary hypertension: new insights from a Doppler
      echocardiographic study.
AB  - OBJECTIVE: To study the mechanisms underlying the dominant 'a' wave seen in
      patients with primary pulmonary hypertension. DESIGN: Retrospective and
      prospective examination of the jugular venous pulse recording, flow in the
      superior vena cava, and Doppler echocardiographic studies. SETTING: A tertiary
      referral centre for both cardiac and pulmonary disease, with facilities for
      invasive and non-invasive investigation, and assessment for heart and heart-lung
      transplantation. PATIENTS: 12 patients with primary pulmonary hypertension, most
      being considered for heart-lung transplantation. RESULTS: Two distinct patterns
      of venous pulse and superior vena caval flow were identified: a dominant 'a' wave
      with no 'v' wave, an absent or poorly developed 'y' descent, and exclusively
      systolic downward flow in the superior vena cava (group 1, n = 8), and a dominant
      'v' wave, deep 'y' descent and exclusively diastolic downward flow in the
      superior vena cava (group 2, n = 4). A comparison between the two groups showed
      age (mean (SD)) 42 (18) v 36 (7) years, RR interval 700 (65) v 740 (240) ms, left
      ventricular end diastolic dimension 3.6 (0.8) v 3.2 (1.0) cm and end systolic
      dimension 2.1 (0.5) v 2.3 (0.3) cm, right ventricular end diastolic dimension 2.6
      (0.5) v 2.8 (0.6) cm, and pressure drop between right ventricle and right atrium
      60 (8) v 70 (34) mm Hg to be similar. Duration of tricuspid regurgitation 520
      (30) v 420 (130) ms and the time interval of pulmonary closure to the end of the
      tricuspid regurgitant signal 140 (30) v 110 (40) ms were longer in group 1
      compared with group 2, whereas right ventricular filling time was much shorter
      180 (70) v 350 (130) ms. In seven patients from group 1, a single peak of forward
      tricuspid flow was present, but this pattern was seen in only one patient from
      group 2. CONCLUSION: In patients with primary pulmonary hypertension, the
      apparent 'a' wave seen in the venous pulse is, in fact, a summation wave. It is
      probably the result of large pressure changes that must underlie rapid
      acceleration and deceleration of blood across the tricuspid valve when the right
      ventricular filling time is short.

PMID- 1389734
TI  - Influence of power and aerobic exercise training on haemostatic factors after
      coronary artery surgery.
AB  - OBJECTIVES: To determine the effects of aerobic and power exercise training on
      haemostatic factors after coronary artery surgery and to compare the effect of
      the two exercise programmes. DESIGN: A prospective randomised controlled study of
      six months aerobic and power exercise training in men after coronary artery
      surgery. SETTING: Exercise rehabilitation classes in a teaching hospital in
      Glasgow. PATIENTS: 55 men within 12 months of coronary artery surgery recruited
      from surgical centres and medical clinics and asked to participate in the study.
      INTERVENTIONS: Assessments, including a treadmill test, measurements of
      haemoglobin, platelet, fibrinogen, factor VIIc, and fibrinopeptide A
      concentrations, and packed cell volume, done at baseline, three months, and six
      months. Patients in the two exercise groups attended training sessions three
      times weekly for six months. Control patients had no formal exercise training but
      continued with their leisure time activities. MAIN OUTCOME MEASURES: Exercise
      performance on a treadmill, haematology, and haemostatic factor assays at
      baseline, three months, and six months. RESULTS: In the aerobic trained group
      exercise performance increased significantly over baseline at three months
      (interval change 146.7, 95% confidence interval (95% CI) 52.5 to 240.9 s, p =
      0.003) and was maintained at six months (interval change 172.1, 95% CI 63.3 to
      280.9 s, p = 0.002). In the power trained groups significant improvement in
      exercise performance was delayed until six months (interval change 99.9 s, 95% CI
      20.3 to 170.5 s, p = 0.01). Exercise performance in the control did not change
      significantly. Haemoglobin, concentration, packed cell volume, and platelet
      counts did not change significantly at any time. Fibrinogen concentration was
      significantly lower in the aerobic group than the other two groups at three
      months (2.96 g/dl compared with 3.3 g/dl and 3.87 g/dl in the power and control
      groups, p = 0.01). The power group had a lower fibrinogen concentration than the
      control group (p = 0.04). The lower fibrinogen concentration in the aerobic group
      was maintained at six months. There was a gradual rise in factor VIIc
      concentrations in the aerobic and control groups compared with a small fall in
      the power group. Fibrinopeptide A concentrations showed no consistent changes.
      CONCLUSIONS: Aerobic exercise training after coronary artery surgery causes an
      early favourable change in treadmill performance and in fibrinogen
      concentrations, that is maintained with further training. Power exercise training
      causes delayed benefit in treadmill performance. It also causes a small fall in
      fibrinogen concentrations. These changes may be relevant in reducing
      cardiovascular morbidity from graft failure and occurrence of myocardial
      infarction after coronary artery surgery.

PMID- 1389736
TI  - Continuous wave Doppler echocardiography after surgical repair of coarctation of
      the aorta.
AB  - OBJECTIVE: To find how closely pressure gradients across the aortic arch derived
      from Doppler echocardiography reflect gradients measured by catheter after
      surgical repair of coarctation of the aorta. DESIGN: Pressure drop across the
      aortic arch was measured simultaneously by continuous wave Doppler and double
      lumen catheter in 20 patients with repaired coarctation of the aorta. RESULTS:
      The peak pressure drop estimated by Doppler was almost invariably higher than the
      peak to peak gradient measured by catheter, as might be expected. Wide variation
      was seen between the Doppler measured pressure drop and instantaneous peak
      gradient measured by catheter, ranging from +22 to -17 mm Hg. The reasons for
      these differences are unclear but are probably related to a combination of
      complex flow dynamics in the aortic arch, difficulty in closely aligning the
      Doppler beam with flow, and inability to measure flow velocity immediately
      proximal to the site of the surgical repair with continuous wave Doppler.
      CONCLUSIONS: Continuous wave Doppler echocardiography may significantly
      overestimate or underestimate the pressure drop after repair of coarctation and
      it should be interpreted with caution in individual patients. Catheterisation
      with angiography remains the reference standard for assessment of surgical repair
      of the aortic arch.

PMID- 1389737
TI  - Optimal pacing modes after cardiac transplantation: is synchronisation of
      recipient and donor atria beneficial?
AB  - OBJECTIVE: To investigate the response of the transplanted heart to different
      pacing modes and to synchronisation of the recipient and donor atria in terms of
      cardiac output at rest. DESIGN: Doppler derived cardiac output measurements at
      three pacing rates (90/min, 110/min and 130/min) in five pacing modes: right
      ventricular pacing, donor atrial pacing, recipient-donor synchronous pacing,
      donor atrial-ventricular sequential pacing, and synchronous recipient-donor
      atrial-ventricular sequential pacing. PATIENTS: 11 healthy cardiac transplant
      recipients with three pairs of epicardial leads inserted at transplantation.
      RESULTS: Donor atrial pacing (+11% overall) and donor atrial-ventricular
      sequential pacing (+8% overall) were significantly better than right ventricular
      pacing (p < 0.001) at all pacing rates. Synchronised pacing of recipient and
      donor atrial segments did not confer additional benefit in either atrial or
      atrial-ventricular sequential modes of pacing in terms of cardiac output at rest
      at these fixed rates. CONCLUSIONS: Atrial pacing or atrial-ventricular sequential
      pacing appear to be appropriate modes in cardiac transplant recipients.
      Synchronisation of recipient and donor atrial segments in this study produced no
      additional benefit. Chronotropic competence in these patients may, however,
      result in improved exercise capacity and deserves further investigation.

PMID- 1389738
TI  - Arrhythmias after the Fontan procedure.
AB  - OBJECTIVE: To study the determinants and outcome of arrhythmias after the Fontan
      type operation. DESIGN: Retrospective analysis of data in patients operated on
      between 1972 and 1986 (follow up 5-19 years (mean 12 years)). PATIENTS: All 60
      patients undergoing a Fontan type procedure at the National Heart Hospital,
      London, during the study period (mean age (SD) 12.3 (6.8) years). RESULTS:
      Postoperative arrhythmias occurred in 34 patients (57%), and 11 (58%) of 19 early
      postoperative deaths (within seven days) were related to arrhythmias. Early
      arrhythmias occurred in 19 (32%) patients of whom 11 (58%) died. All patients
      with early atrial fibrillation and His bundle tachycardia died and only
      preoperative atrial fibrillation recurred early. There was a higher incidence of
      early arrhythmias, which were less well tolerated, in double inlet single
      ventricle patients (9/19) than in those with tricuspid atresia (8/37). There were
      no other preoperative determinants of early arrhythmias or deaths from early
      arrhythmia. Late (after seven days) arrhythmias occurred in 15 (37% of hospital
      survivors). They had higher right atrial (RA) pressures both early and late after
      operation and had lower ventricular ejection fractions late after operation. Of
      those with atrial arrhythmias 86% had RA obstruction and 57% had an RA thrombus
      or pulmonary embolism at presentation; this was also confirmed in two patients in
      whom late sudden deaths occurred. Atrial fibrillation early after reoperation for
      RA obstruction was fatal. The actuarial arrhythmia free survival for hospital
      survivors was 60% at 10 years. CONCLUSIONS: Early postoperative arrhythmias were
      poorly tolerated, particularly atrial fibrillation and His bundle tachycardia.
      Previous atrial fibrillation was a relative contraindication to this procedure.
      Late postoperative arrhythmias were associated with higher RA pressures measured
      both early and late after operation and worse late ventricular function. Late
      arrhythmias may be the first manifestation of RA obstruction, which must be
      sought. RA thrombus was common in patients with atrial arrhythmias and should be
      treated early with anticoagulants.

PMID- 1389740
TI  - Raised international normalised ratio (INR): is it a cause or an effect of late
      cardiac tamponade?
AB  - Two cases of late cardiac tamponade after valve replacement surgery are reported:
      both patients were treated with oral anticoagulants (warfarin) after operation.
      An erratic response in the international normalised ratio (INR) was found before
      the diagnosis of late tamponade. It is suggested that this response of the INR
      may be an early indicator of late cardiac tamponade rather than a cause.

PMID- 1389739
TI  - Repeatability of measurements and sources of variability in tests of
      cardiovascular autonomic function.
AB  - OBJECTIVE: To determine the repeatability and sources of variability of clinical
      tests of cardiovascular autonomic function. DESIGN: The commonly used
      electrocardiographic related tests of autonomic function were studied. Two repeat
      measurements of all tests were made on all subjects on four separate days over a
      four week period. SUBJECTS: Ten normal subjects with no known autonomic
      dysfunction were investigated. MAIN OUTCOME MEASURES: These were deep breathing
      (subject seated and supine), Valsalva manoeuvre, standing up from lying position,
      and normal relaxed breathing (subject supine). During the tests the
      electrocardiogram and respiratory pattern were recorded by computer. Beat to beat
      RR intervals were measured automatically from the electrocardiogram, and from
      these the results of the tests were calculated. RESULTS: Variance analysis showed
      significant between subject variability for all tests (p < 0.005), but some tests
      showed a much smaller relative within subject variability than others. Average
      repeatability data (within subject SD) for each test were calculated, and
      included deep breathing sitting (max-min) RR (46 ms), Valsalva ratio (0.17), and
      lying to standing RR ratio (0.11). These compare with between subject SDs of 65
      ms, 0.38, and 0.13 respectively, at mean values of 305 ms, 1.92, and 1.15
      respectively. The data highlighted one subject with the poorest repeatability,
      whose electrocardiogram turned out on closer inspection to be under atrial rather
      than sinus control at times. Poor repeatability in the other subjects was related
      to variability in the respiratory pattern, and in the deep breathing test, repeat
      variability was significantly correlated (r = 0.79) with variability in the
      respiratory amplitude (p < 0.05). CONCLUSIONS: Repeatability data should be
      available to each laboratory carrying out autonomic function tests. The data
      provided in this study could be used as a baseline. Poor repeatability highlights
      the need to re-examine the test procedures, or the test data from specific
      subjects. Variability of respiratory pattern is associated with poor
      repeatability, and so careful instructions on respiration should be given to each
      subject before the tests.

PMID- 1389741
TI  - Rare variant of truncus arteriosus with intact ventricular septum and hypoplastic
      right ventricle.
AB  - A three week old girl was admitted to hospital with severe congestive heart
      failure and cyanosis. Cross sectional and Doppler echocardiography and cardiac
      catheterisation showed a unique variant of truncus arteriosus with an intact
      ventricular septum. The trunk rose only from the left ventricle and was
      associated with a hypoplastic right ventricle with sinusoids to the right
      coronary artery.

PMID- 1389742
TI  - Unmasking of a second atrioventricular accessory connection by adenosine in a
      child with a long RP' reentrant tachycardia.
AB  - A second unidirectional, retrograde accessory atrioventricular pathway was
      unmasked by adenosine during the intracardiac evaluation of a child with a
      reentrant long RP' tachycardia. This case is further evidence of the value of
      adenosine during the evaluation of these types of tachycardias.

PMID- 1389743
TI  - Propionibacterium acnes causing an aortic root abscess.
AB  - A case of endocarditis caused by Propionibacterium acnes associated with an
      aortic root abscess is presented. This supports the current opinion that aortic
      root abscesses are not necessarily associated with microorganisms of high
      virulence.

PMID- 1389744
TI  - Dilated cardiomyopathy associated with chronic overuse of an adrenaline inhaler.
AB  - Endogenous catecholamines in excess are known to cause dilated cardiomyopathy. A
      patient presented with dilated cardiomyopathy after many years of overusing an
      adrenaline inhaler. Pathological features and a considerable improvement in
      myocardial function after withdrawal implicated the exogenous catecholamine
      excess in the pathogenesis of the cardiomyopathy.

PMID- 1389745
TI  - Validation of the beat to beat measurement of blood velocity in the human
      ascending aorta by a new high temporal resolution Doppler ultrasound spectral
      analyser.
AB  - OBJECTIVE: To develop and validate a high temporal resolution spectral analysis
      system for Doppler measurements of blood velocity in the ascending aorta. DESIGN:
      An observational laboratory and clinical study comparing Doppler velocity-based
      measurements with fluid collection, electromagnetic flow catheters and probes,
      and thermodilution. SETTING: Tertiary referral cardiology unit and cardiac
      catheter laboratory. PATIENTS: Patients undergoing routine cardiac
      catheterisation for ischaemic heart disease, cardiac failure, and primary
      pulmonary hypertension. RESULTS: There was good agreement between Doppler-derived
      and electromagnetic cuff or catheter measurements of velocity in an experimental
      flow rig (SD of differences 4.75% for velocity integral) and in the patients (SD
      of differences 4% for velocity integral). There was also reasonably good
      agreement between simultaneous Doppler-derived and thermodilution-estimated
      cardiac output measurements in patients undergoing cardiac catheterisation (SD of
      differences 12.6%). CONCLUSIONS: This new method of high temporal resolution
      spectral analysis improves the resolution of rapidly changing blood velocities
      and may improve the ability to describe blood velocity patterns in the ascending
      aorta.

PMID- 1389746
TI  - A new system for ambulatory pulmonary artery pressure recording.
AB  - OBJECTIVE: To develop a complete system for the measurement, recording, and
      analysis of ambulatory pulmonary artery pressure. DESIGN: The new system consists
      of a pulmonary artery catheter, an ambulatory recorder, and a desktop computer.
      Pulmonary artery pressure is measured by a micromanometer tipped catheter with an
      in vivo calibration system to allow correction for zero drift. This catheter is
      plugged into a small battery powered recorder. The recorder has two input
      channels, one for pressure and one for an event marker. The pressure wave is
      sampled 32 times/s, processed by an in built computer, compressed, and stored in
      semi-conductor memory. On completion of a recording, data is transferred from the
      ambulatory recorder through a serial data link to an Acorn Archimedes desktop
      computer on which further data processing, statistical analysis, graphics, and
      printouts can be obtained. RESULTS: The system has been used in 18 patients, with
      technically successful recording in 14, less than 15 minutes of data loss in
      three, and 12 hours of data loss in one. CONCLUSIONS: A new system for ambulatory
      pulmonary artery monitoring has been developed and used clinically with success.
      It may provide new perspectives on the pathophysiology of disease as it applies
      to everyday life.

PMID- 1389747
TI  - Calculation of aortic regurgitation orifice area by Doppler echocardiography: an
      application of the continuity equation.
AB  - The evaluation of aortic regurgitation by current echocardiographic techniques
      has been qualitative and load-dependent. The area of the regurgitant orifice,
      which is theoretically independent of haemodynamic conditions, has not been
      determined non-invasively. In 20 patients with various degrees of aortic
      regurgitation, this area was determined by use of the continuity equation applied
      during diastole. The velocity-time integrals were determined at the supravalvar
      (VTIs) and regurgitant orifice (VTIj) levels by pulsed and continuous wave
      Doppler respectively. The cross sectional area at the supravalvar level (As) was
      also measured by cross sectional echocardiography. The regurgitant orifice is
      given by: (As x VTIs)/VTIj. Other non-invasive measurements of the aortic
      regurgitation severity were also recorded: (a) an overall echo score (1-5+) given
      blindly by two echocardiographers, (b) the maximal proximal jet width by colour
      Doppler, (c) left ventricular end systolic and end diastolic volumes and left
      ventricular mass. The regurgitant area ranged from 0.25 to 1.7 cm2 and this area
      accorded with the overall echo score and the maximal proximal jet width measured
      by colour Doppler. The aortic regurgitation orifice area can be calculated non
      invasively and it may be a quantitative measure of the severity of aortic
      regurgitation.

PMID- 1389748
TI  - Cost effectiveness of the implantable cardioverter defibrillator: a preliminary
      analysis.
AB  - BACKGROUND: An implantable cardioverter defibrillator (ICD) may be effective in
      reducing the risk of sudden cardiac death. The high cost of ICD treatment,
      however, compared with alternatives raises the question of whether this new
      technology is an efficient use of scarce health care resources. OBJECTIVE: To
      estimate the incremental cost effectiveness of the implantable cardioverter
      defibrillator compared with drug treatment with amiodarone in the management of
      patients at high risk of sudden cardiac death. DESIGN: A cost effectiveness model
      was constructed from data already published and other secondary sources.
      Differences in patient survival were calculated from life tables for comparable
      ICD and amiodarone patient series. Costs were based on typical patient management
      protocols derived from current United Kingdom practice and interviews with
      physicians. MAIN OUTCOME MEASURES: Cost effectiveness of ICD treatment was
      computed over 20 years; all future costs and effects were discounted at 6% per
      year. RESULTS: Estimated life expectancy was 11.1 and 6.7 years with ICD and
      amiodarone respectively; the discounted 20 year difference lies in the range 1.7
      to 3.7 years. Discounted 20 year treatment costs were 28,400 pounds for the ICD
      and 2300 pounds for amiodarone. Cost effectiveness of ICD treatment lies in the
      range of 15,400 pounds to 8200 pounds per life-year gained. CONCLUSIONS: Cost
      effectiveness of ICD treatment is similar to some existing cardiac programmes
      funded under the NHS but uncertainty exists due to limitations of the data. Costs
      of ICD treatment may fall in the future as the life of the device increases and
      less invasive implantation methods are needed. The effectivess of ICD compared
      with amiodarone is currently being studied by a randomised controlled trial.

PMID- 1389749
TI  - Walter Hayle Walshe (1812-1892) and his book Diseases of the Heart.

PMID- 1389750
TI  - Management of patients with Bjork-Shiley prosthetic valves.

PMID- 1389751
TI  - Abnormal right heart filling after cardiac surgery.

PMID- 1389753
TI  - Coronary artery disease after heart transplantation: clinical aspects.

PMID- 1389752
TI  - Graft vascular disease in heart transplant patients.

PMID- 1389754
TI  - Ventricular remodelling after myocardial infarction.

PMID- 1389755
TI  - Coronary occlusive disease and late graft failure after cardiac transplantation.
AB  - OBJECTIVE: Coronary occlusive disease is the main cause of late mortality after
      cardiac transplantation. It has both similarities and differences compared with
      conventional atherosclerotic coronary disease. The pathophysiology of late graft
      failure from coronary occlusive disease is unclear at present. We reviewed the
      experience of this disorder in our cardiac transplant programme. DESIGN: A
      retrospective analysis of angiographic and pathological data. SETTING: A regional
      cardiothoracic centre and transplant unit. PATIENTS: Of a population of 383
      orthotopic cardiac transplant recipients operated upon between January 1979 and
      June 1990, 447 coronary angiograms were available for review in 193 patients.
      Thirteen of a possible 18 results of post mortem examinations from patients dying
      from coronary occlusive disease were available. MAIN OUTCOME MEASURE: Coronary
      occlusive disease was defined as any evidence of disease on coronary angiography.
      Post mortem examinations were performed with standard techniques. RESULTS: The
      angiographic prevalence of coronary occlusive disease was 3% (1/32 patients) and
      40% (19/47 patients) at one and five years respectively. Twenty six grafts failed
      due to coronary occlusive disease compared with 132 graft failures from all
      causes during this period. Acute thrombosis was present in a large vessel in
      seven of 13 fatal cases undergoing necropsy (54%). Noticeable large vessel
      involvement with disease in smaller distal vessels was present in four patients
      (31%). The remaining two patients (15%) had small vessel disease alone. Twelve of
      the 13 patients had significant cardiomegaly (cardiac weight > or = 400 g) with a
      mean weight of 510 (range 370-740) g. CONCLUSION: Coronary occlusive disease is
      the main late complication after cardiac transplantation. A combination of
      coronary thrombosis, ischaemia from stenoses of large and small coronary vessels,
      and cardiomegaly contribute to the graft failure of these patients.

PMID- 1389756
TI  - Impairment of coronary flow reserve in orthotopic cardiac transplant recipients
      with minor coronary occlusive disease.
AB  - OBJECTIVE: Coronary occlusive disease is the major long-term complication after
      cardiac transplantation. The relation between minor angiographic abnormalities
      and myocardial perfusion has not been previously assessed in a large number of
      cardiac transplant patients. DESIGN: Prospective study. Coronary flow reserve was
      measured with an intracoronary Doppler flow probe in the proximal left anterior
      descending coronary artery in each patient. A dose of intracoronary papaverine
      producing maximal vasodilation was then administered. SETTING: A regional
      cardiothoracic centre and a supraregional transplant unit. PATIENTS: Seven
      patients with chest pain but normal coronary anatomy (controls), and 61 cardiac
      transplant patients between three months and 10 years after operation (median 4.5
      years). Twenty one cardiac transplant patients had angiographic evidence of minor
      coronary occlusive disease (mean (SD) percentage stenosis diameter 23% (6%)) in a
      primary or secondary coronary vessel (group 1), with 12 of these in the left
      anterior descending coronary artery (stenosis diameter (mean (SD) 24% (8%)). The
      remaining 40 transplant patients had normal coronary angiograms (group 2). MAIN
      OUTCOME MEASURE: Coronary flow reserve was defined as the ratio of the peak flow
      velocity after papaverine to the resting flow velocity. RESULTS: Group 1 patients
      had a noticeably impaired coronary flow reserve (2.6 (1.1)) compared with control
      patients (3.9 (0.4), p = 0.05) and, after adjusting for year after operation,
      compared with group 2 patients (3.8 (1.0), p < 0.001). No other variables were
      associated with a reduction in coronary flow reserve. Mean resting flow velocity
      was similar in all three groups (controls, 7.4 (4.6) cm/s; group 1, 7.5 (5.9)
      cm/s; and group 2, 7.3 (3.9) cm/s). Mean peak flow velocity response to
      papaverine was reduced in group 1 patients (18.1 (13.5) cm/s) relative to group 2
      patients (27.5 (15.4) cm/s, p = 0.05) but not controls (28.4 (15.1) cm/s, p =
      0.1). CONCLUSIONS: Coronary flow reserve and the peak flow response to the
      coronary vascular smooth muscle relaxant papaverine are impaired in cardiac
      transplant patients with minor coronary occlusive disease. This disturbance of
      cardiac microvascular function may contribute to the late morbidity and mortality
      seen in cardiac transplant patients with coronary occlusive disease.

PMID- 1389757
TI  - Nuclear magnetic resonance spectroscopy of excised human hearts.
AB  - BACKGROUND: Phosphorus nuclear magnetic resonance spectroscopy has been proposed
      as a method of studying the metabolism of the myocardium in patients. Little is
      known about 31P nuclear magnetic resonance spectroscopy of diseased human hearts.
      METHODS: Two donor hearts meeting the requirements for heart transplantation and
      11 diseased hearts were removed during a transplantation procedure and were
      studied in a horizontal 2.35 T superconducting magnet. Spectra were obtained at 0
      degrees C about 30 minutes after the excision. The areas of the inorganic
      phosphate peak (Pi) and of the phosphocreatine peak (PCr) were summed and
      expressed as a ratio with respect to the area of the beta ATP peak. RESULTS: The
      ratio (Pi + PCr)/beta ATP was found to be significantly lower in five hearts with
      a myocardial infarct (0.77 (0.18)) than in hearts with dilated cardiomyopathy
      (1.25 (0.29)) and in normal hearts (1.69 (0.11)). The area of the phosphodiester
      peak was expressed as a ratio with respect to the area of the beta ATP peak: no
      differences were found between the three groups. CONCLUSIONS: These results
      suggest that the phosphocreatine concentration is lower in ischaemic heart
      disease than in dilated cardiomyopathy and that the phosphodiester peak is
      probably not useful in distinguishing between these two types of heart disease.

PMID- 1389758
TI  - Intravascular ultrasound imaging of the coronary arteries: an in vitro evaluation
      of measurement of area of the lumen and atheroma characterisation.
AB  - OBJECTIVE: To assess the accuracy of measurement of area of the lumen, and
      sensitivity, and specificity of detection of atheroma in coronary arteries in
      vitro with a commercially available 20 MHz intravascular ultrasound system.
      SETTING: A teaching hospital department of cardiology with the support of the
      department of cardiovascular pathology. PROCEDURE: 10 segments of coronary artery
      were removed from cadaver hearts. Intravascular ultrasound imaging was performed
      at fixed levels and the vessels were then sectioned and photographed before
      histological preparation. An independent blinded observer measured luminal area
      and assessed the presence of atheroma on the intravascular ultrasound images of
      76 vessel sections (304 quadrants). The sensitivity and specificity of detection
      of atheroma was assessed in comparison with the histologically prepared sections.
      Luminal areas from intravascular ultrasound, photographs of cross sections of the
      vessels and histological sections were compared with the technique of limits of
      agreement. RESULTS: Overall 36% of the 304 quadrants studied histologically had
      identifiable atheroma. Intravascular ultrasound sensitivity for atheroma was
      0.593 and the specificity was 0.839. The positive predictive value was 0.674, and
      the relative risk 3.139. Values for area of the vessel lumen were on average 9.4
      mm2 (confidence interval (CI) 8.6-10.2 mm2) larger than those measured from
      photographs and 10.7 (CI 9.8-11.6 mm2) larger than those measured from the
      histological sections. CONCLUSIONS: The intravascular ultrasound system assessed
      in this study significantly overestimated coronary vessel luminal area and had
      low sensitivity and specificity for detection of atheroma. Improvements in image
      resolution are required before this system can provide useful information on
      coronary artery size and morphology.

PMID- 1389759
TI  - Lower threshold for adenosine-induced chest pain in patients with angina and
      normal coronary angiograms.
AB  - OBJECTIVE: To investigate whether patients with angina-like chest pain and normal
      coronary angiograms are more sensitive to adenosine as an inducer of chest pain.
      DESIGN: Increasing doses of adenosine were given in a single blind study as
      intravenous bolus injections. Chest pain and the electrocardiographic findings
      were noted. PATIENTS: Eight patients with angina-like chest pain but no coronary
      stenoses (group A), nine patients with angina and coronary stenoses (group B),
      and 16 healthy volunteers (group C). RESULTS: In the absence of ischaemic signs
      on the electrocardiogram adenosine provoked angina-like pain in all patients in
      groups A and B. The pain was located in the chest, and its quality and location
      were described as being no different from the patient's habitual angina. In group
      C, 14 of 16 subjects reported chest pain. The lowest dose resulting in chest pain
      was lower in group A (0.9 (0.6) mg) than in group B (3.1 (1.5)mg) (p < 0.005) and
      in group C (6.2 (3.7) mg) (p < 0.005). The maximum tolerable dose was lower in
      group A (4.7 (2.1) mg) than in group B (9.2 (3.8) mg) (p < 0.05) and in group C
      (12.0 (4.1) mg) (p < 0.005). CONCLUSIONS: Patients with angina-like chest pain
      and normal coronary angiograms have a low pain threshold and low tolerance to
      pain induced by adenosine.

PMID- 1389760
TI  - Detection of myocardial ischaemia by transthoracic leads in ambulatory
      electrocardiographic monitoring.
AB  - OBJECTIVE: To determine the best sites for ambulatory monitoring leads to detect
      myocardial ischaemia. PATIENTS: 50 consecutive patients recovering from
      myocardial infarction. Six patients were excluded because of unsatisfactory
      recordings or baseline electrocardiographic abnormalities that influenced the
      diagnostic accuracy of ST segment depression. In 38 patients important ST segment
      changes were seen before the study recordings. MAIN OUTCOME MEASURE:
      Reproducibility of detecting the electrocardiographic ST segment changes with 12
      bipolar leads alone or in combination. RESULTS: The highest reproducibility rate
      was found in infarcts involving both the anterior and inferior left ventricular
      walls (80%). The reproducibility decreased as the extent of ventricular wall
      involvement decreased and was lowest in inferior infarcts (31%) (p < 0.001). For
      large infarcts the detection rate was almost equal for the 12 study leads,
      whereas disparity between leads increased as the infarct size decreased. The
      highest overall reproducibility was found in a transthoracic lead (V2, V9R)
      (76%). This lead was significantly better (p = 0.03) than lead CM5 (50%). When
      the transthoracic lead was combined with an inferior lead, the reproducibility
      increased (82%) and was significantly better than the combination of CM5 and an
      inferior lead (58%) (p = 0.02). CONCLUSIONS: Extensive ischaemic
      electrocardiographic changes are better detected than smaller ones and anterior
      infarcts better than inferior. A transthoracic lead (V2, V9R) was significantly
      better than CM5 both alone and when CM5 and the transthoracic lead were combined
      with an inferior lead.

PMID- 1389761
TI  - Optimal control of myocardial ischaemia: the benefit of a fixed combination of
      atenolol and nifedipine in patients with chronic stable angina.
AB  - OBJECTIVE: To study the effects on myocardial ischaemia of 50 mg of atenolol, 20
      mg of slow release nifedipine, and their fixed combination given 12 hourly.
      DESIGN: A treadmill exercise test and 24 hour ambulatory electrocardiographic
      monitoring were carried out after a period of five days off treatment (control)
      and at the end of three weeks of each treatment period. PATIENTS: 23 patients
      with stable angina pectoris, documented coronary artery disease, and a positive
      exercise test were randomised in a double blind, three way, cross over study.
      RESULTS: Compared with the control, nifedipine significantly induced an increase
      in resting heart rate of (mean (SEM)) 14 (2) beats/min whereas atenolol and the
      combination significantly reduced it by 24 (2) and 20 (1) beats/min respectively.
      The number of exercise tests rendered negative after each intervention was five
      for nifedipine, nine for atenolol, and 11 for the combination. Compared with the
      control the time to the start of myocardial ischaemia (1 mm ST segment
      depression) during exercise significantly increased by 3.2 (0.6) min after
      nifedipine, by 4.6 (0.4) min after atenolol, and by 4.6 (0.5) min after the
      combination; rate-pressure product (beats/min. mm Hg) at 1 mm ST segment
      depression increased by 2824 (970) after nifedipine but fell by 4436 (900) and
      4501 (719) after atenolol and the combination. The weekly frequency of angina was
      reduced from a mean of five while taking nifedipine, to three while taking
      atenolol, and to two while taking the combination. The total ischaemic time
      during ambulatory monitoring was significantly reduced from 69 (17) min during
      control to 37.5 (9.8) min during nifedipine, to 15.6 (5.5) min during atenolol,
      and to 6.5 (2.7) min during the combination. CONCLUSION: The undesirable effect
      of a high basal heart rate induced by nifedipine was neutralised by its
      combination with atenolol. Whereas atenolol and the combination were equally
      efficacious in controlling exercise induced ischaemia, the combination was more
      effective in reducing total ischaemic burden.

PMID- 1389762
TI  - Usefulness of Doppler echocardiographic assessment of diastolic filling in
      distinguishing "athlete's heart" from hypertrophic cardiomyopathy.
AB  - OBJECTIVE: In some athletes with a substantial increase in left ventricular wall
      thickness, it may be difficult to distinguish with certainty physiological
      hypertrophy due to athletic training from hypertrophic cardiomyopathy. The
      purpose of the present investigation was to determine whether assessment of left
      ventricular filling could differentiate between these two conditions. DESIGN:
      Doppler echocardiography was used to obtain transmitral flow velocity waveforms
      from which indices of left ventricular diastolic filling were measured. Normal
      values were from 35 previously studied control subjects. SETTING: Athletes were
      selected mostly from the Institute of Sports Science (Rome, Italy), and patients
      with hypertrophic cardiomyopathy were studied at the National Institutes of
      Health (Bethesda, Maryland). PARTICIPANTS: The athlete group comprised 16 young
      competitive athletes with an increase in left ventricular wall thickness (range
      13-16 mm; mean 14). For comparison, 12 symptom free patients with non-obstructive
      hypertrophic cardiomyopathy were selected because their ages and degree of
      hypertrophy were similar to those of the athletes. RESULTS: In the athlete group,
      values for deceleration of flow velocity in early diastole, peak early and late
      diastolic flow velocities, and their ratio were not significantly different from
      those obtained in untrained normal subjects; furthermore, Doppler diastolic
      indices were normal in each of the 16 athletes. Conversely, in patients with
      hypertrophic cardiomyopathy, mean values for Doppler diastolic indices were
      significantly different from both normal subjects and athletics (p = 0.01 to
      0.003), and one or more indices were abnormal in 10 (83%) of the 12 patients.
      CONCLUSIONS: Doppler echocardiographic indices of left ventricular filling may
      aid in distinguishing between pronounced physiological hypertrophy due to
      athletic training and pathological hypertrophy associated with hypertrophic
      cardiomyopathy.

PMID- 1389763
TI  - Protrusion of the device: a complication of catheter closure of patent ductus
      arteriosus.
AB  - OBJECTIVE: To assess the medium term results of percutaneous transvenous closure
      of patent ductus arteriosus, in particular with regard to protrusion of the
      device with or without turbulence of the bloodflow. DESIGN: Clinical examination
      and echocardiographic study (cross sectional Doppler, and colour Doppler
      examination) within 24 hours of and at least 6 months after implantation (range 6
      26 (mean 15) months). SETTING: Multicentre study at the departments of paediatric
      cardiology of three academic hospitals. Tertiary clinical care of the first group
      of patients in the Netherlands treated by the percutaneous transvenous method.
      PATIENTS: 36 patients (12 male, 24 female) mean age 8.2 years, (range 1.7-58.3),
      mean weight 25.5 kg (range 11-67.8 kg). The total group consisted of 46 patients.
      In one the implantation had failed and nine others were not available for regular
      follow up. All 36 patients underwent non-surgical closure of the patent ductus
      arteriosus with a Rashkind double umbrella prosthesis. MAIN OUTCOME MEASURES:
      Diagnosis or exclusion of protrusion of the Rashkind device with or without
      turbulence of the blood flow with follow up of changes in protrusion and
      turbulence. RESULTS: In 17 patients the prosthesis protruded into an arterial
      lumen: the aorta in 13 and the (left) pulmonary artery in four, with turbulence
      in seven and two cases respectively. After six months the aortic protrusion
      disappeared in three, including one who had had turbulent blood flow. At the end
      of follow up the prosthesis still protruded into the aorta in 10 but in three the
      turbulence had vanished. In two of the three remaining patients with turbulence
      in the descending aorta the degree of turbulence had decreased. There was no
      lessening of turbulence in the four patients in whom the device protruded into
      the pulmonary artery. CONCLUSIONS: The Rashkind double umbrella can protrude into
      the descending aorta and the left pulmonary artery without causing turbulent
      blood flow. Turbulence and the protrusion itself can disappear. Endocarditis
      prophylaxis may be required for as long as the device causes turbulence.

PMID- 1389764
TI  - Subclinical cardiomyopathy in Becker muscular dystrophy.
AB  - OBJECTIVE: To investigate the prevalence, age distribution, and spectrum of
      cardiac involvement in a cohort of patients with Becker muscular dystrophy.
      DESIGN: A prospective non-invasive study with clinical, electrocardiographic, and
      echocardiographic assessment. PATIENTS: 19 patients (age range 16-41 years) with
      Becker muscular dystrophy attending the Muscle Clinic at Hammersmith Hospital and
      22 healthy controls (age range 22-36 years). RESULTS: 17 patients (89%) were
      symptom free; two had exertional dyspnoea. Three had a past history of acute
      pericarditis. The electrocardiogram was abnormal in 14 patients (74%).
      Intraventricular conduction delay or right bundle branch block was present in
      eight (42%). Three (16%) had tall R waves (R/S > 1) in lead V1 in the absence of
      right bundle branch block and eight (42%) had Q waves in the lateral and
      inferolateral leads. The PQ interval was significantly shorter in patients with
      Becker muscular dystrophy (p < 0.01). Echocardiography showed left ventricular
      dilatation in seven patients (37%) and 12 (63%) had subnormal systolic function
      caused by global hypokinesia (fractional shortening < 27%). Six of these patients
      were under the age of 22 years. Patients with Becker muscular dystrophy had
      significant reduction of both fractional shortening and corrected mean velocity
      of circumferential shortening compared with controls. No correlation was found
      between fractional shortening and age. The third filling fraction was
      significantly reduced in patients with Becker muscular dystrophy (p < 0.05),
      although other indices of diastolic function (isovolumic relaxation time and E/A
      ratios) were not significantly different. CONCLUSIONS: Though most patients with
      Becker muscular dystrophy were symptom free, a high percentage had evidence of a
      subclinical cardiomyopathy. Electrocardiography showed that the inferolateral and
      posterior segments of the left ventricle tended to be affected and may show
      evidence for conduction tissue disease. Echocardiography showed that most
      patients had left ventricular dilation and global hypokinesia. The severity of
      left ventricular disease was unrelated to age; some younger patients had severe
      left ventricular dysfunction. All patients with Becker muscular dystrophy should
      have echocardiographic assessment of left ventricular function.

PMID- 1389765
TI  - Magnetic resonance imaging of hearts with atrioventricular valve atresia or
      double inlet ventricle.
AB  - OBJECTIVE: To investigate the effectiveness and limitations of magnetic resonance
      imaging in defining cardiac anatomy in patients with double inlet ventricle or
      atrioventricular valve atresia. DESIGN: Magnetic resonance images were reviewed
      retrospectively without reference to other morphological data. SETTING: A
      tertiary referral centre for paediatric cardiology. PATIENTS: 18 patients (aged 8
      days to 27 years) with a suspected univentricular atrioventricular connection.
      METHODS: Imaging by a 1.5 T whole body magnetic resonance system with imaging
      planes adjusted to individual patient anatomy to best define the cardiac
      morphology. A complete sequential diagnosis obtained from an independent
      interpretation of the images was compared with the diagnosis obtained from cross
      sectional echocardiography and angiocardiography. RESULTS: There was substantial
      accord between the diagnosis from magnetic resonance alone and that from other
      methods. In the six instances where there was not accord the magnetic resonance
      diagnosis was considered to be correct in two cases and incorrect in three cases.
      In the remaining case no consensus could be reached. In eight patients magnetic
      resonance imaging provided anatomical information additional to that from other
      methods. The strengths of magnetic resonance were in imaging the pulmonary
      arteries and their abnormalities and identifying juxtaposed atrial appendanges
      but there were some deficiencies in identifying Blalock-Taussig shunts.
      CONCLUSION: Magnetic resonance imaging provided detailed information about all
      aspects of cardiac morphology in patients with a suspected diagnosis of
      univentricular atrioventricular connection. Often it provided additional
      information to echocardiography. Its use in selected patients should give
      valuable complementary information.

PMID- 1389766
TI  - Successful repair of pulmonary atresia with ventricular septal defect without the
      use of a conduit: a new surgical option. Report of two cases.
AB  - A new technique for the restoration of continuity between the pulmonary artery
      and the right ventricle in pulmonary atresia with ventricular septal defect
      without the use of a conduit is described. This was accomplished by anastomosing
      the inferior margin of the distal pulmonary artery to the apex of a T-shaped
      infundibular ventriculotomy to form the posterior wall of the reconstructed right
      ventricular outflow tract. A winged patch of bovine pericardium was then used for
      the anterior wall to complete reconstruction of the transannular right
      ventricular outflow tract. This technique was used successfully in two patients.

PMID- 1389767
TI  - Fabry's disease with complete atrioventricular block: histological evidence of
      involvement of the conduction system.
AB  - A 63 year old man with complete atrioventricular block was diagnosed as having
      Fabry's disease. A short PR interval is a common electrocardiographic finding in
      Fabry's disease, but complete atrioventricular block is a very rare complication.
      Necropsy indicated that lipid accumulation in the atrioventricular conduction
      system was the probable cause of this patient's atrioventricular block.

PMID- 1389768
TI  - Right-sided endomyocardial fibrosis with recurrent pulmonary emboli leading to
      irreversible pulmonary hypertension.
AB  - A 26 year old Saudi man with features of both Loeffer's endocarditis and
      endomyocardial fibrosis presented with mild symptoms and pulmonary emboli.
      Echocardiographic examination showed obliteration of the right ventricular apex
      by an attached mass. The results of haemodynamic studies were somewhat abnormal
      and medical treatment was started. Despite anticoagulation with warfarin the
      patient's condition deteriorated rapidly over a four month period after a further
      episode of pulmonary embolism and the development of pulmonary hypertension. Two
      haemodynamic studies performed four months apart were typical of pulmonary
      hypertension and later right ventricular failure; they showed none of the
      characteristics of restriction. Pulmonary embolectomy was attempted but there was
      no cleavage plane between the organised thrombi and the endothelium of the
      pulmonary artery. The patient died of severe pulmonary hypertension and right
      ventricular failure several days after operation. Surgical intervention in the
      early stages of right-sided endomyocardial fibrosis might have prevented the
      development of pulmonary embolism and pulmonary hypertension.

PMID- 1389769
TI  - Anomalous origin of the right coronary artery from the pulmonary artery in
      association with congenital aneurysm of the sinus of Valsalva: angiographic
      diagnosis of a rare association.
AB  - A 37 year old man presenting with acute heart failure, hypotension, and acute
      renal failure was diagnosed by cardiac catheterisation and angiography to have
      the rare combination of congenital aneurysm of the non-coronary sinus of Valsalva
      rupturing into the right ventricle, and an anomalous origin of the right coronary
      artery from the main pulmonary artery. The diagnosis could not be confirmed by
      transthoracic echocardiography in this patient. This combination of defects,
      confirmed at cardiac surgery, has not been reported before, and this case report
      highlights the importance of preoperative definition of congenital defects
      associated with an aneurysm of the sinus of Valsalva.

PMID- 1389770
TI  - Cardiac assistance from skeletal muscle: a critical appraisal of the various
      approaches.
AB  - We review here various ways in which cardiac assistance might be derived from a
      patient's own skeletal muscle. Calculations based on experimental data and
      optimistic estimates of the efficiency of the energy conversions involved suggest
      that the continuous assist available would be limited to about 2 litres a minute
      if a muscle were used to energise an electromechanical device. It would be more
      efficient to couple the energy mechanically or hydraulically, but these
      approaches still pose problems of anatomical placement, muscle attachment, fluid
      leakage, and cost. Unless these issues can be addressed, the use of skeletal
      muscle as an internal power source for mechanical circulatory assist devices will
      remain an unworkable concept. Configurations that couple skeletal muscle
      contraction directly to the circulation would be more efficient and less costly.
      In terms of the energy available, a skeletal muscle ventricle could be designed
      to provide a continuous partial assist of 1-2 l/min, with flows of up to 8 l/min
      sustainable for limited periods. Such an approach offers new possibilities for
      the surgical treatment of chronic cardiac failure.

PMID- 1389771
TI  - Surgical cover for percutaneous transluminal coronary angioplasty. The Council of
      the British Cardiovascular Intervention Society.

PMID- 1389772
TI  - Effect of early intravenous heparin on coronary patency infarct size, and
      bleeding complications after alteplase thrombolysis.

PMID- 1389773
TI  - Incessant atrial tachycardia accelerated by pregnancy.

PMID- 1389774
TI  - A note on the anatomy of the supraspinatus muscle.
AB  - The muscles and tendons of the rotator cuff of 37 fixed cadaver shoulder joints
      were dissected. In ten shoulder joints devoid of gross pathological lesions it
      was found that the supraspinatus muscle was inserted at two points--mainly into
      the major tubercle and partly into the lesser tubercle of the humerus. In one
      case of six, an additional insertion clearly occurred in a shoulder joint with
      rotator cuff tear.

PMID- 1389775
TI  - Autogenously vascularised bone allografts. Experimental model of a new bone
      muscle composite graft.
AB  - Conventional bone allografts carry a high incidence of complications such as
      infections and pseudarthroses due to immunological rejection and avascularity of
      grafts. In vascularised grafts healing and remodelling of bone is quicker and
      more complete. However, vascularised allografts need immunosuppression for
      prevention of rejection with vascular occlusion. Autogenously vascularised
      allografts are formed after implantation of bone in muscle of the recipient,
      allowing vascularisation from this muscle. A muscle-bone composite graft is thus
      obtained that can be transferred as a pedicled or free graft with microvascular
      anastomosis. In this study donors were DA and recipients Lewis rats. The bone
      grafts were implanted in the adductor muscles and transferred after 6 weeks into
      a femoral defect. A higher number of osteocytes were found in the autogenously
      vascularised group than in non-vascularised grafts. "Creeping substitution" was
      found in all cortical layers in vascularised grafts, whereas in conventional
      allografts bone resorption predominated. The experimental data suggest that in
      rat autogenously vascularised bone allografts show a remodelling pattern
      comparable with that of conventional vascularised bone autografts. The advantage
      of the autogenously vascularised bone allograft is that it allows transfer of a
      vascularised bone allograft together with its well-vascularised recipient bed
      without immunosuppressive treatment.

PMID- 1389776
TI  - Prostaglandin E2 level in tissue surrounding aseptic failed total hips. Effects
      of materials.
AB  - Production of inflammatory mediators (IM) by cells and specifically macrophages
      around loosened implants may be responsible for their loosening. Our hypothesis
      was that different materials give rise to different amounts of these IM. It is
      thought that alumina/alumina for total hip replacement (THR), which has been used
      for 15 years in our orthopedic department, may produce less IM than other
      systems. We initiated a clinical prospective study to measure the level of
      prostaglandin E2 (PGE2) in tissue surrounding loosened prostheses to quantify
      PGE2 production regarding the types of material involved in the friction couple,
      i.e., alumina/alumina versus metal/polyethylene, and the type of fixation, i.e.,
      cemented versus cementless. A total of 29 THR revisions were performed in 28
      patients. Four implant groups were identified: alumina/alumina cemented,
      alumina/alumina cementless, metal/polyethylene cemented, and metal/polyethylene
      cementless. For each revision, tissues surrounding the failed implants were
      harvested and processed, and the PGE2 was measured in a blind manner using an
      immunoassay technique. As the measuring technique was difficult, at least three
      determinations for each sample were necessary. Some samples were excluded from
      the analysis for various reasons, for example, second or further revisions
      involving many different materials in the past, conjunction of metallic and
      alumina debris and samples taken from non-loosened components. Finally, 15
      samples were considered adequate for inclusion in this study. Two groups were
      analyzed and compared: the alumina/alumina couple and the metal/polyethylene
      couple. Tissue surrounding the first group demonstrated a PGE2 level of 69 +/- 56
      fmol/mg wet weight compared to 202 +/- 156 fmol/mg for the second.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1389777
TI  - Collagen stabilization induced by natural humic substances.
AB  - Humic substances are polyphenolic compounds. They have antiviral as well as
      desmutagenic effects and react with biopolymers such as collagen; thereby they
      have no toxic side effects by oral administration. In vitro incubation with humic
      substances raises the breaking point of the tail tendon of the rat by about 75%.
      The chemical resistance of the collagen fibres in tail tendon collagen is also
      increased by in vitro incubation with humic substances, at least insofar as the
      ultrastructurally and biophysically measurable destruction of the collagen fibres
      by 4 M guanidinium chloride is inhibited. As humic substances increase the
      mechanical and chemical resistance of collagen fibres and promote their
      "maturity", it seems likely that this effect of humic substances depends upon
      their interaction with the hydrogen bonding and covalent bonding of the collagen
      fibres. Such a conclusion is confirmed by the results of X-ray diffraction
      analysis.

PMID- 1389778
TI  - Types I and III procollagen extension peptides in serum respond to fracture in
      humans.
AB  - Markers of types I and III collagen turnover were measured in serial blood
      samples in 16 patients with a Colles' fracture. The collagen markers were the
      carboxy-terminal extension peptide of type I procollagen (PICP) and the amino
      terminal extension peptide of type III procollagen (PIIINP). Significant
      increases were found of PIIINP within 1 week and of PICP within 2 weeks. This
      sequential appearance of PIIINP and PICP was found to be in agreement with the
      appearance of types III and I collagen during early fracture healing as
      demonstrated in previous animal experimental studies. PICP had levelled off after
      9 months, whereas PIIINP remained elevated. Osteocalcin, a serum marker of
      osteoblast activity, increased within 1 week and levelled off after 9 months.
      Correlations between the change in osteocalcin and those in PICP and PIIINP,
      respectively, were weak. These new biochemical markers may prove relevant as non
      invasive markers of normal and pathological fracture healing in humans.

PMID- 1389781
TI  - Range of motion after total condylar knee arthroplasty.
AB  - In this study the function of the knee measured at a medium-follow-up of 5-6
      years was correlated with influencing factors concerning the implant of total
      condylar knee prosthesis in 90 patients. The only variable affecting
      postoperative extension was the preoperative range of extension whereas
      postoperative flexion was influenced by the preoperative flexion, valgus
      deviation of the preoperative AP tibial-femoral angle, position of the patella,
      and thickness of the resection of the distal femur cut.

PMID- 1389779
TI  - Biomechanical analysis of the mechanism of interlocking nail failure.
AB  - From December 1986 to May 1989, 412 patients with 274 femoral and 144 tibial
      fractures were treated with Grosse-Kempf interlocking nails at our hospital. 324
      cases (78.6%) were followed-up for at least 1 year (average 23 months). There
      were 13 breakages in the locking nails in femora and none in tibiae. The recorded
      incidence of breakage in the femur is therefore 4.7% (13/274). The mechanisms of
      locking nail failure are stress concentration around screw hole and nail slot,
      nicking of the nail during drilling of the screw holes, too close proximity of
      the screw hole to the fracture, and larger loading over the proximal femur. The
      incidence of failure is 4.9% in the upper third, 1.9% in the mid-third, and 8.2%
      in the distal third (P greater than 0.05, chi 2 test). The site most at risk is
      the first screw hole of the distal third, especially if it is near the fracture
      site. Prevention of failure involves using a nail of larger diameter and
      sufficient length, improving the surgical drilling technique, and allowing only
      protected weight bearing. Management of nail breakage by insertion of a new
      implant and supplementary cancellous bone grafting can gain satisfactory results.

PMID- 1389780
TI  - Anterior cruciate ligament allograft transplantation for intraarticular
      ligamentous reconstruction.
AB  - A multiplicity of surgical operations have been developed in an attempt to
      achieve satisfactory function after anterior cruciate ligament (ACL) repair. None
      of these procedures have been able to reproduce the fiber organization anatomy of
      attachment site, vascularity, or function of the ACL. Twenty-nine foxhounds
      received a deep-frozen bone-ACL-bone allograft and a ligament augmentation device
      (LAD). Biomechanical, microvascular, and histological changes were evaluated 3,
      6, and 12 months following implantation. The maximum loads of the allograft/LADs
      were 34.3% (387.2 N) after 3 months, 49.3% (556.6 N) after 6 months, and 61.1%
      (698.8 N) after a year. The maximum load was 69.1% (780 N). In general, after 6
      months the allografts showed normal collagen orientation. The allografts
      demonstrated no evidence of infection or immune reaction. No bone ingrowth into
      the LAD was observed. Polarized light microscopy and periodic acid-schiff
      staining showed that the new bone-ligament substance interface had intact fiber
      orientation at the area of the ligament insertion. Microvascular examination
      using the Spalteholtz technique revealed revascularization and the importance of
      an infrapatellar fat pad for the nourishment of ACL allografts.

PMID- 1389782
TI  - Idiopathic Charcot's arthropathy. Report of one case.
AB  - The authors describe a case of idiopathic Charcot's joint in a 67-year-old lady.
      The diagnosis was made after a careful screening that ruled out all the common
      causes, known so far, of Charcot's joint.

PMID- 1389784
TI  - Bilateral scapular fractures secondary to electrical shock.
AB  - Fractures of the scapula are rare injuries. Usually the scapula requires a high
      energy impact to sustain a fracture. Various fractures have been noted as a
      result of convulsive seizures. We report bilateral scapular fractures caused by
      electric shock and discuss their pathomechanical origin.

PMID- 1389783
TI  - Tumoral calcinosis of the ischium.
AB  - The authors report on a case of tumoral calcinosis of the ischium in a 63-year
      old female. By means of this particular case a general review of the literature
      on pathogenesis, histological characteristics, the possible way of treatment and
      the prognosis of tumoral calcinosis is presented.

PMID- 1389786
TI  - Use of a posterior calf fasciocutaneous flap with distal pedicle to reconstruct a
      huge ankle defect.
AB  - A distally based posterior calf fasciocutaneous flap was successfully used to
      reconstruct a major ankle defect with exposed bones and joints. The flap, which
      reaches easily this region, can also be used as a free flap for coverage of heel
      and ankle when the forefoot is not involved in the injury.

PMID- 1389785
TI  - An unusual stress fracture of the fibula in a long-distance runner.
AB  - A stress fracture of the proximal fibula in a young long-distance runner is
      reported. Such fractures are rare. The literature is reviewed and diagnosis and
      treatment are discussed.

PMID- 1389788
TI  - Critical care obstetrics.

PMID- 1389787
TI  - Traumatic hemipelvectomy. A case report and comments on associated injuries.
AB  - The twenty-fifth reported case of survival following traumatic hemipelvectomy is
      presented. Our patient is the fourth female survivor and the second who escaped
      associated injuries to either the genito-urinary system or the rectum.

PMID- 1389789
TI  - Humanizing the intensive care unit experience.
AB  - When the pregnant woman becomes critically ill, it is essential that she and her
      fetus receive the care that a specialized intensive care unit (ICU) provides.
      This unit is the setting for an expert medical, nursing, and technical staff to
      use sophisticated, state-of-the-art equipment for intensive monitoring and the
      immediate life-saving interventions that may be necessary. However, care in an
      ICU sometimes becomes focused on the machinery, rather than on the patient. It is
      imperative that the humanizing aspects of critical care be addressed in caring
      for a pregnant patient and her family. Obstetric critical care can benefit from
      the data in the critical care literature that addresses family and patient needs
      in an ICU. Obstetric literature and past experiences in implementing family
      centered maternity care also can be used to identify the need for humane care and
      to enhance the ICU experience.

PMID- 1389790
TI  - Principles in hemodynamic assessment.
AB  - Use of invasive hemodynamic monitoring provides more thorough assessment of
      hemodynamic function and may reveal abnormal data before the development of
      adverse clinical signs and symptoms. The obstetric nurse caring for critically
      ill patients is responsible for understanding the principles associated with
      hemodynamic monitoring and interpretation of data to better plan and implement
      nursing care.

PMID- 1389791
TI  - Technical aspects of hemodynamic pressure monitoring.
AB  - Invasive hemodynamic pressure monitoring may be used in the care of the
      critically ill pregnant woman. The critical care obstetric nurse must have a
      thorough understanding of the indications for monitoring and interpretation of
      acquired data and must develop the skills necessary to operate and trouble-shoot
      the related equipment. This article provides a review of technical aspects of a
      hemodynamic pressure monitoring system.

PMID- 1389792
TI  - Principles of oxygen transport in the critically ill obstetric patient.
AB  - Invasive hemodynamic monitoring is commonly used in critically ill patients in
      whom cardiorespiratory compromise is evident. The information acquired assists
      the clinician in the assessment of cardiac and intravascular status. However,
      many patients have complex pathophysiologic conditions that dictate the
      evaluation of their oxygen transport system. This article provides a discussion
      of the principles of oxygen transport, including the concepts of oxygen content,
      oxygen affinity, oxygen delivery, and oxygen consumption. Clinicians providing
      care for critically ill pregnant women should have a thorough understanding of
      the physiology of oxygen transport, its alterations in specific disease process,
      and interventions necessary to improve the individual components of oxygen
      transport.

PMID- 1389793
TI  - Mechanical ventilation during pregnancy.
AB  - Mechanical ventilatory support is a significant component in the delivery of
      critical care. With increasing frequency, obstetric critical care nurses face the
      challenge of caring for women who require mechanical ventilation during
      pregnancy. It is important that those caring for such patients understand
      fundamental principles of mechanical ventilation, associated complications, and
      specific nursing care measures.

PMID- 1389794
TI  - Renal dialysis in pregnancy.
AB  - Dialysis may be needed, either acutely or on a chronic basis, during pregnancy
      for a variety of reasons. Advances in erythropoietin, transplant, and hormonal
      therapies may increase the chances of pregnancy in women with chronic renal
      failure. Providing care to this population of patients is a challenge to
      nephrology and obstetric nurses. It is important for the obstetric nurse to
      understand the fundamental principles of dialysis to collaborate in the planning
      and implementation of care for these patients.

PMID- 1389795
TI  - Perinatal hypertensive crisis.
AB  - Women with severe pregnancy-induced hypertension or chronic hypertension with
      superimposed preeclampsia are at risk for the development of hypertensive crisis.
      Hypertensive crisis is an emergent situation that carries great maternal and
      fetal morbidity and mortality. Effective assessment and comprehensive care of the
      patient in hypertensive crisis requires a thorough understanding of the
      underlying disease preeclampsia, common hemodynamic findings, and therapies
      available. Nurses in any perinatal environment must be prepared to respond
      immediately to this critical obstetrical circumstance.

PMID- 1389796
TI  - Pulmonary hypertension.
AB  - Pulmonary hypertension may be primary, of unknown etiology, or secondary to
      existing cardiorespiratory disease. In general, the prognosis is poor, but the
      superimposed physiologic changes of pregnancy, labor, and delivery may produce a
      lethal condition. Pregnancy prevention is better than any proposed care. If
      pregnancy occurs, termination is suggested in the first or early second
      trimesters. If the choice is to continue the pregnancy, a well-coordinated
      intensive management plan is necessary. This plan should include midsecond
      trimester hospital admission of the patient, continuous hemodynamic monitoring
      during the intrapartum period and immediately after delivery, and preferably
      elective induction with hemodynamically stable epidural anesthesia for labor and
      delivery.

PMID- 1389797
TI  - The impact of pregnancy on the woman with congenital heart disease:
      considerations for intrapartum nursing care.
AB  - Many women with congenital heart disease can successfully tolerate the profound
      hemodynamic changes associated with pregnancy and birth with a collaborative team
      approach to management of their disease. This article provides a discussion of
      the interaction between pregnancy and congenital heart disease (including left-to
      right shunts, obstructive lesions, and cyanotic defects), focusing on maternal
      risks and strategies for intrapartum hemodynamic management. Nurses providing
      intrapartum care for women with congenital heart disease must understand the
      applicable cardiac pathophysiology, the risks imposed by pregnancy and the birth
      process, and appropriate medical and nursing interventions to prevent
      complications.

PMID- 1389798
TI  - Myocardial infarction.
AB  - Myocardial infarction (MI) during pregnancy occurs approximately once in 10,000
      pregnancies. The normal cardiovascular alterations associated with pregnancy may
      make the diagnosis of MI difficult. Nursing care focuses on astute assessment
      skills, provision of adequate oxygenation, and prolongation of the healing phase
      to prepare for the stress of delivery. Nurses caring for patients experiencing MI
      during the perinatal period require advanced cognitive knowledge and clinical
      skills to facilitate optimal maternal and fetal outcome.

PMID- 1389799
TI  - Pulmonary edema during pregnancy.
AB  - Physiologic changes in the pulmonary system during pregnancy place the pregnant
      woman at risk for having pulmonary edema. Cardiogenic and non-cardiogenic
      pulmonary edema have similar clinical signs and symptoms; however, treatments may
      differ greatly. Understanding the types of pulmonary edema enables the obstetric
      nurse to provide improved care for this group of patients.

PMID- 1389801
TI  - Amniotic fluid embolism.
AB  - Pulmonary embolism is the leading cause of maternal death in the United States.
      Amniotic fluid embolism (AFE) represents the least preventable and most lethal of
      complications. AFE has a reported mortality of 86% and an associated fetal demise
      of 50%. AFE is widely accepted as a clinical entity but is not completely
      understood. A combination of clinical presentation, laboratory findings, and
      exclusion of other abnormalities leads to the diagnosis of AFE. The mainstays of
      treatment are oxygenation, maintenance of cardiac output, and correction of
      coagulopathy. The prognosis for the patient experiencing AFE remains bleak
      because the course of the disorder is largely unpredictable, and AFE cannot be
      corrected. Only supportive measures can be given.

PMID- 1389800
TI  - Pulmonary embolism.
AB  - A major cause of maternal morbidity and mortality during pregnancy and the
      puerperium is thromboembolic disease. Pregnancy is a hypercoagulative state that
      predisposes the gravida to thrombus formation. Once a thrombus forms in the
      venous system of the lower extremities, it can travel to the pulmonary arterial
      bed, which can lead to hypoxemia or death. Maternal mortality associated with
      pulmonary embolism (PE) is approximately 14%. Most gravidas who have PE during or
      after pregnancy have no history of thromboembolic disease at the time of insult.

PMID- 1389802
TI  - Adult respiratory distress syndrome.
AB  - Adult respiratory distress syndrome (ARDS) is an acute form of noncardiogenic
      respiratory failure that often occurs in previously healthy individuals who have
      sustained severe physiologic insult that is pulmonary or nonpulmonary in origin.
      The perinatal nurse can help increase the survival of the maternal-fetal dyad by
      prompt recognition of the syndrome and early institution of therapeutic measures.

PMID- 1389804
TI  - Neurologic emergencies in pregnancy.
AB  - Neurologic emergencies during pregnancy are not encountered often but contribute
      significantly to maternal mortality. This chapter reviews neurologic emergencies
      with an emphasis on pathophysiology and related nursing care for patients with
      epilepsy, status epilepticus, eclampsia, intracranial hemorrhage, increased
      intracranial pressure, ischemic stroke, myasthenia gravis, autonomic
      hyperreflexia, Wernicke's encephalopathy, and chorea gravidarum.

PMID- 1389803
TI  - Cystic fibrosis in pregnancy.
AB  - Previously considered a pediatric disorder, cystic fibrosis (CF) is becoming a
      more common complication of pregnancy as these patients have increasing life
      expectancies. CF produces profound physiologic alterations in major organ
      systems. These alterations augment the physiologic changes of pregnancy.
      Perinatal nurses can meet the complex needs of these patients by increasing their
      understanding of the disease process, pregnancy-related alterations, and current
      treatment modalities.

PMID- 1389805
TI  - Principles of intracranial pressure monitoring.
AB  - Increased intracranial pressure (ICP) is a life-threatening condition that
      requires immediate recognition and therapeutic intervention. The obstetric nurse
      must have in-depth knowledge of the physiologic changes occurring during
      pregnancy, the relationship between these changes and cerebrovascular accidents,
      and the pathophysiology of increased intracranial pressure to provide the most
      comprehensive nursing care. This chapter describes fundamental principles of
      intracranial pressure monitoring.

PMID- 1389806
TI  - Liver disease in pregnancy.
AB  - This article discusses two liver diseases that are unique to pregnancy: hepatic
      rupture and acute fatty liver of pregnancy. Pathophysiology, signs and symptoms,
      and medical and nursing management during the period of critical illness are
      addressed for both disorders. Although maternal mortality is associated with
      these diseases, women often recover completely after delivery. A major goal of
      medical and nursing management is to support the system until the liver can heal
      and resume the myriad of vital functions for which it is responsible.

PMID- 1389807
TI  - Diabetic ketoacidosis.
AB  - Diabetic ketoacidosis (DKA) is a form of decompensated diabetes. When it occurs
      during pregnancy, it may lead to maternal and fetal morbidity and mortality. DKA
      is defined by accelerated gluconeogenesis and ketogenesis and occurs most often
      in the presence of one of four predisposing factors: insulin deficiency (absolute
      or relative); excess counter regulatory hormones; fasting; and dehydration.
      Infection is a common catalyst. Once the disorder is diagnosed, intensive
      obstetrical nursing care is required. The principles of management include
      rehydration, insulin therapy, electrolyte replacement, and identification and
      treatment of the underlying cause. A plan for assessment of the pregnant patient
      with diabetes and in DKA and treatment guidelines are presented.

PMID- 1389809
TI  - Disseminated intravascular coagulation.
AB  - In normal hemostasis, a balance exists between coagulation and fibrinolysis.
      Disseminated intravascular coagulation (DIC) is a condition characterized by the
      excessive formation of fibrin clots; it involves all aspects of the coagulation
      system. In view of its potential for major morbidity and mortality, an
      understanding of the disorder is essential. Management of DIC in pregnancy should
      include removal of the triggering mechanism and aggressive blood and fluid
      replacement.

PMID- 1389808
TI  - Trauma during pregnancy.
AB  - The active roles assumed by most pregnant women today put them at risk for
      vehicular accidents, falls, industrial accidents, violence, and other injuries.
      Trauma during pregnancy increases the maternal and fetal mortality and morbidity
      risks. Knowledge of the physiology of pregnancy is essential to establishing
      priorities and providing optimum care for the woman and fetus. Assessments and
      care from trauma and obstetric perspectives are essential; however, treatment
      priorities for the pregnant trauma patient are the primary consideration and are
      identical to those for nonpregnant trauma patients. Pregnancy does not limit or
      restrict any resuscitative, diagnostic, or pharmacologic treatment indicated
      after trauma. Fetal survival is dependent on maternal survival, so the woman must
      receive immediate intervention and condition stabilization for optimum fetal
      outcome.

PMID- 1389810
TI  - Cardiopulmonary resuscitation during pregnancy.
AB  - Cardiopulmonary arrest during pregnancy, although relatively rare, poses a unique
      challenge to the obstetric nurse. Resuscitation measures attempt to restore
      maternal hemodynamic stability and promote fetal well-being. Prognosis is
      improved when those caring for such women possess the knowledge and skills
      necessary to implement basic and advanced resuscitation protocols. This chapter
      reviews significant physiologic alterations in pregnancy that have an impact on
      resuscitation and cardiopulmonary resuscitation (CPR) algorithms for selected
      pulseless rhythms. As critical care capabilities continue to develop within
      obstetric units, it is reasonable to predict that obstetric nurses will face this
      challenge with increasing frequency.

PMID- 1389811
TI  - Prolonged postoperative oxygen therapy.

PMID- 1389812
TI  - Pain sensation and nociceptive reflex excitability in surgical patients and human
      volunteers.
AB  - Pain threshold, nociceptive flexion reflex (NFR) threshold and responses to
      suprathreshold stimulation were investigated in 15 female patients (mean age 32
      yr (range 22-48 yr)) before and 68 (range 48-96) h after gynaecological
      laparotomy. Control measurements were performed in 17 healthy human volunteers
      (five males, age 30 yr (range 24-41 yr)). In the surgical patients, pain
      threshold decreased and pain to suprathreshold stimulation increased
      significantly (P = 0.006 and P = 0.04, respectively) from before to after
      surgery. A corresponding trend was demonstrated in neurophysiological
      measurements, although the decrease in NFR threshold and increase in NFR
      amplitude to suprathreshold stimulation were not significant (P = 0.08 and P =
      0.24, respectively). The correlations between the relative change in pain and
      reflex thresholds, and time from surgery, were statistically significant (pain
      threshold: rs = 0.53, P = 0.04; NFR thresholds: rs = 0.54, P = 0.04). In the
      healthy volunteers, no significant differences in thresholds and responses to
      suprathreshold stimulation were observed between two recordings with an interval
      of at least 48 h. The allodynia and hyperalgesia observed in postsurgical
      patients may be related to postoperative sensitization of central neurones.

PMID- 1389813
TI  - Auditory evoked response and awareness: a study in volunteers at sub-MAC
      concentrations of isoflurane.
AB  - We have investigated the relationship between the auditory evoked response (AER)
      and simple tests of conscious awareness at four end-expiratory concentrations
      (0.0, 0.1, 0.2 and 0.4 MAC) of isoflurane in oxygen in each of eight anaesthetist
      volunteers, in random order, at least 1 week apart. The early cortical AER was
      recorded from electrodes at the vertex and inion. Amplitudes of the waves Pa, Nb
      and Pc and latencies of the waves Na, Pa, Nb, Pb and Nc were measured. All the
      AER variables were highly significantly related to end-expiratory anaesthetic
      concentration. Amplitudes decreased and latencies increased progressively with
      increasing anaesthetic concentration. The AER variables were also highly
      significantly related to the level of response. Amplitudes were greatest and the
      latencies shortest when there was full response to command. (Nb latency increased
      from 47.5 to 54.5 ms between partial and no response.) The close correlation
      between the effects of concentration and level of response, and between
      concentration and the AER implied that it was difficult to demonstrate those
      changes in the AER which specifically relate to changes in response. At 0.2 MAC,
      however, which was the concentration at which all subjects showed some deficit,
      the response to a shock word was distinguished clearly by Nb latency. In eight of
      24 possible comparisons (eight AER variables and three types of psychological
      test) the AER fitted the response more closely than concentration.

PMID- 1389814
TI  - Some effects of isoflurane on I waves of the motor evoked potential.
AB  - We have investigated the effects of isoflurane anaesthesia on the motor evoked
      potential recorded in the extradural space during corrective spinal surgery in 15
      patients. Isoflurane was added to a nitrous oxide in oxygen mixture supplemented
      with fentanyl and a neuromuscular blocking agent. Isoflurane was administered to
      achieve end-tidal concentrations of 2%, 1% and 0% in all patients, and also of
      1.5% and 0.5% in nine patients. Transcranial electrical stimulation of the motor
      cortex was used to elicit descending volleys in corticospinal axons (the motor
      evoked potential). With stimuli of 450-750 V and no isoflurane, multiple I waves
      were always seen following the D wave. In all patients the number of I waves
      decreased and individual I waves became smaller in amplitude the greater the
      isoflurane concentration, but there were only minor changes in the D wave. The
      greatest depressant effect on I waves occurred at an end-tidal concentration of
      0.5%. Given that I waves are an index of synaptic transmission, anaesthetic
      induced changes in I waves may provide a useful model for the neuronal events
      underlying anaesthesia-induced unconsciousness.

PMID- 1389815
TI  - Risk factors for oxygen desaturation during sleep, after abdominal surgery.
AB  - The postoperative period after major abdominal surgery is known to be a period of
      increased episodic oxygen desaturation. In order to assess the risk factors for
      episodic desaturation, we have studied 29 surgical patients using pulse oximetry
      during the preoperative night (Npre) when they received benzodiazepine
      premedication and breathed air, and also during the first three nights after
      operation when they received nasal oxygen supplementation. Modal oxygen
      saturation (SpO2) exceeded 95% during all nights studied. The time spent at less
      than 90% (t90) and 85% (t85) SpO2 and the average SpO2 nadir (SpO2, nadir) did
      not differ each night. Heart rate was greater (mean 90.1 (SD 16.6) vs 68.2 (12.0)
      beat min-1, P < 0.001) during the second night after operation (N2) than during
      Npre. Before operation, the number of desaturations, t90 and t85 correlated with
      pharyngeal hypertrophy (P = 0.003, P = 0.002, P = 0.001, respectively). At the
      same time, t90 and t85 correlated with body mass index (P = 0.02 and P = 0.05,
      respectively). During N2, t90 correlated with radiological lung consolidation (P
      = 0.05) and SpO2, nadir correlated with FEV1 (P = 0.03). We conclude that there
      are several mechanisms responsible for oxygen desaturation and that these
      mechanisms differ before and after surgery.

PMID- 1389816
TI  - Effect of speed of injection of 0.5% plain bupivacaine on the spread of spinal
      anaesthesia.
AB  - We have studied the influence of two different speeds of injection on the spread
      of spinal anaesthesia of bupivacaine in 40 orthopaedic patients. In a random
      order, 0.5% plain bupivacaine 3 ml was administered in 10 or 180 s into the
      subarachnoid space using a 27-gauge needle with the patients in a lateral
      horizontal position. The slower speed produced a higher spread of spinal
      anaesthesia (median difference 2.5 segments, P < 0.05).

PMID- 1389817
TI  - Elimination of bupivacaine and pethidine from the rabbit feto-placental unit.
AB  - Bupivacaine 12.5 mg and pethidine 12.5 mg were administered as an i.v. infusion
      over 80 min in 15 near-term pregnant New Zealand white rabbits. After the
      infusion, pups were removed via individual hysterotomies every 30 min.
      Bupivacaine and pethidine were measured by gas chromatography in amniotic fluid,
      placenta, fetal plasma, fetal brain and maternal plasma, sampled as each fetal
      sac was opened. Pethidine was cleared from all compartments more rapidly than
      bupivacaine and for both drugs elimination rates were maternal plasma > placenta
      > amniotic fluid > fetal brain > fetal plasma. Concentrations of both drugs in
      fetal plasma correlated significantly only with those in fetal brain and not with
      those in maternal plasma, placenta or amniotic fluid, while there were positive
      correlations between the last three compartments. Nested analysis of covariance
      showed that only maternal plasma and placental concentrations of the two drugs
      decreased significantly with time. Maternal plasma half-lives for pethidine and
      bupivacaine were 1.0 and 2.0 h, and placental half-lives 1.9 and 2.5 h,
      respectively. The apparent fetal plasma half-life of pethidine was 9.9 h while
      there was apparently no net elimination of bupivacaine from fetal plasma.

PMID- 1389818
TI  - Comparison of the maternal and fetal effects associated with intermittent or
      continuous infusion of extradural analgesia.
AB  - Eighty normal primigravidae received an extradural dose of 0.25% bupivacaine and
      were then allocated randomly to receive "top-ups" of 0.25% bupivacaine (group A)
      or an infusion of 0.125% bupivacaine (group B). Group B received supplementary
      top-ups if required. Group A required more top-ups (147 vs 80) (P < 0.01). No
      maternal advantage was demonstrated from each regimen. Fetal state was assessed
      by analysis of the cardiotocograph during labour and the condition of the fetus
      at delivery. Three different patterns of late deceleratory episodes were
      identified (grades 1-3). Total numbers of episodes per group were similar (group
      A, 71; group B, 69). More episodes in group A were related to top-ups (42/71 vs
      18/69; P < 0.01) but the incidence of episodes after a top-up was similar (group
      A, 42/147 (28.6%); group B, 18/80 (22.5%)). In group A, 31/42 events (73.8%) were
      transient compared with 11/18 persistent episodes (61.1%) (> 10 min duration) in
      group B. However, the difference in the deceleratory patterns did not influence
      the condition of the fetuses at delivery.

PMID- 1389819
TI  - Thrombelastography after aspirin ingestion in pregnant and non-pregnant subjects.
AB  - The thrombelastograph (TEG) and bleeding time were performed before and 6 h after
      a single oral dose of aspirin 600 mg in a group of eight healthy volunteers and
      12 pregnant patients. Measured TEG variables (r, k, r+k times and maximum
      amplitude) were unaltered after aspirin although there was a significant
      prolongation of the bleeding time in both groups. Although the TEG appeared not
      to detect aspirin-induced changes in platelet function, the TEG measures all
      phases of coagulation and the unaltered TEG after aspirin suggested a functioning
      coagulation system.

PMID- 1389820
TI  - Hypnotic and anaesthetic interactions between midazolam, propofol and alfentanil.
AB  - We have examined interactions between midazolam, propofol and alfentanil using
      two end-points of light sedation (hypnosis) and anaesthesia. Quantal dose
      response curves were determined in 400 female patients for the drugs individually
      and in combination. At the hypnotic end-point, interactions were analysed by
      fitting the data to a mathematical model where the response depended on the doses
      of the three drugs with additional terms included to describe non-additive
      interactions of the various combinations of the three drugs. There were
      significant interactions for hypnosis; the decrease in expected ED50 for the
      various combinations were: midazolam-propofol = 37%, midazolam-alfentanil = 46%,
      propofol-alfentanil = 20%, midazolam-propofol-alfentanil = 42%. Whilst all
      responses to the two-drug combinations were synergistic, the three-drug
      combination led to a response that was less than that expected from the effects
      of the individual agents and their two drug interactions. For anaesthesia, dose
      related effects could not be demonstrated for midazolam or alfentanil when used
      alone. The decrease in ED50 of propofol in the presence of the other compounds
      was propofol-midazolam = 52%, propofol-alfentanil = 73%, propofol-midazolam
      alfentanil = 82%. When comparing the different combinations, the responses varied
      markedly at each end-point assessed and could not be predicted from the responses
      of the individual agents.

PMID- 1389821
TI  - Pharmacodynamic stability of a mixture of propofol and alfentanil.
AB  - We studied 40 patients undergoing body surface surgery in a double-blind manner
      to compare the pharmacodynamic stability of either mixed or separate infusions of
      propofol and alfentanil. No differences were found between the two groups in
      respiratory or cardiovascular variables during operation, or in requirements for
      analgesia after operation. The power of the study to determine a difference of 10
      mm Hg in mean arterial pressure with a probability of 0.05 was 0.82 and for a
      difference of 1 kPa in end-tidal carbon dioxide partial pressure 0.89. We
      conclude that propofol and alfentanil may be administered by infusion from a
      single syringe without diminished or delayed effect of the opioid during
      anaesthesia and the first 4 h after operation.

PMID- 1389822
TI  - Changes in cardiac index and estimated systemic vascular resistance during
      induction of anaesthesia with thiopentone, methohexitone, propofol and etomidate.
AB  - Changes in cardiac index (CI) and estimated systemic vascular resistance (ESVR)
      were assessed non-invasively using pulsed Doppler ultrasound during induction of
      anaesthesia. Ninety-six ASA I patients were allocated randomly to one of four
      groups to receive alfentanil 8 micrograms kg-1 followed by a dose of thiopentone,
      methohexitone, propofol or etomidate sufficient to obtund the eyelash reflex. CI
      increased significantly by 8% 1 min after administration of both methohexitone (P
      < 0.05) and propofol (P < 0.05), returning to pre-induction values thereafter. CI
      increased after thiopentone but the increase was not statistically significant.
      There was a significant decrease in CI of 16% after induction with etomidate (P <
      0.001). ESVR decreased significantly from pre-induction values by 18% after
      methohexitone (P < 0.001) and 23% after propofol (P < 0.001). ESVR in the
      thiopentone group decreased, but this was not statistically significant. ESVR
      increased significantly by 12% 1 min after induction of anaesthesia with
      etomidate (P < 0.05) and then decreased towards pre-induction values. The results
      suggest that the cardiostability of etomidate may not be as complete in all
      groups of patients as previous studies have suggested.

PMID- 1389823
TI  - Propofol anticonvulsant activity in experimental epileptic status.
AB  - We have examined the anticonvulsant properties of propofol in high doses in two
      experimental models of status epilepticus: generalized pentylenetetrazol (PTZ)
      induced seizures and partial, cortically applied penicillin G-induced seizures.
      Propofol was administered either as a single bolus injection or as a bolus
      injection followed by an infusion for 1 h. When administered as a single bolus
      injection, propofol 12 mg kg-1 suppressed electrical and clinical seizures in PTZ
      generalized epileptic status, and an infusion of 50 mg kg-1 h-1 prevented the
      reappearance of electrical and clinical signs. In focal epileptic status, the
      single dose stopped paroxysmal activity and the associated clonic jerks for a few
      seconds. When the bolus dose was followed by an infusion, the firing bursts were
      replaced by isolated spikes, and contralateral jerks became sporadic and feeble.
      The greater efficacy of propofol against PTZ convulsions may be a reflection of
      the opposite action of the two drugs on neural membrane conductance: PTZ induces
      paroxysmal neural discharge by enhancing membrane conductance while propofol
      appears to decrease membrane conductance, thus suppressing paroxysmal discharge.
      There was no close relationship between blood concentration of the anaesthetic
      and its clinical effects, at least after a short-term infusion, as used in the
      present experiments. We suggest that propofol may be a potentially useful drug in
      status epilepticus in patients in whom benzodiazepines, barbiturates and
      phenytoin have failed.

PMID- 1389824
TI  - Advances in cardiopulmonary resuscitation.

PMID- 1389825
TI  - Video surveillance of oxygen administration by mask in postoperative patients.
AB  - Patients may not receive prescribed oxygen because the oxygen face mask becomes
      displaced. Using video, we have observed the position of the face mask in 20
      postoperative patients and recorded the timing and the events associated with
      mask displacement. Correct placement of the mask was confirmed at the start of
      the 8-h study period from 22:00 on the first night after operation. The mask
      remained on continuously and positioned correctly in only one patient. In the
      other 19 patients, it was removed 64 times (range 1-10 times per patient). The
      mask was removed 45 times for nursing tasks such as mouth care and temperature
      measurement and these represented 70% of the total number of times that the mask
      was not in position. Other reasons for removal were vomiting, retching and
      removal by the patient. The mask remained off a median time of 6 min 55 s per
      episode (range 46 s to 7 h 46 min 57 s) and per patient a median of 1 h 6 min 48
      s (range 1 min to 7 h 46 min 57 s). Mask removal resulted in an average decrease
      in oxygen saturation of 4%. Oxygen by mask at 4 litre min-1 maintained an average
      saturation > or = 95% in most, but not all, of the patients.

PMID- 1389826
TI  - Learning during general anaesthesia: implicit recall after methohexitone or
      propofol infusion.
AB  - Forty-four patients undergoing coronary artery surgery were allocated randomly to
      receive an infusion of propofol or methohexitone as a hypnotic supplement to a
      fentanyl-based anaesthetic technique. A taped message was played to the patients,
      consisting of 10 words associated with prompt sentences and a suggestion for a
      specific postoperative behavioural response. Twenty patients (10 propofol and 10
      methohexitone) (perioperative group) were exposed to the taped message during
      surgery and in the immediate postoperative period and the other 24 patients
      (postoperative group) were exposed to the tape only in the postoperative period,
      after return to the intensive care unit (ICU). No patient had explicit recall of
      any events during the period when the tape was played. The patients in the
      propofol group who heard the tape during surgery had significant implicit recall
      of the word associations compared with the equivalent 10 methohexitone patients
      (P = 0.004), when tested 48 h after surgery. The patients who were played the
      tape whilst receiving identical infusion regimens for sedation in the ICU did not
      demonstrate implicit recall of the word associations in either the propofol or
      the methohexitone groups. There was no evidence of a response to the specific
      behavioural suggestion during the postoperative interview. The results confirm
      that auditory perception can occur during clinically adequate anaesthesia, and
      that suppression of auditory awareness or learning is a function of both the
      pharmacological degree of sedation and the degree of surgical stimulation.

PMID- 1389827
TI  - The importance of activity and pretreatment in the prevention of suxamethonium
      myalgias.
AB  - We have studied the effectiveness of pretreatment with atracurium 0.05 mg kg-1
      and placebo before administration of suxamethonium, in the prevention of
      postoperative myalgia in inpatients having surgery in which rapid postoperative
      mobilization was possible (vaginal hysterectomy). On the second day after
      operation, the patients pretreated with atracurium had significantly fewer
      postoperative myalgias than those receiving placebo (P < 0.025). All patients
      were significantly more active on the second day compared with the first day
      after operation (P < 0.025). Possible causal relationships are discussed.

PMID- 1389828
TI  - Training in fibreoptic tracheal intubation in the north of England.
AB  - Twenty-nine departments of anaesthesia in the North of England were questioned
      about the availability and teaching of fibreoptic tracheal intubation techniques.
      While 27 departments had both suitable equipment and trained consultant staff,
      only one offered formal teaching to all its junior anaesthetists.

PMID- 1389829
TI  - Skin injury in an infant with pulse oximetry.
AB  - An 11-month-old girl received 23 propofol anaesthetics for radiation treatment of
      a retinoblastoma. After the first two anaesthetics, a skin injury appeared on the
      pulp of the toes, where the light source of a pulse oximeter probe had been
      placed. During the remaining 21 anaesthetics the light source of the probe was
      placed over the nails, and no other skin lesions occurred. Examination of the
      equipment revealed no malfunction. Thermal and other possible causes of the skin
      injury are discussed.

PMID- 1389830
TI  - Recognition and management of difficult airway problems.

PMID- 1389831
TI  - Recognition and management of difficult airway problems.

PMID- 1389832
TI  - Recognition and management of difficult airway problems.

PMID- 1389833
TI  - Verapamil and cardiovascular responses to tracheal intubation.

PMID- 1389835
TI  - Oxygen wastage by oxygen-air mixers.

PMID- 1389834
TI  - Bedside respiratory measurements with the Siemens-Elema CO2 analyzer.

PMID- 1389836
TI  - A national database on hepatitis after exposure to inhaled halothane.

PMID- 1389837
TI  - Cardiovascular responses to tracheal extubation.

PMID- 1389838
TI  - The role of prostaglandins in the control of renal function.

PMID- 1389839
TI  - Sternocleidomastoid muscle contractility at different levels of isoflurane
      anaesthesia in humans.
AB  - We have measured force-frequency curves of the sternocleidomastoid muscle in six
      patients at three different levels of isoflurane anaesthesia (1.0, 1.4 and 1.8
      MAC). Spontaneous ventilation was suppressed by mild hypocapnia induced by
      mechanical ventilation. An anterior force vector of the sternocleidomastoid
      muscle was measured during isometric contraction induced by supramaximal
      electrical stimulation at 20, 50 and 100 Hz to the i.m. accessory nerves of the
      muscle. The force response at 20 Hz and 50 Hz did not change with an increase in
      isoflurane concentration, but it decreased at 100 Hz as isoflurane concentration
      increased. The reduction in the force at 100 Hz may be caused mainly by impaired
      neuromuscular transmission.

PMID- 1389840
TI  - Synergistic interaction between midazolam and propofol.
AB  - We gave either midazolam or propofol for induction of anaesthesia to 140 ASA I or
      II female patients (18-60 yr). ED50 values were obtained by probit analysis for
      three clinical end-points: loss of response to command; loss of eyelash reflex;
      failure to respond to application of an anaesthetic face mask delivering 1%
      isoflurane. Propofol ED50 values (95% confidence intervals) were 1.25 (0.99-1.48)
      mg kg-1, 1.61 (1.29-1.94) mg kg-1 and 1.51 (1.20-1.82) mg kg-1, respectively.
      ED50 values for midazolam were 0.26 (0.20-0.37) mg kg-1, 0.29 (0.23-0.47) mg kg-1
      and 0.25 (0.20-0.32) mg kg-1, respectively. An additional 92 similar patients
      received one of nine dose combinations of midazolam and propofol for induction of
      anaesthesia, propofol being administered 2 min after midazolam. Success of
      induction was based on the clinical end-point of loss of response to command.
      Administration of 25% of the ED50 of midazolam followed by 50% of the ED50 of
      propofol resulted in loss of response to command in 50% of patients, while 50% of
      the ED50 of midazolam, followed by 25% of the ED50 of propofol had the same
      effect. A probit regression model specifying a synergistic interaction between
      midazolam and propofol fitted the data significantly better than a model
      specifying no interaction.

PMID- 1389841
TI  - EEG and memory effects of low-dose infusions of propofol.
AB  - The purpose of this study was to identify EEG changes associated with low-dose
      propofol infusion producing only sedative effects, and to describe the memory
      effects of low-dose propofol infusion. Ten healthy volunteers underwent EEG
      monitoring (at Fz, Cz, Pz and Oz electrode sites) before, during and after
      propofol 0.5 mg kg-1 i.v. bolus and 75 micrograms kg-1 min-1 as an infusion. Mean
      serum concentration of propofol during infusion was 0.86 (SD 0.14) micrograms ml
      1. The EEG changed significantly during infusion, with increased power in the
      beta 1 (15-20 Hz), beta 2 (20.5-30 Hz) and delta (1-3.5 Hz) frequencies. Beta 1
      and beta 2 power changes were most marked at the Fz and Cz electrodes. Subjects
      were sedated, but able to complete cognitive tasks. Visual analogue scales of
      attention and sleepiness were obtained throughout the study and demonstrated a
      sedative effect during propofol infusion, but were not a significant factor in
      memory performance or EEG changes. A verbal learning task (Rey Auditory-Verbal
      Learning Task) administered before, during and after infusion showed a marked
      reduction in short-term memory capacity and dramatically impaired free recall and
      recognition during infusion. Nine of 10 subjects had partial amnesia for complex
      visual scenes presented during infusion, recalling less than 50% of the material.
      Stronger cueing was required to retrieve information presented during propofol
      infusion, with an increase in mean retrieval time from 95.4 (41.2) s to 426.8
      (83.1) s. EEG and memory effects resolved quickly after the end of
      infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389842
TI  - Recovery of cognitive functions after anaesthesia with desflurane or isoflurane
      and nitrous oxide.
AB  - We studied recovery in 25 adult patients, ASA I, undergoing elective orthopaedic
      procedures after anaesthesia with 0.65 MAC desflurane (n = 16) or isoflurane (n =
      9) with 60% nitrous oxide in oxygen. Early emergence from anaesthesia was
      assessed in the operating room by measuring time to spontaneous movement, cough,
      response to painful pinch, tracheal extubation, opening of the eyes and stating
      correct age, name and body parts. The return of cognitive functions in the late
      recovery phase was assessed in the post-anaesthesia care unit (PACU) by post
      anaesthesia recovery scores (PARS), the Trieger dot test (TDT), and the digit
      substitution test (DST). In the early recovery phase, time to tracheal
      extubation, opening eyes, telling correct name, age and body parts occurred
      significantly faster in the desflurane group than in the isoflurane group (P <
      0.05). The mean "triple orientation" time (to name, age, body parts) was 10.9
      (SEM 0.9) min for desflurane, compared with 18.6 (2.5) min for isoflurane (P <
      0.01). In the late recovery phase, desflurane patients had significantly greater
      PARS, more correct responses to the DST and fewer error responses to the TDT.
      Recovery times were not increased by increased duration of desflurane
      anaesthesia. The desflurane patients showed no delirium, minimal sedation and
      less shivering during the entire postoperative course. We conclude that
      desflurane anaesthesia was superior to isoflurane anaesthesia, not only in
      emergence, but also in the recovery of cognitive functions.

PMID- 1389843
TI  - Blood concentrations of sevoflurane and isoflurane on recovery from anaesthesia.
AB  - We studied 16 healthy ASA physical status I patients (aged 13-71 yr for
      sevoflurane and 22-74 yr for isoflurane) to determine maximum blood
      concentrations on awakening (MBCawake) from sevoflurane and isoflurane
      anaesthesia, and determined if age and duration of anaesthesia significantly
      influenced MBCawake. After operation, the end-tidal concentration of anaesthetics
      was decreased gradually. During recovery from anaesthesia, patients were asked
      repeatedly to open their eyes. We obtained blood samples to measure the
      anaesthetic concentration when patients first opened their eyes. MBCawake of
      sevoflurane and isoflurane (ml of anaesthetic gas per ml of blood) were 0.40 (SE
      0.04)% and 0.53 (0.04)%, respectively. MBCawake values of sevoflurane and
      isoflurane correlated significantly with age (P < 0.05) but not with duration of
      anaesthesia. Blood:gas partition coefficients of sevoflurane and isoflurane were
      0.65 (SD 0.05) and 1.36 (0.09), respectively. There was no significant
      correlation between age and blood:gas partition coefficient for sevoflurane and
      isoflurane. Awakening alveolar concentrations (MACawake) calculated from MBCawake
      were 0.61 (SE 0.05)% for sevoflurane and 0.39 (0.02)% for isoflurane, and
      correlated significantly with age. The ratios of awakening alveolar concentration
      to MAC were reasonably constant--0.33 for sevoflurane and 0.33 for isoflurane.

PMID- 1389844
TI  - Effect of ketanserin on global cerebral blood flow and cerebral oxygen metabolism
      during midazolam-fentanyl or isoflurane anaesthesia.
AB  - We have studied the effect of ketanserin on cerebral blood flow (CBF), cerebral
      oxygen metabolism (CMRO2) and cerebrovascular carbon dioxide reactivity in 19
      adult patients undergoing lumbar disc operation--10 during midazolam-fentanyl
      anaesthesia (group A) and nine during isoflurane anaesthesia (group B).
      Measurements were made in each patient whilst awake, during anaesthesia, during
      anaesthesia with ketanserin and during anaesthesia with ketanserin and
      hyperventilation. CBF was measured by the i.v. xenon-133 technique. CMRO2 was
      calculated as the product of CBF and the cerebral arterio-venous oxygen content
      difference. In the awake state, CBF was 52 and 51 ml/100 g min-1 and CMRO2 3.8
      and 3.5 ml/100 g min-1 in groups A and B, respectively. After induction of
      anaesthesia, CBF decreased 37% in group A and 22% in group B (P < 0.05); CMRO2
      decreased 26% in group A and 51% in group B (P < 0.05). Adding ketanserin did not
      change CBF or CMRO2 in either group. The carbon dioxide reactivity of the
      cerebral vessels during anaesthesia with ketanserin was 15.4% kPa-1 in group A
      and 24% kPa-1 in group B. We concluded that ketanserin, in a clinically
      recommended dose, administered during midazolam-fentanyl or isoflurane
      anaesthesia had no effect on global CBF, CMRO2 or the relationship between the
      two factors. Cerebrovascular carbon dioxide reactivity was preserved.

PMID- 1389845
TI  - Comparison of intubating conditions after administration of Org 9246 (rocuronium)
      and suxamethonium.
AB  - We have assessed intubating conditions after administration of Org 9426
      (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients
      anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of
      fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1
      in similar groups of patients. The influence of prior suxamethonium
      administration on the potency of Org 9426 was studied also by constructing a dose
      response curve. Intubating conditions after Org 9426 were found to be clinically
      acceptable (good or excellent) in 95% of patients at 60 s and in all patients at
      90 s and in all patients at both times after suxamethonium. The average time for
      the onset of block following Org 9426 at this dose was 89 s (which is shorter
      than with any of the currently available non-depolarizing neuromuscular blocking
      drugs); the duration of clinical relaxation (25% recovery of twitch height) 30
      min. Prior administration of suxamethonium did not appear to influence the
      potency of Org 9426.

PMID- 1389847
TI  - Effect of dobutamine on oxygen supply and uptake in healthy volunteers.
AB  - We have measured the changes in VO2 and the VO2:DO2 relationship during infusion
      of dobutamine in healthy volunteers. Nine healthy, adult, non-obese, male
      physicians were infused with an incremental infusion of dobutamine starting at
      2.5 micrograms kg-1 min-1 increasing to 5.0 and then 7.5 micrograms kg-1 min-1
      for 15 min each. VO2 and cardiac index were measured every five minutes. VO2I
      (VO2m-2) increased from a baseline of 128 (SEM 6.1) ml min-1 m-2 to 159 (8.0) ml
      min1 m-2 (P < 0.05) at the end of infusion with 7.5 micrograms kg-1 min-1. The
      corresponding changes for DO2I (DO2 m-2) were from 643 (35) ml min-1 m-2 to 1240
      (142) ml min-1 m-2 (P < 0.05). The coefficient of correlation for pairs of VO2
      and DO2 values, at baseline and each dobutamine infusion in individual subjects,
      ranged from 0.89 to 0.99 (mean 0.95, SD 0.03). Dobutamine has potent calorigenic
      effects; demonstration of a positive correlation between VO2 and DO2 after
      infusion of dobutamine does not necessarily imply an underlying tissue oxygen
      debt.

PMID- 1389846
TI  - Hepatotoxicity testing of atracurium and laudanosine in the isolated, perfused
      rat liver.
AB  - The pharmacokinetics of atracurium, which is degraded by Hofmann decomposition
      and ester hydrolysis, is not altered by impaired liver function. Atracurium
      should, therefore, be ideal for patients with heptic failure, and is now widely
      used in clinical practice. However, some studies reported considerable
      hepatotoxicity after atracurium, especially from its breakdown products--for
      example, leakage of lactate dehydrogenase (LDH) from isolated rat hepatocytes.
      Therefore, we have studied, in an isolated perfused rat liver model, biochemical
      and morphological changes after administration of either atracurium or its main
      metabolite, laudanosine. Despite using extremely high concentrations of these
      substances, we could not detect, biochemically (release of LDH or aspartate amino
      transferase (AST)) or histologically, any signs of liver cell damage.

PMID- 1389849
TI  - Thrombelastography.

PMID- 1389848
TI  - Indomethacin in the management of postoperative pain.
AB  - We have examined the analgesic effects of indomethacin in a double-blind study of
      56 patients undergoing surgery for lumbar disc prolapse. The patients were
      allocated randomly to receive either indomethacin 100 mg i.v. before surgery,
      followed by 100 mg rectally 6 and 12 h after surgery and at 08:00, 16:00 and
      23:00 on the next day, or placebo. Postoperative pain was assessed using a 10-cm
      visual analogue scale at fixed times. Side effects and consumption of
      supplementary analgesics were recorded. Patients receiving placebo had
      significantly greater pain scores and significantly more patients in the placebo
      group required supplementary analgesics.

PMID- 1389850
TI  - Regurgitation of gastric contents during general anaesthesia using the laryngeal
      mask airway.
AB  - We have investigated the incidence of regurgitation of gastric contents during
      general anaesthesia administered via a laryngeal mask airway (LMA) or face mask
      and Guedel airway in 56 patients with no risk factors for regurgitation. Patients
      swallowed a gelatin capsule containing methylene blue 10 min before induction of
      anaesthesia. Fibreoptic laryngoscopy in the LMA group or conventional
      laryngoscopy in the face mask group was performed at the end of surgery. Dye was
      observed within the laryngeal mask in seven of 28 patients (25%). No patients in
      the face mask-Guedel airway group regurgitated dye (P = 0.005). There was no
      evidence of aspiration of dye.

PMID- 1389851
TI  - Pain on injection of propofol: comparison of lignocaine with metoclopramide.
AB  - We have conducted a randomized, double-blind study in 255 ASA I and II patients
      to compare the efficacy of lignocaine and metoclopramide in minimizing the pain
      of injection of i.v. propofol. When administered immediately before propofol into
      a dorsal hand vein, compared with placebo both drugs significantly reduced the
      incidence of pain on subsequent injection of propofol (P < 0.001). Twenty
      patients who had received metoclopramide (n = 85) experienced pain, compared with
      18 who had received lignocaine (n = 85) and 42 who had been pretreated with
      saline (n = 85).

PMID- 1389852
TI  - Comparison of the use of the laryngeal mask and face mask by inexperienced
      personnel.
AB  - Ten junior doctors with no postgraduate anaesthetic experience attempted to
      ventilate the lungs of 50 anaesthetized patients, using either a laryngeal mask
      or a Guedel airway and face mask. Success was defined as the production of two
      successive tidal volumes exceeding 800 ml within 40 s. The failure rate was
      significantly greater using the laryngeal mask compared with the face mask (P <
      0.05) and the average time was significantly longer with the laryngeal mask than
      with the face mask (P < 0.01). The results from this investigation suggest the
      laryngeal mask airway cannot be recommended as a resuscitation device for use by
      inexperienced operators.

PMID- 1389853
TI  - Fatal tracheal compression after haemorrhage into the axilla.
AB  - We report a case of fatal ventilatory obstruction as a result of haemorrhage into
      the axilla after a comminuted spiral fracture of the upper one-third of the
      humerus. Guidelines are presented as to the early recognition of such
      complications and their subsequent management.

PMID- 1389854
TI  - Anaphylactoid or carcinoid?
AB  - A patient with a carcinoid tumour and a history suggestive of carcinoid syndrome,
      but with no biochemical evidence in support, had a cardiovascular collapse during
      an anaesthetic with propofol and suxamethonium. Subsequent investigations
      suggested an anaphylactoid reaction to suxamethonium, but there were features in
      common with a carcinoid crisis. The necessity for a second anaesthetic soon
      afterwards posed a dilemma. In the event of a similar reaction during another
      anaesthetic, a management plan beforehand should include ready availability of
      appropriate drugs and the use of sympathomimetic drugs that are less likely to
      exacerbate the situation.

PMID- 1389855
TI  - Alcohol withdrawal treatment with clonidine.

PMID- 1389856
TI  - Propofol in uraemic patients.

PMID- 1389857
TI  - Bleeding time.

PMID- 1389858
TI  - Bleeding time.

PMID- 1389859
TI  - Bleeding time.

PMID- 1389860
TI  - Training in fibreoptic intubation.

PMID- 1389861
TI  - Blood loss during total hip replacement.

PMID- 1389862
TI  - Venous sequelae of diclofenac.

PMID- 1389863
TI  - Tissue viability. Still arguing over Eusol.

PMID- 1389864
TI  - Pressure area care: monitoring standards.
AB  - This article reviews the establishment of a Pressure Area Care Project Team in
      Gloucester Health Authority, with the aim of shifting the emphasis for care from
      treatment to prevention. A review of literature relating to the causes of
      pressure sores is followed by a description of the group's development of a
      research-based, written policy for prevention.

PMID- 1389866
TI  - HIV and street youth.

PMID- 1389867
TI  - Street youth and AIDS.
AB  - An attempt is made to characterize the population of homeless street youth who
      are living marginally and to describe aspects of this population's dynamics,
      motivations, values, and aspirations. Street youth, ranging in age from birth to
      21, are on the street for one reason or another--dire poverty in the home, which
      necessitates their working on the street to supplement the family income, because
      they have been rejected by parents or guardians, because they have left home due
      to violence in the home, drug or alcohol use by family members, or because of
      lack of a place where they feel they can be "themselves." These conditions make
      street youths particularly vulnerable to HIV infection, not to mention
      malnutrition, stress, and drug use. Their violently accelerated emotional
      maturation, ignorance, alcohol- and drug-induced confusion, together with the
      exploitation and sexual abuse of which they are often victims, are additional
      factors that contribute to sexual practices that may lead to HIV infection.

PMID- 1389865
TI  - Street youth and the AIDS pandemic.
AB  - Children responsible for their own survival exist in all countries. Despite
      social and cultural differences between street youth in developing countries
      versus homeless youth in developed countries, the predictors and correlates of
      homelessness are similar among youth. The AIDS pandemic is inextricably linked to
      homelessness and is a particularly devastating threat to the welfare of the
      world's disenfranchised youth, as they are continually forced into multiple HIV
      related high risk situations and behaviors. Specific recommendations regarding
      clinical care, prevention programs, research, and the implications for policy and
      legislative action are discussed in relation to reducing the incidences and
      impact of HIV. For the world's populations of street children the issue of
      globally providing AIDS education and prevention within the context of health
      care services is emphasized, particularly by the promotion and training of
      physicians and other health professionals in street-based care.

PMID- 1389868
TI  - High-risk behaviors among male street youth in Hollywood, California.
AB  - High-risk sex and drug use behaviors are examined among 446 male street youth 14
      to 23 years old in Hollywood, California (the area in Los Angeles County with the
      highest number of AIDS cases). Comparisons are made based on whether the sex
      behaviors occurred in situations of "survival sex" ("sex you gotta do") and
      "recreational sex" ("sex you wanna do"). Ninety-seven percent of the males were
      sexually active, with 27.1% involved in prostitution in the last 3 months.
      Involvement in prostitution is most common among older, gay identified males. The
      most prevalent risk factors seen among this group include inconsistent condom use
      (which also varies by social situation), high-risk sexual behaviors during both
      survival and recreational sex, large numbers of sexual partners, intravenous drug
      use, and the use of drugs and alcohol during all sex.

PMID- 1389869
TI  - Lifetime sexual behaviors among predominantly minority male runaways and
      gay/bisexual adolescents in New York City.
AB  - Lifetime sexual behaviors were examined among two samples of predominantly
      minority, male adolescents in New York City aged 12 to 18 (M = 16.3), believed to
      be at high risk for HIV infection: 59 runaway males in two residential shelters
      and 60 males attending a community agency (HMI) for gay and bisexual youths.
      Interviews regarding psychosexual milestones indicated that 93% of these youths
      had engaged in oral, anal or vaginal intercourse and/or anilingus, with a median
      of 11.0 female partners among runaway males and a median of 7.0 male partners
      among HMI males. Both groups initiated sexual activity at a relatively early mean
      age of 12.6 years. Each group reported a unique developmental sequence of
      psychosexual milestones. Consistent condom use was reported by 13% of the youths.
      One quarter of the youths reported involvement in prostitution. These findings
      detail the need for AIDS prevention programs for these youths.

PMID- 1389871
TI  - Assistance to AIDS orphans within the family/kinship system and local
      institutions: a program for East Africa.
AB  - The rapid spread of HIV/AIDS infection in East Africa is devastating the adult
      population, leaving behind orphans in need of care. By 2015, there will be an
      estimated 16 million children orphaned by AIDS in Africa alone (Valeroy, 1991).
      Long-term and cost effective programs must be designed that will utilize
      available resources. AIDS orphans have traditionally been relocated within the
      extended family network, although this system is becoming overwhelmed by the
      large numbers of children needing care. In the present paper a family/kinship
      project to support and enhance existing traditional systems and thus ensure
      stable and long-term orphan care is outlined.

PMID- 1389870
TI  - Learning from Norwegian experience: attempts to mobilize the youth culture to
      fight the AIDS epidemic.
AB  - This study describes to what extent Norwegian adolescents were aware of a
      campaign to combat the spread of AIDS, and their participation in the various
      components. The material comprised a nationwide representative sample of 3000
      adolescents aged 17 through 19 years. Data were collected by means of self
      administered, anonymous questionnaires. The response rate was 62.8%. The
      intention of the campaign was to mobilize the youth culture in the fight against
      AIDS with a view to internalizing existing knowledge about HIV and AIDS in the
      hope of improving consistency between knowledge and sexual behavior. The campaign
      included five elements connected to the use of media and activities in the
      adolescents' social environment. The campaign slogan--Talk about sex, about being
      in love and about love--was referred to AIDS only indirectly. The medium used to
      communicate the message was rock music. Over one quarter of the adolescents
      reported a general awareness of the campaign. Awareness of the different elements
      varied between 2.4% and 24.0%. Use of condoms was apparently no higher among
      adolescents who were generally aware of the campaign than among adolescents with
      no knowledge of it. The adolescents had not grasped any specific message from the
      campaign. The campaign would probably have been more successful if the message
      had been more direct and more specific to the context.

PMID- 1389872
TI  - Tracking high-risk adolescents longitudinally.
AB  - Longitudinal tracking methods rarely have been documented. A discussion is
      provided here of tracking methods and strategies used in assessing the
      effectiveness of an AIDS prevention intervention with high-risk adolescents over
      four years. We demonstrated an ability to follow 92% of a sample of unstable
      youths in a difficult urban environment. Successful recontacting of youths
      depended on the structure of the project in the recruitment phases, strategic
      choice of interviewers, a cost-effective payment schedule and other motivators,
      knowledge of appropriate social service agencies that could provide information
      on youths, and methods to elicit cooperation. Confidentiality and other ethical
      issues are discussed.

PMID- 1389873
TI  - Providing AIDS related services to recently arrived immigrant and refugee youth.

PMID- 1389874
TI  - HIV seroprevalence among street involved Canadians in Vancouver.

PMID- 1389875
TI  - The situation in Czechoslovakia.

PMID- 1389876
TI  - The Pan American Health Organization: disadvantaged children and youth STD/HIV
      prevention program.

PMID- 1389877
TI  - Street Kids International: Karate Kids--reaching the unreached.

PMID- 1389878
TI  - Parents and AIDS education.
AB  - The objective of this research was to study parents' attitudes toward AIDS
      education in schools. Questionnaires were mailed to employees in an industrial
      plant and a hospital in a city of 150,000 in Ontario, Canada. Two hundred and
      sixteen questionnaires from parents with children in schools were analyzed. Two
      thirds of the parents agreed that AIDS education should discourage premarital
      sex; whereas, 88% believed that AIDS education should teach about condoms.
      Pearson correlations and multiple regression were used to analyze hypotheses that
      tested attitudes toward AIDS education in the schools. Two predictor variables-
      attitude toward premarital intercourse and fear of casual contact of AIDS--were
      significantly correlated with all three measures of attitudes toward AIDS
      education in the schools. Church attendance and knowledge of AIDS were related to
      both attitudes toward discouraging premarital sex and teaching about condoms.
      Three multiple regression models were constructed to predict attitudes toward
      AIDS education in the schools. The final models accounted for between 11% and 33%
      of the variance.

PMID- 1389879
TI  - The impact of HIV antibody status on gay men's partner preferences: a community
      perspective.
AB  - As more gay men are tested for antibodies to human immunodeficiency virus (HIV),
      serostatus may influence the formation of primary partner bonds in this
      community. We compared seropositive (n = 157), seronegative men (n = 205), and
      those who had not been tested (n = 158) from our ongoing AIDS Behavioral Research
      Project (total response in 1988 = 540). Subjects responded to mailed surveys
      regarding sexual behavior, relationship status, HIV antibody testing and
      serostatus preference when forming relationships for romance and friendship.
      Sixty-eight percent of seropositive gay male respondents reported no serostatus
      preference in partners for romance, while 83% of seronegative respondents and 74%
      of untested respondents preferred seronegative partners for romance. In addition,
      15% of seronegative respondents and 12% of untested respondents preferred
      seronegative individuals for friendship. Seropositive individuals were much less
      likely to be desired for romance or friendship by seronegatives and those who
      have not been tested--at a time when emotional support and companionship are
      obviously needed.

PMID- 1389880
TI  - Joining the front line against HIV: an education program for adult probationers.
AB  - This article describes the implementation and evaluation of a human
      immunodeficiency virus (HIV) education program for adult offenders. Samples of
      Cook County (Chicago) probationers were educated about either HIV or heart
      disease in small group and in one-on-one sessions. The evaluation employed a 2 x
      2 factorial design. Data were collected at 3 points in time: during a pretest,
      posttest, and follow-up. Results showed that offenders' knowledge of HIV was
      increased significantly at posttest and follow-up. Although the HIV presentation
      increased knowledge significantly, it had little impact on HIV-related behavioral
      intentions at posttest or on actual prevention behaviors at follow-up. The
      implications of these findings are discussed with respect to HIV education
      programs in criminal justice settings.

PMID- 1389881
TI  - The link between sexually transmitted disease clinics and HIV counseling and
      testing centers: who is not getting referred?
AB  - A total of 236 clients attending human immunodeficiency virus (HIV) counseling
      and testing (C&T) centers and sexually transmitted disease (STD) clinics were
      interviewed to evaluate who is being reached by C&T services and if STD clients
      are being referred to HIV C&T centers. Respondents receiving HIV C&T reported
      significantly more sexual risk based on characteristics of their partners,
      whereas STD clinics respondents more frequently reported previous STD diagnoses
      and sex with prostitutes. Over 50% of the high-risk individuals attending STD
      clinics were not referred to HIV C&T centers. The differences in perceived risk
      of current and future infection between STD and HIV C&T centers and the low
      referral rates of high-risk individuals for HIV C&T indicate a need for increased
      education efforts, more effective risk-assessment policies in STD clinics, and a
      tightening of the link between STD clinics and HIV C&T centers.

PMID- 1389883
TI  - Preliminary findings from the survey about AIDS for seventh and eighth graders
      (SASEG).
AB  - Four hundred and twelve seventh- and eighth grade students from a predominantly
      white, suburban, middle-class school were surveyed regarding their knowledge and
      attitudes about AIDS. The Survey about AIDS for Seventh and Eighth Graders
      (SASEG) utilized for the study is a 56-item, self-administered questionnaire that
      includes 26 multiple-choice knowledge items, 20 Likert-type attitude items, and
      10 demographic/experiential items. Overall, students were judged to possess
      reasonably high knowledge levels and generally favorable attitudes regarding
      AIDS. However, there were several areas of misinformation and unfavorable
      attitudinal responses. A low positive relationship was found between knowledge
      and attitudes. Higher levels of knowledge and more favorable attitudes were
      associated with being female, being older, and having discussed AIDS with one's
      parents. Higher levels of knowledge were also associated with having had previous
      AIDS instruction and with not knowing someone with AIDS. These findings support
      the need for AIDS education in the pre-high school setting.

PMID- 1389882
TI  - Young children's awareness, knowledge, and beliefs about AIDS: observations from
      a pretest.
AB  - Starting from the assumption that AIDS education can be most effective when
      initiated prior to the age when AIDS risk behaviors emerge, a number of
      researchers and public health officials have advocated AIDS education for
      preadolescents. Yet there have been few published reports assessing children's
      awareness, knowledge, and attitudes about AIDS and persons with AIDS. In this
      paper, basic data are presented for each of these dimensions broken down by race,
      gender, and grade. The data suggest that, although many students are aware of
      AIDS by the first grade, it is not until the fifth grade that nearly all students
      are aware of the existence of the disease. Over all, nearly 44% of the students
      who know about the disease believe that they or someone they know will get it.
      Students in the fifth grade have a higher level of AIDS knowledge than those in
      the first grade, but even the former are relatively uniformed and have a number
      of misconceptions about the disease and persons with it. Children's attitudes
      reflect confusion and some anxiety over AIDS and the treatment of persons with
      it. Some significant race and gender differentials are noted.

PMID- 1389884
TI  - AIDS knowledge in three sites in Bas-Zaire.
AB  - This study surveyed 5,494 women in one urban and two rural sites of Bas-Zaire on
      their knowledge, attitudes, and practices regarding AIDS. The AIDS Risk Reduction
      Model (ARRM) was used to analyze the results to better understand factors that
      may be related to motivation for behavior change. The results show that there are
      considerable barriers to achieving the first stage of the 3-stage model. Most
      notably, only a third of the women believed they were at risk of getting AIDS.
      Those aged 25-29, educated, and married felt themselves to be most at risk.
      Results are compared to other knowledge, attitudes, and practices studies
      conducted in Zaire. Policy implications of these results are discussed.

PMID- 1389885
TI  - HIV/AIDS education and prevention among African-Americans: a focus on culture.
AB  - African-Americans have emerged as the "second wave" of the AIDS epidemic.
      Epidemiologic evidence indicates that African-Americans adults as well as
      adolescents have a disproportionately higher risk of AIDS and human
      immunodeficiency virus (HIV) infection. While programs designed to increase self
      protective behaviors are urgently needed to avert a further increase in HIV
      infection among this population, there is little understanding of African
      American sociocultural factors that may influence the acceptance of HIV
      information and the adoption of HIV-preventive behaviors. This paper describes
      African-American cultural values and mores which may be related to risk-taking
      behavior. Barriers to the effective dissemination of HIV prevention education are
      identified and strategies that may be effective in surmounting these barriers and
      implementing culturally-appropriate HIV behavioral modification programs are
      described.

PMID- 1389886
TI  - 3D acquisition and reconstruction in positron emission tomography.
AB  - 3D positron emission tomography (PET) refers to an acquisition geometry and
      reconstruction procedure that allows all coincidence events within the solid
      angle of the tomograph to be recorded and subsequently reconstructed. The
      reconstruction algorithm must consider the angle of each coincidence event
      relative to the central axis of the scanner. The aim of the technique is to
      maximise the sensitivity of the system by utilising all events that it is
      possible to record from the object. Conventional cylindrical 2D PET systems
      typically detect approximately 0.4%-0.5% of decaying nuclei within the field of
      view; with a 3D system this can increase to over 3%. Reconstruction in 3D using
      filtered-backprojection techniques has been developed and provides results that
      show little degradation of physical characteristics compared with 2D systems,
      apart from an increased scatter event rate. 3D techniques may be used to (i)
      improve data quality using currently acceptable doses of radioactivity and
      scanning times; (ii) extend the scanning period for short-lived tracers,
      especially 11C-labeled ligands; or, conversely (iii) decrease injected doses of
      radiotracer or reduce scanning times to achieve similar results as those using
      current methods in 2D.

PMID- 1389887
TI  - The role of nuclear medicine in oncology.
AB  - Nuclear Medicine offers screening methods for oncology such as bone and bone
      marrow scintigraphy. During the last two decades, special procedures have gained
      widespread application. This paper is centered around the "tumor-specific"
      radiopharmaceuticals. In patients with thyroid cancer, I-131 still plays a
      significant role. Ga-67 still has its indications in lymphoma, while in other
      diseases Tl-201 chloride is now the agent of choice. Especially in thyroid
      cancer, Tl-201 has proved to be a reliable tumor imaging radiopharmaceutical.
      More recently, Tc-99m MIBI was introduced for tumor imaging. Tc-99m HMPAO may
      also be used for tumor scintigraphy, especially in brain lesions. In addition, I
      123 IMP has successfully been used for imaging malignant melanoma. Another
      promising field of tumor diagnosis is receptor imaging. In neuroblastoma and
      malignant pheochromocytoma, I-131/123 mIBG is the radiopharmaceutical of choice
      and may be considered as a receptor imaging agent also. First clinical results
      with In-111 octreotide show potentials as somatostatin-receptor
      radiopharmaceutical in insulinoma, islet cell carcinoma, medullary and lung
      cancer, while I-123 estradiol needs some improvement until it may be recommended
      as diagnostic tool in breast cancer. Since 1978, radiolabeled poly- or monoclonal
      tumor antibodies and their fragments have gained widespread application.
      Especially the Tc-99m 225.28S melanoma antibody, I-131 or Tc-99m CEA and In-111/I
      131 labeled OC-125 antibodies have proven to be of clinical significance in
      melanoma, colorectal and ovarian cancer.

PMID- 1389888
TI  - Re-appraisal of clinical usefulness of 67Ga-citrate scintigraphy for primary
      colorectal carcinoma: with evaluation of scintigram obtained from resected
      specimens.
AB  - Clinical usefulness of 67Ga-citrate scintigraphy for the diagnosis of colorectal
      carcinoma was reappraised at the standpoint of clinicopathological diagnosis.
      Fifty-eight patients with colonic carcinoma were subjected to this study. They
      underwent 67Ga scintigraphy before surgery. Colorectal carcinomas were detected
      in 38 patients, 65.5% by this procedure. Surgical specimens from thirty-seven
      patients underwent postoperative scanning. The scanning of the surgical specimen
      revealed accumulation of 67Ga-citrate in all 37 patients, suggesting that 67Ga
      citrate accumulated in the carcinoma of the colon. The results suggested that
      detectability of carcinoma of the colon by 67Ga scintigraphy in this series was
      better than generally considered. 67Ga scintigraphy was considered to provide
      useful information in cases of severe stenosis and dolichocolon which were
      difficult to diagnose with a Barium enema and fiberscope. The problem is that
      abnormal accumulation is sometimes hard to distinguish from physiological
      excretion in the stools. However we believe that images should be carefully
      evaluated, keeping in mind the fact that 67Ga-citrate could accumulate in a
      colorectal carcinoma, and also believe that we radiologists should actively
      promote Ba-enema examination in positive cases rather than to devote time to the
      differentiation between physiological excretion of 67Ga in the stools and
      accumulation in a colorectal carcinoma.

PMID- 1389889
TI  - Prolonged lung retention of 123I-IMP in pulmonary fibrosis.
AB  - We compared radiographic findings and the retention of N-isopropyl- p[123I]
      iodoamphetamine (123I-IMP) in 23 patients with pulmonary fibrosis. During the 30
      minutes following a rapid injection of 55.5 MBq of 123I-IMP into the antecubital
      vein, the image of regional activity was stored. After this, 185 MBq of 99mTc-MAA
      was injected and its image was stored to determine the region of interest. The
      half time (T1/2) of 123I-IMP release from the lung was calculated in each pixel
      between 10 and 25 minutes after the injection. Chest roentgenograms were taken,
      and the lung field was divided into 6 portions (right upper, middle and lower,
      and left upper, middle and lower). A quantitative score was assigned to the
      radiographic finding (X-ray score). The T1/2 values in the above patients were
      longer than the T1/2 values in normal subjects. Prolonged T1/2 values were
      observed in the lung fields which had high X-ray scores. The X-ray scores and the
      T1/2 values in corresponding areas had a positive relation.

PMID- 1389890
TI  - Correction of scattered photons in Tc-99m imaging by means of a photopeak dual
      energy window acquisition.
AB  - We are proposing a new method for correcting of scattered photons in technetium
      99m (99mTc) imaging by means of photopeak dual-energy window acquisition. This
      method consists of the simultaneous acquisition of two images and estimation of a
      scatter image included in the symmetric energy window (SW) image by the
      difference between these images. The scatter corrected image is obtained by
      subtracting the scatter image from the SW image. In order to evaluate this
      method, we imaged a planar and a SPECT phantom with cold lesions and calculated
      the contrast value with and without the scatter correction. In addition, we
      performed asymmetric energy window (ASW) imaging to compare with this scatter
      correction method for planar images. In the planar image with the tissue
      equivalent material of 10 cm, the scatter correction method removed 32% of the
      counting rate of the SW image and improved from 0.81 to 0.94 of the contrast
      value for a 4 cm-diameter cold lesion, while the contrast value with the ASW was
      0.87 for such a cold lesion. The scatter corrected SPECT image had a reduction of
      18% of the counting rate of the SW SPECT image and improvement of approximately
      11% in contrast for cold spot sizes larger than a 3 cm-diameter, compared with
      the SW SPECT image. In addition, a perfusion defect could be well visualized by
      this scatter correction method on 99mTc-HMPAO regional cerebral blood flow SPECT
      of a patient. Our proposed scatter correction method can improve both planar and
      SPECT images qualitatively and quantitatively.

PMID- 1389891
TI  - In vitro and in vivo characterizations of established human follicular carcinoma
      cell line derived from thyroid cancer: a novel model for well-differentiated
      thyroid malignant tumor.
AB  - A continuous cell line, named SMC R86 F1, was established from a surgically
      resected primary thyroid lesion. The cell grew as an adhering monolayer with a
      doubling time of about 25 hours in modified Eagle's medium supplemented with
      fetal bovine serum. When the cells were transplanted into athymic nude mice,
      tumors developed at the site of inoculation. The cells not only showed epithelial
      origin upon light and electron microscopic examination but also possessed a
      biosynthetic marker human thyroglobulin (hTg). In order to examine the iodide
      trapping ability of the xenografts, radioiodine at doses of 3.7 MBq was injected
      into the peritoneum of 131I treated nude mice bearing xenografts at about 4 weeks
      after the cell inoculation. Judging from the results of scintigraphic,
      autoradiographic and biodistribution studies, viable tissue of the xenografts in
      the treated mice had the ability to trap radioiodine. Histological sections of
      the xenografts resected from the treated mice consisted of follicle-like and
      trabecular growing structures, and immunohistochemically the cytoplasm of the
      tissues was hTg positive. The cells possessed the ability to trap radioactive
      iodine in vitro under the control of TSH. In addition, the expression of
      iodinated 19S Tg in the cell cytoplasms in the monolayer cultures was revealed by
      immunoblotting and autoradiographic assays. These observations provide strong
      evidence that the SMC R86 F1 cell line possesses well-differentiated properties
      of the malignant thyroid follicular epithelial cells.

PMID- 1389892
TI  - An artificial amino acid radiopharmaceutical for single photon emission computed
      tomographic study of pancreatic amino acid transports 123I-3-iodo-alpha-methyl-L
      tyrosine.
AB  - 123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) was selected and its
      characteristics on pancreas accumulation, metabolic selectivity and metabolic
      stability of 125I-L-AMT were studied. The studies on rat tissue slice as well as
      mouse biodistribution proved very high accumulation of 125I-labeled L-AMT in the
      pancreas, which was remarkably inhibited by the active transport inhibitor,
      ouabain. 125I-L-AMT does not enter into protein synthesis and general amino acid
      catabolism. Moreover, 125I-L-AMT was very stable against enzymatic deiodination.
      Thus, the above studies indicated that the 123I-labeled L-AMT was an "artificial
      amino acid" radiopharmaceutical to be used for the selective measurement of the
      membrane amino acid transport rate in the pancreas.

PMID- 1389893
TI  - In vivo distribution of Tc-99m labeled recombinant tissue-type plasminogen
      activator in control and thrombus-bearing rats.
AB  - In vivo distribution of Tc-99m labeled recombinant tissue-type plasminogen
      activator (Tc-99m-rt-PA) was studied in control rats and thrombus-bearing rats.
      To compare fibrin binding in vivo with that in vitro, Tc-99m-rt-PA binding to
      fibrin gel in vitro was also imaged. Rapid blood clearance and accumulation into
      the liver and kidneys were observed in both control and thrombus-bearing rats.
      Accumulation in the stomach, which indicates instability of labeled rt-PA in
      vivo, was very low until two hours after injection. Tc-99m-rt-PA accumulation in
      the clots was higher than that in skeletal and heart muscles, although it was
      lower than in blood, liver, and kidneys. Administration of aprotinin, an
      antifibrinolytic agent, significantly prolonged clot accumulation of Tc-99m-rt-PA
      at 30 minutes after injection. These results suggest that fibrinolysis is
      responsible for the low rt-PA concentration in the clots. A scintigram of a
      thrombus-bearing rat demonstrated increased radioactivity at the clot forming
      site. On the other hand, Tc-99m-labeled human albumin, which was used as a
      control, was not accumulated in the clot. Tc-99m-rt-PA binding to fibrin gel in
      vitro was clearly imaged. By comparison, in vivo fibrin binding of Tc-99m-rt-PA
      was much lower than in vitro. The reasons for low thrombus uptake in vivo may be:
      1. biochemical inactivation of extrinsically administered rt-PA by t-PA
      inhibitor. 2. fibrinolysis by rt-PA activated plasminogen. Overcoming these
      limitations will enable Tc-99m-rt-PA to reach the stage of clinical trials.

PMID- 1389894
TI  - Localization of hyperfunctioning parathyroid glands by means of thallium-201 and
      iodine-131 subtraction scintigraphy in patients with primary and secondary
      hyperparathyroidism.
AB  - The accuracy of the preoperative localization of hyperfunctioning parathyroid
      glands by subtraction scintigraphy with 201Tl and 131I was evaluated by
      comparison with the operative findings. The subjects were 67 consecutive patients
      with hyperparathyroidism (HPT), including 24 with primary and 43 with secondary
      HPT. In primary HPT, surgery revealed 26 adenomas weighing 0.26-15.80 g (mean +/-
      SD; 3.01 +/- 3.04 g). Two patients had double adenomas. Scintigraphy correctly
      localized 25/26 adenomas (96.2%) in primary HPT for a sensitivity, specificity,
      and accuracy of 96.2%, 98.5%, and 97.9%, respectively. In secondary HPT, 163
      hyperplastic glands weighing 0.03-5.08 g (0.85 +/- 0.93 g) were found.
      Scintigraphy correctly localized 79 glands (48.5%) weighing 0.03-5.08 g (1.19 +/-
      1.10 g), but 84 glands (51.5%) weighing 0.04-2.70 g (0.51 +/- 0.50 g) were not
      detected. Thus, the sensitivity, specificity, and accuracy of scintigraphy were
      respectively 48.5%, 100%, and 51.2%, in secondary HPT. These results show that
      scintigraphy with 201Tl and 131I can be used to locate abnormal parathyroid
      glands with an efficacy equal to or better than that of the conventional methods
      with 201Tl and 99mTc or 201Tl and 123I.

PMID- 1389895
TI  - Visualization of bladder diverticulum during Tc-99m DTPA renal scintigraphy.
AB  - An eight-year-old boy with recurrent urinary infection underwent Tc-99m DTPA
      renal scintigraphy for the evaluation of renal function. Stasis of the tracer was
      observed in the pelvocalyceal systems of both kidneys. Intravenous diuretic was
      administered to evaluate a possible mechanical obstruction. During the course of
      the study, a well-defined, round area of activity extended from the bladder which
      was subsequently confirmed to be a diverticulum on voiding cystourethrogram and
      at surgery.

PMID- 1389896
TI  - The value of 99mTc-DTPA renal scintigraphy in the evaluation of post-traumatic
      abdominal fluid collection.
AB  - A patient with a post-traumatic retroperitoneal urinoma is presented. On
      admission, there was a clinical suspicion of retroperitoneal hematoma and
      ultrasonography (US) was performed which showed a hypoechoic fluid collection
      suggesting retroperitoneal hematoma. In order to determine the nature of the
      fluid, radionuclide angiography and renal scan were performed successively with
      99mTc-DTPA. Demonstration of urinary leakage into the mass in the delayed renal
      scintigraphic images suggested a urinoma. At laparotomy, total transection of the
      left ureter in the uretero-pelvic region was found and the diagnosis of urinoma
      was confirmed.

PMID- 1389898
TI  - Functional and morphologic characterization of human T lymphocytes expressing the
      TCR gamma/delta.
AB  - A minor subset of T lymphocytes express a TCR composed of gamma and delta chains.
      This subset differs from conventional T cells for a number of phenotypic and
      functional characteristics. TCR gamma/delta+ cells simultaneously lack both CD4
      and CD8 antigens. Cloning of CD4-8- peripheral blood lymphocytes, under limiting
      dilution conditions, revealed that they are homogeneously composed of cytolytic
      cells which efficiently lyse tumor target cells. Formal proofs have been provided
      that TCR gamma/delta+ cells are able to recognize antigens. For example, they
      proliferated in response to allogeneic mixed lymphocyte culture (MLC); in
      addition, MLC-derived TCR gamma/delta+ cells specifically lysed PHA-induced blast
      cells bearing the stimulating alloantigens. The selection of monoclonal
      antibodies specific for TCR gamma/delta molecules allowed to identify two
      distinct subsets of TCR gamma/delta+ cells. Both of these mABs, termed BB3 and
      delta TCS-1 respectively, induced specific activation of cloned cells expressing
      the corresponding antigenic determinants (as assessed by measurements of
      intracellular Ca++ and/or lymphokine production or cytolytic activity). Analysis
      of the distribution of subsets expressing different forms of TCR gamma/delta,
      showed that the BB3-reactive form is prevalent in the peripheral blood. In
      contrast, delta-TCS-1-reactive cells are relatively infrequent in peripheral
      blood but represent the majority of TCR gamma/delta+ cells in tissues.

PMID- 1389897
TI  - Demonstration of inguinal hernia by means of peritoneal 99mTc-MAA scintigraphy
      with a load produced by standing in a patient treated by continuous ambulatory
      peritoneal dialysis.
AB  - A 45-year-old man receiving continuous ambulatory peritoneal dialysis developed
      scrotal swelling and edema which was aggravated in the standing position.
      Physical examination failed to find inguinal hernia and although ultrasonography
      revealed the patent had processus vaginalias, it failed to prove its continuity
      to the peritesticular space of the tunica vaginalis. Peritoneal scintigraphy with
      intraperitoneal instillation of 99mTc-Macroaggregated albumin followed by
      standing clearly demonstrated the connection. The use of the standing load makes
      possible faster visualization of a positive finding and more accurate diagnosis
      than examination in the supine position.

PMID- 1389899
TI  - Studies on NK cell purification by negative selection in human peripheral blood.
AB  - We have attempted to improve negative selection procedures for the large scale
      purification of human CD-3 CD56+ NK cells. In a series of experiments,
      purifications of NK cells from 10(8) PBMC were performed by T cell depletion
      using either direct or indirect anti-CD3 labeling and the Magnetic Activated Cell
      Separation (MACS) procedure. Contaminating CD3+ cells were still present using
      either one of these two different T cell depletion protocols as shown by
      phenotyping IL-2 supplemented cell cultures on day 12. A second cycle of
      purification was therefore added. When MACS and Dynabeads were compared as
      complementary procedures to the first MACS cycle starting with 10(8) cells, the
      Dynabeads method was found to be superior to the MACS with regard to the
      elimination of residual T cells. Starting from 10(9) PBMC, we showed that this
      MACS+Dynabeads procedure gave similar satisfactory results when compared to the
      scaling-up of a previously established two steps procedure using Dynabeads. These
      two approaches (MACS+Dynabeads and 2 cycles of Dynabeads) have been also tested
      in a clinical setting to purify NK cells from cancer patients prior to in vitro
      expansion. The results indicate that the two methods are equivalent with respect
      to purity and recovery rate; a slight advantage in terms of feasibility was found
      in favor of 2 cycles of Dynabeads.

PMID- 1389900
TI  - Therapeutic and life-prolonging effect of intrapleural injection with a
      streptococcal preparation, OK-432, and IL2-cultured effusion lymphocytes to
      breast cancer patients with malignant pleural effusion.
AB  - We developed a local AIT using PEL cultured with TCGF combined with
      preadministration of OK-432. Twenty-six patients of breast cancer with pleural
      effusion have been treated with this therapy since 1983. PEL expanded and tumor
      cells collapsed by day 9 in culture with TCGF. Cultured PEL possessed
      significantly higher cytotoxic activity against autologous tumor cells than PBL
      cultured in the same condition (p less than 0.05), but there was no difference
      between their cytotoxic activities against K562. The proliferation rate of PEL
      obtained after intrapleural administration of OK-432 was higher than that
      obtained before OK-432 (p less than 0.01). Moreover, the cytotoxic activities
      against both autologous tumor and K562 of cultured PEL obtained after OK-432
      administration was significantly (p less than 0.05) higher than those cultured
      PEL obtained before. Cultured PEL (1 x 10(8)-6 x 10(9)) were transferred into the
      pleural cavity after the intrapleural administration of OK-432 (1-5 KE). The
      volume of pleural effusion increased temporarily after the administration of OK
      432 but significantly (p less than 0.01) decreased after AIT. Tumor cells
      disappeared cytologically in 22 patients at the last puncture of pleural
      effusion. Pleural effusion disappeared completely in 19 of 26 patients and
      decreased by more than 50% in volume in 6 patients. Performance status improved
      in 22 patients. The response rate for OK-432-combined AIT in the present study
      was 96%. The survival period of the patients treated by OK-432-combined AIT in
      this trial was significantly (p less than 0.002) prolonged compared to that of
      the patients receiving chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389901
TI  - Implications of HIV-specific cytotoxic T lymphocytes in AIDS.
AB  - The immune response to HIV in infected humans leads to the production of HIV
      specific cytotoxic T lymphocytes (CTL) which circulate in high frequencies. The
      presence of these CTL and their eventual protective activities have been studied
      by various laboratories, and correlations have been made with certain
      immunopathological manifestations of HIV infections. It seems probable that HIV
      immune CTL participate in the induction of certain disorders by initiating
      inflammatory reactions in the lungs, central nervous system, and lymph nodes.
      Various virus antigens recognized by HIV-immune CTL on the surface of the
      infected cell have been identified, and the molecular definition of the epitopes
      recognized is well under way. Likewise, numerous HLA transplantation antigens
      that regulate HIV antigen recognition by CTL have been identified. These data are
      discussed in view of the development of an eventual vaccine and of functional
      immunotherapies. They are compared with results obtained in animal experimental
      systems.

PMID- 1389902
TI  - Tumor-infiltrating lymphocytes as antitumor effector cells.

PMID- 1389903
TI  - Effective in vivo induction of lymphokine-activated killer (LAK) cells by
      pretreatment with a streptococcal preparation, OK-432.
AB  - Effects of a streptococcal preparation, OK-432, on precursors of lymphokine
      activated killer (LAK) cells were observed in vivo. Total number of splenocytes
      and the ratio of asGM1+ cells increased gradually after i.v. administration of OK
      432, reaching their peaks at 3 to 4 days. It was found that asGM1+ cells were
      nonadherent and large in size. There were little differences in the ratios of Thy
      1+, Lyt-2+, and L3T4+ cells before and after OK-432 treatment. Mice were injected
      i.p. with recombinant interleukin 2 (rIL-2) at a dose of 5 x 10(4) U per mouse 4
      days after OK-432 administration and LAK activity in their splenocytes was
      examined using natural killer (NK) resistant EL-4 target cells. Splenocytes in
      mice treated with both OK-432 and rIL-2 showed higher LAK activity than those in
      mice treated with rIL-2 alone. In vivo treatment with anti asGM1 antibody prior
      to rIL-2 injection abolished completely such augmentation of LAK activity in OK
      432 treated mice. These results demonstrated that asGM1+ LAK precursor cells
      induced by OK-432 were effectively differentiated into LAK cells by rIL-2.

PMID- 1389904
TI  - Cytolytic T lymphocytes: an overview of their characteristics.
AB  - Cloned T cells have been useful for assessing the lytic potential of distinct T
      cell subsets and for determining the relative contribution of different effector
      mechanism involved in the lytic process. Alloreactive CD8+ murine T cell clones
      and cloned murine CD4+ TH1 and TH2 T cells reactive with nominal antigen
      (ovalbumin) lysed nucleated target cells bearing antigen or coated with anti-CD3
      monoclonal antibody in a short term 51Cr-release assay. These clones were also
      evaluated for their ability to lyse efficiently sheep erythrocyte (SRBC) target
      cells coated with anti-CD3 mAb by a mechanism (presumably involving membrane
      damage) that does not involve nuclear degradation. Three patterns of lysis were
      observed: CD8+ and some CD4+ TH2 effector cells lysed efficiently nucleated
      target cells and anucleated SRBC coated with anti-CD3 mAb. However, CD4+ TH1 (and
      a few TH2) T cells which lysed nucleated target cells bearing antigen or coated
      with anti-CD3 mAb did not lyse efficiently the SRBC coated with anti-CD3 mAb. One
      CD4 bearing TH2 cell failed to lyse efficiently either nucleated target cells or
      anucleated SRBC coated with anti-CD3 mAb. These results indicate that both TH1
      and TH2 clones have lytic capabilities. Furthermore, they suggest that some but
      not all TH2 murine T cell clones have lytic characteristics similar to those of
      conventional CD8+ CTL. However, it is not certain how these patterns of lysis of
      target cells in vitro relates to the capacity of CTL to lyse such target cells in
      vivo.

PMID- 1389905
TI  - Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by
      treatment with the streptococcal preparation OK432.
AB  - We investigated whether tumor cell lysis by LAK cells was augmented by treatment
      with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by
      their treatment with OK432. In contrast, the susceptibility of OK432-treated
      Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate
      dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III
      cells by treatment with OK432, and moreover the expression of HLA Class I antigen
      and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it
      is suggested that the enhancement of the susceptibility of OK432-treated tumor
      cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA
      Class I antigen expression.

PMID- 1389906
TI  - Antimetabolites.

PMID- 1389907
TI  - New anticancer agents.

PMID- 1389908
TI  - Monoclonal antibody therapy.

PMID- 1389909
TI  - Biological response modifiers.

PMID- 1389910
TI  - Adoptive cellular therapy.

PMID- 1389912
TI  - Differentiating agents in cancer therapy.

PMID- 1389911
TI  - Growth and differentiation control.

PMID- 1389913
TI  - Alkylating agents.

PMID- 1389914
TI  - Leukemias and plasma cell myeloma.

PMID- 1389915
TI  - Lymphomas.

PMID- 1389916
TI  - Head and neck cancer.

PMID- 1389917
TI  - Anthracyclines.

PMID- 1389918
TI  - Upper gastrointestinal tumors.

PMID- 1389920
TI  - Breast cancer.

PMID- 1389919
TI  - Genitourinary cancer.

PMID- 1389921
TI  - Malignant melanoma.
AB  - The incidence of malignant melanoma in some parts of the world continues to
      increase at a surprising rate. The medical profession is increasingly aware of
      the prognostic implications of tumour thickness, site and the potential value of
      early detection. Surgery for thin lesions remains overwhelmingly the most
      valuable therapy, and despite the very considerable endeavours of research groups
      around the world there is little sight of significant progress in increasing the
      survival of patients with more advanced disease. The reports summarised in this
      and previous annuals confirm the very disappointing results of cytotoxic drugs.
      The results referred to in this review establish that modern immunology is
      capable of devising much more specific immunotherapy than was tried in the early
      days of BCG and C. parvum; notwithstanding the considerable morbidity of some
      biological response modifications, it remains to be shown that the response rates
      achieved can provide useful extension of survival.

PMID- 1389922
TI  - Mitomycin C.

PMID- 1389923
TI  - Soft tissue and bone sarcomas.

PMID- 1389924
TI  - Brain tumors.

PMID- 1389926
TI  - Podophyllotoxin derivatives.

PMID- 1389925
TI  - Supportive care.

PMID- 1389927
TI  - Cisplatin.

PMID- 1389928
TI  - Methods in tropical pharmacology.

PMID- 1389930
TI  - The review of medicines in the United Kingdom.

PMID- 1389929
TI  - Pharmacology and parasitology: integrating experimental methods and approaches to
      falciparum malaria.

PMID- 1389931
TI  - Pharmacodynamics of venlafaxine evaluated by EEG brain mapping, psychometry and
      psychophysiology.
AB  - 1. In a double-blind, placebo-controlled study the effects of venlafaxine--a
      novel nontricyclic compound inhibiting neuronal uptake of serotonin,
      noradrenaline and to a lesser extent dopamine--were investigated utilizing EEG
      brain mapping, psychometric and psychophysiological measures. 2. Sixteen healthy
      volunteers (eight males, eight females) aged 21-36 years received randomized and
      at weekly intervals single oral doses of placebo, 12.5 mg, 25 mg and 50 mg
      venlafaxine. EEG recordings, psychometric and psychophysiological tests, and
      evaluation of pulse, blood pressure and side-effects were carried out at 0, 2, 4,
      6, and 8 h. 3. EEG brain mapping demonstrated that venlafaxine exerted a
      significant action on human brain function as compared with placebo at all three
      doses, characterized mostly by attenuation of absolute power, increase of
      relative delta/theta and beta, and decrease of alpha power, as well as by an
      acceleration of the total centroid fronto-temporally and by its slowing centrally
      and parietally. These findings are similar to antidepressants such as imipramine.
      Topographically, drug-induced alterations were most pronounced over both fronto
      temporal and the right temporal to temporo-occipital regions. 4. Psychometric and
      psychophysiological investigations demonstrated significant dose-dependent
      psychotropic properties of the drug. Multivariate statistics exhibited an
      improvement of both the noopsyche (e.g. attention, concentration, attention
      variability, memory, fine motor activity, reaction time performance) and
      thymopsyche (e.g. drive, wakefulness)) but also significant psychophysiological
      activation (e.g. in c.f.f., pupillary and skin conductance measures). 5. Time
      efficiency calculations showed significant central effects from the 2nd hour
      onwards, with increasing differences between placebo and treatment up to the 8th
      hour. Nausea was the most frequent complaint and appeared dose dependent.

PMID- 1389932
TI  - Scintigraphic studies on the corneal residence of a New Ophthalmic Delivery
      System (NODS): rate of clearance of a soluble marker in relation to duration of
      pharmacological action of pilocarpine.
AB  - 1. A gamma scintigraphic study has been carried out on the precorneal residence
      and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System
      (NODS) containing pilocarpine nitrate in 12 healthy volunteers. 2. The NODS was
      radiolabelled with the soluble marker technetium-99m labelled
      diethylenetriaminepentaacetic acid, to mark the release characteristics of
      soluble drugs contained within the matrix. 3. The relationship between the
      precorneal residence time of the marker and the duration of drug effect on
      intraocular pressure and pupil diameter was monitored. Results obtained following
      administration of the NODS were compared with those obtained after administration
      of a 25 microliters drop of a 2% w/v pilocarpine nitrate solution. Each
      formulation was administered to one eye only, the other eye acting as a control.
      4. Dissolution of the radiolabel from the NODS in vivo showed considerable
      intersubject variation with half-times of dissolution ranging from 46 s to 833 s
      (mean +/- s.d. -280 +/- 217 s), the mean (+/- s.d.) half-time of clearance of the
      radiolabel from the NODS and corneal region of interest was 406 +/- 214 s whereas
      the radiolabelled solution had a mean (+/- s.d.) ocular surface residence time of
      2.9 +/- 1.5 s. 5. Pupil diameter and intraocular pressure were measured for 5 h
      post-administration of the NODS and the solution. After both treatments pupil
      diameter was significantly constricted in the test eye when compared with the
      control eye (P less than 0.001; Student's paired t-test). Pupil diameter was
      constricted by 52% after administration of the NODS and by 35% after
      administration of the solution.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389933
TI  - Autoinduction and steady-state pharmacokinetics of carbamazepine and its major
      metabolites.
AB  - 1. The effect of carbamazepine (CBZ) dose change on mean plasma concentrations of
      CBZ, its two metabolites and apparent steady-state clearance was studied in 77
      affectively ill patients receiving CBZ at doses of 100-1200 mg day-1. 2.
      Autoinduction of CBZ metabolism appeared to be complete within 1 week of starting
      CBZ therapy or dose change, and its degree was linearly related to CBZ daily
      dose. 3. Curvilinear plots were obtained for steady-state concentrations of CBZ
      and its -10,11-epoxide metabolite, and for the ratio of CBZ-10,11-epoxide to CBZ
      level, versus daily dose of CBZ. 4. On the contrary, steady-state concentration
      of CBZ-10,11-diol increased proportionately with the dose. This indicates that
      there is no dose dependency in absorption of CBZ, and that dose-dependent
      autoinduction of CBZ metabolism is the main cause of the curvilinear relationship
      between dose and steady-state concentration of CBZ and its intermediary
      metabolite, CBZ-10,11-epoxide.

PMID- 1389934
TI  - The pharmacokinetics and metabolism of oxycodone after intramuscular and oral
      administration to healthy subjects.
AB  - 1. The pharmacokinetics and metabolism of oxycodone were studied in nine healthy
      young volunteers in a cross-over study. Each subject received oxycodone chloride
      once intramuscularly (0.14 mg kg-1) and twice orally (0.28 mg kg-1) at intervals
      of 2 weeks. A double-blind randomized pretreatment with amitriptyline (10-50 mg a
      day) or placebo was given prior to oral oxycodone. 2. The concentrations of
      oxycodone, noroxycodone and oxymorphone in plasma and the 24 h urine recoveries
      of their conjugated and unconjugated forms were measured by gas chromatography.
      3. No differences were found between treatments in mean Cmax and AUC values of
      oxycodone which varied from 34 to 38 ng ml-1 and from 208 to 245 ng ml-1 h,
      respectively. The median tmax of oxycodone was 1 h in all groups. The
      bioavailability of oral relative to i.m. oxycodone was 60%. The mean renal
      clearance of oxycodone was 0.07-0.08 l min-1. The kinetics of oxycodone were
      unaffected by amitriptyline. 4. The mean ratio of the AUC(0.24 h) values of
      unconjugated noroxycodone to oxycodone was 0.45 after i.m. oxycodone and 0.6-0.8
      after oral oxycodone. Plasma oxymorphone concentrations were below the limit of
      the assay. Eight to 14% of the dose of oxycodone was excreted in the urine as
      unconjugated and conjugated oxycodone over 24 h. Oxymorphone was excreted mainly
      as a conjugate whereas noroxycodone was recovered mostly in an unconjugated form.

PMID- 1389935
TI  - Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral
      administration to healthy volunteers.
AB  - 1. The pharmacokinetics and pharmacodynamics of verapamil administered via the
      oral and sublingual routes were compared in a randomised, two-way cross-over
      study involving six healthy male volunteers. 2. Administered sublingually, a
      verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak
      plasma concentration (P less than 0.05), a greater rate of absorption (P less
      than 0.05), and greater bioavailability (P less than 0.05) when compared with
      orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing,
      PR intervals were significantly (P less than 0.05) prolonged between 30 and 90
      min after sublingual verapamil dosing. 4. Correlations between log plasma
      verapamil concentration and percentage increase in PR interval were greater after
      sublingual compared with oral dosing in all volunteers.

PMID- 1389936
TI  - The pharmacokinetics of mecillinam and pivmecillinam in pregnant and non-pregnant
      women.
AB  - 1. The pharmacokinetics of parenteral mecillinam (n = 27) and oral pivmecillinam
      (n = 12) were studied in pregnant (n = 27) and non-pregnant (n = 12) subjects. 2.
      In early pregnancy (9-14 weeks of gestation) the mean peak plasma drug
      concentration (Cmax = 19 +/- 9 micrograms ml-1) after an intravenous injection of
      200 mg mecillinam was significantly lower (P less than 0.05) and the volume of
      distribution (V = 49 +/- 20.1) significantly larger (P less than 0.05) than in
      non-pregnant subjects (Cmax = 35 +/- 18 micrograms ml-1, V = 29 +/- 12.1). In
      late pregnancy (39-40 weeks of gestation) the plasma mean peak concentration
      (Cmax = (29 +/- 14 micrograms ml-1) after parenteral administration of 200 mg
      mecillinam was slightly lower and the volume of distribution (V = 65 +/- 29.1, V
      = 0.9 +/- 0.4 l kg-1) significantly larger than that in non-pregnant subjects (V
      = 0.4 +/- 0.3 l kg-1). Also after oral administration of 200 mg pivmecillinam,
      equimolar to 136.5 mg mecillinam, the mean peak plasma concentration in pregnant
      subjects (Cmax = 1.8 +/- 1.2 micrograms ml-1) was slightly lower than that in non
      pregnant subjects (Cmax = 1.7 +/- 1.2 micrograms ml-1). 3. The mean half-life of
      elimination after parenteral administration of mecillinam was significantly
      longer during both early (t1/2,Z = 133 +/- 38 min, P less than 0.05) and late
      pregnancy (t1/2,Z = 107 +/- 41 min, P less than 0.05) as compared with the non
      pregnant state (t1/2,Z = 75 +/- 21 min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1389938
TI  - The influence of particle size on the bioavailability of inhaled temazepam.
AB  - 1. Temazepam was administered by aerosol using a standard protocol to healthy
      volunteers. Two studies are reported in which different dosage formulations were
      used: a) 30 mg of the 5 mu diameter particle (n = 6); b) 10 mg of the 2 mu
      diameter particle (n = 6). 2. An open crossover design was followed in each
      study. On one occasion in both studies subjects used a gargling procedure to
      remove drug which had been deposited in the mouth and oropharynx. 3. Serial
      venous blood samples were drawn for a period of 24 h. The mean total AUC of the 5
      mu preparation was significantly reduced by gargling (3153 ng ml-1 h to 1066 ng
      ml-1 h) (F = 0.32). Gargling also had a significant effect on the mean AUC(0-1
      h). 4. In contrast gargling had no significant effect on the mean AUC associated
      with the smaller diameter particle preparation (630 ng ml-1 h) vs 397 ng ml-1 h
      (F = 0.74). 5. These findings also indicate that temazepam deposition in the
      pulmonary tree is enhanced by the use of a 2 mu rather than a 5 mu diameter
      particle. However, the plasma drug concentrations achieved are unlikely to
      produce a sufficiently marked sedative effect for endoscopic investigations such
      as gastroscopy.

PMID- 1389937
TI  - The excretion of dothiepin and its primary metabolites in breast milk.
AB  - 1. The excretion of dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S
      oxide into breast milk was studied in eight women. Exposure to drug was measured
      in five of their infants, and possible drug-related effects were assessed in all
      eight infants. 2. Using pre-feed milk samples mean (+/- s.e. mean) milk:plasma
      (M:P) ratios were 0.78 +/- 0.12, 0.85 +/- 0.16, 1.18 +/- 0.29 and 1.86 +/- 0.29
      for dothiepin, nordothiepin, dothiepin-S-oxide and nordothiepin-S-oxide,
      respectively. In post-feed milk samples, the mean M:P ratio for dothiepin (1.59
      +/- 0.32) was significantly greater (P less than 0.05) but M:P ratios for the
      metabolites were similar. 3. Mean total calculated infant daily doses, (in
      dothiepin equivalents and as a percent of the maternal dose) were 0.58% for
      dothiepin, 0.23% for nordothiepin, 2.47% for dothiepin-S-oxide, and 1.17% for
      nordothiepin-S-oxide. 4. Plasma samples were obtained from five infants. In one,
      both dothiepin and nordothiepin were below their minimum quantifiable levels (2
      micrograms l-1) while in four others both dothiepin-S-oxide and nordothiepin-S
      oxide were below their minimum quantifiable levels (10 micrograms l-1). No
      adverse effects were found in any of the eight infants. 5. Use of dothiepin by
      depressed mothers is unlikely to be a significant hazard to their breast-feeding
      infants.

PMID- 1389940
TI  - The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected
      patients.
AB  - Eleven HIV-infected men participated in a randomized, two-treatment, two-period
      crossover study to determine the effect of a 25 g protein meal on zidovudine
      pharmacokinetics. On two separate occasions, 1 week apart, each patient received
      200 mg zidovudine in a fasting state or immediately following the protein meal. A
      protein meal significantly decreased Cmax [532 (228 s.d.) vs 802 (452 s.d.) ng ml
      1, P = 0.004] and increased mean residence time (138 (26 s.d.) vs 114 (26 s.d.)
      min, corrected for lag times, P = 0.001). However, AUC, tmax, terminal half-life
      and renal clearance were not significantly altered (P greater than 0.05). The
      power to detect a 20% change in AUC was 98% at the 5% significance level. In
      contrast to fat-containing foods, protein-based meals may not alter the extent of
      zidovudine absorption.

PMID- 1389939
TI  - Variability of the serum protein binding of theophylline in patients with asthma
      and cystic fibrosis.
AB  - 1. The serum protein binding of theophylline was studied in 28 asthmatics and 11
      patients with cystic fibrosis (CF) who were receiving the drug regularly. Peak
      theophylline samples were collected at 2 week intervals on four occasions in each
      asthmatic and on three occasions in each CF patient. The binding was measured
      using ultrafiltration at 37 degrees C and pH 7.4. The total and free (unbound)
      theophylline concentrations were measured using high-performance liquid
      chromatography. 2. The mean free-fractions (+/- s.d.) in asthmatics (0.50 +/-
      0.03) and in CF patients (0.51 +/- 0.04) were not significantly different. The
      intra- and inter-subject variability in the free-fraction (fu) was relatively
      small in both patient groups. The binding was found to be concentration
      independent at serum theophylline concentrations up to 30.9 micrograms ml-1. The
      effects of age, gender, serum albumin and total serum protein on the free
      fraction were evaluated. 3. The results indicate that the binding of theophylline
      is similar in the two disease states. The low degree of variability in serum
      theophylline binding indicates that measurements of total serum theophylline
      concentrations will reflect unbound serum concentrations with acceptable accuracy
      in both patient groups studied.

PMID- 1389941
TI  - Cyclosporin metabolism by human gastrointestinal mucosal microsomes.
AB  - The in vitro metabolism of the immunosuppressant cyclosporin (CsA) by human
      gastrointestinal mucosal microsomes has been studied. Macroscopically normal
      intestinal (n = 4) and liver (n = 2) tissue was obtained from kidney transplant
      donors, and microsomes prepared. Intestinal metabolism was most extensive with
      duodenal protein (15% conversion to metabolites M1/M17 after 2 h incubation at 37
      degrees C; metabolite measurement by h.p.l.c). Western blotting confirmed the
      presence of P-4503A (enzyme subfamily responsible for CsA metabolism) in duodenum
      and ileum tissue, but not in colon tissue. The results of this study indicate
      that the gut wall may play a role in the first-pass metabolism of CsA, and could
      therefore be a contributory factor to the highly variable oral bioavailability of
      CsA.

PMID- 1389942
TI  - Gerontokinetics--a reply.

PMID- 1389943
TI  - Caution in the use of a 100 mg dose of racemic mephenytoin for phenotyping
      southeastern Oriental subjects.

PMID- 1389945
TI  - Flosequinan does not affect systemic and regional vascular responses to simulated
      orthostatic stress in healthy volunteers.
AB  - 1. The effects of a single oral dose (100 mg) of flosequinan on systemic and
      regional (forearm, splanchnic and renal) vascular responses to simulated
      orthostatic stress (lower body negative pressure, LBNP) were investigated in nine
      healthy male volunteers, in a double-blind, placebo-controlled crossover study.
      2. Forty-five minutes after its administration and before LBNP, flosequinan
      induced a significant decrease in total peripheral and in forearm vascular
      resistances without any concomitant change in arterial pressure, in heart rate
      and in the investigated biological parameters (plasma catecholamines, arginine
      vasopressin and renin activity). 3. After flosequinan and placebo, LBNP induced
      similar decreases in central venous pressure at all levels of LBNP (-10, -20 and 
      40 mm Hg) and in pulse pressure at LBNP -40 mm Hg. LBNP-induced increase in
      forearm vascular resistance was significantly more marked after flosequinan than
      after placebo at all levels of LBNP, and this was also true for splanchnic
      vascular resistance but at LBNP -40 mm Hg only. However, inasmuch as the basal
      values of these two parameters before LBNP were lower after flosequinan than
      after placebo, their final values after LBNP -40 mm Hg were similar. Finally,
      LBNP-induced changes in renal vascular resistance, glomerular filtration rate and
      filtration fraction as well as in plasma catecholamines, arginine vasopressin and
      renin activity were similar after flosequinan and placebo at all levels of LBNP.
      4. Flosequinan affected neither reflex control of heart rate (phenylephrine test)
      nor non-specific vasoconstrictor responses (cold pressor test). (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1389946
TI  - Postmarketing surveillance of captopril for hypertension.
AB  - 1. A scheme for augmented spontaneous reporting of adverse drug events using
      advanced view data systems was developed and applied to study 67,698 consecutive
      patients prescribed captopril in general practice for the treatment of
      hypertension. 2. Captopril was an effective hypotensive agent in this population,
      as only 1.9% of patients were withdrawn because of apparent inefficacy. 3.
      Adverse effects of captopril resulted in withdrawal of treatment in 8.9% of
      recipients, and such effects were more frequent in elderly and female recipients.
      4. Skin reactions--usually maculopapular rashes--tended to occur early during
      therapy whereas cough occurred much later and was reported more frequently in non
      smokers. 5. Some 1.1% of recipients died during follow-up. There was no evidence
      of any unusual or unexpected causes of death which might be partially or totally
      captopril-related in the study cohort. 6. The study confirms the feasibility of
      large scale postmarketing surveillance studied in general practice and allowed
      risk benefit assessments to be made on the use of captopril for treating
      hypertension.

PMID- 1389947
TI  - Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after
      single and repeated oral doses.
AB  - 1. The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10
      alcohol dependent subjects after single and repeated therapeutic oral doses (25
      mg kg-1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly
      eliminated (tmax = 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of
      unchanged GHB was negligible (less than 1% of the dose). gamma-butyrolactone was
      not detected in either plasma or urine, indicating that lactonization of GHB does
      not occur in vivo. 3. The multiple-dose regimen resulted neither in accumulation
      of GHB nor in time-dependent modification of its pharmacokinetics. 4. In five
      subjects, the data were consistent with nonlinear elimination kinetics of GHB.
      Administration of a 50 mg kg-1 dose to these subjects resulted in significant
      increases in dose-normalized AUC, t1/2z and mean residence time. 5. Doubling of
      the dose also resulted in a significant increase in tmax with little change in
      Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and
      caused no serious side effects.

PMID- 1389948
TI  - The use of cimetidine to reduce dapsone-dependent methaemoglobinaemia in
      dermatitis herpetiformis patients.
AB  - 1. We have attempted to reduce dapsone-dependent methaemoglobinaemia formation in
      six dermatitis herpetiformis patients stabilised on dapsone by the co
      administration of cimetidine. 2. In comparison with control, i.e. dapsone alone,
      methaemoglobinaemia due to dapsone fell by 27.3 +/- 6.7% and 26.6 +/- 5.6% the
      first and second weeks after commencement of cimetidine administration. The
      normally cyanotic appearance of the patient on the highest dose of dapsone (350
      mg day-1), underwent marked improvement. 3. There was a significant increase in
      the trough plasma concentration of dapsone (2.8 +/- 0.8 x 10(-5)% dose ml-1) at
      day 21 in the presence of cimetidine compared with control (day 7, 1.9 +/- 0.6 x
      10(-5)% dose ml-1, P less than 0.01). During the period of the study, dapsone
      mediated control of the dermatitis herpetiformis in all six patients was
      unchanged. 4. Trough plasma concentrations of monoacetyl dapsone were
      significantly increased (P less than 0.05) at day 21 (1.9 +/- 1.0 x 10(-5)% dose
      ml-1) compared with day 7 (1.6 +/- 0.9 x 10(-5)% dose ml-1:control). 5. Over a 12
      h period, 20.6 +/- 8.9% (day 0) of a dose of dapsone was detectable in urine as
      dapsone hydroxylamine. Significantly less dapsone hydroxylamine was recovered
      from urine at day 14 (15.0 +/- 8.4) in the presence of cimetidine, compared with
      day 0 (control: P less than 0.05). 6. The co-administration of cimetidine may be
      of value in increasing patient tolerance to dapsone, a widely used, effective,
      but comparatively toxic drug.

PMID- 1389944
TI  - Drug therapy of ulcerative colitis.

PMID- 1389949
TI  - N-demethylation of ethylmorphine in pregnant and non-pregnant women and in men:
      an evaluation of the effects of sex steroids.
AB  - 1. The effects of oestrogens, testosterone, progesterone and medroxyprogesterone
      acetate (MPA) on the rate of N-demethylation of ethylmorphine (EM) to
      norethylmorphine (NEM) were studied in human adult liver microsomes. 2. N
      Demethylase activity was found to be inhibited by progesterone and MPA to a
      similar extent while oestrogens and testosterone had no or negligible effects. 3.
      These findings prompted us to measure the N-demethylation of EM in relation to
      serum progesterone concentration in vivo in three groups of volunteers with large
      physiological differences in their endogenous levels of progesterone, i.e. i)
      pregnant women, ii) non-pregnant ovulating women and iii) men. 4. The metabolic
      ratio (MRP) of EM to NEM in plasma 60 min after dosage and the corresponding
      ratio in urine sampled for 6 h (MRU,1), measured on two occasions 14 days apart
      were used to reflect intraindividual variation in the rate of N-demethylation. 5.
      The average difference in MRP and MRU,1 between the two occasions was similar in
      all groups. However, the variability in MRP between individuals within a group
      was significantly higher in ovulating women than in men, but this had no relation
      to the serum concentrations of progesterone or oestradiol. 6. The cumulative 12 h
      urinary excretion of EM, NEM and morphine (MO) after hydrolysis with beta
      glucuronidase was about 46%. There was no difference in the metabolic ratio of EM
      to NEM and its conjugate(s) in the urine between the luteal and the follicular
      phases. Our findings suggest that the menstrual cycle does not influence the rate
      of N-demethylation of EM.

PMID- 1389950
TI  - Inhibitors of imipramine metabolism by human liver microsomes.
AB  - 1. The aromatic 2-hydroxylation of imipramine was studied in microsomes from
      three human livers. The kinetics were best described by a biphasic enzyme model.
      The estimated values of Vmax and Km for the high affinity site ranged from 3.2 to
      5.7 nmol mg-1 h-1 and from 25 to 31 microM, respectively. 2. Quinidine was a
      potent inhibitor of the high affinity site for the 2-hydroxylation of imipramine
      in microsomes from all three human livers, with apparent Ki-values ranging from 9
      to 92 nM. This finding strongly suggests that the high affinity enzyme is CYP2D6,
      the source of the sparteine/debrisoquine oxidation polymorphism. 3. The selective
      serotonin reuptake inhibitors (SSRI), paroxetine, fluoxetine and norfluoxetine
      were potent inhibitors of the high affinity site having apparent Ki-values of
      0.36, 0.92 and 0.33 microM, respectively. Three other SSRIs, citalopram,
      desmethylcitalopram and fluvoxamine, were less potent inhibitors of CYP2D6, with
      apparent Ki-values of 19, 1.3 and 3.9 microM, respectively. 4. Among 20 drugs
      screened, fluvoxamine was the only potent inhibitor of the N-demethylation of
      imipramine, with a Ki-value of 0.14 microM. 5. Neither mephenytoin, citalopram,
      diazepam, omeprazole or proguanil showed any inhibition of the N-demethylation of
      imipramine and the role of the S-mephenytoin hydroxylase for this oxidative
      pathway could not be confirmed.

PMID- 1389951
TI  - The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6
      (CYP2D6) activity in human liver microsomes.
AB  - Inhibition of human cytochrome P4502D6 (CYP2D6)-catalysed metabolism can lead to
      clinically significant alterations in pharmacokinetics. Since there is evidence
      that the selective serotonin reuptake inhibitor (SSRI) class of antidepressant
      drugs might inhibit CYP2D6, the effects of five SSRIs on human liver microsomal
      CYP2D6 activity were compared with each other and with three tricyclic
      antidepressant drugs. On a molar basis, paroxetine was the most potent of the
      SSRIs at inhibiting the CYP2D6-catalysed oxidation of sparteine (Ki = 0.15
      microM), although fluoxetine (0.60 microM) and sertaline (0.70 microM) had Ki
      values in the same range. Fluvoxamine (8.2 microM) and citalopram (5.1 microM)
      also inhibited CYP2D6 activity. The major circulating metabolites of paroxetine
      in man produced negligible inhibition. In contrast, norfluoxetine the active
      metabolite of fluoxetine, was a potent CYP2D6 inhibitor (0.43 microM). CYP2D6
      activity was also diminished by the tricyclic antidepressant drugs clomipramine
      (2.2 microM), desipramine (2.3 microM) and amitriptyline (4.0 microM). These
      findings suggest that compounds with SSRI activity are likely to interact with
      human CYP2D6 in vivo with the potential of causing drug interactions.

PMID- 1389952
TI  - Ipratropium bromide delivered orally by metered dose inhaler does not decrease
      salivary flow in normal subjects.
AB  - A randomised placebo-controlled cross-over group study was conducted to ascertain
      the occurrence and duration of xerostomia induced by 240 micrograms (high dose)
      and 120 micrograms (low dose) of ipratropium bromide (IPB) delivered by metered
      dose inhaler (MDI) into the mouth in normal subjects. Salivary output was higher
      with both doses of IPB than with placebo though the differences were not
      statistically significant. IPB was less palatable than placebo as indicated on
      visual analogue scale (VAS) and the taste of the drug may have caused a reflex
      increase in salivary output from the major salivary glands which would have
      masked any possible local effect of the drug on the smaller submucosal glands of
      the mouth. IPB delivered into the oral cavity by MDI is therefore not a suitable
      treatment for hypersalivation.

PMID- 1389953
TI  - Ocular hypotensive effects of medifoxamine.
AB  - Medifoxamine is a novel monoamine re-uptake inhibiting antidepressive drug which
      preferentially inhibits dopamine reuptake. In human volunteer studies it has been
      found to reduce significantly intraocular pressure after single oral doses of 300
      1000 mg, and to produce a small but statistically significant miosis. Its maximal
      ocular hypotensive action was less than that of oral timolol 20 mg.

PMID- 1389954
TI  - Diffusion of cloxacillin into synovial tissue.
AB  - After a 30 min i.v. infusion of 1 g cloxacillin, the concentrations of this
      antibiotic were measured in plasma and synovial tissue samples from 11 patients
      undergoing total hip replacement. Assuming passive distribution between plasma
      and tissue the rate constants of distribution were estimated. The mean half-life
      of distribution was 22 min. The concentration of free drug in synovial tissue was
      estimated to be 77% of the total tissue concentration. The maximum tissue drug
      concentration after an i.v. bolus dose is predicted to occur at about 37 min.

PMID- 1389955
TI  - A comparison of gastric emptying rate after cimetidine and ranitidine measured by
      applied potential tomography.
AB  - Gastric emptying was measured using applied potential tomography (APT) after
      crossover administration of 800 mg cimetidine and 300 mg ranitidine orally. Ten
      volunteers were studied, each on two occasions. Two hours after taking ranitidine
      or cimetidine, the volunteer was given a liquid and gastric emptying was measured
      over 60 min. There was a small but statistically significant delay in gastric
      emptying following ranitidine compared with cimetidine (P less than 0.04). The
      median (range) time to 50% emptying (t50) was 24 (15-60) min after ranitidine
      compared with 22 (15-46) min after cimetidine.

PMID- 1389956
TI  - Therapeutic modulation of brain temperature: relevance to ischemic brain injury.
AB  - Hypothermia was first applied therapeutically as a local anesthetic and later was
      used to achieve organ protection during procedures necessitating circulatory
      interruption. Profound whole-body hypothermia, typically carried out in
      conjunction with extracorporeal bypass, has long been employed during cardiac and
      neurosurgical operative procedures. More recently, studies in small-animal
      experimental models of cerebral ischemia have provided persuasive evidence that
      even small decreases in brain temperature confer striking protection against
      ischemic neuronal injury. By contrast, small elevations of brain temperature
      during ischemia accelerate and extend pathologic changes in the brain and promote
      early disruption of the blood-brain barrier. Hypothermia retards the rate of high
      energy phosphate depletion during ischemia and promotes postischemic metabolic
      recovery. More importantly, mild intraischemic hypothermia markedly attenuates
      the release of glutamate into the brain's extracellular space and significantly
      diminishes the release of dopamine. Similarly, the inhibition of calcium
      calmodulin-dependent protein kinase II triggered by normothermic ischemia is
      prevented by hypothermia, as is the ischemia-induced translocation and inhibition
      of the key regulatory enzyme protein kinase C. Hypothermia also appears to
      facilitate the resynthesis of ubiquitin following ischemia. Studies of potential
      clinical importance have shown that moderate hypothermia is capable of
      attenuating ischemic damage even if instituted early in the postischemic period.
      In the setting of focal cerebral ischemia, moderate brain hypothermia reduces the
      infarct size (particularly in the setting of reversible middle cerebral artery
      occlusion); conversely, hyperthermia markedly increases the infarct volume. These
      studies underscore the importance of monitoring and regulating the brain
      temperature during experimental studies of cerebral ischemia to insure a
      consistent pathologic outcome and to avoid the false attribution of
      "pharmacoprotection" to drugs that reduce the body temperature. The measurement
      of brain temperature is now practicable in neurosurgical patients requiring
      invasive monitoring, and human studies have shown that cortical and
      cerebroventricular temperatures may exceed systemic temperatures. Mild to
      moderate decreases in brain temperature are neuroprotective in cerebral ischemia,
      while mild elevations of brain temperature are markedly deleterious in the
      setting of ischemia or injury. It is anticipated that controlled clinical trials
      of therapeutic brain temperature modulation will be undertaken over the next
      several years.

PMID- 1389957
TI  - The blood-brain barrier and cerebral microcirculation in Alzheimer disease.
AB  - Current evidence does not preclude the possibility that breach of the blood-brain
      barrier (BBB) is causally involved in the pathogenesis of Alzheimer disease (AD).
      There is abundant evidence, however, indicating morphological and biochemical
      abnormalities in the cerebral microvasculature that implicate breakdown of the
      BBB in AD. These abnormalities include profound irregularities in the course of
      vessels and the vascular basement membrane, changes in specific proteins and
      receptors associated with the cerebral endothelium, and increases in perivascular
      infiltrates. While noninvasive imaging and permeability studies provide no clear
      functional evidence to support the prevailing morphological evidence, focal and
      transient loss of integrity of the BBB in AD is probable. Thus, neuronal
      populations in circumscribed areas could become vulnerable. Cerebral amyloid
      angiopathy (CAA) is one of the pathological features highly associated with AD
      that may exacerbate the degenerative process. CAA may develop as a consequence of
      vascular changes at predisposed sites and precede at least some of the
      parenchymal amyloid deposits. It is not unlikely that many of these vascular
      changes contribute to the development of chronic hypoperfusion (or
      cerebrovascular insufficiency) that may lead to the progressive decline of
      cerebral functions in concert with aging.

PMID- 1389958
TI  - Capillary circulation in the brain.
AB  - A close relationship exists between the local capillary density in different
      brain structures and their local blood flow and metabolism. Capillary density
      appears to have developed depending on local functional demands. Investigation of
      single capillary perfusion has shown that all capillaries are perfused with
      plasma in the brain at any time point. Theories of capillary cycling and
      capillary recruitment have been based on experimental artifacts. Indirect
      evidence exists for a heterogeneity of perfusion under normal conditions,
      especially with respect to erythrocyte flow. The capillary diffusion capacity
      depends on, among other things, the available capillary surface area, which would
      increase with recruitment of capillaries. In the case of capillary perfusion
      heterogeneity, the capillary diffusion capacity may also be increased by
      homogenization of the perfusion rate (slowly perfused capillaries becoming faster
      perfused). This could give a physiological impression of an "apparent" increase
      in the capillary surface area. It is recommended that the terms "capillary
      cycling" and "recruitment" should be used in conjunction with more specific
      explanations, like "recruitment of erythrocytes" and "recruitment of previously
      nonperfused capillaries".

PMID- 1389959
TI  - Structural characteristics of cyclodextrins in the solid state.
AB  - A comparison of alpha-, beta-, and gamma-cyclodextrins in the solid state is
      made. Monomeric features analyzed include orientations of primary hydroxyl groups
      and pyran ring pucker. Macromolecular features examined include planarity of the
      oligomer, tilting of pyran rings, and, deviation from Cn symmetry where n =
      number of monomers. The mean values and standard deviations of these shape
      descriptors are given for cyclodextrins with and without guests embedded in their
      interiors. Molecular mechanics calculations using the MM2, AMBER, and CHARMM
      force fields show that most solid state cyclodextrins are trapped in high-energy
      conformations relative to the most stable forms found in this study.

PMID- 1389960
TI  - Synthesis and pharmacological investigation of stereoisomeric muscarines.
AB  - The synthesis of the eight stereoisomers of muscarine has been efficiently
      accomplished by utilizing the two enantiomers of lactic esters as starting
      material. The synthetic strategy is based on a SnCl4-catalyzed addition of
      allyltrimethylsilane to O-protected lactic aldehydes followed by an
      iodocyclization process. All the final derivatives possess an enantiomeric excess
      higher than 98%. The four pairs of enantiomers bound to M1, M2, and M3 muscarinic
      receptor subtypes in membranes from cerebral cortex, heart, and salivary glands,
      respectively, and recognized heterogeneous states of the receptors. Of the eight
      isomers, only natural muscarine (+)-1 recognized three affinity states of the M2
      receptor. The compound was also the only one to show selectivity in the binding
      study, demonstrating 37- to 44-fold higher affinity for the M2 than for the M1 or
      M3 receptors. In addition, the compounds were tested in functional assays on
      isolated guinea pig atria (M2 receptors) and ileum (mixed population of M2 and M3
      receptors) and their muscarinic potencies were determined. Among the eight
      isomers, again only (+)-1 enantiomer was found to be very active on both tissues.
      Its potency was more than two orders of magnitude higher than that of its
      enantiomer (-)-1 as well as the other six isomers. The eudismic ratios (E.R.)
      deduced from the two functional tests were 324 and 331.

PMID- 1389961
TI  - Stereoselective binding of etodolac to human serum albumin.
AB  - The protein binding of etodolac enantiomers was studied in vitro by equilibrium
      dialysis in human serum albumin (HSA) of various concentrations varying from 1 to
      40 g/liter, by addition of each enantiomer at increasing concentrations. In the 1
      g/liter solution, at the lowest drug levels, the (R)-form is more bound than its
      antipode, the contrary being observed at the highest drug levels. For higher
      albumin concentrations, S was bound in a larger extent than R. Using the
      displacement of specific markers of HSA sites I and II, studied by
      spectrofluorimetry, it was suggested that R and S are both bound to site I, while
      only S is strongly bound to site II.

PMID- 1389962
TI  - Enzymes in stereoselective pharmacokinetics of endogenous substances.
AB  - The use of enzymes to assay individual components of the L-carnitine family in
      pharmaceuticals, foodstuffs, and biological fluids with various forms of
      detection is reviewed. The most useful enzyme in the assay of compounds of the L
      carnitine family is carnitine acetyl transferase (CAT), which catalyses the
      reversible interconversion of L-carnitine and its short-chain acyl esters. CAT
      can be used in one or more coupled reactions combined with U.V., or radiolabelled
      detection, or combined with HPLC, allowing, enantioselective, structurally
      specific, and, in the case of radiolabelled tracing, highly sensitive assays to
      be carried out. When compared with chromatographic separation of enantiomers or
      diastereoisomers, enantioselective enzyme mediated assays may be cheaper, more
      sensitive, and simpler, but they do not allow the nonpreferred isomer to be
      assayed. Consequently, they are appropriate for the specific assay of endogenous
      enantiomeric substrates of the enzyme concerned, in biological samples. The
      analysis of the other enantiomer in raw materials or in pharmaceuticals must be
      more properly approached by enantioselective chromatographic methods.

PMID- 1389963
TI  - Stereospecific gas chromatographic method for determination of methadone in
      serum.
AB  - rac-Methadone is used clinically for the chronic maintenance treatment of heroin
      addiction and for the relief of pain. As the pharmacological activity of
      methadone is due primarily to the (-)-(R)-enantiomer, stereospecific measurements
      of methadone serum concentrations in methadone-treated patients are expected to
      be more relevant for clinical studies than earlier described total drug
      measurements. This study describes a stereospecific gas chromatographic (GC)
      method for the determination of methadone in serum. The extracted methadone was
      derivatizised with (-)-menthyl chloroformate. The diastereometric derivatives
      were analysed by GC on a capillary column and detected with a nitrogen-phosphorus
      detector. The resolution factor obtained for the methadone enantiomers was 1.1
      with a relatively short time of analysis (30 min). By analysing the pure (-)-(R)
      enantiomer, no racemization was seen during the analysis. The lower limit of
      quantitation was 75 nmol/l for each enantiomer. Measurements of the ratio between
      (-)-(R)- and (+)-(S)-methadone concentrations in serum from five methadone
      treated patients showed interindividual differences (range 0.5-1.1). The patient
      results correlated well with those from another GC method measuring total
      methadone.

PMID- 1389965
TI  - [The publishing syndrome].

PMID- 1389964
TI  - Resolution of terfenadine enantiomers by beta-cyclodextrin chiral stationary
      phase high-performance liquid chromatography.
AB  - Enantiomers of terfenadine were resolved by high-performance liquid
      chromatography (HPLC) using a chiral stationary phase (CSP) column packed with
      beta-cyclodextrin (beta-CD) covalently bound to silica. Separation was achieved
      in both the reverse phase and normal phase modes. Resolution of enantiomers was
      confirmed by ultraviolet-visible absorption, circular dichroism, and mass
      spectral analysis.

PMID- 1389966
TI  - [Characteristics of cicatrization of wounds during the fetal period].
AB  - Recent clinical experience on open prenatal surgery in human beings, although
      scarce, suggests that skin wound healing in the fetus differs from that in adult
      life. This fact is supported by several experimental studies. Three types of skin
      wounds have been practiced in a group of thirty 23rd-gestational-day rabbit
      fetuses: sutured incision, non-sutured incision, and electrocautery burn. Seven
      days later, the resulting scars were assessed by mechanical and hystological
      studies. The results obtained were compared with those seen in 30 newborn rabbits
      and 30 adult rabbits in which the same wounds were carried out. In the fetuses,
      rupture tension of the sutured wound was 20% of that of the normal skin. A
      similar relationship was found in the group of adult rabbits. The sutured wounds
      in the fetuses showed a better macroscopic repair than in older rabbits. However,
      the non-sutured wounds and burns did not heal in the fetuses, on the contrary,
      their opening increased from the time of the lesion. These results seem to
      suggest that wound repair in the fetus is more like a remodeling process than in
      older ages.

PMID- 1389967
TI  - [Total parenteral nutrition in rats].
AB  - Total parenteral nutrition (TPN) is difficult in rats because of their activity
      and aggressivity. On the other hand, this animal is an ideal experimental subject
      because it is easy to handle, resistant to infections, it has a short vital cycle
      and is very cheap. Long-term TPN can be simulated in rats after only relatively
      short periods of infusion. We report herein the results on TPN in rats obtained
      in our laboratory. Male Wistar rats (n = 86) weighing 170-225 g had a central
      line inserted under general anesthesia and received 330 mL/kg/day of fluids. They
      were divided into an Experimental Group (n = 70) that had a solution containing
      carbohydrates, proteins and lipids (310 Kcal/kg/day) and a Control Group (n = 16)
      receiving only saline and having free access to rat pellets. Total infusion time
      was 582.9 days. Twenty-five percent of the rats were withdrawn because of
      technical problems, 7% because of infection, 46% died and only 22% survived until
      the end of the experimental period. All animals gained weight. Those in the
      Experimental Group had significantly higher total protein and Chloride whereas
      those in the Control Group had higher leukocytes, BUN, liver weight, large bowel
      length and spleen relative weight. This TPN rat model is suitable for metabolic
      studies in the laboratory and should be further developed.

PMID- 1389968
TI  - [Nuclear magnetic resonance of anorectal malformations and persistent
      postoperative fecal incontinence].
AB  - We review our experience with Magnetic Resonance Imaging (MRI) in the evaluation
      of 6 patients showing anorectal malformation, and 4 more with persistent
      postoperative fecal incontinence. Preoperative sagittal, axial and coronal planes
      were studied with special consideration to the pelvic and vertebral structures.
      The excellent resolution of MRI allowed accurate identification of the pelvic
      musculature in all patients, including those with bizarre sacral abnormalities.
      MRI revealed structural anomalies not detected previously, such as teathering
      cord, intraspinal lipoma, presacral mass and renal malformation. In our
      institution, MRI has replaced the CT scan in the study of patients suffering of
      persistent fecal incontinence. In non operated on cases of anorectal
      malformations, MRI determines with extraordinary accuracy the location of the
      rectal atretic pouch, the actual pelvic muscular quality, and the detection of
      previously unsuspected associated anomalies.

PMID- 1389969
TI  - [Anorectal manometry in Hirschsprung disease].
AB  - To show the absence of inhibitory reflex of the anus (R.I.A.) by ano-rectal
      manometry is an important sign in the diagnosis of Hirschsprung's disease.
      Between 1989 and 1991, a series of 199 patients was studied. The patients were
      divided into two groups: 0-1 month and 1 month to 50 years. Both groups were
      subdivided into cases with or without clinical and radiological suspicion of
      aganglionism. In this series, R.I.A. was absent in 88 patients and present in
      111. Histologic study and follow-up confirmed the existence of aganglionism in 86
      patients, hyperganglionism in 1, anal stenosis in 8, cystic fibrosis in 4 and 1
      coeliac disease; the rest were megarecta to a greater or lesser degree. There was
      1 false negative, signifying a percentage of error of 0.5%.

PMID- 1389970
TI  - [Androgen insensitivity syndrome. Diagnosis and therapy].
AB  - Ten patients with complete or incomplete androgens insensitivity syndrome
      (A.I.S.) is reported. Diagnosis of A.I.S. is presented on the basis: clinical,
      phenotype, studies of sexual steroids specially androgens, gonadotropins, 5-alpha
      reductase activity and possible abnormality of androgen target cells from the
      genital skin. Histology of the testes is shown. Surgical treatment of these
      patients is reported, depending of the abnormality of the genitalia.

PMID- 1389971
TI  - [Abdominal trauma at a third-level pediatric hospital: study of 150 patients].
AB  - All paediatric patients with abdominal trauma admitted in our hospital from 1975
      to 1989 were retrospectively studied. We present 150 children with ages ranging
      from 1 to 14 years, mean age 6 +/- 2.6 years. Sixty-five percent of them were
      male. Trauma was classified as severe (37%) and mild (63%) and relationated with
      associated extra-abdominal injuries. The 42% of patients could be attended in
      other less specialized centres. Since 1982, severe abdominal trauma patient with
      parenchymal lesions of liver, kidney and spleen were treated according to a non
      surgical protocol without secondary complications.

PMID- 1389972
TI  - [Localization of the lower esophageal sphincter: a new formula].
AB  - The esophageal length in the study of patients with Gastroesophageal Reflux
      (G.E.R.) has the importance of assuring us of the correct position of the
      probe/sound of the esophageal ph-metering. We carried out a prospective study
      which correlated the size with the location of the Lower Esophageal Sphincter
      (L.E.S.), and we tried an approximation, greater than the one, obtained by other
      methods, in the measurement of the esophageal length, to obviate the manometric
      study, when our only aim was to insert correctly the probe/sound of the
      esophageal ph-metering.

PMID- 1389973
TI  - [24-hour simultaneous esophagogastric pH-metry in children].
AB  - Twenty-four-hour pH-monitoring of the lower oesophagus is the best test for
      diagnosis of gastro-oesophageal reflux (GER) because it is the only one allowing
      its quantification. Unfortunately, it is limited by the fact that acid exposure
      is not the only mechanism by which GER harms the oesophagus. In the last 12
      months we have introduced in our Institution simultaneous oeso-gastric pH
      metering using a double-channel recorder and gastric and oesophageal electrodes.
      This procedure enables us to know when gastric pH turns alkaline because od diet,
      mucus, hypoacidity or duodeno-gastric reflux (DGR) to the point of making
      oesophageal pH-metering useless. We report 7 illustrative cases of GER with
      prolonged episodes of gastric alkalinization leading to oesophageal pH-metering
      false negatives. In the near future, double pH-metering will very probably modify
      our current interpretation of conventional tracings.

PMID- 1389974
TI  - [Upper obstructive uropathies in newborns and infants. Our experience over the
      past 11 years].
AB  - We review 68 cases of ureterohydronephrosis in the newborn and nursling due to
      high urinary tract abnormalities, like ureteropelvic junction obstruction,
      obstructed megaureter, vesicoureteral reflux, renal duplication and simple
      ureterocele. A diagnostic evaluation is done, referred to his higher precocity,
      due to prenatal echographic screening. We evaluate also the surgical techniques
      employed, his complications and his indications. In the last five years, we have
      found that the definitive surgical correction in the neonatal period ive us good
      results.

PMID- 1389975
TI  - [Urodynamic diagnosis and treatment of neurogenic bladder dysfunction].
AB  - A group of 55 patients (28M, 27F) with neurogenic bladder dysfunction was
      studied. Patient age ranged from 1m. to 20 years (mean age 9.1 years). Most of
      the patients had neurogenic bladder secondary myelomeningocele (70%). The
      urodynamic investigations demonstrated detrusor hyperreflexia in 50 (poor
      compliance in 28p) detrusor areflexia in 3 and normal bladder in 2. Six patients
      hadn't incontinence and didn't need treatment. The rest (49p), couldn't be dry
      more than 2 hours. After treatment (anticholinergic, alpha adrenergic agonist,
      alpha-beta adrenergic agonist, I. C. and bladder augmentation), the continence
      was improved satisfactorily in 38 patients (77.5%). In conclusion, we think that
      early treatment from neonatal period, supported with urodynamic studies may
      prevent long-term renal damage and most patients with neurogenic bladder do not
      require surgical intervention to improve continence because it can be controlled
      satisfactorily by other means.

PMID- 1389976
TI  - [Anomalous course of a lipomeningocele].
AB  - A 9 months old male with a lipomeningocele developed progressive flaccid
      paraparesis with loss of deep tendon reflexes and sensation to pink prick on the
      lower extremities. The clinical picture was secondary to a tethered spinal cord
      syndrome associated to the lipomeningocele. Surgical untethering of the spinal
      cord was followed by clinical recovery over a 3 months period.

PMID- 1389977
TI  - [Gastric duplication associated with heterotopic pancreas].
AB  - Gastric duplications are the least frequent location for the alimentary tract
      duplications, these location is approximately 8%. We present a case of gastric
      duplication in a neonate, who had a palpable abdominal mass and feeding
      intolerance. Barium study of upper gastrointestinal tract and ultrasound showed
      an extrinsic compression of antrum and cyst abdominal mass. The surgical
      procedure consisted of total excision without violation of the gastric lumen.
      Gastric mucosal was found by hystological study. Heterotopic pancreatic tissue
      was also found on the major omentum closely gastric cyst duplication.

PMID- 1389979
TI  - [Duodenal atresia and heterotaxia].
AB  - We report two cases of duodenal atresia associated with corporal symmetry
      changes. The one of them presented a "situs inversus total" and the other one a
      Ivermak syndrome. The association between duodenal atresia and Ivermak syndrome
      has a very low incidence. We have not found references with respect to the
      association between duodenal atresia and "situs inversus totalis". The embryo
      genetic hypothesis that could relate both anomalies are discussed. Perhaps are
      not caused by chance.

PMID- 1389978
TI  - [The "abdominal zipper": a surgical surprise].
AB  - In our surgical department there are two kinds of mandatory reoperations: the
      second look and enterostomies. How many times are we thinking to use a zip in a
      laparotomy, for avoiding abdominal wall damage? The first experience using zip in
      a newborn with neonatal sepsis and intestinal ischemia is presented. This device
      allowed to check the bowel every day and to perform the appropriate surgery.
      Seven days after last surgery we removed the zip and closed the abdominal wall.

PMID- 1389980
TI  - Health for All. Second evaluation in the Americas, 1991.
AB  - In 1991, the fourth stage of surveillance and evaluation was implemented, on
      progress attained towards reaching the goals of Health for All by the Year 2000
      (HFA/2000). A regional report for the Americas was elaborated, to include the 28
      national reports received by PAHO and the quantitative information of 11
      countries and territories. The regional report was presented to and approved by
      PAHO Directing Council in September 1991. Following are the main conclusions.

PMID- 1389981
TI  - Mortality in the Americas 1950-1990.

PMID- 1389982
TI  - The economic impact of the cholera epidemic, Peru, 1991.
AB  - A summary is presented of some of the results of a study designed to determine
      the economic impact of the cholera epidemic in Peru. The study was carried out by
      economists Margarita Petrera, principal investigator, and Maibi Montoya,
      assistant investigator, sponsored by PAHO/WHO upon request of the Peruvian
      Multisectoral Commission for the Campaign Against Cholera.

PMID- 1389983
TI  - [Radical surgery in cancer of the thyroid: total thyroidectomy and prognostic
      factors].

PMID- 1389984
TI  - [Clinical considerations on spontaneous pneumothorax].
AB  - The authors, after confirming the social interest of spontaneous pneumothorax,
      report the results of their experience taking hint from it for some clinical
      considerations. They mention different therapies suggested for the treatment of
      this disease; particularly they dwell upon aspiration techniques considered today
      the treatment of choice in most cases. They conclude affirming that this
      technique improves results, diminishes risks and complications, and considerably
      reduces hospitalization.

PMID- 1389985
TI  - [Leiomyosarcoma of the rectum].
AB  - Two cases of leiomyosarcoma of the rectum observed between 1980 and 1990 are
      reported. Both patients underwent abdominoperineal resection: one is still alive
      at three years from surgery, whereas the other died for neoplastic diffusion
      after three years. Epidemiological, clinical and therapeutic features of this
      rare tumor are discussed.

PMID- 1389986
TI  - [Acute abdominal pain and appendicitis in childhood].
AB  - The diagnosis of acute appendicitis is still difficult to ascertain in children.
      However, a complete anamnesis, an accurate physical examination as well as a
      careful evaluation of other medical and surgical possibilities causing abdominal
      pain allow to arrive to a correct diagnosis in 80% of cases. Laboratory findings
      may be helpful but usually don't add further information. Each patient suspected
      to have appendicitis should be admitted to the hospital and kept under
      observation; if no improvement is registered during the following hours then a
      surgical exploration is needed. The surgeon, however, must be acquainted with the
      different medical affections causing abdominal pain in order to decide whether a
      laparotomy is required. The Authors report their experience in 426 patients
      submitted to appendectomy and stress the correlation between abdominal pain and
      intraoperative finding.

PMID- 1389987
TI  - [Emergency treatment of caustic lesions of the upper digestive tract].
AB  - The role of an early multidisciplinary approach to the management of upper
      digestive tract caustic lesions in the acute phase is stressed. The accurate
      evaluation of the lesions through early endoscopy, performed within 24-48 hours
      of ingestion, is the best means of assessing the degree of injury after caustic
      ingestion. Massive gastric and/or oesophageal necrosis, tracheoesophageal
      fistula, massive gastric haemorrhage, gastric and/or duodenal perforation are
      indications for emergency surgery. Management techniques of acute lesions are
      controversial because results of the different surgical procedures proposed are
      not satisfactory. Surgery of complications is mandatory, but up to date morbidity
      and mortality rates are still high.

PMID- 1389988
TI  - [Non-palpable lesions of the breast: identification, localization, significance].
AB  - The authors report the diagnostic protocol used in the Breast Disease Unit of the
      1st Surgical Department - University of Rome "La Sapienza" - (1987-1990) as well
      as the techniques for identifying and localizing nonpalpable lesions of the
      breast. Mammographic screening in women over 40 years, ultrasonography in women
      under 40 years, X-ray and ultrasound-guided fine needle aspiration and
      stereotactic guide wire placement with excisional biopsy, resulted to be
      diagnostic in 79 cases of carcinoma of the breast (2.0%) of which 13 (16.4%) were
      nonpalpable lesions. Moreover, the importance of nonpalpable lesions is
      discussed, pointing out how "very early" diagnosis of carcinoma of the breast
      plays a fundamental role with respect to both prognosis and treatment. The very
      early diagnosis of a "minimal" carcinoma ensures a significant increase in
      survival as well as more conservative surgical procedures that offer a better
      quality of life being less psychologically traumatic.

PMID- 1389989
TI  - [Postoperative infections: the use of thymostimulin (TP1) in patients at risk].
AB  - The authors report data related to 212 surgical patients at risk because
      immunocompromised. Patients were divided in two homogeneous groups, one treated
      with Thymostimulin and the other as a control group, all affected by severe
      pathologies. Patients presenting postoperative complications directly related to
      technical reasons were excluded. Morbidity, postoperative hospitalization and
      mortality were the parameters considered. Positive results were obtained in the
      treated group compared to controls. Therefore, it is Authors' opinion that the
      treatment with Thymostimulin in immunocompromised patients is important in order
      to avoid or reduce postoperative infection rates.

PMID- 1389990
TI  - [Single lung transplantation: experimental technique and functional results].
AB  - Single lung transplantation was performed in 22 pigs. The first 10 experiments
      were devoted to settle the surgical technique: in these cases we employed small
      animals (8-12 kg); technical difficulties and the high incidence of perioperative
      complications induced us to utilize bigger animals (greater than 20 kg) in the
      subsequent experiments. In the recipient, after left pneumonectomy we prepared
      the right pulmonary artery and encircled it with an inflatable silicon cuff
      connected to a reservoir positioned outside the chest cavity of the animal. The
      inflation of the cuff allows the complete occlusion of the right pulmonary artery
      and thus the functional evaluation of the isolated transplanted lung.
      Perioperative functional evaluation has been performed at different times till
      the third postoperative day, documenting the good status of the transplanted
      lung. This study confirms the possibility to employ pigs for experimental single
      lung transplantation to settle the surgical technique with economic and
      organizing advantages. Furthermore, it confirms the good results achieved in the
      dog, in which the occlusion of the contralateral pulmonary artery by means of an
      inflatable silicon cuff allows to evaluate the isolated transplanted lung
      function.

PMID- 1389991
TI  - Hazard Analysis and Critical Control Point system. The National Advisory
      Committee on Microbiological Criteria for Foods.

PMID- 1389992
TI  - Evaluation of the bacteriological quality of seafood.
AB  - Bacteria largely determine the quality of fresh and lightly preserved fish
      products. This paper surveys traditional and rapid methods for estimation of
      bacterial levels in seafood. The use of traditional agar techniques is discussed
      with reference to development of substrates and procedures suited for fish and
      fish products. This includes estimation of the bacteria specifically involved in
      the spoilage process. During the last decade, several microbiological rapid
      methods or principles (DEFT, microcolonies, Limulus lysate, ATP, conductance,
      microcalorimetry, reduction of trimethylamine oxide (TMAO)) have been suggested
      for estimating the bacteriological quality of seafoods. A brief survey of these
      methods and the results obtained is given. Preliminary results on development of
      poly- and monoclonal antibodies against Shewanella putrefaciens are mentioned.
      Future research may involve the development of DNA-probes against genes coding
      for specific spoilage reactions.

PMID- 1389993
TI  - A comparison of standard cultural methods for the detection of foodborne
      Salmonella.
AB  - The sensitivity of the standard cultural method of the International Organization
      for Standardization (ISO 6579 and ISO 3565 combined) was compared to that of the
      Health Protection Branch (HPB) procedure for the detection of foodborne
      Salmonella. Of 195 foods tested, 84 (43.1%) were found to contain salmonellae by
      one or more cultural conditions. Of these, 75 (89.3%) and 68 (81.0%) were
      identified by the ISO and HPB methods, respectively. The apparent lack of
      agreement between both methods likely stemmed from the low indigenous numbers of
      salmonellae in several food homogenates, and unequal transfer of the target
      microorganism into homologous ISO and HPB pre-enrichment broths. The
      sensitivities of the commercially available Muller-Kauffmann tetrathionate broth
      (MKTBG43, Oxoid CM343), and a closely-related medium prepared with Oxoid CM29
      tetrathionate base varied from 86.9 to 89.3%, and were deemed equivalent to that
      obtained with the ISO formulation of MKTBG43 (89.3%). Comparatively fewer
      contaminated samples were identified from selenite cystine (SC35) and selenite
      brilliant green (SBG35) enrichment cultures (82.1-83.3%). The high selectivity
      and saccharide-independent response of the bismuth sulfite agar medium warrants
      its consideration as a mandatory plating medium in ISO methodologies for the
      effective detection of typical and atypical biotypes of foodborne Salmonella spp.

PMID- 1389994
TI  - The contamination of pork with spoilage bacteria during commercial dressing,
      chilling and cutting of pig carcasses.
AB  - Swab samples from the surfaces of carcasses and cuts were obtained at various
      stages of the dressing, chilling and cutting operations in three pig processing
      plants. The aerobic microflora obtained from those swabs were enumerated and
      characterized. The flora on the skins of carcasses exiting the scalding tanks
      were dominated by Gram-positive organisms, with numbers about 10(3)/cm2. After
      dehairing, numbers were about 10(4)/cm2 with major fractions of Gram-negative
      organisms. Flora numbers and compositions were largely unaltered after the
      singeing operations, but lesser numbers were recovered after the carcasses were
      polished. Carcass dressing did not change the numbers on the skin. During the
      chilling of carcasses, the flora at two large plants altered little, but drying
      of the carcass surfaces at a smaller plant reduced the Gram-negative fraction of
      the flora. Numbers on serous and fat surfaces exposed during the dressing and
      cutting of carcasses were initially about 10(2)/cm2. That number was
      approximately maintained on finished skinned cuts produced at the smaller plant,
      but further contamination with lactobacilli and Brochothrix thermosphacta
      occurred during cutting. At the larger plants, the flora on skinned cuts were
      similar to those on skins, although further contamination with B. thermosphacta
      occurred at one plant.

PMID- 1389995
TI  - Rapid identification of Saccharomyces cerevisiae, Zygosaccharomyces bailii and
      Zygosaccharomyces rouxii.
AB  - Most strains of Saccharomyces cerevisiae, Zygosaccharomyces bailii and
      Zygosaccharomyces rouxii have been found to contain plasmid DNA. The sequences of
      the plasmids from these three yeasts are known to be different. We have used two
      primers within the plasmid from each yeast species in a multiplex polymerase
      chain reaction (PCR) to discriminate between these three yeasts. The primers were
      designed to give easily distinguishable fragment sizes when run on a simple
      agarose gel. Due to the sensitivity of PCR, crude cells can be used with no need
      to isolate DNA. The method is rapid when compared with current methods.

PMID- 1389996
TI  - Occurrence of Yersinia enterocolitica in milk and dairy products in Morocco.
AB  - A total of 227 samples of milk and dairy products were examined for the presence
      of Yersinia enterocolitica. Yersinia spp. were recovered from 11 of 30 raw milks
      (36.6%), one of 20 pasteurized milks (5%), 15 of 63 traditional fermented milks
      (23.8%), seven of 94 cheeses and one of 20 cream samples (5%). The overall
      incidence of Y. enterocolitica in milk and dairy products was 6.6%. The other
      Yersinia species were Y. intermedia, Y. kristensenii, Y. frederiksenii and Y.
      pseudotuberculosis. Y. enterocolitica was detected only in raw milk (30% of the
      samples), in traditional fermented milks (6.3%) and in raw milk-made cheese (4%).
      The majority of the Y. enterocolitica isolates were of biotype 1 (environmental
      strains). The Celfulodin-Irgasan-Novobiocin (CIN) Agar was found to be more
      efficient than the Mac Conkey Agar in the isolation of Yersinia organisms.

PMID- 1389997
TI  - Antibiotic and disinfectant susceptibility in Enterobacteriaceae isolated from
      minced meat.
AB  - The resistance of Enterobacteriaceae isolated from minced meat to antibiotics and
      to an amphoteric surfactant, was examined. Despite the wide range of antibiotic
      resistance occurring in the strains tested, resistance to the disinfectant was
      not observed.

PMID- 1389998
TI  - Distribution of saposins (sphingolipid activator proteins) in tissues of
      lysosomal storage disease patients.
AB  - Saposins are a group of small glycoproteins derived from a single precursor
      protein, prosaposin. Each of the four saposins are involved in lysosomal
      hydrolysis of various sphingolipids. Our recent investigations have shown that
      saposins accumulate in tissues of several lysosomal storage diseases patients,
      including those with Tay-Sachs disease and Gaucher disease. To obtain insight
      into the mechanism of accumulation and its pathological role, the subcellular
      distribution of saposins in brain from Tay-Sachs disease and in spleen of Gaucher
      disease were compared with that of GM2 ganglioside and glucocerebroside,
      respectively. In both Tay-Sachs brain and Gaucher spleen, saposins were found
      predominantly in light-density fractions while most of the GM2 ganglioside and
      glucocerebroside, respectively, were found in heavy-density fractions. These
      studies indicate that saposins that accumulate in these pathological tissues are
      not tightly associated with GM2 ganglioside or glucocerebroside.

PMID- 1389999
TI  - Dexamethasone-induced effects on B-50/GAP-43 expression and neurite outgrowth in
      PC12 cells.
AB  - Undifferentiated PC12 cells contain detectable levels of the nervous-specific
      protein B-50/GAP-43. Upon treatment with NGF or change of culture medium, B
      50/GAP-43 levels remained unchanged during the first 12 hours while
      neuritogenesis starts. Both, B-50/GAP-43 levels and neurite outgrowth peak at 24
      hours. These results suggest that in PC12 cells the amount of B-50 already
      present is sufficient to support the start of NGF-induced neuritogenesis,
      presumably by translocation from cytosolic compartments to the membrane. Addition
      of DEX reversed the rise in B-50/GAP-43 levels induced by either the change of
      medium or by NGF. In contrast, neurite outgrowth was inhibited to a lesser
      extent, although after 36 hours of pretreatment with DEX neurite length was lower
      than control. NGF was capable of enhancing B-50/GAP-43 levels both in the
      presence and absence of DEX. This corroborates data from others, who concluded
      that DEX and NGF exert their effects through different mechanisms, e.g.,
      transcription versus mRNA stabilization, respectively. The inhibitory effect of
      DEX under various conditions on both B-50 expression and neurite outgrowth in the
      normal PC12 cell line demonstrates the tight coupling of these parameters that
      might be indicative of a threshold effect of B-50 levels on neurite outgrowth.

PMID- 1390000
TI  - Effects of chronic treatment of haloperidol and clozapine on levels of G-protein
      subunits in rat striatum.
AB  - Chronic administration of typical neuroleptic drugs, such as haloperidol, causes
      the supersensitivity of brain dopamine D2 receptor in striatum and limbic
      regions, while the atypical neuroleptic clozapine does not. In order to
      understand the mechanism of their action at a molecular level, studies were
      carried out to assess the effects of chronic treatment of these drugs on the
      levels of G-proteins in the rat striatum using the Western blot method. Results
      of the present study demonstrate that the treatment with haloperidol or
      clozapine, respectively, down-regulate or up-regulate the levels of G proteins.
      Quantitative immunoblotting, using site-directed specific antisera, demonstrated
      that chronic treatment with haloperidol down-regulates Gi alpha, Gs alpha, and
      beta subunits while chronic treatment with clozapine upregulates Gi alpha, Gs
      alpha, and beta subunits. Neither of these drugs has any effect on the levels of
      Go alpha.

PMID- 1390001
TI  - Isolation and structural characterization of Drosophila TDVDHVFLRFamide and
      FMRFamide-containing neural peptides.
AB  - An extract of adult Drosophila melanogaster was separated by gel exclusion, ion
      exchange, and reversed-phase chromatography. Four peptides, each with an 
      ArgPheNH2 C-terminal sequence, were identified by radioimmunoassay. The primary
      sequences were determined by Edman degradation and confirmed by mass spectrometry
      and sequence-specific radioimmunoassay. Three of the peptides are encoded by
      Drosophila proFMRFamide: AspProLysGlnAspPheMetArgPheNH2 (DPKQDFMRFamide),
      ThrProAlaGluAspPheMetArgPheNH2 (TPAEDFMRFamide), and SerAspAsnPheMetArgPheNH2
      (SDNFMRFamide). A novel Drosophila peptide ThrAspValAspHisValPheLeuArgPheNH2
      (TDVDHVFLRFamide) was also isolated. TDVDHVFLRFamide is structurally related to
      peptides isolated from chicken, cockroach, locust, and snail; the cockroach,
      fruitfly, and locust peptides differ only by the N-terminal amino acid residue.
      Two Drosophila neural genes, dsk and FMRFamide, are known to encode -ArgPheNH2
      containing peptides; however, neither encodes TDVDHVFLRFamide, indicating that
      Drosophila contains another precursor encoding -ArgPheNH2 peptides.

PMID- 1390002
TI  - Crystallographic and chemical properties of Mg-containing apatites before and
      after suspension in solutions.
AB  - Mg-containing synthetic apatites were prepared and then incubated in unbuffered
      0.9% NaCl solution and in buffered 0.1 M CH3COOK solution (pH 7.4) at 37 degrees
      C to examine the changes in their crystallographic and chemical properties after
      suspension in these solutions. After one month of incubation, the magnesium (Mg)
      content in the samples decreased greatly, especially in samples with higher Mg
      content. The a and c axis dimensions of the samples changed with the decrease of
      Mg content. On the other hand, Mg concentrations in both solutions increased more
      than the Ca concentrations. Mg-substituted beta-tricalcium phosphate (beta-TCP),
      or whitlockite, formed from solutions with high Mg concentration. These results
      show that Mg-containing apatites dissolve to a greater extent than Mg-free
      apatites with the subsequent reprecipitation of Mg-poor apatites. In addition,
      the high Mg/Ca in solution favoured the reprecipitation of Mg-containing beta
      TCP.

PMID- 1390003
TI  - Effect of magnesium deficiency on 15-hydroxyeicosatetraenoic acid in cultured
      human umbilical arterial endothelial cells.
AB  - Effects of magnesium deficiency on the production of 15-hydroxyeicosatetraenoic
      acid (15-HETE) and cytosolic free calcium concentration in human umbilical
      arterial endothelial cells were studied by radioimmunoassay. 15-HETE release by
      endothelial cells incubated with normal magnesium media (900 microM Mg2+) for 24
      h was 2.2 +/- 0.3 ng/mg protein. 15-HETE release gradually increased in
      proportion to decrease of magnesium. Low magnesium media (180 microM Mg2+) caused
      an increase in 15-HETE release in a time-dependent manner. Cytosolic free calcium
      concentration of endothelial cells in normal magnesium media fluctuated between
      129.4 nM and 134.2 nM during a 24 h period. Low magnesium media (180 microM Mg2+)
      caused a time-dependent rise in cytosolic free calcium concentration which is
      consistent with a time-dependent increase in H-HETE release. High magnesium
      medium (1800 microM Mg2+) did not have any effect on cytosolic free calcium
      concentration or 15-HETE production. In conclusion, 15-HETE release by
      endothelial cells was stimulated by increase in cytosolic free calcium
      concentration induced by magnesium deficient media. It is suggested that
      magnesium deficiency induces atherosclerosis via increase in 15-HETE production.

PMID- 1390004
TI  - Influence of ethyl alcohol when given alone or in combination with potassium
      and/or magnesium supplements on ventricular fibrillation threshold levels in
      laboratory rats.
AB  - Five groups of rats were studied in an investigation to determine whether changes
      in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH)
      is given alone or in combination with K+ and/or Mg2+ supplements; the first group
      (n = 20) served as controls, the second (n = 18) was given only EtOH, the third
      (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18)
      EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on
      each day. One rat heart was perfused using the Langendorff apparatus and the
      other used for tissue electrolyte analyses. A significant fall in the mean VFT
      (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats
      given EtOH solution as drinking water for 9 months, and a significant increase in
      the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9
      +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/-
      1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition,
      an increase in the heart rate was observed in the group supplemented with Mg2+
      (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in
      the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10
      beats/min; P less than 0.002) compared to controls. There was no significant
      change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1390005
TI  - Beneficial effects of a calcium antagonist, nifedipine, on death and
      cardiovascular calcinosis induced by dietary magnesium deficiency in adult mice.
AB  - The effects of nifedipine on the survival rate and the cardiovascular calcinosis
      were investigated in dietary magnesium (Mg)-deficient mice. Male mice aged 8 to
      10 weeks were fed with a diet which was either normal (0.07%) or deficient
      (0.007%) in Mg for 30 d. Nifedipine was added to the Mg-deficient diet for 30 d
      in a concentration of 1000 ppm. About 65% of Mg-deficient mice died within 30 d.
      In contrast, all the nifedipine-treated mice survived for 30 d. Mg-deficient mice
      showed hypomagnesaemia and hypocalcaemia which were not influenced by nifedipine
      treatment. Aortic and cardiac calcium contents increased in Mg-deficient mice,
      and these increments were normalized by nifedipine treatment. These results
      suggest that the life-saving effect of nifedipine in Mg-deficient mice might
      relate, at least in part, to the prevention of a deleterious increase in Ca in
      cardiovascular tissues.

PMID- 1390006
TI  - Serum and erythrocyte magnesium concentrations and migraine.
AB  - Most people suffering from migraine present a hypersensitivity of the cervico
      facial muscles, which may be linked to magnesium deficit. This paper describes a
      comparative study of serum and erythrocyte magnesium levels in 79 migraine
      patients and 55 controls. Serum magnesium did not differ significantly in either
      group, but some values were quite low. On the other hand, there was a
      significantly greater erythrocyte magnesium deficit in persons suffering from
      migraine than in controls (in both female and male subjects). This fact
      correlates with the improved state of migraine patients (already ascertained in
      earlier studies) following treatment consisting of the intake of magnesium-rich
      water. The findings support the hypothesis of a magnesium deficit in people
      suffering from migraine and raise the problem of the relationship between
      migraine and other pathologies, including chronic magnesium deficit, latent
      tetany due to magnesium deficit, mitral valve prolapse, and allergy.

PMID- 1390007
TI  - Magnesium and blood pressure. I. Animal studies.
AB  - The relationship between experimental magnesium deficiency and blood pressure is
      complex and still the subject of much debate. The effect of Mg deficiency and
      blood pressure in Wistar rats receiving a Mg deficient diet (0.080 g/kg) for 40
      weeks was examined. Deficient rats, when compared to controls, showed an initial
      transitory phase of hypotension, followed by normalization of blood pressure and
      then hypertension beginning after 15 weeks on the deficient diet. During the
      whole experimental period, heart rate was significantly increased in deficient
      rats as compared to controls. The fact that hypotension resulting from Mg
      deficiency of short duration can be inhibited by antihistamines and by
      indomethacin suggests that various mediators seen during the inflammatory period
      of Mg deficiency could be involved. Mg deficiency of long duration was
      accompanied by hypertension. When Mg-deficient rats received the control diet for
      a period of 3 weeks, Mg supplementation only partially corrected the
      hypertension. The hypertension was not a consequence of stimulation of the renin
      angiotensin system since the plasma renin activity was not modified and ACE
      activity was reduced. These deficient rats showed a significantly lower
      vasopressor response to noradrenaline than control rats. Several factors such as
      increase in collagen, changes in elastin and arterial elasticity, total lipid
      content, and calcifications may account for the hyporesponsiveness to contractile
      agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390009
TI  - Inhibition of aluminium toxicity by magnesium and citric acid in tobacco tissue
      culture.
AB  - Using tobacco callus tissues the authors studied the antagonism of magnesium and
      aluminium, and the inhibition of aluminium toxicity by magnesium and citric acid,
      as expressed by their effect on growth and alkalod content. In response to an
      increase in the concentration of MgSO4 in the culture medium the fresh weight of
      the cultures significantly increased, while with an increase in Al2(SO4)3 growth
      decreased, 2 mM causing a high degree of inhibition. The toxic effect of
      aluminium was less marked when Mg was present at a concentration higher by an
      order (antagonistic inhibition). When citric acid was added to the culture
      medium, promoting complex formation with Al, the toxic effect of Al was not
      apparent. The nicotine content of the tissues was in each case inversely
      correlated with the magnitude of biomass formation.

PMID- 1390008
TI  - Magnesium and blood pressure. II. Clinical studies.
AB  - Magnesium deficit may be considered as a cardiovascular risk because of its
      aetiopathogenic role in the genesis of atherogenous dyslipidaemias and the so
      called "idiopathic" mitral valve prolapse. It does not, however, constitute a
      major antihypertensive factor, though it may sometimes be an accessory co-factor.
      Plasma magnesium is generally normal in untreated hypertensive patients and
      normotension is the rule during magnesium deficit. An inverse relationship
      between magnesium and renin in the plasma of hypertensives has not been
      confirmed. In practice, plasma magnesium seems to be related to the evolution of
      the disease. An inverse correlation between blood pressure and erythrocyte total
      and free magnesium levels has been observed in diverse selected populations but
      no adjustment has been made in these studies for important covariables. A weak
      positive association between blood pressure and erythrocyte free magnesium was
      lost in a multivariate regression analysis. As a rule there is no difference
      between erythrocyte, leucocyte, and lymphocyte magnesium in hypertensives and
      controls. More often no relation between urinary magnesium and blood pressure is
      observed. Daily urine magnesium may be increased with increased excretion of
      urine adrenaline. Epidemiological data on dietary magnesium, particularly in
      drinking water, should be carefully scrutinized: these studies do not establish a
      major role for magnesium as an antihypertensive factor but confirm the importance
      of magnesium deficit as a nephrocardiovascular risk factor and sometimes gives
      support for a role of magnesium as an antihypertensive cofactor. The use of
      magnesium-depleting drugs in hypertensive patients may induce magnesium depletion
      which must be palliated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390010
TI  - Magnesium, adenosine triphosphate, and catecholamine complexes: application of
      new means of identifying solute-solute interactions of biological significance
      using NMR chemical shift data.
AB  - The interaction of magnesium ions with biomolecular species is fundamental to the
      regulation of many biological processes. A mathematical technique to investigate
      such interactions is described. The concept of a pseudo-formation curve is
      discussed and the relevance and applicability of such constructions to the study
      of solute-solute interactions is outlined. Analysis of curves based on the
      published variation of chemical shift data of various nuclei of adrenaline and
      dichloroisoprenaline in aqueous solution, in the presence of increasing
      concentration of the complex Mg-ATP, is described. Unambiguous indentification of
      specific interactions and the stability of the species produced is shown to be
      feasible. Some variation of the values of formation constants deriving from
      different nuclei reflects the significance of molecular environmental factors on
      the parameters used.

PMID- 1390011
TI  - New treatments for prostate cancer: do they improve survival?

PMID- 1390012
TI  - Cardiac emergencies in the cancer patient.
AB  - Cardiac emergencies may be encountered during the management of patients with
      cancer, both in those with underlying cardiovascular disease and those with no
      previous history of cardiac problems. Both surgical and medical cancer treatment
      modalities may exacerbate preexisting cardiac conditions. Some antineoplastic
      agents can adversely affect the coronary arteries, myocardium, or pericardium. It
      has also been recognized that cardiac damage due to radiotherapy and chemotherapy
      may become clinically significant many years after therapy has been completed.
      Treatment of urgent cardiac problems in the cancer patient may differ from that
      recommended for other patient groups, since many cancer patients are not ideal
      candidates for some of the newer cardiac agents. Management of these conditions
      must therefore be tailored to the individual patient.

PMID- 1390014
TI  - New blood test available for detecting CML and other adult leukemias.

PMID- 1390013
TI  - Etiology and current management of cancer-related hypercalcemia.
AB  - Important new information has been gained concerning the etiology of cancer
      related hypercalcemia and thus treatment recommendations are changing. The most
      common cause of hypercalcemia in cancer patients is the parathyroid hormone-like
      peptide, PTH-RP. Patients with elevated serum calcium due to elaboration of
      parathyroid hormone-like peptide commonly present with hypophosphatemia and a
      relatively resistant form of hypercalcemia. Our new knowledge has led to
      recommendations against massive amounts of IV fluids and large doses of
      diuretics, which restore normocalcemia in only a minority of patients. New potent
      drugs such as pamidronate and gallium nitrate directly inhibit accelerated bone
      resorption. Thus, consideration should be given to the early administration of
      antiresorptive drugs immediately after intravascular volume has been repleted and
      urinary output has been established.

PMID- 1390015
TI  - Clinical trials referral resource. High Priority Trials.

PMID- 1390016
TI  - Neuropsychotropic drugs as adjuncts in the treatment of cancer pain.
AB  - Opiates remain the mainstay of cancer pain treatment, used in a logical and
      stepwise fashion with adjunctive therapies as needed. Certain neuropsychotropic
      drugs may enhance the analgesia produced by opiates and may occasionally be used
      in place of opiates. Some of these drugs may also provide additional psychoactive
      benefits. The types of neuropsychotropic drugs that may be useful in treating
      cancer pain include the tricyclic antidepressants, anticonvulsants, neuroleptics,
      antihistamines, psychostimulants, and benzodiazepines, as well as systemic local
      anesthetics. This article reviews the general principles of using adjunctive
      medications to achieve maximal analgesic benefit with the least number of side
      effects, and describes each class of neuropsychotropic drug, their proposed
      mechanism of analgesia, and appropriate use in cancer patients.

PMID- 1390017
TI  - Improving communication with cancer patients.
AB  - Although much more information is being disclosed to cancer patients than in the
      past, there is still considerable disagreement about how much information should
      be conveyed. This paper reviews the basic elements of informed consent, examines
      some of the major barriers to effective communication, and suggests ways in which
      physicians can enhance communication with their cancer patients. Physicians are
      urged to evaluate patients in terms of their coping and information-seeking
      styles and to keep in mind that most patients want information. In fact, studies
      show that giving patients adequate information usually impacts positively on
      their psychological and physical well-being.

PMID- 1390018
TI  - Carotid endarterectomy in the elderly.
AB  - The records of 146 patients 80 years of age or older who underwent 183 carotid
      endarterectomy operations from 1964 through 1990 were reviewed to determine
      surgical risk. The indications for operation were asymptomatic patients with
      carotid stenosis (n = 36); ipsilateral transient ischemic attacks (n = 46);
      ipsilateral stroke (n = 28); ipsilateral retinal embolus (n = 15);
      nonlateralizing symptoms (n = 40); and asymptomatic side in patients with
      contralateral symptoms (n = 18). Postoperatively, three patients (1.6% of
      operations) had a stroke with a residual deficit and three (1.6%) died. All
      deaths were from myocardial infarction. For comparison, during the same time
      period, the combined stroke with residual deficit and death rate for patients
      less than 80 operated upon for similar indications was 3.5%. Since 80-year-old
      patients have a life expectancy of at least five years, the authors conclude that
      elderly patients should be evaluated for carotid endarterectomy using criteria
      similar to that used for younger patients.

PMID- 1390019
TI  - Early results of infrainguinal arterial reconstruction with a modified biological
      conduit.
AB  - We implanted 112 glutaraldehyde-fixed bovine carotid artery grafts (BioPolyMeric
      [BPM]) for infrainguinal reconstruction in 107 legs of 98 patients. Indications
      for surgery were disabling claudication in 28%, rest pain in 33% and tissue loss
      in 39%. In 32%, BPM bypass followed failed ipsilateral reconstruction. Autologous
      vein was either absent or inadequate in 60% of cases. BPM was used preferentially
      over vein in above-knee bypasses. The distal anastomosis was to the above-knee
      popliteal artery in 40%, to the below-knee popliteal artery in 35%, and to the
      tibial arteries in 25%. Follow-up was available from one to 25 months, with a
      mean of nine months. Wound complications developed after 9% of operations,
      including seven (6%) graft infections. Both patent grafts that became infected
      were salvaged. Four patients (4%) died within 60 days of surgery due to cardiac
      complications. Life-table primary and secondary patencies of all grafts were 64%
      and 65% at one year, and 48% and 62% at two years, respectively. The only factor
      significantly affecting graft patency was the location of the distal anastomosis
      (p < .01). Primary patencies at one and two years to the above-knee popliteal
      artery were 90% and 80%, to the below-knee popliteal artery were 56% and 37%, and
      to the infrapopliteal arteries were 34% and 26%. Bypass to 16% of extremities
      resulted in amputation, including 5% that were amputated with patent grafts. No
      limb loss occurred as a result of operation for claudication. In conclusion, BPM
      grafts provide early results comparable to saphenous vein above the
      knee.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390020
TI  - Spontaneous peripheral arterial microembolization.
AB  - Over a seven year period 52 patients having a clinical diagnosis of spontaneous
      peripheral arterial microembolization were identified. Sixty-one percent of
      patients were female, 15% were diabetic, and 73% used tobacco chronically. A
      striking finding was the very high incidence of associated systemic disorders
      such as thrombocytosis (8), polycythemia vera (3), metastatic adenocarcinoma (3),
      or collagen disease requiring steroid therapy (4). Forty-nine patients had
      significant proximal arterial lesions as the origin of their emboli. Three
      patients had digital ischemia as a result of increased platelet aggregation
      without arterial obstruction. Forty-eight patients underwent surgical therapy.
      Operative mortality was 4% and overall limb salvage in survivors was 96%. The
      clinical syndrome of arterial microembolization may result from several
      pathophysiologic mechanisms including cholesterol embolization from ulcerated
      plaques, fibrino-platelet aggregation in patients with hematologic disorders, or
      dislodgement of mural thrombus in those with aneurysmal disease. We observed
      aortoiliac disease to be more frequent than femoral-popliteal disease, and both
      were amenable to surgical correction. We conclude that the genesis of arterial
      microembolization is multifactorial and that a variety of systemic diseases may
      work in concert with atherosclerotic arterial disease to produce this clinical
      syndrome. Prompt recognition and appropriate treatment of this disorder can yield
      high rates of limb salvage.

PMID- 1390021
TI  - Extrahepatic portal vein aneurysm: report of a case treated by thrombectomy and
      aneurysmorrhaphy.
AB  - Extrahepatic portal vein aneurysm is a rare condition with only 15 cases before
      ours being reported in the English literature. The etiology is thought to be
      congenital, secondary to portal hypertension or associated with abnormal weakness
      of the vein wall. It often presents in conjunction with major gastrointestinal
      bleeding, but may occur with minimal or no symptoms. Diagnosis is made with color
      duplex ultrasound, computed tomographic scan, venous phase mesenteric
      angiography, magnetic resonance imaging, or splenoportography. Thrombosis,
      rupture, and pressure effects are the major complications of portal vein
      aneurysm. Shunting procedures are recommended in cases with portal hypertension
      secondary to liver disease. We report the first case treated by thrombectomy and
      aneurysmorrhaphy with a successful 10 year follow-up. This procedure should be
      considered to preserve portal vein flow when portal hypertension is absent or is
      secondary to the aneurysm itself.

PMID- 1390022
TI  - Bypass to the lateral circumflex femoral artery.
AB  - Two patients with severe aortoiliac disease presented with total occlusion of all
      major femoral arteries, including the distal profunda femoris artery. Bypass to
      the lateral circumflex femoral artery, the most proximal branch of the profunda
      femoris artery, was successful in each patient. One patient had a bifurcated
      Dacron graft implanted from the aorta to the lateral circumflex femoral artery on
      each side. No sequential bypass to more distal vessels has since been necessary.
      The second patient underwent bypass to the lateral circumflex femoral artery from
      the contralateral femoral artery using saphenous vein. The procedure obviated the
      need to revise an above-knee amputation. The lateral circumflex femoral artery
      can provide suitable outflow in patients with thrombosis of the entire profunda
      femoris artery.

PMID- 1390023
TI  - Technique and results of vascular endoscopy in arterial and venous
      reconstructions.
AB  - In an effort to maximize results, vascular endoscopy was used in our institution
      to monitor arterial and venous reconstructions. Since 1982, angioscopy was
      applied as a control method in 182 venous thrombectomies to treat iliofemoral
      thrombosis and 114 aortoiliac thromboendarterectomies. Of the cases with venous
      thrombectomy reviewed, 50% were incomplete by endoscopic evidence; of these, in
      80% the remaining clots could be partly or completely removed. Additionally, in
      six patients a venous spur was found. Of 114 attempted aortoiliac
      thromboendarterectomies, only 91 could be completed. In the remainder, endoscopic
      evidence of persistent intimal flaps forced us to bypass the affected segments.
      With further miniaturization of the angioscopes, the method was also applied to
      check vessel repair on small-caliber arteries. In an initial study with 220
      femorodistal bypasses we were unable to find a statistically significant
      difference of primary patency in grafts that were endoscopically controlled or
      not. In the learning phase with the in situ technique, we identified competent
      valve remnants in 40%, but this rate could be reduced to 12.7% with growing
      experience in valvulotomy. We conclude from our data that angioscopy is very
      helpful in assessing the morphological integrity of aortoiliac
      thromboendarterectomies and venous thrombectomies. The actual value in
      infrainguinal arterial reconstructions still remains to be proven.

PMID- 1390024
TI  - Neurovascular lower extremity complications of the lithotomy position.
AB  - The lithotomy position is commonly used during the performance of a variety of
      abdominal and pelvic operations. Previous publications reporting complications
      with these operations have been largely anecdotal. We report our experience with
      eight patients over the past four years who have suffered serious lower extremity
      complications following operations in which the lithotomy position was used. The
      average time in the lithotomy position for our patients was 7.4 hours (range: 3.7
      12 hours). The mean interval between the original operation and the secondary
      operation to treat the lower extremity complication was 18.9 hours (range: 2-51
      hours). The average hospital length of stay for these patients, 38.4 days (range:
      11-119 days), was often prolonged as a direct result of their limb complication.
      Serious lower extremity complications may result from operations in which the
      lithotomy position is used. To prevent such complications, strict attention
      should be paid to the positioning of the limbs in the operating room and the time
      in the lithotomy position should be minimized. Perioperative monitoring of the
      lower extremity circulation and compartment pressures are essential in these
      patients since early detection and treatment of these complications is the only
      way to prevent permanent limb injury.

PMID- 1390025
TI  - Arterioureteral fistula after extended resection of pelvic tumors: report of
      three cases and review of the literature.
AB  - Arterioureteral fistulas are rare. Three patients with arterioureteral fistulas
      complicating extended resection of pelvic tumors associated with bilateral
      cutaneous ureterostomy in the right lower quadrant are reported. In one case, the
      fistula involved the left ureter, the right common iliac artery, and the inferior
      mesenteric artery. Pathological iliac artery, pelvic cancer, or operated ureteral
      stones are often incriminated in the genesis of ureteroarterial fistulas.
      Insertion of a ureteral catheter has been found to be the main promoting factor.
      The common iliac artery is involved frequently. Clinical presentation is often
      limited to gross hematuria, whereas complementary investigations have not proved
      to be sensitive. Surgical treatment is often complex, but must be undertaken
      early, even in the absence of absolute proof of diagnosis, in order to preclude
      uncontrollable massive hemorrhage.

PMID- 1390026
TI  - Superior mesenteric arteriovenous fistula after ileal resection.
AB  - Postoperative superior mesenteric arteriovenous fistula is very rare. We report
      the case of a 55-year-old woman in whom the discovery of an abdominal bruit led
      to the diagnosis of superior mesenteric arteriovenous fistula seven years after
      ileal resection. The clinical and pathophysiological aspects, as well as the
      therapeutic modalities, of this rare lesion are reviewed.

PMID- 1390027
TI  - Double popliteal artery of congenital origin.
AB  - An exceptional unilateral right double popliteal artery was discovered by chance.
      After a review of the possible causes of embryological developmental
      abnormalities, the most likely hypothesis is that of persistent sciatic artery.

PMID- 1390028
TI  - Renal arteriovenous fistula after nephrectomy.
AB  - Postnephrectomy renal arteriovenous fistulas are rare. An arteriovenous fistula
      of the right renal pedicle was discovered in a 37-year-old woman who had
      undergone nephrectomy for renal tuberculosis nine months previously, after she
      had complained of dyspnea and pain in the right flank. The fistula was confirmed
      on arteriograms. Proximal ligation of the artery and distal ligation of the vein
      were followed by an uneventful recovery. Twelve months later, the patient was
      asymptomatic. Even though complete excision of the fistula represents the ideal
      treatment of this type of lesion, simple ligation can provide good results when
      the size of the fistula contraindicates embolization.

PMID- 1390029
TI  - Rehabilitation of patients with thoracic outlet syndrome.
AB  - A series of physical therapy protocols is proposed for patients with thoracic
      outlet syndrome. The anatomic findings dictating certain physical therapeutic
      approaches are outlined. General principles of physical therapy that stem from
      these findings are suggested, and a specific protocol for the physical therapy
      regimen is given. An appropriate physical therapy program for thoracic outlet
      syndrome patients with symptoms of mild-to-moderate severity can avoid early
      surgery. Degradation of symptoms or invalidating functional compromise indicates
      a referral to surgery. Physical therapy cannot replace surgery in severe or
      complicated forms of thoracic outlet syndrome with vascular or neurologic
      compromise.

PMID- 1390030
TI  - Transthoracic endoscopy for upper thoracic chemical sympathectomy.
AB  - Beginning in April 1989, we have performed eight upper thoracic chemical
      sympathectomies by transthoracic endoscopy. The indications were occlusive
      arterial disease in four patients and Raynaud's syndrome and palmar hyperhidrosis
      in two patients each. Transthoracic endoscopy was performed under general
      anesthesia, through the third costal interspace on the anterior mid-clavicular
      line. Five ml of phenol were injected into the parietal pleura covering the three
      proximal thoracic ganglia. The duration of thoracic drainage was 24 hours. The
      postoperative course was uneventful except for one case of subcutaneous emphysema
      and transient Horner's syndrome in three instances. There were no initial
      failures. Because of its simplicity and the short hospitalization period,
      chemical sympathectomy by transthoracic endoscopy constitutes a valuable
      alternative to conventional surgery. This technique is, however, limited in the
      case of antecedent pleuropulmonary disorders.

PMID- 1390032
TI  - Cutaneous viral infections.

PMID- 1390031
TI  - Diagnostic imaging in peripheral vascular disease.

PMID- 1390033
TI  - Molluscum contagiosum.
AB  - This in-depth review considers the known virological and molecular biological
      aspects of the molluscum contagiosum virus. Furthermore, the epidemiology of its
      infection of human skin is detailed, and the clinical, histological, and
      therapeutic information available at this time are cataloged. It is concluded
      that molluscum contagiosum has become an almost common skin disease that can
      prove very difficult to eradicate from an infected patient.

PMID- 1390034
TI  - The natural history of recurrent oral-facial herpes simplex virus infection.
AB  - Oral-facial herpes simplex virus infection is a common, worldwide affliction on
      which neither public health procedures, vaccines, nor antiviral chemotherapy have
      yet to have a significant clinical impact. Careful examination of the
      pathogenesis and clinical features of this illness could lead to insights and a
      rationale for new and more effective preventive and therapeutic measures. The
      resistance of recurrent herpes simplex labialis to antiviral chemotherapy may be
      caused in part by inoculation of the skin simultaneously at multiple foci, such
      that only a few cycles of virus replication are needed before there is
      coalescence of the foci, destruction of the epidermis, and clinical lesion
      formation. Studies of herpes simplex labialis induced by ultraviolet radiation
      have suggested that there is a subpopulation of lesions that develop immediately
      after irradiation and that are refractory to chemotherapy. The difficulty finding
      a treatment for herpes simplex labialis may in part be methodological. Clinical
      trial protocols for antiviral drugs should target susceptible lesion subgroups
      and specific stages of the disease.

PMID- 1390035
TI  - Erythema multiforme and latent herpes simplex infection.

PMID- 1390036
TI  - Natural history of varicella zoster virus.
AB  - The varicella zoster virus (VZV) is a herpesvirus responsible for two distinct
      clinical disorders, primary varicella (chickenpox) and zoster (shingles). Primary
      varicella is a common childhood disease in Western countries, which presents as
      pruritic macules, papules, vesicles, pustules, and crusts, usually on the back,
      chest, face, and abdomen. In immunocompetent children, chickenpox is generally a
      mild disease with little morbidity and rare mortality. Primary varicella is
      associated with more morbidity in adults. Following resolution of primary
      varicella, VZV persists in a latent form in dorsal ganglion cells for what is
      usually an extended period of time. For reasons that are still poorly understood,
      VZV can later start replicating in the ganglion, producing severe neuralgia and
      spread of the virus down the sensory nerve. Vesicles then appear on the skin in
      the distribution of this nerve, producing the characteristic dermatomal rash of
      shingles. The vesicles progress to pustules, then to crusts that eventually are
      lost. Scarring and changes in pigmentation can result, but the most frequent
      sequela of zoster is postherpetic neuralgia, which is usually most severe in the
      elderly. Primary varicella or herpes zoster in immunocompromised patients can
      sometimes involve internal organs (eg, lungs, liver, brain) resulting in high
      rates of morbidity and mortality. Congenital VZV infection is uncommon but can
      result in severe congenital malformations. A Tzanck smear can be useful to
      demonstrate a herpesvirus infection, but confirmation of VZV as the cause of the
      infection requires at least one of the following tests: culture, serology, direct
      immunofluorescence staining, or molecular techniques.

PMID- 1390037
TI  - Treatment of postherpetic neuralgia.
AB  - Postherpetic neuralgia (PHN) is the most common and feared complication of herpes
      zoster. The more severe and painful the initial zoster outbreak, the more likely
      that PHN will develop, with elderly patients being at greatest risk. There are no
      proven treatments that have a large impact in reducing the risk of PHN. Tricyclic
      antidepressants are the mainstay of treatment for established PHN, aided by
      transcutaneous electrical nerve stimulation, physical therapy techniques, and
      cautious use of other medications. Topical agents, such as capsaicin, aspirin,
      and lidocaine, may soon become one of the mainstays of therapy for PHN.

PMID- 1390038
TI  - Rational use of acyclovir in the treatment of mucocutaneous herpes simplex virus
      and varicella zoster virus infections.
AB  - The herpes family of viruses establishes latent infection in neurons and produces
      a spectrum of acute and recurrent clinical disease. Therapies to terminate the
      neurolatency or to enhance host responses are not yet available. Current therapy
      consists of antiviral drugs, which interfere with viral replication, can
      favorably alter the signs and symptoms of symptomatic disease, and act as
      prophylaxis against recurrent disease. Because the severity of acute and
      recurrent herpes group infection varies greatly between individuals, proper
      selection of patients to be treated with antiviral therapy is important. In
      general in immunocompetent patients, antiviral therapy has the greatest potential
      benefit for patients early in the course of primary or initial disease, or for
      patients with frequent and/or severe recurrent disease. Patients late in acute
      disease or with infrequent and/or mild recurrent disease are very unlikely to
      benefit from antiviral therapy. With immunocompromised patients, antiviral
      therapy is of the greatest potential value. By careful selection of patients, the
      clinician can maximize the benefits of antiviral therapy for patients with
      cutaneous herpes group viral infections.

PMID- 1390039
TI  - Inactivated hepatitis A vaccine.

PMID- 1390040
TI  - Diarrhoeal diseases. Gastroenteritis and cholera epidemic, 1991.
AB  - In summary, during 1991, a substantial cholera outbreak occurred in Nepal. It
      presented as one of the causes of a multicausal gastroenteritis epidemic which
      reportedly resulted in nearly 92,000 cases and 1,800 deaths. The 1991 epidemic
      appeared to have been more severe with a longer duration than the epidemic which
      occurred in 1990. The overall case-fatality rate was 2.0%. Cholera was confirmed
      in 63% of faecal specimens processed, compared with 46% during the 1990 epidemic.
      Specimens from the first and last laboratory-confirmed cases were collected on 14
      June and 26 September 1991, respectively. The presence of cholera was confirmed
      in all 5 development regions in the country. Contaminated public water supplies
      probably contributed to sustaining disease transmission, at least in urban areas.

PMID- 1390041
TI  - Expanded programme on immunization. A parish-level evaluation of the surveillance
      system.

PMID- 1390042
TI  - Foodborne clenbuterol poisoning.

PMID- 1390043
TI  - Trends in prostate cancer. 1980-1988.

PMID- 1390044
TI  - Migration and health. Health survey among Turkish residents.

PMID- 1390045
TI  - Tobacco or health. Tobacco mortality: present and future.

PMID- 1390046
TI  - Chemical safety. Study on the use and impact of pesticides.

PMID- 1390047
TI  - Dengue fever/dengue haemorrhagic fever surveillance. 1991.

PMID- 1390048
TI  - Cerebrospinal meningitis.

PMID- 1390049
TI  - Meningitis associated with measles-mumps-rubella vaccines.

PMID- 1390050
TI  - Diarrhoeal Disease Control Programme.

PMID- 1390051
TI  - Influenza.

PMID- 1390052
TI  - Noncommunicable diseases. Spina bifida incidence at birth.

PMID- 1390053
TI  - Progress in cardiovascular research during the last 2 decades (1971-1992).

PMID- 1390054
TI  - Immunization coverage survey.

PMID- 1390056
TI  - Sexually transmitted diseases in England in Wales 1990-1991.

PMID- 1390055
TI  - Epidemic of plague.

PMID- 1390057
TI  - Magnetic resonance imaging of the breast.
AB  - The diagnosis and treatment of breast cancer is dependent upon accurate depiction
      of the disease by diagnostic imaging. In a number of clinical situations,
      conventional breast imaging does not adequately address these diagnostic needs.
      New magnetic resonance imaging (MRI) methods developed specifically for breast
      diagnosis may provide the additional capability needed to fill the gap between
      clinical needs and the information obtained by conventional breast imaging
      methods. Fat-suppressed 3D MRI has demonstrated improved sensitivity over routine
      breast imaging methods. MRI can also be used to differentiate between certain
      benign but mammographically suspicious lesions and cancer. The potential clinical
      roles of MRI are reviewed with clinical examples. Pitfalls in the use of MRI are
      defined. The problems encountered with the implementation of MRI in a clinical
      setting are outlined and future advances predicted.

PMID- 1390058
TI  - Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'
      bis(phosphate): clinical experience with a new contrast agent.
AB  - Despite the many imaging techniques available to evaluate the liver, deficiencies
      persist. The choice of the optimal method is still controversial, with competing
      issues of safety, efficacy, and cost. Numerous strategies to improve the results
      of liver imaging have been pursued, including the application of tissue-targeted
      contrast agents to magnetic resonance imaging (MRI). Manganese (II) N,N'
      dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (Mn-DPDP) is one of
      several recently developed hepatobiliary agents, targeted to functioning
      hepatocytes. The Mn-DPDP-enhanced MRI has demonstrated promise in the clinical
      trials. Contrast-to-noise measurements have shown favorable results for Mn-DPDP
      enhanced MR compared to non-enhanced T1- and T2-weighted images. The ability to
      characterize tumors of hepatocellular origin and an improved capability for
      lesion detection have also been demonstrated. Furthermore, the prolonged
      enhancement obtained with Mn-DPDP has extended the time during which effective
      contrast is maintained. Importantly, no clinically significant adverse events
      have been demonstrated. This report will detail the clinical experience with Mn
      DPDP-enhanced MRI of the abdomen.

PMID- 1390059
TI  - Magnetic resonance imaging in the evaluation of cerebrospinal fluid flow
      abnormalities.
AB  - Phase contrast magnetic resonance imaging techniques can be used to evaluate the
      to-and-fro motion of cerebrospinal fluid (CSF) throughout the ventricles and
      subarachnoid space of the brain and spine. This CSF motion is due to transmitted
      cardiac pulsations from systolic expansion of the cerebral hemispheres. To cover
      the entire cardiac cycle, retrospective cardiac gating (rather than
      electrocardiographic triggering) must be used. Using this technique, it is
      possible to quantify CSF motion over a cardiac cycle and to distinguish normal
      aqueductal CSF "stroke volumes" from those seen in atrophy and shunt-responsive
      communicating hydrocephalus. Arachnoid cysts and other loculated CSF collections
      can be diagnosed using a "rebound sign" in which the motion of the CSF within the
      cyst is 90 degrees phase advanced over the CSF flowing around it.

PMID- 1390060
TI  - HIV infection mortality rates in Riverside males.

PMID- 1390061
TI  - Americans want more leadership on AIDS.

PMID- 1390062
TI  - Bosnia: working on the front line.

PMID- 1390063
TI  - Pay initiatives: nurses face a buyer's market.

PMID- 1390064
TI  - Health of the nation: conquering cancer.

PMID- 1390065
TI  - Who should teach nurses? The debate.

PMID- 1390066
TI  - Mental health: counselling sexual abuse survivors.
AB  - Some nurses are now becoming involved in helping adult survivors of child sexual
      abuse to overcome problems caused by an early abusive relationship. Developing a
      therapeutic partnership between victim and counsellor is a fundamental part of
      resolving such problems. Using a psychodynamic perspective, the author examines
      the effects of child sexual abuse on female survivors, and discusses the benefits
      of group therapy and individual counselling in helping the survivor to come to
      terms with the abuse.

PMID- 1390067
TI  - Testing renal patients for HIV: guidelines.
AB  - These guidelines for the testing of renal patients have been produced by the RCN
      Dialysis and Transplant Nurses Forum following a questionnaire sent to 61 renal
      units in the UK in 1988. Questions were asked relating to the current practice of
      testing patients for HIV within the renal population. The huge diversity of
      practice clearly demonstrated a fundamental lack of awareness of the ethical
      issues that are involved.

PMID- 1390069
TI  - Rehabilitation of muscle function. Part 1.
AB  - This article, which develops the concepts introduced in the authors' paper in
      last week's edition (1), is the first of two which review and summarise recent
      studies describing techniques to test the hypothesis that uniform frequency
      stimulation of skeletal muscle deprives the muscle of the type of signals that
      are necessary for rapid, appropriate and effective adaptation. Next week,
      clinical trials which have tested this hypothesis will be described, and the
      implications of the results for nurses involved in rehabilitation work discussed;
      Part 1 sets out the methodology of extracting the firing patterns of single motor
      units from a fatiguing muscle.

PMID- 1390068
TI  - An alternative to urinary conduit.
AB  - The author outlines the procedures involved in creating a Mitrofanoff pouch as an
      alternative to urinary conduit. Patients who have such a procedure must learn to
      alter their lifestyles and acquire skills such as self-catheterisation, but early
      results suggest that they find the procedure acceptable and preferable to other
      options.

PMID- 1390070
TI  - Trying to get your act together with a constantly changing script.

PMID- 1390071
TI  - Night shifts: light-headed night staff.

PMID- 1390072
TI  - Radiation: giving the nuclear all-clear.

PMID- 1390073
TI  - NHS reforms: punters sold down the river.

PMID- 1390074
TI  - Lateral nursing. Nursing: a boy's own world.

PMID- 1390075
TI  - Counselling: confronting the inevitable.

PMID- 1390076
TI  - Emergency nurses most fearful of HIV infection.

PMID- 1390078
TI  - Health of the nation: must try harder?

PMID- 1390077
TI  - Education: promoting the Jacuzzi model. Interview by Charlotte Alderman.

PMID- 1390079
TI  - Oncology: chemotherapy for elderly people.
AB  - Elderly people form a large proportion of cancer patients. This has implications
      for cancer care, in that age is a substantial risk factor in developing cancer.
      In spite of efforts to reduce cancer mortality through health education and
      screening, cancer rates are likely to increase in proportion to the ageing
      population. It has been suggested that health care professionals generally view
      elderly people in a negative fashion, which influences the care that these
      individuals receive. At present, there is a scarcity of information on the nature
      of cancer in elderly people, their tolerance to cytotoxic treatment, and specific
      age-related problems. Knowledge in all these areas remains fragmented and the
      research data conflicting. The nurse plays an important role in assessing and
      monitoring the impact of cytotoxic chemotherapy treatment. It is, therefore,
      imperative for cancer nurses to develop specialist knowledge in this area to
      enable them to understand the effect cytotoxic chemotherapy treatments have on
      elderly people.

PMID- 1390081
TI  - State of the unions in the Health Service.

PMID- 1390080
TI  - Aggression: therapeutic response to verbal abuse.
AB  - Increasing numbers of nurses in a variety of settings have to deal with physical
      and verbal aggression meted out by their patients. This article concentrates on
      suitable therapeutic responses to verbal abuse, and urges the nurse to consider
      aggression in a wider context, looking at the predisposing factors and methods to
      defuse potentially violent situations. The author stresses that self-evaluation
      is crucial if skills are to be learned and applied to subsequent episodes.

PMID- 1390082
TI  - Occupational health: developing safe handling policies.
AB  - This article is based on a paper given by the author at the Royal College of
      Nursing's Congress in April 1992, and is the first John Goodland Memorial
      Lecture. It examines the need for safe handling policies, and highlights the
      essential components of any new policy. With legislative changes due to come into
      force on December 31 1992, managers and staff are urged to be aware of the impact
      of safe handling training and how it can affect care delivery.

PMID- 1390083
TI  - Rehabilitation of muscle function. Part 2.
AB  - This article describes the utilisation of a physiologically based research
      technique developed to facilitate the nursing care of patients with skeletal
      muscle wasting. The technique, which involved electrotherapeutic stimulation to
      the first dorsal interosseous muscle of a group of arthritic patients,
      demonstrates that patterned neuromuscular stimulation of skeletal muscle can have
      enormously beneficial effects in preserving and regenerating skeletal muscle. The
      reasons for the muscle wasting, and the subsequent vicious spiral of immobility,
      were reviewed in Part 1 (1), and both articles build on the concepts described in
      a previous paper published in Nursing Standard (2).

PMID- 1390084
TI  - Doctors and nurses: named nurse does the rounds.

PMID- 1390085
TI  - Day in the life: Back to school nurses.

PMID- 1390086
TI  - The Clay column.

PMID- 1390087
TI  - Vienna Cancer Nursing Conference. Promoting the professional friend. Interview by
      Daniel Allen.

PMID- 1390088
TI  - Heading for the hills. Interview by Jackie O'Byrne.

PMID- 1390089
TI  - Whistleblowing: students at the sharp end.

PMID- 1390090
TI  - The health of the nation. A piecemeal approach to accident prevention.

PMID- 1390091
TI  - Occupational health: the nurse's role in workplace assessment.
AB  - In September 1991, the Health & Safety Executive (HSE) launched its biggest ever
      national awareness campaign relating to health at work. Called 'Lighten the
      Load', the campaign aims to raise awareness of work-related musculoskeletal
      disorders and encourage employers to reduce the frequency with which they occur.
      Occupational health nurses are ideally placed to play a major and active part in
      the campaign and assist in increasing awareness in both employers and the
      workforce.

PMID- 1390092
TI  - Mental health. Rehabilitation: a progressive approach.
AB  - For clients who have depended heavily on psychiatric services, or who have had
      lengthy admissions to hospital, the move to independent living can be a traumatic
      and difficult time if adequate support is not available. The author describes a
      rehabilitation unit for such clients, where staff aim to help them reach
      realistic decisions about their futures in a supportive environment.

PMID- 1390093
TI  - Nurse education in the Sultanate of Oman.
AB  - The quality of health care in the Sultanate of Oman has improved considerably
      over the past 20 years. Nurse education has developed accordingly with input from
      British nurses, many of whom leave the United Kingdom to work there every year.
      The author describes how nurse education has developed in the Sultanate and how,
      in spite of the influence and values of Western countries, the importance of the
      indigenous culture is not ignored.

PMID- 1390094
TI  - Whistleblowing: corresponding with truth.

PMID- 1390095
TI  - Mr Pink: management's story. Interview by Peter Milne.

PMID- 1390097
TI  - Learning disabilities nursing. Let's value each other.

PMID- 1390096
TI  - Lateral nursing: can the ideal become real?

PMID- 1390098
TI  - Learning disabilities nursing. Total quality in education.

PMID- 1390099
TI  - Learning disabilities nursing. Contracting for care.

PMID- 1390100
TI  - Learning disabilities nursing. Children and families first in short term care.

PMID- 1390101
TI  - Setting standards of care (continuing education credit).

PMID- 1390102
TI  - School nursing: more than bumps and bruises (continuing education credit).

PMID- 1390103
TI  - Acholeplasma multilocale sp. nov., isolated from a horse and a rabbit.
AB  - Acholeplasma strains were isolated from the nasopharynx of a horse (strain PN525T
      [T = type strain]) and the feces of a rabbit (strain B1). One clone of strain
      PN525T and one clone of strain B1 were examined in detail. These clones were
      indistinguishable from each other and were serologically distinct from the
      previously described Acholeplasma and Mycoplasma spp. The strains had the
      following properties: guanine-plus-cytosine content of 31 mol%; sterol was not
      required for growth, which occurred under both aerobic and anaerobic conditions;
      glucose was metabolized; and arginine was hydrolyzed. Strain PN525 (= NCTC 11723)
      is the type strain of a new species, Acholeplasma multilocale.

PMID- 1390104
TI  - Mycoplasma simbae sp. nov., Mycoplasma leopharyngis sp. nov., and Mycoplasma
      leocaptivus sp. nov., isolated from lions.
AB  - Mycoplasmas isolated from the throats of lions were shown to belong to three
      serotypes, all of which were serologically distinct from the previously
      recognized Mycoplasma and Acholeplasma spp. Eight mycoplasma colonies were
      cloned, including one from a leopard (strain LP), and were examined in detail for
      morphology, growth, and biochemical characteristics. The strains had the
      following properties: guanine-plus-cytosine contents of 37 mol% (strain LXT [T =
      type strain]), 28 mol% (strain LL2T), and 27 mol% (strain 3L2T) and a requirement
      for sterol. Strain 3L2T metabolized glucose, which was not metabolized by strains
      LXT and LL2T. Arginine and urea were not hydrolyzed. Strain LX (= NCTC 11724) is
      the type strain of a new species, Mycoplasma simbae; strain LL2 (= NCTC 11725) is
      the type strain of a second new species, Mycoplasma leopharyngis; and strain 3L2
      (= NCTC 11726) is the type strain of a third new species, Mycoplasma leocaptivus.

PMID- 1390106
TI  - Emended descriptions of Prevotella denticola, Prevotella loescheii, Prevotella
      veroralis, and Prevotella melaninogenica.
AB  - During studies of human periodontal disease, a number of bacterial strains were
      encountered that, on the basis of results of standard biochemical tests, appeared
      to be Prevotella buccalis, Prevotella denticola, Prevotella melaninogenica, or
      Prevotella loescheii. However, use of the standard biochemical tests, cellular
      fatty acid analyses, and the polyacrylamide gel electrophoresis patterns of
      soluble proteins resulted in conflicting identifications of these strains. The
      results of tests for cellobiose fermentation, inulin fermentation, and pigment
      production were responsible for most of the discordant results. Cellular fatty
      acid analyses in which the Microbial Identification System was used did not
      differentiate these strains from validly described species, even though separate
      library entries were created for them. DNA reassociation determinations in which
      the S1 nuclease procedure was used showed that cellobiose fermentation and
      pigment production are variable among strains of P. melaninogenica and P.
      denticola and that fermentation of xylan is not a reliable characteristic for
      differentiating P. buccalis from Prevotella veroralis. In contrast to previous
      indications, most strains of P. veroralis do not ferment xylan. These species can
      be differentiated by DNA-DNA reassociation and by cellular fatty acid analysis,
      using the Microbial Identification System, but differentiation by currently
      described phenotypic characteristics is not reliable. Similarly, P. loescheii and
      the genetically distinct (but closely related) D1C-20 group cannot be
      distinguished reliably from each other or from P. veroralis, P. denticola, and P.
      melaninogenica on the basis of currently described phenotypic tests other than
      cellular fatty acid composition or, for some species, electrophoretic patterns of
      soluble whole-cell proteins.

PMID- 1390105
TI  - Mycobacterium alvei sp. nov.
AB  - A new species of rapidly growing, nonphotochromogenic mycobacteria, Mycobacterium
      alvei, is described. The inclusion of this organism in the genus Mycobacterium is
      based on its acid fastness, its mycolate pattern, and its G + C content. A study
      of six strains showed that they form a homogeneous group with an internal
      phenotypic similarity value of 97 +/- 2.22%. DNA relatedness studies showed that
      the six M. alvei strains which we studied form a single DNA hybridization group
      which is less than 49% related to 14 other species of the genus Mycobacterium;
      the deltaTm values determined for the strains which exhibited higher levels of
      DNA homology were all greater than 7.9 degrees C. A lipid analysis showed that
      tuberculostearic acid was present. Docosanoic and tetracosanoic acid methyl
      esters were detected as mycolic acid cleavage products. All six isolates which we
      tested contained alpha-mycolic acids and relatively large amounts of a new kind
      of mycolic acid containing a methoxy group of omega-1 position, a characteristic
      that has not been described previously in mycobacteria. Strain CR-21 is the type
      strain; a culture of this strain has been deposited in the Collection Nationale
      de Cultures de Microorganismes de l'Institut Pasteur, Paris, France, as strain
      CIP 103464.

PMID- 1390108
TI  - Staphylococcus piscifermentans sp. nov., from fermented fish in Thailand.
AB  - New coagulase-negative staphylococci were isolated from fermented fish in
      Thailand. These organisms were differentiated from other Staphylococcus species
      on the basis of DNA relatedness and biochemical characteristics. Staphylococcus
      piscifermentans sp. nov. is described, and the type strain is strain SK03 (= NRIC
      1817 = JCM 6057 = TISTR 824).

PMID- 1390107
TI  - Biochemical and chemical studies on strains designated Prevotella intermedia and
      proposal of a new pigmented species, Prevotella nigrescens sp. nov.
AB  - A total of 31 strains of Prevotella intermedia were subjected to DNA-DNA
      hybridization and were characterized by performing physiological tests and by
      performing a multilocus enzyme analysis, using malate dehydrogenase and glutamate
      dehydrogenase. All of the strains assigned to P. intermedia fermented glucose and
      sucrose, hydrolyzed starch but not esculin, and produced indole, acetic,
      isobutyric, isovaleric, and succinic acids as metabolic end products. The results
      of DNA reassociation experiments performed with the reference probe permitted
      separation of the strains into two well-defined homology groups. In addition,
      strains with DNAs that hybridized with DNA from strain ATCC 25611T (T = type
      strain) had high levels of peptidase activity and cleaved lipid substrates (4
      methylumbelliferyl laurate and 4-methylumbellifelyl elaidate). Multilocus enzyme
      electrophoresis revealed two electromorphic profiles, one characteristic of
      strain ATCC 25611T and the other characteristic of strain ATCC 33563T. We propose
      that a new species, Prevotella nigrescens, should be created for the genetically
      distinct group of strains that hybridized with strain ATCC 33563T. Strain ATCC
      33563 is designated the type strain of P. nigrescens.

PMID- 1390109
TI  - Acholeplasma cavigenitalium sp. nov., isolated from the vagina of guinea pigs.
AB  - A mollicutes isolated from a guinea pig vagina was shown to be serologically
      distinct from previously recognized Mycoplasma and Acholeplasma species. Colonies
      isolated from 10 different guinea pigs were cloned and examined in detail. These
      strains were closely related and had the following properties: guanine-plus
      cytosine content of 36 mol%, no requirement for sterol, and aerobic growth.
      Glucose was not metabolized, and arginine and urea were not hydrolyzed. Strain
      GP3 (= NCTC 11727) is the type strain of a new species, Acholeplasma
      cavigenitalium.

PMID- 1390110
TI  - Relationships between members of the Mycoplasma mycoides cluster as shown by DNA
      probes and sequence analysis.
AB  - A gene probe, CAP-21, which demonstrated interrelationships between the members
      of the Mycoplasma mycoides cluster was developed. The probe easily differentiated
      mycoplasmas in this cluster by clear and predictable hybridization patterns in
      Southern blots and separated the cluster into four groups. Strains of M. mycoides
      subsp. mycoides which were capable of causing contagious bovine pleuropneumonia
      composed one group. Strains of M. mycoides subsp. mycoides which did not cause
      contagious bovine pleuropneumonia together with strains of M. mycoides subsp.
      capri composed the second group. Mycoplasma capricolum and the F38 mycoplasmas
      formed a third group, while the bovine group 7 mycoplasmas composed a separate,
      fourth group. Further support for the above grouping of the cluster was obtained
      when amplified DNA analogous to the probe from one representative strain of each
      of the cluster members was sequenced and these data were used to construct a
      phylogenic tree. Contagious caprine pleuropneumonia is recognized as an important
      disease, and the etiological agent of this disease is now known to be the F38
      mycoplasma. The CAP-21 probe did not differentiate between M. capricolum and the
      closely related F38 mycoplasma. A second probe, F38-12, which was capable of
      distinguishing these two mycoplasmas was made.

PMID- 1390111
TI  - Three new species of the genus Peptostreptococcus isolated from humans:
      Peptostreptococcus vaginalis sp. nov., Peptostreptococcus lacrimalis sp. nov.,
      and Peptostreptococcus lactolyticus sp. nov.
AB  - We describe three new species of the genus Peptostreptococcus which were isolated
      from human specimens and were tentatively identified as Peptostreptococcus
      prevotii. These three organisms were not homologous with previously described
      type strains of the genus Peptostreptococcus. A total of 12 strains that were
      identified biochemically as P. prevotii were divided into five independent DNA
      similarity groups; 10 of these strains were divided into three similarity groups
      which exhibited significant phenotypic differences from previously described
      species. Therefore, we propose the following new species: Peptostreptococcus
      vaginalis for group 1 strains, Peptostreptococcus lacrimalis for group 2 strains,
      and Peptostreptococcus lactolyticus for group 3 strains. The type strain of P.
      vaginalis is strain GIFU 12669 (= JCM 8138), the type strain of P. lacrimalis is
      strain GIFU 7667 (= JCM 8139), and the type strain of P. lactolyticus is strain
      GIFU 8586 (= JCM 8140).

PMID- 1390112
TI  - Recognition of Morganella subspecies, with proposal of Morganella morganii subsp.
      morganii subsp. nov. and Morganella morganii subsp. sibonii subsp. nov.
AB  - The genus name Morganella was established within the family Enterobacteriaceae in
      1978. Morganella morganii is the only species described thus far within this
      genus, and the name M. morganii has been accepted by usage in the scientific
      community for strains previously known as Proteus morganii. M. morganii isolates
      differ in their abilities to ferment trehalose and exhibit variable lysine and
      ornithine decarboxylase patterns, emphasizing the phenotypic heterogeneity within
      this species. Previous genetic studies failed to reveal separate entities within
      the genus Morganella. We observed some trehalose-fermenting strains with
      different lysine and ornithine decarboxylase patterns. Two strains were lysine
      and ornithine positive, 3 were lysine positive and ornithine negative, and 29
      were lysine negative and ornithine positive. These strains and 25 non-trehalose
      fermenting strains with different lysine and ornithine decarboxylase patterns
      were investigated. DNA-DNA hybridization studies and phenotypic characterizations
      revealed that M. morganii can be separated into three DNA relatedness groups and
      seven biogroups. Strains from DNA relatedness group 1 were trehalose negative,
      and strains from DNA relatedness groups 2 and 3 were trehalose positive. One
      biogroup from DNA relatedness group 2 was phenotypically indistinguishable from
      DNA relatedness group 3. On the basis of these studies, we propose that M.
      morganii be subdivided into M. morganii subsp. morganii (type strain ATCC 25830)
      containing biogroups A, B, C, and D (DNA relatedness group 1) and M. morganii
      subsp. sibonii (type strain 8103-85; = ATCC 49948) containing biogroups E, F, and
      G (DNA relatedness groups 2 and 3).

PMID- 1390113
TI  - Isolation and characterization of Shewanella alga from human clinical specimens
      and emendation of the description of S. alga Simidu et al., 1990, 335.
AB  - Genetic and phenotypic studies on the strains biochemically identified as
      Shewanella putrefaciens, which had a G+C content ranging from 52 to 54 mol% were
      conducted. The moles percent G+C of the type strain of S. putrefaciens is 46.
      Surprisingly, DNA homology experiments revealed that all these strains are
      genetically related to Shewanella alga (which was reported to produce
      tetrodotoxin), not to the type strain of S. putrefaciens. In this study, we
      reidentified clinical strains of S. putrefaciens which have a high range of moles
      percent G+C, as does S. alga. We also characterized the reidentified strains and
      found that the original description of S. alga (U. Simidu, K. Kita-Tsukamoto, T.
      Yasumoto, and M. Yotsu, Int. J. Syst. Bacteriol. 40:331-336, 1990) is
      insufficient to identify this strain. An emended description of S. alga is given.

PMID- 1390115
TI  - Correction of orthography of epithets in Pasteurella and some problems with
      recommendations on latinization.

PMID- 1390114
TI  - Identity of V factor in culture medium used for prior growth of two strains of
      Staphylococcus aureus.
AB  - Staphylococcus aureus ATCC 12598 and ATCC 25923 were starved of pyridine
      nucleotides and precursors and then grown in a semidefined medium containing
      [carbonyl-14C]nicotinamide. Samples of medium from late-exponential-phase and
      stationary-phase cultures were analyzed for 14C-metabolites. In all cases, V
      factor was present primarily as NAD.

PMID- 1390116
TI  - Variability of serum levels for three oral 8-methoxypsoralen brands.
AB  - We conducted a pilot study to investigate the serum level patterns of 3
      commercial and internationally introduced 8-methoxypsoralen (8-MOP) preparations
      in 9 patients for their bioequivalence and registered the interindividual
      variability of serum levels over 8 h after intake of 30 mg 8-MOP equivalent
      doses. On average, the highest serum levels (Cmax 120.1, range 235-61 ng.ml-1)
      were reached as early as 0.5-1 h after ingestion of Geroxalen soft gelatin
      capsules, whereas lower serum levels were seen after intake of the Oxsoralen hard
      gelatin capsules (Cmax 82.3, range 154-47 ng.ml-1) and the Mopsoralen tablets
      (Cmax 81.3, range 172-26 ng.ml-1). The importance of 8-MOP serum level
      determination for better and efficient PUVA therapy is discussed.

PMID- 1390117
TI  - Lunula change induced by psoralen plus ultraviolet A radiation.

PMID- 1390118
TI  - Ultraviolet B dose-dependent inflammation in humans: a reflectance spectroscopic
      and laser Doppler flowmetric study using topical pharmacologic antagonists on
      irradiated skin.
AB  - Normal skin responds acutely to ultraviolet (UV) light exposure with complex
      inflammatory mechanisms. In the present study UVB irradiation ranging from
      subclinical erythema doses to twice the minimal erythema dose (24 mJ/cm2 to 96
      mJ/cm2) was delivered to the skin of 8 volunteers. Pre-irradiated sites were
      immediately afterwards exposed to a 24-h occlusive patch containing 1 of 4 anti
      inflammatory agents or vehicle control. The resultant change in erythema
      (vascular reaction) was measured objectively using laser Doppler flowmetry (LDF)
      and reflectance spectroscopy (RS). The 4 anti-inflammatory compounds reduced the
      UVB-induced vascular reactions in different and dose-dependent ways.
      Betamethasone-17-valerate and diphenhydramine were most effective at the 24
      mJ/cm2 dose site and indomethacin and acetylsalicylic acid were more effective at
      sites > or = 48 mJ/cm2. Ranking the reduction in oxygenized hemoglobin (OH)
      content was as follows: betamethasone-17-valerate (OH reduction = 37.4%) >
      indomethacin (OH reduction = 21.5%) > acetylsalicylic acid (ASA) (OH decrease =
      21.0%) > diphenhydramine (OH reduction = 18.4%). Using LDF, the total ranking of
      the cutaneous blood flow (BF) reduction was: indomethacin (BF reduction = 39.7%)
      > betamethasone-17-valerate (BF reduction = 32.7%) > acetylsalicylic acid (BF
      decrease = 17.5%) > diphenhydramine (BF reduction = 12.3%). Diphenhydramine
      significantly reduced erythema only at the lowest irradiation dose (24 mJ/cm2)
      and the decrease in OH was associated with an increased amount of deoxygenized
      hemoglobin (DOH). A similar slight venous dilatation was present at
      acetylsalicylic acid-exposed sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390119
TI  - Immunomodulatory effects of AS101 on interleukin-2 production and T-lymphocyte
      function of lymphocytes treated with psoralens and ultraviolet A.
AB  - This study tested the immunomodulatory effects of AS101, a synthetic
      organotellurium compound, on interleukin (IL-2) production and functional
      activity of normal human lymphocytes. Normal human lymphocytes were treated in
      vitro with 8-methoxypsoralen alone, ultraviolet A (UVA) and psoralen plus UVA
      (PUVA) as well as with a combination of AS101 + phytohaemagglutinin (PHA)+phorbol
      myristate acetate (PMA) and the above-mentioned treatments. Following treatment
      IL-2 production, free IL-2 receptor (IL-2R), the ability of lymphocytes to induce
      a local graft-versus-host reaction (GVHR) and the ability of separated CD4 cells
      to induce help were tested. 8-Methoxypsoralen alone did not significantly affect
      either cell proliferation or IL-2 production or functional activity. However, UVA
      and PUVA had a high inhibitory effect on cell proliferation, IL-2 production, IL
      2R release and the functional activity of T- and T-helper lymphocytes. In the
      present study, the addition of AS101 and PMA serve to restore the impaired IL-2
      production, T- and T-helper lymphocyte functional activity, but not the IL-2R
      release. AS101 alone without PMA was also effective in restoring GVHR and helper
      activity of CD4 lymphocytes, without affecting cell proliferation.

PMID- 1390120
TI  - The relative importance of the components used for ultraviolet A protection in
      broad-spectrum sunscreens.
AB  - The need for effective ultraviolet A (UVA) protection is increasing. Broad
      spectrum sunscreens are being used to protect the skin against aging and in the
      treatment of photodermatoses, where UVA protection can be vital. They are also
      used by patients taking photosensitizing drugs, such as 8-methoxypsoralen, to
      protect their skin against solar UVA. This raises the question of what components
      in broad-spectrum sunscreens are the most necessary for optimal UVA protection.
      In the present study, the components that can be used are compared and evaluated
      using an animal method with the inhibition of skin edema induced by 8
      methoxypsoralen plus UVA as the biological end point. The results of this method
      indicate that powders do not provide any significant UVA protection. This could
      be due to the use of 8-methoxypsoralen in the test so that particularly the
      shorter UVA range is evaluated. Powders reflect mainly the longer UVA
      wavelengths. The UVA protection as measured with this method seems to be similar
      for the benzophenone derivative and for the dibenzoylmethane derivative. The UVA
      protection factors obtained are compared with those obtained in human skin using
      phototoxic erythema and UVA-induced tanning as parameters.

PMID- 1390121
TI  - Liquid formulations of 8-methoxypsoralen (8-MOP) and 5-MOP: a prospective double
      blind crossover assessment of acute non-phototoxic adverse effects.
AB  - Thirty-nine patients with psoriasis undergoing PUVA participated in a prospective
      double-blind study of acute non-phototoxic adverse effects comparing the liquid
      formulations of 8-methoxypsoralen (0.6 mg/kg) and 5-methoxypsoralen (1.2 mg/kg).
      A much higher number of patients experienced nausea (8-MOP = 51.3%, 5-MOP = 7.7%)
      and pruritus (8-MOP = 71.8%, 5-MOP = 43.6%) than has been reported for
      crystalline tablets. No attempt was made to compare therapeutic efficacy between
      liquid and crystalline tablet formulations or between 8-MOP and 5-MOP, which both
      appeared to be effective. The high incidence of adverse effects suggests that
      current dosage recommendations be reviewed.

PMID- 1390122
TI  - Influence of ultraviolet A on scheduled and unscheduled DNA synthesis by
      ultraviolet B.
AB  - After irradiating mouse epidermis in vivo with ultraviolet radiation (UV),
      autoradiography using 3H-thymidine was performed to study the effects of UV on
      scheduled and unscheduled DNA synthesis during a 7 day-period. Suppression of
      scheduled DNA synthesis by 100 mJ/cm2 of UVB was continued for about 24 h and
      induction of unscheduled DNA synthesis by 100 mJ/cm2 of UVB for about 6 h after
      irradiation. It was also confirmed that UVA induced DNA damage if a dose of UVA
      over 30 J/cm2 was used. When UVA was applied 1 h before UVB irradiation, a
      significant increase in sparsely labeled cells (SLC) was observed and the numbers
      of SLC increased in proportion to the total dosage of UV. So it was confirmed
      that UVA preirradiation enhanced DNA damage by UVB.

PMID- 1390123
TI  - Effect of psoralen and ultraviolet A on platelet functioning: an in vitro and in
      vivo study.
AB  - We investigated possible alterations induced by psoralen and ultraviolet A
      radiation (PUVA) on platelet function both in vitro and in vivo. In vitro, using
      conventional aggregometry and adenosine diphosphate (ADP), collagen, ristocetin
      and arachidonic acid as aggregating agents, platelet aggregation was determined
      on platelet-rich plasma (PRP) from normal subjects at basal conditions and
      following the addition of increasing concentrations of 8-methoxypsoralen (8-MOP)
      with and without exposure to ultraviolet A (UVA) light (5 J/cm2) and compared
      with UVA light exposure alone. At basal conditions and following exposure to UVA
      light alone, no changes in the normal platelet aggregation patterns were
      observed. Exposure to UVA light of PRP containing 8-MOP also demonstrated no
      abnormality in the platelet aggregation patterns at 8-MOP concentrations of 200
      ng/ml. However, abnormal platelet aggregation as a response to ADP and collagen
      was observed at higher concentrations of 8-MOP, which was augmented upon exposure
      to UVA light. In vivo, platelet aggregometry was performed on PRP from 4 patients
      submitted to PUVA treatment at basal conditions, 2.5 h after oral ingestion of 8
      MOP (0.6-0.8 mg/kg) and after 4 PUVA sessions. No patient showed modification of
      the platelet aggregation profile after either 8-MOP ingestion or PUVA treatment.
      Our study shows that 8-MOP at high concentrations in vitro impairs platelet
      aggregation by ADP and collagen augmented by UVA light exposure, but PUVA therapy
      causes no detectable abnormality in platelet function in vivo.

PMID- 1390124
TI  - Solar ultraviolet (UV) radiation and UV doses received by patients during four
      week climate therapy periods in the Canary Islands.
AB  - The ultraviolet (UV) radiation doses received by 270 psoriasis patients were
      studied during 4-week climate therapy periods in November, March or April in the
      Canary Islands. The daily total solar UV radiation (ambient radiation load, ARL)
      was measured using frequent readings with a Robertson-Berger sunburning
      ultraviolet (SUV) meter. A daily personal radiation load (PRL) was calculated for
      each patient, using sun exposure diary data. To measure the cumulative UV
      exposure of particular skin sites (skin site dose, SSD), 10 patients wore
      polysulphone UV dosimeters. The daily ambient radiation load (ARL) ranged from
      2.9 to 8.9 erythemal units (EU); the cumulative ARL for a 4-week treatment period
      was 182.6 EU. The mean daily personal radiation load (PRL), calculated separately
      for each week of the treatment period, was from 2.5 to 5.6 EU; the mean total 4
      week PRL was 118.0 EU, being about 65% of the ARL. The 4-week cumulative skin
      site dose (SSD) varied between 22.2 and 63.3% (mean 41.2%) of the corresponding
      personal radiation load (PRL).

PMID- 1390125
TI  - [Prompt aid from the air--also for premature infants].

PMID- 1390126
TI  - [How an intensive care nurse experiences the relationship with the preemie and
      and his parents].

PMID- 1390127
TI  - [General pre- and postoperative care].

PMID- 1390128
TI  - [A pediatric nurse in Iceland].

PMID- 1390129
TI  - [Meaningful environment-friendly disinfection and hygienic measures in
      pediatrics].

PMID- 1390130
TI  - [The role of fathers].

PMID- 1390131
TI  - [Poisonous and less poisonous plants. Part 3].

PMID- 1390132
TI  - [Johann Bokai, the father (1822-1884), and son (1858-1937)].

PMID- 1390133
TI  - [Inspection of medical documentation. Medical documentation has to show the
      complete course of the disease].

PMID- 1390134
TI  - [Independence of pediatric nursing].

PMID- 1390135
TI  - [Independence of pediatric nursing. How flexible is pediatric nursing?].

PMID- 1390136
TI  - The distribution of alpha 6 beta 4 integrins in lesional and non-lesional skin in
      bullous pemphigoid.
AB  - The alpha 6 beta 4 integrin is associated ultrastructurally with the
      hemidesmosomes of the basal keratinocytes and with the bullous pemphigoid antigen
      (BPA), suggesting an important role in adhesion of epidermal cells to the
      basement membrane. Using an immunofluorescence technique with chain-specific
      monoclonal antibodies to the alpha and beta subunits we have investigated the
      distribution of the alpha 6 beta 4 integrin in normal skin (n = 3) and in BP skin
      (uninvolved, perilesional and lesional) [n = 11]). The findings have been
      compared with other types of subepidermal blisters and with normal skin split by
      chemical means (n = 2) and by suction (n = 2). The distribution of alpha 6 beta 4
      integrin was compared with that of bullous pemphigoid antigen (BPA) and with
      other basement membrane zone (BMZ) macromolecules, laminin, collagen type IV,
      collagen type VII and the BM600 antigen. In uninvolved, perilesional and early
      pre-blistered lesional BP skin the distribution of both the alpha 6 and beta 4
      integrin subunits, BPA laminin, collagen types IV and VII and the BM600 antigen
      was identical to normal skin, i.e. a linear band in the BMZ. Within BP blisters,
      both alpha 6 and beta 4 integrin subunits and BPA were absent, except in two
      blisters in which the integrin expression was retained in the blister roof,
      despite loss of BPA. The other BMZ components were expressed on the blister
      floor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390137
TI  - Ultrastructural immunogold studies in two cases of linear IgA dermatosis. Are
      there two distinct types of this disease?
AB  - It has been suggested that patients with homogeneous linear IgA deposits at the
      basement membrane zone constitute a distinct bullous disorder called linear IgA
      dermatosis (LAD) of adults or children. The results of the present
      ultrastructural immunogold study in two patients with LAD suggest that LAD is not
      a single disease entity. LAD in a 10-year-old girl was found to be
      ultrastructurally similar to an IgA-type pemphigoid. IgA was detected in the
      uppermost lamina lucida underlying the basal cell plasma membrane. In a second
      patient, an 86-year-old man, IgA deposits were present within the lamina densa
      and the anchoring plaques. The distribution of IgA in this patient was
      ultrastructurally identical with that of IgG in epidermolysis bullosa acquisita
      skin and with that of the non-collagenous globular terminus of collagen VII
      within the basement membrane zone of normal skin. By using the immunogold
      technique, we could distinguish two distinct types of LAD according to the IgA
      binding sites in the diseased skin. We suggest that different labelling patterns
      may correspond to different clinical pictures.

PMID- 1390138
TI  - Failure to demonstrate the true resection margins of excised skin tumours: a case
      for routine marking.
AB  - A solution of silver nitrate in methanol was used to assess the demonstration of
      the true surgical excision margin at histology of 100 skin excisions for basal
      cell carcinoma. In 15% of cases the true margin was not presented and deeper
      sections were required. The findings highlight the need for routine marking of
      excision specimens of neoplastic skin lesions to prevent incorrect diagnosis of
      incomplete excision based on a false resection margin.

PMID- 1390139
TI  - Dynamic hepatic scintigraphy in the screening of psoriatic patients for
      methotrexate-induced hepatotoxicity.
AB  - We report the use of dynamic hepatic scintigraphy in the assessment of the
      hepatic status of psoriatic patients before and during methotrexate therapy.
      Eighty-seven paired dynamic scans and percutaneous liver biopsies were performed
      in 63 patients. The liver biopsies were graded according to Warin et al. with
      fibrosis of grade 2 or worse being a strong indication for withdrawal of
      methotrexate. The sensitivity of dynamic hepatic scintigraphy in detecting
      fibrosis of grade 2 or worse was 83.3% and the specificity was 81.5%. The
      predictive value of a normal scan for fibrosis of grade 0-1 was high (98.5%)
      although the predictive value of an abnormal scan for fibrosis of grade 2 or
      worse was low (25%). Dynamic hepatic scintigraphy may therefore offer a means to
      reduce the number of liver biopsies necessary in patients receiving methotrexate
      for psoriasis.

PMID- 1390140
TI  - The phenotype of Darier's disease: penetrance and expressivity in adults and
      children.
AB  - The prevalence, pattern of inheritance, and phenotype of Darier's disease was
      examined in a cross-sectional study of cases in north-east England. Seventy-five
      cases, representing a local prevalence of at least 1:36,000, were identified and
      examined. Forty-two cases were known to dermatologists, and 33 were identified in
      the course of the study: 60 were adults (above the age of 20) and 15 were
      children. In nine families, 66 of 136 adults with an affected parent were known
      to be affected, indicating complete penetrance of an autosomal dominant gene.
      eighteen individuals gave no family history, but seven of these were found to be
      members of affected kindreds and five obligate carriers examined all proved to
      have evidence of the disease. In other 'new' cases, including several whose
      parents were examined and confirmed to be normal, no relationship to other cases
      was found. These cases probably represent new mutations or non-paternity rather
      than incomplete penetrance. All but one adult case had the typical rash, but it
      was milder in women; 16/18 adults who had not presented to dermatologists were
      female. Diagnostic nail lesions were found in 59 (99%), palmar pits and keratoses
      in 57 (95%), and acrokeratosis verruciformis in 44 (73%). In 15 young cases (aged
      5-18) with one or more diagnostic features, the rash was found in only four
      (27%), nail lesions in nine (60%), palmar pits in eight (53%), and acrokeratoses
      in ten (67%). The minor lesions were often subtle but were more consistent early
      evidence of disease than the rash, and even in the absence of a rash gene
      penetrance may be complete by the age of 10.

PMID- 1390141
TI  - The influence of daily dish-washing with synthetic detergent on human skin.
AB  - The effects of regular dish-washing on the stratum corneum barrier function, as
      determined by transepidermal water loss (TEWL), and objective and subjective skin
      parameters, were investigated in a 'use test' performed by 18 healthy volunteers.
      Hands were soaked in a 0.05% solution of a commercial dish-washing product (three
      times/day, for 15 min, at 37 degrees C) over a period of 3 weeks; one hand was
      unprotected and the other was protected with a commercial rubber glove. TEWL
      increased in 13/18 volunteers by more than 25% above baseline on exposed hands
      within the first 2 weeks of the study. Objective skin signs (erythema, scaling,
      fissures) and subjective symptoms (itching, dryness, smarting) occurred almost
      exclusively in subjects with substantial TEWL increases and were most prominent 1
      2 weeks following peak TEWL values. There was a highly significant correlation
      between cumulative relative symptom scores and TEWL changes. TEWL increase and
      symptom scores were not correlated with a history of inhalant allergy and/or
      elevated serum IgE levels. Three volunteers, who had shown the highest increase
      of TEWL values and the most intense clinical reactions to the detergent were
      subjected to a control experiment in which one hand was soaked in warm tap-water
      following the same experimental protocol. No significant effects on TEWL values
      or skin symptoms were observed. We conclude that regular exposure to low
      concentrations of detergents as used for dish-washing is capable of inducing skin
      lesions in a substantial proportion of individuals.

PMID- 1390142
TI  - Cutaneous manifestations of the eosinophilia-myalgia syndrome.
AB  - We report the cutaneous manifestations of the eosinophilia-myalgia syndrome in 10
      patients, with specific reference to their clinical course, histopathological
      features, and immunogenetic studies. Cutaneous manifestations could be classified
      into three groups: morphoea-like sclerosis, urticarial and papular lesions, and
      generalized sclerosis. Despite this polymorphic clinical presentation, the
      histopathological abnormalities in all cases were strikingly similar, and
      consisted of superficial and deep perivascular lymphocytic dermal infiltrates,
      mucin deposition, and fascial inflammation (often in the absence of sclerosis).
      Immunoperoxidase studies revealed increased numbers of factor XIIIa- and MAC 387
      positive cells in the inflammatory infiltrate. Immunogenetic studies demonstrated
      that 77% (7/9) of patients possessed the HLA-DR3 or HLA-DR4 phenotypes. Mean
      follow-up of 24 months after discontinuation of L-tryptophan revealed the
      presence of persistent severe disabling disease in 30% of patients.

PMID- 1390143
TI  - A portable pulsed electromagnetic field (PEMF) device to enhance healing of
      recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.
AB  - A prospective, randomized, double-blind, placebo-controlled multicentre study
      assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer
      therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers.
      The portable device was used at home for 3 h daily during this 8-week clinical
      trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain
      intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a
      47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P <
      0.0002). Investigators' global evaluations indicated that 50% of the ulcers in
      the active group healed or markedly improved vs. 0% in the placebo group, and 0%
      of the active group worsened vs. 54% of the placebo group (P < 0.001).
      Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04)
      favouring the active group were seen. Patients whose ulcers improved
      significantly after 8 weeks were permitted to continue double-blind therapy for
      an additional 4 weeks. Eleven active and one placebo patient continued therapy
      until week 12, with the active treatment group continuing to show improvement.
      There were no reports of adverse events attributable to this device. We conclude
      that the PELUT device is a safe and effective adjunct to non-surgical therapy for
      recalcitrant venous leg ulcers.

PMID- 1390144
TI  - Roxithromycin versus penicillin in the treatment of erysipelas in adults: a
      comparative study.
AB  - A prospective, randomized, multicentre trial was conducted to evaluate the
      efficacy and safety of roxithromycin (150 mg b.i.d. orally) and penicillin (2.5
      MU x 8 daily intravenously, then 6 MU daily orally) in the treatment of
      hospitalized adult patients with erysipelas. Seventy-two patients entered the
      study. Thirty-one patients in the roxithromycin group and 38 patients in the
      penicillin group completed the trial. The overall efficacy rates (cure without
      additional antibiotics) were 84% (26/31) in the roxithromycin group and 76%
      (29/38) in the penicillin group (P = 0.43). No side-effects were observed in the
      roxithromycin-treated patients whereas rashes occurred in two cases in the
      penicillin group, leading to exclusion from the study. Oral roxithromycin can
      thus be considered an effective and well-tolerated treatment for erysipelas in
      adult hospitalized patients.

PMID- 1390146
TI  - Extensive and fatal basal cell carcinoma: a report of three cases.
AB  - Three cases of basal cell carcinoma (BCC) with extensive invasion are described.
      The first two patients had meningeal and cerebral involvement with exposure of
      their dural meninges following full thickness skull erosion. The third patient
      had bilateral orbital and optic nerve involvement resulting in complete
      blindness. All three patients subsequently died from their disease.

PMID- 1390145
TI  - Multifocal aplasia cutis congenita, distal limb hemimelia, and cutis marmorata
      telangiectatica in a patient with Adams-Oliver syndrome.

PMID- 1390147
TI  - An acantholytic dyskeratotic epidermal naevus with other features of Darier's
      disease on the same side of the body.
AB  - Many epidermal naevi with the histology of Darier's disease have been reported.
      In the absence of associated features of Darier's disease, they cannot be assumed
      to have a common pathogenesis with it, and it has been suggested that they are
      better classified as acantholytic dyskeratotic epidermal naevi rather than
      naevoid Darier's disease. We describe a patient with such a naevus who had
      typical nail and palmar changes of Darier's disease on the same side of the body.
      We suggest that in at least some cases the naevus has the same genetic defect(s)
      as generalized Darier's disease, and discuss the possibility that a patient with
      such a naevus could occasionally transmit Darier's disease to an offspring.

PMID- 1390148
TI  - Epidermolysis bullosa acquisita with oesophageal stenosis.
AB  - Epidermolysis bullosa acquisita (EBA) is a rare acquired subepidermal blistering
      disorder associated with autoimmunity to type VII collagen. Although the full
      clinical spectrum of EBA is still being defined, it is now known that EBA has
      greater clinical heterogeneity than previously suggested. We describe a patient
      with EBA which closely approximated the severity of the recessive form of
      dystrophic epidermolysis bullosa.

PMID- 1390149
TI  - Multiple xanthogranulomas in an adult: case report and literature review.
AB  - An otherwise healthy 30-year-old male developed multiple xanthogranulomas over a
      1-year period. A review of the literature on adult xanthogranulomas and a
      tabulated outline of the differential diagnosis is presented.

PMID- 1390150
TI  - Cutaneous granulocytic sarcoma (chloroma) presenting as the first sign of relapse
      following autologous bone marrow transplantation for acute myeloid leukaemia.
AB  - A 25-year-old man suffering from acute myeloid leukaemia developed a solitary
      lesion on the upper abdominal wall 6 months after receiving an autologous bone
      marrow transplant. The lesion was a chloroma and proved to be the only evidence
      of clinical relapse. This is the first reported case of this rare condition
      occurring following bone marrow transplantation.

PMID- 1390151
TI  - Correlation between the pretreatment number of blisters and the time to control
      bullous pemphigoid with prednisone 1 mg/kg/day.

PMID- 1390152
TI  - Exacerbation of bleeding tendency in a patient with haemophilia A during
      treatment with isotretinoin.

PMID- 1390153
TI  - Generalized pustular psoriasis associated with bacterial endocarditis of the
      anterior papillary muscle.

PMID- 1390154
TI  - Facial oedema and acne vulgaris.

PMID- 1390155
TI  - A theoretical model of the blanching response after copper vapour laser treatment
      of telangiectasia.

PMID- 1390156
TI  - Acitretin in the treatment of mal de Meleda.

PMID- 1390157
TI  - Familial multiple pilomatrixomas.

PMID- 1390158
TI  - Branchial cyst of the neck.

PMID- 1390159
TI  - Vitamin D analogues and psoriasis.
AB  - Topical vitamin D analogues offer a new, effective, more convenient and generally
      well-tolerated option for the treatment of psoriasis. Only psoriasis vulgaris has
      been intensively studied, but other forms of the disease may also respond. Both
      calcitriol and calcipotriol have been shown to be effective in numerous clinical
      trials, and the latter has compared well with betamethasone valerate and short
      contact dithranol in controlled studies. Their mechanism of action is not yet
      fully understood and may prove complex. The most important effect may be a direct
      regulation of keratinocyte proliferation and differentiation. However, these
      compounds also have potent immunological properties, and may act by inhibition of
      cytokine production by keratinocytes or lymphocytes. Topical application of
      vitamin D analogues appears generally to be remarkably safe, but hypercalcaemia
      and hypercalciuria may develop if large quantities are used.

PMID- 1390160
TI  - Quantification of n-alkanes in stratum corneum in the hereditary ichthyoses.
AB  - Chromatographic assay of n-alkanes in skin showed detectable levels in normal
      controls and in patients with various forms of hereditary ichthyosis. Raised n
      alkanes were found in some, but not all, patients with non-bullous and bullous
      ichthyosiform erythroderma and in individual patients with lamellar ichthyosis,
      ichthyosis vulgaris and Netherton's syndrome. The finding of elevated scale n
      alkanes is neither consistent in ichthyosis, nor specific to any one type of
      ichthyosis, and n-alkane assay is not helpful in distinguishing one type of
      hereditary ichthyosis from another. The source of n-alkanes in ichthyotic scale
      and their role, if any, in the pathogenesis of ichthyosis remain obscure.

PMID- 1390161
TI  - Measurement of phosphoinositide-specific phospholipase C activity in mononuclear
      leucocytes from atopic and normal subjects.
AB  - The intracellular inositol pathway is an important route for cell activation and
      relies on the stimulation of membrane-bound phosphoinositide-specific
      phospholipase C (PLC). Previously we have shown abnormalities of inositol
      metabolism in mononuclear cells (MNL) in atopic dermatitis (AD) using an indirect
      method. We now describe a direct method of measuring PLC activity in membrane and
      cytosol preparations of MNL in AD. We compare PLC activity in AD with that in
      normal controls and examine the effect of substrate concentration and nucleotide
      stimulation on the system. Our findings show increased membrane-bound PLC
      activity in AD compared with normal controls. Non-specific stimulation of AD PLC
      activity by nucleotides suggests that the enzyme of atopics is more sensitive to
      substrate-driven activity than that of non-atopics.

PMID- 1390162
TI  - Churg-Strauss syndrome.

PMID- 1390163
TI  - Family history, smoking habits, alcohol consumption and risk of psoriasis.
AB  - We have conducted a multicentre case-control study to assess the epidemiological
      importance of previously suggested risk factors for psoriasis, including family
      history of the disease, smoking and alcohol consumption. Newly diagnosed
      psoriatics, with a history of skin manifestations no longer than 2 years were
      eligible as cases; as controls we selected subjects with newly diagnosed
      dermatological conditions other than psoriasis. Interviews were performed by
      trained medical investigators using a structured questionnaire. Two-hundred and
      fifteen cases, aged 16-65 years (median age 38), and 267 controls, aged 15-65
      years (median age 36), were interviewed and included in the analysis. Family
      history was a risk factor for psoriasis; the multiple logistic regression (MLR)
      adjusted-odds ratio was 18.8 (95% confidence interval 6.4-54.8) for a history in
      parents, and 3.2 (95% confidence interval 1.5-6.6) for a history in siblings. The
      risk of psoriasis was higher for current smokers than for those who had never
      smoked. The MLR adjusted odds ratio was 2.1 (95% confidence interval 1.1-4.0) for
      people smoking 15 cigarettes or more per day. The risk of psoriasis was higher
      for alcohol drinkers: compared with teetotallers the MLR adjusted-odds ratios
      were 1.3 (95% confidence interval 0.8-2.3) for subjects drinking one or two
      drinks/day and 1.6 (95% confidence interval 0.9 to 3.0) for those drinking three
      or more. However, the trend in risk was not statistically significant. Our study
      confirms the role of family history in psoriasis and provides some evidence of a
      dose-response relationship for an association between smoking habits and
      psoriasis.

PMID- 1390164
TI  - No evidence for a spirochaetal origin of localized scleroderma.
AB  - We looked for evidence of a Borrelia infection in 15 patients with morphoea. We
      were not able to detect antibodies to Borrelia burgdorferi in any of these 15
      patients. None of the 14 skin biopsies examined by immunohistochemistry showed
      evidence of spirochaetes. Skin biopsies were cultured in 10 patients. All were
      negative. These results do not support a spirochaetal origin of localized
      scleroderma.

PMID- 1390165
TI  - Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of
      atopics.
AB  - A characteristic feature of non-eczematous atopic dry skin (DS) appears to be an
      impaired water permeability barrier (WPB) function. The WPB is constituted by
      intercellular lipid lamellae, located between the horny cells of the stratum
      corneum (SC), which are provided by exocytosis of lamellar bodies (LB). The aim
      of this study was to elucidate whether alterations in the dynamics of LB
      extrusion could be responsible for this WPB disturbance. In an ultrastructural
      morphometric comparison the relative volume of LB in the two uppermost subcorneal
      layers in DS of atopics (n = 9) and healthy skin of controls (n = 7) was
      determined. The LBs were differentiated into extracytoplasmic LB, i.e. with the
      cell membrane already fused, and intracytoplasmic LB, i.e. entirely located
      within the cell. The total volume in the two cell layers of the stratum
      granulosum did not differ between atopics and controls. However, separate
      evaluation of the two LB-compartments revealed statistically significant
      differences between atopics and healthy controls. In the second uppermost cell
      layer of the stratum granulosum only 13% of the total LB volume of this layer had
      already fused with the cell membrane in the atopics as opposed to 42% in the
      controls. On the other hand more LB remained undelivered within the cells of the
      uppermost SG cell layer of the atopics (26% in atopics versus 8% in controls, P <
      0.01). These findings suggest that a pathological extruding mechanism of LB in DS
      may be at least partly responsible for the recently detected biochemical
      alterations of epidermal lipids, and for the deficient WPB.

PMID- 1390166
TI  - Selective activation of circulating CD4+ lymphocytes in severe adult atopic
      dermatitis.
AB  - An analysis of peripheral blood lymphocyte subsets and their expression of
      activation markers was performed using flow cytometry in 12 adult patients with
      severe atopic dermatitis, and compared with 14 normal individuals. Repeated
      measurements were made over an 8-week period during which disease activity was
      also assessed. Increased percentages of activated and unactivated CD4+
      lymphocytes, and decreased percentages of CD8+ cells were observed in atopic
      dermatitis. Increasing disease activity was associated with an increase in the
      proportion of activated and unactivated CD4+ lymphocytes and a fall in the
      proportion of CD8+ cells. This study demonstrates that in adults with severe
      atopic dermatitis, increasing disease activity is associated with selective
      activation of CD4+ lymphocytes and a relative expansion of the CD4+ cell subset.

PMID- 1390167
TI  - Possible mechanisms of immune modulation in chronic dermatophytoses: an in vitro
      study.
AB  - It has been suggested that patients with chronic superficial Trichophyton rubrum
      infection have defective cellular immunity to dermatophyte antigens. This may be
      due to a selective anergy to dermatophyte antigens or reflect the activity of
      dermatophyte-derived lymphocyte inhibitory factors. To explore these
      possibilities, we assessed lymphocyte transformation to a variety of recall
      antigens, including a cytoplasmic and exoantigen preparation of Trichophyton
      rubrum in 15 patients with chronic dermatophyte infection and 15 age- and sex
      matched positive controls. In a duplicate set of experiments, autologous serum
      was replaced by heat-inactivated fetal calf serum. In addition, the direct effect
      of Trichophyton rubrum extracts on lymphoproliferation was assessed in vitro.
      Comparable lymphocyte transformation to each recall antigen was observed in
      patients and controls. Moreover, we found no evidence for a circulating
      dermatophyte-derived lymphocyte inhibitory factor in sera from patients with
      chronic superficial infection. A direct inhibitory effect of Trichophyton rubrum
      on lymphocyte proliferation to recall antigens was observed, however, at protein
      concentrations of > 10 micrograms/ml (exoantigen preparation) and > 25
      micrograms/ml (cytoplasmic preparation). This inhibitory effect was rapidly
      reversible, not associated with loss of cell viability and maximal when added
      within 24 h of antigen to cultured lymphocytes. Class II MHC antigen HLA-DR, a
      surface marker of T-cell activation, was observed on inhibited lymphocytes co
      cultured with antigen, suggesting the primary target for the inhibitory effect in
      vitro is the lymphocyte rather than the antigen-presenting cell.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390168
TI  - Characterization of inflammatory infiltrates in male pattern alopecia:
      implications for pathogenesis.
AB  - Hair-bearing, transitional, and alopecic scalp from three males and one female
      with progressive pattern alopecia were examined. Ultrastructural studies
      disclosed measurable thickening of the follicular adventitial sheaths of
      transitional and alopecic zones compared with those in the non-alopecic zones.
      This finding was associated with mast cell degranulation and fibroblast
      activation within the fibrous sheaths. Immunohistochemically, control biopsies
      were devoid of follicular inflammation (n = 3), while transitional regions
      consistently showed the presence of activated T-cell infiltrates about the lower
      portions of follicular infundibula. These infiltrates were associated with the
      induction of class II antigens on the endothelial linings of venules within
      follicular adventitia and with apparent hyperplasia of follicular dendritic cells
      displaying the CD1 epitope. Inflammatory cells infiltrated the region of the
      follicular bulge, the putative source of stem cells in cycling follicles. The
      data suggest that progressive fibrosis of the perifollicular sheath occurs in
      lesions of pattern alopecia, and may begin with T-cell infiltration of follicular
      stem cell epithelium. Injury to follicular stem cell epithelium and/or thickening
      of adventitial sheaths may impair normal pilar cycling and result in hair loss.

PMID- 1390169
TI  - Topical vitamin C protects porcine skin from ultraviolet radiation-induced
      damage.
AB  - Ultraviolet radiation damage to the skin is due, in part, to the generation of
      reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co
      factor and antioxidant due to its reducing properties. Topical application of
      vitamin C has been shown to elevate significantly cutaneous levels of this
      vitamin in pigs, and this correlates with protection of the skin from UVB damage
      as measured by erythema and sunburn cell formation. This protection is biological
      and due to the reducing properties of the molecule. Further, we provide evidence
      that the vitamin C levels of the skin can be severely depleted after UV
      irradiation, which would lower this organ's innate protective mechanism as well
      as leaving it at risk of impaired healing after photoinduced damage. In addition,
      vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and
      therefore shows promise as a broad-spectrum photoprotectant.

PMID- 1390170
TI  - Increased levels of inflammatory cytokines in human skin lymph derived from
      sodium lauryl sulphate-induced contact dermatitis.
AB  - A superficial peripheral lymph vessel draining the skin of the upper and medial
      part of the foot was cannulated on the lower leg of six healthy human volunteers.
      After 2 days an irritant contact dermatitis was induced by application of 10%
      sodium lauryl sulphate to the area of skin drained by the lymph vessel. Three
      days later the spontaneously regressing skin reaction was treated with clobetasol
      propionate. Lymph was collected twice daily for 7 days, and the levels of various
      cytokines (IL-1 alpha, IL-1 beta, IL-2 and soluble IL-2 receptors, IL-6, IL-8,
      TNF-alpha, GM-CSF) were determined by ELISA technique. In the majority of the
      volunteers all cytokines examined were detected in several lymph samples, with
      the exception of IL-1 alpha and IL-8. In parallel with the clinical symptoms of
      the contact dermatitis the levels of IL-6 and TNF-alpha increased 8-10-fold,
      whereas for IL-1 beta, IL-2, IL-2 receptors, and GM-CSF there was a delayed, 2-3
      fold increase. These results suggest that cytokines, in particular IL-6 and TNF
      alpha, may actively participate in the immunological reactions in the skin and in
      the regional lymph nodes during contact dermatitis.

PMID- 1390171
TI  - A multicentre, parallel-group comparison of calcipotriol ointment and short
      contact dithranol therapy in chronic plaque psoriasis.
AB  - Short-contact treatment with dithranol (anthralin) is a widely used treatment for
      chronic plaque psoriasis. Although effective, it causes staining and irritation,
      and is therefore inconvenient. Calcipotriol is a recently developed vitamin D
      analogue which is effective and easy to use. To evaluate the relative efficacy,
      safety and acceptability of these treatments a multicentre, open, randomized,
      parallel-group comparison was performed. Four hundred and seventy-eight patients
      with chronic plaque psoriasis were randomized to use one of the two treatments
      for 8 weeks. One group applied calcipotriol ointment (50 micrograms/g) twice
      daily. The other used a single application for 30 min each day of Dithrocream in
      the highest concentration tolerated. Severity of psoriasis was assessed by
      modified PASI score at baseline, and after 2, 4, and 8 weeks of treatment. A five
      point scale was used by subjects and by investigators as an additional assessment
      of overall response, and a similar scale was used by subjects to grade
      acceptability. Total serum calcium was monitored at baseline and after 2 and 8
      weeks on treatment. The mean PASI score fell from 9.1 to 4.7 after 8 weeks on
      dithranol (P < 0.001), and from 9.4 to 3.4 on calcipotriol (P < 0.001). The
      difference between the two treatments was significant in favour of calcipotriol
      at 2 weeks (P < 0.001), and remained so at subsequent assessments. At 8 weeks the
      difference between mean improvements in scores for the two groups was 1.6 (95%
      confidence interval 0.5-2.7). Efficacy grading by subjects and investigators, and
      acceptability grading by subjects, were all significantly better for
      calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390173
TI  - Dyskeratosis congenita: delay in diagnosis and successful treatment of
      pancytopenia by bone marrow transplantation.
AB  - Dyskeratosis congenita is an inherited disorder characterized by nail dystrophy,
      skin pigmentary changes, mucosal leukoplakia, pancytopenia and an increased
      incidence of malignancy. Because of a widely held view that the outcome of bone
      marrow transplantation in dyskeratosis congenita is poor, this treatment option
      is sometimes not considered when pancytopenia develops. We present a child
      currently doing well 3 years after bone marrow transplantation, and review the
      literature.

PMID- 1390172
TI  - Enhanced association of plasminogen/plasmin with lesional epidermis of bullous
      pemphigoid.
AB  - The distribution of plasminogen/plasmin, the central proteolytic component of the
      plasminogen activator/plasmin system was analysed in lesional skin of bullous
      pemphigoid by using monoclonal antibodies (MAbs) specific for distinct epitopes
      of the plasminogen/plasmin molecule. Four groups of MAbs were used: (i) MAbs HD
      PG 1 and HD-PG 2, specific for epitopes associated with the lysine-binding sites
      I (kringle domain 1 + 2 + 3) and II (kringle domain 4) of plasminogen/plasmin,
      (ii) MAbs HD-PG 6 and HD-PG 7, specific for the lysine binding site I only, (iii)
      MAbs HD-PG 12 (formerly designated P 2) and HD-PG 18, specific for non-kringle
      domains of glu- and lys-plasminogen, and (iv) MAb HD-PG 13 which recognizes glu
      plasminogen, only. The basal cell layers of normal skin consistently reacted with
      MAb HD-PG 12, whereas only faint staining was seen with the other MAbs in the
      same biopsies. In contrast, all anti-plasminogen/plasmin MAbs strongly stained
      lower and intermediate epidermal cell layers of fully developed bullous
      pemphigoid lesions.

PMID- 1390174
TI  - Granulomatous hypersensitivity to protamine as a complication of insulin therapy.
AB  - A patient is described who developed a granulomatous skin reaction to injections
      of protamine-insulin for the treatment of her diabetes mellitus. By means of skin
      testing it was shown that this reaction was caused by protamine. No adverse
      effects were seen when she was injected with insulin which did not contain
      protamine.

PMID- 1390175
TI  - Pemphigus vegetans in a child.
AB  - Pemphigus vegetans was diagnosed in a 12-year-old boy based on clinical,
      histopathological and immunohistological findings. To our knowledge, this is the
      first case of juvenile pemphigus vegetans to be published in the literature.
      Suggested treatment with prednisone and azathioprine was refused, and the patient
      was treated with a decoction of herbs prescribed by a practitioner of traditional
      Chinese herbal medicine. This treatment gave excellent results. Possible active
      components of the treatment are discussed.

PMID- 1390176
TI  - Verapamil-induced secondary erythermalgia.
AB  - A 59-year-old man developed red, swollen and warm feet accompanied by
      intermittent burning pain during treatment for cardiac failure and arrhythmias
      with several drugs including verapamil. The condition gradually worsened until
      there was persistent disabling burning pain and severe erythema and swelling of
      the feet. Aspirin and other analgesics were ineffective in relieving the
      discomfort. Histopathology of punch biopsies showed a mild perivascular
      mononuclear infiltrate and moderate perivascular oedema. Within 2 weeks of
      stopping verapamil the burning pain, erythema, and swelling of the feet had
      resolved. The clinical features and subsequent course are consistent with a
      diagnosis of erythermalgia secondary to verapamil.

PMID- 1390177
TI  - White fibrous papulosis of the neck.
AB  - We report two middle-aged women who presented with multiple, discrete, non
      follicular, oval, pale, asymptomatic lesions on the neck. Clinical and
      histopathological features were compatible with the entity of white fibrous
      papulosis of the neck.

PMID- 1390178
TI  - Diagnostic phototesting in the United Kingdom. British Photodermatology Group.

PMID- 1390180
TI  - Visual impairment secondary to rosacea.

PMID- 1390179
TI  - Relapsing polychondritis--treatment with cyclosporin A.

PMID- 1390181
TI  - Retinoids and photodamage.
AB  - Extensive well-controlled clinical studies performed over the past 5 years have
      demonstrated a consistent, dose-dependent, statistically significant improvement
      in the appearance of photodamaged skin after 3-6 months of daily treatment with
      topical 0.001-0.1% tretinoin cream. Clinical changes included decreases in
      surface roughness, irregular pigmentation, fine and coarse wrinkling, and
      sallowness. Actinic keratoses have also been reported to decrease in size and
      number. Blinded analysis of biopsies from more than 500 subjects showed that
      there was compaction of the stratum corneum, an increase in the number of
      granular layers, thickening of the epidermis and a decrease in epidermal melanin.
      There were no detectable histological changes in any dermal parameters. The
      specific cellular mechanisms by which retinoic acid (RA) exerts its beneficial
      effect on photodamaged skin are currently the subject of intensive investigation.
      It is well established that RA enters the nucleus where it binds to an RA
      receptor (RAR), and that the RA-RAR complex then binds to specific RA response
      elements in the DNA, modulating the expression of target genes. It is thus likely
      that RA improves at least some aspects of photoageing by modifying cellular
      differentiation programmes, as retinoids have been shown to do during
      embryogenesis, in malignantly transformed cells and in skin affected by certain
      dermatoses.

PMID- 1390182
TI  - Ozone depletion and its effects on human populations.
AB  - Concern about the ozone-depleting potential of man-made chemicals has led the
      United Nations to control their usage. Under the present arrangements, fully
      halogenated chlorofluorocarbons, halons and carbon tetrachloride will be phased
      out by the year 2000, and methylchloroform by the year 2005. Even so, atmospheric
      chlorine is expected to rise to seven times its natural level, so further ozone
      losses and greater ultraviolet B (UVB) exposure can be expected over heavily
      populated areas of the globe. Calculating changes in skin cancer incidence is a
      two-stage process which must take account of the increase in biologically
      effective UVB that results from an ozone loss of 1% (optical amplification
      factor, OAF) and the percentage increase in skin cancer incidence that results
      from a 1% increase in annual UV dose (biological amplification factor, BAF).
      Epidemiological data provide a BAF value of approximately 1.7 for basal cell
      carcinoma and 3.0 for squamous cell carcinoma. The absorption spectrum of ozone
      and the increased carcinogenic impact of UV radiation around 300 nm results in a
      value for OAF of approximately 1.6%; thus a 10% loss of ozone, if sufficiently
      sustained, would eventually increase the incidence of basal and squamous cell
      carcinomas by almost 30% and 50%, respectively. Dermatologists, therefore, need
      to look carefully at the environment in order to safeguard the health of future
      generations.

PMID- 1390183
TI  - Ageing and photoageing of the skin: observations at the cellular and molecular
      level.
AB  - It is now well established that ageing occurs at the level of individual cells in
      the skin and other organ systems. Changes in cell behaviour, protein production
      and gene expression in response to standardized stimuli are readily observed in
      cultured cells derived from young vs old donors and from photoaged vs sun
      protected body sites. Whether these changes are best viewed as a cause or a
      consequence of ageing cannot be determined at present. Nevertheless, available
      data now provide cellular and molecular correlates for the well-known differences
      in clinical responsiveness between newborn, adult and photoaged skin. From this
      basis, it will hopefully be possible to develop a more comprehensive
      understanding of cutaneous ageing processes.

PMID- 1390184
TI  - Long-term clinical experience with a topical retinoid.
AB  - Topical tretinoin is a well-established treatment for acne, with a low incidence
      of reported adverse effects, most of which are local skin reactions. The retinoid
      has limited absorption through the skin, so that even with repeated applications
      plasma concentrations do not exceed normal endogenous levels. In mice, lifetime
      treatment with topical tretinoin improved skin texture and did not have any
      tumorigenic effects. Data from multicentre clinical trials have shown that 0.05%
      tretinoin emollient cream reduced fine wrinkling, surface roughness and mottled
      hyperpigmentation caused by photodamage. Improvement of these clinical signs was
      maintained after 12 months of daily tretinoin therapy, and regressed slowly after
      cessation of therapy. However, maintenance of the visible effects of topical
      tretinoin was reported after continued therapy with once or three times weekly
      applications of tretinoin emollient cream. Data from multicentre studies
      suggested that 0.1% tretinoin cream has a potential role in the treatment of
      solar keratoses. It is concluded that the application of tretinoin to
      photodamaged skin used in conjunction with sunscreens and judicious sun exposure
      is an effective regimen to treat the damaging cutaneous effects of chronic sun
      exposure.

PMID- 1390185
TI  - The clinical identification and quantification of photodamage.
AB  - The distinction between intrinsic and extrinsic ageing can be made on both
      histological and clinical grounds. Clinical criteria associated with the
      diagnosis of extrinsic ageing are coarse wrinkles, actinic lentigines, elastotic
      conditions, purpura, telangiectasia and cutaneous neoplasms. These parameters are
      always superimposed on changes associated with intrinsic ageing: namely, fine
      wrinkles and benign growths. There is heightened interest in extrinsic ageing as
      a result of studies demonstrating the efficacy of topical tretinoin in improving
      this condition. As a consequence, systems for grading extrinsic ageing have been
      developed, including a photographic standard scale which removes some of the
      subjectivity inherent to current methodology.

PMID- 1390186
TI  - Pigmented lesions as a sign of photodamage.
AB  - Chronic exposure to ultraviolet (UV) radiation causes skin changes, known as
      photodamage. Apart from damage to the connective tissue of the dermis and to
      keratinocytes, pigmented lesions, known as 'age spots', occur. There are several
      types, but the most common lesions are the senile lentigines. The main
      differential diagnoses include reticular seborrhoeic keratosis and lentigo
      maligna, and histopathological examination is required for exact differentiation.
      Variants of lentigo senilis with acute onset after intense UV radiation are
      sunburn freckles. Psoralens- and UVA-induced freckles, and lentigines occur after
      phototherapy with artificial UV sources or use of sunbeds for cosmetic tanning.
      Ephelids are common genetically determined pigment spots appearing during
      childhood in a distinct photodistribution. Exposure to UV radiation also seems to
      play a role in the manifestation of acquired nevi. Since pigmented lesions in sun
      damaged skin represent more than one entity, they differ in their response to
      treatment. This should be taken into account when the efficacy of topical therapy
      is evaluated.

PMID- 1390187
TI  - Experience with tretinoin therapy in temperate regions.
AB  - In a previously reported study on the anti-photoageing effects of topical
      tretinoin, the following regimen produced good patient compliance: 0.01% for 1
      month, 0.025% for 1 month; and 0.05% for 4 months. The majority of patients
      (60/89) enrolled in the initial study continued to apply the cream to the face,
      and a further 140 patients were enrolled for a long-term study (mean duration 2
      years). The prolonged study showed that 91.4% of patients used tretinoin in an
      attempt to slow down skin aging, and 8.6% sought subjective skin benefits. Of the
      163 patients who completed the study, 58.8% sought an improvement of wrinkles,
      30.1% skin trophism and 14.7% reduced pigmentation. The product was used
      throughout the year by 66.9% of patients, but 8.0% stopped using it during the
      summer. A daytime moisturizing cream was required by 77.9% of patients, and 82.8%
      used a sunscreen in the summer. Tretinoin was applied to other areas of the body
      by 63.8% of patients.

PMID- 1390188
TI  - The measurement of photodamage.
AB  - The use of non-invasive and invasive techniques for the assessment of human
      photodamaged skin is reviewed. Physical changes during photodamage and its
      treatment are best scored using a visual analogue scale rather than a short, non
      equal interval scale. Epidermal thickness can be measured by histometric methods
      but dermal thickness can be measured non-invasively using pulsed A-scan and B
      scan ultrasound techniques. These approaches are not effective in detecting any
      changes due to photodamage. Mechanical properties of the dermis can be determined
      using either a static or a dynamic test mode. The authors have used extensometry
      to provide a measure of the laxity of skin. Replicas of the crow's foot areas
      have been taken before and after tretinoin treatment, and the replicas have been
      inspected by optical profilometry. Reductions of blood flow in photodamaged skin
      have been established using laser Doppler measurements, the effect being reversed
      by topical tretinoin. Invasive biochemical techniques have the disadvantage that
      they generally require large amounts of tissue. Cytochemical techniques, however,
      have shown increased glucose-6-phosphate dehydrogenase activity in the granular
      cell layer of patients with non-melanoma skin cancer, premalignant epidermal
      lesions, sun-damaged epidermis and artificially irradiated skin. This technique
      may provide an important model for the study of photodamage. It is concluded that
      there is no single method available to quantify the degenerative changes
      associated with photodamage and the effects of tretinoin.

PMID- 1390189
TI  - Endothelium and elastic tears in the afferent arteries of experimental
      arteriovenous fistulae in rabbits.
AB  - The endothelium and underlying internal elastic lamina of the arteries from 16
      carotid-jugular arteriovenous fistulae in rabbits were examined using the en face
      technique and scanning electron microscopy respectively. Tears appeared in the
      internal elastic lamina of the arteries 3 days post-operatively. The overlying
      endothelium exhibited cytoplasmic pallor, loss of argyrophilia of cell borders,
      and at times attenuated endothelial cells bridging thrombus covered regions of
      denudation. Early endothelial lesions repaired rapidly and were found only 3-7
      days post-operatively despite progressive increase in frequency and extent of
      tears and the development of interconnecting longitudinal tears with time.
      Following repair endothelial cells over the tears were small with hyperchromatic
      nuclei and oriented mostly parallel to the arterial axis. Endothelial cell
      density overlying these elastic tissue tears increase to three times that in
      contralateral arteriotomized common carotid arteries. These endothelial changes
      were sharply delineated by the margins of the elastic tears. Cell density over
      the tears reached its maximum 9-11 days post-operatively with mitotic figures
      both in the floor of the tears and over islands of residual elastic lamina. With
      time the cell density progressively diminished and endothelial cells assumed a
      more conventional elongated spindle shape.

PMID- 1390190
TI  - Histopathology of lymphoid organs in experimental leishmaniasis.
AB  - Hamsters (Mesocricetus auratus) were inoculated with L. (L.) chagasi and killed
      on days 7, 15, 30, 45 and 60 after infection. The lymphoid organs developed
      initial proliferation of the B lymphocyte zone with recovery by the 60th day
      group when pyroninophilic cells were prominent. The T lymphocyte area showed a
      progressive selective decrease of lymphocytes and cellular density with cellular
      pleomorphism including macrophages, plasma cells and reticular cells. The mean
      volume of the white pulp increased with the lymphoid follicle hyperplasia but
      returned to its initial level by day 60. The main red pulp change was marked
      hyperplasia of the phagocytic mononuclear cells containing parasites from the
      30th day of infection onward. These changes are compatible with the humoral and
      cellular immunoresponse found in patients with visceral leishmaniasis (VL).

PMID- 1390192
TI  - The effects of supra-therapeutic doses of rifampicin on liver function in the
      perfused rat liver.
AB  - The isolated liver perfusion model was used to study the effects of supra
      therapeutic doses of rifampicin on hepatic gluconeogenesis and bromosulphthalein
      (BSP) clearance from the perfusate and biliary excretion of the dye in the rat.
      Three groups of rats randomly assigned to a control and two experimental groups
      were studied; those in the experimental groups were given 4 mg rifampicin per os
      daily for 90 days. The control group was untreated. The livers of the control and
      one experimental group were perfused with a medium containing pyruvate and
      subsequently these livers were perfused with a medium containing
      bromosulphthalein. The livers of the second experimental group were subjected to
      histological examination. The rate and the concentration of glucose was
      decreased, lactate levels and lactate: pyruvate ratios were increased in the
      experimental animals. The mean perfusate BSP and biliary excretion of the dye was
      decreased in the experimental group. Fatty change was present in the livers of
      rifampicin treated rats. This study demonstrates that the isolated liver model
      has proved to be both suitable and useful for the study of the effects of drugs
      and that chronic administration of supra-therapeutic doses of rifampicin to rats
      adversely affected liver function. It also produces histological evidence of
      hepatic damage in rats.

PMID- 1390191
TI  - Ras gene mutation-independent tumours in the intestine of the rat by a single
      dose of N-methyl-N-nitrosourea.
AB  - Aiming at a sequential analysis of the role of ras gene point mutations during
      intestinal carcinogenesis, we established an experimental rat tumour model using
      N-methyl-N-nitrosourea (MNU) as an initiating agent as this carcinogen has been
      found to induce rat mammary carcinomas with a high prevalence of ras gene
      mutations. MNU treatment of a total of 249 rats (25 or 50 mg/kg i.p.) in various
      combinations with partial hepatectomy, hydroxyurea infusion and/or phenobarbital
      exposure resulted in a high incidence of intestinal adenomas and carcinomas of
      different histological types, besides liver, soft tissue and auditory sebaceous
      gland tumours. With PCR-amplified DNA the prevalence of mutations of codon 12 and
      61 of H-, K- and N-ras was determined in dot blots by hybridization with 32P
      labelled allele-specific oligonucleotides. Ras gene point mutations were not
      observed in any of the 41 intestinal rat tumours randomly selected from various
      experimental groups. Considering the high prevalence of ras mutations in MNU
      induced mammary carcinomas of the rat the observed complete lack of ras mutations
      in intestinal tumours induced in the rat by the same carcinogen suggests that
      organ-specific intraspecies differences in the mechanism of malignant
      transformation exist even for a heterolytically decomposing, direct acting
      carcinogen like MNU.

PMID- 1390194
TI  - Histologic evaluation of wound healing in experimental intestinal anastomoses:
      effects of antineoplastic agents.
AB  - Histologic evaluation of intestinal wound healing with and without cytostatics
      was performed in 36 rats. Variables were the relative position of the wound edges
      in mucosa and muscularis, necrosis, exudate, granulation tissue, granulocytes,
      macrophages, fibroblasts, restoration of the mucosal epithelium, and repair of
      the muscularis propria. The relative position of the wound edges in the mucosa
      and the muscularis in the initial phase of wound healing depended on technique
      but appeared to improve in the later phases of wound healing. It was not affected
      by the administration of antineoplastic agents; neither were muscularis repair,
      epithelial restoration of the mucosa, necrosis, nor exudate. Granulation tissue,
      fibroblasts and macrophages were present in maximal amounts after 7 days
      appearing later or showing this maximum at a different moment in time when
      antineoplastic agents were given. The processes of epithelial and muscularis
      repair were not influenced by the relative position of the wound edges.
      Granulation tissue, macrophages, and fibroblasts were the best parameters for
      measuring the histologic evolution of intestinal wound healing, and the effects
      of antineoplastic agents upon it.

PMID- 1390193
TI  - Structural and metabolic changes in articular cartilage induced by iodoacetate.
AB  - The chemically induced injury to articular cartilage, caused by two successive
      intra-articular injections of sodium iodoacetate, has been used in studies on the
      effects of anti-inflammatory and of potentially chondroprotective agents. It has
      been assumed that the injurious effects are caused by inhibition of the
      glycolytic pathway. In the present study this inhibition has been shown to be
      greater than expected from in vitro studies, and to influence equally other
      oxidative pathways. However, the response is clearly not a simple one in that
      some of the surface chondrocytes, and synovial lining cells in close proximity to
      the cartilage, show virtually no inhibition.

PMID- 1390195
TI  - Neutrophil-oxidized low density lipoprotein: generation in and clearance from the
      plasma.
AB  - The prevailing concept of an extremely rapid disappearance of 'modified' low
      density lipoprotein (LDL) from the circulation was reinvestigated. Rabbit LDL was
      'modified' by homologous activated (phagocytosing) polymorphonuclear leucocytes
      (PMLN), radiolabelled with a non-degradable ligand (125I-TC-LDL) and injected
      into rabbits. The plasma half-lives of 'modified' and native LDL were T1/2 = 2.5
      and 5.75 h, respectively. Furthermore, the possibility of LDL oxidation in plasma
      by stimulated PMNL was investigated. Hirudin-anticoagulated human plasma was
      incubated with unstimulated or stimulated autologous PMNL. Chemiluminometry
      (reactants with microperoxidase) of the lipid extract of plasma after incubation
      showed lipid peroxidation to be induced by phagocytosing, but not by quiescent,
      leucocytes. These findings show that in plasma, stimulated leucocytes can
      'modify' LDL and the circulatory half-life of the latter enables its contribution
      to atherogenesis.

PMID- 1390196
TI  - The seeding of human aortic endothelial cells on the extra-cellular matrix of
      human umbilical vein endothelial cells.
AB  - A post confluent layer (6th passage) of human umbilical vein endothelial cells
      (HUVECs) was treated with 3 mM ethylene diamine tetra-acetic acid (EDTA) to
      expose the subendothelial extra-cellular matrix (ECM). Normal human aortic
      endothelial cells (HAECs) harvested by mechanical scraping were seeded onto the
      ECM of the HUVECs. The cells quickly attached and proliferated with normal
      morphology. To ensure confluency the HAECs were pooled after a brief trypsin/EDTA
      incubation and seeded onto the ECM of the same HUVECs (6th passage) cell line.
      They attached within 2 hours, and the cells grew to confluence displaying
      cobblestone morphology characteristic of phenotypic endothelium. HUVECs (11th
      passage) were seeded onto (6th passage) HUVECs ECM. The cells attached,
      proliferated to confluence within the normal time interval (7-8 days) and were
      positively characterized. A Corvita 6mm graft supplied with a gelatin/heparin
      matrix was densely seeded with HUVECs (6th passage). These cells also
      proliferated to confluence. The implications for improving the design of arterial
      grafts are discussed.

PMID- 1390197
TI  - c-fms is present in primary tumours as well as in their metastases in bone
      marrow.
AB  - The expression of c-fms oncoprotein in different primary tumours as well as in
      their metastases in bone marrow, was shown. All the samples were fixed and
      processed by the acetone, methyl benzoate, xylene procedure (AMeX), which was
      suitable for studying oncoprotein expression not only in primary tumours but also
      in bone marrow (BM) biopsies. Among the patients suffering from acute myeloid
      leukaemia (AMeL), positive c-fms cells were found in 55% cases. On the contrary,
      patients with lymphocytic cell disorders have not had detectable c-fms oncogene
      product in BM biopsies.c-fms oncoprotein was also detected in some primary tumour
      specimens (lung carcinoma, cervical carcinoma, gastric carcinoma, breast
      carcinoma and melanoma) and their metastases in BM, while it was not present in
      normal uterine tissue. There was a positive correlation between c-fms oncoprotein
      expression in primary and metastatic tumours. Our results showed that c-fms
      product is confined, not only to some normal, but also to the variety of
      malignant cells of different origin.

PMID- 1390199
TI  - Brachial artery embolus.

PMID- 1390200
TI  - Acute lower limb ischemia: a case study.
AB  - Acute ischemia of the lower extremity is a limb and life-threatening situation
      that demands prompt recognition and immediate treatment. The leading cause of
      acute limb ischemia is typically an arterial embolus of cardiac origin. Other
      significant causes are thrombosis of an atherosclerotic vessel and arterial
      injury/trauma. This case study examines complexities of diagnosis and treatment
      of acute ischemia while focusing on nursing care of a patient with an acute
      embolic occlusion.

PMID- 1390198
TI  - Current status review: cerebral amyloid.

PMID- 1390201
TI  - Vascular nursing research review: 1980--1990.
AB  - The specialty of vascular nursing has developed and flourished over the last
      decade. Recently, the vascular nursing literature has grown tremendously. Nurse
      researchers have begun to explore the unique needs of individuals with vascular
      disease. Areas currently under investigation include individual and family
      adaptation to vascular disease and clinical therapeutics for individuals with
      vascular disease. The research literature from 1980 to 1990 is examined to
      determine the amount and major themes of vascular nursing research. Unexplored
      areas of vascular nursing are identified, and recommendations for future research
      proposed.

PMID- 1390202
TI  - Thrombolytic therapy for treatment of acute peripheral arterial occlusion.
AB  - Thrombolytic therapy is becoming a more widely utilized treatment modality for
      treatment of acute peripheral arterial occlusions. Nurses, therefore, need to be
      knowledgeable of the patient care management issues that surround thrombolytic
      therapy. This article, through a case study approach, defines the mechanism of
      action of thrombolytic agents, side effects, and key patient management issues.
      Nursing interventions focus on potential for fluid volume deficit related to
      alteration in hemostasis mechanisms/clot dissolution and potential alteration in
      tissue perfusion, peripheral/cerebral, related to thrombosis/embolus/clot
      dissolution.

PMID- 1390203
TI  - Referrals: where will they come from?

PMID- 1390204
TI  - Limb loss in the elderly peripheral vascular disease patient.
AB  - Limb loss in the elderly is a significant problem for a number of reasons. One of
      the primary problems this patient population experiences is rehabilitation.
      Regaining independence following amputation is often a slow and painful process.
      In addition, studies reveal a high incidence of depression as well as increased
      mortality rates in the elderly population following amputation. Nurses can play a
      key role in assisting the patient in attaining the highest level of function
      possible following limb loss. Nursing interventions should focus on coordinating
      a team approach to care of the amputee, educating both patient and family, as
      well as encouraging patient participation in support groups.

PMID- 1390205
TI  - Acute promyelocytic leukaemia.

PMID- 1390206
TI  - The function of gamma delta T cells.

PMID- 1390207
TI  - Clonal lymphocytes are detectable in only some cases of MDS.
AB  - Clonal analysis of lymphocytes from patients with myelodysplastic syndrome (MDS)
      has been carried out using X-chromosome inactivation patterns detected by the
      probe M27 beta, and by polymerase chain reaction amplification of the
      immunoglobulin heavy chain gene hypervariable region, CDR3. Of 32 female patients
      heterozygous for M27 beta only seven (22%) demonstrate monoclonality of
      peripheral blood lymphocytes. 12 (37%) give unequivocal polyclonal results and
      the remaining cases give patterns of X-inactivation which cannot be interpreted
      either way. A study of 68 MDS patients showed five (7%) with a population of B
      cells with a monoclonal rearrangement of CDR3 compared with none out of 60 normal
      individuals, none out of 15 with B-non Hodgkin lymphoma (B-NHL) in remission and
      19 out of 25 (75%) of cases of B-chronic lymphocytic leukaemia (B-CLL).
      Monoclonal lymphocytes were found by both techniques in only two females with
      MDS. We conclude that the presence of polyclonal lymphocytes is a common finding
      in patients with MDS.

PMID- 1390209
TI  - Detection of allele-specific expression of N-RAS oncogenes in human leukaemia
      cells.
AB  - We report analysis of allele-specific expression of N-RAS transcripts in myeloid
      leukaemic cells and cell lines. Expression was assessed by an assay of reverse
      transcription/PCR combined with differential hybridization with mutation-specific
      oligonucleotides. In cells from all patients with acute myeloid leukaemia (AML)
      and in myeloid cell lines HL-60 and THP-1, expression of both the wild-type
      allele and the abnormal allele altered by a point mutation could be detected,
      albeit not always at comparable levels. This might be due for instance to allelic
      exclusion. The assay described provides a means of analysing the degree of
      expression of dominant oncogenes.

PMID- 1390208
TI  - Detection of latent subclones with abnormal karyotypes by long-term bone marrow
      cultures in cases of myelodysplastic syndrome.
AB  - Cytogenetic studies on non-adherent cells from long-term bone marrow cultures
      (LTBMC) were done for 23 patients with myelodysplastic syndrome (MDS) and
      compared with the karyotypes detected during their clinical courses. Of 14 cases
      with normal karyotype before culture, abnormal karyotypes were detected first in
      LTBMC from seven. Novel abnormal karyotypes were observed after LTBMC in two of
      four cases which had had both normal and abnormal karyotypes before culture.
      Abnormal karyotypes were also newly detected in four of five cases with only
      abnormal karyotypes before culture. Among 13 cases in which abnormal karyotypes
      were observed during the cultures, three patients showed the same karyotypes 1-11
      months later in their clinical courses. These findings suggest that our LTBMC
      might be useful for evaluating the prognosis and choice of treatment for MDS
      patients.

PMID- 1390210
TI  - Relapse into blast crisis following bone marrow transplantation for chronic phase
      chronic myeloid leukaemia: a report of five cases.
AB  - A proportion of patients receiving allogeneic bone marrow transplants (BMT) for
      chronic myeloid leukaemia (CML) in first chronic phase relapse; most of these
      relapses show features of chronic phase disease. We report here a series of five
      patients seen at a single institution over a 10 year period who developed blast
      crisis as the first sign of relapse after BMT for CML in chronic phase. The blast
      cells were myeloid in three cases and lymphoid in two. In one case the relapse
      may have occurred in cells of donor origin. The possible explanations for this
      unusual sequence of events include incipient transformation that was not detected
      before BMT, undetected relapse into chronic phase proceeding into transformation
      post-BMT, and transformation occurring de novo post-BMT in small numbers of
      residual leukaemic stem cells.

PMID- 1390211
TI  - HLA-identical sibling donor bone marrow transplantation for chronic myeloid
      leukaemia in first chronic phase: influence of GVHD prophylaxis on outcome.
AB  - We have analysed the results of treating 140 consecutive patients with chronic
      myeloid leukaemia (CML) in chronic phase by bone marrow transplantation (BMT)
      using marrow from HLA-identical siblings performed between February 1981 and July
      1991. Three different regimens were used sequentially to prevent graft-versus
      host disease (GVHD): cyclosporin A (CsA) alone (n = 39), T-cell depletion of
      donor marrow (n = 51) and CsA with methotrexate (MTX) (n = 50). Eighty-four
      patients (61%) survive at a median of 49 months from BMT (range 3-120). The
      actuarial overall and leukaemia-free survivals at 5 years were 52% and 41%
      respectively. The actuarial probabilities of leukaemia-free survival and
      haematological relapse at 2 years for the CsA only group were 65% and 4%, for the
      T-cell depletion group 40% and 41% and for the CsA/MTX group 68% and 6%
      respectively. For the T-cell depletion group the probability of leukaemia-free
      survival was significantly lower (P less than 0.001) and the probability of
      relapse significantly higher (P less than 0.001) than for other methods of GVHD
      prophylaxis; differences between the other two groups were not significant.
      Previous reports that T-cell depletion with Campath-1M results in a high rate of
      relapse are confirmed. Patients in the CsA/MTX group have been monitored with
      cytogenetic and polymerase chain reaction studies for residual BCR/ABL
      transcripts. We conclude that the combination of CsA/MTX is currently the best
      available approach to prevention of GVHD after BMT for CML and in our hands it is
      not associated with a major risk of relapse.

PMID- 1390212
TI  - Malignant transformation and life expectancy in monoclonal gammopathy of
      undetermined significance.
AB  - The actuarial probability of malignant transformation and the impact on expected
      survival were analysed in a series of 128 persons diagnosed with monoclonal
      gammopathy of undetermined significance (MGUS) over a 20-year period. At a median
      follow-up of 56 months the M-component remains stable in 101 patients (78.9%), 14
      patients (10.9%) have died from non-related disorders and 13 (10.2%) have
      developed malignant transformation of MGUS (multiple myeloma, 10; primary
      amyloidosis, two; Waldenstrom's macroglobulinaemia, one). The actuarial
      probability of malignant transformation at 5 and 10 years was 8.5% and 19.2%,
      respectively. When different presenting features were analysed for predictive
      value of the malignant transformation, the IgA type of MGUS was the only variable
      associated with a higher probability of such an event (P less than 0.025).
      Although no significant difference was observed between the survival probability
      of persons with MGUS and that of the control population, the development of
      malignant transformation was associated with a shorter survival (P less than
      0.001).

PMID- 1390213
TI  - Platelet alloimmunization after multiple transfusions: a prospective study of 50
      patients.
AB  - Fifty polytransfused patients were prospectively studied to determine the
      frequency of post-transfusion alloimmunization and its influence on the response
      to platelet transfusion. Platelet- and HLA-specific antibodies were detected by
      means of the standard and antiglobulin-augmented lymphocytotoxicity techniques
      (LCT), the platelet suspension indirect immunofluorescence test (PSIIFT), and
      monoclonal antibody immobilization of platelet antigens (MAIPA). HLA antibodies
      were detected in 13 patients (26%) (IgM = 6; IgG = 6; IgM + IgG = 1). The
      standard LCT was positive in 12 of these 13 patients. Complement-independent HLA
      antibodies, only detectable in the PSIIFT and the antiglobulin-augmented LCT,
      were documented in two patients and were associated with poor post-transfusion
      platelet recovery in the patient who could be evaluated. All the HLA antibodies
      were detected in the PSIIFT, while only four were detected in the MAIPA. Platelet
      specific alloantibodies were found in two patients by means of PSIIFT or MAIPA
      and may have led to poor post-transfusion platelet recovery in one patient.
      Platelet autoantibodies were detected in two patients but were not associated
      with platelet refractoriness. Paraformaldehyde-dependent platelet antibodies were
      detected in 11 patients but were not associated with platelet refractoriness.

PMID- 1390214
TI  - Unique expression of von Willebrand factor by type IIA von Willebrand's disease
      endothelial cells.
AB  - Endothelial cells (EC) were cultured from the umbilical cord of a male neonate
      whose mother was previously diagnosed with type IIA von Willebrand's disease
      (vWd). The diagnosis of type IIA vWd in the proband was confirmed by low
      ristocetin activity and the absence of the highest molecular weight (MW) forms of
      von Willebrand factor (vWf) in his platelet poor plasma. The vWf of EC cultured
      from the neonate's umbilical cord differed from that of control EC and the cell
      line EA.hy926 in two respects. Firstly, the full range of molecular weight forms
      was present in the patient EC lysate and, secondly, vWf:Ag expression was
      approximately seven-fold greater than that of control cells. Platelet lysates
      prepared from other affected members of the type IIA vWd family in the presence
      or absence of proteolytic inhibitors demonstrated a near normal vWf multimeric
      distribution. Resistance of these high MW forms to heat degradation was conferred
      by the presence of proteolytic inhibitors. Moreover, the full plasma vWf
      multimeric distribution could not be restored by the inclusion of EDTA. N
      ethylmaleimide and leupeptin in the anticoagulant during the rapid preparation of
      platelet poor plasma. These findings lend support to the heterogeneous nature of
      type IIA vWd and has possible implications in the understanding of the
      intracellular processes involved in the biosynthesis and storage of the vWf
      macromolecular complex as well as the pathogenesis of type IIA vWd.

PMID- 1390215
TI  - Human parvovirus B19 in clotting factor concentrates: B19 DNA detection by the
      nested polymerase chain reaction.
AB  - The presence of B19 parvovirus in plasma from blood donors is seldom
      demonstrable, but clotting factor concentrates, prepared from large plasma pools,
      may be able to transmit B19 virus infection, and the effectiveness of different
      chemical and physical treatment to inactivate this virus is not yet known. In
      this study we report on the detection of B19 DNA in 25 clotting factor
      concentrates, prepared by a variety of procedures of purification and
      inactivation; dot blot hybridization and Southern blot hybridization assays, as
      well as a 'nested' polymerase chain reaction (PCR) have been employed. Nine out
      of 25 products were B19 DNA positive by PCR, whereas only two gave positive
      results by hybridization techniques. B19 DNA positive concentrates have been
      found in 'untreated' products but also in some solvent/detergent or steam-treated
      products and even in monoclonal purified concentrates. PCR may be useful for the
      screening of blood products to be used in immunocompromised haemophiliacs,
      particularly in HIV positive subjects, at risk of severe chronic anaemia
      following B19 infection.

PMID- 1390216
TI  - Plasmodium falciparum: diversity of isolates from Malawi in their cytoadherence
      to melanoma cells and monocytes in vitro.
AB  - We observed considerable diversity in the cytoadherence of Plasmodium falciparum
      isolates from Malawi to melanoma cells, U937 cells and human peripheral
      monocytes. Each isolate exhibited a unique cytoadherence profile for the three
      human cell types. These isolates generally adhered well to U937 cells and fresh
      monocytes, moderately to melanoma cells and poorly to TE 671, MIA-Pa-Ca, WI 38,
      PLC/PRF/5 and HeLa cells. An antimalarial immunoglobulin pool inhibited binding
      to melanoma cells by 50% or more and to U937 cells by 25% or less. There was no
      correlation between in vitro cytoadherence to the three cells and clinical
      disease. These results suggest that malarial adherence ligands exposed on the
      surface of infected erythrocytes vary from one isolate to another.

PMID- 1390217
TI  - Substituted benzaldehydes (12C79 and 589C80) that stabilize oxyhaemoglobin also
      protect sickle cells against calcium-mediated dehydration.
AB  - Reversibly sickled cells from patients with homozygous sickle-cell disease were
      prepared by Percoll-Isopaque density gradient separation and subjected to 15 h of
      cyclical deoxygenation-reoxygenation in the presence of Ca. After 15 h the sickle
      cells became dehydrated, losing volume secondary to K efflux via the Ca-activated
      (Gardos) channel, and showed impaired filterability through 5 microns diameter
      pores. The substituted benzaldehydes 12C79 and 589C80, which stabilize the oxy
      conformation of sickle haemoglobin, showed an additional protective effect at
      pharmacological concentration by maintaining the K concentration, mean cell
      volume, and deformability of sickle cells. Drugs that increase the oxygen
      affinity of sickle haemoglobin may be more effective than specific inhibitors of
      Ca entry or K efflux in preserving the cation homeostasis and deformability of
      sickle cells during sickling in vivo.

PMID- 1390218
TI  - Rare occurrence of P53 gene mutations in multiple myeloma.
AB  - We looked for mutations of exons 5-8 of the P53 gene in bone marrow cell from 37
      cases of multiple myeloma, using polymerase chain reaction-single strand
      conformation polymorphism (PCR-SSCP) analysis and DNA sequencing. 25 patients
      also had cytogenetic analysis. A point mutation, leading to an amino acid change
      in the P53 protein was found in only one case, involving exon 5. These findings
      suggest that P53 mutations are very rare in multiple myeloma, and that this
      disease may be categorized among the few neoplasms where P53 abnormalities have
      very limited role, if any.

PMID- 1390219
TI  - All-trans retinoic acid improves erythropoiesis in myelodysplastic syndromes: a
      case report.

PMID- 1390220
TI  - Deep venous thrombosis and pulmonary embolism in a patient with type III von
      Willebrand's disease, protein C and antithrombin III deficiency.

PMID- 1390221
TI  - Transient neurologic disturbances in a child treated with moderate-dose
      methotrexate.

PMID- 1390222
TI  - Can myelodysplasia evolve into aplastic anaemia?

PMID- 1390223
TI  - Effect of IFN alpha therapy on secondary Ph1-positive clones.

PMID- 1390224
TI  - Red cell macrocytosis and chronic obstructive airways disease.

PMID- 1390225
TI  - Predicting response to splenectomy in thrombocytopenic children.

PMID- 1390226
TI  - Effective treatment of relapsed acute myeloid leukaemia with drugs chosen by DiSC
      assay.

PMID- 1390227
TI  - Mutation of p53 gene does not play a critical role in myelodysplastic syndrome
      and its transformation to acute leukaemia.

PMID- 1390228
TI  - Clinico-pathological features of minimally differentiated acute myeloid leukaemia
      (AML-MO)

PMID- 1390229
TI  - Ticlopidine and severe aplastic anaemia.

PMID- 1390230
TI  - Responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to
      recombinant human erythropoietin (rh-Ep) in vitro in multiple myeloma.
AB  - The responsiveness of bone marrow erythroid progenitors (CFU-E and BFU-E) to
      recombinant human erythropoietin (rh-Ep) was investigated in vitro in 21 patients
      with multiple myeloma to assess the clinical usefulness of rh-Ep in this disease.
      CFU-E and BFU-E assays were performed by methylcellulose culture methods. The
      myeloma patients were divided into two groups according to the percentage of
      plasma cells in the bone marrow (over 50% and under 50%). Among the patients with
      few plasma cells, some revealed normal CFU-E and BFU-E growth at 2 units of rh
      Ep, and no further increase was observed even with an increasing dose of rh-Ep.
      Among the other patients, more than half demonstrated a good response to rh-Ep.
      Among the patients with a high percentage of plasma cells, some revealed no
      response to rh-Ep, but there were patients with a high percentage of plasma cells
      in the bone marrow who had a good response to rh-Ep. High doses of rh-Ep may be
      clinically effective in some patients with multiple myeloma independently of the
      level of plasma cells in the bone marrow.

PMID- 1390231
TI  - Purification of human monocyte-specific esterase (MSE): molecular and kinetic
      characteristics.
AB  - Human monocyte-specific esterase (MSE) derived from leukaemic AMoL-M5 blast cells
      was purified to homogeneity by the sequential application of anion-exchange,
      hydrophobic interaction, affinity and gel filtration chromatographic procedures.
      The resulting enzymatically active MSE primarily existed as an apparent trimer
      which, under both reducing and non-reducing conditions, dissociated to an
      inactive 63.4 kD glycoprotein monomer. Electrophoretic studies further confirmed
      that purified MSE comprised a narrow series of pI (5.5-6.1) forms and one main
      charge species. Neuraminidase failed to modify observed pI values for individual
      MSE isoenzymes, and endoglycosidase H treatment revealed that the deglycosylated
      form of MSE had an apparent molecular weight of 60.1 kD. In support of the known
      cytochemical characteristics of human MSE, substrate kinetic studies demonstrated
      that purified enzyme hydrolysed esters of higher acyl chain length (butyrate >
      propionate > acetate) but did not show peptidase activity. Amino acid sequencing
      of the MSE N-terminus further revealed that there was almost complete identity
      with human alveolar macrophage esterase and close similarities with rat and
      rabbit liver carboxylesterases. These kinetic and molecular studies are
      particularly important in elucidating the biological and functional role(s) of
      one of the few haemopoietic cell enzymes that can be considered truly lineage
      specific.

PMID- 1390232
TI  - Modulation of tissue factor on human monocytes by cisplatin and adriamycin.
AB  - Coagulation disorders have been associated with the use of chemotherapeutic
      drugs. Pharmacological doses of cisplatin and adriamycin directly induced low
      levels of procoagulant on normal human blood monocytes and on a human
      myelomonocytic cell line, RC2a. Activity was maximal after 24 h and was not due
      to cell lysis as increasing drug doses which decreased cell viability were less
      effective. Procoagulant induction was markedly enhanced in the presence of
      bacterial lipopolysaccharide (LPS), with as little as 10-100 pg/ml LPS
      potentiating the cisplatin response by 2-5-fold and more than doubling the
      adriamycin response. Greater than 90% of the procoagulant activity was membrane
      bound tissue factor as indicated by the factor VII-dependent generation of factor
      Xa by viable cells and by the neutralization of this activity by a monoclonal
      antibody to tissue factor. Tissue factor antigen was measured simultaneously by
      immunohistochemical staining and by cell ELISA. Blood monocytes activated with
      LPS expressed high levels of tissue factor antigen; by contrast, adriamycin and
      cisplatin did not appear to induce antigen expression, but to enhance the
      specific activity of that already present. Results suggest that membrane
      alterations which occur following treatment with DNA/RNA intercalating drugs, may
      result in a highly active form of monocyte/macrophage tissue factor which may
      contribute to the complications caused by activated coagulation. Secondary Gram
      negative infection or cytokines released by an active immune response to a tumour
      may contribute to the procoagulant potential of these cytotoxic drugs.

PMID- 1390233
TI  - P53 gene mutations in acute myelogenous leukaemia.
AB  - A polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)
      assay was used to identify the exons which contained point mutations in the
      conserved regions (exons 4-8) of the p53 gene in 49 acute myelogenous leukaemia
      (AML) patients. SSCP analysis in our study was consistent with the results of
      subsequent direct DNA sequencing in detecting point mutational change in exons 5
      and 8 of one AML patient and in exons 7 and 8 of two additional AML patients. The
      mutations were located at codons 245 and 273, which have been found in many other
      tumours, and codons 178 and 290, which have not been reported previously. All of
      the p53 proteins in which we detected point mutations were immunoprecipitated by
      the p53 monoclonal antibody PAb 240, which has been shown to recognize a mutant
      conformation of p53 protein. Thus, our results indicate that functional
      inactivation of the p53 gene by point mutational change might be one of the
      mechanisms underlying disease progression of AML.

PMID- 1390234
TI  - Myelodysplastic syndromes in childhood: a population based study of nine cases.
AB  - Nine cases of de novo myelodysplastic syndromes (MDS) in childhood from a
      population based study are presented. The annual incidence of MDS was
      3.4/1,000,000 in children less than 15 years old, corresponding to 8.7% of all
      haematological malignancies in childhood. Two patients had Down's syndrome. None
      of the remaining patients had constitutional anomalies. All patients were
      classified according to the FAB classification. Five patients presented with
      refractory anaemia (RA), only one of these did not progress, one showed clonal
      evolution, and the remaining three patients all progressed to refractory anaemia
      with excess of blasts (RAEB). Three patients presented with RAEB. Two progressed
      to overt leukaemia. The last patient was classified as chronic myelomonocytic
      leukaemia (CMML). Clonal cytogenetic abnormalities were detected in five
      patients, in three of them as monosomy 7. Five patients have died; two of
      progressive disease, two of infections, and one of haemorrhage, two of the latter
      three patients died during therapy induced cytopenia. Of the four patients still
      alive, one patient showed a complete remission after cyclosporine and later
      immunoglobulin therapy, one patient is a long-term survivor after allogeneic bone
      marrow transplantation, and one patient apparently obtained a spontaneous
      remission several months after chemotherapy.

PMID- 1390235
TI  - Extended cytogenetic follow-up of patients with myelodysplastic syndrome (MDS).
AB  - The prognostic significance of clonal karyotype status in myelodysplastic
      syndrome (MDS) is assessed after an extended follow-up period of 5 years. There
      are three karyotype, single abnormalities or multiple abnormalities at the time
      of referral. However, there is no correlation between the size of the abnormal
      clone and prognosis. Karyotype status has independent prognostic significance in
      'high risk' MDS so that patients with a refractory anaemia with excess of blasts
      (RAEB)/RAEB in transformation (RAEB-t) and a normal karyotype survive
      significantly longer than those with an abnormal karyotype (P < 0.001) and do not
      differ significantly from patients with refractory anaemia (RA). Significant
      differences in survival according to karyotype status are also seen in patients
      with chronic myelomonocytic leukaemia (P < 0.001) but not in those with primary
      acquired sideroblastic anaemia and RA. Among patients studied sequentially, those
      who retained a normal karyotype survived significantly longer than those who
      developed an abnormality on follow-up (P < 0.001). The risk of leukaemic
      transformation was also increased in patients who presented with or subsequently
      developed a clonal karyotype abnormality compared with those who remained normal
      (P < 0.05).

PMID- 1390236
TI  - A predictive model for the clinical response to low dose ara-C: a study of 102
      patients with myelodysplastic syndromes or acute leukaemia.
AB  - The response to treatment with low-dose ara-C was studied in 102 consecutive
      patients; 79 with myelodysplastic syndrome (MDS) and 23 with acute myelogenous
      leukaemia (AML) following MDS. The aim was to find variables that could predict
      the response to treatment. All patients had clinical symptoms related to
      cytopenia. Peripheral blood values, bone marrow morphology histology and
      chromosomes were analysed before the start of treatment. The median survival of
      the patients was 9 months and a poor survival was predicted by advanced age, low
      platelet counts, the presence of pseudo-Pelger morphology and > or = 2
      chromosomal aberrations. Thirty patients (29%) responded with either a complete
      remission or a significant increase in haemoglobin level. For the remaining 71%,
      the treatment was ineffective and in some cases hazardous. The factors associated
      with a poor response to treatment could be divided into two groups: one included
      low platelet counts and the presence of chromosomal aberrations, both signs of
      progressive MDS with a short survival, and the other comprised morphological
      findings, indicating ineffective haemopoiesis. Patients with platelet counts >
      150 x 10(9)/l had a response rate of 55% compared to 23.5% in patients with
      subnormal platelet counts. Logistic regression identified low bone marrow
      cellularity, absence of ring sideroblasts and < 2 chromosomal aberrations as
      predictors of a favourable response in patients with platelet counts < 150 x
      10(9)/l. These factors and the platelet count were combined in a predictive model
      which can divide patients into three groups with different probabilities of
      response: a favourable group, 38.6% of the patients, with a response rate of >
      50%, an intermediate group, 32.7% of the patients, with a response rate of 24%,
      and an unfavourable group, 28.7% of the patients, with only 3% responses. While
      low-dose ara-C is an effective treatment for some patients, it is ineffective and
      hazardous for others. We present a model that can facilitate therapeutic decision
      making in two-thirds of patients with MDS and MDS-AML by identifying patients who
      should not be treated with low-dose ara-C as well as patients with a relatively
      high probability of response.

PMID- 1390238
TI  - Combination therapy with interferon alpha-2b plus low-dose interferon gamma in
      pretreated patients with Ph-positive chronic myelogenous leukaemia.
AB  - Between March 1988 and July 1990, 28 adults with chronic myelogenous leukaemia
      (CML) were treated with a combination of recombinant human interferon (IFN) alpha
      2b s.c. (initial dose 4 x 10(6) U/m2) and recombinant human IFN gamma s.c. (50
      micrograms totally) daily. All patients were in chronic phase disease and had
      been treated previously with chemotherapy or bone marrow transplantation. A
      complete haematologic remission was achieved in three patients (11%), a
      haematologic remission in 12 patients (43%), and a partial haematologic remission
      in seven patients (25%). Six patients did not respond to this schedule. Acute
      side-effects were flu-like symptoms, fever and chills. During long-term treatment
      six patients developed polyarthralgia. Haematotoxicity WHO grade III occurred in
      three patients, and WHO grade IV in two patients. One patient developed
      psychosis, and in another patient an exacerbation of a pre-existing sarcoidosis
      was observed. We conclude that this combination is tolerable and effective in
      inducing haematological remissions in pretreated CML patients.

PMID- 1390237
TI  - Two myelodysplastic syndrome cases with the inv(11)(p15q23) as a sole chromosomal
      abnormality.
AB  - Two myelodysplastic syndrome cases (one with acute nonlymphocytic leukaemia (M2)
      transformed from myelodysplastic syndrome (MDS), and the other with chronic
      myelomonocytic leukaemia following refractory anaemia with excess of blasts in
      transformation) showed the inv(11)(p15q23) as a sole chromosomal abnormality.
      Gene probes for c-Ha-ras-1 and c-ets-1 were hybridized to metaphase cells from
      bone marrow of these patients. c-ets-1 gene, which is mapped to 11q23, was
      demonstrated to have translocated to the short arm in the rearranged chromosome
      11 in both cases. On the other hand, c-Ha-ras-1 gene, which is located at 11p15,
      was translocated to the long arm in the rearranged chromosome 11 in patient 1,
      and deleted in patient 2. Our findings suggest that there may be heterogeneity in
      molecular events involved in the chromosomal rearrangement among the inv(11)
      carrying MDS.

PMID- 1390239
TI  - Mixed phenotype of blasts in acute megakaryocytic leukaemia and transient
      abnormal myelopoiesis in Down's syndrome.
AB  - Blasts from eight cases with acute megakaryoblastic leukaemia (AMKL) and seven
      with transient abnormal myelopoiesis in Down's syndrome (TAM) were investigated
      to clarify their phenotypic characteristics. CD41 and CD7 were the most
      frequently expressed in both disorders. CD41 was positive in six TAM and five
      AMKL cases, and CD7 was positive in five TAM and five AMKL cases, respectively.
      CD33 was detected in four TAM and five AMKL cases. Other myeloid-lineage
      associated antigens such as CD13 and CD11b could not be found in TAM but were
      expressed in five AMKL cases. Interestingly, CD56, a neural adhesion molecule,
      was expressed in three of four TAM and one of five AMKL cases. Cytoplasmic CD3
      antigen was also noted in three of five examined cases. A short-term culture
      study was conducted on blasts from two TAM cases and five AMKL cases. In two
      cases in which CD41 was not expressed before culture, the expression of CD41 was
      enhanced after culture with or without 12-O-tetradecanoyl-phorbol-13-acetate
      (TPA). The expression of CD7 remarkably was depressed, while that of CD13 was
      enhanced after culture with TPA. These findings suggest that blasts of TAM and
      AMKL originate from very immature cells and represent a mixed phenotype. In the
      present study, distinction of phenotypical differences between blast in TAM and
      AMKL was not possible.

PMID- 1390240
TI  - Shedding of CD9 antigen by bone marrow cells from patients with acute
      lymphoblastic leukaemia.
AB  - The levels of soluble CD9 antigen released into spent medium from bone marrow
      (BM) cells were assayed using a unique enzyme-linked immunosorbent assay. We
      demonstrated that a considerable amount of soluble CD9 antigen was consistently
      detected in the spent medium from CD9+ leukaemic blasts, but little from normal
      or regenerating BM cells. The sensitivity and specificity of CD9 antigen assay
      were tested. First, BM cells taken from patients in complete morphologic
      remission (CR) were studied, and the distinct level of CD9 antigen was detected
      in 16.3% of the cases. Second, the outcome of leukaemic patients with significant
      shedding of CD9 antigen from BM cells while in CR was investigated: all patients
      have developed systemic relapse within 5-24 (median 15.4) weeks. In contrast,
      24/34 patients without the increase of CD9 antigen levels are still in CR (follow
      up 19-149 weeks, median 56.2 weeks). Only 10 patients in this group have relapsed
      so far. No false-positive results were detected with this sensitive assay for
      soluble CD9 antigen, and the introduction of appropriately planned prospective
      studies is justified on the basis of these observations.

PMID- 1390241
TI  - A monoclonal antibody (NMC-VIII/10) to factor VIII light chain recognizing
      Glu1675-Glu1684 inhibits factor VIII binding to endogenous von Willebrand factor
      in human umbilical vein endothelial cells.
AB  - The monoclonal antibody NMC-VIII/10 is a neutralizing antibody which recognizes
      the Glu1675-Glu1684 sequence of the factor VIII light chain and inhibits factor
      VIII (FVIII) binding to immobilized von Willebrand factor (vWf). In this study we
      immunohistochemically determined, using human umbilical cord tissue, whether or
      not NMC-VIII/10 has an inhibitory effect on FVIII binding to endogenous vWF in
      endothelial cells. Tissue sections were reacted with purified FVIII followed by
      peroxidase-conjugated monoclonal antibody (C5) recognizing the 54 kD fragment of
      the FVIII heavy chain. The labelling pattern of bound FVIII was similar to that
      of endogenous vWF and appeared as a fine granular deposit in the endothelial
      cells. Addition of purified vWF completely inhibited the binding of FVIII to
      endothelial cells. Furthermore, FVIII did not bind to endothelium in the presence
      of 0.25 M CaCl2, and similarly, thrombin-treated FVIII did not bind to the
      vascular site. These findings suggested that FVIII was bound to endogenous vWF in
      the endothelial cells. The binding reaction was completely inhibited by NMC
      VIII/10, confirming that the monoclonal antibody recognizes the specific epitope
      responsible for FVIII binding to endogenous vWF.

PMID- 1390243
TI  - HLA-DR expression by platelets in acute idiopathic thrombocytopenic purpura.
AB  - Induction of expression of MHC class II antigens on the surface of cells that do
      not ordinarily express these proteins has been implicated in the pathogenesis of
      autoimmunity in diabetes mellitus and autoimmune thyroiditis. Platelets express
      class I but not class II HLA antigens. In this report, we describe a child with
      acute idiopathic thrombocytopenic purpura who at the time of the thrombocytopenic
      episode had class II (HLA-DR) antigens on his platelets. Following recovery, the
      HLA-DR antigens were no longer present on the platelets. We postulated that class
      II had been induced on his megakaryocytes by a cytokine such as interferon gamma,
      and that the induced expression of class II antigens contributed to the
      autoimmune disorder. To substantiate this possibility we next studied class I and
      II antigen expression on an erythroleukaemia cell line (HEL), which has many
      megakaryocytic features. Following treatment of HEL cells with interferon gamma,
      class I expression was increased and HLA-DR antigens were induced. These
      observations suggest that cytokine-mediated induced HLA-DR expression may
      contribute to the pathogenesis of a subset of thrombocytopenias.

PMID- 1390242
TI  - Plasma factor VII and thrombin-antithrombin III levels indicate increased tissue
      factor activity in sickle cell patients.
AB  - Although the mechanisms involved in the persistent clinical complications of
      sickle cell disease have not yet been fully delineated, previous studies suggest
      that sickle cell (HbSS) patients have a disposition to generate more thrombin and
      plasma in vivo than normal subjects. The reasons for the impaired regulation of
      haemostasis in HbSS patients is poorly understood. We report studies evaluating
      the extent to which in vivo coagulation and fibrinolysis are altered in HbSS
      patients in steady state. The concentrations of total factor VII (F(VII)t),
      factor VII zymogen (F(VII)z), thrombin-antithrombin III (TAT), fibrinopeptide
      A(FPA), and fibrin D-dimer in plasmas of 50 normal controls (HbAA) and 45 HbSS
      steady state patients, were measured using sensitive and specific enzyme-linked
      immunoassays. The average plasma concentration of F(VII)t, in sickle cell plasma
      was significantly lower than that of the control subjects (0.70 +/- 0.19 U/ml
      versus 1.16 +/- 0.41 U/ml), whereas F(VII)z in the patients and controls were
      0.47 +/- 0.15 U/ml and 1.15 +/- 0.33 U/ml respectively, P < 0.001. Both measures
      of factor VII suggest a higher factor VII turnover in sickle cell disease. The
      mean concentration of TAT in the plasma of HbSS patients were significantly
      higher than those of HbAA controls (371 +/- 44 pM versus 42 +/- 2 pM) (P <
      0.001), a difference that is strongly indicative of higher rates of in vivo
      thrombin generation by HbSS patients. Plasmas of HbSS patients had significantly
      higher concentrations of FPA compared to those of the control subjects (12.85 +/-
      1.96 ng/ml versus 4.22 +/- 0.37 ng/ml) (P < 0.001). The D-dimer levels were also
      higher in the HbSS than control plasmas (1029.6 +/- 58.6 ng/ml versus 224.3 +/-
      27.6 g/ml) (P < 0.001), with the patients' values being indicative of enhanced
      fibrinolysis. These results strongly suggest accelerated in vivo coagulation and
      fibrinolysis in HbSS patients even during steady state. They are consistent with
      the hypothesis that haemostasis is less tightly regulated in the HbSS patients
      than in HbAA controls. The altered regulation of haemostasis may contribute to
      the initiation of vaso-occlusive processes associated with sickle cell painful
      episodes.

PMID- 1390245
TI  - A prospective study to determine the safety of omitting the antiglobulin
      crossmatch from pretransfusion testing.
AB  - Transfusion medicine laboratories routinely perform a series of pretransfusion
      serological tests including: ABO grouping, Rh typing, and investigation of the
      recipient's serum to detect antibodies against blood group antigens (antibody
      screen). As a final check, most laboratories also perform a crossmatch in which
      the recipient's serum is incubated with the donor's red cells followed by the
      addition of an antiglobulin reagent (antiglobulin crossmatch). The need for the
      antiglobulin crossmatch when the antibody screen is negative has been questioned
      because there are few antibodies that are detected by this test. Such antibodies
      are usually directed against low incidence antigens that are not expressed on the
      screening cells and in many cases the clinical importance of these antibodies is
      uncertain. For these reasons, we performed a prospective study in which patients
      requiring red cell transfusion had a group and screen performed. If the antibody
      screen was negative the antiglobulin crossmatch was omitted. Following the
      transfusion of the blood, the antiglobulin crossmatch was performed to look for
      any potential incompatibility. All patients were monitored both serologically and
      clinically. Over the 2-year interval of the study 9128 patients were entered.
      There were 8936 patients (97.9%) with a negative antibody screen and 26.9% (2404
      patients) were transfused a total of 10,899 red cell concentrates. The
      antiglobulin crossmatch performed after the transfusion indicated that 168 red
      cell concentrates (1.5%) would have been incompatible if the antiglobulin
      crossmatch had been performed pretransfusion. These 168 red cell concentrates
      were transfused to 119 patients during 130 transfusion episodes (defined as all
      transfusions administered within 24 h). Of the 130 transfusion episodes, 79.2%
      (103/130) were false positive laboratory results. There were 27 transfusion
      episodes where the antiglobulin crossmatch on blood transfused was positive due
      to an IgG antibody. Even though these transfused red cell concentrates were
      designated incompatible by the antiglobulin crossmatch, none of the patients
      receiving this blood had clinical or serological evidence of haemolysis. We
      concluded that the antiglobulin phase of the crossmatch can be omitted from
      pretransfusion testing without putting patients at risk.

PMID- 1390244
TI  - PCR analysis of HIV-1 sequences and differential immunological features in
      seronegative and seropositive haemophiliacs.
AB  - We have compared the immunological features of two matched groups of seronegative
      and seropositive haemophilia A individuals. Both groups were exposed from 1981 to
      1985 to comparable amounts and batches of FVIII concentrates not subjected to
      virus inactivation procedures, and had therefore a 100% probability of receiving
      HIV-contaminated material. The presence of proviral HIV-1 sequences was evaluated
      by PCR in the DNA from peripheral blood lymphocytes and/or monocytes. After
      hybridization with specific probes, DNA from all seropositive haemophiliacs
      revealed HIV sequences; no HIV sequences were observed from the DNA of
      seronegative patients, even after two rounds of amplification, thus suggesting
      that these patients were not affected by a latent HIV infection. Seronegative/PCR
      and seropositive/PCR+ patients showed a normal and reduced number of CD4+
      lymphocytes, and a slight and marked increase of CD8+ cells respectively.
      Activated T cells expressing the HLA-DR antigen were elevated in both groups.
      Interestingly, a significant reduction of circulating CD56+/CD3- NK lymphocytes
      was observed only in seropositive haemophiliacs, whereas NK lymphocytes with
      CD56+/CD3+ phenotype were within normal levels in both groups. In seropositive
      patients no correlation was found between the number of CD4+ and CD56+/CD3-
      lymphocytes. The marked reduction of CD56+/CD3- lymphocytes observed in
      seropositive haemophiliacs in addition to the CD4+ cell depletion may represent a
      key pathogenetic factor which facilitates the onset and/or the progression of HIV
      1 infection in haemophiliacs, and is related to the capacity of HIV to infect NK
      cells.

PMID- 1390246
TI  - Amino acid metabolism during platelet storage for transfusion.
AB  - Previous studies indicated that the concentration of ammonia rises during storage
      of platelet concentrates (PC) at 22 degrees C for transfusion and that fuels
      other than glucose are important for metabolism. Therefore, in the current study,
      we measured the concentrations of 17 plasma amino acids during PC storage; 16 of
      these either rose or were unchanged while the concentration of glutamine fell to
      zero by day 4. As the concentration of glutamine fell, the concentration of
      glutamate rose with a relationship suggesting that 65-75% of the glutamine was
      metabolized no further than glutamate. Phosphate-dependent glutaminase activity
      was present in platelets at 22.3 +/- 6.3 nmol/min/mg protein, a level similar to
      that seen in lymphocytes and macrophages. Leucodepletion studies excluded a
      significant contribution of contaminating leucocytes to these measurements.
      Thrombin stimulation did not increase the rate of glutamine metabolism. Analysis
      of the rates of glutamine metabolism suggests that it accounts for most of the
      ammonia produced during PC storage. However, it appears to be relatively
      insignificant as a metabolic fuel. The role of glutamine metabolism for platelets
      is uncertain. It may be a vestige of a pathway in the megakaryocyte. The ammonia
      which it produces may be deleterious for platelets and for patients with liver
      disease who receive PC infusions.

PMID- 1390247
TI  - Red blood cells from patients with sickle cell disease exhibit an increased
      adherence to cultured endothelium pretreated with tumour necrosis factor (TNF).
AB  - Red blood cells (RBCs) from 24 patients with sickle cell disease were more
      adherent to cultured endothelium pretreated with the inflammatory cytokine,
      tumour necrosis factor (TNF) than RBCs from 22 healthy subjects. The enhanced
      sticking was apparent in RBC preparations from patients who were in crisis (mean
      190% increase from controls) and out of crisis (mean 220% increase) and was not
      related to the number of circulating RBCs, reticulocytes, platelets, leucocytes
      or haemoglobin levels. When irreversibly sickled RBCs, enriched by centrifugation
      on density gradients, were added to TNF-treated endothelium they were found to be
      significantly more adherent (mean 411% increase; P < 0.001) than the
      unfractionated RBCs from the same patients. There was no difference between the
      adherent properties of sickle RBCs and normal RBCs for untreated endothelium.
      Contributing factors to the enhanced adhesion to TNF-treated endothelium may be
      the low surface change of sickle RBCs, and increased levels of fibrinogen and von
      Willebrand's factor (vWF) in the patients' plasma. By acting on vascular
      endothelium to increase its adhesiveness for sickled RBCs, it is concluded that
      inflammatory cytokines such as TNF may have a prominent role in mediating the
      events that lead to microvascular occlusions in sickle cell disease.

PMID- 1390248
TI  - Rheological changes in the prodromal and established phases of sickle cell vaso
      occlusive crisis.
AB  - A rheological study has been made in 20 patients with sickle cell anaemia in the
      steady state and in the prodromal and established phases of 12 vaso-occlusive
      crises. Rheology of sickle cells was studied by discontinuous density gradient
      fractionation and by filtration through pores of 5 microns diameter. The
      prodromal phase of crisis (day 1), when compared with mean steady state values,
      was associated with the development of a sub-population of poorly deformable
      dense cells. This sub-population appeared 1 or more days before the acute-phase
      rise in C-reactive protein, orosomucoid, fibrinogen, plasma viscosity and
      leucocytes, and before the rise in serum lactate dehydrogenase. As crisis
      evolved, the sub-population decreased to steady-state values, or below, by days 6
      7. Identification of the prodromal phase of sickle cell crisis has allowed the
      detection of rheological changes of potential aetiological significance.

PMID- 1390249
TI  - Serum erythropoietin in the diagnosis of polycythaemia and after phlebotomy
      treatment.
AB  - Serum erythropoietin (S-Epo) was measured with a radiommunoassay method in 36
      patients with polycythaemia vera, 17 patients with secondary polycythaemia and 14
      patients with relative polycythaemia. The diagnoses were made without the aid of
      the S-Epo values. It was found that S-Epo was below the reference range in 34/36
      patients with polycythaemia vera (mean 2.1 +/- 1.0 U/l), elevated in all cases of
      secondary polycythaemia (mean 121.7 +/- 242 U/l) and normal in all but one of the
      cases with relative polycythaemia (mean 7.0 +/- 2.5 U/l). Previous studies of S
      Epo levels in the differential diagnosis of polycythaemia have shown significant
      differences between the means of the groups but a considerable overlap. After
      phlebotomy treatment to normal haematocrit levels, the S-Epo levels remained
      subnormal in most of the polycythaemia vera patients even after 18 months at a
      haematocrit around 45%. Two patients who had been kept at normal haematocrit for
      6 and 7 years both had subnormal S-Epo. We conclude that with an Epo assay method
      of high sensitivity and specificity it is possible to differentiate between
      different forms of polycythaemia with a high degree of certainty, even between
      patients with relative polycythaemia and polycythaemia vera patients. The reason
      why S-Epo remains low in spite of a normal haematocrit in treated polycythaemia
      vera patients is not known.

PMID- 1390250
TI  - The beta-thalassaemia mutations in the population of Cyprus.
AB  - We have identified the beta-thalassaemia alleles in nearly all known Turkish
      Cypriot beta-thalassaemia homozygotes and in over 700 Greek Cypriot beta
      thalassaemia heterozygotes living on the island of Cyprus. The data confirmed
      earlier observations that the IVS-I-100 (G-->A) mutation is present for about 74
      80%, while three other alleles [IVS-II-745 (C-->G), IVS-I-6 (T-->C), IVS-I-1 (G-
      >A)] occur at frequencies of 5-8%. Nearly identical percentages were observed for
      the two Cypriot groups, quite different from those for beta-thalassaemia patients
      from Greece and Turkey. This suggests close contacts between the two Cypriot
      communities during many centuries without a major recent influence from Greek or
      Turkish beta-thalassaemia carriers.

PMID- 1390252
TI  - Pyridoxal 5-phosphate therapy in a patient with myelodysplastic syndrome and
      adult onset congenital erythropoietic porphyria.

PMID- 1390251
TI  - Subcutaneous injection of factor IX for the treatment of haemophilia B.
AB  - Haemophilia B patients are normally treated, either prophylactically or in
      response to bleeding episodes, by frequent intravenous injections of factor IX
      purified from blood donors. Here we show in model animal experiments that
      purified human factor IX, when injected subcutaneously, is rapidly (in 3-11 h)
      and reasonably efficiently (30-40% of an equivalent intravenous dose) transported
      at least partly by the lymphatic drainage of the skin into the bloodstream,
      mostly in a biologically active form. This suggests that patients could be
      treated prophylactically by subcutaneous rather than intravenous injection, where
      the short delay in raising plasma factor IX to haemostatic levels would be
      clinically acceptable. More generally, our studies emphasize that the
      subcutaneous route of injection should be useful for other therapeutic proteins,
      including other clotting factors, which have to be delivered to the bloodstream,
      as long as their half-life is at least a few hours allowing time for transport
      into the general circulation.

PMID- 1390253
TI  - Type I Padua: a new variant of von Willebrand's disease.

PMID- 1390254
TI  - Acquired von Willebrand's disease due to excessive fibrinolysis.

PMID- 1390255
TI  - t(14;18) and bcl-2 gene rearrangement in a B-chronic lymphocytic leukaemia.

PMID- 1390256
TI  - Multilobulated, multinucleated multiple myeloma.

PMID- 1390257
TI  - Constitution and behaviour of the spherocyte membrane.

PMID- 1390259
TI  - Megadose methylprednisolone for pure red cell aplasia.

PMID- 1390258
TI  - Infusion of clotting factor concentrates in haemophilia.

PMID- 1390260
TI  - Clinical study on determination of serum oestradiol in chronic idiopathic
      thrombocytopenic purpura.

PMID- 1390261
TI  - Granular lymphocyte leukaemia with multiple myeloma.

PMID- 1390262
TI  - Therapy with human recombinant erythropoietin in patients with myelodysplastic
      syndromes.

PMID- 1390263
TI  - Serum erythropoietin levels during haematinic therapy.

PMID- 1390264
TI  - The carcinogenic effect of exposure to low doses of carcinogens.

PMID- 1390265
TI  - Low dose exposure to natural and man made fibres and the risk of cancer: towards
      a collaborative European epidemiology. Report of a workshop held in Paris , 10-12
      June, 1991.

PMID- 1390266
TI  - Hazards of closed pesticide mixing and loading systems: the paradox of protective
      technology in the Third World.
AB  - In studies in developing countries, closed systems for mechanically mixing and
      loading hazardous pesticides have been shown to reduce exposure to workers. To
      evaluate the efficacy of closed systems in preventing worker exposure in the
      developing world, a cross sectional study was conducted at rural crop dusting
      airports in the cotton growing region of Nicaragua. Worker exposure was evaluated
      by measuring the activity of erythrocyte cholinesterase in the field with a new
      design battery operated colorimeter. The 10 mixer loaders at four airstrips with
      closed systems were compared with the 16 mixer loaders at four airstrips where
      pesticides were hand poured. Paradoxically, cholinesterase activity was 1.1 IU/ml
      blood (95% Cl 0.49-1.8) lower (inhibited) among workers in airstrips with closed
      systems than among workers hand pouring insecticides, after adjusting for weight
      of organophosphates sprayed in the past 14 days, and for prior training in safe
      use of pesticides. Mixer loaders with prior training had cholinesterase activity
      0.83 IU (95% Cl 0.30-1.4) higher than untrained workers, and the weight of
      organophosphates sprayed was also a statistically significant predictor in the
      model. Unfortunately, management viewed the closed systems primarily as a
      production tool, rather than as a way to protect workers. Airstrips with closed
      systems were able to apply an average of 3250 lb organophosphates per worker in
      the 14 days before the survey compared with 849 lb per worker in airstrips
      without closed systems. Only three of 10 mixer-loaders at airstrips with closed
      systems had received formal training in safer use of pesticides. Because of
      shortage of personnel and transport, it was difficult for the responsible
      government agencies to train workers adequately and to enforce pesticide health
      and safety standards at multiple dispersed worksites.

PMID- 1390267
TI  - Occupational and non-occupational hepatitis B virus infection among hospital
      employees in Jerusalem: a basis for immunisation strategy.
AB  - The present study was designed to assess the risk of hepatitis B virus (HBV)
      infection among hospital employees, who often contract the infection before the
      beginning of their employment, and to suggest a prevention strategy. The study
      population consisted of 2518 subjects working or studying at the two Hadassah
      University hospitals, on Mount Scopus and at Ein Kerem in Jerusalem. The total
      prevalence for anti-HBc positivity as an indicator for past or present HBV
      infection was 17.6%. Several variables, including country of birth, age, and
      duration of employment significantly affected the rate of anti-HBc positivity.
      The highest rates for anti-HBc+ were found in personnel of selected departments
      such as haemodialysis (31.8%), haematology/oncology (28.3%), and the blood bank
      (24.0%), after adjustment for country of birth, age, and sex. Specific
      occupations in the hospital were associated with an increased rate of anti-HBc
      positivity. Thus the highest rate of HBV infection (after adjustment for country
      of birth, age, and sex) was shown for housekeepers (32.4%) and departmental
      secretaries (23.6%), who take care of waste products containing blood, or who
      transfer vials containing blood to the hospital laboratories. By comparison, anti
      HBc was positive in 17.2% of nurses, 15.6% of physicians, and only 7.8% of
      administrative clerks. Israel is a country of immigration, and anti-HBc rates
      were four times higher in employees born in countries where HBV is more endemic-
      for example, in north Africa and Mediterranean countries--than in employees born
      in western Europe or the United States. However, rate of anti-HBc + increased
      significantly with age as well as duration of employment in the hospital,
      irrespective of country of birth. These data indicate that although HBV infection
      often occurs in Israel before commencement of employment in the hospital,
      hospital employees are at significant risk for contracting HBV infection during
      their professional lifetime regardless of where they were born. Moreover,
      paramedical personnel such as housekeepers and departmental secretaries are in
      the highest risk group for contracting HBV. Finally, as a result of the high
      background of anti-HBC positivity in selected ethnic groups, mandatory screening
      for anti-HBc before employment in medical institutions in Israel is recommended
      for them, then active vaccination against HBV for employees at risk. Employees
      who immigrated from western Europe and the United States should be immunised
      without pre-vaccination screening for HBV.

PMID- 1390268
TI  - Histological type of lung carcinoma in asbestos cement workers and matched
      controls.
AB  - Histological types of lung carcinoma were examined in a case series of workers
      exposed to asbestos cement dust (n = 29) and matched controls (n = 87). The
      proportion of adenocarcinomas was 31% among the exposed subjects and 15% among
      the controls (mid-p = 0.05). Among workers with high exposure the proportion of
      adenocarcinoma was even higher (45%, 5/11; mid-p = 0.03). The proportion of
      peripheral tumours tended to be higher among exposed cases than controls (24 v
      12%, mid-p = 0.12). Lobe of origin did not differ, however, between exposed cases
      and controls. Thus the study indicates an association between the degree of
      exposure to asbestos and adenocarcinoma of the lung, and a peripheral rather than
      central localisation of the tumours, but with virtually the same distribution of
      lobe of origin as in the general population.

PMID- 1390270
TI  - Influence of the degree of exposure to lead on relations between alcohol
      consumption and the biological indices of lead exposure: epidemiological study in
      a lead acid battery factory.
AB  - Alcohol has been shown to interact with lead to influence haem biosynthesis. The
      aim of this study was to define the dependence of this interaction on the degree
      of exposure to lead. Exposure to alcohol was estimated by measurement of alcohol
      concentrations in a sample of urine collected during the morning (AlcUM) (0.82
      (SD 4.36) mmol/l) and in a sample collected during the afternoon (AlcUA) (1.15
      (SD 3.49) mmol/l). The biological monitoring of exposure to lead included
      measurements of blood lead (Pb-B) (1.82 (SD 0.72) mumol/l), urinary delta
      aminolaevulinic acid (ALAU) (35.33 (SD 28.00) mumol/l; d = 1.015), and
      erythrocyte zinc-protoporphyrin (ZPP) (112.90 (SD 83.71) nmol/mmol Hb)
      concentrations. The study of the influence of the degree of occupational exposure
      to lead on relations between alcohol consumption and effects of the exposure to
      lead led to the consideration of two different groups--namely, mildly and
      strongly exposed subjects. In the first group, individual biological
      susceptibility seemed to play a preponderant part. In the second, the pool of
      lead present in the body seemed to be sufficiently important to mask the effects
      of individual susceptibility.

PMID- 1390269
TI  - In vivo measurements of lead in bone at four anatomical sites: long term
      occupational and consequent endogenous exposure.
AB  - Measurements of bone lead concentrations in the tibia, wrist, sternum, and
      calcaneus were performed in vivo by x ray fluorescence on active and retired lead
      workers from two acid battery factories, office personnel in the two factories
      under study, and control subjects. Altogether 171 persons were included. Lead
      concentrations in the tibia and ulna (representative of cortical bone) appeared
      to behave similarly with respect to time but the ulnar measurement was much less
      precise. In an analogous fashion, lead in the calcaneus and sternum
      (representative of trabecular bone) behaved in the same way, but sternal
      measurement was less precise. Groups occupationally exposed to lead were well
      separated from the office workers and the controls on the basis of calculated
      skeletal lead burdens, whereas the differences in blood lead concentrations were
      not as great, suggesting that the use of concentrations of lead in blood might
      seriously underestimate lead body burden. The exposures encountered in the study
      were modest, however. The mean blood lead value among active lead workers was
      1.45 mumol l-1 and the mean tibial lead concentration 21.1 micrograms (g bone
      mineral)-1. The kinetics of lead in the tibia appeared to be noticeably different
      from that in the calcaneus. Tibial lead concentration increased consistently both
      as a function of intensity of exposure and of duration of exposure. Calcaneal
      lead concentration, by contrast, was strongly dependent on the intensity rather
      than duration of exposure. This indicated that the biological half life of lead
      in calcaneus was less than the seven to eight year periods into which the
      duration of exposure was split. Findings for retired workers clearly showed that
      endogenous exposure to lead arising from skeletal burdens accumulated over a
      working lifetime can easily produce the dominant contribution to systemic lead
      concentrations once occupational exposure has ceased.

PMID- 1390271
TI  - Biological monitoring of exposure to nerve agents.
AB  - Changes in acetylcholinesterase activity in blood and some organs of rats after
      intoxication with sarin, soman, VX, and 2-dimethylaminoethyl-(dimethylamido)
      phosphonofluoridate (GV), in doses of roughly 2 x LD50 given intramuscularly,
      were obtained from published data and by experiment. The time course of
      inhibition of acetylcholinesterase in blood, regions of brain, and diaphragm and
      the occurrence of signs and symptoms of poisoning (none, salivation, disturbed
      ventilation and fasciculations, convulsions, or death) were summarised and
      compared. When blood enzyme activities were 70-100% normal, no obvious signs were
      seen; at 60-70%, salivation occurred; at less than 30-55%, disturbed ventilation
      and fasciculations were seen, and at 15-30%, convulsions occurred. Less than 10%
      was fatal. In experiments with narcotised dogs, the blood acetylcholinesterase
      activity and the ability to reactivate it with trimedoxime were determined after
      intoxication by intramuscular administration of the four compounds. It is
      concluded that acetylcholinesterase activity in the blood corresponds to that in
      the target organs and can be considered as an appropriate parameter for
      biological monitoring of exposure to nerve gases. Moreover, determination of
      reactivation of blood acetylcholinesterase gives more information than simple
      determination of enzyme activity.

PMID- 1390272
TI  - Biological monitoring of workers exposed to acetone in acetate fibre plants.
AB  - Concentrations of acetone in urine, alveolar air, and blood were measured by gas
      chromatography with flame ionisation detection for 110 subjects occupationally
      exposed to acetone (mean 372 ppm) in three factories. Significant relations were
      found between the time weighted average environmental concentration and the
      concentration in the biological samples. The strongest correlation was between
      the concentration of acetone in urine and the degree of exposure (r = 0.71, 95%
      CI 0.64-0.77). This suggests that urinary acetone concentration is the best
      biological index of occupational exposure to acetone.

PMID- 1390273
TI  - Blood concentration of carbon disulphide in "normal" subjects and in alcoholic
      subjects treated with disulfiram.
AB  - Assay of free and acid labile carbon disulphide (free and total CS2 respectively)
      in human blood was performed by gas chromatography/spectrometry. The method used
      a large dynamic head space volume and a "cryogenic trap". Blood CS2 concentration
      was measured in 42 subjects not occupationally exposed to CS2 (group A) and in 11
      alcoholic subjects (group B) treated with disulfiram. Free CS2 concentration
      showed a mean value of 261 ng/l in the 42 subjects in group A and 9482 ng/l in
      eight subjects of group B. Total CS2 concentration was 897 ng/l and 40,084 ng/l
      in groups A and B respectively. Differences between the groups were highly
      significant for concentrations of both free and total CS2. Total CS2
      concentration was about four times as high as free CS2 concentration in both
      groups. A significant correlation was found between free and total CS2
      concentration both in group A and in group B. In the alcoholic subjects (group
      B), blood concentrations of both free and total CS2 were related to time of
      sampling after treatment with disulfiram.

PMID- 1390275
TI  - Postpartum changes to maternal blood lead concentrations.

PMID- 1390274
TI  - Mortality among firefighters from three northwestern United States cities.
AB  - To explore whether exposure among firefighters to fire smoke could lead to an
      increased risk of cancer, lung disease, and heart disease, the mortality of 4546
      firefighters who were employed by the cities of Seattle and Tacoma, WA and
      Portland, OR for at least one year between 1944 and 1979 were compared with
      United States national mortalities and with mortality of police officers from the
      same cities. Between 1945 and 1989, 1169 deaths occurred in the study population
      and 1162 death certificates (99%) were collected. Mortality due to all causes,
      ischaemic heart disease, and most other non-malignant diseases was less than
      expected based upon United States rates for white men. There was no excess risk
      of overall mortality from cancer but excesses of brain tumours (standardised
      mortality ratio (SMR) = 2.09, 95% confidence interval (95% CI) 1.3-3.2) and
      lymphatic and haematopoietic cancers (SMR = 1.31, 95% CI = 0.9-1.8) were found.
      Younger firefighters (< 40 years of age) appeared to have an excess risk of
      cancer (SMR = 1.45, 95% CI 0.8-2.39), primarily due to brain cancer (SMR = 3.75,
      95% CI 1.2-8.7). The risk of lymphatic and haematopoietic cancers was greatest
      for men with at least 30 years of exposed employment (SMR = 2.05, 95% CI 1.1
      3.6), especially for leukaemia (SMR = 2.60, 95% CI 1.0-5.4).

PMID- 1390276
TI  - An industrial disease.

PMID- 1390277
TI  - Antiestrogen-liganded estrogen receptor interaction with estrogen responsive
      element DNA in vitro.
AB  - The mechanism whereby antiestrogens alter the ability of the estrogen receptor
      (ER) to enhance transcription of estrogen-regulated genes is largely unknown. The
      effect that selected estrogenic and antiestrogenic ligands have on binding of ER
      to specific DNA sequences, estrogen responsive elements (EREs) has been
      quantitated. No differences in purification properties of calf uterine ER
      liganded with 4-hydroxytamoxifen (4-OHT-ER), ICI 164,384 (ICI 164,384-ER) or
      estradiol (E2-ER) were detected. A microtiter well plate assay was employed in
      which liganded ER bound to plasmid DNA is preferentially retained compared to
      free liganded ER. Binding of E2-ER, 4-OHT-ER, or ICI 164,384-ER was measured to
      plasmids containing or lacking a 38bp consensus ERE in vitro. The EREs tested
      contain an inverted repeat (5'-CAGGTCAGAGTGACCTG-3'). Both E2-ER and 4-OHT-ER
      showed similar high affinity specific binding (Kd = 0.24 and 0.16 nM,
      respectively) to one copy of the ERE. ICI 164,384-ER did not bind to plasmids
      containing one ERE. At saturation, however, 4-OHT-ER binding was about 50% of
      that observed for E2-ER. When the plasmid contained 3 or 4 tandem copies of the
      ERE, binding of E2-ER, 4-OHT-ER, and ICI 164,384-ER binding was measurable. E2-ER
      bound in a cooperative manner as suggested by convex Scatchard plots and Hill
      coefficients > 1.5. In contrast, 4-OHT-ER binding displayed much reduced
      cooperativity, and ICI 164,384-ER did not display cooperative binding. From these
      results, we propose that the conformation of ER induced by 4-OHT reduces its
      binding capacity to this consensus ERE without altering its affinity of binding.
      Furthermore, higher order protein-protein interactions between antiestrogen
      liganded ER bound to DNA differ from those of E2-ER bound to ERE.

PMID- 1390278
TI  - Effects of retinoic acid on estrogen- and thyroid hormone-induced growth in a
      newly established rat pituitary tumor cell line.
AB  - In order to elucidate the complex mechanism(s) of action of steroid hormones,
      thyroid hormone and retinoic acid in pituitary mammotrophs, a clonal cell line
      (G3) was isolated from the rat pituitary tumor MtT/F84. G3 cells were found to
      secrete prolactin constitutively and to contain receptors for estrogen,
      glucocorticoid, progesterone and thyroid hormone. Stimulation of G3 cells with
      thyroid hormone resulted in a modest but significant increase in estrogen and
      progesterone receptor levels, however, retinoic acid treatment had no effect.
      Simultaneous addition of thyroid hormone and estrogen showed an additive effect
      on progesterone receptor levels in G3 cells. Thyroid hormone as well as estrogen
      enhanced the growth of G3 cells. Interestingly, retinoic acid was also found to
      enhance their growth but its enhancement was less potent than thyroid hormone and
      estrogen. Low concentrations of estradiol and thyroid hormone showed additive
      effects, but G3 cells stimulated with high concentrations of thyroid hormone
      failed to elicit an additive effect with estrogen, suggesting the presence of a
      common pathway in the growth-stimulatory actions of these hormones. In addition,
      exposure of G3 cells to retinoic acid completely abolished the effects of
      estrogen or thyroid hormone in terms of cell growth. These results suggest that
      there are complex interactions in the signalling pathways for estrogen, thyroid
      hormone and retinoic acid action in G3 cells.

PMID- 1390279
TI  - In vitro potency and selectivity of the non-steroidal androgen aromatase
      inhibitor CGS 16949A compared to steroidal inhibitors in the brain.
AB  - A sensitive in vitro 3H2O microassay for aromatase activity was used to evaluate
      the potency and selectivity of three aromatase inhibitors in mammalian (gerbil)
      and avian (ring dove) hypothalamus. The steroidal inhibitors, 1,4,6-androstatrien
      3,17-dione (ATD) and 4-hydroxy-androstenedione (4-OH-A) were compared with a new
      non-steroidal imidazole inhibitor, CGS 16949A [4-(5,6,7,8-tetrahydroimidazo-[1,5
      a]-pyridin-5-yl)benzonitrile HCl]. Adult male dove hypothalamic aromatase is
      highly active [Vmax = 5.3 pmol testosterone (T) converted/h/mg protein], has high
      substrate binding affinity (Km = 4.0 nM), and direct involvement in control of
      sexual behaviour. With [1 beta-3H]T or [1 beta-3H]A as substrate, male dove
      preoptic aromatase activity was inhibited more effectively and selectively by CGS
      16949A. Thus, Kis and IC50s for aromatization were approximately 50 times lower
      for the non-steroidal inhibitor, and inhibition of the other major androgen
      metabolizing enzymes (5 alpha/beta-reductase) occurred at concentrations at least
      one order of magnitude greater than for ATD and 4-OH-A. Neonatal male gerbil
      hypothalamic aromatase activity (Vmax = 1.3 pmol T converted/h/mg protein) was
      lower than in the dove. Aromatase inhibition by CGS 16949A is more potent in the
      neonatal gerbil than in the dove (Kis of 0.03 and 0.60 nM, respectively, with A
      as substrate). We conclude that the imidazole is an effective aromatase inhibitor
      in both the adult and developing brain.

PMID- 1390280
TI  - Progesterone receptor induction by danazol in cultured cancer cells and the rat
      uterus.
AB  - We have previously reported that clinical trials relating to the use of danazol
      in the management of benign breast disease show a positive correlation between
      favourable clinical response and an induction of progesterone receptors in the
      affected tissue which is maintained for a period of at least 6 months subsequent
      to the cessation of treatment. Further studies designed at elucidating more
      clearly the actions of danazol at the cellular and molecular levels have
      confirmed that progesterone receptors are down-regulated by short-term progestin
      action at the level of the mRNA transcript, but that danazol is subsequently able
      to produce an enhanced cellular response, inducing progesterone receptors in the
      presence of oestrogenic agents. Uteri from danazol-treated rats showed a doubling
      of progesterone receptor concentrations compared with the control uteri. In the
      mammary cancer cell line T-47D, cells treated with danazol had increased
      progesterone receptor concentrations of 558.4 +/- 32.0 compared with 152.6 +/-
      7.0 fmol/mg protein in the control cells. In both cases, these inductions were
      observed following a period of progesterone receptor suppression. Short-term
      molecular studies on T-47D cells indicated that progesterone and danazol
      initially inhibit mRNA transcription, but that 24 h after treatment an induction
      is observed. This is especially marked in the danazol-treated cells.

PMID- 1390281
TI  - Steroid-1-dehydrogenase of Rhodococcus erythropolis: purification and N-terminal
      amino acid sequence.
AB  - The inducible steroid-1-dehydrogenase from the bacterium Rhodococcus erythropolis
      IMET 7030 was purified to homogeneity using affinity chromatographic,
      electrophoretic, and ion exchange techniques. The spectrum of the pure enzyme is
      characterized by the associated FAD. The M(r) of the enzyme is 56,000. The amino
      acid composition and the sequence of the 13 N-terminal amino acids are given.

PMID- 1390282
TI  - Immunohistochemical detection of human estrogen receptor with region D-specific
      antipeptide antibodies.
AB  - To study the possibility of using antipeptide antibodies for the
      immunohistochemical determination of human estrogen receptors (ER), three
      peptides corresponding to the putative major antigenic regions of the human ER
      (Met12-Leu26, or ERP1; Thr227-Gln267, or ERP2; Leu256-Gly275, or ERP3) were used
      to produce site-specific rabbit polyclonal antipeptide antisera. High titer
      antibodies were obtained against all the peptides used, as judged by time
      resolved fluoroimmunoassay. The antibodies against region D (ERP3) specifically
      immunoprecipitated the ER proteins in vitro, as did the antiERP2 antibodies to a
      much smaller extent. With one of the region D-specific antibodies (antiERP3 Ab2)
      ER could also be immunohistochemically detected. When benign and malignant human
      breast and normal endometrial tissues were used, the immunohistochemical staining
      observed with these antipeptide antibodies correlated well with the staining
      obtained with an established method. Thus, the results reported here show that
      this part of region D in ER is a potential antigenic epitope for the production
      of site-specific antibodies against ER. Antipeptide antibodies produced against
      this region can be used to immunolocalize the ER in various normal and
      pathological human tissues.

PMID- 1390283
TI  - Comparison of human fetal hepatic and adrenal cytochrome P450 activities with
      some major gestational steroids and ethylmorphine as substrates.
AB  - The immunoidentified human fetal liver and adrenal microsomal contents of
      cytochromes P450IIIA and P450XVIIA1 were compared to the metabolism of steroids
      and ethylmorphine. In fetal liver microsomes, 16 alpha-hydroxylation of
      dehydroepiandrosterone (DHA) was catalyzed at a high rate in almost all
      investigated specimens and accompanied by a high ethylmorphine N-demethylase
      activity. Progesterone 16 alpha- and 17 alpha-hydroxylation was found only in the
      livers with the highest DHA 16 alpha-hydroxylation activities, while 21
      hydroxylation of progesterone was catalyzed only occasionally in these samples.
      In fetal adrenal microsomes, 21-hydroxylation of progesterone to 11
      desoxycorticosterone (DOC) and 11-desoxycortisol (DOCOL) was catalyzed. In
      contrast to fetal liver, the adrenals also catalyzed the 17 alpha-hydroxylation
      of pregnenolone and the formation of DHA from 17 alpha-OH-pregnenolone. 16 alpha
      hydroxylation of DHA and ethylmorphine N-demethylation were modest in the
      adrenals. P450IIIA/HLp was immunoidentified in all investigated liver specimens
      except two (18/20) in which no ethylmorphine N-demethylation or 16 alpha
      hydroxylation of DHA was found. P450XVIIA1 bands were observed in 8/20 blots of
      liver specimens, but there was no correlation between the density of these bands
      and the 17 alpha-hydroxylation of progesterone. All 11 fetal adrenal samples
      catalyzed DHA 16 alpha-hydroxylation, although only 8 were positive for
      P450IIIA/HLp. All investigated adrenals were positive in regard of the P450XVIIA1
      band, except one (8/9) with a low 17 alpha-hydroxylation of progesterone. All
      adrenal specimens catalyzed 21-hydroxylation of progesterone and contained
      P450C21 bands in immunoblots and all samples catalyzed the formation of DOC and
      DOCOL from progesterone. Our findings in the fetal livers show a correlation
      between the DHA 16 alpha-hydroxylation and immunoidentified P450IIIA/HLp bands.
      In adrenals, there was a correlation between the immunoidentified P450XVIIA1
      bands and the 17 alpha-hydroxylation of progesterone.

PMID- 1390284
TI  - Purification and properties of human hepatic 3 alpha-hydroxysteroid
      dehydrogenase.
AB  - 3 alpha-Hydroxysteroid dehydrogenase (3 alpha-HSD) was purified greater than 500
      fold from human liver cytosol. The purification was monitored using 5 beta
      [3H]dihydrocortisol (5 beta-DHF) as substrate. Electrophoretically homogeneous
      enzyme was obtained using a procedure that involved ammonium sulfate
      precipitation and three successive column chromatography steps: DEAE-cellulose,
      hydroxylapatite and Blue-Sepharose. The enzyme is a monomer since the native
      molecular weight was found to be 37,000, using a calibrated Sephadex G-75 column,
      and the denatured subunit molecular weight was determined to be 38,500, by
      polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The enzyme had a pI
      of 5.6-5.9. The 3-ketosteroids: cortisol, testosterone, progesterone and
      androstenedione, were not substrates for 3 alpha-HSD indicating that a saturated
      4,5 double bond was required for substrate activity. The conformation at the 5
      position, however, did not influence substrate activity since 5 alpha- and 5 beta
      DHF and 5 alpha-dihydrotestosterone were all reduced at similar rates. The
      purified enzyme preferred NADPH to NADH as a cofactor and showed a broad peak of
      activity in the pH range of 6.8-7.4. The apparent Km for 5 beta-DHF was 18
      microM. The enzyme was markedly stabilized by 50 mM phosphate buffer containing
      10 to 20% glycerol at 4 degrees C. Freezing and thawing of the enzyme resulted in
      a large loss of activity during early stages of the purification. This is the
      first report of the purification to homogeneity of 3 alpha-HSD from human tissue.

PMID- 1390286
TI  - Proceedings of the XV meeting of the International Study Group for Steroid
      Hormones. Rome, Italy, 28-30 November 1991.

PMID- 1390285
TI  - Actions of acetyl-L-carnitine on the hypothalamo-pituitary-gonadal system in
      female rats.
AB  - Acetyl-L-carnitine (ALC) is known to affect several aspects of neuronal activity.
      To evaluate the neuroendocrine actions of this compound, several endocrinological
      parameters were followed in ALC-treated and control animals during recovery from
      dark-induced anestrus. In treated animals, serum luteinizing hormone (LH) and
      prolactin levels were higher than those of controls during the proestrous and
      estrous phases of the cycle, and serum estradiol levels were higher during
      estrus. No significant changes were observed in serum levels of follicle
      stimulating hormone and progesterone. Uterine weight was increased in ALC-treated
      rats during proestrus and estrus, but not in diestrus. The basal release of
      gonadotropin-releasing hormone (GnRH) from perifused hypothalamic slices of ALC
      treated animals was elevated at proestrus and diestrus, and GnRH release elicited
      by high K+ was higher during all three phases of the cycle. The basal release of
      LH from perifused pituitaries of treated animals was elevated in diestrus, and
      the LH response to GnRH was higher in estrus and diestrus I. Depolarization with
      K+ caused increased LH secretion during proestrus and estrus in treated animals.
      In contrast to these effects of ALC treatment in vivo, no direct effects of ALC
      were observed during short- or long-term treatment of cultured pituitary cells.
      These results indicate that ALC treatment influences hypothalamo-pituitary
      function in a cycle stage-dependent manner, and increases the secretory activity
      of gonadotrophs and lactotrophs. Since no effects of ALC on basal and agonist
      induced secretory responses of gonadotrophs were observed in vitro, it is
      probable that its effects on gonadotropin release are related to enhancement of
      GnRH neuronal function in the hypothalamus.

PMID- 1390287
TI  - Familial and iatrogenic cortisol receptor resistance.
AB  - Primary cortisol receptor resistance has been reported in 6 patients and 14
      asymptomatic family members. We observed an additional 6 patients (2 males and 4
      females). The male patients presented with hypertension. The female patients
      presented with acne, hirsutism and irregular menstruations. Dexamethasone therapy
      (1-1.5 mg/day) was of considerable clinical benefit. All 6 patients showed
      insufficient suppression of cortisol after 1 mg dexamethasone. The diurnal rhythm
      of ACTH and cortisol was intact, albeit at an elevated level. There was a normal
      increase of ACTH, cortisol, and GH to insulin-induced hypoglycemia, while
      cortisol production was (slightly) elevated. Adrenal androgen levels were
      increased in all patients. Glucocorticoid receptors measured in a whole cell
      dexamethasone binding assay in mononuclear leukocytes showed a lowered affinity
      in 1, and lowered numbers of receptors in 4 patients. In 1 patient no
      abnormalities were found. As a "bioassay" for glucocorticoid action dexamethasone
      suppressibility of mitogen-stimulated incorporation of [3H]thymidine in
      mononuclear leukocytes was measured. In this last patient dexamethasone
      suppressibility of [3H]thymidine incorporation was significantly lowered. Twelve
      months' treatment with 200 mg RU 486 per day in meningioma patients induced a
      similar biochemical picture as observed in primary cortisol receptor resistance.
      Partial cortisol receptor resistance might be less rare than previously thought.
      In the 6 patients presented at least 3 different forms can be recognized. Therapy
      with dexamethasone was successful in female patients with acne and hirsutism, as
      the secondary overproduction of adrenal androgens was effectively controlled.
      Chronic therapy with RU 486 causes a biochemical picture similar to primary
      cortisol receptor resistance.

PMID- 1390288
TI  - Glucocorticoid receptors.
AB  - Glucocorticoid hormones are secreted uniquely from the zona fasciculata of the
      adrenal cortex, with marked circadian variation in basal levels and acute
      elevation in response to stress. Glucocorticoid receptors are almost ubiquitously
      distributed, and mediate a wide range of tissue-specific responses; in addition
      to classical, [3H]dexamethasone-binding GR (Type II receptors) there is excellent
      evidence that Type I sites (MR) act as mineralocorticoid receptors in some
      tissues but high affinity glucocorticoid receptors in others. Particular issues
      to be addressed in the presentation include: (i) the extent to which
      glucocorticoid receptor occupancy is modulated by extracellular (plasma-binding
      enzymes) or intracellular (proto-oncogenes) factors; (ii) whether or not there
      are specific response elements for Type I and II receptors; (iii) putative
      physiological roles for Type I, high affinity glucocorticoid receptors; (iv)
      evidence for glucocorticoid receptors other than classical GR and "MR". In
      summary, glucocorticoid receptors appear to be a final common pathway mediating
      and/or modulating circadian rhythms and stress responses. Cell-and tissue
      specificity of response to a whole-body signal is determined by local pre
      receptor, receptor and genomic differences. On the basis of previous studies on
      glucocorticoid secretion, and recent information on glucocorticoid action, it
      would at last appear possible to begin to construct a coherent physiology for
      glucocorticoid hormones.

PMID- 1390289
TI  - Glucocorticoid-dependent hypertension.
AB  - Glucocorticoid (GC) excess (Cushing's syndrome) is associated with hypertension
      in at least 70% of patients (in our series 89/130), independently of the subtype
      (pituitary or adrenal) and the duration, but not of the age of the patients.
      Cardiovascular damage is quite frequent in hypertensives, but is sometimes also
      present in normotensives. The mortality of patients with Cushing's syndrome is
      four times that of the general population when matched for age and sex, and much
      of this excess mortality is caused by cardiovascular disease. Hypertension remits
      in most of the patients after successful treatment, but may persist in some.
      Hypertension also occurs in 20% of patients treated with GC orally. The type of
      hypertension is independent of salt uptake, can not be controlled by
      spironolactone but is inhibited by a GC antagonist such as RU486. Experimentally
      induced hypertension with oral cortisol (F) is associated with a rise in cardiac
      output, a fall in calculated total peripheral resistance, an increased forearm
      vascular responsiveness to exogenous norepinephrine, but no change in overall
      sympathetic tone, or in norepinephrine reuptake. The increased pressor
      responsiveness is probably due to local postsynaptic effector mechanisms in the
      resistance vessels, which could be important in phasic increases in neuronally
      mediated constrictor responses. Both in patients with Cushing's syndrome and in
      those on chronic GC treatment, the circadian blood pressure variations are absent
      or reversed. This may contribute to the deleterious effects of the GC excess on
      blood vessels. The vascular effects of the GC may be mediated by the activation
      of specific cardiovascular receptors, by modulating vascular transport systems,
      or by altered catecholamine or prostaglandin metabolism. GC may also act as
      mineralocorticoids (MC): in fact type 1 MC receptors are unable, in vitro, to
      distinguish between aldosterone and cortisol. The specificity-conferring
      mechanism of typical target organs for MC (e.g. kidney)--is thought to be due to
      the action of local 11-beta-hydroxysteroid dehydrogenase, which converts F to
      biologically inactive cortisone (E). When the activity of the enzyme is impaired
      (syndrome of apparent MC excess, liquorice or carbenoxolone administration), F
      acts as a MC and MC-hypertension with hypokalemia occurs.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1390290
TI  - Bone and cartilage responsiveness to sex steroid hormones.
AB  - Gonadal steroids influence the skeletal growth and metabolism both during the
      pubertal growth spurt and in adulthood with aging. It is now generally agreed
      that sex steroid effect on skeletal tissues is due to indirect and direct
      actions. In this presentation, in vitro effects of sex steroids on cartilage
      cells are reported by comparison with those observed on bone cells.

PMID- 1390291
TI  - Sertoli-germ cells interactions in the human testis.
AB  - In previous histoimmunochemical studies we reported that transferrin (TF) and
      insulin-like growth factor I (IGF-I) are present in the cytoplasm of the Sertoli
      cells of the adult human testis. Receptors for TF were found mainly in adluminal
      germ cells and type I receptors for IGF-I both in Sertoli and germ cells. Using
      electron microscopy, evidence of transfer of both TF and IGF-I from the Sertoli
      to the germ cells through a receptor-mediated endocytosis mechanism was also
      found. In this paper we report the results of the histoimmunochemical
      localization of alpha inhibin in the human fetal, prepubertal and adult testis.
      In 8- to 14-week-old fetal testes a positive immunostaining was found mainly in
      the interstitial cells, whereas no staining was found in the germ cords. In the
      prepubertal testis the immunostaining was present in the Sertoli cells but not in
      the interstitial cells. In the adult human testis the immunostaining was present
      not only in the Sertoli cells but also in the spermatocytes and in several Leydig
      cells. Using electron microscopy and immunogold labeling the presence of alpha
      inhibin immunoreactivity was found in the rough endoplasmic reticulum and in the
      Golgi cisternae of both Sertoli and Leydig cells. Moreover we found evidence of
      transfer of alpha inhibin from the Sertoli to the germ cells through receptor
      mediated endocytosis.

PMID- 1390292
TI  - Steroidal and non-steroidal factors in plasma sex hormone binding globulin
      regulation.
AB  - Sex hormone binding globulin (SHBG) is a specific steroid-binding plasma
      glycoprotein regulated by several factors. Sex steroids are currently considered
      to be the main physiological regulators of this protein. SHBG levels, in fact,
      increase during estrogen treatment and decrease after androgen administration. It
      is well known, however, that in many physiological and pathological conditions
      SHBG concentrations cannot be explained only on the basis of steroidal control
      mechanisms. The regulation of SHBG levels is in fact more complex and other
      factors can also affect its plasma values. Between the steroidal factors our
      attention was focused on the role of androgens, of glandular and peripheral
      origin, in their capacity to lower SHBG plasma levels. We studied hyperandrogenic
      conditions in prepubertal (65 subjects with precocious adrenarche and 16 girls
      with prepubertal hypertrichosis, aged between 4 and 8 years) and in adult age (51
      hirsute patients aged between 14-35 years and 51 acneic patients aged between 15
      40 years). The effects of dexamethasone and ACTH administration on SHBG plasma
      levels were also evaluated. The results obtained showed that in adult
      hyperandrogenic patients SHBG levels, significantly lower than in controls, were
      not always inversely correlated with androgen levels, which, on the contrary,
      were higher than in controls. In patients with precocious adrenarche we found an
      inverse correlation only between SHBG, which was significantly lower than normal,
      and body mass index or bone age but not with androgens, suggesting that in this
      condition other factors may be more relevant than steroids in SHBG regulation.
      Between the non-steroidal factors our attention focused on insulin. We studied 40
      non-obese hyperandrogenic patients with or without ultrasonographic evidence of
      polycystic ovaries, aged 18-39 years, and 35 obese patients, aged 19-37 years,
      with or without hyperandrogenism or evidence of PCO. Low levels of SHBG were
      found not only in hyperandrogenic obese patients but also in obese patients with
      normal androgens. It is possible to conclude that (1) several factors (calorie
      intake, energy balance and growth factors), other than steroids, may be involved
      in the regulation of SHBG levels in plasma; and (2) each regulating factor may
      act to a different extent depending on the various periods of the life cycle.

PMID- 1390293
TI  - The potential relevance of cytokines to ovarian physiology.
AB  - Elucidating the secrets of intraovarian intercellular communication constitutes a
      central area of investigation. While most attention has been directed thus far at
      the somatic cellular components of the ovary, the potential role(s) and relative
      importance of the resident ovarian white blood cell have received relatively
      limited attention. Efforts are currently under way to reconcile traditional
      ovarian physiology with observations relevant to intraovarian components of the
      white blood cell series. In this connection, it is important to note that unlike
      some gonadal compartments, the ovary does not constitute an immunologically
      privileged site. Thus, resident ovarian representatives of the white blood cell
      series can be observed at various stages of the ovarian life cycle. Current
      concepts suggest that regulatory cellular networks formerly viewed in immune
      terms now fall within the broad domain of endocrinology. Viewed in this light,
      resident ovarian representatives of the white blood cell series may constitute
      potential in situ modulators of ovarian function acting in all likelihood through
      the local secretion of regulatory cytokines. As the flow of information is
      probably multi directional, the very same cells are probably targeted for
      steroidal and peptidergic input in keeping with the existence of multiple
      autocrine and paracrine loops.

PMID- 1390294
TI  - Control of steroidogenesis in Leydig cells.
AB  - Luteinizing hormone (LH) interacts with its plasma membrane receptor to stimulate
      steroidogenesis not only via cyclic AMP but also other pathways which include
      arachidonic acid and leukotrienes and regulation of chloride and calcium
      channels. The same stimulatory pathways may lead to desensitization and down
      regulation of the LH receptor and steroidogenesis. The LH receptor exists in a
      dynamic state, being truncated, or internalized, degraded or recycled.
      Desensitization is controlled by protein kinase C (PKC) in the rat and by cyclic
      AMP dependent protein kinase and PKC in the mouse Leydig cells. Using an adapted
      anti-sense oligonucleotide strategy we have shown that the cytoplasmic C-terminal
      sequence of the LH receptor is essential for desensitization to occur. In
      contrast, these sequences of the LH receptor are not required for the stimulation
      of cyclic AMP and steroid production. We have also shown that the extracellular
      domain of the LH receptor is secreted from the Leydig cell and may act as a LH
      binding protein.

PMID- 1390295
TI  - Ontogeny and subcellular localization of 3 beta-hydroxysteroid dehydrogenase (3
      beta-HSD) in the human and rat adrenal, ovary and testis.
AB  - Primates are unique in having adrenals that secrete large amounts of the
      precursor sex steroids (PSS) dehydroepiandrosterone (DHEA) and especially DHEA
      sulfate. The adrenal PSS require the action of 3 beta-hydroxysteroid
      dehydrogenase/5-ene-4 ene isomerase (3 beta-HSD), 17 beta-hydroxysteroid
      dehydrogenase (17 beta-HSD), 5 alpha-reductase and/or aromatase to form the
      androgen dihydrotestosterone (DHT) or the estrogens 17 beta-estradiol and androst
      5-ene-diol. Knowing the crucial role of 3 beta-HSD and 17 beta-HSD in sex steroid
      biosynthesis both in classical as well as in peripheral steroidogenic tissues, we
      have concentrated our efforts on the elucidation of the molecular structure of
      these enzyme families. We have thus characterized two types of human 3 beta-HSD
      cDNA clones and their corresponding genes which encode deduced proteins of 371
      and 372 amino acids and share 93.5% homology. Human type I 3 beta-HSD is the
      almost exclusive mRNA species expressed in the placenta and skin, while human
      type II is the predominant mRNA species in the adrenals, ovaries and testes. We
      have also recently elucidated the structure of three types of rat 3 beta-HSD
      cDNAs which all encode a 372 amino acid protein. The predicted rat type I and II
      3 beta-HSD proteins expressed adrenals, gonads and adipose tissue share 94%
      homology while they share 80% similarity with the liver-specific type III 3 beta
      HSD. Transient expression of human type I and II as well as rat type I and II 3
      beta-HSD cDNAs in HeLa human cervical carcinoma cells reveals that 3 beta-ol
      dehydrogenase and 5-ene-4-ene isomerase activities reside within a single protein
      and that these cDNAs encode functional 3 beta-HSD proteins. The expressed rat
      type III protein possesses a unique property catalyzing selectively the reduction
      of 3 beta-androstane 5 alpha-steroids such as DHT. Furthermore, we have also
      demonstrated by site-directed mutagenesis that the lower activity of expressed
      rat type II compared to rat type I 3 beta-HSD protein is due to a change of four
      amino acid residues potentially involved in a membrane-spanning domain. In
      parallel, we have characterized the complete nucleotide sequence of human 17 beta
      HSD cDNA clones encoding a 327 amino acid protein as well as two in tandem 17
      beta-HSD genes. Two major 17 beta-HSD mRNA species have been detected in several
      tissues due to a tissue-specific alternative site of initiation of
      transcription.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1390296
TI  - Anabolic steroids: a review of their effects on the muscles, of their possible
      mechanisms of action and of their use in athletics.
AB  - Anabolic steroids are synthetic molecules developed in the hope of obtaining a
      complete separation of the androgenic and myotrophic (anabolic) actions of
      testosterone. Such a goal has never been fully achieved. However, some synthetic
      steroids present a partial dissociation between these two activities. Since a
      single hormonal receptor apparently mediates the androgenic as well as the
      anabolic actions of testosterone, differences in patterns of androgen
      metabolization in the muscles and the sex accessory organs have been proposed as
      a possible cause of this phenomenon. Undoubtedly, androgens are able to exert a
      trophic effect on skeletal and cardiac muscle fibres in subjects with low
      circulating levels of testosterone such as prepubertal or hypogonadal males and
      females; however, the widespread use of anabolic steroids in male athletes to
      increase their physical performances poses the question of whether these
      compounds are active in the presence of normal circulating levels of
      testosterone. Most experimental animal studies indicate that anabolic steroids
      are ineffective in this situation. Since the results of the experiments performed
      in humans are largely contradictory, it is still not clear whether anabolic
      steroids are able to improve athletic performances. These and other relevant
      issues are reviewed.

PMID- 1390297
TI  - Bridges across the "Black See" of malignant transformation!

PMID- 1390298
TI  - Towards 3-D modelling of epithelia by computer simulation.
AB  - The present work is a preliminary step towards dynamic 3-D modelling by computer
      graphics simulation of the structure of normal and pathological epithelia, using
      an expert system. In its present state, Esexsy (Epithelium Simulation by EXpert
      SYstem) allows the construction, through iterative steps, of a simple 3-D
      representation of the nasal epithelium, based on the positions, sizes and shapes
      of nuclei. The iterative process is based on statistical comparisons between
      distributions of parameter values calculated from real (2-D) histological
      sections and those issued from an equivalent computer 'section' through the
      simulated 3-D image. We show the results of attempts at simulating normal,
      metaplastic and dysplastic states of the nasal epithelium, the latter two being
      characterized by a progressive architectural disorganization, accompanied by
      nuclear size/shape alterations. The representation takes into account the size,
      shape, orientation and spatial arrangement of nuclei, with one or several layers
      from the basal lamina to the lumen. A modified Poisson point process is used at
      present to position the nuclei, which are modelled by bi-axial spheroids (from
      prolate to oblate through spherical), with random orientation and size/shape
      deviations. It should be possible to use the same computer program to simulate
      other types of epithelia and to achieve increasingly realistic representations by
      incorporating, notably, nuclear deformations and chromatin texture.

PMID- 1390299
TI  - Determination of DNA ploidy in archival tissue from non-Hodgkin's lymphoma using
      flow and image cytometry.
AB  - Paraffin-embedded tissue from a series of 40 cases of diffuse, large cell
      lymphoma was analyzed by both flow and image cytometry to compare the ability of
      these techniques to detect DNA aneuploid populations. Image cytometry (ICM) was
      performed both on nuclear suspensions and tissue sections. Twenty cases (50%)
      were non-diploid by at least one method of analysis. Twenty-five percent of the
      cases were aneuploid by flow cytometry (FCM) alone. The majority of these cases
      were near-diploid tumors which could not be resolved by ICM. Peri-tetraploid
      peaks were identified by ICM of tissue sections alone in 15% of the cases. There
      was an apparent loss of these peri-tetraploid cells during the preparation of the
      nuclear suspensions. The remaining cases showed a good correlation between all
      three methods in the determination of DNA ploidy. Flow and image cytometry are
      complimentary techniques when applied to archival tissue, however aneuploid
      populations may be missed if ICM is not performed on tissue sections.

PMID- 1390302
TI  - The treatment of high-volume testicular cancer: a persisting dilemma.

PMID- 1390300
TI  - DNA changes in progressive cervical intraepithelial neoplasia.
AB  - Cervical intra-epithelial neoplasm (CIN) is treated as a progressive lesion, even
      though most CIN will not progress to invasive cancer if left untreated. This
      study focussed on DNA-cytometric analysis of cytologic smears of patients who had
      developed invasive cancer after initial smears showing CIN. The first part of the
      study aimed at describing the DNA-cytometric changes in these progressive
      ('malignant') CIN lesions. In the second part a cluster analysis was performed on
      'malignant' CIN III lesions and CIN III lesions, with 'unknown' malignant
      potential. The results indicated that 'malignant' CIN lesions developed high DNA
      index (DI) values during malignant transformation, as demonstrated by increasing
      mean DI values, a high percentage of DNA-aneuploidy and 2.5c Exceeding Rates.
      Furthermore, a trend-like pattern of texture feature values occurred in
      'malignant' CIN lesions with increasing severity. These findings provide
      objective quantitative confirmation of the evolution of nuclear changes during
      malignant transformation. Cluster analysis showed that it was possible, using a
      set of four cytometric features, to subdivide the 'unknown' CIN III lesions into
      a cluster of lesions with feature values similar to the vast majority of the
      'malignant' CIN III lesions, and a second cluster of lesions with feature values
      dissimilar to 'malignant' CIN III. It is argued that the profile of 'malignant'
      CIN has become clearer and that the results of this study may serve as a basis
      for a more objective cytopathologic subdivision of premalignant CIN. It may be
      justified to follow up patients whose lesions do not yet fit this 'malignant'
      profile. Not treating the non-progressive lesion group will avoid putting these
      patients at risk.

PMID- 1390301
TI  - Cross resistance between radiotherapy and chemotherapy in cancer treatment: what
      can be done about it?

PMID- 1390303
TI  - Malignant bone resorption: cellular and biochemical mechanisms.

PMID- 1390304
TI  - Application of basic science to hematopoiesis and treatment of disease. 15th
      Bristol-Myers Squibb Symposium on Cancer Research held at the Fred Hutchinson
      Cancer Research Center, Seattle, November 4-5, 1991.

PMID- 1390305
TI  - Recombinant interferon alfa-2a with or without vinblastine in metastatic renal
      cell carcinoma: results of a European multi-center phase III study.
AB  - A total of 178 patients with metastatic renal cell cancer were randomized to
      receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine
      (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a
      week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks.
      The response rate was 11% for patients on monotherapy and 24% for those on
      combination treatment. The 5-year survival for 145 eligible patients was 9%,
      independently from the treatment arm. The performance status was significantly
      related to long-term prognosis, and 13% of the patients with performance status 0
      were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of
      1 and 2, respectively. The most frequent adverse events in both treatment arms
      were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances
      (68%). Leukopenia was observed more frequently with combination treatment (53%)
      than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at
      this dose and schedule has modest antitumor activity in metastatic renal cell
      cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response
      rate, but this does not translate into prolonged survival. Toxicity (except
      leukopenia) and tolerance were similar in both treatment arms.

PMID- 1390306
TI  - Effective prevention of chemotherapy--induced phlebitis by low-dose heparin: a
      prospective randomised trial.
AB  - In a prospective randomised trial patients receiving multiple-day chemotherapy
      and heparin had significantly fewer local complications at the site of venous
      access than patients who had chemotherapy alone. The need to move peripheral
      venous catheters to other sites was decreased significantly, from 36% to 6%.
      Prophylaxis of phlebitis with low-dose continuous heparin is safe, simple, cheap
      and effective. It facilitates administration of multiple-day chemotherapy for the
      patients, the nurses and the physicians.

PMID- 1390307
TI  - A comparison of CA-549 with CA 15-3 and MCA in patients with metastatic breast
      cancer.
AB  - CA 15-3, MCA, and CA-549 levels were determined in the serum of 56 patients with
      metastatic breast cancer, all of whom had visceral and/or bone metastases. CA 15
      3 was positive in the serum of 37 patients, MCA in the serum of 38 patients, and
      CA-549 in the serum of 39 patients. All 3 markers were positive in 36 patients,
      and all 3 were negative in 16 patients. In the serum of 4 patients only 1 or 2
      markers were slightly elevated. Thus, the results were identical in 52 of the 56
      patients. It is concluded that CA 15-3, MCA, and CA-549 are sensitive markers for
      advanced breast cancer, and that no advantage can be expected by combining them.

PMID- 1390309
TI  - Colorectal cancer presenting as isolated skull metastasis.

PMID- 1390308
TI  - Cisplatin-containing regimen in advanced or recurrent granulosa cell tumours of
      the ovary.
AB  - The efficacy of combination chemotherapy in advanced or recurrent disease of
      granulosa cell tumours is still not well defined. Ten patients with advanced or
      recurrent granulosa cell tumours were treated with cisplatin, adriamycin and
      cyclophosphamide (CAP). Prior to chemotherapy all patients underwent surgical
      treatment. No patient received prior hormonochemotherapy or radiotherapy. Five
      complete responses (three pathologically documented) and one partial response
      were obtained for a total response rate of 60%. One pathologically-complete
      responder relapsed after 48 months from the onset of chemotherapy, but responded
      completely to debulking surgery and radiotherapy and remains well with no
      evidence of disease 87+ months. Five patients are still alive with no evidence of
      disease at 10+, 26+, 41+, 46+, 87+ months, 1 is still alive with disease and 4
      have died at 20, 22, 28 and 60 months despite further treatment. Additional
      cooperative clinical trials are required to determine the exact efficacy of
      cisplatin chemotherapy in granulosa cell tumours.

PMID- 1390310
TI  - HIV seroprevalence among non-paediatric malignant lymphoma patients at Kenyatta
      National Hospital between March 1986 and September 1990.

PMID- 1390311
TI  - Chemotherapy of head and neck cancer.
AB  - Numerous studies have shown cisplatin-based chemotherapy to be effective in the
      treatment of head and neck cancer. Cisplatin/5-fluorouracil (5-FU) is the most
      frequently used combination regimen, but neurotoxicity, ototoxicity, and renal
      toxicity limit repeated dosing (for long-term treatment of responding patients)
      and dose intensification. In studies to date, the analogue carboplatin appears to
      have activity similar to cisplatin, the advantage of no significant
      neurotoxicity, ototoxicity, or renal toxicity, and less emetic potential. Two
      randomized trials have shown cisplatin/5-FU and carboplatin/5-FU superior in
      terms of response rate compared to single-agent therapy. Treatment with
      combinations of carboplatin/methotrexate and carboplatin/cisplatin is feasible,
      but myelosuppression is dose-limiting. As an induction regimen, carboplatin/5-FU
      yields response rates similar to cisplatin/5-FU. Overall, carboplatin has a more
      favorable toxicity profile for treating head and neck cancer patients who often
      have multiple medical problems when presenting for palliation of cancer.
      Reversible myelosuppression is dose-limiting. However, the availability of
      hematopoietic growth factors may allow investigators to safely intensify dosing,
      particularly in combined-modality curative treatment regimens for the newly
      diagnosed patient.

PMID- 1390312
TI  - High-dose progestin therapy for metastatic breast cancer.
AB  - Progestin therapy has become an established endocrine modality for the treatment
      of metastatic breast cancer, with medroxyprogesterone acetate and megestrol
      acetate being the most widely used agents. Both drugs display similar
      effectiveness as initial and secondary therapy for patients with advanced
      disease, with combined complete and partial response rates of approximately 30%
      to 40%. Uncontrolled trials have suggested that high doses of medroxyprogesterone
      may be more effective than lower doses, but randomized trials have yielded
      conflicting results. Clinical trials of megestrol acetate have demonstrated it to
      be an affective, well-tolerated oral progestin, and a recent randomized trial has
      suggested that higher megestrol acetate doses may be associated with not only
      improved response but also improved time to disease progression and survival.
      Further trials of high-dose megestrol acetate for both initial and secondary
      therapy are under way, and their results will provide valuable information
      concerning the role of such treatment.

PMID- 1390313
TI  - Use of ifosfamide in the management of breast cancer.
AB  - Ifosfamide, a cytostatic drug highly active in vivo, has slight superiority over
      cyclophosphamide. It proved effective in experimental tumor systems including the
      C3H mammary carcinoma. Clinical studies of ifosfamide as monotherapy in breast
      cancer, begun in 1974 by Ahmann et al., reported a 20% objective response.
      Subsequent trials were conducted from 1974 through 1977 using ifosfamide as
      monotherapy, and ifosfamide was also combined with other chemotherapeutic agents.
      In 1975, Hartwich and coworkers used the combination ifosfamide/vincristine with
      a 25% overall response. With the introduction of the uroprotector mesna, more
      studies were instituted. In 1984, using the IMF combination
      (ifosfamide/methotrexate/5-fluorouracil), we reported a 25% overall response.
      Other groups also reported good results for ifosfamide-containing combinations,
      with overall responses ranging from 25% to 79%. Recently, Sanchiz and Milla used
      high-dose ifosfamide to treat metastatic breast cancer, with a 40% overall
      response. In conclusion, ifosfamide's efficacy in breast cancer has been
      confirmed and the drug is highly recommended in combination chemotherapy as a
      first-line treatment.

PMID- 1390314
TI  - Carboplatin plus 5-fluorouracil and leucovorin in previously treated patients
      with metastatic breast cancer.
AB  - The commonly reported second-line chemotherapy regimens administered for
      metastatic breast cancer usually induce few responses, which last no more than 4
      to 8 months. We used carboplatin 50 mg/m2 on days 2, 3, and 4 of each course,
      leucovorin 500 mg/m2 on days 1 through 5 in 30-minute infusions, and 5
      fluorouracil (5-FU) 375 mg/m2 intravenous bolus 1 hour after each leucovorin dose
      to treat 32 patients with metastatic breast cancer. Six patients had previously
      received treatment with only one cytotoxic chemotherapy regimen, usually CMF
      (cyclophosphamide/methotrexate/5-FU). Twenty-six patients had received treatment
      with two or more regimens of chemotherapy previously, and most of them also had
      received radiotherapy and endocrine manipulations. Fifteen patients had visceral
      deposits. In cases of excessive or persistent toxicity, single daily doses were
      not reduced, but the start of the next course was delayed or its duration
      reduced. Of 26 heavily pretreated patients, 12 responded, primarily those with
      disease in lymph nodes, skin, breast, and pleura. One patient with liver deposits
      had a complete remission confirmed at laparoscopy and echogram. Survival was
      probably prolonged, with a median duration of response of 5 months (range, 3 to
      22+), and moderate side effects that did not compromise quality of life during
      treatment. The probability of response was not related to the type of
      pretreatment (with or without 5-FU) nor to response to previous treatments.

PMID- 1390315
TI  - Carboplatin alone or in combination in high-risk acute nonlymphoblastic leukemia.
AB  - The use of newly developed antileukemic agents is one of the therapeutic options
      available to overcome clinical resistance in refractory or other high-risk acute
      leukemias. Carboplatin is a second-generation platinum compound that has
      demonstrated significant activity against acute leukemia, particularly when
      administered via continuous intravenous infusion in phase I clinical trials.
      Based on the preliminary reports of these trials, we designed a phase II clinical
      trial to evaluate the efficacy and toxicity of carboplatin via continuous
      infusion (300 mg/m2/d for 5 days) for remission induction in adult patients with
      high-risk acute leukemia. Because of the significant antileukemic activity and
      the scarce extrahematologic toxicity noted in this trial, in order to increase
      the response rate, we were encouraged to try carboplatin in combination in a
      similar set of patients. A phase II study of carboplatin 300 mg/m2/d for 5 days
      in combination with etoposide 100 mg/m2/d for 3 to 4 days was designed by our
      group to treat patients with high-risk acute leukemia. This combination was
      chosen because (1) each drug has independent activity in acute nonlymphoblastic
      leukemia (ANLL) and (2) carboplatin/etoposide has been extensively tested in
      patients with small and non-small cell lung cancer, and therefore the toxicity
      and maximum tolerated dose are known. The complete remission rate achieved was
      somewhat higher (40%) than with carboplatin alone despite the increased incidence
      of extrahematologic toxicities, particularly gastrointestinal bleeding. At
      present, carboplatin should be considered as a new effective agent for the
      treatment of ANLL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390316
TI  - Neoadjuvant combination of carboplatin and 5-FU in head and neck cancer: a
      randomized study.
AB  - A prospective, randomized, multicenter study of patients with oropharyngeal and
      pharyngolaryngeal tumors compared locoregional treatment alone with neoadjuvant
      chemotherapy with carboplatin/5-fluorouracil (5-FU) followed by locoregional
      treatment. The aim of the study was to evaluate the role of chemotherapy on
      survival and on the need for mutilating surgery. Since 1988, 219 patients (105
      with oropharyngeal and 114 with pharyngolaryngeal tumors) have entered the study.
      All patients randomized to neoadjuvant chemotherapy received three cycles of
      carboplatin 400 mg/m2 day 1 and 5-FU 1 g/m2/d as a continuous infusion days 1
      through 5 every 3 weeks. Neoadjuvant chemotherapy was given to 108 patients. The
      268 evaluable courses induced a low rate of grade 3 or 4 toxicity. Four patients
      (3.6%) died of major complications. The complete response (CR) rate was 31%,
      which represented a decrease in mutilating surgery of 30%. (Patients with CRs had
      radiotherapy alone instead of radiosurgical treatment as originally planned.) The
      objective response rate was 61%. Survival curves for the chemotherapy and
      chemotherapy-naive groups were not significantly different. The rate of nodal
      recurrence was significantly higher in the chemotherapy group, however, and
      chemotherapy did not decrease the rate of second primary tumors or distant
      metastases. Thus, the justification for neoadjuvant chemotherapy may be a
      decreased rate of mutilating surgery. These preliminary results are encouraging,
      but follow-up is as yet too short to allow definite conclusions.

PMID- 1390317
TI  - Advances in the control of chemotherapy-induced emesis.
AB  - Cancer patients consistently rank nausea and vomiting as the most feared side
      effects of treatment. Cisplatin, one of the most active chemotherapeutic agents,
      causes acute emesis and a delayed emesis syndrome, which also results in
      considerable patient morbidity. Despite the use of metoclopramide-containing
      combination regimens, approximately one third of cisplatin-treated patients
      continue to experience emesis. In recent years, considerable progress has been
      made in managing chemotherapy-induced emesis. This review discusses several
      factors that have contributed to improved antiemetic control, including
      standardization of antiemetic trial methodology, insight into the pathogenesis of
      chemotherapy-induced emesis, and the development of a new class of antiemetic
      agents, the serotonin antagonists. In clinical studies performed to date, these
      agents have generally proven to be both effective and safe. Three multicenter
      trials of the selective serotonin antagonist ondansetron in the prevention of
      nausea and vomiting from cisplatin are reviewed.

PMID- 1390318
TI  - Efficacy of weekly cisplatin-based chemotherapy in recurrent and metastatic head
      and neck cancer.
AB  - After disease recurrence or dissemination, patients who had been treated
      previously with radiation with or without surgery for cancer of the head and neck
      were given either cisplatin (16 patients), cisplatin/etoposide (15 patients), or
      cisplatin/etoposide/5-fluorouracil (5-FU) (19 patients) in an ambulatory care
      clinic. Intravenous (i.v.) cisplatin 25 mg/m2 was given weekly, while etoposide
      was given i.v. (80 mg/m2) on day 1 and orally (160 mg/m2) on day 2 of every odd
      numbered week. In the three-drug regimen, 5-FU 500 mg/m2 i.v. was given every
      even-numbered week. Patients in all three groups received daily oral prednisone
      to decrease myelosuppression and oral co-trimoxazole and ketoconazole to prevent
      infection. The supportive drugs were given to all groups to keep these variables
      constant. As expected, myelosuppression did not occur in the cisplatin group,
      while the rates of severe neutropenia (less than 1.0 x 10(9)/L) in the two- and
      three-drug groups were 26% and 74%, respectively. The incidence of infection
      requiring hospitalization was low (2.5%). The response rate (complete plus
      partial) was lowest in the cisplatin group (6%) and higher in the
      cisplatin/etoposide (47%) and cisplatin/etoposide/5-FU (53%) groups. Because of
      the low response rate and the short time to progression (5 weeks) in the
      cisplatin group, 9 of these 16 patients were treated subsequently with
      cisplatin/etoposide. Time to progression and response duration were similar in
      the cisplatin/etoposide and cisplatin/etoposide/5-FU groups--12 and 14 weeks, and
      12 and 9 weeks, respectively. Median survival times of the cisplatin and
      cisplatin/etoposide/5-FU groups were 36 and 34 weeks, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390319
TI  - Cholesterol lowering and the reduction of CHD incidence and total mortality:
      results from a meta-analysis of randomized trials.
AB  - This editorial reports on a meta-analysis done on cholesterol-lowering trials.
      Coronary heart disease incidence is reported for 16 trials and total mortality
      for 19 trials. The cholesterol benefit ratio, i.e., the percent risk reduction
      divided by the percent cholesterol reduction, was analyzed in terms of total vs.
      potential modifying factors. For coronary heart disease the benefit ratio was 2.8
      (95% CL: 1.5, 4.2), and for total mortality it was 1.2 (95% CL: -0.1, 2.3).
      Cholesterol reduction had to be at least 8-9% to outweigh the negative impact of
      treatment on total mortality.

PMID- 1390320
TI  - Cholesterol biosynthesis and metabolism.
AB  - Cholesterol plays an essential role in cell membrane synthesis and in cell growth
      and differentiation. In mammalian cells, cholesterol can be synthesized from
      acetate precursors or taken up from dietary or exogenous sources. The major
      catabolic route for disposal of cholesterol involves conversion into excretable
      bile acids. The maintenance of cholesterol homeostasis is influenced and
      carefully controlled by multiple feedback mechanisms. The key regulatory targets
      of these feedback mechanisms are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase in cholesterol biosynthesis, the low-density lipoprotein (LDL) receptor
      in cholesterol uptake, and cholesterol 7 alpha-hydroxylase in cholesterol
      catabolism. The elucidation of regulatory mechanisms in cholesterol metabolism
      has been greatly facilitated by the discovery of a new class of lipid-lowering
      drugs, the HMG-CoA reductase inhibitors. In addition to proving therapeutically
      useful in the treatment of hypercholesterolemia, these drugs have revealed novel
      regulatory steps in cholesterol metabolism and several new targets for future
      drug development. This manuscript reviews recent developments in the cholesterol
      biosynthetic pathway and the regulatory mechanisms that maintain cholesterol
      homeostasis.

PMID- 1390322
TI  - Can we really justify the treatment of silent ischemia in 1992? No!
AB  - Since the advent of ambulatory ST-segment monitoring, it has been established
      that silent ischemia is common in patients with various coronary artery disease
      syndromes, and such silent episodes represent up to 80% of all ischemic episodes.
      It appears to be associated with an adverse prognosis when compared with
      similarly characterized patients without silent ischemia during daily life.
      Silent ischemia does not, however, bother the patients, by virtue of the fact
      that it is silent, and therefore treatment of such ischemia must be justified by
      an improved outlook for the patient, rather than symptom relief. There is no
      direct evidence to date that silent ischemia is associated with acute myocardial
      infarction or sudden cardiac death in a cause-and-effect relationship, or that
      reduction or eradication of silent ischemia will lead to an improved prognosis
      for the patient; indeed, we have been unable to demonstrate any significant
      improvement in outlook when using the various antianginal/antiischemic agents at
      our disposal. Until we can demonstrate a benefit to the patient by detecting and
      treating silent ischemia, we should not waste large resources attempting to
      eradicate something whose significance we do not understand.

PMID- 1390324
TI  - Do calcium entry blockers act on circulating ionized calcium?

PMID- 1390323
TI  - Cholesterol and coronary disease--outstanding questions.
AB  - The role of raised blood cholesterol in causing coronary atheroma is established,
      and a high dietary intake of saturated fat is a leading cause of coronary
      disease. Reduction of hypercholesterolemia in middle-aged males reduces CHD
      incidence, mostly nonfatal myocardial infarction. But there are many unresolved
      questions that should lead to a selective and moderate approach to the management
      of hypercholesterolemia. These include lack of the exact knowledge of how raised
      cholesterol leads to atheroma, equivocal evidence of whether reduction of
      hypercholesterolemia causes regression of atheroma, uncertainty about how far
      down cholesterol levels can safely be reduced and whether the cost-benefit always
      justifies action, the fact that reduction of hypercholesterolemia does not reduce
      total mortality and may increase noncardiac mortality, and insufficient evidence
      as to whether the same policies should be adopted for women, the elderly, and
      adolescents as for middle-aged men.

PMID- 1390321
TI  - Advances in thrombolytic therapy.
AB  - Alteplase and saruplase are more fibrin-specific thrombolytic drugs than
      anistreplase. These and the thrombolytic drugs of the first generation
      (streptokinase and urokinase) have shortcomings and limitations. The prolonged
      intravenous maintenance infusions have been replaced by a bolus injection,
      accelerated infusions, or the combined intravenous administration of thrombolytic
      agents. Numerous truncated alteplase or saruplase molecules have been constructed
      by deletion and domain substitution or hybrids made of the two molecules without
      gaining in thrombolytic potency. Recombinant staphylokinase and plasminogen
      activator from bat saliva have some interesting properties and are being
      investigated. Thrombus-targeted thrombolytic drugs were constructed using
      monoclonal antibodies against fibrin fragments or against epitopes of activated
      platelets. Fibrin-specific thrombolytic drugs require the concomitant use of a
      potent antithrombotic drug to prevent reocclusion. Whether hirudin or synthetic
      thrombin inhibitors are superior to heparin and whether novel antiplatelet
      agents, including monoclonal antibodies to platelet receptors and disintegrins,
      are more effective than aspirin is under clinical investigation. The place of
      stable analogues of prostacyclin during thrombolytic treatment is still
      unsettled.

PMID- 1390325
TI  - Syncope and recurrent long sinus arrest in vasospastic angina.

PMID- 1390326
TI  - Antihypertensive efficacy and effects of nitrendipine on cardiac and renal
      hemodynamics in mild to moderate hypertensive patients: randomized controlled
      trial versus hydrochlorothiazide.
AB  - In this study antihypertensive efficacy, safety, and the effects of short-term
      nitrendipine administration on central and renal hemodynamics were evaluated in
      mild to moderate hypertensives. Our final goal was to ascertain whether the
      reduction in blood pressure induced by nitrendipine treatment was associated with
      maintained renal function. After a run-in period with placebo, 26 hypertensives
      without cardiac or renal disease were randomly assigned to a double-blind 8-week
      controlled trial with nitrendipine (N) 20 mg once a day (13 pts) or
      hydrochlorothiazide (HCT) 25 mg once a day (13 pts). Renal hemodynamic
      measurements included effective renal plasma flow (ERPF) and glomerular
      filtration rate (GFR) by radionuclide study using I-131 hippuran and Tc-99m,
      according to the methods described by Schlegel and Gates, respectively. Effective
      renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF), and
      renal vascular resistance (RVR = MBP x 80/ERBF) were also calculated. Other
      hemodynamic measurements included cardiac index (CI), left ventricular (LV)
      ejection fraction (EF), and total peripheral resistance (TPR) measured by the
      first-pass radionuclide angiography technique. At the end of N or HCT
      administration significant decreases (p less than 0.001) in SBP, DBP, and MBP vs.
      baseline values were observed in both hypertensive groups. In the N group a
      significant decrease (p less than 0.01) in TPR and RVR, and significant increases
      (p less than 0.05) in CI, ERPF, and ERBF were observed. In the HCT group a
      significant decrease (p less than 0.05) in RVR was found without significant
      changes in other hemodynamic parameters. No important side effects were observed
      with either therapy. In conclusion, nitrendipine was effective in reducting blood
      pressure in mild to moderate hypertensive patients and exerted favorable effects
      on cardiac and renal function.

PMID- 1390327
TI  - Regression of left ventricular hypertrophy in "previously untreated" hypertensive
      blacks after 6 months of blood pressure reduction with alpha- and beta-adrenergic
      blockade and thiazide therapy.
AB  - In 10 hypertensive black patients who were "previously untreated" (defined as no
      antihypertensive therapy for a minimum of 12 months prior to enrollment) and who
      had LVH (defined by an increase in both wall thickness and echocardiographically
      determined LV mass), we studied the effects of treatment with either labetalol,
      an alpha- and beta-adrenergic blocker (three patients), or labetalol plus
      hydrochlorothiazide (seven patients). After 6 months of effective
      antihypertensive therapy, there was a 12% decrease in LV mass for the entire
      group. However, the extent of LVH regression was highly variable among individual
      patients.

PMID- 1390328
TI  - Low-dose verapamil in middle-aged and elderly patients with angina pectoris: no
      evidence of increased susceptibility to the cardiac effects.
AB  - This study investigated the cardiac responses and pharmacokinetics following the
      acute and chronic administration of verapamil in 14 middle-aged and elderly
      patients with ischemic heart disease (age range 42-76 years). There were small
      significant reductions in heart rate during chronic treatment, but there were no
      significant effects on the PR intervals following either single intravenous
      administration or after 4 weeks continued treatment. Left ventricular ejection
      fractions at rest or exercise were not significantly changed following either
      acute intravenous (rest 33%; exercise 38%) or chronic oral dosing with verapamil
      (rest 35%; exercise 43%) when compared with placebo (rest 34%; exercise 42%).
      There were no independent age-related effects on these indices of cardiac
      function, nor on apparent liver blood flow, nor on blood pressure and heart rate.
      The plasma clearance of verapamil was reduced from 1.3 l/min after acute dosing
      to 0.8 l/min during chronic treatment, but there was no significant independent
      age-related effect. The results of this study suggest that middle-aged and
      elderly patients with ischemic heart disease do not show enhanced cardiovascular
      responses to low doses (5 mg intravenously and 80 mg tid orally) of the calcium
      antagonist drug, verapamil.

PMID- 1390329
TI  - Reduction of exercise-induced regional contractile dysfunction in dogs using a
      novel calcium channel blocker (Ro 40-5967).
AB  - Ro 40-5967 is a calcium channel blocker with a novel chemical structure. The
      purpose of this study was to evaluate the effects of Ro 40-5967 on systemic
      hemodynamics and regional contractile function in a canine model of chronic
      coronary artery stenosis in which no contractile dysfunction is observed at rest,
      but dynamic exercise elicits regional myocardial ischemia and contractile
      dysfunction. Thirteen dogs were chronically instrumented with sonomicrometers for
      the measurement of wall thickness in the anterior and posterior left ventricular
      walls, a micromanometer for measuring left ventricular pressure (LVP) and its
      first derivative (dP/dt), and a catheter in the aorta for measuring systemic
      arterial pressure. An ameroid constrictor on the left circumflex coronary artery
      produced gradual constriction of the vessel such that treadmill exercise elicited
      regional contractile dysfunction. Runs were repeated 3 hours later after the
      administration of Ro 40-5967 (0.3 mg/kg, IV). During the control run, regional
      systolic wall thickening in the posterior wall fell from 25.5 +/- 6.3% (SD) to
      15.9 +/- 5.1% (p less than 0.05). Ro 40-5967 did not change resting function in
      the poststenotic myocardium (26.9 +/- 8.4%) but improved regional function during
      the run to 18.2 +/- 6.2% (p less than 0.05). This improvement was associated with
      a slight decrease in the exercise heart rate (213 +/- 18 vs. 200 +/- 16 bpm, NS),
      no change in peak ventricular pressure (156 +/- 22 vs. 157 +/- 20 mmHg), mean
      aortic pressure (123 +/- 19 vs. 118 +/- 20 mmHg), dP/dt (5129 +/- 1143 vs. 5288
      +/- 1120 mm Hg/sec), or systolic wall thickening in a distant control
      region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390331
TI  - Choice of ACE inhibitor for congestive heart failure.

PMID- 1390330
TI  - Comparison of captopril with enalapril in the treatment of heart failure:
      influence on hemodynamics and measures of renal function.
AB  - Twenty-nine patients with severe heart failure (NYHA III) were randomly assigned
      to receive therapy with an angiotensin converting enzyme inhibitor (ACE
      inhibitor), either captopril or enalapril. The mean daily dosage of captopril was
      56 +/- 5 mg and of enalapril 9.5 +/- 0.4 mg. After a mean of 8 +/- 1 days, the
      influence of both ACE inhibitors on hemodynamics and renal function was compared.
      The mean arterial pressure in the group treated with captopril (Group A) fell by
      9 +/- 3 mmHg (p less than 0.01), and in the group treated with enalapril (Group
      B) it fell by 12 +/- 3 mmHg (p less than 0.001). The difference between the
      groups was not significant. Heart rate decreased in both groups; however, the
      change was significant (p less than 0.05) only in patients treated with enalapril
      (-11 +/- 3 bpm in Group B vs. -7 +/- 4 bpm in Group A). Stroke volume index
      increased by 6 +/- 3 ml/m2 in Group A (p less than 0.05) vs. 10 +/- 2 ml/m2 in
      Group B (p less than 0.01). The increase in stroke volume index was not
      significantly different between the two groups. Mean decreases in pulmonary
      artery and right atrial pressure were also comparable in both groups. Thus,
      hemodynamic improvements were similar during therapy with either captopril or
      enalapril. Serum sodium and potassium before therapy were 137 +/- 1 mmol/l and
      4.1 +/- 0.1 mmol/l, respectively, in group A and 139 +/- 1 mmol/l and 4.0 +/- 0.1
      mmol/l, respectively, in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390332
TI  - Long-term hemodynamic effects of nifedipine on congenital heart disease with
      Eisenmenger's mechanism in children.
AB  - The hemodynamic effect of long-term nifedipine medication was studied in 10
      children, 3-12 years of age, five with ventricular septal defect and five with
      complete atrioventricular septal defect; all had Eisenmenger's reaction, seven
      also had Down's syndrome. They underwent heart catheterization prior to and
      during 1-4 years of nifedipine therapy. Fick's principle was used to calculate
      the ratio of pulmonary arterial pressure to aortic pressure (PAP/PAO), the ratio
      of pulmonary flow to aortic flow (QP/QS), as well as the ratio of pulmonary
      vascular resistance to aortic vascular resistance (RP/RS). In the seven children
      under 8.8 years, nifedipine caused a significant drop in PAP/PAO (p less than
      0.004), a slight increase in arterial O2 saturation, a significant increase in
      QP/QS (p less than 0.02), and a decrease in RP/RS (p less than 0.02). The
      nifedipine effect was age related. On nifedipine, breathing oxygen resulted in,
      independent of age, a significant increase in QP/QS (p less than 0.003) and a
      significant decrease in PAP/PAO (p less than 0.04) and in RP/RS (p less than
      0.003). Direct O2 consumption measurements before and during oxygen breathing in
      six patients demonstrated no significant change in RP, RS, QP, or QS indices.
      Nifedipine had a relaxing effect on the pulmonary vascular bed, especially in the
      younger child with Eisenmenger's mechanism. On nifedipine therapy, O2 produced a
      more complex hemodynamic reaction that was not restricted to the pulmonary
      circulation alone.

PMID- 1390333
TI  - Evaluation of bepridil efficacy by electrophysiologic testing in patients with
      recurrent ventricular tachycardia: comparison of two regimens.
AB  - The purpose of the study was to evaluate this effect of different doses of
      intravenous and oral bepridil on the induction of ventricular tachycardia. Thirty
      eight patients underwent electrophysiologic evaluation for recurrent ventricular
      tachycardia (VT). Sustained monomorphic VT was induced by programmed ventricular
      stimulation, using up to three extrastimuli in all patients. The effects of
      intravenous bepridil (2 mg/kg) were evaluated during the initial study.
      Intravenous bepridil prevented the induction of sustained VT in eight patients
      (21%). Electrophysiologic study was repeated after oral bepridil. In six patients
      the study was stopped because of adverse effects or VT recurrence. Thirty-two
      patients underwent repeat study 7 days later, taking oral bepridil, 500 mg/day (n
      = 16) or 900/day (n = 16). A dose of 500 mg/day of bepridil prevented the
      induction of sustained VT in only one patient. A dose of 900 mg/day of bepridil
      prevented the induction of sustained VT in eight patients. There were no
      significant clinical adverse effects, except in one patient receiving intravenous
      bepridil. The response to intravenous bepridil did not predict the response to
      oral bepridil. The response to intravenous or oral bepridil was not related to
      the plasma level of bepridil but was related to a higher left ventricular
      ejection fraction. Eight patients (21%) in whom VTs were noninducible on oral
      bepridil were discharged on 300 mg/day of bepridil if their initial loading dose
      was 500 mg/day or on 600 mg/day if their initial loading dose was 900 mg/day.
      They remained free of VT during a follow-up of at least 6 months.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390334
TI  - Epithelial-specific gene expression during differentiation of stratified primary
      human keratinocyte cultures.
AB  - Cultured epithelial cells are used to generate extensive patches of autologous
      skin equivalent for patients with burns or wounds and to investigate the growth
      and differentiation of epithelia in vitro. We have undertaken a comprehensive
      study of the morphological and molecular events that occur during culturing of
      human foreskin keratinocytes at the liquid-air interface on a dermal equivalent
      consisting of a collagen matrix containing fibroblasts. Using radioactively
      labeled RNA probes for mRNAs and monoclonal antibodies for proteins, we found
      that the expression of a comprehensive set of differentiation stage-specific
      genes was affected by the type of fibroblasts included in the matrix as well as
      by the age of the culture. The expression of these genes was not always
      coordinated and could not be predicted from the histological appearance of the
      stratified epithelium. Surprisingly, the mouse fibroblasts promoted epithelial
      differentiation much more closely resembling foreskin than did the homologous
      primary foreskin fibroblasts.

PMID- 1390335
TI  - 12-O-tetradecanoylphorbol-13-acetate induces transient cell cycle arrest in G1
      and G2 in metastatic melanoma cells: inhibition of phosphorylation of p34cdc2.
AB  - The growth of Demel human metastatic melanoma cells was inhibited by 12-O
      tetradecanoylphorbol-13-acetate (TPA) and other nonphorbol tumor promoters
      including palytoxin and okadaic acid. Using flow cytometry, we have demonstrated
      that the cells arrested growth in G1 and G2 phases of the cell cycle. Detailed
      analysis of the kinetics of the growth arrest in unsynchronized cells showed that
      (a) the growth arrest was transient and peaked 16-20 h following addition of TPA;
      (b) effects of TPA on cell growth began within 1-2 h after the addition; and (c)
      cells completed S phase and arrested in G2. In addition, TPA induced a pronounced
      morphological change, which peaked by 1 h and gradually subsided over 24 h. In
      populations of cells synchronized in G1 using lovastatin, (a) addition of TPA
      blocked the onset of DNA synthesis up to the end of G1; (b) the lag between
      addition of the drug and onset of DNA synthesis was less than 30 min; and (c)
      addition of TPA at the end of G1 prevented the increased phosphorylation of
      p34cdc2, as determined by immunoprecipitation. The experiments reported here show
      that TPA transiently blocked the proliferation of Demel melanoma cells at the G1
      S border and in G2, thus preventing cells from progressing through the cell
      cycle. These experiments suggest that pathways involving protein kinase C
      interact with and rapidly alter the molecular pathways involving p34cdc2 which
      regulate the onset of DNA synthesis and the G2-M transition.

PMID- 1390336
TI  - Identification and characterization of the regulated pattern of expression of a
      novel mouse gene, meg1, during the meiotic cell cycle.
AB  - The gene designated meg1 (meiosis expressed gene) is a new mouse gene identified
      during a search for mammalian genes potentially involved in meiotic processes.
      Two classes of complementary DNAs were isolated from an adult mouse testis
      complementary DNA library, which shared the same 3' end including the entire
      putative coding region but differed in their 5' ends. Only one of these
      complementary DNA classes appeared to correspond to the very abundant 0.75
      kilobase testicular transcript of meg1. Sequence analysis predicts a 10.8
      kilodalton protein which is highly charged and lysine rich. It is also relatively
      rich in potential phosphoacceptor amino acids (approximately 17%), several of
      which are located in phosphorylation consensus sequences. The pattern of
      expression of meg1 was studied utilizing a combined Northern blot and in situ
      hybridization analysis. Of the adult tissues examined, meg1 transcripts were
      detected exclusively in testis. Analysis of mRNA from testes of two germ cell
      deficient mutant strains did not reveal significant levels of meg1 transcripts.
      Analysis of RNA from enriched populations of spermatogenic cells from adult
      testes and localization by in situ hybridization revealed that meg1 transcripts
      are most abundant in pachytene spermatocytes. These results suggest a role for
      meg1 during germ cell differentiation, possibly during meiotic prophase.

PMID- 1390337
TI  - Complementary DNA cloning of a novel epithelial cell marker protein, HME1, that
      may be down-regulated in neoplastic mammary cells.
AB  - A full-length complementary DNA clone from a normal human mammary epithelial cell
      (strain 184) encoding a 25-kilodalton protein, HME1, was isolated. Expression of
      HME1 RNA appears to be limited to epithelial cells. The HME1 sequence has
      extensive sequence homology with bovine 14-3-3 protein, which is an activator of
      tyrosine and tryptophan hydroxylase. However, the tissue distribution,
      arrangement of charged amino acids, and location of potential phosphorylation
      sites of HME1 differ from those of 14-3-3. Compared with normal mammary
      epithelial cells, expression of HME1 RNA was dramatically low in two cell lines
      derived from human mammary carcinoma that were examined, and in a line of normal
      mammary epithelial cells transformed by oncogenes. HME1 therefore appears to be a
      cellular differentiation marker that may be down-regulated during neoplastic
      transformation.

PMID- 1390338
TI  - Functional dissection of AP-1 transcription factors using the Gal4 adaptor assay.
AB  - In the Gal4 adaptor assay, leucine zipper-containing proteins are tethered
      indirectly to the promoters of Gal4-responsive reporter genes via synthetic
      protein chimeras consisting of a Gal4 DNA-binding domain with an attached leucine
      zipper. Ternary complexes composed of the DNA binding site, the adaptor protein,
      and a leucine zipper factor can stimulate reporter gene activity, provided that
      the latter component possesses a transcriptional activation domain. This system
      is used to assay the transcriptional function and the interactions between
      various AP-1 factors.

PMID- 1390339
TI  - Identification of a human chromosome 11 gene which is differentially regulated in
      tumorigenic and nontumorigenic somatic cell hybrids of HeLa cells.
AB  - The tumorigenicity of HeLa cells in nude mice can be suppressed by the addition
      of a normal human chromosome 11 in somatic cell hybrids. We have attempted to
      identify specific genes involved in this phenomenon by transfecting a
      complementary DNA expression library into a tumorigenic HeLa-fibroblast hybrid. A
      cell line designated F2 was isolated which displayed morphological features of
      the nontumorigenic hybrids, demonstrated reduced tumorigenicity in nude mice, and
      showed an 85% reduction in alkaline phosphatase, a consistent marker of the
      tumorigenic phenotype in these cells. F2 contained a single exogenous
      complementary DNA, which was recovered by polymerase chain reaction and
      designated HTS1 because of its potential association with "HeLa tumor
      suppression." Northern blot studies suggested differential regulation of the HTS1
      gene dependent on the tumorigenicity of the cell. In nontumorigenic hybrids, RNA
      species of 2.8, 3.1, and 4.6 kilobases were identified. In two tumorigenic hybrid
      lines, the 2.8-kilobase species was markedly reduced or absent. Similarly, three
      nontumorigenic human keratinocyte lines expressed all three RNA species, whereas
      several tumorigenic cervical carcinoma cell lines lacked the 2.8-kilobase
      species. Chromosome localization studies mapped the HTS1 gene to chromosome
      11p15, a region of chromosome 11 that is believed to contain a tumor suppressor
      gene. These findings indicate that HTS1 represents a novel chromosome 11 gene
      which may be a target of the tumor suppressor gene active in this system.

PMID- 1390341
TI  - Multiple fractions in the treatment of head and neck cancer.
AB  - Fifty-eight cases of head and neck cancer received hyperfractionated accelerated
      radiotherapy, with treatment three times daily to 47.5-54 Gy over 12-20 days. A
      total of 69% had a complete response within 3 months, and the actuarial survival
      was 52% at 1 year, 41% at 2 years, 43% at 3 years and 38% at 4 years. Acute
      reactions were rather more pronounced (31%) and late necrosis (15%) was more than
      would be expected with conventional fractionation. It is suggested that multiple
      fractions carried out by a small centre, are feasible and will reduce hospital
      stay.

PMID- 1390340
TI  - Efficacy of twice daily versus three times daily oral ondansetron in the
      prevention of chemotherapy induced emesis: a randomized, single-blind,
      multicentre study. The Ondansetron International Emesis Study Group.
AB  - Following a single intravenous dose given pre-chemotherapy, the efficacy and
      tolerability of oral ondansetron treatment given twice daily was compared with
      the established three times daily oral supplementary regimen in the prophylaxis
      of nausea and vomiting induced by cyclophosphamide (greater than or equal to 500
      mg/m2) in combination with doxorubicin (greater than or equal to 40 mg/m2) or
      epirubicin (greater than or equal to 40 mg/m2). Oral ondansetron given twice
      daily or three times daily was equally effective in controlling nausea and
      emesis. The twice daily oral treatment prevented emesis in 73% of patients in the
      first 24 hours and in 65% of patients over 3 days. Both dose schedules were safe
      and were tolerated well. Twice daily oral ondansetron showed good efficacy for
      controlling emesis and nausea in oncology outpatients.

PMID- 1390342
TI  - Stage I seminoma of the testis: is post-orchidectomy surveillance a safe
      alternative to routine postoperative radiotherapy?
AB  - Experience with the management of 128 patients with Stage I testicular seminoma
      over a 10-year period, 1980-1989, is presented. Fifty-six patients were treated
      with post-orchidectomy radiation therapy and 72 patients were put on
      surveillance. Patients thought to be at higher risk of relapse were generally
      treated with radiotherapy. There have been no tumour related deaths in this
      series; 5.4% of the irradiated group and 18% of patients on surveillance have
      relapsed to date. All relapses have been salvaged with further therapy and are
      currently in complete remission. In this interim analysis, surveillance appears
      to be a safe alternative to adjuvant radiation therapy provided regular,
      prolonged follow-up can be ensured. Surveillance is, however, time consuming and
      resource demanding, and should be undertaken only as part of a formal clinical
      study. Adjuvant post-orchidectomy radiotherapy should be considered the treatment
      of choice until further long-term data are available.

PMID- 1390343
TI  - Radiotherapy for the treatment of recurrent craniopharyngioma.
AB  - Twenty-five patients with craniopharyngioma received radiotherapy at the time of
      recurrence. The 10-year progression free survival and survival from the time of
      recurrence were 72% and 77% respectively. Nineteen patients underwent surgery
      prior to radiotherapy (6 partial excision, 4 decompression and 9 cyst
      aspiration). The extent of resection at the time of recurrence did not influence
      the outcome. Apart from pituitary failure there was no serious morbidity
      associated with this approach. The results of radiotherapy at recurrence are
      similar to those of conservative surgery and radiotherapy at the time of
      presentation. It suggests that radiotherapy remains an effective treatment
      modality at the time of recurrence of craniopharyngioma and it may therefore be
      delayed in situations where immediate radiation is not advisable. However, the
      high recurrence rate in incompletely excised craniopharyngioma, together with the
      potential risk of additional morbidity and mortality from undiagnosed progressive
      tumour and salvage surgery, would argue for a policy of radiotherapy as part of
      the initial treatment of incompletely excised craniopharyngioma.

PMID- 1390344
TI  - Value of conformal planning in the radiotherapy of soft tissue sarcoma.
AB  - The late complications and subsequent limb function seen following treatment of
      extremity sarcoma are related to the radiation dose used and the volume of tissue
      irradiated. The potential value of the use of 3D-planning and conformal blocking
      has been studied in 11 patients with lower limb sarcoma. Tumour, target and
      normal tissue volumes were reconstructed in 3D following a CT planning scan. Dose
      calculations were performed for conventional and conformal plans, using
      customized blocks with a margin of 6 mm around the target volume. No compromise
      of target dosimetry was permitted. The volumes of tissue receiving 50%, 80% and
      90% of the prescribed dose were compared using cumulative volume dose histograms.
      The treatment volume was reduced in all patients, and by greater than 20% in four
      of five with thigh tumours. The mean volume of muscle outside the target volume
      which was irradiated to the 50% isodose was 4.2 litres. The volume irradiated to
      90% or greater isodose was reduced by greater than 30% in five of eight patients
      with thigh and lower leg tumours. Similarly, the volumes of femur, tibia/fibula
      and ilium were reduced by 38%, 18% and 14% respectively by conformal blocking.
      Considerable sparing was achieved in the volumes of pelvic contents irradiated,
      including gonads and rectum. This simple, but time consuming, technique can
      achieve major reductions in normal tissue irradiation with potential improvements
      in limb function. To confirm its value and safety, prospective randomized trials
      must be performed and similar advances in patient immobilization and treatment
      verification are essential.

PMID- 1390345
TI  - A comparison of manual and remote afterloading in the treatment of carcinoma of
      the cervix: increasing dose rate with a flexible applicator.
AB  - A historical cohort design was used to assess the effect of introducing a remote
      afterloading system with a flexible applicator for the intracavitary treatment of
      cervical cancer. One hundred and sixty-eight patients treated for the 5 years
      prior to its introduction were compared to 84 patients treated for the first 3
      years of its use. Patients were comparable with respect to age and stage.
      Treatment policies and techniques remained the same during the study period.
      Average dose rate to point A increased from 0.46 Gy/hr to 0.67 Gy/hr. The 3-year
      actuarial survival was equivalent between the two treatment modalities: 67.7%
      (manual), and 60.6% (remote). Patterns of local recurrence and distant failure
      were also equivalent between the two groups. Severe complication rates were
      comparable (8.3% manual, 6.3% remote) despite the increase in dose rate,
      confirming that the remote afterloading system can be safely adapted to a
      flexible applicator. The introduction of the remote afterloading system resulted
      in a 72% reduction in radiation exposure to staff.

PMID- 1390346
TI  - Provision of cancer treatment services: the role of a district general hospital
      department of clinical oncology.
AB  - Recent reports from the Royal College of Radiologists have highlighted the debate
      surrounding the provision of cancer services. This review describes the work of a
      district hospital based department of clinical oncology, emphasizing the access
      to and the outcome and scope of treatment. The findings indicate that district
      general hospital based cancer centres can provide a comprehensive, accessible,
      high quality consultant based service.

PMID- 1390347
TI  - Radiation therapy: a long term cost benefit analysis in a North American region.
AB  - The annual cost for a concentrated, high volume radiation therapy (RT) department
      during 1977 was 3.79 million Canadian dollars (C$). From a population of 1.14
      million, 955 patients were treated with RT during 1977 at an average cost of
      C$3969 per patient. It is estimated that 225 will survive 15 years at a cost of
      C$1123 per survivor-year. The area under the RT survival curve presented
      indicates that RT given in 1977 will contribute to 5730 person-years of life at a
      cost of C$661 per person-year or C$1.82 per person-day (little more than the cost
      of a city bus ride). The cost to the community is C$3.32 per head per year. A 6
      MV workhorse linear accelerator and its vault will contribute to one person-year
      of life at a cost of C$35.04 (or C$0.68 per person-week). RT is cheaper than
      various listed medical and surgical procedures in terms of cost per procedure or
      cost per year of life gained. All costs are adjusted to the 1988 C$.

PMID- 1390348
TI  - Decision analysis in oncology: panacea or chimera?
AB  - A review of the literature on the use of decision analysis in clinical oncology
      shows that, although these techniques have been available for more than 25 years,
      they have not been widely applied: only 19 decision analyses of therapeutic
      management in clinical oncology were found. The main disadvantages concern the
      difficulty of accurately assessing probabilities and defining measures of
      outcome. Time-consuming analysis may produce results that are either equivocal or
      simply confirm the expectations of common sense. If the basic design fails to
      include all relevant factors then any conclusions will be of little value. The
      main advantages are that, by demanding that problems be explicitly stated and
      analysed in a logical fashion, deficiencies in current knowledge, belief and
      practice are identified. The usefulness of these techniques lies in formulating
      management guidelines, either for treatment or for follow-up. They have only a
      limited role in decision making for individual patients.

PMID- 1390349
TI  - Soft tissue sarcomas.

PMID- 1390350
TI  - Carboplatin and retroperitoneal fibrosis.
AB  - A patient treated for ovarian epithelial cancer by total abdominal hysterectomy
      (TAH), bilateral salpingo-oophorectomy (BSO), total omentectomy and five courses
      of single agent carboplatin chemotherapy, developed retroperitoneal fibrosis.
      This was diagnosed at exploratory laparotomy 6 months after completing treatment.
      No predisposing drug history existed in this patient. We believe that there have
      been no previous reports of an association between retro peritoneal fibrosis and
      carboplatin treatment.

PMID- 1390351
TI  - Neurotoxic treatment in a patient with brachial neuritis associated with
      Hodgkin's disease.
AB  - Brachial neuritis is a rare form of neuropathy associated with Hodgkin's disease.
      In the patient we describe, a brachial neuritis occurred during chemotherapy for
      Hodgkin's disease. He later developed a marked sensory peripheral neuropathy with
      vincristine. Lhermitte's sign also developed following modest doses of
      radiotherapy (35 Gy in 20 fractions to the whole cervical cord). We suggest that
      neurotoxic treatment must be given with extra care to patients with non
      metastatic tumour induced neuropathies.

PMID- 1390352
TI  - Enhanced normal tissue response to radiation in a patient with discoid lupus
      erythematosus.
AB  - We report the case of a patient with discoid lupus erythematosus who developed a
      severe skin reaction whilst undergoing mantle irradiation for non-Hodgkin's
      lymphoma. Widespread moist desquamation occurred after a skin dose of only 17 Gy
      and was associated with an abscopal response outside the treatment area. The case
      illustrates the need for extreme caution when administering radiotherapy to
      patients with discoid or systemic lupus erythematosus.

PMID- 1390353
TI  - Idiopathic epidural lipomatosis as a cause of pain and neurological symptoms
      attributed initially to radiation damage.
AB  - Epidural lipomatosis is a rare condition in which overgrowth of extradural fat
      can lead to back pain, spinal cord compression and radiculopathy. A 51-year-old
      man developed back pain and reduced mobility following a standard course of
      radiotherapy for a Stage I seminoma. His symptoms and radiological appearances
      were initially attributed to radiation fibrosis. Further investigations and
      operative intervention revealed epidural lipomatosis. The excess lipomatous
      tissue was removed with complete resolution of his symptoms.

PMID- 1390354
TI  - Hyperfractionated accelerated radiotherapy for carcinoma of the oesophagus.

PMID- 1390355
TI  - The concept of sign in the work of Vygotsky, Winnicott and Bakhtin: further
      integration of object relations theory and activity theory.
AB  - In a recent paper Ryle introduced the idea of integrating object relations theory
      and activity theory, a conceptual tradition originated by Vygotsky and developed
      by a number of Soviet psychologists during the previous decades. A specific
      aspect of this integrative perspective will be examined, implied in Ryle's paper
      but not elaborated by him. It is the issue of sign mediation which was Vygotsky's
      primary contribution to the methodological problems of modern psychology. The aim
      is to show that object relations theory, especially the work of Winnicott, may
      bring fresh understanding into Vygotsky's early notions. It is further claimed
      that, by introducing the contribution of Mikhail Bakhtin and his circle to the
      notion of sign mediation, the profundity in Winnicott's understanding of the
      transitional object and of the potential space may be more fully appreciated. At
      the same time the ideas of Winnicott and Bakhtin will jointly clarify the
      limitations in Vygotsky's sign conception.

PMID- 1390356
TI  - Mysticism and psychosis: the fate of Ben Zoma.
AB  - This paper examines the link between psychosis and mystical study through the
      cases of four young men who 'entered the garden' of Jewish mystical speculation
      and subsequently became psychotic. The role of such study as a precipitating
      factor is suggested, as three had no signs of disturbance prior to their mystical
      studies. All had suffered personal losses, and their choice of mystical texts and
      rites showed that their attraction to mysticism included a search for atonement
      for guilt they felt over their loss. The features of normative mysticism are
      presented with each case and it is apparent that hallucinations, grandiose and
      paranoid delusions, and social withdrawal, are phenomena that do not distinguish
      the psychotic from the mystic. Diagnosis of psychosis is made on the basis of
      duration of the state, ability to control entry into the state and the associated
      deterioration of habits, particularly the neglect of daily religious duties.
      These findings emphasize the need for the examining psychiatrist to be aware of
      the cultural background, despite the presence of seemingly florid
      psychopathology. Four eminent Rabbis entered the garden of mystical speculation.
      Ben Azzai glimpsed and died. Ben Zoma glimpsed and was damaged (lost his sanity).
      Elisha ben Avuyah lost his faith. Rabbi Akiva departed in peace.

PMID- 1390357
TI  - Human motivation objectively, experimentally analysed.
AB  - The growth of validated objective devices, and of knowledge of ergic and
      sentiment structure has now, for 20 years, put new instruments (MAT and SMAT) in
      the hands of psychological practitioners. They have been slow to recognize,
      however, the theoretical powers in conflict measurement, decision theory, the
      general dynamic calculus, and structured learning theory which this has brought
      about. Illustration is given here of the experimental and clinical gains, with a
      view to the growth of several areas inaccessible to bivariate experiment.

PMID- 1390358
TI  - Could 'objective, experimental' analysis of human motivation really improve
      psychotherapy?
AB  - Cattell is a founding father of modern, multivariate psychological method and his
      paper is a fine introduction to his views on motivation which have perhaps
      received less attention in Britain than they deserve. However, it was the
      unanimous opinion of three referees that it needed to be followed by a dissenting
      voice. In this counterargument I suggest that Cattell's presentation is: (1)
      ingenuously confident of the power of multivariate statistical methods; (2) naive
      about the interactive nature of the clinical relationship.

PMID- 1390359
TI  - Comments on the objective analysis of motivation and psychotherapy.
AB  - There are several important issues raised in the paper by Cattell and in the
      comments upon it: the empirical status of the Cattell factors; the experimental
      verification of factors; difficulties with confirmatory analysis and the value of
      P-analysis. The relevance of these points is explicated in this paper.

PMID- 1390361
TI  - The psychological well-being of infertile women after a failed IVF attempt: the
      effects of coping.
AB  - One hundred infertile women and 73 female controls completed three measures of
      psychological well-being (depression, self-esteem and self-confidence) on two
      occasions (Times 1 and 2), coinciding with the beginning and end of a failed IVF
      attempt by the infertile women. At Time 2, the IVF women were also asked to
      indicate whether they had used a number of different coping responses, in
      relation to dealing with their failed IVF attempt. As predicted, IVF women were
      more depressed and had lower self-esteem than controls prior to the treatment
      cycle, and both before and after the treatment cycle they were less self
      confident. After the failed IVF procedure, IVF women were more depressed and had
      lower levels of self-esteem than they did prior to the treatment cycle. In terms
      of the effects of coping on the post-attempt well-being of the IVF women, the use
      of problem-focused coping was associated with high levels of well-being, while
      the use of avoidance coping and seeking social support was associated with low
      levels of well-being.

PMID- 1390360
TI  - Causal beliefs about depression in depressed patients, clinical psychologists and
      lay persons.
AB  - Non-depressed lay persons have been shown to have extensive and accurate
      knowledge about depression (Rippere, 1977, 1980 a, b, 1981 a) that is underpinned
      by a structure that resembles current academic theories of the disorder (Furnham
      & Kuyken, 1991). In this study a semi-structured interview schedule and a number
      of rating scales were used to determine and compare the nature and extent of
      depressed patients', clinical psychologists', and lay persons' beliefs about the
      causes of depression. We confirmed that depressed patients and non-depressed lay
      persons alike have relatively extensive beliefs about the causes of depression
      which are comparable to those held by clinical psychologists. However, depressed
      patients tend to endorse biological explanations of the causes of depression to a
      greater extent than clinical psychologists. In contrast, clinical psychologists
      assign a more important causal role to unconscious processes and childhood
      vulnerability factors than do either depressed patients or non-depressed lay
      controls.

PMID- 1390362
TI  - Group therapy in the management of epilepsy.
AB  - A pilot project using group therapy with patients from an epilepsy clinic is
      described. Observations of the group show that members were able to discuss their
      feelings about having epilepsy, and the difficulties the disorder caused in all
      areas of their lives, and to tolerate and learn from seizures which took place
      during group meetings. The greatest benefit was meeting others with epilepsy and
      sharing experiences in an environment that was not overprotective or overanxious,
      in contrast to their usual surroundings. The author suggests that groups of a
      similar nature could be a useful addition to the management of people with
      epilepsy.

PMID- 1390363
TI  - Fibronectin as a prognostic indicator in portal hypertension.
AB  - Plasma fibronectin levels were measured in 33 patients with portal hypertension
      and compared with modified Child's grading and a previously described prognostic
      index. Outcome at one year from blood sampling was recorded. Mean plasma
      fibronectin level was 304.1 mg/ml (sem 24.3) and significantly lower levels were
      found in patients who had had a variceal bleed within the previous seven days.
      Plasma fibronectin levels tended to be lower in patients with poor liver function
      as assessed by modified Child's grading but this did not achieve statistical
      significance. Plasma fibronectin alone was not an accurate predictor of one year
      survival in these patients but only one of seven patients who had a plasma
      fibronectin level below 300 mg/l in association with a poor prognostic index
      survived for one year.

PMID- 1390364
TI  - Radiation stricture of the biliary ducts: an emerging new entity?
AB  - Two patients with stricture of the extrahepatic biliary tree are described. Both
      patients presented with a clinical picture of obstructive jaundice one to two
      years following radiotherapy for a malignant condition. As no recurrent tumour
      was detected in either of the patients the strictures were considered to be the
      result of radiation therapy. Bilio-enteric decompression was performed in both
      patients who are well at follow up one and ten years after the procedure.

PMID- 1390366
TI  - Common bile duct stones: ERCP or surgery?

PMID- 1390367
TI  - Does metoclopramide reduce variceal pressure?

PMID- 1390365
TI  - Percutaneous aspiration, lavage and antibiotic instillation. New approach in the
      management of acute cholecystitis failing to respond to conservative management.

PMID- 1390368
TI  - The role of percutaneous transjugular portosystemic shunts.

PMID- 1390369
TI  - Studies in intestinal parasitic disease agents in stools of people in a rural
      area of Nigeria.
AB  - A summary of 300 villagers who reported at the Parasitology Laboratory of the
      School of Medical Laboratory Technology (S.M.L.T) Vom, Plateau State, Nigeria was
      carried out for the presence of parasites' cysts, eggs, or larva. Of the 300
      faecal samples examined using the light microscope after formal-ether
      centrifugation, 127 (42.3%) harboured one or more parasites. The parasites
      identified and their prevalent rates were: Entamoeba coli (19.0%) Necator
      americanus (17.0%); Entamoeba histolytica (4.7%); Schistosoma mansoni (3.0%);
      Giardia lamblia (2.3%); Trichuris trichuria (1.7%); Trichomonas hominis (1.0%);
      Ascaris lumbricoides (0.7%); Hymenolepsis nana (0.3%) Endolimax nana o. 3%);
      stercoralis (0.23%), and Iodamoeba butschlii (0.3%). The overall infection was
      22.7% for the males and 19.7% for the females. Incidence was highest in villagers
      aged between 21 and 40 years.

PMID- 1390370
TI  - Factors that may contribute to death from typhoid infection among Nigerians.
AB  - Ninety-five cases of typhoid infection seen at autopsy at the University College
      Hospital, Ibadan, over a 10-year period were reviewed. They constituted 2.7% of
      3,556 autopsies performed during this period. Apart from the associated
      conditions such as sickle cell disease, aplastic anaemia, schistosomiasis, liver
      cirrhosis and pregnancy which may lower the patients' immunity, a delay in
      seeking medical care, misdiagnoses, inappropriate therapy and a high complication
      rate were some of the factors that would appear to contribute to mortality.
      Therefore, in order to reduce death associated with these factors, it is
      essential to improve the health education of the people stressing the importance
      of personal communal hygiene and prompt hospital attendance from the onset of
      illness. There must also be improved clinical awareness of the disease to ensure
      early diagnosis and treatment. These are of great importance as the disease is
      treatable.

PMID- 1390371
TI  - Kerosene poisoning in childhood: a 6-year prospective study at the University of
      Ilorin Teaching Hospital.
AB  - In a 6-year prospective study of kerosene poisoning in children admitted to the
      Department of Paediatrics, University of Ilorin Teaching Hospital (UITH), between
      January 1982 and December 1987, 109 cases were seen. They were aged 6 months to 9
      years, with a male: female ratio of 1.8:1. Majority (79.8%) were below 2 years.
      Many households (52.3%) stored the agent in familiar beverage or household
      containers placed on kitchen or bedroom floors, within easy reach of infants and
      toddlers. Seventy-six (69.7%) cases had home remedies, palm oil being the most
      common accounting for 55.3%. More than half of the cases (56.9%) presented within
      12 hours of the accident due to persistent cough and dyspnoea. Respiratory
      complications viz pneumonia, pleural effusion and pulmonary oedema were the most
      common, evident in 67.3% of those who had chest radiographs. Approximately, three
      quarters (74.3%) of patients with radiologic abnormalities had palm oil alone or
      in combination with milk as home remedies. Severity of poisoning was influenced
      by the type of home remedy and the interval between accident and admission (P
      less than 0.05; P less than 0.01 respectively). Presence of radiological or CNS
      abnormality or both was associated with a higher morbidity. The only death in the
      study had complications referable to both systems. Ways of minimizing the risk of
      kerosene poisoning and its attendant morbidity are discussed.

PMID- 1390372
TI  - Computerised axial tomographic scanning in neuropsychiatric disorders.
AB  - The invention of the computerised tomography scanner - a product of modern bio
      medical technology has significantly enhanced the diagnostic capability of
      physicians in the management of brain disorders such as cerebral atrophy,
      subdural haematoma, tuberous sclerosis, small calcifications and small
      intravascular clots. It is also useful in radiotherapy planning. The advantages
      of the CT scanner over the older conventional techniques, namely
      pneumoencephalography and arteriography are accuracy, reliability, and simplicity
      of operation. The major limitation is its diminished ability relative to
      angiography to precisely detect vascular disease, e.g. aneurysm. Furthermore, it
      is expensive and not precise in the differentiation of benign from malignant
      lesions. Despite the development of newer neuro-radiological equipment such as
      position emission tomography (PET) and nuclear magnetic resonance, the CT scanner
      remains a most invaluable diagnostic tool and should be given priority
      consideration in health vote allocation.

PMID- 1390373
TI  - Pattern of pedestrian injuries from road traffic accidents in Nigerians.
AB  - A prospective study of 108 Nigerian pedestrian road traffic accident (RTA)
      victims was conducted at the University of Ilorin Teaching Hospital in Nigeria
      between 1983 and 1984. Peak incidence occurred among 6 to 12 year old children
      while male/female ratio was 2.4/1. Multiple injuries occurred in 51.9% of the
      patients involving most frequently the chest with other body parts. Fifty-two
      patients (48.1%) required minor and major operations while the remaining 51.9%
      were treated non-operatively. Mortality was 12.0%. Only two of the thirteen dead
      patients were children. Socio-cultural, economic and clinical factors
      contributing to pedestrian RTA morbidity and mortality are reviewed as a basis
      for recommending preventive measure.

PMID- 1390374
TI  - Infantile hypertrophic pyloric stenosis in Ghana.
AB  - In a retrospective study of 84 Ghanaian infants with hypertrophic pyloric
      stenosis seen over a 15-year period between 1974 and 1988, the male/female
      incidence ratio was 9:1. First-born infants constituted 23.8% of the patient
      population. The incidence of associated congenital anomalies and jaundice were
      10.7% and 3.6% respectively. About 33.3% of the infants started vomiting within
      the first week of life. The peak-age of presentation and diagnosis was between
      the second and sixth weeks of life. The operative mortality was 3.6%.

PMID- 1390375
TI  - Assessment of minidose intrathecal morphine for analgesia after hemorroidectomy.
AB  - The efficacy of 0.5kg intrathecal morphine was tested on 10 patients who had
      hemorrhoidectomy performed at the University College Hospital (UCH), Ibadan. They
      were anesthetized with 3 mls of 0.5% intrathecal bupivacine to which 0.5mg of
      morphine was added. Another 14 patients had intrathecal 3 mls of 0.5% bupivacine
      with normal saline. Post-operative analgesia was prolonged in the opiate group
      compared to the saline group up to 8th post-operative hour. Narcotic analgesic
      requirement was much less in the opiate group. There were no serious
      complications in either group. In view of the excellent analgesia in the
      immediate post-operative period and absence of delayed respiratory depression
      usually associated with higher doses of spinal opiates it is recommended that use
      of the technique be encouraged in similar surgical patients for pain relief.

PMID- 1390376
TI  - Kaposis sarcoma report of a case with exclusive oral involvement.
AB  - A case of Kaposis sarcoma presenting exclusively in the oral cavity is reported.
      Exclusive oral presentation of Kaposis sarcoma is considered extremely rare. At
      the U.C.H. Ibadan, a total of one hundred and two cases of Kaposis sarcoma were
      seen in the last 24 years. None of these presented exclusively or concomitantly
      in the oral cavity, until this case under review. The clinical and histological
      difficulties that were encountered in diagnosing this exclusive oral presentation
      are discussed. Literature review on possible pathogenesis is highlighted.

PMID- 1390378
TI  - Invasive cervical carcinoma in two sisters.
AB  - The occurrence of pre-invasive cervical carcinoma among siblings and in mother
      daughter pairs has been reported previously in Europe. Invasive cervical cancer
      diagnosed in two Nigerian sisters within a period of three months is reported. It
      is suggested that sisters and daughters of patients with cervical cancer may be
      at a higher risk of developing the lesion because of similar socio-economic and
      cultural backgrounds and should therefore have regular cervical screening.

PMID- 1390377
TI  - Quintuplet pregnancy case report.

PMID- 1390379
TI  - Acute intermittent [corrected] porphyria. An often forgotten diagnosis in acute
      abdomen.
AB  - Three cases of Acute Intermittent Porphyria (AIP) are described. All presented
      with acute intermittent abdominal pains. One had grand-mal epilepsy as well. Two
      were diagnosed by chance. In the third case the diagnosis was thought of. It is
      suggested that AIP should always be considered as one of the differential
      diagnosis in Acute Abdomen in West Africa.

PMID- 1390380
TI  - Weaning practices in Ilorin community, Nigeria.
AB  - The paper examines the knowledge, attitude and practice of weaning in 516 mothers
      in Ilorin community, the capital of Kwara State of Nigeria. Women with a higher
      level of education and family income breastfed for a shorter period, and tended
      to wean earlier than the illiterate and low income group (p less than 0.05). Two
      hundred and twenty-eight mothers (44.2%) had commenced weaning by 3 months of age
      while 433 (83.9%) had done so by 6 months. Hunger, indicated by crying after a
      feed or demanding more frequent feeds, was the commonest reason for weaning
      (36.2%). Pap (maize or guineacorn gruel), an energy-sparse food remained the
      major weaning food irrespective of socio-economic characteristics. Fortification
      of pap was positively influenced by a high family income and education.
      Diarrhoea, associated with bottlefeeding or cow-pea diet, was the major cause of
      morbidity reported during weaning (55.8%). Ways of improving child health during
      the weaning period are suggested.

PMID- 1390381
TI  - The neurotensin-related hexapeptide LANT6 is found in retinal ganglion cells and
      in their central projections in pigeons.
AB  - Previous biochemical and immunohistochemical studies have shown that the
      neurotensin-related hexapeptide LANT6 is widespread and abundant in the avian
      nervous system. In the present study, immunohistochemical techniques were used to
      show that LANT6 is present in numerous cells of the retinal ganglion cell layer
      in pigeons. Consistent with the possibility that these LANT6+ retinal cells might
      be retinal ganglion cells, it was found that (1) the distribution of LANT6+
      fibers and terminals in the central retinal target areas matched the distribution
      of central retinal projections; (2) the LANT6+ fibers and terminals are
      eliminated from retinal target areas by transection of the contralateral optic
      nerve; and (3) LANT6+ retinal cells in the ganglion cell layer can be
      retrogradely labeled by injections of fluorogold in the tectum. These results
      suggest that LANT6 may be utilized as a neuroactive substance by the central
      terminals of numerous retinal ganglion cells in birds. Similar anatomical
      findings have been previously reported for members of several other vertebrate
      groups, giving rise to the possibility that LANT6 (or its homologues in
      nonavians) may be a phylogenetically ubiquitous neuroactive substance used by
      retinal ganglion cells.

PMID- 1390382
TI  - Visual-discrimination deficits after lesions of the centrifugal visual system in
      pigeons (Columba livia).
AB  - The effects of bilateral lesions of the centrifugal visual system (CVS) on the
      visual-discrimination capacity were studied in pigeons. Three different
      behavioral experiments, each testing different aspects of visual analysis, were
      performed. In the first two experiments, a grain-grit discrimination task and a
      visual-acuity determination, stimuli were presented in the frontal binocular
      visual field. A third experiment investigated the early detection of slow moving
      objects, introduced into the monocular lateral visual field. After bilateral
      lesions in the nucleus isthmo-opticus (ION) and in the ectopic nucleus isthmo
      opticus (EION), a multiple linear regression analysis was employed to correlate
      the postoperative performance in all three tasks with the amount of structure
      loss within ION and EION. Deficits in the grain-grit discrimination procedure
      were a function of the ION lesion extent and did not depend on EION damage. Thus,
      these two structures could be functionally differentiated for the first time.
      Neither the ION nor the EION seems to be involved in visual-acuity performance or
      the early detection of large shadows moving forward through the visual field. Our
      data support the hypothesis that the CVS is involved in pecking and food
      selection among static stimuli at a short viewing distance in ground-feeding
      birds such as pigeons and chickens.

PMID- 1390383
TI  - Spectral properties of short-wavelength (blue) cones in the turtle retina.
AB  - Long- and medium-wavelength cones in the turtle retina participate in complex
      neural interactions. They are coupled via excitatory pathways to other cones and
      receive negative feedback inputs from luminosity-type horizontal cells. Little
      information has been collected on the S- (short-wavelength or blue) cones because
      they are scarce in the turtle retina and of smaller dimensions compared to the
      other cone types. In this paper, flash sensitivity action spectra and
      photoresponses of seven turtle S-cones were measured in the dark-adapted state
      and during chromatic background illuminations. The desensitizing action of
      monochromatic background lights was not uniform across the visible spectrum. A
      red background was most effective in desensitizing the S-cones to long-wavelength
      stimuli while a blue background light produced its strongest action on the
      photoresponses elicited by short-wavelength stimuli. The effects of chromatic
      adaptation on the S-cone action spectrum and on the kinetics of the small
      amplitude photoresponses suggested that the S-cones in the turtle retina were
      involved in complex neural interactions. These included excitatory inputs
      probably originating in neighboring L-cones and inhibitory long-wavelength inputs
      probably mediated by L-type horizontal cells.

PMID- 1390384
TI  - Development of vernier acuity and grating acuity in normally reared monkeys.
AB  - The developmental time courses for vernier acuity and grating acuity were
      measured longitudinally in infant Macaca nemestrina monkeys. Behavioral
      measurements of vernier and grating acuity were made at regular intervals during
      development. Near birth, grating acuity is relatively more mature than vernier
      acuity. The proportional rate of vernier acuity development is faster than that
      for grating acuity. During the course of development, grating acuity improves
      approximately 15-fold whereas vernier acuity improves about 60-fold. Both visual
      functions approach adult levels at about the same age, around 40 weeks
      postnatally. Although grating acuity develops about four times faster in monkeys
      than in humans, vernier acuity development in monkeys and humans does not appear
      to reflect the same relationship. Adult levels of vernier acuity for the monkeys
      are about a factor of 2 poorer than are typically reported for humans. The
      differential development of vernier acuity and grating acuity does not
      necessarily reflect development at different levels of the visual system.

PMID- 1390385
TI  - Effect of strabismus on the development of vernier acuity and grating acuity in
      monkeys.
AB  - The effect of experimental strabismus on the development of vernier acuity and
      grating acuity was studied in Macaca nemestrina monkeys. Six monkeys were studied
      longitudinally beginning near 10 days after birth. Four of the six monkeys
      developed amblyopia. As is true for human strabismic amblyopes, the deficit in
      vernier acuity was larger than the deficit in grating acuity in the amblyopic
      monkeys. The developmental data reveal that this differential disruption of
      vernier acuity can be understood as a result of a slowed developmental process
      associated with amblyopia.

PMID- 1390386
TI  - Oculomotor localization relies on a damped representation of saccadic eye
      displacement in human and nonhuman primates.
AB  - The oculomotor system has long been thought to rely on an accurate representation
      of eye displacement or position in a successful attempt to reconcile a stationary
      target's retinal instability (caused by motion of the eyes) with its
      corresponding spatial invariance. This is in stark contrast to perceptual
      localization, which has been shown to rely on a sluggish representation of eye
      displacement, achieving only partial compensation for the retinal displacement
      caused by saccadic eye movements. Recent studies, however, have begun to case
      doubt on the belief that the oculomotor system possess a signal of eye
      displacement superior to that of the perceptual system. To verify this, five
      humans and one monkey (Macaca nemestrina) served as subjects in this study of
      oculomotor localization abilities. Subjects were instructed to make eye
      movements, as accurately as possible, to the locations of three successive visual
      stimuli. Presentation of the third stimulus (2-ms duration) was timed so that it
      fell before, during, or after the subject's saccade from the first stimulus to
      the second. Localization errors in each subject (human and nonhuman) were
      consistent with the hypothesis that the oculomotor system has access to only a
      damped representation of eye displacement--a representation similar to that found
      in perceptual localization studies.

PMID- 1390387
TI  - A coupled network for parasol but not midget ganglion cells in the primate
      retina.
AB  - Intracellular injections of Neurobiotin were used to determine whether the major
      ganglion cell classes of the macaque monkey retina, the magnocellular-projecting
      parasol, and the parvocellular-projecting midget cells showed evidence of
      cellular coupling similar to that recently described for cat retinal ganglion
      cells. Ganglion cells were labeled with the fluorescent dye acridine orange in an
      in vitro, isolated retina preparation and were selectively targeted for
      intracellular injection under direct microscopic control. The macaque midget
      cells, like the beta cells of the cat's retina, showed no evidence of tracer
      coupling when injected with Neurobiotin. By contrast, Neurobiotin-filled parasol
      cells, like cat alpha cells, showed a distinct pattern of tracer coupling to each
      other (homotypic coupling) and to amacrine cells (heterotypic coupling). In
      instances of homotypic coupling, the injected parasol cell was surrounded by a
      regular array of 3-6 neighboring parasol cells. The somata and proximal dendrites
      of these tracer-coupled cells were lightly labeled and appeared to costratify
      with the injected cell. Analysis of the nearest-neighbor distances for the
      parasol cell clusters showed that dendritic-field overlap remained constant as
      dendritic-field size increased from 100-400 microns in diameter. At least two
      amacrine cell types showed tracer coupling to parasol cells. One amacrine type
      had a small soma and thin, sparsely branching dendrites that extended for 1-2 mm
      in the inner plexiform layer. A second amacrine type had a relatively large soma,
      thick main dendrites, and distinct, axon-like processes that extended for at
      least 2-3 mm in the inner plexiform layer. The main dendrites of the large
      amacrine cells were closely apposed to the dendrites of parasol cells and may be
      the site of Neurobiotin transfer between the two cell types. We suggest that the
      tracer coupling between neighboring parasol cells takes place indirectly via the
      dendrites of the large amacrine cells and provides a mechanism, absent in midget
      cells, for increasing parasol cell receptive-field size and luminance contrast
      sensitivity.

PMID- 1390388
TI  - Subcortical connections of visual areas MST and FST in macaques.
AB  - To examine the subcortical connections of the medial superior temporal and fundus
      of the superior temporal visual areas (MST and FST, respectively), we injected
      anterograde and retrograde tracers into 16 physiologically identified sites
      within the two areas in seven macaque monkeys. The subcortical connections of MST
      and FST were found to be very similar. Both areas were found to be reciprocally
      connected with the pulvinar, mainly with its medial subdivision, and with the
      claustrum. Nonreciprocal projections from both MST and FST were consistently
      found in the striatum (caudate and putamen), reticular nucleus of the thalamus,
      and the pontine nuclei. The labeled terminals in the pons were in the
      dorsolateral, lateral, dorsal, and peduncular nuclei. Additional nonreciprocal
      projections were found in one MST and one FST case to the nucleus of the optic
      tract, and, in one FST case, to the lateral terminal nucleus. Finally, three
      cases showed a nonreciprocal projection to FST from the basal forebrain. The
      subcortical structures containing label following MST and FST injections were
      largely the same as those labeled after injections of the middle temporal visual
      area (MT), but the label within each structure after MST and FST injections was
      more widespread than that from MT, overlapping the distribution of label that has
      been reported after injections of parietal visual areas. This finding is
      consistent with the known contributions of MST and FST to the functions of
      parietal cortex, such as eye-movement control.

PMID- 1390389
TI  - Binocular depth perception following early experience with interocular torsional
      disparity.
AB  - The relationship between the behavioral and physiological consequences of rearing
      with optically induced cyclotropia was assessed. Beginning at the age of 4 weeks,
      kittens wore goggles that rotated the visual field in opposite directions in each
      eye for several hours each day over a period of several weeks. The amounts of
      interocular rotation were 0 deg (control), 16 deg, and 32 deg. Subsequently, they
      were tested to determine their monocular and binocular depth thresholds and, in
      some cases, visual acuity. In several kittens recordings were also made from the
      visual cortex. Binocular performance of all kittens in the 0-deg condition and
      three out of six kittens in the 16-deg condition was comparable to, although
      slightly lower than, that of normally reared kittens. In contrast, none of the 32
      deg kittens showed any evidence of the binocular superiority that would suggest
      the presence of stereopsis. Extracellular unit recordings from the visual cortex
      confirmed our earlier results with goggle-reared kittens. In 16-deg kittens, the
      distribution of the cells' preferred interocular disparities (IOD) in receptive
      field orientation showed a compensating shift so that the mean matched the
      experienced rotational disparity. In the 32-deg kittens, binocularity was greatly
      disrupted and there was no compensatory shift in the IOD distribution. Two 32-deg
      kittens were afforded 3 years of subsequent normal visual experience. Both the
      behavioral and the physiological findings were unaffected by normal visual
      exposure in adulthood. Control measurements of acuity indicated that any deficits
      in depth perception were not due to reduced spatial-resolution abilities. The
      data indicate that the kitten visual system is able to maintain functional
      binocularity sufficient to subserve a moderate level of stereoacuity with
      interocular rotations of up to at least 16 deg.

PMID- 1390390
TI  - Contacts of dopaminergic interplexiform cells in the outer retina of the blue
      acara.
AB  - Dopaminergic interplexiform cells in the retina of the blue acara were
      investigated using an antiserum against tyrosine hydroxylase and PAP
      visualization. In whole-mount preparations, we observed a homogeneous
      distribution of cell bodies throughout the retina without any indication of
      regional specialization. At the fine and ultrastructural level, we studied the
      morphology of labeled telodendria within the outer plexiform layer. Apart from
      contacts with horizontal cell perikarya and bipolar cell dendrites, we observed
      direct contacts, mostly in the form of close appositions, with cone pedicles and
      rod spherules. Quantitative evaluation and reconstruction of serial sections
      showed that all cone pedicles and most rod terminals were approached in this way.
      The dopaminergic pathway terminating on horizontal cells and photoreceptors is
      discussed with respect to the localization of dopamine receptors in the outer
      retina, and the control of adaptive changes such as retinomotor movements,
      spinule formation, and horizontal cell coupling.

PMID- 1390391
TI  - The effect of dopamine depletion on light-evoked and circadian retinomotor
      movements in the teleost retina.
AB  - The retinae of lower vertebrates undergo a number of structural changes during
      light adaptation, including the photomechanical contraction of cone myoids and
      the dispersion of melanin granules within the epithelial pigment. Since the
      application of dopamine to dark-adapted retinae is known to produce morphological
      changes that are characteristic of light adaptation, dopamine is accepted as a
      casual mechanism for such retinomotor movements. However, we report here that in
      the teleost fish, Aequidens pulcher, the intraocular injection of 6
      hydroxydopamine (6-OHDA), a substance known to destroy dopaminergic retinal
      cells, has no effect on the triggering of light-adaptive retinomotor movements of
      the cones and epithelial pigment and only slightly depresses the final level of
      light adaptation reached. Furthermore, the retina continues to show circadian
      retinomotor changes even after 48 h in continual darkness that are similar in
      both control and 6-OHDA injected fish. Biochemical assay and microscopic
      examination showed that 6-OHDA had destroyed dopaminergic retinal cells. We
      conclude, therefore, that although a dopaminergic mechanism is probably involved
      in the control of light-induced retinomotor movements, it cannot be the only
      control mechanism, nor can it be the cause of circadian retinomotor migrations.
      Interestingly, 6-OHDA injected eyes never reached full retinomotor dark
      adaptation, suggesting that dopamine has a role to play in the retina's response
      to darkness.

PMID- 1390392
TI  - The circadian component of spinule dynamics in teleost retinal horizontal cells
      is dependent on the dopaminergic system.
AB  - During the light phase of a light/dark cycle, dendrites of teleost cone
      horizontal cells display numerous finger-like projections, called spinules, which
      are formed at dawn and degraded at dusk, and are thought to be involved in
      chromatic feedback processes. We have studied the oscillations of these spinules
      during a normal light/dark cycle and during 48 h of constant darkness in two
      groups of strongly rhythmic, diurnal fish, Aequidens pulcher. In one group the
      retinal dopaminergic system had been destroyed by the application of 6-OHDA,
      while in the other (control) group, the dopaminergic system was intact. In
      control fish, oscillations of spinule numbers were observed under both normal and
      constant dark conditions, indicating the presence of a robust circadian rhythm.
      However, spinule dynamics were severely affected by the absence of retinal
      dopamine. During the normal light phase, the number of spinules in 6-OHDA
      injected retinae was strongly reduced, and throughout continual darkness, spinule
      formation was almost completely suppressed. These results indicate that dopamine
      is essential for both light-evoked and circadian spinule formation; furthermore,
      we conclude that there is no circadian oscillator within horizontal cells
      controlling the formation of spinules.

PMID- 1390394
TI  - Localization of actin filaments and microtubules in the cells of the Limulus
      lateral and ventral eyes.
AB  - The ommatidia of the lateral eye of the horseshoe crab, Limulus polyphemus,
      undergo rhythmic changes in structure that are driven by diurnal lighting and
      efferent neural activity from a circadian clock in the brain. This study uses
      cytochemical probes to investigate the cytoskeletal elements mediating these
      responses and to develop models for their control. Antibodies to actin and
      phallodin, a specific F-actin probe, label the rhabdom of lateral eye ommatidia,
      the cone cells of the ommatidial aperture, the ommatidial sheath, and the
      peripheral regions of the photoreceptor (retinular cell) cytoplasm. These probes
      also label the rhabdomere of ventral photoreceptors. Antibodies to tubulin label
      the eccentric cell dendrite and soma in each lateral eye ommatidium, the cone
      cells of the aperture, and the peripheral retinular cell cytoplasm. Models are
      proposed for the cytoskeletal mechanisms involved in controlling aperture and
      rhabdom shape, pigment movement, and shedding of rhabdomeral membrane.

PMID- 1390393
TI  - Effects of serotonergic agonists and antagonists on ganglion cells in the
      goldfish retina.
AB  - Extracellular recordings were made from the isolated goldfish retina during
      superfusion with various serotonergic agonists and antagonists to determine the
      effects of these drugs on the maintained activity and response properties of the
      ganglion cells. Superfusion of the retina with serotonin (25-500 microM)
      increased the maintained activity of OFF-center ganglion cells and decreased the
      maintained activity of ON-center ganglion cells. In addition, serotonin also
      attenuated the excitatory responses to annular stimuli, suggesting a decrease in
      the strength of surround input to the ganglion cells. The effects of serotonin on
      OFF-center ganglion cells were mimicked by the nonselective 5-HT1 agonist 5-MeOT
      and the 5-HT1A receptor agonist 8-OH-DPAT, while only 5-MeOT mimicked the action
      of serotonin on ON-center ganglion cells. The effects of exogenously applied
      serotonin on the ganglion cells could be blocked by the mixed 5-HT1/5-HT2
      receptor antagonist methysergide but not by the 5-HT2 receptor antagonist
      mianserin or the dopamine receptor antagonist haloperidol. These results support
      previous anatomical and biochemical evidence that serotonin functions in a
      neurotransmitter or neuromodulatory role in the teleost retina and suggest that
      serotonin may be involved in modulating the maintained activity and surround
      input to the ganglion cells. The results also indicate that two different types
      of receptors may mediate the actions of serotonin in the ON and OFF pathways,
      respectively.

PMID- 1390395
TI  - Serotonin synthesis and accumulation by neurons of the anuran retina.
AB  - Serotonin-synthesizing and serotonin-accumulating neurons were studied in the
      retinas of Xenopus laevis and Bufo marinus. All previously identified cell types
      exhibiting serotonin-like immunoreactivity (SLI) were labeled by intravitreal
      injection of 5,7-dihydroxytryptamine (5,7-DHT). They included two amacrine cell
      types (large and small) in both species, and one bipolar cell type in Xenopus.
      Incubation of retinas in culture medium in the ambient light reduced SLI in
      amacrine cells and enhanced the labeling in bipolar cells. After incubation, some
      photoreceptor cell bodies and large numbers of outer segments also displayed SLI
      in both species. Incubation with the serotonin-uptake inhibitor, fluoxetine,
      reduced immunolabeling in bipolar cells and outer segments to the level in the
      untreated retinas. Both large SLI and 5,7-DHT-accumulating amacrine cells in
      Xenopus and Bufo were labeled with an antibody raised against phenylalanine
      hydroxylase (PH), which binds to tryptophan 5-hydroxylase, one of the
      synthesizing enzymes for serotonin. Small SLI and 5,7-DHT-accumulating amacrine
      cells in both species represented two populations, one with and the other without
      PH-like immunoreactivity (PH-LI). The anti-PH antibody failed to label any SLI or
      5,7-DHT-accumulating bipolar cells in Xenopus. These observations indicate that
      all large and some small SLI amacrine cells in the retinas of Xenopus and Bufo
      synthesize serotonin, while other small SLI amacrine, bipolar and photoreceptor
      cell bodies, and outer segments only accumulate serotonin.

PMID- 1390396
TI  - Enkephalin-immunoreactive ganglion cells in the pigeon retina.
AB  - A small number of enkephalin-like immunoreactive cells were observed in the
      ganglion cell layer of the pigeon retina. Many of these neurons were identified
      as ganglion cells, since they were retrogradely labeled after injections of
      fluorescent latex microspheres in the contralateral optic tectum. These ganglion
      cells were mainly distributed in the inferior retina, and their soma sizes ranged
      from 12-26 microns in the largest axis. The enkephalin-containing ganglion cells
      appear to represent only a very small percentage of the ganglion cells projecting
      to the optic tectum (less than 0.1%). Two to 7 weeks after removal of the neural
      retina, there was an almost complete elimination of an enkephalin-like
      immunoreactive plexus in layer 3 of the contralateral, rostrodorsal optic tectum.
      These data provide evidence for the existence of a population of enkephalinergic
      retinal ganglion cells with projections to the optic tectum.

PMID- 1390397
TI  - Area 17 lesions deactivate area MT in owl monkeys.
AB  - The middle temporal visual area, MT, is one of three major targets of the primary
      visual cortex, area 17, in primates. We assessed the contribution of area 17
      connections to the responsiveness of area MT neurons to visual stimuli by first
      mapping the representation of the visual hemifield in MT of anesthetized owl
      monkeys with microelectrodes, ablating an electrophysiologically mapped part of
      area 17, and then immediately remapping MT. Before the lesions, neurons at
      recording sites throughout MT responded vigorously to moving slits of light and
      other visual stimuli. In addition, the relationship of receptive fields to
      recording sites revealed a systematic representation of the contralateral visual
      hemifield in MT, as reported previously for owl monkeys and other primates. The
      immediate effect of removing part of the retinotopic map in area 17 by gentle
      aspiration was to selectively deactivate the corresponding part of the visuotopic
      map in MT. Lesions of dorsomedial area 17 representing central and paracentral
      vision of the lower visual quadrant deactivated neurons in caudomedial MT
      formerly having receptive fields in the central and paracentral lower visual
      quadrant. Most neurons at recording sites throughout other parts of MT had normal
      levels of responsiveness to visual stimuli, and receptive-field locations that
      closely matched those before the lesion. However, neurons at a few sites along
      the margin of the deactivated zone of cortex had receptive fields that were
      slightly displaced from the region of vision affected by the lesion into other
      parts of the visual field, suggesting some degree of plasticity in the visual
      hemifield representation in MT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390398
TI  - Visual thresholds in albino and pigmented rats.
AB  - Albino rats have recently been reported to have increment thresholds against dim
      backgrounds that are two log units higher than those of pigmented rats. We, on
      the other hand, have failed to confirm these differences using electroretinogram
      b-waves and pupillary light reflexes. This paper reports on experiments using
      evoked potentials from cortex and colliculus and single-unit recordings from
      colliculus. We recorded visual-evoked potentials from cortex and superior
      colliculus in the strains of albino (CD) and pigmented (Long-Evans) rats used in
      the earlier studies. Thresholds were determined on eight fully dark-adapted
      animals by extrapolating intensity-response curves to the point at which there
      was zero evoked potential. The average dark-adapted threshold for the visual
      evoked cortical potential was -5.6 log cd/m2 in pigmented and -5.80 log cd/m2 in
      albino animals. The average dark-adapted threshold for the superior colliculus
      evoked response was -5.54 log cd/m2 in pigmented and -5.84 log cd/m2 in albinos.
      The differences were not statistically significant. On the same apparatus, the
      average absolute threshold for three human observers was -5.3 log cd/m2, a value
      close to the rat dark-adapted thresholds. Thus, visual-evoked cortical potentials
      and superior collicular evoked potentials failed to confirm the report of higher
      dark-adapted thresholds for albinos. In addition, we find that single units in
      superior colliculus in the albino rat respond to very dim flashes.

PMID- 1390399
TI  - Contemporary professional issues in research on schizophrenia.

PMID- 1390400
TI  - Visual orienting in schizophrenia.
AB  - Patients with schizophrenia demonstrate a variety of attentional impairments
      which have proven difficult to relate to specific neural systems. Posner et al.
      (1988) reported an asymmetric slowing of right visual field orienting in
      schizophrenia similar to that observed in patients with parietal lesions. We
      examined the visual orienting performance of 19 patients and controls using two
      different versions of the Posner paradigm. In overall ANOVAs we found main
      effects of group, cue condition, and delay interval. However, we did not observe
      any main effect of visual field or interactions involving visual field. There was
      some evidence of an asymmetric cost of invalid cues similar to those reported by
      Posner et al. The bulk of data suggests bilateral attentional deficits.

PMID- 1390401
TI  - Gender differences in the clinical expression of schizophrenia.
AB  - Gender differences have been reported for a variety of clinical measures in
      patients with schizophrenia. Clinical characterization may be helpful in
      identifying symptom clusters which can then be linked to underlying brain
      function. In this study 74 men and 33 women meeting DSM-IIIR criteria for
      schizophrenia were studied off medication and rated on measures of symptom type
      and severity, as well as premorbid and current function. Men were more severely
      impaired in ratings of negative symptoms, while positive symptoms were not
      significantly different. There were also differences in premorbid and current
      functioning, with women manifesting better social functioning than men.

PMID- 1390402
TI  - Auditory hallucinations in women and men.
AB  - The total population of a community schizophrenia registry sample yielded
      information about the relative lifetime frequency of hallucinations in women and
      men. Whereas hallucinations in non-auditory modalities were equally distributed
      between the two sexes, auditory hallucinations were significantly more common in
      women. These results will be considered in relation to the existing literature on
      hallucinations and gender.

PMID- 1390404
TI  - Sparring over hexagonal keratotomy.

PMID- 1390403
TI  - Pre-frontal structural and functional deficits associated with individual
      differences in schizotypal personality.
AB  - This study tests the hypothesis that pre-frontal deficits underlie schizotypal
      personality in the normal population. Personality measures assessing features of
      DSM-IIIR schizotypal personality disorder (SPD) were related to left and right
      pre-frontal brain area assessed by magnetic resonance imaging (MRI), and
      neuropsychological measures of pre-frontal functioning (Wisconsin Card Sorting
      Task, WCST) in a group of non-institutionalized, unmedicated normal subjects.
      High schizotypal scores were significantly associated with reduced pre-frontal
      area and more WCST perseveration errors; conversely no relationships were
      observed between these pre-frontal measures and measures of psychosis-proneness
      unrelated to SPD traits. Pre-frontal structural findings were not found to be
      mediated by temporal lobe and posterior cortical structural deficits, height,
      weight, socio-economic status, education level and sex differences, while pre
      frontal functional findings were not mediated by non-prefrontal cognitive
      ability. These findings of pre-frontal structural and functional deficits
      associated with schizotypal personality provide some initial converging support
      for a pre-frontal explanation of individual differences in schizotypal
      personality in the general population.

PMID- 1390405
TI  - One-year results of excimer laser photorefractive keratectomy for myopia.
AB  - BACKGROUND: Excimer laser photorefractive keratectomy for the correction of
      myopia is presently under investigation in the United States by the Food and Drug
      Administration (FDA). The Phase II-B FDA study is being conducted on 75 normally
      sighted myopic eyes utilizing three currently available excimer lasers. This
      report presents the 1-year results on 12 myopic eyes treated with the VISX
      excimer laser system at the Ellis Eye Center at Cedars-Sinai Medical Center in
      Los Angeles under the Phase II-B FDA protocol. METHODS: Twelve eyes of 12
      patients with myopia between -1.75 and -5.00 diopters underwent 193 nm
      argon/fluoride excimer laser photorefractive keratectomy. The epithelium was
      mechanically removed, and fixation was accomplished with a suction ring which
      provided nitrogen flow across the corneal surface. The computer controlled
      corneal ablations were 5.00 mm in diameter and were accomplished with an iris
      diaphragm closing from large to small. RESULTS: The preoperative spherical
      equivalent myopia was -3.50 D (SD = 1.02) and the postoperative myopia was -0.25
      (SD = 0.48). Eleven of the 12 patients achieved an uncorrected visual acuity of
      20/30 or better and were corrected to within +/- 0.50 D of emmetropia. All
      corneas demonstrated a mild reticular subepithelial haze which was barely visible
      at 1 year. There were no vision-threatening complications and none of the eyes
      experienced a loss of best corrected visual acuity. CONCLUSIONS: In this small
      trial, the excimer laser appears to be capable of accurately changing the
      refractive power of the cornea for the correction of myopia with minimal side
      effects. Only when larger numbers of patients undergo the procedure will we be
      able to determine the safety and efficacy of photorefractive keratectomy as a
      refractive surgical procedure.

PMID- 1390407
TI  - Combined transverse and interrupted radial keratotomy for compound myopic
      astigmatism.
AB  - BACKGROUND: A variety of patterns of keratotomy are used to correct naturally
      occurring astigmatism. We evaluated straight transverse incisions with
      interrupted radial incisions (jump radials). METHODS: In 32 human eyes with
      naturally occurring astigmatism, we used straight transverse incisions with
      interrupted radial incisions, with or without additional radial keratotomy, to
      correct compound myopic astigmatism. The range of preoperative refractive
      astigmatism was 1.00 to 3.50 D. RESULTS: The mean follow-up time was 15 months
      (range, 12 to 18 months). The average surgically corrected astigmatism was 1.55
      +/- 0.29 D. Eighty-seven percent of the eyes achieved less than 1.00 D of
      astigmatism, and the remaining four eyes retained 1.00 to 1.25 D of astigmatism.
      CONCLUSION: Combined transverse and interrupted radial incisions are effective in
      correcting naturally occurring astigmatism.

PMID- 1390406
TI  - Photokeratitis from subablative 193-nanometer excimer laser radiation.
AB  - BACKGROUND: Photokeratitis is a side effect of UV light exposure whereby the
      corneal epithelium is photochemically injured in a time delayed fashion. UV light
      exposure in the far ultraviolet wavelength range has not previously been
      observed. This study addresses the concern of photokeratitis from subablative 193
      nanometer excimer laser light. METHODS: Dutch belted rabbit corneas were
      irradiated with subablative 193-nanometer excimer laser light over a wide range
      of total energy exposures, and examined by slit lamp biomicroscope for signs of
      photokeratitis. Photokeratitis was identified by epithelial haze and stippling,
      and rose bengal and fluorescein staining at varied time intervals between 1/2 to
      26 hours post exposure. RESULTS: At threshold energy exposures of 1.0 to 1.5
      J/cm2, an immediate superficial epithelial haze was seen which disappeared within
      several hours. At higher energy exposures of 10 J/cm2, a delayed photokeratitis
      with deep rose bengal and even fluorescein staining was seen. This latter delayed
      photokeratitis resembles that of longer UV wavelengths and is due to excimer
      laser fluorescence, whereas the former is a direct response of the 193-nanometer
      light. The percentage of excimer laser light undergoing fluorescence is
      calculated as less than 1%. CONCLUSIONS: The potential side effects and hazards
      of scattered 193-nanometer radiation during excimer laser surgery are extremely
      limited because of the shorter penetration depth of direct excimer radiation and
      the minimal fluorescent emission of longer UV wavelengths for energy exposures
      within the realm of clinical use.

PMID- 1390408
TI  - Report on psychosocial findings and satisfaction among patients 1 year after
      excimer laser photorefractive keratectomy.
AB  - BACKGROUND: The first 26 patients who underwent photorefractive keratectomy with
      an excimer laser in our clinic with a 1-year follow up voluntarily answered a
      questionnaire. METHODS: It was intended to get information about their social
      status, motivation, expectations, and satisfaction with myopic excimer laser
      photorefractive keratectomy. RESULTS: All patients wore corrective lenses before
      surgery; 74% wore no optical correction after the photorefractive keratectomy.
      "To improve general vision" was the highest ranked motivation while "looking
      better" was only of minor importance. Seventy-two percent reported that their
      subjective vision became better; 28% felt that it didn't change, but none
      reported deterioration of subjective vision. Seventy-five percent of the patients
      reported improvement of their lifestyle after surgery, whereas 21% reported no
      change and one patient stated that his lifestyle got worse. On a scale ranging
      from 1 to 5, early postoperative course was painful with a mean score of 2.25;
      the treatment itself was considered as professional (1.42 +/- 0.8) and well done
      (1.54 +/- 0.8). Eighty-four percent of the patients reported that they were
      satisfied with the overall results. CONCLUSIONS: All patients would decide again
      to have photorefractive keratectomy for myopic correction.

PMID- 1390409
TI  - Differences between objective and subjective refractions after radial keratotomy.
AB  - BACKGROUND: In patients who are free of pathology, automatic refractions have
      shown close agreement with the subjective refractions. Clinical experience
      indicated that the normally strong relationship between objective and subjective
      refraction is significantly weakened as a result of radial keratotomy. METHODS:
      Seventy-two patients were refracted before and after surgery, objectively with a
      Humphrey Model #510 autorefractor and subjectively using a binocular refraction
      procedure without cycloplegia. All patients were free of ocular disease and had
      preoperative myopia ranging from -1.00 to -9.00 diopters as determined by the
      subjective spherical equivalent. RESULTS: The results indicated that the
      preoperative difference between the mean spherical automatic and subjective
      refractions was a clinically acceptable 0.25 diopter. However, postoperatively,
      there was a statistically significant difference of 1.25 D with the automatic
      refractor determining more myopic refractions. Subsequent analysis revealed that
      the age of the patient had a direct bearing on this finding with patients less
      than 40 years of age showing more minus in the automatic refraction than patients
      40 years and older. CONCLUSIONS: The postoperative discrepancy between the two
      refractions may be explained by induced optical aberrations and may contribute
      towards the visual fluctuations experienced by radial keratotomy patients. It is
      postulated that the inconsistency in refractive determination is due to optical
      distortion since the age dependence of this effect may be related to the
      reduction of pupil size that occurs with aging. In the radial keratotomy patient,
      the practitioner is faced with a more complex and uncertain refraction that may
      vary according to refractive procedures used and other factors such as pupil
      size.

PMID- 1390410
TI  - Complications of Mersilene sutures in penetrating keratoplasty.
AB  - BACKGROUND: After penetrating keratoplasty, many corneal surgeons adjust sutures
      to reduce astigmatism and then leave the sutures in place indefinitely. Nylon
      sutures can hydrolyze and break years after surgery. In a series of human
      penetrating keratoplasties, we studied the use of polyester (Mersilene) sutures
      that do not hydrolyze. METHODS: We performed two prospective studies of polyester
      (Mersilene) sutures in human penetrating keratoplasty done by one surgeon. Study
      I was a randomized comparison of combined running and interrupted Mersilene and
      nylon sutures in 45 consecutive eyes. Study II was a case series of single
      running Mersilene suture with postoperative adjustment of suture tension to
      manage astigmatism in 23 consecutive eyes. We evaluated the performance of the
      suture and the control of astigmatism. RESULTS: The interrupted running suture
      study demonstrated that interrupted Mersilene sutures were 5.5 times more likely
      to have handling-related complications than nylon interrupted sutures (p = .01);
      in addition, they were three times as likely to have tissue-related complications
      as nylon (p = .16). The running suture study demonstrated an unacceptable
      complication rate of 69% when Mersilene was used as a single adjustable running
      suture. At 6 months postoperatively, the median refractive astigmatism for the
      adjustable cases was 3.37 diopters (mean, 4.03 +/- 2.37 D). Eyes with significant
      suture-related complications were 2.85 times more likely to have greater than
      4.00 D of refractive astigmatism than were eyes without suture-related
      complications. CONCLUSIONS: Mersilene is an undesirable suture for use in
      penetrating keratoplasty.

PMID- 1390411
TI  - Phototherapeutic keratectomy with excimer laser for Reis-Buckler's corneal
      dystrophy.
AB  - Two patients with decreased visual acuity and recurrent epithelial erosions due
      to Reis-Buckler's corneal dystrophy underwent phototherapeutic keratectomy with
      the 193-nanometer excimer laser. Because the epithelial surface was relatively
      smooth prior to surgery, ablations were performed through an intact epithelium.
      Postoperatively, visual acuity was improved and symptoms of erosion decreased in
      both patients. Although no refractive shift was intended with the
      phototherapeutic procedure, both patients were hyperopic following surgery.
      Superficial keratectomy with the 193-nanometer excimer laser thus provides an
      alternative to conventional surgical keratectomy.

PMID- 1390412
TI  - Complications of radial keratotomy: eyes with keratoconus and late wound
      dehiscence.
AB  - BACKGROUND: Radial keratotomy requires a thorough preoperative examination,
      including photokeratography, to detect early keratoconus. METHODS: We compared,
      by light and transmission electron microscopy, the healing process of corneas
      from two patients after radial keratotomy. RESULTS: Clinically, one patient had a
      keratoconus and gained no visual benefit from the radial keratotomy. The other
      patient had a spontaneous corneal perforation at one incision and a hypopyon.
      Histological studies showed a prolonged healing process in both eyes, with a
      persistent epithelial plug. Bowman's layer was also interrupted and retracted in
      both eyes. The inflamed cornea had deep neovascularization. CONCLUSIONS: These
      observations imply that 2 years after surgery, wound healing and, therefore,
      refraction is not stable. The results show the inappropriateness of radial
      keratotomy performed on eyes with keratoconus, with the possible risk of delayed
      corneal perforation.

PMID- 1390413
TI  - Patient preference--contact lens or radial keratotomy?
AB  - BACKGROUND: Past clinical experience has suggested that patients are more
      satisfied after radial keratotomy than when wearing contact lenses. METHODS: One
      hundred patients who had worn contact lenses prior to receiving radial keratotomy
      compared subjectively these two methods for correcting myopia. The postoperative
      follow up ranged from 3 months to 13 years. RESULTS: The vast majority (93%)
      preferred radial keratotomy to the handling of contact lenses. CONCLUSIONS: The
      desire to be independent of optical correction is a sufficient indication for
      refractive surgery.

PMID- 1390415
TI  - Management of hyperopic shift after radial keratotomy.

PMID- 1390414
TI  - Clinical strategies for excimer laser therapeutic keratectomy.
AB  - BACKGROUND: Surgical therapy for superficial corneal scars, dystrophies, or
      surface irregularities with the 193 nm excimer laser shows great promise.
      Depending upon the character of the pathology to be treated, different surgical
      strategies are required. METHODS: Treatment strategies for three patients with
      diverse corneal pathology are presented. Focal surface irregularities are treated
      with small laser spot sizes leaving the epithelium intact. Smooth, uniformly
      distributed subepithelial anterior stromal pathology is best removed with a large
      spot size through intact epithelium. When scattered scarring of variable
      thickness is present, selective epithelial debridement permits improved exposure
      of irregularities in Bowman's layer and the anterior stroma. RESULTS: Guidelines
      for selective debridement of epithelium and protection of adjacent and underlying
      stroma with moderate viscosity solutions enhances the surgeons's ability to
      obtain a smooth and clear surface while minimizing corneal thinning. Even with
      these strategies and use of plano disc ablation, net hyperopic shift generally
      occurs with broad large area therapeutic ablation. CONCLUSIONS: Superficial
      corneal opacities and irregularities can be surgically treated with the excimer
      laser as an alternative to the more invasive procedure of lamellar keratoplasty.
      Treatment failures can then go on to lamellar keratoplasty while successfully
      treated patients are more rapidly rehabilitated at lower total cost than a
      lamellar graft. Refinement of treatment strategies to minimize the hyperopic
      shift and facilitate masking around irregularities will further improve the
      results.

PMID- 1390416
TI  - Avoid both radial keratotomy with small optical zones and hexagonal keratotomy.

PMID- 1390417
TI  - [ATL and its virus].
AB  - A retrovirus called Human T cell leukemia virus type 1 (HTLV-1) is a causative
      agent of adult T cell leukemia (ATL). A cultured cell line called MT-2, produces
      constitutively HTLV-1. The characteristics of HTLV-1 produced from MT-2 has been
      extensively investigated. The molecular mechanism of ATL leukemogenesis by HTLV-1
      is discussed.

PMID- 1390418
TI  - [AIDS and its virus].
AB  - An etiological agent of AIDS is a human retrovirus called HIV. The genomic
      structure of HIV features regulatory genes in which tat and rev genes control the
      viral replication and affect cellular functions. Understanding their molecular
      mechanism may provide a clue to prevent the onset of AIDS from the viral carriers
      and to direct drug designing of AIDS.

PMID- 1390419
TI  - [Establishment and characterization of a human colonic cancer cell line
      expressing carbohydrate antigen 19-9 and carcinoembryonic antigen].
AB  - Colonic cancer cell strain KE43 was established from a human colonic cancer
      diagnosed histologically as a predominantly well differentiated adenocarcinoma
      with minute foci of poorly differentiated adenocarcinoma. The well differentiated
      adenocarcinoma cell line was identified as the major morphological picture in
      xenografts of KE43 and 58 in nude mice, but this changed to poorly differentiated
      adenocarcinoma in passage 105. Doubling time of this cancer cell line was 22.5
      hours in passage 105. The modal numbers of chromosomes were 41 and 76. Cancer
      cells could be heterotransplanted in 100% of the nude mice. The tumor cells
      produced and secreted CA19-9, CEA and Laminin into the spent medium. This cell
      line appears to provide a useful system for studying colonic cancer in vivo and
      in vitro.

PMID- 1390420
TI  - [PCR-SSCP--rapid and easy detection of DNA-sequence changes].
AB  - PCR-SSCP analysis is a rapid, simple and sensitive technique for detection of
      various mutations, including single nucleotide substitutions, insertions and
      deletions, in PCR-amplified DNA fragments. Here I review, the principle and
      sensitivity of the technique, and also show how this technique has been used in
      clinical and basic medical sciences.

PMID- 1390421
TI  - Establishment of leukemia cell lines, BALM-6, BALM-7 and BALM-8 with B-cell
      characteristics from a patient with acute lymphoblastic leukemia.
AB  - Three leukemia cell lines, BALM-6, -7 and -8 were established from the bone
      marrow of a patient with acute lymphoblastic leukemia. Based on immunophenotypic
      and the cytogenetic analysis and on the expression of immunoglobulins on both the
      cell surface and in the cytoplasm, BALM-6, BALM-7 and BALM-8 are clonal leukemic
      cell populations of B cell origin.

PMID- 1390422
TI  - Stimulation of orbital growth by the use of expandable implants in the
      anophthalmic cat orbit.
AB  - We evaluated the efficacy of expandable orbital implants to stimulate bone growth
      in the anophthalmic cat orbit. Eighteen cats unilaterally enucleated at 2 weeks
      of age received either expandable orbital implants (groups A1 and A2), solid
      silicone sphere implants of 12 mm or 8 mm (groups B1 and B2), or no implant
      (group C). Those cats with expandable implants (group A) had the implant size
      increased by 0.5 ml injections of saline at 2-week intervals starting at 8 weeks
      of age until a final volume of 4 cc was reached. Four of the expandable implants
      were found to be only partially inflated at 20 weeks and were subgrouped A2. At
      20 weeks of age, the anophthalmic orbits with fully inflated expanders showed no
      significant difference in either orbital volume or orbital entrance area when
      compared with control orbits: volume (91.2%), area (95.7%) (p = 0.01). These same
      orbits also showed a significant increase in both orbital volume and orbital
      entrance area when compared with the growth obtained by any other group. These
      other groups showed growth, expressed as a percentage of normal growth, as
      follows: partially inflated implant: volume (63.0%), area (69.0%); 12-mm sphere
      implant: volume (57.0%), area (54.5%); 8-mm sphere implant: volume (46.5%), area
      (44.6%); no implant: volume (47.6%), area (43.6%) (p = 0.01). This study suggests
      that the use of expandable orbital implants stimulates bony growth in the
      immature cat orbit. Bony stimulation was proportional to volume implanted, and
      expandable orbital implants achieved maximum bony stimulation in the groups
      studied.

PMID- 1390423
TI  - Lower eyelid retraction following blepharoplasty.
AB  - Thirty consecutive patients with lower eyelid retraction after blepharoplasty
      were treated surgically with varying degrees of success. Successful outcome
      depended on various anatomic and pathologic factors, including the time elapsed
      since blepharoplasty, the prominence of the globe and its effect on eyelid
      contour, and the degree of septal or skin involvement. Satisfactory results were
      also dependent on surgical techniques used. We discuss several surgical
      techniques and offer advice concerning the selection of a surgical procedure in
      light of various pathologic parameters.

PMID- 1390425
TI  - Treatment of the paradoxic inversion of the lashes in ectropion.
AB  - Ectropion leads to chronic inflammation of the exposed conjunctiva. This
      inflammation can lead to shrinkage and to a cicatricial paradoxic inversion of
      the lashes. When the lid margin is surgically brought into its correct position,
      these lashes may become trichiatic. The surgical eversion of the lid margin at
      the time of the ectropion operation can prevent this complication.

PMID- 1390424
TI  - Angle closure glaucoma following a combined blepharoplasty and ectropion repair.
AB  - This paper reports an occurrence of angle closure glaucoma following a combined
      blepharoplasty and ectropion repair. We are unaware of any previous reports of
      such an incident. Specific to this case was the coexistence of a cataract that
      contributed to the narrowing of the anterior chamber. This condition, along with
      pupil dilation secondary to the anesthetic, precipitated a phacomorphic angle
      closure glaucoma attack, necessitating emergency cataract surgery. Because other
      procedures involve pupillary dilation as a potential side effect, we recommend an
      increased awareness of this potential postoperative complication.

PMID- 1390426
TI  - Eyelid reconstruction with hard palate mucosa grafts.
AB  - Hard palate mucosa grafts are an excellent replacement for tarsus and conjunctiva
      in eyelid reconstruction. Twenty-five eyelids from 18 patients underwent eyelid
      reconstruction using hard palate mucosa grafts. Patients were treated for a
      variety of disorders including postblepharoplasty lower eyelid retraction,
      cicatricial entropion, eyelid retraction secondary to thyroid eye disease, and
      lagophthalmos following surgery for paralytic ptosis. Surgical results were
      evaluated, grafts were measured for postoperative shrinkage, and donor site
      healing was recorded. Several patients had hard palate biopsy specimens
      evaluated. One of these patients also had a graft biopsied after it had been in
      place for 3 months. A review of hard palate anatomy and histology and a
      discussion of surgical technique are presented.

PMID- 1390428
TI  - Lacrimal mechanics in the enucleated state.
AB  - Our understanding of tear-flow mechanics is based upon work performed on eyes in
      the normal, nucleated state. On this basis, decisions are made regarding the
      reconstruction of lacerated canaliculi. When called upon to repair such a
      laceration in a patient who is coincidentally undergoing a traumatic enucleation,
      the surgeon has traditionally done so when it was practical. This assumes that
      the tear-flow requirements in these patients are similar to those of patients in
      the nucleated condition. We have investigated twelve patients after traumatic
      enucleation and believe, based on this preliminary work, that eyes in the
      enucleated state may not have the same tear-flow requirements and therefore may
      not require canalicular reconstruction.

PMID- 1390427
TI  - Eyelid reanimation for the treatment of paralytic lagophthalmos: historical
      perspectives and current applications of the gold weight implant.
AB  - Gold weight implants have been used for over 30 years in the setting of eyelid
      rehabilitation following facial nerve paralysis; however, there has been a
      renewed interest by ophthalmologists in this reanimation technique in recent
      years. This article reviews the history of gold weight eyelid implantation and
      presents the results of gold weight eyelid implantation over a 15-month period in
      23 patients. A 92% success rate was obtained (average follow-up, 12 months).
      Surgical technique and indications are discussed along with postoperative
      complications.

PMID- 1390429
TI  - Postcataract surgery endophthalmitis in a patient with a functioning Jones tube.
AB  - Dacryocystorhinostomy with Jones tube placement has proven to be an effective
      method for correcting upper-system lacrimal drainage obstruction. The present
      case report illustrates the potential risk of bacterial contamination of the
      operative field during subsequent cataract surgery by retrograde passage of
      airway secretions. Temporary occlusion of the Jones tube by a silicone plug can
      eliminate this potential source of endophthalmitis. In addition, temporary
      occlusion of the Jones tube in the office can be used to determine the
      effectiveness of lacrimal drainage through a reconstructed canalicular system.

PMID- 1390430
TI  - Eyebrow analysis after blepharoplasty in patients with brow ptosis.
AB  - Fifteen patients and 28 eyes with measurable eyebrow ptosis underwent standard
      upper eyelid blepharoplasty with or without sub-brow fat excision. The patients
      were educated about the status of their eyebrow position and the effects of
      either direct or indirect methods of brow elevation. The patients either refused
      or chose not to undergo browpexy by any method. Eleven patients and 22 eyes
      showed an insignificant change in their eyebrow position after surgery. Two
      patients and three eyes had a mild to moderate descent of the eyebrow and two
      patients had what was felt to be significant worsening of their eyebrow ptosis in
      one or both eyes. However, all were pleased with their result. Information as
      such, after a careful review of the literature, has not previously been
      published.

PMID- 1390431
TI  - Atypical magnetic resonance findings in an orbitofrontal cholesterol granuloma.
AB  - Cholesterol granuloma of the orbit is an uncommon entity, although it frequently
      occurs in the middle ear and petrous apex. It is isodense with brain on computed
      tomographic scanning and cannot always be differentiated from more serious
      conditions. Magnetic resonance imaging (MRI) has facilitated the preoperative
      diagnosis of cholesterol granuloma outside of the orbit because of high signal
      characteristics on T1- and T2-weighted images. These findings have been
      considered nearly pathognomonic, but they have previously been described in only
      one patient with orbitofrontal involvement. We present a case of orbitofrontal
      cholesterol granuloma with uncharacteristic signal intensities on magnetic
      resonance imaging.

PMID- 1390432
TI  - The CT and MRI features of an unusual case of isolated orbital neurofibroma.
AB  - A 35-year-old woman developed painful proptosis of the left eye over a period of
      3 weeks. Orbital computed tomography and magnetic resonance imaging revealed a
      well-circumscribed superior orbital tumor with variable density. The mass was
      removed entirely by way of a superior orbitotomy. Histopathologically, it was
      found to be a neurofibroma. The patient had no clinical findings of
      neurofibromatosis. The presence of extensive myxomatous degeneration and the
      dense collection of collagen bundles in the tumor are correlated with the unusual
      computed tomography and magnetic resonance imaging features.

PMID- 1390433
TI  - Homing of blood, splenic, and lung emigrant lymphoblasts: comparison with the
      behaviour of lymphocytes from these sources.
AB  - The distinctive homing patterns of [125I]deoxyuridine-labelled lymphoblasts and
      51Cr-labelled lymphocytes from the three sites--splenic and pulmonary venous
      emigrants, and peripheral blood--were demonstrated by study of their entry into a
      large number of tissues. These included the major organs such as the lung, liver,
      bone marrow, spleen, skin, and muscle, and several lymph nodes (LNs), Peyer's
      patches (PPs), tonsils and thymus, portions throughout the gastrointestinal tract
      and immunologically-stimulated sites. Major differences in homing of blood blasts
      (up to 4-fold) were found in particular tissue types, such as the different LNs,
      three PP types, and the three tonsils, and their distribution was quite different
      from lymphocytes. While splenic blasts behaved like blood blasts, lung blasts
      showed even more distinctive homing, e.g. to tissues with particular blast
      uptake, including spleen, stomach, bladder, portal and stimulated LNs, and liver
      and lung. While blast recovery data showed that all types homed well to bone
      marrow (about 25%) and the gastrointestinal wall (about 15%), the roughly 50%
      found in blood, muscle, skin, lung, and liver showed some homing preferences:
      blood blasts tended to stay more in blood, splenic blasts to home to muscle, and
      lung blasts to liver and lung. These studies have demonstrated that
      physiologically-derived lymphoblasts are not predominantly mucosal-homing but
      distribute through several non-lymphoid organs and that, even considering only
      those in the blood compartments, they show differences in homing preference.

PMID- 1390434
TI  - Five novel antigens illustrate shared phenotype between mouse thymic stromal
      cells, thymocytes, and peripheral lymphocytes.
AB  - Previously we characterized by immunohistology a group of rat anti-mouse thymic
      stromal mAbs (MTS 12, 32, 33, 35, and 37), which recognized novel plasma membrane
      determinants on both thymic stromal cells (TSCs) and thymocytes. The present
      study investigates in more detail this incidence of shared phenotype by an
      extensive flow cytometric analysis of MTS mAb reactivity on TSCs, thymocyte
      subsets, peripheral lymphocytes, and bone marrow cells. Examination of freshly
      isolated or cultured heterogeneous TSCs and TSC clones confirmed that the mAb
      identified plasma membrane molecules on distinct subsets of these cells. All but
      MTS 12 reacted with epithelial cells. Triple-labelling illustrated that MTS 32,
      33, and 37 were also reactive with more than 90% of total thymocytes, but varied
      in their distribution on the four major CD4 and CD8 defined subsets. MTS 12,
      staining with thymic vascular endothelium by immunohistology, labelled more than
      95% of each subset. MTS 35 reactivity in each subset correlated strongly with
      only the immature populations. Examination of peripheral lymphocytes by triple-
      and double-labelling unexpectedly showed that MTS 33, 35, and 37 did not
      recognize peripheral T cells but labelled all B cells. MTS 32 was negative for B
      cells, but positive for all CD8+ T cells, yet only a subset of CD4+ T cells.
      Further, MTS 33, 35, and 37 were present on a significant percentage of bone
      marrow cells. MTS 12 reacted with virtually all peripheral T and B cells, and
      about 50% bone marrow leukocytes. Collectively these results reveal the same
      novel epitopes on different thymic cell types and subsets thereof, highlighting
      specific similarities between cells of apparently diverse lineages. These
      findings may be of importance in the delineation of intercellular communications
      within the thymus and emphasize the integrated nature of the microenvironment in
      this organ.

PMID- 1390435
TI  - Characterization of murine CD10, an endopeptidase expressed on bone marrow
      adherent cells.
AB  - The CD10/neutral endopeptidase (NEP) gene was identified in murine genomic DNA
      using a human CD10 cDNA probe. It is transcribed most abundantly in kidneys
      resulting in RNA transcripts of 3.4, 6.0, and 6.2 kb. The activity of the murine
      CD10/NEP shows identical kinetic parameters, Km and Ki, to those observed for
      this enzyme in other species. Two mAbs raised against rabbit NEP detect a 100 kDa
      protein by Western blot analysis; the antigen immunoprecipitated from extracts of
      lung shows specific NEP activity. CD10/NEP, as analyzed by Western blot and
      enzymatic activity, is expressed at high levels in kidney and lung, and at lower
      levels in liver, brain, thymus, spleen, and bone marrow. Analysis of bone marrow
      subpopulations indicate that the majority of CD10/NEP is associated with cells
      adherent to plastic and with subpopulations that do not express the surface
      markers AA4.1, B220, Mac-1, and Gr-1. These results suggest that CD10 is
      primarily associated with the stromal elements in murine bone marrow. A bone
      marrow stromal line, BMS 2.2, also expresses high levels of CD10/NEP. This
      peptidase activity on the surface of stromal cells may influence lymphopoiesis or
      other hematopoietic processes through the hydrolysis of regulatory peptides in
      the microenvironment.

PMID- 1390437
TI  - Thymocytes can tolerize thymocytes by clonal deletion in vitro.
AB  - Clonal deletion of thymocytes bearing TCR for self antigens is one major
      mechanism of T cell tolerance induction. Peptide antigen-induced deletion of
      thymocytes from alpha beta TCR transgenic mice has been studied using single cell
      suspension cultures. The results show that antigen-presenting immature CD4+CD8+
      thymocytes can tolerize antigen-reactive immature thymocytes in vitro by
      programmed cell death (apoptosis) 6-8 h after antigen exposure. Antigen-induced
      apoptosis of immature thymocytes was inhibited by antibodies specific for the
      alpha beta TCR, CD3, CD8, and LFA-1 molecules. This implies that clonal
      elimination of self-reactive CD4+CD8+ thymocytes does not depend on specialized
      deleting cell types in the thymus and occurs whenever the TCR of immature
      thymocytes bind antigen fragments presented by MHC molecules.

PMID- 1390436
TI  - MHC and malaria: the relationship between HLA class II alleles and immune
      responses to Plasmodium falciparum.
AB  - In mice, immune responses to subunits of defined malaria antigens are regulated
      by genes mapping within the MHC and it has been suggested that such genetic
      restriction will be a major obstacle in the development of a human malaria
      vaccine. The relationship between class II human leukocyte antigen (HLA) genes
      and immune recognition of three candidate antigens for a vaccine against
      Plasmodium falciparum malaria has been investigated in a human population living
      in a malaria endemic area of West Africa. The study population was shown to be
      extremely heterogeneous for HLA class II alleles and marked differences in
      allelic frequency were detected between members of different ethnic groups. One
      class II DQA-DQB combination (serological specificity DQw2) was particularly
      common among members of the Fula ethnic group. This haplotype was significantly
      associated with higher than average levels of antibody to a peptide epitope,
      (EENV)6, of the malaria antigen Pf155/RESA. There was little evidence of
      association between HLA class II genotype and cellular proliferative or
      interferon gamma responses to the antigens tested. Overall, the number of
      significant associations between immune responses and specific HLA class II
      haplotypes was greater than would be expected by chance but less than would be
      expected if class II-dependent genetic restriction were a major factor governing
      human immune responses to malaria antigens. Thus, although some qualitative
      variation in the immune response to vaccine antigens may occur in ethnically
      different target populations, widespread HLA-associated nonresponsiveness to a
      multivalent subunit malaria vaccine is unlikely.

PMID- 1390438
TI  - Effects of the lpr/lpr mutation on T and B cell populations in the lamina propria
      of the small intestine, a mucosal effector site.
AB  - MRL mice, which develop a lymphoproliferative disease characterized by increased
      numbers of alpha/beta T cell receptor+ (TCR+) B220/6B2+CD4-CD8- T cells
      [lymphoproliferation (lpr) T cells], were studied for the effect of the lpr/lpr
      mutation on the mucosal immune system in the gastrointestinal (GI) tract. We
      analyzed the effect of the lpr gene mutation on T and B cell populations in the
      Peyer's patches (PP) and the lamina propria lymphocytes (LPLs), as examples of
      major IgA inductive and effector tissues in the GI tract respectively. Normal
      mouse PP contain B cells committed to IgA (surface IgA+) but only low numbers of
      B cells producing IgA. However, enhanced spontaneous IgA and IgG synthesis occurs
      in the PP of MRL mice. Further, we have now shown that PP of MRL mice are
      populated by lpr T cells. Interestingly, lpr T cells were not present in
      significant numbers in LPLs of MRL mice, even in older animals. Of interest was
      the finding that the ratio of CD4+ to CD8+ T cells in the lamina propria was
      lower in MRL when compared with control mice, and the CD8+ T cell subset actually
      predominates in LPLs of autoimmune mice. In addition, the number of gamma/delta
      TCR+ T cells in LPL of MRL lpr/lpr mice was significantly increased, especially
      in MRL lpr/lpr mice at 6 and 12 weeks of age. When the isotype distribution of B
      cells in LPLs was analyzed, no changes were noted in MRL lpr/lpr mice in
      comparison with MRL +/+ or normal control mice, and the pattern was IgA much
      greater than IgM greater than IgG. These results show that although increased
      numbers of CD8+ T cells and gamma/delta TCR+ cells occur in the LPLs of MRL mice,
      a normal distribution of plasma cell isotypes (IgA much greater than IgM greater
      than IgG) is found in this mucosal compartment. Further, Ipr T cells do not
      develop in the lamina propria compartment of the GI tract.

PMID- 1390439
TI  - A self-reactive T cell population that is not subject to negative selection.
AB  - In male mice expressing a transgenic alpha beta TCR which recognizes a male
      antigen (HY), T cells which do not express normal levels of CD8 escape thymic
      deletion and appear in the periphery. These consist of two distinct populations,
      one which lacks expression of both CD4 and CD8, and one with low levels of CD8.
      Neither population has anti-HY reactivity, consistent with the known requirement
      of this TCR for CD8. We now describe the consequences of expression of both the
      anti-HY TCR transgene and a constitutive CD8.1 transgene on T cells of male mice.
      Peripheral T cells in these male 'double transgenic' mice express both the anti
      HY TCR and normal levels of CD8, and can proliferate to male antigen in vitro.
      These cells do not express the endogenous allele of CD8 (CD8.2), suggesting that
      the increase in CD8 levels due to the CD8.1 transgene leads to the deletion of
      the CD8.2low population. In contrast, the CD8.1 transgene does not lead to the
      deletion of the CD8.2- population. This implies that, unlike the majority of
      alpha beta T cells, TCR+CD4-CD8- cells in TCR transgenic mice are not subject to
      deletion.

PMID- 1390440
TI  - Transforming growth factor-beta 1 enhances IgG and IgA sheep red blood cell
      responses.
AB  - Antibody responses to ingested antigens can be inhibited by a mechanism known as
      oral tolerance which acts to prevent excessive stimulation from luminal contents.
      Local IgA responses can be induced in this non-responsive environment and during
      intestinal inflammation, mucosal IgG responses can also be increased. The purpose
      of this study was to compare a panel of cytokines to factors from macrophage-T
      cell co-culture supernatants for their ability to enhance isotype and sheep red
      blood cell (SRBC)-specific plaque-forming cell responses in an in vitro model of
      oral tolerance. IL-2, IL-4, IL-5, and IL-6, which have been implicated in IgA
      regulation of lipopolysaccharide-stimulated B cells, were not capable of
      enhancing responses in tolerized cultures; however, transforming growth factor
      (TGF)-beta 1 had a dose-dependent ability to enhance responses to the T cell
      dependent antigen SRBCs in this system. The enhancement was only seen when
      antigen was present and was neutralized by specific rabbit antiserum but not
      normal rabbit IgG. Similar treatment of soluble factors from the macrophage-T
      cell co-cultures did not inhibit their ability to enhance responses suggesting at
      least two distinct molecular mechanisms could augment responses in tolerized
      cultures. This was substantiated further by showing that TGF-beta 1 was not
      isotype-specific. In contrast, adsorption of the macrophage-T cell co-culture
      supernatants against monoclonal IgA or IgG removed isotype-specific binding
      factors which were necessary for the enhancement of IgA and IgG
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390441
TI  - 'Natural' T cells responsive to malaria: evidence implicating immunological cross
      reactivity in the maintenance of TCR alpha beta+ malaria-specific responses from
      non-exposed donors.
AB  - It is now generally accepted that peripheral blood of humans not exposed
      previously to malaria contains T cells which proliferate vigorously in response
      to malaria parasites and antigens. Although it has been claimed that these cells
      express a memory phenotype, their origin is uncertain. We have examined the
      phenotype and immunological responses of such cells. We confirm that these cells
      do express the 'memory phenotype', CD45Ro, in that depletion of such cells, but
      not of CD45Ra (virgin) cells, abrogates the immune response to malaria parasites.
      In an effort to define the genesis of these responses, numerous malaria-specific
      T cell clones have been generated from non-exposed individuals. These were tested
      for reactivity to a large panel of common bacterial, viral, and fungal pathogenic
      and non-pathogenic organisms. Most clones proliferated vigorously in response to
      one or more such organisms, while many clones demonstrated smaller but
      significant degrees of proliferation in response to many different organisms. Our
      data offers insights into the maintenance of immunological memory. All clones
      examined were CD3+, CD4+, CD8-, TCR alpha beta+, and TCR delta-. The ratio of TCR
      alpha beta+ to TCR delta+ cells among peripheral blood lymphocytes increased
      during polyclonal culture in the presence of parasite. The high frequency of such
      cells in peripheral blood (1/800-1/9000), and their response to a wide range of
      geographically different Plasmodium falciparum isolates and clones by both
      proliferation and lymphokine secretion (predominantly IFN-gamma) with a high
      degree of sensitivity (less than 1 parasite/microliters blood in some cases)
      suggests that these cells must be quickly activated following malaria infection.
      Their contribution to the outcome of the disease (protection/immunopathology) may
      be significant.

PMID- 1390442
TI  - Extensive CD4 cross-linking inhibits T cell activation by anti-receptor antibody
      but not by antigen.
AB  - Anti-CD4 mAbs have been shown to inhibit T cell activation in a variety of ways.
      We have tested a panel of IgG and IgM anti-CD4 mAbs for their effects on the
      activation of a cloned T cell line by antigen presented by syngeneic accessory
      cells, by soluble anti-T cell receptor antibodies, and by mitogenic lectins. Both
      IgM and IgG mAbs to CD4 inhibit responses to mitogenic lectins. However, IgM, but
      not IgG, anti-CD4 antibodies inhibit T cell activation by mAbs specific for the
      TCR. This inhibitory activity appears to be due to the signaling effects of IgM
      mAbs, as cross-linked IgG antibodies mimic the behavior of the IgM anti-CD4
      antibodies. Inhibition of T cell activation correlates with the ability of IgM
      and of cross-linked IgG anti-CD4 antibodies to induce tyrosine phosphorylation of
      the CD4-associated tyrosine kinase p56lck and an unknown substrate, pp32.
      Surprisingly, we find that the IgM anti-CD4 mAbs tested had no effect on the
      specific antigen recognition, despite their potent inhibitory effects on the
      other responses of the same cloned T cell line. These results suggest that
      multivalent CD4 interactions with ligands such as MHC class II molecules are
      inhibitory of T cell activation, but that this inhibition can be reversed when
      CD4 and the TCR bind the same ligand. We discuss the possible implications for
      positive intrathymic selection of these findings on signaling through CD4.

PMID- 1390443
TI  - Substituent distribution on O,N-carboxymethylchitosans by 1H and 13C n.m.r.
AB  - The use of the n.m.r. method in the investigation of chitosan carboxymethylation
      was evaluated. It seems to be the most effective technique to determine
      concurrently the degree and the position of substitution of the carboxymethylated
      chitosan derivatives. The 13C-n.m.r., by the DEPT method, 1H-1H and 1H-13C-n.m.r.
      correlations give much valuable information from the chemical shifts of the
      complex carboxymethylchitosan spectra. The relative reactivity of the functional
      groups of chitosan towards carboxymethylation was also determined assuming a
      higher reactivity of the C-6 position.

PMID- 1390445
TI  - Patterson methods in fibre diffraction analysis.
AB  - The potential of the Patterson methods for X-ray diffraction studies of textures
      is examined in DNA fibres. Patterson analysis, which is rarely used in these
      situations, is shown to yield important information on the preliminary
      interpretation of diffraction patterns and to increase the reliability of the
      three-dimensional structural pattern obtained for polymeric molecules. We also
      show how the screw symmetry of helical molecules can be used to calculate their
      electron density by means of the three-dimensional Patterson function.

PMID- 1390444
TI  - Effect of chemical modifications on the susceptibility of collagen to
      proteolysis. II. Dehydrothermal crosslinking.
AB  - Collagen was dehydrothermally treated (heat cured) by heating dry under vacuum at
      60, 80, 100 and 120 degrees C. The change in stability was determined by
      subjecting to measurement of gross crosslinking, content of lysino-alanine and
      naturally occurring collagen crosslinks, shrinkage temperature (TM),
      susceptibility to digestion by lysosomal thiol proteases, and susceptibility to
      pepsin and trypsin. Morphological changes were examined by electron microscopy.
      The in vivo biodegradation of dehydrothermally treated collagen sponges was
      investigated using a rat lumbar muscle implantation model for up to 28 days. For
      all heat-cured collagens, the data strongly indicated that both crosslinking and
      denaturation/degradation was present in increasing quantities with increasing
      temperature of treatment, its level was too low (maximum 179 pmol mg-1) to
      account for the decreased solubility and increased molecular weight gross changes
      observed. Increasing resistance of treated collagen to both lysosomal cathepsins
      and pepsin correlated well with increased crosslinking and increasing temperature
      of the heat-curing process. However, increased denaturation/degradation of the
      collagen at higher temperatures was revealed by electrophoretic analysis, trypsin
      hydrolysis data and by electron microscopy. Differential scanning calorimetry
      (d.s.c.) correlated well with these results showing an increased level of
      denaturation in heated samples. The in vivo study showed little difference
      between control and heat-cured samples except for the material treated at 120
      degrees C which was biodegraded in vivo at a significantly faster rate. The data
      shows, therefore, that crosslinking induced by the dehydrothermal treatment of
      collagen decreases its rate of proteolysis at acid pH in vitro. However, the
      simultaneous denaturation/degradation of the protein during the heat-cure process
      appears to be a more important factor in determining the fate of the material
      implanted into rat muscle.

PMID- 1390446
TI  - Comparative structural analysis of desmoplakin, bullous pemphigoid antigen and
      plectin: members of a new gene family involved in organization of intermediate
      filaments.
AB  - Desmoplakins (DP) and bullous pemphigoid antigen (BPA) are major plaque
      components of the desmosome and hemidesmosome, respectively. These cell adhesion
      structures are both associated intimately with the intermediate filament (IF)
      network. Structural analyses of DP and BPA sequences have indicated that these
      molecules are likely to form extended dumbbell-shaped dimers with a central rod
      and globular end domains. Recent sequence data have indicated that the N-terminal
      domains of both DP and BPA (like their C-terminal domains) are highly related:
      the former contain regions of heptad repeats that are predicted to form several
      alpha-helical bundles. Comparisons of DP and BPA protein sequences with that of
      plectin (PL), a 466 kDa IF-associated protein, have also revealed large scale
      homology. Identities between their N-terminal domains are: DP:BPA = 35%, DP:PL =
      32%, BPA:PL = 40%, suggesting that BPA is more closely related to PL than DP in
      this region. In the C-terminal domains, which contain a 38-residue repeating
      motif, however, DP and PL are closer relatives (identities: DP:BPA = 38%, BPA:PL
      = 40%, DP:PL = 49%). The central domains of all three proteins have extensive
      heptad repeat substructure, express the same periodic distribution of charged
      residues, and are predicted to form two-stranded alpha-helical coiled-coil ropes.
      These observations suggest that DP, BPA and PL belong to a new gene family
      encoding proteins involved in IF organization.

PMID- 1390447
TI  - Molecular mechanical study of the stability of the Lys-Ala-Ala tripeptide dimer.
AB  - A molecular mechanical study of two Lys-Ala-Ala tripeptide chains in interaction
      is presented. The study was carried out to explore the feasibility of dimer
      formation and explain some features of the crystal structure not completely
      understood. The role of the counterions present in the crystal structure on the
      conformation has been included in this study by investigating the effect of
      removing the charges on the lysyl side chains. The results of the present
      molecular mechanical study explains well the structural features found by X-ray
      crystallography, complementing that study.

PMID- 1390448
TI  - B-Z conformational transition and hydration of poly (dC-dG).poly (dC-dG) in
      fibres.
AB  - The B-Z transition of poly(dC-dG).poly(dC-dG) has been studied by fibre X-ray
      diffraction and measurement of fibre dimensions. The polymorphism of the Z form
      is well observed as a function of variations of the r.h. (relative humidity). The
      Z to B transition is obtained at very high r.h. values. The cooperative
      transition from B to Z is associated with a disorganization of the fibre. Details
      about the hydration of the polynucleotide during conformational transitions are
      presented and it is shown that a nucleotide in Z form can be associated with up
      to 16 water molecules and up to 22 when in the B form.

PMID- 1390449
TI  - Improved method for i.r. determination of the degree of N-acetylation of
      chitosan.
AB  - Three published i.r. absorption band ratios for determining the % N-acetylation
      of chitosan have been used to follow the rate of alkaline deacetylation of
      chitin. Only one, the A1655/A3450 ratio, gives the expected rate of deacetylation
      curve. Consideration of the various i.r. ratios has led to a new relationship, %
      N-acetylation = (A1655/A3450) x 115, where the absorbance of the amide I band at
      approximately 1655 cm-1 is determined using the baseline proposed previously. The
      values obtained using this proposed relationship agree closely with those
      obtained from dye adsorption measurements for chitosans having % N-acetylation
      values in the range 0-55%.

PMID- 1390451
TI  - On molecular packing in pN-collagen sheets.

PMID- 1390450
TI  - Helicoidal self-ordering of cellulose microfibrils in aqueous suspension.
AB  - In many skeletal support systems of plants and animals, cellulose, chitin, and
      collagen occur in the form of microfibrils ordered in a chiral nematic fashion
      (helicoids). However, these structures remain poorly understood due to the many
      constituents present in biological tissues. Here we report an in vitro system
      that attracts by its simplicity. Only one chemical component, cellulose, is
      present in the form of fibrillar fragments dispersed in water. Above a critical
      concentration the colloidal dispersion separates spontaneously into a chiral
      nematic liquid crystalline phase. On drying this phase solidifies into regularly
      twisted fibrillar layers that mimic the structural organization of helicoids in
      nature.

PMID- 1390452
TI  - Quantifying anti-inflammatory agents' potency by measurement of response to
      dinitrochlorobenzene challenge.
AB  - Classical assays of topical corticosteroid potency based on the induction of
      vasoconstriction are unsatisfactory for a number of reasons. These include the
      doubtful relevance of vasoconstriction to immune inflammation, and more
      importantly, the inability to compare non-steroidal agents with corticosteroids.
      Here we describe a simple assay in which the inhibitory effect of agents upon
      delayed type hypersensitivity response to dinitrochlorobenzene can be quantified
      by measurements of reaction as skinfold thickness with Harpenden callipers. Using
      this system we have confirmed the greater potency of clobetasol propionate
      (Dermovate) compared with betamethasone valerate (Betnovate), but the evidence
      for an inhibitory effect of topical cyclosporin (10% cream) compared with base on
      this response is less convincing.

PMID- 1390453
TI  - Determination of the action spectrum for UV-induced plasminogen activator
      synthesis in mouse keratinocytes in vitro.
AB  - Mouse epidermal keratinocyte-derived Pam 212 cells were irradiated with UV light,
      and the culture media were examined for plasminogen activator (PA) activity by
      measuring the capacity to convert exogenous plasminogen into plasmin. Exposure of
      cells to a broad spectrum of light in the UVB range induced a significant
      elevation of PA activity at 16 h after irradiation. A dose-response study
      revealed that a maximal enhancement, 15-fold higher than non-irradiated controls,
      was induced at a sublethal UVB dose of 100 J/m2, which significantly inhibited
      cell proliferation without affecting cell viability. Addition of 5 micrograms/ml
      of cycloheximide lowered the UV-induced elevation of PA activity, suggesting that
      protein synthesis is required for this phenomenon. Action spectra for PA
      synthesis were obtained by irradiating cells with monochromatic light ranging
      from 250 to 360 mm, and the data demonstrated that the action spectrum was 250
      320 nm in length with a peak between 260 and 280 nm. The results suggest that UV
      exposure is an important physiological trigger for modulating PA synthesis in the
      epidermis.

PMID- 1390454
TI  - Anti-proliferative effects of protein kinase C inhibitors in human keratinocytes.
AB  - Various lines of evidence indicate that protein kinase C, a key enzyme in
      transmembraneous signal transduction, is involved in the regulation of
      keratinocyte proliferation. In the present study we have investigated the effects
      of various structurally unrelated protein kinase C inhibitors on the
      proliferation of HaCa T cells, a non-tumorigenic human keratinocyte cell line.
      All protein kinase C inhibitors dose-dependently inhibited cell proliferation as
      assessed by the incorporation of radioactively labelled thymidine and amino acids
      as well as the increase in total protein content in keratinocytes. The potencies
      of the drugs to inhibit cell proliferation were strongly correlated to their
      inhibitory potency on purified protein kinase C, displaying a correlation
      coefficient of 0.97. Methotrexate, an anti-proliferative drug, was found not to
      inhibit protein kinase C. Therefore, our data provide evidence that protein
      kinase C is crucially involved in the regulation of keratinocyte proliferation
      but is not the only target of anti-proliferative drug action.

PMID- 1390455
TI  - Production and characterization of monoclonal antibodies to Treponema pallidum.
AB  - This study was attempted to produce the monoclonal antibodies specific for
      Treponema pallidum and to investigate their characteristics, thereby contributing
      to identify the antigenic structure and to apply the diagnosis of syphilis. The
      seven clones (YS 3, YS 75, YS 307, YS 481, YS 343, YS 1 and YS 406) secreting
      monoclonal antibodies reactive with T. pallidum were produced. The isotypes of
      the seven monoclonal antibodies produced were defined. Optical densities of the 7
      monoclonal antibodies were ranged from 0.59 to 1.48 as measured by ELISA.
      Monoclonal antibodies from 5 of the 7 clones which could agglutinate sheep RBC
      sensitized with T. pallidum, showed strong fluorescences. The monoclonal antibody
      from YS 343 was cross-reactive with non-pathogenic treponemes, but the other 6
      monoclonal antibodies reacted with T. pallidum specifically. On immunoblotting,
      monoclonal antibodies from 5 of the 7 clones reacted with a polypeptide of a
      molecular weight of 47 kDa, and monoclonal antibodies from YS 343 reacted with a
      polypeptide of 64 kDa common to both T. pallidum and T. phagedenis. The above
      results revealed that 7 clones secreting monoclonal antibodies reactive to T.
      pallidum were produced successfully, and specific antibodies reacting with major
      antigenic polypeptides of a molecular weight of 47 kDa would be useful in the
      diagnosis of syphilis in the future.

PMID- 1390456
TI  - Cholinergic sensitivity of the eccrine sweat gland in trained and untrained men.
AB  - The purpose of this study was to compare the cholinergic responsiveness of the
      human sweat gland in trained and untrained men. Eighteen healthy male volunteers
      (9 trained, 9 sedentary) served as subjects. Pilocarpine concentration vs. sweat
      rate dose-response curves were obtained from each subject using iontophoresis.
      From these measurements, maximal iontophoretic sweat rate (SRmax) was determined
      and correlated with each subject's maximal oxygen uptake (VO2max). The trained
      group had a significantly (P less than 0.05) greater mean SR max and their mean
      dose-response curve was shifted up and to the left, as compared to the sedentary
      controls. Furthermore, VO2max was significantly correlated with SRmax (r = 0.76).
      These findings suggest that the modification occurring in the human sweat gland
      after training may include improvements in both SRmax and cholinergic
      sensitivity, and support the hypothesis that the potentiation in sweating
      following training is achieved via a peripheral mechanism.

PMID- 1390457
TI  - Production of experimental staphylococcal impetigo in mice.
AB  - We produced a staphylococcal impetigo model by epicutaneous inoculation in mature
      mice. A strain isolated from a human impetigo was used. Five-week-old female mice
      (ddy-strain) were used with and without pre-treatment by cyclophosphamide (Cy) (2
      mg/mouse) for 5 days. The back skin of mice was shaved by a razor blade and
      slightly abraded by sand paper. Bacterial suspension (1.4 x 10(7) CFU/0.05 ml)
      was applied on the abraded areas which were then occluded under sterile plastic
      plaster. Although intraepidermal blisters developed in non-Cy-treated mice,
      massive neutrophil infiltration obscured the changes there. Development of
      subcorneal bullae in Cy-treated mice inoculated with Staphylococcus aureus was
      first observed at 3h and enlargement of bullae was apparent at 12 h after
      inoculation. The bullae produced in Cy-treated mice contained numerous S. aureus
      bacilli. Electronmicroscopically, S. aureus cells invaded the horny layer at 1/4
      h. A clear halo was seen between S. aureus cells and horny cells. S. aureus cells
      attached to surrounding horny cells by fibril-like structures. The halo-like
      spaces became larger, coalesced and then developed into an intraepidermal
      blister. Our new method to produce human impetigo-like blister in Cy-treated
      adult mice may contribute to disclosing the mechanisms of blister formation in
      epidermis by S. aureus. Due to the thin structure of mouse epidermis, only
      specimens taken earlier than 24 h after inoculation were considered appropriate.

PMID- 1390459
TI  - Medicine, technology, and ethics: a historical perspective.

PMID- 1390458
TI  - O6-alkylguanine-DNA alkyltransferase activity in human malignant melanoma.
AB  - O6-alkylguanine has been known to be the major lesion in DNA for the cytotoxicity
      of alkylating agents and it is repaired by O6-Alkylguanine-DNA alkyltransferase
      (O6-AGT). To examine the relation of O6-AGT to the clinical characteristics in
      malignant melanoma (MM), O6-AGT activity in 13 human MM tissues was measured. The
      activity in tumor tissues varied widely from 0 to 0.11 pmol/mg protein. The
      activity in normal skin tissues was lower and less variable than in the tumors.
      The activity was not related to the tumor size or clinical stage of melanomas,
      but it was higher in tumors after chemotherapy with alkylating agents than in
      those without chemotherapy. In metastatic tissues, in primary tumors of the
      patients with metastases and in tumors of the patients with bad prognosis, the
      activity was also high. Two of the tumors, having the highest O6-AGT activity,
      were both transplantable to nude mice. These results suggest two possibilities;
      melanomas exposed to the alkylating agents may change to have high O6-AGT
      activity, followed by the resistance to such agents, or O6-AGT in melanomas may
      be originally diverse. O6-AGT activity in the tumour tissue may represent the
      effect of alkylating agents and can be used in selecting the methods of therapy.

PMID- 1390460
TI  - Innovation and change in medical technology: interactions between physicians and
      engineers.

PMID- 1390462
TI  - Ethical issues at the interface between orthopedics and bioengineering.

PMID- 1390461
TI  - Life-systems ethics and physician-engineer interactions.

PMID- 1390463
TI  - The bioengineer's obligations to patients.

PMID- 1390464
TI  - Ethics education at the engineering/medicine interface.
AB  - There is a functioning interface between engineering and medicine. There are also
      wide-spread indications in the scientific community that there is increased
      concern for ethical matters in science and that the time has arrived for more
      instruction in this area. One reason for this in bioengineering is the rapidly
      growing complexity of technology in both engineering and medical biology. The
      ensuing difficulty in communication cannot be remedied just with more technical
      information. Instead bioengineers need an improved understanding of medical
      education and practice, and medical ethics is fundamental to this. Ethical
      considerations are crucial to decision making and therefore to all areas of
      professional endeavor in bioengineering. As a framework for ethics education,
      bioengineers need to gain a better understanding both of medical education in
      general and of medical practice, particularly the case study method in education
      and the nature of decision making in medical practice. Key subject areas in
      medical ethics for bioengineers include rights and duties of physicians,
      determination of death, team ethics, patient privacy and informed consent,
      research ethics, and malpractice. An ethics curriculum for bioengineers should be
      taught using both informal but regular exposure to clinical activities and
      clinicians, and formal classroom work. In the medical ethics classroom setting,
      writing assignments are essential to provoke each student to the introspection
      and commitment needed to form a personal professional ethos.

PMID- 1390465
TI  - Laparoscopic alternatives to laparotomy: a new approach to gynaecological
      surgery.

PMID- 1390466
TI  - Survival time after AIDS in pregnancy.
AB  - OBJECTIVE: To examine the suggestion, based on theoretical considerations and
      case reports, that pregnancy decreases survival time after AIDS (acquired
      immunodeficiency syndrome). DESIGN: A total population study in Edinburgh.
      SETTING: A city with a moderately high prevalence of human immunodeficiency virus
      (HIV) infection in women. SUBJECTS: AIDS has been diagnosed in 22 women, five of
      whom had a pregnancy. MAIN OUTCOME MEASURES: Clinical characteristics, disease
      presentation, lymphocyte markers, pregnancy outcome, subsequent progress and
      survival time. RESULTS: Pregnancy was not obviously associated with a difference
      in clinical findings. The mean survival time for the three women with a pregnancy
      who died was 24 months and for the 11 women without a pregnancy it was 15 months.
      (P = 0.63 log rank test). CONCLUSIONS: The clinical presentation, severity of the
      illness and laboratory findings were not obviously different in pregnancy. All
      three women who had Pneumocystis carinii pneumonia for the first time in
      pregnancy survived this initial episode. Survival time was not obviously reduced
      by the conjunction of pregnancy with AIDS.

PMID- 1390467
TI  - Experience with the Cardial inferior vena cava filter as prophylaxis against
      pulmonary embolism in pregnant women with extensive deep venous thrombosis.
AB  - OBJECTIVE: To report the use of the Cardial inferior vena caval filter as
      prophylaxis against pulmonary embolism in pregnant women with extensive
      iliofemoral thrombosis. SETTING: Leicester Royal Infirmary. SUBJECTS: Four
      pregnant women with extensive iliofemoral thrombosis, deemed to be at high risk
      of pulmonary embolism, managed over a period of one year. TECHNIQUE: In addition
      to standard full anticoagulation with heparin, the Cardial inferior vena cava
      filter was introduced percutaneously under local anaesthesia through the
      unaffected contralateral femoral vein and positioned in the inferior cava below
      the renal veins. RESULTS: The procedure was uncomplicated and did not compromise
      feto-maternal condition. There was no evidence of pulmonary embolism after filter
      insertion. CONCLUSION: The use of inferior vena cava filters should be considered
      as an adjunct to intravenous anticoagulation in pregnant women with extensive
      deep vein thrombosis of the lower limbs.

PMID- 1390468
TI  - The effect of magnesium sulphate on blood flow velocity in the maternal retina in
      mild pre-eclampsia: a preliminary colour flow Doppler study.
AB  - OBJECTIVES: To investigate the use of colour flow Doppler ultrasound to identify
      retinal blood vessels in women with mild pre-eclampsia and to assess the effects
      of an infusion of magnesium sulphate on the baseline retinal blood flow-velocity.
      DESIGN: Prospective descriptive study. SETTING: Ben Taub Hospital, Baylor College
      of Medicine, Houston, Texas, USA. SUBJECTS: Eight women with mild pre-eclampsia.
      INTERVENTIONS: Baseline colour flow Doppler ultrasound assessment of the central
      retinal artery (CRA) and posterior ciliary artery (PCA) blood flow-velocity
      before intravenous infusion of 6 g of magnesium sulphate in 100 ml of 5% dextrose
      water over 20 min, followed by repeat Doppler measurement. MAIN OUTCOME MEASURES:
      Blood pressure, heart rate, pulsatility index (PI), resistance index (RI), angle
      corrected flow-velocity (cm/s). RESULTS: The CRA and PCA were easily and reliably
      identified. The infusion of 6 g of magnesium sulphate significantly reduced (P <
      0.05) the mean CRA PI from 1.42 (SD 0.67) to 0.93 (SD 0.18) and the mean CRA RI
      (P < 0.008) from 0.62 (SD 0.07) to 0.53 (SD 0.10). The PCA PI decreased (P =
      0.01) from 0.97 SD (0.14) to 0.78 SD (0.18) and the PCA RI decreased (P = 0.02)
      from 0.58 SD (0.07) to 0.48 SD (0.09). Angle-corrected flow-velocity decreased
      non-significantly after the magnesium sulphate infusion. CONCLUSIONS: Patients
      with pre-eclampsia have high CRA and PCA flow-velocity suggestive of vasospasm.
      Magnesium sulphate acutely vasodilates the small arteries in the retina,
      increasing retinal blood flow. Changes in the blood flow in the retina may be
      indicative of similar changes in other end-arterial branches of the internal
      carotid artery. This non-invasive Doppler method may provide a means to monitor
      the effects of therapeutic interventions in patients with pre-eclampsia.

PMID- 1390469
TI  - Placental bed biopsies in placental abruption.
AB  - OBJECTIVE: To investigate structural changes in the uteroplacental blood vessels
      in association with placental abruption. DESIGN: Prospective descriptive study.
      SUBJECTS: 18 women with clinical evidence of severe placental abruption delivered
      by caesarean section. INTERVENTIONS: Placental bed biopsies were obtained at
      caesarean section and studied histologically. RESULTS: Six specimens did not
      include trophoblast in the myometrium and were therefore not representative of
      the placental bed. Of the 12 representative specimens, seven demonstrated absence
      of physiological transformation of the utero-placental arteries (four of these
      were from hypertensive patients). Four biopsies showed abnormal vascular
      structures deep in the myometrium. One of these abnormal vessels included a fresh
      plug and extensive surrounding intramyometrial haemorrhage. CONCLUSIONS: Vascular
      malformations in association with placental abruption may be the result of
      trophoblastic invasion and could be the site of vessel rupture. Further
      descriptive and comparative studies are needed.

PMID- 1390470
TI  - The modified Pereyra procedure: a clinical and urodynamic review.
AB  - OBJECTIVE: To review the clinical and urodynamic outcome of treatment by the
      modified Pereyra procedure in 93 women with genuine stress incontinence. DESIGN:
      Retrospective review. SETTING: Harbor/UCLA Medical Center and Los Angeles County
      Women's Hospital, Los Angeles, California, USA. MAIN OUTCOME MEASURES: Clinical
      and urodynamic assessment one year after modified Pereyra procedure. RESULTS:
      Overall 82% of patients were subjectively cured while only 63% were objectively
      cured. Women with failed surgery had significantly lower pre-operative maximum
      urethral closure pressures. The procedure had a low operative and postoperative
      morbidity with no significant disturbance of voiding function noted at one year
      follow-up. CONCLUSIONS: Our results with the modified Pereyra procedure for
      stress incontinence showed a significantly lower success rate than has been
      reported from many previous studies.

PMID- 1390472
TI  - Laparoscopic treatment of infiltrative rectosigmoid colon and rectovaginal septum
      endometriosis by the technique of videolaparoscopy and the CO2 laser.
AB  - OBJECTIVE: To present the technique and results of videolaparoscopy and the CO2
      laser as a treatment for deep, infiltrative endometriosis of the rectovaginal
      septum, uterosacral ligaments, pouch of Douglas and anterior wall of the
      rectosigmoid colon. DESIGN: Observational study with 1-5 year follow up. SETTING:
      Sub-specialty practice: Endometriosis clinic and centre for special pelvic
      surgery. SUBJECTS: 185 women, aged 25-41 years. All had pelvic endometriosis and
      were referred because of the failure of previous medical and/or surgical
      treatment. INTERVENTIONS: Vaporization and excision of endometriotic implants and
      nodules, ureterolysis, ureteric stents, laparoscopic anterior rectal wall
      resection and reanastomosis, presacral neurectomy, laparoscopic hysterectomy,
      salpingo-oophorectomy and appendicectomy using the CO2 laser. MAIN OUTCOME
      MEASURES: 174 patients were followed for 1-5 years after surgery by office visit
      questionnaire or telephone interview. Eleven were lost to follow-up. RESULTS: 175
      patients were discharged within 24 h. Nine with bowel perforations and one with a
      partial bowel resection were discharged 2-4 days postoperatively. Two patients
      required ureteric stents, which were removed 6 weeks postoperatively without
      sequelae. 162 women reported moderate to complete pain relief (145 after one
      procedure, 13 after two and four after three). 12 reported persistent or worse
      pain following the surgery. Seven eventually underwent total hysterectomy, four
      had bowel resections and one had a salpingo-oophorectomy. Of 61 with infertility,
      25 achieved pregnancy. Postoperative complications included shoulder pain,
      anterior abdominal wall ecchymosis, urine retention and dyschezia for one to two
      weeks. CONCLUSIONS: Our experience suggests that rectosigmoid colon and
      infiltrative rectovaginal septum endometriosis can be effectively treated via
      videolaparoscopy in the hands of experienced endoscopic gynaecologists.

PMID- 1390471
TI  - A simplified method of laparoscopic presacral neurectomy for the treatment of
      central pelvic pain due to endometriosis.
AB  - OBJECTIVE: To describe optimal procedures and preliminary results for
      videolaparoscopic presacral neurectomy as part of the surgical treatment of
      endometriosis associated with intractable dysmenorrhoea. DESIGN: Observational
      study with follow up for at least one year. SETTING: Subspecialty practice:
      Endometriosis Clinic and Centre for Special Pelvic Surgery. SUBJECTS: Eighty five
      women (18-45 years) with endometriosis and intractable pain, referred because
      medical and surgical management had failed. Subjects without a central (midline)
      component to their discomfort were excluded. INTERVENTIONS: Excision and
      vaporization of endometriotic pathology was followed by presacral neurectomy.
      OUTCOME MEASURES: During surgery, severity of endometriosis was assessed using
      revised American Fertility Society scoring. Overall pelvic pain and dysmenorrhoea
      relief were determined by office visit, telephone interview and questionnaire at
      a minimum of one year postoperatively. RESULTS: There were no operative
      complications and all women left hospital within 24 h of surgery. Overall pain
      relief was reported by 49 (94%) of 52 patients followed. The other three subjects
      noted no pain abatement. Dysmenorrhoea was reduced in 48 (92%) whereas four (8%)
      women claimed no relief. CONCLUSIONS: Laparoscopic presacral neurectomy is an
      option for treating dysmenorrhoea and pelvic pain in selected women, but is
      indicated only if medical management has failed. Videolaparoscopic presacral
      neurectomy using the CO2 laser is safe in trained hands. Pain relief achieved is
      within the range reported for laparotomy.

PMID- 1390473
TI  - Cone biopsy: has endocervical sampling a role?
AB  - OBJECTIVE: To investigate the sensitivity, specificity and predictive value of
      endocervical sampling in women with abnormal cervical smears. DESIGN: A
      randomized study of two methods of endocervical sampling. SETTING: Colposcopy
      clinic at Aberdeen Royal Infirmary. SUBJECTS: 100 women with abnormal cervical
      smears selected for cone biopsy according to current colposcopy criteria.
      INTERVENTIONS: 53 women were randomized to have endocervical sampling with the
      Kevorkian curette and 47 to have sampling with the Medscand endocervical brush.
      MAIN OUTCOME MEASURES: Cytology and histology results from endocervical sampling
      compared with cone biopsy histology. RESULTS: The overall sensitivity of
      endocervical sampling was 56%, with a false negative rate of 44% and a negative
      predictive value of 26%. CONCLUSIONS: Endocervical sampling should not influence
      management when colposcopy is unsatisfactory.

PMID- 1390474
TI  - Genital tract infections associated with the intrauterine contraceptive device
      can be reduced by inserting the threads into the uterine cavity.
AB  - OBJECTIVE: To study the influence of the position of the threads of an
      intrauterine contraceptive device (IUCD) on the development of genital tract
      infection. DESIGN: A multicentre randomized controlled trial. SUBJECTS: Women
      requesting an IUCD. INTERVENTIONS: The women were randomized to be fitted with an
      IUCD either with the threads contained in the uterine cavity (threads-up group)
      (n = 208) or passing through the cervix to the vagina in the usual way (threads
      down group) (n = 237). Multiple centre study with follow-up at three months, 1
      and 2 years. At the final visit 'missing' threads were retrieved using a
      disposable instrument (Retrievette). MAIN OUTCOME MEASURES: The occurrence of
      infection in the lower or upper genital tract. RESULTS: 63 women in the threads
      up group and 78 in the threads-down groups dropped out. Previous gynaecological
      infection was reported by 21 and 48 women in the threads-up and threads-down
      group, respectively (odds ratio 0.44, 95% CI 0.24 to 0.79), 21 and 53 subjects
      had signs of infection at gynaecological examination (odds ratio 0.39, 95% CI
      0.21 to 0.69) and a wet-smear was pathological in 33 and 79 (odds ratio 0.38, 95%
      CI 0.23 to 0.61). In the threads-up group the vaginal pH was also lower at the
      final check up after 2 years. Spontaneous descent of the threads occurred in 11%
      of the threads-up group and in six women in the threads-down group the threads
      were in the cervix. In 93 women the threads were easily retrieved by means of the
      Retrievette, four women insisted on the threads remaining in the uterus and in 18
      thread removal was performed under local or general anaesthesia. CONCLUSIONS:
      Infectious complications in women using an IUCD are more frequent if the threads
      lead from the uterine cavity to the vagina. This problem can be reduced by
      inserting the threads so that they remain entirely within the uterine cavity, a
      feasible procedure now that an effective instrument for IUCD thread retrieval is
      available.

PMID- 1390475
TI  - Stimulation of vasopressin release in women with primary dysmenorrhoea and after
      oral contraceptive treatment--effect on uterine contractility.
AB  - OBJECTIVE: To study aspects of the aetiology of primary dysmenorrhoea and
      mechanisms underlying the therapeutic effect in this condition of an oral
      contraceptive. INTERVENTION: Intrauterine pressure was recorded before and during
      infusion of hypertonic saline (5% NaCl, 0.06 ml/kg/min) over 75 min on the first
      day of bleeding in women with dysmenorrhoea and after 3 weeks of oral
      contraceptive treatment. Plasma sampling every 15 min of ongoing infusion for the
      estimation of osmolality, arginine vasopressin, oxytocin and the prostaglandin
      (PG) F-metabolite, 15-keto-13,14-dihydro-PGF2 alpha. SUBJECTS: Ten healthy
      nulliparous women with moderate to severe primary dysmenorrhoea. MAIN OUTCOME
      MEASURES: Plasma levels of posterior pituitary hormones and the PGF-metabolite.
      Total pressure area (TPA) of the recording curve. RESULTS: In dysmenorrhoea
      before infusion the plasma concentration of vasopressin was in mean 2.18,
      oxytocin 5.05 and the PGF-metabolite 321.5 pmol/l, and the TPA 3.8 kPa x 10 min.
      After oral contraceptive treatment the vasopressin level and the TPA were
      significantly reduced. At both sessions apart from intensifying the pain, the
      saline infusion increased vasopressin and oxytocin levels as well as the TPA,
      whereas the concentration of the PGF-metabolite at both sessions decreased.
      CONCLUSION: Confirmation is provided of the elevated secretion of arginine
      vasopressin and PGF2 alpha, as well as increased uterine activity in primary
      dysmenorrhoea. The observations are in agreement with the concept that a lowered
      level of vasopressin and a decreased uterine activity contributes to the
      beneficial effect of OCs in the condition. Stimulation of the secretion of
      vasopressin increases the uterine activity and symptoms of primary dysmenorrhoea,
      but results suggest that this effect does not involve a mechanism of increased
      PGF-synthesis. The role of oxytocin in dysmenorrhoea can not yet be defined.

PMID- 1390476
TI  - A four-year follow-up of hearing and development in children exposed in utero to
      vibro-acoustic stimulation.
AB  - OBJECTIVE: To obtain information of hearing and neuro-development in children
      exposed to vibro-acoustic stimulation in utero. DESIGN: Information collected
      from Swedish child care programmes. SETTING: Department of Obstetrics and
      Gynaecology, Karolinska Institutet, Danderyd University Hospital, Sweden.
      SUBJECTS: Children of 460 mothers exposed to vibro-acoustic stimulation for the
      assessment of fetal well-being during high- and low-risk pregnancies during 1985
      1987. MAIN OUTCOME MEASURES: Auditory test (20-25 dB at eight frequencies between
      500 and 8000 Hz) and general neurological examination at four years of age.
      RESULTS: No hearing damage or neuro-developmental abnormalities that could be
      connected to the vibro-acoustic stimulation were found. CONCLUSIONS: Vibro
      acoustic stimulation, as applied in clinical practice, did not endanger either
      neurological development or hearing in children exposed in utero.

PMID- 1390477
TI  - Atypical female intersex.

PMID- 1390478
TI  - Intermittent abdominal decompression: an option for prevention of intrauterine
      growth retardation.

PMID- 1390479
TI  - The effect of thyroxine replacement on menstrual blood loss in a hypothyroid
      patient.

PMID- 1390480
TI  - Unexpected pathological findings in uterine prolapse: a 12-month audit.

PMID- 1390481
TI  - Sex ratio, testosterone and postpartum thyroid dysfunction.

PMID- 1390482
TI  - Abortion in Poland, commentary.

PMID- 1390483
TI  - Sarcoidosis and inflammatory eye disease.

PMID- 1390484
TI  - The treatment of periocular basal cell carcinomas by radiotherapy.
AB  - Experience in the treatment of periocular basal cell carcinoma is described.
      Excellent local control rates and minimal morbidity have been achieved in a
      series of 128 tumours occurring in 127 patients with a minimum 3 year follow-up.

PMID- 1390485
TI  - Impression cytology of conjunctival melanosis and melanoma.
AB  - Impression cytology using cellulose acetate paper has been used in various ocular
      surface disorders as a simple non-invasive diagnostic test. To assess its value
      in differentiating melanocytic tumours, 24 patients with a range of pigmented
      lesions of the conjunctiva were examined using this technique. Cytological and
      histological diagnoses were compared in 23 cases. In 73% of cases impression
      cytology predicted the histological diagnosis by detection of superficial
      atypical melanocytes and their proportion relative to benign epithelial cells.
      This pilot study shows impression cytology to be a useful diagnostic aid in the
      differentiation of pigmented tumours of the bulbar conjunctiva.

PMID- 1390486
TI  - Retinopathy of prematurity in surfactant treated infants.
AB  - Seventy six babies of less than 1500 g birth weight who had surfactant
      replacement therapy for severe respiratory distress syndrome were studied to
      assess the presence and stage of subsequent retinopathy of prematurity (ROP). A
      control group of 90 babies, matched for birth weight and gestational age, who did
      not have surfactant therapy were also studied. Threshold ROP or greater was found
      in 1.7% of the surfactant group and 7.8% of the controls. For the babies of less
      than 1000 g birth weight 4.0% of the surfactant babies and 16.3% of the controls
      reached threshold disease or greater. It is concluded that surfactant therapy is
      not associated with an increased incidence or severity of severe ROP in this
      preterm population.

PMID- 1390487
TI  - PhXA34--a prostaglandin F2 alpha analogue. Effect on intraocular pressure in
      patients with ocular hypertension.
AB  - PhXA34, a prostaglandin analogue, was given topically to 40 patients with
      untreated ocular hypertension in a double masked randomised study. One single
      dose of 0.3, 1, 3, 10 micrograms, or placebo (vehicle) was given to one eye of
      each patient. A dose related IOP reduction ranging from 11 to 35% was observed
      with a maximal effect with 3 and 10 micrograms PhXA34. No hyperaemia was seen
      except after 10 micrograms PhXA34, where a mild to moderate hyperaemia was seen
      from 8 hours with a duration of up to 24 hours. Mild foreign body sensation in
      the PhXA34-treated eye was noted by three patients. No cells or flare were seen.

PMID- 1390488
TI  - Twin study on cup/disc ratio of the optic nerve head.
AB  - Seventeen healthy twin pairs (10 monozygotic and seven dizygotic) from the
      Finnish Twin Cohort Study were examined to study the impact of heredity v
      environment in the determination of cup-to-disc area ratio. These twins were free
      from any known eye disease. The cup/disc ratio was determined using stereo
      photography and a computer assisted analysis technique. The zygosity of all twin
      pairs was confirmed with the DNA 'fingerprint' technique. The intrapair
      correlations were high among monozygotic pairs compared with those among
      dizygotic twin pairs. The difference of cup/disc area ratios between the right
      eyes of members of monozygotic twin pairs was statistically significantly smaller
      than that of dizygotic twin pairs (p < 0.001). The same was true for left eyes (p
      < 0.01). This result confirms a genetic determination in cup/disc area ratio in
      normal eyes.

PMID- 1390489
TI  - Cystoid macular oedema following cataract extraction in patients with diabetes.
AB  - The course of cystoid macular oedema (CMO) following extracapsular cataract
      extraction with posterior chamber intraocular lens implantation was prospectively
      studied in 44 eyes of 44 consecutive diabetic patients without preoperative CMO.
      In 50% of eyes CMO was observed 6 weeks after surgery and in 25% was still
      present at 1 year. The preoperative presence of diabetic retinopathy
      significantly affected the postoperative onset and persistence of CMO. CMO
      occurred postoperatively in only 32% of eyes without pre-existing diabetic
      retinopathy and in 81% of eyes with pre-existing diabetic retinopathy (p < 0.05).
      CMO persisted at 1 year after surgery in only 7% of eyes without pre-existing
      diabetic retinopathy and in 56% of eyes in which diabetic retinopathy persisted
      (p < 0.01). Angiographic CMO (that is, detectable only on fluorescein
      angiography) was more common than clinical CMO (detectable on ophthalmoscopic
      examination as well) in eyes with no pre-existing diabetic retinopathy, whereas
      clinical CMO was seen more often than angiographic CMO when diabetic retinopathy
      was present preoperatively (p < 0.01). The course and final visual outcome of
      angiographic CMO were more favourable than in clinical CMO. Final visual acuity
      of at least 6/12 was achieved in 86% of eyes with angiographic CMO and in only
      33% of eyes with clinical CMO. On the basis of the above findings we believe that
      cataract extraction should not be recommended for eyes with pre-existing diabetic
      retinopathy until the vision has deteriorated to at least 6/30-6/60.

PMID- 1390490
TI  - Ophthalmic pain following cataract surgery: a comparison between local and
      general anaesthesia.
AB  - Ophthalmic pain following uncomplicated extracapsular cataract surgery was
      assessed postoperatively in 61 patients; 55% undergoing ophthalmic surgery had no
      pain or discomfort postoperatively, and 32% reported slight discomfort.
      Approximately 8% of patients reported mild pain and the remaining 5% experienced
      moderate to severe pain. Local anaesthesia was shown to be more comfortable
      postoperatively than general anaesthesia in the immediate postoperative period
      with both groups receiving similar amounts of postoperative analgesics.

PMID- 1390492
TI  - Strampelli's osteo-odonto-keratoprosthesis. Clinical and histological long-term
      features of three prostheses.
AB  - The histological features are reported of osteo-odonto-acrylic laminae removed
      from three patients who for differing underlying causes received Strampelli's
      osteo-odonto-keratoprostheses (OOK) 20, 16, and 12 years previously. It appears
      that preservation of the alveolar-dental ligament plays a definitive role in the
      maintenance of the prosthesis. If this tissue undergoes necrosis as a consequence
      of an inflammatory disease the implanted material is eventually lost. However
      when no such event occurs the OOK is well preserved and well tolerated even 20
      years after implantation.

PMID- 1390491
TI  - The course of diabetic retinopathy following cataract surgery in eyes previously
      treated by laser photocoagulation.
AB  - The course of diabetic retinopathy following extracapsular cataract extraction
      with posterior chamber lens implantation in eyes previously treated by laser
      photocoagulation for diabetic retinopathy was retrospectively studied in 33 eyes
      (33 patients). In 20 eyes (61%) there was no change in the retinal status
      postoperatively. In 13 (39%) there was postoperative progression of diabetic
      retinopathy compared with the fellow non-operated eye, in which progression
      occurred in nine eyes (27%). The severity of the preoperative status affected the
      incidence of progression. Four eyes (12%) developed complications of diabetic
      retinopathy--that is, rubeosis iridis and vitreous haemorrhage--which regressed
      after lasering. Cystoid macular oedema developed in 13 eyes (39%) and its
      incidence varied according to the postoperative course of diabetic retinopathy.
      The majority of the eyes showed a postoperative improvement in vision.

PMID- 1390493
TI  - The role of preservatives in the conjunctival toxicity of subconjunctival
      gentamicin injection.
AB  - Subconjunctival gentamicin was identified as the cause of conjunctival chemosis
      and capillary closure in a recent study conducted in this department. The
      gentamicin preparation used in the study contained preservatives. The current
      prospective study was set up to investigate the role of preservatives in the
      conjunctival toxicity of subconjunctival gentamicin. Seventy five patients
      undergoing cataract surgery were enrolled in the study. They were split into
      three groups of 25 each. Group A patients were given a subconjunctival injection
      of a preservative-free aqueous solution of gentamicin at the end of the cataract
      procedure. Group B patients were given a subconjunctival injection of gentamicin
      containing sodium metabisulphite and disodium edetate as preservatives at the end
      of the cataract procedure. Group C was the control group where patients were not
      given any subconjunctival injection. The incidence of severity of conjunctival
      chemosis were observed in the three groups. The difference between groups A and B
      patients who received preservative-free gentamicin and gentamicin with
      preservatives respectively was significant (p < 0.02).

PMID- 1390495
TI  - Low dose cyclosporin A versus pulsed cyclophosphamide in Behcet's syndrome: a
      single masked trial.
AB  - A single masked trial of cyclosporin A 5 mg/kg/day versus monthly 1 g intravenous
      boluses of cyclophosphamide was conducted among 23 patients with Behcet's
      syndrome and active, potentially reversible uveitis. The trial was unmasked after
      a mean of 12 (SD 2) months for the cyclosporin A group (n = 12) and a mean of 10
      (SD 3) months for the cyclophosphamide group (n = 11). During the initial 6
      months the visual acuity significantly improved (p < 0.001) in the cyclosporin A
      group whereas this was not observed in the cyclophosphamide group. The subsequent
      follow-up of patients up to 24 months suggested that the initial improvement in
      visual acuity with cyclosporin A was not sustained. More extensive and especially
      long-term studies of cyclosporin A in the uveitis of Behcet's syndrome are
      warranted.

PMID- 1390494
TI  - Cataract surgery in Fuchs' heterochromic iridocyclitis.
AB  - Eighteen eyes in 17 patients with Fuchs' heterochromic iridocyclitis underwent
      cataract extraction with or without intraocular lens implantation (17
      extracapsular and one intracapsular). Intraoperative complications included
      hyphaema, poor pupillary dilatations, and localised zonule dehiscence with
      vitreous loss. Only four eyes developed a marked anterior uveitus (two
      pseudophakic and two aphakic) which resolved within 2 weeks with topical
      steroids. Three eyes developed a rise in intraocular pressure (IOP) to more than
      30 mm Hg on the first postoperative day. In all three eyes the IOP returned to
      normal off all therapy within 1 week. In one of three eyes preoperative glaucoma
      was made worse following surgery. Visual acuity testing revealed that 15 eyes
      (83.3%) achieved 6/12 vision or better. Lamellar macular hole, pre-existing
      macular scar, and pre-existing retinal detachment accounted for the poor visual
      result.

PMID- 1390496
TI  - Ophthalmic zoster.

PMID- 1390497
TI  - Lid melanoma and parkinsonism.
AB  - This is a case report of a patient with parkinsonism on levodopa therapy who
      developed a lid margin melanoma. The possible association is discussed.

PMID- 1390498
TI  - Capsular 'pits' in the human lens.
AB  - The lens capsule is an atypical basement membrane surrounding the lens epithelial
      cells and lens fibres which make up the remainder of the human lens. A seemingly
      unreported morphological change visible in the lens capsule with the
      biomicroscope is described.

PMID- 1390499
TI  - Bilateral macular coloboma and pigmented paravenous retinochoroidal atrophy.
AB  - A patient had bilateral macular coloboma with aggregations of pigment clumps
      located perivascularly, predominantly paravenously, and in other parts of the
      retina. The Toxoplasma IgG antibody was negative. The diagnosis of bilateral
      macular coloboma with pigmented paravenous retinochoroidal atrophy was made and
      seemed to be a developmental abnormality in origin.

PMID- 1390500
TI  - Metastatic endophthalmitis caused by Clostridium perfringens.
AB  - A case of metastatic endophthalmitis due to Clostridium perfringens originating
      from the biliary tract is reported. The grave visual prognosis and the importance
      of early detection and treatment of the primary source of infection are
      emphasised.

PMID- 1390502
TI  - Fluphenazine induced welding arc maculopathy.

PMID- 1390501
TI  - Peribulbar anaesthesia.

PMID- 1390503
TI  - Aspirin and cataract.

PMID- 1390504
TI  - Does aspirin affect the rate of cataract formation? Cross-sectional results
      during a randomised double-blind placebo controlled trial to prevent serious
      vascular events. UK-TIA Study Group.
AB  - A total of 2435 patients with transient ischaemic attack or minor ischaemic
      stroke were entered into the UK-TIA aspirin trial and randomised to treatment
      with aspirin 1200 mg/day, aspirin 300 mg/day, or placebo. At a single point in
      time during the trial patients were examined ophthalmoscopically for evidence of
      cataracts. The length of time that each patient had been participating in the
      trial at the time of ophthalmic examination varied from 1 to 5 years. The
      prevalence of cataracts was similar in patients allocated aspirin and patients
      allocated placebo irrespective of the length of time that they had been in the
      trial. These findings suggest that aspirin taken in a dose of 300 to 1200 mg
      daily for a few years does not prevent cataracts.

PMID- 1390505
TI  - Do patients like day case cataract surgery?
AB  - One hundred and fifty consecutive questionnaires following day case cataract
      surgery showed that 87% of the patients would choose day surgery again. The
      questionnaires were directed at the patients' attitudes to day surgery for their
      cataracts. There was overwhelming acceptance of the travelling and inconvenience
      involved.

PMID- 1390506
TI  - The dark perimetric stimulus.
AB  - We determined the disappearance eccentricities of dark and bright stimuli of
      equal size in the inferonasal central visual field using the oculokinetic
      perimetry technique at different levels of surrounding illumination. The results
      suggest that a dark stimulus on a bright background has a smaller 'isoptre' than
      an equally bright stimulus on a dark background, and that variation of ambient
      illumination and consequent alteration of background luminance have less effect
      on the visibility of a dark stimulus than a bright one.

PMID- 1390507
TI  - Red eyes in renal failure.
AB  - Of 57 patients with chronic renal failure who all had deposition of calcium salts
      in the conjunctival and corneal tissue two developed a brief episode of painful
      irritation and redness of the conjunctiva and subconjunctiva. This hyperaemia was
      adjacent to erosions of the corneal epithelium of the eye as a consequence of
      exfoliation of calcium concretions from the superficial corneal epithelium. Eight
      patients showed inflammatory reactions of the conjunctivae that were clinically
      identical to inflamed pingueculae. Three patients showed an inflammatory reaction
      of the eye that was characterised by a waxy red, more or less diffuse, episcleral
      and conjunctival hyperaemia extending beyond the palpebral fissure. The average
      value of the serum calcium concentration in these patients was particularly high
      and statistically significantly higher than in patients with calcification but
      without inflammatory signs and also higher than in patients who showed
      pingueculitis. We propose to reserve the term 'red eye of renal failure' for the
      latter group of patients.

PMID- 1390508
TI  - Ulcerative blepharitis in atopic patients--is Candida species the causative
      agent?
AB  - A total of 50 patients suffering both from atopic skin disease and different
      clinical forms of blepharitis have been included in this study. Microbiological
      investigations (for bacteria and fungi) of the lid margins were performed in all
      cases. In 21 (42%) of the patients an ulcerative blepharitis which heavily
      involved the follicles of the lashes was diagnosed. The remaining 29 cases
      presented with blepharitis of the squamous type. The cultures revealed that 19 of
      the 21 patients with ulcerative blepharitis were found to grow Candida species,
      whereas fungi could not be detected in any of the other cases of blepharitis. The
      frequencies of concomitant bacterial organisms found in the cultures were similar
      in both groups. As atopic patients are known to exhibit a defect in their cell
      mediated immunity and possibly also a defective IgA antibody response it is a
      widely accepted assumption that these immunological changes are contributing
      factors to the development of a localised inflammation of the lids which is
      initiated by a variety of micro-organisms. We postulate that when Candida species
      happen to coincide with severe inflammation in atopic patients a blepharitis of
      the ulcerative type will develop or deteriorate thereby implying that these
      microorganisms may play an important role in the development or deterioration of
      this severe chronic inflammation. It is therefore advisable to perform repeated
      scrapings and cultures in every case of recalcitrant blepharitis.

PMID- 1390509
TI  - Retinal blood flow alterations associated with scleral buckling and encircling
      procedures.
AB  - The bidirectional laser Doppler technique and monochromatic photography were used
      to measure the absolute blood flow rate in the major temporal retinal arteries in
      seven patients following unilateral scleral buckling and encircling procedures,
      and in two patients before and after removal of scleral buckling elements. In the
      seven patients who had undergone uncomplicated scleral buckling procedures the
      arterial flow rates were on average 50% lower (p = 0.01) in the surgically
      treated eyes than in the contralateral eyes. Removal of scleral buckling elements
      in two patients produced increases of 73% and 44% in arterial blood flow rates.

PMID- 1390510
TI  - Onset of retinopathy of prematurity as related to postnatal and postconceptional
      age.
AB  - The hypothesis that both perinatal events and stage of retinal development are
      important factors in determining the age at onset of retinopathy of prematurity
      (ROP) was tested by comparing gestational age at birth with postnatal and
      postconceptional age when ROP (using ICROP) was first seen. The study population
      consisted of 207 infants (111 placebo (P) treated, 96 vitamin E (E) treated) who
      developed ROP among a group of 914 premature infants (460 P, 454 E) enrolled in a
      randomised clinical trial of the effect of prophylactic use of vitamin E at
      pharmacological serum levels on incidence and severity of retinopathy. The mean
      postnatal age at onset of retinopathy was delayed in E treated infants compared
      with P treated infants by 1.4 weeks (t = 4.004, p < 0.0001). For both P and E
      treated infants postnatal age at onset of ROP (which reflects the state of
      retinal development at which birth insults occur) and postconceptional age at
      onset of ROP which defines state of maturity) were correlated with gestational
      age at birth. This suggests that both the event of premature birth and the extent
      of retinal development are important in determining when ROP will first be
      observed.

PMID- 1390511
TI  - Cryotherapy for retinopathy of prematurity--a prospective study.
AB  - Cryotherapy has been shown to reduce the unfavourable outcome in retinopathy of
      prematurity with stage 3 threshold disease by 50%. In a prospective study
      cryotherapy had a favourable outcome in 13 of 24 eyes with stage 3 threshold
      disease. The visual outcome, refraction, and complications of cryotherapy are
      discussed.

PMID- 1390512
TI  - Corneal diameter in premature infants.
AB  - The size of the cornea is important in the diagnosis of primary infantile
      glaucoma. Reference values regarding eyes of premature infants are scarce. Such
      data are of special importance in areas such as the Middle East where infantile
      glaucoma is common and often evident already at birth. The authors have measured
      the horizontal corneal diameter of the eyes of 127 premature Saudi infants with a
      gestational age between 23 and 36 weeks and a birth weight ranging from 540 g to
      4720 g. The corneal diameter ranged from 7.75 mm to 10 mm. The smallest diameter
      (7.75 mm) was found in an infant with a gestational age of 23 weeks and having a
      birth weight of 520 g. The largest diameter (10 mm) belonged to two infants with
      a gestational age of 34 and 35 weeks and a birth weight of 2250 g and 2240 g
      respectively. Corneal diameter was positively correlated (p < 0.001) with
      gestational age and birth weight. Graphs depicting the regression line of corneal
      diameter on gestational age and of corneal diameter on birth weight together with
      the 95% confidence limits for individual values are provided for reference.

PMID- 1390513
TI  - Pigmented epithelial tumours of the conjunctiva.
AB  - Two out of 60 conjunctival epithelial tumours reviewed between 1973 and 1989 were
      found to be pigmented. One tumour was a pigmented papilloma and the other a
      pigmented squamous cell carcinoma. The melanin pigment was found in epithelial
      tumour cells as well as in macrophages, dendritic melanocytes, and Langerhans
      cells. The distinction between the latter two types of cells was possible in one
      of the tumours only. Both tumours were found in dark-skinned white patients
      without any evidence of conjunctival acquired melanosis.

PMID- 1390514
TI  - Spontaneous subconjunctival haemorrhage--a sign of hypertension?
AB  - The relationship between the condition of spontaneous subconjunctival haemorrhage
      (SCH) and hypertension was investigated. Seventy eight patients with SCH and 78
      controls with unrelated ophthalmic conditions were compared. Blood pressure (BP)
      was significantly higher at presentation in the group with SCH at 149 (SD 27)/89
      (SD 15) versus 142 (SD 25)/81 (SD 12). The proportion of hypertensives by WHO
      criteria (systolic blood pressure > 160 and/or diastolic blood pressure >95) was
      46% on presentation compared with 23% of the control group. The morphology of the
      lesion did not influence the association with hypertension although there was a
      suggestion that the group with raised haemorrhages had a tendency to higher
      systolic blood pressure. It is recommended that all patients with SCH have their
      BP checked; this will result in the diagnosis of a significant number of new
      hypertensives.

PMID- 1390515
TI  - Optimal postoperative refraction for good unaided near and distance vision with
      monofocal intraocular lenses.
AB  - Forty five eyes with up to 2 dioptres of myopic astigmatism and up to 1 dioptre
      sphere either plus or minus following cataract extraction and implantation of a
      monofocal intraocular lens were examined to assess their unaided visual acuities.
      Forty three percent were able to see 6/12 and N8, and 60% were able to see 6/12
      and N10. Subjects with between 1 and 2 dioptres of myopic astigmatism and
      virtually no sphere were able to see 6/12 and N10 in 82% of cases. This study
      confirms the benefits to both distance and near vision of myopic astigmatism as
      an alternative to multifocal intraocular lenses.

PMID- 1390516
TI  - Calculation of the power of anterior chamber implants.
AB  - Ninety seven eyes with anterior chamber implants and a best corrected visual
      acuity of at least 6/12 were studied, firstly, to compare the predictive
      accuracies of the commonly used formulas for intraocular lens (IOL) power
      calculation and, secondly, to determine the effect of optimising the 'A' constant
      on the predictive accuracies of the empirical Sanders-Retzlaff-Kraff (SRK)
      formulas. The accuracies of the empirical formulas (SRK and SRK II) were
      generally similar to those of the theoretical formulas (Binkhorst II and
      Colenbrander-Hoffer). However the original SRK formula was more accurate than the
      two theoretical formulas in long eyes and in all eyes overall. Optimisation of
      the 'A' constants did not improve the predictive accuracy of the empirical SRK
      formulas.

PMID- 1390518
TI  - Malignant melanoma of the optic nerve head in a case of oculodermal
      melanocytosis.
AB  - Malignant melanoma of the uveal tract, orbit, and brain have been reported to
      occur in patients with oculodermal melanocytosis. A 60-year-old Caucasian man
      with oculodermal melanocytosis developed a malignant melanoma of the optic nerve
      head in the left eye. This case is the first reported example of a malignant
      melanoma developing in the optic nerve associated with oculodermal melanocytosis.
      After presentation the patient refused surgery for 19 months and the progression
      of the tumour necessitated an exenteration of the orbit.

PMID- 1390517
TI  - Bilateral optic nerve sheath meningiomas in a patient with neurofibromatosis type
      2.
AB  - A 34-year-old woman who presented with hearing loss and tinnitus was found to
      have reduced vision bilaterally. Computed tomography scan revealed bilateral
      acoustic neuromas and bilateral optic nerve sheath meningiomas. The presence of
      bilateral acoustic neuromas fulfils the criteria for the diagnosis of central
      neurofibromatosis (neurofibromatosis type 2). Although this is the first report
      of bilateral optic nerve sheath meningioma in neurofibromatosis type 2,
      meningiomas are commoner in this dominantly inherited disorder, than in its
      absence and both forms of central nervous system tumour may be caused by loss of
      tumour suppressor genes on chromosome 22.

PMID- 1390519
TI  - Alice in Wonderland syndrome as an initial manifestation of Epstein-Barr virus
      infection.
AB  - We present a patient with serologically confirmed Epstein-Barr virus (EBV)
      infection who had illusions of size, shape, and colour of objects but none of the
      typical symptoms and signs peculiar to infectious mononucleosis (IM) except sore
      throat which developed 2 weeks after the initial visual disturbances. The bizarre
      feelings about the images of body and objects are called the 'Alice in Wonderland
      syndrome' due to the similarity with Alice's dreams. The same symptomatology
      including visual metamorphosia is defined in patients with migraine, epilepsy,
      intoxication due to hallucinogenic drugs, schizophrenia, hyperpyrexia, and
      cerebral lesions. Alice in Wonderland syndrome has also been reported in the
      course of IM.

PMID- 1390520
TI  - Laser card.

PMID- 1390521
TI  - Delayed ciliochoroidal detachment following intraocular lens implantation.

PMID- 1390522
TI  - Installing a database for the retrieval of fluorescein angiograms.

PMID- 1390523
TI  - Inhibition of intraocular fibrin formation with annexin V.
AB  - Annexin V is a member of the calcium- and phospholipid-binding proteins, known to
      have an antithrombotic effect. For the first time, we have tested its ability to
      prevent intraocular postoperative fibrin formation in a standardised rabbit model
      and compared its effect with that of heparin. Annexin V, 20 micrograms and 60
      micrograms, injected in the anterior chamber post-operatively, significantly
      reduced the area of the fibrin clot and its time to clearing. Annexin V appeared
      to be as efficient as heparin. It probably acts by preventing phospholipids from
      playing their role in the coagulation cascade which leads to fibrin formation.
      Furthermore, annexin V has an anti-inflammatory effect by protecting
      phospholipids from phospholipase A2 activity. Therefore, annexin V might be
      considered as a new therapeutic agent acting both on fibrin formation and
      inflammatory processes.

PMID- 1390524
TI  - Continued breakdown of the blood aqueous barrier following cataract surgery.
AB  - Following routine extracapsular cataract and posterior chamber implant surgery,
      recovery of the blood aqueous barrier (BAB) was quantified by sequential anterior
      chamber fluorophotometry. This was correlated with surgical details and
      postoperative findings to ascertain those factors which were related to excessive
      damage of the BAB immediately after surgery and to failure to recover a normal
      BAB by 3 months postoperatively. A cohort of 84 patients was followed. In the
      early postoperative period excessive levels of damage to the BAB were related to
      iris damage (p < 0.01) and diabetes mellitus (p < 0.01). By 3 months, 79% of the
      eyes had recovered normal BABs and 21% (18 eyes) had persisting excessive
      fluorescence which correlated with an abnormal pupil shape (p < 0.02) and the
      development of posterior synechiae (p < 0.001).

PMID- 1390525
TI  - Immunoimaging of choroidal melanoma: assessment of its diagnostic accuracy and
      limitations in 101 cases.
AB  - Immunoscintigraphy (IS) was performed on 101 patients with space occupying
      intraocular lesions including choroidal melanomas (85), choroidal naevi (11), non
      melanoma metastases (three), and other melanoma simulating lesions (two).
      Scintigraphic images with conventional and emission computer tomography
      techniques were obtained after the intravenous injection of 99mTc-labelled
      F(ab')2 fragments of monoclonal antibody (MoAb) 225.28S directed against the high
      molecular weight-melanoma associated antigen (HMW-MAA). Immunohistochemistry was
      performed on sections of four out of 10 melanoma-containing eyes to confirm MoAb
      binding. IS demonstrated positive scans in 66 out of 85 choroidal melanomas,
      offering a sensitivity of 78%. Sensitivity was dependent on the lesion size. True
      negative results were obtained in 15 out of 16 non-melanoma lesions (specificity
      94%). False positive antibody accumulation was found in one patient with a post
      traumatic subretinal haemorrhage. Immunohistochemistry demonstrated positive MoAb
      225.28S binding in all melanoma sections. In summary IS offered substantial
      sensitivity and specificity in the differentiation of intraocular lesions,
      particularly choroidal melanomas, naevi, and metastases. In combination with
      other diagnostic procedures such as ultrasound echography and fluorescein
      angiography IS proved to be a valuable method in the diagnosis of choroidal
      melanoma.

PMID- 1390526
TI  - Detection of colour vision abnormalities in uncomplicated type 1 diabetic
      patients with angiographically normal retinas.
AB  - Colour vision function was assessed in 38 non-complicated type 1 diabetic
      patients in whom fluorescein angiography was normal, and was compared with that
      in 36 age-matched, non-diabetic controls. All of the patients were healthy and
      none were taking medication except insulin. The eye examination, which was normal
      in every patient, included the Ishihara and City University tests, measurement of
      Snellen acuity, slit-lamp examination, tonometry, and fundal photography as well
      as fluorescein angiography. Colour discrimination ability was measured with the
      Farnsworth-Munsell 100-hue test. Mean (SE) 100-hue test error score for the
      diabetic group was 86.8 (8.1) compared with 28.2 (3.3) for controls, p<<0.001.
      There was no relation between colour vision abnormalities and diabetes duration
      (r = 0, p>0.05), blood glucose at the time the colour tests were performed (r =
      0.4, p > 0.05), most recent glycated haemoglobin result (r = 0.3, p>0.05), or the
      mean of all previous glycated haemoglobin results (r = 0, p>0.05). It is
      concluded that colour discrimination may be abnormal in uncomplicated type 1
      diabetic patients before the onset of retinopathy, and that colour discrimination
      losses in diabetes may not be of vascular aetiology.

PMID- 1390528
TI  - Confocal imaging of the fundus using a scanning laser ophthalmoscope.
AB  - A confocal scanning laser ophthalmoscope (cSLO) was used to examine the effects
      of confocal optics on the image of the human fundus in vivo. Patients from a
      retinal clinic and a glaucoma clinic were examined using the cSLO in the confocal
      mode. A degree of optical sectioning could be achieved, and the results agree
      with a best axial resolution of 300 microns measured in a model eye. The main
      advantage of using a confocal system was found to be the improved contrast of the
      images. This improved the resolution of structures such as the lamina cribrosa
      and optic disc drusen which are seen in low contrast in conventional images. The
      improved contrast of the confocal images is partly achieved by excluding light
      which has been scattered within the plane of focus. Structures which multiply
      scatter light will become less visible with confocal optics and hard exudates
      were found to be an example of such a structure. The cSLO and the fundus camera
      are seen as complementary instruments rather than as alternatives for imaging the
      fundus. It is envisaged that confocal imaging will enable details of the fundus
      to be revealed which are at present not seen in conventional images.

PMID- 1390527
TI  - Abnormal dark adaptation kinetics in autosomal dominant sector retinitis
      pigmentosa due to rod opsin mutation.
AB  - The time course of dark adaptation was measured in 10 subjects from three
      families with autosomal dominant sector retinitis pigmentosa (RP) due to
      mutations in the first exon of the rod opsin gene. In each subject cone
      adaptation and the early part of the recovery of rod sensitivity followed the
      normal time course, but the later phase of rod adaptation was markedly prolonged.
      The recovery of rod sensitivity is much slower than that reported in any other
      outer retinal dystrophy. Using a model based upon primate data of rod outer
      segment length and turnover, we have calculated that the delayed phase of the
      recovery of rod sensitivity in the RP patients tested following strong light
      adaptation could be due in part to formation of new disc membrane with its normal
      concentration of rhodopsin rather than in situ regeneration of photopigment.

PMID- 1390529
TI  - The effects of subconjunctival betamethasone on the blood aqueous barrier
      following cataract surgery: a double-blind randomised prospective study.
AB  - The aim of this double-blind randomised prospective study was to assess the
      effect of subconjunctival Betnesol (betamethasone sodium phosphate 0.1%) on the
      recovery of the blood aqueous barrier (BAB) following cataract surgery in
      uncomplicated eyes. Twenty patients [10 male, mean age 71.4 (SD 12.7) years]
      admitted for routine cataract surgery were randomised into two groups. All
      patients recruited into the study were free of other ocular disease and were not
      taking any anti-inflammatory medication. Group A received a subconjunctival
      injection of cefuroxime (125 mg) alone while group B received a subconjunctival
      injection of both cefuroxime and Betnesol. All surgery was performed by a single
      surgeon using a standardised surgical technique and all patients received the
      same postoperative medication. The Kowa laser flare cell meter was used to
      measure aqueous flare and cells preoperatively and on the first, second, and
      seventh postoperative day, and at 1 and 3 months following surgery. The code was
      broken only after all patients had been followed-up for 3 months postoperatively.
      There was no significant difference between the two groups in aqueous flare and
      cells at any of the postoperative visits. In this study we were unable to
      demonstrate any beneficial effect of subconjunctival betamethasone on damage to
      and recovery of the BAB following cataract surgery in the uncomplicated eye.

PMID- 1390530
TI  - Long-term survival of endothelium following transplantation of corneas stored by
      organ culture.
AB  - This study reports corneal graft survival, endothelial cell changes, and visual
      outcome in 20 patients who received some of the first corneas stored by organ
      culture in the Corneal Transplant Service Eye Bank in Bristol. Mean donor age was
      48 years (SD 15, n = 20) and corneas were stored for an average of 21 days (SD 7,
      n = 20). Preoperative endothelial cell density was 2334 cells/mm2 (SD 235, n =
      18) and this fell by 8% (SD 12) to 2158 cells/mm2 (SD 372) within the first 2
      months following transplantation. In 13 patients, endothelial cell density
      thereafter declined exponentially with a half-life of 41 months (SD 17, n = 12;
      one patient excluded as an outlier). Corneas that suffered rejection episodes
      showed the highest rates of loss of endothelial cells. Endothelial cell loss 4
      years after transplantation was 46% (SD 16, n = 12), which was similar to the
      postoperative decline in cell density reported for corneas stored for far shorter
      periods in McCarey-Kaufman medium at 4 degrees C.

PMID- 1390531
TI  - Assessment of central visual function after successful retinal detachment surgery
      by pattern visual evoked cortical potentials.
AB  - The pattern of visual recovery after successful surgery by pattern visual evoked
      cortical potentials (VECP), visual acuity, colour vision, and critical fusion
      frequency was investigated in 14 eyes with retinal detachment involving the
      macula. The temporal tuning characteristics in the evoked potentials were
      measured as based on the P100 amplitude and the frequency necessary for evoking 0
      mu V amplitude, which was defined as an objective critical fusion frequency by
      extrapolating the curve. Significant improvement in visual acuity and colour
      vision was observed within 2 months postoperatively. A significantly increased
      P100 peak latency became shorter as the postoperative days increased. In general,
      a good correlation was noted between the P100 peak latency and subjectively
      measured visual acuity, colour vision, and critical fusion frequency. The
      objective critical fusion frequency measured by VECP recovered gradually during
      the 6 months after surgery. Functional recovery was not related to the length of
      time the macula was detached before surgery.

PMID- 1390532
TI  - Fibronectin synthesis in subretinal membranes of proliferative vitreoretinopathy.
AB  - In situ hybridisation and immunohistochemical studies were conducted on six
      surgically excised subretinal membranes of proliferative vitreoretinopathy to
      investigate whether displacement of retinal pigment epithelial and glial cells to
      subretinal membranes was associated with fibronectin production by the subretinal
      membrane cells. Fibronectin messenger RNA (mRNA) and fibronectin immunoreactivity
      were observed in some cells in all of the subretinal membranes studied and up to
      30% of the cells in individual specimens showed intense labelling for fibronectin
      mRNA. The results support the concept that the cells in subretinal membranes
      produce fibronectin. Locally produced fibronectin may play a role in subretinal
      membrane cohesion, and displacement of retinal pigment epithelial and glial cells
      from their normal location may induce the cells to manufacture fibronectin.
      Fibronectin production may be more prominent in migrating subretinal cells.

PMID- 1390533
TI  - Prenatal exclusion of Norrie's disease.
AB  - We report on the use of DNA marker probes and linkage analysis to exclude
      Norrie's disease in the male fetus of a high risk carrier. There are no clinical
      markers in females carrying the Norrie's disease gene; thus DNA linkage analysis
      is an essential technique in the management of families 'at-risk' for this severe
      ophthalmic disease. The principles of DNA linkage are discussed.

PMID- 1390534
TI  - Low tension glaucoma--its place in modern glaucoma practice.

PMID- 1390535
TI  - Congenital nystagmus: rebound phenomenon following removal of contact lenses.
AB  - Symptoms resulting from congenital nystagmus can be significantly reduced by
      wearing corneal contact lenses. A 90 minute therapeutic trial with contact lenses
      was performed on a 20-year-old affected patient and produced a beneficial effect.
      Upon removal of the lenses however the patient showed a transient rebound
      phenomenon with oscillopsia lasting about 20 minutes. This phenomenon, although
      it might be expected in theory, has apparently not previously been observed
      either because it is rare or because in most patients it is not clinically
      apparent. The purpose of this report is not to discourage treating patients with
      congenital nystagmus by means of contact lenses, but rather to draw attention to
      the occasional occurrence of such a rebound phenomenon and to discuss its
      theoretical significance.

PMID- 1390536
TI  - Behcet's disease: activated T lymphocytes in retinal perivasculitis.
AB  - A 38-year-old man who died from systemic Behcet's disease had previously suffered
      from severe, recurrent bilateral retinal vasculitis, and anterior uveitis for 10
      years. Immunopathological examination of the eyes postmortem revealed marked
      hyaline thickening of the retinal and optic nerve vessels. The vessels had an
      intramural and perivascular infiltrate of T lymphocytes which stained positively
      for CD4 and IL2 receptor surface markers. Small numbers of cells in the optic
      nerve head, retinal vascular endothelium, and retinal pigment epithelium were HLA
      DR positive.

PMID- 1390537
TI  - Sudden blindness in a child: presenting symptom of a sphenoid sinus mucocele.
AB  - A 10-year-old girl with no nasal or respiratory symptoms developed a headache
      lasting a few hours. The next day she became totally blind in the right eye and
      over 5 days vision in the left eye deteriorated to bare light perception. The
      diagnosis of a sphenoid sinus mucocele was made radiologically and drainage via
      an endonasal sphenoidectomy produced 12 ml of brownish fluid. Endoscopic biopsy
      of the wall confirmed the diagnosis of a mucocele. Steroid treatment was given
      postoperatively, but vision recovered to 6/12 in the left eye only. The
      importance of urgent clinical diagnosis and treatment is stressed.

PMID- 1390538
TI  - Actinomycosis of the orbit.
AB  - Actinomycosis is a very rare cause of orbital abscess usually attributable to
      direct spread from adjacent structures. A case of actinomycosis of the orbit is
      presented, which was treated as orbital pseudotumour for 3 months before
      progression of signs and symptoms, despite high dose steroids, led to the
      diagnosis being reconsidered.

PMID- 1390539
TI  - Phakomatous choristoma of the orbit: a case report.
AB  - We report the case of a 3-month-old infant with a rare phakomatous choristoma of
      the orbit. This lesion is believed to be a congenital neoplasm of lenticular
      anlage. The clinical, radiological, and histopathological findings are presented.

PMID- 1390540
TI  - Broken intraocular lens during cataract surgery.
AB  - A case of planned routine extracapsular cataract extraction is described where
      surgery was complicated peroperatively by fracture of the posterior chamber lens
      implant. The technique of lens implantation is discussed.

PMID- 1390541
TI  - Cowpox virus.

PMID- 1390542
TI  - Segmentation of fluorescence in the retinal microcirculation--is it a valid
      indicator of blood cell flow?

PMID- 1390543
TI  - Periorbital necrobiosis lipoidica.

PMID- 1390545
TI  - Current concepts in pediatric burn care: surgery of severe burns.
AB  - Optimal surgical therapy of severe burns in children has been controversial for a
      long time. A review of the current literature shows that prompt surgical excision
      of necrotic tissue and immediate autografting have become the standard in most
      burn centers. The authors present a concept based on prompt excision of third
      degree burns and discuss the problems of intermediate cover arising in massive
      burns.

PMID- 1390544
TI  - Current concepts in pediatric burn care: general management of severe burns.
AB  - Severe burns and scalds are still frequent. If the burn victim is a child, it
      should ideally be taken care of in a pediatric burn center, where both the burn
      and child-related needs are specifically met. The goals of burn care are to
      preserve life, to preserve function, to limit physical and psychological sequelae
      and to provide social reintegration. The system of burn care essentially consists
      of adequate initial resuscitation followed by early surgery aimed at rapid and
      definitive wound closure. Vigorous nutritional support as well as early
      rehabilitation and continuous psychosocial care are of paramount importance. The
      paper summarizes the essentials of pediatric burn care (burn surgery excluded).

PMID- 1390547
TI  - Current concepts in pediatric burn care: morphology and biology of normal human
      skin and stratified cultures of epidermal cells for wound covering.

PMID- 1390546
TI  - Current concepts in pediatric burn care: artificial skin--its place in the system
      of pediatric burn care.

PMID- 1390548
TI  - Current concepts in pediatric burn care: management of burn wounds with cultured
      epidermal autografts.
AB  - Our experience with CEA is based on 21 patients operated on from 1986 to 1991.
      The areas covered with CEA measured 500 cm2 to 3160 cm2. At one setting no more
      than 40 sheets of 40 cm2 CEA have been transplanted. The take of CEA is over 75%
      when applied to dermis. The same holds true when covering "deepithelialised" skin
      homografts on immunosuppressed patients. Scar formation has not been a problem,
      and the overall results have been good.

PMID- 1390549
TI  - Current concepts in pediatric burn care: the biology of cultured epithelial
      autografts: an eight-year study in pediatric burn patients.
AB  - An 8-year histopathological study of skin regeneration and wound healing in 22
      pediatric patients treated with cultured epithelial autografts (CEA) grafted to
      full-thickness burn wounds excised to muscle fascia is reported. Biopsies of CEA
      have been analyzed by light microscopic, immunohistochemical, morphometric,
      electron microscopic and ultrastructural immunolabelling techniques and compared
      to controls of meshed split-thickness autograft (MSTA) interstices at comparable
      times postgrafting. At transplantation, CEA are undifferentiated and lack both
      granular and cornified cell layers. By 6 days postgrafting, CEA differentiate all
      normal epidermal strata but lack rete ridges. De novo formation of a confluent
      basal lamina and mature hemidesmosomes is complete by about 3 weeks. Anchoring
      fibrils appear sparse and immature (as in MSTA controls) compared to normal skin
      until about 6-12 months. CEA develop rete ridges and a neodermis with normal
      stromal and vascular organization at about 6-12 months, whereas MSTA interstice
      controls do not. At 4-5 years, elastin expression is also observed in the CEA
      neodermis, completing the dermal regeneration process. Normal epidermal
      differentiation is maintained long-term. These long-term results indicate that
      CEA regenerate a stable normal epidermis and are capable of inducing dermal
      regeneration from wound bed connective tissue.

PMID- 1390550
TI  - Critical reflections on the use of human cultured keratinocytes in children with
      burns.
AB  - The authors report on their experience in the use of cultured keratinocytes in
      severely burned children, observed in the Surgical Emergency and Pediatric
      Surgery Department at the Gaslini Institute of Genova. Seventeen cases are
      described, divided into three groups: patients treated exclusively by autografts;
      patients treated both by auto- and allografts; patients treated exclusively by
      allografts. Indications to the various techniques are reported, and the
      advantages and disadvantages of cultured skin are discussed. Some of the most
      likely causes of failure are pointed out, with an update review of the
      literature.

PMID- 1390551
TI  - Acute respiratory distress due to malignant schwannoma. A case report.
AB  - A 13-year-old boy with acute respiratory distress due to a malignant schwannoma
      located in the neck, is reported. This case suggested that malignant schwannoma
      in the neck can lead to airway obstruction.

PMID- 1390552
TI  - Tracheal rupture in a newborn during a complicated delivery. Diagnosis and
      surgical repair.
AB  - Rupture of the trachea is an exceptional obstetrical lesion. The infant reported
      in this paper, at 1 hour of age, developed respiratory distress with
      pneumomediastinum, bilateral pneumothorax and subcutaneous emphysema. This
      resulted from the fact that the trachea had ruptured, within 1 cm of the carina,
      during the difficult delivery. When the child was 23 days old, operation proved
      necessary because extubation was not feasible. The stenotic portion of the
      trachea was resected and continuity restored by end-to-end anastomosis. The
      tracheal lumen at the site of the anastomosis proved normal by bronchoscopic
      examination 4 months after the operation. There is only one similar case in the
      literature. The etiology of this rupture is discussed.

PMID- 1390553
TI  - Air trapping from torsion of a congenital cyst of the lung.
AB  - Report on a case of congenital cyst of the lung which was attached to the pleura
      of the right upper lobe and because of torsion of its pedicle produced air
      trapping and mediastinal shift. Etiology, diagnosis and surgical indications are
      reviewed from the literature. No similar case has been previously reported.

PMID- 1390554
TI  - Esophageal stricture as a complication in Henoch-Schonlein purpura.
AB  - We report on a three-year-old boy with Henoch-Schonlein purpura developing an
      esophageal stenosis during severe clinical course of this disease. There are to
      date no reports on the development of such a complication. The possible
      pathogenesis in relation to stricture formation of ileum and ureter in Henoch
      Schonlein's purpura is discussed.

PMID- 1390555
TI  - Intussusception and duodenal stenosis: an infrequent but expected association.
AB  - Two boys with intussusception, intestinal malrotation and duodenal stenosis are
      reported. Because intussusception is associated with malrotation, which is in
      turn associated with duodenal stenosis, this combination of abnormalities may be
      expected in up to 3% of children with intussusception.

PMID- 1390556
TI  - Lactic acidosis from thiamine deficiency during parenteral nutrition in a two
      year-old boy.
AB  - This is a case report of a two-year-old boy who was operated electively for a
      blind-loop syndrome of the proximal jejunum. Because of the appearance of chylous
      ascites, parenteral nutrition was carried out postoperatively. The boy developed
      a severe uncompensated acidosis and paralytic ileus. Relaparotomy on suspicion of
      ischemic bowel did not explain the cause of the acidosis and ileus.
      Postoperatively, the child's condition worsened, requiring intensive care. The
      drastically elevated lactate levels corroborated the eventually suspected
      diagnosis of a vitamin B1 deficiency syndrome. The administration of thiamine
      within two hours produced correction of the acidosis without further bicarbonate
      therapy. In 24 hours circulation was stabilized. Two months post-operatively the
      boy had completely recovered from the sequelae of his shock event.

PMID- 1390557
TI  - Endorectal pull-through operation for diffuse cavernous hemangiomatosis of the
      sigmoid colon, rectum and anus.
AB  - A 6-year-old girl with diffuse cavernous hemangiomatosis of the sigmoid colon,
      rectum and anus underwent endorectal pull-through operation for sphincter-saving
      resection. Rectal mucosa was resected from 4 cm above peritoneal reflection to
      anal skin margin and the normal sigmoid colon was pulled down through the rectal
      muscular cuff. Ligation of the superior rectal and left internal iliac arteries
      at operation achieved satisfactory control of bleeding. Postoperative manometric
      studies showed almost normal sphincter tone and good response to rectal stimuli
      by balloon inflation. The endorectal pull-through (Soave-Denda procedure) is a
      common procedure for Hirschsprung's disease and the best procedure for the
      sphincter-saving treatment of diffuse cavernous hemangiomatosis of the colon and
      rectum.

PMID- 1390558
TI  - Bilateral intra-scrotal fat necrosis in a child.

PMID- 1390559
TI  - Prevention of maxillofacial trauma.

PMID- 1390560
TI  - Facial balance in cleft lip and palate. I. Normal development and cleft palate.
AB  - A full understanding of balanced facial growth, based on a complete knowledge of
      the anatomy and physiology of the region, is essential if cleft lip and palate is
      to be treated successfully. The cleft abnormality is the cause of
      underdevelopment and subsequent loss of function. Cleft surgery must aim to
      restore normal anatomy and physiology with emphasis on muscle reconstruction of
      the lip and soft palate if normal facial development is to be achieved.

PMID- 1390561
TI  - Facial balance in cleft lip and palate. II. Cleft lip and palate and secondary
      deformities.
AB  - The cleft abnormality is the cause of underdevelopment and subsequent loss of
      function. Primary cleft surgery and surgery to correct the secondary deformities
      of previous non-functional repair should aim to restore normal anatomy and
      physiology, with an emphasis on muscle reconstruction of the lip and soft palate
      if normal facial development is to be encouraged.

PMID- 1390562
TI  - A three dimensional analysis of soft and hard tissue changes following
      bimaxillary orthognathic surgery in skeletal III patients.
AB  - The three dimensional changes in the bone and the ratio of soft tissue to bone
      movement were investigated in a group of 16 Skeletal III patients following
      orthognathic surgery. Computerised tomogram scans were taken for each patient pre
      operatively and 1 year postoperatively. The scans were superimposed, radial
      measurements calculated, and the changes illustrated by two separate colour
      scales. There was no constant pattern of movement in the maxilla or mandible in
      these patients. However, following a Le Fort 1 osteotomy there was commonly a 1:1
      ratio in the midline which increased to 1.25:1 at the alar bases and over the
      canine regions bilaterally. There was also a 1.25:1 ratio or greater over the
      chin and mentalis regions following mandibular set back.

PMID- 1390563
TI  - The conservative management of osteoradionecrosis of the mandible with ultrasound
      therapy.
AB  - A regimen of ultrasound with local debridement and metronidazole has proved to be
      an effective and practicable treatment for osteoradionecrosis, achieving healing
      in 10/21 (48%) cases without the need for surgery or sophisticated technology.
      Nine further patients were successfully treated by covering the preserved
      mandible with a local intra-oral flap. Only 2 patients required mandibular
      resection with reconstruction. An ultrasound programme of 1 watt/cm2, 3 mega Hz.
      pulsed 1:4, 15 min a day for 60 days would seem to be optimum. However, a range
      of dosage needs to be further explored for inducing neovascularity and
      neocellularity in the irradiated tissues.

PMID- 1390565
TI  - Cosmetic extensile exposure of the facial skeleton.
AB  - Professor A. K. Henry coined the term 'extensile exposure'. Three incisions are
      described to expose the facial skeleton. The incisions are placed to best
      cosmetic advantage and provide extensile exposure to fit many of the routine
      procedures undertaken by the oral and maxillofacial surgeon.

PMID- 1390564
TI  - Informed consent in oral and maxillofacial surgery: a study of its efficacy.
AB  - This paper explains the legal principle of informed consent in surgery and
      presents the results of a study of the efficacy of verbal information as part of
      the informed consent process in oral and maxillofacial surgery, using third molar
      surgery as a model. The results showed that patients were most likely to recall
      being warned about pain and swelling and less likely to recall being warned about
      trismus, dysaesthesia of the lip and dysaesthesia of the tongue. The last two are
      complications with important medicolegal implications. It appeared to make no
      difference to their recall if they were given this information on a preadmission
      clinic or on admission. The implications of these findings are discussed.

PMID- 1390566
TI  - Professional qualifications of the membership of the British Association of Oral
      and Maxillofacial Surgeons.
AB  - The medical and higher academic qualifications of the current membership of the
      British Association of Oral and Maxillofacial Surgeons were analyzed. Of the
      total membership, 69.3% possessed a postgraduate dental fellowship, 28.3% held a
      formal medical qualification and 16.5% held a higher academic degree. Half
      (45.9%) of the Fellows (Consultants), one-third (28.1%) of the Members and one
      tenth (10.9%) of the Associate Members were medically qualified. Consultants in
      NHS positions and Members in higher training grades accounted for the majority of
      medically qualified individuals. Higher academic qualifications were held by one
      fifth (20.8%) of Fellows, one-tenth (11.4%) of Members and one-fifth (17.7%) of
      Associate Members. Most of those possessing higher academic qualifications were
      consultants in University appointments, Members not in training and overseas
      Associate Members. A dental basis for the specialty was upheld by the finding
      that 99.7% of Fellows held a post-graduate dental fellowship. These results are
      discussed in relation to current recommendations for clinical and academic
      training in oral and maxillofacial surgery in the UK.

PMID- 1390567
TI  - Jehovah's Witness: a management dilemma in severe maxillofacial trauma.
AB  - The fundamentalist beliefs of a Jehovah's Witness can create major clinical and
      medicolegal problems when blood or blood products are needed to sustain life. The
      continuing expansion of Jehovah's Witnesses (1/4 million in UK; 4 million
      worldwide) means that encounters with the sect and surgeons in clinically
      critical situations are likely to increase. This paper describes such a case in
      which a 24-year-old male died from maxillofacial injuries because transfusion was
      denied. The special clinical and ethical management criteria are emphasized and
      the legal vulnerability of the clinician is discussed. It is no longer possible
      for clinicians in the UK to act independently in the management of such cases
      without risking censure or loss of indemnity from the employing health authority.

PMID- 1390568
TI  - Cowden's disease: a rare but important manifestation of oral papillomatosis.
AB  - A case of Cowden's disease is reported, and possible differential diagnosis for
      the oral lesions is suggested.

PMID- 1390569
TI  - Diverticular pouch of the buccal mucosa.

PMID- 1390570
TI  - Retrobular haematoma.

PMID- 1390571
TI  - A modified Kloehn bow for cranio-maxillary fixation.

PMID- 1390572
TI  - Compulink information exchange (CIX)

PMID- 1390573
TI  - The prevalence of orthodontic treatment need.
AB  - The prevalence of unmet orthodontic treatment need amongst 955 12-year-old
      Sheffield children has been assessed using the Index of Orthodontic Treatment
      Need [I.O.T.N.]. The Index was found to be quick and simple to use, and
      demonstrated very good levels of intra-examiner agreement.

PMID- 1390574
TI  - Shear bond strength of ceramic brackets with chemical or mechanical retention.
AB  - The study was undertaken to measure and compare the shear bond strengths of a
      ceramic bracket with chemical retention, a ceramic bracket with a new type of
      textured base providing mechanical retention, and a metal bracket with foil-mesh
      base. The tests were performed on 51 extracted human premolars which were
      randomly divided into three equally large groups (n = 17)--one group for each
      type of bracket. After debonding, the site of failure was noted and the enamel
      surface inspected with scanning electron microscopy. The ceramic bracket with
      chemical retention exhibited significantly higher bond strength than the
      corresponding bracket with textured base. In comparison with the metal bracket
      significantly higher bond strengths were recorded for both types of ceramic
      brackets. The ceramic bracket with mechanical retention and the metal bracket
      were comparable as regards the site of bond failure. In some cases the chemical
      bond provided very high values of bond strength. Enamel failure were recorded in
      three teeth which had been bonded with this type of ceramic bracket.

PMID- 1390575
TI  - Decalcification during orthodontic treatment with fixed appliances--an overview.

PMID- 1390576
TI  - An investigation into the effect of a fluoride releasing adhesive on the
      prevalence of enamel surface changes associated with directly bonded orthodontic
      attachments.
AB  - Despite careful patient selection, decalcification still remains a problem during
      fixed orthodontic treatment. The advantages of a method of delivering fluoride to
      the area of the tooth most at risk, which does not rely on patient compliance,
      makes a fluoride releasing bonding adhesive desirable. The aims of this study
      were to investigate the potential of a fluoride releasing bonding material for
      preventing decalcification and to monitor its efficacy at retaining orthodontic
      brackets. In order to carry out the first part of the study it was necessary to
      devise a reproducible and sensitive method of recording the extent and severity
      of any decalcification. A photographic technique which fulfils these criteria is
      described.

PMID- 1390577
TI  - The performance of first molar orthodontic bands cemented with glass ionomer
      cement--a retrospective analysis.
AB  - Various factors influencing the survival time of orthodontic bands cemented to
      first permanent molars with glass ionomer cement (KETAC-CEM, Espe) have been
      investigated. Data on 513 patients with 1424 first molar bands who completed
      orthodontic treatment between 1985 and 1989 inclusive were analysed. Performance
      of bands cemented to first permanent molars varied according to the operator, age
      of the patient and treatment mechanics, but not according to the sex of the
      patient or quadrant in which the band was fitted.

PMID- 1390578
TI  - Bioprogressive brackets and pentamorphic arches.
AB  - The use of high torque values with no tip in preadjusted incisor brackets in the
      Bioprogressive system, in conjunction with narrow anterior rectangular archwires
      may produce crown spacing, root crowding and upright central incisors. The
      solution to these problems would seem either to reduce the time spent in
      rectangular wires or to change to a bracket with reduced torque, together with
      appropriate second order compensations in the archwire or the bracket.

PMID- 1390579
TI  - Storage of orthodontic study models in hospital units in the U.K.
AB  - Orthodontic study models form an essential part of the dental records of patients
      undergoing diagnosis and treatment. In order to ascertain the problems
      encountered by hospital orthodontic units in the utilization and storage of study
      models, a questionnaire was circulated in February 1991 to members of the
      Consultant Orthodontists Group. All respondents took pretreatment study models,
      while 9 per cent took their final study models at some time other than the end of
      active treatment; 85.5 per cent of respondents stored their study models in their
      units, but most were beginning to experience difficulties in this regard. There
      was a wide range for storage times, and only 10 per cent of employing authorities
      had a stated policy on the storage of study models. There was a highly
      significant difference (P much less than 0.001) between the time that models are
      stored at present, and the desired storage times. Most respondents appeared to be
      rather uncertain about the precise medico-legal requirements concerning model
      storage. The implications for audit and medico-legal matters are discussed in the
      light of these findings.

PMID- 1390581
TI  - The Erasmus Project.

PMID- 1390580
TI  - Methods of debonding ceramic brackets.
AB  - The problem of debonding ceramic brackets is still one which concerns the
      orthodontist. It is advisable to use the manufacturers recommended method of
      debonding each particular type of bracket. The risks of using such brackets need
      to be carefully assessed against the benefits. Risks can be minimized by
      carefully assessing the patient and the dentition, avoiding heavily restored
      teeth with pre-existing enamel cracks. It would seem wise to obtain an informed
      consent from the patient having out-lined the potential problems.

PMID- 1390582
TI  - Three years postgraduate programme in orthodontics. Final report Erasmus Project.

PMID- 1390583
TI  - Initiation and regulation of tissue factor-dependent blood coagulation.

PMID- 1390584
TI  - Lipoproteins enhance fibronectin binding to adherent cells.
AB  - We have identified very low density (VLDL) and low density (LDL) lipoproteins as
      blood plasma components that enhance the binding and deposition of fibronectin
      into the extracellular matrices of cultured MG-63 osteosarcoma cells and human
      fibroblasts. The lipoproteins increased the binding and deposition of iodinated
      fibronectin by MG-63 cells threefold over control levels. LDL also increased the
      deposition of multimeric fibronectin into extracellular matrix as assessed by gel
      electrophoresis and fluorescence microscopy. High density lipoprotein (HDL) and
      the d > 1.21 g/ml nonlipoprotein fraction had less activity. Enhancement of
      binding of fibronectin was observed within 15 minutes, when binding was largely
      reversible. LDL also increased the binding of a fragment containing the 70-kd
      amino-terminal region of fibronectin that is primarily responsible for the
      reversible binding of fibronectin to cell layers. LDL had to be present
      simultaneously with radiolabeled fibronectin to exert an effect on fibronectin
      binding. LDL enhanced fibronectin binding equally well to normal skin fibroblasts
      and to familial hypercholesterolemic fibroblasts lacking the LDL receptor.
      Acetylation of LDL, performed to block its interaction with the LDL receptor, did
      not diminish the enhancement of fibronectin binding to MG-63 cells. These results
      indicate that LDL and VLDL interact with fibronectin to potentiate binding to
      monolayer cells through a pathway that does not involve the LDL receptor.

PMID- 1390585
TI  - Redirected targeting of LDL to human monocyte Fc gamma receptors with bispecific
      antibodies.
AB  - Recent studies indicate that low density lipoprotein (LDL)-immune complexes
      consisting of anti-LDL antibodies bound to LDL may contribute to macrophage foam
      cell development by uptake through immunoglobulin G (IgG) Fc receptors. As human
      mononuclear phagocytes possess three structurally and functionally distinct
      classes of IgG Fc receptors, we developed a system whereby the effects of LDL
      immune complexes could be studied with respect to each type of IgG Fc receptor.
      Novel bispecific antibodies consisting of anti-Fc gamma receptor antibodies
      linked to anti-LDL antibodies were used to prepare bispecific LDL-immune
      complexes for targeting to specific Fc gamma receptors. In this report, the
      effects of bispecific LDL-immune complexes directed to Fc gamma receptor types I,
      II, and III were studied primarily with monocytes and were compared with the
      effects of similarly prepared bispecific complexes that targeted LDL to human
      leukocyte antigen (HLA) class I antigens. Each type of bispecific antibody was
      effective in targeting 125I-LDL to its respective site on the cell surface. Using
      fluorophore-labeled LDL and flow cytometry, bispecific complexes directed to Fc
      gamma receptor types I or II but not to HLA class I antigens caused a two- to
      sevenfold increase in cell-associated fluorescence relative to control cells
      treated with LDL in the absence of bispecific antibody. Uptake occurred in the
      presence of excess unlabeled LDL, acetylated LDL, and antioxidants. That the
      bispecific complexes triggered metabolic uptake was supported by studies of
      kinetics and temperature dependence. Using 125I-labeled complexes, metabolic
      degradation of LDL was demonstrated in association with each of the three types
      of Fc gamma receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390586
TI  - Beta-VLDL-induced cholesterol ester deposition in macrophages may be regulated by
      neutral cholesterol esterase activity.
AB  - We examined the role of enzyme activities involved in cholesterol ester
      metabolism in the accumulation of cholesterol ester in macrophages. When
      [3H]cholesterol linoleate-beta-very low density lipoproteins (beta-VLDLs) were
      incubated with rat resident peritoneal macrophages (RPMs), thioglycolate-elicited
      macrophages (TEMs), or alveolar macrophages (AMs), cholesterol ester accumulation
      was the greatest in TEMs and the least in AMs. The uptake of [3H]cholesterol
      linoleate-beta-VLDL into AMs was four times that into RPMs, and the uptake into
      TEMs was twice that into RPMs. The [3H]cholesterol released from [3H]cholesterol
      linoleate-beta-VLDL-loaded AMs was five times higher than from TEMs and RPMs,
      whereas those from RPMs and TEMs were almost the same. In studies using cell
      homogenates, the acid cholesterol esterase activity in AMs was 1.7 times that in
      TEMs and six times that in RPMs. The acyl-coenzyme A:cholesterol acyltransferase
      (ACAT) activities in AMs and TEMs were similar but were higher than that in RPMs.
      The neutral cholesterol esterase activity was seven times higher in AMs than in
      RPMs and TEMs. In the study using intact cells, the hydrolysis of loaded
      [3H]cholesterol linoleate-beta-VLDL in the presence of the ACAT inhibitor
      CL277,082 and the cholesterol [14C]oleate synthesis from [14C]oleate were
      enhanced in AMs about twofold compared with RPMs and TEMs. The reduction of de
      novo synthesized cholesterol [14C]oleate in the presence of CL277,082 was
      enhanced in AMs four times compared with TEMs or RPMs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1390587
TI  - Effect of marine lipids on cholesteryl ester transfer and lipoprotein composition
      in patients with hypercholesterolemia.
AB  - While the effects of omega-3 (n-3) fatty acids present in marine lipids on plasma
      lipoprotein levels have been intensively studied, less is known about their
      impact on reverse cholesterol transport. For this reason, for a 3-month period we
      studied the effects of the administration of n-3 fatty acids (6 g/day) as a
      dietary supplement on cholesteryl ester transfer (CET), a key step in this
      process, and lipoprotein composition in 12 outpatients with genetically
      heterogeneous forms of hypercholesterolemia. Before treatment, CET in
      hypercholesterolemic patients, estimated as the mass of cholesteryl ester (CE)
      transferred from high density lipoprotein (HDL) to very low density lipoprotein
      (VLDL) plus low density lipoprotein (LDL), was markedly accelerated, peaking
      after only 1-2 hours of incubation of whole plasma; this response differed
      significantly (p < 0.001) from the initial delayed curvilinear response of
      control subjects. Consistent with the accelerated CET occurring in vivo, their
      triglyceride to esterified cholesterol core lipid ratio before treatment was
      reduced in the intact VLDL fraction and VLDL1 but not in VLDL2 or VLDL3 and was
      reciprocally increased in HDL. In addition, the free (unesterified) cholesterol
      to lecithin ratio of VLDL1 was abnormally increased. Recombination experiments
      performed with individual lipoprotein fractions revealed that accelerated CET was
      specifically associated with the VLDL1 subfraction and not LDL, HDL, and
      cholesteryl ester transfer protein (CETP), although pretreatment levels of CETP
      were significantly increased (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390588
TI  - Reevaluation of regression of coronary arteriosclerotic lesions in repeat
      spawning steelhead trout.
AB  - At spawning, migratory salmonids have an extensive accumulation of coronary
      arteriosclerotic lesions. Nevertheless, when steelhead trout (Oncorhynchus
      mykiss) return to the ocean after spawning, an unusual phenomenon has been
      reported, namely, that these lesions have regressed naturally and almost
      completely (R.L. Van Citters and N.W. Watson, Science 1968; 159:105-107). In
      contrast to this earlier finding, we present data that show a high prevalence and
      severity of coronary lesions in 1) wild, repeat-spawning steelhead trout that
      were caught at high sea and 2) wild and cultured steelhead trout that had been
      held in sea pens for up to 1 year after maturation. Therefore, we refute the idea
      of natural lesion regression in steelhead trout. Coronary lesions in salmonids
      are characteristically lipid free despite the fact that there are high plasma
      levels of both total cholesterol and low density lipoproteins. This situation
      contrasts with the characteristic lipid deposition during lesion development in
      mammals. We therefore suggest that attention should be directed to explaining why
      coronary lesions accumulate despite very high dietary levels of omega-3
      polyunsaturated fatty acids in the diets and tissues of these fish.

PMID- 1390589
TI  - Familial combined hyperlipidemia and abnormal lipoprotein lipase.
AB  - A previous study reported that heterozygotes for lipoprotein lipase (LPL)
      deficiency have reduced LPL, the lipoprotein pattern classified as familial
      combined hyperlipidemia (FCHL), elevated apolipoprotein (apo) B levels, and
      reduced high density lipoprotein (HDL) levels. These findings suggest that
      subjects with reduced LPL may form one subset of the FCHL population. The purpose
      of the present study is to determine whether a subset of patients with FCHL have
      reduced LPL. Three patient populations with FCHL were studied: 1) subjects with
      the diagnosis of FCHL (n = 9) established by previous family studies, 2) clinic
      patients with a tentative diagnosis of FCHL (n = 14), and 3) subjects undergoing
      angiography who had coronary artery disease (CAD) and a diagnosis of FCHL by
      family study (n = 33). Two of nine subjects with the established diagnosis of
      FCHL, five of the 14 FCHL clinic patients, and 13 of the 33 CAD subjects with
      FCHL had reduced LPL activity in the same range as do individuals who are
      obligate heterozygotes for LPL deficiency. Subjects with FCHL and reduced LPL had
      higher plasma triglyceride (p < 0.01) and lower HDL cholesterol (p < 0.025)
      levels than did the subjects with FCHL and normal LPL levels (327 +/- 201 versus
      210 +/- 122 mg/dl [mean +/- SD] and 36 +/- 7 versus 44 +/- 13 mg/dl,
      respectively). Thus, in all three groups of patients with apparent FCHL, 20 of 56
      subjects (36%) had reduced LPL, suggesting that one subset of the FCHL population
      may be identified by an abnormality in LPL activity that is associated with
      lipoprotein abnormalities.

PMID- 1390590
TI  - Delayed clearance of postprandial chylomicrons and their remnants in the
      hypoalphalipoproteinemia and mild hypertriglyceridemia syndrome.
AB  - Hypoalphalipoproteinemia (HPAL) with mild hypertriglyceridemia (HTG) is
      associated with increased coronary artery disease (CAD) risk. The aim of this
      study was to examine the metabolism of postprandial lipoproteins in HPAL/HTG
      subjects (n = 21). They had a fasting plasma high density lipoprotein (HDL)
      cholesterol level < 0.9 mmol/l, a triglycerides (TG) level of 2.0-7.1 mmol/l, and
      a normal low density lipoprotein (LDL) cholesterol level (< 3.7 mmol/l). They
      were either homozygous for apoprotein E3 (n = 13) or heterozygous for apoprotein
      E4 (n = 5) or E2 (n = 3). After ingestion of a vitamin A fat load, plasma and
      chylomicron (CM) retinyl palmitate (RP) response (areas under curves) was three
      times and non-CM RP response 2.5 times greater than in normolipidemic control
      subjects (n = 13). There was close correlation between fasting plasma TG level
      and postprandial RP response in HPAL/HTG subjects (plasma, r = 0.87; CM, r =
      0.89; and non-CM, r = 0.84). In control subjects this correlation was present for
      plasma RP (r = 0.80) and CM RP (r = 0.61) but not for non-CM RP (r = 0.53). In
      contrast, postprandial RP response was not correlated with fasting plasma HDL
      cholesterol levels for both groups. There was also no correlation between fasting
      TG and fasting HDL cholesterol. Postheparin lipoprotein lipase and hepatic lipase
      activities were slightly higher in HPAL/HTG subjects. The pattern of postprandial
      change in HDL composition was similar to that in control subjects. These data
      indicate enhanced postprandial lipemia in the HPAL/HTG syndrome, and this may
      account for their increased CAD risk.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390591
TI  - Modulation of fibrinolytic response to venous occlusion in humans by a
      combination of low-dose aspirin and n-3 polyunsaturated fatty acids.
AB  - Aspirin at high but not at low doses reduces the fibrinolytic response to venous
      occlusion. Inhibition of vascular prostacyclin synthesis could be involved in
      this effect. Fish oil supplementation may redirect prostanoid metabolism toward
      an overall "antithrombotic" condition but with controversial effects on
      prostacyclin formation. In this study we investigated the effect of low-dose
      aspirin together with n-3 polyunsaturated fatty acid (PUFA) supplementation on
      the fibrinolytic response to venous occlusion. Following a double-blind,
      randomized, crossover design, six healthy volunteers (three men and three women,
      24-37 years old) were given for 29 days 5.3 g eicosapentaenoic and
      docosahexaenoic acids or a corresponding dose of n-6 PUFAs as control; aspirin
      (40 mg/day) was then added for an additional 14 days. A 2-month washout period
      was allowed before the crossover. Blood was collected before and after venous
      stasis on days 0, 29, and 43 of each test period. A combination of aspirin with n
      3 PUFAs reduced the fibrinolytic response to venous occlusion in all subjects,
      the mean value of fibrinolytic activity after stasis being 240 +/- 40 mm2, a
      value significantly lower than at baseline (366 +/- 51 mm2, mean +/- SEM, p <
      0.05). Similarly, the tissue-type plasminogen activator (t-PA) antigen level was
      lower in the aspirin + PUFA-treated group. Plasminogen activator inhibitor
      activity before stasis was enhanced by n-3 PUFA supplementation (from 7.5 +/- 2
      to 14.8 +/- 3 IU/ml, p < 0.05), an effect not affected by aspirin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390592
TI  - Effect of atherosclerosis on responses of the perfused rabbit carotid artery to
      human platelets.
AB  - Vascular responses to intraluminal and abluminal activation of human platelets
      were examined in carotid arteries from normal and atherosclerotic rabbits. The
      carotid artery was perfused in vitro, platelets were activated with thrombin (0.1
      unit/ml), and changes in diameter were measured. In vessels from normal animals,
      intraluminal activation of platelets produced dilatation of preconstricted
      arteries. The dilator response was attenuated by N omega-nitro-L-arginine (10(-5)
      M), an inhibitor of synthesis of endothelium-derived relaxing factor-nitric oxide
      (EDRF-NO), and augmented by LY53,857 (10(-5) M), a 5-HT2-serotonergic antagonist.
      Abluminal activation of platelets produced modest constriction in quiescent
      arteries, which was inhibited by LY53,857. Intraluminal but not abluminal ADP
      produced pronounced dilatation of preconstricted arteries. In vessels from
      atherosclerotic animals, endothelium-dependent dilatation to intraluminal
      activation of platelets and to ADP was impaired and dilator responses to sodium
      nitroprusside were normal. These experiments indicate that 1) intraluminal
      activation of human platelets produces endothelium-dependent dilatation in
      perfused carotid arteries, whereas abluminal activation of human platelets
      produces vasoconstriction, which is mediated primarily by serotonin, and 2)
      atherosclerosis markedly impairs vasodilator responses to activation of human
      platelets, probably because vasodilatation to ADP released from platelets is
      impaired.

PMID- 1390593
TI  - Apo(a) isoforms predict risk for coronary heart disease. A study in six
      populations.
AB  - Elevated concentrations of lipoprotein(a) (Lp[a]) in plasma are associated with
      premature coronary heart disease (CHD). Lp(a) levels are largely determined by
      alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other
      genetic and environmental factors as well as diseases also affect plasma Lp(a)
      concentrations. It is therefore unclear whether Lp(a) is a primary genetic risk
      factor or whether Lp(a) levels are elevated secondary to disease in CHD patients.
      We have analyzed apo(a) phenotypes that represent a stable genetic trait in
      subjects with CHD and control subjects from different populations representing a
      variety of ethnic groups (Tyrol, Germany, Wales, Israel, Singapore Chinese, and
      Singapore Indian). Despite differences in sampling design and disease definition
      in this multipopulation case-control study, those apo(a) isoforms associated with
      high Lp(a) plasma concentrations (B, S1, and S2) were more frequent in the CHD
      patients in each ethnic group. These differences were significant in three of the
      studied populations and highly significant (p < 0.001) in the pooled (total)
      group. Lp(a) concentrations were also measured in all groups except Germans and
      were found to be consistently higher in cases than in control subjects in each
      ethnic group. For all but one population (Israeli) the differences were
      significant. The effects of the apo(a) size polymorphism on Lp(a) levels were
      similar in CHD patients and control subjects from different populations. The data
      demonstrate that alleles at the apo(a) locus determine the risk for CHD through
      their effects on Lp(a) concentrations across multiple populations with large
      differences in CHD frequency and risk factor profiles.

PMID- 1390595
TI  - A wider view of nutrition.

PMID- 1390594
TI  - Quantification of atherosclerotic plaque composition in cholesterol-fed rabbits
      with 50-MHz acoustic microscopy.
AB  - To determine whether high-frequency ultrasound could distinguish normal from
      pathological vascular structure and to elucidate the determinants of ultrasonic
      backscatter in different layers of normal and atherosclerotic arteries, high
      resolution acoustic microscopy at 50 MHz was used to characterize aortic plaque
      in six New Zealand White rabbits fed a 2% cholesterol diet for 3.5 months. Four
      rabbits were fed a standard diet for 3.5 months to provide normal control data.
      Segments of aortas were excised, fixed in formalin, opened longitudinally, and
      mounted flat for insonification. For each specimen, backscattered radio frequency
      (rf) data were acquired from 30 to 100 independent sites separated by 500
      microns. Portions of rf data were gated from discrete layers of the vessel wall
      for computation of integrated backscatter. Results of histological and
      immunocytochemical analyses of vessel wall thickness and composition were
      compared with those of ultrasonic analysis. Normal aortas manifested prominent
      but homogeneous backscatter (average integrated backscatter, -28.5 +/- 2.9 dB)
      throughout the vessel wall, with no clear distinction between intimal and medial
      layers. The atherosclerotic aortas manifested substantially reduced integrated
      backscatter from the thickened intima (-47.5 +/- 3.2 dB, p < 0.0001) but
      relatively normal integrated backscatter from the media (-31.2 +/- 1.6 dB; p = NS
      versus normal aortas). The thickness of the media for both normal and
      atherosclerotic rabbits was approximately 300 microns. Histological
      characteristics of atherosclerotic aortas confirmed the presence of substantial
      intimal thickening, with prominent foam cell and lipid infiltration abutting a
      more normal medial layer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390596
TI  - True protein digestibility and amounts of endogenous protein measured with the
      15N-dilution technique in piglets fed on peas (Pisum sativum) and common beans
      (Phaseolus vulgaris).
AB  - The faecal and ileal true protein digestibilities of the raw pea (Pisum sativum)
      varieties finale and frijaune and the ileal true protein digestibility of steam
      processed common beans (Phaseolus vulgaris) were measured in piglets using the
      15N-dilution technique. The faecal true protein digestibility of both pea
      varieties was about 97. The ileal true protein digestibility was between 93 and
      95, indicating that the pea protein is almost completely enzymically digested in
      the small intestine. The faecal apparent protein digestibility was 85 for both
      varieties while at the ileal level it was 79 and 74 respectively. The lower ileal
      apparent protein digestibility of peas can be attributed completely to the
      excretion of endogenous protein. The ileal apparent protein digestibility of
      toasted common beans was about zero (-4); the ileal true protein digestibility
      was about 66. This indicates that the protein of the common bean, although
      toasted, was highly resistant to enzymic digestion. It was calculated that per kg
      ingested bean protein, 340 g undigested bean protein and 700 g endogenous protein
      passed the terminal ileum. The results of the present study explain why in
      previous experiments a strongly reduced weight gain and even weight loss was
      observed in piglets fed on raw and toasted common beans.

PMID- 1390598
TI  - Splanchnic fluxes of amino acids after duodenal infusion of carbohydrate
      solutions containing free amino acids or oligopeptides in the non-anaesthetized
      pig.
AB  - Seven non-anaesthetized pigs (mean body-weight 64.6 kg) were used to study the
      intestinal absorption and hepatic metabolism of glucose and amino acids (AA)
      using carbohydrate solutions (maltose dextrin; 440 g/2 I), containing 110 g of
      either an enzymic milk-protein hydrolysate (PEP) with a large percentage of small
      peptides (about 50% with less than five AA residues) and very few free AA (8%) or
      a mixture of free AA (AAL) with an identical pattern, infused intraduodenally.
      Each pig was previously fitted under anaesthesia with electromagnetic flow probes
      around the portal vein and the hepatic artery, and with permanent catheters in
      the portal vein, carotid artery, one hepatic vein and the duodenum. Each solution
      was infused for 1 h after a fasting period (18 h) and each pig received both
      solutions at 8 d intervals. The observation period lasted 8 h. For most AA (his,
      lys, phe, thr, arg, tyr, pro) the absorption rate after infusion of PEP was
      significantly higher than after that of AAL during the 1st hour, but the
      differences quickly disappeared. After 8 h, the only differences concerned his
      and tyr (PEP > AAL) and met, glu and asp (AAL > PEP). There was a large uptake of
      blood AA by gut-wall cells, higher after AAL infusion than after PEP infusion,
      particularly for branched-chain AA (BCAA). The absorption of ammonia-nitrogen
      after both infusions was equivalent to two-thirds of urea-N passing from blood to
      intestinal tissues and lumen. Glucose absorbed within 8 h represented only 76%
      (PEP) or 69% (AAL) of the infused amounts. The cumulative hepatic total AA (TAA)
      uptake increased from 13 to 27% of the infused amounts between the 1st and the
      8th hour after PEP infusion, and from 8 to 31% after AAL infusion. Most essential
      AA were largely taken up by the liver, with the exception of met (PEP) and thr
      and of BCAA, which were poorly retained for both solutions; there was a high
      uptake of ala and gly, and a release of asp, glu, and gln. Urea-N released by the
      liver within 8 h was equivalent to 23-25% absorbed amino-N and to around 1.5
      times ammonia-N taken up by the liver within 8 h. Glucose was highly taken up by
      the liver during the first hours then released, the total uptake within 8 h
      representing about half the absorbed amount.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1390599
TI  - Valine oxidation: the synthesis and evaluation of L-[3-3H]valine as a tracer in
      vivo.
AB  - The suitability of L-[3-3H]valine for measuring valine oxidation was studied by
      comparing its oxidation rate with that of L-[1-14C]valine in rats and pigs. L-[3
      3H]valine was synthesized by removal of the tritium on carbon-2 of L-[2,3
      3H]valine by acetylation. The acetyl group was removed enzymatically using pig
      renal acylase 1 (EC 3.5.1.14) and the product was purified by ion-exchange and
      paper chromatography. For the first rat experiment L-[3-3H]valine was synthesized
      in our laboratory; for the subsequent experiments it was produced by Amersham
      International plc. In the first experiment in rats the two tracers were given by
      injection and 14CO2 was collected for 2 h. The oxidation of tritiated valine was
      significantly higher than that of L-[1-14C]valine. In a second experiment there
      was no difference. This was probably due to the higher purity of the labelled
      valine which, for the second experiment, was shown by nuclear magnetic resonance
      to contain only one tritium atom. In a study with pigs in which the two tracers
      were given by continuous infusion there was no significant difference between
      them in flux or oxidation. The results of this experiment were used to evaluate a
      model to estimate amino acid requirements. With pigs given a methionine-limiting
      diet a reduction in methionine intake, by reducing protein accretion, increased
      valine oxidation by the same proportion.

PMID- 1390597
TI  - Diet among oil-workers on off-shore oil installations in the Norwegian sector of
      the North Sea.
AB  - Dietary studies based on 24 h recalls were carried out on four oil installations
      in the Norwegian sector of the North Sea. Two hundred and three persons were
      interviewed about what they had eaten the previous 24 h. Food purchased for the
      installations in the previous 5 months was recorded. Results based on 24 h
      recalls showed that average daily intake of energy was 12.2 MJ of which 17% came
      from protein, 44% from fat and 39% from carbohydrate, including 8% from sugar.
      Meat, vegetables, fresh fruits, seafood (shellfish), french fries, eggs, cream
      and ice-cream were important components of the diet, while bread, fish and
      cereals played a minor role. Average daily intake (mg) of nutrients were: calcium
      1244, iron 15, vitamin A 1049 micrograms, vitamin D 4.1 micrograms, thiamin 1.6,
      riboflavin 2.2, nicotinic acid 22, ascorbic acid 143. Dietary fibre intake,
      estimated as unavailable carbohydrate, was on average 19 g, and the average daily
      intake of cholesterol was 755 mg. Intakes were compared with the Norwegian
      recommended dietary allowance. Most of the employees chose a diet which when
      eaten over a longer period of time may contribute to the development of coronary
      heart diseases (CHD) and thereby increase the morbidity and mortality from CHD in
      the oil industry.

PMID- 1390600
TI  - Some determinants of postprandial lipaemia in Nigerian diabetic and non-diabetic
      subjects.
AB  - The efficiency of clearance of plasma triacylglycerols (TAG) after fatty meals in
      non-diabetic Caucasian subjects is believed to determine the plasma level of high
      density-lipoproteins-cholesterol (HDL-C). It is unknown if this observation holds
      in diabetic subjects and in other racial groups. In assessing the factors that
      determine TAG responses to acute fat loading in a tropical African population
      with a low prevalence of atherosclerotic disease, twenty (nine obese) non-insulin
      dependent diabetic (NIDDM) patients with optimal glycaemic control and twelve
      (six obese) age-matched non-diabetic subjects were given meals containing 50 g
      fat (in butter) and 75 g carbohydrate (in white bread) over 15 min in the morning
      after a 12 h overnight fast. The fasting plasma levels of glucose, TAG, total
      cholesterol (total-C), HDL-C, low-density-lipoprotein-cholesterol, insulin and
      glycosylated haemoglobin (HBAlc) were estimated; glucose and TAG levels were also
      measured postprandially for 8 h at 2 h intervals. Postprandial lipaemia was
      consistently higher in the diabetic patients (about 50-100% more than values
      obtained in the non-diabetic subjects, even when corrected for differences in
      body mass) and correlated positively with age and postprandial glycaemia. This
      defect in TAG clearance was even worse (by about 50%) when glucose tolerance
      became further impaired after ten of the diabetic patients stopped oral
      hypoglycaemic treatment for 1 week and the fat-tolerance test was repeated. In
      the obese non-diabetic subjects, but not those of normal weight, there were
      significant negative relationships between the postprandial lipaemia and fasting
      plasma levels of HDL-C and HDL-C: total-C ratio, as reported in Caucasians. It is
      concluded that age and the ambient glucose concentration appear to be the
      important determinants of the efficiency of TAG clearance in diabetic subjects.
      This accords with clinical observations of increased atherogenic liability with
      increasing age and poorer glycaemic control. The determinants in non-diabetic
      subjects were less defined, indicating that postprandial lipaemia might be
      influenced by various factors (obesity as shown here) in different subsets of
      individuals.

PMID- 1390601
TI  - The influence of a fish oil high in docosahexaenoic acid on plasma lipoprotein
      and vitamin E concentrations and haemostatic function in healthy male volunteers.
AB  - Nine healthy male subjects consumed a daily fish oil supplement providing 2.1 g
      docosahexaenoic acid (22:6 n-3; DHA) and 0.8 g eicosapentaenoic acid (20:5 n-3;
      EPA) for 6 weeks. The proportion of EPA and DHA in plasma, erythrocytes,
      leucocytes and platelet phospholipids was increased by the supplement. Plasma
      concentration of triacylglycerol and very-low-density-lipoprotein-cholesterol
      were lowered and those of high-density-lipoprotein (HDL)- and HDL2-cholesterol
      and apoprotein B were increased. Platelet aggregation and thromboxane B2
      production induced by collagen were partially inhibited. Both systolic and
      diastolic blood pressure fell during treatment and rose following withdrawal of
      the supplement. Statistically significant reductions in erythrocyte counts,
      packed cell volume and haemoglobin and increases in total leucocyte and monocyte
      counts occurred with the supplement. Plasma alpha-tocopherol concentrations fell
      below the normal range during the period of supplementation. It is suggested that
      future studies consider components other than EPA in fish oil. Further studies
      are needed to investigate the extent to which fish oil increases the requirement
      for antioxidant nutrients.

PMID- 1390602
TI  - Adaptation of biliary response to dietary olive oil and sunflower-seed oil in
      dogs.
AB  - The effects of adaptation to dietary fat of different degrees of unsaturation
      (olive oil and sunflower oil) on bile secretion were studied in dogs at rest and
      after food intake. The animals were prepared with a bidirectional biliary cannula
      and a duodenal cannula to provide bile return. The two experimental groups were
      fed on diets containing 150 g fat/kg in the form of either olive oil (O) or
      sunflower-seed oil (S). The flow-rate under resting conditions and the patterns
      of response to food were similar in both experimental groups, although
      postprandial hypersection were significantly greater in volume and more prolonged
      in group O. No appreciable differences in concentration and output of biliary
      cholesterol or phospholipids were noted between the two groups. In contrast, the
      concentration and output of bile acids differed significantly both at rest and
      after food: concentration and output of bile acids were greater at rest in group
      S. However, after food intake, these responses were increased only in group O.
      The results suggest that the type of dietary fat affects biliary response to
      food, probably through differences in the contribution of the gall bladder in the
      two experimental groups.

PMID- 1390603
TI  - Effect of dietary fatty acid composition on inositol-, choline- and ethanolamine
      phospholipids of mammary tissue and erythrocytes in the rat.
AB  - The present study investigated the effect of feeding maize-oil, olive-oil and
      fish-oil diets, from weaning to adulthood, on rat mammary tissue and erythrocyte
      phospholipid fatty acid compositions. Effects of diet on the relative proportions
      of membrane phospholipids in the two tissues were also investigated. Mammary
      tissue phosphatidylinositol (PI) fatty acids were unaltered by diet, but
      differences in phosphatidylethanolamine (PE) and, to a lesser extent,
      phosphatidylcholine (PC) fractions were found between animals fed on different
      diets from weaning. Differences observed were those expected from the dietary
      fatty acids fed; n-6 fatty acids were found in greatest amounts in maize-oil-fed
      rats, n-9 in olive-oil-fed rats, and n-3 in fish-oil-fed rats. In erythrocytes
      the relative susceptibilities of the individual phospholipids to dietary
      modification were: PE > PC > PI, but enrichment with n-9 and n-3 fatty acids was
      not observed in olive-oil- and fish-oil-fed animals and in PC and PE
      significantly greater amounts of saturated fatty acids were found when animals
      fed on olive oil or fish oil were compared with maize-oil-fed animals. The
      polyunsaturated:saturated fatty acid ratios of PE and PC fractions were
      significantly lower in olive-oil- and fish-oil-fed animals. No differences in the
      relative proportions of phospholipid classes were found between the three dietary
      groups. It is suggested that differences in erythrocyte fatty acid composition
      may reflect dietary-induced changes in membrane cholesterol content and may form
      part of a homoeostatic response the aim of which is to maintain normal
      erythrocyte membrane fluidity. The resistance of mammary tissue PI fatty acids to
      dietary modification suggests that alteration of PI fatty acids is unlikely to
      underlie effects of dietary fat on mammary tumour incidence rates.

PMID- 1390604
TI  - Nutritional implications of L-arabinose in pigs.
AB  - The pentose sugar L-arabinose is one of the most abundant components released by
      complete hydrolysis of non-starch polysaccharides of feed ingredients of
      vegetable origin. Two studies were conducted to investigate the apparent ileal
      digestibility and urinary excretion of L-arabinose at dietary inclusion levels of
      50 and 100 g/kg, and 25, 50, 75 and 100 g/kg respectively, in pigs. As a
      reference, D-glucose was included in the studies. Water intake, ileal flow of
      volatile fatty acids and ileal and faecal digestibilities of dietary nutrients in
      pigs fed on the different diets were also examined. Castrated pigs were prepared
      with a post-valvular T-caecum cannula to measure ileal digestibility. Faecal
      digestibility was measured in non-cannulated pigs. Apparent ileal digestibility
      of L-arabinose was found to be approximately 70%. The presence of L-arabinose in
      the diet increased ileal flow of volatile fatty acids and lactic acid, suggesting
      the occurrence of microbial degradation of L-arabinose in the pig small
      intestine. L-arabinose was partly excreted in the urine. The extent of this
      urinary excretion as a percentage of intake increased linearly (P < 0.01) as the
      dietary level increased. In pigs fed on the 25 g L-arabinose/kg diet, 10.9% of
      the L-arabinose consumed appeared in the urine. This level was increased to 14.7%
      when pigs were fed on a diet containing 100 g L-arabinose/kg diet. Faecal
      digestibility and retention of nitrogen decreased significantly in pigs fed on
      the L-arabinose diets.

PMID- 1390605
TI  - Chromium supplementation in impaired glucose tolerance of elderly: effects on
      blood glucose, plasma insulin, C-peptide and lipid levels.
AB  - Altogether twenty-six elderly subjects (aged 65-74 years) with persistent
      impaired glucose tolerance (World Health Organization (1985) criteria) identified
      in a population-based study, were randomly treated either with chromium-rich
      yeast (160 micrograms Cr/d) or with placebo for 6 months. The 24 h urinary Cr
      increased from 0.13 (SE 0.03) to 0.40 (SE 0.06) micrograms/d in the Cr group (n
      13) but no change was found in the placebo group (n 11) (0.13 (SE 0.02) v. 0.11
      (SE 0.02) micrograms/d). No significant change was observed in the oral glucose
      tolerance test (glucose dose 75 g; 0, 1 and 2 h blood glucose respectively): 5.3
      (SE 0.1), 9.3 (SE 0.3), 8.2 (SE 0.3) mmol/l v. 5.0 (SE 0.1), 8.5 (SE 0.4), 7.3(SE
      0.5) mmol/l in the Cr group; 4.9 (SE 0.2), 9.2 (SE 0.6), 8.1 (SE 0.3) mmol/l v.
      4.8 (SE 0.2), 8.5 (SE 0.5), 7.0 (SE 0.6) mmol/l in the placebo group (baseline v.
      6 months). Glycosylated haemoglobin, plasma insulin, C-peptide and apolipoprotein
      A1 and B levels remained unchanged, and no improvement was seen in serum total
      cholesterol (6.2 (SE 0.3) v. 6.4 (SE 0.3) mmol/l for the Cr group, 6.2 (SE 0.4)
      v. 6.5 (SE 0.3) mmol/l for the placebo group), high-density-lipoprotein
      cholesterol (1.1 (SE 0.1) v. 1.2 (SE 0.1) mmol/l for the Cr group, 1.0 (SE 0.1)
      v. 1.1 (SE 0.1) mmol/l for the placebo group) or triacylglycerols (2.5 (SE 0.4)
      v. 2.0 (SE 0.4) mmol/l for the Cr group, 2.4 (SE 0.2) v. 2.5 (SE 0.2) mmol/l for
      the placebo group). The present results indicate that Cr supplementation does not
      improve glucose tolerance or serum lipid levels in elderly subjects with stable
      impaired glucose tolerance.

PMID- 1390606
TI  - Long-term effect of physical activity on energy balance and body composition.
AB  - We studied the effect of an increase in physical activity on energy balance and
      body composition without interfering with energy intake (EI). Sixteen women and
      sixteen men, aged 28-41 years, body mass index 19.4-26.4 kg/m2, not participating
      in any sport before the start of the experiment, prepared to run a half-marathon
      competition after 44 weeks. Measurements of body composition, EI and energy
      expenditure (EE) were performed before (0 weeks), and 8, 20, and 40 weeks after
      the start of training. Body composition was measured with hydrodensitometry and
      isotope dilution, and EI with a 7 d dietary record. EE was measured overnight in
      a respiration chamber (sleeping metabolic rate (SMR)) and in a number of subjects
      over 2-week intervals with doubly-labelled water (average daily metabolic rate
      (ADMR)). ADMR showed an average increase of 30% in both sexes from the start of
      training onwards while SMR tended to decrease. EI showed a tendency to drop from
      week 20 to week 40 in the men and a tendency to increase from week 20 to week 40
      in the women. Body mass (BM) did not change in both sexes until the observation
      at 40 weeks when the median value of the change in men was -1.0 kg (P < 0.01;
      Wilcoxon signed-rank) while the corresponding change of -0.9 kg in the women was
      not statistically significant. Body composition changes were most pronounced in
      men as well. Based on changes in BM, body volume and total body water, men lost
      3.8 kg fat mass (FM) (P < 0.001; Wilcoxon signed-rank) and gained 1.6 kg protein
      mass (P < 0.01; Wilcoxon signed-rank) while the corresponding changes in women
      were 2.0 kg (P < 0.05; Wilcoxon signed-rank) and 1.2 kg (P < 0.05; Wilcoxon
      signed-rank). In men the loss of FM was positively correlated with the initial
      percentage body fat (Pearson r 0.92, P < 0.001). In conclusion, body fat can be
      reduced by physical activity although women tend to compensate for the increased
      EE with an increased EI, resulting in a smaller effect on BM and FM compared with
      men.

PMID- 1390607
TI  - Effects of an iron supplementation trial on the Fe status of Thai schoolchildren.
AB  - A double-blind clinical trial was conducted among 9- to 11-year-old children in
      sixteen schools in the Chon Buri province of Thailand to assess the effects of an
      iron supplement combined with an anthelminthic agent (i.e. albendazole). In
      addition to the albendazole, Fe or placebo tablets were distributed to 2268
      children enrolled in grades three to five without knowledge of the Fe status of
      the children. Criteria for case inclusion were: (a) absence of A E Bart's or
      haemoglobin (Hb) H disease, (b) absence of abnormal Hb EE, and (c) age, 108-144
      months. The results showed a significant improvement in the Fe status of the
      children after 16 weeks of treatment. The increments were: Hb from 124 to 128
      g/l, serum ferritin from 34.54 to 104.72 micrograms/l, transferrin saturation
      from 24.09 to 35.05%; free erythrocyte protoporphyrin decreased from 444.7 to
      281.4 micrograms/l erythrocytes. These changes were significantly greater than in
      the control group that received only the anthelminthic agent. However, the
      administration of albendazole only also resulted in significant changes in the
      same Fe indicators.

PMID- 1390608
TI  - Dietary iron deficiency and sports anaemia.
AB  - In order to determine whether dietary inadequacies can explain the sub-optimal
      iron status widely documented in endurance-trained athletes, the food intake
      records of Fe-deficient and Fe-replete distance runners and non-exercising
      controls of both sexes were analysed. In all the male study groups the mean
      dietary Fe intake met the recommended dietary allowances (RDA; > 10 mg/d (US)
      Food and Nutrition Board, 1989). However, both female athletes and controls
      failed to meet the RDA with regard to Fe (< 15 mg/d) and folate (< 200
      micrograms/d). There was no difference in the total Fe intakes of Fe-deficient
      and Fe-replete athletes and the controls of each sex. However, Fe-deficient male
      runners, but not female runners, consumed significantly less haem-Fe (P = 0.048)
      than their comparative groups. This suggests that the habitual consumption of Fe
      poor diets is a factor in the aetiology of athletes' Fe deficiency.

PMID- 1390609
TI  - Selenium content of wheat for bread making in Scotland and the relationship
      between glutathione peroxidase (EC 1.11.1.9) levels in whole blood and bread
      consumption.
AB  - The selenium content of the 1989 harvest of wheat used for bread making in
      Scotland ranged from 0.028 microgram/g dry weight for home-grown wheat to 0.518
      microgram/g for Canadian wheat. The tonnage values indicate that 13.8% of the
      wheat used in bread making came from Canada. This reflects in a calculated
      dietary intake of 31 micrograms/d which is well below the recommended levels of
      70 and 55 micrograms for adult males and females respectively (National Research
      Council, 1989). The average glutathione peroxidase (EC 1.11.1.9) level in 478
      samples of human whole blood was 6.08 (SE 0.065) units/ml. This increased to 6.65
      (SE 0.321) in sixty-two subjects consuming brown or wholemeal bread but was
      unaffected by oily fish consumption. Analysis of a small number of samples of
      whole milk, eggs and meat indicated slightly higher concentrations than
      previously published values but this trend was insufficient to compensate for the
      lower cereal provision of Se.

PMID- 1390610
TI  - Bioavailability of magnesium and calcium from cow's milk and soya-bean beverage
      in rats.
AB  - The milk components lactose and casein enhance the apparent absorption of
      magnesium and possibly also of calcium, whereas phytate, which occurs in soya
      bean products, has an inhibitory effect. This implies that soya-bean beverage v.
      cow's milk could lower bioavailability of Mg and Ca. This hypothesis was tested
      in two experiments with growing rats. Feeding soya-bean beverage v. cow's milk
      consistently lowered body-weight gain, enhanced bone turnover, as measured by
      increased plasma alkaline phosphatase (EC 3.1.3.1) activity and increased urinary
      hydroxyproline excretion, and decreased Mg and Ca concentrations in the femur.
      Because the mineral compositions of the soya-bean beverage and the cow's milk
      were different, the intake of Mg was higher in rats fed on soya-bean beverage,
      whereas that of Ca was higher in rats fed on cow's milk. Supplementation of the
      soya-bean beverage either with phosphorus and Ca or with P, Ca and methionine, to
      concentrations identical to those in milk, restored growth and bone
      mineralization. When using diets carefully balanced for Mg, Ca, P, sodium,
      potassium and methionine, soya-bean beverage v. cow's milk in the diets decreased
      apparent absorption and urinary excretion of Mg and Ca. Hydrolysis of lactose in
      milk decreased absorption and urinary excretion of Mg; it did not significantly
      affect Ca absorption but lowered urinary Ca excretion. The present study shows
      that soya-bean beverage v. milk depresses Mg and Ca bioavailability, as would be
      predicted on the basis of reported effects of their purified components.

PMID- 1390611
TI  - Production of chickens with marginal vitamin A deficiency.
AB  - Marginally vitamin A-deficient 1-d-old chickens capable of remaining healthy for
      at least 6 weeks were produced using a two-generation model. In this model, hens
      fed on diets with a limited vitamin A content were used to obtain 1-d-old
      chickens which were marginally deficient in vitamin A. Only hens with a narrow
      range of plasma retinol values (0.60-0.85 mumol/l) were satisfactory for this
      purpose. Above this range the 1-d-old chickens were not marginally vitamin A
      deficient. Below this range egg production and hatchability were affected to some
      extent depending on the degree of vitamin A deficiency. Even when egg production
      and hatchability remained at a high level in such birds, the 1-d-old chickens
      produced were not sufficiently strong to survive the first weeks of life. The
      advantages of the two-generation model for producing marginally vitamin A
      deficient chickens are the increased uniformity and predictability of the
      chickens with respect to body-weight, general health and vitamin A status.
      However, it does take about 3 months to produce such chickens.

PMID- 1390612
TI  - Effect of ileo-rectal anastomosis and post-valve T-caecum cannulation on growing
      pigs. 1. Growth performance, N-balance and intestinal adaptation.
AB  - The effects of post-valve T-caecum (PVTC) cannulation and end-to-side ileo-rectal
      anastomosis (IRA) on growth performance, nitrogen retention and intestinal
      fermentation were measured in growing pigs by comparison with a control group of
      intact animals. There were no differences between PVTC-pigs and intact pigs in
      growth performance and N balance. In IRA-animals reduced growth (P < 0.01), less
      efficient feed conversion (P < 0.01) and decreased N retention (P < 0.001) were
      found. Indices of fermentation measured in ileal digesta of PVTC- and IRA-pigs
      were considerably different. In IRA-animals the concentration of volatile fatty
      acids (VFA) was about 112-162 mmol/l, higher (P < 0.001) than in digesta of PVTC
      pigs (20-31 mmol/l). The molar proportions of acetate and propionate depended (P
      < 0.01 and P < 0.001 respectively) on the digesta-collection technique.
      Concentrations and ratios of VFA measured in PVTC-pigs were similar to reported
      values. Diaminopimelic acid (DAPA) concentration and N:DAPA ratios measured in
      digesta were significantly (P < 0.05 and P < 0.001 respectively) different
      between treatments. All digesta variables measured showed increased microbial
      activity in digesta of IRA-pigs; thus, an influence on digestibility measurement
      can be assumed.

PMID- 1390613
TI  - Inter- and intra-individual variability in food intake of elderly people in
      Perugia (Italy).
AB  - It has been shown that each individual has a considerable day-to-day variation
      (intra-individual variation) in his or her level of food consumption. A large
      intra-individual variation has adverse effects on the reliability of research
      studies. The effect of the intra-individual variation can be minimized by taking
      food intake records over several days. An increase in the number of days entails
      higher costs, and this could limit the practicability of the study. In the recent
      literature on the methodology of dietary surveys, there is a growing interest in
      the estimation of the number of days required to conduct a reliable dietary
      survey. Recent developments in statistical theory allow the problem of large
      intra-individual variability to be overcome. These new statistical techniques
      require knowledge of the intra- and inter-individual variability and the
      appropriate adjustment of the statistical results. The aim of the present study
      was to evaluate the number of days of recorded intake required to obtain an
      estimate of the components of variance (the inter-individual and the intra
      individual variability) focusing on foods rather than nutrients.

PMID- 1390614
TI  - Effect of ileo-rectal anastomosis and post-valve T-caecum cannulation on growing
      pigs. 2. Blood variables and mineral balances.
AB  - In a long-term study nine ileo-rectally anastomosed (IRA) and seven post-valve T
      caecum (PVTC)-cannulated pigs were compared with six intact pigs with regard to
      different blood variables, sodium and potassium retention and weights of selected
      organs. After surgery, apart from urea and K measured 13 weeks post-surgery,
      there were no differences in the blood variables between the PVTC-pigs and intact
      pigs. In IRA-pigs concentrations of creatinine (P < 0.01), Na (P < 0.001), base
      excess (P < 0.001), pH (P < 0.01) and bicarbonate (P < 0.001) in blood were lower
      than those in intact pigs. At 13 weeks after surgery the blood K concentration in
      IRA-pigs was higher (P < 0.001) than that in PVTC-pigs or intact pigs. At 6 weeks
      after surgery the blood urea concentration in IRA-pigs was higher (P < 0.001)
      than that in intact and PVTC-pigs. At 13 weeks after surgery the urea
      concentration in PVTC-pigs was higher (P < 0.001) than those in IRA-pigs or
      intact pigs. The Na (P < 0.01 11 weeks after surgery) and (P < 0.05 and P < 0.01
      5 and 11 weeks after surgery respectively) balances in IRA-pigs were lower than
      those in intact animals. Na retention was negative for IRA-animals 11 weeks after
      surgery. Na and K retentions were similar in PVTC-pigs and in intact pigs. The
      urinary: faecal excretion of Na differed slightly between PVTC-animals and intact
      animals. At 13 weeks after surgery there were no differences in organ weights
      between the PVTC-pigs and intact animals. In the IRA-pigs the weights of the
      liver (P > 0.05), the kidneys (P > 0.05) and the adrenal glands were higher (P <
      0.001) than those in the intact animals.

PMID- 1390615
TI  - Differences in energy metabolism between normal weight 'large-eating' and 'small
      eating' women.
AB  - Nine 'large-eating' (approximately 12 MJ/d) and nine 'small-eating'
      (approximately 5.3 MJ/d) women were selected from the population on the basis of
      diet and activity diaries. At rest and in the post-absorptive state the rate of
      oxygen consumption (VO2)/kg fat-free mass (FFM) and rate of carbon dioxide
      production (VCO2)/kg FFM were 9-17% higher (P < 0.05) in the 'large-eaters' than
      in the 'small-eaters'. As energy expenditure was increased by walking at 2.4, 3.9
      and 5.4 km/h the differences between the two experimental groups for both VO2/kg
      FFM and VCO2/kg FFM were decreased to negligible values, but energy expended on a
      body-weight basis (MJ/kg per min) remained significantly higher (5-10%) in 'large
      eaters'. Oral temperature was also consistently higher (up to 0.5 degrees) in
      this group both at rest and during sitting, standing and walking activities.
      Although the average thermic effect of a standardized liquid meal tended to be
      higher (27%; not significant) in the 'small-eaters', the other results
      demonstrate that the 'large-eating' females had a markedly higher rate of energy
      expenditure at rest and during light physical activities.

PMID- 1390617
TI  - Different effects of casein and soyabean protein on gastric emptying of protein
      and small intestinal transit after spontaneous feeding of diets in rats.
AB  - The effects of dietary casein and soyabean-protein isolate (SPI) on gastric
      emptying and small intestinal transit were observed in rats fed on an 80 g casein
      or 80 g SPI/kg diet. After a 24 h fast, rats were given 2 g of both the test
      diets containing 10 g guanidinated casein/kg diet as a marker protein. The
      amounts of the marker protein remaining in the stomach of the rats fed on the
      casein or SPI diet were similar and decreased to about 50% after 20 min. The
      emptying rate then slowed, especially in the casein group, so that the amount
      leaving the stomach after 1 h in the SPI group was slightly higher (P < 0.05).
      The small intestinal transit of chyme was estimated by a bolus injection of
      colloidal carbon suspension or of colloidal carbon and 3H-labelled polyethylene
      glycol through an implanted duodenal catheter 6 min before death. The average
      value of transit at 12, 20, 40 and 60 min after feeding of SPI diet was about 25%
      faster than that after casein diet. The transit velocity of the SPI group was
      also faster than that of the non-protein group 40 min after feeding. These
      findings reveal that SPI enhances the small intestinal transit of the liquid
      phase of chyme. There was no correlation between the gastric emptying of
      homarginine and small intestinal transit. This result suggest that the small
      intestinal transit of lumen contents is controlled by the dietary protein
      regardless of the gastric emptying of protein.

PMID- 1390616
TI  - Bioavailability of energy, nitrogen, fat, zinc, iron and calcium from rural and
      urban Mexican diets.
AB  - The availabilities of nutrients from a representative rural Mexican diet (RMD)
      and a representative urban Mexican diet (UMD) were evaluated by balance
      experiments in sixteen Mexican women. Compared with UMD, the plant-based RMD led
      to a higher number of defaecations and higher faecal excretion of dry matter,
      fat, nitrogen and energy. Apparent digestibility of N from RMD was only 67%
      compared with 90% from UMD. N balance was 0.4 and 2.6 g/d with RMD and UMD
      respectively (P < 0.001). Apparent digestibility of energy was 89 and 95% from
      RMD and UMD respectively (P < 0.001). Calculation of the metabolizable energy
      (ME) using Atwater's (Atwater & Bryant, 1900) general factors overestimates the
      determined ME in RMD by 8%. The Food and Agriculture Organization/World Health
      Organization/United Nations University (World Health Organization, 1985)
      recommended factors for correction of digestibility of fibre intake overestimate
      energy and protein absorption from RMD. The diets provided similar amounts of
      zinc, and its apparent absorption from RMD was 0.5 mg/d (4.6%) and its balance
      was 0.1 mg/d. This compared with values for UMD of 1.6 mg/d (16%) and 1.2 mg/d
      respectively. Iron intake was higher from RMD (17.4 v. 11.6 mg/d; P < 0.01), but
      apparent absorption was 17 v. 35% and balance was 2.7 and 3.8 mg/d (P < 0.001)
      for RMD and UMD respectively. RMD also contained more calcium (745 v. 410 mg/d)
      but apparent absorption from RMD was negative (-136 v. 15 mg/d) and balance was
      more negative (-197 v. -77 mg/d; P < 0.05). Thus, the content of these minerals
      is not low in the rural diet but their bioavailabilities are poor.

PMID- 1390618
TI  - Effects of subcutaneous melatonin implants during long daylength on voluntary
      feed intake, rumen capacity and heart rate of red deer (Cervus elaphus) fed on a
      forage diet.
AB  - Subcutaneous melatonin implants were administered to castrated hand-reared male
      red deer (Cervus elaphus) during a 63 d period in spring, after which effects on
      voluntary feed intake (VFI), rumen pool size, rumen capacity (i.e. volume) and
      heart rate were measured on four occasions, evenly spread over a 12-month period,
      with the deer individually fed indoors on a diet of lucerne (Medicago sativa)
      chaff. Blood samples for hormone determinations were taken at intervals
      throughout the study. Day-time plasma melatonin concentration was approximately 5
      pg/ml in control animals, whereas during melatonin administration it increased to
      60-150 pg/ml and declined to 30 pg/ml by 142 d after the last implantation.
      Melatonin administration markedly depressed plasma prolactin concentration during
      the period of implantation, but thereafter plasma prolactin concentration rose in
      the treated animals during autumn and winter, whilst it declined in control
      animals over this period. VFI, rumen pool size and heart rate in control animals
      attained highest values in summer and lowest values in winter, showing a
      pronounced seasonal cycle. Melatonin administration depressed all these values in
      late spring and summer and increased all the values in autumn and winter,
      relative to control animals, and appeared to move the cycles by approximately 6
      months. Melatonin-treated animals showed maximum values for all these
      measurements during winter. The castrated male deer showed little seasonal change
      in live weight, which was not affected by melatonin administration. The findings
      support the view that melatonin probably mediates the effect of daylength on
      digestive function in red deer. Rumen capacity remained relatively constant
      throughout the year, but rumen pool size as a proportion of rumen capacity
      increased with increasing VFI.

PMID- 1390619
TI  - Dietary protein level alters oxidative phosphorylation in heart and liver
      mitochondria of chicks.
AB  - To determine the effects of dietary protein level on cardiac and hepatic
      mitochondrial oxidative phosphorylation, chicks were fed on semi-purified diets
      of different protein levels (7, 25, 43 and 61% of metabolizable energy content)
      for 7, 14 and 21 d. All diets were formulated to contain equivalent fat, mineral
      and vitamin contents on a gross energy basis. Cardiac and hepatic mitochondrial
      oxidative phosphorylation rates were assessed polarographically with pyruvate and
      malate as substrates. Cardiac mitochondria isolated from chicks fed on a 43 or
      61% protein-energy diet for 7 d exhibited significantly reduced ADP:oxygen
      (ADP:O) ratios when compared with mitochondria isolated from chicks fed on a
      lower-protein-energy diet. Feeding low- (7%) protein-energy diets for 14 d
      resulted in a relatively increased ADP:O ratio in the heart. Responses of ADP:O
      ratios to protein level in hepatic mitochondria showed more dependency on protein
      level than in heart muscle; at all feeding periods the ADP:O ratio decreased with
      an increase in protein level. As a result, ATP synthesized in the liver,
      expressed as nmol/mg mitochondrial protein per min, significantly decreased with
      increased dietary protein level. A parallel correlation was observed, in chicks
      fed on diets with different levels of protein, between ADP:O ratio for liver
      mitochondria and body fat. These results suggest that the reduction in oxidative
      phosphorylation in the heart and liver of animals fed on a higher protein-energy
      diet may partly contribute to the depression of body fat.

PMID- 1390620
TI  - Drug-induced Creutzfeldt-Jakob like syndrome.
AB  - A patient with progressive neurological deterioration characterized by cognitive
      impairment, myoclonus, Parkinson's syndrome, an abnormal electroencephalogram and
      fasciculations was considered for brain biopsy for suspected Creutzfeldt-Jakob
      disease. Complete clinical recovery followed discontinuation of lithium and
      nortriptyline. Awareness of this unusual drug-induced Creutzfeldt-Jakob like
      syndrome can avoid costly, invasive and unnecessary investigative procedures.

PMID- 1390621
TI  - Case report: acquired antisocial personality disorder associated with unilateral
      left orbital frontal lobe damage.
AB  - We report on our analysis of a patient who developed personality changes which
      strongly resembled an antisocial personality disorder after surgical resection of
      a pituitary tumor. Despite behavioral changes that were obvious to friends,
      family and health care professionals, formal neuropsychological and personality
      testing revealed no specific cognitive deficits or psychopathology. We
      hypothesize that damage to a circumscribed region of the left orbitofrontal
      cortex, illustrated by magnetic resonance imaging, underlies these personality
      alterations. In contrast to previous reports, which ascribe such personality
      changes to bilateral frontal lobe injury, we suggest that unilateral frontal lobe
      damage alone may have resulted in the development of this syndrome.

PMID- 1390622
TI  - Tourette's syndrome and neonatal anoxia: further evidence of an organic etiology.
AB  - Studies of Tourette's syndrome have indicated that the etiology may be either
      primary or secondary. Secondary Tourette's syndrome has been reported in
      association with numerous neurological conditions, but there have been no
      previous reports of Tourette's syndrome and its relationship to neonatal anoxia.
      This report presents the case of a 15-year-old boy with a history of Tourette's
      syndrome and neonatal anoxia and examines whether or not there is a connection
      between the two. To test the hypothesis that this is the first documented case of
      cerebral anoxia at birth followed by Tourette's, a review of the pertinent
      literature on secondary Tourette's syndrome is presented. Evidence of perinatal
      anoxia, subsequent Tourette's syndrome, a negative family history, as well as an
      examination of the statistical chances of anoxia and Tourette's syndrome co
      existing and of all previous reports of acquired Tourette's syndrome tend to
      favor an organic perinatal insult as having caused the later development of
      Tourette's syndrome in the case of this adolescent.

PMID- 1390623
TI  - Analysis of the promoter region of the rat D2 dopamine receptor gene.
AB  - To investigate the regulatory processes involved in the expression of the D2
      dopamine receptor gene, a rat genomic clone was isolated using a 21-mer
      oligonucleotide probe made of exon 1 sequences. A 1.3-kb region including all of
      exon 1, its 5'-flanking region, and part of intron 1 was sequenced. S1 nuclease
      analysis indicated three consecutive nucleotides as the main transcription start
      sites; several weaker sites were also noted between 321 and 363 nucleotides
      upstream from the 3' end of exon 1. The promoter region lacks TATA and CAAT boxes
      and is rich in G+C content with several putative Sp1 binding sites. Transient
      expression assays using chimeric constructs of D2 promoter deletion mutants
      chloramphenicol acetyl-transferase gene in the neuroblastoma cell line NB41A3
      which expresses D2 binding sites indicated strong transcription enhancing
      activity between nucleotides -75 and -30 and silencing activity between
      nucleotides -217 and -76. DNase I footprinting studies using nuclear extract from
      NB41A3 suggested Sp1 binding to its consensus sequence at nucleotide -48 but
      inhibition of Sp1 binding at nucleotide -86 by the extract. The D2 promoter could
      not induce transcription of the heterologous CAT gene in C6 glioma, embryonal NIH
      3T3, or hepatic Hep G2 cells. It is concluded that the rat D2 gene shares with
      the human D1A dopamine receptor gene several features typical of "housekeeping"
      genes but they are both tissue-specific, regulated genes. Unlike the D1A gene,
      however, the D2 gene has a strong preference for transcription initiation to
      three consecutive nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390624
TI  - A small (58-nm) attached sphere perturbs the sieving of 40-80-kilobase DNA in 0.2
      2.5% agarose gels: analysis of bacteriophage T7 capsid-DNA complexes by use of
      pulsed field electrophoresis.
AB  - Although the icosahedral bacteriophage T7 capsid has a diameter (58 nm) that is
      234-fold smaller than the length of the linear, double-stranded T7 DNA, binding
      of a T7 capsid to T7 DNA is found here to have dramatic effects on the migration
      of the DNA during both pulsed field agarose gel electrophoresis (PFGE; the field
      inversion mode is used) and constant field agarose gel electrophoresis (CFGE).
      For these studies, capsid-DNA complexes were obtained by expelling DNA from
      mature bacteriophage T7; this procedure yields DNA with capsids bound at a
      variable position on the DNA. When subjected to CFGE at 2-6 V/cm in 0.20-2.5%
      agarose gels, capsid-DNA complexes arrest at the electrophoretic origin.
      Progressively lowering the electrical potential gradient to 0.5 V/cm results in
      migration; most complexes form a single band. The elevated electrical potential
      gradient (3 V/cm) induced arrest of capsid-DNA complexes is reversed when PFGE is
      used instead of CFGE. For some conditions of PFGE, the mobility of capsid-DNA
      complexes is a function of the position of the capsid on the DNA. During either
      CFGE (0.5 V/cm) or PFGE, capsid-DNA complexes increasingly separate from capsid
      free DNA as the percentage of agarose increases. During these studies, capsid-DNA
      complexes are identified by electron microscopy of enzymatically-digested pieces
      of agarose gel; this is apparently the first successful electron microscopy of
      DNA from an agarose gel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390625
TI  - Conformation of guanine-8-oxoadenine base pairs in the crystal structure of
      d(CGCGAATT(O8A)GCG).
AB  - The structure of the synthetic deoxydodecamer d(CGCGAATT(O8A)GCG)2 (O8A = 8
      oxoadenine) has been determined by single-crystal X-ray diffraction techniques.
      The oligonucleotide crystallizes in the orthorhombic space group P2(1)2(1)2(1)
      with cell dimensions of a = 25.48 A, b = 41.84 A, and c = 64.91 A. The refinement
      has converged with an R-factor of 0.151 for 1119 reflections in the resolution
      range 8.0-2.25 A. Sixty-seven solvent molecules were located during the course of
      the refinement. The B-DNA helix consists of ten Watson-Crick base pairs and two
      guanine-8-oxoadenine (G.O8A) base pairs. In order to achieve hydrogen-bonding
      complementarity between the two bases, an unusual G(anti).O8A-(syn) wobble
      conformation is adopted. It is proposed that the G.O8A mispairs are held together
      by a network of four interbase hydrogen bonds which are the result of the
      formation of two reverse three-center hydrogen-bonding systems. These involve one
      carbonyl oxygen lone pair interacting with two hydrogen atoms. In a departure
      from previous observations of the characteristics of purine-purine anti-syn base
      pairs, lambda 1 and lambda 2, the angles between the glycosidic bonds and the C1'
      C1' vector, are symmetric. A reassessment of the other purine-purine mispairs
      suggests that similar three-center hydrogen bonds may occur and make a
      contribution to stabilizing other base pairings.

PMID- 1390627
TI  - Effect of 5-deazaflavin on energy transduction during catalysis by Escherichia
      coli DNA photolyase.
AB  - DNA photolyase from Escherichia coli contains 1,5-dihydroFAD (FADH2) plus 5,10
      methenyltetrahydropteroylpolyglutamate. The action spectrum observed for
      apoenzyme reconstituted with 5-deazaFADH2 (EdFADH2) matched its absorption
      spectrum after correction for the presence of a small amount of inactive 5
      deazaFADox. The quantum yield for dimer repair with EdFADH2 (phi EdFADH2 = 0.110)
      was 6-fold lower than that observed with apoenzyme reconstituted with FADH2.
      Excited-state redox potential calculations indicate that 5-deazaFADH2 singlet is
      a better one-electron donor (E = -3.5 V) than FADH2 singlet (E = -2.7 V). Other
      studies indicate that the quantum yield for electron transfer from reduced flavin
      singlet to pyrimidine dimer (0.88) is unaffected when FADH2 is replaced by 5
      deazaFADH2. Enhanced back electron transfer from pyrimidine dimer radical to
      flavin radical may account for the decreased quantum yield observed with EdFADH2
      since, in the ground state, 5-deazaFADH. is a better oxidant than FADH.. The
      action spectrum observed for apoenzyme reconstituted with 5-deazaFADH2 plus 5,10
      CH(+)-H4folate (EPtedFADH2) matched the absorption spectrum determined for enzyme
      bound 5-deazaFADH2, indicating that the pterin chromophore was inactive as a
      sensitizer. This differs from results obtained with native enzyme, where pterin
      acts as a sensitizer via efficient singlet-singlet energy transfer to FADH2. The
      quantum yield for dimer repair by 5-deazaFADH2 bound to EPtedFADH2 (phi
      EPtedFADH2 = 0.0318) was 28.9% of that observed for EdFADH2. Spectroscopic
      studies indicate that singlet-singlet energy transfer in EPtedFADH2 is very
      efficient but only occurs in the "wrong" direction, i.e., from excited 5
      deazaFADH2 to pterin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390626
TI  - Differences and similarities in the repair of two benzo[a]pyrene diol epoxide
      isomers induced DNA adducts by uvrA, uvrB, and uvrC gene products.
AB  - We have determined the role of the uvrA, uvrB, and uvrC genes in Escherichia coli
      cells in repairing DNA damage induced by three benzo[a]pyrene diol epoxide
      isomers. Using the phi X174 RF DNA-E. coli transfection system, we have found
      that BPDE-I or BPDE-II modified phi X174 RF DNA has much lower transfectivity in
      uvrA, uvrB, and uvrC mutant cells compared to wild type cells. In contrast, BPDE
      III modification of phi X174 RF DNA causes much less difference in transfectivity
      between wild type and uvr- mutant cells. Moreover, BPDE-I and -II-DNA adducts are
      much more genotoxic than are BPDE-III-DNA adducts. Using purified UVRA, UVRB, and
      UVRC proteins, we have found that these three gene products, working together,
      incise both BPDE-I- and BPDE-III-DNA adducts quantitatively and, more
      importantly, at the same rate. In general, UVRABC nuclease incises on both the 5'
      (six to seven nucleotides) and 3' (four nucleotides) sides of BPDE-DNA adducts
      with similar efficiency with few exceptions. Quantitation of the UVRABC incision
      bands indicates that both of these BPDE isomers have different sequence
      selectivities in DNA binding. These results suggest that although UVR proteins
      can efficiently repair both BPDE-I- and BPDE-III-DNA adducts, in vivo the uvr
      system is the major excision mechanism for repairing BPDE-I-DNA adducts but may
      play a lesser role in repairing BPDE-III-DNA adducts. It is possible the low
      lethality of BPDE-III-DNA adducts is due to less complete blockage of DNA
      replication.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390628
TI  - The C-terminus of the succinate dehydrogenase IP peptide of Saccharomyces
      cerevisiae is significant for assembly of complex II.
AB  - Site-directed mutagenesis was used to introduce mutations into the gene for the
      iron protein (IP) of succinate dehydrogenase (SDH) of Saccharomyces cerevisiae.
      Specifically, three mutations were examined which caused the synthesis of
      truncated IP peptides missing four, seven, or 17 amino acids from the C-terminus,
      respectively. The deletion of seven or more amino acids includes the loss of two
      lysine residues, which appear to have been highly conserved in evolution. While
      the deletion of four amino acids had no effect on the assembly of complex II and
      on its activity, the deletion including the two lysines abolished SDS activity
      completely and led to the failure of the imported IP peptide to be incorporated
      into a stable complex II or SDH complex. Replacement of one of the lysines by
      threonine had no effect, but replacement of both by threonine affected the
      specific activity of complex II but not its assembly and stability.

PMID- 1390629
TI  - Binding of dicyclohexylcarbodiimide to aspartate-155 or glutamate-166 of
      cytochrome b6 in a cytochrome bf complex isolated from spinach thylakoids.
AB  - In a recent study [Wang & Beattie (1991) Arch. Biochem. Biophys. 291, 363-370],
      we reported that dicyclohexylcarbodiimide (DCCD) inhibited proton translocation
      in the cytochrome bf complex reconstituted into proteoliposomes and was bound
      selectively to cytochrome b6. To establish the site of binding of DCCD on
      cytochrome b6, the cytochrome bf complex labeled with [14C]DCCD was selectively
      digested with chymotrypsin and trypsin. A 17-kDa fragment containing radioactive
      DCCD and the heme moiety was obtained after chymotrypsin digestion, while a 12.5
      kDa fragment containing both radioactive DCCD and the heme moiety was obtained
      after trypsin digestion, suggesting that the site of DCCD binding might be on
      aspartate-140, aspartate-155, or glutamate-166. Extensive digestion of cytochrome
      b6 isolated from a [14C]DCCD-labeled cytochrome bf complex with trypsin followed
      by isolation and sequencing of two radioactive peptides obtained revealed that
      DCCD is bound at either residue aspartate-155 or residue glutamate-166 localized
      in amphipathic extramembranous helix IV. In addition, the cytochrome bf complex
      labeled with [14C]DCCD was reconstituted into liposomes and digested with
      trypsin. Three fragments of 9.3, 10.5, and 11.5 kDa were obtained, suggesting
      that the four-helix model for the topography of cytochrome b6 in the membrane is
      correct.

PMID- 1390630
TI  - Chloroplast biogenesis: [4-vinyl] chlorophyllide a reductase is a divinyl
      chlorophyllide a-specific, NADPH-dependent enzyme.
AB  - Some properties of [4-vinyl] chlorophyllide a reductase are described. This
      enzyme converts divinyl chlorophyllide a to monovinyl chlorophyllide a. The
      latter is the immediate precursor of monovinyl chlorophyll a, the main
      chlorophyll in green plants. [4-Vinyl] chlorophyllide a reductase plays an
      important role in daylight during the conversion of divinyl protochlorophyllide a
      to monovinyl chlorophyll a. [4-Vinyl] chlorophyllide a reductase was detected in
      isolated plastid membranes. Its activity is strictly dependent on the
      availability of NADPH. Other reductants such as NADH and GSH were ineffective.
      The enzyme appears to be specific for divinyl chlorophyllide a, and it does not
      reduce divinyl protochlorophyllide a to monovinyl protochlorophyllide a. The
      conversion of divinyl protochlorophyllide a to monovinyl protochlorophyllide a
      has been demonstrated in barley and cucumber etiochloroplasts and appears to be
      catalyzed by a [4-vinyl] protochlorophyllide a reductase [Tripathy, B.C., &
      Rebeiz, C.A. (1988) Plant Physiol. 87, 89-94]. On the basis of reductant
      requirements and substrate specificity, it is possible that two different 4-vinyl
      reductases may be involved in the reduction of divinyl protochlorophyllide a and
      divinyl chlorophyllide a to their respective 4-ethyl analogues.

PMID- 1390631
TI  - Location of functional centers in the microsomal cytochrome P450 system.
AB  - Fluorescence quenching and energy-transfer studies have been carried out to
      determine the position of FAD and FMN groups of NADPH-cytochrome P450 reductase
      and of the heme and substrate groups of cytochrome P450 with respect to the
      lipid/water interphase. Quenching by iodine of the fluorescence of the flavins of
      the reductase shows a biphasic pattern, due to the different accessibility of FAD
      and FMN to the solvent with Stern-Volmer constants of 7.9 x 10(-4) and 2.7 x 10(
      3) mM-1, respectively. Both prosthetic groups appear to be buried within the
      three-dimensional structure of the native reductase, FAD more deeply embedded
      than FMN and with a relative contribution to the total fluorescence of flavins of
      84% (FAD) and 16% (FMN). The lack of significant energy transfer (less than 5%)
      from FAD+FMN to the rhodamine group of the N-labeled phosphatidylethanolamine
      incorporated in membranes reconstituted with NADPH-cytochrome P450 reductase and
      phosphatidylcholine points out that both groups are located at a distance greater
      than 5 nm from the lipid/water interphase. Steady-state fluorescence intensity
      and anisotropy data obtained with native and FMN-depleted NADPH-cytochrome P450
      reductase show that energy transfer between both prosthetic groups occurs in the
      native reductase with an efficiency of ca. 31%, consistent with a separation
      between these groups of 2 nm as suggested earlier by Bastiaens, P. I. H.,
      Bonants, P. J. M., Muller, F., & Visser, A. J. W. G. [(1989) Biochemistry 28,
      8416-8425] from time-resolved fluorescence anisotropy measurements.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390633
TI  - Segmental motion in catalysis: investigation of a hydrogen bond critical for loop
      closure in the reaction of triosephosphate isomerase.
AB  - A residue essential for proper closure of the active-site loop in the reaction
      catalyzed by triosephosphate isomerase is tyrosine-208, the hydroxyl group of
      which forms a hydrogen bond with the amide nitrogen of alanine-176, a component
      of the loop. Both residues are conserved, and mutagenesis of the tyrosine to
      phenylalanine results in a 2000-fold drop in the catalytic activity (kcat/Km) of
      the enzyme compared to the wild-type isomerase. The nature of the closure process
      has been elucidated from both viscosity dependence and primary isotope effects.
      The reaction catalyzed by the mutant enzyme shows a viscosity dependence using
      glycerol as the viscosogen. This dependence can be attributed to the rate
      limiting motion of the active-site loop between the "open" and the "closed"
      conformations. Furthermore, a large primary isotope effect is observed with [1
      2H]dihydroxyacetone phosphate as substrate [(kcat/Km)H/(kcat/Km)D = 6 +/- 1]. The
      range of isotopic experiments that were earlier used to delineate the energetics
      of the wild-type isomerase has provided the free energy profile of the mutant
      enzyme. Comparison of the energetics of the wild-type and mutant enzymes shows
      that only the transition states flanking the enediol intermediate have been
      substantially affected. The results suggest either that loop closure and
      deprotonation are coupled and occur in the same rate-limiting step or that these
      two processes happen sequentially but interdependently. This finding is
      consistent with structural information that indicates that the catalytic base
      glutamate-165 moves 2 A toward the substrate upon loop closure.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390632
TI  - Segmental movement: definition of the structural requirements for loop closure in
      catalysis by triosephosphate isomerase.
AB  - To determine what drives the closure of the active-site loop in the reaction
      catalyzed by triosephosphate isomerase, several residues involved in hydrogen
      bonding between the loop and the bulk of the protein have been altered. It was
      known from earlier work that the loop serves two functions: to stabilize the
      reaction intermediate (and the two transition states that flank it) and to
      prevent the loss of this unstable species into free solution. To discover what
      elements of the protein are necessary for proper closure of the loop, selective
      destabilization of the "open" and the "closed" forms of the enzyme with respect
      to one another has been attempted. The mutant Y164F isomerase has been prepared
      to evaluate the importance of the structure of the "open" form, and the mutant
      E129Q, Y208F, and S211A enzymes have allowed investigation of the "closed" form.
      The integrity of the loop itself has been destabilized by making the T172A
      isomerase. We have found that only those mutations that destabilize the "closed"
      form of the enzyme significantly perturb the catalytic properties of the
      isomerase. The second-order rate constants (kcat/Km) of the S211A and E129Q
      enzymes are reduced 30-fold, and that of the mutant Y208F enzyme is reduced 2000
      fold, from the level of the wild-type enzyme. The dramatic drop in activity of
      the Y208F enzyme is accompanied by a 200-fold increase in the dissociation
      constant of the intermediate analogue phosphoglycolohydroxamate. The most
      important property of the mobile loop of triosephosphate isomerase lies,
      therefore, in the stability of the system when the active site contains ligand
      and the loop is closed.

PMID- 1390634
TI  - Role of Asp-9 and Glu-36 in the active site of the pneumococcal CPL1 lysozyme: an
      evolutionary perspective of lysozyme mechanism.
AB  - The role of carboxylic amino acids Asp-9 and Glu-36 in the activity of CPL1
      lysozyme was investigated by site-directed mutagenesis. The enzymatic activity of
      the single mutants D9E, D9N, D9H, D9K, D9A, E36D, E36Q, E36K, and E36A and of the
      double mutant D9A-E36A was analyzed using a highly sensitive radioactive assay.
      All mutants but D6K showed detectable activities. Interestingly, the mutants E36D
      and E36Q retained 67% and 37% activity, respectively. Amino acid replacements at
      position 9 turned out to be more critical for activity than at position 36. In
      analogy to the mechanism described for hen egg-white lysozyme, where the proton
      donor play a central role, we propose that, in the CPL1 lysozyme, Asp-9 might act
      as the proton donor for activation of the substrate, and Glu-36 could help in the
      stabilization of the intermediate oxocarbocation. The residual activity of
      lysozyme mutants lacking one or two of the acidic amino acids may be explained by
      the participation of a water molecule as proton donor and/or to electrostatic
      contributions in the active center stabilizing the transition state of the
      reaction. Our results are in agreement with the hypothesis that enzymes have been
      optimized during evolution from an ancestral protein able to bind more tightly
      the transition state of the substrate than the substrate itself, by the
      acquisition of amino acids serving a function in catalysis.

PMID- 1390635
TI  - Biochemical characterization of matrilysin. Activation conforms to the stepwise
      mechanisms proposed for other matrix metalloproteinases.
AB  - The latent precursor of matrilysin (EC 3.4.24.23; punctuated metalloproteinase
      (PUMP) was purified from transfected mouse myeloma cell conditioned medium and
      was found to contain one zinc atom per molecule which was essential for catalytic
      activity. Promatrilysin could be activated to the same specific activity by (4
      aminophenyl)mercuric acetate, trypsin, and incubation at elevated temperatures
      (heat activation). Active matrilysin hydrolyzed the fluorescent substrate 2,4
      dinitrophenyl-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH2 at the Gly-Leu bond with a
      maximum value for kcat/Km of 1.3 x 10(4) M-1 s-1 at the pH optimum of 6.5 and pKa
      values of 4.60 and 8.65. Activity is inhibited by the tissue inhibitor of
      metalloproteinases-1 in a 1:1 stoichiometric interaction. Analysis by sodium
      dodecyl sulfate polyacrylamide gel electrophoresis in conjunction with N-terminal
      sequencing revealed that, as with all other matrix metalloproteinases similarly
      studied, promatrilysin activation was accompanied by the stepwise proteolytic
      removal of an M(r) 9000 propeptide from the N-terminus. The intermediates
      generated were dependent on the mode of activation used but, in all cases
      studied, activation terminated with an autocatalytic cleavage at E77-Y78 to yield
      the final M(r) 19,000 active matrilysin. From an analysis of the stability of the
      various intermediates, we propose that the sequence L13-K33 is particularly
      important in protecting the E77-Y78 site from autocatalytic cleavage, thereby
      maintaining the latency of the proenzyme.

PMID- 1390636
TI  - Effects of replacement of active site residue glutamine 231 on activity and
      allosteric properties of aspartate transcarbamoylase.
AB  - Since crystallographic studies on Escherichia coli aspartate transcarbamoylase
      (ATCase) indicate that Gln 231 is in the active site of the enzyme and
      participates in the binding of the substrate, aspartate, it seemed of interest to
      examine mutant enzymes in which Gln 231 was replaced by Asn or Ile. The two
      mutant forms containing amino acid substitutions were characterized by a
      combination of steady-state kinetics, hydrodynamic measurements, and equilibrium
      ligand binding techniques. Both mutant forms exhibited a dramatic reduction in
      the affinity of the protein for substrates and substrate analogues as well as a
      very large decrease in catalytic activity. Moreover, the amino acid substitutions
      introduced within the active site of the enzyme led to unusual allosteric
      properties in the mutant enzymes. Although the bisubstrate analogue N
      (phosphonoacetyl)-L-aspartate promotes the characteristic global conformational
      change in the mutant forms that is observed with the wild-type enzyme, the
      combination of substrate and substrate analogue does not. Cooperativity with
      respect to substrate binding is largely reduced compared to wild-type ATCase.
      Also, the effector molecules ATP and CTP which bind to the regulatory chains have
      dramatic effects on the activity of the mutant enzymes containing replacements
      for Gln 231 in the catalytic chains. In stark contrast to the wild-type enzyme,
      in which effects of nucleotides are manifested primarily by changes in the K0.5
      of the enzyme, ATP and CTP have large effects on the Vmax of the mutant
      enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390637
TI  - Energetic limits of phosphotransfer in the catalytic subunit of cAMP-dependent
      protein kinase as measured by viscosity experiments.
AB  - Viscosogenic agents were used to test the diffusion limits of the reaction
      catalyzed by the catalytic subunit of the cAMP-dependent protein kinase. The
      effects of glycerol and sucrose on the maximum rate (kcat) and the apparent
      second-order rate constants (kcat/Kpeptide) for the phosphorylation of four
      peptidic substrates were measured at their pH optima. The agents were found to
      have moderate to no effect on kcat/Kpeptide for good and poor substrates,
      respectively. Conversely, kcat was highly sensitive to solvent viscosity for
      three of the four peptides at high concentrations of ATP. Taken together, these
      data indicate that enzymatic phosphorylation by the catalytic subunit proceeds
      with rapid or near rapid equilibrium binding of substrates and that all steps
      following the central substrate complex (i.e., chemical and conformational
      events) are fast relative to the rate-determining dissociation of product, ADP,
      when ATP levels are high. Under saturating concentrations of peptide I, LRRASLG,
      an unproductive form of the enzyme is populated. The observed phosphorylation
      rate from this complex is involved in rate limitation owing to a slow step
      separating unproductive and productive enzyme forms. The data are used to
      establish a kinetic mechanism for the catalytic subunit that predicts initial
      reaction velocities under varying concentrations of ATP and substrate.

PMID- 1390638
TI  - Reductive half-reaction in medium-chain acyl-CoA dehydrogenase: modulation of
      internal equilibrium by carboxymethylation of a specific methionine residue.
AB  - Pig kidney medium-chain acyl-CoA dehydrogenase is specifically alkylated at a
      methionine residue by treatment with iodoacetate at pH 6.6. This residue
      corresponds to Met249 in the human medium-chain acyl-CoA dehydrogenase sequence
      [Kelly, D. P., Kim, J. J., Billadello, J. J., Hainline, B. E., Chu, T. W., &
      Strauss, A. W. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 4068-4072]. The S
      carboxymethylated dehydrogenase shows a drastically lowered affinity for octanoyl
      CoA (from submicromolar to 65 microM), but retains about 23% of the maximal
      activity of the native enzyme. In addition, alkylation perturbs the internal
      redox equilibrium: E.FADox.octanoyl-CoA K2 in equilibrium with E.FAD2e.octenoyl
      CoA K2 ranges from about 9 for the native enzyme to about 0.2 for the
      homogeneously modified protein. This effect is not due to a significant change in
      the redox potential of the free enzyme upon alkylation. Rather,
      carboxymethylation weakens the preferential binding of enoyl-CoA product to the
      reduced enzyme (K3) compared to octanoyl-CoA binding to the oxidized
      dehydrogenase (K1) that is required to pull the substrate thermodynamically
      uphill. Thus, the ratio of dissociation constants, K1/K3, decreases from about
      15,000 for the native enzyme to only 330 upon carboxymethylation of Met249.
      Binding studies with a variety of acyl-CoA analogues and manipulation of enzyme
      redox potentials by substitution of the natural prosthetic group by 8-Cl-FAD
      confirm the thermodynamic effects of alkylation.

PMID- 1390639
TI  - A collagen/gelatin-binding decapeptide derived from bovine propolypeptide of von
      Willebrand factor.
AB  - Propolypeptide of von Willebrand factor (pp-vWF) binds to type I collagen, and we
      have reported that a binding domain exists in a 21.5/21-kDa fragment originated
      from the C-terminal portion [Takagi, J., Fujisawa, T., Sekiya, F., & Saito, Y.
      (1991) J. Biol. Chem. 266, 5575-5579]. The collagen-binding property of the
      21.5/21-kDa fragment was compared with that of the intact pp-vWF. Although pp-v
      WF preferentially binds to native type I collagen fibrils, the isolated fragment
      no longer has this specificity and binds well to collagen of other types in the
      native and heat-denatured states. In order to determine the critical site that
      mediates this collagen/gelatin binding, several peptides were synthesized based
      on the primary structure of the 21.5/21-kDa fragment. Among these, a 25-residue
      peptide strongly inhibited the binding of the 125I-labeled 21.5/21-kDa fragment
      to collagen. Using this inhibitory effect as an index, the binding site was
      defined to the sequence as follows: WREPSFCALS. Furthermore, a decapeptide of
      this sequence bound to collagen and gelatin, indicating that this sequence is
      responsible for the binding of the 21.5/21-kDa fragment to collagen/gelatin.

PMID- 1390640
TI  - Triacylglycerol and phospholipid hydrolysis in human plasma lipoproteins: role of
      lipoprotein and hepatic lipase.
AB  - To explore the interactions of triacylglycerol and phospholipid hydrolysis in
      lipoprotein conversions and remodeling, we compared the activities of lipoprotein
      and hepatic lipases on human VLDL, IDL, LDL, and HDL2. Triacylglycerol and
      phospholipid hydrolysis by each enzyme were measured concomitantly in each
      lipoprotein class by measuring hydrolysis of [14C]triolein and
      [3H]dipalmitoylphosphatidylcholine incorporated into each lipoprotein by lipid
      transfer processes. Hepatic lipase was 2-3 times more efficient than lipoprotein
      lipase at hydrolyzing phospholipid both in absolute terms and in relation to
      triacylglycerol hydrolysis in all lipoproteins. The relationship between
      phospholipid hydrolysis and triacylglycerol hydrolysis was generally linear until
      half of particle triacylglycerol was hydrolyzed. For either enzyme acting on a
      single lipoprotein fraction, the degree of phosphohydrolysis closely correlated
      with triacylglycerol hydrolysis and was largely independent of the kinetics of
      hydrolysis, suggesting that triacylglycerol removed from a lipoprotein core is an
      important determinant of phospholipid removal via hydrolysis by the lipase.
      Phospholipid hydrolysis relative to triacylglycerol hydrolysis was most efficient
      in VLDL followed in descending order by IDL, HDL, and LDL. Even with hepatic
      lipase, phospholipid hydrolysis could not deplete VLDL and IDL of sufficient
      phospholipid molecules to account for the loss of surface phospholipid that
      accompanies triacylglycerol hydrolysis and decreasing core volume as LDL is
      formed (or for conversion of HDL2 to HDL3). Thus, shedding of whole phospholipid
      molecules, presumably in liposomal-like particles, must be a major mechanism for
      losing excess surface lipid as large lipoprotein particles are converted to
      smaller particles. Also, this shedding phenomenon, like phospholipid hydrolysis,
      is closely related to the hydrolysis of lipoprotein triacylglycerol.

PMID- 1390641
TI  - Structure and stability of apolipoprotein J-containing high-density lipoproteins.
AB  - Apolipoprotein J (apoJ) defines a heterogeneous subclass of human plasma high
      density lipoproteins (HDL) having a bimodal distribution of molecular mass of 70
      90 kDa (approximately 50%) and 200 kDa or larger (approximately 50%). ApoJ-HDL
      are unstable in stored plasma, and must be evaluated within 24 h. All apoJ-HDL in
      freshly obtained plasma have alpha 2 electrophoretic mobility and are distinct
      from a minor subpopulation of apoAI-HDL which electrophorese in the pre beta
      region. Although apoAI is not associated with the majority of plasma apoJ-HDL, a
      small fraction of these particles also containing apoAI. There is little
      variation in the apoJ/apoAI mole ratio of apoJ-HDL immunoaffinity purified from
      the same individual on different days. In addition, there is a constant ratio
      among individuals, assessed for five volunteers, of 4.9 +/- 0.6. Purified apoJ
      added directly to apoJ-depleted plasma can interact with apoAI or with apoAI
      containing lipoproteins, as evidenced by the association of apoAI with apoJ that
      is reisolated by immunoaffinity chromatography. The amount of apoAI associated
      with apoJ increases linearly with increasing amount of apoJ added, over the range
      of apoJ concentrations tested. No other known apolipoprotein is associated with
      apoJ. By two-dimensional electrophoretic analysis, the lipoproteins containing
      both apoJ and apoAI have approximate molecular masses of 350-400 kDa. Taken
      together, the results suggest that the interaction between apoJ and apoAI is
      physiologically important and that lipoproteins which contain both apoJ and apoAI
      can be produced in the plasma. ApoJ-HDL and apoJ/apoAI-HDL may have different
      functions and metabolic fates or may represent different stages of apoJ
      catabolism.

PMID- 1390642
TI  - Conformation of phosphatidylcholine in neat and cholesterol-containing liquid
      crystalline bilayers. Application of a novel method.
AB  - The conformation of phosphatidylcholine in liquid-crystalline bilayers was
      studied with a novel, high-resolution method employing phosphatidylcholine
      species containing pyrenyl moieties in both acyl chains of variable length.
      Analysis of the intramolecular pyrene-pyrene collision data obtained for 30 such
      species in terms of a simple geometrical model showed that the sn-1 acyl chain
      penetrates, on the average, 0.84 +/- 0.11 methylene units (0.8 A) deeper into the
      bilayer than the sn-2 chain at 22 degrees C. A similar value was obtained at 37
      degrees C. Since the penetration difference of the sn-1 and sn-2 acyl chains is
      inherently coupled to the conformation of the glycerol moiety, these data mean
      that the glycerol moiety of phosphatidylcholine is, on the average, only
      moderately tilted with respect to the bilayer plane in the liquid-crystalline
      state. This contrasts the perpendicular orientation observed previously for
      phosphatidylcholine crystals [Pearson, R. H., & Pascher, I. (1979) Nature 281,
      499-501]. Importantly, addition of 50 mol % cholesterol, which is known to reduce
      dramatically the interactions between phosphatidylcholine molecules in bilayers,
      had only a small effect on the penetration difference of the acyl chains,
      strongly suggesting that the conformation of phosphatidylcholine in the liquid
      crystalline state is determined largely by intramolecular, rather than
      intermolecular, interactions.

PMID- 1390643
TI  - Mapping of the spectral densities of N-H bond motions in eglin c using
      heteronuclear relaxation experiments.
AB  - A new strategy is used for studying the internal motions of proteins based on
      measurements of NMR relaxation parameters. The strategy yields values of the so
      called spectral density functions J(omega) for N-H bond vectors. The spectral
      density functions are related to the distribution of frequencies contained in the
      rotational (overall and internal) motions of these NH bond vectors. No a priori
      model assumptions about the dynamics are required in this approach. The method
      involves measurements of six relaxation parameters consisting of 15N longitudinal
      relaxation rates, transverse relaxation rates of in-phase and antiphase
      coherence, the relaxation rates of heteronuclear 1H-15N two-spin order, the
      heteronuclear 1H-15N nuclear Overhauser effects, and longitudinal relaxation
      rates of the amide protons. The values of the spectral density functions at the
      five frequencies 0, omega N, omega H + omega N, omega H, and omega H - omega N
      are determined from the relaxation parameters using analytical relations derived
      previously [Peng & Wagner (1992) J. Magn. Reson. 98, 308-332]. Here, the method
      is applied to characterize the backbone dynamics of the 15N-enriched proteinase
      inhibitor eglin c, a protein of 70 residues. The values for J(0) and J(omega N =
      50 MHz) vary significantly with the amino acid sequence, whereas the spectral
      densities at higher frequencies, J(450 MHz), J(500 MHz), and J(550 MHz), are
      typically much smaller and show no significant variation with the sequence. The
      collective behavior of the J(omega) values indicate greater internal motion for
      the proteinase binding loop residues and the first eight N-terminal residues. The
      additional internal motion in these regions is in the rate range below 450 MHz.
      The values of J(omega) are also compared with root mean square deviations (rmsds)
      of backbone atoms as obtained in NMR structure determinations. Low values of J(0)
      and J(omega N) are correlated with high rmsds. Spectral densities at higher
      frequencies, J(450 MHz), J(500 MHz), and J(550 MHz), are small and show no
      correlation with rmsds. A comparison with the spectral density functions obtained
      by fitting the experimental data to the functional dependence of the Lipari and
      Szabo formalism [Lipari & Szabo (1982a) J. Am. Chem. Soc. 104, 4546-4559] is
      made.

PMID- 1390644
TI  - Different roles of the two disulfide bonds of the cysteine proteinase inhibitor,
      chicken cystatin, for the conformation of the active protein.
AB  - The Cys-71-Cys-81 disulfide bond of the cysteine proteinase inhibitor, chicken
      cystatin, was specifically reduced by thioredoxin or low concentrations of
      dithiothreitol. This cleavage, followed by S-carbamoylmethylation, induced a
      conformational change of the protein, as evidenced by changes in isoelectric
      point and circular dichroism spectra and by an increased susceptibility to
      digestion by nontarget proteinases. The proteinase binding ability and the
      immunological properties of the inhibitor, however, were not detectably altered,
      indicating that the conformational change was limited to the region around the
      disrupted bond. In contrast, reduction of both disulfide bonds of cystatin by
      higher concentrations of dithiothreitol and subsequent alkylation led to the slow
      conversion of the inhibitor into two forms lacking proteinase binding ability,
      indicative of more extensive conformational changes. Together, these results
      suggest that the less accessible Cys-95-Cys-115 disulfide bond of chicken
      cystatin, but not the more accessible Cys-71-Cys-81 bond, is of importance for
      maintaining the conformation of the inhibitor required for binding of target
      proteinases.

PMID- 1390645
TI  - Modification of the distal histidyl imidazole in myoglobin to N-tetrazole
      substituted imidazole and its effects on the heme environmental structure and
      ligand binding properties.
AB  - The mechanism of N-tetrazole ring formation at the distal histidyl imidazole of
      sperm whale myoglobin (Mb) has been studied by nitrogen-15 (15N) NMR spectroscopy
      by utilizing 15N-labeled cyanogen bromide (BrCN) and azide ion (N3-). The 15N-NMR
      spectrum of BrC15N-modified Mb + N3- afforded two hyperfine-shifted 15N
      resonances, both of which are identical with the resonance positions of two of
      the three 15N resonances for BrCN-modified Mb + 15NN2-. This unusual spectral
      feature is due to the formation of the N-tetrazole ring attached to the distal
      histidyl imidazole and the scrambling of the labeled nitrogen originated from N3-
      or BrCN over the tetrazole ring upon coordination to the ferric heme iron. The
      ferric iron-bound N-tetrazole ring comes off upon reduction to the ferrous state,
      and the stable CO complex of tetrazole-modified Mb (tetrazole-Mb) is formed.
      Electronic absorption and 1H-NMR spectra of deoxy and carbonmonoxy forms of
      tetrazole-Mb are slightly altered from those of native Mb by the modification,
      while the most significant effect is exerted on the C-O stretching frequency of
      iron-bound CO. The C-O stretching band for tetrazole-MbCO is observed at 1966 cm
      1 in contrast to 1945 cm-1 for native MbCO, suggesting that the geometry of iron
      bound CO in tetrazole-Mb is relatively upright which is characteristic of the
      "open" conformer. This result corresponds to the 15-fold increase of the CO
      association rate constant by the N-tetrazole modification of the distal His. The
      oxy form of tetrazole-Mb is readily autoxidized to its ferric state, indicating
      that hydrogen bonding between the distal His and iron-bound oxygen is essential
      for stable O2 binding to the heme iron.

PMID- 1390646
TI  - Human hemoglobin expression in Escherichia coli: importance of optimal codon
      usage.
AB  - The overexpression of a nonfusion product of human beta-globin in Escherichia
      coli from its cDNA sequence has been accomplished for the first time. Expression
      of beta-globin from its native cDNA required the use of the strong bacteriophage
      T7 promoter. In this system, beta-globin accumulated to approximately 10% of
      total E. coli proteins. alpha-Globin was not expressed in the T7 system using the
      native cDNA. For the expression of alpha-globin, synthetic genes containing
      optimal E. coli codons were constructed. Neither synthetic alpha- nor beta-globin
      gene alone was expressed from the lac or tac promoter. Globin expression was
      achieved when the two synthetic alpha- and beta-globin genes were combined as an
      operon downstream of the lac promoter. The two proteins combined intracellularly
      with endogenous heme, which was concomitantly overproduced to yield tetrameric
      hemoglobin as roughly 5-10% of total E. coli protein. Cloning the alpha- and beta
      globin cDNAs in a construct identical with the lac promoter did not yield globin
      production, establishing the requirement for optimal codon usage. The recombinant
      beta-globin from the T7 expression system was purified and reconstituted in vitro
      with heme and native alpha chains. N-terminal analyses showed that the beta
      globin produced in the T7 system and the tetrameric hemoglobin produced from the
      synthetic genes contained an additional beta 1 methionine residue. Two additional
      mutants, beta 1 Val----Met and beta 1 Val----Ala were produced using the T7
      system. Functional and structural properties of the purified hemoglobins will be
      discussed in the following papers.

PMID- 1390648
TI  - High-resolution X-ray study of deoxy recombinant human hemoglobins synthesized
      from beta-globins having mutated amino termini.
AB  - The crystal structures of three mutant hemoglobins reconstituted from recombinant
      beta chains and authentic human alpha chains have been determined in the deoxy
      state at 1.8-A resolution. The primary structures of the mutant hemoglobins
      differ at the beta-chain amino terminus. One mutant, beta Met, is characterized
      by the addition of a methionine at the amino terminus. The other two hemoglobins
      are characterized by substitution of Val 1 beta with either a methionine, beta
      V1M, or an alanine, beta V1A. All the mutation-induced structural perturbations
      are small intrasubunit changes that are localized to the immediate vicinity of
      the beta-chain amino terminus. In the beta Met and beta V1A mutants, the mobility
      of the beta-chain amino terminus increases and the electron density of an
      associated inorganic anion is decreased. In contrast, the beta-chain amino
      terminus of the beta V1M mutant becomes less mobile, and the inorganic anion
      binds with increased affinity. These structural differences can be correlated
      with functional data for the mutant hemoglobins [Doyle, M. L., Lew, G., DeYoung,
      A., Kwiatkowski, L., Noble, R. W., & Ackers, G. K. (1992) Biochemistry preceding
      paper is this issue] as well as with the properties of ruminant hemoglobins and a
      mechanism [Perutz, M., & Imai, K. (1980) J. Mol. Biol. 136, 183-191] that relates
      the intrasubunit interactions of the beta-chain amino terminus to changes in
      oxygen affinity. Since the structures of the mutant deoxyhemoglobins show only
      subtle differences from the structure of deoxyhemoglobin A, it is concluded that
      any of the three hemoglobins could probably function as a surrogate for
      hemoglobin A.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390647
TI  - Functional properties of human hemoglobins synthesized from recombinant mutant
      beta-globins.
AB  - The previous and following articles in this issue describe the recombinant
      synthesis of three mutant beta-globins (beta 1 Val----Ala, beta 1 Val----Met, and
      the addition mutation beta 1 + Met), their assembly with heme and natural alpha
      chains into alpha 2 beta 2 tetramers, and their X-ray crystallographic
      structures. Here we have measured the equilibrium and kinetic allosteric
      properties of these hemoglobins. Our objective has been to evaluate their utility
      as surrogates of normal hemoglobin from which further mutants can be made for
      structure-function studies. The thermodynamic linkages between cooperative
      oxygenation and dimer-tetramer assembly were determined from global regression
      analysis of multiple oxygenation isotherms measured over a range of hemoglobin
      concentration. Oxygen binding to the tetramers was found to be highly cooperative
      (maximum Hill slopes from 3.1 to 3.2), and similar patterns of O2-linked subunit
      assembly free energies indicated a common mode of cooperative switching at the
      alpha 1 beta 2 interface. The dimers were found to exhibit the same
      noncooperative O2 equilibrium binding properties as normal hemoglobin. The most
      obvious difference in oxygen equilibria between the mutant recombinant and normal
      hemoglobins was a slightly lowered O2 affinity. The kinetics of CO binding and O2
      dissociation were measured by stopped-flow and flash photolysis techniques.
      Parallel studies were carried out with the mutant and normal hemoglobins in the
      presence and absence of organic phosphates to assess their allosteric response to
      phosphates. In the absence of organic phosphates, the CO-binding and O2
      dissociation kinetic properties of the mutant dimers and tetramers were found to
      be nearly identical to those of normal hemoglobin. However, the effects of
      organic phosphates on CO-binding kinetic properties of the mutants were not
      uniform: the beta 1 + Met mutant was found to deviate somewhat from normalcy,
      while the beta 1 Val----Met mutant reproduced the native allosteric response.
      Further characterization of the allosteric properties of the beta 1 Val----Met
      mutant was made by measuring the pH dependence of its overall oxygen affinity by
      tonometry. Regulation of oxygen affinity by protons was found to be nearly
      identical to normal hemoglobin from pH 5.8 to 9.3 (0.52 +/- 0.07 protons released
      per oxygen bound at pH 7.4). The present study demonstrates that the equilibrium
      and kinetic functional properties of the recombinant beta 1 Val----Met mutant
      mimic reasonably well those of normal hemoglobin. We conclude that this mutant is
      well-suited to serve as a surrogate system of normal hemoglobin in the production
      of mutants for structure-function studies.

PMID- 1390649
TI  - Purification, crystallization, and preliminary X-ray diffraction analysis of an
      M.HhaI-AdoMet complex.
AB  - The type-II DNA-(cytosine-5)-methyltransferase M.HhaI was overexpressed in
      Escherichia coli and purified to apparent homogeneity. The purification scheme
      exploits a unique high salt back-extraction step to solubilize M.HhaI
      selectively, followed by FPLC chromatography. The yield of purified protein was
      0.75-1.0 mg per gram of bacterial paste. M.HhaI could be isolated in two forms:
      bound with its cofactor S-adenosylmethionine (AdoMet) or devoid of the cofactor.
      The AdoMet-bound form was capable of methylating DNA in vitro in the absence of
      exogenous AdoMet. From kinetic studies of the purified enzyme, values for
      KmAdoMet (60 nM), KiAdoHye (0.4 nM), and Kcat (0.22 s-1) were determined. The
      purified enzyme bound with its cofactor was crystallized by the hanging drop
      vapor diffusion technique. Crystals were of monoclinic space group P2(1) and had
      unit-cell dimensions of a = 55.3 A, b = 72.7 A, c = 91.0 A, and beta = 102.5
      degrees, with two molecules of M.HhaI in each of the two asymmetric units. The
      crystals diffract beyond 2.5 A and are suitable for structure determination.

PMID- 1390651
TI  - Thermodynamics of protein-peptide interactions in the ribonuclease-S system
      studied by molecular dynamics and free energy calculations.
AB  - Hydrophobic interactions between the S-peptide and S-protein in the ribonuclease
      S complex are probed using molecular dynamics simulations and free energy
      calculations. Three successive mutations at the buried position Met13 are
      simulated: Met----Leu, Leu----Ile, and Ile----Val, for which X-ray structures and
      experimental thermodynamic data are available. The calculations give theoretical
      estimates of the changes in binding free energies associated with these
      mutations. The calculated free energy differences are small (0-1.6 kcal/mol), in
      agreement with experiment. However the simulated structures deviate significantly
      from the experimental ones (mean deviation approximately 1.5-2 A), and a large
      uncertainty in the calculated free energies (1-2 kcal/mol) arises from the
      multiple minimum problem. Indeed, multiple conformations are available to the
      side chains around the mutation site, and the sampling of dihedral rotamer
      transitions is limited, despite long simulations. Fluctuations within each local
      minimum give rise to a small statistical error. However the uncertainty due to
      multiple conformations is much greater than the uncertainty due to random
      statistical errors. In our work, an artificial cancellation of errors arose
      because we studied conformations of the RNase complex and of the S-peptide that
      were very similar. In general, the criterion for a precise simulation is not
      merely to reduce the random statistical error, as has been suggested, but rather
      to sample all the important local minima along the mutation pathway, and to
      reduce the statistical error for each one. Our calculations suggest that the
      packing changes associated with the mutations are energetically small and
      localized, and largely cancel when the complex and the S-peptide are compared.
      Solvation of the methionine side chain partial charges in the S-peptide and the
      complex appear to be energetically equivalent, so that removing them (as in Met13
      ---Leu, Ile, Val) does not affect binding. Enthalpy and entropy changes could not
      be estimated reliably.

PMID- 1390650
TI  - Partial denaturation of transthyretin is sufficient for amyloid fibril formation
      in vitro.
AB  - Amyloid diseases are caused by the self-assembly of a given protein into an
      insoluble cross-beta-sheet quaternary structural form which is pathogenic. An
      understanding of the biochemical mechanism of amyloid fibril formation should
      prove useful in understanding amyloid disease. Toward this end, a procedure for
      the conversion of the amyloidogenic protein transthyretin into amyloid fibrils
      under conditions which mimic the acidic environment of a lysosome has been
      developed. Association of a structured transthyretin denaturation intermediate is
      sufficient for amyloid fibril formation in vitro. The rate of fibril formation is
      pH dependent with significant rates being observed at pHs accessible within the
      lysosome (3.6-4.8). Far-UV CD spectroscopic studies suggest that transthyretin
      retains its secondary structural features at pHs where fibrils are formed. Near
      UV CD studies demonstrate that transthyretin has retained the majority of its
      tertiary structure during fibril formation as well. Near-UV CD analysis in
      combination with glutaraldehyde cross-linking studies suggests that a pH-mediated
      tetramer to monomer transition is operative in the pH range where fibril
      formation occurs. The rate of fibril formation decreases markedly at pHs below pH
      3.6, consistent with denaturation to a monomeric TTR intermediate which has lost
      its native tertiary structure and capability to form fibrils. It is difficult to
      specify with certainty which quaternary structural form of transthyretin is the
      amyloidogenic intermediate at this time. These difficulties arise because the
      maximal rate of fibril formation occurs at pH 3.6 where tetramer, traces of
      dimer, and significant amounts of monomer are observed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1390652
TI  - Structure and function of the bacteriophage T4 DNA polymerase holoenzyme.

PMID- 1390653
TI  - On the mechanism of guanosine triphosphate hydrolysis in ras p21 proteins.
AB  - The residue Gln61 is assumed to play a major role in the mechanism of ras p21,
      and mutations of this residue are often found in human tumors. Such mutations
      lead to a major reduction in the rate of GTP hydrolysis by the complex of ras p21
      and the GTPase activating protein (GAP) and lock the protein in a growth
      promoting state. This work examines the role of Gln61 in ras p21 by using
      computer simulation approaches to correlate the structure and energetics of this
      system. Free energy perturbation calculations and simpler electrostatic
      considerations demonstrate that Gln61 is unlikely to serve as the general base in
      the intrinsic GAP-independent reaction of p21. Glutamine is already a very weak
      base in water, and surprisingly the GlnH+ OH-reaction intermediate is even less
      stable in the protein active site than in the corresponding reaction in water.
      The electrostatic field of Glu63, which could in principle stabilize the
      protonated Gln61, is found to be largely shielded by the surrounding solvent.
      However, it is still possible that Gln61 is a general base in the GAP/ras p21
      complex since this system could enhance the electrostatic effect of Glu63. It is
      also possible that the gamma-phosphate acts as general base and that Gln61
      accelerates the reaction by stabilizing the OH- nucleophile. If such a mechanism
      is operative, then GAP may enhance the effect of Gln61 by preorienting its
      hydrogen bonds in the transition-state configuration.

PMID- 1390654
TI  - Proton resonance assignments and three-dimensional solution structure of the
      ragweed allergen Amb a V by nuclear magnetic resonance spectroscopy.
AB  - Essentially complete assignment of the proton resonances in the allergenic
      protein Amb a V has been made by analysis of two-dimensional NMR experiments.
      Conformational constraints were obtained in three forms: interproton distances
      derived from NOE cross-peak intensities of NOESY spectra, torsion angle
      constraints derived from J-coupling constants of COSY and PE-COSY spectra, and
      hydrogen bond constraints derived from hydrogen-exchange experiments.
      Conformations of Amb a V with low constraint violations were generated using
      dynamic simulated annealing in the program XPLOR. The refined structures are
      comprised of a C-terminal alpha-helix, a small segment of antiparallel beta
      sheet, and several loops. A hydrophobic core exists at the interface of the alpha
      helix and beta-sheet. The derived structure accounts for the several anomalous
      proton chemical shifts that are observed. The structure determined here for Amb a
      V is topologically similar to the structure determined previously for the
      homologous allergenic protein Amb t V [Metzler, W. J., Valentine, K., Roebber,
      M., Friedrichs, M. S., Marsh, D., & Mueller, L. (1992) Biochemistry 31, 5117
      5127]; however, significant differences exist in the packing of side chains in
      the hydrophobic core of the molecules. Comparison of the detailed structural
      features of these two proteins will allow us to suggest surface substructures for
      the Amb V allergens that are likely to participate in B cell epitopes.

PMID- 1390655
TI  - 31P-NMR study of the phospholipid moiety of lipophorin subspecies.
AB  - 31P-NMR spectra of four distinct subspecies of Manduca sexta hemolymph lipophorin
      revealed the presence of two resonances separated by 0.6 ppm. Phospholipid
      analysis of the lipoproteins showed that phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE) were present and their mass ratio correlated well
      to the intensity of the two resonances in each of the different subspecies. The
      two resonances persisted in 31P-NMR spectra of organic solvent extracts of
      lipophorin. These results, together with the fact that PE, but not PC, can form
      an intramolecular hydrogen bond between the phosphate oxygen and the amino group
      of ethanolamine, resulting in deshielding of the phosphorus nucleus (and a 0.6
      ppm downfield shift), strongly suggest the resonances observed represent the PC
      and PE components of these lipoproteins. 31P-NMR line-width data obtained as a
      function of temperature and solvent viscosity were used to calculate the chemical
      shift anisotropy (delta sigma), intrinsic viscosity (eta'), and lateral diffusion
      coefficients (DT) of PC and PE in different lipophorin subspecies. eta' and DT
      for PC and PE were similar among high-density lipophorins but differed in low
      density lipophorin (LDLp). These differences may be related to the large increase
      in diacylglycerol content in this particle and/or the association of up to 16
      molecules of apolipophorin III. On the basis of the known lipid compositional
      differences between LDLp and high-density lipophorin subspecies, we propose that
      uptake of large amounts of diacylglycerol during LDLp formation results in
      partitioning of this lipid to the surface monolayer where it intercalates between
      phospholipid molecules. Diacylglycerol intercalation creates gaps between
      phospholipid head groups that expose the hydrophobic surface.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1390657
TI  - Metabolism of [3-13C]pyruvate in TCA cycle mutants of yeast.
AB  - The utilization of pyruvate and acetate by Saccharomyces cerevisiae was examined
      using 13C and 1H NMR methodology in intact wild-type yeast cells and mutant yeast
      cells lacking Krebs tricarboxylic acid (TCA) cycle enzymes. These mutant cells
      lacked either mitochondrial (NAD) isocitrate dehydrogenase (NAD-ICDH1),alpha
      ketoglutarate dehydrogenase complex (alpha KGDC), or mitochondrial malate
      dehydrogenase (MDH1). These mutant strains have the common phenotype of being
      unable to grow on acetate. [3-13C]-Pyruvate was utilized efficiently by wild-type
      yeast with the major intermediates being [13C]glutamate, [13C]acetate, and
      [13C]alanine. Deletion of any one of these Krebs TCA cycle enzymes changed the
      metabolic pattern such that the major synthetic product was [13C]galactose
      instead of [13C]glutamate, with some formation of [13C]acetate and [13C]alanine.
      The fact that glutamate formation did not occur readily in these mutants despite
      the metabolic capacity to synthesize glutamate from pyruvate is difficult to
      explain. We discuss the possibility that these data support the metabolon
      hypothesis of Krebs TCA cycle enzyme organization.

PMID- 1390656
TI  - 13C NMR detection of folate-mediated serine and glycine synthesis in vivo in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae has both cytoplasmic and mitochondrial C1
      tetrahydrofolate (THF) synthases. These trifunctional isozymes are central to
      single-carbon metabolism and are responsible for interconversion of the THF
      derivatives in the respective compartments. In the present work, we have used 13C
      NMR to study folate-mediated single-carbon metabolism in these two compartments,
      using glycine and serine synthesis as metabolic endpoints. The availability of
      yeast strains carrying deletions of cytoplasmic and/or mitochondrial C1-THF
      synthase allows a dissection of the role each compartment plays in this
      metabolism. When yeast are incubated with [13C]formate, 13C NMR spectra establish
      that production of [3-13C]serine is dependent on C1-THF synthase and occurs
      primarily in the cytosol. However, in a strain lacking cytoplasmic C1-THF
      synthase but possessing the mitochondrial isozyme, [13C]formate can be
      metabolized to [2-13C]glycine and [3-13C]serine. This provides in vivo evidence
      for the mitochondrial assimilation of formate, activation and conversion to
      [13C]CH2-THF via mitochondrial C1-THF synthase, and subsequent glycine synthesis
      via reversal of the glycine cleavage system. Additional supporting evidence of
      reversibility of GCV in vivo is the production of [2-13C]glycine and [2,3
      13C]serine in yeast strains grown with [3-13C]serine. This metabolism is
      independent of C1-THF synthase since these products were observed in strains
      lacking both the cytoplasmic and mitochondrial isozymes. These results suggest
      that when formate is the one-carbon donor, assimilation is primarily cytoplasmic,
      whereas when serine serves as one-carbon donor, considerable metabolism occurs
      via mitochondrial pathways.

PMID- 1390658
TI  - Synchrotron radiation solution X-ray scattering study of the pH dependence of the
      quaternary structure of yeast pyruvate decarboxylase.
AB  - The pH dependence of the quaternary structure of pyruvate decarboxylase from
      yeast was studied in the range 6.2 less than pH less than 8.4. There is an
      equilibrium with a midpoint around pH 7.5 between tetramers and dimers, and the
      catalytic activity of the enzyme depends on the volume fraction of tetramer. This
      equilibrium may provide an additional regulating mechanism besides substrate
      activation since accumulation of pyruvate would lead to a reduction in pH and
      hence an increase of the concentration of the catalytically active tetramer.
      Radiation damage during the X-ray scattering experiments results in a shift of
      this equilibrium and in the formation of octamers. These effects could be
      circumvented and analyzed using experimental and data processing methods which
      can be readily applied to other radiation-sensitive systems. The low-resolution
      shapes of the dimers and tetramers were determined from the scattering curves
      using spherical harmonics. The results indicate that a conformational change must
      occur in the dimers upon formation of the tetramers, in agreement with earlier
      circular dichroism measurements.

PMID- 1390659
TI  - High-resolution X-ray structures of pig metmyoglobin and two CD3 mutants:
      Mb(Lys45----Arg) and Mb(Lys45----Ser).
AB  - The structure of pig aquometmyoglobin has been refined to a crystallographic R
      factor of 19.8% against X-ray diffraction data between 10- and 1.75-A spacing.
      The final structural model comprises two molecules of pig myoglobin, 233 water
      molecules, and two sulfate ions. A water molecule is coordinated to each of the
      heme iron atoms with an average Fe-OH2 bond distance of 2.19 A, and the mean Fe-N
      epsilon (proximal histidine-93) distance is 2.20 A. In contrast to the structure
      of sperm whale metmyoglobin, the iron is not significantly displaced from the
      plane of the heme. At the entrance to the heme pocket, the side-chain amino group
      of lysine-45 (CD3) is well-defined in the electron density map and forms salt
      bridging interactions with the heme 6-propionate and with a sulfate ion. Serine
      and arginine replacements have been made previously at position 45 to examine the
      proposal that the CD3 side chain acts as a barrier to ligand entry into the
      protein. Crystal structures of the arginine-45 and serine-45 mutant metmyoglobins
      have been solved to 1.9 and 2.0 A resolution, respectively. In both cases the
      structural changes are confined to the site of mutation. Arginine-45 takes up a
      conformation closely similar to that observed for this residue in wild-type sperm
      whale myoglobin, in which it makes more extensive charge-charge and charge-dipole
      interactions and appears to restrict the movement of the distal histidine away
      from the ligand. The hydroxyl group of serine-45 is disordered, but it is clear
      that the effect of the mutation is to open up the solvent-exposed face of the
      heme pocket.

PMID- 1390660
TI  - Catalytic center of cyclodextrin glycosyltransferase derived from X-ray structure
      analysis combined with site-directed mutagenesis.
AB  - An X-ray structure analysis of a crystal of mutant Asp229----Ala of cyclodextrin
      glycosyltransferase from Bacillus circulans (Ec 2.4.1.19) that had been shortly
      exposed to beta-cyclodextrin showed density corresponding to a maltose bound at
      the catalytic center. The crystal structure was refined to an R-factor of 18.7%
      at 2.5-A resolution. The catalytic center is defined by homology with the
      structurally known alpha-amylases and by the observation that mutants Asp229---
      Ala and Asp328----Ala are almost inactive. By model building, the density-defined
      maltose was extended to a full beta-cyclodextrin, which then indicated the
      general locations of seven subsites for glucosyl units. The catalytically
      competent residues Asp229, Glu257, and Asp328 are at the reducing end of the
      density-defined maltose. In the unligated wild-type structure, Glu257 and Asp328
      form a 2.6-A hydrogen bond between their carboxylates in an arrangement that
      resembles those of the catalytically competent carboxylates in acid proteases.
      Presumably, the first catalytic step is an attack of the proton between Glu257
      and Asp328 on the oxygen of the glycosidic bond.

PMID- 1390661
TI  - Functional signal peptide reduces bilayer thickness of phosphatidylcholine
      liposomes.
AB  - To investigate the interaction between a signal peptide and the lipid bilayer,
      two kinds of peptides, L8-M5 (L8 = MRL8PLAALG, M5 = KVFER) and L14-M5 (L14 =
      MRL14PLAALG), were examined in membranes composed of dioleoylphosphatidylcholine
      (DOPC). Peptides L8 and L14 are artificially designed signal sequences, and M5 is
      the N-terminal five residues of human lysozyme; L8 mediated effective secretion
      of human lysozyme in yeast, while L14 did not [Yamamoto, Y., et al. (1987)
      Biochem. Biophys. Res. Commun. 149, 431-436]. DOPC liposomes incorporating L8-M5
      or L14-M5 were observed by electron cryomicroscopy as pairs of concentric
      circles, and the separation of the bilayer was measured along the membrane.
      Peptide L8-M5 was found to reduce the bilayer thickness, but L14-M5 did not. CD
      measurements revealed that L8-M5 adopted an alpha-helical conformation with
      random coil in the liposome membranes and that L14-M5 adopted a more helical and
      less random conformation than L8-M5. Fluorescence spectroscopy using both aqueous
      and membranous probes revealed that L8-M5 destabilized the lipid bilayer more
      strongly than L14-M5. These results suggest that functional L8-M5 reduces the
      bilayer thickness and destabilizes the lipid bilayer and that these activities
      are important for signal peptide function.

PMID- 1390662
TI  - Changing the inhibitory specificity and function of the proteinase inhibitor
      eglin c by site-directed mutagenesis: functional and structural investigation.
AB  - Amino acids in the serine proteinase inhibitor eglin c important for its
      inhibitory specificity and activity have been investigated by site-directed
      mutagenesis. The specificity of eglin c could be changed from elastase to trypsin
      inhibition by the point mutation Leu45----Arg (L45R) in position P1 [nomenclature
      according to Schechter and Berger (1967) Biochem. Biophys. Res. Commun. 27, 157
      162]. Model building studies based on the crystal structure of mutant L45R [Heinz
      et al. (1991) J. Mol. Biol. 217, 353-371] were used to rationalize this
      specificity change. Surprisingly, the double mutant L45R/D46S was found to be a
      substrate of trypsin and various other serine proteinases. Multidimensional NMR
      studies show that wild-type eglin c and the double mutant have virtually
      identical conformations. In the double mutant L45R/D46S, however, the N-H bond
      vector of the scissile peptide bond shows a much higher mobility, indicating that
      the internal rigidity of the binding loop is significantly weakened due to the
      loss or destabilization of the internal hydrogen bond of the P1' residue. Mutant
      T44P was constructed to examine the role of a proline in position P2, which is
      frequently found in serine proteinase inhibitors [Laskowski and Kato (1980) Annu.
      Rev. Biochem. 49, 593-626]. The mutant remains a potent elastase inhibitor but no
      longer inhibits subtilisin, which could be explained by model building. Both
      Arg51 and Arg53, located in the core of the molecule and participating in the
      hydrogen bonding network with residues in the binding loop to maintain rigidity
      around the scissile bond, were individually replaced with the shorter but equally
      charged amino acid lysine. Both mutants showed a decrease in their inhibitory
      potential. The crystal structure of mutant R53K revealed the loss of two hydrogen
      bonds between the core and the binding loop of the inhibitor, which are partially
      restored by a solvent molecule, leading to a decrease in inhibition of elastase
      by 2 orders of magnitude.

PMID- 1390663
TI  - Primary structure of barwin: a barley seed protein closely related to the C
      terminal domain of proteins encoded by wound-induced plant genes.
AB  - Barwin is a basic protein with pI above 10 and molecular mass 13.7 kDa isolated
      from aqueous extracts of barley seed. The complete amino acid sequence of 125
      residues has been determined by a combination of conventional protein sequencing,
      plasma desorption mass spectrometry, and 1H nuclear magnetic resonance
      spectroscopy. Three disulfide bridges have been localized as Cys31-Cys63, Cys52
      Cys86, and Cys66-Cys123 both by 1H nuclear magnetic resonance spectroscopy and by
      plasma desorption mass spectrometry. The N-terminal residue was identified as
      pyroglutamate. Barwin is closely related to a peptide segment of 122 residues at
      the C-terminal region of the proteins encoded by two wound-induced genes in
      potato plants, win1 and win2, and a protein encoded by the hevein gene of rubber
      tree. In 77 sequence positions of 125 the barwin, win1, win2, and hevein protein
      sequences have amino acid sequence identity, when two gaps--one of two residues
      allowing for the insert of Gly23 and Ala24 and one allowing for the insert of
      Thr97 in the barwin sequence--are introduced in the latter three. The close
      sequence similarity with the proteins encoded by the wound-induced potato and
      rubber tree genes and the ability of the protein to bind saccharides suggest that
      barwin might belong to a group of proteins involved in a common defense mechanism
      in plants.

PMID- 1390664
TI  - Secondary structure in solution of barwin from barley seed using 1H nuclear
      magnetic resonance spectroscopy.
AB  - Barwin, a basic protein from barley seed of 125 amino acid residues, has been
      studied by two-dimensional 1H nuclear magnetic resonance spectroscopy. This
      protein is closely related to the C-terminal domain of proteins whose synthesis
      is induced by wounding, the so-called win proteins. These proteins may,
      therefore, have a role in the defense against fungal attack. Full assignment of
      the 1H nuclear magnetic resonances has been obtained for 104 amino acid residues,
      and 18 amino acid spin systems were partially assigned. Sequence-specific
      assignment using nuclear Overhauser spectroscopy has been achieved for 122 of the
      125 residues. This has revealed that the secondary structure of the protein is
      dominated by a large four-stranded antiparallel beta-sheet consisting of the
      strands Gln2-Thr9, Lys65-Asn71, Gln77-Arg81, and His113-Val121, a small parallel
      beta-sheet of the strands Trp48-Cys52 and Asp84-Ala87, which together account for
      a third of the protein. Sequential effects indicate the presence of three small
      alpha-helices, Tyr30-Lys38, Leu40-Tyr46, and Thr97-Asp103. The secondary
      structure in other regions of the sequence is characterized mainly by loops and
      turns and regions where no regular secondary structure arrangement could be
      identified. A large number of long-range nuclear Overhauser effects has been
      identified, and these have been used, together with sequential and intranuclear
      Overhauser effects, for a calculation of the protein's three-dimensional
      structure.

PMID- 1390665
TI  - Three-dimensional structure in solution of barwin, a protein from barley seed.
AB  - The solution structure of a 125-residue basic protein, barwin, has been
      determined using 1H nuclear magnetic resonance spectroscopy. This protein is
      closely related to domains in proteins encoded by wound-induced genes in plants.
      Analysis of the 1H nuclear Overhauser spectrum revealed the assignment of more
      than 1400 nuclear Overhauser effects. Twenty structures were calculated based on
      676 nontrivial distance restraints, 152 torsion angle restraints (92 phi, 56 chi
      1, and 4 omega for proline), and stereospecific assignments of 38 chiral centers,
      using distance geometry, simulated annealing, and restrained energy minimization.
      None of the distance restraints was violated by more than 0.5 A in any of the 20
      structures, and none of the torsion angle restraints was violated by more than 1
      degree in any of the structures. The RMS difference between the calculated and
      target interproton distance restraints is 0.033 A, and the average atomic RMS
      differences between the 20 structures and their geometric average are 1.23 A for
      backbone atoms and 1.73 A for all heavy atoms. The dominating structural feature
      of the protein is a well-defined four-stranded antiparallel beta-sheet, two
      parallel beta-sheets packed antiparallel to each other and four short alpha
      helices. The binding site of barwin to the tetramer N-acetylglucosamine has been
      qualitatively investigated, and the dissociation constant of the complex has been
      determined using one-dimensional 1H nuclear magnetic resonance spectroscopy.

PMID- 1390666
TI  - Effect of trifluoroethanol on protein secondary structure: an NMR and CD study
      using a synthetic actin peptide.
AB  - The structure of a synthetic peptide comprising the 28 amino-terminal residues of
      actin has been examined by 1H-NMR and CD spectroscopy. The peptide is largely
      unstructured and flexible in solution but becomes increasingly structured at
      higher trifluoroethanol (TFE) concentrations. As judged by CD with the use of two
      additional peptides (actin 1-20 and actin 18-28), TFE induces formation of up to
      48% helical content within residues 1-20, while residues 21-28 exhibit no helical
      propensity. Similar results were obtained by using NMR-derived distance
      information in restrained molecular dynamics calculations. The calculated
      structure of actin 1-28 peptide in 80% TFE is well defined for the first 23
      residues with a backbone root mean square deviation of 0.5 A. Two helices are
      formed from residues 4-13 and 16-20, and a beta-turn is formed from residues 13
      16. The N-terminal residues 1-3 exhibit increased flexibility and a helix-like
      conformation while the C-terminal residues 21-28 show no regular secondary
      structure. These results are compared with the predicted secondary structure and
      the structure of the corresponding sequence in the crystal structure of actin
      [Kabsch et al. (1990) Nature 347, 37-44]. The significance of the TFE-induced
      peptide structure is discussed.

PMID- 1390667
TI  - Total solid-phase synthesis and prolactin-inhibiting activity of the gonadotropin
      releasing hormone precursor protein and the gonadotropin-releasing hormone
      associated peptide.
AB  - The human gonadotropin-releasing hormone precursor protein, pHGnRH (Met-23-Ile69)
      (preproGnRH), and three of its fragment peptides, pHGnRH (Asp14-Ile69)
      (gonadotropin-releasing hormone associated peptide--GAP), pHGnRH (Phe38-Ile69),
      and pHGnRH (Ser47-Ile69), were assembled in a stepwise solid-phase cosynthesis
      employing Boc/Bzl tactics and an optimized acylation schedule which included
      recoupling steps with hexafluoro-2-propanol to help overcome the aggregation of
      the pendant peptide chains of the peptidoresin during difficult couplings.
      Reversed-phase high-performance liquid chromatography (HPLC) purification yielded
      products which were characterized by analytical reversed-phase HPLC, ion-exchange
      chromatography, capillary zone electrophoresis, SDS-polyacrylamide gel
      electrophoresis, and ion-spray mass spectrometry to reveal a high degree of
      homogeneity. Biological characterization demonstrated that only GAP stimulated
      luteinizing hormone and follicle-stimulating hormone release from primary
      cultures of rat anterior pituitary cells, while GAP, pHGnRH (Phe38-Ile69), and
      preproGnRH all inhibited prolactin release, with the latter being the most potent
      at concentrations comparable to bromocryptine. However, only GAP and pHGnRH
      (Phe38-Ile69) were able to displace a labeled gonadotropin-releasing hormone
      agonist from binding to rat pituitary membrane preparations. This first
      demonstration of significant biological activity with a precursor protein also
      suggests that the gonadotropin-releasing and prolactin release-inhibiting
      functions of GAP are not mediated through the same pituitary receptors.

PMID- 1390668
TI  - Calorimetric study of the heat and cold denaturation of beta-lactoglobulin.
AB  - Temperature-induced changes of the states of beta-lactoglobulin have been studied
      calorimetrically. In the presence of a high concentration of urea this protein
      shows not only heat but also cold denaturation. Its heat denaturation is
      approximated very closely by a two-state transition, while the cold denaturation
      deviates considerably from the two-state transition and this deviation increases
      as the temperature decreases. The heat effect of cold denaturation is opposite in
      sign to that of heat denaturation and is noticeably larger in magnitude. This
      difference in magnitude is caused by the temperature-dependent negative heat
      effect of additional binding of urea to the polypeptide chain of the protein upon
      its unfolding, which decreases the positive enthalpy of heat denaturation and
      increases the negative enthalpy of cold denaturation. The binding of urea
      considerably increases the partial heat capacity of the protein, especially in
      the denatured state. However, when corrected for the heat capacity effect of urea
      binding, the partial heat capacity of the denatured protein is close in magnitude
      to that expected for the unfolded polypeptide chain in aqueous solution without
      urea but only for temperatures below 10 degrees C. At higher temperatures, the
      heat capacity of the denatured protein is lower than that expected for the
      unfolded polypeptide chain. It appears that at temperatures above 10 degrees C
      not all the surface of the beta-lactoglobulin polypeptide chain is exposed to the
      solvent, even in the presence of 6 M urea; i.e., the denatured protein is not
      completely unfolded and unfolds only at temperatures lower than 10 degrees
      C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390669
TI  - Stabilization of a protein by removal of unfavorable abnormal pKa: substitution
      of undissociable residue for glutamic acid-35 in chicken lysozyme.
AB  - Glu35 in chicken lysozyme has an abnormally high pKa (6.1) partly due to the
      hydrophobic environment provided by Trp108. The relationship between protein
      stability and abnormal pKa was investigated in detail by using mutant lysozymes
      in which Glu35 was replaced by undissociable residues and an oppositely ionizable
      residue. It was found that lysozyme was stabilized at alkaline pH range by the
      replacement of Glu35 with an undissociable residue, Gln (E35Q lysozyme) or Al
      (E35A lysozyme). On the other hand, when Glu35 was replaced by His (E35H
      lysozyme), which could have an opposite charge to Glu by ionization, the
      introduced His35 was found to have an abnormally low pKa (3.6), leading to the
      destabilization of lysozyme at acidic pH. These observations are completely
      consistent with the situation that the environment around Glu35 is highly
      hydrophobic and therefore the placement of either a positive or negative charge
      in such an environment leads to destabilization of lysozyme. These observations
      also indicate that the replacement of an acidic residue having abnormally high
      pKa or a basic residue having abnormally low pKa by an undissociable residue is a
      very efficient and general method for stabilization of a protein.

PMID- 1390670
TI  - Thermodynamic measurements of the contributions of helix-connecting loops and of
      retinal to the stability of bacteriorhodopsin.
AB  - Thermodynamic studies of bacteriorhodopsin (BR) have been undertaken in order to
      investigate the factors that stabilize the structure of a membrane protein. The
      stability of the native, intact protein was compared to that of protein with
      retinal removed, and/or cleaved in one or two of the loops connecting the
      transmembrane helices. The stability was assessed using differential scanning
      calorimetry and thermal denaturation curves obtained from ultraviolet circular
      dichroism and absorption spectroscopy. Retinal binding and the loop connections
      were each found to make a small contribution to stability, and even a sample that
      was cleaved twice as well as bleached to remove retinal denatured well above room
      temperature. Removal of retinal destabilized the protein more than cleaving once,
      and about as much as cleaving twice. Retinal binding and the connections in the
      loops were found to stabilize BR in independent ways. Cleavage of the molecule
      into fragments did not reduce the intermolecular cooperativity of the
      denaturation. Dilution of the protein by addition of excess lipid in order to
      eliminate the purple membrane crystal lattice also did not alter the
      cooperativity. These results are used to compare the relative importance of
      various contributors to the stability of BR.

PMID- 1390672
TI  - Rate of release of Ca2+ following laser photolysis of the DM-nitrophen-Ca2+
      complex.
AB  - The determination of the rate of release of Ca2+ by pulsed photolysis of the
      photolabile chelator DM-nitrophen is important for its use in time-resolved
      physiological studies: the rate of substrate or effector release should be faster
      than the processes they initiate. Flash photolysis of DM-nitrophen using a 50-ns
      pulse from a frequency-doubled ruby laser (with emission at 347 nm having energy
      of ca. 10-20 mJ) yields short-lived photochromic or aci-nitro intermediates. At
      pH 6.9, double-exponential decay of a photochromic intermediate was observed for
      DM-nitrophen itself and its Ca2+ complex (tau 1/2 values of 24 and 570
      microseconds, and 32 and 220 microseconds respectively), while only
      monoexponential decay of the DM-nitrophen-Mg2+ complex was detected (tau 1/2 = 31
      microseconds). Only the photochemistry of DM-nitrophen-Ca2+ was found to be pH
      sensitive (monoexponential decay, tau 1/2 approximately 115 microseconds at pH
      7.9 and 8.9). Use of the Ca(2+)-sensitive metallochromic dye antipyrylazo III in
      conjunction with pulsed photolysis of DM-nitrophen-Ca2+ enabled an upper limit of
      the half-time of release of Ca2+ to be established of ca. 180 microseconds (the
      rate of association of Ca2+ with the dye was probably rate determining). The rate
      of Ca2+ photorelease may, however, be faster than this. Thus, the DM-nitrophen
      Ca2+ complex releases Ca2+ on photolysis sufficiently rapidly for the study of
      many Ca(2+)-dependent physiological processes with improved kinetic resolution
      over conventional mixing methods.

PMID- 1390671
TI  - Molecular dynamics simulation of bovine prothrombin fragment 1 in the presence of
      calcium ions.
AB  - Early solvation-induced structural reorganization of calcium prothrombin fragment
      1 is simulated with molecular dynamics. Initial coordinates are those of the 2.2
      A resolution crystal structure [Soriano-Garcia, M., Padmanabhan, K., de Vos, A.
      M., & Tulinsky, A. (1992) Biochemistry 31, 2554-2556]. The molecular dynamics
      code AMBER, appropriately modified to include long-range (less than or equal to
      22.0 A) ionic forces, was employed. The solution structure appears to equilibrate
      within 100 ps. Although minor changes are seen in various structural domains, the
      early solution structure basically maintains an intricate network of nine gamma
      carboxyglutamic acid (Gla) residues encapsulating seven calcium ions. However,
      the Gla domain moves with respect to the kringle domain. This motion is mainly
      due to the movement of Ser34-Leu35 that appears to be a flexible hinge between
      the domains. The N-terminus of Ala 1 is in a tightly bound complex with three Gla
      residues that remains stable in the solution structure when the long-range
      electrostatic cutoff is employed and the near planar alignment of the seven
      calcium ions is only slightly distorted. The simulation structure is discussed in
      terms of experiments that studied calcium ion-induced quenching of the intrinsic
      fluorescence, protection of the N-terminal amino group from acetylation by
      calcium ions, chemical modification of the N-terminus to a trinitrophenyl
      derivative, and the possibility of a calcium-binding site(s) in the kringle
      domain.

PMID- 1390673
TI  - Cytochrome P450-benzphetamine interactions in the endoplasmic reticulum: studies
      using a monoclonal antibody to P450b.
AB  - A monoclonal antibody (MAb) to phenobarbital-induced rat cytochrome P450b was
      used to study the interaction of the substrate benzphetamine (Bz) with
      cytochromes P450 in liver microsomes. Binding of Bz to liver microsomes from
      phenobarbital-treated rats was monitored by the substrate-induced type I spectral
      change. The MAb maximally inhibited this spectral change by 49%, providing a
      probe to distinguish MAb-specific P450b from other Bz-binding P450s.
      Thermodynamic parameters of the interaction were determined in the absence and
      presence of MAb. The MAb did not influence the spin-state equilibrium of
      substrate-free P450b, but it increased the low spin content of substrate-bound
      P450b. The MAb also decreased the affinity of both high and low spin P450b for
      Bz. The temperature dependence of the Bz-binding interactions revealed a
      transition near 20 degrees C. Fluorescence polarization measurements of the
      membrane probe 1,6-diphenyl-1,3,5-hexatriene also revealed a transition at this
      temperature. The MAb comparably inhibited Bz binding to high spin P450b in the
      low and high temperature regions, whereas MAb inhibition of Bz binding to low
      spin P450b was greater in the low temperature region than in the high temperature
      region. These results indicate temperature-dependent changes in membrane
      structure that modulate both Bz binding to P450b and MAb-P450b-Bz interactions.
      These results also demonstrate the utility of MAbs for evaluating P450-substrate
      binding microequilibria of MAb-specific P450s in the presence of other P450s
      while in the natural membrane environment of the endoplasmic reticulum.

PMID- 1390674
TI  - Kinetics of basic fibroblast growth factor binding to its receptor and heparan
      sulfate proteoglycan: a mechanism for cooperactivity.
AB  - Basic fibroblast growth factor (bFGF) binds to cell surface receptor (CSR)
      proteins and to heparan sulfate proteoglycans (HSPG). On the basis of equilibrium
      dissociation constants (Kd), the CSR has been considered a "high-affinity"
      binding site and HSPG a "low-affinity" site. We measured the apparent individual
      on and off rate constants (kon and koff) for bFGF binding to these two sites on
      intact cells and to each class of binding site in the absence of the other. While
      the kon's for CSR and HSPG on intact cells were not statistically different (konC
      = 2.27 x 10(8) M-1 min-1; konH = 0.90 x 10(8) M-1 min-1), the koff for the HSPG
      was 22.7-fold greater than that for the CSR (koffC = 0.003 min-1; koffH = 0.68
      min-1). Thus, the difference in Kd's appears to result from the faster rate at
      which bFGF is released from the HSPG sites compared to the CSR. The kon's for
      isolated CSR and HSPG, and the koff for isolated HSPG, did not differ
      significantly from those for intact cells konC = 2.50 x 10(8) M-1 min-1; konH =
      0.92 x 10(8) M-1 min-1; koffH = 0.095 min-1). However, the off rate for isolated
      CSR (koffC = 0.048 min-1) was statistically indistinguishable from the off rate
      for HSPG and 16-fold greater than the off rate for CSR on intact cells. The "high
      affinity" binding of bFGF to intact cells probably refers only to a complex of
      bFGF with both CSR and HSPG, and not to the CSR alone.

PMID- 1390675
TI  - High-affinity calmodulin binding is required for the rapid entry of Bordetella
      pertussis adenylyl cyclase into neuroblastoma cells.
AB  - Bordetella pertussis produces a calmodulin-stimulated adenylyl cyclase that
      invades animal cells and raises intracellular cAMP levels [Confer, D. L., &
      Eaton, J. W. (1982) Science 217, 948-950; Shattuck, R. L., & Storm, D. R. (1985)
      Biochemistry 24, 6323-6328]. The mechanism for invasion of animal cells by this
      enzyme has not been defined, but there is considerable evidence that it does not
      enter by receptor-mediated endocytosis [Gordon, V. M., Leppla, S. H., & Hewlett,
      E. L. (1988) Infect. Immun. 56, 1066-1069; Donovan, M. G., & Storm, D. R. (1990)
      J. Cell. Physiol. 145, 444-449]. In this study, the importance of high-affinity
      calmodulin (CaM) binding for entry of the enzyme into neuroblastoma cells was
      evaluated using a mutant enzyme that has significantly lower affinity for
      calmodulin than the wild-type enzyme. Oligonucleotide-directed site-specific
      mutagenesis was used to create a point mutant at a critical tryptophan residue
      (Trp-242) within the proposed CaM binding domain of the B. pertussis adenylyl
      cyclase. Substitution of Trp-242 with Glu lowered the apparent affinity of the
      enzyme for calmodulin by 250-fold; however, the maximal enzyme activity in the
      presence of saturating calmodulin was equivalent to the wild-type enzyme. The Glu
      242 mutant adenylyl cyclase was returned to B. pertussis by homologous
      recombination, and the enzyme produced by this strain was examined for invasion
      of neuroblastoma cells. Although the mutant enzyme stimulated the production of
      intracellular cAMP in neuroblastoma cells, the rate of cAMP accumulation was at
      least 10-fold lower than that caused by the wild-type enzyme.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1390676
TI  - Site-directed mutagenesis of lysine 319 in the lactose permease of Escherichia
      coli.
AB  - Lys319, which is on the same face of putative helix X as His322 and Glu325 in the
      lactose permease of Escherichia coli, has been replaced with Leu by
      oligonucleotide-directed, site-specific mutagenesis. Although previous
      experiments suggested that the mutation does not alter permease activity, we
      report here that K319L permease is unable to catalyze active lactose accumulation
      or lactose efflux down a concentration gradient. The mutant does catalyze
      facilitated influx down a concentration gradient at a significant rate; however,
      the reaction occurs without concomitant H+ translocation. The mutant also
      catalyzes equilibrium exchange at about 50% of the wild-type rate, but it
      exhibits poor counterflow activity. Finally, flow dialysis and photoaffinity
      labeling experiments with p-nitrophenyl alpha-D-galactopyranoside indicate that
      K319L permease probably has a markedly decreased affinity for substrate. The
      alterations described are not due to diminished levels of the mutated protein in
      the membrane, since immunological studies reveal comparable amounts of permease
      in wild-type and K319L membranes. It is proposed that Lys319, like Arg302,
      His322, and Glu325, plays an important role in active lactose transport, as well
      as substrate recognition.

PMID- 1390677
TI  - Characterization of magnetically orientable bilayers in mixtures of
      dihexanoylphosphatidylcholine and dimyristoylphosphatidylcholine by solid-state
      NMR.
AB  - Mixtures of long-chain and short-chain phosphatidylcholine (PC) were
      characterized by multinuclear (13C, 31P, 2H) solid-state nuclear magnetic
      resonance. This work complements and extends previous characterization of such
      mixtures by focusing on concentrated mixtures at temperatures above the gel to
      liquid crystalline phase transition temperature (Tm) of the long-chain PC
      component. Above Tm it was observed that highly oriented, bilayer-like assemblies
      could be formed of mixtures of dimyristoylphosphatidylcholine (DMPC) and
      dihexanoylphosphatidylcholine (DHPC) in molar ratios ranging from approximately
      1:3.5 to 1:2 (DHPC:DMPC) over a considerable range of lipid concentrations (at
      least 3-40% w/v total lipid, for a 1:2.5 sample). Orientation was observed to
      occur only in an L alpha-like phase. The NMR data can be accounted for by a
      general model of the DHPC-DMPC aggregates in which DHPC can be found in two
      distinct populations (one highly ordered, one not). The averaged conformations of
      the glycerol backbone/headgroup regions of the long- and short-chain PC composing
      the assemblies were judged by solid-state 13C NMR to be similar to each other.
      The information gleaned about these mixtures and the quality of the oriented NMR
      spectra obtained suggest that DHPC-DMPC mixtures may prove to be useful as model
      membrane media in solid-state NMR studies of biomembranes.

PMID- 1390678
TI  - 1H NMR assignments and secondary structure of human beta 2-microglobulin in
      solution.
AB  - Sequence-specific resonance assignments of human beta 2-microglobulin (M(r)
      12,000) and its secondary structure are determined by 2D NMR techniques. The
      protein is found to contain two antiparallel beta-sheets each of four beta
      strands with the beta-sheets being connected by a single disulfide linkage. No
      evidence for any regular helical structure is found. Amide proton-solvent
      exchange rate constants and 3JHN alpha coupling constants are evaluated.

PMID- 1390679
TI  - Metabolic heterogeneity of carbon substrate utilization in mammalian heart: NMR
      determinations of mitochondrial versus cytosolic compartmentation.
AB  - Carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy can be used to
      target specific pathways of intermediary metabolism within intact tissues and was
      employed in this study to evaluate the compartmentation of pyruvate metabolism
      between the cytosol and mitochondrial matrix. The distribution of 13C into the
      tissue alanine, lactate, and glutamate pools was evaluated during metabolism of
      [3-13C]-pyruvate in intact, isolated perfused rabbit hearts with and without
      activation of pyruvate dehydrogenase activity by dichloroacetate (5 mM).
      Equilibrium between the intracellular alanine and pyruvate pools was in evidence
      from the rapid evolution of the steady-state 13C signal arising from the 3-carbon
      of alanine in intact hearts perfused with 2.5 mM 99.4% [3-13C]pyruvate. Augmented
      pyruvate oxidation, in response to perfusion with dichloroacetate, was evident
      within 13C NMR spectra of intact hearts as a relative increase in signal
      intensity of 53-62% (p less than 0.05) from the 4-carbon resonance of 13C
      enriched glutamate when compared to the unaffected alanine signal. The increased
      bulk flow of [3-13C]pyruvate into the tricarboxylic acid cycle in response to
      dichloroacetate resulted in elevated fractional enrichment of glutamate from 68%
      in controls to 83% in the treated group (p less than 0.04), via interconversion
      with alpha-ketoglutarate, without changes in the actual tissue content of
      glutamate. Evidence of metabolic heterogeneity of cytosolic and mitochondrial
      pyruvate pools was also obtained from analysis of tissue extracts with in vitro
      NMR spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390680
TI  - Conformation of parathyroid hormone: time-resolved fluorescence studies.
AB  - Conformational and environmental changes in the functionally significant amino
      terminal region of human parathyroid hormone (hPTH), induced by solvent or by
      complexation with acidic lipid, have been investigated. Structural perturbations
      were monitored by their effect on the fluorescence decay kinetics of the single
      tryptophyl residue at position 23. Data for the intact hormone were compared with
      those for its 1-34 and 13-34 analogues. Deletion of the 35-84 sequence had no
      significant effect on the structure of hPTH in the region of Trp-23, nor was
      there any evidence for interaction of this region with the 1-12 sequence. On the
      basis of a comparison of the results of this study with structural information
      available from other spectroscopic techniques, we propose that the local
      structure in the region of Trp-23 of aqueous solutions of hPTH and hPTH 1-34 has
      helical character. This local structure was not stable in aqueous hPTH 13-34, but
      was present in hPTH and its analogues, both on complexation with acidic lipid and
      in helix-promoting solvents. The tryptophyl fluorescence of the lipid-bound
      peptides was characteristic of an aqueous environment. Triple-exponential
      fluorescence decay kinetics were observed for the tryptophyl residue of hPTH and
      its deletion analogues. This can be explained in terms of ground-state
      heterogeneity due to the presence of three C alpha-C beta rotamers of the
      tryptophanyl indole side chain. Assuming this model, we show that the calculated
      fractional concentrations of the decay time components correlate with the likely
      rotamer populations and with their expected dependence on the main-chain
      conformation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390682
TI  - Determination of the site of phosphorylation of nodulin 26 by the calcium
      dependent protein kinase from soybean nodules.
AB  - Nodulin 26 is a nodule-specific protein that is associated with the symbiosome
      membrane of soybean root nodules. Nodulin 26 is an endogenous substrate for a
      novel calcium-dependent protein kinase (CDPK) of soybean root nodules. By
      phosphopeptide mapping of endoproteinase Lys-C-digested nodulin 26 and automated
      and manual peptide sequence analyses, we have identified the site on nodulin 26
      phosphorylated by CDPK. We have also established that the phosphorylation site of
      nodulin 26 is identical to the phosphorylation site of CK-15, a synthetic peptide
      with the carboxyl-terminal sequence of nodulin 26. The phosphorylation of nodulin
      26 occurs at position Ser262, and the phosphorylation of CK-15 occurs at the
      analogous position, Ser,6 in vitro. Thus, the CK-15 sequence apparently contains
      sufficient structural features of the phosphorylation site of nodulin 26 to be
      recognized by CDPK. On the basis of peptide mapping analysis of nodulin 26 from
      nodules that are metabolically labeled with [32P]phosphate, it appears that the
      site of nodulin 26 that is phosphorylated in vitro is also labeled in vivo. The
      data indicate that the carboxyl terminus of nodulin 26 is phosphorylated by CDPK
      and provide initial sequence data for the phosphorylation site of an endogenous
      substrate for a plant CDPK.

PMID- 1390681
TI  - Role of quinone-iron(III) interaction in NADPH-dependent enzymatic generation of
      hydroxyl radicals.
AB  - To study the effect of chelation of iron ions by quinones on the generation of OH
      radicals in biological redox systems, we have synthesized quinones that can form
      complexes with Fe(III) ions: 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12
      dione (Qbc) and 2-phenyl-4-(octylamino)naphtho[2,3-h]quinoline-7,12-dione (Qoc).
      A quinone with a similar structure without chelating group was synthesized as a
      control sample: 2-phenyl-5-nitronaphtho[2,3-g]indole-6,11-dione (Qn). Using
      optical spectroscopy, we determined the stability constant of Qbc with Fe(III)
      [Ks = (7 +/- 1) x 10(18) M-3] and the stoichiometry of the complex Fe(Qbc)3 in
      chloroform solutions. One-electron reduction potentials of Qbc, Qn, and
      adriamycin in dimethyl sulfoxide were measured by cyclic voltammetry. In the
      presence of Fe(III) the one-electron reduction potentials shifted toward positive
      values by 0.16 and 0.1 V for Qbc and adriamycin, respectively. Using the spin
      trap 5,5'-dimethyl-1-pyroline N-oxide (DMPO) and EPR, it was found that Qbc in
      the Fe(III) complex stimulated the formation of OH radicals in the enzymatic
      system consisting of NADPH and NADPH-cytochrome P-450 reductase more efficiently
      than adriamycin and quinone Qn. This is indicated by the absence of a lag period
      in the spin adduct appearance for Qbc and by a significantly higher rate of the
      spin adduct production, as well as by a larger absolute concentration of the spin
      adduct obtained for Qbc in comparison with Qn in the presence of
      Fe(III).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390683
TI  - Interdependency of the binding subsites in subtilisin.
AB  - Subtilisins are endopeptidases with an extended binding cleft comprising at least
      eight subsites, and kinetic studies have revealed that subsites distant from the
      scissile bond are important in determining the substrate preference of the
      enzymes. With the subtilisin enzyme Savinase, the interdependency of the
      individual Sn-Pn interactions has been investigated. It was found that the
      contributions from each subsite interaction to kcat/KM are not always additive.
      Such interdependency was also observed between subsites which are remote from
      each other. With a series of substrates covering S6 to S'4 of Savinase, it was
      observed that favorable amino acids in P1 or, more significantly, P4 of the
      substrate shield adverse effects of less favorable amino acids at other
      positions. Thus, an upper limit of kcat/KM was observed, suggesting a limit on
      the amount of substrate interaction energy which can be converted into transition
      state stabilization. Furthermore, with substrates in which all positions had been
      optimized, an upper limit of kcat/KM (approximately 2 x 10(9) min-1 M-1) was
      seen, both for a substrate with a high kcat and for one with a low KM. These
      results emphasize that the design of optimal substrates or substrate-derived
      inhibitors for endopeptidases preferably should be based on subsite mappings
      where interdependent substrate-subsite interactions have been eliminated.

PMID- 1390684
TI  - Active site similarities of glucose dehydrogenase, glucose oxidase, and
      glucoamylase probed by deoxygenated substrates.
AB  - The specificity constants, kcat/KM, were determined for glucose oxidase and
      glucose dehydrogenase using deoxy-D-glucose derivatives and for glucoamylase
      using deoxy-D-maltose derivatives as substrates. Transition-state interactions
      between the substrate intermediates and the enzymes were characterized by the
      observed kcat/Km values and found to be very similar. The binding energy
      contributions of individual sugar hydroxyl groups in the enzyme/substrate
      complexes were calculated using the relationship delta(delta G) = -RT ln
      [(kcat/KM)deoxy/(kcat/KM)hydroxyl] for the series of analogues. The activity of
      all three enzymes was found to depend heavily on the 4- and 6-OH groups (4'- and
      6'-OH in maltose), where changes in binding energies from 10 to 18 kJ/mol
      suggested strong hydrogen bonds between the enzymes and these substrate OH
      groups. The 3-OH (3'-OH in maltose) was involved in weaker interactions, while
      the 2-OH (2'-OH in maltose) had a very small if any role in transition-state
      binding. The three enzyme-substrate transition-state interactions were compared
      using linear free energy relationships (Withers, S. G., & Rupitz, K. (1990)
      Biochemistry 29, 6405-6409) in which the set of kcat/KM values obtained with
      substrate analogues for one enzyme is plotted against the corresponding values
      for a second enzyme. The high linear correlation coefficients (rho) obtained,
      0.916, 0.958, and 0.981, indicate significant similarity in transition-state
      interactions, although the three enzymes lack overall sequence homology.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390685
TI  - Affinity labeling of Cys111 of glutathione S-transferase, isoenzyme 1-1, by S-(4
      bromo-2,3-dioxobutyl)glutathione.
AB  - Incubation of S-(4-bromo-2,3-dioxobutyl)glutathione (S-BDB-G), a reactive
      analogue of glutathione, with the 1-1 isoenzyme of rat liver glutathione S
      transferase at pH 6.5 and 25 degrees C results in a time-dependent inactivation
      of the enzyme. k(obs) exhibits a nonlinear dependence on S-BDB-G from 50 to 1200
      microM, with a kmax of 0.111 min-1 and KI = 185 microM. The addition of 5 mM S
      hexylglutathione, a competitive inhibitor with respect to glutathione, gives
      almost complete protection against inactivation by S-BDB-G. About 1.2 mol of
      [3H]S-BDB-G/mol of enzyme subunit is incorporated when the enzyme is 85%
      inactivated, whereas 0.33 mol of reagent/mol of subunit is incorporated in the
      presence of S-hexylglutathione when the enzyme has lost only 17% of its original
      activity. Modified enzyme, prepared by incubating glutathione S-transferase with
      [3H]S-BDB-G in the absence or in the presence of S-hexylglutathione, was reduced
      with sodium borohydride, reacted with N-ethylmaleimide, and digested with alpha
      chymotrypsin. Analysis of the chymotryptic digests, fractionated by reverse-phase
      high-performance liquid chromatography, revealed Cys111 as the amino acid whose
      reaction with S-BDB-G correlates with enzyme inactivation. It is concluded that
      Cys111 lies within or near the hydrophobic substrate binding site of glutathione
      S-transferase, isoenzyme 1-1.

PMID- 1390686
TI  - Effects of cholesterol side-chain groups and adrenodoxin binding on the
      vibrational modes of carbon monoxide bound to cytochrome P-450scc: implications
      of the productive and nonproductive substrate bindings.
AB  - Effects of the bindings of cholesterol and its hydroxylated analogues on the Fe
      CO stretching and the C-O stretching vibrations of cytochrome P-450scc-CO complex
      were examined by resonance Raman and FT-IR spectroscopies to reveal the spatial
      relationship between the steroid side-chain groups and the heme-bound C-O moiety
      at the active center. These C-O and Fe-CO vibrations exhibited considerable
      variations depending on the steroids used; however, analyses on the nu Fe-CO vs
      nu C-O plot for cytochrome P-450scc indicated the absence of the negative
      correlation between these two vibrations, which is common among various Fe(2+)
      porphyrin-CO complexes having imidazole ligands. Rather, we noticed the existence
      of two groups depending on substrates, the one exhibiting C-O infrared absorption
      bands in the region from 1930 to 1940 cm-1 and higher enzymatic turnover numbers
      in the reconstituted enzymatic systems and the other exhibiting C-O infrared
      absorption bands in the region above 1945 cm-1 and lower enzymatic turnover
      numbers. Thus, the former substrate group is likely to be fitted into the
      substrate binding site in the efficient "productive substrate binding" structure,
      whereas the latter group may be bound to the enzyme in the structure not suitable
      for the efficient enzymatic reaction ("nonproductive substrate binding"
      conformation).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390687
TI  - Primary structure of an aliphatic nitrile-degrading enzyme, aliphatic nitrilase,
      from Rhodococcus rhodochrous K22 and expression of its gene and identification of
      its active site residue.
AB  - Peptides obtained by cleavage of a Rhodococcus rhodochrous K22 nitrilase, which
      acts on aliphatic nitriles such as acrylonitrile, crotonitrile, and
      glutaronitrile, have been sequenced. The data allowed the design of
      oligonucleotide probes which were used to clone a nitrilase encoding gene.
      Plasmid pNK21, in which 2.05-kb sequence covering the region encoding the
      nitrilase was was placed under the control of the lac promoter, directed
      overproduction of enzymatically active nitrilase in response to addition of
      isopropyl beta-D-thiogalactopyranoside in Escherichia coli. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of the cell extract showed that the
      amount of nitrilase was about 40% of the total soluble proteins, leading to the
      establishment of a simple purification of the nitrilase. The nucleotide sequence
      of the nitrilase gene predicts a protein composed of 383 amino acids (M(r) =
      42,275), including only one cysteine. The amino acid sequence homology between
      the Rhodococcus nitrilase and the Klebsiella ozaenae bromoxynil nitrilase
      [Stalker et al. (1988) J. Biol. Chem. 263, 6310-6314] was 38.3%, and a unique
      cysteinyl residue (Cys-170) in the former nitrilase was conserved at the
      corresponding position in the latter nitrilase. Cys-170 of the Rhodococcus
      nitrilase was replaced by Ala or Ser by site-directed mutagenesis. Both mutations
      resulted in the complete loss of nitrilase activity, clearly indicating that this
      cysteinyl residue is essential for the catalytic activity.

PMID- 1390688
TI  - Nature of the interaction of growth factors with suramin.
AB  - Suramin inhibits the binding of a variety of growth factors to their cell surface
      receptors. The direct interaction of suramin with acidic fibroblast growth factor
      has been detected by the enhancement of the drug's fluorescence in the presence
      of the protein with the maximum effect occurring at a molar ratio of suramin to
      aFGF of 2:1. This interaction stabilizes aFGF to thermal denaturation and
      partially protects a free thiol in its polyanion binding site from oxidation. The
      binding of suramin to aFGF also induces aggregation of the growth factor to at
      least a hexameric state as detected by static and dynamic light scattering as
      well as by gel filtration studies. Both CD and amide I' FTIR spectra of aFGF in
      the presence and absence of suramin suggest that the drug may also be causing a
      small conformational change in the growth factor. Suramin produces an even
      greater aggregation of bFGF and PDGF but not of EGF or IGF-1. Evidence for a
      suramin-induced conformational change in IGF-1 but not EGF is found by CD,
      however. It is concluded that suramin binds to many growth factors and that this
      induces microaggregation and, in some cases, conformational changes. In the case
      of aFGF, suramin interacts at or near its heparin binding site. The relationship
      between these phenomena and the anti-growth factor activity of suramin remains to
      be clearly elucidated.

PMID- 1390689
TI  - Inhibition of protein kinase C by cationic amphiphiles.
AB  - A large number of PKC inhibitors are positively charged. We evaluated the
      structural features of cationic amphiphiles which are necessary for inhibiting
      PKC. Many of these compounds were derivatives of cholesterol, which possesses a
      hydrophobic backbone which does not perturb hydrocarbon packing in membrane
      bilayers. In addition, they contain a tertiary or quaternary nitrogen
      functionality in the head group. All designed cholesterol-based amphiphiles
      inhibit PKC activity; the potency of the amphiphile correlates with the presence
      of positive charge. Quaternary ammonium amphiphiles are 10-fold more potent than
      their tertiary amine counterparts, generally inhibiting in the 10-60 microM range
      using the Triton mixed micelle assay. Aside from charge, factors such as the
      structure of the amine-containing head group, its length from the hydrocarbon
      moiety, or the number of amine groups on the amphiphile did not markedly
      influence inhibitor potency. In contrast, the hydrocarbon backbone did influence
      potency: cationic amphiphiles containing a steroid backbone were more potent
      inhibitors of PKC than their straight-chain analogues. Changing the nature of the
      hydrocarbon from a sterol to an alkyl group lowers the pK of the amine head group
      so that the straight-chain analogues are no longer cationic in the conditions in
      the PKC assay. The results of these studies suggest that a combination of
      positive charge and a bilayer-stabilizing structural characteristic provides a
      basis for the rational design of PKC inhibitors.

PMID- 1390690
TI  - Determinants of high-affinity DNA binding by the glucocorticoid receptor:
      evaluation of receptor domains outside the DNA-binding domain.
AB  - In this study, we have investigated the influence of regions outside the DNA
      binding domain of the human glucocorticoid receptor on high-affinity DNA binding.
      We find that the DNA-binding domain shows a 10-fold lower affinity for a
      palindromic DNA-binding site than the intact receptor. The N-terminal part of the
      receptor protein does not influence its DNA-binding affinity, while the C
      terminal steroid-binding domain increases the DNA-binding affinity of the
      receptor molecule. It has previously been shown that both the intact
      glucocorticoid receptor and the glucocorticoid receptor DNA-binding domain bind
      to a palindromic glucocorticoid response element on DNA as dimers. It is likely
      that differences in DNA-binding affinity observed result from protein-protein
      interactions outside the DNA-binding domain between receptor monomers, as has
      been shown for the estrogen receptor. We have previously identified a segment
      involved in protein-protein interactions between DNA-binding domains of
      glucocorticoid receptors. This, in combination with results presented in this
      study, suggests that there are at least two sites of contact between receptor
      monomers bound to DNA. We suggest that the interaction between the DNA-binding
      domains may act primarily to restrict DNA binding to binding sites with
      appropriate half-site spacing and that additional stability of the receptor dimer
      is provided by the interactions between the steroid-binding domains.

PMID- 1390691
TI  - Microstructural polymorphism in bovine brain galactocerebroside and its two major
      subfractions.
AB  - Aqueous suspensions of either brain galactocerebrosides or its subfraction
      consisting of alpha-hydroxyacyl galactocerebrosides are mainly composed of
      vesicles or granular lipid with occasional multilamellar sheets. In aqueous media
      the other subfraction consisting of non-hydroxyacyl galactocerebrosides forms
      some helical structures, but most of the lipid remains as granules or vesicles.
      It is demonstrated that thermal cycling of non-hydroxyacyl galactocerebrosides in
      polar nonaqueous solvents can greatly enhance the degree of conversion to helical
      ribbons about 100 nm in diameter. These structures appear to be a stable
      dehydrated crystalline form of this lipid and are morphologically similar to
      helical microstructures produced by a few synthetic lipids. On the other hand,
      similar treatment of unfractionated bovine brain cerebroside and its alpha
      hydroxy fatty acyl subfraction quantitatively produces straight needles that
      appear to be cochleate cylinders. While their dimensions depend on formation
      conditions, a typical suspension has uniform particles with diameters close to
      100 nm and lengths variable from one to a few hundred micrometers. This is the
      first report demonstrating the quantitative formation of crystalline high axial
      ratio microstructures from complex mixtures of natural lipids. The different
      microstructures formed by the two components appear related to the various forms
      of lipid deposits occurring in lipid storage diseases. The similarity of these
      "synthetic" microstructures to biological structures in which they are found
      (such as myelin and intestinal brush border microvilli) strengthens the
      possibility that galactocerebrosides have a role in stabilizing cylindrical
      biological structures.

PMID- 1390692
TI  - Promotion of the release of 11-cis-retinal from cultured retinal pigment
      epithelium by interphotoreceptor retinoid-binding protein.
AB  - This study investigates whether the interphotoreceptor retinoid-binding protein
      (IRBP) is necessary for the release of 11-cis-retinaldehyde (RAL) or if the
      retinoid is constitutively released from the retinal pigment epithelium (RPE)
      following synthesis. The strategic location of IRBP in the interphotoreceptor
      matrix (IPM) and its retinoid-binding ability make it a candidate for a role in
      11-cis-RAL release. Fetal bovine RPE cells were grown in permeable chambers, and
      their apical surfaces were incubated with medium containing either apo-IRBP, the
      apo form of cellular retinaldehyde-binding protein (CRALBP), the apo form of
      serum retinol-binding protein (RBP), or bovine serum albumin (BSA) or with medium
      devoid of binding proteins. [3H]-all-trans-Retinol (ROL) was delivered to the
      basal surface of the cells by RBP. High-performance liquid chromatography
      demonstrated that [3H]-11-cis-RAL was optimally released into the apical medium
      when apo-IRBP was present. The most surprising result was the diminished level of
      [3H]-11-cis-RAL when apo-CRALBP was in the apical medium. Circular dichroism
      demonstrated that CRALBP had not been denatured by the photobleaching required
      for endogenous ligand removal. Therefore, apo-CRALBP should have been able to
      bind [3H]-11-cis-RAL if it was constitutively released into the apical medium. In
      addition, when proteins other than apo-IRBP were present, or if the cells were
      incubated with medium alone, the observed decrease in apical [3H]-11-cis-RAL was
      concomitant with a buildup of intracellular [3H]-all-trans-retinyl palmitate and
      [3H]-all-trans-ROL in the basal culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390693
TI  - Characterization of the protonation and hydrogen bonding state of the histidine
      residues in IIAmtl, a domain of the phosphoenolpyruvate-dependent mannitol
      specific transport protein.
AB  - The A domain of the mannitol-specific EII, IIAmtl, was subcloned and proven to be
      functional in the isolated form (Van Weeghel et al., 1991). It contains a
      histidine phosphorylation site, the first of two phosphorylation sites in the
      parent protein. In this paper, we describe the characterization of the three
      histidine residues in IIAmtl with respect to their protonation and hydrogen
      bonding state, using 1H[15N] heteronuclear NMR techniques and protein selectively
      enriched with [delta 1,epsilon 2-15N]histidine. The active site residue has a low
      pKa (less than 5.8) and shows no hydrogen bond interactions. The proton in the
      neutral ring is located at the N epsilon 2 position, which also proved to be the
      site of phosphorylation. The phosphorylation raises the pKa of the active site
      histidine considerably but does not change the hydrogen bond situation. The other
      two histidine residues, one of which is probably located on the surface of the
      protein, were also characterized. Both show hydrogen bond interactions in the
      unphosphorylated protein, but these are disturbed by the phosphorylation process.
      These observations, combined with small changes in pKa and titration behavior,
      indicate that the IIAmtl changes its conformation upon phosphorylation.

PMID- 1390694
TI  - In vivo and in vitro activities of point mutants of the bacteriophage T7 RNA
      polymerase promoter.
AB  - Two compatible plasmids were recently reported [Ikeda et al. (1992) Nucleic Acids
      Res. 20, 2517-2524] that together can be used to determine whether a mutant T7
      RNA polymerase promoter is active or inactive in vivo. The first plasmid, pKGP1
      1, carries T7 gene 1 (the gene encoding T7 RNA polymerase) ligated to a tac
      promoter, while the second plasmid, pCM-X#, carries the gene encoding
      chloramphenicol acetyltransferase (CAT) ligated to potential T7 promoters. If the
      pCM-X# plasmid carries a potential T7 promoter that can be utilized by T7 RNA
      polymerase, then CAT is produced from transcripts generated by T7 RNA polymerase
      from the potential promoter on the pCM-X# plasmid. To determine whether
      Escherichia coli growth characteristics and chloramphenicol (cam) resistance
      produced by the plasmids pKGP1-1 and pCM-X# reflect the T7 promoter activity of
      the possible promoters carried by the pCM-X# plasmids, the in vivo and in vitro
      strengths of the potential T7 promoters were compared and correlated. In vivo
      promoter strength was determined by measuring the relative amounts of CAT present
      in E. coli extracts, while relative in vitro promoter strength was measured in
      transcription assays. The in vivo and in vitro strengths of 22 point mutants of
      the consensus T7 promoter were shown to correlate with the growth characteristics
      and cam resistance conferred to E. coli harboring the plasmid pKGP1-1 and the
      respective pCM-X# plasmid.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390695
TI  - Mismatch-induced switch of neocarzinostatin attack sites in the DNA minor groove.
AB  - Based on the finding that the wobble G.T mismatch 5' to the C of AGC.GCT results
      in switching of the attack chemistry by neocarzinostatin chromophore (NCS-Chrom)
      on the deoxyribose moiety of C from C-1' to C-4' [Kappen, L. S. & Goldberg, I. H.
      (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 6706-6710], a series of mismatches has
      been explored for their effect on the chemistry of damage at the T of AGT.ACT in
      oligodeoxynucleotides, a site at which 4'-chemistry ordinarily occurs. Placement
      of a G.T mispair 5' to the T results in a marked increase in 4'-chemistry, as
      measured by the formation of breaks with 3'-phosphoglycolate ends and abasic
      sites due to 4'-hydroxylation. Strikingly, 4'-chemistry is induced at the T on
      the complementary strand, a site ordinarily restricted to 5'-chemistry.
      Substitution of dioxygen by the radiation sensitizer misonidazole exerts a
      pronounced effect on the partitioning of the 4'-chemistry in favor of the 3'
      phosphoglycolate product. Both stable T.G and unstable T.C mismatches at the
      attack site itself are associated with marked inhibition of damage at this site.
      Whereas placement of the relatively stable G.A mismatch on the 5'-side of the T
      residue (AGT) results in substantial inhibition of damage at the T without
      shifting of chemistry, the same mismatch at the 3'-side of the attack site
      decreases damage only slightly but is associated with the appearance of
      significant 1'-chemistry. By contrast, no shift in chemistry is found with
      bleomycin, which attacks at C-4'.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390696
TI  - An NMR investigation of the changes in plasma membrane triglyceride and
      phospholipid precursors during the activation of T-lymphocytes.
AB  - Two-dimensional 1H-NMR spectroscopy was used to quantify the level of
      isotropically tumbling plasma membrane triglyceride and the intracellular
      concentrations of water-soluble phospholipid precursors during the activation of
      thymic T-lymphocytes. The concentration of "mobile" triglyceride in the plasma
      membrane was seen to increase 25-fold during 72 h of activation of murine thymic
      T-lymphocytes with ionomycin and phorbol myristate acetate. This is the first
      unequivocal demonstration of such a dramatic increase in mobile plasma membrane
      triglyceride during T-lymphocyte activation and leads to the suggestion that
      immune cell activation is associated with increased plasma membrane fluidity. The
      intracellular concentrations of choline- and ethanolamine-based phospholipid
      precursors were shown to increase during the early stages of T-lymphocyte
      activation and then remain at levels above those in resting cells. This may
      facilitate de novo phospholipid biosynthesis, which is presumably necessary since
      cell volume, and hence the plasma membrane surface area, was demonstrated to
      increase significantly during thymocyte activation.

PMID- 1390697
TI  - Investigation of the mechanism and steric course of the reaction catalyzed by 6
      methylsalicylic acid synthase from Penicillium patulum using (R)-[1-13C;2-2H]-
      and (S)-[1-13C;2-2H]malonates.
AB  - Chiral malonyl-CoA derivatives, enzymically synthesized from (R)- and (S)-[1
      13C;2-2H]malonates using succinyl-CoA transferase, were incorporated into 6
      methylsalicylic acid with homogeneous 6-methylsalicylic acid synthase isolated
      from Penicillium patulum. Analysis of the 6-methylsalicylic acid formed
      established that the hydrogen atoms at the 3- and 5-positions are derived from
      opposite absolute configurations in malonyl-CoA. When acetoacetyl-CoA was used as
      the starter molecule, a single hydrogen atom is incorporated from the chiral
      malonates into the 3-position of the 6-methylsalicylic acid. Mass spectrometric
      analysis of the 6-methylsalicylic acid indicates that this hydrogen atom
      originates from HRe of malonyl-CoA or HSi in the polyketide intermediate. It is
      thus concluded that the hydrogen atom at the 5-position of 6-methylsalicylic acid
      originates from HSi of malonyl-CoA or HRe in the polyketide intermediate. During
      the reaction the enzyme also catalyzes the stereospecific exchange of hydrogen
      atoms in the polyketide intermediates. The implications of the stereochemical
      information from these experiments are discussed in relation to the mechanism of
      the 6-methylsalicylic acid synthase reaction.

PMID- 1390699
TI  - Forces, bond lengths, and reactivity: fundamental insight into the mechanism of
      enzyme catalysis.
AB  - Comparison of spectroscopic, kinetic, and thermodynamic data for a series of
      functioning acylserine proteases suggests that the observed variation in
      deacylation rates can be accounted for by changes in the properties of the acyl
      enzyme's ground state. The acyl-enzyme's catalytically crucial acyl carbonyl
      group is probed by resonance Raman spectroscopy. Its spectral frequency is used
      to gauge both the carbonyl bond length and the strength of hydrogen bonding
      (originating from groups making up the oxyanion hole) to the carbonyl oxygen
      atom. As the deacylation rate increases 16,300-fold through the series, a shift
      in carbonyl frequency, vC = O, of -54 cm-1 corresponds to a carbonyl bond length
      increase of 0.025 A. The decrease in vC = O is also consistent with an increase
      in hydrogen bond donor enthalpy of -27 kJ mol-1. Interestingly, this value
      resembles closely the decrease in activation energy for deacylation through the
      series, 24 kJ mol-1, demonstrating that the hydrogen bonds to the carbonyl oxygen
      atom can provide sufficient energy to account for the observed rate
      accelerations.

PMID- 1390698
TI  - Selective abstraction of 2H from C-1' of the C residue in AGC.ICT by the radical
      center at C-2 of activated neocarzinostatin chromophore: structure of the
      drug/DNA complex responsible for bistranded lesion formation.
AB  - Glutathione-activated neocarzinostatin chromophore (NCS-Chrom) generates
      bistranded lesions at AGC.GCT sequences in DNA, consisting of an abasic site at
      the C residue and a strand break at the T residue on the complementary strand,
      due to hydrogen atom abstraction from C-1' and C-5', respectively. Earlier work
      showed that 2H from C-5' of T was selectively abstracted by the radical center at
      C-6 of activated NCS-Chrom, supporting a proposed model of the active-drug/DNA
      complex. However, since under the conditions used breaks at the T exceeded their
      inclusion in bistranded lesions, it was not clear what fraction of the hydrogen
      transfer represented bistranded lesions. Since virtually all abasic sites at the
      C are part of a bistranded lesions, hydrogen transfer from C-1' of C into the
      drug should reflect only the bistranded reaction. Accordingly, a self
      complementary oligodeoxynucleotide 5'-GCAGCICTGC-3' was synthesized in which the
      C contained 2H at the C-1' position. In order to eliminate an 2H isotope effect
      on the transfer and to increase the extent of the bistranded reaction, an I
      residue was substituted for the G opposite the C residue. Sequencing gel
      electrophoretic analysis revealed that under one-hit kinetics, 37% of the damage
      reaction was associated with abasic site (alkali-labile break) formation at the C
      residue and 48% with direct strand breaks at the T residue. Thus, 74% of the
      damage involved a bistranded lesion. 1H NMR spectroscopic analysis of the reacted
      chromophore showed that 2H had been selectively transferred into the C-2 position
      to the extent of approximately 22%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390700
TI  - Conformationally restricted thrombin inhibitors resistant to proteolytic
      digestion.
AB  - A new type of thrombin exo-site inhibitor has been designed with enhanced
      inhibitory potency and increased metabolic stability. With the aid of the model
      of the structure of the thrombin-hirudin fragment complex [Yue, S.-Y., DiMaio,
      J., Szewczuk, Z., Purisima, E. O., Ni, F., & Konishi, Y. (1992) Protein Eng. 5,
      77-85], cyclic analogs of the hirudin fragment (hirudin55-65) were designed and
      synthesized. In these analogs, the side chains of appropriately substituted
      residues, 58 and 61, were joined in order to restrict the conformation of the
      inhibitor. An analog with an 18-membered lactam ring showed higher antithrombin
      activity (IC50 = 0.57 microM) than the corresponding analogs with 17- or 16
      membered rings and was 2-fold more potent than its linear counterpart. Even 4
      fold greater enhancement was obtained when a shorter fragment, hirudin 55-62, was
      cyclized. This cyclization not only improved the potency but, more importantly,
      dramatically increased the resistance to proteolytic digestion. Remarkable
      enhancement of stability to proteolysis was observed for peptide bonds located in
      the exocyclic linear peptide segments. These results are discussed using
      molecular modeling.

PMID- 1390701
TI  - Allosteric modifiers of hemoglobin: 2-[4-[[(3,5-disubstituted
      anilino)carbonyl]methyl]phenoxy]-2-methylpropionic acid derivatives that lower
      the oxygen affinity of hemoglobin in red cell suspensions, in whole blood, and in
      vivo in rats.
AB  - Two new potent allosteric effectors of hemoglobin, RSR-4 [2-[4-[[(3,5
      dichloroanilino)carbonyl]-methyl]phenoxy]-2- methylpropionic acid] and RSR-13 [2
      [4-[[(3,5-dimethlanilino)carbonyl]methyl]-phenoxy]-2-methylp rop ionic, are
      compared to the previously reported compounds L3,5 and L3,4,5 [Lalezari, I.,
      Lalezari, P., Poyart, C., Marden, M., Kister, J., Bohn, B., Fermi, G., & Perutz,
      M. F. (1990) Biochemistry 29, 1515]. Unlike L3,5 and L3,4,5, RSR-4 and RSR-13 are
      less impeded by physiological concentrations of serum albumin. RSR-4 has also
      been shown to be more effective than L3,5 in shifting the allosteric equilibrium
      of bovine Hb toward the low-affinity T-state. X-ray crystal studies show that
      both RSR-4 and RSR-13 bind to only one pair of symmetry-related sites in the Hb
      central water cavity whereas previous studies on L3,5 and L3,4,5 demonstrated a
      second pair of symmetry-related binding sites near Arg 104 beta. Three major
      interactions between these allosteric effectors and Hb include the acid group
      with the guanidinium group of C-terminal Arg 141 alpha, the effector's amide
      oxygen with the ammonium ion of Lys 99 alpha, and the phi electrons of the
      halogenated or methylated aromatic ring and Asn 108 beta. No explanation has been
      found for the difference in number of binding sites observed for RSR-4 and RSR-13
      (two sites) compared to L3,5 and L3,4,5 (four sites); also no correlation has
      been made between the number of binding sites and degree of allosteric shift in
      the oxygen equilibrium curve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390702
TI  - H NMR investigation of the influence of interacting sites on the dynamics and
      thermodynamics of substrate and ligand binding to horseradish peroxidase.
AB  - The influence of substrate benzhydroxamic acid (BHA) and iron ligand (cyanide) on
      the thermodynamics and dynamics of each of the two binding sites of horseradish
      peroxidase (HRP) isozyme C has been investigated by 1H NMR spectroscopy. A
      combination of line-width analysis and saturation transfer spectroscopy has
      allowed the direct determination of the off-rate of substrate and ligand in the
      absence or presence of the other. These off-rates, together with available
      dissociation constants obtained by optical spectroscopy (Schonbaum, 1973),
      provide estimates for kon. The dissociation constant for cyanide binding to the
      BHA.HRP complex was also directly determined by NMR. In all cases the 1H NMR
      determined dynamic and thermodynamic data agree well with those values available
      in the literature. BHA binding leads to a 200-fold decrease in CN- affinity that
      arises from a factor greater than 10 decrease in koff(CN-) and greater than 2 x
      10(3) decrease in kon(CN-). While a portion of the decrease in kon(CN-) can be
      rationalized by water coordination of the iron in the BHA.HRP complex, the
      additional decrease in kon(CN-) and that in koff(CN-) indicates that BHA in the
      binding pocket blocks the CN- ligation channel and serves as a "gate" to CN-
      exchange. This view is supported by observing a factor greater than 4 decrease in
      distal His labile proton exchange with bulk water in HRP-CN upon BHA binding. The
      ternary complex BHA.HRP-CN is shown to be heterogeneous. While the thermodynamics
      of BHA and CN- binding appear similar in the two ternary complexes, the BHA on-
      and off-rates for the two complexes differ by a factor of approximately 10. The
      two heterogeneous forms interconvert at 25 degrees C at approximately 2 x 10(2) s
      1, precluding the determination of any difference in the CN- binding rates by
      saturation transfer. The greater lability of one of the two ternary complexes is
      attributed to an alternate orientation of some distal residue that blocks the
      substrate binding channel in one of the forms. Transferred nuclear Overhauser
      effects from the heme to BHA in the ternary complex reveal that the BHA substrate
      is in contact not only with the heme pyrrole D substituents but also with the
      distal His 42, indicating that the polar side chain of BHA extends well into the
      distal heme pocket.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1390703
TI  - Secondary structure and orientation of the surfactant protein SP-B in a lipid
      environment. A Fourier transform infrared spectroscopy study.
AB  - Attenuated total reflection Fourier transform infrared spectroscopy was used to
      investigate the secondary structure of the surfactant protein SP-B. Nearly half
      of the polypeptide chain is folded in an alpha-helical conformation. No
      significant change of the secondary structure content was observed when the
      protein is associated to a lipid bilayer of dipalmitoylphosphatidylcholine
      (DPPC)/phosphatidylglycerol (PG) or of dipalmitoylphosphatidylglycerol (DPPG).
      The parameters related to the gamma w(CH2) vibration of the saturated acyl chains
      reveal no modification of the conformation or orientation of the lipids in the
      presence of SP-B. A model of orientation of the protein at the lipid/water
      interface is proposed. In this model, electrostatic interactions between charged
      residues of SP-B and polar headgroups of PG, and the presence of small
      hydrophobic alpha-helical peptide stretches slightly inside the bilayers, would
      maintain SP-B at the membrane surface.

PMID- 1390704
TI  - Conformation of a pentacosapeptide representing the RNA-binding N-terminus of
      cowpea chlorotic mottle virus coat protein in the presence of oligophosphates: a
      two-dimensional proton nuclear magnetic resonance and distance geometry study.
AB  - Conformational studies were performed on a synthetic pentacosapeptide
      representing the RNA-binding N-terminal region of the coat protein of cowpea
      chlorotic mottle virus. Two-dimensional proton NMR experiments were performed on
      the highly positively charged peptide containing six arginines and three lysines
      in the presence of an excess of monophosphates, tetra(poly)phosphates, or
      octadeca(poly)phosphates mimicking the phosphates of the RNA. The results show
      that the peptide alternates between various extended and helical structures in
      the presence of monophosphate and that this equilibrium shifts toward the helical
      structures (with the helical region situated between residues 10 and 20) in the
      presence of oligophosphates. Distance geometry calculations using distance
      constraints derived from a NOESY spectrum of the peptide in the presence of
      tetra(poly)phosphate resulted in eight structures belonging to two structure
      families. The first family consists of five structures with an alpha-helixlike
      conformation in the middle of the peptide, and the second family consists of
      three structures with a more open conformation. The propensity to form an alpha
      helical conformation in the N-terminal part of this viral coat protein upon
      binding of phosphate groups to the positively charged side chains is suggested to
      play an essential role in RNA binding.

PMID- 1390706
TI  - Triple-helix formation by an oligonucleotide containing one (dA)12 and two (dT)12
      sequences bridged by two hexaethylene glycol chains.
AB  - The triple-helix formation by the oligonucleotide (dA)12-x-(dT)12-x-(dT)12, where
      x is a hexaethylene glycol group, was investigated by thermal denaturation
      analysis and circular dichroism spectroscopy. Thermal denaturation analysis
      showed that this single-stranded oligonucleotide is able to fold back on itself
      twice to give a triple helix at low temperature. Upon an increase in the
      temperature, two cooperative transitions were observed: formation of a double
      stranded structure with a dangling x-(dT)12 extremity, then formation of a single
      stranded coil structure. Due to the intramolecular character of the transition,
      the triplex is much more stable than that formed by the reference mixture (dA)12
      + 2(dT)12. In 0.1 M NaCl, the triplex-to-coil transition occurred at about 30
      degrees C whereas the duplex-to-coil was at about 60 degrees C. Upon an increase
      in the salt, the increase of temperature corresponding to the triplex-to-duplex
      transition was larger than that of the duplex-to-coil transition. MgCl2 showed
      higher efficiency than NaCl to promote triplex or duplex formation. The
      thermodynamic parameters delta H and delta S were determined at various ionic
      strengths for both transitions. Both the enthalpy change and entropy change
      associated with triplex-to-duplex transition (Hoogsteen base pairing) were
      smaller than those associated to the duplex-to-coil transition (Watson-Crick base
      pairing). When the ionic strength increased, the parameters -delta H and -delta S
      showed a very small decrease for the duplex-to-coil transition whereas a strong
      increase was observed with the triplex-to-duplex transition.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1390705
TI  - Specific valylation of turnip yellow mosaic virus RNA by wheat germ valyl-tRNA
      synthetase determined by three anticodon loop nucleotides.
AB  - The valylation by wheat germ valyl-tRNA synthetase of anticodon loop mutants of
      turnip yellow mosaic virus RNA has been studied. RNA substrates 264 nucleotides
      long were made by T7 RNA polymerase from cDNA encompassing the 3' tRNA-like
      region of genomic RNA. Substitution singly, or in combination, of three
      nucleotides in the anticodon loop resulted in very poor valylation (Vmax/KM less
      than 10(-3) relative to wild type). These nucleotides thus represent the major
      valine identity determinants recognized by wheat germ valyl-tRNA synthetase;
      their relative contribution to valine identity, in descending order, was as
      follows: the middle nucleotide of the anticodon (A56 in TYMV RNA), the 3'
      anticodon nucleotide (C55), and the 3'-most anticodon loop nucleotide (C53).
      Substitutions in the wobble position (C57) had no significant effect on
      valylation kinetics, while substitutions of the discriminator base (A4) resulted
      in small decreases in Vmax/Km. Mutations in the major identity nucleotides
      resulted in large increases in KM, suggesting that wheat germ valyl-tRNA
      synthetase has a lowered affinity for variant substrates with low valine
      identity. Comparison with other studies using valyl-tRNA synthetases from
      Escherichia coli and yeast indicates that the anticodon has been phylogenetically
      conserved as the dominant valine identity region, while the identity contribution
      of the discriminator base has been less conserved. The mechanism by which
      anticodon mutations are discriminated also appears to vary, being affinity-based
      for the wheat germ enzyme, and kinetically-based for the yeast enzyme [Florentz
      et al. (1991) Eur. J. Biochem. 195, 229-234].

PMID- 1390707
TI  - Role of individual histone tyrosines in the formation of the nucleosome complex.
AB  - We have determined the accessibility of histone tyrosine residues to react with p
      nitrobenzenesulfonyl fluoride (NBSF) in intact nuclei, salt-dissociated
      nucleosomes, isolated histone complexes, and individual core histones. Of the 15
      core histone tyrosine residues, 13 are inaccessible in native nucleosomes; only
      Tyr121 near the C-terminus of H2B is fully accessible, and Tyr54 of H3 is
      partially accessible under near-physiological conditions. When H1 and the basic N
      terminal tails of the core histones are dissociated from the DNA by treating
      nuclei with 0.4 and 0.8 M NaCl, the two tyrosines which are adjacent to the basic
      regions of H2B and H3 become accessible as well. This indicates that these
      tyrosine residues may be involved in histone-DNA interactions, either directly or
      indirectly. When the H2A-H2B dimers are dissociated from the chromatin by raising
      the NaCl concentration to 1.2 M, three to four tyrosines located in the
      structured regions of H2B and H4 are exposed, suggesting that these tyrosine
      residues may be located at the dimer-tetramer interface. Dissociating all the
      histones from the DNA at an even higher ionic strength as a mixture of dimers,
      tetramers, and octamers does not change the pattern of Tyr exposure, but reduces
      the reactivity of the tyrosines at the dimer-tetramer interface as would be
      expected from the reassociation of H2A-H2B dimers and H3-H4 tetramers.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1390708
TI  - Dissection of the functional role of structural elements of tyrosine-63 in the
      catalytic action of human lysozyme.
AB  - The functional role of tyrosine-63 in the catalytic action of human lysozyme (EC
      3.2.1.17) has been probed by site-directed mutagenesis. In order to identify the
      role of Tyr63 in the interaction with substrate, both the three-dimensional
      structures and the enzymatic functions of the mutants, in which Tyr63 was
      converted to phenylalanine, tryptophan, leucine, or alanine, have been
      characterized in comparison with those of the wild-type enzyme. X-ray
      crystallographical analysis of the mutant enzyme at not less than 1.77-A
      resolution indicated no remarkable change in tertiary structure except the side
      chain of 63rd residue. The conversion of Tyr63 to Phe or Trp did not change the
      enzymatic properties against the noncharged substrate (or substrate analogs)
      largely, while the conversion to Leu or Ala markedly reduced the catalytic
      activity to a few percent of wild-type enzyme. Kinetic analysis using p
      nitrophenyl penta-N-acetyl-beta-(1----4)-chitopentaoside (PNP-(GlcNAc)5) as a
      substrate revealed that the reduction of activity should mainly be attributed to
      the reduction of affinity between enzyme and substrate. The apparent contribution
      of the phenolic hydroxyl group and the phenol group in the side chain of Tyr63
      was estimated to 0.4 +/- 0.4 and 2.5 +/- 0.8 kcal mol-1, respectively. The result
      suggested that the direct contact between the planar side-chain group of Tyr63
      and the sugar residue at subsite B is a major determinant of binding specificity
      toward a electrostatically neutral substrate in the catalytic action of human
      lysozyme.

PMID- 1390709
TI  - Role of residue 478 as a determinant of the substrate specificity of cytochrome
      P450 2B1.
AB  - Two allelic variants and eight site-directed mutants of cytochrome P450 2B1
      differing at residue 478 have been expressed in COS cells and assayed for
      androstenedione hydroxylase activities. The 478Gly and 478Ala variants and five
      mutants (Ser, Thr, Val, Ile, and Leu) exhibited 16 beta-OH:16 alpha-OH ratios
      ranging from 0.7 to 9.3, whereas the Pro, Glu, and Arg mutants were expressed but
      inactive. The seven samples active toward androstenedione also exhibited
      testosterone 16 beta-OH:16 alpha-OH ratios ranging from 0.4 to 2.3. With both
      steroids, the Gly variant had the highest 16 beta-hydroxylase activity, and the
      16 beta-OH:16 alpha-OH ratio increased with the size of aliphatic size chains
      (Ala, Val, and Ile/Leu). The highest ratio of androgen 15 alpha:16-hydroxylation
      was observed with the Ser mutant. On the basis of previous work indicating
      decreased susceptibility of the 478Ala variant in liver microsomal and
      reconstituted systems to inactivation by chloramphenicol analogs, methodology was
      refined for monitoring enzyme inactivation in COS cell microsomes. The Gly and
      Ala variants were inactivated by chloramphenicol with similar rate constants,
      whereas the Ser and Val mutants were inactivated more slowly, and the Leu mutant
      was refractory. Only the Gly variant was inactivated by the chloramphenicol
      analog N-(2-p-nitrophenethyl)chlorofluoroacetamide. Thus, the side chain of
      residue 478 appears to be a major determinant of enzyme inactivation as well as
      of androgen hydroxylation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390710
TI  - Site-directed mutagenesis identifies catalytic residues in the active site of
      Escherichia coli phosphofructokinase.
AB  - Six active site mutants of Escherichia coli phosphofructokinase have been
      constructed and characterized using steady-state kinetics. All but one of the
      mutants (ES222) have significantly lower maximal activity, implicating these
      residues in the catalytic process. Replacement of Asp127, the key catalytic
      residue in the forward reaction with Glu, results in an enzyme with wild-type
      cooperative and allosteric behavior but severely decreased Fru6P binding.
      Replacement of the same residue with Tyr abolishes cooperativity while retaining
      sensitivity to allosteric inhibition and activation. Thus, this mutant has
      uncoupled homotropic from heterotropic allostery. Mutation of Asp103 to Ala
      results in an enzyme which retains wild-type Fru6P-binding characteristics with
      reduced activity. GDP, which allosterically activates the wild-type enzyme, acts
      as a mixed inhibitor for this mutant. Mutation of Thr125 to Ala and Asp129 to Ser
      produces mutants with impaired Fru6P binding and decreased cooperativity. In the
      presence of the activator GDP, both these mutants display apparent negative
      cooperativity. In addition, ATP binding is now allosterically altered by GDP.
      These results extend the number of active site residues known to participate in
      the catalytic process and help to define the mechanisms behind catalysis and
      homotropic and heterotropic allostery.

PMID- 1390711
TI  - Effect of doxorubicin on the order of the acyl chains of anionic and zwitterionic
      phospholipids in liquid-crystalline mixed model membranes: absence of drug
      induced segregation of lipids into extended domains.
AB  - We investigated the effect of the antineoplastic drug doxorubicin on the order of
      the acyl chains in liquid-crystalline mixed bilayers consisting of
      dioleoylphosphatidylserine (DOPS) or -phosphatidic acid (DOPA), and
      dioleoylphosphatidylcholine (DOPC) or -phosphatidylethanolamine (DOPE). Previous
      2H-NMR studies on bilayers consisting of a single species of di[11,11-2H2]oleoyl
      labeled phospholipid showed that doxorubicin does not affect the acyl chain order
      of pure zwitterionic phospholipid but dramatically decreases the order of anionic
      phospholipid [de Wolf, F. A., et al. (1991) Biochim. Biophys. Acta 1096, 67-80].
      In the present work, we studied mixed bilayers in which alternatively the anionic
      or the zwitterionic phospholipid component was 2H-labeled so as to monitor its
      individual acyl chain order. Doxorubicin decreased the order parameter of the
      mixed anionic and zwitterionic lipids by approximately the same amount and did
      not induce a clear segregation of the lipid components into extended, separate
      domains. The drug had a comparable disordering effect on mixed bilayers of
      unlabeled cardiolipin and 2H-labeled zwitterionic phospholipid, indicating the
      absence of extensive segregation also in that case. Upon addition of doxorubicin
      to bilayers consisting of 67 mol% DOPE and 33 mol% anionic phospholipid, a
      significant part of the lipid adopted the inverted hexagonal (HII) phase at 25
      degrees C. This bilayer destabilization, which occurred only in mixtures of
      anionic phospholipid and sufficient amounts of DOPE, might be of physiological
      importance. Even upon formation of extended HII-phase domains, lipid segregation
      was not clearly detectable, since the relative distribution of 2H-labeled anionic
      phospholipid and [2H]DOPE between the bilayer phase and HII phase was very
      similar. Our findings argue against a role of extensive anionic/zwitterionic
      lipid segregation in the mechanism of action and toxicity of doxorubicin.

PMID- 1390712
TI  - Band-3 mediated uptake of beryllofluoride complexes by human erythrocytes.
AB  - Beryllium forms several multivalent fluoride complexes in aqueous solution; the
      relative concentration of each is governed by the relative concentrations of the
      constituent ions and pH. In 9Be NMR spectra the 9Be (spin = 3/2) and 19F (spin =
      1/2) spin coupling gave rise to an overlapping resonance triplet, quartet, and
      quintet of BeF2, BeF3-, and BeF4(2-), respectively. The low frequency shift of
      the quartet (0.31 ppm) and the quintet (0.62 ppm) from the triplet correlated
      with an increase in the number of 19F-ions in each complex. 19F NMR spectra of
      the complexes showed that the spin-coupled quartet of each complex was
      progressively shifted to higher frequency with an increase in the number of F-
      ions in the complex. Using 9Be and 19F NMR, the multiple equilibrium mixture of
      complexes was found to shift substantially to favor the BeF3- and BeF4(2-) with a
      relative increase of NaF concentration. The association constants for BeF2, BeF3
      , and BeF4(2-) at 25 degrees C were determined directly from the peak intensities
      of the spectra, and by a numerical fitting procedure for multiple spectra, and
      were 0.51 +/- 0.17 mM-2, 0.26 +/- 0.03 mM-1, and 1.0 x 10(-2) +/- 0.1 x 10(-2) mM
      1, respectively. 19F NMR spectra of human erythrocytes to which Be2+ and F- were
      added showed separate resonances from the intracellular populations of the
      complexes and these were shifted to higher frequency from their extracellular
      counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390713
TI  - Kinetics and thermodynamics of triple-helix formation: effects of ionic strength
      and mismatches.
AB  - Thermodynamic and kinetic parameters for the triplex-forming reactions between a
      homopurine-homopyrimidine 22-base-pair duplex (sequence of the purine strand:
      5'd[AAAGGAGGAGAAGAAGAAAAAA]3') and the four 22-dN third strands (22 dN:
      5'd[TTTCCTCCTCTNCTTCTTTTTT]3', where N = A, C, T, or G) were determined from
      thermal denaturation and renaturation UV absorbance profiles. Cooling and heating
      curves were not superimposable and thus allowed us to determine the rate
      constants of association (k(on)) and dissociation (k(off)) as a function of
      temperature, assuming a two-state model analogous to that developed for duplex
      forming reactions. Experiments were performed in 10 mM cacodylate buffer (pH 6.8)
      in the presence of NaCl concentrations ranging from 20 to 300 mM. Within
      experimental accuracy, the main results are the following: (i) The rate constants
      k(on) and k(off) result in linear Arrhenius plots, consistent with the prediction
      of two-state association and dissociation (ii) k(on) is independent of the nature
      of the base N located in the center of the third strand. (iii) k(on) strongly
      decreases when the NaCl concentration is decreased. (iv) The activation energy,
      E(on), is always negative and becomes more negative when the NaCl concentration
      is decreased. (v) k(off) is independent of NaCl concentration but depends on the
      base N, with its magnitude following the order C greater than G greater than A
      much greater than T. (vi) The activation energy, E(off), is independent of the
      base N. All these results are discussed in the light of a nucleation-zipping
      model similar to that developed for the duplex-coil transitions [Craig, M. E.,
      Crothers, D. M., & Doty, P. (1971) J. Mol. Biol. 62, 383-401; Porschke, D.,
      Eigen, M. (1971) J. Mol. Biol. 62, 361-381].

PMID- 1390714
TI  - Structural organization and stability of a thermoresistant domain generated by in
      vivo hydrolysis of the alpha-crystallin B chain from calf lens.
AB  - A protein fragment (M(r) approximately 9000) isolated from the cortex of
      nonpathological calf lenses has been structurally characterized. The polypeptide
      structure was well organized (39% alpha-helix, 33% beta-structure, and 28%
      remainder) according to the far-ultraviolet circular dichroism. The fluorescence
      was heterogeneous for the presence of two tryptophan classes. Structure
      perturbation by pH and denaturant revealed cooperative structural transitions
      which are characteristics of a globular organization. A single-step unfolding
      curve induced by Gdn-HCl (midpoint = 1.38 M Gdn-HCl) was monitored by emission
      maximum shift as well as by far-ultraviolet circular dichroism. This transition
      was analyzed as a two-state process. The standard free energy of unfolding in the
      absence of the denaturant, delta Go (H2O), was found to be 10.80 +/- 0.25 kJ/mol
      at 20 degrees C and pH 7.4. The fragment also shows an unusual thermal
      resistance. Its structure was unperturbed up to 90 degrees C according to the
      fluorescence and dichroism. This last property, its peculiar amino acid
      composition, and the sequence of a small segment are shared, among crystallins,
      only with the N-terminal region of the alpha-crystallin B chain. A search for
      proteolysis sites along the alpha-crystallin B chain sequence revealed that it
      possesses specific points for proteinase attack. These sites are particularly
      exposed and clustered in a very flexible region in the middle of the protein
      sequence. They are also well represented in the C-terminal extension of the
      molecule while a few are buried in the N-terminal region.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1390715
TI  - Structural and functional characterization of the mutant Escherichia coli
      glutaredoxin (C14----S) and its mixed disulfide with glutathione.
AB  - Glutaredoxin is essential for the glutathione (GSH)-dependent synthesis of
      deoxyribonucleotides by ribonucleotide reductase, and in addition, it displays a
      general GSH disulfide oxidoreductase activity. In Escherichia coli glutaredoxin,
      the active site contains a redox-active disulfide/dithiol of the sequence Cys11
      Pro12-Tyr13-Cys14. In this paper, we have prepared and characterized the Cys14---
      Ser mutant of E. coli glutaredoxin and its mixed disulfide with glutathione. The
      Cys14----Ser mutant of glutaredoxin is shown to retain 38% of the GSH disulfide
      oxidoreductase activity of the wild-type protein with hydroxyethyl disulfide as
      substrate but to be completely inactive with ribonucleotide reductase,
      demonstrating that dithiol glutaredoxin is the hydrogen donor for ribonucleotide
      reductase. The covalent structure of the mixed disulfide of glutaredoxin(C14S)
      with GSH prepared with 15N-labeling of the protein was confirmed with nuclear
      magnetic resonance (NMR) spectroscopy, establishing a basis for NMR structural
      studies of the glutathione binding site on glutaredoxin.

PMID- 1390716
TI  - Equilibrium denaturation of recombinant porcine growth hormone.
AB  - Equilibrium denaturation of recombinant porcine growth hormone (pGH) derived from
      Escherichia coli using the denaturant guanidine hydrochloride (GuHCl) was
      followed by ultraviolet absorption spectroscopy, intrinsic fluorescence, far
      ultraviolet circular dichroism, and size-exclusion chromatography. The normalized
      denaturation transition curves for each of the above methods were not coincident;
      denaturation resulted in an initial disruption of the tertiary structure, whereas
      secondary structure and degree of compactness were disrupted at higher
      concentrations of denaturant. Size-exclusion chromatography also detected an
      associated form of pGH at intermediate GuHCl concentrations. These findings
      conclusively show that pGH does not follow a simple two-state folding mechanism
      but are consistent with the framework model of folding. Stable intermediates
      observed were similar to those seen in other nonhuman growth hormones and are
      characterized as compact and largely alpha-helical yet lacking nativelike
      tertiary structure.

PMID- 1390717
TI  - Quantitative footprinting analysis of the chromomycin A3--DNA interaction.
AB  - Chromomycin A3 (CHR) binding to the duplex
      d(CAAGTCTGGCCATCAGTC).d(GACTGATGGCCAGACTTG) has been studied using quantitative
      footprinting methods. Previous NMR studies indicated CHR binds as a dimer in the
      minor groove. Analysis of autoradiographic spot intensities derived from DNase I
      cleavage of the 18-mer in the presence of various amounts of CHR revealed that
      the drug binds as a dimer to the sequence 5'-TGGCCA-3',3'-ACCGGT-5' in the 18-mer
      with a binding constant of (2.7 +/- 1.4) x 10(7) M-1. Footprinting and
      fluorescence data indicate that the dimerization constant for the drug in
      solution is approximately 10(5) M-1. Since it has been suggested that CHR binding
      alters DNA to the A configuration, quantitative footprinting studies using
      dimethyl sulfate, which alkylates at N-7 of guanine in the major groove, were
      also carried out. Apparently, any drug-induced alteration in DNA structure does
      not affect cleavage by DMS enough to be observed by these experiments.

PMID- 1390719
TI  - Conformation of beta-methylmelibiose bound to the ricin B-chain as determined
      from transferred nuclear Overhauser effects.
AB  - Transferred nuclear Overhauser effect (TRNOE) experiments have revealed a change
      in the torsion angles about the alpha-1-6 glycosidic bond of methyl beta
      melibioside upon binding of the melibioside to the ricin B-chain (Rb). A full
      relaxation rate matrix simulation of experimental buildup curves aided in
      quantitative interpretation of 1D selective inversion recovery TRNOE experiments.
      The data are consistent with a model in which both major (omega approximately 170
      degrees) and minor (omega approximately -60 degrees) conformers for methyl beta
      melibioside are significantly populated in solution while the Rb/methyl beta
      melibioside complex has little of the minor conformer populated. The results
      indicate that the ricin B-chain excludes binding of certain ligand conformations
      on the basis of unfavorable interactions between the protein surface and remote
      portions of the disaccharide system.

PMID- 1390718
TI  - Neither delta- nor lambda-tris(phenanthroline)ruthenium(II) binds to DNA by
      classical intercalation.
AB  - Equilibrium binding studies and viscosity experiments are described that
      characterize the interaction of delta- and lambda-[Ru(o-phen)3]2+ with calf
      thymus DNA. The mode of binding of these compounds to DNA is a matter of
      controversy. Both isomers of [Ru(o-phen)3]2+ were found to bind but weakly to
      DNA, with binding constants of 4.9 (+/- 0.3) x 10(4) M-1 and 2.8 (+/- 0.2) x
      10(4) M-1 determined for the delta and lambda isomers, respectively, at 20
      degrees C in a solution containing 5 mM Tris-HCl (pH 7.1) and 10 mM NaCl. We
      determined that the quantity delta log K/delta log [Na+] equals 1.37 and 1.24 for
      the delta and lambda isomers, respectively. Application of polyelectrolyte theory
      allows us to use these values to show quantitatively that both the delta and
      lambda isomers are essentially electrostatically bound to DNA. Viscosity
      experiments show that binding the lambda isomer does not alter the relative
      viscosity of DNA to any appreciable extent, while binding of the delta isomer
      decreases the relative viscosity of DNA. From these viscosity results, we
      conclude that neither isomer of [Ru(o-phen)3]2+ binds to DNA by classical
      intercalation.

PMID- 1390720
TI  - Crystal structure and ligand-binding studies of a screened peptide complexed with
      streptavidin.
AB  - The thermodynamic binding parameters and crystal structure for streptavidin
      peptide complexes where the peptide sequences were obtained by random screening
      methods are reported. The affinities between streptavidin and two heptapeptides
      were determined by titrating calorimetric methods [Phe-Ser-His-Pro-Gln-Asn-Thr,
      Ka = 7944 (+/- 224) M-1, delta G degrees = -5.32 (+/- 0.01) kcal/mol, and delta H
      degrees = -19.34 (+/- 0.48) kcal/mol; His-Asp-His-Pro-Gln-Asn-Leu, Ka = 3542 (+/-
      146) M-1, delta G degrees = -4.84 (+/- 0.03) kcal/mol, and delta H degrees = 
      19.00 (+/- 0.64) kcal/mol]. The crystal structure of streptavidin complexed with
      one of these peptides has been determined at 2.0-A resolution. The peptide (Phe
      Ser-His-Pro-Gln-Asn-Thr) binds in a turn conformation with the histidine,
      proline, and glutamine side chains oriented inward at the biotin-binding site. A
      water molecule is immobilized between the histidine and glutamine side chains of
      the peptide and an aspartic acid side chain of the protein. Although some of the
      residues that participate in binding biotin also interact with the screened
      peptide, the peptide adopts an alternate method of utilizing binding determinants
      in the biotin-binding site of streptavidin.

PMID- 1390721
TI  - Deuterium NMR relaxation studies of peptide-lipid interactions.
AB  - A unique model membrane system composed of a synthetic amphiphilic peptide (Lys2
      Gly-Leu16-Lys2-Ala-amide) and a specifically labeled phospholipid (1,2-[7,7
      2H2]dipalmitoyl-sn-glycero-3-phosphocholine) has been studied by 2H NMR, using
      inversion recovery, quadrupolar echo, and modified Jeener-Broekaert sequences,
      from 213 to 333 K, at molar peptide concentrations of 0, 2, 4, and 6%. Analysis
      of the experiments, employing a density matrix treatment based on the stochastic
      Liouville equation, revealed information about the dynamic organization of the
      lipid in the model membrane system, whose phase behavior has been determined
      previously [Huschilt et al. (1985) Biochemistry 24, 1377-1386]. The dynamic
      organization is described in terms of segmental and molecular order parameters
      and in terms of correlation times corresponding to both internal and overall
      lipid motions. In the liquid crystalline phase, the molecular order parameter,
      SZZ, was observed to decrease slightly upon addition of peptide while the
      conformational order parameter corresponding to the seventh segment, SZ'Z', did
      not change for any concentration of peptide. In general, the gauche-trans
      isomerization rate in the middle of the chain was not observed to change upon
      peptide addition, whereas the whole body reorientational correlation times (tau R
      parallel and tau R perpendicular) increased by nearly an order of magnitude. The
      anisotropy ratio (tau R perpendicular/tau R parallel) decreased with peptide
      added. An additional motion which involves a jump about the axis of the sn-2
      chain is also observed to be slowed down significantly in the presence of
      peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390722
TI  - Why water-soluble, compact, globular proteins have similar specific enthalpies of
      unfolding at 110 degrees C.
AB  - The changes in free energy, enthalpy, and entropy of unfolding have been measured
      for many water-soluble, compact, globular proteins by a number of workers. In
      principle, a wide range in stability could be achieved by proteins, as measured
      by the free energy of unfolding; in practice, evolution only allows a narrow
      range in this quantity. Proteins are only marginally stable at room temperature
      for many possible reasons, including ensuring that folding is reversible and
      polypeptide chains are not trapped in incorrectly folded structures. Many of
      these proteins have approximately the same values of enthalpy of unfolding around
      110 degrees C. We show here that this arises because the change in entropy of
      unfolding at room temperature and the change in heat capacity on unfolding, which
      governs the temperature variation of the enthalpy and entropy, both vary with the
      magnitude of the hydrophobic effect in the protein. As all these proteins have
      evolved to achieve similar stabilities at room temperature, the enthalpy of
      unfolding will also vary with the size of the hydrophobic effect in the protein.
      A consequence of this is that curves of the specific unfolding enthalpy against
      temperature for different proteins intersect around 110 degrees C. A similar
      conclusion, on the basis of similar melting points rather than similar free
      energies of unfolding, has been reached independently by Baldwin and Muller (R.
      L. Baldwin, personal communication).

PMID- 1390723
TI  - Sequence-specific oxidative cleavage of DNA by a designed metalloprotein,
      Ni(II).GGH(Hin139-190).
AB  - A 55-residue protein containing the DNA binding domain of Hin recombinase,
      residues 139-190, with the tripeptide Gly-Gly-His (GGH) at the NH2 terminus was
      synthesized by stepwise solid-phase methods. GGH(Hin139-190) binds sequence
      specifically to DNA at four 13 base pair sites (termed hixL and secondary) and,
      in the presence of Ni(OAc)2 and monoperoxyphthalic acid, reacts predominantly at
      a single deoxyribose position on one strand of each binding site [Mack, D.P., &
      Dervan, P.B. (1990) J. Am. Chem. Soc. 112, 4604]. We find that, upon treatment
      with n-butylamine, the DNA termini at the cleavage site are 3'- and 5'-phosphate,
      consistent with oxidative degradation of the deoxyribose backbone. The nickel
      mediated oxidation can be activated with peracid, iodosylbenzene, or hydrogen
      peroxide. The sequence specificity of the reaction is not dependent on oxidant,
      but the rates of cleavage differ, decreasing in the order peracid greater than
      iodosylbenzene greater than hydrogen peroxide. Optimal cleavage conditions for a
      1 microM concentration of protein are 50 microM peracid, pH 8.0, and 1 equiv of
      Ni(OAc)2. The preferential cleavage at a single base pair position on one strand
      of the minor groove indicates a nondiffusible oxidizing species. A change of
      absolute configuration in the GGH metal binding domain from L-His to D-His
      [Ni(II).GG-(-D-)H(Hin139-190)] affords cleavage at similar base pair locations
      but opposite with regard to strand specificity.

PMID- 1390724
TI  - N-terminal domain of Avena phytochrome: interactions with sodium dodecyl sulfate
      micelles and N-terminal chain truncated phytochrome.
AB  - Phytochrome is the ubiquitous red light photoreceptor present in plants.
      Properties of the 6-kDa end terminal region of phytochrome A (PHYA from etiolated
      Avena) have been investigated by the use of synthetic polypeptide fragments
      corresponding to that region. This region of the phytochrome A protein has been
      viewed as a possible functional site due to the large differences in the
      sequence's conformation and exposure between the Pr (red light-absorbing form)
      and Pfr (far-red light-absorbing, gene-regulating form) species of phytochrome A.
      Hydrophobic moment calculations reveal amphiphilic helical potential in this
      section of the protein, consistent with the folding of the N-terminal region onto
      a hydrophobic chromophore/chromophore pocket. A large N-terminal synthetic
      peptide also demonstrated helical folding in the presence of SDS micelles. This
      experimental evidence indicates that the N-terminal alpha-helical folding upon
      conversion of the regulatorily inactive Pr to the active Pfr form of phytochrome
      A is likely driven at least in part by amphiphilic helix stabilization. Further,
      the large synthetic peptide was spectrally demonstrated to interact with
      phytochrome A lacking the N-terminal region. The formation of this nativelike
      complex may provide us with a tool for both biophysical and physiological studies
      on the mechanism of phytochrome A signal transduction.

PMID- 1390726
TI  - Isolation of a carboxyphosphate intermediate and the locus of acetyl-CoA action
      in the pyruvate carboxylase reaction.
AB  - When chicken liver pyruvate carboxylase was incubated with either H14CO3- or
      gamma-[32P]ATP, a labeled carboxyphospho-enzyme intermediate could be isolated.
      The complex was catalytically competent, as determined by its subsequent ability
      to transfer either 14CO2 to pyruvate or 32P to ADP. While the carboxyphospho
      enzyme complex was inherently unstable and the stoichiometry of the transfer was
      variable depending on experimental conditions, both the [14C]carboxyphospho
      enzyme and the carboxy[32P]phospho-enzyme had similar half-lives. Acetyl-CoA was
      shown to be involved in the conversion of the carboxyphospho-enzyme complex to
      the more stable carboxybiotin-enzyme species, which was consistent with the
      effects of acetyl-CoA on isotope exchange reactions involving ATP. We were unable
      to detect the formation of a phosphorylated biotin derivative during the ATP
      cleavage reaction. In the presence of K+ and at pH 9.5, the acetyl-CoA
      independent activity of chicken liver pyruvate carboxylase approached 2% of the
      acetyl-CoA-stimulated rate, which represents a 30-fold increase on previously
      reported activity for this enzyme.

PMID- 1390725
TI  - N-bromoacetyl-peptide substrate affinity labeling of vitamin K dependent
      carboxylase.
AB  - Vitamin K dependent carboxylase (carboxylase) is a membrane-associated
      endoplasmic reticular enzyme that catalyzes the conversion of certain glutamate
      residues of essential blood coagulation proteins to gamma-carboxyglutamyl (Gla)
      residues. A series of N-bromoacetyl-peptide substrate affinity labels based on
      the Gla domain of these blood-clotting proteins was synthesized, and the
      substrate and inactivator kinetic parameters were assessed. The most promising of
      these affinity peptides, N-bromoacetyl-FLEELY, was both substrate for carboxylase
      and an irreversible time-dependent inactivator of the enzyme, inactivating 80% of
      carboxylase under pseudo-first-order conditions. Addition of saturating amounts
      of a competing peptide substrate completely abolished the inhibitory properties
      of N-bromoacetyl-FLEELY, consistent with inactivation occurring at the active
      site. The partition ratio of inactivation/carboxylation was 1/30. The 94-kDa
      carboxylase was purified to 15-50% purity by a modification of a recent protocol
      [Wu, S.-M., Morris, D. P., & Stafford, D. W. (1991) Proc. Natl. Acad. Sci. U.S.A.
      88, 2236-2240] and covalently labeled with N-bromoacetyl-FLEEL[125I]Y. On silver
      stained 10% sodium dodecyl sulfate-polyacrylamide gels, the predominant
      radiolabeled band was the 94,000 molecular weight species. This result
      independently validates that the 94-kDa protein is a carboxylase.

PMID- 1390727
TI  - Mechanism of enantioselective oxygenation of sulfides catalyzed by
      chloroperoxidase and horseradish peroxidase. Spectral studies and
      characterization of enzyme-substrate complexes.
AB  - The binding of a series of alkyl aryl sulfides to chloroperoxidase (CPO) and
      horseradish peroxidase (HRP) has been investigated by optical difference
      spectroscopy, circular dichroism, paramagnetic NMR spectroscopy, and NMR
      relaxation measurements. The data are consistent with binding of the sulfides in
      the distal side of the heme pocket with CPO and near the heme edge with HRP. A
      linear correlation between the binding constants of para-substituted sulfides to
      CPO and the Taft sigma I parameter suggests that these substrates act as donors
      in donor-acceptor complexes involving some residue of the protein chain. Spectral
      studies during turnover show that high enantioselectivity in the CPO-catalyzed
      oxidation of sulfides results from a reaction pathway that does not involve the
      accumulation of compound II enzyme intermediate.

PMID- 1390728
TI  - Application of phosphate-backbone-modified oligonucleotides in the studies on
      EcoRI endonuclease mechanism of action.
AB  - Chemical synthesis of oligodeoxyribonucleotides modified at a preselected
      internucleotide bond by the replacement of one of the two "nonbridging" oxygens
      by a sulfur atom or an ethoxy group yields model substrates for studies on DNA
      protein interactions. Chromatographic (RP-HPLC) separation of the diastereomers
      of oligonucleotides containing EcoRI canonical sequence together with the
      assignment of the substituent orientation in the DNA molecule allowed study of
      the stereochemical aspects of DNA-EcoRI endonuclease interactions. The DNA
      segment involved in interactions between EcoRI protein and phosphate groups
      appeared to be larger than its canonical sequence, ...GAATTC..., and was extended
      to the nonamer. The modification of certain internucleotide bonds within this
      nonamer caused significant or complete protection against the nucleolytic action
      of EcoRI and, in some cases, manifested the diastereoselectivity of the enzyme.
      On the basis of the results of EcoRI-catalyzed hydrolysis of stereodefined
      phosphorothioate and phosphotriester substrates, we propose a model to explain
      this phenomenon at the molecular level.

PMID- 1390729
TI  - Nature of alcohol and anesthetic action on cooperative membrane equilibria.
AB  - A generalized, colligative thermodynamic framework is used to treat the action of
      solutes on cooperative membrane equilibria. Configurational entropy, the
      randomness imparted by solutes through the partitioning or mixing process, is
      implicated as the energetic driving force for the action of anesthetics on
      cooperative membrane equilibria. The equilibria predicted to be most sensitive to
      solute action--in which the dilute solute causes a perturbation equivalent to a
      large change in temperature--are (1) low-enthalpy processes that coincide with
      (2) large partitioning differences between states. The model stresses that
      solutes do not act at a single site, but on both states in an equilibrium, and
      that the perturbation is determined by the difference in entropy. Evidence for
      the thermodynamic framework is obtained from the partitioning behavior of the
      general anesthetic 1-hexanol into a model lecithin (DMPC; 1,2-dimyristoyl-sn
      glycero-3-phosphocholine) membrane as a function of temperature and alcohol
      concentration. The low-enthalpy equilibrium between the gel (L beta') and ripple
      states (P beta') (pretransition) is more sensitive to 1-hexanol than the high
      enthalpy equilibrium between the ripple (P beta') and fluid bilayer states (L
      alpha) (main transition). The perturbations of both equilibria are accurately
      described by the colligative thermodynamic framework. The results suggest that
      alcohols and anesthetics act through entropy to upset the natural thermal balance
      that maintains native membrane architecture.

PMID- 1390730
TI  - Probing the interactions of alcohols with biological membranes with the
      fluorescent probe Prodan.
AB  - Prodan [6-propionyl-2-(dimethylamine)naphthalene] is a hydrophobic fluorescent
      probe which is extremely sensitive to both the polarity and the hydrogen-bond
      donating capacity of the solvent. In binary mixtures of solvents, the hydrogen
      bond donating effect on Prodan fluorescence saturates at relatively low
      concentrations of protic solvent while the polarity effect is proportional to the
      mixture's dielectric constant. The fluorescence emission maximum is approximately
      a linear function of the dielectric constant in both protic and aprotic solvents,
      and this allows estimation of the dielectric constant in both environments. In
      phospholipid bilayers and biological membranes, Prodan exhibits two distinct
      emission peaks: blue (430-445 nm) and green (470-505 nm). Temperature determines
      the relative intensity of the two peaks, but their wavelengths depend on the type
      of membrane and appear to reflect a specific membrane environment. In
      phospholipid vesicles, alcohols reduce the fluorescence intensity of the blue
      peak and produce a red-shift in the emission maximum of the green peak. Taking
      the partition coefficients of the alcohols into account, short-chain alcohols are
      much more effective than longer-chain alcohols in red-shifting the emission
      maximum of the green peak. Alcohols have similar effects on Prodan fluorescence
      in liver microsomal and mitochondrial membranes, synaptosomal membranes, and red
      blood cell plasma membranes. However, in liver organelle membranes the red-shift
      of the green peak is the dominant effect while in plasma membranes the quenching
      of the fluorescence of the blue peak is dominant. These effects are observed at
      low (pharmacological) ethanol concentrations and provide a unique tool for
      probing the interactions of ethanol with biological membranes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1390731
TI  - Interaction of D-amino acid incorporated analogues of pardaxin with membranes.
AB  - The influence of specific L- to D-amino acid substitutions on the interaction of
      pardaxin, a shark repellent neurotoxin polypeptide, with phospholipid vesicles
      and human erythrocytes is described. Twelve modified, truncated, or fluorescently
      labeled [with the fluorophore 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD) at their N
      terminal amino acid] analogues of pardaxin were synthesized by a solid-phase
      method. Fluorescence measurements were used to monitor the interaction of the
      analogues with membranes [Rapaport, D., & Shai, Y. (1991) J. Biol. Chem. 266,
      23769-23775]. Upon titration of solutions containing the NBD-labeled peptides
      with small unilamellar vesicles, the fluorescent emission spectra of all NBD
      labeled peptides displayed similar blue-shifts, in addition to enhanced
      intensities, upon relocation of the probe to the more apolar environment. Binding
      isotherms were constructed from which surface partition constants, in the range
      of 10(4) M-1, were derived. The existence of an aggregation process, suggested by
      the shape of the binding isotherms, could be associated only with those analogues
      in which the N-helix (residues 1-9) was not perturbed. The alpha-helical content
      of the analogues was estimated by circular dichroism (CD) spectroscopy, both
      before and after binding to vesicles at neutral pH. The ability of the peptides
      to dissipate a diffusion potential and to cause calcein release, as well as to
      lyse human erythrocytes, served to functionally characterize the peptides. The
      results support a two alpha-helix model, with a bend at position 13, as best
      describing pardaxin in its membrane-bound state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390732
TI  - Use of protein unfolding studies to determine the conformational and dimeric
      stabilities of HIV-1 and SIV proteases.
AB  - The free energies of dimer dissociation of the retroviral proteases (PRs) of
      human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus
      (SIV) were determined by measuring the effects of denaturants on the protein
      fluorescence upon the unfolding of the enzymes. HIV-1 PR was more stable to
      denaturation by chaotropes and extremes of pH and temperature than SIV PR,
      indicating that the former enzyme has greater conformational stability. The urea
      unfolding curves of both proteases were sigmoidal and single phase. The midpoints
      of the transition curves increased with increasing protein concentrations. These
      data were best described by and fitted to a two-state model in which folded
      dimers were in equilibrium with unfolded monomers. This denaturation model
      conforms to cases in which protein unfolding and dimer dissociation are
      concomitant processes in which folded monomers do not exist [Bowie, J. U., &
      Sauer, R. T. (1989) Biochemistry 28, 7140-7143]. Accordingly, the free energies
      of unfolding reflect the stabilities of the protease dimers, which for HIV-1 PR
      and SIV PR were, respectively, delta GuH2O = 14 +/- 1 kcal/mol (Ku = 39 pM) and
      13 +/- 1 kcal/mol (Ku = 180 pM). The binding of a tight-binding, competitive
      inhibitor greatly stabilized HIV-1 PR toward urea-induced unfolding (delta GuH2O
      = 19.3 +/- 0.7 kcal/mol, Ku = 7.0 fM). There were also profound effects caused by
      adverse pH on the protein conformation for both HIV-1 PR and SIV PR, resulting in
      unfolding at pH values above and below the respective optimal ranges of 4.0-8.0
      and 4.0-7.0

PMID- 1390733
TI  - In vitro transcription analysis of DNA adducts induced by
      cyanomorpholinoadriamycin.
AB  - The reaction of cyanomorpholinoadriamycin (CMA) with DNA results in the formation
      of sequence-specific complexes with DNA. These complexes were revealed as blocked
      transcripts in an in vitro transcription assay--of 14 high-intensity blockages
      detected in the 120 bp probed in this assay, 12 were prior to GpG or CpC
      sequences. Slow read-through past the first few sites exhibited first-order
      kinetics, with half-lives of 25-200 min. Bidirectional transcription footprinting
      revealed nine high-intensity sites, eight of which were defined by a GpG element
      (nontemplate strand). Reaction of CMA with single-strand DNA, followed by a
      primer-extension assay, revealed four major blockages all of which were at GpG
      sites on the initial single-strand DNA. From a combination of these three
      experimental approaches, it appears that CMA yields dominantly intrastrand cross
      links between adjacent guanine residues. Since CMA is also known to form
      interstrand cross-links, these appear to occur at GpC sequences but are minor in
      comparison to the extent of formation of intrastrand cross-links.

PMID- 1390734
TI  - Acetylation of prostaglandin endoperoxide synthase by N-acetylimidazole:
      comparison to acetylation by aspirin.
AB  - Treatment of prostaglandin endoperoxide (PGH) synthase apoprotein with a 100- or
      1000-fold excess of N-acetylimidazole (NAI) led to time-dependent inactivation of
      both cyclooxygenase and peroxide activities. Reconstitution of apoprotein with
      heme prior to incubation with NAI substantially protected the enzyme from
      inactivation. Pretreatment of the protein with either acetylsalicylic acid
      (aspirin) or (+/-)-2-fluoro-alpha-methyl-4-biphenylacetic acid (flurbiprofen),
      which inhibit cyclooxygenase activity, did not alter the time course of
      peroxidase inactivation by NAI. Treatment of NAI-inactivated apoPGH synthase with
      hydroxylamine led to substantial regeneration of both cyclooxygenase and
      peroxidase activities. Quantitation of radioactivity following incubation of PGH
      synthase with [3H-acetyl]NAI indicated incorporation of 1.7 +/- 0.9 acetyl
      groups/70-kDa subunit. Cleavage of acetylated protein with trypsin under
      nondenaturing conditions followed by high-performance liquid chromatography
      analysis demonstrated that most of the radioactivity was incorporated into the 33
      kDa fragment although significant radioactivity was also detectable in the 38-kDa
      fragment. Chymotryptic peptide mapping of acetylated protein revealed numerous
      potential sites of acetylation distributed in widely divergent regions of the
      protein. No apparent differences were observed between the chymotryptic maps of
      apo- and holoenzyme, suggesting that the adduct responsible for loss of catalytic
      activity is unstable to the chromatographic conditions. The different biochemical
      properties of PGH synthase acetylated by NAI or aspirin suggest that a major
      determinant of the specificity of aspirin for Ser530 is binding of the salicylate
      moiety to this region of the PGH synthase protein.

PMID- 1390735
TI  - The C-terminal domain of Escherichia coli ribosomal protein L7/L12 can occupy a
      location near the factor-binding domain of the 50S subunit as shown by cross
      linking with N-[4-(p-azidosalicylamido)butyl]-3-(2'-pyridyldithio)propionamide.
AB  - All large ribosomal subunits contain two dimers composed of small acidic proteins
      that are involved in binding elongation factors during protein synthesis. The
      ribosomal location of the C-terminal globular domain of the Escherichia coli
      ribosomal acidic protein L7/L12 has been determined by protein cross-linking with
      a new heterobifunctional, reversible, photoactivatable reagent, N-[4-(p
      azidosalicylamido)-butyl]-3-(2'-pyridyldithio)propionamide . Properties of this
      reagent are described. It was first radiolabeled with 125I and then attached
      through the formation of a disulfide bond to a unique cysteine of L7/L12,
      introduced by site-directed mutagenesis at residue 89. Intact 50S ribosomal
      subunits were reconstituted from L7/L12-depleted cores and the radiolabeled
      L7/L12Cys89. Irradiation of the reconstituted subunits resulted in photo-cross
      linking between residue 89 and other ribosomal components. Reductive cleavage of
      the disulfide cross-link resulted in transfer of the 125I label from L7/L12Cys89
      to the other cross-linked components. Two radiolabeled proteins were identified,
      L11 and L10. The location of both of these proteins is well established to be at
      the base of the L7/L12 stalk near the binding sites for the N-terminal domain of
      both L7/L12 dimers, and for elongation factors. The result indicates that L7/L12
      can have a bent conformation bringing the C-terminal domain of at least one of
      the L7/L12 dimers at or near the factor-binding domain. The cross-linking method
      with radiolabeled N-[4-(p-azidosalicylamido)butyl]-3-(2'
      pyridyldithio)propionamide should be applicable for studies of other
      multicomponent complexes that can be reconstituted.

PMID- 1390737
TI  - Multidomain binding of transforming growth factor alpha to the epidermal growth
      factor receptor.
AB  - Solubilized epidermal growth factor receptor (EGF-R) has been used in an
      extension of the Geysen epitope mapping protocol in order to provide additional
      insight into the amino acid residues in human transforming growth factor alpha
      (hTGF alpha) which are critical to recognition and binding. Overlapping
      heptapeptides which encompassed the 50 amino acid primary sequence of hTGF alpha
      were synthesized on a polyethylene solid phase, and the amount of detergent
      solubilized EGF-R bound to each peptide was measured using ELISA. EGF-R appeared
      to bind reproducibly to four heptapeptides cognate to sequences in both the N-
      and C-domains of hTGF alpha (residues 22-28, 28-34, 36-42, and 44-50).
      Visualization of these four regions on three-dimensional solution phase
      structures of hTGF alpha, derived from 1H NMR measurements [Kline, T.-P., Brown,
      F.K., Brown, S.C., Jeffs, P.W., Kopple, K.D., & Mueller, L. (1990) Biochemistry
      29, 7805-7813], indicated that the peptide segments are located on a single face
      of the protein and suggested the presence of a potential receptor binding cavity.
      If peptide segments within both the N- and C-domains of hTGF alpha are involved
      in binding to EGF-R, then this has direct consequences for possible molecular
      mechanisms by which receptor activation might take place. For example, the
      observed conformational flexibility in the six NMR-derived hTGF alpha structures
      due to variations in the main-chain torsion angles of Val-33, in combination with
      the involvement of residues from both domains in the proposed binding cavity, may
      imply that receptor activation results from interdomain reorientation in the
      protein ligand.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390736
TI  - Genomic cloning of the gene for an IgE-binding lectin reveals unusual utilization
      of 5' untranslated regions.
AB  - epsilon BP (for epsilon binding protein) is a M(r) 31,000 S-type animal lectin
      that binds to IgE and has been identified as the homologue of Mac-2, a macrophage
      cell-surface marker, as well as the lectins RL-29, CBP35, and L-34. The protein
      is composed of two domains with the amino-terminal portion containing tandem
      repeats of nine amino acids and the carboxyl-terminal half containing consensus
      sequences shared by S-type animal lectins. We determined the genomic map in both
      rat and mouse and isolated overlapping genomic clones that contain the 5' two
      thirds of the murine gene. The remaining portion of the gene was obtained by
      polymerase chain reaction (PCR) amplification of genomic murine DNA followed by
      subcloning into plasmid vectors. The epsilon BP gene is composed of six exons
      separated by five introns. The entire amino-terminal repetitive sequence is
      contained in exon III, and the carboxyl-terminal domain is encoded by the three
      succeeding exons (IV, V, VI). The latter three exons correspond well in size and
      share sequence homology with three exons coding for 14-kDa S-type lectins. The
      sequence in exon I offers an explanation for the generation of two mRNAs
      differing only in their 5' untranslated sequences, previously reported in Mac-2
      cDNA clones. Using cDNA synthesis and PCR amplification, we determined that two
      alternative splice sites are used in many different types of cells. This
      alternative splicing results in different 5' untranslated regions of the murine
      epsilon BP mRNA.

PMID- 1390738
TI  - Determination of the solution structure of a synthetic two-site calcium-binding
      homodimeric protein domain by NMR spectroscopy.
AB  - The solution structure of a 34-residue synthetic calcium-binding peptide from
      site III of chicken troponin-C has been determined by 1H NMR spectroscopy. In
      solution and in the presence of calcium this peptide forms a symmetric two-site
      homodimeric calcium-binding domain (Shaw et al., 1990). The solution structure of
      this dimer was determined from the measurement of 470 NOEs from a 75-ms NOESY
      data set. For the dimer structure determination, the constraint list included 868
      distance restraints, 44 phi angles, and 24 chi 1 and 2 chi 2 angles. Seven
      structures were calculated by restrained molecular dynamics using a procedure in
      which intramonomer distances were used first and then all distances, intra- and
      intermonomer, were input during further dynamics. The structures exhibited a fold
      very similar to the C-terminal domain of troponin-C comprised of a pair of helix
      loop-helix calcium-binding sites. The rms deviation of these structures for
      backbone atoms between residues 97-122 and 97'-122' for the dimer was 0.82 A. The
      dimer structure was also calculated to be more symmetric than sites III and IV in
      troponin-C.

PMID- 1390739
TI  - Crystal and molecular structure of a DNA fragment containing a 2-aminoadenine
      modification: the relationship between conformation, packing, and hydration in Z
      DNA hexamers.
AB  - The crystal and molecular structure of d(CGUA'CG)2 (where A' is 2-aminoadenine)
      has been determined and refined to an R factor of 13.8% for data 8.0-1.3 A. The
      structure is very similar to the original Z-DNA structures with the sequence
      d(CGCGCG)2 [Gessner, R. V., Frederick, C. A., Quigley, G. J., Rich, A., & Wang,
      A. H.-J. (1989) J. Biol. Chem. 264, 7921] and shows that the substitution of 2
      aminoadenine-uracil base pairs in the two central steps is consistent with Z-DNA
      formation. In addition, we show how waters mediating intermolecular interactions
      may help to explain the ZI-ZII conformational pattern found in many Z-DNA
      structures.

PMID- 1390740
TI  - A sequence element necessary for self-cleavage of the antigenomic hepatitis delta
      RNA in 20 M formamide.
AB  - The genomic and antigenomic RNAs of hepatitis delta virus are capable of self
      cleavage and show no significant sequence similarities to other known self
      cleaving RNAs. We have derived an antigenomic delta RNA which cleaves to
      completion in 15 s in 9 mM magnesium at 37 degrees C and is capable of efficient
      self-cleavage in concentrations of formamide as high as 20 M. Cleavage in high
      concentrations of denaturant is dependent upon the presence of a polypurine
      sequence element, GGAGA, located between 81 and 85 nucleotides downstream of the
      cleavage site. Mutation of the initial G81G82 to C81C82, or removal of the
      sequence element, results in a loss of the ability to cleave in high formamide
      concentrations. Changing the final U-2C-1 of a pyrimidine-rich region, UCUUC,
      just upstream of the cleavage site, to G-2G-1 severely affects the self-cleavage,
      but introducing the two mutations, GG to CC and UC to GG, into the same molecule,
      restoring potential base pairing, partially restores the formamide stability.
      Relocating the GGAGA sequence upstream of the cleavage site also results in
      partial restoration of the formamide cleavage. Although the GGAGA sequence is
      important for self-cleavage under denaturing conditions, it does not appear to be
      necessary for HDV RNA cleavage in normal buffer conditions.

PMID- 1390741
TI  - 2'-Fluoro- and 2'-amino-2'-deoxynucleoside 5'-triphosphates as substrates for T7
      RNA polymerase.
AB  - 2'-Fluoro- and 2'-amino-2'-deoxynucleoside 5'-triphosphates have been
      investigated as substrates for T7 RNA polymerase. Michaelis-Menten kinetic
      parameters are reported for the incorporation of 2'-fluoro-2'-deoxyuridine, 2'
      fluoro-2'-deoxycytidine, and 2'-amino-2'-deoxyuridine into runoff transcripts.
      The 2'-amino derivative of uridine is a better substrate than the 2'-fluoro
      derivative. Gel electrophoretic analysis shows that full-length transcripts with
      a length of 2500 nucleotides can be obtained with the analogues, although a
      considerable amount of shorter fragments accompanies the full-length product. In
      keeping with the kinetic analysis, the 2'-aminouridine triphosphate gives a
      cleaner product than the 2'-fluoro analogue. Transcription of two tRNA genes
      shows that such shorter templates can be transcribed to full-length products
      essentially without premature termination with any of the analogues.

PMID- 1390742
TI  - Nonidentical DNA-binding sites of endonuclease NaeI recognize different families
      of sequences flanking the recognition site.
AB  - NaeI endonuclease uses a two-site binding mechanism to cleave substrate DNA:
      reaction-rate studies imply that occupancy of the second DNA site causes an
      allosteric change in the protein that enables DNA cleavage at the first site
      [Conrad, M., & Topal, M. D. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9707-9711].
      Measurements of relative binding affinities for 14-base-pair DNA fragments
      containing the NaeI recognition sequence GCCGGC and various flanking sequences
      showed that the two DNA-binding sites are not identical. G.C-rich flanking
      sequences were preferred by the activator binding site, whereas A.T-rich flanking
      sequences were preferred by the substrate binding site: GGGTGCCGGCAGGG was
      preferred 8-fold more by the activator site but 14-fold less by the substrate
      site than TTTCGCCGGCGTTT. Substitution of pyrimidine or 7-deazapurine for purine
      immediately 3' to GCCGGC reduced DNA affinity for only the activator site by up
      to 26-fold, implying that the activator DNA-binding site requires N-7 base
      contacts immediately flanking GCCGGC. The implications of nonidentical DNA
      binding sites, one of which binds a specific DNA site to allosterically activate
      the other, are discussed.

PMID- 1390743
TI  - Three-dimensional solution structure of the B domain of staphylococcal protein A:
      comparisons of the solution and crystal structures.
AB  - The three-dimensional solution structure of the recombinant B domain (FB) of
      staphylococcal protein A, which specifically binds to the Fc portion of
      immunoglobulin G, was determined by NMR spectroscopy and hybrid distance geometry
      dynamical simulated annealing calculations. On the basis of 692 experimental
      constraints including 587 distance constraints obtained from the nuclear
      Overhauser effect (NOE), 57 torsion angle (phi, chi 1) constraints, and 48
      constraints associated with 24 hydrogen bonds, a total of 10 converged structures
      of FB were obtained. The atomic root mean square difference among the 10
      converged structures is 0.52 +/- 0.10 A for the backbone atoms and 0.98 +/- 0.08
      A for all heavy atoms (excluding the N-terminal segment from Thr1 to Glu9 and the
      C-terminal segment from Gln56 to Ala60, which are partially disordered). FB is
      composed of a bundle of three alpha-helices, i.e., helix I (Gln10-His19), helix
      II (Glu25-Asp37), and helix III (Ser42-Ala55). Helix II and helix III are
      antiparallel to each other, whereas the long axis of helix I is tilted at an
      angle of about 30 degrees with respect to those of helix II and helix III. Most
      of the hydrophobic residues of FB are buried in the interior of the bundle of the
      three helices. It is suggested that the buried hydrophobic residues form a
      hydrophobic core, contributing to the stability of FB.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1390744
TI  - A possible role for the conserved trimer interface of ferritin in iron
      incorporation.
AB  - Ferritin is a large protein, highly conserved among higher eukaryotes, which
      reversibly stores iron as a mineral of hydrated ferric oxide. Twenty-four
      polypeptides assemble to form a hollow coat with the mineral inside. Multiple
      steps occur in iron core formation. First, Fe2+ enters the protein. Then, several
      alternate paths may be followed which include oxidation at site(s) on the
      protein, oxidation on the core surface, and mineralization. Sequence variations
      occur among ferritin subunits which are classified as H or L; Fe2+ oxidation at
      sites on the protein appears to be H-subunit-specific or protein-specific. Other
      steps of ferritin core formation are likely to involve conserved sites in
      ferritins. Since incorporation of Fe2+ into the protein must precede any of the
      other steps in core formation, it may involve sites conserved among the various
      ferritin proteins. In this study, accessibility of Fe2+ to 1,10-phenanthroline,
      previously shown to be inaccessible to Fe2+ inside ferritin, was used to measure
      Fe2+ incorporation in two different ferritins under various conditions. Horse
      spleen ferritin (L/H = 10-20:1) and sheep spleen ferritin (L/H = 1:1.6) were
      compared. The results showed that iron incorporation measured as inaccessibility
      of Fe2+ to 1,10-phenanthroline increased with pH. The effect was the same for
      both proteins, indicating that a step in iron core formation common among
      ferritins was being measured. Conserved sites previously proposed for different
      steps in ferritin core formation are at the interfaces of pairs and trios of
      subunits. Dinitrophenol cross-links, which modify pairs of subunits and affect
      iron oxidation, had no effect on Fe2+ incorporation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1390745
TI  - Kinetic resolution of peptide bond and side chain far-UV circular dichroism
      during the folding of hen egg white lysozyme.
AB  - The kinetics of regain of the native ellipticity in the far- and near-UV spectra
      have been investigated during the refolding at pH 7.8 and 20 degrees C of
      guanidine-unfolded, nonreduced hen egg white lysozyme. Stopped-flow studies
      showed that the ellipticities at 260 and 289.5 nm exhibit biphasic kinetics with
      rate constants of about 50 s-1 and 2.5 s-1 for the rapid and slow phase,
      respectively. The ellipticity in the far-UV obeyed triphasic kinetics. In
      addition to a rapid and a slow phase with rate constants similar to those
      observed in the near-UV, a "burst" of ellipticity was shown to occur in the dead
      time of the experiments. The effects of low pH and of concentrations of guanidine
      ranging from 0.075 to 1.5 M on the rapid and slow rate constants were studied.
      Under all conditions investigated, the rate constants observed in the far- and
      near-UV for a given phase were the same, thus suggesting that the molecular
      events observed in the two regions of the UV spectrum are either identical or
      strongly coupled. Continuous-flow experiments at different wavelengths between
      214 and 240 nm under conditions where the dead time for the observation was only
      4 ms, followed by a detailed analysis of the kinetics of ellipticity change at
      each wavelength, provided the spectrum of the molecular species formed at the end
      of the burst phase. This spectrum was found to closely fit that predicted from
      the secondary structure of native lysozyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390746
TI  - Spectroscopic analysis of a methionine-48 to tyrosine mutant of chicken troponin
      C.
AB  - A mutant (M48Y) of chicken skeletal muscle troponin C was prepared in which Tyr
      replaced Met-48 of the recombinant protein (rTnC). Since Tyr and Trp are normally
      absent, spectral properties could be unambiguously assigned to the site of
      substitution. In the crystal structure, this residue lies at the COOH-terminal
      end of the B-helix of the N domain in a region postulated to undergo a
      significant conformational change to a more polar environment upon Ca2+ binding
      [Herzberg et al. (1986) J. Biol. Chem. 261, 2638-2644]. Comparison of the far-UV
      CD spectra of M48Y and rTnC in the absence and presence of Ca2+ indicated no
      overall structural alteration due to the mutation. However, Ca2+ titration of the
      ellipticity change showed a reduction in Ca2+ affinity and cooperativity of sites
      I and II. A Ca(2+)-induced increase in the near-UV ellipticity of M48Y at pH 7.12
      and a red shift in its UV absorbance spectrum occurred over a range of free
      [Ca2+] attributable to the N-domain transition only. This was largely abolished
      at pH 5.3 where Ca2+ no longer binds to sites I and II. That region of the 1H NMR
      spectrum attributable to Tyr was broadened upon Ca2+ binding. These Ca(2+)
      induced changes are consistent with the environment of the Tyr side chain
      becoming chiral, less polar, and more immobile, all in a direction opposite to
      that predicted. These observations indicate that while the general features of
      the postulated model are valid, it is unlikely to be correct in detail.

PMID- 1390747
TI  - Reversible dimer dissociation of tubulin S and tubulin detected by fluorescence
      anisotropy.
AB  - Concentration-dependent dissociation of dimers of goat brain tubulin S and
      tubulin was studied by fluorescence anisotropy. Upon dilution, assembly-competent
      fluorescein 5'-maleimide labeled dimers of tubulin S and tubulin show a
      progressive decrease in fluorescence anisotropy. That this lowering of anisotropy
      results from the dissociation of tubulin S dimers into monomers was shown by
      dilution experiments with unlabeled homologous and heterologous proteins. A
      nonlinear least-squares fit of the data gave a dissociation constant of 7.1 x 10(
      8) M for tubulin S compared to 7.2 x 10(-7) M for tubulin at 25 degrees C in 0.1
      M PEM buffer, pH 7.0. van't Hoff plots of dimer-monomer dissociation of tubulin S
      and tubulin also show considerable differences in delta H and delta S. Effects of
      ionic strength and colchicine on the equilibrium constants are also substantially
      different for tubulin and tubulin S. The implications of these observations on
      the influence of C-terminal tails on tubulin structure are discussed.

PMID- 1390748
TI  - Differential scanning calorimetry of thermal unfolding of the methionine
      repressor protein (MetJ) from Escherichia coli.
AB  - The thermal stability of the methionine repressor protein from Escherichia coli
      (MetJ) has been examined over a wide range of pH (pH 3.5-10) and ionic strength
      conditions using differential scanning calorimetry. Under reducing conditions,
      the transitions are fully reversible, and thermograms are characteristic of the
      cooperative unfolding of a globular protein with a molecular weight corresponding
      to the MetJ dimer, indicating that no dissociation of this dimeric protein occurs
      before unfolding of the polypeptide chains under most conditions. In the absence
      of reducing agent, repeated scans in the calorimeter show only partial
      reversibility, though the thermodynamic parameters derived from the first scans
      are comparable to those obtained under fully reversible conditions. The protein
      is maximally stable (Tm 58.5 degrees C) at about pH 6, close to the estimated
      isoelectric point, and stability is enhanced by increasing ionic strength in the
      range I = 0.01-0.4 M. The average calorimetric transition enthalpy (delta Hm) for
      the dimer is 505 +/- 28 kJ mol-1 under physiological conditions (pH 7, I = 0.125,
      Tm = 53.2 degrees C) and shows a small temperature dependence which is consistent
      with an apparent denaturational heat capacity change (delta Cp) of about +8.9 kJ
      K-1 mol-1. The effects of both pH and ionic strength on the transition
      temperature and free energy of MetJ unfolding are inconsistent with any single
      amino acid contribution and are more likely the result of more general
      electrostatic interactions, possibly including significant contributions from
      electrostatic repulsion between the like-charged monomers which can be modeled by
      a Debye-Huckel screened potential.

PMID- 1390749
TI  - Synergistic inhibition of Escherichia coli aspartate transcarbamylase by CTP and
      UTP: binding studies using continuous-flow dialysis.
AB  - The allosteric control of Escherichia coli aspartate transcarbamylase (ATCase)
      involves feedback inhibition by both CTP and UTP, although it is only in the
      presence of CTP that UTP appears to inhibit the activity of the enzyme. In order
      to better understand the parts played by both pyrimidine nucleotides in this
      synergistic inhibition, binding studies were performed by continuous-flow
      dialysis and ultracentrifugation methods. The results obtained show that UTP
      binds to ATCase in the absence of CTP. Nevertheless, this binding does not induce
      any inhibition unless CTP is present. The mutual influence of CTP and UTP on
      their respective binding constants suggests that they bind to the same regulatory
      sites. However, the results obtained cannot be satisfactorily explained by a
      simple competition between the nucleotides, and it is shown that reciprocal
      affinity enhancements play a fundamental role. CTP enhances the affinity of UTP
      for the regulatory sites 80-fold, and conversely, UTP enhances the affinity of
      CTP 5-fold. Interestingly, the isolated regulatory subunits bind the two
      pyrimidine nucleotides following the same pattern as the entire enzyme. These
      observations indicate that the synergistic inhibition mechanism relies entirely
      on interactions between the two adjacent allosteric sites which belong to the
      same regulatory dimer.

PMID- 1390751
TI  - Characterization of C439SR1, a mutant of Escherichia coli ribonucleotide
      diphosphate reductase: evidence that C439 is a residue essential for nucleotide
      reduction and C439SR1 is a protein possessing novel thioredoxin-like activity.
AB  - Ribonucleotide reductase from Escherichia coli catalyzes the conversion of
      nucleotides to deoxynucleotides. Cysteine 439 is proposed to be the protein
      radical on R1 which initiates the reduction reaction by cleavage of the 3' carbon
      hydrogen bond of the nucleotide (Mao et al., 1992a,b). C439 is thus proposed to
      be essential for catalysis. The C439S mutant of R1 (C439SR1) was prepared. The
      structure of this mutant was determined to be similar to wt-R1, based on
      identical CD spectra, isolation via an affinity column specific for the
      allosteric binding domain, binding of the substrate GDP, and competition with R1
      for binding to R2. Preparations of C439SR1 are contaminated with low levels of wt
      R1 due to the expression system. The wt-R1 in these preparations can be
      specifically inactivated by the stoichiometric mechanism-based inhibitor, 2'
      azido-2'-deoxyuridine 5'-diphosphate. The activity of the resulting C439SR1 was
      shown to be less than 0.03% that of the corresponding wt-R1. This is the lower
      limit of detection with the present assay method. Thus C439 appears to be
      essential for catalysis. During these studies an unexpected activity of the
      C439SR1 was uncovered. Its additional cysteines, presumably C754 and C759, appear
      to function as a thioredoxin with the wt-R1, even though it is incapacitated with
      respect to nucleotide reduction.

PMID- 1390750
TI  - Interaction of C225SR1 mutant subunit of ribonucleotide reductase with R2 and
      nucleoside diphosphates: tales of a suicidal enzyme.
AB  - Ribonucleotide reductase (RDPR) from Escherichia coli is composed of two
      subunits, R1 and R2, both of which are required to catalyze the conversion of
      nucleotides to deoxynucleotides. This reduction process is accompanied by
      oxidation of two cysteines within the active site to a disulfide. One of these
      putative active site cysteines, C225, has been mutated to a serine, and the
      properties of this mutant (C225SR1) have been investigated in detail. Incubation
      of C225SR1 and R2 with [3'-3H,U-14C]UDP results in time-dependent inactivation of
      the enzyme! This inactivation is accompanied by production of 2.4 uracils, 3H2O,
      and 3H,14C-labeled protein with an absorbance change at 320 nm. There is an
      isotope effect (kH/k3H) on uracil production of 3.2. In addition, the tyrosyl
      radical on R2 is reduced. The observation of 3H2O, indicative of 3' carbon
      hydrogen bond cleavage and loss of the tyrosyl radical, provides a direct test of
      our mechanistic hypothesis that cleavage of this bond occurs concomitantly with
      tyrosyl radical reduction. Incubation of [3'-2H]UDP with C225SR1 and R2 resulted
      in a V and V/K isotope effect on loss of the radical of 2.0 and 2.0,
      respectively. These studies provide the first direct evidence for protein radical
      involvement in catalysis. Reduction of the tyrosyl radical on R2 is accompanied
      by a stoichiometric cleavage of the R1 polypeptide into two new polypeptides of
      26 and 61 kDa. The 26-kDa polypeptide is the N-terminus of R1, and hence cleavage
      of the polypeptide is occurring in the region of the mutation. The N-terminus of
      the 61-kDa polypeptide is blocked.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390752
TI  - 3-Carboxy-cis,cis-muconate lactonizing enzyme from Pseudomonas putida is
      homologous to the class II fumarase family: a new reaction in the evolution of a
      mechanistic motif.
AB  - The gene (pcaB) for 3-carboxymuconate lactonizing enzyme (CMLE; 3-carboxymuconate
      cycloisomerase; EC 5.5.1.2) from Pseudomonas putida has been cloned into pMG27NS,
      a temperature-sensitive expression vector, and expressed in Escherichia coli
      N4830. The specific activity and kinetic parameters of the recombinant CMLE were
      comparable to those previously reported. A comparison of the deduced amino acid
      sequence of CMLE with sequences available in the PIR and Genbank databases
      revealed that CMLE has highly significant sequence homology to the class II
      fumarase family, particularly to adenylosuccinate lyase from Bacillus subtilis.
      CMLE has no significant homology to muconate lactonizing enzyme (MLE) from P.
      putida, its sister enzyme in the beta-ketoadipate pathway. These findings fully
      corroborate a prediction made by us on the basis of mechanistic and
      stereochemical analyses of CMLE and MLE [Chari, R. V. J., Whitman, C. P.,
      Kozarich, J. W., Ngai, K.-L., & Ornston, L. N. (1987) J. Am. Chem. Soc. 109, 5514
      5519] and suggest that CMLE and MLE were recruited into this specialized pathway
      from two different enzyme families.

PMID- 1390753
TI  - Conferral of malonyl coenzyme A sensitivity to purified rat heart mitochondrial
      carnitine palmitoyltransferase.
AB  - An immunoaffinity column against the 86-kDa malonyl-CoA-binding protein of beef
      heart mitochondria was prepared, and the properties of the eluates were compared
      to those of eluates of an anti-carnitine palmitoyltransferase immunoaffinity
      column. Both eluates contain seven to eight major proteins with a malonyl-CoA
      binding capacity of approximately 5 nmol/mg of protein; in contrast, the eluates
      from a preimmune IgG column did not contain any of the major proteins. The
      eluates from both immunoaffinity columns conferred malonyl-CoA sensitivity to
      purified rat heart mitochondrial carnitine palmitoyltransferase (CPTi/CPT-II).
      Addition of phospholipids increased the degree of malonyl-CoA inhibition.
      Doubling the amount of column eluate approximately doubled the malonyl-CoA
      sensitivity when added to a fixed amount of CPT; i.e., the inhibition increased
      from 32 to 67%. These results show that CPTi/CPT-II is capable of exhibiting
      malonyl-CoA sensitivity in the presence of malonyl-CoA-binding proteins. The
      results do not support the concept that the 86-kDa malonyl-CoA-binding protein is
      detergent-inactivated carnitine palmitoyltransferase I;rather, they suggest that
      it is a regulatory subunit of a carnitine palmitoyltransferase complex.

PMID- 1390754
TI  - Active site structure of methylamine dehydrogenase: hydrazines identify C6 as the
      reactive site of the tryptophan-derived quinone cofactor.
AB  - To identify the reactive part of the orthoquinone function of the tryptophan
      derived cofactor found in methylamine dehydrogenase (MADH), we have determined
      the crystal structures of MADH from Thiobacillus versutus inhibited by
      methylhydrazine and (2,2,2-trifluoroethyl)hydrazine. Extra electron density
      attached to C6 of the tryptophyl tryptophanquinone cofactor shows that this atom
      and not C7 is the reactive part of the ortho-quinone moiety. The density retained
      after hydrazine inhibition is much less extensive than expected, however,
      suggesting that partial breakdown of the inhibitors after reaction with the
      cofactor may take place. A detailed description is presented of the cofactor
      environment in an improved model of MADH which now includes information from the
      recently determined gene sequence of the cofactor-containing subunit [Ubbink, M.,
      van Kleef, M.A.G., Kleinjan, D., Hoitink, C.W.G., Huitema, F., Beintema, J.J.,
      Duine, J.A., & Canters, G.W. (1991) Eur. J. Biochem. 202, 1003-1012]. We
      hypothesize that Asp76 is responsible for proton abstraction from the alpha
      carbon of the substrate during catalysis.

PMID- 1390755
TI  - Refined atomic model of wheat serine carboxypeptidase II at 2.2-A resolution.
AB  - The crystal structure of the homodimeric serine carboxypeptidase II from wheat
      (CPDW-II, M(r) 120K) has been determined and fully refined at 2.2-A resolution to
      a standard crystallographic R factor of 16.9% using synchrotron data collected at
      the Brookhaven National Laboratory. The model has an rms deviation from ideal
      bond lengths of 0.018 A and from bond angles of 2.8 degrees. The model supports
      the general conclusions of an earlier study at 3.5-A resolution and will form the
      basis for investigation into substrate binding and mechanistic studies. The
      enzyme has an alpha + beta fold, consisting of a central 11-stranded beta-sheet
      with a total of 15 helices on either side. The enzyme, like other serine
      proteinases, contains a "catalytic triad" Ser146-His397-Asp338 and a presumed
      "oxyanion hole" consisting of the backbone amides of Tyr147 and Gly53. The
      carboxylate of Asp338 and imidazole of His397 are not coplanar in contrast to the
      other serine proteinases. A comparison of the active site features of the three
      families of serine proteinases suggests that the "catalytic triad" should
      actually be regarded as two diads, a His-Asp diad and a His-Ser diad, and that
      the relative orientation of one diad with respect to the other is not
      particularly important. Four active site residues (52, 53, 65, and 146) have
      unfavorable backbone conformations but have well-defined electron density,
      suggesting that there is some strain in the active site region. The binding of
      the free amino acid arginine has been analyzed by difference Fourier methods,
      locating the binding site for the C-terminal carboxylate of the leaving group.
      The carboxylate makes hydrogen bonds to Glu145, Asn51, and the amide of Gly52.
      The carboxylate of Glu145 also makes a hydrogen bond with that of Glu65,
      suggesting that one or both may be protonated. Thus, the loss of peptidase
      activity at pH > 7 may in part be due to deprotonation of Glu145. The active site
      does not reveal exposed peptide amides and carbonyl oxygen atoms that could
      interact with substrate in an extended beta-sheet fashion. The fold of the
      polypeptide backbone is completely different than that of trypsin or subtilisin,
      suggesting that this is a third example of convergent molecular evolution to a
      common enzymatic activity. Furthermore, it is suggested that the active site
      sequence motif "G-X-S-X-G/A", often considered the hallmark of serine peptidase
      or esterase activity, is fortuitous and not the result of divergent
      evolution.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1390756
TI  - Oligosaccharide structures of the major exoglucanase secreted by Saccharomyces
      cerevisiae.
AB  - We have determined the structures of the N-linked carbohydrate chains, released
      by endo H, of exoglucanase II that are secreted by wild-type Saccharomyces
      cerevisiae and by the mnn1 mnn9 and mnn1 glycosylation mutants. The mnn9 mutation
      does not significantly affect N-linked oligosaccharides of exoglucanase II since
      we found almost identical structures in both mutant strains consisting of a
      slightly enlarged core with the basic structure shown in A (where M = mannose).
      Most of the molecules (77%) were phosphorylated on one of the starred mannoses
      (34%) or on both (43%) with a diesterified (alpha M-->P-->) or monoesterified
      phosphate group. In addition, some of the molecules apparently escape normal
      processing and retain the alpha-(1-->2)-linked mannose (italicized) and/or the
      three glucoses that are characteristic of the lipid-linked precursor (structure
      B). In the wild type, we found the same basic structure but more [formula; see
      text] than 90% of the molecules were modified with one to four alpha-(1-->3)
      linked mannoses, which were absent in the strains bearing the mnn1 mutation
      (structure C). The proportion of acidic components was similar to that found in
      the mutants (78%), although, in this case, the monophosphorylated forms were more
      abundant (50%) than the diphosphorylated ones (28%). Most of the phosphate groups
      (69%) were diesterified by a disaccharide (alpha M-->3 alpha M-->P-->) instead of
      the single mannose found when the mnn1 mutation was present. In both mnn1 and
      wild type 10-15% of the oligosaccharides had an extra alpha-(1-->6)-linked
      mannose in the outer chain, a structure described in the recently isolated vrg1
      mutant [Ballou, L., Hitzeman, R.A., Lewis, M. S., & Ballou, C. E. (1991) Proc.
      Natl. Acad. Sci. U.S.A. 88, 3209-3212].

PMID- 1390757
TI  - Structural elucidation of a novel family of acyltrehaloses from Mycobacterium
      tuberculosis.
AB  - Analysis of the lipids of Mycobacterium tuberculosis H37Rv, by both normal- and
      reverse-phase thin-layer chromatography, revealed a series of novel glycolipids
      based on 2,3-di-O-acyltrehalose. The structures of these acylated trehaloses were
      elucidated by a combination of gas chromatography-mass spectrometry, 1H, 13C, two
      dimensional 1H-1H, and 1H-13C nuclear magnetic resonance spectrometry. The fatty
      acyl substituents were mainly of three types: saturated straight-chain C16-C19
      acids; C21-C25 "mycosanoic acids"; and C24-C28 "mycolipanolic acids." Analysis of
      one of the major 2,3-di-O-acyltrehaloses by two-dimensional 1H-chemical shift
      correlated and 1H-detected heteronuclear multiple-bond correlation spectroscopy
      established that the C18 saturated straight-chain acyl group was located at the 2
      position and that the C24 mycosanoyl substituent was at the 3 position of the
      same "right-hand" glucosyl residue. At least six molecular species differing only
      in their fatty acid content comprised this family of di-O-acylated trehaloses. We
      regard these acyltrehaloses as elemental forms of the multiglycosylated
      acyltrehaloses (the lipooligosaccharides) perhaps due to an inability of the
      majority of isolates of virulent tubercle bacilli to glycosylate core
      acyltrehaloses. The acyltrehaloses are minor but consistent components of
      virulent M. tuberculosis and apparently the basis of the specific serological
      activity long associated with its lipid fractions.

PMID- 1390758
TI  - Effect of membrane fluidity and fatty acid composition on the prothrombin
      converting activity of phospholipid vesicles.
AB  - Vesicles composed of phospholipids with different fatty acyl side chains have
      been utilized to examine the importance of the nonpolar membrane region for the
      prothrombin-converting activity of procoagulant phospholipid vesicles. Membranes
      composed of phosphatidylserine (PS) and phosphatidylcholine (PC) with unsaturated
      fatty acyl side chains were more active in prothrombin activation than membranes
      composed of phospholipids with saturated fatty acyl chains. This phenomenon was
      observed above the phase transition temperature, i.e., on membranes in the liquid
      crystalline state. The prothrombin-converting activity of saturated phospholipids
      approached the activity of unsaturated phospholipids at high factor Va
      concentrations, which is indicative for a less favorable equilibrium constant for
      prothrombinase assembly on membrane surfaces composed of saturated phospholipids.
      The difference between saturated and unsaturated phospholipids was annulled on
      membranes with high mole percentages of PS. This may result from a compensating
      contribution of electrostatic forces to the binding equilibria involved in
      prothrombinase assembly. Additional effects on the prothrombin-converting
      activity were observed when membranes containing saturated phospholipids were
      studied below their phase transition temperature. In agreement with Higgins et
      al. [(1985) J. Biol. Chem. 260, 3604-3612], we found that the time required for
      the assembly of prothrombinase from membrane-bound factors Xa and Va is
      considerably prolonged on solid membranes. However, we also observed an effect of
      membrane fluidity on the steady-state rate of prothrombin activation. Kinetic
      experiments at saturating factor Va concentrations showed that the transition
      from the liquid-crystalline to the gel state caused a more than 9-fold decrease
      of the kcat of prothrombin activation without affecting the Km for
      prothrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390759
TI  - Detection of internal motions in oligosaccharides by 1H relaxation measurements
      at different magnetic fields.
AB  - The effect of internal motions on proton relaxation data in oligosaccharides has
      been investigated experimentally. 1H steady-state and transient NOEs together
      with 13C T1's have been measured at two magnetic field strengths. The existence
      of internal motions leads to additional modulations of the dipolar interaction
      between proton pairs, thus producing a range of spectral density functions for
      these interactions. As a result, it is possible to show that protons relaxing
      through fixed distances have a different ratio of relaxation parameters, acquired
      at 500 and 300 MHz, compared to those relaxing through fluctuating distances.
      This approach has been used to unequivocally establish for two disaccharides the
      existence of internal motions on the time scale of the overall tumbling.

PMID- 1390760
TI  - Conformational changes in phospholipase A2 upon binding to micellar interfaces in
      the absence and presence of competitive inhibitors. A 1H and 15N NMR study.
AB  - An NMR study has been made of porcine pancreatic phospholipase A2 (PLA) in three
      environments: free in solution, in a binary complex with dodecylphosphocholine
      micelles, and in a ternary complex with a micelle and the substrate-like
      inhibitor (R)-1-octyl-2-(N-dodecanoylamino)-2-deoxyglycero-3-phosph oglycol. 1H
      and 15N chemical shifts, amide exchange rates, and NOE intensities are compared
      for the enzyme in different environments. From these data, structural differences
      are found for the N-terminal part, the end of the surface loop at residues Tyr69
      and Thr70, and the active site residue His48, and also for the Ca-binding loop
      (residues 28-32). Specifically, when binding to a micelle, the side chains of
      residues Ala1, Trp3, and Tyr69, as well as all protons of Thr70, are found to be
      closer together. After subsequent introduction of the competitive inhibitor,
      further changes are found for these residues. The N-terminus is flexible in PLA
      free in solution, in contrast with the crystal structures where it adopts an
      alpha-helical conformation. According to the NMR data, this helix is rigidly
      formed only in the ternary complex. Furthermore, in the ternary complex, the N
      terminal amino group and the exchangeable hydrogen at N3 of the ring of His48 are
      observed. We propose that PLA is activated in two steps. An initial
      conformational change occurs upon binding to a micellar interface. The
      catalytically active conformation of the enzyme, which has an extensive network
      of hydrogen bonds, is formed only when binding a substrate or competitive
      inhibitor at a lipid-water interface.

PMID- 1390761
TI  - Response of the phosphatidylcholine headgroup to membrane surface charge in
      ternary mixtures of neutral, cationic, and anionic lipids: a deuterium NMR study.
AB  - Deuterium nuclear magnetic resonance (2H NMR) spectroscopy was used to
      investigate the response of the phosphatidylcholine headgroup of 1,2-dimyristoyl
      sn-glycero-3-phosphocholine (DMPC) to changes in surface electrostatic charge in
      membranes consisting of ternary mixtures of lipids. DMPC was deuterated at the
      choline alpha- and beta-methylene segments. The membrane surface charge was
      manipulated by the simultaneous addition of cationic didodecyldimethylammonium
      bromide (DDAB) and anionic 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) to
      neutral DMPC. Addition of increasing amounts of DDAB caused a progressive
      decrease (increase) in the 2H NMR quadrupole splitting from DMPC-alpha-d2 (DMPC
      beta-d2). Addition of increasing amounts of DMPG caused a progressive increase
      (decrease) in the quadrupole splitting from DMPC-alpha-d2 (DMPC-beta-d2).
      Qualitatively, the 2H NMR quadrupole splitting charge response exhibited the same
      main features for ternary mixtures of DDAB/DMPG/DMPC and binary mixtures of
      DDAB/DMPC or DMPG/DMPC. Quantitatively, however, the 2H NMR quadrupole splittings
      obtained from ternary mixtures did not coincide with those obtained from binary
      mixtures of nominally identical surface charge densities. Hence, the quadrupole
      splitting did not respond directly to the net membrane surface charge. Instead,
      the quadrupole splitting measured for a given ternary lipid composition could be
      reproduced by summing the individual effects of the charged lipids in binary
      mixtures, weighted according to their appropriate mole fractions.

PMID- 1390762
TI  - Influence of lipid composition on the orientational order in Acholeplasma
      laidlawii strain B membranes: a deuterium NMR study.
AB  - 2H NMR techniques have recently been developed to determine the complete
      orientational order profile of lipid bilayers employing lipids containing
      perdeuteriated palmitic acid [Lafleur, M., Fine, B., Sternin, E., Cullis, P.R., &
      Bloom, M. (1989) Biophys. J. 56, 1037-1041]. In this work, these techniques have
      been applied to study order profiles in intact membranes derived from
      Acholeplasma laidlawii strain B. It is shown that complete orientational order
      profiles can be readily obtained from the intact membranes of A. laidlawii B
      grown on equimolar amounts of perdeuteriated palmitic acid and a nondeuteriated
      fatty acid of varying length and unsaturation. By variation of the fatty acid
      composition employing mixtures of perdeuteriated palmitic acid with myristic,
      elaidic, oleic, or linoleic acid, a range of hydrocarbon order compatible with
      high rates and extents of cell growth has been obtained where the average order
      parameter, mean value of S, varies over the range 0.140-0.176. This same
      variation in order is seen for liposomes derived from total lipids extracted from
      these intact membranes. 2H NMR studies on liposomes composed of individual
      species of the extracted lipids indicate that modulation of the membrane lipid
      headgroup composition has the potential to play an important role in maintaining
      the membrane order within this range.

PMID- 1390764
TI  - Binding between maleimidobenzoyl-G-actin and myosin subfragment 1.
AB  - It is well known that the structural interactions between S-1 moieties of myosin
      molecules ("cross bridges") and actin molecules in polymerized ("F") form are
      thought to underlie muscle contraction. It is surmised that such interactions are
      unitary (actin:S-1 = 1:1), but actual demonstration thereof is handicapped by
      intrinsic properties of the proteins. Recently, it has been reported that
      chemically modified [with m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS)]
      actin maintains its monomeric ("G") form and makes a stable unitary complex with
      S-1 but does not activate the S-1 ATPase [Bettache, N., Bertrand, R., & Kassab,
      R. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6028-6032]. However, we recently
      showed that when MBS-G-actin and S-1 are covalently cross-linked by 1-ethyl-3-[3
      (dimethylamino)propyl]-carbodiimide (EDC), ATPase activity is restored [Hozumi,
      T. (1991) Biochem. Int. 23, 835-843]. Here we investigated the interface between
      MBS-G-actin and S-1 using the techniques of tryptic digestion and EDC-cross
      linking. MBS-G-actin specifically protected the N-terminal region of S-1 heavy
      chain against tryptic cleavage at the 25 kDa/50 kDa junction, which is different
      from the effect that a protomer within F-actin has on the protection of the 25
      kDa/50 kDa junction. In addition, the cross-linking pattern between MBS-G-actin
      and S-1 was different from that between F-actin and S-1. When MBS-G actin was
      cross-linked to trypsin-treated S-1, no cross-linked product was
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390763
TI  - Peptide binding to lipid bilayers. Nonclassical hydrophobic effect and membrane
      induced pK shifts.
AB  - The binding of the cyclic peptide (+)-D-Phe1-Cys2-Phe3-D-Trp4-(+)-Lys5-Thr6- Cys7
      Thr(ol)8, a somatostatin analogue (SMS 201-995), and the potential-sensitive dye
      2-(p-toluidinyl)naphthalene-6-sulfonate (TNS) to lipid membranes was investigated
      with high-sensitivity titration calorimetry. The binding enthalpy of the peptide
      was found to vary dramatically with the vesicle size. For highly curved vesicles
      with a diameter of d congruent to 30 nm, the binding reaction was enthalpy-driven
      with delta H congruent to -7.0 +/- 0.3 kcal/mol; for large vesicles with more
      tightly packed lipids, the binding reaction became endothermic with delta H
      congruent to +1.0 +/- 0.3 kcal/mol and was entropy-driven. In contrast, the free
      energy of binding was almost independent of the vesicle size. The thermodynamic
      analysis suggests that the observed enthalpy-entropy compensation of about 8
      kcal/mol can be related to a change in the internal tension of the bilayer and is
      brought about by an entropy increase of the lipid matrix. The "entropy potential"
      of the membrane may have its molecular origin in the excitation of the
      hydrocarbon chains to a more disordered configuration and may play a more
      important role in membrane partition equilibria than the classical hydrophobic
      effect. The binding of the peptide to the membrane surface induced a pK shift of
      the peptide terminal amino group. Neutral membranes were found to destabilize the
      NH3+ group, leading to a decrease in pK; negatively charged membranes, generated
      an apparent increase in pK due to the increase in proton concentration near the
      membrane surface. No pK shifts were seen for TNS. Titration calorimetry combined
      with the Gouy-Chapman theory can be used to determine both the reaction enthalpy
      and the binding constant of the membrane-binding equilibrium.

PMID- 1390765
TI  - Oxygen binding constants and stepwise enthalpies for human and bovine hemoglobin
      at pH 7.6.
AB  - A high-precision thin-layer gas-solution microcalorimeter has been developed to
      study the binding reactions of gaseous ligands with ligand-binding macromolecules
      in a manner analogous to that of the Gill thin-layer optical apparatus [Doleman &
      Gill (1976) Anal. Biochem. 87, 127]. We have generated differential heat-binding
      curves of oxygen binding to human and bovine hemoglobin in phosphate buffer at pH
      7.6, with the enzyme-reducing system of Hayashi et al. [(1973) Biochim. Biophys.
      Acta 310, 309]. Experiments were conducted at a number of different temperatures
      in order to expand the data field, allowing for separation of enthalpy and free
      energy parameters. This type of experimental analysis makes no assumptions of
      optical linearity between the various heme groups and reveals that the triply
      ligated species is measurably significant for both human and bovine hemoglobin.
      It was also determined that the concentration of doubly ligated species of bovine
      hemoglobin is relatively low. The experiments indicate that the reactions for
      both hemoglobins are enthalpy-driven for oxygen stepwise additions 1, 2, and 4
      while being entropy-driven for step 3. Human hemoglobin oxygen-binding
      experiments were also performed with the Gill thin-layer optical apparatus under
      solution conditions identical to those used in the calorimeter. The experiments
      revealed that if optical linearity is assumed, the overall third equilibrium
      constant is negative or near zero. This indicated that either the optical cell's
      performance is much poorer than the thin-layer calorimeter or there is an
      appreciable nonlinear optical effect.

PMID- 1390766
TI  - Synthetic analogs of the carboxyl-terminus of beta-thyrotropin: the importance of
      basic amino acids in receptor binding activity.
AB  - Previously, using a synthetic peptide strategy, we determined that four distinct
      regions of human beta-thyrotropin (beta TSH) were responsible for interaction of
      TSH with the TSH receptor. The most potent of these four regions was the carboxyl
      terminus of the subunit, represented by the peptide sequence beta 101-112, which
      inhibited binding of radiolabeled beta TSH to receptor in radioreceptor assay
      with an IC50 of approximately 100 microM. In the current studies, we
      systematically substituted the native amino acids in region beta 101-112 with
      alanine, and we have determined which residues within this span are important to
      the binding activity of TSH to its receptor. Substitution of Lys101, Asn103,
      Tyr104, Cys105, Lys107, and Lys110 with alanine each caused a significant fall in
      activity as compared to the native sequence, whereas substitution at the
      remaining positions had little or no effect. Because three of these residues are
      positively charged at physiologic pH, we hypothesized that this charge may be
      important to the binding activity of the sequence. We modified the charge
      characteristics of the region by synthesizing two series of analogs in which the
      residues identified in the alanine substitution studies were substituted with
      Arg, D-Lys, and D-Arg at each position. In addition, a series of analogs
      containing basic residues, either added to or substituted for nonbasic residues
      in the sequence beta 101-112, was synthesized. Substitution of Arg, D-Lys, and D
      Arg for Lys101, Lys107, and Lys110 had little effect on activity; however,
      inclusion of additional basic residues in the beta 101-112 sequence significantly
      enhanced the inhibitory activity of the region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390767
TI  - Acetyladenylate or its derivative acetylates the chemotaxis protein CheY in vitro
      and increases its activity at the flagellar switch.
AB  - CheY, a key protein in the mechanism of bacterial chemotaxis, is known to
      interact with the flagellar switch and thereby cause clockwise rotation. This
      activity of CheY was significantly increased by producing acetyladenylate (AcAMP)
      within cytoplasm-free bacterial envelopes containing purified CheY. This was
      achieved by including in the envelopes the enzyme acetyl-CoA synthetase (ACS) and
      ATP, and adding acetate externally. The fraction of clockwise-rotating envelopes,
      tethered to glass by their flagella, increased from 14% to 58% by the presence of
      AcAMP (or its derivative). In parallel experiments carried out with [14C]acetate
      under similar conditions, CheY became acetylated: [1-14C]acetate was as effective
      as [2-14C]acetate in labeling CheY, and ACS-dependent labeling of CheY by [alpha
      32P]ATP was not detected. The switch proteins, FliG, FliM, and FliN, isolated to
      purity, were not acetylated. The acetylation was specific for CheY and dependent
      on its native conformation. The acetylated form the CheY was estimated to be more
      active than its nonacetylated form by 4-5 orders of magnitude. Acetylated CheY
      was stable in the presence of the strong nucleophiles hydroxylamine or
      ethanolamine, indicative of N-acetylation. There was a correlation between the
      activity of CheY in vivo and its ability to be acetylated in vitro. Thus,
      proteins with a single substitution at their active site, CheY57DE and CheY109KR,
      are not active in vivo and accordingly were not acetylated in vitro; in contrast,
      the protein CheY13DK is active in vivo and was normally acetylated in vitro. The
      possibility that CheY acetylation plays a role in bacterial chemotaxis is
      discussed.

PMID- 1390768
TI  - 31P NMR and X-ray diffraction study of the effect of photopolymerization on lipid
      polymorphism.
AB  - It was recently shown that oligolamellar vesicles of 3:1 mixtures of
      dioleoylphosphatidylethanolamine (DOPE) and the photopolymerizable lipid 1,2
      bis[10-(2',4'-hexadienoyloxy)decanoyl]-sn-glycero-3-phosphocho line (SorbPC) are
      destabilized by polymerization of the SorbPC [Lamparski, H., Liman, U., Frankel,
      D.A., Barry, J.A., Ramaswami, V., Brown, M.F., & O'Brien, D.F. (1992)
      Biochemistry 31, 685-694]. The current work describes the polymorphic phase
      behavior of these mixtures in extended bilayers, as studied by 31P NMR
      spectroscopy and X-ray diffraction. In the NMR experiments, samples with varying
      degrees of polymerization were slowly raised in temperature, with spectra
      acquired every 2.5-10 degrees C. In the unpolymerized mixiture, and in those
      photopolymerized samples where the monomeric SorbPC was decreased by 33% and 51%,
      an isotropic signal grew progressively until no signal from the lamellar liquid
      crystalline (L alpha) phase remained. In the highly polymerized sample with a 90%
      loss of monomeric SorbPC, less than 20% of the lipids underwent this transition.
      In none of the samples was an inverted hexagonal phase (HII) observed, under
      conditions of slow heating to almost 100 degrees C. The X-ray diffraction studies
      indicated that samples which exhibit the isotropic NMR signal corresponded to a
      structure exhibiting no well-defined crystalline order, which upon thermal
      cycling became an inverted cubic phase belonging to either the Pn3m or Pn3 space
      groups. The temperature of the transition to the cubic precursor decreased as the
      extent of polymerization increased, demonstrating that photopolymerization of
      these lipid bilayers can significantly alter the composition and thermotropic
      phase behavior of the mixture.

PMID- 1390769
TI  - Water as ligand: preferential binding and exclusion of denaturants in protein
      unfolding.

PMID- 1390770
TI  - Role of glycosylation on the secretion and biological activity of erythropoietin.
AB  - The erythropoietin (EPO) molecule contains four carbohydrate chains. Three
      contain N-linkages to asparagines at positions 24, 38, and 83, and one contains
      an O-linkage to a serine at position 126. We constructed human EPO variants that
      eliminated the three N-glycosylation sites by replacing the asparagines with
      glutamines singly or in combination. The O-linked carbohydrate chain was removed
      by replacing the serine with glutamine, valine, histidine, or alanine. A variant
      with a double mutation (Gln38,83) and another with a triple mutation
      (Gln24,38,83) were secreted poorly from COS1 and CHO cells even though RNA
      encoding these variants was present. All other variants with mutations in N
      linked glycosylation sites were secreted normally. Removal of any of the N
      glycosylation sites reduced the in vivo but not the in vitro biological activity
      of the EPO molecule. All the mutations at Ser126, the O-glycosylation site, were
      secreted normally. In vitro activity was also unaffected except for Ala126 which
      had a 50-fold decrease. The Val126 variant was tested in vivo, and its specific
      activity was only slightly less than that of the native EPO, which indicates that
      the O-linked carbohydrate is not essential for activity.

PMID- 1390771
TI  - Structural basis for recognition of polyglutamyl folates by thymidylate synthase.
AB  - Thymidylate synthase (TS) catalyzes the final step in the de novo synthesis of
      thymidine. In vivo TS binds a polyglutamyl cofactor, polyglutamyl
      methylenetetrahydrofolate (CH2-H4folate), which serves as a carbon donor.
      Glutamate residues on the cofactor contribute as much as 3.7 kcal to the
      interaction between the cofactor, substrate, and enzyme. Because many
      ligand/receptor interactions appear to be driven largely by hydrophobic forces,
      it is surprising that the addition of hydrophilic, soluble groups such as
      glutamates increases the affinity of the cofactor for TS. The structure of a
      polyglutamyl cofactor analog bound in ternary complex with deoxyuridine
      monophosphate (dUMP) and Escherichia coli TS reveals how the polyglutamyl moiety
      is positioned in TS and accounts in a qualitative way for the binding
      contributions of the different individual glutamate residues. The polyglutamyl
      moiety is not rigidly fixed by its interaction with the protein except for the
      first glutamate residue nearest the p-aminobenzoic acid ring of folate. Each
      additional glutamate is progressively more disordered than the previous one in
      the chain. The position of the second and third glutamate residues on the protein
      surface suggests that the polyglutamyl binding site could be utilized by a new
      family of inhibitors that might fill the binding area more effectively than
      polyglutamate.

PMID- 1390772
TI  - Oligomerization of the cytoplasmic fragment from the aspartate receptor of
      Escherichia coli.
AB  - We have observed that a 31-kDa cloned fragment from the Escherichia coli
      aspartate receptor exhibits a reversible monomer-oligomer reaction. The fragment,
      derived from the cytoplasmic region of the receptor (c-fragment), contains the
      signaling functions of the receptor. The wild-type and nine missense mutant
      fragments were analyzed. The latter were selected by the effect of the mutations
      on the signaling properties of the intact receptor, which induced either
      persistent smooth swimming or tumbling in bacteria [Mutoh, N., Oosawa, K., &
      Simon, M. I. (1986) J. Bacteriol. 167, 992-998]. In pH 7.0 buffer, the mutations
      caused five out of the six smooth mutant c-fragments to form oligomers, while
      neither the three tumble mutant nor wild-type fragments exhibited significant
      oligomer formation. At a lower pH (5.5), all of the fragments displayed some
      tendency to form oligomers. The equilibria between the monomer and the oligomers
      were monitored by gel permeation chromatography (GPC) which resolved two to three
      forms with apparent molecular weights between 110,000 and 270,000. The
      proportions of the different forms depended on concentration, indicating an
      association-dissociation reaction. Static light scattering (SLS) was used to
      demonstrate that the solution molecular mass of the wild-type c-fragment was 31
      kDa and not 110 kDa as indicated by chromatography. One oligomer-forming c
      fragment (S461L) eluted as the monomer and one other form, which was determined
      to be a dimer by SLS. The weight-average molecular weights, calculated from GPC
      data as a function of protein concentration, agreed well with the weight-average
      molecular weights obtained by SLS for this mutant.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1390773
TI  - Mechanism of magainin 2a induced permeabilization of phospholipid vesicles.
AB  - The magainins, peptide antibiotics secreted by the frog Xenopus laevis, have
      previously been shown to permeabilize phospholipid vesicles. To elucidate the
      mechanism of permeabilization, we have conducted detailed kinetic studies of
      magainin 2 amide (mgn2a)-induced release of 6-carboxyfluorescein from vesicles of
      phosphatidylserine. The results show that dye release occurs in (at least) two
      stages--an initial rapid phase, with t1/2 approximately 3 s, followed by a much
      slower phase that approaches zero leakage rate before all the dye is released.
      Light-scattering studies showed that mgn2a does not cause gross changes in
      vesicle structure. The peptide was found to rapidly equilibrate between vesicles;
      this was demonstrated by determining a binding isotherm for the peptide-lipid
      interaction, and by showing that addition of unloaded vesicles rapidly quenches
      peptide-induced leakage from loaded vesicles. Transient dye release in the
      presence of an equilibrating peptide can be explained in two ways: (1) the
      peptide exists only transiently in an active form; (2) the vesicles are only
      transiently leaky. Preincubation of mgn2a at assay concentrations in buffer alone
      or with unloaded vesicles did not inactivate the peptide. Therefore, rapid
      leakage is probably due to transient destabilization of the vesicle upon addition
      of mgn2a.

PMID- 1390774
TI  - Novel alpha- and omega-conotoxins from Conus striatus venom.
AB  - Three neurotoxic peptides from the venom of Conus striatus have been purified,
      biochemically characterized, and chemically synthesized. One of these, an
      acetylcholine receptor blocker designated alpha-conotoxin SII, has the sequence
      GCCCNPACGPNYGCGTSCS. In contrast to all other alpha-conotoxins, SII has three
      disulfide bonds (instead of two), has no net positive charge, and has a free C
      terminus. The other two paralytic peptides are Ca channel-targeted omega
      conotoxins, SVIA and SVIB. omega-SVIA is the smallest natural omega-conotoxin so
      far characterized and has the sequence CRSSGSPCGVTSICCGRCYRGKCT-NH2. Although
      omega-conotoxin SVIA is a potent paralytic toxic in lower vertebrate species, it
      was much less effective in mammals. The third toxin, omega-conotoxin SVIB, has
      the sequence CKLKGQSCRKTSYDCCSGSCGRSGKC-NH2. This peptide has a different
      pharmacological specificity from other omega-conotoxins previously purified from
      Conus venoms; only omega-conotoxin SVIB has proven to be lethal to mice upon ic
      injection. Binding competition experiments with rat brain synaptosomal membranes
      indicate that the high-affinity binding site for omega-conotoxin SVIB is distinct
      from the high-affinity omega-conotoxin GVIA or MVIIA site.

PMID- 1390775
TI  - The two polypeptide chains in fibronectin are joined in antiparallel fashion: NMR
      structural characterization.
AB  - The fibronectin C-terminal interchain disulfide-linked heptapeptide dimer (Val
      Asn-Cys-Pro-Ile-Glu-Cys)2 has been investigated via 1H NMR spectroscopy in both
      water and dimethyl sulfoxide (DMSO) solutions. Proton Overhauser experiments in
      DMSO indicate unambiguously that the two fibronectin polypeptide chains are
      linked head-to-tail (N-terminus to C-terminus), in an antiparallel fashion. It is
      found that the structure of the peptide is extended. From the 1H NMR interproton
      distance and angle constraints, the preferred mean (time-averaged) conformations
      in both H2O and DMSO were derived using distance geometry and molecular mechanics
      algorithms. The two conformations, although significantly dissimilar, exhibit the
      common feature of a structurally parallel (as opposed to chemically antiparallel)
      fibronectin alpha/beta chain array.

PMID- 1390776
TI  - Regulation of the chromaffin granule aggregating activity of annexin I by
      phosphorylation.
AB  - Annexin I (lipocortin I) binds to secretory granule membranes and promotes their
      aggregation in a Ca(2+)-dependent manner [Creutz, C. E., et al. (1987) J. Biol.
      Chem. 262, 1860-1868; Drust, D. S., & Creutz, C. E. (1988) Nature 331, 88-91]. It
      is also phosphorylated on serine residues when bovine chromaffin cells are
      stimulated to secrete [Michener, M. L., et al. (1986) J. Biol. Chem. 261, 6548
      6555], suggesting phosphorylation may be involved in modulating the function of
      annexin I. We report here that phosphorylation of the N-terminal tail by protein
      kinase C strongly inhibits the ability of annexin I to aggregate chromaffin
      granules by increasing the calcium requirement 4-fold. This inhibition was
      readily reversed when the protein was dephosphorylated by protein phosphatase 2A.
      The inhibition was not due to inability of phosphorylated annexin I to bind to
      chromaffin granules, since the phosphorylated form bound to the granule membrane
      at slightly lower levels of calcium than the native form. The phosphorylated
      annexin I also bound to 20% phosphatidylserine/80% phosphatidylcholine vesicles
      at lower Ca2+ levels than the native form. The inhibitory effect of
      phosphorylation on the granule aggregating activity of annexin I was found to be
      amplified by an unusual mechanism: The phosphorylated form inhibited the activity
      of the unphosphorylated form. The possible importance of the regulation of
      annexin I activity by phosphorylation in exocytosis is discussed.

PMID- 1390777
TI  - Insulin induces the phosphorylation of DNA-binding nuclear proteins including
      lamins in 3T3-F442A.
AB  - Insulin binding to its plasma membrane receptor stimulates a cascade of protein
      kinases and phosphatases which ultimately affects multiple processes in the
      membrane, cytosol, and nucleus of the cell, including transcription of specific
      genes. To gain insight into the relationship between the kinase cascade and the
      mechanism of insulin-induced nuclear events, we have studied the effect of
      insulin on the phosphorylation of DNA-binding nuclear proteins in differentiated
      NIH-3T3-F442A adipocytes. Insulin induced the phosphorylation of seven DNA
      binding proteins: pp34, pp40, pp48, pp62, pp64, pp66, and pp72. The half-maximal
      response was observed at 10-30 min and reached its maximum at 60 min. The insulin
      induced phosphorylation of each of these proteins was dose-dependent with ED50S
      of 2-10 nM. The phosphorylation of pp62, pp64, and pp72 took place on serine
      residues. On the basis of immunoprecipitation and immunoblotting experiments with
      anti-lamin antibodies, we found that the insulin-induced DNA-binding
      phosphoproteins pp62, pp64, pp66, and possibly pp48 were related to lamins A and
      C. The ED50 for insulin-stimulated lamin phosphorylation was approximately 10 nM,
      and phosphorylation was half-maximal at 30 min. The insulin-dependent
      phosphorylation of lamins and other DNA-binding proteins (pp34, pp40, and pp72)
      may play a mediatory role in the long-term effects of insulin.

PMID- 1390778
TI  - Postbinding characterization of five naturally occurring mutations in the human
      insulin receptor gene: impaired insulin-stimulated c-jun expression and thymidine
      incorporation despite normal receptor autophosphorylation.
AB  - Some patients with extreme insulin resistance have mutations in their insulin
      receptor gene. We previously identified five such mutations located in the
      extracellular domain of the insulin receptor (Asn-->Lys15, His-->Arg209, Phe-
      >Val382, Lys-->Glu460, and Asn-->Ser462) and studied the effects of these
      mutations upon posttranslational processing, insulin binding, and tyrosine
      autophosphorylation. We now characterize the ability of these mutant receptors to
      mediate biological actions of insulin in transfected NIH-3T3 fibroblasts. All
      cell lines expressing mutant receptors showed marked impairment in insulin
      stimulated c-jun expression and thymidine incorporation when compared with cells
      expressing wild-type human insulin receptors. The most severe impairment was seen
      in cells expressing the Val382 mutant (a mutation which causes an intrinsic
      defect in receptor autophosphorylation). These cells had insulin responses
      similar to the untransfected cells (used as a negative control). In contrast,
      cells expressing the Lys15 mutant have the ability to achieve a normal level of
      maximal autophosphorylation but require an abnormally high concentration of
      insulin to do so (as the result of decreased insulin binding affinity). These
      cells show a higher basal rate and much lower insulin stimulation of both c-jun
      expression and thymidine incorporation when compared with the cells expressing
      the wild-type human insulin receptors. This pattern is also seen in the cells
      expressing the other mutants with normal autophosphorylation (Arg209, Glu460, and
      Ser462). Although the most severe defects in insulin action are seen with the
      mutation which has an intrinsic defect in receptor autophosphorylation, the
      ability to undergo normal autophosphorylation does not seem to preclude mutations
      from impairing the ability of receptors to mediate some of the actions of
      insulin.

PMID- 1390779
TI  - Isopentenyl-diphosphate isomerase: irreversible inhibition by 3-methyl-3,4
      epoxybutyl diphosphate.
AB  - Isopentenyl-diphosphate:dimethylallyl-diphosphate isomerase (EC 5.3.3.2)
      catalyzes the 1,3-allylic rearrangement of the homoallylic substrate isopentenyl
      diphosphate (IPP) to its allylic isomer, dimethylallyl diphosphate (DMAPP).
      Incubation of yeast IPP isomerase with 3-methyl-3,4-epoxybutyl diphosphate (EIPP)
      resulted in a time-dependent first-order loss of activity characteristic of an
      active-site-directed irreversible process, where k2 = 0.63 +/- 0.10 min-1 and KI
      = 0.37 +/- 0.11 microM. A 1:1 covalent E-I complex was formed upon incubation
      with [1-14C]EIPP. The inhibited enzyme was treated with trypsin to give two
      radioactive fragments, which were purified by reversed-phase HPLC on a C18
      column. The modified amino acid in each fragment was identified as C139 by
      sequencing the radiolabeled peptides. Incubation of IPP isomerase with [2,4,5
      13C3]EIPP gave a 13C-labeled E-I complex. A 1H-13C heteronuclear multiquantum
      correlation spectrum had strong cross-peaks at 1.2/28 and 2.9/48 ppm, which we
      assigned to the labeled methyl group and C(4) methylene, respectively, of the
      inhibitor. In addition, a weak signal at 2.17/42 ppm may be from the C(2)
      methylene. Comparison of these chemical shifts with those of a synthetic adduct
      isolated from treatment of EIPP with cysteine indicates C139 attacks C(4) of EIPP
      to generate a thioether linkage between the enzyme and the inhibitor.

PMID- 1390780
TI  - Mechanism of Agrobacterium beta-glucosidase: kinetic studies.
AB  - The beta-glucosidase from Agrobacterium faecalis (previously Alcaligenes
      faecalis) has been subjected to a detailed kinetic investigation with a range of
      substrates to probe its specificity and mechanism. It has a relatively broad
      specificity for the substrate sugar moiety and exhibits a classical pH dependence
      for its kinetic parameters with three different substrates and an identical pH
      dependence for its inactivation by a mechanism-based inactivator, cyclophellitol.
      Measurement of kcat and Km values for a series of aryl glucoside substrates has
      allowed construction of a Bronsted plot, the concave-downward shape of which is
      consistent with the anticipated two-step mechanism involving a glucosyl-enzyme
      intermediate which is formed and hydrolyzed via oxocarbonium ion-like transition
      states. The slope of the leaving group-dependent portion of the Bronsted plot
      (beta 1g = -0.7) indicates a large degree of bond cleavage at the transition
      state. Secondary deuterium kinetic isotope effects measured for five different
      aryl glucosides are also consistent with this mechanism and further suggest that
      the transition state for formation of the glucosyl-enzyme intermediate, probed
      with the slower substrates for which kH/kD = 1.06, is more SN2-like than that for
      its hydrolysis (for which kH/kD = 1.11). Reasons for this difference are
      proposed, and values of Ki for several ground-state and transition-state analogue
      inhibitors are presented which support the concept of sp2-hybridized transition
      states.

PMID- 1390781
TI  - Inactivation of a beta-glucosidase through the accumulation of a stable 2-deoxy-2
      fluoro-alpha-D-glucopyranosyl-enzyme intermediate: a detailed investigation.
AB  - The inactivation of glycosidases by 2-deoxy-2-fluoroglycosides has been shown
      previously to occur via the accumulation of a covalent 2-deoxy-2-fluoro-alpha-D
      glucopyranosyl enzyme intermediate [Withers, S. G., & Street, I. P. (1988) J. Am.
      Chem. Soc. 110, 8551]. Further characterization of this process with
      Agrobacterium beta-glucosidase is described, and the range of glycosides engaging
      in this behavior is examined. Inactivation is shown to be accompanied by the
      release of a stoichiometric "burst" of aglycon, thereby providing a new class of
      active site titration agents for glycosidases. The rate of inactivation is shown
      to be very strongly dependent on the leaving group ability of the aglycon, the
      slowest inactivator studied (p-nitrophenyl2-deoxy-2-fluoro-beta-D
      glucopyranoside) yielding only partial inactivation due to turnover of the
      intermediate becoming competitive with its formation. Such turnover of the
      intermediate is shown to be greatly accelerated by transglycosylation to a
      suitable glycoside bound in the aglycon site, resulting in the release of a
      disaccharide product which was isolated and characterized. The pH dependences of
      both the formation and the hydrolysis of the 2-deoxy-2-fluoroglycosyl-enzyme
      closely resemble those of each step for normal catalysis, indicating that the
      same catalytic groups are involved in both processes. A model system for the
      partial "steady-state" inactivation observed previously [Withers, S. G., Rupitz,
      K., & Street, I. P. (1988) J. Biol. Chem. 263, 7929] with certain other
      glycosidases was established by incubating the enzyme with an inactivator known
      to undergo relatively rapid transglycosylation in the presence of various
      concentrations of a suitable reactivator.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390782
TI  - Adolescent health--a time for action.

PMID- 1390783
TI  - Keynote address at the Fifth Congress of the International Association for
      Adolescent Health.

PMID- 1390784
TI  - Changing patterns of adolescent sexual behavior: consequences for health and
      development.
AB  - Sexuality is a fundamental quality of human life, important for health,
      happiness, individual development, and indeed for the preservation of the human
      race. During the dynamic period of adolescence in which the passage from
      childhood to maturity takes place, sexuality takes on new dimensions; feelings
      become more intense, relationships become more complex, and the consequences of
      sexual behavior are radically altered. This not only affects the behavior of
      young people but also of those who interact with them, their families and peers,
      and those who work in the health, education, youth, social welfare, and other
      sectors. In the contemporary world the conditions of life for many young people
      have also changed, and with it patterns of sexual behavior. In general, earlier
      puberty, later marriage, a decline in the family leading to less control and more
      autonomy, and intense exposure to sexual stimuli via the mass media and travel
      across cultural boundaries have made pre-marital adolescent sexual activity more
      common. This has added to traditional problems of early marriage, newer problems
      of early pregnancy, childbirth, and induced abortion outside of marriage,
      sexually transmitted diseases, and human immunodeficiency syndrome infection
      leading to acquired immunodeficiency syndrome. But the work of the World Health
      Organization (WHO), along with many others in the field, strongly suggests that
      given appropriate information and services, trust and equity between the sexes,
      young people will behave responsibly and well. In this paper some of the findings
      from methods developed by WHO for research, training, advocacy, and evaluation,
      and findings in relation to patterns and determinants of sexual and reproductive
      health and development will be described, and future directions suggested.

PMID- 1390785
TI  - Positive approaches to education for sexual health with examples from Asia and
      Africa.

PMID- 1390786
TI  - Models for effective prevention.
AB  - The social influence models do provide some optimism for primary prevention
      efforts. Prevention programs appear most effective when 1) the target behavior of
      the intervention has received increasing societal disapproval (such as cigarette
      smoking), 2) multiple years of behavioral health education are planned, and 3)
      community-wide involvement or mass media complement a school-based peer-led
      program (45,46). Short-term programs and those involving alcohol use have had
      less favorable outcomes. Future research in primary prevention should address
      concerns of high-risk groups and high-risk countries, such as lower income
      populations in the United States or countries that have large adolescent homeless
      populations. The utilization of adolescent leaders for program dissemination
      might be particularly critical in these settings. A second major and global
      concern should focus upon alcohol use and alcohol-related problems. In many
      communities adolescent alcohol use is normative and even adult supported. Thus,
      young people are getting quite inconsistent messages on alcohol from their
      schools, from TV, from peers, and from parents. This inconsistency may translate
      into many tragic and avoidable deaths for young people. Clearly, in the area of
      alcohol-related problems, community-wide involvement may be necessary. A third
      direction for prevention research should involve issues of norms, access, and
      enforcement including policy interventions, such as involve the availability of
      cigarette vending machines or the ease of under-age buying or levels of taxation.
      These methods affect adolescents more acutely since their financial resources,
      for the most part, are more limited. These policy level methods also signify to
      adolescents what adults consider appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390787
TI  - Chronic illness and disability in adolescence.

PMID- 1390789
TI  - Adolescents with long-term illness and compliance: a clinician's perspective.

PMID- 1390788
TI  - Youths with chronic illness and disability on their way to social and economic
      participation: a health-care perspective.

PMID- 1390790
TI  - Compliance in adolescents with epilepsy or diabetes.

PMID- 1390791
TI  - Fast food and snack food: beneficial or deleterious.

PMID- 1390792
TI  - Dietary habits, food consumption, and nutrient intake during adolescence.
AB  - Adolescents and young adults adopt eating patterns which may well form the basis
      of their dietary habits for much of their lives. At the same time, this section
      of the population can come under considerable pressure from the world at large,
      to conform to the current trends in fashion, language, behavior, or foods. Recent
      developments in Western dietary practice have tended to leave adolescents
      vulnerable to low intakes of energy and of some nutrients, as snacking accounts
      for an increasing proportion of dietary intake. Achieving a balanced diet is more
      difficult when the most popular and widely available snack foods are high in
      sugar or in fat. Results from major British studies, together with a review of
      data from other developed countries, support the need for more effective dietary
      education for adolescents and for children generally.

PMID- 1390793
TI  - The overall impact of recently developed foods on the dietary habits of
      adolescents.

PMID- 1390794
TI  - Comparison of the self-image of teenagers in Finland, the United States, and
      Germany.
AB  - In this research, the self-image of Finnish adolescents was compared with the
      self-images of American and West German adolescents. Results show that there are
      statistically significant differences between Finnish adolescents and American
      adolescents in five areas. Finnish adolescents are emotionally healthier than
      American adolescents, and their mood is better. American adolescents have higher
      vocational and educational goals than Finnish adolescents, and their adaptation
      skills to immediate environment and their coping skills are better. Differences
      between Finnish and West German adolescents are found in four scales. The
      affective harmony of the psychic structure of Finnish adolescents and their
      object relationships and friendships are better developed than those of West
      German adolescents. West German adolescents have higher vocational and
      educational goals than Finnish adolescents and their coping skills with
      themselves, other people, and their own world are better. Emotional tone (mood)
      is an area where Finnish adolescents scored higher than the American and the West
      German adolescents. Vocational and educational goals and adjustment skills are
      well developed in adolescents from the United States and West Germany.
      Adolescents in these three countries are alike in Impulse Control, Body Image,
      Sexual Attitudes, and Family Relations.

PMID- 1390795
TI  - Evaluation of self-image of overweight teenagers living in Budapest.

PMID- 1390796
TI  - From a fear of getting fat to a desire of becoming thin.

PMID- 1390797
TI  - Atypical eating disorders.
AB  - Some patients with eating disorders have neither anorexia nervosa (A.N.) nor
      bulimia. Cases which do not rigorously meet the DSM-III-R criteria for anorexia
      nervosa or for bulimia are usually defined as "eating disorders N.O.S." Among
      them are patients with pathological characteristics very closely related to the
      above-mentioned categories. Others, however, although affected by an eating
      disorder, present a quite different clinical picture from either A.N. or bulimia.
      In a study of 80 eating disorder cases, only 45 met the strict definition of A.N.
      or bulimia. The other 35 were diagnosed as atypical eating disorders and are the
      focus of this presentation. 29 were classified as Eating Disorders N.O.S. and 6
      as obesity. Co-morbidity, gender and age data, and clinical vignettes are
      presented.

PMID- 1390798
TI  - Treating the distorted body experience of anorexia nervosa patients.

PMID- 1390799
TI  - Suicide prevention in adolescence: an overview of current trends.

PMID- 1390800
TI  - A tentative epidemiologic approach to suicide prevention in adolescence.
AB  - During adolescence (by convention, 10-19 years of age), the global mortality
      rates are relatively low in most countries. Nevertheless, suicidal mortality
      rates are usually second (after all accidents) or third (after accidents and
      homicides), depending on the country. Rates in males are regularly higher than
      those in females. Owing to the universal absence of a systematic recording of
      parasuicide cases, morbidity data are obviously much more difficult to get and to
      analyze properly. Data based on hospital admissions give only approximations.
      Nevertheless, in this age group, parasuicide is expected to be many times more
      frequent in females than in males. Epidemiologic studies on relapses as well as
      parasuicide follow-up are rare. Taking into account the number and heterogeneity
      of known risk factors, suicidal behavior prediction is based on probability
      statistics: valuable only for groups ("high-risk profiles"), never for
      individuals. This is particularly true in adolescence, when so many changes occur
      rapidly. Preventative measures are to be discussed according to their pertinence
      in each of the three classic levels of prevention.

PMID- 1390801
TI  - The outcome of attempted suicide in adolescence.

PMID- 1390802
TI  - Adolescence: the crossroads of violence.
AB  - We sought to distinguish between aggressivity and true violence. Violence is a
      vital force, a life instinct, or, more particularly, a survival instinct.
      Violence is neither good nor bad. Everything depends on the way in which this
      essential instinct is used in the succession of crises that mark the affective
      development of each and every one of us, and, in particular, during the crisis of
      adolescence. The measure of prevention could be based on the elements of pure
      violence and not on established aggressivity. The primary prevention of the
      deviations toward natural violence fits into the framework of the education for
      health. That is only possible if we today prepare future parents and educators of
      the children of tomorrow.

PMID- 1390803
TI  - Young people's perceptions of health and health care--World Health Organization
      (WHO) special session. Adolescents in our society.

PMID- 1390804
TI  - Confederation Senegalaise du Scoutisme (Senegalese Scouting Confederation)
      presentation of the "Xall Yoon" project.

PMID- 1390805
TI  - The socioprofessional rehabilitation of disabled adolescents.

PMID- 1390806
TI  - Turning adolescent medicine inside out (presidential address).

PMID- 1390807
TI  - Adolescents' access to health care.

PMID- 1390808
TI  - The epidemic physicians are leaving to others.

PMID- 1390809
TI  - Gallagher Lecture. Adolescence as a transition period: continuities and
      discontinuities in conduct disorder.

PMID- 1390810
TI  - Self-reported anger in black high school adolescents.
AB  - The purpose of this study was to explore the recognition and expression of anger
      in black high school adolescents. A total of 56 teens, aged 14-19 years,
      responded to questions about their recognition of anger, how and to whom they
      express anger, and to whom they refrain from expressing anger. They also stated
      their opinions about acceptable and unacceptable expressions of anger and its
      relationship to depression or suicide. Data were analyzed using frequency
      tabulations for all questions on the survey instrument. Specific variables of
      age, grade in school, gender, and family composition were analyzed by one-sample
      chi 2 tests (alpha set at 0.05). The study demonstrated 1) all the teens surveyed
      could recognize when they were angry; 2) most teens expressed anger to their
      friends, to their siblings, and to their mothers; 3) younger teens (ages 14-15
      years) when compared to older teens (ages 18-19 years), identified mother as the
      one who made them angry; 4) females were more likely to feel like crying when
      angry; 5) females were more likely to feel like being silent when angry; 6)
      students from one- and two-parent homes did not differ in their expression of
      anger. Implications of this study include the recognition that anger is a
      natural, human emotion. Adolescents need to observe adults who can effectively
      manage behavior associated with anger. Problem solving skills, stress management
      techniques, and role play situations can be utilized as effective tools in the
      recognition and expression of anger in acceptable ways and in attempts at the
      prevention of dysfunctional anger.

PMID- 1390811
TI  - Prevalence of physical and sexual assault in pregnant adolescents.
AB  - Few studies have addressed the prevalence of violence among pregnant adolescents.
      We interviewed 342 pregnant teenagers 17 years of age or younger for a history of
      assault; 9% reported physical assault, 8% sexual assault, and 8% both physical
      and sexual assault. Of those physically abused, 40% had been hit during
      pregnancy. The most common perpetrator of physical assault was a member of their
      family of origin as compared to a mate (46% versus 33%), although a boyfriend or
      spouse was the attacker in 80% of cases in which abuse had increased during
      pregnancy. The face or neck was the most common site of contact. A total of 14%
      reported being hit in the abdomen, one-third of them while pregnant. We conclude
      that a significant proportion of pregnant teenagers have experienced violence and
      therefore should be screened routinely for a history of abuse.

PMID- 1390812
TI  - Violence and its relationship to substance use in adolescent pregnancy.
AB  - We surveyed 342 pregnant adolescents 17 years old and younger for a history of
      physical or sexual assault and substance use to investigate whether victims of
      childhood violence are at increased risk of smoking and using alcohol or drugs. A
      total of 95% of new patients who attended the university's teen pregnancy clinic
      between May 8, 1989, and December 8, 1990, were interviewed. Substance use was
      reported seven times more often in those with a history of combined physical and
      sexual assault, five times more frequently by those who had been sexually
      assaulted, and three times more often in those who had been physically assaulted
      than adolescents without a history of assault. Violence was associated with
      substance use in all ethnic groups although this relationship was modified by
      ethnicity. Among Hispanics, an association was observed between physical assault
      and tobacco use. Sexual and combined physical and sexual assault were strongly
      associated with use of alcohol among blacks. All categories of violence were
      associated with drug use among all ethnic groups. When use of each substance was
      analyzed by the adolescent's relationship to the perpetrator, drug use was most
      strongly associated with assault by a mate, whereas tobacco or alcohol use was
      more often associated with assault by a member of the victim's family of origin.

PMID- 1390813
TI  - Factors related to substance use by pregnant, school-age adolescents.
AB  - This study provides information on substance use among pregnant adolescents, and
      examines social influence, intrapersonal, and environmental factors associated
      with substance use during pregnancy in adolescence. The sample consists of
      premaritally pregnant adolescents (N = 241), who were interviewed as part of a
      longitudinal study of patterns of drug use among pregnant and parenting school
      age adolescents. The findings indicate that, although the sample demonstrated a
      high rate of prepregnancy substance use, a significant drop in use occurred
      during pregnancy. Logistic regression analysis indicated that perceived harm of
      using substances while pregnant, best friend's substance use, boyfriend's
      substance use, and school status were related to substance use during pregnancy,
      even after controlling for the effects of prepregnancy substance use. The
      findings have implications for substance use prevention and intervention programs
      for pregnant and parenting adolescents.

PMID- 1390814
TI  - Substance abuse and syphilis in urban adolescents: a new risk factor for an old
      disease.
AB  - The incidence of syphilis is increasing. To identify the epidemiologic
      characteristics of adolescents with syphilis in an urban adolescent clinic, we
      performed a retrospective review and case-control study of 59 patients with
      syphilis and 111 sex-matched controls seen at our institution between 1985 and
      1988. Only 24% of cases occurred in males, in contrast with 61% in a 1977-1981
      study. Almost one-half (46%) of cases occurred in asymptomatic individuals, and
      only 24% were diagnosed at the initial visit. Patients with syphilis were more
      likely to have a history of substance abuse (odds ratio, 4.94; 95% confidence
      interval, 1.83, 13.3). This study suggests that the epidemiology of syphilis in
      adolescents may be changing. The high percentage of asymptomatic syphilis cases
      underscores the need for a high index of suspicion, particularly in sexually
      active adolescents who abuse drugs.

PMID- 1390815
TI  - Problem drinking among college freshmen.
AB  - Entering college freshmen (n = 308) completed a questionnaire which assessed
      drinking behaviors and identified students at risk for problem drinking as
      defined by the CAGE (focuses on Cutting down on drinking, Annoyance by criticism
      by others about drinking, Guilty feelings about drinking, and the use of an Eye
      opener) questionnaire and Perceived-Benefit-of-Drinking Scale (PBDS). Students
      were 50% male with a mean age of 17.9 years. In the past month, 17% had drunk on
      10 or more occasions, and 18% had binged on 6 or more occasions. CAGE scores of 2
      or greater were obtained by 21% and PBDS scores of 3 or greater by 29%,
      reflecting high risk for problem drinking. High-risk CAGE and PBDS scores were
      associated with frequent drinking and binging. Student reports of parental
      problem drinking were not associated with high risk for problem drinking. Intent
      to join a fraternity or sorority (the Greek system) was associated with frequent
      drinking, binging, and high-risk CAGE and PBDS scores. Approaches to screening
      for problem drinking which emphasize attitudes and beliefs may be useful. The
      Greek system appears to be attractive to high-risk students and should be a focus
      of prevention programming.

PMID- 1390817
TI  - AIDS/HIV knowledge level and perceived chance of having HIV among rural
      adolescents.
AB  - Behaviors that increase the risk of acquired immunodeficiency syndrome (AIDS) and
      human immunodeficiency virus (HIV) among adolescents living in rural areas have
      been reported to be as frequent as those of lower socioeconomic minority youth
      living in large urban areas. Little is known, however, about whether rural
      adolescents possess adequate knowledge upon which to make responsible decisions
      to avoid exposure to HIV. In order to address this deficit, we administered the
      Centers for Disease Control (CDC) 1989 Secondary School Health Risk Survey to 294
      sixth, seventh, and eighth grade students (30.2% sample) from a rural county with
      significant social problems including epidemic sexually transmitted diseases
      STDs, sex-for-drugs, poverty, and drug abuse. The sample was 65% African
      American, 50% female, with a mean age of 12.9 +/- 1.3 years. Although 68%
      reported having received school-based AIDS education, a lower proportion (greater
      than or equal to 10%) the students were found to correctly answer 8 of 17
      AIDS/HIV knowledge questions than those from a national comparison group. The
      mean was 12.8 +/- 3.1 of 17 items answered correct. Lower AIDS/HIV knowledge was
      associated with lower school grade (rho = 0.46, p less than or equal to 0.0001);
      being African-American, Hispanic, or Native American (p less than or equal to
      0.043); and never receiving school-based AIDS/HIV education (p less than or equal
      to 0.0001). Based on multivariate analysis of variance (ANOVA), only school-based
      AIDS/HIV education was a significant predictor (p less than or equal to 0.0001)
      of knowledge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1390816
TI  - Relationship of AIDS-related attitudes to sexual behavior changes in adolescents.
AB  - The impact of the acquired immunodeficiency syndrome (AIDS) epidemic on a group
      of adolescents was investigated by surveying 197 sexually active, predominantly
      African-American, urban high school students. Reported sexual behavior changes
      were evaluated in relation to AIDS-related knowledge and attitudes. Over 50% of
      the students decreased their frequency of sexual activity, increased their condom
      use, and/or decreased their number of partners. These students had significantly
      higher scores on a measure of worry about vulnerability to human immunodeficiency
      virus (HIV) infection than those whose behavior had not changed. AIDS knowledge,
      AIDS beliefs, and AIDS-related anxiety interacted with gender to affect sexual
      behavior change. Male students reporting decreased frequency of sexual activity,
      for example, had more accurate beliefs about AIDS than males reporting no
      decrease. Among female students, however, those reporting decreased frequency had
      less accurate beliefs than those reporting no decrease. These results highlight
      the importance of considering gender and specific sexual behaviors when designing
      AIDS education interventions.

PMID- 1390818
TI  - Partner-specific condom use among adolescent women clients of a family planning
      clinic.
AB  - Because inconsistent condom use could put adolescent women at an increased risk
      for sexually transmitted diseases, it is important to understand when and with
      whom they use condoms. This study examined partner-specific condom use over time
      among adolescent women. The data were from a clinic-based, prospective study of
      308 adolescent women who had at least one sex partner during a 6-month follow-up.
      Their condom use was examined with three types of partners: exclusive,
      nonexclusive primary, and nonexclusive secondary. Predictors of consistent condom
      use (using condoms 100% of the time with a specific partner) were explored in a
      multiple logistic regression analysis. Consistent condom use was more likely to
      occur in shorter relationships (less than 3 months) and with partners who
      preferred condoms for contraception. It was no more likely to occur with
      nonexclusive partners than with exclusive partners, and it was somewhat less
      likely to occur among consistent oral contraceptive users. These findings
      emphasize the importance of educating adolescent women to introduce and maintain
      condom use with all partners.

PMID- 1390820
TI  - Comparison of cytobrush with Cervex-Brush for endocervical cytologic sampling.
AB  - This study was designed to compare the quality of the Papanicolaou (Pap) smear
      and side effects associated with the Ayres spatula/cytobrush combination and the
      Cervex-Brush. We evaluated 165 Pap smears, of which 84 (51%) were
      cytobrush/spatula specimens, and 81 (49%) were from Cervex-Brush specimens. The
      cytobrush/Ayres spatula combination and the Cervex-Brush alone were equally
      successful in detecting squamous cells, however, the cytobrush/Ayres spatula
      combination was significantly better in picking up endocervical cells than the
      Cervex-Brush (p less than 0.01). There were no significant differences between
      the two techniques in degree of bleeding and pain in adolescents. The combination
      of the cytobrush and spatula appears to be superior to the Cervex-Brush alone in
      producing adequate Pap smears.

PMID- 1390819
TI  - Self-efficacy, hedonistic expectancies, and condom-use intentions among inner
      city black adolescent women: a social cognitive approach to AIDS risk behavior.
AB  - The effects on condom-use intentions of an acquired immune deficiency syndrome
      (AIDS) prevention intervention based on social cognitive theory were investigated
      among 19 sexually active black adolescent women recruited from an inner-city
      family planning clinic. The women received the social cognitive intervention
      designed to increase perceived self-efficacy and favorable outcome expectancies
      about the hedonistic consequences of using condoms or one of two control
      interventions: An information-alone intervention designed to increase AIDS
      knowledge or a general health-promotion intervention designed to provide
      information about important health problems other than AIDS. All interventions
      lasted 105 min and involved films and small-group exercises. Participants'
      evaluations did not differ among conditions. As hypothesized, analysis of
      covariance indicated that participants in the social cognitive condition reported
      greater intentions to use condoms than did those in the two control conditions.
      In addition, participants in the social cognitive condition scored higher in
      perceived self-efficacy and favorable hedonistic expectancies--the two
      hypothesized mediators of the intervention effect. Although participants who
      received the information-alone intervention subsequently had greater AIDS
      knowledge than did those in the health promotion condition, they did not express
      greater intentions to use condoms. These results highlight the value of a social
      cognitive approach to AIDS risk behavior: outcome expectancies regarding the
      effects of precautionary practices on sexual enjoyment and perceived self
      efficacy to implement such practices play an important role in decisions about
      condom use.

PMID- 1390821
TI  - Smoking and apolipoproteins in adolescents. The Nino Jesus Group.
AB  - The relation between smoking and blood lipids and apolipoproteins (A1,B100) were
      studied in a group of 1024 12- to 18-year-old school children in the Comunidad de
      Madrid. The percentage of smokers was 19% (17% for girls and 21% for boys). The
      average consumption of cigarettes per day was 7.83 +/- 5.06 in boys and 6.04 +/-
      3.49 in girls (p less than 0.05). As compared with male nonsmokers, male smokers
      showed a higher mean level of low-density lipoprotein (LDL) cholesterol (112
      versus 100 mg/dL, p less than 0.05), a higher LDL cholesterol to HDL-cholesterol
      ratio (2.27 versus 1.94, p less than 0.001), a higher mean level of
      apolipoprotein B100 (59 versus 53 mg/dL, p less than 0.05), and a higher
      apolipoprotein B100 to apolipoprotein A1 ratio (0.45 versus 0.40, p less than
      0.01). Female smokers tended to show the same results, although significant
      differences were only found for LDL cholesterol to HDL cholesterol ratio and
      apolipoprotein B100 to apolipoprotein A1 ratio (1.8 versus 1.59 and 0.41 versus
      0.38 respectively, both p less than 0.05). This work provides new data about the
      effects of smoking on apolipoproteins in adolescents and emphasizes on the need
      for preventive programs.

PMID- 1390822
TI  - Self-reported weight and height in adolescents and their parents.
AB  - Self-reported and measured weight and height were compared in a sample of
      adolescents aged 15 years (109 boys; 95 girls) and their parents (135 fathers;
      190 mothers) recruited from secondary schools in the urban area of Geelong,
      Victoria, Australia. On average the adolescents' self-reported weight and height
      did not differ to a greater extent from the measured values than did that of
      their parents for their own weight and height but differences for individuals
      were much more variable. Self-reported weight was significantly underestimated
      and height over-estimated by both adolescents and parents. Body size had little
      effect on the extent of underestimation of weight and overestimation of height.
      The precision of reporting varied both with age and sex, while reporting bias in
      the parents, but not the adolescents', was influenced by father's occupation
      score. The educational level of the parents, however, had no statistically
      significant effect on reporting bias. The extent to which weight was
      underestimated and height overestimated was no greater than that observed in
      adults and suggests that group means reported for weight and height are likely to
      be as valid a measure of actual weight and height as in adults.

PMID- 1390823
TI  - Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism.

PMID- 1390824
TI  - Assessing hydrophobic regions of the plasma membrane H(+)-ATPase from
      Saccharomyces cerevisiae.
AB  - The hydrophobic, photoactivatable probe TID [3-trifluoromethyl-3-(m
      [125I]iodophenyl)diazirine] was used to label the plasma membrane H(+)-ATPase
      from Saccharomyces cerevisiae. The H(+)-ATPase accounted for 43% of the total
      label associated with plasma membrane protein and incorporated 0.3 mol of
      [125I]TID per mol of 100 kDa polypeptide. The H(+)-ATPase was purified by octyl
      glucoside extraction and glycerol gradient centrifugation, and was cleaved by
      either cyanogen bromide digestion or limited tryptic proteolysis to isolate
      labeled fragments. Cyanogen bromide digestion resulted in numerous labeled
      fragments of mass less than 21 kDa. Seven fragments suitable for microsequence
      analysis were obtained by electrotransfer to poly(vinylidene difluoride)
      membranes. Five different regions of amino-acid sequence were identified,
      including fragments predicted to encompass both membrane-spanning and cytoplasmic
      protein structure domains. Most of the labeling of the cytoplasmic domain was
      concentrated in a region comprising amino acids 347 to 529. This catalytic region
      contains the site of phosphorylation and was previously suggested to be
      hydrophobic in character (Goffeau, A. and De Meis, L. (1990) J. Biol. 265, 15503
      15505). Complementary labeling information was obtained from an analysis of
      limited tryptic fragments enriched for hydrophobic character. Six principal
      labeled fragments, of 29.6, 20.6, 16, 13.1, 11.4 and 9.7 kDa, were obtained.
      These fragments were found to comprise most of the putative transmembrane region
      and a portion of the cytoplasmic region that overlapped with the highly labeled
      active site-containing cyanogen bromide fragment. Overall, the extensive labeling
      of protein structure domains known to lie outside the bilayer suggests that
      [125I]TID labeling patterns cannot be unambiguously interpreted for the purpose
      of discerning membrane-embedded protein structure domains. It is proposed that
      caution should be applied in the interpretation of [125I]TID labeling patterns of
      the yeast plasma membrane H(+)-ATPase and that new and diverse approaches should
      be developed to provide a more definitive topology model.

PMID- 1390825
TI  - Several nongenotoxic carcinogens uncouple mitochondrial oxidative
      phosphorylation.
AB  - A number of plasticizers and lipid-lowering drugs induce peroxisomes and cause
      hepatocellular carcinoma in rodents by mechanisms which remain unknown. In this
      study, seven structurally dissimilar peroxisome proliferating agents were shown
      to uncouple oxidative phosphorylation in isolated rat liver mitochondria. For
      example, perfluorooctanoate (0.5 mM) increased succinate-induced (state 4)
      mitochondrial respiration by over 50% while stimulation of state 3 respiration
      with ADP was minimal (i.e., uncoupling occurred). Interestingly, compounds which
      are potent carcinogens in vivo (e.g., Wy-14,643 and perfluorooctanoate) were more
      powerful uncouplers of oxidative phosphorylation in vitro than weak tumor-causing
      agents (e.g., valproate). Uncoupling also occurred in vivo. Basal rates of oxygen
      uptake in perfused livers from chronically treated rats were increased from 137
      +/- 7 mumol g-1/h in pair-fed controls to 153 +/- 5 mumol g-1/h after 2.5 months
      of feeding Wy-14,643 (0.1% w/v in diet). Concomitantly, rates of urea synthesis
      from ammonia, a process highly dependent on ATP supply, were reduced almost
      completely from 104 +/- 10 mumol g-1/h to 13 +/- 6 mumol g-1/h. Bile flow,
      another energy-dependent process, was also reduced significantly by treatment
      with Wy-14,643 in vivo for 24 h. Taken together, these data indicate that energy
      supply for cellular processes such as urea synthesis and bile flow was disrupted
      in vivo due to uncoupling of oxidative phosphorylation by Wy-14,643. It is
      proposed that peroxisomal proliferators accumulate in the liver where they
      uncouple mitochondrial oxidative phosphorylation and interfere with cellular
      energetics.

PMID- 1390826
TI  - Reactivity patterns for redox reactions of monomer forms of myoglobin, hemocyanin
      and hemerythrin.
AB  - Electron-transfer reactions of myoglobin, hemocyanin and hemerythrin with the
      inorganic complexes [Fe(CN)6]3- (oxidant) and [Co(sep)]2+ (reductant) are
      considered. Rate constants kFe (25 degrees C) have been determined for the
      [Fe(CN)6]3- (410 mV) oxidation of horse deoxyMb, I = 0.100 M (NaCl). From the
      decrease in kFe over the range pH 5.5 to 9.0 a pKa of less than 6.2 is obtained,
      most likely due to the involvement of the heme propionate(s). At the higher pH
      values the rate constant is 1.2 x 10(6) M-1 s-1. Rate constants kCo (25 degrees
      C) for the [Co(sep)]2+ (-260 mV) reduction of metMb are also pH-dependent, pKa =
      8.82, corresponding to acid dissociation of the H2O axially coordinated to the
      Fe(III). The rate constant for the aqua-met form is 2.8 x 10(3) M-1 s-1 at pH
      values less than 7.0. In contrast, no reaction is observed for the deoxy and met
      forms of P. interruptus hemocyanin monomer subunit a with the same two complexes
      (k less than 10(2) M-1 s-1). Comparisons are made with rate constants for
      hemerythrin, also as the monomer, which have been determined previously. Rate
      constants for the reactions of deoxy forms with the neutral small molecules, here
      O2 and H2O2, are also considered. Whereas the reactions of [Fe(CN)6]3- and
      [Co(sep)]2+ are at the protein surface, those of O2 and H2O2 are at the active
      site. Hemocyanin with the more buried (approximately 20 A) active site compared
      with myoglobin (3.8 A) and hemerythrin (6.3 A), does not readily undergo electron
      transfer with reagents at the surface. However, with the small molecules O2 and
      H2O2 penetration of the surrounding peptide occurs, with reaction at the active
      site. Rate constants for the three proteins are now of similar magnitude, and in
      the range (2.3-7.8) x 10(7) M-1 s-1 for O2, and 10.9 to 3600 M-1 s-1 for H2O2.

PMID- 1390827
TI  - The manganese and calcium ions of photosynthetic oxygen evolution.

PMID- 1390828
TI  - Kinetics of transport systems dependent on periplasmic binding proteins.
AB  - Rate equations are derived for a transport model involving a water-soluble
      binding protein outside the plasma membrane. On addition of the substrate, the
      conformation of the binding protein changes; the complex then combines with the
      membrane carrier, transferring the substrate to the carrier site. The free
      binding protein leaves and the carrier shifts inward, releasing the substrate
      inside the cell. Exit follows the reverse path. The predicted behaviour is as
      follows. (i) Uptake does not necessarily conform to Michaelis-Menten kinetics.
      (ii) In both the energized and de-energized states, the maximum rate of exit is
      far lower than that of entry; the asymmetry is determined by the conformational
      change in the binding protein, which is independent of the energy state of the
      system. (iii) Exchange transport is inhibited by external substrate and is
      extremely slow; consequently counter-transport is not expected. (iv) The half
      saturation constant in uptake can differ from the dissociation constant of the
      binding protein. (v) The maximum rate of uptake depends on the intrinsic
      substrate affinity of the membrane carrier relative to that of the binding
      protein. (vi) The maximum rate of uptake and the substrate half-saturation
      constant depend on the concentration of the binding protein.

PMID- 1390829
TI  - Phloretin keto-enol tautomerism and inhibition of glucose transport in human
      erythrocytes (including effects of phloretin on anion transport).
AB  - Under various pH conditions phloretin demonstrates keto-enol tautomerism with a
      pK value of 7.26 +/- 0.06. As Wilbrandt has shown ((1950) Arch. Exp. Pathol.
      Pharmacol. 212, 9-29) phloretin added to erythrocytes inhibits glucose efflux,
      but not glucose influx. At pH 6.5 a Ki value of 0.36 and at pH 9 of 22.7 microM
      was measured; only the ketonic form of phloretin contributes to the inhibition of
      glucose efflux. This was also the case for inhibition of galactose efflux and
      anion exchange. The geometry optimization of a large number of conformations of
      the ketonic and enolic forms of phloretin demonstrates different shapes of the
      molecules. Only the ketonic form shows several overlapping structures with beta-D
      glucopyranose. Considering surplus binding of phloretin under glucose efflux
      conditions as being equivalent to the number of glucose transporters, a number of
      about 200,000 molecules was determined. By two independent methods 210,000 and
      171,000 molecules per cell were calculated. This result is in close agreement
      with the number of glucose transporter sites of the erythrocyte.

PMID- 1390830
TI  - Testing models for transport systems dependent on periplasmic binding proteins.
AB  - A carrier model in which transport across the cytoplasmic membrane is mediated by
      a periplasmic binding protein (Krupka, R.M. (1992) Biochim. Biophys. Acta 1110, 1
      10) is shown to account for many of the properties of these systems: (i)
      Michaelis-Menten kinetics; (ii) seemingly irreversible uptake; (iii) the absence
      of exchange transport and counter-transport; (iv) substrate half-saturation
      constants that in different systems may be lower or higher than the dissociation
      constant of the binding protein; (v) the high concentration of the binding
      protein in the periplasm and its weak association with the membrane component.
      The binding protein appears to function as a valve or rectifier that permits the
      substrate to enter the cell, but blocks exit in both the energized and de
      energized states. The asymmetry depends on both the abruptness and the extent of
      the conformational change in the binding protein. Characteristically, these
      systems build up steep gradients across the membrane, circumstances in which such
      a valve might be important. In agreement with the mechanism, (a) the binding
      protein is missing in members of the same family of transporters that function in
      export of the substrate rather than import; and (b) in Gram-positive organisms,
      which have no periplasmic space, binding proteins function while anchored to the
      cytoplasmic membrane.

PMID- 1390831
TI  - Reaction mechanism and asymmetric orientation of the reconstituted chloroplast
      phosphate translocator.
AB  - Proteoliposomes loaded with varying levels of internal substrates were used in
      bisubstrate initial velocity studies to gain insight into the transport mechanism
      of the reconstituted chloroplast phosphate translocator. The kinetic response to
      trans substrates clearly indicated that the one-to-one exchange mediated by this
      translocator proceeds via a ping-pong type, and excluded a sequential type of
      reaction mechanism. It is also shown that reconstitution of the protein leads to
      an unidirectional orientation of the protein within the liposomes being
      orientated right-side-out with respect to chloroplasts. Different transport
      affinities were observed on either side of the membrane and only the outward
      facing transport site of the translocator is able to bind inhibitors i.e.
      pyridoxal 5'-phosphate (PLP) and 4,4'-diisothiocyanostilbene-2,2'-disulfonate
      (DIDS).

PMID- 1390832
TI  - Hexose-specific inhibition in vitro of human red cell Ca(2+)-ATPase activity.
AB  - In a concentration-dependent manner (5.5-27.5 mmol/l), D-glucose incubated in
      vitro with human erythrocyte membranes at 37 degrees C for 1 h inhibited membrane
      Ca(2+)-ATPase activity by up to 75%. The IC50 was 11 mmol/l. L-Glucose was
      ineffective, as were 3-O-methylglucose, 2-deoxyglucose, sorbitol and myo
      inositol. In contrast, D-fructose decreased Ca(2+)-ATPase activity nearly as
      effectively as D-glucose and mannose and galactose at 11 mmol/l were less than
      50% as effective as D-glucose. Tunicamycin (12 pmol/l), but not 10 mmol/l
      aminoguanidine, progressively antagonized in vitro the D-glucose effect on the
      enzyme. Erythrocyte membrane Ca(2+)-ATPase activity may be regulated by
      glycosylation, rather than nonenzymatic glycation.

PMID- 1390833
TI  - Effects of poly(L-lysine) on the structural and thermotropic properties of
      dipalmitoylphosphatidylglycerol bilayers.
AB  - The effects of poly(L-lysine) on the structural and thermotropic properties of
      dipalmitoylphosphatidylglycerol (DPPG) bilayers were studied with differential
      scanning calorimetry (DSC), X-ray diffraction and freeze-fracture electron
      microscopy. For thermal behavior, in the DPPG/poly(L-lysine) system the main
      transition temperature rises to 45.7 degrees C and the pretransition disappears
      in opposition to pure DPPG vesicles. An additional transition appears
      approximately at 36 degrees C for the DPPG/poly(L-lysine) system after incubation
      at 4 degrees C for two months. The incubated sample gives a X-ray diffraction
      pattern having several additional reflections in the range of 0.2-0.9 nm at 15
      degrees C. These results suggest that even in the presence of poly(L-lysine) the
      DPPG bilayers form the subgel (Lc) phase after the long incubation at a low
      temperature. The X-ray diffraction measurements indicate that the structure of
      the Lc phase for DPPG/poly(L-lysine) system is different from that of pure DPPG
      bilayers. On the other hand, in the gel (L beta') phase, the wide-angle X-ray
      diffraction pattern suggests that the presence of poly(L-lysine) hardly affects
      the packing of hydrocarbon chains in the DPPG bilayers. The small-angle X-ray
      diffraction and freeze-fracture electron microscopy exhibit that the DPPG/poly(L
      lysine) system forms a tightly packed multilamellar structure in which the poly(L
      lysine) is intercalated between the subsequent DPPG bilayers.

PMID- 1390834
TI  - Monensin intercalation in liposomes: effect on cytotoxicities of ricin,
      Pseudomonas exotoxin A and diphtheria toxin in CHO cells.
AB  - Monensin, a carboxylic ionophore was intercalated in liposomes (liposomal
      monensin) and its effect on cytotoxicities of ricin, Pseudomonas exotoxin A and
      diphtheria toxin in CHO cells was studied. Intercalation of monensin in liposomal
      bilayer is found to have no effect on its stability and interaction with cells.
      Liposomal monensin (1 nM) substantially enhance the cytotoxicities of ricin (62
      fold) and Pseudomonas exotoxin A (11.5-fold) while it has no effect on diphtheria
      toxin. This observed effect is highly dependent on the liposomal lipid
      composition. The potentiating ability of monensin (1 nM) in neutral vesicles is
      significantly higher (2.2-fold) as compared to negatively charges vesicles. This
      ability is drastically reduced by incorporation of stearylamine in liposomes and
      is found to be dependent on the density of stearylamine as well as on the
      concentration of serum in the medium. Monensin in liposomes containing 24 mol%
      stearylamine has a very marginal effect on the cytotoxicity of ricin (7.5-fold)
      which is further reduced (1.5-fold) in the presence of 20% serum. The uptake of
      125I-gelonin from neutral vesicles is significantly higher (approximately 2.0
      fold) than that from the negative vesicles. The uptake from positive vesicles is
      highly dependent on the concentration of stearylamine. The reduction in the lag
      period (30 min) of ricin action by monensin in neutral and negative vesicle is
      comparable with free monensin. However, monensin in positive vesicle has no
      effect on it. These studies have suggested that liposomes could be used as a
      delivery vehicle for monensin for selective elimination of tumor cells in
      combination with hybrid toxins.

PMID- 1390835
TI  - Lipid mixing is mediated by the hydrophobic surfactant protein SP-B but not by SP
      C.
AB  - Pulmonary surfactant contains two families of hydrophobic proteins, SP-B and SP
      C. Both proteins are thought to promote the formation of the phospholipid
      monolayer at the air/fluid interface of the lung. The excimer/monomer ratio of
      pyrene-labeled PC fluorescence intensities was used to investigate the capacity
      of the hydrophobic surfactant proteins, SP-B and SP-C, to induce lipid mixing
      between protein-containing small unilamellar vesicles and pyrene-PC-labeled small
      unilamellar vesicles. At 37 degrees C SP-B induced lipid mixing between protein
      containing vesicles and pyrene-PC-labeled vesicles. In the presence of negatively
      charged phospholipids (PG or PI) the SP-B-induced lipid mixing was enhanced, and
      dependent on the presence of (divalent) cations. The extent of lipid mixing was
      maximal at a protein concentration of 0.2 mol%. SP-C was not capable of inducing
      lipid mixing at 37 degrees C not even at protein concentrations of 1 mol%. The SP
      B-induced lipid mixing may occur during the Ca(2+)-dependent transformation of
      lamellar bodies into tubular myelin and the subsequent formation of the
      phospholipid monolayer.

PMID- 1390836
TI  - Nucleoside transport-deficient mutants of PK-15 pig kidney cell line.
AB  - Previous studies indicated that PK-15 pig kidney cells express solely a
      nitrobenzylthioinosine-sensitive, equilibrative nucleoside transporter. In the
      present study, PK-15 cells were mutagenized by treatment with ICR-170 and
      nucleoside transport-deficient mutants selected in a single step in growth medium
      containing tubercidin and cytosine arabinoside at a frequency of about 2 x 10(6).
      The mutants were simultaneously at least 100-times more resistant to tubercidin,
      cytosine arabinoside and 5-fluorodeoxyuridine than the wild-type parent cells.
      The mutants failed to transport thymidine and uridine and had lost all high
      affinity nitrobenzylthioinosine binding sites. Residual low level uptake of
      thymidine by the mutants was shown to be due to nonmediated permeation (passive
      diffusion), which explains the sensitivity of the mutants to growth inhibition by
      high concentrations of the nucleoside drugs. Passive diffusion of thymidine at a
      concentration of 16 microM was not rapid enough to support the growth of
      nucleoside transport-deficient mutant cells that had been made thymidine
      dependent by treatment with methotrexate, whereas wild-type cells grew normally
      under these conditions. The nucleoside transport-deficient mutants exhibited
      about the same growth rate and plating efficiency (60-80%) as wild-type cells,
      but formed larger colonies than wild-type cells because of a more extensive
      spread of the cells on the surface of culture dishes. PK-15 cells adhere very
      strongly to the surface of culture dishes and have been transformed with high
      efficiency with plasmid DNA either via lipofection or electroporation.

PMID- 1390837
TI  - Enrichment of saturated fatty acid containing phospholipids in sheep brain
      serotonin receptor preparations: use of microwave irradiation for rapid
      transesterification of phospholipids.
AB  - During enrichment of the 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)
      binding serotonin 5-HT1A receptors from sheep brain gray matter (membrane
      isolation, detergent solubilization and reconstitution into vesicles) a
      consistent and striking increase in the composition of saturated fatty acids was
      observed in phospholipids which were coisolated with the receptors. A rapid
      procedure has been developed for the methylation of free and phospholipid linked
      fatty acids which were thus analyzed by gas chromatography-mass spectrometry
      (GC/MS). Esterification of free fatty acids and transesterification of
      phospholipid linked fatty acids were achieved with 14% boron trifluoride in
      methanol (BF3-CH3OH) in 20 s and 50 s, respectively, under low power microwave
      irradiation (60 W) with a post-reaction cooling of less than 5 min. This is in
      contrast to the conventional method of heating in a boiling water bath for 10-15
      min with BF3-CH3OH which is inevitably preceded by time-consuming and
      inconvenient clamping of vials and followed by cooling for 10 min before the
      vials can be safely opened. Analysis of fatty acid profiles in
      phosphatidylethanolamine (PE) and phosphatidylcholine (PC) from egg yolk,
      phosphatidylinositol (PI) from bovine liver and phosphatidylserine (PS) from
      bovine brain by both techniques showed comparable results. During detergent
      solubilization of sheep brain gray matter, the overall proportion of saturated
      fatty acids in PE (major lipid), PI, PC (major lipid) and PS increased from 50
      60% in sheep brain phospholipids to 70-75% in 1.5% CHAPS solubilized,
      reconstituted and biologically active serotonin 5-HT1A preparations. In sharp
      contrast, the proportions of saturated fatty acids in 1.5% Triton X-100
      solubilized PE (48.1%) (major lipid), PI (63.6%), PC (60.6%) (major lipid) and PS
      (62.2%) were not significantly different from those in the original sheep brain
      membranes. Strikingly, this was coupled with the occurrence of very low levels of
      5-HT1A receptor activity in the Triton X-100 solubilized preparations. The
      abundance of 5-HT1A sites in the enriched vesicles obtained only from the CHAPS
      solubilized preparations was further confirmed by specific radiolabeling of a 58
      kDa polypeptide by the 5-HT1A specific ligand p-aminophenylethyl-m
      trifluoromethylphenylpiparazine (PAPP) which was coupled to a 125I-labeled,
      photoreactive, heterobifunctional cross-linker, sulfosuccinimidyl-2-(p
      azidosalicylamido)ethyl-1,3'-dithiopropiona te (SASD). Thus CHAPS-solubilized 5
      HT1A receptor preparations are depleted in the more rigid lipids such as
      sphingolipids and cholesterol, (Banerjee et al. (1990) Biochim. Biophys. Acta
      1044, 305-314), but are enriched in vesicle-stabilizing, phospholipid-linked
      saturated fatty acids which in turn probably stabilize the heptahelical, membrane
      bound 5-HT1A receptor.

PMID- 1390838
TI  - Inhibition of anion transport in the human red blood cell membrane with para- and
      meta-methoxyphenylglyoxal.
AB  - The positional isomers para-methoxyphenylglyoxal and meta-methoxyphenylglyoxal
      were newly synthesized and found to be potent inhibitors of sulfate exchange in
      the red blood cell membrane. The rate of inactivation of the transport system
      with both reagents obeys pseudo-first-order kinetics and increases with
      increasing pH and reagent concentration. The degree of inhibition of the
      transport system with the meta-isomer exceeds the inhibition caused by the para
      isomer. At 2 mM 3-methoxyphenylglyoxal (3-MOPG) and 37 degrees C the half
      lifetime of the anion transporter is 5.4 min at pH 8.0. Under the same
      experimental conditions the half-lifetime of the transporter at 2 mM 4
      methoxyphenylglyoxal (4-MOPG) is found to be 24.7 min. The binding site of these
      reagents is found to be the same as binding site of the reversibly acting
      phenylglyoxal derivative 4-hydroxy-3-nitrophenylglyoxal (HNPG). Chloride ions are
      able to protect the transporter against inhibition with both reagents. Anion
      transport inhibitors like 4,4'-dinitrostilbene-2,2'-disulfonate (DNDS) and
      flufenemate, which are known to act on band 3 protein, are able to interact with
      the binding of the newly synthesised reagents. Phloretin and phloridzin show no
      interaction.

PMID- 1390839
TI  - Liposome shrinkage and swelling under osmotic-diffusional stress: evaluation of
      kinetic parameters from spectrophotometric measurements.
AB  - Analyses of spectrophotometric measurements of shrinkage and swelling of
      liposomes under osmotic-diffusional stress tacitly assume an 'empirical' inverse
      relationship between the absorbance (A) and the liposomal volume (v). In this
      paper, we have proposed an alternate more explicit relationship: A = EcL e -
      alpha Lv/1-Lv where L is liposomal concentration, Ec the extinction coefficient
      and alpha a dimensionless parameter. The exponential term, in essence, defines
      the partitioning of aqueous volume into intra- and extra-liposomal compartments.
      Experimental data obtained with glycerol as model compound are used to test the
      validity and internal consistency of the proposed formalism.

PMID- 1390840
TI  - Kinetics of melittin induced pore formation in the membrane of lipid vesicles.
AB  - We have investigated the permeabilization of POPC unilamellar vesicle bilayers
      upon the addition of melittin. This process was measured in an early time range
      of a few minutes by means of monitoring the release of an entrapped marker, the
      self-quenching fluorescent dye carboxyfluorescein. Pore formation is indicated by
      an apparent 'all-or-none' efflux out of individual vesicles and a higher than
      linear dependence on melittin concentration. Applying a recently developed
      evaluation procedure, the data are readily converted into the gross number of
      pores per vesicle formed within the elapsed measuring time t. The results can be
      generally described in terms of a fast initial rate of pore formation that slows
      down to a much lower value after a period of about 1 to 2 minutes, following a
      single exponential time course. The three rate parameters involved are shown to
      be power functions of the concentration of melittin that is actually associated
      with the vesicle membrane. These findings are in excellent quantitative agreement
      with a proposed scheme of reaction steps where the formation of lipid associated
      peptide dimers becomes rate determining once an initial fast deposit is
      exhausted.

PMID- 1390841
TI  - Dual specificity of sterol-mediated glycoalkaloid induced membrane disruption.
AB  - In this study the effects of the glycoalkaloids alpha-solanine, alpha-chaconine,
      alpha-tomatine and the aglycone solanidine on model membranes composed of PC in
      the absence and presence of sterols have been analysed via permeability
      measurements and different biophysical methods. The main result is that
      glycoalkaloids are able to interact strongly with sterol containing membranes
      thereby causing membrane disruption in a way which is specific for the type of
      glycoalkaloid and sterol. For this dual specificity both the sugar moiety of the
      glycoalkaloid and the side-chain of the sterol on position 24 turned out to be of
      major importance for the membrane disrupting activity. The order of potency of
      the glycoalkaloids was alpha-tomatine > alpha-chaconine > alpha-solanine. The
      plant sterols beta-sitosterol and fucosterol showed higher affinity for
      glycoalkaloids as compared to cholesterol and ergosterol. The mode of action of
      the glycoalkaloids is proposed to consist of three main steps: (1) Insertion of
      the aglycone part in the bilayer. (2) Complex formation of the glycoalkaloid with
      the sterols present. (3) Rearrangement of the membrane caused by the formation of
      a network of sterol-glycoalkaloid complexes resulting in a transient disruption
      of the bilayer during which leakage occurs.

PMID- 1390843
TI  - Labelling of liposomes with intercalating perylene fluorescent dyes.
AB  - The high fluorescent potential and the exceptional photostability of lipophilic
      derivatives of perylene-3,4:9,10-bis(dicarboximides) are utilized for the
      fluorescence-labelling of liposomes. The preparation of the liposomes is effected
      by supersonic starting from a lipid mixture consisting of the matrix lipids soy
      lecithin, cholesterol, alpha-tocopherol and the perylene dyes. From a multitude
      of perylene derivatives investigated only those are optimally incorporated into
      the bilayer membrane of unilamellar liposomes which are substituted at both
      nitrogen atoms by one or two linear hydrocarbon groups. In order to attain an
      optimal fluorescent quantum yield, about 200 to 300 dye molecules can be
      incorporated per liposome. The liposomes thus obtained have a diameter of about
      70 to 80 nm, are homogeneous and may be stored for more than seven months.
      Neither the fluorescent properties nor the stability of these liposomes are
      influenced by the additional incorporation of various ara C-derivatives and
      lipophilic anchor groups which subsequently enable the coupling of antibodies to
      the liposomes. As the water-insoluble perylene dyes are incorporated into the
      bilayer membrane, the aqueous inner volume of the liposomes remains available for
      a further utilization.

PMID- 1390842
TI  - Separation and inhibitor specificity of a second unidirectional efflux route for
      methotrexate in L1210 cells.
AB  - L1210 cells mediate the unidirectional and energy-dependent efflux of
      methotrexate. Efflux occurs primarily via a system which has a high sensitivity
      to prostaglandin A1, vincristine, reserpine, verapamil, and bromosulfophthalein,
      but evidence has also been obtained for a second efflux component with a lower
      response to these inhibitors. Pretreatment of L1210 cells with low concentrations
      of vincristine reduces methotrexate efflux by three fold and uncovers a second
      efflux component with an inhibitor specificity which is distinctly different from
      the primary efflux route. Vincristine treatment increased by 8-20-fold the
      concentration required for half-maximal efflux inhibition by prostaglandin A1,
      reserpine, bromosulfophthalein, and verapamil but had no effect on inhibition by
      probenecid, quinidine, or carbonylcyanide m-chlorophenylhydrazone. A selective
      block in the primary efflux system and retention of the second component was also
      achieved in cells exposed to low concentrations of prostaglandin A1 or
      bromosulfophthalein. These results support prior conclusions that L1210 cells
      contain both a primary and secondary unidirectional efflux route for
      methotrexate. The second system has been difficult to detect and quantitate since
      it comprises only 25% of total unidirectional efflux and shows a relatively low
      response to various efflux inhibitors.

PMID- 1390844
TI  - Dextran sulfate inhibits fusion of influenza virus and cells expressing influenza
      hemagglutinin with red blood cells.
AB  - The influence of dextran sulfate with molecular weights of 500,000 and 8000 on
      binding and fusion of influenza virus (X31 strain) and of cells expressing
      influenza hemagglutinin (GP4F) with red blood cells (RBC) was investigated by
      spectrofluorimetry using virus and RBC labeled with the fluorescent dye octadecyl
      rhodamine B (R18). There was no significant inhibition of binding of virus and
      GP4F cells to red blood cells by dextran sulfate, but the polymer strongly
      inhibited the low pH induced fusion. Virus-RBC fusion was completely blocked by
      the high molecular weight dextran sulfate at concentrations as low as 0.5 mg/ml.
      Inhibition of RBC-GP4F cell fusion by dextran sulfate in the same concentration
      range was not as pronounced but the effect was potentiated by Ca2+. The polymer
      was only inhibitory when added at early steps of the fusion reaction, but the pH
      induced conformational change of the hemagglutinin was not affected by dextran
      sulfate as measured by its susceptibility to proteolytic digestion. Removal of
      dextran sulfate after low pH-requiring steps allowed the system to fuse at
      neutral pH indicating that the inhibitory effect requires the continuous presence
      of dextran sulfate during the fusion reaction.

PMID- 1390846
TI  - Archaebacterial lipid models: highly salt-tolerant membranes from 1,2
      diphytanylglycero-3-phosphocholine.
AB  - 1,2-Di(3RS,7R,11R-phytanyl)-sn-glycero-3-phosphocholine and its glycerol epimers
      were synthesized as model lipids of archaebacterial halophiles. These
      amphiphiles, upon sonication of aqueous suspensions, gave rise to small
      unilamellar vesicles (SUV) of 300-800 A in diameter and about 80 A in the
      membrane thickness. The liposomes were very stable for at least a month even in a
      highly concentrated suspension or 5 M aqueous NaCl. The vesicles could retain Na+
      and Cl- ions as well as 5(6)-carboxyfluorescein in the aqueous interior at
      temperature as high as 70 degrees C. The liposomes of ordinary diester lipids
      such as 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and egg-yolk lecithin were
      less stable and more permeable than those of the diphytanyl lipids.

PMID- 1390845
TI  - Characterization of the TRH-induced activation of Na+/H(+)-exchange in pituitary
      GH4C1 cells.
AB  - In the present study in GH4C1 cells, the dependence of TRH-induced activation of
      Na+/H(+)-exchange on extracellular Na+ and Ca2+ was examined. Furthermore, the
      effects of both extracellular and intracellular H+ on Na+/H(+)-exchange were
      investigated. The buffering capacity was 63 +/- 11.8 mM (pH unit)-1 at basal
      intracellular pH (pHi) of 7.02 +/- 0.02. The initial rate of alkalinization in
      cells acidified with nigericin increased with increasing concentrations of
      extracellular Na+ according to simple Michaelis-Menten kinetics. The apparent Km
      value for Na+ was 53 +/- 17.5 mM and the Vmax value was 28 +/- 4.5 mM H+/min.
      Addition of Na+ together with TRH increased Vmax to 56 +/- 6.4 mM H+/min (P <
      0.05), while no difference was observed in Km. Decreasing extracellular pH (pHo)
      decreased the rate of alkalinization of acid-loaded cells, despite a large inward
      Na+ gradient. Furthermore, a decrease in pHi was necessary to obtain activation
      of Na+/H+ exchange. At pHi-values close to basal pHi no activation of Na+/H(+)
      exchange was obtained. In addition, the results showed that extracellular Ca2+
      was necessary for TRH-induced activation of Na+/H+ exchange. Blocking influx of
      extracellular Ca2+ with Ni2+ abolished the effect of TRH, suggesting that the TRH
      induced activation of Na+/H(+)-exchange in GH4C1 cells is dependent on influx of
      extracellular Ca2+.

PMID- 1390847
TI  - Nuclear magnetic relaxation dispersion and 31P-NMR studies of the effect of
      covalent modification of membrane surfaces with poly(ethylene glycol).
AB  - Covalent attachment of methoxypoly(ethylene glycol) (MPEG) 5000 to the surface of
      unilamellar liposomes composed of egg phosphatidylcholine and
      dioleoylphosphatidylethanolamine (DOPE) (8:2) containing paramagnetic chelates,
      either entrapped within the interior volume of the liposomes, or associated with
      the membrane surface, had no effect upon the measured spin-lattice relaxation
      rates (1/T1) for water in these systems. 31P-NMR studies indicate no
      destabilization of dioleoylphosphatidylcholine (DOPC)/(DOPE) (1:1) vesicles
      following attachment of MPEG. However, in DOPC/DOPE (1:3) mixtures, covalent
      modification with MPEG results in a destabilization of multilamellar vesicles
      into smaller vesicular structures. These results indicate that covalent
      attachment of poly(ethylene glycol) to liposomal magnetic resonance agents may
      prove a useful method for increasing their utility as vascular MR agents by
      extending their lifetime in the circulation, without decreasing the relaxivity of
      paramagnetic species associated with the liposome, but that the presence of PEG
      covalently attached to the membrane surface may modify the polymorphic phase
      behavior of the lipid system to which it is covalently linked.

PMID- 1390848
TI  - Activation of the Na+/K+/Cl- cotransport system by reorganization of the actin
      filaments in Ehrlich ascites tumor cells.
AB  - Reorganization (disassembly) of the actin filaments in Ehrlich ascites tumor
      cells, either by hypotonic treatment in the presence of Ca2+ or by addition of
      cytochalasin B, results in activation of the Na+/K+/Cl- cotransport system.
      However, other regulatory processes, some of which may be dependent on an intact
      filament system, are responsible for the activation of the Na+/K+/Cl- cotransport
      system after cell shrinkage.

PMID- 1390849
TI  - The fusion of artificial lipid membranes induced by the synthetic arenavirus
      'fusion peptide'.
AB  - The fusing activity of the synthetic 23 amino-acid fragment (fusion peptide, FP)
      of the fusion protein of the Lassa arenavirus membrane was tested in a model
      liposomal system. The resonance energy transfer between two fluorescent
      phospholipid probes was monitored in order to detect dioleoylphosphatidylcholine
      liposome fusion induced by the peptide. Fusion rates were compared at different
      pH values, ionic strength and calcium concentrations. FP demonstrated fusing
      activity at pH 4.5-5.5, indicating that the protonated form of the FP is the
      active one. A transmembrane proton-gradient induced by acidification was not
      relevant to the fusion process, since its elimination with nigericin did not
      affect the FP-mediated fusion. Both Ca2+ (8 mM) and the increase of the ionic
      strength (1 M NaCl) inhibited liposome fusion. The efficacy of liposome fusion
      depended also on the lipid-to-lipid ratio. Non-linear dependence was observed at
      a saturation ratio of 10 mol lipid per mol peptide. A model of 'side insertion'
      is suggested, describing FP interaction with the membrane.

PMID- 1390851
TI  - Formation of non-bilayer structures induced by M13 coat protein depends on the
      conformation of the protein.
AB  - A comparison is made of the interaction of the coat protein of bacteriophage M13
      in a predominant alpha-helix conformation and in a predominant beta-sheet
      conformation. To perform a systematic study of the interaction between the
      protein in these two different forms of the surrounding lipid matrix, NMR spectra
      of 2H-nuclei of specific labelled phospholipid systems are measured. In addition
      31P-NMR is employed to provide information about the morphological structure
      adopted by the reconstituted lipid/protein systems. From the 2H-NMR studies on
      specific headgroup and chain deuterium labelled phospholipids it is found that
      the protein in the predominant beta-sheet conformation causes a fraction of
      lipids to be trapped. By combining the results from the headgroup and acyl chains
      of the phospholipids, it is concluded that the trapped lipids are arranged in a
      non-bilayer structure, probably caused by a misfitting of the hydrophobic core of
      the protein and the membrane bilayer. The protein in the predominant alpha-helix
      conformation perfectly fits in the lipid bilayer and has only minor influences on
      the surrounding lipid matrix. A new model is proposed to explain the presence of
      the trapped lipids in the lipid/protein systems.

PMID- 1390850
TI  - Polarity of transport of 2-deoxy-D-glucose and D-glucose by cultured renal
      epithelia (LLC-PK1).
AB  - At least two types of glucose transporter exist in cultured renal epithelial
      cells, a Na(+)-glucose cotransporter (SGLT), capable of interacting with D
      glucose but not 2-deoxy-D-glucose (2dglc) and a facilitated transporter (GLUT)
      capable of interacting with both D-glucose and 2dglc. In order to examine the
      polarity of transport in cultured renal epithelia, 2dglc and D-glucose uptakes
      were measured in confluent cultures of LLC-PK1 cells grown on collagen-coated
      filters that permitted access of medium to both sides of the monolayer. The rates
      of basolateral uptake of both 1 mM glucose (Km 3.6 mM) and 1 mM 2dglc (Km 1.5 mM)
      were greater than apical uptake rates and the (apical-to
      basolateral)/(basolateral-to-apical) flux ratio was high for glucose (9.4) and
      low for 2dglc (0.8), thus, confirming the lack of interaction of 2dglc with the
      apical SGLT. Specific glucose transport inhibitor studies using phlorizin,
      phloretin and cytochalasin B confirmed the polarised distribution of SGLT and
      GLUT in LLC-PK1 cells. Basolateral sugar uptake could be altered by addition of
      insulin (1 mU/ml) which increased 2dglc uptake by 72% and glucose uptake by 50%
      and by addition of 20 mM glucose to the medium during cell culture which
      decreased 2dglc uptake capacity at confluence by 30%. During growth to
      confluence, 2dglc uptake increased to a maximum, then decreased at the time of
      confluence, coincident with a rise in uptake capacity for alpha-methyl-D
      glucoside, a hexose that interacts only with the apical SGLT. It was concluded
      that the non-metabolisable sugar 2dglc was a useful, specific probe for GLUT in
      LLC-PK1 cells and that GLUT was localised at the basolateral membrane after
      confluence.

PMID- 1390853
TI  - Osmotic swelling and membrane conductances in A6 cells.
AB  - Hyposmotic basolateral perturbations (-30 mosmol/kg) in cultured renal layers
      (A6) increased basolateral membrane conductance more than 2-fold within 10 min;
      the increase was partly due to upregulation of K+ conductance, but other
      conductive pathways were also activated. The raise in apical membrane amiloride
      sensitive Na+ conductance was less pronounced; it appears to be due to secondary
      effects.

PMID- 1390852
TI  - Alcohols dehydrate lipid membranes: an infrared study on hydrogen bonding.
AB  - The effects of alcohols (methanol, ethanol, and n-butanol) on the hydrogen
      bonding of dipalmitoylphosphatidylcholine (DPPC) were studied by Fourier
      transform infrared spectroscopy (FTIR) in water-in-oil (carbon tetrachloride)
      reversed micelles. The bound O-H stretching mode of water, bonded to DPPC,
      appeared as a broad band at around 3400 cm-1. The O-H bending mode of this
      complex appeared as a weak broad band at 1644 cm-1. No free O-H signal was
      observed. When alcohols were added, a part of DPPC-bound water was replaced by
      the alcohols. The released 'free' water appeared at 3680 cm-1. This free O-H
      stretching band represents water-alcohol complex. A new broad band of O-H
      stretching appeared at 3235 cm-1, which represents the alcohol molecules bound to
      the phosphate moiety of DPPC. When the alcohol concentration was increased, the
      intensities of the free O-H stretching and bending bands increased. The P = O-
      antisymmetric stretching band at 1238 cm-1 became broader and shifted to lower
      frequencies. This means that alcohols interacted with the phosphate moiety and
      replaced the bound water. In the deconvoluted spectra of the C = O stretching
      mode, the ratio between the free sn-2 and the hydrogen-bonded sn-2 bands
      increased; a part of the bound water at the sn-2 carbon in the glycerol skeleton
      is also released and the free sn-2 signal increased. From the change in the
      intensity of the P = O- stretching band, the partition coefficients of alcohols
      between the phosphate region of DPPC and water were estimated: methanol 7.8,
      ethanol 16.7 at 22.0 degrees C in mole fraction bases. In molality, these values
      translates into methanol 0.21 and ethanol 0.45. These results indicate that short
      chain alcohols interact with lipid membranes at the phosphate moiety at the
      hydrophilic head, weaken the membrane-water interaction, and destabilize
      membranes.

PMID- 1390855
TI  - Effects of membrane lipids and -proteins and cytoskeletal proteins on the
      kinetics of cholesterol exchange between high density lipoprotein and human red
      blood cells, ghosts and microvesicles.
AB  - To better understand the effects of plasma membrane lipids and proteins and the
      cytoskeleton on the kinetics of cellular cholesterol efflux, the effects of (1),
      selectively depleting either sphingomyelin (SM) or phosphatidylcholine (PC); (2),
      cross-linking the cytoskeleton, and (3), removing certain cytoskeletal and
      integral membrane proteins on radiolabelled cholesterol efflux from red blood
      cells (RBC) have been studied. When RBC were treated with either phospholipase A2
      or sphingomyelinase C to hydrolyze either 30-40% of the PC or 40-50% of the SM,
      respectively, the halftimes (t1/2) for cholesterol efflux to excess HDL3 were not
      significantly altered, with the values being 4.4 +/- 0.8 h or 3.7 +/- 0.4 h,
      respectively, compared to 4.6 +/- 0.6 h for control RBC. To investigate the
      effects of the cytoskeleton on the rate of free cholesterol (FC) desorption from
      the plasma membrane, the cytoskeletal proteins were cross-linked by either heat
      treatment or exposure to diamide and cholesterol efflux from ghosts of these
      cells was measured. Cross-linking the cytoskeletal proteins by diamide treatment
      resulted in no significant change in t1/2 for treated (3.6 +/- 0.6 h) compared to
      control (4.2 +/- 0.4 h) ghosts: this suggests that the cytoskeleton does not play
      a large role in modulating cholesterol efflux. To investigate the effects of
      membrane proteins on cholesterol efflux, RBC microvesicles, containing mainly
      band 3 and 4 proteins and little of the cytoskeletal proteins, such as spectrin
      (bands 1,2) or actin (band 5), were obtained by incubation with the ionophore
      A23187. With excess HDL3 present, microvesicles exhibited a t1/2 of 4.2 +/- 1.9 h
      (compared to the t1/2 of 4.2 +/- 0.4 h for control ghosts). The results described
      in this paper suggest that neither changing the SM/PC ratio in the membrane nor
      cross-linking the cytoskeletal proteins nor removing the cytoskeleton changes the
      t1/2 for cholesterol efflux to excess HDL3. Presumably, the cholesterol
      phospholipid interactions are insensitive to these perturbations in membrane
      structure.

PMID- 1390854
TI  - Evidence that the scavenger receptor is not involved in the uptake of negatively
      charged liposomes by cells.
AB  - Scavenger receptors have a broad ligand specificity, ranging from modified low
      density lipoproteins to a variety of high-molecular-weight poly-anions. A recent
      report by Nishikawa et al. (J. Biol. Chem. (1990) 265, 5226-5231) suggested that
      this receptor is also involved in the binding and endocytosis of liposomes
      containing negatively charged phospholipids. The mechanism by which liposomes are
      taken up by cells is of interest because liposomes are promising versatile
      carriers for macromolecules and drugs both in vitro and in vivo. In this report,
      we re-examine the role of the scavenger receptor in the uptake of liposomes using
      both Chinese hamster ovary cells transfected with the type I or type II bovine
      scavenger receptor, and smooth muscle cells induced to increase scavenger
      receptor expression by phorbol ester treatment. Expression of both types of
      scavenger receptors by Chinese hamster ovary cells induced an increase in the
      uptake of chemically modified low-density lipoproteins, but not the uptake of
      negatively charged liposomes. In smooth muscle cells treated with phorbol ester,
      scavenger receptor expression was upregulated and the uptake of chemically
      modified low-density lipoproteins was enhanced dramatically, but there was no
      effect on the uptake of negatively charged liposomes. We conclude that the
      existing evidence does not support the suggestion that the scavenger receptor is
      involved in the uptake of anionic liposomes by cells.

PMID- 1390856
TI  - Na+/K+/Cl- cotransport in resealed ghosts from erythrocytes of the Milan
      hypertensive rats.
AB  - The erythrocytes (RBC) of the Milan hypertensive rats (MHS) have a smaller volume
      and faster Na+/K+/Cl- cotransport than RBC from normotensive controls (MNS). The
      difference in Na+/K+/Cl- cotransport is no longer present in inside-out Vesicles
      (IOV) of RBC membrane. To differentiate between cytoplasmic or membrane skeleton
      abnormalities as possible causes of these differences. Resealed ghosts (RG) were
      used to measure ion transport systems. The following results have been obtained:
      (1) RG from MHS have a smaller volume than MNS (mean +/- S.E. 20.7 +/- 0.45 vs.
      22.09 +/- 0.42 fl, P < 0.05). (2) RG showed a bumetanide-sensitive Na efflux that
      retains the characteristics of the Na+/K+/Cl- cotransport of the original RBC: it
      is K(+)- and Cl(-)-sensitive and dependent on the intracellular Na+
      concentration. (3) The Na+/K+/Cl- cotransport was faster in RG from MHS than in
      those from MNS (mean +/- S.E. 0.095 +/- 0.01 vs. 0.066 +/- 0.01 rate constant h
      1, P < 0.01). These results, together with those of IOV, support the hypothesis
      that an abnormality in the membrane skeletal proteins may play a role in the
      different Na+/K+/Cl- cotransport modulation between MHS and MNS erythrocytes.

PMID- 1390857
TI  - Transport of phospholipids between subcellular membranes of wild-type yeast cells
      and of the phosphatidylinositol transfer protein-deficient strain Saccharomyces
      cerevisiae sec 14.
AB  - The transfer of glycerophospholipids between microsomes and mitochondria, and
      from internal membranes to the plasma membrane of Saccharomyces cerevisiae was
      characterized. Cellular energy production was found to be essential for
      intracellular translocation of phospholipids, but neither a membrane potential
      nor an intact cytoskeleton are required for this process. Using the temperature
      sensitive mutant strain Saccharomyces cerevisiae sec 14, which is defective in
      the phosphatidylinositol transfer protein, it could be demonstrated that this
      protein is not involved in the transport of phosphatidylinositol and
      phosphatidylcholine from internal membranes to the plasma membrane. Our results
      also confirm earlier findings that phosphatidylinositol and phosphatidylcholine
      can be delivered to the plasma membrane in a process independent of the flux of
      vesicles competent for protein secretion.

PMID- 1390858
TI  - The influence of cholesterol 3-sulphate on phase behaviour and hydrocarbon order
      in model membrane systems.
AB  - Cholesterol 3-sulphate (CS) is a component of the intercellular lipid found in
      the uppermost layer of human epidermis (the 'stratum corneum') and is thought to
      play an important role in tissue cohesion. In this investigation we have compared
      the influence of cholesterol (CH) and CS on the gel-to-liquid crystalline phase
      behaviour, the polymorphic phase behaviour, and the hydrocarbon order profile in
      selected model membranes. It is shown that in sphingomyelin (SPM) systems, the
      presence of equimolar amounts of either CH or CS eliminates the gel-to-liquid
      crystalline transition as detected by calorimetry. Similarly, in 1-palmitoyl,2
      oleoyl-phosphatidylethanolamine (POPE) dispersions containing a perdeuterated
      palmitoyl chain (POPE-d31), it is shown that both CH and CS exert an ordering
      effect as determined by 2H-NMR techniques, however, CS is less potent at
      temperatures both above and below that of the main transition for the native
      phospholipid. Alternatively, in mixed systems containing
      dioleoylphosphatidylethanolamine (DOPE) and SPM (DOPE/SPM, 6:1 mol/mol) CH
      promotes thermotropic L alpha-->HII phase transitions, whereas CS stabilizes the
      bilayer organization. These bilayer stabilization effects can be diminished by
      addition of Ca2+. These effects are consistent with a larger area per molecule of
      CS as compared to CH, presumably related to the presence of the negatively
      charged sulphate moiety of CS.

PMID- 1390859
TI  - Incorporation of carotenoids in aqueous systems: uptake by cultured rat
      hepatocytes.
AB  - The in vitro investigations about carotenoid functions and metabolism are
      hindered by their hydrophobicity. In order to mimic as close as possible the
      physiological events, we prepared by rapid and easy methods sterile liposomes and
      emulsions containing carotenoids which are absorbed by cultured rat hepatocytes
      as a function of time and temperature. The lipid composition of the vesicles was
      shown to influence the carotenoid encapsulation.

PMID- 1390860
TI  - Substrate-specific differences in the rate of bile acid carrier reorientation:
      studies on human placental basal vesicles.
AB  - The initial rate of transport of the bile acid glycocholic acid (GCA) has been
      measured in influx and efflux across placental basal membrane vesicles, and the
      mechanism of inhibition of its transport by the analogue taurochenodeoxycholic
      acid (TCDCA) analysed kinetically. This analogue, although trans-stimulating GCA
      efflux, inhibits influx in a way which does not depend upon substrate
      concentration; moreover, its potency as an inhibitor is markedly influenced by
      whether it is placed on one or on both sides of the vesicles membrane. These
      findings can be accounted for by postulating that both GCA and TCDCA are
      translocated through the carrier, but that the rate of loaded carrier
      reorientation is higher than that of the free carrier only when loaded with TCDCA
      and not with GCA.

PMID- 1390863
TI  - Experimental evidence for the involvement of the cytoskeleton in mammalian cell
      electropermeabilization.
AB  - Chinese hamster ovary (CHO) cells and human erythrocytes were pulsed by using
      square-wave electric-field pulses. This treatment induced their permeabilization.
      This phenomenon appears to be a three-step process of creation, expansion and
      annihilation of permeated structures. Altering the cell cytoskeleton, either with
      drugs, such as colchicine, known to depolymerise the microtubules in CHO cells,
      or by high temperature shock to affect the spectrin-actin network in
      erythrocytes, induced no modification on the first two steps of the
      electropermeabilization process, but was associated with a dramatic decrease in
      the stability of the electro-induced permeated structures. These experimental
      observations support the hypothesis of an implication of cytoskeleton in
      electropermeabilization in agreement with thermodynamic conclusions.

PMID- 1390861
TI  - Vasopressin stimulation of vanadate-sensitive Na+ transport by liver plasma
      membrane vesicles. Evidence for regulation via phospholipase C and protein kinase
      C activities.
AB  - The rate of vanadate-sensitive 22Na+ uptake by isolated liver membrane vesicles,
      reflecting transport by Na+/K(+)-ATPase, was measured to study the role played by
      phospholipase C and protein kinase C in the regulation of this process by
      vasopressin. Na+ uptake was enhanced 2-3-fold by 100 nM [Arg8]vasopressin and the
      hormone effect was mimicked by 0.1 microM inositol 1,4,5-trisphosphate as well as
      by 1.0 microM myo-inositol. The stimulation by vasopressin was potentiated by
      phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis (5-10
      mU/ml). No effect of the bacterial enzyme was observed in the absence of the
      hormone. Phorbol myristate acetate (0.5-1 microM) suppressed the stimulation by
      vasopressin but had no effect in the absence of the hormone. High concentrations
      of bacterial phosphatidylinositol-specific phospholipase C (50-100 mU/ml) also
      antagonized the hormone stimulation. Staurosporine (50-100 nM) prevented the
      antagonistic effect of bacterial phospholipase C (50 mU/ml) and EGTA (1 mM)
      partially protected the hormonal stimulation in the presence of phorbol myristate
      acetate. Our results suggest that the stimulatory effect of vasopressin on Na+
      transport is mediated by phospholipase C and products derived from the inositol
      moiety of membrane phospholipids. Membrane-associated protein kinase C appears to
      be at least partially responsible for the desensitization to stimulation by
      vasopressin.

PMID- 1390862
TI  - Alcohols produce reversible and irreversible acceleration of phospholipid flip
      flop in the human erythrocyte membrane.
AB  - The slow, non-mediated transmembrane movement of the lipid probes
      lysophosphatidylcholine, NBD-phosphatidylcholine and NBD-phosphatidylserine in
      human erythrocytes becomes highly enhanced in the presence of 1-alkanols (C2-C8)
      and 1,2-alkane diols (C4-C8). Above a threshold concentration characteristic for
      each alcohol, flip rates increase exponentially with the alcohol concentration.
      The equieffective concentrations of the alcohols decrease about 3-fold per
      methylene added. All 1-alkanols studied are equieffective at comparable
      calculated membrane concentrations. This is also observed or the 1,2-alkane
      diols, albeit at a 5-fold lower membrane concentration. At low alcohol
      concentrations, flip enhancement is reversible to a major extent upon removal of
      the alcohol. In contrast, a residual irreversible flip acceleration is observed
      following removal of the alcohol after a treatment at higher concentrations. The
      threshold concentrations to produce irreversible flip acceleration by 1-alkanols
      and 1,2-alkane diols are 1.5- and 3-fold higher than those for flip acceleration
      in the presence of the corresponding alcohols. A causal role in reversible flip
      acceleration of a global increase of membrane fluidity or membrane polarity seems
      to be unlikely. Alcohols may act by increasing the probability of formation of
      transient structural defects in the hydrophobic barrier that already occur in the
      native membrane. Membrane defects responsible for irreversible flip-acceleration
      may result from alterations of membrane skeletal proteins by alcohols.

PMID- 1390864
TI  - Endoplasmic reticulum: the major contributor to the PDE peak in hepatic 31P-NMR
      spectra at low magnetic field strengths.
AB  - 31P-NMR spectra of liver in vivo, subcellular fractions and model systems were
      acquired in order to characterise further the hepatic phosphodiester peak seen at
      low magnetic field strengths previously shown to be predominantly due to
      phospholipid bilayers. The data obtained in this study in vitro suggested that
      the phospholipid membranes of the endoplasmic reticulum provide the dominant
      contribution to this phosphodiester peak. Support for this hypothesis was
      provided by experiments on rats. Phenobarbitone, which is known to induce
      proliferation of the endoplasmic reticulum produced a considerable increase in
      intensity of the phosphodiester peak in liver spectra in vivo.

PMID- 1390866
TI  - Effect of the sulfhydryl reagent thimerosal on cytosolic free Ca2+ and membrane
      potential of thymocytes.
AB  - The sulfhydryl reagent thimerosal at concentrations 5-100 microM has been found
      to induce a variety of changes in ion transport in rat thymocytes. In particular,
      [Ca2+]i increases about 10-fold from the basal level. The [Ca2+]i response to
      thimerosal displays a two-stage time course, with the main [Ca2+]i rise during
      the second stage. Evidence has been obtained for the depletion of intracellular
      Ca2+ pools in thimerosal-treated cells, however, Ca2+ mobilization from
      intracellular stores does not contribute significantly into [Ca2+]i rise.
      Thimerosal elicits permeability not only for Ca2+, but also for Mn2+ and Ni2+,
      which is Ca(2+)-dependent. We failed to get any evidence on thimerosal-induced
      inhibition of the plasma membrane Ca(2+)-ATPase. The induction of Ca2+ influx,
      rather than inhibition of Ca(2+)-ATPase, accounts for the disturbance of [Ca2+]i
      homeostasis in thimerosal-treated cells. Thimerosal also elicits changes in
      monovalent ion fluxes resulting in marked depolarization. The latter seems
      unrelated to the changes in [Ca2+]i and is suggested to be mediated both by
      increased permeability for Na+ and a decreased one for K+. Thimerosal
      significantly stimulates AA release from thymocytes. Evidence has been presented
      that AA metabolite(s), probably, LO product(s), may mediate the changes in the
      transport of mono- and divalent cations elicited by the sulfhydryl reagent.
      Prolonged treatment of thymocytes with thimerosal resulted in cell death.

PMID- 1390865
TI  - Developmental changes in hepatic basolateral membrane lipid composition and
      fluidity.
AB  - Membrane fluidity and lipid composition influence the activity of a variety of
      membrane proteins. Decreased rates of hepatic ion clearance are associated with
      the neonatal period. We postulated that hepatic basolateral membranes derived
      from suckling animals might be less fluid than those from adult animals.
      Basolateral membrane vesicles were prepared from the livers of 1-week-old (SBLMV)
      and adult (ABLMV) rats by a Percoll gradient method. Na+/K(+)-ATPase activities
      were similar in the two groups. Double bond index, cholesterol and
      cholesterol/phosphorus ratios were significantly higher in SBLMV compared with
      ABLMV, while lipid phosphorus and relative percentages of phospholipid subclasses
      did not differ. Fluorescence anisotropy measured using diphenylhexatriene as well
      as 2-(9-anthroyloxy)stearate was significantly greater in SBLMV compared with
      ABLMV, while measurements made with 12-(9-anthroyloxy)stearate were similar in
      both age groups. Mean excited state lifetimes, lifetime distributions, and
      rotational correlation times were similar in both groups. These data suggest that
      hepatic basolateral membranes derived from suckling rats are less fluid than
      those from adult animals and further suggest that this difference may be due to
      increased cholesterol in hepatic basolateral membranes derived from suckling
      animals.

PMID- 1390867
TI  - Characterization and chemical modification of the Na(+)-dependent bile-acid
      transport system in brush-border membrane vesicles from rabbit ileum.
AB  - The Na(+)-dependent uptake system for bile acids in the ileum from rabbit small
      intestine was characterized using brush-border membrane vesicles. The uptake of
      [3H]taurocholate into vesicles prepared from the terminal ileum showed an
      overshoot uptake in the presence of an inwardly-directed Na(+)-gradient ([Na+]out
      > [Na+]in), in contrast to vesicles prepared from the jejunum. The Na(+)
      dependent [3H]taurocholate uptake was cis-inhibited by natural bile acid
      derivatives, whereas cholephilic organic compounds, such as phalloidin,
      bromosulphophthalein, bilirubin, indocyanine green or DIDS - all interfering with
      hepatic bile-acid uptake - did not show a significant inhibitory effect.
      Photoaffinity labeling of ileal membrane vesicles with 3,3-azo- and 7,7-azo
      derivatives of taurocholate resulted in specific labeling of a membrane
      polypeptide with apparent molecular mass 90 kDa. Bile-acid derivatives inhibiting
      [3H]taurocholate uptake by ileal vesicles also inhibited labeling of the 90 kDa
      polypeptide, whereas compounds with no inhibitory effect on ileal bile-acid
      transport failed to show a significant effect on the labeling of the 90 kDa
      polypeptide. The involvement of functional amino-acid side-chains in Na(+)
      dependent taurocholate uptake was investigated by chemical modification of ileal
      brush-border membrane vesicles with a variety of group-specific agents. It was
      found that (vicinal) thiol groups and amino groups are involved in active ileal
      bile-acid uptake, whereas carboxyl- and hydroxyl-containing amino acids, as well
      as tyrosine, histidine or arginine are not essential for Na(+)-dependent bile
      acid transport activity. The irreversible inhibition of [3H]taurocholate
      transport by DTNB or NBD-chloride could be partially reversed by thiols like 2
      mercaptoethanol or DTT. Furthermore, increasing concentrations of taurocholate
      during chemical modification with NBD-chloride were able to protect the ileal
      bile-acid transporter from inactivation. These findings suggest that a membrane
      polypeptide of apparent M(r) 90,000 is a component of the active Na(+)-dependent
      bile-acid reabsorption system in the terminal ileum from rabbit small intestine.
      Vicinal thiol groups and amino groups of the transport system are involved in
      Na(+)-dependent transport activity, whereas other functional amino acids are not
      essential for transport activity.

PMID- 1390868
TI  - The human T-cell leukemia virus (HTLV) transactivator (Tax) protein.

PMID- 1390870
TI  - Molecular cytogenetics of human neuroblastoma.

PMID- 1390871
TI  - Great expectations: protein tyrosine phosphatases in cell regulation.

PMID- 1390869
TI  - Molecular mimicry of erythropoietin by the spleen focus-forming virus gp55
      glycoprotein: the first stage of Friend virus-induced erythroleukemia.

PMID- 1390872
TI  - Membrane lipids of human peripheral nerve and spinal cord.
AB  - Major membrane lipids were determined in specimens of human peripheral nerve
      (cauda equina) and spinal cord of 10 subjects aged 20-70 years. The same lipids
      were also assayed in myelin from the same tissues isolated with two different
      procedures and in myelin of cauda equina from 3 subjects aged 17-91 years
      isolated with a third method. The concentrations (mean and standard deviation) of
      phospholipids were 90 +/- 11 and 96 +/- 9 nmol/g fresh weight; of cholesterol 70
      +/- 15 and 101 +/- 16; of cerebroside 19 +/- 3 and 41 +/- 7; of sulfatide 10 +/-
      1 and 11 +/- l; and of gangliosides 0.80 +/- 0.08 and 0.40 +/- 0.05 N in cauda
      equina and spinal cord, respectively. The proportion of ethanolamine
      phosphoglyceride was lower and that of sphingomyelin higher in cauda equina than
      in spinal cord. The myelin of peripheral nerve and spinal cord contained almost
      the same proportions of lipids as the whole tissue. The protein-bound sialic acid
      content was 3-fold higher than the lipid-bound sialic acid content in cauda
      myelin. The fatty acid patterns of choline, ethanolamine, inositol and serine
      phosphoglycerides of spinal cord and its myelin, were very similar to those of
      cerebral white matter, while the phosphoglycerides of cauda equina had higher
      proportions of monoenoic acids and lower proportions of polyunsaturated fatty
      acids. The fatty acid patterns of sphingomyelin, cerebroside and sulfatide of
      spinal cord were similar to those of cerebral white matter, while those of cauda
      equina contained significantly more saturated fatty acids. This suggests that the
      lipid and fatty acid compositions of peripheral nerve are particularly suitable
      for the formation of a tightly packed myelin membrane which can be a powerful
      shield against infections and other injuries.

PMID- 1390874
TI  - 12-Lipoxygenase from rat basophilic leukemia cells, an oxygenase with leukotriene
      A4-synthase activity.
AB  - Rat basophilic leukemia cells exhibit 12-lipoxygenase activity only upon cell
      disruption. 12-Lipoxygenase may also possess 15-lipoxygenase activity, as is
      indicated by the formation of low amounts of 15(S)-HETE, in addition to the
      predominant product 12(S)-HETE, upon incubation of partially purified 12
      lipoxygenase with arachidonic acid. With 5(S)-HPETE as substrate not only 5(S),
      12(S)-diHETE and 5(S), 15(S)-diHETE are formed, but also LTA4, as was indicated
      by the presence of LTA4-derived LTB4-isomers. 12-Lipoxygenase from rat basophilic
      leukemia cells has many features in common with 12-lipoxygenase from bovine
      leukocytes. As was suggested for the latter enzyme, 12-lipoxygenase from rat
      basophilic leukemia cells may represent the remaining LTA4-synthase activity of 5
      lipoxygenase, of which the 5-dioxygenase activity has disappeared upon cell
      disruption. Such a possible shift from 5-lipoxygenase activity to 12-lipoxygenase
      activity could not simply be induced by interaction of cytosolic 5-lipoxygenase
      with a membrane fraction after cell disruption, but may involve release of
      membrane-associated 5-lipoxygenase upon disruption of activated rat basophilic
      leukemia cells.

PMID- 1390873
TI  - Myocardial carnitine palmitoyltransferase of the mitochondrial outer membrane is
      not altered by fasting.
AB  - The regulation of heart carnitine palmitoyltransferase was studied during the
      transition to the fasting state. Using decanoyl-CoA or palmitoyl-CoA as
      substrates, we found no differences in carnitine palmitoyltransferase activity or
      in its sensitivity to inhibition by malonyl-CoA between fed and fasted states. No
      cooperativity was seen with either substrate, and the malonyl-CoA-induced shift
      to sigmoid kinetics normally observed with liver mitochondria was not obvious
      with heart mitochondria. Analysis of malonyl-CoA inhibition data revealed that
      mitochondria from rat heart exhibited incomplete maximum inhibition of carnitine
      palmitoyltransferase (partial inhibition). Homogenization of intact liver
      mitochondria resulted in a similar pattern of incomplete inhibition and suggested
      that the malonyl-CoA-insensitive carnitine palmitoyltransferase of the inner
      membrane was also being assayed. Carnitine palmitoyltransferase in mitochondrial
      outer membranes, isolated from the heart, proved to be extremely sensitive to
      malonyl-CoA inhibition and had maximum inhibition values of 90-100% with either
      decanoyl-CoA or palmitoyl-CoA as substrates, but fasting had no effect. Fasting
      produced no change in the Ki for malonyl-CoA (0.10 +/- 0.04 and 0.14 +/- 0.02
      microM for the fed and fasted groups, respectively). Acyl-CoA chain length
      specificity was C10 greater than C16 greater than C14 greater than C12 greater
      than C18 = C8 for carnitine palmitoyltransferase in heart mitochondrial outer
      membranes. It is concluded that the regulation of carnitine palmitoyltransferase
      of heart mitochondrial outer membranes differs from regulation of the liver
      enzyme in three characteristics--the heart enzyme (a) has greater sensitivity to
      malonyl-CoA inhibition, (b) is resistant to the effects of fasting and (c) has
      somewhat different acyl-CoA substrate specificity.

PMID- 1390875
TI  - Spontaneous hypercholesterolemia in cynomolgus monkeys: evidence for defective
      low-density lipoprotein catabolism.
AB  - Spontaneously hypercholesterolemic (SH) cynomolgus monkeys were identified that
      have average plasma cholesterol of 202 mg/dl, while that in normal monkeys is 119
      mg/dl. The LDL from these SH monkeys have lower affinity for fibroblast LDL
      receptors in vitro. The amount of LDL2 (1.030 mean value of d 1.063 g/ml)
      required to displace 50% of [125I]LDL was 3.8 micrograms/ml for normal LDL2 and
      6.6 micrograms/ml for SH-LDL2. The binding affinity of LDL1 (1.019 mean value of
      d 1.030 g/ml) was the same in normal and SH animals. LDL turnover experiments
      showed that the SH monkeys were comprised of two populations. Normal LDL2 was
      cleared much slower in two of the SH monkeys than in normocholesterolemic
      animals, suggesting that these two animals have an LDL receptor defect. However,
      LDL2 isolated from these two SH monkeys was cleared normally in normal monkeys.
      LDL2 isolated from two other SH monkeys is cleared slower than is normal LDL2 in
      normal animals, suggesting that these animals have an LDL defect. Thus, the
      hypercholesterolemia of these SH monkeys is associated with defective LDL
      catabolism; two animals appear to have functionally defective LDL receptors, and
      two animals appear to have functionally defective LDL.

PMID- 1390877
TI  - Prolonged circulation time in vivo of large unilamellar liposomes composed of
      distearoyl phosphatidylcholine and cholesterol containing amphipathic
      poly(ethylene glycol).
AB  - The effect of poly(ethylene glycol) (PEG) on the circulation time of liposomes in
      mice was examined by employing amphipathic PEGs (phosphatidylethanolamine (PE)
      derivatives of PEG) with average molecular weights of 1000, 2000, 5000 and
      12,000. The activity of dioleoyl phosphatidylethanolamine-PEG (DOPE-PEG) in
      prolonging the circulation time of egg phosphatidylcholine/cholesterol large
      unilamellar liposomes (ePC/CH LUVs) (200 nm) was proportional to the molecular
      weight of PEG, i.e., 12000 = 5000 greater than 2000 greater than 1000. On the
      other hand, inclusion of distearoylphosphatidylethanolamine-PEG (DSPE-PEG) or
      dipalmitoyl-phosphatidylethanolamine-PEG (DPPE-PEG) of low molecular weight such
      as 1000 and 2000 in distearoylphosphatidylcholine (DSPC)/CH LUVs or dipalmitoyl
      phosphatidylcholine (DPPC)/CH LUVs effectively increased their blood circulation
      time. At least 3 mol% of amphipathic PEG in liposomes was required for activity.
      Addition of CH, which has a bilayer-tightening effect, to DSPC/CH/DSPE-PEG2000
      LUVs further increased the blood residence time. A size of less than 300 nm was
      essential for prolonging the residence time of amphipathic PEG-containing
      liposomes in blood. DSPC/CH/DSPE-PEG2000 LUVs (1:1:0.13, m/m) containing 6 mol%
      of PEG and 200 nm in diameter remained in the circulation for over 24 h after
      injection and may be clinically useful for sustained release of an entrapped drug
      in the bloodstream and for drug accumulation in solid tumors.

PMID- 1390876
TI  - Changes in fatty acid composition in rat blood and organs after infusion of
      eicosapentaenoic acid ethyl ester.
AB  - An infusible emulsion of 10% eicosapentaenoic acid ethyl ester (EPA-EE, 99.2%
      pure) was prepared. Three ml of the emulsion was infused into tail veins of 20
      Wistar rats weighing approx. 300 g. They were killed 1 h, 6 h, 24 h, 3 d and 7 d
      after the infusion, and fatty acid composition of various organs and plasma was
      analyzed along with that of control rats. There was no lipidosis in any organs of
      any rats. It was estimated that not less than 98% of infused EPA was cleared from
      plasma during the first hour after the infusion. EPA concentrations reached their
      peaks within 6 h after EPA infusion in plasma lipid fractions and in the
      phospholipid fraction of liver, heart, lung, kidney and spleen. The fatty acid
      composition of the phospholipid fraction of heart was very stable, and was not
      altered by EPA infusion except for a very slight increase in EPA at 1 h after the
      infusion (0.18% at 0 h to 0.56%). However, EPA concentrations increased markedly
      in the free fatty acid fraction of heart at 1 h after the infusion (0.15% at 0 h
      to 4.23%). Arachidonic acid concentrations decreased significantly within 24 h in
      the phospholipid fraction of organs except for heart. EPA emulsion might be
      useful for patients in whom a rapid increment in EPA in tissues is beneficial.

PMID- 1390878
TI  - The influence of medium components on Cu(2+)-dependent oxidation of low-density
      lipoproteins and its sensitivity to superoxide dismutase.
AB  - The extent of in vitro Cu(2+)-dependent oxidation of low-density lipoproteins
      (LDL) has been reported to vary widely depending upon reaction conditions. In
      this study, the effect of proteins and amino acids on Cu(2+)-induced LDL
      oxidation was examined. Treatment of LDL with 5 microM CuSO4 for 18 h in either
      phosphate-buffered saline (PBS) or Ham's F-10 medium resulted in extensive
      oxidation as determined by the content of thiobarbituric acid reactive substances
      (TBARS) and by increased lipoprotein electronegativity. In PBS, oxidation was
      entirely blocked by histidine and the tripeptide, gly-his-lys (GHK). Oxidation
      was also prevented by bovine serum albumin, but superoxide dismutase (SOD)
      provided only 20% protection. Both proteins bound similar amounts of Cu2+, but
      albumin appeared to be a more effective peroxyl radical trap as evidenced by its
      ability to prevent LDL oxidation induced by 2,2'-azo-bis(2-amidinopropane
      hydrochloride). In F-10 medium, SOD had marked inhibitory effects, in contrast to
      PBS. The addition of disulfides to PBS markedly enhanced the ability of SOD to
      inhibit oxidation. These results indicate that medium components which affect
      Cu2+ availability influence LDL oxidation and suggest that albumin is ideally
      suited as a plasma antioxidant to prevent oxidative modification of LDL.
      Furthermore, in certain instances, the inhibitory effects of SOD may be
      attributable to effects such as Cu2+ binding rather than dismutation of
      superoxide.

PMID- 1390880
TI  - Altered positional specificity of human plasma lecithin-cholesterol
      acyltransferase in the presence of sn-2 arachidonoyl phosphatidyl cholines.
      Mechanism of formation of saturated cholesteryl esters.
AB  - The positional specificity of purified human lecithin-cholesterol acyltransferase
      (LCAT) was studied by analyzing the labeled cholesteryl ester (CE) species formed
      in the presence of proteoliposome substrates containing mixed chain
      phosphatidylcholine (PC) species, labeled cholesterol and apoprotein A-I. Whereas
      over 90% of the acyl groups used for CE synthesis were derived from the sn-2
      position of most of the naturally occurring PC substrates, about 75% of the CE
      species formed in the presence of sn-1-myristoyl 2-arachidonoyl PC, sn-1
      palmitoyl-2-arachidonoyl (PAPC) and sn-1-palmitoyl 2-docosahexaenoyl PC were
      derived from the sn-1-position. On the other hand, rat LCAT utilized mostly sn-2
      acyl group from either PAPC or from sn-1-palmitoyl 2-linoleoyl PC. The positional
      specificity of the human enzyme was not affected by the alteration in the matrix
      fluidity, type of the apoprotein activator used, or by the free cholesterol/PC
      ratio in the substrate. These results show that the positional specificity of
      human plasma LCAT is altered in the presence of sn-2-arachidonoyl PC, or sn-2
      docosahexaenoyl PC, probably due to steric restrictions at the active site, and
      this may account for the formation of disproportionately high concentrations of
      saturated CE, and low concentrations of long-chain polyunsaturated CE in human
      plasma, relative to the composition of sn-2-acyl groups in plasma PC.

PMID- 1390879
TI  - 7 alpha-hydroxylation of 27-hydroxycholesterol in human liver microsomes.
AB  - Human liver microsomes were found to catalyze 7 alpha-hydroxylation of 27
      hydroxycholesterol at a rate of up to about 0.2 nmol/mg protein per min. The
      product of the reaction, 5-cholestene-3 beta, 7 alpha, 27-triol, was identified
      by means of combined gas chromatography-mass spectrometry. Liver microsomes from
      two patients with an upregulated cholesterol 7 alpha-hydroxylase, did not have
      higher 7 alpha-hydroxylase activity towards 27-hydroxycholesterol than those from
      untreated patients, suggesting that the 7 alpha-hydroxylase active towards 27
      hydroxycholesterol is not the same as that active towards cholesterol. The
      mitochondrial fraction of liver from untreated patients and patients treated with
      cholestyramine, had negligible 7 alpha-hydroxylase activity towards 27
      hydroxycholesterol less than 0.01 nmol/mg protein per min). The results are in
      accord with the possibility that there is a pathway to bile acids in human liver
      in which the first step is a 27-hydroxylation of cholesterol.

PMID- 1390882
TI  - Gene structure and expression.

PMID- 1390881
TI  - Structure of polymerizable lipid bilayers. V. Synthesis, bilayer structure and
      properties of diacetylenic ether and ester lipids.
AB  - Four diacetylenic phosphatidylcholines (PC's) have been synthesized and the
      structures of bilayers of these lipids have been determined at low resolution by
      low-angle X-ray diffraction. The PC's all have 18-carbon chains but differ with
      respect to the ether/ester linkage at the sn-1 and sn-2 positions and the
      relative position of the diacetylene moiety: diester-PC (1): 1,2-bis(octadeca
      4',6'-diynoyl)-sn-glycero-3-phosphocholine diester-PC (2): 1-(octadeca-4',6'
      diynoyl)-2-(octadeca-5',7'-diynoy l)-sn- glycero-3-phosphocholine diester-PC (3):
      1,2-bis(octadeca-8',10'-diynoyl)-sn-glycerol-3-phosphocholin e diether-PC (4): 1
      O-(octadeca-4',6'-diynyl)-2-O-(octadeca-5",7"-din yl)-sn- glycero-3
      phosphocholine Only (1) exhibits the typical bilayer profile, whereas (2), (3)
      and (4) show evidence of interdigitation and/or significant disorder. Only (1)
      polymerized effectively upon illumination with 254 nm light, turning deep blue in
      seconds, indicating the formation of long, well-ordered polydiacetylenic
      structures. Liposomes of these derivatives were tested for permeability by
      osmotic swelling. Polymerized liposomes of (1) underwent osmotic swelling with
      urea, glycerol, and acetamide more rapidly than did liposomes of stearoyl-oleoyl
      PC, but the initial rates of osmotic swelling of polymerized liposomes of (1)
      were 3-10-times lower than those of unpolymerized liposomes of (1). Blue
      polymerized multilayer samples of (1) exhibited an irreversible thermochromic
      transition to red at approx. 40 degrees C. Differential scanning calorimetry with
      liposome suspensions of (1) revealed an endotherm at 28.3 degrees C with a
      transition enthalpy of 40 J/g. PC (1) is a potentially useful diacetylenic lipid
      which exhibits facile, complete polymerization and a bilayer thickness comparable
      to that of biomembrane lipids.

PMID- 1390883
TI  - Transcription factors and liver-specific genes.

PMID- 1390884
TI  - Molecular, functional and structural properties of an archaebacterial elongation
      factor 2.
AB  - The elongation factor 2 (aEF-2) from the extreme thermo-acidophilic
      archaebacterium Sulfolobus solfataricus, is the only cytosolic target protein
      which is ADP-ribosylated by diphtheria toxin in presence of NAD. Once ADP
      ribosylated, aEF-2 is no longer able to sustain poly(Phe) synthesis in vitro. aEF
      2 displays a great thermoresistance: at the growth temperature of the
      archaebacterium, 87 degrees C, its half-life is 3 h. The amino acid sequence of
      the N-terminal region of aEF-2 has been determined up to residue 22. In the first
      15 positions such a sequence is identical to that of EF-2 from Sulfolobus
      acidocaldarius and very similar to that of EF-2 from other archaebacteria or
      eukaryotes. The same is true for the primary structure of the peptide containing
      the ADP-ribosylation site. The fact that the primary structure of EF-2 at the ADP
      ribosylation site is highly conserved ensures either the correct recognition of
      the histidine residue by the enzymes involved in its modification to diphthamide,
      or the proper interaction with the diphtheria toxin.

PMID- 1390885
TI  - The bovine protamine 2 gene: evidence for alternative splicing.
AB  - Protamine 2 (PRM2) is a low molecular weight arginine-rich protein which is
      present in haploid spermatogenic cells of human and mouse. Although the bull PRM2
      gene is translated and transcribed at low levels, the protein could not be
      detected. The gene was isolated from a cosmid library and was found to consist of
      two exons (298 and 50 bp, respectively) interrupted by an intron of 142 bp. As
      compared to the PRM2 genes of man, mouse and rat the bovine gene lacks a highly
      conserved sequence coding for the amino acids RLHRIH. Furthermore, primer
      extension experiments on bull PRM2 mRNA and sequencing of junction fragments
      revealed alternative splicing of mRNA resulting in two putative isoforms of the
      protein. The most abundant transcript is spliced at the conserved splice donor
      site found in exon 1 at position 236 giving rise to an in-frame deletion of 63 bp
      as compared to the cDNA sequence (Maier et al. (1990) Nucleic Acids Res. 18, 1249
      1254). The less abundant longer mRNA was not detectable by radioactive primer
      extension. The corresponding cDNA was obtained by performing PCR with reverse
      transcribed bull testis RNA or with a spermatid specific cDNA library.
      Alternative splicing should result in an addition of 21 nonpolar amino acids in
      the derived polypeptide and an altered protein conformation and function.

PMID- 1390887
TI  - Readthrough of the Bacillus subtilis stop codon produces an extended enzyme
      displaying a higher polymerase activity.
AB  - It has been generally accepted that the structural sacB gene of Bacillus subtilis
      levansucrase encodes a 50,000 Da extracellular protein. However, examination of
      the DNA sequence of the sacB flanking regions shows a putative open reading frame
      coding for a 20 amino acid peptide downstream immediately following the terminal
      TAA stop codon. By site-directed mutagenesis we have changed this stop codon to a
      glutamine codon. This stop codon readthrough leads to the synthesis and secretion
      by B. subtilis of a levansucrase possessing an extended polypeptide chain. The
      extended levansucrase has a molecular weight of 53,000 with a new carboxyl
      terminus, rich in basic and hydrophobic amino acids and possessing one cysteine
      residue. This enzyme synthesizes fructosyl polymer levan of higher molecular
      weight than the shorter levansucrase. The increase in molecular weight was
      achieved by increasing the number of branches. These results suggest that the C
      terminal part of the enzyme plays a specific role in the degree of branching of
      the synthesized polymer. Moreover, the extended enzyme is able to form an active
      dimer from two polypeptide chains linked by an S-S bridge.

PMID- 1390886
TI  - Magnetic field-induced changes in specific gene transcription.
AB  - Magnetic fields are physical, environmental agents that have been shown to
      produce a variety of responses in cellular and animal studies, including general
      changes in gene transcription. In this study, the nuclear run-off assay has been
      employed to assess alterations in specific gene transcription in CEM-CM3 T
      lymphoblastoid cells exposed for 15-120 min to a 1 gauss sinusoidal magnetic
      field at 60 Hz. Time-dependent and cell density-dependent changes in the
      transcription of c-fos, c-jun, c-myc and protein kinase C (beta-form) have been
      observed and quantitated. Additionally, changes in transcript levels, assessed by
      slot-blot analysis, have been found to parallel the changes in gene
      transcription. These data suggest an important role for magnetic field exposure
      in altering cellular processes.

PMID- 1390889
TI  - Recombinant mouse tumor necrosis factor expressed in mammalian cells: effect of
      glycosylation on cytotoxic activity.
AB  - A mouse tumor necrosis factor-alpha (TNF) expression vector, pTNFNeo, was
      constructed by inserting a 1.3 kb cDNA coding for a full structural region of
      mouse TNF into an expression plasmid BCMGSNeo. COS7 cells were transfected with
      the pTNFNeo and a G418-resistant transfectant, BK-2, which stably secreted lytic
      activity to L929 cells was cloned. The lytic activity in the BK-2 culture spent
      medium reached up to 6000 U/ml, and was completely and specifically inhibited
      with antiserum to mouse TNF. Gel filtration chromatography and Western blot
      analysis indicated that the recombinant TNF in the medium existed in associated
      forms composed of a mixture of 22 kDa and 17.5 kDa components. Glycopeptidase F
      digestion indicated that the 22 kDa species was an N-glycosylated form of the
      17.5 kDa species. Specific activities of the 22 kDa and the 17.5 kDa species
      isolated were 6.9 x 10(5) U/mg and 8.1 x 10(6) U/mg, respectively, suggesting
      that carbohydrate moiety impaired the lytic activity.

PMID- 1390888
TI  - Structure and expression of gene coding for a pupal cuticle protein of Bombyx
      mori.
AB  - A specific protein termed as PCP accumulates in the newly synthesized pupal
      cuticle of the silkworm, Bombyx mori. We have cloned the genomic sequence
      encoding PCP and analyzed its structure. The PCP gene comprises two exons
      interspersed by a single intron approx. 5.8 kb in length. Transcription
      initiation sites of the PCP gene were located at nucleotide level. The 5'
      flanking region of the gene contains a sequence homologous to the Pit-1 DNA
      recognition element of the rat prolactin and growth hormone genes. The
      developmental profile of the PCP precursor RNA in epidermal cells showed that the
      biosynthesis of PCP is regulated at the transcriptional level in a stage- and
      tissue-specific fashion during post-embryonic development. Administration of 20
      hydroxyecdysone to the isolated abdomens prepared from the early fifth instar
      larvae provoked the accumulation of PCP mRNA in epidermis, suggesting that the
      molting hormone triggers the expression of PCP gene.

PMID- 1390890
TI  - Yeast ribosomal proteins: XIV. Complete nucleotide sequences of the two genes
      encoding Saccharomyces cerevisiae YL16.
AB  - We isolated and sequenced YL16A and YL16B encoding ribosomal protein YL16 of
      Saccharomyces cerevisiae. The two nucleotide sequences within coding regions
      retain 91.1% identity, and their predicted sequences of 176 amino acids show
      93.8% identity. Out of the ribosomal protein sequences from various organisms
      currently available, no counterpart to YL16 could be found.

PMID- 1390891
TI  - Molecular cloning and characterization of genes encoding rat pancreatic
      cholecystokinin (CCK)-releasing peptide (monitor peptide) and pancreatic
      secretory trypsin inhibitor (PSTI).
AB  - The genes encoding a rat pancreatic cholecystokinin (CCK)-releasing peptide
      (monitor peptide) and its structurally related peptide, rat pancreatic secretory
      trypsin inhibitor (PSTI), have been isolated and sequenced. The two genes share
      extremely high sequence similarity in the 5' flanking regions, suggesting that
      these regions may be responsible for the characteristic coordinate expression of
      the two peptides.

PMID- 1390892
TI  - Isolation and nucleotide sequence of cecropin B cDNA clones from the silkworm,
      Bombyx mori.
AB  - Two cDNA clones encoding cecropin B, an antibacterial protein, were isolated from
      a fat body cDNA library of the silkworm, Bombyx mori. Amino acid sequences of
      these clones, deduced from nucleotide sequences, were identical, including signal
      peptide regions. However, the nucleotide sequences were different at 30
      positions. Deduced amino acid sequences of Bombyx mori cecropin B showed higher
      homology with cecropins from Lepidoptera than with those from Diptera.

PMID- 1390893
TI  - Molecular cloning of the E1 beta subunit of the rat branched chain alpha-ketoacid
      dehydrogenase.

PMID- 1390894
TI  - Isolation and characterization of the rat gene encoding ornithine
      aminotransferase.
AB  - Herein we describe the isolation and characterization of the rat gene encoding
      ornithine aminotransferase (rOAT). Six unique genomic clones were characterized
      and assigned to two nonoverlapping contigs representing approx. 33 kb of the rat
      genome. The 5' contig contains the rOAT promoter, exons 1 and 3, and a portion of
      exon 4; an exon corresponding to exon 2 of the human OAT gene (hOAT) was not
      identified. The rOAT promoter contains several putative regulatory elements in
      positions similar to hOAT. The 3' contig contains exons 7 through 11 in their
      entirety. Data presented and discussed herein suggest that approx. 3.0 kb of
      uncloned genomic DNA, containing the remainder of exon 4 and all of exons 5 and
      6, separate the two contigs. Together, these data suggest that rOAT extends over
      approx. 20 kb and is organized into at least 10 exons, thereby closely resembling
      hOAT in size and exon/intron organization. Isolation of rOAT provides an
      important tool for examining the molecular mechanisms through which estrogen and
      thyroid hormone regulate transcription of this gene in a cell-type specific
      manner.

PMID- 1390895
TI  - cDNA sequence for rat dermatan sulfate proteoglycan-II (decorin).
AB  - A cDNA clone for dermatan sulfate proteoglycan-II, or decorin, has been isolated
      from a rat uterus library and sequenced. The cDNA and deduced amino acid
      sequences are 79 and 77% identical to the previously reported human and bovine
      sequences, respectively. The rat protein contains potential attachment sites for
      two glycosaminoglycan chains and four N-linked oligosaccharides, six conserved
      cysteine residues and multiple repeats of a leucine-rich sequence, LXXLXLXXNXL/I.
      Overlapping the C-end of one of these repeats is an NKISK sequence, which has
      been implicated in binding to fibronectin.

PMID- 1390896
TI  - The primary structure of rat rig/ribosomal protein S15 gene.
AB  - We have isolated rat rig/ribosomal protein S15 gene from a DNA library derived
      from a rat insulinoma and determined the complete nucleotide sequence. The rat
      rig/S15 gene is composed of four exons and three introns spanning 2 kbp and
      exhibits distinctive structural features unique for a ribosomal protein gene.

PMID- 1390897
TI  - Platelet adhesion to collagen-coated wells: analysis of this complex process and
      a comparison with the adhesion to matrigel-coated wells.
AB  - The mechanisms of platelet adhesion to collagen type III-coated wells and
      Matrigel-coated wells were analyzed. The adhesion of 51Cr-labeled platelets to
      collagen-coated wells showed a biphasic pattern. The early stage of adhesion was
      inhibited by antibodies against platelet glycoprotein(GP)s Ia/IIa and VI. The
      later stage of platelet adhesion was inhibited by an antibody against the
      GPIIb/IIIa complex and a concomitant release of 14C-labeled serotonin was
      observed. The percentage of adhered platelets was increased when a higher
      platelet concentration was added in the reaction medium. These results indicated
      that the adhesion assay of platelets to collagen-coated wells was composed of two
      reactions: the first one is the platelet-collagen interaction that depends on
      GPIa/IIa and GPVI on the platelet surface; and the second reaction is the
      platelet-platelet interaction, platelet aggregation, which depends on GPIIb/IIIa.
      The adhesion of platelets to Matrigel-coated wells was indicated to involve
      platelet-Matrigel interactions that were partly dependent on the laminin in the
      Matrigel solution.

PMID- 1390898
TI  - Skeletal muscle Pi transport and cellular [Pi] studied in L6 myoblasts and rabbit
      muscle-membrane vesicles.
AB  - In the rat skeletal myoblast line L6 and in a rabbit skeletal muscle sarcolemma/t
      tubule vesicle preparation, [32P]Pi uptake was largely dependent on the
      transmembrane Na gradient. Na-dependent [32P]Pi uptake had a hyperbolic
      relationship to [Pi] and [Na], being half-maximal at 0.2-0.3 mM [Pi] and at 25-40
      mM [Na]. In vesicles the Na-dependence suggests that approx. two Na are
      transported with each Pi, but the inhibition of [32P]Pi uptake at high pH
      suggests that the Pi monoanion is the transported form. Together these imply
      electrogenic transport and this is confirmed by the results of manipulating the
      vesicle membrane potential. Thus, electrogenic Na-Pi co-transport exploits both
      the sodium gradient and the cell membrane potential to maintain muscle cellular
      [Pi] against an unfavourable electrochemical gradient. The low [Pi] for half
      maximal flux may partly explain the small effect of altered extracellular [Pi] on
      cellular [Pi]. In L6 myoblasts most 32P was first detectable in an organic
      phosphate pool rather than cellular Pi, while the specific activity of cell Pi
      rapidly reached 40% of that of extracellular Pi and was stable for at least 3 h.
      These results are discussed in terms of the organisation of cellular phosphate
      metabolism.

PMID- 1390899
TI  - Antiproliferative effect of phorbol esters on MCF-7 human breast adenocarcinoma
      cells: relationship with enhanced expression of transforming growth-factor-beta
      1.
AB  - In human breast carcinoma MCF-7 cells, phorbol diesters inhibit proliferation and
      induce cell maturation. We have recently reported that exogenous TGF-beta 1
      reverses the resistance of a breast adenocarcinoma MCF-7 subline (MCF-7:RPh-4) to
      these phorbol ester effects. Here, we investigated the involvement of TGF-beta 1
      in the PKC-mediated inhibition of breast-cancer cell proliferation. Parental MCF
      7-conditioned medium contained a 20-fold higher transforming activity on NRK-49F
      fibroblasts than the TPA-resistant subline. TPA increased TGF-beta activity in
      MCF-7 conditioned medium. MCF-7 cells also expressed more TGF-beta 1 mRNA than
      the resistant subline. TPA induced a dose-dependent increase in TGF-beta 1 mRNA
      levels that paralleled the inhibitory effect on MCF-7 proliferation. The lower
      level of TGF-beta mRNA expression in TPA resistant subline was not modified after
      addition of TPA, but was significantly increased in the presence of exogenous TGF
      beta 1. These data argue in favor of a role of endogenous TGF-beta 1 in the
      maturation process induced by protein kinase C activation.

PMID- 1390900
TI  - What dual-action agents reveal about acid secretion: a combined experimental and
      modeling analysis.
AB  - A previously described simple mathematical model for gastric acid secretion is
      employed to characterize the acid secretion response to thiocyanate and
      omeprazole, two partially conservative inhibitors that inhibit both the formation
      and translocation of acid. In addition, the effect of dithiothreitol on the
      omeprazole inhibition was investigated. The model parameters were estimated from
      four data sets by a non-linear least squares procedure: a dynamic (time
      dependent) set, made up of individual acid secretion rate curves; and three
      integral (time-independent) sets consisting of the curves of acid secreted and
      suppressed above and below baseline, respectively, and the index of conservation,
      all three as functions of agent exposure. At the translocation step the
      inhibition function was the same for the two inhibitors, and though similar at
      the formation step, they differ in that a Hill coefficient larger than unity is
      necessary in the thiocyanate inhibition function of the acid formation.
      Dithiothreitol protects only the formation step from inhibition by omeprazole.
      Hence, the binding sites for omeprazole are different for formation and
      translocation. This study exemplifies a non-invasive method for the investigation
      of the mechanism of gastric acid secretion following perturbation by external
      agents.

PMID- 1390901
TI  - Interleukin-1 beta enhances the response of human articular chondrocytes to
      extracellular ATP.
AB  - It has been observed that both interleukin-1 (IL-1) and extracellular ATP
      stimulate the production of prostaglandin E (PGE) by human articular chondrocytes
      in monolayer culture. The combined effects of recombinant human IL-1 beta and ATP
      were therefore studied using these cells. IL-1 beta rapidly enhanced the response
      to a maximally effective concentration of ATP (100 microM). On continuous
      exposure of the cells to the cytokine, its effect was greatest after approx. 24 h
      and tended to decline thereafter. The enhancement of the response to 100 microM
      ATP by IL-1 beta was dose-dependent. Removal of IL-1 beta prior to treating the
      cells with 100 microM ATP did not affect the degree of enhancement of the
      response. The effect of the cytokine on the response to suboptimal concentrations
      of extracellular ATP was also tested. IL-1 beta lowered the minimum concentration
      of ATP required to elicit an increase in the production of PGE by human articular
      chondrocytes. These findings are of interest, since they indicate a synergistic
      interaction between a cytokine and a purinergic agonist. Moreover, since both the
      sensitivity of the cells to extracellular ATP and the maximum response to this
      agent were enhanced, it is possible that IL-1 modulates more than one step in the
      process of P2-purinoceptor-mediated stimulation of PGE production. These
      observations may be relevant to the pathogenesis of some forms of arthritis.

PMID- 1390902
TI  - A retrovirus encoding the v-fps protein-tyrosine kinase induces factor
      independent growth and tumorigenicity in FDC-P1 cells.
AB  - There is increasing evidence that protein-tyrosine kinases play pivotal roles in
      the response to growth-factor signals. The cytoplasmic tyrosine kinase c-fps/fes,
      due to its restricted expression in hematopoietic tissue, is likely to
      participate in hematopoietic growth-factor signalling. We have introduced a
      retrovirus containing an activated fps gene (encoding P130gag-fps) into the
      growth factor-dependent myeloid cell line FDC-P1. Clonal cell lines were derived
      by selection for a marker gene coding for G418 resistance in the absence or
      presence of the hematopoietic growth factor IL-3. G418 resistant clones expressed
      P130gag-fps and its associated protein-tyrosine kinase activity and displayed
      either a factor-independent or IL-3 hypersensitive phenotype and were tumorigenic
      in syngeneic recipients. Thus, introduction of the activated v-fps gene was able
      to circumvent the requirement for exogenous growth factors by FDC-P1 cells.
      Bioassay of conditioned medium from the various clones did not detect
      hematopoietic growth factor activity and PCR analysis for IL-3 transcripts were
      negative, suggesting that growth-factor independence was achieved by a mechanism
      other than autocrine production of a growth factor. We suggest that P130gag-fps
      is acting to directly stimulate a hematopoietic growth-factor signalling pathway,
      perhaps one that normally involves the endogenous c-fps/fes protein-tyrosine
      kinase of FDC-P1 cells.

PMID- 1390903
TI  - The synthesis of p58cyclin A and the phosphorylation of p34cdc2 are inhibited in
      human lymphoid cells arrested in G1 by alpha-interferon.
AB  - Daudi cells arrest in G1 in the presence of alpha-interferon. Such cells have
      little p58cyclin A, probably due to inhibition of p58cyclin A synthesis. The
      phosphorylation-associated migration shift of p34cdc2 is not seen in alpha
      interferon-arrested cells. Cells arrested in late G1 by aphidicolin have abundant
      p58cyclin A and phosphorylated p34cdc2. Cell sorting showed that p58cyclin A
      increases in proliferating cells in late G1 and coincides with phosphorylation of
      p34cdc2.

PMID- 1390904
TI  - Photoaffinity labeling of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) on
      intact platelets with 8-azido-[gamma-32P]ATP.
AB  - The fibrinogen receptor GPIIb-IIIa plays a crucial role in platelet aggregation.
      Here we show that the adenine nucleotide, 8-azido-ATP, inhibits ADP-induced
      conformational change of the platelet fibrinogen receptor GPIIb-IIIa (integrin
      alpha IIb beta 3). Photoaffinity labeling of intact platelets with 8-azido-[gamma
      32P]ATP exclusively modifies two plasma-membrane glycoproteins which are
      identical with both subunits of GPIIb-IIIa. The presence of adenine-nucleotide
      binding sites on GPIIb-IIIa implies that the platelet fibrinogen receptor is
      directly regulated by extracellular adenine nucleotides.

PMID- 1390905
TI  - Alpha 5 integrin subunit expression changes during myogenesis.
AB  - Fibronectin and its cellular receptor, the alpha 5 beta 1 integrin, are involved
      in the transmembrane signalling events that control muscle cell differentiation.
      In this study, the expression of the alpha 5 integrin subunit was followed by
      reverse transcription-polymerase chain reaction (RT-PCR) to determine alterations
      during myogenesis. In studies of murine muscle, we found a 90% reduction in the
      level of the alpha 5 integrin subunit mRNA during early postnatal development.
      Concurrently, the fibronectin alternative splicing pattern changed markedly in
      the EIIIB and V exons. In-vitro analyses of these molecules during myoblast
      differentiation revealed changes that followed trends similar to those observed
      in vivo, although of lesser magnitude. These observations imply an important role
      of fibronectin and the alpha 5 integrin subunit in muscle development.

PMID- 1390906
TI  - Comparative investigations on the amino-acid sequences of different isolectins
      from the sponge Axinella polypoides (Schmidt).
AB  - The sponge Axinella polypoides contains four different D-galactose binding
      lectins and one, termed lectin IV, which is specific for hexuronic acids. Only
      the D-galactose binding lectins were investigated in this study. The complete
      amino-acid sequence of lectin I, the main component in the crude extract was
      determined. Lectin I is a homodimer and each subunit comprises 144 amino acids
      with a M(r) of 15,847 +/- 10, as calculated from the sequence data and determined
      by mass spectrometry. Each subunit contains one intrachain disulfide bridge
      between positions 4 and 46. Of lectin II, only the first 49 amino acids of the
      NH2-terminal end were analysed. This part has 29 amino acids in common with
      lectin I, including a cysteine residue at position 4, also suggesting an
      intrachain loop in a identical position as in lectin I. The molecular mass of its
      subunit is 16,235 +/- 10 Da. Only the first 15 NH2-terminal amino acids of
      lectins III and V could be sequenced. Lectin V was identical to lectin II in all
      positions, whereas lectin III showed only 5 residues identical to lectins I or
      II. Thus, lectins I, II and III are derived from three different genes, whereas
      lectin V may either be a proteolytic cleavage product, or result from different
      splicing events or may be derived also from a separate gene. Neither of the four
      lectins showed any similarity to known lectin sequences of animal or plant
      origin.

PMID- 1390908
TI  - Intermolecular disulfide bonds link specific high-molecular-weight glutenin
      subunits in wheat endosperm.
AB  - A detergent wash extracted soluble proteins from wheat flour, leaving a residue
      enriched with insoluble glutenin aggregates. Digestion of this residue with
      endoproteinase Lys-C, which showed a limited specificity for glutenin subunits,
      produced several peptides with apparent molecular weights close to those of
      intact high-molecular-weight glutenin subunits. N-terminal sequencing indicated
      that the isolated peptides were composed of high-molecular-weight glutenin
      subunit fragments joined by an intermolecular disulfide bond. In two of these
      peptides, only two components were found, one from an x-type subunit and the
      other from a y-type subunit. The isolated peptides all contained at least one x
      type C-terminal region and one y-type N-terminal region, suggesting a specific
      orientation to the intermolecular disulfide linkage.

PMID- 1390907
TI  - The oligomeric structure of rat liver microsomal glutathione transferase studied
      by chemical cross-linking.
AB  - The oligomeric structure of rat liver microsomal glutathione transferase was
      investigated using four different chemical cross-linking reagents. Studies were
      performed with the isolated enzyme, with the enzyme incorporated into
      phosphatidyl choline liposomes and with rat liver microsomes. Cross-linking was
      analyzed by use of SDS-PAGE combined with Western blotting. Our results strongly
      suggest that the microsomal glutathione transferase is a trimer in situ in the
      endoplasmic reticulum, as well as in the purified state and in proteoliposomes.
      These results lend strong support to previous studies, involving hydrodynamic
      characterization and radiation inactivation, indicating that the microsomal
      glutathione transferase is a trimeric enzyme.

PMID- 1390909
TI  - Heterogeneous flexibilities of the active site domains of homodimeric creatine
      kinase: effect of substrate.
AB  - (1) A single subunit and both subunits of creatine kinase from rabbit muscle was
      derivatized at the active site with the thiol-specific reagent 2-(4'
      (iodoacetamido)anilino)-naphthalene-6-sulfonic acid. (2) The highly biphasic
      kinetics of the labelling reaction were characterized from measurements of
      activity, steady-state fluorescence and anisotropy. Derivatization of one thiol
      and both thiols resulted in 48 and 100% inhibition, respectively. The dead-end
      complex (DEC), consisting of creatine, MgADP and protein, inhibited the rate, but
      not the extent, of derivatization and resulted in a 2-fold increase in
      fluorescence. (3) The fluorescence of singlylabelled (1AANS/CK) and
      doublylabelled (2AANS/CK) protein exhibited three discrete lifetime components or
      a two-term Lorentzian distribution. The decay laws for both preparations were not
      remarkably different, except that, unlike 1AANS/CK, the longer decay component of
      2AANS/CK was distributed, which narrowed in the presence of the DEC. (4) The
      steady-state anisotropies of 1AANS/CK and 2AANS/CK at 25 degrees C were 0.305 and
      0.240, respectively. It was concluded that the fast reacting site was immobile
      and the slow reacting site was flexible. Kinetics of labelling and anisotropy
      emission spectra indicated that the DEC immobilized the flexible site. (5) The
      anisotropy decay of 1AANS/CK with and without the DEC was described by a
      rotational correlation time of about 50 ns, characteristic of the molecular
      rotation of the CK dimer. At least two terms were required to fit the data for
      2AANS/CK, indicating additional segmental motion which was eliminated upon
      formation of the DEC. (6) Energy transfer from tryptophans to AANS indicated
      movement of approx. 3 A accompanying formation of the DEC.

PMID- 1390910
TI  - Biochemical properties of recombinant mutants of nonglycosylated single chain
      urokinase-type plasminogen activator.
AB  - The role of glycosylation on the enzymatic properties of single chain urokinase
      type plasminogen activator (scu-PA) was investigated by site-specific mutagenesis
      of the glycosylated Asn-302 residu to Gln. In addition, the role of the NH2
      terminal polypeptide chain and of the Cys-148 to Cys-279 interchain disulphide
      bond on the activity of non-glycosylated scu-PA was investigated. Therefore,
      variants of recombinant scu-PA (rscu-PA) were produced by transfecting Chinese
      hamster ovary cells with cDNA encoding rscu-PA N302Q (rscu-PA with Asn-302 to Gln
      mutation), rscu-PA C279A,N302Q (rscu-PA with Cys-279 to Ala and Asn-302 to Gln
      mutations) or rscu-PA del(N2-F157)C279A,N302Q (rscu-PA C279A,N302Q with deletion
      of Asn-2 through Phe-157). These mutants were purified to homogeneity from
      conditioned cell culture medium and were obtained essentially as single chain
      molecules with specific activities on fibrin plates of (mean +/- S.E.; n = 6)
      45,000 +/- 5000. IU/mg, 19,000 +/- 800 IU/mg and < or = 100 IU/mg for rscu-PA
      N302Q, rscu-PA C279A,N302Q and rscu-PA del(N2-F157)C279A,N302Q, respectively, as
      compared to 64,000 +/- 2600 IU/mg for wild-type rscu-PA obtained in the same
      expression system. Plasmin quantitatively converts rscu-PA N302Q and rscu-PA
      C279A,N302Q to amidolytically active two-chain derivatives with a specific
      activity of 56,000 IU/mg and 32,000 IU/mg, respectively, as compared to 75,000
      IU/mg for wild-type rscu-PA. Plasminogen activation as a function of time was
      comparable for rscu-PA N302Q and wild-type rscu-PA, and somewhat slower for rscu
      PA C279A,N302Q. In a human plasma milieu in vitro, consisting of a 125I-fibrin
      labeled plasma clot submerged in plasma, 50 percent clot lysis in 2 h required
      2.2 micrograms/ml rscu-PA N302Q and 6.0 micrograms/ml rscu-PA C279A,N302Q, as
      compared to 3.2 micrograms/ml wild-type rscu-PA. In contrast, rscu-PA del(N2
      F157)C279A,N302Q was not converted to an amidolytically active two chain
      derivative by plasmin, and did not induce significant plasminogen activation in
      purified systems or clot lysis in a human plasma milieu. Following bolus
      injections in hamsters, the initial half-lives (1.8-2.6 min) and the plasma
      clearances (0.6-1.5 ml min-1) were comparable for wild-type rscu-PA and for the
      three rscu-PA mutants. These results suggest that the fibrinolytic activity in a
      plasma milieu in vitro and the in vivo turnover of rscu-PA are not markedly
      affected by the absence of carbohydrate.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1390911
TI  - The lytic enzyme of the Pseudomonas phage phi 6. Purification and biochemical
      characterization.
AB  - The lytic enzyme of the lipid-containing bacteriophage phi 6, protein P5, has
      been purified to apparent homogeneity from disrupted viral particles. The enzyme
      is a monomer with a molecular mass of approx. 24 kDa. The optimal pH for P5
      activity is 8.5 and the protein is readily inactivated at temperatures above 20
      degrees C. Protein P5 is active against several Gram-negative bacteria, but no
      activity against Gram-positive species was detected. Analysis of cell wall
      digests indicates that P5 is not a glycosidase, but an endopeptidase splitting
      the peptide bridge formed by meso-diaminopimelic acid and D-alanine.

PMID- 1390912
TI  - A protein homologous to glyceraldehyde-3-phosphate dehydrogenase is induced in
      the cell wall of a flocculent Kluyveromyces marxianus.
AB  - A protein with an apparent molecular weight of 37,000 (p37) is present in very
      large amounts in the cell wall of Kluyveromyces marxianus, after the induction of
      flocculation of the yeast. This protein was isolated by preparative gel
      electrophoresis and its purity checked by SDS-PAGE and reverse-phase HPLC. SDS
      PAGE, endoglycosidase-H treatment and peptide sequencing indicated that p37 is a
      glycoprotein with a high identity to cytosolic glyceraldehyde-3-phosphate
      dehydrogenase from Saccharomyces cerevisiae. Polyclonal antibodies were used for
      Western blot analysis and immunocytochemistry, which showed that p37 is present
      in the cell wall of non-flocculent K. marxianus and, therefore, is a constitutive
      protein of the cell wall.

PMID- 1390913
TI  - Conformational analysis of a mitochondrial presequence derived from the F1-ATPase
      beta-subunit by CD and NMR spectroscopy.
AB  - Previous studies on mitochondrial targeting presequences have indicated that
      formation of an amphiphillic helix may be required for efficient targeting of the
      precursor protein into mitochondria, but the structural details are not well
      understood. We have used CD and NMR spectroscopy to characterize in detail the
      structure of a synthetic peptide corresponding to the presequence for the beta
      subunit of F1-ATPase, a mitochondrial matrix protein. Although this peptide is
      essentially unstructured in water, alpha-helix formation is induced when the
      peptide is placed in structure-promoting environments, such as SDS micelles or
      aqueous trifluoroethanol (TFE). In 50% TFE (by volume), the peptide is in dynamic
      equilibrium between random coil and alpha-helical conformations, with a
      significant population of alpha-helix throughout the entire peptide. The helix is
      somewhat more stable in the N-terminal part of the presequence (residues 4-10),
      and this result is consistent with the structure proposed previously for the
      presequence of another mitochondrial matrix protein, yeast cytochrome oxidase
      subunit IV. Addition of increasing amounts of TFE causes the alpha-helical
      content to increase even further, and the TFE titration data for the presequence
      peptide of the F1-ATPase beta-subunit are not consistent with a single,
      cooperative transition from random coil to alpha-helix. There is evidence that
      helix formation is initiated in two different regions of the peptide. This result
      helps to explain the redundancy of the targeting information contained in the
      presequence for the F1-ATPase beta-subunit.

PMID- 1390914
TI  - The predicted proteinase furin is not the hepatic proalbumin convertase.
AB  - Rat and chicken liver microsomal membranes were used to investigate the
      relationship between proalbumin processing activity and the predicted proteinase
      furin. Two polyclonal antisera directed against the predicted catalytic domain of
      furin showed the highest level of immunoreactivity in a microsomal fraction that
      had minimal proalbumin converting activity. Extracts of the fraction containing
      most converting activity lacked detectable furin. In addition, the proalbumin
      convertase was not inhibited by the anti-furin antisera. These results strongly
      suggest that furin is not responsible for the in vivo cleavage of proalbumin.

PMID- 1390915
TI  - Super helix formation of actin filaments in an in vitro motile system.
AB  - Muscle contraction results from relative sliding of actin and myosin filaments.
      However, the possibility that actin filaments twist or rotate during sliding has
      not yet been experimentally investigated. We found that a super helix of an actin
      filament is formed in an in vitro motile system. This fact suggests that an actin
      filament twists and rotates due to a torque component of a sliding force
      generated at cross-bridges.

PMID- 1390916
TI  - In vivo glycation of bovine lens crystallins.
AB  - To investigate the possible role of glycation in the aging of lens proteins, we
      used bovine lenses as a model. We studied crystallins isolated from prenatal
      bovine lenses, calf lenses and lenses from mature animals (up to 20 years old).
      The experiments show an increase in glycation levels with age in all crystallin
      fractions. Regarding the lysine content of the different crystallins, gamma
      crystallin showed relatively high levels of early glycation products. The results
      also revealed high levels of early glycation products for the HM material
      (containing mainly alpha-crystallin). In alpha-crystallin, alpha A-subunits were
      glycated to a higher extent compared with the alpha B-subunits. There is an age
      related increase in advanced glycation products, measured as specific
      fluorescence (excitation/emission wavelengths 370/440 nm), mainly present in the
      HM and alpha-crystallin fraction.

PMID- 1390917
TI  - Primary structure of guinea-pig Hageman factor: sequence around the cleavage site
      differs from the human molecule.
AB  - The guinea-pig and human Hageman factors differ in their sensitivity to
      activation by particular bacterial proteinases. To understand this difference,
      the primary structure and cleavage site on activation of the guinea-pig molecule
      were determined and compared with the human molecule. By the use of a synthetic
      oligodeoxyribonucleotide probe which encoded a part of human Hageman factor cDNA,
      a cDNA clone was isolated from a lambda gt11 cDNA library of guinea-pig liver and
      sequenced. The cDNA clone was identified as that of guinea-pig Hageman factor by
      the complete identity of the deduced amino-acid sequence with the actual sequence
      of the amino-terminal portion of guinea-pig Hageman factor molecule and the
      active form. The cDNA included part of a leader sequence and the entire coding
      region of the Hageman factor molecule. Guinea-pig Hageman factor was composed of
      the same domain structures as the human counterpart with an overall 72% homology
      in the amino-acid sequence. However, the sequences around the cleavage site were
      surprisingly different; -Met351-Thr-Arg-Val-Val-Gly-Gly-Leu-Val359-(human) and 
      Leu338-Ser-Arg-Ile-Val-Gly-Gly-Leu-Val346-(guinea-pig). The amino-acid
      substitutions around the cleavage site might explain the difference in
      sensitivity to activation between the human and guinea-pig molecules.

PMID- 1390918
TI  - Absorbance spectral change of the cytochrome P-450S21-phenylisocyanide complex
      upon binding of reduced NADPH-cytochrome-P-450 reductase.
AB  - Reduction of cytochrome P-450S21 (SF) (SF, substrate-free; purified from bovine
      adrenocortical microsomes) with sodium dithionite (Na2S2O4) in the presence of
      phenylisocyanide produced a ferrous cytochrome P-450S21 (SF)-phenylisocyanide
      complex with Soret absorbance maxima at 429 and 456 nm. On the other hand, when a
      preformed ferric cytochrome P-450S21 (SF)-NADPH-cytochrome-P-450 reductase (Fp2)
      complex was reduced chemically or enzymatically under the same conditions, the
      absorbance spectrum of the ferrous cytochrome P-450S21 (SF)-phenylisocyanide
      complex changed drastically, as characterized by an increase in absorbance
      intensity at 429 nm and a decrease at 456 nm. Similar spectral changes were
      observed by addition of reduced Fp2 to the preformed ferrous cytochrome P-450S21
      (SF)-phenylisocyanide complex. Experiments to reduce a ferric cytochrome P-450S21
      (SF)-phenylisocyanide complex with sodium dithionite in the presence of various
      amounts of Fp2 showed that; (1), the spectral change reached maxima for both
      absorption increase at 429 nm and decrease at 456 nm when cytochrome P-450S21 and
      Fp2 were previously mixed at the cytochrome P-450S21:Fp2 ratio of 1:5; (2), the
      spectral change was suppressed in 300 mM potassium phosphate buffer (pH 7.4).
      These results suggest that the absorbance spectral change is due to a
      conformational change around the heme moiety induced by association with reduced
      Fp2.

PMID- 1390919
TI  - Thermodynamic analysis of heparin binding to human antithrombin.
AB  - The binding of heparin to human antithrombin III (ATIII) was investigated by
      titration calorimetry (TC) and differential scanning calorimetry (DSC). TC
      measurements of homogeneous high-affinity pentasaccharide and octasaccharide
      fragments of heparin in 0.02 M phosphate buffer and 0.15 M sodium chloride (pH
      7.3) yielded binding constants of (7.1 +/- 1.3) x 10(5) M-1 and (6.7 +/- 1.2) x
      10(6) M-1, respectively, and corresponding binding enthalpies of -48.3 +/- 0.7
      and -54.4 +/- 5.4 kJ mol-1. The binding enthalpy of heparin in phosphate buffer
      (0.02 M, 0.15 M NaCl, pH 7.3) was estimated from TC measurements to be -55 +/- 10
      kJ mol-1, while the enthalpy in Tris buffer (0.02 M, 0.15 M NaCl, pH 7.3) was -18
      +/- 2 kJ mol-1. The heparin-binding affinity was shown by fluorescence
      measurements not to change under these conditions. The 3-fold lower binding
      enthalpy in Tris can be attributed to the transfer of a proton from the buffer to
      the heparin-ATIII complex. DSC measurements of the ATIII unfolding transition
      exhibited a sharp denaturation peak at 329 +/- 1 K with a van 't Hoff enthalpy of
      951 +/- 89 kJ mol-1, based on a two-state transition model and a much broader
      transition from 333 to 366 K. The transition peak at 329 K accounted for 9-18% of
      the total ATIII. At sub-saturate heparin concentrations, the lower temperature
      peak became bimodal with the appearance of a second transition peak at 336 K. At
      saturate heparin concentration only the 336 K peak was observed. This supports a
      two domain model of ATIII folding in which the lower stability domain (329 K)
      binds and is stabilized by heparin.

PMID- 1390920
TI  - Calcium dependent conformational changes of surfactant protein A (SP-A) and its
      collagenase resistant fragment with or without dithiothreitol.
AB  - Calcium-dependent conformational changes of surfactant protein A (SP-A) and the
      collagenase resistant fragment (CRF) of SP-A were studied by measuring
      fluorescence spectra. The emission peaks of both SP-A and CRF in the absence of
      Ca2+ appeared at 343 nm when they were excited at 280 nm. In the presence of
      Ca2+, the peaks appeared at 340 nm and were accompanied by an increase in the
      fluorescence intensity. The magnitude of the fluorescence intensity change
      induced by Ca2+ was amplified by the addition of dithiothreitol (DTT) in both SP
      A and CRF. The Ca2+ binding of CRF was measured by a flow dialysis method with
      45CaCl2 in the Ca2+ concentration range where the Ca(2+)-induced fluorescence
      changes occurred. The maximum binding number of Ca2+ to CRF was about 2 mol per
      mol of CRF, and the value was independent of the presence of DTT.

PMID- 1390921
TI  - The compact domain conformation of human Glu-plasminogen in solution.
AB  - A complete understanding of the accelerating mechanisms of plasminogen activation
      and fibrinolysis necessarily requires structural information on the
      conformational forms of plasminogen. Given the absence of high-resolution
      structural data on plasminogen the use of lower resolution approaches has been
      adopted. Two such approaches have previously indicated a compact conformation of
      Glu-plasminogen (Tranqui, L., Prandini, M., and Chapel, A. (1979) Biol.
      Cellulaire, 34, 39-42; Banyai, L. and Patthy, L. (1985) Biochim. Biophys. Acta,
      832, 224-227) whereas a third has suggested a fairly extended conformation
      (Mangel, W., Lin, B. and Ramakrishnan, V. (1990) Science, 248, 69-73). Native Glu
      plasminogen has been investigated using small-angle X-ray scattering (SAXS)
      experiments. It is concluded that this molecule in solution is compact (radius of
      gyration, RG 3.05 +/- 0.02 nm and maximum intramolecular distance, Im 9.1 +/- 0.3
      nm) and that the data are consistent with the right-handed spiral structure
      observed using electron microscopy by Tranqui et al. (1979). A spiral structure
      of native plasminogen would have important implications for the conformational
      response of plasminogen to fibrin and concomitant stimulation of plasminogen
      activation.

PMID- 1390922
TI  - Purification and characterization of a low M(r) GTP-binding protein, ram p25,
      expressed by baculovirus expression system.
AB  - The ram gene was isolated from rat megakaryocyte cDNA library with an
      oligonucleotide probe which is specific for a low M(r) GTP-binding proteins c25KG
      purified from human platelets. Its gene product (ram p25) is a monomeric 25-kDa
      guanine nucleotide-binding protein. The protein was expressed by using
      baculovirus transfer vector, pAcYM1, which allowed the production at a high level
      of soluble recombinant ram p25 in Spodoptera frugiperda (Sf9) cells under the
      control of polyhedrin promoter. The expressed protein in cytosol of Sf9 cells was
      purified to near homogeneity by a combination of DEAE-Toyopearl 650(S) and
      hydroxyapatite HCA-100S column chromatography. The purified ram p25 bound approx.
      0.8 +/- 0.02 mol of guanosine 5'-O-1-thiotriphosphate (GTP gamma S)/mol of
      protein with a Kd value of 340 +/- 4.91 nM in a reaction mixture containing 10
      microM of free magnesium ions. In the presence of 5 mM Mg2+, [3H]GDP was
      dissociated from ram p25 at the rate of 0.015 +/- 0.0010 min-1 and the
      dissociation was greatly enhanced by addition of 250 mM (NH4)2SO4. The rate of
      [gamma-32P]GTP-hydrolysis for ram p25 was 0.010 +/- 0.0012 min-1. Thus, it was
      indicated that the GTP-hydrolysis reaction is a rate-limiting step in the guanine
      nucleotide turnover of ram p25. ram p25 shares 23 and 80% amino-acid homology
      with the Ha-ras p21 and c25KG protein, respectively, and is similar to them in
      GTP gamma S binding activity in a time- and dose-dependent manner. But it differs
      from ras p21 in the rate-limiting step of the guanine nucleotide turnover.

PMID- 1390923
TI  - Barley malt-alpha-amylase. Purification, action pattern, and subsite mapping of
      isozyme 1 and two members of the isozyme 2 subfamily using p-nitrophenylated
      maltooligosaccharide substrates.
AB  - Isoforms AMY1, AMY2-1 and AMY2-2 of barley alpha-amylase were purified from malt.
      AMY2-1 and AMY2-2 are both susceptible to barley alpha-amylase/subtilisin
      inhibitor. The action of these isoforms is compared using substrates ranging from
      p-nitrophenylmaltoside through p-nitrophenylmaltoheptaoside. The kcat/Km values
      are calculated from the substrate consumption. The relative cleavage frequency of
      different substrate bonds is given by the product distribution. AMY2-1 is 3-8
      fold more active than AMY1 toward p-nitrophenylmaltotrioside through p
      nitrophenylmaltopentaoside. AMY2-2 is 10-50% more active than AMY2-1. The
      individual subsite affinities are obtained from these data. The resulting subsite
      maps of the isoforms are quite similar. They comprise four and six glucosyl
      binding subsites towards the reducing and the non-reducing end, respectively.
      Towards the non-reducing end, the sixth and second subsites have a high affinity,
      the third has very low or even lack of affinity and the first (catalytic subsite)
      has a large negative affinity. The affinity declines from moderate to low for
      subsites 1 through 4 toward the reducing end. AMY1 has clearly a more negative
      affinity at the catalytic subsite, but larger affinities at both the fourth
      subsites, compared to AMY2. AMY2-1 has lower affinity than AMY2-2 at subsites
      adjacent to the catalytic site, and otherwise mostly higher affinities than AMY2
      2. Theoretical kcat/Km values show excellent agreement with experimental values.

PMID- 1390925
TI  - Mechanism of ligand-protein interaction in plant seed thiamin-binding proteins.
      Probing the binding site of protein isolated from buckwheat seeds with a series
      of thiamin-related compounds.
AB  - Affinities of 14 thiamin derivatives or antagonists to a thiamin-binding protein
      isolated from buckwheat seeds were determined. A competitive displacement of
      radiolabeled thiamin by unlabeled ligand was analysed by a computerized model
      fitting procedure. The dissociation constant of the thiamin-protein complex was
      0.93 microM. Most modifications in ligand chemical structure weakened the ligand
      protein interaction. A model of the thiamin-binding site is suggested. The
      hydroxyethyl-chain of thiamin while protein-bound appears to be excluded from the
      binding region. A positively charged quaternary nitrogen atom of the thiazolium
      ring probably interacts with some negative group(s) of protein. The rest of the
      thiazolium ring as well as the amino group of the pyrimidine fragment serve as
      additional anchors. The three structural features of the thiamin molecule
      accounting for binding contribute equally to overall binding energy by about 11
      12 kJ/mol.

PMID- 1390926
TI  - Allosteric properties of haemoglobin beta 41 (C7) Phe-->Tyr: a stable, low-oxygen
      affinity variant synthesized in Escherichia coli.
AB  - In human deoxy haemoglobin, the alpha 42(C7)Tyr-residue is hydrogen-bonded to
      beta 99(G1)Asp which stabilizes the low-oxygen-affinity deoxy conformation. We
      engineered a haemoglobin with Tyr for Phe at the homologous C7 position in beta
      chains. The oxygen affinity of the variant is decreased about two-fold relative
      to Hb A while keeping similar KR and KT values. This mutant may be a candidate
      for the development of an artificial oxygen carrier, as it would not require an
      external effector for significant oxygen unloading in vivo.

PMID- 1390924
TI  - Caution: the glycylmethyl and glycylethyl esters of glutathione are substrates
      for glyoxalase I.
AB  - The glycylmethyl and glycylethyl esters of glutathione have been synthesized and
      carefully characterized by both 1H-NMR and tandem FAB mass spectrometry. Contrary
      to previously published studies, these compounds (as their methylglyoxal
      thiohemiacetals) do indeed serve as moderately efficient substrates for yeast
      glyoxalase I, with kcat values that are approx. 3-fold smaller and Km values that
      are approx. 3-fold larger than those of the thiohemiacetal formed from
      glutathione. Product inhibition studies show that the glycylmethyl and
      glycylethyl esters of (S)-D-lactoylglutathione bind approx. 1.4-fold less tightly
      to the active site than (S)-D-lactoylglutathione. These observations exclude an
      essential role for the glycyl-CO2- of substrate in active site binding and
      catalysis.

PMID- 1390927
TI  - Pressure-induced conformational changes in an antigen and an antibody and the
      implications on their use for hyperbaric immunoadsorption.
AB  - Pressure-induced conformational changes in two proteins, bovine serum albumin
      (BSA) and immunoglobulin G (IgG), were studied to assess the application of
      hyperbaric manipulation to the dissociation of antigen-antibody complexes.
      Antigen-antibody dissociation is important in the product-recovery phase of
      immunoadsorption, an affinity purification process. Three techniques were used in
      parallel for this study, including fluorescence, Fourier transform infrared
      (FTIR) spectroscopy, and the enzyme-linked immunosorbent assay (ELISA). Employing
      a fluorescent probe, fluorescent intensity measurements were used to detect
      protein conformational changes. FTIR spectroscopy was used to determine changes
      in protein secondary structure induced by high pressure, while the ELISA test was
      used to examine antibody recognition after the proteins had been pressure
      treated. The results from this work demonstrate that IgG is resistant to
      conformational changes induced by pressures below 2 kbar. In contrast, BSA
      undergoes reversible conformational changes in this pressure range. However,
      these conformational changes are not reflected in tests measuring antibody
      recognition. These findings indicate that IgGs have the potential to be used as
      recycled ligands in immunoadsorption separation processes. Different antigens
      that are being considered for purification by immunoadsorption and separated by
      means of high pressure could be screened by the methods disclosed to determine
      their stability under high pressure conditions.

PMID- 1390928
TI  - FTIR spectroscopic kinetic analysis of alkaline phosphatase under hyperbaric
      manipulation.
AB  - For the first time, high-pressure infrared spectroscopy has been used in an
      enzyme kinetics study. This technique allows not only the investigation of
      kinetics under very high pressure, but it also allows simultaneous determinion of
      changes in the secondary structure of enzymes at the corresponding pressures. In
      the present study, a classical enzyme reaction, the conversion of p-nitrophenol
      phosphate into p-nitrophenol by alkaline phosphatase was selected to demonstrate
      the potential of infrared spectroscopy as an alternative physical method in the
      high-pressure study of enzyme kinetics. The rate constants of this enzyme
      reaction have been determined as a function of pressure in the pressure range
      0.001-14 kbar. The first-order rate constants thus obtained increases with
      increasing pressure up to 8.3 kbar. At this pressure, the reaction rate decreases
      abruptly due to the denaturation of the enzyme arising from the conformational
      changes of some alpha-helical segments in the enzyme molecules into beta-sheet
      structure. The present results suggest that the pressure-enhanced overall
      hydrogen-bond strength in the amide groups of the enzyme is one of the factors
      which stimulate the enzyme activity. Moreover, the dissociation of the dimeric
      enzyme into its subunits does not inhibit the enzyme activity but only attributes
      to a slight change in activation volume.

PMID- 1390929
TI  - Components and proteolytic processing sites of arylsulfatase B from human
      placenta.
AB  - Previous studies have shown that mature arylsulfatase B purified from human
      sources is composed of two non-identical chains with apparent molecular masses of
      43 kDa and 8 kDa. Arylsulfatase B purified from human placenta in the present
      study, however, included another 7 kDa component that could be detected only by
      carbohydrate staining on reducing SDS-PAGE employing the Tris-Tricine system. The
      43 kDa and 7 kDa components contained a carbohydrate moiety, but the 8 kDa one
      did not, as demonstrated by periodic acid-Schiff staining, Con-A lectin blotting,
      endo-glycosidase treatment and in vitro phosphorylation by UDP-N
      acetylglucosamine: lysosomal enzyme N-acetylglucosamine 1-phosphotransferase. The
      purified arylsulfatase B migrated as a single polypeptide of 58 kDa on non
      reducing SDS-PAGE, indicating that the three chains are linked by disulfide
      bonds. In order to determine the origin of the components, N-terminal sequencing
      of the isolated polypeptides was performed. As a result, the 43, 7 and 8 kDa
      components were found to commence with Ala-41, Ala-424 and Asp-466, respectively.
      These results suggest that after removal of the signal peptide, human
      arylsulfatase B undergoes proteolytic processing on at least two sites during
      maturation.

PMID- 1390930
TI  - Chemical modification of arginine residues in alpha-bungarotoxin.
AB  - The reaction of alpha-bungarotoxin (alpha-BuTX) with 1,2-cyclohexanedione
      resulted in the modification of only Arg-72 but arginine at position 36 or 72, as
      well as both were modified by reaction of the toxin with p-hydroxyphenylglyoxal.
      No derivative modified at Arg-25 was obtained, indicating that this residue may
      be located in the interior region of alpha-BuTX molecule. Monoderivative at Arg
      72 showed about 50% of the lethal toxicity and binding activity of alpha-BuTX to
      nicotinic acetylcholine receptor (AChR), while the activity was decreased to one
      third when the invariant Arg-36 was modified, indicating that the latter residue
      is more closely related to the interaction of the toxin with AChR. Approx. 13% of
      the residual activity was observed when both arginine residues at 36 and 72 were
      modified. The antigenicity of alpha-BuTX was still retained essentially intact
      after Arg-36 or -72 was modified, whereas it decreased to 50% when both these
      arginine residues were modified. The present study indicates that Arg-36 and -72
      in alpha-BuTX may be involved in the multipoint contact between the toxin and
      AChR, but neither is absolutely essential for the binding.

PMID- 1390931
TI  - Subunits asymmetry in the ternary complex of lamb liver 6-phosphogluconate
      dehydrogenase detected by a NADP analogue.
AB  - Incubation of lamb liver 6-phosphogluconate dehydrogenase, a dimeric enzyme with
      periodate-oxidized NADP causes the inactivation of the enzyme due to the covalent
      binding of 2 mol of inhibitor/mol of dimer. In the presence of substrate, the
      inactivation is faster and is almost complete after the labelling of only one
      subunit. These results not only confirm the hypothesis of a 'half-of-the-sites'
      mechanism of action of the enzyme, but also suggest that the formation of the
      ternary complex (enzyme-substrate-coenzyme) in one subunit causes a
      conformational change that makes the other subunit unable to bind the coenzyme
      (and even the adenylic part of it) and, thus, this subunit becomes inactive. It
      appears that while one subunit catalyses the oxidation of 6-phosphogluconate the
      other is inactive in this reaction.

PMID- 1390932
TI  - Nucleotide- and temperature-induced changes in myosin subfragment-1 structure.
AB  - The effects of nucleotide binding and temperature on the internal structural
      dynamics of myosin subfragment 1 (S1) were monitored by intrinsic tryptophan
      phosphorescence lifetime and fluorescence anisotropy measurements. Changes in the
      global conformation of S1 were monitored by measuring its rate of rotational
      diffusion using transient electric birefringence techniques. At 5 degrees C, the
      binding of MgADP, MgADP,P and MgADP,V (vanadate) progressively reduce the
      rotational freedom of S1 tryptophans, producing what appear to be increasingly
      more rigidified S1-nucleotide structures. The changes in the luminescence
      properties of the tryptophans suggest that at least one is located at the
      interface of two S1 subdomains. Increasing the temperature from 0 to 25 degrees C
      increases the apparent internal mobility of S1 tryptophans in all cases and, in
      addition, a reversible temperature-dependent transition centered near 15 degrees
      C was observed for S1, S1-MgADP and S1-MgADP,P, but not for S1-MgADP,V. The
      rotational diffusion constants of S1 and S1-MgADP were measured at temperatures
      between 0 and 25 degrees C. After adjusting for the temperature and viscosity of
      the solvent, the data indicate that the thermally induced transition at 15
      degrees C comprises local conformational changes, but no global conformational
      change. Structural features of S1-MgADP,P, which may relate to its role in force
      generation while bound to actin, are presented.

PMID- 1390933
TI  - Lactoperoxidase-catalyzed oxidation of thiocyanate ion: a carbon-13 nuclear
      magnetic resonance study of the oxidation products.
AB  - Products formed from the lactoperoxidase (LPO) catalyzed oxidation of thiocyanate
      ion (SCN-) with hydrogen peroxide (H2O2) have been studied by 13C-NMR at pH 6 and
      pH 7. Ultimate formation of hypothiocyanite ion (OSCN-) as the major product
      correlates well with the known optical studies. The oxidation rate of SCN-
      appears to be greater at pH < or = 6.0. At [H2O2]/[SCN-] ratios of < or = 0.5,
      OSCN- is not formed immediately, but an unidentified intermediate is produced. At
      [H2O2]/[SCN-] > 0.5, SCN- appears to be directly oxidized to OSCN-. Once formed,
      OSCN- slowly degrades over a period of days to carbon dioxide (CO2), bicarbonate
      ion (HCO3-), and hydrogen cyanide (HCN). An additional, previously unrecognized
      product also appears after formation of OSCN-. On the basis of carbon-13 chemical
      shift information this new species is suggested to result from rearrangement of
      OSCN- to yield the thiooxime isomer, SCNO- or SCNOH.

PMID- 1390934
TI  - Long range electron transfer along an alpha-helix.
AB  - The many observations of long range electron transfer in proteins raises the
      question of whether a protein's structure can influence the rate or path of such
      transfers, and if so, then how. To answer these questions requires information on
      which of the various structural elements composing proteins support long range
      electron transfer. In this report, we present evidence for long range electron
      transfer along the alpha-helix of a synthetic leucine zipper dimer. We also
      present electron transfer rate data obtained with other helical peptides.

PMID- 1390935
TI  - Soman inhibition of butyrylcholinesterase in the presence of substrate: pressure
      and temperature perturbations.
AB  - Irreversible inhibition of butyrylcholinesterase by soman was studied in the
      presence of the substrate (o-nitrophenyl butyrate). Inhibition was found of the
      competitive complexing type. Study at different temperatures and pressures showed
      that the behavior of the enzyme differs from that of the inhibitor-free enzyme.
      In the absence of inhibitor, enzyme kinetics displayed a non-linear temperature
      dependence with a break at 21 degrees C. In the presence of a non-inhibitor
      structural analog of soman (pinacolyl dimethylphosphinate and methyl
      dimethylphosphinate), the Arrhenius plot break is slightly shifted (18 degrees
      C). On the other hand, in the presence of soman this break is abolished. The
      pressure-dependence of the substrate hydrolysis revealed also differences between
      the native enzyme and the enzyme in the presence of soman: the sign and magnitude
      of the apparent activation volume (delta V not equal to) were different for the
      two reactions. Beyond 300 bar, in the presence of soman, a plateau (delta V not
      equal to approx. 0) was observed over a large pressure range depending on
      temperature. Such a behavior with respect to temperature and pressure can reflect
      a soman-induced enzyme conformational state. Thus, temperature and pressure
      perturbations of the kinetics allow to complete the inhibition scheme of
      butyrylcholinesterase by soman. Our data suggest that upon soman binding, the
      enzyme undergoes a long-lived soman-induced-fit conformational change preceding
      the phosphonylation step. However, an alternative hypothesis according to which
      the enzyme processes a secondary soman-binding site cannot be ruled out.

PMID- 1390936
TI  - Ionizable groups linked to the reaction of 2,2'-dithiobispyridine with
      hemoglobin.
AB  - The pH-dependence of the second-order rate-constant for the reaction of 2,2'
      dithiobispyridine with the CysF9(93) beta sulphydryl group of hemoglobin in the R
      quaternary structure is analyzed in terms of a tentative model based on the
      observation that this sulphydryl exists as a mixture of two tertiary
      conformations in dynamic equilibrium. For the four aquomethemoglobins studied
      (human A and S, dog and rabbit), the equation derived from this model gives a
      better fit than a simpler equation based on the assumption of only one tertiary
      conformation. For the corresponding carbonmonoxyhemoglobins the simpler equation
      gives a better fit. The dog and rabbit oxy and azidomet data are better fitted by
      the model equation, whereas the data for the corresponding human A and S
      derivatives are better fitted by the simpler equation. From the analysis pKa
      values of 6.1 and 8.7 are obtained for the ionization of groups coupled to the
      presumed conformational transition. The pKa of 6.1 is assigned to HisHC3(146)
      beta; the pKa of 8.7 is assigned to the CysF9(93) beta sulphydryl group in its
      external conformation. It is estimated that the pKa of this sulphydryl may be as
      high as 12.9 in its internal conformation.

PMID- 1390937
TI  - Clusterin binds by a multivalent mechanism to the Fc and Fab regions of IgG.
AB  - Clusterin was purified from human serum by IgG and monoclonal antibody affinity
      chromatography. SDS-PAGE and immunoblotting revealed no major differences between
      clusterin prepared in these two ways. An ELISA method for measuring the binding
      of clusterin to immunoglobulins was developed. Clusterin purified by IgG affinity
      chromatography bound to pooled human IgG with a similar affinity (S0.5 5.9 +/-
      0.4 micrograms/ml) as clusterin purified by monoclonal antibody chromatography
      (S0.5 6.1 +/- 0.2 micrograms/ml). The apparent affinity of clusterin for IgG
      immobilised on ELISA plates increased with increasing concentrations of IgG in
      the coating solution. Aggregated IgG in solution was a more potent inhibitor of
      the binding of clusterin to immobilised IgG than was monomer IgG. Clusterin bound
      to all of the isotypes of human IgG, and to human IgA and IgM, with apparent
      affinities in the order IgG3 > IgG4 > IgM > IgG1 > IgG2, IgA. Clusterin bound to
      both the Fab and Fc fragments of human IgG. The clusterin binding site(s) on the
      Fc do not overlap with those for protein A and Clq.

PMID- 1390939
TI  - Albumin Rugby Park: a truncated albumin variant caused by a G-->C splice-site
      mutation in intron 13.
AB  - Three members of a family were found to be heterozygous for a fast albumin
      variant (Albumin Rugby Park) that made up only 8% of total serum albumin.
      Isoelectric focussing indicated an increased negative charge on the C-terminal
      CNBr peptide and C-terminal sequence analysis of the native protein showed an
      aberrant sequence of -Ser-Phe. Sequence analysis of PCR-amplified DNA indicated a
      G-->C mutation at position 1 of the 13th intron and this was confirmed by
      restriction digestion. The replacement of the obligate GT sequence by CT at the
      exon/intron boundary prevents splicing of the 13th intron and translation
      continues for 21 nucleotides until a stop codon is reached. The new protein lacks
      the 14 amino acids coded for in the 14th exon (GKKLVAASQAALGH), but these are
      replaced by 7 new residues (LLQFSSF), giving a truncated albumin of 578 residues.

PMID- 1390938
TI  - Platelet procoagulant activity and microvesicle formation. Its putative role in
      hemostasis and thrombosis.

PMID- 1390940
TI  - Hemoglobin Dallas (alpha 97(G4)Asn-->Lys): functional characterization of a high
      oxygen affinity natural mutant.
AB  - Hemoglobin Dallas, an alpha-chain variant with a substitution of lysine for
      asparagine at position 97(G4), was found to have increased oxygen affinity (p1/2
      = 1 mmHg at pH 7.3 and 20 degrees C), diminished cooperativity (n, the Hill
      coefficient = 1.7) and reduced Bohr effect (about 50%). Addition of allosteric
      effectors (such as 2,3-diphosphoglycerate, inositol hexakisphosphate and
      bezafibrate) led to a decrease in oxygen affinity and increase in cooperative
      energy. Kinetic studies at pH 7.0 and 20 degrees C revealed that (i), the overall
      rate of oxygen dissociation is 1.4-fold slower than that for HbA and (ii), the
      carbon monoxide dissociation rate is unaffected. The abnormal properties of this
      hemoglobin variant can be attributed to a more 'relaxed' T-state.

PMID- 1390941
TI  - A new, simple assay for long-chain acyl-CoA dehydrogenase in cultured skin
      fibroblasts using stable isotopes and GC-MS.
AB  - In this paper, we present a new method for measurement of long-chain acyl-CoA
      dehydrogenase (LCAD) activities in cultured skin fibroblasts. The method is based
      upon gas chromatographic/mass spectrometric determination of 3-OH-hexadecanoic
      acid formed during incubation of fibroblasts in a medium containing palmitoyl-CoA
      and crotonase, to convert the enoyl-CoA ester produced into the 3-hydroxyacyl-CoA
      ester. The validity of the method is demonstrated by the finding of a full
      deficiency of LCAD in fibroblasts from three patients with an established
      deficiency of LCAD.

PMID- 1390943
TI  - A guinea-pig hereditary cataract contains a splice-site deletion in a crystallin
      gene.
AB  - A congenital cataract present in guinea pigs provided a unique opportunity to
      study a hereditary lens disease at the molecular level. zeta-Crystallin, one of
      the most abundant guinea pig lens proteins, was found to be altered in the lens
      of cataractous animals. Several zeta-crystallin cDNA clones were isolated from a
      cataractous lens library and found to contain a 102-bp deletion towards the 3'
      end of the coding region. This deletion does not interfere with the reading frame
      but results in a protein 34 amino acids shorter. Sequence analysis of a normal
      genomic zeta-crystallin clone revealed that the missing 102-bp fragment
      corresponds to an entire exon (exon 7). PCR analysis of the genomic DNA isolated
      from cataractous animals showed that exon 7, though missing from the mRNA, is
      intact in the cataractous genome. Further sequence analysis of the zeta
      crystallin gene disclosed a dinucleotide deletion of the universal AG at the
      acceptor splice-site of intron 6 of the mutant gene. The presence of this
      mutation results in the skipping of exon 7 during the mRNA processing which in
      turn results in the altered zeta-crystallin protein. This is the first time a
      genomic mutation in an enzyme/crystallin gene has been directly linked to a
      congenital cataract.

PMID- 1390942
TI  - The blood group B type-4 heptaglycosylceramide is a minor blood group B structure
      in human B kidneys in contrast to the corresponding A type-4 compound in A
      kidneys. Structural and in vitro biosynthetic studies.
AB  - Blood group A glycolipid antigens have been found based upon at least four
      different core saccharides (types 1 to 4). The biological significance of this
      structural polymorphism is not known, although the successful outcome of
      transplantations of blood group A2 kidneys to blood group O individuals have been
      partly explained by the low expression of A type-3 and -4 chain glycolipid
      antigens in A2 kidneys. If graft rejection due to ABO incompatibility is, in any
      way, correlated to the expression of type-3 and -4 chain blood group glycolipids,
      it is of interest to identify possible blood group B structures based on these
      core saccharides. In a non-acid glycosphingolipid fraction isolated from human
      blood group B kidneys, mass spectrometry, high-temperature gas chromatography
      mass spectrometry and probing of thin-layer chromatograms with Gal alpha 1-4Gal
      specific Escherichia coli and monoclonal anti-B antibodies provided evidence for
      minute amounts of a Gal alpha 1-3(Fuc alpha 1-2)Gal beta-HexNAc-Gal alpha 1-4Gal
      beta-Hex-Ceramide structure consistent with a B type-4 chain
      heptaglycosylceramide. In contrast, blood group A kidneys have the corresponding
      A type-4 chain heptaglycosylceramide as the predominant blood group A glycolipid.
      No, or very low activity of the blood group B gene enzyme on the type-4 chain
      blood group H hexaglycosylceramide precursor was found by biosynthetic
      experiments in vitro, which might explain the low expression of type-4 chain
      blood group B heptaglycosylceramides in human blood group B kidneys.

PMID- 1390944
TI  - Hemoglobin Rouen (alpha-140 (HC2) Tyr-->His): alteration of the alpha-chain C
      terminal region and moderate increase in oxygen affinity.
AB  - Hb Rouen (alpha 140(HC2) Tyr-->His) is a moderately high oxygen-affinity variant
      that was found in coincidence with polycythemia vera in a French patient. This
      hemoglobin provides an example of an alteration of the C-terminus of the alpha
      chain, a region involved in the mechanisms of allosteric regulation. The increase
      in oxygen-affinity and decrease in cooperativity of this variant is much smaller
      than that resulting from the same substitution in the beta-chain. This model
      provides additional evidence for the inequivalence between the alpha- and beta
      subunits.

PMID- 1390945
TI  - Immunochemical characterisation of parathyroid hormone-related protein from
      tumour and non-tumour cells.
AB  - The molecular forms of parathyroid hormone-related protein (PTHRP) in conditioned
      media from the BEN human lung cancer cell line, rat parathyroid cells (PT-r) and
      human keratinocytes were studied by gel-filtration chromatography with assay of
      PTHRP by immunoassays and bioassay. Immunoreactivity (1-86 and 1-34) and
      bioactivity (1-34) in conditioned media eluted as a coincident major peak
      (approx. molecular mass 19-22 kDa) and there was evidence of amino-terminal
      species in the molecular mass range 10-16 kDa in BEN and keratinocyte media.
      Western blotting of PTHRP affinity purified by monoclonal antibodies directed at
      regions 1-34 or 37-67, identified a major species in all cell cytosols and media
      with an apparent molecular mass of 24-25 kDa, consistently slightly larger than
      recombinant PTHRP(1-141) (mobility of 21 kDa) which may represent an intact or
      native form of PTHRP. Additional amino-terminal species were identified in medium
      from keratinocytes (16 and 7 kDa), BEN cells (18 and 14 kDa) and PT-R cells (17
      kDa), suggesting that processing occurs at the C-terminus and within the mid
      region to form a range of amino-terminal fragments.

PMID- 1390946
TI  - Active metabolism of arachidonic acid by Kaposi sarcoma cells cultured from lung
      biopsies (KS-3); identification by HPLC and MS/MS of the predominant metabolite
      secreted as the 11,12-epoxy-eicosatrienoic acid.
AB  - The development of long-term culture of AIDS-KS cells has allowed us to
      investigate further a possible vascular origin of Kaposi sarcoma. Taking into
      account the relative specificity of arachidonic acid (AA) metabolism according to
      cell type, the AA 'cascade' was analyzed in cultured KS-3 cells established from
      lung biopsies and compared to human umbilical venous endothelial (H-UVE) cells
      and human myometrial smooth muscle (H-MSM) cells, under basal conditions and
      after stimulation with vasoactive agents such as histamine or thrombin.
      Considering strictly the 'prostaglandin' profile given by RIAs, the metabolism of
      AA was closer, whilst not identical, to H-UVE than to H-MSM cells. However,
      evaluation of all the eicosanoids released from [3H]AA labeled KS-3 cells
      revealed that the predominant metabolite was not prostacyclin (PGI2), as
      suggested from PG RIAs, but an epoxy-eicosatrienoic acid (EET), identified as the
      11, 12 isomer by HPLC and MS/MS. The synthesis of this EET is probably cytochrome
      P-450 monooxygenase dependent. Its potential role in the development of the KS
      tumor cells is under investigation.

PMID- 1390947
TI  - Aurothioglucose inhibits induced NF-kB and AP-1 activity by acting as an IL-1
      functional antagonist.
AB  - We have designed a series of recombinant CAT genes to study IL-1 signal
      transduction in murine fibroblast NIH 3T3 cells. We demonstrate that the HSV
      thymidine kinase (tk) promoter does not respond to IL-1, but that IL-1 induction
      of this promoter is observed after insertion of either NF-kB or AP-1 binding
      sites upstream of the HSV tk cap-site. We have studied the effects of
      indomethacin, dexamethasone and aurothioglucose (which have been used in the
      treatment of patients affected by rheumatoid arthritis) in the IL-1 inducible CAT
      assay. We show that aurothioglucose or dexamethasone is able to inhibit IL-1
      induced CAT activity whereas a non-steroidal anti-inflammatory drug
      (indomethacin) is inactive. Order of addition experiments indicate that
      aurothioglucose, which has disease-modifying activity in treated patients, acts
      as an IL-1 functional antagonist in this system.

PMID- 1390948
TI  - Characterization of two HEXB gene mutations in Argentinean patients with Sandhoff
      disease.
AB  - Beta-hexosaminidase A (beta-N-acetyl-D-hexosaminidase, EC 3.2.1.5.2) is a
      lysosomal hydrolase composed of an alpha- and a beta-subunit. It is responsible
      for the degradation of GM2 ganglioside. Mutations in the HEXB gene encoded beta
      subunit cause a form of GM2 gangliosidosis known as Sandhoff disease. Although
      this is a rare disease in the general population, several geographically isolated
      groups have a high carrier frequency. Most notably, a 1 in 16-29 carrier
      frequency has been reported for an Argentinean population living in an area
      contained within a 375-km radius from Cordoba. Analysis of the genomic DNA of two
      patients from this region revealed that one was homozygous for a G to A
      substitution at the 5' donor splice site of intron 2. This mutation completely
      abolishes normal mRNA splicing. The other patient was a compared of the intron 2
      G-->A substitution and a second allele due to a 4-bp deletion in exon 7. The beta
      subunit mRNA of this allele is unstable, presumably as a result of an early stop
      codon introduced by the deletion. Two novel PCR-based assays were developed to
      detect these mutations. We suggest that one of these assays could be modified and
      used as a rapid screening procedure for 5' donor splice site defects in other
      genes. These results provide a further example of the genetic heterogeneity that
      can exist even in a small geographically isolated population.

PMID- 1390949
TI  - Electrophysiological follow-up of acute and chronic experimental allergic
      encephalomyelitis in the Lewis rat.
AB  - Cortical somatosensory evoked potentials (c-SEP) and flash visual evoked
      potentials (f-VEP) were serially recorded in acute monophasic and chronic
      relapsing experimental allergic encephalomyelitis (EAE) in the Lewis rat. In
      acute EAE, a significantly delayed latency and broadened peak of the c-SEP were
      observed corresponding to the clinical onset, and then returned to normal with
      the disappearance of clinical signs. In chronic EAE, the c-SEP showed the same
      changes as in acute EAE, also reflecting the first attack, remission and
      relapsing phase. However, chronic EAE, when paralysis had recovered in the
      relapsing phase, showed c-SEP abnormalities suggestive of subclinical active
      lesions. In contrast, the f-VEP showed no obvious abnormalities in acute or
      chronic EAE. These findings suggest that the c-SEP is an objective and sensitive
      index for detecting clinical and pathological changes in acute and chronic EAE in
      the Lewis rat.

PMID- 1390951
TI  - Recurrent brief depression and its relationship to seasonal affective disorder.
AB  - Recurrent brief depression (RBD) and seasonal affective disorder (SAD) have been
      both recently described as subgroups of major depression (DSM-III-R). We have
      established a relationship between these two syndromes in a cohort of 42
      outpatients who presented themselves to a clinic for seasonal affective disorder
      at the Psychiatric Department of the University of Bonn, FRG. Our preliminary
      data indicate that 31% of the patients who were diagnosed as suffering from
      either SAD or its subsyndromal form (S-SAD) can also be categorized as RBD (RBD
      seasonal) in a 1-year observation period. During the time span of 1 year RBD
      seasonal patients had a mean number of 20 (SD 9) episodes compared with 6 (SD 5)
      episodes (P less than 0.001) in the group of seasonal patients without BRD. These
      episodes were accentuated in fall/winter and outnumbered those in spring/summer
      significantly (P less than 0.001). The mean duration of each episode was 4.6 (SD
      2.6) days in the RBD-seasonal group and 21.8 (SD 29) in the non-RBD-seasonal
      group. Patients with RBD-seasonal experienced seasonal changes as more of a
      problem and reported a lower percentage of first-degree relatives with a history
      of depression than the non-RBD-seasonal group.

PMID- 1390950
TI  - Prospective long-term follow-up of depressed patients with and without suicide
      attempts.
AB  - This 4-6-year prospective follow-up study compared reactive depressives with (n =
      48) and without suicide attempts before index admission (n = 24). Both groups
      showed a favourable course and outcome concerning psychiatric diagnoses (DSM
      III), psychopathology, social integration, and social functioning as well as
      displaying a nearly identical course and outcome. In both groups, two patients
      committed suicide attempts during the follow-up period. 2 (1) male patients from
      the group with suicide attempts committed suicide.

PMID- 1390952
TI  - Schizoaffective disorders with and without onset in the puerperium.
AB  - The premorbid and sociodemographic features, long-term course and long-term
      outcome (on average 23.8 resp. 26.8 years after onset of illness) were compared
      in 30 female schizoaffective patients with onset of their illness during the
      puerperium and 60 female schizoaffective patients with onset at other times. The
      majority of premorbid and sociodemographic variables as well as course parameters
      were similar in the two groups. Most of the few differences (in age at first
      manifestation, marital state at onset, presence of stable heterosexual
      relationship before onset, acuteness of onset, presence of life events) are
      closely connected with the inclusion and exclusion criteria applied for the
      puerperal disorders (exclusion of patients with preexisting illness or
      psychiatric symptoms during pregnancy, inclusion only if onset was within 6 weeks
      of parturition). The puerperal schizoaffective disorders began more frequently
      with a schizomanic episode and less frequently with a schizodepressive episode
      than did the non-puerperal schizoaffective disorders, a finding which perhaps
      reflected the "pathoplastic" role of the puerperium on psychotic disorders.
      Several significant differences were found regarding the long-term outcome
      (frequency of persistent alterations, level of global functioning and disability,
      non-achievement of the expected social development, loss of autarky), confirming
      earlier findings that puerperal disorders generally have a better outcome than
      other psychotic disorders.

PMID- 1390953
TI  - Is the DSM-III-R category of mood disorders too broad? Personality findings.
AB  - In the DSM-III and DSM-III-R the affective or mood category has been widened and
      mood-incongruent psychotic affective illness (MICPAI) included. The present study
      was undertaken to determine whether this broad mood category is still
      homogeneous. Personality factors were used as parameters. Minnesota Multiphasic
      Personality Inventory findings of 54 patients with MICPAI were compared with
      those of 21 probands with a DSM-III typical affective disorder and with those of
      15 DSM-III schizophrenics. It was shown that MICPAI differed significantly from
      typical affective disorder, but not from schizophrenia, in particular regarding
      the subscales "schizophrenia" and "psychopathic deviate". When MICPAI was
      subdivided into the depressed and manic type, the depressed type was found to be
      more closely related to schizophrenia (with respect to the subscales "paranoia"
      and "schizophrenia"), whereas the manic type hardly differed from affective
      disorder. Whether this result is due to diagnostic inaccuracies is discussed. Our
      finding that MICPAI differs from typical affective disorder with respect to
      personality is in accordance with heredity and outcome studies demonstrating that
      MICPAI is associated with a higher risk for schizophrenia in first-degree
      relatives and with worse outcomes when compared with typical affective disorder.
      It can thus be concluded that the decision to include MICPAI in the affective or
      mood category of the DSM-III or DSM-III-R has rendered this category more
      heterogeneous.

PMID- 1390954
TI  - Functional motor asymmetries correlated with clinical findings in unmedicated
      schizophrenic patients.
AB  - Motor asymmetries were investigated in 28 unmedicated schizophrenic in-patients
      and 32 healthy controls. Of the patients, who were assessed as right-handers by a
      handedness questionnaire, 46.4% changed their motor laterality in at least one
      part of the tapping test series, probably because of a decrease of functional
      hemispheric asymmetry. These patients were characterized by more pronounced
      psychotic symptoms than those who did not change motor laterality. According to
      the tapping frequency, two groups of patients could be distinguished: the high-
      and the low-frequency group. In both groups certain tapping data could be
      correlated with characteristic clinical features. While the findings in the high
      frequency group point to an enhanced activation level of the right hemisphere and
      appear to be correlated with the onset of positive symptoms and better prognosis,
      the findings in the low-frequency group may be a reflection of a disturbed
      function of the left frontal region and seem to be correlated with a gradual
      chronic development of predominant negative symptoms with worse prognostic
      implications.

PMID- 1390956
TI  - Nocturnal plasma levels of cytokines in healthy men.
AB  - Nocturnal cytokine levels were measured serially in 12 healthy male volunteers
      for 12 h, including 8 h of polygraphically monitored nocturnal sleep. Plasma
      concentrations of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) were determined in 30-min intervals by enzyme
      linked immunoadsorbent assays. In some subjects cytokines were not detectable at
      all. In the remaining volunteers (27% for IL-1 beta, 58% for IL-6 and TNF-alpha,
      respectively) occasional values near to the detection limits (DL) of the assays
      could be measured. With respect to IL-1 beta and IL-6, plasma levels above the DL
      were significantly more frequent during sleep than during the preceding time of
      wakefulness. No temporal association with NREM or REM episodes could be shown.
      TNF-alpha values above the DL were randomly distributed across the 12-h period
      investigated. It is concluded that in a considerable percentage of healthy
      subjects small amounts of cytokines are released at night. Release of IL-1 beta
      and IL-6 is temporally associated with sleep, whereas the release of TNF-alpha is
      not. It remains to be established whether nocturnal cytokine release reflects
      either an interaction between sleep and host defense mechanisms or a sleep
      independent circadian rhythmicity.

PMID- 1390955
TI  - Facial expression and emotional face recognition in schizophrenia and depression.
AB  - Twenty-three acute schizophrenics, 21 acute major depressives (Research
      Diagnostic Criteria), and 15 normal controls participated in a study on facial
      expression and emotional face recognition. Under clinical conditions, spontaneous
      facial expression was assessed according to the affective flattening section of
      the Scale for the Assessment of Negative Symptoms. Under experimental laboratory
      conditions involuntary (emotion-eliciting interview) and voluntary facial
      expression (imitation and simulation of six basic emotions) were recorded on
      videotape, from which a raterbased analysis of intensity or correctness of facial
      activity was obtained. Emotional face recognition was also assessed under
      experimental conditions using the same stimulus material. All subjects were
      assessed twice (within 4 weeks), controlling for change of the psychopathological
      status in the patient groups. In schizophrenics, neuroleptic drug influence was
      controlled by random allocation to treatment with either haloperidol or perazine.
      The main findings were that schizophrenics and depressives are characterized by
      different quantitative, qualitative, and temporal patterns of affect-related
      dysfunctions. In particular, schizophrenics demonstrated a trait-like deficit in
      affect recognition and in their spontaneous and voluntary facial activity,
      irrespective of medication, drug type and dosage, or extrapyramidal side-effects.
      In depressives a stable deficit could be demonstrated only in their involuntary
      expression under emotion-eliciting interview conditions, whereas in the postacute
      phase a reduction in their voluntary expression became apparent. Differences in
      patterns of affect-related behavioral deficits may reflect dysfunctions in
      different underlying psychobiological systems.

PMID- 1390957
TI  - A comment and a reply to the paper by Kristinn Tomasson et al.: "Failed and short
      seizures associated with prior electroconvulsive therapy".

PMID- 1390959
TI  - Body weight and water intake of guinea pigs: influence of single caging and an
      unfamiliar new room.
AB  - No changes in body weight are observed if adult male guinea pigs are removed from
      their groups and kept singly in their home enclosure. In contrast, subjects
      markedly lose weight and show a marked reduction of water intake if isolated from
      their groups and caged singly in an unfamiliar test room. It is recommended that
      if guinea pigs have to be caged singly, they should remain in their home room,
      for enabling them to express their need for oldfactory/auditory contact with
      conspecifics.

PMID- 1390958
TI  - Transnational stability of gender differences in schizophrenia? An analysis based
      on the WHO study on determinants of outcome of severe mental disorders.
AB  - Gender-specific analyses of the multinational WHO-Determinants of Outcome-Study
      (including 1,292 cases from 10 countries) demonstrate the transnational stability
      of major findings on gender differences in schizophrenia: Male patients have an
      earlier mean age at onset in all countries. In female patients, the distribution
      of the age at onset shows a second peak after age 40 years. No gender differences
      on nuclear symptoms of schizophrenia can be detected, but on uncharacteristic
      symptoms, particularly some aspects of the illness behaviour, differences appear.
      This investigation supports the transcultural validity of gender differences
      found in the German ABC-Schizophrenia-Study and in the Danish-German Psychiatric
      Case Register studies.

PMID- 1390960
TI  - Microvascular transposition of the arterial supply to the testis of the boar.
AB  - The origin of the arterial supply to a testis was changed in 7 boars with a
      microsurgical technique. A. testicularis was connected, end to side, to a branch
      of the femoral artery. The capillary blood flow was unchanged, indicating viable
      transplants. The temperature difference between testis and body disappeared after
      the surgery, indicating an interruption of the heat transfer in the pampiniform
      plexus. The lower values of the histological score and the possibly lower
      peripheral plasma concentration of testosterone after the arterial by-pass may
      indicate a physiological importance of the counter current exchange.

PMID- 1390961
TI  - Cardiac arrhythmias during experimental induction and management of myocardial
      infarction in the dog.
AB  - The experimental production of a myocardial infarction (MI) in the dog was
      achieved adopting a new catheter technique. After induction of the MI, a variety
      of arrhythmias appeared and were classified according to the Lown-classification
      as more or less severe. The therapy was achieved with antiarrhythmics class 1-111
      (Vaughn-Williams classification) for late premature ventricular beats or
      couplets. Sinus tachycardia was often terminated by occular or sinus carotis
      pressure or a new selective sinus blocking agent. Results showed Amiodarone to be
      the drug of choice in the treatment of severe arrhythmias (Lown IV and V) like
      triplets or salves of extrasystolies. Ventricular fibrillation always resulted in
      the death of the animal, because fibrillation was not convertible by direct
      current cardioversion, endovenous injection of Lidocaine or even internal cardiac
      massage. The registration of hemodynamic parameters (left ventricular end
      diastolic pressure, wedge pressure, pulmonary and aortic pressure) was shown to
      be important in controlling the therapy, as well as blood gas and electrolyte
      analysis.

PMID- 1390962
TI  - Evaluation of a psychological treatment package for treating pain in juvenile
      rheumatoid arthritis.
AB  - We examined the utility of psychological treatment procedures for children with
      high levels of pain associated with juvenile rheumatoid arthritis (JRA). By the
      use of a multiple baseline across subjects design, four children were assigned to
      an immediate treatment group, and four children to a delayed treatment group. The
      six-session treatment included relaxation training, electromyogram, and thermal
      biofeedback for the child; mothers were trained in the use of behavioral
      techniques for managing physical therapy and school attendance. Visual inspection
      of the data indicates small changes on children's self-reported pain diary scores
      for mean pain and ratings of high (greater than 5 on a 10-point visual analogue
      scale) pain periods, with 50% to 62% showing at least a 25% reduction in pain
      immediately after treatment, and 62% to 88% showing a 25% reduction by 6-month
      follow-up. Maternal reports of changes paralleled those of the children.
      Comparisons of Mann-Whitney U-tests conducted pre- and posttreatment indicated no
      differences for children's ratings of mean pain or +5 pain ratings between the
      immediate and delayed treatment groups; greater improvement for the immediate
      treatment group was noted on maternal reports of both mean pain (p < 0.05) and +5
      pain (p < 0.5) ratings. The reduction of pain reports from pretreatment to follow
      up was significant for children's mean pain (p = 0.02), +5 pain ratings (p =
      0.02), and mother's reports of mean pain (p = 0.03) and +5 pain periods (p =
      0.01). Maternal reports of the number of pain-related behaviors that the child
      exhibited also declined (p < 0.05). No reduction in physical therapist's ratings
      of pain during evaluation were noted. No increases in maternal reports of child's
      psychological adjustment problems were reported following treatment. Results
      provide modest support for the use of psychological interventions with patients
      with JRA.

PMID- 1390963
TI  - Changing patterns of hospital use for patients with musculoskeletal disease in
      Michigan, 1980 to 1987.
AB  - Over the past 10 years there have been dramatic changes in health care financing
      in the United States, such as Medicare's Prospective Payment System for
      hospitalized Medicare beneficiaries, and in health services delivery, such as the
      growth in health maintenance organizations and other forms of managed care. These
      changes have occurred largely in response to payors' concerns about the rising
      cost of health care. A study of such changes in financing and delivery, and how
      specific groups of patients are affected is necessary so that the effects of
      these changes on patients' health can be determined. We examined the
      hospitalization rates for patients with musculoskeletal diseases in Michigan from
      1980 through 1987. During this period, the overall age-adjusted hospitalization
      rates decreased 7.0% per year (p = 0.001). The decrease occurred less for
      surgical discharges (6.0% per year) than for medical discharges (8.6% per year)
      (p < 0.001). While these overall trends are of interest, they obscure disease
      specific trends that vary significantly from both the overall, and the medical
      and surgical trends. For example, while surgical discharges, in general declined,
      procedures related to major joint and limb reattachment (DRG #209) increased at a
      rate of 6.3% per year. And while medical discharges in general decreased over
      this period, discharges for osteomyelitis increased 5.4% per year. The patterns
      of disease-specific trends offers insight into the possible causes for these
      changes. Finally, it is important to understand the epidemiology of hospital use
      to evaluate the effects of new medical care delivery and payment systems on the
      care of subsets of patients.

PMID- 1390964
TI  - 1991 in review. Research, leadership, AF relationship.

PMID- 1390965
TI  - Health care in the United States. A thousand points of blight.

PMID- 1390966
TI  - Multiple testing in a rheumatoid arthritis trial: statistical comparison of two
      therapies with respect to several endpoints.

PMID- 1390967
TI  - Statistical analyses for research in arthritis when assessing change.

PMID- 1390968
TI  - Validation of the NIH activity record: a quantitative measure of life activities.
AB  - This article reports the results of the validation of a life activity record. We
      devised a self-administered daily log (the NIH Activity Record, ACTRE), for
      persons with rheumatoid arthritis (RA), which recorded specific daily activities
      over a 24-hour period and identified the level of physical effort for each task.
      In addition, each activity was assigned a level of pain, fatigue, difficulty,
      competence, meaningfulness and enjoyment. Twenty-one persons with RA completed
      the log. They underwent an articular examination (AI) (Ritchie Articular Index)
      as well as completed the following self-reports: Psychosocial Adjustment to
      Illness Scale (PAIS); The Feeling Tone Checklist (FTC), a measure of fatigue; The
      Modified Health Assessment Questionnaire (ALI); and the Pain and Disability Index
      (PDI). Significant correlations were found between fatigue measured by ACTRE and
      FTC (p = 0.028); pain measured by ACTRE, PDI (p = 0.002), and (p = 0.01) and the
      visual analog scale in the ALI (p = 0.0002). Pain experienced while performing
      self-care measured by ACTRE correlated with AI (p = 0.001) and ALI (p = 0.0013).
      Difficulty with self-care activities on the ACTRE correlated with difficulty (p =
      0.007) and pain (p = 0.012) on the ALI. The ACTRE is a valid measure of symptoms
      and perceptions that can be quantified, and is unique in that it identifies
      specific daily activities likely to produce them.

PMID- 1390969
TI  - Effect of active hand exercise and wax bath treatment in rheumatoid arthritis
      patients.
AB  - The effect of active hand exercise and warm wax treatment was evaluated in 52
      rheumatoid arthritis patients randomized into four groups: (1) both exercise and
      wax bath, (2) exercise only, (3) wax bath only, and (4) controls. Treatment was
      given three times a week for 4 weeks. Deficits in flexion and extension in digits
      II-V bilaterally, grip function, grip strength, pain, and stiffness were measured
      before and after the treatment period. The control group was measured at
      corresponding times. Wax bath treatment followed by active hand exercise resulted
      in significant improvements of range of motion (ROM) and grip function. Active
      hand exercise alone reduced stiffness and pain with nonresisted motion and
      increased ROM. Wax bath alone had no significant effect.

PMID- 1390970
TI  - Physical fitness levels in children with polyarticular juvenile rheumatoid
      arthritis.
AB  - Children with juvenile rheumatoid arthritis (JRA) often exhibit fatigue and
      prolonged exercise recovery. Improved fitness through physical conditioning has
      not been a goal of standard medical or physical treatment regimens for JRA, and
      fitness levels of children with JRA have rarely been studied. We compared
      physical fitness in 20 6 to 11-year-old patients with polyarticular JRA with sex
      , age-, and size-matched controls, using the Health Related Physical Fitness Test
      (HRPFT), a national, standardized, norm-referenced test. We correlated fitness
      scores with summary joint counts, and with an articular severity index (sum of
      joint swelling, tenderness, pain, and limited range for each child). The results
      showed that children with polyarticular JRA were less physically fit than
      normally active (noncompetitively athletic) children of the same sex, age, and
      size. There was no statistically significant relationship between increased joint
      counts, and/or disease severity scores, and reduced fitness scores. This suggests
      that physical fitness levels are less related to degree of "disease activity"
      than is often thought. We conclude that (1) a readily available, nationally
      standardized fitness test can be used to assess children with JRA: and (2)
      fitness levels and measures of disease activity do not correlate. We believe that
      multiple factors, perhaps including family, physician, and school concerns about
      potential disease exacerbation following exercise, may account for the low
      fitness levels observed in children with JRA.

PMID- 1390971
TI  - Americans with Disabilities Act provokes a lot of questions.

PMID- 1390972
TI  - 'Most MSV presidents develop weight problems'.

PMID- 1390973
TI  - 'Reasonable, collegial' effort expected from new drug board.

PMID- 1390974
TI  - Dr. Terrell's pesthouse.

PMID- 1390976
TI  - Merkel cell tumor in an HIV-positive patient.

PMID- 1390975
TI  - New percutaneous shunt procedure for bleeding varices: case report.

PMID- 1390977
TI  - Resection arthroplasty of the acromial clavicular joint.

PMID- 1390978
TI  - ADA: a new language.

PMID- 1390979
TI  - Purifying antibody-plasminogen activator conjugates.

PMID- 1390980
TI  - Protein radiolabeling with Bolton-Hunter reagent in surfactant reversed micelles
      in organic solvent.

PMID- 1390981
TI  - Synthesis of poly(ethylene oxide) with heterobifunctional reactive groups at its
      terminals by an anionic initiator.

PMID- 1390982
TI  - Uptake by macrophages of a biotinylated oligo-alpha-deoxythymidylate by using
      mannosylated streptavidin.
AB  - Streptavidin substituted with mannose residues increased by 20-fold the
      intracellular concentration of a biotinylated dodecakis(alpha-deoxythymidylate)
      in macrophages by comparison with the uptake of free oligodeoxynucleotide.
      Streptavidin, the bacterial homologue of the very basic avidin, which does not
      contain any carbohydrate moieties and is a neutral protein, was substituted with
      12 mannose residues in order to be recognized and internalized by mannose
      specific lectins on the surface of macrophages. A 3'-biotinylated and 5'
      fluoresceinylated dodecakis (alpha-deoxythymidylate) was synthesized and bound
      onto mannosylated streptavidin. The conjugate was isolated, and by using flow
      cytometry, it was shown that the uptake of fluoresceinylated
      oligodeoxynucleotides bound to mannosylated streptavidin by macrophages is 20
      fold higher than that of free oligodeoxynucleotides and that the uptake was
      competively inhibited by mannosylated serum albumin. Glycosylated streptavidin
      conjugates recognizing specific membrane lectins on different cells provide the
      possibility to target biotinylated antisense oligodeoxynucleotides and to
      increase the biological effect of these chemotherapeutic agents.

PMID- 1390983
TI  - Covalent linkage of ruthenium polypyridyl compounds to poly(L-lysine), albumins,
      and immunoglobulin G.
AB  - A series of ruthenium polypyridyl complexes has been covalently bound to poly(L
      lysine), bovine serum albumin, human serum albumin, ovalbumin, and immunoglobulin
      G using different binding methods. The conjugation ratios and the luminescence
      properties of the bioconjugates are reported. All conjugates show nonsingle
      exponential decay curves. Quenching of the emission by oxygen has been studied.

PMID- 1390984
TI  - Preparation of micelle-forming polymer-drug conjugates.
AB  - Adriamycin, a hydrophobic anticancer drug, was conjugated with poly(ethylene
      oxide)-poly(aspartic acid) block copolymers composed of various lengths of each
      block copolymer segment ranging from 1000 to 12,000 in molecular weight and from
      10 to 80 units, respectively. Conjugation was achieved without precipitation by
      adjusting the ratio of adriamycin to aspartic acid residues of the block
      copolymer and the quantity of DMF used for the reaction. Thus obtained conjugates
      showed high water solubility irrespective of a large amount of the conjugated
      adriamycin. Furthermore, these conjugates were found to form micellar structures
      with a hydrophobic inner core and a hydrophilic outer shell. This micellar
      architecture may be utilized for effective drug targeting.

PMID- 1390985
TI  - Cytotoxicity of chimeric (human-murine) monoclonal antibody BR96 IgG, F(ab')2,
      and Fab' conjugated to Pseudomonas exotoxin.
AB  - We have made antigen-specific cytotoxic reagents by conjugating the chimeric
      antibody BR96 (chiBR96) to Pseudomonas exotoxin A (PE), as either native PE or a
      truncated form (LysPE40) devoid of the cell-recognition region (domain I). PE
      kills cells by ADP-ribosylation of elongation factor 2, thereby inhibiting
      protein synthesis. Chimeric BR96 immunotoxins were constructed by chemical
      conjugation of the toxin to Fab', F(ab')2, and intact IgG and purified by anion
      exchange and gel-filtration chromatography. Chimeric BR96 [IgG and F(ab')2]
      immunotoxins were cytotoxic against tumor cell lines displaying the BR96 antigen,
      with EC50 values ranging from 0.1 to 110 pM. Immunotoxins constructed with
      chiBR96 Fab' were 50-100-fold less cytotoxic. Competition analysis showed that
      the immunotoxins were specifically active through their BR96 antigen-binding
      ability. The binding of chiBR96-PE and chiBR96-LysPE40 to antigen was equivalent
      to that of BR96 itself and these immunotoxins were found to internalize very
      rapidly, displaying 90% of their cytotoxicity within 1 h. Binding assays
      determined that chiBR96 F(ab')2-LysPE40 bound as well as chiBR96-LysPE40;
      however, chiBR96 Fab'-LysPE40 bound 20-fold less efficiently. The chiBR96 Fab'
      LysPE40 internalized similarly to the F(ab')2 or the IgG immunotoxins. Therefore,
      the chiBR96 Fab'-LysPE40 immunotoxin is less cytotoxic toward target cells
      because of reduced antigen binding. This is may be due to the monovalent nature
      of chiBR96 Fab'-LysPE40. This study shows that the monoclonal antibody chiBR96
      Pseudomonas exotoxin A immunotoxins can be effective at inhibiting protein
      synthesis in target cells.

PMID- 1390986
TI  - Light-induced coupling of aqueous-soluble proteins to liposomes formed from
      carbene-generating phospholipids.
AB  - A novel bilayer-forming phospholipid analogue with a photoactivatable carbene
      generating head group was synthesized and characterized with respect to molecular
      structure and light-induced reactivity. N'-(1,2-Dimyristoyl-sn-glycero-3
      phosphoethyl)-N-[m-[3- (trifluoromethyl)diazirin-3-yl]phenyl]thiourea (PED) was
      prepared by thiocarbamoylation of synthetic dimyristoylphosphatidylethanolamine
      with 3-(trifluoromethyl)-3-(m-isothiocyanophenyl)diazirine. PED formed liposomes
      in aqueous media. Gel to liquid-crystalline transitions occurred at 10.5 degrees
      C. Neither PED- nor PED/dimyristoylphosphatidylcholine mixed liposomes underwent
      major structural changes when photoactivated. Liposome sizes, determined by
      electron microscopy, were not altered upon light exposure. PED combines the
      advantages of facile synthesis and timed carbene reactivity by photoactivation at
      wavelengths greater than or equal to 320 nm. Conditions used for PED
      photoactivation did not inactivate catalytically active or complex-forming
      proteins. Light-induced binding of aqueous-soluble proteins to PED containing
      liposomes was attained through photoactivation in the presence of myoglobin,
      streptavidin, or trypsin. The proteins mentioned were utilized to characterize
      carbene-initiated ligand coupling. Procedures described establish a new and
      versatile method for the formation of proteoliposomes.

PMID- 1390987
TI  - Use of N-terminal modified poly(L-lysine)-antibody conjugate as a carrier for
      targeted gene delivery in mouse lung endothelial cells.
AB  - A DNA targeted delivery and expression system has been designed based on an N
      terminal modified poly(L-lysine) (NPLL)-antibody conjugate, which readily forms a
      complex with plasmid DNA. Monoclonal antibodies against the cell-surface
      thrombomodulin conjugated with NPLL were used for targeted delivery of foreign
      plasmid DNA to an antigen-expressing mouse lung endothelial cell line in vitro
      and to mouse lungs in vivo. In both cases significant amounts of DNA can be
      specifically bound to the target cells or tissues. Specific gene expression was
      observed in the treated mouse lung endothelial cells.

PMID- 1390988
TI  - Photoaffinity labeling of scallop myosin with 2-[(4-azido-2
      nitrophenyl)amino]ethyl diphosphate: identification of an active site arginine
      analogous to tryptophan-130 in skeletal muscle myosin.
AB  - The ADP photoaffinity analogue 2-[(4-azido-2-nitrophenyl)amino]ethyl diphosphate
      (NANDP) was used to photolabel the ATP binding site of scallop myosin.
      Approximately 1 mol of NANDP per mol of myosin was trapped at the active site by
      complexation with vanadate and manganese. ADP, but not AMP, inhibited trapping of
      NANDP. The trapped NANDP photolabeled up to 37% of the myosin upon UV
      irradiation. Papain subfragment-1 prepared from the photolabeled myosin was
      digested with trypsin, and the major photolabeled tryptic peptides were isolated
      by reversed-phase HPLC. The amino acid sequence of the major labeled peptide was
      X-Leu-Pro-Ile-Tyr-Thr-Asp-Ser-Val-Ile-Ala-Lys, where X represents the
      photolabeled amino acid Arg128. Previously, Trp130 of rabbit skeletal muscle
      myosin has been shown to be photolabeled by NANDP [Okamoto, Y., and Yount, R. G.
      (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 1575-1580]. Scallop and rabbit skeletal
      muscle myosin display a high degree of sequence similarity in this region with
      Arg128 in an equivalent position as Trp130. These results suggest that the
      composition of the purine binding site is analogous in both myosins and that Arg
      and Trp play a similar role in binding ATP, despite the marked differences of
      their side chains.

PMID- 1390989
TI  - Synthesis of novel 1,4,7-triazacyclononane-N,N',N"-triacetic acid derivatives
      suitable for protein labeling.

PMID- 1390990
TI  - Spectrophotometric method for the determination of a bifunctional DTPA ligand in
      DTPA-monoclonal antibody conjugates.
AB  - A simple spectrophotometric method was developed to quantitate micromolar
      concentrations of a bifunctional DTPA ligand in DTPA monoclonal antibody (mAb)
      conjugates. Titration of a brightly colored 1:2 yttrium (III) complex of arsenazo
      III with the ligand 1B4M-DTPA obeyed Beer's law over the concentration range 0
      2.0 microM 1B4M-DTPA at 652 nm. From a calibration plot of absorbance versus 1B4M
      molarity, concentrations of 1B4M-DTPA conjugated to mAb were determined. Mole
      ratios of 1B4M-DTPA to mAb agreed satisfactorily with the ratios obtained by a
      radioanalytical technique using carbon-14-labeled 1B4M-DTPA and a binding assay
      using 111In. The spectrophotometric method was applied successfully to the
      preparation of 1B4M-DTPA mAb anti-TAC, a mAb conjugate used in clinical trials of
      90Y radioimmunotherapy.

PMID- 1390991
TI  - An improved method for labeling monoclonal antibodies with samarium-153: use of
      the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6-
      methyldiethylenetriaminepentaacetic acid.
AB  - Samarium-153 (153Sm) radioimmunoconjugates of the monoclonal antibody K-1-21 were
      produced using the bifunctional chelate 2-(p-isothiocyanatobenzyl)-6-
      methyldiethylenetriaminepentaacetic acid (Mx-DTPA). The specific activity (up to
      150 MBq mg-1) and percent retained immunoreactivity (greater than 75%) were
      similar to that of 153Sm-K-1-21 conjugates formed with cyclic DTPA anhydride
      (cDTPAa). In vivo biodistribution studies showed specific localization of 153Sm
      Mx-DTPA-K-1-21 to target antigen implants and higher blood pool and lower uptake
      in liver, spleen, kidney, and bone when compared to 153Sm-cDTPAa-K-1-21. The
      improved in vivo distribution of 153Sm-Mx-DTPA-K-1-21 should result in lower
      radiotoxicity to nontarget tissues when used for radioimmunotherapy purposes.

PMID- 1390992
TI  - [Tuberculosis update. A critical view of the new diagnostic techniques].

PMID- 1390993
TI  - [Inhibition of total and active E-rosettes mediated by serum from tubercular
      patients].
AB  - AIM: To study the effect of tuberculous patients' serum upon normal lymphocytes
      in order to determine possible inhibition factors of immune response. PATIENTS
      AND METHODS: We studied total E-rosette formation (4 degrees C, RET) and active
      rosette formation (37 degrees C, REA) in tuberculous patients in different
      stages: mild (n:36), moderate (n:28), severe (n:24) and a control group of 32
      patients. The same determinations were studied in normal circulating lymphocytes
      (LN) incubated before with serum from tuberculous patients (SP), serum of normal
      individuals (SN) and in Tc-199 medium. RESULTS: The number of RET and REA in
      tuberculous patients of different stages were significantly lower to the ones of
      the control group (p less than 0.01, p less than 0.05). This differences were
      also found when we compare the number of RET and REA after the incubation of LN
      with SP and SN respectively (p less than 0.01, p less than 0.05). SUMMARY:
      Tuberculous patients showed an impaired ability to form RET and REA. The
      incubation of normal lymphocytes with serum from tuberculous patients reduced
      significantly its capacity to form rosettes.

PMID- 1390994
TI  - [Tuberculosis in 7 general hospitals in Andalusia. Grupo Andaluz para el Estudio
      de las Enfermedades Infecciosas].
AB  - BACKGROUND: To know the clinical features of tuberculosis in our environment, to
      evaluate its diagnostic techniques and therapeutic options as well as the
      evolution of patients. PATIENTS AND METHODS: Multicenter retrospective study of
      1115 patients with tuberculosis, diagnosed between 1984 and 1988 in the
      population based areas of 7 Hospitals from Andalusia (Spain). RESULTS: The mean
      age was less than 40 ages, the exponential growing of the number of cases a year
      in which the influence of drug addicts could be an important factor, an elevated
      proportion (45%) of extrapulmonary tuberculosis and disseminated forms, and a
      social environment of 20% of cases being alcoholics or drug addicts. A good use
      of diagnostic techniques is recorded, although the use of culture as diagnostic
      tools is lacking. The usual treatment was three drugs for nine months. The global
      evolution seems good. However a global mortality of 6.4% is recorded, mainly in
      disseminated forms and among patients with risk factors for developing
      tuberculosis. SUMMARY: We have seen an increment among tuberculosis cases, as
      well as a change in the clinical spectrum of the disease, linked to social
      illness and drug addiction. The diagnostic approach to tuberculosis seems to be
      appropriate. The follow up of patients is somewhat confusing.

PMID- 1390995
TI  - [Serodiagnosis in pulmonary tuberculosis. Clinical evaluation].
AB  - The IgA, IgG, IgM and IgG subsets antibodies levels were determined in 200
      patients with pulmonary tuberculosis and compared to three control groups: 80
      healthy individuals (50 with negative PPD skin test, 30 with positive PPD skin
      test), 30 leprosy patients and 20 patients with different pulmonary diseases. The
      technique used was an enzyme linked assay. As antigens, purified tuberculin and
      Ag60 from M. bovis were used. There were not statistically significant
      differences between antibody levels among all control groups studied, but when we
      compare the level in control groups with that observed in tuberculous patients,
      they showed higher levels of IgA, IgG, IgM, IgG2 (p less than 0.01) and IgG4 (p
      less than 0.05). A definite diagnosis of tuberculosis of the lung should only be
      established if the patient showed to be positive to IgG plus IgA or IgM and in
      special cases to IgG1, reaching then a diagnostic efficacy of 90% in a patient
      population with a 68% of positive smears for acid-fast bacilli.

PMID- 1390997
TI  - [DNA amplification using PCR in the diagnosis of tuberculosis].
AB  - BACKGROUND: To evaluate the DNA amplification technique of M. tuberculosis with
      PCR in clinical samples. METHODS: We have studied 57 clinical samples of 49
      patients using PCR and culture in conventional media. We evaluate the final
      diagnosis of tuberculosis depending upon the bacteriologic results of all
      available samples. RESULTS: We reached a 58% sensitivity and 100% specificity. In
      9 samples with positive PCR the culture was negative. The samples belonged to 9
      patients with tuberculosis (4 with active disease and 5 with past microbiological
      diagnosis). In 32 samples with negative PCR test, the microorganism was isolated
      in 9 cases. SUMMARY: More studies are needed before PCR technique could be
      recommended for widespread use in the diagnosis of tuberculosis. Its long
      duration, the equipment needed and the false negative results are among its
      limitations.

PMID- 1390996
TI  - [Antigenic response against PPD and antigen 60 in tubercular patients: single
      antigen versus the combined test].
AB  - We analyze serum samples from 70 patients with pulmonary tuberculosis and 50
      healthy individuals. The antigenic activity (IgG) against protein purified
      antigen (PPD) and antigen 60 (A60) from M. tuberculosis. Thirteen patients were
      also HIV infected, and three patients had AIDS defined by the presence of
      disseminated tuberculosis. The test using antigen alone showed a 77% sensitivity
      and 74% specificity when PPD is used. When A60 was used, both values improved
      (81% sensitivity, 94% specificity). The use of a combined test (PPD and A60)
      improves the sensitivity (89%) but reduces the specificity (82%). The HIV
      infected patients showed similar responses to those of other patients. The
      combined use of different antigens might be useful for diagnosing tuberculosis.

PMID- 1390998
TI  - [Isolation of Yersinia enterocolitica 0:8 in Spain].
AB  - BACKGROUND: We presented three cases of enterocolitis due to Yersinia
      enterocolitica 0:8. METHODS: We use common isolation media, pathogenicity markers
      and plasmid analysis. RESULTS: The study of genetic and biochemical
      characteristics of the strains showed that they belonged to 1B biotype, 0:8
      serotype, and that they not carry the virulence plasmid. However, they have
      pathogenicity markers that were considered typical of highly virulent strains.
      SUMMARY: This are the first isolations of this particular serotype in Spain and
      they showed, as it happens in other European countries, the spread of serotype
      0:8 around the world.

PMID- 1390999
TI  - [Osteoarticular infections in children].
AB  - We presented a retrospective review of osteoarticular infections diagnosed at
      Sant Joan de Deu Hospital from Barcelona, in the last 10 years (1981-1990). A
      total of 127 arthritis and 113 osteomyelitis were recorded in children aged from
      a few days to 15 years. This represents a 3.5% of all infectious diseases
      patients during the study period. The most common microorganism was S. aureus
      (52.3%) followed by Brucella (8.2%) and Salmonella as well as Streptococcus
      agalactiae (7.3% each). The most common involved joint were hip and knee in
      arthritis cases, but long bones (tibia and humerus) in osteomyelitis cases.

PMID- 1391000
TI  - [Comparison of the new Granada medium and the ICON-strep B test in the detection
      of group B streptococci in pregnant patients].
AB  - The detection of group B streptococci by the ICON Strep-B test an enzyme
      immunoassay, and culture in new Granada Medium was compared in tubes and plates
      in a total of 200 vaginal specimens from pregnant women. The group B streptococci
      were cultured in new Granada medium from 33 of these specimens (incidence of
      16.5%). Compared with culture in new Granada medium, the sensitivity and
      specificity of the ICON-Strep B test were 66.6 and 100%, respectively. Because of
      their poor sensitivity, we do not recommend the use of these rapid test as the
      only basis for GBS detection.

PMID- 1391001
TI  - [Automated method for yeast identification: ATB 32 C].
AB  - The aim of this study was to evaluate the ATB 32 C (API system) automatic medium
      for identifying yeasts in clinical samples. A total of 101 yeasts strains were
      studied, representing 8 genera and 18 different species, identified by
      conventional means. All 32 microdomes of the track, including dehydrated
      substrates, were inoculated in a semi-solid media (C medium). After their
      incubation at 30 degrees C for 48 hours, the reading device ATB 1520 and the
      computer of ATB system the reading and automatic interpretation of the results.
      Using the ATB method, 85 strains were identified (84%) at species level, 9 at
      genus level and a non-conclusive or unacceptable profile was recorded in 7
      strains. From all clinically important yeasts species, a total of 96% were
      identified by ATB method according to conventional methods. From all non
      clinically relevant species, ATB 32 C identified correctly 23 strains (78%). ATB
      32 C method is a good alternative approach to conventional techniques for
      identifying yeasts in clinical samples.

PMID- 1391002
TI  - [Vaccines against Neisseria meningitidis].

PMID- 1391004
TI  - [Diarrhea in a woman from Peru].

PMID- 1391003
TI  - [Etiopathogenic aspects of Lyme disease].

PMID- 1391005
TI  - [Diarrhea in an HIV-positive patient].

PMID- 1391006
TI  - [In vitro activity of 11 antimicrobial agents against clinical isolates of
      Acinetobacter spp].

PMID- 1391007
TI  - [Incidence of germs of the Neisseriaceae family in the pharyngeal flora of
      healthy adults].

PMID- 1391008
TI  - [Urinary tract infection caused by Haemophilus influenzae and Haemophilus
      parainfluenzae].

PMID- 1391009
TI  - [Invasive aspergillosis in acquired immunodeficiency syndrome].

PMID- 1391010
TI  - [Infectious endocarditis caused by Staphylococcus intermedius in a patient
      infected with HIV].

PMID- 1391011
TI  - [Acute arthritis associated with Q fever].

PMID- 1391012
TI  - [Molecular bases for the serotypes of group B streptococci].

PMID- 1391013
TI  - [AIDS: descriptive study and survival analysis of the 1st 40 cases].
AB  - AIM: To analyze the epidemiologic and clinical features, the survival as well as
      length of stay of the first 40 AIDS cases seen at the internal Medicine
      Department of the Virgen de la Arrixaca Hospital (Murcia, Spain). METHODS:
      Prospective study from September 1988 through July 1991. AIDS criteria used were
      the CDC (1987) ones. The survival analysis was performed using the Kaplan-Meier
      method. RESULTS: Thirty-four patients were male (85%) and six female (15%), with
      a mean age of 39 years. Eighteen (45%) were homo or bisexual, 11 drug addicts
      (27.5%), 8 (20%) had sexual contacts with prostitutes and/or drug addicts. Two
      patients were recipients of blood products and in one case no risk could be
      determined. Opportunistic infections were the first AIDS criteria in 75% of
      cases. Among the most frequent are P. carinii pneumonia (17.5%), CNS
      toxoplasmosis (15%) and cryptosporidiosis (12.5%). In 20% of cases a Kaposi's
      sarcoma developed. The probability of survival after three months was 91% +/-
      9.6, at 7 months 79.5% +/- 15.0 and at 15 months 72.5 +/- 18. Overall, 90% of
      patients had at least one hospital admission, and 27.7% were hospitalized for 50%
      of more of their survival time. CONCLUSIONS: We recorded an increased number of
      AIDS cases since 1988, being most of them homo-bisexual male patients, with
      opportunistic infections as first manifestation. We noticed also high proportion
      of cases of heterosexual transmission.

PMID- 1391015
TI  - [Penicillin-resistant pneumococci and the empirical use of penicillins in the
      treatment of community-acquired acute pneumonia].
AB  - The prevalence of penicillin-resistant pneumococci in our environment has raised
      questions about the effectiveness of penicillin as empiric treatment for
      community-acquired pneumonia cases. We followed prospectively all patients with
      community-acquired pneumonia from February 1989 through January 1990. We also
      reviewed retrospectively the treatment and evolution of all patients with
      confirmed pneumococcal pneumonia diagnosed between January 1988 and January 1990.
      A total of 115 patients with probable pneumococcal pneumonia were prospectively
      followed-up. Seventy-nine were treated with penicillin (benzyl- and
      aminopenicillin), and the remaining patients with macrolides, cephalosporin drugs
      or both. Five patients died (4%). There is no significant differences between
      mortality in penicillin-treated patients (2 cases) when compared to patients with
      other treatments (3 cases). Twenty-three patients have confirmed pneumococcal
      pneumonia. Among them, 8 (24%) had penicillin-resistant pneumococci (5 strains
      with MIC: 0.12-1 microgram/ml; 3 strains with MIC: 2 micrograms/ml). No
      differences were recorded regarding demographic data, predisposing conditions,
      underlying diseases, severity of pneumonia or the outcome of treatment between
      penicillin and non-penicillin treatment groups. Also, no differences were seen in
      clinical response and mortality when patients with pneumonia due to penicillin
      resistant pneumococci treated with penicillin were compared to the ones treated
      with other drugs. In two patients, initially treated with erythromycin,
      progression of the pneumonia was recorded. Erythromycin resistant pneumococci
      (MIC greater than 8 micrograms/ml) were recovered from transthoracic needle
      biopsy. Both patients recovered well when beta-lactam antibiotics were
      prescribed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391014
TI  - [Molecular epidemiology of Salmonella enterica poisoning: correlation of the
      serotype and protein profile and plasmid DNA analysis].
AB  - Food-borne diseases nosocomial outbreaks due to Salmonella enterica strains have
      a high incidence nowadays. We describe here an outbreak that occurred in July
      1990 in the Malaga University Hospital, that only involves one shift of health
      care workers. Salmonella enterica was detected in stool samples from HCW and a
      first analysis revealed the presence of two different antibiotic susceptibility
      patterns (resistotypes) among isolated strains. Two months after the outbreak
      started, the CNVIS (Majadahonda, Spain) confirmed the presence of two different
      serotypes (bovismorbificans and enteritidis). The delayed availability of the
      results (due to the lack of specific sera needed in most of the clinical
      Laboratories) was responsible for finishing only a partial and restricted
      epidemiologic study in terms of source identification for one particular serotype
      as well as for the antimicrobial resistance studies. The molecular identification
      techniques, particularly the electrophoretic protein profile could overcome these
      problems.

PMID- 1391017
TI  - [Use of PCR in the epidemiological identification of Campylobacter spp].
AB  - BACKGROUND: With arbitrary primer PCR technique it is possible to obtain
      amplification lane patterns easily and with good reproducibility from the genomic
      DNA of bacteria studied. There is also no need for prior information regarding
      the DNA sequence. METHOD: This method implies two cycles of amplification with
      low stringency, followed by a PCR of high stringency. RESULTS: Using the above
      mentioned technique, we were able to show that Campylobacter spp from clinical
      samples could be separated as well as different strains from the same species.
      CONCLUSIONS: According to our results as well as the ones from different authors
      applied to other microorganisms, we can assume that the method could be used in
      any bacterial species for epidemiologic studies purposes.

PMID- 1391016
TI  - [Epidemiological factors and vaginal flora changes in vaginal bacteriosis
      (bacterial vaginosis)].
AB  - BACKGROUND: The aim of this study was to know the modifications of the vaginal
      bacterial flora that occurs in bacterial vaginosis and to know the involvement of
      these microorganisms and the influence of several epidemiologic factors in the
      etiology of this disease. METHODS: We studied, by using semiquantitative cultures
      and GLC, vaginal washings from 50 healthy women and 50 women with bacterial
      vaginosis. RESULTS: The most remarkable results were the high sensitivity of
      Amsel's criteria and their good correlation with GLC. Women with bacterial
      vaginosis showed a great increase of CFUs/ml of Gardnerella vaginalis, Mycoplasma
      hominis, Ureaplasma urealyticum and several species of anaerobic bacteria, and an
      important decrease of the amounts of aerobic lactobacilli. The main epidemiologic
      factor among those that were studied was the use of IUDs. CONCLUSIONS: The
      appearance of bacterial vaginosis is associated with the increase of the amounts
      of G. vaginalis, Bacteroides or related genera (Prevotella, Porphyromonas), and
      probably M. hominis and U. urealyticum, also being associated to a decrease of
      the amounts of aerobic lactobacilli. These facts are probably related with
      alteration in the ecologic relationship lactobacilli/G. vaginalis/anaerobic
      bacteria.

PMID- 1391018
TI  - [Gastroenteritis caused by verotoxin-producing Escherichia coli O157.
      Presentation of 2 cases].
AB  - Verotoxin-producing Escherichia coli strains have been associated with acute
      hemorrhagic colitis since 1982. We have systematically investigated this pathogen
      in our laboratory, in all stool samples submitted for culture during a fourteen
      month period, by using MacConkey sorbitol agar to isolate non sorbitol fermenting
      Escherichia coli strains. Coated latex particles with an antiserum against
      Escherichia coli O157 were used to detect O157 serogroup Escherichia coli. A
      completed serological study and verotoxin assay was performed in all positive
      strains. We have found two non-related cases of verotoxigenic Escherichia coli
      infection in two children. In one case, the main clinical picture was an acute
      hemorrhagic colitis and the other one was a diarrhea without presence of blood,
      with fever and vomiting. Both cases improved without antimicrobial treatment. No
      systemic complications appeared in any of the cases during the infection. The
      infection incidence was 0.07% of all positive stool cultures. The few documented
      cases of this infection in our country should encourage to investigate this
      pathogen in order to know its real incidence in our environment.

PMID- 1391019
TI  - [Resistance of Haemophilus influenzae and Haemophilus parainfluenzae to beta
      lactam antibiotics. Characterization of the beta-lactamases].
AB  - We have studied the susceptibility to ampicillin and the characteristics of the
      beta-lactamase activity of the 169 Haemophilus spp. strains (128 H. influenzae,
      40 H. parainfluenzae and one H. paraphrophilus) isolated during 12 months, years
      1988-1989, in the Hospital del Mar clinical microbiology laboratory. Our
      objective was to know in the strains of our center the frequency of those
      resistant or slightly susceptible to ampicillin, the role of beta-lactamases in
      the loss of susceptibility and the type of enzymes involved. Susceptibility was
      studied by diffusion for all the antibiotics tested and also confirmed by
      dilution for ampicillin and other beta-lactam antibiotics. Beta-lactamase
      production was identified by nitrocefin hydrolysis. The isoelectric point of the
      beta-lactamase and the identification of their types were determined by analytic
      isoelectric focusing. The presence of the codifying gene of the TEM-1 enzyme was
      studied by hybridization with a TEM-1 probe. Of the H. influenzae strains 35 were
      ampicillin resistant, one moderately susceptible and of the H. parainfluenzae
      strains six were resistant and two moderately susceptible; all were susceptible
      to the combination of amoxicillin/clavulanic acid. The ampicillin-resistant
      strains were beta-lactamase producers. In 40 strains, by isoelectric focusing,
      the type TEM-1 was identified and the hybridization was positive; in one H.
      parainfluenzae strain a beta-lactamase of pl 5.8 was observed and the
      hybridization with TEM-1 probe was negative. The three strains moderately
      susceptible to ampicillin did not produce beta-lactamase.

PMID- 1391020
TI  - [Helicobacter pylori].

PMID- 1391021
TI  - [Current status of studies on sensitivity to antifungal agents].

PMID- 1391023
TI  - [Inflammatory edema of the eyelid and orbital pain].

PMID- 1391022
TI  - [Inflammation of the back of the hand in an intravenous drug addict].

PMID- 1391024
TI  - [Murine typhus. Efficacy of treatment with ciprofloxacin].

PMID- 1391025
TI  - [Isolation of Cryptococcus neoformans in the pleural fluid of a cirrhotic
      patient].

PMID- 1391027
TI  - [Sternoclavicular pneumococcal arthritis and multiple myeloma].

PMID- 1391026
TI  - [Bacteremic pneumonia caused by Moraxella catarrhalis in a non-immunosuppressed
      patient].

PMID- 1391028
TI  - [Hematogenous spondylitis caused by Bacteroides fragilis].

PMID- 1391029
TI  - [Significant bacteremias not detected by the BACTEC NR 730 system].

PMID- 1391030
TI  - [Myalgias and bacteremia].

PMID- 1391031
TI  - The NIH human gene therapy symposium.

PMID- 1391032
TI  - Retrovirus-mediated gene transfer as an approach to analyze neuroblastoma relapse
      after autologous bone marrow transplantation.
AB  - Disseminated neuroblastoma is a malignancy of children often treated by intensive
      chemotherapy/radiotherapy followed by autologous bone marrow transplantation
      (ABMT). A high proportion of those treated subsequently relapse. It is unknown if
      relapse is a consequence of residual disease in the patient or of contaminating
      malignant cells remaining in the infused marrow, which, of necessity, is
      harvested and stored prior to ablative chemotherapy/radiotherapy. The assumption
      that residual cells in the infused marrow contribute to relapse has lead to the
      adoption of marrow purging prior to reinfusion. However, neither the necessity
      nor the efficacy of the procedure have been established. We now show how
      retroviral-mediated gene transfer using the LNL6 vector may resolve this issue.
      Clonogenic neuroblastoma cells in patient marrow can be transduced and the NEOR
      gene detected by observing individual neuroblastoma cell colony growth in G418,
      and by polymerase chain reaction (PCR) of individual colonies. Efficiency of
      transduction is between 0 and 13.5%. If marrow is exposed to LNL6 prior to
      infusion and marked cells are detected at the time of relapse, this would
      demonstrate that infused marrow contributed to disease recurrence. The technique
      could then be used to analyze the efficacy of marrow purging techniques. Since
      normal progenitor cells from these patients are also marked, the technique can be
      used to study factors that modify reconstitution and transducibility of infused
      marrow. Clinical studies using this approach have now begun.

PMID- 1391033
TI  - Use of cell-free retroviral vector preparations for transduction of cells from
      the marrow of chronic phase and blast crisis chronic myelogenous leukemia
      patients and from normal individuals.
AB  - Marrow cells were exposed to the LNL6 or G1N safety-modified variants of the N2
      retrovirus, which contain the G418 bacterial resistance gene neo. The frequency
      of acquisition of the G418 resistance phenotype following exposure to LNL6 or G1N
      was compared among hematopoietic progenitor cells from the marrow of patients
      with chronic phase chronic myelogenous leukemia (CML), blast crisis CML, or from
      nonleukemic individuals. Under the conditions of our experiments, the myeloid
      committed progenitor cells from 3 of 6 nonleukemic individuals, 9 of 18 chronic
      phase CML patients, and 2 of 4 blast crisis CML patients acquired resistance to
      at least 1 mg/ml G418 following incubation with cell-free supernatants from the
      PA317 LNL6 or PA317 G1N producer cell lines. Ten of the 32 colonies growing up in
      0.8 mg/ml G418 from chronic-phase marrow exposed to LNL6 were shown to contain
      the neo gene by polymerase chain reaction (PCR) assay of DNA. These results were
      consistent with estimates of the transduction frequency based on acquisition of
      resistance to G418 as the number of colonies growing under G418 selection was
      always greater at 0.8 mg/ml G418 than at higher concentrations of G418 (1.0-1.4
      mg/ml). The average transduction frequency at each G418 concentration (1.0, 1.2,
      and 1.4 mg/ml) in cells from blast crisis CML cells ranged from 2 to 14%, as
      measured by acquisition of G418 resistance. Chronic-phase CML showed slightly
      lower average frequencies of transduction (0.6-2.8% of the colonies are G418
      resistant). The average transduction frequency of cells from nonleukemic marrow
      was as high as that seen from the marrow of chronic-phase CML
      individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391034
TI  - High-efficiency gene transfer mediated by adenovirus coupled to DNA-polylysine
      complexes.
AB  - Employment of recombinant viruses as gene transfer vectors is limited by
      constraints on the size and functional design of the genetic material to be
      transferred as well as potential safety hazards deriving from obligatory co
      transfer of viral genetic elements. As an alternative strategy that capitalizes
      on the efficient cellular entry mechanisms of viruses, we have derived adenovirus
      polylysine-DNA complexes whereby foreign DNA is transferred bound to the exterior
      of the virion. This linkage was accomplished utilizing an antibody bridge in
      which a monoclonal antibody was rendered competent to carry DNA by the attachment
      of a polylysine residue. Attachment of the antibody-polylysine to the virus was
      by virtue of the antibody's specificity for the virion. The resulting vector
      system mediates high-efficiency gene transfer to target cells in vitro. In
      addition, this vector design allows greatly enhanced flexibility in terms of the
      size and design of heterologous sequences that can be transferred. Since this
      strategy selectively exploits viral entry functions, which are independent of
      viral gene expression, the potential exists to derive vectors that avoid the
      hazards deriving from transfer of parent virus genome.

PMID- 1391035
TI  - Expression of chimeric neo-Rev response element sequences interferes with Rev
      dependent HIV-1 Gag expression.
AB  - Recombinant plasmids containing reiterated human immunodeficiency virus type 1
      (HIV-1) Rev response element (RRE) sequences were constructed to suppress Rev
      dependent HIV-1 Gag expression. The mammalian expression vectors pMAMneo
      containing one, three, or six repeats of the RRE sequence were cotransfected with
      a HIV-1 HTLV-IIIB proviral DNA into HeLa cells. All three RRE expression plasmids
      reduced replication of HIV-1 with similar efficacy. Furthermore, the chimeric
      expression vector pCMV neoRRE6 x ----(containing six copies of the RRE sequence)
      was used to establish HeLa cell lines constitutively expressing RRE. A plasmid
      encoding a Rev-dependent HIV-1 p24 Gag protein was cotransfected with the wild
      type Rev expression plasmid into three different RRE-expressing HeLa cell lines.
      p24 Gag protein production in the culture supernatants of the HeLaneoRRE cells
      was compared with two neo-expressing cell lines. Although all cell lines
      (HeLaneoRRE, HeLaneo) displayed similar transfection efficiencies, p24 Gag
      protein synthesis was markedly reduced in the RRE-expressing cell lines in
      comparison to the control cells.

PMID- 1391036
TI  - First International Workshop on Human Gene Transfer.

PMID- 1391037
TI  - The treatment of patients with melanoma using interleukin-2, interleukin-4 and
      tumor infiltrating lymphocytes.

PMID- 1391038
TI  - Ex vivo gene therapy of familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by a
      deficiency in the receptor that clears low density lipoprotein (LDL) from the
      serum (reviewed in Ref. 1 and 2). Patients with one abnormal LDL receptor allele
      have moderate elevations in plasma LDL and suffer premature coronary artery
      disease (CAD). Approximately 5% of all patients under 45 who have had a
      myocardial infarction carry this trait. Patients with two abnormal LDL receptor
      genes (homozygous deficient patients) have severe hypercholesterolemia and life
      threatening coronary artery disease in childhood. Strategies for treating
      patients with FH are directed at lowering the plasma level of LDL. In
      heterozygotes, this is accomplished through the administration of drugs that
      stimulate the expression of LDL receptor from the normal allele (2). This
      therapeutic approach is not effective in the treatment of homozygous deficient
      patients, especially those that retain less than 2% of residual LDL receptor
      activity. Partial amelioration of hyperlipidemia has been achieved in some
      homozygous deficient patients by diverting the portal circulation through a
      portacaval anastomosis (3) and by chronic plasmapheresis therapy (4). A more
      direct approach has been to correct the deficiency of hepatic LDL receptor by
      transplanting a liver that expresses normal levels of LDL receptor. Three
      patients that survived this procedure normalized their serum LDL-cholesterol (5
      9). We have used an authentic animal model for FH, the Watanabe Heritable
      Hyperlipidemic rabbit (WHHL), to develop gene therapies for the homozygous form
      of FH (10-13). The WHHL rabbit has a mutation in its LDL receptor gene which
      renders the receptor completely dysfunctional (12) leading to severe
      hypercholesterolemia, diffuse atherosclerosis, and premature death. The potential
      efficacy of gene therapy for FH is supported by a series of studies we have
      performed in the WHHL rabbit in which we have achieved metabolic improvement (14
      18). Liver tissue was removed from WHHL rabbits and used to isolate hepatocytes
      and establish primary cultures. A functional rabbit LDL receptor gene was
      transduced into a high proportion of hepatocytes using recombinant retroviruses,
      and the genetically corrected cells were transplanted into the animal from which
      they were derived. Transplantation of the genetically corrected, autologous
      hepatocytes was associated with a 30-40% decrease in serum cholesterol that
      persisted for the duration of the experiment (4 months, Ref. 18). Recombinant
      derived LDL receptor RNA was detected in liver for at least 6 months. There was
      no apparent immunological response to the recombinant derived LDL
      receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1391039
TI  - Spo0A activates and represses its own synthesis by binding at its dual promoters.
AB  - The Spo0A protein of Bacillus subtilis controls the onset of sporulation by
      regulating transcription of various genes in both positive and negative manners
      depending on the promoters affected. The expression of the spo0A gene occurs from
      two promoters (Pv,Ps), separated by 148 bp, and transcription switches from Pv to
      Ps early in the sporulation program. DNase I footprint analysis of the spo0A
      promoter region revealed three distinct sites of Spo0A binding: -4 to +19
      relative to Pv, -17 to +1 relative to Ps, and a region between Pv and Ps. The Pv
      region and the region between the two promoters was sufficient for repression of
      Pv. Induction of Ps also required these regions which are upstream of -52
      relative to Ps. Mutant Spo0A proteins containing asp----asn mutations at asp10
      and asp56 were inactive in repression of the abrB promoter in vivo yet still
      retained DNA-binding activity. The results presented are consistent with a model
      in which the phosphorylated form of Spo0A acts directly at its promoters to
      achieve induction of Ps and repression of Pv. These effects at the spo0A promoter
      were independent of the presence of the major kinase, KinA.

PMID- 1391040
TI  - Bacterial sporulation.

PMID- 1391041
TI  - The interaction between Bacillus subtilis sigma-A (sigma A) factor and RNA
      polymerase with promoters.
AB  - The P2 promoter from Bacillus subtilis sigma-A (sigma A) operon and the strong
      phi 29 phage G3b promoter were used to study their interactions with free sigma A
      and with RNA polymerase holoenzymes (E sigma A and E sigma 70). No binding of
      free sigma A to the tested promoters was observed, suggesting that the B subtilis
      free sigma A does not bind promoter by itself for the initiation of RNA
      transcription. Different footprints of B subtilis RNA polymerase holoenzyme (E
      sigma A) on the P2 and G3b promoters were detected. The footprint on the P2
      promoter is mainly in the -10 downstream region of the bottom strand (noncoding
      strand) DNA and limited on the top strand (coding strand), whereas the footprints
      on both strands of the G3b promoter are very clear. These results suggest that
      the footprint regions of RNA polymerase on a promoter and the strength of its
      binding to the promoter depend on the properties of the specific promoter DNA
      sequence. It also suggests that the -10 and its downstream regions are more
      important than the -35 region for the formation of the E sigma A-P2 promoter open
      complex. Footprints of B subtilis E sigma A and E coli E sigma 70 on the same G3b
      promoter are very similar on the top strand but different on the bottom strand,
      with the footprint being about 17 bases wider (-4 to +13) in the case of E coli E
      sigma 70. Since this region contains most of the bases involved in promoter DNA
      melting, we suggest that E coli and B subtilis RNA polymerases have different
      efficiency in forming the open complex with heterologous promoter DNA during
      initiation of transcription.

PMID- 1391042
TI  - The effect of supercoiling on the in vitro transcription of the spoIIA operon
      from Bacillus subtilis.
AB  - The spoIIA operon codes for an alternative sigma factor which appears in the
      early stages of a sigma factor expression cascade during sporulation in Bacillus
      subtilis. We have used a single round in vitro transcription assay to probe
      requirements for transcription initiation at the spoIIA promoter. Core RNA
      polymerase or holoenzyme containing sigma A was reconstituted with sigma H
      protein and used to transcribe the spoIIA promoter. Formation of heparin
      resistant transcription initiation complexes required that the spoIIA template be
      supercoiled. Topoisomers of the spoIIA template were created and transcribed at
      various temperatures. Changes in the superhelicity of template DNA had a
      significant influence on the amount of transcription complexes formed at the
      spoIIA promoter.

PMID- 1391043
TI  - Intergenic suppression of stage II sporulation defects by a mutation in the major
      vegetative sigma factor gene (rpoD) of Bacillus subtilis.
AB  - The Bacillus subtilis intergenic suppressor mutations crsA and rvtA, previously
      shown to restore sporulation competence to a variety of strains containing stage
      0 sporulation defects, also suppress lesions in the stage II sporulation genes
      spoIIF, spoIIN and spoIIJ. They do not rescue sporulation in other stage II
      through stage V sporulation mutations. Cells containing spoIIN, spoIIF96 and
      spoIIJ::Tn917 mutations fail to transcribe spoIID, a late stage II gene.
      Introduction of crsA47 into spoIINts279, spoIIF96, or spoIIJ::Tn917 mutant
      backgrounds circumvents the need for the spoIIF, IIN, and IIJ products, restoring
      both expression of spoIID, and sporulation competence.

PMID- 1391044
TI  - Effect of mutant small, acid-soluble spore proteins containing cysteine or
      tryptophan on DNA properties in vivo and in vitro.
AB  - Two derivatives of the alpha/beta-type small acid-soluble spore protein (SASP)
      SspCwt have been constructed, each containing a residue potentially useful for
      physico-chemical analysis of protein-protein or protein-DNA interactions. In one
      mutant protein (SspCtrp) residue 27 (Met) was replaced by Trp; in the second
      (SspCcys) residue 48 (Asn) was replaced by Cys. Both mutant proteins were
      expressed in Bacillus subtilis spores at levels similar to those of SspCwt, and
      SspCcys and SspCtrp restored ultraviolet light (UV) resistance and plasmid
      negative supercoiling in spores lacking major alpha/beta-type SASP to levels
      similar to those restored by SspCwt. While the purified mutant proteins bound
      more weakly to DNA than SspCwt, all three had the same relative affinity for
      different DNAs, ie poly(dG).poly(dC) greater than poly(dG-dC).poly(dG-dC) greater
      than pUC19, and purified SspCcys and SspCtrp gave the same pattern of DNase
      protected bands with pUC19 as SspCwt. Binding of SspCcys or SspCtrp to
      poly(dG).poly(dC) in vitro also prevented the formation of cyclobutane type
      cytosine dimers upon UV irradiation, as does binding of SspCwt. These data
      indicate that the two mutant proteins are extremely similar to SspCwt in their
      interaction with DNA, and thus may be useful in probing SASP-SASP and SASP-DNA
      interactions directly by physical or chemical techniques. Indeed, binding of
      SspCtrp to poly(dG).poly(dC) resulted in a 2.5-fold enhancement of the proteins
      Trp fluorescence.

PMID- 1391045
TI  - Protein filaments may initiate the assembly of the Bacillus subtilis spore coat.
AB  - The Bacillus subtilis spore coat consists of three morphological layers: a
      diffuse undercoat, a striated inner coat and a densely staining outer coat. These
      layers are comprised of at least 15 polypeptides and the absence of one in
      particular, CotE, had extensive pleiotropic effects. Only a partial inner coat
      was present on the spores which were lysozyme-sensitive. The initial rate of
      germination of these spores was the same as for the wild type but the overall
      optical density decrease was greater apparently due to the loss of the incomplete
      spore coat from germinated spores. Suppressors of the lysozyme-sensitive
      phenotype had some outer coat proteins restored as well as some novel minor
      polypeptides. These spores still lacked an undercoat and germinated as did those
      produced by the cotE deletion strain. The CotE protein was synthesized starting
      at stage II-III of sporulation, long before the appearance of the coat on spores
      at stage IV-V. Despite its apparent hydrophilic properties, this protein was
      present in the crude insoluble fraction from sporulating cells. CotE was not
      solubilized by high or low ionic strength buffers not by detergents used for the
      solubilization of membrane proteins. Either 8 M urea or 6 M guanidine HC1 was
      required and dialysis against a low ionic strength buffer resulted in aggregation
      into long, sticky filaments. Both the CotE and CotT spore coat proteins appeared
      to be necessary for the formation of these filaments. Each of these proteins
      contains sequences related to a bovine intermediate filament protein so their
      interaction could result in an analogous structure.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391046
TI  - Early spo gene expression in Bacillus subtilis: the role of interrelated signal
      transduction systems.
AB  - The early spo genes are subject to a number of different control mechanisms. We
      found that at least one histidine kinase, SpoIIJ, is important for the expression
      of early spo genes but that two others, ComP and DegS, also affect sporulation,
      especially when SpoIIJ is absent. This indicates the existence of a signal
      transduction network which may gather information from several sources to feed
      into the sporulation pathway. Early spo gene expression is inhibited by
      overproduction of two response regulators, SpoOF and ComA. This effect is
      eliminated by the elevated presence of their cognate histidine kinases, SpoIIJ
      and ComP, respectively. This suggests that the unphosphorylated response
      regulators cause the inhibition of sporulation.

PMID- 1391047
TI  - Suppressors of a spo0A missense mutation and their effects on sporulation in
      Bacillus subtilis.
AB  - The spo0A gene product of Bacillus subtilis is a transcriptional regulator that
      is required for the initiation of sporulation. It has not been possible to
      isolate mutations that suppress the sporulation defect caused by spo0A null
      mutations. We describe the isolation and characterization of mutations that
      suppress the severe sporulation defect caused by a spo0A missense mutation
      (spo0A9V). Two suppressor mutations, spa2 and spa4, have been characterized in
      combination with, and separated from, the spo0A9V mutation. Both were located in
      the carboxyl half of Spo0A, in the putative DNA binding, transcriptional
      activation region. spa2 was in codon 174, causing a leucine to arginine change
      (spo0A174LR), and spa4 was in codon 162 (of 267), causing a histidine to arginine
      change (spo0A162HR). spa2 and spa4 significantly restored sporulation to the
      spo0A9V mutant, however, the appearance of heat resistant spores was delayed
      relative to wild-type. When separated from spo0A9V, that is, as single mutations
      in spo0A, spa4 caused a delay in sporulation, while spa2 allowed apparently
      normal sporulation. The spa mutations caused interesting phenotypes when combined
      with other early sporulation mutations. spa2 suppressed the sporulation defect
      caused by spo0E11. This was most easily seen in spo0E11 abrB double mutants,
      which had a much more severe sporulation defect than the spo0E11 single mutant.
      That is, spo0E11 and abrB mutations caused a synthetic (synergistic) sporulation
      phenotype. Both the spa2 spo0A9V and the spa4 spo0A9V alleles greatly enhanced
      the sporulation defect caused by mutations in spoIIJ, spo0J and spo0K. The
      significance of these synthetic sporulation defects is discussed.

PMID- 1391048
TI  - The spoIIN279(ts) mutation affects the FtsA protein of Bacillus subtilis.
AB  - The spo-279(ts) mutation, originally thought to be located in the spoIIG operon
      of Bacillus subtilis, has been mapped in close proximity but outside of the
      spoIIG locus. This mutation defines a new gene, spoIIN, located midway between
      the spoIIG and the spoVE loci, and whose product is required for successful
      completion of the asymmetric septation step. The spoIIN locus was cloned using a
      combination of 'walking steps' upstream from the spoIIG region and hybridization
      screening of a bacteriophage lambda library. Sequencing of DNA fragments able to
      rescue the spoIIN279(ts) mutation revealed that the spoIIN locus is identical
      with the B subtilis counterpart of the Escherichia coli ftsA gene. After cloning
      the ftsA region from a strain containing the spoIIN279(ts) mutation we found that
      this mutation converts the ninth residue of the FtsA protein from serine to
      asparagine. The spoIIN279(ts) mutation, which is recessive, leads to
      filamentation during growth at 42 degrees C and causes defective formation of the
      sporulation septum at this non-permissive temperature. The FtsA protein is
      therefore required for proper cell septation, both during vegetative growth and
      sporulation. Possible additional roles of FtsA during sporulation are discussed.

PMID- 1391050
TI  - Use of a new integrational vector to investigate compartment-specific expression
      of the Bacillus subtilis spoIIM gene.
AB  - The product of the spoIIM gene of Bacillus subtilis is required for complete
      septum migration and forespore engulfment during sporulation. To investigate
      whether expression of spoIIM is required in the forespore compartment of the
      sporangium, we have constructed a new integrational vector, pKSV7, which contains
      temperature-sensitive replication functions derived from pE194ts. The presence of
      the conditionally defective replication origin greatly stimulates plasmid
      excision when sporulation occurs at the permissive temperature. This facilitates
      the use of a genetic technique employed by Illing et al to distinguish genes
      whose expression must occur in the forespore from genes that may be expressed
      exclusively in the mother cell compartment. The results of the
      integration/excision experiments using pKSV7 support the conclusion that spoIIM
      must be expressed in the forespore. Biochemical analysis of forespore and mother
      cell fractions suggests that spoIIM is also expressed in the mother cell. The
      conditional integrational vector pKSV7 replicates at high copy number in E coli
      and allows the identification of inserts in the polylinker cluster by disruption
      of alpha-complementation and thus should be useful for other kinds of genetic
      manipulations in B subtilis.

PMID- 1391049
TI  - Cloning and sequencing of the Bacillus megaterium spoIIA operon.
AB  - The spoIIA operon of Bacillus megaterium has been cloned and the nucleotide
      sequence determined. The spoIIA sequence contains three open reading frames
      coding for putative proteins of 116 aa, 147 aa, and 253 aa; the first and the
      third genes are preceded by a ribosomal binding site. The genes are in the same
      order as those of B subtilis and B licheniformis. The deduced amino acid
      sequences of these three open reading frames show 78-92% homology with SpoIIAA,
      SpoIIAB and SpoIIAC of B subtilis and B licheniformis. Northern hybridization
      revealed that B megaterium also has two spoIIA transcripts, 1.77 kb and 2.92 kb,
      attaining maximum expression at t1 and t3, respectively. In addition, homology to
      a possible penicillin binding protein gene upstream and the first part of a spoVA
      operon downstream has been identified on the 3.34-kb fragment. The spoIIA and the
      downstream spoVA promoter regions are highly conserved among these three species.
      Sequence analysis of the spoVA promoter revealed a region upstream to the -35
      that is highly conserved across Bacillus species.

PMID- 1391051
TI  - Evidence that recombination between reiterated sequences in the Bacillus subtilis
      chromosome does not occur via unequal crossing over.
AB  - An experimental system was designed to permit the detection of recombination
      events occurring via unequal crossing over between sister bacterial chromosomes
      in Bacillus subtilis. It exploits the fact that during spore development, genetic
      and metabolic cooperation occurs between two different cell types, only one of
      which survives. During the early stages of sporulation, the two chromosomes of
      the developing sporangiole lie in the same cell and recombination between them is
      possible, in principle. Internal duplications flanking a selectable antibiotic
      resistance gene have been introduced into the spoIIIC, spoIVA and spoVJ genes,
      whose correct expression in the mother cell (non-surviving compartment) is
      necessary for completion of spore development. After incubation in a sporulation
      inducing medium in the absence of selective pressure, these strains sporulate at
      a low frequency and up to 30% of the progeny are Spo-. They result from mosaic
      sporangioles, in which only the chromosome segregated into the mother cell
      compartment of the developing sporangiole contains a reconstituted spo gene. In
      mosaic sporangioles generated by unequal crossing over between sister bacterial
      chromosomes, the insertionally inactivated spo gene, segregated into the pre
      spore compartment, would carry an extra copy of the duplication initially
      present. Analysis of the products of 124 independent recombination events giving
      rise to mosaic sporangioles provided no evidence for the occurrence of unequal
      crossing over.

PMID- 1391052
TI  - A method for the determination of bacterial spore DNA content based on isotopic
      labelling, spore germination and diphenylamine assay; ploidy of spores of several
      Bacillus species.
AB  - A reliable method for measuring the spore DNA content, based on radioactive DNA
      labelling, spore germination in absence of DNA replication and diphenylamine
      assay, was developed. The accuracy of the method, within 10-15%, is adequate for
      determining the number of chromosomes per spore, provided that the genome size is
      known. B subtilis spores were shown to be invariably monogenomic, while those of
      larger bacilli Bacillus megaterium, Bacillus cereus and Bacillus thuringiensis,
      often, if not invariably, contain two genomes. Attempts to modify the spore DNA
      content of B subtilis by altering the richness of the sporulation medium, the
      sporulation conditions (liquid or solid medium), or by mutation, were apparently
      unsuccessful. An increase of spore size with medium richness, not accompanied by
      an increase in DNA content, was observed. The implication of the apparently
      species-specific spore ploidy and the influence of the sporulation conditions on
      spore size and shape are discussed.

PMID- 1391053
TI  - A Bacillus subtilis morphogene cluster that includes spoVE is homologous to the
      mra region of Escherichia coli.
AB  - It is known that there is a strong similarity in amino acid sequence between the
      products of the Escherichia coli morphogenes ftsW (mra region at 2 min) and rodA
      (mrd region at 14 min) and the Bacillus subtilis SpoVE protein which is required
      for spore cortex formation. We show here that the predicted amino acid sequences
      coded for by the genes flanking spoVE are homologous to the products of the E
      coli genes murD and murG, which flank ftsW, and are involved in peptidoglycan
      biosynthesis. During vegetative growth and early stationary phase spoVE is
      cotranscribed with murD and murG in the form of very long polycistronic messages
      originating upstream of murD. However, this transcriptional activity is shut-off
      soon (approximately 1 h) after the cells enter stationary phase, and spoVE is
      then transcribed at two times during sporulation from its own promoter(s).
      Insertional in vitro mutagenesis of the region revealed that although murD and
      murG are essential for normal vegetative growth, spoVE is only required for
      sporulation: spoVE null mutants display a sporulation stage V phenotype
      indistinguishable by light microscopy from the phenotype conferred by the spoVE85
      and spoVE153 alleles that originally defined the locus.

PMID- 1391054
TI  - Achievement of complete Bacillus subtilis microcycle sporulation by the addition
      of S-adenosylmethionine and phospholipids.
AB  - In an attempt to find factors that may be responsible for the initiation of
      sporulation, a system in which the germination and outgrowth phases were separate
      was applied to Bacillus subtilis. Outgrowth of the germinated spores to only the
      primary singlet cells was followed in chemically defined medium. Addition of
      specific metabolites induced the primary singlet cells to sporulate via
      microcycle sporulation. Experiments are described that led to complete
      sporulation by the addition of diaminopimelic acid, S-adenosyl-L-methionine and
      phosphatidylethanolamine.

PMID- 1391055
TI  - Molecular characterization of regulatory elements controlling expression of the
      Bacillus subtilis recA+ gene.
AB  - Expression of the Bacillus subtilis recA gene is induced following DNA damage as
      well as during the development of the competent state. DNA damage-induction of
      the recA gene occurs by a RecA-dependent mechanism, whereas competence-induction
      occurs by a RecA-independent mechanism. To examine the molecular mechanisms that
      control the expression of the recA gene, a deletion analysis of the recA promoter
      region was performed. A regulatory region that is required for repression of recA
      expression was identified upstream of the recA promoter. Deletion of this
      regulatory region derepressed expression and abolished damage-induction of the
      recA promoter. Within this region are sequences similar to the consensus sequence
      that has been identified within DNA damage-inducible promoter regions of other B
      subtilis genes. Another regulatory region was identified that is required for the
      RecA-independent, competence-specific induction of the recA gene. Deletion of
      these sequences significantly reduced competence-induction of the recA promoter.

PMID- 1391056
TI  - Haematospermia.
AB  - Haematospermia, blood in the ejaculate, is a symptom which provokes great anxiety
      in patients due to fears of malignant or sexually transmitted disease. However,
      there is no evidence from the published literature to associate it with any
      serious pathology. The large series of cases indicate that investigation is
      unproductive and that patients do not develop serious disease even after
      prolonged follow-up. Patients presenting with haematospermia warrant a full
      physical examination, including rectal examination, but in the absence of
      physical signs they should then be strongly reassured. Further investigation is
      unnecessary. Coexistent urological symptoms should be investigated appropriately.

PMID- 1391057
TI  - Herpes simplex virus infection in pregnancy and its management.
AB  - Neonatal herpes simplex virus (HSV) infection is considered to be rare in the UK,
      affecting less than 3 per 100,000 live births, but the true incidence is probably
      higher due to under-reporting. In contrast, neonatal HSV infection is more common
      in the USA affecting 1 per 7500 live births overall. Infection in neonates is
      frequently serious and may be fatal.

PMID- 1391058
TI  - Pathophysiological concept of Haemophilus ducreyi infection (chancroid)
AB  - Our knowledge concerning the pathogenesis of infection due to Haemophilus ducreyi
      is incomplete. In order to produce disease, H. ducreyi must presumably penetrate
      the skin of the external genitalia, colonize subcutaneous tissues, then produce
      tissue damage which results in ulcer formation. Penetration of the normal skin
      most likely occurs via minor abrasions. Adherence of H. ducreyi to different cell
      lines in vitro has been described, and might be mediated by adhesions such as
      pili or haemagglutinins. In addition, binding to extracellular matrix proteins
      has also been reported. Extracellular tissue-degrading enzymes were absent from
      broth culture supernatants of H. ducreyi. Such supernatants also failed to
      produce cytopathic effects with established or primary cell lines. Both live and
      heat-killed H. ducreyi organisms were able to produce lesions in a rabbit or a
      mouse model, although ulcer formation was dependent on viable H. ducreyi
      organisms in a recently introduced temperature-dependent rabbit model. With an
      excessive supply of iron, a more prolonged localized inflammatory disease effect
      was observed. Results derived from a subcutaneous chamber model demonstrated
      considerable changes in the expression of outer membrane proteins combined with
      antibody modulation during in vivo growth of H. ducreyi. These might be important
      factors for maintenance of infection in the human host particularly as these
      changes also occur in humans. Despite an increased knowledge of the pathogenesis
      of chancroid, important questions such as growth requirements, bubo-formation,
      role of cell-mediated immunity and ulcer formation are still unanswered. The
      application of molecular biological techniques in order to study these problems
      will be helpful.

PMID- 1391059
TI  - Current smoking habits and genital infections in women.
AB  - A study was undertaken to assess the relationship between current cigarette
      smoking and genital infections. Four hundred women attending a sexually
      transmitted disease clinic were the subjects of the study; of these 212 (53%)
      were cigarette smokers. In women under 20 years of age 70% were smokers. Women
      who smoked were more likely to have multiple partners and be in a lower socio
      economic class or unemployed. The presence of genital warts was commoner in
      smokers. No association was shown between smoking and cervical inflammation or
      dysplasia. The findings suggest that cigarette smoking is a behavioural factor
      which should routinely be identified in the demographic details of women
      attending sexually transmitted disease clinics.

PMID- 1391060
TI  - Factors associated with sexually transmitted diseases among prostitutes in
      Singapore.
AB  - From June to December 1990, 806 prostitutes registered with the STD programme in
      Singapore for regular screening for sexually transmitted diseases (STD) were
      investigated for factors associated with STD incidence in the preceding year. The
      majority were foreigners (92.7% Malaysians and 3.1% Thais). Anal sex (0.4%) and
      intravenous drug use (0.9%) were rare. The overall STD incidence rate was 47.7
      per 100. None was human immunodeficiency virus (HIV) positive. The crude and age
      adjusted risk of STD was found to increase significantly with client load. An
      inverse relationship between condom use and STD risk was also observed. Mean
      condom use among clients was reported as 56.1% for spontaneous use and estimated
      as 75.4% following negotiation for condom use by prostitutes. Although the
      prostitutes negotiated for condom use with majority of the clients (85.5%) who
      did not use condoms spontaneously, they were successful with only about half of
      them (54.4%). Health education should be targeted at clients on the protective
      effects of condom use and at the prostitutes on skills in negotiating condom use.

PMID- 1391061
TI  - IgM-antibodies against T. pallidum detected in sera from mothers of stillborn
      babies in Mozambique by the solid-phase haemadsorption assay (SPHA).
AB  - Serum samples taken at the delivery from 27 syphilitic mothers in Mozambique, 16
      with stillborn babies and 11 with healthy babies were tested upon presence of IgM
      antibodies against T. pallidum by the solid-phase haemadsorption assay (SPHA).
      Fourteen out of the 16 serum samples from mothers with stillborn babies but only
      one out of the 11 samples from mothers with healthy babies were found positive by
      the SPHA test. Clinical signs indicative of syphilis are difficult to find in the
      Maputo area as there were more than 40,000 annual births and only five
      obstetricians when the study was carried out. It is believed that the findings
      may indicate those mothers who were serologically positive with the SPHA test had
      clinically active syphilis and that syphilis might be the cause or a contributory
      cause of death in 14 of the stillborn babies. The SPHA test was easy to perform
      and we recommend its adoption by laboratories with facilities to perform the TPHA
      test.

PMID- 1391062
TI  - Clinical study with recombinant interferon gamma versus interferon alpha-2c in
      patients with condylomata acuminata.
AB  - A multi-centre, randomized, open-label trial was conducted to evaluate the safety
      and efficacy of recombinant interferon (rIFN) alpha-2c versus rIFN gamma in
      patients with recurrent or persistent condylomata acuminata (CA). Thirty-three
      such patients were treated either with 6 micrograms rIFN alpha-2c or with 0.1 mg
      rIFN gamma (both equivalent to 2 x 10E6 IU), single dose, subcutaneously 3 times
      a week for 6 weeks. In case of no complete clearance at week 10, a second course
      of treatment with the other type of rIFN was given. There was no significant
      difference in the complete clearance proportions at week 10 between the two
      treatment groups (3/16 vs 6/17). No relapses occurred in these patients during
      the 16 weeks' follow-up. Further clearances during the follow-up resulted in a
      total complete clearance proportion of 14/33 at the end of study. The treatment
      was well tolerated. Repeated interferon therapy has its place in treating
      persistent or recurrent condylomas.

PMID- 1391063
TI  - Chlamydia trachomatis antigen detection by Chlamydiazyme combined with Chlamydia
      Blocking Reagent verification.
AB  - Several options exist for the detection of chlamydial infection in a routine
      laboratory setting. Enzyme immuno assay (EIA) technology offers rapid turn around
      of results and is less technically demanding than chlamydial cell culture. In
      addition, recently introduced EIA confirmatory reagents have the potential to
      improve the accuracy of EIA detection. We have evaluated one such confirmatory
      reagent (Chlamydia Blocking Reagent, Abbott Laboratories) to determine the
      accuracy of the Chlamydiazyme EIA with special regard to interpretation of low
      absorbance values. An initial series of 192 male urethral specimens showed that
      use of a lowered cut off level (absorbance value 0.05) compared with that
      recommended by the manufacturer increased sensitivity of the EIA from 0.73 to
      0.83, thus motivating studies on this interpretative modification. Of 1101 EIA
      reactive specimens, 65% were determined to be chlamydia positive by the Chlamydia
      Blocking Reagent. The proportion of female cervical specimens that did not
      confirm positive was elevated compared with male urethral specimens, 43% vs. 5.7%
      respectively. In samples yielding absorbance from the recommended cut off level
      to 0.05 (approximately 50% below), the corresponding figures were 78% and 14%
      respectively. In 85 selected EIA reactive samples, examination by a direct
      immunofluorescence staining assay (DFA) (MicroTrak, Syva Inc.) revealed
      elementary bodies in 85% of 67 blocking test positive and in 24% of 18 blocking
      test negative samples. The possibility that Gram-negative bacteria were
      responsible for unconfirmed EIA reactive specimens was investigated using
      bacterial suspensions. While EIA reactivity was noted with several strains for
      Gram-negative bacteria, both the blocking reagent and DFA correctly verified the
      absence of chlamydial antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391064
TI  - Value of bacteriological screening of urine samples from HIV infected patients.
AB  - A retrospective analysis of the results of bacteriological examination of all
      urine samples from adult HIV infected patients admitted to the City Hospital,
      Edinburgh during the year 1 April 1988 to 31 March 1989 was made to assess the
      usefulness of this investigation in HIV positive patients without clinical
      evidence of urinary tract infection.

PMID- 1391065
TI  - Pyogenic abscess caused by Mycobacterium kansasii in advanced AIDS.

PMID- 1391066
TI  - Missed human immunodeficiency virus seroconversion.

PMID- 1391068
TI  - Vulval neurofibromatosis masquerading as genital warts.

PMID- 1391067
TI  - Spinal cord toxoplasmosis in a patient with human immunodeficiency virus
      infection.
AB  - Spinal cord toxoplasmosis occurs rarely in the acquired immunodeficiency syndrome
      (AIDS). It usually presents as a space occupying lesion which makes
      differentiation from a neoplasm difficult. As a result, only 2 of the 5
      previously reported cases have been diagnosed antemortem. We have incorporated
      the clinical details from one further case to describe the clinical features of
      this condition. The clarification of this clinical entity may allow earlier
      diagnosis of this rare condition in the future.

PMID- 1391069
TI  - Regional trends in viral STDs.

PMID- 1391070
TI  - Heterosexual HIV transmission.

PMID- 1391072
TI  - AIDS Literature Index.

PMID- 1391071
TI  - Single dose therapy of anogenital and pharyngeal gonorrhoea with ciprofloxacin.

PMID- 1391073
TI  - [Insulin resistance and arterial hypertension].

PMID- 1391074
TI  - [Clinical heterogeneity of the autistic syndrome: a study of 60 families].
AB  - Sixty families ascertained through a single proband, has helped to better define
      infantile autism as a heterogeneous group of disorders. Forty four patients
      showed a characteristic facio- auricular dysplasia. Twenty four of these, showed
      increased pyruvate and lactate and laboratory findings of metabolic acidosis
      i.e., anion gap above 18 mEq/L or serum bicarbonate below 21 mEq/L but only nine
      of these probands demonstrated reduction of plasma bicarbonate below 18 mEq/lt.
      Plasma amino acids in 17 probands and matched controls showed increased taurine
      with the rest of amino acids significantly (p less than 0.05) below the control
      level. Glutamate and aspartate were also significantly elevated (p less than
      0.05; Student t-test). Segregation analysis in thirty four of these families
      which linked through at least one ancestral family name, suggested autosomal
      recessive inheritance (p = 0.20). Three out of eight probands who received
      megadoses of pyridoxine (Vitamin B6), subjectively gained in language abilities,
      affectivity and response to behavior modification therapy. Five autistic patients
      proved to have clinically defined syndromes: two with the Martin-Bell syndrome,
      and three girls affected respectively with the Rett syndrome, phenylketonuria and
      dicarboxylic aciduria.

PMID- 1391075
TI  - [Serotyping of 48 isolates of Candida albicans: predominance of serotype A over B
      in Venezuela].
AB  - The study of serotyping of isolates of Candida albicans of clinical material
      obtained from different geographic areas of Venezuela suggest that serotype A is
      predominant over type B. These results are in relation with results obtained in
      other countries. Type A serotype is predominant in 57 to 100% in the areas
      studied. Only in 2 cities serotype B was isolated. Both serotypes of Candida
      albicans were observed in intertriginous, mucosal, inguinal and lung forms. These
      studies have allowed us to have information about the predominance of serotypes
      in certain areas of the country.

PMID- 1391076
TI  - [Treatment of patients with panic disorder and an elevated urinary excretion of
      MHPG using imipramine or clonazepam].
AB  - The response to treatment with imipramine or clonazepam was evaluated in patients
      with panic disorder. These patients had a high urinary 3-methoxy-4-hydroxy
      phenylglycol 24 h-excretion and normal plasma lactate levels. Both drugs were
      efficient as anti-panic agents, but clonazepam resulted more efficacious than
      imipramine by the scores of Hamilton Anxiety or Depression Scales. Moreover,
      clonazepam also reduced the anticipatory anxiety.

PMID- 1391077
TI  - [Cytopathogenic effect of diphtheria exotoxin in cultured chick embryo
      fibroblasts].
AB  - One hundred fifty strains of Corynebacterium diphtheriae were studied from
      patients with symptoms of diphtheria and from healthy persons. 136 strains
      (90.67%) belonged to the mitis biotype, 12 (8.0%) and 2 (1.33%) to gravis and
      intermedius biotypes respectively. Toxigenicity was determined by traditional in
      vivo methods with rabbits and plaque immunodiffusion in KL-virulence medium. From
      the 136 mitis biotype strains studied, 130 (95.58%) showed positive toxigenicity
      by both methods and 11 strains (91.66%) from gravis biotype and 2 (100%) of
      intermedius biotype gave same results. The cellular cytotoxicity of the
      diphtheriae toxin was tested on culture of chicken embryo fibroblast and were
      positive in 132 (97.05%) strains of mitis biotype, and in all strains of gravis
      and intermedius biotypes. These results suggest that the cytotoxicity test seems
      to be a more sensitive method for detecting diphtheriae toxin production.

PMID- 1391078
TI  - The solubility of volatile anaesthetics in water at 25.0 degrees C using 19F NMR
      spectroscopy.
AB  - Anaesthetic concentration is very important for the quantitative treatment of
      anaesthesia theory. Traditionally concentration values have been derived from the
      water/gas partition coefficient. However, the values from many investigators show
      discrepancies. This study reports the accurate solubility of methoxyflurane (9.1
      mM), halothane (18.0 mM), enflurane (11.9 mM) and isoflurane (13.5 mM) in water
      at 25.0 degrees C using 19F NMR spectroscopy. The method has advantages in that
      the dissolved molecule in solution can be separately quantified from undissolved
      anaesthetic. Saturated solutions of the anaesthetic agents were prepared in situ
      in a NMR tube to avoid pressure and temperature changes in the solution.

PMID- 1391079
TI  - New fluorescent derivatives of cyclosporin for use in immunoassays.
AB  - The synthesis of new fluorescent derivatives of cyclosporin is described and
      their affinity with the specific Sandoz monoclonal antibody investigated.
      Synthesis was carried out using cyclosporin-C-hemisuccinate as the starting
      material with monodansylcadaverine, 4-bromomethyl-7-methoxycoumarin, and 4
      bromomethyl-6,7-dimethoxycoumarin as labels. After extraction the derivatives
      were purified by HPLC and their binding affinity with the monoclonal antibody
      evaluated by the Incstar Cyclo-Trac SP radioimmunoassay. All three derivatives
      showed good binding and it is suggested that they may be of use in an immunoassay
      for measuring cyclosporin.

PMID- 1391080
TI  - Thermal behaviour and binary phase diagram of (S)-(+)-4,4'-(1-methyl-1,2
      ethandiyl)-bis-(2,6-piperazinedione) (dexrazoxane), a cardioprotective agent, and
      of its (R)-(-)-enantiomer.
AB  - The binary phase diagram of (S)-(+)-4,4'-(1-methyl-1,2-ethandiyl)-bis-(2,6
      piperazinedione), 1 (dexrazoxane), a cardioprotective agent, and of its (R)-(-)
      enantiomer, 2, has been investigated by differential scanning calorimetry (DSC);
      the equimolecular mixture of 1 and 2 corresponds to a racemic compound (racemate)
      whose melting point is higher than that of the enantiomers. Thermal behaviour
      (DSC) is examined and discussed in comparison with the data obtained by other
      physical methods (IR spectroscopy and X-ray powder diffraction).

PMID- 1391081
TI  - Spectrophotometric determination of promethazine by flow injection analysis and
      oxidation by CeIV.
AB  - A flow injection analysis (FIA) procedure is proposed for the determination of
      promethazine. The sample solution is directly injected into the carrier-reagent
      stream which comprises a solution of ceric ions in a sulphuric acid medium. The
      absorbance at 514 nm from the red colour developed by the oxidation of
      promethazine is measured. Effects of foreign substances have been investigated
      and the procedure has been applied to the determination of promethazine in a
      pharmaceutical formulation (tablets).

PMID- 1391082
TI  - Determination of ampicillin in the presence of cloxacillin.
AB  - A spectrophotometric method is described for the assay of ampicillin in the
      presence of cloxacillin in pharmaceutical preparations. It involves the reaction
      of hydrolysed ampicillin with formaldehyde in an acidic phosphate buffer (pH 2.5)
      and measurement of the absorbance of the product at 373 nm after dilution with 2
      M sulphuric acid. The method is selective for ampicillin in the presence of
      cloxacillin. The absorbance had a linear relationship with concentration for the
      range studied (5-35 micrograms ml-1). By this method the ampicillin content of
      combined preparations of ampicillin and cloxacillin has been successfully
      determined in capsules, injections and a syrup.

PMID- 1391084
TI  - Separation of reduced and oxidized glutathione in a pharmaceutical preparation by
      ion-interaction reversed-phase HPLC.
AB  - A new method is presented for the simultaneous determination of reduced and
      oxidized glutathione by ion-interaction reversed-phase HPLC with octylamine
      orthophosphate as the interaction reagent, 5-microns Spherisorb ODS-2 as the
      stationary phase and UV detection at 230 nm. Lower limits of detection of 2.50
      micrograms ml-1 have been achieved for both the oxidized and the reduced forms.
      The method has been applied in the analysis of a commercial pharmaceutical
      preparation.

PMID- 1391083
TI  - Reversed-phase liquid chromatography of the opioid peptides--2. Quantitative
      structure-retention relationships and isocratic retention prediction.
AB  - The ability of Snyder's theory of linear gradient elution to predict the starting
      isocratic reversed-phase LC conditions (k' = 4-10) for the opioid peptides was
      investigated. The errors in predicting the concentration of acetonitrile (phi)
      required to elute the peptides with a k' value of 4 were high, ranging from 13.5
      to 38.1%. At k' = 10 the errors were generally reduced to less than 20%. This
      analysis was repeated with the same peptides after conversion to their
      fluorescent 1-cyanobenz[f]isoindoles (CBIs) by reaction with naphthalene-2,3
      dicarboxaldehyde/cyanide. For the CBI derivatives, the errors in predicting the
      required concentration of acetonitrile for isocratic elution were markedly
      reduced and ranged from 0 to 14.3 for k' = 4 and 0 to 11.9% for k' = 10. The
      errors in the model in predicting the required isocratic mobile phase accurately
      were attributed to a mixed mechanism of retention involving solvophobic and
      silanophilic interactions and leading to non-linear relationships between log k'
      and phi. Even when the errors in predicting the required value of phi were
      relatively high, the Snyder approach was found to be very useful in predicting
      the initial starting conditions for the reversed-phase LC of the native opioid
      peptides as well as their fluorescence CBI derivatives.

PMID- 1391085
TI  - High-performance liquid chromatographic determination of nifedipine and a trace
      photodegradation product in hospital prescriptions.
AB  - A HPLC method is developed for the assay of nifedipine and trace amounts of a
      photodegradation product in pulverized tablets used in the preparation of
      hospital prescriptions. After liquid-liquid extraction, nifedipine and its
      photodegradation product are chromatographed using a reversed-phase system which
      involves UV detection at 254 nm and the use of two internal standards. The trace
      photodegradation product in pulverized tablets is determined along with
      nifedipine by the same procedure. The method is capable of determining 0.5-5.0
      micrograms of nifedipine using p-nitronifedipine as the internal standard and
      0.01-0.5 micrograms of the photodegradation product using 5-hydroxynifedipine as
      the internal standard. The standard error is found to not exceed 8.4%. The
      methods are useful for the study of the disposition or photostability of
      nifedipine in tablets and pulverized tablets.

PMID- 1391086
TI  - LC assay for salmon calcitonin in aerosol formulations using fluorescence
      derivatization and size exclusion chromatography.
AB  - A highly sensitive LC procedure was developed that utilizes fluorescence
      derivatization and detection coupled with size exclusion chromatography for the
      analysis of salmon calcitonin in salmon calcitonin aerosols. The LC procedure
      uses fluorescamine derivatization to label the primary amino groups of the
      peptide. The derivatization procedure is completely automated by an autosampler
      capable of pre-column mixing. Size exclusion chromatography is performed using a
      Supelco G2000 SWXL column. The method can be used to assay the amount of salmon
      calcitonin delivered per actuation of an aerosol unit. The procedure is simple,
      accurate, and precise and can detect as little as 2 ng ml-1 concentrations of
      salmon calcitonin.

PMID- 1391087
TI  - Identification of caprolactam as a potential contaminant in parenteral solutions
      stored in overwrapped PVC bags.
AB  - Semipreparative liquid chromatographic separation and subsequent off-line mass
      spectrometry have revealed caprolactam as a new contaminant in intravenous
      solutions. The content of the lactam was found to be 1.2-15.0 mg l-1 determined
      by liquid chromatography. Contamination is attributed to migration of caprolactam
      from the protecting plastic envelope through the PVC barrier and into the
      intravenous solution. Migration occurs during the final heat sterilization
      process.

PMID- 1391088
TI  - On-line determination and resolution of the enantiomers of ketoprofen in plasma
      using coupled achiral-chiral high-performance liquid chromatography.
AB  - High-performance liquid chromatography (HPLC) using a column-switching technique
      has been applied to the on-line determination and resolution of the enantiomers
      of ketoprofen (KPF) as an acidic model compound. The system incorporates a mobile
      phase conversion stage (LC-2), which has a dilution tube and a trapping column,
      between the achiral chromatography stage (LC-1) and the chiral chromatography
      stage (LC-3). KPF in plasma was separated from plasma components and was
      determined with the aid of an internal standard in LC-1. The eluate containing
      KPF was selectively transferred to LC-2, where the eluate was adequately diluted
      with a new mobile phase by using the dilution tube to reduce the influence of the
      mobile phase from LC-1, and KPF was reconcentrated on the trapping column. Then
      the KPF enantiomers were resolved in LC-3 after column-switching. This system is
      accurate and rapid compared with conventional HPLC. Very high sensitivity could
      be achieved with our system when a microbore ovomucoid column was employed in LC
      3. Incorporation of LC-2 allows the most favourable mobile phases for LC-1 and LC
      3 to be used independently. This method is greatly superior to usual column
      switching HPLC.

PMID- 1391089
TI  - An investigation of the effect of washing upon the morphine content of hair
      measured by a radioimmunoassay technique.

PMID- 1391090
TI  - Photolysis of cyanocobalamin in aqueous solution.
AB  - Cyanocobalamin is photolysed in aqueous solution to produce hydroxocobalamin. The
      kinetics of photolysis has been studied at pH 1-12 using a newly developed
      spectrophotometric method for the simultaneous determination of the two compounds
      at 550 and 525 nm or 361 and 351 nm. Cyanocobalamin follows zero-order kinetics
      at the pH values studied and the rate is catalysed by both hydrogen and hydroxyl
      ions. The log k-pH profile indicates that cyanocobalamin has maximum stability
      near pH 7. The cationic species appears to be more susceptible to photolysis than
      the neutral form. The rate constant for the reaction at pH 1 is 1.32 x 10(-7) mol
      l-1 min-1 compared with 0.050 x 10(-7) mol l-1 min-1 at pH 7.

PMID- 1391091
TI  - A flow injection method for the determination of oxalate in urine based on a
      promoting effect.

PMID- 1391093
TI  - An automatic data reduction and transfer method to aid pattern recognition
      analysis and classification of NMR spectra.
AB  - A method of automatically generating reduced NMR data and transferring it between
      computers is proposed. These data can then be used as descriptors for input to
      non-parametric statistical routines for classification of the samples.

PMID- 1391092
TI  - Radioimmunoassay for ubenimex in human serum.
AB  - Anti-ubenimex antibody was produced by immunization of rabbits with ubenimex
      bovine serum albumin (BSA) conjugate which was synthesized by coupling ubenimex
      directly to BSA using 1-ethyl-3-(3-dimethyl-aminopropyl)carbodiimide. The
      resulting antibody exhibited little cross-reactivity with p-hydroxyubenimex or
      (2S,3R)AHPA, (2S,3R)-3-amino-2-hydroxy-4-phenylbutanoic acid present in human
      serum as metabolites. Ubenimex in human serum could be measured selectively
      without prior drug extraction and purification. The standard curve prepared using
      the present assay method gave good linearity in the range 0.25-25 ng per assay
      tube. The detection limit was 125 pg per assay tube. The concentrations of
      ubenimex in human serum determined by the present method were in good agreement
      with those obtained by GC-SIM. The present method with its high sensitivity and
      specificity may be a valuable tool for the study of the pharmacokinetics of
      ubenimex.

PMID- 1391094
TI  - A selective and sensitive kinetic method for the determination of procaine and
      benzocaine in pharmaceuticals.
AB  - A simple stopped-flow method for the determination of procaine and benzocaine
      which is suitable for their routine analysis in pharmaceutical samples is
      reported. The method is based on a condensation reaction between each compound
      and 4-dimethylaminocinnamaldehyde, which yields coloured compounds and which are
      monitored spectrophotometrically. The calibration graph generated is linear over
      the range 0.5-20 micrograms ml-1 (RSD 0.73%) for procaine and 0.5-15 micrograms
      ml-1 (RSD 0.40%) for benzocaine, and the selectivity is very high in both cases.
      The proposed methods were satisfactorily applied to the determination of the two
      drugs in various pharmaceutical samples. A procedure for resolution of procaine
      benzocaine mixtures in mass ratios between 15:1 and 1:7 with a precision of ca 1%
      was developed in order to determine one compound in the presence of the other
      with no interference.

PMID- 1391096
TI  - Competitive binding assay for quantitative determination of GM1 ganglioside in
      plasma and cerebrospinal fluid.
AB  - A competitive binding assay for the quantitative determination of GM1 ganglioside
      is described. After extraction from biological fluids, GM1 was incubated with a
      known amount of cholera toxin B-subunit conjugated with horseradish peroxidase,
      and exposed to GM1 adsorbed onto polystyrene microwells. Since GM1 in solution
      blocks the binding of toxin B-subunit to GM1 adsorbed onto the solid phase,
      enzyme activity serves as a reciprocal measure of GM1 concentration in the
      sample. The assay was used to determine the basal level of GM1 in plasma and
      cerebrospinal fluid in different populations.

PMID- 1391095
TI  - Synthesis and analysis of O,O'-dicarboxylate (dibenzyl) bispilocarpates as
      possible prodrugs of pilocarpine.
AB  - As a part of a series of studies to develop prodrug derivatives of pilocarpine,
      the O,O'-succinyl (dibenzyl), O,O-adipoyl (dibenzyl), O,O-fumaryl (dibenzyl), and
      O,O-terephthaloyl (dibenzyl) bispilocarpate fumarates were synthesized as a new
      class of pilocarpine prodrugs. The compounds were prepared from pilocarpic acid
      benzyl monoester by coupling two pilocarpic acid benzyl monoesters together with
      spacer chains by usual esterification methods. Liquid chromatography, thermospray
      liquid chromatography-mass spectrometry, high-resolution mass spectrometry, and
      NMR spectroscopy were applied to the identification and the purity evaluation of
      the synthetic products.

PMID- 1391097
TI  - Fundamental studies in reversed-phase liquid-solid extraction of basic drugs; II:
      Hydrogen bonding effects.
AB  - Anomalies in the elution order of the beta-blockers atenolol and propranolol on
      reversed-phase liquid-solid extraction cartridges have been studied. The hydrogen
      bond acceptor properties of the polar ring substituent in atenolol was found to
      result in greater retention than would be expected from the reversed-phase or
      cation-exchange mechanisms alone. This hydrogen bonding interaction could be
      attenuated by inclusion of a strong hydrogen bond acceptor in the eluent or more
      successfully by increasing the eluent water content. The conclusions from this
      work have been used to explain previously reported anomalies in the solid-phase
      extraction of polar basic drugs.

PMID- 1391098
TI  - A safer methylation procedure with boron trifluoride-methanol reagent for gas
      chromatographic analysis of ritalinic acid in urine.
AB  - Ritalinic acid (RITA), the major metabolite of methylphenidate (Ritaline) is
      extracted with a solid-phase C8 column. Following elution, methylation of the
      carboxylic group is performed with boron trifluoride-methanol as a reagent. The
      methyl ester of RITA which structurally corresponds to the parent compound
      methylphenidate is reextracted at pH 9-11. Each step of the analytical method has
      been systematically studied, particularly the parameters governing the
      esterification reaction with BF3-methanol. The recovery from the overall method
      is 96%. The limit of detection is 0.05 micrograms ml-1 with GC-NPD for a 10-ml
      urine sample. The method has been successfully applied to the detection and
      quantitation of RITA in urine specimens. The specificity of the methylated RITA
      peak has been verified by GC-MS in scan mode. Use of diazomethane or sulphuric
      acid is thus replaced by the use of a less hazardous reagent.

PMID- 1391099
TI  - Ion trap detector--capillary gas chromatography of valproic acid and its mono
      unsaturated metabolites in serum using methyl ester derivatives.
AB  - A quantitative method was developed for valproic acid and five of its mono
      unsaturated metabolites using capillary gas chromatography-mass spectrometry with
      selected ion monitoring. The method was applied to serum and all metabolites were
      measured in a single run. Methyl esters were synthesized as the derivatives
      suitable for gas chromatography. Calibration curves were found to be linear and
      the sensitivities in the order of 0.1 micrograms ml-1. Patients' data are
      presented. By this method it is possible to separate the stereoisomers of 2-n
      propyl-2-pentenoic acid and of 2-n-propyl-3-pentenoic acid.

PMID- 1391100
TI  - Collaborative study of the analysis of chlortetracycline hydrochloride by liquid
      chromatography on polystyrene-divinylbenzene packing materials.
AB  - A previously established method for the analysis of chlortetracycline by liquid
      chromatography using polystyrene-divinylbenzene stationary phases was examined in
      a multicentre study involving four laboratories and a total of 12 columns. Three
      chlortetracycline hydrochloride samples were analysed. The main component and the
      impurities were determined. An analysis of variance, treating each column as a
      different laboratory, showed absence of consistent laboratory bias and presence
      of significant laboratory-sample interaction. Estimates for the repeatability and
      reproducibility of the method, expressed as relative standard deviations of the
      result of the determination of chlortetracycline hydrochloride, were calculated
      to be 0.7 and 1.2%, respectively. When the analysis of variance was performed
      using only the results obtained on the wide pore (1000 A) stationary phases, the
      laboratory-sample interaction strongly decreased. It is therefore proposed to use
      such materials for the analysis of chlortetracycline.

PMID- 1391101
TI  - Determination of sertaconazole nitrate, a new imidazole antifungal, by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatographic method is developed for the
      determination of bulk sertaconazole nitrate and related compounds (potential
      impurities and degradation products) as well as a sertaconazole nitrate cream
      formulation. A 10-microns Spherisorb CN column is used along with a mobile phase
      consisting of acetonitrile and aqueous 0.01 M sodium phosphate (37:63, v/v). The
      sertaconazole nitrate peak is monitored at a wavelength of 260 nm; the retention
      time being 19.3 min. The detector response for sertaconazole nitrate is linear
      over the concentration range from 64 to 96 micrograms ml-1. The method is found
      to be sufficiently selective for the reliable determination of related compounds,
      FI-7001, FI-7009 and FI-7011, as indicated by same-day and between-day relative
      standard deviations (RSD) for replicate assays of 1.72% (n = 9) and 2.17% (n =
      24), respectively. The application of this method to a cream formulation of
      sertaconazole nitrate is found to give a mean percentage recovery of 99.4% with
      RSD of 1.14% (n = 9); none of the cream vehicle peaks are found to interfere with
      the determination of sertaconazole nitrate.

PMID- 1391102
TI  - Chromatographic analysis of 1,3-bis(dimethylamino)isopropyl 4
      chlorophenoxyacetate dihydrochloride, a new CNS stimulant.
AB  - A reversed-phase liquid chromatographic method is developed for the assay of the
      new CNS stimulant, 1,3-bis(dimethylamino)isopropyl 4-chlorophenoxyacetate
      dihydrochloride (BCE-001), and its main contaminant, 4-chlorophenoxyacetic acid
      (PCPA). In the first place the possible reactions of BCE-001 with mobile phase
      components are investigated and it is found that BCE-001 is readily hydrolysed in
      water and undergoes transesterification in methanol or ethanol. The methyl ester
      is formed rapidly and quantitatively so that BCE-001 can be assayed as methyl 4
      chlorophenoxyacetate. PCPA is formed as a result of the hydrolysis of BCE-001
      during the sample pretreatment and chromatographic separation and this causes an
      overestimate of the PCPA impurity in the bulk drug. An effective method is
      developed to prevent the hydrolysis of BCE-001 during sample pretreatment.

PMID- 1391103
TI  - A study of chloroquine and desethylchloroquine plasma levels in patients infected
      with sensitive and resistant malaria parasites.
AB  - This study was carried out on 63 patients in the town of Gadaref in eastern
      Sudan; each patient was given the standard therapeutic dose of chloroquine (CQ).
      Plasma levels of chloroquine and its major metabolite desethylchloroquine (DCQ)
      were measured by means of a high-performance liquid chromatographic method (HPLC)
      in patients infected with sensitive (sensitive group) and resistant (resistant
      groups) strains of Plasmodium falciparum. The ratios of chloroquine to
      desethylchloroquine (CQ/DCQ) in different groups were calculated and the results
      obtained were compared and correlated with the degree of parasitaemia. The
      statistical analysis of the results showed that the plasma content of CQ and the
      CQ/DCQ ratio in the majority of the patients fall within the normal mode of
      distribution. A small group of patients showed a deviation from the normal mode
      by having a rather high CQ plasma level and a high ratio of CQ/DCQ. The mean
      plasma levels of CQ and the CQ/DCQ ratio in the sensitive group was found to be
      higher than that in the resistant groups. However, these differences were found
      to be not significant. Correlation tests showed that the levels of CQ and the
      CQ/DCQ ratios increase with the increase of the degree of parasitaemia in the
      sensitive group but decrease with the increase of parasitaemia in resistant
      groups.

PMID- 1391104
TI  - The validation of a radioimmunoassay for the quantification of eflumast in
      clinical samples.

PMID- 1391105
TI  - The determination of the enantiomers of halofantrine and monodesbutylhalofantrine
      in plasma and whole blood using sequential achiral/chiral high-performance liquid
      chromatography.

PMID- 1391106
TI  - 4-Bromomethyl-7-methoxycoumarin and analogues as derivatization agents for high
      performance liquid chromatography determinations: a review.
AB  - A major part of modern analytical problem solving deals with the trace level
      determination of organic compounds and contaminants in biomedical, food and
      environmental samples. In the analysis of these samples chromatographic
      techniques play a predominant role. Unfortunately, however, even the combined
      force of an efficient separation plus a sophisticated mode of detection does not
      always create sufficient selectivity and/or sensitivity for the final goal to be
      attained. In such cases, special attention has to be devoted to derivatization or
      conversion of the analyte(s) of interest (for improved detection selectivity
      and/or sensitivity) and sample pretreatment (for trace enrichment and clean-up).
      The above is especially true when, as is often the case today, relatively polar
      drugs, endogenous compounds, additives or environmental pollutants and/or their
      (bio)-degradation products have to be determined. For such classes of compounds
      high-performance column liquid chromatography (HPLC) generally is the preferred
      method of separation. Reversed-phase HPLC with fluorescence detection is a
      powerful means of analysis for compounds which possess native fluorescence. They
      are, however, relatively few in number. In order to make the method useful for a
      much wider range of analytes, one can therefore resort to derivatization
      (labelling) or other means of analyte conversion to obtain highly fluorescent
      reaction products, which can then be detected with the required selectivity and
      sensitivity. 4-Bromomethyl-7-methoxycoumarin is often used as fluorescent label
      for the determination of compounds possessing a carboxylic group. About 8% of the
      biologically interesting analytes--ranging from polar amino acids and peptides to
      apolar fatty acids--possess such a group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391107
TI  - [Hypocaloric peripheral parenteral nutrition in postoperative patients (Proyecto
      Europan)].
AB  - Hypocaloric peripheral parenteral nutrition (HPPN) appears to be indicated in
      patients with moderate malnutrition subjected to a short period of fasting
      following surgery. Our objective is to determine whether or not the intake of
      hypocaloric parenteral solutions containing aminoacid is useful in postsurgical
      patients, by means of a study of different nutritional evaluation parameters. A
      study was performed on 35 postsurgical patients who fulfilled at least 2 of the
      following criteria indicating malnutrition: 1) albumin levels less than 3 g/dl;
      2) prealbumin levels less than 21 mg/; 3) body weight less than 95% of ideal
      weight. The patients were divided into 3 groups: Group I consisted of 15 patients
      treated with conventional fluid therapy, Group II consisted of 10 patients
      treated with nutritional support based on glucose and aminoacid and Group III was
      comprised of 10 patients also treated with a nutritional therapy based on
      glycerol and aminoacid. The most significant data included a rapid recovery of
      short term proteins (prealbumin and retinol-binding protein) and a less negative
      nitrogen balance 5 days afterwards in both the glucose and glycerol groups, both
      of which were statistically significant. With regard to complications studied,
      there was a greater incidence of suture dehiscence in the control group than in
      the groups under treatment (13.3% compared to 50%). Our conclusion is that HPPN
      is a valid nutritional support measure in postsurgical patients in certain
      clinical situations and circumstances, although further controlled, randomized
      studies should be considered, during both the pre and post operative periods of
      these patients in order to clearly indicate how and when nutritional therapy
      should be applied.

PMID- 1391108
TI  - [Nickel content of parenteral nutrition solutions].
AB  - Determination of the nickel content in 49 commercial solutions used in parenteral
      nutrition, by means of atomic absorption spectroscopy in a graphite kiln.
      Important differences were found between the different components (less than 5 to
      23.000 ppb). The largest concentrations of Ni were found in sodium chloride,
      phosphate salts, 10% calcium chloride and 2M potassium chloride, whereas the
      aminoacid, glucose and lipid solutions contained the smallest concentrations. The
      amount of Nickel in the preparations varied depending on the supplier and
      different salts of the compound itself. The Nickel intake in 2 TPN solutions with
      high and low concentrations of Ni (827 and 270 micrograms respectively) was also
      analyzed, and this intake was higher than the estimated amount absorbed in the
      diet. In the case of the TPN with a high Nickel content, this was higher than the
      level detected as being the cause of sensitivity reactions in patients sensitive
      to Nickel.

PMID- 1391109
TI  - [Effect of total parenteral nutrition on bone metabolism].
AB  - Total parenteral nutrition (TPN) for a prolonged period of time can be associated
      with bone pain and osteomalacia. We performed a study on the phosphorus/calcium
      metabolism and serum levels of osteocalcin (BGP), a protein proposed as
      constituting the bone turnover index in 31 patients receiving TPN (age 57 +/- 14
      years, 22 males and 9 females) diagnosed as suffering from pathology of the
      digestive tract or geno-urinary pathology. The duration of the TPN was from 9.1
      +/- 6.6 days (range 2-31 days). We observed and increase of FA (178 +/- 101 U/l),
      with a significant decrease of BGP (2.2 +/- 2.0 ng/ml vs. 3.7 +/- 1.3 ng/ml in
      controls; p less than 0.001). Serum levels of phosphorus and calcium corrected
      according to proteins were within normal limits. Hypercalciuria was detected in
      the urine (328 +/- 278 mg/24 hours), and phosphaturia (607 +/- 522 mg/24 hours).
      Based on the BGP results, we can conclude that patients subjected to TPN for a
      short period of time undergo a decrease in bone turnover.

PMID- 1391112
TI  - Differentiation of linearly correlated noise from chaos in a biologic system
      using surrogate data.
AB  - Experimental time-series of human H-reflexes were analyzed for the presence of
      fractal structure or deterministic chaos. Surrogate data sets consisting of
      stochastic time-series with preservation of selected properties of the
      experimental time-series were used as mathematical controls. Artifacts generated
      during the analysis of the experimental data are identified, and shown to be due
      to linear correlation in the original time-series. The method is simple and
      generally applicable to the non-linear analysis of time-series from any
      experimental system.

PMID- 1391110
TI  - [Epidemiology of parenteral nutrition during 5 years of follow-up by a nutrition
      team].
AB  - The purpose of this retrospective study is to ascertain the physiopathological
      characteristics of patients on parenteral nutrition (PN), the types of diet used
      and duration of treatment. Presentation of epidemiological results and evolution
      of 637 adults receiving PN after a five-year period of nutritional follow-up,
      conducted by a Nutrition Team (NT) in hospital. For the purpose of this study, we
      used the Follow-Up charts of all the patients treated with PN from 1986-1990. The
      results obtained lead us to affirm that most patients suffered a malignant
      gastrointestinal process, that the duration of the PN was reduced significantly
      during the five-year term, mainly using dietary protocols, and that there was a
      gradual increase in preparations of nutrient units subjected to controls compared
      to the total prepared by the Pharmacy Department.

PMID- 1391111
TI  - [Nutritional support in laryngectomized patients].
AB  - Pathologies involving tumours of the neck are an important group of neoplasias.
      The tumours themselves are often the cause of malnutrition, and this may be
      aggravated in these patients by other factors such as: excess of alcohol and
      cigarettes, anatomical location of the tumour next to the digestive tract and the
      application of cyto-reducing treatment applied previously. The main purpose of
      the present study is to analyze the possible effect of hospital diets during the
      postoperative period in laryngectomized patients, on the development of
      malnutrition. For this purpose 49 patients were studied, all diagnosed
      consecutively during the last year as suffering from epidermoid carcinoma of the
      larynx, subjected to 24 total laryngectomies, 4 partial laryngectomies and 21
      supraglottic laryngectomies. A conventional diet was administered at random to 21
      patients, and a commercial enteral diet to the remaining 28. The most important
      conclusions were as follows: a) high incidence of harmful habits, b) positive
      nutritional state of the patients upon admittance, c) high incidence of
      malnutrition one week after the operation, which was maintained virtually in the
      same proportion to the time spent in hospital, d) the lack of influence of the
      nutritional state by type of diet administered, e) the possible influence on
      malnutrition by type of surgery performed, location of the tumour (pyriform
      sinus) and high incidence of complications usually developed.

PMID- 1391113
TI  - Evidence for a generalized Laguerre transform of temporal events by the visual
      system.
AB  - It is generally assumed that the early visual processing is constituted by a set
      of filters operating in parallel. In this respect the visual system performs a
      transform, generating a code of the characteristics of the input signal.
      Recently, it has been suggested that the coding of the spatial characteristics by
      the visual system can be described by a Hermite transform (Martens, 1990a, b). It
      was also suggested that a three-dimensional Hermite transform can be used to code
      spatiotemporal events. In contrast to this latter suggestion, we argue that the
      coding of temporal events takes the form of a generalized Laguerre transform. We
      review psychophysical evidence supporting this hypothesis.

PMID- 1391114
TI  - Disambiguating ambiguous figures by a model of selective attention.
AB  - Ambiguous figures are visual stimuli which are interpreted multiply by the human
      visual system. A model is proposed which disambiguates the ambiguous figures. The
      model was formulated based on the characteristics of visual information
      processing, accompanied with selective attention. In the ambiguous figure "my
      husband and my father-in-law", it was necessary to simulate visual information
      processing so that attention was directed to the multiple features in the figure
      to disambiguate the ambiguous figure. Pictures, obtained from the model, were
      examined as to whether they were interpreted unambiguously or not. Results show
      that the model, simulated selective attention, can disambiguate the ambiguous
      figures. This suggests that the image per se, viewed through selective attention,
      becomes unambiguous before the figure is interpreted in the higher level. Results
      also show that the computer simulation of selective attention would make it
      possible to examine factors affecting the initial interpretation of the figure.

PMID- 1391115
TI  - Reduction of a Hodgkin-Huxley-type model for a mammalian neuron at body
      temperature.
AB  - Hodgkin-Huxley-type models mimic the electrical behavior of excitable membranes
      quite realistically. However, inclusion of many different ionic channels into
      such a model yields a highly complex set of differential equations. In this paper
      a reduction of a "full" Hodgkin-Huxley-type model based on voltage-clamp data
      from small rat neurons in the supraoptic nucleus area is introduced. It was found
      that two of the ionic channel gating variables of the full model preserved a
      rather close relationship during simulations. This allowed to express one of
      these gating variables in terms of the other one thus reducing the number of
      differential equations the model is based on. The behavior of the reduced model
      was very similar to that of the full model. In particular, important
      physiological features as spike shape and constant-input-to-interspike-interval
      relationship were (almost) identical in the full and the reduced model.

PMID- 1391116
TI  - Unsupervised clustering and centroid estimation using dynamic competitive
      learning.
AB  - In this paper, an unsupervised learning algorithm is developed. Two versions of
      an artificial neural network, termed a differentiator, are described. It is shown
      that our algorithm is a dynamic variation of the competitive learning found in
      most unsupervised learning systems. These systems are frequently used for solving
      certain pattern recognition tasks such as pattern classification and k-means
      clustering. Using computer simulation, it is shown that dynamic competitive
      learning outperforms simple competitive learning methods in solving cluster
      detection and centroid estimation problems. The simulation results demonstrate
      that high quality clusters are detected by our method in a short training time.
      Either a distortion function or the minimum spanning tree method of clustering is
      used to verify the clustering results. By taking full advantage of all the
      information presented in the course of training in the differentiator, we
      demonstrate a powerful adaptive system capable of learning continuously changing
      patterns.

PMID- 1391117
TI  - A coupled pacemaker-slave model for the insect photoperiodic clock:
      interpretation of ovarian diapause data in Drosophila melanogaster.
AB  - A coupled circadian oscillator model for the insect photoperiodic clock is
      described which consists of a hierarchically arranged pacemaker and slave. The
      pacemaker is self-sustained, temperature compensated, and entrainable by the
      light cycle; the slave is a damping oscillation receiving entrainment from two
      sources, from the pacemaker via a coupling factor, and also directly from the
      light. The damping slave oscillation is seen as the "photoperiodic oscillator",
      equivalent to that proposed earlier by Lewis and Saunders (1987). The present
      simulations describe the effect of the strength of the coupling factor between
      hypothetical short- and long-period pacemaker oscillations (modelled on the
      "clock" mutants perS and perL2 in Drosophila melanogaster) and a slave
      oscillation with a period of about 24 hours. The output is presented in terms of
      photoperiodic response curves and Nanda-Hamner, or resonance, plots. With a high
      coupling strength, the pacemakers strongly entrain the slave, but with a low
      coupling strength the slave's properties are more evident. The model is presented
      as a possible explanation for recent ovarian diapause data in D. melanogaster
      "clock" mutants (Saunders 1990), but also as a more general model for the role of
      the insect circadian system in seasonal time measurement.

PMID- 1391118
TI  - Two and three dimensional reductions of the Hodgkin-Huxley system: separation of
      time scales and bifurcation schemes.
AB  - We study two different two-dimensional reductions of the Hodgkin-Huxley
      equations. We show that they display the same qualitative bifurcation scheme as
      the original equations but overestimate the current range where periodic emission
      occurs. This is essentially due to the assumption that the evolution of the
      sodium activation variable m is instantaneous with respect to the dynamics of the
      variables h and n, an hypothesis that breaks down at high values of the injected
      current. To prove this point we compare the current-amplitude relation, the
      current-frequency relation, and the shapes of individual spikes for the two
      reduced models to the results obtained for the original Hodgkin-Huxley model and
      for a three-dimensional model with instantaneous sodium activation. We show that
      a more satisfying agreement with the original Hodgkin-Huxley equations is
      obtained if we modify the evolution equation for the potential by incorporating
      the prominent features of the dynamics of m.

PMID- 1391119
TI  - Information maintenance and statistical dependence reduction in simple neural
      networks.
AB  - This study compares the ability of excitatory, feed-forward neural networks to
      construct good transformations on their inputs. The quality of such a
      transformation is judged by the minimization of two information measures: the
      information loss of the transformation and the statistical dependency of the
      output. The networks that are compared differ from each other in the parametric
      properties of their neurons and in their connectivity. The particular network
      parameters studied are output firing threshold, synaptic connectivity, and
      associative modification of connection weights. The network parameters that most
      directly affect firing levels are threshold and connectivity. Networks
      incorporating neurons with dynamic threshold adjustment produce better
      transformations. When firing threshold is optimized, sparser synaptic
      connectivity produces a better transformation than denser connectivity.
      Associative modification of synaptic weights confers only a slight advantage in
      the construction of optimal transformations. Additionally, our research shows
      that some environments are better suited than others for recording. Specifically,
      input environments high in statistical dependence, i.e. those environments most
      in need of recoding, are more likely to undergo successful transformations.

PMID- 1391120
TI  - Gamma/delta receptor-expressing T-cell clones from a cutaneous T-cell lymphoma
      suppress hematopoiesis.
AB  - Recently we described a cutaneous T-cell lymphoma expressing the gamma/delta T
      cell receptor [5]. The patient suffering from this lymphoma showed low numbers of
      myeloid and T cells in peripheral blood, while B and NK cells were relatively
      increased. In vitro culture of the patient's bone marrow (BM) cells revealed a
      significant suppression of myeloid/monocyte colony formation (GM-CFU) compared
      with normal controls. This was not due to infiltration of the BM with lymphoma
      cells. We speculated that a soluble factor either secreted or induced by the
      lymphoma cells might be responsible for the marked suppression of hematopoiesis
      in this patient. From a skin biopsy with infiltrating gamma/delta T-lymphoma
      cells we established T-cell clones bearing the gamma/delta T-cell receptor and
      resembling the phenotype of the lymphoma cells. The supernatant (SN) of these
      gamma/delta T-cell clones reduced the number of colonies in a CFU-GM assay (using
      normal control BM) in comparison to SN of alpha/beta T-cell clones established
      from the same biopsy. This suppression was seen mainly on day 7 of culture and
      was not neutralized by the addition of placenta-CM. The main mediator of this
      suppression seems to be IFN-gamma, since it was detectable in high amounts in the
      SN of these gamma/delta T-cell tumor clones as well as in the serum of the
      patient. In addition, anti-IFN-gamma antibodies can reverse the T-cell SN
      mediated suppression of CFU-GM. We conclude that high serum levels of interferon
      gamma, which is secreted in high amounts from gamma/delta T-cells grown from a
      biopsy of a cutaneous lymphoma, can suppress hematopoiesis.

PMID- 1391121
TI  - All-trans retinoic acid in acute promyelocytic leukemia: preliminary results in
      Cuba.
AB  - Seven patients with acute promyelocytic leukemia (APL) were treated with all
      trans retinoic acid (ATRA). Five (71.4%) achieved complete remission (CR). Most
      side effects were transient and well tolerated. Hyperleukocytosis was the major
      adverse effect. These observations confirm the efficacy of ATRA for inducing CR
      in APL.

PMID- 1391122
TI  - Oxidative damage of erythrocytes infected with Plasmodium falciparum. An in vitro
      study.
AB  - The extent of reduced glutathione, activity of glutathione peroxidase, amount of
      membrane lipid peroxidation products, and the extent of hemoglobin release from
      host erythrocytes during in vitro Plasmodium falciparum growth was studied.
      Highly synchronized parasite cultures were studied to examine the alterations
      caused by different growth stages of the parasite. There was a moderate increase
      in the reduced glutathione content as the parasite matured, which was significant
      only in schizont-rich erythrocyte lysates (p < 0.05) whereas the activity of
      glutathione peroxidase was significantly low in all the parasitized red blood
      cells (ring-infected RBC, p < 0.005; trophozoite- and schizont-infected RBC, p <
      0.001). The lipid peroxidation product, malonyldialdehyde, of the host red cells
      increased gradually to more than fourfold in schizont-rich cells as compared with
      normal erythrocytes (p < 0.001). The hemoglobin release from cultured cells was
      significantly higher in all parasitized red cell cultures as well as in
      uninfected cells kept in in vitro, as compared with normal erythrocytes. The
      consequence of such changes induced by the malarial parasites in the host red
      cells in the pathogenesis of erythrocyte destruction and anemia of P. falciparum
      malaria is discussed.

PMID- 1391123
TI  - Platelet heterogeneity based on lactic dehydrogenase activity.
AB  - Mean lactic dehydrogenase (LDH) activity of human platelets is about 5
      nU/platelet; expressed on a cell volume basis, it is 0.5 nU/fl. Platelet
      separation by means of centrifugation on a Percoll discontinuous gradient gives
      different subpopulations with a clear-cut change of LDH at a mean platelet volume
      (MPV) of about 6 fl. The LDH content of platelets with a MPV > 6 fl is constant
      (about 0.5 nU/fl), while that of small platelets (3 < MPV < 6 fl) is inversely
      correlated with the MPV and reaches a value of 1.5-2.0 nU/fl. Because small
      platelets are granule-depleted, we suggest that platelet LDH activity be
      considered as an in vivo activation index.

PMID- 1391124
TI  - Histoplasmosis in hairy cell leukemia: case report and review of the literature.
AB  - Progressive disseminated histoplasmosis (PDH) has been described in only six
      patients with hairy cell leukemia (HCL). Herein we describe an additional patient
      with HCL and disseminated histoplasmosis. Additionally, we note that three of
      seven cases of disseminated histoplasmosis and HCL have occurred in East Texas.
      PDH is to be suspected in febrile HCL patients in an endemic area who fail to
      respond to antibacterial therapy. We emphasize that serologic studies are useful
      in the diagnosis of PDH in HCL patients, and these patients respond well to
      therapy.

PMID- 1391125
TI  - Secondary acute lymphoblastic leukemia with t (4;11): report on two cases and
      review of the literature.
AB  - We report two cases of secondary acute lymphoblastic leukemia (ALL) with t (4;11)
      (q21;q23) translocation occurring after chemotherapy and radiotherapy for a prior
      cancer. Seven previously published cases of secondary ALL with t (4;11) (q21;q23)
      are also reviewed. Most patients had received a combination of topoisomerase II
      inhibitors (anthracyclines, mitoxantrone, or the epipodophillotoxin derivatives
      VP16 or VM26) and cyclophosphamide, which have also been implicated in the
      pathogenesis of secondary acute myeloid leukemia (AML) with 11q23 rearrangements.
      These observations give further support to the existence of a subgroup of
      secondary acute leukemias with cytogenetic findings "specific" for de novo ALL
      and AML, especially those with translocations involving the 11q23 region.

PMID- 1391126
TI  - A 72-year-old woman with fever and diffuse intravascular coagulation.

PMID- 1391127
TI  - Health and demographic characteristics of twin births: United States, 1988.
AB  - National trends in twin birth incidence by race of child are analyzed for the
      period 1950-88. Also reviewed are maternal and infant health and demographic
      characteristics associated with twin delivery for the year 1988.

PMID- 1391128
TI  - Vegetarians and longevity: imagining a wider reference population.

PMID- 1391129
TI  - Epidemiology in central and eastern Europe.

PMID- 1391130
TI  - Mortality pattern of German vegetarians after 11 years of follow-up.
AB  - A cohort of 1,904 vegetarians and persons leading a health-conscious life-style
      in the Federal Republic of Germany was identified in 1978. After a follow-up of
      11 years, mortality from all causes was reduced by one-half compared with the
      general population [the standardized mortality ratio (SMR) was 0.44 for men, 0.53
      for women]. Among the 858 men, 111 deaths were observed, with 255 expected; among
      the 1,046 women, 114 deaths were observed, with 215 expected. The lowest
      mortality was found for cardiovascular diseases (SMR = 0.39 for men, 0.46 for
      women); in particular, for ischemic heart diseases, mortality was reduced to one
      third of that expected. Cancer mortality was reduced by one-half in men (SMR =
      0.48), but only by one-quarter in women (SMR = 0.74). The deficit in cancer
      deaths was mainly observed for lung cancer and gastrointestinal cancers in males
      and for gastrointestinal cancers in females. Deaths from diseases of the
      respiratory and digestive systems were also reduced by about 50%. An excess of
      deaths occurred only for anemia. When the strict and the moderate vegetarians
      were analyzed separately, the strongest differential was found for ischemic heart
      diseases, which were much less frequent among strict vegetarians for both sexes.
      Some nondietary factors, such as higher socioeconomic status, virtual absence of
      smoking, and lower body mass index, may also have contributed to the lower
      mortality of the study participants.

PMID- 1391131
TI  - Dietary trace elements and esophageal cancer mortality in Shanxi, China.
AB  - To explore the relation between esophageal cancer and dietary trace elements in
      humans, we estimated the average daily intake of zinc, copper, iron, selenium,
      molybdenum, silicon, cadmium, and nickel in 21 Chinese communes, where the annual
      mortality rate from esophageal cancer among the population 30 years of age and
      over ranged from 0 to 495/100,000 person-years. We also estimated the relative
      level of calcium consumption. Zinc and copper intake were inversely related to
      esophageal cancer mortality, and calcium intake levels was positively related to
      esophageal cancer mortality. The predicted esophageal cancer mortality among a
      vegetarian population with a high level of dietary calcium and a low level of
      dietary zinc was 5.3 times as high as that in a vegetarian population with a low
      level of dietary calcium and a high level of dietary zinc. The influence of a
      high level of dietary calcium in a vegetarian population may be explained by a
      reduction in the absorption of dietary zinc.

PMID- 1391132
TI  - The association of waterborne chloroform with intrauterine growth retardation.
AB  - The potential reproductive effects of long-term, low-dose exposure to chloroform
      have received little attention despite the known, acute toxicity of high
      exposures and the wide-spread occurrence of low concentrations in drinking water.
      We studied the association of waterborne chloroform with low birthweight (less
      than 2,500 gm), prematurity (less than 37 weeks gestation), and intrauterine
      growth retardation (less than 5th percentile of weight for gestational age).
      Cases were not mutually exclusive, but each outcome was analyzed independently.
      Birth certificates from January 1, 1989, to June 30, 1990, were used to identify
      cases and randomly selected controls. All were live, singleton infants born to
      non-Hispanic, white women from Iowa towns with 1,000-5,000 inhabitants. Exposures
      to chloroform and other trihalomethanes were ecologic variables based on maternal
      residence and a 1987 municipal water survey. After adjustment for maternal age,
      parity, adequacy of prenatal care, marital status, education, and maternal
      smoking by multiple logistic regression, residence in municipalities where
      chloroform concentrations were greater than or equal to 10 micrograms/liter was
      associated with an increased risk for intrauterine growth retardation (odds ratio
      = 1.8, 95% confidence interval = 1.1-2.9). The major limitations of this study
      involve the ascertainment and classification of exposures to trihalomethanes,
      including such issues as the imprecision of using aggregate municipal measures
      for classifying exposure at the level of the individual, the potential
      misclassification due to residential mobility, and the fluctuation of
      trihalomethane levels.

PMID- 1391133
TI  - Oral contraceptives and premenopausal bilateral breast cancer: a case-control
      study.
AB  - We estimated the effect of oral contraceptive (OC) use on premenopausal bilateral
      breast cancer in a matched case-control study. One hundred forty-four cases were
      identified from population-based registries of Los Angeles County, California,
      and of Connecticut and from the major hospitals in Montreal and Quebec City.
      Matched controls were the unaffected sisters of the cases. When age was included
      in the model, ever-use of OCs for 1 year or more was associated with an odds
      ratio 1.7 (95% confidence interval = 1.0-2.9). The odds ratios associated with 1
      2, 3-6, and 7 years of use were 1.2 (0.61-2.4), 2.5 (1.2-5.3), and 2.0 (0.93
      4.2), respectively. Too few women had used OCs before their first full-term
      pregnancy or before age 25 for these estimates to be informative. Restricting the
      analyses to women who had ever given birth yielded an odds ratio for ever-use of
      OCs of 2.1 (1.0-4.4). The results indicate an increased risk of premenopausal
      bilateral breast cancer associated with OC use.

PMID- 1391134
TI  - Notes on the assessment of trend in the presence of nondifferential exposure
      misclassification.
AB  - Estimation of overall linear trend and statistical tests for trend are commonly
      applied in epidemiologic studies to evaluate the association between ordinal
      exposure variables and dichotomous health outcomes. In the discussion of these
      studies, the assertion is commonly made that the observed trends can only be
      conservative and reported P-values can only be too high owing to the occurrence
      of exposure misclassification that is supposed to be nondifferential, that is,
      unrelated to the health outcome of interest. This paper illustrates that this
      assertion is not generally justified without additional sensitivity analyses.
      Overestimation of trends and an erroneous reduction of P-values due to
      nondifferential exposure misclassification are unlikely, but not impossible, for
      monotonic exposure-disease associations. These may be common occurrences,
      however, if the observed exposure-disease association is nonmonotonic.

PMID- 1391136
TI  - Dichotomizing continuous outcome variables: dependence of the magnitude of
      association and statistical power on the cutpoint.
AB  - Dichotomizing a continuous outcome variable casts that variable in traditional
      epidemiologic terms (that is, disease, no disease). One consequence is overall
      reduced statistical power. A more fundamental concern is that the magnitude of
      various measures of association (for example, prevalence ratio, odds ratio) and
      statistical power depend on the cutpoint used to dichotomize the variable. The
      phenomenon is illustrated with a hypothetical situation assuming a two-level
      predictor variable and a normally distributed outcome variable. As the cutpoint
      is increased from lower to higher values, the prevalence ratio increases
      steadily, the odds ratio is described by a U-shaped curve, and statistical power
      is described by an inverted U-shaped curve. Furthermore, the extent of these
      effects depends on the difference between the means of the continuous outcome
      variable for the two levels of the predictor variable. An empirical example is
      given using data on education and blood pressure (dichotomized to create a high
      blood pressure vs low blood pressure variable). Except at each end of the
      distribution, the results follow the hypothetical example. The observation has
      implications for public health and medical treatment; different cutpoints should
      be examined to determine the optimal cutpoint in terms of policy and/or treatment
      decisions. The observation described here also has implications for statistical
      interpretation; statements about the magnitude of association or statistical
      significance have limited meaning unless both the cutpoint and the distribution
      of the outcome variable are specified.

PMID- 1391135
TI  - Preterm birth subtypes among blacks and whites.
AB  - The differences in preterm birth between blacks and whites are poorly understood.
      Our study examined subtypes of moderately preterm delivery (34-36 completed weeks
      of gestation) and very preterm delivery (20-33 weeks) in blacks and whites using
      North Carolina birth certificate data for 1988-1989. We divided the causes of
      preterm birth into three categories: preterm premature rupture of the membranes,
      indication of pregnancy complication, and idiopathic preterm deliveries. The
      overall prevalence of preterm birth was 8.0% and 16.7% for whites and blacks,
      respectively. The entire gestational age distribution of blacks was shifted to
      earlier ages relative to whites. More highly educated blacks still had higher
      risks of moderately and very preterm deliveries than less educated whites.
      Multivariate analysis, controlling for other factors, showed that blacks had 3.3,
      2.5, and 3.5 times the risk of whites to have preterm premature rupture of the
      membranes, complication-related, and idiopathic delivery, respectively, among
      very preterm births, and 1.6, 1.9, and 2.0 times the risk of whites for
      moderately preterm births of the same three types.

PMID- 1391137
TI  - Exact stratification of person-years.
AB  - This paper describes methods for the exact assignment of person-years of follow
      up to strata of time-dependent factors. It reviews methods applicable to
      variables that directly measure the passing of time and that increase in step
      with follow-up (monotonic time factors), and it extends their use to nonmonotonic
      time factors. When the same categorization scheme is used for all time factors
      (for example, 5-year categories), the follow-up period consists of segments whose
      length and position in time are predictable. A new exact method presented here
      uses this property to improve the efficiency of computations. The new method is
      generally faster than a method previously described. Finally, the paper outlines
      a method of exact person-year stratification that is applicable to all time
      dependent factors.

PMID- 1391138
TI  - Confidence limit analyses should replace power calculations in the interpretation
      of epidemiologic studies.
AB  - Frequently, after an epidemiologic study is completed, statistical power to
      detect a relative risk of interest is recalculated using data obtained during the
      course of the study. A negative study may then be dismissed on the grounds that
      its power was too low. However, post hoc power calculations ignore the actual
      relative estimate and its variance, which are by then known. We present evidence
      that post-study power calculations have little value and should be replaced by a
      more informative method using the upper (1 - alpha)% confidence limit of the
      point estimate that touches the value of the relative risk of interest.

PMID- 1391139
TI  - Confidence interval estimation of interaction.
AB  - Relative excess risk due to interaction, the proportion of disease among those
      with both exposures that is attributable to their interaction, and the synergy
      index have been proposed as measures of interaction in epidemiologic studies.
      This paper presents the methodology for obtaining confidence interval estimates
      of these indices utilizing routinely available output from multiple logistic
      regression software.

PMID- 1391140
TI  - The effects of nondifferential confounder misclassification in ecologic studies.
AB  - In ecologic studies, covariate levels of groups are often quantified as the
      prevalence of a dichotomous covariate. We show that, under certain conditions,
      nondifferential misclassification of such a binary covariate does not reduce the
      ability to control confounding by the covariate in ecologic studies. Thus, any
      remaining exposure-disease association in an adjusted ecologic analysis cannot be
      ascribed to incomplete control for confounding due to nondifferential
      misclassification of the dichotomy under those conditions, although residual
      confounding by the underlying covariate may still be present. This point is
      illustrated by ecologic analyses of the association between population density
      and mortality from lung cancer in women in 30 administrative districts of the
      Federal Republic of Germany, in which control for cigarette smoking is required.

PMID- 1391142
TI  - Cancer epidemiology in the former Soviet Union.
AB  - Cancer epidemiology in the former USSR is predominantly descriptive and depends
      heavily on cancer registration. Cancer epidemiologists have spent most of the
      last 35 years "correcting" the serious inconsistencies in reported incidence
      data, as official cancer statistics are notoriously incomplete and inaccurate.
      Professional standards of Soviet cancer epidemiologists reflect the prevailing
      conditions they have worked in, notably, severe censorship, bans on publishing,
      lack of computers for compilation of data or analysis, loose recordkeeping
      practices in institutions, restricted access to scientific literature, and
      limited opportunities for training in biostatistics and epidemiology. In the eyes
      of a new generation of young scientists, modern epidemiology is not an attractive
      discipline. Despite having one of the largest and most diverse populations in the
      world, the scientific productivity of ex-Soviet cancer epidemiologists is small.
      The increasing number of publications from the former USSR in international
      journals and of ongoing projects is an encouraging sign that cancer epidemiology
      in the republics that comprised the Soviet Union may be emerging from its
      prolonged infancy. Prospects depend on the ability of researchers to weather
      current economic and political disturbances.

PMID- 1391141
TI  - Risk factors for cardiovascular disease predict the development of diabetes among
      Utah families.
AB  - In 1989, we sent a medical follow-up questionnaire to 2,728 members of 98 Utah
      families originally screened from 1980 to 1983 in the Cardiovascular Genetics
      Research Clinic. The response rate was 69.9%. Of 1,134 nondiabetic individuals
      initially age 18 or older who returned the questionnaire, 10 were found to be
      newly diagnosed with diabetes. The incidence of diabetes was higher among
      individuals who were found at baseline to have central obesity, lipid
      abnormalities, especially increased triglyceride levels, and hypertension. Family
      histories of coronary heart disease and diabetes were not related to the
      development of diabetes. Our findings that cardiovascular disease risk factors
      predict the development of diabetes in this relatively young, Caucasian
      population are consistent with the results of studies from several different
      populations.

PMID- 1391143
TI  - Synergism between occupational arsenic exposure and smoking in the induction of
      lung cancer.

PMID- 1391144
TI  - [Cisapride and sucralfate in dyspepsia associated with duodenogastric reflux
      gastritis].
AB  - The present investigation was undertaken with the aim of evaluating the clinical
      efficacy on dyspeptic symptoms associated with duodenogastric reflux gastritis of
      two drugs belonging to two different groups: a prokinetic (cisapride) and a
      cytoprotective agent (sucralfate). A total of 18 patients with duodenogastric
      reflux gastritis diagnosed on the basis of symptoms, endoscopy and histology were
      studied. Nine were given 30 mg of cisapride/daily and 9 4 g of sucralfate/daily
      for two months according to a randomization list. Pyrosis, epigastric pain, sense
      of epigastric repletion and foul-tasting mouth were considered on a scale from 0
      to 4 attributed by the patient. The total score of dyspeptic symptoms
      significantly decreased only after cisapride (p less than 0.05). Considering each
      symptom alone, neither cisapride or sucralfate were able to significantly improve
      them. Cisapride seems to the better than sucralfate in improving dyspeptic
      symptoms associated with duodeno-gastric reflux gastritis.

PMID- 1391145
TI  - [Effects of the administration of magnesium hydroxide on gastric acidity in
      health volunteers].
AB  - Antacids are often the first therapeutic approach in patients with pyrosis. We
      carried-out a study on 8 healthy volunteers who underwent a 24 hour gastric pH
      metry to assess the real efficacy of magnesium hydroxide administration on
      gastric acidity. Magnesium hydroxide was alternatively administered at different
      dosages (400 mg or 800 mg) in the population studied. Our results showed a mild
      and non reproducible response to lower dose, but, on the contrary, the 800 mg
      dose always induced an immediate, effective and prolonged antacid action,
      reaching a maximum pH value of 5 and lasting up to 40 minutes. Our study
      confirms, using a modern and reliable technique as the 24-hour gastric pH-metry,
      the antacid activity of magnesium hydroxide.

PMID- 1391147
TI  - [Gastropathy caused by portal hypertension: a recently defined anatomo-clinical
      entity].

PMID- 1391146
TI  - [Enteral nutrition in the elderly].
AB  - Elderly is particularly at risk of malnutrition: he is not able to feed himself
      adequately, it is then important to attain correct intakes using also artificial
      enteral nutritional techniques (nasogastric tube, gastrostomy, etc.). These
      techniques may lead to complications (ab ingestis pneumonia, metabolic
      complications, alvus disorders): the use of artificially nutrition in the elderly
      must be carefully evaluated. 257 patients (M = 180, F = 77) aged 65 or more,
      mainly affected by neoplastic diseases (n 195) and by neurological and vascular
      diseases (n 62). The feeding route were evaluated in this study: 74% by
      nasogastric tube, 13% by gastrostomy, 11% by jejunostomy. In a group of 55
      patients similar concerning clinical and nutritional conditions we evaluated at
      the beginning of enteral feeding and four months later, caloric/protein intake,
      body weight and plasmatic albumin. In patients fed by nasogastric tube a mean
      intake of 1300 +/- 365 Kcal n.p./die, with a protein rate of 58.5 +/- 16.9 g/die
      was attained; by gastrostomy 1450 +/- 324 Kcal n.p./die and 65.5 +/- 16 g/die; by
      jejunostomy 1219 +/- 398 Kcal n.p./die and 53.3 +/- 21 g/die. The compliance to
      enteral nutrition was well in 37% of patients night administration was performed.
      Clinical complications: nausea and vomiting were observed in 9 patients with
      nasogastric tube, in 1 patient with gastrostomy and in 3 patients with
      jejunostomy; diarrhea has been noticed in 6 patients with nasogastric tube and in
      1 patient with jejunostomy. Mechanical complications; nasogastric tube (n 189):
      35 displacements, 7 breakages, 4 obstructions; pharyngostomy (n 6): 2
      displacements and 1 obstruction; gastrostomy (n 33): 3 displacements; jejunostomy
      (n 29): 2 misplacements.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391148
TI  - [Instrumental diagnosis in chronic inflammatory intestinal diseases].

PMID- 1391149
TI  - [Chief cell mass in gastric ulcer: cyto-secretory correlations].
AB  - The aim of this experience has been to evaluate the chief cell mass and serum
      pepsinogen I in gastric ulcer patients. Comparisons were also made with parietal
      cell mass and acid secretion. Chief cell mass and serum pepsinogen I are not only
      influenced by the localization of ulcer but, also, by the histological condition
      of fundic mucosa. In fact, the behaviour of serum pepsinogen I and chief cell
      mass in type I gastric ulcer is the same observed in case of fundic chronic
      gastritis without gastric ulcer. In case of gastric ulcer type I with superficial
      fundic gastritis it emerges normozymogenism with hyperpepsinogenemia++ I, with
      preatrophic fundic gastritis hypozymogenism with normopepsinogenemia, with
      atrophic fundic gastritis hypozymogenism with hypopepsinogenemia I. In type II
      and III gastric ulcer the chief cell mass and serum pepsinogen I behaviour as
      they do in duodenal ulcer with hyperpepsinogenemia although hypozymogenism is
      present.

PMID- 1391151
TI  - Playing the numbers game: Australia's health goals and targets.

PMID- 1391150
TI  - Aboriginal health research and the National Aboriginal Health Strategy.

PMID- 1391152
TI  - Historical trends in road accident types, deaths and casualties in Western
      Australia.
AB  - Road accident casualties are major consumers of health service resources in
      Australia, using inpatient care, accident and emergency treatment and other
      facilities. We analysed hospitalisations resulting from road accidents in Western
      Australia from 1968 to 1987 to examine trends in accident types, deaths and
      casualties. Data from the Western Australian Health Department's Hospital
      Morbidity System were used. Although hospitalisations from road accidents
      generally decreased, they were still higher than the Australian average in 1985.
      The rate of decline in hospitalisations was similar to that for fatalities and
      was not generally related to age or sex. There was some evidence of a more rapid
      decline in the rate of severe injuries than in minor ones. Further steps need to
      be taken to reduce the number of casualties from road accidents, as road
      accidents represent a major public health problem in Western Australia.

PMID- 1391153
TI  - Identifying hazards and risk opportunity in child farm injury.
AB  - Although children are overrepresented in farm injury, little is known about the
      environmental hazards and risk behaviours associated with injury, or about how to
      identify these factors at a local level. This study addresses the measurement of
      these hazards and hazardous behaviours. The study was conducted in 1990 at
      Gloucester, New South Wales, a small dairy, beef and hobby farm community. After
      some formative research and local consultation, a checklist survey was
      constructed and sent to 120 farm families with school-age children. Families were
      sent the checklist forms again two weeks later to assess test-retest reliability,
      which was found to be acceptable among the 38 per cent who responded on both
      occasions. The findings on the prevalence of environmental hazards and risk
      behaviours from the 84 per cent of respondents were useful to refine the existing
      injury information available from local hospital morbidity figures, which had
      identified injuries related to riding (horses, bicycles and motorcycles) and to
      machinery and drowning as major rural injury issues. In particular the importance
      of bicycle riding and horse-related injury were confirmed. The survey importantly
      identified some previously undetected issues, most notably the danger to
      children's hearing. The prevalence data were used to identify targets for the
      development of local health promotion initiatives, leading the local farm safety
      action group to select horses, helmets and hearing as issues for preventive
      action. Findings from the method indicated the importance of local information,
      involving farmers in constructing the checklist, and feeding back results to the
      community.

PMID- 1391154
TI  - Dogma disputed: potential endemic heterosexual transmission of human
      immunodeficiency virus in Australia.
AB  - The concept of tertiary sexual transmission of human immunodeficiency virus (HIV)
      has been central to government efforts to communicate notions of risk to
      heterosexuals in Australia. Data on heterosexually transmitted acquired immune
      deficiency syndrome (AIDS) and HIV for Australia are reviewed with emphasis given
      to the probability of misclassification bias in the heterosexually acquired and
      'other/undetermined' categories. Tertiary cases are almost certainly rare in
      Australia, with little evidence of any increase in their incidence since the
      first cases were recorded. Three factors (low probability of exposure, the
      infectivity of HIV and a comparatively low rate of sexual partner change) make it
      improbable that Australian heterosexuals with no risk factors will experience
      endemic HIV infection, with a caveat to this conclusion lying in the potential of
      Australian sex tourism to Southeast Asia for introducing HIV into the Australian
      heterosexual population. Four hegemonic factors which have acted to suppress any
      serious debate of the notion that HIV in Australia is unlikely to become endemic
      among heterosexuals are discussed: the political 'democratization' of risk
      inspired by concerns that gay men should not be further vilified as a victim
      group; the preventive imperative; a reluctance among health educators to question
      the very foundations of the message they are employed to deliver; and a
      reluctance to curtail 'Trojan horse' benefits to sexually transmissible disease
      prevention engendered by HIV education promoting safe sex messages.

PMID- 1391155
TI  - Discourse analysis: a new methodology for understanding the ideologies of health
      and illness.
AB  - Discourse analysis is an interdisciplinary field of inquiry which has been little
      employed by public health practitioners. The methodology involves a focus upon
      the sociocultural and political context in which text and talk occur. Discourse
      analysis is, above all, concerned with a critical analysis of the use of language
      and the reproduction of dominant ideologies (belief systems) in discourse
      (defined here as a group of ideas or patterned way of thinking which can both be
      identified in textual and verbal communications and located in wider social
      structures). Discourse analysis adds a linguistic approach to an understanding of
      the relationship between language and ideology, exploring the way in which
      theories of reality and relations of power are encoded in such aspects as the
      syntax, style and rhetorical devices used in texts. This paper argues that
      discourse analysis is pertinent to the concerns of public health, for it has the
      potential to lay bare the ideological dimension of such phenomena as lay health
      beliefs, the doctor-patient relationship, and the dissemination of health
      information in the entertainment mass media. This dimension is often neglected by
      public health research. The method of discourse analysis is explained, and
      examples of its use in the area of public health given.

PMID- 1391156
TI  - Cultural identification in aboriginal and Torres Strait Islander AIDS education.
AB  - The emergence of the disease AIDS in the early 1980s has resulted in a unique
      response. Medical, sociocultural, political, sexual, moral and racial issues have
      all been raised. This paper examines the way in which participation of Aboriginal
      and Torres Strait Islander people has resulted in the culturally appropriate and
      distinctive approaches evident in health education materials produced in
      Aboriginal and Torres Strait Islander communities. Specific cultural issues
      relevant to AIDS education are considered, including the use of visual and
      narrative communication for AIDS education; the significance of the specific
      concepts related to communication on sexual issues; perceptions of AIDS as alien
      and genocidal; the use of the Dreaming in AIDS educational resources; and
      implications for AIDS education.

PMID- 1391157
TI  - The national cot death prevention program in New Zealand.
AB  - A case-control study examining the risk factors for sudden infant death syndrome
      (SIDS) in New Zealand identified three risk factors that are potentially amenable
      to modification: prone sleeping position of the infant, maternal smoking and lack
      of breastfeeding. In total these three risk factors may account for 79 per cent
      of deaths from SIDS in New Zealand. We describe the planning and implementation
      of the cot death prevention program, which has involved a wide range of groups
      and different strategies. The outcome of the prevention program is being
      evaluated.

PMID- 1391158
TI  - Evaluation of a heart disease survey and education program for general
      practitioners.
AB  - In 1989 we mailed a questionnaire to all 461 general practitioners (GPs)
      identified as currently practising in the Eastern Metropolitan Health Region of
      Sydney. This was the first phase of a program to assess, amplify and reassess
      GPs' knowledge of the risk factors for heart disease and measure their attitudes
      and beliefs about their role in the prevention of cardiovascular disease. The
      second phase was an education program designed to meet the needs identified by
      the first questionnaire. Phase three was a postintervention questionnaire. Fifty
      six per cent (260/461) responded to the first questionnaire. This follow-up group
      were mailed the second questionnaire, to which 52 per cent (135/260) responded.
      Thirty per cent of the original sample (139/461) attended the education program
      and 30 per cent (79/260) of the follow-up group did so. At baseline, the
      respondents' level of risk factor knowledge was good, but after the education
      program there was still a large gap between what they said they knew and the
      amount of advice they said they would give to patients. The only significant
      increase in the amount of advice after the intervention was to 'control blood
      pressure'. This applied whether the GP had participated in the intervention or
      not. When GPs were asked how often in the last month they had actually given
      advice to reduce cardiovascular disease risk, program attenders reported offering
      it more frequently than nonattenders. We also attempted to determine whether any
      particular demographic characteristics could predict respondents to the
      questionnaires and/or the educational program.

PMID- 1391159
TI  - Food in low-income families.
AB  - This descriptive study used both quantitative and qualitative research methods to
      examine the food and nutrient intake, food purchasing patterns and budgeting
      strategies of 29 sole-parent low-income families with dependent children living
      in Corio Shire, Victoria, in 1989-90. Expenditure on food and nonalcoholic
      beverages when compared with the average for all Australian households showed
      that the study families allocated a greater proportion, but similar amounts of
      money to cereals, dairy products, fruit and vegetables and miscellaneous foods,
      and less to meat, nonalcoholic beverages and food eaten away from home. Despite
      large differences in the amount of money spent in the first and second weeks of a
      social security payment period, the nutrient density of the parents' diets was
      maintained at a similar level in both weeks. The only exception was vitamin C,
      for which the median intake was significantly lower in the second week,
      consistent with reduced purchases of fruit and vegetables in the same period. In
      interviews with 13 of the parents a variety of purchasing and budgeting
      strategies were described, indicating common concerns with making the most of
      their limited resources. The data from this study support the notion that low
      income families give priority to food purchases above other expenses such as
      recreation. They also support the view that low-income families are concerned
      about health and nutrition and manage to consume nutritionally sound diets under
      difficult circumstances. Nutrition education programs could support them in this
      endeavour.

PMID- 1391160
TI  - Preventive health behaviours among parents of infants aged four months.
AB  - Six preventive health behaviours have been frequently identified as having the
      potential to reduce mortality and morbidity during infancy: breast-feeding until
      the age of six months; no solid food until after four months of age; immunisation
      against whooping cough, diphtheria, poliomyelitis and tetanus; the use of a baby
      capsule to restrain the infant when travelling in a motor vehicle; regular
      attendance at a health care provider for preventive health checks; and no
      maternal smoking. This study surveyed 191 primiparous women four months after the
      birth of their babies to explore the proportion of parents who perform the
      recommended preventive health behaviours and the association among the
      behaviours. Thirty-nine per cent of the women reported that they were no longer
      breast-feeding by the time their infant was four months old; 35 per cent had
      introduced solids before 16 weeks of age; 35 per cent did not always use a baby
      capsule when travelling with their baby in their car, 25 per cent did not
      regularly attend the early childhood health centres and 22 per cent smoked. Forty
      eight per cent of the sample were performing four or fewer of the six preventive
      health behaviours and 21 per cent were performing three or fewer. The
      relationship between performing each preventive health behaviour and a range of
      demographic variables was investigated. A logistic regression indicated that
      performing three or fewer of the health behaviours was associated with lower
      levels of education, having public health insurance and being born in a country
      other than Australia.

PMID- 1391161
TI  - Coffee shops and clinics: the give and take of doing HIV/AIDS research with
      injecting drug users.
AB  - We discuss recruiting and interviewing injecting drug users and using research as
      health promotion in the context of collecting information related to human
      immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) from a
      convenience sample of 200 injecting drug users, half in treatment and half not,
      in 1989 and 1990 in Perth, Western Australia. A variety of recruiting methods
      were used including advertising, referral by agency staff, 'snowballing' and
      approaches to personal contacts and others known to inject by the interviewer.
      Snowballing and personal contacts were the most successful means of recruiting
      those not in treatment, while advertising was comparatively unsuccessful with
      this group because of the importance of establishing the credibility of the study
      and the interviewer among injecting drug users before they will volunteer to be
      involved. The promotion of behavioural risk reduction among respondents during
      the interview is detailed. We argue that the traditionally rigid separation
      between research and intervention is inappropriate in the HIV/AIDS context. When
      lives are potentially at stake, any contact with injecting drug users, especially
      those not in treatment (where may receive HIV/AIDS education), must be used as an
      HIV/AIDS prevention opportunity, and the interview is an ideal opportunity. The
      employment of research as community intervention is also discussed.

PMID- 1391162
TI  - Self-help smoking cessation materials.
AB  - Smoking-cessation campaigns and services use printed self-help materials as a
      major medium for assisting smokers to quit. Such materials are associated with
      abstinence rates of up to 20% at 12-month follow-ups. Adherence to the specific
      content of self-instructional programs can be poor, but higher levels of reported
      adherence may be associated with a greater likelihood of cessation. Personalized
      cessation materials do not enhance cessation rates, but social support and
      minimal levels of personal contact do. Research is needed to identify which
      specific components of these programs are effective, how adherence may be
      promoted and how materials may be used in conjunction with other interventions-
      particularly cost-effective forms of counselling and social support.

PMID- 1391163
TI  - Sunglasses and clothing--an unhealthy correlation?
AB  - Increasing awareness of health effects of solar ultraviolet radiation has focused
      attention on protection measures, including sunglasses. Sunglasses, or fashion
      glasses with tinted lenses, may be associated with some risks, and quality is not
      evident from casual inspection. This study investigates one possible 'hazard' of
      sunglasses--that they may induce behavioural changes which reduce the wearer's
      tendency to use adequate sun protection for the rest of the body. Findings
      consistent with such a proposition were shown in a photographic survey of 373
      people in the summer of 1991 in Perth, Western Australia. This revealed
      maladaptive associations between the wearing of sunglasses and a high degree of
      leg or arm exposure as recorded by length of sleeves or trouser legs. This was
      significant for the arms and the legs in males (P less than 0.05), but approached
      significance only for the arms in females (P less than 0.10). There was no
      significant association between degrees of arm and leg exposure in either sex.
      The health implications of these maladaptive behaviours, and some advantages and
      disadvantages of the survey technique, are discussed. The results suggest that
      promotion of sun-protective behaviour should encourage the use of both sunglasses
      and protective clothing, as subjects' behaviours with respect to these do not
      appear to be correlated in a rational manner. If public awareness of links
      between skin cancer and eye disease could be increased, promotion of sunglasses
      might lead to a reduction in the incidence of skin cancers in general, not just
      those in the periorbital area.

PMID- 1391164
TI  - The family v. the family court: sterilisation issues.
AB  - Parents as guardians of minor children have the right and duty to give and
      withhold consent to medical treatment when the treatment is neither routine nor
      urgent. Parental authority, however, is not absolute and dwindles as the child
      gradually matures. In general, teenagers can give consent to medical treatment if
      they understand the nature and consequences of the proposed treatment. The
      diminution of parental authority is based on the premise that the child will
      eventually become autonomous. In cases where a sterilisation or hysterectomy
      procedure is being considered for a severely intellectually disabled teenager the
      question of consent is most contentious. Should this power belong to parents or
      the state? This paper examines some recent Family Court cases concerning this
      issue and also addresses questions about human rights, medical autonomy and the
      role of the Family Court. Finally, a proposal for an alternative means of
      decision-making in these cases is briefly outlined.

PMID- 1391165
TI  - Monitoring heterosexually transmitted HIV infection in Australia.

PMID- 1391167
TI  - Measles immunisation.

PMID- 1391166
TI  - Low birthweight and socioeconomic status.

PMID- 1391168
TI  - Otitis externa induced with Malassezia pachydermatis in dogs and the efficacy of
      pimaricin.
AB  - Eight beagles were experimentally inoculated intraotally with Malassezia
      pachydermatis to induce acute otitis externa. Three or 4 days after the
      inoculation, the animals showed the symptoms of otitis externa. All ear canals
      were erythematous and the dogs were shaking their heads. A large number of M.
      pachydermatis was noticed in exudate taken from every ear canal. Clinical signs
      of otitis externa were reduced after treatment with 0.1 ml (per canal) of 1%
      pimaricin suspension twice a day for 3 days. The amount of exudate decreased
      gradually and 12 of the 16 ear swabs examined, thereafter, were found to be
      negative for M. pachydermatis within 10 days. No side effects were observed in
      all the treated cases. These results suggested that M. pachydermatis could induce
      the canine otitis externa, and that pimaricin is effective agent for M.
      pachydermatis infection in ear canals.

PMID- 1391169
TI  - A balanced anesthesia with a combination of xylazine, ketamine and butorphanol
      and its antagonism by yohimbine in pigs.
AB  - The effects of intramuscular injections of xylazine (2 mg/kg)-ketamine (15 mg/kg)
      [X-K15], and xylazine (2 mg/kg)-ketamine (5 mg/kg)-butorphanol (0.22 mg/kg) [X-K5
      B] were compared in atropinized (0.05 mg/kg) miniature pigs (pigs). Both
      combinations induced the anesthesia for more than 1 hr, however X-K5-B induced
      the more potent and well balanced anesthesia as compared with X-K15, although the
      amount of ketamine was reduced to one third. The duration of loss of pedal
      reflex, an indicator of surgical anesthesia, in X-K5-B (62 +/- 13 min) was
      significantly (P less than 0.05) longer than in X-K15 (28 +/- 19 min). In
      addition, X-K5-B was accompanied by loss of laryngeal reflex in all pigs.
      Recovery from anesthesia in X-K5-B was much smoother than in X-K15, and the
      administration of yohimbine (0.05 mg/kg) could rapidly and smoothly reverse the
      anesthesia induced by X-K5-B, although it was accompanied by a transient fall in
      blood pressure and tachycardia. The combination of xylazine, ketamine and
      butorphanol appears to be a relatively safe and widely available anesthesia for
      the period of one hour in pigs.

PMID- 1391170
TI  - Evaluation of plasma erythropoietin levels in normal adult dogs by in vivo
      bioassay using concentrated plasma.
AB  - Measurement of plasma erythropoietin level in normal dogs by in vivo bioassay has
      been considered to be impossible so far. In the present study, we successfully
      determined it by using concentrated plasma 60 times which allowed the lower limit
      to 2.7 mU/ml. This normal plasma erythropoietin level was the first to be
      determined as an in vivo bioactivity and was 9.14 +/- 7.81 mU/ml in 75 normal
      adult dogs. This value was sufficiently reliable in terms of accuracy of
      determination and considered to be meaningful as the low level in vivo
      bioactivity that hasn't been known to date. Furthermore, erythropoietin levels in
      normal plasma were within a certain lower range and showed neither difference in
      plasma erythropoietin level between males and females or among breeds nor
      correlation between erythropoietin and hemoglobin level.

PMID- 1391171
TI  - Role of adherent spleen cells in the induction of cytotoxic activity by
      Toxoplasma lysate antigen.
AB  - In order to identify mechanisms responsible for the anti-tumor effects of
      Toxoplasma lysate antigen (TLA), we used an in vitro 51Cr release assay to study
      the functional properties of plastic-adherent cells during induction of splenic
      cytotoxic activity by TLA. Cytotoxic activity of non-adherent cells was measured
      in all experiments after a 6 days incubation. Induction of cytotoxic non-adherent
      cells by TLA required the presence of plastic-adherent spleen cells. In contrast,
      rhIL-2 alone was able to induce transformation of cytotoxic non-adherent cells
      from non-adherent spleen cells. Contact between adherent and non-adherent spleen
      cells was necessary for successful induction of cytotoxic non-adherent cells by
      TLA. Treatment of spleen cells with anti-macrophage serum prevented induction of
      cytotoxic activity by TLA. Biologically active IL-2 was not detected in culture
      supernatants of spleen cells exposed to TLA. These findings suggest that contact
      between TLA-sensitized non-adherent cells and macrophages is necessary for
      induction of cytotoxic cells in the presence of TLA. This contact, however, is
      not necessary for generation of IL-2-induced killer cells.

PMID- 1391172
TI  - Effect of hyperlipidemia on cardiovascular responses to adrenergic stimulation in
      piglets.
AB  - This study was designed to assess the effect of hyperlipidemia on cardiovascular
      responses to adrenergic stimulation in a porcine model. Four-week-old piglets (n
      = 10) were divided into two groups; one fed a control diet and the other was fed
      an atherogenic diet for 8 weeks. Cardiovascular responses were evaluated to both
      norepinephrine (NE; 0.5 and 2.5 micrograms/kg) and isoproterenol (ISO; 0.1 and
      0.5 microgram/kg) from simultaneous recordings of femoral arterial pressure,
      heart rate, left intraventricular pressure and left intraventricular dP/dt. It
      was found that no significant difference in the baseline values of cardiovascular
      function was observed between the control and hyperlipidemic groups. However, in
      the hyperlipidemic group as compared with the control group: 1) arterial blood
      pressure responses to NE were significantly increased (P less than 0.05), 2)
      cardiac contractile responses to NE and ISO were significantly potentiated (P
      less than 0.05), and 3) reflex bradycardia in response to increasing arterial
      blood pressure did not occur. These findings indicate that hyperlipidemia can
      potentiate the cardiovascular responses to adrenergic stimulation, whereas reflex
      cardiovascular regulation is somewhat altered by hyperlipidemia. Conceivably,
      these observations may have relevance to the possible role of the mechanism of
      the interaction of hyperlipidemia and hypertension in atherogenesis.

PMID- 1391173
TI  - Sedative effects of medetomidine in pigs.
AB  - Sedative effects of medetomidine, a potent selective and specific alpha 2
      adrenoceptor agonist, were evaluated in pigs using 5 different doses (30, 50, 80,
      100 and 150 micrograms/kg of body weight) and compared with those of xylazine (2
      mg/kg). Atropine (25 micrograms/kg) was mixed with both drugs to prevent severe
      bradycardia. All drugs were administered intramuscularly. Medetomidine at a
      dosage of 30 micrograms/kg produced more potent sedation than xylazine. The depth
      of sedation induced by medetomidine was dose dependent within the range from 30
      to 80 micrograms/kg. At 100 or 150 micrograms/kg, the depth of sedation was
      mostly the similar level to that at 80 micrograms/kg but the duration was
      prolonged. The degree of muscle relaxation produced by medetomidine also seemed
      to be dose dependent from 30 to 80 micrograms/kg and was stronger than that
      produced by xylazine. An increase in the duration of muscle relaxation was dose
      dependent up to 150 micrograms/kg. No analgesic effect was produced by xylazine,
      however moderate analgesia was obtained by medetomidine. There were no marked
      changes in heart rate and respiratory rate during the observation period in pigs
      of any groups, however mild hypothermia after the administration of both drugs
      was observed. From these results, medetomidine has a significant and dose
      dependent sedative effects which are much more potent than that of xylazine, and
      a combination of 80 micrograms/kg of medetomidine and 25 micrograms/kg of
      atropine is suitable for sedation with lateral recumbency and moderate muscle
      relaxation without notable side effects in pigs.

PMID- 1391174
TI  - Serological survey of Rhodococcus equi infection in horses in Hokkaido.
AB  - Serological survey of Rhodococcus equi infection in horses in Hokkaido was
      performed using ELISA. Of 2,879 horse sera, 318 (11.0%) gave antibody-positive
      (OD greater than or equal to 0.3) reactions. The antibody-positive rate of female
      was significantly higher (p less than 0.01) than that of male, and no statistical
      difference between Anglo-Arab and thoroughbred was detected in the antibody
      positive rate. The maximum antibody-positive rate (27.1%) was shown at 14 years
      of age. The antibody-positive rates on the 160 farms were found to vary widely
      from 0 to 78.9%. A significant difference (p less than 0.01) in the antibody
      positive rate was detected among horse farms. It was elucidated that 100 (62.5%)
      out of 160 horse farms had an antibody-positive horse. These results indicate
      that R. equi was widespread on horse farms, and the level of environmental
      contamination with R. equi differed among horse farms.

PMID- 1391175
TI  - Effect of soft x-ray irradiation on immunological functions in mice.
AB  - Effect of soft x-ray irradiation on immunological functions in mice was
      investigated. Soft x-ray irradiation with 100R or more induced a significant
      reduction in the number of plaque-forming cells (PFC). The reduction in the
      number of PFC depended on the irradiation doses. Irradiation with 600R or more
      showed a significant reduction in the delayed reaction of footpad swelling.
      However, soft x-ray irradiation with doses ranging from 100R to 1000R did not
      exert significant influence on the K values of carbon clearance test. Irradiation
      with 100R or more of soft x-ray showed a remarkable reduction of response to
      concanavalinA (ConA) or lipopolysaccharide (LPS) in spleen cells, and the
      response to ConA was lower than that to LPS. These results suggest that in the
      soft x-ray-irradiated mice, antibody-producing ability, delayed type
      hypersensitivity reaction and mitogenic activity are sensitive to soft x-ray
      irradiation and furthermore, T cell is more sensitive than B cell, but phagocytic
      activity of reticulo-endothelial system (RES) is resistant to soft x-ray
      irradiation.

PMID- 1391176
TI  - Immunohistochemical studies on canine cerebral amyloid angiopathy and senile
      plaques.
AB  - Amyloid protein was isolated from the cerebral meninges of 4 aged dogs with
      cerebral amyloid angiopathy. By immunoblot analysis, antiserum against synthetic
      oligo-peptide consisting of 1-28 amino acid of amyloid beta protein recognized
      prominent wide band ranging from 14 to 18 kilodalton (kd). When amyloid samples
      were solubilized by formic acid, the antiserum recognized lower molecular weight
      band ranging from 3 to 4 kd. Immunohistochemical studies on cerebral amyloid
      angiopathy and senile plaques were performed in 17 aged dogs. Anti-amyloid beta
      protein serum labeled amyloid deposits in cerebral vessel walls and senile
      plaques. Compact deposits of beta protein were detected in primitive or classical
      plaques. After using formic acid pretreatment, diffuse deposits of beta protein
      in the neuropil representing diffuse plaques were detectable. Classical and
      primitive plaques reacted with antiserum against glial fibrillary acidic protein,
      while not with antisera against alpha 1-antichymotrypsin, IgG and IgM. Amyloid
      deposits in the intestines of aged dogs examined, did not react with anti-amyloid
      beta protein serum.

PMID- 1391178
TI  - Biological and biophysical characteristics of phages isolated from Clostridium
      botulinum type C and D strains, and physicochemical properties of the phage DNAs.
AB  - Toxin-converting phages CE beta and d-16 phi and non-converting phages CE gamma
      and d-1', isolated from toxigenic strains C-468 and D-CB16 of Clostridium
      botulinum types C and D, respectively, were characterized biologically and
      biophysically. DNAs isolated from these four phages were studied
      physicochemically. Phages CE beta, d-16 phi, CE gamma and d-1' were adsorbed to
      their susceptible cells at the constant rates of 1.1 x 10(-8), 3.3 x 10(-8), 1.4
      x 10(-8) and 1.4 x 10(-8) ml/min, and grew after latent periods of 35, 45, 35 and
      35 min at the burst sizes of 38, 85, 35 and 35, respectively. Converting phages
      were more susceptible than non-converting phages to physical and chemical
      treatments such as temperature, pH, time, UV-irradiation and organic solvents.
      GC% of phage DNAs were determined by melting temperature, buoyant density and
      HPLC analysis to be 26, 26, 29 and 29% for CE beta, d-16 phi, CE gamma and d-1'
      phage DNAs, respectively. The restriction digestion profiles of phage DNAs with
      seven endonucleases were compared by agarose gel electrophoresis, revealing that
      the two converting phage DNAs were similar in regard to five enzyme digestion
      profiles, but different in the other two enzymatic profiles. Non-converting phage
      DNAs produced the same restriction digestion profiles with all seven
      endonucleases. The molecular sizes determined from the size of restriction enzyme
      digestion fragments were about 110 kb for converting phage CE beta and d-16 phi
      DNAs and 65 kb for non-converting phage CE gamma and d-1' DNAs. Dot blot
      hybridization experiments revealed that DNA homology between the converting
      phages CE beta and d-16 phi was 50-75%, while that between non-converting phages
      CE gamma and d-1' was about 100%. Converting phage and non-converting phage DNAs
      did not hybridize at all.

PMID- 1391177
TI  - Effects of atherosclerosis on mean and daily variation of arterial pressure in
      conscious WHHL rabbits.
AB  - Effects of atherosclerosis on the mean value and daily variation of arterial
      pressure were studied in 12 Watanabe-heritable hyperlipidemic (WHHL) rabbits aged
      12 to 35 months and 25 normal Japanese white rabbits aged 6 to 30 months. A
      pressure catheter was inserted through the left subclavian artery under
      pentobarbital anesthesia. A few days after the catheterization, the mean arterial
      pressure (MAP) of the rabbits, which were active and in a good state of appetite,
      was recorded by an analogue-to-digital converter every second for about 6 hrs and
      stored in a computer. The mean (M) and standard deviation (SD) in the WHHL
      rabbit, calculated from each successive MAP record, ranged widely from 85.8 to
      131.4 mmHg and 5.6 to 12.6 mmHg, respectively. There was no significant
      correlation between M and SD in the WHHL rabbit. M and variance (V) of MAP in the
      WHHL rabbit were significantly higher than those in the normal rabbit. M did not
      show any significant change with increasing ages, whereas SD increased
      significantly with aging in the WHHL rabbit. Concentrations of serum total
      cholesterol and triglyceride in the WHHL rabbit were 475 and 328 mg/dl, which
      were about nine and seven times as high as those in the normal rabbit,
      respectively. Macroscopic and histopathological examinations of the aorta
      revealed development and spread of sclerotic lesions with aging in the WHHL
      rabbit. We can conclude that development of atherosclerosis with aging in the
      WHHL rabbit causes malfunction of the baroreceptors, which contributes to
      hypertension and lability of arterial pressure.

PMID- 1391180
TI  - Isolation and identification of intestinal bacteria from Japanese tree frog (Hlya
      japonica) with the special reference to anaerobic bacteria.
AB  - The bacteria in the large intestines of eight Japanese tree frogs (Hlya japonica)
      were enumerated by using an anaerobic culture system. The microorganisms at
      approximately 3.1 x 10(9) bacteria per g (wet weight) of intestinal contents were
      present in the intestine of all the frogs tested. No difference of the total
      bacteria in the frog intestine was observed between two different incubation
      temperatures (room temperature and 37 degrees C). Eleven genera and 16 species
      were isolated from the frog intestine. In most frogs, Bacteroides (B.) caccae and
      B. vulgatus were detected as the predominant organisms. Escherichia coli was also
      present in greater numbers in the intestine. Other bacteria isolated at high
      dilutions were strict anaerobes, including Fusobacterium and Clostridium.
      Enterococcus faecalis was frequently isolated from the frog intestine. However,
      four genera of Bifidobacterium, Eubacterium, Peptostreptococcus, and
      Lactobacillus were not isolated from the frog intestine.

PMID- 1391179
TI  - Pathological studies on local tissue reactions in guinea pigs and rats caused by
      four different adjuvants.
AB  - We investigated pathological changes at the injection site in guinea pigs and
      rats for 16 weeks following a single intramuscular injection of one of the
      following oil adjuvant emulsions; oil adjuvant ISA-70, Freund's incomplete
      adjuvant, Freund's complete adjuvant, and aluminium phosphate gel. In the animals
      injected with ISA-70 emulsion prepared by manual shaking, grossly, there was
      partial thickening of subcutaneous tissue, discoloration of inter-muscular
      connective tissue, and swelling of the inguinal lymph nodes at 2 and 4 weeks post
      injection (PI). Histopathologically, ISA-70 injected sites revealed acute
      inflammatory changes at 72 hrs PI, and peak reactions consisting of macrophage
      accumulation around oil cysts and fibrosis were observed at 4 weeks PI. These
      changes were less severe and of shorter duration than those in the other three
      adjuvants. Guinea pigs and rats injected with materials containing inactivated
      Newcastle disease virus (NDV) antigen similarly showed an infiltration of plasma
      cells and lymphocytes in addition to the changes described above. ISA-70
      containing NDV antigen induced similar hemagglutination-inhibition titer to that
      induced by Freund's incomplete adjuvant.

PMID- 1391181
TI  - Impact of the advances in age on the gastrointestinal microflora of beagle dogs.
AB  - The gastrointestinal microflora of male beagle dogs in two different age groups;
      I) less than month 12 of age, and II) more than year 11 of age, was compared. No
      detectable difference occurred on the microflora of stomach, duodenum, jejunum,
      and ileum in both dogs. Large bowel (cecum, colon and rectum) microflora in both
      dogs yielded the different microbial populations. In all regions of large bowel,
      the levels of bacteroides, eubacteria, peptostreptococci, bifidobacteria,
      lactobacilli, and staphylococci in the elderly dogs were lower than those in the
      younger animals, whereas the numbers of Clostridium perfringens and streptococci
      in the elderly animals were higher than those in the youngers. The high incidence
      of lecithinase-negative clostridia was observed with advances in age, but not
      that of spiral shaped rods. The result of this study shows that the advances in
      age of beagle dogs yield some changes in the microbial population of large bowel
      in the animals.

PMID- 1391182
TI  - Characteristics of ventricular activation and recovery patterns in the rat.
AB  - Bipolar or unipolar epicardial and intraseptum electrograms were recorded from
      the in situ rat hearts with spontaneous sinus rhythm or myocardial electrical
      stimulation of 400 bpm in order to investigate the sequence and duration of
      cardiac activation in the rat. The ventricular epicardial isochronous maps in the
      rat showed the activation sequence comparable to those in humans and dogs,
      although the activation time (6 to 13 msec) of epicardium was approximately one
      third of those of such species. The delay of activation between septum and
      ventricular surface in the rat was 5 to 8 msec, which was also shorter as
      compared with those in humans and dogs. However, the conduction velocity of the
      ventricular epicardium in the rat was approximately 40 cm/sec, mostly equal to
      that of humans. These findings might be accounted for by the possible presence of
      the bundle branch-purkinje system, at least functionally, similar to humans. The
      local QT interval in the septum were relatively longer (69 to 123 msec), compared
      with that of the ventricular surface (50 to 98 msec), and such durations of
      ventricular epicardium and septum were considerably less than those of dogs and
      humans. These results are consistent with the configuration of QRS-T on the limb
      lead ECG.

PMID- 1391183
TI  - Isolation of secretory IgA from feline bile and bile IgA levels in growing cats.
AB  - Secretory IgA was isolated from feline bile, using ammonium sulphate
      precipitation, gel-filtration chromatography and affinity chromatography. It
      formed a precipitating line between anti-cat whole serum or anti-cat bile serum
      by immunoelectrophoresis and double diffusion. It consisted of three subunits
      that molecular weight were 80 kd, 62 kd and 27 kd by SDS-PAGE analysis. The 80 kd
      protein was equivalent to secretory component of human and other animals.
      Immunoglobulin levels were observed on bile collected continuously by gallbladder
      cannulation in growing cats. Although immunoglobulins were not detected in bile
      of feline fetus, after birth its levels increased gradually. Biliary IgA levels
      reached the adult levels earlier than that of their serum.

PMID- 1391184
TI  - Effects of estrous cycle, estrogen and progesterone administration on the
      antidromic and orthodromic reaction threshold of medial preoptic neurons in the
      rat hypothalamus.
AB  - In the present study, attempts were made to evaluate the effects of the estrous
      cycle and the administration of estradiol (Ovx-E) or progesterone (Ovx-P) after
      ovariectomy on the threshold of antidromic (AD) and orthodromic (OD) responses of
      neurons in the medial preoptic area (POA) induced by electrical stimulation of
      the median eminence-arcuate nucleus (ARC) of the hypothalamus. Single units were
      evaluated with extracellular recording. The threshold of AD and OD response in
      POA neurons declined during estrus and proestrus of the estrous cycle and in the
      Ovx-E group, but increased in the Ovx-P group and during diestrus. The number of
      neurons with the inhibitory OD response increased during proestrus and in the Ovx
      E group, but decreased during diestrus. The neurons with the excitatory OD
      response increased in the Ovx-P group and during diestrus, and decreased during
      proestrus. The threshold of the inhibitory and excitatory OD response decreased
      during proestrus, estrus and in the Ovx-E group, but increased in the Ovx-P
      group. It is apparent from these studies that estrogen appears to activate the
      neurons of the POA receiving inhibitory synaptic input via the axonal collateral
      branches of the ARC neurons, and that progesterone seems to activate the neurons
      of the POA receiving excitatory synaptic input.

PMID- 1391185
TI  - Analysis of swinepox virus antigens using monoclonal antibodies.
AB  - Seventeen monoclonal antibodies (MAbs) against swinepox virus (SPV) were produced
      and characterized. These MAbs were classified into eight groups (A through H) on
      the basis of the molecular weight of the polypeptides which they recognized and
      the staining patterns of antigens in SPV-infected cells by the indirect
      immunofluorescent (IF) technique. The MAbs belonging to groups A, B, C and G
      recognized late antigens in cytoplasmic inclusion bodies with molecular weights
      of 97 kD, 65 kD, 48 kD and 15 kD, respectively. The MAbs belonging to groups D
      and H respectively recognized 35 kD and 12 kD late antigens, which first appeared
      in cytoplasmic inclusion bodies and spread to the cytoplasms and surface
      membranes of the infected cells. The MAb of group F recognized an 18 kD late
      antigen with granular distribution in the cytoplasm. The MAbs of group E
      recognized a 32 kD early antigen. Although all the MAbs belonging to the six
      groups (A, D through H) were specific for SPV, some of those belonging to groups
      B and C showed cross-reactivity with members of the other genera of poxviridae.
      An MAb in group B, SP14, cross-reacted with orf and rabbit fibroma viruses. Two
      MAbs in group C, SP24 and SP32, cross-reacted with vaccinia, cowpox, ectromelia,
      and rabbit fibroma viruses. These findings indicate that at least two SPV
      antigens contain cross-reactive epitopes with different genera of poxviridae.

PMID- 1391186
TI  - Relationship between pulmonary arterial pressure and lesions in the pulmonary
      arteries and parenchyma, and cardiac valves in canine dirofilariasis.
AB  - The relationship between pulmonary hypertension and lesions was examined in 41
      dogs infested naturally with heartworms, which consisted of 28 cases with
      pulmonary heartworm disease and 13 cases with caval syndrome. Pulmonary arterial
      pressure (PAP) was measured before and 1 or 7 days after heartworm removal with a
      flexible alligator forceps. In these dogs, lesions were examined after the last
      measurement of PAP. The mean PAP was 28.2 +/- 16.0 mmHg (10.9 to 81.4 mmHg in
      range) at post-removal phase. Pulmonary arterial intimal lesions, pulmonary
      thromboemboli, pneumonic lesions, tricuspid valvular lesions and mitral valvular
      lesions were macroscopically recognized in 95, 59, 39, 54 and 56% of cases,
      respectively. These lesions were classified by severity and the relationship with
      PAP was examined by the multiple correlation analysis. The multiple coefficient
      correlation was found the highest between PAP and thromboemboli, followed by
      mitral valvular lesion, tricuspid valvular lesion, and pneumonic lesion. There
      was no significant correlation between PAP and intimal lesions. The coefficient
      of determination showed the highest value in thromboemboli when one variable was
      used, and increased only very slightly when a variable of thromboemboli was added
      to those of other lesions. The cases with high PAP had fresh thromboemboli in
      large pulmonary arteries. From these evidences, it was concluded that
      thromboemboli following natural death of heartworm was the most important factor
      causing an increase in PAP and developing clinical signs in canine heartworm
      disease.

PMID- 1391187
TI  - Cardiopulmonary function in dogs with serious chronic heartworm disease.
AB  - Cardiopulmonary function was examined in 18 dogs with serious chronic heartworm
      disease showing ascites, subcutaneous edema, prostration, weakness, jaundice and
      so on. After surgical heartworm removal from the pulmonary arteries, 10 dogs
      recovered (surviving group), and 8 dogs died or were euthanatized because of poor
      prognosis (nonsurviving group). The number of live heartworms residing in the
      pulmonary arteries of the surviving group tended to be larger than that in the
      nonsurviving group. At necropsy, severe pulmonary arterial lesions such as
      thromboembolism including dead heartworms, proliferative and villous lesions and
      intimal hyperplasia were noticed in all dogs examined, and tended to be severer
      in the nonsurviving group. Heartworm-coiling around the tricuspid valve chord was
      found in 1 dog of the surviving group and 4 dogs of the nonsurviving group.
      Before heartworm removal, there was no significant difference in the mean
      pulmonary arterial pressure (MPAP) between the surviving and nonsurviving group.
      Right atrial pressure (v-wave) was higher, and the cardiac index (CI) was lower
      in the nonsurviving group. Arterial oxygen tension was lower in the surviving
      group than in the heartworm-free group, and it was lower in the nonsurviving
      group than in the surviving group. Carbon dioxide tension was lower in the
      surviving group than in the heartworm-free group. Bicarbonate concentration (HCO3
      ) was lower both in the surviving and nonsurviving groups than in the heartworm
      free group. One week after heartworm removal, MPAP decreased (P less than 0.05),
      and CI and HCO3- tended to increase in the surviving group.

PMID- 1391188
TI  - Effect of antibiotics treatment of in vitro fertilized bovine embryos to remove
      adhering bacteria.

PMID- 1391189
TI  - Central nervous system lesions due to Escherichia coli infection in neonatal
      calves.

PMID- 1391190
TI  - Three cases of feline sclerosing lymphocytic cholangitis.

PMID- 1391191
TI  - Partial characterization of the hemolysin produced by Clostridium chauvoei.

PMID- 1391192
TI  - Mode of inheritance of sperm retention cysts in the efferent duct of TE inbred
      rats.

PMID- 1391193
TI  - Mastocytoma in a Fischer 344 rat.

PMID- 1391194
TI  - Glycated hemoglobin fractions in normal and diabetic cats measured by high
      performance liquid chromatography.

PMID- 1391195
TI  - Fecal egg counts in swine experimentally infected with Strongyloides ransomi.

PMID- 1391196
TI  - Influence of a newly synthesized peptide, obiopeptide-1, as a biological response
      modifier (BRM), upon the lysosomal enzyme activities and chemotactic responses of
      mouse macrophages.

PMID- 1391197
TI  - A case of lobar emphysema in a dog.

PMID- 1391198
TI  - In vitro fertilization of follicular oocytes from the swamp buffalo (Bubalus
      bubalis) and Kedah-Kelantan cattle (Bos indicus) in Malaysia.

PMID- 1391199
TI  - Mycobacterium bovis infection in a herd of Japanese Shika deer (Cervus nippon).

PMID- 1391200
TI  - Ultrastructure of endoderm in canine blastocysts.

PMID- 1391201
TI  - Malignant schwannoma in the spinal root of a dog.

PMID- 1391202
TI  - [Inhibition of enzymatic activity of alpha-thrombin by low molecular weight
      synthetic inhibitor].
AB  - The effect of the organophosphoric inhibitor, SA-152, on the fibrinogen
      coagulating and TAME-esterase activity of bovine alpha-thrombin was studied. The
      irreversible inhibition constants (k11 = 1.1 x 10(4) M-1.min-1,Ki = 0.7 x 10(-4)
      M, k2 = 0.8 min-1 towards the coagulating activity and kII = 0.7 x 10(4) M-1.min
      1, Ki = 0.3 x 10(-4) M, k2 = 0.2 min-1 towards the esterase activity) were
      determined. The SA-152 inactivated alpha-thrombin was dialyzed and incubated with
      0.5 M and 2.5 M NaCl and 10 mM TAME. There was no reconstitution of activity of
      the SA-152 modified alpha-thrombin after dialysis and treatment with high
      concentrations of NaCl and TAME. Heparin interactions with the anion-binding site
      of the high molecular weight recognition center in the alpha-thrombin molecule
      did not significantly influence the values of the kinetic constants for the
      enzyme inhibition by SA-152. This finding is consistent with the hypothesis on
      the irreversible binding of SA-152 in the active center of the enzyme.

PMID- 1391203
TI  - [Isolation and properties of three forms of phosphorylase and phosphorylase
      kinase from human skeletal muscle].
AB  - Three forms of phosphorylase (I, II and III), two of which (I and II) were active
      in the presence of AMP and one (III) was active without AMP, were isolated from
      human skeletal muscles. The pI values for phosphorylases b(I) and b(II) were
      found to be identical (5.8-5.9). During chromatofocusing a low molecular weight
      protein (M(r) = 20-21 kDa, pI 4.8) was separated from phosphorylase b(II). This
      process was accompanied by an increase of the enzyme specific activity followed
      by its decline. During reconstitution of the complex the activity of
      phosphorylase b(II) returned to the initial level. Upon phosphorylation the
      amount of 32P incorporated into phosphorylase b(II) was 2 times as low as
      compared with rabbit phosphorylase b and human phosphorylase b(I). It may be
      supposed that in the human phosphorylase b(II) molecule one of the two subunits
      undergoes phosphorylation in vivo. This form of the enzyme is characterized by a
      greater affinity for glycogen and a lower sensitivity to allosteric effectors
      (AMP, glucose-6-phosphate, caffeine) compared with phosphorylase b(I). Thus,
      among the three phosphorylase forms obtained in this study, form b(II) is the
      most unusual one, since it is partly phosphorylated by phosphorylase kinase to
      form a complex with a low molecular weight protein which stabilizes its activity.
      A partially purified preparation of phosphorylase kinase was isolated from human
      skeletal muscles. The enzyme activity necessitates Ca2+ (c0.5 = 0.63 microM). At
      pH 6.8 the enzyme is activated by calmodulin (c0.5 = 15 microM). The enzyme
      activity ratio at pH 6.8/8.2 is equal to 0.18.

PMID- 1391204
TI  - [Comparative kinetic studies of the primary specificity of bovine and salmon
      trypsin].
AB  - A comparative kinetic analysis of Pacific salmon and bovine trypsins revealed
      that the former hydrolyzes p-nitroanilide-N,L-benzoyl-D,L-arginine (BApNA) with a
      far greater efficiency in comparison with bovine trypsin due to the decrease in
      Km. The inhibition constants for the BApNA hydrolysis by bovine and salmon
      trypsin with glycine, beta-alanine, L-lysine, L-arginine and benzamidine were
      determined. With an increase in the length of the hydrocarbon chain in the
      inhibitor molecule (i.e., in the order of glycine-beta-alanine-L-lysine) the
      inhibiting effect increased both with salmon and bovine trypsins. The Ki values
      for benzamidine and L-arginine appeared to be by one order of magnitude higher
      with salmon trypsin than with bovine trypsin. L-arginine was a much more
      effective inhibitor compared to L-lysine when both salmon and bovine trypsins
      were used.

PMID- 1391205
TI  - [Substrate specificity of collagenolytic proteases from the hepatopancreas of the
      of the Kamchatka crab].
AB  - The substrate specificity of two isozymes of collagenolytic protease of the crab
      (Paralithodes camtschatica) was studied. It was found that both proteases can
      effectively hydrolyze type I and III collagens, as well as gelatin, the set of
      products yielded by enzymatic hydrolysis being different for isozymes A and C.
      Hydrolysis of some well-known peptides revealed that isozyme A predominantly
      cleaves the peptide bonds containing arginine and lysine residues, whereas
      isozyme C predominantly hydrolyzes bonds containing hydrophobic amino acids. The
      catalytic constants for the hydrolysis of several low molecular weight substrates
      in the presence of P. camtschatica proteases were determined, which allowed to
      attribute isozyme A to trypsin-like, and isozyme C to chymotrypsin-like
      proteinases. The peptide substrates of collagenase, Pz-Pro-Leu-Gly-Pro-D-Arg and
      Z-Gly-Pro-Ala-Gly-Pro-Ala are not hydrolyzed isozymes of crab collagenolytic
      protease.

PMID- 1391206
TI  - [The role of terminal DNA groups in the activation of (ADP-ribose)polymerase].
AB  - Some peculiarities of activation of (ADP-ribose) polymerase by DNA fragments were
      studied. DNA fragments were produced by the digestion of calf thymus DNA by
      micrococcal nuclease and with a subsequent enzymatic modification of their end
      groups by nuclease S1, polynucleotide kinase of phage T4 and alkaline
      phosphatase. The dependence of the activating effect of DNA on the chemical
      structure of its end groups was established. It was shown that the terminal
      phosphate groups are involved in the formation of a catalytically active complex
      of (ADP-ribose) polymerase with DNA.

PMID- 1391207
TI  - [Interaction of human thrombin I fragment, prethrombin I, and alpha-thrombin with
      tissue thromboplastin].
AB  - The binding of 125I-labeled prothrombin fragment I. prethrombin I and alpha
      thrombin to native and papain-treated tissue thromboplastin in the presence of
      CaCl2 of EDTA was studied. The experimental curves plotted in the Scatchard
      coordinates testify to the presence in thromboplastin of two types of fragment I
      binding sites: those with a high (Kd = 7.6 x 10(-6) M) and moderate (Kd = 1.3 x
      10(-8) M) binding affinity. The parameters of fragment I binding and their
      changes reproduced, for the most part, the mode of prothrombin binding observed
      in previous studies. The experimental results provide indirect evidence in favour
      of a hydrophobic role of Ca(2+)-dependent binding of prothrombin fragment I to
      thromboplastin. The binding of prethrombin I was nonspecific and Ca(2+)
      independent, whereas alpha-thrombin showed a relatively high level of nonspecific
      electrostatic binding which was competitively inhibited by Ca2+. Thromboplastin
      proteins interacted (both directly and in a Ca(2+)-independent fashion) with all
      the prothrombin derivatives under study.

PMID- 1391208
TI  - [Inhibition of pyruvate kinase of bovine adrenal cortex by ATP: the role of
      magnesium].
AB  - The effect of ATP on bovine adrenal cortex pyruvate kinase has been studied. ATP
      is a competitive inhibitor of the enzyme, the Ki being 3.2 mM. Based on the
      efficiency of tryptophan fluorescence quenching, it was concluded that the
      magnesium complex of ATP is a true enzyme inhibitor. The role of Mg2+ in the
      inhibition process consists in the formation of a bridge between the enzyme and
      ATP. The ATP-dependent mechanism of pyruvate kinase inhibition is a potential
      physiological regulator of the enzyme determining the lower threshold of its
      sensitivity in vivo.

PMID- 1391209
TI  - [Gangliosides and antibodies to gangliosides in blood serum].
AB  - The concentration and composition of gangliosides from normal and pathological
      blood serum of animals and man are reviewed. Data concerning the elevation of the
      ganglioside content in the serum under malignization are summarized. The
      appearance of ganglioside-specific antibodies in some pathological states is
      described. The possible influence of changes in the serum ganglioside content and
      composition on immunity is discussed.

PMID- 1391210
TI  - [Mechanism of inhibiting the cytochrome P-450-dependent monooxygenase system in
      liver with fluorocarbons].
AB  - The inducer of the liver monooxygenase system perfluorodecalin added to
      microsomes as a submicron emulsion forms an enzyme-substrate complex with
      cytochrome P-450. The K(app) values for the perfluorodecalin binding to
      cytochrome P-450 in microsomes isolated from the livers of control and
      phenobarbital-treated rats are 5 x 10(-5) M and 2.3 x 10(-6) M, respectively.
      Perfluorodecalin competitively inhibits the binding of substrates to cytochrome P
      450 and decreases the rates of monooxygenase reactions. Perfluorodecalin
      extrusion from the active center of cytochrome P-450 occurs when an excess of
      perfluorocarbons non-interacting with cytochrome P-450 is added to microsomes.
      There is a significant vagueness in the rates of various monooxygenase reactions
      because of simultaneous induction and inhibition of monooxygenase enzymes after
      perfluorodecalin administration to rats. The data obtained are consistent with
      the hypothesis that constitutive forms of cytochrome P-450 are primary receptors
      for xenobiotic-inducers of phenobarbital-type cytochrome P-450 isoforms.

PMID- 1391211
TI  - [Purification and properties of GTP-cyclohydrolase from Bacillus subtilis].
AB  - Highly purified GTP-cyclohydrolase was obtained by fractionation of cell extracts
      with ammonium sulfate, ion-exchange and hydrophobic chromatography. The N
      terminal amino acid sequence and amino acid composition of the protein were
      determined. According to SDS-PAGE data, the molecular weight of the enzyme is 45
      kDa. The active enzyme has several isoforms separable by native electrophoresis.
      The maximal enzyme activity is determined at 1.5 mM Mn2+; 70% of enzymatic
      activity is detected with Mg2+. The enzyme is inhibited by heavy metal ions and
      chelators and is inactive in the absence of thiol-reducing agents. The enzyme
      activity is detected in a broad range of pH with a maximum at pH 8.2. The
      pyrimidine product of the GTP-cyclohydrolase reaction. 2.5-diamino-6-hydroxy-4
      ribosylaminopyrimidine-5'-phosphate was purified and identified. Another product
      of this reaction is pyrophosphate.

PMID- 1391212
TI  - [Rat liver antioxidant defense mechanism to the action of aromatic amines].
AB  - The effects of diaminobiphenyl, biphenylamine and tetraaminobiphenyl on lipid
      peroxidation and antioxidant protective mechanisms in the subcellular fractions
      of rat liver have been studied. It was found that activation of lipid
      peroxidation plays a crucial role in the manifestation of hepatotoxic activities
      of diaminobiphenyl and biphenylamine, this effect being due to the decrease of
      the protective activity of the antioxidant system during intoxication by these
      compounds. Tetraaminobiphenyl does not influence the rate of lipid peroxidation.
      It is concluded that structural differences determine the differences in the
      mechanisms of adaptation of the antioxidant system to the effect of aromatic
      amines.

PMID- 1391213
TI  - [The binding of SSB-proteins with DNA in chromatin of Ehrlich ascites carcinoma
      cells].
AB  - Using UV-induced cross-linking between proteins and DNA, the contacts between
      single-stranded DNA-binding proteins (SSB proteins) and chromatin DNA have been
      demonstrated. Ehrlich ascites tumour DNA was labeled in vivo by inoculation of
      tumour-bearing mice with 3H-thymidine. The cells were irradiated with the UV
      light dose of 3000 J/m2, destroyed in a Triton X-100-containing hypotonic medium,
      and separated by centrifugation into the extrachromatin fraction and chromatin.
      Chromatin DNA was digested with DNAase 1, and the chromatin proteins were
      extracted with 2 M NaCl-polyethyleneglycol. SSB proteins from the extrachromatin
      fraction and chromatin were purified. Only SSB proteins from UV-irradiated cell
      chromatin appeared to possess a high specific radioactivity which exceeded 7.5
      fold that of non-irradiated cells. There were no differences between chromatin
      SSB proteins in control and irradiated cells as could be evidenced from SDS
      electrophoresis data. It is assumed that in irradiated cells SSB proteins of DNA
      digested chromatin are covalently cross-linked with DNA fragments.

PMID- 1391215
TI  - [Analysis of the quaternary structure of secreted repressible acid phosphatase
      from the yeast Saccharomyces cerevisiae].
AB  - The structural organization of extracellular repressible acid phosphatase from S.
      cerevisiae has been studied. The existence of multiple acid phosphatase forms
      with isoelectric points at pH 4.1-4.8 has been confirmed by isoelectrofocusing.
      The molecular masses of three acid phosphatase isoforms (56, 57-59, and 60 kDa)
      obtained after enzymatic deglycosylation correlate with the data obtained
      previously during the analysis of translation products in cell-free systems.
      Electron microscopic studies revealed that the acid phosphatase molecule has a
      square shape and is made up of four identical subunits with molecular masses of
      about 125 kDa.

PMID- 1391214
TI  - [Modification of a disulfide in the hinge region of rabbit IgG and study of the
      interaction of polyvalent ferritin antigen, protein A, and anti-IgG].
AB  - Since immunoglobulins are used in a vast variety of immunoassays, the problem of
      obtaining antibodies with enhanced antigen-binding activity is of great
      importance. In order to discriminate between putative approaches to activating
      antibody modification, some functional characteristics of rabbit IgG modified at
      the hinge disulfide by three reagents: iodoacetamide, N-ethylmaleimide, and 2.2'
      dipyridyl disulfide, have been studied. As can be judged from gel-permeation
      chromatography data, the molecular sizes of modified rabbit IgG were slightly
      increased in comparison with the native protein. Using enzyme immunoassay, it was
      shown that modification by each of the above reagents results in the same degree
      of activation of the antibody binding to the protein polyvalent antigen-human
      ferritin, due to the increase in segmental flexibility, i.e., Fab motion around
      the Fo fragment of IgG. The type of concentration dependencies of antigen binding
      suggest that another determinant stimulating the antigen binding in addition to
      the increase in segmental flexibility, can be attributed to intra- or interdomain
      flexibility of domains constituting the Fab fragments. Using protein A and anti
      IgG as conformational probes for the antibody Fo fragment, the conformation and
      conformational dynamics of both CD2 domain epitopes and the switch region between
      the CD2 and CH3 domains have been shown to be essentially unaffected by
      modification.

PMID- 1391216
TI  - [Polyfunctional enzymes].
AB  - The properties of enzymes possessing several autonomous functions distributed
      among the domains of the polypeptide chain are considered. Three types of such
      proteins have been characterized: (i) bifunctional enzymes catalyzing consecutive
      reactions of metabolism: (ii) enzymes capable of catalyzing different reactions
      that are not consecutive and, (iii) enzymes catalyzing oppositely directed
      reactions. Possible advantages of various reactions catalyzed by the same protein
      are discussed.

PMID- 1391217
TI  - [Successes in studying the physiological activity of terpenoids and steroids].
AB  - Data concerning the structure and function of prenyl proteins and peptides of
      fungi and animals are reviewed. There exist proteins that are posttranslationally
      modified by thioether-linked farnesyl- or geranylgeranyl groups; the modification
      affects the cysteine residue near the C-terminus. Prenylation increases
      hydrophobicity and is expected to promote protein binding to membrane lipids or
      other hydrophobic proteins. Isopentenyl-adenylated proteins mediate isoprenoid
      control over DNA synthesis and are involved in regulation of cell proliferation
      in animals. Sterols of fungi and plants play a role in regulation of the membrane
      structure as well as in proliferation. The significance biologically active
      terpenoids for biotechnology, medicine, and agriculture is discussed.

PMID- 1391218
TI  - [Structure-functional properties of eukaryotic aminoacyl-tRNA synthetase].
AB  - Data on structural and functional peculiarities of eukaryotic aminoacyl-tRNA
      synthetases (structure, supermolecular organization, and localization in
      eukaryotic cell) are reviewed. The functional significance of aminoacyl-tRNA
      synthetase association with high molecular weight complexes and other cellular
      components is discussed.

PMID- 1391219
TI  - [Interaction of lactate dehydrogenase with structural cell components: possible
      physiological significance].
AB  - Reversible binding of cytoplasmic enzymes to structural elements of the cell is
      one of mechanisms of in vitro regulation of enzyme properties. The results on
      lactate dehydrogenase interactions with myofibrillar proteins and membranes and
      the changes in enzyme properties induced by these interactions (modification of
      kinetic parameters and stability) are analyzed. A hypothesis is proposed
      concerning the functional role of reversible lactate dehydrogenase interactions
      with structural components of the cell during glycolysis activation.

PMID- 1391220
TI  - [Nuclear proteoglycans from mouse liver cells: isolation and identification].
AB  - Proteoglycans (PG) have been isolated from mouse liver nuclei and identified.
      Nuclear PG are represented by various classes: i) PG containing dermatan sulfate
      (DS) chains; ii) PG containing heparan sulfate (HS) chains and, apparently, iii)
      mixed PG whose protein core contains both DS and HS chains.

PMID- 1391221
TI  - [Protein synthesis during hyperthermia in ground squirrels].
AB  - The intensity of [14C]leucine incorporation into heart, liver, brain, muscle, and
      blood plasma protein in gophers under deep artificial hypothermia has been
      studied. It was shown that the intensity of protein synthesis decreased sharply
      under these conditions. Insignificant incorporation of [14C]leucine into proteins
      was observed during the first two hours after the onset of hypothermia and then
      ceased completely.

PMID- 1391223
TI  - [Nonphysiological redox-agents are reduced at the binding center of NADP(H)
      glutathione reductase].
AB  - Studies of the acceptor reductase reaction of yeast glutathione reductase (EC
      1.6.4.2) revealed that the competitive inhibitors for NADPH, 2',5'-ADP and Br-
      decrease the rate constants for the enzyme oxidation by ferricyanide,
      phenanthrene quinone, and juglone. A similar effect is observed when NADH which
      does not bind to the reduced enzyme is used as substrate. These observations
      support the hypothesis that non-physiological redox agents are reduced at the
      NADP(H)-binding center of glutathione reductase and that NADP(H) binding
      stimulates the reaction by displacing tyrosine-197 which protects FAD from the
      solvent.

PMID- 1391222
TI  - [Lipid biosynthesis and metabolism of native and acetylated low density
      lipoproteins in macrophages stimulated by zymosan in vivo and in vitro].
AB  - The effects of zymosan on lipid metabolism in mouse peritoneal macrophages (MPM)
      in vitro and in vivo were studied with special reference to the following
      parameters: i) 14C-oleate incorporation into cholesteryl esters (CE),
      triglycerides (TG), and phospholipids (PL) in MPM incubated with low density
      lipoproteins (LDL) and acetylated LDL; ii) cholesteryl-14C-oleate-acetyl LDL
      uptake and 125I-acetyl LDL degradation; iii) oxidative modification of LDL.
      Zymosan administered to mice caused significant stimulation of 14C-oleate
      incorporation into CE, TG, and PL with no effect on 3H-cholesterol (Ch)
      incorporation into CE or 3H-glycerol incorporation into TG and PL in MPM. The 14C
      oleate incorporation into cellular lipids was unaffected by 18-hour incubation of
      MPM with zymosan (100-500 micrograms/ml) but increased after incubation of
      unstimulated MPM with blood serum and peritoneal fluid harvested harvested from
      zymosan-treated mice. One possible explanation of this phenomenon is oleyl-CoA
      formation induction in cytokine-stimulated MPM in vivo. Zymosan decreased the Ch
      14C-oleate-acetyl LDL uptake, 125I-acetyl LDL degradation, and Ch esterification
      in the presence of acetyl LDL in MPM both in vitro and in vivo. An increase in Ch
      esterification after incubation of MPM with zymosan for 6-18 hours in the
      presence of LDL was accompanied by an increase in lipid peroxidation of LDL and
      its electrophoretic mobility. The data obtained suggest that the macrophage
      acetyl LDL receptor pathway may be inhibited by zymosan and that cytokines
      released from zymosan-stimulated cells may influence the generation of foam
      cells.

PMID- 1391224
TI  - [Selective solubilization and biochemical analysis of R. prowazekii outer
      membrane proteins].
AB  - Solubilization of proteins from total membranes (a mixture of cytoplasmic and
      outer membranes) of Rickettsia prowazekii, a typical gram-negative bacterium, was
      studied using three different detergents. It was shown that isolated outer
      membranes and sarkosyl-insoluble material contain major polypeptides of 134, 31,
      29.5 and 25 kDa as well as minor polypeptides of 78, 60, 42, and 17 kDa, while
      the total membranes--the same plus a great number of additional minor proteins.
      The material solubilized by octyl glucoside in the presence of MgCl2 contains
      exclusively major proteins (134, 31, 29.5, and 25 kDa). No differential
      solubilization takes place upon membrane treatment with octyl glucoside in the
      absence of Mg2+ or with Triton X-100. Rickettsial proteins are insensitive to
      trypsin in both whole cells and total membranes, unless the latter are
      presolubilized with octyl glucoside. Proteinase K degrades all of the total
      membrane proteins but only the 134 kDa polypeptide of whole cells. Upon
      immunoblotting predominantly the major outer membrane proteins (134, 31, and 20.5
      kDa) and, to a lesser extent, the minor proteins (60, 42, and 17 kDa) interact
      with human convalescent serum.

PMID- 1391225
TI  - [Serine proteinase from the archaebacterium Halobacterium mediterranei--an analog
      of eubacterium subtilisin].
AB  - A homogeneous serine proteinase was isolated from cultural filtrates of the
      extreme halophilic bacteria Halobacterium mediterranei 1538 using affinity
      chromatography on bacitracin-Sepharose, ultrafiltration and gel filtration on
      Sephadex G-75, with a 48% yield and 260-fold purification. The enzyme was
      completely inactivated by specific inhibitors of serine proteinases, PMSF and
      DFP, as well as by Hg2+ and PCMB. The enzyme activity was strongly dependent of
      NaCl concentration, the enzyme being inactivated below 0.75 M NaCl. Inactivation
      of the enzyme was also seen in the presence of 2-7% organic solvents. The pH
      optimum for Glp-Ala-Ala-Leu-pNA hydrolysis is 8.0-8.5; Km is 0.14 mM, kcat is
      36.9 s-1. The stability optimum lies at pH 5.5-8.0, temperature optimum is at 55
      degrees C. The enzyme molecular weight is 41,000 Da; pI is 7.5. The substrate
      specificity of the enzyme is comparable to that of secretory subtilisins; the
      extent of protein substrate hydrolysis is similar to that of proteinase K. The N
      terminal sequence of Halobacterium mediterranei serine proteinase, Asp-Thr-Ala
      Asn-Asp-Pro-Lys-Tyr-Gly-Ser-Gln-Tyr-Ala-Pro-Gln-Lys-Val-Asn- Ala- Asp-, reveals a
      50% homology with the aminoterminal sequence of Thermoactinomyces vulgaris serine
      proteinase. Hence, the serine proteinase secreted by halophilic bacteria may be
      considered as a structural and functional analog of eubacterial enzymes.

PMID- 1391226
TI  - [Thyroid hormone conjugates with rhodamine B as fluorescent ligands of human
      plasma transport proteins].
AB  - Conjugates of thyroxine (T4) and triiodothyronine (T3) with rhodamine B in which
      the hormone and the fluorescent dye are linked via a thiourea bond have been
      synthesized. These conjugates possess an ability to inhibit in a competitive
      manner the binding of [125I]T4 to three protein preparations: T4-binding globulin
      (TBG), apolipoprotein A-I (ApoA-I), and high density lipoprotein particles (ApoA
      I-HDL) isolated from human serum by T4-Sepharose 4B chromatography and further
      purified. The following values of association constants have been estimated: for
      the T4 derivative-3 x 10(7) M-1 (TBG), 4.1 x 10(5) M-1 (ApoA-I), and 4.2 x 10(5)
      M-1 (ApoA-I-HDL); for the T3 derivative-1.6 x 10(7) M-1 (TBG), 5.3 x 10(5) M-1
      (ApoA-I), and 5.4 x 10(5) M-1 (ApoA-I-HDL). The binding of rhodamine B-labeled
      thyroid hormones to TBG or ApoA-I do not alter significantly the parameters of
      rhodamine B chromophore absorption and fluorescence. The interaction of the
      conjugates with ApoI-HDL leads to a significant enhancement of the absorption
      intensity and a 3 nm blue shift in the absorption maximum as well as to a 1.5
      fold increase in the fluorescence band amplitude at 586 nm. Biological and
      fluorescent properties of T4 and T3 derivatives suggest that these compounds may
      be a useful tool in fluorescence studies of plasma binding protein-driven
      transport of thyroid hormones in model biological systems.

PMID- 1391227
TI  - Cell proliferation in the small intestine and colon of intravenously fed rats:
      effects of urogastrone-epidermal growth factor.
AB  - There is marked intestinal hypoplasia in the intestine of intravenously fed (TPN)
      rats. Recombinant urogastrone-epidermal growth factor (URO-EGF) reversed these
      changes by significantly increasing the length of the intestinal crypts. Crypt
      diameter, however, was not affected to the same extent. Few differences in
      labelling indices were seen between the orally fed and TPN groups, however, this
      was the consequence of the concomitant changes in crypt population. The number of
      mitoses and labelled cells per crypt, and thus the crypt cell production rates,
      were significantly decreased in the TPN group when compared to the orally fed.
      URO-EGF significantly increased both proliferative indices and the number of
      dividing cells per crypt. Crypt cell production in the small intestine was
      restored to those levels seen in the orally fed rats, moreover, labelling per
      crypt in the colon was increased to more than twice that of orally fed rats. The
      location of the mean labelling position and the half maximum labelling position
      followed the changes in crypt length in the small intestine, but to a lesser
      extent; thus the growth fraction was significantly increased in the TPN rats in
      comparison with the orally fed and the URO-EGF treated groups. Similar changes in
      these positions were seen in the colon, but the growth fraction was much reduced
      in the URO-EGF treated rats, as a consequence of the large increase in crypt
      length without a concomitant alteration in label distribution.

PMID- 1391228
TI  - Altered proliferative kinetics in PHA-activated human T-lymphocytes treated with
      the anti-HLA class I monoclonal antibody 01.65.
AB  - Anti-HLA class I monoclonal antibody (mAb) 01.65 inhibited phytohaemagglutinin
      (PHA)-induced human lymphocyte proliferation. The inhibitory effect was inversely
      correlated to the strength of the proliferative response. It was increased when
      lymphocytes were stimulated with suboptimal doses of PHA but it disappeared with
      supraoptimal doses. Proliferation inhibition was achieved by prolonging the cell
      cycle time and by slowing down its recruitment rate. The former effect was not
      restricted to the G1-phase but also included the S phase. These results support
      the idea that HLA class I molecules are important in the PHA-induced
      proliferation of human T-lymphocytes.

PMID- 1391229
TI  - Proliferative changes in two murine tumours in response to single or fractionated
      doses of X-rays.
AB  - Studies were carried out to investigate proliferative changes in two murine
      experimental tumours in response to radiation. Results were generated using
      bromodeoxyuridine labelling and flow cytometry. This study demonstrates the
      possible ambiguity of previous studies using tritiated thymidine in which
      inability to discriminate normal and tumour cell components in murine tumours may
      lead to different values for cell kinetic parameters. In particular, the sarcoma
      F appeared to have a growth fraction of 0.62 when all cells were considered; in
      reality the growth fraction of the tumour cells only (based on DNA content
      discrimination) was close to unity. Radiation, administered either as single or
      fractionated doses, caused little change in the proliferative characteristics of
      the sarcoma F tumour but had profound effects on the adenocarcinoma Rhodesia
      tumour. Major changes were the accumulation of cells in G2 for several days after
      the end of the radiation treatment in both tumours and a dramatic drop in
      labelling index of the Rhodesia tumour. In neither tumour was there any evidence
      to suggest an increase in tumour cell proliferation during or after the
      irradiations. The diploid cells within the sarcoma F tumour showed an initial
      depression of labelling index followed by a rapid increase overshooting the
      control labelling index at higher radiation doses. Much of the effects could be
      attributed to cell cycle delays.

PMID- 1391230
TI  - Cell cycle analysis of asexual stages of erythrocytic malaria parasites.
AB  - Intra-erythrocytic Plasmodium species can be stained with the DNA binding dye,
      Hoechst 33342, and the distribution of DNA content determined for parasite
      populations by flow cytometric measurement of fluorescence. Analysis of this
      distribution will determine the parasitaemia (percentage of erythrocytes
      infected), and the percentages of trophozoite infected red blood cells,
      polyparasitized (trophozoite) red blood cells, and schizont/segmenter infected
      red blood cells. This analysis is based on the hypothesis that the asexual
      parasites cycle with single G1 period, and effectively, a single S phase with no
      significant G2/M period except at schizogony when the genome DNA content is
      equivalent to 8 N or higher, dependent on the species. Data are presented to
      support this model.

PMID- 1391232
TI  - Systemic administration of recombinant interleukin-6 in mice induces
      proliferation of lymphoid cells in vivo.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine and has been shown to support the
      growth of T and B lymphocytes in the presence of mitogens in vitro. IL-6 can
      induce human natural killer (NK) and interleukin-2 (IL-2)-induced lymphokine
      activated killer cell (LAK) activity in vitro. It can also mediate antitumor
      effects in various murine models. In order to understand the mechanism of in vivo
      action, we have investigated the proliferation of lymphoid cells in vivo and the
      effects on NK, and LAK cell activities in response to IL-6 administration in
      mice. In vivo proliferation was measured by labeling the DNA of dividing cells
      with [125I]iodo-2'-deoxyuridine. C57BL/6 mice were injected ip with either IL-6
      or HBSS control two times a day for 3 days and in vivo proliferation was
      measured. For comparative purpose IL-2 was administered and in vivo effects were
      analyzed. IL-6 caused significant proliferation of cells mainly in the spleen,
      while, IL-2 caused proliferation in the lungs, liver, spleen, and kidneys.
      Pretreatment irradiation (500 rad) of mice abrogated the IL-6-induced
      proliferation indicating radiosensitive cells are involved. Furthermore, in vivo
      proliferation was not observed in young nude mice treated with IL-6. To
      investigate whether the proliferating cells were cytotoxic, we tested for LAK
      (vs. fresh MCA-102 tumor targets) and NK (vs. Yac-1 tumor targets) activities in
      the organs of mice treated with IL-6 or IL-2 by 4 h 51Cr-release assay. IL-2
      administration induced the generation of LAK activity and increased NK
      cytotoxicity in various organs, but IL-6 had no effect.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391231
TI  - Growth fraction measured using the comet assay.
AB  - Growth fraction, an important determinant of tumour response to therapy, was
      measured using a novel assay in WiDr human colon carcinoma cells grown as
      monolayers, spheroids, or xenografts. The assay is based on the fact that the
      anticancer agent etoposide produces DNA strand breaks in proliferating but not
      non-proliferating cells. Strand breaks were detected in individual cells using
      the alkaline 'comet' assay, and growth fraction was defined as the fraction of
      cells containing elevated numbers of DNA strand breaks. The specificity of the
      method for detecting proliferating cells was verified directly by allowing cells
      to incorporate bromodeoxyuridine (BrdUrd) into DNA, followed by exposure to
      etoposide and treatment of the comets with anti-BrdUrd antibodies. All cells
      stained with anti-BrdUrd antibodies were also damaged by etoposide. Similarly,
      growth fraction measured using Ki-67 correlated well with the new assay. The
      accuracy, speed and convenience of the comet assay for measuring growth fraction
      suggest that it may be useful for predicting response of human cancers to
      therapy.

PMID- 1391234
TI  - Adhesion molecules on MHC-nonrestricted lymphocytes: high density expression and
      role in oncolysis.
AB  - We have shown that interleukin-2 (IL-2) -activated adherent lymphocytes (A-LAK)
      display superior oncolytic activity against acute myelogenous leukemia (AML)
      blasts when compared to conventionally prepared lymphocytes with lymphokine
      activated killing (LAK) activity. The A-LAK activity was generated promptly and
      from donors whose lymphocytes did not display any LAK activity. In comparison to
      LAK, a higher percentage of A-LAK expressed the CD25 and HLA class II (HLA-DR)
      activation-associated structures and high density of HLA class I antigens. Most
      striking, however, was the observation that lymphocytes from A-LAK cultures
      consistently contained a high density of CD2, CD11a, and CD18 adhesion molecules,
      as indicated cytometrically by their "bright" fluorescence intensity. Three color
      flow cytometric analysis indicated that virtually all CD56+,CD3- natural killer
      (NK) and CD56+,CD3+ T cells in unstimulated, LAK and A-LAK populations displayed
      this "bright" phenotype, while most CD56-,CD3+ T cells (with the exception of the
      small proportion found in A-LAK) were of the "dim" phenotype. The A-LAK cultures
      also contained a higher percentage of lymphocytes expressing CD11b (CR3 receptor)
      and CD54 (ICAM-1) antigens. The CD11a, CD18, and partially CD2 molecules were
      important in the A-LAK cytolytic mechanism against AML, since blocking of these
      structures with monoclonal antibodies (MAb) significantly decreased the
      antileukemia effect. Additionally, the ability of A-LAK to adhere to plastic was
      most strongly inhibited by anti-CD11a MAb and less, but significantly, by MAb
      against CD2, CD18, and CD56 molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391233
TI  - Employment of antipeptide antisera to distinguish two closely related cytokines
      induced in human T cells.
AB  - AT464 and AT744 are two cytokines encoded by mitogen-induced genes from human T
      lymphocytes. These proteins belong to a family of structurally related
      chemotactic proteins associated with inflammation. By expression of their full
      length cDNAs in COS cells and in baculovirus-infected Sf9 cells, we found that
      pAT464 and pAT744 cDNAs represent secreted polypeptides of a molecular mass of
      about 8,000 and 11,000 Da, respectively. Biochemical characterization of these
      proteins has been persued through polyclonal antisera, which were derived to
      synthetic peptides. Using these sera for Western blotting analyses the
      recombinant AT464 and AT744 proteins could be detected as secreted products from
      transfected COS cells and from baculovirus-infected Sf9 cells. Similarly the
      native proteins could be detected in the supernatants of activated human
      peripheral blood T cells. The recombinant and the T cell-secreted AT464 and AT744
      proteins appear to be identical as judged by their mobility by SDS-PAGE and by
      their reactivity with the rabbit polyclonal antisera.

PMID- 1391235
TI  - Interleukin-6 production by human melanoma cell lines.
AB  - We examined the expression of interleukin-6 (IL-6) by 12 established human
      melanoma cell lines. Two constitutively produced low levels of IL-6 protein, as
      measured by enzyme-linked immunosorbent assay. Cells from these two lines, as
      well as those from two non-IL-6-producing cell lines, contained IL-6-specific
      mRNA as demonstrated by Northern hybridization. Treatment of the two IL-6
      producing melanoma cell lines with interleukin-1 beta, tumor necrosis factor
      alpha, or phorbol myristate acetate caused a marked increase in IL-6 production.
      These induction signals failed to stimulate IL-6 production in the nonproducing
      cells, even those that expressed IL-6 mRNA. IL-6 did not appear to act as an
      autocrine growth factor since the addition of exogenous human recombinant IL-6 or
      polyclonal anti-IL-6 antibody did not alter cellular proliferation. The
      production of this multifunctional cytokine by tumors may play a role in tumor
      host interactions and this should be recognized in the design of biologic therapy
      trials.

PMID- 1391237
TI  - Use of biodegradable plates and screws in a rabbit model.
AB  - During the last decade, rigid internal fixation with miniplates and screws has
      gained widespread acceptance in the correction of both congenital and acquired
      craniomaxillofacial deformities. Recent studies have proposed that the currently
      employed metallic plates and screws may require removal because of potential
      facial growth restriction in growing children. Others have reported bone
      resorption under the plate due to stress shielding, infection, extrusion, and
      palpability in regions where there is minimal tissue coverage. Because these
      implants are radiopaque, they generate significant that interfere with
      radiological studies and with radiation therapy in patients undergoing treatment
      for malignancies. There is no question that the use of a biodegradable plating
      system would eliminate each of these potential or real problems, because
      stability is necessary only for a reasonably short period until the fracture
      segments have become united. We report the initial phase of a long-term study
      examining various materials that will be available for fabrication of a
      biodegradable plate and screw system. We evaluated a commercially developed
      biodegradable plate and screw system to treat zygomatic arch fractures in a
      rabbit model. Fractures were surgically created at the midpoint of each zygomatic
      arch. The experimental animals were then divided into three equal groups.
      Fractures in the first group were permitted to heal without any form of
      stabilization. In the second group, segments were secured with standard titanium
      plates and screws. Biodegradable plates and screws were employed for
      stabilization in the experimental group. Animals were then killed, and
      radiographs were obtained at 2, 4, 6, and 8 weeks.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391238
TI  - Effects of nerve growth factor on craniofacial onlay bone graft survival:
      preliminary findings.
AB  - A study was undertaken to evaluate the effects of nerve growth factor (NGF),
      which had previously demonstrated bone formation around mandibular nerve
      regenerates, on resorption of onlay bone grafts to the rabbit skull. Iliac grafts
      were onlayed on the parietal bone bilaterally and immobilized with wire ligatures
      in 15 animals. NGF and a control solution were introduced into the grafts through
      subcutaneous osmotic pumps. After 60 days, graft survival was compared by
      weights, histology, and fluorochrome labels. NGF-treated grafts were
      characterized by an average of 88.4% weight retention, preservation of the outer
      cortical plate with firm fixation to the underlying calvarium, and fluorescent
      labels localized to the inner cortex. Conversely, control grafts had an average
      weight retention of 42.8% (p < 0.01), nearly complete outer cortical plate loss
      with increased mobility of the residual inner cortex, and a lack of fluorescence
      in any part of the grafts. Despite the incongruous name, NGF exhibited a
      beneficial effect on onlay bone graft volume maintenance in this study. Although
      the mechanism and the long-term effects are unknown, inhibition of graft
      resorption rather than enhancement of bone formation is suggested.

PMID- 1391236
TI  - Regulation of freshly isolated, IL-4-producing T cells: IFN-gamma-sensitive and 
      resistant cells.
AB  - Cytokine responsiveness of interleukin-4 (IL-4)-producing T cells (IL-4p) during
      primary in vitro stimulation was investigated. Freshly isolated T cells were
      stimulated with anti-CD3 epsilon antibodies in the presence of macrophages. Using
      limiting dilution analysis, we found that IL-4p were not detected when endogenous
      IL-2 activity was blocked with anti-IL-2 antibodies. These data support previous
      observations that IL-4p require IL-2 for induction, and further indicate the
      presence of macrophages was not sufficient to overcome the requirement for IL-2.
      The effects of IFN-gamma on IL-4p were studied in this system. Addition of
      exogenous IFN-gamma decreased the frequency of IL-4p but did not completely
      inhibit induction of these cells. Furthermore, blocking endogenous IFN-gamma
      during stimulation resulted in a 2- to 4-fold increase in the frequency of IL-4p
      detected. These data demonstrate the novel finding that both IFN-gamma-resistant
      and IFN-gamma-sensitive IL-4p were present in freshly isolated T cell
      populations. Thus, during early in vitro culture, there were at least two types
      of IL-4p, both of which require IL-2. These data indirectly support a current
      model of Th ontogeny as defined by cytokine production patterns, and extend the
      model to include cytokine responsiveness.

PMID- 1391240
TI  - Maternal discourse features used with language-normal preschoolers with facial
      deformities.
AB  - Discourse features of 10 mothers of language-normal preschool children with
      repaired cleft palates were examined. Mothers had been provided training in
      infant stimulation. Fifty-six percent of the communication initiations within the
      mother-child dyads were made by the mothers. That level of responsibility for
      continuity of communication resembles the percentage of discourse initiation
      reported for mothers of language-normal children without orofacial clefts. All
      categories of utterance types were used by the subjects; a predominance was found
      among attention-getters and indirect directives. Distribution of discourse
      features appears to differ from that reported for mothers of both language-normal
      and language-impaired children who do not have orofacial clefts.

PMID- 1391239
TI  - Clinical experiences with patients with facial bone deformities associated with
      hemifacial microsomia.
AB  - Eighteen adult patients with hemifacial microsomia were treated with a
      combination of skeletal and augmentation surgery. Three typical cases are
      presented. In principle, skeletal and augmentation surgery have recently been
      performed in combination in a single stage. Groin flaps and scapular or scapular
      ostocutaneous flaps have mainly been employed for augmentation surgery.

PMID- 1391242
TI  - Rigid fixation in orthognathic surgery: a personal appraisal.

PMID- 1391241
TI  - Surgical correction of unilateral lambdoid synostosis: occipital rotation flap.
AB  - Virchow (1851) is credited with initially describing calvarial development
      following premature closure of individual sutures. He noted that resultant
      compensatory growth occurred perpendicular to the fused suture, resulting in
      asymmetrical calvarial development. Lambdoid synostosis, whether unilateral,
      bilateral, or associated with other cranial fusions, is reasonably uncommon.
      Previous authors report an incidence of less than 10% of all reported cases of
      premature fusion of the calvarial or skull base sutures. We report 27 patients
      (20 boys, 7 girls) ranging in age from 3 months to 8 years with unilateral
      lambdoid craniosynostosis followed over a three-year period. In 19 patients,
      calvarial reshaping was performed by repositioning a parietooccipital bone flap
      stabilized with lag-screw fixation to provide an increased radius of curvature to
      the affected area and to reestablish the resultant craniectomy between the
      parietooccipital junction and into the posterior fossa retromastoid occipital
      bone as an appropriate site for growth. Indications for one-stage calvarial
      reshaping included untreated lambdoid stenosis in older children or a failed
      simple lambdoid synostectomy after approximately 18 months. Each child
      experienced significant improvement in calvarial shape and ipsilateral ear
      position. Although we had no operative complications, two children underwent a
      second outpatient procedure for removal of hardware palpated by their parents.

PMID- 1391243
TI  - The course of the inferior alveolar neurovascular canal in relation to sliding
      genioplasty.
AB  - The anterior course of the inferior alveolar neurovascular canal was determined
      in 52 hemimandibles using high-resolution radiographs. Significant variability
      was found in its course. It was noted that if the osteotomies for sliding
      genioplasty were performed at least 6 mm below the inferior border of the mental
      foramen, injury to the mental nerve would be reduced.

PMID- 1391245
TI  - The role of research in craniofacial surgery.

PMID- 1391244
TI  - Comparison of inorganic bovine bone mineral particles with porous hydroxyapatite
      granules and cranial bone dust in the reconstruction of full-thickness skull
      defect.
AB  - Twenty adult rabbits were used to evaluate the biocompatibility and
      osteoconductivity of Bio-Oss, an inorganic bovine bone mineral, in the
      reconstruction of full-thickness skull defects. Skull defects were treated with
      either autogenous bone dust, porous hydroxyapatite granules, Bio-Oss particles,
      or were left untreated as controls. Histological examination of decalcified
      sections showed incorporation of Bio-Oss into the host tissue without a
      significant inflammatory reaction. Measurement of the profile area occupied by
      the bone revealed that Bio-Oss, hydroxyapatite, and the control had the same
      amount of bone ingrowth, whereas autogenous bone dust produced a greater amount
      of bone (p < 0.01). We conclude that Bio-Oss, like porous hydroxyapatite, has
      sufficient osteoconductive properties and can also be used as a bone substitute
      material.

PMID- 1391246
TI  - Immediate unrestricted feeding of infants following cleft lip and palate repair.
AB  - Postoperative feeding regimens after cleft lip and palate repair continue to be a
      controversial issue. This study was designed to test the feasibility of immediate
      unrestricted feeding after lip and palate closure with attention to operative
      outcome or complications. A retrospective analysis of two feeding protocols
      involved 80 infants with both unilateral and bilateral defects. Protocol A
      utilized tube and syringe feedings, and protocol B utilized unrestricted bottle
      or breast feedings. There were no instances of lip or palate wound complications
      in the unrestricted group. We conclude that immediate unrestricted feeding may be
      instituted safely, thus improving and simplifying postoperative management after
      cleft lip and/or palate repair.

PMID- 1391247
TI  - Hypoglossia-hypodactyly syndrome in a Brazilian child: clinical and surgical
      aspects.
AB  - We describe a Brazilian child born with the hypoglossia-hypodactyly syndrome,
      complicated by bands joining the maxilla to the mandible. Clinical findings are
      presented, along with the surgical repair procedure.

PMID- 1391248
TI  - Transoral approach to tumors of the clivus: report of two cases.
AB  - A transoral approach was used in 2 patients with tumors of the clivus, chordoma,
      and fibrochondro-chordosarcoma. Choice of the approach was based on data provided
      by craniofacial examination, radiographic examinations, magnetic resonance
      imaging, computed tomographic scans, and vertebral angiography, all of which
      suggested tumor involving the oropharynx and nasopharynx, with destruction of the
      clivus bone structure. This report demonstrates the feasibility of the transoral
      approach.

PMID- 1391249
TI  - Transmylohyoid oroendotracheal intubation: a novel method.
AB  - Anesthetic management of patients with multiple trauma of the face or those
      undergoing multiple facial osteotomies is problematic perioperatively, because
      anesthetists and surgeons fight for the same space. A novel method is
      demonstrated with use of a nylon flexometallic tube carried across the mylohyoid
      muscle (floor of the mouth).

PMID- 1391250
TI  - A quick technique for harvesting cranial bone grafts.
AB  - A simple technique is presented for quick harvesting of cranial bone in patients
      who require limited amounts of bone to cover defects in the craniofacial area.
      The major principle involved is to stay within the same anatomical region. For
      bigger defects, larger incisions and different techniques are usually used.

PMID- 1391251
TI  - Aggressive surgical management of sleep apnea syndrome in the syndromal
      craniosynostoses.
AB  - Obstructive sleep apnea syndrome (OSAS) frequently develops in patients with
      craniosynostosis and associated midfacial stenosis. In the past, conservative
      measures or tracheostomy have been used to manage this condition. Although the
      course of OSAS in these patients is multifactorial, a major factor is the marrow
      nasopharyngeal space. Aggressive surgical intervention to enlarge the
      nasopharyngeal space can reduce the severity of OSAS and therefore avoid the need
      for tracheostomy. Surgical approaches include adenotonsillectomy,
      uvulopalatopharyngoplasty, and midface advancement.

PMID- 1391252
TI  - Intrauterine brain damage in nonimmune hydrops fetalis.
AB  - Nonimmune hydrops fetalis has been described in a large number of pathological
      conditions, but brain aspect has been poorly explored. We report the
      neuropathological findings in a series of 38 fetuses and neonates with anasarca
      of various origin. Fourteen fetal cerebral ultrasonograms were available; 8
      presented some abnormalities. On brain examination, 23 cases showed hypoxic
      ischemic lesions. The white matter was the main site of damage that consisted in
      classical leucomalacia or other features such as: astrocytic glial reaction,
      microcalcifications and microthromboses either as isolated finding or in
      association. Anoxic neuronal damage was much less frequent. Anemia,
      hypoprotidemia and cardiac failure with hypotension, which often occur in hydrops
      fetalis, may account for brain perfusion failure and hypoxic-ischemic changes.

PMID- 1391253
TI  - The fibrinolytic system in the newborn: role of histidine-rich glycoprotein.
AB  - The fibrinolytic system controls fibrin deposition and its clearance. The
      efficacy of this system can be evaluated by plasminogen concentration
      determinations and by the behavior of factors such as histidine-rich glycoprotein
      (HRG) which controls plasminogen activation and alpha 2-antiplasmin which
      controls plasmin activity. Circulating plasminogen levels are decreased in the
      neonatal period. We studied factors affecting fibrinolysis in neonates and
      observed that an important reduction in HRG accompanied the reduced circulating
      plasminogen levels, with the result that 85% of circulating plasminogen was not
      bound to HRG and was thus free for binding to fibrin and for activation to
      plasmin. This condition is consistent with the increased fibrinolytic activity
      secondary to the "clotting activation' observed in the neonatal period
      particularly on the 1st day of life.

PMID- 1391254
TI  - Mode of delivery, plasma catecholamines and Doppler-derived cardiac output in
      healthy term newborn infants.
AB  - Umbilical cord arterial and venous concentrations of epinephrine, norepinephrine
      and the catecholamine metabolites 3,4-dihydroxyphenylglycol and 3,4
      dihydroxyphenylacetic acid were determined in 41 healthy newborn infants
      delivered vaginally, vaginally with epidural analgesia, by cesarean section under
      general anesthesia or by cesarean section under epidural anesthesia. Doppler
      derived cardiac output and arterial blood pressure were repeatedly measured
      during the first 48 h of life. There were fairly small differences in umbilical
      arterial and venous plasma concentrations of epinephrine and norepinephrine
      between the groups, with the highest levels of norepinephrine in infants
      delivered vaginally without analgesia (about 10 times as high as in the cesarean,
      general anesthetized group). No significant differences were found in the
      metabolite concentrations. Doppler-derived cardiac output and heart rate
      decreased in all groups during the study period and, in spite of increased
      catecholamine levels in the vaginally delivered infants, the differences between
      the groups were marginal. Healthy term infants with no signs of asphyxia were
      well prepared for a normal hemodynamic adaptation irrespective of mode of
      delivery or mode of obstetric anesthesia/analgesia.

PMID- 1391255
TI  - Sympathoadrenal activity in preterm infants during the first five days of life.
AB  - We measured plasma concentrations of epinephrine (E), norepinephrine (NE), 3,4
      dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) as well
      as urinary concentrations of metanephrine (M), normetanephrine (NM) and 3-methoxy
      4-hydroxymandelic acid (MOMA) on day 2 and day 5 in preterm infants; gestational
      age less than 30 weeks (G less than 30; n = 16) and gestational age 30-34 weeks
      (G 30-34; n = 19). Concentrations of E (0.00-2.28 nmol/l) and NE (0.6-9.1 nmol/l)
      in plasma were much lower than those previously reported during preterm and term
      delivery. The E:NE ratio decreased from 1:10 on day 2 to 1:30 on day 5, and the
      M:NM ratio decreased from 1:4 on day 2 to 1:8 on day 5, indicating relatively
      higher catecholamine secretion from the adrenals than from the sympathetic nerve
      terminals in preterm infants during postnatal adaptation. Plasma concentrations
      of DOPAC and DHPG were significantly higher in G less than 30 than in G 30-34
      (DOPAC, p = 0.0494; DHPG, p = 0.0092), probably relating to a low urinary
      excretion rate of catecholamine metabolites in infants in G less than 30. Plasma
      and urinary concentrations of catecholamines and their metabolites varied
      considerably, and no significant correlations to postnatal events could be
      demonstrated.

PMID- 1391256
TI  - Levels of epidermal growth factor in human cord blood.
AB  - Levels of epidermal growth factor (EGF) in the cord serum of 13 full-term and 84
      preterm infants were measured using a radioimmunoassay. Detectable levels of
      immunoreactive EGF were present in the cord blood at 23 weeks gestation and rose
      gradually with increasing gestational age. EGF levels correlated significantly
      with birth weight and placental weight. In small-for-gestational-age infants with
      birth weights smaller than 3 SD below the mean, EGF levels were lower than those
      in appropriate-for-gestational-age infants. These results suggest that EGF may
      play a role in fetal growth, but low EGF levels may also be the result of growth
      retardation.

PMID- 1391257
TI  - Renal function in preterm infants during the first five days of life: influence
      of maturation and early colloid treatment.
AB  - We measured the influence of maturation and early freshly frozen plasma infusion
      (FFP) on renal function (day 2 and day 5) in preterm infants in intensive care;
      they were divided into two groups, those with gestational ages less than 30 weeks
      (G less than 30) and those with gestational ages of 30-34 weeks (G 30-34). A
      total of 35 infants was studied. The infants were randomly assigned to one of two
      treatment groups, one receiving FFP, the other not, yielding four study groups; G
      less than 30 and no FFP (8 infants), G less than 30 and FFP (8 infants), G 30-34
      and no FFP (9 infants) and G 30-34 and FFP (10 infants). The infants in the two
      FFP groups received FFP 10 ml/kg on days 1-3. FFP did not significantly influence
      creatinine clearance (CCr) or the urinary sodium excretion rate either in G less
      than 30 or G 30-34. CCr was significantly lower (p less than 0.001) and
      fractional urinary sodium excretion significantly higher (p less than 0.002) in
      infants of G less than 30 than in infants of G 30-34. Infants of G less than 30
      had significantly higher plasma potassium concentrations (p less than 0.01) than
      infants of G 30-34. Despite the low CCr and the high urinary sodium excretion
      rate, infants of G less than 30 had stable fluid and electrolyte balance.

PMID- 1391258
TI  - Effects of thiazide diuretics on the lipid profile of infants with
      bronchopulmonary dysplasia.
AB  - Hyperlipidemia has been reported in some infants with bronchopulmonary dysplasia
      (BPD) who received thiazides for extended periods. In this prospective,
      controlled trial, we studied 17 infants with BPD who received diuretic therapy
      and 26 control infants who did not receive diuretics. Plasma triglycerides, total
      cholesterol and high-density lipoprotein (HDL) cholesterol were measured
      enzymatically prior to onset of diuretic therapy in the study group of infants
      and on the day of recruitment into the study in control infants, and every 2
      weeks thereafter. Plasma low-density lipoprotein cholesterol concentrations were
      calculated. At the end of 4 weeks, plasma lipid concentrations were comparable in
      both groups of infants except for significantly higher plasma HDL cholesterol
      concentrations observed in infants who received chlorothiazide (39 +/- 15 vs. 30
      +/- 6 mg/dl, p less than 0.05). Short-term administration of chlorothiazide to
      infants with BPD is not associated with clinically significant changes in plasma
      lipid concentrations.

PMID- 1391259
TI  - Glucocorticoids and the development of neuronal function: effects of prenatal
      dexamethasone exposure on central noradrenergic activity.
AB  - Although glucocorticoids slow the development of most cell types, they have been
      hypothesized to promote the differentiation of catecholaminergic cells. In the
      current study, pregnant rats were given dexamethasone on gestational days 17, 18
      and 19, and the functional state of noradrenergic synaptic activity was assessed
      throughout postnatal development by measurements of transmitter levels and
      turnover, and receptor binding capabilities. Despite growth inhibition caused by
      dexamethasone, the steroid treatment had little or no effect on transmitter
      levels or receptor binding and accelerated the maturation of norepinephrine
      turnover in a regionally selective manner. Effects were most notable in the
      midbrain and brainstem, where turnover rose to maximum levels 1-2 weeks in
      advance of controls. Turnover also leveled off prematurely in the dexamethasone
      group, leading to deficits in the postweaning period and into young adulthood.
      Although similar patterns were obtained in other, later-developing regions, the
      effects were less consistent and robust; the smaller effects also extended to
      dopamine turnover. These results suggest that glucocorticoids have a specific
      promotional effect on the development of central catecholaminergic activity and
      that administration of exogenous steroids during critical periods of development
      can lead to lasting functional abnormalities.

PMID- 1391260
TI  - Bubbles and computer-aided image analysis for evaluation of surfactant
      inhibition.
AB  - Surfactant (Curosurf, diluted to 5 mg/ml) was suspended in normal saline with 3
      mM CaCl2 and mixed with different concentrations of albumin or fibrinogen. The
      samples were vortexed to generate microbubbles, and the equivalent circle
      diameter of these bubbles was determined with computer-aided image analysis.
      Bubbles in the original surfactant suspension had an average diameter of 27
      microns after 2 min, and their size increased only little during a 15-min period
      of observation. The diameter of bubbles generated in the presence of albumin (4
      or 40 mg/ml) or fibrinogen (4 mg/ml) was 4-5 times larger, indicating surfactant
      inhibition. We conclude that evaluation of microbubble stability with image
      analysis provides an objective and rapid assessment of surfactant inhibition, and
      we speculate that the method could also be used for quantification of surfactant
      activity in airway samples.

PMID- 1391261
TI  - Effectiveness of curosurf for severe respiratory distress syndrome: a case
      control study.
AB  - Randomized trials have proven that exogenous surfactant is effective in severe
      neonatal respiratory distress syndrome when strict entry criteria are applied. To
      evaluate efficacy of surfactant treatment in a clinical setting, we performed a
      case-control study. The outcome of the first 25 consecutive cases treated with
      porcine surfactant (Curosurf) was compared to that of 25 matched historical
      nontreated controls. Survival at discharge was significantly higher in surfactant
      treated cases than among controls (76 vs. 48%; p less than 0.05). No differences
      were found in other outcome parameters.

PMID- 1391262
TI  - Factors influencing morbidity and mortality in infants with severe respiratory
      distress syndrome treated with single or multiple doses of a natural porcine
      surfactant.
AB  - In an international multicenter trial infants with clinical and radiological
      signs of severe RDS (age 2-15 h, birthweight 700-2,000 g, mechanical ventilation,
      FiO2 greater than or equal to 0.6, no complicating disease) were randomized to
      receive either a single dose (n = 176) or up to three subsequent doses (n = 167)
      of a natural porcine surfactant (Curosurf). Using a logistic regression model,
      the effects of therapy, birthweight, sex, hospital and other clinical factors on
      survival and various outcome parameters were evaluated. Mortality (13 vs. 21%, p
      less than 0.05) and the incidence of pneumothorax (9 vs. 18%, p less than 0.01)
      were significantly lower in the multiple-dose group. Low birthweight, hospital
      allocation, low Apgar score and initial disease severity were associated with an
      increased mortality. Low birthweight, hypothermia (admission temperature less
      than 36 degrees C) and acidosis (pH less than 7.25) prior to surfactant treatment
      could be identified as risk factors for the development of intracranial
      hemorrhage.

PMID- 1391263
TI  - Surfactant administration and the cerebral circulation.
AB  - We have used two main techniques to investigate the effect of surfactant therapy
      on the cerebral circulation in 34 babies. Twenty-one babies were studied using
      near infrared spectroscopy and 13 had cerebral blood flow measured using a xenon
      clearance technique. Other measures recorded included amplitude integrated EEG,
      mean arterial blood pressure and central venous or oesophageal pressure. There
      was a marked depression in EEG activity lasting for 10-20 min after surfactant
      administration. Cerebral blood volume and cerebral blood flow were maintained in
      most infants in spite of a fall in mean arterial blood pressure. We conclude that
      factors other than cerebral ischaemia cause the transient disturbance in
      electrophysiologic activity.

PMID- 1391264
TI  - Modifications of surfactant phospholipid pattern in premature infants treated
      with curosurf: clinical and dietary correlations.
AB  - Neonatal respiratory distress syndrome (RDS) is characterized by an immature
      surfactant phospholipid pattern. We aimed to study the evolution of surfactant
      phospholipids over a 6-day period, before and after surfactant replacement
      therapy with Curosurf, and to investigate possible interactions with exogenous
      phospholipids administered during total parenteral nutrition (TPN). Seventeen
      premature infants with RDS were randomly assigned to receive TPN with lipids or
      without (glucose group). Both groups showed a similar evolution of the surfactant
      phospholipids. At day 6, the surfactant composition had changed towards a mature
      human surfactant pattern except for phosphatidylglycerol which remained low (1%),
      compensated for by a high phosphatidylinositol and phosphatidylserine proportion
      (13.3%), Phospholipid subcomponents in plasma remained unchanged in both groups.
      Plasma total cholesterol (151 +/- 18 vs. 113 +/- 6 mg/dl, p less than 0.05) and
      cholesteryl esters (172 +/- 20 vs. 113 +/- 9 mg/dl, p less than 0.01) were higher
      in the glucose than in the lipid group. Total calorie intake was significantly
      higher in the lipid group (85 +/- 4 vs. 64 +/- 6 kcal/kg.day, p less than 0.01).

PMID- 1391265
TI  - Lung mechanics (FRC and static pressure-volume diagram) after endotracheal
      surfactant instillation: preliminary observations.
AB  - Preliminary measurements of functional residual capacity (FRC) with the
      sulphurhexafluoride technique and static pressure volume diagrams were performed
      in newborn infants with respiratory distress syndrome receiving endotracheal
      instillation of natural porcine surfactant (Curosurf, 100 or 200 mg/kg). Within
      the first hour after surfactant treatment there was an increase in FRC and
      distensibility of the lungs persisting for 24-48 h.

PMID- 1391266
TI  - Pulmonary functional outcome at one year of age in infants treated with natural
      porcine surfactant at birth.
AB  - This prospective study was designed to assess pulmonary function (functional
      residual capacity, FRC; dynamic lung compliance, CLdyn; and total pulmonary
      resistance, RL) at 1 year of corrected age in infants with neonatal respiratory
      distress syndrome treated with natural porcine surfactant (Curosurf) (n = 13), as
      compared to nontreated control infants (n = 9). Values from 21 healthy infants of
      similar age served as reference. We found similar pulmonary dysfunction
      (decreased CLdyn, elevated RL) in both patient groups. These results suggest that
      surfactant replacement therapy does not affect pulmonary function at 1 year of
      age in infants who survive respiratory distress syndrome.

PMID- 1391267
TI  - Surfactant replacement therapy and the prevalence of acute retinopathy of
      prematurity.
AB  - To determine if surfactant replacement treatment is associated with an increase
      in the prevalence of retinopathy of prematurity (ROP) we studied 76 preterm
      babies who were treated with porcine surfactant (Curosurf) for severe respiratory
      distress syndrome from 1985 to 1990. Babies were first examined by indirect
      ophthalmoscopy at the equivalent of 32 weeks post-menstrual age and subsequently
      at 2-week intervals until discharge from hospital. Findings were documented
      according to the International Classification of ROP. Sixty-two (82%) babies
      survived to discharge, 7 survivors were not examined due to transfer elsewhere.
      Acute ROP developed in 14 (29%) of the 49 babies examined (7 stage I, 4 stage II,
      2 stage III, and 1 stage IV); one baby required cryotherapy. No baby of
      birthweight greater than 1,500 g developed ROP. The prevalence of ROP was similar
      to that reported for non-surfactant-treated very-low-birthweight babies. We
      conclude that Curosurf treatment does not increase the risk of acute ROP in
      surviving very-low-birthweight babies.

PMID- 1391268
TI  - Estimated costs of different treatments of the respiratory distress syndrome in a
      large cohort of preterm infants of less than 30 weeks of gestation.
AB  - Within a model cohort of 1,000 preterm infants of less than 30 weeks of
      gestation, the incidence and mortality of RDS change if corticosteroids are used
      prenatally and surfactant prophylactically or therapeutically after birth.
      Combined pre- and postnatal therapies give the best results: approximately 125
      extra survivors. Therapeutic surfactant administration even in combination with
      prenatal corticosteroids has cost implications because extra intensive care beds
      (7-11%) are needed. More special care places (12-24%) are required after each
      type of intervention. The estimated costs per extra survivor are the lowest for
      prenatal corticosteroid administration. The combination of corticosteroids
      prenatally and prophylactic surfactant postnatally seems to be most cost
      effective because it produces the greatest number of survivors and the lowest
      number of intensive and high dependency care days in hospital.

PMID- 1391269
TI  - Postnatal development of plasma-lipid-clearing enzymes (lipoprotein lipase,
      hepatic lipase and lecithin:cholesterol acyl transferase) and lipid profiles in
      suckling rats.
AB  - We examined the activity of plasma circulating lipoprotein lipase and hepatic
      lipase, lecithin:cholesterol acyl transferase (LCAT), as well as lipid profiles
      in Sprague-Dawley rats from 1 day until 29 days of age. Plasma lipoprotein lipase
      activity peaked between ages 5 and 15 days and decreased after weaning, while
      plasma hepatic lipase activity remained constantly low during the suckling period
      and increased after weaning. No statistically significant difference in LCAT
      activity was seen from birth until weaning. Plasma triglycerides, as well as free
      fatty acids, decreased significantly after birth. Total plasma cholesterol
      increased during the suckling period and decreased after weaning. HDL cholesterol
      increased after the first 10 days of life, and free cholesterol remained constant
      after an initial decrease from birth to the 5th day of life. In conclusion, the
      enzymes associated with the metabolism of triglycerides, cholesterols and
      phospholipids are well developed in the rat shortly after birth.

PMID- 1391270
TI  - Serum IgE concentrations in the neonatal period.
AB  - The aim of the present study was to evaluate the IgE-mediated response as a
      predictable index of immunosensitization to different types of feeding (breast
      milk, adapted formula, soya formula and serum protein hydrolyzate formula) in the
      first days of life. The study population included 231 newborns (128 males and 103
      females). There was a family history of atopy (at least 1 parent with an atopic
      disease) in 116 subjects at risk for allergy. 115 newborns were without any
      family history of atopy. The results showed significantly higher total IgE levels
      on the 4th day than in cord serum in the whole group of newborns. The same result
      was obtained comparing subjects at risk and controls separately. No significant
      difference was detectable between serum IgE levels in the cord blood of the four
      groups. Conversely, a significant increase in IgE levels between cord and 4th day
      blood in soya-fed and adapted-formula-fed babies was noticed. This increase did
      not occur in neonates fed breast milk and serum protein hydrolyzate.

PMID- 1391272
TI  - Transverse bone growth and cortical bone mass in the human prenatal period.
AB  - The prenatal development of the normal diaphysis of the human long bone was
      studied through postmortem radiographs in 60 stillborns and 86 newborns of 20-41
      weeks gestational age. Quantitative parameters were determined for the tibia,
      femur, and humerus. In all three long bones, significant positive correlations
      were found between the diaphyseal diameter, medullary diameter, cortical
      thickness, and cortical area, and the gestational age, body weight, body height,
      and bone length. No significant differences in any studied parameters were
      observed between males and females. In the tibia, the diaphyseal diameter grew
      more than in the femur and humerus. In these two latter bones, the medullary
      diameter growth rate was greater than the diaphyseal diameter growth rate, and
      thus the Barnett-Nordin index and percentage of cortical area showed mild but
      significant negative correlations with gestational age, body weight, body height,
      and bone length. The velocity of medullary diameter growth was similar (0.05
      mm/week) in all three long bones; however, the velocity of diaphyseal diameter
      growth was greater in the tibia (0.161 mm/week) than in the femur (0.142 mm/week)
      or humerus (0.129 mm/week). The diaphyseal growth rate decreased in the second
      half of the period studied in all three bones. This decrease was more striking in
      the humerus. Observed differences in diaphyseal growth among the long bones
      studied may be genetically determined in relation to its different postnatal
      functions.

PMID- 1391271
TI  - Gastric secretion in infants. Application to the study of sudden infant death
      syndrome and apparently life-threatening events.
AB  - Sudden infant death is a problem of paediatric public health which remains an
      unpredictable phenomenon of unknown aetiology. Many authors have discussed the
      role of a neurovegetative aetiology, the role of the vagus nerve being suspected
      above all. A biological approach to vagal tone was attempted by assaying
      intragastric pepsin and serum pepsinogen and calculating the ratio of pepsin to
      acid in control infants, and by assaying serum pepsinogen levels in infants
      having suffered an apparently life-threatening event (ALTE) or who died of the
      sudden infant death syndrome (SIDS). This study showed that the age of 2 months
      appears to be a turning point in the development of digestive secretions, an age
      when the risk of SIDS is at its peak, and that the rates of the selected
      biological markers are significantly higher in victims of SIDS or ALTE than in
      controls. The predictive value of these biological markers is currently under
      evaluation.

PMID- 1391273
TI  - Capillary (heelstick) versus venous blood sampling for the determination of
      glucose concentration in the neonate.
AB  - Various sites may be used to obtain blood (plasma) for the determination of the
      glucose concentration in the neonate. Because multiple sites may be sampled in
      the same neonate, it is important to determine the variability in blood glucose
      concentration which may result from such sampling. Since pain and mechanical
      forces may be different because of the method used to obtain the capillary
      (heelstick) blood compared to the venous specimen, the two sites were sampled,
      and the blood glucose concentration was determined simultaneously in 25
      asymptomatic well neonates whose mean birth weight was 2,562 +/- 152 g and whose
      gestational age was 35.5 +/- 1.5 weeks. There was a significant (p less than
      0.0001), but relatively weak correlation (r2 = 0.64) between capillary
      (heelstick) blood and venous blood relative to blood glucose concentration. When
      the capillary (heelstick)-venous glucose concentration difference was compared to
      the mean of the capillary (heelstick) and venous glucose concentrations, a
      difference of +/- 0.5 mM (9 mg/dl) was noted in 3 of 25 neonates. Appropriately
      obtained capillary (heelstick) blood samples provide measurement of blood glucose
      concentration which are variable compared to venous samples, but which are
      probably not significant physiologically.

PMID- 1391274
TI  - Consumption and production of amino acids by insulin-responsive cultured fetal
      rat hepatocytes: the particular case of serine.
AB  - The ability for 18-day fetal rat hepatocytes in primary culture to modify
      extracellular amino acid concentrations was studied between 24 and 48 h of
      culture. Most of the 19 amino acids tested were found to be taken up by the
      hepatocytes. However, serine and glutamate appeared in the 24-hour-conditioned
      medium to be twice as concentrated as in the fresh medium. The profile of net
      consumption or production of amino acids was unchanged when the medium was
      supplemented with essential amino acids. The use of [U-14C]glucose revealed that
      serine released in the medium was mainly formed from glucose. The presence of
      insulin (10 nM) did neither significantly modify the variations of amino acid
      concentrations in the medium nor 2-amino[1-14C]isobutyric acid uptake by the
      cells, while the hormone produced a 2-fold increase in glycogen labeling from [U
      14C]glucose. This study revealed that whatever the regulatory culture conditions
      considered a net serine production out of the cells occurred, which appears to be
      specific to the fetal stage.

PMID- 1391275
TI  - Transfer of 125I-albumin from blood to brain in newborn rats and the effect of
      hyperbilirubinemia on the transfer.
AB  - Transfer of albumin from blood into cerebellum and cerebrum was examined in
      postnatal rats. 125I-Albumin was injected into rats on day 3, 7, 14, 28 or 70.
      The ratio of albumin concentration in the cerebellum or in the cerebrum to that
      in the plasma 2 h after the injection, hereinafter termed the relative albumin
      level (RA), was calculated and used as a criterion for the albumin transfer. The
      RA in both the cerebellum and the cerebrum decreased with age, but plateaued
      between days 28 and 70. The level was significantly higher in the cerebellum than
      in the cerebrum on days 3 and 7. This was not observed, however, on days 28 and
      70. Significant correlations were indicated between 125I-albumin levels in the
      plasma and those in the cerebellum or cerebrum on days 7 and 14, but not on day
      28. No significant difference in the RA in the cerebellum and the cerebrum was
      detected between jaundiced homozygous Gunn rats and control nonjaundiced rats at
      all ages examined. These results demonstrated that albumin could enter the brain
      tissue from the blood at least until postnatal day 14 and that the endogenous
      bilirubin had no effect on the albumin transfer into the brain. The relationship
      between the immaturity of brain and the transfer of albumin into the brain was
      discussed.

PMID- 1391276
TI  - Antenatal ambroxol effects on surfactant pool size and postnatal lung function in
      preterm ventilated rabbits.
AB  - Following maternal treatments with 50 mg/kg/day ambroxol for 2 or 3 days before
      delivery at 28 days gestation, preterm rabbits were ventilated to evaluate lung
      function. Subsequently, surfactant saturated phosphatidylcholine (SatPC) pool
      sizes were measured. One half of the ambroxol treated and control rabbits were
      given surfactant at delivery. Although surfactant improved lung function
      comparably for control and ambroxol treated rabbits, ambroxol treatments did not
      change ventilatory pressure requirements, compliances, or the recovery of
      intravascular labeled albumin in the lungs. Ambroxol treatments tended to
      increase lung volumes as evaluated by pressure-volume curves. The ambroxol
      treatments significantly increased lung tissue SatPC by 22%, but there were no
      changes in alveolar SatPC pool values. These results do not indicate a large
      effect of ambroxol on lung function in preterm rabbits.

PMID- 1391277
TI  - An increased ability to generate hydrogen peroxide in certain polymorphonuclear
      leukocytes in neonates.
AB  - We performed a quantitative assay of the hydrogen peroxide generation in
      polymorphonuclear leukocytes using single cell analysis by flow cytometry. The
      study population included premature neonates (n = 10), term neonates (n = 28) and
      healthy adults (n = 29). The ability to generate hydrogen peroxide in neonatal
      polymorphonuclear leukocytes was totally reduced compared with adults, however,
      some polymorphonuclear leukocytes in neonates demonstrated highly accentuated
      hydrogen peroxide generation.

PMID- 1391278
TI  - Effects of early suckling of cesarean-born babies on lactation.
AB  - This study examines the effect of early suckling of mothers giving birth by
      cesarean section on milk ejection periods. Colostrum and milk ejection periods of
      20 mothers who suckled their infants early and those of 20 who suckled late and
      provided supplementary food to their infants were observed. The colostrum and
      milk ejection periods of the early-suckled compared to the late-suckled group
      showed a significant statistical difference. The results show that the chance of
      the infants born by cesarean section of being fed by maternal milk could be
      increased by early and regular suckling of the maternal milk.

PMID- 1391279
TI  - Defining seasonal affective disorder(s)

PMID- 1391280
TI  - Unimodal and crossmodal reactivity in autism: presence of auditory evoked
      responses and effect of the repetition of auditory stimuli.
AB  - Using auditory evoked responses, this work compares the reactivities to unimodal
      and crossmodal stimuli and the main neurocognitive functions most often disturbed
      in autism. With the aim of testing the hypothesis that the deficit in the ability
      to form crossmodal associations in autism is linked to a cognitive abnormality,
      auditory evoked responses to simple and to crossmodal (auditivo-visual) stimuli
      were recorded in 30 autistic children and compared with those of 30 normal and 30
      mentally retarded children. Relationships between electrophysiological reactivity
      and neurocognitive functions showed that the cognitive deficit in the ability to
      maintain crossmodal associations is preceded by a more elementary perceptive
      abnormality in autistic children.

PMID- 1391281
TI  - Controlled study of erythrocyte choline in Tourette syndrome.
AB  - Erythrocyte and plasma choline parameters were compared in children (n = 63),
      aged 6-18 years, suffering from Tourette Syndrome (TS), their parents (n = 57),
      their unaffected siblings (n = 38), and an adult control group (n = 57). Factors
      such as severity of illness, medication status, and gender had no effect on
      erythrocyte choline. TS patients showed elevations in erythrocyte choline level
      compared to controls. Furthermore, the erythrocyte choline concentration in TS
      patients with a history of TS or chronic motor tic disorder (CMT) in first-degree
      relatives showed a positive correlation with that of their parents (r2 = 0.6, p
      less than 0.03). Erythrocyte choline values in TS patients without such positive
      family history do not demonstrate a familial relationship. Positive history of TS
      or CMT in first-degree relatives accounts for the observation of elevated
      erythrocyte choline in unaffected siblings of TS patients. Age effects on
      erythrocyte choline were found in the TS patients only (r = -0.14, p less than
      0.04) and not in parents, siblings, or normal controls. A gender effect on plasma
      choline was noted with male levels 23% higher than in females. The present
      findings support the utility of erythrocyte choline as a marker for the familial
      expression of the TS diathesis.

PMID- 1391282
TI  - Suicidal behavior and growth hormone response to apomorphine test.
AB  - Several cerebrospinal fluid (CSF) studies have provided support for a possible
      role for the dopaminergic system as a biological correlate of suicidal behavior.
      Indeed, low CSF levels of the dopamine metabolite homovanillic acid (HVA) have
      been described in depressed patients with a history of suicide attempts. In this
      study, we assessed the dopamine receptor sensitivity in relationship to suicidal
      behavior by measuring growth hormone (GH) response to apomorphine 0.5 mg
      subcutaneously (sc) in 15 DSM-III-R (APA 1987) major depressive inpatients with a
      history of suicide attempts, compared to age-matched and gender-matched major
      depressive inpatients without a history of suicide. Patients with a history of
      suicidal behavior exhibited a significantly lower GH response to apomorphine than
      patients who never attempted suicide (t = 3.60, df = 1.28, p = 0.0012).
      Therefore, these results suggest that a blunted GH response to apomorphine could
      represent a biological marker of suicidal behavior.

PMID- 1391283
TI  - Psychotic symptoms resulting from intraventricular infusion of dopamine in
      Parkinson's disease.

PMID- 1391285
TI  - Aggression and hostility in anabolic steroid users.

PMID- 1391284
TI  - Estimating daily urine volume in psychiatric patients: empiric confirmation.

PMID- 1391286
TI  - Methimazole in treatment-resistant depression.

PMID- 1391287
TI  - Evidence of impaired smooth pursuit eye movement performance in crack cocaine
      users.

PMID- 1391288
TI  - Growth hormone response to TRH in families multiply affected with schizophrenia.

PMID- 1391289
TI  - Role of the dopaminergic system in depression.
AB  - A hypothesis implicating dopamine in depression was proposed over 15 years ago
      (Randrup et al 1975). The identification of multiple new subtypes of dopamine
      receptors and evolving views regarding the function of the dopamine systems in
      the brain require a reexamination of this hypothesis. Results from studies in
      depression, Parkinson's disease, and animal models of depression suggest a
      deficiency of dopamine in depression. Dopamine precursors, dopamine agonists, and
      dopamine reuptake inhibitors show therapeutic efficacy in depression.
      Electroconvulsive therapy (ECT) and standard pharmacological antidepressants
      enhance dopamine function. Studies using receptor-specific drugs in clinical
      trials and neuroimaging studies are needed to further clarify the role of
      dopamine in depression.

PMID- 1391290
TI  - A single oral dose challenge of buspirone does not affect memory processes in
      older volunteers.

PMID- 1391292
TI  - Hypomania induced by fluoxetine?

PMID- 1391291
TI  - Treatment of hypomania following neuroleptic malignant syndrome.

PMID- 1391293
TI  - Endocrine, cardiovascular, and behavioral responses to clonidine in patients with
      panic disorder.
AB  - We examined adrenergic regulation in patients with panic disorder by challenging
      10 patients and 14 age-matched and sex-matched controls with intravenous
      infusions of clonidine hydrochloride (2 micrograms/kg), an alpha 2-adrenoreceptor
      agonist. Growth hormone, 3-methoxy-4-hydroxyphenylglycol (MHPG), blood pressure,
      heart rate, and behavioral (anxiety, sedation) responses were monitored. The data
      replicated the previously reported finding of blunted growth hormone (GH)
      responses to clonidine in patients with panic disorder. Reported abnormalities in
      MHPG, cardiovascular, and behavioral responses of panic patients to clonidine
      infusion were not replicated. The robustly blunted GH response to clonidine in
      panic patients supports the adrenergic dysregulation hypothesis of panic
      disorder, but alternative interpretations of this finding are available and
      further study is needed.

PMID- 1391294
TI  - 31Phosphorus magnetic resonance spectroscopy of the temporal lobes in
      schizophrenia.
AB  - Eleven schizophrenic patients and nine normal controls were studied using in vivo
      31Phosphorous magnetic resonance spectroscopy (31P MRS) to test the hypothesis of
      metabolic asymmetry in the temporal lobes in schizophrenia. The controls did not
      demonstrate any asymmetry of phosphorous metabolite ratios, percentage of
      phosphorous metabolites, or pH. In the schizophrenics, however,
      phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) and
      phosphocreatine/inorganic phosphate (PCr/Pi) effects appeared to primarily
      reflect higher ratios on the right side, while the percentage of beta-ATP
      appeared to primarily reflect higher relative concentrations in the left temporal
      lobe. Moreover, significant negative correlations were noted between total Brief
      Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left
      temporal lobes. These results support the hypothesis of an asymmetric
      distribution of 31P metabolites in the temporal lobe of schizophrenic patients,
      and also show an association between temporal lobe phosphorous metabolism and the
      severity of psychiatric symptomatology.

PMID- 1391295
TI  - Abnormal cerebral laterality in bipolar depression: convergence of behavioral and
      brain event-related potential findings.
AB  - Cerebral laterality in bipolar and unipolar major depression was compared using
      visual half-field and dichotic listening measures of perceptual asymmetry. The
      results replicate our prior finding of abnormal laterality in bipolar depressed
      patients on a visuospatial test. Bipolar patients (n = 11) failed to show the
      left visual field (right hemisphere) advantage for dot enumeration seen for both
      unipolar patients (n = 43) and normal controls (n = 24). Bipolar patients
      performed significantly poorer than unipolar patients on normal controls for left
      visual field, but not right visual field stimuli. An electrophysiological
      correlate of abnormal visual field asymmetry in bipolar depression was found in
      brain event-related potentials recorded during audiospatial and temporal
      discrimination tasks. Bipolar patients had smaller N100 amplitudes for test
      stimuli in the left than right hemifield, whereas unipolar patients and normals
      did not. The origins of left hemifield deficits in bipolar depression are
      discussed in terms of right-sided dysfunction of an arousal/attentional system
      involving temporoparietal and possibly frontal regions.

PMID- 1391296
TI  - Mental and physical state in subclinical hyperthyroidism: investigations in a
      normal working population.
AB  - We investigated whether subclinically hyperthyroid individuals selected from a
      nonpatient working population exhibit similar impairments to those found in
      studies with patients. Sixteen subclinically hyperthyroid subjects without
      apparent reason (SH-0) and 15 subclinically hyperthyroid subjects on
      levothyroxine (SH-T4) were compared with 27 euthyroid controls with respect to
      signs and symptoms of hyperthyroidism, sleep, depressivity, ability to
      concentrate, anxiety, and other dimensions of well-being. We found that SH-T4
      exhibited significantly higher TT4 levels, TT4/TBG ratios, and more palpitations
      than controls. Furthermore, they slept less. The SH-0 subjects reported being in
      a better mood and less touchy than controls. Psychometric results of all groups
      were within the normal range. A comparison of this study to previous studies
      reveals that TT4 levels or TT4/TBG ratios may play a crucial role in the
      development of the predominantly nervous symptoms in subclinical hyperthyroidism.
      Possible reasons for the discrepancies between results in hospital and
      nonhospital settings are discussed.

PMID- 1391297
TI  - Cholinergic REM sleep induction test in subjects at high risk for psychiatric
      disorders.
AB  - The influence of the cholinergic agonist RS 86 on electroencephalographic (EEG)
      sleep was investigated in 21 healthy members of families identified as being at
      high risk for psychiatric disorders and in 17 healthy control subjects without
      any personal or family history of a psychiatric illness. In comparison to the
      placebo night, the administration of RS 86 led to a shortening of rapid eye
      movement (REM) latency in both groups. This effect, however, was much more
      pronounced in the high-risk group, whereas in the control subjects the arousal
      system and the slow-wave sleep during the first nonREM period were more affected.
      These observations suggest that the cholinergic action on sleep regulating
      mechanisms has differing preferential targets in high-risk probands and in
      control subjects.

PMID- 1391298
TI  - Increased CSF HVA with craving in long-term abstinent cocaine abusers.

PMID- 1391299
TI  - Uterine secretion of prostaglandin F2 alpha in response to oxytocin in ewes:
      changes during the estrous cycle and early pregnancy.
AB  - Experiment 1 was conducted to determine when the ovine uterus develops the
      ability to secrete prostaglandin F2 alpha (PGF2 alpha) in response to oxytocin
      and how development is affected by pregnancy. Pregnant and nonpregnant ewes
      received an injection of oxytocin (10 IU, i.v.) on Day 10, 13, or 16 postestrus.
      Jugular venous blood samples were collected for 2 h after injection for
      quantification of 13,14-dihydro-15-keto-PGF2 alpha (PGFM). In nonpregnant ewes,
      concentrations of PGFM increased following oxytocin on Day 16 but not on Day 10
      or 13. Concentrations of PGFM did not increase following treatment on Day 10, 13,
      or 16 in pregnant ewes. Therefore, the ability of oxytocin to induce uterine
      secretion of PGF2 alpha develops after Day 13 in nonpregnant but not in pregnant
      ewes. Experiment 2 was conducted to precisely define when uterine secretory
      responsiveness to oxytocin develops. Pregnant and nonpregnant ewes received
      oxytocin on Day 12, 13, 14, or 15. In nonpregnant ewes, concentrations of PGFM
      increased following treatment on Days 14 and 15, but not earlier. Peripheral
      concentrations of progesterone showed that uterine secretory responsiveness to
      oxytocin developed prior to the onset of luteal regression. As in experiment 1,
      the increase in concentrations of PGFM following administration of oxytocin was
      much lower in pregnant than in nonpregnant ewes; however, some pregnant ewes did
      respond to oxytocin with an increase in PGFM. In experiment 3, pregnant ewes
      received an injection of oxytocin on Day 18, 24, or 30 postmating. Concentrations
      of PGFM increased following oxytocin on Days 18 and 24. The conceptus appears to
      delay and attenuate the development of uterine secretory responsiveness to
      oxytocin.

PMID- 1391300
TI  - Expression of testicular messenger ribonucleic acid for luteinizing hormone
      receptor in the rat: developmental regulation of multiple transcripts during
      postnatal life.
AB  - On the basis of earlier observations of changing testicular LH receptor levels
      during postnatal development of the rat, we analyzed the levels of LH receptor
      mRNA transcripts in testes of rats at ages 5-70 days. Extracted testis RNA,
      prepared for Northern blotting, was hybridized with a specific LH receptor cRNA
      probe derived from subcloned cDNA corresponding to the extracellular domain of
      the receptor. Six LH receptor mRNA transcripts with molecular sizes of 7.8, 7.0,
      4.2, 2.5, 1.8, and 1.2 kb were identified. Of these, the 1.2- and the 1.8-kb mRNA
      transcripts presumably code for truncated forms of LH receptor. At 5 days, only
      the 1.8- and the 4.2-kb mRNA transcripts were observed. Additional 7.0- and 1.2
      kb transcripts appeared at 10 and 15 days, respectively. From the age of 25 days
      through adulthood, all six mRNA transcripts were observed. Densitometric analyses
      revealed that the amounts of the 7.0- and 1.8-kb mRNA transcripts correlated well
      with LH receptor levels, while the 4.2-kb transcript showed high levels earlier
      in life with poor correlation to LH receptor number. Because the 1.8 kb receptor
      transcript lacked transmembrane domains, the present results suggest the 7.0-kb
      LH receptor transcript as the likely candidate to encode the functional receptor.
      These data provide the basis for future analyses of the molecular regulation of
      LH receptor expression.

PMID- 1391301
TI  - Differential response to gonadotropins and prostaglandin E2 in ovarian tissue
      during prenatal and postnatal development in cattle.
AB  - In cattle, growing follicles are present in fetal ovaries during the last part of
      gestation. This study examines the extent of changes in basal and hormone
      stimulated adenylyl cyclase (AC) activity in ovaries of the bovine fetus when the
      first follicles begin to grow. The first growing follicles appeared in fetal
      ovaries around Day 180 and consisted mainly of primary and secondary follicles;
      few antral follicles were present before Day 220 of gestation. Basal AC activity
      in ovarian membranes increased simultaneously with the beginning of follicle
      growth in the fetus (5.8 +/- 0.9 vs. 9.3 +/- 1.3 pmol cAMP/mg protein/min at 130
      180 and 180-210 days of gestation, respectively p less than 0.05). During the
      same time period, there was a significant increase in both the absolute (16.1 +/-
      1.2 to 39.9 +/- 1.4 pmol cAMP/mg protein/min) and the relative (2.8 +/- 0.1 to
      4.3 +/- 0.3 times the basal level, p less than 0.05) effects of guanosine
      triphosphate (GTP). After birth, basal and GTP-stimulated AC activities (pmol
      cAMP/mg protein/min) increased markedly in ovarian membranes of 1-wk-old calves
      and then decreased with age; the lowest levels were measured in mature cyclic
      cows. However, the relative effect of GTP (times the basal level) did not show
      this age-related variation. Prostaglandin E2 (PGE2) stimulation of AC in ovarian
      membranes from fetuses was high even on Day 120 (2.1 +/- 0.3 times the control
      level).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391302
TI  - High survival of rabbit morulae after vitrification in an ethylene glycol-based
      solution by a simple method.
AB  - Rabbit morulae were exposed to a vitrification solution-modified PBS [PB1] medium
      containing 40% ethylene glycol + 18% Ficoll + 0.3 M sucrose (EFS) for 2, 5, or 10
      min at 20 degrees C and were vitrified in liquid nitrogen. When morulae were
      rapidly warmed, 96% had an intact zona pellucida. When embryos were cultured
      after removal of the mucin coat, high proportions of them formed blastocoel (79
      100%), but the percentage of embryos developed to fully expanded blastocysts
      decreased with increased exposure time 87%, 40%, and 17%). The survival rate of
      morulae vitrified after removal of the mucin coat was lower than that of mucin
      intact embryos. To assess the development potential in vivo, 131 embryos were
      vitrified after 2 min of exposure to EFS solution; all the embryos were recovered
      and 120 were transferred to recipients without removal of the mucin coat,
      resulting in 78 (65%) full-term fetuses or young. This simple method, which
      yields high survival both in vitro and in vivo, will be of practical use for
      vitrifying rabbit embryos.

PMID- 1391303
TI  - Correlation of sperm viability with gamete interaction and fertilization in vitro
      in the cheetah (Acinonyx jubatus).
AB  - Sperm-oocyte interaction in vitro was studied in the cheetah, a species known to
      produce poor quality ejaculates and to experience low rates of fertility. Twelve
      female cheetahs were injected (i.m.) with eCG followed by hCG 84 h later. Twenty
      four to 26 h post hCG, each was subjected to laparoscopic oocyte aspiration. A
      sperm motility index (SMI) was calculated for each of 9 cheetah sperm donors that
      produced ejaculates averaging 41.3 +/- 22.9 x 10(6) motile sperm and 28.4 +/-
      4.9% structurally normal sperm. Each ejaculate was used to inseminate cheetah
      oocytes from 1 or 2 females and salt-stored, domestic cat oocytes. The presence
      of ovarian follicles (greater than or equal to 1.5 mm in diameter) showed that
      all females responded to exogenous gonadotropins (range, 11-35 follicles/female).
      A total of 277 cheetah oocytes was collected from 292 follicles (94.9% recovery;
      23.1 +/- 2.2 oocytes/female). Of these, 250 (90.3%) qualified as mature and 27
      (9.7%) as degenerate. Of the 214 mature oocytes inseminated, 56 (26.2%) were
      fertilized, and 37 (17.3%) cleaved to the 2-cell stage in vitro; but the
      incidence of in vitro fertilization (IVF) varied from 0 to 73.3% (p less than
      0.001) among individual males. When oocytes from individual cheetahs (n = 5) were
      separated into two groups and inseminated with sperm from a male with an SMI
      greater than 0 after 6 h coincubation versus an SMI = 0 at this time, the mean
      fertilization rates were 28/44 (63.6%) and 0/37 (0%), respectively (p less than
      0.05). Of the 117 domestic cat oocytes coincubated with cheetah sperm, 96.6%
      contained 1 or more cheetah sperm in the outer half of the zona pellucida (ZP).
      Although the mean number of cheetah sperm penetrating the outer ZP of the cat
      oocyte was similar (p greater than 0.05) among all males, there was a positive
      correlation between the number of sperm reaching the inner half of the ZP and
      fertilization rate in vitro (r = 0.82; p less than 0.05). Compared to IVF
      efficiency in the domestic cat and tiger as reported in earlier studies, IVF
      efficiency in the cheetah is low. Because oocytes from 11 of 12 cheetahs were
      fertilized in vitro, there is no evidence that the female gamete is incompetent.
      Although sperm pleiomorphisms may contribute to poor reproductive performance,
      examination of the data on the basis of individual sperm donors reveals that
      effective gamete interaction in the cheetah is dictated, in part, by sperm
      motility.

PMID- 1391304
TI  - Uterine epithelial cells synthesize granulocyte-macrophage colony-stimulating
      factor and interleukin-6 in pregnant and nonpregnant mice.
AB  - Cytokine secretion by endometrial cells from estrous and mated mice was measured
      using specific bioassays. The granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and interleukin-6 (IL-6) contents of uterine intraluminal fluid were
      elevated greater than 20-fold and 250-fold respectively following mating, and
      both cytokines were synthesized in abundance in vitro by uterine cells harvested
      at estrus and on Day 1 of pregnancy. Synthesis was not impaired in genetically
      lymphocyte-deficient nude, SCID, or beige mice. To determine the cellular origin
      of the cytokines, a panning technique employing monoclonal antibodies against a
      range of leukocyte and other lineage markers was used to isolate uterine cell
      subsets in vitro. These experiments identified glandular and/or luminal
      epithelial cells as the major source of GM-CSF and IL-6 in estrous and pregnant
      uteri. Stromal fibroblasts also synthesized IL-6, as did macrophages in mated
      mice. Epithelial cells harvested from midgestation uteri secreted GM-CSF and IL-6
      in quantities similar to those of cells from estrous and mated mice.
      Bioactivities of both cytokines derived from epithelial cells were neutralized by
      specific antibodies, and size-exclusion chromatography of conditioned media from
      uterine cells revealed peaks of GM-CSF and IL-6 bioactivity with M(r) 23,000 and
      23,000-26,000, respectively. Bioassay of luminal fluids and culture supernatants
      were negative for the cytokines interleukin-1, interleukin-2, interleukin-3, and
      tumor necrosis factor-alpha. These studies identify murine uterine epithelium as
      a potent source of the cytokines GM-CSF and IL-6, which we postulate have
      potentially important functions in pregnancy through actions on target cells in
      both the uterus and the conceptus.

PMID- 1391305
TI  - Early postnatal androgenization imprints selective changes in the action of
      estrogens in the rat uterus.
AB  - Exposure of animals perinatally to some hormonally active agents may imprint
      permanent changes on the action of related hormones. The present study
      investigated the effects of early postnatal androgenization on various genomic
      responses to estrogen in the uterus of prepubertal rats. Female rats were
      androgenized at postnatal ages of 1, 5, or 13 days with a single s.c. injection
      of testosterone propionate. At the age of 21 days, the animals were stimulated
      with estrogens. The uteri of androgenized and control rats were analyzed
      morphometrically to measure genomic parameters of estrogen stimulation in the
      uterus. The results demonstrate that early postnatal androgenization does not
      equally affect all uterine cell types and that the effects of androgenization
      change according to the age at androgenization. The dissociation between the
      various responses according to the time of androgenization suggests that there
      are critical ages at which the uterine cell types that respond to estrogens can
      be altered permanently by imprinting. The finding of changes in the action of
      estrogen induced by androgenization at older than neonatal ages in the rat
      suggests that similar changes may occur in humans exposed to androgens during
      their extrauterine life. This result also points to the need for further studies
      using the rhesus monkey because of its close resemblance to the human with
      respect to female reproductive physiology.

PMID- 1391306
TI  - Freeze-induced membrane damage in ram spermatozoa is manifested after thawing:
      observations with experimental cryomicroscopy.
AB  - Cryoinjury in ram sperm was investigated by direct observation, using
      cryomicroscopy, to validate model hypotheses of freezing injury in such a
      specialized cell. Fluorescein diacetate was used to determine when during the
      freeze-thaw cycle the sperm membrane became permeable. In noncryoprotected sperm
      plasma membrane, integrity was maintained throughout the cooling and freezing
      process, but fluorescein leakage occurred during rewarming. The temperature of
      post-thaw permeabilization varied in relation to the minimum temperature reached
      during freezing; cells cooled to -10 degrees C retained fluorescence into the
      post-thaw temperature range of 9-24 degrees C (mean +/- SEM; 13.25 +/- 0.91
      degrees C), whereas cells cooled to -20 degrees C lost fluorescence shortly after
      thawing (mean +/- SEM; 2.62 +/- 0.91 degrees C). Sperm cooled to 5 degrees C, but
      not frozen, retained fluorescence during rewarming up to 20-30 degrees C. The
      inclusion of glycerol and egg yolk in the freezing medium significantly and
      independently increased the post-thaw permeabilization temperature. Maintenance
      of fluorescence was also correlated with ability to resume motility after
      thawing. Sperm reactivation experiments were undertaken to examine deleterious
      effects of freezing upon the flagellar microtubular assembly. No direct evidence
      for such effects was obtained. Instead, a highly significant correlation between
      minimum freezing temperature and post-thaw temperature of initial reactivation
      was detected.

PMID- 1391307
TI  - Differential temporal and spatial expression of mRNA encoding extracellular
      matrix components in decidua during the peri-implantation period.
AB  - Changes in the temporal and spatial patterns of expression of mRNA encoding
      uterine extracellular matrix (ECM) proteins were determined during the peri
      implantation period. Northern blot hybridization of cDNAs corresponding to
      laminin (LM) B1, LM B2, entactin, fibronectin, collagen (CL) type IV alpha 1, and
      CL IV alpha 2 was performed on RNA extracted from either whole mouse uteri or
      endometrial explants between Day 4, i.e., the day of implantation, and Day 7 of
      pregnancy, when the decidual response is well established. These analyses
      revealed a dramatic increase in LM B2, CL IV alpha 1, and CL IV alpha 2 mRNA
      expression by Day 7 of pregnancy. Relative levels of the mRNA encoding other ECM
      components, including LM B1, were not altered when compared to changes in the
      relative level of expression of glyceraldehyde-3-phosphate dehydrogenase mRNA.
      The differential expression of the B chains of LM appeared to be limited to the
      stromal cells of the endometrium. In situ hybridization of uterine sections with
      cRNA probes corresponding to LM B1, LM B2, and CL IV alpha 1 demonstrated that LM
      B1 was expressed temporally in high amounts in the primary decidual zones (PDZ)
      and persisted throughout PDZ degeneration. LM B2 mRNA was expressed in both
      primary and secondary decidual zones and persisted through Day 8 of pregnancy. CL
      IV alpha 1 mRNA expression mimicked that of LM B2. Oviduct ligation on Day 2 of
      pregnancy was used to prevent embryo transport to one uterine horn, whereas
      decidualization and embryo implantation were permitted in the contralateral horn.
      This experiment demonstrated that the increases in uterine ECM mRNA expression
      were not due solely to the changing hormonal milieu of the uterus. ECM
      components, including CL IV, have been shown to bind growth factors such as
      transforming growth factor-beta (TGF-beta) in an insoluble but biologically
      active form. The remarkable similarity between the pattern of CL IV and LM B2
      expression and previously reported TGF-beta deposition (Tamada et al., Mol
      Endocrinol 1990; 4:965-972) prompted examination of the effects of this growth
      factor on blastocyst development in vitro. TGF-beta 1 was tested for its ability
      to alter embryo outgrowth on LM-coated tissue culture surfaces; however,
      significant differences in the rate or extent of outgrowth in the presence of TGF
      beta were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391308
TI  - Splenic macrophages enhance prolactin-induced progestin secretion from mature rat
      granulosa cells in vitro.
AB  - The effect of splenic macrophages on in vitro progestin secretion (the sum of the
      progesterone and 4-pregnen-20 alpha-ol-3-one concentrations in the medium) from
      mature rat granulosa cells was examined by means of co-culture techniques. When
      splenic macrophages (3.0 x 10(5) cells/ml) obtained from adult female rats on the
      evening of proestrus (1800 h) were added to granulosa cells (1.5 x 10(5)
      cells/ml) and co-cultured for 96 h in the absence of prolactin (PRL), progestin
      secretion from granulosa cells did not change. However, co-culture of granulosa
      cells with the macrophages in the presence of PRL (2 micrograms/ml) significantly
      enhanced progestin secretion after 48 h of culture. This stimulatory effect on
      progestin secretion was observed only when the number of macrophages added was
      more than twice the number of granulosa cells. On the other hand, splenic
      macrophages obtained on the evening of diestrus had no effect on progestin
      secretion from granulosa cells even in the presence of PRL. These results suggest
      that splenic macrophages can enhance PRL action so as to stimulate progestin
      secretion from granulosa cells and that this function of splenic macrophages
      varies during the estrous cycle.

PMID- 1391309
TI  - The effect of testosterone on serum gonadotropins of castrated rats kept under
      different lighting conditions.
AB  - Testosterone feedback sensitivity was measured as the ability of testosterone
      propionate to decrease serum LH and FSH of long-term castrated (4 wk) rats under
      four different lighting conditions: periodic light (12L:12D), constant light
      (LL), constant darkness (DD), and dim night illumination (1 lx) with a 12L:12D
      photoperiod. Rats were exposed to the different lighting conditions for 1 wk,
      during which they received daily testosterone propionate (125 micrograms or 250
      micrograms s.c.). At the end of the experiment the rats were decapitated at 1100
      h, and serum gonadotropin levels were measured by RIA. Serum LH of the rats kept
      under LL was reduced to the level of the intact rats with the smaller
      testosterone dose (125 micrograms/day). Under all other lighting conditions only
      the large dose (250 micrograms/day) was able to restore the serum LH
      concentration to the level of the intact rats. Serum FSH was restored only
      partially, and the effect was the same with both doses and similar under all
      lighting conditions. We conclude that the increase in testosterone negative
      feedback sensitivity was not caused by the lack of periodicity of illumination
      alone, but that sufficient intensity of lighting throughout the 24 h was needed
      as well.

PMID- 1391310
TI  - Seasonal changes of gonadotropin-releasing hormone secretion in the ewe.
AB  - A sustained volley of high-frequency pulses of GnRH secretion is a fundamental
      step in the sequence of neuroendocrine events leading to ovulation during the
      breeding season of sheep. In the present study, the pattern of GnRH secretion
      into pituitary portal blood was examined in ewes during both the breeding and
      anestrous seasons, with a focus on determining whether the absence of ovulation
      during the nonbreeding season is associated with the lack of a sustained increase
      in pulsatile GnRH release. During the breeding season, separate groups (n = 5) of
      ovary-intact ewes were sampled during the midluteal phase of the estrous cycle
      and following the withdrawal of progesterone (removal of progesterone implants)
      to synchronize onset of the follicular phase. During the nonbreeding season,
      another two groups (n = 5) were sampled either in the absence of hormonal
      treatments or following withdrawal of progesterone. Pituitary portal and jugular
      blood for measurement of GnRH and LH, respectively, were sampled every 10 min for
      6 h during the breeding season or for 12 h in anestrus. During the breeding
      season, mean frequency of episodic GnRH release was 1.4 pulses/6 h in luteal
      phase ewes; frequency increased to 7.8 pulses/6 h during the follicular phase
      (following progesterone withdrawal). In marked contrast, GnRH pulse frequency was
      low (mean less than 1 pulse/6 h) in both groups of anestrous ewes (untreated and
      following progesterone withdrawal), but GnRH pulse amplitude exceeded that in
      both luteal and follicular phases of the estrous cycle.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391312
TI  - Luteinizing hormone requirements for ovulation in the rat.
AB  - Luteinizing hormone requirements for ovulation induction were studied in
      proestrous rats through detailed observation of the preovulatory surge, through
      various forms of LH injection under sodium pentobarbital blockade, and through
      estimation of LH uptake by the ovary. Blood LH levels in individual proestrous
      rats were obtained every 30 min and grouped according to their peak time
      (designated 0 h); mean LH levels higher than 7 and 5 ng/ml continued for 30 min
      and 2.5 h, respectively, the pituitary LH contents at 1400 and 2000 h on the day
      of proestrus were 2.1 and 0.7 micrograms, respectively, indicating that the
      amount of LH secreted during the surge was at least 1.4 micrograms. Single
      intravenous injections of 2 micrograms and 1 micrograms of pure rat LH (NIDDK-rLH
      I-7; FSH and prolactin contaminations: 0.02% and less than 0.01%, respectively)
      to sodium pentobarbital-blocked rats induced ovulation in 4 out of 4 rats and 4
      out of 6 rats, respectively, while 500 ng failed to induce ovulation in any (out
      of 7) rats. Two injections of 300 ng each with an interval of 20 min induced
      ovulation in 3 out of 8 rats, but if the interval was prolonged to between 30 and
      120 min, 100% ovulation was obtained. Blood LH levels in these experiments
      indicated that a lower long-lasting LH level (about 5 ng/ml blood) is more
      important than a short, high level for ovulation induction. It was also shown
      that this level of LH could be given in separate doses if the interval was 30-120
      min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391311
TI  - Loss of collagen type VI from rat endometrial stroma during decidualization.
AB  - The expression of collagen type VI in the extracellular matrix of rat uterine
      endometrial stroma after a decidual stimulus was examined by immunolocalization
      and immunoblotting. The intermediate filament protein, desmin, was used as a
      marker to identify decidual cells. Tissue was examined from pregnant animals and
      from ovariectomized, hormone-treated rats in which decidualization had been
      induced artificially. In undifferentiated tissue from both groups of animals,
      collagen type VI was abundant, and desmin was present only in vascular smooth
      muscle cells. By 72 h after a decidual stimulus, however, collagen type VI had
      essentially disappeared from the matrix of the antimesometrial stromal
      compartment, and desmin was highly expressed in the decidualizing cells. During
      regression of the decidual tissue, collagen type VI began to reappear in the
      stromal matrix, whereas desmin expression declined as decidual cells degenerated.
      These results indicate that remodeling of the uterine extracellular matrix in
      response to embryo implantation is a function of the differentiating decidual
      cell.

PMID- 1391313
TI  - Central actions of neuropeptide-Y may provide a neuromodulatory link between
      nutrition and reproduction.
AB  - Central injection of neuropeptide-Y (NPY) has been shown to attenuate secretion
      of LH in ovariectomized rats, rabbits, and monkeys. Several investigators have
      reported elevated concentrations of NPY in the central nervous system of
      undernourished animals. The relationship between nutrition and reproduction
      positions NPY as a potential neuromodulator involved in nutritionally induced
      changes in secretion of LH. Three experiments were conducted with the following
      objectives: 1) to examine the effects of NPY on secretion of LH in ovariectomized
      (OVX) ewes and the influence of estradiol-17 beta (E) on these effects; 2) to
      determine whether NPY may act through direct effects on the pituitary to
      influence secretion of LH; and 3) to determine changes in concentrations of NPY
      in laterocerebro-spinal fluid (CSF) of food-restricted ewes compared to well-fed
      ewes. In Experiment 1, OVX ewes with s.c. implants of E (OVX + E, n = 4) or no
      steroid treatment (OVX, n = 4) were fitted with intracerebroventricular (i.c.v.)
      and jugular cannulae. One of 4 doses of porcine NPY (pNPY; 0, 0.5, 5, or 50
      micrograms) was injected i.c.v. and blood samples were collected every 10 min for
      4 h prior to and following i.c.v. injection. Blood serum was assayed for LH. The
      experiment was replicated four times such that each ewe received each dose of
      pNPY. Mean concentrations of LH as well as frequency and amplitude of pulses of
      LH were attenuated in response to i.c.v. injection of pNPY in a dose-related
      manner in both OVX and OVX + E ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391314
TI  - Different patterns of myometrial activity and 24-h rhythms in myometrial
      contractility in the gravid baboon during the second half of pregnancy.
AB  - Two clearly distinct epochs of myometrial contractility were observed in 13
      pregnant baboons when recorded either as intraamniotic pressure (IAP) or
      myometrial electromyogram (EMG). Contractures, epochs lasting longer than 3 min,
      were the characteristic form of myometrial activity throughout pregnancy.
      Contractures generated only small increases in IAP. Short-lived contractions,
      generating larger increases in IAP, were characteristic of labor and delivery.
      Power spectral analysis of IAP and myometrial EMG activity proved to be an
      effective means whereby periods when the myometrium was in the contractures or
      contractions mode could be easily distinguished. Concomitantly recorded maternal
      intraabdominal temperature showed significant 24-h variations. When myometrial
      activity switched from low-amplitude, long-lasting regular contractures of
      pregnancy to contractions, the switch always occurred around the onset of
      darkness. Five baboons went into spontaneous labor, 3 prematurely and 2 at term.
      In these animals the switch from contractures to contractions occurred for
      several nights before delivery. The recurrence and timing of the switch from
      contractures to contractions for several nights before delivery were similar to
      the pattern we and others have observed in the pregnant rhesus monkey. The
      presence of 24-h periodicity in the patterns of specific types of myometrial
      activity in another nonhuman primate lends support to the view that similar 24-h
      patterns of myometrial activity may occur in pregnant women.

PMID- 1391315
TI  - Effects of topical and systemic estrogen on morphology of porcine uterine luminal
      epithelia.
AB  - Silastic beads containing either estradiol-17 beta or cholesterol were surgically
      introduced into the uterine lumina of gifts on Day 10 postestrus, and the animals
      were killed on Day 13 or 19 (n = 4/day/treatment). An additional group of gifts
      were injected i.m. with 5 mg estradiol valerate on Days 11-15 of the estrous
      cycle and were killed on Day 13 and Day 19 (n = 4/day). Endometrial samples were
      collected and prepared for light and electron microscopic study. Cholesterol
      beads did not appear to affect endometrial structure. Both intrauterine and
      systemic treatment of gilts with estradiol induced folding along the mesometrial
      region of the uterus similar to that which occurs during early pregnancy. The
      uterine luminal epithelium of animals exposed to both exogenous hormone
      treatments exhibited morphological features similar to those of this layer during
      early pregnancy: evidence of increased synthetic and secretory activity,
      decreased incidence of cell degeneration, accumulation of glycogen and dense
      inclusions, variation in nuclear position, and elaboration of a thick fibrous
      glycocalyx.

PMID- 1391316
TI  - In vivo treatment with interferon-gamma during early pregnancy in mice induces
      strong expression of major histocompatibility complex class I and II molecules in
      uterus and decidua but not in extra-embryonic tissues.
AB  - Allopregnant (NFR/N [Swiss-derived] H-2q females x 57/Bl H-2b males) and
      syngeneically pregnant (NFR/N x NFR/N) mice were subjected to daily injections
      (10(5) U/mouse/day, from Day 5.5 of gestation) of recombinant rat or mouse
      interferon-gamma (IFNg) in order to investigate its ability to induce extra
      embryonic major histocompatibility complex (MHC) expression and antipaternal
      immune reactions if administered during the first part of the gestation period.
      In addition, a limited number of IFNg-treated embryo-transferred NFR/N mice
      carrying C57/B1 embryos (representing a complete allogenic pregnancy) were
      investigated. Mouse and rat IFNg caused the same type of histological and
      physiological changes, and most of the experiments were performed by using rat
      IFNg. Several IFNg-treated mice (irrespective of type of mating) showed a drop in
      weight and a high rate of resorptions at Day 12.5 of gestation. This interference
      with pregnancy appeared not to be caused by immunological reactions against the
      feto-placental unit (no leukocyte infiltration and no significant effect on serum
      levels of antipaternal antibodies in preimmunized allopregnant IFNg-treated
      mice). Immunohistochemical stainings of cryosectioned tissues at Day 9.5 of
      pregnancy revealed that IFNg treatment caused a strong induction of MHC class I
      and class II expression on most cells in the uterus and on several cells in the
      maternal decidua, while there was a complete absence of detectable MHC class I
      and class II expression in the extra-embryonic tissues. Characteristic for a Day
      12.5 placenta of an IFNg-treated mouse (including embryo-transferred mice) was a
      strongly MHC class II-induced maternal decidua and a completely MHC class II
      negative fetal placenta. The pattern of IFN-induced MHC class I expression was
      similar to that of class II, with the exception of class I expression on
      scattered cells within the basal zone. Thus, the present study provides
      immunohistological evidence that IFNg administered in vivo during the first part
      of gestation is not capable of inducing MHC expression on murine extra-embryonic
      cells despite an extremely high expression of MHC molecules on decidual cells in
      intimate contact with extra-embryonic tissues. It is likely that the resistance
      to IFNg-mediated induction of MHC expression on extra-embryonic cells is of basic
      importance for the protection of mammalian semi-allogeneic fetuses.

PMID- 1391317
TI  - Fertilization failure of frozen mouse oocytes is not due to premature cortical
      granule release.
AB  - The proportion of mouse oocytes that were fertilized in vitro after storage at 
      196 degrees C in the presence of 1.5 M dimethylsulfoxide (DMSO) was significantly
      lower than in unfrozen controls (39% vs. 81%). Sperm failed to penetrate the zona
      pellucida of approximately 80% of the frozen oocytes that remained unfertilized.
      Removal of the zona restored fertilization to control levels, indicating that
      changes induced in the zona during freezing and/or thawing were the primary cause
      of fertilization failure. Sperm-oocyte fusion, sperm nucleus decondensation, and
      the resumption of meiosis in frozen oocytes appeared to be delayed but
      subsequently fertilization progressed normally. No evidence was found to suggest
      zona modification by the premature release of fucosyl-rich glycoconjugates of
      cortical granule origin onto the surface of the plasma membrane of frozen oocytes
      stained immediately after thawing with fluorescently labeled Ulex europaeus
      lectin. Only a few frozen (less than 5%) and control (less than 3%) oocytes that
      failed to fertilize in vitro had fucosylated molecules on the plasma membrane.
      Prolonged exposure of fertilized oocytes to DMSO at 4 degrees C did not alter the
      pattern of lectin binding. In conclusion, fertilization is inhibited in frozen
      thawed oocytes by as yet undefined modifications to the zona pellucida which do
      not involve the premature release of cortical granules.

PMID- 1391318
TI  - Mouse oocytes promote proliferation of granulosa cells from preantral and antral
      follicles in vitro.
AB  - Evidence is now emerging that the oocyte plays a role in the development and
      function of granulosa cells. This study focuses on the role of the oocyte in the
      proliferation of (1) undifferentiated granulosa cells from preantral follicles
      and (2) more differentiated mural granulosa cells and cumulus granulosa cells
      from antral follicles. Preantral follicles were isolated from 12-day-old mice,
      and mural granulosa cells and oocyte-cumulus complexes were obtained from
      gonadotropin-primed 22-day-old mice. Cell proliferation was quantified by
      autoradiographic determination of the 3H-thymidine labeling index. To determine
      the role of the oocyte in granulosa cell proliferation, oocyte-cumulus cell
      complexes and preantral follicles were oocytectomized (OOX), oocytectomy being a
      microsurgical procedure that removes the oocyte while retaining the three
      dimensional structure of the complex or follicle. Mural granulosa cells as well
      as intact and OOX complexes and follicles were cultured with or without FSH in
      unconditioned medium or oocyte-conditioned medium (1 oocyte/microliter of
      medium). Preantral follicles were cultured for 4 days, after which 3H-thymidine
      was added to each group for a further 24 h. Mural granulosa cells were cultured
      as monolayers for an equilibration period of 24 h and then treated for a 48-h
      period, with 3H-thymidine added for the last 24 h. Oocyte-cumulus cell complexes
      were incubated for 4 h and then 3H-thymidine was added to each group for an
      additional 3-h period. FSH and/or oocyte-conditioned medium caused an increase in
      the labeling index of mural granulosa cells in monolayer culture; however, no
      differences were found among treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391319
TI  - Bioactive and immunoreactive concentrations of circulating luteinizing hormone
      during sexual maturation in the bovine.
AB  - The characteristics of circulating LH during sexual maturation in cattle were
      assessed by examining bioactive and immunoreactive LH concentrations, as well as
      their ratio (B/I ratio). Male and female intact control (CONT), gonadectomized
      (GNX; at 241 +/- 3 days of age, Day 0 of the study), and gonadectomized animals
      administered 17 beta-estradiol (GNXE) were evaluated. Serum samples were
      collected at 15-min intervals for 24 h at 1, 7, 13, 17, 21, 25, 29, 33, 37, and
      43 wk subsequent to Day 0. Bioactive LH was assessed with an in vitro bioassay
      using mouse testicular interstitial cells. In initial experiments, immunoreactive
      LH was quantified in RIAs using three different antibodies. The two RIAs
      employing polyclonal antibodies overestimated low LH concentrations, but the
      absolute values obtained in each of the three assays were highly correlated.
      Hence, immunoreactive LH was measured in an RIA using monoclonal anti-bovine LH
      (bLH) (JR-518B7). No significant changes in the B/I ratios were observed during
      individual pulses of LH secretion. Accordingly, pools consisting of equal volumes
      of the serial blood samples collected during the 24-h period for each animal at
      each stage of maturation (pools) were compared. LH B/I ratios for GNX females
      increased significantly with time (p less than 0.01) and the B/I ratios for GNX
      males were significantly higher than for GNX females (p less than 0.05).
      Concentrations of LH in most of the pools for GNXE and CONT animals were
      extremely low or nondetectable until the later bleeding periods.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1391320
TI  - Immunoreactive inhibin in plasma, amniotic fluid, and gonadal tissue of male and
      female chick embryos.
AB  - Immunoreactive inhibin was measured in plasma, amniotic fluid, gonads, and
      Wolffian bodies (mesonephros) of male and female chick embryos during the last
      week of their 21-day incubation period. The antiserum used was raised against
      bovine 31-kDa inhibin and was validated for RIA of inhibin in the chicken.
      Amniotic fluid concentrations of immunoreactive inhibin were relatively low and
      remained constant between Days 14 and 19. Plasma concentrations, in contrast,
      were high on Day 14 but declined steeply thereafter. Significantly higher plasma
      concentrations were noted in male than in female embryos and an even more
      pronounced sex difference was observed for the gonadal inhibin content. On Day
      21, testes contained approximately 35 times more immunoreactive inhibin than
      ovaries. Surprisingly, inhibin contents in testes and male Wolffian bodies
      increased rather than decreased towards the end of the incubation period,
      indicating that gonadal and plasma inhibin concentrations are regulated, at least
      in part, independently. It is concluded that the chick embryo presents a
      convenient model for study of the secretion, the control, and the role of inhibin
      from fetal origin. The sex difference in plasma and gonadal inhibin suggests a
      differential role of inhibin in the development of the reproductive system of
      both sexes.

PMID- 1391321
TI  - Maturation of the hypothalamo-pituitary-gonadal axis of male Syrian hamsters.
AB  - Light-microscope immunocytochemistry (ICC) was used to investigate postnatal
      changes in the morphology of LHRH neurons in the brains of male Syrian hamsters
      and to relate these changes to more overt maturational developments within the
      hypothalamo-pituitary-gonadal axis. The animals were maintained under long-day
      photoperiods (14L:10D), and groups of 6-7 were killed at 10-day intervals from
      Day 15 to Day 65. Their brains were fixed with 4% paraformaldehyde, sectioned
      sagittally with a vibratome (75 microns), and processed for ICC using monoclonal
      LHRH antibody HU4H. Throughout the study period, the hamsters showed a
      progressive increase in plasma gonadotropin levels, closely followed by an
      increase in testicular weight and plasma testosterone levels. Histology of the
      testes revealed that spermatogenesis was already qualitatively completed by Day
      35 and quantitative aspects were established by Day 45. Within the brain, LHRH
      neuronal perikarya were distributed primarily in the medial septal-preoptic area
      and the diagonal band of Broca; morphologically, these immunopositive neurons
      were either monopolar or bipolar. The total number of LHRH neurons detected in
      the areas examined was approximately 440 throughout the developmental period, and
      the relative proportions of monopolar and bipolar subtypes (86% and 14%,
      respectively) remained unchanged. In contrast, the area of the perikarya, as
      determined by autoimage analysis, showed a highly significant age-related
      increase, both for the monopolar and bipolar neurons. It is suggested that these
      developmental changes in the LHRH neurons reflect an increase in LHRH synthesis
      and may, therefore, provide a neuroendocrine trigger for the onset of puberty.

PMID- 1391322
TI  - Unilateral ovariectomy increases loss of primordial follicles and is associated
      with increased metestrous concentration of follicle-stimulating hormone in old
      rats.
AB  - The primary objective of these studies was to determine whether unilateral
      ovariectomy (ULO) would affect rate of loss of primordial follicles. In
      experiment 1, retired breeder rats, unilaterally ovariectomized and maintained on
      the experiment for 90 days after surgery, had fewer (p less than 0.01) primordial
      follicles per ovary than sham-operated controls of the same age. The purpose of
      experiment 2 was to determine whether time after ULO or age of rats was the
      critical factor necessary for increased loss of primordial follicles found after
      ULO in experiment 1. It was found that age was more important than time: when ULO
      was performed at 30 days of age, the number of primordial follicles did not
      decrease in ULO rats compared to controls (p greater than 0.05) before 250 days
      of age. Concentrations of FSH during metestrus were not greater (p greater than
      0.05) in ULO rats than in controls until rats were 250 days old. There were also
      fewer (p less than 0.05) growing follicles per ovary in ULO than in sham-operated
      rats at 250 days of age. It is concluded that ULO can increase the loss of
      primordial follicles, but only in old rats (greater than or equal to 250 days of
      age).

PMID- 1391323
TI  - Induction of ovulation and oocyte maturation of amphibian (Rana dybowskii)
      ovarian follicles by protein kinase C activation in vitro.
AB  - We previously reported that protein kinase C (PKC) activation induced meiotic
      maturation (germinal vesicle breakdown, GVBD) of Rana dybowskii follicular
      oocytes cultured in vitro without hormone treatment. The experiments reported
      here were carried out to establish whether ovarian follicles ovulated in response
      to PKC activation during culture. A phorbol ester, 12-O-tetradecanoylphorbol-13
      acetate (TPA), was used for PKC activation. TPA addition (10 microM) to cultured
      ovarian fragments induced ovulation and maturation of the oocytes similar to that
      seen following addition of frog pituitary homogenate (FPH, 0.05 pituitary/ml) or
      progesterone (0.5 microgram/ml). Such changes were not observed when ovarian
      fragments were treated with inactive phorbol ester. The time course of TPA
      induced ovulation was similar to that produced by FPH-stimulated ovulation. Both
      TPA- and FPH-stimulated ovulation and maturation were blocked by treatment with
      cycloheximide, forskolin (an adenylate cyclase stimulator), and 1-(5
      isoquinolinylsulfonyl)-2-methyl-piperazine (H-7; a PKC inactivator). FPH
      treatment markedly increased progesterone levels in the medium during ovarian
      fragment culture whereas TPA treatment failed to elevate progesterone levels.
      Thus, TPA treatment mimics FPH and progesterone in inducing ovulation and meiotic
      maturation in cultured amphibian ovarian fragments. The data strongly suggest
      that PKC plays an important role in regulating ovulation as well as in modulating
      amphibian oocyte maturation during follicular differentiation.

PMID- 1391324
TI  - Pattern of gonadotropin-releasing hormone (GnRH)-like stimuli sufficient to
      induce follicular growth and ovulation in ewes passively immunized against GnRH.
AB  - The pattern of GnRH-like stimuli capable of inducing follicular growth,
      ovulation, and luteal function was evaluated in ewes passively immunized against
      GnRH. The estrous cycles of 30 regularly cyclic sheep were synchronized using
      vaginal pessaries impregnated with a synthetic progestogen. Animals were
      passively immunized against GnRH (groups 2-5, n = 6) or the carrier protein,
      keyhole limpet hemocyanin (KLH; group 1, n = 6), at the time of pessary removal
      (PR). Circhoral delivery of saline (groups 1, 2, and 5) or low amplitude GnRH
      agonist (des-Gly10 GnRH ethylamide [100 ng/hourly pulse]; groups 3 and 4) was
      initiated at PR and continued for 3 (groups 4 and 5) or 12 days (groups 1-3). In
      groups 4 and 5, the amplitude of the GnRH-like stimulus was increased to 800
      ng/hourly pulse (stimulus-shift) during the 24-h period beginning 72 h after PR.
      The amplitude of the hourly stimulus was adjusted to 100 ng/pulse 96 h after PR
      and continued at that level to Day 12. The endocrine changes associated with
      follicle growth and maturation (serum concentrations of estradiol [E2] above 10
      pg/ml), ovulation (surge-like secretion of LH and FSH), and normal luteal
      function (serum concentrations of progesterone [P] above 2 ng/ml) were evident in
      ewes passively immunized against KLH (group 1). In this group, the preovulatory
      surge of gonadotropins was noted 48.7 +/- 1.2 h after PR. These endocrine events
      were blocked by passive immunization against GnRH (group 2).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1391325
TI  - Molecular genetics of sex determination in channel catfish: studies on SRY, ZFY,
      Bkm, and human telomeric repeats.
AB  - In amniotes, the banded krait minor (Bkm) minisatellite (GATA), the human
      telometric sequence (TTAGGG)7, and the Y-specific genes, ZFY and SRY, are
      associated with a particular sex. These sequences were studied in the channel
      catfish, Ictalurus punctatus. However, none was sex-specific in catfish; homologs
      of each were present in males and females. Our data suggest that components of
      mammalian sex-determining systems may be widespread and shared among the
      vertebrates in general. Whether those components are involved in sex
      determination in lower vertebrates or merely represent evolutionary precursors of
      sex-determining factors in amniotes remains to be determined.

PMID- 1391326
TI  - Evidence that platelet-activating factor suppresses uterine oxytocin-induced
      13,14-dihydro-15-keto-prostaglandin F2 alpha release and phosphatidylinositol
      hydrolysis in the ewe.
AB  - This study was conducted to determine whether platelet-activating factor (PAF)
      (1) attenuated oxytocin-induced secretion of the prostaglandin (PG) F2 alpha
      metabolite, PGFM, by the ovine uterus in situ and (2) inhibited the generation of
      the inositol phosphate secondary messengers by endometrial tissue in response to
      oxytocin challenge in vitro. Ovariectomized ewes received steroid replacement to
      mimic the luteal phase. Six ewes received intrauterine injections of 200
      micrograms PAF/uterine horn/day on Days 11-15, and 6 ewes were treated with
      vehicle. All ewes received 1 microgram oxytocin i.v. on Days 13-16. Pretreatment
      of ewes with PAF significantly suppressed PGFM release in response to oxytocin on
      Days 14 and 15 (p less than 0.005) compared to vehicle-treated ewes. PAF was not
      administered on Day 16, and the PGFM response to oxytocin was not different
      between groups. In a second experiment, ewes were given intrauterine injections
      of 200 micrograms PAF/uterine horn/day (n = 8) or vehicle (n = 7) on Days 11-15,
      and all ewes received 1 microgram oxytocin i.v. on Days 13 and 14. On Day 15 the
      uterus was removed, and the incorporation of 3H-inositol into inositol phosphates
      was determined in caruncular endometrium. Treatment of ewes with PAF in vivo
      reduced inositol monophosphate (IP1) generated by oxytocin (10(-6) M) by 56.4%,
      compared to that in endometrium from vehicle-treated controls, and also inhibited
      the incorporation of 3H-inositol into glycerophosphoinositol (GPI). If PAF was
      added to the endometrium during the incubation in vitro, the attenuation of
      inositol phosphate generation did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391327
TI  - Human placenta constitutively produces interleukin-8 during pregnancy and
      enhances its production in intrauterine infection.
AB  - Interleukin-8 (IL-8) exerts unique chemotactic and activating activity on
      neutrophils. To address the significance of IL-8 in the fetoplacental unit during
      pregnancy, we cultured human placental explants that had been obtained by vaginal
      delivery, Caesarean section, or artificial abortion and then measured the IL-8
      titer in the culture supernatants by enzyme immunoassay (EIA). Chorionic tissue
      from the first trimester produced a significant amount of IL-8 (2.2 +/- 0.4
      ng/ml/10 mg, n = 5), while placentae in the second trimester (8.3 +/- 1.6
      ng/ml/10 mg, n = 7) or at term (9.2 +/- 0.7 ng/ml/10 mg, n = 29) produced
      significantly higher amounts of IL-8. The presence or absence of labor did not
      affect the amount of placental IL-8 production. However, placentae with
      chorioamnionitis (25.2 +/- 1.6 ng/ml/10 mg, n = 9) showed significantly higher IL
      8 production than those without chorioamnionitis (p less than 0.0001). Northern
      blot analysis of IL-8 mRNA expression demonstrated a constant level during
      pregnancy with or without chorioamnionitis, indicating the possibility that the
      major site of regulation of IL-8 synthesis in the placenta is
      posttranscriptional. Immunohistochemical analysis of first and third trimester
      placental tissues with rabbit anti-IL-8 antibody revealed the IL-8 producing
      cells to be trophoblasts and macrophage-like cells. IL-8 produced by the
      placental cells might contribute to potentiation of the immunocompetence of
      placental cells against bacteria invading the fetoplacental unit.

PMID- 1391328
TI  - Histological assessment of the mouse uterus from birth to puberty for the
      appearance of LGL-1+ natural killer cells.
AB  - The appearance of natural killer (NK) cells during growth and maturation of the
      murine uterus was studied by immunohistochemistry, using the monoclonal antibody
      LGL-1. To determine the contributions of microorganisms in the environment and of
      T-cell and B-cell regulation to the establishment of a uterine NK cell
      population, uteri from barrier-raised, flora-defined, random-bred CD-1 mice and
      from genetically T-cell- and B-cell-deficient SCID mice (genotype C.B-17
      scid/scid) were compared to uteri from conventionally raised CD-1 mice. Uteri
      were studied from birth to the ages at which these mice are normally paired for
      mating (7-10 wk). Absolute uterine weight and the ratio of uterine weight to body
      weight increased remarkably between 3 and 5 wk of age in each group of animals.
      Growth continued beyond Week 5 of age, and in all groups the ratio of uterine
      weight to body weight was similar at puberty, although both the flora-defined CD
      1 and SCID mice were significantly smaller than conventionally reared mice. LGL
      1+ cells could not be detected in any of the neonatal uteri examined. LGL-1+
      cells were first detected at 2 wk of age in uteri from the conventional and flora
      defined CD-1 mice. A significant increase in the number of LGL-1+ NK cells
      occurred in the CD-1 uterus between Weeks 2 and 3 of age and again between Weeks
      5 and 7 of age. Environmental conditions did not alter the frequency of LGL-1+
      cells between the two groups of CD-1 mice at any age studied.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1391330
TI  - Isolated hypothalami from aging female rats do not exhibit reduced basal or
      potassium-stimulated secretion of luteinizing hormone-releasing hormone.
AB  - Serum LH levels are diminished in middle-aged rats during spontaneous or steroid
      induced LH surges and following ovariectomy (ovx). The compromised LH responses
      are presumed to reflect age-related alterations in LHRH neurosecretion. Direct
      measurements of LHRH output in middle-aged females are, however, limited. The
      present study utilizes an in vitro perifusion paradigm to assess basal and
      stimulated secretory capacity of LHRH neurons in isolated hypothalamic
      preparations from aging female rats. Individual hypothalamic fragments from
      middle-aged and young proestrous, ovx, and ovx, estradiol-treated females were
      perifused for 6 h and effluents were collected continuously at 10-min intervals.
      After 4 h of unstimulated output, two 10-min depolarizing pulses of KCl were
      administered. Although stimulated LHRH secretion was comparable in the two age
      groups, basal LHRH release from aging hypothalami was significantly elevated
      (pbasal less than 0.001). Furthermore, endocrine influences on LHRH output from
      aging hypothalami were less pronounced when compared to endocrine influences on
      LHRH output from young hypothalami, suggesting that steroidal regulation of LHRH
      secretion may be impaired in middle-aged females. These data demonstrate that
      LHRH neurons maintain the capacity to respond to a depolarizing stimulus at the
      time when regular estrous cycles cease and consequently suggest the importance of
      altered modulation of LHRH neurosecretion to the development of reproductive
      senescence.

PMID- 1391329
TI  - Expression of thromboxane A2 receptor gene and thromboxane A2 synthase in bovine
      corpora lutea.
AB  - Studies were undertaken to investigate the expression of thromboxane (TXA2)
      receptor gene, from mRNA to functional receptor protein in terms of ligand
      binding, along with the cellular and subcellular distribution of the enzyme that
      catalyzes the formation of the ligand for the receptors. Bovine corpora lutea
      contained a single TXA2 receptor mRNA transcript of 2.8 kb. All the cell types in
      bovine corpora lutea contained immunoreactive TXA2 synthase, TXB2, TXA2 receptor
      transcripts, and receptor protein that bound the TXA2 antagonist 9,11
      dimethylmethano-11,12-methano-16 (3-iodo-4-hydroxyphenyl)-13-14-dihydro-13-aza-15
      alpha beta-omega-tetranor TXA2. The large luteal cells (20-35 microns) contained
      more receptor transcripts, receptor protein, and immunoreactive TXA2 synthase
      than did the small luteal cells (12-19 microns), luteal blood vessels, and
      nonluteal cells (7-12 microns). After correction for the cellular area
      differences, small luteal cells were seen to contain more receptor protein than
      did large luteal cells and nonluteal cells. All the cells showed an increase of
      TXA2 receptors and catalytically active TXA2 synthase from mid-luteal phase to
      early pregnancy, suggesting the possibility that TXA2 could be a luteotropic
      eicosanoid. Bovine lung homogenates (a positive control), bovine luteal plasma
      membranes-mitochondria-lysosomes fraction, rough-smooth endoplasmic reticulum
      Golgi fraction, and highly purified nuclei contained 65-kDa immunoreactive
      protein, presumably representing TXA2 synthase. In addition, the luteal
      fractions, but not bovine lung, contained other small and large molecular-size
      immunoreactive proteins. Immunogold electron microscopy showed that
      immunoreactive TXA2 synthase was present primarily in plasma membranes, rough
      endoplasmic reticulum, nuclear membranes, and chromatin; and immunoreactive TXB2
      was present primarily in different-size vesicles and nuclear chromatin. In
      summary, the present studies demonstrate for the first time that primarily small
      and large luteal cells and secondarily blood vessels and nonluteal cells in
      bovine corpora lutea express TXA2 receptor gene along with the functional TXA2
      synthase. The presence of functional enzyme in luteal cell nuclei suggests that
      the enzyme and/or its product may have previously unrecognized functions in
      nuclei.

PMID- 1391331
TI  - A comparison of the frequency and type of chromosomal abnormalities in human
      sperm after different sperm capacitation conditions.
AB  - Human sperm karyotypes can be prepared after fusion of human sperm with Golden
      hamster oocytes. Most laboratories use one of two methods of sperm capacitation:
      incubation of freshly-ejaculated sperm in Biggers, Whitten, and Whittingham (BWW)
      medium for 5-7 h at 37 degrees C or sperm storage in (N-tris
      [hydroxymethyl]methyl-2-aminoethanesulfonic acid; 2-([2-hydroxy-1,1
      bis(hydroxymethyl)ethyl]amino)ethanesulfonic acid) (TES)-Tris yolk buffer (TYB)
      for 1-3 days at 4 degrees C. Since there have been conflicting reports as to
      whether there is a difference in the frequency of structural chromosomal
      abnormalities between BWW capacitation and storage in TYB for 2 days, we analyzed
      a larger number of karyotypes (8974) from 136 donors to determine if there was
      any difference in the frequency or type of chromosomal abnormalities in sperm
      treated by fresh BWW capacitation, storage in TYB for 1 day (TYB-1), or storage
      in TYB for 2 days (TYB-2). There was no difference in the frequency of numerical
      chromosomal abnormalities or sex ratio in any of the three treatment groups.
      However, there was a significantly increased frequency of structural chromosomal
      abnormalities after storage in TYB-1 and TYB-2. There was no difference in the
      frequency or type of structural chromosomal abnormalities after sperm storage in
      TYB-1 compared to TYB-2.

PMID- 1391332
TI  - The ability of dehydrated hamster and human sperm nuclei to develop into
      pronuclei.
AB  - To determine whether the nuclei of mature mammalian spermatozoa are resistant to
      dehydrated conditions, nuclei of hamster and human spermatozoa were freeze-dried
      or treated with various dehydrating agents before injection into hamster oocytes.
      Freeze-dried nuclei remained capable of developing into pronuclei even after 12
      mo of storage at 4 degrees C. The level of DNA synthetic activity in the sperm
      (male) pronucleus was comparable to that in the egg (female) pronucleus. Sperm
      nuclei that had been stored in 100% ethanol, 100% methanol, or chloroform
      methanol (2:1) mixture for 20 days were also capable of developing into
      pronuclei. Even the nuclei that had been dehydrated ("fixed") with Carnoy's fluid
      could develop into morphologically normal pronuclei. However, the level of DNA
      synthesis in the pronuclei derived from these chemically dehydrated nuclei was
      generally lower than that in the female pronuclei. Although the genetic integrity
      of the dehydrated sperm nuclei is yet to be determined, nuclei of mature hamster
      and human spermatozoa appear to be fairly resistant to dehydrated conditions.

PMID- 1391333
TI  - Progesterone and RU486 regulation of uterine complement C3 after prior induction
      with estradiol.
AB  - Previous results demonstrated that progesterone (P4) given simultaneously with
      estradiol (E2) prevented stimulation by E2 of complement C3 expression in the
      immature rat uterus. Northern blot analysis revealed that simultaneous
      administration of P4 was able to prevent the E2-stimulated increase in C3 mRNA
      concentration in the luminal epithelial cells. The purpose of the present
      investigation was to determine whether progesterone modulates C3 expression after
      the gene has been induced by prior administration of E2 and also to determine the
      reversibility of this effect by the concomitant administration of RU38486, 17
      beta-hydroxy-11 beta-[4-dimethylaminophenyl]estra-4,9,-dien-3-one (RU486). This
      regulation was studied by examination of protein synthesis as well as mRNA
      concentrations. Immature 21-day-old female rats were treated with E2 for 2 days
      (1 microgram/day), followed 24 h later by P4 (500 micrograms) or vehicle. Uteri
      were removed 6, 9, and 18 h after progesterone treatment and the radiolabeled
      secreted proteins were analyzed by SDS-PAGE and immunoprecipitation using a goat
      anti-rat C3 antibody. In animals treated with vehicle, E2-stimulated C3 synthesis
      remained elevated at 6 and 9 h and returned to control values by 18 h. In
      contrast, the administration of P4 resulted in a decrease in C3 synthesis at 6
      and 9 h with the greatest decrease observed at 9 h. Similar results were obtained
      when C3 mRNA concentrations were examined. E2-stimulated C3 mRNA concentrations
      were decreased in rats treated with progesterone compared to those treated with
      vehicle alone.2

PMID- 1391334
TI  - Maternal transfer of photoperiodic information in Siberian hamsters. V. Effects
      of melatonin implants are dependent on photoperiod.
AB  - Photoperiodic information is transferred from female Siberian hamsters to their
      fetuses during gestation. Although maternal melatonin is known to be essential
      for the transfer of prenatal photoperiodic information, its specific role is not
      well defined. The duration of the daily melatonin signal, expressed as an
      elevation of serum melatonin levels in the maternal circulation, has been
      hypothesized to convey day length information to the fetus. If this hypothesis is
      valid, it predicts that identical maternal melatonin signals should affect the
      fetuses identically, regardless of the prenatal photoperiod. To test this
      hypothesis, adult females received melatonin in beeswax or beeswax alone. They
      were paired with males and housed in photoperiods of 12L:12D or 16L:8D. On the
      day of parturition, mother and young were transferred to constant light (LL).
      Young males were killed on Day 28 of life, and weights of testes were determined.
      Prenatal treatment with beeswax alone did not affect the nature of the signal
      transferred from mother to fetus; young gestated in 12L:12D and reared in LL
      developed small testes, while those gestated in 16L:8D had large testes. On the
      other hand, the effect of the prenatal melatonin treatment on postnatal
      testicular development in LL was inversely dependent on the prenatal photoperiod:
      testicular growth was stimulated in young gestated in 12L:12D, but inhibited in
      young gestated in 16L:8D. To verify that the melatonin pellets produced
      equivalent serum melatonin levels in adult females in 12L:12D and 16L:8D, unmated
      adult females were killed 6-10 wk after receiving melatonin pellets. Serum levels
      were elevated in both groups throughout the day and night.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1391335
TI  - Hypotaurine requirement for in vitro development of golden hamster one-cell
      embryos into morulae and blastocysts, and production of term offspring from in
      vitro-fertilized ova.
AB  - Almost 30 years after the first successful in vitro fertilization (IVF) in golden
      hamsters (Mesocricetus auratus), we report that IVF hamster embryos can develop
      in a chemically defined, protein-free culture medium into morulae and
      blastocysts, and produce normal offspring after transfer to recipients. When
      examined 96 h post-insemination, 82% (160/200) of IVF ova had cleaved to at least
      2 cells, 55% (97/200) had developed beyond the 4-cell stage, and 22% (38/200) had
      developed into morulae/blastocysts. In vitro development of IVF embryos to
      greater than or equal to 8 cells was absolutely dependent on hypotaurine. Twenty
      living offspring were produced from transfer of IVF embryos to recipients, with
      an overall success rate of 5% and 17% for oviductal (2-cell) and uterine (8
      cell/morulae) transfers, respectively. In vivo-fertilized pronucleate embryos
      collected 3 h after egg activation were less able to develop in vitro than
      embryos collected only 6 h later, revealing a critical influence of the oviduct
      within the first hours of embryo development. Hypotaurine partly compensated for
      the decreased oviductal exposure of early 1-cell embryos. Establishment of a key
      role for hypotaurine in hamster embryo development, support of IVF embryos to
      morula/blastocyst stages in vitro, and production of living offspring after IVF
      embryo transfer are significant steps towards the goal of obtaining comparative
      data on preimplantation embryogenesis.

PMID- 1391336
TI  - Cloning of the porcine Calbindin-D9k complementary deoxyribonucleic acid by
      anchored polymerase chain reaction technique.
AB  - The Calbindin-D9k (CaBP-9k) is a cytosolic calcium binding protein expressed in
      the mammalian intestine, placenta, and uterus. The protein is probably involved
      in calcium transport across the intestinal and placental epithelia. In uterus, a
      function in controlling myometrial activity involving intracellular calcium has
      been postulated. The amino acid sequence of the porcine CaBP-9k has been
      determined from intestine. The cDNAs for the bovine, murine, and rat CaBP-9k have
      been cloned. The objective of this study was the cloning of the porcine cDNA
      encoding the CaBP-9k. We performed the anchored polymerase chain reaction (PCR)
      technique using rat and bovine cDNA sequence-derived primers for amplification of
      intestinal cDNA. Both 5' and 3' amplification products were cloned and sequenced.
      The sequences revealed the full-length cDNA encoding the porcine CaBP-9k, coding
      region for 79 amino acids, 57 nucleotides 5' and 149 nucleotides 3' noncoding
      region. The inferred amino acid sequence is identical to the published amino acid
      sequence, except for one residue. The porcine CaBP-9k cDNA is 82.8% and 69.1%
      homologous with the bovine and rat sequences, respectively. Both bovine and
      porcine cDNAs contain a stretch of approximately 50 nucleotides not found in the
      rat sequence. Northern analysis showed a 600 nucleotide transcript in intestine,
      kidney, and uterus.

PMID- 1391337
TI  - Flow cytometric analysis of steroidogenic organelles in differentiating granulosa
      cells.
AB  - Functional and structural changes accompany the differentiation of granulosa
      cells during follicular development. We used flow cytometry and fluorescent dyes
      to characterize two organelles important to the steroidogenic process.
      Mitochondria, which contain the rate-limiting enzyme responsible for cholesterol
      conversion to pregnenolone, and lipid droplets, which store cholesterol
      substrate, were probed in viable hen granulosa cells during differentiation. The
      fluorescent dye Dio3-C5 (DiO) was used to probe mitochondrial membrane potential,
      indicative of mitochondrial activity and/or number, during rapid granulosa cell
      differentiation in a hierarchy of individual developing hen preovulatory
      follicles (F6, smallest, to F1, largest). Cellular DiO fluorescence, granularity,
      and cell size were significantly elevated with increasing maturation state.
      Treatment with LH significantly increased DiO fluorescence in granulosa cells
      from F1 but not F3. The increased mitochondrial activity/number in granulosa
      cells that accompanies follicular maturation and is influenced by LH may reflect,
      at least in part, increased activity or amount of hormone-regulated mitochondrial
      enzymes controlling steroidogenesis. Flow spectrofluorometry and the
      metachromatic lipid dye, nile red, were used to probe lipid droplets in
      differentiating granulosa cells from F6 to F1. There was a dramatic increase in
      the fluorescence component related to lipid droplets with increasing stages of
      follicular maturation, suggesting recruitment of lipids into droplets during the
      differentiation of granulosa cells into hormone-responsive steroidogenic cells.
      The results demonstrate the dynamic nature of the granulosa cell morphology
      involved in steroidogenesis during follicular development.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1391338
TI  - Synthesis and secretion of retinol-binding protein by cultured rat Sertoli cells.
AB  - We report here that retinol-binding protein (RBP) is synthesized and secreted by
      rat Sertoli cells in culture. This was demonstrated in four ways. First,
      transthyretin (TTR) bound to Sepharose 4B retained a labeled protein from media
      collected from Sertoli cells provided with 35S-methionine, under the same
      conditions as authentic RBP is bound. The protein was co-eluted with authentic
      RBP by pure water. Second, this same radioactive protein co-eluted with pure RBP
      upon gel filtration. Third, when subjected to SDS-PAGE, the protein again
      migrated with pure RBP, as shown by radioautography. Finally, Sertoli cells were
      incubated with 35S-cysteine and the conditioned medium was put over a TTR
      Sepharose column to isolate the radioactive protein, as characterized above.
      Cysteine residues were oxidized to cysteic acid residues, and the protein was
      submitted for sequencing through the first ten residues. Radioactivity was
      located only in the fourth residue, where a cysteine residue is found in rat RBP.
      This indicates that RBP is secreted by the Sertoli cell and may serve as the
      carrier of retinol to the developing germ cells, which are known to be dependent
      upon vitamin A.

PMID- 1391339
TI  - Prolactin stimulates the expression of luteinizing hormone/chorionic gonadotropin
      receptor messenger ribonucleic acid in the rat corpus luteum and rescues early
      pregnancy from bromocriptine-induced abortion.
AB  - Timed pseudopregnancy (psp) and pregnancy were induced in adult female rats by
      mating with infertile and fertile males, respectively. Corpora lutea (CL) and the
      residual parts of the ovaries were isolated and analyzed for luteinizing
      hormone/chorionic gonadotropin (LH/CG) receptor mRNA by Northern blot and
      solution hybridization analyses. Several LH/CG receptor mRNA transcripts were
      detected that could code for an intact functional receptor (6.8, 4.4, and 2.6 kb)
      as well as several smaller truncated transcripts. LH/CG receptor mRNA abundance
      in CL varied dramatically during both psp and pregnancy, with peak levels seen
      during the period of maximal progestational activity (Days 5-10 of psp and Days 7
      14 of pregnancy). During the period of functional luteolysis, LH/CG receptor mRNA
      abundance decreased to low levels. The changes in LH/CG receptor expression could
      be explained by hormonal regulation. Bromocriptine treatment inhibited pituitary
      prolactin secretion. This treatment had a potent luteolytic effect by decreasing
      the levels of LH/CG receptor mRNA and plasma progesterone during early pregnancy,
      resulting in embryonal resorption in pregnant rats. Exogenous prolactin acted as
      a anti-luteolysin to reverse these effects by restoring LH/CG receptor mRNA
      abundance either by increasing gene expression or by stabilizing mRNA transcripts
      from degradation in young CL.

PMID- 1391340
TI  - Sex ratio manipulation in wild house mice: the effect of fetal resorption in
      relation to the mode of reproduction.
AB  - First generation laboratory-born descendants of wild-caught house mice (Mus
      musculus domesticus Rutty) were bred to produce litters of primipares and of dams
      that had conceived a second litter either after lactational anestrus or within
      the postpartum estrus. At the day of birth, pups were sexed and the number of
      implanted and resorbed embryos was determined to evaluate the influence of mode
      of reproduction on litter gender composition and its relation to fetal
      resorption. No significant deviations from an even sex ratio occurred in the
      sample. The results indicate that primipares produced litters with subnormal
      dispersion of the gender distribution, but this could not unequivocally be
      attributed to fetal resorption. No significant bias in the litter gender
      composition was detectable within litters conceived after lactational anestrus.
      In contrast, the dispersion of the gender distribution was significantly
      supernormal in the litters of dams inseminated at postpartum estrus. Within this
      group, fetal resorption had a significant effect upon the sex ratio, and this
      relationship was significantly affected by the number of implanted embryos:
      resorbing dams produced male-biased litters at small and intermediate numbers of
      implantation sites and female-biased litters when the number of implanted embryos
      was large. It is argued that this is most likely attributable to sex-selective
      fetal resorption.

PMID- 1391341
TI  - Evidence that most of the radioimmunoassayable inhibin secreted by the corpus
      luteum of the common marmoset monkey is of a non-dimeric form.
AB  - Although recent data for several species of primate, including human and
      marmoset, indicate that the corpus luteum secretes high levels of
      radioimmunoassayable inhibin, the nature of the immunoreactive (ir) inhibin
      detected has not been established. In this study, plasma ir-inhibin levels during
      the ovarian cycle of the marmoset (n = 12 animals) were measured by alpha-subunit
      directed inhibin RIA, and values were compared with those estimated by a recently
      developed two-site immunoradiometric assay (IRMA) specific for inhibin alpha-beta
      dimer. Consistent with earlier data, plasma levels of ir-inhibin measured by RIA
      (overall mean value 133 +/- 7 ng/ml; n = 171) reached values 4-fold higher (p
      less than 0.001) during the luteal phase (222 +/- 20 ng/ml) than during the
      follicular phase (58 +/- 8 ng/ml), being directly correlated with plasma
      progesterone levels (r = 0.65; p less than 0.001). In contrast, plasma ir-inhibin
      levels estimated by IRMA were substantially lower than those measured by RIA
      (overall mean value 9.62 +/- 1.08 ng/ml; n = 171) and did not vary significantly
      during the cycle. Administration of a luteolytic dose of cloprostenol during the
      late luteal phase/early pregnancy led to an abrupt fall in plasma concentrations
      of progesterone (95%) and alpha-inhibin measured by RIA (82%), whereas dimeric
      inhibin levels remained unchanged. Analysis of marmoset luteal extracts (n = 5)
      by RIA, IRMA, and inhibin bioassay yielded inhibin estimates of 102.6 +/- 21.0,
      0.632 +/- 0.103, and less than 2.0 ng/mg, respectively, thus confirming that only
      a very small proportion of the inhibin produced was dimeric (i.e., bioactive) in
      nature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391342
TI  - Reversal of reproductive deficiency in the hpg male mouse by neonatal
      androgenization.
AB  - Some aspects of reproductive function in the GnRH-deficient hypogonadal (hpg)
      mutant mouse can be restored by transplanting normal fetal brain tissue
      containing GnRH cells into the central nervous system of adult hpg mice. However,
      hpg males showing physiological response to the graft fail to display sexual
      behavior and are infertile. We hypothesized that the reproductive deficit of
      these males is due to insufficient perinatal exposure to testicular androgens as
      a consequence of the GnRH deficiency. To test this hypothesis we androgenized hpg
      males by giving them neonatal injections of testosterone propionate (TP).
      Controls consisted of hpg males not androgenized neonatally and of normal males.
      All three groups received a TP implant in adulthood, and their copulatory
      behavior and reproductive capability were recorded. In addition, other hpg males,
      not androgenized neonatally, received fetal brain transplants containing GnRH
      neurons and were also tested for copulatory behavior and reproductive capability
      before and after receiving a TP implant. Three of 8 neonatally androgenized hpg
      males expressed the full repertoire of male sexual behavior, including
      intromission and ejaculation, and sired several litters. Three of 7 control hpg
      males that were not androgenized neonatally but received TP implants in adulthood
      also displayed mounting and intromission, but there was no evidence of
      ejaculation, and these males failed to impregnate normal females. Of the 8 hpg
      males that responded to a fetal transplant with testicular growth, only 1
      displayed mounting behavior. However, when given a TP implant, 4 of 8 hpg males
      with grafts displayed mounting and intromissions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391343
TI  - Testins are localized to the junctional complexes of rat Sertoli and epididymal
      cells.
AB  - Testin I and Testin II were originally identified as Sertoli cell products with
      similar NH2-terminal amino acid sequences. Secretion of testins is stimulated by
      testosterone in Sertoli cell-enriched cultures. By contrast the secretion of
      testins from intact seminiferous tubules appears to be inversely related to germ
      cell number. In the present study testin antiserum that recognized both Testin I
      and Testin II ("testin") was used to localize these proteins in tissue secretions
      by immunofluorescence. Testin was localized at the base of the seminiferous
      epithelium at Sertoli-Sertoli junctions. Fluorescence also appeared to be located
      at the sites of interaction between spermatoids and Sertoli cells. A punctate
      pattern of fluorescence was also present in the cytoplasm of Leydig cells;
      without electron microscopic studies it was not possible to determine which
      structures the antibodies bound to in these cells. In the epididymis the reaction
      product was localized at the apices of the epithelial cells adjacent to the lumen
      at the sites of known junctional complexes. A variety of positive and negative
      controls indicated that staining was specific for testins. CONCLUSIONS: This is
      the first study to associate testins with junctional complexes. Relative to other
      junctional proteins, testins are unusual because of their small size and because
      they are secreted proteins.

PMID- 1391344
TI  - Effects of follicle-stimulating hormone on inhibin release by different
      testicular compartments in the adult ram.
AB  - The aim of this study was to determine the bidirectional release of
      immunoreactive inhibin-alpha (irINH-alpha) by different testicular compartments
      in the adult ram and to assess the effects of FSH on the distribution of inhibin
      in the testis. Immunoreactive INH-alpha was measured by RIA in fluid samples
      collected concurrently from the three testicular compartments--the seminiferous
      tubules, the interstitium, and the vascular system--through catheters inserted
      surgically into the rete testis, testicular lymphatic duct system, and spermatic
      veins, respectively. Overall, the concentration of irINH-alpha in rete testis
      fluid was 25 times the level in testicular lymph and over 500 times the
      concentration in peripheral blood. The pattern of irINH-alpha concentration in
      rete testis fluid was inversely related to that in testicular lymph, but i.v.
      administration of FSH had a decoupling effect on this relationship by depressing
      inhibin concentration in testicular lymph without affecting inhibin levels in
      rete testis fluid. Nevertheless, increased flow of testicular lymph more than
      compensated for the transient fall in irINH-alpha concentration so that, overall,
      the total output of inhibin via the testicular lymphatic duct system (and the
      vascular system) increased significantly. No persistent or significant changes
      were observed in the flow rate of rete testis fluid or concentration of irINH
      alpha in the fluid after administration of FSH. The time frame for the response
      of the testis to FSH is indicative of the involvement of a mediator.
      Electrophoretic analysis of serially collected testicular lymph samples
      consistently revealed an FSH-induced release of a series of proteins in the M(r)
      range of 30,000-32,000.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391345
TI  - Maternal plasma catecholamines in the rhesus macaque during late gestation:
      effect of photoperiod and timed melatonin infusion.
AB  - This study tested the hypothesis that changes in photoperiod alter plasma
      catecholamine concentrations in the rhesus monkey during late gestation. Twelve
      chronically catheterized pregnant rhesus macaques were acclimated to a 12-h
      photoperiod (lights-on, 0700-1900 h). Under the control L:D cycle, blood samples
      were collected at 3-h intervals over 24 h for catecholamine analysis. Plasma
      concentrations (mean +/- SEM, pg/ml) ranged from 678 +/- 90 to 928 +/- 142 for
      norepinephrine; 230 +/- 22 to 631 +/- 141 for epinephrine; and 282 +/- 70 to 1090
      +/- 362 for dopamine. A diurnal rhythm was observed in epinephrine with peak
      concentrations during lights-on (0900-1800 h; p less than 0.05, compared to
      lights-off). After the first sampling protocol, the animals were divided equally
      between two groups: phase shift, in which lights-on was shifted 11 h (2000-0800
      h) and constant light, with lights on continuously. After the phase shift, a
      parallel shift in the plasma epinephrine rhythm was noted, with peak levels
      observed between 2200 and 0700 h (p less than 0.05). Constant light abolished the
      rhythm in epinephrine, with an overall reduction in mean basal levels of all
      three catecholamines. Daily melatonin infusions (0.2 micrograms/kg/h, 1900-0630
      h) under constant light failed to restore the epinephrine rhythm or to return
      basal catecholamine concentrations to control photoperiod levels. These data
      suggest that photoperiod entrains the rhythm in epinephrine secretion, but the
      rhythm is ablated under constant conditions. Further, melatonin does not appear
      to play a role in the regulation of catecholamine secretion in the pregnant
      rhesus macaque.

PMID- 1391346
TI  - Binding of epididymal proteins to rat spermatozoa in vivo.
AB  - The secretion of epididymal proteins and their binding to spermatozoa in rats
      were examined after retrograde perfusion of the superior and inferior epididymal
      arteries with [35S]methionine. PAGE revealed that the pattern of radioactive
      proteins in the luminal fluid was markedly different from the well-characterized
      pattern of secretory proteins obtained by in vitro incubation of epididymal
      minces with labeled methionine. Of the proteins secreted into the lumen, about 1%
      were associated with Percoll-purified spermatozoa. More proteins were associated
      with the spermatozoa in the corpus epididymidis than in the caput. Sequential
      extraction of spermatozoa with an isotonic buffer, a high-salt buffer, Triton X
      100, and SDS revealed that almost half of the radiolabeled proteins could be
      extracted with the isotonic buffer. The firmly bound radioactive proteins
      remaining, which were extracted with Triton X-100 or SDS, consisted of one major
      band of 25 kDa and two minor bands of 30 kDa and 32 kDa. Analysis of the sperm
      associated proteins at various times after the isotope was administered indicated
      that tight binding of proteins to spermatozoa occurs within 3 h after isotope
      injection.

PMID- 1391348
TI  - In situ localization and characterization of bone marrow-derived cells in the
      decidua of normal murine pregnancy.
AB  - The study reported here was designed to examine the in situ distribution and
      characteristics of hemopoietically derived decidual cells during normal pregnancy
      in mice prenatally reconstituted with bone marrow cells carrying a transgenic
      marker. Bone marrow cells from a transgenic CD-1 strain (CD-1 beta; carrying 1000
      copies of beta-globin genes in tandem) were injected into the yolk sac of Day 17
      conventional CD-1 embryos. The pregnant females were allowed to deliver normally,
      and the female offspring raised to puberty were mated with CD-1 males and then
      killed on Day 12 of gestation. The extent of chimerism in sections of their
      spleens, uteri, and other organs was evaluated by in situ hybridization of the
      sections with a biotinylated cDNA probe specific for the beta-globin genes
      followed by avidin-biotin-peroxidase staining. Tissue controls were provided by
      CD-1 beta and CD-1 mice, respectively. Tissues were also processed without the
      application of the probe or with the application of biotinylated lambda DNA as
      specificity controls. Reconstituted mice exhibited variable degrees of
      hemopoietic chimerism as indicated by labeling of their splenic lymphocytes (18
      54%; mean 42%) as well as hemopoietic cells in other organs. Variable cellular
      labeling was also noted in their decidua basalis and metrial glands. Labeled
      cells in these tissues were identified as typical decidual cells, macrophages,
      and granulated metrial gland (GMG) cells. Labeling of typical decidual cells
      varied extensively among implantation sites in the same chimera, the average
      labeling ranging from 17% to 33% (mean 24%) in various chimeras. Labeling was
      also noted in GMG cells, lymphocytes, and some decidual cells migrating out of
      metrial gland explants after 24-h culture. The non-pregnant uterus of a chimeric
      mouse revealed significant labeling of endometrial stromal cells indicative of
      their hemopoietic origin. These results revealed a hemopoietic origin of certain
      typical decidual cells and GMG cells identified in situ during normal murine
      pregnancy and a hemopoietic origin of certain endometrial stromal cells that may
      represent precursors of decidual cells. The precise timing of the predecidual
      stem cell migration from the bone marrow to the uterus remains to be defined.

PMID- 1391347
TI  - Pituitary luteinizing hormone and prolactin messenger ribonucleic acid levels are
      inversely related in laying and incubating turkey hens.
AB  - The relationships of prolactin (PRL) and LH messenger (m) RNA to serum and
      pituitary content were determined for turkey hens at different phases of the
      reproductive cycle. In the nonphotostimulated, reproductively inactive hen, serum
      and pituitary PRL content and pituitary PRL mRNA levels were low. All three PRL
      values rose after photostimulation and peaked during the incubation phase.
      Relative to nonphotostimulated hens, hyperprolactinemic incubating hens showed
      220-, 11-, and 57-fold increases in serum PRL, pituitary PRL content, and
      pituitary PRL mRNA levels, respectively. These peak levels declined 80-, 3-, and
      6-fold, respectively, in photorefractory hens. In contrast to PRL levels, serum
      LH, pituitary LH, and pituitary LH beta-subunit mRNA levels did not change as
      dramatically. Serum LH showed no significant changes for the different
      reproductive phases. Pituitary LH peaked after photostimulation and declined to
      its lowest level in incubating hens. Pituitary LH-beta mRNA abundance was highest
      in photostimulated and laying hens and lowest in incubating and photorefractory
      hens. These results demonstrate that the abundance of LH-beta and PRL mRNA shows
      an inverse relationship in photostimulated/laying and incubating turkey hens.

PMID- 1391349
TI  - Impaired transport and fertilization in vivo of calcium-treated spermatozoa from
      +/+ or congenic tw32/+ mice.
AB  - To determine whether calcium alters processes important for fertilization in
      vivo, mouse (+/+) spermatozoa were incubated in medium with 1.0-1.7 mM calcium
      prior to artificial insemination (AI) into the cervix of hormonally primed
      females. Spermatozoa from congenic tw32/+ mice were also tested because their
      flagella are hypersensitive to calcium. As a control, spermatozoa were incubated
      in calcium-deficient medium prior to AI. Spermatozoa from mice of both genotypes
      incubated in calcium-containing medium fertilized significantly fewer eggs after
      AI than did spermatozoa incubated in calcium-deficient medium. In addition,
      calcium-treated spermatozoa from tw32/+ mice fertilized significantly fewer eggs
      than calcium-treated +/+ spermatozoa. Pretreatment with calcium also reduced the
      number of spermatozoa in the oviducts 0.5-4.5 h after AI, and the oviducts of
      females inseminated with calcium-treated spermatozoa from tw32/+ mice contained
      significantly fewer spermatozoa than those of females inseminated with calcium
      treated +/+ spermatozoa. These results suggest that preincubation in millimolar
      levels of calcium changes the physiology of epididymal spermatozoa in such a way
      as to impair sperm transport to the oviduct and fertilization in vivo.

PMID- 1391350
TI  - Calcium alters capacitation and progressive motility of uterine spermatozoa from
      +/+ and congenic tw32/+ mice.
AB  - The importance of calcium-dependent sperm processes for fertilization in vitro is
      well known, but their interaction with sperm transport in vivo is not yet clear.
      To determine whether exposure to calcium alters sperm physiology after incubation
      in the uterus, spermatozoa from +/+ mice were incubated in medium with 1.7 mM
      calcium prior to artificial insemination (AI). Spermatozoa from congenic tw32/+
      mice were also tested because their flagella are hypersensitive to calcium. As a
      control, spermatozoa were incubated in calcium-deficient medium before AI. When
      recovered from the uterus 60 min post-AI, neither prior exposure to calcium nor
      genotype affected numbers of spermatozoa, or percentage of motile or acrosome
      reacted spermatozoa. However, significantly more calcium-treated spermatozoa were
      capacitated and significantly fewer were progressively motile than spermatozoa
      preincubated without calcium. In addition, significantly fewer spermatozoa from
      tw32/+ mice than from +/+ mice were progressively motile. These results suggest
      that uterine sperm physiology is changed by prior exposure of sperm to calcium.
      Since the level of progressive motility of spermatozoa recovered from the uterus
      was correlated with their ability to reach the oviduct (as determined in a
      previous study), these data support the hypothesis that progressive motility of
      uterine spermatozoa is important for passage to the oviduct and fertility.

PMID- 1391351
TI  - Nuclear totipotency of cultured rabbit morulae to support full-term development
      following nuclear transfer.
AB  - The rabbit was used as a model for nuclear transfer. A critical step in nuclear
      transfer is oocyte activation, which was evaluated in this research. Optimal
      field strength of an electric stimulus for activation was examined. A
      significantly higher activation rate in all criteria tested was achieved when
      oocytes were activated electrically with a field strength of 2.4 kV/cm versus 1.2
      or 1.8 kV/cm. Also, electrical stimulation with combined alternating current (AC)
      and direct current (DC) was superior to DC stimulation alone for activation. In
      another study involving 586 oocytes, exposure of oocytes to cytochalasin B for 1
      h followed by activation with electrical stimulation significantly improved
      development of the oocytes to blastocyst stage compared to oocytes without
      cytochalasin B pre-exposure (38% vs 26%, p less than 0.05). Cytochalasin B
      exposure alone (control), however, had no effect on activation. Exposing oocytes
      to activation medium without electrical stimulation also activated some oocytes.
      In the nuclear transfer experiment, blastomeres from 8-cell embryos cultured for
      20-24 h to the 32-64-cell stage were used as nuclear donor cells. Of 491 oocytes
      used, 459 (93%) survived the enucleation and fusion procedure, 370 (81%) fused,
      and 284 (77%) developed into 2-4-cell embryos. A total of 243 of these 2-4-cell
      embryos were transferred to 15 pseudopregnant recipients and produced 8 young
      (3%). Although the efficiency is low, this study demonstrated that rabbit morulae
      cultured for 20-24 h to the 32-64-cell stage as nuclear donors for transfer
      remain totipotent.

PMID- 1391352
TI  - Steroid hormone content of the gonads of the tammar wallaby during sexual
      differentiation.
AB  - The gonads of the tammar wallaby, Macropus eugenii, are sexually indifferent at
      birth (Day 0) despite the fact that phenotypic sexual differentiation has already
      commenced as evidenced by the presence of a scrotum in males and mammary anlagen
      in females. The seminiferous cords of the testis first become clearly
      recognizable on Day 2 of pouch life, and ovarian differentiation is recognizable
      by Day 10. To monitor the endocrine development of the gonads during sexual
      differentiation of the urogenital tract, we measured the steroid hormone content
      in 92 pools of gonads from male and female tammar pouch young from the day of
      birth to 206 days of pouch life. Progesterone, estradiol, and dihydrotestosterone
      concentrations were low (less than 0.05 ng/mg protein) in both ovaries and testes
      at all stages examined, and testosterone concentrations were uniformly low in
      ovaries. Testosterone concentrations in testes were low on Days 0-4, averaging
      about 0.2 ng/mg protein; they rose by Days 5-10 to an average of 0.9 ng/mg
      protein, remained elevated until about Day 40, and thereafter fell to values
      similar to those in the ovaries. The phallus and urogenital sinus were able to
      convert testosterone to dihydrotestosterone from the earliest stages examined
      (Days 10 and 11). Thus in the tammar wallaby, as in eutherian mammals,
      testosterone is the androgen secreted by the developing testis, and
      dihydrotestosterone is formed in certain androgen target tissues.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1391353
TI  - Follicular heterogeneity and oocyte maturation in vitro in pigs.
AB  - Experiments were conducted to confirm that co-culture of follicular shells and
      immature pig oocytes improved the rate of male pronuclear (MPN) formation and to
      test the hypothesis that the maturational state of the follicle used in co
      culture would significantly affect the quality of oocytes matured in vitro. In a
      preliminary experiment, co-culture of oocyte complexes with follicular shells did
      not affect nuclear maturation, slightly inhibited penetrability (p = 0.04) but
      greatly enhanced (p = 0.0004) MPN rate. In the main experiment, oocyte complexes
      (10-15 per dish), obtained from follicles 36 h after eCG injection of prepubertal
      gilts, were co-cultured with single 36-h small (3.5-5.0 mm), 36-h large (6-9 mm),
      72-h small (4-7 mm), or 72-h large (7.5-11.0 mm) follicular shells prior to
      insemination. MPN formation in penetrated oocytes was significantly affected by
      follicular size (small: 60.14% vs. large: 72.08%, p = 0.014) but not by time of
      recovery (36 h: 72.32% vs. 72 h: 59.90%, p = 0.39). Overall, MPN formation rate
      was significantly correlated with follicular diameter (r = 0.45, p = 0.005),
      follicular fluid progesterone (r = 0.37, p = 0.02), and estradiol (r = 0.40, p =
      0.01), and to the ratios of follicular fluid progesterone:testosterone (r = 0.39,
      p = 0.018) and follicular fluid estradiol:testosterone (r = 0.43, p = 0.007).
      There were no simple correlations between rate of MPN formation and steroid
      concentrations and their ratios in culture media collected at the completion of
      culture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391354
TI  - Leydig cells express neural cell adhesion molecules in vivo and in vitro.
AB  - The neural cell adhesion molecule (NCAM) polypeptides are expressed by numerous
      tissues during embryonic development, where they are involved in cell-cell
      interactions. In the adult, NCAM expression is confined to a few cell types,
      including neurons and peptide-hormone-producing cells. Here we demonstrate that
      the Leydig cells of the adult rat, mouse, and hamster testes express NCAM as
      well. Western blotting showed that an NCAM of approximately 120 kDa was present
      in the adult testes of all three species investigated. This form was also found
      in freshly isolated mouse Leydig cells and in Leydig cells after 2 days in
      culture. After 4 days in culture, mouse Leydig cells expressed additional NCAM
      isoforms of approximately 140 and 180 kDa, indicating changes in alternative
      splicing of NCAM primary transcripts. Also, NCAM mRNA of all isoforms, as
      detected by S1-nuclease protection assays, increased with time in culture. The
      expression of the cell adhesion molecule NCAM by adult Leydig cells may explain
      the aggregation of Leydig cells in clusters in rodent testes, which could be a
      prerequisite for functional coordination of groups of Leydig cells. Furthermore,
      the presence of this neural and endocrine marker may indicate a closer
      relationship between Leydig cells and neural and peptide-hormone-producing cells
      than is considered to exist at the present time.

PMID- 1391355
TI  - [The molecular action profile of intravenous anesthetics].
AB  - A close look at the molecular interactions of intravenous anaesthetics reveals a
      complex and non-uniform picture. A multitude of membrane structures are affected
      by the individual anaesthetic compounds, although with specific differential
      profiles of molecular action for the different groups of anaesthetic substances.
      This is consistent with the hypothesis of a multi-mechanistic mode of action,
      where anaesthesia results from the superposition and integration of several
      anaesthetic actions on the molecular level. This overall concept is illustrated
      by using the well characterised voltage-activated human brain sodium channel
      protein and its interactions with various intravenous anaesthetics as an example
      for other membrane proteins. Using the novel lipid bilayer "voltage-clamp"
      technique, single sodium channels were incorporated into artificial lipid
      bilayers and their single channel properties studied. Compared to controls, all
      studied anaesthetics (propofol, pentobarbital, ketamine, midazolam) interacted in
      a dose-dependent manner with two key sodium channel functions: 1. reduction of
      the voltage-independent fractional channel open-time and 2. interaction with the
      voltage-dependent steady-state activation process. Only propofol and
      pentobarbital demonstrated these effects at clinically relevant concentrations;
      hence, the sodium channel might serve as a molecular site of action for these
      substances only. Differences between clinical anaesthetics and their clinical
      actions may thus correlate with differential molecular sites and modes of action.

PMID- 1391356
TI  - [Early detection of traumatic aortic aneurysms using transesophageal Doppler
      echocardiography].
AB  - The early diagnosis of traumatic aortic dissections and aneurysms involving the
      thoracic aorta is of crucial importance for the outcome of patients suffering
      chest injuries. This subject is presented using two case reports; one illustrates
      the problems resulting from an overlooked traumatic aneurysm of the thoracic
      aorta and the second shows the possibilities of detecting such potentially lethal
      injuries early in patients with thoracic or multiple injuries, using the
      transesophageal Doppler echocardiography (TDE). The advantages and disadvantages
      of using TDE as compared to the more conventional methods such as the precordial
      Doppler echocardiography, computed tomography and angiography, are discussed. The
      particular advantage of this hardly invasive or burdening method is its immediate
      availability in the emergency room to assess patients with evident thorax trauma.
      In the intensive care unit TDE may be of value in screening polytraumatised
      patients who offered no primary evidence for chest injury upon arrival.

PMID- 1391358
TI  - [Historical vignette (2). Asphyxia caused by chewing tobacco during chloroform
      anesthesia].

PMID- 1391357
TI  - [Extreme duration of action of diazepam as a cause of respiratory insufficiency
      in a female geriatric patient].
AB  - A 77-year-old woman who had undergone surgery of a non-malignant extracerebral
      retro-orbital tumor suffered postoperatively from respiratory failure due to
      impaired respiratory drive and unconsciousness of unknown origin and required
      artificial ventilation for 14 days. After cerebral and endocrinological causes
      had been excluded, the residual effects of diazepam were taken into
      consideration, since the patient had received this substance for premedication
      and during 3 days postoperatively (total 165 mg). After the application of
      flumazenil (Anexate), a specific benzodiazepine receptor antagonist, she awoke
      immediately and was extubated with sufficient spontaneous breathing. The
      hypothesis that diazepam was the causative agent for the respiratory failure and
      impaired consciousness was supported by the detection of high serum
      concentrations of diazepam and its active metabolite desmethyldiazepam. During
      the following 3 days repetitive injections of flumazenil were necessary to
      counteract recurring depression of respiration and vigilance. Thereafter further
      application of flumazenil was not necessary.

PMID- 1391359
TI  - [Research structure and support in anesthesiology--a 10-year outlook].

PMID- 1391361
TI  - [The spontaneous and evoked EEG in anesthesia].
AB  - Clear differentiation between nociception and pain, or, better, between anti
      nociception and pain relief, is essential for understanding the analgesic
      mechanisms in anaesthesia. Nociception is a neuronal activity in the pain
      mediating and pain-processing nervous system, i.e. in the peripheral axons, in
      the spinal short cord and in certain brain structures. The nociceptive system has
      been well documented by experiments, especially in animals. If this system is
      specifically blocked, there will be no transmission and hence no sensation of
      pain if we leave aside the rare and complicated instances of "psychogenic pain".
      Nociceptive activity is blocked or at least attenuated by anti-nociceptive drugs,
      such as surface anaesthetics acting in the periphery by blocking the sodium
      channels in the conductive nerve membrane. Opiates are another example of drugs
      which develop an effect on specific nociceptive neurons in the spinal cord and in
      the brain, thus suppressing pain transmission. An ideally effective anaesthetic
      should act similarly, that is by specifically and selectively suppressing
      nociceptive activity induced by surgery. However, general anaesthesia is based on
      entirely different mechanisms. It lowers the arousal level, or the vigilance of
      the patient. Since pain is the conscious processing of nociceptive information,
      attenuating the vigilance also alleviates pain; there is no pain without
      consciousness. Most of the centrally acting analgesics will also reduce
      vigilance; e.g. driving is not permitted under analgesia with opiates. Alcohol is
      another example, although it minimally affects the nociceptive system, it
      substantially lowers the vigilance, thereby alleviating pain.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1391360
TI  - [The anesthetic site of action: from the intact brain to the isolated protein. An
      overview].
AB  - To the present day there is no consensus of opinion as to which molecular events
      lead to the complex clinical state generally referred to as anaesthesia. The
      multitude of simultaneous physiological changes are also responsible for this
      lack of consensus. During anaesthesia, for example, consciousness, perception,
      memory, pain, and muscle relaxation are altered. The actions of anaesthetics
      correlate very well with their partitioning into lipophilic phases. Lipophilic
      interactions are non-specific. Therefore, it is likely that anaesthetics act at
      many different sites. Cell membranes are not the only possible sites but also
      membrane proteins and the various hydrophobic domains they contain. The multitude
      of clinical anaesthetic effects is paralleled by the complexity of molecular
      interactions. A better understanding of anaesthesia requires an integrated view
      of anaesthetic effects at the various systemic levels, beginning with the
      molecular domain and ending with the intact central nervous system. Anaesthesia
      research could be directed more towards man because it has now become possible to
      conduct molecular in-vitro studies with human cells as well as non-invasive
      studies of the intact human central nervous system.

PMID- 1391362
TI  - [Current concepts on the adult respiratory distress syndrome].

PMID- 1391363
TI  - [Acute respiratory failure--support of gas exchange using extracorporeal or
      implanted oxygenators--present status and future development].
AB  - In acute respiratory failure gas exchange can be supported or even maintained in
      an "alternative" way to mechanical ventilation using extracorporeal techniques
      (extracorporeal membrane oxygenation ECMO, extracorporeal CO2-removal ECCO2R), or
      intravenacaval oxygenators (IVOX). These techniques, which are currently in use
      in neonatology, pediatrics, and adult intensive care medicine, or techniques at
      present in clinical evaluation (IVOX), are reviewed with their indications,
      contraindications, differences, problems, worldwide results, and possible future
      applications.

PMID- 1391364
TI  - [Potential risks of high-dose adrenaline for resuscitation following short-term
      heart arrest in animal experiments].
AB  - We compared the haemodynamic effects of epinephrine 10 micrograms/kg iv (group A,
      n = 8) and 50 micrograms/kg iv (group B, n = 8) in a porcine CPR-model after 3
      min of circulatory arrest induced by ventricular fibrillation. All animals of
      group A were successfully resuscitated after 4.9 +/- 2.8 min and 2.8 +/- 1.6
      defibrillations, in group B only 6 of 8 animals were successfully resuscitated
      after 6.3 +/- 1.1 min and 4.0 +/- 2.7 defibrillations (Mean +/- SD). Cardiac
      output, left ventricular systolic pressure and mean arterial pressure during CPR
      were nearly identical in both groups. The first hour of restored spontaneous
      circulation in group B was characterised by a significantly increased heart rate
      combined with significantly lower values for cardiac inotropy, cardiac output,
      left ventricular systolic pressure and mean arterial pressure. It is concluded
      that in acute or short-term cardiac arrest the currently recommended epinephrine
      dosages are sufficient. Higher doses of epinephrine for CPR seem to be
      recommendable only after prolonged cardiac arrest and/or during prolonged
      resuscitation.

PMID- 1391365
TI  - [Intubation aid by a rigid endoscope].
AB  - A method has been developed making it possible to look around intubation
      obstacles with the aid of rigid angular-lens systems. A glottis that is not or is
      only partly visible in direct laryngoscopy can be visualized endoscopically. The
      normal intubation technique is retained. A rigid endoscope is additionally
      introduced into the oropharynx, the glottis located endoscopically, and the
      endoscope secured to the laryngoscope in the position. The free hand can then be
      used to advance the tube through the glottis into the trachea under endoscopic
      control. This endoscopic method is intended to augment the physician's
      instrumental repertoire.

PMID- 1391366
TI  - [Initial experiences with rigid angled optical systems as intubation aids in
      difficult intubation].
AB  - Referring to a classification by Cormack, difficult laryngoscopy of Grade 3 (only
      the epiglottis or a part of it can be seen) was simulated in 16 patients by
      lowering the blade of the laryngoscope, so that the epiglottis was pushed down
      and thus covered up the vocal cords. The object of the study was to test whether
      a newly developed rigid endoscope is a useful tool during intubation in cases of
      laryngoscopical view Grade 3. After simulation of Grade 3 as mentioned above,
      using a clip, an angle optic was fixed to the vertical part of the blade, so that
      the movement of the optic in the sagittal level was still possible. If an
      improvement of the laryngoscopical view was possible, the tracheal tube was
      inserted via the nasal route until the top of the tube could be seen in the
      oropharynx. The tracheal tube was inserted into the trachea, under endoscopic
      control. With this new method, naso-tracheal intubation under endoscopic control
      in all 16 patients was successful, without affecting the pharynx and the vocal
      cords.

PMID- 1391367
TI  - [Curare and its successors. A 50-year's evolution].
AB  - The introduction of curare into clinical anaesthesia by Griffith and Johnson in
      1942 contributed to the termination of the era where anaesthesia was a reversible
      intoxication rather than the result of controlled drug action. Curare allowed
      general anaesthesia to be reduced to a lighter level, thereby conferring a
      significant safety factor to the patient. Both the shortage in supply of crude
      curare and its variable composition led the search for synthetic curare analogues
      conferring well defined pharmacodynamic and pharmacokinetic properties. Based on
      the chemical structure of tubocurarine which has been known since 1935 the
      efforts concentrated on bisquaternary ammonium compounds. Gallamine was the only
      synthetic curare analogue to contain three quaternary ammonium groups. This drug
      had significant undesired vagolytic effects. In 1951 succinylbischoline appeared
      to be the ideal muscle relaxant, particularly with respect to its fast onset and
      short duration of action. The disadvantages of its depolarising mechanism of
      action which were appreciated during the years to follow prevented the concept of
      depolarising neuromuscular blockade to be pursued further. With other muscle
      relaxants, including curare itself, histamine release, vagal blockade and
      ganglionic blockade were undesired effects to be eliminated in future compounds.
      Improved understanding of structure-activity relationships turned out to be an
      indispensable tool for future research. This in turn required more elaborate
      methods in chemical analysis, in electrophysiology of the motor endplate, and in
      ultrastructural research. As a result, alcuronium and pancuronium became
      available in the late sixties and early seventies. Both muscle relaxants had a
      non-depolarising mechanism of action with reduced side effects relative to
      curare. From now on better techniques for pharmacodynamic and pharmacokinetic
      research became available resulting in research activity with particular emphasis
      in this field. Researchers became aware that new muscle relaxants should be
      designed for larger volumes of distribution and more rapid biodegradation than
      those currently available. Concurrently, anaesthesia techniques had changed in a
      way to use intubation and mechanical ventilation as a routine procedure. The risk
      of intraoperative hypoventilation and hypoxemia was eliminated, yet, due to the
      lack of adequate monitoring techniques the slow recovery from curare, alcuronium
      or pancuronium neuromuscular blockade was hardly appreciated.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1391368
TI  - [Respiratory therapy for prevention of postoperative respiratory insufficiency].

PMID- 1391369
TI  - [Acute respiratory distress in adults].

PMID- 1391370
TI  - [ARDS: possible role of bacterial exotoxin].

PMID- 1391371
TI  - [Differential ventilation in respiratory insufficiency].

PMID- 1391373
TI  - [Treatment with phosphodiesterase inhibitors: Contra].

PMID- 1391372
TI  - [Treatment with phosphodiesterase inhibitors: Pro].

PMID- 1391374
TI  - [Spontaneous bacterial peritonitis without ascites].
AB  - A 34-year-old woman with acute pain in the lower abdomen and a history of non-A
      non-B-hepatitis underwent laparotomy. A diffuse light redness of the small bowel
      without ascites was the only abnormal finding. An appendectomy was performed. The
      patient deteriorated into a sepsis during the next 60 hours. Relaparotomy
      established acute diffuse peritonitis with ascites and without any apparent intra
      abdominal source of infection. Tracheal, blood, and intraperitoneal cultures of
      both procedures grew group A streptococci and proved a haematogenous spread of
      the infection. The sepsis was successfully treated with antibiotics and
      peritoneal lavage. The course of the infection and the findings are discussed and
      the case is interpreted as a spontaneous bacterial peritonitis without ascites.

PMID- 1391375
TI  - Alcohol and other drug abuse: changing lives through research and treatment.

PMID- 1391376
TI  - The relationship between sexual addiction and sexual dysfunction.

PMID- 1391377
TI  - The New Mexico Treatment Outcome Study: evaluating the utility of existing
      information systems.

PMID- 1391378
TI  - Boarder babies and drug-exposed children in the nation's capital.

PMID- 1391379
TI  - Substance use by homeless pregnant mothers.

PMID- 1391380
TI  - Serial, parallel, and integrated models of dual-diagnosis treatment.

PMID- 1391381
TI  - Developing positive self-concepts and assertive leadership.

PMID- 1391382
TI  - A paradigm for socialization: empowering African-American substance abusers to
      maximize their human potential.

PMID- 1391383
TI  - Making a difference through prevention and treatment.

PMID- 1391384
TI  - The challenge of dual diagnosis.

PMID- 1391385
TI  - The national impact of alcohol and drug problems and HIV infection and AIDS among
      the poor and underserved.

PMID- 1391386
TI  - The most deadly of all sins....

PMID- 1391387
TI  - Madness and addiction: treating the mentally ill chemical abuser.

PMID- 1391388
TI  - Sociodemographic factors in drug abuse treatment.

PMID- 1391389
TI  - Comorbidity of mental and addictive disorders.

PMID- 1391391
TI  - Hormone replacement therapy in post-menopausal women.

PMID- 1391390
TI  - Society, drug injectors, and AIDS.

PMID- 1391392
TI  - Breast cancer risk and the administration of human hormones. Part I. Hormone
      replacement therapy.

PMID- 1391393
TI  - Adverse effects of antiarrhythmic drugs.

PMID- 1391394
TI  - Immune response in biocompatibility.
AB  - Biocompatibility is concerned with the interactions that occur between
      biomaterials and host tissues. As foreign objects in that host tissue these
      materials may initiate several types of response. It has often been postulated
      that the immune response, by which the host normally defends itself against
      invasion by foreign organisms, can be involved in the response to biomaterials.
      This review discusses the mechanisms by which this could occur and the evidence
      that suggests the immune response is indeed of significance in biocompatibility.

PMID- 1391395
TI  - Preparation and characterization of Al2O3 reinforced hydroxyapatite.
AB  - The microstructure of Al2O3 reinforced hydroxyapatite (HA-Ca5(PO4)3OH) was
      studied. It was demonstrated that in this composite the Al2O3 particles are
      uniformly distributed in a matrix of spherical HA agglomerates formed by primary
      needlelike HA particles present before making green compact. In the HA + 20 wt%
      Al2O3 system, hydroxyapatite is partially decomposed into alpha-Ca3(PO4)2 and CaO
      with H2O vapour during sintering. Subsequently, the CaO is combined with Al2O3 to
      produce calcium aluminates (CaAl2O4 and CaAl4O7).

PMID- 1391396
TI  - Heterogeneous synthesis of fluoridated hydroxyapatites.
AB  - Fluoridated hydroxyapatites were synthesized with two different modes of fluoride
      supply: by supplying F(-)-free solution initially, followed by a F(-)-containing
      solution whose fluoride concentration was stoichiometrically equal to that of
      fluorapatite; and with the order of supply of these solutions reversed. Both of
      these heterogeneously synthesized fluoridated hydroxyapatites showed typical
      calcium phosphate X-ray diffraction patterns; and both had similar total fluoride
      contents (0.94 +/- 0.02 and 0.99 +/- 0.03 mmol/g, respectively), i.e. half of the
      maximum fluoride content of fluorapatite. However, they differed considerably in
      their physico-chemical properties. The former had a wider peak breadth of X-ray
      diffraction and a lower apparent solubility (Ca = 12.2 +/- 0.7 mmol/l) than the
      latter (Ca = 19.8 +/- 0.4 mmol/l) at 37 degrees C and pH 4.0. Wavelength
      dispersive spectroscopy attached to scanning electron microscopy gave clearly
      different spectra. Electron spectroscopy for chemical analysis of apatite pellets
      made by pressing and heating showed a slightly larger F1s signal at the crystal
      surface of the former, although the difference was not marked. These results
      suggest that two different types of heterogeneous fluoridated hydroxyapatites
      were formed, hydroxyapatite covered with fluorapatite and fluorapatite covered
      with hydroxyapatite.

PMID- 1391397
TI  - Experimental study on osteoconductive properties of a chitosan-bonded
      hydroxyapatite self-hardening paste.
AB  - A developmental bone substitute, composed of a chitosan-bonded hydroxyapatite
      paste and having various possible applications in medical and dental treatments,
      was evaluated with regard to its osteoconductive properties. Radiographic
      examination revealed that a bone-like irregular radiopacity appeared in the
      region of the embedded paste. This was judged histopathologically as the
      formation of bone tissue with chondral tissue. These data suggest that the paste
      has osteoconductive properties, and may, therefore, prove clinically useful as a
      bioactive bone substitute.

PMID- 1391398
TI  - Epicardial propranolol administration for ventricular arrhythmias in dogs: matrix
      formulation and characterization.
AB  - The effect of propranolol on the prevention of ventricular
      tachycardia/fibrillation (VT/VF) due to acute coronary ischaemia was studied in
      dogs. A series of propranolol-polymer controlled release matrices in slab
      configuration using various polyurethanes and a polyurethane-silicone rubber
      copolymer were formulated and characterized. In general, drug release in vitro
      occurred with an initial burst phase followed by an exponentially declining
      delivery rate; the silicone rubber containing copolymer preparation had more
      sustained release properties than did pure polyurethane matrices. In the animal
      studies, dogs underwent 5-hourly 10 min complete occlusions of the left anterior
      descending coronary artery (LAD), followed by 50 min normal perfusion. During non
      drug occlusions VT occurred at a frequency of 1.22 +/- 0.12 episodes/min. A
      propranolol-polyurethane matrix (30% w/w, 28-42 mg) was placed on the ischaemic
      zone of the left ventricular epicardium immediately after the fifth occlusion.
      After an hour of drug delivery a sixth occlusion took place. The number of
      arrhythmia episodes both before and after drug were quantified and compared. The
      time to ventricular fibrillation (when present) and the mean blood pressure were
      also assessed. The drug patch delivered propranolol at a dose of 140 +/- 45
      micrograms/kg by the conclusion of the 1 h study period. Therapeutic drug levels
      were achieved in the peripheral blood samples (8.7-43.7 ng/ml) and were enhanced
      in coronary venous samples (360.9-556.2 ng/ml). Reduction of blood pressure and
      proarrhythmic events following epicardial controlled release propranolol
      administration were noted but were not statistically significant. Arrhythmia
      episodes before and after propranolol were not found to be significantly
      different (VT/min 1.02 +/- 0.31 and 1.22 +/- 0.12).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391399
TI  - Stability constants of Ca-alkyl salicylate complexes and their effect on the
      dissolution of calcium hydroxide dental cements.
AB  - The proton-ligand stability constants (pKa) and Ca-ligand stability constants
      (log beta) of the five types of alkyl salicylate were determined and the
      dissolution of the calcium hydroxide cements prepared from those salicylates was
      examined in water. The dissolution of the cements containing monoesters decreased
      with the increase in their pKa and log beta values. The cement containing diester
      showed lower dissolution than that estimated from those values. This seems to be
      related to the polymeric structure of the cement matrix consisting of the complex
      of the diester with calcium.

PMID- 1391400
TI  - Analysis of surface cleanliness of three commercial dental implants.
AB  - Six routinely packaged commercially pure titanium dental implants (three
      commercial brands) were analysed using secondary ion mass spectrometry to examine
      the outermost surface layer. The aim of the analysis was to compare the surface
      purity (99.95%) of the implants with the substrate metal, common to all three
      brands. The use of a low primary ion current density provided a nominal
      protection limit of 0.01% or 100 p.p.m. All the implants examined had extremely
      pure surfaces. However, only one brand of implant had an ultraclean oxide surface
      in relation to the substrate.

PMID- 1391401
TI  - Joint replacement components made of hot-forged and surface-treated Ti-6Al-7Nb
      alloy.
AB  - We have developed a titanium-aluminium alloy with the inert alloying element
      niobium. The optimal composition was found to be Ti-6Al-7Nb (Protasul-100). This
      custom-made alloy designed for implants shows the same alpha/beta structure as Ti
      6Al-4V and exhibits equally good mechanical properties. The corrosion resistance
      of Ti-6Al-7Nb in sodium chloride solution is equivalent to that of pure titanium
      and Ti-6Al-4V. This is due to a very dense and stable passive layer. Highly
      stressed anchorage stems of different hip prosthesis designs have been made from
      hot-forged Ti-6Al-7Nb. The polished surfaces of hip, knee and wrist joints made
      of Ti-6Al-7Nb and articulating against polyethylene are surface-treated by means
      of a very hard and 3-5 microns thick titanium nitride coating (Tribosul-TiN) or
      by oxygen diffusion hardening (Tribosul-ODH) to a depth of 30 microns.

PMID- 1391402
TI  - Studies on immobilization of urease in gelatin by cross-linking.
AB  - Urease enzyme was immobilized in photographic gelatin by chemical cross-linking
      using formaldehyde, glutaraldehyde and chromium (III) acetate. The effects of
      enzyme and cross-linker concentrations, temperature, incubation time and pH on
      urea hydrolysis were investigated. Effect of reuse on the activity of immobilized
      enzyme was also studied. Glutaraldehyde (0.004 M) was the most suitable cross
      linker; relative activities within 2.5 months after 24 reuses were stable (about
      78%).

PMID- 1391403
TI  - ESCA investigation of low-temperature ammonia plasma-treated polyethylene
      substrate for immobilization of protein.
AB  - A low-temperature radiofrequency plasma excited in anhydrous ammonia was used to
      modify polyethylene substrate surfaces for covalent immobilization of proteins.
      Electron spectroscopy for chemical application (ESCA) was used for surface
      characterization of polyethylene to a depth scale of 7 nm. The data revealed that
      surface modification is extensive and occurs in seconds at low discharge power.
      Primary amino functionalities were detected on the polyethylene surface and the
      level is dependent on plasma parameters. 125I-labelled antibodies covalently
      attached to amino groups via glutaraldehyde allowed the conditions for optimum
      level of primary amine to be established. Both ESCA data and protein loadings are
      in excellent agreement.

PMID- 1391404
TI  - Sticking coefficients of adsorbing proteins.
AB  - The protein sticking coefficient, phi, the fraction of collisions that result in
      adsorption, is a function of the molecular interactions between the protein and
      the surface. A random walk and diffusion-to-capture model was used to describe
      the kinetics of protein adsorption. The assumption of a constant sticking
      coefficient leads to a first-order model of the kinetics. A solution of the
      problem of adsorption from a semi-infinite medium with first-order kinetics at
      the boundary was obtained by numerical simulation on the computer. The results of
      the computer simulations match the time dependence observed experimentally. A
      correlation was developed to estimate phi from experimental data. phi has been
      found to be in the range 10(-5)-10(-8) for several protein adsorption kinetic
      studies reported in the literature.

PMID- 1391406
TI  - In vivo degradation of massive poly(alpha-hydroxy acids): validation of in vitro
      findings.
AB  - The degradation of various high-molecular-weight aliphatic polyesters derived
      from glycolic acid and/or lactic acid enantiomers was previously investigated in
      vitro. It was demonstrated that the bulk degradation mechanism proposed in the
      literature actually proceeds heterogeneously and proceeds faster in the centre
      than at the surface of large specimens. In order to compare them, similar
      compression-moulded specimens were implanted intramuscularly in the backs of
      rabbits, namely PLA50 (poly(DL-lactic acid)), PLA37.5GA25 (75% DL-lactide and 25%
      glycolide in the feed) and PLA75GA25 (75% L-lactide and 25% glycolide). These
      three intrinsically amorphous compounds exhibited faster central degradation.
      Furthermore, preferential degradation of glycolic acid units and induced
      crystallization of L-lactic acid enriched fragments were observed in the case of
      PLA75GA25. These findings are comparable to phenomena observed in vitro and are
      conclusively supported by the re-examination of some old in vivo results.
      Accordingly, data reported in this paper validate both the in vitro modelling and
      new understanding of the degradation of lactic acid/glycolic acid-based aliphatic
      polyesters reported previously.

PMID- 1391405
TI  - In vivo fragmentation of microporous polyurethane- and copolyesterether elastomer
      based vascular prostheses.
AB  - A previous study showed that microporous, compliant and (bio)degradable vascular
      prostheses prepared from a polyurethane/poly(L-lactic acid) mixture can function
      as a temporary scaffold for the regeneration of small-calibre arteries. In this
      study the mechanism of fragmentation of vascular prostheses made of polyurethane,
      copolyesterether and blends of either polyurethane or copolyesterether with
      polymers differing in biodegradability, crystallinity and glass transition
      temperature is investigated. Animal studies revealed that after 6 wk of
      implantation only the prostheses made of blends containing a second polymer which
      was non-elastic at 37 degrees C were fragmented extensively, whether the second
      polymer was (bio)degradable or not. It is concluded that fragmentation of the
      prostheses is mainly caused by alternating stresses induced by the arterial
      pulsations and that (bio)degradation plays a minor role.

PMID- 1391407
TI  - Biodegradable polymers. II. Degradation characteristics of hydrolysis-sensitive
      poly[(organo)phosphazenes].
AB  - Polyphosphazenes with hydrolytic labile substituents have potential as
      biodegradable materials. By proper choice of the substituents, polymers can be
      prepared which can degrade to harmless products. The rate of biodegradation and
      the nature of the degradation products can be widely varied by changing the
      chemical composition of the polymers. The degradation properties of a series of
      new polyphosphazene derivatives are discussed. The synthesis of phosphazene
      polymers with variable amounts of ethyl 2-(O-glycyl)lactate or ethyl 2-(O
      alanyl)lactate as cosubstituents was described previously. These polymers were
      prepared by partial reaction of poly[(dichloro)phosphazene] with the
      corresponding amine compound. Total halogen replacement was achieved by
      subsequent introduction of glycine ethyl ester cosubstituents. The degradation
      characteristics of these polymers in organic solution or in vitro was
      investigated. It was demonstrated that the introduction of hydrolysis-sensitive
      side-groups along the polymer chain results in an increased degradability of the
      poly[(amino acid ester)phosphazenes]. A plausible mechanism for the hydrolysis of
      these materials is proposed. The main hydrolysis pathway of poly[(amino acid
      ester)phosphazene] devices in vitro involves release of the amino acid ester side
      group followed by hydrolysis of the ester with formation of the amino acid and
      ethanol. Initial hydrolysis of the ester bond with subsequent release of glycine
      cannot be excluded but is probably predominant.

PMID- 1391409
TI  - Porous polymer implants for repair of full-thickness defects of articular
      cartilage: an experimental study in rabbit and dog.
AB  - Full-thickness defects of articular cartilage were repaired by implantation of
      porous polymer implants in rabbits and dogs. The quality of the repair tissue was
      determined by collagen typing with antibodies. Implants with varying pore sizes
      and chemical composition were used. The effect of loading and motion was
      determined by inserting implants higher than, level with and lower than the
      surrounding cartilage. It appeared that healing took place by formation of
      fibrocartilaginous repair tissue containing both type I and type II collagen.
      Hyaline cartilage was observed in a minority of the rabbits used but not in the
      dog. Fibrocartilage formation in the dog was simulated by implantation of a
      porous polymer. Chemical composition of the polymer did not alter the results,
      neither did loading of the implant. It is concluded that the formation of
      fibrocartilaginous repair cartilage is stimulated by implantation of a porous
      polymer. This tissue seemed to function adequately in the dog but did show signs
      of degeneration in the rabbit.

PMID- 1391408
TI  - Wettability of cross-linked collagenous biomaterials: in vitro study.
AB  - Collagenous biomaterials can be treated by chemical and physical agents to
      decrease biodegradation rate. Treatments to collagen may modify surface
      properties and subsequently cell and platelet behaviour. Collagenous films were
      either uncross-linked and cross-linked by glutaraldehyde, formaldehyde or
      cyanamide and/or treated by a severe dehydration. Contact angles, platelet
      contacting assay and fibroblast morphology were investigated. After severe
      dehydration, wettability was diminished except for formaldehyde-cross-linked and
      severely dehydrated films. Glutaraldehyde-cross-linked collagen results in an
      increase in wettability. Platelets were similarly distributed, except on
      formaldehyde-cross-linked films that exhibited no platelet aggregation.
      Fibroblasts were in a spreading phase on most collagenous films. However,
      cytotoxicity was noticed on some aldehyde-cross-linked films. No direct
      relationship was found between contact angles and platelet-cell attachment.

PMID- 1391410
TI  - Chitosan cross-linked with Mo(VI) polyoxyanions: a new gelling system.
AB  - A procedure for preparing homogeneous chitosan gels by in situ molybdate cross
      linking is described. The gels are obtained by dispersing solid MoO3 in a
      buffered chitosan solution and the polymer is cross-linked by formation of
      heavily negatively charged molybdate polyoxyanions. The resulting ionic gels are
      very transparent, thermoirreversible and can be made at low polymer
      concentrations. Depending on the ionic strength, these gels are able to swell
      several times their original size in aqueous solutions. Estimates of the degree
      of cross-linking reveal a very open pore structure which is confirmed by electron
      micrographs of the gel.

PMID- 1391411
TI  - Implantation of p(HEMA)-collagen composite into bone.
AB  - The replacement of bone defects is very important in clinical practice. This
      study compares biological properties of poly(2-hydroxyethyl methacrylate)
      collagen composite with those exhibited by pure p(HEMA), an insoluble fraction of
      calf skin collagen (ISC-40) and demineralized bone matrix after implantation into
      pig or dog femurs. The levels of biodegradation or destruction of implants and
      healing of bone defects were studied using X-ray photography, histology and
      enzyme histochemistry. The results indicated a significant effect of collagen on
      biological destruction of the p(HEMA)-composite implants; even a minute amount of
      collagen influences this process dramatically. A stimulatory action of collagen
      on new bone formation may be of importance in bone defect healing.

PMID- 1391412
TI  - Refractive index and molar refraction of methacrylate monomers and polymers.
AB  - The refractive indices of a number of methacrylate monomers have been measured
      and corresponding molar refraction data calculated. Similar determinations were
      made on a number of methacrylate polymers. The molar refraction values determined
      were in excellent agreement with the values calculated from the published molar
      refraction values of the chemical groups involved. There was little difference
      between the molar refraction values of monomers and that of the repeat unit in
      the corresponding polymers, in marked contrast to the molar volumes. The ratio of
      refractive index to molar volume was reasonably consistent for all methacrylates
      studied (0.25-0.30 approximately).

PMID- 1391413
TI  - Phagocytosis of carbon particles by macrophages in vitro.
AB  - Particles of known size ranges of carbon fibre-reinforced carbon were presented
      to in vitro cultures of murine macrophages. Particles of up to 20 microns
      diameter were phagocytosed. Larger particles were not phagocytosed but became
      surrounded by aggregations of macrophages, some of which migrated on to the
      particle surfaces. Mean rates of phagocytosis up to 2.5 particles per hour were
      observed. Cells presented with a large excess of particles became rounded,
      detached from the substrate and some underwent lysis. The implications of these
      findings for the fate of particulates released from implanted medical devices is
      discussed. It is argued that a mechanism exists where particles in the size range
      8-20 microns, released from medical devices, are small enough to be phagocytosed
      by macrophages and transported to the lymphatics and subsequently to the vascular
      circulation but large enough to lodge in capillary beds of tissues remote from
      the implant site.

PMID- 1391415
TI  - Autogenous and allogeneic bone grafts in periodontal therapy.
AB  - This article is limited to a review of bone autografts and allografts, as used in
      periodontal therapy. The various graft materials are discussed with respect to
      case reports, controlled clinical trials, and human histology. Other reviewed
      areas are wound healing with periodontal bone grafts, tissue banking and freeze
      dried bone allografts, and the use of bone grafts in guided tissue regeneration.

PMID- 1391414
TI  - Cystatins--inhibitors of cysteine proteinases.
AB  - The cystatin superfamily of proteins, derived from a common ancestor, is
      comprised of a diverse group of potent cysteine proteinase inhibitors and
      antibacterial/viral agents grouped into several families. This review
      concentrates on family 2 cystatins, namely, the human salivary cystatins and
      cystatin C. Emphasis is given to their physicochemical and functional properties
      at both the protein and the molecular level. The role of cystatins in disease
      processes, including those in the oral cavity, is also discussed. Finally, future
      directions for cystatin research in oral biology are presented.

PMID- 1391416
TI  - The cultured diploid fibroblast as a model for the study of cellular aging.
AB  - The limited proliferative potential of the cultured human diploid fibroblast is
      now well established. A number of biological correlates suggest that this culture
      system is a model for the study of aging at the cellular level. The mechanism(s)
      that causes the loss of proliferative activity is unknown; the results of some
      recent studies indicate that specific genes may play a pivotal role in cellular
      aging in vitro. The extent to which changes in proliferative functions are
      causally related to aging in vivo is currently under investigation.

PMID- 1391417
TI  - The sense of taste: neurobiology, aging, and medication effects.
AB  - The sense of taste is an oral chemical sense in mammals that is involved in the
      choice of foods. Initial transduction of taste stimuli occurs in taste buds,
      which are distributed in four discrete fields in the oral cavity. Medications can
      affect the taste buds and ion channels in taste-bud cell membranes involved in
      stimulus transduction. The sense of taste gradually declines with aging, with
      bitter taste most affected. Neural circuits that mediate taste in primates
      include cranial nerves VII, IX, and X, the solitary nucleus in the brain stem,
      the ventroposteromedial nucleus of the thalamus, and the insular-opercular
      cortex. The central taste pathways process taste information about sweet, salty,
      sour, and bitter stimuli serially and in parallel. Medications associated with
      "metallic" dysgeusia and taste losses affect the taste system via unknown
      mechanisms.

PMID- 1391418
TI  - Some aspects of perfluorochemical emulsion's interaction with blood.
AB  - FDC/FTPA (7:3) emulsions stabilized by procsanol (Emulsion 1) and by procsanol
      with yolk phospholipids (Emulsion 2) were incubated with the donor plasma. After
      the incubation during 6 hours of Emulsions 1 and 2 with plasma the 36% and 50%
      decrease of the cholesterol content in plasma was found. Analysis of the lipid
      content of lipoproteins after the Emulsion 2 administration to rats (2.5 ml/100 g
      of weight) revealed the 50% decrease of the cholesterol amount in the HDL
      fraction at 3 and 24 hours posttransfusion. The ratio cholesterol/total
      phospholipids in the erythrocyte membrane diminished up to 50% as well. The equal
      degree of the cholesterol adsorption by emulsion from plasma, HDL of rats and
      erythrocyte membrane is an evidence of nonspecific interaction of PFC particles
      with the blood components containing cholesterol.

PMID- 1391419
TI  - Studies on blood substitutes based on hemoglobin and perfluorocarbon.
AB  - Unmodified, and to a lesser extent, modified stroma-free hemoglobin preparations
      have been reported to exhibit coronary and renal vasoconstrictor activity in
      isolated perfused hearts and kidneys. The physiological significance in vivo of
      such ex vivo demonstrated vasoconstriction has not yet been established. We have
      conducted a number of in vivo dog experiments designed to elucidate (a) whether
      free hemoglobin in the plasma phase contributes to diffusive oxygen supply to the
      tissues and (b) whether excessive vasoconstriction results in functional
      impairment. Our findings indicate that (a) the infusion of unmodified SFHS does
      not cause a significant disturbance of central hemodynamics, although it causes
      an elevation of the arterial blood pressure; the latter is accompanied by
      vasoconstriction in the skeletal muscle vascular bed and in the renal cortex; (b)
      there is no significant improvement of diffusive oxygen supply to the tissue at
      rest; and (c) that glutaraldehyde cross-linked SFHS administered to hypotensive
      dogs causes a brief further aggravation of hypotension as well as renal
      vasoconstriction accompanied by renal functional impairment. The findings suggest
      that coronary autoregulatory mechanisms in vivo can override the vasoconstrictor
      potency demonstrated in vitro, but the renal effects of SFHS containing
      unmodified hemoglobin can give rise to significant concern.

PMID- 1391420
TI  - Blood substitutes made on the basis of perfluorocarbons inhibit intracellular
      energy generation.
AB  - Although perfluorocarbons (PFC) are chemically inert, toxic reactions are
      observed on using them as fluorocarbon emulsions in blood substitutes. Six to
      twelve hours after exchanging about half of the circulating blood of conscious
      rats pathobiochemical reactions occur despite a high interarterial oxygen
      pressure. They indicate the disturbance of intracellular energy generation, which
      is characterized by a decrease in ATP, increase in ADP, inorganic phosphate and
      potassium, increase in NADH and lactate. Impurities of perfluorocarbons and
      effects of the surfactant were excluded to be causes of this disturbance. The
      following hypotheses were proposed: Storing of perfluorocarbons in the
      mitochondrial membrane decreases the ATP-forming proton gradient on the membrane
      and the electron transport in cytochromes is disturbed, respectively.

PMID- 1391421
TI  - Perfluoroalkylated surfactants: relationships between structure and acute
      toxicity in mice.
AB  - New single chain neutral, and single and double chain zwitterionic
      perfluoroalkylated surfactants or co-surfactants have been evaluated for in vivo
      applications. A study of the relationship between structure and acute toxicity in
      mice is presented. Acute toxicity evaluations i.v. in mice indicate the following
      trends (increasing tolerance): zwitterionic single-chain less than neutral single
      chain less than zwitterionic double-chain and, where the polar head is concerned,
      single-chain compounds: phosphocholine less than phosphoramidate less than
      trehalose approximately sucrose less than maltose less than xylitol.

PMID- 1391422
TI  - Retention of perfluorochemicals in rat liver and spleen.
AB  - The uptake and retention of perfluorochemicals (PFCs) into rat liver and spleen
      have been measured for up to 28 d following injection of either the commercial
      PFC emulsion, Fluosol, or a novel perfluorodecalin (FDC)-based emulsion. Both
      quantitative and qualitative differences in the retention of individual PFCs were
      observed, depending on composition of emulsion administered. Nevertheless, uptake
      of PFCs into the spleen was consistently greater than into the liver,
      irrespective of formulation injected.

PMID- 1391423
TI  - Lymphoid tissue responses to concentrated perfluorochemical emulsions in rats.
AB  - The effects of injecting perfluorochemical (PFC) emulsions of varying
      concentrations on lymphoid tissues have been studied in rats. Tissue weights were
      increased in proportion with quantity of PFC injected, with spleen responses
      consistently greater than those of the liver. PFC droplets recovered from tissues
      had mean diameters in the 1-10 microns range, with those from the spleen being
      larger than from the liver. Recovered droplet diameters were considerably greater
      than freshly-prepared emulsion mean particle sizes (0.20-0.25 microns). This
      suggests that coalescence of emulsion droplets following accumulation in tissues
      is a pre-requisite to the eventual excretion of PFC vapour through the lungs.

PMID- 1391424
TI  - Acute effects of moderate Fluosol-DA hemodilution on hepatic microsomal and
      nonmicrosomal metabolism in rats.
AB  - Fluosol has been shown to alter the disposition of several drugs immediately
      after its administration. Investigations in this laboratory established that the
      disposition of several drug markers requiring the hepatic microsomal cytochrome P
      450 isoenzymes was time dependent for 72 hours. It was an additional purpose of
      the research to determine if the nonmicrosomal sulfation and acetylation pathways
      were also influenced by Fluosol hemodilution in a time dependent manner. Rats
      were moderately hemodiluted with Fluosol and received an intravenous dose of a
      drug marker 24, 48, or 72 hours after hemodilution. The formation clearance (ClF)
      of specific metabolites was used as the pharmacokinetic measure of a specific
      enzymatic activity. 3-Hydroxymethyl antipyrine ClF (phenobarbital inducible
      microsomal cytochrome P-450 isoenzymes) increased 300% only at 48 hours.
      Acetylsulfamethazine ClF (nonmicrosomal acetylation) increased 287% and 162% at
      24 and 48 hours, respectively. Acetaminophen sulfate ClF (nonmicrosomal
      sulfation) decreased 30% only at 48 hours. Substantial evidence shows that
      cytochrome P-450 content is induced at 72 hours and remains induced for an
      unprecedented length of time by the PFCs in Fluosol. Therefore, it was unexpected
      that 3-hydroxymethyl antipyrine ClF was not increased at 72 hours. Several
      possible explanations are discussed for the unexpected findings.

PMID- 1391425
TI  - Effect of a high concentration perfluorocarbon emulsion on platelet function.
AB  - Perfluorocarbon (PFC) and lipid emulsions (eg. Fluosol, Intralipid,) containing
      phospholipid have been reported to modify platelet function after intravenous
      infusion. Platelet activation might be responsible for the generation of
      mediators responsible for PFC-induced side effects. In view of this, we
      investigated the effect of a highly concentrated perfluorocarbon emulsion
      containing 90% (w/v) perfluorooctylbromide (perflubron; PFOB), on porcine and
      human platelet activation and function. We measured both: a) stimulated ex-vivo
      porcine platelet aggregation pre and post infusion of either perflubron or
      control (vehicle only) emulsions, and b) stimulated in vitro human platelet
      calcium flux in the presence of perflubron emulsion or control emulsions.
      Platelet aggregation stimulated by collagen, ADP or arachidonic acid (AA) was
      inhibited in ex-vivo porcine platelets following infusion of perflubron emulsion
      at a dose of 3 ml/kg (0.2 ml/kg/min). Inhibition was dose dependent and was
      decreased when the dose of perflubron emulsion was reduced to 1.0 or 0.3 ml/kg.
      Infusion of saline or "vehicle" emulsions had little or no effect on stimulated
      ex-vivo pig platelet aggregation. Fluosol, infusion was associated with
      inconsistent inhibition of platelet aggregation. A23187- or AA-stimulated calcium
      flux of human platelets in vitro was inhibited in the presence of 1% (v/v)
      perflubron emulsion. Similar effects were seen with Fluosol, or Intralipid. This
      inhibition was agonist dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391426
TI  - Prolonged shelf stability and biocompatibility of a concentrated injectable
      fluorocarbon emulsion.
AB  - A four-year-old 100% w/v concentrated emulsion of perfluorooctylbromide (PFOB,
      perflubron) stored at 5 degrees C, when submitted to the close-to-total exchange
      perfusion test in conscious rats (Hct 3-5%) still resulted in 75% survival.
      Particle size and size distribution, viscosity, pH were still in the acceptable
      range.

PMID- 1391427
TI  - Complete blood substitution during profound hypothermic cardiac arrest in dogs.
AB  - This study compared the effects of 3 hours of cardiac arrest performed at 2
      different levels of profound hypothermia in totally exsanguinated, blood
      substituted dogs. Dogs (N = 10) were anesthetized and esophageal temperature was
      lowered to 24 degrees at which time exsanguination began. Once exsanguination was
      complete and the heart had arrested, continuous whole body perfusion of an
      oxygenated blood substitute solution was performed for 3 hours. Core temperature
      during this period remained below 10 degrees C and reached nadirs of 1.3 degrees
      C in Group 1 (N = 5) versus 7.3 degrees C in Group II (N = 5). Once the dog was
      allowed to rewarm to 10 degrees C replacement of the perfusate with blood was
      begun. All dogs survived the procedure but 2 dogs from each group died by 4 days
      following the experiment. The remaining 6 dogs were observed for between 10 and
      85 days. The group perfused with blood substitute at the warmer nadir had a
      faster recovery of motor behavior and showed smaller changes from normal in
      several biochemical and hematological parameters. These findings indicate that
      profound hypothermia and total blood substitution can be successfully achieved at
      either temperature nadir, but the warmer level appears to be associated with a
      faster recovery.

PMID- 1391428
TI  - Fluosol DA-20% in treatment of severe anemia: ongoing studies in 52 patients.

PMID- 1391429
TI  - Arterial blood gases and brain oxygen availability following infusion of
      intratracheal fluorocarbon neat liquids.
AB  - Eight adult New Zealand Swiss rabbits (3-5 kg) having previously implanted
      chronic bilateral platinum electrodes in the visual cerebral cortex and
      subcutaneous silver reference electrodes were tranquilized and monitored in
      multiple 2-3 hour sessions using voltammetric techniques. Six of these were given
      intratracheal neat liquid fluorocarbons ranging in boiling point from 132 degrees
      C to 215 degrees C at doses of 2 or 4cc/kg. Each animal received only one
      fluorocarbon liquid. Two additional rabbits were match-studied as controls. Half
      of the rabbits have survived more than five months. Both controls and two
      experimental rabbits were sacrificed after more than seven months due to gastric
      hairballs. The period of daytime monitoring sessions, when cathodic brain oxygen
      currents (aO2), arterial blood gases and pH were obtained, was between 34 and 263
      days. In some animals the arterial pCO2 was increased during the first week but
      the pO2 and pH remained nearly normal in all eight animals throughout. The two
      best fluorocarbons for liquid breathing on the basis of this limited but
      intensive work are F-methyldecalin and F-5,6H-dec-5-ene (F44E).

PMID- 1391430
TI  - Response of the rabbit lung as a criterion of safety for fluorocarbon breathing
      and blood substitutes.
AB  - From the first liquid breathing experiments until now, the lung, not
      surprisingly, has played a central role in the evolution of fluorocarbon blood
      substitutes. The first breathable fluorocarbon, a mixture of F-alkylfurans(FC75),
      bp 102 degrees C, while a poor solvent for the lung's lining and a good solvent
      for oxygen and carbon dioxide, proved to cause a characteristic gas/vapor
      microbubble embolism following intravenous administration as an emulsion. Higher
      boiling fluorocarbons, e.g. F-tributylamine (FC47), bp 174 degrees C, do not
      produce such gas-vapor emboli. However, intermediate boiling compounds such as F
      decalin (PP5), bp 141 degrees C, produce lungs which, although they certainly
      appear not to contain microbubble emboli, do not collapse when the thorax is
      opened. Such hyperinflated non-collapsible lungs (HNCL) occur in the rabbit after
      the intravenous infusion of F-decalin emulsions as well as after the
      intratracheal infusion of F-decalin neat liquid. F-decalin induced HNCL retain
      their appearance and low specific gravity for many weeks, gradually returning
      toward normal after many months. F-methyl decalin, bp 165 degrees C, does not
      cause HNCL after intravascular or intratracheal administration. Fluorocarbons
      having boiling points between 140 degrees C and 165 degrees C are being tested in
      order to find a perfluorinate with the highest transpiration rate, and hence
      vapor pressure, compatible with an acceptable body dwell time. We have given
      fluorocarbons intratracheally to 75, intravenously to 221 and both
      intratracheally and intravenously to 8 rabbits. Free radical trapping agents,
      antineutrophil, antiinflammatory and other drugs have been administered without
      appreciable decrease of HNCL. Fluorocarbon critical solution temperature, lipid
      solubility, emulsifiability, and other physicochemical properties may mediate the
      pulmonary effect. One method of preventing and treating low dose F-decalin
      induced HNCL in rabbits is described.

PMID- 1391431
TI  - Microsphere encapsulated l-ascorbic acid: its effects on erythrocytes during 56
      days storage.

PMID- 1391432
TI  - Biological effects of photoactivated-HPD and cholesteryl hemisuccinate on
      erythroid differentiation.
AB  - In order to establish the ability of porphyrins to distinguish between
      differentiated and undifferentiated cells of the erythropoietic pathway, the
      cytotoxic effects of hematoporphyrin derivative (HPD) on Friend erythroleukemic
      cells (FLC) were derivative (HPD) on Friend erythroleukemic cells (FLC) were
      studied. Since cholesterol affects the fluidity of cell membranes, the inhibitory
      effect of cholesteryl hemisuccinate (CHS) on HPD was similarly tested. FLC were
      induced with either dimethyl sulfoxide (DMSO), hemin, or both. The cells
      responded to DMSO-treatment by the synthesis of a large amount of hemoglobin and
      a decrease in both the cell volume and rate of cell-growth. Hemin, on the other
      hand, did not drive FLC to synthesize hemoglobin and reduced only moderately the
      growth rate compared to untreated cultures. The combined effect of DMSO and hemin
      led to a profound inhibition of the growth rate, but did not increase the
      synthesis of hemoglobin compared to the level observed in cells treated with DMSO
      only. The binding property of HPD to FLC was also determined. DMSO-treatment
      significantly reduced the amount of HPD-binding, and combined treatment with DMSO
      and hemin resulted in even a lower level of HPD-binding. On the other hand,
      induced as well as non-induced cells showed the same sensitivity to
      photoactivated HPD when both DNA and protein synthesis were examined.
      Pretreatment of both differentiated and undifferentiated cells with CHS reduced
      the cytotoxicity of photoactivated HPD to the same level. We conclude that the
      decreased binding of HPD to differentiated cells is a result of a reduction in
      their cell volume. Thus, the differentiation process per se does not protect
      cells against the photodynamic effect of HPD. Moreover, CHS may act as a
      scavenger or first acceptor of singlet oxygen blocking the photodynamic effect.

PMID- 1391433
TI  - Blood substitutes based on modified hemoglobin prepared by encapsulation or
      crosslinking: an overview.
AB  - Modified hemoglobin consists of (1) encapsulated hemoglobin and (2) crosslinked
      hemoglobin (polyhemoglobin, intramolecularly cross-linked hemoglobin and
      conjugated hemoglobin). There have been new advances in all types of modified
      hemoglobins. Modified hemoglobins are effective in hemorrhagic shock. However, it
      is important to define hemorrhagic shock models and experimental designs.
      Important progress has been made in research on vasoactivities, organ perfusion,
      organ preservation, biodistribution, hematology, complement activation immunology
      and other areas. A preclinical screening test may bridge the gap between animal
      safety studies and injection into human. Potential new sources of hemoglobin
      included bovine hemoglobin, recombinant human hemoglobin and synthetic heme.

PMID- 1391435
TI  - Potential clinical applications for blood substitutes.
AB  - In the coming decade, it is likely that oxygen-carrying alternatives to red blood
      cells will become available for clinical use. The driving force behind their
      development is the risk of transfusion of homologous blood, which includes
      transmission of viral disease (HIV and hepatitis) and transfusion reactions as
      well as the expense of collecting and storing human blood. A number of clinical
      applications for these products can be anticipated now, but when available, it is
      likely that the list will grow. How widely these products will be used depends on
      their safety. In addition to these clinical applications, blood substitutes will
      be useful in furthering our understanding of basic oxygen transport physiology.

PMID- 1391434
TI  - Overview of progress in the fluorocarbon approach to in vivo oxygen delivery.
AB  - The development of fluorocarbon-based oxygen carriers has experienced rapid
      progress over the past few years. Fluosol has been approved for use during
      percutaneous transluminal coronary angioplasty (PTCA) for high-risk patients. Its
      clinical evaluation is being pursued as an adjunct to cancer therapy and for
      treatment of myocardial infarction in conjunction with thrombolytic therapy. O2
      delivery efficacy has been achieved with the development of the new highly
      concentrated (4 to 5 times more concentrated than Fluosol), fluid, emulsions of
      perfluorooctyl bromide (perflubron), trade-named Oxygen. The stability of
      fluorocarbon emulsions has also improved considerably and the new emulsions can
      be stored unfrozen and are ready for use. The side-effect profile of these
      emulsions has been characterized as being the normal response of the body's
      phagocytes to the injection of particles, a response that is considered
      physiological rather than pathological in nature; it involves some products of
      arachidonic acid metabolism and can be controlled pharmacologically. Means of
      further stabilizing fluorocarbon emulsions, involving molecular-diffusion
      controlling additives or fluorinated surfactants, including mixed fluorocarbon
      hydrocarbon compounds, have been devised. Increased control over in vivo particle
      recognition, intravascular persistence and side effects, and at adapting emulsion
      characteristics to specific applications, is being investigated. The range of
      therapeutic applications is expanding. The concentrated emulsions will be able to
      serve as a temporary red blood cell substitute in many situations. Acute
      normovolemic hemodilution with fluorocarbon emulsions, used in conjunction with
      homologous predonation and other blood-sparing techniques, should afford greater
      flexibility, increase the margin of safety, and reduce or alleviate the need for
      autologous blood transfusion during surgical procedures. Fluorocarbon
      applications in the cardiovascular field include use during PTCA, for
      cardioplegia and reperfusion, and the treatment of myocardial infarction.
      Significant tumor growth delay has been achieved when concentrated emulsions are
      used in conjunction with cancer radio- or chemotherapy. Liquid ventilation has
      potential as a unique treatment for the adult and infant respiratory distress
      syndromes and for drug delivery. The radiopaque and versatile perflubron can also
      be used in contrast agents for diagnosis with computed X-ray tomography, magnetic
      resonance imaging and ultrasound, allowing the early detection and staging of
      cancer. Other potential applications investigated include the treatment of
      cerebral ischemia, organ and limb preservation, use as a tamponade during retinal
      repair, etc.

PMID- 1391436
TI  - Potential clinical applications of the oxygen carrying solutions.
AB  - Two major areas of research of the oxygen carrying solutions are 1) utilization
      of hemoglobin and 2) perfluorochemicals. Even though they are not perfect red
      blood cell substitutes, the "oxygen carrying solutions" have many potential
      clinical applications because they will reach tissues more easily than normal
      human red cells and can deliver oxygen directly to tissues. In this paper,
      important examples of such usages are suggested. Additional clinical and non
      clinical applications of the oxygen carrying solutions may be added in the near
      future.

PMID- 1391437
TI  - Preparation and characterization of crosslinked and polymerized hemoglobin
      solutions.
AB  - In 1982 we synthesized 2-Nor-2-formylpyridoxal 5'-phosphate (NFPLP) and
      subsequently showed that coupling of the beta chains of hemoglobin (Hb) by this
      organic phosphate compound according to Benesch et al. (1) lowers the oxygen
      affinity and prolongs the retention time in the circulation of rats and rabbits
      with a factor 3 by prevention of excretion via the kidneys. Optimal conditions
      for the purification of HbNFPLP either by ion-exchange chromatography or by heat
      treatment were established with recoveries of 70% and 85%, respectively. By
      extrapolation from the data in rats and rabbits a half life of about 8 hours can
      be expected in the circulation of humans. However, under some conditions a
      further prolongation is required. The aim of further modification of HbNFPLP was
      to achieve a retention time of about 24 hours. Polymerization with glutaraldehyde
      to polyHbNFPLP resulted in a mixture of polymers of different size. We determined
      the optimal degree of polymerization with respect to the effects on vascular
      retention time, oncotic activity, viscosity and oxygen affinity. Depending on the
      degree of polymerization we found in rats a 5- to 7- fold increase in vascular
      half-life compared to native Hb. The change in oxygen affinity was found to be
      independent of the polymer size (P50 = 18-22 mmHg). A limiting factor for
      polymerization is the increase in viscosity, which was dramatic when large
      polymers (greater than 300 kD) were present in the preparation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1391438
TI  - Hemoglobin tetramers stabilized with polyaspirins.
AB  - Organic acids activated by esterification with 3,5-dibromosalicylate react
      preferentially either with the beta 82 lysines or the alpha 99 lysines of
      hemoglobin. The versatility and site specificity of these polysapirins and the
      usage of both human and bovine hemoglobins allowed the construction of a family
      of oxygen carriers with various P50 ranging from 10 to 50 mmHg. These derivatives
      are obtained in pure homogeneous form by column chromatography. They are
      stabilized tetramers where the dissociation into dimers is inhibited. The latest
      addition is Tri-(3,5,dibromosalicyl)-benzenetricarboxylate, which crosslinks both
      human and bovine hemoglobin across the beta subunits, decreasing the oxygen
      affinity of both proteins. The crosslinked hemoglobins have a normal Bohr effect,
      more expanded in the alkaline region, and are sensitive to chlorides but not to
      polyphosphates. Solutions of stabilized tetramers, infused into rats or cats up
      to 25-50% blood replacement, do not produce altered renal and cardiac function.
      In the cat isovolemic hemodilution increases cerebral flow in controls treated
      with albumin solutions, when an oxygen carrier is used the cerebral flow remains
      normal.

PMID- 1391439
TI  - Synthesis and properties of polymerized, diaspirin cross-linked hemoglobins.
AB  - During the course of our studies it became clear that there were therapeutic
      applications for which a polymeric hemoglobin having an extended half-life in
      circulation would be appropriate. Therefore, a process for the glutaraldehyde
      polymerization of diaspirin cross-linked hemoglobin (DCLHb) was developed and
      used to prepare glutaraldehyde-polymerized DCLHb (GP-DCLHb) in lactated Ringer's
      solution in sufficient quantities for biological testing. Both isovolemic
      exchange-transfusion and "top-load" studies (rats; primates and swine,
      respectively) were completed in which a broad spectrum of physiologic,
      histopathologic and analytical parameters were monitored and assessed. In
      general, GP-DCLHb in lactated Ringer's solution was well-tolerated
      physiologically. When compared to DCLHb, GP-DCLHb offers the advantages of
      reduced renal clearance of hemoglobin and an extended half-life in circulation.
      GP-DCLHb has the disadvantages that (1) glutaraldehyde is an ineffective
      virucidal agent under the conditions of the polymerization reaction and a
      separate virus inactivation step is required; (2) low-endotoxin (LAL-negative) GP
      DCLHb solutions are pyrogenic (rabbits); and (3) unusual deposition of hemoglobin
      containing material in the small arterioles of the liver and kidney (rats) was
      sometimes seen even after a period of time (2 weeks) during which treatment
      related organ pathologies are usually resolved, a finding peculiar to GP-DCLHb
      among the various hemoglobin derivatives we have tested.

PMID- 1391440
TI  - Effects of hypothermic conditions on the oxygen carrying capacity of crosslinked
      hemoglobins.
AB  - In view of the potential application for hemoglobin-based oxygen carriers (HBOCs)
      in organ perfusion under hypothermic conditions, we examined the temperature
      dependence of oxygen equilibrium curves (OECs) at 15-37 degrees C of three HBOCs:
      HbA-FMDA and HbBv-FMDA, produced by the reaction of human or bovine oxyHb with
      fumaryl mono-dibromoaspirin, and HbA-DBBF, produced by the reaction of human
      deoxyHb with bis(3,5-dibromosalicyl) fumarate. OECs for HbA-DBBF, HbA-FMDA and
      HbBv-FMDA at 37 degrees C were right shifted (P50 = 24.5, 17 and 35 torr,
      respectively). van't Hoff's rule gave HbA-DBBF (-12.2 +/- 2.8), HbA-FMDA (-12.0
      +/- 2.0), HbBv-FMDA (-10.5 +/- 1.8); these values do not significantly differ
      from that for native HbAo (-11.5 +/- 2.4). Among the hemoglobins included in this
      study, HbBv-FMDA had the most favorable oxygenation characteristics at low
      temperatures (a P50 of 6.0 torr at 15 degrees C as compared to only 2-3 torr for
      the other hemoglobins in the study). Recently, however, a human hemoglobin
      crosslinked with bis-pyridoxyl tetraphosphate was reported to have a P50 of 15
      torr at 16 degrees C (Keipert et al, Transfusion 1989; 29: 768-773). Therefore,
      precise knowledge of the oxygen delivering capacity of any potential HBOC should
      be explored under hypothermic conditions as performance under these conditions
      may determine its usefulness as an organ perfusate.

PMID- 1391441
TI  - Bovine hemoglobin anaerobically reacted with divinyl sulfone: a potential source
      for hypothermic oxygen carriers.
AB  - The bifunctional reagent divinyl sulfone was anaerobically reacted with bovine
      hemoglobin to give a noncrosslinked intramolecularly-modified new derivative
      (HbBv-DVS). By employing a high molar ratio of divinyl sulfone to HbBv-DVS, it
      was possible to effect anaerobic intermolecular crosslinkage. The polymerized
      material (Poly HbBv-DVS) was shown to consist of a mixture of modified
      intermolecularly-crosslinked hemoglobins characterized by molecular masses
      ranging from 130 to -500 kDa. Some functional properties of HbBv-DVS and Poly
      HbBv-DVS have been evaluated in vitro and in vivo. Viscosities of HbBv-DVS
      solutions at temperatures as low as 15 degrees C and concentrations up to 14.0
      g/dl were proved to be much lower than that of normal human blood at 37 degrees C
      (-4 cp). Poly HbBv-DVS (14.0 g/dl) was iso-oncotic (COP = 23 mm Hg) with plasma,
      and had viscosities of 3.37 and 4.57 cp at 37 and 15 degrees C, respectively. The
      clearance of Poly HbBv-DVS from the circulation was significantly delayed (T1/2 =
      270 min), compared with those of HbBv and HbBv-DVS (T1/2 = 80 and 100 min,
      respectively. The P50 values were substantially increased (P50 = 52 and 61 mm Hg
      at 37 degrees C, 0.15 M Cl- and pH 7.4 for HbBv-DVS and Poly HbBv-DVS,
      respectively). Due to their right-shifted oxygen equilibrium curves, these
      derivatives still yielded P50 values of about 20 mm Hg at the low temperature of
      15 degrees C, as compared with only 7 mm Hg for native bovine hemoglobin. These
      properties make HbBv-DVS and Poly HbBv-DVS potential new candidates for low
      temperature organ perfusion.

PMID- 1391442
TI  - Hemoglobin-based oxygen carriers (HBOCs): structural alterations that affect free
      radical generation.
AB  - We examined how changes in oxygen affinity brought about by different chemical
      modifications of hemoglobins affect their oxidation-reduction reactions. The
      three modified hemoglobins studied were HbA-FMDA, HbBv-FMDA, produced by the
      reaction of human or bovine oxyHb with fumaryl mono-dibromoaspirin; and HbA-DBBF,
      produced by the reaction of human deoxyHb with bis(3,5-dibromosalicyl) fumarate.
      Exposure of oxyHb to H2O2 causes generation of free radicals capable of cleaving
      dimethylsulfoxide (Me2SO) to produce formaldehyde (HCHO). Relative to the
      reaction rate for HbAo (630 +/- 130 M/min) the rates of HCHO formation were
      roughly 70% for HbA-DBBF, 50% for HbA-FMDA and 16% for HbBv-FMDA. Exposure to
      H2O2 also caused spectral changes at varied rates for the HBOCs analyzed.
      Although these rates were not directly correlated with the rates of free radical
      formation, addition of mannitol or thiourea slowed both the rate of spectral
      changes and HCHO formation. The relative ability of the ferric derivatives of the
      HBOCs to participate in free radical reactions was monitored by assays of non
      enzymatic NADPH oxidation and aniline hydroxylation. HbBv-FMDA showed
      significantly slower rates than the other HBOCs in both assays. The observed
      differences between HBOCs in these assays indicate differences in their ability
      to generate or interact with free radicals.

PMID- 1391443
TI  - Stabilities and properties of multilinked hemoglobins.
AB  - Crosslinking of both human and dog hemoglobin has been done with a variety of
      reagents to produce singly, doubly and multiply crosslinked hemoglobins.
      Succinate and glutarate diaspirins did not crosslink deoxy human hemoglobin in
      good yield, in contrast to the fumarate analog (DBSF). Deoxy dog Hb did not react
      well with DBSF, but oxy dog Hb did react, giving crosslinked tetramers as well as
      dimers on SDS electrophoresis. Crosslinking with a short, rigid reagent
      (difluorodinitrobenzene) resulted in a similar product for both oxy and deoxy
      hemoglobin that had high stability and oxygen affinity. The trilinker, tris
      chloroethylamine, produced a more stable product than the corresponding
      crosslinker, bis-chloroethylamine. Double crosslinking oxy Hb with DBSF and
      dimethylpimelimidate or with DBSF followed by deoxygenation and recrosslinking
      with DBSF gave products with higher denaturation temperatures. The diaspirin
      double crosslinked product had high oxygen affinity.

PMID- 1391444
TI  - A new type of artificial oxygen carrier: soluble hyperpolymeric haemoglobin with
      negligible oncotic pressure--production of thermally stable hyperpolymers from
      human blood with glutaraldehyde as cross-linker.

PMID- 1391445
TI  - Molecular weight determinations of o-raffinose-polymerized human hemoglobin.

PMID- 1391446
TI  - Relationship between chemical properties and biological properties of
      pyridoxalated hemoglobin-polyoxyethylene.
AB  - Pyridoxalated hemoglobin-polyoxyethylene (PHP) is a conjugate of human hemoglobin
      with alpha-carboxymethyl, omega-carboxymethoxypolyoxyethylene(POE). This
      conjugate is selected as an oxygen carrier for blood substitute because it can
      survive for a long time in the circulation and also it can transport the same
      amount of oxygen as red cell. Optimization of PHP has been done by changing the
      degree of the modification and reaction procedures in order to adjust viscosity
      and colloid osmotic pressure to physiological values. The oxygen carrying
      capacity was physically evaluated by oxygen equilibrium curves and biologically
      by an ATP content in perfused isolated liver. Structural relationship of PHP to
      the binding properties to haptoglobin was studied and the effect of the POE
      modification on the binding properties was observed when the number of POE per
      one hemoglobin molecule is over six. Based on the comparative study of solubility
      of met-PHP and met-SFH, the POE modification was suggested to reduce the toxicity
      of hemoglobin against organs. Finally physical properties of PHP at low
      temperature was discussed in relation to organ preservation.

PMID- 1391447
TI  - Carbodiimide-mediated coupling of benzenepentacarboxylate to human hemoglobin:
      structural and functional consequences.
AB  - We have examined the covalent modification of HbA with BPC
      (benzenepentacarboxylate) whose carboxyl groups were activated with EDC [1-ethyl
      3-(3-dimethyl- aminopropyl)-carbodiimide]. Reaction of deoxy-HbA at pH 8 with a
      10-fold excess of BPC, preactivated with a 2-fold excess of EDC for 5 minutes,
      followed by anion-exchange chromatography, gives three components with p50 values
      of 1.15 (unreacted HbA), 11.7 and 7.6 mm of Hg at 20 degrees C (50 mM Bis-Tris pH
      7.0). Component III does not dissociate into dimers upon dilution, but components
      I and II do. When deoxy-HbA is reacted at pH 6 with 10-fold BPC, preactivated
      with two-fold EDC for 5 minutes, the resultant HbA derivatives can be separated
      into three components, with p50 values at pH 7 of 14.2, 10.2 and 5.2 mm of Hg,
      respectively. All three components are stable tetramers. Oxygen binding by all of
      the covalent HbA-(BPC)x complexes is cooperative, pH sensitive, but IHP
      insensitive. The latter observation suggest that BPC is covalently bound to HbA's
      DPG/IHP binding site. This conclusion is corroborated by reversed phase HPLC
      analysis which shows that all five modified HbAs contain at least one modified
      beta chain. In addition, 4 of the 5 derivatives also contain modified alpha
      chains. No inter or intratetramer crosslinks are observed.

PMID- 1391448
TI  - Stabilized hemoglobins as acellular resuscitative fluids.
AB  - This study reports some recent work dealing with the stabilization of the
      tetramers of hemoglobin. It is shown that by using a variety of diacids, it is
      possible to increase the P50 above that of stroma free hemoglobin. In order to
      lengthen the retention times in the circulatory system, the stabilized
      hemoglobins were complexed with both hydroxyethyl starch polymers and polyol
      tetronic polymers. The resulting hemoglobin-polymer compounds were then freeze
      dried. It was possible to reconstitute the powder by the addition of
      physiological saline when needed. The methods presented here appear to be appear
      to be as effective as using pyridoxal phosphate but at a fraction of the cost.

PMID- 1391449
TI  - Synthesis and characterization of artificial red cell (ARC).
AB  - An unsaturated lipid made from 2,4-octadecadienoic acid was used as a component
      of phospholipid vesicles. The vesicles (0.2 micron phi) was prepared by an
      extrusion method, and the unsaturated lipid was polymerized with gamma-ray.
      Vesicles constructed from the polylipid show enormous stability during long term
      storage in frozen state and can be handled easily. Negative effect could not be
      confirmed in vitro tests. This system satisfies all the physiological conditions,
      such as oxygen transport ability and solution properties as a blood substitute.

PMID- 1391450
TI  - Preparation, properties and biological function of liposome encapsulated
      hemoglobin.

PMID- 1391451
TI  - Liposome-encapsulated hemoglobin processing methods.
AB  - An effective and safe red blood cell substitute is being developed based on
      double emulsion/evaporation techniques followed by high pressure homogenization
      to form liposome-encapsulated hemoglobin (LEH). Formulations are made up of
      hydrogenated phosphatidylcholine (PC, soy or egg), cholesterol,
      phosphatidylinositol (PI), and alpha-tocopherol in a molar ratio of 1:1:0.2:0.02,
      respectively. Resulting LEH-encapsulated hemoglobin (Hb) concentrations are
      greater than 80% of precursor Hb solutions. Met-Hb generation accompanying LEH
      processing appears to be small with only a 3% increase for encapsulated over
      precursor. These results correspond to an oxygen content for an LEH suspension
      sample (50% by volume LEH) of 15 volume% oxygen. Oxygen affinity and
      cooperativity values for LEH suspensions appear to be near the normal values
      expected for whole blood. The viscosity of LEH suspension samples (50% by volume
      LEH in phosphate-buffered saline containing 7.5 wt% albumin) were slightly higher
      than that of whole blood. The effect of shear rate on leakage of encapsulated Hb
      from LEH was small, i.e. 0.5% or less. Nearly total isovolemic exchange
      transfusion using a cannulated rat model demonstrates efficacy of LEH suspension
      samples. There appears to be no difference in rat internal organ weights between
      rats exchanged with control compared to rats exchanged with LEH. Circulation half
      life following 50% isovolemic exchange-transfusion is about 15 to 18 hours.

PMID- 1391452
TI  - Preparation of carboxymethylchitin-incorporated submicron bilayer-lipid membrane
      artificial cells (liposomes) encapsulating hemoglobin.

PMID- 1391453
TI  - Purification and quantitative determination of carboxymethylchitin incorporation
      into submicron bilayer-lipid membrane artificial cells (liposomes) encapsulating
      hemoglobin.
AB  - The separation of carboxymethylchitin-coated hemoglobin-loaded liposomes (CMC
      LEHb)s from the non-adsorbed CMC has been achieved by gel chromatography. This
      purification takes place at the physiological pH of 7.4 favoring HbO2
      preservation. A comparative study between experimental techniques for the
      quantitative determination of the absorption of carboxymethylchitin (CMC) onto
      liposomes encapsulating hemoglobin (LEHb)s has been conducted. Results suggest
      that FT-IR spectroscopy gives a more accurate quantitative absorption index while
      the chitinase-based enzymatic assay should be used as a qualitative detection
      tool. Quantitative bilayer and surface characterization show that the RBC
      membrane composition has been closely simulated by that of CMC-LEHbs in terms of
      total lipids and carbohydrates at 87.8% (phospholipids and cholesterol) and 12.2%
      CMC respectively.

PMID- 1391455
TI  - Oxygen-transport and solution properties of polylipid/Hb vesicles (ARC).
AB  - Polymerized phospholipid vesicle encapsulating Hb (polylipid/Hb vesicle) was
      prepared from a mixture of unsaturated phospholipid, cholesterol and unsaturated
      fatty acid and polymerization by gamma-ray irradiation. The average radius of
      resulting vesicles was 203 +/- 39 nm and concentrated Hb (30 wt%) was efficiently
      encapsulated. gamma-Ray polymerization proceeds theoretically at low temperature
      (4 degrees C). P50 and oxygen transporting efficiency were adjusted to 40 mmHg
      and 40%, respectively. Oncotic pressure and solution viscosity can be controlled
      to the same values as blood.

PMID- 1391454
TI  - Large-scale blood substitute production using a microfluidizer.
AB  - Microfluidization has been tested as a way to disperse phospholipids in aqueous
      hemoglobin solutions. Spherical and stable liposomes of 2 to 3 microns were
      obtained. Lipid incorporation (up to 85%) and hemoglobin encapsulation (up to
      15%) in liposomes have been improved with respect to previous investigations.
      However, results show that a more efficient dispersion system using lower
      concentrations of lipid is required to obtain a high liposome hemoglobin
      concentration (limited actually to 150 g/l) and an economically and biologically
      suitable process for artificial blood production at large scale.

PMID- 1391456
TI  - Studies on the quality control of stroma-free hemoglobin.
AB  - Analytical methods for phospholipids and blood group antigen were developed using
      HPLC-UV and EIA, respectively, for the quality control of SFH. These methods had
      sensitivities superior to those of conventional assays. In addition, the HPLC
      method could isolate PS, which might play an essential role in blood coagulation.
      The above analytical methods were applied to evaluate three representatives SFH
      preparation methods, 36,000xg centrifugation followed by the filtration with a
      0.22 um filter, ultrafiltration with a 100 kd membrane, and filtration with the
      BMM-40 nm membrane. Both the BMM method and the ultrafiltration method were shown
      to remove more than 99.7% of phospholipids, and more than 99.99% of blood group
      antigen. On the other hand, the centrifugation preparation still contained much
      of both components. The BMM filter was originally developed as a virus removal
      filter. The virus removal efficiency of the BMM-40 nm was examined with a genetic
      technique, the PCR method. The BMM-40 nm was demonstrated to remove HB viruses
      with an efficiency of eight log or more. These results indicate that the BMM is a
      useful filter to prepare a stroma-free, virus-reduced hemoglobin solution.

PMID- 1391457
TI  - Pilot scale production of pyrogen-free human hemoglobin for research.
AB  - A pilot scale production facility for the preparation of 20 to 30 liters of
      stroma-free hemoglobin is described. The system is capable of producing pyrogen
      free solutions for research purposes. It is not certified for production of
      parenteral solutions for human use, but the plan could be implemented to meet
      standards for such materials. Products of the facility should be of adequate
      quality to address most of the toxicity and efficacy issues facing further
      development of hemoglobin-based red cell substitutes.

PMID- 1391458
TI  - Preparation and characterization of diaspirin cross-linked hemoglobin solutions
      for preclinical studies.
AB  - During 1990 and 1991 the capability for repetitive, consecutive production of
      DCLHb solution to meet a rigorous and complete set of product criteria was
      demonstrated. In addition, through periodic monitoring of product stored under
      controlled conditions, the stability of all lots of DCLHb solution during frozen
      storage was demonstrated for more than a year. In this way, assurance was
      provided that the DCLHb solution used in preclinical testing met all product
      criteria throughout the biological testing period.

PMID- 1391460
TI  - Detection of membrane fragments in hemoglobin solutions.
AB  - Two methods for the detection of membrane components in human stroma-free
      hemoglobin (SFHb) solutions are described. The first method is a phospholipid
      assay with a detection limit of 0.5-1 nmol phospholipid/ml SFHb. For the
      detection of membrane proteins an immunoassay with a monoclonal antibody against
      glycophorin alpha was developed (detection limit 0.01% of the original amount).
      The determination of both glycophorin alpha and phospholipid yields useful
      information on the purity of SFHb solutions, as was shown by determination of the
      purity of two SFHb solutions prepared in different ways.

PMID- 1391459
TI  - Large scale production and characterization of lyophilized pyridoxalated
      hemoglobin-polyoxyethylene (PHP).
AB  - Lyophilized PHP as an oxygen carrier is prepared from outdated red cell and
      dicarboxymethylated polyoxyethylene. In order to apply PHP for a clinical use, a
      large scale production of high quality PHP has been studied. We have set up a 20
      L scale production flow of PHP88. The product was tested to confirm the quality
      and lot-to-lot consistency. The blood group specific materials were weakly
      positive in stroma-free hemoglobin (SFH), however, were found negative in the PHP
      of this scale. The amount of phosphatidylethanolamine (PE) in purified SFH and
      PHP88 reconstituted solution was 0.19 +/- 0.04 and 0.03 +/- 0.01 ppm,
      respectively. Contamination of viruses such as HBV and Non A non B hepatitis
      virus could not be observed in the final product. Elimination and inactivation of
      HIV was validated through a spike test. The characterizations of the final
      products in 20 L scale were done through MW, P50, Hill coefficient, viscosity,
      and molecular weight distribution by SDS-PAGE and batch to batch consistency was
      also confirmed. The results show that production process is appropriate to
      eliminate the blood group materials, PE and virus, and produce PHP of high
      quality. Lyophilized PHP88 can be produced by addition of maltose and can be
      stored over 1 year.

PMID- 1391461
TI  - Possible importance of chromatographic purification position in a blood
      substitute elaboration process.
AB  - Purification of hemoglobin (Hb) solutions suggested as oxygen carriers is an
      imperative necessity. All processes currently used clear out the solutions of
      almost the totality of impurities that are able to negatively influence the
      transfusional efficiency of Hb. We have studied the stability (metHb measurement)
      of Hb purified by DEAE dextran chromatography (Spherodex, 10 mM phosphate buffer,
      pH 7.20) which eliminates lipopolysaccharides, enzymes and non heminic-proteins
      ... without denaturing Hb. In spite of the improvements due to this purification
      method on the transfusional efficiency of non modified Hb solutions, the lack of
      enzymes involved in the protection of Hb against autooxidation (superoxide
      dismutase, peroxidase, catalase ...) makes it much more vulnerable to the
      reagents used during the following chemical processes: pyridoxylation,
      polymerization or macromolecule binding, thereby leading to an important
      oxidation to metHb. These observations led us to question the optimal position of
      purification in a process of modified Hb preparation. We have shown the
      importance of this chromatographic position in working on pyridoxylated Hb bound
      to monomethoxypolyoxyethylene. Spherodex chromatography appears to be a very
      satisfactory purification method, provided it occurs only at the last step of the
      process. Many authors have not been attentive to this phenomenon which could be
      found with other Hb modifications. This therefore imposes to study the best place
      to incorporate a particular purification step into a hemoglobin preparatory
      procedure.

PMID- 1391462
TI  - Development of analytical methods to evaluate SFH.
AB  - For the determination of stroma content in SFH, two analytical methods were
      developed, the HPLC-UV for phospholipids and the enzyme immunoassay for blood
      group antigen. These analytical methods were applied to evaluate three
      representative SFH preparations. The 36,000 x g centrifugation method was shown
      to contain higher amount of stroma components. On the other hand, the BMM-40 nm
      and the ultrafiltration method with a 100 kd membrane was shown to remove more
      than 99.7% of phospholipids and almost all of blood group antigen from hemoglobin
      solutions. These results demonstrated that these analytical methods were very
      useful in evaluating any highly purified hemoglobin solutions.

PMID- 1391464
TI  - Endotoxin removed from hemoglobin solution using polymyxin-B immobilized fibre
      (PMX-F) followed by a new turbidometric endotoxin assay.
AB  - Endotoxin contamination in modified hemoglobin can result in side effects.
      Accurate measurement and effective elimination of endotoxin are important in
      producing safe hemoglobin preparation. A new turbidometric endotoxin assay
      (Toxinometer) was studied, in which absorbance of wavelength was applied at 660
      nm. This method is not affected by the presence of hemoglobin in solution. This
      way, toxinometer can accurately measure endotoxin concentration in hemoglobin
      solution. For the elimination of endotoxin, polymyxin-B immobilized fiber (PMX-F)
      was studied in-vitro and compared with commercial materials. The PMX-F was found
      to be a convenient and less expensive approach.

PMID- 1391463
TI  - Trace element analyses of diaspirin cross-linked hemoglobin solutions.
AB  - A sensitive assay using inductively coupled plasma atomic emission spectroscopy
      (ICP-AES) has been applied to the measurement of trace elements in diaspirin
      cross-linked hemoglobin (DCLHb) solutions. Calcium, magnesium, zinc and iron were
      the only elements detected at greater than background levels. Ag, Al, As, B, Ba,
      Bi, Cd, Co, Cr, Cu, Mn, Mo, Pb, Sb, Se, Si, Sr, Ti, and V were present at
      concentrations either equal to the acid blanks or were not detected. Detection of
      non-heme iron (not incorporated into the hemoglobin porphyrin ring) in a 10 g/dL
      hemoglobin solution required the development of a special protocol. In this
      protocol a chelator, DTPA, was added to hemoglobin solutions to complex with both
      free and non-specifically bound non-heme iron. The resulting iron:DTPA complexes
      were separated from the hemoglobin molecules by ultrafiltration and the ultra
      filtrate analyzed by ICP-AES. A modification of this assay in which the DTPA was
      omitted was used to measure the free non-heme iron in solution. Typical
      concentrations of chelatable (free and non-specifically bound) and solution
      (free) non-heme iron in DCLHb production lots at the completion of manufacture
      were 0.5-1.0 ppm and 0.1-0.3 ppm, respectively.

PMID- 1391465
TI  - Conceptual design and cost estimate for a modified hemoglobin production plant.
AB  - Polymerized, pyridoxalated stroma-free hemoglobin (Poly PSFH), made from outdated
      human blood, has excellent attributes for use as a blood substitute. A
      hypothetical larger scale process for the production of Poly PSFH is detailed,
      and facility design and cost estimates are presented. This paper gives the
      opportunity to discuss the engineering activities of process scope definition,
      utilities selection, and aseptic processing techniques, etc. Compliance with cGMP
      and other FDA regulation will also be discussed.

PMID- 1391466
TI  - Expression and assembly of functional human hemoglobin in S. cerevisiae.

PMID- 1391467
TI  - The purification and comparative analysis of hemoglobin from animal bloods.
AB  - Various methods for the separation and purification of Hb from animal blood have
      been investigated to establish the optimal and highly reliable purification
      process. The Hb obtained from various sources, i.e., bovine, pig and human bloods
      were analyzed and compared using simple and fast analytical methods, including,
      electrophoresis, isoelectric focusing, and spectroscopy to study the
      characterization of protein structure. Further investigation along this line will
      enable us to realize the ultimate objectives of development for artificial RBC
      substitutes.

PMID- 1391468
TI  - Large scale preparation of functional human placental hemoglobin for use in blood
      substitutes.

PMID- 1391469
TI  - Diaspirin cross-linked hemoglobin solution as a resuscitative fluid following
      severe hemorrhage in the rat.
AB  - The effect of diaspirin cross-linked hemoglobin (DCLHb) on mean arterial pressure
      (MAP) and heart rate (HR) was compared to Ringer's lactate (RL) and shed blood in
      a 70% lethal model of hemorrhage (35 cc/kg blood loss) in conscious rats. All
      animals resuscitated with DCLHb regardless of dose (17.5 and 35 cc/kg) and
      concentration (7% and 10% solution) exhibited complete restoration of MAP and HR
      which was maintained for at least 5 hrs. Hemodynamic responses in DCLHb-treated
      animals were not significantly different from 35 cc/kg blood-treated animals. In
      RL (105 cc/kg) treated animals the MAP was restored to 60-70% of baseline. 24 hr
      survival in animals resuscitated with fluids ranged between 88-100% and was not
      significantly different between treatment groups.

PMID- 1391470
TI  - Dehydration and shock: an animal model of hemorrhage and resuscitation of
      battlefield injury.
AB  - We have developed a porcine model of the anticipated military use of oxygen
      carrying resuscitation solutions. The objective is to determine whether toxicity
      under adverse conditions will limit further development of hemoglobin-based
      products. Splenectomized immature female swine are used because of their
      extensive use in the evaluation of other resuscitation solutions. Five days prior
      to each experiment, central vascular catheters and a renal arterial flow probe
      are surgically placed in the animals. After recovery and weight gain has resumed,
      animals are placed in metabolic cages and deprived of water for 48 hours to
      produce hyperosmolar dehydration resulting in loss of approximately 7% of body
      weight. We remove 38% of estimated blood volume, 25 ml/kg, over one hour by a
      controlled logarithmic hemorrhage. Resuscitation is by administration of a fixed
      volume of test solution. Hemodynamic function is observed but not further therapy
      is given for three hours, a period corresponding to evacuation in the field.
      After this period, corresponding to arrival at a field hospital, the animals'
      blood is returned. Swine are then observed in metabolic cages for an additional 7
      days while blood and urine are sampled daily. At the end of this period, animals
      are anesthetized, urinary catheters are implanted, and creatinine clearances are
      measured. Swine are than euthanized, and their tissues are examined. In a pilot
      study, resuscitation was performed with either Ringer's lactate, albumin, stroma
      free hemoglobin, or cross-linked (alpha alpha Hb) hemoglobin. All animals
      survived.

PMID- 1391471
TI  - Effect of a single replacement of one of Ringer lactate, hypertonic
      saline/dextran, 7g% albumin, stroma-free hemoglobin, o-raffinose polyhemoglobin
      or whole blood on the long term survival of unanesthetized rats with lethal
      hemorrhagic shock after 67% acute blood loss.
AB  - This study is based on an unanesthetized lethal hemorrhagic shock rat model (67%
      blood volume bled in 2 stages). The 8 groups studied were as follows. 1. Control-
      no resuscitation fluid. 2. Reinfusion of rat's own shed whole blood. 3. Ringer
      lactate solution--3 times shed blood volume. The following 4 fluids were each
      given as equal to the shed blood volume. 4. 7.5g% NaCl hypertonic saline/6%
      Dextran 70, followed by 3 volumes Ringer lactate dextran. 5. Ringer lactate
      solution. 6. Human albumin 7g% in Ringer lactate. 7. Stroma-free hemoglobin in
      Ringer lactate 8. o-raffinose polyhemoglobin in Ringer Lactate. Blood pressure
      and other vital signs were recorded continuously during the control period,
      bleeding periods, infusion period and 60 minutes after infusion. After this all
      surviving animals were followed for 14 days with no other special treatments.
      Group 4 had transient (10 minutes) returned of blood pressure to control levels.
      The 3 groups with sustained blood pressure at control level when followed for 1
      hour were groups 2, 6 and 7. The 2 groups with 100% survival on days 14 were
      group 2 and group 7.

PMID- 1391472
TI  - PEG-bovine hemoglobin: safety in a canine dehydrated hypovolemic-hemorrhagic
      shock model.
AB  - An initial evaluation of PEG-bHb was performed using a modified hypovolemic shock
      model. PEG-bHb had a substantially longer intravascular half-life than native Hb
      and no measurable hemoglobinuria was observed in the canine. PEG-bHb allowed
      successful resuscitation with an oxygen carrying capacity of 14-22% over that of
      lactated Ringer's solution.

PMID- 1391473
TI  - Resuscitation of bled dogs with pyridoxalated-polymerized hemoglobin solution.
AB  - We bled 25% of estimated total blood volume, then infused pyridoxalated
      polymerized human stroma-free hemoglobin solution (PP-SFH) (10 g/dl) to dogs
      under anesthesia in a volume equal to the blood removed. Central hemodynamics,
      blood flow distribution to organs, and renal function were studied up to 2-3
      hours following the infusion. Mean arterial pressure was reduced from 120 +/- 3
      to 86 +/- 7 mmHg at the end of the 30-minute hypovolumic period and the cardiac
      output was reduced by 27%. Immediately following the PP-SFH infusion we observed
      a further fall in blood pressure (43%) caused by a fall in cardiac output which
      lasted for 10 minutes. Blood pressure was restored gradually with the
      continuation of the infusion and the cardiac output was restored and maintained
      well. During the hypovolumic period, blood flow to the heart, renal cortex, and
      liver were reduced, whereas normal flow to the renal medulla and brain were
      maintained. After the resuscitation, blood flow to the heart, brain, liver, and
      renal medulla significantly exceeded the normal range, but remained subnormal in
      the renal cortex. Glomerular filtration rate (GFR), urine flow, and electrolyte
      excretion were all reduced during the hypovolumic period and were not restored to
      the pre-bleed levels after the infusion.

PMID- 1391474
TI  - Study of effect of the newly developed artificial blood "Neo Red Cells (NRC)" on
      hemodynamics and blood gas transport in canine hemorrhagic shock.
AB  - The purpose of this study is to evaluate the newly developed liposome
      encapsulated hemoglobin, named Neo Red Cells (NRC), in the treatment of
      hemorrhagic shock. The particle size of NRC is 180 +/- 88 nm, the hemoglobin
      concentration is 5.6 g/dl, the viscosity is 2 cp and P50 is 49.5 mmHg. The
      experiment was carried out on six mongrel dogs suffering hemorrhagic shock. Blood
      was extracted from the femoral artery and blood pressure became lower than 60
      mmHg. NRC in amount equal to the amount of blood extracted was transfused
      immediately. Inhalating normal room air, the above manipulation was repeated 3-5
      times. After 59% to 88% blood exchange using NRC, the total peripheral vascular
      resistance index (TPRI) was reduced and the cardiac index (CI) was increased,
      thereby alleviating the burden on the heart. The reduction of TPRI in the
      presence of hemorrhagic shock is presumed to be due to the small size of the NRC
      granules and their low viscosity. As the exchange rate increased, the oxygen
      consumption (VO2) increased remarkably, presumably due to the increase of CI and
      A-V difference of oxygen content. The conclusion of the study is that NRC is more
      suitable than natural blood for the treatment of hemorrhagic shock.

PMID- 1391475
TI  - Modified hemoglobin solution as possible perfusate relevant to organ
      transplantation.
AB  - A modified hemoglobin solution (<pyridoxylated hemoglobin>-<polyoxyethylene>
      conjugate solution, PHP solution) has very interesting characteristics such as
      oxygen-carrying property without corpuscular components. Experimental use of the
      PHP solution has shown promising possibilities as a perfusate relevant to organ
      transplantations. 1) Elongation of warm ischemic time in canine kidneys: Dogs
      survived even with the unilateral kidneys which had been exposed up to 4.5 hour
      warm ischemia and, thereafter, perfused with the PHP solution. 2) Elongation of
      perfusion preservation period of canine livers: Dogs survived with the
      transplanted livers which had been perfused for 48 hours with the PHP solution.
      3) Successful perfusion of rat small intestine: Lewis rat intestines perfused and
      preserved for 12 hours with the PHP solution showed a higher survival rate
      compared with those with Collins or UW solution. 4) Removal of antibodies: By
      exchange transfusion with a total of 30-60 ml of the PHP solution, a Lewis rat
      hematocrit lowered to 5% while IgG went down to nil from 8970 mg/dl, IgA to 28
      mg/dl from 118 mg/dl and IgM to 190 mg/dl from 897 mg/dl. This technique is
      expected to be applicable for removal of the naturally existing antibodies in
      xenotransplantation.

PMID- 1391476
TI  - Does oxygen supply improve graft viability in liver preservation?
AB  - While the clinical results of orthotopic liver transplantation have greatly
      improved, the viability of liver grafts and extension of the safe time for
      preservation are necessary factors in need of improvement. The liver is one of
      the organs most sensitive to anoxia. The addition of an oxygen carrying agent to
      the preservation solution was evaluated. Pyridoxalated hemoglobin-polyoxyethylene
      conjugate (PHP) is used as an oxygen carrier. Viaspan (UW) served as a control
      solution. Test solution (PHP+UW) composition was composed of a 1:1 mixture of PHP
      and UW solutions with hemoglobin 4.0g%, hydroxyethyl starch 2.5g%, osmolality 320
      mOsm/kg H2O, and colloidal osmotic pressure 33 mmHg. The oxygen carrying capacity
      of PHP+UW solution is about 10 times higher than UW solution at 4 degrees C. Male
      Lewis rats (BW: 250-300 g) were divided into five groups. After flushing the
      solution via the portal vein, rat livers were harvested. Two preservation
      methods, simple storage and perfusion (0.1 ml/min/g liver), were studied at 4
      degrees C for 24 or 48 hours. OxyHb, MetHb, pO2, pH, Na, K, GOT, and GPT of
      perfusate, hepatic mitochondrial functions after preservation, and tissue adenine
      nucleotides by HPLC were measured. Light microscopy on the tissue was also
      performed. No significant differences were noted in perfusate biochemical
      parameters. Oxygen consumption during the perfusion was significantly higher in
      the PHP+UW than in the UW group. Hepatic mitochondrial functions and tissue ATP
      levels were better preserved in perfusion than in simple storage, and in PHP+UW
      than in UW at 48 hours. The oxygen carrying agent, PHP, can provide significantly
      higher levels of oxygen to liver grafts and improve graft viability.

PMID- 1391477
TI  - Machine perfusion of isolated kidney at 37 degrees C using pyridoxalated
      hemoglobin-polyoxyethylene (PHP) solution, UW solution and its combination.
AB  - To preserve isolated kidney normothermically, PHP containing UW components were
      evaluated as perfusates. Kidneys were flushed out by Lactate Ringer solution
      immediately after isolation from mongrel dogs, and then connected to the
      perfusion circuit which consists of a preservation box, a reservoir of perfusate,
      a membrane oxygenator and a drive unit. PHP containing 140 mEq/l of Na+ and 4
      mEq/l of K+ (PHP(E)), UW solution (UW) and UW components added PHP(E) were
      prepared and adjusted at pH 7.4 prior to use. Temperature and perfusion pressure
      were controlled at 37 degrees C and 100 mmHg, respectively. During 12 hour
      perfusion, remarkable changes in pH were seen in UW group and PHP group while
      higher oxygen consumption was noted in PHP(E)+UW group than that in PHP(E) group.
      The histological findings showed moderate damages of tubular epithelial cells and
      maintaining normal glomerular structure in PHP(E)+UW while severe damage of both
      tubulus in UW group were seen. There was no edematous degeneration in both UW and
      PHP(E)+UW groups, however, it was seen in PHP(E) alone. It was suggested that
      components of UW solution have positive effect on normothermic machine perfusion
      with PHP(E) solution.

PMID- 1391479
TI  - A preclinical screening test for modified hemoglobin to bridge the gap between
      animal safety studies and use in human.
AB  - The infusion of large amount of modified hemoglobin as blood substitute can
      potentially result in hypersensitivity and anaphylactic reactions, antibody
      antigen reactions and others. Animal safety studies are important. However,
      response in animals may not be the same as in human. Before injecting into human,
      we may need to use an in-vitro screening procedure. One approach is based on
      testing the effects of modified Hb on complement activation (C3a) of human
      plasma. This paper describes this screening test. It also discusses how this may
      potentially be used. For instance using this to test for contamination from trace
      membrane fragments with blood group antigen or lipids, antibody-antigen
      complexes, endotoxin, trace fragments of microorganisms, residual amounts of some
      polymers, emulsifying agents, and organic solvents. There is also the possibility
      of obtaining plasma from a very large human population and analyse each of these
      to study the epidemiology of adverse reactions in different groups and types of
      patients.

PMID- 1391478
TI  - Evaluation of a pyridoxylated hemoglobin polyoxyethylene conjugate solution as a
      perfusate for small intestine preservation.
AB  - A new type of artificial blood, pyridoxylated hemoglobin-polyoxyethylene
      conjugate (PHP) solution, (developed by PHP research group of the department of
      health and welfare of Japan, and produced by Ajinomoto Co., Inc. Tokyo) as an
      oxygen-carrying component, has been recently devised using hemoglobin obtained
      from hemolyzed human erythrocytes. Recently, the studies using this solution as a
      preservation solution were performed in some instances. To examine the mechanism
      of improved viability using this solution as a preservation solution, we
      developed a model of orthotopic small intestine transplantation (OIT) in the rat.
      As a baseline study, we compared parameters of viability of the grafts preserved
      in Collins and UW solution to those preserved in PHP solution including a
      survival rate, a serum level total protein and albumin, and a change in body
      weight after transplantation. In our study, the simple hypothermia storage
      together with intestinal perfusion preservation with PHP solution was performed.
      Animals were divided into 6, 12, and 24 hr preservation groups. All of the rats
      survived after 6 hr preservation following transplantation. However, in 12 hr
      storage, five of six rats in PHP solution preservation survived and recovery in
      body weight after grafting was better than those with Collins and UW solution. We
      conclude that the PHP solution is, therefore, considered to possibly be a more
      suitable perfusate for small intestine preservation than Collins and UW solution.

PMID- 1391480
TI  - Evaluating new red cell substitutes: a critical analysis of toxicity models.
AB  - Because red cell substitutes (RCS) will improve oxygen delivery to tissues
      rendered hypoxic or anoxic they are presumed to be effective. Prior to clinical
      application the safety--toxicity of any proposed solution must be established.
      Models used to demonstrate efficacy do not necessarily evaluate toxicity.
      Infusion of human hemoglobin (Hb) solutions into animals raises one issue of
      immune response but obviates looking at the human response to similar materials.
      Differentiating the cause of an immunologic effect may be difficult. Effects seen
      in acute models may not have chronic implications; they may be transients of no
      consequence. Differentiating the effects of volume load intravascularly from the
      effects of the solution is also a problem. Identification of proper controls is
      essential for evaluation. However, the control solution may have problems of its
      own that must be defined. For any proposed RBS a menu of models exploring
      cellular, tissue, organ and organism responses to the solution, its residual
      modifiers and the products of metabolism are needed to define primary and
      secondary effects.

PMID- 1391481
TI  - Effects of intravenous infusions of diaspirin cross-linked hemoglobin (DCLHb) on
      sheep.
AB  - The purpose of this study was to compare the cardiopulmonary, hematologic, and
      immunologic responses of unanesthetized sheep to single, "topload", intravenous
      infusions of either 10 mL/Kg or 40 mL/Kg of Diaspirin Cross-Linked Hemoglobin, 10
      mL/Kg or 40 mL/Kg of a Human Serum Albumin (HSA) solution oncotically adjusted
      with human serum albumin to approximately match the oncotic pressure of the
      DCLHb, or 10 mL/Kg of Erythrocyte Hemolysate solution prepared in a manner
      similar to that commonly described in the literature and referred to as "stroma
      free hemoglobin". Solutions were infused at a rate of 1 mL/Kg/minute and animals
      were monitored for 72 hours after infusion. These studies demonstrated that in
      sheep infusion of either DCLHb or HSA solutions was well tolerated and did not
      produce a significant increase in plasma C3a levels, an increase in the plasma
      concentration of thromboxane B2, or unexpected fluid shifts. In contrast,
      infusion of the Erythrocyte Hemolysate produced a greater than 10-fold increase
      in plasma C3a concentrations, a greater than 6000-fold increase in plasma TxB2
      concentration, significant fluid shifts, and changes in a variety of other
      parameters consistent with induction of a dramatic inflammatory response. These
      results indicate that appropriately prepared and purified DCLHb solutions do not
      elicit an inflammatory reaction in sheep.

PMID- 1391482
TI  - Pharmacokinetic studies in the rat on a o-raffinose polymerized human hemoglobin.
AB  - We have studied the plasma half-life (T 1/2), oxygen-binding affinity (P50),
      organ distribution, and excretion of the individual molecular weight (MW)
      components of human hemoglobin polymerized with periodate-oxidized, ring-opened
      raffinose (oR poly-Hb), following transfusion in the rat. The model was an
      isovolemic 50% exchange transfusion in the conscious, chronically catheterized
      rat. Total plasma Hb levels yielded a (T 1/2) of 10 to 11 hr for oR poly-Hb. The
      T 1/2 values of individual MW components of the poly-Hb as determined by size
      exclusion HPLC were approximately: 4 hr for the monomeric fraction (Hb)1, 9 hr
      for the dimer (Hb)2, and 15 hr for the fraction representing trimers to nanomers
      (Hb)3-9. The P50 values of plasma samples containing oR poly-Hb (collected from 0
      24 hr after exchange) remained unchanged at 28 +/- 3 mmHg. oR stabilized and
      polymerized Hb were not excreted via the kidneys. Hepatic and renal distribution
      as well as plasma and renal clearance were determined by liquid scintillation
      counting using individual tritium [3H] labelled MW components purified from [3H]
      oR poly-Hb: (Hb)1/2, (Hb)1, (Hb)2, (Hb)3&4, and (Hb) greater than 9. In kidney,
      uptake (determined by the relative concentration of radioactivity) decreased with
      increasing MW of the labelled component. Conversely, in liver, uptake increased
      with increasing MW. Plasma and renal clearance results were consistent with those
      obtained by HPLC analysis. Hematocrit levels returned from a 20% post-transfusion
      level to normal pre-transfusion levels (44%) within 10 days after the exchange.

PMID- 1391483
TI  - Immunogenicity of diaspirin cross-linked human hemoglobin solutions.
AB  - To assess the potential immunogenicity of human diaspirin cross-linked hemoglobin
      (DCLHb) solution, repetitive doses of this material were given intravenously to
      rhesus monkeys at monthly intervals and the immune response to this challenge was
      assessed. Serum samples collected at multiple intervals throughout the study
      showed no evidence of DCLHb specific IgG or IgM production. Intradermal skin
      tests performed one month after the final DCLHb infusion were also negative.
      These data demonstrate that DCLHb is not antigenic when administered
      intravenously to rhesus monkeys. In addition, screening of a panel of normal
      human sera for pre-existing anti-DCLHb IgG antibodies was negative, suggesting
      that this modified hemoglobin is unlikely to be antigenic in humans.

PMID- 1391484
TI  - Immunological effects of hemoglobin, encapsulated hemoglobin, polyhemoglobin and
      conjugated hemoglobin using different immunization schedules.
AB  - Repeated subcutaneous immunizing injections into rats of Freund's adjuvant
      containing rat hemoglobin or o-raffinose rat polyhemoglobin did not result in
      increase in IgG antibody titers. However, heterologous hemoglobin injected as
      above is antigenic (49.50 + 6.70 % CPM). Crosslinking heterologous hemoglobin
      into o-raffinose polyhemoglobin further increased its antigenicity (75.60 +
      4.08). Thus, unlike homologous hemoglobin, cross-linking of heterologous
      hemoglobin increased its antigenicity. Liposome encapsulated homologous
      hemoglobin injected subcutaneously with or without Freund's adjuvant did not show
      antigenicity. Encapsulated heterologous hemoglobin resulted in a minimal increase
      in antibody titers (10.73 + 4.64) only with Freund's adjuvant, but no increase
      when injected without Freund's adjuvant. Conjugated heterologous hemoglobin (PEG
      Hb) injected intravenously by itself at weekly intervals did not result in
      significant increase in antibody titers on the 5th week.

PMID- 1391485
TI  - Liposome encapsulated hemoglobin: long-term storage stability and in vivo
      characterization.
AB  - Liposome Encapsulated Hemoglobin (LEH) has been the focus of research and
      development at the Naval Research Laboratory in an effort to find a viable oxygen
      carrying resuscitative fluid. Previous reports from our laboratory have shown
      that LEH binds and releases oxygen in a manner similar to red blood cells, and
      that it can sustain life when red cell hematocrits are decreased to critical
      levels. We have also reported on LEH with regards to preparative methods, scale
      up feasibility, toxicity, hemodynamics, hemoglobin P50 modification by
      coencapsulation of organic phosphates, liposomal surface modification, and
      storage strategies. In this report, the issue of LEH efficacy following long-term
      storage in the dry state will be addressed. We have shown that hemoglobin,
      liposomes, and LEH may be successfully lyophilized and rehydrated to viable
      states. The modification of the LEH formulation by addition of the carbohydrate
      trehalose results in the successful lyophilization and storage of LEH. In vitro
      characterization of LEH stored in the dry state for up to six months includes
      measurement of oxygen-carrying capacity, liposome size retention, methemoglobin
      production, and the intraliposomal hemoglobin concentration. The in vivo studies
      report on physiological parameters such as circulation persistence, blood
      chemistry, and pathological examination in mice.

PMID- 1391486
TI  - On the interaction of the liposomal membrane with blood components.
AB  - Liposome-encapsulated hemoglobin (LEH) has been shown to be a viable candidate as
      a blood replacement. However, few data have been presented as to how LEH
      interacts with normal blood components. Liposomes were prepared from egg
      lecithin, cholesterol, and dicetyl phosphate or phosphatidic acid, and mixed with
      fresh blood plasma or whole blood. Erythrocyte osmotic fragility, prothrombin
      time (extrinsic coagulation efficiency), activated partial thromboplastin time
      (intrinsic coagulation efficiency), plasma clot stability in urea (fibrin
      stabilizing factor), and clot retraction (platelet activation) were measured.
      Although liposomes were found to bind extensively to erythrocytes, all tests
      indicated that the liposomes had no significant adverse effects, provided that
      normal levels of plasma Ca++ were maintained. The ability of liposomes to absorb
      Ca++ from the plasma was related directly to the amount of dicetyl phosphate or
      phosphatidic acid present and thus, presumably, to the presence of negatively
      charged species in the membrane. The mechanics of deformation of the LEH membrane
      were investigated by encapsulating Hemoglobin S in liposomes. Liposomes
      containing Hemoglobin S were found to sickle when deoxygenated, but not liposomes
      containing normal hemoglobin. Shape analysis of sickled liposomes yielded a
      deforming stress of 10(6) dynes/cm2, about 50 times greater than the reported
      limit for shear elasticity of the erythrocyte membrane.

PMID- 1391487
TI  - Characteristics of polylipid/Hb vesicles (ARC) (in vitro and in vivo test).
AB  - Polylipid/Hb vesicle, which is polymerized phospholipid vesicles (200 nm)
      encapsulating concentrated Hb solution, has been established by us as an
      artificial red cell (ARC). ARC can be easily adjusted to physiological conditions
      (viscosity, density and oncotic pressure etc) as the same of human blood. Our ARC
      has excellent blood compatibility (no effect on coagulation, no hemolysis and no
      red cell aggregation). Neither acute toxicity nor damage of internal organs was
      confirmed. Oxygen transporting capacity was almost the same as human blood, and
      the half life in blood stream was ca. 13 hrs.

PMID- 1391488
TI  - Stability and blood compatibility of polylipid/Hb.
AB  - The Polylipid/Hb vesicle is a new artificial red cell (ARC) based on liposome
      encapsulated Hb. Advantages are derived from the stabilized liposomal bilayer
      membranes, obtained by polymerization of 1,2-bis(2,4-octadecadienoyl)-sn-glycero
      3-phospho choline (DODPC). Furthermore, blood compatibility in vitro are good.

PMID- 1391489
TI  - Intravascular reduction of methemoglobin in plasma of the rat in vivo.
AB  - The formation and reduction of extracellular methemoglobin (metHb) in plasma was
      studied in vivo in conscious rats after isovolemic exchange transfusions with
      polymerized hemoglobin solutions. After exchange transfusions of 40 and 70% of
      the blood volume with hemoglobin solutions, containing less than 6%
      methemoglobin, the methemoglobin level remained below 15%, whereas exchange
      transfusions of greater than 90% resulted in an increase in the metHb level to
      about 30% after 24 hours. The reduction of metHb was studied after exchange
      transfusions with fully oxidized hemoglobin. A gradual decrease in the metHb
      level to 20% was observed after exchanges of 5 or 40%. A higher exchange
      transfusion (70%) resulted also in a decrease in the metHb level but only to
      approximately 40% in 24 hours. In another series of experiments the reduction of
      metHb was studied in vitro with isolated human erythrocytes. Incubation of the
      erythrocytes in the presence of oxidized polymerized hemoglobin (3 g%) resulted
      in a decrease in the percentage of metHb from 91% to 64%. In the presence of 0.2
      mM ascorbic acid the metHb level declined to 22%, suggesting a synergistic
      effect. These results indicate (1) that there is a potent reducing mechanism
      present in blood that can reduce extracellular oxidized polymerized hemoglobin
      and (2) that isolated erythrocytes have a large capacity to reduce extracellular
      metHb, and may also play an important role in the reduction of extracellular
      metHb in vivo.

PMID- 1391490
TI  - Effects of X-linked hemoglobin on in-vitro platelet function.
AB  - The in-vitro function of platelets in 1:1 mixtures of fresh whole blood and 10%
      DBBF alpha-alpha cross-linked hemoglobin in Ringer's acetate buffer was assessed
      by quantitative aggregation after challenge with common agonists and compared to
      the function of platelets in similar dilutions of whole blood in saline. Whole
      blood aggregometry was performed after addition of ADP, collagen, and ristocetin.
      Aggregation was quantified by measuring the change in impedance as drawn on the
      chart recording. No difference in mean impedance change was noted between the
      groups of blood samples which were incubated and tested in the hemoglobin
      solution and those incubated and tested in saline. In addition, incubation and
      stirring of the above mixtures over a period of six minutes without the addition
      of agonists did not result in spontaneous platelet aggregation. We conclude that
      alpha-alpha cross-linked hemoglobin, in the concentration studied, does not
      affect in-vitro platelet function, as measured by whole blood aggregometry.

PMID- 1391491
TI  - Effect of a bovine hemoglobin preparation (SBHS) on the response of two murine
      solid tumors to radiation therapy or chemotherapeutic alkylating agents.
AB  - When tested in mice bearing the Lewis lung tumor with 2, 3, or 4 Gy daily for 5
      days, SBHS produced a dose-modifying factor of 1.6 that was increased to 2.1 with
      carbogen. The addition of SBHS (1.32 gm protein/kg) to treatment with melphalan
      (MEL) resulted in a 2.2-fold increase in the tumor growth delay (TGD). The
      combination of SBHS with carbogen (6 h) produced a 3.6-fold increase in TGD
      compared with MEL alone. The addition of SBHS to treatment with cyclophosphamide
      (CTX) resulted in a 2-fold increase in the TGD. However, the combination of SBHS
      and carbogen was much more effective resulting in a 4.6-fold increase in TGD.
      There was a 1.3-fold increase in TGD with SBHS and CDDP compared with CDDP alone.
      The combination of SBHS and carbogen was a more effective addition to CDDP
      resulting in a 1.9-fold increase in TGD. The addition of SBHS to treatment with
      BCNU increased the TGD produced by BCNU by 1.5-fold. The combination of SBHS/BCNU
      and carbogen resulted in a 2.3-fold increase in TGD over that obtained with BCNU
      alone.

PMID- 1391493
TI  - Ultra-pure polymerized bovine hemoglobin blood substitute: effects on the
      coronary circulation.
AB  - The effects of stroma-free hemoglobin (SFHgb) on the coronary circulation remain
      unclear. An intact canine model utilizing intracoronary adenosine to abolish the
      confounding effect of autoregulation was used to study maximal myocardial oxygen
      delivery during progressive hemodilution with polymerized bovine SFHgb. The
      circumflex coronary artery was instrumented with a flow probe, hydraulic
      constrictor, and proximal and distal catheters for adenosine infusion and distal
      pressure measurement, respectively. This preparation was used to generate
      diastolic coronary pressure-flow relations during maximal vasodilation. Maximal
      coronary conductance and maximal myocardial oxygen delivery were determined in
      two groups of 7 dogs each following hemodilution, first with 6% hetastarch
      (Control), followed by further hemodilution with ultra-pure, polymerized, bovine
      SFHgb. After hemodilution with SFHgb, maximal coronary flow increased slightly
      without evidence of coronary vasoconstriction. Since hemodilution with this
      material increases oxygen carrying capacity, maximal oxygen delivery is greater
      than Control, despite the very low canine hematocrit. These findings suggest: 1)
      SFHgb can provide adequate oxygen delivery to the myocardium despite extreme
      degrees of hemodilution, and 2) in this intact model, there is no evidence of
      adverse coronary vasomotion.

PMID- 1391492
TI  - Role of thromboxane in mediating the intrarenal vasoconstriction induced by
      unmodified stroma free hemoglobin in the isolated perfused rat kidney.
AB  - Unmodified stroma free hemoglobin (SFH) increased renal vascular resistance (RVR)
      from 4.0 +/- 0.2 to 6.9 +/- 0.9 mmHg/ml/min in control isolated kidneys. In
      kidneys obtained from rats pretreated with the thromboxane synthetase inhibitor
      OKY-046 RVR increased from 3.9 +/- 0.3 to 4.8 +/- 0.4 mmHg/ml/min. The percent
      increase in RVR was greater in response to SFH in control kidneys (67 +/- 14%)
      than in OKY-046 treated kidneys (23 +/- 7%)(p less than 0.05). SFH resulted in a
      fall in glomerular filtration rate (GFR) from 0.75 +/- 0.09 to 0.21 +/- 0.04
      ml/min in control kidneys while in kidneys from OKY-046 treated rats GFR fell
      from 0.65 +/- 0.04 to 0.54 +/- 0.06 ml/min. The percent fall in GFR was greater
      in vehicle treated kidneys (69 +/- 8%) as opposed to OKY-046 treated kidneys (19
      +/- 7%)(p less than 0.05). The rate of urinary thromboxane excretion measured
      before the addition of SFH to the perfusate was 52 pg/min in the control group
      and 7 pg/min in the OKY-046 treated group(p less than 0.05).

PMID- 1391494
TI  - Effects of o-raffinose-polymerized human hemoglobin on coronary tone and cardiac
      function in isolated hearts.

PMID- 1391495
TI  - Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) on the endothelium
      dependent relaxation in rat mesenteric arterioles.
AB  - Effects of exchange-transfusion with a modified hemoglobin (pyridoxalated
      hemoglobin polyoxyethylene conjugate; PHP) on diameter of rat mesenteric
      arterioles responding to various vasoactive substances were examined using the
      image-splitter television microscopy method. The mesentery of the anesthetized
      rat was spread over the stage of a microscope and the microvasculature was
      visualized by transillumination. Exchange-transfusion with a 6%PHP solution (30
      ml/kg) was performed and effects of topical application of norepinephrine (NE)
      and acetylcholine(ACh) on diameter of mesenteric arterioles were examined. By
      exchange-transfusion with PHP, NE induced a dose-dependent decrease in diameter,
      while ACh induced a dose-dependent increase in diameter of the arterioles
      preconstricted by NE. There was no difference in vascular responsiveness to ACh
      and NE before and after exchange-transfusion with PHP solution. Results suggest
      that circulating PHP moiety does not exert any action on function of endothelial
      cell to release endothelium-derived relaxing factor (EDRF) in rat mesenteric
      microvasculature in situ.

PMID- 1391496
TI  - Effects of diasprin cross-linked hemoglobin (DCLHb) on cardiac function and ECG
      in the swine.
AB  - The effects of DCLHb on cardiac function were measured in diazepam sedated (2-4
      mg/min) swine. Mean arterial blood pressure (MAP), peak systolic left ventricular
      pressure (IVP), rate of left ventricular pressure development (dP/dt), pressure
      rate product (PRP), cardiac output (CO), and ECG were monitored continuously.
      Hemodynamic parameters were compared during control, DCLHb infusion (40 ml/min),
      one minute balloon occlusion (BO) of the proximal left anterior descending
      coronary artery (LAD) with a 2.5-3.5 F, 20 mm balloon angioplasty catheter, and
      four minute balloon occlusion with DCLHb (BO + DCLHb) perfusion (40 ml/min) of
      the LAD occluded region. Control hemodynamic values were as follows; MAP 91 +/- 6
      mmHg, IVP 102 +/- 6 mmHg, dP/dt 2519 +/- 351 mmHg/min, PRP 15809 +/- 1515
      mmHg.min, and CO 2.72 +/- 0.29 L/min. There was a significant reduction in
      cardiac function with BO as compared to control; MAP 16% decreases, IVP 14%
      decreases, dP/dt 34% decreases, and PRP 40% decreases. In contrast BO + DCLHb
      significantly increased all measurements of cardiac function, with the exception
      of CO as compared to control; MAP 32% increases, IVP 29% increases, dP/dt 20%
      increases, and PRP 19% increases. The S-T segment of the ECG was depressed by a
      significant 0.134 +/- 0.006 mv from control during BO. There was a significant
      decrease 0.093 +/- 0.045 mv in the BO + DCLHb group. These data demonstrate an
      increase in cardiac function and a decrease in S-T segment depression during
      balloon occlusion with DCLHb perfusion. Further studies are needed to define the
      mechanism of action of DCLHb mediated increases in cardiac function.

PMID- 1391497
TI  - Lack of increased cardiac output during hemoglobin hemodilution can be reversed
      with sodium nitroprusside.
AB  - To investigate a possible connection between EDRF or nitric oxide (NO) and the
      unchanged cardiac output (CO) during hemoglobin-hemodilution we infused
      nitroprusside (NP) in eight Hb-diluted dogs (Hct approximately 20%). Normal
      hypotensive doses of NP were not effective and supranormal doses (133.0
      micrograms/kg/min) were needed to induce even a modest decrease in mean AoP
      (approximately 25 mmHg). With these NP doses, cardiac output increased 177%,
      diastolic AoP (afterload) decreased 30%, while systolic AoP and LVEDP (preload)
      were unchanged. Heart rate, LV contractility (pressure-volume function) and blood
      volume were not changed throughout the study. Normally, NP alone decreases both
      preload and afterload resulting in unchanged CO. In the Hb + NP dogs, CO
      increased because only afterload decreased suggesting a selective effect of Hb on
      venous and arterial smooth muscle relaxation. In hemodilution with nonhemoglobin
      colloids, CO increases primarily because the diluted blood offers less viscous
      resistance to ventricular ejection. It appears that in order for cardiac output
      to increases in the presence of Hb, some decrease in arteriolar resistance is
      needed, presumably to unmask the effects of reduced viscosity. These results
      suggest the unchanged CO during Hb-dilution is related to a selective effect of
      Hb on venous and arteriolar nitric oxide (EDRF) function.

PMID- 1391498
TI  - Effects of modified hemoglobin solutions on the isolated rabbit heart.
AB  - The effects of modified hemoglobin (Hb) solutions on the coronary vasculature
      were studied. Hearts were perfused according to Langendorff with constant flow of
      Tyrode solution. The solutions studied were stroma- free Hb, prepared by lysis of
      red blood cells in water (SFHb-lys), or prepared by swelling of red blood cells
      in hypotonic phosphate buffer (SFHb). The increase in coronary vascular
      resistance at a dose of 200 mg Hb/dl was 68% for SFHb-lys and 13% for SFHb,
      respectively. Addition of the modified Hb solutions HbNFPLP and polyHbNFPLP
      produced an increase in coronary resistance of 11% and 8%, respectively. The left
      ventricular developed pressure (LVDP) (control value 72 +/- 12 mm Hg) increased
      by 18 and 12 mm Hg, respectively, for a dose of 250 mg Hb/dl. When HbNFPLP was
      converted to its met-Hb form the increase in LVDP was reduced to 3 mmHg and the
      increase in perfusion pressure to 6 mm Hg. We conclude that elimination of
      stromal contamination from Hb solutions can diminish vasoconstrictor effects. The
      increase in cardiac pressure development and in coronary vascular resistance
      found for dilute modified Hb solutions is partly due to an improved oxygen
      transport to the heart.

PMID- 1391499
TI  - Effect of stabilized hemoglobin as a component of cardioplegia on warm ischemic
      heart.
AB  - Stabilized hemoglobin was utilized as a component of cardioplegia in isolated rat
      heart. While oxygen consumption and heart function was better preserved in long
      term after reperfusion, damage from reperfusion injury was suspected and reversed
      in part by diltiazem.

PMID- 1391500
TI  - Heart protection by cardioplegic solutions containing oxyhemoglobin pretreated by
      carbontetrachloride and freeze-drying with sucrose.
AB  - A technologically improved variant of native stroma-free oxyhemoglobin (SFH)
      pretreated by carbontetrachloride and freeze-drying with 240 mM sucrose were
      reconstituted in a properly diluted ionic solution to reach the final
      concentration of 66 g oxyhemoglobin/L, osmolality 280-320 m0sm and pH 7.4.
      Cardioplegia of isolated rat heart was induced and maintained by this solution
      without recirculation for 3 h at 20 degrees C prior to heterotopic allo
      transplantation of the graft. Evaluation of the survival and performance of each
      graft after 24 h and extent of tissue necroses indicated that the given
      standardly produced SFH variant ensured reproducible heart preservation from
      ischemic and reperfusion injury similarly as did the renown crystalloid
      cardioplegic solution CUSTODIOL.

PMID- 1391502
TI  - Systemic hemodynamic and renal effects of unmodified human SFHS in dogs.
AB  - Isovolumic exchange transfusion (25% of total estimated blood volume) was carried
      out in the anesthetized dogs using 9 g/dl of unmodified human stroma-free
      hemoglobin solution (SFHS). The objective was to determine the systemic
      hemodynamic, blood distribution and renal effects of SFHS over a 2-3 hour period
      post-exchange. At 30 minutes after the exchange, blood pressure rose from 114 +/-
      117 to 133 +/- 22 mmHg, but this rise was not sustained thereafter. Mean
      pulmonary arterial blood pressure rose from 8 +/- 3 to 13 +/- 2 mmHg, and
      remained above the pre-exchange level up to 3 hours post-exchange. Cardiac output
      remained within normal limits. Significant flow-increments were seen at 30
      minutes in heart, brain, liver, gut, and kidney, but these were also not
      sustained. A fall in glomerular filtration rate (GFR) occurred after the exchange
      and remained below the pre-exchange level. A reduction in urine flow at 150
      minutes post-exchange was observed and was accompanied by a reduction in urinary
      electrolyte excretion. The findings suggest that the initial effects of the
      administration of unmodified stroma-free hemoglobin solution are those of
      peripheral vasoconstriction which does not appear to significantly restrict flow
      to the vital organs, such as heart and brain. Unmodified hemoglobin was found to
      cause a decrease in renal function.

PMID- 1391501
TI  - Effects of pyridoxalated hemoglobin polyoxyethylene conjugate(PHP) and stroma
      free hemoglobin(SFH) on pulmonary vascular responsiveness to various vasoactive
      substances in isolated perfused rat lungs.
AB  - Pulmonary vascular responsiveness to norepinephrine(NE), angiotensin-II (ANG-II),
      acetylcholine(ACh) and nitroglycerin (NG) was examined in isolated perfused rat
      lungs. The lungs were perfused with pyridoxalated hemoglobin polyoxyethylene
      conjugate (PHP), a newly introduced modified hemoglobin, stroma free hemoglobin
      (SFH) or hydroxyethyl starch (HES) at a constant flow rate. Perfusion pressure
      (PP) and intra-tracheal pressure (ITP) were measured. Effects of intrapulmonary
      arterial injection of NE, ANG-II, ACh and NG on PP were examined. NE and ANG-II
      produced a dose dependent increase in PP in all groups. The response to NE in PHP
      or SFH perfused group was significantly greater than that in HES-perfused group.
      ACh induced a dose dependent decrease in PP in HES and PHP groups, while in the
      SFH group, ACh produced a dose dependent increase in PP. NG produced a dose
      dependent decrease in all groups. Results showed that stroma free hemoglobin
      (SFH) inhibits relaxation induced by endothelium-derived relaxation factor
      (EDRF), but PHP dose not exert inhibitory action on vascular relaxation induced
      by EDRF.

PMID- 1391503
TI  - Effects of pyridoxalated hemoglobin polyoxyethylene conjugate(PHP) on renal
      circulation in isolated perfused rat kidneys.
AB  - We examined effects of perfusion of the kidney with pyridoxalated hemoglobin
      polyoxyethylene conjugate(PHP) solution on rat renal vascular responsiveness to
      norepinephrine(NE), angiotensin-II (AN-II), acethylcholine(ACh) and
      nitroglycerine(NG). The rat kidney was perfused with hydroxyethylstarch(HES) or
      PHP at a constant flow rate, using a pump. Perfusion pressure was monitored by a
      pressure transducer. Changes in PP induced by NE, AN-II, ACh and NG was examined.
      NE and AN-II applied intra-arterially induced a dose-related increase in PP in
      rat kidney perfused with both HES and PHP perfused groups. ACh and NG produced a
      dose dependent decrease in PP in both HES and PHP-perfused groups. There was no
      significant difference in response to ACh and NG between both groups. Results
      suggests that in rat vascular beds, PHP dose not interfere vascular relaxation
      caused by release of EDRF induced by ACh.

PMID- 1391504
TI  - Artificial blood and extracorporeal circulation (ECC).
AB  - To investigate a possible clinical use in ECC of artificial blood (AB) by means
      of a stroma free, polymerized and pyridoxylated hemoglobin a feasibility study
      was performed. Group I (5 calves) served as control. Group II (5 calves) received
      2000 ml of a mixture of one part AB and one part Ringer's solution, group III (5
      calves) 2000 ml of AB as priming solution. Blood samples were taken
      preoperatively, at 6 h, 24 h and then weekly up to 1 month. All animals survived
      and could be weaned from the ventilator immediately after the operation. Total
      hemoglobin was 10.6 before and 9.5 g/dl 12 h after the operation in mean in the
      group I and 11.5 and 11.9 for group II and III. Aortic mean pressure was
      increased in group II/III from preoperatively 105/95 mmHg to 124/135 mmHg after
      the end of cardio pulmonary bypass (CPB). The pulmonary vascular resistance
      increased in group II/III from 92/52 to 214/264 dyn*s*cm-5 in mean. This could
      not be observed in group I. Pulmonary resistance correlated with the
      concentration of free plasma hemoglobin.

PMID- 1391506
TI  - Effect of polymerization on clearance and degradation of free hemoglobin.
AB  - In the present study we investigated the mechanism of prolongation of the plasma
      retention of free hemoglobin by polymerization. Polymerization of
      intramolecularly crosslinked hemoglobin with glutaraldehyde yields a mixture of
      large polymers, small polymers and monomers. In exchange transfusion experiments
      in rats we analyzed plasma samples by gel filtration to determine the clearance
      of polymers of different size. A positive correlation was found between polymer
      size and vascular retention. Furthermore, the clearance of large polymers
      appeared to be highly dose-dependent: after 20% and 70% exchange transfusions, we
      observed for large polymers a plasma half-life of 12 and 26 hours, respectively,
      whereas the half-life for 64 kD monomers was 4 hours in both cases. The
      degradation of hemoglobin was followed by measuring the bilirubin excretion. The
      infused heme was recovered as bilirubin within 72 hours. The delay between the
      disappearance of free hemoglobin from the plasma and the recovery as bilirubin
      was about six hours and was not affected by polymerization or dose. We conclude
      that polymerization prevents the operation of certain clearance mechanisms, while
      still allowing a route of clearance that is easily saturated. The intracellular
      degradation of heme into bilirubin is not affected by the modifications of
      hemoglobin and is not easily saturated.

PMID- 1391505
TI  - The role of the kidneys in the excretion of chemically modified hemoglobins.
AB  - Stroma-free hemoglobin (SFHb) can be chemically modified to prolong the
      intravascular retention (prevent renal filtration), and to improve oxygen
      delivering capability for use as a red cell substitute. Hb derivatives
      radioactively tagged with tritium [3H] or 14C were used to study their metabolic
      fate following clearance from the circulation. Fully conscious, chronically
      cannulated rats were treated by exchange transfusion (ET). Hb solutions tested
      were: PLPHb (Hb monovalently reacted with pyridoxal 5'-phosphate); HbXL (Hb
      crosslinked beta-beta with 2-nor-2-formylpyridoxal 5'-phosphate, or with bis
      pyridoxal tetraphosphate); alpha alpha Hb (Hb cross-linked between the alpha
      chains using bis-3,5-dibromosalicyl fumarate); and polyHb (polymerized with
      glutaraldehyde or o-raffinose). Plasma retention (T1/2) was significantly
      affected by dose and the degree of cross-linking. Urine flow rates all increased
      transiently above normal. In rats treated with any 64 kDa interdimerically cross
      linked Hb, mild hemoglobinuria was evident and kidney tissue had the highest
      label concentration at all time points (1, 5, 10, 24, 48 hr, 7 d, and 14 days
      post-ET). For polymerized Hb derivatives, the amount of radioactivity in urine
      and kidneys was inversely related to the MW of the polyHb molecules. In all rats,
      regardless of the Hb derivative tested, the majority of radioactivity (dpm's) was
      excreted in urine. About 75% of all renal excretion of radioactivity occurred
      from 12-60 hours post-ET. This provided evidence that catabolism of cross-linked
      Hb's began early, and that the kidneys are primarily responsible for excreting
      smaller degradation fragments.

PMID- 1391508
TI  - Biodistribution studies of liposome encapsulated hemoglobin (LEH) studied with a
      newly developed 99m-technetium liposome label.
AB  - A new method has been developed to label preformed liposomes with 99m-Technetium
      (99mTc) using hexamethylpropylenamine oxime (HMPAO). 99mTc is an ideal isotope
      for performing non-invasive dynamic biodistribution studies. This labeling method
      results in a high labeling efficiency (greater than 95%) and is stable as
      determined by both in vitro and in vivo studies. In vitro studies indicated that
      glutathione encapsulated in the LEH is important in the labeling process with
      99mTc-HMPAO. In vivo studies with LEH were performed on 7 rabbits with dynamic
      scintigraphic 1 minute images performed from 1-120 minutes. Delayed images were
      performed at 20 hours followed by sacrifice and organ counting. Dynamic images
      reveal a gradual deposition of the LEH in the liver and spleen. Twenty hour
      biodistributions revealed 50% of the LEH remaining in the blood, 15% in the
      liver, 14% in the spleen, 3% in lungs, 3% in muscle with trace amounts in the
      brain, kidneys, and heart. Doses per gram were highest in the spleen with 12.5%
      of the injected dose per gram of spleen vs. 0.2% per gram of liver. This labeling
      technique is an effective method for non-invasively monitoring dynamic changes in
      liposome biodistribution and can be used to study the effects of various liposome
      modifications on biodistribution.

PMID- 1391507
TI  - Intravascular circulation and distribution of human 51Cr-DBBF stroma-free
      hemoglobin.
AB  - Male B6C3HF1 mice were infused with 51Cr-labeled DBBF (bis 3,5-dibromosalicyl
      fumarate) crosslinked stroma-free hemoglobin (SFH). The intravascular halftime
      (T50) of the DBBF-SFH, determined from plasma hemoglobin levels, was 0.5 hours in
      the first 10 minutes and 4.3 hours during the next 50 minutes. At 24 hours, less
      than 5% of the DBBF-SFH remained. Elution of 51Cr was reflected in a lower T50
      determined from the radioactivity levels: during the first 10 minutes the T50 was
      0.3 hours; in the next 50 minutes it was 1 hour. The radioactivity sequestered in
      each organ in the first hour following DBBF-SFH infusion was as follows: 11.2% of
      the infused radioactivity was in the skin, 11.4% in muscle, 9.1% in the skeleton,
      and 5% in the liver. After 24 hours, the percentages in skin, muscle, skeleton
      and liver were 15.4, 10.3, 16.6 and 6.7% respectively. The percentage of infused
      radioactivity in the gastrointestinal tract and kidney at 1 hour and 24 hours
      ranged from 3.5 to 5.5%. Less than 0.4% was found in the spleen and lung. At 24
      hours, 25% of the radioactivity was recovered in urine and 3% in feces.

PMID- 1391509
TI  - Interactions of liposome encapsulated hemoglobin and phosphate buffer liposomes
      with neutrophilic granulocytes and plasma.

PMID- 1391510
TI  - Effects of liposome encapsulated hemoglobin on the reticuloendothelial system.
AB  - The effects of different doses (4, 10, and 25%) of liposome encapsulated
      hemoglobin (LEH) were measured on the Reticuloendothelial System (RES) and
      Kupffer cells (KC) by i) colloidal carbon clearance in the rat in vivo and in the
      isolated perfused liver, ii) magnetometry, and iii) histological analysis. At the
      highest dose, in vivo carbon clearance rates (k) were half the rate as in
      controls at 2 and 12 hours post-treatment. By 24 hours post-treatment clearance
      rates were at control levels. Empty liposomes (LIP) caused a 2-fold decrease in k
      at 2 hours only. With both LEH and LIP, the effects were less severe when rats
      were given the lower doses. Magnetometric studies showed a decrease in KC
      phagosomal motion in the LEH-treated (25%) rats at 2 and 24 hours that returned
      to control levels at 2 weeks. Perfused livers from rats treated with a low dose
      of LEH cleared carbon at the same rate as LIP and Krebs Ringer Bicarbonate (KRB)
      controls. Histological examination showed minimal tissue damage in all test
      groups. Thus, LEH and LIP have some short-term deleterious effects on KC and the
      RES probably due to RES blockade rather than cellular damage.

PMID- 1391511
TI  - A double (exchange transfusion-carbon clearance) model for testing post
      resuscitation reticuloendothelial function.
AB  - A double exchange transfusion-double carbon clearance method was evaluated for
      assessing reticuloendothelial (RE) function following exchange transfusion with
      hemoglobin solutions. Fifty percent of estimated blood volume (3% body weight)
      was withdrawn from anesthetized Sprague-Dawley rats and isovolumically replaced
      with shed blood (SB, control), lysed shed blood (LB, pos. control), human stroma
      free hemoglobin solution (SFH), or polyhemoglobin solution (PHS). Thirty minutes
      after the exchange transfusion, colloidal carbon was injected intravenously and
      its vascular clearance followed for 1 hour. Then, the 50% exchange transfusion
      was repeated and the second carbon clearance measured. The intravascular carbon
      clearance constants, K, and clearance half-times, T1/2, were calculated and
      compared. No apparent differences in RE function were seen among the groups after
      the initial exchange transfusion. However, following the second exchange
      transfusion significant (P less than 0.05) slowing of carbon clearance was
      observed in lysed blood treated animals. The RE function of SFH or PHS treated
      animals were not different (P less than 0.05) from that of SB animals. A double
      exchange transfusion-double carbon clearance method seems to reveal changes in RE
      function that are not apparent after a single exchange transfusion and clearance
      test.

PMID- 1391512
TI  - Clearance of differentially labelled infused hemoglobin and polymerized
      hemoglobin from dog plasma and accumulation in urine and selected tissues.
AB  - Pyridoxalated hemoglobin polymerized with glutaraldehyde has been proposed as a
      hemoglobin based blood substitute. The preparations contain significant amounts
      of unpolymerized hemoglobin. We have prepared polymerized pyridoxalated
      hemoglobin labelled with 14C by reductive methylation free of unpolymerized
      hemoglobin and pyridoxalated hemoglobin labelled with 3H by reductive methylation
      to compare the handling of the two forms after infusion into dogs. Four dogs were
      examined sequentially. After three hours, 52.4 +/- 8.9% of the 3H label had
      disappeared from plasma whereas 21.7 +/- 5.8 of the 14C label had disappeared.
      The decrease of both labels occurred in a very close to linear fashion over the
      time period examined. From radioactivity in collected urine, it was calculated
      that 30.7 +/- 6.3% of the 3H and 9.0 +/- 2.7 of the 14C that had been cleared
      from plasma appeared in urine. The ratio of the specific radioactivity in tissue
      to the specific radioactivity of plasma indicated that extravascular accumulation
      of 3H label from unpolymerized hemoglobin occurred in kidney, heart and liver,
      with the kidney cortex exhibiting a very high concentration of the label. The
      specific radioactivity of both 3H and 14C label in liver suggested the
      substantial involvement of the reticuloendothelial system in the removal of both
      unpolymerized and polymerized hemoglobin from the circulation.

PMID- 1391513
TI  - Hepatic reticuloendothelial function following resuscitation with hemoglobin
      solutions.
AB  - Red cell substitutes could lead to depressed reticuloendothelial (RE) particulate
      clearance function. This hypothesis was tested using an animal model of
      hypovolemia-resuscitation. Anesthetized male Sprague-Dawley rats were subjected
      to 50% blood volume hemorrhage followed by isovolumic replacement with stroma
      free hemoglobin (SFH, 7 gHb/dl), polyhemoglobin (PHS, 14 gHb/dl), or shed blood
      (SB). At 30 min post-transfusion, the liver was isolated and perfused with
      colloidal carbon. Hepatic RE function was assessed from the carbon clearance
      kinetics. In separate experiments, the hepatic Kupffer cells were isolated and
      cultured from rats that were previously hemorrhaged and transfused with normal
      saline solution. The cultured Kupffer cells were incubated with SFH or bovine
      albumin (ALB) and their phagocytic function assessed in-vitro. The hepatic carbon
      clearance following exchange transfusion with hemoglobin solutions was not
      significantly altered as compared to shed blood controls (P greater than 0.05).
      Similarly, phagocytic function of hemoglobin treated Kupffer cells was not
      significantly different (P greater than 0.05) from that of ALB treated cells.

PMID- 1391514
TI  - Oxygen delivery from fluorocarbon emulsions--aspects of convective and diffusive
      transport.
AB  - Perfluorocarbons (PFCs) deliver oxygen due to their physical characteristics and
      the convective delivery to tissues; this has been amply demonstrated in numerous
      animal models and in clinical trials. PFC emulsions have also been used for organ
      perfusion and augmentation of oxygenation to cell cultures. By reason of their
      small particle size, PFC emulsions penetrate collateral capillaries of an
      ischemic microcirculation, both supplying oxygenation and possibly restoring
      flexibility of acidotically stiffened erythrocytes by reinstituting aerobic
      metabolism. There is also evidence that PFCs can augment tissue oxygenation by
      increasing oxygen solubility in the plasma phase of blood; this improves
      diffusion gradients between plasma and tissues even at relatively low doses of
      PFC. This hypothesis is supported by the ability of PFCs to increase oxygen
      tensions in tissues such as blood, brain, liver, kidney, pancreas, skeletal
      muscle, retina etc. PFCs can also on occasions increase critical oxygen
      extraction coefficients and should therefore be effective in supporting oxidative
      metabolism in states of extreme cardio-respiratory insufficiency. This theory
      represents a new concept in oxygen delivery and may define a new class of
      therapeutic agents that can improve tissue oxygen supply in various pathological
      states involving low oxygen delivery and ischemia.

PMID- 1391515
TI  - On the perfluorocarbon emulsions of second generation.
AB  - Perfluorocarbon-emulsions of second generation were prepared by means of new
      perfluorocarbons (F-dimorpholines, F-dipiperidines and F-cyclohexylmorpholine),
      acting both as oxygen carriers and as interfacial active compounds (IFACs). The
      stabilizing effect of these IFACs is interpreted and a new theory is introduced.
      Also new classes of fluorosurfactants were synthesized and tested for
      biocompatibility. In PFC mixtures compounds of the type RFRH (RF = CmF2m + 1, RH
      = CnH2n + 1) are acting as IFACs but also as anchor-groups for lipophilic
      surfactants.

PMID- 1391517
TI  - Phospholipid vesiculated fluorocarbons--promising trend in blood substitutes.
AB  - Dispersions of fluorocarbons (PFC's) made with phospholipids have unusual
      properties, e.g. very high stability, due to the formation of thermodynamically
      stable vesicles. They can be used for high PFC concentrations as well as e.g. for
      ESR imaging.

PMID- 1391516
TI  - Stability and stabilization of fluorocarbon emulsions destined for injection.
AB  - The factors that have an impact on the stability, and the mechanisms of
      degradation of fluorocarbon emulsions suited for intravascular use, are briefly
      reviewed. Various ways of prolonging shelf stability are discussed. The
      effectiveness of perfluoroalkylated surfactants and/or co-surfactants as
      stabilizers is demonstrated. New means of stabilizing fluorocarbon-in-water
      emulsions using molecular dowels are presented.

PMID- 1391518
TI  - Perfluoroalklylated phospholipids as surfactants and co-surfactants forinjectable
      fluorocarbon emulsions.
AB  - Highly fluorinated phospholipids were investigated as sole surfactant, and as co
      surfactant with egg yolk phospholipids (EYP), in the formulation of 50% and 100%
      w/v perfluorodecalin emulsions. The surfactant's capability to stabilize such
      emulsions improves with the length of the perfluoroalklylated tail and with the
      increase of its relative weight in the hydrophobic chain. As sole surfactant, 2,
      which has the longest fluorinated tail has the highest efficacy. As co-surfactant
      with EYP, a strong stabilizing effect is found when the total hydrophobic chain
      length is adjusted to the EYP membrane's thickness, which is the case of 1.
      Dispersions of the F-phospholipids do not modify cell growth and viability and
      show no hemolytic activity on human red blood cells at concentrations in the 60
      100g/L range. Acute toxicity tests in mice indicate - i.v. DL50 greater than 2.75
      g/Kg body wt.

PMID- 1391519
TI  - Development of highly fluid, concentrated and stable fluorocarbon emulsions for
      diagnosis and therapy.
AB  - A challenging aim in developing injectable fluorocarbon emulsions is to combine
      good flow characteristics (especially at low shear rates) with the high
      fluorocarbon concentration required for high oxygen delivery or effective
      contrast in imaging, long shelf life, and biological acceptability. A good
      balance of these sometimes conflicting objectives has been achieved with 90% w/v
      concentrated emulsions of various fluorocarbons, including the radiopaque oxygen
      carrier perfluorooctylbromide (PFOB, perflubron). The sterile emulsions have
      viscosities of about 20 cPs at a shear rate of 1 sec-1; the viscosity decreases
      rapidly with fluorocarbon concentration, and at 60% w/v the viscosity is less
      than that of human blood. The emulsions are suitable for injection as prepared,
      and are stable unfrozen for over a year.

PMID- 1391520
TI  - Telomeric THAM-derived perfluoroalkylated surfactants for fluorocarbon emulsions.
AB  - New fluorophilic and hydrophilic, cost efficient telomeric surfactants derived
      from tris(hydroxymethyl)acrylaminomethane were synthesized in 2 steps in 80%
      yield with respect to the perfluoroalkylated telogen. They demonstrate better
      ability to emulsify fluorocarbons than Pluronic f-68. The biological tolerance of
      these new surfactants is remarkable, the perfluorohexyl derivative was tolerated
      at doses of 4g/kg bw after i.v. injection in mice. None of the perfluoroalkylated
      THAM derivatives induces hemolysis of human red blood cells at concentrations up
      to 200g/l in physiological solutions.

PMID- 1391521
TI  - Stabilization of perflubron emulsions with egg yolk phospholipid.
AB  - Egg Yolk Phospholipid(EYP) has been used extensively as the primary surfactant in
      parenteral fat emulsions for many years. The simplicity, functionality and
      physiologic tolerance of EYP has contributed greatly to its success in the
      intravenous emulsion arena. The mechanism of stabilization in triglyceride
      emulsions is well understood; however, this is not the case with perfluorocarbon
      emulsions. Interfacial models, as well as emulsion stability studies, have been
      conducted utilizing EYP of varied composition in order to derive a
      structure/function relationship. Our studies indicate that minor components,
      total unsaturation, acyl chain length and presence of charged species have
      significant impact on the functional properties of EYP and the subsequent
      stability of the emulsion product. These findings contribute to our ability to
      design and manipulate natural surfactants with superior properties for use in
      medical applications of perfluorocarbon emulsions.

PMID- 1391523
TI  - Terminal sterilization of perfluorocarbon (PFC) emulsions: difficulties and
      possible solutions.

PMID- 1391522
TI  - Application of computer-based experimental design to optimization of processing
      conditions for perfluorocarbon emulsion.
AB  - Response surface methodology was applied during process optimization of a
      parenteral emulsion formulation containing perfluorocarbon (PFC). E-Chip, a
      computer software program, was used to design and analyze the optimization
      experiments. The levels of eight process variables of interest were varied: pre
      emulsification temperature and mixing time, mixer speed, generator type, rate of
      PFC addition, homogenization temperature, pressure and number of passes.
      Dependent variables evaluated included emulsion median diameter, viscosity and
      percent unemulsified PFC. A predictive model describing the relationship between
      the dependent and process variables was developed. Median diameter of the
      emulsion was affected significantly by homogenization temperature and pressure,
      and marginally by the rate of addition of the PFC. Viscosity was not influenced
      by any of the process variables. Percent unemulsified PFC was slightly influenced
      by the number of homogenization passes. The model was then used to set optimum
      process conditions.

PMID- 1391524
TI  - Particle size distribution of concentrated perfluorocarbon emulsions by
      sedimentation field flow fractionation.
AB  - Alliance Pharmaceutical Corp's concentrated perflubron (perfluorooctylbromide;
      PFOB) emulsions are being developed for several medical applications.
      Sedimentation Field-Flow Fractionation (SdFFF) can provide accurate particle size
      distribution data when properly calibrated for those emulsions. Since no suitable
      particle standards are available with the proper density (approximately 1.9 g/cc)
      and size range (diameter = 0.1-1.0 microns), calibration of the mass distribution
      was done by comparing the SdFFF detector signal with the actual mass of
      perflubron extracted from fractions eluted at successive time points and measured
      by GC. The calibrated mass distribution can then be used to calibrate other
      instruments such as the photosedimentation instruments used for routine quality
      assurance measurements.

PMID- 1391525
TI  - Drop size stability assessment of fluorocarbon emulsions.
AB  - The aging of fluorocarbon emulsions prepared with natural egg yolk phospholipids
      (EYP) has been studied and a linear variation (r2 greater than 0.95) of the mean
      average volume of the droplets with time has been observed. The slope of the
      experimental lines, called "Stability Parameter, S" can thus be taken as a
      representation of the rate of aging of the emulsions. Examples are given of use
      of parameter S to assess the effect of formulation and processing parameters on
      the stability of diverse fluorocarbon emulsions. S is a useful tool to compare
      emulsions and ascertain any factors of stabilization/destabilization.

PMID- 1391526
TI  - Rheology of concentrated perfluorocarbon emulsions.

PMID- 1391527
TI  - Use of perfluorochemical emulsions in cancer therapy.
AB  - Over the past 10 years, the use of perfluorochemical emulsions (PFCE) and
      carbogen or oxygen breathing has been explored as an adjuvant to radiation
      therapy and/or chemotherapy in the treatment of solid tumors. The rationale for
      the use of PFCE and oxygen breathing in this therapeutic setting is that solid
      tumor masses contain areas of hypoxia which are therapeutically resistant. Since
      x-rays and many chemotherapeutic agents require oxygen to be maximally cytotoxic
      and most normal tissues are well-oxygenated, the additional oxygen put in
      circulation by the PFCE should not increase the normal tissue toxicities produced
      by the various therapies. The largest body of preclinical work and all of the
      clinical studies in cancer conducted with PFCE, thus far, have been done with
      Fluosol-DA, 20%. Oxygen microelectrode studies have confirmed increased
      oxygenation in previously hypoxic tumor regions after the administration of
      Fluosol-DA and carbogen breathing. The preclinical studies have shown very
      positive effects with single dose and fractionated radiation in several rodent
      solid tumor models. Many widely used anticancer drugs including antitumor
      alkylating agents and adriamycin are enhanced by PFCE and carbogen breathing for
      longer time periods (6 h). More recently, several experimental concentrated PFCE
      preparations have become available and work with these is actively under way in
      several laboratories. Clinical studies with radiation and four or five
      chemotherapeutic drugs as single agents have indicated that Fluosol-DA followed
      by oxygen breathing can be administered safely in a variety of cancer therapeutic
      settings. Further clinical studies with Fluosol-DA are planned.

PMID- 1391528
TI  - Preclinical evaluation of Oxygent as an adjunct to radiotherapy.
AB  - These studies examine the potential value of a concentrated emulsion of
      perfluorooctylbromide (perflubron; Oxygent, Alliance Pharmaceutical Corp.) as an
      adjunct to radiotherapy. The effects of Oxygent on solid tumors were examined
      using EMT6 mammary tumors in BALB/c mice and BA1112 rhabdomyosarcomas in WAG/rij
      rats. Treatment with Oxygent plus O2, carbogen (95% O2/5% CO2), or hyperbaric
      oxygen (HBO) increased the effects of radiation on the tumors. Analyses of tumor
      cell survival curves and measurements of intratumor pO2 showed that this
      potentiation reflected an increase in the proportion of well-oxygenated tumor
      cells. Neither treatment of the animals with carbogen, O2, or HBO alone nor
      treatment of air-breathing rodents with Oxygent produced changes of similar
      magnitude. Treatment with a vehicle emulsion containing all the components of
      Oxygent except the perflubron did not alter tumor radiosensitivity, showing that
      tumor radiosensitization required the oxygen-transporting perfluorocarbon, and
      did not result from any biologic or physiologic effects of other components of
      the emulsion. These studies also examined the effects of Oxygent on the radiation
      responses of mouse skin and bone marrow. Oxygent selectively increased the
      radiation sensitivity of tumors relative to these normal tissues, thereby
      increasing the therapeutic ratio and producing therapeutic gain. Oxygent appears
      to warrant further testing as an adjunct to cancer therapy.

PMID- 1391529
TI  - Enhancement by perflusion emulsion (Oxygent) and carbogen breathing of the tumor
      growth delay of the FSaIIC fibrosarcoma after treatment with antitumor alkylating
      agents.
AB  - Many anticancer drugs require oxygen to be cytotoxic, or are selectively
      cytotoxic toward cells under oxygenated conditions. The effects of the dilute
      perfluorochemical emulsion Fluosol-DA with a wide variety of chemotherapeutic
      agents have been explored; however, it has not been possible to determine the
      optimal level of circulating perfluorochemical emulsion with anticancer drugs
      because the volume of Fluosol that may be administered in limited. Using a
      concentrated 90% Perflubron emulsion, Oxygent, a wide range of perfluorochemical
      emulsion doses have been examined in combination with melphalan, cyclophosphamide
      and BCNU in a murine solid tumor model. When Oxygent was administered by
      injection i.v. just prior to the injection of melphalan (10 mg/kg), the greatest
      tumor growth delays were obtained with Oxygent levels between 4 and 12 g PFC/kg.
      With each of these drugs the greatest tumor growth delays were obtained when the
      drug was prepared in the emulsion and the combination injected i.v. In each case,
      each dose of drug was followed by 6 h. of breathing carbogen.

PMID- 1391530
TI  - Enhancement of fractionated radiation therapy by an experimental concentrated
      perflubron emulsion (Oxygent) in the Lewis lung carcinoma.
AB  - The concentrated Perflubron emulsion, Oxygent, in combination with breathing a
      95% oxygen atmosphere, significantly enhanced the response of the murine Lewis
      lung carcinoma to fractionated radiation therapy. Administration of 4 to 12 g
      PFC/kg was most effective if administered prior to each x-ray fraction, however,
      alternated day and even once weekly administration of 8 or 12 PFC/kg and 95%
      oxygen breathing with each x-ray fraction resulted in significant improvements in
      tumor growth delay.

PMID- 1391531
TI  - Effect of emulsion concentration on biodistribution of perflubron in tumor
      bearing mice.
AB  - Perflubron (perfluoroocytlbromide, PFOB) emulsion concentrations of 100%, 90%, or
      60% w/v were administered to mice with and without 3 types of murine malignant
      tumor implants, and the distribution in blood, tumor, lung, liver and spleen were
      studied 48 hours after a dose of 10 or 3 g/Kg of PFOB. The most important changes
      were seen in the blood where the PFOB concentration [PFOB] was decreased in tumor
      bearing mice (TBM). Blood [PFOB] was also decreased in TBM and normal mice (NM)
      that received the 60% emulsion. Liver [PFOB] was increased in TBM. Lung [PFOB]
      was directly proportional to the emulsion concentration with the 10g/Kg dose. No
      major differences were seen in the biodistribution between the 100% and 90%
      emulsions using 10g/Kg, in spite of differences in composition and manufacturing
      history.

PMID- 1391532
TI  - Cyclooxygenase inhibition with ibuprofen: effect on biodistribution of perflubron
      emulsions in mice with mammary tumor.
AB  - The biodistribution of Perflubron (perfluorocytylbromide, PFOB) was studied by
      infusing 10 or 3 g/Kg doses of 90% and 100% w/v emulsions into Balb C mice with
      and without malignant mammary tumor implants. PFOB concentrations were measured
      in blood, liver, spleen, lung and tumor, and X-rays were taken 48 hours after
      infusion. Ibuprofen (IBU) was given intraperitoneally 10 mg/Kg dialy for 3 days
      to study the effects of cyclooxygenase blockade. The results showed that the
      blood [PFOB] in tumor-bearing mice (TBM) was only 3.6% of that measured in normal
      mice (NM), and the liver [PFOB] was increased by 59%. The lung [PFOB] increase
      with IBU therapy in NM was highly significant. IBU therapy resulted in a 98% and
      468% increase in blood [PFOB] in normal and TBM, respectively. Smaller but
      statistically significant changes occurred in blood [PFOB] with saline and sham
      injections. Tumor [PFOB] was lower by 17% (P = .028) in mice treated with IBU.
      Smaller decreases were seen with saline and sham injections but did not achieve
      statistical significance. In conclusion, the presence of this malignant tumor
      resulted in changes that might influence the usefulness of PFOB as a contrast
      agent and as an adjuvant for radiation and chemotherapy. This study shows that
      cyclooxygenase inhibition significantly modified the pharmacodynamics of PFOB
      emulsions in blood, tumor and lung. The changes seen in the saline placebo and
      sham category were attributed to stress from procedures.

PMID- 1391534
TI  - Quantitation of perfluorocarbon blood substitutes in tissues using F-19 magnetic
      resonance spectroscopy.
AB  - F-19 Magnetic Resonance Spectroscopy (MRS) has been used to quantitate the
      biodistribution of perfluorocarbon (PFC) blood substitutes in porcine tissues
      following intraperitoneal administration of a 20% w/v perfluorotributylamine (FC
      43) based emulsion. PFC tissue concentrations were determined for spleen, liver
      and lung tissues from juvenile pigs ranging in weight from 12 to 15 kg. Typical
      average values (mmoles FC-43/gram tissue) ranged from 0.23-0.39 for spleen; 0.09
      0.13 for liver; and 0.09-0.12 for lung. A description of this spectroscopy based
      quantitation technique will be presented. F-19 MRS is a specific, rapid, and
      accurate method for measurement of PFC tissue concentrations.

PMID- 1391533
TI  - The use of Imagent BP in diagnostic imaging research and 19F magnetic resonance
      for PO2 measurements.
AB  - Imagent BP (90% w/v perflubron emulsion) is radiopaque and serves as an X-ray
      contrast medium. Quantitative X-ray Computed Tomography, provides the means to
      non-invasively estimate tissue perflubron concentration providing three unique
      capabilities: 1) The use of the same animal for biodistribution and elimination
      analysis; 2) The precise geographic distribution of the agent to more accurately
      quantitate localized accumulations; and 3) The ability to gather physiologic data
      by monitoring the time dependent distribution of perflubron. It is known that the
      T1(-1) of 19F of perfluorochemicals is linearly related to the dissolved oxygen
      which allows the quantitation of PO2 in-vivo. We showed using perflubron in
      phanta that not only was T1(-1) linearly related to PO2 but also T2(-1) and both
      were insensitive to perflubron concentration. Since flow interferes with signal,
      the first in-vivo experiments have focused on stationary perflubron located
      within phagocytes. T1(-1) measured from this environment suggested a PO2 of 15-25
      Torr. T1(-1) increased by nearly 50% when the FIO2 was increased from 20 to 100%
      reflecting an increase in intracellular PO2 on the order of 25 Torr.

PMID- 1391535
TI  - Protective effects of a novel perfluorochemical emulsion in photodynamic therapy.
AB  - The effects of pre-injection of mice with a novel perfluorodecalin-based emulsion
      on the responses to photodynamic therapy (PDT) using the photosensitizer,
      metatetra (hydroxyphenyl) porphyrin (m-THPP), have been studied. Injection of
      emulsion after m-THPP and before illumination (activating wavelength 648 nm)
      protected skin against PDT-induced inflammatory effects, as reflected by
      decreases (P less than 0.05) in vascular permeability and oedema formation.
      However, there was no protection against epidermal cell loss. In contrast,
      injection of emulsion before sensitizer had no corresponding effect. A fall in
      mean dermal temperature of up to 6 degrees C occurred in mice injected with
      emulsion 1-2.5 h before illumination suggesting a decrease in skin blood flow
      which would reduce oedema formation. Possible mechanism(s) for this apparent
      protective effect are discussed.

PMID- 1391536
TI  - Oxygent: a novel probe of tissue oxygen tension.
AB  - We have examined the 19F NMR spectrum and relaxation behavior of Oxygent (an
      emulsion of perfluorooctylbromide). Each of the resonances exhibits a linear
      relationship between spin-lattice relaxation rate and oxygen tension at constant
      temperature. Oxygent provides enhanced sensitivity to changes in oxygen tension
      compared with other emulsions used previously. We have used Oxygent to determine
      the oxygen tension in the liver of a mouse.

PMID- 1391537
TI  - A comparison study of rat pancreas preservation using perfluorochemical and
      fluorocarbon-emulsion as preservation medium.
AB  - We reported previously the successful 72-hour cold rat pancreas preservation by
      using Perfluorochemical (PFC). The present study is to determine whether
      Fluorocarbon (FC) emulsion is as effective as PFC for long-term rat pancreas
      preservation. Lewis rat pancreases were stored in FC emulsion (4 degrees C)
      saturated by continuous supply of oxygen:carbon dioxide (95%:5%) (Group I) or by
      100% pure nitrogen (Group II), or in PFC (4 degrees C) saturated by continuous
      supply of oxygen:carbon dioxide (95%:5%) (Group III) or nitrogen (Group IV) for
      24 h and 48 h. Heterotopic pancreas transplantation into isogeneic diabetic rats
      were performed following preservation. Functional graft success rates following
      24 h and 48 h cold storage were 71% (5/7) and 0% (0/5) in Group I, 71% (5/7) and
      0% (0/5) in Group II, 100% (5/5) and 80% (4/5) in Group III, and 80% (4/5) and 0%
      (0/5) in Group IV, respectively. These results showed that, as an artificial
      blood substitute, the PFC with simple oxygen bubbling for 48-hour preservation of
      rat pancreas was much effective than FC emulsion, but not effective when
      saturated with nitrogen. We concluded that the PFC with saturated oxygen can
      obtain long-term successful preservation of rat pancreas. The direct oxygenation
      of the graft tissues is thought to play an important role in organ preservation.

PMID- 1391538
TI  - Extended use of Fluosol emulsion in acute myocardial ischemia treatment.
AB  - An intravenous infusion of Fluosol enhanced significantly the t-PA thrombolysis
      of the arterio-venous shunt made by insertion of 125I-fibrin clot in rabbits. The
      plasma radioactivity released through thrombolysis increased in both time and
      dose-dependent manner after the administration of t-PA. Fluosol in combination
      with t-PA increased the plasma radioactivity, compared with the t-PA treatment
      alone at the corresponding dosage. The coronary blood flow was markedly reduced
      to almost zero after the thrombin injection into narrowed LCX with a clamp in
      open-chest dogs. An intravenous infusion of Fluosol or Pluronic F-68 solution at
      a dose of 15 ml/kg significantly shortened the thrombolysis time by intracoronary
      infusion of urokinase alone. While, little change in the QTc interval of ECG and
      the plasma CPK-MB activity was observed in the Fluosol group in combination with
      urokinase, suggesting a myocardial protective action of Fluosol possibly due to
      its oxygen carrying effect.

PMID- 1391539
TI  - Combination of treatment with perfluorochemicals and free radical scavengers.
AB  - P-cyclohexylmorpholine, given as oxygen carrier of second generation, was tested
      in two experimental models: the ischemic intestine and the lung under hyperbaric
      oxygen condition. In both instances in separated groups either alpha-tocopherol
      or allopurinol was additionally given as oxygen free radical scavenger. The
      thiobarbituric acid reaction (TBAR) was used as screening test for the occurrence
      of lipid peroxidation in organ probes; further the content of glutathione in
      reduced (GSH) and oxidized form (GSSG) was determined. Whereas only slight
      increases of TBAR substances and GSSG could be found compared to controls, the
      effect of the administrated scavenging drugs was very impressive: they could
      suppress nearly totally the effect of an enhanced oxidative stress.

PMID- 1391540
TI  - Effect of Oxygent (perflubron emulsion) on leukocyte-endothelial interaction in
      postcapillary venules.

PMID- 1391541
TI  - Comparison of the effects of total blood substitution during two different levels
      of hypothermic cardiac arrest.
AB  - The effect of total blood replacement with a solution containing neither
      hemoglobin nor fluorocarbon was studied under two different levels of
      hypothermia. Ten dogs were anesthetized and esophageal temperature lowered to
      about 24 degrees at which time exsanguination began. Upon cardiac arrest and the
      completion of exsanguination, continuous whole body closed chest extracorporeal
      circulation of an oxygenated blood substitute was begun. Hematocrit was 1% while
      core temperature remained less than 10 degrees C for 3 hours of perfusion during
      which nadirs of 1.3 degrees C (Group I, N = 5) and 7.3 degrees (Group II, N = 5)
      were achieved. Replacement of the perfusate with whole blood began once the dog
      was rewarmed to approximately 10 degrees C. All dogs survived the procedure. Two
      dogs from each group died by the fourth post-operative day but the others
      survived long term. Group II showed a faster return to normal based on motor
      behavioral, biochemical and hematological changes. Thus the combination of
      profound hypothermia and complete blood substitution with a solution lacking any
      special oxygen carrying molecule, can be tolerated for 3 hours using both levels
      of hypothermia, however, the warmer one appears to be associated with faster
      recovery.

PMID- 1391542
TI  - Preservation of myocardial function during ischemia with intracoronary
      perfluoroocytlbromide (Oxygent).
AB  - The effects of intracoronary infusion (24 ml/min) of oxygenated
      perfluoroocytlbromide (PFOB) or autologous blood on regional myocardial function
      and hemodynamics were studied during a 2 min perfused occlusion in nine open
      chest dogs to determine if a PFOB infusion could prevent the myocardial
      dysfunction observed during the balloon occlusion of percutaneous transluminal
      coronary angioplasty (PTCA). Regional myocardial function was measured with
      sonomicrometers in the ischemic and non-ischemic zone to determine segment length
      and percent of systolic shortening (% delta L). Without infusion, the ischemic
      zone in each animal developed akinesis during a 20 sec coronary occlusion. Each
      animal underwent a 2 min infusion of blood and PFOB at 24 ml/min. During the 2
      min perfused occlusion, the blood ischemic zone % delta L of 14.4 +/- 3.1 versus
      a PFOB % delta L of 23.4 +/- 2.9. % delta L of blood and PFOB were not as
      significantly different from control (P less than .05 PFOB vs. blood). The
      bromine ion in PFOB results in a radiodense compound. Adequate images of the
      canine left ventricle and coronaries were obtained using DSA. CONCLUSION: (1)
      PFOB infusion maintains normal myocardial function during perfused coronary
      inclusion. (2) PFOB may be used as an oxygen carrying contrast agent to obtain
      DSA images.

PMID- 1391543
TI  - Perfluorochemical reperfusion limits myocardial reperfusion injury after
      prolonged hypothermic global ischemia.
AB  - The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial
      reperfusion injury following global hypothermic ischemic insult was investigated.
      Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and
      stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an
      isolated, blood-perfused, working heart preparation. Hearts were initially
      reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified
      perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical
      cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion,
      functional evaluation and left ventricular biopsy. A control group (C, n = 7) was
      evaluated without an intervening period of ischemia. At a left ventricular
      diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work
      index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean).
      Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x
      10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+
      hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less
      than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)).
      In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than
      0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while
      preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased
      over that of PFC (p less than 0.001), and not significantly different from that
      for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391544
TI  - Biocompatibility studies with perfluorochemical oxygen carriers.
AB  - The effects of injecting either a novel perfluorodecalin (FDC)-based emulsion or
      various perfluorochemical (PFC) oils on liver cytochromes P-450 (P-450) and aryl
      esterase (LAE) enzymes in male rats have been studied. Mean P-450 concentration
      increased (P less than 0.05) following injection of the novel emulsion or FDC. In
      contrast, LAE increased in response to injection of FDC (P less than 0.05) and
      the C-16 oil, perfluoroperhydrofluoranthrene (P less than 0.01), added to
      stabilize the emulsion. No corresponding changes in either P-450 or LAE occurred
      in rats injected with either perfluorotripropylamine, perfluorotributylamine or
      perfluorooctylbromide. The "sleeping time" of animals injected with the
      pentobarbital-based anaesthetic, Equithesin, following pretreatment with the
      novel emulsion was lower (P less than 0.05) than in saline-injected controls. The
      results are discussed in relation to the effects of PFCs on liver metabolic
      functions.

PMID- 1391546
TI  - [Uncertainty--suffering and chance].

PMID- 1391545
TI  - [The meaning of suffering. Patients describe their experiences].

PMID- 1391547
TI  - ["Much pain" or the "Mamma mia syndrome". Considerations on the cultural conflict
      in the clinical care of foreign patients].

PMID- 1391548
TI  - [Ethics and research].

PMID- 1391549
TI  - [At home. A varied reality for elderly women and their nursing personnel in
      nursing homes].

PMID- 1391550
TI  - [Implicit strategies for the professionalization of concepts of qualification for
      teachers in the nursing professions].

PMID- 1391551
TI  - [Patient classification and work load in nursing: the SEP-USZ model] (SEP =
      system for the determination of nursing load). (USZ = Zuric University)].

PMID- 1391552
TI  - [Nursing knowledge according to Dorothea Orem's self-nursing model, Part 2.
      Practical use--education--research].

PMID- 1391553
TI  - Structural determinants of vascular resistance properties in hypertension.
      Haemodynamic and model analysis.
AB  - The average internal radius (ri) of the resistance vessels of the hindquarter
      (HQ) bed was narrower in renovascular and genetic hypertension than in
      normotensive controls. The narrowing was approximately uniform over the full
      range of vasomotor tone, which accounted for the bed's property as an 'amplifier'
      of vascular resistance (R) (increased slope (S) of the dose-R response curve) and
      for the elevated R at maximum dilatation (Rmin). In the model we examined the
      effects on the dose-R curve parameters of altering wall/internal radius (w/ri)
      ratio, ri and wall 'stiffness' one at a time, whilst the others were held
      constant: only narrowing of ri led to increases in both S and Rmin; with
      hypertrophy alone, S increased but Rmin was reduced, whilst increased wall
      stiffness increased Rmin but lowered S. Thus, for hypertrophy to be associated
      with rises of both S and Rmin, it must be linked to lumen narrowing, to increased
      wall stiffness, or to both. Preferential deposition of new material towards the
      lumen will link hypertrophy to narrowing. It has been suggested that narrowing
      can occur without hypertrophy ('remodelling'). In the model an increase of only 1
      2% WV was required to produce rises in w/ri of congruent to 30-50% when
      associated with congruent to 10-15% reduction in ri, which is close to the limit
      of detection. From the literature, the sites of greater narrowing in hypertension
      extend down to small arteries and large arterioles. The rise in BP upstream from
      those sites, due to the vascular amplifier, offsets the down-stream effects of
      vascular narrowing on blood flow and this negative feedback system helps to
      maintain elevation of BP at a stable level. We also examined developmental rise
      in R between 4 and 50 weeks, which affected SHR and WKY in the same proportion:
      structural factors (vascular length of larger arteries, 'rarefaction' of
      arterioles and capillaries) accounted for only about half the rise in R, and the
      remainder was probably due to developmental changes in muscle function.

PMID- 1391554
TI  - Alteration of arteriolar responses to serotonin by two intravenous anesthetics.
AB  - The effects of serotonin (5-HT) on the microvasculature of cremaster muscles were
      compared in decerebrate, ketamine- and pentobarbital-anesthetized rats. 5-HT
      induced constriction of large distributing arterioles was enhanced in the
      ketamine- and pentobarbital-anesthetized rats. Precapillary arterioles of
      pentobarbital-anesthetized animals were more sensitive to 5-HT-induced dilation
      than either decerebrate or ketamine-anesthetized animals. The response of vessels
      to two 5-HT receptor antagonists (methysergide and LY53857) were unchanged by the
      anesthetics. Our findings suggest that both ketamine and pentobarbital enhance
      the microvascular response to 5-HT, but that these changes are not due to an
      alteration of receptor sensitivity.

PMID- 1391556
TI  - [Pneumonitis from hypersensitivity: a field for further research].

PMID- 1391555
TI  - Access of blood-borne vasoconstrictors to the arteriolar smooth muscle.
AB  - In vitro experiments have shown that luminally applied water-soluble vasoactive
      materials have limited access to arteriolar smooth muscle cells, and as a result,
      the responses to such agents applied luminally are less than the responses to
      those applied adventitially. To determine the extent to which this
      'compartmentation' influences arteriolar responsiveness to blood-borne water
      soluble vasoconstrictors in vivo, we applied phenylephrine, vasopressin and
      angiotension II to arterioles in the hamster cheek pouch both by luminal
      perfusion, and by topical application to the arteriolar smooth muscle via
      micropipettes. The arterioles were about 2 orders of magnitude more sensitive to
      these water-soluble vasoconstrictors when they were applied topically than when
      they were applied luminally. In contrast, the arterioles were almost equally
      sensitive to the lipid-soluble alpha 1-adrenoceptor agonist SKF 89748-A applied
      by either route. The venular wall appears to be much less effective as a barrier
      than the arteriolar endothelium. Phenylephrine and vasopressin both elicited
      large arteriolar constrictions when perfused through venules in close proximity
      to the arteriole, and these constrictions were larger than those observed when
      the drug was applied to the arteriole's own lumen. Our observations confirm that
      the arteriolar endothelium can inhibit the direct access of water-soluble blood
      borne agents to the arteriolar smooth muscle in vivo, and they suggest that the
      capillaries and venules could be the primary routes of access for water-soluble
      agents from the blood to the arteriolar smooth muscle.

PMID- 1391557
TI  - [Febrile syndrome in hospitalized patients].
AB  - This study was designed to ascertain if certain characteristics of febrile
      patients could help to identify infectious or bacteremic conditions. Patients
      with axillary temperature higher than 37,4 degrees C visiting the emergency room
      and requiring hospitalization were included in the study. The sample included 345
      patients. Infections made up 89% of the causes of fever. The most frequent site
      of infection was the respiratory system (39%). 13% of hemocultures were positive.
      Gram negative germs were the most frequent agents. Infectious FS was related with
      the presence of predisposing factors, duration of fever, erythrocyte
      sedimentation rate and hemoglobin. Bacteremia was associated to treatment prior
      hospitalization, average temperature, hemoglobin, AST and urinary sediment. We
      may conclude that infections are the most frequent cause of FS. We could not
      found any clinical or analytical parameters that, used together, could help us to
      identify infectious or bacteremic FS.

PMID- 1391558
TI  - [Cases of tetanus in Guipuzcoa].
AB  - In order to evaluate the situation of tetanus in Guipuzcoa and to assess the
      impact of preventive measures, we studied the incidence, mortality and other
      aspects of the disease during the past three decades. Ninety eight cases were
      detected (annual average 3,27 SD 2,6), this figure being reduced over time (7,2
      cases per year during the period 1962-1966; 1,8 cases per year between 1987 and
      1991). 67,3% were men and 32,7% women. We registered 6 cases of neonatal tetanus,
      all of them prior to 1976. Since 1969, there has been no cases within the 1-14
      age group. Half of the cases detected during the last five years (4/9) were
      intravenously drug-addicts. Among those living in less populated areas (less than
      10.000 population), the risk of developing the disease was four times greater.
      33,7% of patients died, being the mortality rate higher among newborns and
      patients died, and patients over 55. Although the situation was not worse than in
      other similar environments, the incidence of tetanus should be reduced by
      reinforcing preventive measures.

PMID- 1391559
TI  - [Antibiotic treatment for acute episodes of chronic obstructive pulmonary
      disease].
AB  - Antibiotic therapy for acute episodes of chronic obstructive pulmonary disease
      (COPD) is a controversial issue still not clarified. In order to evaluate the
      effectivity of the antibiotic therapy, we designed a double-blind controlled and
      randomized clinical trial, in which 90 patients hospitalized due to an acute
      episode of COPD were divided into three groups: group I, cotrimoxazole (29
      patients); group II, amoxicillin-clavulanic acid (32 patients) and group III,
      placebo (29 patients). Gasometric and spirometric measures were taken in addition
      to clinical evaluation at hospital admission and discharge using a numerical
      valoration system. All patients were treated with common bronchodilators. The
      three groups were homogeneous at their admission and there were no statistical
      differences at their discharge. We conclude that antibiotics do not play a
      relevant role in the improvement of acute episodes of COPD.

PMID- 1391560
TI  - [Epidemiological study of acute poisoning within the population of Zaragoza].
AB  - Were chosen for analysis 1443 acute poisonings, that were treated in the
      Emergency Services of the Miguel Servet Hospital and the University Hospital of
      Zaragoza between the years 1988 and 89. The great part of the patients didn't
      required hospitable ingress, it was observed a predominance of the voluntary
      poisonings with predominance in people under 40 years. Among the drug poisonings
      were the benzodiazepines the drug more used and among nonpharmacologic agent,
      alcohol and the narcotics. The treatment more used was the symptomatic (53%) and
      was contrast the decrease of gastric lavage (15%) and forced diuresis (10%).

PMID- 1391561
TI  - [Mediastinal tuberculosis as a cause of fever of unknown origin].
AB  - Tuberculosis is the most frequent cause of fever from unknown etiology. On the
      other hand, mediastinal tuberculous adenopathy (TBM), without associated
      pulmonary affection is a rare form of presentation among adults, generally
      evolving with sustained fever until a thoracic radiology is performed showing
      mediastinal enlargement. We present a case which started as fever from unknown
      etiology (FUE), given that, according to the thoracic radiology performed one
      month after the onset of fever, no mediastinal affection was observed.

PMID- 1391562
TI  - [Comments with respect to 2 patients with anti-Jo 1 antibodies].
AB  - Anti-Jo 1 antibodies define a subgroup of patients with polymyositis, which are
      characterized by the presence of extra-muscular involvement as pulmonary
      fibrosis, although Raynaud's phenomena, arthritis, tenosynovitis, pleuritis and
      pericarditis may also be present. Given the fact that extra-muscular signs may
      precede the clinical diagnosis of polymyositis, as in the two cases that we
      present here, these antibodies may help us to diagnose the disease before the
      onset of myositis.

PMID- 1391563
TI  - [Hypothyroidism state with psychomotor agitation and fast atrial fibrillation: a
      rare form of presentation].
AB  - Schizoid psychosis and atrial fibrillation are two rare signs of hypothyroidism
      which may suggest the opposite condition, hyperthyroidism, with the associated
      risk of adopting a wrong therapeutical approach. Recently, we have treated a
      patient in which those two mentioned circumstances were present. In this paper,
      we review psychiatric signs and electrocardiographic disorders associated to
      hypothyroidism.

PMID- 1391565
TI  - [Algodystrophy: predisposing and precipitating factors].

PMID- 1391564
TI  - [Lymphoproliferative syndromes associated with rheumatoid arthritis].
AB  - Rheumatoid arthritis predispose to several lymphoproliferative syndromes, some of
      them are of doubtful neoplastic type, as the lymphoproliferative disease of
      granular lymphocytes, whereas others are clearly malignant, as non-Hodgkin's
      lymphomas and multiple myeloma. In this paper, we review the potential
      etiological agents, mainly the reduction of the "natural killer" activity and
      immunity disorders against virical oncogenes. The onset of monoclonal gammopathy
      in rheumatoid patients is also stressed, due to its potential prognosis value in
      the development of lymphoid neoplasias.

PMID- 1391566
TI  - [Hyperbaric oxygen therapy].

PMID- 1391567
TI  - [Hepatopathy from cyanamide. Presentation of a new case].

PMID- 1391568
TI  - [Ofloxacin in the treatment of lower respiratory tract infections in patients
      with chronic pulmonary diseases].

PMID- 1391569
TI  - [Urinoma].

PMID- 1391570
TI  - [Cardio-compressive recurrent paralysis].

PMID- 1391572
TI  - [Ehlers-Danlos's syndrome and recurrent hemorrhages].

PMID- 1391571
TI  - [Febrile coma with polynucleosis from atropine intoxication].

PMID- 1391573
TI  - [Carotenodermia].

PMID- 1391574
TI  - [Internists and the quality of clinical research].

PMID- 1391575
TI  - [Infections in the diabetic. Comparative study of infections in the foot and
      other locations].
AB  - Given the high morbi-mortality of foot infections among the diabetics and the
      poor knowledge of their predictive, clinical and evolutive factors, we have
      retrospectively studied a group of patients with these characteristics, comparing
      them with infections among diabetics affecting other locations. We studied 66
      infections among diabetics: 34 patients with diabetic's foot and 32 with
      infections at other locations: 20 pyelonephritis and 12 pneumonias. Medical
      records were obtained in all cases and all patients underwent a complete physical
      exploration in order to assess their risk factors. We observed as a significant
      predictive factor of diabetic's foot, diabetes type I, with an evolution longer
      than 10 years, neuropathy, vasculopathy or retinopathy. From the clinical point
      of view and compared with the other infections, these patients showed longer
      hospitalization, greater initial clinical severity, glucemias higher than 200
      mgr/l., anemia and high GSR. Ethiologically, the infection of diabetic's foot was
      polymicrobian in 42.3% of all cases, being S. aureus the microorganism more
      frequently isolated. On the contrary, in infections at other locations,
      monomicrobian flora was more frequent, being E. coli the most frequent in
      pyelonephritis and S. pneumoniae in pneumonias. The evolution was satisfactory in
      all cases, with a close medical and surgical combined treatment and the
      appropriate use of antibiotic combinations, mainly clindamicine + tobramicine in
      the diabetic's foot and cefuroxime in the other locations.

PMID- 1391576
TI  - [Meningitis from Listeria monocytogenes in the adult].
AB  - We describe the characteristics of 6 adult patients with meningitis by Listeria
      monocytogenes. Five of them had previous disease and only one of these was being
      treated with immunosuppressors. All of them presented meningeal syndrome with
      cephalorhachidean fluid's pleocytosis and five of them, polymorphonuclear
      predominance. The empirical treatment was correct only in two cases. The
      mortality rate reached 50%.

PMID- 1391577
TI  - [Seroprevalence of Q fever among the adult population of Lanzarote (Canary
      Islands)].
AB  - Q fever is an endemic zoonosis in the Canary Islands. In 1986, we detected, in a
      pilot study, residual antibodies of the infection in 3% of the population from
      Lanzarote. In 1989, we performed a new study in order to assess seroprevalence of
      Q fever among the adult native population from the island. We studied 390 human
      serums obtained from an statistically representative sample. Age ranged from 30
      to 64 years. Out of 390 serums, 196 (50.25%) were obtained from men and 194
      (49.74%) from women. The serological technique used was the fixation of
      complement using Coxiella burnetii antigens in phase II. Titres equal or higher
      than 1/8 were considered positive. No statistically significant differences were
      observed with regard to seroprevalence rates considering sex, age, nor living in
      or outside the island's capital city. However, when dividing the island's
      territory in three areas (north, centre and south), and assessing independently
      their respective seroprevalences, we observed relatively higher seroprevalences
      in the furthest areas (13.3% in the north and 13.5% in the south) than in the
      central area (4.7%), although only the higher seroprevalence in the south reached
      statistical significance when compared with the mean prevalence. Probably, these
      observations indicate that, although Q fever is extended all over the island, it
      is a more frequent infection in rural areas of Lanzarote, at the north and the
      south, than in the central area, where the main urban areas are located.

PMID- 1391578
TI  - [Study of smoking habit among the adult population of Aragon].
AB  - We determined the prevalence of tobacco consumption among the general population
      and established its distribution considering socioeconomical variables. We
      performed a cross-sectional study with 2781 subjects from 93 rural and urban
      areas, selected by randomized, census-based, multi-staged and stratified
      sampling. 40.9% of the population from Aragon are regular smokers (58.6 of men
      and 23% of women). Heavy smokers comprise 17.2% of the total (30.1% of men and
      3.8% of women). The higher proportion of smokers in observed among single men
      over 40 and single women under 40. The percentage of smokers is lower among 20 to
      29-years-old young people from high socio-economical than from low levels. In
      general, the mean percentage of smokers among men and, specially, among women
      from rural areas is higher than in the rural areas. In Aragon, tobacco is a risk
      factor affecting 41% of the adult population and, specially, young people, men,
      single persons from both sexes and living in urban areas. It seems that young
      people with a high socio-economical level are becoming smokers at a lower
      frequency.

PMID- 1391579
TI  - [Prolonged febrile syndrome as a manifestation of Coxiella burnetii infection,
      presentation of infrequent clinical cases].
AB  - We present two cases of infection by Coxiella burnetii which developed with
      sustained fever symptoms. During its evolution, the first case presented
      granulomatous hepatitis, whereas the second case presented left Cosofemoral
      Arthritis. We describe the clinical-evolutive characteristics of these clinical
      forms and within the evolution of the chronic forms of Q fever.

PMID- 1391580
TI  - [Cerebellar syndrome as first manifestation of late onset systemic lupus
      erythematosus].
AB  - Clinical characteristics of a 70-year-old women affected by an erythematous
      systemic lupus (ESL) of late onset, whose first main manifestation was the
      compromise of the central nervous system as cerebellar syndrome and which
      exhibited a good response to treatment, is described. Pathogenic and diagnostic
      aspects of the neurological manifestations of ESL are described.

PMID- 1391581
TI  - [Pre-sternal invasion as first manifestation of lung epidermoid carcinoma].
AB  - Lung epidermoid carcinoma is a tumor of central origin and slow growth which
      tends to invade locally; however, it is rare to find a presternal tumoration
      produced by local invasion as one of its manifestations. The aim of this
      communication is to present a case and analyze its natural history.

PMID- 1391583
TI  - [Omeprazole and maintenance treatment: new concepts for traditional therapies?].
AB  - Duodenal ulcer and reflux oesophagitis are a chronic diseases characterized by
      remission and relapses. If no active prophylactic treatment is given after
      healing around 70-100% of the patients have a relapse during the first year.
      Various therapeutic strategies have been suggested to maintain the disease in
      remission. Continuous maintenance treatment with H2 blockers has proved to be
      effective in reducing the spontaneous recurrence rate of duodenal ulcers but the
      results are disappointing in reflux oesophagitis. Initials studies on different
      treatment regimen of omeprazole for maintenance treatment have indicated
      promising results. The efficacy and safety of this drug have been evaluated in
      this article.

PMID- 1391582
TI  - [Pheochromocytoma: a motley tumor].
AB  - Four patients admitted to our hospital with different symptomatology are studied:
      a 9-years-old boy with hyperhidrosis; a 47-years-old woman with arterial
      hypertension and two young males, 25 and 36-years-old, respectively, with
      thoracic pain. In all cases, the presence of pheochromocytoma was suspected. One
      of them died due to left ventricular failure with acute lung edema. The other
      three patients were diagnosed by hormonal determinations, detecting a supra-renal
      body with abdominal echography and computerized axial tomography and undergoing
      surgery. Currently, they are asymptomatic.

PMID- 1391585
TI  - [Diffuse cutaneous infiltration as a presenting form of acute monocytic
      leukemia].

PMID- 1391584
TI  - [Clinical syndromes in HIV infection (1st of 2 parts)].
AB  - The spectrum of clinical manifestations associated to HIV infection is very
      broad. In addition to processes that may be attributed to the virus itself,
      multiple opportunistic infections can develop while the immunodeficiency
      develops. Any organ or system of the organism may be affected by these processes.
      The main clinical syndromes in AIDS and the differential diagnosis of their
      potential etiologies are reviewed.

PMID- 1391586
TI  - [Side effects of aerosolized pentamidine in the prophylaxis of pneumocystis
      pneumonia].

PMID- 1391588
TI  - [Active chronic hepatitis associated with lichen planus].

PMID- 1391587
TI  - [Increase of ceruloplasmin levels in patients with chronic obstructive pulmonary
      disease].

PMID- 1391590
TI  - [Vertebral pedicle hypoplasia associated with sciatic syndrome].

PMID- 1391589
TI  - [Primary amyloidosis with diffuse retroperitoneal disease detected by
      computerized axial tomography].

PMID- 1391592
TI  - [Brucellar pericarditis].

PMID- 1391591
TI  - [Hodgkins disease. Criteria for AIDS?].

PMID- 1391593
TI  - International conference on cellular and molecular aspects of self-reactivity and
      autoimmune disorders. Taormina, Italy, June 7-12, 1992. Abstracts.

PMID- 1391594
TI  - Spectrotypes of anti-DNA antibodies show that anti-DNA-secreting B-cell clones of
      SLE patients are restricted in number, stable and long lived.
AB  - We have investigated the number of B-lymphocyte clones secreting anti-ssDNA
      antibodies in SLE patients and a chronic active hepatitis patient by isoelectric
      focusing and reverse immunoblotting of serum antibodies. Individual clones can be
      identified by the unique pattern of bands produced by their antibodies (the
      clonotype). Using this technique, we have shown that the anti-DNA response of the
      majority of SLE patients is clonally restricted, in many cases only a single B
      cell clone responding. We have also measured qualitative and quantitative changes
      in expression of B-cell clones and shown that these clones are remarkably stable
      with lifespans of up to six years or more. These results are in agreement with
      previous observations of clonal restriction of the anti-DNA response in three
      mouse models of SLE and in addition show that, unlike the mouse models, human
      anti-DNA-secreting B-cell clones are extremely stable and long-lived. The
      implications of these results for models of initiation and regulation of the
      autoimmune response are discussed.

PMID- 1391595
TI  - Analysis of carbohydrate residues on human thyroid peroxidase (TPO) and
      thyroglobulin (Tg) and effects of deglycosylation, reduction and unfolding on
      autoantibody binding.
AB  - The contribution of carbohydrate residues and peptide chain conformation to
      autoantibody binding sites on human thyroid peroxidase (TPO) and thyroglobulin
      (Tg) has been investigated. In addition the nature of carbohydrate residues
      associated with human TPO has been studied. 125I-labelled human TPO and Tg were
      treated with the following glycosidases: EndoD, EndoH, neuraminidase, O
      glycanase, neuraminidase followed by O-glycanase and PNGaseF. Thereafter binding
      to different sera containing TPO autoantibodies and Tg autoantibodies was
      assessed using solid phase protein A to separate antibody-bound and free labelled
      antigens. In addition, labelled Tg and TPO were treated with reducing agent
      (dithiothreitol) or sodium acetate buffer pH 7.5, 5.5 and 3.2 (followed by
      neutralisation with 2 M Tris pH 8.3) prior to antibody binding studies.
      Furthermore, the effect of deglycosylation and treatment with acid buffers on TPO
      enzyme activity was studied. The nature of carbohydrate residues associated with
      hTPO was analysed by assessment of the effects of different glycosidases on 125I
      TPO mobility on SDS-PAGE followed by autoradiography and by the use of lectins.
      Deglycosylation of labelled Tg and TPO had no clear effect on Tg and TPO
      autoantibody binding. Reduction of labelled Tg and TPO resulted in almost
      complete loss of autoantibody binding with all sera studied. Furthermore,
      adjusting the pH of labelled TPO or Tg transiently to pH 5.5 lowered autoantibody
      binding in the case of all the sera and the effect was more marked at pH 3.2. TPO
      enzyme activity (guaiacol assay) of unlabelled TPO was decreased after treatment
      with EndoH but not with other glycosidases. The low pH buffers affected
      unlabelled TPO enzyme activity measured by iodide assay. Treatment of 125I
      labelled TPO with EndoH, neuraminidase and PNGaseF caused marked changes in the
      double band pattern characteristic of TPO on analysis by SDS gel electrophoresis
      (TPO doublet). Analysis of changes in the mobility of the 2 bands of the doublet
      after treatment with different glycosidases and binding studies with lectins
      indicated that both high mannose and complex type sugar residues were associated
      with hTPO. The high mannose type residues were associated mostly with the lower
      band of the hTPO doublet whereas complex type residues were associated mostly
      with the upper band. Overall, our studies indicate that (1) the major
      autoantibody binding sites on hTPO and hTg are conformational, (2) sugar residues
      do not appear to be important in forming the autoantibody binding sites on hTPO
      and hTg, and (3) both high mannose type and complex type sugar residues are
      associated with hTPO.

PMID- 1391596
TI  - Non-receptor muscle antibodies in myasthenia gravis are of IgG1 and IgG4
      subclasses.
AB  - The IgG subclass distribution of non-receptor muscle antibodies was examined in
      15 myasthenia gravis (MG) sera, employing an indirect haemagglutination
      immunofluorescence technique. Four sera contained only IgG1, 4 contained only
      IgG4 and 7 contained both IgG1 and IgG4 muscle antibodies. IgG2 and IgG3
      antibodies were not found. Among 11 patients with a defined thymus pathology 8
      had thymoma and 3 had thymic atrophy, but there was no correlation between
      antibody subclass pattern and thymic pathology. Patients with both IgG1 and IgG4
      antibodies tended to have the longest disease duration. We conclude that IgG non
      receptor muscle antibodies in MG are of the IgG1 and/or IgG4 subclasses,
      irrespective of thymic pathology.

PMID- 1391597
TI  - Target organ susceptibility and autoantibody production in an animal model of
      spontaneous autoimmune thyroiditis.
AB  - F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune
      thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe
      thyroiditis. About 50% of these crosses show circulating autoantibodies to
      thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated,
      suggesting that the target organ is not susceptible to autoimmune attack. In the
      present study we show that despite this mild infiltration TgAAb are only
      synthesized by lymphoid cells within the thyroid gland. Furthermore, we
      demonstrate that immunization with chicken thyroglobulin (Tg) in complete
      Freund's adjuvant causes severe experimental autoimmune thyroiditis (EAT) in
      F1(OSxCB) hybrids.

PMID- 1391598
TI  - Genetic association between natural autoantibody responses to histones and DNA in
      murine lupus.
AB  - Genetic regulation of the spontaneous anti-histone antibody production in
      systemic lupus erythematosus (SLE) was studied using the H-2-congenic and T cell
      receptor beta chain gene complex (TCR beta)-congenic NZB and NZW strains and
      their crosses. We found that the original, parental H-2d/d NZB mice produced
      significantly higher titers of serum IgM class anti-histone antibodies than did
      the congenic H-2d/z or H-2z/z NZB mice. However, none of these three NZB strains
      produced IgG antibodies. The NZW strain of any H-2 haplotype did not produce IgM
      and IgG anti-histone antibodies. The IgG anti-histone antibodies were produced
      only by H-2d/z heterozygous NZB x NZW F1, but not by homozygous H-2z/z or H-2d/d
      NZB x NZW F1 mice. In studies using (NZB x NZW) F1 x NZB backcross mice, only the
      progeny having both H-2d/z and NZW-type TCR beta genotypes produced high amounts
      of IgG antibodies. There was a tight linkage between the NZW-type TCR beta and
      the production of IgG anti-histone antibodies in TCR beta-congenic NZB x NZW F1
      mice. All these findings were in keeping with our preceding observations on the
      genetic regulation of anti-DNA antibodies in these mice and suggest that certain
      common mechanisms such as super-antigen-mediated or common idiotope-mediated
      regulations may underlie the production of these two distinct autoantibodies in
      NZB x NZW F1 mice.

PMID- 1391599
TI  - Presence of anti-acetylcholine receptor antibodies in human milk: possible
      correlation with neonatal myasthenia gravis.

PMID- 1391600
TI  - [Diagnostic possibilities of transcranial magnetic stimulation in diseases of the
      cervical spine].
AB  - We investigated the question as to whether transcranial magnetic stimulation of
      nerve structures can be used to obtain an objective description of motor
      impairment in humans with cervical nerve root compression or myelopathies. We
      were able to show that paresis is correlated with an increase in the latency of
      the evoked muscle potentials. Application of the method in the fields of
      orthopaedics and neurosurgery permits a description of motor deficits in cervical
      compression radiculopathy and myelopathy. Although the value of the method for
      orthopaedic and neurosurgical purposes is not yet completely clear, our
      experience does indicate interesting possibilities in the diagnostic evaluation
      of diseases of the cervical spine.

PMID- 1391601
TI  - [Measuring intracardiac impedance for determining sympathetic nerve activity in
      frequency-adjustment electrostimulation--1: Biomedical technical principles].
AB  - Modern Pacemaker technology makes it possible to adapt the pacing rate to
      hemodynamic requirements. The most ambitious approach aims at restoring the
      physiological closed-loop system by utilizing the information supplied by the
      Autonomic Nervous System and extracted from myocardial contractile performance.
      Measurement is accomplished by the impedance method using the stimulating
      electrode as the measuring electrode. The Ventricular Inotropic Parameter (VIP)
      has been identified as an ANS-dependent parameter. A special detection algorithm,
      the Regional Effective Slope Quantity (RQ), with a high ANS sensitivity has been
      developed specially for the purpose. Rate adaptation is achieved by using an
      individually-adjustable Inotropic Index (II). The concept has been evaluated in a
      multicenter study employing a standardized exercise protocol. The clinical
      results will be presented in Part 2 of this paper.

PMID- 1391602
TI  - [Model for immunologic testing of biomaterials].
AB  - Corrosion products and electric fields are capable of changing proteins to
      antigens, thus permitting the immunological system to identify the biomaterial as
      foreign. The reaction between corrosion products and a macro-molecule also leads
      to an antigen (carrier antigen), such as conformational changes of a macro
      molecule, e.g. a protein, caused by the electric field at the implant surface
      (modified macro-molecule antigen). While the sensitivity to corrosion and the
      effectiveness of galvanic elements is measurable by electrochemical methods,
      suitable methods of determining the field strength in the vicinity of biomaterial
      surfaces are still unavailable. The influence of the double layer of uncoated and
      coated titanium surfaces on the conformation of proteins and their conversion to
      antigens are investigated with polyclonal antibodies capable of identifying the
      unchanged protein despite adsorption to the surface. 14C-marked Bovine Serum
      Albumin serves as a model protein. Determination of the total number of protein
      molecules adsorbed is effected via the detection of the emitted electrons. The
      quotient of the concentration of natural proteins to the concentration of
      adsorbed molecules gives the biocompatibility index, which is independent of the
      surface area, and gives an indication of the expected biocompatibility of the
      material. The results of the biological tests of titanium and two coating
      materials on titanium were confirmed in an animal experiment. It is possible that
      in the future immunological tests may replace experiments in animals.

PMID- 1391603
TI  - [Possibilities of myoelectric control of artificial limb prostheses].
AB  - This article summarizes the main possibilities for myoelectrical control of
      prostheses and other rehabilitation devices. In this context fundamental
      cybernetic aspects, the question of achieving optimal differentiation of
      antagonistic signals, and 16 possibilities of myoelectrical control, ranging from
      simple n-state threshold detectors to rate sensitive controllers, to intelligent
      controllers and pattern recognition techniques, are considered.

PMID- 1391604
TI  - [Determination of the heart minute volume by computer-assisted evaluation of
      pulse waves in the rabbit model--short report].

PMID- 1391605
TI  - [Measuring intracardiac impedance for the determination of sympathetic nerve
      activity in frequency-adapted electrostimulation--Part 2: Clinical results].
AB  - The results of a multicenter clinical study involving patients receiving the
      first ANS controlled rate adaptive pacemaker are presented. In the patients with
      primary or secondary chronotropic insufficiency, it is possible to reestablish
      the closed loop control system that includes the baroreceptors, the medulla
      oblongata, the cardiac output and the mean arterial blood pressure. This system
      serves to keep the blood pressure constant in the face of changing demands on the
      circulation. Utilizing intracardiac impedance measurements, the myocardial
      contractility can be determined, which contains information about the current
      sympathetic tone, and thus represents an excellent physiological input for a rate
      adaptive mechanism. The results presented are taken from a study population of
      over 200 patients. The objective evaluation of this new approach was performed
      echocardiographically, by ergometry and 24-hour Holter monitoring.

PMID- 1391606
TI  - [Reduction of the number of recorded EEG channels for routine monitoring in the
      intensive care unit].
AB  - Monitoring patients in the intensive care unit with the aid of the conventional
      electroencephalogram employing a large number of recording channels is rather
      difficult, and can be laborious. This imposes limits on the routine application
      of this method. To investigate the possibility of developing a new monitoring
      device for easier application in the ICU, we aimed to establish whether the
      relevant information provided by a multi-channel EEG could be found in a subgroup
      of channels, thus reducing the number of channels required. Preferably those
      channels should be identified for use which are least contaminated by artefacts
      under routine conditions in the ICU. A total of 150 EEG recordings from the
      intensive care unit were inspected visually for the presence of artefacts. The
      derivations C3-P3 and C4-P4 proved to be least contaminated, at 35% and 39%,
      respectively. In these derivations visual assessment of the EEG was found to be
      impossible due to artefacts in only 4 and 5%, of all cases, respectively. A data
      set comprising 52 EEG segments with the fewest possible artefacts, was analysed
      using time series methods. On the basis of multivariate autoregressive processes,
      a measure was derived which describes the loss of information associated with a
      reduction in the number of EEG channels. The computation of the information loss
      for several channel combinations revealed that the derivations F3-C3, C3-P3 and
      A1-Cz represent a good compromise between information content, number of channels
      and frequency of artefacts. Practical experience shows that, at least for the
      control of sedation, a further reduction to a single channel should be
      possible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391607
TI  - [A comparative study of the characteristics of femoral hip prosthesis heads-
      study and results ceramic-coated hip joint heads of titanium].
AB  - Today, only hard/soft cup and femoral head combinations are employed for hip
      joint prostheses. Highly polished ceramic is a material with very good
      tribological properties for femoral heads, being highly resistant to mechanical
      wear and tear, and highly resistant to chemical reactions in the biological
      environment. The advantage of metal heads, in contrast, undoubtedly lies in their
      resistance to breakage and the ease with which their geometry can be modified
      with respect, for example, to antirotation angle and neck length. The ideal
      material for femoral heads is a combination of the two materials. The new multi
      layer combination of titanium-niobium oxide/nitride ceramic coating applied to a
      prehardened titanium head combines the positive material properties in an ideal
      manner. Femoral heads made of CoCrMo, oxide-hardened titanium, aluminium oxide or
      multilayer titanium-niobium ceramic were compared by means of friction an wear
      and tear tests. The TiNb-ceramic-metal heads showed similar abrasion at the
      surface as the ceramic heads. At the high loads of more than 400 kp, which may
      also be reached under physiological conditions, the specially coated titanium
      ceramic heads proved to be superior in terms of resistance to fracture and
      tribological properties.

PMID- 1391608
TI  - Motions studies of the human alpha 1-acid glycoprotein (orosomucoid) followed by
      red-edge excitation spectra and polarization of 2-p-toluidinylnaphthalene-6
      sulfonate (TNS) and of tryptophan residues.
AB  - Dynamics studies on tryptophan residues of human alpha 1-acid glycoprotein
      (orosomucoid) and of 2-p-toluidinylnaphthalene-6-sulfonate bound to the protein
      are performed. Excitation at the red edge of the absorption spectrum of the
      tryptophan does not lead to a shift of the fluorescence emission maximum of the
      fluorophore. This reveals that Trp residues present motions with respect to their
      microenvironment. This is confirmed by polarization studies as a function of
      temperature. Excitation at the red edge of the absorption spectrum of TNS leads
      to an important shift (15 nm) of the fluorescence emission maximum of the probe.
      This reveals that emission of TNS occurs before relaxation of the amino-acids
      dipole occurs. Emission from a non-relaxed state means that TNS molecules are
      bound tightly to the protein, a result confirmed by polarization studies.

PMID- 1391609
TI  - Fluorescence lifetime distribution of 1,8-anilinonaphthalenesulfonate (ANS) in
      reversed micelles detected by frequency domain fluorometry.
AB  - The fluorescence emission decay of ANS (1,8-anilinonaphthalenesulfonate) in
      reversed AOT (sodium bis-(2-ethyl-1-hexy)sulfosuccinate) micelles at different
      water contents was investigated by frequency domain fluorometry. The whole ANS
      emission decay in reversed AOT micelles could not be fitted in terms of discrete
      lifetime values, i.e., mono-exponential and bi-exponential models. Better fits
      were obtained when using continuous unimodal Lorentzian lifetime distributions.
      This was interpreted as arising from the reorientation processes of water
      molecules around the excited state of ANS or probe exchange among different probe
      locations, occurring on a time scale longer than fluorophore lifetime. The
      dependence of ANS fluorescence anisotropy on the emission wavelength was
      consistent with the existence of a great emission heterogeneity especially for
      inverted micelles having reduced H2O/AOT molar ratio. Finally, the observation
      that the distribution width decreases with increasing temperature and/or micelle
      size suggested that fast processes of water dipolar reorganization around the
      fluorophore are facilitated under these conditions.

PMID- 1391610
TI  - Different superstructural features of the complexes between spermine and the
      light responsive elements of the two pea genes rbcS-3A and rbcS-3.6. Gel
      electrophoresis and circular dichroism studies.
AB  - Two light responsive elements (LREs), DNA sequences, 62 base pairs long, relevant
      to the light control during transcription of the pea genes rbcS-3A and rbcS-3.6,
      were synthesized and ligated to obtain multimers with defined superstructural
      features. Their gel electrophoretic mobilities were studied in the presence of
      the tetracation, spermine, since it was previously suggested, on the basis of
      theoretical analysis, that spermine can increase DNA bending and thus could be
      useful in revealing DNA superstructural features. In fact, the difference between
      the curvatures of the two LREs, derived from gel electrophoresis retardation
      ratios, increases in the presence of spermine. Circular dichroism spectra of the
      complexes between spermine and the two LREs, at different neutralization ratios,
      show that the polyamine is able to induce the formation of asymmetric
      arrangements of complexes of molecules. The chirality of these complexes appears
      dramatically different for the two LREs, suggesting that their different
      superstructural features give rise to different interactions with the polyamine.

PMID- 1391611
TI  - Relevance of urinary DNA adducts as markers of carcinogen exposure.

PMID- 1391612
TI  - Three new microcystins, cyclic heptapeptide hepatotoxins, from Nostoc sp. strain
      152.
AB  - Three new cyclic heptapeptide hepatotoxins, [D-Ser1,ADMAdda5]microcystin-LR (1),
      [D-Asp3,-ADMAdda5]microcystin-LHar (2), and [ADMAdda5,Mser7]microcystin-LR (3),
      were isolated from the cyanobacterium (blue-green alga) Nostoc sp. strain 152,
      together with four known microcystins, [ADMAdda5]microcystin-LR (4),
      [ADMAdda5]microcystin-LHar (5), [D-Asp3,-ADMAdda5]microcystin-LR (6), and
      [DMAdda5]microcystin-LR (7). The structures of new microcystins were assigned on
      the basis of high-resolution fast atom bombardment mass spectrometry (HR FABMS),
      collisionally induced tandem FABMS (FABMS/MS), amino acid analysis, and gas
      chromatography (GC) on a chiral capillary column. All three new toxins contained
      9-acetoxy-3-amino-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (ADMAdda)
      instead of the corresponding 9-methoxyl derivative (Adda), while 7 contains the
      corresponding 9-hydroxy analog (DMAdda). Compound 1 is the first microcystin
      reported that contains D-serine (D-Ser) in lieu of the D-alanine (D-Ala) unit
      which was thought to be an invariable amino acid component of the microcystins.
      Compound 2 has L-homoarginine (Har) instead of L-arginine (L-Arg) in 6 and D
      aspartic acid (D-Asp) instead of D-erythro-beta-methylaspartic acid (D-MeAsp) in
      5. Compound 3, the N-methylserine (Mser) variant of the N-methyldehydroalanine
      unit in 4, would be a biosynthetic precursor of 4.

PMID- 1391613
TI  - Glutathione conjugation of aflatoxin B1 exo- and endo-epoxides by rat and human
      glutathione S-transferases.
AB  - Much evidence supports the view that the rate of conjugation of glutathione (GSH)
      with aflatoxin B1 (AFB1) exo-epoxide is an important factor in determining the
      species variation in risk to aflatoxins and that induction of GSH S-transferases
      can yield a significant protective effect. An assay has been developed in which
      the enzymatic formation of the conjugates of GSH and AFB1 exo-epoxide and the
      recently described AFB1 endo-epoxide is measured directly. 1H NMR spectra are
      reported for both the AFB1 exo- and endo-epoxide-GSH conjugates. Structural
      assignments were made by comparison with AFB1 exo- and endo-epoxide-ethanethiol
      conjugates, for which nuclear Overhauser effects were measured to establish
      relative configurations. The endo-epoxide was found to be a good substrate for
      GSH conjugate formation in rat liver cytosol while mouse liver cytosol conjugated
      the exo-epoxide almost exclusively. Human liver cytosol conjugated both epoxide
      isomers to much lower extents than did cytosols prepared from rats or mice.
      Purified rat GSH S-transferases catalyzed the formation of the AFB1 exo-epoxide
      GSH conjugate in the order 1-1 approximately 4-4 approximately 3-3 greater than 2
      2 greater than 4-6 (7-7 and 8-8 did not form the exo-epoxide-GSH conjugate at
      levels above the nonenzymatic rate). The only rat GSH S-transferases that
      conjugated the endo-epoxide were 4-4 and 4-6, with 4-4 being the more
      active.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391614
TI  - Characterization of DNA adducts formed in vitro by reaction of N-hydroxy-2-amino
      3-methylimidazo[4,5-f]quinoline and N-hydroxy-2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline at the C-8 and N2 atoms of guanine.
AB  - The covalent binding of the carcinogenic N-hydroxy metabolites of 2-amino-3
      methylimidazo-[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) to deoxynucleosides and DNA was investigated in vitro. Two
      major adducts were formed by the reaction of the N-acetoxy derivatives of IQ and
      MeIQx with deoxyguanosine (dG); however, no adducts were formed with
      deoxycytidine, deoxyadenosine, or thymidine. From proton NMR and mass
      spectroscopic characterization the adducts were identified as 5-(deoxyguanosin-N2
      yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-N2-IQ),N-(deoxyguanosin-8-yl)-2
      amino-3-methylimidazo-[4,5-f]q uinoline (dG-C8-IQ), 5-(deoxyguanosin-N2-yl)-2
      amino-3,8-dimethylimidazo[4,5-f]qu inoxaline (dG-N2-MeIQx), and N-(deoxyguanosin
      8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]qui noxaline (dG-C8-MeIQx). The level of
      dG-C8 adducts was approximately 8-10 times greater than the amount of dG-N2
      adducts formed from the reaction of dG with the N-acetoxy derivatives of IQ and
      MeIQx. The C-8-substituted dG adduct was also the major adduct formed from
      reactions of DNA with N-acetoxy-IQ and N-acetoxy-MeIQx. Approximately 60-80% of
      the bound carcinogens were recovered from DNA as dG-C8 adducts upon enzymatic
      digestion. The dG-N2 adducts also were detected and accounted for approximately
      4% of the bound IQ and 10% of the bound MeIQx. These results suggest that the
      relative contributions of the nitrenium and carbenium ion resonance forms as well
      as DNA macromolecular structure are major determinants for DNA adduct
      substitution sites. Investigations on adduct conformation of 1H NMR spectroscopy
      revealed that the anti form is preferred for the dG-N2 adducts of IQ and MeIQx,
      while the syn form is preferred for the dG-C8 adducts. The possible role of these
      adducts in the initiation of carcinogenesis is discussed.

PMID- 1391615
TI  - Characterization of isothiocyanates, thioureas, and other lysine adduction
      products in carbon disulfide-treated peptides and protein.
AB  - Carbon disulfide (CS2) is an industrial solvent used in rayon production and as
      an organic synthetic precursor. It is also a member of the class of neuropathy
      inducing xenobiotics known as the "neurofilament (NF) neurotoxicants". Current
      hypotheses propose direct reaction of CS2 with NF lysine epsilon-amine moieties
      as a step in the mechanism of this neuropathy. In this study, covalent CS2
      binding in a lysine-containing dipeptide and in bovine serum albumin (BSA) in
      vitro was characterized. Dipeptide and BSA, incubated with 14CS2, exhibited
      stable incorporation of radioactivity after removal of unbound CS2 and
      reincubation in physiological buffer for up to 10 days. In contrast, free thiol
      levels decreased from a maximum immediately following CS2 exposure to near-base
      line levels after 10 days, consistent with time-dependent conversion of initially
      formed N-substituted dithiocarbamate adducts into secondary products.
      HPLC/thermospray-MS and HPLC/UV photodiode-array analysis of CS2-dipeptide
      adducts confirmed dithiocarbamate formation and demonstrated their conversion
      into N-alkylisothiocyanates and, ultimately, N,N'-disubstituted thioureas and
      ureas. The results of UV spectrophotometry of CS2-treated BSA were also
      consistent with loss of dithiocarbamate and appearance of thioureas. Similar time
      dependent formation of these products, in addition to N,N'-disubstituted thiuram
      disulfides, was demonstrated in CS2-treated BSA by means of 13C-NMR spectroscopy.
      SDS-PAGE analysis of adducted protein revealed a discrete, higher mobility band,
      likely representing a specific intramolecular cross-link. In contrast, no
      evidence for intermolecular protein cross-linking was obtained. Identical results
      were obtained with cysteinyl-blocked BSA, indicating the lack of formation of N,S
      dialkyldithiocarbamate (dithiourethane) cross-links in these
      preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391616
TI  - Ozonation of methyl oleate in hexane, in a thin film, in SDS micelles, and in
      distearoylphosphatidylcholine liposomes: yields and properties of the Criegee
      ozonide.
AB  - We here explore the use of Criegee ozonides as markers of ozone damage to lipids
      in systems that model pulmonary surfactant, lung lining fluids, and/or pulmonary
      membranes. Ozonation of methyl oleate in hexane gives an 89% yield of the Criegee
      ozonide. The presence of water should reduce the yield of this ozonide, and as
      expected, small but significant yields of Criegee ozonides are formed when the
      ozonation of methyl oleate is carried out as a film over phosphate buffer, in
      aqueous micelles of sodium dodecyl sulfate (SDS), or in distearoyl-L-alpha
      phosphatidylcholine (DSPC) liposomes spiked with methyl oleate. Analysis utilizes
      reversed-phase HPLC and 1H NMR. The total yield of ozonides in 0.02 M SDS
      micelles exposed to 26 ppm ozone for 3 h at pH 7.4 and 22 degrees C is 11%; 7.5%
      is the normal ozonide, methyl 5-octyl-1,2,4-trioxolane-3-octanoate (MOO2) (ca.
      4.2% trans and ca. 3.3% cis), and 3.5% is accounted for by the two cross
      ozonides, 3,5-dioctyl-1,2,4-trioxolane (MOO1) and dimethyl 1,2,4-trioxolane-3,5
      dioctanoate (MOO3). No significant difference of ozonide yields is observed for
      ozonations with 26 ppm and 1.2% (12,000 ppm) ozone. The conversion of methyl
      oleate increaes with increasing SDS concentration. Approximately comparable
      yields of ozonides also are found in the ozonation of methyl oleate in DSPC
      liposomes although yields are not quantified. The ozonides slowly hydrolyze at pH
      7.4 and 37 degrees C with half-lives for trans-MOO2 and cis-MOO2 in 0.10 M SDS
      micelles of 23 and 6 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391617
TI  - A comparative toxicological investigation of perfluorocarboxylic acids in rats by
      fluorine-19 NMR spectroscopy.
AB  - Male Fischer-344 rats administered a single intraperitoneal dose of perfluoro-n
      octanoic acid (PFOA) or perfluoro-n-decanoic acid (PFDA) display a similar
      "wasting toxicity" characteristic of perfluorocarboxylic acids, with marked
      differences in temporal expression. Food/water consumption and urine output were
      monitored daily in PFOA-treated, PFDA-treated, and control rats. Fluorine-19
      nuclear magnetic resonance (NMR) spectroscopy was used to monitor these
      fluorocarbons and possible fluoro metabolites in vivo, and to correlate
      differences in elimination with differences in effective toxicity. The data
      reveal a prolonged hypophagic response to PFDA and a more acute but transient
      response associated with PFOA treatment. PFOA causes a greater decline in food
      consumption than PFDA within the first 24 h postdose. PFOA-treated rats also show
      a ca. 2.5-fold increase in urine output on day 1, with only a slight increase in
      water consumption. In contrast to PFDA, PFOA-treated rats recover from hypophagia
      within 8 days. Fluorine-19 NMR spectra of various bodily fluids and liver in vivo
      display resonances of the parent PFOA or PFDA compounds and do not reveal any
      evidence of metabolism. Inorganic fluoride from dietary sources is detected in
      urine from both exposed and control rats. Differences in the route of excretion
      of PFOA vs PFDA are apparent from the spectral signal-to-noise ratio. The data
      suggest that PFOA is more readily excreted in the urine while PFDA is
      preferentially carried in bile. These apparent differences in elimination may
      account for their observed differences in effective toxicity. The acute transient
      toxicity and higher LD50 associated with PFOA may result from its rapid renal
      clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391618
TI  - Differential effects of thiols on DNA modifications via alkylation and Michael
      addition by alpha-acetoxy-N-nitrosopyrrolidine.
AB  - The hepatocarcinogen NPYR is metabolically activated by alpha-hydroxylation
      mediated by cytochrome P-450 enzymes to yield a 4-oxobutylating agent and 2
      butenal (crotonaldehyde). Both are reactive intermediates capable of modifying
      DNA with guanine either by simple alkylation or by Michael type addition,
      respectively. In order to assess the roles of these pathways in NPYR
      tumorigenesis, we are interested in identifying agents which can selectively
      modify one of these two pathways. In this study, we examined the effects of three
      thiols--(mesna), glutathione (Glu), and N-acetylcysteine (Nac)--on DNA adduct
      formation by alpha-acetoxyNPYR, a stable precursor of alpha-hydroxyNPYR. Calf
      thymus DNA isolated from incubation of alpha-acetoxyNPYR with or without thiol
      was hydrolyzed and analyzed for the adducts formed by alkylation (adducts 1 and
      2) and Michael addition (adducts 3-5). The results showed that the addition of
      mesna completely blocked the formation of the crotonaldehyde-derived adducts 3-5,
      whereas it exerted little effect on the formation of the alkylated adducts 1 and
      2. These results indicate the preferential conjugation of mesna with
      crotonaldehyde. In contrast, Nac had little selectivity on adduct formation;
      levels of adducts 1 to 5 were were reduced by 36-75%. These results suggest that
      Nac conjugated with both alkylating agent and crotonaldehyde. Similar to mesna,
      Glu blocked the formation of the crotonaldehyde-derived adducts (adducts 3-5)
      efficiently. However, unlike mesna, Glu inhibited the formation of adduct 1,
      while it did not inhibit the formation of adduct 2, although both adducts are
      presumably derived from the 4-oxobutylating agent.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391621
TI  - Modeling cyanide release from nitriles: prediction of cytochrome P450 mediated
      acute nitrile toxicity.
AB  - A mechanism-based model for prediction of acute nitrile toxicity was developed
      using octanol-water partition coefficients (log P) and estimated rates of alpha
      hydrogen atom abstraction as variables. Relative rates of hydrogen atom
      abstraction were derived from differences in heats of formation for ground-state
      and radical geometries and radical ionization potentials. Calculated energies of
      activation for all potential sites of oxidation for a given nitrile were used to
      estimate partitioning of metabolites among multiple oxidative pathways. logP and
      the resulting corrected rate constants for alpha-carbon oxidation were effective
      variables in an acute toxicity model of structurally diverse nitriles. The
      pharmacokinetics of substrate disposition is discussed in the context of multiple
      metabolic pathways. Structure-toxicity relationships are also discussed.

PMID- 1391619
TI  - Comparative metabolism of dibenz[a,j]anthracene and 7-methyldibenz[a,j]anthracene
      in primary cultures of mouse keratinocytes.
AB  - The identification of several metabolites formed from dibenz[aj]anthracene
      (DB[aj]A) and 7-methyldibenz[aj]anthracene (7MeDB[aj]A) in primary cultures of
      mouse keratinocytes is presented. The metabolites were analyzed by coelution with
      known synthetic standards using high-pressure liquid chromatography. The
      metabolite identifications were further facilitated by comparisons of
      fluorescence excitation and emission spectra obtained for isolated metabolites
      with those for the synthetic standards. Both DB[aj]A and its 7-methyl analog were
      converted by mouse keratinocytes to the corresponding 3,4- as well as 5,6
      dihydrodiols. The 5,6-dihydrodiol of DB[aj]A was the major intracellular
      metabolite found at all time points up to 24 h. By 48 h, the relative proportion
      of both intracellular dihydrodiols had decreased, and they were found in
      approximately equal proportions. In contrast, 7MeDB[aj]A-3,4- dihydrodiol was the
      major intracellular metabolite of 7MeDB[aj]A at all time points examined up to 48
      h. The decreased intracellular retention of DB[aj]A-3,4-dihydrodiol was due, in
      part, to glucuronide conjugation and subsequent excretion of this metabolite. In
      this regard, both the 3,4- as well as the 5,6-dihydrodiols of DB[aj]A were found
      as glucuronides in the extracellular medium, whereas no such conjugates were
      detected extracellularly in cultures exposed to the 7-methyl derivative. The
      chromatographic profiles of cell- and medium-associated metabolites from both
      hydrocarbons also exhibited several other metabolite peaks that remain to be
      identified. The observed differences in dihydrodiol metabolism by mouse
      keratinocytes could explain, in part, the greater biological activity of
      7MeDB[aj]A relative to DB[aj]A.

PMID- 1391622
TI  - Characterization of urinary metabolites from [1,2,methoxy-13C]-2-methoxyethanol
      in mice using 13C nuclear magnetic resonance spectroscopy.
AB  - 2-Methoxyethanol (2-ME) is an industrial solvent that induces developmental and
      testicular toxicity in laboratory animals. Oxidation of 2-ME to 2-methoxyacetic
      acid (2-MAA) is required for the generation of these adverse effects. The urinary
      metabolites of 2-ME were investigated to characterize the fate of 2-ME and 2-MAA.
      13C NMR spectroscopy was used to detect and assign metabolites in the urine of
      pregnant CD-1 mice following administration of 250 mg/kg of [1,2,methoxy-13C]-2
      ME. Two-dimensional NMR methods were used to correlate signals from the labeled
      carbons in each 2-ME metabolite and to determine the number of hydrogens attached
      to each carbon. Structures were assigned from the NMR data together with
      calculated values of shift for biochemically feasible metabolites and by
      comparison to standards. Pathways involved in forming metabolites assigned in
      this study include transformation of 2-ME via ethylene glycol, conjugation with
      glucuronide or sulfate, and oxidation to 2-MAA. Additional metabolites were
      assigned that can be formed from further conversion of 2-MAA to glycine and
      glucuronide conjugates, as well as metabolites derived from the incorporation of
      2-methoxyacetyl CoA derivatives into intermediary metabolism. Elucidation of the
      further metabolism of 2-MAA may be important for understanding the mechanisms by
      which 2-ME induces adverse effects.

PMID- 1391620
TI  - Alkylation of DNA by 1,3-dialkyl-3-acyltriazenes: correlation of biological
      activity with chemical behavior.
AB  - The reactions of calf thymus DNA with four 1,3-dialkyl-3-acyltriazenes were
      studied alone or in the presence of pig liver esterase in pH 7.4 phosphate buffer
      for varying lengths of time. The best alkylating agent in the absence of esterase
      was determined to be 1,3-dimethyl-3-carbethoxytriazene (DMC), followed in order
      by 1-(2-hydroxyethyl)-3-methyl-3-carbethoxytriazene (HMC), 1-(2-hydroxyethyl)-3
      methyl-3-acetyltriazene (HMA), and 1-(2- chloroethyl)-3-methyl-3
      carbethoxytriazene (CMC). This order is the same as that for the rate of
      decomposition of the various acyltriazenes in pH 7.5 phosphate buffer. The extent
      of calf thymus DNA alkylation by CMC was found to be dependent on both the
      reaction buffer and the ionic strength of the medium. Alkylation by CMC alone in
      low ionic strength glycine buffer produced large quantities of 7-(2
      chloroethyl)guanine and 7-(2-hydroxyethyl)guanine. The products of DNA alkylation
      observed at neutral pH are consistent with N(2)-N(3) heterolysis of the triazene,
      resulting in the N(1) alkyldiazonium ion as the sole alkylating species. In the
      presence of esterase, CMC showed an enhanced rate of product formation.
      Furthermore, the product distribution shifted dramatically from mainly
      hydroxyethylation to predominantly methylation. CMC is postulated to undergo
      initial enzymatic deacylation, leading to two different alkyldiazonium ions which
      competitively alkylate DNA. HMC, on the other hand, was little affected by the
      esterase. The enzyme-catalyzed reaction showed a small increase in methylation
      and a smaller decrease in hydroxyethylation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391623
TI  - Dihydroxylated mercapturic acid metabolites of bromobenzene.
AB  - Bromobenzene is metabolized to electrophilic epoxides and quinones which
      covalently bind to protein sulfur nucleophiles, yet no quinone-derived
      mercapturic acid metabolites of bromobenzene have been reported. To search for
      them, phenobarbital-induced Sprague-Dawley rats were dosed (0.5-1.5 mmol/kg, ip)
      with either bromobenzene, 2-, 3-, or 4-bromophenol (BP), 3- or 4-bromocatechol
      (BC), or 2-bromohydroquinone (BHQ). Urine (0-24 h) was alkaline permethylated (2
      N NaOH/CH3I/80 degrees C), and the resulting thioanisole derivatives were
      analyzed by GC/MS. Three dimethoxythioanisoles and eight
      bromodimethoxythioanisoles were formed by alkaline permethylation of urine of
      rats treated with bromobenzene or 3-BP; alkaline permethylation of urine from
      rats in other treatment groups afforded characteristic subsets of these
      derivatives. The major thioanisole from all groups except 3-BC or 4-BC was 2,5
      dimethoxythioanisole, which arises from (2,5-dihydroxyphenyl)mercapturic acid.
      The latter was isolated from rat urine and is the first debrominated metabolite
      of bromobenzene reported to date. Its formation from both 4-bromophenol and BHQ
      requires two parallel mechanisms for bromine loss: (1) nucleophilic addition to
      1,4-benzoquinone formed by hydroxylative debromination of 4-bromophenol and (2)
      nucleophilic displacement of bromine from 2-bromo-1,4-benzoquinone by sulfur. The
      yields of quinone-derived mercapturic acids formed from bromobenzene are quite
      low (less than 1% of dose) compared to the high yields of epoxide-derived
      mercapturic acids (40% of dose). Potential reasons for this are discussed.

PMID- 1391624
TI  - An in vitro model for the in vivo mobilization of cadmium by chelating agents
      using 113Cd-NMR spectroscopy.
AB  - An in vitro method, based on 113Cd-NMR spectroscopy, that provides an alternative
      to the use of animals for an initial screening of cadmium antagonists is
      presented. The relative values of the effective stability constants of potential
      chelating antagonists for cadmium are estimated by using 113Cd-NMR spectroscopy
      to determine the concentrations of the cadmium species involved in appropriate
      competitive equilibria. This is accomplished via an examination of the
      competition between the proposed antagonist and EDTA (ethylenediaminetetraacetic
      acid) for cadmium-113; previously, EDTA has been shown to be capable of removing
      cadmium from such in vivo binding sites as metallothionein. The reactions proceed
      via the stepwise addition of three dithiocarbamate groups to the cadmium
      accompanied by the concurrent stepwise release of donor groups from the EDTA. The
      resulting 113Cd-NMR data allow for the determination of the overall stability
      constant for the complex formed between cadmium and N-methyl-D-glucamine
      dithiocarbamate, iminodiacetic acid dithiocarbamate, proline dithiocarbamate,
      sarcosine dithiocarbamate. The use of 113Cd-NMR spectroscopy has the potential
      for providing direct evidence on the effectiveness of chelate antagonists to
      compete with endogenous ligands for other toxic metal ions. This technique could
      prove very useful for other compounds that are not stable enough toward acid
      and/or base to be examined by standard titrimetric methods.

PMID- 1391626
TI  - Crystal and molecular structure of the doubly unsaturated dehydropeptide Ac-delta
      Phe-Ala-delta Phe-NH-Me.
AB  - The dehydropeptide Ac-delta Phe-L-Ala-delta Phe-NH-Me, containing two dehydro
      phenylalanine (delta Phe) residues, crystallizes from methanol/water in space
      group P2(1)2(1)2(1), with a = 12.508 (2), b = 12.746 (1) and c = 15.465 (9). In
      the crystalline state, the peptide chain assumes a right-handed 3(10)-helical
      conformation stabilized by two intramolecular hydrogen bonds, between the N
      terminal acetyl group and the NH of delta Phe3, and between the CO of delta Phe1
      and the NH of the C-terminal methylamide group, respectively. The two consecutive
      10-membered rings formed by the hydrogen bonds have torsion angles quite close to
      the standard values for type III beta-bends. delta Phe1 is located in the (i + 1)
      position of the first beta-bend, while delta Phe2 is located in the (i + 2)
      position of the other beta-bend. In the crystal, the molecules are linked head to
      tail by intermolecular hydrogen bonds to form long helical chains. The axes of
      the helices are parallel to the c axis, but neighboring helices run in
      antiparallel directions. This crystal packing is similar to the packing motifs
      frequently observed in Aib-containing peptides.

PMID- 1391625
TI  - Examination of diols and diol epoxides of polycyclic aromatic hydrocarbons as
      substrates for rat liver dihydrodiol dehydrogenase.
AB  - Dihydrodiol dehydrogenase (DD; EC 1.3.1.20) can suppress the formation of anti
      diol epoxides that arise from the metabolic activation of PAH by oxidizing their
      precursor trans-dihydrodiols to o-quinones [Smithgall, T.E., et al. (1988) J.
      Biol. Chem. 263, 1814-1820]. DD has also been found to reduce the mutagenicity of
      benz[a]anthracene (+/-)-anti-8,9-dihydrodiol 10,11-epoxide [(+/-)-anti-BADE] in
      the Ames test (Glatt, H.R., et al. (1982) Science 215, 1507-1509), suggesting
      that anti-diol epoxides are substrates for this enzyme. In this study, attempts
      have been made to demonstrate directly that diol epoxides of PAH are substrates
      for homogeneous DD. Spectrophotometric assays indicate that high concentrations
      of the stable anti-diol epoxides, naphthalene (+/-)-anti-1,2-dihydrodiol 3,4
      epoxide (10 mM) and (+/-)-anti-BADE (20 microM; limit of solubility) were not
      oxidized by micromolar concentrations of enzyme. By contrast, 20 microM (+/-)
      trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene [(+/-)-trans-BP-diol] was oxidized
      by 50-fold less enzyme. Using a reverse-phase high-performance liquid
      chromatography (RP-HPLC)-based assay [1,3-3H]-(+/-)-trans-BP-diol could be almost
      completely oxidized by DD in the presence of NADP+. Using a similar assay, [1,3
      3H]benzo[a]pyrene (+/-)-anti-7,8-dihydrodiol 9,10-epoxide [(+/-)-anti-BPDE], and
      unlabeled (+/-)-syn-BPDE and (+/-)-anti-BADE were tested as substrates for
      DD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391627
TI  - Hydration of DNA bases: analysis of crystallographic data.
AB  - We present a systematic analysis of water structure around nucleic acid bases. We
      have examined 28 crystal structures of oligonucleotides, and have studied the
      patterns of water around the four bases, guanine, cytosine, adenine, and thymine.
      The geometries of water positions were calculated up to 4.00 A from base atoms.
      We have found conformation-dependent differences in both the geometry and extent
      of hydration of the bases.

PMID- 1391628
TI  - Kinetics of folding of alpha alpha-tropomyosin subsequences.
AB  - The kinetics of folding random coils of alpha alpha-tropomyson (Tm) subsequences
      to two-chain coiled coils was studied by stopped-flow CD. Subsequences studied
      were those comprising residues 11-127 (11Tm127), 142-281 (142Tm281), 1-189
      (1Tm189), and 190-284 (190Tm284) of the parent 284-residue alpha-tropomyosin
      chain. Unlike the parent, subsequences 1Tm189 and 11Tm127 fold within the dead
      time of the instrument (less than 0.04 s). Like the parent, subsequences 142Tm281
      and 190Tm284 fold in two phases. In the fast phase, 45% and 32%, respectively, of
      the equilibrium helical content form. In the time-resolvable, first-order slow
      phase (k-1 = 2.7 s at 20 degrees C for 142Tm281 and k-1 = 2.0 s at 15 degrees C
      for 190Tm284), the remaining structure forms. Neither reduced 142Tm281 nor
      190Tm284 show any dependence of the rate on concentration, so chain association
      occurs in the fast phase. Like the parent 142Tm281 forms more helical content in
      the fast phase when cross-linked at C-190, and the remaining structure forms
      slowly with rate parameters similar to those of the reduced species. Comparison
      of the folding behavior of C- and N-terminal subsequences with that of the parent
      protein suggests that the slow phase in the parent is caused by a folding
      bottleneck somewhere nearer the C-terminus. However, rapid association and
      partial folding near the N-terminus is not necessary for prompt folding, since
      even 190Tm284 chains associate and partially fold very rapidly (less than 0.04
      s), and then complete the folding in seconds.

PMID- 1391629
TI  - Molecular structure of cyclo[-(D-Val-L-Hyi-L-Val-D-Hyi)2-] revealed by x-ray
      analysis.
AB  - The crystal structure of a synthetic analogue of valinomycin, cyclo[-(D-Val-L-Hyi
      L-Val-D-Hyi)2-] (octa-meso-valinomycin) (I) (C40H68N4O12.1.5.C4H8O2, M(r) =
      937.01 + 88.10), has been determined. Crystals grown from dioxane are monoclinic,
      space group P2(1)/a, with cell parameters a = 21.487 (8), b = 16.836 (5), c =
      16.089 (4) A, beta = 111.70 (4), and Z = 4. The atomic coordinates for
      nonhydrogen atoms were refined in the anisotropic thermal motion approximation. H
      atom positions were included in the structure factor calculations at their
      geometrically expected positions. Values of the standard and weighted R factors
      after refinement are 0.11 and 0.13, respectively. The conformation of the
      depsipeptide crystallized from dioxane is different from that crystallized from
      chloroform (II). The molecule adopts a rectangular shape with two type IV beta
      turns containing a hydrogen bond and possesses pseudorotational symmetry. The
      side chains are located on the molecular periphery. The orientation of the
      carbonyl groups of the molecule is not conducive for efficient metal-ion
      coordination and in the observed conformation cannot behave as an ionophore. In
      the crystal the molecules form infinite chains parallel to the c axis, and are
      stabilized by two intermolecular hydrogen bonds that are shorter and have better
      geometry than the intramolecular hydrogen bonds. A phi/psi plot for
      dodecadepsipeptides with a (DLLD)3 sequence has well-defined areas for Val and
      Hyi residues only in cases when the crystals have been grown from nonpolar or
      medium-polar solvents. The phi/psi plot for octadepsipeptides crystallized from
      chloroform (II) shows this behavior also.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391630
TI  - Vibrational CD studies of interchain hydrogen-bonded tripodal peptides.
AB  - The solution conformations of three trispeptides--L,L,L-1,3,5-C6H3[CH2NHCOCH(X)
      NHBoc++ +]3, X = CH3 (Ala) or CH2CH(CH3)2 (Leu), and L,L,L-N(CH2CH2NHCOCH[CH2
      CH(CH3)2]NHBoc)3--have been determined from their ir and vibrational CD (VCD)
      spectra in the NH stretching and carbonyl stretching regions in apolar solution.
      The compounds containing L-Leu are shown to occur primarily in a propeller
      conformation with C3 symmetry that is stabilized by interchain hydrogen bonds.
      Through application of the coupled oscillator model of VCD, a right-handed sense
      for the hydrogen-bonded chains in the propeller is deduced, in agreement with
      previous empirical force field calculations. The spectra also provide evidence
      for interchain association between two chains, resulting in a C10-ring. For
      chains not involved in interchain association, the spectra reveal the presence of
      C7-rings within a chain. The trispeptide containing L-Ala is found to occur
      primarily in a random form.

PMID- 1391631
TI  - Conformational states of a TT mismatch from molecular dynamics simulation of
      duplex d (CGCGATTCGCG).
AB  - The TT mismatch region in duplex d (CGCGATTCGCG) was studied using a 500-ps
      molecular dynamics (MD) simulation in water, and a series of 1-ps MD simulations
      and energy minimizations in vacuum. The DNA maintained its duplex structure,
      although the mismatch region showed significantly higher flexibility than the GC
      regions. The predominant conformation in the 500-ps MD simulation involved an
      average -42 degrees propeller twist between T6 and T'6, and a -22 degree buckle
      between A5 and T'7. One hydrogen bond was formed between T6 and T'6, and another
      between T6 and the O2 of T'7, with both Watson-Crick hydrogen bonds between A5
      and T'7 remaining intact. The minimizations resulted in conformations with the
      equivalent hydrogen-bonding pattern, as well as ones with "wobble pair" hydrogen
      bonds between T6 and T'6. However, the wobble pair conformation was found to be
      unstable in the water simulation.

PMID- 1391632
TI  - Flow linear dichroism spectra of four filamentous bacteriophages: DNA and coat
      protein contributions.
AB  - In this study, we have separated the contributions of DNA and protein to the
      absorption and linear dichroism (LD) of each of four phages: fd, IKe, Pf1, and
      Pf3. We have found that the DNA packaged in each of the phages is hypochromic
      relative to the purified single-stranded DNA, suggesting that bases are stacked
      in all of the phages. We have oriented the phages by flow and for the first time
      report the intrinsic LD from 320 to 190 nm for each of these phages. From the
      intrinsic LD of the phages and the isotropic absorption of the individual
      components, we have determined the reduced dichroism of the DNA within the phages
      and, subsequently, the maximum angle of inclination of the DNA bases (from the
      helix axis) for the packaged DNA. The maximum angles were 63 degrees and 64
      degrees for the DNAs of class I phages fd and IKe, respectively. The angles were
      significantly less, 51 degrees and 49 degrees, for the DNAs of the class II
      phages Pf1 and Pf3, respectively. Thus, the two classes of phage differ in the
      structures of their packaged DNA, the DNA bases of the class II phages being more
      parallel to the long axis of the phage than are the DNA bases of the class I
      phages.

PMID- 1391633
TI  - Crystal and molecular structure of the depsipeptide ionophore
      hexadecaisoleucinomycin, cyclo-[(D-Ile-L-Lac-L-Ile-D-Hyi)4-] (C80H136N8O24).
AB  - The crystal structure of a synthetic depsipeptide ionophore
      hexadecaisoleucinomycin, cyclo [-(D-Ile-L-Lac-L-Ile-D-Hyi)4-] (C80H136N8O24), has
      been determined by single crystal x-ray diffraction techniques. The crystals are
      orthorhombic, space group P2(1)2(1)2(1), number of molecules per unit cell z = 4,
      and cell parameters a = 11,195, b = 17.853, c = 54.835 A. The values of the
      standard (R) and weighted (Rw) discrepancy factors after refinement are 0.122 and
      0.135, respectively. The structure is characterized by an elongated bracelet form
      with a twofold axis of pseudosymmetry. It is stabilized by eight intramolecular 4
      ---1 hydrogen bonds between the amide C = O and N - H groups. The ester carbonyls
      are directed toward the inside of the molecule, their oxygen atoms forming an
      ellipsoidal internal cavity. The side chains are located on the molecular
      periphery. The conformational states of hexadecaisoleucinomycin in solution are
      discussed in the light of the data obtained.

PMID- 1391634
TI  - Studies of DNA dumbbells. I. Melting curves of 17 DNA dumbbells with different
      duplex stem sequences linked by T4 endloops: evaluation of the nearest-neighbor
      stacking interactions in DNA.
AB  - Seventeen DNA dumbbells were constructed that have duplex sequences ranging in
      length from 14 to 18 base pairs linked on the ends by T4 single-strand loops.
      Fifteen of the molecules have the core duplexes with the sequences 5'G-T-A-T-C-C
      (W-X-Y-Z)-G-G-A-T-A-C3', where (W-X-Y-Z) represents a unique combination of A.T,
      T.A, G.C, and C.G base pairs. The remaining two molecules have the central
      sequence (W-X-Y-Z) = A-C and A-C-A-C-A-C. These duplex sequences were designed
      such that the central sequences include different combinations of the 10 possible
      nearest-neighbor (n-n) stacks in DNA. In this sense the set of molecules is
      complete and serves as a model system for evaluating sequence-dependent local
      stability of DNA. Optical melting curves of the samples were collected in 25, 55,
      85, and 115 mM [Na+], and showed, regardless of solvent ionic strength, that the
      transition temperatures of the dumbbells vary by as much as 14 degrees for
      different molecules of the set. Results of melting experiments analyzed in terms
      of a n-n sequence-dependent model allowed evaluation of nine independent linear
      combinations of the n-n stacking interactions in DNA as a function of solvent
      ionic strength. Although there are in principle 10 possible different n-n
      interactions in DNA, these 10 are not linearly independent and therefore can not
      be uniquely determined. For molecules with ends, there are 9 linearly independent
      combinations, as opposed to circular or semiinfinite repeating copolymers where
      only 8 linear combinations of the 10 possible n-n interactions are linearly
      independent. The n-n interactions are presented as combinations of the deviations
      from average stacking for the 5'-3' base-pair doublets, delta Gi, and reveal
      several interesting features: (1) Titratable changes in the values of delta Gi
      with changing salt environment are observed. In all salts the most stable unique
      combination is delta G4 = (delta GGpC+delta GCpG)/2, and the least stable is the
      GpG/CpC stack, delta G2 = delta GGpG/CpC. (2) The chi 2 values of the fits of the
      evaluated delta Gi's to experimental data increased with decreasing [Na+],
      suggesting that significant interactions beyond nearest neighbors become more
      pronounced, particularly at 25 nM Na+.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1391635
TI  - Studies of DNA dumbbells. II. Construction and characterization of DNA dumbbells
      with a 16 base-pair duplex stem and Tn end loops (n = 2, 3, 4, 6, 8, 10, 14).
AB  - The preparation and characterization of DNA dumbbells that contain the 16 base
      pair duplex sequences 5'G-C-A-T-A-G-A-T-G-A-G-A-A-T-G-C3' (set 1) and 5'G-C-A-T-C
      A-T-C-G-A-T-G-A-T-G-C3' (set 2) are reported. The dumbbells of set 1 have the
      duplex stem nucleated on both ends by Tn (n = 2, 3, 4, 6, 8, 10, and 14) loops.
      The dumbbells of set 2 have Tn (n = 2, 4, 8, 10) end loops. For the molecules of
      set 1, effects of end loop size on the electrophoretic mobility, CD and UV
      absorbance spectra, and cleavage by restriction enzymes, were investigated.
      Effects of loop size on the CD spectra and restriction enzyme cleavage of the
      molecules of set 2 were also examined. Optical melting curves of the molecules of
      set 1 were collected as a function of sodium ion concentration from 30 to 120 mM.
      These investigations revealed that as loop size decreases, the electrophoretic
      mobilities, rates of enzyme cleavage, and optical melting temperatures increase.
      For end loops with at least three T's the observed increases are inversely
      proportional to loop size. The behavior of the dumbbell with T2 end loops departs
      from this linear dependence and is anomalous in every experimental context. For
      molecules with end loops comprised of at least four T's CD spectra were virtually
      indistinguishable. However, these spectra differed considerably from the CD
      spectrum of the T2-looped molecule. The CD spectrum of the dumbbell with T3 end
      loops displayed features common to the dumbbells with larger loops and T2 end
      loops. Thermodynamic evidence that the terminal G.C base pairs (bps) nucleating
      the T2 end loops were intact was obtained from a comparison of the melting
      temperature of this molecule with that of a DNA dumbbell containing the 14
      central bps of the set 1 duplex sequence linked instead by end loops comprised of
      the four base sequence, C-T-T-C. The tm of this latter molecule was determined to
      be 9 degrees C less than that of the former dumbbell assumed to contain a 16-bp
      stem and T2 end loops.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1391636
TI  - Studies of DNA dumbbells. III. Theoretical analysis of optical melting curves of
      dumbbells with a 16 base-pair duplex stem and Tn end loops (n = 2, 3, 4, 6, 8,
      10, 14).
AB  - Optical melting curves of seven DNA dumbbells with the 16 base-pair duplex
      sequence 5'G-C-A-T-A-G-A-T-G-A-G-A-A-T-G-C3' linked on both ends by Tn (n = 2, 3,
      4, 6, 8, 10, and 14) loops measured in 30, 70, and 120 mM Na+ are analyzed in
      terms of the numerically exact statistical thermodynamic model of DNA melting.
      The construction and characterization of these molecules were described in the
      previous paper (Amaratunga et al., 1992). As was recently reported for hairpins
      (T. M. Paner, M. Amaratunga, M. J. Doktycz, and A. S. Benight, 1990, Biopolymers,
      Vol. 29, pp. 1715-1734) theoretically calculated melting curves were fitted to
      experimental curves by simultaneously adjusting the parameters representing loop
      and circle formation to optimize the fits. The systematically determined
      empirical parameters provide evaluations of the free energies of hairpin loop
      formation delta Gloop (n) and single-strand circles delta Gcircle (N), as a
      function of end loop size, n = 2-14, and circle size, N = 32 + 2n. The dependence
      of these quantities on solvent ionic strength over the range from 30 to 120 mM
      Na+ was evaluated. An approximately analytical expression for the partition
      function Q(T) of the dumbbells was formulated that allowed a means for
      determining the transition enthalpy delta H degrees and entropy delta S degrees
      for every dumbbell, revealing the dependence of these quantities on loop size. In
      this multistate approach a manifold of partially melted intermediate microstates
      are considered and therefore no assumptions regarding the nature of the melting
      transitions (that they are two-state) are required. The transition thermodynamic
      parameters were also determined from a van't Hoff analysis of the melting curves.
      Comparisons between the results of the multistate analysis and the two-state
      van't Hoff analysis revealed significant differences for the dumbbells with
      larger end loops, indicating that the melting transitions of the larger looped
      dumbbells deviate considerably from two-state behavior. Results are then compared
      with published melting studies of much larger DNA dumbbells (D. B. Naritsin and
      Y. L. Lyubchenko, 1990, Journal of Biomolecular Structure and Dynamics, Vol. 8,
      pp. 1-13), of small hairpins (Paner et al., 1990; M. J. Doktycz, T. M. Paner, M.
      Amaratunga and A. S. Benight, 1990, Biopolymers, Vol. 30, pp. 829-845) and
      another dumbbell (A. S. Benight, J. M. Schurr, P. F. Flynn, B. R. Reid, and D. E.
      Wemmer, 1988) Journal of Molecular Biology, Vol. 200, pp. 377-399).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1391637
TI  - A semiempirical expression for the gel electrophoretic mobility of supercoiled
      DNA.

PMID- 1391638
TI  - The ever-evolving epidemiologic concepts of human immunodeficiency virus
      infections.
AB  - Human immunodeficiency virus infection has now reached epidemic proportions in
      both industrialized and nonindustrialized countries. Two preventive measures
      remain of questionable benefit: mandatory testing and partner notification.
      Sexually transmitted diseases and cervical ectopy may be risk factors for
      heterosexual transmission, now the most frequent mode of transmission of human
      immunodeficiency virus worldwide. Smokable freebase cocaine, the use of which is
      increasing in many cities in industrialized countries, is associated with
      acquisition of sexually transmitted diseases and human immunodeficiency virus
      infection. In addition to perinatal transmission of human immunodeficiency virus,
      postnatal transmission via breastfeeding has been demonstrated in association
      with a recent acquisition of human immunodeficiency virus by the mother.
      Intriguingly, in multiple pregnancies, first-born twins of human immunodeficiency
      virus-infected mothers could be at higher risk of infection than second-born
      twins. Nosocomial transmission of human immunodeficiency virus, both from
      infected patients to health professionals and from infected health professionals
      to patients, is a matter of concern and justifies preventive measures.

PMID- 1391639
TI  - Pelvic inflammatory disease.
AB  - Pelvic inflammatory disease is a common serious complication of the sexually
      transmitted pathogens Neisseria gonorrhoeae and Chlamydia trachomatis. There are
      more than 800,000 cases of pelvic inflammatory disease annually accounting for
      approximately 200,000 hospital admissions for acute and chronic infections. Early
      accurate diagnosis and treatment are essential to prevent the serious sequelae
      including ectopic pregnancy, tubal disease infertility, chronic pain, and
      disability requiring multiple hospitalizations and surgery. Although clinical
      models to aid in the diagnosis and management of pelvic inflammatory disease have
      been developed by numerous investigators, all have lacked the sensitivity and
      specificity to be helpful to the clinician. Laparoscopy, considered by many to be
      the "gold standard" for diagnosis, is underutilized, and the definition of pelvic
      infection differs between investigators. Improved patient compliance and safety
      may be seen if single-agent therapy for acute pelvic inflammatory disease becomes
      a reality. In a small prospective randomized study, oral ofloxacin was as
      effective as cefoxitin plus doxycycline for outpatient treatment of chlamydial
      and gonococcal pelvic inflammatory disease. Treatment of tuboovarian abscess
      appears to be successful with single agent and combination therapy. Risk factors
      for developing postabortion endometritis continue to be identified, and the most
      efficacious prophylactic antibiotic regimen has not been determined to date.

PMID- 1391642
TI  - Fertilization and early embryonic development.
AB  - Whether one carefully and meticulously records detailed observations in the
      laboratory, or jumps feet first into new and exciting areas of investigation,
      each scientist contributes to the advances being made in the control of human
      reproduction. The study of spermatozoa, oocytes, sperm-oocyte interaction,
      preembryo growth and development, and early pregnancy rewards us with
      breakthroughs in innovative technology and promotes paths of better
      understanding. One cannot search through the massive amounts of currently
      available literature without desiring to try "this" technique, expound on "that"
      one, take someone else's work a little further, or look at one's own results from
      a different angle. Presented here are some informative data, most published
      within the past year. Oocyte maturational competence and integrity, sperm
      function and quality, preembryo culture conditions, preembryo morphology, and
      ovarian age all emerge as factors important for interpreting a patient's chance
      of achieving pregnancy.

PMID- 1391641
TI  - Current technology of oocyte retrieval.
AB  - Transvaginal follicle puncture under sonographic control has become the method of
      choice for ovum retrieval worldwide. Because it is the current technology of the
      1990s, there are very few reports in the literature on other methods of oocyte
      retrieval. Furthermore, perhaps because of the simplicity of transvaginal
      follicle puncture under sonographic control, there are only a few reports on the
      technique itself in the current literature. This review classifies the papers on
      hand according to general studies of the subject, appropriate anesthesia,
      necessity of follicle flushing for oocyte retrieval, vaginal disinfection and the
      evaluation of the risk following transvaginal oocyte retrieval, and new
      techniques in connection with the harvesting of oocytes.

PMID- 1391640
TI  - New trends in combined use of gonadotropin-releasing hormone antagonists with
      gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction
      and assisted reproductive technologies.
AB  - The use of gonadotropin-releasing hormone agonists as adjunctive therapy with
      gonadotropins for ovulation induction in in vitro fertilization and other
      assisted reproductive technologies has become common clinical practice. With the
      recent advent of potent gonadotropin-releasing hormone antagonists free from the
      marked histamine-release effects that stymied earlier compounds, an attractive
      alternative method may be available. We have established the feasibility of
      combining gonadotropin-releasing hormone antagonist-induced inhibition of
      endogenous gonadotropins with exogenous gonadotropin therapy for ovulation
      induction in a nonhuman primate model. Here, the principal benefits to be gained
      from using the gonadotropin-releasing hormone antagonist rather than the
      gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary
      gonadotropin secretion without the "flare effect," which brings greater safety
      and convenience for patients and the medical team and saves time and money. We
      have also recently demonstrated the feasibility of combining gonadotropin
      releasing hormone antagonist with pulsatile gonadotropin-releasing hormone
      therapy for the controlled restoration of gonadotropin secretion and gonadal
      steroidogenesis culminating in apparently normal (singleton) ovulatory cycles.
      This is feasible only with gonadotropin-releasing hormone antagonists because,
      unlike gonadotropin-releasing hormone agonists, they achieve control of the
      pituitary-ovarian axis without down regulation of the gonadotropin-releasing
      hormone receptor system. This capacity to override gonadotropin-releasing hormone
      antagonist-induced suppression of pituitary-ovarian function may allow new
      treatment modalities to be employed for women who suffer from chronic
      hyperandrogenemia with polycystic ovarian disease.

PMID- 1391643
TI  - Male factor infertility and assisted reproductive technologies.
AB  - Male infertility has many facets that need to be evaluated in an initial
      screening. Once these are known, recommendations become clearer for aggressively
      pursuing assisted reproductive techniques. Progress has been made in defining
      more clearly the severe male factor: concentration less than 5 x 10(6) sperm/mL,
      motility less than 10%, morphology less than 4% normal forms (by strict
      criteria), and recovered swim-up sperm less than 1.5 x 10(6). Sperm preparation
      techniques may be improved by use of Percoll separation medium, and morphology
      may be used in prediction of cleavage rate in in vitro fertilization. Hopefully,
      these techniques will lead to more specific guidelines for successful use of
      assisted reproductive technology in male factor patients.

PMID- 1391644
TI  - Micromanipulation of gametes and embryos in preimplantation genetic diagnosis and
      assisted fertilization.
AB  - Recent advances in micromanipulation and biopsy of gametes and embryos have made
      it possible to develop new approaches for early genetic diagnosis and prevention
      of genetic disease and for treatment of severe male-factor infertility.
      Preimplantation diagnosis of a number of X-linked and autosomal recessive
      disorders has been performed, using polar body sampling and blastomere biopsy,
      coupled with polymerase chain reaction. Blastocyst biopsy has also been performed
      in human embryos; however, there has been no clinical application so far.
      Existing data have not shown any detrimental effect of micromanipulation and
      biopsy involved in the preimplantation development of the human embryo. The
      existing experience on micromanipulation of gametes (zona-opening procedures,
      subzonal sperm insertion, and sperm microinjection into the ooplasm) has also
      demonstrated the clinical usefulness in assisted fertilization, suggesting a
      possible selective application of various micromanipulation techniques and their
      combinations in male infertility.

PMID- 1391645
TI  - Cryopreservation of semen, oocytes, and embryos.
AB  - Human embryo cryopreservation is widely applied by programs of assisted
      reproductive technology. However, recent surveys have shown that relatively few
      in vitro fertilization programs in the United States substantially increase their
      per retrieval delivery rates through cryopreservation. While embryos may be
      successfully frozen and thawed at a range of developmental stages using several
      different cryoprotectants, the majority of in vitro fertilization programs use
      1,2 propanediol to freeze early (pronuclear four-cell) embryos. Ultrarapid
      freezing techniques are under continued study; they have not yet been shown to
      offer any clinical advantage over slow freezing protocols. Although interest in
      oocyte cryopreservation remains high, experimental evidence shows that cryoinjury
      to human oocytes results in chromosome sorting defects, reduced fertilization,
      and compromised embryonic development. Micromanipulation of mammalian oocytes
      appears to have no deleterious effect on subsequent cryopreservation.

PMID- 1391646
TI  - Oocyte donation.
AB  - Use of donor oocytes is becoming an increasingly important facet of assisted
      reproductive technology programs. Candidates for donor oocytes include women with
      premature ovarian failure or severe genetic disorders, women who respond poorly
      to human menopausal gonadotropin, and women older than 40 years who do not
      conceive with used of other therapies. The coordination of donor and recipient of
      oocytes is facilitated by pituitary desensitization of both parties using
      gonadotropin-releasing-hormone agonists. Pregnancy rates are much higher than
      that achieved with traditional in vitro fertilization and embryo transfer,
      possibly because of the young age of the donors and better endometrial
      receptivity.

PMID- 1391647
TI  - Endometrial receptivity and the luteal phase.
AB  - Endometrial receptivity to the implanting blastocyst determines whether pregnancy
      occurs. Whether fertilization is initiated in vivo or in vitro, the receptivity
      of the luteal-phase endometrium results from the input of interacting hormonal,
      growth, and immunologic factors. Endometrial adequacy for implantation has
      traditionally been assessed by the endometrial biopsy. Newer methods used to
      study the endometrium, such as ultrasound imaging and measurement of endometrial
      proteins, have increased our understanding yet have demonstrated the limits of
      our knowledge. This review is designed to analyze the available literature for
      concepts and scientific facts to aid in our understanding of the complex events
      required in preparation of a receptive endometrium. Special attention is focused
      on the effect of supraphysiologic levels of steroid hormones on the endometrium
      in ovulation induction. The effect of both embryo quality and luteal-phase
      support are also reviewed.

PMID- 1391648
TI  - Gamete and zygote intrafallopian transfers and related techniques.
AB  - Until recently, most authors reported superior results (ie, higher implantation
      and pregnancy rates) with gamete intrafallopian transfer (GIFT) and zygote
      intrafallopian transfer (ZIFT) compared with results using in vitro fertilization
      embryo transfer (IVF-ET). According to these investigators, the advantages of
      tubal over uterine transfer are related mainly to a stable tubal environment and
      a more appropriate arrival time of the embryo into the uterine cavity. However,
      more recently, the use of IVF-ET has been increasingly extended to etiologies
      other than tubal infertility. Indeed, the recent simplification of this technique
      and the achievement of pregnancy rates comparable to those obtained with tubal
      transfers have seriously questioned the value of ZIFT and any other type of tubal
      embryo transfer. As discussed in this review, the results obtained with various
      transfer procedures in nontubal infertility must still prove ZIFT to be a more
      effective procedure than IVF-ET. Efforts to develop transcervical methods of
      transfer to the tube have not translated into higher pregnancy rates than those
      with IVF-ET. On the other hand, laboratory conditions appear to affect embryos in
      ways not corrected by the tubal milieu. Negative effects of laboratory conditions
      on embryos are confirmed by differences in results between GIFT and ZIFT that are
      accentuated with age. The results obtained with GIFT in patients 40 years of age
      and older seem to emphasize not only the high compliance of the endometrial
      receptivity but also the relevance of the biologic potential of the embryos in
      the process of implantation at this age.

PMID- 1391650
TI  - Infectious diseases.

PMID- 1391651
TI  - In vitro fertilization.

PMID- 1391649
TI  - Ethical issues and controversies in assisted reproductive technologies.
AB  - The current ethical issues and controversies concerning in vitro fertilization
      revolve around micromanipulation of the gametes, cryopreservation of the
      fertilized ova, selective termination in multiple pregnancies, surrogacy, and
      gamete donation. At the basis of these ethical issues is the philosophic question
      of personhood, or the term "human person," and the consideration given to the
      normal weight that is ascribed to the various forms of living matter that are
      found in the process of development after human spermatozoa have been placed
      together with harvested oocytes in the petri dish. The papers of very special
      importance and special importance written during the past year on these ethical
      problems are listed and classified. The summaries of their arguments and
      positions on these problems are enumerated.

PMID- 1391652
TI  - Overview of selected health surveys in Canada, 1985 to 1991.

PMID- 1391653
TI  - Short-term hospital care for psychiatric illness among seniors.
AB  - This study focuses on recent changes in hospital use by seniors (aged 65 or over)
      who have been treated as inpatients in general and psychiatric hospitals for less
      than one year with functional psychoses and clinical disorders. The data analyzed
      are hospital separations for the age groups 65 to 74, 75 to 84, and 85 and over,
      for the period 1980-89. The data are derived from hospital morbidity statistics
      submitted annually to Statistics Canada by the provincial ministries of health.
      Age-specific separation rates for the age groups 75 to 84, and 85 and over
      increased during 1980-89. However, for the age group 65-74, the rates were fairly
      stable and in some instances decreased. These increases in short-term
      hospitalization of the seniors 75 and over are evidence of the appreciation of
      their treatability and of the improved recognition of these disorders in this age
      group. Adverse reactions to prescription drugs resulting in psychiatric symptoms
      may also be a factor in the increasing hospitalization rates. The largest
      increases in age-specific rates and bed days were for the age group 85 and over.
      For this age group, the separation rates were higher for men than women. In this
      age group in 1986, a higher proportion of women than men lived in institutions.
      For seniors living outside institutions, a larger percentage of men than women
      lived alone. This situation likely promotes more social isolation for men than
      women, and may be an important factor in the higher hospitalization rates among
      men.

PMID- 1391654
TI  - Development of health expectancy indicators: meeting of the International Network
      on Health Expectancy (REVES).

PMID- 1391656
TI  - Births and birth rates, Canada, 1990.

PMID- 1391655
TI  - Place of birth and ethnic status: factors associated with smoking prevalence
      among Canadians.
AB  - The prevalence of smoking is lower among foreign-born (16%) than among native
      born Canadians (25%). In addition, foreign-born smokers smoke fewer cigarettes a
      day than the native-born. Foreign-born Canadians also tend to smoke cigarettes
      with a lower tar yield. The differences in the smoking behaviour of foreign-born
      and native-born Canadians suggest that the foreign-born may be at lower risk from
      smoking related morbidity and mortality. National smoking rates conceal wide
      variations in smoking prevalence by ethnic group. The highest smoking rates in
      Canada are found among Canadian Aboriginals. About 59% of Aboriginal Canadians
      smoke on a regular basis. In contrast, only 11% of Asian Canadians smoke
      regularly. These marked differences in smoking rates among ethnic groups are an
      argument for addressing the unique behaviour of each ethnic group within existing
      health promotion programs. Four out of ten smokers (42%) attempts to quit smoking
      during the course of a year. This percentage does not vary much by gender or by
      foreign-born/native-born status. The high percentage of smokers who attempt to
      quit during a year probably reflects the combined impacts of smoking prevention
      programs, increased taxation on cigarettes, and smoking restrictions on smoking
      in the workplace and in public settings.

PMID- 1391657
TI  - Historical publication highlights: selected marriage statistics, Canada, 1921
      1990.

PMID- 1391658
TI  - The November 15, 1991, workshop on record linkage methodology.

PMID- 1391659
TI  - Marriages: Canada, 1990.

PMID- 1391660
TI  - Residential care facilities--statistical indicators.

PMID- 1391661
TI  - Expression and secretion of an assembled tetrameric CH2-deleted antibody in E.
      coli.
AB  - We have expressed in E. coli a functional assembled antibody variant that is
      secreted into the media. The antibody variant is a CH2-deleted chimeric antibody
      14.18, which was previously shown to be a potentially useful reagent for
      radioimmunodetection of human tumors. The bacterial expression vector contains a
      dicistronic unit comprised of a L-chain cDNA and a CH2-deleted H-chain cDNA. For
      translocation across the bacterial membranes, we have replaced the natural signal
      peptides of the H and L chains with the signal peptide of the bacterial protein
      pectate lyase B. When expressed in the JM105 host under the control of the trp
      lac promoter, the products were secreted into the M9 growth media to about 350
      micrograms/L. The secreted antibody, which can be readily purified from the media
      without any denaturation or renaturation steps, retains antigen-binding activity.
      SDS-PAGE and nondenaturing size exclusion high-pressure liquid chromatography
      showed that it is a mixture of assembled HL and fully assembled H2L2. In H2L2,
      inter-H chain disulfide bonds are not formed, and the two HL half-molecules are
      likely held together by the trans interaction between the two CH3 domains.

PMID- 1391663
TI  - Preparation of genetically engineered monoclonal antibodies for human
      immunotherapy.
AB  - Production of human monoclonal antibodies (MAbs) of predefined specificity using
      conventional hybridoma technology has proved to be difficult. Immunotherapeutic
      intervention in humans with rodent MAbs, however, is disadvantageous because of
      the antigenicity of these proteins and may result in human antibody responses
      against this foreign agent. To circumvent this problem, recombinant DNA
      techniques have been developed to transplant the specificity of a rodent MAb into
      a human antibody. Two basic approaches are being employed: first, combining
      rodent MAb variable regions with human constant regions; and more recently,
      "reshaping" human MAbs by grafting complementarity-determining regions (CDR) into
      the human antibody framework. These humanized MAbs can now be used to study human
      Fc-dependent effector mechanisms in detail, which seems essential to optimize
      potential in vivo application.

PMID- 1391662
TI  - Stable expression of cloned human antibody genes in murine myeloma cells.
AB  - Human monoclonal antibodies (MAbs) offer potential advantages over murine MAbs
      for therapy because they are not likely to elicit immune responses and are
      expected to interact more efficiently with the human immune system to activate
      therapeutically useful functions. Traditional methods for obtaining human MAbs
      (i.e., immortalization of B cells by cell fusion or transformation) can result in
      low and unstable antibody secretion. Recently, methods have been devised for
      direct cloning of human variable region genes via polymerase chain reaction and
      phage combinatorial libraries. Both types of human MAb production can benefit
      from expression systems that support the stable, high-level antibody secretion
      required for therapeutic use. Using an existing human-derived hybridoma that
      secretes a human IgM antibody as a convenient source of antibody genes, we have
      demonstrated that cloned human antibody genes can be efficiently expressed in
      murine myeloma cells and that cell lines with properties suitable for large-scale
      economical production can be obtained. We were unable to detect any differences
      between the antibodies produced by the original hybridoma and the engineered cell
      line. In addition, we were able to express an IgG form of the antibody, showing
      that expression of a recombinant human antibody need not be limited to the
      original antibody class.

PMID- 1391664
TI  - Rescue and expression of human immunoglobulin genes to generate functional human
      monoclonal antibodies.
AB  - Human monoclonal antibody production has been hampered for many years by the
      instability of cell lines and low levels of expression of the antibodies. We
      describe here the rescue of human immunoglobulin genes utilizing micro-mRNA
      preparation from a small number of human hybridoma cells and conventional cDNA
      cloning. This allows cloning and immediate high-level expression from full-length
      human heavy and light chain cDNA molecules and provides a mechanism to rescue
      whole human monoclonal antibodies of proven efficacy.

PMID- 1391665
TI  - Variable region differences affect antibody binding to immobilized but not
      soluble antigen.
AB  - We have examined the antigen binding characteristics of two chimeric IgG1
      antibodies that differ only in the heavy chain variable region. Antibodies 10B
      and B11 were expressed from two different anti-(Tyr,Glu)-Ala-Lys murine VH genes
      joined to human IgG1 constant region genes in a murine anti-(Tyr,Glu)-Ala-Lys
      heavy chain loss variant hybridoma. The binding characteristics of the antibodies
      to (Tyr,Glu)-Ala-Lys and to a peptide conjugate, CYYYEEEEY:BSA, were measured in
      solution and solid phase assays. The antibodies exhibited similar affinities and
      binding characteristics when assayed in solution assays. However, when we
      measured binding of antibodies to immobilized antigens, we found that antibody
      affinity depended on the epitope density in the immobilized immune complexes. The
      binding of antibody 10B and of B11 to immobilized (Tyr,Glu)-Ala-Lys and to
      CYYYEEEEY:BSA were similar at high antigen density, but antibody B11 bound less
      well at lower antigen density. Fab fragments of 10B bound to immobilized
      (Tyr,Glu)-Ala-Lys and CYYYEEEEY:BSA, but Fab fragments of B11 did not bind to
      (Tyr,Glu)-Ala-Lys and bound less well to CYYYEEEEY:BSA than 10B Fabs.

PMID- 1391666
TI  - Nutritional patterns and weight change in Alzheimer patients.
AB  - A nutritional study of 100 patients enrolled in an active geriatric outpatient
      teaching program was conducted to document the clinical impression of weight loss
      in Alzheimer's disease. All new patients were asked to complete a questionnaire
      on nutrition. Patients were evaluated by a geriatrician, then categorized using
      DSM-III and NINCDS-ADRDA criteria. There were 34 Alzheimer patients and 60
      nondemented patients with an average weight of 56.2 kgs and 66.1 kgs,
      respectively (p less than .002). Of the Alzheimer group, 44% reported weight loss
      in the past five years compared with 37% of the nondemented group, despite a
      concomitant increase in food intake in 35% versus 7%, respectively. On a one-year
      follow-up, 92% of Alzheimer patients lost weight, whereas 57% of the nondemented
      patients actually gained weight. The increase in reported food intake, with a
      significant concomitant weight loss, raises some challenging questions as to the
      existence of a hypermetabolic state in Alzheimer's disease.

PMID- 1391667
TI  - Memory improvements and pharmacological treatment: a method to distinguish direct
      effects on memory from secondary effects due to attention improvement.
AB  - Chronic cerebrovascular disturbances of the aged are characterized by a decline
      of attention. When these patients undergo pharmacological treatment, it is very
      difficult to distinguish between a direct benefit and/or a secondary effect on
      memory resulting from attention improvement. In our study we have proposed and
      evaluated a new method for identifying the different components of therapeutic
      efficacy on memory and attention in chronic cerebrovascular patients. This method
      is based on the use of the Randt Memory Test, traditional scores of memory
      efficiency (Acquisition, Recall, and a combined index), and the RMT three-factor
      scores derived from a structural model of memory functioning. The three scores
      have been called Encoding and Organization, Cognitive Efficiency, and Attention
      Efficiency. Participants were 96 selected chronic cerebrovascular patients
      treated in a double-blind study for 12 weeks with dihydroergocristine versus
      placebo. While changes in both acquisition and recall scores were related to the
      treatment, only changes of the Encoding and Organization factor scores were
      systematically related to therapy. Changes in Attention Efficiency were
      positively related to therapy only in proportion to the degree of cerebrovascular
      impairment.

PMID- 1391669
TI  - Geriatric psychopathology: an American perspective on a selected agenda for
      research.
AB  - The authors present an overview of research questions related to psychopathology
      in elderly patients. Specific research questions in the areas of organic mental
      disorders, affective disorders, personality disorders, anxiety disorders,
      psychotic disorders, and substance abuse are presented. Clinical investigators
      are encouraged to pursue some of these specific questions in order to facilitate
      diagnosis and to develop specific effective treatment strategies for
      psychopathology in older patients.

PMID- 1391668
TI  - Applying cognitive-behavioral psychotherapy to the chronically ill elderly:
      treatment issues and case illustration.
AB  - A large percentage of older adults must endure at least one chronic medical
      illness. Clinically significant depression and anxiety are common among these
      patients. Specific psychotherapy approaches as well as adaptations required to
      address the unique issues of this population have not been delineated in the
      literature. We outline a cognitive-behavioral therapy approach and discuss five
      treatment issues we have found to be important for this population. These issues
      include: (1) resolving practical barriers to participation; (2) accepting
      depression as a separate and reversible problem; (3) limiting excess disability;
      (4) counteracting the loss of important social roles and autonomy; and (5)
      challenging the perception of being a "burden." A case study of a chronic
      obstructive pulmonary disease (COPD) patient with depression is presented and
      recommendations for future research are suggested.

PMID- 1391670
TI  - Moving from the question of efficacy to the question of therapeutic relevance: an
      exploratory reanalysis of a controlled clinical study of 130 inpatients with
      dementia syndrome taking piracetam.
AB  - The authors reanalyzed previously published data from a prospectively randomized,
      placebo-controlled, double-blind phase-III study of 130 inpatients with dementia
      syndrome. The patients in the study had been diagnosed as having suffered from
      organic brain syndrome (ICD 290), which is the core syndrome of dementia (so
      called dementia syndrome) for at least two years. They were treated with
      piracetam for three months at a dose level of 4,800 mg/d. These data were
      reexamined in order both to survey the extent of drug-related improvement and
      response rates when assessed at different levels and to investigate the
      comparability of efficacy in subgroups suffering from either senile dementia of
      the Alzheimer type or multi-infarct dementia. Three scales were used for the
      assessment of efficacy. They were the CGI, or Clinical Global Impression,
      completed by the physicians; the SCAG, or Sandoz Clinical Assessment Geriatric,
      used by clinical psychologists; and the BGP, or Beurteilungsskala fur
      Geriatrische Patienten (Evaluation Scale for Geriatric Patients), employed by the
      nursing staff. The Syndrome-Kurztest (SKT) and Benton tests served to measure
      performance. The items and subscores of the SCAG and the SKT were highly
      intercorrelated at baseline, forming a common factor fairly independent of the
      information gained by BGP. This suggests that merely using different kinds of
      information-gathering methods, i.e., clinical scales and performance tests,
      completed by different groups of observers, does not automatically result in
      nonredundant comprehensive information. When using the most conservative response
      criterion of individual improvement, i.e., at least one baseline standard
      deviation, treatment with piracetam showed statistically significant (pe less
      than .001) explorative response rates of 50% and above in three out of four
      target variables, as compared to the 0 to 6% obtained with placebo. CGI was used
      as descriptive variable. Again, using this response criterion from a separate
      analysis of diagnostic subgroups, as matched by the median of the patients'
      Hachinski Ischemic Scale scores, it does not appear that piracetam's efficacy for
      patients with senile dementia of the Alzheimer type (SDAT) varies with its
      efficacy for patients with multi-infarct dementia (MID).

PMID- 1391671
TI  - A double-blind comparison of the effects of temazepam and triazolam on residual,
      daytime performance in elderly insomniacs.
AB  - Benzodiazepine hypnotic medications are widely prescribed for elderly patients,
      but there is a paucity of information available concerning the residual cognitive
      and psychomotor (the morning-after) effects of these drugs. We compared two
      commonly used hypnotics--temazepam and triazolam--in a double-blind, placebo
      controlled, single-dose study with community-dwelling healthy elderly with a DSM
      III-R diagnosis of primary insomnia. Forty-five subjects over the age of 65 (mean
      age 72.23, SD = 4.44) qualified for the study. Subjects were randomly assigned to
      one of five treatment groups (placebo, triazolam 0.125 mg., triazolam 0.25 mg.,
      temazepam 15 mg., and temazepam 30 mg.). Neuropsychological testing was completed
      at baseline and 12-14 hours after the dosing. Patients were evaluated with a
      variety of tests that measured attention, concentration, motor speed, immediate
      memory, and learning of new information. Separate repeated measured analyses of
      variance were performed to assess the significant changes among the five
      treatment groups. We found improved performance or no change in all the measures
      for all medication groups except for impairment of performance on a serial
      learning task for both high-dose medication groups. The significance of these
      results and the need for further research in elderly insomniacs is discussed.

PMID- 1391672
TI  - Assessing Alzheimer severity with a global clinical scale.
AB  - Diagnosis of dementia needs to be complemented by precise determination of
      disease severity across the broad spectrum of disease progression. The Mini
      Mental State Exam (MMS), the Activities-of-Daily-Living assessment (ADL) and the
      Clinical Dementia Rating scale (CDR) were modified for direct comparability and
      administered to 112 outpatients and 45 nursing home residents with a range of
      dementia severity from mild to profound. The scales showed the highest
      correlations for the probable Alzheimer's disease patient group (62) (Global
      Assessment of Dementia; GAD vs. ADL: r = 0.91; Extended Mini-Mental Assessment;
      EMA vs. GAD: r = 0.91; ADL vs. EMA: r = 0.86). For these patients, scores on the
      individual scales tended to be similar. Disparity among the three scores for
      individual cases was associated with the presence of comorbidities. The high
      correlations and correspondence among these scales demonstrate their reliability,
      validity, and utility in the assessment of dementia severity. The use of an
      average of these measures, with their increased precision, may give a more
      accurate indication of dementia severity over a broader range of impairment.

PMID- 1391673
TI  - Psychogeriatrics--an interdisciplinary specialty.

PMID- 1391674
TI  - Relationships among the symptoms of the elderly as revealed by multivariate
      analysis: a preliminary study.
AB  - One hundred and sixty-eight elderly subjects in a geriatric hospital and the
      adjoining nursing home were examined in a study of relationships among the items
      of Hasegawa's dementia scale. A three-dimensional model using multivariate
      analysis demonstrated the relationships among items. The results led to the
      identification of six clinical groups determined by the presence of stroke and
      the score on the dementia scale. Nonstroke subjects of middle intellectual level
      had disturbances of memory and orientation. This group fell into two categories
      during the course of a five-year follow-up study: severe dementia and
      intellectual deterioration. Retrospective multivariate analysis results suggested
      that features characteristic of the severe intellectual deterioration group were
      earlier disturbances of orientation and distant memory. This statistical method
      uses only objective clinical data in order to avoid subjective and, often, biased
      judgments.

PMID- 1391675
TI  - Longitudinal changes in computerized EEG and mental function of the aged: a nine
      year follow-up study.
AB  - Computer-analyzed EEG data and mental functions of the healthy aged (28 survivors
      and 20 nonsurvivors) were followed for nine years in a study of their
      relationship with age and longevity. The study revealed that decrease in fast
      waves occurred from early senescence. The slowing of EEG, the increase in theta
      waves, and the decrease in alpha frequency became obvious in late senescence,
      after the late 70s or beyond 80 years. The amount of alpha waves was maintained
      until the early 80s. The decline of mental functions occurred with the slowing of
      EEG in late senescence. The slowing of EEG and the lowered scores of
      psychometrics were closely related to the longevity of life, comparing the
      survivors and nonsurvivors in retrospect.

PMID- 1391676
TI  - Usefulness of the Neurobehavioral Cognitive Status Examination in the
      hospitalized elderly.
AB  - A prospective pilot study compared the Neurobehavioral Cognitive Status
      Examination (NCSE) to the Folstein Mini-Mental State Examination (MMSE) to
      determine the usefulness of the NCSE as a cognitive screen in a geriatric
      inpatient population. All patients directly admitted to the geriatric evaluation
      and treatment unit (GETU) of a university teaching hospital over a two-and-a-half
      month period were eligible for the study, in which 42% participated. Within 72
      hours of admission, patients were given the MMSE and the NCSE in a nonrandom
      order by a trained psychologist and a structured interview by a psychiatrist. The
      ability of the NCSE to detect global cognitive impairment was compared to the
      MMSE and psychiatrist's assessment. Differences in sensitivity were examined by
      discordant pair analysis. The psychiatrist's determination of the presence of
      cognitive impairment was used as the criterion standard. Comparisons of the MMSE
      and NCSE, respectively, revealed the following: sensitivity 83% versus 100%;
      specificity 78% versus 11%; positive predictive value 83% versus 43%; and
      negative predictive value 78% versus 100%. Seven patients who were cognitively
      impaired by the NCSE were not impaired by the MMSE (p less than 0.05 by
      discordant pair analysis). The time of administration for the two tests was
      significantly shorter for the MMSE (14.75 +/- 5.7 minutes) than for the NCSE
      (38.9 +/- 12.9 minutes). The NCSE was found to be more sensitive than the MMSE in
      detecting cognitive impairment among geriatric inpatients, but its specificity
      and positive predictive values were lower. Beyond this pilot study, additional
      work examining the utility of the NCSE in other geriatric settings and for
      different purposes (e.g., as part of comprehensive assessment) needs to be
      performed.

PMID- 1391677
TI  - Prediction of the volume of distribution of 7-hydroxycoumarin in man from in
      vitro and ex vivo data obtained in rat.
AB  - The essential parameter to estimate the first dose size of a drug in man is the
      volume of distribution. For a drug that has never been used in man before,
      estimates of the volume of distribution can only be obtained from animals and in
      vitro data. The purpose of this study was to compare various approaches presented
      in the literature for predicting the volume of distribution at steady state (VSS)
      and the terminal phase volume of distribution (Vd beta) in man. A lipophilic
      active metabolite of coumarin, 7-hydroxycoumarin (7OHC), was selected for this
      investigation. This compound is extensively metabolized in both the central and
      peripheral compartments. Of the six methods evaluated, only an empirical
      allometric approach yielded a reasonable estimate of VSS. All methods
      underestimated VSS and none of the applicable methods were able to predict Vd
      beta. The reason for this discrepancy may be due to the fact that the calculation
      of VSS in man was done assuming elimination from the central compartment.

PMID- 1391678
TI  - Influence of probenecid and paracetamol (acetaminophen) on zidovudine
      glucuronidation in human liver in vitro.
AB  - The effects of probenecid and paracetamol on zidovudine glucuronidation were
      investigated, in vitro, using human liver microsomal preparations. The presence
      of probenecid in the incubation medium significantly reduced the maximum reaction
      velocity for zidovudine glucuronide formation by more than 60 per cent, and the
      Km was reduced by 47 per cent, suggesting an uncompetitive inhibition of
      zidovudine glucuronidation. In contrast, paracetamol had no significant effect on
      zidovudine glucuronidation. The maximum reaction velocity for zidovudine
      glucuronide formation and the Km were unchanged when paracetamol (5 mM) was
      present in the incubation medium. The effects of probenecid and paracetamol on
      zidovudine metabolism in vitro correlates closely with those observed in vivo.
      The in vitro system of human liver microsomes may have a useful role in
      predicting the possible interaction of other drugs with zidovudine metabolism.

PMID- 1391679
TI  - Distribution of carbamazepine and its epoxide in blood compartments in adolescent
      and adult epileptic patients.
AB  - Carbamazepine (CBZ) used in the treatment of epilepsy, is metabolized in man to
      an active metabolite: carbamazepine 10-11 epoxide (CBZ-E). CBZ and CBZ-E
      concentrations in the different blood compartments (plasma ultrafiltrate, plasma
      proteins, and red blood cells (RBC)) of epileptic patients on CBZ monotherapy
      were assessed using HPLC. The highest CBZ and CBZ-E level to dose ratios were
      observed in the RBC. For CBZ and CBZ-E significant correlations were found
      between some blood compartments particularly between RBC and plasma
      ultrafiltrate. The measurement of CBZ and CBZ-E in all blood compartments may be
      interesting in uncontrolled patients and in patients presenting side-effects
      which cannot be explained by total plasma concentration values.

PMID- 1391680
TI  - Studies on the intravenous pharmacokinetics in rabbit and in vitro protein
      binding of two new salts of erythromycin: erythromycin maltobionate and
      erythromycin fumarate.
AB  - Pharmacokinetics in rabbits following intravenous administration and in vitro
      protein binding were studied for two new salts of erythromycin (erythromycin
      maltobionate and erythromycin fumarate). Serum erythromycin levels following
      intravenous injection were described by two compartment model kinetics, and
      values for the distribution volume of the central compartment, the peripheral
      compartment and overall distribution volume were calculated. The elimination half
      lives of erythromycins in serum were 83 min, 168 min, and 103 min for
      erythromycin maltobionate, erythromycin fumarate, and erythromycin lactobionate
      (reference standard), respectively. The erythromycin salts were highly (c. 90 per
      cent) protein bound, but the binding was found to be reversible. Differences in
      the pharmacokinetic parameters after administration of equivalent doses of the
      salts, indicate possible variation in efficacies of different salts.

PMID- 1391682
TI  - Extended least squares curve fitting: a comparison of SIPHAR and MKMODEL.
AB  - SIPHAR and MKMODEL in their extended least squares modes have been compared when
      fitting a triexponential declining function to simulated data. The data were
      simulated on SAS incorporating normally distributed random error, having
      coefficients of variation (CV) of 5, 10, 15, and 25 per cent. At each error level
      100 data sets, consisting of 21 data pairs, were simulated. Non-parametric tests
      were used to compare the accuracy and precision of the estimates produced by the
      packages. The comparison was repeated with two different sets of exponent values
      incorporating error at the 15 per cent level. MKMODEL was also compared to ELSFIT
      and ELSMOS at the same error level. SIPHAR was consistently less accurate and
      less precise than MKMODEL in estimating the structural model parameters. SIPHAR
      was also sensitive to the concentration units used for the input data. Estimates
      of the variance model power produced by SIPHAR were very variable while those
      from MKMODEL covered a much tighter range. For both packages there was generally
      a linear increase in the CV on each mean parameter estimate with increase in the
      CV on the error model. Good agreement was observed between MKMODEL, ELSFIT, and
      ELSMOS. The presence of an additive constant in the variance model used in SIPHAR
      was shown to be responsible for its poorer accuracy and precision.

PMID- 1391681
TI  - Pharmacokinetics and metabolism of codeine in humans.
AB  - Codeine (30 mg phosphate) was metabolized by eight human volunteers to the
      following six metabolites: codeine-6-glucuronide 81.0 +/- 9.3 per cent,
      norcodeine 2.16 +/- 1.44 per cent, morphine 0.56 +/- 0.39 per cent, morphine-3
      glucuronide 2.10 +/- 1.24 per cent, morphine-6-glucuronide 0.80 +/- 0.63 per
      cent, and normorphine 2.44 +/- 2.42 per cent. Two out of eight volunteers were
      unable to O-dealkylate codeine into morphine and lack therefore the cytochrome
      P450 IID6 isoenzyme. The half-life of codeine was 1.47 +/- 0.32 h, that of
      codeine-6-glucuronide 2.75 +/- 0.79 h, and that of morphine-3-glucuronide 1.71 +/
      0.51 h. The systemic clearance of codeine was 2280 +/- 840 ml min-1, the renal
      clearance of codeine was 93.8 +/- 29.8 ml min-1, and that of codeine-6
      glucuronide was 122 +/- 39.2 ml min-1. The plasma AUC of codeine-6-glucuronide is
      approximately 10 times higher than that of codeine. Protein binding of codeine
      and codeine-6-glucuronide in vivo was 56.1 +/- 2.5 per cent and 34.0 +/- 3.6 per
      cent, respectively. The in vitro protein binding of norcodeine was 23.5 +/- 2.9
      per cent; of morphine, 46.5 +/- 2.4 per cent; of normorphine, 23.5 +/- 3.5 per
      cent; of morphine-3-glucuronide, 27.0 +/- 0.8 per cent; and of morphine-6
      glucuronide, 36.7 +/- 3.8 per cent.

PMID- 1391683
TI  - Nobel Lecture. Nuclear magnetic resonance Fourier transform spectroscopy.

PMID- 1391684
TI  - 6-Dimethyl amino purine and 2-amino purine inhibit the induction of expression of
      milk protein genes by prolactin.
AB  - Two protein kinase-inhibitors, 6-dimethyl amino purine and 2-amino purine
      inhibited induction of beta-casein synthesis by prolactin when added to the
      culture medium of rabbit mammary explant and cells. The accumulation of the mRNA
      for alpha s1- and beta-caseins and for whey acidic protein did not take place in
      the presence of the inhibitors whereas beta-actin mRNA concentration was not
      altered. In the same experimental conditions, H7, an inhibitor of protein kinase
      C and, to a lower extent, of protein kinase A did not prevent prolactin from
      acting. These data suggest for the first time that specific protein kinases are
      involved in the transduction of the prolactin signal to milk protein genes.

PMID- 1391685
TI  - Seasonal commitment of HMGCoA reductase activity to vitellogenin production.
AB  - In female frogs (Rana Esculenta) during gametogenesis the cholesterol synthesized
      in the liver by 3-hydroxy-3-methylglutaryl coenzyme A reductase is mostly
      exported into the blood and taken up by the oocytes. In order to understand the
      fate of the neosynthesized cholesterol, female and male frogs and estrogenized
      male controls were injected with the labelled precursor 14C mevalonate. In
      females and in estrogenized controls, mevalonate-derived radioactivity is found
      in a plasmatic lipoprotein that has been identified as vitellogenin by
      immunological detection. The increased 3-hydroxy-3-methylglutaryl coenzyme A
      reductase activity present in females in Fall is likely to be committed to
      provide cholesterol for the lipidation of this cholesterol-rich protein.

PMID- 1391686
TI  - Changes in membrane permeability during Semliki Forest virus induced cell fusion.
AB  - The infection of Aedes albopictus cells by Semliki Forest virus (SFV) is a non
      lytic event. Exposure of infected cells to mildly acidic pH (less than 6.2) leads
      to syncytium formation. This polykaryon formation is accompanied by an influx of
      protons into the cells (Kempf et al. Biosci. Rep. 7, 761-769, 1987). We have
      further investigated this permeability change using various fluorescent or
      radiolabeled compounds. A significant, pH dependent increase of the membrane
      permeability to low molecular weight compounds (M(r) less than 1000) was observed
      when infected cells were exposed to a pH less than 6.2. The pH dependence of the
      permeability change was very similar to the pH dependence of cell-cell fusion.
      The permeability change was sensitive to divalent cations, protons and anionic
      antiviral drugs such as trypan blue. The nature of this virus induced, pH
      dependent permeability change is discussed.

PMID- 1391687
TI  - The definitions of metabolic control analysis revisited.
AB  - Various definitions of coefficients in metabolic control analysis are examined
      with respect to their theoretical consistency and practical applicability. We
      suggest agreement upon a definition for control coefficients which is clearly
      distinct from that for response coefficients, in such a way that the former
      describe inherent properties of the metabolic system while the latter refer to
      the influence of special parameters. Advantages and drawbacks of using normalized
      or non-normalized control coefficients are studied. It is shown that normalized
      control coefficients have the advantage of being invariant to a different
      rescaling of the particular fluxes. We demonstrate that some problems are easier
      to tackle if the consistency of time-independent control coefficients with their
      time-dependent counterparts is taken into account. It is shown that the matrix of
      flux control coefficients is an indempotent matrix. This allows an interpretation
      in terms of the transduction of the effect of parameter perturbations. Several
      aspects of the experimental measurement of control coefficients are discussed,
      with special reference to the different definitions.

PMID- 1391688
TI  - The cell division cycle: a physiologically plausible dynamic model can exhibit
      chaotic solutions.
AB  - A mitotic oscillator with one slowly increasing variable (tau L of the order of
      hours) and one rapidly increasing variable (tau R of the order of minutes)
      modulated by a timer (ultradian clock) gives an auto-oscillating solution: cells
      divide when this relaxation oscillator reaches a critical threshold to initiate a
      rapid phase of the limit cycle. Increasing values of the velocity constant in the
      slow equation give quasi-periodic, chaotic and periodic solutions. Thus dispersed
      and quantized cell cycle times are consequences of a chaotic trajectory and have
      a purely deterministic basis. This model of the dispersion of cell cycle times
      contrasts with many previous ones in which cell cycle variability is a
      consequence of stochastic properties inherent in a sequence of many thousands of
      reactions or the random nature of a key transition step.

PMID- 1391689
TI  - Effects of afterhyperpolarization on neuronal firing.
AB  - Stein's model for a neuron is studied. This model is modified to take into
      account the effects of afterhyperpolarization on the neuronal firing. The
      relative refractory phase, following the absolute one, is modelled by a time
      increasing amplitude of postsynaptic potentials and it is also incorporated into
      the model. Besides the simulation of the model, some theoretical results and
      approximation methods are derived. Afterhyperpolarization tends to preserve the
      linearity of the frequency transfer characteristic and it has a limited effect on
      the moments of the interspike intervals in general. The main effects are seen at
      high firing rates and in the removal of short intervals in the interspike
      interval histogram.

PMID- 1391690
TI  - Biodiversity: molecular biological domains, symbiosis and kingdom origins.
AB  - The number of extant species of organisms is estimated to be from fewer than 3 to
      more than 30 x 10(6) (May, 1992). Molecular biology, comparative genetics and
      ultrastructural analyses provide new insights into evolutionary relationships
      between these species, including increasingly precise ideas of how species and
      higher taxa have evolved from common ancestors. Accumulation of random mutations
      and large macromolecular sequence change in all organisms since the Proterozoic
      Eon has been importantly supplemented by acquisition of inherited genomes
      ('symbiogenesis'). Karyotypic alterations (polyploidization and karyotypic
      fissioning) have been added to these other mechanisms of species origin in plants
      and animals during the Phanerozoic Eon. The new evolution concepts (coupled with
      current rapid rates of species extinction and ignorance of the extent of
      biodiversity) prompted this analysis of the field of systematic biology and its
      role in the reorganization of extant species into higher taxa. Two superkingdoms
      (= Domains: Prokaryotae and Eukaryotae) and five kingdoms (Monera = Procaryotae
      or Bacteria; Protoctista: algae, amoebae, ciliates, foraminifera, oomycetes,
      slime molds, etc.; Mychota: 'true' fungi; Plantae: one phylum (division) of
      bryophytes and nine phyla of tracheophytes; and Animalia) are recognized. Two
      subkingdoms comprise the monera: the great diverse lineages are Archaebacteria
      and Eubacteria. The criteria for classification using molecular, ultrastructural
      and genetic data for this scheme are mentioned. For the first time since the
      nineteenth century, logical, technical definitions for each group are given with
      their time of appearance as inferred from the fossil record in the primary
      scientific literature. This classification scheme, which most closely reflects
      the evolutionary history, molecular biology, genetics and ultrastructure of
      extant life, requires changes in social organization of biologists, many of whom
      as botanists and zoologists, still behave as if there were only two important
      kingdoms (plants and animals).

PMID- 1391691
TI  - Phylogenetic consequences of symbioses: Eukarya and Eubacteria are not
      monophyletic taxa.
AB  - In the past systematists have not been concerned with distinguishing the
      different phylogenetic histories for symbiont taxa that have merged within a
      composite taxon, or holobiont. I suggest that symbionts can retain their status
      as discrete taxa and that their independent histories can be included in
      phylogenetic analyses intending to discover monophyletic groups. Use of
      reticulate branches to include independent histories for different symbionts,
      incorporates our improving understanding of evolution and provides greater
      accuracy in denoting monophyletic groups. In an expanded view, a monophyletic
      group includes only and all the descendants of the merged-symbionts' common
      ancestor. Holobiont taxa will have constituent symbionts included in different
      monophyletic groups and there will be a reduction in the number of monophyletic
      groups recognized, particularly at higher taxonomic levels. As a consequence of
      considering symbioses in phylogenetic analyses, the proposed taxa Eubacteria and
      Eukarya are seen to be non-monophyletic, and, thus, poor indicators of
      evolutionary history.

PMID- 1391692
TI  - DMBA-induced intestinal tumors in the Japanese house musk shrew, Suncus murinus
      (Insectivora).
AB  - Intestinal tumors were induced in the Japanese house musk shrew, Suncus murinus
      (Family: Soricidae, Order: Insectivora) with 7,12-dimethylbenz(a)anthracene
      (DMBA). The animals were divided into 10 groups: groups 1-4 received gastric
      intubation of DMBA, groups 5-8 received intraperitoneal (i.p.) injections of this
      agent, and groups 9 (female) and 10 (male) were untreated and served as controls.
      Group 1 (females) and group 2 (males) received 10 mg DMBA at 50 days of age;
      group 3 (females) and group 4 (males) received 2 x 10 mg doses at 50 and 55 days
      of age; groups 5 and 6 (females) received weekly i.p. administration of 1.25 mg
      (group 5) and 2.5 mg (group 6) for 4 weeks; and groups 7 and 8 (females) received
      weekly i.p. administration of 1.25 mg (group 7) and 2.5 mg (group 8) for 8 weeks
      from 8 weeks of age. Intestinal tumors developed in 3/8 (38%) animals in group 1,
      2/6 (33%) in group 2, 5/11 (45%) in group 3, 5/10 (50%) in group 4, 3/6 (50%) in
      group 5, 2/4 (50%) in group 6, 5/8 (63%) in group 7, and 5/6 (83%) in group 8,
      but not in untreated shrews up to 50 weeks of age. The induced tumors, which
      began to appear by 15 weeks after the initial treatment, were randomly
      distributed throughout the intestine. Histologically, the lesions were classified
      as adenocarcinomas similar to those found in humans. BrdU immunohistochemistry
      indicated an extension of the proliferative zone and labeling of many neoplastic
      cells. Local invasion was seen but no metastasis was observed.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1391693
TI  - Effects of postpubertal treatment with progesterone on protein expression in the
      vagina and uterus of mice exposed neonatally to diethylstilbestrol.
AB  - Postpubertal progesterone injections slightly inhibited the proliferation and
      cornification of the vaginal epithelium induced by neonatal injections of
      diethylstilbestrol (DES). In vaginae of neonatally DES-exposed mice (DES mice), 9
      protein expressions (PEX) appeared newly; 13 PEX decreased; 5 PEX increased
      compared to those in the controls. In vaginae of DES mice, PEX were altered by
      postpubertal injections of progesterone (DES-P); 3 PEX disappeared; 11 PEX were
      reversed to those in the controls. Progesterone injections impaired the
      proliferation of the vaginal epithelium, reversing 11 PEX compared to those in
      DES mice. In uteri of DES-P mice, 3 PEX increased, 2 PEX decreased, 2 PEX
      appeared and 1 PEX disappeared compared to those in DES mice. In conclusion, it
      was shown that postpubertal injections of progesterone alter the protein
      expression in the vagina and uterus of DES mice.

PMID- 1391694
TI  - Effects of postpubertal treatment with diethylstilbestrol and tamoxifen on
      protein expression in the vagina and uterus of neonatally diethylstilbestrol
      exposed mice.
AB  - Postpubertal injections of a synthetic estrogen, diethylstilbestrol (-DES), and
      an anti-estrogen, tamoxifen (-Tx), stimulate proliferation of vaginal and uterine
      epithelial cells of ovariectomized (OVX) adult mice. In vaginae of two groups of
      OVX mice treated neonatally with DES (DES-) and oil vehicle alone (Oil-),
      postpubertal injections of DES altered all and 25 out of 37 protein expressions
      examined, except for keratin polypeptides, respectively. Twenty-one of the DES-
      and Tx-altered protein expressions showed the same behavior, suggesting that Tx
      acts as an estrogen agonist on these proteins. Both neonatally Oil- and DES
      treated OVX mice given postpubertal injections of DES (Oil-DES and DES-DES) and
      Tx (Oil-Tx and DES-Tx) showed similar histological changes in the vagina.
      Epithelial proliferation and superficial cornification were observed in vaginae
      of five groups of Oil-DES, Oil-Tx, DES-DES, DES-Tx and DES-Oil (given oil
      postpubertally) OVX mice. In these groups, 13 proteins showed the same behavior,
      implying that these proteins are related to proliferation and cornification of
      mouse vagina. The histology of the uterus in DES-Oil OVX mice closely resembled
      that in Oil-Oil OVX mice; in protein expressions of the uterus, 5 proteins in DES
      DES and 7 proteins in DES-Tx OVX mice were different from those in Oil-DES and
      Oil-Tx OVX mice, respectively. These findings indicate that neonatal DES
      treatment alters the behavior of the vagina and uterus in response to
      postpubertally administered DES and Tx.

PMID- 1391695
TI  - Inhibitory effects of biochanin A on benzo(a)pyrene induced carcinogenesis in
      mice.
AB  - Biochanin A was studied for its capacity to inhibit benzo(a)pyrene (BP) induced
      neoplasia in female Swiss Webster mice. To investigate the effect of biochanin A
      on the initiation step, biochanin A (500 mg/kg) was administered orally 48 hours
      prior to BP (3 mg/mouse), which was also given orally. This sequence of biochanin
      A and BP administration was repeated once a week for a total of 4 weeks. At 26
      weeks after the last treatment, all the mice were sacrificed. To investigate the
      effect of biochanin A on the promotion step, a single subcutaneous injection of
      0.5 mg of BP was given within 24 hours after birth, and biochanin A (0.125
      mg/mouse) was injected intraperitoneally 3 times a week for 6 weeks after
      weaning. In the initiation protocol, the concomitant administration of biochanin
      A showed significant inhibition of the mean number of lung tumors (P less than
      0.001) and the incidence of carcinoma of the forestomach (P less than 0.02). In
      the promotion protocol, biochanin A significantly inhibited the incidence (P less
      than 0.01) and the multiplicity (P less than 0.001) of pulmonary adenoma,
      compared with the group treated with BP alone. These results suggest that
      biochanin A inhibitory potential in the initiation, as well as in the promotion
      step of BP carcinogenesis in female Swiss-Webster mice.

PMID- 1391696
TI  - 1H-NMR spectroscopy of serum in SHN mice with and without spontaneous mammary
      tumours.
AB  - Proton nuclear magnetic resonance (1H-NMR) spectra of serum were studied before
      and after the appearance of spontaneous mammary tumours in intact and anterior
      pituitary grafted SHN mice. In the sera of non-tumourous animals, the lipid CH2
      and CH3 resonances at 1.31 and 0.88 ppm, possibly the peaks of very low density
      lipoprotein (VLDL), were unclear; however, such resonances were apparently
      observed in the sera of mammary tumour bearing mice. On the contrary, alanine,
      beta-hydroxybutyrate, valine and leucine, which peaked clearly in non-tumourous
      mice, declined greatly in tumourous mice. Livers of tumourous mice were heavier
      than those of non-tumourous animals. Quite similar trends in serum spectra and
      liver weight were observed in mice grafted with two anterior pituitaries. These
      findings indicate that tumour absorption of VLDL increases and other metabolic
      pathways are largely altered in association with mammary tumour progression.
      Prolactin, which is essential for mammary tumour development, had little effect
      on serum spectra of mice either with or without mammary tumours.

PMID- 1391697
TI  - Expression of epidermal growth factor, transforming growth factor-alpha and
      epidermal growth factor receptor in thyroid tumors.
AB  - Immunohistochemical study of epidermal growth factor (EGF), epidermal growth
      factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha)
      expression was performed on paraffin-embedded tissue specimens of 12 follicular
      carcinomas, 15 papillary carcinomas and 15 adenomas of the thyroid gland. The
      tumors were placed in one of the following eight groups, according to the results
      of EGF, TGF-alpha and EGFR expression: group 1: none, group 2: only EGFR, group
      3: EGFR and TGF-alpha, group 4: EGFR and EGF, group 5: TGF-alpha, and EGF, group
      6: all three, group 7: only TFG-alpha and, finally, group 8: only EGF.
      Statistical analysis of the results revealed that the ratio of thyroid carcinomas
      with lymph node metastasis was significantly higher in groups 3 and 6 for
      follicular carcinomas (P less than 0.01) and in groups 4, 5 and 6 for papillary
      carcinomas (P less than 0.01). These results suggest that thyroid carcinomas
      expressing the systems EGF/EGFR, TGF-alpha/EGFR or TGF-alpha/EGF/EGFR display
      pathologic features of more aggressive disease. Furthermore, the synchronous
      expression of EGF, TGF-alpha and EGFR indicates that these carcinomas may
      regulate their growth by an autocrine and/or paracrine mechanism.

PMID- 1391698
TI  - Diagnostic accuracy of ultrasound, computed tomography and endoscopic retrograde
      cholangiopancreatography in the detection of pancreatic cancer in patients with
      jaundice or cholestasis.
AB  - A prospective study of jaundiced and/or cholestatic patients (N = 220) was
      carried out to evaluate the diagnostic accuracy of ultrasound (US), computed
      tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) in the
      detection of pancreatic cancer. Thirty-one patients had the final diagnosis of
      pancreatic cancer and two patients had a cancer of the papilla of Vater. The
      sensitivities of US, CT and ERCP were 60%, 97%, 89% and specificities were 92%,
      92%, 94%, respectively. The differences in sensitivity between US and other
      methods were statistically significant (US vs. CT p less than 0.01, US vs. ERCP p
      less than 0.05). In US studies, most false negative results were caused by
      unsatisfying visualization. On the basis of this study, we recommend CT as a
      diagnostic test of pancreatic cancer, if pancreatic cancer is suspected as a
      cause of jaundice and/or cholestasis.

PMID- 1391699
TI  - Cell proliferation of the normal esophagus of mice harbouring a squamous cell
      neoplasia in the uterine cervix.
AB  - Some human tumors have been found to induce proliferative lesions in the squamous
      epithelium in organs remote from the primary tumor. This phenomenon was explored
      in the present animal model. After a single injection of 3H-thymidine, the
      proportion of DNA synthesizing basal and parabasal esophageal cells as well as
      the pace of intraepithelial cell migration was assessed in 124 C57Bl mice. The
      uterine cervix of 57 animals had been painted topically with 3,4 benzo(a)pyrene
      for 5 months, or with the vehicle acetone (44 animals), while 23 animals remained
      untreated. Groups of animals were killed from 8 hours to 10 days following a
      single pulse labelling. The proportion of DNA synthesizing basal and parabasal
      esophageal cells and of their daughter cells (as deduced by observations at
      various time intervals) was similar in animals harbouring neoplasias of the
      uterine cervix, in those treated with benzo(a)pyrene but having histologically
      normal cervical epithelium, in acetone treated as well as in untreated controls.
      Thus, in the model used herein, we failed to demonstrate increased cell
      proliferation in the esophageal mucosa of animals having a squamous cell
      neoplasia in the uterine cervix. The method appears, however, sensitive enough to
      register ongoing cell proliferation patterns and will be applied to the study of
      other experimentally induced tumors.

PMID- 1391700
TI  - Vascular access: concepts for the 1990s.
AB  - Modern hemodialysis requires repeated reliable access to blood vessels capable of
      providing rapid extracorporeal blood flow. This necessity for reliable access to
      the circulation is the Achilles' heel of modern hemodialysis. Native and
      synthetic arteriovenous fistulas remain the preferred method of maintaining long
      term hemodialysis access. Vascular access dysfunctions (thrombosis and infection)
      are the most common complications encountered in the care of end-stage renal
      disease patients. This article focuses on the mechanisms by which permanent
      vascular access for hemodialysis is obtained and deals with the common
      complications that result. This review will evaluate these common complications
      and outline new methods for improving vascular access patency. New concepts
      focusing on the prospective detection and correction of venous stenoses as well
      as on the prevention of other factors that predispose to access failure are
      explored.

PMID- 1391701
TI  - Modification of the percutaneous approach to peritoneal dialysis catheter
      placement under peritoneoscopic visualization: clinical results in 78 patients.
AB  - The placement of percutaneous peritoneal dialysis catheters under direct
      peritoneoscopic visualization is a relatively new technique for establishing
      peritoneal dialysis access. In this study, in which a modification of the
      Seldinger technique was used to facilitate the placement of the peritoneoscope,
      the experience with 82 consecutive catheterization procedures in 78 patients is
      reported. In 2 (2.4%) of 82 catheterization procedures, we were unable to enter
      the peritoneal cavity but experienced no other complications unique to the
      percutaneous approach. Of the 80 successful catheterization procedures, 76
      represented first-time catheter placement and constituted a population subjected
      to life-table analysis examining catheter survival rates, the time to first
      cutaneous exit site or s.c. tunnel infection, and the time to first episode of
      peritonitis. After a follow-up period of 50.1 patient yr, 11 catheters were lost
      because of catheter dysfunction. Other clinical complications included peritoneal
      fluid leaks at the cutaneous exit site in 11 instances (0.22/patient yr),
      cutaneous exit site infection in 7 instances (0.14/patient yr), s.c. tunnel
      infection in 2 instances (0.04/patient yr), and 34 episodes of peritonitis
      (0.68/patient yr). The results of this study demonstrate that the suggested
      modification of the percutaneous placement of peritoneal dialysis catheters,
      under peritoneoscopic visualization, is a viable method for establishing
      peritoneal access.

PMID- 1391702
TI  - Simultaneous measurements of glomerular filtration rate by two radioisotopic
      methods in patients without renal impairment.
AB  - Isotopic clearance techniques have been widely used to measure GFR but may give
      variable results depending on the level of renal function and the technique used.
      GFR, measured by the technique of plasma disappearance of 99mTc-labeled
      diethylenetriaminopentacetic acid ([99mTc]DTPA) was compared with simultaneously
      obtained urinary clearance of [99mTc]DTPA. GFR was also measured by concurrent 24
      h clearance of creatinine. Forty-six measurements of GFR were obtained in 12
      patients who had no evidence of renal disease. Plasma disappearance was measured
      from three timed plasma samples collected 60 to 180 min after the bolus injection
      of 200 microCi of [99mTc]DTPA and was calculated as the product of the volume of
      distribution (milliliters) at time zero and the clearance rate (per minute) as
      determined by the regression of the monoexponential plot. Urinary clearance was
      measured as the average of 3 1-h urinary clearances collected after a water
      diuresis was established. GFR measured by plasma disappearance was significantly
      greater (P less than 0.001) than GFR measured simultaneously by urinary
      clearance. There was a linear correlation between GFR measured by urinary
      clearance and that measured by plasma clearance (r = 0.994). Plasma clearance
      exceeded urinary clearance by a constant factor of 1.3 over the range studied
      (urinary clearance range, 49 to 94 mL/min/1.73 m2). It was concluded that at
      relatively a normal GFR, the plasma clearance of [99mTc]DTPA consistently
      overestimates the urinary clearance of [99mTc]DTPA.

PMID- 1391703
TI  - Detection of sialic acid on cultured cells by binding of a lectin from Limax
      flavus.

PMID- 1391704
TI  - Increased proximal tubular cell catalytic iron content: a result, not a mediator
      of, hypoxia-reoxygenation injury.

PMID- 1391705
TI  - Regulation of solute and water balance and cell volume in the central nervous
      system.
AB  - The mammalian brain is composed of four distinct fluid compartments: blood,
      cerebral spinal fluid, interstitial fluid surrounding glial cells and neurons,
      and intracellular fluid. Maintenance of the ionic and osmotic composition and
      volume of these fluids is crucial for the normal functioning of the brain. Small
      changes in intracellular or extracellular solute composition can dramatically
      alter neuronal signaling and information processing. Because of the rigid
      confines of the skull and complex brain architecture, changes in total brain
      volume can cause devastating neurological damage. As a result, it is not
      surprising to find that the composition and volume of brain intracellular and
      extracellular fluids are controlled tightly under both normal conditions and in
      various disease states. Osmotic and ionic balance in the central nervous system
      is regulated by solute and water transport across the blood-brain barrier, the
      choroid plexus, and the plasma membrane of glial cells and neurons. Despite its
      clinical and physiological significance, however, little is known about the
      underlying cellular and molecular mechanisms by which the central nervous
      system's osmotic and ionic balance is maintained. In this review, the current
      understanding of osmoregulation in the mammalian brain and its role in various
      disease processes such as hyponatremia, renal failure, and hypernatremia will be
      summarized. A detailed understanding of brain osmoregulatory processes represents
      a fundamental physiological problem and is required for the treatment of numerous
      disease states, particularly those encountered in the practice of nephrology.

PMID- 1391706
TI  - Thrombotic microangiopathy: a case report and review of the literature.
AB  - Thrombotic microangiopathy most likely represents a spectrum of diseases
      consisting of multiple etiologies that has a final common pathway of multiorgan
      microvascular thrombosis. The variable responses to several different modes of
      therapy would suggest that more than one pathogenetic mechanism is involved.
      Untreated, it has been associated with very high morbidity and mortality rates. A
      poor understanding of the basic disease process has prevented specific treatment
      modalities, although early diagnosis and availability of dialysis and blood
      product transfusion services remain crucial. Several modes of therapy have been
      used to date, with plasma exchange being the most effective method studied and
      shown to improve survival. On the basis of current knowledge, this form of
      treatment should be instituted promptly in severe cases. Anecdotal reports of
      recovery with vincristine or IgG alone or with the use of IgG after the apparent
      failure of plasma therapy appear promising and deserve further investigation as
      initial therapeutic measures used in thrombotic microangiopathy. Although the
      majority of patients recover with normal renal function, those with severe
      thrombotic microangiopathy may heal through sclerosis with residual hypertension
      and chronic renal impairment requiring continual medical therapy.

PMID- 1391707
TI  - Diminished acetylcholine-induced vasodilation in renal microvessels of
      cyclosporine-treated rats.
AB  - The mechanisms mediating cyclosporin A (CsA)-induced nephrotoxicity have not been
      established, but damage to endothelial cells by CsA has been proposed as an
      important factor. In the study presented here, whether endothelial cell function
      is impaired in the renal vasculature of CsA-treated rats is investigated. The
      vasodilatory effects of acetylcholine (ACH) on norepinephrine (NE)-induced
      microvascular constriction in isolated perfused hydronephrotic rat kidneys
      pretreated with CsA were therefore examined. Hydronephrosis was established to
      permit direct visualization of renal microvessels. Nephrotoxicity was induced by
      s.c. injection of CsA (60 mg/kg/day for 5 days). NE (0.3 microM)-induced afferent
      arteriolar (AA) constriction was exaggerated in CsA rats as compared with that in
      vehicle (olive oil)-treated control rats. (reduction in diameter of -34 +/- 3
      (SE) versus -26 +/- 2%; P less than 0.05). Similarly, efferent arteriolar (EA)
      constriction by NE in CsA rats exceeded that of controls (-34 +/- 2 versus -22 +/
      3%; P less than 0.01). The vasodilatory responses evoked by ACH were blunted in
      CsA rats. The AA response to ACH in CsA rats was significantly decreased (P less
      than 0.005) at ACH concentrations from 1 nM to 1 microM. Similarly, ACH (1 nM to
      100 nM) induced less EA vasodilation in CsA rats (P less than 0.025). In control
      and CsA rats, the addition of nitro-L-arginine abolished AA and EA vasodilation
      induced by ACH, suggesting that the sustained vasodilatory responses of AA and EA
      to ACH are mainly dependent on nitric oxide synthesis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391708
TI  - Effect of cyclosporine on endothelial albumin leakage in rats.
AB  - Short-term treatment of rats with cyclosporine (cyclosporine A [CsA]; Sandimmune)
      results in a marked reduction in intravascular plasma volume, a factor that might
      contribute to the renal dysfunction associated with this potent
      immunosuppressant. To examine the role of plasma extravasation in CsA-induced
      hypovolemia, intravascular plasma volumes (PV), blood volumes, [125I]albumin
      disappearance, and changes in hematocrit (Hct) were measured in Inactin
      anesthetized rats subjected to minimal surgery. The rats were treated for 3 wk
      with either 25 mg/kg/day of CsA s.c. or vehicle. Plasma creatinine and urea were
      significantly elevated, and magnesium was reduced in the CsA group (N = 6) as
      compared with controls (CON) (N = 6). CsA treatment had no effect on urinary
      protein and albumin excretion. Blood volume was significantly lower in CsA than
      in CON (8.4 +/- 0.5 versus 10.6 +/- 0.3 mL/100 g body wt) as was PV (4.3 +/- 0.2
      versus 5.5 +/- 0.2 mL/100 g body wt). Two hours after injection, plasma
      [125I]albumin concentration had fallen by 41 +/- 4% in CsA versus 23 +/- 5% in
      CON. Because Hct, and, hence PV, was unchanged in both groups during these 2 h,
      these data indicate enhanced endothelial albumin leakage in the CsA group. In two
      additional groups of six rats each, acute volume expansion with fresh whole blood
      (2 mL/100 g body wt) resulted in extravasation of plasma. Hct rose by 8.0 +/-
      0.2% in CsA versus 3.8 +/- 0.2% in CON after 150 min, corresponding to 27 +/- 3
      and 15 +/- 2% decreases in total PV, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391709
TI  - Radiocontrast agents induce endothelin release in vivo and in vitro.
AB  - The intravascular administration of the ionic radiocontrast agent sodium
      iothalamate (2.9 g of iodine/kg body wt) to rats induced an increase in plasma
      concentration of immunoreactive endothelin from 21.3 +/- 1.2 to 36 +/- 3 fmol/mL,
      preceded by a transient rise in the plasma level of atrial natriuretic peptide
      and associated with a fall in RBF. Equi-iodine amounts of the nonionic agents
      ioxaglate and iohexol elicited similar or more marked changes in plasma
      endothelin, but hypertonic solutions of NaCl, mannitol, or glucose did not.
      Comparable levels of endothelin produced by infusions of endothelin-1 induced a
      reduction of up to 29% in RBF. Iothalamate and iohexol stimulated endothelin
      release from cultured bovine endothelial cells, suggesting a direct effect of
      ionic and nonionic agents on vascular endothelium. The data invite speculation
      that under some circumstances endothelin release might play a role in the
      circulatory changes caused by these compounds and in the pathogenesis of
      radiocontrast nephropathy.

PMID- 1391710
TI  - Genetic heterogeneity and differences in glomerular hemodynamics between inbred
      colonies of Munich-Wistar rats.
AB  - DNA fingerprint analysis and renal micropuncture studies were performed in Munich
      Wistar rats purchased from Harlan Industries and Simonsen Laboratories to
      determine whether these rats are genetically heterogeneous and exhibit
      differences in glomerular hemodynamics. RBF and GFR were similar in rats from
      both colonies. Glomerular capillary pressure was lower in rats from the Harlan
      colony (46 +/- 2 mm Hg) than in those from the Simonsen colony (56 +/- 2 mm Hg).
      The low glomerular capillary pressure in the Harlan rats was primarily due to a
      lower postglomerular vascular resistance. The estimated whole-kidney
      ultrafiltration coefficient (Kf) was significantly greater in the rats obtained
      from the Harlan colony than in those obtained from the Simonsen colony (0.12 +/-
      0.03 versus 0.05 +/- 0.01 mL/min/g kidney wt/mm Hg). The DNA fingerprints of the
      Simonsen rats were different from those of the Harlan rats. These results provide
      evidence of physiologic and genetic heterogeneity between commercially available
      inbred strains of Munich-Wistar rats in the United States and suggest that
      comparison of results with Munich-Wistar rats from different sources may be more
      difficult than previously recognized.

PMID- 1391711
TI  - Captopril and tubuloglomerular feedback in remnant kidneys of prehypertensive
      rats.
AB  - The activity and characteristics of tubuloglomerular feedback (TGF) are altered
      subsequent to reductions in renal mass or blockade of the renin-angiotensin
      system. This study assessed the combined effects of renal ablation and captopril
      on TGF. Renal mass was reduced in male Sprague-Dawley rats by the surgical
      removal of 1 1/2 kidneys. At 2 and 8 wk postsurgery, TGF was studied by
      micropuncture before and after the administration of captopril (0.5 mg/kg i.v.)
      Before captopril, TGF in remnant kidneys (NX) was characterized by a higher
      tubular perfusion rate required for a 50% maximal response (TGF turning point) as
      compared with intact kidneys of controls (CNT) at both 2 (NX, 35 +/- 3; CNT, = 19
      +/- 1 nL/min; P less than 0.05) and 8 wk (NX, 54 +/- 5; CNT, 20 +/- 1 nL/min; P
      less than 0.05). Captopril significantly increased the turning point in both
      intact and remnant kidneys at both 2 (NX, 43 +/- 2; CNT, 25 +/- 2 nL/min) and 8
      wk (NX, 61 +/- 5; CNT, 28 +/- 2 nL/min) postsurgery. Captopril also significantly
      reduced the maximal TGF response in both intact and remnant kidneys at 2 (NX from
      13 +/- 3 to 7 +/- 1 mm Hg; CNT from 10 +/- 1 to 5 +/- 1 mm Hg) and 8 wk (NX from
      15 +/- 1 to 9 +/- 2 mm Hg; CNT from 13 +/- 1 to 7 +/- 1 mm Hg).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1391712
TI  - Saccular intracranial aneurysms in autosomal dominant polycystic kidney disease.
AB  - The literature on the association of intracranial aneurysms in autosomal dominant
      polycystic kidney disease (ADPKD) consists mainly of case reports and small
      series of patients. To provide a more-detailed description of this association
      and its frequency, the records of all ADPKD patients with saccular intracranial
      aneurysms, all ADPKD autopsy cases including brain examination, and sex- and age
      matched autopsy cases without ADPKD seen at the Mayo Clinic between 1950 and 1989
      and of all Rochester residents with a diagnosis of subarachnoid hemorrhage or
      ADPKD between 1945 and 1984 were reviewed. The presentation of the 41 patients
      (22 men and 19 women; mean age, 46.4 yr) with this association was subarachnoid
      hemorrhage in 33, transient ischemic attacks in 2, incidental angiographic or
      autopsy finding in 5, and discovery during angiographic screening in 1. Thirty
      one, seven, and three patients harbored one, two, and three aneurysms,
      respectively, arising from the middle cerebral artery (N = 23), anterior
      communicating artery (N = 16), internal carotid artery (N = 11), and vertebral or
      basilar artery (N = 4). A family history of intracranial aneurysm, subarachnoid
      hemorrhage, or intracranial hemorrhage at an early age was present in 22% of the
      patients. Small aneurysms (less than 5 mm) were less likely to have ruptured or
      caused symptoms (P less than 0.04). There was a trend for hypertension to be
      associated with the severity of the subarachnoid hemorrhage. Aneurysmal rupture
      occurred before age 50 in 64% of patients. Of the 89 ADPKD autopsy cases with
      brain examination, 22.5% had intracranial aneurysms.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1391713
TI  - Calcium acetate as a phosphorus binder in hemodialysis patients.
AB  - Much interest is currently centered on the use of calcium acetate as a phosphorus
      binder in patients with renal failure. Therefore, this compound in subjects
      previously stable on calcium carbonate and undergoing high-efficiency
      hemodialysis with a dialysate calcium of 2.5 mEq/L was evaluated. Twenty subjects
      were switched from generic calcium carbonate to a single calcium carbonate
      preparation for a period of 2 months. This was followed by a phase (1 month) in
      which calcium acetate was substituted for calcium carbonate at a dose containing
      half the amount of elemental calcium. Subjects then continued calcium acetate for
      6 months. It was found that calcium acetate allowed comparable control of
      immunoreactive parathyroid hormone, calcium, and phosphorus levels compared with
      calcium carbonate. This occurred with half the amount of elemental calcium
      ingested in the form of calcium acetate (349 +/- 25 versus 699 +/- 75 mmol/day; P
      less than 0.001). With this lower dose, the overall incidence of hypercalcemia
      was the same with each formulation. In the eight subjects concurrently receiving
      i.v. calcitriol, the incidence of hypercalcemia was significantly higher during
      the first month of calcium acetate compared with that in those not receiving this
      compound (P less than 0.05). Of those four subjects receiving the high dose of
      calcitriol (2 micrograms thrice weekly), all required either reduction in the
      dose or discontinuation of the drug. Thus, mineral metabolism could be controlled
      adequately with calcium acetate despite using half as much elemental calcium
      compared with calcium carbonate. This, however, did not result in a lower
      incidence of hypercalcemia, particularly in those receiving i.v. calcitriol.

PMID- 1391714
TI  - How tonicity regulates gene expression.
AB  - The expression of a number of different mammalian genes is directly affected by
      hypertonicity. At present, the list of their products includes aldose reductase,
      heat shock proteins, early response factors, and transporters for betaine,
      inositol, and taurine. Hypertonicity increases the abundance of the mRNAs for all
      of them. Aldose reductase mRNA levels increase because of increased transcription
      with little change in the stability of its mRNA. Transcription of the betaine
      transporter also increases. The mechanisms by which hypertonicity increases the
      transcription of these mammalian genes remain speculative. However, the
      consideration of transcriptional control of betaine transport in bacteria and of
      heat shock proteins in many organisms provides interesting insight into this
      question.

PMID- 1391715
TI  - Phospholipase A2 and signal transduction.
AB  - Phospholipases A2 (PLA2) comprise a family of enzymes that hydrolyze the acyl
      bond at the sn-2 position of phospholipids to generate free fatty acids and
      lysophospholipids. Different forms of PLA2 are involved in digestion,
      inflammation, and intercellular and intracellular signal transduction. The sn-2
      position of phospholipids in mammalian cells is enriched in arachidonic acid, the
      precursor of eicosanoids, which have diverse physiologic and pathophysiologic
      effects on the kidney and other organs. Thus, the regulation of PLA2 activity has
      important implications for kidney function. PLA2 regulation involves: calcium,
      pH, protein kinases, GTP-binding proteins, inhibitory and activating proteins,
      metabolic product inhibition, and transcriptional control. The various roles of
      arachidonic acid and cyclooxygenase, lipoxygenase, and cytochrome P450 mono
      oxygenase products of arachidonic acid metabolism, as intracellular messengers,
      in the regulation of membrane channel activities, intracellular enzyme
      activities, cellular calcium homeostasis, mitogenesis, differentiation, cytokine
      and early response gene expression are discussed.

PMID- 1391717
TI  - In renal transplantation, one size may not fit all.

PMID- 1391716
TI  - Growth hormone and the kidney: a case presentation and review of the literature.
AB  - Hypersomatotropism is accompanied by a significant increase in GFR and RPF. A
      case of a patient with acromegaly and supranormal renal function as measured by
      inulin and p-aminohippurate clearances is reported. The literature regarding the
      effects of growth hormone on renal function is reviewed, and the potential
      mechanisms of action and therapeutic implications of these effects are discussed.

PMID- 1391718
TI  - Effect of erythropoietin on hematocrit and blood pressure in normotensive and
      hypertensive rats.
AB  - Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses
      anemia in uremic patients. Of major concern, however, are blood pressure (BP)
      increases during rHuEPO therapy, observed particularly in persons with a history
      of hypertension. To determine whether preexisting hypertension enhances BP
      increases to rHuEPO, BP responses to 2 wk of rHuEPO or placebo were observed in
      spontaneously hypertensive rats (SHR) and their normotensive genetic controls
      (Wistar-Kyoto [WKY] rats. In addition, the role of endothelial-released nitric
      oxide (NO) in BP alterations caused by rHuEPO through i.v. infusions of
      endothelium-dependent and independent vasoactive agents were indirectly examined.
      At trial completion, rHuEPO elevated hematocrit, hemoglobin, and mean cell volume
      more in SHR than in WKY rats (P less than 0.001). Despite the considerable
      increase in hematocrit, rHuEPO did not alter BP in either strain. An infusion of
      NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, elevated
      BP more in rHuEPO-treated SHR than in identically treated WKY rats (P less than
      0.05). Further, the administration of L-arginine caused a greater decrease in
      blood pressure in SHR than in WKY rats, independent of treatment condition (P
      less than 0.01). Because changes in BP with endothelium-independent agents were
      similar across groups, responses to L-NMMA and L-arginine were specific to the
      endothelium and probably independent of basal BP. Thus, rHuEPO provoked greater
      erythropoiesis in SHR than in WKY rats but did not elevate BP. L-NMMA stimulated
      higher BP in SHR treated with rHuEPO, suggesting a compensatory increase in
      vasodilatory NO synthesis to protect against a hypertensive effect of the drug in
      SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391719
TI  - Effect of dietary potassium chloride in borderline hypertensive rats.
AB  - The borderline hypertensive rat is the first filial offspring of the
      spontaneously hypertensive rat and the Wistar-Kyoto rat. With increased dietary
      sodium chloride intake, the borderline hypertensive rat develops hypertension and
      exaggerated cardiovascular and renal responses to acute environmental stress,
      similar to those observed in the hypertensive spontaneously hypertensive rat
      parent. In other models of sodium chloride-sensitive hypertension with different
      genetic background (Dahl rat), dietary potassium chloride supplementation
      protects against the development of hypertension, increased sympathetic nervous
      system activity, and exaggerated responses to acute environmental stress. This
      investigation sought to determine whether the dietary sodium chloride-induced
      development of both the hypertension and the exaggerated responses to acute
      environmental stress could be reversed or prevented by increased dietary
      potassium chloride intake. Dietary potassium chloride intake was increased with a
      1% potassium chloride drinking solution either after 12 wk of 8% sodium chloride
      intake (reversal) or concomitant with the onset of 12 wk of 8% sodium chloride
      intake (prevention). An increase in dietary potassium chloride intake did not
      reverse or prevent the development of either the hypertension or the exaggerated
      cardiovascular and renal responses to acute environmental stress in borderline
      hypertensive rats fed 8% sodium chloride. It is concluded that the difference in
      genetic background between borderline hypertensive rats and other models of
      sodium chloride-sensitive hypertension is an important determinant of the
      protective effect of dietary potassium chloride supplementation.

PMID- 1391720
TI  - Endothelin in a model of acute ischemic renal dysfunction: modulating action of
      atrial natriuretic factor.
AB  - This study was undertaken to investigate circulating endothelin (ET) and
      associated renal hemodynamics in the acute ischemic renal dysfunction associated
      with suprarenal aortic cross-clamping (ACC) in the presence and absence of
      prostaglandin inhibition in the anesthetized dog. Second, the modulating action
      of exogenous atrial natriuretic factor (ANF) was also investigated. In Group I
      (ACC; N = 6), ACC was performed in the absence of prostaglandin inhibition. No
      change in mean arterial pressure, GFR, RBF, renal vascular resistance, or ET was
      noted 2 h after reperfusion when compared with baseline values. In the presence
      of prostaglandin inhibition with indomethacin (10 mg/kg iv) (Group II, ACC +
      INDO; N = 10), an increase in plasma ET was first noted to be elevated above
      baseline ET in Group I as well as during and 2 h after ACC in association with a
      reduction in GFR, marked renal vasoconstriction, and a sustained increase in
      arterial pressure. To evaluate the role of the kidney in this increase in ET,
      another group (Group III, ACC + INDO + NEPH; N = 6) was investigated in the
      presence of prostaglandin inhibition, and bilateral renal artery clamping was
      performed 30 min before ACC and maintained throughout the protocol to simulate
      nephrectomy. In this group, plasma ET concentrations did not increase during ACC.
      Because ANF may antagonize the renal actions of ET in vivo and may suppress ET
      release in vitro, the action of ANF upon GFR and plasma ET was evaluated in Group
      IV (ACC + INDO + ANF; N = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391721
TI  - Interleukin-1-induced alterations in glomerular proteoglycans: biochemical and
      tissue autoradiographic aspects.
AB  - The effect of interleukin-1 alpha (IL-1) on the synthesis of glomerular basement
      membrane heparan sulfate-proteoglycan (HS-PG) was investigated. An ex vivo
      recirculating organ perfusion system was used. Kidneys were perfused with a
      medium containing (35S) sulfate and IL-1 (0.625 to 6.25 ng/mL). After
      radiolabeling was performed, a small cortical piece was saved for tissue
      autoradiography; the remaining kidney and perfusion medium were used for
      biochemical studies. Renal cortices were dissected out, and glomeruli were
      isolated; the PG were extracted and characterized. With exposure to IL-1 (5
      ng/mL), an approximately twofold increase of the radioactivity in the glomerular
      fraction was noted. The increase was unaffected by indomethacin treatment. By
      Sepharose CL-6B chromatography, a single peak of radioactivity with Kav = 0.25
      (macromolecular form of PG) was observed in the control group. The IL-treated
      group had two peaks of radioactivity with Kav = 0.25 and 0.45: the first peak
      contained PG, and the second peak consisted of free glycosaminoglycan (GAG)
      chains. Elution profiles of hydrolyzed tissue GAG chains were similar. No change
      in the ratio of chondroitin to heparan sulfate was observed. By DEAE-Sephacel
      chromatography, the glomerular PG/GAG of the IL-treated group eluted at a
      relatively lower salt concentration, suggesting a change in the charge density
      characteristics. No differences in the elution profiles of media PG/GAG were
      observed. (35S)methionine labeling of proteins showed no significant increase of
      the total radioincorporation in the IL-treated group. Immunoprecipitation studies
      revealed an approximately 88% increase in the de novo synthesis of PG. Tissue
      autoradiography revealed an approximately twofold increase of (35S) sulfate
      radioactivity over the glomerular mesangium, epithelium, and basement membranes.
      These results indicate that IL-1 enhances the synthesis of the macromolecular
      form of PG and the generation of free chains. Conceivably, such alterations may
      lead to defective macromolecular interactions among various components of the
      glomerular basement membrane and compromise the integrity of the ultrafiltration
      unit of the glomerulus.

PMID- 1391722
TI  - Large glomerular size in Pima Indians: lack of change with diabetic nephropathy.
AB  - The mean glomerular volume, glomerular fraction of cortical volume, and
      percentage of obsolescent glomeruli were calculated in kidney specimens from
      autopsies on 34 Pima Indians, of whom 15 had non-insulin dependent diabetes
      mellitus and kidney disease of diabetes mellitus. These values were compared with
      those of black, white, and non-Pima native American individuals without diabetes
      mellitus. Glomerular volume in the Pima Indians was similar in the diabetic and
      nondiabetic subjects and significantly greater than in the white subjects. Black
      and non-Pima native American individuals had glomerular volumes intermediate
      between white individuals and Pima Indians. The mean glomerular volume was not
      affected by the number of obsolescent glomeruli in diabetic Pima Indians. The
      glomerular volume fraction was greater in the Pimas than in the other groups.
      These data showed that glomerular volume in the Pima Indians was significantly
      greater than that in white subjects. There was no difference between diabetic and
      nondiabetics Pimas, and glomerular size was not correlated with the presence or
      degree of glomerulosclerosis in this population.

PMID- 1391723
TI  - Severe hypercholesterolemia inhibits cyclosporin A efficacy in a dose-dependent
      manner in children with nephrotic syndrome.
AB  - In order to identify possible markers of cyclosporin A (CSA) efficacy, the use of
      CSA (6 mg/kg) in 47 children with refractory nephrotic syndrome was reviewed.
      Response was defined as remission of proteinuria within 2 months. Before CSA
      administration, nonresponders (N = 13) were found to have more proteinuria (6
      versus 3 g/24 h; P less than 0.03) and higher serum creatinine levels (0.9 versus
      0.6 mg/dL; P less than 0.03) compared with responders (N = 34). Also, a markedly
      elevated serum cholesterol level (545 versus 312 mg/dL; P less than 0.001) was
      noted among nonresponders. Logistic regression analysis of all three parameters
      isolated serum cholesterol (P less than 0.01) as the only significant predictor
      of CSA nonresponsiveness. Discriminate analysis identified serum cholesterol to
      predict 97% of responders and 77% of nonresponders (P less than 0.0005) to
      conventional CSA doses. The CSA whole-blood trough HPLC levels were
      subtherapeutic among nonresponders (71 ng/mL) compared with responders (162
      ng/mL) (P less than 0.001). Thus, a high serum cholesterol level may prevent the
      achievement of therapeutic CSA blood levels with conventional doses. On the basis
      of this, seven of the nonresponders were re-treated by titration of the CSA dose
      (10 to 14 mg/kg) with their serum cholesterol level. Their mean highest trough
      CSA level was 286 ng/mL. Five patients responded within 2 months. No elevation in
      serum creatinine or evidence of nephrotoxicity on repeat biopsy was seen after 2
      months of therapy in all seven patients. It was concluded that severe
      hypercholesterolemia in nephrotic syndrome patients necessitates the titration of
      the CSA dose with the serum cholesterol level to achieve remission.

PMID- 1391724
TI  - Congenital nephrotic syndrome: preemptive bilateral nephrectomy and dialysis
      before renal transplantation.
AB  - Congenital nephrotic syndrome (CNS) is a rare and uniformly fatal disease if it
      is not treated. Although renal transplantation has been a successful treatment,
      there remains a high mortality rate during the first year of life before
      transplantation. From 1979 to 1987, four patients with CNS, all of whom died
      before they could undergo renal transplantation were treated. On the basis of
      this clinical experience, early elective bilateral nephrectomy and dialysis for
      infants with CNS were initiated to improve overall outcome. From 1987 to 1989,
      this protocol has been used on four consecutive patients with CNS. In these
      patients, bilateral nephrectomy was performed only after patients suffered a
      serious CNS-related complication that occurred between 4 and 6 months of age.
      Despite nephrectomy and the need for chronic dialysis, all patients grew at
      normal or accelerated rates. By 16 months of age, all patients underwent
      successful renal transplantation.

PMID- 1391725
TI  - Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren's
      syndrome and distal renal tubular acidosis.
AB  - Distal urinary acidification abnormalities may arise from transepithelial voltage
      defects, permeability defects, or proton-secretory defects, but tests to
      determine the cellular mechanisms underlying secretory abnormalities have not
      previously been reported. A patient with Sjogren's syndrome and distal renal
      tubular acidosis due to a secretory defect is described, whose kidney biopsy was
      examined by fluorescent immunocytochemistry with an antibody to the M(r) 31,000
      subunit of the mammalian kidney vacuolar H(+)-ATPase and was compared with normal
      human kidney. Staining with the anti-H(+)-ATPase antibody in normal human kidney
      was detected in the brush border microvilli and subvillar invaginations of the
      proximal tubule and in intercalated cells in the collecting duct. A biopsy sample
      from the patient was devoid of any anti-H+-ATPase staining in the intercalated
      cells. Staining was also absent from the proximal tubule brush border microvilli
      but was present in the subvillar invaginations. Although autoantibodies to normal
      human kidney membrane proteins were detected in the serum by immunoblot analysis,
      no immunocytochemical evidence for anti-intercalated cell autoantibodies was
      observed in the patient's serum. This report demonstrates that the basis for the
      proton secretory defect in some patients with distal renal tubular acidosis is
      likely the absence of H(+)-ATPase in the intercalated cells. It also illustrates
      the potential diagnostic utility of anti-H(+)-ATPase antibodies in the
      classification of distal renal tubular acidoses.

PMID- 1391727
TI  - Hypoechoic lesions in the 'bright liver': a reliable indicator of fatty change. A
      prospective study.
AB  - The accuracy of ultrasonographic diagnosis of hypoechoic focal fatty change in
      the 'bright liver' was evaluated in 40 lesions found in 35 patients followed up
      for a mean period of 37.8 months. Patients with ultrasound and laboratory
      findings suggesting liver cirrhosis were excluded from the study. All patients
      underwent a blind liver biopsy in order to verify the diagnosis of diffuse
      disease suggested by the finding of 'bright liver'. No guided biopsy was
      performed on the focal lesions in order to establish the accuracy of ultrasound
      alone in recognizing focal fatty change. Clinical, haematologic and echographic
      follow-up confirmed the diagnosis in all cases. All histological specimens
      revealed liver steatosis, indicating a 100% sensitivity of ultrasonography in
      identifying non-cirrhotic fatty liver with an accompanying focal change.
      Increased echogenicity and hypoechoic focal changes are reliable indicators of
      fatty infiltration, making ultrasonography an acceptable, non-invasive method for
      the diagnosis of liver steatosis.

PMID- 1391726
TI  - Effects of alpha 1 and beta-adrenergic antagonists and 5-hydroxytryptamine
      receptor antagonist on portal-systemic collateral vascular resistance in
      conscious rats with portal hypertension.
AB  - In order to study the acute effects of pharmacological agents on the vascular
      resistance of portal-systemic collaterals, a model of total portal vein occlusion
      with 100% portal-systemic shunts was developed in the conscious rat. The
      haemodynamic effects of several vaso-active substances were evaluated in this
      model and compared with those obtained after saline administration. Prazosin (0.5
      mg), an alpha 1-adrenergic antagonist, significantly reduced mean arterial
      pressure by 29%, portal pressure from 13.8 +/- 1.0(mean +/- s.e.m.) to 10.1 +/-
      0.4 mmHg and portal tributary blood flow (radioactive microspheres) from 13.6 +/-
      2.1 to 11.7 +/- 1.2 mL/min. It also decreased portal-systemic vascular resistance
      from 95 +/- 16 to 73 +/- 9 dyn s/cm5 x 10(3). Propranolol (4 mg), a beta
      adrenergic antagonist, significantly reduced mean arterial pressure by 12% and
      portal pressure from 15.5 +/- 1.2 to 13.3 +/- 0.9 mmHg while reducing portal
      tributary blood flow from 14.6 +/- 1.5 to 11.0 +/- 1.7 mL/min and increasing
      portal systemic collateral vascular resistance from 88 +/- 7 to 103 +/- 8 dyn
      s/cm5 x 10(3). Ketanserin (0.25 mg/kg), a 5-hydroxytryptamine receptor
      antagonist, reduced portal pressure from 15.8 +/- 1.0 to 13.3 +/- 0.7 mmHg at a
      dose that did not alter mean arterial pressure or portal tributary blood flow. It
      achieved this by reducing portal-systemic collateral vascular resistance from 90
      +/- 14 to 74 +/- 13 dyn s/cm5 x 10(3). Saline had no significant effect on
      systemic and splanchnic haemodynamics. This study shows that ketanserin decreases
      vascular resistance of portal-systemic collaterals while propranolol increases
      it. Thus, it is suggested that collateral vascular resistance is accessible to
      pharmacological manipulation.

PMID- 1391729
TI  - Role of endogenous platelet-activating factor (PAF) in endotoxin-induced portal
      hypertension in rats.
AB  - To determine the role of platelet-activating factor (PAF) in endotoxin-induced
      portal hypertension, we performed continuous recording of both blood pressure
      (BP) and portal venous pressure (PVP) in rats following the administration of
      intravenous PAF (25 ng/kg), intraportal PAF (25 ng/kg), intraportal endotoxin (2
      mg/kg), and intraportal endotoxin (2 mg/kg) for 1 min subsequent to pretreatment
      with a specific PAF-antagonist (CV-6209, 1 mg/kg, i.v.). Basal resting values of
      both BP (102.3 +/- 9.3 mmHg) and PVP (7.7 +/- 1.2 mmHg) fell rapidly after
      intravenous infusion of PAF (BP: 36.7 +/- 5.8 mmHg; PVP: 5.7 +/- 0.8 mmHg) and
      followed by gradual return. Intraportal PAF infusion elicited a rapid but less
      severe depression of BP (57.2 +/- 9.4 mmHg) as compared with intravenous PAF
      infusion, whereas PVP was increased transiently around 4 min after treatment
      (11.0 +/- 5.3 mmHg). A similar degree of PVP elevation (10.7 +/- 2.0 mmHg) was
      observed between 8 and 20 min after intraportal administration of endotoxin.
      Depression of BP was initiated 12 min after endotoxin administration but was not
      severe (76.6 +/- 12.8 mmHg). CV-6209 significantly alleviated the endotoxin
      induced elevation of PVP and completely inhibited the hypotension. These
      observations suggest that: (i) PAF-induced elevation of PVP is a direct response
      of the liver to PAF; and (ii) endogenous PAF plays an important role in the
      endotoxin-induced portal hypertension.

PMID- 1391728
TI  - Mutation of the core region of HBV-DNA and submassive hepatic necrosis in
      patients with anti-HBe-positive chronic hepatitis B.
AB  - Three patients with submassive hepatic necrosis developed acute liver failure
      during the severe reactivation of chronic hepatitis B. The activity of hepatitis
      B virus (HBV) DNA polymerase increased in all three patients immediately before
      the onset of hepatic failure. Liver biopsy specimens obtained before and after
      the episode of submassive hepatic necrosis showed progression to advanced liver
      cirrhosis. The nucleotide sequences of the precore and core regions of HBV-DNA
      were investigated in two of the three patients and in another two patients with
      piecemeal and bridging necrosis. The nucleotide and amino acid sequences of the
      HBV-DNA core region changed after reactivation in the the two patients with
      submassive hepatic necrosis, while the sequences in the other two patients with
      piecemeal necrosis remained unchanged before and after reactivation. These
      results suggest that the antigenicity of the HBV-DNA core region may have been
      changed before and after severe reactivation. Due to mutation at the core region,
      a different type of epitope would be expressed on the hepatocytes after
      submassive hepatic necrosis, which would not be a target for the cytotoxic T
      cell. This was evident by the continuation of the normal serum GPT for 5 and 9
      years, respectively.

PMID- 1391730
TI  - Three-dimensional ultrastructure of normal rat hepatocytes by quick-freezing and
      deep-etching method.
AB  - The three-dimensional ultrastructure of nuclei and cell organelles including
      rough-surfaced endoplasmic reticulum (RER), mitochondria, and cytoskeleton were
      studied in normal rat hepatocytes by the quick-freezing and deep-etching method.
      Peroxisomes and mitochondria were observed as spherical structures with granular
      matrices. Peroxisomes were identified by their size and matrices, which were more
      condensed than those of mitochondria. Ribosomes were identified as granular
      structures and were attached to the surface of endoplasmic reticulum.
      Cytoskeletal filaments were identified by their differences in diameter on the
      replica membranes, as well as in conventional ultrathin sections. Microfilaments
      were mainly localized around the bile canaliculi and adjacent to sinusoids.
      Intermediate filaments were observed around the bile canalicular microfilaments.
      Only a few filaments were observed near the lateral plasma membranes. Cross
      bridges measuring 5-7 nm in diameter were localized between the lamellae of RER
      and the surface of mitochondria. The quick-freezing and deep-etching method could
      be used to clarify the three-dimensional association between the cytoskeleton and
      membrane-bound organelles in hepatocytes.

PMID- 1391731
TI  - Effect of naloxone on the haemodynamics and the outcome of experimental acute
      pancreatitis in dogs.
AB  - Endogenous opioid peptides may play a role in the genesis of pancreatic damage in
      acute pancreatitis. The effects of naloxone on the haemodynamic changes in acute
      pancreatitis were investigated by inducing it in dogs with pancreatic ductal
      injection of fresh trypsin-bile mixture. In the control group (n = 8), acute
      pancreatitis was characterized haemodynamically by falls in the maximum positive
      and negative dP/dt (+/- dP/dt), cardiac output (CO) and cardiac index (CI), and
      increases in the pulmonary vascular resistance (PVR) and systemic vascular
      resistance (SVR) as well as an early reduction of pancreatic blood flow (PBF). In
      another set of eight dogs (naloxone group), naloxone was given intravenously 10
      min after the induction of acute pancreatitis (80 micrograms/kg as a bolus + 80
      micrograms/kg/h for 3 h). Compared with untreated dogs, naloxone significantly
      increased PBF and the +/- dP/dtmax; prevented the significant decreases in CO and
      CI and increases in PVR and SVR, and reduced significantly the severity of
      pancreatitis, as assessed by both the histological staging and the mortality
      rate. These results suggest that naloxone limits the progression of acute
      pancreatitis from oedematous to haemorrhagic form. It is proposed that endogenous
      opioid peptides may play a role in the pathophysiology of acute pancreatitis.

PMID- 1391732
TI  - Perforated peptic ulcer in Hong Kong and New South Wales.
AB  - Direct comparisons of ulcer perforation rates and trends between countries have
      not been made in the past. Data on hospital admissions for perforated peptic
      ulcer during 1 January 1979 to 31 December 1985 were collected in Hong Kong (5868
      perforations) and New South Wales, Australia (1669 perforations). Age and sex
      specific rates per 100,000 population were calculated. In Hong Kong, annual
      duodenal ulcer and gastric ulcer perforation rates were 13-16 and under two per
      100,000 population respectively. In New South Wales, the corresponding rates were
      between three and four and under two per 100,000 population, respectively. The
      male:female ratios for duodenal ulcer perforation were consistently about 5:1 in
      Hong Kong and 2:1 in New South Wales, and for gastric ulcer perforation about 2:1
      and 1:1, respectively. The incidence of perforation increased with age, and there
      was a statistically significant rise, over time, in duodenal but not gastric
      ulcer perforation rates in persons aged over 60 years in New South Wales; similar
      trends were seen in Hong Kong. Thus duodenal ulcer perforation occurs five times
      more commonly in Hong Kong than in New South Wales and this is largely
      accountable for by the higher rates of duodenal ulcer perforation in Chinese than
      in Australian males. Such geographical differences can best be explained by the
      occurrence of multiple aetiological mechanisms in ulcer perforation. Furthermore,
      there appears to be an increased susceptibility and an appreciable rising trend
      for duodenal ulcer perforation to occur in the elderly.

PMID- 1391733
TI  - Correlation between CA19-9 production in vitro and histological grades of
      differentiation in vivo in clones isolated from a human pancreatic cancer cell
      line (SUIT-2).
AB  - The production of carcino-embryonic antigen (CEA) and carbohydrate antigen 19-9
      (CA19-9) were investigated in 28 clones isolated from a human pancreatic cancer
      cell line (SUIT-2) and related to in vitro morphology of the clones and in vivo
      tumorigenicity. Clones of fusiform and polygonal cells could be morphologically
      distinguished in confluent cultures. There was no significant difference in CEA
      production between fusiform-cell clones (2.10 +/- 2.70 ng/L x 10(6) per 24 h) and
      polygonal-cell clones (6.01 +/- 7.30 ng/L x 10(6) per 24 h), but polygonal-cell
      clones had higher production of CA19-9 (1176.1 +/- 1628.4 U/L x 10(6) per 24 h)
      than fusiform (6.0 +/- 7.3 U/L x 10(6) per 24 h; P < 0.01). Production of CA19-9
      in vitro correlated with the histological grade of differentiation in vivo in
      nude mice (r = 0.73, P < 0.001), but CEA production did not. The polygonal-cell
      clones developed well-differentiated carcinomas in vivo and produced
      significantly more CA19-9 (P < 0.001) than fusiform-cell clones, which generally
      developed into poorly differentiated tubular adenocarcinomas in vivo. This cell
      line may provide an appropriate system for further studies of the biology and
      therapy of pancreatic cancer.

PMID- 1391734
TI  - Long-term follow-up of dilatation treatment of oesophageal strictures.
AB  - A review of the endoscopy records of 100 consecutive patients with oesophageal
      strictures was undertaken to determine the effectiveness of endoscopic dilatation
      therapy. The follow-up period from presentation ranged from 6 to 72 (mean 39
      months) and the symptom-free period after the last dilatation ranged from 3 to 66
      months (mean 29 months). Three hundred and fifty procedures were performed with
      no perforations and minimal morbidity. Eighty-one patients who had been followed
      for at least 12 months since their last dilatation were free of significant
      dysphagia. Of these 81 patients, 77% became symptom-free within 1 year, and 88%
      within 2 years. Only 35 patients required more than three dilatations; 30
      patients required one dilatation and 35 required two to three dilatations. Age,
      sex, the presence of Barrett's oesophagus, or the oesophageal lumen diameter at
      presentation was not significantly correlated with outcome.

PMID- 1391735
TI  - Primary hypertrophic pyloric stenosis in the adult.
AB  - A case is reported of a 55 year old male patient with primary hypertrophic
      pyloric stenosis who was subjected to distal gastrectomy. Adult hypertrophic
      pyloric stenosis is an uncommon condition which is usually misdiagnosed as
      carcinoma of the antrum. It is a benign disease resulting from hypertrophy of the
      circular fibres of the pyloric canal and is recognizable radiologically by
      narrowing and elongation of the pyloric canal and endoscopically by appearances
      resembling those of the cervix. This condition is probably congenital although
      aetiology has not been established. In the absence of symptoms, no clinical
      treatment is required. However, surgical intervention is advocated, when stenosis
      gives rise to symptoms, there is a suspicion of malignancy, or the ulceration due
      to the disease. Distal gastrectomy with gastroduodenostomy is the treatment of
      choice.

PMID- 1391736
TI  - Treatment of peptic ulcer disease with furazolidone.
AB  - Furazolidone (FZ) has been used in China as a treatment of peptic ulcer disease
      for about 20 years. Clinical and experimental studies suggest that it has good
      short-term and long-term effects on both human and animal ulcers. The ulcer
      healing rate is related to the dosage and course of treatment. The healing rate
      of a high dose, 2 week course is about 70-75% and the relapse rate after 3 years
      is 9.5%. The adverse reactions to FZ are not severe, and are well tolerated in
      most patients. However the mutagenic studies of several biological systems
      indicate that it has a mutagenic effect, but the mutagenic and carcinogenic
      effects on humans and animals remain questionable, because FZ has been
      biotransformed into other metabolites. The mechanisms of FZ in the treatment of
      peptic ulcer disease are not fully understood, perhaps partly due to the
      monoamine oxidase (MAO) inhibitory reaction and partly to the antibacterial
      activity to Helicobacter pylori (HP). The long-term effects of FZ are still not
      clear.

PMID- 1391737
TI  - Advances in hepatitis C: sero-epidemiology and natural history.

PMID- 1391738
TI  - Protective effect of SR 27417, a novel PAF antagonist, on PAF- or endotoxin
      induced hypotension in the rat and the guinea-pig.
AB  - SR 27417, the first member of a newly-developed PAF antagonist series, inhibited
      in a dose-dependent manner the hypotensive effect of PAF in rats. It protected
      rats with an ED50 = 6 micrograms/kg, when given i.v., 1 min before PAF or p.o.
      (ED50 = 170 micrograms/kg) 1 h before PAF administration. After i.v. or oral
      administration, SR 27417 (1 and 3 mg/kg, respectively) exhibited extended
      duration of action (between 48 and 72 h). Similarly, i.v. administration of 1 to
      6 mg/kg of SR 27417 afforded complete protection of guinea-pigs against endotoxin
      induced hypotension but also totally reversed established endotoxin-induced
      hypotension. These results therefore confirm that PAF plays a major role in
      septic shock and that SR 27417 may be an effective prophylactic as well as a
      potent curative drug.

PMID- 1391739
TI  - Production and characterization of antibodies to platelet-activating factor.
AB  - Antibodies directed against platelet-activating factor (PAF) have been raised in
      rabbits immunized with a novel platelet-activating factor analogue-conjugate. An
      analogue of PAF with a carbon double bond at the terminal end of the alkyl chain
      was subjected to ozonolysis and converted to the aldehyde. The aldehyde was
      coupled to thyroglobulin by reductive alkylation and rabbits were immunized via
      either intramuscular or intradermal routes in complete Freund's adjuvant. The
      antibodies are specific for PAF with a preference for the optically active (R)
      enantiomer. There appears to be a requirement for antibody binding of an alkyl
      chain of up to 18 Carbon atoms at C1, and an acetyl group in the C2 position. The
      ability of a number of structural analogues to inhibit binding of tracer to the
      antibody is related to the biological activity of the analogue, and therefore may
      reflect the structural domains that are critical for PAF to interact with its
      receptor.

PMID- 1391740
TI  - Binding of platelet-activating factor to oviductal membranes during early
      pregnancy in the rabbit.
AB  - The present study explores the ability of rabbit oviductal membranes to bind
      tritiated platelet-activating factor [3H]PAF on days 3 and 6 of pregnancy. Under
      optimal conditions (25 degrees C, 120 min) equilibrium saturation analysis
      revealed only one class of binding sites, characterized by Kd s(nM), 80.03 +/-
      11.60 and 11.17 +/- 7.09 and Bmaxs, (pmol/mg protein), 5.25 +/- 2.23 and 1.08 +/-
      0.22 (N = 3, mean +/- SEM) for ampullar membranes on days 3 and 6, respectively.
      The corresponding values for isthmic membranes were Kds, 86.56 +/- 12.01 and
      52.43 +/- 30.49 and Bmaxs, 9.41 +/- 0.67 and 2.88 +/- 1.96 for days 3 and 6,
      respectively. Significant differences between days 3 and 6 were observed only in
      the binding affinities for the ampullar membranes and the binding capacities for
      the isthmic binding sites. [3H]PAF binding was inhibited in the following order
      of decreasing potency: lyso-PAF greater than PAF C18:0 greater than U66985
      greater than PAF C16:0 for day 3 ampullar membranes; and lyso-PAF C16:0 greater
      than PAF C18:0 greater than U66985 greater than PAF C16:0 for day 6 ampullar
      membranes. These studies show the existence of specific oviductal membrane PAF
      binding sites, the binding parameters of which may be related to the stage of
      pregnancy, rather than to the spatial location along the oviduct. The relative
      proportion of endosalpinx to myosalpinx between the ampulla and isthmus may have
      masked inherent differences and account for the relatively low affinity binding.
      The physiological significance of oviductal membrane PAF binding is yet to be
      established.

PMID- 1391741
TI  - Design and validation of a critical care simulation model.
AB  - The high costs of building, equipping, and staffing critical care beds, coupled
      with more restrictive reimbursement policies, are forcing hospital administrators
      to seek ways for determining accurately the number of critical care beds needed.
      Existing critical care bedsizing models do not capture the complexity of today's
      critical care environment, nor have they been formally validated using actual
      hospital performance data. The study described herein was designed to address
      these needs. A GPSS/H simulation model was developed and validated, and includes
      the flow of patients through the study hospital's operating rooms, post
      anesthesia recovery unit, three intensive care units, and two intermediate care
      (stepdown) units.

PMID- 1391742
TI  - Assessing the impact of patient care policies using simulation analysis.
AB  - Simulation models are ideal for assessing the performance of strategic, tactical,
      and operational policies for hospitals. Simulation can validate a proposed
      policy, uncover fallacies of a proposal, or determine the sensitivity of the
      response to a policy change. A simulation model was developed to analyze the
      complex interactions comprising patient placement processes, beginning with
      patient arrivals and continuing through discharge. The model reflects current and
      potential patient assignment policies at a major southeastern general hospital.
      The system developed was utilized to assess proposed policies for the hospital.
      The simulated results of the hospital policy proposals, as well as other
      proposals, demonstrate the usefulness of simulation analysis in hospital policy
      decision-making.

PMID- 1391743
TI  - ASTERIKS--a management game for hospitals.
AB  - ASTERIKS is a PC-based management game dealing with scheduling and sequencing
      operations in hospital departments. The game uses a process-oriented approach for
      simulation. The purpose of the game is to support training of hospital staff in
      this field as a necessary prerequisite for economic efficiency and for patient
      and staff satisfaction. The players have to first define their goals. During the
      game the teams can lay down operational routines in their hospitals, change their
      appointment systems and make staff and investment decisions. ASTERIKS'
      interactive design allows for immediate feedback to the players once the planning
      and simulation phases have been finished. Results include patients and staff
      satisfaction, treatment quality, utilization of resources and the length of stay.

PMID- 1391744
TI  - RURALSIM: the design and implementation of a rural EMS simulator.
AB  - Why were these applications of simulation technology unsuccessful? Parochialism,
      the volunteer nature of EMS planning, and limited regional commitment to resolve
      such complex problems at the local level all combined to present significant
      barriers to implementation. Political factors which posed the most significant
      barriers included: conservative attitudes concerning the funding and regulation
      of EMS activities by local governments; general opposition to governmental
      intervention in the private sector; strong resistance to mandatory standards for
      EMS; jurisdictional disputes between EMS-related agencies; lack of cooperation
      between the local governments; competition between prehospital-care providers and
      between hospitals; overemphasis on local jurisdictional boundaries in the
      planning and delivery of services; and the allocation of EMS resources, such as
      ambulances, according to political priorities, rather than more objective
      criteria. Based upon the results of the four field tests, the following
      observations are relevant: 1. RURALSIM is a very complex simulator. While every
      effort was made to assure generalizability, for any given situation, it required
      extensive modification and tailoring. The result was a model capable of handling
      a rather diverse set of situations, but one that could not be turned over to the
      general public for use. To implement RURALSIM required the participation of the
      University of Pittsburgh research team. The newer simulation languages now
      available alleviate this problem somewhat. 2. RURALSIM's complexity was needed to
      examine the different alternatives proposed by local planners. It was
      particularly needed in order to simulate each region's existing system. Such
      "base-line" simulations were required in order to achieve face validity and
      provide a basis for comparing alternatives. 3. With hindsight, a major weakness
      was the limited amount of face-to-face interaction between local planners and
      decision makers and the University of Pittsburgh staff. Only two trips to the
      region were budgeted. This proved to be insufficient and placed too much
      responsibility for model interpretation and analysis on the local contractors. 4.
      In none of the four test sites did the contractors and/or local health planners
      have the authority, influence and/or incentives necessary to develop regional EMS
      systems. In particular, none of the contractors were in the position to be
      decision makers, nor was there ever only one decision maker. This is not a
      criticism of the contractors, who did their best under difficult circumstances.
      Rather, it is a criticism of the state of eMS system development in the US in the
      early 1980s. There were few examples where regional systems developed
      successfully in the face of serious opposition from local interests.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1391745
TI  - An introduction to patient flow simulation for health-care managers.
AB  - Simulation of patient flow is a remarkably useful management tool. With today's
      software for personal computers, simulation is no longer just for academics and
      consultants. Senior and mid-level managers should actively seek out simulation as
      a problem-solving technique. This article provides health-care managers with the
      fundamental knowledge needed to individually initiate simulation studies of their
      departments.

PMID- 1391746
TI  - A cost-accounting system used in a hospital-related laundry facility.
AB  - A laundry facility supplying linen to several hospitals needs to keep a good
      account of the numbers of different types of linen which enter and leave its
      premises so as to allocate the costs fairly and equitably among member hospitals.
      This task is made difficult by the problem of errors in counting due to high
      volume, different sizes and shapes of linen pieces, and human error in sorting.
      An electronic counting system has been installed in the premises to facilitate
      the process of counting, and this paper describes an approach for correcting the
      counting errors by applying factors that account for the inherent error in the
      system. These factors are estimated from sampling the contents of the sorted
      linen and statistical analysis of the resulting data. An efficient sampling
      scheme is proposed.

PMID- 1391747
TI  - Identification of spinal cord polypeptides related to glial fibrillary acidic
      protein (GFAP).
AB  - Spinal cord cytoskeletal preparations from three different mammalian species
      contain several polypeptides in the SDS-PAGE molecular weight range 100-220 kDa
      which are recognized by all members of a panel of antibodies to glial fibrillary
      acidic protein (GFAP) and by anti-IFA, a panspecific intermediate filament
      protein antibody. The polypeptides are not recognized by antibodies to other
      intermediate filament proteins or to ubiquitin. The proteins coelute with GFAP in
      ion-exchange chromatography, cosediment with GFAP under filament assembly
      conditions, produce similar chemical digest patterns and have an amino acid
      profile close to that of pure GFAP, all properties expected for covalent GFAP
      multimers. Further experiments provide evidence for the existence of such
      multimeric complexes in vivo.

PMID- 1391748
TI  - Induction of c-jun expression in vagal motoneurones following axotomy.
AB  - Using in situ hybridization, we have measured c-jun mRNA expression in the caudal
      medulla oblongata of the rat following sectioning of the cervical vagus nerve.
      Twenty four hours after either unilateral cervical vagotomy or nodose
      ganglionectomy, motoneurones in the ipsilateral dorsal motor nucleus of the vagus
      and nucleus ambiguus expressed increased (2-3 fold) levels of c-jun mRNA. After 7
      days, c-jun mRNA expression was further elevated to levels 8-10-fold higher than
      basal. These results demonstrate an unusual, long-lasting activation of a member
      of the 'leucine zipper' class of immediate early gene, and suggest that immediate
      early genes such as c-jun may be responsible for the regulation of the expression
      of structural protein and neuropeptide genes that have been demonstrated to occur
      following nerve injury.

PMID- 1391749
TI  - Free radicals induce gene expression of NGF and bFGF in rat astrocyte culture.
AB  - Hydrogen peroxide (H2O2) is a type of active oxygen species produced mainly in
      blood by inflammation, ischemia or anoxia. Treatment of rat neonatal cortical
      astrocytes in culture with 0.2-1.0 mM H2O2 which is lethal for hippocampal
      neurons, increases nerve growth factor (NGF) and basic fibroblast growth factor
      (bFGF) mRNA content in a time dependent manner. H2O2 also increases c-fos mRNA
      expression, which is probably involved in the gene regulation of both NGF and
      bFGF. Maximal induction was reached after 6 h of incubation (5.7-fold increase in
      NGF and 2.4-fold induction of bFGF mRNA). Hydrogen peroxide induced bFGF and NGF
      gene expression suggests that neurotrophic factors in astrocytes could be induced
      by lesion, consistent with their protective function in the CNS.

PMID- 1391751
TI  - Persistence of individual dendritic spines in living brain slices.
AB  - A number of theories on the cellular basis of learning and memory propose that
      long-term changes in synaptic strength are encoded by changes in the properties
      of dendritic spines. Such theories imply that individual spines retain their
      identity over time. Using a new technique for fluorescent labelling of synaptic
      structures together with confocal microscopy, we have found that the appearance
      of individual spines on viable cells remains unchanged over observations periods
      of up to 5 hours. Even in slices exposed to kainic acid at concentrations that
      abolished synaptic transmission, groups of spines remained identifiable on cells
      clearly damaged by the toxin. The robust persistence of individual spines
      demonstrated here establishes an essential prerequisite for their potential role
      as mnemonic elements.

PMID- 1391750
TI  - Photochemical stroke and brain-derived neurotrophic factor (BDNF) mRNA
      expression.
AB  - In situ hybridization and Northern blotting were used to study the expression of
      brain-derived neurotrophic factor (BDNF) mRNA in the rat brain following
      photochemical stroke. A focal thrombotic lesion of the sensorimotor cortex was
      produced by intravenously injecting the light-sensitive dye rose bengal and
      exposing the skull to a controlled beam of light. Four hours after the light
      exposure the level of BDNF mRNA was increased in the hippocampus and cortex
      ipsilateral and perifocal to the lesion. The stroke-induced BDNF mRNA increase
      was prevented by the non-competitive glutamate receptor blocker dizocilpine (MK
      801). The results indicate that the activation of N-methyl-D-aspartate (NMDA)
      sensitive glutamate receptors is involved in the stroke-triggered stimulation of
      BDNF mRNA increase.

PMID- 1391752
TI  - The cell adhesion molecule L1 has a specific role in neural cell migration.
AB  - L1-transfected L cells show a markedly enhanced ability for neuronal cell binding
      and promotion of neuron migration compared with control L cells. Further, when
      purified L1 was used as a culture substrate for neurons, it was found to promote
      neuronal adhesion and enhance the speed of migration of cerebellar neurons from
      reaggregated cultures, indicating that it is involved in a determinant step of
      neural cell migration.

PMID- 1391753
TI  - Developmental and lesion induced cell death in the rat ventrobasal complex.
AB  - Naturally occurring and lesion induced neuronal death have been studied in the
      developing rat thalamus. Natural cell death was present from embryonic day (E)19
      until postnatal day (P)8 with a peak occurring at birth. Counts of total neurones
      indicated a postnatal loss of 27%. Unilateral section of the infraorbital nerve
      at birth was associated with increased cell death in the contralateral thalamus;
      this was maximal at P2 and continued until P10. Counts of neurone numbers showed
      a reduction of about 24% of neurones on the contralateral side. A smaller, more
      transient decrease was seen ipsilaterally. The lesion induced cell loss was
      associated with a decrease in volume of the ventrobasal complex, with minimal
      reduction in cell density.

PMID- 1391754
TI  - Barrelfield expansion after neonatal eye removal in mice.
AB  - We investigated the effect of neonatal eye removal on the tangential extent of
      the barrelfield in mice. Areas were measured in drawings made from tangentially
      cut Nisslstained sections of somatosensory cortex. We compared areas of 29
      barrels, corresponding to 29 mystacial vibrissae, between adult mice enucleated
      at birth (n = 13) and their intact littermates (n = 13). Multivariate analysis of
      variance showed that the barrelfield was larger in enucleated mice. This
      expansion was mainly due to the increase in areal extent of the barrels
      corresponding to the dorsalmost row of vibrissae, and of a set of barrels
      corresponding to rostral vibrissae near the nose and mouth. Evidently, early
      enucleation has a significant cross-modal effect on the somatosensory cortex.

PMID- 1391755
TI  - Auditory attention and selective input modulation: a topographical ERP study.
AB  - Event-related potentials (ERPs) were recorded in subjects receiving tones (left
      ear 300 Hz, right ear 6000 Hz) at a rapid rate and trying to detect occasional
      higher-pitched stimuli in a designated ear. ERPs to attended stimuli showed
      enhanced negative amplitudes whose topographical distribution differed from that
      of the exogeneous N1 component. Moreover, the latter was considerably larger for
      low than high tones, whereas the attention effect had similar amplitudes for the
      two tones. Consequently, the attention effect, even when perfectly coinciding in
      time with N1, does not seem to be caused by modulation of the exogeneous N1 but
      rather by a separate process activated by attention. This suggests that attention
      does not modulate initial stimulus representations in audition.

PMID- 1391757
TI  - Change in Fos-like immunoreactivity in the suprachiasmatic nucleus in the adult
      male rat.
AB  - The circadian change in the number of the Fos-like immunoreactive (IR) cells in
      the suprachiasmatic nucleus (SCN) was examined in the adult male rats, whose
      eyeballs were enucleated two months before sacrifice. Their circadian rhythms
      were determined by their locomotor activity. They were sacrificed in the middle
      of the active phase or inactive phase. Then brain sections were cut for
      immunocytochemistry for Fos. A marked increase in the number of the Fos-like IR
      cells was observed in the inactive phase in the SCN, whereas no such increase was
      observed in the supraoptic nucleus. These results indicate that, in the SCN, Fos
      expression was changed with endogenous circadian rhythm in the free-running rat.

PMID- 1391756
TI  - Modification of apomorphine-induced behaviour following chronic swim exercise in
      rats.
AB  - Four week swim exercise schedule (45 min day-1, 6 days each week) in rats led to
      a significant adaptive change in functional responsiveness of dopamine receptors
      (auto-receptors) in the nigrostriatal and mesolimbic system that was evident from
      the modification of behavioural responses elicited by a low dose of apomorphine,
      a direct acting dopamine receptor agonist. Thus, a remarkable increase in yawning
      response, development of full blown stereotypy, as well as profound attenuation
      of locomotory and hypothermic response was observed in exercise-trained rats as
      compared with the non-exercise group (control), following intraperitoneal
      administration of 0.3 mg kg-1 of apomorphine.

PMID- 1391758
TI  - Electrophysiological mapping of body representation in the cortex of the blind
      mole rat.
AB  - The cortex of the blind mole rat (Spalax ehrenbergi) was explored for
      somatosensory responses with special reference to an extension into the occipital
      cortex which serves vision in sighted mammals. Head and body representation was
      similar as in other rodents or mammals. However, the somatosensory area extended
      far into the occipital cortex. No responses to auditory or visual stimulation
      were found caudal to the somatosensory area. However, auditory responses were
      recorded in an area lateral to and slightly caudal to the head representation. It
      is concluded that in this naturally blind animal the area normally occupied by
      the visual cortex serves somatosensory function.

PMID- 1391759
TI  - Brain neurite-stimulating protein promotes formation of mechanosensory endings in
      sensory neuron.
AB  - In the present study we have shown that in the organotypic culture of dorsal root
      ganglia (DRG) of 10-11 day-old chick embryos, the neurite-stimulating protein
      (NSP) from bovine brain promotes the development of branching mechanosensory
      endings. The light and electron microscopic observation revealed that the
      morphological features of these sensory endings are similar to those in vivo. A
      mechanical stimulation of these endings elicited bursts of impulses in the
      sensory neurons.

PMID- 1391760
TI  - The effect of morphine on core and skin temperature in rats.
AB  - The temperature of the tail skin is an important factor determining tail-flick
      latency to noxious radiant heat in rats and mice. The temperature of the skin may
      also be important in determining the behavioural response in the formalin test.
      Morphine in low and moderate doses strongly affected the core and tail skin
      temperatures, preventing the increase in tail skin temperature normally observed
      during testing. For the correct interpretation of the results of several tests of
      nociception, it is important to know how treatment influences the temperature of
      the skin, to be able to correct for this confounding factor.

PMID- 1391761
TI  - Distribution of putative odour receptor proteins in olfactory epithelium.
AB  - To investigate immunohistochemically the spatial localization of putative odour
      receptor proteins, we synthesized a polypeptide which corresponds to a region of
      a putative odour receptor protein, I3, and raised an antibody to the peptide. In
      rat olfactory epithelium, the antibody specifically recognized cilia of a small
      subset of olfactory receptor neurons, suggesting that the odour receptor protein
      is localized selectively in the cilia. Olfactory receptor neurons having
      immunoreactive cilia were distributed sparsely throughout the epithelium. This
      suggests that receptor neurons expressing a similar odour receptor protein are
      probably distributed similarly in the epithelium.

PMID- 1391762
TI  - Perception of timing of movement-onset in a simple reaction time task.
AB  - Subjects judged verbally on temporal order between pressing a switch and a
      marking sound (MS) in a simple reaction time paradigm. They were uncertain when
      sound preceded movement by less than about 60 ms or followed it by less than 130
      ms (transient zone--TZ). The point of subjective equality (defined by 0.5
      probability of correct judgements of temporal order of sound and switching
      onsets) and the median of TZ were shifted about 60 and 35 ms prior movement
      onset, respectively. Estimating mutual timing of movement preparation and
      execution and sensory delays, these shifts correspond to the simultaneity of
      onsets of MS and proprioceptive feedback in the brain. Thus the results suggest
      about proprioceptive origin of perception of active movement onset.

PMID- 1391763
TI  - Voltammetric study of 8-OH-DPAT effect on the raphe-trigeminal 5-HT system.
AB  - The effect of i.p. administration of the selective 5-HT1A agonist 8-hydroxy-2-(di
      N-propylamino) tetralin (8-OH-DPAT) (100 micrograms kg-1) has been investigated
      by in vivo 5-hydroxyindole electrochemical (peak 3) detection in the nucleus
      raphe magnus (NRM) and medullary dorsal horn (MDH) of acute anaesthetized and
      unanaesthetized freely moving rats. 8-OH-DPAT induced a small but significant
      decrease in peak 3 in the NRM and MDH of anaesthetized rats. In freely moving
      animals, a similar small effect was observed at both NRM and MDH levels. With
      reference to similar in vivo studies demonstrating differential responsiveness of
      ascending serotonergic systems to 8-OH-DPAT, it is concluded that the
      serotonergic NRM-dorsal horn system is slightly affected by this 5-HT1A agonist.

PMID- 1391764
TI  - HIV and the brain: evidence of early involvement and progressive damage.
AB  - AIDS is often accompanied by progressive encephalopathy and 'subcortical'
      dementia, but there is uncertainty regarding how early the brain involvement may
      begin in the course of HIV infection. This study used a cognitive auditory
      'oddball' paradigm to elicit sensory and cognitive event related potential (ERP)
      components from healthy controls and from patients at different stages of HIV
      infection. Sensory component latencies did not differ between groups, but
      cognitive components showed progressive delays corresponding to increasingly
      severe clinical stages of HIV infection. The earliest changes were found among
      asymptomatic HIV + patients, suggesting that this test is a sensitive indicator
      of early subclinical CNS damage. In contrast, neither frequency analysis nor
      nonlinear dynamical analysis of the EEG showed differences between healthy
      controls and patients.

PMID- 1391765
TI  - 5,7-DHT facilitated lordosis: effects of 5-HT agonists.
AB  - The role of 5-HT (serotonin) in regulating lordosis was investigated by combining
      peripheral administration of the 5-HT agonists 8-OH-DPAT (8-hydroxy-2-[di-N
      propylamino]tetralin) or TFMPP (1-[m-trifluoromethylphenyl]piperazine), with
      intrahypothalamic application of the 5-HT neurotoxin 5,7-DHT (5,7
      dihydroxytryptamine). The 5-HT1A agonist, 8-OH-DPAT, significantly inhibited
      lordosis in 5,7-DHT-treated and non-treated rats. TFMPP, an agonist at 5-HT1B and
      5-HT1C receptors, significantly facilitated lordosis in 5,7-DHT-treated and non
      treated rats. Our results show that both inhibitory and facilitatory influences
      of hypothalamic 5-HT on lordosis, are modulated via postsynaptic receptors.

PMID- 1391766
TI  - Acyl-(acyl-carrier protein) hydrolase from squash cotyledons specific to long
      chain fatty acids: purification and characterization.
AB  - Acyl-(acyl-carrier-protein) hydrolase (EC 3.1.2.14) releases fatty acids from the
      end-product of fatty acid synthesis in plastids for the subsequent synthesis of
      glycerolipids in the cytoplasm. Isoelectric focusing of chloroplast stroma
      proteins from squash cotyledons suggested that there were at least three isomeric
      forms of acyl-(acyl-carrier-protein) hydrolase having pI values of 4.5, 5.3 and
      7.8. The pI 4.5 and pI 5.3 forms showed maximum activity at pH 9.8 whereas the
      activity of the pI 7.8 form increased within the range 6.2 to 10.2 but no optimum
      was seen. The pI 4.5 form was purified 100,000-fold from squash cotyledons. The
      highly purified fraction contained two polypeptides, whose molecular masses were
      estimated to be 35 kDa and 33 kDa by SDS-PAGE. It is suggested that the 33 kDa
      polypeptide was a degradation product of the 35 kDa polypeptide. Oleoyl-(acyl
      carrier protein) was the preferred substrate of this enzyme over palmitoyl- and
      stearoyl-(acyl-carrier protein), whereas lauroyl-(acyl-carrier protein) was
      nearly inactive. These results indicate the enzyme is specific for long-chain
      acyl-(acyl-carrier protein).

PMID- 1391768
TI  - Cloning and characterization of cDNAs coding for Vicia faba polyphenol oxidase.
AB  - Three cDNA clones were isolated which code for the ubiquitous chloroplast enzyme,
      polyphenol oxidase (PPO), from Vicia faba. Analysis of the cloned DNA reveals
      that PPO is synthesized with an N-terminal extension of 92 amino acid residues,
      presumed to be a transit peptide. The mature protein is predicted to have a
      molecular mass of 58 kDa which is in close agreement to the molecular mass
      estimated for the in vivo protein upon SDS-PAGE. Differences in the DNA sequence
      of two full-length and one partial cDNA clones indicate that PPO is encoded by a
      gene family. Analysis of the deduced amino acid sequence shows that the
      chloroplast PPO shares homology with the 59 kDa PPOs in glandular trichomes of
      solanaceous species. A high degree of sequence conservation was found with the
      copper-binding domains of the 59 kDa tomato PPO as well as hemocyanins and
      tyrosinases from a wide diversity of taxa.

PMID- 1391767
TI  - Multiple ocs-like elements required for efficient transcription of the mannopine
      synthase gene of T-DNA in maize protoplasts.
AB  - Regulatory elements controlling transcriptional activity of the mannopine
      synthase 2' promoter (mas 2') were defined by analysis of deletion mutants in
      transient expression assays in maize protoplasts. Deletion of the region between 
      305 and -290 containing sequence similarity to the octopine synthase (ocs)
      promoter element reduced activity by 67% compared to wild type activity. Less
      than 1% of the activity remained in 5' deletions downstream of -153. Inclusion of
      various heterologous enhancer-like sequences immediately upstream of position 
      325 increased activity by up to 7.5-fold. Insertion of the -325 to -275 sequence
      alone, or in combination with heterologous enhancer-like elements, restored
      activity of some of the 5'-deletion mutants. Restoration of activity was not
      obtained with mutants deleted past position -127. Our results suggest that a
      single class of nuclear proteins from maize interact with high affinity at
      elements designated mas b (-306 to -275; mas 1' element), d (-127 to -108), and e
      (-82 to -39; mas 2' element) as well as the 20 bp element from the ocs promoter.
      Although the binding site at mas d only appears to accommodate a single protein,
      this element has the potential to make a weak, but positive, contribution to the
      activity of the mas 2' promoter. The binding of nuclear proteins could not be
      demonstrated at mas a and c, both of which showed limited homology to the ocs
      element. Mutational evidence suggested that mas a and c may also contribute to
      mas 2' transcription.

PMID- 1391769
TI  - Temporal and spatial regulation of a novel gene in barley embryos.
AB  - The temporal and spatial pattern of expression of a novel barley gene is
      described. The gene has been identified through the differential screening of a
      cDNA library constructed to poly(A)+ RNA of zygotic embryos. Transcripts
      corresponding to the cDNA, pZE40, become abundant in the non-axial tissues of the
      developing embryo within 8-10 days after anthesis, when steady-state levels are
      high in the scutellum, coleoptile and coleorhiza, with the exception of the
      scutellar epithelium. This expression pattern is maintained throughout maturation
      of the embryo until levels eventually decline as the grain desiccates. On
      germination, there is a transient re-appearance of mRNA to pZE40, with
      accumulation specifically restricted to the scutellum of the seedling. In situ
      hybridization has enabled the detection of transcripts elsewhere in the barley
      plant, in highly localized groups of cells. The timing and cell specificity of
      expression suggests the gene product is involved in the synthesis and/or
      transport of metabolites.

PMID- 1391770
TI  - Organization and expression of a phycobiliprotein gene cluster from the
      unicellular red alga Cyanidium caldarium.
AB  - We have sequenced a plastid gene cluster from the unicellular red alga Cyanidium
      caldarium which is located downstream from the psbA gene and contains, in the
      following order, genes for a beta-allophycocyanin-like protein (apcB'), a
      putative 9.5 kDa allophycocyanin linker protein (apcL9.5) and a putative 29 kDa
      phycocyanin linker protein (cpcL29). The apcB' and apcL9.5 genes are organized in
      the form of an operon. The cpcL29 gene is transcribed monocistronically from the
      opposite strand of DNA. Both transcription units are probably terminated at a 25
      bp inverted repeat 3 and 5 bp downstream of the stop codons of the apcL9.5 and
      cpcL29 genes, respectively. The levels of both transcripts are greatly reduced in
      the dark as is the psbA transcript. Downstream from the phycobiliprotein gene
      cluster two open reading frames (ORFs) were found which are homologous to ORFs
      from plastid DNAs and cyanelle DNA of Cyanophora paradoxa. Sequence homologies
      between genes analysed in this study and corresponding genes from cyanobacteria,
      chlorophytic plastids and cyanelles point to a large phylogenetic distance
      between the plastids of Cyanidium and cyanobacteria and other plastid types.

PMID- 1391771
TI  - Cloning and characterization of a pathogen-induced chitinase in Brassica napus.
AB  - A chitinase cDNA clone from rapeseed (Brassica napus L. ssp. oleifera) was
      isolated. The cDNA clone, ChB4, represents a previously purified and
      characterized basic chitinase isozyme. The longest open reading frame in ChB4
      encodes a polypeptide of 268 amino acids. This polypeptide consists of a 24 amino
      acid N-terminal signal peptide, a cysteine-rich domain and a catalytic domain.
      The primary structure of the mature ChB4 shows a low degree of identity with
      class I and II chitinases, 43-48% and 35%, respectively. In contrast, ChB4 shows
      62% identity to a basic sugar-beet chitinase and 63% identity to an acidic
      chitinase from bean. The expression of chitinase messenger RNA (mRNA) in response
      to infection with Phoma lingam (Tode ex. Fr.) Desm. was examined by northern
      hybridization and scintilation counting. A differential induction was seen
      between resistant and susceptible cultivars where 3-fold higher chitinase
      transcript levels were estimated one day after inoculation in resistant as
      compared to susceptible cultivar. This difference diminished eight days after
      inoculation. Southern hybridization analysis indicates that the chitinase is
      encoded by a small family of genes.

PMID- 1391772
TI  - Import and processing of the precursor of the Rieske FeS protein of tobacco
      chloroplasts.
AB  - cDNA clones encoding the precursor of the Rieske FeS protein of tobacco
      chloroplasts have been characterised and shown to derive from two different
      genes. The 5' ends of the corresponding transcripts have been cloned using primer
      extension and PCR. The nucleotide sequences of the cDNAs (and their 5'
      extensions) predict precursors for the tobacco proteins which differ in 4 amino
      acid residues out of a total of 228 residues and show high homology with the pea
      and spinach precursors. The tobacco precursor proteins contain N-terminal
      presequences of 49 amino acid residues which lack 17 amino acid residues present
      at the N-terminus of the spinach presequence. The 26 kDa precursor obtained by
      transcription and translation of one of these cDNAs in vitro was efficiently
      imported and correctly processed to the mature 20 kDa protein by isolated pea or
      tobacco chloroplasts. The precursor was also processed to its mature size by a
      peptidase present in the stroma of chloroplasts.

PMID- 1391773
TI  - Biosynthesis of active spinach-chloroplast thioredoxin f in transformed E. coli.
AB  - The recently cloned gene for spinach chloroplast thioredoxin f was subcloned in a
      modified pKK233-2 expression vector and used for transformation of Escherichia
      coli cells containing the Iq plasmid. After induction with IPTG (isopropyl-beta-D
      thiogalactoside) the transformed cells produce the chloroplast protein in large
      amounts as insoluble deposit within the cell. The protein has been solubilized,
      purified and analysed for activity. It shows no difference in catalytic activity
      from native spinach chloroplast thioredoxin f. Its electrophoretic behaviour
      suggests that the native thioredoxin f may have a different N-terminus than was
      assumed on the basis of the protein sequencing results.

PMID- 1391774
TI  - Isolation and sequence analysis of the genomic DNA fragment encoding an aspartic
      proteinase inhibitor homologue from potato (Solanum tuberosum L.).
AB  - A genomic DNA clone encoding an aspartic proteinase inhibitor of potato was
      isolated from a lambda EMBL3 phage library using the aspartic proteinase
      inhibitor cDNA as a hybridization probe. The gene has all characteristic
      sequences normally found in eucaryotic genes. Typical CAAT and TATA box sequences
      were found in the 5'-upstream region. In this part are also two putative
      regulatory AGGA box sequences located. In the genomic sequence there are no
      intron sequences interrupting the coding region. An open reading frame of the
      gene encodes a precursor protein of 217 amino acids which shows high percent
      identity with the aspartic proteinase inhibitor cDNA.

PMID- 1391775
TI  - Vicilin-like seed storage proteins in the gymnosperm interior spruce (Picea
      glauca/engelmanii).
AB  - A seed storage protein cDNA was characterized from a library of interior spruce
      (Picea glauca/engelmanii complex) cotyledonary stage somatic embryos. The deduced
      amino acid sequence predicts a 448 amino acid (50 kDa) polypeptide with 28-38%
      identity with angiosperm vicilin-like 7S globulins. XXC/G codon usage is low
      (47%) relative to monocot angiosperms while pairwise comparisons show that
      spruce, monocot, and dicot vicilins are approximately equal in amino acid
      divergence. Although small by comparison, the spruce vicilin contains an N
      terminal hydrophilic region characteristic of angiosperm 'large' vicilins.
      Genomic Southern blotting predicts that the cDNA is encoded by a gene family.

PMID- 1391776
TI  - cDNA cloning and gene expression of the major prolamins of rice.
AB  - A full-length cDNA (pS 18) encoding the 16 kDa rice prolamin composed of 158
      amino acids was sequenced. Analysis of N-terminal amino acid sequence of a major
      rice prolamin indicated that an 18 amino acid signal peptide was removed from 16
      kDa precursor prolamin to form the 14 kDa prolamin during seed development.
      Synthesis of the 16 kDa precursor prolamin began around 8 days after flowering
      (DAF), increased remarkably at 8-11 DAF and gradually reached maximum levels with
      the maturation of rice seeds.

PMID- 1391778
TI  - Molecular cloning of the gene encoding developing seed L-asparaginase from
      Lupinus angustifolius.
AB  - A genomic sequence encoding Lupinus angustifolius L-asparaginase has been
      obtained, and is the first report of this gene from a plant source. The 3.2 kb of
      DNA sequenced contains a 1136 bp 5' flanking sequence, four exons and three
      introns. Intron-exon borders were mapped by comparing the genomic sequence with
      that of a L. arboreus cDNA. Primer extension analysis revealed transcription
      start sites 16 bp and 13 bp 5' of the initiating ATG for L. angustifolius and L.
      arboreus, respectively. The 5' flanking region contained sequences associated
      with seed-specific expression.

PMID- 1391777
TI  - Structure and nucleotide sequence of tomato HMG2 encoding 3-hydroxy-3-methyl
      glutaryl coenzyme A reductase.

PMID- 1391779
TI  - Isolation and characterization of a cDNA encoding a 3-hydroxy-3-methylglutaryl
      coenzyme A reductase from Nicotiana sylvestris.
AB  - A cDNA library from freshly isolated mesophyll protoplasts of Nicotiana
      sylvestris was differentially screened using cDNAs from leaves, leaf strips
      submitted to the same stress as protoplasts during the isolation procedure, and
      cell suspension cultures. One of the selected clones (6P2) was found to encode a
      putative polypeptide highly homologous to previously characterized 3-hydroxy-3
      methylglutaryl coenzyme A reductases. The C-terminal region of the polypeptide
      was highly conserved whereas its N-terminal region including the trans-membrane
      domains and the linker was more variable. Apart from protoplasts, the 6P2 gene
      was found to be expressed in apexes, anthers, roots, and in stressed leaf strips
      after 24 h of culture, during the hypersensitive reaction to viral infection and
      after HgCl2 treatment. This pattern of expression is consistent with a role in
      plant defence mechanisms.

PMID- 1391780
TI  - Sequence analysis of three members of the maize polygalacturonase gene family
      expressed during pollen development.

PMID- 1391782
TI  - Sequence comparison of two highly homologous phycoerythrins differing in bilin
      composition.
AB  - Genes encoding the alpha and beta subunits of class II phycoerythrin from
      Synechococcus sp. strain WH8103 were cloned and sequenced. The deduced amino acid
      sequences were compared to class II phycoerythrin from Synechococcus sp. strain
      WH8020 and found to share 92% identity, yet the proteins differ in the bilin
      isomer (phycoerythrobilin versus phycourobilin) bound to two of the six
      chromophore attachment sites. Amino acid residues which might contact the bilin
      at each of the two variable sites were inferred by sequence alignment with
      phycocyanins. Putative bilin-contacting residues differing between the two
      phycoerythrins were identified which may determine bilin specificity.

PMID- 1391781
TI  - Sequence and organization of a 7.2 kb region of wheat mitochondrial DNA
      containing the large subunit (26S) rRNA gene.
AB  - We report the sequence of a 7.2 kilobase pair DNA fragment containing a copy of
      the wheat mitochondrial gene (rrn26) that encodes the mitochondrial large-subunit
      ribosomal RNA (26S rRNA). The mature 26S rRNA was determined by direct RNA
      sequencing to be 3467 nucleotides long, and to share a 5'-terminal
      pentanucleotide (5'-AUCAU), thought to be important in post-transcriptional
      processing, with the wheat mitochondrial small-subunit (18S) rRNA. Two other
      prominent features of the sequence were noted. First, upstream of rrn26 are
      located two tandem copies of a 70 base pair element containing a putative
      mitochondrial promoter motif (TCGTATAAAAA). Second, downstream of rrn26 is a
      sequence element that, if transcribed, would produce an RNA with a secondary
      structure resembling that of tRNAs but differing sufficiently from the latter
      structure to preclude any transcript from functioning normally in translation.
      These upstream and downstream sequence elements may play a role in the expression
      of rrn26 in wheat mitochondria.

PMID- 1391783
TI  - Particle bombardment-mediated transient expression of a Brazil nut methionine
      rich albumin in bean (Phaseolus vulgaris L.).
AB  - Bean (Phaseolus vulgaris L.) mature embryos were transformed using biolistic
      methods with a plasmid containing 2S albumin and beta-glucuronidase structural
      sequences, both under the control of the 35S CaMV promoter. We have shown that
      chimaeric tissues could be obtained and that both structural sequences were
      expressed to similar levels.

PMID- 1391784
TI  - The tomato nia gene promoter functions in fission yeast but not in budding yeast.
AB  - A fragment comprising 1 kb of the 5' region and the 81 first nucleotides of the
      coding region of the tomato nitrate reductase nia gene was placed in
      translational fusion with the lacZ reporter gene. This construct was introduced
      in budding and in fission yeast using a derivative of the Saccharomyces
      cerevisiae/Schizosaccharomyces pombe autonomously replicating vector pUZL. Beta
      galactosidase activity was detected in S. pombe but not in S. cerevisiae. Primer
      extension experiments show that in fission yeast transcripts are initiated at the
      same starting point as in tomato, indicating for the first time that a plant
      promoter can be correctly recognized in fission yeast.

PMID- 1391785
TI  - Seasonal changes in the concentration of the major storage protein and its mRNA
      in xylem ray cells of poplar trees.

PMID- 1391786
TI  - Validation of a patient satisfaction system in the United Kingdom.
AB  - This paper describes the results from a study to assess the validity of a patient
      satisfaction system used extensively in the United Kingdom. The study involved
      over 700 interviews with patients. The face, content, discriminant and construct
      validity have been tested. The discriminant and construct validity were judged to
      be satisfactory and there was some evidence of face validity. The results suggest
      that this system has the ability to reveal differences in satisfaction between
      hospitals. The findings from the study are being used to modify the questionnaire
      design in order to improve the system's ability to indicate which aspects of the
      service require improvement.

PMID- 1391787
TI  - Continuous improvement of nursing practice: experience in Quebec.
AB  - Health care professionals must be accountable for the quality of their practice
      and self-regulating professional organizations have the responsibility to ensure
      that the public receives the best possible care to which it is entitled. Quebec's
      legislation mandates professional corporations to supervise the practice of their
      members. The nursing profession comes under that legislation and, at l'Ordre des
      infirmieres et infirmiers du Quebec, a program of professional inspection has
      existed since 1976. The philosophy of this program is based on individual and
      collective responsibility of nurses towards the continuous improvement of their
      practice and the enhancement of the quality of care they provide. Standards and
      criteria of competence were elaborated with the participation of groups of
      nurses, validated by large samples of the population and distributed to all
      nurses. Evaluation tools were devised and have progressed over the years. The
      concepts of self-evaluation (Bandura, Am Psychol 33: 344, 1978; Bandura, Prentice
      Hall, 1986; Knox and MacKay, Nurs Papers/Perspect Nurs 4: 17, 1982) and of self
      managed collective development (Payette, Rev quebecoise Psychol 5: 104, 1984)
      have inspired the program, allowing nurses to identify their needs, set
      priorities and determine their plan of action. A study to evaluate the impact of
      the program is now in progress. This article will describe the conceptual
      framework, the method of evaluation, its application, the reactions of nurses as
      well as some of the results observed concerning the improvement of practice and
      of quality of care.

PMID- 1391788
TI  - A pilot project on quality assurance in nursing care in the state of Schleswig
      Holstein, Federal Republic of Germany.
AB  - As a direct result of the law passed in Germany requiring the practice of quality
      assurance in health care which has been in effect since 1 January 1989, the
      Institute for Health Systems Research in Kiel piloted a project on quality
      assurance in medicine in 12 hospitals in Schleswig-Holstein from September 1989
      to February 1991. Two procedures for measuring the quality of nursing care were
      also developed in two of these hospitals. These procedures were oral care aided
      by nursing staff and oral care carried out by nursing staff. The pilot project
      was then evaluated by the Institute. An extension of the medical side of the
      project to cover all 80 hospitals in Schleswig-Holstein was planned to begin on 1
      January 1992. As far as the nursing side is concerned, approximately 10
      procedures will be developed and tested in eight hospitals.

PMID- 1391789
TI  - Specifying quality in health and social care.
AB  - Two popular ways of specifying the quality of health and social care are
      explained. Examples are used to illustrate: (a) the mission statement/minimum
      standard method; and (b) the aim/objective method. Strengths and weaknesses of
      these approaches are highlighted by using a writing-style analyser, and an
      evaluation model from the literature. Ways of correcting some of the weaknesses
      are suggested.

PMID- 1391790
TI  - Is blood pressure measurement with a standard cuff reliable?
AB  - This study compares blood pressures measured with a standard cuff (rubber bag 12
      x 35 cm) with concomitantly measured intra-arterial pressures in 48 subjects.
      With the standard cuff, and using a diagnostic cut-off limit for diastolic
      hypertension of 90 mmHg, 15/48 patients were found to be hypertensive, whereas
      only 4/48 had intraarterial pressure above 90 mmHg. Thus, the specificity of the
      non-invasive method was only 75%. If higher diagnostic cut-off limits were used,
      e.g. 95 mmHg, specificity increased to 84%, and with lower cut-offs specificity
      was 63% for 85 mmHg and 52% for 80 mmHg. A specificity of only 75% is very poor
      for a method commonly used in screening examinations and may lead to considerable
      over-diagnosis of mild hypertension.

PMID- 1391791
TI  - Effectiveness of the daily record review at the medical emergency room department
      in a French teaching children's hospital.
AB  - We evaluate the effectiveness of the daily record review (DRR) of 4393 ambulatory
      medical patients seen at the emergency room department of a teaching pediatric
      hospital in Paris between 8th January and 11 March 1991. For these patients, 137
      potential quality problems were found, 117 of them remaining after discussion
      with the junior. For 80 of the 117 confirmed problems (68.4%), the reviewing
      senior estimated that sufficient advice had been given to the child's usual
      caretaker or health care provider and (or) the children returned to seek medical
      advice when indicated. Experts proved the procedure to be reliable: they detected
      a problem for 36% of the cases with potential quality problems and for only 2% of
      a sample of control records considered without potential quality problems after
      the DRR.

PMID- 1391792
TI  - Preoperative evaluation in non-cardiac surgery: cardiac risk assessment.
AB  - Nine hundred and ninety patients, ages 20 years or older, undergoing non-cardiac
      elective surgery were prospectively studied to identify high cardiac risk
      preoperative factors in a case-mix population and to assess cardiological risk.
      The prevalence of major cardiac complications was 2.3%, including 0.8% mortality.
      Univariate analysis showed that: age; history of chest pain; dyspnea;
      hypertension; presence of systolic murmur and third sound; diastolic pressure
      greater than 95 mmHg; electrocardiogram left ventricular hypertrophy;
      cardiothoracic ratio greater than 0.5 and valvular calcifications are associated
      with cardiac complications (p = 0.001-0.02), with low sensitivity (range: 14-38%)
      and high specificity (range: 85-98%). Cardiological referral was required for 169
      patients (17%) that showed a higher prevalence of cardiovascular diseases (85%)
      and of cardiac complications (5.3%). Cardiologists required further tests for 13
      patients (7.7%) and modified therapy for 93 (55%). High cardiac risk patients are
      identified preoperatively in current practice and cardiological referral is
      frequent; further studies are mandatory to evaluate the most effective and
      efficacious procedures.

PMID- 1391793
TI  - Quality of care in residential homes: a comparison between Israel and Florida.
AB  - This paper reports on two studies of the quality of care in long-term care
      institutions for the elderly, one in Israel and one in Florida, which used the
      tracer methodology developed by the JDC-Brookdale Institute of Gerontology for
      examining quality of care in such institutions. A tracer is a well-defined and
      frequently occurring problem which has a known treatment. Tracers from the
      medical, nursing and psychosocial areas of care were used in the studies. Data
      were collected by multidisciplinary teams of medical and paramedical personnel
      who examined and interviewed elderly residents, interviewed staff members,
      conducted observations, and reviewed records. Differences inherent in the two
      study groups--such as in cultural norms and organizational systems--were taken
      into consideration, and the instruments were adjusted accordingly. The tracer
      method proved to be a feasible method for assessing quality of care in both
      locales. Findings regarding 12 tracers show that for units previously assessed as
      either good or poor/mediocre by surveyors, good units consistently scored higher
      than poor/mediocre units in quality of care. Florida scored higher for quality of
      care in the medical area, and Israel in the nursing and psychosocial areas.

PMID- 1391794
TI  - A nationwide quality assurance program can describe standards for the practice of
      pathology and laboratory medicine.
AB  - An important component of quality assessment is the analysis of peer group
      comparisons, although little data are available for evaluation. We developed and
      tested six interinstitutional quality indicators related to Pathology and
      Laboratory Medicine among 36 institutions. Results showed that the mean frequency
      of intraoperative frozen section consultations (6.0%), sensitivity of fine needle
      aspiration cytology diagnosis (87%), nosocomial infections (5.0%) and average
      cross-match to transfusion ratio (2.1%) was comparable with previous studies, but
      the range of values was large. The median stat laboratory turnaround time of
      approximately 1 hr for CSF cell count, glucose, protein and gram smear was
      considerably longer than expected from previous investigations, and was longer
      for larger institutions. Analysis of serious laboratory reporting errors showed
      the lowest number detected by individuals working in transfusion medicine, and
      highest numbers among hematology workers. We conclude that interinstitutional
      comparison of data from quality assurance programs can be used to describe
      performance standards related to the quality and effectiveness of care.

PMID- 1391795
TI  - Antigen presentation in the skin: modulation by u.v. radiation and chemical
      carcinogens.
AB  - The skin provides an excellent model to investigate antigen presenting cells
      (APC) particularly using contact hypersensitivity responses. The skin has its own
      distinct APC of which Langerhans cells (LC) are the best characterized.
      Fluorescein isothiocyanate (FITC) has proved a useful reagent with which to
      follow antigen-labeled APC to draining lymph nodes, where they bind to T
      lymphocytes. Cluster formation appears to be a necessary component of the APC-T
      cell interaction. Both u.v. radiation and chemical carcinogens are able to alter
      LC in the skin, resulting in immunological tolerance when antigen is presented
      through such treated sites. The changes in APC function are linked mainly to the
      tumor promoting action of carcinogens. The nature of the APC that trigger
      suppressor circuits and the potential chemical mediators involved are discussed.
      These studies have important implications for the immunobiology of the skin and
      for cutaneous carcinogenesis.

PMID- 1391796
TI  - Antigen processing in the mucosal immune system.
AB  - The mucosal immune system is concerned with host defense along the moist surfaces
      of the body which have contact with the external environment. These sites contain
      specialized lymphoid structures which contain precursors for IgA-synthesizing B
      lymphocytes and immunoregulatory T lymphocytes which will determine whether oral
      tolerance or a strong immune response develops against antigens administered
      orally. The key step to antigen processing in the gastrointestinal tract involves
      its initial uptake from the gut lumen by specialized follicle associated
      epithelium called 'M' cells. M cells originate from adjacent crypt epithelium and
      are interspersed between the absorptive epithelial cells in the follicle
      associated epithelium. M cells cells have short, irregular microvilli, are
      closely associated with lymphocytes, do not have a prominent terminal web, and
      have only weak alkaline phosphatase activity but strong nonspecific esterase
      activity. M cells do not express surface MHC class II (HLA-DR) antigens. These
      cells take up macromolecules, viruses, bacteria and protozoa within 30 minutes
      from the initial presentation of the antigen to the intestinal lumen. After the
      initial uptake of antigen by M cells, the antigens are transported into the
      follicular areas to be processed by dendritic cells and brought into close
      contact with the antigen-specific precursors for IgA secreting plasma cells. The
      final result of M cell processing is the production of a vigorous secretory IgA
      response and local cell-mediated immunity with suppression of a systemic IgG, IgE
      and delayed-type hypersensitivity to orally-administered antigens.

PMID- 1391797
TI  - Antigen uptake and presentation by dendritic leukocytes.
AB  - Dendritic leukocytes are required for the initiation of T cell mediated immune
      responses. These cells, in different stages of maturation, are distributed
      throughout lymphoid and most non-lymphoid tissues. Immature cells may be
      localized predominantly within non-lymphoid tissues, and are responsible for
      endocytosis and processing of antigens. Inflammatory mediators are thought to
      promote their maturation and migration, via lymph and blood, into secondary
      lymphoid tissues. Here the mature cells present foreign peptide-MHC complexes to
      T cells, and deliver unique signals for T cell activation (immunostimulation).
      Within the thymus, however, these cells may be important for inducing T cell
      tolerance to self peptide-MHC complexes.

PMID- 1391798
TI  - Macrophages as accessory cells in the in vivo humoral immune response: from
      processing of particulate antigens to regulation by suppression.
AB  - The ability of macrophages to act as accessory cells for the antigen mediated
      stimulation of T lymphocytes has been unequivocally established in in vitro
      experiments. However, in vivo experiments are required to investigate whether the
      in vitro abilities of cells reflect their in vivo function. In order to study
      whether or not macrophages are required for the induction of antibody production
      in vivo, a liposome mediated macrophage elimination technique has been developed.
      Results obtained until now, have confirmed the role of macrophages in the
      induction of the antibody response against particulate antigens. However,
      macrophages are not required for the induction of the response against soluble
      antigens. Contrarily, in various organs they seem to regulate the latter response
      by suppression.

PMID- 1391799
TI  - Follicular dendritic cell and ICCOSOMES in germinal center reactions.
AB  - The development and destination of immune complex coated bodies (ICCOSOMES) was
      investigated at the ultrastructural level in the germinal centers (GC) of murine
      lymph nodes after secondary-immunization with horseradish peroxidase. Immediately
      after a booster injection, large amounts of immune complex (IC) were trapped on
      the surface of the cytoplasmic extensions of follicular dendritic cells (FDC).
      Cytoplasmic extensions, consisting mainly of FDC processes with associated IC,
      formed complex lamellar labyrinth-like structures (LBS). We describe here
      morphological changes of LBS. Lamellar or stationary LBS before the injection
      sequentially changed into distorted, filiform, glomerated and transitional LBS.
      Around day 1, IC-coated cytoplasmic extensions developed into glomerated LBS (G
      LBS) which were invaginated into their own cytoplasmic ends, which swelled up to
      several microns in diameter. Around day 2, tufts of the glomerated LBS were
      unlaced and dispersed as (ICCOSOMES) in the interstitium. Some ICCOSOMES were
      endocytosed by germinal center cells (GCCs) and transported to the Golgi
      apparatus and perinuclear space. These ICCOSOME-bearing GCCs were B220-positive
      and some produced specific antibody (spAb) in the perinuclear space indicating
      they are in the B cell lineage. ICCOSOME-ingesting GCCs are thought to be able to
      process the antigen and present it to T cells. This may be important in the
      development of plasma cells and memory cells which developed from the GC B cells.

PMID- 1391800
TI  - Targeting antigens to antigen presenting cells.
AB  - Antigen may be targeted to antigen presenting cells (APC) by conjugating the
      antigen to monoclonal antibodies directed against surface molecules on APC. By
      now several laboratories have shown that immunotargeting enhances humoral
      responses, depending upon the targeted ligand or cell type, with low doses of
      antigen and without the use of adjuvants. There is also preliminary evidence that
      the method may be used to bias immune responses in desired directions, possibly
      also to induce tolerance. In addition to its use as an experimental tool for
      exploring immune reactions the method could in the future also be clinically
      important, e.g. in vaccination. In this article we give a brief account on work
      so far published with this novel method and discuss possible mechanisms behind
      its immunopotentiating effects.

PMID- 1391801
TI  - Alterations of the p53 gene in Philadelphia chromosome-positive leukemia
      including chronic myelogenous leukemia and acute leukemia.
AB  - We analyzed the structural alteration of the p53 gene, by Southern blotting with
      conventional and/or pulsed-field gel electrophoresis, in patients with
      Philadelphia chromosome-positive leukemia (chronic myelogenous leukemia; CML, 34
      cases and acute leukemia; AL, 5 cases). We found an alteration of the p53 gene in
      one of 5 AL patients. Loss of heterozygosity was detected in two CML patients
      with i(17q) chromosome, but we could find no other alterations in the remaining
      CML patients.

PMID- 1391802
TI  - Coexistence of diabetes insipidus and idiopathic thrombocytopenic purpura.
AB  - Diabetes insipidus (DI) is a disorder characterized by polyuria, polydipsia and
      increased thirst [1] while pituitary DI is a syndrome that is known to result
      from deficient release of the antidiuretic hormone (ADH) [2,3]. Trauma to the
      neurohypophysis (operational or accidental) is the most common cause of DI.
      Primary or metastatic intracranial tumors are the second most common cause of DI.
      Among the less frequent causes are the granulomatous lesions or infections of the
      central nervous system, drugs and vascular lesions [2]. In 30-40% of the
      patients, there is no identifiable cause (idiopathic DI). Idiopathic
      thrombocytopenic purpura (ITP) is an immunologically mediated destructive
      thrombocytopenia. The clinical diagnosis is made after excluding the presence of
      other disorders that are known to be associated with shortened platelet survival
      [4]. In this paper two cases of DI and ITP are described.

PMID- 1391803
TI  - Comparative effects of G-CSF, GM-CSF and IL-3 on cytosine arabinoside- and
      daunorubicin-mediated cytotoxicity of acute myeloid leukemia cells and normal
      myeloid progenitors.
AB  - We carried out an in vitro study on the combined effects of three CSF (G-CSF, GM
      CSF and IL-3) plus the cycle-specific chemotherapeutic drugs [cytosine
      arabinoside (Ara-C) and daunorubicin (DNR)] on the proliferation and cytotoxicity
      of blasts and clonogenic cells (CFU-AML) in the AML-193 cell line, in AML
      patients and in normal bone marrow CFU-GM. The number of surviving blasts and/or
      DNA synthesis in blasts treated with CSF plus Ara-C or DNR was greater than those
      treated without CSF in the AML-193 cell line, and in some AML patients. On the
      other hand, the Ara-C- and DNR-mediated cytotoxicity of CFU-AML was not abrogated
      by CSF in any instance, but rather, it was significantly enhanced by all the CSF
      in the majority of instances. Although the enhancement was clearer when Ara-C was
      used, compared with DNR, there were no significant differences among the
      enhancing effects of the CSF. Under the same culture conditions as those for CFU
      AML, all of the CSF significantly enhanced the Ara-C-mediated cytotoxicity of day
      7 normal CFU-GM, although to a lesser extent than in CFU-AML. However, none of
      the CSF significantly affected the Ara-C-mediated cytotoxicity of day 14 normal
      CFU-GM or the DNR-mediated cytotoxicity of day 7 or day 14 normal CFU-GM. These
      results suggest that in the selection of a strategy entailing combined use of
      cycle-specific drugs plus CSF to increase the antileukemic effectiveness of
      chemotherapy in AML, G-CSF is preferable to GM-CSF or IL-3, since it has fewer
      potential clinical side effects, and that, furthermore, DNR may be as useful as
      Ara-C.

PMID- 1391804
TI  - Immunosuppressive factor produced by a B cell line derived from an adult T cell
      leukemia patient.
AB  - The immunosuppressive activity of culture supernatants from human T cell leukemia
      virus type I (HTLV-I)-infected cell lines was examined in vitro. Culture
      supernatants of both a HTLV-I-infected B cell line, IWS, established from an
      adult T cell leukemia (ATL) patient and a T cell line, MT-2, suppressed
      lymphocyte proliferative responses to stimulation with the mitogens
      phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM). The
      immunosuppressive factor was not cytotoxic for lymphocytes and did not inhibit
      the spontaneous growth of ATL cells. It inhibited interleukin-2 (IL-2) production
      by PHA-stimulated T cells and it arrested PHA-stimulated T cells at the G0/G1
      phase of the cell cycle and inhibited entry into the S phase. Furthermore, the
      factor significantly inhibited the expression of CD3, CD4, and IL-2 receptor (IL
      2R) alpha-chain (CD25) on PHA-stimulated T cells. These results suggest that the
      immunosuppressive factors produced by HTLV-I-infected cell lines might function
      in the regulation of normal lymphocyte proliferative responses, and that they
      could play some role in the induction of the immunodeficient condition observed
      in ATL patients.

PMID- 1391805
TI  - In vitro proliferative and differentiated responses of lymphoma cells to PHA and
      IL-4 in a patient with intermediate lymphocytic lymphoma.
AB  - We carried out in vitro B cell colony assays, with phytohemagglutinin-P (PHA-P)
      and IL-4, on B cells from one intermediate lymphocytic lymphoma (ILL) patient and
      four chronic lymphocytic leukemia (CLL) patients. Peripheral blood B cells from
      the ILL patient responded to PHA and IL-4, they proliferated, and differentiated
      into cells with plasmacytoid cell morphology. They lost the CD19 surface antigen
      after 10 day co-culture with PHA and IL-4. The bone marrow of this ILL patient
      contained atypical plasma cells with multiple nuclei. Peripheral blood B cells
      from the four CLL patients responded to PHA, but IL-4 did not increase PHA
      induced B cell colony formation in these cells. The CLL cells did not
      differentiate into plasma cells, and they were clearly different from the ILL
      cells in morphology, as shown by scanning electron microscope examination. Since
      this study was performed on cells from only one ILL patient, further examination
      of cells from many patients might be necessary to confirm the difference between
      ILL and B cell-type CLL.

PMID- 1391806
TI  - Mediastinal diffuse large cell lymphoma of B-cell type with azurophilic granules.
AB  - A case of diffuse large cell lymphoma of B-cell type with unusual azurophilic
      granules is reported. Lymphoma occurred primary in the upper anterior mediastinum
      and was suggested to be of thymic origin. Histologically, lymphoma cells showed
      diffuse proliferation and were large in size, frequently with multilobulated
      nuclei. In imprint preparations stained by May-Giemsa, most lymphoma cells had
      basophilic cytoplasm with azurophilic granules. Cytochemical studies showed the
      granules to be negative for PAS, peroxidase, acid phosphatase, and beta
      glucuronidase. Electron-dense granules and electron-lucent granules were found on
      ultrastructural analysis. The cells were characterized as B-cell type by
      immunophenotypes of L26+, CD20+, CD21-, CD22+, and PCA1+, the possession of
      surface monotypic IgA kappa immunoglobulin, and a genotype of immunoglobulin
      heavy and kappa light chain gene rearrangements.

PMID- 1391807
TI  - Ultrastructural analysis of platelet-like particles from a human megakaryocytic
      leukemia cell line (CMK 11-5).
AB  - Ultrastructural observations were performed to further characterize the human
      megakaryocytic leukemia cell line, CMK, and its subclone, CMK11-5. We found that
      particles derived from CMK11-5 cells had cytoplasmic projections and no nucleus,
      and that some particles contained alpha granules. Incubation with ADP induced
      fibrinogen receptors on the surface of these particles. Furthermore, the
      particles had glycoprotein Ib antigen on their surfaces, and attached
      nonreversibly to rabbit aortic subendothelium, showing associated morphological
      changes similar to those observed in normal platelets. CMK and CMK11-5 are the
      first megakaryocytic cell lines that have been found to release particles that
      have some of the same functions as normal platelets. In particular, CMK11-5 seems
      to be a useful model for studying megakaryocyte function.

PMID- 1391808
TI  - Replacement therapy in a patient with congenital prekallikrein deficiency
      undergoing surgery.
AB  - A patient with congenital prekallikrein (PK) deficiency underwent left endonasal
      radical ethmoidectomy and nasal polypectomy after receiving a transfusion of 6
      ml/kg body weight of fresh frozen plasma (FFP). His plasma PK activity was under
      1% before transfusion, and 46% after transfusion. The patient had no bleeding
      tendency during operation, but bled extensively from the wound 7 days after
      operation. At that time, his plasma PK activity was 3%. Since the bleeding could
      not be stopped simply by plugging his nasal cavities with tampons, he was given 3
      ml/kg body weight of FFP. As a result, his nasal bleeding rapidly decreased. No
      clinical sign of thrombotic complication was observed throughout the clinical
      course.

PMID- 1391809
TI  - N-RAS activation in the terminal stage of undifferentiated chronic
      myeloproliferative disease.
AB  - The relationship between activation of the N-RAS gene and the leukemic
      progression of undifferentiated chronic myeloproliferative disease (UCMPD) was
      investigated in a 71-year-old male. Hematologically, it was difficult to
      differentiate the UCMPD from chronic myelogenous leukemia. Chromosomal analysis
      revealed no Philadelphia chromosome (Ph1-), and DNA analysis revealed no BCR
      rearrangement (BCR-) either at the beginning or in the terminal stages of the
      disease. We performed a tumorigenicity assay, using NIH3T3 cells, and molecular
      analysis, using the polymerase chain reaction (PCR) and direct sequencing. The
      DNA of leukemic cells at the beginning of the leukemic progression did not show
      any abnormalities, but at the terminal stage of the disease the DNA showed a
      point mutation in codon 12 (GGT----GCT) of the N-RAS gene. Interestingly, a codon
      13 mutation (GGT----GTT) was also detected by tumorigenicity assay. These
      observations suggest that the activated N-RAS gene contributes to the hematologic
      progression of UCMPD.

PMID- 1391810
TI  - Myelodysplastic syndrome in a patient with a unique constitutional chromosome
      abnormality t(2;11) (q31;p13).
AB  - We present a case of myelodysplastic syndrome (MDS), which developed into an
      overt leukemic phase in a 15-year-old female with a rare constitutional
      abnormality [46,XX,t(2;11) (q31;p13)]. The patient entered complete remission
      after 3 months of chemotherapy. On chromosome analysis during remission, the
      t(2;11) (q31;p13) abnormality was detected in all metaphases of both the bone
      marrow cells and PHA-stimulated peripheral blood lymphocytes. Her father also had
      the same karyotype. This case seems to be of value as a reference for the study
      of the significance of constitutional chromosome abnormalities in MDS.

PMID- 1391811
TI  - [The diagnosis and staging of bronchial carcinoma with sectional imaging
      procedures].

PMID- 1391812
TI  - [Color-coded duplex sonography (angiodynography)].
AB  - Colour-coded duplex sonography is a relatively new method of diagnostic imaging.
      Compared with conventional duplex sonography it has advantages in respect of
      simplicity and speed in several applications. The main application of colour
      coded duplex sonography is for the detailed demonstration of a limited area. A
      comprehensive demonstration of blood vessels remains the province of angiography.
      Clinical applications include vessels in the neck, lateral soft tissue anatomy of
      the neck, arteries and veins in the extremities, haemodialysis shunts,
      transplanted kidneys and acute abnormalities in the scrotum. In the abdomen the
      method is of only limited application.

PMID- 1391813
TI  - [The course of the disease in endocrine orbitopathy. Magnetic resonance
      tomographic documentation].
AB  - MR imaging of the orbits was performed in 59 patients with untreated Graves'
      ophthalmopathy (follow-up exams were performed in 11 patients). T2-relaxation
      times of eye muscles were calculated and correlated with duration of disease.
      Elevated T2 times indicating eye muscle edema were found even if ophthalmopathy
      had been existing for more than one year. MRI documented specific eye muscle
      changes and transformation of oedema to fibrosis and fatty degeneration. MRI thus
      allows for standardized planning of therapy and follow-up in patients with
      Graves' ophthalmopathy.

PMID- 1391814
TI  - [The nuclear magnetic resonance tomographic differentiation of osteoporotic and
      tumor-related vertebral fractures. The value of subtractive TR gradient-echo
      sequences, STIR sequences and Gd-DTPA].
AB  - 42 patients with known malignancy and vertebral compressions underwent MRI.
      Sagittal T1-weighted spin-echo images pre and post Gd-DTPA, out of phase long TR
      gradient-echo images (GE) and short T1 inversion recovery images (STIR) were
      obtained at 1.0 T. The results were confirmed by histology (6/42) or clinical
      data (28/42) and follow up MRI studies (8/42). In 39 of 42 cases a correct
      differentiation between osteoporotic and tumorous vertebral compression fractures
      was possible by quantification and correlation of SE and GE signal intensities.
      Gd-DTPA did not improve differential diagnosis, since both tumour infiltration
      and bone marrow oedema in acute compression fracture showed comparable
      enhancement. STIR-sequences were most sensitive for pathology but unspecific due
      to a comparable amount of water in tumour tissue and bone marrow oedema.
      Susceptibility-induced signal reduction in GE images and morphologic criteria
      proved to be most reliable for differentiation of benign and tumour-related
      fractures. In the rare cases of single and nearly complete vertebral compressions
      with complete loss of bone marrow, differentiation with MRI was not possible.

PMID- 1391815
TI  - [Dynamic functional MRT of the cervical spine].
AB  - To obtain functional studies of the cervical spine, a device has been developed
      which allows MRI examinations to be carried out in five different degrees of
      flexion. T1 and T2* weighted FFE sequences were used. Dynamic functional MRI was
      performed on 5 normals and 31 patients (5 disc herniation, 4 whiplash injuries, 6
      spinal canal stenoses, 14 laminectomies and spinal fusions, 2 rheumatoid
      arthritis). The relationship of the spinal cord to the bony and ligamentous
      components in different degrees of flexion was particularly well shown in
      whiplash injury, spinal stenosis and postoperative situations.

PMID- 1391816
TI  - [The value of MR tomography in acute shoulder dislocations].
AB  - 24 patients up to two weeks after primary traumatic shoulder dislocation were
      examined at 0.5 and 1.5 T. Surgical and/or arthroscopic correlation was available
      in 13, CT-arthrographic correlation in 16 patients. A joint effusion allowing
      sufficient evaluation of the capsulolabral complex was present in 21/24 (87.5%)
      cases. 11/14 patients with combined dislocated detachments of the glenoid labrum
      and capsular lesions were subsequently operated upon. Marrow edema of the humeral
      head was found in 16/19 Hill-Sachs lesions and in 4/5 fractures of the greater
      tuberosity. Two patients presented with a lesion of the long biceps tendon
      associated with rotator cuff tears and were also subsequently operated upon. MRI
      performed shortly after primary traumatic shoulder dislocation allows a
      comprehensive evaluation of the intraarticular lesions and decisively influences
      further therapy.

PMID- 1391817
TI  - [Adhesive (retractile) capsulitis of the hip joint in diabetes mellitus. An x-ray
      histomorphological synopsis].
AB  - Adhesive (retractile) capsulitis of the hip joint is a rare complication
      (association) of (juvenile) diabetes mellitus. The clinical features, plain
      radiographic and CT findings and histomorphological appearances of this condition
      are described and attention is drawn to changes in the elastic tissue in the
      fibrosed capsule. Three diagnostic radiological features have been defined; in
      their presence, arthrography or diagnostic arthroscopy need not be performed.

PMID- 1391818
TI  - [The radiological findings in adamantinoma of the long tubular bones].
AB  - The radiological findings of adamantinomas of long bones are described in 22
      patients. The diagnosis was confirmed by a team of experts (pathologist,
      radiologist, orthopaedic surgeon) of the "Bone tumour study group" at the German
      Cancer Research Center. There were 12 male and 10 female patients aged 5 to 67
      years (most commonly in the second and third decade). In 21 patients the tibia
      was involved and in one patient the fibula. The tumour was nearly always in the
      diaphysis (20 cases). The most striking radiological feature was a diaphyseal
      lesion confined to the bone showing multicentric translucencies. The latter
      showed surrounding or central ring shaped or focal areas of increased density.
      The lesions tended to be longitudinal, averaging 11 cm (between 3 and 25 cm). All
      lesions showed a sclerotic margin separating it from normal bone, at least over
      part of the lesion. Expanding lesions were mostly separated from the soft tissues
      by a bony rim (18 cases).

PMID- 1391819
TI  - [Computed tomographic torsion-angle and length measurement of the lower
      extremity. The methods, normal values and radiation load].
AB  - Complex corrective osteotomies in the lower extremities require precise
      preoperative planning. Fifty patients (37 male, 13 female) with an average age of
      31 years (13 to 61 years) who had suffered fractures of the lower limbs and had
      been treated by osteosynthetic or conservative methods were studied, using a GE
      9800 Quick CT; accurate and reproducible measurements of the angles of torsion of
      the femur and tibia were obtained. Digital images were produced to standardise
      the planes of measurement and to measure the length of the limb. The normal
      extremities of patients older than 18 years showed internal torsion of -20.4 +/-
      9 degrees of the femur and external torsion of 33.1 +/- 8 degrees of the tibia.
      The most important clinical measurement is the intra-individual difference of the
      torsional angles. Amongst normals this is 4.3 +/- 2.3 degrees in the femur and
      6.1 +/- 4.5 degrees in the tibia. Consequently, only angles greater than 9
      degrees in the femur and 15 degrees in the tibia should be regarded as abnormal.
      Radiation exposure was measured by a LiF-thermoluminescence dosimeter on an
      Alderson phantom. Skin dose was 6.3 +/- 1.2 mGy and gonadal dose for females was
      2.5 +/- 0.3 mGy and for males 0.7 +/- 0.1 mGy.

PMID- 1391821
TI  - [Extrinsic allergic alveolitis in CT and HR-CT].
AB  - The CT changes on conventional and high-resolution CT in 14 patients with
      exogenous allergic alveolitis (EAA) were analysed retrospectively. There were 8
      patients with clinically subacute disease, 5 patients in a chronic stage and 1
      patient with acute EAA. The appearances and their distribution were examined.
      Seven of the 8 patients in the subacute stage showed a ground glass pattern and
      multiple nodules of less than 2 mm. All patients in the chronic stage showed a
      combination of fine infiltrates, small nodules and irregular linear densities;
      distortion of the pulmonary pattern was present in 3 cases. The patient with
      acute EAA showed diffuse dense areas of consolidation in both lungs as well as
      multiple nodules and a ground glass pattern. The CT appearances of EAA correspond
      with the basic micropathology and, within the clinical context, permit diagnostic
      classification.

PMID- 1391820
TI  - [Magnetic resonance tomography in pulmonary hypertension].
AB  - We examined 23 patients with pulmonary hypertension of varying aetiology by MRI
      and compared the results with those of right heart catheterisation. The best
      correlation was obtained between right ventricular mural thickness and mean
      pulmonary pressure (R = 0.91, p = 0.001). There was significant correlation (R =
      0.85, p = 0.001) for the diameter of the inferior vena cava, which was dilated in
      all patients with pulmonary hypertension. There was no significant correlation
      between mean pulmonary pressure and the diameters of the superior vena cava or
      the main pulmonary artery branches (R = 0.55 and 0.75 respectively, p less than
      0.05). Amongst functional measurements there was a correlation between right
      ventricular ejection fraction and mean pulmonary artery pressure (R = 0.71, p =
      0.001). There was no correlation between right ventricular end-systolic and end
      diastolic volume. In all patients with pulmonary hypertension, dynamic flow
      sensitive gradient echo sequences showed the presence of tricuspid insufficiency.
      A further semiquantitative criterion for the presence of pulmonary hypertension
      in 4 patients (17%) was an abnormal signal from the main pulmonary artery in
      early to mid-systole shown on T1-weighted transverse sections.

PMID- 1391822
TI  - [The value of the x-ray findings in the follow-up of the adult respiratory
      distress syndrome. A retrospective analysis].
AB  - Serial chest x-rays of 23 ARDS patients, taken in an 24 hour interval, were
      retrospectively analysed. Radiographic patterns of ARDS were divided into five
      stages and were related to corresponding parameters of respiratory status.
      Characteristic findings on chest x-ray films occurred after a short latency
      period following the clinical onset of ARDS. There was a close relationship
      between the time of maximum radiographic changes and maximum loss of lung
      function. The progression through successive radiologic stages was in many cases
      accompanied by a significant deterioration of functional parameters. Distinction
      between survivors and non-survivors was achieved while considering maximum
      radiographic abnormalities. The results suggest significance of serial chest x
      rays in diagnosis and course estimation of ARDS.

PMID- 1391823
TI  - [Magnetic resonance tomography (MRT) in pleural diseases. A comparison with CT
      and histopathological findings].
AB  - The MRI and CT appearances in 48 patients with histologically confirmed benign
      and malignant pleural abnormalities were compared retrospectively. Abnormal
      pleural changes were shown in 47 out of the 48 patients by high signal intensity
      of the pleura in T2-weighted sequences and in contrast enhanced T1-weighted
      sequences on MRI. CT showed abnormalities in 45 out of 48 patients. Delineation
      of pleural and pulmonary changes by CT was possible in 13 out of 23 cases, and
      pleural disease from effusions in 15 out of 28 cases. T2-weighted MRI was
      successful in 14 out of 23 and 4 out of 28 cases, respectively. T1-weighted
      images after contrast were successful in 20 out of 23 and 22 out of 28 cases,
      respectively. Indications of malignant pleural disease were the presence of
      mediastinal or circumferential involvement or involvement of the entire pleura,
      thickness of more than 10 mm and nodular changes. The most reliable sign of
      malignancy was infiltration of the thoracic wall and the diaphragm; this was
      better demonstrated by MRI (18 out of 19 and 2 out of 2 cases) than by CT (14 out
      of 19 and 0 out of 2 cases).

PMID- 1391824
TI  - [The tilted screen-cassette ("grid cut-off" effect). A problem of bedside
      thoracic diagnosis].
AB  - Tilting of a grid during portable radiography leads to uneven exposures, and
      errors greater than 3 degrees can lead to errors in interpretation.
      Differentiation from abnormal findings can be made by recognising exposure
      difference of extrathoracic comparable areas. The difficulties caused by tilting
      of the grid can be reduced by increasing the film focus distance and by using
      suitable grids. A new cassette holder with an integrated balance makes it
      possible to correct tilting of the grid rapidly and effectively. This results in
      improved image quality which can be applied not only to conventional exposure
      systems but is also of advantage when using digital methods.

PMID- 1391825
TI  - [Iliac artery occlusion: antegrade catheterization for stent placement].

PMID- 1391826
TI  - [Vertebral destruction by an abdominal aortic aneurysm].

PMID- 1391827
TI  - [The angiographic diagnosis of a rare esophageal arrosion hemorrhage from an A.
      lusoria].

PMID- 1391828
TI  - [A spinal extradural abscess in Crohn's disease].

PMID- 1391829
TI  - [The computed tomographic findings in chorea minor (Sydenham)].

PMID- 1391830
TI  - [Re: The report by U. Tosch et al.: The postoperative nuclear magnetic resonance
      study of the ankle joint after external syndesmorrhaphy. Vol. 155, December
      1991].

PMID- 1391831
TI  - [A contribution to P. Gerhardt: The indications for preoperative thoracic
      radiography. RoFo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 156 (1992) 409
      10].

PMID- 1391832
TI  - [A comment on the editorial by R. W. Gunther: Interventional radiology. RoFo
      Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 155, 1 (1991) 1-3].

PMID- 1391833
TI  - [Abstracts of the Experimental Radiology Meeting. Mainz, 24-26 september 1992].

PMID- 1391834
TI  - [Magnetic resonance tomography as the basis for biomechanical analysis. The
      simulation of the birth process as an example of the expanded information
      potentials of segmental imaging procedures].
AB  - A method is presented that enables the use of (static) informations from magnetic
      resonance imaging (MRI) for (dynamic) biomechanical analysis. Using a specially
      developed software MRI pixel matrices are colour-coded and--according to the
      principle of same density--line data are created. After sectional attribution of
      the resulting polygons a three-dimensional mesh of so-called finite elements is
      created which can then be used in deformation analysis. This method is
      exemplified by a project dealing with the simulation of birth mechanics, which is
      finally aimed at validating the results from radiologic pelvimetry. First
      analyses show that even under foetal head moulding conditions, being considered
      as normal, such sensitive structures as the cerebellum, brain stem as well as the
      ventricles with the plexus chorioidei are to be found within the maximum isobars
      within a range of 104-140 N(10.6-14.3 kp).

PMID- 1391835
TI  - [99m-Technetium-mercaptoacetyltriglycine (MAG3) for the demonstration of the
      kidney changes following extracorporeal shockwave lithotripsy. A prospective
      study of 117 patients].
AB  - Extracorporeal shock wave lithotripsy (ESWL) has become the treatment of choice
      for urinary calculi. 117 patients were studied prospectively with 99mTc
      mercaptoacetyltriglycine (MAG3) before and after ESWL. 79 (66%) of the 119
      kidneys treated had abnormal findings. Of these 63/119 (53%) had abnormal scans.
      41 (65%) had focal lesions with a delayed intrarenal transport. The remaining 22
      had a diffuse delay of intrarenal transport. A loss of relative renal function of
      3% and more compared to the pretreatment values was observed in 50/119 (42%)
      patients. 99mTc MAG3 should be done routinely together with radiologic tests (CT
      or MRI) before and after ESWL to select the patients at risk for post ESWL
      hypertension.

PMID- 1391836
TI  - [The technic of adrenal biopsy. Ultrasound versus CT as the guidance method].
AB  - Forty-seven needle biopsies of the adrenal glands have been performed under
      ultrasound or CT guidance. The aim was to clarify the best guidance method, the
      best approach, the choice of biopsy needle and possible complications. Analysis
      of the results provided the following answers: 1. A mass in the right adrenal can
      be biopsied under ultrasound control by a transhepatic approach. Small lesions of
      the left adrenal are best approached under CT guidance. In these cases a
      subcostal angled approach is advised. 2. Cutting biopsy needles provide better
      results than aspiration biopsy needles. 3. The complication rate of adrenal
      biopsies is very low if thin cutting needles are used.

PMID- 1391837
TI  - [The demonstration and staging of bladder carcinoma. A comparative study between
      magnetic resonance tomography, computed tomography and radioimmunoscintigraphy].
AB  - The purpose of the present study was to compare the effectiveness of MRI, CT and
      radioimmunoscintigraphy in the staging and detection of bladder cancers in 28
      patients. We distinguish two groups: Group I included the tumour stages CIS-T3A
      and the second group the deep infiltrative tumours T3B-T4. MRI was slightly
      superior to CT in respect of tumour staging (75% correct results as compared to
      63%). No understaging occurred with MRI, whereas in 22% of the cases the stage of
      the tumour was underestimated using CT diagnostics. Overstaging occurred in 25%
      of the MRI and 15% of the CT-diagnostics, respectively. RIS cannot distinguish
      the tumour groups, and hence this method is useful only for the detection of the
      primary tumour and metastases. In 77% of cases the tumour was detected and in 15%
      the tumour could be safely excluded.

PMID- 1391838
TI  - [Failed sclerotherapy trials with the V. spermatica interna. A retrospective
      analysis in 1141 patients with idiopathic varicocele].
AB  - From July 1988 until December 1990 1141 patients with left-sided idiopathic
      varicocele underwent phlebography of the spermatic internal vein, and
      percutaneous sclerotherapy with sodium morruate (Varicocid) was intended to be
      performed. In 125 of these patients sclerotherapy was not feasible. The reasons
      for this were analysed in a retrospective study. According to the anatomical
      situation of the spermatic vein, there were significant differences in technical
      success. In case of incompetent valve of the spermatic vein at the renal origin
      (type I, 2A, 3, 4A), selective probing and following sclerotherapy was possible
      in 97%. Anatomic variations with competent valve of the spermatic vein (type 0,
      2B, 4B) led to difficulties in selectively probing the vessel, and sclerotherapy
      was feasible in only 72.7%. In these angiographically difficult cases, spasm of
      the spermatic vein and/or perforation prevented sclerotherapy in 29 of 125
      patients.

PMID- 1391839
TI  - [Catheter-induced vascular lesions: a comparison of the diagnostic value of
      Doppler color sonography versus angiography].
AB  - One hundred and thirty-two patients with suspected lesions of the femoral
      arteries following diagnostic and/or therapeutic cardiac catheterisation were
      studied by colour Doppler sonography (CDS) and digital subtraction angiography
      (DSA) and the results were compared. CDS was unable to demonstrate 5 out of 23 av
      fistulae. Intra-arterial DSA showed all av fistulae found at operation. CDS
      showed lower reliability (95%) than DSA (100%) for the demonstration of
      pseudoaneurysms. CDS can indicate hematoma and thrombi in pseudo-aneurysms and
      their exact extent is better shown by sonography. Arterial dissections (2 cases)
      and intra-luminal thromboses or occlusions of the femoral artery (4 cases) are
      shown equally well by the two procedures.

PMID- 1391840
TI  - [Percutaneous aspiration embolectomy of the popliteal artery].
AB  - Twenty-eight patients (17 women, 11 men, average age 67 years, range 40-85 years)
      with embolic occlusions of the popliteal arteries were treated by aspiration
      embolectomy. 6 patients were in clinical stage IIb and 22 in stage III. In 25 of
      the 28 patients the occlusion was treated successfully. Complications could be
      treated non-surgically at the same time. 2 of the patients died within the first
      week of cerebral emboli, 2 further patients suffered recurrent emboli in the
      treated extremity during the first month. 17 patients who were followed up for
      six months were free of recurrences.

PMID- 1391841
TI  - [The regional blood flow in intracranial tumors: a comparison of HMPAO-SPECT with
      a newer magnetic resonance tomographic procedure].
AB  - We compared the value of gadolinium-enhanced first-pass MRI perfusion studies and
      HMPAO-SPECT for the assessment of regional cerebral blood flow in a prospective
      study of 23 intracranial tumour patients. In five tumours with homogeneous
      hypoperfusion and eight tumours with homogeneous hyperperfusion, tumour blood
      flow patterns in MRI and HMPAO-SPECT were similar. By contrast, in ten patients
      with inhomogeneous tumour blood flow pattern only MRI was able to differentiate
      between tumour areas with no or low flow, tumour tissue with high flow, and
      perifocal oedema with reduced flow. In HMPAO-SPECT, these inhomogeneous tumours
      were represented as areas of homogeneously reduced tracer retention corresponding
      to different tumour constituents and perifocal oedema. In conclusion, the high
      spatial resolution of MRI enables a detailed analysis of tumour blood flow.

PMID- 1391842
TI  - [Intracranial tumor-like lesions in children and young adults with multiple
      sclerosis].
AB  - Atypical early manifestations of multiple sclerosis (MS) are common in children
      and young adults. 6 patients (aged 5 to 33 years) were examined by MR because of
      confusing neurological manifestations. In addition to small MS lesions there were
      also large intracerebral lesions which, however, did not occupy additional space
      but which looked more like tumours or abscesses. The lesions were sharply
      demarcated cystic formations with margins that enhanced with contrast. The
      diagnosis of these lesions presents difficulties, the differential diagnosis
      including MS and its variants, neoplastic, infectious and vascular processes. MR
      can provide valuable diagnostic information.

PMID- 1391844
TI  - [The clinical value of magnetic resonance tomography in cystic space-occupying
      lesions of the mouth floor].
AB  - 11 patients with cystic lesions of the floor of the mouth were examined by MR
      imaging. Coronal slices provided an optimal visualisation of the lesions, but
      axial and sagittal slices added important information with regard to the exact
      topographic relationship between tumour and muscles. In particular, the mylohyoid
      muscle could be defined as a key structure. T1-weighted sequences enabled best
      visualisation of anatomic details, whereas T2-weighted sequences facilitated the
      primary diagnosis of cystic lesions. The contrast agent Gd-DTPA did not add
      information of significant diagnostic value. Our results indicate that MRI allows
      an exact visualisation of location and extent of cystic lesions and their
      relationship to surrounding muscles. We conclude that MRI is of high value in
      planning the operative strategy.

PMID- 1391843
TI  - [The determination of cerebral dopamine (D2) receptor density by using 123I-IBZM
      SPECT in Parkinson disease patients].
AB  - An alteration of the dopaminergic nigrostriatal system is believed to be the main
      pathogenetic factor of Parkinson's disease (PD). We report on our initial results
      on the determination of the post-synaptic dopamine-D2-receptor binding of 123I
      IBZM in patients with PD. Drug-native patients showed a significantly higher IBZM
      binding in the basal ganglia as compared to patients on specific dopaminergic
      medication. Age, duration of the disease and the severity of the disease do not
      seem to influence the IBZM-receptor binding. We conclude that 123I-IBZM-SPECT is
      an extremely useful tool for the evaluation of the functional state of cerebral
      dopamine-D2-receptors.

PMID- 1391845
TI  - [The magnetic resonance tomographic differential diagnosis between reactively
      enlarged lymph nodes and cervical lymph node metastases].
AB  - A prospective study was carried out involving 27 patients to determine whether
      MRT can distinguish between lymph node metastases and reactive lymph node
      enlargement. The results of MRT were compared with the pathological findings.
      Using T1 and T2 weighted sequences and proton density sequences it was not
      possible to differentiate between reactively enlarged lymph nodes and lymph node
      metastases. Following the administration of Gd-DTPA the observation of central
      hypo-intensity with marginal hyper-intensity is a reliable sign of a lymph node
      metastasis. Using the criterion of length greater than 10 mm for lymph node
      metastases results in a specificity of 32% and sensitivity of 75%. The use of the
      sonographic maximal/cross measurement quotient > 2 in the axial/coronary/sagittal
      dimension improves specificity and sensitivity to 94%.

PMID- 1391846
TI  - [Magnetic resonance tomography and magnetic resonance angiography in
      lymphangiomatosis].
AB  - Generalised lymphangiomatosis is a rare benign congenital abnormality of the
      lymphatic vessels with a complex pattern. 3 patients with different types of
      lymphangiomatosis were studied by MRT and MRA and histopathologically. All
      patients had multiple organ involvement in the abdomen, the skeleton and the
      skull. The basis in each case was lymphangiomatosis of capillary-cavernous,
      cystic or cavernous type. The results of MRT and MRA in diagnosing splenic,
      vascular and skeletal changes correlated accurately with operative findings and
      with the histopathological classification. In summary, MRT combined with MRA and
      using paramagnetic contrast media are the diagnostic methods of choice for the
      investigation of generalised lymphangiomatosis with multiple organ involvement.

PMID- 1391847
TI  - [Ultrasonic velocity measurements at weight-bearing and non-weight-bearing sites
      of the peripheral skeleton. The effect of physical activity in soccer players].
AB  - Ultrasound transmission velocity at the appendicular skeleton is determined by
      elastic properties of the bone as mass density. We evaluated ultrasound
      transmission velocity at the os calcis of both feet and at the proximal phalanges
      of DII and DIII of both hands in 51 male subjects. 28 of them were professional
      soccer players of the 1st German division, 11 subjects performed non-professional
      exercise in various athletic organisations regularly and 12 did not exercise at
      all. A significant difference in the speed of sound could be seen at os calcis,
      where the soccer players had higher velocities than the other groups. The
      differences between the groups at the upper and lower extremities suggest that
      changes in ultrasound transmission velocity are not only affected by structural
      changes in the aging skeleton, as it might be suggested by age differences, but
      by exercise. Physical exercise can change the properties (structure and/or
      density) of weightbearing bone and this can be detected by measuring ultrasound
      velocity.

PMID- 1391848
TI  - [Esophageal-bronchial fistula--a chance finding in the barium meal swallow].

PMID- 1391849
TI  - Epidermolysis bullosa: radiological patterns in childhood.

PMID- 1391850
TI  - Parosteal lipoma of the first metacarpal: CT demonstration.

PMID- 1391851
TI  - [An embolizing aneurysm of a "false" A. ischiadica. A description of a new
      variant of the A. axialis as a "persistent A. obturatoria"].

PMID- 1391852
TI  - [Lipid peroxidation in emotional stress in rats: correlation with parameters of
      open field behavior].
AB  - TBA-reactive products were measured in the brain, liver, and heart of Wistar rats
      in control conditions and after 24 h immobilization. Animals were subjected to
      the open field test before and after the immobilization. Behavior patterns,
      gastric mucosa alterations and MDA accumulation in organs suggested that
      immobilization as well as food and water deprivation were all strong stressor
      stimuli. Initial open field behavior characteristics were significantly
      correlated with MDA contents in various tissues under emotional stress.

PMID- 1391853
TI  - [Phrenic blood flow in cats with closed abdominal cavity].
AB  - By means of ultrasonic method, used in acute experiments on cats with closed
      abdominal cavity under nembutal narcosis, the authors studied the linear and
      volumetric blood flow velocity in left phrenic artery, the resistance of vascular
      bed of the phrenic artery, systemic blood pressure, respiration excursions during
      asphyxia, hypoxia, infusion of some biologically active substances. It was shown,
      that shortening of the diaphragm has definite influence on the blood flow and
      resistance of the vascular bed of the phrenic artery; the degree of the decrease
      of the blood flow in inspiration (on relation to the value of the blood flow in
      expiration, that passed as 100%) does not differ significantly in quiet and
      intensive respiration. Under the influences, the resistance of vascular bed of
      the phrenic artery decreases, the linear and volumetric blood flow increases,
      that indicates large reserve of the vascular bed of the phrenic artery for the
      increase of the blood flow.

PMID- 1391854
TI  - [Sex differences in response to stress in conscious and anesthesized rats during
      surgical stress].
AB  - Adrenal and plasma corticosterone levels under conditions of preoperative stress
      (removal from animal to experimental rooms, removal from a home cage, handling,
      weighing and injecting with saline) were more than 2-fold higher in female rats
      than in male ones. Females, compared with males, showed more pronounced decrease
      in corticosterone responses to preoperative stress and laparotomy under nembutal
      anesthesia, which blocked stress-induced emotional activation. One hour after
      recovery from anesthesia laparotomized females but not males, demonstrated a
      significant (5-fold) increase in plasma corticosterone level. The absolute values
      of plasma corticosterone in laparotomized females, compared with males, were 2
      fold lower under anesthesia but 2-fold higher after recovery from anesthesia. It
      is supposed that in females, compared with males, stress-induced emotional
      tension plays more considerable role in endocrine stress responses. This provides
      higher adrenocortical sensitivity to stress in conscious female rats than in male
      animals.

PMID- 1391855
TI  - [Interactions of mast cells and leukocytes in increased vascular permeability in
      the focus of inflammation].
AB  - On the model of acute infectious peritonitis in rats it is shown that the mast
      cell depletion affected the inflammatory focus vascular permeability mainly in
      the immediate phase of its increase. Leukopenia inhibited the permeability both
      in the immediate and delayed phases. The combined depletion of mast cells and
      leukocytes not only inhibited the degree of vascular permeability increase but
      strongly affected its kinetics during exudative phase of peritonitis. The results
      indicate that in the natural conditions of inflammation the mast cell-leukocyte
      interaction in the vascular permeability increase takes place.

PMID- 1391856
TI  - [Resistance and capacity function of blood vessels of the brain during activation
      of its cholinergic mechanisms].
AB  - Blood from the cat donor was perfused into the haemodynamically isolated cat
      brain. The changes of the vascular resistance and their capacity during the
      pharmacological activity of the endogenic cholinergic mechanism on the
      introduction of phosphacol into the bloodstream were investigated. Research has
      shown that the reduction of the activity of cholinergics leads to a decrease in
      pressure in the arteries of the brain and to an increase of the intercellular
      fluid absorption, caused by the neurogenic cholinergic influences. The
      possibility of a mediator realisation of the cholinergic influences on the brain
      vessels is discussed.

PMID- 1391857
TI  - [Contents of aldosterone and electrolytes in blood plasma and the myocardium of
      rats after single physical exertion during acute alcoholic intoxication].
AB  - It was proved in experiments with male Wistar rats that acute alcohol
      intoxication caused significant changes in electrolytes balance in blood plasma
      and myocardium remaining for a long time after ethanol injection. SPL test makes
      it possible to reveal inadequate reaction of blood plasma aldosterone in alcohol
      injected rats. This fact may be considered as the fact of involving extracardiac
      component of compensation of myocardial functional insufficiency conditioned
      mainly by electrolyte unbalance. The tolerance to physical loading is
      significantly higher in alcohol injected rats than in intact animals.

PMID- 1391858
TI  - [Effects of chronic experimental stress and endogenous opioids on
      histophysiological parameters of the thyroid gland].
AB  - In adult rabbits stress was modelled by electrostimulation of the hypothalamus
      ventromedial nucleus (15-hour-long session during 30 days) and medulla's raphe
      big nucleus which is one of the central places of the opioid peptides synthesis
      was irritated. It is revealed, that under stress thyroid gland responds by serum
      T3 increase in comparison with control animals with statistically significant
      variability of the T4 profile. Chronicity of the emotional agitation involves
      destructive changes in the thyroid parenchyma the hurting effect of the negative
      emotional factor is expressed less during opioid peptides complex activation. It
      is suggested that there are its own stress-limiting mechanisms in thyroid gland.

PMID- 1391859
TI  - [Biochemical bases of ftorafur-potentiating effects of perfluorodecalin, inducer
      of cytochrome P-450 dependent microsomal monooxygenases].
AB  - Activity of cytochrome P-450-dependent monooxygenase system is significantly
      lower in hepatoma H-2-73 and Lewis lung carcinoma-bearing mice as compared to
      that in control animals. An inhibition of the cytochrome P-450 system was
      observed after the injection of ftorafur. Treatment of the mice with
      perfluorodecalin markedly increased the antineoplastic activity of ftorafur
      determined by a loss of the leucocytes and of the weight hepatoma H-2-73- and
      Lewis lung carcinoma resistant to ftorafur alone.

PMID- 1391860
TI  - [Molecular mechanisms of antioxidant action of dalargin on the liver in
      experimental cholestasis].
AB  - Changes of antioxidant activity of dalargin in the liver after naloxone (100
      micrograms/kg) administration were examined in experiment on 144 rats with
      cholestasis. It was found that dalargin inhibited the activity of xanthine
      oxidase by 32-37% in different time periods after the injection. Dalargin and
      naloxone, when used in combination, had no effect on the enzyme activity.
      Glutathione-S-transferase activity rose by 38.0% and 21.8% on hour 1 and 3 after
      the injection, respectively, while simultaneous injection of dalargin and
      naloxone induced no changes in the enzyme activity after 1 hour, though decreased
      it by 36.8% and 26.4% on hour 3 and 5, respectively. Dalargin inhibited lipid
      peroxidation by 29-35%, simultaneous injection of dalargin and naloxone raised
      lipid peroxidation by 109.2%, 80.7% and 25.7% after 1, 3 and 5 hours,
      respectively. Dalargin injection elucidated a marked tendency to lowering of
      blood release of the liver-specific enzymes histidase and urokaninase in line
      with enhancement of their activity in the liver. A combined injection of dalargin
      and naloxone promoted high release of histidase and urokaninase in blood and did
      not change histidase activity in the liver in all cases. Urokanidase activity
      elevated in 5 hours. It was noticed that dalargin raised leu-enkephalin levels in
      the liver 3.5-fold 1 h after the injection. The reduced dalargin antioxidant
      effect coupled with naloxone pretreatment demonstrated indirect action of the
      neuropeptide on the liver via neuron receptors of the liver.

PMID- 1391862
TI  - [Effects of combined action of heavy metal salts and phenol on energetics of
      isolated rat liver mitochondria].
AB  - Experiments were carried out to investigate effects of heavy metal salts and
      phenol both alone and in different combinations on respiration rate and coupling
      of respiration and oxidative phosphorylation by rat liver mitochondria. Oxygen
      consumption measurements were obtained using a Clark electrode and lactate plus
      glutamate as substrates. It is shown that a 50% decrease of the respiratory rate
      was achieved in less concentrations of substances in the mixture compared with
      the effects of the individual substances. For respiratory control recovery by
      EDTA titration more amounts of complexion for model mixtures was necessary. The
      results evidence synergism of the substances responsible for a considerable
      increase in toxicity. Mitochondrial test-systems are suggested for rapid
      prognosis of toxicity of multicomponent mixtures of substances.

PMID- 1391861
TI  - [A comparative study on the effects of amiridin on learning and memory of old
      rats during passive avoidance test].
AB  - 18-month rats showed much less learning ability in comparison with that of 3
      month rats. 20-days treatment of old rats with amiridin, tacrine, and piracetam
      improved latency in passive avoidance test to the level of 3-month rats. The
      activity of acetylcholine esterase (AChE) from homogenates of old rat cortex was
      reduced as compared with that of young rats. After treatment with amiridin the
      activity of the enzyme remained unchanged, tacrine stimulate the decrease of
      activity of AChE while piracetam increased activity of AChE to the level of 3
      month rats. The aging of rats is followed by the reduction of unsaturated fatty
      acids, the increase of cholesterol content and the increase of microviscosity of
      membranes of brain synaptosomes. Multiple treatment with amiridin, piracetam and
      tacrine normalized these indices.

PMID- 1391863
TI  - [Effects of propranolol on the gastroduodenal myoelectrical activity].
AB  - The effects of propranolol on the myoelectrical activity of the stomach, pylorus
      and duodenum were investigated in chronic experiments on rabbits. During the
      first phase of propranolol action a positive gastro-chronotropic effect was
      accompanied by a negative cardio-chronotropic effect. The gastro-chronotropic
      effect was 3 times higher than cardio-chronotropic one. The second phase of the
      propranolol effect manifested with periodical fluctuation of the gastroduodenal
      myoelectrical activity during stable bradycardia. Marked reactivity of the gastro
      duodenum and periodical fluctuation of its activity are evidence of vital
      importance of the autoregulation mechanisms for gastroduodenal myoelectric
      activity.

PMID- 1391864
TI  - [Role of hematopoietic cells-precursors in the regeneration of hematopoiesis
      after cytostatic action].
AB  - Cyclophosphamide was injected at a dose of 150 mg/kg once to CBA mice and caused
      expressed hypoplasia of bone marrow hemopoiesis (decreased myelokaryocyte count,
      CFU-S and CFU-D) from day 1 of the experiment. The rise of CFU-S (8) and CFU-S
      (12) to a baseline level was noted on day 4 (the time of intensive regeneration
      processes), whereas CFU-D levels did not change. It is suggested that cytostatic
      action may trigger "shunt" hemopoiesis mechanisms which enhance differentiation
      of primitive hemopoietic cells and proliferative activity of mature hemopoietic
      elements.

PMID- 1391865
TI  - [Zinc contents of pancreatic islets in animals of various species after
      administration of diabetogenic agent, dithizone].
AB  - A decrease of zinc content in pancreatic islet was shown in animals which
      received diabetogenic agent dithizone. The changes of islet zinc content occurred
      mainly on account of insulin-producing cells and in coincidence with glycemia
      changes.

PMID- 1391866
TI  - [Specificity of the effect of polyene phosphatidylcholine depending on the mode
      of administration and animal species].
AB  - The effects of polyene phosphatidylcholine (PPC) treatment at oral and
      intravenous administration to rats and rabbits in hypercholesterolemic diet were
      studied. No aorta damage was observed in either of rat groups. But fatty liver
      appeared, and it was the greatest in rats, who received cholesterol and PPC. The
      result may be attributed to adaptive protection of peripheral tissues due to high
      experiment duration (18 months) in the state of active reverse cholesterol
      transport (RChT). No antiatherogenic effect was noted in rabbits at PPC
      administration (170 mg/kg), while its intravenous injection (50 mg/kg) resulted
      in marked reduction of plasma cholesterol level, elevation of HDL cholesterol and
      decrease of the extent of aorta damage. The conclusion is drawn on the ppc high
      antiatherogenic effect predominantly at intravenous administration, and on
      advisability of its use in cases of RChT deficiencies, as its activator.

PMID- 1391867
TI  - [Effects of morphine and naloxone administered to pregnant rats on the adrenal
      glands and testes of the offspring].
AB  - Relative testis and adrenal weights, testosterone and corticosterone levels in
      the blood were determined in 9-, 16-day and 2-month-old rats born to females
      injected with morphine (10 mg/kg/day), naloxone (10 mg/kg/day) or saline
      throughout the 15-18 days of gestation. Opioid receptors agonist morphine caused
      a long-lasting inhibition of the testes and activation of the adrenals. Saline
      injections to the females, that are known to be a stressor for them, also
      inhibited the testis of the neonatal offsprings. The block of the opioid
      receptors by the naloxone prevented the effect of prenatal stress on the testis,
      but inverted the negative correlation between the testes and the adrenals, that
      can be observed in the normal development.

PMID- 1391868
TI  - [Effects of phenothiazine and dibenzazepine derivatives on the muscarinic
      cholinergic system].
AB  - Interactions of some dialkylaminoalkyl (DAL) and dialkylaminoacyl (DAC)
      derivatives of phenothiazine and dibenzazepine with muscarinic cholinergic
      receptors (MR) of rabbit striatum and heart and rat brain were investigated. DAC
      derivatives were more active at brain and heart MR in some cases. The most active
      preparation was G-512, DA-analogue of chlorpromazine. Some cardiotropic
      properties of antianginal preparation nonachlazine may be connected with its
      central antimuscarinic activity.

PMID- 1391869
TI  - [Immunocorrecting properties of antibiotics in secondary immunodeficiency].
AB  - The study investigated immunocorrecting properties of penicillin G, streptomycin,
      gentamycin in cyclophosphamide--induced immunodeficiency in mice. It was
      determined, that antibiotics in sub-bactericidal doses possess pronounced
      immunocorrecting properties. This effect was observed in both humoral and cell
      mediated immune response.

PMID- 1391871
TI  - [Effects of IL-1 and TNF-alpha on the in vitro growth of fibroblasts].
AB  - Purified mouse IL-1 at doses higher than 5 u/ml strongly inhibits the growth of
      passaged rabbit bone marrow fibroblasts. Rec, human TNF-alpha at doses 0.05-3
      u/ml slightly stimulates and at higher doses inhibits the in vitro growth of
      passaged fibroblasts from rabbit and human bone marrow. At the same time the in
      vitro growth of human skin fibroblasts is stimulated by rec. human TNF-alpha.

PMID- 1391870
TI  - [Antiviral factor production by infected chick embryo fibroblasts].
AB  - The secretion of antiviral factor (AF) by infected cell cultures was examined.
      Activity of AF depended on the cell culture used. AF produced by infected chick
      embryo fibroblasts had maximal activity. No activity was registered in BHK-21
      cells, whereas human embryo fibroblasts and cell line Vero produced a low level
      of activity. Actinomycin D and cycloheximide prevented the production of AF. The
      results indicate that VEE virus-infected chick embryo fibroblasts produce AF
      which may be attributed to nonspecific factors of cell defense.

PMID- 1391873
TI  - [Athymic mice of the 101/HY strain with a new allele at the nude locus].
AB  - The spontaneous autosomal recessive mutation at locus nude (nuY) was discovered
      in 101/HY mice imperfect in respect to repair of induced chromosome damage and
      this is maintained in conventional conditions at RLEBM. Homozygous mutants have
      no hair and thymic differentiation. The new mutant form can be a valuable model
      for medical and biological experiments requiring T-cell immune deficiency.

PMID- 1391872
TI  - [Expression of human LSB 32/67 KD gene in E. coli and analysis of its
      interactions with laminin].
AB  - Earlier we have cloned cDNA coding for a polypeptide that reacts with monoclonal
      antibodies specific for some cytoskeleton structures. This gene is homologous to
      the laminin receptor 67 KD. However, cDNA suffices only for a polypeptide of 32
      Da, far smaller than the 67 rDa laminin receptor. We have constructed a vector
      that produces the fusion protein LBP-TrpE in the bacterial strain CAG-456. Our
      studies show that hybrid protein LBP-TrpE is able to interact with laminin. This
      result was confirmed by using following methods: immunoblotting, "ELISA" and
      affinity chromatography on laminin.

PMID- 1391874
TI  - [Erythrophagocytosis and pigment cells of the amphibian liver].
AB  - The ultrastructure of Kupffer liver cells of adult frogs collected in winter and
      Kupffer cells during amphibian metamorphosis when larval red cells are replaced
      by adult red cells were investigated. It was revealed that Kupffer cells of the
      animals investigated had very large size and consisted of either the whole
      senescent erythrocyte or many phagosomes with small electron dense granules
      resembling ferritin. Phagosomes are oriented among numerous vesicular and
      vermiform profiles of agranular endoplasmic reticulum and big Golgi complex.
      Comparing our morphologic evidence with data of the literature that granules of
      melanin are synthesized and localized in frog liver Kupffer cells, we came to
      conclusion that pigment cells were formed as a result of erythrophagocytosis and
      therefore they were the depo of catabolism products. The comparison of functions
      of melano-macrophage centers of fish liver and of pigment cells of amphibia liver
      were discussed.

PMID- 1391875
TI  - [Dependence of epidermal growth factor activation on its affinity and
      oligomerization].
AB  - Epidermal growth factor receptor (EGF-R) oligomerization has been followed on A
      431 cells using covalent labeling by 125I-EGF and EGF-dependent
      autophosphorylation of receptor-kinase. High molecular weight complexes
      corresponding to monomeric, dimeric, and trimeric forms of EGF-R are detected.
      The process of oligomerization occurs effectively at 37 degrees C while at 4
      degrees C no oligomer formation is detected. PMA or ATP treatment reduces the
      number of high-affinity EGF-binding sites but has no influence on dimer
      formation. Dimerisation of the EGF-R in the absence of the ligand has been
      established on formalin-fixed A-431 cells.

PMID- 1391877
TI  - [Development of a pseudointima in a synthetic prosthesis in experimental
      hypercholesterolemia].
AB  - Under study was the dynamics of formation of pseudointima in a synthetic lavsan
      prosthesis of the aorta of 32 rabbits, 22 of them were on the atherogenic diet.
      Against the background of experimental hypercholesterolemia the proliferation of
      cells and the obliteration of the vessel lumen were found to proceed more rapidly
      than in normal animals.

PMID- 1391876
TI  - [Effects of phytoadaptogens on biorhythms of indicators of the hemostasis system
      in dogs].
AB  - Circadian rhythms in dog hemostasis were studied in winter. The animals were fed
      with eleutherococcus and liquorice extracts with bread in different time of the
      day. Hemostatic investigations revealed chronosensitivity of hemostasis to the
      phytoadaptogens which is important for assessment of their chronopharmacological
      properties and prospects of their use.

PMID- 1391878
TI  - [Effects of hypothermia on the development of ischemic lesions of skeletal
      muscles in rats].
AB  - The influence of hypothermia on the development of the ischemic disorders was
      studied using allotransplantation of the rat skeletal muscle (m. lumbricalis) to
      the anterior chamber of the eye after different period of ischemia. The
      morphological and immunohistochemical (monoclonal antibodies to heavy chain of
      the fast myosin, PAP-method) data were found confirming that hypothermia (2-4
      degrees C) prolongs the period of the ischemic disorders first appearance by 5 h
      (from 6 to 11 h) if compared with development of ischemia in the muscle at 21-23
      degrees C.

PMID- 1391879
TI  - [Light optical and electron microscopic changes in striated muscle tissue under
      the effects of sea water and thymogen in experimental animals].
AB  - Effect of sea-water with t degrees +4 degrees to +8 degrees C with time of
      exposure from 30 minutes to 24 hours on pelvic extremities was studied in 200
      rabbits, optical and ultrastructural studies were carried out. It was revealed
      that effect of sea-water causes damage of striated tissues' structure and death
      of animals. Prophylactic injections of thymogen stabilized ultrastructure and
      raised survival, if time of exposure did not exceed 12 hours.

PMID- 1391881
TI  - [Formation of alcohol motivation under blockade of protein synthesis by
      cycloheximide].
AB  - The influence of protein blocker cycloheximide on ethanol intake in rats under
      condition of development of alcohol motivation was studied. It was found that
      intracerebroventricular injection of cycloheximide caused inhibition of alcohol
      intake in rats which had free choice between water and 20% ethanol solution. The
      blockade action of cycloheximide on the development of alcohol motivation was
      dependent on initial preference of ethanol in rats and was more strong in rats
      with originally low preference for ethanol.

PMID- 1391880
TI  - [Changes in gas composition of expired air during electric stimulation of the
      ventral medulla oblongata].
AB  - The experiments on urethane-anesthetized cats with the electrically stimulated
      ventral brain stem revealed that caudal ventral medulla at the depth of 1500
      microns possesses structures whose electrical activation increases the level of
      carbon dioxide in arterial blood and in the end portion of expirate, on the one
      hand, and decreases the oxygen content in expirate and arterial blood, on the
      other hand.

PMID- 1391882
TI  - [Changes in brain monoamine oxidase activity in conditioned passive avoidance
      reaction in rats].
AB  - Activity of the enzyme monoamine oxidase (MAO) and kinetic parameters (Km, Vmax)
      for the 5-hydroxytryptamine (5-HT) and dopamine deamination were examined in the
      brain of rats with conditioned passive avoidance recall. Changes of the 5-HT and
      dopamine deamination were found in amygdala, striatum and frontal cortex. MAO
      activity was not changed in hippocampus. In amygdala the rate of 5-HT deamination
      was significantly increased and kinetic studies revealed increased affinity of
      the enzyme for 5-HT. The metabolism of dopamine in amygdala was unchanged. In
      frontal cortex the deamination of 5-HT was not changed, but the dopamine
      deamination significantly decreased. This decrease was due to lowering of MAO
      affinity for dopamine. In striatum the metabolism of both 5-HT and dopamine was
      reduced, and kinetic studies showed the lowering of Vmax for 5-HT and dopamine
      deamination.

PMID- 1391883
TI  - [Effects of neuropeptide Y on rat body temperature in normal conditions and after
      ethanol administration].
AB  - It was shown that intracerebroventricular (icv) administration of 2 micrograms
      neuropeptide Y (NPY) increased the rectal temperature in rats 2.5 hours
      postinjection. During 5 days we analysed dynamics of the effect of NPY on alcohol
      induced hypothermia in this particular interval. 2 micrograms of NPY were given
      daily 30 min prior to 25% solution of ethanol (3 g/kg weight rat) intraperitoneal
      injection. It was found that NPY can prevent the attenuation of alcohol
      hypothermia on the 3-d and 4-th injection day. It was supposed that the
      inhibitory effect of NPY on the development of alcohol tolerance may be due to
      the capacity of NPY to increase food behavior. So it's known that activation of
      other competitor motivation may inhibit the development of alcoholism.

PMID- 1391885
TI  - [Study of blood and lymph in experimental myocardial ischemia and arterial
      hypertension].
AB  - The peripheral blood and central lymph of rats under experimental myocardial
      infarction was studied by means of light microscopy and electric conductivity
      measurement. Both hypertensive rats and animals 3 days after myocardial
      infarction had similar quantity of neutrophils in peripheral blood. Lymph cells
      count of hypertensive rats by middle lymphocytes is similar to the animals 1 day
      after myocardial infarction. The correlation between lymph and blood electric
      conductivity and its cell composition was noted.

PMID- 1391884
TI  - [Effects of magnesium and nickel ions on penicillin-induced focal epileptic
      activity in the cerebral cortex of rats].
AB  - In experiments on freely moving male Wistar rats on the model of penicillin
      induced focal epileptic activity (EA) (the application onto the sensorimotor
      cortex of a filter paper soaked with benzylpenicillin sodium salt solution) it
      was shown that addition of MgSO4 (series 1) and NiCl2 (series 2) into the
      solution of penicillin significantly weakened EA. The combination of Mg2+ and
      Ni2+ with penicillin (series 3) produced a more significant suppression of EA as
      compared with separate application of the above-mentioned ions: the latency
      period of appearance of interictal discharges (IID) increased, the frequency and
      amplitude of IID decreased much more, no ictal discharges appeared in any animal,
      the duration of epileptic foci reduced to a much greater extent. This effect can
      be explained by the blockade of Ca current by the above-mentioned ions. One can
      suppose that the amplification of antiepileptic effects of combined action of
      Mg2+ and Ni2+ was due to an increase in the number of blocked voltage-dependent
      and NMDA-operated calcium channels.

PMID- 1391887
TI  - [Effects of carnosine on systemic hemodynamics and myocardial metabolism in rats
      in the early postresuscitation period].
AB  - It was demonstrated in experiments on male rats that acute lethal blood loss and
      subsequent resuscitation after 4- and 6-min clinical death induce lipid
      peroxidation processes, decreased antioxidant enzyme activity, cause activation
      of anaerobic glycolysis in the myocardium. This metabolic heart impairment causes
      hemodynamic instability in postresuscitation period. 25 mg/kg of carnosine
      injected during resuscitation decreased functional-metabolic heart impairments
      and hemodynamic disarrangement as well as early postresuscitation lethality. The
      authors attribute positive carnosine effect to its significant antioxidant
      activity.

PMID- 1391886
TI  - [Use of 2,4-dinitrophenol for immunosuppressive action on the recipient in
      implantation of fetal organs in mice].
AB  - In experiments performed on 118 white mice and 10 laboratory rats, it was shown
      that cutaneous application of 2,4-dinitrophenol microdoses once a week around the
      sites of fetal organ implantation leads to a significant prolongation of the
      implant life with minimal trouble for the recipient's health. The maximal effect
      was reached with 10(-3) M concentration of DNP, the applications beginning 2-3
      weeks before fetal pancreas implantations.

PMID- 1391888
TI  - [Possibilities of restoration of the regional lymphatic channel by the use of
      sorbents in the treatment of experimental generalized purulent peritonitis].
AB  - Regional lymphatic bed in local application of mineral sorbent SUMS-2p in 80
      white noninbred rats with experimental generalized purulent peritonitis is
      studied with the use of indirect intravital lympho-roentgenography. The
      correlation between lympho-dynamics and generalized purulent peritonitis stage
      was observed. It is shown that the peritoneo-sorption with the mineral sorbent
      SUMS-2p led to early restoration of lympho-drainage.

PMID- 1391889
TI  - [Effects of the respiratory epithelium on the tracheal smooth muscle in guinea
      pigs].
AB  - We studied the influence of respiratory epithelium on tracheal smooth muscle tone
      of guinea pigs. Mechanical removal of the epithelium induced an increase of the
      contractile response to histamine. In preparation of smooth muscle previously
      contracted by histamine, isoproterenol induced dose--dependent relaxation, the
      level of which was significantly greater in tracheal smooth muscle with
      epithelium than without it. These results suggest an important role of
      respiratory epithelium on the contractile activity of smooth muscle.

PMID- 1391891
TI  - [Beta-mannosidase of trophoblast and humana skin fibroblasts].
AB  - Conditions for assay of beta-mannosidase activity in human chorionic villi were
      studied using the fluorogenic substrate 4-methylumbelliferyl-beta-D
      mannopyranoside. Comparison of the biochemical properties of the chorionic villi
      beta-mannosidase with those of the enzyme from human cultured fibroblasts showed
      their similarity. Like the enzyme from skin fibroblasts, the chorionic villi beta
      mannosidase had rather high activity. Both enzymes had virtually the same pH
      optimum (4.2-4.7) and Km value. The data presented suggest that chorion biopsy
      specimens can be used for prenatal determination of beta-mannosidase activity at
      the early stage of development.

PMID- 1391890
TI  - [Effects of synthetic antioxidant ionol on bioelectric activity of cardiomyocytes
      and arrhythmia in global ischemia and reperfusion of the isolated rat heart].
AB  - Isolated rat hearts were subjected to global ischemia (15 min) and reperfusion
      (20 min). Transmembrane potentials were recorded on the epicardial surface and
      contractile force was measured. Ischemia reduced the resting potential, the
      action potential (AP) amplitude and the AP duration (APD) in control animals.
      Pretreatment with synthetic antioxidant ionol (BHT, 50 mg/kg, per os) didn't
      influence the time course of changes in the resting potential and AP amplitude
      during ischemia, but significantly increased APD. In the pretreated group, 5 min
      after the aorta clamping, the APD at 50% and 90% levels of repolarization was 36%
      (p less than 0.05) and 13% (p less than 0.1) higher in comparison to the
      preischemic level and 10 min after clamping by 27% (p less than 0.1) and 29% (p
      less than 0.05), respectively. By the end of ischemia in the pretreated group,
      APD re-decreased almost to basal level, but in control group, it remained
      decreased. During reperfusion BHT improved the recovery of bioelectrical activity
      and the contractile function. The BHT 10-fold reduced the malignant arrhythmias
      duration and 2.5-fold the incidence of ventricular tachycardia and fibrillation
      during reperfusion. These results indicate that the induced by BHT increase in
      APD can contribute to the mechanism of BHT antiarrhythmic action.

PMID- 1391892
TI  - [Study of pantothenic acid derivatives as cardiac protectors in a model of
      experimental ischemia and reperfusion of the isolated heart].
AB  - An isolated heart model with experimental ischemia and reperfusion was used to
      show effective decrease in lactate, increase in ATP content and prevention of
      conjugated dienes accumulation in the myocardium by derivatives of pantothenic
      acid: panthenol (9.0 mg/kg), calcium pantothenate (15.6 mg/kg) and by these ones
      applied simultaneously as ingredients of perfusate (25 microM) in postischemic
      period. In that way derivatives of pantothenic acid should be regarded as cardiac
      protectors.

PMID- 1391893
TI  - [Effects of desferrioxamine (desferal) on the formation of epileptic focus in
      rats after subdural injection of blood].

PMID- 1391894
TI  - [Hemispheric asymmetry of the nigrostriatal system of the brain in rats
      genetically predisposed to catalepsy].
AB  - Hemispheric asymmetry of nigro-striate system in a strain of rats GC bred from
      Wistar for a predisposition to cataleptic reaction was studied by means of
      biochemical and morphological methods. Hemispheric asymmetry was found in GC and
      Wistar rats with respect to aminopeptidase activity in neurons of caudate
      nucleus, with a more pronounced left-side increase in GC rats, the asymmetry
      index being 13.7%. Acetylcholine esterase activity in subcellular particles of
      caudate nucleus showed an inversion of asymmetry with higher activity in the left
      hemisphere of Wistar and right hemisphere of GC rats, and asymmetry index of
      15.5%. With respect to the number of astroglia cells in S. nigra, and astroglia
      and oligodendroglia in N. accumbens there was also an inversion of asymmetry in
      GC rats who had more cells in the structures of the left hemisphere, whereas
      Wistar rats had more in the right hemisphere. The asymmetry index was high and
      equal to 29.8% for astroglia in S. nigra, and 17% for astroglia and 21.4% for
      oligodendroglia in N. accumbens. However, in S. nigra the number of neurons and
      oligodendroglia cells was equally increased in the right hemisphere in GC and
      Wistar rats. The data suggest that the mechanism of hereditary pathology of brain
      nigro-striate system involves both enhancement and inversion of the hemispheric
      asymmetry.

PMID- 1391895
TI  - [Pharmacokinetics of antipyrine, nifedipine and diazepam in experimental
      myocardial infarct].
AB  - It has been shown, that antipyrine, nifedipine, diazepam pharmacokinetics changes
      in different ways after myocardial infarction. On day 7, 14, and 21 after
      myocardial ischemia antipyrine T1/2 increased considerably, and antipyrine Cl and
      Kel decreased. Nifedipine T1/2 increased on day 7 only. There were no diazepam
      pharmacokinetic changes during restoration period. However, microsomal diazepam
      metabolism changed significantly. Diazepam hydroxylation increased on day 7 of
      myocardial infarction, and on day 14 and 21 did not differ from the control.
      Diazepam metabolites content changed considerably during restoration period.
      Under myocardial infarction cytochrome P-450 isoenzymes, oxidizing present
      substances seem to be altered to different extent.

PMID- 1391897
TI  - [Action of GABA-positive preparations on uterus-stimulating effects of activating
      neuromediators, prostaglandin F2 alpha and oxytocin].
AB  - Experiments on isolated strips of the non-pregnant rabbit and rat uterus showed
      the ability of dopamine, noradrenaline, serotonin, acetylcholine, prostaglandin
      F2 alpha, oxytocin to increase the uterine strips contractile activity. On the
      other hand, GABA, GABAB receptors agonist phenibut and diazepam inhibit the
      stimulating effects of the above mentioned substances, thus showing the
      properties of physiological antagonists of these neuromediators, prostaglandin
      and oxytocin.

PMID- 1391896
TI  - [Reduction of voluntary alcohol consumption under the effects of prolonged-action
      zinc].
AB  - It was revealed that an involuntary rats' intoxication with 10% ethanol solution
      during 8 months caused a reduction of zinc content in the brain. A subcutaneous
      depot administration of highly dispersed zinc powder in a dose of 5 mg/kg reduced
      ethanol consumption under conditions of free choice for two weeks. This effect of
      the preparation was associated with normalization of zinc content and increase of
      a malondialdehyde level in the brain.

PMID- 1391898
TI  - [Thymectomy and splenectomy of adult mice have no influence on the level of
      suppressor activity of T-lymphocytes specific to antigens of H-2 complex].
AB  - I.v. immunization of mice with irradiated (1500 rad) allogeneic spleen cells
      induces T cells specific to histocompatibility antigens and capable to suppress
      proliferation in mixed lymphocyte cultures. The lymph node cells appeared to be
      almost as capable as spleen cells of producing suppression. Splenectomy
      experiments showed that the spleen is not essential for induction of suppressive
      activity of T cells. The precursors of T cells with suppressive activity do not
      belong to the pool of short-living cells as they are insensitive to adult
      thymectomy, produced 6 weeks before immunization.

PMID- 1391899
TI  - [Serum antibodies to brain protein antigens in cerebral palsy in children].
AB  - Using special brain antigen test-system ELITEST-24, ELISA assays of the serum of
      children with cerebral palsy were conducted. The data obtained were compared to
      relevant characteristics of the sera from neurologically and somatically healthy
      persons and patients with diagnoses of multiple sclerosis, schizophrenia,
      epilepsy and hepato-cerebral dystrophy according to special PC program VIZUAL and
      DIAGNOST. High specificity of the cerebral palsy anti-brain antigens reactivity
      was revealed by ELITEST technique. Moreover, the comparison of the mother-child
      pair immunoreactivity has been conducted. Evidence for hypothesis of
      epigenetically performing of children antibodies repertoires by mother-during
      pregnancy immune status were obtained. Possible immunopathologic mechanisms of
      the disease are discussed.

PMID- 1391901
TI  - [Induction of stromal cell transformation in xenografts of human colonic cancer].
AB  - Two transformed stromal cell lines FM-7 and FR-7 were obtained from human
      xenografts of colon tumor (HCT-7), propagated in nude mice and nude rats,
      respectively. These two cell lines were confirmed to be murine and rat's by a
      cytogenetic study and were tumourigenic in BALB/c nude mice with the morphology
      of fibrosarcoma. Human DNA sequences were not detected by hybridization with
      pBlur8 probe in DNA of FR-7 cell line grown in vitro. These results indicate that
      human cancer cells from xenograft HCT-7 can induce malignancy in adjacent normal
      cells of nude mice and nude rats in the absence of DNA transfer.

PMID- 1391900
TI  - [Effect of T-activin on the formation of conditioned reflex and manifestations of
      unconditioned reflex of avoidance in August strain rats].
AB  - It has been revealed that intraperitoneal injection of T-activin (humoral factor
      of the thymus) to August rats leads to more rapid and stable conditioned reflex
      formation to a sound and to a decrease of avoidance time when electric current is
      given to a shuttle chamber. Furthermore, less amount of uneffective series in
      testing unconditioned avoidance is registered in the test animals. A positive T
      activin effect on conditioned reflex formation and unconditioned reflex
      manifestation is probably connected with its ability to alter hippocampus
      functional parameters and (or) with anti-stressor properties of the preparation.

PMID- 1391902
TI  - [Stimulation of skin wound contraction and epithelialization by soluble collage].
AB  - It is found that local applications of the unguent with soluble collagen, but not
      solution of the collagen, stimulate healing of erosions and full-thickness
      excision wounds in the rat skin. Not all the stages of healing were stimulated,
      but only two of them--contraction and epithelialization.

PMID- 1391903
TI  - [Effects of helium-neon laser on regeneration capacity of skeletal muscles of
      adult guinea pigs].
AB  - The muscle regeneration was studied in across-cut gastrocnemius muscle of adult
      guinea pigs. Both hind guinea pig legs were exposed to laser therapy (3-9
      procedures for 5 min each) after operation. It was shown that laser therapy
      accelerated fibrin resorption and wound healing, decreased the muscle fiber
      degeneration, increased DNA and RNA synthesis in regenerating tissues, stimulated
      regenerative muscle fiber capacity. However, the regenerating muscle tissue did
      not connect both muscle stumps, and the narrow connective tissue scar was formed.
      Before it was shown that the same laser therapy conditions were more effective
      for rats. Probably, the stimulating effect of laser rays on regenerative tissue
      ability depends on species peculiarities of animals.

PMID- 1391904
TI  - [Ultrastructural and morphometric analysis of the Paneth cell reaction to
      administration of cholera toxin].
AB  - Experiments were made on 40 immature guinea--pigs which were divided into two
      groups. 20 animals received intraduodenal injections of cholera toxin and 20
      others were injected normal saline (groups I and II, respectively). Group I
      animals exhibited a rapid fall in one--cell secretion of XS recorded on hour 6-12
      after the injection of cholera toxin. Inhibition of functional activity was
      associated with defected synthesis of granules in the cells of Paneth.

PMID- 1391905
TI  - [A new method of a morphometric study of the kidney using a computer-assisted
      morphometric complex "Diamorph"].
AB  - The use of a computer--based morphometric complex "DIAMORPH" for automated
      morphometric analysis of renal glomeruli is described. By combining the
      principles of morphological and functional approaches to diagnosis with the
      capabilities of present--day research equipment, a new informative morphometric
      parameter--the extent of capillary--mesangium contact--has been identified. With
      this parameter and its derivatives, it has been possible to differentiate, in a
      statistically significant way (p less than 0.01), healthy subjects (controls)
      from patients with manifest diabetes mellitus of up to I year in duration who
      could not be distinguished through light microscopic or conventional morphometric
      studies.

PMID- 1391907
TI  - [Obtaining and morphological characteristics of primary monolayer cell cultures
      of human somatotropinomas].
AB  - This paper describes the development of method of preparing cell suspension
      obtained from surgical material of patients with pituitary adenomas and
      acromegaly as well as the procedure of subsequent long-term cultivation in
      monolayers of the cells isolated. As judged by visual inspection and measurement
      of growth hormone and prolactin secretion, tumor pituitary cells kept viability
      and functional activity for at least 6 days of growing in vitro.
      Immunocytochemical visualization of somato- and lactotrophs of the same
      histological preparations permitted us to show that vast majority of cultured
      cells is represented by somatotrophs; however, a small portion of cell population
      is represented by lactotrophs and lactosomatotrophs. The peculiarities of
      cytoarchitectonics in two types of cell cultures of human somatotropinomas were
      studied.

PMID- 1391906
TI  - [Effects of different doses of hyperbaric oxygenation on morphology and
      transcription of cortical neurons of rats with experimental cerebral ischemia].
AB  - Its effect of hyperbaric oxygenation (the doses 1.2 and 2 ata) on cortical
      pyramids of the rats with one-or both-side ligation of common arteria carotis 2.5
      or 24 hours after operation was studied. The neuron survival and transcription
      activity were estimated. In all experimental situations except the most serious,
      e.g. 24 hours after the both-side artery ligation, the dose 2 ata was more
      effective. On the contrary, in most serious cases the dose 1.2 ata or applying in
      the baro-camera the air instead of oxygen provided the better result.

PMID- 1391908
TI  - [Effects of low intensity infra-red laser irradiation on ultrastructure and
      proliferation of liver cells in experimental hepatitis and cirrhosis].
AB  - With the aid of light, electron transmission and scanning electron microscopy and
      radioautography and stereometry, the influence of low-intensive laser irradiation
      (LILI) (infrared) was studied in normal rat liver and in experimental cirrhosis
      and hepatitis. It was revealed that arsenide-gallium laser irradiation causes the
      change of intracellular structure. These changes show the intensification on
      their specific function manifest in an increase of relative volume of
      intracellular structures. The changes of microvessels show the activation of
      microcirculation. The elevation of the index of the labelled nuclei testify to
      increased proliferation. The similar influences of LILI on the liver
      ultrastructure and proliferation in hepatitis and cirrhosis are accompanied by
      the reduction of the pathological changes of the liver--the hepatocytes oedema,
      granular, vacuolar and fatty dystrophy.

PMID- 1391909
TI  - [Enzyme profile of human musculus triceps surae fibers under conditions of local
      endurance training (a quantitative histochemical study)].

PMID- 1391910
TI  - [Ultrastructural signs of microcirculation of the articular cartilage in
      rheumatoid arthritis].

PMID- 1391912
TI  - [Histophotometric characteristics of structural-metabolic heterogeneity of
      hepatocytes in acute hemorrhage and pulmonary artery thromboembolism].
AB  - Basing on the data obtained at early autopsies, we compared the structure and
      metabolism of liver acini in acute blood loss and pulmonary artery
      thromboembolism. Morpho- and pathogenetic impairment of hepatocytes of various
      acinic zones was correlated and studied histo-enzymatically.

PMID- 1391911
TI  - [Morpho-biochemical study of catecholamine metabolism in the myocardium of dogs
      with fibrillation and autolysis].
AB  - The balance of catecholamines (CA) and their metabolites in the canine heart
      during myocardial fibrillation and 1, 2, 3, 4, 5, 6 hours after death was
      studied. The fibrillation was caused by low myocardial electrostimulation. The
      comparative neuro-morphometric analysis of the CA-containing structures in 1 and
      5 min of the fibrillation and the determination of the norepinephrine, its
      precursors and metabolites by HPLC-ED method was done. There was an increase of
      the myocardial norepinephrine (20%), 3-4-dihydroxyphenylethyleneglycol (25%) and
      decrease of the dopamine (50%) contents without any qualitative changes of CA
      metabolism. Autolysis leads to the successive decrease of the norepinephrine and
      dopamine contents without any qualitative changes of the CA metabolism too. These
      data suggest that autopsies could be used for the determination of the myocardial
      CA content and the qualitative characteristics of the CA metabolism before death
      in those who died suddenly.

PMID- 1391914
TI  - [Neurohistological characteristics of regeneration of the ends of the injured
      nerve under measured traction].
AB  - A resection of sciatic nerve in 25 dogs was performed out and the ends of cut
      nerve were connected by sutures with special apparatus for quantified traction of
      nerve stumps. 5 days after resection traction was stented at the rate of 0.25 mm
      twice a day. A histological analysis performed in 5, 12, 19, 26, 33 days after
      resection an 2-12 months after nerve suture has shown that stress strain effects
      on intercalation of nerve structures (Ilizarov's effect). Newly formed Schwann
      chains free of products of axonal and myelin disruption have got a perfect
      longitudinal orientation and that's why can be considered as an optimum
      substratum for axonal regeneration.

PMID- 1391913
TI  - [Structural-metabolic characteristics of acute hepatic failure].
AB  - Basing on early autopsy data, the study was made of structural and metabolic
      characteristics of the liver in marked intoxication and blood loss. Histologic,
      histoenzymatic and biochemical methods were used to evaluate morpho- and
      pathogenesis of acute liver failure arising in the above conditions.

PMID- 1391915
TI  - An advance in implant-supported overdentures utilizing rigid attachments.
AB  - Two cases are described in which a bar overdenture design is utilized to meet the
      aesthetic, phonetic, and functional requirements of patients with one or more
      edentulous arches. The implant-supported overdenture can be a creative solution
      for anatomic and skeletal discrepancies.

PMID- 1391916
TI  - Treatment of a discolored, endodontically treated tooth with home bleaching and
      composite resin.
AB  - Internal bleaching is frequently used to treat discolorations of endodontically
      treated teeth, and home bleaching of stained vital teeth has also become popular.
      This article describes a case in which carbamide peroxide home bleaching was used
      to enhance the appearance of an internally bleached, endodontically treated
      tooth.

PMID- 1391917
TI  - In-office fabrication of indirect composite-resin restorations.
AB  - Indirectly fabricated composite-resin inlay and onlay posterior restorations are
      becoming more popular. By utilizing a flexible die material, these restorations
      can be expeditiously completed by the dentist or by a well-trained dental
      auxiliary, often in one appointment.

PMID- 1391918
TI  - Placement of implants into fresh extraction sites using a resorbable collagen
      membrane: case reports.
AB  - The ability to place endosseous implants has recently expanded to include
      placement in fresh extraction sites. In this technique, the use of some form of
      occlusive membrane is often beneficial. In the future, resorbable membranes may
      provide a predictable clinical result in these types of cases.

PMID- 1391919
TI  - Provisionalizing periodontally involved dentition with implants.
AB  - Many patients who are partially or fully edentulous have practiced poor oral
      hygiene. However, implants can benefit even those patients who are not ideal
      candidates. In cases of severe periodontal compromise, implants may enhance the
      survival of the natural teeth, minimize the difficulties of transition if
      additional tooth loss occurs, and also offer significant psychological benefit to
      the patient.

PMID- 1391920
TI  - Visible light-activated glass ionomer cement: use as liners/bases and
      restoratives.
AB  - Traditional glass ionomer cements were sensitive to moisture during the initial
      state and were subject to dehydration as the material began to harden.
      Preliminary findings from in vitro studies and clinical trials indicate that a
      new light activated glass ionomer cement exhibits high shear bond values, reduced
      microleakage and improved aesthetics.

PMID- 1391921
TI  - The interdental papilla pedicle graft: a simple and aesthetic approach to
      mucogingival correction.
AB  - The interdental papilla represents a potential source of donor tissue for
      effecting augmentation of the zone of gingiva. Root surfaces that have previously
      been exposed due to gingival recession also can be covered.

PMID- 1391922
TI  - Restoration of Class V abrasions with a new light-cured glass ionomer
      restorative.
AB  - The clinical performance of conventional glass ionomer materials have
      demonstrated clinical success in Class V restorations, but the physical
      properties and limited aesthetics of these materials have limited their
      widespread utilization. This article describes the clinical application of a new
      Type II light-cured glass ionomer restorative material, demonstrating improved
      physical properties and aesthetics.

PMID- 1391923
TI  - Direct proximal restoration of a permanent first molar: a window of opportunity.
AB  - Glass ionomer and composite resin direct application bonding has become an
      important part of modern restorative dentistry. This article describes the
      technique of glass ionomer/composite resin stratification restoration of the
      mesial surface of a permanent molar.

PMID- 1391924
TI  - The future of inlays and onlays.

PMID- 1391925
TI  - Direct oven-tempered hybrid composite-resin laminate veneers.
AB  - The difficulty in achieving optimal aesthetics of the single-tooth indirect
      laminate veneer has prompted the author to develop a direct technique for
      fabricating oven-tempered hybrid composite resin veneers. These restorations
      exhibit excellent physical properties, marginal integrity, and aesthetics.

PMID- 1391926
TI  - The bonded porcelain margin in porcelain-fused-to-metal prosthetics.
AB  - Progress in dentistry is often made when existing techniques and products are
      combined with new developments. For example, although porcelain has been used for
      decades and Buonocore reported on its use in 1955, only in early 1980 did bonded
      porcelain become popular. Today, we assume that porcelain facings and inlays are
      an integral part of dentistry.

PMID- 1391927
TI  - The plunging ball technique: Class II direct composite resins.
AB  - New polymer resin materials appear to be superior in wear resistance and may have
      less polymerization shrinkage than many other posterior restorative materials.
      With the use of the plunging ball technique, the ability to obtain tight contact
      and adequate contour results in fewer postoperative problems.

PMID- 1391928
TI  - Perception aesthetics and light-cured composites.
AB  - Perception aesthetics is the aspect of aesthetic dentistry concerned with
      patients' perception of their dental appearance. This article discusses how
      perception aesthetics can be affected by various factors, including the size,
      color, and shape of the teeth.

PMID- 1391929
TI  - Achieving anterior aesthetics with an anti-rotational abutment.
AB  - Single-tooth implants of various minerals and metals have been used, with some
      success, since ancient times. However, single-tooth implant survival was
      unpredictable until Branemark and his co-workers developed the theory and
      technique for obtaining a predictable direct bone to implant interface, which has
      been termed "osseointegration." Retrospective studies suggest excellent survival
      of single-tooth implants that predictably achieve this direct bone to implant
      interface. Case reports of single-tooth implants in the anterior and posterior
      areas of the jaws suggest the efficacy of this treatment, although scientific
      prospective studies evaluating the safety and efficacy of this treatment have
      only recently begun.

PMID- 1391930
TI  - The composite resin-amalgam window preparation.
AB  - Amalgam restorations with a very visible mesiofacial aspect can be aesthetically
      modified. Clinical experience has proven the amalgam window preparation to be an
      economical, expedient, and effective treatment approach when patients request
      tooth-colored fillings in posterior maxillary teeth.

PMID- 1391931
TI  - Some injustices in malpractice.

PMID- 1391932
TI  - Fabrication of an immediate aesthetic overdenture utilizing a resilient
      attachment.

PMID- 1391933
TI  - Conservative soft tissue management with the low-powered pulsed Nd:YAG dental
      laser.
AB  - Lasers can be operated in a continuous or pulsed mode, either in contact or out
      of contact with the target tissue. This article discusses laser systems and their
      resultant effects, and presents histologic findings and clinical examples.

PMID- 1391934
TI  - Progress in understanding the pathogenesis of the anemia of chronic disease.
AB  - Improved understanding of the inflammatory response and the identification and
      characterization of the specific cytokines involved, as well as improved
      understanding of erythropoiesis, and the availability of recombinant human growth
      factors such as EPO, have greatly enhanced our appreciation of the pathogenesis
      of ACD by allowing development of a number of informative models for studying
      this syndrome. It appears that a variety of cytokines are involved in all aspects
      of the pathogenesis of ACD, from the inhibition of erythroid progenitors and EPO
      production to impairment of iron release. A schematic of the contributions of
      some of these cytokines to the development of ACD is shown in Fig 6. The exact
      biochemical mechanisms by which these effects occur is still to be determined.
      The progress outlined in this report has allowed us to develop a more precise
      understanding of the pathogenesis of this common and important clinical syndrome.
      In 1983, Hansen subtitled a review of ACD "A Bag of Unsolved Questions." Although
      this description is still accurate, our understanding of ACD has now developed to
      the point where we can offer a more defined subtitle: "A Bag of Cytokines."

PMID- 1391935
TI  - Conditioning for allogeneic marrow transplantation in patients with
      lymphohematopoietic malignancies without the use of total body irradiation.

PMID- 1391936
TI  - Chromosome 11q23 translocations in both infant and adult acute leukemias are
      detected by in situ hybridization with a yeast artificial chromosome.
AB  - The yeast artificial chromosome (YAC-13HH4), which spans a 440-kb region of DNA
      just distal to the CD3 locus on chromosome 11 at band q23, has been used to
      characterize a range of chromosomal translocations in acute leukemias from both
      adults and infants. In situ hybridization was performed on metaphase cells from
      bone marrow of 17 leukemias and two cell lines with a variety of chromosome 11q23
      abnormalities. It was established that in infant leukemias the translocations
      t(11;19), t(4;11), and t(5;11) had occurred in the region defined by YAC 13HH4.
      Additionally, the translocations t(4;11), t(6;11), t(9;11), t(X;11), and t(10;11)
      in other leukemias were found to disrupt the same region of chromosome 11q23,
      although an exception was found in one t(6;11) translocation for which the
      breakpoint was distal to the YAC. One patient had a t(9;11) translocation in a
      therapy-related leukemia, suggesting that this class of etoposide-related
      malignancy has similar breakpoints to those occurring in de novo leukemias. An
      example of a lymphoma-derived translocation t(4;11) was shown to involve a
      deletion of the region defined by YAC 13HH4. A leukemia with a deletion on
      chromosome 11 (q23-q25) was also studied and it was shown that the YAC sequence
      was unaffected. It was concluded that, with a few exceptions, the translocations
      at 11q23 in a wide range of acute infant and adult leukemias occur in a common
      region and may result from a common underlying mechanism.

PMID- 1391937
TI  - Low-risk intensive therapy for multiple myeloma with combined autologous bone
      marrow and blood stem cell support.
AB  - To improve the safety of autotransplantation for myeloma, peripheral blood stem
      cell (PBSC) collection was attempted in 75 previously treated patients after the
      administration of high-dose cyclophosphamide (HD-CTX; 6 g/m2) with or without
      granulocyte-macrophage colony-stimulating factor (GM-CSF). Sixty patients
      subsequently received melphalan 200 mg/m2 (57 patients) or melphalan 140 mg/m2
      and total body irradiation (850 cGy) (3 patients) supported by both autologous
      bone marrow and PBSC; 38 patients received GM-CSF posttransplantation. Among 72
      patients undergoing PBSC apheresis, "good" mobilization (greater than 50 colony
      forming units granulocyte-macrophage [CFU-GM] per 10(5) mononuclear cells) was
      achieved when prior chemotherapy did not exceed 1 year and when GM-CSF was used
      post-HD-CTX; similarly, rapid platelet recovery to 50,000/microL within 2 weeks
      was associated with "good" PBSC mobilization. These same variables also predicted
      for rapid engraftment after autotransplantation, so that hematologic recovery
      (granulocytes greater than 500/microL and platelets greater than 50,000/microL)
      proceeded within 2 weeks among the 37 patients with "good" PBSC collection. As a
      result of rapid neutrophil recovery (greater than 500/microL) within a median of
      2 weeks, infectious complications both post-HD-CTX and posttransplant were
      readily manageable, resulting in only one treatment-related death post-HD-CTX.
      The cumulative response rate (greater than or equal to 75% cytoreduction) for all
      75 patients was 68%, with 12-month event-free and overall survival projections of
      about 85%. Using both bone marrow and PBSC together with GM-CSF, autotransplants
      are safe and appear effective in myeloma, especially when prior therapy had been
      limited to less than 1 year. More than 80% of transplanted patients achieved
      complete hematologic recovery within a median of 1 month posttransplant
      (granulocytes greater than 1,500/microL; platelets greater than 100,000/microL;
      hemoglobin greater than 10 g%), thus providing sufficient hematopoietic reserve
      for further chemotherapy in the event of posttransplant relapse.

PMID- 1391939
TI  - The role of macrophages in the regulation of erythroid colony growth in vitro.
AB  - Depletion of macrophages from murine marrow by the use of a monoclonal anti
      macrophage antibody resulted in a significant increase in the number of erythroid
      burst forming units (BFU-E). This increase could be neutralized by the addition
      back to culture of macrophages or macrophage conditioned medium indicating that
      the suppression was mediated by soluble factors. To further characterize this
      effect, the addition to culture, either alone or in combination, of interleukin-1
      alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha), and granulocyte
      macrophage colony-stimulating factor (GM-CSF) on the growth of BFU-E and the
      colony-forming unit granulocyte-macrophage (CFU-GM) was examined in macrophage
      containing and macrophage-depleted cultures. The addition of IL-1 alpha to
      culture stimulated the release of both TNF alpha and GM-CSF and acted
      synergistically with both cytokines, resulting in a dose-dependent suppression of
      BFU-E and stimulation of CFU-GM growth. The increase in CFU-GM caused by the
      addition of IL-1 alpha was mediated by GM-CSF but not by TNF alpha as the
      increase was prevented by the addition of a monoclonal anti-GM-CSF antibody but
      not by anti-TNF alpha. When either TNF alpha or GM-CSF was neutralized by
      monoclonal antibodies the addition of IL-1 alpha resulted in a significant
      increase in BFU-E growth. The addition of GM-CSF to culture caused a dose
      dependent suppression of BFU-E that was mediated by TNF alpha, as colony number
      was not reduced when GM-CSF and a monoclonal anti-TNF alpha antibody were
      simultaneously added to culture. TNF alpha-induced suppression of BFU-E only
      occurred in the presence of macrophages. In macrophage-depleted cultures, a dose
      dependent suppression of BFU-E could be induced if subinhibitory concentrations
      of IL-1 alpha or GM-CSF were simultaneously added with increasing concentrations
      of TNF alpha. The effects of IL-1 alpha or GM-CSF and TNF alpha were markedly
      synergistic so that the doses required to induce suppression when added
      simultaneously was only 10% of that required when either were added to culture
      alone. Suppression of BFU-E by GM-CSF or the combined addition of GM-CSF and TNF
      alpha did not require IL-1 alpha because inhibition was not neutralized by the
      addition of anti-IL-1 alpha antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1391938
TI  - Enhanced marrow recovery by short preincubation of marrow allografts with human
      recombinant interleukin-3 and granulocyte-macrophage colony-stimulating factor.
AB  - We studied an alternative method of using hematopoietic growth factors (HGFs) to
      enhance hematopoietic recovery in patients undergoing bone marrow transplantation
      (BMT), by short in vitro preincubation. Twenty consecutive patients with leukemia
      received T-cell-depleted allografts using Campath-1G. Two thirds of the marrow
      was infused on the scheduled day of transplant and one third of the marrow
      following preincubation with granulocyte-macrophage colony-stimulating factor (GM
      CSF) and interleukin-3 (IL-3) on day 4. Engraftment parameters and duration of
      hospitalization were compared by actuarial analysis to those of 40 historical
      controls. Patients receiving the incubated boost had significantly faster
      platelet recovery (P = .017) and shorter hospitalization period (P = .001) when
      compared with the control subjects. Platelet count reached greater than 25 x
      10(9)/L on day 17 (median) in the study group and on day 23 in the controls. The
      median duration of hospitalization was 20 and 36 days, respectively. In the early
      posttransplantation follow-up, two of four patients in the study group died as a
      result of graft rejection, while all 13 deaths in the control group resulted from
      complications associated with marrow suppression. We suggest that pretransplant
      in vitro activation of bone marrow cells with IL-3 and GM-CSF may prove to be an
      efficient method for enhancing marrow recovery after BMT.

PMID- 1391940
TI  - Identification and characterization of osteoclast progenitors by clonal analysis
      of hematopoietic cells.
AB  - We have identified a distinct population of colony-forming cells that give rise
      to mononuclear cells expressing an enzyme marker and other features of the
      osteoclast in bone marrow cultures stimulated by conditioned medium of a murine
      tumor cell line. These colony-forming cells were defined as osteoclast colony
      forming units (CFU-O). The tumor cell-derived activity was recently isolated and
      was named osteoclast colony-stimulating factor (O-CSF). To understand the
      development of osteoclast progenitors and to clarify the relationship of
      osteoclast progenitors to other hematopoietic progenitors, we examined CFU-O in
      hematopoietic tissues obtained from normal adult mice, mouse fetuses, and mice
      with 5-fluorouracil (5FU) treatment. CFU-O were present in the adult mouse bone
      marrow, adherent cell-depleted marrow, in the spleen, and in the day 14 fetal
      liver, with an incidence similar to other hematopoietic progenitors. The culture
      period required for the development of CFU-O-derived colonies in vitro and the
      manner in which CFU-O responded to 5FU suggested that CFU-O belonged to a
      relatively primitive progenitor population; they are clearly more immature than
      macrophage progenitors that respond to macrophage-CSF, but more mature than
      multilineage progenitors that respond to stem cell factor. Our studies have
      defined and characterized an osteoclast progenitor and distinguished it from
      other hematopoietic progenitors for the first time.

PMID- 1391941
TI  - CD4 is expressed on murine pluripotent hematopoietic stem cells.
AB  - We show here for the first time that pluripotent hematopoietic stem cells express
      the CD4 antigen. CD4+ cells isolated from mouse marrow repopulated all
      hematopoietic lineages in both the long-term repopulation assay and the
      competitive repopulation assay. This finding indicates that the CD4+ population
      contains primitive stem cells with extensive repopulation capacity.
      Interestingly, the CD4- population had significant life-sparing activity, even
      though this population was depleted of long-term repopulating stem cells when
      compared with CD4+ cells. The majority of the cells that respond to the stroma in
      Whitlock-Witte cultures with B-cell differentiation were recovered in the CD4-
      population. Thus, this bone marrow (BM)-derived B-cell precursor lacks CD4, which
      is in contrast to myeloid precursors and thymus-derived lymphoid precursors that
      reportedly express CD4. We show further that the CD4 molecule expressed on BM
      cells is similar in molecular weight and epitope makeup to the CD4 antigen found
      on thymocytes. Detection of CD4 on BM cells is dependent on using high
      concentrations of antibodies. Thus, it is not surprising that expression of CD4
      on pluripotent stem cells has been missed previously. Taken together, our data
      suggest that the CD4 molecule may play an important role in lineage definition in
      early hematopoietic differentiation.

PMID- 1391942
TI  - A novel temporal expression pattern of three C/EBP family members in
      differentiating myelomonocytic cells.
AB  - Members of the CCAAT/enhancer binding protein (C/EBP) family have been shown to
      regulate the terminal differentiation of adipocytes and hepatocytes. In these
      cell lineages, high levels of C/EBP alpha are found only in mature, nondividing
      cells. Using Western blotting and immunohistochemical staining, we have
      determined the temporal order of expression for C/EBP alpha, C/EBP beta, and
      C/EBP delta in differentiating myelomonocytic marrow cells. These studies show a
      unique temporal pattern of C/EBP isoform expression in the myeloid lineage. In
      particular, C/EBP alpha expression is very high in proliferative myelomonocytic
      cells, and diminishes during phenotypic maturation. While we have detected C/EBP
      alpha, C/EBP beta, and C/EBP delta in multiple myeloid leukemia cell lines, and
      C/EBP alpha in normal myeloid cells and in de novo human myeloid leukemias, we
      have not detected these C/EBP isoforms in either erythroid or lymphoid cells.
      Finally, we show that C/EBP alpha, C/EBP beta, and C/EBP delta protein and
      messenger RNA levels correlate in maturing granulocytic cells. The formation of
      tissue-specific combinations of C/EBP homodimers and heterodimers may allow this
      family of transcription factors to regulate different sets of genes in
      adipocytes, hepatocytes, and myelomonocytes.

PMID- 1391943
TI  - Evidence that postoperative fibrinolytic shutdown is mediated by plasma factors
      that stimulate endothelial cell type I plasminogen activator inhibitor
      biosynthesis.
AB  - Postoperative fibrinolytic shutdown has been attributed to an increase in plasma
      levels of type I plasminogen activator inhibitor (PAI-1) activity and may
      contribute to postoperative venous thrombosis. The purpose of this study was to
      determine whether the postoperative increase in PAI-1 is contributed to by a
      plasma mediator(s) that stimulates PAI-1 synthesis and secretion by vascular
      endothelium. Plasma samples collected from patients (N = 11) before and after
      surgery for total hip replacement were (1) assayed for endogenous plasma PAI-1
      antigen and activity, and (2) incubated with cultured human umbilical vein
      endothelial cells (HUVECs) and PAI-1 antigen and activity measured in the
      conditioned medium (CM). Eighteen hours after surgery, endogenous plasma levels
      of PAI-1 antigen and activity were increased by 225% (P = .003) and 190% (P =
      .04), respectively over the preoperative values. In addition, compared with
      preoperative plasma, postoperative plasma increased HUVEC secretion of PAI-1
      antigen and activity by 99% (P = .001) and 66% (P = .002), respectively. This
      increase in HUVEC PAI-1 secretion reflects an increase in PAI-1 mRNA expression
      and protein biosynthesis as confirmed by metabolic radiolabeling,
      immunoprecipitation, and Northern blot analysis. Ultra-filtration experiments
      indicate that the postoperative plasma mediator(s) that stimulates HUVEC PAI-1
      biosynthesis is in a molecular weight (MW) range of approximately 30 to 100 Kd.
      Heat treatment (56 degrees C; 30 minutes) of postoperative plasma abolished the
      induction of HUVEC PAI-1 production. Enzyme-linked immunosorbent assay and
      immunoneutralization experiments indicate that tumor necrosis factor-alpha (TNF
      alpha) and interleukin-1 alpha (IL-1 alpha) do not contribute to the
      postoperative plasma effect on HUVEC PAI-1 synthesis. These observations
      demonstrate that postoperative patient plasma contains a factor(s) that may
      stimulate endothelial cell PAI-1 biosynthesis in vivo and thus mediate
      postoperative fibrinolytic shut-down.

PMID- 1391944
TI  - Heterogeneous immunophenotype of granular lymphocyte expansions: differential
      expression of the CD8 alpha and CD8 beta chains.
AB  - In this study, we have evaluated 14 large granular lymphocyte (LGL) expansions,
      11 of which were CD8+. Analysis of the membrane expression of the alpha and beta
      chains of the CD8 antigen, using specific monoclonal antibodies (MoAbs), has
      shown that LGL expansions with the CD3+, CD4+, CD8+, CD57+ T-cell receptor (TcR)
      alpha beta phenotype bear the CD8 alpha/alpha isoform, while the CD3+, CD4-,
      CD8+, CD57+ TcR alpha beta samples were positive for both the CD8 alpha and CD8
      beta chains. These data were confirmed also by messenger RNA analysis. One
      additional case, with a peculiar phenotype (CD3-, CD2-, CD4-, CD8+, CD57-) and a
      germline configuration of the TcR beta and gamma chain genes, expressed only the
      CD8 alpha chain. After additional phenotypic analysis with a wider panel of
      MoAbs, it was found that the beta chain of the interleukin-2 receptor was
      constitutively expressed on the majority of the samples tested, and that most of
      the monoclonal samples coexpressed CD45RA/R0 antigens. Using MoAbs directed
      against the variable regions of the TcR beta chain, we could show a preferential
      V beta region restriction in the CD8+ monoclonal cases. This more extensive
      characterization of CD8+ LGL expansions has further documented the marked
      heterogeneity within this rare condition and allowed a better phenotypic
      dissection between the monoclonal and polyclonal cases.

PMID- 1391945
TI  - Detection and quantitation of malignant cells in the peripheral blood of multiple
      myeloma patients.
AB  - One of the distinguishing features of multiple myeloma (MM) is the proliferation
      of plasma cells that home to the bone marrow (BM). However, there still remains
      some uncertainty concerning the presence of related malignant cells in the
      peripheral blood of myeloma patients. Using consensus oligonucleotide primers, we
      amplified the third complementary determining region (CDR3) of rearranged
      immunoglobulin heavy chain alleles from MM marrow samples by polymerase chain
      reaction (PCR). From the sequences of the products, we derived allele-specific
      oligonucleotides (ASO), and these were used in subsequent amplification reactions
      to detect malignant clones in the peripheral blood of myeloma patients. This
      method is highly specific and sensitive to 1 malignant cell in the background of
      10(5) normal cells. Using this method we detected circulating malignant cells in
      13 of 14 previously untreated MM patients. Furthermore, by applying ASO-PCR to
      artificial titrations of initial BM DNA sample into normal peripheral blood
      lymphocyte (PBL) DNA we were able to generate standard curves and quantitate the
      amount of tumor in the patient PBL. We observed a wide variation in the amount of
      circulating tumor between patients. In addition, we found that the incidence of
      circulating tumor cells was independent of BM tumor burden and stage of disease.
      The detection and quantitation of circulating tumor cells in the PBL of MM
      patients may offer an alternative assessment of the disease and may be an
      important consideration in the use of peripheral stem cells in bone marrow
      transplantation.

PMID- 1391946
TI  - Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation
      of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation
      gene, runt.
AB  - We have developed a restriction map of the chromosome 21 breakpoint region
      involved in t(8;21)(q22;q22.3) acute myelogenous leukemia (AML) and have isolated
      a genomic junction clone containing chromosome 8 and 21 material. Using probes
      from these regions, rearrangements have been identified in each of nine cases of
      t(8;21) AML examined. In addition, we have isolated cDNA clones from a t(8;21)
      AML cDNA library that contain fused sequences from chromosome 8 and 21. The
      chromosome 8 component, referred to as ETO (for eight twenty-one), is encoded
      over a large genomic region, as suggested by the analysis of corresponding yeast
      artificial chromosomes (YACs). The DNA sequence of the chromosome 21 portion of
      the fusion transcript is derived from the normal AML1 gene. A striking similarity
      (67% identity over 387 bp, with a corresponding 69% amino acid identity) was
      detected between AML1 and the Drosophila segmentation gene, runt. The critical
      consequence of the translocation is the juxtaposition of 5' sequences of AML1 to
      3' sequences of ETO, oriented telomere to centromere on the der(8) chromosome.

PMID- 1391947
TI  - Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow
      transplantation and prophylaxis with cyclosporine and methotrexate.
AB  - Previous studies of risk factors for acute graft-versus-host disease (GVHD)
      involved patients receiving predominantly single-agent prophylaxis. Therefore, a
      retrospective analysis was performed on 446 patients, from a single institution,
      who received transplants of marrow from HLA-identical siblings and the
      combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk
      factors for acute GVHD associated with this more effective form of GVHD
      prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD
      were 35% and 16%, respectively. Increased clinical grades of acute GVHD in
      patients without advanced malignant disease were associated with a decreased
      survival. In a multivariate Cox regression analysis, risk factors associated with
      the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P =
      .001), increased dose of total body irradiation (TBI) (P = .001), and reduction
      to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The
      multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group
      defined as having advanced malignant disease at transplant; however, this
      difference failed to reach conventional levels of statistical significance (P =
      .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients,
      respectively, primarily because of renal or hepatic dysfunction. The periods of
      increased risk for the onset of acute GVHD were up to 1 week after a reduction of
      MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades
      II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was
      associated with increased patient age of 40 years or greater (P = .05) and dose
      reductions of CSP (P = .008). Serologic status of patient and donor for
      cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a
      laminar air flow room during marrow transplantation, all previously identified as
      risk factors for acute GVHD, were not confirmed as risk factors in this study
      population. The toxicity of MTX and CSP and the development of acute GVHD from
      inadequate immunosuppression because of dose reduction warrants further trials
      with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD
      should be considered in clinical management and in the design of clinical trials.

PMID- 1391949
TI  - No correlation between the type of bcr-abl hybrid messenger RNA and platelet
      counts in chronic myelogenous leukemia.

PMID- 1391948
TI  - Anti-CD3 + interleukin-2 stimulation of marrow and blood: comparison of
      proliferation and cytotoxicity.
AB  - The proliferation and in vitro cytolytic activity of interleukin-2 (IL-2)
      activated and anti-CD3 + IL-2-stimulated marrow mononuclear cells (MMC) and
      peripheral blood mononuclear cells (PBMC) were studied. Samples from 8 normal
      donors, 15 patients with acute lymphoblastic leukemia (ALL), and 7 patients with
      non-Hodgkin's lymphoma (NHL) in remission were cultured in IL-2 (100 U/mL) or IL
      2 (100 U/mL) plus anti-CD3 (10 ng/mL). MMC as well as PBMC samples demonstrated
      significant synergy between IL-2 and anti-CD3 in the promotion of proliferation
      as measured by 3H thymidine incorporation on day 5 (P less than .001) or fold
      increase in cell number on day 14. Cryopreserved marrow specimens had equally
      rapid proliferation as fresh MMC when cultured in the presence of anti-CD3 + IL
      2. Anti-CD3 concentrations of 3, 11, 33, and 100 ng/mL augmented proliferation
      similarly in the presence of IL-2 (0.1 to 100 U/mL). Mean fold increases in cell
      number of both marrow- and blood-derived cultures after 14 days were
      significantly higher for anti-CD3 + IL-2-stimulated cultures compared with
      cultures stimulated with IL-2 only (50- to 200-fold increase in cell number; P =
      .01). Comparison of remission MMC and PBMC from ALL and NHL patients with normal
      controls showed equivalent growth rates of activated cultures at 7, 14, and 21
      days. Marrow purging with immunotoxin anti-CD19 pokeweed antiviral protein plus
      4HC had no significant effect on proliferation of anti-CD3 + IL-2-stimulated MMC
      cultures in patients with ALL. Cytolytic activity of IL-2- and IL-2 + anti-CD3
      activated PBMC and MMC cultures was assessed in 51Cr release assays using K562
      (natural killer ([NK]-sensitive), Daudi (Burkitt's lymphoma-, NK-resistant), and
      Nalm-6 (ALL-, lymphokine-activated killer [LAK]-resistant) cell lines and
      cryopreserved ALL blasts. Cytolytic activity on a per-cell basis (percent
      cytotoxicity at an effector:target ratio of 30:1) was similar in IL-2-activated
      PBMC- and MMC-derived cultures from ALL patients. MMC activated with anti-CD3
      plus IL-2 killed Daudi significantly less well than IL-2-activated cultures on
      days 12 and 19 (P = .03); no significant differences were observed in lysis of
      LAK-resistant Nalm-6 or cryopreserved ALL blast targets. Dose response of anti
      CD3 augmentation of Daudi and Nalm-6 killing was different in IL-2- and IL-2 +
      anti-CD3-stimulated cultures.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1391950
TI  - Wolf in wolf's clothing: is it time to raise the bounty on the passenger
      leukocyte?

PMID- 1391951
TI  - Red blood cell glycophorins.

PMID- 1391952
TI  - Thrombotic microangiopathies in the 1980s: clinical features, response to
      treatment, and the impact of the human immunodeficiency virus epidemic.
AB  - We reviewed the medical records of 44 adults with 50 consecutive episodes of
      thrombotic thrombocytopenia purpura (TTP) or hemolytic uremic syndrome (HUS) seen
      at the University of California, San Francisco affiliated hospitals during the
      past decade. Patients were treated according to a uniform plan in which initial
      therapy included daily large volume plasmapheresis using fresh frozen plasma.
      Patients not responding completely to initial therapy were treated with a salvage
      regimen including splenectomy, dextran, and corticosteroids. At the time of
      diagnosis, the lactate dehydrogenase (LDH) was elevated in 98% of cases, with a
      median value of 1,208 U/L. Other clinical features were present inconsistently,
      and only 34% of "TTP" episodes involved the classic pentad of hemolytic anemia,
      thrombocytopenia, neurologic disorders, noninfectious fever, and renal
      impairment. Primary treatment with plasma exchange produced complete remission in
      56% (27 of 48) of the episodes. Previously splenectomized patients uniformly
      responded to plasma therapy (12 of 12). In patients not responding completely to
      primary therapy, salvage splenectomy produced complete responses in 81% (13 of
      16) of the cases. The pattern of clinical response to therapy was consistent,
      with initial resolution of neurologic dysfunction (median, 3 days) followed by
      normalization of LDH levels (5 days) and platelet count (7 days). Normalization
      of renal function occurred significantly later (15 days). Although short-term
      responses to plasma therapy in human immunodeficiency virus (HIV)-seropositive
      patients did not differ from other patients, no HIV-positive patient survived
      more than 2 years from diagnosis of thrombotic microangiopathy (TMA). We conclude
      that the diagnosis of TMA requires a high degree of clinical suspicion and that
      the diagnostic criteria should consist of microangiopathic hemolytic anemia,
      thrombocytopenia, and an elevated LDH. Initial therapy with plasma exchange leads
      to disease control in the majority of cases, but an optimal treatment strategy
      requires the use of alternative methods if initial remission is transient or not
      achieved. Salvage therapy with splenectomy, steroids, and dextran is highly
      effective in this setting.

PMID- 1391954
TI  - Fibrinogen Marburg: a homozygous case of dysfibrinogenemia, lacking amino acids A
      alpha 461-610 (Lys 461 AAA-->stop TAA).
AB  - In the A alpha-chain gene coding for an abnormal fibrinogen (fibrinogen Marburg)
      we identified a single base substitution (A-->T) that changes the codon A alpha
      461 AAA (Lys) to TAA (Stop). The propositus was found to be homozygous for the
      mutation, whereas the father and five siblings were heterozygous, and three other
      siblings contained only the normal sequence. The stop codon at position 461
      results in the deletion of the carboxyl-terminal segment A alpha 461-610.
      Purified fibrinogen Marburg contained an A alpha-chain with a relative molecular
      weight of approximately 47,000. The FpA release by thrombin was not affected by
      this deletion, whereas the fibrin polymerization was strongly decreased. The
      binding of endothelial cells to immobilized fibrinogen Marburg was almost
      completely abolished compared with normal fibrinogen. Fibrinogen Marburg
      contained a substantial amount of albumin linked to the fibrinogen molecule by
      disulfide bonds, and these fibrinogen-albumin complexes were also present in
      plasma. The plasma fibrinogen concentration of the propositus was measured by
      three different methods: a functional method (< 0.25 mg/mL), an immunologic
      method using polyclonal antibodies (0.6 mg/mL), and an immunologic method based
      on two monoclonal antibodies specific for the amino-terminus and carboxyl
      terminus of the A alpha-chain (< 0.05 mg/mL). Using the two immunologic methods,
      it appeared that only 10% to 15% of the plasma fibrinogen of the heterozygous
      siblings was abnormal.

PMID- 1391953
TI  - Differentiation and erythropoietin receptor gene expression in human erythroid
      progenitor cells.
AB  - Partially purified human burst-forming unit-erythroid (BFU-E) cells from
      peripheral blood were cultured for 6 to 8 days to obtain colony-forming unit
      erythroid (CFU-E) cells. When these BFU-E-derived CFU-E were further purified and
      recultured in liquid suspension cultures with erythropoietin (EPO), they matured
      and differentiated into reticulocytes in vitro. A maximum rate of hemoglobin
      synthesis was observed at day 10 of cumulative culture time by measuring 59Fe
      incorporation into heme. Withdrawal of EPO from erythroblast cultures at various
      times during development showed that between day 10 and day 11 (when the majority
      of the cells are in the polychromatic erythroblast stage), these cells became
      independent of EPO. The timing of the disappearance of the EPO requirement in
      these cells coincided with the marked decline in proliferation. Measurement of
      EPO receptor messenger RNA (mRNA) levels by Northern analysis showed that there
      is a slight decline during the day 8 to day 10 time period, followed by a rapid
      decline between days 10 and 14. Binding of 125I-EPO to erythroblasts also showed
      a steady decline of the cell surface binding during maturation and terminal
      differentiation. The half-life of the human EPO receptor was 90 minutes in the
      presence of the transcriptional inhibitor actinomycin D and the half-life
      measured at two different times during the 8- to 14-day culture period remained
      constant. These results indicate that human EPO receptor mRNA must be transcribed
      continuously to maintain the levels seen by Northern analysis. The human cell
      system described here is well suited for the study of a wide variety of
      biochemical events during late erythroid differentiation.

PMID- 1391955
TI  - Generation of vasoactive peptide bradykinin from human umbilical vein endothelium
      bound high molecular weight kininogen by plasma kallikrein.
AB  - High molecular weight kininogen (HK) is a multifunctional plasma glycoprotein
      that occupies a critical position in pathways that link inflammation and
      coagulation. It is an inhibitor of sulfhydryl proteases and has procoagulant
      properties. It is also a source of the vasoactive peptide bradykinin (BK). It has
      been previously shown that HK binds to human umbilical vein endothelial cells
      (HUVEC) in culture. We have further characterized that interaction herein.
      Immunohistochemical experiments have indicated that when freshly obtained
      umbilical vein segments were treated with HK, washed, and probed with anti-HK
      antibodies, HK was localized on the endothelium. We next determined whether HUVEC
      bound HK can be cleaved by plasma kallikrein to release BK. Cultured HUVEC were
      incubated with unlabeled HK for varying times, washed, and the kinetics of BK
      release by plasma kallikrein were assayed by radioimmunoassay. Results indicated
      that kallikrein released BK from HUVEC in proportion to the initial amount of
      bound HK. No release of BK occurred in the absence of kallikrein. Also, there was
      no BK release upon kallikrein treatment of the HUVEC not treated with exogenous
      HK. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography
      of HUVEC-bound 125I-HK indicated that addition of kallikrein resulted in cleavage
      of HK, thus corroborating the BK release experiments. Comparison of cleavage
      patterns has also indicated that cell-bound HK is slightly less susceptible to
      digestion by kallikrein than free HK. Therefore, our data suggest that human HK
      can bind to vascular endothelium in situ and that plasma kallikrein can recognize
      endothelial-bound HK as a substrate and liberate the vasoactive peptide BK.

PMID- 1391956
TI  - Factor Xa interacts with two sites on monocytes with different functional
      activities.
AB  - Studies were performed to elucidate the functional significance of factor Xa
      interactions at the monocyte membrane in the presence and absence of factor Va,
      with respect to prothrombin and factor IX cleavage. Factor Xa-catalyzed
      prothrombin activation at the monocyte surface was absolutely dependent on the
      addition of factor Va, indicating that thrombin was generated solely by a
      membrane-bound complex of factors Va and Xa. In contrast, in the absence of added
      factor Va, factor Xa bound to monocytes catalyzed the cleavage of factor IX to
      the nonenzymatic intermediate factor IX alpha through a reaction that was
      dependent on both monocyte and factor Xa concentration. At limiting factor Xa
      concentration, added factor Va inhibited the factor Xa-catalyzed cleavage of
      factor IX, suggesting that a monocyte-bound complex of factors Va and Xa did not
      recognize factor IX as a substrate. These combined data suggest that factor Xa
      interacts with the monocyte through two sites which can be distinguished by their
      requirement for added factor Va and their expression of different functional
      activities. Both functional sites could be distinguished also by their
      differential susceptibility to inhibition by a monoclonal antibody directed
      against the light chain of factor Va (alpha-HFV1). At the monocyte surface, the
      factor Va/Xa-catalyzed activation of prothrombin was maximally inhibited with
      0.25 mumol/L alpha-HFV1, whereas 1.0 mumol/L alpha-HFV1 was required to effect
      50% inhibition of the factor Xa-catalyzed cleavage of factor IX. The ability of
      factor Va to modulate factor Xa substrate specificity was investigated further.
      Factor Xa bound to thrombin-activated platelets either through platelet-released
      factor Va or added factor Va did not cleave factor IX. Consistent with this
      result, a plasma concentration of factor IX had no effect on thrombin generation
      catalyzed by a platelet-bound complex of factors Va and Xa. In marked contrast,
      factor Xa bound to phospholipid vesicles either independently or in complex with
      factor Va catalyzed factor IX cleavage with equal efficiency. These combined data
      indicate that factor Va bound to cell surfaces modulates factor Xa substrate
      specificity, whereas no discriminatory effect is conferred by factor Va bound to
      phospholipid vesicles. Thus, by providing two distinct sites at its membrane
      surface, the monocyte modulates factor Xa binding and the functional activity
      expressed by the bound enzyme, depending on the availability of factor Va.

PMID- 1391957
TI  - Maturation of the hemostatic system during childhood.
AB  - The hemostatic system is assumed to be similar in children and adults and
      reference ranges established for adults are commonly used to evaluate children
      suspected of having congenital or acquired hemostatic problems. However, we know
      that the hemostatic system is not fully mature by 6 months of age and
      comprehensive studies of healthy older children have not been published.
      Therefore, we conducted a prospective cohort study of the hemostatic system in
      healthy children having minor, elective day surgery. After obtaining informed
      consent, a 3-mL blood sample was obtained at the time routine preoperative blood
      work was drawn. The plasma was fractioned and stored at -70 degrees C for batch
      assaying. We measured the concentration of 33 components of the hemostatic system
      (functional and immunologic assays) and the bleeding time (automated pediatric
      device) in 246 children aged 1 to 16 inclusive (a minimum of four subjects at
      each age). Eleven components of hemostasis (fibrinogen, prekallikrein, high
      molecular weight kininogen, factors VIII and XIII, antithrombin III [ATIII],
      heparin cofactor II [HCII], alpha 1-antitrypsin [alpha 1AT], protein S,
      plasminogen, alpha 2-antiplasmin [alpha 2AP]) had mean values and ranges of
      normal that were similar to adults. Mean values of seven coagulants (II, V, VII,
      IX, X, XI, XII) were significantly lower than adult values and varied with age.
      Values for three inhibitors, alpha 2-macroglobulin (alpha 2M), protein C, and
      protein C1-inhibitor (C1-Inh) also differed from adults. Alpha 2M and C1-Inh
      inhibitor levels were elevated throughout childhood, whereas protein C levels
      were low, with a lower limit of normal of 0.40 U/mL until the age of 11. Finally,
      the upper limit of normal for the bleeding time was longer in children during the
      first 10 years of life, but decreased to adult values in the teenage years. In
      summary, there are important physiologic differences in the hemostatic system in
      children compared with adults. The decreased levels of several critical
      coagulants and increased levels of alpha 2M may contribute in part to the lower
      risk of thrombotic events in childhood. Age-matched controls should be used for
      evaluation of the hemostatic system in children with suspected congenital or
      acquired defects.

PMID- 1391958
TI  - Antiplatelet drugs and generation of thrombin in clotting blood.
AB  - Platelets participate in formation of thrombin through secretion of coagulation
      factors and by providing a catalytic surface on which prothrombinase complex is
      assembled. We studied the effects of four antiplatelet drugs on thrombin
      formation in healthy volunteers. Thrombin generation was monitored both in vitro-
      in recalcified plasma--and ex vivo--in blood emerging from a standardized skin
      microvasculature injury, which also served to determine bleeding time. A
      mathematical model has been developed to describe the latter reaction. It is
      based on estimation of the rate of increase in fibrinopeptide A (FPA), a specific
      marker of thrombin activity, in blood emerging from skin incisions. Two hours
      after the ingestion of 500 mg of aspirin, thrombin formation became significantly
      impaired both in vitro and ex vivo. In contrast, 2 hours after the oral
      administration of placebo, indomethacin 50 mg, or OKY-046 (a thromboxane synthase
      inhibitor) 400 mg, thrombinogenesis remained unaltered. Ticlopidine, studied
      either 3 hours after 500 mg oral administration, or after 5 days of intake at a
      daily dose of 500 mg, had no effect on thrombin generation. Thus, aspirin,
      contrary to other antiplatelet drugs, depresses thrombin formation in clotting
      blood, a phenomenon that might be of clinical relevance. It is suggested that
      aspirin exerts this effect by acetylating prothrombin and/or macromolecules of
      platelet membrane.

PMID- 1391959
TI  - Detection of bcl-2 protein and bcl-2 messenger RNA in normal and neoplastic
      lymphoid tissues by immunohistochemistry and in situ hybridization.
AB  - bcl-2 protein has been detected in surgical specimens and cultured permanent cell
      lines of non-Hodgkin's lymphomas and leukemias using enzyme immunohistochemistry
      and immunofluorescence with anti-bcl-2 monoclonal antibodies. Of 40 surgical
      specimens, bcl-2 protein was expressed in 50% of B-cell and 41% of T-cell
      lymphomas, both with and without the bcl-2 gene rearrangement. In investigations
      of 38 hematopoietic cell lines, bcl-2 protein was detected not only in lymphoid
      cell lines but also in myeloid cell lines. In situ hybridization and
      immunohistochemical analysis of reactive lymph nodes showed that lymphocytes in
      mantle zones and paracortical areas expressed bcl-2 protein consistent with the
      messenger RNA distribution and that germinal center cells showed abundant bcl-2
      transcript, despite the absence of detectable bcl-2 protein. These results
      suggest that bcl-2 protein is broadly expressed in various hematopoietic
      neoplasms not restricted in t(14; 18) lymphomas and that germinal center cells
      may be involved in some arrest of bcl-2 protein expression at the
      posttranscriptional level.

PMID- 1391960
TI  - Identification and expression of a common missense mutation (L302P) in the acid
      sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients.
AB  - Types A and B Niemann-Pick disease (NPD) result from the deficient activity of
      acid sphingomyelinase (ASM; E.C. 3.1.4.12) and the resultant lysosomal
      accumulation of sphingomyelin. Type A disease is a fatal, neurodegenerative
      disorder of infancy, whereas type B disease has no neurologic manifestations and
      is characterized primarily by reticuloendothelial involvement and survival into
      adulthood. Both disorders occur more frequently among individuals of Ashkenazi
      Jewish ancestry than in the general population. Recently, a missense mutation in
      the ASM gene (designated R496L) was detected in more than 30% of the ASM alleles
      from Ashkenazi Jewish type A NPD patients. We report a second, common mutation
      that resulted from a T to C transition at nucleotide 905 and predicted a leucine
      to proline substitution at ASM codon 302 (designated L302P). Notably, the L302P
      mutation occurred in 23.5% (8 of 34) of the Ashkenazi Jewish type A NPD alleles
      studied. In contrast, it was not found in any of the ASM alleles from non-Jewish
      type A patients, in 36 alleles from type B patients, or in 100 ASM alleles from
      normal Ashkenazi Jewish individuals. To confirm the authenticities of the L302P
      and R496L mutations, each nucleotide change was separately introduced into the
      full-length ASM cDNA by site-directed mutagenesis and transiently expressed in
      COS-1 cells. Neither mutation expressed ASM catalytic activity, consistent with
      the type A phenotype of homoallelic patients. The identification of the L302P
      mutation should further facilitate molecular carrier detection for NPD in the
      Ashkenazi Jewish population, particularly because the L302P mutation can be
      easily detected using the restriction enzyme, AlwNl.

PMID- 1391961
TI  - Rapid diagnosis of beta-thalassemia mutations in Chinese by naturally and
      amplified created restriction sites.
AB  - We developed a rapid and simple method to diagnose the molecular defects of beta
      thalassemia in Chinese patients. This method involves the selective amplification
      of a DNA fragment from human beta globin gene with specific oligonucleotide
      primers, followed by digestion with restriction enzymes that recognize
      artificially created or naturally occurring restriction sites. To detect the 4
      nucleotide deletion of codon 41-42, we introduced a single mismatch nucleotide
      into the 3' end of the upstream primer to create an artificial Taq I restriction
      site. With a similar approach, an artificial Rsa I site was generated to detect
      the nucleotide 654 mutation (C-->T) of IVS-2, and Alu I restriction site was
      created to detect the codon 17 mutation (A-->T), and EcoRI restriction site was
      created for the -28 mutation (A-->G), a Rsa I restriction site was created for
      the nucleotide 5 mutation (G-->C) of IVS-1, and a Spe I restriction site was
      created to distinguish the codon 71 (+T) and codon 71/72 (+A) mutations from a
      normal sequence. The other eight rare mutations that occur in the genes of the
      Chinese people naturally create or abolish restriction sites. Using this kind of
      approach, we are able to provide a simple, rapid, accurate, and nonradioactive
      method to detect the genetic defects of beta-thalassemia in the Chinese
      population. It should be used not only for routine screening but also for
      prenatal diagnosis.

PMID- 1391962
TI  - A deletional frameshift mutation of the beta-spectrin gene associated with
      elliptocytosis in spectrin Tokyo (beta 220/216).
AB  - A novel spectrin variant carrying a truncated beta-chain and designated Spectrin
      Tokyo (beta 220/216) is presented. It was associated with elliptocytosis and
      moderate uncompensated hemolysis. The dimer self-association was reduced. An
      increase of the alpha I 74-Kd fragment was detected upon partial trypsin
      digestion. Analysis of cDNA and genomic DNA showed a 1-base deletion in codon
      2059 (GCC AGC-->GCA GCT; Ala-Ser-->Ala-Ala) that belongs to exon X of spectrin
      beta-gene. A missense sequence extended down to (new) codon 2075. Serine 2060, a
      potential phosphorylation site, was replaced by alanine. The shortened beta-chain
      failed to undergo phosphorylation in vitro. Spectrin Tokyo shared the same stop
      codon, overlapping normal codons 2076 and 2077 (CTG AAA), as Spectrin Nice (beta
      220/216), which is caused by a dinucleotide insertion in codon 2046 and contains
      2076 amino acids. However, for some reason, Spectrin Tokyo had a lower
      incorporation level into the membrane than Spectrin Nice.

PMID- 1391963
TI  - Fetal compensation of the hemolytic anemia in mice homozygous for the
      normoblastosis (nb) mutation.
AB  - The mouse autosomal recessive mutation nb causes a deficiency of erythroid
      ankyrin and generates a life-threatening hemolytic anemia in adult mice; however,
      at birth, nb/nb mice appear to be robust and show no pallor. In our study, the
      time of disease onset was sought by comparison of nb/nb and +/? mice both in
      utero and postnatally. Erythroid ankyrin messenger RNA (mRNA) is expressed in
      fetal erythroid progenitors from normal mice, but is reduced to 10% of normal
      levels in mutant fetuses. Despite the deficiency of erythroid ankyrin mRNA, 16
      and 18 day nb/nb fetuses have normal levels of red blood cells (RBCs) and the
      RBCs are morphologically normal by scanning electron microscopy. The earliest
      signs of any clinical anomaly are an increase in the number of circulating
      reticulocytes and the deposition of minor amounts of iron just before birth in
      the 18 day fetal nb/nb liver, suggesting that RBCs are being destroyed. Within 24
      hours after birth, nb/nb neonates have a slight but significant decrease of their
      RBC counts. During the next 5 days, the nb/nb RBC counts decrease markedly, the
      reticulocyte counts assume the mutant adult levels of 60%, the erythrocytes
      become microcytic and fragmented, and iron deposits accumulate in the liver. The
      rapid onset of clinical disease postnatally, coupled with our findings that the
      erythroid ankyrin gene is transcribed in fetal erythroid cell precursors from
      normal mice, suggest that mechanisms exist in the nb/nb fetus to compensate for
      the erythroid ankyrin deficiency.

PMID- 1391964
TI  - Allogeneic leukocytes but not therapeutic blood elements induce reactivation and
      dissemination of latent human immunodeficiency virus type 1 infection:
      implications for transfusion support of infected patients.
AB  - Various immunologic stimuli and heterologous viral regulatory elements have been
      shown to increase susceptibility to, and replication of, human immunodeficiency
      virus type 1 (HIV-1) in lymphocytes and monocytes in vitro. Transfusion of
      allogeneic blood components from heterologous donors constitutes a profound
      immunologic stimulus to the recipient, in addition to being a potential route of
      transmission of lymphotropic viral infections. To investigate the hypothesis that
      transfusions, and particularly those containing leukocytes, activate HIV-1
      replication in infected recipient cells, we cocultured peripheral blood
      mononuclear cells (PBMC) from three anti-HIV-1-positive individuals with
      allogeneic donor PBMC, as well as partially purified populations of donor
      lymphocytes, monocytes, granulocytes, platelets, and red blood cells (RBC) and
      allogeneic cell-free plasma. Allogeneic PBMC induced a dose-related activation of
      HIV-1 expression in in vivo infected cells, followed by dissemination of HIV-1 to
      previously uninfected patient cells. Activation of HIV-1 replication was observed
      with donor lymphocytes, monocytes, and granulocytes, whereas no effect was seen
      with leukocyte-depleted RBC, platelets, or plasma (ie, therapeutic blood
      constituents). Allogeneic donor PBMC were also shown to upregulate HIV-1
      expression in a "latently" infected cell line, and to increase susceptibility of
      heterologous donor PBMC to acute HIV-1 infection. Studies should be performed to
      evaluate whether transfusions of leukocyte-containing blood components accelerate
      HIV-1 dissemination and disease progression in vivo. If so, HIV-1-infected
      patients should be transfused as infrequently as possible and leukocyte-depleted
      (filtered) blood components should be used to avoid this complication.

PMID- 1391965
TI  - Evidence that the antigens of the Yt blood group system are located on human
      erythrocyte acetylcholinesterase.
AB  - The Yt blood group system comprises two antigens, Yta and Ytb. Human anti-Yta and
      human anti-Ytb immune precipitate a component of the same apparent molecular
      weight as acetylcholinesterase from radioiodinated erythrocytes of appropriate Yt
      phenotype. Immune precipitates obtained with anti-Yta and anti-Ytb contained
      acetylcholinesterase activity. In contrast, immune precipitates obtained with
      human anti-Gya and murine monoclonal anti-CD55, which identify other
      glycosylphosphatidylinositol-linked erythrocyte surface proteins, did not have
      acetylcholinesterase activity. Quantitative binding assays using murine
      monoclonal antiacetylcholinesterase antibodies (AE-1 and AE-2) gave 3,000 to
      5,000 binding sites/cell for IgG and 7,000 to 10,000 sites/cell for Fab
      fragments. Endo F digestion of immune precipitates obtained with AE-1 and anti
      Yta indicated that approximately 10% of the enzyme comprises N-glycans. These
      results indicate that the Yt antigens define an inherited polymorphism on
      erythrocyte acetylcholinesterase and that the recent assignment of the Yt blood
      group locus to the long arm of chromosome 7 (Zelinski et al, Genomics 11:165,
      1991) provisionally identifies the position of the acetylcholinesterase gene.

PMID- 1391966
TI  - Prevention of veno-occlusive disease of the liver after bone marrow
      transplantation: heparin or no heparin?

PMID- 1391967
TI  - Point mutations of rhodopsin gene found in Japanese families with autosomal
      dominant retinitis pigmentosa (ADRP).
AB  - The mutations of codon 17, 23, 58, and 347 of rhodopsin gene were investigated in
      24 unrelated Japanese families including 33 patients with autosomal dominant
      retinitis pigmentosa (ADRP). A patient with codon 17 mutation (Thr-17-Met, ACG-
      >ATG) and a family including 4 patients with codon 347 mutation (Pro-347-Leu, CCG
      ->CTG) were detected among them. Their clinical findings were extremely different
      between the two mutations. The former showed type 2 and the latter showed type 1
      ADRP. No mutation of codon 23 and 58 was detected in any families so far analyzed
      in the present study. Clinical findings associated with the mutation in codon 17
      and 347 of the rhodopsin gene show an existence of allelic heterogeneity.

PMID- 1391968
TI  - Assignment of the human cytochrome P-450 nifedipine oxidase gene (CYP3A4) to
      chromosome 7 at band q22.1 by fluorescence in situ hybridization.
AB  - We have used a full length cDNA clone (2.2 kb) for the human cytochrome P-450
      nifedipine oxidase (CYP3A4) enzyme as a probe to determine its chromosome
      localization by fluorescence in situ hybridization. CYP3A4 was mapped on R-banded
      human prometaphase chromosomes, and the precise localization of CYP3A4 on
      chromosome 7 was further confirmed by a delineation of G-banded pattern on the
      same prometaphase chromosomes through a combination of UV-filter. We assigned
      CYP3A4 to chromosome 7 at q22.1.

PMID- 1391969
TI  - Detection of variation in the ribosomal RNA gene clusters by a modified
      fluorescence in situ hybridization method.
AB  - Physical mapping of genes by fluorescence in situ hybridization (FISH) has become
      routine using fluorescein isothiocyanate (FITC) for probe detection and propidium
      iodide (PI) for chromosome staining. We have modified this conventional FISH
      method in a way that utilizes Texas red (TR) for signal detection and quinacrine
      mustard (QM) for chromosome banding. Using this Texas red and quinacrine (TRQ)
      method, we were able to identify individual acrocentric chromosomes with varying
      degrees of ribosomal RNA gene clusters. Two acrocentric chromosomes were found to
      carry extremely small number of rRNA gene copies as compared to the other eight
      counterparts in human diploid lymphoblastoid cell line GM00130B. Thus, the TRQ
      method allows one to probe for a specific sequence while identifying individual
      chromosomes and will be powerful for the chromosomal localization of various
      genes.

PMID- 1391970
TI  - Genetic polymorphism of human factor H (HF, beta 1H globulin) in Chinese Han
      population in northeast China.
AB  - The distribution of human factor H of serum phenotypes were studied using
      ultrathin polyacrylamide gel isoelectric focusing (PAGIEF) and subsequent
      immunoblotting techniques in 203 Chinese of Han population in Liaoning Province
      of northeast China. The gene frequencies of HF*A and HF*B were 0.4828 and 0.5172,
      respectively. All the observed numbers of the phenotypes were in agreement with
      the expected numbers under the Hardy-Weinberg equilibrium. The gene frequencies
      among Chinese, Japanese, and Caucasian populations were compared.

PMID- 1391972
TI  - Terminal deletion of the short arm of chromosome 3.
AB  - A boy with growth and mental retardation, flat occiput, high and broad forehead,
      blepharoptosis, narrow palpebral fissures, low set, malformed ears, short neck,
      anal atresia, deep sacral dimple is reported. High-resolution banding analysis
      showed terminal deletion of the short arm of chromosome 3 (46,XY,del(3)(p25.3)).
      Deletions of the short arm of chromosome 3 are relatively rare. The clinical
      features of the patient are compared with those of 19 previously reported cases.

PMID- 1391971
TI  - DNA analysis of two patients with a non-fluorescent Y chromosome.
AB  - Results of DNA study on two patients of gonadal dysgenesis with a 45,X/46,X,Ynf
      (non-fluorescent Y chromosome) karyotype are described. In one patient who
      developed gonadoblastoma, all 12 loci on the non-fluorescent part of Yq were
      detected. Another patient did not have gonadoblastoma at 20 years, and only the
      proximal 6 loci out of 12 were detected.

PMID- 1391974
TI  - A demonstration that breast cancer recurrence can be predicted by neural network
      analysis.
AB  - Neural Network Analysis, a form of artificial intelligence, was successfully used
      to predict the clinical outcome of node-positive breast cancer patients. A Neural
      Network was trained to predict clinical outcome using prognostic information from
      1008 patients. During training, the network received as input information tumor
      hormone receptor status, DNA index and S-phase determination by flow cytometry,
      tumor size, number of axillary lymph nodes involved with tumor, and age of the
      patient, as well as length of clinical followup, relapse status, and time of
      relapse. The ability of the trained Network to determine relapse probability was
      then validated in a separate set of 960 patients. The Neural Network was as
      powerful as Cox Regression Modeling in identifying breast cancer patients at high
      and low risk for relapse.

PMID- 1391973
TI  - Inhibition of growth of MCF-7 MIII human breast carcinoma in nude mice by
      treatment with agonists or antagonists of LH-RH.
AB  - Human breast carcinoma (MCF-7 MIII), which exhibits an estrogen-independent but
      estrogen-responsive phenotype, was xenografted in 8-9-week-old intact female
      athymic nude mice without estrogen supplementation. In this model, we
      investigated inhibitory effects of the modern luteinizing hormone-releasing
      hormone (LH-RH) antagonist SB-75 and the agonist D-Trp6-LH-RH. The analogs were
      administered in the form of sustained delivery systems (microcapsules and
      microgranules). In the first experiment, treatment lasted 10 weeks. After 9 weeks
      of treatment, a significant inhibition of tumor volume was first found only in
      the group treated with SB-75, but the final tumor volume was significantly
      suppressed both by D-Trp6-LH-RH and SB-75. In the second experiment, treatment
      was started 70 days after tumor transplantation and was continued for 6 weeks.
      Chronic treatment with SB-75 or D-Trp6-LH-RH appeared to completely arrest tumor
      growth as measured by tumor volume, percentage change in tumor volume, and tumor
      weight. Serum estradiol was suppressed to undetectable levels and LH levels were
      also diminished. Histologically, the regressive changes in the treated tumors
      were due to the enhancement of apoptosis (programmed cell death) of tumor cells.
      Membrane receptor assays showed that LH-RH binding sites were down-regulated in
      tumor cells after treatment with SB-75 or D-Trp6-LH-RH. The results indicate that
      the antagonist SB-75, released from sustained delivery systems, can inhibit the
      growth of MCF-7 MIII tumors as effectively as the agonist D-Trp6-LH-RH, but more
      rapidly. In view of its immediate blockade of the pituitary-gonadal axis and the
      absence of side effects, the LH-RH antagonist SB-75 might be considered as a
      possible new hormonal agent for the treatment of breast cancer.

PMID- 1391976
TI  - Genetic evolution of breast cancer: II. Relationship with estrogen and
      progesterone receptor expression.
AB  - The expression of estrogen (ER) and progesterone (PR) receptors was assayed by
      steroid binding in a series of 95 malignant breast tumors, for which the analysis
      of chromosome aberrations was performed and allowed the reconstruction of their
      chromosomal evolution. It was shown that breast tumors undergo a progressive loss
      of chromosomes, with occasionally one and rarely two endoreduplications.
      Chromosome losses were often the consequence of rearrangements, and the rate of
      rearranged chromosomes, which increases progressively, appeared as a possible
      indicator of tumor progression. The distribution of ER and PR values in the
      sample of 95 tumors was compared to that of a larger control series of
      consecutive cases: 598 for ER and 460 for PR. The similarities of the
      distributions indicated that the sample of 95 tumors was representative of the
      general population of breast cancers. The levels of ER and PR expression were
      very strongly and negatively correlated to the rate of rearranged chromosomes,
      but not to the modal number of chromosomes. However, when tumors having either
      undergone endoreduplication or not (greater than 50 or less than 51 chromosomes,
      respectively) were considered separately, a significant correlation between ER
      and PR expression and chromosome number was found within each group. Finally,
      breast cancers were subdivided into 4 stages of cytogenetic evolution, from the
      least to the most evolved: stage 1: less than or equal to 50 chromosomes, less
      than 25% rearranged chromosomes; stage 2: greater than 50 chromosomes, less than
      25% rearranged chromosomes; stage 3: less than or equal to 50 chromosomes,
      greater than 25% rearranged chromosomes; stage 4: greater than 50 chromosomes,
      greater than 25% rearranged chromosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1391975
TI  - Racial differences in cancer of the male breast--15 year experience in the
      Detroit metropolitan area.
AB  - Characteristics of cancer of the male breast were evaluated in a population based
      review of 244 cases identified retrospectively through the Metropolitan Detroit
      Cancer Surveillance System (MDCSS) between 1973 and 1987. The mean age at
      diagnosis was 65 years and median survival time, 44 months. There were no
      apparent time trends in incidence for either white or black men from 1973 through
      1987. Modified radical mastectomy was the most common surgical procedure, while
      simple and radical mastectomy declined in popularity over time. Cox's
      proportional hazards regression model was used to test the simultaneous effects
      of age, race, stage, and treatment on survival. Men older than 65 at diagnosis
      had a greater risk of dying than men under 65 (RR 1.52, 95% confidence interval,
      1.01-2.28). Survival was significantly worse for men who presented at a more
      advanced stage; regional versus localized (RR 2.19, 95% confidence interval, 1.39
      3.45) and remote versus localized (RR 4.31, 95% confidence interval 2.26-8.23).
      Race had no significant effect on survival in men with breast cancer in the
      Detroit Metropolitan Area.

PMID- 1391977
TI  - Weight gain after primary surgery for breast cancer--effect of tamoxifen.
AB  - Changes in body weight have been studied in 92 consecutive patients with primary
      breast cancer from the time of initial diagnosis and treatment. Sixty patients
      receiving tamoxifen were compared with 32 controls receiving no hormone
      treatment. Weight gain was seen in both groups, but was greater in the group
      receiving tamoxifen. Premenopausal women receiving tamoxifen had greater weight
      gain than postmenopausal women on tamoxifen therapy.

PMID- 1391978
TI  - 1 alpha-hydroxyvitamin D3, hypercalcemia, and growth suppression of 7,12
      dimethylbenz[a]anthracene-induced rat mammary tumors.
AB  - 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] was administered to female Sprague
      Dawley rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. 1
      alpha(OH)D3 suppressed the growth of the rat mammary tumors dose-dependently, and
      in the high dose groups treated with 0.5-1.0 micrograms/kg of 1 alpha(OH)D3,
      significant inhibition of tumor growth was observed. But daily oral
      administration of 1 alpha(OH)D3 for four consecutive weeks caused side effects
      such as hypercalcemia and weight loss. We compared 0.5 microgram/kg of 1
      alpha(OH)D3 three times weekly with the same dose six times weekly to discover
      whether or not the side effects can be reduced by treatment schedule. Both groups
      showed a significant oncostatic effect, compared with the control group, while
      the side effects were relieved in the three times weekly group. Regarding
      estrogen receptors (ER) in the tumors, there was no significant difference among
      the groups. These results suggested that the antitumor effect of 1 alpha(OH)D3 on
      DMBA-induced mammary tumors was not related to ER status. Combined use of 1
      alpha(OH)D3 with 5-fluorouracil (5-FU) or medroxyprogesterone acetate (MPA) was
      also examined. No significant augmentation of the antitumor effect was seen in
      the two combinations, although the combined therapy with MPA showed a significant
      inhibition of weight loss in the rats.

PMID- 1391979
TI  - Epidermal growth factor receptor in breast cancer: storage conditions affecting
      measurement, and relationship to steroid receptors.
AB  - This study investigates the effect of freezing and storage of tissue and
      subcellular fractions on the measurement of epidermal growth factor receptors
      (EGF-r); compares competition binding and single saturating dose assays (SSD) for
      quantitating EGF-r levels; investigates several tissues as potential quality
      control; and examines the relationship between EGF-r and hormone receptor
      expression in human breast cancers. Mouse and calf uterine cell membranes were
      preferred sources of quality control tissue with similar levels of high affinity
      EGF-r to human breast cancer tissue (less than 150-200 fmol/mg membrane protein).
      Studies using pooled mouse uterine tissues indicated a loss of 40% in EGF-r
      activity following a single-20 degrees C freeze/thaw cycle, while a breast cancer
      tissue showed a 75% loss, independent of storage temperature (liquid nitrogen, 
      70 degrees C, -20 degrees C). A single freeze/thaw cycle of mouse uterine broken
      cell pellets (nuclei plus membrane fraction) again indicated a loss of EGF-r
      irrespective of storage temperature (43% loss at -70 degrees C, 52% loss at -20
      degrees C). In most cases irrespective of the tissue type or tissue fraction
      being stored, the length of storage had little impact on the extent of the loss
      in activity. A second freeze/thaw cycle of intact tissue, or freezing of broken
      cell pellets from a previously-frozen tissue, led to a further major or total
      loss of the remaining EGF-r. Overall these results are commensurate with the
      published effects of freezing and storage on estrogen receptor measurement. In
      addition, our studies suggest that the most suitable procedure for assaying
      frozen breast cancer specimens for EGF-r levels in conjunction with steroid
      receptor quantitation is to prepare and assay both cytosol and membrane fractions
      for their respective receptor content without further storage. A concordance of
      86% was found in 44 breast cancers assayed for EGF-4 by saturation analysis and
      SSD. Statistically significant inverse relationships were found between EGF-r and
      estrogen and progesterone receptor levels in the study of approximately 350
      breast cancer patients. No association was found with tumor stage or diameter,
      axillary node involvement, or patient age.

PMID- 1391980
TI  - Tamoxifen metabolism is altered by simultaneous administration of
      medroxyprogesterone acetate in breast cancer patients.
AB  - We have measured the levels of tamoxifen and three of its metabolites in the
      blood of patients receiving tamoxifen alone or combination therapy with tamoxifen
      and medroxyprogesterone acetate. Our results indicate that addition of the
      progestogen significantly alters the metabolism of tamoxifen over a six-month
      period. We suggest that the interaction between these drugs may involve
      additional sites (probably hepatic) besides the desired target tumour.

PMID- 1391981
TI  - Regulation of estrogen sulfotransferase by estrogen in MCF-7 human mammary cancer
      cells.
AB  - The importance of the steroid hormone microenvironment within cells is now
      recognised in studies on endocrine-related neoplasms such as breast cancer. This
      focuses attention on enzymes which control the intracellular levels of estradiol
      17 beta (E2). One such enzyme, estrogen sulfotransferase, which converts E2 to
      inactive E2-3 sulfate, has now been shown to be regulated by estrogen in MCF-7
      human mammary cancer cells. Hydroxysteroid sulfotransferase, which sulfurylates
      the adrenal-derived estrogen 5-androstene-3 beta,17 beta-diol, is also under
      estrogen control. Evidence is provided which shows that one function of these
      enzymes may involve elimination of estrogen from the cell following processing of
      the ligand-charged estrogen receptor (ER).

PMID- 1391982
TI  - U.K. National Breast Screening Programme: first year experience at a
      histopathology department in an assessment/treating centre.

PMID- 1391983
TI  - Comment on 'Breast deformity, its correction, and assessment of breast conserving
      surgery'.

PMID- 1391984
TI  - Integrating prognostic factors.
AB  - This special issue of Breast Cancer Research and Treatment addresses the topic of
      how to evaluate new prognostic factors for breast cancer, and how the information
      provided by these new factors might be integrated with traditional factors to
      make better treatment decisions for these patients. Although the focus is on
      breast cancer, the techniques described are equally applicable to any situation
      involving survival or failure over time.

PMID- 1391985
TI  - Prognostic factors in clinical trials.
AB  - Prognostic factors define the study population, help formulate the study
      objectives, and influence the treatment strategies. They must be accounted for in
      the study analysis to obtain valid estimates of the treatment differences and to
      evaluate results across studies. The causal relationship between a prognostic
      factor and the study endpoint can only be established through prospective
      randomized study designs. Potential factors discovered through retrospective
      analysis must be verified to establish their validity. Using such factors
      prematurely to select patient population and treatment strategy for a new study
      will not establish the validity of the potentially important factor.

PMID- 1391986
TI  - Why do so many prognostic factors fail to pan out?
AB  - Although there can be many reasons that one study fails to confirm the results of
      another, the consequences of data exploration and the potential for spuriously
      significant results are often overlooked. A series of simulation experiments were
      designed to mimic the characteristics of relapse-free survival data that might be
      encountered in a prognostic factor study of node-negative breast cancer patients.
      Each simulated dataset of 500 or 250 cases was divided into a training set, used
      to select the "best" prognostic factor cutpoint, and a validation set, used to
      confirm the cutpoint. Testing multiple cutpoints markedly increased the risk of
      making a Type I error. The power to detect even small true differences was
      substantial, and increased as the number of cutpoints increased. Regardless of
      the number of cutpoints tested on the training sets, the Type I error rate on an
      independent validation data set was quite stable and the power of the validation
      set to detect true differences was not related to the number of cutpoints.
      Validation power closely approximated that predicted for a simple two group
      comparison. It is therefore recommended that exploratory analyses of prognostic
      factors formally employ some method of adjusting for increased Type I errors,
      such as independent validation sets, ad hoc adjustment factors, or other
      statistical methods of estimating the true risk.

PMID- 1391989
TI  - A graphical approach to the analysis of censored data.
AB  - The presence of censoring has hampered the graphical exploration of survival
      data. We present several graphical approaches to the analysis of such data here,
      many based on functionals of the distribution function and estimated using the
      Kaplan-Meier estimate of the distribution function. Topics covered include
      comparing two samples, comparing many samples, and regression.

PMID- 1391988
TI  - Confirmation of a prognostic index for patients with metastatic breast cancer
      treated by endocrine therapy.
AB  - We have previously reported a retrospectively constructed index which can
      accurately predict survival at the time of diagnosis of symptomatic metastatic
      breast cancer. The index, derived from a Cox model, is scored: Index score = (4 x
      Grade)-(6 x ER) + (4 x SIMD)-(0.1 x DFI), where histological grade is scored 1-3
      (good, moderate, or poor), oestrogen receptor (ER) is scored 0 (negative) or 1
      (positive), site of initial metastasis (SIMD) is scored 1-4 for bone only, lung
      only, bone and lung, or visceral metastases, respectively, and disease-free
      interval (DFI) is measured in months. Patients were divided into three prognostic
      groups on the basis of index score. In the present study we have tested this
      index prospectively on a new group of 147 patients with metastatic breast cancer.
      The percentage of patients in each of the three groups was similar between the
      retrospective and prospective studies. In the prospective study the difference in
      survival between the 3 groups was highly significant (p less than 0.001),
      confirming our retrospective analysis. No single one of the four factors was as
      powerful in predicting survival as the index itself. We now use this index in our
      patient management.

PMID- 1391987
TI  - The Nottingham Prognostic Index in primary breast cancer.
AB  - In 1982 we constructed a prognostic index for patients with primary, operable
      breast cancer. This index was based on a retrospective analysis of 9 factors in
      387 patients. Only 3 of the factors (tumour size, stage of disease, and tumour
      grade) remained significant on multivariate analysis. The index was subsequently
      validated in a prospective study of 320 patients. We now present the results of
      applying this prognostic index to all of the first 1,629 patients in our series
      of operable breast cancer up to the age of 70. We have used the index to define
      three subsets of patients with different chances of dying from breast cancer: 1)
      good prognosis, comprising 29% of patients with 80% 15-year survival; 2) moderate
      prognosis, 54% of patients with 42% 15-year survival; 3) poor prognosis, 17% of
      patients with 13% 15-year survival. The 15-year survival of an age-matched female
      population was 83%.

PMID- 1391990
TI  - Flexible covariate effects in the proportional hazards model.
AB  - The proportional hazards model is frequently used in analyzing the results of
      clinical trials, when it is often the case that the outcomes are right-censored.
      This model allows one to measure treatment effects and simultaneously identify
      and adjust for prognostic factors that might influence the outcome. In this
      paper, we outline a class of semiparametric models that allows one to model
      prognostic factors nonlinearly, and have the data suggest the form of their
      effect. The methods are illustrated in an analysis of data from a breast cancer
      clinical trial.

PMID- 1391991
TI  - Making the most of your prognostic factors: presenting a more accurate survival
      model for breast cancer patients.
AB  - Determining an appropriate level of adjuvant therapy is one of the most difficult
      facets of treating breast cancer patients. Although the myriad of prognostic
      factors aid in this decision, often they give conflicting reports of a patient's
      prognosis. What we need is a survival model which can properly utilize the
      information contained in these factors and give an accurate, reliable account of
      the patient's probability of recurrence. We also need a method of evaluating
      these models' predictive ability instead of simply measuring goodness-of-fit, as
      is currently done. Often, prognostic factors are broken into two categories such
      as positive or negative. But this dichotomization may hide valuable prognostic
      information. We investigated whether continuous representations of factors,
      including standard transformations--logarithmic, square root, categorical, and
      smoothers--might more accurately estimate the underlying relationship between
      each factor and survival. We chose the logistic regression model, a special case
      of the commonly used Cox model, to test our hypothesis. The model containing
      continuous transformed factors fit the data more closely than the model
      containing the traditional dichotomized factors. In order to appropriately
      evaluate these models, we introduce three predictive validity statistics--the
      Calibration score, the Overall Calibration score, and the Brier score--designed
      to assess the model's accuracy and reliability. These standardized scores showed
      the transformed factors predicted three year survival accurately and reliably.
      The scores can also be used to assess models or compare across studies.

PMID- 1391992
TI  - A comparison of all-subset Cox and accelerated failure time models with Cox step
      wise regression for node-positive breast cancer.
AB  - Clinical studies usually employ Cox step-wise regression for multivariate
      investigations of prognostic factors. However, commercial packages now allow the
      consideration of accelerated failure time models (exponential, Weibull, log
      logistic, and log normal), if the underlying Cox assumption of proportional
      hazards is inappropriate. All-subset regressions are feasible for all these
      models. We studied a group of 378 node positive primary breast cancer patients
      accrued at the Henrietta Banting Breast Centre of Women's College Hospital,
      University of Toronto, between January 1, 1977, and December 31, 1986. 85% of
      these patients had complete prognostic factor data for multivariate analysis, and
      96% of the patients were followed to 1990. There was evidence of marked
      departures from the proportional hazards assumption with two prognostic factors,
      number of positive nodes and adjuvant systemic therapy. The data strongly
      supported the log normal model. The all-subset regressions indicated that three
      models were similarly good. The variables 1) number of positive nodes, 2) tumour
      size, and 3) adjuvant systemic therapy were included in all three models along
      with one of three biochemical receptor variables 1) ER, 2) combined receptor (ER-
      PgR-; ER+PgR-; ER- PgR+; ER+PgR+; or 3) PgR. Better multivariate modeling was
      achieved by using quantitative prognostic factors, a check for appropriate
      underlying model-type, and all-subset variable selection. All-subset regressions
      should be considered for routine use with the many new prognostic factors
      currently under evaluation; it is very possible that there may not be a single
      model that is substantially better than others with the same number of variables.

PMID- 1391994
TI  - A practical application of neural network analysis for predicting outcome of
      individual breast cancer patients.
AB  - It has been previously shown that Neural Networks can be trained to recognize
      individual breast cancer patients at high and low risk for recurrent disease and
      death. This paper expands on the initial investigation and shows that by coding
      time as one of the prognostic variables, a Neural Network can use censored
      survival data to predict patient outcome over time. In this demonstration a
      Neural Network was trained, tested, and validated using censored survival data
      from a group of 1373 patients with node-positive breast cancer. The Neural
      Network method predicted patient outcome as accurately as Cox Regression
      modeling. The final Neural Network model can be presented with a patient's
      prognostic information and make a series of predictions about probability of
      relapse at different times of follow-up, allowing one to draw survival
      probability curves for individual patients.

PMID- 1391993
TI  - Proportional hazards and recursive partitioning and amalgamation analyses of the
      Southwest Oncology Group node-positive adjuvant CMFVP breast cancer data base: a
      pilot study.
AB  - Several putative prognostic factors have been identified in node-positive breast
      cancer patients, but their importance needs to be clarified in a uniformly
      treated population. The objectives of this investigation were: 1) to describe the
      characteristics of a uniformly treated node-positive data base; 2) to use
      proportional hazards (Cox) and recursive partitioning and amalgamation (RPA)
      multivariate models to assess the importance of potential prognostic factors for
      disease-free and for overall survival; and 3) to define prognostic groups with
      different disease-free survival and survival outcomes with RPA. A data base of
      768 node-positive patients enrolled on 1-year adjuvant CMFVP arms of four SWOG
      trials was formed. Variables were number of positive nodes, age, age at
      menopause, menopausal status, ER status, ER and PgR levels (for RPA only), tumor
      size, race, breast cancer in mother, and obesity index. Independent predictors of
      both disease-free and overall survival in the Cox models were: number of positive
      nodes (4-6 worse than 1-3, and better than greater than 6); the age/menopause
      category (age greater than or equal to 35/premenopausal better than age less than
      35/premenopausal and better than postmenopausal); and ER status (patients on ER
      negative study worse than others). The RPA for disease-free survival defined four
      subgroups based on nodes, menopausal status, tumor size, and age at menopause (5
      year recurrence-free rates = 73%, 52%, 38%, and 15%). The RPA for survival found
      four prognostic groups, defined only by the number of positive nodes and ER and
      PgR levels (5-year survivals = 91%, 72%, 56%, and 37%). Both RPAs suggested
      interesting refinements of the results of the Cox models. In the RPA for disease
      free survival, best node cutoffs differed by menopausal status, tumor size was
      important only in postmenopausal patients with few positive nodes, and age at
      menopause emerged as an independent predictor of recurrence potential. And, the
      RPA for survival showed that node cutoffs differed according to ER level. Thus,
      these analyses underscore the value of simple, clinically available prognostic
      factors and suggest the possible need to reconsider the definition of good and
      poor risk patient groups in future adjuvant trial design.

PMID- 1391995
TI  - Dentistry and national health insurance.
AB  - Access to dental care is not equitable in the United States. The dental health of
      the population varies widely by socioeconomic status. Private dental insurance
      coverage has peaked at about 40% of the population, and benefits are variable.
      Dentistry is not included in Medicare and is optional for adults under Medicaid.
      Inflation is greater than for all goods and services. There is considerable
      administrative waste, and quality is variable. In this author's opinion, only a
      national system with universal coverage, one set of benefits, a single payer, a
      cap on expenditures, and no participation by insurance companies that is
      increasingly based on salaried consumer-or community-owned group practices with
      dentist input into decision making can hope to solve the existing problems.

PMID- 1391996
TI  - Bibliography of the current world literature. Oral and maxillofacial surgery.

PMID- 1391997
TI  - Bibliography of the current world literature. Infections.

PMID- 1391998
TI  - Temporomandibular joint surgery.
AB  - Rapid progress has been made in the field of temporomandibular joint (TMJ)
      surgery during the past decade. These developments are predominantly due to the
      ongoing refinement of imaging and operative techniques. Parallel to these
      changes, the new techniques of arthroscopic surgery have been introduced into
      standard therapy for internal derangement and osteoarthrosis, to some extent.
      Several earlier studies have shown that open and arthroscopic surgery have
      similar success rates. Therefore, the surgeon has to decide which method would
      combine the smallest risk of postoperative morbidity with the least operative
      effort. In this regard, arthrocentesis is inaugurated as a new operative method
      for treatment of the closed lock. However, the basic concepts of arthroscopic
      surgery seem to be contradictory to the concepts of open surgery, which have also
      been proven successfully. Thus, the success of arthroscopic methods challenges
      our understanding of the pathogenesis and pathophysiology of internal
      derangements and osteoarthrosis of the TMJ. Today, morphologic findings from
      either arthroscopy, magnetic resonance imaging and new findings in the field of
      joint physiology lead to plausible explanations for the etiology and
      symptomatology of internal derangements. This is discussed in several papers.
      Additionally, arthroscopy may very well be an appropriate method of investigating
      intra-articular changes in the TMJ caused by trauma. So far, our knowledge about
      these effects still seems to be insufficient. For several years, the literature
      has reflected an increasing discussion about alloplastic materials used for
      interpositioning in the TMJ. A more rational approach in estimating the potential
      risks of these materials seems to be highly necessary.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1392000
TI  - Advances in orthognathic surgery.
AB  - The basic treatment objectives in the management of patients with dentofacial
      deformities have remained unchanged. However, there have been significant
      advances in the evaluation and treatment planning of these patients. These
      advances can be divided into two major categories: the incorporation of
      concomitant or delayed adjunctive aesthetic procedures; and the treatment of
      select patients in an ambulatory setting. These advances have objectively
      improved postoperative results and patient comfort and have reduced the costs of
      traditional inpatient surgery. This article reviews the recent literature
      relative to both of these categories.

PMID- 1391999
TI  - Mandibular reconstruction with free bone grafts.
AB  - The ideal method for replacing lost mandibular bone would be to induce growth of
      host replacement bone that could bridge a defect by means of bone induction. In
      the coming years, both bone morphogenetic protein and guided tissue regeneration
      will certainly gain a lot of interest. For the time being, the best method of
      grafting is still autogenous bone, provided there is a suitable donor site,
      sufficient bone, and a vascularized graft bed. This review outlines different
      sources and methods for bone grafting. The possibility of using different
      substitutes for bone is also discussed, as a number of articles have recently
      dealt with this problem.

PMID- 1392001
TI  - New developments and advances in dental implantology.
AB  - Progress in laboratory investigation of the biologic basis of osseointegration
      coupled with an extensive world-wide clinical experience have created a better
      understanding of implant and tissue integration and has allowed expanded clinical
      applications. Techniques are now available to provide alloplastic tooth
      replacements that are biomechanically stable and predictable and provide adequate
      masticatory, phonetic, and esthetic function approximating that of the normal
      dentition. Computed tomography is now used to assist the surgeon in determining
      available recipient bone sites and to determine the exact three-dimensional
      positioning of endosseous implants in the jaw bone. Surgical management of bone
      volume deficiencies, utilizing grafting techniques with bone and bone substitutes
      and guided tissue regeneration with membrane barriers, have given previously
      rejected patients an opportunity to benefit from osseointegrated implants.
      Congenital and acquired bone defects may now be managed and reconstructed with
      techniques that include dental implant surgery. Osteoinductive and
      osteoconductive substances are now available to assist in accelerating healing
      and present great promise for future applications.

PMID- 1392002
TI  - Comparative imaging of the jaws.
AB  - Explosive growth in high-technology imaging continues in dentistry as in all
      health sciences. Some new technology will find its way into general and some
      specialty dental practices; two examples, digital intraoral radiography and
      multimodality panoramic machines, are reviewed. New developments in the
      application of current imaging procedures (both conventional and "high tech") to
      diagnosis and management of diseases and injuries of the jaws, muscles of
      mastication, and salivary glands are presented. Recent information suggests that
      the risk of radiation-induced cancer in exposed populations may be greater than
      had been recognized. The impact of this data on both occupational and patient
      radiation exposure in dentistry is reviewed.

PMID- 1392003
TI  - Bacteriology of periodontal disease.
AB  - The microbial flora associated with the periodontal tissues in health and disease
      is extremely complex, and much research is being directed toward identifying
      those species that may be etiologic agents or that can be used as prognostic
      indicators. Recent work has resulted in changes in the taxonomic position of
      several periodontal species and the recognition that several others, particularly
      species of Eubacterium and Peptostreptococcus, as well as a novel oral
      spirochete, may be important in disease. New rapid techniques for identifying and
      enumerating the periodontal flora are being applied to cross-sectional and
      longitudinal studies to assess the significance of the various species; the DNA
      probe and immunologic detection methods demonstrate both advantages and
      limitations when compared with methods based on determining the predominant
      cultivable flora.

PMID- 1392004
TI  - Immunization against dental caries.
AB  - The development of a vaccine against dental caries involves identification of
      appropriate antigens of mutans streptococci against which protective immune
      responses can be mounted, and the selection of a method of immunization that will
      generate sustained levels of salivary antibodies. Antigens receiving most
      attention include streptococcal surface proteins that are involved in attachment
      to tooth surfaces and glucosyltransferases that synthesize adhesive glucans from
      sucrose. Recent advances in mucosal immunology and the introduction of novel
      strategies for inducing mucosal immune responses now raise the possibility of
      constructing an effective and safe vaccine. Passive immunization by the oral
      application of performed antibodies against selected antigens of mutans
      streptococci has also shown promise and may facilitate understanding of the
      mechanisms of protective immunity against caries.

PMID- 1392005
TI  - The role of oral microorganisms in cancer therapy.
AB  - It has been assumed that the principal changes that occur in the oral flora
      during cancer therapy are yeast and gram-positive coccal proliferation. Recent
      studies have shown that treatment with topical antifungals or disinfectants has
      failed to relieve such complications as irradiation mucositis that occur during
      anticancer therapy. Thus, many of the oral lesions observed during treatment are
      not due to candidiasis or streptococcal infection. It has been shown that
      anticancer therapy impairs or reduces the carriage defense of the oropharynx and
      is accompanied by colonization and proliferation of gram-negative bacilli. It is
      argued that if oral infectious complications are to be prevented during
      anticancer therapy, then the selective elimination of gram-negative bacilli may
      be indicated.

PMID- 1392006
TI  - Antimicrobial prophylaxis in oral surgery.
AB  - Administration of antimicrobial prophylaxis is advocated in procedures with a
      high risk of surgical wound infection. Recent advances in knowledge in this area
      include the broader recognition of risk factors that better predict the expected
      incidence of postoperative surgical wound infection than does the traditional
      wound classification system. In oral surgery, guidelines for antimicrobial
      prophylaxis based on established principles exist in the literature, and
      antimicrobial prophylaxis has been demonstrated to be effective in preventing
      postoperative surgical wound infection. However, surveys suggest that fundamental
      principles are often ignored, and antibiotics are often initiated at an
      inappropriate time and are continued beyond the time required to be influential
      on reduction of infection rates.

PMID- 1392008
TI  - Health care, politics and the upcoming election.

PMID- 1392007
TI  - Third molar surgery.
AB  - There have been significant advances in the diagnosis and treatment of impacted
      third molars with special emphasis on periodontal health in the second molar area
      adjacent to the extraction site. A thorough discussion addresses these advances
      and their impact on treatment planning of asymptomatic impacted third molars.

PMID- 1392009
TI  - Meeting the challenge of mentoring African American nursing faculty: a strategy
      for professional development.
AB  - Is mentoring just another bandwagon for African American and minorities to jump
      on? My personal perspective is that we should examine in more detail and dialogue
      the notions of self-actualization and affirmation that several authors identified
      as the essence of mentoring minorities. Then, particular distinctions among
      concepts such as mentor, master role model, preceptor, "buddy," or whatever might
      be seen as variations on the main theme of personal and professional self
      actualization. Given what it may accomplish, appropriate mentoring for the
      African American nursing faculty neophyte is a challenge for the nursing
      profession and a strategy for institutional advancement in the twenty first
      century.

PMID- 1392010
TI  - Mentoring role of black nursing faculty members.

PMID- 1392011
TI  - Adenosine deaminase activity in the human duodenal mucosa in relation to gastric
      acid secretion.
AB  - Adenosine deaminase (ADA) activity was estimated in mucosal specimens obtained
      endoscopically from the duodenal bulb. Three groups of subjects were studied: 1.
      9 patients with achlorhydria, 2. 12 subjects with normal gastric acid secretion,
      3. 5 patients with hypersecretion. Enzyme activity was measured by determination
      of ammonia liberated from the substrate according to the Chaney and Marbach
      method. In patients with hypersecretion the ADA activity was lower than in those
      with achlorhydria (p less than 0.001) and normal acid secretion (p less than
      0.02). A significant negative correlation between ADA activity in the duodenal
      bulb mucosa and basal and maximal gastric acid outputs was found. The present
      study seems to indicate a possible relationship between gastric acid secretion
      and duodenal ADA activity.

PMID- 1392012
TI  - The vasopressin and oxytocin neurohypophysial content as influenced by bleeding
      or dehydration: effect of cholecystokinin octapeptide.
AB  - The effect of CCK-8 (50 ng, i.c.v.) on the neurohypophysial vasopressin and
      oxytocin storage was estimated in haemorrhaged (1 ml per 100 g b.w.) male Wistar
      rats. In another experimental series rats dehydrated for three days were given
      CCK-8 in a daily i.c.v. dose of 50 ng. The neurohypophysial vasopressin and
      oxytocin content was bioassayed by pressor effect following Dekanski or milk
      ejection activity in vitro following van Dongen and Hays, respectively. The
      decrease of neurohypophysial vasopressin and oxytocin content, brought about by
      dehydration, was significantly less marked in animals treated with CCK-8. The
      depletion of neurohypophysial vasopressin and oxytocin content in haemorrhaged
      animals could be completely inhibited by earlier i.c.v. administration of CCK-8.
      It is suggested that hypothalamic cholecystokinin may serve as a modulator of
      neurohypophysial function.

PMID- 1392013
TI  - A moderate dose of cycloheximide does not prevent the febrile response to
      endotoxin but interfere with induction of pyrogenic tolerance in rabbit.
AB  - The purpose of the present study was to examine the effect of cycloheximide (Cx)-
      inhibitor of protein synthesis, on the development of pyrogenic tolerance to LPS.
      It has been observed that Cx at a dose of 1 mg/kg given intravenously 1 h prior
      to LPS did not prevent fever response, however it modified the induction of
      pyrogenic tolerance. It was manifested in existence of the second phase of fever
      after the following administrations of LPS into rabbits pretreated with Cx. In
      control group of rabbits the induction of pyrogenic tolerance was accompanied
      with decaying of the second peak of fever visible as early as the second dose of
      LPS.

PMID- 1392014
TI  - Angiotensin II--derived peptides devoid of phenylalanine in position 8 have full
      psychotropic activity of the parent hormone.
AB  - In this work we compared in rats the influence of heptapeptide 1-7-angiotensin
      II, hexapeptide 2-7-angiotensin II, pentapeptide 3-7-angiotensin II and
      angiotensin II on motility, stereotypy, learning of conditioned avoidance
      responses and recall of passive avoidance behaviour allowing to avoid aversive
      stimulation. The 4 peptides administered 15 min before the experiment, tended to
      increase the number of crossings, rearings and bar approaches in open field,
      significantly accelerated acquisition of conditioned avoidance responses and
      improved recall of the passive avoidance. All the peptides applied immediately
      before the experiment intensified stereotypy evoked by apomorphine in the dose 1
      mg/kg and amphetamine in the dose 6.5 mg/kg given intraperitoneally. These
      results show full psychotropic activity of the examined fragments of angiotensin
      II, comparable with the activity of the parent octapeptide. Our previous
      hypothesis that the Val-Tyr-Ile-His-Pro fragment of angiotensin II is responsible
      for the psychotropic activity evoked by angiotensins in rats is thus confirmed.

PMID- 1392015
TI  - Evidence for an infarctive pathogenesis of acute and chronic gastroduodenal
      ulceration.
AB  - It is clear that all mucosal defensive mechanisms acting against aggressive
      ulcerogenic factors depend on adequate blood flow. When defence is active, ulcers
      tend to heal and do so faster when luminal aggression is prevented by reduction
      of acidity or eradication of H. pylori. Such successful treatment is so
      profitable that pharmaceutical companies invest vast fortunes on research into
      every aspect of therapy. This may explain why research on basic aetiology has
      been slower. Nevertheless there have been recent advances which increasingly
      point towards an ischaemic pathogenesis of both acute and chronic ulcers. We have
      been studying those ischaemic mechanisms that may be triggered by alteration of
      normal physiological processes, and we now have a body of evidence supporting an
      infarction-like mechanism induced by abnormal motility which might explain the
      initiation of both acute and chronic human ulceration. In this article we review
      the evidence for this and show that such a pathogenesis is compatible with the
      features and current concepts of gastro-duodenal ulceration. Perhaps the most
      striking feature of chronic ulcers is their singularity, and localisation to the
      lesser curvature and first part of the duodenum. Within the lesser curvature
      there is an increasing incidence from the oesophageal end towards pylorus, with
      maximal incidence in the incisural area (1). Duodenal ulcers occur on the
      anterior or posterior walls of the first 4 cm. uncommonly on the superior "cap"
      and rarely on the inferior wall. Such localisation points to a primary cause
      which, by analogy with other localised necroses eg coronary or stroke, is usually
      an infarction of an end-artery system.

PMID- 1392016
TI  - Hyperuricemia induced by fructose load in liver cirrhosis.
AB  - The intravenous administration of fructose in healthy subjects may induce an
      increase of blood uric acid and the urinary excretion of urate and xanthine as a
      result of hepatic adenosine triphosphate (ATP) breakdown. These changes are
      partially reversed by ATP resynthesis. We studied the effect of fructose load
      (0.5 g/kg body weight) on the products of ATP metabolism, and the interference of
      fructose on the galactose test in 10 patients with well compensated cirrhosis
      compared with 10 healthy controls. The fructose and the fructose/galactose loads
      induced a significantly greater increase of plasma uric acid in cirrhotics than
      in controls, with a 60 minute peak in the cirrhotics. Urinary excretion of urate
      and xanthines was significantly increased (p less than 0.001) only in the
      cirrhotics after the fructose/galactose load. As expected, the galactose
      elimination capacity (GEC) calculated with the galactose test, was lower in these
      patients than in controls. Fructose infusion before galactose did not
      significantly modify the GEC in either of the two groups compared. The higher
      uric acid increase induced by fructose in the blood of cirrhotic patients seems
      to be a good marker of the energy crisis of the diseased liver whereby it is
      unable to efficiently resynthesize ATP from its breakdown products.

PMID- 1392017
TI  - Preliminary observations in the fasting serum gastrin in patients with duodenal
      ulcer; further evidence of the "clearing" effect of omeprazole on H pylori?
AB  - Thirty patients with active duodenal ulcer who were Helicobacter pylori positive
      (HP+) by HLO test and by histology (Giemsa stain) were given omeprazole (OME) 20
      mg/d for a two-week period. Estimation of fasting serum gastrin concentration
      (RIA) was performed before treatment and 24 hours after the last dosage of OME,
      and HP was searched for an antral biopsies at the end of the treatment as well.
      Mean fasting serum gastrin concentration increased significantly after treatment
      in all patients studied (p less than 0.05). However, the increase remained
      significant only in those patients who continued to be HP+ while no significant
      increase was observed in those who became HP-. The results could be considered as
      further evidence of the 'clearing' effect of Omeprazole on HP.

PMID- 1392018
TI  - Sucralphate in the prevention of acute gastric lesions induced by ischemia
      reperfusion.
AB  - The role of sucralphate in prevention of acute gastric injuries and its
      comparison with free radical blockers such as allopurinol, soybean trypsin
      inhibitor and superoxidase dismutase in the ischemia-reperfusion model by total
      occlusion of the coeliac artery in Wistar rats, was studied. The gross gastric
      mucosal necrotic area was 80%. In contrast with the antioxidant drugs the
      necrotic area attained was between 7 to 15%, while with sucralphate, an
      antioxidant-cytoprotective drug that enhances the gastric defensive barrier, the
      prevention of the secondary aggression induced by free radicals was more
      important.

PMID- 1392019
TI  - Dietary fats and inflammatory bowel disease in Asians.
AB  - Chemically processed, hydrogenated fats, such as margarine, have been implicated
      in the aetiology of inflammatory bowel disease. Toxic by-products may occur in
      their production or during frying and cooking. A survey of dietary oil usage was
      conducted among Asians in Leicester, comparing inflammatory bowel disease
      patients with healthy controls. Two groups were comparable for age, sex,
      religion, place of birth, number of years spent in Britain and vegetarian status.
      There were no significant differences in actual oils used between healthy
      controls and patients with ulcerative colitis or Crohn's disease (chi 2 = 0.142
      and 1.803 respectively, p greater than 0.50). However patients with Crohn's
      disease were found to recycle their cooking oil significantly more often than age
      and sex-matched colitics (p less than 0.05) and particularly age and sex-matched
      controls (p less than 0.01). A similar study needs to be conducted in India where
      the incidence of inflammatory bowel disease is low. If this difference is
      confirmed a programme of health education in cooking habits could lower the
      incidence of Crohn's disease.

PMID- 1392020
TI  - The association of Helicobacter pylori infection with low levels of urea and pH
      in the gastric juices.
AB  - Fifty-four gastric biopsies and their relative gastric juices were analyzed for
      the presence of Helicobacter pylori with both cultural and microscopic methods.
      Thirty-one samples were positive and twenty-three were negative. These data were
      therefore employed as references for the subsequent comparisons. Furthermore, the
      gastric juices were later tested to establish the urea concentration and the pH
      level. In addition, the sediment obtained after centrifugation was
      microscopically observed for the possible presence of other bacterial flora in
      the sample (unstained smears). The urease test on the bioptic specimens has also
      been evaluated. The presence of H pylori was strictly related to urea levels of
      less than 15 mg/dl and pH less than 3.5. Furthermore, H pylori was generally not
      associated with the presence of other bacterial flora (only 1 out of 12 samples).
      The latter instead, was almost exclusively present in high pH samples (with the
      exception of one). On the basis of these results, a simple diagnostic scheme was
      constructed to identify carrier subjects. All patients (14/14) with urea levels
      of more than 15 mg/dl were found to be negative as well as those presenting a pH
      of more than 3.5 (7/9) or evidence of other bacteria in the juices (8/9). The
      remaining subjects (30/31 or 29/31, respectively) presented H pylori in the
      gastric juices. The final classification was 96.3% (or 94.4%) correct.

PMID- 1392021
TI  - Microscopic colitis: can it be qualitatively and quantitatively characterized?
AB  - This study reports the histological features helpful in diagnosing microscopic
      colitis. Rectal biopsy specimens from 14 patients with microscopic colitis, 14
      with active ulcerative colitis and 14 without colonic inflammation were pooled
      and then assessed by three observers according to a predetermined protocol. Inter
      observer agreement was good except for Paneth cell metaplasia and endocrine cell
      metaplasia. Compared with healthy tissue, microscopic colitis showed a
      significant (p less than 0.05) increase in chronic inflammatory cells and a
      depletion of goblet cells but these changes were less pronounced than those seen
      in ulcerative colitis (p less than 0.05). In contrast to ulcerative colitis,
      microscopic colitis was associated with a more marked infiltration with
      eosinophils and an increase in intra-epithelial lymphocytes. These results show
      that microscopic colitis can be distinguished both from normal colonic tissue and
      from ulcerative colitis.

PMID- 1392022
TI  - Effect of alpha-gliadin-derived peptides from bread and durum wheat on K562(S)
      cells.
AB  - Previous studies suggested that the proteins and peptides that are responsible
      for coeliac small intestinal lesions, are also able to agglutinate K562(S) cells.
      On the contrary, peptides from whole gliadins from durum (tetraploid) wheat do
      not agglutinate these cells. Bread wheat alpha-gliadins have been identified as a
      major toxic fraction in coeliac disease. In the present research, alpha-gliadins
      were purified from durum and bread wheat cultivars. alpha-gliadin peptides from
      bread wheat were active in agglutinating K562(S) cells, whereas alpha-gliadin
      from durum wheat failed to induce any agglutinating activity. These results
      suggest that the lack of toxicity of gliadin from durum wheat cultivars is not
      related to a low content of alpha-gliadins but is mainly due to intrinsic
      structural differences from bread wheat gliadins.

PMID- 1392023
TI  - Double blind trial of colloidal bismuth subcitrate versus placebo in Helicobacter
      pylori positive patients with non-ulcer dyspepsia.
AB  - We have carried out a double blind placebo controlled trial to assess the effects
      of treatment with colloidal bismuth subcitrate in Helicobacter pylori associated
      non-ulcer dyspepsia. Eighty patients with dyspepsia, normal upper
      gastrointestinal appearances at endoscopy and H pylori associated active chronic
      gastritis on histology of gastric antral biopsies were included in the trial. The
      patients were randomised to receive colloidal bismuth subcitrate 240mg twice
      daily for four weeks or matching placebo and were reassessed four weeks after
      completing treatment. Twenty-six patients (67%) receiving colloidal bismuth
      subcitrate had normal histology or improved inflammation compared with five (13%)
      receiving placebo (p less than 0.001), and symptoms were absent or improved in 32
      (82%) and two (5%) respectively (p less than 0.001). Serum IgG level was a marker
      of infection, and fell with successful treatment. Colloidal bismuth subcitrate is
      effective treatment for H pylori associated non-ulcer dyspepsia with improved
      gastric antral histological appearances and has a beneficial effect on symptoms.

PMID- 1392024
TI  - "Oesophageal angina" in patients with angina pectoris: a possible side effect of
      chronic therapy with nitroderivates and Ca-antagonists.
AB  - The study was carried out on 18 patients with angina pectoris in whom the usual
      treatment with nitroderivatives and/or Ca-antagonists did not improve or prevent
      the angina-like chest pain in the absence of unstable angina. The patients
      underwent the following oesophageal examinations: X-ray, endoscopy-biopsy,
      manometry, acid perfusion test and 24-hour oesophageal pH ambulatory monitoring,
      the latter two being made in association with dynamic ECG. The presence of
      coronary insufficiency had been previously determined by means of ECG and
      scintigraphic stress tests and, when necessary, coronary arteriography was
      performed. In 10/18 patients severe oesophageal motor disorders were observed,
      the most frequent being diffuse oesophageal spasm. In the entire group the lower
      oesophageal sphincter basal tone was significantly lower than normal. In 14/18
      patients a pathologic gastroesophageal reflux was detected: in 2 of these
      patients a temporal correlation between pain attacks and episodes of
      gastroesophageal reflux were observed in the absence of ECG modifications. Acid
      perfusion test induced the angina-like chest pain in another 2 patients without
      ECG modifications. In conclusion, the angina-like chest pain of these patients is
      not due to a failure of the antianginal therapy in relieving the coronary
      insufficiency, but is most probably related to gastroesophageal reflux. This
      oesophageal disorder may be considered a side effect caused by prolonged therapy
      with nitroderivatives and Ca-antagonists. In fact, these drugs decrease the lower
      oesophageal sphincter tone which is the main barrier against the reflux of
      gastric contents into the oesophagus so favoring gastroesophageal reflux and
      related disorders, including oesophageal pain.

PMID- 1392025
TI  - Risk factors and association with HBV infection in chronic C hepatitis.
AB  - The route of transmission in more than 50% of the patients with hepatitis C virus
      (HCV) infection is unknown. Only a minority of patients have had a previous blood
      transfusion; sporadic spread seems to be much more important, although the role
      of inapparent parenteral exposure is yet to be established. Aim of this study was
      to investigate if a relationship exists between history for exposure to known
      risk factors, concurrent HBV status and histological findings (presence of
      cirrhosis) in patients with chronic HCV liver disease. We studied 86 subjects
      with chronic HCV liver disease, subdivided according to their HBV status. Fifty
      four patients were anti-HBV negative; in the remaining 32 subjects, antibodies to
      HBV were found. Our data show that: 1) history for exposure to known risk factors
      is more likely to be present in patients with chronic HCV liver disease and
      concurrent positivity for antibodies to HBV than in anti-HCV positive patients
      without HBV antibodies (62.5% vs 38.9%); and 2) the incidence of liver cirrhosis
      is higher in anti-HCV positive patients with anti-HBV antibodies than in
      exclusively anti-HCV positive patients (56.2% vs 12.9%). We conclude that the
      association of history for exposure to known risk factors and anti-HBV positivity
      could be a marker of progression from mild to severe liver damage in patients
      with chronic HCV liver disease (i.e. in the absence of both identifiable risk
      factors and HBV antibodies, HCV infection could have a less severe clinical
      outcome). Therefore, in these patients a closer follow-up and earlier interferon
      therapy are probably needed.

PMID- 1392027
TI  - Splenic torsion: a rare cause of splenomegaly.
AB  - The authors report a rare case of splenomegaly, caused by recurring splenic
      torsion in a 31-year-old patient. On the basis of this experience and literature
      data, pathogenetic, symptomatological, diagnostic and therapeutic aspects are
      discussed. Analysis of the clinical history and diagnostic procedures confirm the
      difficulty in ascertaining this condition preoperatively. In any case, splenic
      torsion should be considered in the differential diagnosis of painful
      splenomegalies.

PMID- 1392026
TI  - Coeliac disease and collagenous colitis.
AB  - A thirteen and a half year old girl and her father were both investigated because
      of chronic watery diarrhoea and growth failure or weight loss. Both were
      diagnosed as having coeliac disease. In the daughter, collagenous colitis was
      also diagnosed. The father had colonic collagen deposition with inflammatory
      changes as well. Both improved on gluten-free diets, but colonic collagen
      deposition persisted.

PMID- 1392028
TI  - ["Karoshi" and causal relationships].
AB  - This paper aims to introduce a measure for use by physicians for stating the
      degree of probable causal relationship for "Karoshi", ie, a sudden death from
      cerebrovascular diseases or ischemic heart diseases under occupational stresses,
      as well as to give a brief description for legal procedures associated with
      worker's compensation and civil trial in Japan. It is a well-used measure in
      epidemiology, "attributable risk percent (AR%)", which can be applied to describe
      the extent of contribution to "Karoshi" of the excess occupational burdens the
      deceased worker was forced to bear. Although several standards such as average
      occupational burdens for the worker, average occupational burdens for an ordinary
      worker, burdens in a nonoccupational life, and a complete rest, might be
      considered for the AR% estimation, the average occupational burdens for an
      ordinary worker should normally be utilized as a standard for worker's
      compensation. The adoption of AR% could be helpful for courts to make a
      consistent judgement whether "Karoshi" cases are compensatable or not.

PMID- 1392029
TI  - [Factors affecting the increase in hospitalized medical care expenditure in
      Japan: analysis of national data in all 47 prefectures].
AB  - To clarify factors affecting the increase in annual expenditure for hospitalized
      medical care in Japan, the effects of the following four variables in all 47
      prefectures were analyzed: (1) the hospitalized medical care expenditure per day
      per inpatient, (2) the number of admissions per population base, (3) average
      length of stay of patients in hospital per year and (4) the number of hospital
      beds per population base. The annual expenditure for hospitalized medical care
      per population base was correlated most significantly with the number of hospital
      beds per population base. The annual expenditure was also significantly
      correlated positively with the number of admissions per population base and
      average length of stay of patients in hospital per year, and inversely with the
      hospitalized medical care expenditure per day per inpatient. Hospitalized medical
      care expenditure per day per inpatient was inversely correlated with average
      length of stay of patients in hospital and the number of hospital bed per
      population base. Results from stepwise multiple regression analysis indicated
      that the number of hospital bed per population base and the hospitalized medical
      care expenditure per day per inpatient are the only two variables which have
      significant effects on the annual expenditure for hospitalized medical care per
      population base. The annual rate of increase for annual expenditure for
      hospitalized medical care per population base from 1980 to 1986 was 6.1%.
      Similarly, the rate of increase in the hospitalized medical care expenditure per
      day per inpatient was 3.5%; that of the number of admissions per population base
      was 3.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392030
TI  - [Predictors of the development of hypertension: ten-year follow-up study in a
      community].
AB  - Predictors of the development of hypertension were examined in a 10-year follow
      up study of normotensive Japanese adults. Subjects (n = 265), aged 30-69 years at
      entry, normotensive and with no past history of antihypertensive treatment at
      entry, were studied in terms of the relationship of various physical,
      biochemical, dietary, and lifestyle data to the subsequent development of
      hypertension (defined as systolic blood pressure (SBP) more than 140 mmHg and/or
      diastolic blood pressure (DBP) more than 90 mmHg and/or starting antihypertensive
      treatment) with analysis accomplished using univariate and multivariate life
      table methods. Univariate analyses by the generalized Wilcoxon test showed
      significantly higher incidence of hypertension in those subjects with SBP 120
      mmHg or more (p < 0.001), DBP 75 mmHg or more (p < 0.001), serum glutamate
      oxaloacetate transaminase (GOT) 20 KU or more (p < 0.001), serum glutamate
      pyruvate transaminase (GPT) 15 KU or more (p < 0.001), serum gamma-glutamyl
      transpeptidase (gamma-GTP) 10 IU/l or more (p < 0.001), age 50 or older (p =
      0.002), body mass index 22 kg/m2 or more (p = 0.012), and serum creatinine less
      than 1.2 mg/dl (p = 0.020) than in the other subjects. Multivariate analysis by
      the Cox proportional hazards model confirmed that relatively higher SBP (p <
      0.001), lower serum creatinine (p < 0.001), higher gamma-GTP (p = 0.002), and
      higher age (p = 0.041) were independent and significant predictors of future
      hypertension.

PMID- 1392031
TI  - [A study of the mentally ill in institutions for homeless people in Tokyo].
AB  - Homeless problems associated with poverty may be considered almost resolved in
      Japan because of the post World War II economic development, but in large cities
      such as Tokyo the homeless are still being produced, a reflection of a variety of
      social problems. This study is based on an analysis of admission records of an
      institution for the homeless which was established in 1952 in Tokyo. Subjects are
      2,122 single persons who were admitted between 1952 and 1985. Among these, 136
      are mentally ill persons, who are the main subjects of analysis in this study.
      Results show that, which after 1970 the number of the mentally ill significantly
      increased, many of those people dropped out of the institution mostly because
      they were originally admitted directly from discharge from hospitals because
      there was no other place to go except the institutions, and also because the
      institution, originally meant to house street people who had been detained, did
      not offer appropriate programs for the mentally ill. A solution to these problems
      requires that roles of institutions for the homeless and subjects admitted be
      reconsidered. Institution staff should enrich programs designed for the homeless
      mentally ill and help them organize their social network and live in the
      community.

PMID- 1392032
TI  - [Reliability of a long-term recall method of dietary survey].
AB  - A total of 493 male inpatients were subjects in a study of the dietary intake
      (food frequency) when they were elementary school age and at the time of marriage
      by a long-term recall method. In order to examine the reliability of the recalled
      dietary data, 21 food items were compared with results of the National Nutrition
      Survey for the same time period. Food intake by the long-term recall method,
      especially meats, egg, milk and rice correlated well with the results of the
      National Nutrition Survey. From these results it appears that long-term recall of
      dietary intake frequency data averages are similar to the results of the National
      Survey data. Therefore the long-term recall method reflects the dietary practices
      of that era, and keeping in mind its limitations, its use as a means of revealing
      the dietary practices of a population is suggested.

PMID- 1392033
TI  - [A study on patients utilizing 'rehabilitation' at the community level--special
      characteristics of patients without stroke].

PMID- 1392034
TI  - [Comparison of physical conditions between urban and rural populations by
      Japanese weight and height standards for estimating over and underweight].

PMID- 1392035
TI  - Attributing preferences and violating neutrality.

PMID- 1392036
TI  - The boundaries of the persistent vegetative state.

PMID- 1392037
TI  - Brain death and slippery slopes.

PMID- 1392038
TI  - Awakening: bad news and good news.

PMID- 1392039
TI  - Permanently locked-in syndrome in the neurologically impaired neonate: report of
      a case of Werdnig-Hoffmann disease.

PMID- 1392040
TI  - Locked-in syndrome and ethics committee deliberation.

PMID- 1392041
TI  - Abating treatment in the NICU.

PMID- 1392042
TI  - Compassion, consensus, and conflict: should caregivers' needs influence the
      ethical dialectic?
AB  - There are three important principles to be derived from this case. First, it is
      essential not to confound the technical problem of assessing pain and suffering
      with the ethical issue of judgments about pain and suffering. Second, in most
      cases, the apparent limitations of traditional ethical theory in critical care
      decisions are precisely that: apparent limitations only. The alternatives,
      especially intuitionism, are far more troublesome. Finally, the claim of health
      care workers to be professionals places legitimate constraints on the extent to
      which they may be permitted to have their needs and wants influence the ethical
      dialectic. The achievement and maintenance of "comfortable, compatible
      relationships" cannot be legitimately construed as a major objective of
      biomedical ethics--although one would hope it will become a cherished, if
      serendipitous, byproduct. In short, paraphrasing (and reversing) Archibald
      MacLeish on poetry: Ethics should not be/but mean.

PMID- 1392043
TI  - The physician, the family, and the truth.

PMID- 1392044
TI  - On grinding axes and examining practices.

PMID- 1392045
TI  - Consent, ethics, and community.

PMID- 1392046
TI  - Ignorance and altruism.

PMID- 1392047
TI  - A response to a purported ethical difficulty with randomized clinical trials
      involving cancer patients.

PMID- 1392048
TI  - The microethics and macroethics of hospital abortion committees.

PMID- 1392049
TI  - Abortion: doomed only to an immoderate response?

PMID- 1392050
TI  - Commentary on "a perinatal ethics committee on abortion".

PMID- 1392052
TI  - "Cost accounting of safeguards in life equivalents" is a better title.

PMID- 1392051
TI  - Legal trends in bioethics.

PMID- 1392053
TI  - Euthanasia: still open for debate.

PMID- 1392054
TI  - A sensitive and relevant model for evaluating anti-inflammatory activity-papaya
      latex-induced rat paw inflammation.
AB  - A new model employing latex of papaya as an inflammagen has been developed for
      testing anti-inflammatory activity. The latex (exudate) was harvested from the
      unripe papaya fruit, which had been dried under vacuum. The latex was then
      suspended in 0.05 M sodium acetate buffer. This suspension when injected in rat
      hind paw produced concentration-dependent inflammation. Of the 0.25% of this
      suspension, 0.1 ml was found ideal for evaluating anti-inflammatory activity of
      test drugs. This concentration produced 70%-100% inflammation lasting for about 5
      hr with a maximum effect at h 3. The test drugs employed were prednisolone,
      aspirin, indomethacin, phenylbutazone, ibuprofen, piroxicam, chloroquine,
      levamisole, and a mixture of boswellic acids. For comparison, these drugs were
      also tested against carrageenan-induced inflammation. All the test drugs-
      steroidal, aspirin, and non-aspirin-like--showed anti-inflammatory activity
      against latex-induced inflammation. The activity of chloroquine, levamisole, and
      boswellic acids was significantly more against latex as compared with that of the
      carrageenan model. The inflammation caused by latex may be attributed to both its
      hydrolytic enzymes--papain and chymopapain--and glutathione, the activator of
      these enzymes. These enzymes seem to act like lysosomal enzymes that are released
      in inflammatory disease processes which mediate inflammation by stimulating the
      synthesis of prostaglandins. The papaya latex-induced inflammation model appears
      to be a sensitive, broad-based, and relevant one likely to prove useful for
      discovering new and effective drugs against inflammation and rheumatoid
      arthritis.

PMID- 1392055
TI  - A freely moving and behaving rat model for the chronic and simultaneous study of
      drug pharmacokinetics (blood) and neuropharmacokinetics (cerebrospinal fluid):
      hematological and biochemical characterization and kinetic evaluation using
      carbamazepine.
AB  - A freely moving and behaving rat model for the chronic and simultaneous study of
      drug pharmacokinetics (blood) and neuropharmacokinetics [cerebrospinal fluid
      (CSF)] is described. The blood (jugular vein) and CSF (cisterna magna) catheters
      employed are simple, reliable, and inexpensive. The blood catheter was made of
      soft and flexible Silastic tubing and sealed with heparin. The CSF catheter
      consisted of intersliding polythene tubing and interlocking Silastic tubing,
      which allowed maneuverability within the cisternal magna space and thus
      prolonging patency for chronic studies. Both catheters were well tolerated by the
      animals, and the postoperative success rate was 80%-100%; after 8 days 80%-85% of
      catheters were still patent. Using a sampling protocol considered suitable for
      kinetic studies, we determined numerous biochemical and hematological parameters
      and compared them with those values obtained postsurgically and in control rats.
      The parameter changes associated with the sampling protocol did not affect the
      kinetics of the commonly prescribed antiepileptic drug carbamazepine and its
      primary pharmacologically active metabolite carbamazepine-10, 11-epoxide.
      Therefore, the model can be used to study the interrelationship between drug
      kinetics at central and peripheral sampling sites and mechanism(s) of drug
      action.

PMID- 1392056
TI  - The perfused human bronchiolar tube characteristics of a new model.
AB  - Strips or rings of airway tissue are often used to study contractile responses of
      human airways in vitro. These preparations have the disadvantage that it is
      impossible to deliver stimuli selectively to the mucosal or serosal surface.
      Hence, they allow only for a limited evaluation of the modulatory role of the
      airway epithelium. We developed an in vitro model that allows independent
      stimulation from either the serosal or the mucosal side of human peripheral
      airways. Segments of human peripheral airways were perfused with a Krebs solution
      at a constant pressure, and responsiveness was measured as a change in flow rate.
      Pressure/flow relationships indicated laminar flow over a wide pressure range,
      and a working pressure of 6 cm H2O was chosen because this is a physiological
      transpulmonary pressure. When stepwise stretching the airway to 180% of its
      length, we noted an increase in baseline flow and a decrease in flow reduction
      after methacholine 10(-5) M. At 140% of the length, accurate and reproducible
      measurements of the sensitivity (EC50) to methacholine were obtained, and airway
      closure did not occur. A one-way analysis of variance (ANOVA) revealed that the
      between-patients differences accounted for 91% of the total variability for -log
      EC50. We conclude that this in vitro model offers interesting possibilities for
      evaluating the modulatory effects of the human airway epithelium. In addition,
      the model provides the opportunity to study human small-airway mechanical
      properties and secretory functions.

PMID- 1392057
TI  - Responses of isolated rabbit thoracic aortae to endothelin-1 and several
      vasoactive substances. A new blood perfusion circuit under the controlled
      conditions of resistance and flow.
AB  - Analysis of the reactivity of isolated rabbit thoracic aorta to isoproterenol and
      norepinephrine injected into a blood perfusion circuit intraarterially (i.a.)
      under controlled conditions of resistance and flow using conscious support
      rabbits revealed that with pressure loads of 10-20 mmHg for a vessel-holding
      chamber and 60 mmHg for a Starling pneumatic resistance set, a suitable
      vasodilation or vasoconstriction can be obtained. This leads us to assume that
      the system could be used to assess the direct influence of vasoactive substances
      on vasomotor tone and, furthermore, the support rabbit could be used for systemic
      hemodynamic variables and behavior observation. The i.a. injection of increasing
      doses of endothelin-1 (ET) (0.01-0.3 microgram) caused a weak but long-lasting
      and dose-dependent vasoconstriction of the thoracic aorta; its effect was less
      potent than that of angiotensin II or norepinephrine when their peak responses
      were compared. The duration of vasoconstriction caused by 0.3 microgram i.a. of
      ET was approximately 30 min and much longer than that of angiotensin II and
      norepinephrine. Histamine, serotonin, and prostaglandin E2 produced noticeable
      dose-dependent vasoconstriction. When ET (0.1-3 micrograms) was injected i.v. to
      conscious rabbits, the systemic blood pressure, which first dropped and then
      rose, was accompanied by significant changes in the heart rate in a reciprocal
      way. The observed rise in the blood pressure with the accompanying decrease in
      the heart rate lasted for at least 30 min following 1 microgram i.v. of
      ET.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392058
TI  - A simple T-maze method for estimating working memory in mice. Effect of
      ethylcholine mustard aziridinium ion (AF64A).
AB  - Mice were housed in a cage containing a T maze. A watering place was located at
      the entrance of the maze. The right and left arms of the maze each had two exits,
      one of which led to the home cage where food was placed, while the other led to
      the watering place via a bypass. The exit leading to the home cage in either the
      right or left arm was alternately closed every 90 min. One-way swinging doors
      were inserted at the entrance to each arm and between each bypass and the
      watering place. The mice were given a cholinergic neurotoxin--ethylcholine
      mustard aziridinium ion (AF64A)--(8 nmol) or saline as a control into the left
      ventricle 2 weeks before they were housed in the apparatus. Those mice housed in
      this apparatus mastered the alternation task at a 5-sec delay on day 3 in the
      sham group and on day 4 in the AF64A group. When a longer delay (5-90 sec) was
      introduced for the mice that mastered the alternation task at 5-sec delay, the
      AF64A group made significantly more errors than did the sham group at 60- and 90
      sec delays. These results show that the apparatus is useful in estimating working
      memory in mice with little effort.

PMID- 1392059
TI  - Computer system for the acquisition and analysis of vascular contractility.
      Application to a bioassay of endothelial cell function.
AB  - A system for the digital acquisition and subsequent analysis of the tension
      developed by isolated blood vessels in response to an endothelial cell
      superfusate is reported. Tension of the isolated rat aortic rings was measured by
      strain gauge. Strain-gauge output was then amplified, and the analog signal was
      digitized on a 16-channel A/D board. Lab tech Notebook software was used to
      display and store the data. The sampling rate was 0.1 Hz, and the data was
      written concurrently to hard disk and printer. Both disk and printer output were
      accompanied by a time stamp for subsequent ease of retrieval. The endothelial
      cell bioassay system allowed measurement of changes in vascular tension after the
      release of endothelium-dependent relaxing factor, nitric oxide (EDRF-NO) from
      cultured cells. Cells were cultured on microcarrier beads, formed into columns,
      and perfused with physiological salt solution. Significant (p < 0.05) relaxant
      responses occurred after agonist stimulation with bradykinin (10(-8) M; Emax 
      31.0% +/- 8.2%), acetylcholine (10(-8) M; Emax -33.2% +/- 5.0%), and calcium
      ionophore A 23187 (10(-6) M; Emax -55.7% +/- 15.4%). These responses were
      dependent on EDRF-NO, as shown by both the lack of relaxation in the absence of
      endothelial cells, and that relaxation to A 23187 was overcome by hemoglobin (3 x
      10(-6) M). Results were manipulated graphically to allow the superimposition of
      data and thereby provide a mean and standard error of the mean for the entire
      time course of each response. Thus, a system was produced where fidelity of data
      expression was not dependent on measurements made at single points, but on the
      sampling frequency of the acquisition system.

PMID- 1392060
TI  - The influence of vancomycin concentration and the pH of plasma on vancomycin
      protein binding.
AB  - A review of numerous studies of the protein binding of vancomycin suggests major
      discrepancies among their results. The reported percent protein binding of
      vancomycin varies from 0% to 98%. The influence of pH and concentration on the
      protein binding of vancomycin was investigated in this study. There was a
      significant difference (p < 0.001) in percent protein binding in vancomycin
      spiked plasma samples across the pH range of 7.0-8.0. There was no significant
      difference (p > 0.05) in percent protein binding in vancomycin-spiked plasma
      samples across the concentration range of 2-80 mg/L. It is likely that some of
      the variation reported to date may be due to a lack of control of pH during the
      measurement of protein binding of vancomycin.

PMID- 1392061
TI  - Quantitative colorimetric assay for basic fibroblast growth factor using bovine
      endothelial cells and heparin.
AB  - An accurate and reproducible colorimetric assay was established to determine the
      concentration of basic fibroblast growth factor (bFGF) or bFGF-like activity in
      culture media and biological fluids. Fetal bovine heart endothelial cell line
      ATCC CRL 1395 was used as the bFGF-dependent cell line. The proliferation
      stimulating activity of bFGF was determined by measuring the amount of formazan
      formed by the mitochondrial enzymes from a tetrazolium salt, 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), instead of counting
      the viable cell numbers or measuring the incorporation of [3H]-thymidine. The
      addition of 250 ng/mL of heparin to the culture medium resulted in about a
      tenfold increase in the proliferation-stimulating activity of bFGF and allowed
      the detection of as low as 10 pg/mL of bFGF. Heparin also resulted in much
      smaller inter- and intraassay variations. The bFGF concentrations determined by
      this colorimetric assay correlated well with those determined by both the [3H]
      thymidine incorporation assay using BALB/c 3T3 fibroblast cells (r = 0.998) and
      the cell number count assay (r = 0.996). This assay can be adapted to quantify
      bFGF or bFGF-like activity in tissue culture media and biological fluids such as
      plasma and organ extracts.

PMID- 1392062
TI  - Fine structure of olfactory epithelia of gastropod molluscs.
AB  - Among gastropod molluscs the chemical senses are most important for location of
      distant objects. They are used in food finding, locating mates, avoiding
      predators, trail following, and homing. Chemoreceptors are commonly associated
      with the oral area, the tentacles, and the osphradium, which lies in the mantle
      cavity. Most chemosensory neurons are primary sensory neurons, although secondary
      sensory cells have been reported in the osphradium of some prosobranch
      gastropods. Most chemosensory organs contain sensory cells with ciliated sensory
      endings that are in contact with the external environment. Some sensory endings
      have only microvilli or have no surface elaborations. Cilia on sensory endings
      are commonly of the conventional type, but some species have modified cilia; some
      lack rootlets, some have an abnormal microtubular content, and some have paddle
      shaped endings. The perikarya of sensory neurons may be within the sensory
      epithelium, below it, or in ganglia near the sensory surface. In some groups of
      gastropods there are peripheral ganglia in the olfactory pathway; in others
      chemosensory axons appear to pass directly to the CNS. Olfactory epithelia of
      terrestrial pulmonates have modified brush borders with long branching plasmatic
      processes and a spongy layer of cytoplasmic tubules which extend from the
      epithelial cells. Sensory endings of the olfactory receptors are entirely within
      this spongy layer. Aquatic pulmonates may have a similar spongy layer in their
      olfactory epithelia, but the cilia of sensory endings, as well as motile cilia of
      epithelial cells, extend well beyond the spongy layer.

PMID- 1392063
TI  - The aesthetasc concept: structural variations of putative olfactory receptor cell
      complexes in Crustacea.
AB  - The structure of the aesthetascs has been investigated in the prawn Macrobrachium
      rosenbergii (larvae and juveniles), the opossum shrimp Neomysis integer, the
      euphausid Meganyctiphanes, and in the water-fleas Daphnia magna and D.
      longispina. The aesthetascs, that are thought to represent olfactory receptors,
      exhibit a considerable structural variation, ranging from the well known
      aesthetascs of higher crustaceans (lobster, crab, crayfish) to the corresponding
      sensilla found in the water-fleas and the males of opossum shrimps. The two
      following morphological characteristics of the aesthetascs are thought to
      indicate an olfactory function: the shape of the cuticular hair that is long and
      essentially hose-shaped, and the thin, loosely arranged cuticle of at least the
      outer part of the cuticular hair. The presence of other structural elements such
      as sensory cells, cilia, and enveloping cells are vital for the olfactory
      function, but the development is variable, which makes their use in the
      morphological definition of aesthetascs problematic.

PMID- 1392065
TI  - Fine structure of a developing insect olfactory organ: morphogenesis of the
      silkmoth antenna.
AB  - The olfactory organ of the silkmoth Antheraea polyphemus is the feathered antenna
      which carries about 70,000 olfactory sensilla in the male. It develops within 3
      weeks from a leaf-shaped epidermal sac by means of segmental primary and
      secondary indentations which proceed from the periphery towards the centerline.
      During the first day post-apolysis, the antennal epidermis differentiates into
      segmentally arranged, alternating sensillogenic and non-sensillogenic regions.
      Within the first 2 days post-apolysis, the anlagen of olfactory sensilla arise
      from electron-dense mother cells in the sensillogenic epidermis. The axons of the
      developing sensilla begin to form the primary innervation pattern during the
      second day. The sensilla develop approximately within the first 10 days to their
      final shape, while the indentations are completed during the same period of time.
      The indentations are most probably driven by long basal extensions of epidermal
      cells, the epidermal feet. Primary indentations follow the course of segmentally
      arranged tracheal bundles and form the segments of the antenna. The secondary
      indentations follow the course of the primary segmental nerves which are
      reconstructed by this process. During the remaining time of development, the
      cuticle of the antenna and the sensory hairs is secreted by the epidermal and the
      hair-forming cells.

PMID- 1392064
TI  - Experimental morphology of insect olfaction: tracer studies, X-ray microanalysis,
      autoradiography, and immunocytochemistry with silkmoth antennae.
AB  - The general morphology and methodological peculiarities of insect sensilla are
      briefly reviewed. The stimulus conducting pore-tubule systems of pheromone
      sensitive sensilla of the silkmoths Bombyx mori and Antheraea polyphemus are
      described. Lipophilic tracers readily enter the hair lumen, while hydrophilic
      tracers do so only after prolonged extraction with lipid solvents and/or pronase.
      X-ray microanalysis demonstrates a high potassium content of the sensillum lymph;
      calcium was only found in the haemolymph above detection limit. Auxiliary cells
      rapidly take up radioactive leucine administered via the haemolymph. Antibodies
      against pheromone-binding protein of Antheraea polyphemus label the sensillum
      lymph of sensilla trichodea, but not of sensilla basiconica in A. polyphemus as
      well as in B. mori. The cytoplasm of auxiliary cells of the sensilla trichodea is
      also labelled. The results are discussed in context with present hypotheses on
      the role of sensillum lymph in stimulus transport and inactivation.

PMID- 1392066
TI  - Fine structure of olfactory sensilla in myriapods and arachnids.
AB  - Structural features of various types of olfactory sensilla are reviewed. 1)
      Sensilla basiconica which differ in form and size are found on the antennae of
      centipedes and millipedes. Their walls show longitudinal slits or grooves that
      either open into the sensillum lumen or do not penetrate the cuticle. In other
      such sensilla the outer surface is pierced by pores and the inner surface grooved
      and pocketed. These sensilla are innervated by one to six sensory cells. Their
      unbranched outer dendritic segments extend to the tip of the sensillum. The
      sensory cells are surrounded by two or three sheath cells which terminate at the
      sensillum base or form a continuous tube around the entire length of the outer
      dendritic segments. 2) Temporal organs of centipedes are located between the
      insertion of the antenna and the ocelli. These sensilla consist of a shallow
      cuticular ring with a central sensory plate made up by a layer of unperforated
      cuticle or a capsule with a mushroom-shaped structure inside formed by fibrous
      looking cuticle. A dozen sensory cells with unbranched outer dendritic segments
      innervate each sensillum. They extend toward the sensory cuticle and pass just
      below it. Numerous sheath cell processes run parallel to the outer dendritic
      segments up to the sensory cuticle. 3) Thread-like flagella of Pauropoda are
      found on the antennae. They possess a flexible unperforated cuticular wall. These
      sensilla contain nine sensory cells surrounded by several sheath cells which form
      a continuous cytoplasmic tube around the outer dendritic segments. 4) Single
      walled sensilla with numerous plugged pores penetrating the cuticular wall occur
      on the tarsus of the first leg in ticks. Each sensillum is innervated by 4-15
      sensory cells. Three sheath cells terminate in the base of the sensillum. 5)
      Double-walled sensilla with spoke canals are found on the first tarsus of ticks.
      Their shaft is longitudinally grooved. Pore canals lead inward from the bottom of
      the grooves and open into vase-shaped chambers. From its base these canals extend
      into the lumen of the sensillum which contains unbranched outer dendritic
      segments of 1-2 sensory cells. 6) Single-walled sensilla with pore openings occur
      on the distal tarsal segments of the first leg of whip spiders. These sensilla
      are innervated by 40-45 sensory cells. Their unbranched outer dendritic segments
      fill the shaft lumen and extend partly into the wall pores. Microvillus-shaped
      sheath cell processes line the inner surface of the cuticular wall.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1392067
TI  - Hapten-tagged plasma proteins as immunocytochemical probes for the study of
      vascular permeability.
AB  - Bovine serum albumin and transferrin were covalently coupled with fluorescein
      isothiocyanate and digoxigenin, respectively, and intravenously co-injected in
      equal amounts in mouse. The derivation of the two proteins induces minor
      alterations of their physicochemical properties as well as of their physiological
      functions. The two tracers were revealed within vascular and extravascular
      compartments of diaphragm by quantitative postembedding immunocytochemistry,
      using antibodies against each of the haptens in conjunction with the protein AG
      gold complexes. The influence of different fixatives and embedding protocols on
      the immunodetectability of the hapten-tagged proteins was assessed. Both resist
      reasonably well to osmication and embedding in Epon. None of the haptens reacted
      with the heterologous antibody. At 30 minutes after injection, the tracers were
      detected in blood plasma, interstitium, and endothelial plasmalemmal vesicles.
      The presence of both proteins within the interendothelial clefts was
      inconspicuous. The ratios between the labeling densities found over endothelium,
      interstitial space, and vascular lumen were similar for both tracers. This
      suggests that the endothelium of mouse diaphragm capillaries might exhibit
      comparable permeabilities towards serum albumin and transferrin which are similar
      in size and charge. The study shows that hapten-tagged polypeptides are close to
      the corresponding native macromolecules, and represent interesting tools for the
      morphological study of dynamic processes such as transcytosis.

PMID- 1392068
TI  - Phylogeny of the vomeronasal system and of receptor cell types in the olfactory
      and vomeronasal epithelia of vertebrates.
AB  - In this paper, the evolutionary origin of the vomeronasal system as a discrete
      sensory system separate from olfaction is examined. The presence of a discrete
      vomeronasal system appears to be a derived character in tetrapods, and its
      presence in larval amphibians indicates that the system did not arise as a
      terrestrial adaptation. The vomeronasal system has been lost independently in
      several taxa, including crocodilians, some bats, cetaceans, and some primates.
      The presence of microvillar receptor cells in the vomeronasal epithelium appears
      to be the ancestral condition for tetrapods, and alternative hypotheses
      concerning the ancestral condition for receptor cell types in the vertebrate
      olfactory epithelium are discussed. Finally, the possibility that the vomeronasal
      system is present in some fishes in a form that has not been recognized is
      discussed in relation to the phylogenetic distribution of receptor cell types in
      vertebrates.

PMID- 1392069
TI  - Ciliated and microvillar receptor cells degenerate and then differentiate in the
      olfactory epithelium of rainbow trout following olfactory nerve section.
AB  - We used scanning (SEM) and transmission (TEM) electron microscopy to examine
      ultrastructural changes in the olfactory epithelium (OE) of rainbow trout
      following unilateral olfactory nerve section. Both ciliated receptor cells (CRC)
      and microvillar receptor cells (MRC) degenerated and subsequently differentiated
      from unidentified precursor cells. The following changes took place in fish that
      were held at 10 degrees C at the stated period following olfactory nerve section:
      on day 7, MRC and CRC contained intracellular vacuoles; on day 12, the olfactory
      knobs appeared disrupted; by day 26, olfactory receptor cells were absent from
      the OE; on day 42, there were receptor cell bodies and a few CRC with short cilia
      at the apical surface; and on day 55, a small number of both CRC and MRC had
      differentiated. By day 76, both CRC and MRC repopulated the OE. Degenerative
      changes in the cytoplasm of the sustentacular cells (SC) and ciliated nonsensory
      cells (CNC) were observed in the first 26 days following olfactory nerve section,
      but these cells remained intact throughout the experiment. The degeneration and
      subsequent differentiation of CRC and MRC supports and extends previous
      observations that both cell types are olfactory receptor neurons with axons that
      extend along the olfactory nerve to the olfactory bulb.

PMID- 1392070
TI  - Ultrastructural neurobiology of the olfactory mucosa of the brown trout, Salmo
      trutta.
AB  - This paper describes four investigations of the olfactory mucosa of the brown
      trout: 1) the ultrastructure of the olfactory mucosa as revealed by scanning
      (SEM), conventional transmission (TEM), and high voltage (HVEM) electron
      microscopy; 2) light and electron-microscopic investigations of retrograde
      transport of the tracer macromolecule horseradish peroxidase (HRP) when applied
      to the cut olfactory nerve; 3) SEM and TEM investigations of the effects of
      olfactory nerve transection on cell populations within the olfactory epithelium;
      and 4) ultrastructural investigations of reversible degeneration of olfactory
      receptors caused by elevated copper concentrations. The trout olfactory
      epithelium contains five cell types: ciliated epithelial cells, ciliated
      olfactory receptor cells, microvillar olfactory receptor cells, supporting cells,
      and basal cells. The ciliated and microvillar olfactory receptor cells and a
      small number of basal cells are backfilled by HRP when the tracer is applied to
      the cut olfactory nerve. When the olfactory nerve is cut, both ciliated and
      microvillar olfactory receptor cells degenerate within 2 days and are
      morphologically intact again within 8 days. When wild trout are taken from their
      native stream and placed in tanks with elevated copper concentrations, ciliated
      and microvillar cells degenerate. Replacement of these trout into their stream of
      origin is followed by morphologic restoration of both types of olfactory receptor
      cells. Ciliated and microvillar receptor cells are primary sensory bipolar
      neurons whose dendrites make contact with the environment; their axons travel
      directly to the brain. Consequently, substances can be transported directly from
      the environment into the brain via these "naked neurons." Since fish cannot
      escape from the water in which they swim, and since that water may occasionally
      contain brain-toxic substances, the ability to close off--and later reopen--this
      anatomic gateway to the brain would confer a tremendous selective advantage upon
      animals that evolved the "brain-sparing" capacity to do so. Consequently, the
      unique regenerative powers of vertebrate olfactory receptor neurons may have
      their evolutionary origin in fishes.

PMID- 1392072
TI  - Olfactory epithelium in young adult and aging rats as seen with high-resolution
      scanning electron microscopy.
AB  - The present study uses mainly scanning electron microscopy to demonstrate the
      three-dimensional internal cell structures of rat olfactory epithelial cells. The
      aldehyde-prefixed osmium-DMSO-osmium (AODO) method devised by Tanaka and
      Mitsushima (1984) was applied to the present study to disclose intracellular
      structures such as endoplasmic reticulum, mitochondria, Golgi apparatus, and
      lysosomes. The spatial distribution pattern of these structures in olfactory and
      supporting cells is discussed, paying special attention to the formation of
      lipofuscin-like granules present in aged rats.

PMID- 1392071
TI  - Morphology of olfactory epithelium in humans and other vertebrates.
AB  - Human olfactory epithelium is similar in organization and cell morphology to that
      of most vertebrate species. The epithelium has a pseudostratified columnar
      organization and consists of olfactory neurons, supporting and basal cells. Near
      the mucosal surface there are also microvillar cells. These cells have neuron
      like features and may be chemoreceptors. Human olfactory epithelium is not a
      uniform sensory sheet. Patches of non-sensory tissue often appear in what was
      thought to be a purely olfactory region. The significance of these patches has
      not been determined, but they could reflect exposure to environment agents or
      changes that occur during the normal aging process. In order to better understand
      the human olfactory system, further knowledge of the normal structure is
      necessary. This review addresses the morphology of the human olfactory epithelium
      and the remarkable plasticity of the vertebrate olfactory system.

PMID- 1392073
TI  - The human primary olfactory pathway: fine structural and cytochemical aspects
      during development and in adults.
AB  - Despite increasing knowledge about the biophysiology of the human olfactory
      system, understanding of the development of this pathway in humans lags
      considerably behind that of other vertebrates. Developmental studies have largely
      concentrated on the generation of cell types in the olfactory epithelium during
      the first trimester, while detailed ultrastructural observations usually describe
      the adult morphology. In this review, we have shown that contrary to what has
      been generally assumed, the surface of the human olfactory epithelium is
      heterogeneous and that its olfactory nerves differ ultrastructurally from those
      of other vertebrates studied. The development of the human primary olfactory
      pathway is discussed in terms of the appearance of olfactory bulb laminae,
      synaptogenesis and the expression of specific cell markers, such as the S-100
      protein and olfactory marker protein (OMP). Positive immunohistochemical staining
      for N-cadherin in human fetuses suggests that growth of olfactory axons to their
      target may be mediated by cell adhesion molecules. The overall data presented
      here indicate that this pathway develops more precociously in humans than in
      rodents. Whether this translates also to earlier functional maturity remains to
      be elucidated.

PMID- 1392074
TI  - Fine structure of the vomeronasal and septal olfactory epithelia and of glandular
      structures.
AB  - The vomeronasal and septal olfactory organs are two neurosensory structures in
      the mammalian nasal septum which are poorly understood relative to the main
      olfactory system. The vomeronasal organ is a paired, blind-ending tubular
      structure that opens rostrally into the nasal cavity in some species and into the
      incisive ducts in others. When present in mammals, the septal olfactory organ is
      an island of olfactory mucosa positioned such that it is in the primary air
      pathway in the caudal portion of the nasal cavity. Mammalian nasal glands, with a
      diverse histochemical and ultrastructural morphology, secrete a variety of
      substances onto the mucosal surface. One of these substances, odorant binding
      protein, localized in bovine nasal glands and lateral nasal glands of rodents,
      may be important in the capture and conveyance of odorant molecules to olfactory
      receptors. The objectives of this paper are to present original data while
      reviewing the literature on the ultrastructure of vomeronasal and septal
      olfactory neuroepithelia, and of vomeronasal, bovine nasal, and lateral nasal
      glands. Nasal tissues from pigs, calves, and hamsters were prepared for electron
      microscopy. Neurosensory epithelia of the porcine vomeronasal organ and the
      hamster septal olfactory organ are similar to that described for the vomeronasal
      and septal olfactory organs of other mammals. Bovine nasal and rodent lateral
      nasal glands consist of subregions which differ morphologically; the most
      abundant acinar cell type in the bovine nasal gland contains lightly electron
      dense secretory granules while that of the rodent lateral nasal gland contains
      both small electron dense and large, electron lucent granules. The porcine
      vomeronasal gland contains numerous small, dense granules of a diverse
      morphology.

PMID- 1392075
TI  - Use of ferrofluids to obtain magnetic domain images in AFM.

PMID- 1392076
TI  - Microcirculatory profile in myocutaneous island flaps. An experimental study in
      pigs.

PMID- 1392077
TI  - Bringing the basic scientist into human disease research.

PMID- 1392079
TI  - A developmentally regulated Caulobacter flagellar promoter is activated by 3'
      enhancer and IHF binding elements.
AB  - The transcription of a group of flagellar genes is temporally and spatially
      regulated during the Caulobacter crescentus cell cycle. These genes all share the
      same 5' cis-regulatory elements: a sigma 54 promoter, a binding site for
      integration host factor (IHF), and an enhancer sequence, known as the ftr
      element. We have partially purified the ftr-binding proteins, and we show that
      they require the same enhancer sequences for binding as are required for
      transcriptional activation. We have also partially purified the Caulobacter
      homolog of IHF and demonstrate that it can facilitate in vitro integrase-mediated
      lambda recombination. Using site-directed mutagenesis, we provide the first
      demonstration that natural enhancer sequences and IHF binding elements that
      reside 3' to the sigma 54 promoter of a bacterial gene, flaNQ, are required for
      transcription of the operon, in vivo. The IHF protein and the ftr-binding protein
      is primarily restricted to the predivisional cell, the cell type in which these
      promoters are transcribed. flaNQ promoter expression is localized to the swarmer
      pole of the predivisional cell, as are other flagellar promoters that possess
      these regulatory sequences 5' to the start site. The requirement for an IHF
      binding site and an ftr-enhancer element in spatially transcribed flagellar
      promoters indicates that a common mechanism may be responsible for both temporal
      and polar transcription.

PMID- 1392082
TI  - The American Society for Cell Biology 32nd annual meeting. November 15-19, 1992,
      Denver, Colorado. Abstracts.

PMID- 1392078
TI  - A mutant nuclear protein with similarity to RNA binding proteins interferes with
      nuclear import in yeast.
AB  - We have isolated mutants of the yeast Saccharomyces cerevisiae that are defective
      in localization of nuclear proteins. Chimeric proteins containing the nuclear
      localization sequence from SV40 large T-antigen fused to the N-terminus of the
      mitochondrial F1 beta-ATPase are localized to the nucleus. Npl (nuclear protein
      localization) mutants were isolated by their ability to grow on glycerol as a
      consequence of no longer exclusively targeting SV40-F1 beta-ATPase to the
      nucleus. All mutants with defects in localization of nucleolar proteins and
      histones are temperature sensitive for growth at 36 degrees C. Seven alleles of
      NPL3 and single alleles of several additional genes were isolated. NPL3 mutants
      were studied in detail. NPL3 encodes a nuclear protein with an RNA recognition
      motif and similarities to a family of proteins involved in RNA metabolism. Our
      genetic analysis indicates that NPL3 is essential for normal cell growth; cells
      lacking NPL3 are temperature sensitive for growth but do not exhibit a defect in
      localization of nuclear proteins. Taken together, these results indicate that the
      mutant forms of Npl3 protein isolated by this procedure are interfering with
      nuclear protein uptake in a general manner.

PMID- 1392080
TI  - Periodic changes in phosphorylation of the Xenopus cdc25 phosphatase regulate its
      activity.
AB  - The cdc25 tyrosine phosphatase is known to activate cdc2 kinase in the G2/M
      transition by dephosphorylation of tyrosine 15. To determine how entry into M
      phase in eukaryotic cells is controlled, we have investigated the regulation of
      the cdc25 protein in Xenopus eggs and oocytes. Two closely related Xenopus cdc25
      genes have been cloned and sequenced and specific antibodies generated. The cdc25
      phosphatase activity oscillates in both meiotic and mitotic cell cycles, being
      low in interphase and high in M-phase. Increased activity of cdc25 at M-phase is
      accompanied by increased phosphorylation that retards electrophoretic mobility in
      gels from 76 to 92 kDa. Treatment of cdc25 with either phosphatase 1 or
      phosphatase 2A removes phosphate from cdc25, reverses the mobility shift, and
      decreases its ability to activate cdc2 kinase. Furthermore, the addition of
      okadaic acid to egg extracts arrested in S-phase by aphidicolin causes
      phosphorylation and activation of the cdc25 protein before cyclin B/cdc2 kinase
      activation. These results demonstrate that the activity of the cdc25 phosphatase
      at the G2/M transition is directly regulated through changes in its
      phosphorylation state.

PMID- 1392083
TI  - Let not thy left hand know.

PMID- 1392084
TI  - The Brown University School of Medicine Class of 1992.

PMID- 1392081
TI  - Regulation of gene expression in PC12 cells via an activator of dual second
      messengers: pituitary adenylate cyclase activating polypeptide.
AB  - In this study we demonstrate that the activator protein-1 (AP-1) DNA motif,
      initially considered to be unresponsive to cyclic AMP (cAMP), does function as a
      cAMP-response element in PC12 cells. A luciferase reporter gene driven by the
      collagenase promoter that contains the AP-1 motif is responsive to cAMP as well
      as phorbol esters when transfected in PC12 cells. We have recently shown that
      pituitary adenylate cyclase activating peptide (PACAP) has neurotrophic
      properties and activates both adenylylcyclase and the inositol lipid cascade in
      PC12 cells. Consistent with these actions, we demonstrate that PACAP is an
      effective activator of luciferase reporter genes whose promoters bear the AP-1
      motif, as well as the related DNA element that binds the protein CREB. Both the
      cAMP and inositol lipid pathways appear to play a role in the activation of these
      motifs by PACAP. Mutation of the AP-1 motif and its juxtaposition to a
      heterologous promoter proves that the AP-1 motif is a locus for response to cAMP
      and PACAP. The luciferase reporter genes bearing the AP-1 motif are not cAMP
      responsive in HeLa tk- cells, indicating that the mode of second-messenger
      responsiveness is cell-type specific.

PMID- 1392085
TI  - A statistical profile of the practicing physicians of Rhode Island.

PMID- 1392086
TI  - Women in medicine in the 1990s.

PMID- 1392087
TI  - Hospitalizations with head and spinal cord injuries.

PMID- 1392088
TI  - Percutaneous abdominal biopsy.
AB  - The radiologically guided percutaneous needle biopsy is of proven value for
      evaluating intra-abdominal disease. Every region of the abdomen and pelvis is
      amenable to fine-needle biopsy. Accuracy rates are high with minimal risk to the
      patient. Current trends in biopsies tend to favour the use of larger core biopsy
      needles (18-gauge Biopty), and preliminary reports suggest that this is safe and
      may increase the diagnostic accuracy. Clinicians need not hesitate to call on
      their radiological colleagues to perform this most important procedure.

PMID- 1392089
TI  - Transjugular and plugged liver biopsies.
AB  - When a liver biopsy is indicated the transabdominal approach using either a
      Menghini or Tru-Cut needle has been shown to be an extremely safe procedure with
      very low morbidity and mortality rates in patients with normal or only mildly
      disturbed coagulation. When the coagulation status is severely deranged, however,
      several methods of obtaining a liver biopsy have been devised to circumvent the
      increased risk of bleeding. The transjugular approach has been shown to be both
      successful and relatively safe. The less cumbersome technique of plugging the
      needle track after percutaneous transabdominal biopsy has been reported
      relatively recently. Although it is likely that the latter method will produce
      good biopsy samples in the majority of cases (and in this regard it may prove to
      be better than the transjugular route), considerably more experience is required
      before its true complication rate is known. In a hospital where large numbers of
      transjugular biopsies are performed by experienced radiologists and in which
      skilled pathologists are used to interpreting the histological appearances of
      small, crushed liver samples, there is no compelling reason to change to the
      plugged biopsy technique. The more difficult question is whether hospitals in
      which the radiological and histological skills necessary for consistent success
      with the transjugular approach are not available should adopt the plugged biopsy
      method. The answer to this question is probably in the affirmative, but will
      depend on the confidence and interventional experience of the local operator and
      on more detailed factual information concerning the safety of the plugged method.
      With regard to the latter point, the publication of a large controlled study on
      the safety and efficacy of plugged liver biopsy would be a valuable contribution
      to the world literature on the subject.

PMID- 1392090
TI  - Percutaneous management of pancreatic fluid collections.
AB  - Percutaneous catheter drainage of both infected and non-infected pancreatic fluid
      collections is a safe, efficacious procedure. The results of this procedure
      depend upon proper selection of patients based upon their clinical status as well
      as the morphological findings depicted by computed tomography and endoscopic
      retrograde cholangiopancreatography, careful preprocedural planning and execution
      of the drainage procedure, good catheter care with follow-up imaging and contrast
      studies, and attention to the criteria of catheter removal. An average success
      rate of 80% should be expected with a complication rate of about 15%.

PMID- 1392091
TI  - Percutaneous management of intraperitoneal, hepatic and other fluid collections.

PMID- 1392093
TI  - The radiological management of gastrointestinal strictures and other obstructive
      lesions.
AB  - Balloon dilation of gastrointestinal strictures using a radiologic, endoscopic or
      combined approach is a safe, effective means of managing an ever-increasing
      variety of stricturing processes. At present the ability to dilate strictures in
      the gastrointestinal tract is limited mainly by access. Balloon dilation is now
      well established in the management of oesophageal and anastomotic lesions. The
      place of balloon dilation in the management of Crohn's disease and in the
      management of malignant disease requires further evaluation.

PMID- 1392092
TI  - Percutaneous radiologic gastrostomy.
AB  - Percutaneous radiologic gastrostomy is comparable to endoscopic gastrotomy in its
      simplicity, high success rate and lack of complications. Furthermore, it compares
      favourably with endoscopic gastrostomy in significant aspects such as a lower
      incidence of wound infection, reduced risk of aspiration and ease of conversion
      to jejunal placement. There are also fewer contraindications to radiologic
      placement and the cost is likely to be less than for endoscopic gastrostomy.
      Since the emergence of percutaneous endoscopic gastrostomy, clinicians have been
      re-evaluating the role of the gastrostomy in managing patients requiring
      nutritional support or gastrointestinal decompression. Percutaneous radiologic
      gastrostomy is an eminently suitable alternative to endoscopic or surgical
      gastrostomy.

PMID- 1392094
TI  - The management of problematic biliary calculi.
AB  - Recent advances in modern medical technology have significantly reduced the
      number of patients with 'problematic calculi'. When a patient does present with a
      difficult bile duct stone, various non-surgical treatment options are now
      available. In experienced hands, with healthy or high-risk patients, percutaneous
      treatment is as safe and as efficacious as endoscopy or surgery. Since it does
      not require general anaesthesia, and patients recover much more quickly than
      after surgery, the percutaneous approach is preferred when endoscopy fails to
      achieve ductal clearance. Surgery is indicated for patients with lesions
      requiring surgical removal or correction, but seldom for removal of biliary
      calculi alone.

PMID- 1392096
TI  - Transjugular intrahepatic portosystemic stent shunt.

PMID- 1392095
TI  - Interventional radiology of the gallbladder.

PMID- 1392097
TI  - Immune responses following competitive water tests in two species of macaques.
AB  - A panel of immune parameters (lymphocyte activation by mitogens, natural
      cytotoxicity, and differential cell counts) was assessed in socially housed
      pigtail and bonnet macaques 1 and 2 weeks before, 48 h after, and 1 and 2 weeks
      after a competitive water test. Species differences were found in both baseline
      measures and the responses to the test: Immune measures observed during baseline
      periods were lower in pigtail macaques. Furthermore, only the pigtail macaques
      showed changes in mitogen activation and cytotoxicity at 48 h post-test.
      Dominance-related behaviors affected these responses both within and across
      social groups. The species differences may be accounted for by the differences in
      the behavioral responses of the two species to the test: Pigtail macaques
      consistently contested access to the water during the test, whereas bonnet
      macaques did not. These results suggest that the immune system can be modulated
      by psychosocial behavioral systems, particularly during times of stress.

PMID- 1392098
TI  - Action of interleukin-2 and interleukin-4 on CRF mRNA in the hypothalamus and
      POMC mRNA in the anterior pituitary.
AB  - We have used the technique of in situ hybridization histochemistry to determine
      corticotropin-releasing factor (CRF) mRNA in the hypothalamic paraventricular
      nucleus (PVN) and proopiomelanocortin (POMC) mRNA in the anterior pituitary of
      rats given a single ip injection of either interleukin (IL)-2 or IL-4. IL-2
      increased POMC mRNA in the anterior pituitary in a dose-dependent manner. The
      effect was apparent both at 4 and 24 h after injection. No effect of IL-2 on CRF
      mRNA in the PVN was detected in these animals, suggesting that the increase in
      POMC mRNA was not driven by an increase in CRF. IL-4 was without effect at the
      hypothalamic level although this cytokine did result in a decrease in POMC mRNA
      in the anterior pituitary.

PMID- 1392099
TI  - The neural and neuro-endocrine component of the human thymus. I. Nerve-like
      structures.
AB  - The presence of nerve-like fibers in the human thymus was studied by
      immunohistochemistry on frozen tissue sections and sections of formalin-fixed
      paraffin-embedded tissue, for neurofilaments (Nf) of 68-, 160-, and 200-kDa
      (neuron-specific structural proteins), neuron-specific protein PGP9.5, tyrosin
      hydroxylase (noradrenergic innervation), chromogranin A (CHROM), synaptophysin
      (SYN), and the pituitary hormones follicle-stimulating hormone (FSH) and its beta
      subunit, growth hormone, adrenocorticotropic hormone, luteinizing hormone,
      prolactin, beta-subunit of thyroid-stimulating hormone, and somatostatin.
      Noradrenergic profile-like immunoreactivity was observed in the medulla:
      immunolabeling was observed also for epithelial cells surrounding Hassall's
      corpuscles. For neurofilaments, only Nf 160-kDa immunoreactivity was observed in
      the thymic parenchyma, mainly in long-sized labeling patterns in the medulla.
      PGP9.5 immunolabeling occurred especially in the cortex, in dendritic labeling
      patterns compatible with the epithelial network at this location. The medulla
      showed PGP9.5 immunoreactivity in fiber-like patterns and in large-sized
      epithelial cells surrounding Hassall's corpuscles. Immunoreactive CHROM was seen
      in profile-like structures in the subcapsule, cortex, and medulla. SYN
      immunolabeling occurred focally around Hassall's corpuscles. Profile-like
      structures immunoreactive for pituitary hormones were observed in the medulla and
      in less density in the cortex. For FSH the highest density occurred in the
      cortex, where long-sized profile-like structures were present running over and in
      between cells, especially in the keratin-positive epithelial dendritic network
      (two-color immunohistochemistry).

PMID- 1392100
TI  - The neural and neuro-endocrine component of the human thymus. II. Hormone
      immunoreactivity.
AB  - We evaluated the presence of anterior pituitary hormones; follicle-stimulating
      hormone (FSH) and its beta-subunit (beta-FSH), luteinizing hormone (LH) and its
      beta-subunit (beta-LH), beta-subunit of thyroid-stimulating hormone (beta-TSH),
      adrenocorticotropic hormone (ACTH), growth hormone (GH), and prolactin (PRL); the
      placental hormone human chorionic gonadotropin (hCG); and somatostatin, in
      paraffin and frozen sections of the human thymus. Epithelial cells in the medulla
      were immunoreactive for most of these hormones, in varying density and intensity
      of labeling. The cells labeled varied from epithelial cells surrounding Hassall's
      corpuscles toward solitary cells or small epithelial aggregates in the medulla.
      FSH immunoreactivity did occur predominantly in epithelial cells of the cortex,
      in apparent contrast to the predominant medullary location of cells immunolabeled
      for beta-FSH. The epithelial nature of FSH-immunoreactive cells was confirmed by
      two-color immunohistochemistry with anti-keratin antibody. In addition to FSH,
      some epithelial cells in subcapsule and cortex were labeled by antibodies to beta
      FSH, beta-LH, beta-TSH, ACTH, GH, and PRL. Some macrophage-like cells surrounded
      by a rosette of lymphocytes were immunoreactive for FSH and GH. Some
      interdigitating reticulum-like cells were labeled by anti-beta-LH. Immunolabeling
      of lymphocytes was found for hCG, especially lymphocytes in the medulla. Two
      color immunohistochemistry with anti-CD3 revealed a strong CD3 expression on hCG
      immunoreactive cells, whereas CD3-negative cells were hCG-negative. T cells
      immunolabeled for hCG were also found in peripheral lymphoid organs.

PMID- 1392101
TI  - A behavioral profile of autoimmune lupus-prone MRL mice.
AB  - Manifestations of the human autoimmune disease systemic lupus erythematosus (SLE)
      include a number of behavioral and cognitive deficits. The present study asks
      whether neurobehavioral dysfunction is present also in MRL mice that
      spontaneously develop most of the fundamental immunological aberrations of SLE.
      There are two congenic substrains of MRL mice that differ in the time of disease
      onset: MRL-lpr mice develop lupus early and MRL(-)+/+ develop the typical signs
      of disease relatively late in life. The behavior of these substrains was assessed
      at 7 to 11 weeks of age, a time that coincides with the onset of disease in MRL
      lpr mice and the absence of known lupus symptoms in the MRL(-)+/+ group. When
      compared to the congenic MRL(-)+/+ control substrain, MRL-lpr mice were
      spontaneously less active, traversed a crossbeam slower, and ceased responding to
      the novelty of a new environment sooner. They were also more reluctant to leave
      their home base or travel far away from it and perseverated in their response
      bias during extinction and reversal learning. Immunological status was
      characterized by moderate proteinuria in both substrains and high titers of
      antinuclear antibodies in MRL-lpr but not MRL(-)+/+ mice. Histological analysis
      revealed minimal or no signs of joint pathology in MRL-lpr mice. Thus, this study
      shows the presence of behavioral dysfunction in mice with early stages of
      autoimmune disease and gives support for the idea that MRL mice may provide a
      useful model of neurobehavioral dysfunction in SLE. It is suggested that the
      behavioral profile of MRL-lpr mice may indicate increased "timidity," related to
      genetics, autoimmunity, or both.

PMID- 1392102
TI  - Serum autoantibodies against glial fibrillary acidic protein in brain aging and
      senile dementias.
AB  - Autoantibodies against glial fibrillary acidic protein (GFAP) were investigated
      by ELISA test in sera of patients suffering from senile dementias and in healthy
      aging people. One hundred eight subjects divided into control, vascular dementia
      (VD), presenile Alzheimer's disease (AD), and senile Alzheimer's disease (SDAT)
      groups were included in the study. VD patients showed the highest antibody titers
      when compared to controls, whereas AD had the lowest titers when compared to the
      other groups. These results do not support the utility of anti-GFAP antibodies as
      useful markers of Alzheimer's disease, suggesting that their presence is a
      secondary phenomenon to blood-brain barrier disruption.

PMID- 1392103
TI  - Corticosterone-independent alteration of lymphocyte mitogenic function by
      amphetamine.
AB  - Amphetamine, a neural stimulatory agent with acute effects mimicking those of
      stress, is shown here to elevate plasma corticosterone levels and suppress spleen
      and peripheral blood lymphocyte (PBL) mitogenic responses to concanavalin A (Con
      A) and phytohemagglutinin (PHA) when administered to rats. Pretreatment of the
      rats with propranolol, a nonselective beta-adrenergic receptor antagonist,
      totally prevented the amphetamine-induced suppression of lymphocyte mitogenic
      reactivity to Con A and PHA in the spleen and to PHA in the peripheral blood;
      however, the PBL mitogenic response to Con A was only partially restored.
      Although the amphetamine-induced alterations in immune function were prevented by
      propranolol pretreatment, the elevated plasma corticosterone response was not.
      This suggests that corticosterone is not modulating the mitogenic activity of
      splenic lymphocytes or PHA-reactive PBLs. On the other hand, Con A-reactive PBLs
      may be affected by corticosterone and/or other mechanisms, which may include the
      catecholamines.

PMID- 1392104
TI  - A thymocytotoxic autoantibody reacts with the mouse brain cells in culture.
AB  - Autoimmune-prone New Zealand Black mice produce a large amount of autoantibodies
      cytotoxic for thymocytes (natural thymocytotoxic autoantibodies, NTA). A
      monoclonal NTA (NTA260) has been found to react with brain tissues as well as the
      cell surface of thymocytes. We investigated the expression of NTA 260 antigen in
      the primary culture of fetal brain cells. NTA260 labeled strongly the cytoplasm
      of nerve cells after fixation, but failed to stain the living cells. Western blot
      analysis revealed that NTA260 recognized predominantly a band at approximately 53
      kDa in brain and thymic extracts. These findings indicate that neuronal NTA260
      antigen, which has a molecular mass similar to that of thymocytes, is likely an
      intracellular component.

PMID- 1392105
TI  - Lack of [3H]quinuclidinyl benzylate binding to biologically relevant binding
      sites on mononuclear cells.
AB  - We analyzed the binding characteristics of [3H]quinuclidinyl benzylate ([3H]QNB),
      a muscarinic cholinergic ligand, to rat and human mononuclear cells (MNC). Under
      various assay conditions, atropine-sensitive, saturable binding occurred with an
      apparent Kd of 10 nM. Conditions which disrupted the MNC membrane reduced total
      binding and eliminated specific binding. Muscarinic agonists were unable to
      inhibit [3H]QNB binding to MNC at concentrations up to 10(-2) M. Stereoisomers
      dexetimide and levetimide were equipotent inhibitors of binding (IC50 2 x 10(-5)
      M). We conclude that, although atropine-sensitive binding of [3H]QNB to MNC
      occurs, the binding is not consistent with the presence of a biologically
      relevant muscarinic cholinergic receptor.

PMID- 1392106
TI  - Retinoids and contraception.
AB  - The main side effect of the retinoids is teratogenicity. Every dermatologist has
      a moral obligation to ensure that this effect is avoided, and the present
      publication is aimed at helping prescribe these drugs. After a review of the key
      properties of each of the retinoids on the market, the different forms of
      contraception available and their indication in young patients undergoing
      retinoid treatment are discussed. Unless otherwise contraindicated, oral
      contraception with an estrogen-progestogen formulation is the contraceptive
      method of choice for women undergoing retinoid treatment. The intrauterine device
      (IUD) is of little or almost no relevance for young women undergoing treatment
      with a retinoid. IUDs are indicated in older multiparae who have practised this
      form of contraception before starting retinoid treatment and who refuse to take
      the pill. Natural and local methods of contraception are totally unsuitable for
      women undergoing treatment with retinoids. However, they may be used as an
      additional precautionary measure by IUD users.

PMID- 1392107
TI  - Serum SC5b-9 (terminal complement complex) level, a sensitive indicator of
      disease activity in patients with Henoch-Schonlein purpura.
AB  - The concentration of the terminal complement complex (TCC), SC5b-9, was
      determined by enzyme immunoassay using 95 serum samples from 30 patients with
      Henoch-Schonlein purpura (HSP), 27 with other forms of inflammatory skin disease
      and 20 normal healthy donors. Twenty-five patients with HSP showed significantly
      increased TCC concentration in the active phase of the disease, during which
      newly formed urticarial or purpuric macules/papules could be seen. Skin biopsy
      specimens of skin lesions from patients with elevated TCC levels in nearly all
      cases contained the membrane attack complex of complement and consisted of C5b,
      C6, C7, C8, C9 without S protein on the vessel walls. Systemic and local
      activation of complement may thus possibly occur in HSP. Three patients with
      various manifestations of the disease were followed over a period of several
      years during which the active and inactive phases were scanned. TCC elevation in
      all cases was correlated with exacerbation of the disease. In contrast, C3, C4
      and CH50 levels either remained normal or increased and thus were not reliable
      indicators of disease activity. Measurement of TCC should thus prove quite useful
      for monitoring the activity of HSP in patients in whom there is complement
      activation and also serve to facilitate clarification of the functions of
      complement in the pathogenesis of the disease.

PMID- 1392108
TI  - Xeroderma pigmentosum variant associated with multiple skin cancers and a lung
      cancer.
AB  - A 65-year-old Japanese man with a xeroderma pigmentosum (XP) variant, XP127TO, is
      described. The XP127TO skin fibroblasts exhibited the typical XP variant
      characteristics of a 1.5-fold higher sensitivity than normal cells to the lethal
      effect of 254 nm ultraviolet (UV) light and the normal level of unscheduled DNA
      synthesis induced by 254 nm UV. Caffeine dose-dependently increased the cytotoxic
      effect of 254 nm UV on XP127TO cells. Clinically, the patient developed not only
      3 cutaneous squamous cell carcinomas on sun-exposed areas but also an
      adenocarcinoma of the upper lobe of the right lung. A review of the 14 documented
      Japanese XP patients with nonskin malignancies indicates that the incidence of
      nonskin malignancy in XP patients is much lower than that of skin cancer in XP
      but higher than that in the general population.

PMID- 1392109
TI  - Soluble interleukin-2 receptor, CD4 and CD8 levels in melanoma: a longitudinal
      study.
AB  - Serum levels of soluble(s) interleukin-2 receptor (IL-2R), sCD4 and SCD8 were
      analysed in 227 melanoma patients, using a sandwich enzyme immunoassay. Different
      stages of the disease were considered, and a longitudinal study with a 2-year
      follow-up was performed. Mean values of sIL-2R were significantly higher than in
      normal controls in all stages and correlated with the disease progression. sCD8
      increases with stage progression were less striking, while sCD4 values were
      always in the normal range. We conclude that sIL-2R measurement is a useful
      clinical parameter in monitoring disease evolution in melanoma.

PMID- 1392110
TI  - Practical considerations of melanoma/skin cancer screening clinics.
AB  - In 1989 a voluntary melanoma/skin cancer screening clinic was held in Oss, the
      Netherlands. The campaign was carried out according to the free clinics conducted
      since 1985 in the USA. Our experiences with the first clinic urged us to improve
      on the organization of the screen. This produced a better yield of the second
      screen, conducted in 1990 in Arnhem. In this paper we present the practical and
      organizational implications of melanoma/skin cancer screening based on both
      screening exercises. It is emphasized that only dermatologists should screen.
      Concomitant public education will enhance self-selection of people at risk for
      melanoma/skin cancer. There should be ample provider time, sufficient auxiliary
      personnel and abundant examination rooms. Total-body skin examination is
      optional. Follow-up of positive screenees is mandatory. It is concluded that
      melanoma/skin cancer screening is feasible, particularly in countries with a high
      dermatologist-to-patient ratio.

PMID- 1392111
TI  - Use of topical lithium succinate in the treatment of seborrhoeic dermatitis.
AB  - Twenty-one patients with seborrhoeic dermatitis were included in an open trial of
      lithium succinate ointment (LSO) for a total duration of 8 weeks. The same
      clinician made assessments of the severity of redness, scaling, greasiness and
      overall clinical impression of the condition every 2 weeks. Because the results
      appeared to be satisfactory, we decided to perform a double-blind, placebo
      controlled trial of LSO. Thirty patients with seborrhoeic dermatitis were
      included. The results also demonstrated the beneficial effect of LSO. A
      significantly higher number of patients treated with LSO showed remission or
      marked improvement compared with placebo. The main adverse events demonstrated
      consisted of minor transient skin irritation and/or stinging sensation. Studying
      the in vivo inhibitory effect of LSO on the growth of Pityrosporum revealed that
      Pityrosporum did not significantly have its growth inhibited by lithium. Topical
      lithium succinate appears to be a safe and an effective treatment for seborrhoeic
      dermatitis. The product presumably acts as an anti-inflammatory agent.

PMID- 1392112
TI  - Topical immunotherapy for alopecia areata: re-evaluation of 139 cases after an
      additional follow-up period of 19 months.
AB  - Within a group of 139 patients previously studied during treatment for alopecia
      areata with diphenylcyclopropenone (DCP), hair growth was re-evaluated after a
      period of 19 months following completion of our previous study. Fifty-four
      patients treated with DCP had total and 6 had partial but cosmetically acceptable
      regrowth. Twenty-five patients with total regrowth had stopped DCP treatment for
      a mean period of 15 months and had not relapsed. Nineteen of 28 patients who
      still applied DCP were in the process of stepwise discontinuation of treatment.
      Fifteen patients had subsequently been treated with squaric acid dibutylester
      (SADBE) after having acquired 'tolerance' to DCP; at the time of re-evaluation 3
      of these patients had complete regrowth, and 4 patients had partial but
      cosmetically acceptable regrowth. Topical immunotherapy with DCP and SADBE had
      resulted in total regrowth in 57/139 patients (41.0%) and in partial but
      cosmetically satisfactory regrowth in 10/139 patients (7.2%). The type of
      involvement and duration of alopecia areata were factors of prognostic
      significance.

PMID- 1392114
TI  - Three cases of allergic dermatitis due to intravesical mitomycin C.
AB  - Irritant contact dermatitis has frequently been described in association with
      mitomycin instillation into the bladder. Three cases of allergic contact
      dermatitis in which patch tests demonstrated a type IV hypersensitivity reaction
      are reported. Patients showing skin reaction during mitomycin C vesical
      instillation should be patch tested to make a decision whether the drug might be
      continued (toxic reaction) or discontinued (allergic reaction).

PMID- 1392113
TI  - Cyclic neutropenia: a cause of recurrent aphthous stomatitis not to be missed.
AB  - Cyclic neutropenia is a rare hematological disorder consisting of recurrent
      episodes of aphthous stomatitis and skin infections caused by a periodic decrease
      in blood neutrophil counts. We present the case of such a patient successfully
      treated with steroids. Recurrent aphthous stomatitis with a periodicity of around
      3 weeks should alert the dermatologist to the possibility of cyclic neutropenia.

PMID- 1392115
TI  - Phthalic acid dermatitis caused by an organostannic compound, tributyl tin
      phthalate.
AB  - We report a case of primary irritant contact dermatitis caused by an
      organostannic insecticide, tributyl tin phthalate, which has been thought to be
      stable and safe. A factory worker has been in contact with raw tributyl tin
      phthalate on one leg. Soon after taking a hot-water bath, he developed severely
      painful erythema on this leg. Patch tests and chemical analysis revealed that hot
      water hydrolyzed tributyl tin phthalate and produced concentrated phthalic acid.
      Since phthalic acid, a weak acid, was then concentrated, an acute irritant
      reaction appeared in this patient.

PMID- 1392116
TI  - Squamous cell carcinoma--70 years after irradiation.
AB  - The rare event of invasive squamous cell carcinoma 70 years after irradiation to
      the scalp for tinea capitis, occurred in a 75-year-old Caucasian male. The
      clinical, histological, roentgenologic and magnetic resonance imaging picture are
      described, and the literature is reviewed.

PMID- 1392117
TI  - Doubled nail of the thumb. A rare form of polydactyly.
AB  - Bifid thumb is a rare manifestation of polydactyly. The trait is autosomal
      dominant, but the expressivity is highly variable. It must be distinguished from
      apical dystrophy, a rare form of brachydactyly. Severe surgical procedures have
      been suggested for both functional and cosmetic reasons. Two families affected
      are described.

PMID- 1392118
TI  - Eccrine angiomatous hamartoma: a multiple variant.
AB  - A case of multiple eccrine angiomatous hamartoma present in a boy since birth is
      reported. Clinically, this condition must be differentiated from other neonatal
      angiomatoses. Sometimes the clinical findings are nonspecific, whereas histologic
      examination may exclude angiomatoses with visceral involvement. In our case the
      hamartomatous nature of this tumor is documented also by the presence of pilar
      structures intimately related to the eccrine-angiomatous complex in one of two
      lesions histologically examined. Therefore, the histologic classification of
      eccrine angiomatous hamartoma into subgroups seems to be excessive.

PMID- 1392119
TI  - Dysplastic nevus syndrome: intrafamilial identification of carriers by
      cytogenetics.
AB  - Seven members of a family with dysplastic nevus syndrome (DNS) were examined
      clinically; skin biopsies of unaffected skin from 6 were taken. Biopsy-derived
      cultivated fibroblasts were examined by cytogenetic methods, i.e. by measuring
      the spontaneous and the UVB- and UVC-driven increase in sister chromatid exchange
      (SCE). A male patient with malignant melanoma, his son and his nephew, both with
      multiple dysplastic nevi, showed a distinctive elevation of UV-induced SCE,
      whereas the other, unaffected members of the family showed normal values. These
      results give evidence that in siblings with DNS the affected members can be
      identified not only on clinicopathological grounds but also by UV-induced
      elevated SCE at the cytogenetic level.

PMID- 1392120
TI  - Antibiotic therapy in a boy affected by generalized epidermolytic hyperkeratosis.

PMID- 1392121
TI  - Generalized epidermolysis bullosa with congenital synechiae-associated
      malformations and unusual ultrastructure: a new entity?

PMID- 1392122
TI  - Lichen planus and virus C hepatitis: disappearance of the lichen under interferon
      alfa therapy.

PMID- 1392124
TI  - Leucotrichia in discoid lupus erythematosus.

PMID- 1392123
TI  - Pemphigus and intraepidermal IgA.

PMID- 1392125
TI  - Serum levels of soluble interleukin-2 receptor in systemic and circumscribed
      scleroderma.

PMID- 1392126
TI  - In memory of Arthur Rook.

PMID- 1392127
TI  - [Effects of tiropramide on the activity of lower urinary tract in dogs and its
      interpretation].
AB  - The rhythmic contractions of urinary bladder under constant volume condition were
      evoked in decerebrate and de-anesthetized dogs, while various myogenic and nerve
      mediated electrical and mechanical activities of smooth muscles were recorded
      from in vivo pelvic viscera. The vesical rhythmic contractions were transiently
      and partially blocked by intravenous application of tiropromide. This 'partial'
      block showed a good contrast to the 'complete' block of identical contractions,
      which was observed after application of oxybutynin, known as a potent anti
      muscarinic drug. The bladder voiding cycles were observed in other decerebrate
      dogs, while the warmed Ringer solution was infused at a steady rate into the dome
      of the bladder until principal voiding contraction occurred in cystometric
      recordings. The initiation of voiding contraction was markedly delayed after
      intravenous injection of tiropramide. The delay of principal contraction was
      found to be due to successive appearance of falling waves in cystometric
      recordings. As a evident contrast, terodiline caused a significant reduction of
      voiding contraction height and shortening of clonic discharge phase of external
      urethral sphincters during voiding cycle. It is concluded that tiropramide does
      not reveal anti-muscarinic action which oxybutynin or terodiline does really
      show, instead tiropramide acts principally on bladder detrusor itself, especially
      on its relaxation phase of premature contraction to be prolonged. The evidences
      were also presented for electrophysiological identification of bladder detrusor
      and urethral smooth muscle.

PMID- 1392128
TI  - [An experimental study of the diurnal changes in colonic motility centering on
      defecation].
AB  - The following findings have been obtained as a result of making an assessment
      regarding the diurnal changes in colonic motility by means of continuous
      measurement of contractile waves by using strain gauge force transducers and
      roentgenographic observation in conscious dogs. 1. Before defecation, the
      contractile force of the wave was weak, frequency of its emergence was also
      small, and transfer of intestinal content was slow, showing decrease of colonic
      motility. 2. After defecation, the gradually increasing and decreasing
      contractile wave groups became clear, and the contractile force was intensified
      concurrently with increase of its emerging frequency. Transfer of intestinal
      content to the anal side was rapid, and recovery of colonic motility was
      observed. 3. The recovery of the colonic motility after defecation was observed
      regardless of digestive or interdigestive state. 4. By intake of food, increase
      of the colonic motility corresponding to gastrocolic response was observed, but
      it was due to the increase of emerging frequency of contractile wave, for which
      no change was observed in contractile force or duration in each individual waves.
      5. It was suggested that the contractile motion which undergoes gradual increase
      and decrease is the basic pattern in the colonic motility and that the colonic
      motility changes by the differences of amount, shape and hardness of intestinal
      content, and decreases gradually along with increase of intestinal content, but
      the basic pattern of contractile motion is restored by inflow of intestinal
      content into the colon which became empty after defecation. From the above it was
      considered to be inadequate to use the pattern classification of digestive and
      interdigestive state for the analysis of colonic motility and that assessments
      should be made centering on defecation.

PMID- 1392129
TI  - Vaso-contractile responsiveness of perfused arterial segments to platelet-derived
      thromboxane A2.
AB  - It remains not entirely accepted that changes in prostanoid metabolism in the
      blood vessel wall, as well as in whole blood, have a certain influence on
      vascular responsiveness to vasoactive agents. The aim of the present study is to
      elucidate whether platelet-derived thromboxane A2 (TxA2) participates in
      enhancement of vasoconstractile response to a pressor agent. Platelet aggregation
      was extraluminally induced by application of collagen to autologous platelet rich
      plasma (PRP), and then the PRP treated with collagen was infused into the
      perfusion system by means of a small infusion pump. All the prostanoids in the
      perfusate were assayed radioimmunologically. Infusion into the perfusion system
      of PRP treated with collagen, as well as that of untreated PRP, apparently caused
      pronounced enhancement of vasocontractile response to noradrenaline (NA),
      accompanied by elevations of both the level of TxB2, a stable metabolite of TxA2,
      and the TxB2/prostaglandin E (PGE) ratio. In addition, treatment with either OKY
      046 (a Tx A2 synthetase inhibitor) or ketanserin (a selective S2-serotonergic
      antagonist) resulted in diminution of the raised vasoconstrictor response to NA
      induced by application of collagen to PRP. Thus, it is possible to draw the
      conclusion that platelet-derived TxA2, is as potent a vasoactive substance as 5
      hydroxytryptamine (5-HT) and at least in part, contributes to the enhancement of
      vasocontractile response to NA (NA-R) during raised platelet aggregability.

PMID- 1392130
TI  - [Effect of terazosin on lower urinary tract function in the male decerebrate
      dog].
AB  - The effect of terazosin on the lower urinary tract function was studied by
      combined recording of bladder and urethral pressures and external sphincter
      electromyogram in 8 male decerebrate dogs. Reflex micturitions were induced by
      bladder filling before and after terazosin. The statistical analysis was carried
      out on the urodynamic parameters. During the collecting phase, terazosin at doses
      of 10, 30 and 100 micrograms/kg produced a significant decrease in maximum
      urethral pressure in the dose dependent manner. Threshold pressure was
      significantly shown to decrease at doses of 30 and 100 micrograms/kg. In the
      urodynamic parameters of the emptying phase there was a significant decrease in
      maximum contraction pressure at 10 and 30 micrograms/kg, and in voided volume at
      100 micrograms/kg. Terazosin seems to facilitate an initiation of the bladder
      contraction with a decrease in threshold pressure. In concludes that alpha 1
      adrenergic activity seems to take an important role for the maintenance of the
      urethral pressure and to control the initiation of bladder contraction in
      modulation with threshold pressure.

PMID- 1392131
TI  - [An experimental study of gastrointestinal motility during chronic large bowel
      obstruction].
AB  - Gastrointestinal motility and plasma PYY levels were investigated under chronic
      progressive large bowel obstruction in dogs. The obstruction device was applied
      around the descending colon at a laparotomy and gastrointestinal motility was
      recorded with strain gauge force transducers in the conscious state. Complete
      obstruction occurred at 26 days (21-33 days). The duration of postprandial
      interruption of motor complex (DIMC) in the antrum and duodenum were prolonged
      progressively, at partial obstruction (17.7 +/- 2.7 hr; p less than 0.05) and
      complete obstruction (23.0 +/- 4.0 hr; p less than 0.01) vs in control (13.7 +/-
      1.9 hr), while DIMC in the small bowel showed no significant changes. Progressive
      obstruction caused hypermotility in the proximal colon to the obstruction and
      hypomotility in the distal colon. These dysmotility were improved after resection
      of the obstructed segment and anastomosis. Plasma PYY levels in the fasting state
      showed no significant increase at complete obstruction (42.6 +/- 14.5 pmol/l) vs
      in control (32.9 +/- 10.2 pmol/l).

PMID- 1392132
TI  - Molecular genetics and clinical aspects of inherited disorders of nerve and
      muscle.
AB  - Rapid progress has been made in elucidating the molecular genetic basis of
      several neuromuscular disorders in the past year. Candidate genes have been
      identified or analysed in hereditary motor and sensory neuropathy (HMSN) type I,
      X-linked bulbospinal neuronopathy and non-dystrophic myotonic disorders, and
      further mutations causing amyloidosis have been identified. A familial
      amyotrophic lateral sclerosis (ALS) locus maps to chromosome 21 in some families,
      and the chronic childhood spinal muscular atrophy (SMA), facioscapulohumeral
      muscular dystrophy (FSHD) and malignant hyperthermia loci have been localized
      more precisely.

PMID- 1392133
TI  - Advances in myotonic dystrophy: a clinical and genetic perspective.
AB  - The recent identification of the gene responsible for myotonic dystrophy and the
      recognition of an expanding unstable repeat sequence as the specific molecular
      defect, have resulted in rapid changes in clinical practice as well as in our
      understanding of the disorder. Against such a framework, this review traces the
      evolution of clinical and genetic knowledge of the disorder and emphasizes the
      continuing central role of thorough clinical investigation of those at risk for
      carrying the gene as an essential element of predictive testing for myotonic
      dystrophy.

PMID- 1392134
TI  - X-linked dystrophies: from gene localization to gene therapy.
AB  - Linkage studies have narrowed the interval to which the Emery-Dreifuss muscular
      dystrophy (EDMD) gene maps, raising prospects for isolating this locus. Diagnosis
      and carrier detection for Duchenne muscular dystrophy (DMD) have been improved,
      new isoforms of dystrophin have been identified, and gene transfer studies have
      raised the prospects for gene therapy.

PMID- 1392135
TI  - Recent developments in the biology of dystrophin and related molecules.
AB  - Important progress in the understanding of various aspects of dystrophin biology
      continued during the past year. This relates to basic biochemistry, isoforms,
      subcellular localization in skeletal muscle, regional distribution in brain,
      physiological role, abnormalities caused by gene mutations and nuclear domain
      characteristics. Major progress has also taken place in the characterization of
      the dystrophin-associated glycoprotein (DAG) complex and in the understanding of
      its role in anchoring dystrophin to the plasmalemma and providing a link to the
      extracellular matrix. Characterization of the human chromosome-6-related analogue
      of dystrophin led to the discovery that in Duchenne muscular dystrophy (DMD) this
      molecule is expressed diffusely at the muscle cell surface and could, in part,
      compensate for the dystrophin deficiency of DMD.

PMID- 1392136
TI  - Mitochondrial diseases.
AB  - With the discovery of mitochondrial DNA (mtDNA) mutations in different
      neuromuscular disorders, investigations now seek to clarify how the mutant mtDNA
      induces biochemical and morphologic defects. In one of the most important
      approaches human mutant mtDNA is transferred into cells that lack mtDNA to
      examine the relationship between the amount of mutant mtDNA and defects in cell
      growth, respiration and enzyme activities. The resulting cells are 'cybrids';
      these clonal cells contain the heteroplasmic mutant and normal mtDNA from
      patients with mitochondrial diseases. The mitochondria become functionally
      defective when the amount of mutant mtDNA exceeds a certain threshold, which
      differs from mutation to mutation: 60 to 70% in chronic progressive external
      ophthalmoplegia (CPEO) and probably 95% in the syndromes of mitochondrial
      encephalopathy, myopathy, lactic acidosis, and stroke-like episodes (MELAS), and
      myoclonic epilepsy with ragged red fibers (MERRF). This threshold effect may
      explain the tissue-specific patterns of clinical expression.

PMID- 1392137
TI  - Inflammatory neuropathy: pathogenesis and clinical features.
AB  - The nature of the underlying mechanisms in inflammatory and immune-mediated
      neuropathies continues to represent an intensive area of research. Different auto
      antibodies that are thought to cause specific neuropathic syndromes have been
      described. The involvement of T cells, cytokines, complement and class II
      molecules in the pathogenesis of these syndromes has also been studied. There is
      also intensive investigation into the area of immunotherapy, in particular in the
      use of intravenous immunoglobulin (Ig).

PMID- 1392139
TI  - Spinal cord injury and its rehabilitation.
AB  - The past year has witnessed a dramatic increase in the number of studies that
      have focused on psychosocial and behavioral components of spinal cord injury
      (SCI) rehabilitation. The current article reviews and synthesizes this research
      highlighting the most important contributions to the areas of psychological
      adjustment, employment, suicide and mortality, aging, substance abuse, cognitive
      impairment, and pain management.

PMID- 1392138
TI  - Myasthenia gravis and myasthenic syndromes.

PMID- 1392140
TI  - Head injury and its rehabilitation.
AB  - Investigation of outcome following head injury is changing from studies with a
      broad scope to more focussed issues concerning specific subgroups, the
      application of new technologies such as functional brain imaging, clinical trials
      of medication, and strategies of rehabilitation. This review primarily addresses
      outcome and intervention studies relevant to the sequelae and rehabilitation of
      head-injured patients.

PMID- 1392141
TI  - Stroke rehabilitation.
AB  - Stroke produces impairments, disabilities and handicap. At each level attention
      may be directed at methods of assessment, monitoring or predicting outcome, and
      evaluating effects of treatment. There has been a change in emphasis from
      impairment to disability and handicap. The most informative research has been
      directed at evaluating rehabilitation effectiveness.

PMID- 1392142
TI  - Measurement in neurological rehabilitation.
AB  - The measurement of impairment and disability can improve patient care and is now
      essential in clinical audit. Practical, useful measures are slowly being
      developed, both for use in specific diseases and for more general use. This
      review discusses both new measures and new work on more well-established
      measures.

PMID- 1392143
TI  - Electroencephalography.
AB  - Recent advances in electroencephalography (EEG) research are presented.
      Particular emphasis is placed on sleep and epilepsy research in humans. In this
      context, among others, studies on the modifications of EEG epileptic activity
      during sleep are discussed in more detail. A large number of reports come from
      EEG monitoring during presurgical evaluation and surgical treatment of drug
      resistant epilepsy; information provided by these studies is therefore considered
      with special attention.

PMID- 1392144
TI  - Gaze and eye movement disorders.
AB  - Cortical areas were explored with regard to saccade control: the lateral
      intraparietal (LIP) area is involved in the spatial aspects of sensorimotor
      processing; the supplementary motor area in goal-directed gaze control; and from
      lesion studies; the posterior parietal cortex in triggering visually guided
      saccades. Different studies have suggested that the spatial-to-temporal
      transformation takes place in the superior colliculus (SC) and the cerebellum.
      When the vestibulo-ocular reflex (VOR) produces inadequate eye movements, other
      supplementary mechanisms (e.g. non-visual, saccade) may play a role in correcting
      gaze. A classification of central vestibular disorders of the brainstem and VOR
      has been proposed, as manifested in any one of the three major planes of action
      (yaw, pitch and role).

PMID- 1392145
TI  - Sensory evoked potentials: PERG, VEP, and SEP.
AB  - The review summarizes current developments in pattern electroretinography
      practice and theory: generator sources and clinical applications. This is
      particularly relevant to neuronal disease of the central nervous system (CNS).
      Visual evoked potentials (VEPs) are discussed in reference to the evolution and
      follow up of multiple sclerosis (MS) and in conjunction with magnetic resonance
      imaging (MRI) demonstrated abnormalities. These reveal that the techniques are
      complementary. Sensory evoked potentials (SEPs) in conjunction with MRI studies
      are highlighted as quantitatively comparable in spinal cord disorders.

PMID- 1392146
TI  - Event-related potentials.
AB  - Event-related potentials (ERPs) are scalp recorded electrophysiological responses
      that are related to an internal cognitive event. This review summarizes recent
      findings on the effects of neurologic disease and the origin of ERPs obtained in
      expectancy, attention, memory, and linguistic tasks. Cognitive ERPs allow the
      physiologic activity of the brain to be analyzed with exquisite temporal
      resolution. Our understanding of these potentials is incomplete at present.
      Advances in cognitive psychology and source localization of these surface
      potentials, however, may result in an increased understanding of both the
      organization of cognitive processing in the brain and cognitive deficits that
      result from neurologic disease.

PMID- 1392148
TI  - Neurophysiology in the science of speech.
AB  - Electrophysiological recordings of the muscles involved in speaking (respiratory,
      glottal, oromandibular) have been added to the acousticograms (ACGs) for
      analyzing the latency times in verbal reactions, their coordination and their
      patterns. The electromyogram (EMG) has allowed to better identify the preparatory
      initiation and the modulation of the muscular stiffness. Meaningful changes have
      been obtained in aging processes, stuttering, and several neurological diseases.
      Event-related brain potentials have also been investigated during normal speaking
      and reading.

PMID- 1392147
TI  - Neuro-ophthalmology.
AB  - The anatomy, neurophysiology, semiology, and pathology of the pupillary reflexes
      are reviewed. Recent advances in the demonstration of midbrain pathways
      projecting to and from the Edinger-Westphal (EW) nucleus are discussed.
      Observations of the pupillary diameter and reflexes in premature infants can be
      helpful in the diagnosis of neurological disorders. A relative afferent pupillary
      defect (RAPD) without visual disturbances can be suggestive of midbrain lesions.
      Automated pupil perimetry is proposed as an objective method for the evaluation
      of the visual field. Tonic pupil, the pupil in diabetics, and blue-cone
      monochromatism are also discussed.

PMID- 1392149
TI  - Neuromuscular disease.

PMID- 1392150
TI  - Neurological rehabilitation.

PMID- 1392151
TI  - [Current data on GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) in
      acute myeloid leukemia].
AB  - GM-CSF (Granulocyte-Macrophage Colony Stimulating Factor) activates neutrophil,
      eosinophil, granular, and macrophage precursors through binding to specific
      receptors. GM-CSF receptor is a member of the "cytokine receptor superfamily",
      which displays a particular transmembrane structure. It is expressed in small
      amounts on normal mature blood or medullary cells, with a high affinity. On acute
      myeloid leukemia blasts (18 patients), our results agree with the review of the
      literature: GM-CSF receptors are in small amounts, of two types (high and low
      affinity), with no relation to the FAB classification of leukemias.

PMID- 1392152
TI  - [Growth factors of cultured epithelial cells of breast diseases and breast
      carcinoma].
AB  - Primary cultures of non-malignant human breast tissues, benign mastopathies and
      breast carcinomas were raised in defined culture conditions and characterized for
      in vitro cell proliferation. Although some mastopathies had estradiol receptors
      they did not respond to hormone treatment. Epidermal growth factor (EGF) was
      capable of stimulating the 3 types of primary culture. In contrast,
      dexamethasone, insulin and transferrin stimulated only the proliferation of some
      benign mastopathies and carcinoma cells. Cholera toxin increased the cell growth
      of normal tissues and mastopathies but not of carcinoma in primary cultures.
      Taken together, these results show that epithelial cells from mastopathies differ
      from one another; some are similar to non-malignant cells, whereas others are
      comparable to tumor cells.

PMID- 1392153
TI  - [Cancerology training in France].
AB  - During the last years, training in cancerology in France has been developed
      extensively. The importance of training as a major element in the fight against
      cancer is now widely recognized. Cancerology teaching has been improved in the
      curse of clinical science for medical students as well as the training of general
      practitioners. Special courses qualifying for the Diploma of Specialised
      Complementary Studies in Oncology are available to Cancerologists. While
      appreciating the positive aspects of cancerology training at these different
      levels, we must stress a certain number of weak points that need to be corrected.
      Several propositions tending to further improve cancerology training are
      proposed. The implementation of these recommendations should allow France to
      maintain its rightful place in cancerology within the European Community.

PMID- 1392155
TI  - [A study of VMMC protocol (vindesine, mitoxantrone, mitomycin C) as a salvage
      chemotherapy in advanced breast cancers].
AB  - One hundred and three patients previously treated with chemotherapy including an
      anthracycline were entered in a VMMC protocol study: vindesine (Eldisine),
      mitoxantrone (Novantrone) and mitomycin C (Ametycine). Group A consisted of 41
      women who received the protocol published by Belpomme: vindesine (2.5 mg/m2 day 1
      and 8) and mitoxantrone (12 mg/m2/day) every 4 weeks, and mitomycin C (8 mg/m2)
      every 8 weeks. Group B consisted of 62 patients who were treated with a modified
      protocol: vindesine (2.5 mg/m2) and mitoxantrone (12 mg/m2) every 3 weeks on day
      1, and mitomycin C (8 mg/m2) every 6 weeks. Tolerance was acceptable with 79% of
      patients complaining of weakness. There was a 66% incidence of gastro-intestinal
      toxicity, a 10.7%-incidence of neurotoxicity (reversible dysethesias), and a 5.8%
      incidence of cardiotoxicity. There was considerable hematotoxicity of grade 2, 3
      and 4: neutropenia 16.6%, thrombocytopenia 7.7%, anemia 21.4%. There was a 19.2%
      overall objective response rate (CR and PR) (95% confidence interval: 12-30) (CR:
      3.2%). The median duration of the response was 39 weeks. There was no significant
      difference in response rates whether or not the patients (19 cases) were
      undergoing simultaneous hormonal therapy and no difference according to the
      protocol used. Similarly, neither menopause nor a previous response to
      anthracyclines had any effect on the response rate. The 19.2% response in this
      protocol is similar to other breast cancer salvage chemotherapy protocols for
      patients who have failed to respond to anthracyclines (< 20%).

PMID- 1392154
TI  - [Ewing's sarcoma of bone in adults: an anatomic-clinical study of 30 cases].
AB  - The records of 30 adult patients with Ewing's sarcoma (ES) of bone treated
      between 1980 and 1990 at the Institut Curie were studied retrospectively; the
      diagnosis was reevaluated by histological and immunohistochemical analysis, using
      HNK and anti-neuron specific enolase (NSE) antibodies. The immunohistological
      analysis disclosed a significant staining of neoplastic cells in only few of our
      cases and is therefore of limited interest in the diagnosis of ES. Three groups
      of patients have been considered according to their clinical presentation: axial,
      peripheric and initial metastatic disease. The global prognosis is poor: the
      survival rate is 70% after a follow-up period of one year, and 23% after three
      years. The evolution was severe for patients with pelvic localization and/or
      initial metastatic disease. In contrast, five of six patients who are currently
      free of disease after a mean follow-up period of 42 months presented initial
      peripheric lesion. Four of these six patients were treated by a combination of
      surgical, chemical and radiation therapies.

PMID- 1392156
TI  - [Role of radiotherapy in the treatment of bone metastases].
AB  - The most frequently encountered metastases during evolution of cancers are bone
      metastases, which involve painful syndrome. External radiotherapy is an effective
      and indisputable treatment to give relief to suffering patients. The modalities
      of the regimen of external radiotherapy are different according to the disease
      stage, the prognosis and eventually associated treatments such as chemotherapy,
      hormonotherapy or surgery. The dose can be delivered either according to normal
      regimen, hypofractionated radiotherapy, or half-body radiotherapy. Whatever the
      modalities, antalgic results noted in around 85% cases are very similar. On the
      other hand, the plastic action of external radiotherapy on lytic bone is also
      important.

PMID- 1392158
TI  - [Measurement of quality of life. Application to the screening of psychological
      distress in cancer patients].
AB  - As cancer treatments are becoming more and more traumatic the quality of life of
      these patients must be taken into consideration. This study was set up in 1982
      and aimed at screening patients suffering from major psychological distress using
      a quantitative assessment of the quality of life. A self-administered
      questionnaire (QLQ) and linear analogues (LA) were developed and validated. The
      patient's acceptance of these two measuring instruments was tested on a sample
      group of patients in the Oncology Department of Besancon University Hospital and
      gave a result of 94% which was higher than that of a psychological interview
      (64%). A comparison of the assessment of the quality of life by the patient, the
      psychologist and the physician is an important phase in this concept. Agreement
      by the doctor and the patient using the Karnofsky indices was moderate (62% of
      the cases using a simplified scale): patients tended to overstate the extremes.
      The overall scores and the different questionnaire items completed by the patient
      and the psychologist were correlated, but agreement varied according to each
      item. An attempt was made to establish a predictive value for the questionnaire
      and the linear analogues to identify patients suffering from major psychological
      distress and requiring psychosocial support by comparing the results of the tests
      with the assessment of the psychologist during an interview. A stepwise
      logistical regression selected a combination of three items which screened more
      than 80% of these patients. The linear analogues were not sufficiently
      discriminatory to be used. The overall results suggest that a quality of life
      measurement can be integrated into daily clinical practice.

PMID- 1392157
TI  - [Laser therapy in the prevention and treatment of mucositis caused by anticancer
      chemotherapy].
AB  - The appearance of mucositis is a frequent and painful secondary effect of
      anticancer chemotherapy. Patients who develop oral toxicity during the first
      course of treatment will almost assuredly show identical side effects during each
      subsequent course unless the drugs are changed or the doses are lowered. In the
      absence of an efficacious antidote or preventive prophylaxis for such lesions to
      date, this report presents the results of a preliminary retrospective non
      randomized study of the effect of soft-laser treatments on mucositis in cancer
      patients receiving combination chemotherapy, including 5-fluorouracil. Iatrogenic
      mucositis was observed during 43% of 53 chemotherapy cycles in the case control
      population. Curative laser therapy reduced the time to repair lesions and the
      rate of therapeutic modifications. For patients who received soft-laser therapy
      as a preventive measure, the incidence of oral complications was reduced to 6%
      during 101 cycles of chemotherapy. All of these patients, even those who have
      encountered mucositis before receiving preventive laser therapy, terminated their
      cancer therapy as originally scheduled. Well designed and carefully controlled
      trials will be necessary to define the place of helium-neon laser therapy in the
      repair and prevention of oral complications due to cancer chemotherapy.

PMID- 1392159
TI  - [Application of Huriet's law: a progress in cancer therapy?].

PMID- 1392160
TI  - [Matrix metalloproteinases and cancer. Role and control].

PMID- 1392161
TI  - [Radiotherapy vs. chemotherapy in early-stage Hodgkin's disease: a justified
      approach?].

PMID- 1392162
TI  - [Multiple myeloma: current therapeutic approaches].
AB  - The therapeutic strategy in multiple myeloma depends on age and tumor mass. Stage
      I must not be treated. The Melphalan Prednisone regimen is the reference for
      induction therapy because polychemotherapies are generally not superior. At this
      phase, the addition of Interferon alpha seems to be interesting. This drug has an
      important role during the steady-state phase. VAD represents the most efficient
      chemotherapy. Body hemi-irradiation is also useful. The analgesic effect and the
      decrease in the tumoral mass are the striking effects of this treatment. In young
      patients, high dose chemotherapy with bone marrow transplantation is proposed.
      Verapamil and anti-IL6 antibodies are currently being evaluated. Symptomatic
      treatment is essential in this non curable disease.

PMID- 1392163
TI  - [Statcan: a telematic system for checking mortality and incidence of cancer in
      France].
AB  - Statcan is an interactive system for consulting cancer mortality and incidence
      data in France. This system is accessible through the Minitel network and
      provides information concerning cancer mortality: number of deaths, basic rates,
      standardized rates for the French, European and world population, cumulative
      rates up to the age of 74 years as well as specific rates by age, sex and cancer
      site for France as a whole from 1968 to 1988 and by region for 1968, 1975 and for
      1979-1988. National incidence data are available for 5 regions between 1978 and
      1982. several complementary chapters provide information explaining the
      methodology used and help in formulating the questions.

PMID- 1392164
TI  - [FGFB binding sites in cancers of the human breast].
AB  - We investigated binding characteristics of bFGF in membranes prepared from 4
      human breast cancer cell lines (MCF-7, T-47D, BT-20 and MDA-MB-231) and 38
      primary breast cancer biopsies. Results of competitive binding experiments were
      analysed using the "Ligand" program to determine binding site concentrations and
      affinities. bFGF mitogenic activity was also measured by [3H]-thymidine
      incorporation into DNA of breast cancer cell lines. The presence of high-affinity
      binding sites was demonstrated in each cell type (Kd: 0.5 nM). The presence of
      these high-affinity binding sites was confirmed by saturation experiments. A
      second class of low-affinity binding sites was detected in the 2 hormono
      independent cells (BT-20: Kd = 2.9 nM; MDA-MB-231: Kd = 2.7 nM). bFGF stimulated
      the proliferation of MCF-7, 7-47D, BT-20 and not of MDA-MB-231 cell lines. In
      breast cancer biopsies, binding sites were detectable in 36/38 cases; high
      affinity binding sites (Kd < 1 nM) were present in 19/39 cases and low-affinity
      binding sites (Kd > 2 nM) were present in 29/36 cases (the 2 classes of binding
      sites were present in 12 biopsies). No relation between FGF binding sites and
      node involvement nature or grade of tumor was evidenced. Negative correlations
      (Spearman test) were found between total bFGF binding site concentrations and
      estradiol receptor concentrations (P = 0.05) or progesterone receptor
      concentrations (P = 0.009). The demonstrations of 1), bFGF specific binding sites
      in breast cancer membranes; and 2) bFGF growth stimulation of some breast cancer
      cell lines, indicate that this factor could be involved in the growth of most
      breast cancers, and could act (among other factors) directly on the growth of
      cancer cells.

PMID- 1392165
TI  - Immunolocalization of matrix metallo-proteinases and their tissue inhibitor in
      human mammary pathology.
AB  - Matrix metallo-proteinases (MMPs) are a group of enzymes thought to be
      responsible for both normal connective tissue matrix remodelling and accelerated
      breakdown associated with tumor development. The distribution of 3 major matrix
      metallo-proteinases was studied in human mammary pathology: collagenase (MMP1)
      which degrades fibrillar interstitial collagens, a 72-kDa gelatinase (MMP2) which
      mainly degrades type IV collagen and denatured collagens, and stromelysin (MMP3)
      which has a wider range of action, degrading several matrix components including
      the core proteins of proteoglycans, laminin and non-helical regions of collagens.
      These MMPs and the MMP tissual inhibitor (TIMP1) were detected by
      immunohistochemistry in 30 benign and 79 malignant lesions of the breast. MMPs
      were detected in 1 fibroadenoma (collagenase) and 22 breast carcinomas:
      collagenase (9 cases), stromelysin (12 cases) and gelatinase (16 cases) with a
      limited distribution. Tumor cells were preferentially labelled and the
      localization of gelatinase and stromelysin at the periphery of some non-invasive
      and well-differentiated clusters supports the role of these enzymes in the
      breakdown of basement membranes. Only a few stromal cells (fibroblasts) were
      found to be immunopositive. In contrast, TIMP1 was more frequently detected, and
      was found in 7 benign lesions and 55 carcinomas out of 79. It was mainly
      localized at the periphery of the endothelial cells but was occasionally detected
      in cancer cells and fibroblasts.

PMID- 1392166
TI  - Tumor associated glycoprotein-72 (TAG-72) levels in patients with non-malignant
      and malignant disease.
AB  - TAG-72 is a tumor-associated antigen identified by the monoclonal antibody B72.3.
      Serum levels of TAG-72 were measured in patients with non-malignant and malignant
      disease. TAG-72 is not a specific marker of cancer and slightly elevated levels
      of this antigen can also be detected in the serum of healthy subjects. However,
      our results show that specificity (92%) and positive predictive value (86%) of
      this marker are very high. TAG-72 levels above the cut-off limit of 6 U/mL were
      found in patients with tumors of various organs, including gastrointestinal,
      ovarian, lung and breast cancer. TAG-72 assay sensitivity is related to tumor
      stage with values being highest with advanced disease, especially in patients
      with gastric cancer and lung adenocarcinoma.

PMID- 1392168
TI  - [Lymph node metastasis of melanoma of unknown primary tumor].
AB  - Sixteen patients with clinical stage II melanoma of unknown primary site
      (regional lymph node metastasis) were followed up between 1978 and 1988. The 5
      year survival rate was 47%. These results seem to parallel those for stage II
      disease with known primary tumor sites, as has been observed in other data from
      the literature. The hypotheses put forward to explain such lesions are the
      spontaneous regression of the primary tumor, and the onset of primary malignant
      melanoma in the lymph nodes.

PMID- 1392167
TI  - [Current role of chemotherapy in the treatment of invasive cancers of the
      bladder].
AB  - Treatment of bladder carcinoma with cystectomy and or radiotherapy provide 5-year
      survival rates of 28-50%. Phase II chemotherapy trials have proven its efficacy
      with a partial and complete response rate of 20% and 10% respectively for drugs
      such as cisplatin or methotrexate. Recent phase III studies have demonstrated the
      superiority of associations such as CMV, CISCA or M-VAC with complete response
      rates of 28-39%. Neoadjuvant chemotherapy may increase local control and offer
      the possibility of conservative treatment after complete tumor regression (one
      third of cases). The positive effect of neoadjuvant chemotherapy on survival has
      not yet been demonstrated and randomized trials are now in progress. The
      concomitant association of cisplatin or fluorouracil with radiation therapy
      provides high complete response rates (65-88%) in all published studies. A longer
      follow-up period is necessary to confirm these results in terms of local control
      gain and survival benefit, but this strategy seems to constitute a major
      advancement for patients unable to undergo radical cystectomy. Further studies
      are needed before extending this conservative approach to less advanced invasive
      bladder carcinoma. Adjuvant chemotherapy may decrease metastasis rate, but
      survival benefit has not yet been definitively established by randomized studies.

PMID- 1392169
TI  - [Adjuvant tamoxifen in breast cancers with negative estrogen receptors. Complete
      review of the literature].

PMID- 1392170
TI  - [Acute lymphoblastic leukemia and pregnancy. Apropos of a case].
AB  - The authors report on a case of a woman with acute lymphoblastic leukemia treated
      with cortisone therapy during pregnancy. No problems were encountered during the
      gestational period or at parturition; and no maternal or neonatal complications
      were observed.

PMID- 1392172
TI  - Overall clinical effect of percutaneous coronary angioplasty: a critical analysis
      by follow-up and long-term angiography.
AB  - In order to determine the clinical efficacy of coronary angioplasty, the outcome
      was analyzed in 557 patients who underwent initial angioplasty prior to the end
      of 1987. Primary success (reduction of stenosis greater than or equal to 20% and
      residual stenosis less than 50%) was achieved in 492 (88.3%) of the patients.
      Follow-up angiography showed patency (stenosis less than or equal to 50%) in 295
      or 60.0% of the 471 patients and ultimate lesion patency was achieved by
      repeating angioplasty up to 4 times in 425 (91.4%) of 465 patients followed
      angiographically. At the 3-year angiography performed in 209 patients with patent
      lesions, only 2 patients exhibited progression of their disease at dilated sites,
      while 48 had new lesions. Taking into consideration the 55 patients with
      unsuccessful primary angioplasty, 10 patients with major complications and 9
      patients with mild restenosis, 434 out of 530, or 81.9% of the patients appear to
      have benefited from angioplasty.

PMID- 1392171
TI  - Effects of metabolic control on ventricular function in type 2 diabetic patients.
AB  - The effects of the metabolic changes of type 2 diabetic patients on ventricular
      function, especially diastolic ventricular function were investigated. An
      examination was performed before and after treatment of 18 diabetic patients
      divided into 3 groups: insulin therapy, oral hypoglycemic drugs and diet therapy
      (6 patients each). The results indicated that both systolic and diastolic
      ventricular dysfunctions observed were improved by the correction of
      hyperglycemia. Therefore it is necessary to treat diabetes mellitus as early as
      possible for the prevention of both cardiac dysfunction and microangiopathy.

PMID- 1392173
TI  - Urinary 11-dehydro-thromboxane B2: a quantitative index of platelet activation in
      cerebral infarction.
AB  - Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with
      chronic cerebral infarction, patients under chronic aspirin treatment and
      patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite
      of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis
      was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in
      patients with cerebral infarction and distinct carotid-atherosclerotic lesions
      (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than
      0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients
      with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g
      creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less
      than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers
      (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2
      excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial
      fibrillation showed very high values. Our results indicated that platelet
      activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro
      TXB2 is the appropriate analytic target for detecting platelet activation.

PMID- 1392174
TI  - Hospital-onset tuberculosis in compromised host.
AB  - A total of 21 patients developed active tuberculosis (TB) during hospitalization.
      Active TB was identified by bacteria-positive, biopsy or autopsy. Infection was
      confirmed to the lung, pleura, lymph node and miliary lesions and 7 patients had
      open tuberculosis. In half of the patients, chest X-ray films demonstrated
      unusual findings in adult tuberculosis: lower lung field pneumonia and miliary
      pattern. All the patients suffered from severe underlying diseases and an
      intensive therapy with steroid, immunosuppressive agents, antitumor drugs,
      radiation and operation was found as predisposing factors for TB occurrence. Nine
      patients recovered from current infection with anti-tuberculosis drugs; 14
      patients died and TB directly caused death in 8 patients. These data strongly
      suggest that TB is one of the most important infections in compromised hosts. We
      emphasize that this infection presents a serious clinical problem in a general
      hospital today.

PMID- 1392175
TI  - Abnormalities in platelets and vascular endothelial cells induced by glycated
      lipoproteins.
AB  - We studied the effects of glycated lipoproteins of low- and high-density (LDL and
      HDL) on platelets and vascular endothelial cells. After pretreatment for 5
      minutes at 37 degrees C, the thrombin-induced synthesis of thromboxane B2 in
      washed platelets was significantly increased by glycated LDL as compared with
      native LDL (198.9 +/- 16.2 vs 90.3 +/- 29.4 ng/10(9) platelets, n = 8, p less
      than 0.01). Platelet aggregation was also increased by glycated LDL as compared
      with native LDL. After treatment with platelet-rich plasma for 5 hours at 37
      degrees C, these values were suppressed by native HDL vs the control (buffer),
      but not by glycated HDL. Abnormalities in the release of 6-keto prostaglandin F1
      alpha and lactate dehydrogenase from vascular endothelial cells were also induced
      by glycated LDL and/or HDL. These observations suggest that abnormalities induced
      in platelets and vascular endothelial cells by glycated lipoproteins may play an
      important role in the development of atherosclerosis in patients with diabetes
      mellitus.

PMID- 1392176
TI  - Simultaneous measurements of adenosine deaminase activity and tuberculostearic
      acid in pleural effusions for the diagnosis of tuberculous pleuritis.
AB  - Adenosine deaminase (ADA) activity and tuberculostearic acid (TSA) levels in
      pleural effusions were measured in 18 patients with active tuberculous pleuritis,
      16 patients suspected of having tuberculous pleuritis, 14 patients with
      carcinomatous pleuritis, and 19 patients suffering from pleuritis of non
      malignant and non-tuberculous etiology. In the patients with active tuberculous
      pleuritis, ADA was elevated in 56% and TSA was positive in 78%. In 83% of these
      patients, either ADA was elevated or TSA was positive. ADA was elevated together
      with a positive TSA in 50%. In contrast, TSA was positive in only 6% and ADA was
      elevated in 24% of the patients with non-tuberculous pleuritis, and none of these
      patients showed the combination of an elevation of ADA and a positive TSA. These
      results suggest that simultaneous measurements of both ADA and TSA in pleural
      effusions are useful for the diagnosis of tuberculous pleuritis.

PMID- 1392177
TI  - Seven patients with plasma cell granuloma (inflammatory pseudotumor) of the lung,
      including two with intrabronchial growth: an immunohistochemical and electron
      microscopic study.
AB  - Seven patients (mean age, 50.7 +/- 20.4 years; range 21-77) with plasma cell
      granuloma (PCG) of the lung are reported. Cough and sputum were the most common
      presenting symptoms, followed by fever. Elevated erythrocyte sedimentation rate
      and serum C-reactive protein levels were found in all patients tested.
      Radiologically, five cases presented as solitary, well-circumscribed masses and
      two as ill-defined, pneumonia-like densities. One showed focal calcification. No
      predilection of occurrence was observed in either lobe of the lung.
      Histologically, the lesions consisted of a proliferation of mature plasma cells
      and reticulo-endothelial cells supported by a stroma of granulation tissue, with
      varying degrees of myxoid change or collagenization. Angioinvasion within the
      lesion was observed in 4 of the 7 cases. Immunohistochemical staining revealed
      the IgG-predominant polyclonal nature of the plasma cells, indicating a reactive
      inflammatory process rather than a neoplastic one. Electron microscopy confirmed
      the benign nature of the plasma cells with fibroblast and myofibroblast
      proliferation admixed with that of other inflammatory cells.

PMID- 1392179
TI  - Lung cancer accompanied by erythema.
AB  - Skin manifestations associated with malignant diseases are designated syndroma
      dermatotumorale. A case of lung cancer combined with atypical erythema is
      reported. A 70-year-old man was admitted to hospital because of a 4-month history
      of atypical erythema of unknown origin. A nodule in the right lung was revealed
      on chest roentgenogram which was diagnosed as lung cancer. After right upper
      lobectomy, the erythema regressed gradually and disappeared completely in 7 days.
      It is suggested that the erythema was a manifestation associated with the lung
      cancer.

PMID- 1392178
TI  - Humoral and cellular immunity to Candida albicans in patients with bronchial
      asthma.
AB  - Delayed cutaneous reactivity to Candida albicans (C. albicans) and PPD (purified
      protein derivative) was examined in 52 patients with bronchial asthma in relation
      to the production of specific IgG4 antibodies against the antigen. 1. The
      frequency of a positive, immediate skin reaction to C. albicans was similar among
      the five age groups, ranging from 60.0% to 66.7%. 2. The incidence of a positive
      delayed skin reaction to C. albicans was lower in patients between the ages of 10
      and 30 and tended to decrease with aging in the patients over the age of 51. 3. A
      delayed skin reaction to PPD was positive in patients between 31 and 50 with a
      higher incidence; this incidence decreased in patients over age 51. 4. The level
      of C. albicans-specific IgG4 antibodies was significantly higher (26.7 u/ml) in
      patients with a negative delayed skin reaction to the antigen than in those with
      a positive reaction (5.9 u/ml) (p less than 0.001). There was no correlation
      between delayed skin reaction to PPD and production of specific IgG4 antibodies.

PMID- 1392180
TI  - Kawasaki disease complicated by acute myocardial infarction due to thrombotic
      occlusion of coronary aneurysms 19 years after onset.
AB  - A 25-year-old man with a history of Kawasaki disease from the age of 7 had acute
      inferior myocardial infarction. Emergency right coronary arteriogram showed
      successive coronary aneurysms at the proximal to middle portion of the right
      coronary artery, and total occlusion at the proximal segment. Intracoronary
      thrombolysis was performed and the right coronary artery was recanalized. On left
      coronary arteriography, coronary aneurysms and mild localized stenoses at the
      inlet and outlet of the aneurysms were found. It was suggested that the
      myocardial infarction was caused by thrombotic occlusion of coronary aneurysms
      complicated with Kawasaki disease.

PMID- 1392181
TI  - Systemic lupus erythematosus with sensorineural hearing loss and improvement
      after plasmapheresis using the double filtration method.
AB  - A 32-year-old female was diagnosed as having systemic lupus erythematosus based
      on her laboratory tests. In 1985 she began to complain of hearing difficulty. Her
      hearing ability deteriorated to the extent that her audiogram revealed a hearing
      loss of 90 db to 110 db in both ears in September 1989. She received two series
      of plasmapheresis treatments using the double filtration method. After two series
      of plasmapheresis treatments, her hearing improved dramatically. This improvement
      suggests that circulating immune complexes and anti-phospholipid antibodies might
      play a pathological role in the hearing impairment in SLE patient.

PMID- 1392182
TI  - Heterotopic intestinal membrane in a retroperitoneal tumor.
AB  - Plain abdominal X-rays of a 13-year-old girl with chief complaints of back pain
      revealed calcification in the upper left abdomen. A calcified tumor was confirmed
      at the dorsal side of the pancreatic tail upon admission. A completely formed
      colic membrane free of all other germ layers was discovered within the tumor,
      leading to a diagnosis of heterotopic colonic membrane. To our knowledge, there
      have been no other cases of heterotopic intestinal tissue of this type, so we
      consider this an extremely rare case worth reporting.

PMID- 1392183
TI  - Recurrent intracranial hemorrhagic episodes in hepatopulmonary syndrome.
AB  - A 57-year-old woman with hepatopulmonary syndrome was treated for eight years.
      Severe hypoxemia continued and her erythrocytosis was slowly progressive. Two
      episodes of intracranial hemorrhagic attack had occurred during the follow-up
      period and the patient died due to multiple organ failure after the second
      intracranial hemorrhage. Her autopsy findings confirmed not only established
      liver cirrhosis associated with intracranial hemorrhage but also the marked
      dilatation of pulmonary capillaries in both lungs. These findings suggest that
      secondary erythrocytosis in hepatopulmonary syndrome can be contributed to fatal
      intracranial vascular accidents. The containment of erythrocytosis should be
      considered in these patients.

PMID- 1392184
TI  - Aseptic necrosis of unilateral scaphoid bone in systemic lupus erythematosus.
AB  - An SLE patient developed aseptic necrosis of the right scaphoid bone 4 years
      after an episode of aseptic necrosis of bilateral femoral heads caused by
      corticosteroid treatment. Since the aseptic necrosis of the right scaphoid bone
      was preceded by the insidious exacerbation of SLE as evidenced by facial
      erythema, it was considered to be a result of vasculopathy due to active SLE. It
      took 14 months to make a correct diagnosis of the aseptic necrosis of the
      scaphoid bone by a chanced roentgenogram for the routine evaluation for
      osteoporosis. Therefore, the importance of an awareness of this possibility and
      repeated radiographic examinations is emphasized for the correct diagnosis of
      joint manifestations in SLE.

PMID- 1392185
TI  - Renal handling of urate in two patients with hyperuricemia and primary
      hyperparathyroidism.
AB  - Two patients with primary hyperparathyroidism had hyperuricemia due to the
      decrease in urate clearance. In analysis by 4-component model system, the tubular
      secretion of urate commonly decreased without changes in either filtered urate or
      presecretory reabsorption of urate. Both patients had a reduction of urea
      clearance, and both parathyroidectomy in the former case and intravenous infusion
      of saline in the latter case could reduce the serum urate level associated with
      the increase in the ratio of urate clearance to creatinine clearance. It is of
      interest that the former case with a higher serum urate level had a relatively
      higher postsecretory reabsorption, even with the decrease in tubular secretion of
      urate. However, the latter patient with a lower serum urate level had a decrease
      in postsecretory reabsorption of urate in proportion to the decrease in tubular
      secretion. These results suggest that in hyperuricemia patients with primary
      hyperparathyroidism, the reduction of tubular urate secretion via hypoperfusion
      of the capillary network is typically present, however, the severity of the
      hyperuricemia might be dependent on the dysfunction of the postsecretory
      reabsorption of urate.

PMID- 1392186
TI  - Adult Still's disease with myocarditis and peritonitis.
AB  - A 26-year-old woman had myocarditis and peritonitis during an acute multisystem
      attack of Still's disease. To our knowledge, these complications are rare
      manifestations of adult Still's disease. Treatment with high-dose
      adrenocorticosteroids was rapidly successful in controlling these manifestations.

PMID- 1392187
TI  - Hypomagnesemia with increased metabolism of parathyroid hormone and reduced
      responsiveness to calcitropic hormones.
AB  - A patient with severe hypomagnesemia due to chronic alcoholism is presented who
      repeatedly exhibited marked hypocalcemia with a dissociation between
      radioimmunoassay findings for mid region of parathyroid hormone (PTH-M) and
      immunoradiometric assay findings of serum intact PTH (PTH-intact). Serum PTH-M
      was moderately elevated whereas serum PTH-intact was in a low normal range every
      time when her serum magnesium (Mg) concentration was markedly reduced. There was
      also a marked reduction in serum osteocalcin concentration. Supplementation of Mg
      resulted in a sharp increase in serum PTH level with a rapid disappearance of the
      dissociation between the two immunoassays of PTH. Shortly after serum PTH and
      1,25(OH)2D levels reached their peak, serum osteocalcin started to increase, and
      was elevated into a supranormal level with normalization of serum Ca
      concentration. Mg is thought to act as a mimic/antagonist of calcium (Ca), and
      high extracellular Ca is shown to cause an inhibition of secretion with a
      stimulation of degradation of PTH. Thus, these observations are consistent with
      the hypothesis that Mg deficiency causes an increase in the metabolism of PTH and
      a reduction in the secretion of bioactive intact PTH by increasing the
      sensitivity of parathyroid cells to Ca. In addition, the fact that hypocalcemia
      disappeared concomitant with a marked increase of serum osteocalcin from
      undetectable levels suggest that refractoriness of bone to calcitropic hormones
      is present which plays a significant role in the development of hypocalcemia
      under hypomagnesemia, and that serum osteocalcin can be a good marker for the
      assessment of the responsiveness of bone to calcitropic hormones in these
      patients.

PMID- 1392188
TI  - Thymic carcinoma associated with pinealoma and terminating with peroxidase
      negative acute myeloid leukemia.
AB  - Thymoma is associated with a wide variety of syndromes. However, an association
      with peroxidase-negative acute myeloid leukemia and pinealoma, although feasible
      due to the marked influence of this tumor on the lymphoid system, has not been
      described previously. A patient with thymic carcinoma and pinealoma who developed
      peroxidase-negative acute myeloid leukemia as a late event is presented in this
      report.

PMID- 1392189
TI  - Rounded atelectasis with pleuritis: diagnosis and surgical treatment.
AB  - A 73-year-old male was admitted with a large rounded atelectasis with pleural
      effusion. The involved lung was refilled with air as soon as surgical
      decortication of the thickened visceral pleura covering it was performed.
      Surgical treatment is believed to be necessary when a large rounded atelectasis
      with pleural effusion persists for a long time, or when malignancy is not
      completely excluded.

PMID- 1392190
TI  - Chlamydia trachomatis peritonitis: report of a patient presenting spontaneous
      regression of ascites.
AB  - A 36-year-old Japanese woman complained of right hypochondralgia followed by
      ascites. Paracentesis showed a turbid, straw-colored sterile exudate. Computed
      tomography and magnetic resonance imaging of the abdomen revealed a left
      periuteric mass and ascites. The mass and ascites spontaneously regressed within
      a month with no specific treatment. Later, after the patient had been discharged
      from hospital, immunofluorescence antibody titers for Chlamydia trachomatis were
      successfully determined using stored ascitic fluid and serum. Though the number
      of cases of Chlamydia trachomatis peritonitis has increased, few cases with
      ascites have been reported, and spontaneous regression of the ascites is also
      rare.

PMID- 1392191
TI  - A new and effective purge (Golytery) for expelling tapeworms from the
      gastrointestinal tract after chemotherapy.

PMID- 1392192
TI  - Endometrial resection. A modern treatment of menorrhagia.
AB  - In general menorrhagia is poorly understood and tends to be unsatisfactorily
      treated. The word menorrhagia is derived from the Greek men month and rhegynai,
      to burst forth. Patients complain of increased menstrual loss, requiring more
      sanitary protection, or of the passage of clots. Most patients with menorrhagia
      have no significant uterine abnormality and the woman's interpretation of her
      blood loss is insufficient and unreliable. Menorrhagia must be defined in terms
      of measured menstrual blood loss. Many medications effectively diminish blood
      loss, but the symptoms usually return after the therapy has been stopped. Long
      term treatment is also restricted due to the potential side effects associated
      with some drugs.

PMID- 1392193
TI  - An African diary.

PMID- 1392194
TI  - Hungary--'egyshegedre'!

PMID- 1392195
TI  - Pre-operative assessment for Mrs Bloggs.
AB  - The pre-operative phase is the assessment phase for patients about to undergo
      surgery. This involves visiting the patient in the ward area, an opportunity for
      the patient to meet the nurse who will be responsible for their care when in
      theatre. It is also an opportunity for the nurse to assess the patient, plan care
      and give information to the patient about the operating and recovery rooms.

PMID- 1392196
TI  - The Medisafe M530 is designed to clean using ultrasonic pulses.

PMID- 1392197
TI  - To make theatre nurses increasingly aware of how others see them.

PMID- 1392198
TI  - Care plans--a personal view.

PMID- 1392200
TI  - The health of the nation.
AB  - This document, launched by the Government in July, 1992, represents the first
      national policy aimed at improving the overall health of the British population.
      It emphasises the purpose of the National Health Service--to improve health, not
      just treat sickness. This White Paper represents a beginning, with five target
      areas as priorities: Coronary heart disease and stroke; Cancers; Accidents;
      Mental illness; HIV/AIDS and sexual health

PMID- 1392199
TI  - Care plans for the operating department.
AB  - Very little, if any, of the care administered by the theatre staff within
      operating theatres has ever been fully documented. The person 'scrubbed' for the
      case and the circulating person accountable for the final swab, instrument and
      needle checks, sign their names in a ledger within theatre. A verbal exchange
      relating to the patient's operation, the dressings applied, any drains or
      implants in situ etc. may take place between the 'scub' person and the nurse into
      whose care the patient is to be entrusted. It is little wonder that we in
      theatres appear to have lost our identity as nurses and the role envisaged by our
      colleagues is one of a technician or that of being the surgeon's 'hand-maiden'!
      As stated in a previous Journal, 'The failure to define the nurse's role in the
      theatre can only mean one of two things--either nursing is not clearly
      demonstrated by theatre nurses or nursing does not exist within operating
      theatres'.

PMID- 1392201
TI  - Total patient care assessment.

PMID- 1392202
TI  - Change and the operating theatre nurse (1). The role of the nurse.
AB  - Martin Hind proposes that the role of the operating theatre nurse is in need of a
      change to a more perioperative nature that emphasizes patient-centred nursing. He
      explores the reasons underpinning the need for this change in role will be.

PMID- 1392203
TI  - Managing resources in the operating department.
AB  - A number of articles on the problems of resource management have been published
      in these pages over the past few years. Although these articles highlighted some
      of the difficulties and problems faced by theatre nurses, none actually gave a
      means of resolving them.

PMID- 1392204
TI  - An interview with ... Carol Jones. Interview by Dina Plowes.

PMID- 1392205
TI  - Intercultural communication system.

PMID- 1392206
TI  - Ethical issues.

PMID- 1392207
TI  - The patient's charter.

PMID- 1392209
TI  - The Welsh National Board framework for continuing education.

PMID- 1392208
TI  - Postoperative nausea and vomiting.
AB  - One of the most common and distressing side effects after surgery performed under
      general anaesthetic is postoperative nausea and vomiting (PONV). Indeed, for many
      patients, PONV is the most distressing feature of their operation and some may
      become anxious about having another operation because of this. The medical and
      economic consequences of PONV can also be serious. This article looks at the
      incidence, causes, and current management of PONV, and the development of a new
      drug for the prevention and treatment of this.

PMID- 1392210
TI  - Northern Ireland and nursing developments.

PMID- 1392211
TI  - ENB--continuing education for practice.

PMID- 1392212
TI  - Post-registration education and practice. The Scottish scene.
AB  - Post Registration Education has for many years been either Professional or
      Academic, however with the publication of the guidelines for P2000, many
      registered nurses have seen the two paths as one. The new education programmes
      for the Diploma of Higher Education in Nursing will commence throughout Scotland
      in August or September of this year.

PMID- 1392213
TI  - 'Something for your pain, dear'?
AB  - As a student nurse in the middle '70s, I recall being struck by the
      unsophisticated and somewhat haphazard way pain relief following surgery was
      managed. I had been expecting to receive tuition in the clinical environment, as
      my classroom studies had not included any reference to pain or pain management. I
      was, like other staff on the ward, largely ignorant of pain physiology and pain
      psychology, and accustomed to making subjective judgement of other people's pain,
      based largely on my own misconceptions and inappropriate inherited attitudes.
      This, in turn, led to analgesia being offered in much the same way as a 'nice cup
      of tea', 'Something for your pain, dear?' Standard doses of analgesia were
      prescribed for the majority of patients via intramuscular or oral routes, and the
      actual dose administered was randomly selected by nursing staff and delivered at
      varying intervals. Thankfully, over the last few years, things have started to
      change.

PMID- 1392214
TI  - Burnout and risk factors for cardiovascular diseases.
AB  - The burnout syndrome denotes a constellation of physical fatigue, emotional
      exhaustion, and cognitive weariness resulting from chronic stress. Although it
      overlaps considerably with chronic fatigue as defined in internal medicine, its
      links with physical illness have not been systematically investigated. This
      exploratory study, conducted among 104 male workers free from cardiovascular
      disease (CVD), tested the association between burnout and two of its common
      concomitants--tension and listlessness--and cardiovascular risk factors. After
      ruling out five possible confounders (age, relative weight, smoking, alcohol use,
      and sports activity), the authors found that scores on burnout plus tension
      (tense-burnout) were associated with somatic complaints, cholesterol, glucose,
      triglycerides, uric acid, and, marginally, with ECG abnormalities. Workers
      scoring high on tense-burnout also had a significantly higher low density
      lipoprotein (LDL) level. Conversely, scores on burnout plus listlessness were
      significantly associated with glucose and negatively with diastolic blood
      pressure. The findings warrant further study of burnout as a predictor of
      cardiovascular morbidity and mortality.

PMID- 1392215
TI  - Coronary heart disease risk scales and reactivity in a prevention program
      assessment: failure to show positive relationships.
AB  - This study was designed to evaluate relationships among the Jenkins Activity
      Survey, the Cook-Medley Hostility Scale, and cardiovascular reactivity measured
      during a semistructured interview in a hospital setting. Subjects were 201
      business persons participating in a cardiovascular risk assessment interview
      component of a fitness program. Correlation analysis showed little evidence of
      significant positive relationships between self-report scores and reactivity in
      the total sample and among subjects with high resting blood pressures. Graphic
      analysis of total sample bivariate distributions, however, demonstrated patterns
      suggestive of nonlinear relationships. Evaluation of scatterplots and residual
      plots in conjunction with nonlinear and weighted least squares regression
      analyses nonetheless failed to reveal significant nonlinear relationships. The
      authors discuss implications of these findings.

PMID- 1392216
TI  - Anger expression, hostility, anxiety, and patterns of cardiac reactivity to
      stress.
AB  - The majority of studies investigating the relationships between psychological
      characteristics and cardiovascular reactivity to stress use a research strategy
      in which discrete traits are evaluated in isolation. The present study examined
      the effects of additive and/or interactive relationships among traits on cardiac
      reactivity to a mental arithmetic task. In addition, impedance cardiographic
      techniques were employed to examine potential relationships between such
      psychological traits and a specific measure--pre-ejection period (PEP)--of
      sympathic influence on the heart. Forty-nine undergraduate men performed a mental
      arithmetic task while continuous measures of PEP and interbeat interval (IBI)
      were collected. The subjects then completed questionnaires measuring anger
      expression, hostility, and trait anxiety. Analyses of variance (ANOVAs) showed a
      significant main effect for anger-out on PEP change from baseline, but not for
      IBI. Results also showed that anger-in interacted with anger-out and hostility to
      affect both PEP and IBI changes significantly. Other results indicated that
      subjects in the high anger-in/low anger-out and high anger-in/low hostility
      groups did not show significant PEP change, although they nevertheless showed
      significant IBI change. These results highlight the importance of the
      consideration of interactions among traits in predicting cardiac reactivity and
      of the importance of measuring specific indexes of sympathetic arousal.

PMID- 1392217
TI  - Stress, anxiety, and cognitive buffering.
AB  - Cognitive theories of psychopathology and therapy maintain that attitudes and
      beliefs mediate one's affective responses to life events. Anxiety and depression
      are thus consequences, not of an individual's circumstances, but of the
      distorted, irrational perspective from which these are viewed. Similarly,
      although less often considered, adaptive cognitions should serve as buffers
      against stressful life events. This proposition has received little attention,
      and the single study that attempted to address it directly failed to do so. The
      present investigation sought to reassess the buffering hypothesis. Ninety-seven
      subjects were evaluated as to (1) the levels of stress they had experienced in
      the recent past; (2) their current feelings of anxiety and depression; and (3)
      the extent to which they endorsed illogical, unrealistic attitudes. Dysfunctional
      attitudes demonstrated strong direct relations with psychological distress. Two
      of the several indices of life stress, total and negative scores on the Life
      Experiences Survey, also correlated with distress. There was no significant
      interaction between the attitude and stress measures. Cognitions, at least on the
      functional-dysfunctional dimension, did not moderate the impact of life events.
      Rather, both attitudes and life stresses were strong independent variables that,
      in additive fashion, provided considerable power for predicting distress.

PMID- 1392218
TI  - Stress effects of personal control over hospital noise.
AB  - Hospital critical care unit (CCU) sounds, instruction in personal control over
      noise, and stress were studied in 105 female volunteers attempting to sleep
      overnight in a simulated hospital environment. Subjects were randomly assigned to
      three groups--instruction in personal control over noise, no instruction in
      personal control over noise, or a quiet condition. The two noise conditions heard
      audiotaped recorded playback of CCU nighttime sounds. The subjects with
      instruction in personal control received directions for using a sound conditioner
      to block out unwanted sounds. This intervention failed to result in less stress.
      The results of group comparisons provided strong support for a causal
      relationship between CCU sounds and greater subjective stress (p less than .000)
      but not for physiological stress measured by urinary epinephrine. As predicted,
      scores for sensitivity of the person to noise were positively correlated with
      scores for noise-induced subjective stress (r = .226, p less than .05).
      Hierarchical multiple regression revealed that CCU sound levels independently
      accounted for 54% (p less than .001) and sensitivity to noise for 5% (p less than
      .01) of the variance in subjective stress.

PMID- 1392219
TI  - How significant are methicillin-resistant Staphylococcus aureus in long term
      geriatric care?

PMID- 1392221
TI  - Characteristics of elderly people taking psychotropic medication.
AB  - A sample of 253 elderly people who had been taking psychotropic medication for at
      least 3 months were interviewed to establish their levels of morbidity and their
      subjective health status. The findings were compared with those of a control
      sample of 484 elderly people in the same area. Those taking psychotropic
      medication were older and more were female and widowed than were the control
      sample. Their subjective assessments of health status were worse as were the more
      objective measures of mental and physical morbidity; in addition they were taking
      more medication of other types. There were more falls among those taking
      psychotropic medication than those who were not; most excess falls took place
      indoors. It is possible that a proportion of this morbidity is a result of or
      exacerbated by medication, but care needs to be taken in interpreting a cross
      sectional study. Older people, we suggest, may benefit from regular review of the
      need for psychotropic medication. Larger studies need to be initiated to
      investigate the association between morbidity and psychotropic medication.

PMID- 1392220
TI  - Felodipine. A review of the pharmacology and therapeutic use of the extended
      release formulation in older patients.
AB  - Felodipine is a dihydropyridine calcium antagonist which may be administered once
      daily in an extended release (ER) formulation. As monotherapy in older patients
      with mild to moderate essential hypertension, felodipine ER once daily provides
      effective control of blood pressure (BP). The drug has also been effective,
      either as monotherapy or in combination with other antihypertensive medications,
      in comparisons with other antihypertensive agents, and does not adversely affect
      lipid profiles or, in patients with diabetes mellitus, glycaemic control. Results
      in patients with angina pectoris and congestive heart failure indicate a
      potential role for felodipine ER in these indications and data also suggest the
      drug reduces left ventricular hypertrophy. In addition, felodipine ER appears
      suitable for use in patients with concomitant respiratory disease, renal or
      hepatic dysfunction, cerebrovascular or peripheral ischaemic disease, or gout,
      making it particularly useful in the elderly who often have more than one
      significant clinical condition. Felodipine ER has generally been well tolerated
      by older patients in clinical trials, although further confirmation in the long
      term is desirable. Thus, felodipine ER effectively lowers BP in older patients
      with essential hypertension with the added convenience of once daily
      administration. It may be used as monotherapy or in combination with other
      antihypertensive agents and is a practical advance in the treatment of
      hypertension in the elderly.

PMID- 1392222
TI  - Special considerations required for the formulation and administration of total
      parenteral nutrition therapy in the elderly patient.
AB  - Providing total parenteral nutrition (TPN) to hospitalised patients is not a
      benign procedure and can be associated with appreciable risks including the
      development of septic, mechanical and/or metabolic complications. In the older
      patient, the risks are heightened due to the effects of aging on vital organ
      function, as well as on the body's ability to respond to injury and infection. In
      addition, the existence of co-morbid disease will increase the rate of
      complications. The design of nutritional regimens must account for the changes in
      body composition and function with age in order to reduce the risks of nutrition
      related complications. As a consequence of the reduction in lean body mass and
      organ function, coupled with the need to mobilise endogenous protein during acute
      metabolic stress, it is prudent to provide protein intakes of 1.5 g/kg/day,
      similar to amounts given to younger adult populations. In contrast, the caloric
      intake should be reduced by as much as 30% from amounts given younger adults of
      equivalent height and weight in order to avoid the dangers of overfeeding. Single
      fuel systems may be better choices in those with acute cardiovascular disease, as
      glucose is a preferred fuel in this setting, whereas a mixed-fuel system will
      generally allow improved glucose homeostasis in the diabetic patient. Once TPN is
      instituted, metabolic management may be as important as nutritional support.
      Critical illness is associated with a variety of electrolyte disorders which are
      often accentuated by concurrent drug therapy and pre-existing co-morbid disease.
      The older patient is often less able to withstand abrupt changes in metabolic
      homeostasis. These points underscore the importance of the careful application of
      TPN therapy in the older patient.

PMID- 1392223
TI  - Changes in renal function with aging. Implications for treatment.
AB  - The most important clinical renal function to monitor with aging is the
      glomerular filtration rate (creatinine clearance). Most decisions on drug dosage
      can be based on this information alone as other (tubular) functions of the kidney
      decrease at rates paralleling the decrease in glomerular filtration rate. As
      individuals age, mean creatinine clearances fall at a rate approximating 1% per
      year and there is an increasing variance in creatinine clearances making it
      increasingly important to adjust drug dosages for changes in renal function.
      Since muscle mass and urinary creatinine excretions decrease at nearly the same
      rate, mean serum creatinine concentrations stay nearly constant. One must be
      aware of this phenomenon when using serum creatinine concentrations alone to
      determine drug dosages and intervals.

PMID- 1392226
TI  - Technical improvements in the repair of acute postinfarction ventricular septal
      rupture.
AB  - Postinfarction ventricular septal rupture (VSR) is a high-risk complication
      following myocardial infarction (MI). Surgical treatment has evolved to improve
      an otherwise poor prognosis. Certain subsets of patients remain a formidable
      challenge. The presence of cardiogenic shock has consistently been found to have
      the highest risk. Over a 10-year period, our technique of repair has evolved from
      established procedures to one we believe confers superior results. Endocardial
      patching to viable myocardium reinforced with an epicardial patch not only
      corrects the shunt but maintains ventricular geometry and avoids tension on
      friable muscle. We report on a series of nine consecutive patients in cardiogenic
      shock. The operative mortality was 22%, none due to low cardiac output syndrome,
      shunt recurrence, or bleeding. All patients have been followed with
      transesophageal echocardiography at a mean period of 14 months (range 3-31
      months). One patient is in New York Heart Association (NYHA) Class I, four are in
      NYHA Class II, and two in NYHA Class III.

PMID- 1392225
TI  - Adverse effects of antidepressants in the elderly.
AB  - Depression is a common problem in old age and the use of antidepressant drugs is
      particularly prevalent among elderly patients. Limited data suggest that dose
      requirements may be lower in the elderly because of age-related changes in
      pharmacokinetics and perhaps also in sensitivity. The side effect profiles of the
      various antidepressants are reviewed with regard to their potential to cause
      specific problems in the older patients. Anticholinergic actions, orthostatic
      hypotension and sedative effects warrant particular care in the elderly.

PMID- 1392227
TI  - Implantation technique for the HeartMate left ventricular assist device.
AB  - The technique for implanting the HeartMate, an intraabdominally placed, pulsatile
      left ventricular assist device, is described. This device, which has been
      developed for potential use in patients requiring permanent left ventricular
      assistance, is currently undergoing clinical investigation in patients requiring
      temporary support as they await cardiac transplantation. This clinical experience
      has demonstrated device safety and efficacy, even for patients requiring extended
      periods of support.

PMID- 1392224
TI  - Percutaneous absorption and age. Implications for therapy.
AB  - Human skin changes dramatically with increasing age. Morphological,
      physiological, and biochemical changes within the tissue have been investigated
      and documented. Considerable interest in transdermal drug delivery to produce
      systemic effect has occurred in recent years. However, it is not known whether
      the penetration barrier of aged skin changes. Morphological and physiological
      changes in aged skin may affect the percutaneous absorption of compounds and thus
      their potential for localised, as well as systemic, efficacy. This article
      reviews the published literature on skin aging changes from adulthood to old age,
      collates these changes with clinical implications pertinent to the practising
      dermatologist, reviews the existing data supporting a change in the barrier
      function of human skin with increasing age, and comments on the relevance of
      conclusions previous investigators have drawn from their studies.

PMID- 1392228
TI  - Automatic implantable cardioverter defibrillator: surgical approaches for
      implantation.
AB  - Surgical approaches for implantation of the automatic cardioverter defibrillator
      are sternotomy, left thoracotomy, subxiphoid, and subcostal. Although any one of
      these may be combined with insertion of one or more of the electrodes
      transvenously, surgical entry into the chest is required for every
      noninvestigational defibrillator implantation operation. The approaches differ in
      exposure provided for selecting electrode sites and for handling untoward events,
      in amount and location of tissue that must be divided or dissected, and in
      average time required. The operation is an electrical one. Its purpose is to
      obtain reliable rhythm sensing so that defibrillation or cardioversion shocks
      will occur only when necessary, and to obtain low enough defibrillation
      thresholds for shocks of 30 joules or less to have a 10-joule defibrillation
      safety margin. Many of the patients have had previous cardiac operations. They
      usually have low or very low ejection fractions. Intraoperative
      electrophysiological testing with often multiple defibrillation episodes is
      required. The choice of approach varies with the state of the patient, the
      institutional experience, and the surgeon. This article describes technique, and
      the advantages and disadvantages of the four approaches as used by four surgeons
      in four different institutions.

PMID- 1392229
TI  - The internal thoracic artery and its branches after coronary artery anastomoses
      in pediatric patients.
AB  - The internal thoracic artery has been favored because of its superior early and
      late patency for coronary artery bypass grafting (CABG) in pediatric patients. We
      have studied the angiographic changes of the internal thoracic artery and its
      side branches before and after CABG with internal thoracic artery to the left
      anterior descending artery. The internal thoracic artery with remaining thymic or
      pericardial branches was patent but showed enlargement of the branches in the
      early period after the operation, and a postoperative exercise test suggested a
      remaining ischemic lesion in the bypass. Angiogram taken 1 year after CABG
      demonstrated the grown internal thoracic artery with disappearance of most of the
      side branches, which had been enlarged 1 month after the operation. Our findings
      suggest the importance of ligation of the whole proximal internal thoracic artery
      branches to maintain good early and late patency.

PMID- 1392230
TI  - Arterial shunt with pump infusion line for the treatment of chronic thoracic
      aortic aneurysms: the "modified shunt of Gott".
AB  - Dissection of the aneurysm is the most dangerous step during graft replacement of
      the descending thoracic aorta. Sudden hemorrhage may follow wall rupture or
      disruption of major collaterals before the aorta can be clamped. A simple
      modification of the classic Gott is illustrated, which makes the shunt work also
      as a partial bypass if needed, with rapid reinfusion of blood losses. Nineteen of
      25 patients requiring resection of descending aortic aneurysms from 1982 to 1990
      were treated with this method with no mortality.

PMID- 1392231
TI  - Annular enlargement during aortic valve replacement: preliminary results with a
      simplified technique.
AB  - A simplified technique has been used to enlarge the aortic annulus in a series of
      13 patients undergoing aortic valve replacement. The procedure basically consists
      of extending the aortotomy incision into the aortic annulus by dividing the
      commissure between the left and noncoronary sinuses, without involving the
      anterior mitral leaflet. Wide opening of the commissure is obtained and the
      resulting defect is closed, preferably using a patch of bovine pericardium
      sutured to the mitral annulus and aortic wall. This technique is simple,
      reproducible, avoids opening of the left atrium (reducing the potential bleeding
      sites), allows insertion of a prosthesis at least two sizes larger than the
      original annulus, and is also applicable in cases of mitral-aortic valve
      replacement. Our preliminary results are satisfactory and seem to demonstrate
      that in many patients, even in the young age group, more complex procedures are
      often unnecessary when enlargement of the aortic annulus is required.

PMID- 1392232
TI  - Cardiac surgery in patients with human immunodeficiency virus infection:
      indications and results.
AB  - Ten patients with human immunodeficiency virus (HIV) infections underwent cardiac
      surgery using cardiopulmonary bypass. All were in Centers for Disease Control
      (CDC) group II. The cardiac involvement was either urgent or severely symptomatic
      in all cases. One patient died due to acquired immunodeficiency syndrome (AIDS)
      unrelated cause. No complications were encountered in this series. Eight of the
      nine survivors were available for follow-up. Three of these eight patients
      progressed to AIDS (CDC group IV) and subsequently died. Five patients are alive
      and in CDC group II. Prognosis of the HIV infection and the natural history of
      the cardiac disease are the two main elements to be considered whenever cardiac
      surgery is required.

PMID- 1392233
TI  - Early and late phase events following bioprosthetic tricuspid valve replacement.
AB  - From 1961 through 1987, 9,247 patients underwent an intracardiac repair for
      valvular heart disease. Five hundred thirty patients had a procedure that
      included a tricuspid valve operation (6%), with tricuspid valve replacement
      performed in 175 patients (2%), of whom 154 had a bioprosthetic valve implanted
      (1.7%). These 154 patients with a bioprosthetic valve in the tricuspid position
      are the subject of this review. There were 27 males and 127 females. Ages ranged
      from 10 to 75 years. There was tricuspid valve insufficiency in 139 patients
      (90%), and stenosis plus insufficiency in 15 (10%). Carpentier-Edwards prostheses
      were implanted in 83 (54%), Ionescu-Shiley in 55 (35%), Hancock in 12 (8%), and
      Mitroflow in 4 (3%). Concomitant procedures were performed in 146 patients (95%).
      At least one previous operation had been performed in 86 patients (56%).
      Preoperatively, 139 patients were in functional Class III or IV (90%). Hospital
      death occurred in 20 patients (13%). Logistic regression analysis revealed that
      incremental risk factors for hospital death included increasing peripheral edema
      preoperatively (p = 0.04), and use of a Hancock prosthesis in the tricuspid
      position (p = 0.03). All 134 hospital survivors were followed at a mean of 66.01
      months, range 1 to 162 months. There were 70 late deaths (52%). Log-rank test
      indicated that incremental risk factors for late death were: longer cross-clamp
      time at repair (p = 0.0007); higher pulmonary artery systolic pressure
      preoperatively (p = 0.01); earlier date of surgery (p = 0.03); and larger
      tricuspid prosthesis size (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392234
TI  - Evaluation of an absorbable suture for sternal closure in pediatric cardiac
      surgery.
AB  - We conducted a study in a prospective fashion using 1-mm diameter absorbable
      sutures (polydioxanone [PDS]) for sternal closure in 50 consecutive patients,
      ages 5 months to 16 years, weighing 5 to 27 kg. Good wound closure and absence of
      any iatrogenic complications were noted. Potential benefits of this approach
      include disappearance of sequelae of the closure and better bone healing. This
      appears to be a safe alternative to standard sternotomy closure.

PMID- 1392235
TI  - Pericardial complications of cardiac surgery: emphasis on the diagnostic role of
      echocardiography.
AB  - Pericardial effusions are common following cardiac surgery; uncommonly they are
      large in size and may cause tamponade, either in the early or late postoperative
      period. Such effusions causing tamponade may be circumcardiac, but are frequently
      loculated, in which case one or more cardiac chambers is selectively compressed.
      Fortunately, echocardiography is capable of imaging not only the presence,
      location, and size of the pericardial effusion, but also indicating the presence
      of tamponade. Constrictive pericarditis resulting from cardiac surgery is being
      recognized with increasing frequency and has been associated with various
      echocardiographic abnormalities. This review also discusses certain other
      pericardial complications of cardiac surgery including supraventricular
      arrhythmias, chylopericardium, and posttransplant problems.

PMID- 1392236
TI  - Omental transfer for the treatment of mediastinitis in an infant.
AB  - Mediastinitis following congenital heart surgery is relatively uncommon but is
      usually seen in the setting of postoperative low cardiac output. Conservative
      treatment utilizing debridement and irrigation is associated with significant
      morbidity and mortality. We report the successful application of the omental
      transfer technique in the treatment of mediastinitis in a 6 month old.

PMID- 1392237
TI  - Macromastia as a factor in sternal wound dehiscence following cardiac surgery:
      management combining chest wall reconstruction and reduction mammoplasty.
AB  - Major sternal wound infection occurs in nearly 2% of patients following coronary
      artery bypass graft surgery. The relationship of this complication to gender has
      not been reported in detail, nor has female breast size previously been
      implicated as a factor increasing the risk of sternotomy dehiscence. We report
      two cases of sternotomy wound dehiscence in women with large, pendulous breasts
      undergoing myocardial revascularization surgery and postulate that the weight of
      large, unsupported breasts produced inferolateral tension on the midline
      sternotomy incisions, contributing to dehiscence of the wounds. Chest wall
      reconstruction was accomplished using pectoralis muscle flaps, and the procedures
      were combined with amputative reduction of the size of the breasts, with
      subsequently successful healing in each case. Combining sternal reconstruction
      with breast reduction surgery may lead to improved secondary outcome, and
      postoperative use of supportive brassieres may reduce the frequency of this
      complication.

PMID- 1392239
TI  - Future of MR imaging is linked to functional imaging.

PMID- 1392240
TI  - Does MR imaging need the media?

PMID- 1392238
TI  - Severe subaortic stenosis in interrupted aortic arch.

PMID- 1392241
TI  - Dynamic MR imaging of human brain oxygenation during rest and photic stimulation.
AB  - Dynamic FLASH (fast low-angle shot) magnetic resonance (MR) imaging was used to
      monitor changes in brain oxygenation in the human visual cortex during photic
      stimulation. The approach exploits the sensitivity of the gradient-echo signal to
      susceptibility changes induced by varying concentrations of paramagnetic
      deoxyhemoglobin in the cerebral blood pool. After the onset of binocular photic
      stimulation (10 Hz, red light, checker-board), there was a distinct increase in
      the MR signal in the calcarine cortex within 6-9 seconds, indicating a decrease
      in the total deoxyhemoglobin concentration. After the stimulation was switched
      off, the MR signal returned to a basal value within a similar period of time.
      Assuming enhanced blood flow and only a minor increase in oxygen consumption
      (production of deoxyhemoglobin) during physiologic activation, the results
      reflect an enhanced supply of diamagnetic oxyhemoglobin and an increase in the
      partial oxygen pressure in the capillary and venous blood pools. In addition, a
      decrease in the basal MR signal in the calcarine cortex was observed during the
      first 60-90 seconds of persistent activation, which may be understood as an
      autoregulatory adaptation to increased overall brain activity associated with
      information processing due to continuous perception of visual stimuli.

PMID- 1392242
TI  - Identification of aberrant right subclavian artery on MR images of the cervical
      spine.
AB  - Nine cases of aberrant right subclavian artery were identified after review of
      674 magnetic resonance (MR) studies of the cervical spine. This common aortic
      arch anomaly is readily identified on sagittal MR images. All vessels were found
      in the typical retroesophageal location, abutting the esophagus from the
      vertebral C-7 to T-3 levels. Arterial flow created signal voids on T1-weighted
      images and confirmatory increased signal intensity due to flow-related
      enhancement on gradient-echo images. This anomaly should be recognized and
      distinguished from pathologic processes in the prevertebral space. The diagnosis
      may allay patient concern regarding their dysphagia and also have important
      ramifications in certain clinical settings.

PMID- 1392244
TI  - Automated local maximum-intensity projection with three-dimensional vessel
      tracking.
AB  - Despite the simplicity and widespread acceptance of the maximum-intensity
      projection (MIP) technique for displaying three-dimensional (3D) magnetic
      resonance angiographic data, several disadvantages are associated with MIP as it
      is applied to all of the 3D data. These include elevated noise level, reduced
      contrast between small vessels and background tissue, and the inability to
      distinguish arteries from veins. The authors have developed a 3D vessel tracking
      method combined with a local MIP around a given vessel to complement conventional
      MIP and alleviate these problems. The method is referred to as a traveling MIP
      (TMIP). TMIP was evaluated in both patients and healthy volunteers. The results
      indicate that TMIP provides better contrast between vessels and background
      tissue, better lumen definition, and better vascular visualization than either
      MIP or vessel tracking alone.

PMID- 1392243
TI  - Cerebral lactate production and blood flow in acute stroke.
AB  - Eight stroke patients were examined serially in the acute phase and 1 week and 2
      4 weeks after stroke with water-suppressed proton magnetic resonance
      spectroscopy. The time courses of lactate level and regional cerebral blood flow
      were studied. A high lactate level was found in the acute phase. The lactate
      content decreased to barely detectable levels during the following 3 weeks, while
      regional blood flow increased during this period. The inverse relationship
      between lactate level and cerebral blood flow suggests that lactate plays no
      substantial role in the vasodilatation underlying the hyperemia that follows
      reperfusion. The amount of lactate present in the acute phase reflects the
      severity of ischemia in the affected region. The lactate level was still above
      normal in the subacute phase with hyperemia, suggesting lactate production
      through aerobic glycolysis. Thus, the lactate level in the subacute phase
      probably does not reflect the degree of anaerobic glycolysis in hypoxic neuronal
      tissue.

PMID- 1392245
TI  - Effect of hypothyroidism on phosphorus metabolism in muscle and liver: in vivo P
      31 MR spectroscopy study.
AB  - Hypothyroidism is known to affect nearly every organ and organ system of the
      human body. The goal of the present study was to gain insight into the phosphorus
      metabolism and bioenergetic function of striated (calf) muscle and liver in
      patients with hypothyroidism before and after thyroid hormone treatment. With an
      ISIS (image-selected in vivo spectroscopy) magnetic resonance (MR) technique for
      volume selection, phosphorus-31 metabolism of the calf muscle in 10 patients and
      of the liver in seven patients with severe hypothyroidism was studied before and
      after treatment. In addition, spectra from the calf muscle and liver were
      obtained in 10 healthy volunteers. Relative to those from the healthy subjects,
      the P-31 MR spectra from patients with hypothyroidism showed a significantly
      diminished phosphocreatine/inorganic phosphate ratio (P less than .01). After
      thyroid hormone substitution therapy, this ratio returned to normal values within
      several weeks. No statistically significant changes in the spectra of liver
      tissue could be detected. The results support the theory that hypothyroidism
      induces a hormone-dependent, fully reversible impairment of the energy metabolism
      of striated muscle. Changes in liver metabolism observed with biochemical methods
      are apparently not detectable with state-of-the-art P-31 MR spectroscopy.

PMID- 1392246
TI  - Why fat is bright in RARE and fast spin-echo imaging.
AB  - Fast spin-echo (FSE) sequences are becoming popular for T2-weighted clinical
      imaging because they result in a severalfold reduction in imaging time and
      because they provide conventional spin-echo contrast for most tissues. Fat,
      however, has been observed to have anomalously high signal intensity on FSE
      images. The present study shows that the brighter fat results from the multiple
      180 degrees refocusing pulses, which eliminate diffusion-mediated susceptibility
      dephasing and suppress J-coupling modulation of the echo train.

PMID- 1392247
TI  - Practical T2 quantitation for clinical applications.
AB  - Many studies have investigated the use of magnetic resonance relaxation times for
      tissue characterization. A number have been performed in vivo with clinical whole
      body imagers. Unfortunately, the results have yet to establish the role of
      quantitative tissue relaxation time measurements in clinical diagnosis. One of
      the major problems is that the techniques used in many of these studies are error
      prone, making the results inconclusive. In the present study, the problems
      associated with clinical T2 measurements were systematically evaluated in an
      attempt to obtain reliable in vivo quantitation. The authors demonstrate that
      spoiler gradients are the most effective technique for artifact suppression but
      that they render ineffective radio-frequency phase schemes such as the Meiboom
      Gill modification to the Carr-Purcell sequence to compensate experimental
      imperfections. The present study results in a more reliable multi-echo sequence
      for T2 measurement. Preliminary clinical results in brain and cervix demonstrate
      the performance of the new technique.

PMID- 1392248
TI  - Monitoring of laser and freezing-induced ablation in the liver with T1-weighted
      MR imaging.
AB  - During both interstitial laser ablation therapy and cryoablation therapy for
      liver tumors, real-time monitoring is necessary for assessment of ongoing thermal
      effects in tissue. With single-section images obtained every 30 seconds with a T1
      weighted RARE (rapid acquisition with relaxation enhancement) sequence, signal
      intensity changes in both ex vivo and in vivo animal liver were readily seen. The
      reversible loss of signal intensity that took place during laser irradiation and
      the increased intensity at the beginning of cooling can be explained mainly by
      altered T1 due to temperature change. The frozen area was seen as a sudden
      decrease in signal intensity at 0 degrees C due to a T2 decrease. This
      preliminary work showed that the protocol provides enough temporal and
      temperature resolution to accurately depict the extent of thermal damage, as
      confirmed at histologic examination. Signal intensity decreased linearly with
      temperature in the range 10 degrees C-50 degrees C, yielding a pixel-to-pixel
      temperature resolution of 5.37 degrees C.

PMID- 1392249
TI  - Reduced-bandwidth method for F-19 imaging of perflubron.
AB  - A reduced-bandwidth imaging method has been developed to eliminate the chemical
      shift artifacts in magnetic resonance (MR) imaging of the blood substitute
      perflubron (PFB) and simultaneously enhance the signal-to-noise ratio (SNR). The
      two strongest spectral peaks, which have relatively long T2 values (247 and 471
      msec), were used. When the receiver bandwidth is reduced substantially by
      increasing the data acquisition time Ts, the bandwidth across the object becomes
      less than the chemical shift frequency. The reduced bandwidth eliminates
      misregistration by displaying the images corresponding to multiple spectral peaks
      on the same image plane simultaneously. An additional gain due to the reduced
      bandwidth is the reduced thermal Gaussian noise. Unfortunately, the increased Ts
      results in an increased TE, which causes the signal to be attenuated by T2
      relaxation. The optimum measured Ts (and TE) values for successful image
      separation and maximum SNR were 120 and 144 msec for the two spectral peaks,
      respectively. The long TE also suppresses the rest of the downfield spectral peak
      cluster of PFB. The degree of magnetic field inhomogeneity and tissue
      susceptibility across the object may cause some limitations in the application of
      this technique; however, a composite radio-frequency pulse that will allow use of
      additional spectral lines and/or localized volume imaging techniques may be
      incorporated to overcome these limitations.

PMID- 1392251
TI  - Fast, interactive algorithm for segmentation of a series of related images:
      application to volumetric analysis of MR images of the heart.
AB  - Magnetic resonance (MR) cine images of the beating heart have excellent spatial
      and temporal resolution. Extracting the boundaries of the heart from MR images
      for volumetric measurements is of considerable interest; however, since the
      number of images involved is large, tracing the boundaries by hand is tedious and
      prohibitively time consuming. The authors have developed an interactive method of
      boundary detection that uses the correlation between the cardiac boundaries on
      temporally or spatially adjacent images to increase the speed of the process and
      reproducibility of the measurement. A simulated cine MR study of a phantom (total
      of 155 images) and cardiac cine studies of two patients (192 images each) were
      analyzed by two independent observers. Analysis of the phantom data was completed
      in 5.6 minutes (2.16 seconds per image) by observer 1 and 6.3 minutes (2.4
      seconds per image) by observer 2. The percent measurement errors for 31 phantom
      volumes (30-120 mL) were 0.96% and 0.83% for observers 1 and 2, respectively. The
      observers analyzed the patient studies in 14-23 minutes (4.4-7.2 seconds per
      image), with interobserver variabilities of 5.8% and 3.7% for the two patients,
      respectively. The authors conclude that their flexible, semiautomatic,
      interactive algorithm allows rapid and reproducible detection of structural
      boundaries.

PMID- 1392250
TI  - MR imaging of temporomandibular joint abnormalities associated with cervical
      hyperextension/hyperflexion (whiplash) injuries.
AB  - Patients often have temporomandibular joint (TMJ) dysfunction-related symptoms
      after cervical hyperextension/hyperflexion injuries ("whiplash") caused by rear
      end motor-vehicle collisions. To determine abnormalities of the TMJ associated
      with these injuries, 33 consecutive symptomatic patients (66 joints) with no
      direct trauma to the jaw, mouth, head, or face due to the accident and no prior
      history of TMJ dysfunction underwent magnetic resonance (MR) imaging, and the
      images were retrospectively analyzed. Overall, 29 (88%) patients had some type of
      TMJ abnormality related to whiplash injury. Displacement of the disk was seen in
      37 (56%) of the TMJs as follows: 21 (32%) had anterior displacement with
      reduction, nine (14%) had anterior displacement without reduction, six (9%) had
      lateral or medial displacement, and one (2%) had posterior displacement. On T2
      weighted images, 43 (65%) TMJs had abnormal joint fluid or edema, predominantly
      affecting the joint capsule and/or lateral pterygoid muscles. The finding that
      many of the patients had joint fluid and/or soft-tissue edema indicates that T2
      weighted images are especially useful for assessment of patients with a history
      of whiplash injury.

PMID- 1392252
TI  - Minimizing TE in moment-nulled or flow-encoded two- and three-dimensional
      gradient-echo imaging.
AB  - A method for minimizing field-echo delay in moment-nulled gradient-echo imaging
      is presented. Even though ramps are accounted for, the analysis yields simple
      closed-form solutions. The method is then generalized to the section-select
      waveform for three-dimensional volume imaging and to flow encoding for phase
      contrast imaging. Three strategies for first-moment selection in phase-contrast
      imaging are discussed, including a new strategy that always yields the minimum
      echo delay. Trapezoidal and triangular gradient lobe shapes are analyzed.

PMID- 1392253
TI  - Chemical shift artifact along the section-select axis.
AB  - Chemical shift artifact (CSA), familiar to radiologists along the frequency
      encoding axis, also occurs along the section-select axis. The authors observed a
      case in which CSA mimicked a renal mass. Subsequent retrospective analysis of 50
      abdominal magnetic resonance (MR) imaging studies was performed to assess
      occurrence of CSA adjacent to the upper and lower renal poles. CSA along the
      section-select axis was observed in 76% of cases and adjacent to 39% of all renal
      poles imaged. CSA along the section-select axis is common in abdominal MR imaging
      and may occasionally mimic disease.

PMID- 1392255
TI  - Rapid fat/water assessment in knee bone marrow with inner-volume RARE
      spectroscopic imaging.
AB  - An inner-volume modification of a spectroscopic imaging technique based on RARE
      (rapid acquisition with relaxation enhancement) sequences is shown to provide, in
      less than 1 minute, spectra suitable for fat/water peak-area integration from
      selected imaging columns containing more than 1,000 5 x 5 x 1-mm voxels. A
      limitation is the unavoidable T2 weighting of the spectral peaks, which
      influences estimations of true fat/water composition from the spectra. Studies
      obtained in the knees of healthy volunteers demonstrate the ability of the
      technique to enable characterization of the two major proton peaks in bone
      marrow. Data collected at two or more effective TEs are suitable for
      extrapolation of fat/water estimates to zero TE.

PMID- 1392254
TI  - MR imaging of the pericardial cyst.
AB  - Findings obtained with magnetic resonance (MR) imaging in four patients with
      pericardial cyst are reported. MR imaging allowed not only localization and
      diagnosis in all four cases but characterization of cystic content. MR imaging,
      including RARE (rapid acquisition with relaxation enhancement) MR hydrography,
      which shows only liquids with T2s greater than 500 msec, proved to be useful in
      characterizing the fluid content of a mediastinal lesion and monitoring follow
      up. In one case, MR imaging allowed differentiation of a pericardial cyst from a
      suspected necrotic lymph node in a patient with colic carcinoma, with subsequent
      correction of staging and therapy. The authors conclude that MR imaging is the
      method of choice for diagnosis (especially in unusual locations) and monitoring
      of pericardial cysts and for differential diagnosis of malignant mediastinal
      cystic tumors that show a solid part.

PMID- 1392256
TI  - Computer-controlled flow simulator for MR flow studies.
AB  - A novel computer-controlled flow simulator for use in magnetic resonance (MR)
      flow experiments was evaluated. The accuracy in constant-flow mode was better
      than 1%. The accuracy in pulsatile-flow mode was found to be dependent on the
      interconnecting tubing. The short-term and long-term reproducibilities of
      pulsatile waveforms were less than or equal to 0.4 mL/sec (1 standard deviation).
      Increased response times due to the lengths of tubing required in MR flow
      experiments were surmounted by using a modified tubing configuration and
      precompensated waveforms. Piston reversal was found not to cause major
      difficulties in MR flow experiments.

PMID- 1392259
TI  - Do current regimes of hormone replacement therapy protect against subsequent
      fractures?
AB  - It is now accepted that unopposed oestrogen therapy reduces osteoporotic
      fractures by about 50%. Although current regimes with added progestogens are
      thought to act similarly to unopposed oestrogens, no study has yet demonstrated
      an effect on fractures with the former. Using a retrospective cohort design we
      studied fracture rates in women attending a menopause clinic for hormone
      replacement therapy (HRT) and compared them with women derived from the general
      population. Data were analysed from 1075 women exposed to HRT and 1741 non
      exposed postmenopausal women. In all 226 fractures were reported between 1977 and
      1986, the commonest site being the distal radius, occurring in 28 of the HRT
      women and in 37 of the non-exposed women. The incidence density rate for fracture
      of the distal radius is 3.5/1000 woman-years (wy) in non-exposed women. This was
      similar to the rate in the HRT women prior to HRT use, the rate falling by 30%
      after exposure from 3.2 to 2.2/1000 wy. The protective effect on osteoporotic
      fractures increased progressively with duration of use. After 5 years of use the
      relative risk fell to 0.5 (95% confidence interval, 0.2-1.2) for all osteoporotic
      fractures and for the distal radius to 0.18 (95% confidence interval, 0.05-1.3).
      No similar changes were seen for non-osteoporotic fractures. There were 6
      (0.6/1000 wy) reported fractures of the hip in the non-exposed group compared
      with none in the HRT group (when 1.7 were expected based on non-exposed rates) (p
      = 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392260
TI  - Acronyms in bone densitometry.

PMID- 1392258
TI  - Spinal fractures during fluoride therapy for osteoporosis: relationship to spinal
      bone density.
AB  - Recent studies report that fluoride therapy for osteoporosis increases spinal
      bone density without improving vertebral fracture rate, challenging the notion
      that restoration of bone mass improves bone fragility. To further evaluate this
      issue, the relationship between spinal bone density and vertebral fracture rate
      was examined in a large number of fluoride-treated, osteoporotic patients. A
      retrospective assessment was made of clinical data collected from our
      observations of 389 osteoporotics treated with fluoride 30 +/- 8 mg/day (mean +/-
      SD) (equivalent to 66 +/- 17 mg NaF/day) and calcium 1500 mg/day for 28 +/- 18
      months. Fracture rate and bone density were assessed in the same region of the
      spine (i.e., T12 through L4) using quantitative computed tomography (QCT). Spinal
      bone density increased with time on fluoride, but the relationship was hyperbolic
      (r = 0.99, p less than 0.0001; asymptote = 167 mg/cc on double-reciprocal plot),
      suggesting a plateau in the response. The spinal fracture rate decreased as a
      function of time on therapy (r = -0.83, p less than 0.01), and was inversely
      related to spinal bone density during fluoride therapy (r = 0.70, p less than
      0.001 on arithmetic plot; r = -0.79, p less than 0.001 on semi-log plot). The
      subgroup of patients who responded to treatment with a significant increase in
      spinal bone density had a 48% reduction in spinal fracture rate compared with non
      responders (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392261
TI  - Women with climacteric symptoms: a target group for prevention of rapid bone loss
      and osteoporosis.
AB  - The relations of vasomotor symptoms to the rate of bone loss and to the response
      of forearm bone mineral density (BMD) to hormone replacement therapy (HRT) were
      analyzed in a 2-year non-randomized study. Forty peri/postmenopausal women who
      were given HRT for climacteric symptoms were compared with untreated control
      women, individually matched for age and length of time since the last menstrual
      period. The women who received HRT gained, on average, about 2% in BMD, while the
      control women lost about 6% (mean group difference 8%; 95% confidence interval
      (CI) 5.7-10.2). Adjustment for potential confounders did not change the results.
      Sweating frequency was inversely correlated with serum estradiol levels (p =
      0.05). Among untreated women the rate of bone loss was higher in those who had
      frequent sweating initially than in those with less frequent sweating (9% vs. 4%,
      mean difference 4.3%; 95% CI 0.7-7.8, p = 0.023). Among women who received HRT,
      those who had the highest frequency of sweating initially, compared with those
      with a lower frequency, showed a greater gain in bone density (mean difference
      4%; 95% CI 1.2-6.8, p = 0.007). In multivariate analysis adjusting for
      covariates, sweating frequency remained an independent determinant of change in
      bone density in women both with and without HRT. When sweating frequency and
      serum estradiol levels were compared in a multivariate analysis, only sweating
      frequency showed an independent association with rate of bone loss. The findings
      indicate that women with severe climacteric symptoms may have an excessive rate
      of bone loss and should therefore be considered as a special target group for
      prevention of osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392262
TI  - Are calcium intakes and physical activity patterns during adolescence related to
      radial bone mass of white college-age females?
AB  - The determinants of bone mass, i.e., size and density, in young adult women after
      cessation of growth in length of the bones are not well understood. Usual dietary
      calcium (Ca) intakes and physical activity (PA) patterns during the post-pubertal
      half-decade have been considered as two important factors contributing to bone
      mass. In the present hypothesis-generating cross-sectional study, radial bone
      mineral content and density were measured by single-photon absorptiometry at two
      sites containing different proportions of trabecular and cortical bone tissue in
      705 healthy, Caucasian college women (18-22 years). Ca intake during high school
      and college, as estimated by milk and cheese intake only, was categorized into
      low, moderate and high groups; and physical activity, estimated during the same
      time frame, was also categorized into low, moderate and high groups. Bone
      measurements were related to both long-term dietary Ca intake from milk and
      cheese and long-term PA in sports, dance or other exercises, as assessed by
      recall. By univariate analyses, both distal and mid-radial bone mineral content
      (BMC) and areal bone mineral density (BMD) were found to be positively related to
      gynecological age (GA) (p less than 0.01). Also, independent effects of long-term
      Ca intake (p less than 0.05) on distal BMC and BMD, and of long-term PA (p less
      than 0.05) on distal and mid-BMC and BMD were observed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1392263
TI  - No secular increase in the prevalence of vertebral fractures due to
      postmenopausal osteoporosis.
AB  - We examined whether the prevalence of vertebral fractures in otherwise healthy,
      70-year-old Danish women had increased during an interval of 10 years. The
      population-based epidemiological study included two age-matched groups of
      postmenopausal women. Group 1 consisted of 70-year-old women (n = 386) living in
      a defined area of suburban Copenhagen recruited in 1979 for an epidemiological
      study. Of the 285 women who were entered, 173 were judged healthy, without
      secondary causes of osteoporosis. Group 2 was recruited by sending questionnaires
      to all women aged 68-72 years living in the same area in 1989. Of the 512 women
      who attended a medical screening, 387 were found to be without secondary causes
      of osteoporosis and had a spinal radiograph. Radiographs of the thoracolumbar
      spine were assessed for vertebral fracture by five radiological methods. There
      was no significant difference between the two groups in the prevalence of
      vertebral fractures and the 95% confidence intervals overlapped completely in all
      methods. The prevalence rates varied by method from about 35% to more than 80%
      but the distribution of fracture types was similar in the two groups. We conclude
      that the prevalence of vertebral fractures due to postmenopausal osteoporosis has
      not increased since 1979 in otherwise healthy women residing in suburban
      Copenhagen, and that comparison of prevalences between studies requires that they
      use the same method of radiological assessment.

PMID- 1392265
TI  - Cardioprotective effect of estrogen.

PMID- 1392264
TI  - Measurements of broadband ultrasonic attenuation in the calcaneus in
      premenopausal and postmenopausal women.
AB  - We report a study of broadband ultrasonic attenuation (BUA) in the calcaneus in
      248 women. Measurements were performed with a Walker-Sonix UBA-575 ultrasonic
      bone analyser. The populations studied were 15 healthy young volunteers (group 1,
      mean age 26 years), 200 healthy pre- and postmenopausal women (group 2, mean age
      53 years) and 33 osteoporotic women with vertebral crush fractures (group 3, mean
      age 66 years). Subjects in group 1 each had 10 repeated measurements of their
      right heel. Duplicate BUA measurements in the right heel were performed in 96
      subjects and bilateral scans in a further 87 women in group 2. The remaining 17
      subjects in group 2 and those in group 3 had a single scan of the right heel. All
      women in groups 2 and 3 had dual X-ray absorptiometry (DXA) scans of the lumbar
      spine and femoral neck. The precision study on the women in group 1 gave a root
      mean square (RMS) coefficient of variation (CV) of 4.2%. Individual CV results
      showed statistically significant differences (range 1.3%-7.6%). Duplicate scans
      in subjects in group 2 gave a RMS CV of 4.6% while the bilateral measurements
      showed no significant difference between the two heels. Linear regression
      analysis gave the following relationship between BUA and age: BUA = 87.1 - 0.76
      (Age - 40) dB/MHz (r = -0.31, p less than 0.001, SEE = 14.0 dB/MHz). Multivariate
      regression analysis showed that, in addition to age, years since the menopause
      was also a significant factor in predicting BUA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392266
TI  - A screening and counseling program for prevention of osteoporosis.
AB  - Prevention of osteoporosis is an increasingly salient public health concern as
      our society ages. This report describes the procedures used at an osteoporosis
      center to which people come for screening and counseling. The patients on whom
      this report is based were 53 non-smoking women, 1-10 years postmenopausal at the
      time of their first visit to the center, who chose not to undertake estrogen
      therapy, and who returned for a second visit in 12-18 months. They were
      classified as to adequacy of calcium intake (at least 750 mg/day) and exercise
      (at least 3 h/week of weight-bearing exercise) at both visits; complete data on
      calcium intake and exercise were available on 46 of the women. Bone densities
      were measured at the femoral neck and lumbar spine with dual energy X-ray
      absorptiometry, and at the distal radius with single photon absorptiometry. At
      the first visit, 67% of the women reported adequate exercise and 43% reported
      adequate calcium intake. At the second visit, the percentages in the adequate
      categories had increased to 74% for exercise (p = 0.06) and 70% for calcium
      intake (p = 0.02). Age at the first visit was inversely correlated with femoral
      (r = -0.40, p = 0.003) and spinal (r = -0.36, p = 0.009) bone densities; the
      correlation with radial bone density did not achieve significance (r = -0.27, p =
      0.55). Rather than declining, as would be expected in early postmenopausal women,
      bone density rose slightly, but not significantly, between visits for all three
      sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392269
TI  - [Responsibilities and goals of hospital hygiene].

PMID- 1392268
TI  - Bone mineral content in women: trends of change.
AB  - Altogether 426 women had their forearm bone mineral content (BMC) measured with
      single photon absorptiometry (SPA): one group in the early 1970s, another about
      18 years later. Both groups represented purportedly healthy subjects. A third
      group of 328 women, measured at the same time as the second group, was from the
      same population but chosen by random selection (the population-based group). In
      the two sets of non-population-based women there was a small percentage reduction
      in the cortical forearm bone mass in the recent measurement as compared with the
      earlier measurement. This was significant only in women below 70 years of age.
      The forearm BMC, both cortical and trabecular, was less in all age groups of
      women randomly selected from the same population as the healthy control sample.
      This difference emphasizes the importance of selecting normative data from a
      population-based sample.

PMID- 1392267
TI  - Risk of osteoporosis in men with chronic bronchitis.
AB  - Theoretically, patients with chronic bronchitis are at risk for osteoporosis.
      Bone metabolism was assessed in 44 male chronic bronchitics treated with oral
      prednisolone (C+; n = 19) or with bronchodilatory drugs alone (C-; n = 25). In
      both groups, serum osteocalcin was lower (p less than 0.001) than in age- and sex
      matched controls (mean (ng/ml) C+ 1.0, C- 1.9, controls 4.2), while testosterone
      was at the lower limit of the reference range. Low trabecular bone mineral
      density (BMD) was noted in the C- group (median Z score -1.0), but both cortical
      and trabecular BMD were depressed in the C+ group (-1.0 and -1.4, respectively).
      In conclusion, chronic bronchitics treated with corticosteroids, even at low
      doses, are at risk for osteoporosis. In both groups, additional factors such as
      hypogonadism might be responsible for low BMD and low osteocalcin levels. A
      decrease in bone formation is a possible mechanism of action.

PMID- 1392270
TI  - [Status of the guideline for hospital hygiene and prevention of infection of the
      Federal Public Health Office].
AB  - 1976 the Federal health Office published the guideline "Erkennung, Verhutung und
      Bekampfung von Krankenhausinfektionen". The guideline defines the levels of
      hospital hygiene and gives important directions to physicians and nursing staff.
      The guideline has been increasingly incorporated in regulations.

PMID- 1392271
TI  - [Refuse disposal in the hospital].
AB  - From the point of view of hygiene and the prevention of infection, waste products
      from hospitals have to be divided into three groups: household type refuse,
      refuse specific to hospitals, refuse from infectious wards. Particular care has
      to be taken in hospitals with the collection and transport of specific hospital
      refuse and refuse from infectious wards, but after being delivered to the central
      collecting point the former--in contrast to refuse from infectious wards--can be
      removed together with household type refuse in the normal manner by the local
      waste disposal service. If it is not to be incinerated, refuse from infectious
      wards may only be disposed to together with household type refuse after
      undergoing a good disinfection practice.

PMID- 1392272
TI  - [Functional construction aspects of surgical units].
AB  - The historical development of Hospital hygiene is described showing in particular
      the demands made on the construction of operating units deduced from this
      evolution. Modes of infection inside operating units are considered and possible
      measures to interrupt these are discussed. The fundamental ideas expressed in the
      first version of the annex "Operating Unit" to the guidelines of the Federal
      Public Health Office "On the Identification, Prevention and Control of Hospital
      Infections" are explained in detail. The demands formulated originally are
      examined critically and the 1990 version is discussed. In addition, update
      requests are put forward such as ambulatory operation and new operating methods
      such as minimal-invasive operating, as well as new hygienic hazards arising from
      the increase of equipment inside operating theatres. An additional section deals
      with the fundamental ideas of DIN 1946, part 4, as far as operating units are
      concerned.

PMID- 1392273
TI  - [Hospital kitchens].

PMID- 1392274
TI  - [Perspectives of the hospital hygiene team].
AB  - Since 1976, the training of hygiene experts exists in the Federal Republic of
      Germany. At the same time, the functions were formulated in the General
      Directions for Hospital Hygiene and Prevention of Infections of the Federal
      Public Health Office, Berlin. Meanwhile, there are records and statistics which
      show that hygiene experts are not only staff of documentation of the hospital
      hygiene, but realize diverse specialized and responsible functions. In June 1991,
      VHD carried out an opinion research poll in 600 German hospitals (= 17.1% of the
      hospitals in the FRG) the situation of the hygiene experts. Due to these results,
      a very representative statement is possible on the functions and work of hygiene
      experts in hospitals. Because of an improved and longer training of hygiene
      experts, which has been in force since January 1st, 1992, the preparation of
      installing more training centres is important, in order to the demand qualified
      hygiene experts.

PMID- 1392275
TI  - [Update of DIN 19.643--treatment and disinfection of swimming pool and bathing
      tub water].
AB  - German Standards Specification DIN 19,643 is at present under revision for health
      reasons and because of both negative and positive experiences gathered in
      practice. To enable adaptation of the standards specification to future
      developments, a Part I of the specification is being created comprising the
      demands to be made on the quality of the water and general demands on the
      construction and operation of swimming pools and tubs and basins in bath houses,
      e.g. in spas or municipal swimming pools. The subsequent parts of the new
      specification (Part 2 to Part n) concern the demands to be made on individual
      combinations of processes; these can be supplemented at any time in accordance
      with technical progress without requiring revision of the entire standards
      specification. Essential innovations are the reformulation of the required
      efficiency of disinfection, the introduction of the parameters Legionella
      pneumophila, trihalogen methane (THM) and the reduction of the limit value for
      chloramines. Technically speaking, the new features concern the automatic
      measurement of the auxiliary parameters of hygiene such as redox potential, pH
      value and free chlorine, automatic control of disinfectant additions, automatic
      filter rinsing with fluidization of the filter-bed to a prescribed minimum bed
      expansion, and the sight-glas at the filter container. The demands made on
      Jacuzzi and warm water spouted bed besins are integrated into the specification,
      thus obviating the need for German Standards Specification DIN 19,644.

PMID- 1392276
TI  - [Examination and evaluation of the hygiene status of natural peloids for human
      medical use].
AB  - For curative treatment in German spas, different muds for medical mud-baths and
      mud-packs are also used besides mineral springs. Muds of this kind are known by
      the collective term of "peloids". According to the "Definitions of the German
      Health Resorts Association", peloids are classified by a new geological-genetic
      system. After discussing hygienic aspects and problems of diverse therapeutic
      applications using peat, marine muds or fango, standardized methods for
      microbiological examinations are described. For the microbiological control
      parameters E. coli, Coliform organisms, Staphylococcus aureus, Pseudomonas
      aeruginosa and Candida albicans, suggested values and threshold values are given
      in detail.

PMID- 1392277
TI  - [Draft of the swimming pool water regulation. Presentation, status: 17 September
      1991, according to the federal hearing of 11 December 1991 in Bonn].
AB  - Comments are given on the present status of regulations concerning water in
      swimming pools and baths--1991--(in connection with the KOK regulations--1972-
      and the Federal German standard [DIN] No. 19643-1984-). Reference is made to
      microbiologic limits of Legionella pneumophila among others.

PMID- 1392278
TI  - [Construction hygiene in the area of bathing and recreation].
AB  - Construction hygiene in the bathing and recreation areas underwent many changes
      during the decades. In each case it was accomplished very intensively and defined
      by the actual needs of the population or by those responsible for the population.
      With regard to the development of bathing since the Romans, the bathing habits of
      the Roman times, during the Middle Ages, at the 18th century, at the beginning of
      the 19th century and of today are characterized broadly. The respective
      constructional as well as the hygienic measures are also shown and discussed in
      this context. Whereas the Roman thermals created prerequisites for physical
      activity as well as possibilities for spare time, and in the early Middle Ages,
      sexual excesses and the risk factors connected thereby led to the transfer of
      infectious diseases and consequently to the elimination of the public baths. At
      the beginning of the 18th century first the cleaning of the body and at the
      beginning of the 20th century physical activity became very important. With the
      help of the construction plans for baths and shower-baths and swimming pools of
      1906 the aims and purposes of the baths are discussed and the respective
      constructional changes are shown the example of warm water baths (swimming pools)
      in Hamburg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392279
TI  - [Public health requirements in physical therapy].
AB  - Physiotherapy involves manifold measures that are partly not clearly separated
      from other methods of therapy. In most cases the skin or mucosa are not injured
      so that the danger of infectious complications is relatively low. On the other
      hand, patients with severe underlying diseases which are problematic from the
      aspect of hygiene in connection with infections, may have to be treated (for
      example, intensive-care patients, patients with decubital ulcers etc.) In such
      patients physiotherapy must comply with hygienic precautions that are employed
      with other diseases and treatments to prevent the transfer of pathogens. Special
      rules govern the composition of the water and the servicing of equipment used in
      hydrotherapy (German DIN standard specification No. 1964). Guidelines for the
      water used in municipal swimming pools and baths are in preparation. Other rules
      to be observed concern the recognition, treatment and prevention of nosocomial
      infections. In addition, every establishment must set up definite rules for
      regular measures to prevent infections and to monitor these measures, especially
      with regard to cleaning and disinfecting.

PMID- 1392280
TI  - [Sanitation measures in evidence of Legionella].
AB  - Appearance of Legionella disease generally is underrated. Conclusions as to
      disease frequency from Legionella antibody investigations are not reliable. The
      number of microbes necessary to produce illness depends from individual
      preliminary conditions. In special areas of the hospital the rate of diseases
      caused by Legionella can be reduced by protection. In bathing areas generally the
      hitherto existing regulations of the Federal Health Authority are sufficient:
      Continual warm water temperature increases from 60 degrees C, chlorination if
      necessary, regular stepwise controls. Insufficient results are produced by
      intermittent temperature increases. Filters that are impermeable for microbes
      appear uneconomical for bathing areas.

PMID- 1392281
TI  - Atrazine, alachlor, and carbofuran contamination of well water in central Maine.

PMID- 1392282
TI  - Screening test of the biodegradative capability of a new strain of Pseudomonas
      gladioli (BSU 45124) on some xenobiotic organics.

PMID- 1392283
TI  - Characterization of methomyl dissipation on grape foliage.

PMID- 1392284
TI  - Adsorption characteristics of trichloroethylene and 1,1,1-trichloroethane onto
      activated carbon fiber in gaseous phase.

PMID- 1392285
TI  - Effect of three newer pesticides on microbial and enzymatic activities in soil.

PMID- 1392286
TI  - Persistence of chlordane applied to an intertidal sandflat.

PMID- 1392288
TI  - Behavioral reactions of fishes exposed to unbleached kraft mill effluent.

PMID- 1392287
TI  - Different pathways for the uptake of benzo(a)pyrene adsorbed to sediment by the
      mussel Mytilus galloprovincialis.

PMID- 1392289
TI  - Acute toxicity of cadmium to two species of infaunal marine amphipods (tube
      dwelling and burrowing) from New Zealand.

PMID- 1392290
TI  - Heavy metal and hydrocarbon residues in tissue and blood of beef steers bedded on
      waste newspapers.

PMID- 1392291
TI  - Lead contamination around a kindergarten near a battery recycling plant.

PMID- 1392292
TI  - Mining area environmental mercury assessment using Abies alba.

PMID- 1392293
TI  - Biological monitoring of workers exposed to mevinphos in greenhouses.

PMID- 1392294
TI  - Elevated cholinesterase activity and increased urinary excretion of inorganic
      fluorides in the workers producing fluorine-containing plastic
      (polytetrafluoroethylene).

PMID- 1392295
TI  - Preliminary evaluation of nonwoven chemically treated barrier fabrics for field
      testing of protective clothing for agricultural workers exposed to pesticides.

PMID- 1392296
TI  - Cancer risk assessment for the inhalation of 1,3-butadiene using physiologically
      based pharmacokinetic modeling.

PMID- 1392298
TI  - Changes in fatty acid composition of rat serum induced by a free radical
      generator.

PMID- 1392300
TI  - Preliminary evaluation of metal contamination of soils from the Gulf War
      activities.

PMID- 1392299
TI  - Malathion induced changes in the serum proteins and hematological parameters of
      an Indian catfish Heteropneustes fossilis (Bloch).

PMID- 1392297
TI  - Differential therapeutic responses of thiol compounds in the reversal of
      methylmercury inhibited acid phosphatase and cathepsin E in the central nervous
      system of rat.

PMID- 1392301
TI  - Lead contamination and mobility in surface water at trap and skeet ranges.

PMID- 1392302
TI  - Optimized design for earthworm survival tests in soil.

PMID- 1392303
TI  - Evaluation of toxi-chromotest direct sediment toxicity testing procedure and
      microtox solid-phase testing procedure.

PMID- 1392304
TI  - Mosquito coils: a source of elemental pollution.

PMID- 1392305
TI  - Contamination of air samples by alkanes from Parafilm.

PMID- 1392306
TI  - Cadmium accumulation in the mummichog, Fundulus heteroclitus, adapted to various
      salinities.

PMID- 1392307
TI  - Influence of cadmium on PCB congener accumulation in quail.

PMID- 1392309
TI  - Potential health risk via inhalation/ingestion exposure to polychlorinated
      dibenzo-p-dioxins and dibenzofurans.

PMID- 1392308
TI  - Simple colorimetric method for the assessment of aniline exposure--analysis of
      urinary p-aminophenol.

PMID- 1392310
TI  - Calculated reentry interval for table grape harvesters working in California
      vineyards treated with methomyl.

PMID- 1392311
TI  - Critical gestational day of teratogenesis by di-n-butyltin diacetate in rats.

PMID- 1392312
TI  - Changes in erythropoietic activity of Sarotherodon mossambicus exposed to
      sublethal concentrations of the herbicide diuron.

PMID- 1392313
TI  - Role of cyanobacteria in the removal of lignin from the paper mill waste waters.

PMID- 1392314
TI  - Production of antibacterial substances by macroalgae of the New York/New Jersey
      coast, USA.

PMID- 1392315
TI  - Effect of the herbicide diquat on the growth of microalgae and cyanobacteria.

PMID- 1392316
TI  - Comparative accumulation efficiency of 109cadmium from natural food (Hyalella
      azteca) and artificial diet by rainbow trout (Oncorhynchus mykiss).

PMID- 1392317
TI  - Application of the short-term chronic test with Ceriodaphnia dubia in identifying
      sources of toxicity in industrial wastewaters.

PMID- 1392318
TI  - Effect of sodium sulfite on the mutagenicity of chlorinated drinking water.

PMID- 1392319
TI  - Toxic effects of pollutants on methane production in sediments of the River
      Rhine.

PMID- 1392320
TI  - Immunologically induced coronary artery stenosis in allografts after heart and
      heart-lung transplantation in rats.
AB  - The role of the lung in suppressing immunologically induced coronary artery
      stenosis after heterotopic allograft transplantation was studied in rats. Thirty
      nine recipients were divided into two groups: untreated and treated. The
      untreated group was divided into two subgroups--the heart allograft TH group and
      the heart-lung allograft THL group. The treated group was divided further into
      four subgroups depending on when the graft was harvested, after 30 days or 60
      days (T30-H and T30-HL group, and T60-H, T60-HL, respectively). Rejection was
      assessed by Lurie's classification. The percent of intraluminal stenosis (PIS)
      was determined by planimetry. All treated animals received cyclosporin A 10
      mg/kg/day intramuscularly for 20 days. In the untreated group, heart-lung
      allograft survival was longer than heart allograft survival. In the treated
      group, all grafts were still beating when the animals were killed. The rejection
      grade score in the T30-H and T30-HL groups were lower than those in the T60-H or
      T60-HL groups. The PIS in the THL group was slightly lower than that in the TH
      group. However the PIS increased over time in both the TH and THL groups. This
      study demonstrates that the lung suppresses but does not abolish immunologically
      induced coronary atherosclerosis-like occlusive lesions after cardiac
      transplantation.

PMID- 1392321
TI  - Estimated weight of the residual parathyroid gland after parathyroidectomy using
      plasma levels of the parathyroid hormone.
AB  - The possibility of estimating the total weight of the parathyroid glands based on
      the plasma concentration of the parathyroid hormone (PTH) would be of great help
      when searching for the parathyroid glands during surgery on patients with
      secondary hyperparathyroidism. Thus, we studied the relationship between the
      levels of carboxyl-terminal PTH (C-PTH), midportion PTH (M-PTH) and intact PTH,
      and the weight of the parathyroid glands resected for secondary
      hyperparathyroidism. The subjects studied were 11 patients with secondary
      hyperparathyroidism caused by chronic renal failure. The pre- and post-operative
      differences in the plasma C-PTH levels and plasma M-PTH levels were significantly
      correlated with the weight of the resected parathyroid glands (p less than 0.001
      for both), but there was no correlation between the differences in the levels of
      intact PTH and the weight of the resected parathyroid glands. From these
      relationships we estimated the weight of the residual parathyroid gland after
      parathyroidectomy using the levels of each PTH. All patients in whom the residual
      parathyroid gland was estimated to be heavy based on the levels of M-PTH showed
      recurrence of hyperparathyroidism after the parathyroidectomy. We therefore found
      that estimation of the weight of the parathyroid glands from the levels of M-PTH
      is both possible and useful.

PMID- 1392257
TI  - Comparative map for mice and humans.

PMID- 1392322
TI  - Marked and prolonged depression of factor XIII after esophageal resection.
AB  - Anastomotic leakage is one of the most common complications of esophagectomy and,
      since Factor XIII is required for normal wound healing, we investigated the
      temporal changes in plasma Factor XIII following esophagectomy and hepatectomy. A
      control group of patients undergoing other abdominal operations was also studied.
      Factor XIII activity was determined before surgery and on postoperative days
      (POD) 1, 3, 7 and 14. The plasma levels of acute phase protein were also
      measured. The plasma Factor XIII activity decreased significantly in both the
      hepatectomy and control groups until POD 7, reaching the lowest level on POD 3.
      In contrast, the esophagectomy group showed significant decreases in Factor XIII
      levels throughout the postoperative study period, with a nadir with an average
      activity of 56 per cent on POD 7. Preoperative transferrin levels had a positive
      correlation with Factor XIII levels measured on POD 3 and there was also a
      positive significant correlation between Factor XIII activity and alpha 2
      macroglobulin levels on POD 3. These results suggest that there is a marked and
      prolonged depression of plasma Factor XIII activity following esophagectomy which
      may be attributed to accelerated tissue demands, inadequate synthesis or
      increased degradation. Moreover, the severe and sustained decrease in Factor XIII
      activity may be related to poor wound healing after esophagectomy.

PMID- 1392323
TI  - A clinical study of postoperative infections following open-heart surgery:
      occurrence and microbiological findings in 782 cases.
AB  - A total 782 consecutive patients underwent open-heart surgery with CPB between
      January, 1979 and December, 1988, at the Yamagata University Hospital. We
      assessed the incidence of postoperative infections in relation to age, the
      duration of surgery and antibiotic prophylaxis, and examined the causative
      organisms, after which the types of infecting flora were compared between the 1st
      period, from 1979 to 1983 and the 2nd period, from 1984 to 1988. Postoperative
      infection occurred in 104 of the 782 patients (13.3 per cent); in the form of a
      wound infection in 41 (5.2 per cent), pneumonia in 33 (4.2 per cent), urinary
      tract infection in 9 (1.2 per cent), prosthetic valve endocarditis in 6 (0.8 per
      cent), and other infections in 15 (1.9 per cent). Patients aged under 12 months
      or over 60 years showed a higher incidence of infection, being 17.4 per cent and
      19.2 per cent, respectively. Patients who underwent an operation of over 8 hours
      duration also had a significantly higher incidence compared to those whose
      operation time was less than 4 hours, being 32.9 per cent and 6.3 per cent,
      respectively (p less than 0.0001). There was no significant difference in the
      incidence of postoperative infection between patients given or not given
      preoperative prophylaxis. A total 123 species of organisms were isolated from the
      104 patients, 52.8 per cent being gram-negative bacteria (GNB), and 43.9 per cent
      gram-positive bacteria (GPB), and a remarkable increase in the incidence of GPB
      was seen in the 2nd period compared to the 1st period from 31.7 per cent to 50.0
      per cent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392326
TI  - Hemodynamic changes after resection of thoracic duct for en bloc resection of
      esophageal cancer.
AB  - An en bloc resection of esophageal cancer is one of the most radical forms of
      esophagectomy, and includes the resection of the thoracic duct, but a relatively
      high hospital mortality rate has been reported. There is very little knowledge on
      the pathophysiological changes after resection of the thoracic duct. We examined
      24 patients who underwent en bloc resection. Some patients developed severe
      tachycardia or shock postoperatively which subsided after a massive infusion of
      plasma. Analysis of the fluid balance revealed that much more fluid was necessary
      during surgery and the postoperative 24 h than in patients treated by a standard
      esophagectomy. Postoperative lymphangiography or CT revealed abnormal collateral
      lymphatics around the kidneys or in the pelvic cavity. This suggests the
      development of the lymphaticovenous shunts, which differed depending on the
      anatomy of each patient. One patient with chronic hepatitis developed
      uncontrollable ascites. These are important findings which can hopefully reduce
      the high rate of hospital death after this operation.

PMID- 1392324
TI  - The relationship between lymph node metastases and DNA-ploidy status as
      prognostic factors in invasive breast cancer.
AB  - We evaluated the relationship between the regional lymph node metastases and the
      DNA ploidy status in 207 patients with invasive breast cancer, as well as their
      prognostic values in estimating the prognosis of breast cancer. A significantly
      higher incidence of aneuploidy was found in patients with a large T3 or T4 tumor,
      a positive axillary lymph node status, more than 4 positive axillary lymph nodes
      or positive internal mammary lymph nodes. In a univariate study, the overall
      survival was significantly correlated with tumor size, axillary lymph node
      status, axillary and internal mammary lymph node metastases, and DNA ploidy
      status. In the multivariate analysis, however, only axillary and internal mammary
      lymph node metastases were recognized as important independent prognostic factors
      on survival. In this series, the DNA ploidy status did not appear to be an
      independent prognostic factor either in the entire series or in negative axillary
      node patients, since it was closely correlated with the axillary or internal
      mammary lymph node metastases, and the axillary node negative patients had an
      extremely favorable prognosis.

PMID- 1392325
TI  - The antitumor activity and immunosuppressive effects of 5-fluorouracil
      suppositories in rectal cancer patients.
AB  - The antitumor activity and immunological effects of the local administration of
      5FU were investigated by determining the tissue concentration of 5FU,
      histological appearance of the primary tumor, and lymphocyte subsets of the
      regional lymph nodes in 23 rectal cancer patients. Twelve patients were treated
      with 5FU suppositories preoperatively, being the 5FU group, while 11 patients
      were given no preoperative treatment, being the control group. The 5FU
      concentrations in the primary tumors were higher than those in the regional lymph
      nodes and appeared to remain high for an extended period. No histological changes
      peculiar to the 5FU group were observed in the primary tumors. An analysis of the
      lymphocyte subsets in the pararectal nodes revealed that Leu2a+15- cells, or
      cytotoxic T lymphocytes, were significantly decreased in numbers in the 5FU group
      compared to the control group. These results suggest that the local use of 5FU
      may not only exert an antitumor effect against rectal cancer, but can also cause
      the suppression of antitumor immunity in the regional lymph nodes.

PMID- 1392328
TI  - A correlation between arterial ketone body ratio and concentration of beta
      hydroxybutyrate as an indicator of hepatic functional reserve.
AB  - We have investigated the correlation between the arterial blood ketone body ratio
      (AKBR) and beta-hydroxybutyric acid (HBAC) in the course of a 75 g glucose
      tolerance test. The correlation was revealed to be represented by an equation of
      Y = A + BX [X = log(HBAC), Y = log(AKBR)] with high significance. This expression
      existed in both normal individuals and patients with liver, biliary tract or
      pancreas disease. The postoperative course was unsatisfactory because of liver
      dysfunction in cases whose value B was more than -0.6 in bisegmentectomy and more
      than -0.45 in uni- or subsegmentectomy. The coefficient B in the equation was
      suggested to contribute to the evaluation of hepatic functional reserve.

PMID- 1392327
TI  - Polymorphonuclear leukocyte function and serum opsonic activity in surgical
      patients.
AB  - Thirty-six patients who underwent major surgery were studied in order to clarify
      the perioperative changes in polymorpho - nuclear leukocyte (PMNL) function and
      serum opsonic activity. In patients without postoperative infection, the PMNL
      phagocytic-bactericidal capacity and plasma elastase levels significantly
      increased, while the serum opsonic index remarkably decreased just after surgery,
      however, all returned to the preoperative levels within 1 or 2 weeks. Conversely,
      in patients with postoperative infection, the PMNL bactericidal capacity and
      plasma elastase levels remained at high levels even after 1 or 2 weeks, while the
      PMNL phagocytic capacity and serum opsonic index substantially decreased after 2
      weeks compared with the patients without postoperative infection. Plasma
      leukotriene B4, which is a potent chemo-attractant for PMNL, noticeably decreased
      in the patients with postoperative infection on the first postoperative day
      compared with that in the patients without postoperative infection. Our data
      suggests that the most important predisposing factors to postoperative infection
      may be a depressed PMNL phagocytic capacity and a lower serum opsonic activity
      after surgery, and that the increased PMNL bactericidal capacity and high plasma
      elastase levels during postoperative infection may contribute to the
      susceptibility to multiple organ failure.

PMID- 1392329
TI  - Factors contributing to deficiencies in cell-mediated immunity in esophageal
      cancer patients.
AB  - Based on the previous data which indicated a preoperative decrease in cell
      mediated immunity (CMI) is associated with the occurrence of infectious
      complications following surgery on patients with esophageal cancer, we examined
      possible factors contributing to a decrease in CMI levels. A multiple linear
      regression analysis was made on data from 76 patients with esophageal cancer and
      53 with gastric cancer as the control. In patients with esophageal cancer, both
      protein-calorie malnutrition (PCM) and age factor contributed to a decrease in
      CMI, although the contribution of the latter was weak while the stage of the
      cancer and the grade of dysphagia showed no such contribution. The PCM and stage
      of the cancer were contributing factors in patients with gastric cancer. Thus,
      these results indicate that PCM and old age, and not the presence of malignant
      tumors, play a significant role in deficiency in CMI in patients with esophageal
      cancer.

PMID- 1392331
TI  - Aggressive repeat liver resection for hepatic metastases of colorectal carcinoma.
AB  - Although hepatectomy for liver metastases from colorectal carcinoma is an
      effective treatment, recurrence in the liver is still the most common site after
      hepatectomy. Thirty patients underwent hepatectomy for hepatic metastases and 17
      of them had recurrence in the remnant liver during the following 12-year period.
      Six of the 17 patients underwent a removal of isolated hepatic recurrences. Two
      of the six patients underwent a third hepatectomy, and three patients underwent
      partial lung resection on a total of five occasions. There were no operative
      deaths while complications after a third hepatectomy contributed to a high
      morbidity rate of 40 per cent. The mean length of survival of the six patients
      was 28.5 months from the second hepatectomy. The prognosis of the six patients
      who underwent a repeat hepatectomy was significantly better than that of patients
      with unresectable recurrence after an initial hepatectomy (p less than 0.01). The
      overall 5-year survival of 29 patients excluding one in-hospital death was 44.7
      per cent. Our results reveal that aggressive removal of isolated and resectable
      recurrent disease has the potential to improve the prognosis of selected patients
      with metastatic cancer.

PMID- 1392330
TI  - Effect of intra-hepatoarterial infusion of MMC and CDDP for gastric cancer
      patients with liver metastases.
AB  - The influence of operative treatment and chemotherapy on the prognosis in 93
      gastric cancer patients with liver metastasis was studied. Chemotherapy included
      the systemic administration of mitomycin C (MMC) (39 patients), an intra
      hepatoarterial infusion of MMC (MMC IAC group) (19 patients) and an intra
      hepatoarterial infusion of MMC and cisplatin (CDDP) (MMC + CDDP IAC group) (24
      patients). Either MMC or MMC and CDDP were given in 1-4 courses every 3-4 weeks
      from the first one to two post operative weeks. The response rate was 4 per cent
      (1/23), 29 per cent (5/17) and 73 per cent (17/23) for MMC systemic
      administration, MMC IAC and MMC + CDDP IAC, respectively, with a significantly
      high rate of effectiveness for the MMC + CDDP IAC. In addition, regarding the
      median survival period, the MMC + CDDP IAC group showed 11.8 months, as compared
      with 2.9 months for other chemotherapeutic treatments, indicating a good
      prognosis regardless of any possible resection of the primary lesion. A Cox
      proportional hazard model revealed the treatment by MMC + CDDP IAC alone to be a
      significant independent factor. These results indicated that MMC + CDDP intra
      arterial chemotherapy is an effective approach to gastric cancer with liver
      metastasis.

PMID- 1392333
TI  - Retrograde jejunogastric intussusception: is endoscopic or surgical management
      more appropriate?
AB  - Jejunogastric intussusception (JGI) is a rare complication which can develop
      after partial gastrectomy, gastroenteroanastomosis or enteroanastomosis. Although
      its management is usually surgical, an endoscopic reduction can alternatively be
      attempted. We present herein a case of acute JGI in which failure of endoscopic
      reduction required surgical resection and reconstruction. This is followed by a
      discussion based on the current available literature.

PMID- 1392332
TI  - A case of multiple leiomyomatous lesions of the lung: an analysis of flow
      cytometry and hormone receptors.
AB  - A 36 year old woman was admitted to our department because of a chest X-ray which
      showed multiple developing shadows. She underwent bilateral exploratory
      thoracotomies and a total 5 tumors were resected and pathologically diagnosed as
      benign metastasizing leiomyoma, the largest of which was positive for the
      progesterone receptor and negative for the estrogen receptor. A histogram of this
      tumor using a flow cytometer showed a diploid pattern and 4.6 percent of the S
      phase which was not more than that of a leiomyoma of the uterus from another
      patient. Two months later, she underwent a hysterectomy and bilateral salpingo
      oophorectomy for treatment of the positive progesterone receptor in the pulmonary
      lesions. The resected uterine myoma and normal myometrium showed positive
      estrogen and progesterone receptors. For the subsequent 28 months she has been
      free of any further symptoms. Benign metastasizing leiomyoma of the uterus is a
      rare disease and very interesting because of its histological benignity and
      hormonal dependency. However, according to the literature, it is often confused
      in entity due to the fact that normal lung tissue also possesses hormone
      receptors. Considering our data on hormone receptors, it is rational to think
      that multiple leiomyomatous lesions in the lung should only be diagnosed as
      benign metastasizing leiomyomas when they possess positive estrogen and
      progesterone receptors.

PMID- 1392335
TI  - Anomalous arrangement of the pancreaticobiliary ductal system without dilatation
      of the biliary tract.
AB  - A rare case of anomalous arrangement of the pancreaticobiliary ductal system
      without dilatation of the biliary tract (AAPBDS without DBT) associated with
      mucosal dysplasia of the biliary duct is described herein. A 53 year old male
      with a long history of diarrhea and right upper abdominal pain was diagnosed as
      having AAPBDS without DBT by endoscopic retrograde cholangiopancreatography and
      other examinations. Excision of the gallbladder and biliary duct with a Roux-en-Y
      hepatico-jejunostomy was performed and subsequent pathological examination of the
      surgical specimens showed mucosal hyperplasia of the gall-bladder and mucosal
      dysplasia of the biliary duct. Considering the dysplastic changes of the biliary
      duct as seen in our case, and the high incidence of AAPBDS without DBT developing
      into carcinoma of the biliary duct, being 12.2 per cent, we suggest that
      pancreaticobiliary ductal diversion with excision of the gallbladder and biliary
      duct should also be performed for AAPBDS without DBT. However, further
      pathological investigations concerning the excised biliary duct in AAPBDS without
      DBT will be need to be carried out.

PMID- 1392334
TI  - A rare cause of digestive hemorrhage: an aneurysm of the superior
      pancreaticoduodenal artery rupturing into the duodenal stump of a Billroth II
      partial gastrectomy.
AB  - We report herein a case of an iatrogenic superior pancreaticoduodenal arterial
      aneurysm which ruptured into the duodenal stump of a Billroth II partial
      gastrectomy. Superselective angiography was used for the diagnosis, and
      successful embolization performed nonoperatively. A review of the literature
      revealed both the etiology and site of rupture in this case to be extremely
      uncommon.

PMID- 1392337
TI  - What is general surgery: definition, education and practice.

PMID- 1392336
TI  - A case of localized peritonitis caused by obstructive colitis proximal to rectal
      carcinoma: a rare manifestation of obstructive colitis.
AB  - A case of obstructive colitis associated with rectal carcinoma in a 56 year old
      Japanese man is reported herein. He presented to Shinkokura Hospital with severe
      abdominal pain following a one month history of anal bleeding and mild abdominal
      pain. On palpation, muscle guarding was observed in the left lower quadrant and
      the white blood cell count was 14,200/mm3. An exploratory laparotomy was
      performed under the provisional diagnosis of acute abdomen, which revealed
      localized peritonitis 8 cm oral to an area of rectal carcinoma. An anterior
      resection of the lesion was therefore performed together with a descendo
      proctostomy. The histopathologic diagnosis revealed adenocarcinoma and
      obstructive colitis involving the entire thickness of the sigmoid colon and
      resultant fibrino-purulent peritonitis. His post-operative course was uneventful
      and he was continuing to do well on the 30th postoperative day, at the time of
      writing. The clinical significance of this combination of obstructive colitis
      with rectal carcinoma is briefly discussed following the presentation of this
      case.

PMID- 1392338
TI  - Living related liver transplantation.
AB  - Liver transplantation from a brain death donor has not yet been accepted in
      Japan. The only alternative method at present is transplantation from a living
      donor. After the first successful living related liver transplantation was
      performed by Strong in Brisbane, Australia, Japanese hepatic and transplant
      surgeons also began to perform such operations. As of February 1991, 16 living
      related liver transplantations had already been performed in Japan, mainly for
      children with biliary atresia. Five of these patients subsequently died, however,
      our patient has survived more than 1 year, and she is presently leading a normal
      school life. The most important issue regarding living related liver
      transplantation is to ensure the donor's safety. For this purpose, we conducted a
      preoperative banking of the donor's own blood and plasma. In addition, a
      selective vascular occlusion was carried out to reduce blood loss during the
      resection of the liver. Intraoperative color Doppler ultrasonography was
      introduced for evaluating the circulation of the graft. By using this modality,
      the following three points were able to be accurately estimated in order to
      obtain optimal graft perfusion: 1) The most suitable position for the graft to be
      fixed to the abdominal wall, 2) whether or not the abdominal wall could be closed
      and 3) the indication for a ligation of the collateral veins to form a porto
      systemic shunt. Thanks to these procedures, living related liver transplantations
      have now become an acceptable transplant method, however, a transplantation from
      a cadaver that is brain dead but still has a beating heart is still absolutely
      necessary for adult recipients. Therefore, in the future, both methods should be
      performed.

PMID- 1392339
TI  - Coronary artery bypass grafting in patients with depressed left ventricular
      function: operative results and long-term follow-up.
AB  - Nine consecutive patients with coronary artery disease who had a left ventricular
      ejection fraction (LVEF) of less than 0.4 and underwent coronary artery bypass
      grafting (CABG) at our institution were studied. All patients had angina pectoris
      and six of the nine patients (67%) had a history of congestive heart failure. The
      mean EF was 0.37 +/- 0.03 and the mean LV end-diastolic pressure was 10.1 +/- 4.9
      mmHg. An average of 1.56 +/- 0.50 grafts per patient were placed and there was no
      operative death. The graft patency rate was 92.9% and the mean EF rose
      significantly from 0.37 to 0.53 after surgery (P less than 0.05). There was one
      late death, the 4-year actuarial survival rate being 88.9%. Of the eight long
      term survivors, six (75%) were totally asymptomatic and only two had mild angina
      on exertion. This study confirmed that CABG for patients with depressed LV
      dysfunction can be performed safely with an acceptably low operative mortality, a
      significant improvement of LV function, and excellent long-term results.

PMID- 1392340
TI  - Endocrine neoplasms of the pancreas: a clinicopathologic study of 24 cases and
      immunohistochemical remarks.
AB  - A total of 24 patients with endocrine neoplasms of the pancreas were
      clinicopathologically and immunohistochemically studied. They consisted of 18
      patients with adenoma and 6 with carcinoma. Of the 24 patients, 13 developed
      attacks of hypoglycemia due to hyperinsulinemia, and 1 developed an
      uncontrollable duodenal ulcer caused by the hypersecretion of gastrin, however,
      the remaining 10 were asymptomatic. No prediction could be made as to the site of
      origin of the tumors. A clear difference was seen between adenoma and carcinoma
      in the size of the mass, the mean greatest diameter of the 18 adenoma cases being
      1.7 cm, while that of the 6 carcinoma cases was 7.3 cm. One of the 13 insulinomas
      and a gastrinoma was malignant, while all 24 tumors were positive for neuron
      specific enolase. The 13 insulinomas were diffusely positive for insulin and 5
      were also shown to be focally immunoreactive for gastrin, with 3 also being
      immunoreactive for somatostatin and 2 for pancreatic polypeptide. The gastrinoma
      showed immunoreactivity for somatostatin, insulin, pancreatic polypeptide, and
      glucagon in addition to a positivity to gastrin. The above findings thus indicate
      the multiple hormone synthesis of endocrine neoplasms of the pancreas.

PMID- 1392342
TI  - Ultrasonic exploration of contralateral side in pediatric patients with inguinal
      hernia.
AB  - The width of low echoic region at the internal ring (WLIR) of an inguinal canal
      demonstrated by ultrasonography was applied in the preoperative diagnosis of the
      contralateral side in pediatric patients with inguinal hernia. The ultrasonic
      diagnosis of 39 pediatric patients with inguinal hernia and 38 children without
      inguinal hernia under 15 years of age were conducted at Hamamatsu University
      Hospital from April 1988 to January 1989. The WLIR of children without inguinal
      hernia were within 6 mm in boys under 15 years of age and within 3 mm in girls
      under 5 years of age. There were no statistically significant differences between
      the WLIR of the right side and that of the left side, and the WLIR of the
      following three age groups also demonstrated no statistical significance: under 1
      year of age, 1 to 5 years of age, 5 to 15 years of age. On the other hand, the
      WLIR of the hernia side of pediatric patients with inguinal hernia were
      significantly wider than that of the contralateral side in boys and girls under 5
      years of age (P less than 0.01), as well as in boys 5 to 15 years of age (P less
      than 0.05). Therefore, we recommend a contralateral exploration for pediatric
      patients with inguinal hernia when the WLIR is 7 mm or more in boys under 15
      years of age and 4 mm or more in girls under 5 years of age.

PMID- 1392341
TI  - Low anterior resection versus abdominoperineal excision: a comparison of local
      recurrence after curative surgery for "very low" rectal cancer.
AB  - In the controversy regarding whether sphincter-saving resection (SSR) or
      abdominoperineal resection (APER) is more appropriate for the treatment of very
      low rectal cancer, local recurrence rates seem to play a fundamental role in
      patient outcome. In order to operate an effective patient selection, very low
      rectal cancer is defined herein as being located within 4.5 to 7.5 cm from the
      anal verge. This retrospective report investigates the incidence of local
      recurrence after curative surgery for very low rectal carcinoma in 24 consecutive
      patients treated by the same surgical team over a 15-year period using the above
      surgical procedures. In the APER group, the local recurrence rate was 45.5%,
      occurring in 5 of 11 cases; and in the SSR group 46.1%, occurring in 6 of 13
      cases, with no significant difference between the two groups. Recurrence was
      found within one year of surgical treatment in all except one case. Despite the
      strict follow-up program, it was only possible to perform reoperation in two
      recurrent cases, both previously submitted to SSR and diagnosed by means of
      transanal ultrasonography and macrobiopsy. The high incidence of local recurrence
      in this series is explained by the advanced stage of disease in the majority of
      cases. Thus, as the choice between APER and SSR does not seem to affect the
      incidence of local recurrence, which is related more to tumor size, site, stage,
      and grading, preservation of the sphincters and restoration of digestive
      continuity should be achieved whenever technically possible.

PMID- 1392343
TI  - The increase of low density subpopulations and CD10 (CALLA) negative neutrophils
      in severely infected patients.
AB  - We investigated the changes in polymorphonuclear leukocyte (PMN) subpopulations
      that accompany severe bacterial infection and examined their usefulness as a
      parameter for assessing the severity of infection. The Percoll density gradient
      was used to fractionate neutrophils into subpopulations of high density (1.09
      1.10), intermediate density (1.08-1.09), and low density (1.07-1.08) with the
      majority of neutrophils from normal volunteers being of high density. By
      contrast, neutrophils from infected patients were of intermediate or low density,
      while those from severely infected patients showed a high percentage of the low
      density fraction with functional changes in lower chemotactic and beta
      gulcuronidase activity. When each density subpopulation in the normal blood
      neutrophils was tested, low density PMNs had the lowest chemotaxis and minimal
      beta-glucuronidase activity. These results indicate that the increase in low
      density PMNs in patients with severe infection clearly reflects the functional
      impairment of PMNs. Flow cytometric analysis demonstrated that the neutrophils
      from severely infected patients had an decrease in CD10 expression. The
      percentage of CD10 positive PMNs correlated well with the severity of infection
      and with the clinical course of the patients. Thus, we conclude that PMN-density
      and CD10 expression change during severe bacterial infection, and that the
      measurement of PMN-subpopulations may be used to complement the clinical
      assessment of the severity of infections.

PMID- 1392344
TI  - Initial hepatic metabolic function in canine liver and pancreas cluster
      transplantation.
AB  - In this study, initial hepatic metabolic function was evaluated by determining
      the arterial ketone body ratio (AKBR) and plasma amino acid concentrations in an
      experimental orthotopic combined hepatopancreatic transplantation (OHPT), and
      comparing the same values in orthotopic liver transplantation (OLT). In OHPT,
      AKBR decreased in the anhepatic phase and recovered to the preoperative value
      just 1 h after reperfusion. On the other hand, in OLT, the recovery of AKBR took
      3 h after reperfusion with a significant difference compared to OHPT (P less than
      0.05). Plasma amino acid levels, especially alanine and total free plasma amino
      acids increased in the anhepatic phase and recovered within 1 h of reperfusion in
      OHPT. However, they did not recover until 3 h after reperfusion in OLT. This
      rapid recovery of hepatic metabolic function in OHPT should be attributed to the
      order of reperfusion in which the reconstruction of arterial blood flow precedes
      that of portal blood flow. This model is useful for assessing the best way by
      which the grafted liver can for assessing the best way by which the grafted liver
      can control the timing, order, rate, and volume of blood that should be released.

PMID- 1392346
TI  - The postoperative recurrence of Crohn's disease: an analysis of 37 patients with
      Crohn's disease who underwent endoscopy during initial surgery.
AB  - A total 37 patients with Crohn's disease who underwent intraoperative endoscopy
      during resection of the affected intestine were evaluated in this study. The
      average age of the patients at surgery was 23.2 years. The residual lesions in
      the remaining intestine identified by intraoperative endoscopy were classified
      according to their pathologic profiles into three groups: A, B and C. In group A,
      comprising patients with longitudinal ulcers and/or a cobblestone appearance, 10
      of 12 patients had recurrence. In 5 of these 10, the residual lesions were
      exacerbated and 2 required a further operation. The remaining 5 patients showed
      recurrence at the site of previous anastomosis and 2 of these 5 required
      additional surgery. In group B, comprising patients with small ulcers, aphthoid
      ulcers, or scars, and group C, comprising patients with no residual lesions,
      recurrence was observed in 13 of 16, and 3 of 9 patients, respectively. The
      recurrent lesions were all found proximal to, or at the site of previous
      anastomosis. Additional operations were performed on 3 of the group B patients.
      The findings of this study revealed that recurrence requiring additional surgery
      is more frequent at the site of anastomosis, regardless of the endoscopic
      appearance of the residual lesions.

PMID- 1392345
TI  - The hemostatic effect of deacetylated chitin membrane on peritoneal injury in
      rabbit model.
AB  - In this study, we determined the effect of 80% deacetylated chitin (DAC-80)
      membrane on postsurgical bleeding after visceral and parietal peritoneal
      abrasion. Japanese white rabbits underwent a midline laparotomy followed either
      by a bilateral peritoneal sidewall abrasion (4 x 4 cm) or an abrasion of liver
      surface (3 x 2 cm). The injured surface was then covered with a 0.2 mm thick DAC
      80 membrane. On postsurgical day 2, the rabbits were sacrificed and the amounts
      of postsurgical bleeding was determined by quantitating the number of red blood
      cells recovered in 50 ml peritoneal lavage fluid. The DAC-80 membrane was found
      to reduce postsurgical bleeding after the abrasion of liver surface (treated with
      DAC-80 membrane: 2.9 +/- 0.8; control: 24.6 +/- 5.9 x 10(8) cells/peritoneal
      cavity, P less than 0.005). This same hemostatic activity was not observed after
      application in the peritoneal sidewall abrasion model. We also measured
      plasminogen activator activity (PA) and urokinase inhibitory (PAI) activity in
      the spent culture media of macrophages recovered from the postsurgical peritoneal
      exudate. The DAC-80 membrane reduced the PA secretion from postsurgical
      macrophages after liver surface abrasion (treated with DAC-80: 2.8 +/- 0.7;
      control: 3.9 +/- 0.9 mPU/ml). The DAC-80 membrane also showed similar effects on
      PA secretion after peritoneal sidewall abrasion. No significant effects were
      found in the secretion of PAI by postsurgical macrophages in both surgical
      models. These findings suggest that the DAC-80 membrane may have hemostatic
      activity through the modulation of fibrinolytic activity of peritoneal exudative
      macrophages.

PMID- 1392347
TI  - Lymphangioma in the small intestine: report of a case and review of the Japanese
      literature.
AB  - We report herein a rare case of a 53 year old man with a benign lymphangioma of
      the small intestine. He presented with a complete obstruction of the small
      intestine and radiological examination revealed a small intestinal tumor. A long
      intestinal tube was passed, the intestinograms from which detected a submucosal
      tumor of the small intestine. Partial resection of the small intestine was thus
      performed and the tumor was found to be located mainly in the submucosa. The
      final pathological diagnosis was made as cavernous lymphangioma. This case is
      presented with a description of the roentgen appearance, followed by a review of
      the Japanese literature.

PMID- 1392348
TI  - Adenoma of the nipple.
AB  - We report herein a case of a 42 year old woman with adenoma of the nipple of her
      left breast. The diseased nipple was enlarged, reddened and a hard elastic mass
      was palpable within its substance. There was an area of eczematoid erosion on the
      surface. Incisional biopsy revealed a picture of adenoma and therefore the nipple
      was excised. Five years postoperatively, there has been no recurrence of the
      disease. To our knowledge, only thirteen cases of adenoma of the nipple have been
      reported in the Japanese literature. Some clinical features and treatments are
      discussed in a review following the case report. Although rare, adenoma of the
      nipple should be borne in mind to avoid a misdiagnosis of malignancy and
      unnecessarily extensive surgery.

PMID- 1392349
TI  - Primary malignant lymphoma of the spleen.
AB  - We treated two patients with primary splenic malignant lymphoma. One was a 63
      year-old man with diffuse histiocytic non-Hodgkin's lymphoma accompanied by
      multiple liver metastases which were composed of necrotic tissue probably due to
      preoperative transarterial chemoembolization (TAE). He eventually died of liver
      failure two years and six months after splenectomy. The autopsy revealed that a
      large part of the cirrhotic liver had been occupied by a diffuse-type
      hepatocellular carcinoma, but no recurrence of the malignant lymphoma was found
      in the liver or other organs. The second patient was a 40-year-old woman with a
      massive invasion of the stomach, colon, pancreas, and diaphragm by a splenic
      tumor. The splenic tumor and the adjacent involved organs were resected.
      Pathologically, well-differentiated diffuse lymphocytic non-Hodgkin's malignant
      lymphoma was evident. No recurrence has been found for six years and two months.
      Based on an evaluation of the 71 patients with primary splenic malignant lymphoma
      reported to data in Japan, the patients treated by a curative resection in an
      early clinical stage have a more favorable prognosis.

PMID- 1392350
TI  - A perforated non-specific ulcer of the cecum as seen in a 2-year-old female.
AB  - A 2-year-old female was hospitalized because of generalized peritonitis with
      pneumoperitoneum. A laparotomy disclosed a perforated ulcer of the cecum. A
      resection of the perforated portion of the cecum was then performed.
      Histopathologic examinations confirmed that the ulcer was non-specific in nature.
      No recurrence was observed four years since the limited operation.
      Pneumoperitoneum caused by perforation of non-specific cecal ulcer in a child
      has, to our limited knowledge, not yet been previously reported.

PMID- 1392351
TI  - Pilonidal sinus on the neck.
AB  - A recurrent nuchal abscess was treated in a 21-year-old obese young man with a
      total excision of the lesion. In the histopathological findings, many
      similarities were found between this lesion and pilonidal sinus. We discuss the
      pathogenesis of this lesion, as well as our belief that this case was a rare
      example of pilonidal sinus on the neck.

PMID- 1392352
TI  - A scintigraphic analysis of colonic movement in patients with colostomy: changes
      of colonic transit time after acquaintance with irrigation.
AB  - For the purpose of making a functional assessment of colostomy irrigation, eight
      patients were examined. Group A was composed of four patients whose experience of
      irrigation was less than one year. Group B was composed of four patients who had
      undergone irrigation for more than two years. The capacity of the remnant colon
      was determined by a barium enema. Next, 74 MBq of milking technetium 99
      diethylene triamine penta-acetic acid (99mTc-DTPA) was instilled with a
      predetermined amount of water (37 degrees C). A dynamic scan was performed for 45
      min. The mean evacuation time of Groups A and B were 6 min 56 s +/- 2 min 33 s
      and 13 min 27 s +/- 10 min 50 s, respectively. The mean half emptying time of
      Groups A and B were 142.5 s +/- 7.9 s and 309.0 s +/- 181.9 s. The results
      suggest that the remnant colon may be habituated with irrigation. Colostomy
      irrigation which uses a single instillation of a measured volume of tepid water
      is recommended.

PMID- 1392353
TI  - Nursing's new professional paradigm.

PMID- 1392354
TI  - Reference values for radial bone width and mineral content using single photon
      absorptiometry in healthy children aged 4 to 10 years.
AB  - Bone width and mineral content were measured in 420 healthy Cambridge children
      aged 4 to 10 years using single photon absorptiometry. The results are expressed
      first in the form of standard centile charts, with additional prediction charts
      which provide body-size-adjusted estimates for the measurements, and
      interpretation centiles for comparing these estimates with the actual
      measurements. The values obtained are similar to those reported for American
      children aged five to six years after adjusting for body-size differences. We
      suggest that appropriate application of these prediction charts will facilitate
      the use of single photon absorptiometry in monitoring and treating children who
      have disorders of bone growth and mineralization.

PMID- 1392355
TI  - Human milk components cross-reacting with antibodies against bovine beta
      lactoglobulin.
AB  - The human whey components cross-reacting with antibodies raised against bovine
      and/or equine beta-lactoglobulin were screened systematically. The milk of six
      women on a normal diet was collected within 72 h of confinement and whey
      components were fractionated by high-speed size exclusion chromatography and
      reversed-phase techniques. The fractions which were immunoreactive in double
      diffusion experiments with antisera anti-bovine and/or equine beta-lactoglobulin
      were subsequently purified by native PAGE and then electroblotted on Pro-blott
      membrane (Western blotting). Pro-blot membranes were stained in parallel with
      Coomassie and by immunostaining using antibodies against bovine and/or equine
      beta-lactoglobulin as first antibody solution. The immunoreactive bands were cut
      out from the membrane and N-terminally sequenced; all the immunoreactive
      components were clearly identified as human beta-casein or its (mainly tryptic)
      fragments. The strong antigenic similarity between human beta-casein and beta
      lactoglobulin (bovine and equine) might be of immunological importance; it could
      mean that breast-fed neonates risk being sensitized to beta-lactoglobulin
      irrespective of the presence of cow's milk in the mother's diet.

PMID- 1392356
TI  - Supplementation of an adapted formula with bovine lactoferrin. 2. Effects on
      serum iron, ferritin and zinc levels.
AB  - Breast milk provides an excellent supply of most nutrients for newborn infants.
      Infant formulae should be nutritionally comparable to breast milk especially with
      regard to critical nutrients like iron and other trace elements. Infant formulae
      supplemented with various amounts of bovine lactoferrin were given to two groups
      of infants. These infants were compared with infants receiving unsupplemented
      formula and breast-fed infants. The effects of these diets on levels of
      haemoglobin, haematocrit, serum iron, ferritin and zinc were examined for a study
      period of 150 days. At birth, concentrations of iron, haemoglobin, haematocrit
      and zinc were comparable in all four feeding groups. The fact that the serum zinc
      level was not altered by lactoferrin supplementation appears to rule out an in
      vivo effect of lactoferrin on zinc nutrition of infants. Ferritin levels of
      breast-fed infants were significantly higher than in non-supplemented formula-fed
      infants at day 30 and day 90. This difference was seen only at day 30, when
      comparing breast-fed infants to lactoferrin-supplemented formula-fed infants.
      Comparing the infants receiving formulae, the formula supplemented with the
      higher amount of bovine lactoferrin induced significantly higher serum ferritin
      levels compared to the unsupplemented formula at day 90 and day 150. These
      observations favour the idea that lactoferrin may be involved in iron absorption.
      Since this effect was pronounced only after 90 days, it has to be discussed as to
      whether this effect is a convincing argument for supplementing infant formulae
      with bovine lactoferrin.

PMID- 1392357
TI  - Breast feeding and the dietary habits of children in rural Somalia.
AB  - Breast feeding and dietary habits were studied prospectively in a cohort of
      children under the age of five years in a rural Somali community. The median
      duration of breast feeding was 19.5 months. However, all the children also
      received cow's milk by cup from the first day of life and onwards. Energy
      supplements (mainly sugar and oil) as well as additional water were given daily
      from early infancy. Staples, protein-rich foods (beans and meat), vegetables and
      fruits were usually introduced when the children reached the age of 12-18 months.
      There was a seasonal variation with the lowest intake of protein-rich and vitamin
      rich foods during the rains in May to June. Thus, there was a complete absence of
      exclusive breast feeding. Energy-reinforced cow's milk and human milk dominated
      the diet up to the age of one year. Staples were mixed with oil and supplemented
      with milk, thereby leading to a much higher energy density in the complementary
      food than is usually the case in African communities.

PMID- 1392358
TI  - Risk factors for early termination of breast feeding in Brazil.
AB  - A prospective study was undertaken to identify possible factors related to the
      duration of breast feeding. Two hundred and thirty-eight mothers who had
      delivered normal single babies with birth weights greater than 2.5 kg and had
      initiated breast feeding were randomly selected at the maternity hospital,
      Hospital de Clinicas de Porto Alegre, Brazil, and followed by mail questionnaires
      until termination of breast feeding, or until the end of the first year. If no
      reply was received, telephone contact or home visits were made. The group of
      mothers who stopped breast feeding prior to the end of the third month was
      compared with those who extended breast feeding beyond three months with respect
      to socioeconomic, biological, environmental, medical and psychological factors.
      The variables with a significant coefficient of association with early
      termination of breast feeding were maternal education, past experience with
      breast feeding, help of a maid, help with housework provided by a relative,
      breast feeding orientation during prenatal care and encouragement from the
      husband. These factors act simultaneously, with interactions among them.

PMID- 1392359
TI  - Temperature, metabolic adaptation and crying in healthy full-term newborns cared
      for skin-to-skin or in a cot.
AB  - The aim of the present study was to compare temperatures, metabolic adaptation
      and crying behavior in 50 healthy, full-term, newborn infants who were randomized
      to be kept either skin-to-skin with the mother or next to the mother in a cot
      "separated". The babies were studied during the first 90 min after birth.
      Axillary and skin temperatures were significantly higher in the skin-to-skin
      group; at 90 min after birth blood glucose was also significantly higher and the
      return towards zero of the negative base-excess was more rapid as compared to the
      "separated" group. Babies kept in cots cried significantly more than those kept
      skin-to-skin with the mother. Keeping the baby skin-to-skin with the mother
      preserves energy and accelerates metabolic adaptation and may increase the well
      being of the newborn.

PMID- 1392360
TI  - The influence of the basal yellow colour of the skin at birth on later jaundice
      meter readings in mature newborn infants.
AB  - The yellow colour of the skin was measured just after birth in 100 mature
      newborns using a jaundice meter. The skin colour was significantly correlated to
      the cord bilirubin concentration (rho = 0.26, p = 0.009), but unrelated to cord
      reserve albumin concentration, cord albumin concentration, cord haemoglobin
      concentration, birth weight and gestational age. In 123 other mature newborns,
      the basal yellow colour of the skin was estimated on the basis of meter readings
      taken just after birth. Correction of meter readings taken on the third postnatal
      day for the basal yellow skin colour improved neither the correlation between the
      meter readings and the bilirubin concentration nor the ability of the meter
      readings to predict hyperbilirubinaemia.

PMID- 1392361
TI  - Cardiovascular effects of carbon dioxide in ventilated preterm infants.
AB  - Sick preterm infants may, under certain conditions, demonstrate blood pressure
      passive cerebral blood flow in response to changes in arterial carbon dioxide
      tension. Blood pressure in turn depends on cardiac output and peripheral
      resistance. A Doppler technique for assessing cardiac output compared favourably
      in terms of reproducibility to a thermodilution technique in a group of infants
      undergoing cardiac catheterization for congenital heart disease. Doppler was
      subsequently used to monitor changes in cardiac output following an increase in
      arterial carbon dioxide tension of 1 kPa in 25 ventilated preterm infants. Blood
      pressure increased significantly (p = 0.006). However, heart rate did not change
      significantly (p = 0.16) and, in addition, both stroke and minute volume
      decreased (p = 0.023, p = 0.02, respectively). This suggests that accompanying
      changes in components of peripheral resistance exert important effects on blood
      pressure in the preterm neonate in response to changes in arterial carbon dioxide
      tension.

PMID- 1392362
TI  - Cerebral and aortic blood flow velocity patterns in preterm infants receiving
      prophylactic surfactant treatment.
AB  - Blood velocity in the internal carotid artery (ICA) and in the descending
      thoracic aorta (DAo) was investigated used Duplex-Doppler ultrasound in 14
      infants of less than 30 weeks gestation, treated prophylactically with
      surfactant, and in 11 comparable infants with relatively mature lungs who served
      as controls. After surfactant administration, blood gases, pH or FiO2 were not
      different between the groups. Temporal mean blood velocity in the ICA was used as
      a relative measure of cerebral flow (TMFV-cer), and its coefficient of variation
      (CV-cer) was used to assess fluctuations in cerebral blood velocity. The
      pulsatility index (PI) in the ICA (PI-cer) and DAo (PI-DAo) was used to estimate
      if a left-to-right shunt was present. During surfactant instillation TMFV-cer was
      abnormally low and CV-cer indicated a fluctuating cerebral blood velocity. At 10
      min after surfactant administration, TMFV-cer of the treated infants was higher
      compared to the controls, while CV-cer was stable in both groups. PI-cer and PI
      DAo were abnormally high during the first hour of life after surfactant
      treatment, suggesting a left-to-right shunt without, however, clinical signs of a
      hemodynamically important ductus arteriosus. We suggest that cerebral perfusion
      is affected during and at 10 min after surfactant instillation. Left-to-right
      shunting appears to be a common event following surfactant treatment.

PMID- 1392364
TI  - The effect of dietary pectin on rapid catch-up weight gain and urea kinetics in
      children recovering from severe undernutrition.
AB  - The rates of weight gain and urea kinetics were measured in 12 children receiving
      one of two energy dense, isonitrogenous formulae (711 kJ/kg/day, 170 kcal/kg/day)
      during recovery from severe undernutrition. Both formulations contained added
      arachis oil but in one a source of complex carbohydrate was added in the form of
      pectin (3.4% of total energy). The children taking the pectin diet had a rate of
      weight gain which was highly significantly less (7 g/kg/day) than the children
      not receiving pectin (14 g/kg/day). Urea production was significantly less on the
      pectin diet (0.37 +/- 0.07 vs 0.55 +/- 0.18 gN/kg/day). On the pectin diet there
      was a reduction in the rate of excretion of urea in urine and in the rate at
      which urea nitrogen was salvaged by the lower bowel, but these differences failed
      to reach statistical significance.

PMID- 1392363
TI  - Human gastric lipase: ontogeny and variations in children.
AB  - The aim of this study was to investigate the precise origin of the acid pre
      duodenal lipase during human development and to evaluate its possible changes, at
      the tissue level, in children with gastritis or pancreatic insufficiency. Human
      gastric lipase appears around the 11th week of gestation and increases slowly
      during pre- and postnatal development. It is localized in the fundus of the
      stomach without any lingual localization. Human gastric lipase reaches its adult
      level in the third month of life, and does not vary in relation to pancreatic
      insufficiency. It is only rarely impaired during gastritis.

PMID- 1392365
TI  - Follow-up of nutritional status and dietary survey in children with cow's milk
      allergy.
AB  - The nutritional status of children with cow's milk allergy was followed during an
      elimination diet in 19 children (9 boys and 10 girls) beginning at the mean age
      of two years (range 0.6-4.1 years). The cow's milk allergy had been verified in
      hospital by a challenge test at a mean age of 0.9 years (range 0.2-1.9 years).
      Weight, height and laboratory indices to test protein, mineral and vitamin status
      were measured at three follow-up visits at three-month intervals. In addition to
      cow's milk allergy all these children had some other food allergies, and six of
      the 19 children were allergic to soy protein. Only two of the 19 children were
      given a soy-based formula. In the diets of the other children, cow's milk was
      replaced by increasing amounts of other foodstuffs and supplementary calcium. At
      the beginning of the study the relative heights of the children were slightly
      retarded (-0.6 SD) and remained unchanged during follow-up (-0.8 SD at the end of
      the study). The relative weights were found to be decreased during follow-up (p
      less than 0.05). There was a significant reduction in serum prealbumin values;
      eight of the 19 children showed abnormally low values. Low serum zinc values were
      seen in 12 children. Serum iron concentration was low in two children and two had
      high serum alkaline phosphatase values. Seven-day food recording indicated that
      dietary intake of energy was below the recommendation in some children, but
      protein intake was high. Some children had low intakes of riboflavin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1392366
TI  - Genetic analysis of cystic fibrosis in Denmark. Implications for genetic
      counselling, carrier diagnosis and prenatal diagnosis.
AB  - Cystic fibrosis is the most common, severe, inherited disease in the Caucasian
      population. As a consequence, the demand for genetic counselling of patients with
      cystic fibrosis and their families is large. In Denmark the incidence of cystic
      fibrosis is 1:4700, which is quite low compared to other European countries. We
      have investigated 268 Danish cystic fibrosis patients with respect to DNA markers
      (haplotypes) and the most common mutation delta F508. The delta F508 mutation is
      found on 88% of all cystic fibrosis chromosomes, the highest frequency reported
      so far. This had had an important impact on genetic counselling, prenatal
      diagnosis and eventually population screening. In the Danish population 78% of
      all couples at risk will be informative for delta F508 and will be identifiable
      by simple screening methods.

PMID- 1392367
TI  - Eight-year follow-up of pulmonary function and oxygen uptake during exercise in
      16-year-old males with cystic fibrosis.
AB  - Eight of nine Norwegian 16-year-old males with cystic fibrosis, and six age
      matched, physically active controls were included in an eight-year follow-up
      study, involving pulmonary and bicycle exercise testing. The individual's level
      of regular physical exercise was registered, and we investigated whether or not
      this could be correlated to changes in clinical status, lung function and maximal
      oxygen uptake. Four males with cystic fibrosis trained regularly for 4-7 h
      weekly, while the other four patients did no regular exercise. Three of the
      latter died during the study, and the fourth male in the non-training group
      deteriorated significantly during the study period of eight years. The four males
      in the training group showed improvement in lung function parameters and maximal
      oxygen uptake, but two of them had more marked obstructive lung disease after the
      age of 24 years. Even though the sample was small, and several other factors may
      influence the results, the study indicates that regular physical exercise has
      beneficial long-term effects on clinical status, lung function and physical
      fitness in adolescent cystic fibrosis males.

PMID- 1392368
TI  - Assessment of thyroidal "C" cell secretion in osteoporotic girls with Turner's
      syndrome. Basal and calcium-stimulated levels of total calcitonin, extractable
      calcitonin and katakalcin.
AB  - Osteoporosis is a common finding in Turner's syndrome. To test the hypothesis
      that calcitonin deficiency may contribute to bone mineral loss in Turner's
      syndrome, we studied basal and calcium-stimulated (2 mg/kg body weight in 5 min)
      levels of total calcitonin, extractable calcitonin and katacalcin in 15 girls
      with Turner's syndrome and osteoporosis. Fifteen age-matched healthy girls were
      studied as controls. Both basal calcitonin (total and extractable) and katacalcin
      values were not significantly different in patients with Turner's syndrome in
      comparison with those of the controls. The calcium stimulation test showed a
      similar "C" cell secretory reserve in both groups. The calculation of delta
      CT/delta iCa of total and extractable calcitonin and delta KC/delta iCa, which
      accounts for individual variations in serum ionized calcium increases, did not
      show any significant difference between girls with Turner's syndrome and
      controls. We conclude that calcitonin deficiency is not a causative factor of
      osteoporosis in girls with Turner's syndrome and that in this syndrome long-life
      estrogen deficiency does not impair "C" cell secretory activity.

PMID- 1392369
TI  - Hypoxaemia in infants with respiratory tract infections.
AB  - Nineteen infants who were graduates from special care baby units underwent two
      overnight tape recordings of oxygen saturation (SaO2) and breathing movements;
      one during an upper (n = 12) or lower (n = 7) respiratory tract infection and the
      other when free of infection. Baseline SaO2 was lower during infection (median
      99.6 vs 100%, p less than 0.01), with four patients having values (84.3-95.5%)
      below the normal lower limit for full-term infants (97%). The median number of
      apnoeic pauses was also lower during respiratory tract infection (4.7 vs 15.7/h,
      p less than 0.02). The median number of episodic desaturations (SaO2 less than or
      equal to 80%) did not change significantly (1.3 vs 1.9/h, p greater than 0.05),
      with the exception of one patient who had extremely increased values during
      infection for both apnoeic pauses (63/h) and desaturations (112/h). No infant,
      however, was considered clinically hypoxaemic. Clinically unsuspected hypoxaemia
      may thus occur during respiratory tract infection in a proportion of infants
      graduating from special care baby units. Such hypoxaemia may have potentially
      deleterious effects.

PMID- 1392370
TI  - Enhanced basal and stimulated PMN chemiluminescence activity in children with
      atopic dermatitis: stimulatory role of colonizing staphylococci?
AB  - In adults, intense staphylococcal skin colonization and hyperactivity of
      polymorphonuclear leukocyte (PMN) oxidative metabolism are characteristic
      features of atopic dermatitis. Precise data on childhood atopic dermatitis are
      lacking. In a prospective study we analysed the PMN chemiluminescence activity
      with special reference to staphylococcal stimuli in 19 children (mean age 6.2
      years) with mild to moderate atopic dermatitis. Staphylococcus aureus was
      isolated from 17/19 (90%) of children with atopic dermatitis and 13/45 (29%) of
      healthy age-matched controls (p less than 0.001). The mean (SEM)
      chemiluminescence activity of unstimulated atopic dermatitis-PMN was 0.34 (0.009)
      (controls: 0.092 (0.003) x 10(6) cpm/10(6) PMN/min (p less than 0.02).
      Staphylococcal antigens (S. aureus, S. epidermidis, S. haemolyticus) induced a
      1.9-3.1-fold higher peak chemiluminescence response in children with atopic
      dermatitis than in controls (p less than 0.05). The time interval until peak
      chemiluminescence activity was considerably shorter for all stimuli in atopic
      dermatitis. We conclude that PMN of children with atopic dermatitis are "primed",
      showing enhanced release of reactive oxygen metabolites even in the "resting"
      state, and are easily stimulated by staphylococcal antigens present on the skin
      of patients with atopic dermatitis from early childhood on. We speculate that PMN
      hyperreactivity may contribute to chronic skin damage in atopic dermatitis.

PMID- 1392371
TI  - Recurrent parotid swelling in children: clinical features useful for differential
      diagnosis of Sjogren's syndrome.
AB  - Immunological evaluations were performed in 59 children with at least five
      episodes of parotid swelling. Autoantibody(ies) was transiently or persistently
      detected in 12 (20%) of 59 patients with recurrent parotitis. Three of the 12
      children with autoantibodies were diagnosed as having Sjogren's syndrome. The
      mean age at onset of parotid swelling in Sjogren's syndrome was significantly
      higher than that of recurrent parotitis of unknown etiology. The present study
      and the review of the literature suggest that patients with the onset of parotid
      swelling at age five years or over deserve screening for underlying systemic
      immune disorders.

PMID- 1392373
TI  - Wiskott-Aldrich syndrome: case presentation with molecular genetic analysis for
      clonality.

PMID- 1392372
TI  - Cigarette smoke exposure and development of infants throughout the first year of
      life: influence of passive smoking and nursing on cotinine levels in breast milk
      and infant's urine.
AB  - The effects of smoke exposure via mothers' milk and/or via passive smoking during
      the first year of life were investigated in a prospective longitudinal matched
      pair study. The somatic and mental development of 69 infants whose mothers smoked
      more than five cigarettes per day throughout pregnancy and continued smoking
      after childbirth were compared with 69 children of non-smoking mothers. At birth,
      mean body weight of neonates from smoking mothers was significantly lower than
      the weight of neonates from non-smoking mothers. This weight difference between
      the two groups was no longer significant in infants at 12 months of age. With the
      methods employed by the authors, neither psychomotor nor mental development was
      affected by smoke exposure during pregnancy and early infancy. Infections of the
      lower respiratory tract were more frequent in the children of smoking mothers.
      These mothers weaned their babies earlier than non-smokers, but the different
      feeding behaviour did not influence any of the clinical parameters that were
      investigated in this study. In order to evaluate the extent of smoke exposure,
      cotinine was measured in children's urine and in breast milk once a month
      throughout the first year of life. Cotinine in the urine was significantly
      dependent on feeding behaviour: infants breast fed showed concentrations 10-fold
      higher than those who were bottle fed. Cotinine excretion in urine of infants
      from smoking mothers, who were not breast fed (nicotine exposure via passive
      smoking only) was even higher than that of adult passive smokers. If infants from
      smoking mothers were breast fed, their urinary cotinine excretion was in the
      range of adult smokers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392374
TI  - Plasma endotoxin and glycolipid antibodies in children with meningitis.

PMID- 1392375
TI  - Polycystic kidneys in Ivemark's syndrome.

PMID- 1392376
TI  - A therapeutic alternative for haemophiliacs with inhibitors.

PMID- 1392378
TI  - Chronic active hepatitis with renal tubular acidosis presenting as hypokalemic
      periodic paralysis with respiratory failure.

PMID- 1392377
TI  - Recombinant factor VIIa in an infant with haemophilia A and inhibitors.
AB  - Post-traumatic bleeding from the gingiva in a 16-month-old boy with severe
      haemophilia A did not stop after treatment with factor VIII concentrate and
      tranexamic acid, and it was demonstrated that he had developed antibodies to
      factor VIII. Treatment with recombinant factor VIIa 60-90 micrograms/kg body
      weight four to eight times daily, together with local measures, stopped the
      bleeding and no complications were seen.

PMID- 1392380
TI  - Feeding problems in an affluent society. Follow-up at four years of age in
      children with early refusal to eat.
AB  - Twenty-four children, previously investigated at 3-12 months of age for refusal
      to eat during at least four weeks with no apparent medical cause, were followed
      up prospectively and reinvestigated at four years of age. Comparisons were made
      with 38 controls, selected from the same child health care districts. Information
      was obtained from parental interviews, medical records and assessments by a
      speech therapist. At four years of age, 17 of the 24 children with early refusal
      to eat (71%) were reported by the parents to still have feeding problems and 10
      (42%) were reported as hyperactive. Compared to the controls, the children with
      early refusal to eat seemed to have an equally good prognosis with respect to
      health, growth and development, but were at risk of later problems with their
      eating patterns and behaviour.

PMID- 1392379
TI  - Normal Y sequences in Smith-Lemli-Opitz syndrome with total failure of
      masculinization.
AB  - We report an infant with characteristics of Smith-Lemli-Opitz syndrome who had
      anteverted nostrils, apparently low-set ears, micrognathia, high-arched palate,
      cleft palate, growth and psychomotor retardation, hypotonia, poor suck, cerebral
      hypotrophy and double renal pelvis and ureter. An EEG showed spike waves in the
      right temporal area. The patient appeared to have normal internal and external
      genitalia of the female type. Both ovaries were dysplastic. The karyotype was
      46,XY. All of 26 loci on the Y chromosome were positive including SRY, a
      candidate gene for TDF.

PMID- 1392381
TI  - Increasing incidence of childhood coeliac disease in Sweden. Results of a
      national study.
AB  - A survey of the incidence of coeliac disease was carried out by asking all 43
      paediatric departments in Sweden to report the number of children born between
      1978 and 1987 in whom coeliac disease had been diagnosed. Thirty-four departments
      representing a population of 7.18 million reported 1944 cases of coeliac disease
      among 804,935 children born between 1978 and 1987. The cumulative incidence of
      coeliac disease was 1.7 per 1000 live births in children born between 1978 and
      1982 and doubled to 3.5 per 1000 live births in children born after 1982. The
      highest incidence was found in the southern and south-eastern regions of the
      country. The observed increase may have been influenced by changes in infant
      feeding practices such as the postponed age of introduction of gluten from four
      to six months of age and an increase in gluten content of proprietary baby foods.

PMID- 1392383
TI  - The status of lactose absorption in Hong Kong Chinese children.
AB  - Lactose malabsorption was investigated in 169 Chinese children aged between two
      and 16 years using the breath hydrogen test. The challenge was either lactose
      solution (1 g/kg) or cow's milk (10 ml/kg). Overall, 68% of the children showed a
      significant increase in breath hydrogen following the lactose challenge while
      only 17% showed an increase after the cow's milk challenge and 13% after both
      challenges. The number of malabsorbers increased significantly (p less than
      0.001) with age and no associated gastrointestinal symptoms or signs were found
      in any of the children following the challenges, suggesting a gradual and partial
      loss of intestinal lactase activity. We conclude that the prevalence of lactose
      malabsorption in Hong Kong children is very high using the standard lactose
      tolerance test but when a more realistic amount of lactose and a natural medium
      such as a glass of milk is used as the challenge, the number of malabsorbers
      becomes small and clinically insignificant.

PMID- 1392384
TI  - Schistosoma haematobium: a neglected common parasitic disease of childhood in
      Nigeria. Incidence and intensity of infection.
AB  - A prospective and cross-sectional study was carried out in various communities in
      Kwara State, Nigeria, to access the status and implications of urinary
      schistosomiasis among schoolchildren. Of 425 pupils examined in nine communities,
      193 (45.4%) were infected. Infection rates for boys (44.7%) and girls (47.9%)
      were not significantly different (p greater than 0.5). Children between 11 and 13
      years of age had the highest incidence rates (33.6%). However, the percentage of
      children (25.9%) excreting at least 1000 eggs per 10 ml of urine sample during
      their first decade of life was significantly higher (p less than 0.01) than for
      older pupils. The health implications of schistosomiasis acquired early in life,
      as in this study, are highlighted in the discussion.

PMID- 1392382
TI  - Diabetes-related autoantibodies do appear in children with coeliac disease.
AB  - Humoral immune factors related to type 1 diabetes have been investigated in
      children with coeliac disease. Anti-insulin (IAAb), immunoglobulin (alpha IgAb),
      islet cell (ICA) and glucagon autoantibodies were examined in 15 children with
      coeliac disease at diagnosis (group 1), in 15 children with coeliac disease
      following a gluten-free diet (group 2) and in 30 control patients (groups 3 and
      4). IAAb were present in 27% of group 1 and in 20% of group 2 patients and alpha
      IgAb were significantly increased in group 1 and 2 patients; two patients in
      group 2 were positive for ICA; none of the coeliac disease patients were positive
      for anti-glucagon antibodies. The levels of anti-gliadin antibodies in group 1
      were positively correlated with those of alpha IgAb. Coeliac disease-related HLA
      antigens were not correlated with antibody presence. The presence of diabetes
      related humoral immune factors in coeliac disease raises the question as to
      whether or not they are predictive of subclinical pancreatic damage or whether
      they are simply indicators of a more general autoimmune diathesis.

PMID- 1392385
TI  - Obstructive sleep apnea in Arnold-Chiari malformation treated with acetazolamide.
AB  - We studied respiratory patterns and transcutaneous gas pressures in two infants
      with Arnold-Chiari type II malformation referred to us due to repeated episodes
      of stridor and cyanosis. During both active and quiet sleep, respiration was
      irregular and absent or inverse thoracic breathing movements and frequent
      decreases in oxygen saturation to below 80% were observed. When breathing air
      with 2% CO2 or when given acetazolamide 10 mg/kg, chest wall movements normalized
      and oxygenation increased to near normal levels. After three months of treatment
      with acetazolamide 20 mg/kg/24 h no further episodes of hypoventilation or
      hypoxemia were observed and further treatment could be discontinued. We conclude
      that stimulation of respiration by CO2 or by acetazolamide appears to recruit
      chest wall muscles and promote upper airway patency in Arnold-Chiari
      malformation. A treatment trial with acetazolamide seems justifiable in these
      infants when respiratory problems are present.

PMID- 1392386
TI  - Neuroradiological findings in children with congenital myotonic dystrophy.
AB  - We studied seven children with congenital myotonic dystrophy, aged 2.1-8.3 years,
      and the results of computed tomography and magnetic resonance imaging of the
      brain were analyzed and neurological development was assessed from the neonatal
      period. We found that ventricular dilatation that had been seen on the first day
      of life in two of three infants had not progressed in sequential follow-up
      computed tomography scans taken at intervals of one to six years. Also, in T2
      weighted magnetic resonance imagings, areas of periventricular hyperintensity
      were identified in all children, as well as areas of subcortical hyperintensity
      in one child. Further, an asphyxial episode had occurred at birth in five
      patients and the extent of the periventricular hyperintensity was found to
      correlate significantly with Apgar scores, indicating that the degree of
      perinatal asphyxia that had occurred was responsible for the abnormalities
      uncovered by the magnetic resonance imagings. However, there was no correlation
      between the neurodevelopment outcome and the extent of the periventricular
      hyperintensity or ventriculomegaly. Therefore, in patients with congenital
      myotonic dystrophy, a neonatal episode of asphyxia can be responsible for a
      finding of periventricular hyperintensity, but it is unlikely that an integral
      part of the mental retardation is attributable to brain damage due to perinatal
      asphyxia.

PMID- 1392387
TI  - Sleep and wakefulness in preadolescent children with deficits in attention, motor
      control and perception.
AB  - In 10 children with deficits in attention, motor control and perception (DAMP),
      the relation between daytime vigilance and night-time sleep quality was examined
      with polygraphic sleep recordings, multiple sleep latency tests and measurements
      of reaction times. Two girls and eight boys, 6-12 years of age were studied.
      Eighteen normal children served as controls. Normal sleep regulation and sleep
      quality was found, but the children with DAMP tolerated the recording procedure
      less well than the controls. Most patients did not suffer from increased daytime
      sleepiness, but at MSLT 3, patients had short sleep latencies as in daytime
      hypersomnolence. Reaction times were significantly longer among the patients than
      among the controls. It is proposed that the findings may be related to functional
      changes in the forebrain.

PMID- 1392388
TI  - Well-being of children with chronic illness. A population-based study in a
      Swedish primary care district.
AB  - According to a previous study, 8% of all children in Dalby primary care district
      were chronically ill. The impact of the illness on the children's well-being was
      investigated using parental questionnaires. No difference in socio-demographic
      variables was found between responders (70%) and non-responders. The study
      comprised 98 index and 168 control children. Comfort and well-being in school and
      pre-school were lower among the index than among the control children and lower
      among the index children in normal compared with special schools. According to
      the parents many teachers had insufficient knowledge of disorders/handicaps.
      Children with a physical disability more often had special remedial education
      compared with healthy children. The chronically ill children were bullied more
      often, had fewer contacts with peers and more emotional problems than the control
      group. Improved knowledge of chronic childhood disorders/disabilities and
      recognition of the psychosocial consequences at school/pre-school and in the
      child health services is advocated.

PMID- 1392389
TI  - Infant feeding and Schonlein-Henoch purpura.

PMID- 1392390
TI  - C-reactive protein in hepatitis A.

PMID- 1392391
TI  - Reasons for low tetanus immunization coverage in a hospital: a focus group
      investigation.

PMID- 1392392
TI  - Further evidence of elevated bone resorption in Ullrich-Turner syndrome by
      measuring urinary galactosyl-hydroxylysine.

PMID- 1392393
TI  - Hoarseness in a child with gastroesophageal reflux.
AB  - Hoarseness is not generally appreciated to be a manifestation of pediatric
      gastroesophageal reflux. We describe a case in which treatment of well-documented
      gastroesophageal reflux and esophagitis in a young girl with hoarseness and
      nocturnal cough led to resolution of these symptoms. Possible pathogenetic
      mechanisms and the difficulty in associating hoarseness with reflux by standard
      reflux testing are discussed.

PMID- 1392394
TI  - Progressive idiopathic cholestasis presenting with profuse watery diarrhoea and
      recurrent infections (Byler's disease).
AB  - The second child of healthy unrelated parents presented with chronic diarrhoea
      since the age of two months, initially associated with non-characteristic liver
      involvement. Recurrent infections, severe failure to thrive and various metabolic
      deficiencies complicated the further course, as well as profuse watery diarrhoea
      with elevated regulatory gut peptides, responding only to somatostatin analog
      treatment. At 22 months of age, intermittent cholestasis with permanently normal
      serum gamma-glutamyltransferase was evident. The child died of fulminant purulent
      meningitis at the age of three years six months. Liver histology showed
      intrahepatic cholestasis, bile duct paucity with focal proliferation as well as
      slight portal and intralobular fibrosis. The clinical, biochemical and
      histopathological findings were indicative of Byler's disease.

PMID- 1392395
TI  - Septo-optic dysplasia and growth hormone deficiency: accelerated pubertal
      maturation during GH therapy.
AB  - We report four patients (three male, one female) with septo-optic dysplasia and
      growth hormone deficiency. All had GH therapy for a period of four to eight years
      until reaching final height. In all four cases bone maturation during puberty was
      accelerated (1.4 to 1.9 "years"/year), resulting in a final height which was
      clearly below the predicted height. The progress of pubertal stages was very
      short in all patients. In three patients TSH and prolactin release after TRH
      stimulation were increased. These data support a hypothalamic original of the
      endocrine disorder. Insufficient GH release, even after repeated GHRH
      stimulation, is in contrast to this assumption. In one case there was a late
      manifestation of neurohormonal diabetes insipidus, which indicates the
      possibility of later disease progression. MR imaging of the brain demonstrated
      variable malformation of the septum pellucidum, chiasma and nervus opticus or the
      pituitary gland, respectively.

PMID- 1392396
TI  - Phenytoin-induced IgG2 and IgG4 deficiencies in a patient with epilepsy.
AB  - A five-year-old girl with epilepsy and recurrent respiratory infections was
      investigated for serum IgG subclass concentrations. She was diagnosed as having a
      combined deficiency of IgG2 and IgG4 with a decreased serum concentration of IgA
      and IgG3 and was given replacement therapy with i.v. immunoglobulins. Since then,
      she has been free from respiratory infections. After phenytoin therapy was
      stopped, IgG subclass deficiency improved. This case describes the further action
      of phenytoin on the immune system, adding IgG subclass deficiency to the list.

PMID- 1392397
TI  - Self-inflicted ocular mutilation in the pediatric age group.
AB  - Three mentally retarded children with severe self-inflicted ocular injuries are
      presented. All three suffered from severe ocular injuries including retinal
      detachment resulting in progressive visual loss and even blindness. Self
      inflicted injuries to the eyes, including self enucleation, is an extremely
      uncommon form of behavior, rarely encountered by pediatricians. The risk of
      ocular morbidity is high if the diagnosis is overlooked. Technical advances in
      ophthalmology permit much improvement in some formerly hopeless cases of ocular
      self-mutilation, but there is still no accurate method to repair destroyed
      retinal or nervous tissue. Early identification of patients at risk of ocular
      self-mutilation is essential in order to prevent or minimize such severe ocular
      injuries.

PMID- 1392398
TI  - Congenital sideroblastic anaemia with intrauterine symptoms and early lethal
      outcome.
AB  - Sideroblastic anaemia is a rare disease, which most often presents in early
      childhood. A case of ringed sideroblastic anaemia with onset in early foetal life
      in a female infant, resulting in severe intrauterine symptoms, is reported. Six
      weeks after birth a bone marrow examination revealed a large amount of typical
      ringed sideroblasts, thus establishing the diagnosis. In spite of repeated blood
      transfusions, the haemoglobin content gradually decreased. The condition was
      refractory to pyridoxal phosphate treatment and continued to deteriorate with
      lethal outcome four months after birth.

PMID- 1392399
TI  - 13th Nordic congress of perinatal medicine. Copenhagen, 13-15 August 1992.
      Abstracts.

PMID- 1392400
TI  - Susceptibility of human leukemia to allogeneic and autologous lymphokine
      activated killer cell activity: analysis of 252 samples.
AB  - The present study investigated the susceptibility of human leukemia cells to
      allogeneic lymphocytes with lymphokine-activated killer (LAK) activity from
      normal donors and autologous LAK activity from patients in complete remission.
      LAK activity was generated from peripheral-blood mononuclear cells cultured for 6
      days with 1,000 U/ml recombinant interleukin-2 (IL-2). Cytotoxicity was evaluated
      using a standard 4-hour chromium release assay. Susceptibility of leukemic cells
      to LAK was defined on the basis of the mean Cr release in 52 samples of normal
      bone marrow cells. Using allogeneic LAK, we examined leukemic cells from bone
      marrow or peripheral blood of 252 patients [102 with acute myeloid leukemia
      (AML), 99 with acute lymphoblastic leukemia (ALL), 13 with chronic myelogenous
      leukemia in blast crisis (CML-BC) and 38 with chronic leukemias of various
      types]. A significant lysis could be detected in 62% of all leukemias tested (in
      68% of AML, 60% ALL, 92% CML-BC, 39% chronic leukemias). The mean chromium
      release (effector-to-target cell ratio 50:1) was 28.8 +/- 13.5% for LAK-sensitive
      leukemias versus 5.2 +/- 3.2% for resistant leukemias. We observed a distinct
      susceptibility of various leukemia subtypes. LAK cytotoxicity against autologous
      leukemia cells was examined in 40 leukemia patients in complete remission (24
      AML, 16 ALL). 63% of the patients developed a significant cytotoxicity against
      their autologous leukemia cells. Regarding mean Cr releases, the efficiency of
      allogeneic LAK activity of normal donors did not differ significantly from that
      of autologous LAK activity of patients in complete remission against the same
      leukemic target cells. Analysis of our data revealed that examinations with
      allogeneic LAK activity make it possible to predict whether patients will develop
      significant in vitro killing of their autologous leukemia cells during complete
      remission. These results may be of particular importance in determining which
      patients could benefit from immunologic therapy modalities and in scheduling
      immunotherapy. Further clinical studies are necessary to ascertain the clinical
      significance of therapeutic approaches with IL-2 or adoptive cellular
      immunotherapy combined with IL-2 for treatment of human leukemia.

PMID- 1392401
TI  - In vivo and ex vivo antitumor activity in patients receiving low-dose
      subcutaneous recombinant interleukin-2.
AB  - Alterations in cell-mediated cytotoxicity levels were studied in patients
      receiving recombinant interleukin-2 (rIL-2) via subcutaneous injection. Fourteen
      outpatients, aged 36-68 years, with progressive metastatic malignancies, were
      treated with weekly escalated doses of rIL-2, starting at 1.8 IU/m2/day for 6
      days a week, up to 14.4 IU/m2/day during the 4th week of therapy. Patients
      presenting with stable disease thereafter were started on maintenance therapy and
      received 10.8 IU/m2 once weekly for up to 12 weeks. Patient mononuclear cells
      were isolated from fresh peripheral blood at various times throughout the
      treatment. Cells were assayed prior to and after further in vitro stimulation by
      rIL-2 (600 IU/ml for 7 days). Natural killing (NK) activity was measured by
      cytolysis of K 562 target cells, and lymphokine-activated killing (LAK) was
      determined by cytotoxicity against Daudi targets, respectively, in four
      effector:target ratios (E:T), using a standard 2-hour europium3+ release assay.
      Spontaneous NK cell function (E:T = 25:1) of freshly isolated peripheral blood
      mononuclear cells (PBMC) was enhanced significantly after 28 days of therapy
      (27.8 vs. 9.1% on day 0). LAK activity also markedly increased during therapy
      (26.2 vs. 5.4% on day 0). Further in vitro culture of these PBMC in the presence
      of rIL-2 resulted in day 28 non-MHC-restricted cytolytic activity of 63.2% (40.3%
      on day 0) against K 562 targets, and 64.9% (39.6% on day 0) against Daudi
      targets. Activation of cytolytic function by rIL-2 appeared to be dose-dependent,
      as measurable lytic capability decreased throughout maintenance therapy, while
      neither sex nor tumor entity prior to therapy or clinical response were
      correlated with cytotoxicity levels. Taken together, our observations demonstrate
      that stimulation of the non-MHC-restricted pathway of cytolytic activation, as
      measured by lysis of target cells, arises in patients treated with rIL-2 doses 5-
      to 30-fold lower than used previously in intravenous protocols, connecting
      effective clinical response rates with acceptable tolerability.

PMID- 1392402
TI  - Activation of human peripheral-blood-derived monocytes by cis
      diamminedichloroplatinum: enhanced tumoricidal activity and secretion of tumor
      necrosis factor-alpha.
AB  - The anticancer agent cis-diamminedichloroplatinum (CDDP) has been shown to have
      immunopotentiating and immuno-suppressive properties depending on the CDDP
      concentration used. Treatment of human peripheral-blood-derived monocytes (PBM)
      in vitro with low concentrations of CDDP resulted in a significant potentiation
      of antitumor cytotoxicity as assessed in an 18-hour 51Cr release assay. The
      potentiation of cytotoxicity by CDDP was also observed with PBM treated with
      recombinant interferon-gamma (rIFN-gamma). The monocyte-mediated cytotoxicity was
      significantly inhibited when antitumor necrosis factor (TNF) antibody was added
      to the assay culture. The role of TNF in the cytotoxic mechanism was further
      corroborated by demonstrating that significant levels of immunoreactive TNF-alpha
      in the supernatants were detected by ELISA. Further, supernatants derived from
      CDDP-treated monocytes were cytotoxic to the TNF-sensitive tumor cells and the
      cytotoxicity was neutralized by the addition of anti-TNF antibody. The secretion
      of TNF-alpha by CDDP-treated monocytes was readily detected as early as 4 h after
      culture and was dependent on de novo protein synthesis as inhibitors of RNA and
      protein synthesis abolished TNF-alpha secretion. Altogether, these results
      demonstrate that CDDP can potentiate monocyte-mediated antitumor cytotoxicity and
      stimulates TNF-alpha synthesis and secretion.

PMID- 1392403
TI  - Regulation of natural killer cell production in bone marrow of mice: no evidence
      for negative feedback control.
AB  - The possible presence of a negative feedback control mechanism regulating natural
      killer (NK) cell production in the bone marrow of B6 mice was investigated by
      depleting NK cells with a single intravenous injection of anti-ASGM1 antibody. At
      times ranging from 1 to 21 days following injection, the response of the bone
      marrow cells to this depletion was assessed by measuring both NK activity against
      YAC-1 target cells in a 51Cr assay and the frequency of NK precursors by limiting
      dilution analysis. For comparison, measurements of lytic activity were also done
      in the peripheral blood and spleen. Anti-ASGM1 injection resulted in a depletion
      of mature NK cell activity in all compartments tested as expected, as well as the
      depletion of NK precursors from the bone marrow. Clearance of the anti-ASGM1 from
      the circulation of recipient mice was biphasic. More than 99% of the antibody was
      eliminated in the first 4 min, while the remaining 0.24% had a half-life in the
      serum of 6 days. Bone marrow was able to produce new lytic NK cells which were
      detectable between days 6 and 10 after depletion. The bone marrow of the NK cell
      depleted mice did not show an 'overshoot' (compensatory increase) in NK cell
      production through day 21 after depletion. It therefore appears that the NK cell
      production in the bone marrow is independent of the activity of the peripheral NK
      cell pool.

PMID- 1392404
TI  - Effects of macrophage colony-stimulating factor on the activities of murine
      monocytes and peritoneal macrophages in vivo.
AB  - The ability of peripheral blood monocytes, granulocytes and resident peritoneal
      macrophages to generate hydrogen peroxide in response to concanavalin A was
      enhanced by a single intravenous injection of macrophage colony-stimulating
      factor (M-CSF) of recombinant human type in AKR mice. In response to phorbol
      myristate acetate, only granulocytes and resident peritoneal macrophages showed
      the enhanced ability. Phagocytosis by those cells was not stimulated by M-CSF.
      Surface marker analysis showed an increased expression of F4/80 and Mac1 on
      monocytes, Mac1 expression on granulocytes and LFA-1 expression on resident
      peritoneal macrophages. Ia antigen on resident peritoneal macrophages was
      suppressed by M-CSF. M-CSF can induce monocytes, granulocytes and resident
      peritoneal macrophages to generate hydrogen peroxide and enhances their
      maturation in vivo.

PMID- 1392405
TI  - Helicobacter pylori: a nihilistic perspective.

PMID- 1392406
TI  - Maintenance therapy for peptic ulcer disease: an overview of medical treatment.
AB  - Peptic ulcer disease is a chronic disorder that manifests as recurrent episodes
      of pain or complications such as bleeding or perforation. Current medical therapy
      with H2-receptor blockers or sucralfate effectively prevents most recurrences
      and, according to clinical trials, may prevent complications. Since this
      treatment does not alter the natural history of peptic ulcer disease, continued
      therapy is needed. Surgical treatment does permanently alter the history of
      recurrence. Medical therapy aimed at eradicating Helicobacter pylori infection is
      an exciting new development and shows promise of a medical "cure" for peptic
      ulcer disease. However, many questions remain unanswered about this treatment.
      This review examines the natural history and long-term treatment of peptic ulcer
      disease.

PMID- 1392407
TI  - Gastroesophageal reflux disease and its consequences.
AB  - Gastroesophageal reflux is a common event characterized by orad movement into the
      esophagus of gastric and/or duodenal contents. Reflux may produce either no
      damage to the esophageal mucosa or erosions, exudates, ulcerations, strictures,
      and/or Barrett's (columnar-lined) esophagus. In addition to the esophagus, all
      the anatomic structures from the pharynx to the lung may be affected by reflux.
      Numerous factors promote abnormal esophageal mucosal contact time with acid and
      pepsin. These include incompetent lower esophageal sphincter, impaired esophageal
      clearance, increased frequency of reflux episodes, delayed gastric emptying, and
      the presence of a hiatal hernia. The relative contribution of each of these
      factors in the pathogenesis of esophageal mucosal disease has not been clearly
      defined. Epidemiologic and clinical data support an association between
      gastroesophageal reflux and pulmonary disease. Most asthmatic patients,
      independent of bronchodilator use, have evidence of gastroesophageal reflux, as
      demonstrated by ambulatory pH testing, endoscopy, and the presence of reflux
      symptoms. Studies with antireflux agents indicate that partial or complete
      symptom relief and healing of esophagitis are obtained in about half the patients
      using H2-receptor antagonists and almost all patients using omeprazole.
      Preliminary evidence suggests that surgical correction of reflux may lead to
      improved pulmonary status. Controlled clinical trials are needed, however, to
      further determine whether effective gastric acid suppression will improve reflux
      associated pulmonary disease.

PMID- 1392408
TI  - Surgical management of peptic ulcer disease.
AB  - Since the advent of H2-receptor antagonists, elective ulcer surgery is rare. The
      need for operation for complications of peptic ulcer disease, however, remains
      unchanged. Highly selective vagotomy is the elective operation of choice for
      duodenal ulcer worldwide. It has few side effects and a mortality that approaches
      0%. Unfortunately, ulcers recur in 10% to 15% of patients, a much higher
      recurrence rate than that seen with vagotomy and antrectomy (less than 1%). The
      latter operation, however, is associated with significant side effects, such as
      dumping syndrome and diarrhea, and a higher operative mortality. The elective
      operation of choice for gastric ulcer is antrectomy. Recent prospective trials
      show that highly selective vagotomy should be performed routinely at the time of
      closure of perforated duodenal ulcer. Neither morbidity nor mortality is
      increased with the procedure, and the 40% to 60% ulcer recurrence rate with
      closure alone is reduced to 2% to 8%.

PMID- 1392409
TI  - Prevention and treatment of ulcers induced by nonsteroidal anti-inflammatory
      drugs.
AB  - Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) can cause varying
      degrees of gastroduodenal mucosal damage. These agents are most frequently used
      for the treatment of rheumatic diseases because they are highly effective in
      reducing joint pain and swelling. Histamine H2-receptor antagonists, omeprazole,
      sucralfate, and misoprostol are drugs available for the treatment of gastric
      mucosal damage caused by NSAIDs. In controlled clinical studies, all these drugs
      effectively heal gastric and duodenal injury if NSAIDs are discontinued. However,
      current data suggest that if NSAIDs are continued while gastrointestinal damage
      is present, only misoprostol and omeprazole have demonstrated efficacy in healing
      gastric mucosal injury. Misoprostol also effectively heals NSAID-induced duodenal
      injury. At this time, no data exist on the efficacy of other antiulcer drugs in
      healing duodenal erosions or ulceration if NSAID administration is continued.
      Regarding prevention of NSAID-induced gastric ulcer, controlled clinical studies
      with H2 antagonists and sucralfate have failed to show any therapeutic benefit.
      Ranitidine, however, has shown efficacy in preventing NSAID-induced duodenal
      ulcers. The coadministration of misoprostol with NSAIDs to patients who have
      either osteoarthritis or rheumatoid arthritis prevents the development of gastric
      and duodenal ulcers. Based on current published information, this property
      distinguishes misoprostol from other antiulcer drugs.

PMID- 1392410
TI  - 29th national meeting. Society for Leukocyte Biology. Charleston, South Carolina,
      December 2-5, 1992. Program and abstracts.

PMID- 1392411
TI  - Society for Leukocyte Biology. Membership directory.

PMID- 1392412
TI  - Classics corner. Robinson, Victor. White caps: the story of nursing, 1946.

PMID- 1392413
TI  - Dialysis nursing in Wisconsin: 1966-1968: contributions of Priscilla Scholl.

PMID- 1392415
TI  - Protein-calorie malnutrition in liver cirrhosis.
AB  - The purpose of this article is to present detailed data on the nutritional
      assessment in cirrhotic patients. The exact frequency and types of malnutrition,
      its associations with the aetiology of liver disease, liver dysfunction and
      clinical staging in liver cirrhosis are unknown. A new classification system is
      presented which may help to suggest some interventional guidelines. Physical
      (anthropometry, 24-h urinary creatinine excretion, bioelectrical impedance
      analysis (BIA), total body potassium counting, ultrasound examination) and
      metabolic (indirect calorimetry) assessment of nutritional status was therefore
      performed in 123 patients with liver cirrhosis, who were considered as potential
      candidates for liver transplantation. Data were related to the clinical,
      biochemical, histological and prognostic data of liver disease. Of our patients
      65% showed some signs of protein-calorie malnutrition as indicated by low body
      cell mass, reduced serum albumin concentrations or abnormal skinfold thickness.
      Of these 34% were considered as "kwashiorkor-like" (normal body composition,
      serum albumin less than 35 g/l), and 18% were "marastic" (reduced body weight,
      body cell mass, and fat mass). However, 49% of the malnourished group had reduced
      body cell mass in association with increased fat mass and frequently presented
      with a normal body weight ("mixed" or "obese" type). Protein-calorie malnutrition
      did not correlate with the aetiology of the disease and biochemical parameters of
      liver function. Malnutrition was observed at all clinical stages but was more
      frequently seen at advanced stages. We conclude that malnutrition associated with
      liver cirrhosis is not a clear phenomenon. Its clinical presentation is
      heterogenous and not reflected by the histological or biochemical parameters of
      liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392414
TI  - Medicobiological and genetic studies on alcoholism. Role of metabolic variation
      and ethnicity on drinking habits, alcohol abuse and alcohol-related mortality.

PMID- 1392417
TI  - Investigations into Ro-specific antibody-associated congenital cardiac conduction
      defects.
AB  - Forty-two babies with different congenital cardiac conduction defects, and in 12
      cases the mothers, were tested for autoantibodies to Ro, La, U1RNP and Sm. Ro
      specific antibodies were detected most frequently. They were to be found in 16
      sera from infants and in 8 maternal serum samples. The occurrence of anti-Ro was
      associated preferentially with several atrioventricular conduction blocks. The
      sex relation of anti-Ro associated congenital heart block did not show a typical
      preference (6 male/10 female). At the time of giving birth, 5 anti-Ro-positive
      mothers did not have any clinical symptoms of rheumatic autoimmune diseases.
      Three of them had a first degree atrioventricular block. Our findings indicate
      that all pregnant women at risk for anti-Ro like connective tissue disease or
      cardiac conduction defects should be tested for these autoantibodies because of
      the suspicion of cardiac conduction abnormalities in the offspring. Anti-Ro
      positive infants should be examined for structural heart disease by
      echocardiography.

PMID- 1392416
TI  - Effect of ethanol and commonly ingested alcoholic beverages on gastric emptying
      and gastrointestinal transit.
AB  - Acute ingestion of pure ethanol has been reported to delay gastric emptying and
      to enhance the propulsive movements of the intestine. The aim of the present
      study was to investigate the comparative effect of beer (7.0% v/v), white wine
      (7.5% v/v), ethanol (7.5% v/v), and water on the gastric emptying of a liquid
      test meal and on the gastrocaecal transit time of lactulose added to the test
      meal. Gastric liquid emptying was assessed by means of a nasogastric intubation
      technique using polyethylene glycol 4000 as the non-absorbable marker. The
      gastrocaecal transit time was evaluated by a hydrogen breath test. Beer (P less
      than 0.001) and white wine (P less than 0.05) significantly accelerated gastric
      emptying in comparison with ethanol of the same concentration. The gastrocaecal
      transit time was significantly shorter when the liquid meal was administered with
      beer compared with ethanol (P less than 0.005) and water (P less than 0.01). The
      constituents in beer and white wine responsible for our observations remain to be
      found.

PMID- 1392418
TI  - Hypofibrinogenemia due to fibrin formation in subserosal type eosinophilic
      gastroenteropathy.
AB  - A 33-year-old woman presented with abdominal pain and distention, diarrhoea and
      marked eosinophilia in blood and ascites. As other causes could be excluded, the
      subserosal type of eosinophilic gastroenteropathy was diagnosed. The low plasma
      fibrinogen level (less than 100 mg/100 ml) found in this patient is an as yet
      undescribed feature. During prednisolone therapy it increased concurrently with
      the fall of blood eosinophils and the relief of clinical symptoms. Interest was
      further directed to the ascitic fluid where not only the presence of eosinophils
      (74%) enveloped in fibrin yarn and of basophils (2%) but also of 24% T
      lymphocytes (among them 75% CD4+, 24% CD8+, 4% CD25+, less than 1% CD19+, less
      than 1% natural killer cells) could be demonstrated. These lymphocytes are likely
      to be the source for lymphokine production chemoattracting eosinophils into the
      intestine. In addition they seem to be involved in IgE hyperproduction, which
      after adequate therapy and complete resolution of the clinical symptoms, tended
      to decrease slowly.

PMID- 1392419
TI  - Filiform polyposis: a case report describing clinical, morphological, and
      immunohistochemical findings.
AB  - Filiform polyposis (FP) is a rare condition of uncertain pathogenesis, 28 cases
      of which have been published since it was first described in 1965. It is usually
      found in association with chronic inflammatory bowel disease, especially Crohn's
      disease and ulcerative colitis. The condition is characterized by the presence of
      numerous, densely packed, filiform polyps in the colon, which may resemble
      villous adenomas on endoscopy. We describe a case of FP occurring in a 33-year
      old man with a 5-year history of Crohn's disease, in whom subtotal colectomy was
      performed because of perforation of the sigmoid colon. Microscopy revealed
      inflammatory pseudopolyps covered by largely normal and non-dysplastic colonic
      epithelium. The neuroendocrine system of the intestine in FP was investigated for
      the first time in this case: marked hyperplasia of endocrine cells immunoreactive
      for serotonin, somatostatin and enteroglucagon and of neural structures
      immunoreactive for substance P and vasoactive intestinal peptide was noted in the
      polyps and the adjacent intestinal mucosa. The patient has experienced no further
      complications in the 12 months since the operation. Medication administered in FP
      depends mainly on the nature of the underlying disease, and the amount of
      information published about this condition is as yet insufficient to allow any
      one specific type of treatment to be recommended. FP alone is not an indication
      for bowel resection but complications, such as massive haemorrhage or intestinal
      obstruction, may necessitate surgical intervention.

PMID- 1392421
TI  - The restriction enzyme Mse I applied for the detection of a possibly common
      mutation of the APRT locus.

PMID- 1392420
TI  - Acquired protein S deficiency.
AB  - Hereditary deficiencies of coagulation inhibitors like antithrombin III, protein
      C and protein S lead to an enhanced incidence of thromboembolic complications.
      Recently, acquired deficiencies of protein S were described in several disease
      states in which thromboembolic complications frequently occur. These acquired
      protein S deficiencies reach--in part--the extent realised by hereditary protein
      S deficiency. Thus, acquired protein S deficiencies seem to be one source of
      thromboembolic complications occurring in nephrotic syndrome, acute phase
      reactions, malignancy and pregnancy. In this presentation disease states
      accompanied by acquired protein S deficiency and the mechanisms leading to these
      alterations are discussed.

PMID- 1392422
TI  - Distribution of lymphocyte subsets and natural killer cells in the human body.
AB  - The frequency and distribution of B and T lymphocyte subsets have been determined
      in many body tissues and fluids by preparing cell suspensions and tissue sections
      from lymphoid and nonlymphoid organs. In humans these studies often concentrate
      on the blood or on one particular cell source for obvious reasons. However, such
      data can only be interpreted correctly if the whole immune system is taken into
      consideration [64]. To facilitate this, reports on the frequencies and the
      absolute numbers of B and T lymphocyte subsets within various human tissues and
      fluids have been collected from a wide variety of journals and are briefly
      summarized here. Since the size of lymphoid organs varies with age (e.g. thymus,
      tonsils), only the data of adult individuals were included, unless otherwise
      stated. Natural killer (NK) cells are morphologically quite similar to
      lymphocytes [59], but very different functionally. For example, they are not able
      to recirculate from the blood via the lymph nodes and the thoracic duct back to
      the blood as lymphocytes do [19]. Thus, human NK cells have been compared with
      lymphocytes with respect to number and distribution.

PMID- 1392423
TI  - Effects of atrial natriuretic factor on anterior pituitary hormone secretion in
      normal man.
AB  - The effects of intravenous human atrial natriuretic factor ANF(99-126)
      administration on anterior pituitary hormone secretion have not been extensively
      investigated in humans. We repeatedly studied 10 healthy volunteers (5 female, 5
      male, aged 28 +/- 2 years) on 2 occasions, 3 days apart. In randomized, single
      blind order, subjects received pretreatment with either placebo or intravenous
      ANF(99-126) (bolus 100 micrograms/kg, 30-min infusion of 0.1 micrograms/kg.min).
      Subsequently on both occasions subjects received a combined intravenous bolus
      injection of pituitary releasing hormones (200 micrograms thyrotropin releasing
      hormone, 100 micrograms gonadotropin releasing hormone and 100 micrograms human
      adrenocorticotropin releasing hormone; Bissendorf, Hannover, FRG). Plasma
      concentrations of adrenocorticotropic hormone (ACTH), cortisol, luteinizing
      hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH),
      thyrotropin (TSH), prolactin, ANF and cyclic guanosine monophosphate (GMP) were
      determined by radioimmunoassay. ANF(99-126) treatment induced a significant
      reduction in basal ACTH plasma concentrations and tended to decrease basal plasma
      cortisol. The TSH response to combined releasing hormone administration was
      significantly diminished after ANF(99-126) pretreatment. In women, the releasing
      hormone induced prolactin increase was reduced after ANF(99-126) pretreatment.
      With the present study design, ANF(99-126) did not alter the basal or releasing
      hormone stimulated plasma concentrations of cortisol, LH, FSH and GH. Releasing
      hormone administration did not affect ANF and cyclic GMP plasma levels. In
      humans, effects of natriuretic peptides on anterior pituitary hormone secretion
      may have to be considered with investigational or therapeutic administration of
      ANF analogues or agents interfering with the ANF metabolism.

PMID- 1392424
TI  - Reduced bone mineral density and low parathyroid hormone levels in patients with
      the adult form of hypophosphatasia.
AB  - Hypophosphatasia is a heritable metabolic bone disease with characteristically
      reduced levels of alkaline phosphatase (ALP) in the blood, liver, kidney and
      bone. ALP levels are normal in the intestine and placenta. About 300 patients
      have been reported so far in the literature. Three kindreds with 52 known
      subjects are described here, whereby 12 subjects could be examined
      osteologically. Four subjects were patients and had clinical signs of the
      disease: spontaneous fractures of the metatarsals or femora and low ALP serum
      levels ranging between 8 and 23 U/l (normal range 40-170 U/l). Four other members
      without fractures had reduced ALP levels; they might be carriers of the disease
      and develop symptoms later in life. The four remaining subjects had normal ALP
      levels and no signs of the disease. Serum levels of intact parathyroid hormone
      (iPTH) were found to be in the lower normal range and serum calcium levels in the
      upper normal range. There was a significant (P less than 0.05) negative
      correlation between iPTH and serum calcium levels (r = -0.78). Urinary calcium
      excretion was increased in 3 subjects with fractures. 25-OH-D3 levels were
      increased in 6 of 8 subjects without any treatment. The bone mineral density
      (BMD) was measured using dual X-ray absorptiometry of the lumbar spine,
      representing mainly trabecular bone, and single-photon absorptiometry of the
      forearm, measuring mainly cortical bone. Z-scores of the spinal bone mass ranged
      between 0.38 and -1.95 SD; Z-scores of the forearm bone mass ranged between 0.53
      and -2.47 SD with the lowest values in patients with fractures.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1392426
TI  - Cause and frequency of posttransfusion hepatitis after open-heart surgery.
AB  - A total of 1476 patients who underwent open-heart surgery between 1986 and 1988
      participated in a prospective study examining posttransfusion hepatitis. They
      received a total of 8327 units of whole blood, packed erythrocytes, or fresh
      frozen plasma. The aminotransferase activities were measured preoperatively and
      1, 2, 3, 4, 6, 9, 12, and 24 weeks after the operation. Thirty-four patients in
      all (2.3% of the transfused patients) developed posttransfusion hepatitis, which
      could be identified as hepatitis B in 1 patient and hepatitis C in 14 patients.
      No cause for posttransfusion hepatitis could be found in 19 cases (hepatitis of
      unknown origin). Hepatitis C became chronic in 5 patients. In contrast to
      hepatitis C, the 19 patients with hepatitis of unknown origin all showed a milder
      clinical course with lower maximal aminotransferase activities and a shorter
      duration of the hepatitis. A chronic course was not observed among them. The
      cause of hepatitis of unknown origin is discussed.

PMID- 1392425
TI  - Testosterone treatment of men with idiopathic hemochromatosis.
AB  - Patients with chronic liver disease usually exhibit low plasma levels of
      testosterone with loss of libido and potency; this is also valid in male patients
      suffering from idiopathic hemochromatosis (IHC), in whom nowadays the diagnosis
      is made at an earlier age. Therefore, the effect of testosterone treatment was
      studied in 10 patients with IHC. After the application of 250 mg testosterone
      enanthate i.m., the plasma testosterone (from 2.4 +/- 1.9 to 20.1 +/- 7.4 ng/ml)
      and estradiol (from 17.4 +/- 6.3 to 38.5 +/- 14.2 pg/ml) levels increased
      significantly. The rise of estradiol was in the range of controls and smaller
      than reported in other chronic liver diseases. In a long-term study, 250 mg
      testosterone enanthate was given 4-weekly for 33-96 months to 5 patients with
      IHC. General well-being, libido, and potency recovered almost immediately. Over a
      treatment period of 27.3 patient years, symptoms of hyperestrogenism
      (gynecomastia) or (portal vein) thrombosis were not seen, both of which had been
      described in patients with alcoholic liver cirrhosis. There was no deterioration
      of liver function. The effect of testosterone treatment on the patients' well
      being and plasma hormone concentrations remained unchanged over the whole period
      of testosterone treatment. Thus, in male patients with IHC and lowered plasma
      testosterone, treatment with testosterone enanthate may be instituted. Because of
      the positive effects on general well-being, liver regeneration capacity, and
      potency, testosterone should especially be administered to younger subjects
      suffering from IHC.

PMID- 1392427
TI  - Failure of vaccination against hepatitis B with Gen H-B-Vax-D in immunosuppressed
      heart transplant recipients.
AB  - Some 86 heart transplant recipients under immunosuppressive therapy were
      vaccinated against hepatitis B using the vaccine Gen H-B-Vax-D, but 95.3% failed
      to develop protective levels of HBs-specific antibody (more than 10 U/l) after
      the third vaccination.

PMID- 1392428
TI  - Treatment of diarrhoea in human immunodeficiency virus-infected patients with
      immunoglobulins from bovine colostrum.
AB  - Diarrhoea and weight loss are found in more than 50% of patients with the
      acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be
      very severe, leading to death even in the absence of opportunistic infections. In
      30% of these patients, enteric pathogens cannot be identified, and approximately
      only half of the identifiable aetiologic agents of diarrhoea in patients infected
      with the human immunodeficiency virus (HIV) were treatable with antibiotics.
      Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain
      high titers of antibodies against a wide range of bacterial, viral and protozoal
      pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite
      resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37
      immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2
      patients with common variable immunodeficiency (CVID), one unidentified
      immunodeficiency, five patients with graft versus host disease (GvHD) following
      bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days).
      Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV
      infected patients 21 gave good results leading to transient (10 days) or long
      lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily
      stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV
      infected patients showed no response. The diarrhoea recurred in 12 patients
      within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4
      weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following
      oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392429
TI  - Long-term therapy with cyclosporin A does not influence serum concentrations of
      vitamin D metabolites in patients with multiple sclerosis.
AB  - Animal studies have shown that cyclosporin A (CyA) stimulates renal 25
      hydroxyvitamin D3 [25(OH)D3]-1 alpha-hydroxylase activity; in contrast, studies
      in renal transplant recipients indirectly suggest that CyA reduces 1 alpha,25
      dihydroxyvitamin D3 [1,25(OH)2D3] production. To clarify the effect of CyA on
      vitamin D metabolite concentrations, we measured parameters of calcium metabolism
      in 37 CyA-treated patients (median trough whole blood levels 171-222 ng/ml) with
      multiple sclerosis and initially normal kidney function. The patients
      participated in a randomized double-blind study to assess the efficacy of CyA in
      multiple sclerosis. An age- and sex-matched control group (n = 39) received
      azathioprine (Aza). Measurements were made at the end of a 2-year treatment
      period. The 1,25(OH)2D3 serum concentrations were not significantly different
      between the two groups, although they were numerically lower in CyA-treated
      patients [median (range), 28.4 pg/ml (7.8-85.9) vs 41.0 pg/ml (9.2-105.1) in Aza
      treated patients]. The 25(OH)D3 levels were comparable in both groups. There was
      no correlation between the 25(OH)D3 and 1,25(OH)2D3 concentrations. The renal
      function in both groups was stable in the last 6 months of the study. At the end
      of the study period, the endogenous creatinine clearance was significantly lower
      in the CyA-treated group (85 +/- 17 ml/min versus 99 +/- 22 in the Aza-treated
      group, P less than 0.05). The carboxyterminal parathyroid hormone (C-PTH) was
      within the normal range in both groups, although CyA-treated patients had
      significantly higher concentrations (P less than 0.01). The urinary excretion of
      mineral ions, cations and protein was similar in both groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1392431
TI  - Acute aortic thrombosis associated with spinal cord infarction in nephrotic
      syndrome.
AB  - Acute aortic thrombosis associated with spinal cord infarction in a 47-year-old
      man with nephrotic syndrome is described. He was admitted to our hospital
      presenting with the nephrotic syndrome. Renal biopsy revealed mild mesangial
      proliferative glomerulonephritis. The urinary protein excretion rate transiently
      decreased after the start of treatment with prednisolone, but it increased again
      and was followed by the development of the signs and symptoms of spinal cord
      infarction, which was diagnosed by magnetic resonance signal abnormalities, and
      then symptoms of ischemia in the lower limbs. Digital subtraction angiography
      revealed an obstruction at the bifurcation of the abdominal aorta. Emergency
      thrombectomy was performed, and the arterial blood flow was reestablished.
      Laboratory data on the fibrinocoagulation system showed a hypercoagulable state.
      In this case, fibrinocoagulation abnormalities due to the nephrotic syndrome led
      to the hypercoagulable state, and dehydration might have triggered the thrombotic
      complication.

PMID- 1392430
TI  - Estimation of extracellular space and blood volume using bioelectrical impedance
      measurements.
AB  - The bromide-82 dilution space (extracellular space, ECS) and blood volume (BV)
      were measured in 21 patients with esophageal and gastric cancer and in 27
      patients 18-96 months after total gastrectomy. Resistance (R) and reactance (Xc)
      from bioelectrical impedance measurements were used to obtain multiple regression
      equations for ECS and BV. The variables weight, gender, and height 2/Xc were
      independent predictors of ECS (r = 0.767; P less than 0.0001). Height 2/R and
      gender were predictors of blood volume (r = 0.856; P less than 0.0001). The mean
      difference between the Br space and the ECS predicted from impedance measurements
      was 0 +/- 1.54 (mean +/- SD). The limits of agreement (+/- 2 SD) were therefore
      +/- 3.08 l or 19.6% of the mean Br space of 15.7 l. The limits of agreement for
      BV were +/- 789 ml or +/- 19.7% of the average BV of 4008 ml. It is concluded
      that bioelectrical impedance plethysmography using a single frequency can be used
      for the estimation of ECS and BV. The wide limits of agreement, however, may
      limit its used in clinical practice.

PMID- 1392432
TI  - Response to therapy of a type III hyperlipoproteinemic subject with the rare
      apolipoprotein E1 (Gly127----Asp, Arg158----Cys) variant.
AB  - In a preceding paper, we described the molecular biological defects in a patient
      with a severe form of the familial lipoprotein disorder type III
      hyperlipoproteinemia (HLP) and an unusual apolipoprotein (apo) E1 phenotype and
      epsilon 1/"null" genotype. The index case was a 60-year-old white male of German
      ancestry who suffered from a myocardial infarction at age 50 years. He had
      distinctly elevated levels of plasma lipids (triglycerides 551 mg/dl and
      cholesterol 747 mg/dl, respectively) and typical clinical signs of this inborn
      error of lipoprotein metabolism. His mutant apo E1 was shown to be identical to a
      rare (already described) apo E1 (Gly127----Asp, Arg158----Cys) variant. A second
      independent defect at the molecular level was a nucleotide deletion of a
      guanosine (G) in the codon for amino acid 31 of the proband's apo epsilon 3
      allele. This single base deletion (not described before) changed his apo epsilon
      3 allele to a nonfunctional "null" allele devoid of a stable gene product. Here
      we describe the response to combined dietary and medical treatment of the patient
      with this unusual form of type III HLP. His response to therapy was excellent,
      similar to patients with "classical" type III HLP and homozygosity for apo E2.
      However, the correct diagnosis of this familial lipoprotein disorder seems to be
      necessary, even in patients without the expected apo E2/2 phenotype, in terms of
      the prompt and beneficial response to therapeutic interventions.

PMID- 1392434
TI  - Desmopressin reduces night urine volume in geriatric patients: implication for
      treatment of the nocturnal incontinence.

PMID- 1392433
TI  - Blood glycogen content in pregnant women.

PMID- 1392435
TI  - Indocyanine green clearance and duplex sonography in hepatic blood flow.

PMID- 1392436
TI  - The pharmacokinetics of two different concentrations of short-acting insulin,
      intermediate-acting insulin, and an insulin mixture following subcutaneous
      injection.
AB  - To compare the pharmacokinetics of two different concentrations, containing
      either 40 or 100 IU/ml of short-acting human insulin (Velasulin HM), intermediate
      acting human insulin (Insulatard HM), or an insulin mixture (25% short-acting
      insulin, 75% intermediate-acting insulin; Mixtard HM), three randomized, single
      blind, crossover trials were performed using the euglycemic clamp technique.
      Eighteen healthy volunteers received insulin of either formulation subcutaneously
      in each of the studies (15 IU Velasulin, 20 IU Insulatard, or Mixtard). The blood
      glucose levels were maintained constant by glucose infusions. In the trial using
      Velasulin, the two different insulin concentrations were equivalent regarding the
      total absorption [area under the curve (AUC) of serum insulin: 126 +/- 28 and 123
      +/- 35 mU/l x 12 h for U40 and U100 (mean +/- SD)], but not in regard to the rate
      of absorption (t max 1.3 +/- 0.4 and 2.4 +/- 1.0 h for U40 and U100). In the case
      of Insulatard, total absorption was not equivalent (AUC 153 +/- 35 and 128 +/- 37
      ml/l x 24 h for U40 and U100), but the rate of absorption was equivalent (t max
      4.8 +/- 2.9 and 5.3 +/- 4.6 h). In the Mixtard series, total absorption was
      equivalent (AUC 142 +/- 32 and 128 +/- 22 mU/l x 24 h), but the rate of
      absorption was not (t max 2.2 +/- 0.9 and 3.2 +/- 4.2 h for U40 and U100). The
      glucose requirement was not equivalent in each of the three series.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1392437
TI  - Pathogenesis and consequences of Plummer-Vinson syndrome.

PMID- 1392438
TI  - Fibrinolytic mechanisms in tumor growth and spreading.
AB  - The high prevalence of hypercoagulative states in cancer patients has been known
      for more than a century. Venous thrombosis in gastric cancer was described by
      Trousseau in 1865 [55]. In 1878, Billroth observed intravascular thrombus
      formation in association with metastasis [4]. Thrombohemorrhagic complications
      regularly occur in patients with disseminated malignancy and are related to an
      increase in fibrinogen and fibrin turnover. During the past decade, clinicians
      have witnessed considerable advances in the understanding of fibrinolysis.
      Initially centered on the role as part of a dynamic, hemostatic balance, research
      began to unravel the pathophysiological contribution of fibrinolysis to tumor
      progression. The mechanisms of tumor invasion and metastasis formation in cancer
      are of critical importance, since metastasis is the major cause of treatment
      failure and death. It has been suggested that cell-associated proteolytic enzymes
      contribute to tumor aggressiveness [11, 22, 23]. Fibrinolytic mechanisms are
      involved in a number of physiological processes in which tissue degradation and
      remodeling occurs. These include disruption of the ovarian follicle during
      ovulation and blastocyst implantation. These events in part resemble the invasive
      growth of cancer [37, 47]. Inspired by this hypothesis, the role of fibrinolytic
      processes in tumor invasion is under intensive study.

PMID- 1392440
TI  - Behavior of lymphocyte subsets and expression of activation markers in response
      to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer
      patients.
AB  - Cellular aspects of the immunomodulating activity of the galactoside-specific
      lectin from mistletoe (ML-1) were investigated in 10 cancer patients. Regular
      subcutaneous injections (4 weeks) of the optimal dosis of ML-1 (1 ng per kg body
      weight, twice a week) yielded notable increases in the apparent numbers of
      certain lymphocyte subsets [pan T cells; helper T cells; natural killer (NK)
      cells] which are generally believed to be involved in antitumor immunity.
      Moreover, ML-1 administration resulted in an increased level of expression of
      interleukin (IL)2 receptors on lymphatic cells, an indicator of cellular
      activation. In vitro, the exposure of human lymphocytes to ML-1 resulted in an
      enhanced expression of receptors for IL-2 (T cells) and HLA-DQ (B cells), which
      similarly substantiated the capacity of ML-1 to affect immunological parameters
      within the host defense system. Thorough clinical trials are now required to
      assess any impact of the application of the lectin on the course of the disease.

PMID- 1392441
TI  - Association between serum-soluble CD8 levels and parameters of immune activation
      in patients with human immunodeficiency virus infection.
AB  - We compared the serum concentrations of soluble CD8 with the immune activation
      markers neopterin, interferon-gamma, tumour necrosis factor-alpha, soluble CD4,
      and with CD4+ and CD8+ T-cell counts in patients with human immunodeficiency
      virus (HIV) infection. The majority of patients had increased concentrations of
      soluble CD8, interferon-gamma and neopterin, and various significant correlations
      existed between them. Our results support the view that enhanced soluble CD8
      levels indicate activated CD8+ T cells in patients with HIV infection.

PMID- 1392442
TI  - Expansion of neopterin and beta 2-microglobulin in cerebrospinal fluid reaches
      maximum levels early and late in the course of human immunodeficiency virus
      infection.
AB  - Elevated cerebrospinal fluid (CSF) levels of neopterin and beta 2-microglobulin
      (beta 2MG) reflect activation of the cellular immune response in the central
      nervous system (CNS). In 118 consecutive subjects [15 controls and 103 patients
      with human immunodeficiency virus (HIV) infection classified according to the
      Walter Reed staging system (WR)], neopterin and beta 2MG were determined in
      paired samples of CSF and serum. The permeability of the blood-CSF barrier and
      local release of neopterin and beta 2MG were taken into account: The molecular
      weight and diameter were used to determine filtration at the blood-CSF barrier.
      CSF neopterin levels were increased in all stages of HIV infection. beta 2MG
      levels were elevated in WR2 and later stages. Neopterin, beta 2MG, and cell
      counts similarly showed peaks in WR2, as did neopterin and beta 2MG also in the
      later stages WR5 and WR6. Neurologically asymptomatic patients exhibited higher
      neopterin CSF levels than did controls (12.67 +/- 11.6 vs. 2.34 +/- 1.05 nmol/l,
      P less than 0.001) and higher CSF beta 2MG (2.12 +/- 1.25 vs. 1.3 +/- 0.37 mg/l,
      P = 0.001). Patients with HIV encephalopathy had higher levels of beta 2MG (3.75
      +/- 1.83 mg/l) than asymptomatic patients (P less than 0.01). CSF levels of
      neopterin were markedly different in patients with HIV encephalopathy and
      toxoplasmosis (P less than 0.01). A high quantity of local release of the markers
      neopterin and beta 2MG may reflect HIV infection of the CNS in early and late
      stages and additional release upon opportunistic infections.

PMID- 1392443
TI  - Cardiac involvement during and after malaria.
AB  - In 22 patients without a previous history of cardiac disease, we prospectively
      evaluated cardiac involvement during acute malaria and 9 +/- 5 months after
      recovery using non-invasive methods including resting electrocardiogram (ECG) and
      two-dimensional (2D) echocardiography. During the acute phase ECG abnormalities
      were common (5/22); pericardial effusion was found in 2 patients and global left
      ventricular hypokinesia in 1 patient infected with Plasmodium falciparum. At a
      follow-up of 19 patients, the resting ECG and echocardiography were normal or had
      normalized in all patients. The results of our study suggest that persistent
      cardiac damage following malarial infection seems to be rare; however, further
      trials in a larger patient population are needed to confirm our findings.

PMID- 1392439
TI  - The surfactant system of the adult lung: physiology and clinical perspectives.
AB  - Pulmonary surfactant is synthesized and secreted by alveolar type II cells and
      constitutes an important component of the alveolar lining fluid. It comprises a
      unique mixture of phospholipids and surfactant-specific proteins. More than 30
      years after its first biochemical characterization, knowledge of the composition
      and functions of the surfactant complex has grown considerably. Its classically
      known role is to decrease surface tension in alveolar air spaces to a degree that
      facilitates adequate ventilation of the peripheral lung. More recently, other
      important surfactant functions have come into view. Probably most notable among
      these, surfactant has been demonstrated to enhance local pulmonary defense
      mechanisms and to modulate immune responses in the alveolar milieu. These
      findings have prompted interest in the role and the possible alterations of the
      surfactant system in a variety of lung diseases and in environmental impacts on
      the lung. However, only a limited number of studies investigating surfactant
      changes in human lung disease have hitherto been published. Preliminary results
      suggest that surfactant analyses, e.g., from bronchoalveolar lavage fluids, may
      reveal quantitative and qualitative abnormalities of the surfactant system in
      human lung disorders. It is hypothesized that in the future, surfactant studies
      may become one of our clinical tools to evaluate the activity and severity of
      peripheral lung diseases. In certain disorders they may also gain diagnostic
      significance. Further clinical studies will be necessary to investigate the
      potential therapeutic benefits of surfactant substitution and the usefulness of
      pharmacologic manipulation of the secretory activity of alveolar type II cells in
      pulmonary medicine.

PMID- 1392444
TI  - Urodilatin: a new peptide with beneficial effects in the postoperative therapy of
      cardiac transplant recipients.
AB  - Renal failure after heart transplantation (HTx) still remains a serious problem,
      especially when cyclosporin A is used for immunosuppression in the early
      postoperative therapy. To preserve good renal function without reducing
      immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95
      126) in a long-term, low-dose infusion in addition to the usual medication after
      heart transplantation. From November 1990 to June 1991, 51 patients (46 male and
      5 female; mean age 48 years) were treated with a 6-20 ng/kg bw.min infusion for
      96 h after HTx. The renal function and hemodynamic parameters of these urodilatin
      treated patients were compared in this sequential study with 40 patients (33 male
      and 7 female; mean age 49 years) who had undergone HTx previously from May to
      November, 1990, as controls. In this phase IIa study, both groups did not differ
      significantly with respect to age, sex, indication for HTx, and preoperative
      renal function. In comparison with controls patients treated with urodilatin had
      a significantly better renal function: a reduction in the peak plasma creatinine
      (PC values day 4: 1.5 +/- 0.11 vs. 2.19 +/- 0.19 mg/dl; P = 0.002), a lower peak
      serum urea (SU values day 4: 109 +/- 8 vs. 154.7 +/- 8.94 mg/dl; P = 0.0036), and
      a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis
      was maintained in spite of the reduction of furosemide by more than 60% (P =
      0.005) on each day of urodilatin infusion in comparison with controls.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1392445
TI  - Elevated lipoprotein(a) levels in patients with acute myeloblastic leukaemia
      decrease after successful chemotherapeutic treatment.
AB  - Twenty-two patients with acute myeloblastic leukaemia (AML) were studied to
      investigate disease-associated changes in lipid metabolism. Lipoprotein (a)
      [Lp(a)] levels were found to be elevated at the time of diagnosis (median 23
      mg/dl; 41% of patient group had levels greater than 25 mg/dl) and diminished
      after successful chemotherapeutic treatment in 9 of 10 cases, with a maximum
      decrease from 56 to 10 mg/dl. In contrast, reduced levels of total cholesterol,
      low density lipoprotein (LDL) and high density lipoprotein (HDL) (medians 137, 87
      and 20 mg/dl, respectively) were observed at the time of diagnosis. Cholesterol
      and HDL levels increased in all 10 and LDL in 9 cases in which complete remission
      was achieved. These data suggest that the catabolism of LDL-cholesterol might be
      even more enhanced than assumed to date. Furthermore, it indicates that the Lp(a)
      level in acute myeloblastic leukaemia is influenced either directly or indirectly
      by the leukaemic blasts.

PMID- 1392446
TI  - Subacute effects of thiazide administration on renal hemodynamics and calcium
      metabolism.
AB  - To elucidate the renal effects of thiazides as a function of sodium intake, 8
      healthy volunteers without renal disease were studied at baseline and 1 day as
      well as 4 days after the administration of 100 mg hydrochlorothiazide/day. The
      subjects were compared on two different dietary sodium intakes (120 mmol/day and
      220 mmol/day). Measurements comprised inulin clearance (Cin) and
      paraaminohippurate clearance (Cpah) by infusion clearance technique, total and
      ionised calcium, immunoreactive parathyroid hormone (1.84 iPTH), 1.25 (OH)2
      vitamin D3, and indices of hemoconcentration. Acute administration of
      hydrochlorothiazide (HCTZ) caused no change in Cin (before 111 +/- 3 ml/min 1.73
      m2; 24 h after, 107 +/- 2 ml/min 1.73 m2) or Cpah (before, 579 +/- 9 ml/min 1.73
      m2; after, 584 +/- 12 ml/min 1.73 m2), while a significant (P less than 0.01)
      decrease was noted on the 4th day after 100 mg HCTZ/day and normal sodium intake.
      No significant change of creatinine clearance (Ccr) was seen with either
      manouever. Renal hemodynamic changes after HCTZ administration were marginal when
      hemoconcentration was prevented by a high salt intake. Acute administration (1 h)
      of HCTZ caused suppression of 1.84 iPTH (before, 2.3 +/- 0.5 pmol/l; after, 1.9
      +/- 0.2 pmol/l; P less than 0.01), but after 4 days a lower ionised calcium
      (baseline, 1.25 +/- 0.01 mmol/l; day 5, 1.20 +/- 0.02 mmol/l; P less than 0.01)
      was noticed in parallel with hemoconcentration, metabolic alkalosis, and reduced
      1.25 (OH)2 vitamin D3 concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392447
TI  - Renal potassium bicarbonate release in humans exposed to an acute volume load.
AB  - Cells of the renal medulla regulate their volume by transmembrane ion movements
      when exposed to large changes in osmolality. Since renal cells in culture release
      KHCO3 in response to hypotonic stress [11], we investigated the effect of an
      acute water load on urinary KHCO3 excretion in 5 healthy individuals. Water
      diuresis was induced by the ingestion of 1.5 l hypoosmolal fluid (22 mosm/kg H2O)
      over 15 min. The rate of urinary volume excretion increased from an initial value
      of 1.4 ml/min to 9.3 ml/min after 75 min. Urinary osmolality dropped from an
      initial value of 940 +/- 32 mosm/kg H2O to 74 +/- 4 mosm/kg H2O (n = 5). The
      decrease of osmolality was accompanied by the transient release of potassium and
      bicarbonate. Peak values of KHCO3 excretion were observed between 30 and 45 min
      after the onset of the experiment corresponding to the drop of urinary
      osmolality. The magnitude of renal potassium release correlated significantly (r
      = 0.93; P less than 0.05) with endogenous plasma aldosterone concentrations
      measured prior to the experiment in the 5 volunteers. We conclude that medullary
      epithelial cells release KHCO3 when exposed to hypotonic stress. The volume
      regulatory response is upregulated by aldosterone.

PMID- 1392448
TI  - Mesna side effects which imitate vasculitis.
AB  - Mesna (sodium-2-mercaptoethansulfonate) is used in the prophylaxis of
      cyclophosphamide (CYC)-induced hemorrhagic cystitis. Four patients being treated
      with "low dose" CYC and prednisone for vasculitis developed severe side effects
      to Mesna. Fever, arthralgia, myalgia, tachycardia, electrocardiogram changes
      consistent with perimyocarditis, erythroderma, bullous skin and mucous membrane
      lesions, and abdominal complaints with profuse diarrhea were noted approximately
      3 weeks after the initiation of therapy for CYC-induced leukopenia and a
      conservatively reduced prednisone dosage. Positive reexposure tests confirmed the
      association to Mesna use, and hypersensitivity skin tests demonstrated a delayed
      hypersensitivity reaction.

PMID- 1392449
TI  - Endoscopic Doppler sonography in gastroduodenal ulcer bleeding.

PMID- 1392450
TI  - Synovial characteristics of seronegative spondarthritides.

PMID- 1392451
TI  - Concentration of glycogen in blood of diabetics.

PMID- 1392452
TI  - The metabolism of tramadol by human liver microsomes.
AB  - The metabolism of tramadol was investigated in vitro using microsomal fractions
      of human liver. The parent compound and its main metabolites were determined by a
      newly developed high performance liquid chromatography assay. O-demethylation of
      tramadol was found to be stereoselective. The Vmax of the O-demethylation of (-)
      tramadol was 210 pmol.mg-1.min-1, whereas (+)-tramadol was O-demethylated with a
      Vmax of 125 pmol.mg-1.min-1. The Km for both enantiomers was determined to be 210
      microM. O-demethylation was inhibited competitively by quinidine (ki = 15 nM) and
      propafenone (ki = 34 nM). N-demethylation was also stereoselective,
      preferentially metabolizing the (+)-enantiomer. Whereas O-demethylation displayed
      monophasic Michaelis-Menten kinetics, N-demethylation was best described by a two
      site model. Competitive inhibition of the O-demethylation both by quinidine and
      propafenone suggests that O-demethylation is carried out by P-450IID6.

PMID- 1392454
TI  - Screening of prostatic carcinoma: a critical analysis. The problem of screening
      and early diagnosis. Munich, 19-21 March 1992.

PMID- 1392455
TI  - Measuring patient anxiety in coronary care. Part 1.
AB  - Patient anxiety is a common problem identified by nurses. However, the difficulty
      of assessing the level and significance of the anxiety is problematic. This paper
      discusses the issue of measuring patient anxiety, specifically in Coronary Care.
      As well as discussing physiological measures, three appropriate psychometric
      instruments are identified (the State-Trait Anxiety Inventory--STAI; the Hospital
      Anxiety and Depression Scale--HAD; a Linear Analogue Anxiety Scale--LAAS), along
      with a review of the relevant literature. Systematic anxiety measurement, and
      management of maladaptive anxiety would appear to be appropriate and meaningful
      nursing functions within the provision of holistic patient care in Coronary Care.

PMID- 1392453
TI  - Long-term effect of lovastatin alone and in combination with cholestyramine on
      lipoprotein (a) level in familial hypercholesterolemic subjects.
AB  - We have determined the effect of lovastatin alone or in combination with
      cholestyramine on lipoprotein (a) [Lp(a)] levels in 59 heterozygotes for familial
      hypercholesterolemia (FH) treated for 33.8 (+/- 6.1) months. The median pretrial
      Lp(a) value was 10.2 mg/100 ml, which is twice the median value in healthy people
      examined at the Institute of Medical Genetics, University of Oslo. The median
      Lp(a) level was insignificantly reduced by 10.3% during the first 20 weeks when
      the subjects were on a standardized medication of increasing doses of lovastatin
      and cholestyramine. The first 20 weeks were followed by usual care treatment
      period, and a further decrease in Lp(a) level to 16.2% (P = 0.0012) was observed
      at the end of the study. Comparison between the 20 subjects on lovastatin
      monotherapy and the 31 subjects on the combined therapy of lovastatin and
      cholestyramine, revealed that the subjects on monotherapy had a median reduction
      of 20.1%, and the subjects on the combined therapy had a reduction of 15.4%.
      Thus, it appears that the reduction in Lp(a) level could be ascribed to
      lovastatin alone.

PMID- 1392456
TI  - Objectives of the CACCN.

PMID- 1392457
TI  - The high cost of critical care.

PMID- 1392458
TI  - A positive step.

PMID- 1392459
TI  - The new co-operative research centre for cardiac technology: significance for
      nurses.

PMID- 1392460
TI  - A recent reminder of botulism.
AB  - Botulism is a rare yet potentially common form of food poisoning that can be
      fatal. (1) Few documented cases of botulism exist in Australia (2,3,4) and New
      Zealand (5), emphasising how infrequently it is encountered. The recent admission
      to our Intensive Care Unit (ICU) of a man suspected of having botulism was a
      timely reminder of just how dangerous this condition can be. This paper will
      review the contemporary knowledge and interventions necessary in the management
      of botulism. It will also utilise anecdotes from our recent experience to
      illustrate some of the clinical scenarios and potentially fatal complications
      seen in this condition.

PMID- 1392461
TI  - Development of the nurse practitioner.
AB  - In the first of two articles on the development of the emergency nurse
      practitioner, Peter Howie reports on a new scheme in Lincoln where all first
      level nurses have been trained as nurse practitioners. The initiative was
      introduced following a study in the theoretical management of patients by
      experienced accident and emergency sisters. The author outlines the training
      course provided and the protocols within which nurse practitioners work.

PMID- 1392462
TI  - Emergency nurse practitioners.

PMID- 1392463
TI  - Another editorial asking us to embrace change.

PMID- 1392464
TI  - Just another death?

PMID- 1392465
TI  - 'Inappropriate attender' in A&E.
AB  - With the current emphasis on reducing patient waiting times, accident and
      emergency nurses may be tempted to close the doors on what they consider to be
      'inappropriate attenders'. The author warns that public perceptions of A&E are
      often at odds with the nurses view, and that all patients should have access to
      accident and emergency services. This article takes a critical look at triage
      since its inception as a means of assessing wounded soldiers during the first
      world war. He explores patient assessment in accident and emergency departments
      and nurses' attitudes towards the 'inappropriate attender', highlighting the need
      for caution when dealing with enquiries from the general public.

PMID- 1392466
TI  - Influence of chromium on some physiological variables of Anabaena doliolum:
      interaction with metabolic inhibitors.
AB  - The impact of 2,4-dinitrophenol and chlorophenyl dimethylurea on ATP content,
      carbon fixation, O2 evolution, nitrogenase activity and Cr uptake of Anabaena
      doliolum has been studied. 2,4-Dinitrophenol has been found to be more toxic than
      chlorophenyldimethylurea for all these processes. However, when Cr toxicity to
      above variables was assessed in their presence the interaction was less than
      additive. An initial (10-15 min) concentration-dependent rapid Cr uptake,
      followed by a slow one, indicates a biphasic uptake. A significant inhibition of
      Cr uptake in the presence of both these metabolic inhibitors suggests the
      involvement of metabolic processes in Cr uptake.

PMID- 1392467
TI  - Increased urinary excretion of zinc and copper by mercuric chloride injection in
      rats.
AB  - The effects of HgCl2 on urinary excretion of Zn, Cu and metallothionein at
      different time intervals were observed in male Wistar rats. The rats were given a
      daily intraperitoneal injection of 203HgCl2 (0.5 or 1.0 mg Hg kg-1) for 2 days.
      203Hg, Zn, Cu and metallothionein in urine, kidney and liver were analyzed.
      Significant increases in urinary Zn and Cu concentrations were found in HgCl2
      dosed groups. Elevated urinary Zn and Cu concentrations were accompanied by an
      increased metallothionein excretion in urine at different time periods. Zn
      concentration in urine remained elevated during the entire observation period of
      7 days. There were also increased concentrations of Cu and Zn in the renal cortex
      in one of the two exposed groups. The results indicate that urinary Cu and Zn are
      related to the manifestation of renal toxicity and/or the synthesis of
      metallothionein in kidney induced by mercury.

PMID- 1392468
TI  - Antifeeding and insect-growth-regulating activity of certain metal complexes
      towards Spodoptera litura; F.
AB  - Metal complexes of divalent cobalt, nickel and copper and trivalent iron were
      synthesized using N-salicylidene-3-aminocoumarin as chelating agent. The ligand
      behaves as a monobasic ONO donor towards Co(II), Ni(II) and Cu(II) and as an ON
      as well as an ONO donor towards Fe(III). All the complexes have been proposed to
      have octahedral geometry on the basis of analytical, thermal conductivity,
      spectral and magnetic data. The complexes have been screened against Spodoptera
      litura; F (Lepidoptera: noctuiidae) for antifeeding and insect-growth-regulating
      activity. The results show appreciable insect-growth-regulating activity
      associated with metal complexation.

PMID- 1392469
TI  - Iron(III) complexes of chrysobactin, the siderophore of Erwinia chrysanthemi.
AB  - The phytopathogenic bacterium Erwinia chrysanthemi produces the monocatecholate
      siderophore chrysobactin under conditions of iron deprivation. Only the
      catecholate hydroxyl groups participate in metal coordination, and chrysobactin
      is therefore unable to provide full 1:1 coordination of Fe(III). The
      stoichiometry in aqueous solution is a variable dependent on pH and metal/ligand
      ratio, in addition to being concentration dependent. At neutral pH and
      concentrations of about 0.1 mM, ferric chrysobactin exists as a mixture of bis
      and tris complexes. Chrysobactin and its isomers form optically active tris
      complexes. The dominant configuration depends on the chirality of the amino acid
      to which the catecholate moiety is attached.

PMID- 1392470
TI  - Structure and function of vanadium compounds in living organisms.
AB  - Vanadium has been recognized as a metal of biological importance only recently.
      In this mini-review, its main functions uncovered during the past few years are
      addressed. These encompass (i) the regulation of phosphate metabolizing enzymes
      (which is exemplified for the inhibition of ribonucleases by vanadate), (ii) the
      halogenation of organic compounds by vanadate-dependent non-heme peroxidases from
      seaweeds, (iii) the reductive protonation of nitrogen (nitrogen fixation) by
      alternative, i.e. vanadium-containing, nitrogenases from N2-fixing bacteria, (iv)
      vanadium sequestering by sea squirts (ascidians), and (v) amavadine, a low
      molecular weight complex of V(IV) accumulated in the fly agaric and related
      toadstools. The function of vanadium, while still illusive in ascidians and
      toadstools, begins to be understood in vanadium-enzyme interaction.
      Investigations into the structure and function of model compounds play an
      increasingly important role in elucidating the biological significance of
      vanadium.

PMID- 1392472
TI  - Comparison of the clastogenic effects of antimony trioxide on mice in vivo
      following acute and chronic exposure.
AB  - Antimony trioxide (Sb2O3), in aqueous suspension, was administered by gavaging to
      mice and monitored for chromosomal aberrations in bone marrow and sperm head
      abnormalities in germ cells. Acute exposure to the doses followed by observations
      after 6, 12, 18 and 24 h did not show any clastogenic effects. Chronic exposure
      daily to different doses for periods up to 21 days induced chromosomal
      aberrations in bone marrow. The frequencies were dose-dependent to a significant
      extent but no relationship could be seen with the sex of the animal. The findings
      indicate the harmful effects of cumulative exposure for prolonged periods to
      Sb2O3, which is being increasingly used in various industries.

PMID- 1392471
TI  - Identification of the ferrioxamine B receptor, FoxB, in Escherichia coli K12.
AB  - The photoreactive p-azidobenzoyl analog of ferrioxamine B was used to show that
      ferrioxamine-B-mediated iron transport is separate and distinct from coprogen
      mediated iron transport in Escherichia coli. Photolysis of this analog inhibited
      uptake of [59Fe]ferrioxamine B but not [59Fe]ferrichrome. Conversely, photolysis
      of the p-azidobenzoyl analog of coprogen B inhibited uptake of [59Fe]coprogen but
      not [59Fe]ferrioxamine B or [59Fe]ferrichrome. Photolabeling of outer membranes
      with p-azidobenzoyl-[59Fe]ferrioxamine B resulted in the labeling of two iron
      regulated peptides with molecular masses of about 66 and 26 kDa. Expression of
      these peptides was increased when ferrioxamine B was the sole iron source. Both
      peptides were present in outer membrane preparations of the fhuF mutant H1717,
      but the 66 kDa peptide was not inducible. These results are evidence for an outer
      membrane receptor in E. coli unique for linear ferrioxamines.

PMID- 1392474
TI  - [Analysis of the correlations between immunological changes and syndrome groups
      in patients with immunological thrombocytopenic purpura (ITP)].
AB  - To study the relationship between the immunological changes and syndrome (Zheng,)
      groups by TCM of ITP, the T-lymphocyte subsets, B-lymphocyte, NK cell, platelet
      associated IgG (PAIgG, PAIgA, PAIgM) and antiplatelet-autoantibodies (GPIIb,
      GPIIIa, GP I b) of 66 patients with ITP were assisted using APAAP and ELISA
      method separately. It was found that the T-lymphocyte subsets, PAIg and syndrome
      groups of ITP were closely related. From the group of blood-heat (Xuerewangxing)
      to the group of deficiency of both Qi and blood, the group of asthenia of both
      Spleen and Kidney, the group of deficiency of Liver-yin and Kidney-yin, and the
      group of deficiency Yin and Yang Ts lymphocyte successfully increased (from 29. 0
      +/- 8.0% to 47.2 +/- 10.0%), Th/Ts ratio declined (from 1.35 +/- 0.60% to 0.69 +/
      10%), PAIg increased gradually except for PAIgM,PAIgG of the group of deficiency
      Yin and Yang. Only the Th of the group of asthenia of both Spleen and Kidney
      among 5 syndrome groups was decreased significantly and contrary to the group of
      deficiency of Liver-Yin and Kidney-Yin. These results indicated that every
      syndrome group has specific characteristics, and immunological changes of ITP
      could have prognostic value.

PMID- 1392475
TI  - [Effects of Cordyceps sinensis (CS) on in vitro natural killer cells].
AB  - The effect of Cordyceps sinensis (CS) on peripheral NK cells from healthy persons
      and leukemia patients were studied. The results showed that CS could argument the
      NK cell activity, meanwhile, the dose-dependent effect was found within the range
      of dosage adopted (r = 0.984, P less than 0.01; r = 0.988, P less than 0.01).
      Furthermore, CS could also improve the CD16 marker expression on lymphocytes and
      the binding capacity to K562 cells. Cytotoxicity could not present when the PBNCs
      were co-incubated with CS. These results suggested that CS could be exploited and
      utilized as an approach of biological responsive modifier therapy (BRMT) in the
      treatment of leukemia.

PMID- 1392473
TI  - Novel heme-binding component in the serum of the channel catfish (Ictalurus
      punctatus).
AB  - The serum of the channel catfish (Ictalurus punctatus) was examined for heme- and
      hemoglobin-binding proteins. Electrophoretic mobility retardation assays failed
      to detect a hemoglobin-binding material similar to mammalian haptoglobin;
      however, a heme-binding component (not previously described) was identified in
      catfish serum. The heme-binding component was purified by gel filtration
      chromatography; electrophoretic analyses suggested it to be composed of two
      polypeptide subunits of molecular masses about 115 and 98 kDa. This composition
      is inconsistent with hemopexin, the known heme-binding serum protein of mammals.
      Although it was not fully saturated with heme, the catfish component contained
      detectable heme in normal sera. When complexed by the binding material, heme was
      used as an iron source by isolates of the bacterial Gram-negative genus
      Aeromonas; the capacity of other bacteria to use the complex was not tested. The
      physiological function of the catfish heme-binding serum protein is presently not
      clear.

PMID- 1392476
TI  - [Preliminary study on the treatment of diabetic retinopathy utilizing with
      nourishing yin, tonifying kidney and blood-activating herbs].
AB  - 23 cases including 45 eyes of diabetic retinopathy treated with nourishing Yin,
      tonifying Kidney and blood-activating herbs were presented. The results showed
      that the serum viscosity and cholesterol were markedly decreased (P less than
      0.01), and the implicit times of a-wave and b-wave in flash electroretinogram(F
      ERG) were significantly advanced than those of themselves before treatment (P
      less than 0.01 and P less than 0.05 respectively). The visual acuity in most
      cases was improved and the effective rate was 64.44%. The therapeutical mechanism
      for diabetic retinopathy used by nourishing Yin, tonifying Kidney and blood
      activating herbs were discussed. The authors suggested that the Chinese herbs
      probably could change the chemical and physical properties of blood, promote the
      ocular circulation and the absorption of sludged blood and decrease the retinal
      ischemia.

PMID- 1392477
TI  - [Correlation between syndrome types of traditional Chinese medicine and
      peripheral T lymphocytes subsets in Graves' disease].
AB  - This paper reports the determined results of OKT3, OKT4, OKT8, ERFC, smIg and
      CIC, TMCA, TGA in 31 cases of Graves disease and in 20 normal controls. The
      results showed that the OKT3, OKT4, OKT8, ERFC were significantly lower than
      those in the normal controls, whereas the smIg was higher than that in normal
      controls. The difference between the two groups was very significant. Even though
      the ratio of OKT4/OKT8 showed no significance of both. Typology of Graves disease
      according to the theory of TCM, all 31 cases were divided into two types: (1) 14
      cases of depression of Liver-energy and asthenia of Spleen; (2) 17 cases of
      deficiency of yin leads to hyperactivity of Fire. The OKT8 and the ratio of
      OKT4/OKT8 in the latter respectively were lower and higher than those of the
      former. The difference between the two types was significant (P less than 0.01, P
      less than 0.05) whereas the positive rates of the CIC, TMCA, TGA also were higher
      in the deficiency of Yin leads to hyperactivity of Fire than those in the
      depression of Liver-energy and asthenia of Spleen. After treatment with combined
      TCM-WM on 31 cases of Graves disease, it was found that the OKT4, OKT8, ERFC were
      significantly elevated, the smIg was markedly decreased than those without
      treatment. It was also found that smIg markedly decreased in two types, OKT8,
      ratio of OKT4/OKT8 in the latter and ERFC in both types all returned to normal.
      Remainder indexes had no obvious change before and after treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1392478
TI  - [Qi-xue of traditional Chinese medicine and the electroencephalography energy].
AB  - The experiment observed the different changes of EEG energies among 37 patients
      of neuroasthenic syndrome, 18 patients of anxiety, 28 patients of cerebral
      apoplexy in recovery stage, 48 cases healthy persons, and 13 healthy persons aged
      over 60 years. It was found that the changes in EEG energies coincided with the
      changes in Qi-Xue system. The results showed that analysis of EEG energy could be
      an objective basis for studying Qi-Xue of traditional Chinese Medicine and the
      change of EEG energy could be used in judging the condition of Qi-Xue.

PMID- 1392479
TI  - [Relation between treatment with traditional Chinese medicine for recurrent
      aphthous ulcer and human zinc and copper].
AB  - The purpose of the study is to explore the relation between general condition of
      patients with recurrent aphthous ulcer (RAU) and human zinc and copper with TCM
      conception of the organism as a whole, and adjustment effect of human body zinc
      and copper by TCM treatment. Results showed that the average value of serum zinc
      of 75 cases of RAU was on lower level within normal range, serum copper was
      normal, the rate of copper to zinc was higher than normal value. Analysis using
      the TCM theory showed serum zinc of patients of deficiency symptom-complex was
      lower than excessiveness symptom-complex, the rate of copper to zinc of patients
      of deficiency symptom-complex was higher than normal range. The zinc content of
      serum and the rate of copper to zinc were different in patients of various
      symptom-complexes of RAU. The zinc and copper contents of serum were adjusted,
      the rate of copper to zinc was normalized and the immune function of T-cell
      increased distinctly by TCM treatment according to an overall differentiation of
      symptoms and signs. Thus the therapeutic effect of TCM was better than zinc
      preparation.

PMID- 1392480
TI  - [Research of the relation between the type of asthenia of the spleen and kidney
      and platelet associated antibodies and T-lymphocyte subsets in idiopathic
      thrombocytopenic purpura].
AB  - Idiopathic thrombocytopenic purpura (ITP) is a kind of disease associated with
      immunity. At present a great quantity of study on ITP has been made on humoral
      and cellular immunity. But there are few reports about the relationship between
      the types based on the differential diagnosis of TCM and immune rationale of ITP.
      In order to deeply explore the relationship between the types based on
      differential diagnosis of TCM and immune rationale of ITP., the authors measured
      PAIg and T lymphocyte subsets of 34 ITP patients of asthenia of both Spleen and
      Kidney. The value of PAIgG increased in both types of Spleen failing to control
      blood (SFCB) and deficiency of Spleen-yin and Kidney -yin (DSYKY), and the value
      of PAIgG of the type of DSYKY was significantly higher than that of SFCB (P less
      than 0.01). OKT3, OKT4/OKT8 of the type of SFCB remarkably decreased (P less than
      0.05), OKT4, OKT4/OKT8 of DSYKY also remarkably decreased (P less than 0.001),
      while OKT8 significantly increased (P less than 0.001). The above results
      suggested that the type of DSYKY has more serious immune dysfunction than the
      type of SFCB, and the types of SFCB and DSYKY has close relationship with PAIg T
      lymphocyte subsets.

PMID- 1392481
TI  - [Effect of total saponins of Panax ginseng on hematopoietic progenitor cells in
      normal human and aplastic anemia patients].
AB  - Ginseng was said to be benefit for anemia in TCM. Proliferation effects of total
      saponins of panax ginseng (TSPG) on hematopoietic progenitor cell in normal
      individuals and 29 patients with aplastic anemia (AA) were observed by bone
      marrow culture of BFU-E, CFU-E, CFU-GM in vitro compared with methyltestosterone
      (MT). The results showed that TSPG might prompt proliferation of normal
      progenitor cells at the concentration of 20 micrograms/ml. The number of BFU-E,
      CFU-E and CFU-GM had increased by 37.8 +/- 2.9%, 31.4 +/- 2.9% and 33.3 +/- 4.0%
      over the controls respectively; furthermore TSPG was still useful to BFU-E, CFU-E
      growth without Epo in vitro, although the colony numbers were very lower.
      Otherwise MT was useless to CFU-GM. 14 of the 29 patients with AA who responded
      to MT showed sensitivity to TSPG in marrow culture (the rising rate of colony
      formation exceeded 30%), but immune-mediated AA (patient's PBMNC suppressed
      normal hematopoiesis) and stem cell-decreased AA (few of colony was formed)
      showed almost no expression for TSPG activity because of immunological
      suppression system and absence of progenitors.

PMID- 1392482
TI  - [Study on the granule of shencao fuzheng kangai].
AB  - The clinical effect of the granule of Shencao Fuzheng Kangai had been proved and
      the animal experiment was carried out. The results showed that: (1) No toxic
      response was found in acute toxicity test. (2) The granule could prevent WBC from
      decreasing severely in chemotherapy experiment (P less than 0.01). (3) It was
      indicated that the granule could improve the phagocytic function of macrophage in
      carbon clearance experiment (P less than 0.01). (4) It was meant that the granule
      could inhibit the growing of some solid carcinoma in inoculation experiments.

PMID- 1392484
TI  - [Principles of the positron emission tomography and its application in the
      integration of traditional Chinese medicine and Western medicine].

PMID- 1392485
TI  - [Review and prospect on therapeutic research of hematologic disease with
      traditional Chinese and Western medicine].

PMID- 1392483
TI  - [Preventive and therapeutic effects of hirudo on incipient acute tubular necrosis
      in rats].
AB  - Male Sprague-Dawley rats, weighing 180-250 g and depleted with water for 16 h,
      were injected with glycerol (im) to induce acute tubular necrosis, and then
      divided into groups given blood-activating and stasis-removing drug, Hirudo
      solution (GH) tap water (GW), verapamil (GV) and none (GSDW) in incipient stage
      separately. It was observed that levels of BUN increased at 24th and 48th h after
      administration of glycerol and levels of Bcr increased at 3rd, 24th and 48th h
      after injecting glycerol in GH were significantly lower than those increased in
      GW and GSDW (P less than 0.05-P less than 0.001), but roughly similar to those in
      GV (P greater than 0.05-P greater than 0.5). Renal histopathological damage under
      light microscope and electron-microscope in GH at 3rd and 24th h after
      administration of glycerol were also less severe than those in GW and GSDW. The
      results suggested that Hirudo could exert a preventive and therapeutic effects on
      incipient acute tubular necrosis induced by glycerol in rats.

PMID- 1392486
TI  - [Diagnosis and treatment of idiopathic thrombocytopenic purpura].

PMID- 1392487
TI  - [Current status of research on sort-term turn to the negative of serial
      biological markers in the patients with hepatitis B by traditional Chinese
      medicine].

PMID- 1392488
TI  - [Clinical epidemiological study on risk factors of coronary heart disease in 743
      subjects].
AB  - This paper sums up the clinical epidemiological investigation data on risk
      factors (RF) of coronary heart disease (CHD) among 743 office workers, with an
      average age of 61.0 +/- 8.0. The investigation involved factors relating to
      history, physical examination, biochemistry, blood rheology and TCM Syndrome
      Differentiation. According to the results of the computerized single-factor
      correlation analysis, the incidence of CHD in RF exposed group was obviously
      higher than that of unexposed one, 65 RF such as hypertension, diabetes,
      hyperlipemia, smoking, body weight, HDL-C/TC, blood viscosity etc. were recorded.
      Using multivariate regressive analysis it revealed that hypertension, diabetes,
      total cholesterol, heavy cigarette smoking, overweight, diastolic pressure,
      cortisol, TCM senile index, Blood Stasis Syndrome, Qi Stagnation Syndrome, Qi
      Deficiency Syndrome and Heart Deficiency Syndrome were the main RF. The result
      concerning RF of Western medicine (WM) was in conformity with that at home and
      abroad. In addition, some TCM-RF were selected which couldn't be replaced by WM
      RF. These indicate that there are TCM-RF and WM-RF in the development of CHD and
      it is better to adopt the method for preventing and treating CHD with combined
      TCM-WM. As to TCM-RF of CHD, the authors consider that there are both the factors
      of Deficiency and Excess, so preventing and treating CHD should aim at
      reinforcing the Deficiency and reducing the Excess.

PMID- 1392489
TI  - [Correlation analysis between plasma atrial natriuretic peptide and cardiac
      function in blood deficiency syndrome].
AB  - The function of ANP in the cardiovascular regulation is very similar with the TCM
      theory of "the Heart governs blood circulation". Using the method of cardiac
      impedance to check cardiac output and the method of radioimmunoassay (RIA) to
      check plasma ANP, the result showed that in the status of Blood Deficiency
      Syndrome, cardiac function was impaired, there were reduced kinemia and stroke
      volume, as well as markedly raised plasma ANP and peripheral resistance. The
      above-mentioned indexes were significantly different from those of normal group
      (P < 0.01). Using multivariate regression analysis, cardiac output was negatively
      correlated with the plasma ANP (P < 0.05). 23 cases with Blood Deficiency
      Syndrome showed normal hemoglobin, but an evidently changed cardiac output and
      plasma ANP were closely related with the level of the Blood Deficiency. Both
      parameters might serve as the objective basis to reflect the level of Blood
      Deficiency to facilitate the clinical diagnosis of the patient.

PMID- 1392490
TI  - [Clinical and experimental study on its regulatory function of yi xin decoction
      (heart-nourishing decoction) to lipids metabolic disturbance in coronary heart
      disease].
AB  - In this research, 74 patients with coronary heart disease (CHD) were grouped in
      matched-pair, one group took orally Inositol and Mai Tong as the control group,
      the other group took orally Yi Xin Decoction as the tested group. Indices, i. e.
      serum levels of apolipoprotein A-1 (Apo A-1), apolipoprotein B (Apo-B), high
      density lipoprotein cholesterol (HDL-c), high density lipoprotein subcomponent
      cholesterol (HDL2-c), B-lipoprotein (B-LP), total cholesterol (Tch), triglyceride
      (TG) were measured before and after treatment for 28 days; the results showed
      that the patients with CHD have prominent derangement of lipid metabolism, which
      is similar to previous reports. Yi Xin Decoction modified according to Syndrome
      Differentiation, produced the effect of decreasing the serum Apo-B levels and TG.
      It also increased Apo-A-1, HDL-c and HDL2-c respectively. Moreover the effect of
      lowering Apo-B and raising HDL-c in the Yi Xin Decoction group was better than
      that in the control group. There was no side effect at all; all these indicated
      that Yi Xin Decoction has a remarkable function of regulating the disturbance of
      lipid metabolism in CHD patients. In order to further investigate the curative
      effect of Yi Xin Decoction and elucidate its mechanism, the authors have also
      investigated Yi Xin Decoction on the experimental mice with hyperlipemia. The
      result Showed that Tch and TG in atromid and Yi Xin Decoction group reduced after
      medication, P < 0.01. In comparing with control group, the HDL-c and acidic
      cholesterol in stool Yi Xin Decoction group rose, P < 0.05. The above study has
      provided reliable basis for the clinical application of Yi Xin Decoction and also
      a new medicine to regulate disturbance of lipid metabolism for CHD patients.

PMID- 1392492
TI  - [Effect of qigong on electrocardiographic autopower spectrum function].
AB  - The Changes of positive rate of 17 coronary heart disease cases with frequency
      domain-correlative cardiogram (FCG) > or = 7 grades were evaluated with
      electrocardiographic autopower spectrum function before and after Qigong
      exercise. 17 Qigong-exerciser aged from 54 to 72 (mean 66 year old, male 5,
      female 12) underwent Qigong exercise in 65 to 103 days and were evaluated using
      FCG to compare with pre-Qigong exercise status. The results showed that the
      positive rate of abnormal electrocardiographic autopower spectrum function of
      lead V5 (Gxx 1/2) decreased from 59% (10/17) to 0% (0/17), the lead II (Gyy 1/2)
      from 82% (14/17) to 41% (7/17), P < 0.01 and 0.05. This study suggested that
      Qigong exercise could significantly decrease the positive rate of abnormal
      electrocardiographic autopower spectrum function and improve perfusion of
      coronary artery or cardiac dysfunction produced by myocardial ischemia.

PMID- 1392491
TI  - [Clinical study of qianxining in the treatment of 60 cases of yang hyperactivity
      due to yin deficiency type of hypertension].
AB  - 60 cases with Yang Hyperactivity due to Yin Deficiency type of hypertension were
      randomly divided into two groups. One was treated with TCM and the other with WM
      as control. The results showed that: (1) there were no significant differences in
      the total effective rate and the amplitude of lowering of blood pressure between
      two groups; (2) the improvement of symptoms and disturbance of autonomic nerve
      was significant in TCM group in comparison with control; (3) there were some
      changes in HR, SV, plasma PRA, TXB2 and 6-keto-PGF1 alpha level in both groups,
      but the decrease of TXB2/6-keto-PGF1 alpha ratio was significant in TCM group
      only (P < 0.05); (4) TC and TG in patients with hyperlipemia showed a remarkable
      drop in TCM group (P < 0.02; P < 0.005). All these revealed that Qianxining was a
      satisfactory hypotensive remedy and a further exploration of its mechanism is
      suggested.

PMID- 1392493
TI  - [Preliminary study of rose shu-xin oral liquid in the treatment of angina
      pectoris in coronary heart disease].
AB  - 200 cases with the Qi Stagnation and Blood Stasis type of coronary heart disease
      were divided into two groups randomly. Group A used Rose Shu-Xin (heart
      comforting) oral liquid which is mainly made from the local natural resources
      Rose compound products. While group B used Salvia miltiorrhiza (co.) tablet. The
      results showed that in group A, the total effective rate was 98% and the ECG
      improving rate was 75%, while in group B, it was 50% and 40% respectively. There
      was significant difference between group A and B (P < 0.01). Experiments have
      proved that the Rose oral liquid could improve the myocardial ischemia of the
      experimental rabbit. It could also reduce the size of infarction area, thus
      protected the heart from infarction. No adverse action was found in animal
      experiments and clinical practice. It has proved that the oral liquid could
      dredge the Liver and regulate the flow of Qi, and remove any obstruction to it.
      It could also promote the circulation of Blood and relieve pain. It gave the
      Heart disease a cure from the Liver in TCM theory.

PMID- 1392494
TI  - [Experimental study of atherosclerosis and cholelithiasis with the same
      treatment. I. Effects of yiqi huoxue and shugan liqi agents in atherosclerosis of
      rabbit].
AB  - This paper reports the treatment with Yiqi Huoxue and Shugan Liqi agents in
      atherosclerosis of rabbit. The results suggested: 1. Both decoctions could reduce
      the cholesterol of hypercholesterolemia and improve the atherosclerosis, but the
      former was better than the latter. 2. Both decoctions could alter the components
      of bile lipids, but on the contrary, the latter was better than the former in
      reducing the formation of gallstones. 3. Both decoctions could decrease the
      plasma concentration of LPO and ratio of TXB2/6-K-PGF1 alpha, while increase the
      ratio of cAMP/cGMP in plasma. So, the different prescriptions of TCM affecting
      the same link of pathogenesis might play the role of "Different Treatments in
      Same Disease".

PMID- 1392495
TI  - [The effect of Coptis chinensis on lipid peroxidation and antioxidases activity
      in rats].
AB  - In order to make a systematic study of the effect of Coptis chinensis on free
      radicals, the authors used the method that the drug and the brain homogenate of
      rat were mixed and incubated to investigate the effect of Coptis on lipid
      peroxidation. The result showed that the malondialdehyde (MDA) product of rat
      brain homogenate inhibited by 5% Coptis was significantly different from control
      (P < 0.001). On the basis of the above-mentioned results, the effect of Coptis on
      lipid peroxidation and diabetes of rats induced by alloxan was investigated. The
      result showed: (1) The MDA product of both pancreas and liver homogenate in
      Coptis group was significantly less than that in control and alloxan group (P <
      0.01, P < 0.05). (2) Superoxide dismutases (SODs) in erythrocytes activity was
      the same for all groups (P > 0.50). (3) The blood catalase (CAT) activity in
      alloxan group markedly decreased compared with control group (P < 0.05), but no
      significant change between Coptis and alloxan group (P > 0.05). (4) The value of
      serum glucose in alloxan group was significantly increased in comparing with
      control group (P < 0.05). There was a trend to decrease the value of serum
      glucose in Coptis group compared with alloxan group, but no significant
      difference between two groups (P > 0.05). The experiment indicated that there was
      very strong inhibitory effect of Coptis to the lipid peroxidation in vitro and in
      vivo. Coptis could protect rat from diabetes inducing by alloxan and that
      probably was due to the fact that Coptis was able to inhibit alloxan inducing
      free radicals.

PMID- 1392496
TI  - [Effect of Salvia miltiorrhiza on the cardial ischemia in rats induced by
      ligation].
AB  - I.p. injection (5 g crude drug/kg) of water extract of Salvia miltiorrhiza to
      S.D. rats can prevent the acute cardial ischemia induced by the ligation of the
      coronary artery. The elevation of S-T segment in the electrocardiogram caused by
      the ischemia was greatly reduced in animals treated with Salvia miltiorrhiza
      compared with control group. The ischemia area in the left ventricle was
      significantly reduced and survival rate of the rats increased.

PMID- 1392498
TI  - [Prospect on the soaring revolution of medicine in China].

PMID- 1392497
TI  - [Experimental research on improving the blood flow of ischemic myocardial tissue
      in rabbits by using Panax ginseng].

PMID- 1392499
TI  - [Reviewing and evaluating of the traditional Chinese medicine affecting on
      immunological function].

PMID- 1392500
TI  - [A survey of clinical use and research of xuefu zhuyu decoction].

PMID- 1392501
TI  - Lasers in periodontics.
AB  - Clinical lasers are of two types. Soft lasers are essentially an aid to healing,
      with relatively few rigorous studies available to support their use. Surgical
      hard lasers, however, can cut both hard and soft tissues, replacing the scalpel
      and drill in many areas. After initial experiments with the ruby laser, most
      clinicians have been using argon, carbon dioxide, and now Nd:YAG systems. The
      first dental laser based on a Nd:YAG engine provides handpieces of similar size
      to conventional instrumentation, and being fed by a fibre-optic "cable," has the
      flexibility for intra-oral use that the carbon dioxide lasers, widely used in
      oral surgery, lack. Furthermore, extensive clinical investigation has
      demonstrated their safety in clinical practice, and the fact that procedures can
      usually be performed without a local anaesthetic is obviously seen as an
      advantage by patients. Sterilizing as it cuts, the Nd:YAG laser promises to find
      uses not only in caries removal and soft tissue surgery but also in periodontics
      and endodontics.

PMID- 1392502
TI  - Laser surgery for immunosuppressive gingival hyperplasia.

PMID- 1392503
TI  - An augmented regenerative technique for severe osseous defects.
AB  - Techniques for new attachment using the principle of guided tissue regeneration
      with barrier membranes have become accepted as a method for treating teeth with
      severe osseous defects and furcation involvement. After an evaluation of existing
      membranes and techniques, a procedure was developed using an expanded
      polytetrafluoroethylene soft tissue patch, 1 mm thick (W. L. Gore and Assoc.,
      Flagstaff, AZ), in conjunction with an alloplast hydroxylapatite bone substitute
      (HA-500, 40-60 mesh) (Orthomatrix, Minneapolis, MN), to maintain a space for the
      maturation of the blood clot. An in vitro study of microbial adherence to the
      soft tissue patch indicated that the number of attached Streptococcus sanguis
      (gordonii) G9B, and Actinomyces viscosus T14 (V) cells was significantly lower (P
      < .005 and P < .025, respectively) than the number of bacteria that attached to
      Gore-Tex Periodontal Material. Two case reports are presented to demonstrate the
      successful use of the soft tissue patch augmented with hydroxylapatite in
      patients exhibiting furcation involvement and severe vertical osseous defects.

PMID- 1392504
TI  - The influence of Ulrich von Hutten's medical descriptions and metaphorical use of
      medicine.

PMID- 1392505
TI  - Ottoman medicine and transculturalism from the sixteenth through the eighteenth
      century.

PMID- 1392506
TI  - Quackery and cookery: Justus von Liebig's extract of meat and the theory of
      nutrition in the Victorian age.

PMID- 1392507
TI  - Cortisone, 1949: a year in the political life of a drug.

PMID- 1392508
TI  - H. H. Dale's account of the standardization of insulin.

PMID- 1392509
TI  - In memoriam: John B. de C. M. Saunders (1903-1991).

PMID- 1392510
TI  - The fate of collagen during experimental liver lesion with carbon tetrachloride
      in the presence and absence of colchicine.
AB  - Collagen was examined during experimental lesion of the liver with carbon
      tetrachloride in the presence and absence of colchicine. The experimental animals
      were Wistar rats, young, of both sexes. The fate of collagen was determined by
      quantitative assessment of the soluble fraction in salts (NSC), of the soluble
      fraction in acids (ASC) and of the insoluble fraction (ISC). The results that
      were obtained indicate protective action of colchicine during the experimental
      lesion of the liver with CCl4.

PMID- 1392511
TI  - Introduction of a neuronal network as a tool for diagnostic analysis and
      classification based on experimental pathologic data.
AB  - A neuronal network, as well as uni- and multivariate statistics and a
      discriminant analysis were applied to a morphometric database of 58 cases with
      thyroid neoplasms and normal thyroid tissue. The ability to classify cases
      correctly according to their diagnosis was compared between the neuronal network
      and discriminant analysis. For all pairwise comparisons, classification by
      neuronal network was as least as good as classification by discriminant analysis.
      For some comparisons, the neuronal network provided more correct diagnoses than
      discriminant analysis. On the contrary, in a comparison between tumors which are
      not significantly different according to multivariate statistics, the network
      reclassifies only half of the cases correctly, whereas discriminant analysis
      falsely suggests the possibility of classifying cases with either diagnosis. Our
      results confirm a higher sensitivity of the neuronal network to the diagnostic
      information contained in the present morphometric database, and we will therefore
      use this concept for analysis and diagnostic classification in further
      morphometric studies.

PMID- 1392512
TI  - Metastasis induction by incomplete tumor resection. A new metastasis model using
      inoculation sarcomas in adult nude mice after long-term cultivation of sarcoma
      cells.
AB  - In searching an animal model to study metastasis formation we used cultured cells
      of experimental rhabdomyosarcomas and their inoculation tumors in adult nude
      mice. Supplementing earlier observations (Katenkamp et al. 1987) we found that
      long-term cultured sarcoma cells induce tumors in adult nude mice which do not
      metastasize spontaneously but produce lung metastases after repeated incomplete
      tumor removal. Possible factors and mechanisms responsible for metastasis
      emergence are discussed. The metastasis model introduced may be apt to study
      cellular changes at cytogenetic and molecular biological level that occur during
      tumor progression and metastatic dissemination.

PMID- 1392513
TI  - Lymphatic absorption of 3-phenylamino-1,2-propanediol and its esters.
AB  - From oils associated with the toxic syndrome have been isolated 3-phenylamino-1,2
      aminophenol (PAP) and diesters with fatty acids in addition to fatty anilides.
      These substances have been obtained by chemical synthesis and administered orally
      to rats whose lymphatic canal had previously been cannulated. The lipid fraction
      of the lymph collected at different time intervals was isolated. Its
      chromatographic study has confirmed the presence of the mentioned substances, as
      well as a metabolite of them, demonstrating that these products enter the blood
      by lymphatic absorption.

PMID- 1392514
TI  - Ultrastructure and cell surface studies of cancer cells following vitamin C
      administration.
AB  - Basal cell carcinomas in rats and squamous cell carcinomas in mice induced by a
      topical administration of a chemical carcinogen 3-methylcholanthrene (MCA) a
      single dose of 800 micrograms, were significantly reduced in number and size
      following a combined administration of vitamin C, a daily dose of 50 mg/kg b.wt.
      and MCA for 9 months. Ultrastructural studies of basal cancer cells and squamous
      cancer cells revealed an advanced cytolysis and disorganization of neoplastic
      cells, mitochondrial alterations, nuclear and nucleolar reduction, and increased
      phagolysosomes formation, following vitamin C and MCA administration compared to
      that of neoplastic cells following MCA alone. Scanning electron microscopic
      observations also revealed cytolysis, increased collagen synthesis, and cell
      disorganization with membrane disruption following vitamin C and MCA
      administration, as compared to round basal neoplastic or polyhedral squamous
      neoplastic cells following MCA treatment alone. These findings demonstrate that
      vitamin C exerts its antineoplastic effects by increasing cytolytic and
      autophagic activity, cell membrane disruption, and increased collagen synthesis,
      and thus, inhibits cancer cell metabolism and proliferation.

PMID- 1392515
TI  - Effect of myotonia induced by anthracene-9-carboxylic acid on mitochondrial
      calcium, plasma creatinine-phosphokinase and aldolase activity in the rat.
AB  - The frequent association of myotonia with dystrophy and the knowledge that
      calcium is increased in injured skeletal muscle cells suggest a possible
      relationship between cell calcium and myotonic alterations. This investigation
      has been performed to study the role of calcium in experimental myotonia induced
      by anthracene-9-carboxylic acid (9-AC) in rats treated with several regimens of
      food and exercise. Thirty-two rats were divided into 4 groups of 8 rats each, one
      control and 3 experimental groups. The treatments included caffeine plus exercise
      (group 2), and a calcium-rich diet (group 3); these procedures were designed to
      increase intracellular calcium; another group was treated with 9-AC as a myotonia
      inducer (group 4). The treatment for all groups lasted 60 days. No significant
      differences in plasma sodium, potassium, chloride and calcium between control and
      experimental groups were observed. Whole muscle calcium in wet tissue samples did
      no change with any treatment. On the contrary, mitochondrial calcium showed a
      significantly higher concentration in group 3 and 4. CPK and aldolase activities
      in groups 1, 2 and 3 were similar; but in group 4 these enzyme activities were
      significantly higher (p less than 0.05). The electrical and mechanical responses
      were not altered in any rat with any experimental treatment. Our data suggest
      that myotonia is a predisposing factor for an altered mitochondrial calcium
      homeostasis in this model; in addition, the enzyme activities of CPK and aldolase
      were increased in the rats of group 4 implicating that myotonia is a crucial
      factor in the development of enzymatic abnormalities.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1392516
TI  - Gross and histologic effects of topical misoprostol on canine gastric mucosa.
AB  - This study reports the histological effects of topical misoprostol, a synthetic
      PGE1 analog, administered in varying dosages on the resting canine gastric
      mucosa. Misoprostol did not macroscopically or microscopically damage the mucosa
      but its presumed permeability effects on the gastric vasculature induced marked
      edema of the mucosa and submucosa. Consistent features included increased
      thickness of both layers, dilated interglandular regions of the lamina propria,
      marked subepithelial edema, reduced depth and width of gastric foveolae,
      vasodilation of the vascular channels, reduced height of surface epithelial
      cells, swelling of their basolateral intercellular spaces, and increased amounts
      of surface adherent mucus. It is speculated that the mucosal edema, in addition
      to an increased mucus layer, may be important in the mechanism of gastric
      cytoprotection by increasing the distance of penetration or absorption for a
      mucosal-damaging agent, diluting its concentration, and disseminating any focal
      accumulations of red blood cells.

PMID- 1392517
TI  - Ultrastructural analysis of pulmonary alveolar proteinosis induced by
      methylnaphthalene in mice.
AB  - Pulmonary alveolar proteinosis was induced at a 100% incidence in B6C3F1 female
      mice by twice weekly painting the back skin with methylnaphthalene for 30 weeks
      to give a total dose of 7.14 g/kg b.wt. Semithin sections were used for defining
      areas of type II pneumocyte hyperplasia and hypertrophy and associated
      proteinosis. Ultrastructurally, alveolar spaces were found to be filled with
      numerous myelinoid structures resembling the lamellar bodies of type II
      pneumocytes. Mononucleated giant cells (balloon cells, BC) containing numerous
      myelinoid structures, lipid droplets and many electron dense amorphous ascicular
      crystals were closely associated with this extracellular membranous material.
      Stacks of elastic fibers stained with tannic acid and bundles of collagen fibers
      were loose and discontinuous in the interstitium of affected areas. The following
      pathogenesis is hypothesized: type II pneumocytes produce increased amounts of
      lamellar bodies due to their hyperplasia and hypertrophy and develop to form BC
      which liberate numerous myelinoid structures on their rupture. Epidermal
      absorption of methylnaphthalene is an efficient reliable method of induction of
      this internal disease.

PMID- 1392519
TI  - Lipid peroxidation--a common pathogenetic mechanism?
AB  - Lipid peroxidation is considered at present as one of the basic mechanisms
      involved in reversible and irreversible cell and tissue damage. The current
      knowledge about the role of peroxidative breakdown of polyunsaturated fatty acids
      in the pathogenesis of various diseases has been reviewed. Lipid peroxidation
      leads to degradation of the lipid membrane, interaction of degradation products
      with intra- and extracellular targets and to the production of new reactive
      oxygen species during the course of the chain reaction thus leading to damage of
      cells and tissues. According to our current view lipid peroxidation is implicated
      in the pathogenesis of cancer, inflammatory processes, atherosclerosis, toxic
      injury by xenobiotics and ischemic-reperfusion damage.

PMID- 1392518
TI  - Atypical malignant mesotheliomas with osseous and cartilaginous differentiation
      after intraperitoneal injection of various types of mineral fibres in rats.
AB  - The histopathological appearance of malignant mesotheliomas with osseous and
      cartilaginous differentiation is described in detail. Bone and cartilage occurred
      in mixed and sarcomatoid mesotheliomas which were induced by intraperitoneal
      injection of various types of asbestos fibres (asbestos cement, crocidolite, UICC
      amosite, UICC-chrysotile B, Calidria-chrysotile). Bone or cartilage were found in
      32.7% of mixed mesothelioma and in 12.8% of sarcomatoid mesotheliomas.

PMID- 1392520
TI  - Cardiac metastases of induced lung carcinomas in rats.
AB  - A detailed study was made of seven cardiac metastases resulting from induced lung
      carcinomas. Fifty-six metastasizing lung carcinomas were found in Hann: Wistar
      rats as a result of subcutaneous injection of DPNA (dipentylnitrosamine). Of
      these 56, seven (12.5%) metastasized to the heart (three adenocarcinomas and four
      adenosquamous carcinomas). The metastatic tumors were located in the epicardium,
      myocardium, or endocardium, and their histologic appearance conformed to that of
      the primary lung carcinomas. The frequency of the cardiac metastasis and the
      preference of location within the heart were comparable with human cases.

PMID- 1392521
TI  - Effects of N'methyl-N'-nitro-N-nitrosoguanidine and deoxycholic acid on the
      content of free radicals in rat serum.
AB  - The aim of this study was to determine whether changes in serum free radicals may
      be useful for the early detection of precancerous conditions in the rat colon
      after treatment with a direct carcinogen (N-Methyl-N'-Nitro-N-Nitrosoguanidine,
      MNNG) and a secondary bile acid (deoxycholic acid, DCA) as a tumor promoter. It
      was shown that a significant increase in the concentrations of free radicals in
      sera of rats following their treatment with MNNG and DCA was observed as early as
      the 18th week after the beginning of the treatment. Since our results have shown
      that these alterations occurred in parallel with neoplastic transformations in
      the rat colon, it suggests that the increase in serum free radicals reflected the
      precancerous situation in the animals and may be useful in the early detection of
      cancer development. The possible role of free radicals in deoxycholate-induced
      liver toxicity was discussed.

PMID- 1392522
TI  - Ultrastructural investigations of the enterochromaffin-like (ECL) cells in three
      different rat strains (Sprague-Dawley, Fischer 344, Wistar) after treatment with
      the H+,K(+)-ATPase inhibitor pantoprazole.
AB  - The purpose of the present study was the evaluation of ultrastructural
      characteristics of the enterochromaffin-like (ECL) cells in the fundic mucosa of
      three different rat strains without treatment and after treatment with the H+,
      K(+)-ATPase inhibitor pantoprazole. In the study, 20 one year old female Sprague
      Dawley (SD), Fischer 344 (F) and Wistar (W) rats each were treated orally for
      three months with 4 mg pantoprazole/kg/d or with the vehicle only. The control
      animals showed close conformity of ECL cell density and morphology in all three
      strains. Treatment with pantoprazole led to a significant increase in serum
      gastrin concentration and GPC density in all strains. However, the electron
      microscopically determined ECL cell density was markedly increased in the SD
      strain only. Ultrastructurally all treated rats showed activation of the ECL
      cells, and enhanced histamine release. The SD and F strains had an enhanced
      proportion of large ECL cell granules, with the F rats also showing an increased
      granule density. In contrast, the treated W rats were found to have a lower
      granule density and a higher proportion of small and medium sized granules
      compared to their controls.

PMID- 1392523
TI  - Role of lipid peroxidation in enhancement of endotoxin hepatotoxicity.
AB  - The present study was undertaken in the rats to examine whether endotoxin
      hepatotoxicity is enhanced by increased lipid peroxidation. The rats were given
      10 ml of water, corn oil or heated and oxygenated corn oil per kg body weight by
      stomach tube twice a day for 14 days, and then they were injected physiological
      saline solution or endotoxin (2 or 2.5 mg per kg body weight) into the tail vein.
      In the rats pretreated with water or corn oil, the activity of serum glutamic
      pyruvic transaminase was within the normal limit, and there was no conspicuous
      morphological change in the liver, except for accumulation of fine fat droplets
      in few liver cells. On the other hand, in the rats pretreated with heated and
      oxygenated corn oil, containing a large amount of lipid peroxides, accumulation
      of small fat droplets in the liver cells and a slight elevation of serum
      transaminase activity were induced. The challenge with endotoxin (2.5 mg per kg
      body weight) caused focal hepatocellular coagulative necrosis and a marked
      elevation of serum transaminase activity, irrespective of the sorts of
      pretreatment, and there was no significant difference in the biochemical change
      and the histopathological damage between the rats pretreated with water, corn oil
      and heated and oxygenated corn oil. These results suggest that increased lipid
      peroxidation does not contribute to the enhancement of endotoxin hepatotoxicity,
      although it is thought that carbon tetrachloride and ethanol enhance endotoxin
      hepatotoxicity by synergism between endotoxin and the chemicals through lipid
      peroxidation.

PMID- 1392525
TI  - Why do women smoke?
AB  - This paper will examine the relationship between the dramatic increase of smoking
      for women while the numbers of male smokers decreases. The powerlessness which
      characterises women's relationships with all other social groups and individuals
      is addressed.

PMID- 1392524
TI  - Mononuclear cells in normal colon and colonic carcinoma express the same T cell
      activation markers.
AB  - The proportion of mononuclear cells (MC) expressing some of the T cell activation
      markers in normal colon and colonic carcinomas was determined by immunoperoxidase
      staining and computer-assisted video image analysis (VIA). Tissue sections were
      stained with monoclonal antibodies against the T cell activation markers which
      included the MHC class II antigens DR, DP and DQ, interleukin 2 receptor (CD25)
      and the p180 (CD45RO) form of the leucocyte common antigen. The mean values for
      the proportion of leucocytes expressing these activation markers were 92% for DR,
      61% for DP, 68% for DQ and 60% for CD45RO in tumours and 90, 62, 70 and 55% in
      normal tissue respectively. Few cells were stained for the IL2 receptor (mean
      values 7% for tumours and 5% for normal tissue) or the p220 form (CD45RA) of the
      leucocyte common antigen (mean values 6% for tumours and 4% for normal tissue).
      The proportion of MC bearing any of these markers in the normal colon was not
      significantly different from the matched colonic carcinomas.

PMID- 1392526
TI  - The invisibility of nurses in the workplace.

PMID- 1392527
TI  - Private enterprise occupational health.
AB  - A private company in Palmerston North is providing occupational health services
      to the Manawatu. From an initial concept in mid-1987, the business commenced
      operations in early 1988. The concept has changed, the shareholding has changed
      but the business has survived and, by means of plenty of hard work, grew rapidly
      in 89 and 90, looks likely to achieve a 20% increase in gross turnover in 91/92
      and has budgeted for an 11% increase in turnover for 92/93. A.C.C. legislative
      changes have provided a new opportunity and this is being explored. The new
      Health and Safety legislation should provide increased opportunities but so far
      there is little evidence of this occurring. However hope springs eternal and we
      are confident that we can see through the current hard times and that eventually
      an improved economy and a settled down health system will allow us to provide
      increased services for the benefit of the local community.

PMID- 1392528
TI  - Community assessment.

PMID- 1392529
TI  - Introducing Ruby Taunoa. Interview by Wendy Porter.

PMID- 1392530
TI  - Making a difference.

PMID- 1392531
TI  - Empowerment.

PMID- 1392532
TI  - HIV infection and universal precautions: why are health workers so fearful given
      the facts?
AB  - Identifying people who are infected with HIV has drawn significant media
      attention over the past decade. This is an ethical issue that must be dealt with
      by health care workers, urgently. Services to people with HIV are being
      compromised by the attitudes and practices of some health care workers. Infection
      control nurses should provide leadership to health care workers who share the
      challenge of delivering effective and efficient services to people with HIV/AIDS.

PMID- 1392533
TI  - A critical reconceptualisation of the environment in nursing: developing a new
      model.
AB  - This paper describes the use of feminist theory and critical social theory in the
      development of a new nursing model. Basic concepts of the model are defined, and
      the need for reconceptualisation of the environment is discussed. There is no
      suggestion that this model is in any way complete; rather it represents an
      exploration of some of the possibilities. In the second part of this paper the
      concepts of the model are explored in planning interventions for young women with
      a smoking habit or with disordered eating.

PMID- 1392534
TI  - Systemic human antisense therapy begins.

PMID- 1392535
TI  - The detection of oligodeoxynucleotide molecules following uptake into mammalian
      cells.
AB  - A mixed phosphodiester:phosphorothioate oligodeoxynucleotide was used in uptake
      studies with T15 mouse fibroblast cells. The presence of full-length unlabeled
      oligomers was identified in both cytoplasmic and nuclear extracts by a method
      involving gel electrophoresis and electroblotting followed by hybridization with
      a complementary radiolabeled probe. Detection did not depend on the presence of a
      label on the oligomer with the potential for its removal, often a problem in
      other studies. The fate of the oligonucleotides could then be followed with time
      for at least 3 days. This method of detection should be applicable to studies of
      nuclease resistance and uptake characteristics of newly developed oligonucleotide
      analogues.

PMID- 1392536
TI  - Antisense effect of oligodeoxynucleotides with inverted terminal internucleotidic
      linkages: a minimal modification protecting against nucleolytic degradation.
AB  - The synthesis of a new class of antisense oligonucleotide compounds with 3'-3'
      and 5'-5' end inversion (INV-oligonucleotides) is described. Besides the
      advantage of simplicity of synthesis, physico-chemical studies show that these
      compounds do not disturb Watson-Crick base-pairing. INV-oligonucleotides have a
      half-life of 30 h in human serum. We show that they are capable of inhibiting
      SV40 large T-antigen expression in COS-1 cells, both in vitro and in vivo, and by
      modulation of the expression of cellular oncoprotein p53 in vitro.

PMID- 1392537
TI  - Injection of Antisense RNA specific for E-cadherin demonstrates that E-cadherin
      facilitates compaction, the first differentiative step of the mammalian embryo.
AB  - We have investigated the effect of antisense E-cadherin RNA in the
      preimplantation mouse embryo. Antisense RNA was injected into each cell of two
      cell embryos that were cultured for 2 days until the normal time of compaction
      and scored for abnormalities. Embryos injected with the antisense RNA showed
      delayed compaction compared to the embryos injected with control, or sense, RNA.
      Delayed cleavage was not the cause because nuclear staining with Hoechst dye
      33258 showed about the same number of nuclei in both uncompacted embryos injected
      with antisense RNA compared with compacted embryos injected with sense RNA at the
      same hours post human chorionic gonadotropin (hCG). Immunofluorescence with a
      monoclonal antibody to E-cadherin was markedly diminished in embryos injected
      with antisense RNA compared with control, injected embryos, suggesting that the
      observed delayed compaction is due to the inhibition of E-cadherin gene
      expression by antisense RNA. Embryos injected with antisense RNA eventually
      compacted and then expressed E-cadherin, but at lower apparent levels than
      controls. Injection of a single blastomere at the two-cell stage created half
      embryo abnormalities.

PMID- 1392538
TI  - Liposomes as a drug delivery system for antisense oligonucleotides.
AB  - Antisense oligonucleotides seem to provide a promising new tool for the therapy
      of viral diseases and of cancer. However, before the therapeutic potential of
      antisense compounds can be fulfilled, it will be necessary to overcome
      significant problems relating to their inefficient uptake by cells and their
      rapid loss from the body. Phospholipid vesicles (liposomes) have been widely used
      as a drug delivery system for standard anticancer and anti-infectious drugs. In
      this article we examine the potential role of liposomes as a drug delivery system
      for antisense oligonucleotides.

PMID- 1392540
TI  - Prognostic implication of gastroparesis in patients with diabetes mellitus.
AB  - The prognosis and survival in 13 patients with Type II diabetes mellitus who had
      delayed gastric emptying as shown by radionuclide tests performed between August
      1985 and August 1987 was determined in July 1990. The two patients that were over
      80 years of age died within 18 months of the diagnosis of diabetic gastroparesis,
      but ten of the remaining eleven patients survived. The clinical data on these
      patients suggest that despite the usual presence of significant co-existent
      pathology, gastroparesis diabeticorum carries a less ominous prognosis than
      currently believed.

PMID- 1392539
TI  - Cardiovascular reflexes in Parkinson's disease: effect of domperidone and
      apomorphine.
AB  - Cardiovascular reflexes were evaluated in 18 patients with idiopathic Parkinson's
      disease who had a Hoehn & Yahr score of III-IV. The effect of apomorphine and
      domperidone on blood pressure, heart rate, R-R interval variation, and the
      Valsalva ratio were studied. Autonomic dysfunction was not found in the patients
      and there were no differences between subgroups of patients on different
      treatments. Apomorphine altered cardiovascular reflexes to a greater degree in
      patients who received the drug for the first time than in chronically treated
      patients. The changes were antagonized by domperidone, a peripheral dopamine
      receptor antagonist. Apomorphine treated patients who were receiving long-term
      domperidone had similar abnormalities of cardiovascular reflexes to those who had
      been able to withdraw it.

PMID- 1392541
TI  - Cardiovascular responses elicited by simulated diving and their habituation in
      man.
AB  - The cardiovascular responses of 24 subjects were investigated under various
      simulated diving conditions. Muscle blood flow in forearm and calf, arterial
      pressure, heart rate and intrathoracic pressure were monitored. Breath holding
      with face immersion in water at 18 degrees C gave a typical diving response at
      intrathoracic pressure of 0 and 20 mmHg, (23% bradycardia, greater than 60%
      muscle vasoconstriction). Breath holding alone at 20 mmHg intrathoracic pressure
      resulted in vasoconstriction (50%) and bradycardia (4%). Breath holding at 0 mmHg
      intrathoracic pressure induced a muscle vasoconstriction (5%). These results
      indicate that both increased intrathoracic pressure and facial immersion can
      produce a typical diving response individually but that the full 'diving
      response' requires the presence of both conditions. Diving often activated two
      responses, the typical 'diving response' and a superimposed defence reaction.
      Cardiovascular components of the defence reaction (muscle vasodilatation and
      tachycardia) which was elicited in some divers masked the diving response. In
      those subjects in whom the diving response was initially absent during repetition
      of diving manoeuvres the cardiovascular components of the defence reaction were
      habituated and the characteristic diving response gradually emerged: the initial
      tachycardia diminished and was replaced by bradycardia, while vasodilatation in
      the forearm and calf was replaced by vasoconstriction.

PMID- 1392542
TI  - Differential effects of isometric exercise on the cutaneous circulation of
      different regions.
AB  - Studies have been made in healthy human subjects of the changes evoked by
      isometric hand grip in arterial pressure, heart rate and cutaneous red cell flux,
      the latter being recorded using a laser Doppler meter. Hand grip for 2 min evoked
      increases in arterial pressure and heart rate, the magnitude of which were graded
      with the force of contraction (75, 50, or 25% maximum voluntary contraction).
      Cutaneous red cell flux in the contralateral forearm decreased significantly
      during 25 and 50% maximum voluntary contraction, while the cutaneous vascular
      resistance (arterial pressure/cutaneous red cell flux) increased to extents that
      were graded with the maximum voluntary contraction, indicating graded
      vasoconstriction. By contrast, cutaneous red cell flux in the face tended to
      increase, this reaching significance at 75% maximum voluntary contraction.
      Cutaneous vascular resistance in the face increased in some subjects, but
      decreased in others, vasodilator responses being most common during 75% maximum
      voluntary contraction when sweating commonly appeared on the face. In the dorsum
      of the foot, red cell flux did not change during 75% maximum voluntary
      contraction, although foot cutaneous vascular resistance increased significantly
      by the end of the first minute of contraction. At 50 and 25% maximum voluntary
      contraction most subjects showed an increase in foot cutaneous vascular
      resistance, but the remainder showed a decrease. We propose that isometric hand
      grip causes vasoconstriction in the cutaneous circulation of the contralateral
      forearm, the face and foot, that this response is strongest in the forearm and
      weakest in the face, and that in the face and foot, the vasoconstriction may be
      overcome by vasodilatation secondary to sweating.

PMID- 1392544
TI  - The long-term reproducibility of clinical tests of autonomic cardiovascular
      function in normal man.
AB  - Tests for the integrity of autonomic cardiovascular reflexes have been widely
      used in the clinic and in space physiology for decades. However, whereas some
      information on the short-term reproducibility of such tests are available, little
      is known about their long-term reproducibility. The work in this study was,
      therefore, directed towards assessing intra- and inter-subject variations in
      responses (heart rate, mean arterial blood pressure, forearm blood flow and
      forearm vascular conductance) to cortical arousal, cold face stimulation and
      lower body negative pressure (at 10, 30 and 50 mmHg) in eleven healthy male
      subjects (aged between 22 and 45 years). Subjects were studied repeatedly (each
      month) over a 6-month period. It was found that forearm vascular conductance
      responses to cold face stimulation were the most reproducible (mean coefficient
      of variation 10.9%), and with diminishing reproducibility curve responses to
      lower body negative pressure at 50 mmHg (mean coefficient of variation 12.4%),
      lower body negative pressure at 30 mmHg (mean coefficient of variation 18.9%),
      lower body negative pressure at 10 mmHg (mean coefficient of variation 28.0%),
      and responses to cortical arousal (mean coefficient of variation 39.6%).
      Generally, subjects who showed the largest responses to cold face stimulation
      also showed the largest responses to the other tests, and vice versa. It is
      concluded that there is intra-individual variability in the responsiveness and
      reproducibility of cardiovascular tests and that the cardiovascular responses to
      cold face stimulation and lower body negative pressure at 50 mmHg are the most
      reproducible.

PMID- 1392543
TI  - Reduced vascular excitatory responses to cardiopulmonary unloading in
      hypertensive patients with left ventricular diastolic dysfunction.
AB  - Physiological consequences of altered peak left ventricular diastolic filling
      rate in hypertension have not yet been fully assessed. The hypothesis that
      altered left ventricular diastolic filling rate interferes with inhibitory
      cardiopulmonary reflexes was tested. Normalized peak left ventricular diastolic
      filling rate was calculated from radionuclide ventriculography. Haemodynamic
      changes during lower body negative pressure (-5 to -40 mmHg) in nine hypertensive
      patients with slow normalized left ventricular filling rate (Group A) were
      compared with 16 hypertensive patients with normal normalized peak left
      ventricular diastolic filling rate and ten normal volunteers of the same age
      group. Baseline total peripheral resistance was higher in essential hypertension
      compared to normals but did not differ significantly between the two hypertensive
      groups. For data analysis, the levels of lower body negative pressure were
      grouped as low levels of -5 to -10, and -15 to -20 mmHg, an intermediate level of
      -25 mmHg, and high levels of -30 to -40 mmHg; the change in total peripheral
      resistance (from baseline) was less prominent in Group A compared to Group B and
      to normals (-1.4 +/- 1.7 [SE], -0.06 +/- 1.4, 1.1 +/- 1.2 and 4.5 +/- 2 u.M2 in
      Group A at the four consecutive levels of lower body negative pressure vs. 0.9 +/
      0.7, 3.8 +/- 0.9, 7.2 +/- 1.6, and 8.2 +/- 1.4 in Group B, and 2.0 +/- 0.7, 3.3
      +/- 0.8, 4.9 +/- 0.8, and 5.6 +/- 1.0 in normals). The reductions in central
      venous pressure and in pulmonary wedge pressure were not significantly different
      among the three groups at the different levels of lower body negative pressure,
      but the reduction in cardiac output was smaller in patients with reduced dv/dt
      ratio than in the other two groups. The responses to the cold pressor test were
      similar in all subjects. We conclude that patients with essential hypertension
      and diastolic dysfunction have impaired total peripheral resistance responses to
      lower body negative pressure. This abnormality may reflect an alteration in
      cardiac baroreflexes secondary to left ventricular diastolic dysfunction, an
      influence of baseline sympathetic activity on the observed vascular
      responsiveness to lower body negative pressure, or primary differences among
      groups in the changes in cardiac output induced by similar levels of lower body
      negative pressure.

PMID- 1392545
TI  - The effect of time of day on orthostatic tolerance and the cardiovascular effects
      of a high carbohydrate meal in healthy young subjects.
AB  - Ingestion of a high carbohydrate meal leads to a fall in blood pressure but does
      not change orthostatic tolerance in healthy elderly subjects. Much smaller
      effects are observed in young subjects, but studies have only been performed in
      the morning. The purpose of this study was to compare orthostatic responses and
      the effect of a high carbohydrate meal in the morning and in the afternoon in
      young subjects. Fourteen healthy, young subjects (four female, mean BMI = 22.0
      kg/m2, age range 21-27 years) were studied on two occasions, in the morning (0830
      h) and in the afternoon (16.30 h) on separate days. Blood pressure, heart rate
      and cardiac output were measured noninvasively before and after the ingestion of
      a standard meal with 76-77% of the energy being provided by carbohydrate. Time of
      day had no effect on blood pressure and heart rate responses to tilting after
      food. Cardiac output fell significantly during tilting in the fasted state. In
      the morning there was a progressive fall in cardiac output with a decrease of
      0.83 l/min at 45 degrees (95% confidence interval of the change -1.37 to -0.27 to
      l/min) and a fall of a further 0.15 l/min at 75 degrees. By contrast in the
      afternoon cardiac output fell 0.84 l/min at 45 degrees (95% confidence interval
      of the change -1.31 to -0.35 l/min) and then rose by 0.61 l/min on tilting to 75
      degrees (95% confidence interval of the change +0.22 to +0.98 l/min. Interaction
      effect p = 0.02 ANOVA). Supine cardiac output increased after food ingestion at
      both times of day (p less than 0.01 ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392546
TI  - Parasympathetic denervation of the iris in Chagas' disease.
AB  - The parasympathetic innervation of the iris along with cardiovascular reflexes
      involving parasympathetic and sympathetic function were studied in 45 patients
      with Chagas's disease and in 36 controls. The autonomic features in Chagas'
      disease included 15 with cardiomyopathy, three with megaoesophagus and five with
      megacolon. None of the patients had orthostatic hypotension. Parasympathetic
      cardiac reflexes (deep breathing 30:15 ratio, Valsalva) were abnormal. There were
      exaggerated pupillary responses to dilute pilocarpine. These studies suggest iris
      parasympathetic denervation and favour more widespread cholinergic involvement in
      patients with Chagas' disease, than previously recognized.

PMID- 1392547
TI  - Severe paroxysmal hypertension induced by a subconscious Valsalva-like
      manoeuvres.
AB  - We describe the case history of a 32 year old male with severe paroxysmal
      hypertensive spikes when there was an increase in diastolic blood pressure to 150
      200 mmHg. These spikes occurred during rest and especially during modest
      exercise. They were associated with headache and dyspnoea and were resistant to
      antihypertensive medication. After 5 years of observations and investigations he
      underwent further 24-h intra-arterial blood pressure monitoring and physiological
      testing. The 24-h blood pressure profile was near normal at rest. The observed
      hypertensive spikes seemed to be induced by involuntary Valsalva-like manoeuvres.
      This had not been detected previously by the investigators and the patient was
      unaware of inducing these manoeuvres.

PMID- 1392548
TI  - Opening up addictions training.

PMID- 1392549
TI  - Alcohol and drug abuse in Nepal.
AB  - Alcohol use has been in Nepal since time immemorial. Social tolerance to alcohol
      use is quite high and so far alcohol has not been taken seriously either by the
      Government or by any social organization. Production, sale, and consumption of
      alcohol is ever on the increase and it could be taken as the number one problem
      drug in the country. Cannabis and opium use has been in Nepal for centuries and
      in the past they did not pose much of a problem. Drug use began to be seen as a
      problem since only the mid-1960s and early-1970s with the influx of large numbers
      of hippies. Presently, the drug scene in Nepal is dominated by heroin and it has
      affected youths, mainly in the urban areas. A number of measures, both on supply
      reduction and demand reduction, have been taken by the Government together with
      non-Governmental organizations. However, the number of drug users is on the
      increase. Relapse rate following detoxification treatment is quite high. After
      care and rehabilitative measures are lacking. Many drug users become involved in
      high-risk behaviours in spite of their knowledge of the dangers. Therefore, it
      calls for the change in our strategies which must be based on the thorough
      understanding of human nature and its behaviour.

PMID- 1392550
TI  - Implications of gender for alcohol treatment research: a quantitative and
      qualitative review.
AB  - Previous reviews of alcohol treatment research have indicated that in the
      majority of studies there are no sex differences in treatment outcome. The
      current meta-analysis was used to measure the magnitude and direction of trends
      of sex difference in treatment outcome. The results indicated that women had
      better treatment outcomes than men in the first 12 months after treatment while
      men showed greater improvement than women in follow-ups after 12 months. However,
      the estimated differences were small and derived from a heterogeneous sample of
      studies. Evidence from the studies in the meta-analysis is used to highlight the
      importance of gender-related factors which may impact on the processes and
      outcomes of treatment. In particular, sex differences in physiological responses
      to alcohol, in social norms for alcohol, and in socio-cultural experiences are
      considered important areas for future investigation in alcohol treatment
      research.

PMID- 1392551
TI  - User reports of problems associated with alcohol and marijuana.
AB  - A general population sample of 5126 New Zealanders aged 15-45 in two regions was
      surveyed to determine their use of alcohol, tobacco, marijuana, and other illicit
      drugs. Self-reported problems were recorded on identical scales for alcohol and
      marijuana in order to make a direct comparison between alcohol and marijuana
      related problems. The results suggest that alcohol-related problems were more
      common than marijuana-related ones in the general population, reflecting the fact
      that alcohol use was more widespread. Within the 17% of the sample who had used
      both alcohol and marijuana in the last 12 months more problems were reported from
      alcohol, once again reflecting differences in amounts consumed. Among heavier
      users of marijuana both alcohol and marijuana-related problems were more commonly
      reported than in the general sample. Problems were reported at similar levels for
      both drugs and the pattern of problems is somewhat similar.

PMID- 1392552
TI  - Predicting initiation to and cessation of buprenorphine and temazepam use amongst
      adolescents.
AB  - Two interviews separated by 12 months (mean) were conducted with a purposive
      sample of Glaswegian adolescent drug misusers. Across that interval, beginning to
      use buprenorphine and temazepam were predictable by prior extent of other
      substance use, especially cannabis and tobacco, and by the Drug Misuse Scale,
      using selected MMPI items. About 50% of those who had been using either drug
      prior to first interview did not use at all between first and second interview.
      For temazepam, this cessation was not predictable, but ceasing to use
      buprenorphine was more likely the less time subjects had used this drug and if
      they had never injected. It is concluded that personality and frequent substance
      use predispose to drug misuse, but that additional factors must lead to
      dependence.

PMID- 1392553
TI  - Cigarette smoking and cognitive performance.
AB  - While some investigations into the relationship between smoking and cognitive
      performance have reported that smoking facilitates performance, other research
      has come to the opposite conclusion. A review of the literature suggests that
      this variance in results may be due to differences among studies in design
      (comparing smokers only with deprived smokers rather than with non-smokers) and
      also to differences in task demands. Therefore, performance of smokers having
      just smoked, matched smokers deprived for a brief period, and also non-smokers
      was contrasted on a series of tasks which ranged from repetitive and perceptually
      bound tasks to complex, dynamic tasks dependent upon long-term memory. It was
      found that while cigarette smoking had no negative effect upon performance for
      simple perceptual tasks, smoking was found to exert measurable negative effects
      upon performance for more complex information processing tasks.

PMID- 1392554
TI  - The anatomy of a follow-up.
AB  - This article describes the methods that were used to maximize subject retention
      in an 8-12 year follow-up study of 454 men. Guidelines and suggestions are given
      regarding follow-up structure, strategies to relocate lost subjects, and efforts
      to maintain contact and ensure subject cooperation. Through these methods all 454
      subjects have been located, and at the present time an estimated 98% or greater
      will be completely evaluated at follow-up. Hopefully these suggestions will be
      helpful to researchers and clinicians interested in longitudinal studies.

PMID- 1392555
TI  - Predictors of smoking behaviour: an application of Ajzen's theory of planned
      behaviour.
AB  - The aim of the present paper was to verify the basic assumptions underlying the
      theory of planned behaviour for the prediction of cigarette smoking intentions
      and behaviour among adults of the general population (study 1) and a group of
      pregnant women (study 2). Each study was developed based upon Ajzen's theory of
      planned behaviour. In both studies, baseline data was collected at home with
      trained interviewers and with the use of paper and pencil questionnaires. The
      self-report on behaviour was obtained 6 months (study 1) and between 8 and 9
      months (study 2) after baseline data collection. In study 1, for smokers,
      perceived behavioural control, attitudes and subjective norm were explaining
      intention, whereas perceived behavioural control and habit were the most
      important predictors of behaviour. In study 2, smoker's intentions was mainly
      under the influence of perceived behavioural control and attitude, whereas
      behaviour was predicted by perceived behavioural control only. The present
      studies suggest that promotional programmes should help smokers to know and
      develop their will-power regarding non-smoking of cigarettes and should be
      informed of the effort required in order to modify smoking behaviour.

PMID- 1392556
TI  - The incidence of illicit drug use in the United States, 1962-1989.
AB  - Epidemiological descriptions of drug abuse in the US in the last three decades
      have generally not included data on the patterns and trends in the incidence of
      illicit drug use (i.e. new users). In this paper, estimates of illicit drug use
      incidence are presented, based on retrospective data from the National Household
      Survey on Drug Abuse. Incidence of marijuana use began increasing in the 1960s
      and reached a peak in 1973, after which a continuing decline was seen. Cocaine
      use incidence began to increase in the late 1960s and reached a peak in 1982,
      then declined.

PMID- 1392557
TI  - Health of the nation.

PMID- 1392558
TI  - Drug hangings.

PMID- 1392559
TI  - India's national AIDS plan.

PMID- 1392560
TI  - The role of mass spectrometry in glycobiology.

PMID- 1392561
TI  - Enzyme-linked immunosorbent assays for the measurement of blood group A and B
      glycosyltransferase activities.
AB  - ELISA assays have been developed for alpha(1-3)N-acetylgalactosaminyltransferase
      (blood group A transferase) and alpha(1-3)galactosyltransferase (blood group B
      transferase) activities. In these assays, microtitre plates coated with the
      bovine serum albumin conjugate of a synthetic Fuc alpha 1-2Gal beta-R acceptor
      substrate are incubated with the appropriate nucleotide donor (UDP-GalNAc or UDP
      Gal) and human serum as the enzyme source. The resulting trisaccharide products
      Fuc alpha 1-2(GalNAc alpha 1-3)Gal beta-R-BSA or Fuc alpha 1-2(Gal alpha 1-3)Gal
      beta-R-BSA are detected and quantified with monoclonal antibodies selected not to
      cross-react with the substrate structure. With less than a microliter of human
      serum, product formation is proportional to enzyme concentration and to time of
      incubation of up to 90 min.

PMID- 1392562
TI  - Detection of the ganglioside N-glycolyl-neuraminyl-lactosyl-ceramide by
      biotinylated Escherichia coli K99 lectin.
AB  - K99 lectin from Escherichia coli was purified and biotinylated via its carboxyl
      groups using biocytin hydrazide and a water soluble carbodiimide. Biotinylation
      of two out of the nine carboxyl groups was sufficient to permit detection of the
      lectin by avidin and did not cause any loss of the haemagglutinating activity. It
      was demonstrated that the biotinylated K99 lectin retained other important
      properties of native K99 and that it will probably become a very sensitive
      detecting reagent. Indeed, it was able to bind to HeLa cells, as do intact
      bacteria carrying K99 fimbriae, and also to recognize N-glycolyl-neuraminyl
      lactosyl-ceramide in an overlay binding assay.

PMID- 1392563
TI  - Production and characterization of a monoclonal antibody (BBH5) directed to
      ganglioside lactone.
AB  - The occurrence of lactones in various ganglioside preparations has been clearly
      demonstrated, yet the natural occurrence of ganglioside lactones in cells and
      tissues has been the subject of long debate, since lactones can be formed readily
      during preparation of gangliosides. We now report the generation of monoclonal
      antibody (BBH5) that reacts specifically with lactones of disialogangliosides
      having the NeuAc2-8NeuAc2-3Gal sequence, but does not crossreact with the parent
      ganglioside. The specificity of the antibody resides on the first lactone ring
      between two sialic acid residues but not on the second lactone ring between
      sialic acid and galactose, as evidenced by reactivity with lactonized GD1b having
      the first lactone ring (L1), and by reactivity with lactonized polysialic acid
      homo-oligomers ([NeuAc alpha 2-8]nNeuAc). The sialic acid carboxyl involved in
      the lactone ring was unequivocally determined after ammonolysis followed by
      methylation and fast atom bombardment mass spectrometry. The antibody BBH5 thus
      provides a novel tool for studies of the natural occurrence of lactones in cells
      and tissues.

PMID- 1392564
TI  - Expression, glycosylation and secretion of yeast acid phosphatase in hamster BHK
      cells.
AB  - The gene PHO5 coding for one of the repressible acid phosphatases of the yeast
      Saccharomyces cerevisiae has been expressed at high efficiency in the baby
      hamster kidney (BHK) cell line. The expression vector was constructed from PHO5
      driven by the human beta-actin promoter and was transfected into BHK cells by the
      calcium phosphate method. The recombinant APase (r-APase) which was secreted in
      active form from the cells was estimated by SDS/polyacrylamide gel
      electrophoresis to have molecular mass M(r) = 62,000, indicating substitution of
      the polypeptide moiety by 2-3 asparagine-linked glycans. Analysis by sequential
      lectin affinity chromatography of glycopeptides obtained from r-APase with
      Pronase showed that the glycans are predominantly of the 2.2.4 triantennary and
      tetraantennary complex-type. These data suggest that the extensive glycosylation
      of yeast APase, which contains eight polymannose substituents, is not essential
      for secretion and expression of enzymatic activity of the transfected gene
      product.

PMID- 1392565
TI  - Sequence analysis of p-hydroxyphenyl-O-beta-D-xyloside initiated and radio
      iodinated dermatan sulfate from skin fibroblasts.
AB  - To generate xyloside-primed dermatan sulfate suitable for sequence analysis, skin
      fibroblasts were incubated with p-hydroxyphenyl-beta-D-xylopyranoside and
      [3H]galactose, and free [3H]glycosaminoglycan chains were isolated from the
      culture medium by ion exchange and gel chromatography. After 125I labelling of
      their reducing-terminal hydroxyphenyl groups, chains were subjected to various
      chemical and enzymatic degradations, both partial and complete, followed by
      gradient polyacrylamide gel electrophoresis and autoradiographic identification
      of fragments extending from the labelled reducing-end to the point of cleavage.
      Results of periodate oxidation-alkaline scission indicated that the xylose moiety
      remained unsubstituted at C-2/C-3; exhaustive treatment with chondroitin AC-I
      lyase afforded the fragment delta HexA-Gal-Gal-Xyl-R (R = radio-iodinated
      hydroxyphenyl group), and complete degradations with chondroitin ABC lyase as
      well as testicular hyaluronidase yielded the fragments delta HexA/HexA-GalNAc
      GlcA-Gal-Gal-Xyl-R with or without sulfate on the N-acetylgalactosamine. Partial
      digestions with testicular hyaluronidase or chondroitin B lyase indicated that
      glucuronic acid was common in the first three repeats after the linkage region
      and that iduronic acid could occupy any position thereafter. Hence, there were no
      indications of a repeated, periodic appearance of the clustered GlcA-GalNAc
      repeats which was previously observed in proteoglycan derived dermatan sulfate
      [Fransson L-A, Havsmark B, Silverberg I (1990) Biochem J 269:381-8], suggesting a
      role for the protein part in controlling the formation of particular copolymeric
      features during glycosaminoglycan assembly.

PMID- 1392566
TI  - Application of 2D and 3D NMR experiments to the conformational study of a
      diantennary oligosaccharide.
AB  - By the application of homonuclear 3D NOE-HOHAHA and heteronuclear 3D HMQC-NOE
      experiments in studies of complex oligosaccharides, NOEs can be investigated
      which are hidden in conventional 2D NOE spectra. In the 3D NOE-HOHAHA spectrum
      omega 3 cross sections were considered to be the most suitable for assignment of
      NOEs. Alternatively, these cross sections could be measured separately in
      selective 2D HOHAHA-NOE spectroscopy. The advantages and limitations of the 2D
      alternative are compared with those of the 3D NOE-HOHAHA approach. In 3D HMQC-NOE
      spectroscopy the larger chemical shift displacement of the carbon spectrum with
      respect to the proton spectrum can be used to unmask NOEs hidden in the bulk
      region. If the extra proton dimension is not needed, 2D HMQC-NOE is a good
      alternative. The suitability of 2D and 3D NOE-HOHAHA and HMQC-NOE experiments for
      the estimation of proton-proton distances is demonstrated by comparing the
      results of these experiments on a diantennary asparagine-linked oligosaccharide
      with those of a conventional 2D NOE experiment. NOEs identified in the 2D and 3D
      NOE-HOHAHA as well as HMQC-NOE experiments, so far not identified or not
      quantified in 2D NOE experiments, are discussed in relation to each glycosidic
      linkage. The flexibility of the Man alpha (1-3)Man linkage is demonstrated,
      confirming the existence of an ensemble of conformations for this linkage.

PMID- 1392567
TI  - Positive theta-angles in proteins by nuclear magnetic resonance spectroscopy.
AB  - Non-glycine residues with positive theta-angles have been identified in four
      proteins, barley serine proteinase inhibitor CI-2, bacterial ribonuclease
      (barnase) of Bacillus amyloliquefaciens, hen egg white lysozyme and a basic
      protein from barley seed (barwin) by use of nuclear magnetic resonance
      spectroscopy. By accurate measurements of the coupling constant (3)JHNHalpha and
      integration of the nuclear Overhauser HN-Halpha cross peak, positive theta-angles
      could be determined reliably to 60 degrees +/- 30 degrees, in full agreement with
      the crystal structures for lysozyme, barnase and serine proteinase inhibitor CI
      2. The work emphasizes that positive theta-angles can also occur in non-glycine
      residues and in the four proteins, positive theta-angles have been observed for
      the residue types aspartic acid, asparagine, arginine, serine, glutamine,
      histidine, tyrosine, tryptophan and phenylalanine. The measured (3)JHNHalpha
      coupling constants and the intensity of the intraresidue HN-Halpha NOEs agree
      well with the solution structures of three of the proteins, using the existing
      parametrization of the Karplus curve (Pardi, A., Billeter, M. and Wuthrich, K.
      (1984) J. Mol. Biol., 180, 741-751; Ludvigsen, S. Andersen, K.V. and Poulsen,
      F.M. (1991) J Mol. Biol., 217, 731-736).

PMID- 1392568
TI  - Two-dimensional 1H NMR study of recombinant insect defensin A in water: resonance
      assignments, secondary structure and global folding.
AB  - A 500 MHz 2D 1H NMR study of recombinant insect defensin A is reported. This
      defense protein of 40 residues contains 3 disulfide bridges, is positively
      charged and exhibits antibacterial properties. 2D NMR maps of recombinant
      defensin A were fully assigned and secondary structure elements were localized.
      The set of NOE connectivities, 3JNH-alpha H coupling constants as well as 1H/2H
      exchange rates and delta delta/delta T temperature coefficients of NH protons
      strongly support the existence of an alpha-helix (residues 14-24) and of an
      antiparallel beta-sheet (residues 27-40). Models of the backbone folding were
      generated by using the DISMAN program and energy refined by using the AMBER
      program. This was done on the basis of: (i) 133 selected NOEs, (ii) 21 dihedral
      restraints from 3JNH-alpha H coupling constants, (iii) 12 hydrogen bonds mostly
      deduced from 1H/2H exchange rates or temperature coefficients, in addition to 9
      initial disulfide bridge covalent constraints. The two secondary structure
      elements and the two bends connecting them involve approximately 70% of the total
      number of residues, which impose some stability in the C-terminal part of the
      molecule. The remaining N-terminal fragment forms a less well defined loop. This
      spatial organization, in which a beta-sheet is linked to an alpha-helix by two
      disulfide bridges and to a large loop by a third disulfide bridge, is rather
      similar to that found in scorpion charybdotoxin and seems to be partly present in
      several invertebrate toxins.

PMID- 1392569
TI  - Precise vicinal coupling constants 3JHN alpha in proteins from nonlinear fits of
      J-modulated [15N,1H]-COSY experiments.
AB  - Improved experimental schemes for the recently introduced J-modulated [15N,1H]
      correlation experiment for measurements of the homonuclear amide proton-C alpha
      proton vicinal coupling constants, 3JHN alpha, in uniformly 15N-labeled proteins
      are described, and a nonlinear fit procedure is presented for quantitative
      evaluation of 3JHN alpha. The method was first tested with the N-terminal DNA
      binding domain of the 434 repressor (M = 7.3 kDa), where at 13 degrees C precise
      values of 3JHN alpha in the range 2.0-9.5 Hz were obtained for all residues with
      resolved 15N-1H cross peaks. It was then applied to the Antennapedia homeodomain
      complexed to a synthetic 14-base pair DNA fragment (molecular weight of the
      complex approximately 18 kDa). The 3JHN alpha values measured were found to be in
      excellent agreement with those predicted from the secondary structure of this
      protein in the complex.

PMID- 1392570
TI  - Structure and conformation in solution of the parallel-stranded hybrid alpha
      d(CGCAATTCGC).beta-d(GCGTTAAGCG) by high-resolution 2D NMR.
AB  - The unnatural duplex oligonucleotide alpha-d(CGCAATTCGC).beta-d(GCGTTAAGCG) was
      analyzed by high-resolution NMR methods. All of the exchangeable imino and
      nonexchangeable protons of the duplex were assigned. Detection of all 10 of the
      exchangeable imino protons confirms that a parallel, unsymmetrical duplex is
      formed. The thermal stability of the parallel duplex is similar to the analogous
      antiparallel beta-beta duplex. The right handedness of the helix is confirmed by
      inter-residue [H8/H6-H1'] and [H8/H6-H2"] NOEs to the 5'-neighbor in the beta
      strand and [H8/H6-H1'] NOEs to the 3'-neighbor in the alpha-strand. Intra-residue
      and inter-residue distances between base protons and deoxyribose protons in both
      strands were determined using the isolated spin-pair approximation for NOESY
      cross peaks acquired with mixing times 50 ms or less. The NOE data are consistent
      with a B-form geometry adopted by the alpha/beta hybrid decamer.

PMID- 1392571
TI  - Epidemiology of pediatric brain tumors.
AB  - Brain tumor research is unlike some other areas of cancer research, in which
      definite causes have been identified and prevention and treatment strategies may
      be developed. Primary brain tumors are heterogeneous with respect to several
      characteristics, and brain tumor research is hampered by this fact, as well as by
      the small numbers of cases, by the lack of a clearly established and consistently
      applied histopathologic classification scheme, and by geographical variations in
      diagnostic capabilities and mechanisms for case reporting. The current movement
      toward molecular epidemiology has resulted in several changes in the ways we will
      be able to investigate cancer etiologies in the future, and promises to be
      especially fruitful in the area of brain tumor research. The search is under way
      for biologic markers of risk exposures for various cancers, and for laboratory
      methods to identify those individuals who, because of their genetic qualities,
      are most likely to have brain tumors. There are probably multiple causes for
      brain tumors, incorporating both genetic and environmental pathways. Prior
      research has consistently identified few risk factors for brain tumors, such as
      ionizing radiation. Thus, collaborative efforts among clinicians, laboratory
      scientists, and epidemiologists, which make use of molecular epidemiologic
      methods, are perhaps of greater importance in this field than for cancers arising
      at other sites.

PMID- 1392572
TI  - Pediatric neuro-oncology.

PMID- 1392573
TI  - Neuroimaging of pediatric brain tumors.
AB  - This article covers techniques of imaging, posterior fossa tumors, and
      supratentorial tumors. Computed tomography and magnetic resonance imaging are
      commonly used in the diagnosis and evaluation of pediatric brain tumors. MR
      imaging is the primary imaging technique because it is more sensitive in the
      detection of small tumors, particularly those in the posterior fossa.

PMID- 1392574
TI  - Neurofibromatosis and central nervous system tumors in childhood.
AB  - Neurofibromatosis is a multifaceted disease that often results in tumors of the
      central nervous system. As our understanding of the molecular biology of the
      disease improves along with better neuroradiology imaging, surgical
      instrumentation, and adjunctive care, the management schemes for these patients
      are evolving. This article reviews what is known about neurofibromatosis, common
      management problems with respect to the central nervous system, and an approach
      to the handling of these issues.

PMID- 1392575
TI  - Infant brain tumors.
AB  - This article describes the histology and location of brain tumors in young
      children as well as the presenting features of tumors in this age group and then
      focuses on three tumor types: medulloblastoma, ependymoma, and chiasmatic optic
      glioma. The discussion proceeds in terms of prognosis, late effects of treatment,
      and current and future strategies for treatment.

PMID- 1392576
TI  - Management of optic pathway tumors of childhood.

PMID- 1392577
TI  - Suprasellar and sellar tumors in childhood and adolescence.
AB  - Suprasellar and sellar region tumors in children constitute a diverse group of
      lesions. We advocate an aggressive surgical approach to these tumors for
      diagnostic and therapeutic purposes. With detailed knowledge of the
      microneurosurgical anatomy of this region, the neurosurgeon can choose from a
      number of operative approaches on the basis of tumor size and location. The
      benefits of radiation therapy for craniopharyngiomas and optic
      chiasmatic/hypothalamic tumors must be carefully weighted against the substantial
      long-term risks associated with irradiation of the developing brain in this
      region. During the next decade, the role of primary chemotherapy for germinoma
      and adjuvant chemotherapy for optic pathway gliomas will be determined. Also, the
      role of stereotactic radiation therapy, of great value to some children with
      recalcitrant tumors in the suprasellar region, may be better defined.

PMID- 1392578
TI  - Midline supratentorial tumors.
AB  - Tumors of the supratentorial midline are common in children and are often
      amenable to an aggressive operative resection. MR imaging is invaluable to
      planning an operative strategy. A variety of surgical corridors provide access to
      the deep midline structures, notably the transcallosal, transventricular, and
      basal routes. The histology is important in determining the value of adjuvant
      treatments, such as radiation therapy and chemotherapy. These complex tumors are
      best managed by a multidisciplinary group with a special interest in pediatric
      neuro-oncology.

PMID- 1392579
TI  - Cerebral hemispheric tumors of childhood.

PMID- 1392581
TI  - Brainstem gliomas.
AB  - Brainstem gliomas, a relatively common form of childhood brain tumor, are highly
      resistant to therapy. With computed tomography and magnetic resonance imaging,
      these lesions can be diagnosed with a high degree of reliability. The indications
      for surgery are unclear. Focal lesions may be amenable to partial resections.
      Stereotactic approaches can be used for diffuse lesions, but it has not been
      shown that the information obtained changes the approach to treatment or outcome.
      Higher dose radiotherapy has been recently used but has not improved survival for
      most patients. Patients with brainstem gliomas must be stratified into risk
      groups, and new means of treatment are needed.

PMID- 1392580
TI  - Pineal tumors.
AB  - Tissue diagnosis is necessary for optimal treatment of pineal region tumors in
      children. Preoperative staging should include craniospinal MR imaging with and
      without gadolinium DTPA enhancement, CSF sampling for cytology, and measurement
      of biologic tumor markers in serum and CSF. Surgical approach is determined by
      results of preoperative MR imaging and the extent of resection by the results of
      staging and intraoperative frozen-section histopathologic evaluation. There is no
      longer a role for the radiation test dose (2000 cGy) in the management of these
      tumors. Postoperative treatment is based on histopathology and extent of disease.
      Benign tumors are treated with surgery only, and nondisseminating focal tumors
      with surgery and focal radiation therapy. Non-germinoma malignant germ cell
      tumors are best treated with neoadjuvant chemotherapy followed by radiation
      therapy given focally for focal disease; craniospinal radiation therapy is
      reserved for patients with evidence of disseminated disease at the completion of
      induction chemotherapy.

PMID- 1392582
TI  - Posterior fossa tumors.
AB  - Cerebellar and fourth ventricle tumors are usually associated with hydrocephalus,
      which is now treated with ventriculostomy and tumor removal so that permanent
      shunts are needed in only one third of children. Complete removals decrease the
      recurrence rate of cerebellar astrocytomas and ependymomas. Postoperative staging
      with spinal magnetic resonance imaging has decreased the need for myelography.
      Adjuvant chemotherapy improves the survival of children with high-stage
      medulloblastomas.

PMID- 1392583
TI  - Pediatric skull, skull base, and meningeal tumors.
AB  - Calvarial neoplastic and non-neoplastic tumors are routinely encountered by all
      neurosurgeons. Benign and malignant skull base and meningeal tumors are
      relatively rare lesions in children. Interdisciplinary approaches to those tumors
      more frequently encountered in the pediatric population in these locations are
      discussed. Unique aspects of the diagnosis, treatment, and prognosis for infants
      and children are discussed.

PMID- 1392584
TI  - Spinal cord compression by epidural tumors in childhood.
AB  - Epidural malignancy is the most common cause of nontraumatic spinal cord
      compression in children. Many different tumors may cause compression, either at
      presentation or sometime during treatment. Treatment options include surgery,
      irradiation, and chemotherapy. The decision as to the correct option depends on
      the tumor type and the degree of compression present.

PMID- 1392585
TI  - Intramedullary spinal cord tumors in children.
AB  - Intramedullary spinal cord tumors are uncommon in children, and delayed diagnosis
      is common. Unlike the situation in adults, low-grade astrocytomas predominate
      followed by ependymomas and other gliomas. Recent technological advances,
      including MR imaging, intraoperative ultrasonography, the ultrasonic surgical
      aspirator, and the operative laser, have made radical resection of intramedullary
      tumors feasible. The long-term results of modern-day surgery using these
      techniques are only now becoming available, and the role of adjuvant radiotherapy
      or chemotherapy for the usual low-grade tumors remains unclear. The risk of
      spinal deformity after laminectomy in children and the effects of radiotherapy on
      the growing spine create special challenges in the treatment of pediatric
      intramedullary tumors.

PMID- 1392587
TI  - Long-term effects of treatment for childhood brain tumors.
AB  - Recent studies have recognized brain tumor to be the most important solid
      malignancy in childhood. Improved diagnostic methods and advances in surgical
      technology and instrumentation have significantly lowered operative mortality,
      facilitating more precise and radical surgical resections.

PMID- 1392586
TI  - Pediatric spinal axis tumors.
AB  - Pediatric spinal cord tumors occur in the intramedullary or extramedullary
      spaces. The extramedullary tumors are further divided into those in intradural
      extramedullary or extradural locations. Tumors in the intradural-extramedullary
      region include nerve sheath tumors, meningiomas, and "embryonal" tumors. In the
      extradural space are neuroblastomas, sarcomas, and other primary tumors of bone.
      The radiographic findings, histology, and management of each type of tumor are
      included in this article, which focuses on extramedullary tumors.

PMID- 1392588
TI  - Cutinase is not required for fungal pathogenicity on pea.
AB  - Cutinase, a fungal extracellular esterase, has been proposed to be crucial in the
      early events of plant infection by many pathogenic fungi. To test the long
      standing hypothesis that cutinase of Nectria haematococca (Fusarium solani f sp
      pisi) is essential to pathogenicity, we constructed cutinase-deficient mutants by
      transformation-mediated gene disruption of the single cutinase gene of a highly
      virulent N. haematococca strain. Four independent mutants were obtained lacking a
      functional cutinase gene, as confirmed by gel blot analyses and enzyme assays.
      Bioassays of the cutinase-deficient strains showed no difference in pathogenicity
      and virulence on pea compared to the wild type and a control transformant. We
      conclude that the cutinase of N. haematococca is not essential for the infection
      of pea.

PMID- 1392589
TI  - Acquired resistance in Arabidopsis.
AB  - Acquired resistance is an important component of the complex disease resistance
      mechanism in plants, which can result from either pathogen infection or treatment
      with synthetic, resistance-inducing compounds. In this study, Arabidopsis, a
      tractable genetic system, is shown to develop resistance to a bacterial and a
      fungal pathogen following 2,6-dichloroisonicotinic acid (INA) treatment. Three
      proteins that accumulated to high levels in the apoplast in response to INA
      treatment were purified and characterized. Expression of the genes corresponding
      to these proteins was induced by INA, pathogen infection, and salicylic acid, the
      latter being a putative endogenous signal for acquired resistance. Arabidopsis
      should serve as a genetic model for studies of this type of immune response in
      plants.

PMID- 1392590
TI  - Opaque-2 is a transcriptional activator that recognizes a specific target site in
      22-kD zein genes.
AB  - opaque-2 (o2) is a regulatory locus in maize that plays an essential role in
      controlling the expression of genes encoding the 22-kD zein proteins. Through
      DNase I footprinting and DNA binding analyses, we have identified the binding
      site for the O2 protein (O2) in the promoter of 22-kD zein genes. The sequence in
      the 22-kD zein gene promoter that is recognized by O2 is similar to the target
      site recognized by other "basic/leucine zipper" (bZIP) proteins in that it
      contains an ACGT core that is necessary for DNA binding. The site is located in
      the -300 region relative to the translation start and lies about 20 bp downstream
      of the highly conserved zein gene sequence motif known as the "prolamin box."
      Employing gel mobility shift assays, we used O2 antibodies and nuclear extracts
      from an o2 null mutant to demonstrate that the O2 protein in maize endosperm
      nuclei recognizes the target site in the zein gene promoter. Mobility shift
      assays using nuclear proteins from an o2 null mutant indicated that other
      endosperm proteins in addition to O2 can bind the O2 target site and that O2 may
      be associated with one of these proteins. We also demonstrated that in yeast
      cells the O2 protein can activate expression of a lacZ gene containing a multimer
      of the O2 target sequence as part of its promoter, thus confirming its role as a
      transcriptional activator. A computer-assisted search indicated that the O2
      target site is not present in the promoters of zein genes other than those of the
      22-kD class. These data suggest a likely explanation at the molecular level for
      the differential effect of o2 mutations on expression of certain members of the
      zein gene family.

PMID- 1392591
TI  - Mutations of the 22- and 27-kD zein promoters affect transactivation by the
      Opaque-2 protein.
AB  - By utilizing a homologous transient expression system, we have demonstrated that
      the Opaque-2 (O2) gene product O2 confers positive trans-regulation on a 22-kD
      zein promoter. This trans-acting function of the O2 protein is mediated by its
      sequence-specific binding to a cis element (the O2 target site) present in the 22
      kD zein promoter. A multimer of a 32-bp promoter fragment containing this O2
      target site confers transactivation by O2. A single nucleotide substitution in
      the O2 target sequence not only abolishes O2 binding in vitro, but also its
      response to transactivation by O2 in vivo. We have also demonstrated that an
      amino acid domain including the contiguous basic region and the heptameric
      leucine repeat is essential for the trans-acting function of the O2 protein.
      Similar but not identical O2 target sequence motifs can be found in the promoters
      of zein genes of different molecular weight classes. Conversion of such a motif
      in the 27-kD zein promoter to an exact O2 target sequence by site-directed
      mutagenesis was sufficient to increase the binding affinity of the O2 protein in
      vitro and to confer transactivation by O2 in vivo.

PMID- 1392592
TI  - Two anthranilate synthase genes in Arabidopsis: defense-related regulation of the
      tryptophan pathway.
AB  - Arabidopsis thaliana has two genes, ASA1 and ASA2, encoding the alpha subunit of
      anthranilate synthase, the enzyme catalyzing the first reaction in the tryptophan
      biosynthetic pathway. As a branchpoint enzyme in aromatic amino acid
      biosynthesis, anthranilate synthase has an important regulatory role. The
      sequences of the plant genes are homologous to their microbial counterparts. Both
      predicted proteins have putative chloroplast transit peptides at their amino
      termini and conserved amino acids involved in feedback inhibition by tryptophan.
      ASA1 and ASA2 cDNAs complement anthranilate synthase alpha subunit mutations in
      the yeast Saccharomyces cerevisiae and in Escherichia coli, confirming that both
      genes encode functional anthranilate synthase proteins. The distributions of ASA1
      and ASA2 mRNAs in various parts of Arabidopsis plants are overlapping but
      nonidentical, and ASA1 mRNA is approximately 10 times more abundant in whole
      plants. Whereas ASA2 is expressed at a constitutive basal level, ASA1 is induced
      by wounding and bacterial pathogen infiltration, suggesting a novel role for ASA1
      in the production of tryptophan pathway metabolites as part of an Arabidopsis
      defense response. Regulation of key steps in aromatic amino acid biosynthesis in
      Arabidopsis appears to involve differential expression of duplicated genes.

PMID- 1392593
TI  - A single amino acid substitution in the coat protein of cucumber mosaic virus
      induces chlorosis in tobacco.
AB  - Some strains of cucumber mosaic virus (CMV) induce a bright yellow/white
      chlorosis in tobacco instead of the light green/dark green mosaic induced by most
      CMV strains. This property is controlled by RNA 3 of this tripartite virus.
      Recombination between cDNA clones of RNA 3 from a green mosaic strain, Fny-CMV,
      and a chlorotic strain, M-CMV, and inoculation of infectious transcripts of the
      chimeric RNAs 3, together with RNAs 1 and 2 of Fny-CMV, localized the chlorosis
      induction domain to a region of the coat protein gene containing two nucleotide
      differences. Site-directed mutagenesis of one nucleotide to change the codon for
      Leu129 in the M-CMV coat protein to Pro129 of Fny-CMV changed the phenotype from
      chlorotic to green mosaic, whereas the opposite change in phenotype was observed
      when the Pro129 in the Fny-CMV coat protein was altered to Ser129. Thus, the
      local secondary structure surrounding amino acid 129 rather than a particular
      amino acid per se is involved in chlorosis induction.

PMID- 1392594
TI  - Premature dissolution of the microsporocyte callose wall causes male sterility in
      transgenic tobacco.
AB  - Male sterility in a petunia cytoplasmic male sterile line has been attributed to
      the early appearance of active callase, a beta-1,3-glucanase, in the anther
      locule. This leads to premature dissolution of the callose walls surrounding the
      microsporogenous cells. We have mimicked this aspect of the petunia line in
      transgenic tobacco by engineering the secretion of a modified pathogenesis
      related vacuolar beta-1,3-glucanase from the tapetum prior to the appearance of
      callase activity in the locule. Plants expressing the modified glucanase from
      tapetum-specific promoters exhibited reduced male fertility, ranging from
      complete to partial male sterility. Callose appearance and distribution are
      normal in the male sterile transgenic plants up to prophase I, whereupon callose
      is prematurely degraded. Meiosis and cell division occur normally. The resultant
      microspores have an abnormally thin cell wall that lacks sculpturing. The tapetum
      shows hypertrophy. Male sterility is probably caused by bursting of the aberrant
      microspores at a time corresponding to microspore release. These results
      demonstrate that premature callose degradation is sufficient to cause male
      sterility and suggest that callose is essential for the formation of a normal
      microspore cell wall.

PMID- 1392595
TI  - A novel light-regulated promoter is conserved in cereal and dicot chloroplasts.
AB  - The chloroplast psbD-psbC genes encode D2 and cp43, a reaction center protein and
      chlorophyll-binding antenna protein of photosystem II, respectively. We have
      previously shown that differential accumulation of light-induced psbD-psbC mRNAs
      in barley chloroplasts is due to transcription from a blue light-responsive
      promoter (LRP). It is hypothesized that the light-induced mRNAs help to maintain
      levels of the D2 polypeptide, which is photodamaged and degraded in illuminated
      plants. To determine if light-induced accumulation of psbD-psbC mRNAs was a
      conserved phenomenon in chloroplasts, the expression of psbD-psbC operons from
      five cereals (barley, wheat, rice, maize, and sorghum) and three dicot (tobacco,
      spinach, and pea) species was examined. Cereal and dicot psbD-psbC operons differ
      due to several DNA rearrangements that moved psbK-psbI proximal to psbD-psbC,
      allowing cotranscription of these genes and production of several unique
      transcripts in cereals. Despite differences in the structure and expression of
      the cereal and dicot psbD-psbC operons, the accumulation of light-induced psbD
      psbC mRNAs was conserved in all species studied. An unusual feature of the light
      induced mRNAs was the occurrence of 5' end microheterogeneity. The multiple 5'
      termini were mapped to several consecutive nucleotides (8 to 25 bp) within a
      highly conserved (61%) DNA region that represents the transcription initiation
      site for the mRNAs in barley and tobacco. The novel LRP differs in sequence from
      typical plastid promoters that have prokaryotic "-10" and "-35" elements and is
      centered 570 bp (cereals), 900 bp (tobacco, spinach), or 1100 bp (pea) upstream
      from the psbD translational start codon. We propose that physiological and gene
      regulatory demands of the chloroplast act as constraints that preserved the
      linkage of the LRP with psbD despite DNA inversions involving the psbD upstream
      region.

PMID- 1392596
TI  - Sequence-specific interaction with the viral AL1 protein identifies a geminivirus
      DNA replication origin.
AB  - The bipartite geminiviruses such as tomato golden mosaic virus (TGMV) and squash
      leaf curl virus (SqLCV) have two single-stranded circular genomic DNAs, the A and
      B components, thought to be replicated from double-stranded circular DNA
      intermediates. Although it has been presumed that the origin sequences for viral
      replication are located in the highly conserved 200-nucleotide common region (CR)
      present in both genomic components and that the viral-encoded AL1 protein
      interacts with these sequences to effect replication, there has been no evidence
      that this is in fact so. We have investigated these questions, demonstrating
      selectivity and sequence specificity in this protein-DNA interaction. Simple
      component switching between the DNAs of TGMV and SqLCV and analysis of
      replication in leaf discs showed that whereas the A components of both TGMV and
      SqLCV promote their own replication and that of their cognate B component,
      neither replicates the noncognate B component. Furthermore, using an in vivo
      functional replication assay, we found that cloned viral CR sequences function as
      a replication origin and direct the replication of nonviral sequences in the
      presence of AL1, with both circular single-stranded and double-stranded DNA being
      synthesized. Finally, by the creation of chimeric viral CRs and specific
      subfragments of the viral CR, we demonstrated sequence-specific recognition of
      the replication origin by the AL1 protein, thereby localizing the origin to an
      approximately 90-nucleotide segment in the AL1 proximal side of the CR that
      includes the conserved geminiviral stem-loop structure and approximately 60
      nucleotides of 5' upstream sequence. By deletional analysis, we further
      demonstrated that the conserved stem-loop structure is essential for replication.
      These studies identify the functional viral origin of replication within the CR,
      demonstrating that sequence-specific recognition of this origin by the AL1
      protein is required for replication.

PMID- 1392597
TI  - A tobacco DNA binding protein that interacts with a light-responsive box II
      element.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase plays a key role in
      photosynthetic carbon fixation in higher plants. The small subunit of this
      chloroplast enzyme (rbcS), encoded by a family of nuclear genes, is regulated at
      the transcriptional level by light. Promoter analyses have previously identified
      the box II sequence as a cis element critical for the light-regulated expression
      of rbcS genes. Nuclear factor GT-1 binds specifically to this element and is one
      of the plant nuclear factors that has been detected and studied in great detail.
      Here we describe the cloning and characterization of a tobacco cDNA encoding a
      protein, designated B2F (Box II Factor), with similar binding specificity and
      mobility in gel retardation assays as nuclear GT-1. Steady state levels of mRNA
      encoding B2F do not appear to be regulated by light; this is consistent with the
      previous observation that nuclear GT-1 activity is present in extracts from both
      light-grown and dark-adapted plants. Sequence comparison with another plant trans
      acting factor, GT-2, which binds to a GT-like element in the rice phytochrome
      promoter, shows striking homology in three putative alpha-helices that may be
      involved in DNA binding.

PMID- 1392598
TI  - Characterization of a gene encoding a DNA binding protein with specificity for a
      light-responsive element.
AB  - The sequence element of box II (GTGTGGTTAATATG) is a regulatory component of a
      light-responsive element present within the upstream region of pea rbcS-3A. The
      nuclear protein GT-1 was defined previously as a DNA binding activity that
      interacts with box II. Here, we describe the isolation and characterization of
      cDNA sequences that encode a DNA binding protein with specificity for this
      element. The recombinant protein, tobacco GT-1a, shows similar sequence
      requirements for DNA binding to nuclear GT-1, as assayed by its ability to
      interact with previously defined 2-bp scanning mutations of box II, and is shown
      to be immunologically related to nuclear GT-1. The predicted structure of the 43
      kD protein derived from the cDNA sequence suggests the presence of a novel helix
      helix-turn-helix (HHTH) motif. Comparison between the predicted protein sequence
      encoded by the tobacco GT-1a cDNA and that of another GT binding protein, rice GT
      2, reveals strong amino acid conservation over the HHTH region; this motif
      appears to be involved in the interaction between the recombinant protein and box
      II. Genomic DNA gel blot analysis indicated the presence of a small gene family
      of related sequences within the tobacco nuclear genome. RNA gel blot analysis of
      tobacco mRNA using the isolated cDNA as a probe showed that transcripts are
      present in several tissues, including both light-grown and dark-adapted leaves.

PMID- 1392600
TI  - The remarkable biology of pollen.

PMID- 1392599
TI  - The use of antisense mRNA to inhibit the tonoplast H+ ATPase in carrot.
AB  - Carrot root cells were transformed with the coding or 5' noncoding regions of the
      carrot vacuolar H+ ATPase A subunit cDNA cloned in the antisense orientation
      behind the cauliflower mosaic virus 35S promoter. Bafilomycin-sensitive ATPase,
      H(+)-pumping, and 14C-O-methyl-glucose uptake activities were specifically
      inhibited in the tonoplast fractions of mutant cell lines. Protein gel blotting
      confirmed that the expression of the A subunit was inhibited in the tonoplast
      fraction, but not in the Golgi fraction. Two-dimensional protein gel blots of
      total microsomes of wild-type and control transformant cell lines revealed two
      major immunoreactive polypeptides in the acidic pI range. In contrast, highly
      purified tonoplast membranes contained only the less acidic polypeptide. Because
      the less acidic polypeptide was preferentially diminished in the two antisense
      cell lines, we infer that the antisense constructs specifically blocked
      expression of a tonoplast-specific isoform of the V-ATPase A subunit in carrot.
      Regenerated plants containing the antisense constructs exhibited altered leaf
      morphologies and reduced cell expansion. The altered phenotype was correlated
      with the presence of the antisense construct.

PMID- 1392601
TI  - Secondary plasmodesmata are specific sites of localization of the tobacco mosaic
      virus movement protein in transgenic tobacco plants.
AB  - Expression of the tobacco mosaic virus 30-kD movement protein (TMV MP) gene in
      tobacco plants increases the plasmodesmatal size exclusion limit (SEL) 10-fold
      between mesophyll cells in mature leaves. In the present study, we examined the
      structure of plasmodesmata as a function of leaf development. In young leaves of
      30-kD TMV MP transgenic (line 274) and vector control (line 306) plants, almost
      all plasmodesmata were primary in nature. In both plant lines, secondary
      plasmodesmata were formed, in a basipetal pattern, as the leaves underwent
      expansion growth. Ultrastructural and immunolabeling studies demonstrated that in
      line 274 the TMV MP accumulated predominantly in secondary plasmodesmata of
      nonvascular tissues and was associated with a filamentous material. A
      developmental progression was detected in terms of the presence of TMV MP; all
      secondary plasmodesmata in the tip of the fourth leaf contained TMV MP in
      association with the filamentous material. Dye-coupling experiments demonstrated
      that the TMV MP-induced increase in plasmodesmatal SEL could be routinely
      detected in the tip of the fourth leaf, but was restricted to mesophyll and
      bundle sheath cells. These findings are discussed with respect to the structure
      and function of plasmodesmata, particularly those aspects related to virus
      movement.

PMID- 1392602
TI  - Light-independent chlorophyll biosynthesis: involvement of the chloroplast gene
      chlL (frxC).
AB  - The Chlamydomonas reinhardtii chloroplast gene chlL (frxC) is shown to be
      involved in the light-independent conversion of protochlorophyllide to
      chlorophyllide. The polypeptide encoded by chlL contains a striking 53% amino
      acid sequence identity with the bacteriochlorophyll (bch) biosynthesis bchL gene
      product in the photosynthetic bacterium Rhodobacter capsulatus. In a previous
      analysis, we demonstrated that bchL was involved in light-independent
      protochlorophyllide reduction, thereby implicating chlL in light-independent
      protochlorophyllide reduction in photosynthetic eukaryotes. To perform a
      functional/mutational analysis of chlL, we utilized particle gun-mediated
      transformation to disrupt the structural sequence of chlL at its endogenous locus
      in the chloroplast genome of Chlamydomonas. Transformants for which the multicopy
      chloroplast genome was homoplasmic for the disrupted chlL allele exhibit a
      "yellow-in-the-dark" phenotype that we demonstrated to be a result of the dark
      accumulation of protochlorophyllide. The presence of a chlL homolog in distantly
      related bacteria and nonflowering land plants, which are thought to be capable of
      synthesizing chlorophyll in the dark, was also demonstrated by cross
      hybridization analysis. In contrast, we observed no cross-hybridization of a
      probe of chlL to DNA samples from representative angiosperms that require light
      for chlorophyll synthesis, in support of our conclusion that chlL is involved in
      light-independent chlorophyll biosynthesis. The role of chlL in
      protochlorophyllide reduction as well as recent evidence that both light
      independent and light-dependent protochlorophyllide reductases may be of
      bacterial origin are discussed.

PMID- 1392603
TI  - Expression of an outward-rectifying potassium channel from maize mRNA and
      complementary RNA in Xenopus oocytes.
AB  - Injection of Xenopus oocytes with poly(A)+ mRNA isolated from different plants
      (maize, cucumber, and squash) results in the appearance of a voltage- and time
      dependent, potassium-selective, outward current that is similar to the outward
      rectifying potassium current recorded in many higher plant cells. Maize shoots
      were found to be especially enriched in mRNA encoding such activity. A cDNA
      library of maize shoot mRNA was constructed in the vector lambda ZAPII and was
      used to synthesize RNA complementary to the cDNA (cRNA). Injection of the cRNA
      gave rise to an outward-rectifying potassium current with properties similar to
      the currents obtained by poly(A)+ mRNA injection. These results demonstrate that
      higher plant mRNA can be properly translated into a product that produces a
      voltage-regulated potassium channel in the plasma membrane of Xenopus oocytes.
      Thus, Xenopus oocytes can be used as a heterologous expression system for the
      functional identification and isolation of plant ion channel genes as well as for
      the study of structure-function relationship of plant ion channels.

PMID- 1392604
TI  - A rice cab gene promoter contains separate cis-acting elements that regulate
      expression in dicot and monocot plants.
AB  - The major light-harvesting chlorophyll a/b binding proteins of the photosynthetic
      apparatus are encoded by families of nuclear cab genes. The expression of most
      cab genes is tissue specific and photoregulated in angiosperms. In transgenic
      tobacco plants, expression of the reporter gene beta-glucuronidase (GUS) is
      photoregulated and tissue specific from 5' upstream sequences of the rice cab1R
      gene; deletion of sequences upstream from position -170 with respect to the
      transcription start site eliminates the enhanced and photoregulated expression in
      the transgenic plants. Using an in situ transient expression assay, we have
      determined that the sequence OCT-R, an octamer repeat that lies within the -269
      to -170 region of cab1R, is essential for photoregulated expression of the
      chimeric GUS gene in leaf cells of maize and rice but is not required for
      expression in illuminated tobacco leaves. Conversely, box III*- and G-box-like
      sequences found near OCT-R in cab1R are necessary for high-level transient
      expression of the reporter gene in tobacco leaf tissue but are not required for
      transient expression in maize or rice leaves.

PMID- 1392605
TI  - Protein sorting to the vacuolar membrane.
AB  - The vacuolar membrane (tonoplast) of plant cells contains a polytopic integral
      membrane protein with six membrane-spanning domains and cytoplasmically oriented
      amino-terminal and carboxy-terminal domains. This protein, tonoplast intrinsic
      protein (TIP), is a member of the membrane intrinsic protein (MIP) family of
      proteins, a family of channel proteins found in a variety of organisms. In bean
      seeds, alpha-TIP is synthesized on the rough endoplasmic reticulum and its
      transport to the tonoplast is mediated by the secretory system. In this study, we
      report that a polypeptide segment that includes the sixth membrane domain and the
      cytoplasmic tail of 18 amino acids of alpha-TIP is sufficient to target the
      reporter protein phosphinotricine acetyltransferase to the tonoplast of stably
      transformed tobacco cells. To determine if the carboxy-terminal cytoplasmic tail
      of alpha-TIP contains important tonoplast targeting information, a deletion
      construct lacking the 15 carboxy-terminal amino acids was introduced for
      transient expression in tobacco cells; we found that the slightly truncated
      protein still accumulated in the tonoplast. From these results, we concluded that
      a transmembrane domain of a tonoplast protein probably contains sufficient
      information for transport to the tonoplast. Whether such transport occurs by bulk
      flow or involves specific cellular machinery remains to be determined.

PMID- 1392606
TI  - Budding, fission, transport, targeting, fusion--frontiers in secretion research.

PMID- 1392607
TI  - Developmental expression of tobacco pistil-specific genes encoding novel extensin
      like proteins.
AB  - We have sought to identify pistil-specific genes that can be used as molecular
      markers to study pistil development. For this purpose, a cDNA library was
      constructed from poly(A)+ RNA extracted from tobacco stigmas and styles at
      different developmental stages. Differential screening of this library led to the
      isolation of cDNA clones that correspond to genes preferentially or specifically
      expressed in the pistil. Seven of these cDNA clones encode proteins containing
      repetitions of the pentapeptide Ser-Pro4, which is a typical motif found in
      extensins. Unlike extensin genes, the extensin-like genes described here are not
      induced under stress conditions. RNA gel blot hybridizations demonstrated the
      organ-specific expression of the extensin-like genes and their temporal
      regulation during pistil development. After pollination, the transcript levels of
      the pistil-specific extensin-like genes change relative to levels in unpollinated
      pistils. In situ hybridization experiments showed that at least one of these
      pistil-specific genes is specifically expressed in cells of the transmitting
      tissue. The possible roles of the extensin-like proteins in pistils are
      discussed.

PMID- 1392608
TI  - Specific expression of an extensin-like gene in the style of Nicotiana alata.
AB  - cDNAs and corresponding genomic clones encoding a putative proline-rich protein
      (NaPRP3) were isolated from libraries prepared from Nicotiana alata style mRNA
      and genomic DNA. The predicted NaPRP3 protein is structurally similar to extensin
      in containing six copies of the characteristic extensin sequence Ser-Pro4, but
      differs in being smaller (151 residues compared with greater than 300 residues)
      and lacking Tyr residues. In contrast to most extensin genes, the NaPRP3 gene is
      not induced by mechanical wounding, and its expression is restricted to cells of
      the transmitting tract of the style.

PMID- 1392609
TI  - A novel circadian phenotype based on firefly luciferase expression in transgenic
      plants.
AB  - A 320-bp fragment of the Arabidopsis cab2 promoter is sufficient to mediate
      transcriptional regulation by both phytochrome and the circadian clock. We fused
      this promoter fragment to the firefly luciferase (Luc) gene to create a real-time
      reporter for regulated gene expression in intact plants. Cab2::Luc transcript
      accumulated in the expected patterns and luciferase activity was closely
      correlated to cab2::Luc mRNA abundance in both etiolated and green seedlings. The
      concentration of the bulk of luciferase protein did not reflect these patterns
      but maintained a relatively constant level, implying that a post-translational
      mechanism(s) leads to the high-amplitude regulation of luciferase activity. We
      used a low-light video imaging system to establish that luciferase
      bioluminescence in vivo accurately reports the temporal and spatial regulation of
      cab2 transcription in single seedlings. The unique qualities of the firefly
      luciferase system allowed us to monitor regulated gene expression in real time in
      individual multicellular organisms. This noninvasive marker for temporal
      regulation at the molecular level constitutes a circadian phenotype, which may be
      used to isolate mutants in the circadian clock.

PMID- 1392610
TI  - The internal meristem layer (L3) determines floral meristem size and carpel
      number in tomato periclinal chimeras.
AB  - Cell-cell interactions are important during plant development. We have generated
      periclinal chimeras between plants that differ in the number of carpels per
      flower to determine the roles of cells occupying specific positions in the floral
      meristem in determining the number of carpels initiated. Intraspecific chimeras
      were generated between tomato (Lycopersicon esculentum) expressing the mutation
      fasciated, which causes an increased number of floral organs per whorl, and
      tomato wild type for fasciated. Interspecific chimeras were generated between
      tomato and L. peruvianum, which differ in number of carpels per flower. In both
      sets of chimeras, carpel number as well as the size of the floral meristem during
      carpel initiation were not determined by the genotype of cells in the outer two
      layers of the meristem (L1 and L2) but were determined by the genotype of cells
      occupying the inner layer (L3) of the meristem. We concluded from these
      experiments that during floral organ initiation, cells in certain layers of the
      meristem respond to information supplied to them from other cells in the
      meristem.

PMID- 1392611
TI  - The beta subunit of tomato fruit polygalacturonase isoenzyme 1: isolation,
      characterization, and identification of unique structural features.
AB  - We have purified and isolated cDNAs encoding the beta subunit of tomato fruit
      polygalacturonase isoenzyme 1 (PG1), a cell wall protein that associates with,
      and apparently regulates, the catalytic PG2 polypeptides. Expression of the beta
      subunit is fruit specific and temporally separated from the expression of PG2
      during fruit development. The 37- to 39-kD beta subunit is encoded as a 69-kD
      precursor protein containing a signal sequence and two propeptide domains. The
      mature protein is composed almost entirely of the novel 14-amino acid motif
      FTNYGxxGNGGxxx in which many of the phenylalanine residues are post
      translationally modified. The unique structural features of the motif suggest an
      important role in the function of the protein and hence in the activity of PG1.
      The beta subunit may represent a class of bifunctional plant proteins that
      interact both with structural components of the cell wall and catalytic proteins
      to localize and/or regulate metabolic activities within the cell wall.

PMID- 1392613
TI  - Protein expression from an Escherichia coli/Bacillus subtilis multifunctional
      shuttle plasmid with synthetic promoter sequences.
AB  - A plasmid shuttle vector (pSP10) was designed and constructed to simplify
      screening of cloned DNA and to facilitate expression of the protein products. The
      plasmid contained the following features: (i) a selection gene, chloramphenicol
      acetyltransferase; (ii) an indicator gene encoding beta-galactosidase for visual
      identification of colonies containing DNA inserts; (iii) a cloning region
      immediately upstream from the indicator gene; (iv) origins of replication
      recognized by both Escherichia coli and Bacillus subtilis; and (v) a synthetic
      DNA expression control sequence, including -35 and -10 regions, ribosomal binding
      site, and transcriptional and translational start sites. The promoter region is a
      synthetic consensus sequence derived from published B. subtilis promoters. The
      plasmid has been shown to replicate actively in E. coli and B. subtilis and to
      confer chloramphenicol resistance to both hosts. DNA inserted at the cloning
      region inactivates the indicator gene, resulting in white colonies on 5'-bromo-4
      chloro-3-indolyl-beta-D-galactopyranoside plates. beta-Galactosidase has been
      expressed from pSP10 in both E. coli and B. subtilis. A comparison was made of
      the expression levels of beta-galactosidase from the same plasmid which had been
      modified to contain: (i) the synthetic control region, (ii) no promoter region,
      (iii) the synthetic control region cloned in the opposite orientation, or (iv)
      the tac promoter.

PMID- 1392612
TI  - General roles of abscisic and jasmonic acids in gene activation as a result of
      mechanical wounding.
AB  - Exogenous application of abscisic acid (ABA) has been shown to induce a systemic
      pattern of proteinase inhibitor II (pin2) mRNA accumulation identical to that
      induced by mechanical wounding. Evidence is presented that the ABA-specific
      response is not restricted to pin2 genes but appears to be part of a general
      reaction to wound stress. Four other wound-induced, ABA-responsive genes that
      encode two additional proteinase inhibitors, the proteolytic enzyme leucine
      aminopeptidase, and the biosynthetic enzyme threonine deaminase were isolated
      from potato plants. Wounding or treatment with ABA resulted in a pattern of
      accumulation of these mRNAs very similar to that of pin2. ABA-deficient plants
      did not accumulate any of the mRNAs upon wounding, although they showed normal
      levels of expression upon ABA treatment. Also, application of methyl jasmonate
      (MeJA) induced a strong accumulation of these transcripts, both in wild-type and
      in ABA-deficient plants, thus supporting a role for jasmonic acid as an
      intermediate in the signaling pathway that leads from ABA accumulation in
      response to wounding to the transcriptional activation of the genes.

PMID- 1392614
TI  - An import-competent precursor of small subunit of ribulose-1,5-bisphosphate
      carboxylase generated by factor Xa cleavage from a beta-galactosidase fusion
      expressed in Escherichia coli.
AB  - A plasmid-encoding fusion protein interlinked by factor Xa recognition sequence
      between beta-galactosidase and a precursor of the small subunit of wheat ribulose
      1,5-bisphosphate carboxylase has been constructed. The plasmid directed abundant
      synthesis of the fusion protein in Escherichia coli. The recombinant protein was
      accumulated in an aggregated form that was associated with the bacterial
      membranes. A procedure was developed to isolate the fusion protein in a
      relatively pure and soluble form. Bovine factor Xa cleaved the isolated chimera
      to generate the complete chloroplast precursor of the small subunit of ribulose
      1,5-bisphosphate carboxylase from the fused beta-galactosidase. The cleaved
      precursor protein was imported into the isolated chloroplasts and processed to
      yield its mature counterpart.

PMID- 1392615
TI  - Characterization of recombinant antistasin secreted by Saccharomyces cerevisiae.
AB  - Secretion from recombinant yeast was used as a potential source of large
      quantities of the leech protein antistasin (ATS), a potent and highly specific
      inhibitor of the serine protease coagulation factor Xa. Mature recombinant ATS (r
      ATS) is obtained after intracellular cleavage by the yscF protease of the mating
      factor alpha-1 pre-proleader from the fusion protein at the Lys-Arg sequence
      junction. Production levels are relatively low (ca. 1 mg/liter). Purification of
      the secreted product from a complex growth medium involved cell removal by
      microfiltration and diafiltration, cation-exchange capture and concentration on S
      Sepharose Fast Flow, C-4 reverse-phase high-performance liquid chromatography (RP
      HPLC), and HPLC cation-exchange chromatography step, and RP-HPLC concentration
      and desalting. The process was scaled up from the 16- to the 250-liter level with
      a corresponding increase in amount of r-ATS. From the 250-liter fermentation two
      major forms, r-ATS-I and r-ATS-II, distributed approximately 60:40, and a minor
      form, r-ATS-minor (ca. 1% of the purified r-ATS), were characterized. Limited N
      terminal sequence analysis by Edman degradation indicated that r-ATS-I has the
      predicted mature N-terminus starting with Gln, that r-ATS-II is N-terminally
      blocked with pyroglutamate, and that r-ATS-minor is an incompletely processed
      form. RP-HPLC, hydrophilic-interaction HPLC, cation-exchange HPLC analysis, and
      electrophoresis results are consistent with the differences observed by
      sequencing. Preliminary in vitro characterization by intrinsic Ki determination
      for factor Xa inhibition indicated that the yeast r-ATS forms are
      indistinguishable from each other as well as from r-ATS expressed by the insect
      baculovirus host-vector system. Nevertheless, r-ATS-I and r-ATS-II appear less
      potent than insect-derived r-ATS in the activated partial thromboplastin time
      clotting assay. Further characterization indicated that C-terminal cleavage at
      Pro-116 had occurred in r-ATS-I and r-ATS-II as well as oxidation of methionine
      residues to methionine sulfoxide. The possible role of the C-terminus in
      inhibition of the prothrombinase complex is discussed.

PMID- 1392616
TI  - Purification and characterization of a 65-kDa tumor-associated phosphoprotein
      from rat transplantable hepatocellular carcinoma 1682C cell line.
AB  - We have isolated a homogeneous tumor-associated phosphoglycoprotein of about 65
      kDa (p65) by ammonium sulfate precipitation of proteins from conditioned medium
      containing the rat transplantable hepatocellular carcinoma 1682C cell line,
      followed by high-performance liquid chromatography on molecular-sieving and
      phenyl hydrophobic interaction columns. The protein was concentrated in a Rotofor
      isoelectric focusing cell and finally separated by isoelectrofocusing followed by
      SDS--polyacrylamide gel electrophoresis. We achieved a purification of
      approximately 11,000-fold after the Rotofor concentration step. This protein
      migrated as a single band upon electrophoresis in SDS-PAGE and had a pI of 5.8 in
      isoelectrofocusing gels. The carbohydrate content of the blotted
      phosphoglycoprotein was analyzed by probing the blots with biotinylated lectins;
      a positive reaction was detected with concanavalin A, wheat-germ agglutinine, and
      Ricinus communis agglutinine. To confirm the tumor origin of this molecule,
      hepatocellular carcinoma cells were labeled in vivo using [32P]orthophosphate as
      well as [35S]methionine and cell culture medium was analyzed for the presence of
      radioactive band that corresponds with our protein. Phosphoamine acid analysis by
      thin-layer chromatography showed the presence of phosphotyrosine,
      phosphothreonine, and phosphoserine, which was later confirmed by analysis of the
      amino acid composition. Using the method described by Marchalonis and Weltman for
      comparative analysis of protein structure and evolution, we compared the protein
      isolated by us with other tumor markers and proteins showing similar properties
      and found no significant similarities.

PMID- 1392617
TI  - Isolation and purification of a biologically active human platelet-derived growth
      factor BB expressed in Escherichia coli.
AB  - Human platelet-derived growth factor (PDGF) was expressed in Escherichia coli
      from a high-level cytoplasmic expression vector. A cDNA fragment encoding the
      mature form of the human PDGF B chain (hPDGF-B) was cloned into a plasmid under
      transcriptional control of the inducible E. coli Tac promoter. Expression of
      hPDGF-B from the final construct, pTacBIq, is regulated by the lactose repressor
      (LacIq). Upon induction, a polypeptide of approximately 14 kDa that had the same
      molecular mass and immunoreactivity as authentic hPDGF-B was produced. The
      production of recombinant hPDGF-B was significantly increased in an E. coli
      strain (CAG629) defective in expression of the lon protease. Expression of hPDGF
      B in the CAG629 strain accounted for approximately 1% of total cell protein. In
      this system, hPDGF-B is expressed as an insoluble, intracellular protein and can
      readily be obtained in a partially purified form after differential
      centrifugation. Amino acid sequence determination of the purified protein has
      verified that the amino-terminal portion of the recombinant PDGF is correct.
      After renaturation into dimers, the purified recombinant hPDGF is fully
      functional in assays for receptor binding and mitogenesis.

PMID- 1392618
TI  - One-step immunoaffinity purification of complex I subunits from beef heart
      mitochondria.
AB  - Polypeptides of beef heart mitochondrial complex I were isolated from 15 mg of
      solubilized beef heart mitochondria using antibodies immobilized on an agarose
      chromatography column. The preparation was examined by SDS electrophoresis and
      Western blotting using affinity-purified antibodies to complex I and compared to
      beef heart complex I purified according to the conventional method of Hatefi and
      Rieske. There was a high degree of homology between the two preparations as
      judged by SDS-polyacrylamide electrophoresis and by immunoblotting with seven
      affinity-purified antibodies to various complex I subunits. This method could be
      applied to the preparation of complex I subunits from small samples such as human
      muscle biopsy specimens.

PMID- 1392619
TI  - Ferredoxin:NADP oxidoreductase of Cyanophora paradoxa: purification, partial
      characterization, and N-terminal amino acid sequence.
AB  - The ferredoxin:NADP+ oxidoreductase of the protist Cyanophora paradoxa, as a
      descendant of a former symbiotic consortium, an important model organism in view
      of the Endosymbiosis Theory, is the first enzyme purified from a formerly
      original endocytobiont (cyanelle) that is found to be encoded in the nucleus of
      the host. This cyanoplast enzyme was isolated by FPLC (19% yield) and
      characterized with respect to the uv-vis spectrum, pH optimum (pH 9), molecular
      mass of 34 kDa, and an N-terminal amino acid sequence (24 residues). The enzyme
      shows, as known from other organisms, molecular heterogeneity. The N-terminus of
      a further ferredoxin:NADP+ oxidoreductase polypeptide represents a shorter
      sequence missing the first four amino acids of the mature enzyme.

PMID- 1392621
TI  - Expression of the adenovirus E1B 175R protein and its association with membranes
      of Escherichia coli.
AB  - The E1B 175-amino-acid (175R) protein of adenovirus 2 is required for cellular
      transformation of primary cells and establishing cell morphology in lytically
      infected cells. To investigate the biochemical function of this protein, we
      constructed a bacterial expression vector (pKHB1-T) to produce the 175R protein
      in sufficient amounts for purification and biochemical analysis. On the basis of
      DNA sequencing, gel electrophoresis, and immunoblot analysis, the pKHB1-T-encoded
      175R protein appears to be identical to that expressed transiently in mammalian
      or adenovirus-transformed cells. The bacterially produced viral protein was also
      found to be quite stable and without any modifications. Partial purification of
      the pKHB1-T-encoded protein revealed that the majority of its associates with the
      inner membrane of the bacterial cell. This, together with the possibility of the
      175R protein containing an N-terminal amphipathic alpha-helix as a potential
      translocation signal, suggests that there may be a common mechanism of protein
      transport operating in both eucaryotic and procaryotic systems.

PMID- 1392620
TI  - Human mullerian inhibiting substance: enhanced purification imparts biochemical
      stability and restores antiproliferative effects.
AB  - Separation of copurifying protease activity from recombinant human Mullerian
      inhibiting substance (rhMIS) bound to a monoclonal antibody immunoaffinity column
      by a high-salt wash results in cleaner preparations of rhMIS resistant to
      cleavage upon storage. In addition, an inhibitor of rhMIS antiproliferative
      activity is removed. Proteolytic cleavages produced by either a copurifying
      protease or exogenous plasmin occur at residues 229 and 427 but do not abolish
      rhMIS biological activity. This report details the modified immunoaffinity column
      isolation protocol suitable for proteins such as rhMIS and describes the
      biochemical and antiproliferative properties of this protein.

PMID- 1392623
TI  - Chemical and physiological properties of polysucrose, a new marker of intestinal
      permeability to macromolecules.
AB  - To measure intestinal absorption of macromolecules we have developed a new
      technique employing synthetic polysucrose polymers as probe molecules.
      Polysucrose (PS) is water-soluble, nontoxic, resistant to intestinal enzymes,
      spherical and can be produced with a molecular weight distribution that relates
      to the size of many normal food proteins. Normally, a very small fraction of
      large molecules passes the exclusion barrier of the healthy intestine. Thus,
      quantification of resorbed macromolecules requires assays of high sensitivity.
      For detection of PS in various biological fluids, micro-ELISAs have been
      established. PS with a mean molecular weight of 14,700 daltons (PS 15,000) is
      rapidly excreted into the urine. Twenty-one healthy volunteers who orally
      ingested 1 g of this preparation showed a 12-hour urine excretion of 0.018%
      (interquartile range 0.014-0.022).

PMID- 1392622
TI  - Expression of human NAD-dependent methylenetetrahydrofolate dehydrogenase
      methenyltetrahydrofolate cyclohydrolase in Escherichia coli: purification and
      partial characterization.
AB  - NAD-dependent methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate
      cyclohydrolase is a bifunctional enzyme synthesized as a 37-kDa precursor that is
      imported into the mitochondria of embryonic and transformed mammalian cells. The
      cDNA encoding the human bifunctional enzyme was modified to remove nucleotides
      corresponding to the mitochondrial targeting sequence and was subcloned into a
      procaryotic expression vector under the control of the T7 RNA polymerase
      promoter. The soluble dehydrogenase-cyclohydrolase was expressed in Escherichia
      coli at levels up to 150-fold higher than those found in transformed mammalian
      cells. Forms of the recombinant enzyme with one, three, or seven additional amino
      terminal residues were purified to homogeneity and shown to have similar kinetic
      properties. Investigation of the absolute requirement of the enzyme for Mg2+
      using fluorescence quenching indicates that this ion binds in the absence of
      substrates.

PMID- 1392624
TI  - Detection of IgG subclasses with anti-IgE activity in patients with atopic
      diseases.
AB  - Significantly increased levels of IgG anti-IgE were seen in atopic patients as
      compared with controls. A correlation was observed between the levels of anti-IgE
      autoantibodies and serum IgE in the groups of atopic patients studied. No
      significant correlation was found between IgG anti-IgE levels and severity of the
      disease or between IgG subclasses with anti-IgE activity and clinical status.
      Analysis of IgG subclasses with anti-IgE activity showed that IgG1 and IgG4 were
      clearly factors in differentiating the atopics from the controls. IgG2 and IgG3
      anti-IgE levels were not statistically significantly elevated. The lack of these
      autoantibodies may be explained by the presence of immune complexes or the lack
      of specificity of the monoclonal antibodies used in this study. These
      observations have not yet determined whether these autoantibodies and the
      isotypic selection and restriction observed play a role in the dysregulation of
      the immune response and in the evolution towards atopy.

PMID- 1392625
TI  - Increased eosinophil chemotactic activity in bronchial washes obtained from
      patients with asymptomatic allergic alveolitis.
AB  - The chemotactic activities of eosinophils and neutrophils were measured in
      bronchial washes obtained from 6 symptom-free patients with previous extrinsic
      allergic alveolitis and 9 healthy volunteers. An increased chemotactic activity
      was found in the washes obtained from the patients, and the recovery of
      eosinophils was correlated with the eosinophil chemotactic activity, suggesting a
      causal relationship. Chromatography of the fluids obtained suggested that low
      molecular weight compounds were principally responsible for the increased
      chemotactic activity. A mild disturbance of the integrity of the alveolocapillary
      barrier could to some extent add to the explanation of the increased chemotactic
      activity in the washes obtained from the patients.

PMID- 1392626
TI  - Antiasthmatic activity of a novel thromboxane A2 antagonist, S-1452, in guinea
      pigs.
AB  - We examined the effect of a potent thromboxane (Tx) A2 receptor antagonist,
      calcium (1R, 2S, 3S, 4S)-(5Z)-7-(((phenylsulfonyl)amino)bicyclo[2.2.1] hept-2-yl)
      5-heptenoate dihydrate (S-1452), on antigen- and various allergic-spasmogen
      induced contractions of guinea pig lung parenchymal strips and on the increase in
      insufflation pressure, an index of bronchoconstriction, in anesthetized guinea
      pigs. In isolated guinea pig lung parenchymal strips, S-1452 showed competitive
      antagonism of the contractile activity of U-46619, a TxA2 mimetic, with a pA2
      value of 8.9. The compound also inhibited the contraction induced by
      prostaglandin (PG) D2 and PGF2 alpha, but a TxA2 synthetase inhibitor, OKY-046,
      did not. In contrast, both drugs inhibited not only leukotriene (LT) D4-induced
      contraction but also antigen-induced contraction in the presence of a histamine
      antagonist. In anesthetized guinea pigs, oral administration of S-1452 markedly
      inhibited the bronchoconstrictions induced by intravenous injection of U-46619,
      PGD2, PGF2 alpha, LTD4 and platelet-activating factor (PAF) with ED50 values of
      0.006, 0.031, 0.112, 0.033 and 0.115 mg/kg, respectively, but OKY-046 inhibited
      only that by LTD4 and PAF. Additionally, bronchoconstriction following
      intravenous injection of antigen was almost completely suppressed by S-1452 (0.1
      mg/kg) and partially by OKY-046 (300 mg/kg) in passively sensitized guinea pigs
      which were treated with diphenydramine and propranolol. The inhibitory effect of
      S-1452 against U-46619-induced broncho-constriction persisted up to 7 h after
      oral administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1392627
TI  - Long- and short-term variability of airborne bovine epithelial antigen
      concentrations in cowsheds.
AB  - We have previously demonstrated an association between the level of specific
      airborne animal-derived dusts in animal houses and farmers' humoral responses.
      These findings suggested that allergenic dusts may be able to cause a response in
      a concentration-dependent manner. In order to determine the reliability of a
      single measurement for the evaluation of general levels of dust, we studied the
      long- and short-term variability of airborne bovine epithelial antigen (BEA)
      concentrations in cowsheds. It was found that individual cowsheds seem to have
      characteristic levels of BEA in the air; some cowsheds tend to have consistently
      high concentrations of BEA, whereas in other cowsheds BEA concentrations tend to
      be low. Thus, single determinations do appear to reflect the general level of BEA
      in cowsheds. These findings corroborate the previously observed association
      between the levels of airborne-specific dusts based on single determinations and
      farmers' humoral responses.

PMID- 1392628
TI  - [Sonography and prenatal chromosome diagnosis].

PMID- 1392629
TI  - [Misunderstood and correctly understood genetic counseling].

PMID- 1392630
TI  - [Doppler ultrasound images of the uterine artery and uterine involution in normal
      puerperium].
AB  - Serial sonographic studies of the involution of the uterus and Doppler ultrasound
      studies of the uterine artery blood flow were done with a pulsed Doppler
      apparatus on 102 patients with uncomplicated pregnancy, normal vaginal
      develivery, and normal puerperal course on the 2nd and 4th post-partum days and 1
      and 2 months post partum. Length of the uterus, anteroposterior and transversal
      uterine diameter, and diameter of the myometrium on the anterior and posterior
      uterine wall underwent main involution during the 1st month post partum and
      showed only a slight decrease during the 2nd month post partum.
      Systolic/diastolic ratio and resistance index of the uterine artery increased
      slightly, but not significantly, between the 2nd and 4th post-partum days, but
      significantly until the end of the 1st month post partum. Until the end of the
      2nd month post partum systolic/diastolic ratio and resistance index of the
      uterine artery showed, although the involution of the uterus was largely
      completed, a further significant increase.

PMID- 1392631
TI  - [Regulation of sterol carrier protein-2 in human luteal cells by LH and LH-RH].
AB  - Conversion of cholesterol to pregnenolone is the most important and, at the same
      time, the rate-limiting step of steroidogenesis. Sterol carrier protein-2 (SCP2)
      or nonspecific lipid transfer protein (nsL-TP) is an intracellular protein, which
      plays an important role in the pre- and transmitochondrial transport of
      cholesterol and for the mitochondrial synthesis of pregnenolone. Synthesis of
      pregnenolone in rat Leydig cells can be increased by LH and LH-RH; however, only
      LH leads to characteristic changes in intracellular concentrations of SCP2. This
      means that synthesis of pregnenolone is regulated in two different ways. In this
      study we aimed to find out whether such a 'second way' of steroidogenesis is also
      demonstrable for the human corpus luteum (i.e. human luteal cells). Human luteal
      cells were collected during follicle punctures and were cultured as described
      previously. We demonstrate that (human) LH/hCG are able to enhance pregnenolone
      synthesis; this process is accompagnied by typical changes of SCP2 and an
      increase in activity of 7-dehydrocholesterol reductase, which is a marker enzyme
      for SCP2. LH-RH was shown to exert no effect. Thus, we conclude that a second way
      of steroidogenesis (i.e. synthesis of pregnenolone) cannot be proved for the
      human corpus luteum.

PMID- 1392632
TI  - [Prognostic factors in endometrial cancer. A retrospective study based on 564
      patients].
AB  - 564 patients with cancer of the endometrium were treated at the Department of
      Obstetrics and Gynaecology of the University Hospital in Zurich during the years
      1970-1989. The most important clinical and pathologic-anatomic prognostic factors
      were evaluated and compared with the literature in a retrospective study.
      Myometrial depth of infiltration and histological tumour grading could be
      confirmed as reliable prognostic factors. Their influence on survival curves was
      highly significant (log rank test: p = 0.0001). In agreement with other authors
      the prognostic influence of the uterine length is minimal and not significant.
      Therefore the replacement of the criterion uterine-sond length by depth of
      myometrial infiltration in the new FIGO classification of 1989 is justified also
      in view of our data.

PMID- 1392633
TI  - [Effectiveness of estriol depot vaginal suppositories in postmenopausal women
      with urogenital climacteric manifestations].
AB  - In this study, 43 postmenopausal patients with urogenital complaints such as
      vaginal dryness, incontinence, or bleeding with intercourse were treated with
      weekly applications of Orthogynest vaginal estriol suppositories in a new depot
      form. A marked increase in the vaginal epithelium (A. Schmitt score) and a
      significant decrease in symptoms due to vaginal atrophy were noted. The depot
      form allows for decreased dosing frequency, leading to improved compliance.
      Systemic symptoms, such as hot flashes and emotional lability, were also noted to
      respond to the Orthogynest suppositories.

PMID- 1392634
TI  - [Intra-epithelial neoplasia of the vulva and smoking].
AB  - VIN III etiology is multifactorial with a predominant role held by human
      papillomavirus infections, especially infections with HPV type 16. Other
      cofactors are also involved. We reviewed our patients presenting with VIN III,
      focusing our attention on smoking. Out of 37 patients 29 (78%) were smokers and
      among those who presented with a relapse after treatment (11 patients) all were
      smokers. We discuss mechanisms by which tobacco could act as a cofactor in VIN
      III.

PMID- 1392635
TI  - Biological gestational age and its calendar assessment with ultrasound. Part 1:
      Physiological considerations.
AB  - Biological gestational age differs from calendar age, which is only its
      measurement. In spite of that in many countries all over the world, the rule for
      termination of pregnancy exclusively because its calendar duration is longer than
      293 days (so-called postterm pregnancy) is widely applied. Constant increase in
      the blood oxytocinase level of pregnant women, just like the sonographic
      measurements of fetal bodies, proves the appropriate development of pregnancy
      with all the more accuracy, the more similar the subsequent values of the
      enzymatic and ultrasonographic determinations. From medical and ethical points of
      view the 'obstetrical' scale comprising sequential periods' pre-, at- and post
      term' is an incorrect way of calculating the duration of pregnancy. Gynecologists
      have to use the word 'term' only to describe an individual's date of fetal
      maturity (birth-date) and the possible true pre- and post-term of an individual
      should be placed within as well as outside the normal range of deliveries.

PMID- 1392636
TI  - People of color: look out for rickets!

PMID- 1392638
TI  - Physicians who do not want to see the number or the power of midwives in this
      country increase.

PMID- 1392637
TI  - Interview with Merri Morris, M. D.. Interview by Ina May Gaskin.

PMID- 1392640
TI  - Florida celebrates passage of Midwifery Act!

PMID- 1392639
TI  - A new approach is coming to obstetrics: a birth center with everything under one
      roof.

PMID- 1392641
TI  - How to become a midwife in the United States.

PMID- 1392643
TI  - My impressions of the French health care system.

PMID- 1392642
TI  - 20 lessons on how to find and keep physician backup.

PMID- 1392644
TI  - Two partial abruptions in a row.

PMID- 1392645
TI  - Have you ever "midwifed" a birth where no vaginal exams were done?

PMID- 1392646
TI  - Landmark decision for British homebirth & midwifery.

PMID- 1392647
TI  - Interview with Makeda Kamara. Interview by Ina May Gaskin.

PMID- 1392648
TI  - The past and present of the Polish National Health Services. Reform project.
AB  - This paper presents a short historical outline of the national health service
      (NHS) system in Poland. Consecutive stages of the NHS system reform are described
      (up to October 1991), including the period of early 80's and the Round Table
      Conference. The general principles of the project of the Polish NHS system
      reform, which is intended to be implemented with support from the World Bank, are
      presented. These principles are related particularly to the scope of the
      questions assigned to the task forces established to solve the basic problems of
      the present system. Those include: 1. Health Promotion Task Force, 2. Primary
      Health Care Task Force, 3. Occupational Health Task Force, 4. Health Information
      System Task Force, 5. Cost Accounting Task Force, 6. Resource Allocation Task
      Force, 7. Pharmaceutical Monitoring and Drug Control Task Force, 8. Management
      Development Task Force, 9. Regional Health Services (Consortia) Task Force.

PMID- 1392649
TI  - The impact of the chemical industry on the human environment.
AB  - The magnitude of the emitted to the air dusts and gases, liquid and solid wastes
      disposal produced by chemical industry is presented. Impact of chemical industry
      on the environment is discussed. Some hazardous agents, occurring in the work
      environment, morbidity and sickness absenteeism rates, noted among employees in
      chemical industry, are considered.

PMID- 1392650
TI  - Toxic effects of combined exposure to toluene and m-xylene in animals. III.
      Subchronic inhalation study.
AB  - Effects of combined exposure to toluene and m-xylene in the conditions of
      subchronic inhalation experiments in rats were examined. Rats were exposed to
      vapours of individual solvents and their 1:1 mixture at concentrations of 1000
      ppm or 100 ppm, 6 h/day, 5 days/week, for 3 or 6 months, respectively. In rats
      exposed for 3 or 6 months to toluene, m-xylene and their mixtures (1:1) at
      concentrations of 1000 ppm and 100 ppm, respectively, the observed disturbances
      in rotarod performance test and decrease in spontaneous motor activity were
      statistically significant in comparison to control. In animals exposed to
      mixtures (1:1) of toluene and m-xylene, changes were not significantly different
      but more pronounced when compared to single solvent groups. The decrease of red
      blood cells count and increase of rod neutrophil cell counts were observed only
      in rats exposed for 3 months to mixture of solvents. Results obtained in
      condition of acute and subchronic inhalation exposure and toxicokinetics data
      interpreted jointly indicate the more than additive toxic effects of combined
      exposure to toluene and m-xylene.

PMID- 1392651
TI  - The toxic effects of combined exposure to toluene and m-xylene in animals. IV.
      Liver ultrastructure after subchronic inhalatory exposure.
AB  - The effects of combined inhalatory exposure to m-xylene and toluene on the rat
      hepatocytes were investigated. Limited proliferation of smooth endoplasmic
      reticulum and increase of the number of lysosomes were observed in hepatocytes
      after 3-months of single exposure to 1000 ppm of m-xylene and toluene. Moreover,
      mitochondria increased in most of hepatocytes. After combined exposure to mixture
      of m-xylene and toluene at concentrations of 500 + 500 ppm, respectively, the
      types of ultrastructural changes in hepatocytes followed the pattern observed
      after exposure of each of the single organic solvent. However, proliferation of
      the smooth endoplasmic reticulum was more eminent. The hepatocytes ultrastructure
      of rats exposed to 100 ppm of m-xylene and toluene for 6 months were similar to
      that observed in rats exposed to 1000 ppm of m-xylene for 3 months. In rats
      exposed to a mixture of m-xylene and toluene for 6 months, the ultrastructural
      changes in hepatocytes were a combination of those observed after a single
      exposure to each of the organic solvent. It may be concluded that changes in the
      hepatocytes ultrastructure were an adaptive rather than a toxic effect. Because
      in the case of combined exposures the doses were half of those used in single
      exposures, the additive effect on the proliferation of smooth endoplasmic
      reticulum was observed in the rat liver after combined exposure to toluene and m
      xylene using electron microscopy.

PMID- 1392652
TI  - Tolerance to chlorphenvinphos in rats assessed on the basis of changes in
      locomotor behavior in rotating wheels.
AB  - Spontaneous locomotor activity in rotating wheels was investigated in rats
      exposed repeatedly (i.p. daily injections, five days a week for two weeks) to an
      agricultural organophosphorus pesticide, chlorphenvinphos (CVP) at doses of 1.0
      and 3.0 mg/kg. After a seven day interval each rat was injected with a single 3.0
      mg/kg test dose of CVP in order to assess the stability of tolerance. Concomitant
      changes in blood and the brain ChE activity were also investigated. It was found
      that exposure to CVP at a low dose (1.0 mg/kg), resulting in less than 50%
      reduction of ChE activity in blood and in the brain, did not produce changes in
      spontaneous locomotion in rotating wheels in the rat. Higher doses (3.0 mg/kg)
      inhibited blood and the brain ChE by more than 50% and reduced locomotion. Under
      conditions of repeated exposure to CVP at the symptomatic (3.0 mg/kg) dose ChE
      activity remained low throughout the exposure period, however, locomotor activity
      returned to a normal level, i.e. tolerance developed, within less than five days.
      Seven days after termination of the repeated exposure, the behavioral
      subsensitivity to CVP still remained. The biochemical data suggest that it may be
      related, at least partially, to a diminished vulnerability of ChE in some parts
      of the brain to CVP induced inhibition.

PMID- 1392654
TI  - Experimental assessment of the effect of coal dust with polymetallic salts on the
      respiratory tract epithelium.
AB  - Experimental assessment of the effect of coal dust from the Debiensko coal mine
      on the rat respiratory tract epithelium was carried out. The coal mine there
      contains up to 0.6 per cent of polymetallic salts including such heavy metals as
      Co, Cu, Mn, Ni, Pb, Sr, Zn. Inflammation of the upper respiratory tract caused by
      the coal dust was proved as well as mucous membrane ulceration and epithelial
      dysplasia.

PMID- 1392653
TI  - A comparison of changes in spontaneous (EEG) and evoked brain activity induced by
      chlorphenvinphos and physostigmine in rats and rabbits.
AB  - The effects of single i.p. injections of two cholinesterase inhibitors,
      chlorphenvinphos (CVP) and physostigmine, on hippocampal and cortical EEG and
      flash evoked potentials in occipital cortex were compared in rabbits and rats. A
      comprised method of spectral analysis was employed for evaluation of changes in
      EEG. The obtained results showed that in both species the changes in hippocampal
      and cortical EEG after administration of CVP were relatively small or negligible
      in comparison with those after physostigmine administered in doses resulting in
      comparable (or even lesser) inhibition of blood cholinesterase (ChE). Neither CVP
      nor physostigmine resulted in significant changes in the morphology of the flash
      evoked potentials. The data do not confirm the suggestion that brain electrical
      activity is the most sensitive index of neurotoxicity resulting from exposure to
      organophosphate ChE inhibitors.

PMID- 1392656
TI  - Occupational medicine in Polish journals of 1991; Part 1.

PMID- 1392655
TI  - Transformation of field monitoring results into miners' annual exposures to radon
      progeny.
AB  - This paper presents the theory of estimating miners' radiation hazard, using the
      values of radon daughters' concentration in the work-environment. All measurement
      results can be obtained with any technique beginning with instant measurement and
      ending with long-term dosimetry. The measurements carried out in metal ore mines
      show that the seasonal changes in radon daughters' concentration have their main
      influence in the estimation of the miners' hazard. The estimation of the hazard
      which was obtained from equations, was compared with the results given from the
      computer simulation.

PMID- 1392657
TI  - The role of biological markers in toxicology.
AB  - Biological markers are tools that can be used to clarify the relationship,
      between exposure to a xenobiotic compound and health impairment and to indicate
      individual or population differences that affect the biologically effective dose.
      Biological markers, broadly defined, are indicators of variation in cellular or
      biochemical components or processes, structure, or function that are measurable
      in biological systems or samples. There is growing interest in the use of
      biological markers to study the health effects of exposure to environmental
      toxicants in occupational medicine, epidemiology, toxicology, and related
      biomedical fields.

PMID- 1392658
TI  - Comparison of results derived from follow-up examination of respiratory systems
      in chosen groups of metallurgists.
AB  - In a 16.5-year follow-up study of the steel industry we investigated the relation
      of chronic occupational exposure to the changes of ventilatory efficiency and to
      the frequency of chronic bronchitis (Chronic Obstructive Pulmonary Disease--COPD)
      in a group of 65 men working in the harmful environment of a Coking Plant (CP).
      The reference group comprised 34 employees of Cold Rolling Mill (CRM) working in
      favorable hygienic conditions. The faster decline of VC and FEV1 were noted in
      the group of CP in comparison to the control group. Also the frequency of
      pathologic values of RT was significantly higher (p < or = 0.001) in the exposed
      group. The incidence of COPD increased more in the group of CP than in the group
      of rollers. No differences in the annual decline of FEV1 and VC between smokers
      and nonsmokers from CP were noted, while in the group of men working in favorable
      environmental conditions the differences between smoking categories were
      significant. It suggests that the impact of occupational exposure is so powerful
      that it can mask the unfavorable influence of cigarette smoking on the
      ventilatory function of men working in a Coking Plant.

PMID- 1392660
TI  - Biological monitoring of risk of bladder cancer in persons occupationally exposed
      to aromatic amines.
AB  - Recent advances in molecular biology and toxicology have greatly contributed to
      the early diagnosis of biological changes which may evoke neoplasms. This paper
      reviews the issues regarding the screening of persons occupationally exposed to
      carcinogenic aromatic amines. The screening was designed for an early detection
      of bladder cancer by means of biochemical tests. The applied tests facilitated
      the estimation of the level of aromatic amines which penetrate an organism
      (biomarkers of exposure), early diagnosis of the biochemical disorders which may
      influence cancer development (biomarkers of early effects) and the detection of
      genetic predispositions which enhance risk of such disorders (biomarkers of
      susceptibility).

PMID- 1392661
TI  - Effects of underwater noise on human hearing.
AB  - Hearing conservation for divers and swimmers has been overlooked nearly
      everywhere in the world. Because submerging a listener changes his or her
      auditory physiology dramatically, the research upon which we base exposure limits
      for airborne noise is not pertinent under water. Of the research that is
      necessary for developing a damage-risk standard for underwater noise exposure,
      only a negligible amount has been done. The value of Poland's marine industries
      and the motivation of its audiologists make Poland and ideal country in which to
      accomplish this research and to develop the foundation for national and
      international standards.

PMID- 1392659
TI  - Coughing as the sole symptom of occupational bronchial allergy.
AB  - In all of 11 observed patients with bakers' asthma, coughing preceded the
      development of dyspnea. Seventeen coughing atopic patients working in a bakery
      were observed for 2 years and treated with ketotifen and disodium cromoglycate
      (DSCG). Four of the patients developed asthma. Ketotifen prevented coughing
      attacks but did not prevent asthma development. Bronchodilators interrupted cough
      attacks. DSCG was ineffective.

PMID- 1392662
TI  - The effect of maternal exposure to dioxolane on prenatal and postnatal
      development in rats.
AB  - Female rats were given by gavage every other day from days 8-20 of gestation an
      aqueous solution of dioxolane at daily doses equal to 0.025, 0.1 and 0.2 LD50
      (first series--prenatal development) or from days 2-20 of gestation at daily
      doses equal to 0.025, 0.075 and 0.15 LD50 (second series--postnatal development).
      At doses toxic or subtoxic to maternal rats (0.1 and 0.2 LD50) dioxolane did not
      cause increased embryo or fetus intrauterine death rates or congenital defects,
      it did cause, however, dose-related delays in fetal development. Dioxolane does
      not cause impairment of physical development or behavioral disturbances. Exposure
      to higher doses of the compound (0.2 LD50) leads to increased perinatal death
      rates in the offspring, without causing, however, disturbances in the maternal
      instinct. The exposure of pregnant rats to dioxolane decreased haemoglobin levels
      in 5-week-old offspring. At a dose 1.15 g/kg (0.2 LD50) the chemical
      significantly increased exploratory motor activity of female offspring at the age
      of 8 weeks, but did not affect significantly locomotor activity of males and the
      active avoidance acquisition of adult offspring.

PMID- 1392663
TI  - Genotoxicity assessment of sulfosuccinate IO-5, Rokamid MRZ 17, Rokacet RZG7P2
      and Roksol TL-7 using bacteria and bone marrow rodent cells.
AB  - Three short-term tests were used for evaluation of the genotoxic activity of four
      surface active agents. These were: Ames, Salmonella reversion assay using 4
      tester strains (TA97a, TA98, TA100 and TA102), the micronucleus test int the bone
      marrow of Balb C mice and in vivo sister chromatid exchange (SCE) analysis in
      SFIS or Balb C mice. The frequency of micronucleated PCEs did not exceed the
      control values in mice of both sexes after intraperitoneal administration of all
      four compounds. Three preparations--Sulfosuccinate IO-5, Rokamid MRZ 17 and
      Rokacet RZG7P2 produced a negative response in Salmonella strains gene mutation
      assay and SCE induction test in mouse bone marrow cells. The Roksol TL-7 induced
      frameshift and base-pair substitution mutations in Salmonella tester strains both
      with and without S9 (prepared from the liver of rats which had been pretreated
      with Aroclor 1254). Evidently positive results (more than a twofold increase in
      the number of revertants per plate) were observed in tester strain S. typhimurium
      TA97a (with and without S9 metabolic activation) and S. typhimurium TA100 (with
      S9 metabolic activation) at a dose of 0.2 microliter Roksol TL-7 per plate.
      Roksol TL-7 caused slight increase in the SCE level in mouse bone marrow cells. A
      significant increase in SCE frequency was observed at doses of 50, 75 and 100
      mg/kg.

PMID- 1392664
TI  - Occupational medicine in Polish journals of 1991; Part 2.

PMID- 1392665
TI  - Occupational medicine in the eastern European journals of 1991; Part 1.

PMID- 1392666
TI  - Oral anticoagulant therapy: practical considerations.
AB  - The key to safe and effective oral anticoagulation is to have an understanding of
      the rationale for dosing guidelines and therapeutic ranges; an appreciation of
      the imprecision of prothrombin time testing and its standardization; knowledge of
      the factors influencing prothrombin time response; and awareness of the
      importance of patient empowerment via ongoing patient education. This review
      focuses on the routine management of oral anticoagulant therapy to provide these
      practical insights and to promote safe and effective therapy.

PMID- 1392667
TI  - Anticoagulation during pregnancy.
AB  - When anticoagulants are indicated during pregnancy, the needs of the mother as
      well as those of the fetus must be considered. Although anticoagulants may be
      indicated to prevent life threatening maternal thrombosis, oral anticoagulants
      such as warfarin have been associated with fetal anomalies. Patient education and
      early intervention with carefully monitored subcutaneous heparin can reduce both
      fetal and maternal risks.

PMID- 1392668
TI  - An act of violence.

PMID- 1392669
TI  - Karen Manning: practicing in pediatric cardiology. Interview by Karna Bramble.

PMID- 1392670
TI  - Judicial review of treatment consent issues for minors.

PMID- 1392671
TI  - The regulatory process: impacting the NP's role.

PMID- 1392672
TI  - The role of aspirin in the prevention of cardiovascular and cerebrovascular
      disease.

PMID- 1392673
TI  - Components and defects of the coagulation system.
AB  - The purpose of this review article is to present a simplified view of coagulation
      in five parts (vessels, platelets, cascade, natural inhibitors, and
      fibrinolysis), update the NP with current concepts regarding coagulation, discuss
      cellular and protein functions, and provide an overall understanding of how the
      five components work together. Discussion of disease states, genetic
      deficiencies, and acquired inhibitors of the coagulation system is included in
      this article.

PMID- 1392674
TI  - Acquired hypercoagulable states.
AB  - Acquired hypercoagulable states comprise a diverse group of clinical conditions
      that are associated with an increased risk of thrombosis. These clinical
      conditions include malignancy, diabetes mellitus, venous stasis, pregnancy, oral
      contraceptive use, lupus anticoagulant, postoperative state, immobilization,
      myeloproliferative disorders, and nephrotic syndrome. Recognition of these
      associations, possible underlying mechanisms, identification of high risk
      individuals, thromboembolic prophylaxis, and other clinical implications are
      discussed.

PMID- 1392675
TI  - Inherited hypercoagulable states: questions and controversies.
AB  - Inherited hypercoagulable states such as protein C, protein S, and antithrombin
      III deficiencies account for 15% to 20% of recurrent thromboembolic episodes. A
      common risk profile is associated with these disorders and guides the use of
      laboratory screening. The use of anticoagulants in inherited hypercoagulable
      states varies with a patient's personal and familial history of thrombosis.
      Special consideration is given to the need for anticoagulants perioperatively and
      during pregnancy.

PMID- 1392676
TI  - Oral anticoagulation therapy: indications, contraindications, and complications.
AB  - The goal of oral anticoagulation therapy is to prevent thromboembolic events
      while minimizing the possibility of hemorrhage. This article discusses
      indications for, contraindications to, and possible complications of
      anticoagulant therapy. Guidelines for the use of low intensity and high intensity
      anticoagulation and duration of anticoagulant therapy are also included.

PMID- 1392677
TI  - Factors that influence therapeutic anticoagulation control.
AB  - A wide range of variables can influence warfarin anticoagulation control. This
      report summarizes the effects of medication, alcohol, diet, and other factors on
      prothrombin times. Useful summary tables are included.

PMID- 1392678
TI  - Local anesthesia: a review.
AB  - Local anesthetics are the most widely administered drugs in dentistry.
      Significant advances have been made in past decades that have greatly increased
      both the safety and the efficacy of these important drugs. This paper reviews the
      history of local anesthesia, pharmacokinetics and clinical implications,
      techniques, complications, and future directions in the quest for more effective
      pain control in dentistry.

PMID- 1392679
TI  - Clinical investigation of potency and onset of different lidocaine sprays for
      topical anesthesia in dentistry.
AB  - The clinical effects of three lidocaine-containing solutions with and without
      frigen (freon-113) as a propellant, after different waiting periods, and with
      different dosages applied were investigated in 130 outpatients who were
      undergoing dental treatment in the maxilla under local anesthesia. They were
      divided randomly into five groups (A through E): (A) Xylocaine spray with frigen,
      two applications (20 mg lidocaine); (B) Xylestesin spray with frigen, two
      applications (14 mg lidocaine); (C) Xylestesin spray with frigen, three
      applications (21 mg lidocaine); (D) Xylestesin pump spray without frigen, two
      applications (14 mg lidocaine); and (E) no topical anesthesia. They were further
      divided into 12 subgroups to evaluate waiting periods between the application of
      the topical anesthesia and the injection (1, 2, or 3 minutes). Patients assessed
      the pain of the injection, intensity of numbness, and intensity of the taste on a
      visual analog scale; they also assessed the pain of the injection compared to
      former injections. Pain during injection was reduced by topical application of
      lidocaine. A waiting period of 2 minutes proved to be sufficient and can be
      justified to avoid impatience and increased numbness in patients. However, a 3
      minute waiting period may be appropriate for sensitive patients. An increase in
      the dosage failed to show better analgesia. The pump spray without frigen proved
      to be effective.

PMID- 1392680
TI  - Displacement of the endotracheal tube caused by postural change: evaluation by
      fiberoptic observation.
AB  - Unexpected displacement of the endotracheal tube during anesthesia caused by
      postural change of the neck or passive compression by the mouth gag was
      investigated under transluminal fiberoptic observation. Twenty-two patients were
      divided into orotracheal and nasotracheal intubation groups according to the
      technical requirements of the planned oral and maxillofacial surgery. Under
      nasotracheal intubation, the mean length of displacement from the carina was 21
      mm by extension of the neck, and 8 and 7 mm by lateral rotation of the neck to
      the right and left sides, respectively. Under orotracheal intubation, the mean
      length of displacement from the carina was 12 mm by extension of the neck and
      almost 28 mm with application of the mouth gag. To avoid accidental extubation or
      one-sided bronchial intubation during anesthesia, the tip (distal end) of the
      endotracheal tube should be located less than 32 mm from the carina before
      extension of the neck and more than 41 mm from the carina before application of
      the mouth gag.

PMID- 1392681
TI  - Ingestion and aspiration of foreign bodies.
AB  - Foreign bodies may be swallowed as well as aspirated, but patients and their
      relatives may not understand the distinction. Fortunately, swallowing occurs more
      often than aspiration. Dental prostheses present specific problems in this
      regard. Their configuration impedes easy gliding through the esophagus and makes
      their extraction difficult. Swallowing of foreign bodies in elder patients is
      often explained by a decrease in psychological or neurological function, which
      undoubtedly may occur. The loss of tactile sense of the hard and soft palate as a
      result of complete denture use is another reason for frequent occurrence of this
      problem in elder patients.

PMID- 1392682
TI  - How safe is dental anesthesia?
AB  - In the United Kingdom, the number of general anesthetics given under the National
      Health Service in general dental practice (excluding those given in hospitals)
      has declined steadily during the past 10 years. The mortality rate has also
      declined from approximately 1 in 200,000 (1952) to 1 in 2,000,000 (1990). These
      figures include deaths that occurred following treatment in hospitals and are
      divided almost equally between anesthetics given in hospitals and those given in
      dental practices. This paper examines the causes of deaths under dental general
      anesthesia and evaluates the proposals that have been made by the various
      official bodies appointed to consider the subject.

PMID- 1392683
TI  - Victory over pain: an historical perspective.
AB  - Horace Wells, a dentist, is credited with the discovery of anesthesia. However,
      there are others who experimented with inhalation agents long before Wells' time.
      This paper reviews the history of anesthesia and recounts its discovery by Wells
      in 1844 as we approach the 150th anniversary of the event.

PMID- 1392684
TI  - Practical application of meridian acupuncture treatment for trigeminal neuralgia.
AB  - This report evaluates the effect of meridian acupuncture treatment on trigeminal
      neuralgia. Ten patients aged 26 to 67 years (mean 55.4 years) who visited the
      outpatient Dental Anesthesiology Clinic at Tsurumi University Dental Hospital
      from 1985 to 1990 were studied. Five of the patients suffered from idiopathic and
      five from symptomatic trigeminal neuralgia. The patients underwent meridian
      treatment by acupuncture alone or acupuncture combined with moxibustion. The
      acupuncture method used was primarily basic treatment employing only needles
      without electrical stimulation. Meridian acupuncture treatments were repeated
      from two to four times a month. Five patients were restored to a pain-free state.
      The other five patients noted a decrease in pain, but with some level of pain
      remaining (significant pain in one patient). It is concluded that meridian
      acupuncture treatment is useful and can be one therapeutic approach in the
      management of trigeminal neuralgia.

PMID- 1392685
TI  - The baboon: an ideal model in biomedical research.
AB  - The baboon is a good animal model for research and investigations in physiology
      and pathophysiology, also using radiopharmaceutical techniques. It has several
      similarities to the human being, and all parameters in human physiology can be
      measured in the baboon model with the same or equal technical equipment. Fourier
      phase analysis in radionuclide ventriculography, hemodynamic reactions in a
      septic shock model, and investigations in conjunction with local anesthetics (eg,
      effects on cerebral blood flow) are typical types of research that have been or
      are currently being performed on the baboon. Institutes using the baboon model
      must be equipped with all instruments and operating facilities as would be needed
      for investigations in human beings. Ethical considerations must be regarded
      strictly and supervised by an ethics committee. Protocols must determine exactly
      why in vivo experimentation is preferred to in vitro tests. Anesthesia techniques
      in a baboon model allow study on the animal itself, eliminate pain (and stress)
      to the animal, and should not interfere with the aims of the investigation being
      performed.

PMID- 1392686
TI  - A crossroads for British dentistry.

PMID- 1392687
TI  - Incidence of positive aspiration in the Gow-Gates mandibular block.
AB  - Evidence strongly suggests that rigorous precautions should be taken to avoid
      accidental intravascular injection of local anesthetic solutions. In this study,
      3,000 patients each received a Gow-Gates mandibular block, resulting in a
      positive aspiration frequency of 1.6%. In the conventional inferior alveolar
      block technique, a range of positive aspirations from 3.6% to 22% has been noted.
      The Gow-Gates block has other important advantages over the conventional block.
      By observing the landmarks and the depth of penetration, it is possible to
      reinsert the needle with a reasonable assurance of a negative aspiration at the
      second attempt. The conventional technique suffers the major disadvantage that
      needle insertion techniques which produce the highest rates of clinically
      successful pain control run the greatest risk of vascular penetration. Operators
      skilled in the Gow-Gates technique should be able to achieve a positive
      aspiration rate of less than 2%. The technique is unique among oral nerve block
      procedures in that the preferred injection site for maximum efficacy is also the
      site that is least likely to result in vascular penetration.

PMID- 1392688
TI  - Intraoral conduction anesthesia with epinephrine-containing local anesthetics and
      arterial epinephrine plasma concentration.
AB  - Following conduction anesthesia using either lidocaine 2% with epinephrine
      1:80,000, articaine 4% with epinephrine 1:100,000, or articaine 4% with
      epinephrine 1:200,000, the arterial plasma epinephrine concentration was
      measured. Eighteen healthy young patients scheduled for osteotomy of a mandibular
      third molar were studied. Each local anesthetic-epinephrine combination was
      tested in six patients. There was no significant difference in the arterial
      plasma epinephrine concentration after injection of 2 mL of the studied
      anesthetic-epinephrine combinations. The result was explained by the
      concentration difference in the local anesthetics. Although the vasodilating
      action of lidocaine and articaine is almost identical, there will be enhanced
      vasodilation by the doubled concentration in the case of articaine (4%) and the
      local resorption of epinephrine may be facilitated. There were no significant
      changes in the measured cardiovascular parameters.

PMID- 1392689
TI  - Local anesthesia of the head and neck.
AB  - In theory, most ear, nose, and throat surgery involving the soft tissues of the
      head and neck may be performed under local anesthesia. This includes surgery on
      the middle ear, even mastoidectomy; partial or total laryngectomies; surgery on
      the nose and paranasal sinuses; and surgery on the major salivary glands. For
      this purpose, local anesthetics, with or without epinephrine, are administered
      either by infiltration injection or by topical application. The selection of
      either local or general anesthesia for a surgical procedure will depend on many
      important factors, not the least of which is the preference of the patient. This
      paper presents factors to be considered in making this choice, as well as
      surgical indications and contraindications to the use of local anesthesia.

PMID- 1392690
TI  - The management of craniofacial pain in a pain relief unit.
AB  - This paper reports the results of 34 craniofacial pain sufferers who were treated
      at the Dudley Pain Relief Unit over a 1-year period. Most of the patients were
      referred by their general medical practitioners. They were adults representing
      all age groups, with a female-male ratio of 4:1. The average history of pain was
      5.5 years. Neuralgic pain (as distinct from temporomandibular joint dysfunction
      syndrome, migrainous disorders, and pain of iatrogenic origin) was most
      frequently seen. Oral drug therapy, local injection of corticosteroids and
      analgesics, peripheral neurolysis, magnetotherapy, hypnotherapy, and acupuncture
      were the lines of management available. By the end of this study period, pain had
      been relieved or eliminated in 30 of the patients (88%).

PMID- 1392691
TI  - Management of an emergency: to be prepared for the unwanted event.
AB  - Every dental office needs an adequate emergency treatment structure. While
      theoretical and practical pregraduate education in emergency medicine is included
      (in differing degrees) in the curricula of dental schools throughout the world,
      postgraduate training is generally undertaken on a voluntary basis. Repeated
      training in emergency techniques is encouraged for the dentist and dental office
      staff, as the trained and coordinated action of the whole team in the dental
      office is necessary when an emergency occurs. Whenever possible, a recognized
      risk factor should be eliminated or its possible influence minimized prior to
      dental treatment. Patients requiring immediate dental therapy will need
      appropriate monitoring, adequate application of systemically acting drugs, or
      even treatment under standby conditions. Diagnostic equipment as well as
      equipment for monitoring the respiratory and cardiovascular systems should be
      available. Several monitors (blood pressure, ECG, and pulsoximetry) have been
      introduced to dentistry and have their indications in special patient groups.
      Clear therapeutic concepts are the endpoint of proper emergency management. The
      restoration of an undisturbed vital function has to be achieved, followed by
      detailed therapy. Dentists should refresh their knowledge of emergency treatment
      techniques and prepare themselves with therapeutic guidelines.

PMID- 1392692
TI  - Insulin-like growth factor-II increases plasma osteocalcin concentration in
      newborn lambs.
AB  - The influence of GH, IGF-I and IGF-II on plasma 1,25-(OH)2D and osteocalcin (OC)
      concentrations was studied in four groups of five newborn lambs each. They
      received a single i.v. injection of either purified bovine GH (1 IU/mg 600
      micrograms/kg body wt), synthetic human IGF-I (10 or 200 micrograms/kg body wt)
      or synthetic human IGF-II (10 micrograms/kg body wt). Five controls were injected
      the same volume (1 ml) of solvent. IGF-II, but not GH or IGF-I, induced a rapid
      (1.5 h) and sustained (up to 18 h) increase of serum osteocalcin. This effect of
      IGF-II on plasma OC concentration was not mediated by 1,25-(OH)2D, which
      increased in plasma only 18 h after IGF-II injection. These data suggest that IGF
      II stimulates, the in vivo secretion of OC by osteoblasts through a mechanism
      independent of 1,25-(OH)2D. Further studies are necessary to elucidate the
      mechanism of IGF-II action on osteocalcin synthesis and to explain the late
      increase of plasma 1,25-(OH)2D after IGF-II injection.

PMID- 1392693
TI  - Isolation and partial characterization of a growth factor from human cementum.
AB  - Cementum is the mineralized interface through which collagen fibers of
      periodontal connective tissues are anchored onto the tooth surface. We have
      isolated and partially characterized a mitogenic factor from human cementum which
      has properties different from other growth factors. Cementum was harvested from
      healthy human teeth, extracted in 1.0 M CH3COOH and mitogenic activities were
      fractionated by heparin-affinity chromatography. Proteins eluted by 0.4-0.6 M
      NaCl, which contained most of the cementum mitogenic activity, were precipitated
      by trichloroacetic acid and resolved by HPLC through ion-exchange and reverse
      phase columns. NaDodSO4-polyacrylamide gel electrophoresis revealed that the
      purified preparation contained a M(r) 23,000 protein and this protein was
      associated with mitogenic activity. The purified cementum-derived growth factor
      (CGF) was active alone, but at suboptimal concentrations its activity was
      potentiated by small quantities of plasma-derived serum and epidermal growth
      factor (EGF). The activity was resistant to heat, but it was destroyed by trypsin
      digestion. Reduction and alkylation destroyed the mitogenic activity, however
      electrophoretic mobility was not affected. Binding of EGF to fibroblast membranes
      was not affected by the CGF and assays to detect platelet-derived growth factor
      were negative. These characteristics indicated that CGF is a distinct molecular
      species. Our data show that cementum contains several mitogenic factors and that
      CGF is the major cementum mitogen.

PMID- 1392694
TI  - Bone marrow stromal colony formation requires stimulation by haemopoietic cells.
AB  - In mouse bone marrow cultures plated at low cell density, stromal colonies formed
      from colony-forming unit fibroblastic (CFUf) failed to develop unless the
      cultures were supplemented with irradiated feeder cells. Colony-stimulating
      activity was produced by irradiated bone marrow and spleen cells and by
      platelets, was dose dependent, not species specific and was maximal at high serum
      concentration. The efficiency of CFUf colony formation was 1.7 x 10(-4) for
      mechanically disaggregated and 14.6 x 10(-4) for trypsinised bone marrow cells.
      The colonies formed in the presence of feeder cells comprised hundreds of
      fibroblasts. In the absence of feeder cells, small fibroblast foci and single
      fibroblasts only were present in cultures. PDGF, IL-3 and EGF did not substitute
      for the colony-stimulating activity of feeder cells. These results suggest that
      CFUf colony formation requires growth factor(s) released by platelets and
      megakaryocytes which remain to be identified.

PMID- 1392695
TI  - Mechanisms of fibronectin-mediated attachment of osteoblasts to substrates in
      vitro.
AB  - Adhesive proteins of plasma and the extracellular matrix, such as fibronectin,
      adsorbed onto surfaces mediate cell/substrate adhesion. In a series of
      experiments, the roles of the type III connecting segment (IIICS) adhesion sites
      (specifically, CS1 and CS5 peptides) of fibronectin, heparan sulfate
      proteoglycan, endogenous proteins, and passive attachment in fibronectin-mediated
      osteoblast attachment were examined in vitro. The CS1 and CS5 peptides of the
      IIICS of fibronectin had no effect on osteoblast attachment. Blocking the heparin
      binding domains of fibronectin inhibited osteoblast attachment by 40-45%, which
      is complementary to inhibition results previously obtained with the RGDS
      tetrapeptide. Endogenously synthesized and secreted proteins played a role in
      maintaining and repairing the osteoblast surface. Osteoblast attachment to
      fibronectin, but not to the nonadhesive protein albumin, occurred via active
      mechanisms in that the process was dependent on free sulfhydryl groups, divalent
      cations and temperature.

PMID- 1392696
TI  - On the rat model of human osteopenias and osteoporoses.
AB  - The idea that rats cannot model human osteopenias errs. The same mechanisms
      control gains in bone mass (longitudinal bone growth and modeling drifts) and
      losses (BMU-based remodeling), in young and aged rats and humans. Furthermore,
      they respond similarly in rats and man to mechanical influences, hormones, drugs
      and other agents.

PMID- 1392697
TI  - Comparison of a rapid (2-h) versus a slow (24-h) infusion of alendronate in the
      treatment of hypercalcemia of malignancy.
AB  - Alendronate (aminohydroxybutylidene bisphosphonate) is a potent inhibitor of bone
      resorption but the role of the duration of intravenous infusion in its efficacy
      profile is unclear. In a two-centre, parallel, randomized, double-blind study, 20
      patients with tumoral hypercalcemia received a single 10-mg i.v. infusion over
      either 2 h (group A, n = 10) or 24 h (group B, n = 10). Recurrences (n = 6) were
      retreated using the same regimen. Pretreatment plasma calcium (Ca) was 3.32 +/-
      0.08 mM (mean +/- SEM) for all patients. Treatment A and B were associated with
      similar temporal profiles for onset, time to reach normocalcemia, (6 vs 5 days),
      nadir (day 6: 2.45 +/- 0.06 vs 2.43 +/- 0.08 mM) and time to relapse (day 21).
      Normocalcemia (2.15-2.55 mM) was achieved in seven (A) and nine (B) patients with
      other cases being partial responders (Ca: 2.65-2.76 mM). A significant decrease
      of urinary calcium and hydroxyproline excretion and a significant increase of PTH
      accompanied Ca normalization in both groups. Ca response was 50% lower on 2nd
      treatment with alendronate. Both treatments were well tolerated with transient
      mild fever being the most common adverse experience. In conclusion, whether
      infused over 2 or over 24 h, a single dose of 10 mg alendronate led to
      normalization of tumoral hypercalcemia in a large majority of cases.

PMID- 1392699
TI  - The effect of vertebral collapse on spinal bone mineral density measurements in
      osteoporosis.
AB  - Bone mineral density (BMD) of the lumbar spine (L1-L4) was measured using dual
      energy x-ray absorptiometry (DXA) in 57 postmenopausal women with spinal
      osteoporosis aged 50-82 years (average age 64). For each vertebra between L1 and
      L4, the BMD was compared to age-matched normal population values and a Z score
      obtained. Twenty three patients had between one and three collapsed vertebrae
      from L1 to L4. The average Z score for fractured vertebrae was -1.62 but for
      uncollapsed vertebrae was -2.26 (P less than 0.001). The difference in Z scores
      obtained for collapsed and uncollapsed vertebrae was greater where only one
      fracture was present (0.803) compared to two (0.577) or three fractures (0.245).
      The average increase in density for a fractures vertebra was 0.070 g/cm2. For L1
      vertebral fractures alone the average increase in BMD was 0.096 g/cm2, L2
      vertebral fractures 0.041 g/cm2, L3 fractures 0.029 g/cm2 and L4 fractures 0.062
      g/cm2. It is concluded that as vertebral collapse is not alway detected using DXA
      and usually causes a rise in BMD, spinal x-rays are necessary to avoid
      misinterpretation of a falsely elevated BMD in osteoporotic patients,
      particularly in longitudinal studies or when monitoring therapy, where small
      changes in BMD are important.

PMID- 1392698
TI  - Can nandrolone add to the effect of hormonal replacement therapy in
      postmenopausal osteoporosis?
AB  - Thirty-six women with postmenopausal osteoporosis (31 of them with at least one
      non-traumatic vertebral compression fracture) were matched pair-wise as to age,
      years since menopause and body mass index and randomized to receive either
      cyclical estrogen-progestagen replacement treatment (group 1) or the same
      treatment plus nandrolone decanoate (group 2). During the first year of treatment
      in both groups the forearm BMC (SPA) rose proximally and distally 2-3%. Over 2
      years the increments of forearm BMC in both groups were up to 4.5%. Lumbar BMC
      (DPA) rose in both groups nearly 10% over the first year and 12-12.5% over 2
      years. The cancellous bone density of L3 (QCT) showed in 6 months an increase of
      21% in group 1 and 29% in group 2 to subsequently stay at that level. All these
      changes from the basal levels were highly significant but there were no
      significant differences between the two groups. These two conclusions were also
      drawn with regard to the induced fall of serum alkaline phosphatase (-23%),
      osteocalcin (-35% to -44%) and procollagen I (-15% to -22%) and of the fasting
      urinary hydroxyproline (-33% to -36%). No significant increase in the number of
      newly deformed vertebrae occurred in 2 years.

PMID- 1392700
TI  - Selected bibliography.

PMID- 1392701
TI  - Is the child father of the man?

PMID- 1392702
TI  - The supraregional assay service.

PMID- 1392704
TI  - The end of scientific journals?

PMID- 1392703
TI  - Detecting susceptibility to malignant hyperthermia.

PMID- 1392705
TI  - Vertebral fractures.

PMID- 1392706
TI  - Relation of infant feeding to adult serum cholesterol concentration and death
      from ischaemic heart disease.
AB  - OBJECTIVE: To examine whether method of infant feeding is associated with adult
      serum lipid concentrations and mortality from ischaemic heart disease. DESIGN:
      Follow up study of men born during 1911-30. SETTING: Hertfordshire, England.
      SUBJECTS: 5718 men, for 5471 of whom information on infant feeding had been
      recorded by health visitors and 1314 of whom had died. 485 of the men born during
      1920-30 and still living in Hertfordshire who had blood lipid measurements. MAIN
      OUTCOME MEASURES: Death from ischaemic heart disease; serum cholesterol and
      apolipoprotein concentrations. RESULTS: 474 men had died from ischaemic heart
      disease. Standardised mortality ratios were 97 (95% confidence interval 81 to
      115) in men who had been breast fed and had not been weaned at 1 year, 79 (69 to
      90) in breast fed men who had been weaned at 1 year, and 73 (59 to 89) in men who
      had been breast and bottle fed. Compared with men weaned before one year men not
      weaned had higher mean serum concentrations of total cholesterol (6.9 (not
      weaned) v 6.6 (weaned) mmol/l), low density lipoprotein cholesterol (5.0 v 4.6
      mmol/l) and apolipoprotein B (1.14 v 1.08 g/l). Men who had been bottle fed also
      had a high standardised mortality ratio for ischaemic heart disease (95; 68 to
      130) and high mean serum concentrations of total cholesterol (7.0 mmol/l), low
      density lipoprotein cholesterol (5.1 mmol/l), and apolipoprotein B (1.14 g/l). In
      all feeding groups serum apolipoprotein B concentrations were lower in men with
      higher birth weight and weight at 1 year. CONCLUSIONS: Age of weaning and method
      of infant feeding may influence adult serum low density lipoprotein cholesterol
      concentrations and mortality from ischaemic heart disease. Adult serum
      apolipoprotein B concentrations are related to growth in fetal life and infancy.

PMID- 1392707
TI  - Reliability and effectiveness of screening for hearing loss in high risk
      neonates.
AB  - OBJECTIVE: To establish the reliability and effectiveness of screening for
      hearing loss by brainstem auditory evoked potential testing in high risk
      neonates. DESIGN: Seven year investigation of newborn babies admitted to a
      special care baby unit and monitored through a regional children's audiology
      unit. SETTING: Special care baby unit and children's audiology department,
      Belfast. SUBJECTS: 405 neonates admitted to the baby unit, during 1 October 1982
      to 31 March 1987. MAIN OUTCOME MEASURES: Presence of hearing impairment, type and
      severity of hearing impairment, mortality. RESULTS: 85 children failed the
      screening test, 62 of whom were followed up. Five children had severe bilateral
      sensorineural impairment and 12 had conductive impairment requiring surgical
      intervention. A further 18 had severe neurological disorder detected. The
      sensitivity of screening was 100% and specificity was 88%. If the procedure was
      introduced into routine clinical practice the mean age at diagnosis for all
      children with severe perinatal hearing impairment would be 11 (median 1) months.
      The mean age at diagnosis with the health visitor screening service was 23 (19)
      months (difference 10 months, 95% confidence interval 6 to 16 months; p <
      0.0001). CONCLUSION: Screening for hearing loss in high risk neonates is highly
      reliable and cost effective. It also provides valuable neurophysiological
      information. Routine testing of these infants would result in over half of all
      children with severe bilateral perinatal sensorineural hearing impairment being
      identified by 2 months of age. This would make an important contribution to the
      habilitation of this socially, emotionally, and educationally vulnerable group.

PMID- 1392708
TI  - Comparison of female to male and male to female transmission of HIV in 563 stable
      couples. European Study Group on Heterosexual Transmission of HIV.
AB  - OBJECTIVE: To identify risk factors for heterosexual transmission of HIV and to
      compare the efficiency of male to female and female to male transmission. DESIGN:
      Cohort study of heterosexual couples. Regular partners of HIV infected subjects
      were tested and both members of the couples interviewed every six months. HIV
      prevalence in partners was analysed according to the characteristics of the
      couples. SETTING: Nine European countries. SUBJECTS: 563 couples comprising 156
      female index patients with their 159 male partners and 400 male index patients
      with their 404 female partners. Partners reporting risk factors other than sexual
      contacts with the index patient were excluded. MAIN OUTCOME MEASURES: HIV
      infection in partners and high risk sexual behaviour. RESULTS: Overall, 19 (12%)
      male partners and 82 (20%) female partners were infected with HIV, suggesting
      that male to female transmission is 1.9 (95% confidence interval 1.1 to 3.3)
      times more effective than female to male transmission. An advanced stage of HIV
      infection in the index patient (odds ratio 17.6; 4.9 to 62.7) and sexual contacts
      during menses (3.4; 1.0 to 11.1) increased the risk of female to male
      transmission and stage of infection (2.7; 1.5 to 4.9), anal sex (5.1; 2.9 to
      8.9), and age of the female partner (3.9; 1.2 to 13.0 for age > 45 years)
      increased the risk of male to female transmission. None of the 24 partners who
      had used condoms systematically since the first sexual contact was infected.
      CONCLUSIONS: Several factors which potentiate the risk of transmission through
      unprotected vaginal intercourse have been identified. Knowledge of these factors
      could be helpful for counselling patients infected with HIV and their sexual
      partners.

PMID- 1392709
TI  - Is Bordetella pertussis clonal?
AB  - OBJECTIVE: To establish whether Bordetella pertussis is essentially clonal.
      DESIGN: Analysis of restriction fragments of XbaI digests of DNA from clinical
      and control isolates of B pertussis by pulse field gel electrophoresis.
      MATERIALS: 105 isolates of B pertussis: 67 clinical isolates from throughout the
      United Kingdom and 23 from Germany (collected during the previous 18 months);
      vaccine strains 2991 and 3700; and 13 control isolates from Manchester
      University's culture collection. MAIN OUTCOME MEASURES: Frequency of DNA types
      according to country of origin and classical serotyping. RESULTS: 17 DNA types
      were identified on the basis of the variation in 11 fragments, banding at 200-412
      kilobases; 15 types were found in the clinical and control isolates from the
      United Kingdom and seven in those from Germany. There was no correlation with
      serotype. DNA type 1 was the commonest overall (22/105 strains, 22%),
      predominating in serotypes 1,2 and 1,2,3 and including the vaccine strains but
      not the isolates from Germany. CONCLUSIONS: Current infections due to B pertussis
      are not caused by a clonal pathogen as multiple strains are circulating in a
      given population at one time. There is also considerable epidemiological
      variation in the pathogen population between countries. These findings may have
      implications for the design of acellular vaccines.

PMID- 1392710
TI  - Primary and preschool immunisation in Grampian: progress and the 1990 contract.
AB  - OBJECTIVE: To examine changes in immunisation performance in Grampian region
      after the introduction of the 1990 contract for general practitioners. DESIGN:
      Retrospective descriptive study using data held on the Grampian immunisation
      record system's computer. SETTING: All 95 general practices in Grampian region
      (313 general practitioners). PATIENTS: All children in the primary immunisation
      and preschool booster age groups. This formed two groups of children for each of
      the four calendar quarters of 1990 and first three quarters of 1991 analysed as
      (a) those aged 2 years on the first day of the relevant quarter and (b) those
      aged 5 years on the first day of the relevant quarter, with an average population
      of 6600 and 6400 respectively. MAIN OUTCOME MEASURE: Percentage immunised by
      practice. RESULTS: For primary immunisation the number of practices achieving
      immunisation rates of at least 95% increased from 29 (31%) to 76 (81%), and
      practices achieving 90% rates rose from 69 (73%) to 87 (93%). For preschool
      boosters, the number of practices achieving at least 95% immunisation rates
      increased from 22 (23%) to 61 (64%). By the end of September 1991, 76 (80%)
      practices were achieving at least 90% levels compared with 36 (39%) at the
      beginning of 1990. Since the beginning of 1989 the proportion of immunisations
      not given by general practitioners declined from 14% to 2%. CONCLUSIONS: Primary
      and preschool immunisation rates for preschool children in Grampian showed a
      sustained improvement during 1990 and consolidation in 1991. Although overall
      trends were unchanged, 18 months after the introduction of the 1990 contract only
      one practice failed to meet lower target levels of 70% for both primary and
      preschool immunisation. By September 1991 more than three out of four practices
      had reached levels of at least 95% for primary immunisation.

PMID- 1392711
TI  - Trends in hospital admission rates for asthma in children.

PMID- 1392712
TI  - Communication between general practitioners and consultants: what should their
      letters contain?
AB  - OBJECTIVE: To canvass the views of all general practitioners and consultants
      working in Newcastle upon Tyne on the content of referral letters and replies,
      the feasibility of standardising certain aspects of referral letters, and the use
      of communications data for audit purposes. DESIGN: A postal questionnaire was
      sent to all general practitioners and consultants in Newcastle upon Tyne in May
      1991. Questions were asked about the clinical and administrative content of
      letters, the utility of standard categories to state the reason for referral, the
      idea of using letters for feedback purposes, and communications as a potential
      topic for professionally led audit. SETTING: Area served by Newcastle upon Tyne
      Family Health Services Authority and District Health Authority. RESULTS: Replies
      were received from 274 (77%) doctors (115 general practitioners and 159
      consultants). A majority (225; 82%) were in favour of items defined as "always
      important" forming a minimum requirement for referral letters and for
      consultants' replies. Using standardised categories to state the reason for
      referral was not endorsed: 102 (89%) general practitioners and 132 (83%)
      consultants preferred referrers to use their own words. Using referral
      communications to provide feedback was less popular with consultants (54; 34%)
      than general practitioners (72; 63%). Finally, a majority of doctors (179; 65%)
      were in favour of using written communications as a topic for professionally led
      audit. CONCLUSIONS: A high degree of consensus exists among clinicians about the
      content of referral communications. Although doctors may still reject the concept
      of standardised communications, they have unambiguously endorsed a standard for
      communication that they can aspire to, and they are prepared to use it as a
      yardstick for their actual performance.

PMID- 1392713
TI  - Primary medical care in former East Germany: the frosty winds of change.

PMID- 1392714
TI  - Counselling HIV positive haemophilic men who wish to have children.

PMID- 1392715
TI  - Missed neuroleptic malignant syndrome.

PMID- 1392716
TI  - Manpower.

PMID- 1392717
TI  - Adoption in utero.

PMID- 1392718
TI  - Changing disease patterns in AIDS.

PMID- 1392720
TI  - Accreditation after Goldstein.

PMID- 1392719
TI  - Ocular injuries from boxing.

PMID- 1392721
TI  - Accreditation after Goldstein.

PMID- 1392722
TI  - Accreditation is linked to other issues.

PMID- 1392723
TI  - Renal protective effect of enalapril in diabetic nephropathy.

PMID- 1392724
TI  - Morbidity due to asthma.

PMID- 1392725
TI  - Rehabilitation of amputees.

PMID- 1392726
TI  - Rehabilitation of amputees.

PMID- 1392727
TI  - Occupational causes of disorders in the upper limbs.

PMID- 1392728
TI  - Neonatal mortality in Germany since the Chernobyl explosion.

PMID- 1392729
TI  - Open access mammography.

PMID- 1392730
TI  - Patients with secondary polycythaemia as blood donors.

PMID- 1392731
TI  - Corticosteroids and male infertility with an immunological basis.

PMID- 1392732
TI  - Goya's living skeleton.

PMID- 1392733
TI  - Restricted entry to the tamoxifen trial.

PMID- 1392734
TI  - The Bevan factor.

PMID- 1392735
TI  - Acute medical beds could be cut.

PMID- 1392736
TI  - Contraception for the under 16s.

PMID- 1392737
TI  - Prison medicine.

PMID- 1392738
TI  - Randomised clinical trials in general practice.

PMID- 1392739
TI  - Health policy in Europe.

PMID- 1392740
TI  - Avoiding amputation.

PMID- 1392741
TI  - Asthma's changing prevalence.

PMID- 1392742
TI  - Adjuvant treatment for breast cancer: the overview.

PMID- 1392743
TI  - Japan bans pill through fear of HIV.

PMID- 1392744
TI  - Home HIV tests banned in Britain.

PMID- 1392745
TI  - Fetal nuchal translucency: ultrasound screening for chromosomal defects in first
      trimester of pregnancy.
AB  - OBJECTIVE: To examine the significance of fetal nuchal translucency at 10-14
      weeks' gestation in the prediction of abnormal fetal karyotype. DESIGN:
      Prospective screening study. SETTING: The Harris Birthright Research Centre for
      Fetal Medicine, King's College Hospital, London. SUBJECTS: 827 fetuses undergoing
      first trimester karyotyping by amniocentesis or chorionic villus sampling. MAIN
      OUTCOME MEASURE: Incidence of chromosomal defects. RESULTS: The incidence of
      chromosomal defects was 3% (28 of 827 cases). In the 51 (6%) fetuses with nuchal
      translucency 3-8 mm thick the incidence of chromosomal defects was 35% (18
      cases). In contrast, only 10 of the remaining 776 (1%) fetuses were chromosomally
      abnormal. CONCLUSION: Fetal nuchal translucency > or = 3 mm is a useful first
      trimester marker for fetal chromosomal abnormalities.

PMID- 1392746
TI  - Respiratory symptoms and atopy in Aberdeen schoolchildren: evidence from two
      surveys 25 years apart.
AB  - OBJECTIVE: To estimate changes in the prevalence of respiratory symptoms and the
      reported diagnoses of asthma, eczema, and hay fever in primary school children in
      Aberdeen between 1964 and 1989. DESIGN: Determination of incidence prevalence and
      prevalence from survey data. SETTING: Aberdeen, Scotland. PARTICIPANTS: 2743
      primary school children (aged 8-13) from 1964 and 4003 [corrected] from 1989.
      MAIN OUTCOME MEASURES: Survey data on whether, according to the parent or
      guardian, the child wheezed or was troubled with shortness of breath; the number
      of episodes of breathlessness in the past year; and whether asthma, eczema, or
      hay fever had ever been diagnosed. RESULTS: Questionnaires were completed by the
      parents of 2510 children in 1964 and 3403 children in 1989. The prevalence of
      wheeze rose from 10.4% in 1964 to 19.8% in 1989, and the prevalence of episodes
      of shortness of breath increased from 5.4% to 10.0%. In both surveys wheeze and
      shortness of breath were more prevalent in boys than in girls. The reported
      diagnosis of asthma rose from 4.1% to 10.2%, hay fever from 3.2% to 11.9%, and
      eczema from 5.3% to 12%. The proportion of boys suffering from eczema rose from
      47.7% to 60.0%. Hay fever showed a similar increase, from 49.4% to 60.1%, in boys
      over the 25 year period. Though the parents of a higher proportion of children
      with wheeze were aware of the diagnosis of asthma in 1989, because of the
      increased prevalence of wheeze the absolute number of parents of wheezy children
      who were not aware of a diagnosis of asthma increased from 7.4% to 9.6% of the
      population studied. CONCLUSION: The higher diagnosis rate for asthma is due not
      simply to changes in diagnostic fashion but reflects an increase over the past 25
      years in the prevalence of respiratory symptoms, which in turn may reflect a more
      general change in the prevalence of atopy, the increase in which was particularly
      noticeable in boys. This increase explains some of the increase in hospital
      admission rates for children with asthma.

PMID- 1392747
TI  - A survey of hospital toilet facilities.
AB  - OBJECTIVE: To assess the quality of toilet facilities available for disabled
      people in a large provincial teaching hospital. DESIGN: Survey of toilet
      facilities for patients on the wards and in the outpatient department. SETTING:
      Teaching hospital in Leeds. RESULTS: Although the quality of toilet facilities
      varied, none met the standards recommended by the British Standards Institution.
      The worst facilities were found on a ward accommodating elderly patients, where
      the toilets were unsuitable for use by disabled people and bedside commodes had
      to be used instead. CONCLUSION: Toilet provision within a major hospital failed
      to meet standards required for disabled people. Admission to hospital may
      therefore result in loss of independence and dignity. If hospitals are to be
      centres of excellence, greater consideration must be given to the requirements of
      disabled people in the design of new wards, and current inadequate facilities
      should be upgraded.

PMID- 1392748
TI  - Perforation of gloves in an accident and emergency department.

PMID- 1392749
TI  - Sex bias in the BMJ: an audit.

PMID- 1392750
TI  - Hospital admission and the start of benzodiazepine use.

PMID- 1392752
TI  - Parotitis due to nicardipine.

PMID- 1392751
TI  - Acute hypothermia due to penicillin.

PMID- 1392753
TI  - Thrombotic thrombocytopenic purpura due to rifampicin.

PMID- 1392755
TI  - Can health visitors prevent fractures in elderly people?
AB  - OBJECTIVES: To assess whether intervention by a health visitor could reduce the
      number of fractures, over a four year period, in those aged 70 and over. DESIGN:
      Randomised, controlled trial; randomisation by household. SETTING: General
      practice in a market town. SUBJECTS: Of 863 patients aged 70 and over on the
      practice records, 674 were traced and successfully interviewed; 350 were assigned
      to the intervention group, 324 as controls. INTERVENTION: The people in the
      intervention group were allocated to the care of a health visitor. The approach
      was four pronged: assessment and correction of nutritional deficiencies,
      including reducing smoking and alcohol intake; assessment and referral of medical
      conditions such as heart block or inappropriate medication; assessment and
      correction of environmental hazards in the home such as poor lighting; assessment
      and improvement of fitness--for example, exercise classes for the moderately fit.
      The intervention continued for four years. MAIN OUTCOME MEASURE: Fracture rate
      over four years. RESULTS: The incidence of fractures was 5% (16/350) in the
      intervention group and 4% (14/324) in the control group (difference not
      significant). CONCLUSIONS: A health visitor visiting a group of people aged 70
      and over and using simple preventive measures had no effect on the incidence of
      fractures.

PMID- 1392754
TI  - Edinburgh primary care depression study: treatment outcome, patient satisfaction,
      and cost after 16 weeks.
AB  - OBJECTIVE: To compare the clinical efficacy, patient satisfaction, and cost of
      three specialist treatments for depressive illness with routine care by general
      practitioners in primary care. DESIGN: Prospective, randomised allocation to
      amitriptyline prescribed by a psychiatrist, cognitive behaviour therapy from a
      clinical psychologist, counselling and case work by a social worker, or routine
      care by a general practitioner. SUBJECTS AND SETTING: 121 patients aged between
      18 and 65 years suffering depressive illness (without psychotic features) meeting
      the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third
      Edition for major depressive episode in 14 primary care practices in southern
      Edinburgh. MAIN OUTCOME MEASURES: Standard observer rating of depression at
      outset and after four and 16 weeks. Numbers of patients recovered at four and 16
      weeks. Total length and cost of therapist contact. Structured evaluation of
      treatment by patients at 16 weeks. RESULTS: Marked improvement in depressive
      symptoms occurred in all treatment groups over 16 weeks. Any clinical advantages
      of specialist treatments over routine general practitioner care were small, but
      specialist treatment involved at least four times as much therapist contact and
      cost at least twice as much as routine general practitioner care. Psychological
      treatments, especially social work counselling, were most positively evaluated by
      patients. CONCLUSIONS: The additional costs associated with specialist treatments
      of new episodes of mild to moderate depressive illness presenting in primary care
      were not commensurate with their clinical superiority over routine general
      practitioner care. A proper cost-benefit analysis requires information about the
      ability of specialist treatment to prevent future episodes of depression.

PMID- 1392756
TI  - Law, coercion, and the public health.

PMID- 1392757
TI  - Public opinion, the NHS, and the media: changing patterns and perspectives.

PMID- 1392758
TI  - Health policies in the general election.

PMID- 1392760
TI  - European research: back to pre-eminence?

PMID- 1392759
TI  - Critical ischaemia of the lower limb: femorodistal bypass in preference to
      amputation.

PMID- 1392761
TI  - ABC of colorectal diseases. Anal fissures and fistulas.

PMID- 1392762
TI  - The new NHS: first year's experience. Freeman Hospital: working to improve
      services.

PMID- 1392763
TI  - Injuries sustained on "bouncy castles".

PMID- 1392764
TI  - Self poisoning by adolescents.

PMID- 1392765
TI  - The cholesterol controversy.

PMID- 1392767
TI  - The cholesterol controversy.

PMID- 1392766
TI  - The cholesterol controversy.

PMID- 1392768
TI  - The cholesterol controversy.

PMID- 1392769
TI  - Age associated memory impairment.

PMID- 1392770
TI  - Medical abortion.

PMID- 1392771
TI  - Medical abortion.

PMID- 1392772
TI  - Functional iron deficiency during erythropoietin treatment.

PMID- 1392773
TI  - Back pain and thrombolysis.

PMID- 1392774
TI  - Monitoring lithium treatment.

PMID- 1392775
TI  - Monitoring lithium treatment.

PMID- 1392776
TI  - Measles, mumps, and rubella vaccine: time for a two stage policy.

PMID- 1392777
TI  - Morphine for pain in infants.

PMID- 1392778
TI  - Organ donation from intensive care units.

PMID- 1392779
TI  - Missing women.

PMID- 1392780
TI  - Outcome measures should be relevant.

PMID- 1392781
TI  - Cold comfort for carers.

PMID- 1392782
TI  - Home grown heterosexually acquired HIV infection.

PMID- 1392783
TI  - Diagnosing pulmonary embolism.

PMID- 1392784
TI  - Harm minimisation for drug misusers.

PMID- 1392785
TI  - NCEPOD: revisiting perioperative mortality.

PMID- 1392786
TI  - The role of local research ethics committees.

PMID- 1392787
TI  - Reversing vasectomy.

PMID- 1392788
TI  - AIDS conference shifts focus.

PMID- 1392789
TI  - India gets money to fight AIDS.

PMID- 1392790
TI  - Risk of second primary cancers after Hodgkin's disease by type of treatment:
      analysis of 2846 patients in the British National Lymphoma Investigation.
AB  - OBJECTIVE: To analyse the risk of second primary cancers during long term follow
      up of patients with Hodgkin's disease. DESIGN: Cohort study. SETTING: The British
      National Lymphoma Investigation (a collaborative group of over 60 participating
      centres in Britain treating lymphomas). PATIENTS: 2846 patients first treated for
      Hodgkin's disease during 1970-87, for whom follow up was complete in 99.8%. MAIN
      OUTCOME MEASURES: Second primary cancers; uniform pathology reviews confirmed the
      diagnosis of Hodgkin's disease and of second primary non-Hodgkin's lymphomas.
      RESULTS: 113 second primary cancers occurred. Relative risk of cancer other than
      Hodgkin's disease was 2.7 (95% confidence interval 2.3 to 3.3) compared with the
      general population, with significant risk of leukaemia (16.0(9.1 to 26.0)); non
      Hodgkin's lymphoma (16.8(9.8 to 26.9)); and cancers of the colon (3.2 (1.4 to
      6.2)), lung (3.8 (2.6 to 5.4)), bone (15.1 (1.8 to 54.7)), and thyroid (9.4 (1.1
      to 33.9)). Absolute excess risk associated with treatment was greater for solid
      tumours than for leukaemia and lymphomas. Relative risk of leukaemia increased
      soon after treatment, reaching a peak after five to nine years. It was increased
      substantially after chemotherapy (27.9 (12.7 to 52.9)), combined treatment with
      radiotherapy and chemotherapy (21.5 (7.9 to 46.8)), and relative to number of
      courses of chemotherapy but was not significantly increased after radiotherapy
      (2.5 (0.1 to 14.1)). Relative risk of non-Hodgkin's lymphoma increased in the
      first five years after treatment and remained high but showed no clear relation
      with type or extent of treatment. Relative risk of solid tumours was less raised
      initially but increased throughout follow up and for lung cancer 10 years or more
      after entry was 8.3 (4.0 to 15.3). The risk of solid tumours increased after
      treatments including radiotherapy and after chemotherapy alone. The risk after
      chemotherapy increased significantly with time since first treatment. CONCLUSION:
      The risk of solid cancer, not of leukaemia, is the major long term hazard of
      treatment for Hodgkin's disease, and this seemed to apply after chemotherapy as
      well as after radiotherapy. These risks of second cancers are important in choice
      of treatment and in follow up of patients, but they are small compared with the
      great improvements in survival which have been brought about by modern
      therapeutic methods for Hodgkin's disease.

PMID- 1392792
TI  - Predicting psychiatric admission rates.
AB  - OBJECTIVE: To determine the numbers of actual and expected psychiatric admissions
      for the residents of the district health authorities of England and to develop a
      model to indicate which social, health status, and service provision factors best
      explain the variation of the actual from the expected psychiatric admissions; to
      use this model to predict psychiatric admission for district health authorities
      as an aid to resource allocation. DESIGN: The actual psychiatric admission for
      district health authority residents were extracted from data of the 1986 Mental
      Health Enquiry. Expected admissions were calculated using the age, sex, and
      marital status structure of each district health authority and the national
      psychiatric admission rates related to age, sex, and marital status. Standardised
      psychiatric admission ratios were calculated as the ratios of the numbers of
      actual to expected psychiatric admissions. A wide range of social, health status,
      and service provision data were used as the explanatory variables in regression
      analyses to determine which combination of factors best explained the variation
      between districts of standardised psychiatric admission ratios. SETTING: The
      168,652 psychiatric admissions recorded for the 1986 Mental Health Enquiry, after
      exclusion of mental handicap and psychogeriatric admissions. RESULTS: The actual
      number of psychiatric admissions varied from 79% above to 54% below the expected
      number of admissions from age, sex, and marital status for the districts of
      England. The most powerful variables to explain this variation were the rate of
      notification of drug misusers, standardised mortality ratios, and levels of
      illegitimacy in each district. A complex model was developed which could be used
      to predict district psychiatric admissions as an aid to resource allocation. A
      simpler model was also developed (which was less powerful than the more complex
      model) based on the underprivileged area score. One advantage of this model was
      that it could be used at the level of electoral wards as well as district health
      authorities.

PMID- 1392791
TI  - Drowning and near drowning in children in the United Kingdom: lessons for
      prevention.
AB  - OBJECTIVES: To determine the pattern of drowning and near drowning of children in
      Britain and identify means of prevention. DESIGN: Study of drowned and nearly
      drowned children under 15 years old. SETTING: United Kingdom, 1988 and 1989.
      SUBJECTS: Children under 15 years either drowning or admitted to hospital after a
      submersion incident. MAIN OUTCOME MEASURES: Number of nearly drowned children,
      obtained from consultant paediatricians returning monthly notification cards
      through the British Paediatric Surveillance Unit. Number of drowned children
      notified by the Office of Population Censuses and Surveys and other national
      epidemiological offices; information from coroners. RESULTS: 306 children had
      confirmed submersion incidents: 149 died and 157 survived after near drowning.
      The annual incidence in England and Wales was 1.5/100,000, and mortality
      0.7/100,000. Mortality was lowest in public pools 6% (2/32) and highest in
      rivers, canals, and lakes (78%, 56/73). Most of the children (263, 83%) were
      unsupervised at the time of the accident. 208 (68%) children were under 5 years
      old. CONCLUSIONS: Drowning and near drowning of children are problems in the
      British Isles. Appropriate supervision and safety barriers seem important for
      preventing such accidents. Improving information on dangers of drowning given to
      parents through the child surveillance programmes, encouraging fencing or
      draining of garden ponds and domestic swimming pools, and increasing supervision
      of swimming in lakes, rivers, and beaches should reduce the number of accidents.

PMID- 1392793
TI  - Short term treatment of dermatophyte onychomycosis with terbinafine.
AB  - OBJECTIVE: To evaluate the effect of short term treatment with terbinafine on
      dermatophytosis. DESIGN: Multicentre, randomised, double blind placebo controlled
      trial of 250 mg/day terbinafine for 12 weeks in dermatophyte onychomycosis.
      SETTING: Eight dermatology centres in the United Kingdom. PATIENTS: 112 patients
      (mean age 44, range 19-78), 99 with mycologically proved toenail infections and
      13 with fingernail infections, of whom eight were subsequently excluded and 19
      failed to complete the study. INTERVENTION: Terbinafine 250 mg daily or placebo
      for 12 weeks. Follow up for 36 weeks after stopping treatment. MAIN OUTCOME
      MEASURES: Mycological cure (negative results on microscopy and culture) and
      clinical cure at the end of follow up, adverse events, and biochemical and
      haematological variables at monthly intervals during treatment. RESULTS: After
      follow up 82% (37/45) (95% confidence interval 68% to 92%) mycological cure and
      69% clinical cure were recorded for evaluable patients treated with terbinafine
      for toenail infection and 71% (5/7) (30% to 96%) mycological cure and clinical
      cure for those treated for fingernail infection. The corresponding values for
      those treated with placebo were 12% (3% to 31%) mycological cure and no clinical
      cure for toenail infections and 33% (1% to 91%) mycological cure and no clinical
      cure for fingernail infections. On an intention to treat basis for toenail
      infections the figures were 73% (38/52) (58% to 85%) mycological cure for
      terbinafine compared with 6% (0% to 30%) for placebo (p less than 0.007). Two
      withdrawals were related to adverse events with terbinafine, and there were no
      significant abnormal laboratory test results. CONCLUSION: 12 weeks' terbinafine
      is effective and safe treatment for nail dermatophytosis.

PMID- 1392794
TI  - Delayed diagnosis in non-insulin dependent diabetes mellitus.

PMID- 1392795
TI  - Inhaled atrial natriuretic peptide and asthmatic airways.

PMID- 1392796
TI  - Hyperinsulinaemia and blood pressure in patients with insulinoma.

PMID- 1392797
TI  - Current uses of ophthalmic lasers.
AB  - Current laser treatments are quick, relatively painless, and well tolerated. Some
      ophthalmic techniques can be performed only by laser while others have a lower
      morbidity than alternative treatments. Peripheral retinal photocoagulation and
      focal photocoagulation now offer greatly improved visual prognosis for diabetic
      patients with proliferative diabetic retinopathy or diabetic macular disease.
      Selected cases of macular degeneration may be treated by focal laser
      photocoagulation. The role of lasers in treating sub-retinal neovascular
      membranes is limited by the extent and location of the membrane at presentation
      and the high risk of recurrence after treatment. Patients with distorted vision
      must be referred urgently for specialist ophthalmic assessment. Flat retinal
      holes and tears may be sealed by laser therapy, thus preventing retinal
      detachment. Short pulsed neodymium-YAG photodisruptive capsulotomy effectively
      clears the visual axis of thickened posterior lens capsule after cataract
      surgery. Short pulsed neodymium-YAG photodisruptive iridotomy may be used to
      treat and prevent angle closure glaucoma. Laser trabeculoplasty aids the control
      of open angle glaucoma. Research is continuing into the role of other lasers in
      managing open angle glaucoma and of photoablative lasers in treating refractive
      errors and superficial corneal disorders.

PMID- 1392798
TI  - Fulminant hepatitis B in infants born to anti-HBe hepatitis B carrier mothers.

PMID- 1392799
TI  - Cholera.

PMID- 1392800
TI  - Day case surgery and workload.

PMID- 1392801
TI  - Postoperative pain control in children.

PMID- 1392802
TI  - Deaths from haemolytic disease of the newborn.

PMID- 1392803
TI  - Treatment of back and neck complaints.

PMID- 1392804
TI  - Ozone depletion and skin cancer.

PMID- 1392805
TI  - Facilitating prevention in primary care.

PMID- 1392806
TI  - Care of asthma in general practice.

PMID- 1392807
TI  - High dose triazolam and anterograde amnesia.

PMID- 1392808
TI  - Site for immunising infants.

PMID- 1392809
TI  - Is Bordetella pertussis clonal?

PMID- 1392810
TI  - Physiotherapy intervention late after stroke.

PMID- 1392811
TI  - Hospital admission and start of benzodiazepine use.

PMID- 1392812
TI  - Side of origin of ovarian cancer.

PMID- 1392813
TI  - Public opinion and purchasing.

PMID- 1392814
TI  - Communication between GPs and consultants.

PMID- 1392815
TI  - Cerebral oedema in diabetic ketoacidosis.

PMID- 1392817
TI  - Refugee health.

PMID- 1392816
TI  - Assisted conception on the NHS?

PMID- 1392818
TI  - Controlling leprosy.

PMID- 1392819
TI  - New developments in the fragile X syndrome.

PMID- 1392820
TI  - AIDS epidemic grows but response slows.

PMID- 1392821
TI  - Reprieve for Thailand's AIDS campaign.

PMID- 1392822
TI  - Erythrocyte sodium-lithium countertransport and blood pressure in identical twin
      pairs discordant for insulin dependent diabetes.
AB  - OBJECTIVE: To investigate whether insulin dependent diabetes is responsible for
      the abnormal behaviour of the carrier in sodium-lithium countertransport and
      whether the diabetic state is associated with rise in blood pressure. DESIGN:
      Case-control study. SETTING: London teaching hospital. SUBJECTS: 44 twin pairs
      discordant for insulin dependent diabetes living in United Kingdom and 44 healthy
      control subjects matched for age, sex, and body mass index. None of the twin
      pairs or the controls had evidence of microalbuminuria. MAIN OUTCOME MEASURES:
      Sodium-lithium countertransport activity in erythrocytes and arterial blood
      pressure. RESULTS: The mean (95% confidence interval) sodium-lithium
      countertransport activity (mmol Li per litre of red blood cells per h) of the
      diabetic twins (0.291 (0.244 to 0.338)) was similar to that of their non-diabetic
      cotwins (0.247 (0.204 to 0.290)); both values were significantly higher than that
      of the controls (0.187 (0.157 to 0.216); p < 0.05). In addition, systolic blood
      pressure was higher in those twins with diabetes (127 (122 to 133) mm Hg) than in
      the non-diabetic cotwins (122 (117 to 127) mm Hg; p < 0.01). There were no
      significant differences in mean diastolic blood pressure between any of the
      groups studied. CONCLUSIONS: The raised erythrocyte sodium-lithium
      countertransport activity in the diabetic twins compared with the controls seems
      to be inherited rather than a consequence of overt diabetes. The higher systolic
      blood pressure in diabetic twins than non-diabetic cotwins indicates that insulin
      dependent diabetes does exert a small influence on systolic blood pressure.

PMID- 1392823
TI  - Impact of HIV infection on mortality in young men in a London health authority.
AB  - OBJECTIVE: To determine the number of deaths attributable to HIV infection among
      men aged 15-64 in a geographically defined population in the United Kingdom.
      DESIGN: Retrospective review of death certificates and linkage with local and
      national HIV and AIDS surveillance data. SETTING: Riverside District Health
      Authority, London. MAIN OUTCOME MEASURES: Numbers of deaths attributed to HIV
      infection in male residents of Riverside aged 15-64 and 15-44 over a six month
      period. Proportion of attributed deaths were (i) identified from death
      certificates by the Office of Population Censuses and Surveys as being due to HIV
      infection and (ii) reported as cases of AIDS or HIV related deaths to the Public
      Health Laboratory Service Communicable Disease Surveillance Centre. RESULTS: 34
      of 213 (16%) deaths in men aged 15-64 and 27 of 69 (39%) deaths in men aged 15-44
      were attributed to HIV infection. Six of 33 (18%) attributed deaths were
      identified by the Office of Population Censuses and Surveys and 32/34 (94%) were
      reported to the Communicable Disease Surveillance Centre. CONCLUSIONS: HIV
      infection was the leading cause of death in male residents of Riverside aged 15
      44 and the third commonest cause of death in those aged 15-64. Most individuals
      dying of known HIV infection were reported to the Communicable Disease
      Surveillance Centre but identification of the true cause of death from the
      process of death certification was poor. Measures to improve the certification of
      HIV and AIDS or the use of AIDS surveillance information correctly to code the
      cause of death needs to be considered to ensure that the true impact of HIV
      infection is reflected in routine mortality statistics.

PMID- 1392824
TI  - Evidence of transmission of tuberculosis by DNA fingerprinting.
AB  - OBJECTIVE: To determine whether a subject who had died of tuberculous meningitis
      had been infected by a neighbour. DESIGN: Retrospective comparison of isolates of
      Mycobacterium tuberculosis from the two cases and from 10 controls by DNA
      fingerprinting. SETTING: Public Health Service Reference Laboratory for
      Mycobacteria and bacterial molecular genetics unit of the London School of
      Hygiene and Tropical Medicine. SUBJECTS: Deceased and neighbour; 10 controls from
      the same city, from whom isolates had been collected over three months before the
      subject's death. MAIN OUTCOME MEASURES: Identity and similarity values (SAB)
      between fingerprint patterns from different isolates obtained by hybridisation of
      restriction fragments produced by PvuII with a probe from the insertion element
      IS6110/986, present in multiple copies throughout the genome of M tuberculosis.
      RESULTS: Isolates from the two cases under investigation had identical
      fingerprints whereas those from the controls were all distinct. Two clusters of
      isolates with a similarity coefficient > 0.25 were identified: in one, four out
      of five patients were born in the midlands (the birth place of the fifth was not
      known) and in the other all three patients were born in the Indian subcontinent.
      CONCLUSIONS: The data are consistent with, but do not prove, transmission of
      tuberculosis from the neighbour to the deceased. Geographical separation of the
      pools of infection may have led to the evolution of distinct clusters of
      fingerprint patterns. DNA fingerprinting of M tuberculosis is a powerful new tool
      for study of the epidemiology and pathogenesis of tuberculosis.

PMID- 1392825
TI  - Tobacco advertising on post offices.

PMID- 1392826
TI  - Treatment of amiodarone induced thyrotoxicosis with carbimazole alone and
      continuation of amiodarone.

PMID- 1392827
TI  - Long term effects of tamoxifen on blood lipid values in breast cancer.

PMID- 1392828
TI  - Midwifery and body fluid contamination.

PMID- 1392829
TI  - Choosing the preventive workload in general practice: practical application of
      the Coronary Prevention Group guidelines and Dundee coronary risk-disk.
AB  - OBJECTIVE: To determine the workload implications for general practice of the
      Coronary Prevention Group and British Heart Foundation action plan for preventing
      heart disease. DESIGN: Computer simulation of plan, including calculation of
      Dundee risk scores, with data from OXCHECK trial. SUBJECTS: 4759 patients aged 35
      64 who had health checks during 1989-91. MAIN OUTCOME MEASURE: Effect of using
      different risk scores as thresholds on workload and coverage of patients at known
      risk. Thresholds of 6-20 were used for cholesterol screening (nearset) and 4-16
      for special care (preset). RESULTS: On the basis of workload a nearset of 8 and
      preset of 12 would be reasonable. This implies cholesterol measurement in 1794
      (37.7%) patients and special care in 1074 (22.6%). However, many patients with
      single risk factors were not allocated to special care at these thresholds: 11
      (37.9%) patients with cholesterol concentrations > or = 10 mmol/l, 21 (33.9%)
      with systolic pressure > or = 180 mm Hg, and 213 (40.7%) heavy smokers (> 20
      cigarettes/day) were missed. The distribution of scores was similar in those at
      established clinical risk, those with family history of heart disease, and
      others. CONCLUSION: The guidelines may help to make best use of resources within
      specific age-sex groups but sound protocols for unifactorial risk assessment and
      modification remain essential.

PMID- 1392830
TI  - Value of the Dundee coronary risk-disk: a defence.

PMID- 1392831
TI  - The primary health care team: history and contractual farces.

PMID- 1392832
TI  - When to stop a clinical trial.

PMID- 1392834
TI  - ABC of colorectal diseases. Rectal prolapse and associated conditions.

PMID- 1392833
TI  - Ocular complications observed in leprosy patients in Romania.

PMID- 1392835
TI  - London's health care.

PMID- 1392836
TI  - London's health care.

PMID- 1392837
TI  - Mixed sex wards.

PMID- 1392838
TI  - Reporting to NCEPOD.

PMID- 1392839
TI  - Reporting to NCEPOD.

PMID- 1392840
TI  - Reporting to NCEPOD.

PMID- 1392841
TI  - Misuse of temazepam.

PMID- 1392842
TI  - Misuse of temazepam.

PMID- 1392843
TI  - Second brain tumour after treatment for pituitary adenoma.

PMID- 1392844
TI  - Growth hormone and recurrence of tumour.

PMID- 1392845
TI  - Videotaped interviews with children suspected of being sexually abused.

PMID- 1392846
TI  - Helping Russia.

PMID- 1392847
TI  - British-Polish workshops on substance misuse services.

PMID- 1392848
TI  - Postmarketing surveillance studies.

PMID- 1392849
TI  - Postmarketing surveillance studies.

PMID- 1392850
TI  - AIDS and ethics in Birmingham: a betrayal of trust.

PMID- 1392851
TI  - A tale of one city.

PMID- 1392852
TI  - Poor Britain.

PMID- 1392853
TI  - Foodborne botulism.

PMID- 1392854
TI  - Screening, ethics, and the law.

PMID- 1392855
TI  - Americans retreat on SI units.

PMID- 1392856
TI  - AIDS without HIV.

PMID- 1392857
TI  - Bone density parathyroid hormone and 25-hydroxyvitamin D concentrations in middle
      aged women.
AB  - OBJECTIVE: To examine the relation between bone density and indices of calcium
      metabolism including parathyroid hormone and 25-hydroxyvitamin D concentrations
      in middle aged women. DESIGN: A cross sectional study. SETTING AND SUBJECTS: 138
      women volunteers aged 45-65 with no known osteoporosis and unselected for disease
      status recruited for a dietary assessment study from the community using general
      practice registers. Volunteer rate was 20%. MAIN OUTCOME MEASURE: Bone mineral
      density measured with dual energy x ray absorptiometry. RESULTS: Bone density at
      the lumbar spine and neck and trochanteric regions of the femur was inversely
      related to serum intact parathyroid hormone concentrations and positively related
      to serum 25-hydroxyvitamin D concentrations. These associations were independent
      of possible confounding factors, including age, body mass index, cigarette
      smoking habit, menopausal status, and use of diuretics and postmenopausal hormone
      replacement therapy. These associations were apparent throughout the whole
      distribution of bone density and 25-hydroxyvitamin D and parathyroid hormone
      concentrations within the normal range, suggesting a physiological relation.
      CONCLUSIONS: The findings are consistent with the hypothesis that parathyroid
      hormone and 25-hydroxyvitamin D concentrations influence bone density in middle
      aged women. Findings from this study together with other work suggest that the
      role of vitamin D in osteoporosis should not be neglected. The associations with
      parathyroid hormone also indicate plausible biological mechanisms. The roughly 5
      10% difference in bone density between top and bottom tertiles of serum 25
      hydroxyvitamin D concentrations, though not large in magnitude, may have
      considerable public health implications in terms of prevention of osteoporosis
      and its sequelae, fractures.

PMID- 1392858
TI  - Low serum cholesterol concentration and short term mortality from injuries in men
      and women.
AB  - OBJECTIVE: To determine whether total serum cholesterol concentration predicts
      mortality from injuries including suicide. DESIGN: Cohort study of men and women
      who had their serum cholesterol concentration measured as part of a general
      health survey in Varmland, Sweden in 1964 or 1965 and were followed up for an
      average of 20.5 years. SUBJECTS: Adults participating in health screening in 1964
      5 (26,693 men and 27,692 women). The study sample was restricted to subjects aged
      45-74 years during any of the 20.5 years of follow-up. MAIN OUTCOME MEASURES:
      Serum cholesterol concentration. Deaths from all injuries and suicides during
      three periods of follow up (0-6 years, 7-13 years, and 14-21 years) according to
      the Swedish mortality register in subjects aged 45-74. Adjustment was made for
      prevalent cancer (identified from the Swedish cancer register) at the time of a
      suicide. RESULTS: A strong negative relation between cholesterol concentration
      and mortality from injuries was found in men during the first seven years of
      follow up. The relative risk in the lowest 25% of the cholesterol distribution
      was 2.8 (95% confidence interval 1.52 to 4.96) compared with the top 25%. Most of
      the excess risk was caused by suicide with a corresponding relative risk of 4.2
      (p for trend = 0.001). Correction for prevalent cancer did not change the
      results. Events occurring during the latter two thirds of the 20.5 years of
      follow up were not predicted. In women no relation between cholesterol
      concentration and mortality from injuries was found. CONCLUSIONS: Together with
      observations from intervention trials the findings support the existence of a
      relation between serum cholesterol concentration and suicide. The causality of
      such a relation is, however, not resolved.

PMID- 1392859
TI  - Central serotonin receptors and delayed gastric emptying in non-ulcer dyspepsia.
AB  - OBJECTIVE: To determine whether central serotonin receptors are involved in the
      pathophysiology of non-ulcer dyspepsia. DESIGN: Between subjects study of solid
      phase gastric emptying and prolactin response to buspirone challenge. SUBJECTS:
      12 patients fulfilling criteria for non-ulcer dyspepsia and 12 age and sex
      matched controls. MAIN OUTCOME MEASURES: Solid phase gastric emptying measured by
      scintigraphic assessment of the movement of a standard meal labelled with
      technetium-99m and indium-111; responsiveness of central serotonin 1A receptors
      measured by the prolactin release following challenge with oral buspirone 60 mg.
      RESULTS: Solid phase gastric emptying was significantly delayed in the patients
      with non-ulcer dyspepsia (t 1/2 = 90.6 (SD 14.5) minutes in patients and 54.6
      (10.7) minutes in controls; 95% confidence interval 24.7 to 46.7 minutes, p <
      0.001). Prolactin release was significantly greater in patients compared with
      controls (1272.7 (1039.9) mU/l v 292.9 (136.1) mU/l; 352.1 to 1607.5 mU/l, p <
      0.01). Gastric emptying and prolactin release were significantly correlated (r =
      0.59, p = 0.04) in the patients but not in the controls (r = 0.23). CONCLUSION:
      Central serotonin 1A receptors may have a role in the pathophysiology of non
      ulcer dyspepsia of the dysmotility subtype.

PMID- 1392860
TI  - Child pedestrian mortality and traffic volume in New Zealand.

PMID- 1392861
TI  - Health service support of breast feeding--are we practising what we preach?
AB  - OBJECTIVE: To ascertain the attitudes of health professionals and breast feeding
      mothers to breast feeding and their views on current practice. DESIGN:
      Questionnaire to all midwives and health visitors and to breast feeding mothers
      in Newcastle upon Tyne. SETTING: Maternity units and community in Newcastle upon
      Tyne. SUBJECTS: 127 hospital midwives, 23 community midwives, 63 health visitors,
      and 50 first time breast feeding mothers. RESULTS: Optimum practice guidelines
      were not followed. 30 (60%) mothers said they were separated from their babies on
      the first night after birth. 82 (42%) professionals said that breast fed babies
      were frequently given water to drink. 28 (56%) babies in the mothers survey had
      received food or water other than breast milk; 19 of these had been given water.
      Professionals expressed mainly positive attitudes towards breast feeding in
      general but less positive attitudes to specific issues such as the beneficial
      effects on child health and the value of voluntary organisations in breast
      feeding promotion and management. CONCLUSIONS: Although many health workers are
      in favour of breast feeding there is conflict among the professions working most
      closely with breast feeding mothers. Good breast feeding support requires closer
      attention to monitoring hospital practices and continued training on good
      lactation management.

PMID- 1392862
TI  - The clinical task.

PMID- 1392864
TI  - Russian report: perspectives on strikes by health care staff.

PMID- 1392863
TI  - Congenital toxoplasmosis.

PMID- 1392865
TI  - An infected prosthetic hip. Is there a role for prophylactic antibiotics?

PMID- 1392866
TI  - ABC of colorectal diseases. Colorectal trauma.

PMID- 1392867
TI  - Service increment for teaching and research.

PMID- 1392868
TI  - Treatment of natal cleft sinus.

PMID- 1392869
TI  - Home accidents in elderly people.

PMID- 1392870
TI  - Home accidents in elderly people.

PMID- 1392871
TI  - Monitoring Creutzfeldt-Jakob disease.

PMID- 1392872
TI  - Use of Lucozade and glucagon by ambulance staff in hypoglycaemia.

PMID- 1392873
TI  - Gall stones induced by octreotide.

PMID- 1392874
TI  - Assessing observer variability.

PMID- 1392875
TI  - Medical audit in general practice.

PMID- 1392876
TI  - Toxic dilatation and infective diarrhoea.

PMID- 1392877
TI  - Gene therapy.

PMID- 1392878
TI  - Withdrawal of a monopoly treatment.

PMID- 1392879
TI  - The special hospitals.

PMID- 1392880
TI  - Unawareness of hypoglycaemia and human insulin.

PMID- 1392881
TI  - "AIDS" without HIV: fire without smoke.

PMID- 1392882
TI  - Vitamin K and childhood cancer.

PMID- 1392883
TI  - Understanding schizophrenia.

PMID- 1392884
TI  - Nutrient intake and cataract extraction in women: a prospective study.
AB  - OBJECTIVE: To examine prospectively the association between dietary intake of
      vitamins C and E, carotene, and riboflavin and cataract extraction in women.
      DESIGN: Prospective cohort study beginning in 1980 with eight years of follow up.
      SETTING: 11 states of the United States. PARTICIPANTS: Female registered nurses
      who were 45 to 67 years of age. 50,828 women were included in 1980 and others
      were added as they became 45 years of age. MAIN OUTCOME MEASURE: Incidence of
      extraction of senile cataracts. RESULTS: 493 cataracts were extracted during
      470,302 person years of follow up. Intake of carotene and vitamin A was inversely
      associated with cataract: in multivariate analyses, women in the highest fifth of
      total vitamin A intake (excluding supplements) had a 39% lower risk of cataract
      relative to women in the lowest fifth (relative risk 0.61; 95% confidence
      interval 0.45 to 0.81). Neither riboflavin nor dietary vitamins E or C were
      associated with cataract in a multivariate analysis. Among specific food items
      spinach (rather than carrots, the greatest source of beta carotene) was most
      consistently associated with a lower relative risk. The risk of cataract was 45%
      lower among women who used vitamin C supplements for 10 or more years(relative
      risk 0.55 (0.32 to 0.96)), but no association was noted for multivitamin intake.
      CONCLUSION: Dietary carotenoids, although not necessarily beta carotene, and long
      term vitamin C supplementation may decrease the risk of cataracts severe enough
      to require extraction.

PMID- 1392885
TI  - Case holding in patients with tuberculosis in Botswana.
AB  - OBJECTIVE: To evaluate the effectiveness of daily supervised short course
      chemotherapy in a national tuberculosis programme. DESIGN: Observation of
      programme during 1984-90. In October 1986 short course chemotherapy was
      introduced with patients receiving treatment daily from staff in their nearest
      health facility. SETTING: Botswana national tuberculosis programme. SUBJECTS: All
      patients with tuberculosis. MAIN OUTCOME MEASURES: Proportions of patients
      complying with and defaulting from treatment (missing > or = 43 days' treatment).
      RESULTS: 2938 cases of tuberculosis were recorded in 1990, 1528 of which were of
      sputum positive pulmonary disease. 2711 (92.3%) patients complied with treatment
      and 227 (7.7%) defaulted. Before introduction of short course chemotherapy
      compliance was about 60% compared with over 90% in 1987-90. CONCLUSIONS: A
      programme using daily supervised short course chemotherapy integrated into the
      primary health care system is an effective method of treating tuberculosis. The
      costs of the programme need to be evaluated.

PMID- 1392886
TI  - Childhood cancer, intramuscular vitamin K, and pethidine given during labour.
AB  - OBJECTIVE: To assess unexpected associations between childhood cancer and
      pethidine given in labour and the neonatal administration of vitamin K that had
      emerged in a study performed in the 1970 national birth cohort. DESIGN AND
      SETTING: 195 children with cancer diagnosed in 1971-March 1991 and born in the
      two major Bristol maternity hospitals in 1965-87 were compared with 558 controls
      identified from the delivery books for the use of pethidine during labour and
      administration of vitamin K. MAIN OUTCOME MEASURES: Odds ratios for cancer in the
      presence of administration of pethidine or of intramuscular vitamin K. Both
      logistic regression and Mantel-Haenszel techniques were used for statistical
      analyses. RESULTS: Children of mothers given pethidine in labour were not at
      increased risk of cancer (odds ratio 1.05, 95% confidence interval 0.7 to 1.5)
      after allowing for year and hospital of delivery, but there was a significant
      association (p = 0.002) with intramuscular vitamin K (odds ratio 1.97, 95%
      confidence interval 1.3 to 3.0) when compared with oral vitamin K or no vitamin
      K. There was no significantly increased risk for children who had been given oral
      vitamin K when compared with no vitamin K (odds ratio 1.15, 95% confidence
      interval 0.5 to 2.7). These results could not be accounted for by other factors
      associated with administration of intramuscular vitamin K, such as type of
      delivery or admission to a special care baby unit. CONCLUSIONS: The only two
      studies so far to have examined the relation between childhood cancer and
      intramuscular vitamin K have shown similar results, and the relation is
      biologically plausible. The prophylactic benefits against haemorrhagic disease
      are unlikely to exceed the potential adverse effects from intramuscular vitamin
      K. Since oral vitamin K has major benefits but no obvious adverse effects this
      could be the prophylaxis of choice.

PMID- 1392888
TI  - Attached, detached, or new recruits?

PMID- 1392887
TI  - Fluoxetine treatment of severe premenstrual syndrome.

PMID- 1392889
TI  - Human insulin and unawareness of hypoglycaemia: need for a large randomised
      trial.

PMID- 1392890
TI  - ABC of colorectal diseases. Large bowel volvulus.

PMID- 1392891
TI  - Health of the nation.

PMID- 1392892
TI  - Health of the nation.

PMID- 1392893
TI  - Health of the nation.

PMID- 1392894
TI  - Promoting sexual health.

PMID- 1392895
TI  - Promoting sexual health.

PMID- 1392896
TI  - Promoting sexual health.

PMID- 1392897
TI  - Sexual contact in the doctor-patient relationship.

PMID- 1392898
TI  - Site of injection for vaccination.

PMID- 1392899
TI  - Outcome in the chronic fatigue syndrome.

PMID- 1392900
TI  - Outcome in the chronic fatigue syndrome.

PMID- 1392901
TI  - Outcome in the chronic fatigue syndrome.

PMID- 1392902
TI  - Dangers of aspirin before cardiac surgery.

PMID- 1392903
TI  - Selective serotonin reuptake inhibitors.

PMID- 1392904
TI  - HIV antibodies in babies.

PMID- 1392905
TI  - Treatment of Hodgkin's lymphoma.

PMID- 1392906
TI  - Unawareness of dystonia.

PMID- 1392907
TI  - Teaching vaginal examination.

PMID- 1392908
TI  - Teaching vaginal examination.

PMID- 1392909
TI  - Teaching vaginal examination.

PMID- 1392910
TI  - Teaching vaginal examination.

PMID- 1392911
TI  - Teaching vaginal examination.

PMID- 1392912
TI  - Exercise, fitness, and health.

PMID- 1392913
TI  - Epilepsy and stress.

PMID- 1392914
TI  - Should clofibrate still be prescribed?

PMID- 1392915
TI  - Medicine and torture.

PMID- 1392916
TI  - The death penalty.

PMID- 1392917
TI  - French blood trial finishes.

PMID- 1392918
TI  - Health status of the temporarily homeless population and residents of North West
      Thames region.
AB  - OBJECTIVES: To survey the health status of the temporarily homeless population of
      North West Thames region and make comparisons with regional residents. DESIGN:
      Direct interview with standardised questionnaires. SETTING: Temporarily homeless
      people resident in hotels in the London boroughs in the North West Thames region
      and a random sample of regional residents. SUBJECTS: 137 hotels thought to be
      providing accommodation to homeless people selected at random from a list of 295.
      113 (82%) participated in the study, and 319 (61%) of 522 homeless people
      approached participated. The study was restricted to adults aged 16 and over
      selected at random. RESULTS: The homeless population was predominantly female
      (195/319; 61%), young (229 (72%) aged 16-34), and poor, 54% (172/319) receiving
      income support. 207 subjects (65%) had dependent children aged 16 and under.
      Rates of acute illness among homeless people (32 cases; 10%) were similar to
      those reported by regional residents. The prevalence of longstanding limiting
      illness (108 cases; 34%) was similar to that for regional residents, but the
      prevalence of mental morbidity was twice that for the region as a whole (145
      cases (45%) v 1485 (18%)). Utilisation of general practitioner services, accident
      and emergency departments, and inpatient admission was much higher by the
      homeless population than by regional residents. General practitioner registration
      rates were above 90% for the homeless sample. CONCLUSIONS: Survey data provide
      empirical evidence about the nature and characteristics of the temporarily
      homeless population. The high service utilisation recorded may, in part, have
      resulted from the higher morbidity in this sample of homeless people. The
      concentration of homeless people into specific locations may suggest that
      additional funding should be provided to the district which provides care to this
      group. However, such funding should not necessarily be used for additional acute
      care but should be used to purchase appropriate services which meet the health
      needs of this very young, poor and vulnerable group.

PMID- 1392919
TI  - Laparoscopic cholecystectomy as a safe and effective treatment for severe acute
      cholecystitis.
AB  - OBJECTIVE: To evaluate the feasibility and safety of laparoscopic cholecystectomy
      in severe acute cholecystitis. DESIGN: Analysis of data collected prospectively
      from a consecutive series of 350 laparoscopic operations. SETTING: Two general
      surgical units in a teaching hospital. SUBJECTS: 31 patients with a diagnosis of
      severe acute cholecystitis based on clinical examination, investigation results,
      and operative findings. INTERVENTIONS: Initial intravenous fluids and broad
      spectrum antibiotics followed by laparoscopic cholecystectomy within 72 hours of
      presentation. MAIN OUTCOME MEASURES: Failure to complete the operation
      laparoscopically, length of postoperative stay in hospital, early postoperative
      morbidity, interval from operation to full activity, and return to work. RESULTS:
      Laparoscopic cholecystectomy was attempted in 19 patients with empyema of the
      gall bladder and 12 who had severe cholecystitis which failed to settle on
      medical management. A total of 29 operations were successfully completed with two
      conversions to open surgery. Two minor postoperative complications occurred, and
      one case of retained common bile duct stones with jaundice was treated by
      endoscopic retrograde cholangiopancreatography and papillotomy. Median
      postoperative hospital stay was two days, with return to normal activity in seven
      days and to work in two weeks. There were no deaths related to the operation.
      CONCLUSIONS: In the presence of severe acute cholecystitis laparoscopic
      cholecystectomy is feasible in most patients, with minimal risk of injury to
      surrounding structures and considerable benefits. It is recommended that
      laparoscopic cholecystectomy should be attempted in these patients when
      appropriate surgical skill is available.

PMID- 1392920
TI  - Asthma and open cast mining.

PMID- 1392921
TI  - BASDEC: a novel screening instrument for depression in elderly medical
      inpatients.

PMID- 1392922
TI  - General practice partnerships: till death us do part?
AB  - OBJECTIVES: To investigate applications for general practice partnership
      vacancies by established general practitioner principals, the reasons for
      changing partnerships, and the disincentives to these moves. DESIGN: Confidential
      postal questionnaire. SUBJECTS: Applicants to 367 general practices in the United
      Kingdom advertising for a new full time partner. MAIN OUTCOME MEASURES: The
      proportion of job applications containing at least one application from
      established principals, proportion of principals appointed as new partners,
      incentives and disincentives to changing partnership. RESULTS: Of 325 replies
      (89% response rate) received, 292 were suitable for further analysis. 210/241
      (87%) of all applications contained some applications from at least one
      established principal. 12% of all applications were made by principals. 41/296
      (14%) of the newly appointed partners had previously been an established
      principal. The main reasons for leaving the previous partnership were a desire to
      move locality or not getting on with previous partners. The disincentives to
      changing partnerships were largely financial, including the cost of the move and
      loss of income. CONCLUSIONS: It is possible for established principals in general
      practice to overcome the disincentives and to change partnerships. There did not
      seem to be any overall prejudice against appointing principals, in contrast to
      previously published views.

PMID- 1392923
TI  - Caring for the future.

PMID- 1392924
TI  - Health care for the elderly in Japan: medicine and welfare in an aging society
      facing a crisis in long term care.

PMID- 1392925
TI  - Consensus on general medical contraindications to organ donation?

PMID- 1392926
TI  - ABC of colorectal diseases. Pilonidal sinus.

PMID- 1392927
TI  - Design a clinical information system.

PMID- 1392928
TI  - Early parenteral penicillin in meningococcal disease.

PMID- 1392929
TI  - Early parenteral penicillin in meningococcal disease.

PMID- 1392930
TI  - Early parenteral penicillin in meningococcal disease.

PMID- 1392931
TI  - Frequency of citation and outcome of cholesterol lowering trials.

PMID- 1392932
TI  - Frequency of citation and outcome of cholesterol lowering trials.

PMID- 1392934
TI  - Frequency of citation and outcome of cholesterol lowering trials.

PMID- 1392933
TI  - Frequency of citation and outcome of cholesterol lowering trials.

PMID- 1392936
TI  - Cardiopulmonary resuscitation in British hospitals.

PMID- 1392935
TI  - Adenosine and cardiac arrhythmias.

PMID- 1392937
TI  - Cardiopulmonary resuscitation in British hospitals.

PMID- 1392938
TI  - Cardiopulmonary resuscitation in British hospitals.

PMID- 1392939
TI  - Cardiopulmonary resuscitation in British hospitals.

PMID- 1392940
TI  - Cardiopulmonary resuscitation in British hospitals.

PMID- 1392941
TI  - Reprocessing data to form QALYs.

PMID- 1392942
TI  - Causes of lower gastrointestinal haemorrhage.

PMID- 1392943
TI  - Notifying contacts of people with HIV infection.

PMID- 1392944
TI  - EC directives on medical devices.

PMID- 1392945
TI  - Health technology assessment.

PMID- 1392946
TI  - Therapy for people with learning difficulties.

PMID- 1392947
TI  - Tobacco advertising.

PMID- 1392949
TI  - Respiratory medicine: fighting for survival.

PMID- 1392948
TI  - Diarrhoea, dysentery, and food poisoning.

PMID- 1392950
TI  - Suing tobacco industry for damages.

PMID- 1392951
TI  - Future of human milk banks.

PMID- 1392952
TI  - Improving the care of elderly people.

PMID- 1392953
TI  - Diagnosing congenital dislocation of the hip.

PMID- 1392954
TI  - Abortion in Ireland.

PMID- 1392955
TI  - Discomfort and pain during mammography: description, prediction, and prevention.
AB  - OBJECTIVE: To identify the nature of pain and discomfort experienced during
      mammography and how it can be ameliorated. DESIGN: Questionnaire survey before
      invitation for mammography and immediately after mammography. Responses before
      screening were related to experience of discomfort. SETTING: Health district in
      South East Thames region. SUBJECTS: 1160 women aged 50-64 invited routinely for
      screening; 774 completed first questionnaire, of whom 617 had mammography. 597
      completed the second questionnaire. MAIN OUTCOME MEASURES: Reported discomfort
      and pain, comparisons of discomfort with that experienced during other medical
      procedures, qualitative description of pain with adjective checklist. RESULTS:
      35% (206/597) of the women reported discomfort and 6% (37/595) pain. 10 minutes
      after mammography these figures were 4% (24/595) and 0.7% (4/595) respectively.
      More than two thirds of women ranked having a tooth drilled, having a smear test,
      and giving blood as more uncomfortable than mammography. The most important
      predictor of discomfort was previous expectation of pain (discomfort was reported
      by 21/32 (66%) women who expected pain and 186/531 (35%) who did not). Discomfort
      had little effect on satisfaction or intention to reattend. CONCLUSIONS: The low
      levels of reported pain and discomfort shortly after mammography and the
      favourable comparisons with other investigations suggest that current procedures
      are acceptable. Since two thirds of the women experienced less pain than expected
      health education and promotion must ensure that accurate information is made
      available and publicized.

PMID- 1392956
TI  - Time delays in provision of thrombolytic treatment in six district hospitals.
      Joint Audit Committee of the British Cardiac Society and a Cardiology Committee
      of Royal College of Physicians of London.
AB  - OBJECTIVE: To measure the delays between onset of symptoms and admission to
      hospital and provision of thrombolysis in patients with possible acute myocardial
      infarction. DESIGN: Observational study of patients admitted with suspected
      myocardial infarction during six months. SETTING: Six district general hospitals
      in Britain. SUBJECTS: 1934 patients admitted with suspected myocardial
      infarction. MAIN OUTCOME MEASURES: Route of admission to hospital and time to
      admission and thrombolysis. RESULTS: Patients who made emergency calls did so
      sooner after onset of symptoms than those who called their doctor (median time 40
      (95% confidence interval 30 to 52) minutes v 70 (60 to 90) minutes). General
      practitioners took a median of 20 (20 to 25) minutes to visit patients, rising to
      30 (20 to 30) minutes during 0800-1200. The median time from call to arrival in
      hospital was 41 (38 to 47) minutes for patients who called an ambulance from home
      and 90 (90 to 94) minutes for those who contacted their doctor. The median time
      from arrival at hospital to thrombolysis was 80 (75 to 85) minutes for patients
      who were treated in the cardiac care unit and 31 (25 to 35) minutes for those
      treated in the accident and emergency department. CONCLUSION: The time from onset
      of symptoms to thrombolysis could be reduced substantially by more effective use
      of emergency services and faster provision of thrombolysis in accident and
      emergency departments.

PMID- 1392957
TI  - Predicting mortality from cervical cancer after negative smear test results.
AB  - OBJECTIVE: To assess the relative protection against death from cervical cancer
      after two or more negative smear test results and compare it with the protection
      against invasive cancer estimated by an International Agency for Research on
      Cancer (IARC) working group in an analysis of data from 10 large screening
      programmes. DESIGN: Comparison of risk of death from cervical cancer after two or
      more negative smear results with the risk in unscreened women by using a model
      constructed with data from the British Columbia screening programme. MAIN OUTCOME
      MEASURES: Mortality from and incidence of invasive cancer. RESULTS: In women with
      two negative smear results estimates of protection against cervical cancer were
      about 50% higher when lethal invasive cancer was used as the criterion rather
      than all invasive cancer. This difference was due to these women being more
      likely to attend for further tests at which invasive cancer could be detected:
      screen detected cancer has a better prognosis than clinically diagnosed cancer.
      Screening intervals could be longer than three years: screening women aged 35-64
      every five years was predicted to result in a 90% reduction in mortality from
      cervical cancer. CONCLUSION: Because protection from mortality is higher than
      protection from disease and because of the high costs and negative side effects
      of frequent screening, screening intervals should be longer than three years.

PMID- 1392958
TI  - Endocrine adverse effects of omeprazole.

PMID- 1392959
TI  - Myelopathy associated with human T cell lymphotropic virus type 1 in a white
      European native to England.

PMID- 1392960
TI  - Management and administration.

PMID- 1392961
TI  - Psychosocial factors, cancer, and ischaemic heart disease.

PMID- 1392962
TI  - Prepare for a foreign fellow.

PMID- 1392963
TI  - ABC of colorectal diseases. Paediatric problems--I.

PMID- 1392964
TI  - Quality of life: philosophical question or clinical reality?

PMID- 1392965
TI  - Classifying suicide.

PMID- 1392966
TI  - Lipoprotein(a) and coronary heart disease.

PMID- 1392967
TI  - Value of Dundee coronary risk-disk.

PMID- 1392968
TI  - Value of Dundee coronary risk-disk.

PMID- 1392969
TI  - Contamination of skin and clothing of A and E staff.

PMID- 1392970
TI  - Midwifery and body fluid contamination.

PMID- 1392971
TI  - Midwifery and body fluid contamination.

PMID- 1392972
TI  - Personal protective equipment for employees.

PMID- 1392973
TI  - Exposure to radon.

PMID- 1392974
TI  - When to stop a clinical trial.

PMID- 1392975
TI  - When to stop a clinical trial.

PMID- 1392976
TI  - Poliomyelitis in developing countries.

PMID- 1392977
TI  - Women's preference for place of birth.

PMID- 1392978
TI  - Women's preference for place of birth.

PMID- 1392979
TI  - Epidural analgesia and backache.

PMID- 1392980
TI  - Is duplicate publishing on the increase?

PMID- 1392981
TI  - Osteoarthritis of the hip in farmers.

PMID- 1392982
TI  - Bibliography on cot death needed.

PMID- 1392983
TI  - Dispensing doctors.

PMID- 1392984
TI  - Victims of Creutzfeldt-Jakob disease.

PMID- 1392986
TI  - Disposal of used metered dose inhalers.

PMID- 1392985
TI  - Emergency treatment against a patient's wishes.

PMID- 1392987
TI  - Mixed psychiatric wards.

PMID- 1392988
TI  - Poor Britain.

PMID- 1392989
TI  - Vaccination against Haemophilus influenzae b disease.

PMID- 1392990
TI  - Managing the persistent vegetative state.

PMID- 1392991
TI  - Balloon dilatation of heart valves.

PMID- 1392992
TI  - Reaccrediting general practice.

PMID- 1392993
TI  - Osteoporosis in men.

PMID- 1392994
TI  - BCG immunisation in England and Wales: a survey of policy and practice in
      schoolchildren and neonates.
AB  - OBJECTIVE: To determine the policy and practice of district health authorities in
      England and Wales for BCG immunisation in schoolchildren and neonates. DESIGN:
      Self completion postal questionnaire survey. PARTICIPANTS: District immunisation
      coordinators. SETTING: 199 district health authorities in England and Wales.
      RESULTS: Questionnaires were received from 186 districts, a response rate of 94%.
      Considerable uniformity was observed in many aspects of BCG immunisation policy
      and practice but some important variations were found. 15 districts no longer
      carry out a routine schools programme. 148 districts offer BCG to selected groups
      of neonates and five to all neonates, but 31 districts do not offer BCG to this
      age group. The recommended action in response to different levels of tuberculin
      sensitivity in schoolchildren and neonates varied among districts. CONCLUSIONS:
      Despite the recommendations of the Joint Committee on Vaccination and
      Immunisation some districts do not offer BCG immunisation to neonates at high
      risk of tuberculosis and there are important variations in other aspects of BCG
      policy.

PMID- 1392995
TI  - Randomised controlled trial of short term treatment to eradicate Helicobacter
      pylori in patients with duodenal ulcer.
AB  - OBJECTIVE: To determine whether one week's drug treatment is sufficient to
      eradicate Helicobacter pylori in patients with duodenal ulcer. DESIGN: Single
      blind, randomised controlled trial. SETTING: Specialised ulcer clinic in a
      teaching hospital. PATIENTS: 155 patients with H pylori and a duodenal ulcer
      verified endoscopically which had either bled within the previous 24 hours or was
      causing dyspepsia. INTERVENTIONS: Patients were allocated randomly to receive
      either omeprazole for four weeks plus bismuth 120 mg, tetracycline 500 mg, and
      metronidazole 400 mg (all four times a day) for the first week (n = 78), or
      omeprazole alone for four weeks (n = 77). Further endoscopy was performed four
      weeks after cessation of all drugs. MAIN OUTCOME MEASURES: Presence or absence of
      H pylori (by urease testing, microscopy, and culture of antral biopsy specimens),
      duodenal ulcer, and side effects. RESULTS: Eradication of H pylori occurred in 70
      (95%) patients taking the four drugs (95% confidence interval 86% to 97%)
      compared with three (4%) patients taking omeprazole alone (1% to 11%). Duodenal
      ulcers were found in four (5%) patients taking the four drugs (2% to 12%) and in
      16 (22%) patients taking omeprazole alone (14% to 32%). Mild dizziness was the
      only reported side effect (six patients in each group) and did not affect
      compliance. CONCLUSIONS: A one week regimen of bismuth, tetracycline, and
      metronidazole is safe and effective in eradicating H pylori and reduces the
      number of duodenal ulcers four weeks after completing treatment.

PMID- 1392996
TI  - Fibrinolytic balance and lupus anticoagulant in patients with repeated
      spontaneous fetal loss.

PMID- 1392997
TI  - Partners in practice. Getting better: education and the primary health care team.

PMID- 1392998
TI  - "Breathing" coal mines and surface asphyxiation from stythe (black damp).

PMID- 1392999
TI  - ABC of colorectal diseases. Paediatric problems--II.

PMID- 1393000
TI  - "Mind the gap": reflections of an American health maintenance organisation doctor
      on the new NHS.

PMID- 1393001
TI  - Wernicke's encephalopathy and central pontine myelinolysis associated with
      hyperemesis gravidarum.

PMID- 1393002
TI  - Screening, ethics, and the law.

PMID- 1393003
TI  - Screening, ethics, and the law.

PMID- 1393004
TI  - Fluid replacement in diabetic ketoacidosis.

PMID- 1393005
TI  - Human insulin and unawareness of hypoglycemia.

PMID- 1393006
TI  - Poisoning and child resistant containers.

PMID- 1393007
TI  - Health service support of breast feeding.

PMID- 1393008
TI  - Health service support of breast feeding.

PMID- 1393009
TI  - Health service support of breast feeding.

PMID- 1393010
TI  - Health service support of breast feeding.

PMID- 1393011
TI  - Early parenteral penicillin in meningococcal disease.

PMID- 1393012
TI  - Giant cell arteritis.

PMID- 1393013
TI  - Removal of central venous catheter and venous air embolism.

PMID- 1393014
TI  - Detecting severe silent mitral regurgitation.

PMID- 1393015
TI  - Removal of central venous catheter and venous air embolism.

PMID- 1393016
TI  - Trends in cerebral palsy in Western Australia.

PMID- 1393017
TI  - Trends in cerebral palsy in Western Australia.

PMID- 1393018
TI  - Selective serotonin reuptake inhibitors.

PMID- 1393020
TI  - Disintegration of civilian life in Myanmar.

PMID- 1393019
TI  - Value of the Dundee coronary risk-disk.

PMID- 1393021
TI  - DNA fingerprinting and contact tracing.

PMID- 1393022
TI  - Patient's charter in outpatient services.

PMID- 1393024
TI  - Induction of house officers.

PMID- 1393023
TI  - Induction of house officers.

PMID- 1393025
TI  - Primary health care teams.

PMID- 1393026
TI  - Role of Western public health in "New World order".

PMID- 1393028
TI  - Local voices. The bankruptcy of the democratic process.

PMID- 1393027
TI  - Compulsory admission of dangerous psychopaths.

PMID- 1393029
TI  - Day surgery for cataracts.

PMID- 1393030
TI  - Liver fibrosis.

PMID- 1393031
TI  - Reducing aortocaval compression: how much tilt is enough?

PMID- 1393032
TI  - Social effects of wheeze in childhood: a 25 year follow up.
AB  - OBJECTIVES: To determine the outcome of childhood wheeze in terms of education,
      employment, housing, and social class. DESIGN: 25 year follow up study. SETTING:
      Community study based at the department of thoracic medicine, Aberdeen Royal
      Infirmary. PARTICIPANTS: Three groups of subjects who had been identified in a
      random community survey in 1964: those who had had asthma in childhood (n = 97),
      those who had wheezed only in the presence of upper respiratory tract infections
      (n = 132), and a comparison group who had had no respiratory symptoms as children
      (n = 131). Subjects were aged 34 to 40 years at the time of the current study.
      MAIN OUTCOME MEASURES: Interview and questionnaire data on education, employment,
      housing and social class, ventilatory function, and peak flow rate. RESULTS:
      Pulmonary function testing showed that only the "asthmatic" group had airways
      obstruction; this group showed greater peak flow variation than the "wheezy"
      group, which did not differ from the comparison group. The asthmatic subjects
      were more likely to have experienced respiratory problems during their school
      years and associated with their work. Despite these problems, educational
      attainment, employment, housing, and eventual social class were similar for all
      three groups. CONCLUSION: Childhood wheeze did not adversely affect education,
      employment, housing, or social class in this population.

PMID- 1393033
TI  - Feasibility, safety, and efficacy of domiciliary thrombolysis by general
      practitioners: Grampian region early anistreplase trial. GREAT Group.
AB  - OBJECTIVE: To assess the feasibility, safety, and efficacy of domiciliary
      thrombolysis by general practitioners. DESIGN: Randomised double blind parallel
      group trial of anistreplase 30 units intravenously and placebo given either at
      home or in hospital. SETTING: 29 rural practices in Grampian admitting patients
      to teaching hospitals in Aberdeen (average distance 36 (range 16-62) miles).
      PATIENTS: 311 patients with suspected acute myocardial infarction and no
      contraindications to thrombolytic therapy seen at home within four hours of onset
      of symptoms. MAIN OUTCOME MEASURES: Time saving, adverse events, Q wave
      infarction, left ventricular function. RESULTS: Anistreplase was administered at
      home 101 minutes after onset of symptoms, while anistreplase was given in
      hospital 240 minutes after onset of symptoms (median times). Adverse events after
      thrombolysis were infrequent and, apart from cardiac arrest, not a serious
      problem when they occurred in the community: seven of 13 patients were
      resuscitated after cardiac arrest out of hospital. By three months after trial
      entry the relative reduction of deaths from all causes in patients given
      thrombolytic therapy at home was 49% (13/163 (8.0%) v 23/148 (15.5%); difference 
      7.6% (95% confidence interval -14.7% to -0.4%), p = 0.04). Full thickness Q wave
      infarction was less common in patients with confirmed infarction receiving
      treatment at home (65/122 (53.3%) v 76/112 (67.9%); difference -14.6% (95%
      confidence interval -27.0% to -2.2%), p = 0.02). CONCLUSIONS: General
      practitioners provided rapid pre-hospital coronary care of a high standard.
      Compared with later administration in hospital, giving anistreplase at home
      resulted in reduction in mortality, fewer cardiac arrests, fewer Q wave infarcts,
      and better left ventricular function. Benefits were most marked where
      thrombolytic therapy was administered within two hours of the onset of symptoms.

PMID- 1393034
TI  - Safety of early pain relief for acute abdominal pain.
AB  - OBJECTIVES: (a) to determine the efficacy of papaveretum in treating pain when
      administered early to patients presenting with acute abdominal pain and (b) to
      assess its effect on subsequent diagnosis and management. DESIGN: Prospective,
      randomised, placebo controlled study. SETTING: Walsgrave Hospital, Coventry.
      SUBJECTS: 100 consecutive patients with clinically significant abdominal pain who
      were admitted as emergencies to a surgical firm. INTERVENTIONS: Intramuscular
      injection of up to 20 mg papaveretum or an equivalent volume of saline. OUTCOME
      MEASURES: Pain and tenderness scores, assessment of patient comfort, accuracy of
      diagnosis, and management decisions. RESULTS: Median pain and tenderness scores
      were lower after papaveretum (pain score 8.3 in control group and 3.1 in
      treatment group, p < 0.0001; tenderness score 8.1 in control group and 5.1 in
      treatment group, p < 0.0001). Forty eight patients were deemed to be comfortable
      after papaveretum compared with nine after saline. Incorrect diagnoses and
      management decisions applied to two patients after papaveretum compared with nine
      patients after saline. CONCLUSION: Early administration of opiate analgesia to
      patients with acute abdominal pain can greatly reduce their pain. This does not
      interfere with diagnosis, which may even be facilitated despite a reduction in
      the severity of physical signs. These patients should not be denied effective
      treatment.

PMID- 1393035
TI  - Effect of salcatonin given intranasally on bone mass and fracture rates in
      established osteoporosis: a dose-response study.
AB  - OBJECTIVE: To study the dose related response of salmon calcitonin (salcatonin)
      given intranasally on bone mass and bone turnover and the effect of salcatonin on
      rates of fracture in elderly women with moderate osteoporosis. DESIGN: Double
      blind, placebo controlled, randomised group comparison. SETTING: Outpatient
      clinic for research into osteoporosis. SUBJECTS: 208 healthy women aged 68-72
      years who had a bone mineral content of the distal forearm on average 30% below
      the mean value for healthy premenopausal women. INTERVENTIONS: The 208 women were
      allocated randomly in blocks of four to two years of treatment with either
      salcatonin 50 IU, 100 IU, or 200 IU given intranasally or placebo. All groups
      received a calcium supplement of 500 mg. 32 of the women left the study before
      its end and 164 women complied with the study criteria throughout. MAIN OUTCOME
      MEASURES: Bone mineral content of the distal forearm and lumbar spine and rates
      of vertebral and peripheral fractures after two years of treatment. RESULTS: The
      average changes in bone mineral content of the spine showed positive outcomes of
      1% (95% confidence interval -0.1% to 1.5%) in the group treated with calcium
      (placebo) and 3% (1.8% to 4.2%) in the group treated with salcatonin 200 IU.
      There was a significant dose related response to salcatonin, manifested by an
      increase of 1.0%/100 IU (0.2% to 1.7%, p = 0.008). The rate of patients with new
      fractures was reduced significantly in the women treated with salcatonin to about
      one third of that in the non-salcatonin treated women (relative risk 0.23 (0.07
      to 0.77)). CONCLUSION: The results suggest that, compared with calcium alone,
      salcatonin given intranasally reduces the rates of fracture by two thirds in
      elderly women with moderate osteoporosis. Furthermore, it increases spinal bone
      mass in a dose dependent manner.

PMID- 1393036
TI  - HIV infection in a cohort of homosexual and bisexual men.

PMID- 1393037
TI  - Relation of serum sialic acid to lipid concentrations.

PMID- 1393038
TI  - Treatment with activated charcoal complicated by gastrointestinal obstruction
      requiring surgery.

PMID- 1393039
TI  - Beyond the boundaries: relationship between general practice and complementary
      medicine.

PMID- 1393040
TI  - ABC of colorectal diseases. Pruritus ani.

PMID- 1393041
TI  - Cutting queues or cutting corners: waiting lists and the 1990 NHS reforms.

PMID- 1393042
TI  - Does the patient know best?

PMID- 1393043
TI  - Does the patient know best?

PMID- 1393044
TI  - Does the patient know best?

PMID- 1393045
TI  - Does the patient know best?

PMID- 1393046
TI  - 'Barfly' injuries.

PMID- 1393047
TI  - Oesophageal achalasia mistaken for anorexia nervosa.

PMID- 1393048
TI  - Value of routine ultrasound scanning.

PMID- 1393049
TI  - Value of routine ultrasound scanning.

PMID- 1393050
TI  - Value of routine ultrasound scanning.

PMID- 1393051
TI  - Adjuvant therapy for rectal cancer.

PMID- 1393052
TI  - Americans retreat on SI units.

PMID- 1393053
TI  - Americans retreat on SI units.

PMID- 1393054
TI  - Serotonin, gastric emptying, and dyspepsia.

PMID- 1393056
TI  - Provident associations and medical fees.

PMID- 1393055
TI  - Promoting sexual health.

PMID- 1393057
TI  - London's health care.

PMID- 1393058
TI  - Cigarette taxation and single European market.

PMID- 1393059
TI  - London's health care.

PMID- 1393060
TI  - SIFTR, London, and district general hospitals.

PMID- 1393061
TI  - Assessing GP trainees.

PMID- 1393063
TI  - Treating Jehovah's Witnesses.

PMID- 1393062
TI  - Public health heresy.

PMID- 1393064
TI  - AIDS farewells.

PMID- 1393065
TI  - Avoiding iatrogenic injuries in theatre.

PMID- 1393066
TI  - Emergency feeding programmes.

PMID- 1393067
TI  - Registering a need.

PMID- 1393068
TI  - Large volume plastic spacers in asthma.

PMID- 1393069
TI  - Thyroid cancer rises after Chernobyl.

PMID- 1393070
TI  - Living will allows choice of medical care.

PMID- 1393071
TI  - Simulation model for planning renal services in a district health authority.
AB  - OBJECTIVE: To investigate the use of a computer simulation model in planning and
      budgeting for renal replacement services. SETTING: Regional renal unit. RESULTS:
      The simulation provided projections that accurately reflected the actual numbers
      of people maintained on different forms of renal replacement therapy in previous
      years. Projections up to the end of the century showed that with no change in the
      demand for the service the total number of people on the renal replacement
      programme would increase by 40%. Increasing the uptake of new patients from 40
      per million to 55 per million would mean an increase of 66% in patient numbers
      over the same period. Similarly, at present day prices the cost of providing the
      service would rise by 31% with no change in demand and by twice this with the
      greater uptake of new patients. Increasing the number of transplant operations
      was shown to offer little prospect of a reduction in these costs. CONCLUSION: The
      simulation program could be used by individual renal units to evaluate different
      treatment policies and to budget for resource use. Even at current demand levels
      resource requirements for renal replacement therapy will continue to grow until
      after the end of the century.

PMID- 1393074
TI  - Warming lignocaine to reduce pain associated with injection.
AB  - OBJECTIVE: To investigate the effect of warming lignocaine on the pain associated
      with subcutaneous injection. DESIGN: Double blind, randomised, crossover study.
      SETTING: Hospital clinic. SUBJECTS: 40 healthy volunteers. INTERVENTIONS:
      Subcutaneous injection with 1 ml of 1% lignocaine at 20 degrees C and 1 ml of 1%
      lignocaine at 37 degrees C. MAIN OUTCOME MEASURES: Pain assessed by linear
      analogue pain scores and subjects' comparison of pain on injection. RESULTS: 25
      subjects (89%; 95% confidence interval 72% to 98%) thought that lignocaine at 20
      degrees C was more painful and 3 (11%; 2% to 28%) thought that lignocaine at 37
      degrees C was more painful (p < 0.0001); 12 subjects did not express a
      difference. Median pain score for injection at 20 degrees C was 11.00 and at 37
      degrees C was 3.25 (p < 0.001). Median difference was 8.25 (4.00 to 13.50).
      CONCLUSIONS: The simple procedure of warming to 37 degrees C reduced the pain
      associated with subcutaneous injection of lignocaine.

PMID- 1393073
TI  - Metabolic acidosis and fatal myocardial failure after propofol infusion in
      children: five case reports.
AB  - OBJECTIVE: To examine the possible contribution of sedation with propofol in the
      deaths of children who were intubated and required intensive care. DESIGN: Case
      note review. SETTING: Three intensive care units. SUBJECTS: Five children with
      upper respiratory tract infections aged between 4 weeks and 6 years. RESULTS:
      Four patients had laryngotracheo-bronchitis and one had bronchiolitis. All were
      sedated with propofol. The clinical course in all five cases was remarkably
      similar: an increasing metabolic acidosis was associated with brady-arrhythmia
      and progressive myocardial failure, which did not respond to resuscitative
      measures. All children developed lipaemic serum after starting propofol. These
      features are not usually associated with respiratory tract infections. No
      evidence was found of viral myocarditis, which was considered as a possible cause
      of death. CONCLUSION: Although the exact cause of death in these children could
      not be defined, propofol may have been a contributing factor.

PMID- 1393072
TI  - Evidence for decreasing quality of semen during past 50 years.
AB  - OBJECTIVE: To investigate whether semen quality has changed during the past 50
      years. DESIGN: Review of publications on semen quality in men without a history
      of infertility selected by means of Cumulated Index Medicus and Current List
      (1930-1965) and MEDLINE Silver Platter database (1966-August 1991). SUBJECTS:
      14,947 men included in a total of 61 papers published between 1938 and 1991. MAIN
      OUTCOME MEASURES: Mean sperm density and mean seminal volume. RESULTS: Linear
      regression of data weighted by number of men in each study showed a significant
      decrease in mean sperm count from 113 x 10(6)/ml in 1940 to 66 x 10(6)/ml in 1990
      (p < 0.0001) and in seminal volume from 3.40 ml to 2.75 ml (p = 0.027),
      indicating an even more pronounced decrease in sperm production than expressed by
      the decline in sperm density. CONCLUSIONS: There has been a genuine decline in
      semen quality over the past 50 years. As male fertility is to some extent
      correlated with sperm count the results may reflect an overall reduction in male
      fertility. The biological significance of these changes is emphasised by a
      concomitant increase in the incidence of genitourinary abnormalities such as
      testicular cancer and possibly also cryptorchidism and hypospadias, suggesting a
      growing impact of factors with serious effects on male gonadal function.

PMID- 1393075
TI  - Purging with paracetamol: report of four cases.

PMID- 1393076
TI  - Health checks on patients 75 years and over in Nottinghamshire after the new GP
      contract.
AB  - OBJECTIVE: To investigate annual health checks for patients of 75 years and over
      required by the 1990 contract for general practitioners. DESIGN: Visits to
      practices to collect information on how assessments were organised and carried
      out; completion of questionnaires for every patient who had been assessed in a
      sample month, using information provided by the practice records. SETTING: 20
      general practices in one family health services authority. SUBJECTS: Patients of
      75 years and over in 20 general practices. RESULTS: Three practices (15%) had not
      performed checks. Thirteen practices sent a letter to invite patients to undergo
      a check. Of these practices, seven followed up non-responders. Two practices
      visited patients' homes unannounced, and two did checks on an opportunistic basis
      only. Sixteen practices used a checklist. Sixteen practices involved their
      practice nurses; at eight of these, doctors also performed checks; in six
      practices the nurses undertaking the checks had no training in assessing old
      people. Ten practices assessed more than 75% of their old people in the first
      year of the new contract. Practices that did not follow up patients who had not
      responded to the invitation for assessment completed significantly fewer checks.
      During the sample month, 331 patients were assessed in the 17 practices. 204 new
      problems were discovered in 143 patients. Significantly more problems per patient
      were found in inner city areas. CONCLUSIONS: The way health checks were performed
      varied greatly, both in their organisation and the practices' attitudes. Many old
      people did not respond to letters asking if they wanted an assessment but very
      few refused one if followed up. Forty three per cent of those assessed had some
      unmet need. The number of new problems found per patient may reduce over the next
      few years if the assessments are successful. The need for annual assessment
      should be kept under review and adequate resources made available for the needs
      uncovered. Improved training for practice nurses in assessment is needed.
      Effectiveness of the checks must be monitored. If most unmet need falls in
      particular high risk groups it would seem sensible to modify the annual check to
      target these groups.

PMID- 1393077
TI  - Assessment of patients aged over 75 in general practice.
AB  - OBJECTIVES: To evaluate the assessment scheme for people aged 75, to establish
      doctors' and nurses' views on the value of the assessment scheme, and to seek
      patients' opinions on elderly assessments. DESIGN: Data on the assessment process
      were collected from individual practices. Questionnaires were sent to doctors and
      practice nurses undertaking assessments and to a sample of elderly patients.
      SUBJECTS: 31,565 patients aged 75 and over and all doctors registered with
      Wiltshire Family Health Services Authority, as well as practice nurses assessing
      elderly patients. A 2% random sample of elderly patients was selected to answer
      questions on patient satisfaction. MAIN OUTCOME MEASURES: Numbers of patients
      accepting the invitation for assessment, who carried out the assessments and
      where, what unmet needs were identified, and by whom. RESULTS: 20,192 patients
      (64%) accepted the assessment offer. Doctors carried out 8786 assessments and
      nurses 10,779. Although 12,317 (61%) were carried out in the home, nurses did
      most domiciliary assessments (7122/11,883). Nurses with extra qualifications
      identified the highest number of unmet needs (400/1000 visits). 155 of 228 (68%)
      doctors thought assessments unnecessary whereas 25 of 48 (52%) of nurses thought
      them important. 93% of patients found assessment useful. CONCLUSIONS: Doctors see
      no merit in the scheme; most undertake assessments opportunistically and pick up
      few new problems. Nurses who see it as important require further training to fit
      them to do home visits confidently. Patients who were assessed found it worth
      while. The case for developing a specialist community nurse for elderly people
      should be investigated.

PMID- 1393078
TI  - The developing primary care partnership.

PMID- 1393079
TI  - Set up a newsletter.

PMID- 1393080
TI  - ABC of colorectal diseases. Tropical colonic diseases.

PMID- 1393081
TI  - Asthma and open cast mining.

PMID- 1393082
TI  - Asthma and open cast mining.

PMID- 1393083
TI  - Exercise, fitness, and health.

PMID- 1393084
TI  - Validating the SF-36.

PMID- 1393085
TI  - Respiratory medicine: the casualties.

PMID- 1393086
TI  - AIDS and ethics in Birmingham.

PMID- 1393087
TI  - HIV infection and certification of death.

PMID- 1393088
TI  - Litigation over illness associated with tryptophan is possible.

PMID- 1393089
TI  - HIV infection and certification of death.

PMID- 1393090
TI  - Over the counter treatment for candidiasis.

PMID- 1393091
TI  - Screening for depression in elderly patients.

PMID- 1393092
TI  - Treatment of natal cleft sinus.

PMID- 1393093
TI  - Perineal tears.

PMID- 1393094
TI  - Self help organization's advice on myalgic encephalomyelitis.

PMID- 1393095
TI  - Using cytokines.

PMID- 1393096
TI  - Cardiac rehabilitation programmes.

PMID- 1393097
TI  - Dispensing doctors.

PMID- 1393098
TI  - Doctor's legal position in medical emergencies.

PMID- 1393099
TI  - Eradication of poliomyelitis.

PMID- 1393100
TI  - Nurses' access to subjects for research.

PMID- 1393101
TI  - Congenital toxoplasmosis.

PMID- 1393102
TI  - Advice on health care workers infected with HIV.

PMID- 1393103
TI  - Asian doctors and training in general practice.

PMID- 1393104
TI  - Contact tracing in HIV infection.

PMID- 1393105
TI  - Irradiation of assistants' hands.

PMID- 1393106
TI  - Specialist medical training and the European Community.

PMID- 1393107
TI  - Diagnosing maxillary sinusitis.

PMID- 1393108
TI  - Transfusing Yersinia enterocolitica.

PMID- 1393109
TI  - The molecular genetics of schizophrenia.

PMID- 1393110
TI  - The allure of genetic explanations.

PMID- 1393111
TI  - Retinal blood flow in diabetic retinopathy.
AB  - OBJECTIVES: (a) To report on the basic parameters of retinal blood flow in a
      population of diabetic patients with and without retinopathy and non-diabetic
      controls; (b) to formulate a haemodynamic model for the pathogenesis of diabetic
      retinopathy from this and other studies. DESIGN: Laser-Doppler velocimetry and
      computerised image analysis to determine retinal blood flow in a large cross
      sectional study. SETTING: Diabetic retinopathy outpatient clinic. SUBJECTS: 24
      non-diabetic controls and 76 diabetic subjects were studied (63 patients with
      insulin dependent diabetes, 13 with non-insulin dependent diabetes). Of the
      diabetic subjects, 12 had no diabetic retinopathy, 27 had background retinopathy,
      13 had pre-proliferative retinopathy, 12 had proliferative retinopathy, and 12
      had had pan-retinal photocoagulation for proliferative retinopathy. MAIN OUTCOME
      MEASURES: Retinal blood flow (microliters/min) and conductance (rate of flow per
      unit of perfusion pressure). RESULTS: In comparison with non-diabetic controls
      (9.52 microliters/min) and diabetic patients with no diabetic retinopathy (9.12
      microliters/min) retinal blood flow was significantly increased in all grades of
      untreated diabetic retinopathy (background 12.13 microliters/min, pre
      proliferative 15.27 microliters/min, proliferative 13.88 microliters/min). There
      was a significant decrease in flow after pan-retinal photocoagulation in
      comparison with all the other groups studied (4.48 microliters/min). Conductance
      of the retinal circulation was higher in the untreated diabetic retinopathy
      groups. These results were independent of age, sex, type of diabetes, duration of
      diabetes, glycated haemoglobin concentration, blood glucose concentration, blood
      pressure, and intraocular pressure. CONCLUSIONS: Retinal blood flow is
      significantly increased in diabetic retinopathy in comparison with non-diabetic
      controls and diabetic subjects with no retinopathy. This has implications for
      controlling hypertension and hyperglycaemia as a strategy in reducing morbidity
      from diabetic retinopathy.

PMID- 1393113
TI  - How safe is Scottish hot air?

PMID- 1393112
TI  - Social class differences in infant mortality in Sweden: comparison with England
      and Wales.
AB  - OBJECTIVES: To investigate social class differences in infant mortality in Sweden
      in the mid-1980s and to compare their magnitude with that of those found in
      England and Wales. DESIGN: Analysis of risk of infant death by social class in
      aggregated routine data for the mid-1980s, which included the linkage of Swedish
      births to the 1985 census. SETTING: Sweden and England and Wales. SUBJECTS: All
      live births in Sweden (1985-6) and England and Wales (1983-5) and corresponding
      infant deaths were analysed. The Swedish data were coded to the British registrar
      general's social class schema. MAIN OUTCOME MEASURES: Risk of death in the
      neonatal and postneonatal period. RESULTS: Taking the non-manual classes as the
      reference group, in the neonatal period in Sweden the manual social classes had a
      relative risk for mortality of 1.20 (95% confidence interval 1.02 to 1.43) and
      those not classified into a social class a relative risk of 1.08 (0.88 to 1.33).
      In the postneonatal period the equivalent relative risks were 1.38 (1.08 to 1.77)
      for manual classes and 2.14 (1.65 to 2.79) for the residual; these are similar to
      those for England and Wales (1.43 (1.36 to 1.51) for manual classes, 2.62 (2.45
      to 2.81) for the residual). CONCLUSIONS: The existence of an equitable health
      care system and a strong social welfare policy in Sweden has not eliminated
      inequalities in post-neonatal mortality. Furthermore, the very low risk of infant
      death in the Swedish non-manual group (4.8/1000 live births) represents a target
      towards which public health interventions should aim. If this rate prevailed in
      England and Wales, 63% of postneonatal deaths would be avoided.

PMID- 1393114
TI  - Controlling deaths from volatile substance abuse in under 18s: the effects of
      legislation.

PMID- 1393115
TI  - Captopril associated lacrimation and rhinorrhoea.

PMID- 1393116
TI  - Cortical blindness after nifedipine treatment.

PMID- 1393117
TI  - Sexual dysfunction after gemfibrozil.

PMID- 1393118
TI  - Ventricular asystole and overdose with atenolol.

PMID- 1393119
TI  - Changes in drug treatment after discharge from hospital in geriatric patients.
AB  - OBJECTIVES: To ascertain changes in drug treatment of elderly patients after
      discharge from hospital and to identify areas of communication which may require
      improvement. DESIGN: Follow up of patients six to 14 days after discharge, when
      the drugs supplied by the hospital should have run out and a further supply
      obtained from the general practitioner. Patients were also asked about
      information supplied to them by health care professionals during their hospital
      stay. SUBJECTS: 50 elderly patients discharged from five geriatric wards (mean
      age 76.9 years). SETTING: Sunderland District Health Authority. MAIN OUTCOME
      MEASURE: Drugs taken after discharge from hospital. RESULTS: After returning home
      the drug regimen of 45 patients differed from that prescribed on discharge from
      hospital, with 11 patients taking a different dose, 10 having stopped drugs, and
      20 taking new drugs. Possible influencing factors included an incomplete drug
      history, the continuation of drugs taken before hospital admission, and changes
      in the prescription not attributable to a conscious clinical decision. Lack of
      information also contributed; 46 patients could not recall being told when to
      take drugs before discharge. CONCLUSION: Closer communication is needed between
      hospital and community health care professionals to ensure that patients are
      informed about their discharge prescription and continuation of treatment.

PMID- 1393120
TI  - AIDS, ethics, and clinical trials. Institute of Medical Ethics Working Party on
      the Ethical Implications of AIDS.

PMID- 1393121
TI  - ABC of colorectal diseases. Faecal incontinence.

PMID- 1393122
TI  - Containing the costs of Medicare.

PMID- 1393123
TI  - Intramuscular vitamin K and childhood cancer.

PMID- 1393124
TI  - Intramuscular vitamin K and childhood cancer.

PMID- 1393125
TI  - Intramuscular vitamin K and childhood cancer.

PMID- 1393126
TI  - Intramuscular vitamin K and childhood cancer.

PMID- 1393127
TI  - Vitamins face control worldwide.

PMID- 1393128
TI  - Vitamins face control worldwide.

PMID- 1393129
TI  - Vitamins face control worldwide.

PMID- 1393130
TI  - Vitamins face control worldwide.

PMID- 1393131
TI  - Oestrogen replacement after oophorectomy.

PMID- 1393132
TI  - Oestrogen replacement therapy after oophorectomy.

PMID- 1393133
TI  - Oestrogen replacement after oophorectomy.

PMID- 1393134
TI  - Midwifery and body fluid contamination.

PMID- 1393135
TI  - Midwifery and body fluid contamination.

PMID- 1393136
TI  - Medical reports for courts.

PMID- 1393137
TI  - Medical reports for courts.

PMID- 1393138
TI  - Paternal occupations of children with leukemia.

PMID- 1393139
TI  - Paternal occupations of children with leukemia.

PMID- 1393140
TI  - Classifying suicide.

PMID- 1393141
TI  - Classifying suicide.

PMID- 1393142
TI  - Monitoring ambulatory blood pressure in general practice.

PMID- 1393143
TI  - Frequency of citation and outcome of cholesterol lowering trials.

PMID- 1393144
TI  - Health care for elderly in Japan.

PMID- 1393145
TI  - The death penalty.

PMID- 1393146
TI  - The death penalty.

PMID- 1393148
TI  - Cyclin B is associated with centrosomes in Drosophila mitotic cells.
AB  - We have studied by way of confocal laser scanning microscopy the subcellular
      localization of cyclin B in Drosophila-cultured cells and report here evidence
      that a part of the cyclin B cell pool is closely associated with the centrosome.
      This cyclin B centrosomal signal is strong in prophase and metaphase but
      disappears during anaphase. Moreover, the signal is absent in the acentriolar
      Drosophila cell line 1182-4. These results put forward additional arguments
      suggesting that the centrosome plays an important role in the control of the cell
      cycle.

PMID- 1393147
TI  - Pain during mammography.

PMID- 1393149
TI  - Interaction of the Golgi membranes isolated from rabbit liver with microtubules
      in vitro.
AB  - We have developed a reconstituted model system to study the interaction of the
      Golgi membranes isolated from rabbit liver with taxol-stabilized bovine-brain
      microtubules without microtubule-associated proteins (MAPs). The Golgi membranes
      are associated with microtubules. The sheets of vesicles and the membranous
      tubules are observed along microtubules by direct visualization using
      differential-interference-contrast, dark field, or fluorescence microscopy. The
      monoclonal antibody against Golgi membranes suggests that the Golgi membranes,
      but not the contaminating vesicles, are interacting with microtubules. The degree
      of association is assayed quantitatively using rhodamine-labeled microtubules
      after separation of the complex from unbound microtubules by centrifugation upon
      sucrose gradient. The association is inhibited by crude MAPs, purified MAP2, or
      1.0 mM ATP. However, the association neither requires the cytosol from rat liver
      or bovine brain nor N-ethylmaleimide, brefeldin A, or GTP-gamma-S. The
      association is mediated by trypsin-sensitive peripheral protein(s) on the Golgi
      membranes.

PMID- 1393150
TI  - Alterations in erythrocyte membrane fluidity in children with trisomy 21: a
      fluorescence study.
AB  - Membrane fluidity of erythrocytes obtained from 15 children with trisomy 21 and
      20 healthy controls were studied by measuring steady-state fluorescence
      anisotropy and fluorescence lifetime of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1
      (4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) incorporated in
      hemoglobin-free erythrocyte membranes. Our results demonstrate a significant
      decrease in DPH fluorescence anisotropy and a significant increase in TMA-DPH
      fluorescence anistropy in erythrocytes from subjects with trisomy 21. No
      significant differences between the two groups were observed in the fluorescence
      lifetime of DPH and TMA-DPH. These data suggest an increase in membrane fluidity
      in the interior part of the membrane and a decrease in fluidity at the lipid
      water interface region. This could be in part attributed to an increased
      oxidative damage in trisomy 21.

PMID- 1393151
TI  - The calcium loading of secretory granules. A possible key event in stimulus
      secretion coupling.
AB  - The review focuses on calcium accumulation by secretory organelles. The
      observation that secretory granules contain variable and often important
      quantities of calcium (1-200 mM of total calcium) can be interpreted as a
      maturation index. A progressive loading with calcium would be permitted by a
      Ca2(+)-transport mechanism on the granular membrane and calcium-binding molecules
      in the granular core. The saturation of this store by the stimulus-induced
      calcium transient would permit in mature (calcium-loaded) granules the ionic
      crisis leading to exocytosis. The inside of secretory organelles being acidic,
      calcium influx into the granule can be driven by calcium-proton exchange. The
      calcium-proton exchanger could be a Ca2(+)-ATPase.

PMID- 1393152
TI  - Probe-tube microphone measurements with very young infants.
AB  - The practicalities of performing probe-tube microphone measurements in a clinical
      environment with unsedated infants were examined. External ear resonance curves
      (unaided response) were obtained for both ears of a group of infants aged 0-6
      months and an adult comparison group. A repeat measure (with probe-tube
      repositioning) was made to estimate the test-retest reliability of these
      measures. Results showed that the mean infant resonance frequency (4200 Hz)
      occurred at a significantly (P less than 0.005) higher frequency than the mean
      adult resonance frequency (2950 Hz). Infants test-retest differences for
      resonance frequency (mean = 286 Hz, s.d. = 404 Hz) and size of peak (mean = 2.2
      dB, s.d. = 2.6 dB) showed acceptable stability for the measurements. Size of
      resonance peak was found to vary positively with ear canal volume; however,
      estimation of ear canal volume from tympanometry did not provide a useful
      indicator of the size of the peak. The probe-microphone measurements were found
      to be feasible, repeatable and practical with these infants.

PMID- 1393153
TI  - Acoustical changes of loudly spoken speech and their effects on speech
      recognition in hearing-impaired listeners.
AB  - The level of speech is usually increased in conversations with unaided hearing
      impaired listeners. However, the speaker may talk at conversational levels to
      aided hearing-impaired persons. In this case, the level of speech is
      electronically increased by the hearing aid. In the present study, the acoustical
      changes of loudly spoken speech and their effects on speech recognition were
      investigated in 20 patients with sensorineural hearing loss. Eight test words of
      the German Speech Intelligibility Test ('Freiburger Sprachtest') were recorded at
      original levels of 60 and 75 dB SPL by a male speaker. Both recordings were
      presented to hearing-impaired subjects at a playback level of 75 dB SPL. Thus,
      the level of the 60 dB SPL recording was increased electronically by 15 dB. For
      the 75 dB SPL recording, playback and recording levels were identical. The
      average whole-word score was 49% for the 60 dB SPL recording and 39% for the 75
      dB SPL recording. This difference was statistically significant (0.002 less than
      P less than 0.005). The results of the speech recognition ability tests could be
      explained by the acoustical changes of the loudly spoken speech. In the 75 dB SPL
      recording, the levels of voiceless fricatives, nasals and plosives were
      significantly lower than in the 60 dB SPL recording. Spectrally, the fundamental
      frequency was increased and the configuration of the first formant was altered in
      the 75 dB SPL recording. The significance of the findings for clinical speech
      audiometry and hearing aid evaluation is discussed.

PMID- 1393154
TI  - Acoustic evaluation of earmoulds in situ: a comparison of impression and earmould
      materials.
AB  - Laboratory research has been carried out on the accuracy of both ear impression
      and earmould materials. The present work was undertaken to assess such materials
      in vivo. An objective clinical method of earmould evaluation was developed, based
      on estimation of the attenuation in the acoustic feedback path. The method was
      used to assess the acoustic performance of earmoulds made from three earmould
      materials of different texture, when prepared from two different impression
      materials. It was shown that the choice of impression material made a significant
      difference to earmould performance. For greatest accuracy, addition cured
      silicone impression materials are recommended.

PMID- 1393155
TI  - Tactiling: a usable support system for speechreading?
AB  - The purpose of this study was to find out whether deafened adults can take
      advantage of the extra information in speechreading given by the vibrational and
      motional patterns picked up by placing a hand on a speaker's throat and shoulder,
      and how valuable this tactile supplement is as a support system for
      speechreading. We have named this method--speechreading with tactile supplement-
      tactiling. Eight deafened adults participated in the study, conducted with a pre
      test/post-test control group design. The experimental and the control groups took
      speechreading classes together. The experimental group received additional
      individual training in tactiling during six 1 h lessons. Both the experimental
      and the control groups were tested, before and after training, first by a
      familiar person and thereafter by an unfamiliar person. The results demonstrated
      two significant main effects. Tactiling is generally better than speechreading
      alone, and the results from the test given by the familiar speaker are better
      than with the unfamiliar speaker. The main effect of tactiling indicates that the
      method is worth pursuing as a communication system for the deafened adults.
      Possible reasons for the direct effect of tactiling are discussed, as well as
      modifications of this 'natural' device.

PMID- 1393156
TI  - Early intervention in schizophrenia: theoretical background and clinical
      strategies.
AB  - Clinical observation and retrospective studies have provided considerable
      information as to the nature of decompensation into acute schizophrenic illness.
      These themes have been further developed in studies designed to reduce overall
      exposure to neuroleptics whilst maintaining adequate prophylaxis against relapse.
      This review extracts from the literature information which could be harnessed to
      prevent, abort or ameliorate florid schizophrenic relapse. Emphasis is laid upon
      the coordination of psychological and medical approaches, describing in some
      detail both the theoretical background and practical intervention strategies in
      development, and exploring their implications for the role of clinical
      psychologists.

PMID- 1393157
TI  - Treatment of depressive and obsessive-compulsive symptoms in OCD by imipramine
      and behaviour therapy.
AB  - The efficacy of behavioural treatment of obsessive-compulsive disorder (OCD) has
      been well documented. However, severely depressed OCD patients showed fewer short
      and long-term benefits than less depressed patients. The present study tested
      the hypothesis that reduction of depression by imipramine prior to behaviour
      therapy would enhance the effects of behavioural therapy on depressed OC
      patients. Thirty-eight patients were divided into highly and mildly depressed
      groups according to their scores on the Beck Depression Inventory; half of each
      group received imipramine and half received placebo for six weeks. All patients
      then received three weeks of daily behavioural treatment (exposure and response
      prevention) followed by 12 weekly sessions of supportive psychotherapy. Results
      indicated that although imipramine improved depressive symptoms in depressed
      patients, it did not affect OC symptoms. Behaviour therapy markedly reduced OC
      symptoms but, contrary to our hypothesis, imipramine did not potentiate the
      effects of behaviour therapy. No differences between highly depressed and mildly
      depressed patients on OC symptoms were found in their responses to behavioural or
      supportive therapy.

PMID- 1393158
TI  - Sense of coherence, self-esteem, depression and hopelessness as correlates of
      reattempting suicide.
AB  - Sense of coherence (SOC) has been proposed as a psychological factor that
      predicts good health and positive adjustment. The three components of SOC:
      manageability, comprehensibility and meaning were assessed together with
      depression, hopelessness and self-esteem as factors predicting future suicidal
      ideation and behaviour in parasuicides. One hundred and fifty hospitalized
      parasuicides were evaluated on these measures and followed up after six months to
      determine their current level of suicidal ideation and whether they had been
      readmitted for a further attempt or killed themselves in the intervening period.
      Suicidal ideation on admission was best predicted by a low score on the SOC
      meaning subscale and also significantly related to the other predictor variables.
      Suicidal ideation at the six-month follow-up was best predicted by the SOC
      subscales manageability and comprehensibility. These two SOC subscales also
      emerged as discriminators of suicidal behaviour over the six months following
      admission. Overall prediction of suicidal behaviour was enhanced by also
      including the background variables of age, a history of previous attempts,
      unemployment and whether the attempter was living alone. The study ends with a
      discussion of the importance of widening the focus when assessing and predicting
      suicidal risk to include not only predictions based on pathology but also
      psychological factors that promote adjustment.

PMID- 1393159
TI  - The development of a six-item short-form of the state scale of the Spielberger
      State-Trait Anxiety Inventory (STAI).
AB  - Two studies are reported describing the development of a short-form of the state
      scale of the Spielberger State-Trait Anxiety Inventory (STAI) for use in
      circumstances where the full-form is inappropriate. Using item-remainder
      correlations, the most highly correlated anxiety-present and anxiety-absent items
      were combined, and correlated with scores obtained using the full-form of the
      STAI. Correlation coefficients greater than .90 were obtained using four and six
      items from the STAI. Acceptable reliability and validity were obtained using six
      items. The use of this six-item short-form produced scores similar to those
      obtained using the full-form. This was so for several groups of subjects
      manifesting a range of anxiety levels. This short-form of the STAI is therefore
      sensitive to fluctuations in state anxiety. When compared with the full-form of
      the STAI, the six-item version offers a briefer and just as acceptable scale for
      subjects while maintaining results that are comparable to those obtained using
      the full-form of the STAI.

PMID- 1393160
TI  - Inhibition through negative priming with Stroop stimuli in schizophrenia.
AB  - Stroop stimuli were used to measure the negative priming effect in eight positive
      and 10 negative schizophrenics, 21 depressive and 35 healthy control subjects in
      order to test hypotheses of insufficient versus persistent cognitive inhibition
      in schizophrenia. Data show that schizophrenics do not increase their response
      times to suppressor Stroop items compared to identical but neutral Stroop stimuli
      because the insufficiency of their inhibitory processes weakens the distractor
      suppression effect. However, pre-exposure of the lexical distractor can
      compensate for insufficient inhibitory mechanisms in positive but not negative
      schizophrenics, suggesting more severe deterioration in the latter. Depressed
      subjects showed a slower development of cognitive inhibition. The results suggest
      important differences in the temporal evolution of inhibitory processes, and are
      discussed in terms of Hemsley's (1977) and Frith's (1979) theories.

PMID- 1393161
TI  - Verbal fluency: a NART-based equation for the estimation of premorbid
      performance.
AB  - A sample of 142 subjects free of neurological or psychiatric disorder were
      administered the National Adult Reading Test (NART) and a verbal fluency (VF)
      test. A highly significant correlation between the NART and VF was obtained
      indicating that premorbid ability should be taken into account when interpreting
      VF performance. A regression equation was built to estimate premorbid performance
      on VF from the NART. A highly significant difference between predicted and
      obtained VF was obtained in a sample of neurological patients (N = 38). For ease
      of use, a table converting NART errors to predicted VF scores is presented.

PMID- 1393162
TI  - Predictors of outcome in the treatment of bulimia nervosa.
AB  - Outcome predictors of a cognitive behavioural group treatment for bulimia nervosa
      were examined. Pre-treatment self-esteem, binge frequency and ineffectiveness,
      but not duration of disorder, significantly predicted outcome on at least one
      measure (binge frequency or overall eating pathology) at post-treatment and/or
      three-month follow-up. The results are related to previous studies and to
      theories of maintenance of the disorder.

PMID- 1393163
TI  - Subscales of the Dysfunctional Attitude Scale.
AB  - Eight subscales based on items drawn from the original 100-item Dysfunctional
      Attitude Scale (Weissman & Beck, 1978) were developed as potential markers of
      specific cognitive vulnerabilities (Beck, 1987). Six of the eight subscales were
      correlated with both depression and anxiety symptom measures, indicating that the
      'vulnerabilities' represented by these subscales are unlikely to be specific to
      depression.

PMID- 1393164
TI  - Factor structure of the Wechsler Adult Intelligence Scale-revised (WAIS-R): a
      clinical sample.
AB  - Factor analysis was performed on a heterogeneous clinical sample of neurological
      patients. Both a two- and a three-factor model were extracted. The two-factor
      solution corresponded to Wechsler's categorization of verbal and performance
      subtests. The three-factor solution suggested a verbal comprehension factor, a
      perceptual organization and a third factor with highest loadings on digit span,
      arithmetic and digit symbol. Both models were consistent with factor models
      obtained from the standardization sample. As has previously been reported in
      neurologically impaired samples, the third factor was relatively more prominent
      than in the standardization sample. This study provides further evidence for the
      robustness of the WAIS-R factor structure across different populations and gives
      good support for the use of the WAIS-R in British clinical samples.

PMID- 1393165
TI  - Representations of health, illness and medicines: coping strategies and health
      promoting behaviour.
AB  - This study focuses on the different representations of health, illness and
      medicines that are held by the population of the Basque Country. In addition,
      relationships between these representations and both coping strategies towards
      first symptoms of disease and health-promoting actions were studied. Three
      different representations were found: (a) an active/'against medicines'
      representation; (b) a 'magical/pro-medicines' representation; and (c) a
      representation that combines aspects of the previous representations. These
      representations were anchored in different social groups (defined by age,
      educational background, etc.) and were related to different coping strategies in
      the event of first symptoms of illness, and to differences in health-promoting
      behaviour.

PMID- 1393166
TI  - Exhaustion as precursor of cardiac death.
AB  - Excess fatigue is the most prevalent precursor of sudden cardiac death. This
      state may reflect prolonged tension or heart disease. In order to test the first
      explanation a prospective study was done among 3365 males, aged 45-59 years. This
      cohort was followed during an average period of 9.5 years. Exhaustion was
      assessed by the statement: 'At the end of the day I am completely exhausted
      mentally and physically'. Among those free of coronary heart disease at the
      beginning, 69 subjects died because of myocardial infarction. Data were analysed
      using Cox's regression analysis. The results showed a highly significant
      interaction between duration of follow-up and exhaustion upon the risk of cardiac
      death. The hazard ratios for exhaustion were 8.96, 6.33, 4.47 and 3.16 for the
      first 10, 20, 30 and 40 months of follow-up respectively. Thereafter the
      association between exhaustion and cardiac death is no more significant. It is
      argued that exhaustion before cardiac death does not reflect manifest heart
      disease but that an interaction between prolonged tension and subclinical levels
      of ischaemia may increase the risk of cardiac death.

PMID- 1393167
TI  - Information giving in oncology: a preliminary study of tape-recorder use.
AB  - This paper describes a pilot study of information giving in an oncology setting.
      This was achieved by randomly allocating patients to having their consultation
      tape-recorded or not. The results suggest that this approach increases the
      retention of information in patients as well as reducing their levels of anxiety.
      The method is cheap and easy to use, acceptable to patients and their families,
      and does not inhibit the consultation process.

PMID- 1393168
TI  - Monitoring, medical fears and physical symptoms.
AB  - In this study it was found that subjects with a high monitoring coping style had
      higher scores on the blood injury scale of the Fear Questionnaire and reported
      more physical symptoms on the Pennebaker Inventory of Limbic Languidness than
      those with a low monitoring style. Implications of these findings are briefly
      discussed.

PMID- 1393169
TI  - Selective processing of eating, weight and shape related words in patients with
      eating disorders and dieters.
AB  - The Stroop colour-naming task was used to investigate selective processing of
      eating, weight and shape related words in two groups of dieters, patients with
      anorexia nervosa, patients with bulimia nervosa and a group of non-dieting
      controls. 'Normal dieters' were not different from the non-dieting controls.
      Dieters with a history of features of an eating disorder but no diagnosis and the
      patients with anorexia nervosa, like the patients with bulimia nervosa, showed
      selective processing of information related to eating, weight and shape.

PMID- 1393170
TI  - Pre-operative anxiety variables as possible predictors of post-operative stay in
      hospital.
AB  - The extent to which measures of pre-operative anxiety predict post-operative
      hospital stay, over and above what is predicted by biographical, medical status
      and post-operative anxiety variables, was examined in 81 cholecystectomy
      patients. Hierarchical multiple regression analysis revealed that patients who
      were older, had lower health status and suffered from wound infection, had a
      longer post-operative hospital stay than others. None of the pre-operative
      anxiety measures had a significant incremental value in the prediction of the
      post-operative hospital stay.

PMID- 1393171
TI  - Financial compensation and head injury.

PMID- 1393174
TI  - Evaluating sensory regulation as a method to improve awareness in patients with
      altered states of consciousness: a pilot study.
AB  - The status of sensory stimulation as a clinical procedure is still in some doubt.
      Recent papers have shown no significant clinical changes as a result of sensory
      intervention but this may be due to an inappropriate model on which these
      procedures were based. This paper outlines the results of a controlled pilot
      study, based on a sensory regulation model currently being tested at the Casa
      Colina Peninsula Rehabilitation Center, Los Angeles. The study contrasts the
      outcome of four patients treated in a sensory regulated environment with four who
      were exposed to sensory stimulation of an unregulated kind. The results are quite
      encouraging in favour of a sensory regulation approach.

PMID- 1393172
TI  - Intercorrelation of lesions detected by magnetic resonance imaging after closed
      head injury.
AB  - Forty-three patients with closed head injuries were followed up 5 to 12 months
      post-injury. Patients had magnetic resonance imaging (MRI) and performed a
      variety of neuropsychological tests. There were systematic relationships between
      lesions in different sites: depth of lesions in orbito-frontal regions, frontal
      regions, and temporal poles were particularly strongly intercorrelated. Depth of
      lesions in specific sites also correlated with an overall measure of brain
      damage: the number of areas with lesions present. After correcting for premorbid
      differences there were significant correlations between lesions in specific sites
      and scores on three out of five WAIS subtests. Scores on these three subtests
      also correlated significantly with overall brain damage. In general, hemispheric
      sites which were significantly related to neuropsychological measures also showed
      significant intercorrelations among themselves. The findings stress the
      importance of patterns of lesions in head injury, and emphasize the difficulty of
      showing differential localization of cerebral function in this population.

PMID- 1393173
TI  - Compensation neurosis rides again.
AB  - Compensation neurosis (CN), also known as accident neurosis, has generally not
      been considered to be a 'real' disorder. In 1961 it was seemingly laid to rest by
      Henry Miller, a distinguished neurologist, in a sharp article which appeared in
      the British Medical Journal. Miller's view of patients who presented
      psychological symptoms following accidents or traumas was suspicious. Compensated
      or not, his view seemed to be that they should have their legal process finished
      as quickly as possible and then they will miraculously convalescence. Miller's
      work, it appeared, was the coup de grace for this ill-defined diagnosis. Today,
      however, compensation neurosis seems to ride again. After a prolonged silence in
      the psychiatric literature, new papers are emerging, strongly suggesting that
      this vanishing diagnosis be reconsidered. This new trend will be presented.

PMID- 1393175
TI  - Effects of intensity of treatment and length of stay on rehabilitation outcomes.
AB  - The combined effects of intensity of treatment and length of stay during
      inpatient rehabilitation hospitalization on the outcomes of 95 traumatic brain
      injury patients were examined. Outcome was assessed using the Rancho Scale and
      three measures of functional status--physical performance, higher-level cognitive
      skills, and cognitively mediated physical skills. The effects of intensity of
      treatment and length of stay were assessed using 2 x 2 analyses of variance with
      repeated measures. The results showed clearly that both length of stay and
      intensity of treatment affect outcomes. Patients in the long length of stay group
      consistently made more progress across all outcome variables than patients in the
      short length of stay group. However, the greater progress of the long length of
      stay patients was from a point significantly more disabled than that of the short
      length of stay patients, with improvement at discharge to the point at which the
      groups were now equal. The effect of intensity of treatment was significant or
      closely approached significance for higher-level cognitive skills and Rancho
      Level. In the long length of stay group, the two intensity groups were initially
      equivalent, but at discharge the high-intensity group surpassed the low-intensity
      group. The practical implications of the results are discussed.

PMID- 1393176
TI  - The effectiveness of directed multisensory stimulation versus non-directed
      stimulation in comatose CHI patients: pilot study of a single subject design.
AB  - In view of the difficulties in finding control groups in sensory stimulation
      research, a single case methodology was explored. A pilot study was conducted on
      six comatose CHI patients in a neurosurgical intensive care unit. Each patient
      was given alternating weeks of directed multisensory stimulation (SDS) and non
      directed stimulation (NDS) for half an hour a day in an ABAB single subject
      design. Eye movement, motor and vocal response to stimulation were recorded using
      the Sensory Stimulation Assessment Measure (Rader Scale). Comparisons of eye
      movement and motor responses on the Rader Scale appeared to indicate a greater
      degree of responsiveness to the SDS as compared with the NDS treatment. Overall
      improvement levels on the GCS, Rancho Scale and Western Neurosensory Stimulation
      Profile are discussed. The results are interpreted as indicative of the potential
      value of using single case methodology in this population, and future research
      directions are also discussed.

PMID- 1393177
TI  - Functional outcome of low-level traumatically brain-injured admitted to an acute
      rehabilitation programme.
AB  - A retrospective analysis of functional status at discharge, disposition, Glasgow
      Outcome Scale (GOS) score at 6 months and 1 year was undertaken for 23
      consecutive 'low-level' traumatic brain injury victims admitted in a state of
      complete dependency to an acute rehabilitation programme. All patients met
      criteria for extremely severe traumatic brain injury, with an average Glasgow
      Coma Scale score of 8.7 at admission to the rehabilitation facility (an average
      of 44 days post-injury). All but three patients made significant functional gains
      during the acute rehabilitation stay. Almost half of the study patients (48%)
      were discharged at home while the rest went to sub-acute rehabilitation
      programmes. At 6 months post-injury eight (35%) met GOS criteria for 'good'
      outcome or 'moderate disability'. A review of clinical features, categories of
      functional progress, and relationships of outcome and disposition to variables
      known to have predictive value in such a patient population is described.
      Analysis of variables related to admission selection criteria that have been used
      in this rehabilitation programme is presented and the basis and implications of
      selection criteria discussed.

PMID- 1393178
TI  - Differential effects of spinal cord injury and head injury on marital adjustment.
AB  - Central nervous system (CNS) trauma can produce a multitude of physical and
      psychological sequelae, depending on the neurological level of injury. Clinicians
      have long recognized the adjustment difficulties posed in marriages of CNS trauma
      victims, yet there is little research documentation for this observation. The
      marital relationships of moderate (n = 31) and severe (n = 17) head injury (HI)
      groups and a spinal cord injury (SCI) group (n = 24) were assessed through
      spouses' self-reports in interview and through standardized questionnaires.
      Analyses indicated that the three groups were not statistically different in age,
      number of months post-injury, pre- and post-injury occupational status, and level
      of income. In the post-injury marital relationship, the severe HI group was
      significantly lower than the moderate HI and SCI groups on standardized and
      validated scales assessing affectional expression (p less than 0.002), dyadic
      satisfaction (p less than 0.001), dyadic cohesion (p less than 0.01), and total
      dyadic adjustment (p less than 0.001). On a scale of social role functioning, the
      severe HI group's performance was significantly lower than the moderate HI and
      SCI groups (p less than 0.005). These results empirically substantiate the
      clinical observation that adjustment difficulties may be more intense for wives
      of the severely head injured than the moderately injured or the SCI, as they must
      deal with neuropsychological as well as physical fall-out from the injury.

PMID- 1393179
TI  - Delusional reduplication following closed-head injury.
AB  - Somatic delusions following brain injury are not uncommon, and have been well
      documented in the literature. This study documents a case of somatic delusion
      which was seen in a patient following a head injury secondary to a motorcycle
      accident. Although perhaps not typical it serves to illustrate an interesting
      example of a somatic delusion following head trauma. On recovery from coma this
      patient reported the existence of a 'third arm' adjacent to the limb that had
      received the greatest impact in the accident. The patient was unreceptive to any
      counter-persuasions and in fact remained largely unconcerned about this addition
      to his anatomy. A thorough neuropsychological evaluation was carried out in an
      attempt to seek an explanation for this phenomenon. The results suggest that the
      phenomenon has at least a partly psychiatric aetiology rather than a purely
      neurological foundation.

PMID- 1393180
TI  - Minor and severe head injury emotional sequelae.

PMID- 1393181
TI  - Neuropsychiatric correlates of theta bursts in patients with closed head injury.

PMID- 1393182
TI  - Post-traumatic and emotional symptoms in different subgroups of patients with
      mild head injury.
AB  - Post-concussional symptoms, such as headache, dizziness and irritability, are
      thought to result from the emotional stress associated with decreased cognitive
      performance after a head injury. A questionnaire-based investigation was carried
      out in 71 patients with mild head injury (MHI), using a heterogeneous item pool
      in order to study the interrelationships between traditional post-concussive
      complaints, cognitive problems, and more emotional and functional complaints.
      Factor analysis indicated that post-concussive symptoms loaded together with
      items on problems associated with decreased work performance and fatigability on
      a first factor, whereas psychovegetative and emotional complaints loaded together
      on a second factor. Two rating scales were constructed from the relevant items
      and were used to compare between subgroups of MHI patients and non-concussed
      controls. Patients with uncomplicated MHI had significantly higher scores than
      non-concussed subjects on the post-concussive-cognitive scale, but not on the
      emotional-vegetative scale. Patients with multiple head injuries or pre-existing
      emotional problems had higher scores on both the post-concussive-cognitive scale
      and the emotional-vegetative scale than MHI patients without a history of
      emotional problems. Reliable rating scales may be useful in multidiagnostic
      studies of MHI patients.

PMID- 1393183
TI  - Prediction of motor status 3 and 6 months post severe traumatic brain injury: a
      preliminary study.
AB  - The prediction of outcome following severe traumatic brain injury has received
      considerable attention in recent years. Previous prediction studies have focused
      on a long-term follow-up or prediction period. The reported outcome measures
      generally adopted a global approach (e.g. independent living) in terms of the
      prediction of physical function. The objective of the present study was to
      construct clinically useful predictive equations of motor system status, as
      represented by selected postural reactions (indicators of central nervous system
      function). Specifically, these equations would serve to predict the recovery of
      equilibrium and protective reactions both at 3 and 6 months post-injury,
      respectively. A stepwise multiple logistic regression analysis was performed,
      where nine predictive variables were considered using a multivariate approach.
      The results indicate that coma duration followed by age contribute significantly
      to the predictive capability of the models at both 3 and 6 months post-injury.
      Specifically, at 3 months, the predictive variables 'coma duration' and 'age'
      enabled an 84.62% correct prediction rate, whereas, at 6 months, 'coma duration'
      and 'age' enabled a 79.49% correct prediction rate. In addition, the exact
      probabilities (for given sample ages and coma durations) and associated 95%
      confidence intervals were calculated based on the predictive models obtained. The
      theoretical framework underlying these predictive models can form the basis for
      further studies. Furthermore, these preliminary predictive models have potential
      implications for early treatment planning and patient management.

PMID- 1393184
TI  - Neuropsychiatric correlates of theta bursts in patients with closed head injury.
AB  - Twenty-five head-injured patients with localized theta bursts on standard or 24 h
      ambulatory EEG were administered a standardized interview for neuropsychiatric
      symptoms associated with complex partial seizures (e.g. olfactory hallucinations,
      memory gaps) and a battery of neuropsychological tests. Although the formal
      neuropsychological test performances of these patients were relatively normal
      they reported an abundance of seizure-like behavioural symptoms. While the
      frequency of these symptoms was high, they did not occur in a stereotyped complex
      or sequence. These findings suggest that localized theta bursts may be diagnostic
      of an underlying neuroelectrical disorder.

PMID- 1393185
TI  - Event-related potential measurement of deficits in information processing
      following moderate to severe closed head injury.
AB  - Event-related potentials may offer more precision than behavioural measures for
      understanding the extent and timing of information processing difficulties that
      follow closed head injury (CHI). Behavioural tests consistently indicate a
      general reduction in cognitive function but lack adequate diagnostic or
      prognostic function. This study compares a group of seven CHI patients, in which
      time since injury varied between 1 and 5 years following injury, with 10 matched
      controls on a three-tone discrimination task. Abnormality in the processing of
      tones as early as 200 ms following their onset, as measured by the P2 and N2
      components of the event-related potential, indicated a general difficulty with
      tone discrimination. This abnormality was obtained despite differing damage
      profiles over patients and is likely to be due to the diffuse aspects of damage
      normal in CHI. These results also indicate that functional deficits in CHI
      patients can extend up to 5 years or more. A correlation between P2/N2 amplitudes
      and time since injury, however, suggests that both these components normalize
      with the passage of time and offers the prospect of a sensitive, non-behavioural
      measure of recovery in cognitive processing.

PMID- 1393186
TI  - Antimicrobial prophylaxis for fractured base of skull in children.
AB  - The details are reviewed of 50 children who were treated over a 10-year period
      with clinical signs of fractured base of skull. Two patients died early without
      signs of sepsis--due to the severity of their head injuries. Of the remainder, 23
      received antibiotic prophylaxis and 25 did not. One patient from each of these
      groups developed pneumococcal meningitis, and they were successfully treated. Our
      results correlate well with those previously published, confirming the low
      incidence of infective complications with or without prophylaxis. The need to
      assemble a large enough series to make statistically significant conclusions
      regarding this infrequent condition is highlighted throughout the literature,
      which is reviewed here.

PMID- 1393187
TI  - Remediation of alexia without agraphia: a case study.
AB  - Following a left temporoparietal-occipital haemorrhage and surgery, a 43-year
      old, right-handed male exhibited alexia without agraphia. A remediation programme
      consisted of training in head turning to compensate for a right visual field
      defect, letter-by-letter reading aloud and covertly, drill with flash-cards to
      improve word recognition and practice in naming objects to improve dysnomia. The
      patient's reading improved markedly over a 6-week period and he was able to
      resume work as a respiratory therapy supervisor. A post-morbid depression
      resolved concomitantly with the patient's return to work. The training programme
      and the patient's post-training approach to reading are discussed in terms of
      hemispheric functioning as well as 'direct path' and 'indirect path' reading. The
      effectiveness of training is considered in the context of spontaneous recovery.

PMID- 1393188
TI  - Brain injury rehabilitation: the need to bridge paradigms.

PMID- 1393189
TI  - Asymmetrical brain modulation of the immune response.
AB  - It is now well known that the central nervous system can regulate the immune
      system. Interestingly the two sides of the brain have been demonstrated to be
      differently involved in the modulation of immune responses. In rodents, lesions
      of right or left neocortex induced opposite effects on various immune parameters
      including mitogen-induced lymphoproliferation, interleukin-2 production,
      macrophage activation or natural killer cell activity. Furthermore in humans,
      left-handedness has been reported to be associated with a high incidence of
      immune disorders. Likewise in mice, the direction of a lateralized motor
      behavior, i.e., paw preference in a food reaching task, correlated with an
      asymmetrical pattern of brain organization, was shown to be associated with
      lymphocyte reactivity, natural killer cell activity and auto-antibody production.
      Conversely the immune system could send to the brain information that may be
      asymmetrically expressed. The experimental models for investigating asymmetrical
      brain modulation of the immune system may be useful for studying physiological,
      pathological and genetic aspects of neuroimmunomodulation.

PMID- 1393191
TI  - Cholera's lesson: the need to invest in health.

PMID- 1393190
TI  - Neuroendocrine regulatory mechanisms in the choroid plexus-cerebrospinal fluid
      system.
AB  - The CSF is often regarded as merely a mechanical support for the brain, as well
      as an unspecific sink for waste products from the CNS. New methodology in
      receptor autoradiography, immunohistochemistry and molecular biology has revealed
      the presence of many different neuroendocrine substances or their corresponding
      receptors in the main CSF-forming structure, the choroid plexus. Both older
      research on the sympathetic nerves and recent studies of peptide
      neurotransmitters in the choroid plexus support a neurogenic regulation of
      choroid plexus CSF production and other transport functions. Among the endocrine
      substances present in blood and CSF, 5-HT, ANP, vasopressin and the IGFs have
      high receptor concentrations in the choroid plexus and have been shown to
      influence choroid plexus function. Finally, the choroid plexus produces the
      growth factor IGF-II and a number of transport proteins, most importantly
      transthyretin, that might regulate hormone transport from blood to brain. These
      studies suggest that the choroid plexus-CSF system could constitute an important
      pathway for neuroendocrine signalling in the brain, although clearcut evidence
      for such a role is still largely lacking.

PMID- 1393192
TI  - First documented outbreak of dengue in the Peruvian Amazon region.
AB  - This article describes a classical dengue outbreak caused by dengue serotypes 1
      and 4 that occurred from March to July 1990 in the city of Iquitos and
      surrounding areas of Loreto Department in the Peruvian Amazon. Epidemiologic data
      indicate that more than 150,000 persons may have been affected in Iquitos alone.
      Another dengue outbreak occurred in Tarapoto, a city in the neighboring
      department of San Martin. Laboratory data indicate that the same dengue serotypes
      were involved in both outbreaks. No cases of dengue hemorrhagic fever/shock
      syndrome appear to have occurred. Prior to this outbreak, no indigenous dengue
      cases had been documented in Peru.

PMID- 1393194
TI  - Schistosoma mansoni cercaria and schistosomulum antigens in serodiagnosis of
      schistosomiasis.
AB  - Schistosoma mansoni cercaria and schistosomulum obtained in vitro were used in
      immunofluorescence (IF) tests and indirect hemagglutination (IHA) tests of 137
      study sera, 44 from subjects infected with S. mansoni and 93 from healthy
      subjects residing outside areas endemic for the disease. The results of these
      tests were compared with those obtained by testing the same sera using
      conventional adult worm antigen, and also with the initial clinical and
      parasitologic diagnoses of the 137 subjects providing the study sera. Regarding
      sera from acute versus chronic cases, IF testing of the acute sera consistently
      detected IgA antibodies along with IgM and IgG, the last two being found
      consistently in chronic sera. Also, the geometric mean of the IgM antibody titers
      found in the IF tests was higher for acute than for chronic sera. Excluding IF
      IgA, which was negative for chronic cases, the sensitivity of the other types of
      tests (IF IgG, IF IgM, and IHA) using cercaria and schistosomulum antigens, both
      under evaluation, ranged from 0.773 to 0.955, the specificity ranged from 0.957
      to 1.000, the efficiency ranged from 0.927 to 0.985, the predictive value of
      positives ranged from 0.909 to 1.000, and the predictive value of negatives
      ranged from 0.903 to 0.979. No statistical differences were observed between
      these results and those obtained with conventional adult worm antigen. This
      suggests that cercaria and schistosomulum antigens, both of which can be produced
      more quickly and cheaply than adult worm antigen, could serve as reliable
      alternatives to adult worm antigen in the serodiagnosis of schistosomiasis
      mansoni.

PMID- 1393195
TI  - Prevalences of tuberculosis and other respiratory diseases among people over age
      15 in the northeast sector of Medellin, Colombia.
AB  - A survey was conducted in 1988 to estimate the prevalence of respiratory symptoms
      and pulmonary tuberculosis in people over age 15 in the Northeast Sector of
      Medellin, Colombia, an area suffering from severe socioeconomic depression. A
      cluster sample was selected for this purpose and 3,731 adults were interviewed in
      their homes. Those classified as respiratory symptomatics (ones reporting a cough
      lasting two weeks or more) were asked to provide samples for three sputum-smear
      examinations. The prevalence of pulmonary tuberculosis found in this survey was
      2.68 cases per 1,000 subjects, a rate substantially greater than the prevalence
      of tuberculosis cases recorded in the Northeast Sector, and the prevalence of
      respiratory symptomatics was 70 per 1,000 subjects. Of eight subjects whose cases
      had been diagnosed previously, three said they had abandoned treatment. The
      prevalence of respiratory symptomatics was higher among poorly educated subjects
      and among those sleeping in poorly ventilated and/or overcrowded quarters.
      Overall, the survey data suggest that the tuberculosis control program in
      Northeast Medellin confronts a spectrum of problems ranging from low case
      detection rates and high rates of abandoned treatment to social conditions and
      behavior patterns that foster host vulnerability and disease transmission.

PMID- 1393193
TI  - An AIDS-related knowledge, attitudes, beliefs, and practices survey among
      schoolchildren in Barbados.
AB  - A knowledge, attitudes, beliefs, and practices (KABP) survey was performed among
      Barbadian secondary schoolchildren 11-16 years old in January 1990. The survey
      sought to assess the children's knowledge of AIDS and human immunodeficiency
      virus (HIV) transmission; their attitudes toward people with HIV/AIDS; their
      sexual practices; and changes needed in education programs seeking to reduce
      childhood HIV transmission. A pretested self-administered questionnaire was used.
      The survey sample was derived by selecting every eleventh student on the rosters
      of all the secondary schools in Barbados. All of the survey respondents completed
      the questionnaire on the same day, having been assembled examination-style for
      that purpose. The results showed high levels of correct knowledge about the
      principal routes of HIV transmission. However, a considerable proportion of the
      respondents harbored incorrect beliefs regarding mosquito transmission and
      dangers to blood donors, and many showed uncertainty or incorrect knowledge
      regarding possible HIV transmission by biting, spitting, or use of public
      toilets. About a third of the children (51.4% of the boys and 18.7% of the girls)
      said they had experienced sexual intercourse, though only 20% reported being
      sexually active in the year preceding the survey. Three-quarters of the sexually
      experienced group said they knew how to use condoms, but only a third said there
      was any time when they had used protection during sexual intercourse. Overall,
      the results indicate that education efforts prior to the survey had been
      effective, but that reinforcement of such efforts as well as their extension into
      the primary schools is warranted. Further research directed at helping these
      efforts to encourage more meaningful changes in sexual behavior is also needed.

PMID- 1393197
TI  - What is a clinical engineer? Issues in definition.

PMID- 1393196
TI  - Research in the Argentine outback: the health quest of Salvador Mazza.

PMID- 1393199
TI  - An evaluation of environment and climate control in seven infant incubators.

PMID- 1393198
TI  - Military clinical engineering: the Israel Defense Forces experience.

PMID- 1393200
TI  - Capacitive coupled stray currents during laparoscopic and endoscopic
      electrosurgical procedures.
AB  - Capacitively coupled currents may not be appreciated during laparoscopic and
      endoscopic radiofrequency electrosurgery. Two specific problems are documented
      and quantified: coupling of current into metal trocar cannulas during
      laparoscopic surgery and coupling of current into a guide wire during endoscopic
      surgery. The examples can yield power levels in excess of 25 watts (laparoscopic)
      and 15 watts (endoscopic) on nearby metal conductors, which can in turn be
      dissipated into patient organs such as the bowel or the common bile duct. This
      capacitive coupling can be, in part, responsible for serious patient
      complications. Methods to minimize capacitive coupling, e.g., active electrode
      shielding, dispersive metal cannulas, sheathed guide wires, and bipolar active
      electrodes, are discussed for each example.

PMID- 1393201
TI  - Real-time display of flow-pressure-volume loops.
AB  - Graphic display of respiratory waveforms can be valuable for monitoring the
      progress of ventilated patients. A system has been developed that can display
      flow-pressure-volume loops as derived from a patient's respiratory circuit in
      real time. It can also display, store, print, and retrieve ventilatory waveforms.
      Five loops can be displayed at once: current, previous, reference, "ideal," and
      previously saved. Two components, the data-display device (DDD) and the data
      collection device (DCD), comprise the system. An IBM 286/386 computer with a
      graphics card (VGA) and bidirectional parallel port is used for the DDD; an eight
      bit microprocessor card and an A/D convertor card make up the DCD. A real-time
      multitasking operating system was written to control the DDD, while the DCD
      operates from in-line assembly code. The DCD samples the pressure and flow
      sensors at 100 Hz and looks for a complete flow waveform pattern based on flow
      slope. These waveforms are then passed to the DDD via the mutual parallel port.
      Within the DDD a process integrates the flow to create a volume signal and
      performs a multilinear regression on the pressure, flow, and volume data to
      calculate the elastance, resistance, pressure offset, and coefficient of
      determination. Elastance, resistance, and offset are used to calculate Pr and Pc
      where: Pr[k] = P[k]-offset-(elastance.V[k]) and Pc[k] = P[k]-offset
      (resistance.F[k]). Volume vs. Pc and flow vs. Pr can be displayed in real time.
      Patient data from previous clinical tests were loaded into the device to verify
      the software calculations. An analog waveform generator was used to simulate flow
      and pressure waveforms that validated the system.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1393202
TI  - Automated testing of arrhythmia monitors using annotated databases.
AB  - Arrhythmia-algorithm performance is typically tested using the AHA and MIT/BIH
      databases. The tools for this test are simulation software programs. While these
      simulations provide rapid results, they neglect hardware and software effects in
      the monitor. To provide a more accurate measure of performance in the actual
      monitor, a system has been developed for automated arrhythmia testing. The
      testing system incorporates an IBM-compatible personal computer, a digital-to
      analog converter, an RS232 board, a patient-simulator interface to the monitor,
      and a multi-tasking software package for data conversion and communication with
      the monitor. This system "plays" patient data files into the monitor and saves
      beat classifications in detection files. Tests were performed using the MIT/BIH
      and AHA databases. Statistics were generated by comparing the detection files
      with the annotation files. These statistics were marginally different from those
      that resulted from the simulation. Differences were then examined. As expected,
      the differences were related to monitor hardware effects.

PMID- 1393203
TI  - The Takeda Model UA-751 blood pressure and pulse rate monitor.
AB  - The performance of the Takeda Model UA-751 oscillometric blood pressure and pulse
      rate monitor was compared with readings taken using auscultatory technique and
      the mercury manometer. Significant correlations (p less than 0.0001) were found
      between the clinical standard and the UA-751 on measurements of systolic (r =
      0.85) and diastolic (r = 0.77) blood pressure. Comparison of the pulse rate
      measurements obtained using the Grass Polygraph with those of the UA-751 resulted
      in a reliable correlation (r = 0.98; p less than 0.0001), as well. The results
      provide empirical support for the validity of the UA-751 under controlled
      laboratory conditions. However, the results suggest heightened error in the
      measurement of systolic pressure when the UA-751 is used by individuals who have
      high blood pressures.

PMID- 1393204
TI  - Dynamic image-adaptive x-ray beam limiters.
AB  - The imaging capability of the dynamic spatial reconstructor (DSR), a fast
      (60/second), synchronous, multislice (up to 240) computed x-ray tomography
      scanner, has been limited by the suboptimal match of the dynamic range of the x
      ray projection images with that of the image-intensified charge-coupled device
      (CCD) video sensors. Effective blockage of the "raw" beam component of the
      projection images by fixed shutters is generally impossible because of the rapid
      change in the multiple angles of view that result from the 15 RPM rotation of the
      scanner assembly about the object of study. For this reason a programmable,
      dynamic, image-adaptive x-ray beam shutter system has been developed to reduce
      the "raw" beam component of the x-ray image without degrading the image in the
      region of interest. This system is designed to dynamically position 28 shutters
      (two for each of 14 x-ray sources) continuously and independently, as a function
      of the angle of view, so as to selectively obscure any unattenuated "raw" x-ray
      beam passing alongside the object of study at all angles of view for each x-ray
      source.

PMID- 1393205
TI  - Recommendations for specifications and operator interface design for new medical
      infusion pumps.

PMID- 1393206
TI  - The clinical engineer as medical laser safety officer.

PMID- 1393207
TI  - Improving biomedical engineering documentation skills: a case study.

PMID- 1393208
TI  - The quest for better validation: a critical comparison of the AAMI and BHS
      validation protocols for ambulatory blood pressure measurement systems.
AB  - Two validation procedures are currently available for the evaluation of
      ambulatory blood pressure measurement systems--the standard of the Association
      for the Advancement of Medical Instrumentation (AAMI) and the protocol of the
      British Hypertension Society (BHS). Both are in the process of revision. Four
      systems for measuring 24-hour ambulatory blood pressure--SpaceLabs 90207, Novacor
      DIASYS 200, Del Mar Avionics Pressurometer IV, and Takeda TM-2420--were evaluated
      according to the BHS protocol, which incorporates many of the features of the
      AAMI standard, under similar conditions by the same personnel and in the same
      subjects, so as to examine the relative merits of the two evaluation procedures.
      Three recorders of each model were subjected to a before-use inter-device
      variability test, followed by an in-use phase and an after-use inter-device
      variability test. The main validation test was carried out in 86 subjects with a
      wide range of pressures, the results being analyzed according to the BHS grading
      system and the AAMI validation criteria. The SpaceLabs 90207 and the DIASYS 200
      achieved B and C grades, respectively, according to the BHS protocol and also
      satisfied the AAMI criteria for accuracy. The Pressurometer IV achieved a Grade C
      rating for systolic pressure and a Grade D rating for diastolic pressure and the
      Takeda TM-2420 achieved Grade D ratings for both systolic pressure and diastolic
      pressure. Both these devices failed to fulfil the AAMI criteria for accuracy and
      both failed to function in the main validation test and had to be
      replaced.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393209
TI  - The measurement of radiant temperature in neonatal thermal environments.
AB  - Heat exchange through radiation is recognized as the dominant mode of heat
      transfer for an infant nursed in an incubator or warmer. A radiometer was
      constructed to measure the planar radiant temperature experienced by the infant.
      Two heat-flow sensors of different emissivities were mounted onto a heat sink
      such that one measured principally convective heat exchange while the other
      measured convective and radiant heat exchange. The radiant heat exchange was
      obtained from the difference between these values, from which the planar radiant
      temperature could be calculated. The spatial variation in planar radiant
      temperatures within an incubator and warmer was determined by orienting the
      instrument towards the five orthogonal hemispheres sensed by the infant abdomen,
      sides, head, and feet. In the incubator, the spatial variation in radiant
      temperatures exceeded 2 degrees C, or four times the spatial variation in air
      temperatures (0.5 degrees C). The radiant warmer had a spatial variation of 18
      degrees C in radiant temperature at three-fourths of maximum power, corresponding
      to a variation in heat flux over the infant's surface of 100 W/m2. This thermal
      asymmetry would be expected to influence the variation in surface skin
      temperature, and thus the thermal stimuli to the infant thermoregulatory system.
      Further research is needed to understand the clinical significance of this
      asymmetry. Furthermore, the precise control over air temperature in modern
      incubators provides a false sense of thermal control and stability. Radiant
      temperature needs to be measured in addition to air temperature if the thermal
      performances of incubators and warmers are to be fully understood.

PMID- 1393210
TI  - A system for in-vitro characterization of heart valve bioprostheses under
      accelerated fatigue conditions and under physiologic conditions.
AB  - An accelerated fatigue testing system and a pulse duplicator (heart simulator)
      were used in a set-up in which pressure differences and pulsatile flow rates
      across prosthetic heart valves, as well as machine rates, could be measured using
      a real-time on-line data-acquisition system. With this information available, an
      immediate in-vitro characterization of the fluid dynamics of prosthetic heart
      valves could be obtained under both physiologic and accelerated conditions. In
      addition to the fatigue tester and the pulse duplicator, a signal conditioner, a
      DC amplifier, an analog-to-digital converter, and a digital microcomputer
      comprised the essential hardware. For the purpose of this study, special
      acquisition software was developed. By means of the same computational
      algorithms, all quantitative fluid dynamics data could be calculated using
      information from both the pulse duplicator and the fatigue tester, so that direct
      comparisons and correlations could be approached. Pressure difference-flow rate
      relationships for the two machines were comparable.

PMID- 1393212
TI  - Oestrogens and depression in women.

PMID- 1393211
TI  - Thermal profiles of electrocauteries, the Nd:YAG laser, and the electromagnetic
      field focusing system.
AB  - Electromagnetic-field focusing (EFF) is a method of converging induced eddy
      current onto a pointed tip of a tuned length return circuit in the near field of
      a resonator, which results in the production of high temperature. Previously
      reported applications of this method include various devices for local
      hyperthermia and a precision surgical device. The latter is currently being used
      in human clinical trials under two investigational device exemptions from the
      Food and Drug Administration. In the present work, the thermal profile produced
      in a uniform, tissue-simulating phantom by the hand-held probe of the surgical
      EFF system is compared with those produced by mono- and bipolar electrocauteries
      and by a contact Nd:YAG laser. At the equivalent power setting and 2-cm insertion
      depth, the EFF probe was shown to have a tighter thermal profile than the
      monopolar electrocautery or the contact Nd:YAG laser. This finding is consistent
      with earlier histologic evidence that brain cortical tissue cut by the surgical
      EFF probe had minimal thermal damage in the tissue surrounding the incision.

PMID- 1393213
TI  - Negligence: case for the defence.

PMID- 1393214
TI  - Improving the preregistration period.

PMID- 1393215
TI  - Physiological consequences of complete cardiac denervation.
AB  - The transplanted human heart remains functionally denervated for 5 or more years
      postoperatively. Denervation has a number of implications for cardiac function,
      not the least of which is the inability of transplant recipients to experience
      ischaemic pain. The study of the denervated heart has not only shed light on the
      physiology of cardiac transplantation but also provided further insights into the
      functioning of the normally innervated heart.

PMID- 1393216
TI  - Current treatment of ulcerative colitis.
AB  - Ulcerative colitis is a chronic relapsing disease which may become manifest
      either early or late in life. This article examines current drug treatment
      strategies and considers possible therapeutic options for the future.

PMID- 1393217
TI  - Haematological and immunological abnormalities in eating disorders.
AB  - Eating disorders are associated with a wide range of physical symptoms and signs
      and with aberrant laboratory findings. The frequency of haematological and
      immunological abnormalities reflects the key role of adequate nutrition in the
      maintenance of normal bone marrow and immune function. The nature of these
      abnormalities and their clinical implications are discussed here.

PMID- 1393218
TI  - Boring arteries: television and tubes, a new peripheral vascular surgery?
AB  - Modern methods of recanalizing occluded peripheral blood vessels essentially
      began with various endarterectomy techniques. However, apart from carotid
      endarterectomy, none has made a lasting impact, mainly due to poor long-term
      patency.

PMID- 1393219
TI  - Emergency caesarean section.

PMID- 1393220
TI  - Seasonal affective disorders.
AB  - The recurrent nature of mania and depression has led to a search for factors that
      might predict the timing of episodes. There has recently been a resurgence of
      interest in the possibility that seasonal changes may precipitate affective
      illness.

PMID- 1393221
TI  - Inhaled anaesthetic agents: from halothane to the present day.
AB  - Despite the enormous resources spent on research and development, only two new
      volatile agents have been introduced into anaesthetic practice in the UK since
      the introduction of halothane. This article reviews their properties and looks
      towards changes in volatile anaesthetic availability in the near future.

PMID- 1393222
TI  - Clinical exams: interviewing in front of examiners.
AB  - The re-examination of a patient in front of two examiners is a major part of the
      clinical exams in psychiatry. However, for the candidate it is the most anxiety
      provoking part of the exam, and possibly the area of greatest weakness.

PMID- 1393223
TI  - Cannon balls.
AB  - Radiological terminology includes a number of interesting and often amusing terms
      intended to help us understand and remember the pathological abnormality being
      described. What radiological sign is illustrated in Fig. 1 and what is the
      differential diagnosis?

PMID- 1393224
TI  - HRT: Non-compliance and education.

PMID- 1393226
TI  - Science as sin.

PMID- 1393225
TI  - Opt-outs trust to luck.

PMID- 1393227
TI  - Effects of digoxin.

PMID- 1393228
TI  - Management of patients with airway obstruction.

PMID- 1393229
TI  - Cardiomyoplasty for heart failure.

PMID- 1393230
TI  - Blood donor screening: benefits and costs.

PMID- 1393231
TI  - Terminology and learning disability.

PMID- 1393232
TI  - Management of acute myeloid leukaemia.
AB  - Advances in the management of acute myeloid leukaemia have led to an improvement
      in survival from what was invariably a fatal disease. This review presents some
      of these advances and outlines the modern management of this condition.

PMID- 1393233
TI  - Rheumatology and the gut.
AB  - Some conditions may present with gastrointestinal and rheumatological
      manifestations. Salmonella osteomyelitis results from direct infection of bone
      following gut infection and bacteraemia, but in other conditions the pathogenesis
      is less clear. There may be a microbial cause for rheumatoid arthritis; however,
      this theory remains unproven.

PMID- 1393234
TI  - Monitoring of cerebral function.
AB  - The cerebral function of sedated ventilated patients cannot be assessed by
      neurological examination, yet many of these patients may have changing cerebral
      function which needs urgent treatment. Many methods of measuring cerebral
      function are available and are reviewed in this article along with
      recommendations for practical monitoring within the intensive care unit.

PMID- 1393235
TI  - A guide to lung function tests.
AB  - In patients with respiratory disease, measurement of lung function should be part
      of the assessment if possible. In the ward, clinic and lung function laboratory
      there are tests available to examine airflow, lung volume, gas transfer and
      exercise capacity. These provide information on lung function which may be vital
      for adequate diagnosis and assessment of the patient.

PMID- 1393237
TI  - Doctors' liability for prebirth injury.

PMID- 1393236
TI  - Heterosexual transmission of human immunodeficiency virus.
AB  - Heterosexual human immunodeficiency virus (HIV) transmission accounts for most
      cases of HIV infection and acquired immunodeficiency syndrome worldwide.
      Moreover, in the developed world the proportion of individuals infected
      heterosexually is rising faster than the proportion infected by other routes,
      with an increase in the number of women infected. Defining the factors associated
      with heterosexual transmission may help control new infections.

PMID- 1393238
TI  - Guide to postgraduate exams: how to prepare.
AB  - Ways in which doctors might learn, revise and prepare for postgraduate exams are
      outlined in this article. Some educational principles are described to explain
      why understanding is far more useful and permanent than rote-learning.
      Suggestions are also made about exam technique.

PMID- 1393239
TI  - High-flyers in medicine.

PMID- 1393241
TI  - Ultrasonographic assessment of osteoporosis.

PMID- 1393240
TI  - Obtaining venous access in a fitting patient.

PMID- 1393242
TI  - Who should undergo carotid endarterectomy?

PMID- 1393243
TI  - Ten-digit and nine-digit replantation (4 cases).
AB  - Ten or nine-digit amputation is a very rare injury. From March, 1987 to June,
      1988, we replanted two cases of ten-digit complete amputation and two cases of
      nine-digit complete amputation with success. The maximum ischaemic time was 39 h
      and the operation time was between 25 and 31 h. All digits survived completely
      except for partial necrosis of one finger. The follow-up has been 13-20 months,
      and all the patients have a pair of good, functional and aesthetically acceptable
      hands.

PMID- 1393244
TI  - Tissue expanded free flaps.
AB  - Over the last few years there have been various reports of the use of tissue
      expanders as an adjunct to microvascular free transfer of tissue. This study
      looks at the effect of expanding the actual flap prior to transfer. Two case
      reports are given and it is proposed that expanded free flaps are large and thin.
      They have a capsule which enables them to be safely sutured under tension. They
      are "delayed" by the expansion process and the donor deformity is minimal. It is
      suggested that tissue expansion is a useful technique prior to free flap transfer
      for the reconstruction of large defects.

PMID- 1393245
TI  - Thromboembolic prophylaxis in plastic surgery: an appraisal.
AB  - A survey by questionnaire was conducted amongst consultant plastic surgeons in
      the UK: 54 replies were received (44% response rate). Three consultants (5.5%)
      never used any form of DVT prophylaxis. The other 51 (94%) used some form of
      prophylaxis in at-risk patients. The methods used were found to be diverse. Ten
      respondents belonged to units with fixed policies for prophylaxis. A controlled
      trial is suggested to provide statistical evidence of the need for thromboembolic
      prophylaxis among plastic surgical patients. We believe there is a need for units
      to develop fixed protocols for the prevention of thromboembolism in at-risk
      patients.

PMID- 1393246
TI  - A computerised machine for the facilitated production of intermingled skin
      grafts.
AB  - The introduction of intermingled allograft/autograft skin grafting in western
      countries has long been hampered by high costs, due to the personnel requirements
      to produce this special form of graft. We have solved this problem by designing
      and constructing a computer-controlled machine, which in one operation punches
      holes out of strips of allogeneic donor skin and in another cuts fitting islets
      out of autogenous skin and transfers them into these holes. In comparison to
      manual preparation, this machine not only accelerates the production of
      intermingled skin grafts, but it also inserts the islets with superior accuracy,
      which is very important for the final functional and cosmetic result.

PMID- 1393247
TI  - The surgical management of dystrophic epidermolysis bullosa (excluding the hand).
AB  - Fifty patients with Dystrophic Epidermolysis Bullosa (DEB) underwent surgery
      including release of limb, oral, anal, eye and penile contractures and treatment
      of chronic skin ulceration or skin tumours. Correction of contractures involves
      extensive release of skin and underlying tissues, with split skin grafting of
      secondary defects. Specific regions are discussed. Recurrence is inevitable due
      to ongoing disease; however, functional improvement is obtained for several
      years. Management of chronic skin ulceration with split skin grafting has failed
      to produce long term healing, with local flaps successful but limited by the
      problem of donor site instability. Nine of the 17 patients over 20 years of age
      developed squamous cell carcinomas (29 lesions), benign hyperkeratosis (9) or
      malignant melanoma (1) requiring excision and skin grafting or amputation of
      digits. Local recurrence was infrequent (3 squamous cell carcinomas), with
      distant metastatic spread occurring in 1 patient.

PMID- 1393248
TI  - A versatile method for reconstruction of finger defects: reverse digital artery
      flap.
AB  - Four types of the reverse digital artery flap--standard, extended, and innervated
      standard and extended--were developed for 52 finger defects. The arising pattern
      of the dorsal branch which was included in the innervated flap was studied and
      classified in cadaver dissections. Topographically, the described "Lai's line" is
      a useful guide to locate the underlying digital artery. Refinements in flap
      design and surgical technique resulted in favourable functional and cosmetic
      results. The average two-point discrimination of the reconstructed fingertip was
      6.8 mm and 3.9 mm in the noninnervated and innervated flaps, respectively. This
      versatile flap is an ideal and reliable option for one-stage reconstruction of
      various finger defects.

PMID- 1393249
TI  - Medial Langenbeck: experience of a modified Von Langenbeck repair of the cleft
      palate. A preliminary report.
AB  - Early experience of a modified Von Langenbeck repair of cleft palate is reported.
      In each case the traditional method of repair has been adopted, but with the
      relieving incision placed medial to the greater palatine artery. Out of a total
      of 40 patients over a 2-year period 8 were noted to have a fistula, of which 4
      closed spontaneously, leaving 4 (10%) potentially requiring further surgery. The
      modified oral layer closure was conceived with muscle repair directed at
      restoring normal anatomy and concentrating on construction of a median dorsal
      convexity.

PMID- 1393250
TI  - Morbidity after gold weight insertion into the upper eyelid in facial palsy.
AB  - Morbidity and outcome after gold weight insertion into the upper eyelid in
      patients with lagophthalmos were assessed retrospectively by patient
      questionnaire and case-note review. Results indicated that although satisfaction
      with the lid and overall facial appearance was high, complications and symptoms
      attributable to the gold weights were not uncommon.

PMID- 1393251
TI  - The relationship between prostaglandin E1 applied area and flap survival rate.
AB  - Using a silicone gel sheet continuous drug delivery system containing
      Prostaglandin E1 (PGE1), the relationship between flap survival rate and the site
      of drug application was studied. Skin flaps measuring 2 x 9 cm were raised on the
      dorsum of rats, and divided into 3 areas. Area 1 was within 3 cm of the flap tip,
      area 2 was between 3-6 cm from the flap tip including the critical zone, and area
      3 was the portion within 4 cm of the flap base. Further, area 4 was a strip of
      skin around the flap, 1 cm in width. Compared to the control group, a significant
      increase in flap survival rate was seen only when PGE1 was administered to area 2
      (p < 0.01, t-test). Specimens injected with dye intravascularly showed an
      increase in the number of thick vessels in area 3, when PGE1 was applied only to
      area 3. However, when PGE1 was applied to area 2, there was no significant
      vascular increase in area 3. Instead, an extensive network of fine vessels was
      observed in area 2.

PMID- 1393252
TI  - Pneumosinus dilatans as the aetiology of progressive bilateral blindness.
AB  - Pneumosinus Dilatans is a rare condition of the craniofacial skeleton which was
      diagnosed in an adolescent male who presented with progressive bilateral
      blindness and many features of osteodysplasty (Melnick-Needles Syndrome). The
      clinical course and unusual pathology of this case which included the compression
      of both optic nerves within long tubes of bone are described, together with the
      surgical intervention performed to arrest the patient's loss of vision.

PMID- 1393253
TI  - A vascularised periosteal flap: anatomical study.
AB  - Twenty-seven anatomical studies were done to elucidate the periosteal blood
      supply on the lateral surface of the shaft of the tibia. The dissection of a
      vascularised periosteal flap is described. The applications of this flap are
      discussed in the light of previous clinical and experimental reports on
      periosteal flaps and a successful clinical case is detailed. This flap has
      application for electively treating bony non union. It may also be used as a free
      flap in an acute trauma situation involving bone loss.

PMID- 1393254
TI  - Transcutaneous extravasation of silicone following breast augmentation.
AB  - Transcutaneous leakage of silicone in the absence of sinus formation has not
      previously been described. We present a case in which silicone extravasation
      occurred following the rupture of a breast implant inserted 14 years previously.

PMID- 1393255
TI  - Necrotising fasciitis in the head and neck region.
AB  - Necrotising fasciitis is an uncommon entity in present day medicine. Our review
      of the literature did not reveal any case involving the head and neck region. A
      case of this rare disease involving the head and neck region is presented.

PMID- 1393257
TI  - Medial gastrocnemius flap.

PMID- 1393256
TI  - Syringe suction drain.
AB  - A mini suction drain made up of a 20 cc glass syringe, a stainless steel spring
      and a scalp vein cannula (whose needle end has been cut off and multiple holes
      made in the distal 2.5-5 cm) is described. It is very useful in preventing
      postoperative haematoma formation, in nasogastric tube suction, in easy drawing
      up of fluids from vials, and in exploration of deep seated abscesses and
      collections. It is inexpensive, as syringe and spring can be re-used after
      sterilisation by autoclaving.

PMID- 1393258
TI  - Treatment of donor site defects.

PMID- 1393259
TI  - Evidence that the apparent complexity of receptor antagonism by angiotensin II
      analogues is due to a reversible and syntopic action.
AB  - 1. The interactions between angiotensin II (AII), two non-peptide antagonists DuP
      753 and IMI, and eight peptide analogues of AII were investigated on the rabbit
      isolated aorta assay. DuP 753 and IMI behaved as simple competitive antagonists
      (pKB values 8.4 and 6.8, respectively). To different degrees, all the AII-peptide
      analogue interactions failed to meet the basic criteria for simple competition.
      In addition to rightward shift, the most significant feature was a concentration
      dependent saturable depression of the upper asymptote of the AII concentration
      effect curves. 2. 'Washout' and combined dose-ratio analysis experiments, in
      which DuP 753 was used as a reference antagonist, indicated that the profile of
      peptide antagonism was solely due to a reversible and syntopic action at the AII
      receptor. 3. By use of an operational model of agonism (Black & Leff, 1983) as a
      starting point, it was possible to account for the data with a new model which
      describes reversible receptor occupancy and occupied receptor-determined,
      saturable reduction in the efficacy of AII. Model-fitting gave estimates of pKB
      values for the peptide analogues and agonist affinity and efficacy parameters for
      AII. 4. The model was successfully tested by applying it to qualitatively similar
      results obtained in a cross-tissue analysis on guinea-pig aorta, ileum and
      stomach. 5. A 'molecular' interpretation of the efficacy changes, based on the
      concepts of receptor internalisation and expression, is offered.

PMID- 1393260
TI  - Effect of the hypoglycaemic drug (-)-AZ-DF-265 on ATP-sensitive potassium
      channels in rat pancreatic beta-cells.
AB  - 1. It has previously been shown that the hypoglycaemic drug (-)-AZ-DF-265
      stimulates insulin release from mouse islets; in the presence of 3 mM glucose it
      also inhibits 86Rb-efflux from 86Rb-loaded islets. Based on these data we tested
      the hypothesis that (-)-AZ-DF-265 inhibits ATP-sensitive potassium channels. 2.
      We voltage-clamped the plasma membrane of single rat pancreatic beta-cells in the
      whole-cell configuration and measured the current flowing through ATP-sensitive
      potassium channels. (-)-AZ-DF-265 was applied to the outside of the cell; it
      inhibited the current half-maximally at a concentration of 1.2 +/- 0.2 nM with a
      Hill coefficient of 0.7 +/- 0.1. The inhibition was reversible on washing. 3. In
      intact RINm5F cells, the sulphonylurea [3H]-glibenclamide bound with an affinity
      of 0.24 +/- 0.01 nM and a Hill coefficient of 2.1 +/- 0.4. Treatment with (-)-AZ
      DF-265 led to the displacement of [3H]-glibenclamide; this effect was half
      maximal at 8.6 +/- 1.7 nM and displayed a Hill coefficient of 0.53 +/- 0.01.
      Meglitinide and tolbutamide, which represent, respectively, the benzamido and
      sulphonylurea moieties of glibenclamide, showed Hill coefficients of 0.8 +/- 0.1
      and 0.9 +/- 0.1, respectively. 4. At pH 7.4 and with phosphate/borate buffer, (-)
      AZ-DF-265 had an apparent octanol/water partition coefficient of about 53, which
      is intermediate between the partition coefficients of glibenclamide and
      glipizide. Nevertheless, (-)-AZ-DF-265 bound only to a minor degree to glass and
      plastic.5. In conclusion, (-)-AZ-DF-265 inhibits ATP-sensitive potassium channels
      and displaces [3H]-glibenclamide from the sulphonylurea receptor.

PMID- 1393261
TI  - Platelet activating factor and systemic anaphylaxis in Nippostrongylus
      brasiliensis-sensitized rats: differential effects of PAF antagonists.
AB  - 1. The effects of two platelet-activating factor (PAF) antagonists, WEB 2086 and
      BN 52021, in reducing the changes in extravasation (Evans blue technique) and
      blood flow (radiolabelled microsphere method) to various organs and tissues
      following anaphylactic shock in the Nippostrongylus brasiliensis-sensitized rat
      were investigated. 2. Both antagonists attenuated anaphylaxis-induced increases
      in plasma protein leak in the trachea, stomach and small intestine, although they
      did not block extravasation in the colon and kidneys. 3. Anaphylaxis-induced
      decreases in blood flow to the adrenals were effectively antagonized by WEB 2086,
      although this antagonist did not reverse blood flow decreases to any other
      tissues. BN 52021, on the other hand, did not alter anaphylaxis-induced decreases
      in blood flow to the adrenals, but effectively prevented dramatic decreases in
      blood flow to the large and small bowel and spleen. 4. Anaphylactic shock
      produced marked reduction in blood pressure that was partly reversed by WEB 2086,
      whereas BN 52021 effectively blocked the decreases in cardiac output. 5. Thus,
      PAF is responsible for some of the haemodynamic and extravasation of protein
      changes associated with systemic anaphylaxis in the rat, although the
      differential inhibition observed with the two antagonists suggests that PAF
      alters vascular responsiveness through different mechanisms in selected tissues.

PMID- 1393262
TI  - Functional comparisons of gastrin/cholecystokinin receptors in isolated
      preparations of gastric mucosa and ileum.
AB  - 1. The gastrin cholecystokinin (CCK) receptors mediating stimulation of acid
      secretion in rat isolated gastric mucosa (RGM) and contraction in guinea-pig
      isolated ileum longitudinal muscle-myenteric plexus (GPI) have been characterized
      by use of peptide agonists and the non-peptide antagonists, lorglumide,
      devazepide and L-365,260. 2. In RGM, gastrin peptides (sulphated gastrin
      heptadecapeptide (G-17), non-sulphated (ns) G-17 and pentagastrin) were potent
      agonists of acid secretion (EC50 values of 4.3, 16 and 27 nM respectively).
      Sulphated CCK octapeptide (CCK-8) was also a potent agonist, (EC50 = 0.9 nM), but
      was less efficacious, producing a lower maximal response. In contrast, in GPI,
      CCK-8 was a potent full agonist (EC50 = 1.4 nM) and was more than 1000 times more
      potent than the gastrin peptides in producing a sustained contractile response.
      3. In GPI, CCK-8 (0.1 to 100 nM) produced sustained contractile responses, whilst
      CCK-4 (3 to 1000 nM) produced transient responses. These responses had different
      sensitivities to atropine (1 microM), suggesting that more than one receptor may
      mediate contraction in this tissue. 4. In RGM, L-365,260 was the most potent
      antagonist of pentagastrin-stimulated acid secretion (pA2 = 7.6). This functional
      affinity estimate was similar to that for L-365,260 as an antagonist of
      excitatory responses in rat ventromedial hypothalamic slices (Kemp et al., 1989)
      but differed from binding affinity estimates in guinea-pig cortex and gastric
      glands (Freidinger, 1989). 5. In GPI, devazepide, L-365,260 and lorglumide
      yielded different affinity estimates when compared against CCK-8 and CCK-4 or
      pentagastrin respectively.These studies were consistent with the view that the
      sustained response produced by CCK-8 was mediated by CCKA receptors and the
      transient response produced by CCK-4 and pentagastrin was mediated by CCKB
      receptors.6. Affinity estimates for L-365,260 and lorglumide against CCK-4 or
      pentagastrin in GPI were significantly different from corresponding estimates
      against pentagastrin in RGM. These studies are consistent with the view that
      gastrin/CCKB receptors in GPI may differ from those in RGM.

PMID- 1393264
TI  - Effects of BRL 38227, sodium nitroprusside and verapamil on collateral perfusion
      following acute arterial occlusion in the rabbit isolated ear.
AB  - 1. We have used an isolated, buffer-perfused, rabbit ear model of acute arterial
      occlusion to investigate the effects of the nitrovasodilator sodium
      nitroprusside, the potassium channel activator BRL 38227 (the active (-)
      enantiomer of cromakalim) and the calcium antagonist, verapamil, on collateral
      perfusion in the absence of pharmacological tone. 2. Verapamil was the most
      potent vasodilator (EC50 = 72.6 +/- 32.0 nM) of 5-hydroxytryptamine/histamine
      induced tone in the rabbit isolated perfused ear. Sodium nitroprusside and BRL
      38227 were less potent with respective EC50 values of 488 +/- 75 nM and 296 +/-
      40 nM. Following inhibition of endothelium-derived relaxing factor (EDRF)
      synthesis, the potency of BRL 38227 was significantly (P less than 0.001)
      increased with an EC50 of 55.6 +/- 5.0 nM. 3. BRL 38227 at 500 nM and 3 microM
      induced substantial increases in collateral perfusion following arterial ligation
      in the absence of pharmacological tone compared to control. Furthermore 3 microM
      BRL 38227 completely reversed the attenuation of collateral perfusion which
      followed inhibition of EDRF synthesis with 100 microM NG-nitro-L-arginine methyl
      ester (L-NAME). 4. Sodium nitroprusside (500 nM and 3 microM) induced modest
      improvements in collateral perfusion in the early stages after arterial
      occlusion. 5. Verapamil did not influence collateral perfusion at either of the
      concentrations used (50 nM and 3 microM), even though it was a potent
      vasodilator. 6. The results of this study indicate that BRL 38227, and to a much
      lesser extent sodium nitroprusside, selectively improve collateral perfusion
      following arterial occlusion, even in the presence of effects of EDRF on acute
      collateralization, while verapamil has no effect. Furthermore, BRL 38227 also
      improves collateral perfusion following inhibition of EDRF synthesis. It remains
      to be established whether BRL 38227 has beneficial actions in acute arterial
      occlusion in vivo.

PMID- 1393263
TI  - Effect of MgATP on pinacidil-induced displacement of glibenclamide from the
      sulphonylurea receptor in a pancreatic beta-cell line and rat cerebral cortex.
AB  - 1. The effects of blockers and openers of K+ channels on binding of [3H]
      glibenclamide to microsomes obtained from a pancreatic beta-cell line (HIT-T15)
      or rat cerebral cortex were examined. 2. The blockers quinine, chlorpromazine and
      thiopentone and the openers cromakalim [(+/- ) 6-cyano-3,4-dihydro-2,2-dimethyl
      trans-4-(2-oxo-1- pyrrolidyl)-2H-benzo[b]pyran-3-ol] and minoxidil sulphate did
      not significantly interact with the sulphonylurea receptor of HIT-cells both at
      phosphorylating (presence of MgATP) and dephosphorylating (absence of MgATP)
      conditions. 3. In the absence of MgATP, pinacidil (200-500 microM) did not
      significantly displace [3H]-glibenclamide binding to microsomes from HIT-cells.
      The displacement of [3H]-glibenclamide binding was strongly enhanced by MgATP and
      was due to a decrease in the number of high affinity binding sites for
      glibenclamide. 4. MgATP enhanced pinacidil-induced inhibition of [3H]
      glibenclamide binding to microsomes from rat cerebral cortex. 5. The effect of
      MgATP on pinacidil-induced inhibition of [3H]-glibenclamide binding was
      maintained after solubilization of the membranes from HIT-cells or rat cerebral
      cortex. 6. It is concluded that the sulphonylurea receptor is regulated not only
      by sulphonylureas but also by the K+ channel openers, diazoxide and pinacidil,
      and by protein phosphorylation. The binding sites for sulphonylureas and these K+
      channel openers are not identical, but appear to be located at a single protein
      or at tightly associated proteins.

PMID- 1393266
TI  - Pituitary adenylate cyclase activating polypeptide is a potent vasodilator and
      oedema potentiator in rabbit skin in vivo.
AB  - 1. The effects of pituitary adenylate cyclase activating polypeptide (PACAP) on
      microvascular blood flow and plasma protein leakage were investigated in rabbit
      skin in vivo. 2. Intradermal injection of PACAP38, the 38 amino acid form of the
      peptide, caused a dose-dependent increase in blood flow measured by a 133Xe
      clearance technique. An equivalent increase in blood flow was induced by 10(-12)
      mol per site of PACAP38, 10(-12) mol per site of human alpha-calcitonin gene
      related peptide (CGRP) and 10(-10) mol per site of vasoactive intestinal
      polypeptide (VIP). 3. The vasodilator activity of PACAP38 was not significantly
      different from that of the 27 amino acid form of the peptide, PACAP27, when
      measured with a laser Doppler flow meter, causing a 104 +/- 14% compared with 110
      +/- 18% increase above basal blood flow at 10(-12) mol per site respectively. 4.
      At 10(-12) mol per site the effect of PACAP38 was longer lasting than that of
      CGRP. Blood flow remained significantly increased above control at 2 h with
      PACAP38 (P less than 0.05) whereas blood flow after intradermal CGRP had returned
      to control values by this time. 5. PACAP38 injected alone had no significant
      effect on microvascular leakage of 125I-labelled albumin. However, PACAP38
      significantly potentiated bradykinin-induced oedema where it was approximately
      100 fold more potent than VIP. 6. Oedema potentiation induced by PACAP38 was not
      inhibited by indomethacin at a dose which did inhibit potentiation of bradykinin
      induced oedema by arachidonic acid.7. PACAP38 is at least as potent as other
      peptides which have been postulated to be involved in the inflammatory response
      when tested in rabbit skin in vivo. PACAP may contribute to both the hyperaemia
      and oedema components of inflammation.

PMID- 1393265
TI  - Developmental changes in endothelium-dependent pulmonary vasodilatation in pigs.
AB  - 1. We compared in vitro endothelium-dependent vasorelaxant responses to
      acetylcholine (ACh) and the endothelium-independent vasodilator response to
      sodium nitroprusside (SNP) in prostaglandin F2 alpha (PGF2 alpha)-precontracted
      muscular pulmonary arteries (PA) from pigs aged 5 min to 2 h (neonatal), 3-10
      days, 3-8 weeks and adults. 2. In the pulmonary artery (PA) rings from neonatal
      animals, the vasodilator response to ACh was negligible. However, responses to
      ACh were present in all PA rings from older animals, being greatest at 3-10 days
      and then decreasing with age (P less than 0.001, ANOVA). ACh (30 microM) induced
      a 1 +/- 1%, 92 +/- 9%, 62 +/- 5% and 51 +/- 6% reduction of the PGF2 alpha
      generated tension in neonatal, 3-10 days, 3-8 weeks and adult groups,
      respectively. 3. The relaxant response to SNP was present in the PA rings from
      all age groups and increased with age (P less than 0.001, ANOVA). SNP (1 microM)
      induced relaxation was 55 +/- 9%, 73 +/- 7%, 97 +/- 5% and 93 +/- 6% in neonatal,
      3-10 days, 3-8 week and adult groups, respectively. 4. Removal of the vascular
      endothelium abolished the relaxant response to ACh but had no effect on the
      response to SNP in any groups. 5. NG-monomethyl-L-arginine (30 microM), a nitric
      oxide synthesis inhibitor, inhibited the response to ACh but not to SNP. The
      lipoxygenase inhibitor, nordihydroguaiaretic acid, had no significant effect on
      responses to ACh or SNP in any group.6. These findings suggest that the nitric
      oxide pathway may not play a part in dilating the pig pulmonary arteries at
      birth, but may be important during the transitional period of establishing a
      stable post-natal pulmonary circulation. The increase in response to SNP with age
      parallels the increase in smooth muscle cell myofilaments to which it may be
      related.

PMID- 1393267
TI  - Purinoceptors mediating relaxation and spasm in the rat gastric fundus.
AB  - 1. The relaxant and spasmogenic effects of purines and analogues were studied in
      longitudinal strips of rat gastric fundus to characterize the purinoceptors
      involved. Classification was studied by use of agonist potency orders and of
      antagonists in circumstances where the influence of confounding factors was
      reduced. In general tone was raised by carbachol (0.1 microM). 2. Adenosine
      produced relaxation and was potentiated by nitrobenzylthioinosine (NBTI, 0.3 and
      30 microM), an adenosine-uptake inhibitor. 8-Sulphophenyl-theophylline (8-SPT, 30
      microM), a selective P1-purinoceptor antagonist, antagonized adenosine and 5'-N
      ethylcarboxamidoadenosine (NECA), a selective agonist at P1-purinoceptors. 3. At
      resting tone, adenosine 5'-triphosphate (ATP) induced a small, phasic relaxation
      followed by a maintained spasm. When tone was raised by carbachol, ATP induced a
      larger relaxation followed by a smaller spasm. NBTI did not potentiate ATP, nor
      did 8-SPT antagonize ATP, suggesting that ATP does not act directly or indirectly
      at P1-purinoceptors. 4. With raised tone, and in the presence of indomethacin (10
      microM) and 8-SPT (30 microM), 2-methylthio ATP (2-MeSATP) and ATP produced
      relaxations followed by spasms while alpha,beta-methylene ATP (alpha,beta-MeATP)
      induced only relaxation; all responses were concentration-dependent. The
      compounds had similar slopes and maxima for relaxation and spasm. The rank orders
      of potency were 2-MeSATP much greater than alpha,beta-MeATP greater than ATP for
      relaxation and 2-MeSATP much greater than ATP for spasm.5. With raised tone, and
      in the presence of indomethacin and alpha 8-SPT, desensitization to alpha,beta
      MeATP (100microM) completely and only slightly suppressed responses to ATP and 2
      MeSATP, respectively, as relaxants but had no effect on relaxant responses to
      adenosine. The magnitude of the spasms to ATP and 2-MeSATP was considerably
      increased by desensitization with alpha,beta-MeATP but the spasm to KCl was not
      affected.6. With raised tone, and in the presence of indomethacin and 8-SPT,
      reactive blue 2 (10 AM) nonselectively antagonized ATP, 2-MeATP, a,P-MeATP,
      adenosine and isoprenaline as relaxants. Reactive blue 2 prevented the spasms to
      ATP and 2-MeSATP but not spasm to KC1.7. With raised tone, and in the presence of
      indomethacin, suramin (100 microM) antagonized ATP, but not adenosine, as
      relaxants and antagonized ATP, but not KC1, as spasmogens.8. It is proposed that
      adenosine is susceptible to nucleoside-specific uptake and acts predominantly via
      a P,-purinoceptor and also by a non-PI-purinoceptor mechanism. ATP- and
      alpha,beta-MeATP-induced relaxations probably occur via a P2x-purinoceptor. The
      anomalous nature of the 2-MeSATP-induced relaxation suggests it acts both via a
      P2x-purinoceptor and an additional mechanism. A P2y-purinoceptor is most likely
      to be involved in the spasms to ATP and 2-MeSATP. Therefore, the functional
      nature of the responses mediated by P2X- and P2y-purinoceptors, relaxation and
      spasm respectively, are opposite to those seen in most smooth muscles.

PMID- 1393268
TI  - Nitric oxide and relaxation of pig lower urinary tract.
AB  - 1. We studied the non-adrenergic, non-cholinergic (NANC) nerve-mediated
      relaxation induced by electrical stimulation in pig isolated lower urinary tract
      smooth muscle, and the possible involvement of the L-arginine (L-ARG)/nitric
      oxide (NO) pathway in this response. 2. Trigonal strips, precontracted by
      noradrenaline (NA), carbachol or endothelin-1 (ET-1), relaxed frequency
      dependently in response to electrical stimulation. Maximum relaxation was
      obtained at 6-8 Hz, and amounted to 56 +/- 2%, 77 +/- 3% and 62 +/- 6% of the
      agonist-induced tension in preparations contracted by NA, carbachol, or ET-1,
      respectively. Exposure to NG-nitro-L-arginine (L-NOARG; 10(-7)-10(-5) M)
      concentration-dependently reduced the relaxant response in preparations
      contracted by NA. L-NOARG (10(-6) M) reduced the maximal response to 51 +/- 8% of
      control. L-NOARG (10(-5) M) abolished all relaxation, and unmasked a contractile
      component; D-NOARG had no effect. Also in trigonal preparations, where the
      tension had been raised by carbachol or ET-1, L-NOARG (10(-5) M) markedly reduced
      relaxations evoked by electrical stimulation. 3. In trigonal preparations
      contracted by NA, maximal relaxation was increased after pretreatment with L-ARG
      (10(-3) M), and the inhibitory effect of L-NOARG (10(-6) M) was prevented.
      Incubation of the trigonal strips with methylene blue had no effect on
      relaxations elicited at frequencies less than 6 Hz, but a small inhibition was
      observed at higher frequencies. 4. Administration of NO (present in acidified
      solution of NaNO2) induced concentration-dependent relaxations in trigonal
      preparations contracted by NA, carbachol, or ET-1.L-NOARG (10-5 M) and L-ARG (10
      3M) had no effect on these relaxations. However, methylene blue (10-S M)
      significantly shifted the concentration-response curve for NO to the right. NANC
      relaxation and NO-induced relaxation of trigonal preparations were both inhibited
      by oxyhaemoglobin (10-5 M) and pyrogallol (10-4 M).5. In urethral preparations
      precontracted by NA, electrical stimulation caused frequency-dependent
      relaxations. A maximum relaxation of 73 +/- 4% was obtained at 10 Hz. Also in the
      urethra, NANCrelaxation was blocked by L-NOARG (10-5 M), and a contractile
      response generally appeared.6. Detrusor strips treated with alpha-beta methylene
      ATP (10-i M) and atropine (10-6 M), and then contracted by ET-1, showed
      relaxations (19 +/- 3% of the induced tension) in response to electrical field
      stimulation (2-20 Hz) only when the tension was high. No response at all, or
      small contractions, were found in response to electrical stimulation in K+ (35
      mM)-contracted detrusor strips. Detrusor preparations contracted by carbachol
      were concentration-dependently relaxed by exogenously administered NO, SIN-1 (NO
      donor), and isoprenaline, whereas vasoactive intestinal polypeptide had minor
      effects. NO and SIN-1 induced maximal relaxations of 63 +/- 3% and 70 +/- 4%,
      respectively, of the tension induced by carbachol. Isoprenaline produced an
      almost complete relaxation (96 +/- 4%).7. The results suggest that NANC-nerve
      mediated relaxation, involving the L-ARG/NO pathway, can be demonstrated
      consistently in the pig trigonal and urethral, but not in detrusor smooth muscle.
      The importance of this pathway for lower urinary tract physiology and
      pathophysiology remains to be established.

PMID- 1393269
TI  - Study of mechanisms of glucocorticoid hypertension in rats: endothelial related
      changes and their amelioration by dietary fish oils.
AB  - 1. To investigate possible mechanisms of increased systolic blood pressure after
      1 weeks treatment with dexamethasone and its amelioration by fish oil feeding, we
      have examined the reactivity of aortic rings and perfused mesenteric resistance
      vessels. 2. Thirty six Sprague-Dawley rats were initially divided into two groups
      and fed a semisynthetic diet containing either (10% by weight) hydrogenated
      coconut oil and safflower oil mixture (HCO/S) (24 rats) or fish oil (12 rats) for
      5 weeks. From the end of the fourth week, dexamethasone (1.25 mg ml-1) in
      drinking water, was given to half the rats on hydrogenated coconut oil
      (HCO/S+Dex) and to the fish oil-fed group (fish oil+Dex). 3. One week of
      dexamethasone treatment raised systolic blood pressure in the HCO/S+Dex rats but
      not in the fish oil+Dex group. 4. Endothelium-dependent relaxation to
      acetylcholine (ACh) was decreased in aortic rings taken from HCO/S+Dex rats
      compared to rats on HCO/S alone. Relaxant responses to ACh of aortic rings from
      rats given fish oil+Dex were intermediate between the three groups. Aortic
      endothelium-independent responses to sodium nitroprusside (SNP) were unchanged
      between the groups, while aortic contractile responses to noradrenaline were
      similar in all the groups. 5. In the perfused mesenteric resistance artery,
      sensitivity to noradrenaline was decreased in rats given fish oil and
      dexamethasone compared to the other two groups. There were no differences in
      resistance vessel relaxation to ACh or SNP between groups. 6. Serum
      corticosterone levels, used as a marker of dexamethasone absorption, were
      substantially suppressed in dexamethasone-treated rats but levels were higher in
      rats on fish oil than on HCO/S diets. 7. We suggest that the glucocorticoid
      induced rise in systolic blood pressure may be due in part to decreased aortic
      compliance as a consequence of impaired endothelium-dependent relaxation and
      perhaps reduced nitric oxide synthesis. Fish oil feeding may ameliorate this rise
      in blood pressure through (i) changes in dexamethasone absorption, (ii) decrease
      in reactivity to noradrenaline of perfused mesenteric resistance arteries, (iii)
      an increase in endothelium-dependent relaxation to ACh or a combination of these
      three factors.

PMID- 1393270
TI  - Differences in evoked dopamine efflux in rat caudate putamen, nucleus accumbens
      and tuberculum olfactorium in the absence of uptake inhibition: influence of
      autoreceptors.
AB  - 1. Dopamine efflux following single pulse or train of pulse stimulations was
      measured in slices of rat caudate putamen, nucleus accumbens and tuberculum
      olfactorium, using fast cyclic voltammetry at a carbon fibre microelectrode; 1,
      5, 10, 20 or 50 pulses were applied at each location at frequencies varying from
      10 Hz to 500 Hz. 2. There are significant differences in the ability of the
      different regions to increase dopamine efflux following single or repeated
      electrical stimulation. 3. Highest release in response to a single pulse is
      observed in the caudate putamen (approximately 250 nM dopamine), but the ratio of
      the peak dopamine overflow following a train of 20 pulses (50 Hz) when compared
      to a single pulse is rarely greater than three. 4. Release following single pulse
      stimulation in the nucleus accumbens (approximately 185 nM dopamine) is often
      slightly less than in the caudate putamen, but the ratio of peak release when
      trains of 20 pulses (50 Hz) are compared to single pulse stimulation has been as
      great as seven fold. 5. The tuberculum olfactorium releases the least dopamine of
      the three regions following a single pulse stimulation (approximately 40 nM
      dopamine), but the ratio of peak dopamine release following trains of 20 pulses
      (50 Hz) when compared to single pulse can result in a value approaching 20. 6.
      When 20 pulses are applied to the caudate putamen at frequencies ranging from 10
      to 500 Hz, the peak efflux is essentially the same (frequency/release profile is
      flat), with the maximum increase only 140% that of a single pulse.7. By contrast,
      in the nucleus accumbens and the tuberculum olfactorium, well defined
      frequencyrelease relationships are seen following 20 pulses applied at 10, 20 and
      50 Hz; at higher frequencies the dopamine release decreases as frequency is
      increased.8. Experiments with sulpiride or metoclopramide (dopamine D2 receptor
      antagonists) indicate that dopamine release in the caudate putamen is not
      regulated by dopamine autoreceptor activation by endogenous dopamine under our
      experimental conditions (in the absence of reuptake inhibtion). By contrast, in
      the nucleus accumbens and in the tuberculum olfactorium, we present evidence to
      show that at frequencies of stimulation up to 20 Hz, endogenous dopamine acts at
      dopamine autoreceptors to inhibit further release of dopamine but a minimum
      exposure time of between 500 and 1000 ms is needed for the response to D2
      autoreceptor activation by endogenously released dopamine to be seen.

PMID- 1393271
TI  - The role of induction of nitric oxide synthesis in the altered responses of
      jugular veins from endotoxaemic rabbits.
AB  - 1. Endotoxaemia is characterized by hypotension, peripheral vasodilatation and a
      reduced response to vasoconstrictors. Clinical studies have indicated that
      venodilatation contributes to the haemodynamic changes, although there is no
      direct evidence for abnormal venous reactivity. In the present study, the role of
      nitric oxide (NO) in modifying the responses of rabbit isolated jugular veins was
      examined in vitro, 4 h after intravenous injection of endotoxin. 2. Treatment
      with endotoxin reduced the contractile response to the thromboxane-mimetic, 9,11
      dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha (U-46619). This
      affect was endothelium-independent. The response was partially restored by the NO
      synthase inhibitor. NG-monomethyl-L-arginine (L-NMMA 300 microM). 3. Jugular
      veins from control animals did not contract to L-NMMA whereas those from
      endotoxin-treated animals showed concentration-dependent contractions to L-NMMA.
      The contractions produced by L-NMMA were reversed by L-arginine but not by D
      arginine. Treatment of the animals with dexamethasone (4 mg kg-1) 1 h prior to
      administration of endotoxin significantly attenuated the response to L-NMMA. 4.
      The response to sodium nitroprusside did not differ significantly between veins
      from control and endotoxin-treated animals. Endothelial denudation did not alter
      the sensitivity of the veins to sodium nitroprusside. Acetylcholine produced
      endothelium-dependent relaxations which were similar in veins from control and
      endotoxin-treated animals. 5. The results of this study demonstrate that
      intravenous administration of endotoxin induces hyporesponsiveness to U-46619 in
      jugular veins. This effect is mediated, at least in part, by the induction of NO
      synthesis in smooth muscle. The induction is prevented by prior treatment with
      dexamethasone.

PMID- 1393273
TI  - Coeliac haemodynamic effects of endothelin-1, endothelin-3, proendothelin-1 [1
      38] and proendothelin-3 [1-41] in conscious rats.
AB  - 1. Conscious, chronically-instrumented, Long Evans rats were given bolus doses of
      endothelin-1, endothelin-3 (both at 0.01 and 0.1 nmol kg-1), proendothelin-1 [1
      38] and proendothelin-3 [1-41] (both 0.1 and 1 nmol kg-1) in order to compare
      their effects on coeliac haemodynamics, because it has been reported that, in
      conscious dogs, endothelin-1 has paradoxical, prolonged hyperaemic vasodilator
      effects in this vascular bed. Measurements were made also of mesenteric and
      hindquarters haemodynamics for comparison. In a separate experiment, endothelin-1
      (0.1 nmol kg-1) was given before and 20 min after the onset of an infusion of
      mecamylamine (50 mumol kg h-1) to ensure that the responses measured were not
      confounded by rapid reflex changes in autonomic activity. 2. None of the peptides
      caused any increases in coeliac flow or any sustained rises in coeliac vascular
      conductance, although such changes were clear-cut in the hindquarters vascular
      bed following the higher dose of endothelin-1 and endothelin-3. In animals
      treated with mecamylamine the regional haemodynamic effects of the higher dose
      endothelin-1 were not different from those in animals with intact baroreflexes.
      3. Although the lower dose of both endothelin-1 and endothelin-3 caused less
      marked coeliac, than mesenteric vasoconstriction, this difference was not
      apparent with the higher dose of the peptides, or with proendothelin-1 [1-38].
      However, proendothelin-3 [1-41] had less marked coeliac and hindquarters
      vasoconstrictor effects than proendothelin-1 [1-38], in spite of both peptides
      causing similar changes in mesenteric haemodynamics.These differences could have
      been due to regional differences in the conversion of proendothelin-l [1-38] and
      proendothelin-3 [1-41] to endothelin-l and endothelin-3,respectively. Our
      findings contradict the proposition that exogenous proendothelin-3[1-41] is not
      converted into endothelin-3 in vivo.4. Since, in contrast to endothelin-1 and
      endothelin-3, proendothelin-1 [1-38] and proendothelin-3 [1-41] caused only small
      hindquarters vasodilatations, but large vasoconstrictions, it is feasible that
      the vasodilator responses to exogenous endothelin-l and endothelin-3 are
      pharmacological phenomena, and that, in vivo, the production of endothelins from
      proendothelins exerts widespread vasoconstrictor effects.

PMID- 1393272
TI  - Effect of lignocaine on arginine-vasopressin plasma levels: baseline or induced
      by frusemide.
AB  - 1. To assess whether or not lignocaine influences baseline and frusemide-induced
      (5 mg kg-1) plasma concentrations of arginine-vasopressin (AVP), 2 groups of
      rabbits received an infusion of lignocaine (130 micrograms min-1 kg-1) for 6 h.
      Lignocaine-induced changes in AVP plasma concentrations were substantiated by
      measurement of diuresis and natriuresis and hepatic plasma flow, by means of an
      infusion of indocyanine green (ICG) (249 micrograms min-1 kg-1). 2. Baseline
      plasma AVP levels were 4.9 +/- 0.9 pg ml-1 (+/- s.e.), and following lignocaine,
      these values were reduced to 0.7 +/- 0.1 pg ml-1 (P less than 0.01). Frusemide
      increased AVP levels to 134.1 +/- 73.6 pg ml-1 (P less than 0.05) and lignocaine
      totally prevented this increase, e.g. mean AVP levels of 2.7 pg ml-1. 3.
      Lignocaine enhanced baseline diuresis secondary to an increase in free water
      clearance; none of the experimental conditions affected the diuresis and
      natriuresis induced by frusemide. 4. Frusemide reduced the hepatic plasma flow
      and this decrease was not reversed by the infusion of lignocaine. 5. It is
      concluded that in healthy rabbits lignocaine reduces baseline secretion of AVP
      and its antidiuretic effect; in addition, lignocaine prevents the rise in AVP
      induced by frusemide.

PMID- 1393274
TI  - Synergistic anti-nociceptive effect of L-NG-nitro arginine methyl ester (L-NAME)
      and flurbiprofen in the mouse.
AB  - 1. L-NG-nitro arginine methyl ester (L-NAME) administered i.p. produces anti
      nociception in the mouse assessed by the formalin-induced paw licking and acetic
      acid-induced abdominal constriction models. The non-steroidal anti-inflammatory
      drug (NSAID), flurbiprofen, was similarly anti-nociceptive in both models. 2.
      Combination of a sub-threshold dose of L-NAME (10 mg kg-1) with increasing doses
      of flurbiprofen (25- 75 mg kg-1) or a sub-threshold dose of flurbiprofen (50 mg
      kg-1) with increasing doses of L-NAME (10- 100 mg kg-1) resulted in potentiated
      anti-nociception in the formalin model. Combined therapy with sub-threshold doses
      of L-NAME (10 mg kg-1) and indomethacin (10 mg kg-1) also resulted in significant
      anti-nociception. In addition, combining sub-threshold doses of L-NAME (12.5 mg
      kg-1) and flurbiprofen (2 mg kg-1) significantly reduced acetic acid-induced
      abdominal constriction. 3. L-NAME (10 mg kg-1) administered i.p. caused a
      significant (approximately 35%) increase in MAP in the urethane-anaesthetized
      mouse. Flurbiprofen (50 mg kg-1) was inactive. Combination treatment with L-NAME
      (10 mg kg-1) and flurbiprofen (50 mg kg-1) failed to elevate MAP above that
      observed with L-NAME alone. Neither L-NAME (10 mg kg-1) nor flurbiprofen (50 mg
      kg-1) either alone or in combination significantly altered mouse locomotor
      activity. 4. These results suggest that L-NAME and flurbiprofen/indomethacin act
      synergistically in their anti-nociceptive action in the mouse. Combination
      therapy with L-NAME and flurbiprofen and a similar NSAID may provide an
      alternative to the clinical control of pain in man.

PMID- 1393275
TI  - Pituitary adenylate cyclase activating polypeptides, PACAP-27 and PACAP-38:
      stimulators of electrogenic ion secretion in the rat small intestine.
AB  - 1. The effects of pituitary adenylate cyclase activating polypeptide (PACAP)-27
      and PACAP-38 were investigated and compared with vasoactive intestinal
      polypeptide (VIP) responses in voltage clamped preparations of rat jejunum. Under
      these conditions electrogenic ion secretion was continuously recorded. 2. PACAP
      27 is the most potent secretagogue described thus far, exhibiting a concentration
      dependent dual secretory action. At low concentrations it stimulated rapid,
      transient secretory responses (not seen with either PACAP-38 or VIP) and these
      were inhibited by tetrodotoxin (TTX). At higher nM concentrations of PACAP-27
      more prolonged secretory responses predominated which were insensitive to TTX. 3.
      In the presence of TTX, the concentration-response curve to PACAP-27 gave an EC50
      value of 29.4 +/- 5.4 nM (n = 4) compared with 0.8 +/- 0.1 nM (n = 9) for PACAP
      27 alone and 30.6 +/- 5.6 nM (n = 5) for PACAP-38. C-terminal fragments of PACAP
      38 were not significantly effective. 4. Blockade of muscarinic and nicotinic
      receptors partially inhibited the low concentration effects of PACAP-27.
      Substance P desensitization and capsaicin pretreatment were effective at
      inhibiting the transient secretory PACAP-27 responses. Evidence is presented for
      selective, high affinity PACAP-27 receptors on submucous neurones innervating the
      mucosal region of the rat jejunum.

PMID- 1393276
TI  - Human bronchial cyclic nucleotide phosphodiesterase isoenzymes: biochemical and
      pharmacological analysis using selective inhibitors.
AB  - 1 The aims of the present study were to characterize the cyclic nucleotide
      phosphodiesterase (PDE) isoenzyme activities present in human bronchi and to
      examine the ability of selective isoenzyme inhibitors to relax histamine and
      methacholine precontracted preparations of human bronchi. 2 Three separations of
      pooled human bronchial tissue samples were performed. Ion-exchange chromatography
      showed that the soluble fraction of human bronchial preparations contains PDE I,
      II, III, IV and V isoenzyme activities. Multiple forms of PDE I and PDE IV were
      observed and PDE IV was the main cyclic AMP hydrolytic activity. 3 3-Isobutyl-l
      methylxanthine (IBMX) non-selectively inhibited all separated isoenzyme
      activities. Zaprinast selectively inhibited PDE V, but also effectively inhibited
      one of the two PDE I isoforms identified. The PDE IV selective inhibitors
      rolipram and RO-201724, inhibited the PDE IV activities as did the dual PDE
      III/IV inhibitor, Org 30029. Org 9935, a PDE III selective inhibitor, potently
      attenuated part of the PDE IV activity peak in one of three separations
      performed, indicating that some PDE III activity may co-elute with PDE IV under
      the experimental conditions employed. 4 PDE IV-selective (rolipram), PDE III
      selective (Org 9935) and dual PDE III/IV (Org 30029) inhibitors were effective
      relaxants of human bronchial smooth muscle. The PDE V/PDE I inhibitor, zaprinast
      was relatively ineffective. 5 The present study demonstrates in human bronchi, as
      in animal airways smooth muscle, that inhibitors of PDE III, PDEIV and dual PDE
      III/IV have potentially useful bronchodilator activity and are worthy of further
      consideration as anti-asthma drugs.

PMID- 1393277
TI  - Altered microvascular reactivity to endothelin-1, endothelin-3 and NG-nitro-L
      arginine methyl ester in streptozotocin-induced diabetes mellitus.
AB  - 1 We have determined the dermal microvascular effects of the nitric oxide (NO)
      synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 100 nmol/site),
      endothelin-1 (ET-1, 0.1-10 pmol/site) and ET-3 (0.1-30 pmol/site) in rats with
      streptozotocin (STZ)-induced diabetes mellitus. Cutaneous blood flow changes as
      measured by a 133xenon (133Xe) clearance technique, were determined in diabetic
      rats four weeks after treatment with streptozotocin (STZ) and compared with
      responses measured in normal rats four weeks after treatment with saline. 2
      Resting skin blood flow was similar in diabetic and in normal rats, as measured
      by 133Xe clearance and laser Doppler flowmetry. 3 Intradermal NG-nitro-L-arginine
      methyl ester (L-NAME) reduced skin blood flow in normal rats by 55.2 +/- 2.6% as
      measured by 133Xe clearance, (n = 9). L-NAME was significantly less effective in
      diabetic rats, inducing a 40.9 +/- 7.7% decrease in blood flow (n = 9, P less
      than 0.05). The enantiomer D-NAME had no effect in either group of rats. 4 Low
      doses of ET-1 and ET-3 injected intradermally induced dose-dependent decreases in
      blood flow, measured by 133Xe clearance, which were similar in both groups of
      rats. However, the responses to the highest doses of ET-1 (10 pmol/site) and ET-3
      (10 and 30 pmol/site) were significantly reduced in the diabetic compared with
      the normal rats (P less than 0.05).In addition vasoconstriction to the highest
      doses of vasopressin (0.3 and 3 pmol/site) and vasodilatation to the neuropeptide
      calcitonin gene-related peptide (CGRP, 1O pmol/site) were similarly reduced in
      the diabetic rats (P <0.05).5. The decrease in blood flow induced by submaximal
      doses of ET-1 was enhanced by co-injection with L-NAME (100 nmol/site) in both
      diabetic and normal rats. However, this enhanced response was significantly
      reduced in the diabetic rats (P<0.05). A similar pattern of responses were
      observed to ET-3 in the presence and absence of L-NAME.6. These results indicate
      that the cutaneous microvasculature of rats with STZ-induced diabetes responds
      differently to intradermal ET-1 and ET-3 compared with normal rats; a similarly
      altered vascular reactivity was observed with vasopressin and CGRP. Hence, the
      diabetic microcirculation has impaired responses to several vasoconstrictors and
      a vasodilator. The effect of the nitric oxide synthase inhibitor L-NAME is also
      suppressed in the diabetics, suggesting that there may be decreased local
      production of, or response, to nitric oxide.

PMID- 1393278
TI  - Pharmacological evidence for distinct endothelin receptors in guinea-pig bronchus
      and aorta.
AB  - The ETA receptor antagonist, BQ-123 (1 microM) potently antagonized endothelin-1
      (ET-1) concentration-response curves in guinea-pig aorta (pKB = 7.1). However, 10
      microM BQ-123 was without effect on ET-1-induced contractions in guinea-pig
      bronchus. The ETB-selective agonist, sarafotoxin S6c did not contract the aorta
      but was a potent and effective contractile agonist in the bronchus. BQ-123 (10
      microM) was without effect on sarafotoxin S6c-induced contractions in the
      bronchus. These data provide evidence for distinct endothelin receptors in guinea
      pig aorta and bronchus, which appear to be predominantly of the ETA and non-ETA,
      perhaps ETB, subtypes, respectively.

PMID- 1393279
TI  - The mechanism by which procaine inhibits catecholamine secretion from bovine
      chromaffin cells.
AB  - 1. We have investigated the action of procaine on stimulus-secretion coupling in
      bovine adrenal chromaffin cells. 2. Procaine inhibited the catecholamine
      secretion evoked by 500 microM carbachol (CCh) with an IC50 of 35 microM and the
      associated calcium influx (IC50 60 microM). It inhibited the catecholamine
      secretion evoked by depolarization with high potassium by less than 20% even at
      the highest concentrations tested (3.2 mM). 3. The secretion evoked by CCh was
      associated with an increase in sodium influx. This evoked influx was also
      inhibited by procaine (IC50 80 microM). 4. This selective action of procaine on
      the CCh-evoked catecholamine secretion was investigated further by patch-clamp
      techniques. 5. In agreement with the ion flux studies, procaine inhibited the
      inward current evoked by CCh. Procaine also altered the spectral characteristics
      of the noise associated with the agonist-induced current by adding an additional
      high frequency component. The amplitude of this component showed an e-fold
      increase for a 55 mV membrane hyperpolarization. 6. Data from cell-attached
      patches showed that increasing concentrations of procaine produced a progressive
      fall in the mean channel open time and an increase in mean blocked time. This
      combination led to a decrease in mean burst length. In addition, Popen was
      reduced by 50 microM procaine. These changes in channel conducting time were
      sufficient to account for the reduction in inward current. A limited study of the
      action of procaine on nicotinic channels in outside-out patches gave similar
      results. 7. The data were considered in relation to various schemes of
      anaesthetic-channel interactions. The data did not fit the sequential blocking
      model or the extended channel block model but could be fitted to a modified
      sequential blocking model in which the rate constant for channel reopening after
      block was itself subject to modulation by the anaesthetic and the blocked channel
      could close without passing through the open state.

PMID- 1393280
TI  - Tracheal relaxation induced by potassium channel opening drugs: its antagonism by
      adrenergic neurone blocking agents.
AB  - 1. We have studied the ability of some adrenergic neurone blocking agents to
      inhibit the tracheal relaxant actions of isoprenaline, theophylline and the
      potassium channel openers (KCOs) BRL 38227, pinacidil and RP 52891. 2. BRL 38227,
      isoprenaline, pinacidil, RP 52891 and theophylline each caused concentration
      dependent suppression of the spontaneous tone of guinea-pig isolated trachealis.
      The maximal relaxant effects of isoprenaline and pinacidil were equal to that of
      theophylline. In contrast, the maximal effects of BRL 38227 and RP 52891 were
      approximately 85-95% of that of theophylline. 3. Guanethidine (5-500 microM) did
      not itself modify the spontaneous tone of the trachealis muscle but antagonized
      BRL 38227 in a concentration-dependent manner. Guanethidine (50 microM) also
      antagonized pinacidil and RP 52891. However, guanethidine did not antagonize
      either isoprenaline or theophylline. 4. Bretylium (50 microM) did not itself
      modify the spontaneous tone of the trachealis muscle but antagonized BRL 38227,
      pinacidil and RP 52891. Bretylium did not antagonize either isoprenaline or
      theophylline. 5. Guanidine (50 and 500 microM) did not itself modify the
      spontaneous tone of the trachea and failed to modify the tracheal relaxant
      activity both of BRL 38227 and theophylline. 6. BRL 38227 (1 and 10 microM)
      stimulated, in a concentration-dependent manner, the efflux of 86Rb+ from strips
      of bovine trachealis muscle that had been pre-loaded with the radiotracer.
      Guanethidine (50 microM), bretylium (50 microM) and debrisoquine (50 microM) did
      not themselves modify the efflux of 86Rb+ from bovine trachealis but each of
      these agents markedly inhibited the stimulant effect of BRL 38227 (10 microM) on
      86Rb+ efflux.7. It is concluded that the adrenergic neurone blocking agents
      guanethidine and bretylium can inhibit the tracheal relaxant actions of KCOs such
      as BRL 38227, pinacidil and RP 52891 without antagonizing isoprenaline or
      theophylline. The ability of the adrenergic neurone blocking agents to antagonize
      BRL 38227 in promoting 86Rb+ efflux from trachealis muscle may suggest that the
      adrenergic neurone blocking agents act to prevent the opening of the plasmalemmal
      K+-channel that is involved in the tracheal relaxant actions of the KCOs.

PMID- 1393281
TI  - The contribution of charge to affinity at functional (M3) muscarinic receptors in
      guinea-pig ileum assessed from the effects of the carbon analogue of 4-DAMP
      methiodide.
AB  - 1. 4-Diphenylacetoxy-1:1-dimethyl cyclohexane (carbo-4-DAMP) is the carbon
      analogue of 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methiodide. The
      compounds differ only in that the quaternary nitrogen atom in 4-DAMP methiodide
      is replaced by a quaternary carbon atom, which is uncharged. 2. Carbo-4-DAMP
      appears to act competitively at functional (M3) muscarinic receptors in guinea
      pig ileum. Estimates of log affinity constant are 6.0 at 30 degrees C and 5.9 at
      37 degrees C, i.e. the compound has 0.1% of the affinity of 4-DAMP methobromide.
      3. The absence of charge makes little difference to the conformation as
      determined by X-ray crystallography. The bond lengths and angles are very
      similar, though the bonds in the cyclohexane ring of carbo-4-DAMP are
      consistently slightly longer than those in the piperidinium ring of 4-DAMP
      methiodide, and the presence of the charge slightly reduces the space between
      molecules. 4. The difference between the affinities of 4-DAMP methobromide and
      carbo-4-DAMP indicates that the contribution of coulombic forces to the binding
      between 4-DAMP methiodide and muscarinic (M3) receptors is at least 17 kJ mol-1
      (4.1 kcal mol-1) at 37 degrees C. How much this is an underestimate depends upon
      how much hydrophobic binding is greater with the uncharged compound.

PMID- 1393282
TI  - Ca(2+)-stores mobilization by diadenosine tetraphosphate, Ap4A, through a
      putative P2Y purinoceptor in adrenal chromaffin cells.
AB  - 1. Diadenosine tetraphosphate (Ap4A) evoked a concentration-dependent increase in
      cytosolic [Ca2+] in resting chromaffin cells. The EC50 value for this action was
      28.2 +/- 6.6 microM. This effect was also produced by diadenosine pentaphosphate
      (Ap5A) with an EC50 of 50 +/- 7 microM. 2. In contrast with this effect,
      pretreatment with Ap4A or Ap5A induced a 30% reduction in Ca2+ entry following 10
      microM dimethylphenylpiperazinium. 3. The elevation in cytosolic [Ca2+] induced
      by Ap4A was persistent in approximately 100 nM external [Ca2+] and was sensitive
      to depletion of internal Ca2+ stores by a bradykinin prepulse or whole cell
      depletion in Ca2+. 4. The effect of Ap4A was mimicked and desensitized by the
      agonist adenosine 5'-O-(2-thiodiphosphate), and blocked by the P2Y-receptor
      antagonist, cibachrome blue. The P2X-receptor agonist alpha,beta-methylene
      adenosine 5'-triphosphate was inactive both by itself or in combination with
      Ap4A. This is compatible with a P2Y-purinoceptor-mediated action.

PMID- 1393284
TI  - The nucleotide receptors on mouse C2C12 myotubes.
AB  - 1. The response of C2C12 mouse myotubes to stimulation with adenosine
      triphosphate (ATP) and other nucleotides was studied by measuring changes in
      membrane potential. 2. A transient hyperpolarization followed by a slowly
      declining depolarization of the cells was observed in the presence of ATP (10
      microM-1 mM). 3. The hyperpolarization was not observed in the absence of
      external calcium, and was abolished in the presence of tetraethylammonium (20 mM)
      or the bee toxin, apamin (0.1 microM). The depolarization was reduced under low
      sodium conditions. 4. A biphasic change in membrane potential was also recorded
      in the presence of adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) and the
      pyrimidine uridine triphosphate (UTP), while the ATP derivatives and analogues,
      adenosine diphosphate, adenosine, alpha,beta-methylene ATP and 2-methylthio ATP
      and the nucleotides, guanosine triphosphate and cytidine triphosphate, did not
      affect the membrane potential of the myotubes. 5. The hyperpolarization elicited
      by ATP gamma S or UTP was also blocked by apamin and abolished under Ca(2+)-free
      conditions. 6. In contrast to ATP and ATP gamma S, the depolarization evoked by
      UTP was unaffected under low Na+ and less sensitive to the antagonistic action of
      suramin. 7. The ATP and UTP responses at maximal concentration were not additive
      after simultaneous application. ATP elicited a depolarization if applied after
      UTP, while UTP did not change membrane potential following the application of
      ATP. 8. The concentration-response curves of the effective nucleotides were
      shifted to the right in the presence of suramin, suggesting competitive
      antagonism.9. These results can be explained by the presence of 'nucleotide
      receptors' mediating the ATP/UTPinduced hyperpolarization and depolarization in
      C2C12 myotubes. Furthermore, an increase in Na+-conductivity can be exclusively
      activated by ATP.

PMID- 1393283
TI  - Modulation by opioids and by afferent sensory neurones of prostanoid protection
      of the rat gastric mucosa.
AB  - 1. Pretreatment with capsaicin, to deplete sensory neuropeptides from primary
      afferent neurones or the administration of morphine (9 mg kg-1, i.v.), which can
      inhibit neuropeptide release, augmented gastric mucosal injury induced by a 5 min
      challenge with intragastric ethanol in the rat, as assessed by macroscopic and
      histological evaluation. 2. Morphine administration substantially attenuated the
      protective actions of the prostaglandin analogue 16,16 dimethyl prostaglandin E2
      (dm PGE2; 0.5-20 micrograms kg-1, p.o.) against ethanol-induced damage. This
      reduced degree of protection by dmPGE2 was not however, the consequence of the
      enhanced level of damage. 3. These actions of morphine in reducing prostaglandin
      protection against mucosal injury were abolished by pretreatment (5 min) with
      naloxone (1 mg kg-1, i.v.) or the peripherally acting opioid antagonist, N-methyl
      nalorphine (6 mg kg-1, i.v.). 4. Capsaicin pretreatment (2 weeks before study),
      likewise attenuated the protective actions of dmPGE2, although to a lesser degree
      than did morphine. 5. These findings, thus implicate the involvement of capsaicin
      and opioid-sensitive afferent neurones in the processes by which exogenous
      prostanoids can protect the gastric mucosa from damage.

PMID- 1393285
TI  - Noradrenaline-stimulated inositol phosphate accumulation in arteries from
      spontaneously-hypertensive rats.
AB  - 1. The effects of noradrenaline upon polyphosphoinositide (PPI) breakdown was
      investigated by measuring the accumulation of inositol phosphates (IPs) in tail
      arteries from normo- (WKY) and spontaneously-hypertensive (SHR) rats. 2.
      Noradrenaline (10(-7)-10(-3) M) evoked a concentration-dependent increase in
      total IP accumulation in both WKY and SHR rats but no significant differences
      between the populations were detected. 3. In contrast, significant differences in
      the accumulation of the individual IPs, which contributed to the total IP,
      occurred. A significantly greater noradrenaline-stimulated accumulation of
      inositol trisphosphate (IP3) was observed in tissues from SHR compared with those
      from WKY rats at each effective concentration of noradrenaline. This was
      paralleled by an equivalent reduction in inositol monophosphate (IP1)
      accumulation, consistent with the lack of a significant difference in
      noradrenaline-stimulated total IP accumulation between the two populations. 4. In
      time course studies, an enhanced noradrenaline-induced accumulation of IP3, in
      SHR compared to WKY rats, occurred from the earliest time point studied after the
      addition of the catecholamine both in the presence and absence of LiCL (10 mM).
      In the presence of LiCl (10 mM) no significant difference in noradrenaline-evoked
      total IP accumulation between SHR and WKY rats was observed; in the absence of
      LiCl noradrenaline-evoked a greater total IP accumulation in SHR than in WKY rats
      at all time points investigated. 5. These studies suggest that the main reason
      for the enhanced noradrenaline-induced accumulation of IP3 in arteries from SHR
      rats is a reduced rate of dephosphorylation of both IP3 and inositol bisphosphate
      (IP2) rather than a greater formation of IP3 from PPIs.6. This enhanced
      accumulation of IP3 may result in an increased calcium mobilisation accounting
      for the increased contractility to noradrenaline of tail arteries from SHR as
      compared with those from WKY rats.

PMID- 1393286
TI  - Investigation of the 5-hydroxytryptamine receptor mediating the 'maintained'
      short-circuit current response in guinea-pig ileal mucosa.
AB  - 1. 5-Hydroxytryptamine (5-HT) stimulated a biphasic increase in short-circuit
      current (SCC) in guinea-pig isolated ileal mucosa. The initial 'spike' response
      to 5-HT was inhibited by tetrodotoxin (0.3 microM). We have investigated the 5-HT
      receptor mechanism(s) controlling the second 'maintained' component of the
      response which remained after treatment with tetrodotoxin. 2. 5-HT stimulated
      concentration-related increases in SCC with an EC50 value of 5.4 microM. Isobutyl
      methylxanthine (IBMX, 10 microM) produced a six fold leftward shift of this
      concentration-response curve, suggesting the involvement of a cyclic
      nucleotide(s) in these responses. 3. In the presence of IBMX, 5-HT stimulated
      reproducible increases in SCC with an EC50 value of 0.9 microM. The rank order of
      potency of indole agonists in these tests was 5-HT greater than or equal to 5
      methoxytryptamine greater than 5-carboxamidotryptamine = alpha-methyl-5-HT much
      greater than 2-methyl-5-HT. 4. The substituted benzamides were partial agonists.
      Metoclopramide and cisapride produced approximately 20% of the 5-HT maximum, and
      renzapride and R,S-zacopride produced approximately 50% of the 5-HT maximum.
      Metoclopramide and cisapride inhibited the SCC responses to 5-HT with apparent
      pKB values of 4.8 and 7.0 respectively. 5. The SCC responses to 5-HT were not
      inhibited by antagonists selective for 5-HT1 (methysergide, methiothepin), 5-HT2
      (ketanserin) or 5-HT3 (ondansetron, ICS205-930) receptors. 6. The SCC responses
      to 5-methoxytryptamine, 5-carboxamidotryptamine, alpha-methyl-5-HT and R,S
      zacopride, but not 5-HT, were selectively inhibited by high concentrations of
      ICS205-930 with apparent pKB values of approximately 6.7. A possible
      interpretation of these results is that the 'maintained' SCC response to 5-HT is
      mediated by a heterogeneous population of 5-HT receptors. One of these receptors
      exhibits the characteristics of the putative 5-HT4 receptor.

PMID- 1393287
TI  - Contractile activity of big endothelin-1 on the human isolated bronchus.
AB  - 1. We have studied the contractile activity of the 39 amino acid precursor of
      endothelin-1 (ET-1), big endothelin-1 (big ET-1), on human isolated bronchi. The
      contribution of the metalloproteases, neutral endopeptidase (NEP) and angiotensin
      converting enzyme (ACE), in the presence or absence of the epithelium lining, by
      use of specific inhibitors, was also evaluated on the effects of big ET-1. 2. Big
      ET-1 elicited a potent contraction of human isolated bronchus. The -log EC50
      value for big ET-1 was 7.53 +/- 0.08 (n = 11) and Emax 78.5 +/- 3.8% (% of ACh
      3mM). 3. Incubation of human isolated bronchi with the NEP inhibitor
      phosphoramidon (10(-5) M) induced a rightward shift of the concentration-response
      curve induced by big ET-1 (10(-9) M to 3 x 10(-7) M). Similar results were
      observed when human bronchi were incubated with thiorphan (10(-5) M), but the
      shift to the right was significantly less (P less than 0.01) than that observed
      in the case of phosphoramidon (-0.35 +/- 0.05 vs -0.67 +/- 0.07 log unit). 4. The
      two inhibitors of angiotensin I converting enzyme (ACE), captopril or enalapril
      diacid, did not affect the concentration-response curve for contraction induced
      by big ET-1. 5. When the epithelium was removed, a leftward shift of the
      concentration-response curve of big ET-1 (10(-9) M to 3 x 10(-7) M) was observed.
      Incubation of human isolated bronchi with phosphoramidon or thiorphan (10-5M) or
      with enalapril diacid or captopril did not modify the leftward shift of the
      concentration-response curve for big ET-1 after epithelium removal.6. These
      results suggest that big ET-1 elicits potent contractile activity in the human
      isolated bronchus and that its effect is the consequence of the conversion to ET
      1 by a phosphoramidon-sensitive metalloprotease which, although different from
      NEP and ACE, appears to be similar to the endothelinconverting enzyme (ECE)
      described in other studies in animals.

PMID- 1393288
TI  - Actions of 5-hydroxytryptamine and 5-HT1A receptor ligands on rat dorso-lateral
      septal neurones in vitro.
AB  - 1. The actions of 5-hydroxytryptamine (5-HT) and some 5-HT1A receptor ligands on
      neurones in the rat dorso-lateral septal nucleus were recorded in vitro by
      intracellular recording techniques. 2. In the presence of tetrodotoxin (1 microM)
      to block any indirect effects, bath application of 5-HT (0.3-30 microM)
      hyperpolarized the neurones in a concentration-dependent manner and reduced
      membrane resistance. The hyperpolarization did not exhibit desensitization and
      was sometimes followed by a small depolarization. 3. The 5-HT1A receptor ligands,
      8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), N,N-dipropyl-5
      carboxamidotryptamine (DP-5-CT) and buspirone but not the non-selective 5-HT1
      receptor agonist, 1-m-trifluoromethylphenylpiperazine (TFMPP), also
      hyperpolarized the neurones. 4. 5-HT, 8-OH-DPAT and DP-5-CT appeared to act as
      full agonists whereas buspirone behaved as a partial agonist. The estimated EC50S
      were: DP-5-CT 15 nM, 8-OH-DPAT 110 nM, 5-HT 3 microM and buspirone 110 nM. 5. At
      a concentration of 3 microM, the putative 5-HT1A receptor antagonists, spiperone,
      methiothepin, NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-pthalimido)butyl]piperazine)
      and MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl-methylamino)ethyl]-8-
      azaspiro[4,5]decane-7,9-dione methyl sulphonate), produced a parallel rightward
      shift in the concentration-response curve to 5-HT with no significant reduction
      in the maximum response. The estimated pA2 values were: NAN-190 6.79, MDL 73005EF
      6.59, spiperone 6.54 and methiothepin 6.17.6. The 5-HT2/5-HTlc receptor
      antagonist, ketanserin (3 microM) and the 5HT3 receptor antagonist, tropisetron
      (3 microM) did not antagonize the 5-HT-induced hyperpolarizations; however,
      ketanserin blocked the depolarization which sometimes followed the
      hyperpolarization.7. It is concluded that the 5-HT-induced membrane
      hyperpolarization of rat dorso-lateral septal neurones is mediated by 5-HTA
      receptors.

PMID- 1393289
TI  - Potentiation of ADP-induced aggregation in human platelet-rich plasma by 5
      hydroxytryptamine and adrenaline.
AB  - 1. We have used dose-response curves to quantitate the potentiation of adenosine
      5'-diphosphate (ADP)-induced aggregation and thromboxane (TXA2) generation by 5
      hydroxytryptamine (5-HT) and adrenaline in human citrated platelet-rich plasma.
      We have also quantitated the inhibition of these responses by aspirin, ketanserin
      and yohimbine, singly and in pairs. 2. Ketanserin (5 microM) inhibited TXA2
      production and the second wave of platelet aggregation induced by a range of
      concentrations of ADP alone. This indicates that endogenous 5-HT, released from
      the platelet dense granules, contributes significantly to responses induced by
      ADP. 3. When 5-HT (10 microM) was added before ADP, a lower concentration of ADP
      was required to cause 50% aggregation and TXA2 generation. The ratio of ADP
      concentrations (CR) to cause 50% aggregation in the presence and absence of 5-HT
      was 2.1 when only added 5-HT was considered, and 5.0 when endogenous 5-HT was
      also taken into account. 4. Potentiation of ADP-induced aggregation by 5-HT also
      occurred in the presence of aspirin, resulting in a CR of 2.3. As expected,
      ketanserin inhibited potentiation by 5-HT in the presence and absence of aspirin.
      Although aspirin caused substantial inhibition of aggregation induced by ADP and
      5-HT (CR 3.4), further inhibition occurred when ketanserin was also present (CR
      6.5). 5. A subthreshold concentration of adrenaline (0.25 microM) caused
      substantial potentiation of ADP-induced aggregation in the absence (CR 4.0) and
      presence (CR 2.0) of aspirin. As expected, yohimbine (9 microM) inhibited this
      potentiation.Maximum TXA2 generation induced by ADP increased from 32.5 to 59.4
      pg per 106 platelets when adrenaline was present. Aggregation induced by ADP and
      adrenaline was markedly inhibited by aspirin (CR 5.1) but was further inhibited
      when yohimbine (9 microM) was also present (CR 10.0).6. Results from this in
      vitro study show ketanserin and yohimbine have the potential to be used in
      combination with aspirin as antithrombotic agents in vivo.

PMID- 1393291
TI  - The influence of endothelin-1 on human foeto-placental blood vessels: a
      comparison with 5-hydroxytryptamine.
AB  - 1. The vasoconstrictor effect of endothelin-1 (3 x 10(-11) M-10(-7) M) was
      studied in successive generations of blood vessels of the foeto-placental
      vascular tree. These were the human umbilical arteries and veins, primary surface
      chorionic plate arteries, secondary chorionic plate arteries, tertiary surface
      chorionic plate arteries and veins and the secondary stem villus arterioles. The
      responses to endothelin-1 were compared with those to 5-hydroxytryptamine (10(-9)
      M-10(-5) M). Arterial preparations were gassed with 2.5% O2, 8% CO2 balance N2
      and venous preparations were gassed with 5% O2, 6% CO2 balance N2 to simulate the
      conditions prevalent in utero. The influence of increasing the oxygen tension to
      16% (that prevalent at birth) on the response to endothelin-1 on the umbilical
      arteries was also investigated. 2. All the arterial vessels tested were some ten
      times more sensitive to endothelin-1 than to 5-hydroxytryptamine and the venous
      preparations were ten times more sensitive to endothelin-1 than were their
      equivalent arteries. Increasing oxygen tension did not affect the responses to
      endothelin-1 in the umbilical artery. 3. Whilst the amplitude of the endothelin-1
      induced response was uniform throughout the foetoplacental vascular tree,
      including the stem villus arterioles, the maximum response to 5-hydroxytryptamine
      decrease with successive generations and it had no significant effect on the stem
      villus arterioles.The ratios of the responses to 10- M endothelin-1: 10-7M 5
      hydroxytryptamine in human umbilical arteries, primary surface chorionic plate
      arteries, secondary chorionic plate arteries,tertiary surface chorionic plate
      arteries and the secondary stem villus arterioles in the vessels (listed in order
      of decreasing vessel size) were 1:1.2, 1:0.36, 1:0.33, 1:0.35 and 1:0.04
      respectively.4. In conclusion, endothelin-1 is a powerful vasoconstrictor at all
      levels of the foeto-placental vascular system including the stem villus
      resistance vessels. It may play an important role in maintaining foeto-plancental
      vascular resistance at the low oxygen tension which exists in this vascular
      system in utero.

PMID- 1393290
TI  - Effects of K+ channel blockers on the action potential of hypoxic rabbit
      myocardium.
AB  - 1. In order to assess the role of different ionic currents in hypoxia-induced
      action potential shortening, we investigated the effects of blockers of voltage
      dependent and ATP-sensitive K(+)-channel on the membrane potential of hypoxic
      rabbit hearts and papillary muscles. The response to blocking of the inward
      rectifier was studied at three external K+ concentration: 2.5, 5, and 7.5 mM. 2.
      Hypoxia produced a progressive decline in action potential duration (APD) that
      levelled off after 15 to 20 min. Steady state APD values at 25% and 95%
      repolarization (APD25 and APD95) were 26.0 +/- 1.9% and 42.2 +/- 2.4% of controls
      respectively. 3. Tetraethylammonium (TEA, 10 mM) delayed but did not reduce APD
      shortening at the steady state. 4. Blocking of IK1 with a mixture of 0.2 mM Ba2+
      and 4 mM Cs+ lengthened APD in normoxia and prevented APD95 shortening in
      hypoxia. The APD25 shortening was significantly attenuated at all [K]o. 5.
      Glibenclamide (Glib, 30 microM) did not prevent APD shortening, but produced a
      progressive action potential (AP) lengthening after 15 min of hypoxia. Steady
      levels of 48 +/- 3.5% and 62 +/- 5.0% of controls for APD25 and APD95
      respectively were reached after 45 min. 6. The relation between APD25 and pacing
      rate was determined in normoxic and hypoxic papillary muscles and the effects of
      2 mM 4-aminopyridine (4-AP) were examined. Hypoxia attenuated the APD25
      shortening currently observed when the stimulation rate was lowered from 1 to 0.1
      Hz without altering the plateau reduction occurring at frequencies above 2 Hz.
      These effects were potentiated by 4-AP.7. Our data suggest that the accelerated
      AP repolarization in hypoxic rabbit myocardium represents a delicate balance of
      several outward currents: IKI, IK-ATP. and at least one yet unidentified current
      component rather insensitive to changes in [K]o and to K+ channel blockers.

PMID- 1393292
TI  - Regional differences in endothelin converting enzyme activity in rat brain:
      inhibition by phosphoramidon and EDTA.
AB  - 1. It has been demonstrated previously that conversion of big endothelin-1 (bET
      1) to endothelin-1 (ET-1) is inhibited in vitro and in vivo by phosphoramidon. In
      addition, ET-1 binding sites and mRNA have been shown within the brain. Here we
      expand upon our previous observation that rat brain contains phosphoramidon
      inhibitable endothelin converting enzyme (ECE) and show that this activity is not
      uniformly distributed throughout the brain. 2. ECE activity was detected by a
      bioassay which depended upon the 10,000 fold difference in potency between bET-1
      and ET-1 as stimulants of guanosine 3':5'-cyclic monophosphate (cyclic GMP)
      accumulation in kidney epithelial (PK1) cells of the pig. Data were confirmed by
      specific enzyme-linked immunosorbent assay (ELISA) employing antibody directed
      against ET-1/3(17-21). 3. Following homogenization of the whole brain and
      ultracentrifugation the 100,000 g pellet contained greater than 4 times more ECE
      activity than the cytosol. Washing of the pellet with KCl (1 M) and extraction
      with the detergent CHAPS (20 mM) revealed a phosphoramidon-inhibitable ECE within
      the residual particulate fraction (nominally classified as the cytoskeletal
      fraction). Phosphoramidon (IC50, approx. 5 microM) or EDTA inhibited the
      conversion of bET-1 to ET-1 by the cytoskeletal fraction of rat brain by more
      than 60%.2+ 4. Following dissection of rat brain into olfactory bulb, cerebral
      cortex, striatum, hippocampus, cerebellum, midbrain (including thalamus),
      hypothalamus and medulla oblongata (including pons) the greatest ECE was detected
      in the hypothalamus and medulla oblongata.After fractionation, the ECE-activities
      in the cytoskeletal fractions prepared from the hypothalamus or medulla oblongata
      were inhibited concentration-dependently by phosphoramidon or EDTA, with maximum
      inhibitions of>80% and >70%, respectively.5. These data show that rat brain
      contains a phosphoramidon- and EDTA-inhibitable ECE which maybe similar to that
      present in endothelial cells. The localization of this enzyme correlates with
      published reports of immunoreactive-ET-l, ET-1-binding sites, and messenger RNA
      for ET-1 in the rat brain, and suggests the presence of the entire synthetic
      pathway for ET-1.

PMID- 1393293
TI  - Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and
      rabbit ventricular cells.
AB  - 1. The actions and mechanisms of action of novel analogues of sotalol which
      prolong cardiac action potentials were investigated in guinea-pig and rabbit
      isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds
      significantly prolonged action potential duration at 20% and 90% repolarization
      levels without affecting resting membrane potential. In guinea-pig but not rabbit
      cells there was an increase in action potential amplitude and in rabbit cells
      there was no change in the shape or position of the 'notch' in the action
      potential. 3. Possible mechanisms of action were studied in more detail in the
      case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4
      dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration
      continued to occur in the presence of nisoldipine, and calcium currents recorded
      under voltage-clamp conditions were not reduced by compound II (1 microM). Action
      potential prolongation by compound II was also unaffected in the presence of 10
      microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed
      from the current during ramp changes in membrane potential (20 mV s-1) over the
      range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed
      rectifier potassium current (IK) activated by step depolarizations and recorded
      as an outward tail following repolarization. When a submaximal concentration (50
      nM) was applied there was no change in the apparent reversal potential of IK.6.
      Submaximal concentrations of compound II were without effect on activation of IK
      with time at a membrane potential of + 40 mV, and no changes were detected in the
      time constants of the two components of IK decay over the range of potentials -
      60 to 0 mV. Compound 11 (50 nM) appeared to cause a small shift in the activation
      of IK with membrane potential (an apparent shift of approximately 10mV in the
      depolarizing direction at the mid-point of the curve).7. Log dose-response curves
      for action potential prolongation and for blockade of IK by compound II were
      similar. The IC50 for compound II was approximately 30 nM.8. It is concluded that
      this novel series of compounds prolongs action potential duration, and that in
      the case of compound II the evidence supports a potent selective effect on the
      time-dependent potassium current IK, an effect which can account for this
      prolongation.

PMID- 1393294
TI  - In vitro inhibition by endothelins of thrombin-induced aggregation and Ca2+
      mobilization in human platelets.
AB  - 1. The in vitro effects of endothelins (ET-1 and ET-3) on human platelets were
      investigated by measurement of the aggregatory responses of washed platelets to
      thrombin and by the determination of cytosolic pH (pHi) and free Ca2+
      concentration ([Ca2+]i) determined with the fluorescent indicators, BCECF and
      Fura-2. 2. ET-1 and ET-3 at concentrations ranging from 10(-10) to 5 x 10(-7) M,
      did not promote platelet aggregation but inhibited in a dose-dependent manner the
      aggregation induced by 0.05 u ml-1 thrombin (P less than 0.002 and less than
      0.001, respectively) with maximal effects reached at 10(-8) M (17 +/- 3 and 15 +/
      2%, n = 11, P = 0.002 for each). 3. Even at 5 x 10(-7) M, ET-1 and ET-3 did not
      cause a measurable change in basal [Ca2+]i and pHi. When tested in combination
      with thrombin, 5 x 10(-7) M ET-1 and ET-3 decreased the transient peak of [Ca2+]i
      by 17 +/- 7 and 28 +/- 7% (n = 7 and 11, P = 0.03 and P = 0.002). No effect on
      pHi variations was detected. In the virtual absence of external Ca2+, 5 x 10(-7)
      M ET-3 inhibited the peak of [Ca2+]i by 18 +/- 6% (n = 6, P = 0.02). 4. The anti
      aggregating agents, prostacyclin (PGI2, 10(-8)-10(-7) M) and nitroprusside (NP,
      10 ng-50 micrograms l-1) also induced a dose-dependent inhibition of the thrombin
      induced [Ca2+]i peak (P = 0.001 for each).A combination of 10-9M PGI2 and 1O ng
      P' NP augmented the inhibitory effect of each drug(PGI2 alone 52 +/-11, plus NP
      90 +/- 2; NP alone 26 +/- 4, plus PGI2 69 +/- 5% inhibition of [Ca2 ], peak, n =
      6 for each, P <0.01 and P <0.001, respectively). Platelet preincubation with 5 x
      10-7M ET-3 increased by 34+/-11% (n = 6, P = 0.0 14) the inhibitory effect of NP
      1O ng without a significant influence on the PGI2 effect.5. In conclusion,
      endothelins ET-1 and ET-3 can reduce in vitro the aggregating response of human
      platelets to thrombin by a mechanism that is probably due to decrease Ca2+
      mobilization.

PMID- 1393298
TI  - Proceedings of the British Pharmacological Society Meeting. Dublin, 8-10 July
      1992. Abstracts.

PMID- 1393295
TI  - Mode of action and comparative efficacy of pharmacological agents that inhibit
      calcium-dependent dehydration of sickle cells.
AB  - 1. Selected Ca-channel antagonists were tested at 20 microM as inhibitors of
      Ca(2+)-uptake in human sickle red cells. Nitrendipine, fendiline, and bepridil
      (and its stereoisomers), were found to be as effective as methoxyverapamil (D
      600) in inhibiting a fraction (25%) of Ca(2+)-uptake. In contrast cetiedil and
      Org 30701 were ineffective. 2. The drugs were subsequently tested as inhibitors
      of Ca(2+)-induced K+ efflux (Gardos) from sickle cells. They all showed
      inhibitory activity, with the order of efficacy nitrendipine greater than
      fendiline greater than bepridil greater than cetiedil greater than Org 30701. 3.
      With a 15 h programme of deoxygenation/reoxygenation cycles in a gas exchanger,
      it was shown that the inhibitors protected against cellular dehydration and loss
      of filterability in the order nitrendipine greater than fendiline greater than
      bepridil greater than cetiedil greater than Org 30701. However, significant
      stomatocytosis occurred at high concentrations of cetiedil, and bepridil
      (including its stereoisomers and analogues) impairing cell deformability. 4. It
      is concluded that Ca-antagonists may partially block both Ca(2+)-uptake and
      Ca(2+)-induced K+ efflux. The latter pathway is significant in contributing to
      sickle cell dehydration and nitrendipine is the most effective inhibitor of this
      route.

PMID- 1393297
TI  - Classification of platelet and vascular prostaglandin D2 (DP) receptors:
      estimation of affinities and relative efficacies for a series of novel bicyclic
      ligands. With an appendix on goodness-of-fit analyses.
AB  - 1. The DP receptors located on platelets and vasculature were examined in a human
      washed platelet preparation and in isolated rings of rabbit external jugular
      vein. 2. A series of eight novel bicyclic compounds were studied for their
      effects in the two assays. Seven produced agonism, inhibition of aggregation or
      vascular relaxation, and one compound was 'silent' in both assays. 3. The
      operational model of agonism (Black & Leff, 1983) was fitted simultaneously to
      concentration-effect curve data for the seven agonist compounds. The affinity and
      efficacy estimates so obtained were tested for similarity between the two tissues
      by analysis of variance, showing that the model could be fitted to both sets of
      data by assuming the same relative affinity and efficacy values. However,
      absolute affinity estimates were consistently lower in the vascular preparation.
      4. Analysis of two of the seven agonists as antagonists was also possible. This
      provided pKB estimates which supported the agonist affinity estimates. The eighth
      compound was also analysed as an antagonist. It, like the other seven,
      demonstrated a difference in affinity between the two tissues. 5. The results of
      this study support the view that platelet and vascular DP receptors are similar,
      assuming that the systematic difference in affinity estimates for the series of
      compounds between the two tissues is the consequence of receptor micro
      environment and/or accessory binding site differences.

PMID- 1393296
TI  - Adenosine-induced bronchoconstriction of isolated lung and trachea from
      sensitized guinea-pigs.
AB  - 1. The bronchoconstriction of airway-perfused lungs and contraction of superfused
      tracheal spirals from guinea-pigs in response to adenosine were examined. 2. In
      lungs from untreated animals, adenosine had little effect unless the perfusion
      pressure was raised with carbachol (1.1 microM), when it caused a fall in
      perfusion pressure. However, if removed from guinea-pigs sensitized with
      ovalbumin (5 mg and 10 mg i.p. 14 and 12 days before use), adenosine was
      bronchoconstrictor, exerting bronchodilator effects only at high (1 mg) doses.
      The constrictor response to adenosine (300 micrograms) was significantly greater
      than that in lungs from untreated or sham-injected animals. 3. In superfused
      trachea from untreated animals, adenosine exerted only relaxant responses. In
      tissues from ovalbumin-sensitized guinea-pigs adenosine produced contractile
      responses, with relaxation appearing only at high (1 mg) doses. 4. Thus
      sensitization by antigen challenge revealed a bronchoconstrictor response of
      isolated airway preparations to adenosine. This is related to the clinical
      situation where only asthmatic subjects respond to adenosine by
      bronchoconstriction and suggests that the sensitization may destabilize
      inflammatory cells for mediator release by adenosine. 5. The response to a second
      exposure to adenosine was consistently reduced (lungs) or converted to a
      relaxation (trachea) indicating tachyphylaxis and consistent with a mediator
      release mechanism. 6. The P1-purinoceptor antagonist, 8-phenyltheophylline (3.9
      microM), antagonized the relaxant responses to higher doses of adenosine.
      However, it did not affect the contractile responses to lower doses of adenosine.
      Whether this is due to P,-purinoceptors not being involved in the contractile
      response, or whether preferential blockade of the relaxant response leaves the
      contraction unopposed and apparently unblocked, remains to be established.

PMID- 1393299
TI  - Phenomenology. Its place in schizophrenia research.

PMID- 1393300
TI  - The origins of delusion.
AB  - Although delusion remains one of the basic problems in psychopathology, attempts
      to understand its pathogenesis have been dominated by unsubstantiated
      speculation. Previous psychodynamic formulations have recently given way to
      increasing interest in measurement, and testing of models derived from cognitive
      psychology. However, the formation, elaboration, and persistence of delusional
      beliefs may be an expression of the convergence of numerous causal influences,
      each exerting an effect at a different stage in the evolution of the belief. This
      review takes a structured overview of the literature, placing the numerous part
      theories and scant experimental findings within a general model of delusional
      development. It argues for a return to systematic research on symptoms rather
      than complex diagnostic formulations to facilitate better understanding of the
      development of delusional disorders and stimulate further interest in therapeutic
      intervention.

PMID- 1393301
TI  - Maintenance treatment in recurrent depression: current and future directions. The
      first William Sargant Lecture.

PMID- 1393303
TI  - Assessment of DSM-III-R personality disorders by self-report questionnaire: the
      role of informants and a screening test for co-morbid personality disorders
      (STCPD)
AB  - A modified version of the revised Personality Diagnostic Questionnaire (PDQ-R),
      based on DSM-III-R personality disorders (PDs), was completed by 60 psychiatric
      patients. An informant's version was also completed by 60 relatives or friends
      nominated by each subject. Discrete DSM-III-R PDs were rare; the mean number of
      PDs per subject was 4.5. Cluster analysis showed that only antisocial PD was a
      basis for classification of patients, while most patients formed two groups which
      were mainly distinguished by quantitative differences related to the total scores
      of positive PD criteria. A shorter version of the questionnaire can be used as a
      screening test for co-morbid PDs (STCPD) which can predict the number of co
      morbid DSM-III-R PDs. The total scores of positive PD criteria from the STCPD
      were usually (and significantly) higher than the corresponding scores from
      informants' questionnaires, but when an informant's total score exceeded that of
      the patient, this indicated a subject's under-reporting.

PMID- 1393302
TI  - Chromosomal aberrations and schizophrenia. Autosomes.
AB  - Chromosomal aberrations associated with schizophrenic disorders may suggest
      regions in which to focus a search for genes predisposing to schizophrenia by a
      linkage strategy. As for other genetic illnesses, chromosomal abnormalities may
      also provide useful tools for subsequent physical mapping, fine localisation, and
      isolation of important susceptibility genes. Identification of several
      chromosomal aberrations may be especially important, given the unknown
      pathophysiology, the paucity of known brain genes, and the probable genetic
      heterogeneity of schizophrenia and manic-depression. However, because psychiatric
      disorders are common and inherited in a complex manner, researchers must use
      caution when drawing inferences about associations with chromosomal aberrations.
      Reported abnormalities involving autosomes (chromosomes 1-22) associated with
      psychotic disorders are reviewed. Their relevance to linkage studies localising
      genes for schizophrenia was estimated by standardised criteria for specificity,
      diagnosis, family history, and overall weight of evidence. Four 'possibly
      relevant' chromosomal regions were identified: 5q, 11q, 18q, and 19p. This paper
      outlines strategies for future studies to detect new chromosomal aberrations
      associated with major psychotic disorders that may be relevant to isolating the
      genes for schizophrenia.

PMID- 1393304
TI  - Pharmacotherapy of social phobia. A controlled study with moclobemide and
      phenelzine.
AB  - In a double-blind, parallel group trial, 78 subjects with social phobia received
      moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or
      placebo. After eight weeks, both active drugs-phenelzine somewhat more than
      moclobemide--were clinically and statistically significantly more effective than
      placebo, as assessed by rating scales. There was some further improvement between
      weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the
      moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic.
      Moclobemide was, however, much better tolerated than phenelzine. Patients
      withdrawn from active drugs had relapsed by week 24, providing additional support
      for the efficacy of the active drugs.

PMID- 1393305
TI  - Plasma melatonin levels in anorexia nervosa.
AB  - Plasma melatonin levels were measured at three-hourly intervals over 24 hours in
      11 women with untreated anorexia nervosa, and in nine healthy women of normal
      weight. The circadian rhythm was unaltered but the nocturnal secretion of
      melatonin was significantly greater in anorectics. It is possible that this was
      related to nocturnal hypoglycaemia.

PMID- 1393306
TI  - Suicide and self-burning among Indians and West Indians in England and Wales.
AB  - Suicide levels in England and Wales during 1979-83 were low among males from the
      Indian subcontinent (SMR 73) and significantly high in young Indian women (age
      specific ratios 273 and 160 at ages 15-24 and 25-34 respectively). Suicide levels
      were low in Caribbeans (SMRs 81 and 62 in men and women respectively) and high in
      East Africans (SMRs 128 and 148 in men and women respectively). The excess in
      East Africans (most of whom are of Indian origin) was largely confined to younger
      ages. Immigrant groups had significantly higher rates of suicide by burning, with
      a ninefold excess among women of Indian origin. The pressures leading to higher
      suicide levels among young women of Indian origin highlight the need for making
      appropriate forms of support and counselling available to this community.

PMID- 1393307
TI  - Hysterical conversion. I: A history.
AB  - 'Hysterical conversion' dates from a century before Freud, from an important
      attempt to rationalise the nosological status of hysteria. Freud's own concept of
      'conversion' followed as a quite independent synthesis of 19th-century medical
      thinking on the subject. Subsequent analytical usage of 'conversion' which has
      influenced the description of hysterical syndromes within mainstream psychiatry,
      has not been consistent with Freud's own.

PMID- 1393308
TI  - Hysterical conversion. II: A critique.
AB  - The career of the diagnosis of conversion hysteria is reviewed at a time when it
      is threatened with expulsion from classifications of psychiatric disorder.
      Criticism of its face validity has not led to adequate diagnostic alternatives,
      and has been insensitive to its unusual form as a category as well as the
      contribution it has made to the stability of the classificatory system around it.

PMID- 1393309
TI  - Prenatal exposure to influenza does not cause schizophrenia.
AB  - Claims have been made that maternal infection with influenza during pregnancy is
      a cause of schizophrenia in the child. These assertions are based upon some
      apparently significant associations between the timing of influenza epidemics in
      the general population and birth rates of people who later suffered from
      schizophrenia. Such associations have not been present in studies of the 1919 and
      1957 epidemics, with sample sizes larger than those on which the claims were
      made. More decisively, in an investigation of the subsequent psychiatric
      admissions of people born a few months after the 1957 epidemic, it was found that
      the children of 945 mothers who actually suffered from influenza during the
      second trimester of pregnancy were at no greater risk of developing schizophrenia
      than children of mothers who were not infected. In contrast to the predictions of
      the influenza hypothesis of 26.5 extra cases by broad diagnostic criteria and
      15.8 cases by narrow criteria, the numbers observed in children of mothers
      exposed to influenza in the second trimester were 3 and 1 cases respectively,
      close to the expected rate. It is concluded that prenatal influenza and
      schizophrenia are unrelated.

PMID- 1393310
TI  - Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic.
AB  - "The birth dates of schizophrenic inpatients in eight health regions in England
      and Wales were reviewed for any effect of the 1957 A2 influenza epidemic. 5
      months after the peak infection prevalence, the number of births of individuals
      who later developed schizophrenia was 88% higher than the average number of such
      births in the corresponding periods of the 2 previous and the next 2 years. This
      finding is in accordance with a study from Helsinki and with clinical and
      neuropathological evidence of aberrant fetal brain development in the
      pathogenesis of schizophrenia."

PMID- 1393311
TI  - Failure of a binaural comprehension deficit to select responders to earplug use
      in schizophrenia.
AB  - Previous studies have suggested that on the Auditory Comprehension Test, a
      significant proportion of schizophrenics demonstrate a binaural comprehension
      deficit. To test whether wearing an earplug in their more poorly performing ear
      would be beneficial, we studied 34 in-patient schizophrenics and noted a binaural
      deficit in 12 (35%). Of these, eight patients subsequently wore an earplug in
      each ear for at least one week. We found no effect of the earplug on
      psychopathology.

PMID- 1393312
TI  - REM latency in endogenously depressed adolescents.
AB  - Twenty-three adolescents with DSM-III major depressive disorder (endogenous
      subtype) and 23 normal controls were studied polysomnographically (PSG). The
      depressed group showed significantly shortened REM latencies (P = 0.005) and
      longer sleep latencies (P = 0.04). No other PSG measures differentiated the two
      groups. The implications of these findings for adolescent depression are
      discussed.

PMID- 1393313
TI  - Psychotic illness following 'mabi bark tea' consumption.
AB  - A first episode of psychosis occurred in a young woman of West Indian parentage
      and one of identical twins following a brief period of high consumption of a
      drink made from Colubrina plant extract (mabi bark). The course of the psychosis
      is described and possible underlying mechanisms and the relationship to
      amphetamine psychosis are discussed.

PMID- 1393314
TI  - Charles Bonnet syndrome.

PMID- 1393315
TI  - Delusional infestation associated with post-herpetic neuralgia and EEG
      abnormalities.
AB  - An 80-year-old widow with delusional infestation in association with post
      herpetic neuralgia and EEG abnormalities in the left anterior parietal lobe
      responded to combined pimozide and carbamazepine. Aetiological factors are
      reviewed in relation to the literature.

PMID- 1393316
TI  - Severe deprivation in childhood: a case report from Thailand.
AB  - A 3 1/2-year-old girl was incarcerated in a bamboo cage after it was feared she
      had contracted rabies. Six years later, when she was released, she had lost
      almost all motor control, displayed a number of stereotypies, was incontinent of
      both faeces and urine, and was diagnosed as having grand mal epilepsy. After four
      years of treatment (aged 13) she had shown considerable improvement and her
      mental age was seven years.

PMID- 1393317
TI  - Multiple personality disorder.

PMID- 1393318
TI  - Multiple personality disorder.

PMID- 1393319
TI  - Multiple personality disorder.

PMID- 1393320
TI  - Preconscious perceptual processing.

PMID- 1393321
TI  - Reconquest of the subjective.

PMID- 1393322
TI  - Guilt or morbid remorse?

PMID- 1393323
TI  - Availability of the hospital anxiety and depression (HAD) scale.

PMID- 1393324
TI  - Hemispheric imbalance in schizophrenia.

PMID- 1393325
TI  - Applicability of psychotherapy for non-Western people.

PMID- 1393326
TI  - Psychological outcome of abortion.

PMID- 1393327
TI  - 'Socrates' symptom'.

PMID- 1393328
TI  - Clozapine in the community.

PMID- 1393329
TI  - ECT anaesthetics.

PMID- 1393331
TI  - Supervision of repeat antidepressant prescribing in general practice.

PMID- 1393330
TI  - Out-patient ECT for depression in a man with moderate learning disability.

PMID- 1393332
TI  - Personality disorder and self-wounding.
AB  - At least 1 in 600 adults wound themselves sufficiently to need hospital
      treatment. More men than women do it, although more women receive psychological
      treatment. Many have a history of sexual or physical abuse. Self-wounding differs
      from other self-harm in being aimed neither at mutilation nor at death. Self
      wounding coerces others and relieves personal distress. Repeated self-wounding is
      one criterion of borderline personality disorder but we prefer to consider it an
      'addictive' behaviour rather than an expression of a wider disorder.
      Psychological management may need to be augmented by drug or social treatment.
      Carers, including professional carers, usually need help to contain the
      turbulence that self-wounding produces.

PMID- 1393333
TI  - Child psychiatric disorders: are they classifiable?
AB  - Classification of child (including adolescent) disorders is reviewed within six
      areas: requirements for a good taxonomy, current systems of classification for
      children, data-capture methods, reliability and validity, the link between child
      and adult disorders, and directions for future developments. While substantial
      progress has been made, there is a continuing need for comparisons of different
      systems, more systematic yet practicable data capture, proper psychometric
      analyses of criteria and categories, intensive studies of clinical validity,
      closer attention to the similarity of, and links between, child and adult
      categories, and better definition and targeting of those disorders with a serious
      outcome.

PMID- 1393334
TI  - Presymptomatic testing for Huntington's disease in Wales 1987-90.
AB  - Between 1987 and 1990 a large series of at-risk individuals has been referred to
      our Huntington's disease (HD) presymptomatic testing programme. A detailed
      protocol for assessment and counselling has been followed. Out of 238 serious
      inquiries, 36% were potentially suitable for the testing programme, but 19% chose
      not to continue. Reasons for exclusion included the presence of clinical features
      of HD and being under the age of 18 years. Out of 40 final results given to 38
      individuals, 23 indicated a lowered risk, 11 an increased risk, while five
      results were uninformative, two of these becoming informative on repeat testing.
      This series contained more women than men, and was disproportionately from the
      higher socio-economic groups. Motives for requesting a test principally related
      to child-bearing, informing existing children, and planning for the future. No
      significant psychiatric symptoms have been reported in the short term, but
      difficult counselling problems were presented by the high proportion of
      applicants who already showed clinical signs of HD. It is concluded that a
      detailed counselling protocol is essential in testing for HD, as many applicants
      are ill-prepared; this will assume even greater importance when the HD gene is
      identified and a test for specific mutations is available. The experience of
      presymptomatic testing for HD provides important general lessons which are likely
      to be applicable to other inherited neurological and psychiatric disorders.

PMID- 1393335
TI  - The Scottish first episode schizophrenia study. VIII. Five-year follow-up:
      clinical and psychosocial findings. The Scottish Schizophrenia Research Group.
AB  - Forty-four schizophrenic patients were followed up for five years after their
      first admission to hospital for a first episode of illness. Thirteen (30%) of 43
      patients had not relapsed; 28 of the 30 patients who did relapse did so within
      the first 42 months. The relapses occurred despite antipsychotic drug therapy.
      Also, 24% of patients had at least one course of ECT. Only 19% of the patients at
      five years were in open employment; unemployment was strongly associated with
      relapse. Eighteen per cent had neither relapses nor schizophrenic symptoms at
      follow-up. Poor outcome at five years was associated with greater psychological
      distress among relatives at first admission. At five years 43% of relatives
      continued to show case level psychological stress.

PMID- 1393336
TI  - Dangerous behaviour preceding first admissions for schizophrenia.
AB  - Of 253 patients in their first schizophrenic episode, 52 behaved in a way
      threatening to the lives of others before their admission to hospital. These 52
      patients were studied from data collected at the time of their initial
      presentation. Despite a history of illness in excess of 1 year in 24 cases, and
      evidence that violence was motivated by psychotic symptoms in 23 cases, fewer
      than half of the patients were admitted to hospital as a direct result of their
      dangerous behaviour. Life-threatening behaviour was more common where the patient
      had been ill for longer, and where there were delusions of being poisoned.

PMID- 1393337
TI  - Seasonality of admissions in the psychoses: effect of diagnosis, sex, and age at
      onset.
AB  - A summer peak was found in first admissions to hospitals in England and Wales
      between 1976 and 1986 for both affective psychoses and schizophrenia, but not for
      neurotic conditions or personality disorders. There was no significant
      relationship between age at first admission and season of admission. The summer
      peak was most prominent for mania, where it was present in both sexes; for
      schizophrenia, it was present only in females. These findings suggest that
      schizophrenia in females, and mania in both sexes, have some aetiological or
      precipitating factor in common.

PMID- 1393338
TI  - Diurnal rhythms and symptom severity in panic disorder. A preliminary study of 24
      hour changes in panic attacks, generalised anxiety, and avoidance behaviour.
AB  - Diurnal changes in the frequency of panic attacks and symptoms of generalised
      anxiety, phobic anxiety and phobic avoidance in 34 panic-disorder patients and 40
      normal controls were evaluated. The panic-disorder patients had significant
      diurnal changes in generalised and phobic anxiety, but not phobic avoidance.
      Increased severity of symptoms and prominent diurnal changes were most evident in
      the panic-disorder patients with a history of depression. Although panic attacks
      were distributed throughout the 24-hour period, patients with a current episode
      or history of depression tended to have more frequent panic attacks in the
      morning or early afternoon. These observations challenge the traditional belief
      that 'anxious neurotic' patients are relatively asymptomatic upon awakening in
      the morning and then develop more severe symptoms of anxiety later in the day.

PMID- 1393339
TI  - Cortisol and prolactin responses to d-fenfluramine in non-depressed patients with
      obsessive-compulsive disorder: a comparison with depressed and healthy controls.
AB  - Cortisol and prolactin responses to d-fenfluramine were measured in 10 drug-free
      normothymic patients with obsessive-compulsive disorder (OCD). The results were
      compared with these responses in 10 healthy controls and in 10 major depressives.
      The endocrine responses in OCD were significantly attenuated when compared to the
      healthy controls; however, the results were not specific to OCD as the
      depressives' responses were similarly blunted.

PMID- 1393341
TI  - The role of the amygdaloid complex in Gilles de la Tourette's syndrome.

PMID- 1393340
TI  - The Edinburgh cohort of HIV-positive drug users: pattern of cognitive impairment
      in relation to progression of disease.
AB  - To examine the neuropsychiatric effects of infection with HIV, 220 drug users (27
      HIV negative, 193 HIV positive) completed tests evaluating premorbid
      intelligence, memory, non-verbal performance, information processing speed, and
      mood. When these measures were compared cross-sectionally by the severity of HIV
      illness, symptomatic patients (in CDC stage IV) were impaired on Trails B, two
      choice decision time, delayed recall of the Wechsler Logical Memory Test and most
      components of the Auditory Verbal Learning Test. These findings imply reduced
      capacity for concentration, speed of thought and memory. When 101 patients were
      retested a mean of 16 months after their initial assessment, performance on
      Trails A and B, Block Design and delayed recall of the Wechsler Logical Memory
      Test deteriorated more for patients at, or progressing within, CDC stage IV, than
      performance of patients at stage III. The results broadly correspond to the cross
      sectional findings. However, there was a decline in all tests of memory function
      for the sample independent of clinical staging. This may be evidence of brain
      involvement before the appearance of other symptoms. Self-rated measures of mood
      did not change cross-sectionally, progressively, or interactively with time and
      stage of HIV illness, and cannot account for the changes in cognitive function
      observed. Change in drug use, similarly, does not account for the cognitive
      findings. Four (5%) of the retested subjects developed AIDS dementia complex, but
      most of the performance and memory impairments seen were subclinical despite the
      destructive neuropathology presumed to underlie intellectual decline in patients
      with HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393342
TI  - Stressful life events and Graves' disease.
AB  - "The role of stressful life events in the onset of Graves' disease (toxic diffuse
      goitre) is controversial. However, the numerous early clinical reports that
      supported such an association were not adequately controlled and specificity of
      the diagnosis could be questioned. Later studies have not shown a causal
      relation, but these studies were small, did not have proper controls, or
      epidemiological methods were inappropriate. To assess possible associations
      between life events, heredity, social support, and Graves' disease, we have done
      a population-based case-control study in a defined area with about 1 million
      inhabitants. Over 2 years, 208 (95%) of 219 eligible patients with newly
      diagnosed Graves' disease and 372 (80%) of all selected matched controls answered
      an identical mailed questionnaire about marital status, occupation, drinking and
      smoking habits, physical activity, familial occurrence of thyroid disease, life
      events, social support, and personality. Compared with controls, patients claimed
      to have had more negative life events in the 12 months preceding the diagnosis,
      and negative life-event scores were also significantly higher (odds ratio 6.3,
      95% confidence interval 2.7-14.7, for the category with the highest negative
      score). Individuals who had relatives with thyroid disease (especially first
      degree and second-degree relatives) were more likely to have Graves' disease
      (3.6, 2.2-5.9). Slightly more patients than controls were divorced (1.8, 1.0-3.3)
      and reported a less frequent intake of alcohol (0.4, 0.2-0.8). When results were
      adjusted for possible confounding factors in multivariate analyses, risk
      estimates were almost unchanged. These findings indicate that negative life
      events and hereditary factors may be risk factors for Graves' disease."

PMID- 1393343
TI  - Mental play in Gilles de la Tourette's syndrome and obsessive-compulsive
      disorder.
AB  - A new phenomenon, found only in Gilles de la Tourette (GTS) patients, and which
      we have called 'mental play', is described. It was compared with the phenomenon
      of counting, which occurred in both GTS and obsessive-compulsive patients. In the
      GTS patients both mental play and counting were best characterised as playful
      impulsions. In contrast to the GTS patients, the counting of the obsessive
      compulsive patients was in line with their obsessive-compulsive behaviour. These
      findings suggest that repetitive symptoms in GTS patients, even when they share
      superficial similarities with obsessive-compulsive symptoms, should not be
      diagnosed automatically as obsessive-compulsive.

PMID- 1393344
TI  - Bulimia nervosa in Hong Kong Chinese patients.
AB  - In contrast to the West, bulimic disorders are rarer than anorexia nervosa in
      Hong Kong. Four female normal-weight bulimic patients with mostly typical
      clinical features and conspicuous morbidity are reported. The case histories
      support the hypothesis that binge-eating is used to regulate unpleasant effect.

PMID- 1393345
TI  - Chromosomal aberrations in a patient with severe psychopathology.
AB  - The case of a female patient showing aggressive, compulsive, destructive
      behaviour, ritualistic faecal smearing, and hyperactivity is presented. The
      behaviour is long standing, therapy-resistant, and its aetiology is unknown,
      although it is seemingly associated with chromosomal abnormalities secondary to
      abnormal plasma factors.

PMID- 1393346
TI  - Lower incidence and increased male:female ratio in schizophrenia.
AB  - Patients with an ICD-9 diagnosis of psychotic disorder were assessed for DSM-III
      R schizophrenia. Rates of schizophrenia were found to be higher in males (39.8
      per 100,000) than females (22.4 per 100,000). The DSM-III-R incidence supports
      recent studies which suggest a decrease in rates of schizophrenia across time,
      and also suggests that men suffer from both more schizophrenia and a more severe
      form of the disease.

PMID- 1393348
TI  - Carbamazepine-induced systemic lupus erythematosus.
AB  - A 21-year-old woman suffering from bipolar affective disorder developed systemic
      lupus erythematosus (SLE) with characteristic laboratory findings, 18 months
      after starting carbamazepine maintenance treatment. SLE receded after withdrawal
      of carbamazepine and treatment with anti-inflammatory drugs. Although both the
      spontaneous occurrence of SLE and the psychosis as a sign of CNS involvement of
      SLE cannot be excluded, SLE could be considered as an adverse effect of
      carbamazepine.

PMID- 1393347
TI  - Catatonia and the neuroleptic malignant syndrome--a single entity?
AB  - Separate episodes of both catatonia and the so-called 'neuroleptic malignant
      syndrome' (NMS) occurred within the same patient. The only evidence for NMS in
      this case was prior administration of a neuroleptic and the presence of
      generalised muscular rigidity. It is suggested that it is misleading to view
      these conditions as separate diagnostic entities and that NMS is probably more
      correctly incorporated into the catatonic disorders.

PMID- 1393349
TI  - Deja vu experiences and reduplicative paramnesia.
AB  - A schizophrenic patient with different forms of experiences of inappropriate
      familiarity is described. The authors discuss traumatic experiences as
      aetiological factors in deja vu experiences and reduplicative paramnesia.
      Finally, the differential diagnostic problem in psychotic and dissociative
      phenomena is stressed.

PMID- 1393350
TI  - X-linked bipolar illness.

PMID- 1393352
TI  - Preconscious perceptual processing.

PMID- 1393351
TI  - Maternal viral infection hypothesis.

PMID- 1393353
TI  - Rapid tranquillisation.

PMID- 1393354
TI  - 'Suicide prevention' by GPs?

PMID- 1393355
TI  - The cultural specificity of psychotherapy.

PMID- 1393356
TI  - Effect of ECT on insulin.

PMID- 1393358
TI  - Evaluation in mental health care.

PMID- 1393357
TI  - Reliability of DISCUS rating in individuals with learning disabilities.

PMID- 1393359
TI  - Hypnotising lobsters, etc.

PMID- 1393360
TI  - Reporting predictable negative results.

PMID- 1393361
TI  - Koro and Capgras syndrome in a non-Chinese subject.

PMID- 1393362
TI  - Postnatal depression and antenatal morbidity.

PMID- 1393363
TI  - Dimensions of everyday memory in young adulthood.
AB  - This paper reports the findings of two studies on everyday memory in young
      adulthood. In Study 1, 387 male and female college students (18-22 years old)
      completed the 25-item Cognitive Failures Questionnaire (CFQ; Broadbent, Cooper,
      Fitzgerald & Parkes, 1982). Principal components analysis yielded five internally
      consistent factors: distractibility; misdirected actions; spatial/kinaesthetic
      memory; interpersonal intelligence; and memory for names. Further, each of these
      dimensions was interpretable within an information-processing framework. Study 2
      examined the relation of the five everyday memory dimensions obtained in Study 1
      to measures of working memory and traditional intelligence in a separate sample
      of 32 college students. Findings obtained in Study 2 suggest that attentional
      processes may be important components of the everyday memory construct.

PMID- 1393364
TI  - The effect of a five-month delay on children's and adults' eyewitness memory.
AB  - Child witnesses must endure a delay of around six months between observing or
      being the victim of an alleged offence and being required to give evidence in a
      criminal court. While the legal profession seem to believe that young children's
      memories are particularly sensitive to the passage of time, developmental
      psychology can offer little relevant data to support or refute this presumption.
      In the present study, children aged six and nine years and adults witnessed a
      staged event and were subsequently interviewed in the days following the event
      and/or five months later. Results indicate that while all witnesses forgot
      information over this period, the younger children (six years) recalled slightly
      less information than the older children and the adults. The total amount of
      incorrect information recalled did not increase over the same period. Two
      different interviewing techniques were used--cued recall vs. 'enhanced' recall-
      the latter incorporating some aspects of the cognitive interview procedure. No
      differences were found relating to the interview techniques employed. The results
      underline the importance of recording initial interviews with child witnesses
      wherever possible.

PMID- 1393365
TI  - Expedition stress and personality change.
AB  - There have been few attempts to investigate the widespread assumption that short
      term challenges can have beneficial effects on personality. An expedition to
      India organized by the British Schools Exploring Society provided such an
      opportunity. The Gordon Personal Profile Inventory showed that the expedition was
      associated with increased ascendancy, emotional stability, sociability and
      responsibility, and decreased cautiousness. Women tended to benefit more than
      men. The results suggest that the expedition was associated with positive
      personality changes, though other explanations of the findings cannot be ruled
      out.

PMID- 1393366
TI  - Short-term retention of spatial information.
AB  - Four experiments investigated the recall of a subspan set of spatial locations
      over short intervals of 5 and 15 s. The intervals were filled by one of three
      activities: simple tapping, repeated tapping at spatial targets and backwards
      counting. Spatial tapping, which decreases spatial memory span, led to further
      small but significant errors in recall, as did backward counting. These errors
      were larger than those found with simple tapping over the same intervals.
      Backwards counting led to further decreases in recall performance if it was also
      present during encoding, but this was not the case for spatial tapping. Spatial
      tapping had little effect on recall of three digits, whereas backwards counting
      had a large effect, which was much larger than that found with spatial memory
      items in any condition. The results are interpreted in terms of the use of place
      keeping functions in spatial memory sequences, which may not be specific to
      spatial material.

PMID- 1393368
TI  - What research should the Arthritis and Rheumatism Council be funding?

PMID- 1393367
TI  - Phonological priming of lexical retrieval in speech production.
AB  - We report a series of three experiments exploring phonological priming effects in
      speech production. In all cases, subjects repeated aloud auditorily presented
      primes and then named picture targets. Experiment 1 showed that targets were
      named faster when prime and target shared phonemes but only when these occupied
      the same word or syllabic positions. Experiment 2 showed that the degree of
      facilitation was unaffected by the lexicality of the prime or whether shared
      phonemes occurred early or late in the syllable. Experiment 3 examined the effect
      of the lexicality of the prime at different intervals between response and prime
      in an attempt to tease apart contributions to the effect from automatic and
      strategic processes. The results are considered in relation to current accounts
      of lexical retrieval.

PMID- 1393369
TI  - Academic rheumatology and the Arthritis and Rheumatism Council.

PMID- 1393370
TI  - Detection of cytokines at the cartilage/pannus junction in patients with
      rheumatoid arthritis: implications for the role of cytokines in cartilage
      destruction and repair.
AB  - Cytokine release at the cartilage/pannus junction (CPJ) may be involved in
      cartilage destruction and tissue repair in rheumatoid arthritis (RA). Tissue
      samples of CPJ from 12 RA patients were examined for the presence of cytokines
      using immunohistochemical techniques with immunoaffinity purified F(ab')2
      antibodies raised against recombinant human cytokines. Twenty-four areas of
      distinct CPJ at which a discrete junction between cartilage and overlying pannus
      exists were observed. In all specimens, tumour necrosis factor (TNF)-alpha,
      interleukin (IL)-1 alpha. IL-6, granulocyte-macrophage colony-stimulating factor
      (GM-CSF) and transforming growth factor (TGF)-beta 1 were detected in cells in
      pannus particularly along the surface of cartilage and at the site of cartilage
      erosion. Double immunofluorescence staining showed that most cytokine containing
      cells also labelled with a macrophage marker (CD68). About 50% of blood vessel
      endothelial cells stained for GM-CSF. Twelve areas of diffuse fibroblastic CPJ,
      at which an indistinct margin is seen between cartilage and pannus were examined.
      At this site, TGF-beta 1 was the only cytokine detected in fibroblast-like cells.
      None of these cytokines were detected in synovial tissue at the normal
      synovium/cartilage junction. Chondrocytes from all 11 normal specimens as well as
      those from RA patients stained for IL-1 alpha, TNF-alpha, IL-6, GM-CSF and TGF
      beta 1, especially those close to subchondral bone. However, IL-1 beta,
      interferon-gamma and lymphotoxin were not detected in either the normal
      synovium/cartilage junction or rheumatoid CPJ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393371
TI  - Influence of steroid hormones on proliferation of peripheral blood mononuclear
      cells in patients with rheumatoid arthritis.
AB  - Sex steroids are believed to modulate the immune system in rheumatoid arthritis
      (RA). Since receptors for sex steroids are present on T-lymphocytes, which are
      thought to play a major role in the pathogenesis of RA, it is suggested that
      gonadal steroids can mediate their immunomodulating effect directly on T
      lymphocytes. Recently a specific method for activating T-lymphocytes with
      immobilized anti-CD3 monoclonal antibodies was described. We investigated the
      influence of oestradiol, progesterone, testosterone and cortisol on lymphocytes
      stimulated by anti-CD3 mAb and PHA of postmenopausal women, comparing female
      patients with rheumatoid arthritis and age-matched control patients. The results
      show that oestradiol, progesterone and testosterone do not influence lymphocyte
      proliferation when stimulated with anti-CD3 mAb or phytohaemagglutinin (PHA).
      Cortisol, however, can suppress lymphocyte proliferation even at physiological
      concentrations in both patients with RA and controls. Inhibition of proliferation
      by cortisol is dose-related and has no significant correlation with RA disease
      activity. This inhibition differs individually and might explain the often
      variable response to corticosteroids in vivo.

PMID- 1393372
TI  - Antilactoferrin antibody in systemic lupus erythematosus.
AB  - Lactoferrin is a secondary granule protein of neutrophils. Seventy-nine systemic
      lupus erythematosus patients who fulfilled the ARA criteria for classification
      were tested for antibody against human lactoferrin (LF-ab) by ELISA. Thirty-one
      of these (39.2%) demonstrated elevated levels. There was significant correlation
      between LF-ab positivity and disease duration. Clinical flare was common with
      positive LF-ab (P less than 0.05). Disease manifestations were independent of
      antibody status except for an increased incidence of lymphadenopathy and
      crescentic gomerulonephritis among those who had LF-ab. No consistent
      immunofluorescence pattern could be demonstrated on alcohol-fixed neutrophils for
      the LF-ab positive sera. It is suggested that LF-ab is related to lupus activity,
      and can be useful as a marker for disease monitoring.

PMID- 1393373
TI  - Increased spontaneous release of cytidine deaminase by polymorphonuclear
      neutrophils of patients with active systemic lupus erythematosus.
AB  - Cytidine deaminase activity (CD) in the neutrophil culture supernatants (PMN SUP)
      of 27 patients with systemic lupus erythematosus (SLE) was measured using a
      spectrophotometric method. Compared with the controls (5.449 +/- 1.358 U/5 x
      10(6) PMN), the CD activity in the spontaneous culture supernatants of PMN was
      significantly increased in active (10.003 +/- 2.637 U/5 x 10(6) PMN) but not in
      inactive (5.358 +/- 1.624 U/5 x 10(6) PMN) SLE. However, after stimulation with N
      formyl-methionyl-leucyl-phenylalanine (FMLP, 1 x 10(-7) M), the ratio of enzyme
      activity between stimulated and spontaneous PMN supernatants was decreased in
      active SLE (0.794 +/- 0.178) compared with normal controls (1.300 +/- 0.225). In
      contrast, the enzyme activity in the cytoplasm of either stimulated or non
      stimulated PMN was not different among these three groups. These results suggest
      that CD of PMN is releasable and can be enhanced by chemotactic factor
      stimulation in normal PMN. The increased spontaneous release of CD by active SLE
      PMN is one of the indicators for the disease activity in these patients.

PMID- 1393374
TI  - The prevalence of diagnosed systemic lupus erythematosus in whites and Indian
      Asian immigrants in Leicester city, UK.
AB  - The prevalence of diagnosed systemic lupus erythematosus (SLE) during 1989 in the
      adult Indian Asian and White populations of the city of Leicester has been
      determined. Fifty cases (19 Asian, 31 White) fulfilling the 1982 revised ARA
      criteria for SLE were identified from a population of 191,469 (37,684 Asian,
      153,785 White). Five different sources were used to ascertain cases. The overall
      prevalence of SLE in Whites was 20.2 per 100,000. Asians of both sexes had a
      significantly higher prevalence than Whites. Prevalence in males was 31.5 and 7.0
      per 100,000 in Asians and Whites respectively; in females the figures were 69.7
      and 31.7 per 100,000. Overall, lupus was 3.0 times more common in Asians than
      Whites. This is the first prevalence study of SLE in Indian Asians and suggests
      that, like the Black races and the Chinese, they have a greater frequency of SLE
      than Whites.

PMID- 1393375
TI  - Alpha interferon-2a (Roferon-A) in the treatment of diffuse cutaneous systemic
      sclerosis: a pilot study. UK Systemic Sclerosis Study Group.
AB  - Intramuscular alpha-interferon improved or stabilized skin score in 10/14 (71%)
      patients with diffuse cutaneous systemic sclerosis. In 64% of patients, their
      treating physicians rated it as having stabilized or improved the disease.
      However, it had no significant effect on grip strength, digital contractures,
      respiratory function or visceral involvement. Type I collagen synthesis was
      significantly reduced in fibroblasts cultured from clinically 'uninvolved' skin
      but not in those from lesional skin. Amino-terminal procollagen III peptides in
      the interferon treated group were not significantly reduced after 6 months of
      therapy but showed a trend towards stabilization and reduction compared to
      disease matched controls on no therapy.

PMID- 1393376
TI  - Bronchiectasis and rheumatoid disease: is there an association?
AB  - Rheumatoid arthritis is associated with a number of pleuropulmonary disorders. A
      retrospective study of the frequency of rheumatoid disease in patients with
      bronchiectasis and pulmonary fibrosis was performed. The results suggest that the
      frequency of bronchiectasis and rheumatoid disease is similar to that of the well
      established, but rare, association between pulmonary fibrosis and rheumatoid
      arthritis. We therefore suggest that bronchiectasis should be remembered as a
      pulmonary association of rheumatoid disease which occurs as commonly as pulmonary
      fibrosis.

PMID- 1393377
TI  - Mixed connective tissue disease--goodbye to all that.
AB  - Since it was first described mixed connective tissue disease (MCTD) has been the
      subject of much debate. In particular the question of whether it is a truly
      distinctive disease entity has been challenged. It seems clear that the original
      description of MCTD as a mild disorder, rarely affecting the lungs or kidneys and
      requiring small doses of corticosteroids only, is no longer tenable. In this
      review a historical analysis of the clinical and serological features is
      presented. It is suggested that the concept of MCTD as a distinct disease entity
      is better replaced by the term 'undifferentiated autoimmune rheumatic/connective
      tissue disorder'. Many of these patients will later 'convert' into scleroderma or
      lupus; some will remain undifferentiated.

PMID- 1393378
TI  - Immunogenetics of rheumatoid arthritis and the Arthritis and Rheumatism Council's
      National Repository.

PMID- 1393379
TI  - Clinically normal skin becomes sclerodermatous when transplanted into a
      sclerodermatous area.
AB  - A 56-year-old female with systemic sclerosis developed sclerodermatous change in
      clinically normal forearm skin 10 months after this was transplanted to the tip
      of her right index finger. This observation implicates local factors in the
      pathogenesis of the disease.

PMID- 1393380
TI  - Sensorineural hearing loss in juvenile chronic arthritis.
AB  - An 18-year-old female with pauciarticular juvenile chronic arthritis is described
      who has developed a profound bilateral sensorineural hearing loss. The
      association of sensorineural hearing loss with juvenile chronic arthritis has not
      been reported before.

PMID- 1393381
TI  - Mastocytosis and osteoporosis.

PMID- 1393382
TI  - Transdermal fungal implantation causing an infectious arthritis.

PMID- 1393383
TI  - Viruses and rheumatic disease.

PMID- 1393385
TI  - Amyloid arthropathy complicating myelomatosis: successful treatment with
      radiosynovectomy.

PMID- 1393384
TI  - Erythema multiforme after intradural injection of prednisolone acetate.

PMID- 1393386
TI  - Synovitis in polymyalgia rheumatica: an immunogenetic study.

PMID- 1393387
TI  - Distraction, choice and self-esteem effects on cognitive response facilitation.
AB  - From an integration of distraction-conflict theory and cognitive dissonance
      theory, it was hypothesized that distraction would increase, rather than disrupt,
      the proarguing of persons who had been given high choice to engage in discrepant
      behaviour, and would increase, rather than disrupt, the counterarguing of persons
      who had been given low choice to engage in such behaviour. Furthermore, it was
      expected that this cognitive response facilitation effect would more likely occur
      for persons high in self-esteem. The results supported the hypotheses and were
      interpreted as also confirming the notion that dissonance-related processes occur
      at the cognitive response level.

PMID- 1393388
TI  - Use of ultrasound in osteomyelitis.
AB  - The use of ultrasound in osteomyelitis has been studied in 25 patients clinically
      suspected of osteomyelitis. A sonographic diagnosis of osteomyelitis was made if
      fluid was present in direct contact with the bone, without intervening soft
      tissues. This was thought to represent an inflammatory exudate dissecting in a
      subperiosteal and/or extraperiosteal location. Ultrasonographically 15 patients
      were found to have osteomyelitis, proved either by surgical drainage or needle
      aspiration. Seven patients had soft-tissue abscesses, one had cellulitis and two
      patients had no abnormality.

PMID- 1393389
TI  - Direct and CT measurements of canals and foramina of the skull base.
AB  - This investigation is based on measurements of 60 macerated adult European skulls
      from the Alexander-Ecker Collection at the Anatomy Department of the University
      of Freiburg. Computer tomographical (CT) and anatomical measurements were
      compared to assess the accuracy of the CT representation of osseous structures.
      Nine structures were examined: the optic canal; the superior orbital fissure; the
      foramen rotundum; the foramen ovale; the foramen spinosum; the foramen Vesalii
      (venosum); the carotid canal; the internal auditory canal, and the hypoglossal
      canal. The results show a good and even excellent correlation if the cranial
      opening is approximately at a right angle to the scanline. For this reason, the
      results of the coronal examination of the internal auditory canal are less
      satisfactory, and the coronal and axial measurements of the hypoglossal canal
      show only a moderately good correlation.

PMID- 1393391
TI  - What is the clinical disadvantage of discarding old radiographs? Survey of
      patients not re-examined for a long time.
AB  - The clinical disadvantage of discarding old radiographs was evaluated in patients
      who had not been re-examined for more than 8 years after their last radiological
      examination, 38,772 in total. During the 1 year survey, 158 (0.41%) of them
      underwent re-examination after a long interval. Retrospective evaluation revealed
      that in only 12 patients (0.032%) were the old films useful. This survey
      suggested that the clinical risk of not referring to films more than 8 years old
      would be less than 0.049%. We consider this acceptable, and have formulated new
      guidelines of storage of films.

PMID- 1393390
TI  - Subluxation of the patella: evaluation of patellar articular cartilage with MR
      imaging.
AB  - In patients with subluxation of the patella, injury of the patellar articular
      cartilage is frequently observed, and correct evaluation of this cartilage injury
      is extremely important for the management of these patients. Magnetic Resonance
      (MR) studies were performed on 102 patellofemoral (PF) joints of 51 patients with
      subluxation of the patella and 20 PF joints of 10 healthy volunteers. In 77 of
      the 102 PF joints with subluxation, arthroscopy and/or operation were performed.
      MR images were obtained with spin-echo and FLASH sequences, and para-axial images
      were obtained. We retrospectively analysed the MR findings of the 77 joints with
      special attention to the surface and thickness of the cartilage, and classified
      them into four grades. These MR grades were compared with the grades on
      arthroscopy, and the following results were obtained: MR grade 0, normal
      cartilage (n = 27, sensitivity 90.9%, specificity 74.2%); MR grade 1, thickening
      of the cartilage (n = 24, sensitivity 50%, specificity 89.1%); MR grade 2,
      surface irregularity of the cartilage (n = 20, sensitivity 85%, specificity
      94.7%); MR grade 3, loss of the cartilage (n = 6, sensitivity 100%, specificity
      100%). Although the early changes observed by arthroscopy were underestimated
      from the MR images, MR imaging proved to be extremely useful for evaluating
      moderately or advanced patellar cartilage injury.

PMID- 1393392
TI  - Intracardiac metastases from germ cell tumours--an unusual but important site of
      metastasis.
AB  - Two cases of intracardiac deposits from testicular teratomas diagnosed by
      echocardiography and angiocardiography, respectively, are described. The
      importance of recognizing this as an uncommon site of metastasis from germ cell
      tumours is discussed.

PMID- 1393393
TI  - The radiology and terminology of cryptogenic organizing pneumonia.
AB  - The clinical features, radiographic and computed tomographic findings of nine
      patients with histological proof of cryptogenic organizing pneumonia were
      analysed. Patients present with cough, dyspnoea and malaise and commonly have
      bilateral multifocal consolidation on chest radiography, which may show
      resolution or relapse with or without steroid treatment. A good response to
      steroids is the rule, usually with complete radiological resolution or minimal
      residual scarring. The relative merits of the terms cryptogenic organizing
      pneumonia and bronchiolitis obliterans organizing pneumonia, both currently used
      to describe this entity, are discussed.

PMID- 1393394
TI  - The radiological imaging of bronchial atresia.
AB  - The clinical and radiological findings in three cases of bronchial atresia are
      presented. Bronchial atresia has a characteristic plain radiographic appearance
      in the majority of cases. Computed tomography may be required to confirm the
      diagnosis. The condition often presents to the radiologist as an incidental
      finding on the chest radiograph in a patient undergoing investigation for an
      unrelated problem.

PMID- 1393395
TI  - An alternative approach to contrast-detail testing of X-ray image intensifier
      systems.
AB  - The difficulties of making the results of threshold contrast-detail diameter
      tests on X-ray image intensifier systems consistent with published performance
      standards are discussed. The current approach to contrast-detail testing is
      described and an alternative method intended to give greater consistency for all
      image intensifier input field diameters proposed. The current and alternative
      test conditions are compared on two image intensifier systems. The results
      obtained show that the contrast-detail curves for image intensifier systems with
      a wide range of input field diameters can be effectively normalized to be
      directly comparable to a common reference standard by applying the proposed
      alternative test conditions. The implications of this result on the
      interpretation of the contrast-detail test are discussed.

PMID- 1393396
TI  - Accelerated fast neutron therapy: a pilot study.
AB  - The clinical role of fast neutron therapy has been limited by excessive late
      normal tissue damage. A pilot study of accelerated fractionation of fast neutron
      therapy was performed, based on the rationale that this should result in an
      increase in the response in acute reacting tissues (normal and malignant), with
      no change in late damage and a consequent increase in the therapeutic ratio.
      Further accelerated fractionation should improve the local control of rapidly
      proliferating tumour, without the potential problem of inadequate reoxygenation
      inherent in accelerated photon schedules. 6 or 12 fractions of 62 MeV (p-Be)
      neutrons were given over 12 days to 27 sites in 23 patients with locally advanced
      tumours. With a dose reduction of 12% (18 Gy), acceptable skin and oral mucosa
      early reactions were obtained. A larger dose reduction (15%) was required at
      pelvic sites. The incidence of late EORTC/RTOG grade 4 toxicity was 46%. The
      overall response rate was 76% with a complete response rate of 16%. For locally
      advanced breast cancer, the complete response rate was 9%, which compares
      unfavourably with previous results with conventional neutron fractionation
      schedules. The combination of a low overall complete response rate and excessive
      late normal tissue toxicity suggests that accelerated fractionation of fast
      neutrons does not lead to an improvement in the therapeutic ratio, and that late
      normal tissue damage will continue to be dose limiting.

PMID- 1393397
TI  - Low oxygen extraction fraction in tumours measured with the oxygen-15 steady
      state technique: effect of tissue heterogeneity.
AB  - Several reports have described decreased oxygen extraction fractions in tumours
      relative to those in normal tissues as measured with the oxygen-15 steady state
      technique and positron emission tomography. The present simulation study was
      carried out to assess the influence of tissue heterogeneity on these measured
      values. It was found that, within the range analyzed, tissue heterogeneity always
      resulted in underestimations of mean values of oxygen extraction fraction. It
      must, therefore, be concluded that the oxygen-15 steady state technique is not an
      accurate method for the assessment of the oxygen status of tumours. This finding
      should also apply to other pathological conditions, where a significant degree of
      tissue heterogeneity can not be excluded. More generally, this study demonstrates
      the need for detailed analyses of sensitivities of tracer kinetic procedures to
      tissue heterogeneity.

PMID- 1393398
TI  - Image comparison techniques for use with megavoltage imaging systems.
AB  - In this paper we describe software facilities for enabling patient positioning
      studies using the megavoltage imaging system developed at the Royal Marsden
      Hospital and Institute of Cancer Research. The study focuses on the use of the
      system for three purposes: patient position verification (by comparing images
      taken at treatment simulation with megavoltage images taken at treatment time);
      reproducibility studies (by analysing a set of megavoltage images); and set-up
      correction (by adjusting the set-up until the megavoltage image obtained at
      treatment registers with the simulation image). The need is discussed for
      suitably presented simulator images, a method of determining field boundaries and
      the possibility of delineating soft-tissue interfaces. Several algorithms of
      different types, developed specifically for the purpose of intercomparison of
      planar projection images, are presented. The techniques employed and their
      usefulness, in both the qualitative and the quantitative sense, are discussed.
      The results are presented of a phantom and clinical study, to evaluate the rigour
      and reproducibility of the algorithms. These results indicate that measurements
      can be made to an accuracy of about 1-2 mm, with a similar value for
      interobserver reproducibility for the best image comparison techniques available.

PMID- 1393399
TI  - Asymptomatic temporal lobe injury after radiotherapy for nasopharyngeal
      carcinoma: incidence and determinants.
AB  - Computed tomography (CT) scans were performed on a cohort of 60 patients for
      detection of temporal lobe injury (TLI) at 1-3.5 years after radiation therapy
      for nasopharyngeal carcinoma. Nine cases of TLI were identified, five of which
      were asymptomatic. The earliest case of asymptomatic TLI was found at 2.2 years
      after radiation therapy and the earliest symptomatic case at 2.3 years. A
      significantly higher incidence of TLI was found in patients with decreased
      temporal lobe shielding consequent to omitted eyeshield to the anterior photon
      beam and in patients treated with a hyperfractionation schedule giving 67.2 Gy in
      42 fractions in 6 weeks. The incidence in these subgroups at 2-3.5 years after
      radiation therapy was 56% (5/9 patients) and 35% (8/23 patients), respectively.
      No patient in this study had TLI in the absence of these two factors. The
      implications of the results are discussed.

PMID- 1393400
TI  - Anal endosonography: which endoprobe?

PMID- 1393401
TI  - Virtual source distances and field geometry independent output factors for 5-14
      MeV electron beams from a Siemens Mevatron M7145.

PMID- 1393402
TI  - Gadolinium-DTPA enhanced MRI in neonatal osteomyelitis of the cervical spine.

PMID- 1393403
TI  - Patellar metastasis: a rare presentation.

PMID- 1393404
TI  - Renal ultrasonographic appearances at presentation in an infant with Lesch-Nyhan
      syndrome.

PMID- 1393405
TI  - A rare cause of a common symptom.

PMID- 1393406
TI  - Spontaneous disappearance of staghorn calculus.

PMID- 1393407
TI  - Invited review: permanent radiation myelopathy.

PMID- 1393408
TI  - Primary choroid plexus papilloma of the cerebellopontine angle: magnetic
      resonance imaging, computed tomographic and angiographic appearances.
AB  - The computed tomographic, angiographic and magnetic resonance imaging (MRI)
      appearances of a benign primary choroid plexus papilloma of the cerebellopontine
      angle are reported. Although benign, this tumour showed local invasion of the
      petrous temporal bone and mastoid air cells. The differential diagnosis of
      cerebellopontine angle lesions is discussed. Papilloma is suggested by the
      presence of a vascular, calcified, enhancing extra-axial mass in or around the
      cerebellopontine angle. MRI may show evidence of high vascularity and internal
      haemorrhage. Differentiation from other cerebellopontine tumours, most
      particularly meningioma, may not be possible on radiological features.

PMID- 1393409
TI  - How frequent is chronic lumbar arachnoiditis following intrathecal Myodil?
AB  - Chronic lumbar arachnoiditis has numerous causes, including the introduction of
      contrast media into the lumbar subarachnoid space. The oily contrast medium
      Myodil (iophendylate) is often cited but the true incidence of symptomatic lumbar
      arachnoiditis due solely to the presence of Myodil is unknown. A retrospective
      review of 98 patients in whom Myodil was introduced by ventriculography or
      cisternography, i.e. remote from the lumbar spine, revealed no cases of chronic
      lumbar arachnoiditis. All patients were monitored closely for periods ranging
      from 1 to 28 years. We conclude that, in these circumstances, it is rare for
      Myodil to produce symptomatic arachnoiditis.

PMID- 1393410
TI  - The prognostic importance of CT features in primary intracranial lymphoma.
AB  - The correlation of computerized tomography (CT) features with survival of 28
      patients with primary intracranial lymphoma was analysed retrospectively. Severe
      perifocal oedema, periventricular tumours and lesions which were non-homogenously
      enhancing or non-enhancing were found to be associated with a poor prognosis. The
      prognosis when multiple lesions were present was almost the same as that of a
      solitary lesion (p = 0.95). Ring enhancing lesions had considerably longer
      survival. Lesions in the frontal region and those close to the meninges,
      enhancing homogeneously, had a better prognosis.

PMID- 1393411
TI  - Transverse geniculate ligament of the knee: appearance and frequency on plain
      radiographs.
AB  - The aims of the study were to determine the frequency of visualization of the
      normal transverse geniculate ligament (TGL) of the knee on lateral plain
      radiographs with magnetic resonance imaging (MRI) as a reference, and to
      determine features that make this ligament apparent on plain radiographs. 50
      consecutive lateral plain radiographs and sagittal T1-weighted images of
      corresponding knees were evaluated prospectively. A TGL was considered visualized
      on plain radiographs when an opacity of soft-tissue density was apparent in the
      posterior part of the Hoffa's fat pad. The TGL was identified in 29 of the 50
      (58%) sagittal MR images; a TGL was observed on the lateral plain radiographs of
      six patients (12%). Correlation with the MR images showed that, when visualized
      on plain radiographs, the ligament is at least 3 mm thick and completely
      surrounded by fat. Our study shows that the TGL is a normal variant that can be
      recognized frequently on lateral plain radiographs of the knee.

PMID- 1393412
TI  - Macrodystrophia lipomatosa: radiographic observations.
AB  - 23 cases of macrodystrophia lipomatosa (MDL) are reported showing a wide spectrum
      of radiographic findings. Typical findings were hypertrophy of all the mesodermal
      tissues of the affected digits with dramatic overgrowth of fat. Phalanges were
      enlarged both in length and transverse diameter, but the trabecular pattern was
      maintained. In one patient, the phalanges and metatarsals were elongated but
      thinned. In another case, all the phalanges and metatarsals of the great toe were
      small. The little toe was also involved in two cases. Articular surfaces were
      slanting. There was a high incidence of palmar and plantar involvement. In a few
      cases the forearm and leg were also involved. Other uncommon features observed
      were early maturation of epiphyseal centres of ossification of phalanges and
      metatarsals, syndactyly, polydactyly, brachydactyly and symphalangism.
      Angiography was uncharacteristic.

PMID- 1393413
TI  - Fatty infiltration of the liver: analysis of prevalence, radiological and
      clinical features and influence on patient management.
AB  - Over a 6-year period, in 1425 adult computed tomographic studies, radiological
      evidence of fatty infiltration of the liver (FIL) was found in 138 patients
      (9.7%). Patients with FIL had a mean age +/- SD of 45.9 +/- 15.7 years and 57%
      were males; the majority were Saudis (73%). Most patients (95%) had one or more
      underlying aetiological causes. Haematological and non-haematological
      malignancies with or without liver involvement were the most frequently
      encountered aetiological factors (66% of patients). FIL contributed to
      hepatomegaly or was associated with abnormality in one or more of the liver
      function tests in 30% and 39% of patients, respectively. Assessment of the
      various radiological patterns showed diffuse fatty changes in 68% of patients and
      solitary or multiple focal changes in 9% and 22%, respectively. 13 patients (9%)
      showed sparing of the caudate lobe within a diffuse fatty process. Patients with
      diffuse FIL had significantly higher values for alkaline phosphatase (p = 0.0016)
      and serum asparate aminotransferase (p = 0.0251) than those who had the focal
      pattern. FIL in 20 patients (14%) imposed a difficulty in making an appropriate
      diagnosis, led to inaccurate impressions, or forced unnecessary invasive or non
      invasive investigations. We conclude from our large series of patients that FIL
      is not uncommon in hospital practice and among those at risk should always be
      considered as an appropriate diagnosis.

PMID- 1393414
TI  - Accuracy of ultrasound and oral cholecystography in assessing the number and size
      of gallstones: implications for non-surgical therapy.
AB  - Prior to non-surgical therapy of gallstones it is important to assess their
      number and size. In order to evaluate the accuracy of ultrasound (US) and oral
      cholecystography (OCG) in counting and measuring gallstones, a prospective blind
      study was conducted to compare the results of US (n = 99) and OCG (n = 36),
      either alone or in combination (n = 34), with the number and size of gallstones
      retrieved after cholecystectomy. The number of gallstones was accurately
      estimated by US and OCG in 74% and 69% of the cases, respectively. In assessing
      the presence of up to three, five or 10 gallstones both US and OCG proved
      reliable. In measuring the size of gallstones, there was 19% accuracy with US
      compared with only 3% with OCG. With an accepted measurement error of 3 mm these
      values increased to 80% for US and 44% for OCG. US proved more reliable than OCG
      in discriminating gallstones smaller or larger than 10 mm and smaller or larger
      than 20 mm, but with US, detection of gallstones larger than 30 mm was
      problematic. Both US and OCG underestimated gallstone size. The combination of
      both techniques did not significantly improve the assessment of either number or
      size of gallstones compared with the results obtained with US or OCG alone. It is
      concluded that (1) both US and OCG have some limitations in assessing the number
      and size of gallstones, (2) the combination of both examinations does not improve
      accuracy, and (3) patient selection for non-surgical treatment of gallstones can
      be started by US alone.

PMID- 1393415
TI  - The optimum pressure of oxygen for radiotherapy of a mouse tumour.
AB  - Our previous studies have shown that there is more regrowth delay in mammary
      tumours irradiated in C3H mice after 25 Gy when breathing normobaric oxygen than
      in those breathing air, as might be expected. However, in both cases this
      radiation response was reduced in anaesthetized animals in comparison with
      unanaesthetized control mice, when a time interval of only 10 min was allowed
      after anaesthesia. After 25 min, however, the response in air returned to the
      control level and the oxygen group now showed significantly more
      radiosensitization. We have now found that when tumour-bearing mice were exposed
      to different pressures of oxygen for that 25-min period after the induction of
      anaesthesia, before the tumours were treated with 25 Gy, there was even more
      regrowth delay with 2 atm pressure than 1, but that there was no further
      advantage from using 3 atm pressure of oxygen. Our data suggest that 2 atm may be
      the optimal pressure to use in anaesthetized mice and there is even a small
      benefit from using this pressure in unanaesthetized animals for a transplanted
      C3H mammary tumour.

PMID- 1393417
TI  - A pilot study of accelerated fractionation in the radiotherapy of invasive
      carcinoma of the bladder.
AB  - 24 patients with muscle invasive carcinoma of the bladder were treated in a pilot
      study of twice daily fractionation at radiation doses of 1.8-2.0 Gy per fraction
      to total doses of 54-64 Gy to the bladder and 39.6-44 Gy to the whole pelvis. The
      treatment aim was to give 32 fractions in 22 days. The interfraction interval was
      a minimum of 6 h. The principle objective was to record acute and late tolerance,
      but local control and survival data is also presented. Acute radiation morbidity
      was scored according to the RTOG system. Grade 2 large bowel effects were seen in
      52% of patients, Grade 3 effects in 26% and there was one Grade 4 and one Grade 5
      effect. The mean duration of effect was 4.5 weeks although the more severe
      reactions were also more protracted. Grade 2 urinary effects occurred in 30% and
      Grade 3 in 17% of patients. The mean duration of effect was 7.2 weeks. There were
      no Grade 4 or 5 acute urinary effects. Late radiation morbidity was scored
      according to the EORTC/RTOG system and was assessable in 16 cases who survived
      more than 6 months. There were two cases (12%) of Grade 1 bowel toxicity, two
      cases of Grade 1 and three of Grade 2 urinary toxicity. There were no cases of
      late skin effects. Actuarial analysis at 2 years shows a local control
      probability of 56% and survival probability of 35%.

PMID- 1393416
TI  - Treatment planning for 131I-mIBG radiotherapy of neural crest tumours using 124I
      mIBG positron emission tomography.
AB  - Patients designated to receive 131I-meta-iodobenzylguanadine (mIBG) for the
      treatment of neural crest tumours have been scanned with 124I-mIBG using the MUP
      PET positron camera. Uptake was detected in tumour sites in lung, liver and
      abdomen. The tomographic images produced have allowed estimates to be made of the
      concentration of mIBG in both tumour and normal tissue. From these data it is
      possible to predict the radiation doses that would be achieved using therapy
      levels (up to 11 GBq) of 131I-mIBG. The levels of tumour uptake are between 0.5
      and 2.0 kBq/g indicating that the radiation doses to tumour would be in the range
      3 Gy to 7.5 Gy.

PMID- 1393418
TI  - An investigation into the effect of protective devices on the dose to
      radiosensitive organs in the head and neck.
AB  - A series of experiments were performed to determine the dose reduction afforded
      to radiosensitive organs in the head and neck by various protective devices.
      These included spectacles with plastic, standard glass, photochromic and lead
      glass lenses, a thyroid collar and a lead-acrylic face mask. The measurements
      were performed using an anthropomorphic phantom loaded with lithium fluoride
      thermoluminescent dosemeters, in conditions realistic of clinical practice.
      Irradiations were performed using scattered radiation produced by a pelvic
      phantom, for X-ray beams generated at 80 kVp and 110 KVp. It was found that the
      reduction in dose to the lens of the eye ranged between 0% and 97%, whilst the
      dose to the thyroid and oesophagus was reduced by between 76% and 97%, and was
      dependent on the protective device and tube potential employed. A reduction in
      brain dose of up to 81% was also measured, for the lead-acrylic face mask. Also
      presented is the ratio of organ dose to dose to the bridge of the nose for
      thyroid, oesophagus, brain and sinuses, as measured for the case of no head or
      neck protection.

PMID- 1393419
TI  - Evaluation and skeletal metastases.

PMID- 1393420
TI  - Errors due to non-uniform distribution of fat in dual X-ray absorptiometry of the
      lumbar spine.
AB  - Errors in spinal dual X-ray absorptiometry (DXA) were studied by analysing X-ray
      CT scans taken for diagnostic purposes on 20 patients representing a wide range
      of fat content. The mean difference between the fat thickness over the vertebral
      bodies and that over a background area in antero-posterior (AP) scanning was 6.7
      +/- 8.1 mm for men and 13.4 +/- 4.7 mm for women. For lateral scanning the mean
      fat thickness difference was only 4 mm for both sexes, but the dispersion was
      greater, with a standard deviation of 15 mm. To relate these differences to
      errors in bone mineral, measurements were made of the bone mineral equivalence of
      fat-equivalent materials on DXA machines from three manufacturers. 10 mm of
      adipose tissue was equivalent to -0.043 g/cm2 of hydroxyapatite. For AP scanning
      a non-uniform fat distribution leads to a mean overestimate of 0.029 g/cm2 for
      men and 0.057 g/cm2 for women. The error exceeded 0.1 g/cm2 in 10% of slices. For
      lateral scanning the error exceeded 0.1 g/cm2 (about 15% of normal) in a quarter
      of slices.

PMID- 1393422
TI  - A flexion and extension device for dynamic MR imaging of the neck.

PMID- 1393421
TI  - An afterloading technique utilizing The Royal London Hospital caesium-137 brain
      needle in an oral obturator.

PMID- 1393423
TI  - Digital cardiac imaging--the death knell of cineangiography?

PMID- 1393424
TI  - Tuberculosis of the ribs: computed tomographic findings.

PMID- 1393425
TI  - External carotid angioplasty in the treatment of developing stroke.

PMID- 1393426
TI  - Osteosarcoma metastatic to the kidney with invasion of the inferior vena cava.

PMID- 1393427
TI  - Case of the month. The third dimension.

PMID- 1393428
TI  - Radiation-induced hearing impairment--a pilot study in patients treated for
      malignant parotid tumours.

PMID- 1393429
TI  - Historical experiments predating commercially available computed tomography.
AB  - Computed tomography (CT) was a revolution in radiology. Commercially available CT
      scanners appeared in 1972, a joint effort between the EMI Company, Atkinson
      Morley's Hospital, London and the Department of Health and Social Security
      (DHSS). The name of Sir Godfrey Hounsfield will always be associated with these
      developments. Like most developments in science the breakthrough came by standing
      on the shoulders of giants and many experiments can, with the curious wisdom of
      hindsight, be considered precursors to CT. Gabriel Frank's patent in 1940 showed
      apparatus for back-projection CT and Takahashi developed equipment in the 1940s
      for reconstructing from a sinogram; in both cases using an optical "computer". A
      medical CT scanner was reportedly constructed in 1957 in Kiev. Transmission CT
      was performed by Kuhl in 1965. Cormack built an experimental scanner in 1963.
      Oldendorf identified what was needed for successful CT as early as 1960.
      Throughout the 1960s a host of independent workers were busy on the mathematical
      problems of reconstructing from projections with both medical scanning and non
      medical applications in mind. Experiments in early emission tomography influenced
      the development of CT. With imagination one can even see how close "classical"
      tomography, as started even before 1920, came to the realization of CT. The
      pioneering British radiographer Watson stands out from a galaxy of inventors. The
      lecture at Radiology and Oncology '91 in Brighton was a thumbnail sketch of the
      origins of radiological CT. A fuller story is told elsewhere (Webb, 1990).

PMID- 1393431
TI  - Lower urinary tract reconstruction in young patients.

PMID- 1393430
TI  - The use of theophylline, an adenosine antagonist in the prevention of contrast
      media induced nephrotoxicity.

PMID- 1393433
TI  - Renal carcinoma in patients undergoing nephrectomy: analysis of survival and
      prognostic factors.
AB  - A series of 155 patients who underwent nephrectomy for renal carcinoma between
      1965 and 1985 at Manchester Royal Infirmary were analysed for survival in
      relationship to presenting features, surgical staging and histopathology.
      Univariate and multivariate analyses were carried out. Five-year survival
      estimates for stage 1 disease were 81%, for stage 2 disease 65%, for stage 3
      disease 39% and for stage 4 disease 6%. An erythrocyte sedimentation rate (ESR)
      greater than 30 mm/h was associated with worse survival and a history of
      hypertension was associated with better survival. Renal vein invasion alone was
      related to worse survival. Perinephric fat invasion was also associated with
      worse survival and this association in the multivariate analysis was more
      significant than expected, suggesting that the principles of radical surgery
      should be observed. The presence of granular cells as opposed to clear cells
      worsened survival. Patients with papillary tumours had a better survival than
      those with solid tumours.

PMID- 1393432
TI  - Long-term follow-up of patients with hydronephrosis treated by Anderson-Hynes
      pyeloplasty.
AB  - A series of 21 patients with hydronephrosis (mean age 37 years) underwent an
      Anderson-Hynes pyeloplasty; a nephrostomy catheter was not used routinely. One
      patient developed urinary leakage post-operatively but this ceased following
      insertion of a ureteric catheter. Assessment was carried out after a mean
      observation time of 85 months. Clinical examination, laboratory investigations,
      urography and renography were performed pre-operatively and at follow-up. There
      was no evidence of stones or stenosis in the pelvis. Patients operated upon
      before the age of 30 years showed improved renal function. All patients had
      symptoms pre-operatively but only one had symptoms post-operatively. It was
      concluded that the results of surgical intervention in hydronephrosis are
      excellent, especially in patients aged less than 30 years.

PMID- 1393435
TI  - Ureteric complications of renal transplantation.
AB  - Of 507 consecutive recipients of renal allografts, 45 developed a urological
      complication. In 39 patients (7.7%) ureteric problems were implicated and these
      comprised 30 cases of obstruction and 9 cases of ureteric necrosis presenting as
      urinary leakage. In 7 patients ureteric obstruction resolved following a period
      of nephrostomy decompression; 10 patients were reconstructed surgically and this
      was successful in 8, with 2 patients requiring further surgical procedures. Ten
      patients were successfully treated by percutaneous stenting after dilatation of
      the stricture. Stenting failed in 4 patients and in 1 patient caused rupture of a
      calix. All 10 stents have now been removed and there is no recurrence of
      stricture (follow-up 32.0 +/- 8.6 months). Of the remaining 3 grafts, 2 were
      removed and the other graft had percutaneous removal of a ureteric calculus. The
      1-year survival rate of allografts in the ureteric complication group was 84.6%;
      in the recipients without a urological complication it was 81%. It was concluded
      that an active approach to ureteric problems following renal transplantation
      results in the rescue of the majority of allografts.

PMID- 1393434
TI  - Blood transfusion and survival following surgery for renal carcinoma.
AB  - The effect of peri-operative blood transfusion on survival after surgery for
      renal carcinoma was studied in 201 patients. In addition to blood transfusion,
      several other factors were included in a multivariate analysis. Using Cox's
      proportional hazards model, transfusion of more than 4 units of blood was found
      to be an independent prognostic factor in addition to tumour stage, erythrocyte
      sedimentation rate and macrohaematuria.

PMID- 1393436
TI  - Voiding dysfunction and urodynamic findings in patients with cervical spondylotic
      spinal stenosis compared with severity of the disease.
AB  - A group of 30 consecutive patients (26 men and 4 women, mean age 51 years), with
      clinically and radiologically verified cervical spondylosis causing radiculopathy
      and/or myelopathy, were questioned about voiding symptoms, examined
      urodynamically and subjected to tests of tibial somatosensory evoked potentials
      (SEP). Seventeen patients (61%) complained of irritative bladder symptoms and
      detrusor hyperactivity was demonstrated urodynamically in 13 (46%). Three (11%)
      experienced difficulty in emptying the bladder, and all of these had a hypotonic
      detrusor. The bladder was insensitive to cold in 36%, this and SEP abnormalities
      being more common in the patients with clinically severe myelopathy, whereas
      detrusor hyperactivity was found equally in all patients. Urodynamic
      investigation seems to provide additional information on the severity of the
      disease and is therefore recommended for wider use in these patients.

PMID- 1393437
TI  - Acute urinary retention. Comparison of suprapubic and urethral catheterisation.
AB  - A total of 86 consecutive patients who presented to the accident and emergency
      department with acute urinary retention due to prostatomegaly required
      catheterisation; 56 received suprapubic catheters and 30 were catheterised
      urethrally. Both groups were followed up for 3 years. Of the 30 patients
      catheterised urethrally, 12 (40%) developed urinary tract infections compared
      with 10 (18%) urinary tract infections in the 56 patients catheterised
      suprapubically. Five patients (17%) in the urethral group developed urethral
      strictures with no strictures in the suprapubic group. Two patients catheterised
      urethrally developed epididymo-orchitis and 1 developed septicaemia. None of the
      patients with suprapubic catheters developed these complications. Furthermore, 16
      patients catheterised suprapubically underwent successful trial clamping of their
      catheter, whereas 7 patients required recatheterisation following removal of
      their urethral catheters. We recommend that the use of suprapubic catheters
      should become the preferred initial treatment for acute urinary retention.

PMID- 1393438
TI  - In vivo detection by microscopic chromocystoscopy of concurrent urothelial atypia
      in superficial bladder cancer.
AB  - Microendoscopic observation of methylene blue-stained urothelial surfaces, so
      called microscopic chromocystoscopy (MCC), was undertaken in 65 patients with
      superficial bladder cancer (Ta and T1) and its effectiveness in detecting
      concurrent urothelial dysplasia or carcinoma in situ was studied. A total of 166
      biopsy samples were taken from 75 stained and 91 non-stained portions. Of 75
      methylene blue-stained areas, 21 were judged to be abnormal (MCC-positive) by
      microscopic observation. Fourteen of these 21 MCC-positive areas (67%) were
      proven to be abnormal histologically, while 7 of 54 MCC-negative portions (13%)
      were histologically abnormal. Only 4 of 91 biopsies (4%) from non-stained mucosa
      were proven to have urothelial atypia. In per patient figures, 1 or more
      concurrent field changes were detected in 15 of 65 cases (23%). MCC contributed
      to the diagnosis in 10 of these 15 patients.

PMID- 1393439
TI  - Initial combination chemotherapy with cisplatin, methotrexate and vinblastine in
      locally advanced transitional cell carcinoma--response rate and pitfalls. MRC
      Subgroup in Advanced Bladder Cancer (on behalf of the MRC Urological Working
      Party).
AB  - A total of 51 patients with locally advanced transitional cell carcinoma of the
      bladder were entered into a phase II study to evaluate the effect of initial
      cisplatin (100 mg/m2, Day 2) combined with methotrexate (30 mg/m2, Days 1 and 8)
      and vinblastine (4 mg/m2, Days 1 and 8). Of 44 evaluable patients, 25 (57%)
      achieved an objective response of their primary bladder tumour (complete response
      (CR): 4 patients; partial response (PR): 21 patients); 30 of the 36 patients with
      micturition disturbances obtained relief. Toxicity was acceptable, but dose
      modifications due to haematological or renal toxicity were required in 153 of the
      690 drug courses. Non-protocol dose modifications were performed 45 times. The
      experience gained in this trial emphasises the need for improved co-operation
      between urologists, radiologists and clinical oncologists in such multicentre
      phase II studies. Difficulties were observed in adhering to dose modification
      rules, assessing pre-treatment tumour size (due to variation in quality of
      measure and in timing relative to initial transurethral resection (TUR)) and
      defining response to chemotherapy (due to failure to perform mandatory
      investigations at the right time). This study also illustrates that the accepted
      criteria for assessing response in the primary bladder tumour are difficult to
      apply in practice and that the results of any study using this indicator lesion
      require caution in their interpretation.

PMID- 1393440
TI  - Intravesical instillation of beta-interferon in the treatment of bladder cancer.
AB  - A total of 36 patients with single superficial bladder cancer TNM stage Ta-T1/G2
      was studied over a 24-month period before entering the study to evaluate the
      efficacy and tolerance of high doses of beta-interferon (beta-INF); 24 patients
      had a primary tumour (group 1) and 12 had had more than 3 recurrences (group 2).
      They received 8 intravesical doses of beta-INF, 50,000,000 IU in 50 ml sterile
      water, at weekly intervals, 15 days after transurethral resection of the bladder
      (TURB). Efficacy was estimated by simple recurrence rate and by the person-years
      method. The recurrence rate was 25% in group 1 with a mean follow-up of 21.6
      months. Comparison with the recurrence rate of a historical control group treated
      only by TUR showed that there was a slight statistically significant difference.
      Group 2 had a recurrence rate of 100% in the period before beta-INF (follow-up 24
      months) and 91% after INF administration (mean follow-up 20.5 months). Patients
      were questioned about side effects before and after each treatment; tolerance of
      the drug was excellent. The results suggest that beta-interferon could be safely
      used as a prophylactic agent against the recurrence of primary superficial
      bladder cancer. Its efficacy seems comparable to that obtained with other current
      chemoprophylactic agents.

PMID- 1393441
TI  - Laparoscopic ligation of internal spermatic vein.
AB  - Laparoscopic procedures have long been a standard form of treatment for
      gynaecological disorders but have only recently shown promise in the evaluation
      and treatment of urogenital diseases, such as pelvic lymphadenectomy. We
      performed laparoscopic ligation of the bilateral internal spermatic veins in 15
      male pigs. The average operative time was 20 min and operative morbidity was
      minimal, comprising mild subcutaneous emphysema around the trocars. Engorgement
      of the spermatic vein proximal to the endoclip site was noted. There was no
      operative mortality. Laparoscopic ligation of the internal spermatic veins seems
      to be a feasible method for the treatment of varicoceles, especially bilateral
      lesions.

PMID- 1393442
TI  - Urine transparency as an index of absence of infection.
AB  - A visual assessment of the clarity of urine was used as an exclusion test to
      indicate the absence of infection; verified by dipslide culture, it was applied
      to 363 urine samples collected from patients attending 2 adult nephrology clinics
      over a period of 6 months. The crimped aluminium bowl used for collection of
      samples assisted the assessment of clarity. The sensitivity of the method
      compared with dipslide culture was 73%, with specificity and efficiecy both 58%.
      The predictive value of a negative test (clarity) was 97% with a false negative
      rate of 3%, enabling this simple examination to be used as an exclusion test for
      further testing. In simple terms, a clear urine is unlikely to be infected. It is
      also an advantage to have an immediate indicator of the absence of infection
      available at the clinic. Analysis of only those urines assessed as cloudy could
      result in financial savings and, from the clinics, a 56% reduction in workload.

PMID- 1393443
TI  - Current management of duplex-system ureteroceles: experience with 41 patients.
AB  - Experience is described of 41 infants and children with duplex-system
      ureteroceles, 25 presenting clinically and 16 by prenatal ultrasonography.
      Bladder outflow obstruction was rare but lower polar vesicoureteric reflux (VUR),
      usually of lesser grades, was common. Upper polar function, as assessed by 99mTc
      DMSA, was negligible in children with truly ectopic ureteroceles but well
      preserved in those where the lesion lay wholly intravesically. Lower polar
      function was good, even in the presence of secondary obstruction, except in 2
      infants with major VUR. Twenty-three patients were treated by upper polar
      nephrectomy plus aspiration of the ureterocele; 2 subsequently required
      ureterocele excision. Histology of excised specimens indicated that a more
      conservative approach would not have been rewarded. Where upper polar function
      was good, conservation was maintained in 3 cases by pyelopyelostomy and in 5 more
      by excision of the ureterocele plus bipolar ureteric reimplantation. Other
      operative strategies were employed in 2 cases. Finally, a defined group of 8
      children was managed expectantly without untoward results. It was concluded that
      the variable anatomy and function associated with duplex-system ureteroceles
      require a flexibile approach to treatment, including, possibly, no treatment at
      all.

PMID- 1393444
TI  - Posterior urethral valves in non-twin siblings.

PMID- 1393445
TI  - Two rare genital abnormalities: crossed testicular and scroto-testicular ectopia.

PMID- 1393446
TI  - Regression of lymphadenopathy in patient with prostatic carcinoma after hormonal
      manipulation.

PMID- 1393447
TI  - Right-sided varicocele caused by false aneurysm from aortic graft.

PMID- 1393449
TI  - Extraskeletal Ewing's sarcoma metastatic to penis.

PMID- 1393448
TI  - Primary actinomycosis of the urinary bladder.

PMID- 1393450
TI  - Haematuria after exercise following pelvic fracture.

PMID- 1393451
TI  - The rat-tail catheter in ureteroneocystostomy operations.

PMID- 1393452
TI  - The Autoinjector device: an aid to intracavernosal pharmacotherapy.

PMID- 1393453
TI  - Nephrostomy tubes resistant to removal.

PMID- 1393454
TI  - Re: Eosinophilic prostatitis and prostatic specific antigen. S. Liu et al. Br. J.
      Urol., 69, 61-63, 1992.

PMID- 1393455
TI  - Treatment of asymptomatic popliteal aneurysm: protection at a price.

PMID- 1393456
TI  - Anorectal reconstruction.

PMID- 1393457
TI  - Monitoring and cerebral protection during carotid endarterectomy.
AB  - Two recently published multicentre trials have confirmed the overall benefit of
      carotid endarterectomy in symptomatic patients with severe carotid artery
      disease. The key to improving further the long-term advantages of carotid
      endarterectomy, however, remains the continued reduction of the initial operative
      risk. While the principal responsibility for this continues to be borne by the
      surgeon, specifically in reducing technical error, the time is perhaps
      approaching when he or she might also be able to apply some of the recent
      advances in cerebrovascular research to reduce operative morbidity still further
      in the future. This article summarizes the aetiology and pathophysiology of
      operation-related neurological deficits and reviews current approaches towards
      intraoperative monitoring, cerebral protection and assessment of quality control.

PMID- 1393458
TI  - Chest physiotherapy for the surgical patient.
AB  - This article reviews the evidence that chest physiotherapy is effective in the
      prevention and treatment of pulmonary complications after major abdominal and
      thoracic surgery. There is some evidence that regular chest physiotherapy
      significantly decreases the incidence of pulmonary complications, although the
      mechanism of this effect is uncertain. It is not known whether chest
      physiotherapy is effective in the treatment of postoperative pulmonary
      complications after they have developed.

PMID- 1393459
TI  - In situ versus reversed femoropopliteal vein grafts: long-term follow-up of a
      prospective, randomized trial.
AB  - In a prospective, randomized trial, 226 patients undergoing femoropopliteal
      bypass for lower limb ischaemia were allocated to reversed (123 patients) or in
      situ (103) techniques. The groups were comparable for age, sex, incidence of
      diabetes, and indications for surgery. Eleven veins were rejected at operation,
      nine in the reversed group and two in the in situ group, leaving 114 reversed and
      101 in situ grafts for study. Cumulative patency rates were not significantly
      different between reversed and in situ grafts at any time up to 6 years after
      operation, with primary patency rates at 1, 3 and 5 years of 84.8, 69.5 and 62.4
      per cent for reversed grafts and 79.9, 71.2 and 63.5 per cent for in situ grafts.
      Small vein grafts (< 4 mm in diameter) were associated with patency rates at 1, 3
      and 5 years of 63.5, 46.7 and 36.0 per cent compared with 93.9, 82.5 and 75.9 per
      cent for vein grafts > or = 4 mm in diameter (P < 0.002, log rank test). The
      patency rates of small veins employed in situ and reversed were similar. The in
      situ technique confers neither short- nor long-term advantage over reversed vein
      grafting for femoropopliteal bypass.

PMID- 1393460
TI  - Efficacy of endoscopic transthoracic sympathectomy assessed by peroperative
      palmar temperature measurement.

PMID- 1393461
TI  - Success rates for rehabilitation of vascular amputees: implications for
      preoperative assessment and amputation level.
AB  - All lower limb amputations performed during 1986 and 1988 in eight hospitals in
      the south-east region were assessed. Of 440 amputations for vascular disease, 193
      were above-knee, 193 below-knee, 15 Gritti-Stokes, 15 through-knee and 24
      bilateral. Of the 440 patients, 75 died in hospital, 113 were considered
      unsuitable for a prosthesis and 252 (57 per cent) were referred for prostheses.
      Rehabilitation questionnaires were sent to 179 patients (41 per cent), as a
      further 54 had died and 19 had become known non-wearers before the study
      commenced. The response rate was 81 per cent; 102 patients completed the
      questionnaire, 21 were reported dead, and 22 were non-wearers. Of a maximum
      rehabilitation score of 12, 52 patients scored 6 or more (consistent with
      mobility on their artificial limb around the home), and 21 scored 9 or more (a
      standard accepted as successful rehabilitation). It is concluded that 10-15 per
      cent of amputees achieve mobility around the home on their prosthesis. Only 5 per
      cent, however, rehabilitate well and become independent of their wheelchair. When
      amputation is inevitable, more consideration should be given to surgery that
      optimizes wheelchair rehabilitation.

PMID- 1393462
TI  - Continuous ambulatory peritoneal dialysis in patients with aortic grafts.

PMID- 1393463
TI  - Systemic cytokine response after major surgery.
AB  - The systemic cytokine response to major surgical trauma was studied in 20
      patients undergoing elective aortic surgery and five patients after inguinal
      hernia repair. Tumour necrosis factor alpha and interferon gamma were not
      detected in these patients. An early and short-lived interleukin 1 beta (IL-1
      beta) response to major surgery was detected only by intensive sampling in the
      perioperative period. The IL-1 beta peak preceded a more marked interleukin 6 (IL
      6) response that peaked 4-48 h after surgery. IL-6 levels had fallen sharply by
      48-72 h in all patients who had an uneventful postoperative course. The IL-6
      peaks were significantly lower after hernia surgery than after major aortic
      operations (P < 0.001); IL-1 beta was not detected in any samples. Three patients
      undergoing aortic surgery developed unexpected major postoperative complications.
      IL-6 levels in this group were significantly higher than those of the other
      patients undergoing aortic surgery within 6-8 h of skin incision, and remained
      elevated for longer. These rises in plasma IL-6 levels preceded the clinical
      onset of major complications by 12-48 h. The systemic IL-1 beta and IL-6 response
      to surgical trauma increased with the severity of the surgical insult. An early,
      exaggerated IL-6 response was associated with the subsequent clinical development
      of major complications.

PMID- 1393464
TI  - Continuing experience with transaxillary excision of the first rib for thoracic
      outlet syndrome.
AB  - The results of transaxillary excision of the first rib for thoracic outlet
      syndrome are reported. During a 3-year period, 40 transaxillary rib resections
      were performed on 32 patients. The symptoms in 33 limbs were completely relieved
      and in a further four symptoms were improved. These results confirm that
      transaxillary excision of the first rib is the operation of choice in the
      management of thoracic outlet syndrome.

PMID- 1393465
TI  - Peripheral tuberculous lymphadenopathy: a review of 67 cases.
AB  - Peripheral tuberculous lymphadenopathy is the commonest form of extrapulmonary
      tuberculosis. Sixty-seven patients with peripheral tuberculous lymphadenopathy
      who presented to general surgeons and underwent lymph node biopsy between 1979
      and 1989 are reviewed. Fifty-four patients (81 per cent) were of Indian
      subcontinent ethnic origin and 13 (19 per cent) were of white ethnic origin. The
      sites most commonly affected were the cervical lymph nodes. Biopsy specimens
      obtained by open operation were sent for microbiological examination in all but
      13 cases, of whom seven were patients of white ethnic origin. Tuberculous
      lymphadenopathy remains an important differential diagnosis of cervical
      lymphadenopathy and it is essential that peripheral lymph node biopsies are
      examined both histologically and microbiologically.

PMID- 1393466
TI  - Subclinical injuries in lacerations to the forearm and hand.
AB  - This report describes the incidence and severity of subclinical injuries to
      underlying structures in lacerations to the hand and forearm. One hundred
      consecutive hand and forearm lacerations that penetrated the full thickness of
      subcutaneous tissue were studied prospectively. Lacerations were explored under
      either biceps or forearm tourniquets. Injuries, treatment, tourniquet time,
      causative agent and complications were recorded. In all, 97 patients sustained
      100 lacerations. A total of 49 deep injuries were discovered, none of which was
      detected clinically before exploration. Of these, 33 were tendon lacerations; 21
      tendons, including three flexor tendons, were repaired. Nineteen patients
      required treatment in a volar slab for at least 3 weeks. Five patients of 49
      returning for review developed wound infection. No patient developed significant
      problems related to the tourniquet, which was inflated for a mean time of 4.9
      min. There is a high incidence of subclinical injury in full-thickness
      lacerations of the forearm and hand. These should be explored under tourniquet,
      which should minimize complications such as wound infection and delayed tendon
      rupture.

PMID- 1393467
TI  - Parotid disease and human immunodeficiency virus infection in Zambia.
AB  - Among the salivary glands the parotid is unusual in that it contains lymphoid
      tissue within its capsule. The focus of infection with human immunodeficiency
      virus (HIV) is the lymphatic system and this results in a specific HIV-related
      pathology in the parotid. This 2-year surgical audit of parotid disease in HIV
      infected patients in Lusaka shows patients presenting with parotid
      lymphadenopathy, bilateral diffuse parotid enlargement and parotid
      lymphoepithelial cysts. Clinical presentation and management are discussed.

PMID- 1393469
TI  - Successful splenectomy for lymphoproliferative disease in octogenarians.

PMID- 1393468
TI  - Breast cancer in Nigerian women.
AB  - A combined retrospective (1971-1980) and prospective (1981-1990) study of the
      epidemiology, clinical characteristics and pathology of breast cancer in a black
      African population was carried out. There were 1946 biopsy-proven cases, with a
      rate frequency of 33.6 per 100,000 patients per year. The age range was 14-96
      years but 70 per cent of patients were between 26 and 50 years old. The
      cumulative frequency of cancer was 0.8 per cent at age < 20 years and 3.3 per
      cent at age < 25 years; the peak age range for disease was 36-45 years. Of 1842
      evaluable patients, 17.2 per cent presented with stages I or II cancer and 73.8
      per cent with stage III disease. The dominant histopathological type was
      infiltrating ductal cancer (49.2 per cent), followed by undifferentiated
      anaplastic carcinoma (33.3 per cent). Burkitt's lymphoma occurred in five
      patients and developed concurrently and rapidly during lactation in four. The
      prospective study did not demonstrate that age at menarche or first full-term
      pregnancy, duration of breast feeding or parity were risk factors in black women.

PMID- 1393470
TI  - Managing swabs in the operating theatre: a new method.
AB  - The swab count has traditionally used a swab rack. A new alternative 'bag' method
      involves placing used swabs in batches of five into plastic bags which are sealed
      and stored in a bin. A randomized prospective study was carried out to compare
      these two methods. Twenty consecutive ear, nose and throat cases were randomized
      to rack or bag collection. Swab-related activities were divided into three
      categories and analysed by formal time-and-motion criteria. Blood contamination
      of operating theatre and circulating personnel was recorded. The time involved in
      all three swab-related activities was significantly less using the bag technique.
      There was no theatre blood contamination using this method, but significant
      contamination occurred using the rack. Circulating theatre personnel were
      minimally contaminated in two cases using the bag method but were grossly
      contaminated in all ten cases using the rack method. The bag technique is
      therefore safe and time efficient.

PMID- 1393471
TI  - Total dysphagia from intramural haematoma following sclerotherapy for oesophageal
      varices.

PMID- 1393472
TI  - Mechanism of action of injection therapy for bleeding peptic ulcer.
AB  - The effects of intramucosal injection of 1:100,000 adrenaline, 5 per cent
      ethanolamine and normal saline were determined in experimentally created, acutely
      bleeding gastric mucosal wounds in rabbits. The mean(s.d.) bleeding rate was
      decreased from 2.3(0.4) to 0.2(0.02) ml/min by adrenaline (P < 0.01), but
      increased by 1 ml 5 per cent ethanolamine to 4.0(0.6) ml/min (P < 0.05). Normal
      saline had no haemostatic effect, suggesting that local tamponade is not
      important. In separate experiments endoscopic injections of 5 per cent
      ethanolamine, 1:100,000 adrenaline and normal saline were made in the gastric
      antrum of rabbits. After 48 h the degree of inflammation was greatest with
      ethanolamine but, despite tissue necrosis and venous thrombosis, neither
      endarteritis nor arterial thrombosis occurred. Injections of 5 per cent
      ethanolamine and 80 per cent ethanol placed next to the ear arteries of rabbits
      caused local ulceration and necrosis, but endarteritis and arterial thrombosis
      were again absent.

PMID- 1393473
TI  - Laparoscopic repair of perforated peptic ulcer.

PMID- 1393475
TI  - Duodenogastric reflux enhances growth and carcinogenesis in the rat pancreas.
AB  - Surgery for peptic ulcer disease may increase the risk of pancreatic cancer. The
      effect of duodenogastric reflux on pancreatic carcinogenesis was tested, and
      changes in the circulating levels of cholecystokinin (CCK) and gastrin were
      measured. Male Wistar rats (n = 40) weighing 250-300 g were randomized to undergo
      gastrotomy (control) or split gastrojejunostomy (to produce complete
      duodenogastric reflux) and then to receive azaserine (30 mg/kg/week
      intraperitoneally) or saline injections for 3 weeks. At 6 months, blood CCK was
      assayed and the pancreas was excised for quantitative estimation of atypical
      acinar cell foci (AACF), the precursor lesions of carcinoma. Rats that had
      undergone split gastrojejunostomy weighed 15-19 per cent less than controls (P <
      0.05), but their relative pancreatic weight (mg pancreas per 100 g body-weight)
      was 52-60 per cent greater (P < 0.001). Acidophilic AACF occurred only in
      azaserine-treated rats with duodenogastric reflux. Although plasma CCK
      concentrations were unchanged, split gastrojejunostomy increased basal and
      postprandial gastrin levels by 98-175 per cent (P < 0.05). Duodenogastric reflux
      produces sustained hypergastrinaemia and promotes experimental pancreatic
      carcinogenesis.

PMID- 1393474
TI  - Selective necrosis in hamster pancreatic tumours using photodynamic therapy with
      phthalocyanine photosensitization.
AB  - Photodynamic therapy (PDT) is often thought to be able to effect selective tumour
      necrosis. This therapeutic selectivity, based on transient differences in tumour:
      normal tissue photosensitizer concentration ratios, is rarely useful clinically
      in extracranial tumours, although PDT itself may be of value by virtue of the
      nature of the damage produced and healing of normal tissue by regeneration. This
      report describes the effects of PDT on normal pancreas and chemically induced
      pancreatic cancers in the hamster, where a different mechanism of selective
      necrosis may be seen. Photosensitizer distribution in normal and neoplastic
      pancreas was studied by chemical extraction and fluorescence microscopy.
      Correlation of distribution studies with necrosis produced by PDT shows that the
      photodynamic dose (product of tissue concentration of sensitizer and light dose)
      threshold for damage is seven times as high for normal pancreas as for pancreatic
      cancer. Tumour necrosis extended to the point where tumour was invading normal
      areas without damaging the normal tissue. In rat colonic cancer, photodynamic
      dose thresholds in tumour and normal tissue are similar and so such marked
      selectivity of necrosis is not possible. The reason for this selectivity in the
      pancreas is not clear, but recent evidence has suggested a difference in response
      to PDT between normal and neoplastic pancreatic cell lines and the presence of a
      singlet oxygen scavenger in normal pancreas is postulated. Furthermore, the
      present fluorescence microscopy studies suggest that tumour stroma contains the
      highest level of photosensitizer and thus receives the highest photodynamic dose
      during PDT. These results suggest a possible role for PDT in treating small
      pancreatic tumours or as an adjuvant to other techniques, such as surgery, that
      reduce the main bulk of tumours localized to the pancreas.

PMID- 1393476
TI  - Left hepatic vein kinking after right hepatectomy: a rare cause of acute Budd
      Chiari syndrome.

PMID- 1393477
TI  - Renal tubular cell injury and serum phospholipase A2 activity in acute
      pancreatitis.
AB  - Early diagnosis of threatening renal complication is essential for the adequate
      treatment of acute pancreatitis. Deposition of phospholipase A2 (PLA2) in rat
      renal proximal tubular cells has been observed in experimentally induced acute
      pancreatitis. The value of measuring the catalytic activity of PLA2 in serum as
      an early warning of developing renal tubular cell injury was therefore
      investigated in a prospective study of 31 consecutive patients suffering from
      acute pancreatitis. A positive correlation was found (r = 0.66, P < 0.001)
      between the highest serum PLA2 activity, as measured early in the course of acute
      pancreatitis, and the highest N-acetyl-beta-glucosaminidase (NAG):creatinine
      ratio in the urine. The correlation between the highest serum concentration of
      immunoreactive pancreatic PLA2 and the highest urinary NAG:creatinine ratio was
      weaker (r = 0.36, P < 0.05). These results indicate that the measurement of the
      catalytic activity of PLA2 in serum early in acute pancreatitis may provide a
      simple test for the detection of threatening renal complication.

PMID- 1393478
TI  - Tuberculosis of the pancreas.

PMID- 1393479
TI  - Laparoscopic cholecystectomy as a routine procedure for gallstones: results of an
      'all-comers' policy.
AB  - A total of 165 consecutive patients with gallstones were considered for
      laparoscopic cholecystectomy. Three were excluded. The median age was 52 years
      and 76 per cent were women. Eighteen patients underwent urgent operation.
      Laparoscopic cholecystectomy was successful in 160 of the 162 patients (99 per
      cent). The two failures were the result of dense adhesions and stones in the bile
      duct. There were no deaths but major complications occurred in three patients:
      fenestration of the colon sutured laparoscopically; bleeding from a cannulation
      site and subsequent laparotomy for a strangulated hernia; and subphrenic abscess.
      There were 13 minor complications, but no bile duct injuries or peritonitis. The
      median postoperative hospital stay was 1 day. Bile duct stones were present in 14
      patients (9 per cent) and were removed by endoscopic sphincterotomy (11
      patients), by laparoscopic exploration of the common duct (two) and by conversion
      to laparotomy (one). These results suggest that laparoscopic cholecystectomy is
      applicable to the large majority of patients who require elective or urgent
      cholecystectomy, if appropriate radiological and endoscopic support is available.

PMID- 1393480
TI  - Hemihepatic vascular occlusion using intraoperative ultrasonography: a simple
      technique.

PMID- 1393481
TI  - Management of common bile duct stones using a second-generation extracorporeal
      shockwave lithotriptor.
AB  - Fifty-four patients with common bile duct stones (8-36 mm in diameter) that could
      not be removed after endoscopic sphincterotomy, even with the use of mechanical
      lithotripsy, underwent extracorporeal shockwave lithotripsy (ESWL) using a
      Siemens Lithostar. Their median age was 75.5 (range 34-89) years. Patients
      received 4000-6000 shocks per session over approximately 60 min. Seventeen
      underwent two sessions and two patients three or more. Thirty-seven patients had
      one stone, ten had two, and seven had three or more. Spontaneous clearance of
      fragments occurred in only three patients before further endoscopic retrograde
      cholangiopancreatography was performed to remove fragments. Stones were removed
      and ducts cleared endoscopically in 35 patients, giving a total of 38 of 54
      patients (70 per cent) with complete duct clearance. Fragmentation in response to
      lithotripsy was dependent on stone size; the number of stones had little effect.
      ESWL was well tolerated without any haematological or biochemical abnormality.
      Computed tomography in the first 20 patients showed no hepatic or pancreatic
      change after treatment. ESWL combined with endoscopic extraction of fragments is
      an alternative to surgery when preliminary endoscopic extraction and mechanical
      lithotripsy have failed.

PMID- 1393482
TI  - Operative common bile duct imaging by operative cholangiography and flexible
      choledochoscopy.
AB  - A consecutive series of 108 common bile duct (CBD) explorations was studied to
      examine the efficacy of routine operative cholangiography and flexible
      choledochoscopy in the identification of choledocholithiasis. CBD exploration was
      performed according to the findings of routine operative cholangiography. Nine
      negative explorations were performed, only one of which would have been avoided
      had selective cholangiography been employed. Eight patients had unsuspected
      choledocholithiasis that would have been missed if selective operative
      cholangiography had been used. Flexible choledochoscopy identified CBD stones on
      97 occasions; no additional retained stones were found on subsequent T tube
      cholangiography. In two cases stones were seen but could not be removed;
      immediate identification allowed planning for early removal. Flexible
      choledochoscopy is the most effective method of CBD exploration and should be
      used in all patients with suspected choledocholithiasis.

PMID- 1393483
TI  - Laparoscopic versus open appendicectomy: a prospective evaluation.
AB  - A prospective evaluation of laparoscopic surgery for acute appendicitis over a 6
      month period is reported. Sixty-five patients with signs and symptoms of
      appendicitis necessitating surgery were assigned to open (n = 36) or laparoscopic
      (n = 29) appendicectomy. Thirty-seven patients were female (22 open) and 28 were
      male (14 open). The median age was 24 (range 14-64) years for open appendicectomy
      and 18 (range 14-60) years for the laparoscopic procedure. The mean postoperative
      stay for open operation was 4.8 (range 1-21) days and for the laparoscopic route
      2.2 (range 1-11) days (P < 0.05). Inflammation was confirmed histologically in 72
      per cent of the open cases and in 74 per cent of the laparoscopic cases (P not
      significant). The wound infection rate was 11 per cent (n = 4) for open and 4 per
      cent (n = 1) for laparoscopic appendicectomy (P < 0.05). The median anaesthesia
      time was 52 (range 15-90) min for open appendicectomy and 48 (range 20-120) min
      for laparoscopic surgery (P not significant). After open appendicectomy patients
      had a median of 5 (range 2-12) intramuscular injections of analgesia compared
      with a median of 1 (range 0-5) in the laparoscopic group (P < 0.05). Two
      laparoscopic operations were converted to an open procedure. The results suggest
      that emergency laparoscopic appendicectomy should be explored further as an
      alternative to open surgery for acute appendicitis.

PMID- 1393484
TI  - Temporary abdominal closure: a new product.

PMID- 1393485
TI  - Role of sequential leucocyte counts and C-reactive protein measurements in acute
      appendicitis.
AB  - The accurate clinical diagnosis of acute appendicitis is difficult, and many
      techniques have been suggested to improve diagnostic accuracy such as
      laparoscopy, ultrasonography and barium enema examination. In this study serial
      total leucocyte counts and serial C-reactive protein (CRP) concentrations in
      acute appendicitis were measured. The sensitivity and specificity of serial
      leucocyte counts in acute appendicitis were 92 and 100 per cent, and for CRP
      concentrations 69 and 75 per cent, respectively. The sensitivity and specificity
      of serial total leucocyte counts fulfilled the criteria for a diagnostic test. It
      is suggested that in patients with equivocal clinical findings, clinical
      observation combined with serial leucocyte counts may improve decision making.

PMID- 1393486
TI  - Decreased sensitivity of muscarinic but not 5-hydroxytryptamine receptors of the
      internal anal sphincter in neurogenic faecal incontinence.
AB  - Previous studies of the internal anal sphincter in patients with neurogenic
      faecal incontinence have indicated an abnormality of the adrenergic innervation,
      but little is known about the responsiveness of other receptors in the internal
      and sphincter in this condition. In this study the in vitro sensitivity to
      carbachol and 5-hydroxytryptamine (5-HT) of muscle strips from patients with
      neurogenic incontinence (n = 6 and n = 7) and from control patients (n = 9 and n
      = 10) was examined. Preparations of internal and sphincter from patients with
      incontinence were less sensitive to the relaxant actions of carbachol than
      preparations from the control group. The pD2 value for carbachol (i.e. the
      negative logarithm of the concentration for half-maximal response) was
      significantly greater in the controls than in the incontinent group (mean(s.e.m.)
      6.03(0.15) versus 5.43(0.24), P < 0.05). There was no significant difference in
      the contractile responses to 5-HT, which had pD2 values of 6.93(0.13) and
      6.63(0.27) for the control and incontinent groups respectively. The unaffected
      state of the 5-HT receptor and the subsensitivity of the muscarinic receptor are
      discussed in relation to intrinsic neural control of the internal and sphincter
      in neurogenic faecal incontinence.

PMID- 1393487
TI  - Screening for colorectal carcinoma: an analysis of the sensitivity of haemoccult.
AB  - The sensitivity of Haemoccult for asymptomatic colorectal carcinoma has been
      estimated in a large randomized controlled trial of mass population screening,
      with a minimum follow-up of 2 years. A total of 111 cancers were diagnosed in
      those who completed the screening tests; of these, 36 appear to have been missed
      by Haemoccult and 75 were detected by the test, giving an overall sensitivity of
      67.6 per cent. Haemoccult was shown to be significantly more sensitive for
      carcinoma of the sigmoid and descending colon than for rectal or right-sided
      cancers (81 versus 45 and 47 per cent, respectively). The sensitivity was higher
      when tests were completed over 6 rather than 3 days (74 versus 65 per cent), but
      this difference was not statistically significant. There was no evidence for a
      detrimental effect on tumour stage of a false-negative Haemoccult test; indeed, a
      higher proportion of the interval cancers were Dukes' A tumours than cancers in
      the control group.

PMID- 1393488
TI  - Local recurrence after anterior resection for rectal cancer using a double
      stapling technique.
AB  - Fifty-five patients of mean age 69 (range 41-96) years with rectal cancer (Dukes'
      A:B:C, 11:24:20) underwent anterior resection using a double stapling technique
      under the care of one consultant surgeon between 1983 and 1988. The mean distance
      of the anastomosis from the anal margin was 7.2 (range 4-13) cm. The clinical
      leak rate was 9 per cent (five patients). There were three postoperative deaths
      from pulmonary embolism, lower limb ischaemia and renal failure. On prospective
      follow-up, 35 patients had no evidence of local or systemic cancer a median of 32
      (range 24-84) months after operation; seven have died from unrelated diseases and
      ten from metastatic cancer. Pelvic recurrence, in four patients at 9, 11, 12 and
      50 months, has occurred only in association with widespread metastasis. These
      results suggest that the theoretical risks of an increase in the local recurrence
      rate of rectal cancer after resection using a double stapling technique are not
      substantiated.

PMID- 1393490
TI  - Comparison of minimal and conventional surgery in patients with bleeding peptic
      ulcer: a multicentre trial.

PMID- 1393489
TI  - Timing and method of reversal of Hartmann's procedure.
AB  - The outcome of 145 patients undergoing Hartmann's resection between 1973 and 1989
      has been reviewed. The mortality rate of the primary procedure was 8 per cent.
      Eighty patients proceeded to reanastomosis. Multifactorial analysis of these
      patients was undertaken to determine the risk involved. The interval between the
      primary and secondary procedures was found to be the most important factor. Six
      of 12 patients had clinical evidence of a leak when this interval was < 3 months,
      compared with seven of 28 for 3-6 months, and none of 40 when the second
      operation was delayed for > 6 months. All deaths (three patients) and clinical
      septicaemia (four) occurred in the two 'early' groups. All colovaginal fistulae
      (three patients) and strictures (three) were associated with stapled anastomoses.
      No association was found between the complication rate following reanastomosis
      and the initial pathology or grade of surgeon undertaking the secondary
      operation.

PMID- 1393491
TI  - Preoperative chemotherapy for cancer of the oesophagus.

PMID- 1393492
TI  - Management of the perineal wound following abdominoperineal resection:
      prospective study of three methods.

PMID- 1393493
TI  - Management of the perineal wound following abdominoperineal resection:
      prospective study of three methods.

PMID- 1393494
TI  - Adjuvant herbal treatment for gallstones.

PMID- 1393495
TI  - Parietal seeding of carcinoma of the gallbladder after laparoscopic
      cholecystectomy.

PMID- 1393496
TI  - Bile duct injury following laparoscopic cholecystectomy.

PMID- 1393497
TI  - Bile duct injury following laparoscopic cholecystectomy.

PMID- 1393498
TI  - Parietal seeding of carcinoma of the gallbladder after laparoscopic
      cholecystectomy.

PMID- 1393499
TI  - Hippocampal volumetric and morphometric studies in frontal and temporal lobe
      epilepsy.
AB  - The most common temporal lobe pathology is Ammons Horn sclerosis (AHS), and
      several different imaging techniques have been utilized to detect this with
      varying success. We describe the clinical application of magnetic resonance
      imaging (MRI) using a three-dimensional volume technique which allows total
      hippocampal volume to be measured and symmetry evaluated. Hippocampal surface
      area was calculated in sequential 1.5 mm thick contiguous images, using a GE IC
      workstation. Total volumes and surface areas were calculated. The cross-sectional
      surface area at 1.5 mm intervals was displayed graphically, permitting
      morphometric analysis of the hippocampus throughout its length. Focal atrophy
      within any part of the hippocampal formation (HF) and its extent could thus be
      assessed. Patients with well-lateralized temporal lobe epilepsy (TLE) (n = 20)
      and well-defined frontal lobe epilepsy (FLE) (n = 20) were studied, and volumes
      compared with normal values derived from 10 neurologically normal controls.
      Asymmetric hippocampal volume loss was demonstrated in all 20 patients with
      clinically typed TLE, but not in normal controls or patients with FLE. Volume
      loss distribution was anterior in 12 patients, posterior in one patient and
      widespread in seven patients. Secondarily generalized seizures were strongly
      associated with widespread loss. This method of surface area and volumetric
      analysis of the hippocampus in TLE can demonstrate asymmetry and focal
      involvement, and help distinguish between hippocampal and frontal pathologies.

PMID- 1393500
TI  - Movement-related potentials recorded from supplementary motor area and primary
      motor area. Role of supplementary motor area in voluntary movements.
AB  - Movement-related potentials (MRPs) were recorded from subdural electrodes
      chronically implanted in the interhemispheric fissure in two patients being
      evaluated for epilepsy surgery. Different types of movements (finger, foot,
      tongue and vocalization) were executed. Foot movements elicited a clearly
      defined, well-localized slow negativity or positivity (Bereitschaftspotential,
      BP) preceding electromyogram (EMG) onset. These BPs were seen from the
      contralateral primary motor foot area and also from bilateral supplementary motor
      areas (SMAs) with equivalent amplitudes and temporal evolutions. A steeper
      potential [negative slope (NS')] occurred about 300 ms before EMG onset and the
      motor potential (MP) started 100 ms before EMG onset. Negative slopes and MPs
      also arose from the contralateral primary motor area as well as from the
      bilateral SMAs. Finger movements elicited well-localized BPs and NS' which were
      generated from the bilateral SMAs, but were of higher amplitude on the
      contralateral SMA. Motor potentials started 50 ms prior to EMG onset and arose
      exclusively from the contralateral SMA. Tongue protrusions and vocalizations also
      elicited BP, NS' and MP which were seen in the bilateral SMAs. Movement-related
      potentials for different types of movements had a somatotopic distribution in the
      SMA, which was consistent with the SMA somatotopic organization defined by
      electrical simulation. Movement-related potentials for tongue movements and
      vocalization had a similar distribution and waveform. It was concluded that
      bilateral SMAs generate well-defined MRPs consistent with the assumption that the
      SMA plays a significant role in the organization of voluntary movements. However,
      the MRPs from the bilateral SMAs do not have characteristics which are different
      from those of the primary motor area. This suggests the hypothesis of
      'supplementary' function for SMA, and does not support the hypothesis of
      'supramotor' function.

PMID- 1393501
TI  - Effects of focal transcranial magnetic stimulation on simple reaction time to
      acoustic, visual and somatosensory stimuli.
AB  - In a simple reaction time (RT) paradigm, magnetic stimulation of different
      intensities was delivered over different scalp positions and at variable delays
      before (negative) or after (positive) the go-signal. Magnetic stimulation
      shortened RT to different go-signals (auditory, visual and somatosensory stimuli)
      by approximately 30 ms when delivered over the motor cortex contralateral to the
      responding arm at intensities below motor threshold. This effect was maximal at a
      delay of approximately +10 ms. A similar effect was found with suprathreshold
      stimulation to the ipsilateral motor cortex. Magnetic stimulation over other
      scalp areas did not affect RT regardless of the delay. No differences were found
      between the effects on elbow flexion and thumb abduction. The shortening of RT
      was not associated with changes in the timing development of premovement
      excitability increase in the motor cortex. We conclude that magnetic stimulation
      shortens RT by inducing an earlier initiation of this excitability increase.

PMID- 1393502
TI  - Conceptual apraxia in Alzheimer's disease.
AB  - Theoretical models of praxis have two major components, a praxis conceptual
      system that includes knowledge of tool use and mechanical knowledge and a praxis
      production system that includes the information needed to program skilled motor
      acts. Because patients with Alzheimer's disease may have an impairment of the
      central conceptual system, we wanted to learn if they had a conceptual apraxia by
      testing their knowledge of the type of actions associated with tool use, their
      ability to associate tools with objects that receive their action, their ability
      to understand the mechanical nature of problems and the mechanical advantages
      tools may afford. We studied 32 subjects with probable Alzheimer's disease and 32
      controls by examining tool-action relationships and tool-object associations. We
      tested mechanical knowledge by having subjects select alternative tools and solve
      mechanical puzzles by developing new tools. The Alzheimer's group was subdivided
      into four groups based on the presence or absence of ideomotor apraxia and a
      lexical-semantic deficit. Results indicated that each of the four Alzheimer's
      groups differed from normal controls on at least some measures of conceptual
      apraxia, suggesting that Alzheimer's patients do have a disturbance of the praxis
      conceptual system and that impairment of this system is not directly related to
      language impairment or ideomotor apraxia.

PMID- 1393503
TI  - Identifying the afferents involved in movement-induced pain alleviation in man.
AB  - It has been clearly established that the perception of nociceptive stimulus
      decreases in intensity when movement is initiated in the part of the body to
      which the stimulus is applied. The pain alleviation is probably at least partly
      due to the activation of afferents which occurs during the movement. The present
      experiments were carried out with a view to investigating which groups of
      afferent fibres is mainly responsible for the gating of the nociceptive messages
      which occurs during movements. In eight volunteers we investigated the changes in
      the amplitude of the nociceptive leg flexion reflex (RIII) when the subjects were
      at rest, when they were performing active or passive ankle movements and when the
      spindle proprioceptive pathway was mobilized by applying vibratory stimulation to
      the Achilles tendon. Similar experiments were also carried out with eight other
      volunteers after anaesthetizing the ankle skin mechanoreceptors. This method was
      chosen because a clear-cut correlation is known to exist between the amplitude of
      the nociceptive motor reflex and the intensity of the pain perceived by the
      subject. The data obtained clearly show that anaesthesia of cutaneous
      mechanoreceptors connected to the large diameter afferent fibres prevented the
      decrease in the motor response which otherwise accompanied both active and
      passive movements. Activation of the Ia fibre group by tendon vibration resulted
      on the contrary in an increase in the amplitude of the motor response. Movement
      induced pain alleviation therefore does not mainly involve the activation of the
      Ia group of fibres.

PMID- 1393504
TI  - Texture discrimination in carpal tunnel syndrome.
AB  - The ability to discriminate textured surfaces was measured in patients with
      carpal tunnel syndrome (CTS). Patients were initially diagnosed using clinical
      and electrophysiological criteria. The textured surfaces were gratings of
      alternating ridges and grooves. The gratings differed in their spatial period
      only, with the ratio of the ridge width to the groove width remaining constant
      (1:5). A two-alternative forced-choice paradigm was employed in which subjects,
      both patients and age-matched controls, rubbed their index finger (D2) or little
      finger (D5) back and forth across the surfaces. The grating spatial period at
      which subjects could discriminate a difference between the standard grating
      (spatial period = 2000 microns) and the comparison grating (spatial period in the
      range 2000-2900 microns) with a probability of 0.75 was taken as the measure of
      discriminative ability. Statistical comparison of the mean 75% values showed
      that: (i) when patients used D2 their discriminative ability was significantly
      impaired in comparison with the discriminative ability of controls using either
      D2 or D5; (ii) there was no significant difference in discriminative ability
      between patients and controls when patients used D5 to discriminate the textures;
      (iii) the 75% values for patients using D2 or D5 did not differ significantly.
      The degree of abnormality of each patient's sensory evoked potential did not
      allow us to predict their subsequent performance on the discrimination task.

PMID- 1393505
TI  - Recurrent Guillain-Barre syndrome. Clinical and laboratory features.
AB  - The clinical and laboratory features of recurrent Guillain-Barre syndrome (RGBS)
      were reviewed in 12 patients in whom a total of 32 episodes fulfilled accepted
      criteria for Guillain-Barre syndrome (GBS). All patients were asymptomatic or
      only mildly symptomatic between attacks. In a given patient, the time to reach
      peak deficit from the onset of symptoms, the functional grade at peak deficit and
      the duration of the intervals between episodes varied considerably and
      unpredictably from one episode to the next. Analysis of these parameters across
      the entire group revealed no significant change as the number of attacks
      increased. The distribution of weakness varied between episodes with the possible
      exception of features of the Miller Fisher variant which were more constant.
      Tremor was noted in two patients and enlarged nerves in one patient. There was no
      evident response to immunosuppressive therapy. Results of cerebrospinal fluid
      (CSF) analysis and nerve conduction studies during recurrences were those
      expected in typical monophasic GBS. On nerve biopsy, onion bulb formations were
      sometimes observed after several recurrences. The following characteristics of
      RGBS may be sufficiently distinctive from those of chronic relapsing
      polyneuropathy to justify their nosological separation: rapid onset of symptoms
      with subsequent complete or near complete recovery, high incidence of an
      antecedent illness, lack of an apparent response to immunosuppressive therapy and
      normal CSF protein levels at the onset of a recurrence.

PMID- 1393506
TI  - Torsional nystagmus. A neuro-otological and MRI study of thirty-five cases.
AB  - Thirty-five patients with torsional nystagmus (TN) underwent vestibular and
      ocular motor assessment and magnetic resonance image (MRI) scanning of the head.
      Patients were divided into two groups according to whether TN was predominant and
      present in primary gaze (Group I, 23 patients) or elicited by head positioning or
      gaze deviation and less prominent than other concurrent nystagmus (Group II, 12
      patients). The main aetiologies in both groups were demyelination, vascular
      disease and posterior fossa tumours. In Group I, a frequent pattern of findings,
      occurring in 30-50% of cases, was a caloric canal paresis contralateral to the
      direction of the fast phases ('beat') of the TN, whereas the duration of
      horizontal caloric/rotational nystagmus and the slow-phase eye velocity of
      pursuit and of optokinetic nystagmus were all reduced in the direction of
      beating. The TN was more frequently and consistently modulated by vertical canal
      stimuli (head oscillation in roll) than by otolith stimuli (static tilt).
      Statistical analysis of the MRI showed significant overlap of abnormal MRI
      signals in the area of the vestibular nuclei, on the side opposite to the beat
      direction of TN. These results suggest that TN originates in a central imbalance
      of vertical semicircular canal function, resulting from lesions involving the
      vestibular nuclei on the opposite side of the TN. Group II was heterogeneous with
      no consistent pattern of neuro-otological findings, although lesions ipsilateral
      to the TN were frequent occurrence; in these cases cerebellar system lesions may
      have produced ipsilateral vestibular nuclei disinhibition.

PMID- 1393507
TI  - Enduring dysmetria and impaired gain adaptivity of saccadic eye movements in
      Wallenberg's lateral medullary syndrome.
AB  - Saccadic eye movements and the adaptive control of their amplitudes were examined
      in patients with Wallenberg's lateral medullary syndrome. Half of the patients
      had permanent saccadic dysmetria. Their primary saccades had asymmetric
      amplitudes: those made in response to an ipsilateral target step (i.e. to the
      lesion side) tended to be hypermetric and saccades made in response to a
      contralateral target step were strongly hypometric. Multiple correction saccades
      were needed for target fixation. The adjustment of the amplitude of artificially
      induced hypermetric saccades, called gain adaptivity, was examined experimentally
      by using double target steps. The first target step elicited the primary saccade
      which triggered a further target displacement. This second, intra-saccadic target
      displacement was opposite to the first target step and caused the primary saccade
      to overshoot the final target position. In this way a post-saccadic target
      position error was generated which had to be corrected for foveal fixation. With
      repetition of this stimulus sequence the saccadic control system of normal
      subjects made an adjustment in amplitude of the main saccade such that the
      overshooting gradually diminished. After a few hundred trials primary saccades
      became orthometric with respect to the final target position; in respect to the
      first target step they were, however, strongly hypometric. The experimental data
      show that patients with Wallenberg's syndrome had a reduced capability to
      readjust saccadic amplitude. This observation together with the enduring saccadic
      dysmetria suggest that adaptive gain control of saccades is impaired in patients
      with lesions restricted to the dorsolateral medulla. It is speculated that these
      lesions most likely disrupt olivo-cerebellar pathways which are believed to be of
      paramount importance in visuo-motor adaptation of the cerebellum.

PMID- 1393508
TI  - Abnormalities of predictive saccades in hemi-Parkinson's disease.
AB  - We studied reflexive and predictive saccades by direct current electro
      oculography in nine patients with mild hemi-Parkinson's disease (hemi-PD) and in
      16 age-matched controls. In five patients, the neurological syndrome was
      predominant on the right side of the body (RPD) and in four patients, on the left
      side (LPD). Reflexive saccades were elicited in response to the random appearance
      (timing and location) of a light-emitting diode (LED). Predictive saccades were
      elicited by alternatively illuminating LEDs at 10 degrees right and left, at
      various fixed frequencies (0.25-1 Hz). In the reflexive task, latency and
      amplitude of the saccades were normal in both PD groups. In the predictive task,
      mean saccade latency was not significantly different between patients and normals
      but there were two significant abnormalities in timing: first, but only in LPD, a
      directional asymmetry in latency (left greater than right, e.g. at 0.25 Hz, mean
      difference of 90 ms); secondly, especially in RPD, an abnormal tracking pattern,
      reflected by more variability of the mean value (for each group of patients) of
      saccade latency at each point in time, throughout a period of tracking at a given
      frequency. Predictive saccades were also strongly hypometric in both PD groups
      but especially in LPD (e.g. for rightwards saccades: controls = 19 degrees, SD =
      1.6; LPD = 14 degrees, SD = 2.7; RPD = 15.7 degrees, SD = 2.3). These defects in
      saccadic timing and amplitude during predictive tracking were most salient at low
      frequencies. While these defects were largely bilateral, our findings suggest
      slightly different contributions of the right and left cerebral hemispheres to
      the spatial and timing components, respectively, that comprise optimal predictive
      saccadic behaviour.

PMID- 1393509
TI  - Relationship between electromyographic activity and clinically assessed rigidity
      studied at the wrist joint in Parkinson's disease.
AB  - The electromyographic (EMG) patterns recorded from wrist muscles during manually
      applied, repetitive flexion and extension movements of the wrist joint, used for
      simultaneous clinical assessment of rigidity, were studied in patients with
      Parkinson's disease and healthy subjects. Recordings were made whilst
      patients/subjects attempted voluntarily to relax the muscle of the arm whose
      wrist joint was manipulated. Individual patients were investigated before and at
      varying times after their routine daily medication as their clinical rigidity
      underwent associated modulations. It was often possible to induce additional
      alterations in clinical rigidity by instructing patients to perform an activation
      or Jendrassik-like manoeuvre (clenching the contralateral fist). In rigid
      patients, the approximately sinusoidal wrist displacements (60 deg, 1-1.5 Hz)
      typically elicited pronounced, cyclic modulations of EMG activities in wrist
      flexors and extensors; increases in EMG activity were phase-locked to the
      respective periods of muscle stretch. Stretch-related EMG activity reduced or
      disappeared as rigidity was abolished by drug therapy. The EMG patterns of
      patients showing cogwheel rigidity featured discrete, phasic bursts superimposed
      upon more generalized stretch-related increases in activity. In healthy subjects,
      showing no clinical rigidity, the pronounced cyclic modulations of EMG activity
      characteristic of rigid patients were absent during similar manually applied
      wrist displacements. Quantitative EMG measurements for individual patients, made
      'on' and 'off' medication and as their rigidity fluctuated, indicated that mild
      (grade 1) and moderate (grade 2) rigidity was consistently associated with
      increased stretch-related activity compared with non-rigid conditions. Pair-wise
      statistical analysis indicated such increases in EMG to be significant.
      Similarly, the ratios of EMG activities in the stretched versus released muscles
      were significantly greater for grades 1 and 2 rigidity than in the absence of
      rigidity. Overall, the present findings support the view that enhancement of
      stretch reflex activity has a major role in the genesis of parkinsonian rigidity.

PMID- 1393510
TI  - The auditory startle response in the Steele-Richardson-Olszewski syndrome and
      Parkinson's disease.
AB  - The startle response to an unexpected auditory stimulus was studied in eight
      patients with a clinical diagnosis of the Steele-Richardson-Olszewski syndrome
      (SRO), 11 patients with idiopathic Parkinson's disease (PD) and 12 normal
      subjects. The patients with PD were studied 'on' at the time of maximal effect of
      their treatment; five of these patients were also studied in their 'off' state
      without treatment. The auditory startle response was absent in three patients
      with SRO: in the remaining five the latency to onset of earliest electromyography
      activity (EMG) of the auditory startle response was delayed and few muscles
      (orbicularis oculi, sternocleidomastoid and rectus abdominis) were recruited in
      the response. In PD the auditory startle response was similar to that recorded in
      normal subjects, both in terms of the pattern of muscles recruited and the
      amplitude of the EMG responses, but the latency of responses in orbicularis oculi
      and sternocleidomastoid muscles were significantly delayed. This result was not
      influenced by treatment with L-dopa. In patients with SRO the finding of an
      abnormal startle response is consistent with loss of neurons in the lower pontine
      reticular formation. This region is intimately involved in the startle response
      in animal studies. In patients with PD the late auditory startle response might
      be related to withdrawal of facilitatory input to brainstem centres and
      reticulospinal pathways from basal ganglia. The similarity of the responses in
      patients when 'on' and 'off' suggests these pathways are not under potent
      dopaminergic control.

PMID- 1393511
TI  - Characterization of contralateral torques during static hip efforts in healthy
      subjects and subjects with hemiparesis.
AB  - Contralateral torques exerted at the hip were measured in healthy subjects and
      subjects with hemiparesis performing unilateral static hip efforts in abduction,
      adduction, flexion and extension, in a sitting position, at two torque levels. In
      general, the ipsilateral hip efforts were accompanied by mirrored contralateral
      torques in both groups of subjects. The directionality of these contralateral
      torques indicates that their action at the pelvis is mechanically opposite to the
      ipsilateral efforts, suggesting that they ensure the stabilization of the pelvis.
      In healthy subjects, analyses of variance showed no difference in the magnitude
      of the contralateral torques with regard to which limb was used to perform the
      task. However, a significant increase in magnitude was demonstrated in the
      contralateral torques concurrent with the increasing level of effort requested
      ipsilaterally. In hemiparetic subjects, when performing the tasks with their
      paretic limb, the magnitude of the contralateral torques was significantly
      increased in the non-paretic limb when compared with those measured in the
      paretic limb during non-paretic limb efforts. Based on the present results, a
      model of postural control is presented to explain the relationship between the
      ipsilateral and contralateral torques. Using this model, it is hypothesized that
      the increased contralateral torques observed in hemiparetic subjects when
      performing the tasks with their paretic limb is related to the weakness of the
      paretic muscles. The clinical importance of exercises used for the re-education
      of the paretic lower limb in this population, which consist of resisting the non
      paretic hip movements in order to strengthen the paretic hip muscles, is
      discussed in light of these results.

PMID- 1393512
TI  - Dorsal horn and dorsal column dysfunction in intramedullary cervical cord
      tumours. A somatosensory evoked potential study.
AB  - Median and tibial nerves somatosensory evoked potentials (SEPs) were recorded in
      20 patients with intramedullary cervical spinal cord tumours. The longitudinal
      extent of the tumour was determined by magnetic resonance imaging (MRI) and the
      surgeon's intraoperative observations. Somatosensory evoked potentials to median
      or tibial nerve stimulation were abnormal in 85% of patients. Three groups were
      identified on the basis of the median nerve SEP findings: Group I (20% of cases)
      with normal SEPs responses; Group II (30% of cases) with impaired cervical dorsal
      horn postsynaptic activity (abnormal N13 potential) but preserved dorsal columns
      transmission up to the cortex (normal P14 and N20 potentials); Group III (50% of
      cases) where the dorsal horn activity and dorsal columns transmission were both
      impaired. The isolated abolition of the N13 potential observed in Group II
      reflects a functional dissociation between segmental dorsal horn and dorsal
      columns structures and should prompt myelographic investigations. Postoperative
      follow-up suggests that absent N13, P14 and N20 potentials before surgery carry
      an ominous functional prognosis. However, postoperative recovery of the N13
      potential was found to occur in a few cases, suggesting that these tumours do not
      necessarily produce irreversible damage to the cervical dorsal horn neurons. Thus
      SEPs proved to have a high sensitivity in detecting cervical spinal cord
      dysfunction in intramedullary tumours, provided that a selective recording of the
      N13 potential is performed using a cervical-supraglottal derivation.

PMID- 1393513
TI  - Viliuisk encephalomyelitis in the Iakut people of Siberia.
AB  - Viliuisk encephalomyelitis (VE), a progressive neurological disorder with a fatal
      outcome usually in several months to 6 yrs after disease onset, is seen only
      among the Iakut people of Siberia. The acute meningoencephalitic phase of the
      disease is followed by progressive dementia, rigidity and spastic tetraparesis.
      The disease is characterized by multiple micronecrotic foci with marked
      inflammatory reactions and gliosis in the grey matter. The acute febrile onset,
      with cerebrospinal fluid (CSF) pleocytosis and increased protein in the CSF, the
      epidemiology and the inflammatory neuropathology suggest the disease is
      infectious. Studies on household spread indicate an incubation time of up to
      several years. Viliuisk encephalomyelitis was restricted to an ethically distinct
      group of Iakut people of the Middle Viliui region, but in recent decades, with
      migration from this region, it has been spreading into previously unaffected
      Iakut populations. The occurrence of multiple VE cases in households and
      introduction of the disease by migrants into new populations indicate horizontal
      transmission in a setting of long intimate contact.

PMID- 1393514
TI  - Occurrence of a multiple sclerosis-like illness in women who have a Leber's
      hereditary optic neuropathy mitochondrial DNA mutation.
AB  - Eight women are described who presented with bilateral, usually sequential, optic
      neuropathy, six of whom later developed a neurological syndrome indistinguishable
      from multiple sclerosis (MS). Magnetic resonance imaging, performed in five of
      the patients with an MS-like illness and in the two others with optic neuropathy
      alone, showed widespread white matter lesions as seen in MS. All of these women
      had matrilineal relatives with Leber's hereditary optic neuropathy, although this
      was not always apparent at presentation, and the most common mitochondrial DNA
      mutation associated with this disorder was detected in each of the women and
      their affected relatives. On the basis of observations made in these patients,
      the clinical features of Leber's hereditary optic neuropathy in males, and
      evidence for mitochondrially encoded peptides involved in the immune response in
      rodents, we propose that optic nerve damage in this disease could be
      immunologically mediated and that mitochondrial genes may contribute to
      susceptibility to MS.

PMID- 1393515
TI  - Treatment of experimental NADH ubiquinone reductase deficiency with menadione.
AB  - Chronic administration of diphenylene iodonium (DPI) to rats has been shown to
      model the characteristics of mitochondrial myopathy. Using this model the
      efficacy of menadione therapy has been assessed. Menadione treatment of rats
      injected with DPI was associated with improved weight gain and increased survival
      rate. This was accompanied by an improvement in muscle function as judged by
      analysis of isometric twitch tension of the gastrocnemius muscle (1 Hz for 20
      min). The decline in phosphocreatine (PCr) levels in the gastrocnemius muscle
      during stimulation and delayed recovery in PCr after stimulation were similar in
      the menadione treated and untreated models. Menadione treatment of the DPI model
      resulted in a resting intramuscular pH significantly lower than control or
      untreated DPI rats, but a similar decline in intramuscular pH to the DPI rats
      during stimulation. The changes in metabolite levels were broadly similar in both
      the menadione treated and untreated DPI models following stimulation, although
      the changes, except for increased lactate concentration, were generally less
      marked in the menadione-treated DPI model.

PMID- 1393516
TI  - Afferent and efferent connections of the bullfrog medial pallium.
AB  - Horseradish peroxidase or tritiated proline was unilaterally injected into the
      medial pallium in bullfrogs in order to determine the sources of afferent
      projections to the medial pallium and the targets of pallial efferent
      projections. Some cells in all telencephalic centers, except the corpus striatum
      and the pars lateralis of the amygdala, project to the ipsilateral medial
      pallium. The medial pallium receives projections from fewer centers in the
      contralateral hemisphere, which include the medial septal nucleus, the pars
      medialis of the amygdala, the bed nucleus of the pallial commissure and the
      medial pallium. The raphe nucleus and the anterior thalamic nuclei appear to be
      the only sources of afferents to the medial pallium from outside the
      telencephalon. Efferents of the medial pallium are far more extensive than
      reported in earlier studies. The medial pallium projects ipsilaterally to all
      telencephalic nuclei, with the exception of a large part of the corpus striatum,
      and contralaterally to the medial septal nucleus, the olfactory tubercle,
      amygdala, medial pallium and bed nucleus of the pallial commissure. Extensive
      efferent projections also terminate in preoptic and hypothalamic regions, as well
      as in most thalamic relay nuclei, the pretectum and, possibly, the optic tectum.
      Similarities to the medial pallium in other tetrapods and to that in mammals
      suggest that the medial pallium in anurans is homologous to the subicular and CA
      fields and, possibly, the dentate gyrus in mammals. However, the extensive
      projections of the medial pallium to the dorsal thalamus and pretectum in anurans
      may be primitive features of the medial pallium retained in anurans, or uniquely
      derived features in anurans.

PMID- 1393517
TI  - Sexual behavior and 2-deoxyglucose uptake in male red-sided garter snakes
      (Thamnophis sirtalis parietalis).
AB  - The [14C]2-deoxyglucose (2-DG) technique was used to study patterns of neural
      activity associated with the species-typical courtship behavior of male red-sided
      garter snakes (Thamnophis sirtalis parietalis). Males in this species court
      females intensely during the first month following spring emergence from their
      prolonged winter hibernation. Autoradiographic methods were used to measure the
      accumulation of radioactive label in various regions through the brains of male
      garter snakes that courted females, males that failed to court females, and males
      not exposed to females. Male garter snakes that actively courted females showed a
      pronounced increase in 2-DG accumulation, and therefore presumably neural
      activity, in the region of the anterior hypothalamus/preoptic area, relative to
      males that did not actively court females. Males exposed to females (regardless
      of whether they courted or not) showed widespread, non-specific increases in 2-DG
      uptake relative to males not exposed to females. The results indicate the utility
      of the 2-DG technique for studying complex, species-typical behaviors in
      vertebrates.

PMID- 1393518
TI  - The forebrain of the Pacific hagfish: a cladistic reconstruction of the ancestral
      craniate forebrain.
AB  - The forebrain of the Pacific hagfish is described with regard to its morphology,
      cytoarchitecture, and secondary olfactory projections. The forebrain ventricular
      system is greatly reduced in adult hagfishes, although vestiges of ventricular
      structures can still be recognized. In order to clarify topographical
      relationships within the forebrain, we provide a three-dimensional reconstruction
      of the ventricular system, including the vestigial portions. Topography and
      embryology lead us to conclude that the 'primordium hippocampi' of previous
      authors is a diencephalic structure. For topographical and hodological reasons,
      we interpret the 'area basalis' of previous authors to be part of the preoptic
      region, and we identify a part of the so-called 'nucleus olfactorius anterior' as
      the homologue of the striatum. The laminated pallium is dominated by secondary
      olfactory projections and shows a high degree of regional cytoarchitectural
      specialization, as does the entire forebrain. In all, 42 cell groups are
      identified in the forebrain of hagfishes (compared to only about 25 in lampreys,
      for example). This surprisingly high degree of cytoarchitectural complexity
      prompted us to re-examine the phylogenetic history of craniate brains with this
      complexity in mind. In this paper we use cladistic methodology to reconstruct a
      morphotype, and we conclude that the forebrains of the earliest craniates may
      have been more complex than previously believed. This reconstruction includes
      hypotheses regarding the general morphology, secondary olfactory system, and
      visual system, as well as the relative sizes of major divisions of the forebrain
      in the earliest craniates.

PMID- 1393519
TI  - Speech production, syntax comprehension, and cognitive deficits in Parkinson's
      disease.
AB  - Speech samples were obtained that were analyzed for voice onset time (VOT) for 40
      nondemented English speaking subjects, 20 with mild and 20 with moderate
      Parkinson's disease. Syntax comprehension and cognitive tests were administered
      to these subjects in the same test sessions. VOT disruptions for stop consonants
      in syllable initial position, similar to those noted for Broca's aphasia,
      occurred for nine subjects. Longer response times and errors in the comprehension
      of syntax as measured by the Rhode Island Test of Sentence Comprehension (RITLS)
      also occurred for these subjects. Anovas indicate that the VOT overlap subjects
      had significantly higher syntax error rates and longer response times on the
      RITLS than the VOT nonoverlap subjects--F(1, 70) = 12.38, p less than 0.0008;
      F(1, 70) = 7.70, p less than 0.007, respectively. The correlation between the
      number of VOT timing errors and the number of syntax errors was significant. (r =
      0.6473, p less than 0.01). VOT overlap subjects also had significantly higher
      error rates in cognitive tasks involving abstraction and the ability to maintain
      a mental set. Prefrontal cortex, acting through subcortical basal ganglia
      pathways, is a component of the neural substrate that regulates human speech
      production, syntactic ability, and certain aspects of cognition. The
      deterioration of these subcortical pathways may explain similar phenomena in
      Broca's aphasia. Results are discussed in relation to "modular" theories.

PMID- 1393520
TI  - Phonological error analysis, development and empirical evaluation.
AB  - A method of error analysis, designed to examine phonological and nonphonological
      reading and spelling processes, was developed from preliminary studies and
      theoretical background, including a linguistic model and the relationships
      between articulatory features of phonemes. The usefulness of this method as an
      assessment tool for phonological ability was tested on a group of normal
      subjects. The results from the error analysis helped clarify similarities and
      differences in phonological performance among the subjects and helped delineate
      differences between phonological performance in spelling (oral and written) and
      reading within the group of subjects. These results support the usefulness of
      this method of error analysis in assessing phonological ability. Also, these
      results support the position that phonological approximation of responses is an
      important diagnostic feature and merely cataloging errors as phonologically
      accurate or inaccurate is inadequate for assessing phonological ability.

PMID- 1393521
TI  - Auditory event related potentials during lexical categorization in the oddball
      paradigm.
AB  - Event related potentials (ERPs) and reaction times (RTs) were recorded from 18
      subjects, performing lexical categorization of words and nonwords. Three sets of
      monosyllable utterances, differentiated in semantic and rhyming attributes, were
      presented using the "oddball paradigm." ERPs included a sustained negativity
      which began approximately 100 msec after stimulus onset and peaked at
      approximately 400 mses (SN4) poststimulus, in response to target as well as to
      nontarget word stimuli. Semantic effects on SN4 latency were observed only for
      target utterances. Nonmeaningful word targets were associated with longer SN4
      peak latencies as well as slower RTs compared to meaningful word targets. It is
      suggested that these longer latencies are due to a longer time required for an
      exhaustive search in permanent memory before categorizing a stimulus as a
      nonmeaningful word.

PMID- 1393522
TI  - A computational account of deep dysphasia: evidence from a single case study.
AB  - We present a case study of a patient, NC, who demonstrates the defining
      characteristics of deep dysphasia including semantic errors in repetition and an
      inability to repeat nonwords. In addition, NC's single word repetition and
      lexical decision performances are influenced by the imageability of the word
      input. NC also demonstrates a severely restricted phonological short-term memory
      (one digit, one word). Although his phonological discrimination is good in a
      minimal pairs judgment task, it becomes impaired when a delay is imposed or
      rehearsal is prevented between presentation of each member of a pair. NC's output
      is fluent but contains many formal paraphasias and neologisms. NC's total
      language profile is evaluated within the framework of Dell's (1986) interactive
      spreading activation model of language production. Adapting this output model to
      input processes, we account for all of NC's deep dysphasic symptoms as well as
      his pattern of production in a way that is more parsimonious than other attempts
      to model this disorder. In particular, we suggest that the semantic and formal
      paraphasias in naming and repetition result from a pathological increase in the
      rate of decay of primed nodes in the semantic-lexical-phonological network. This
      rapid decay increases the probability that phonologically and/or semantically
      related lexical nodes primed by top-down and bottom-up feedback during the
      operation of lexical activation and retrieval will be activated and selected
      instead of the lexical target. The advantages of using this model to account for
      aphasic symptoms and the implications for other lexical theories are discussed.

PMID- 1393523
TI  - Lexical tones in Thai after unilateral brain damage.
AB  - An acoustic perceptual investigation of the five lexical tones of Thai was
      conducted to evaluate the nature of tonal disruption in patients with unilateral
      lesions in the left and right hemisphere. Subjects (n = 48) included 10 young
      normal adults, 10 old normal adults, 11 right hemisphere nonaphasics, 9 left
      hemisphere fluent aphasics, and 8 left hemisphere nonfluent aphasics. The five
      Thai tones (mid, low, falling, high, rising) were produced in isolated
      monosyllables, presented for tonal identification judgments, and measured for
      fundamental frequency (Fo) and duration. Results of an analysis of variance
      indicated that left hemisphere nonfluent speakers signaled and tonal contrasts at
      a lower level of proficiency. The extent of their impairment varied depending on
      severity level of aphasia. When compared to normal speakers, tonal identification
      for less severe nonfluent aphasics differed more in degree than in kind, and for
      more severe nonfluent aphasics differed both in kind and in degree. Acoustic
      analysis revealed that with the exception of one left nonfluent, average Fo
      contours were comparable in shape across speaker groups. Variability in Fo
      production, however, was greater in left nonfluent speakers than in any of the
      other four groups of speakers. Issues are discussed regarding the extent and
      nature of tonal disruption in aphasia and hemispheric specialization for tone
      production.

PMID- 1393525
TI  - The verbal transformation effect: auditory illusions as an index of lexical
      processing and homolog activation.
AB  - A technique of inducing auditory illusions was used so that 192 undergraduates
      heard through headphones either three asynchronous dichotic versions of the same
      repeating word, at each of three auditory locations (left, center, and right), or
      only one single repeating word, monaurally or diotically, at each location.
      Independent illusory changes at each location were reported. Subjects' reports of
      lexical illusions, but not nonlexical illusions, were fewer at the right ear for
      three- vs. one-signal listening. These results support the homolog activation
      hypothesis (Boles, 1990) in which disruption of interhemispheric communication
      occurs for the hemisphere least capable of processing lexical information. In the
      current experiment homolog activation led to loss of lexical information when
      received from auditory positions other than the right, when three signals are
      presented. Lexical illusions (Verbal Transformations) may be the result of the
      misapplication of lexical knowledge in an ambiguous situation, listening to a
      recycling word without stabilizing syntactic or semantic context.

PMID- 1393524
TI  - Dysnomia in Alzheimer's disease: an evaluation of neurobehavioral subtypes.
AB  - The relative influence of perceptual and semantic features on naming performance
      was investigated with reference to the neurobehavioral profiles displayed by
      patients with Alzheimer's disease (AD). Forty-one patients were classified as
      manifesting a verbal, visual, or global subtype based upon their pattern of
      neuropsychological functioning. Perceptual characteristics of to-be-named
      pictures were varied by manipulating the amount of line detail, whereas semantic
      qualities were varied by altering word frequency norms. All AD subtypes were less
      accurate than normal elderly controls in naming low frequency pictures. Patients
      and controls took longer to name low frequency and high complexity pictures, and
      this effect was comparable across the AD groups. Patients with predominantly
      visual deficits were significantly slower in naming than controls, and those with
      verbal impairments made a higher proportion of semantic naming errors when
      compared to patients displaying visual or severe global impairments. These
      results suggest that deficits in semantic processing contribute to naming
      dysfunction in AD, and they highlight the importance of examining dissociations
      among neurobehavioral subtypes.

PMID- 1393527
TI  - Cerebral asymmetry for speech and the asymmetry in path lengths for the right and
      left recurrent nerves.

PMID- 1393526
TI  - Slowed lexical access in nonfluent aphasia: a case study.
AB  - A list priming paradigm (LPP) was used to examine the hypothesis that nonfluent
      aphasics are literally slowed down in automatic access to lexical information. In
      this paradigm, words are presented visually, and the subject's task is to make a
      lexical decision on each word as quickly as possible after its presentation. As
      soon as a lexical decision is made on one word, that word is removed and, after a
      predetermined interword interval, the next word is presented. In this way, a
      continuous "list" effect is obtained. Prior studies with both college-age and
      elderly subjects using the LPP have shown that, independently of age, on the LPP,
      priming obtains at interword delays of 500 to 800 msec, but not at either shorter
      or longer interword delays. In the study reported here, the LPP was used to
      examine delays at which priming obtained for LD, a nonfluent aphasic with a
      lesion primarily in the left frontal region. Examining interword delays ranging
      from 500 to 1800 msec, the subject showed priming only at a delay of 1500 msec, a
      considerably longer delay than that at which neurologically intact subjects have
      shown priming. Based on these results, it is argued that while automatic access
      is retained, that access is much slower in a nonfluent aphasic than in
      neurologically intact elderly subjects. These results are discussed in terms of
      how slowed lexical access might impact on discourse comprehension.

PMID- 1393528
TI  - Stabilization of acetylcholine receptors at the neuromuscular synapse: the role
      of the nerve.
AB  - The majority of acetylcholine receptors (AChRs) at innervated neuromuscular
      junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent
      muscles. In addition to the stable AChRs, approximately 18% of AChRs at these
      innervated junctions are rapidly turned over (RTOs), with half lives of less than
      24 h. We have postulated that RTOs may be precursors of stable AChRs, and that
      the motor nerve may influence their stabilization. This hypothesis was tested by:
      (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii)
      denervating one SM muscle in each mouse, and (iii) following the fate of the
      labeled AChRs through a 5-day period when RTOs were either stabilized or
      degraded. The hypothesis predicts that denervation should preclude stabilization
      of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The
      results showed a highly significant (P less than 0.002) deficit of stable AChRs
      in denervated as compared with innervated muscles. Control experiments excluded
      the possibility that this deficit could be attributed to independent accelerated
      degradation of either RTOs or pre-existing stable AChRs. The observed deficit was
      quantitatively consistent with the deficit predicted by a mathematical model
      based on interruption of stabilization following denervation. We conclude that:
      (i) the observed deficit after denervation of NMJs is due to failure of
      stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are
      precursors of stable AChRs; (iii) stabilization occurs after the insertion of
      AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs.
      The concept of receptor stabilization has important implications for
      understanding the biology of the neuromuscular junction and post-synaptic
      plasticity.

PMID- 1393529
TI  - Osmotic stimulation differentially affects cellular levels of corticotropin
      releasing hormone and neurotensin/neuromedin N mRNAs in the lateral hypothalamic
      area and central nucleus of the amygdala.
AB  - To investigate the effects of osmotic stimulation on neural circuits concerned
      with non-neuroendocrine aspects of homeostatic regulation, the levels of the
      mRNAs coding for corticotropin-releasing hormone (CRH) and neurotensin/neuromedin
      N (NT/NMN) in the lateral hypothalamic area (LHA) and central nucleus of the
      amygdala (CEA) of animals given 2.5% saline to drink overnight were measured
      semiquantitatively using in situ hybridization. Overnight osmotic stimulation
      leads to converse effects on the levels of these two mRNAs in different
      anatomical regions; increased levels of both mRNAs are seen in the LHA, but
      levels decrease in the CEA. While a number of previous studies have shown that
      ppCRH mRNA in the paraventricular (PVH) and supraoptic (SO) nuclei of the
      hypothalamus may contribute to the neuroendocrine response to osmotic
      stimulation, the present results show that in response to osmotic stimulation
      neurons located outside the PVH and SO may also modulate their synthetic
      potential, not just for CRH but also NT/NMN. These results suggest that a
      physiological stimulus may modulate the levels of two peptides previously
      identified in circuits projecting from the forebrain to nuclei in the brainstem,
      and as such, CRH and NT/NMN may participate in the regulation by the forebrain of
      the autonomic and/or behavioral responses of the animal to dehydration.
      Furthermore, these data show that a particular stimulus has opposite effects on
      the level of both peptide mRNAs when expressed in two different cell groups,
      suggesting first, that these peptides may have more than one role in the
      response, and second, the existence and influence of differential control
      mechanisms.

PMID- 1393530
TI  - Regional differences in the regulation of dopamine and noradrenaline release in
      medial frontal cortex, nucleus accumbens and caudate-putamen: a microdialysis
      study in the rat.
AB  - Dopamine (DA) and noradrenaline (NA) extracellular levels have been measured by
      microdialysis in the medial frontal cortex (MFC), nucleus accumbens (NAc) and
      caudate-putamen (CP) under baseline conditions in awake and halothane
      anaesthetized rats, and after application of three types of stimuli which are
      likely to activate the brainstem catecholaminergic systems: mild stressors
      (handling and tail pinch), rewarded behavior (eating palatable food without prior
      food deprivation) and electrical stimulation of the lateral habenular nucleus.
      Changes were studied with and without uptake blockade (10 microM nomifensine in
      the perfusion fluid). The influence of calcium concentration (1.2 or 2.3 mM in
      the perfusion fluid) on DA and NA overflow was tested in some cases. Handling and
      tail pinch stimulated both DA and NA overflow in MFC, and enhanced NA overflow in
      NAc. By contrast, these mildly stressful stimuli had only marginal effects on DA
      overflow in NAc and no effects on either DA or NA overflow in CP. Eating behavior
      was accompanied by increased DA and NA overflow in MFC but had no effect in NAc.
      These regional differences were similar also when the manipulations were applied
      under uptake blockade, which indicates that the more pronounced changes seen in
      MFC did not simply reflect a more sparse innervation (i.e. lower density of
      uptake sites) in the MFC compared to the more densely innervated NAc and CP
      areas. Stimulation of the lateral habenula induced a 2-3-fold increase in NA
      overflow in both MFC, NAc and CP but had no consistent effect on DA overflow in
      any region. The effect on NA release was abolished by a transection of the
      ipsilateral fasciculus retroflexus (which carries the efferent output of the
      lateral habenula). The results show that the forebrain DA and NA projections to
      cortical and striatal targets are differentially regulated during ongoing
      behavior, that the mesocortical and mesostriatal DA systems respond quite
      differently to stressful and rewarding stimuli; and that the NA projection to MFC
      (like the dopaminergic one) is more responsive to stressful and rewarding stimuli
      than the ones innervating the striatum (NAc and CP). The results support the view
      that environmental stimuli evoking emotional arousal (whether aversive or non
      aversive) are accompanied by increased DA and NA release above all in the MFC and
      only to a minor extent in limbic and striatal areas.

PMID- 1393531
TI  - Sex differences in the binding of type I and type II corticosteroid receptors in
      rat hippocampus.
AB  - Binding parameters of soluble Type I and Type II receptors were assessed in
      hippocampus of adult, adrenalectomized, male and female rats. No sex differences
      in the number of either Type I or Type II receptors could be demonstrated between
      gonadally intact animals. When females treated with 17 beta-estradiol benzoate
      (10 micrograms/day) were compared with males, a statistically significant
      reduction in Type II receptors was observed in the females; progesterone produced
      no further decrease in receptor numbers. The amount of tissue-associated
      corticosteroid-binding globulin in gonadally intact animals (perfused with
      dextran-saline) was twice as great in females as males. Sex-dependent differences
      in these gonadally intact rats were found in the affinity, measured as the
      dissociation constant (Kd), of both the Type I and Type II receptors. For both
      receptors, affinity in cytosols from females was reduced. The difference for the
      Type II receptor was slight, but the Kd value of the Type I receptor was several
      fold higher in females. The difference in affinity was evident with both natural
      and synthetic steroid ligands. There appears to be little, if any, difference in
      affinity between the hippocampal Type I and the Type II receptors in females.
      This suggests that the occupancy of Type I receptors in females is substantially
      less than that of males at low circulating concentrations of corticosteroids.

PMID- 1393532
TI  - SDN-MPOA volume in male rats is decreased by prenatal stress, but is not related
      to ejaculatory behavior.
AB  - A computer-assisted image analysis technique was used to measure the adult volume
      of the sexually dimorphic nucleus of the medial preoptic area (SDN-MPOA) in
      prenatally stressed male rats and in groups of non-stressed males and females.
      The SDN-MPOA of male offspring from dams stressed daily (i.e. three 45-min
      exposures to physical restraint and bright light) during the last week of
      pregnancy was significantly smaller than in males not exposed to stress, but was
      larger than in females. Maternal stress has been shown to attenuate the surge in
      fetal plasma testosterone (T) which normally occurs on days 18 and 19 of
      gestation in male rats. The present results suggest that suppression of T during
      prenatal development leads to an incomplete masculinization of the SDN-MPOA in
      male rats. There was no difference in SDN-MPOA volume between males that
      exhibited the ejaculatory pattern when tested with estrous females and males that
      failed to ejaculate in either the control or prenatal stress group. SDN-MPOA
      volume does not appear to be predictive of masculine ejaculatory performance.

PMID- 1393533
TI  - Discharge response of cerebellar Purkinje cells to stimulation of C-fiber in cat
      saphenous nerve.
AB  - Experiments were performed in cats under chloralose anaesthesia and immobilized
      by Flaxedil. The discharge responses of cerebellar Purkinje cells (PC) were
      recorded with a microelectrode. The spontaneous activities of PC consisted of
      simple spike (SS) and complex spike (CS). When the saphenous nerve was stimulated
      at a low intensity, which elicited the A-fiber input only, the discharge
      responses (A-CED) consisted of an early component with short latency and late
      component with long latency in PC-SS and PC-CS. After A-fibers were blocked
      selectively by the polarizing current, the stimulation at the strength of C-fiber
      suprathreshold evoked the characteristic responses (C-CED) of PC-SS and PC-CS
      with middle latency. However, the C-CED could not be evoked by the inputs of A-
      and C-fibers simultaneously. These results suggested that the pure C-fiber input
      reaching the cerebellar PC passed through not only climbing fibers, but also
      mossy fibers, and elicited the characteristic responses (C-CED); these responses
      were neither the early component nor late component of the A-CED. When A- and C
      fiber were activated at the same time, the C-CED might be inhibited by the A
      fiber inputs.

PMID- 1393534
TI  - Cerebellar neurons and glia respond differentially to endothelins and sarafotoxin
      S6b.
AB  - Endothelins (ETs) and sarafotoxin-S6b belong to a family of extremely potent
      vasoconstrictors which may also have a role as neuropeptides or neuromodulators
      in the central nervous system (CNS). We show, using single cell dynamic video
      imaging of intracellular free calcium ions ([Ca2+]i), that binding of ET to its
      receptors modulates [Ca2+]i of neurons as well as glial cells in primary cultures
      of rat cerebellum. At least two receptor subtypes, differing in both their ligand
      specificity and distribution, appear to be involved in the action of ETs and
      sarafotoxin S6b on these cells. One of these receptors may be a previously
      undescribed neuronal form of ET receptor. This is the first demonstration of a
      direct effect of ETs on neurons as well as glia in the CNS. These data support a
      possible role for ET as a neurotransmitter or neuromodulator in the CNS.

PMID- 1393535
TI  - Stimulation in the ventral posterior lateral nucleus of the primate thalamus
      leads to release of serotonin in the lumbar spinal cord.
AB  - Stimulation in the ventrobasal complex of the thalamus relieves neuropathic pain
      and inhibits spinal cord transmission of nociceptive information. Electrical
      stimulation of the ventral posterior nucleus of the thalamus elicited increases
      in extracellular serotonin concentration in the spinal cords of anesthetized
      monkeys. These results suggest that thalamic stimulation activates the raphe
      spinal tract and thus implicates serotonin as a mediator of thalamic stimulation
      induced analgesia.

PMID- 1393536
TI  - Inhibition of peptide release from invertebrate neurons by the protein kinase
      inhibitor H-7.
AB  - The protein kinase inhibitor H-7 has been shown to prevent the potentiation of
      action potentials that normally accompanies an afterdischarge in the bag cell
      neurons of Aplysia. We have now shown that H-7 attenuates the release of ELH from
      these neurons during an afterdischarge without influencing the firing frequency
      or length of the afterdischarge.

PMID- 1393538
TI  - Anisomycin and cycloheximide protect cerebellar neurons in culture from anoxia.
AB  - Protein synthesis inhibitors have recently been shown to protect from ischemia
      induced neuronal death in the rat hippocampus in vivo. In an attempt to further
      investigate the mechanism of neuronal death resulting from anoxia, cerebellar
      neurons grown in culture were exposed to an anoxic atmosphere in the presence of
      protein synthesis inhibitors. Anisomycin and cycloheximide (100 micrograms/ml)
      offered, respectively, a 97 +/- 4% and 26 +/- 13% protection against anoxia
      induced neuronal death.

PMID- 1393537
TI  - The effect of axon injury on microtubule-associated protein MAP2 mRNA in the
      hypoglossal nucleus of the adult rat.
AB  - High molecular weight microtubule-associated protein 2 (HW MAP2) is heavily
      concentrated in mature dendrites and may be critical for dendritic stability.
      Motor axon injury results in retraction of the dendritic tree which is associated
      with a decrease in MAP 2-like immunoreactivity (-LIR). Here we have shown with in
      situ hybridization that motor axon injury results in reduced expression of HW
      MAP2 mRNA in affected neurons. We conclude that axotomy induces a down-regulation
      of HW MAP2 synthesis.

PMID- 1393539
TI  - Electrophysiological evidence for reciprocal connectivity between the nucleus
      accumbens septi and ventral pallidal region.
AB  - Responses of nucleus accumbens (NAS) neurons to ventral pallidum (VP) stimulation
      were examined in anesthetized rats. Results demonstrated: (1) NAS to VP
      projection neurons reside primarily in the relatively lateral aspects of the NAS,
      and (2) substantial VP to NAS feedback also exists. These feedback projections
      are widely distributed throughout the NAS. Moreover, functionally identifiable
      NAS neuronal subpopulations were revealed by analysis of unit responses to
      concurrent VP and fimbria stimulation: (1) most, but not all NAS units responded
      to VP and fimbria stimulation in qualitatively divergent ways; (2) many NAS units
      demonstrated monosynaptic convergence of fimbria and VP terminations onto
      individual NAS units; and (3) in other cases, identified NAS-VP projection
      neurons were also monosynaptically activated by fimbria stimulation.

PMID- 1393540
TI  - The uptake of anionic and cationic amino acids by the isolated perfused sheep
      choroid plexus.
AB  - The carrier-mediated uptake of anionic and cationic amino acids by the
      basolateral face (blood side) of the isolated perfused sheep choroid plexus was
      demonstrated using the paired-tracer dilution technique. The uptake of these two
      classes of amino acid was higher than at the blood-brain barrier with no cross
      competition between them. In addition the uptake was markedly stereospecific with
      a high degree of selectivity and no interaction with the L-system amino acids.

PMID- 1393541
TI  - Characteristics of caudal ventrolateral medullary neurons antidromically
      activated from rostral ventrolateral medulla in the rabbit.
AB  - We made extracellular recordings from 107 spontaneously active neurons in the
      caudal ventrolateral medulla, after identifying the cells by antidromically
      activating them from the rostral ventrolateral medulla, in urethane-anesthetized
      rabbits. We tested the response of these neurons to inputs from baroreceptors and
      chemoreceptors. The median conduction velocity for antidromically activated
      neurons was 0.84 m/s. Raising blood pressure with intravenous noradrenaline
      excited 22% of 96 neurons tested, inhibited 61%, and had no effect on the
      remaining 17%. The spontaneous discharge rate of neurons excited by an increase
      in blood pressure was 1.6 +/- 0.3 spikes/s, lower than the discharge rate of
      neurons inhibited by this procedure (4.9 +/- 0.5 spikes/s). Excitation of
      chemoreceptors by hypoxia increased the discharge rate of 14/16 neurons tested in
      the group excited by baroreceptor inputs. In the group inhibited by baroreceptor
      inputs 21/35 neurons tested were excited and 12/35 neurons were inhibited by
      chemoreceptor inputs. Neurons excited by an increase in blood pressure were
      located in the previously defined caudal vasodepressor region and in a region
      just rostral to the obex, intermediate between the vasodepressor region and the
      rostral sympathoexcitatory region. These neurons may form part of the central
      inhibitory link in the baroreceptor-vasomotor pathway. Other antidromically
      activated neurons in the vasodepressor region may be inhibitory vasomotor cells
      with a function relatively independent of baroreceptor inputs, or they may be A1
      catecholamine neurons, with axons passing through the rostral medulla en route to
      the forebrain.

PMID- 1393542
TI  - Effects of central serotonin on autonomic control of heart rate in intact and
      baroreceptor deficient rats.
AB  - The intracerebroventricular (i.c.v.) injection of serotonin (5-HT) increases
      blood pressure and decreases heart rate (HR) in conscious rats by activation of 5
      HT2/1C receptors. Since the bradycardia is eliminated by pretreatment with a
      ganglionic or V1-vasopressin antagonist, we proposed that the decrease in HR
      results from an effect on cardiac autonomic activity which is potentiated by
      vasopressin. The present study aimed first, to further characterize mechanisms by
      which the i.c.v. injection of 5-HT (2.5 micrograms) decreases HR in conscious
      rats, and second to determine the cardiovascular responses to 5-HT (2.5
      micrograms, i.c.v.) in rats with chronic sinoaortic deafferentation (SAD). In
      intact rats, the bradycardia elicited by 5-HT was eliminated by a combination of
      the muscarinic antagonist atropine and the beta-adrenoceptor antagonist sotalol;
      neither antagonist was effective alone. In rats with SAD, 5-HT produced a larger
      increase in blood pressure and a marked tachycardia, both of which were
      eliminated by the 5-HT2/1C antagonist LY 53857. Furthermore, in rats with SAD the
      5-HT-induced increase in HR was blocked by sotalol alone. In conclusion, 5-HT
      (2.5 micrograms, i.c.v.) acts on central 5-HT2/1C receptors to increase arterial
      pressure. In intact rats this decreases HR by vasopressin-potentiated activation
      of baroreceptor reflexes and subsequent increase in vagal tone and decrease in
      cardiac sympathetic tone. In the absence of baroreflexes, a direct central effect
      of 5-HT to produce a beta-adrenoceptor-mediated cardioacceleration is unmasked.

PMID- 1393543
TI  - Development of long-term subsensitivity to GABA in dorsal raphe neurons of
      amygdala-kindled rats.
AB  - Previously we reported a long-term change in neuronal sensitivity to GABA
      following amygdala kindling. Dorsal raphe neurons of amygdala-kindled rats
      exhibited significant subsensitivity to GABA 4 weeks after the last fully
      generalized (Stage 5) seizure. We hypothesized that this alteration in GABA
      sensitivity might reflect neuronal changes corresponding to kindled seizure
      susceptibility and subsequent experiments have investigated this hypothesis. The
      progression towards neuronal subsensitivity to GABA during amygdala kindling can
      be correlated with the Stage to which an animal has been kindled. That is, when
      measured 4 weeks after the last kindled seizure, dorsal raphe neurons are
      supersensitive to GABA following a Stage 2 seizure, not different from controls
      following a Stage 3 seizure and subsensitive to GABA following a Stage 5 seizure.
      In addition, subsensitivity to GABA appears to be permanent in that it is still
      measurable 3 months after the last Stage 5 seizure. Thus, amygdala kindling
      produces long-term, perhaps permanent, changes in neuronal sensitivity to GABA
      and these changes reflect the Stage to which an animal has been kindled.

PMID- 1393544
TI  - Role of endogenous opioid peptides in the acute adaptation to hypoxia.
AB  - A non-lethal, hypoxic conditioning stimulus has been shown by Rising and D'Alecy
      to increase hypoxic survival time in mice. To determine if endogenous opioids
      alter the hypoxic conditioning-induced increase in hypoxic survival time, we
      administered naloxone (0.1, 1.0 mg/kg i.p.) or saline (0.3 ml i.p.) 5 min prior
      to conditioning. Sixty percent of the mice received the hypoxic conditioning
      stimulus consisting of three sequential hypoxic exposures (4.5% oxygen balance
      nitrogen for 1.5, 2 and 2.5 min) separated by 5 min of room air. The remaining
      mice did not receive hypoxic conditioning but instead remained in room air for
      this time. All mice were tested for hypoxic survival by first exposing them to 20
      s of 8.5% oxygen balance nitrogen followed by exposure to 4.5% oxygen balance
      nitrogen. The hypoxic survival time was recorded as the time from the onset of
      the 4.5% oxygen to the cessation of spontaneous ventilation. Naloxone (1 mg/kg)
      completely blocked the adaptation to hypoxia induced by hypoxic conditioning (P =
      0.003). Morphine (1, 5, 10 and 20 mg/kg) had no effect on hypoxic adaptation;
      however, 50 mg/kg morphine decreased the adaptation induced by conditioning (P
      less than 0.0001) possibly due to high dose toxicity. These data suggest that
      endogenous opioids are involved in the protective adaptation to hypoxia induced
      by prior exposure to non-lethal hypoxia.

PMID- 1393545
TI  - Different effects of intracellular and extracellular TEA on voltage-dependent K
      currents of acutely isolated hippocampal CA1 neurons.
AB  - Tetraethylammonium (TEA) effects on K currents were examined on either side of
      the membrane of hippocampal CA1 neurons by means of whole-cell voltage-clamp
      recording and intracellular perfusion. Recording media contained ion channel
      blockers to allow the selective activation of voltage-dependent K currents which
      consisted of a rapidly decaying component (A-current) and a delayed component.
      Voltage protocols were applied to separate the A-current from the delayed
      component. Results show that 10 mM extracellular TEA suppressed 50 +/- 11% (S.D.,
      n = 4) of the delayed current at different levels of depolarization but had
      little effect on the A-current. In contrast 10 mM TEA applied by intracellular
      perfusion suppressed the A-current by 42 +/- 10% (S.D., n = 4) in addition to
      inhibiting the delayed currently 55 +/- 15% (S.D., n = 4). Both the intracellular
      and extracellular actions of TEA on K currents showed no voltage- nor time
      dependency. The results suggest that voltage-dependent transient current (A
      current) is mediated through a separate group of ionic channels distinct from
      those that sustained the delayed current. Furthermore, the asymmetrical effects
      of intracellular and extracellular TEA on the transient current are similar to
      those described for the A-current in molluscan neurons. This observation supports
      the notion that the structure of the ion channel mediating the A-current is
      closely conserved across different species.

PMID- 1393546
TI  - Projections of anterior hypothalamic neurones to the dorsal and ventral
      periaqueductal grey in the rat.
AB  - Projections of neurones in the rostral hypothalamus to the periaqueductal grey
      matter (PAG) of the rat were investigated using retrograde tracing of red and
      green fluorescent latex microspheres. Microspheres were injected into one of 4
      PAG sub-divisions, namely the dorsal, dorsolateral, ventral and ventrolateral
      parts. The patterns of retrogradely labelled neurones in the hypothalamus from
      each of the 4 PAG sub-divisions were found to differ and these are described. The
      precise nature of projections of neurones in the anterior hypothalamic area (AHA)
      was investigated and it was found that neurones within a circumscribed area of
      AHA, the lateral area of the anterior hypothalamus (LAAH), projected
      predominantly to the dorsolateral PAG while neurones in immediately adjacent
      areas projected to either dorsolateral or ventrolateral aspects of the PAG.
      Double retrograde tracing studies, where the two different colour beads were
      injected into different subdivisions of the PAG, gave rise to very few double
      labelled hypothalamic neurones, indicating that neurones in the hypothalamus
      project to only one sub-division of the PAG. The functional significance of these
      pathways is discussed in relation to mechanisms of autonomic and sensory control.

PMID- 1393547
TI  - Feedback control of limb stiffness and scaled phase invariance properties of
      skilled high-speed arm flexion movements of a loaded manipulator.
AB  - In this and a previous experiment it has been observed that subjects produce
      innervation patterns (EMG) that are load specific, i.e., they produce
      concentration patterns for movements made with inertial loads and triphasic
      patterns for movements made with elastic loads. The protocol of these experiments
      prevented any adaptive responses to the load changes, therefore, it was assumed
      that pattern matching to load type was a real time updating response of the
      peripheral feedback systems. This updating response was assumed to be a mechanism
      for fine tuning the muscle torque by regulation of the mechanical impedance
      (stiffness) of the limb. Using a standard equation of motion, it was shown that
      the velocity is equal to the ratio of the muscle torque to the mechanical
      impedance. Substitution of this ratio for the ordinate of the scaled phase
      diagrams was then suggested as a real time updating mechanism to account for the
      scaled phase invariance recorded in this experiment and in the experiment
      reported by Ruitenbeek, J.C., Biol. Cybernetics 51 (1984) 11-20.

PMID- 1393548
TI  - A novel m2-selective muscarinic antagonist: binding characteristics and
      autoradiographic distribution in rat brain.
AB  - Although several m2-selective muscarinic antagonists have been described, they
      are not particularly potent. Thus, the development of potent m2-selective
      compounds remains an important goal. We now report that a bio-isoster of AQ-RA
      741 is both one order of magnitude more potent and slightly more selective than
      previously described compounds. DIBA, a di-benzo derivative of AQ-RA 741, in
      which the pyridine of the tricycle is replaced with a benzene ring, had Ki values
      of 4, 0.3, 11 and 2 nM at m1 through m4 receptors, respectively. These values
      were determined in competition studies with [3H]N-methylscopolamine ([3H]NMS) in
      membranes from transfected A9 L cells (m1 and m3), rat heart (m2) and NG108-15
      cells (m4). AQ-RA 741 had Ki values of 34, 4, 86 and 15 nM at each of these
      receptors. The autoradiographic distribution of DIBA binding sites was determined
      by competition studies of [3H]NMS in rat brain. At low concentration, DIBA
      reduced [3H]NMS binding most significantly from superior colliculi, thalamus,
      hypothalamus, pontine nucleus, and interpeduncular nucleus, and not appreciably
      from caudate nucleus, cerebral cortical regions, or hippocampus, consistent with
      its binding to m2 receptors. These data indicate that DIBA is the most potent, m2
      selective muscarinic antagonist yet described. DIBA should therefore become a
      useful probe in future studies of muscarinic function.

PMID- 1393549
TI  - Enhanced renal response to intracerebroventricular angiotensins II and III in
      spontaneously hypertensive rats.
AB  - The acute effects of intracerebroventricular (i.c.v.) administration of
      angiotensin III (ANG III) on blood pressure (BP) and renal function were
      investigated in spontaneously hypertensive rats (SHR, n = 31) and Wistar-Kyoto
      (WKY) normotensive rats (n = 6). ANG II was also administered to the same rats
      for comparison of its renal effect. BP and renal clearance responses were
      measured before and during ANG injections. The results showed that i.c.v.
      injections of 1, 5 and 50 pmol of ANG III did not significantly alter BP in SHR,
      but a high dose of ANG III (50 pmol) caused a vasopressor effect (7 +/- 4 mmHg)
      in WKY rats. There were significant increases in renal plasma flow (RPF),
      glomerular filtration rate (GFR), urine flow, absolute and fractional excretions
      of sodium and potassium, osmolar clearance and free water reabsorption rate
      following i.c.v. administration of ANG III in both SHR and WKY rats. However, the
      enhancement in renal responsiveness to ANG III was greater in SHR than in the WKY
      group. At 5 pmol of ANG III, the peak increases in GFR (96 +/- 23%), diuresis
      (316 +/- 102%) and natriuresis (712 +/- 281%) in SHR were significantly greater
      than those in WKY rats (40 +/- 13%, 152 +/- 89%, 229 +/- 130%, resp.). The renal
      effect of central ANG III was blocked by i.c.v. ANG III antagonist, [Ile7]-ANG
      III, but was enhanced by bestatin, an ANG III metabolic enzyme inhibitor. I.c.v.
      administration of ANG II at 50 pmol increased BP in both SHR and WKY rats (14 +/-
      3 and 10 +/- 3 mmHg, resp.). Greater diuretic and natriuretic responses to ANG II
      were also noted in SHR than in WKY rats. These results indicate that central ANG
      III is as active as ANG II in modulating renal function. Furthermore, the
      enhanced renal response to i.c.v. ANGs II and III in SHR suggests a hyperactive
      central RAS implicated in BP and body fluid regulation in this genetic
      hypertensive strain.

PMID- 1393550
TI  - Exposure to DDT during a defined period in neonatal life induces permanent
      changes in brain muscarinic receptors and behaviour in adult mice.
AB  - DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] is a potent neurotoxicant in
      both vertebrate and invertebrate species. We have previously reported that
      neonatal exposure to DDT affects the muscarinic cholinergic receptors (MAChR) in
      the cerebral cortex in the neonatal mouse, leading to permanent disturbances in
      the cholinergic system and behaviour of the animals as adults. In order to
      determine if there is a critical period for these effects, mice at the ages of 3
      days, 10-days and 19-days were given a single low oral dose of DDT (0.5 mg/kg
      b.wt.). At adult age (4 months) the mice were tested for spontaneous behaviour:
      'locomotion', 'rearing' and 'total activity', and were subsequently sacrificed
      for measurement of the density of MAChR and subpopulations of MAChR in the
      cerebral cortex by using the muscarinic antagonist quinuclidinyl benzilate,
      [3H]QNB, and agonist carbachol, respectively. A significant increase in
      spontaneous motor behaviour and a significant decrease in MAChR density in the
      cerebral cortex was only observed in adult mice receiving DDT at the age of 10
      days. The induction of these disturbances is limited to peaks in the development
      of spontaneous behavioural activity and MAChR in the neonatal rodent.

PMID- 1393551
TI  - Autoradiographic study of striatal D1 and D2 dopamine receptors in 6-OHDA
      lesioned rats receiving foetal ventral mesencephalic grafts and chronic treatment
      with L-dopa and carbidopa.
AB  - Foetal dopamine cell suspensions or sham preparations were implanted into the
      denervated striatum of rats with a unilateral 6-hydroxy-dopamine (6-OHDA) lesion
      of the medial forebrain bundle. Some animals were also treated with L-DOPA (200
      mg/kg/24 h) and carbidopa (25 mg/kg/24 h) in the drinking water for 5 weeks,
      followed by a 3-week drug-free period. Rotational responses to apomorphine and
      (+)-amphetamine were assessed, and the density of D1 and D2 dopamine receptors
      was evaluated autoradiographically in striatal slices exposed to [3H]SCH 23390 or
      [3H]spiperone. Foetal grafts reduces apomorphine-induced contralateral rotation
      and prevented the development of apomorphine-induced stereotypy. Foetal grafts
      abolished (+)-amphetamine-induced ipsilateral rotation. These effects of the
      grafts were not altered by treatment with L-DOPA. A unilateral 6-OHDA lesion of
      the nigrostriatal pathway resulted in an ipsilateral increase in D2 receptor
      density most marked in the lateral and dorsomedial quadrants of the striatum
      compared with the contralateral side. Foetal ventral mesencephalic grafts
      implanted into the lesioned striatum decreased D2 receptor density to levels
      found in the contralateral intact striatum. Chronic L-DOPA and carbidopa
      treatment did not alter the effect of the grafts. A 6-OHDA lesion resulted in a
      reduction of D1 receptor density in the lateral areas of the lesioned striatum at
      Level 2. The presence of a foetal ventral mesencephalic graft either alone or
      together with L-DOPA treatment did not alter the lesion-induced changes in D1
      binding density.

PMID- 1393552
TI  - Central location of the motoneurons that supply the cucullaris (trapezius) of the
      clearnose skate, Raja eglanteria.
AB  - A complex of three muscles (one lateral, one intermediate and one medial in
      position) in the clearnose skate, Raja eglanteria, is believed to be wholly, or
      in part, homologous to the cucullaris (trapezius). The retrograde transport of
      horseradish peroxidase was used to discover the central location of the
      motoneurons that supply each of these muscles. Motoneurons that project to the
      lateral muscle occupy the caudal part of the ventral nucleus of X. This nucleus
      is situated ventrolateral to the dorsal vagal motor column at caudal medullary
      levels, and lateral to the main ventral motor column of the rostral spinal cord.
      The axons of these motoneurons exit the medulla within the caudal vagal rootlets
      and course peripherally within the intestinal (visceral) ramus of the vagus
      nerve. Motoneurons that innervate the intermediate and medial muscles are located
      along the ventral border of the ventral column of gray at spinal cord segments 10
      15. Their axons course peripherally within the ventral roots of spinal nerves.
      The caudal ventral nucleus of X, the nerve that supplies the lateral muscle, and
      the lateral muscle are likely homologues of the accessory nucleus, accessory
      nerve, and cucullaris (trapezius), respectively, among other fishes and
      tetrapods. Intermediate and medial muscles, based on the central location of
      motoneurons that supply them, are part of the longitudinal epaxial musculature
      and are not part of a trapezius complex.

PMID- 1393553
TI  - Overlap of somatic and visual response areas in the Wulst of pigeon.
AB  - The somatic and visual response areas of the Wulst were investigated
      electrophysiologically in pigeons. Somatosensory neurons are distributed in the
      hyperstriatum accessorium (HA), the hyperstriatum intercalatus superior (HIS) and
      the hyperstraitum dorsal (HD), mainly in HA. The radial nerve response area is
      relatively larger and overlaps the sciatic nerve area. Visual neurons are located
      in HA, especially the more superficial part of HA. In the Wulst, the somatic
      response area overlaps the visual area and there is somatosensory-visual
      convergence.

PMID- 1393554
TI  - Distribution of hypothalamic, medullary and lamina terminalis neurons expressing
      Fos after hemorrhage in conscious rats.
AB  - The immunohistochemical detection of the protein, Fos, has been used as an
      anatomical marker of activated neurons. Three conscious rats were hemorrhaged (4
      ml, 20-25% of blood volume) and the distribution of Fos-stained neurons was
      compared to that in 4 rats which did not have blood removed. In hemorrhaged rats,
      a higher concentration of Fos-stained neurons was present in the lamina
      terminalis, particularly the subfornical organ and organum vasculosum of the
      lamina terminalis, and in the supraoptic and paraventricular nuclei of the
      hypothalamus. In the medulla, Fos-stained neurons were restricted to the nucleus
      of the tractus solitarius, area postrema and the ventrolateral medulla. We
      hypothesize that those neurons are involved in mediating the physiological
      responses to hemorrhage.

PMID- 1393555
TI  - Electric-field-induced reconnection of severed axons.
AB  - We report the first successful axon reconnection in the earthworm (Lumbricus
      terrestris) medial giant axon (MGA) by electric fields generated by electrical
      pulses of 10-100 microseconds duration and 80-200 V amplitude. Reconnection was
      documented by light and electron microscopy, and by transport of Lucifer yellow
      dye across the reconnected MGA segments. Direct repair of a severed nerve axon
      promises the advantages of preserving axon viability and distal connections.

PMID- 1393556
TI  - Differential regulation of manganese and copper/zinc superoxide dismutases by the
      facial nerve transection.
AB  - The effects of unilateral nerve transection on manganese and copper/zinc
      superoxide dismutase (Mn-SOD and Cu/Zn-SOD) mRNA levels in the facial nucleus
      were studied by in situ hybridization. An increase of Mn-SOD mRNA levels was
      first seen in the ipsilateral facial nucleus 12 h after axotomy, and was most
      pronounced at 4-7 days after this procedure; by 56 days, the increase
      disappeared. There was no change in Cu/Zn-SOD mRNA levels at any time after
      axotomy. We further confirmed, by immunohistochemistry, that the increase in Mn
      SOD transcription was followed by protein synthesis. These results are suggestive
      of an important role for Mn-SOD in defense, regeneration and recovery responses
      following nerve transection.

PMID- 1393557
TI  - Potassium-induced depolarization displaces exogenously incorporated gangliosides
      from cortical slices.
AB  - Freshly diced rat cerebral cortical tissue was incubated with [3H]gangliosides
      for 30 min, then perfused for 2 h with different physiological solutions.
      Significantly more labeled (exogenous) gangliosides were displaced when mildly
      depolarizing concentrations (25 mM) of KCl were included in the perfusion medium.
      This provides new evidence for an interaction between gangliosides and membrane
      mechanisms of excitation.

PMID- 1393558
TI  - Phase-resetting effect of 8-OH-DPAT, a serotonin1A receptor agonist, on the
      circadian rhythm of firing rate in the rat suprachiasmatic nuclei in vitro.
AB  - The 5-HTergic neurons in the mesencephalic raphe nuclei provide a robust
      projection to the hypothalamic suprachiasmatic nucleus (SCN), the site of a
      putative neuronal circadian pacemaker. Although it has been suggested that 5-HT
      neurons may play a role in the circadian timing system, this role has not yet
      been specified. Prosser et al. (Brain Res., 534 (1990) 336-339) reported that 1 h
      treatments with quipazine induce robust phase shifts in vitro, and that this
      effect depends upon the circadian time of treatment. However, quipazine is a non
      specific 5-HT agonist. Besides, it is reported that the 5-HT1A agonist, 8-hydroxy
      2-(di-n-propylamino)tetraline hydrobromide (8-OH-DPAT) affected a circadian
      rhythm of hamster wheel-running activity. In the present study we investigated
      whether the 5-HT1A agonist 8-OH-DPAT can reset the phase of the SCN clock when it
      is isolated in vitro. The present results show that 1 h treatments with 8-OH-DPAT
      induce robust phase advances in vitro when it was administered during the
      subjective day. This result suggests that 5HT1A receptor functioning may play a
      role in modulating the phase of SCN clock, especially during the subjective day.

PMID- 1393559
TI  - Effects of advancing age on cerebrospinal fluid concentrations of prolactin in
      the female rat.
AB  - Studies were conducted to determine the effects of advancing age on serum and
      cerebrospinal fluid (CSF) prolactin (PRL) concentrations in the female rat. In
      young rats with basal serum PRL levels, CSF PRL was maintained at 1.1-2.1% of
      serum PRL levels. In middle-aged rats, CSF PRL levels and the ratio of CSF to
      serum PRL was low in rats which maintained estrous cycles, but was increased 4-
      to 10-fold in rats which were in constant estrus. In aged constant estrous rats,
      CSF PRL concentrations were increased markedly and the CSF to serum PRL ratio
      increased to 31%. Collectively, these data indicate that (i) in young female
      rats, only a fraction of serum PRL reaches the CSF; (ii) that CSF PRL
      concentrations are low in middle-aged rats which exhibit estrous cycles and (iii)
      that aging and the constant estrous state are associated with elevated CSF PRL
      concentrations. As such, the age-related elevation in serum PRL levels and the
      fraction of PRL which accumulates in the CSF may contribute to the age-related
      dysfunction in brain PRL-responsive neurons.

PMID- 1393560
TI  - Age-related changes in kynurenic acid production in rat brain.
AB  - Two separate in vitro assays were used to examine the biosynthesis of the broad
      spectrum excitatory amino acid receptor antagonist kynurenic acid (KYNA) during
      the life span of the adult rat. Assessment of KYNA's anabolic enzyme kynurenine
      aminotransferase revealed steady increases between 3 and 24 months of age in all
      five brain regions examined. No changes were observed in the liver. The changes
      were particularly pronounced in the cortex and in the striatum where enzyme
      activity increased three-fold during the period studied. KYNA production from its
      bioprecursor L-kynurenine was also investigated in tissue slices and was found to
      be significantly enhanced in the cortex and hippocampus of old animals. The
      effect of depolarizing agents or sodium replacement was virtually identical in
      tissues from young and old rats. These data, which are in excellent agreement
      with reports on an age-dependent increase of KYNA concentration in brain tissue,
      suggest an enhanced KYNA tone in the aged brain. Together with the reported
      decline in cerebral excitatory amino acid receptor densities with age, increased
      production of KYNA may play a role in cognitive and memory dysfunction in old
      animals.

PMID- 1393561
TI  - Monoaminergic uptake in synaptosomes prepared from frozen brain tissue samples of
      normal and narcoleptic canines.
AB  - Canine narcolepsy, a model of the human disorder, is associated with altered
      catecholamine but not serotonin (5-HT) metabolism in some brain areas,
      particularly the amygdala. A possible explanation for these global changes could
      be the existence of specific defects in monoamine uptake processes. We have
      studied the uptake of [3H]norepinephrine (NE), [3H]dopamine (DA) and [3H]5-HT in
      synaptosomes prepared from cortex and amygdala of narcoleptic and control
      Doberman pinscher brains. Since narcoleptic canines are relatively few in number,
      we have used a specific brain freezing procedure that has been reported to allow
      restoration of metabolically functional tissue upon thawing. Preliminary studies
      comparing monoamine uptake in fresh and frozen brain samples of both groups of
      dogs were carried out and demonstrated that this procedure significantly altered
      serotoninergic but not noradrenergic and dopaminergic uptake. All further
      investigations were then done on synaptosomes prepared from frozen samples. Our
      results demonstrate that synaptosomal uptake of [3H]NE, [3H]DA and [3H]5-HT in
      cortex and amygdala are not altered in narcolepsy.

PMID- 1393562
TI  - A two-trial memory task with automated recording: study in young and aged rats.
AB  - A two-trial recognition task, based on place or object exploration in a Y-maze,
      was developed to study memory in adult and aged rats. This paradigm avoids the
      use of electric shocks or deprivation that may have non-specific influences on
      the responses, and the task does not require learning of a rule. A number of
      behavioral parameters in several animals could be recorded automatically. These
      behavioral parameters were found to be differently influenced both by the type of
      recognition (place vs. object) and by the inter-trial interval (recognition
      retention time). Impaired recognition was also detected in 18-months-old rats.
      This recognition task which combines simplicity, sensitivity and high specificity
      may thus be a useful adjunct to our current battery of memory tasks.

PMID- 1393563
TI  - The oligemic phase of cortical spreading depression is not blocked by tirilazad
      mesylate (U-74006F).
AB  - Cortical spreading depression is characterised by a wave of depolarization that
      moves across the cortex leaving in its wake a state of hyperpolarization.
      Characteristic changes in cerebral blood flow are also seen and these consist of
      a wave of hyperemia followed by an oligemia, the latter lasting some hours in
      some experimental animals including the cat. In this study cerebral blood flow
      was measured using laser Doppler flowmetry in the anesthetised ventilated cat.
      Spreading depression was initiated with a pin-prick injury prior to or following
      administration of U74006F (tirilizad mesylate; 3 mg/kg, ivi) or an identical
      volume of vehicle. Laser Doppler probes were placed bilaterally and in each case
      studied both the hyperemic and oligemic phases of spreading depression were
      preserved after administration of either U74006F or its vehicle. These data
      suggest that free radical mechanisms have no significant role in mediating the
      blood flow changes of spreading depression and are consistent with data in the
      literature of a quantitative using single-point measurements that again U74006F
      does not affect spreading depression.

PMID- 1393564
TI  - Pain-related increases in spinal cord membrane-bound protein kinase C following
      peripheral nerve injury.
AB  - Neuropathic pain following nerve injury is thought to involve central nervous
      system Ca(2+)-mediated neuronal plastic changes. This study provides evidence
      that induction and/or maintenance of post-injury neuropathic pain behaviors in
      the rat is associated with increases in membrane-bound protein kinase C (PKC), a
      Ca(2+)-dependent process known to mediate central nervous system neuronal
      plasticity. In addition, spinal cord administration of GM1 ganglioside, an
      intracellular inhibitor of PKC translocation/activation, reverses both increased
      levels of membrane-bound PKC and pain-related behaviors. Thus, persistent post
      injury neuropathic pain may be mediated by the initiation of excitatory
      neuropathological processes resulting from an increase in membrane-bound PKC.

PMID- 1393565
TI  - Reduction of hibernation bout duration by intraventricular infusion of met
      enkephalin.
AB  - The potential of brain met-enkephalin (met-enk) systems to modulate central
      nervous system (CNS) activity during periods of general depression (modeled by
      the mammalian hibernation state) was studied in the ground squirrel (Citellus
      lateralis). Following entrance into hibernation, continuous met-enk infusion into
      the lateral ventricle (1 microliter/h; 0.2, 1 and 5 micrograms/microliter)
      produced a dose-dependent reduction in bout duration ranging from 1.2 to 3.9 days
      (13.8-44.6% of baseline bout duration). We suggest that the activity of met-enk
      releasing neurons may serve to increase the excitability of the depressed CNS,
      thus accelerating the termination of the hibernation bout.

PMID- 1393566
TI  - Scopolamine attenuates haloperidol-induced c-fos expression in the striatum.
AB  - Haloperidol increases the expression of Fos, the protein product of the proto
      oncogene c-fos, in some parts of the central nervous system. Haloperidol also
      produces catalepsy in rodents and extrapyramidal side effects in humans, both of
      which are reduced by muscarinic receptor antagonists. In order to gain insight
      into the neurochemical and neuroanatomical substrates of haloperidol-induced
      catalepsy we examined the effects of the muscarinic receptor antagonist
      scopolamine on haloperidol-induced Fos expression in the striatum, nucleus
      accumbens and lateral septal nucleus. At a dose that reduced the cataleptic
      effect of haloperidol, scopolamine decreased the neuroleptic-induced Fos
      expression in the striatum and lateral septal nucleus but not the nucleus
      accumbens. These results indicate that haloperidol may increase c-fos expression
      in medium spiny striatal neurons indirectly by enhancing striatal acetylcholine
      release. They are also consistent with the hypothesis that neuroleptic-induced
      increases in striatal c-fos expression are predictive of extrapyramidal side
      effects produced by these compounds.

PMID- 1393567
TI  - Induction of fos expression by activity in the spinal rhythm generator for
      scratching.
AB  - Fos expression was evaluated immunohistochemically in L7-S1 spinal segments after
      inducing fictive scratching in paralysed, unanaesthetized, decerebrate cats. The
      activity was induced by cutaneous stimulation of the pinna on one side and
      recorded from peripheral nerves. A cumulative duration of scratching of 60 to 90
      min was effective in inducing fos expression. Most Fos-positive neurones were
      found in the dorsolateral part of the ventral horn and in the intermediate region
      of the spinal cord on the scratching side. In sham-operated animals the finding
      of Fos-positive neurones in these areas was very rare.

PMID- 1393568
TI  - Differential effects of ibogaine pretreatment on brain levels of morphine and (+)
      amphetamine.
AB  - Previous studies in rats have shown that ibogaine inhibits neurochemical and
      behavioral effects of morphine yet potentiates similar effects of (+)
      amphetamine. To assess whether these different functional interactions have a
      metabolic basis, brain levels of morphine and (+)-amphetamine were measured by
      gas chromatography-mass spectrometry after ibogaine pretreatment (19 h before
      injection of morphine or (+)-amphetamine). Ibogaine pretreatment had no effect on
      brain morphine levels, either at 30 min or 2 h after morphine injection; however,
      ibogaine significantly increased brain amphetamine levels at 30 min and, to a
      greater extent, at 2 h after (+)-amphetamine injection. These and other data
      suggest that ibogaine irreversibly inhibits an amphetamine-metabolizing enzyme.
      The functional interactions between ibogaine and (+)-amphetamine, but not those
      between ibogaine and morphine, may result from a hepatic drug-drug interaction.

PMID- 1393569
TI  - Sick photoreceptors attract activated microglia from the ganglion cell layer: a
      model to study the inflammatory cascades in rats with inherited retinal
      dystrophy.
AB  - Understanding of neuron-glial interactions in neurodegenerative diseases remains
      limited, but is of crucial importance for unravelling the etiology of such
      disorders both in humans and in animals. The present work employed a new,
      function-dependent technique for examining the role of microglia in rats
      afflicted with inherited retinal photoreceptor degeneration (strain: royal
      college of surgeons, RCS). In this rat strain, which served as a surrogate for
      human inherited retinal photoreceptor dystrophy, the optic nerve was cut and the
      ganglion cells were retrogradely labelled with the fluorescent dye 4Di-10ASP. The
      experiment was performed under three different conditions: (1) at the 50th day of
      postnatal age (P50) when there is ongoing degeneration of photoreceptor cells,
      (2) at P110 when most photoreceptors were degenerated and (3) at P50 in non
      dystrophic rats of the Sprague-Dawley strain. After axotomy-induced ganglion cell
      death and labelling of activated microglia by phagocytosis of the ganglion cell
      debris, this study monitored whether the labelled and therefore identifiable
      microglial cells within the severed ganglion cell layer (GCL) are prompted to
      migrate and to participate in phagocytosis of debris produced within the
      endogenously degenerating photoreceptor cell layer (PRL). Massive migration of
      microglial cells from the GCL to the PRL occurred in dystrophic animals with
      optic nerve transection at P50. Double-labelling of microglial cells with the
      fluorescent dye ingested within the GCL and with lipofuscin ingested within the
      PRL indicated the ability of these cells to perform double-phagocytosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1393570
TI  - Expression of c-fos protein by immunohistochemically identified oxytocin neurons
      in the rat hypothalamus upon osmotic stimulation.
AB  - Double immunostaining for c-fos and oxytocin (OXY) was used to study the
      topography and time course of the metabolic activation of the hypothalamic
      oxytocinergic system upon osmotic stress in the male rat. Animals injected i.p.
      with hypertonic saline expressed c-fos-like immunoreactivity (FLI) in the
      paraventricular (PVN), periventricular (PEV) and supraoptic (SON) hypothalamic
      nuclei, and in the preoptic and retrochiasmatic regions, as early as 30 min after
      stimulation and up to 6 h, while these areas were mostly devoid of staining in
      isotonic saline-injected animals. The activation of the oxytocinergic system
      peaked at 30 min and declined at different rates in the PVN and in the SON after
      90 min. The maximal percentage of OXY neurons expressing FLI upon osmotic stress
      was about 80% in the SON, PEV and LSN, 60% in the PVN and 50% in the medial
      preoptic area. Activated OXY neurons were found in both the magnocellular and
      parvocellular divisions of the system. These data show that OXY nuclei in the rat
      hypothalamus are differentially activated by osmotic stress. They also suggest a
      role of OXY in the central as well as in the humoral response to changes in
      plasma osmolarity.

PMID- 1393571
TI  - Electrophysiological actions of acetate, a metabolite of ethanol, on hippocampal
      dentate granule neurons: interactions with adenosine.
AB  - Acetate is the primary breakdown product of ethanol metabolism in the liver and
      has been found in the brain following ethanol ingestion in rats. Systemically
      administered acetate has been shown to cause motor impairment, an effect which is
      blocked by the adenosine receptor blocker, 8-phenyltheophylline (8-PT). The
      effects of sodium acetate were investigated in this study using intracellular
      recording techniques in rat hippocampal dentate granule cells, and were compared
      to the actions of ethanol and adenosine individually and in conjunction with 8
      PT. Acetate hyperpolarized the membrane at 0.4-0.8 mM. The amplitude and duration
      of the postspike train afterhyperpolarization (AHP) were increased by acetate
      when the cell was repolarized to the control resting membrane potential.
      Comparable results were seen in voltage clamp. Acetate also decreased spike
      frequency adaptation. The effects of acetate were mimicked by adenosine (50
      microM) and ethanol (20 mM). The ethanol effects occluded those produced by
      acetate. All of the effects of acetate, adenosine and ethanol could be inhibited
      with prior perfusion of 8-PT (1-10 microM). These data suggest that the actions
      of the major metabolite of ethanol, acetate, may be mediated by adenosine
      receptor activation.

PMID- 1393572
TI  - Arginine vasopressin mobilises intracellular calcium via V1-receptor activation
      in astrocytes (pituicytes) cultured from adult rat neural lobes.
AB  - An extremely close association exists between the membranes of the neurosecretory
      endings and the resident astrocytes (pituicytes) of the neurohypophysis. Indeed,
      synaptoid contacts involving neurosecretory vesicle-containing axons contacting
      pituicytes have been observed, suggesting pituicytes as targets of the products
      released from neurosecretory axons. We have investigated the effects of various
      neural lobe peptides on pituicytes in primary culture from adult neurohypophyses.
      Using Fura-2 loaded cells and dynamic ratio imaging, we have determined that
      arginine vasopressin (AVP) or V1- but not V2-receptor agonists, mobilise
      pituicyte intracellular Ca2+ ([Ca2+]i) in the absence of extracellular Ca2+. AVP
      was consistently effective at concentrations of 10 nM or higher in elevating
      [Ca2+]i by 200-1000 nM. These responses could be blocked by V1-antagonists and
      were shown to be associated with accumulation of phosphoinositides. Oxytocin was
      also found to mobilise [Ca2+]i but was effective only at higher concentrations
      than for AVP. Oxytocin-evoked [Ca2+]i elevations were also blocked by V1
      antagonists. Raising [K+]0 was ineffective in changing [Ca2+]i suggesting that
      these cells lack voltage-gated Ca2+ channels. We conclude that pituicytes possess
      V1-receptors, activation of which mobilises [Ca2+]i, possibly functioning to
      initiate a Ca(2+)-activated K+ conductance which could contribute to further
      depolarisation of secretory terminals and facilitate exocytosis.

PMID- 1393573
TI  - Alterations in behavior, steroid hormones and natural killer cell activity in
      male transgenic TGF alpha mice.
AB  - The expression of transforming growth factor alpha (TGF alpha) is widely
      distributed throughout many normal and neoplastic tissues, but its physiological
      significance remains unclear. We have utilized male transgenic mice
      overexpressing the gene encoding human TGF alpha in multiple tissues to further
      identify those functions which are influenced by this protein. Male TGF alpha
      mice develop hepatocellular carcinoma at the age of 10-15 months. At the age of 2
      3 months these mice, compared to age matched CD-1 controls, spent significantly
      longer times immobile in Porsolt's swim test, a model of stress and depressive
      behavior, and exhibiting aggressive behavior in the resident-intruder test. In
      contrast, the transgenic TGF alpha mice did not differ from the controls in
      either the plusmaze test of anxiety, or in their voluntary alcohol intake.
      Significantly, the TGF alpha mice exhibited a 25% lower Natural Killer (NK) cell
      activity and a four-fold increase in the plasma levels of 17-beta-estradiol (E2)
      than the controls. No significant changes in plasma testosterone or
      corticosterone levels were noted. The results indicate that transgenic male mice
      overexpressing TGF alpha exhibit behaviors characteristic of both an impaired
      ability to cope with stress and an increased aggressivity. The TGF alpha mice
      also show reduced NK cell activity and increased plasma estradiol concentrations.
      The present data suggest that TGF alpha may be important in influencing
      behavioral, immunological and hormonal systems prior to the onset of tumors. It
      remains to be determined whether hepatocarcinoma is associated with the direct
      proliferative and transforming effects of TGF alpha and/or indirect effects
      mediated through immune, hormonal and behavioral mechanisms.

PMID- 1393574
TI  - Electrical stimulation of the paraventricular nucleus attenuates pyrogen fever in
      the rabbit.
AB  - Arginine vasopressin (AVP) perfused within the ventral septal area (VSA)
      suppresses fever normally evoked by pyrogenic substances, including Salmonella
      abortus equi (SAE). Neurons containing AVP and located within the paraventricular
      nucleus (PVN) or the nearby bed nucleus of the stria terminalis (BnST) are
      believed to have projections to this septal region. A series of experiments was
      undertaken to determine whether electrical stimulation of these areas, which
      might be expected to cause the release of AVP within the VSA, would affect
      similarly the pathogenesis of fever. A stainless steel cannula was implanted
      surgically in each of 22 male New Zealand White rabbits and a monopolar electrode
      was lowered through this guide cannula to the PVN or BnST areas. Electrical
      stimulation (20 Hz, 10 s on, 10 s off, 2.6-3.2 V) was initiated 30 min prior to
      and was continued until 90 min after the intravenous (i.v.) administration of 0.1
      1.0 micrograms of SAE (1.0 ml carrier vehicle). While afebrile body temperature
      remained unchanged, electrical stimulation of sites located in the rostral
      extension of the PVN effectively attenuated the pyrogen-induced fever.
      Stimulation of sites outside these areas did not affect either the absolute
      magnitude or the duration of the fever. Although the reduction in fever was most
      pronounced during the period of electrical stimulation, in some cases the fever
      remained suppressed beyond the application of the current. These experiments
      provide the first evidence that electrical stimulation of paraventricular areas
      with AVP-containing cell bodies is effective in suppressing a fever evoked by
      systemic administration of a pyrogen. Although untested, it is possible that a
      stimulus-induced release of AVP within the VSA is responsible for the attenuation
      of the fever.

PMID- 1393575
TI  - Angiotensinogen is secreted by pure rat neuronal cell cultures.
AB  - Previous studies are divided between those which support a neuroglial (astrocyte)
      source for brain angiotensinogen and those which indicate that both astrocytes
      and neurones synthesize the precursor of angiotensin II. In this study, separate
      cultures of astrocytes and neuronal cells were prepared and established as being
      essentially pure by appropriate immunocytochemical cell markers. Angiotensinogen
      production by these cultures, as measured by a direct radioimmunoassay, was 20.74
      +/- 3.62 ng angiotensinogen/10(6) cells/24 h (mean +/- S.D., n = 8) for
      astrocytes and 4.39 +/- 0.94 ng/10(6) cells/24 h (mean +/- S.D., n = 29) for
      neurones. Angiotensinogen secretion from both cell types was unaffected by
      treatments which stimulate the regulatory secretory pathway by modulating
      intracellular cAMP levels. In contrast, it was reduced from 23.20 +/- 2.14 to
      8.14 +/- 1.31 ng/10(6) cells/24 h (S.E.M., n = 7) in astrocyte cultures by the
      constitutive pathway inhibitor, monensin. Angiotensinogen secreted by astrocytes
      and neurones was compared to pure angiotensinogen and that in plasma and
      cerebrospinal fluid (CSF) by cation-exchange mono S column chromatography. Pure
      angiotensinogen eluted as two separate peaks corresponding to the major forms of
      plasma angiotensinogen, whereas angiotensinogen in CSF and culture media coeluted
      with a third minor form of plasma angiotensinogen. It was concluded that neuronal
      cells as well as astrocytes secrete angiotensinogen which is distinctly different
      from plasma angiotensinogen.

PMID- 1393577
TI  - Effects of 5-HT receptor antagonists on seizure susceptibility and locomotor
      activity in DBA/2 mice.
AB  - The effect of antagonists of serotonin (5-HT) receptor subtypes and alpha 2
      adrenoceptors was investigated on audiogenic seizures and locomotor activity in
      DBA/2 mice. 5HT1c receptor antagonists (mianserin and cyproheptadine), 5-HT3
      receptor antagonist (zacopride) and 5-HT4 receptor antagonist (ICS 205-930)
      increased the latency of audiogenic seizures and decreased the severity of
      convulsions in young (20-27 days old) DBA/2 mice. However, the effect of these
      antagonists varied in older (30-37 days old) mice. Ketanserin, 5-HT2 receptor
      antagonist, was devoid of any activity on audiogenic seizures. Yohimbine (0.5
      mg/kg, i.p.), an alpha 2-adrenoceptor antagonist, increased the severity of
      audiogenic seizures, and the anti-convulsant effect of 5-HT receptor subtypes
      antagonists became more pronounced in the presence of yohimbine. 5-HT3 and 5-HT4
      receptor antagonists produced hypolocomotor activity in young mice whereas 5-HT1c
      and 5-HT2 receptor antagonists were devoid of any effect on locomotor activity.
      Yohimbine did not induce any effect on locomotor activity but the mice exhibited
      more pronounced hypolocomotor activity following the administration of 5-HT3, 5
      HT4 and 5HT1c receptor antagonists in the presence of yohimbine. However, the
      results varied with these agents in the older mice. These observations implicate
      a role of 5-HT1c, 5-HT3, 5-HT4 and alpha 2-adrenoceptors in audiogenic seizures
      in young DBA/2 mice, and 5-HT3 and 5-HT4 receptors in locomotor activity in these
      mice. Furthermore, these results also suggest an interaction between 5-HT
      receptors and alpha 2-adrenoceptors, and differential development patterns of
      various 5-HT receptor subtypes in the CNS.

PMID- 1393576
TI  - Antagonism of cocaine's pharmacological effects by the stimulant dopaminergic
      antagonists, (+)-AJ76 and (+)-UH232.
AB  - The aminotetralins (+)-AJ76 and (+)-UH232 are stimulant dopaminergic antagonists,
      which may preferentially antagonize autoreceptors of dopamine nerve terminals.
      Both agents antagonized cocaine's depressant effects on firing rates of ventral
      tegmental dopaminergic neurons, but (+)-UH232 was much more potent. When injected
      simultaneously with cocaine, (+)-UH232 inhibited and (+)-AJ76 enhanced the
      locomotor stimulation observed during the first 30 min following s.c. cocaine
      administration. However, (+)-AJ76 antagonized cocaine-induced stereotypies as
      well as the later more intense cocaine locomotor stimulation. It is suggested
      that preferential dopamine autoreceptor antagonists may provide a novel approach
      to a pharmacotherapy for treating cocaine abuse.

PMID- 1393578
TI  - Ceruletide, a CCK-like peptide, attenuates dopamine release from the rat striatum
      via a central site of action.
AB  - Ceruletide (CLT), a cholecystokinin-like peptide was given subcutaneously or via
      the perfusate to rats to clarify the site of action (peripheral vs. central
      location) of CLT, using in vivo microdialysis techniques. Striatal dopamine (DA)
      release induced by haloperidol (HPD) was significantly inhibited by
      subcutaneously administered CLT (160 micrograms/kg) when given with a perfusate
      containing 15 mM K+. Subdiaphragmatic vagotomies failed to block the inhibitory
      effect of CLT. CLT (10(-15)-10(-11) M) locally applied, via a dialysis tube,
      produced an inhibitory effect on HPD-induced DA release in the striatum in a dose
      dependent manner. The inhibitory effect of CLT given subcutaneously on DA release
      was antagonized by both locally applied proglumide and systemically administered
      L-365,260. These findings suggest that systemically administered CLT can directly
      act on the striatal neurons via CCK-B receptors and produce an inhibitory effect
      on DA release in the striatum under appropriate depolarization.

PMID- 1393579
TI  - [3H]MK-801 binding to the NMDA receptor complex, and its modulation in human
      frontal cortex during development and aging.
AB  - [3H]MK-801 binding was found to decline with age in well washed membranes from
      human frontal cortex taken from an age series from 24 weeks gestation to 100
      years old. The decline was significant under basal conditions (no added
      modulators) (P less than 0.01), and highly significant under stimulation with
      glutamate, glycine and spermidine alone and in combination (P less than 0.001).
      Scatchard analysis in the presence of glutamate and glycine showed this decline
      was due to a loss in the number of [3H]MK-801 binding sites rather than a change
      in the affinity of the binding site. There was a highly significant age related
      reduction in the attenuation of [3H]MK-801 binding by zinc (P less than 0.001).
      In foetal and neonatal cases up to 7 weeks of age spermidine behaved in an
      antagonistic manner, inhibiting rather than stimulating [3H]MK-801 binding, when
      alone or in the presence of glutamate and glycine. The changes in influence of
      glutamate, glycine, spermidine and zinc on [3H]MK-801 binding during development
      and aging were not due to other pre- or postmortem factors. The reverse effect of
      spermidine in the foetal and neonatal cases has therapeutic implications in the
      treatment of neonates with antiischaemic agents whose action involves the
      polyamine site.

PMID- 1393580
TI  - Regional distribution of copper, zinc and iron in the brain in Long-Evans
      Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis.
AB  - In Long-Evans Cinnamon (LEC) rats of three different ages (7, 13 and 32 weeks
      old) concentrations of Cu, Zn and Fe were measured in 8 regions of the brain. The
      LEC groups aged 7 and 13 weeks showed low concentrations of Cu in all regions
      compared to Long-Evans Agouti (LEA) rats. In 32-week-old LEC rats, however, Cu
      concentrations increased in 7 regions, in particular, significantly so in the
      striatum, hypothalamus, cerebellum, midbrain and cortex. Changes of Zn
      concentration were not found in any region. The Fe concentration increased in
      cortex and olfactory lobes. The three LEC groups showed a very high concentration
      of hepatic Cu and a low concentration of serum Cu compared to LEA rats. In LEC
      rats aged 32 weeks, however, hepatic Cu decreased and serum Cu increased compared
      to the other two LEC groups. These results suggest that the increase of the
      cerebral Cu concentration is closely related to the inherently abnormal Cu
      metabolism and then to the changes of Cu metabolism from about 13 weeks after
      birth.

PMID- 1393581
TI  - Appearance of interleukin-1 in macrophages and in ramified microglia in the brain
      of endotoxin-treated rats: a pathway for the induction of non-specific symptoms
      of sickness?
AB  - The presence and cellular localization of interleukin-1 beta immunoreactivity
      (irIL-1) in and around the brain was investigated using immunocytochemistry on
      Bouin's fixed vibratome brain sections of control and endotoxin-treated rats.
      Peripheral administration of endotoxin resulted in the appearance of irIL-1 in
      cells in the meninges, choroid plexus, brain blood vessels and in non-neuronal
      cells in the brain parenchyma. Using monoclonal and polyclonal antibodies to
      macrophage and astrocyte antigens, the endotoxin-induced irIL-1 positive cells
      could be identified as macrophages in the meninges and choroid plexus (ED2),
      perivascular cells (ED2) and ramified microglial cells (GSA-I-B4 isolectin). Our
      data demonstrate a pathway for the induction of non-specific sickness symptoms in
      response to endotoxin.

PMID- 1393582
TI  - Capillary NMDA receptors regulate blood-brain barrier function and breakdown.
AB  - Polyamines and their regulatory synthetic enzyme ornithine decarboxylase (ODC)
      have been implicated in blood-brain barrier (BBB) breakdown following cryogenic
      injury. ODC activation and BBB breakdown are prevented by MK-801, indicating
      involvement of NMDA receptors. Studies in isolated rat cerebral capillaries
      supports the presence of NMDA receptors linked to ODC. NMDA (1-50 microM)
      stimulated capillary uptake of horseradish peroxidase, 2-deoxy-[14C]glucose, and
      45 Ca in a receptor-, concentration-, polyamine- and Ca(2+)-dependent manner. We
      suggest that NMDA receptors may couple capillary transport of nutrients to
      glutamate-mediated neuronal excitation, and when overestimated disrupt normal BBB
      function.

PMID- 1393583
TI  - Sexually dimorphic concentrations of arginine vasotocin in sensory regions of the
      amphibian brain.
AB  - Arginine vasotocin (AVT) regulates reproductive behaviors in amphibians. We
      measured AVT in the brains of bullfrogs (Rana catesbeiana) and newts (Taricha
      granulosa) using radioimmunoassay. In bullfrogs, AVT concentrations were greater
      in males, compared to females, in the amygdala pars lateralis, optic tectum, and
      tegmentum. Concentrations in the dorsolateral nucleus were greater in females. In
      newts, AVT concentrations were also greater in the tectum and tegmentum of males.
      AVT may modulate dimorphic behaviors by acting at these sites.

PMID- 1393584
TI  - The morphology of GABA-immunoreactive neurons in the accessory olfactory bulb of
      rats.
AB  - GABA-immunoreactive (IR) neurons were observed in the accessory olfactory bulb
      (AOB) of adult female rats. Many somata and dendritic trees of periglomerular
      located cells were GABA-IR and the size of their somata was variable. Numerous
      somata and dendrites in the granule cell layer were IR. These results suggest
      that a large number of the interneurons in the AOB are GABA-IR.

PMID- 1393585
TI  - Effect of angiotensin II and atrial natriuretic factor on neurons in the
      subfornical organ of ducks and rats in vitro.
AB  - Atrial natriuretic factor (ANF) antagonizes many angiotensin II (ANGII)-induced
      effects on osmoregulatory relevant parameters in vivo. In this study ANF
      analogues decreased the spontaneous and the ANGII-induced electrical activity of
      subfornical organ (SFO) neurons in rats, but had no effect on ANGII sensitive or
      insensitive SFO neurons in ducks. These results suggest a more distinct
      functional separation for the responsiveness to ANGII and ANF in birds compared
      to mammals.

PMID- 1393586
TI  - In vivo kindling does not alter afterhyperpolarizations (AHPs) following action
      potential firing in vitro in basolateral amygdala neurons.
AB  - Kindling in vivo results in enhanced glutamatergic synaptic transmission and
      epileptiform bursting in vitro in neurons of the basolateral amygdala (BLA). We
      tested the hypothesis that reduction of intrinsic inhibitory mechanisms, such as
      the slow- and medium-afterhyperpolarizations (s-AHPs, m-AHPs), contributes to the
      enhanced neuronal excitability observed in kindling-induced epileptogenesis using
      intracellular recording methodology. In these studies, neurons were recorded from
      the BLA contralateral to the kindling site. AHPs following depolarizing current
      induced (100 ms, 1 nA) action potentials were recorded from BLA neurons of
      control and kindled animals. We found no difference in the amplitude of the s-AHP
      and m-AHP, or the duration of the s-AHP between control and kindled neurons. In
      addition, kindling did not alter the distribution of accommodating/non
      accommodating BLA neurons (as assessed from neuronal responses during long (500
      ms) depolarizing current injection). It is concluded that an alteration in the
      neuronal network within the BLA rather than a blockade of an intrinsic inhibitory
      mechanism underlies the enhanced excitability recorded in BLA neurons following
      kindling.

PMID- 1393587
TI  - Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons.
AB  - The hippocampus is vulnerable to the damaging actions of insults such as
      transient ischemia and repetitive stimulation, as well as repeated exposure to
      exogenous glucocorticoids. This study investigated effects of a repeated
      psychological stressor, restraint, on the CA3 pyramidal neurons which are
      vulnerable to damage by repetitive stimulation. Repeated daily restraint stress
      for 21 days caused apical dendrites of CA3 pyramidal neurons to atrophy, while
      basal CA3 dendrites did not change. Rats undergoing this treatment were healthy
      and showed some adaptation of the glucocorticoid stress response over 21 days;
      however, stress reduced body weight gain by 14% and increased adrenal weight
      relative to body weight by 20%. Results are discussed in relation to the possible
      role of adrenal steroids and excitatory amino acids.

PMID- 1393588
TI  - The effect of cycloheximide on natural and X-ray-induced cell death in the
      developing cerebral cortex.
AB  - Naturally occurring cell death in the cerebral cortex and subcortical white
      matter is increased after X-irradiation, and this process is curbed with
      cycloheximide, an inhibitor of protein synthesis. However, cycloheximide alone
      increases cell death during development, and this effect is dose-dependent. This
      suggests that, in both normal and experimentally-induced cortical cell death
      during development, different proteins are activated or inhibited, depending on
      the agent, the time of its application, and the previous metabolic or functional
      state of the cell.

PMID- 1393589
TI  - Brain implants in man do not break down the blood-brain barrier to dopamine and
      domperidone.
AB  - We have evaluated the blood-brain barrier (BBB) in 8 Parkinsonian patients before
      and after stereotactic implantation of foetal mesencephalon (STIM) and one
      patient with an adrenal medullary implant. Parenteral administration of dopamine
      did not reverse Parkinsonism pre-operatively or at 5 days, 1, 2, 3, 4 months and
      1 year post-operatively. Apomorphine and domperidone reversed Parkinsonism and
      produced dyskinesia in all patients pre- and post-operatively. We conclude that
      the BBB remains intact to dopamine following implantation.

PMID- 1393591
TI  - A topographic representation of auditory space in the external nucleus of the
      inferior colliculus of the guinea-pig.
AB  - The possibility that the external nucleus of the inferior colliculus (ICX) of the
      pigmented guinea-pig contains a map of auditory space has been investigated.
      Auditory stimuli consisted of broad-band sound delivered under free-field
      anechoic conditions from a range of positions around the animal's azimuthal axis.
      The responses of clusters of neurons in the ICX to threshold and to near
      threshold stimuli displayed sharp spatial tuning. The responses recorded from
      rostral ICX revealed a preference for auditory stimuli in the anterior field
      while more caudal neurons preferentially responded to sounds presented in the
      posterior field. Neurons at intermediate points, along the rostro-caudal axis of
      the nucleus, displayed preferences for sound stimuli in appropriately
      intermediate field positions along the contralateral azimuthal axis. At higher
      stimulus intensities the spatial tuning of the responses decreased, but the
      optimal direction of preference was usually retained. The contribution of
      binaural processing to auditory spatial tuning was evident, since unilateral
      cochlea ablation destroyed the spatial tuning at higher stimulus intensities. The
      results presented provide the first evidence that a topographically ordered
      representation of the contralateral auditory azimuth is present in the ICX of a
      mammal.

PMID- 1393590
TI  - A calcium-stimulated serine protease from monkey brain degrades the beta-amyloid
      precursor protein.
AB  - Amyloid deposition, a histopathological feature of Alzheimer's disease brain, may
      be the underlying cause of this disease. The isolation of enzymes involved in
      both the normal and aberrant or alternative processing of the beta-amyloid
      precursor protein may lead to an understanding of how beta-protein, the major
      component of amyloid deposits, is formed in the brain parenchyma and vasculature
      of Alzheimer's disease patients and aged humans. As the same kind of deposits is
      also found in aged primates, the use of primates will undoubtedly help to
      understand the mechanisms of amyloid deposition, both spatially and temporally.
      Here we report the partial purification from adult monkey brain of a calcium
      activated serine protease that is immunoreactive with antibodies against
      cathepsin G and is potentially involved in the abnormal degradation of the beta
      amyloid precursor protein. Moreover, immunoreactivity with cathepsin G antibodies
      was localised to astrocytes in both adult and aged monkey cortex, suggesting that
      our protease may be expressed in astrocytes.

PMID- 1393592
TI  - Effect of orbital enucleation on glucose homeostasis and morphology of the
      suprachiasmatic nucleus.
AB  - In rats there is a direct neural connection called the retinohypothalamic tract
      (RHT) from retinal ganglion cells to the ventrolateral part of the
      suprachiasmatic nucleus (SCN), which has neurons containing vasoactive intestinal
      polypeptide (VIP)-like substance. Previously, we observed that bilateral orbital
      enucleation (blinding) caused temporary suppression of the hyperglycemic response
      to intracranial injection of 2-deoxy-D-glucose (2DG) from week 4 to 6 after
      blinding. Moreover, bilateral lesions of the SCN had a similar effect. From these
      findings, we supposed that the neurons responsible for the hyperglycemic response
      to 2DG were present in the SCN, that after blinding these neurons temporarily
      lost their activity, and that this functional change was reflected in the
      morphology of the SCN. To investigate this possibility, we examined the
      morphological changes of the SCN by Nissl staining and immunohistochemical
      studies with anti-VIP and anti-peptide histidine isoleucine (PHI) antibodies in
      blinded rats, and the relationship between these morphological changes and the
      hyperglycemic response to 2DG. After surgical blinding, we observed following
      changes. (1) The optic chiasm became thinner. (2) The SCN became displaced
      rostrally. (3) The density of neurons in the middle to caudal part of the SCN,
      where the retinal ganglion cells projected, decreased markedly without change in
      cell number during the period when the hyperglycemic response to intracranial
      injection of 2DG was temporarily suppressed after blinding. The first and second
      changes seemed to reflect reduction of fibers and axon terminals of retinal
      ganglion cells and their innervation, respectively. As the third change was
      parallel with suppression of the hyperglycemic response to 2DG injection, it may
      reflect functional change of the neurons in the SCN that are responsible for the
      hyperglycemia due to 2DG.

PMID- 1393593
TI  - Sleep homeostasis in suprachiasmatic nuclei-lesioned rats: effects of sleep
      deprivation and triazolam administration.
AB  - The electroencephalogram (EEG) and electromyogram of rats with lesions in the
      suprachiasmatic nuclei (SCNx) were recorded during two series of 24-h baseline, 6
      h sleep deprivation (SD), and 24-h recovery. At recovery onset, rats were
      injected i.p. with vehicle (VEH) control solution or 0.4 mg/kg triazolam (TRZ) in
      a balanced crossover design. Consecutive 10-s epochs were scored for vigilance
      states and EEG power spectra were computed. Arousal states were uniformly
      distributed during 24-h baseline (wake 47% of recording time, non-rapid-eye
      movement sleep (nonREMS) 47%, REMS 7%), and EEG spectra (0-25 Hz) were devoid of
      significant trends. State-specific EEG power spectra profiles in SCNx rats were
      similar to those of intact animals reported previously. However, EEG delta power
      (0.5-3.5 Hz) of nonREMS was markedly lower in SCNx rats. Recovery from 6-h SD was
      characterised by a short-lasting reduction of REMS, and a long-lasting increase
      of nonREMS time at the cost of wakefulness. EEG delta power rebounded during the
      first 8 h in recovery, and fell below baseline level after 12 h in recovery.
      During 0-2 h TRZ recovery, rats spent more time in nonREMS with higher EEG slow
      wave activity as compared to the corresponding VEH recovery period. EEG slow wave
      activity fell below baseline levels 10 h after TRZ injection and termination of
      SD. We conclude that major features of homeostatic sleep EEG regulation are
      present in SCNx rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393594
TI  - Early post-natal administration of 5,7-dihydroxytryptamine destroys 5-HT neurons
      but does not affect spatial memory.
AB  - The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) may play an important
      role in learning and memory. It has also been suggested that 5-HT abnormalities
      may mediate some aspects of the cognitive disorders associated with Korsakoff
      syndrome and Alzheimer's Disease. The effect of intracisternally applied 5-HT
      neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) on learning and memory in rodents
      was evaluated. Three-day-old rat pups were treated with pargyline (40 mg/kg,
      i.p.) followed by 5,7-DHT (50 micrograms/pup) and returned to the dam for a
      month. At 75 days of age, rats were tested on a learning set problem in the
      Morris water maze for 5 days followed by 30 days of testing in a 12-arm radial
      maze with 8 of the 12 arms baited. In the Morris water maze, the latency to
      locate the hidden platform did not differ significantly for 5,7-DHT treated and
      control rats (F less than 1.0). Similarly, 5,7-DHT treated rats performed
      comparably to controls on the 12-arm radial maze (F less than 1.0). At 106 days
      of age the assay of tryptophan hydroxylase activity in the dorsal raphe nuclei
      and hippocampus showed marked reduction (86%, 78%, respectively) in 5,7-DHT
      treated animals compared to vehicle injected controls. Immunocytochemical
      analysis was consistent with the biochemical results. In 5,7-DHT treated animals
      there was severe loss of neurons that bind 5-HT antibody in the dorsal and medial
      raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393595
TI  - Role of the cell recognition molecule, cognin, in GABAergic differentiation in
      chick retina.
AB  - Previous work showed that GABAergic differentiation in developing chick retina
      depends on insulin and cell interactions. Here, we investigated whether it
      depended on cell signaling mediated by retina cognin, a 50 kDa cell recognition
      molecule. Cognin mediates cell adhesion in vitro and occurs on retinal neurons
      that become both GABAergic and cholinergic. We investigated two markers of
      GABAergic differentiation: glutamate decarboxylase (GAD) activity and high
      affinity GABA uptake. Both increase during differentiation of retinal neurons in
      culture and can be easily measured. We blocked cognin-mediated cell signaling
      with cognin antibody and found a reduction of the developmental increase in GAD
      activity in cultures of retinal neurons from 7 and 11 day chick embryos. There
      was no reduction of high-affinity GABA uptake. This suggested that cognin
      mediated signaling was necessary for the normal developmental increase in GAD but
      not for high-affinity GABA uptake. These results contrasted with our previous
      observations on cholinergic differentiation in cultured retinal neurons. We found
      that cognin antibody blocked the normal developmental increase in choline
      acetyltransferase (ChAT) only if the cells were exposed before embryonic day 7.
      Thus, while both GAD and ChAT activity appear to be controlled by cell signaling
      involving cognin, the periods of developmental sensitivity for the two
      differentiation markers are different. Antibodies to other adhesion molecules, Ng
      CAM, and N-cadherin, did not similarly affect GAD activity. Antibodies to laminin
      at a 10-fold higher concentration inhibited GAD activity only in early embryonic
      retina. Tests for protein synthesis and "housekeeping" enzyme activity
      demonstrated that the cognin antibody effect was selective for neuronal
      differentiation pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393596
TI  - Interregional correlations of resting cerebral glucose metabolism in old and
      young women.
AB  - A correlational analysis of normalized (regional to whole-brain) regional
      cerebral metabolic rates for glucose obtained in the 'resting' state (eyes
      covered, ears plugged) using [18F]fluorodeoxyglucose, demonstrated differences
      between old and young women in patterns of functional associations. Fifteen
      healthy young (age less than 40 years) and 17 healthy old women (age greater than
      64 years) were scanned with a Scanditronix PC1024-7B tomograph. The brain was
      divided into 65 regions of interest. The old women had fewer and less positive
      correlations between pairs of metabolic ratios in the frontal and parietal
      cortices. The results suggest an age-related reduction in frontal and parietal
      functional interactions in the 'resting' state that is consistent with a prior
      correlation analysis using a low resolution ECAT II scanner on young and old men.
      Reduced functional interactions may reflect age-related cognitive changes.

PMID- 1393597
TI  - Differential inhibition of acetylcholinesterase molecular forms in normal and
      Alzheimer disease brain.
AB  - Molecular forms of acetylcholinesterase were studied in three brain regions from
      Alzheimer disease patients and non-demented, age-matched controls. In Alzheimer
      disease patients, the membrane-bound G4 form was decreased in frontal (-71%) and
      parietal cortex (-45%) and in the caudate-putamen (-47%) from control levels. We
      also found a decrease of aqueous-soluble acetylcholinesterase molecular forms in
      the aqueous-soluble acetylcholinesterase molecular forms in the caudate-putamen
      region. The effect of three clinically significant acetylcholinesterase
      inhibitors, heptyl-physostigmine, physostigmine and edrophonium, on aqueous
      soluble acetylcholinesterase molecular forms of the caudate-putamen was
      investigated. Heptyl-physostigmine, a physostigmine analogue, showed preferential
      inhibition for the G1 form. On the contrary, edrophonium inhibited the G4 form
      more potently than the G1 form. Physostigmine inhibited both forms with similar
      potency. The clinical implications of selective acetylcholinesterase inhibitors
      are discussed.

PMID- 1393598
TI  - Aromatase activity in cultured brain cells: difference between neurons and glia.
AB  - At the level of the central nervous system (CNS) of several mammalian and non
      mammalian species, estrogens may be intracellularly formed from circulating
      androgens through the action of the aromatase complex. Estrogenic steroids play a
      crucial role in organizing and directing certain behavioral and neuroendocrine
      responses both during the fetal/neonatal life and in adulthood. Biochemical and
      immunocytochemical studies have shown that the aromatase is particularly
      concentrated in CNS areas involved in the control of reproductive functions, such
      as the hypothalamus, the preoptic area and the limbic system; despite this large
      body of evidence, the exact cellular localization of this enzymatic complex
      within the different cell populations of the brain is still uncertain. In the
      experiments described here, the presence of the aromatase has been evaluated in
      the two main cellular components of the brain: the neurons and the glia. In these
      experiments, cultures of neurons obtained from the brains of 14-15-day-old rat
      embryos, mixed glial cells from 1-day-old rats and type 1 astrocytes derived from
      cultured glial cells, have been utilized. The aromatase has been also evaluated
      in oligodendrocytes isolated from adult male rat brain by density gradient
      ultracentrifugation. The aromatase activity has been assayed by an 'in vitro'
      radiometric method which quantifies the production of tritiated water from [1
      beta-3H]-androstenedione as an index of estrogen formation. The validity of the
      method has been verified both on the placental microsomes and on rat hypothalamic
      tissue, in which the actual formation of estrogens has also been
      measured.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393599
TI  - Basal forebrain cholinergic neurons in aged rat brain are more susceptible to
      ibotenate-induced degeneration than neurons in young adult brain.
AB  - Choline acetyltransferase (ChAT) activity, acetylcholinesterase (AChE) activity,
      and [3H]nicotine binding site density were measured in neocortex from unoperated
      (control) and nucleus basalis (NB)-lesioned young (2-3 months old) and aged (23
      24 months old) rats. In control animals, neither enzyme activities nor the
      density of nicotine binding sites were altered as a function of age. However, age
      related differences were apparent 2 weeks following unilateral infusions of
      ibotenic acid into the right NB. NB lesion-induced decreases in enzyme activities
      were significantly greater in ipsilateral neocortices from aged rats; ChAT and
      AChE activities in young animals decreased by 59 and 53%, respectively, while
      both enzyme activities in aged rats decreased by 72%. NB lesions decreased
      significantly the density of nicotine binding sites in ipsilateral neocortices
      from both young and aged rats; binding decreased by 23-26% in young rats and by
      31-34% in aged animals. Results indicate that the basal forebrain cholinergic
      system in the aged rat is more susceptible to ibotenate-induced degeneration than
      neurons in young animals.

PMID- 1393600
TI  - Enhancement of REM sleep with auditory stimulation in young and old rats.
AB  - Auditory stimulation applied during rapid eye movement (REM) sleep enhances the
      duration of REM sleep in cats and humans. The present experiment investigated
      whether auditory stimulation would enhance REM sleep in young (3-6 months) rats,
      and also in old (22-24 months) rats which have impaired REM sleep. Baseline sleep
      records were obtained on two days. Sleep patterns were then assessed during
      auditory stimulation test sessions. In young rats, auditory stimulation was
      administered during each REM sleep bout. In old rats, auditory stimulation was
      administered on a fixed schedule (10 min of stimulation alternating with 15 min
      quiet). The day after the stimulation session, an additional sleep record (Day 2)
      was obtained for each rat. In young rats, auditory stimulation enhanced both REM
      sleep duration and total REM sleep time. In the old rats, which showed impaired
      sleep measures as compared to young animals, auditory stimulation enhanced both
      total REM sleep time and the number of REM sleep periods. Residual proactive
      effects of auditory stimulation (Day 2) were observed in both young and old rats.
      Thus, auditory stimulation is an effective manipulation with which to augment REM
      sleep in both young and old rats, and partially attenuates REM sleep impairments
      in old rats.

PMID- 1393601
TI  - The evidence for astrocytes as a target for central noradrenergic activity:
      expression of adrenergic receptors.
AB  - Our recognition and understanding of adrenergic receptor expression by astrocytes
      and their cultured counterparts, astroglia, has occurred primarily over the past
      2 decades. The advances in our knowledge have come about largely through the
      advent of new techniques with which to study neurotransmitter receptors, coupled
      with improvements in our ability to isolate, purify, and identify this central
      nervous system (CNS) cell type. The development of pharmacological tools such as
      second messenger assays, iodinated ligands, autoradiography, and intracellular
      electrophysiological recordings, paralleled that of cultured clonal cells lines
      of glial origin, purified astroglial primary cultures, isolations of astrocytes
      from adult tissues, and immunocytochemical staining for the astrocyte-specific
      glial fibrillary acidic protein (GFAP). As these techniques were combined and
      applied to the study of astrocyte pharmacology, our understanding of adrenergic
      receptor expression by these cells deepened. This review is an account of how
      these events have shaped our understanding of astrocytic adrenergic receptor
      expression.

PMID- 1393602
TI  - Resting and reactive astrocytes express adrenergic receptors in the adult rat
      brain.
AB  - Adrenergic receptor subtypes were localized in situ and in cells isolated from
      the trigeminal motor nucleus and several other brain regions. To study receptor
      expression in reactive astrocytes, motor neuron degeneration and a glial reaction
      were induced in the trigeminal motor nucleus by the injection of the toxic lectin
      Ricin communis into the trigeminal motor root. Autoradiography following
      incubation of tissue sections in the alpha 1-ligand 125IBE 2254 (HEAT) or the
      beta-ligand 125Iodocyanopindolol (ICYP) showed a decrease in alpha 1- and an
      increase in beta-adrenergic receptor binding in the region of neuronal
      degeneration and gliosis. Glial hypertrophy, rather than hyperplasia, appears to
      be mainly responsible for the increased beta-binding, since inhibition of mitosis
      with cytosine arabinofuranoside only partially blocked elevations of beta
      adrenergic receptor binding and GFAP immunolabelling in reactive astrocytes. More
      direct evidence for the expression of adrenergic receptors in normal and reactive
      astrocytes was obtained by combined autoradiography and immunohistochemistry of
      cells dissociated from the cerebral cortex, striatum, cerebellum, and trigeminal
      motor nucleus of adult rats. More than 88% of GFAP-positive astrocytes showed
      varying densities of beta-adrenergic receptor binding. In each region, the beta 2
      subtype was proportionally greater than the beta 1-subtype. Astrocytes also
      expressed a significant density of alpha 1-receptors. Trigeminal motor neurons
      did not show beta-receptor binding, but had a density of alpha 1-receptors
      tenfold greater than astrocytes. A model for the role of astrocytes in adrenergic
      receptor-mediated modulation of trigeminal motor neuron excitability is
      discussed.

PMID- 1393603
TI  - Autonomic control of neuronal-astrocytic interactions, regulating metabolic
      activities, and ion fluxes in the CNS.
AB  - It is generally assumed that the brain, in contrast to all other organs, is not
      equipped with an autonomic nervous system, regulating blood supply, and cellular
      activities. This may be because systemic administration of most drugs acting on
      monoaminergic or cholinergic receptors have little or no effect on cerebral blood
      flow and metabolism. However, intrathecal administration of noradrenaline does,
      indeed, influence both blood flow and energy metabolism in the brain. The present
      review focuses on effects of noradrenaline or serotonin on energy metabolism,
      turnover of amino acid transmitters and ion homeostasis, with special emphasis on
      the cellular localization. Noradrenergic agonists stimulate brain metabolism in
      vivo as well as many aspects of energy metabolism, Na+,K(+)-ATPase activity and
      uptake of transmitter amino acids in astrocytes in primary cultures, with little
      or no effect on corresponding preparations of neurons. Serotonin acts
      differently, decreasing potassium-induced release of glutamate from both neurons
      and astrocytes. Little is known about the effects of acetylcholine. The
      functional significance of these effects is discussed.

PMID- 1393604
TI  - Alteration of neuronal responses in the subthalamic nucleus following globus
      pallidus and neostriatal lesions in rats.
AB  - Kainic acid (2-4 days) or ibotenic acid (7-9 days) lesions of the globus pallidus
      or neostriatum altered the responsiveness of subthalamic nucleus neurons to
      electrical stimulation of the agranular frontal cortex. Three changes in
      responsiveness were seen following pallidal lesion: a) An increase in the
      proportion of responding cells as compared to controls (approximately 90% vs.
      60%); b) an increase in the total duration of the evoked response (62.5 ms vs.
      28.6 ms); 3) an increase in magnitude of response (9.76 spikes per stimulus vs.
      3.24). Both an increase in firing rate (17.94 spikes/s vs. 8.23) and a change to
      a bursty spontaneous firing pattern were seen. Lesion of the neostriatum had
      fewer but opposite effects including decreased firing rate (7.21 spikes/s) and
      decreased total response duration (18.9 ms). These results suggest that the
      normal tonic inhibition of the subthalamic nucleus by the globus pallidus may
      play an important role in controlling subthalamic neuronal spontaneous activity
      and responsiveness. The neostriatum may influence the subthalamic nucleus via the
      globus pallidus. Globus pallidus lesions may have important consequences on the
      specificity of cortical control of the subthalamic nucleus and may alter
      subthalamic influence on basal ganglia output.

PMID- 1393605
TI  - GABA levels and GAD immunoreactivity in the deep cerebellar nuclei of rats with
      altered olivo-cerebellar function.
AB  - Immunocytochemistry was used to examine the distribution, size, and density of
      glutamic acid decarboxylase immunoreactive (GAD+) puncta in two animal models
      with movement disorders, the genetically dystonic (dt) rat and rats with 3
      acetylpyridine (3AP) lesions of the inferior olive. In both models, GAD activity
      is increased in the deep cerebellar nuclei (DCN) where the enzyme is localized
      primarily in the terminals of Purkinje cells. GABA levels were also measured in
      the DCN. The general distribution of GAD+ puncta in the DCN was similar in all
      groups. Immediately after the 3AP lesions, however, GABA levels were elevated in
      3AP rats in comparison with both normal rats and age-matched dt rats. GAD+ puncta
      were also larger than normal in the 3AP group at this time, although the
      magnitude of this effect declined over a 2-week recovery period. Puncta density
      was decreased in the medial nucleus only in 25-day-old dt rats in comparisons
      with normal littermates. These findings are discussed in the context of
      previously reported differences in the firing rate of Purkinje cells in dt and
      3AP-treated rats.

PMID- 1393606
TI  - Quantitative trait loci associated with brain weight in the BXD/Ty recombinant
      inbred mouse strains.
AB  - Adult C57BL/6J (B6) male mice had 37% heavier brains than did DBA/2J (D2) mice,
      while their body weights did not differ. The BXD recombinant inbred (RI) series
      of 20 strains, derived from a cross between B6 and D2 inbred strains, was used as
      the initial screen to determine significant associations between male brain
      weight and brain:body weight ratio, with allelic variation at 360 known marker
      gene loci. For brain weight, this yielded five candidate chromosome regions, each
      reflecting a possible quantitative trait locus (QTL) site affecting brain weight.
      The second step was to test as many of these five as possible using standard (non
      RI) inbred strain data for brain weight previously reported in the literature.
      For this purpose, only strains possessing the same alleles as the B6 or D2
      strains were used. Sufficient data to test two of the five candidate QTL were
      available. Of these, one was strongly supported as a site affecting brain weight-
      the D7rp2 region of chromosome 7. For the brain to body weight ratio, four
      chromosome regions emerged as significantly associated in the BXD series, but
      none were amenable to testing due to a lack of allelic information for the
      standard inbred strains. However, two of these regions showed highly significant
      associations (p less than 0.001, single test) that merit consideration as QTL
      sites for future testing. These two are the Hba region on chromosome 11 and the
      D17Tu7 region on chromosome 17. The genetic correlation between brain and body
      weight was low (r = 0.28), indicating that these two traits are largely
      genetically independent in the BXD RI series.

PMID- 1393607
TI  - Place and taste aversion learning: role of basal forebrain, parietal cortex, and
      amygdala.
AB  - Animals with nucleus basalis magnocellularis (NBM), parietal cortex, dorsolateral
      frontal cortex, amygdala or control lesions were tested in a neophobia and taste
      aversion learning task. Only animals with basolateral amygdala lesions were
      impaired in taste aversion learning and in displaying neophobia to a novel
      flavor. This finding suggested a dissociation between the function of the NBM
      component of the basal forebrain cholinergic system and the amygdala. The same
      animals with NBM or control lesions were then tested for acquisition of a spatial
      navigation task using a dry-land version (cheese board) of the Morris water maze.
      Animals with NBM lesions were impaired in this task relative to control animals.
      Animals with parietal cortex lesions displayed a comparable deficit in the place
      navigation task. These findings suggest parallel functions for the NBM component
      of the basal forebrain system and the parietal cortex. The role of the NBM in
      mediating memory appears to be limited in that it does not play a role in all
      learning situations.

PMID- 1393608
TI  - A reexamination of the effects of intracerebroventricular glucocorticoids in
      adrenalectomized rats.
AB  - Several investigators have reported that many of the behavioral and metabolic
      effects of ADX can be reversed by appropriate levels of glucocorticoids
      administered either peripherally or centrally. The present studies were conducted
      to offer a comparison of the effects of orally administered corticosterone (CORT)
      with ICV glucocorticoids [CORT, CORT acetate, or dexamethasone (DEX)]. Of
      particular interest were the effects of glucocorticoid treatment on body weight
      gain and on macronutrient self-selection. Adult male Sprague-Dawley rats were
      fitted with ICV cannulae and either bilaterally ADX or given sham operations. In
      the first experiment, ADX animals were initially treated systematically with CORT
      (20 micrograms/ml in their drinking water). After a wash-out period during which
      no steroids were administered, ADX rats were given daily ICV CORT injections (100
      micrograms/day in 10 microliters). Systemic CORT treatment promotes weight gain
      and normal food choice patterns in ADX rats. ICV injections failed to promote
      weight gain in ADX rats, and daily injection of the vehicle promoted a weight
      loss in sham-operated controls. Four additional experiments were conducted. ADX,
      glucocorticoid-treated animals and ADX, vehicle-treated controls as well as sham
      operated, vehicle-treated controls were used to assess the effects of both
      steroid and vehicle on body weight gain and dietary selection patterns. ADX ICV
      glucocorticoid-treated animals typically failed to gain weight at the rate
      observed when ADX rats are treated with CORT systematically. Under one condition,
      ADX-CORT-treated animals gained weight at a rate comparable to untreated
      controls, but their ICV-injected control group failed to gain weight.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1393609
TI  - Alterations in hippocampal cholinergic receptors and hippocampal behaviors after
      early exposure to nicotine.
AB  - Mice were exposed to nicotine prenatally by injecting the mother with 1.5 mg/kg
      nicotine SC twice daily on gestation days 9-18 (PreN mice) or neonatally by daily
      SC injections of 1.5 mg/kg nicotine on postnatal days 2-21 (NeoN mice). At age 50
      days, hippocampal muscarinic receptors Bmax of PreN and NeoN mice were 58% and
      79% above control, respectively (p less than 0.01); Kd was unaffected by early
      nicotine exposure. Eight-arm maze performance of nicotine-exposed animals fell
      behind control level. Both PreN and NeoN made approximately 10% less correct
      responses in the first eight trials than controls throughout the test period (p
      less than 0.01). By the last day of testing, PreN needed 23% and NeoN 31% more
      trials than controls to enter all arms (p less than 0.001). In addition, PreN
      needed 35 and NeoN 42% more days than controls to reach criterion (p less than
      0.05). Similarly, while 61% of controls reached criterion by day 6 only 17% of
      PreN and 25% of NeoN reached criterion (p less than 0.01). In the Morris maze,
      PreN needed from 43-119% more time to reach the platform (p less than 0.001). In
      the spatial probe test, PreN animals made 35% fewer crosses over the area of the
      missing platform (p less than 0.001). The study suggests that nicotine
      administered to the fetus or neonate alters septohippocampal chemistry and
      induces deficits in hippocampus-related behaviors. The possible reversal of the
      behavioral changes by manipulating the cholinergic innervations should be the
      subject of future investigations.

PMID- 1393610
TI  - Hypothalamic lesions increase neuronal immunoreactivity for neuropeptide Y.
AB  - An enhanced production of hypothalamic neuropeptide Y (NPY) now appears to
      underlie a number of hyperphagia syndromes. However, the role of NPY in the
      hyperphagia induced by hypothalamic lesions has not yet been explored. Here,
      hypothalamic lesions were induced in mice by administration of goldthioglucose
      (GTG) and brain sections were stained immunocytochemically for NPY without
      pretreatment with colchicine. NPY-immunoreactive somas were visible in the
      hypothalamus of only one of eight control mice but were identified in the
      hypothalami of six of seven mice with GTG lesions. This suggests that GTG lesions
      cause an enhanced production of NPY, perhaps due to interruption of fibers from
      arcuate dopaminergic neurons that normally inhibit NPY+ cells. Thus, hypothalamic
      lesions may provoke hyperphagia by stimulating the production of NPY.

PMID- 1393611
TI  - Behavioral consequences in animal tests of anxiety and exploration of exposure to
      cat odor.
AB  - Rats exposed to a cloth impregnated with cat odor showed a decreased number of
      contacts with the cloth and time in contact with it and increased time sheltering
      from it. Exposure to the odor of rat blood produced similar, though less marked,
      changes and also increased the number of occasions the rat sought shelter.
      Exposure to the odor of disinfectant changed only the time in contact with the
      cloth. Exposure to cat odor also resulted in anxiogenic responses in the social
      interaction and elevated plus-maze tests that could be detected up to 1 h, but
      not 24 h, after odor exposure. Decreased exploration in the holeboard could also
      be detected up to 1 h, but not 24 h, after exposure to cat odor. The time in
      contact with the cloth, the incidence of, and time spent sheltering did not
      decrease over five successive exposures to the odor of a cat. The number of
      contacts with the control odor cloth increased over successive exposures, but
      contacts with the cat odor cloth did not change over successive exposures. The
      decreased exploration in the holeboard, as a result of prior exposure to cat
      odor, showed rapid habituation, as did the anxiogenic response detected in the
      social interaction test, whereas that detected in the plus-maze persisted for up
      to five odor exposures.

PMID- 1393612
TI  - Effect of nonpeptide angiotensin receptor antagonists on water intake and salt
      appetite in rats.
AB  - Nonpeptide angiotensin AT-1 and AT-2 receptor antagonists were administered
      cerebroventricularly to rats and their effects on various types of angiotensin II
      (AII)-stimulated water and NaCl intakes examined. The AT-1 receptor blocker,
      losartan potassium (DUP 753), inhibited water intake evoked by central
      administration of AII, with the 50% inhibitory dose being less than 0.1
      microgram. The functional inhibition by higher doses lasted at least 1 h. The AT
      2 receptor antagonist PD 123319 also inhibited AII-induced water intake, but at
      doses about tenfold higher than losartan. Central, but not peripheral,
      administration of losartan partially inhibited NaCl intake induced by either
      sodium depletion, treatment with angiotensin converting enzyme inhibitors (CEIs),
      or adrenalectomy. PD 123319 partially inhibited NaCl intake induced by both
      sodium depletion and administration of CEI, but not after adrenalectomy. Another
      AT-2 receptor antagonist, CGP 42112A, likewise inhibited NaCl intake after sodium
      deprivation. These data suggest that both AT-1 and AT-2 receptor subtypes in the
      brain are involved in angiotensin-related water and NaCl intakes.

PMID- 1393613
TI  - Artificial rearing alters development of the nucleus of the solitary tract.
AB  - Previous studies have shown that damage induced to fungiform papillae of the
      anterior tongue at postnatal day 2 (P2) alters both pre- and postsynaptic
      development of gustatory recipient zones within the rostral nucleus of the
      solitary tract (NST). The present study was conducted to determine whether or not
      artificial rearing (AR) manipulations, which reduce normal orochemical
      stimulation during early postnatal development, would be sufficient to produce
      alterations in anatomical development of the rostral gustatory NST. Two groups of
      Long-Evans hooded rats were examined. One group received normal rearing with a
      lactating dam from birth to weaning (mother reared; MR). A second group of
      animals received artificial rearing via intragastric cannulae between the ages of
      P4 and P14, and were thereafter returned to lactating dams until the age of
      weaning (P21). Following weaning and maturation to adulthood (P49), the
      organization of gustatory afferent terminal fields in the NST was examined using
      fluorescent tracing procedures which permit the simultaneous visualization of
      gustatory afferent terminal fields arising from the seventh and ninth cranial
      nerves. Results show that AR manipulations between the ages of P4 and P14 produce
      alterations in development of gustatory afferent terminal fields in the NST that
      are essentially similar to those observed following early postnatal receptor
      damage. These results confirm previous suggestions that orochemical stimulation
      during a limited portion of rats' postnatal life is essential in inducing normal
      presynaptic development in the gustatory NST.

PMID- 1393614
TI  - Overlapping visual fields and ipsilateral retinal projections in turtles.
AB  - The possible relationship between overlap of the visual fields and the importance
      of ipsilateral retinal projections was investigated in the two Chelonian genera
      Chinemys and Trionyx. Of these two species, Trionyx has more frontally located
      eyes, yet ipsilateral retinal projections could not be demonstrated by
      radioautography. In Chinemys, on the other hand, the ipsilateral retinothalamic
      projections are extensive. It is suggested that, in contrast to Trionyx, the
      anatomic substrate of stereoscopic vision in Chinemys may be similar to that in
      mammals.

PMID- 1393615
TI  - Cerebellar norepinephrine infusions facilitate recovery after sensorimotor cortex
      injury.
AB  - This study reports the effects of norepinephrine infusions into cerebellum after
      unilateral sensorimotor cortex injury. The results demonstrate an immediate and
      permanent acceleration in motor recovery in awake rats infused with 150
      micrograms norepinephrine into the cerebellum contralateral to a right
      sensorimotor cortex ablation. A vehicle infusion or infusion of norepinephrine
      into the ipsilateral cerebellum produced no beneficial effects on functional
      recovery.

PMID- 1393616
TI  - A computer-assisted direct-imaging system to obtain numerical densities of
      neurons in human cortex.
AB  - Studies of the numerical density of microscopic items in brain tissue is a time
      consuming endeavor. However, such information is important for numerous issues
      such as the relationship between structure and function in the normal brain,
      individual differences, and studies of brains of neuropsychiatric patients. A
      computer-assisted imaging system specifically devised to obtain estimates of
      numerical densities in human cortex is described here. Its main advantage is that
      the microscopist can analyze the original image directly under the microscope,
      and most aspects of data acquisition and quantitative analysis are accomplished
      by the computer. The key features of the system are a Microvid (an electronic
      camera lucida) and the use of X, Y, and Z stage encoders in conjunction with
      three-dimensional computer software. The complete system is relatively
      inexpensive and is simple to set up and use. The reliability and validity of the
      numerical densities obtained using this system are documented.

PMID- 1393618
TI  - Ultrastructure of cholinergic neurons in the laterodorsal tegmental nucleus of
      the rat: interaction with catecholamine fibers.
AB  - The ultrastructure of choline acetyltransferase (ChAT)-immunoreactive neurons in
      the laterodorsal tegmental nucleus (TLD) of the rat was investigated by
      immunohistochemical techniques. The immunoreactive neurons were medium to large
      in size, with a few elongated dendrites, contained well-developed cytoplasm, and
      a nucleus with deep infoldings. They received many nonimmunoreactive, mostly
      asymmetric synaptic inputs on their soma and dendrites. ChAT-immunoreactive,
      usually myelinated, axons were occasionally seen in TLD. Only one immunoreactive
      axon terminal was observed within TLD, and it made synaptic contact with a
      nonimmunoreactive neuronal perikaryon. The synaptic interactions between ChAT
      immunoreactive neurons and tyrosine hydroxylase (TH)-immunoreactive fibers in the
      TLD were investigated with a double immunohistochemical staining method. ChAT
      immunoreactivity detected with a beta-galactosidase method was light blue-green
      in the light microscope and formed dot-like electron dense particles at the
      electron microscopic level. TH-immunoreactivity, visualized with a nickel
      enhanced immunoperoxidase method, was dark blue-black in the light microscope and
      diffusely opaque in the electron microscope. Therefore, the difference between
      these two kinds of immunoreactivity could be quite easily distinguished at both
      light and electron microscopic levels. In the light microscope, TH-positive
      fibers were often closely apposed to ChAT-immunoreactive cell bodies and
      dendrites in TLD. In the electron microscope, the cell soma and proximal
      dendrites of ChAT-immunoreactive neurons received synaptic contacts from TH
      immunoreactive axon terminals. These results provide a morphological basis for
      catecholaminergic regulation of the cholinergic reticular system.

PMID- 1393617
TI  - Kainic acid-induced seizures in aged rats: neurochemical correlates.
AB  - This study was conducted to assess the functional integrity of the kainate
      receptor-mediated seizure response in aged rats. Kainic acid was administered
      systemically to aged female Long-Evans (LE) rats and aged male F344 rats and the
      proconvulsant actions of kainic acid was compared to adult controls. The effects
      of kainic acid on brain regional content of monoamines and amino acids was also
      determined in the aged female LE and adult control rats. The latency to full
      clonic-tonic seizures was significantly reduced in aged female LE rats, and the
      number of seizures was significantly increased above that of the controls. There
      was increased mortality and a reduction in the latency to exhibit wet dog shakes
      in the aged F344 rats. Studies were also conducted to evaluate the role of
      ovarian hormones, route of administration, and dose of kainic acid in mediating
      the enhanced proconvulsant actions of kainic acid in aged rats. The neurochemical
      studies suggested that kainic acid significantly enhanced the release of ASP,
      GLU, and norepinephrine (NE) in the aged rats exhibiting clonic-tonic seizures.
      The adult rats given the same dose of kainic acid (15 mg/kg, IP) did not exhibit
      any significant change in brain content of monoamines or amino acids except for a
      reduction in mediobasal hypothalamic NE. An in vitro study was also conducted
      using brain slices from adult and aged F344 and it was found that aged rats
      released significantly more ASP than adults in response to kainic acid. These
      neurochemical findings were discussed in relation to previous studies of age
      related alterations in excitatory amino acids (EAAs) and the role of EAA and NE
      in modulating limbic seizures. This study has clearly demonstrated that aged rats
      may be more susceptible to the excitotoxic action of EEAs acting through kainetic
      receptors.

PMID- 1393619
TI  - Do callosal projection neurons reflect sex differences in axon number?
AB  - We have reported that female rats have more axons in the splenium of the corpus
      callosum than do male rats (12). To determine if the greater number of axons
      found in female rats might be reflected in a larger distribution of callosal
      projection neurons, horseradish peroxidase (HRP) was injected into the visual
      cortex of 55-65-day-old rats of both sexes that had been housed in a complex
      environment since weaning. The pattern of labeled neurons was examined in
      tangential sections in the cortex contralateral to the injection site, and three
      dimensional reconstructions were quantified at the area 17/18a border and in area
      18b. Male and female rats were found to have indistinguishable distributions of
      labeled callosal projection neurons. The present study failed to find an obvious
      difference in the distribution of projection neurons as the basis for the sex
      differences in axon number, but because of the limitations of tracing techniques,
      subtle differences cannot be excluded.

PMID- 1393620
TI  - Determination of free calcium.
AB  - A computer program designed to be user friendly is described in this report. Two
      types of calculations are provided: a) determination of free calcium
      concentration based on known total salt concentration and b) those which
      calculate total salt concentration required to insure a desired free calcium
      concentration in the buffered system. The user can choose up to 10 different
      ligands, nine different cations (known total concentration) and 10 concentrations
      (either free or total) of the variable cation (e.g. calcium) per calculation.
      Thus, this program does not restrict its user to one or two parameters (e.g.,
      buffer and/or ions). Data generated using this method are in excellent agreement
      with those derived using programs in current use.

PMID- 1393621
TI  - Responses of lateral hypothalamic neurons recorded in vitro to moderate changes
      in glucose concentration.
AB  - Single unit neuronal activity of lateral hypothalamic neurons was recorded
      extracellularly in hypothalamic slices. Glucose concentration in the perfusate
      was modified in small amounts to simulate normal physiological glycemic
      fluctuations associated with feeding. Several neurons responded reliably under
      these conditions. These data on simulated small glycemic changes, based on
      observations in the whole animal, suggest that the modulation of neuronal
      activity reported in this study is a result of a direct action of glucose on
      cells in this region of the hypothalamus.

PMID- 1393622
TI  - Thermally evoked tail avoidance reflex: input-output relationships and their
      modulation.
AB  - Latency to onset and magnitude (angular displacement) of thermally evoked tail
      avoidance reflexes (TETAR) to graded thermal stimuli were measured in
      pentobarbital-treated and untreated rats. The latency to onset was inversely and
      the magnitude was directly proportional to the thermal stimulus intensity.
      Pentobarbital prolonged the latency to onset of the TETAR to low by not high
      stimulus intensities. Activation of (-)-nicotine sensitive brainstem hyperalgesic
      processes shortened the latency and increased the magnitude of the TETAR. The
      hyperalgesic actions of (-)-nicotine were most demonstrable at lower thermal
      stimulus intensities. These studies suggest that the TETAR is graded in intensity
      as the stimulus intensity is increased and that the response evoked by different
      intensities of stimulus probably involve common neurophysiologic mechanisms.

PMID- 1393623
TI  - Epileptogenic activity in the amygdala is not affected by the amidine steroid, R
      5135.
AB  - The synthetic steroid amidine 3-alpha-hydroxy-16-imino-5-beta-17aza androstan-11
      one (R 5135) is known to elicit long-lasting spiking in the cortex in the
      presence of neocortical damage. R 5135 administered to amygdaloid-kindled and
      naive rats resulted in regular, high-amplitude spiking in the cortex but only
      occasionally elicited small-amplitude spikes in the amygdala (AMY) and
      hippocampus (HPC). Interictal spikes from the AMY of kindled rats were not
      synchronized with cortical spikes induced by the steroid. Given that R 5135 is
      known to be a GABAA receptor antagonist, these findings suggest that GABAA
      receptors in AMY and HPC may have lower affinity for 3 alpha-hydroxysteroids.

PMID- 1393624
TI  - Some solvents for antiepileptics have proepileptic potencies in the WAG/Rij rat
      model for absence epilepsy.
AB  - Some solvents for antiepileptics were tested, for 4 consecutive days, in a rat
      model (the WAG/Rij inbred strain) for absence epilepsy. Electroencephalogram
      registrations and behavioral observations suggested that both Tween-80 and a
      mixture of saline/ethanol/propylene glycol caused an increase in the number of
      epileptic phenomena. This increase was not significant and restricted to
      injection day 1 with Tween-80 but was significantly present during all 4
      injection days with the saline/ethanol/propylene glycol mixture. Furthermore,
      with this latter solvent the increase became larger during consecutive days.
      Because of the proepileptic potencies and the differential time effects of these
      solvents, their usage should be seriously questioned.

PMID- 1393626
TI  - Eutanazia v Holandsku: diskusia a prax. [Euthanasia in Holland: discussion and
      practice].

PMID- 1393627
TI  - [Plasma cholesterol levels and ischemic heart disease: new findings and new
      approaches].
AB  - The information explosion characteristic of recent years has presented a series
      of findings enabling a more effective prevention of ischemic heart disease by
      controlling low density lipoprotein (LDL) levels of cholesterol. The detection of
      LDL receptors has provided new information on the mechanisms regulating the level
      of plasma LDL. Data on competitive inhibitors of endogenous cholesterol synthesis
      have afforded new possibilities of pharmacological control of LDL levels. Studies
      of primary prevention of ischemic heart disease have yielded evidence showing
      that a 1% decrease of cholesterol level reduces coronary risk by 2%. A
      prospective study of the relationship between cholesterol levels and coronary
      mortality, absolutely unique as to its extent (368,000 middle-aged men followed
      up over a period of 6 years) has demonstrated that there is no borderline
      cholesterol level below which coronary risk would be absolutely excluded. Between
      total cholesterol level and coronary mortality there is a close, continual and
      graded relationship. In light of these findings, total cholesterol levels have
      been reclassified: desirable levels -5.2 x 10(-3) mol.l-1, borderline risk levels
      under 5.2-6.2 x 10(-3) mol.l-1, and high risk levels--above 6.2 x 10(-3) mol.l-1.
      In subjects with several risk factors (smoking, hypertension, familial occurrence
      of heart, heart disease, obesity, diabetes mellitus, HDL cholesterol below 0.9 x
      10(-3) mol.l-1) the level of total cholesterol should be brought down below 4 x
      10(-3) mol.l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393625
TI  - Calcium entry blocker ameliorates ischemic neuronal damage in monkey hippocampus.
AB  - Effects of treatment with (+/-)-1-(3,4-dimethoxyphenyl)-2-(4-
      diphenylmethylpiperazinyl)ethanol dihydrochloride (NC-1100), a calcium entry
      blocker, on ischemic neuronal damage were investigated. Monkeys were subjected to
      temporary occlusion of eight (bilateral common carotid, internal and external
      carotid, and vertebral arteries) major arteries. Blood flow was restored after 5,
      10, 13, and 15 min occlusion, and NC-1100 (1 mg/kg) was then immediately infused
      intravenously. Monkeys were killed by perfusion fixation 5 days after occlusion.
      All brain regions were then histologically investigated for ischemic neuronal
      changes. Physiological data of NC-1100-treated subjects were not significantly
      different than those of untreated subjects. Heart rate tended to decrease after
      ischemia in treated subjects. Occlusion of 8 arteries for 10 to 15 min produced
      ischemic neuronal damage confined exclusively to the CA1 subfield of the
      hippocampus. Treatment with NC-1100 markedly reduced ischemic neuronal damage in
      the CA1 subfield of the hippocampus. It is suggested that postischemic treatment
      with the calcium entry blocker, NC-1100, might protect the brain from the
      ischemic damage produced in patients suffering from transient ischemia.

PMID- 1393628
TI  - [Rapid prenatal diagnosis of cystic fibrosis using the polymerase chain reaction:
      results of the first 5 cases].
AB  - Cystic fibrosis (CF) is an autosomal recessive lethal disease with an incidence
      in Slovakia of 1 affected in 1800 newborns. Within a year the incidence amounts
      to about 50 cases. Though the responsible gene has already been cloned, the only
      effective approach to prevention is prenatal diagnosis in the first and second
      trimester of pregnancy. The paper presents the results of the first five cases of
      prenatal diagnosis of CF established by the new rapid method of DNA analysis,
      polymerase chain reaction (PCR). Delta F508 deletion mutation and closely linked
      DNA polymorphism KM19/PstI were assessed. In two of the five cases studied the
      fetuses were found to be affected and pregnancy termination was indicated. To
      exclude the possibility of fetal DNA contamination with maternal DNA, the
      hypervariable DNA polymorphism VNTR apoB was determined simultaneously. The
      advantages of this approach are demonstrated on cases of prenatal diagnosis
      performed in two families where contamination of fetal DNA could be excluded. The
      value of the PCR method is being compared with that of Southern's hybridization
      method. (Tab. 2, Fig. 4, Ref. 27.).

PMID- 1393629
TI  - [Incidental detection of coronary artery anomalies].
AB  - A retrospective study is presented analyzing the clinical findings in 15 patients
      in the age range of 18-58 years (12 men, 3 women) with anomalous origin of the
      coronary arteries diagnosed from 5500 coronary arteriograms performed in the
      authors' institute IKEM. In 4 patients the anomaly was isolated, in 11 patients
      associated, and that in 6 with coronary disease, in 3 with rheumatic disease, and
      in 2 patients with atrial septal defect. Although the disease is congenital, its
      manifestations appeared only in the 16th to 54th year of life, presenting a
      nonspecific clinical picture, physical, ECG and XR findings. Changes in the
      ergometric test and left ventriculography were determined by the associated
      disease. Diagnosis of the anomaly was established by selective coronarography.

PMID- 1393630
TI  - [The effect of cyclophosphamide and methotrexate on gastric emptying and
      secretion in rats].
AB  - The effect of cyclophosphamide and methotrexate was studied in rats on the
      evacuation of 50% BaSO4 suspension from the stomach (doses: 50-200 mg.kg-1 and 5
      20 mg.kg-1 s.c.) and on HCl secretion (doses: 100 mg.kg-1 and 10 mg.kg-1 s.c.)
      after stimulation with pentagastrin (25 micrograms.kg-1 s.c.). Both cytostatics
      were found to slow down gastric evacuation and to suppress the effect of
      pentagastrin on gastric secretion. The presented changes may relate to the
      adverse effects on the GIT observed in patients treated with the given
      cytostatics. (Fig. 4, Ref. 17.)

PMID- 1393631
TI  - [Professor Antonin Spilka in the history of the Comenius University Medical
      School in Bratislava].
AB  - Professor MUDr. Antonin Spilka was one of the outstanding personalities of the
      Medical Faculty of Comenius University in Bratislava in the first years of its
      existence. He was among the first Czech medical doctors who came to Bratislava
      and was among the last ones to leave it. In 1919 he was substantially involved in
      the establishment of the Institute of Morbid Anatomy and he was its Head till
      1926. In the period from 1927 to 1938 he was Head of the Institute of Medical
      History, Philosophy, and Hodogetics. Prof. Spilka was first Deputy Dean then he
      became Dean of the Faculty and over many years he was actively engaged and held
      various academic positions in different faculty and university institutions.
      Stricken by a severe disease in 1926, he nevertheless remained active focusing
      his interest on history of medicine and health care and end medical ethics.

PMID- 1393633
TI  - [Bacterial resistance to aminoglycoside antibiotics].
AB  - Aminoglycoside antibiotics, such as gentamicin, netilmicin, tobramycin, amikacin,
      may be inactivated by resistant bacteria producing three types of enzymes: O
      nucleotidyltransferases, O-phosphotransferases and N-acetyltransferases.
      Mechanisms of aminoglycoside resistance were analyzed in clinical isolates of
      gram-negative bacteria from several regions of Czecho-Slovakia and compared with
      the use of aminoglycosides. Production of acetyltransferases (AAC) and
      nucleotidyltransferases (ANT) was observed in 84% of bacterial isolates. The
      majority of bacterial strains studied produced the AAC/3/enzyme (62%). Due to
      dissemination of plasmids coding for the AAC/3/enzyme, the majority of Czecho
      Slovak gentamicin-resistant strains was also tobramycin resistant (93%) and
      netilmicin resistant (68%). Amikacin remains the most effective aminoglycoside
      antibiotic against multiresistant bacterial strains.

PMID- 1393632
TI  - Changes in levels of thyroid hormones and TSH in acute myocardial infarction.
AB  - The changes in levels of total serum thyroxine (T4), total serum triiodothyronine
      (T3), effective thyroxine ratio (ETR), and serum TSH were investigated in 88
      patients with acute myocardial infarction (AMI). The T4 and T3 values decreased
      significantly on the third day of hospitalization to return to starting values on
      the 7th day. ETR values were significantly reduced on the 3rd day and remained so
      also on the 7th day. Compared to starting values, serum TSH levels were increased
      on the 7th day of hospitalization, yet not significantly. In the group of 16
      patients who died within 96 hours, ETR values were significantly increased on the
      1st day of hospitalization (immediately after admission) in comparison with the
      group of AMI surviving patients. The highest frequency rate of abnormally low T3
      values was found in patients who died within 96 hours. With respect to thyroid
      function evaluation, ETR proved to be the most satisfactory parameter with the
      lowest percentage of abnormal values.

PMID- 1393634
TI  - [The role of mitochondrial energy metabolism and oxygen free radicals in the
      pathogenesis of experimental autoimmune myocarditis].
AB  - In a model of autoimmune myocarditis in guinea piga, the authors studied energy
      producing processes in mitochondria and the role of oxygen free radical
      generation in tissue injury. A significant decrease in the capacity of oxidative
      phosphorylation was detected in parameters QO2 (S3) on the basis of glutamate +
      malate (p < 0.005) and pyruvate (p < 0.05) measurements. Other parameters studied
      were however only insignificantly reduced in myocarditic heart mitochondria as
      compared to controls. The activity of mitochondrial cytochrome oxidase was also
      insignificantly reduced in animals with myocarditis. Generation of oxygen free
      radicals was in the presence of the inflammatory infiltrate in this model not
      significantly higher than in the intact myocardial tissue.

PMID- 1393636
TI  - [Is there a relation between cardiorespiratory fitness and systolic time
      intervals?].
AB  - Systolic time intervals measured by polycardiography significantly correlated
      with some spiroergometric parameters of cardiorespiratory fitness both at rest
      and during dynamic exercise. The correlations were mostly free. There were
      considerable intraindividual differences. The method of polycardiography can thus
      not be recommended for exact intraindividual differentiation of left vetricular
      functional ability. Intraindividual detection of systolic time intervals will be
      the subject of our further investigation.

PMID- 1393635
TI  - [Prophylactic administration of selected antibiotics in hospitals in the Slovak
      Republic].
AB  - Over a period of ten years prophylactic administration of selected antibiotics
      was evaluated three times (in 1973, 1983, and in 1988) in the same ten hospitals
      of the Slovak Republic. The study was focused on the use of gentamicin (GEN),
      cotrimoxasol (COT) and cephalosporins (CEP). Prophylactic administration of
      antibiotics was found to be increasing. GEN is being given less frequently, while
      CEP are administered more often, which is considered to be a positive trend. The
      period of prophylactic administration of antibiotics is still inadequately long
      with an average of 10.7 days. Evaluation of antibiotic administration showed that
      antibacterial substances have the highest rate of prophylactic administration in
      patients with oncologic diseases, followed by patients with diseases of the
      urinogenital system. A positive development was recorded in the perinatal period
      with a decreasing trend in the prophylactic administration of antibiotics.

PMID- 1393637
TI  - [Surgical treatment of supravalvular aortic stenosis].
AB  - Over the last 22 years, two children were operated on for supraventricular aortic
      stenosis at the Institute of Cardiovascular Diseases in Bratislava. Both cases
      presented a localized form of supravalvular aortic stenosis. Simple elipsoid
      flaps were used without extended aortoplasty. One of the two children, a 12-year
      old boy with Williams' syndrome died of endocarditis in the early postoperative
      period. In the 10-year-old girl with familial supravalvular aortic stenosis the
      operation was successful, although the defect was combined with supravalvular
      muscular obstruction. The authors emphasize the possibility of choice between two
      surgical procedures according to the localization of the stenosis with respect to
      the valvular apparatus.

PMID- 1393638
TI  - [The effect of streptozotocin diabetes on lipid levels in the myocardium in young
      rats].
AB  - The effect of intraperitoneally administered streptozotocin was studied in 8-, 10
      , and 12-week-old rats. The total triacylglycerol content was found to be
      significantly increased in all the three groups studied, and that by 59.64% in
      the 8-week old group, by 54.86% in the 10-week-old group, and by 50.57% in the 12
      week-old group. The level of total phospholipids increased only in the 8-week-old
      group of diabetic animals, and that by 11.09%, whereas in the other age groups
      studied it remained unchanged. In the level of individual phospholipids changes
      occurred in 8-week-old rats, namely phosphatidylcholine increased by 53.0% and
      sphingomyelin by 23.8%. In 10- and 12-week-old diabetic rats the only change was
      recorded in the level of cardiolipin which increased by 54.23% in 12-week-old
      animals.

PMID- 1393639
TI  - [The activities of Professor Alojz Chura at the Comenius University Medical
      School in Bratislava].
AB  - One of the most outstanding personalities of Slovak nationality acting at the
      Medical Faculty of Comenius University in the first two decades of its existence
      was Prof. MUDr. Alojz Chura. He was among the first students of the Faculty and
      was then its active member until 1945. The aim of the present study was to
      contribute to a better understanding and unbiased evaluation of the importance
      and impact of the activities of this remarkable personality of Slovak pediatrics.
      In 1925 MUDr. Chura started to work at the Teaching Hospital of Pediatrics and in
      1945 he was forced to leave both his position of Director of the Hospital and
      that of Full Professor of Pediatrics. As Director he had succeeded Prof. Brdlik
      who on leaving for Prague had suggested Prof. Chura for this responsible
      position. The contribution of Prof. Chura to the development of pediatrics in
      Slovakia was exceptional. His extensive sociological study "Slovakia without the
      Young Generation" laid the basis of social pediatrics in Slovakia. The Teaching
      Hospital of Pediatrics experienced considerable development under his guidance
      and that in all its areas of activity, i.e. teaching, prevention, therapy, and
      research. Besides his manifold activities at the Hospital and Medical Faculty,
      Prof. Chura was involved in many pursuits, particularly those which were related
      to the car of the youngest generation. He was Chairman of the Association of
      Pediatricians in Slovakia for many years. The study analyzes also the Memorandum
      issued in 1935 which is an important document of the actual social and health
      conditions in the Slovak country.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393641
TI  - The hundredth anniversary of Prof. Ing. Dr. Frantisek Valentin's birth.

PMID- 1393640
TI  - Mood stabilizing effect of verapamil.

PMID- 1393642
TI  - [Relation between lipid-bound sialic acid in blood serum and plasma andin human
      tumors].
AB  - Athymic mice with transplanted osteosarcoma and carcinoma of the rectum were
      found to have increased blood plasma levels of lipid-bound sialic acid (LSA). To
      verify the applicability of the method of LSA determination, patients with cancer
      of the mammary gland, rectum, and colon were examined for their LSA level. The
      serum LSA level was significantly increased in patients with cancer of the
      mammary gland and rectum, compared to levels determined in the serum of healthy
      volunteers. The serum LSA level elevation was even more pronounced in patients
      with carcinoma of the colon. In patients with carcinoma of the colon who were in
      remission at the time of blood collection the serum LSA level was found to be
      reduced to control values.

PMID- 1393644
TI  - [Reference values of QRS-complex amplitude parameters in computer evaluation of
      Frank's orthogonal electrocardiogram].
AB  - In 123 healthy subjects (54 women and 69 men) in the age range from 7 to 72 years
      the x, y, z coordinates were determined along with the magnitude of instantaneous
      spatial QRS vectors of the orthogonal electrocardiogram according to Frank, and
      that in 10 ms intervals from the beginning of the QRS complex and eighths of the
      duration of QRS. The values of these parameters were computed by means of
      Pipberger's VAH program implemented in the computer SM3-20. The results are
      presented as means, standard error of means, median, interpercentile interval (2
      to 98 percentile) and confidence intervals.

PMID- 1393643
TI  - [The effect of extrarenal factors on certain functions of the kidney and urinary
      tract. A radionuclide study].
AB  - The authors present their experiences concerning the effect of extrarenal factors
      on the results of radionuclide examination. Functional and functional
      morphological examinations of the kidneys and urinary tract can be negatively
      affected particularly by emotional stress, orthostasis, dehydration, increased
      kidney motility, address administered drugs during examination (diuretics), drug
      treatment of the primary disease, muscular strain, cold, pain, increased pressure
      in the vicinity of the kidney, hypertension, hypotension, as well as further
      conditions. Radionuclide methods can objectify these processes, the given
      negative effects can however be presumed to occur also at other examination
      procedures of the kidney and urinary tract. The conditions of examinations have
      thus to be optimized and standardized. The examining physician has to know which
      drugs the patient is receiving and he has to know their effect on renal function.

PMID- 1393645
TI  - [Structural basis of appendiceal function in rabbits].
AB  - Enzymo-, immuno- and lactin-histochemical methods were used to study the
      structure of the rabbit appendix wall. The value of some structural components in
      the function of this part of the intestine is discussed. Some findings were
      documented electronmicroscopically. In addition to its resorptive function, the
      rabbit appendix is equipped with a potent defense mechanism against adverse
      environmental effects of the appendix content. Individual structures of this
      defensive barrier are closely characterized with regard to cellular equipment and
      possibilities of its morphological identification.

PMID- 1393647
TI  - [The beginning of cardiac surgery in Slovakia].

PMID- 1393646
TI  - [The importance of pulmonary angiography in the surgical treatment of congenital
      heart defects with a left-right shunt and pulmonary hypertension].
AB  - The studied series consisted of 14 patients with ventricular septal defect and
      pulmonary hypertension aged from 3 months to 15 years. Three examination methods
      were compared: (1) Invasive hemodynamic examination; (2) Pulmoangiographic
      examination by means of wedge peripheral pulmoangiography; (3) Histological
      examination of bioptic samples. Direct correlation was found to exist between
      mean PA pressure, PAR/m2, TPR/SR and pulmoangiographic records, in which the
      following parameters were evaluated: (a) length of the narrowing of the
      peripheral branch of the PA, (b) background opacity, (c) circulation time. The
      histological findings obtained in the bioptic samples corresponded practically in
      all cases with the hemodynamic and PAG findings. Only in two patients did the
      histological picture display a less severe degree of affection than found by PAG
      and hemodynamic examination. The obtained results suggest that in light of
      surgical indications, PAG can be considered a suitable and valuable supplementary
      method in assessing borderline findings of pulmonary hypertension in children
      with congenital heart defects and left-to-right shunt.

PMID- 1393648
TI  - [Vectorcardiographic features of right ventricular dilatation].
AB  - Axial McFee-Parungao lead system vectorcardiograms were obtained in 55 patients
      with type atrial septal defect, aged 3-24 years, prior to and in average 3 years
      after surgical repair of the defect. Changes of the QRS loop observed after
      intervention led to the conclusion that the vectorcardiographic signs of right
      ventricular dilatation consist of a rightward shift of the posteriorly orientated
      horizontal plane vectors at 50-70 ms of QRS, decrease of the magnitude of vectors
      around the 40th ms, no changes in the magnitude and orientation of the initial
      (10-30 ms) QRS vectors as well abnormal departures of the spatial VCG loop from
      its preferential plane even in the absence of other signs of right ventricular
      conduction impairment. The above abnormalities vanished after normalization of
      hemodynamics.

PMID- 1393649
TI  - [The accuracy of saccadic eye movements is associated with their horizontal and
      vertical direction].
AB  - Electro-oculagraphic, photo-oculographic, and magnetoelectro-oculographic methods
      were used to study and to compare the accuracy of 10 degrees saccadic movements
      of the eyes in dependence on their direction to the right, to the left, upwards
      and downwards. Leftward saccades in right-handers and rightward saccades in left
      handers proved to be more accurate compared to saccades in the opposite
      direction. This finding may be related to the functional asymmetry of the
      cerebral hemispheres. Downward saccades are inaccurate in comparison to upward
      saccades. Their inaccuracy is caused by overshooting the target. In the case of
      vertical saccades, the existence of different generators in the brain for
      triggering upward and downward saccades may play a role, along with a potential
      preprogramming of the change in the downward look into a sequence of two
      saccades. The obtained results emphasize the requirement of calibrating the
      electro-oculogram by saccades in that direction in which the analyzed eye
      movements are recorded.

PMID- 1393650
TI  - [The role of short and long latency reflexes in the small muscles of the hand in
      the diagnosis of movement disorders--an electrophysiology study].
AB  - EMG changes of short (SLR) and long latency reflex (LLR) responses to electric
      stimulation of digital nerves of the index finger were recorded from the
      interosseous dorsal muscle I during its slight isometric contraction.
      Abnormalities of SLR and LLR were found at least on one hand in 9 of 11 patients
      with nosologically different dysfunctions of the nervous system. SLR latency can
      yield information on lesions of the peripheral motoneuron. LLR latency proved to
      be a sensitive indicator of spinal and supraspinal lesions, and since it has also
      an efferent branch and, unlike SEP, it can detect also lesions of the descending
      corticospinal pathway. Prolonged SLR latency occurred frequently in s. m.
      Assessment of muscle reflexes is a valuable auxiliary method in identifying
      lesions of the peripheral and particularly of the central nervous system.

PMID- 1393651
TI  - [Comparison of the inhibitory effect of diltiazem on neurogenic contractions in
      the mesenteric arteries and veins].
AB  - The effect of diltiazem on the magnitude of isometric contractions induced by
      electric stimulation of intramural nerves (4Hz) was studied on isolated rings of
      the mesenteric artery and vein of the dog and rabbit. Diltiazem in concentrations
      of 10(-5) mol/l and above inhibited neurogenic contractions of the mesenteric
      artery and vein of the dog in a dose-dependent manner. Inhibition of contractions
      of the mesenteric vein was found to be more pronounced than that of contractions
      of the mesenteric artery. In the mesenteric vessels of the rabbit, diltiazem in
      concentrations of 10(-6) and above inhibited neurogenic contractions, and again
      more markedly in the veins than in the arteries. On comparing the inhibition of
      contractions in the two animal species studied, the contractions of the
      mesenteric vein of the rabbit were found to be more intensely inhibited than
      those of the dog vein. Diltiazem inhibited also phentolamine-resistant neurogenic
      contractions of the mesenteric artery. The established differences in the
      magnitude of neurogenic contraction inhibition may presumably be accounted for by
      quantitative differences in adrenergic innervation of mesenteric arteries and
      veins, as well as by differences in the magnitude of the contraction component
      dependent on extracellular calcium which is greater in the veins than in the
      arteries. This may also explain the more pronounced inhibition of neurogenic
      contractions in the veins compared to arteries.

PMID- 1393652
TI  - [Vectorcardiography of variations in localization of specific conduction systems
      in the left ventricle].
AB  - A realistic computer model of propagation of ventricular activation was used to
      study the effects of varying the position of specific conduction system
      terminations in the left ventricle and the septum, representing the sites of
      initial activation, on the resulting simulated spatial heart vectors. Three
      differently localized foci of initial activation, each of them represented by one
      model element, were considered: in the central part of the left septal surface,
      posteriorly at about one third of the distance from the apex to the base, and in
      the upper part of the anterior free wall. During the model experiments, the
      positions of the initial activation were shifted +/- 5 model units (ca 5 mm) in
      the vertical and lateral direction either separately or in different mutual
      combinations. Small variations of the initial activation site in the basal parts
      of the left ventricle led to significantly smaller changes of the
      vectorcardiographic loop than variations of the same extent with the initial
      activation site located more apically.

PMID- 1393653
TI  - [Changes in the parameters of respiratory mechanics after the aspiration reflex
      and asphyxia].
AB  - Parameters of respiration mechanics (dynamic compliance--Cdyn and total lung
      resistance--RL), ventilation, blood gases, and right-to-left pulmonary shunts
      were studied after aspiration reflex in experiments on 29 anesthetized cats.
      Attacks of aspiration reflex were induced without asphyxia (8 cats) and during
      two-minute asphyxia (9 cats). The control group consisted of 12 animals. A series
      of aspiration reflex attacks resulted in short-term improvement of the parameters
      of respiration mechanics with an increase in Cdyn and reduction of RL. A
      simultaneous elevation of PaO2 and a decrease of PaCO2 were recorded. In
      combination with asphyxia (hypoxemia and hyperkapnia), the aspiration reflex
      induced a reversed reaction, i.e. decreased Cdyn lasting till the end of
      experiment (3 hours) and an increase of functional alveolar right-to-left shunts.
      The results indicate that in cats impairment of respiration mechanics parameters
      is brought on only when deep inspiration is combined with asphyxia.

PMID- 1393654
TI  - [Orthostatic adaptation of blood pressure and pulse rate in children].
AB  - Reactivity of blood pressure (BP) and heart rate (HR) to active orthostasis was
      studied in 1540 children aged 3-7 years. After changing the position from supine
      to sitting all cardiovascular parameters studied increased significantly. The
      recorded mean increases were as follows: systolic BP-3-7 Torr, diastolic BP-2
      Torr, HR-5-7 beats min-1, pulse pressure 3-6 Torr, mean BP-2-3 Torr. The change
      to erect position induced a further increase. The reactive increments were in
      negative correlation with the initial values (r = -0.3, p < 0.001) in both sexes.
      The incidence of responses with a higher amplitude was significantly higher in
      children from the lower quartiles of supinal BP distribution. The incidence of
      reactive BP drop increased gradually from 7 to 14% of cases.

PMID- 1393655
TI  - [Computer analysis of muscle reflex responses to electric stimulation of
      peripheral nerves].
AB  - A computer program is described which allows analysis of reflex muscle responses
      to electric stimulation of peripheral nerves. Basically, the program is derived
      from an older methodic approach, yet the process of evaluating the obtained means
      of reflex muscle responses is in this computer assisted procedure simpler and of
      a higher quality. The proposed improvement of the original methodic approach
      provides an important advantage for clinical practice in significantly speeding
      up the investigation and evaluation of reflex muscle responses on using
      financially accessible computer technique of Czechoslovak make. The paper points
      out the possibility of using the program also for analysis of other biological
      signals and of adjusting it for more efficient types of personal computers.

PMID- 1393656
TI  - [The effect of head position and functional status of the cervical spine on body
      sway in the upright posture].
AB  - In 30 subjects (16 men and 14 women) stabilometry was used to investigate the
      stability of posture with closed eyes and different positions of the head
      (backward, forward, right and left turn). Cervical spine mobility of the subjects
      studied was determined by vertebrogenic examination. The maximum backward
      extension of the head was found to reduce most markedly posture stability.
      Correlation analysis revealed a relationship between the functional state of the
      cervical spine and the degree of posture stability impairment induced by backward
      extension of the head, with the impairment being more pronounced in the forward
      backward direction. The obtained results show that changes in the quality of
      proprioceptive information from the cervical spine region are also involved in
      determining the stability level of upright posture. The findings imply that
      posture with backward extension of the head can be used as a loading test for
      detecting ataxia of cervical origin.

PMID- 1393657
TI  - [Protective effect of 7-oxo-prostacyclin on myocardial calcium overload in the
      isolated rat heart].
AB  - The protective effect of a stable derivative of prostacyclin (7-oxo PGI2) was
      studied on the model of calcium overload (Ca2+ paradox) 48 h after i.m.
      administration of the drug in the dose of 50 micrograms/kg. In the isolated rat
      heart perfused at 37 degrees C and a constant perfusion pressure of 75 Torr
      (Langendorff preparation) Ca2+ paradox was induced by 3 min perfusion with
      calcium-free Krebs-Henseleit solution and a subsequent 10 min perfusion with a
      normal calcium-containing solution. The late protective effect of 7-oxo PGI2 was
      manifested by improved recovery of heart function (increase of contractility by
      50%) and by better preservation of the content of macroergic phosphates (70%
      sigma ADN) during the Ca2+ repletion phase and of myocardial ultrastructure
      (sarcolemma) already during the Ca2+ depletion phase. The protective effect of 7
      oxo PGI2 can be accounted for by stimulation of Na, K-ATPase activity, otherwise
      decreased during calcium depletion phase, and by the consequent prevention of
      alterations in sodium and calcium homeostasis. (Tab. 1, Fig. 4, Ref. 41.)

PMID- 1393658
TI  - [The effect of postural changes on respiration and blood pressure in premature
      neonates].
AB  - Changes in respiratory rate, heart rate, and blood pressure in supine,
      orthostatic (45 degrees), and prone position were studied in 23 premature
      neonates of mean gestational age 34.5 weeks (30-36), mean birth weight 2100 g
      (1540-2480) and mean postnatal age 52 hours (12-72). The individual positions of
      the newborn were changed in 5-minute intervals. In the orthostatic position, the
      respiratory rate decreased, yet heart rate and blood pressure did not change. In
      pronation, respiration became more regular. In the preceding supine position, the
      coefficient of variation of the duration of respiratory cycles was 28.2 +/- 3.5%,
      while in the 1st minute of pronation it was 15.9 +/- 2.4% and in the 5th minute
      14.3 +/- 1.9% (p < 0.001). In the 5th minute of pronation systemic blood pressure
      was increased. (Tab. 1, Fig. 4, Ref. 20).

PMID- 1393659
TI  - [Molecular basis of regulation of contraction of skeletal muscle cells and the
      role of calcium. Mathematical modeling].
AB  - The review summarizes recent knowledge concerning regulatory mechanisms of
      skeletal muscle cell contraction. Calcium ions are the essential mediator of
      these processes. Their primary function is signal transmission from the
      sarcoplasmic reticulum to contractile proteins. A large variety of methods is
      available for the investigation of such complex molecular processes, ranging from
      physiological through biochemical and morphological to biophysical and
      mathematical approaches. Mathematical modelling is assessed comprehensively in
      the last part of the review. (Fig. 3, Ref. 58.)

PMID- 1393660
TI  - [The effect of carnitine on the early phase of liver regeneration after partial
      hepatectomy in rats with experimental diabetes].
AB  - The effect of intraperitoneally administered carnitine (10 or 100 mg/kg) on the
      early stage of liver regeneration after two-third hepatectomy was studied in rats
      with experimentally induced alloxan diabetes (60 mg/kg IV). The level of
      regeneration was assessed mainly on the basis of DNA synthesis in the liver.
      Untreated diabetic rats exhibited significantly lower values of DNA synthesis
      determined 24 hours after hepatectomy. Administration of carnitine resulted in a
      significant increase in DNA synthesis over the given time interval. The
      stimulatory effect of carnitine in diabetic rats was confirmed also by the
      recorded values of serum lipids, particularly by the decreased concentration of
      triacylglycerols and the increased concentration of HDL-cholesterol, as
      determined in carnitine treated diabetic rats 24 hours following partial
      hepatectomy. (Tab. 2, Fig. 3, Ref. 34.)

PMID- 1393661
TI  - [Long-term results in patients with stereotaxic surgery for psychopathologic
      disorders].
AB  - Long-term results (5-20 years) recorded in 304 patients operated on
      stereotactically for psychopathologic disorders are presented. The largest group
      of 260 surgically treated subjects represented aggressive patients. This group
      consisted of 150 patients with mental retardation, 70 with epilepsy, 20 with
      schizophrenia, and 20 patients with sexual deviations. Amygdalectomy for patients
      with normal intellect and posterior hypothalamotomy for those with reduced
      intellect proved to be the most effective procedure. Symmetrical operations were
      also effective. In some cases a combination of two target was necessary. In
      epileptics with aggressivity the combination of amygdalectomy and hippocampectomy
      yielded the best results. In aggressivity with sexual deviations anterior
      hypothalamotomy was the most effective operation. Favorable results in
      aggressivity therapy were recorded in 60% of patients. In patients with criminal
      sexual deviations, in drug addicts, and in alcoholics, anterior hypothalamotomy
      was found to be most effective, with favorable results in 50% of patients. In
      patients with depression, thalamotomy or stimulation of the limbic regions of the
      thalamus decreased the depression, with favorable results recorded in 66% of
      patients. The results of the surgically treated patients show that target
      oriented stereotactic operations remove psychopathologic symptoms, improve the
      effectiveness of psychoactive drugs and the social adaptability of patients.
      (Ref. 15.)

PMID- 1393662
TI  - [Embolization of the pulmonary artery bed: hemodynamic and respiratory changes].
AB  - Hemodynamic and respiratory changes were studied during embolization of the
      pulmonary arterial bed in 20 rabbits after pentobarbital anesthesia. Air was
      insufflated into the auricular vein in the amount necessary to induce circulatory
      and respiratory changes. Circulatory changes were manifested by decreased
      arterial blood pressure, increased blood pressure in the right atrium, and aortal
      and pulmonary blood flow reduced to zero. The respiratory rate was diminished. A
      series of deep inspirations was followed by apnoe and death of the animal. (Fig.
      5, Ref. 9.)

PMID- 1393663
TI  - [The HLA complex in 1991].
AB  - In November 1990 the Nomenclature Committee of the WHO updated the designation of
      loci, alleles, and antigens of the HLA complex. Their complete list is presented
      in our review, along with current knowledge on the complexity of the HLA-D
      region. Finally, the paper deals with the tertiary structure of HLA antigens
      discovered in 1987, which has enabled us to understand the biological
      significance of the HLA complex. (Fig. 5, Tab. 5, Ref. 15.)

PMID- 1393664
TI  - [The physician and the personal computer].
AB  - Nowadays the personal computer is being used in a broad range of activities. Its
      user is also its operator, directly controlling the process. The paper describes
      both hardware and software, the structure of the PC, its input and output
      equipment, basic principles of work with a PC, programs and programming, as well
      as computer languages. A classification of personal computers is presented and
      the most frequently used types are assessed. (Fig. 5, Ref. 15., Tab. 1)

PMID- 1393665
TI  - Fear of humans and its relationships with productivity in laying hens at
      commercial farms.
AB  - 1. The relationship between the behavioural responses of laying hens to humans
      and productivity was determined at 16 commercial sheds from 14 farms. 2. A number
      of behaviour variables were moderately to highly correlated with production
      variables; for example, the proportion of birds that moved away from an
      approaching experimenter in an unfamiliar environment ('shute test') was
      negatively correlated with peak hen day production, (PKHDP). 3. Behavioural
      responses to humans accounted for between 23 and 63% of the variation in a number
      of production variables, including PKHDP and the duration of a high level of
      production. 4. Inclusion of farm factor variables increased the amount of
      variation accounted for by the behaviour variables. For example, adding the
      variable 'time/day spent in the shed by stockpeople' to the behaviour variables
      'the proportion of birds that moved away from an approaching human' in the shute
      test and 'the number of times birds in cages adopted an erect posture' in
      response to an approaching human increased the variation accounted for in PKHDP
      from 53 to 61%. 5. The results suggest that fear of humans may be a factor that
      limits the productivity of commercial laying hens.

PMID- 1393666
TI  - Responses of broiler chickens to high-frequency and low-frequency fluorescent
      light.
AB  - 1. The influence of the flicker frequency on physical activity and energy
      expenditure of broilers was studied using commercially available high-frequency
      (HF) and low-frequency (LF) fluorescent lamps in a 23L:1D lighting schedule. 2.
      Broilers were reared under and adapted to HF. They were alternately subjected to
      HF and LF during measurement of activity and energy expenditure. 3. In comparison
      with HF, LF inhibited activity (number and intensity of movements), but did not
      influence energy expenditure. 4. It was concluded that the 100 Hz flickering of
      low-frequency light is detected by broilers and has measurable behavioural
      effects upon them. 5. The results were discussed in relation to current knowledge
      of human and birds' critical flicker frequency and perception.

PMID- 1393667
TI  - Influence of age and body mass on the heating effect of microwave radiation in
      broilers.
AB  - 1. A total of 648 broilers was used in a factorial combination of 3 ages x 3 body
      masses x 4 microwave treatments to examine the possible interaction between bird
      age and body mass on the heating effect of microwaves. 2. As age or body mass
      increased, the increase in body temperature following exposure to microwaves
      decreased curvilinearly. 3. A significant interaction was evident between age and
      body mass. For the same body mass, microwave radiation exerted a greater heating
      influence at the younger age. 4. A model for the heating effect of microwaves is
      presented which takes into account the influence of both bird age and irradiated
      body mass.

PMID- 1393668
TI  - Effects of temperature on the migration of primordial germ cells in the chick
      embryo.
AB  - 1. Incubating eggs at reduced temperatures leads to a decline in the rate of
      embryonic development. 2. All tissues do not respond equally and the migration of
      primordial germ cells is delayed in time, but occurs at an earlier stage of
      development than for normally incubated eggs. 3. The results are interpreted in
      relation to the integrated development of the gonad.

PMID- 1393670
TI  - Effect of faecal extract on the growth of Salmonella enteritidis in artificially
      contaminated hens' eggs.
AB  - 1. Salmonella enteritidis PT 4 grew in eggs stored at 25 degrees C, but not at 10
      degrees C. 2. The incidence of generalised infection of the egg contents (greater
      than 10(6) salmonellas/ml) was greater in eggs inoculated with cells suspended in
      faecal extract compared to those with cells in Ringer's solution. 3. The removal
      of most of the iron did not decrease the growth-promoting effect of the faecal
      extract.

PMID- 1393669
TI  - Direct and correlated responses to divergent selection for residual food intake
      in Rhode Island Red laying hens.
AB  - 1. Divergent selection was undertaken in a Rhode Island Red population for
      residual food intake, measured in males and females, using mass selection. 2. In
      the absence of a control line, selection response during 14 generations was
      estimated by the within-year divergence between lines. 3. The direct response in
      residual food intake was found to be significant in both sexes, the divergence
      reaching almost three phenotypic standard deviations in each sex. 4. Significant
      correlated responses were obtained for food efficiency; it was improved in the
      low residual food intake line. Shank length, wattle length and rectal and comb
      temperature showed higher values in the high line, suggesting an increased heat
      production or dissipation. Inconsistent changes were observed for other egg
      production traits.

PMID- 1393671
TI  - Techniques for the isolation of salmonellas from eggs.
AB  - 1. When the contents of 4 or more naturally-contaminated intact eggs were
      combined, the isolation rate of Salmonella enteritidis was improved by extending
      incubation at 37 degrees C from 24 to 48 h before sub-culture. 2. The isolation
      rate of salmonellas from raw homogenised whole egg was significantly increased by
      the inclusion of Novobiocin and Cefsulodin in the primary culture media. 3.
      Rappaport Vassiliadis broth was found to be superior to Selenite as a selective
      enrichment medium.

PMID- 1393672
TI  - Influence of age on the febrile response to E. coli and S. typhimurium endotoxins
      in growing pullets.
AB  - 1. The effect of bacterial endotoxin injection was studied in growing pullets of
      different ages. Commercial chicks were divided into 5 groups according to age.
      Bacterial endotoxins (E. coli and S. typhimurium) were injected intravenously and
      rectal temperature was measured over a period of 300 min. 2. The results showed
      no significant effect of age on the febrile response induced by bacterial
      endotoxins, but a slight tendency towards a reduced fever peak was observed with
      increasing age. The response latency also increased with age.

PMID- 1393673
TI  - Use of competitive exclusion to protect newly-hatched chicks against intestinal
      colonisation and invasion by Salmonella enteritidis PT4.
AB  - 1. The recommended dose of a commercial competitive exclusion (CE) product
      (BROILACT) was given orally to newly-hatched broiler chicks to protect them
      against oral challenge by Salmonella enteritidis PT4. 2. In 5 replicate trials,
      half of the birds thus treated and half from untreated control groups were
      examined for salmonellas at 5 d and the other half at 12 d after challenge. 3.
      Caecal contents were examined quantitatively while heart, liver and spleen
      samples were examined qualitatively by enrichment. 4. The treatment effectively
      prevented both colonisation of the caeca and invasion of the other organs by S.
      enteritidis PT4; the average number of salmonellas was less than 10 colony
      forming units (cfu)/g of caecal contents in the treated birds and more than 10
      million cfu/g in the untreated birds. 5. Infection of organs other than the caeca
      was completely prevented by protective treatment, whereas 38% of the untreated
      birds were still infected at the end of the trial.

PMID- 1393674
TI  - Effects of dietary protein concentration on the response of growing chicks to
      methionine.
AB  - 1. Experiments were conducted independently at two stations to measure the
      requirement for methionine in chick diets with crude protein (CP) varying in 8
      steps from 140 to 280 g/kg diet (experiment 1) or from 90 to 300 g/kg (experiment
      2). 2. Protein composition was the same at all protein concentrations within a
      trial. The diet was designed to be first-limiting in methionine and DL-methionine
      was added to provide 5 ratios of methionine to CP at each protein concentration.
      3. Methionine required for maximum growth rate or maximum efficiency of food
      utilisation was estimated at each protein concentration by fitting a quadratic
      regression equation to the relevant data. The requirement was also estimated by
      fitting the Reading model to data for growth rate and methionine intake. 4. In
      both trials and by all three methods of estimation, the methionine requirement
      (g/kg diet) for maximum performance increased as a linear function of dietary CP
      concentration and nearly in direct proportion to CP. 5. It is concluded that
      diets which contain surplus protein, beyond that needed to maximise growth rate
      or food efficiency, need supplementation with methionine beyond that required
      when dietary protein is just adequate. A suitable rule for practical formulation
      is that methionine concentration in chick diets should be not less than 0.025
      times the dietary CP concentration.

PMID- 1393675
TI  - Involvement of food intake in the decreased energy retention associated with
      single deficiencies of lysine and sulphur-containing amino acids in growing
      chicks.
AB  - 1. Growth and energy utilisation were determined in growing chicks fed ad libitum
      on diets deficient either in lysine (5.95 g/kg) or in sulphur-containing amino
      acids (SAA, 3.5 g/kg). Food intake, body weight gain, energy retained as protein
      and as fat, and total energy retention were significantly (P less than 0.05)
      reduced by single deficiencies of either lysine or SAA. 2. Another two
      experiments were conducted to determine if the decreased total energy retentions
      in chicks fed on diets deficient in lysine (experiment 3) or SAA (experiment 4)
      were associated with reduced food intake, by using tube-feeding to control the
      amount and pattern of food consumption. Chicks fed on diets deficient in lysine
      or SAA retained less energy as protein and more energy as fat than the control
      chicks. Neither total energy retention nor heat increment was affected by these
      deficiencies. Total energy retention was proportional to metabolisable energy
      (ME) intake alone. 3. It is concluded that the decreased total energy retentions
      caused by single deficiencies of lysine and SAA were associated with decreased
      food intake.

PMID- 1393676
TI  - Effect of colostomy on the utilisation of dietary nitrogen in the fowl fed on a
      low protein diet.
AB  - 1. The effect of the inhibition of urine back-flow into the colon and caeca by
      colostomy on the utilisation of dietary nitrogen by fowls fed on a low protein
      diet and receiving free or restricted water supply was investigated. 2. Colostomy
      caused an increase in water excretion and a resultant increase in water intake to
      maintain water balance. 3. Colostomy tended to decrease nitrogen balance and
      nitrogen utilisation (N balance/N intake) to negative values, and these decreases
      became significant when water was restricted (P less than 0.05). 4. Excretory
      uric acid, ammonia, urea and total nitrogen were significantly increased after
      colostomy in water-restricted fowls (P less than 0.05), but such significant
      effects were not observed, except for ammonia, in fowls given water ad libitum.
      5. It is concluded that the back-flow of urine into the caeca plays a
      significantly useful role in the utilisation of nitrogen in the fowl fed on a low
      protein diet especially when water intake is restricted.

PMID- 1393677
TI  - Anti-nutritive effect of wheat pentosans in broiler chickens: roles of viscosity
      and gut microflora.
AB  - 1. The mechanism of the anti-nutritive activity of isolated wheat pentosans was
      investigated by examining the roles of digesta viscosity and gut microflora in
      broiler chickens. 2. Wheat pentosans were isolated by alkaline extraction and
      purified by sequential treatment with pancreatin, alpha-amylase and lichenase,
      and high-speed centrifugation. Some of the pentosans were depolymerised using a
      beta-xylanase, which reduced the relative viscosity of the polysaccharides 4
      fold. 3. Inclusion of 35 g alkali-extractable pentosans (containing 854 g
      arabinoxylans/kg DM) per kg diet significantly (P less than 0.05) depressed
      broiler performance and the viscosity of the digesta of these birds was
      significantly (P less than 0.05) higher than that of controls. Addition of the
      same amount of depolymerised pentosans had no significant effect on bird
      performance and had less effect on digesta viscosity. 4. Supplementation of the
      diet containing wheat pentosans (30 g/kg) with procaine penicillin (150 mg/kg)
      did not improve bird performance. 4. It is concluded that the wheat pentosans
      elicit their anti-nutritive activity predominantly through increasing the
      viscosity of digesta.

PMID- 1393678
TI  - Production, hatchability and fertility of eggs from breeding Japanese quail
      (Coturnix coturnix japonica) fed diets containing furazolidone.
AB  - 1. Breeding Japanese quail were allocated to 8 groups, each group consisting of
      20 females and males. The birds were fed one of 4 diets for up to 33 d: a control
      diet or a diet containing 200 mg/kg, 400 mg/kg or 1000 mg/kg furazolidone.
      Subsequently, quails were fed a furazolidone-free diet for up to 21 d. Egg
      production, quality, hatchability and fertility of the groups were measured. 2.
      Significant reduction in egg production occurred in birds fed 400 mg/kg and 1000
      mg/kg furazolidone, the effect being more pronounced at the higher concentration.
      3. Hatchability was reduced significantly for all groups of birds fed
      furazolidone and this effect was both dose and time dependent. The reduction in
      hatchability was attributable to an increase in infertile eggs rather than an
      increase in embryonic mortality. 4. Egg quality was affected, with more small
      eggs being produced by birds fed 1000 mg/kg furazolidone. 5. After removal of the
      experimental diets egg production of the affected groups returned to control
      values. Hatchability and fertility of affected groups also returned toward
      control values, but had generally not attained these values 21 d after the
      cessation of the experimental diets. 6. It was concluded that standard
      recommendations for the therapeutic dosage of poultry with furazolidone may not
      be appropriate for breeding Japanese quail.

PMID- 1393679
TI  - Induction of ovarian growth and ovulation by administration of a chicken
      gonadotrophin preparation to Japanese quail kept under a short-day regimen.
AB  - 1. Chronic administration of a glycoprotein fraction from chicken pituitary using
      an ALZET osmotic pump at 12.5 micrograms/h for 2 weeks induced growth of ovarian
      follicles to a mature size in the ovary and deposition of yolk in sexually
      immature 6-week-old Japanese quail females which were kept under 8L:16D short-day
      conditions. However, no ovulation was induced in these birds. 2. Injection of 500
      micrograms of the glycoprotein into other immature short-day females was
      performed following the above chronic administration, 12 or 14 and 15 d after
      implantation of the osmotic pump. About 24 h after injection, 3 of 14 females
      laid one or two eggs. Ovulation was confirmed in 4 females by autopsy. A total of
      5 of 14 females ovulated 6 eggs, and significant development of the oviduct and
      the cloacal opening were observed in all of the treated females. 3. Thus,
      complete ovarian function could be induced in sexually immature female Japanese
      quail by administration of avian gonadotrophin using a combination of an osmotic
      pump and an injection.

PMID- 1393680
TI  - Whole blood and plasma viscosity values in normal and ascitic broiler chickens.
AB  - 1. Whole blood and plasma viscosity values in normal and ascitic broiler chickens
      were measured. 2. The mean blood viscosity value in ascitic broilers was greater
      than that of the controls. There was a small but significant difference in the
      opposite direction between plasma viscosity values of the respective groups of
      birds. 3. Although the haematocrit and arterial pressure index values in the
      ascitic birds were raised, there was a fall in the concentration of total plasma
      protein. 4. The data suggest that the raised viscosity in the ascitic birds was
      caused by a polycythemia and not by any influence of plasma protein. 5. The
      cumulative effect of these factors, such as raised blood viscosity values and
      larger deformed red cells flowing through constricted lung arterioles, may
      contribute to the pulmonary hypertension and ascites seen in some young
      commercial broilers.

PMID- 1393681
TI  - Association of (3H) DNA with fowl spermatozoa and their in vitro fertilisation of
      hamster ova.
AB  - 1. Fowl spermatozoa incubated with DNA were used for the fertilisation of zona
      free hamster oocytes. 2. Two categories of spermatozoa were detected: those which
      were not labelled and those which showed a very high degree of labelling (19 +/-
      2% of the whole population). 3. In the hamster oocytes exposed to treated
      spermatozoa the labelled sperm heads were identified.

PMID- 1393682
TI  - Energy utilisation of medium chain triglyceride in comparison with long chain
      triglyceride in growing chicks.
AB  - 1. To evaluate the relative efficiency of energy utilisation of medium chain
      triglyceride (MCT) compared to long chain triglyceride (LCT), Single Comb White
      Leghorn 7-d-old male chicks were allocated into 4 experimental groups and one
      control of 5 birds per group. The chicks in the control group (Group 1) were
      given 5 g basal diet each day for 10 d. The birds in groups 2 and 3 received 5 g
      basal diet/d supplemented with MCT to provide 33.5 kJ GE/d and 67.0 kJ GE/d, and
      those in groups 4 and 5 were supplemented with LCT at 31.9 kJ GE/d and 63.8 kJ
      GE/d, respectively. Energy retained as protein and fat, and total energy
      retentions were measured. 2. No significant differences were found in energy
      retention as protein between the four energy supplemented groups but significant
      differences in fat and total energy retentions were found between the different
      dietary energy contents but not between energy source. Net energy of MCT for
      production was calculated as 16.0 kJ/g which corresponds to about 74% of that of
      LCT (22.8 kJ/g).

PMID- 1393683
TI  - Further studies on the inheritance of the marbled chickdown phenotype of the
      domestic fowl.
AB  - 1. An investigation was conducted among the progeny from crosses between Birchen
      Modern Game and Silver Sebright bantams into the inheritance of the marbled
      chickdown phenotype of the latter. 2. The marbled chickdown phenotype has been
      shown to depend upon homozygocity of both the birchen allele ER at the E-locus
      and the eumelanin restrictor gene Db. However, all stock used to establish this
      result were also homozygous for the linked eumelanin intensifier melanotic Ml and
      the pattern gene Pg, therefore yielding no information on the roles of Ml or Pg
      in the marbled chickdown phenotype. 3. Examination of the F2 generation both of
      chickdown and of adult plumage demonstrated the marbled chickdown to be
      homozygous ER (Db-Pg) with Ml dosage having an effect on adult plumage.

PMID- 1393684
TI  - Patient-controlled analgesia for cancer pain: a long-term study of inpatient and
      outpatient use.
AB  - The safety and efficacy of patient-controlled analgesia for the long-term control
      of cancer pain was tested prospectively. Respiratory rates, mental status, and
      pain relief were recorded at baseline and compared with those during the study
      period. Patients had a lower analgesic demand (i.e., self-administered less
      morphine during the nighttime); specifically, dosing declined 48% from the
      daytime level. Respiratory rates did not change appreciably during the study and
      no cases of significant respiratory depression were encountered. Patients self
      administered sufficient morphine to produce adequate but not complete pain relief
      in almost all trials. Pain relief was safely achieved by both intravenous and
      subcutaneous routes of administration in both the inpatient and outpatient
      settings. Mean 24-h morphine use stayed relatively constant even for patients
      receiving more than 2 weeks of treatment. In conclusion, patient-controlled
      analgesia is effective and safe therapy for the long-term control of severe
      cancer pain.

PMID- 1393686
TI  - Simultaneous radiotherapy and chemotherapy with carboplatin in inoperable
      squamous cell carcinoma of the head and neck: a phase II study.
AB  - Fifty-six untreated patients with inoperable squamous cell carcinoma of the head
      and neck were treated with carboplatin 70 mg/m2 i.v. daily on days 1-5 and 29-33
      in combination with simultaneous conventional radiation up to a target volume
      dose of 50 Gy. Depending on tumor response and upon recommendation of surgeons,
      21 of 56 patients underwent surgery after a radiation dose of 50 Gy and two
      courses of carboplatin. Patients who showed pCR after surgery received no further
      radiotherapy. In all other patients radiotherapy was continued using a shrinking
      field technique up to a target absorbed dose of 70-74 Gy. Combined modality
      induced 66% complete remission (CR) and an overall response rate of 98%. After
      completion of the whole treatment program (combined modality +/- surgery) 53
      (94%) of the 56 patients were disease free. The median survival for all patients
      is 25+ months and the percentage of two-year survivors is 53%. Myelosuppression
      was the most frequent toxicity, but rarely was severe; leukopenia and
      thrombocytopenia of WHO grade 3 occurred in 21% of the patients. No other
      toxicities above WHO grade 2 occurred. Nephrotoxicity, neurotoxicity and
      ototoxicity were not seen. The addition of carboplatin did not increase the rate
      of surgical complication over that expected for preoperative radiotherapy. Two
      patients died of pulmonary embolism after surgery. Combined modality with
      carboplatin and simultaneous radiation is a highly active and well-tolerated
      regimen for untreated patients with inoperable squamous cell carcinoma of the
      head and neck.

PMID- 1393685
TI  - Nonspecific immunostimulation with low doses of cyclophosphamide (LDCY),
      thymostimulin, and Echinacea purpurea extracts (echinacin) in patients with far
      advanced colorectal cancers: preliminary results.
AB  - Outpatients (n = 15) with metastasizing far advanced colorectal cancers received
      immunotherapy consisting of low-dose cyclophosphamide (LDCY) 300 mg/m2 every 28
      days i.v., thymostimulin 30 mg/m2, days 3-10 after low-dose cyclophosphamide i.m.
      once daily, then twice a week, and echinacin 60 mg/m2 together with thymostimulin
      i.m. All patients had had previous surgery and/or chemotherapy and had
      progressive disease upon entering the study. Two months after onset of therapy a
      partial tumor regression was documented in one and a stable disease in 6 other
      patients by abdominal ultrasonography, decrease of the tumor markers
      carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, and/or chest roentgenography,
      which may also be attributed to the natural course of disease. Mean survival time
      was 4 months, 2 patients survived for more than 8 months. Immunotherapy was well
      tolerated by all patients without side effects.

PMID- 1393688
TI  - The role of surgery in early stage glottic carcinoma.

PMID- 1393687
TI  - Immunotherapy with sensitized lymphocytes.

PMID- 1393691
TI  - Indications for breast conservation in early stage breast cancer.
AB  - Breast conservation, utilizing limited excisional breast surgery and axillary
      lymphadenectomy followed by radiation therapy can achieve excellent
      local/regional control and survival in many breast cancer patients. With average
      sized tumors, where larger volume resections are performed the results can equal
      that of the modified radical mastectomy. However, smaller tumors do very well
      with breast removal so it is a challenge to demonstrate that the long-term
      results of breast conservation in earlier stage disease are equivalent to
      mastectomy. Small or occult tumors do not always indicate localized disease and
      suitability for breast conservation depends on a combination of factors: tumor
      size and ratio of tumor to breast volume, cell type, location of tumor, obtaining
      clear margins, the mammographic picture, multicentricity, and the probability of
      axillary lymph node involvement. It is important to select patients for
      conservation where an equivalent survival can be expected. Recurrence in the
      radiated breast usually is diagnosed and treated at a more advanced stage than
      the disease which was initially treated conservatively. It is difficult to manage
      and carries a poorer prognosis.

PMID- 1393689
TI  - Molecular biology in the diagnosis and prognosis of solid and lymphoid tumors.
AB  - The application of molecular biology to the study of human malignancies has led
      to tremendous gains in our understanding of their pathogenesis. Although their
      practical applications are still somewhat limited at this point, the use of
      molecular diagnostic tools is likely to grow at a very rapid rate as newer and
      more accurate prognostic markers are identified. The availability of reliable
      prognostic markers should allow earlier intervention in patients with aggressive
      disease but exhibiting only limited extent of disease at the time of initial
      diagnosis. Early intervention in such cases could realistically increase the
      probability of cure, since highly aggressive tumor cells are more likely to be
      eliminated by early institution of cytotoxic chemotherapy (4). The p53 tumor
      suppressor gene clearly represents the most promising potential prognostic marker
      at present, because of both the multiple phenotypic alterations caused by
      different p53 mutations and the high frequency of p53 mutations which have been
      observed in a variety of human cancers. Other prognostic markers related to
      oncogenes and tumor suppressor genes are almost certain to follow. Validation of
      new prognostic markers requires a knowledge of both histopathologic diagnostic
      criteria as well as the consequences for the patient of each diagnosis. There is
      bound to be some "shake-out" in the field of molecular diagnostics just as there
      was with other recently introduced techniques such as immunohistochemistry and
      flow cytometry which were found to provide additional useful information for some
      tumors and not for others. Since the clinical-pathologic studies needed for
      verification of putative prognostic markers require relatively long periods of
      follow up, progress in this area will almost certainly lag behind the ability of
      molecular biologists to identify new and potentially useful prognostic markers.
      Our collective ability to reap tangible gains in the clinical arena from our
      heavy investments in molecular biology and biotechnology depends to a large
      extent on open channels of communication between clinical and basic scientists.
      As our ever-increasing insights into oncogenic processes spawn new diagnostic and
      prognostic markers, our priorities should remain focused on those areas which are
      inadequately addressed by current methods, and we should avoid the technological
      trap of devising redundant solutions which increase the expense, but not the
      efficiency of patient care.

PMID- 1393690
TI  - The polymerase chain reaction: its use in the molecular characterization and
      diagnosis of cancers.

PMID- 1393692
TI  - The role of axillary dissection in early stage breast cancer.

PMID- 1393693
TI  - Patient selection for treatment with conservative surgery and radiation therapy.
AB  - There is now general agreement that treatment with conservative surgery and
      radiation therapy yields survival equal to mastectomy with the advantage of organ
      preservation for properly selected patients. When competently performed, such
      treatment gives highly satisfactory cosmetic results and acceptably low rates of
      local tumor recurrence. However, there remain numerous controversies concerning
      patient selection for this treatment option. The factors involved in patient
      selection may be grouped into three categories: patient factors; clinical
      factors; and pathologic factors. This article reviews their use. Because breast
      cancer has a long natural history, long follow up of patients is required for
      ultimate proof of the relative merits of different selection or treatment
      policies. However, due to the increasing numbers of patients being treated with
      conservative surgery and radiotherapy, it appears likely that many of these
      questions will be answered within the next decade.

PMID- 1393694
TI  - Are DNA flow cytometry measurements providing useful information in the
      management of the node-negative breast cancer patient?
AB  - The appropriate management of the breast cancer patient with early stage disease
      is a controversial, frustrating issue. If laboratory tests could accurately
      predict tumor behavior, however, the clinician and patient would be greatly aided
      in their treatment decisions. Although imperfect, there are several new and
      significant factors that can be used to predict patient prognosis; the most
      promising and well studied of these factors are DNA flow cytometry measurements.
      There are at least two estimates of tumor aggressiveness that we can obtain from
      DNA flow cytometry: one is an estimate of the tumor DNA content or ploidy and the
      other is an estimate of the tumor proliferative capacity. These measurements have
      their greatest clinical impact in the node negative patient predicting for
      relapse-free survival and overall survival. Estimates of proliferative capacity
      are independent predictors of patient prognosis. Estimates of DNA content are at
      times controversial and yet still are helpful in distinguishing prognostic
      subgroups of proliferative activity and may have additional clinical relevance.
      This discussion will summarize the data obtained from DNA flow cytometry
      measurements supporting their use as clinically important markers of prognosis in
      the node-negative patient.

PMID- 1393696
TI  - Best papers on lung cancer.

PMID- 1393695
TI  - Best papers on colon cancer.

PMID- 1393697
TI  - New directions for radiologic research.

PMID- 1393698
TI  - The radiologic spectrum of abnormalities of the foot in diabetic patients.
AB  - Radiologically visible lesions in the feet of patients with long-standing
      diabetes mellitus are common and varied. They include osteoporosis,
      osteosclerosis, osteolysis, juxta-articular defects of the cortical bone,
      ischemic bone necrosis, new bone formation, spontaneous fracture and subluxation,
      and neuropathic arthropathy. These manifestations result from diabetic angiopathy
      and neuropathy and usually are complicated by infection. In this review the
      author describes these protean radiologic features in light of their pathogenesis
      and discusses the diagnostic problems encountered.

PMID- 1393699
TI  - [Cancer of the breast in radiology].
AB  - In this extensive review the author discusses the incidence of breast cancer,
      screening methods, the theoretic radiation risk, the mammographic signs of
      suspicious lesions and the value of ultrasonography and stereotactic fine-needle
      biopsy. The emphasis is on the close relation between radiology, the physical
      examination, surgery and pathological studies. Up-to-date information about
      controversial topics is provided, and a therapeutic scheme is suggested.

PMID- 1393700
TI  - Granulomatous orbital lesions: computed tomographic features.
AB  - Orbital lesions exhibiting granulomatous inflammation represent a heterogeneous
      group of diseases characterized by infiltration with epithelioid cells. The
      authors retrospectively reviewed the orbital computed tomography (CT) scans of 39
      patients who had biopsy-proven lesions with granulomatous inflammation and found
      that diagnosis on the basis of CT was possible in only a few patients, those with
      a lesion of characteristic location and attenuation (such as a dermoid cyst) or
      characteristic distribution (such as bilateral enlargement of the lacrimal gland
      occurring in orbital sarcoidosis). In patients with multicompartmental disease
      exhibiting bone and extraorbital involvement the site of origin of the mass, the
      pattern of bone involvement and the clinical findings helped in classifying the
      cause of the lesion as Wegener's granulomatosis, a foreign body or mucormycosis.
      CT was crucial in determining the intraorbital and extraorbital extent of the
      lesion before excision or biopsy.

PMID- 1393701
TI  - Ultrasonography-directed native renal biopsy: comparison of an automated biopsy
      device with a needle system.
AB  - The authors compared the performance of an automated biopsy device with a large
      bore cutting needle system in ultrasonography-guided native renal biopsy. They
      retrospectively analysed 52 biopsy specimens from 50 adults with diffuse renal
      parenchymal disease. Twenty-six consecutive biopsy samples had been obtained
      manually with a 14-gauge needle (Tru-Cut, Travenol Laboratories, Deerfield,
      Ill.); a second set of 26 samples had been obtained with a biopsy gun (Bard
      Biopty, Radiplast, Uppsala, Sweden) fitted with a 14-gauge needle of similar
      design. The systems were compared in terms of the specimens obtained (the
      adequacy and the quality of tissue, the number of intact glomeruli and the
      presence of artifacts) and the incidence of biopsy-related complications. Biopsy
      specimens obtained with the biopsy gun were judged qualitatively as well as
      quantitatively superior; they contained an average of 17.6 intact glomeruli,
      whereas only 11.5 intact glomeruli were retrieved with the needle system.
      Although the incidence of minor complications was lower after biopsy with the
      automated gun than after use of the needle system (8% and 15% respectively), two
      major complications were observed after gun biopsy and none after needle biopsy.
      The results reported here indicate that for native renal biopsy the Biopty gun
      delivers a higher-quality tissue core with a lower frequency of minor
      complications, but not of major complications, than the Tru-Cut needle system.

PMID- 1393702
TI  - Spondylometaphyseal dysplasia, Sutcliffe type: a rediscovered entity.
AB  - The authors describe two children with spondylometaphyseal dysplasia, Sutcliffe
      type. This easily recognizable form of bone dysplasia is characterized by coxa
      vara, minimal metaphyseal changes, oval vertebral bodies and metaphyseal corner
      fractures later in life. It is probably the most common type of
      spondylometaphyseal dysplasia. Early diagnosis is important for proper
      management.

PMID- 1393703
TI  - Are there predictors for future academic radiologists? A Canadian survey.
AB  - In 1990 the authors surveyed all members of the Canadian Association of
      Radiologists and all graduates of the radiology residency program at the
      University of British Columbia in the previous 10 years. They compared
      radiologists with and those without a university affiliation to determine the
      influences on career choice. The factors considered included teaching, research
      and publication experience, as well as educational background. Most respondents
      had decided on a career path during the second half of the residency or later.
      The authors found certain predictors and influences associated with a greater
      probability that a radiologist would pursue an academic career. For example,
      academic radiologists were more likely to have performed research, published and
      presented the results of their research activities, and taught before undertaking
      the residency program in radiology than their counterparts who were not
      affiliated with a university or a residency program. However, class standing in
      medical school and prior educational experience were similar for academic and
      nonacademic radiologists. The influences most often cited as leading toward an
      academic career were a desire to teach, the inspiration of a role model and an
      interest in research. Job satisfaction was higher among nonacademic radiologists,
      as indicated by the number that would consider a career change. Most of the
      respondents disapproved of a special residency curriculum for academic
      radiologists.

PMID- 1393705
TI  - Benign biliary cystadenoma.
AB  - Biliary cystadenomas and cystadenocarcinomas are rare. They arise in the liver
      or, less frequently, from the bile ducts. The characteristic appearance of these
      lesions in computed tomography and ultrasonography scans, as observed in a 26
      year-old woman, is described. The features are similar to those of hydatid
      disease, and without travel history and the results of stool cultures and
      serologic tests differentiation may be impossible. Other considerations in the
      differential diagnosis are also discussed. Surgery is always indicated, because
      benign and malignant tumours in this area cannot be differentiated
      radiologically.

PMID- 1393704
TI  - Pulmonary arterial embolism secondary to hydatid cyst of the liver.
AB  - Complications may develop after spontaneous or traumatic rupture of hydatid
      cysts. A rare complication is pulmonary embolism after rupture of such a cyst
      into the venous system. The authors present the pulmonary radiologic findings for
      a patient whose pulmonary complaints gradually increased after surgical removal
      of a hepatic hydatid cyst.

PMID- 1393706
TI  - Large renal arteriovenous malformation: scintigraphic evaluation and therapeutic
      embolization.
AB  - The authors describe a patient with a rare type of renal arteriovenous
      malformation, which was successfully treated by therapeutic coil embolization.
      Embolization did not destroy healthy renal tissue, as was shown by the Cerino
      technique, which measures the glomerular filtration rate of each kidney by image
      processing for standard renograms obtained after administration of diethylene
      triaminepenta-acetic acid labelled with technetium 99m.

PMID- 1393707
TI  - Idiopathic dilatation of the thoracic venous system.
AB  - Isolated venous aneurysm is a rarely reported cause of a mediastinal mass. The
      authors describe a patient who demonstrated aneurysmal dilatation of the superior
      vena cava, the left innominate vein, the azygos and the hemiazygos veins and the
      left inferior pulmonary vein after blunt chest trauma. This case emphasizes the
      value of computed tomography in the diagnosis of this complex, presumably
      congenital entity.

PMID- 1393708
TI  - Residents' corner. Answer to case of the month #15. Diagnosis. Congenital cystic
      adenomatoid malformation of the lung (type I).

PMID- 1393709
TI  - Child maltreatment as a community problem.
AB  - This report reviews research on the community dimensions of child maltreatment
      and presents a study conducted in the United States designed to illuminate
      further the importance of social environmental effects on family functioning. The
      study involves 77 community areas within the Chicago, Illinois, metropolitan
      area. Child maltreatment rates are related to indicators of socioeconomic and
      demographic well being for these neighborhoods and for the subunits within them.
      The results reveal a strong influence of socioeconomic and demographic factors on
      child maltreatment rates. A further analysis involves selecting pairs of
      neighborhoods for additional study. In this phase of the research the character
      of socioeconomically similar areas with contrasting patterns of child
      maltreatment is revealed. The high-risk areas are characterized by social
      disorganization and lack of social coherence, in contrast to the low-risk areas
      which evidence a stronger social fabric. These effects extend to differences in
      child abuse fatalities.

PMID- 1393710
TI  - Protecting seriously mistreated children: time delays in a court sample.
AB  - The study examined the progress through the child protective system of a sample
      of 206 severely abused and/or neglected children brought before the Boston
      Juvenile Court (BJC) on Care and Protection (C & P) petitions. Overall, children
      were in the system an average of 5 years from the filing of the first official
      report of mistreatment to the resolution of their cases. The families had been
      known to the state child protective service agency for an average of more than
      2.5 years before the current court involvement. Once arraigned in juvenile court
      on the C & P, the average case took almost 1.5 years to reach a disposition.
      After disposition, children permanently removed from parental custody required,
      on average, an additional year and a half in Probate Court to reach a permanent
      placement. Of the more than twenty variables examined, including severity of
      mistreatment, protective service history, and parental mental illness, no
      meaningful pattern emerged which could predict delays. Our findings characterize
      the delays experienced by many abused and neglected children, and highlight the
      necessity of closer monitoring of the progress of cases through the protective
      and court systems.

PMID- 1393711
TI  - Parental substance abuse and the nature of child maltreatment.
AB  - The authors reviewed 190 randomly selected records from the case load of a large
      juvenile court. These records involved cases in which the state took legal
      custody of the children following a finding of significant child maltreatment,
      based on a "clear and convincing" standard of evidence. Sixty-seven percent
      (127/190) of these cases involved parents who were classified as substance
      abusers. The results of this study revealed specific associations between (a)
      alcohol abuse and physical maltreatment and (b) cocaine abuse and sexual
      maltreatment. Logistic analyses, testing for the effects of polysubstance abuse,
      revealed that additional forms of substance abuse failed to add significantly to
      the effects of alcohol in predicting physical maltreatment or cocaine in
      predicting sexual maltreatment.

PMID- 1393712
TI  - What happens after the care and protection petition? Reabuse in a court sample.
AB  - Of 206 cases of serious child mistreatment brought before a metropolitan juvenile
      court on Care and Protection Petitions (C & P), 63 (31%) were dismissed
      (returning the child to the parent(s]. During a 2-year follow-up period, 18 (29%)
      of these dismissed cases had substantiated reports of further mistreatment, and
      10 (16%) subsequently returned to court on another C & P. Families that had
      previously been to court for a C & P, and those in which the parent was diagnosed
      psychotic or character disordered, were significantly more likely to return to
      court. In addition, we were surprised to find that 8 (6%) of the 130 children
      ordered permanently removed from parental custody also returned to court. This
      study documents the continuing mistreatment of children, even after the state's
      most serious interventions. The study also highlights the necessity of
      incorporating clinical research in the form of ongoing follow-up of individual
      cases into the court process, and suggests that it may be possible to identify
      cases with a very high probability of reinjury and return to court.

PMID- 1393713
TI  - Families at risk of child maltreatment: entry-level characteristics and growth in
      family functioning during treatment.
AB  - Research suggests that perinatal screening and early intervention may reduce the
      incidence of maltreatment and improve the parenting in at-risk families. The
      question of whether families with different sets of entry-level characteristics
      differ in the way that they respond to intervention is asked in this paper. We
      investigated whether entry-level family functioning and family problems had an
      impact on length of time in treatment and the improvement or deterioration of
      family functioning over time. In our analyses, we used entry-level
      characteristics to classify families into five homogeneous groups--situationally
      stressed, chronically stressed, emotionally stressed, multirisk, and violent
      multirisk--and we found that treatment duration and rate of change in family
      functioning over time differed in clinically important ways across these groups.
      Our findings suggest that treatment is likely to be successful in stabilizing and
      slowly improving the family functioning of the majority of families at risk of
      child maltreatment.

PMID- 1393715
TI  - Discovering physical abuse: insights from a follow-up study of delinquents.
AB  - In a follow-up study of incarcerated Connecticut youth, 66 subjects participated
      in extensive personal interviews. This paper documents discrepancies between
      early data regarding abuse and retrospective self-reports of abuse given at the
      time of follow-up. It describes the development of an interview protocol in which
      inquiries regarding medical history, the general temperament of caretakers and
      their behaviors when intoxicated, and instruments and methods of punishment used
      in the home enabled subjects to describe abusive experiences not disclosed in
      response to direct questions about maltreatment. The paper also discusses the use
      of explicitly worded probes to flesh out a clear picture of subjects'
      experiences. The conflicts that underlie denial or minimization of abuse are
      discussed, along with interviewing strategies for overcoming them.

PMID- 1393714
TI  - University-based interdisciplinary training in child abuse and neglect.
AB  - This article presents an overview of the 10 university-based interdisciplinary
      training programs in child maltreatment funded in 1987 by the National Center on
      Child Abuse and Neglect. The organizational structure, student composition, and
      academic requirements of the program are described. A more detailed description
      of one of the programs based in a medical school is presented as a model for
      replication. The specific clinical and didactic components of the program's
      curriculum are included. Additionally, recommendations for replicating an
      interdisciplinary graduate training program in child abuse and neglect are
      discussed.

PMID- 1393716
TI  - Medical evaluation referral patterns for sexual abuse victims.
AB  - It has been recommended that all children suspected of being sexually abused
      should have medical evaluations. To better understand practices and perceptions
      of child sexual abuse medical evaluations, a survey was conducted of 579
      professionals attending educational programs on child sexual abuse; 85.8% (N =
      497) responded. Half (50%) of the respondents reported no previous training in
      child sexual abuse. Of the 336 nonphysician professionals, 194 (57.7%) were in
      positions where they make referrals of the victims, and 69% of these did not
      refer all of the children they saw for medical evaluations. The first referral
      choice for medical evaluation was most often to the victim's primary physician
      (57%). For those professionals who did not refer all alleged victims for medical
      evaluation, neither the victims' age, gender, nor accessibility to care were
      generally considered relevant in determining the decision to refer. However, the
      type of abuse and presence of physical and psychological symptoms were considered
      relevant in making the decision. The majority indicated that the findings of the
      medical exam were very useful in substantiating or refuting the allegation of
      abuse. Further training for both medical and nonmedical professionals is needed
      to increase awareness of the need for and implications of the medical evaluation
      if children are to receive comprehensive assessments. Physicians may play an
      active role in this process through education of professionals and provision of
      care.

PMID- 1393717
TI  - Child abuse by mothers' boyfriends: why the overrepresentation?
AB  - This study showed that although mothers' boyfriends perform relatively little
      child care, they are responsible for substantially more child abuse than other
      nonparental caregivers. Using data drawn from interviews with single mothers and
      records of child abuse substantiated through child protection investigation,
      mothers' boyfriends' overrepresentation in child abuse was traced to five
      conditions: (a) the location of their child care in single parent families; (b)
      their gender; (c) the absence of genetic relationship between mothers' boyfriends
      and their partner's children; (d) mothers' boyfriends' perceived illegitimacy as
      caregivers and family members; and (e) mothers' boyfriends' rivalry with their
      partner's children. The limitations of these findings and implications for future
      research are discussed.

PMID- 1393718
TI  - Ego development in women with histories of sexual abuse.
AB  - As many as a third of the women in this culture experience sexual abuse prior to
      reaching age 18. Recent literature and research have presented divergent views
      related to the impact of early abuse on ego development, with arguments
      supporting both ego fragmentation and ego acceleration. This preliminary study
      compared the level of ego development, as measured by Loevinger's Washington
      University Sentence Completion Test (SCT), of 30 women with histories of
      childhood sexual victimization, and 30 women with no history of abuse. Results
      indicated no significant difference between the ego levels of the sexually abused
      and nonabused groups, with a slight trend toward higher ego development in the
      abused group. Factors contributing to these findings are discussed and
      recommendations for future research are suggested.

PMID- 1393719
TI  - Long-term effects of incest: life events triggering mental disorders in female
      patients with sexual abuse in childhood.
AB  - The authors studied several psychosocial, psychosomatic, and psychodynamic
      factors in 33 female psychiatric patients who had been victims of incest. Abuse
      was almost exclusively severe and prolonged. Three quarters of the female
      patients had been abused by their biological fathers or stepfathers. Sexual abuse
      experiences in childhood are connected with feelings of anxiety, helplessness,
      and powerlessness. Together with a lack of support on the part of the mother,
      these experiences lead to ego weakness, an autoplastic mode of coping with
      aggression and to patterns of objectal relationships which predispose them to
      object loss. The links between a girl's traumatic experiences in relationships
      and her vulnerability to separation in later life and their importance for the
      incidence of mental disorders will be discussed on the basis of Bowlby's
      attachment theory.

PMID- 1393720
TI  - Network therapy using videotape disclosures for adult sexual abuse survivors.
AB  - Treatment of childhood sexual abuse survivors may be enhanced by a technique
      designed to generate a therapeutic constituency for the survivor around the
      disclosure of childhood abuse experiences. The need for validating relationships
      is hypothesized as a condition for successful treatment. The videotaped
      disclosure process proceeds in five stages: (1) Deciding to make a tape, (2)
      making a videotape following a semistructured interview format, (3) the patient
      viewing the tape, (4) showing the tape to potential therapeutic team members, and
      (5) possibly using the tape for a confrontation with the abuser. The technique
      has been used on 27 cases. Case histories are given to illustrate the procedure.
      Discussion includes potential mechanisms of action and issues in treatment that
      arise with the use of the method described.

PMID- 1393721
TI  - Countertransference in the family therapy of survivors of sexual abuse.
AB  - As family therapy of sexual abuse survivors has become more common, theoretical
      and technical issues have received considerable attention. Less attention has
      been devoted to the countertransference experience of the therapist. Unexamined
      therapist countertransference is a critical element in the treatment of these
      families, which markedly influences the nature and direction of treatment.
      Particular types of countertransference are presented here. In addition, the
      contention is made that countertransference is not only evoked by the particular
      presentation of the family members, but also by the therapist's unexplored
      political and moral beliefs.

PMID- 1393722
TI  - Juror and expert knowledge of child sexual abuse.
AB  - Mental health professionals with expertise in child sexual abuse (CSA) often
      testify as expert witnesses in court. There is significant controversy over the
      admissibility of this type of evidence. To be admissible, the testimony of an
      expert must be beyond the common knowledge of the jury and based on information
      generally considered to be reliable within the professional community in which it
      is used. To date, no empirical data have existed to allow courts to make an
      informed judgement as to the extent of either juror knowledge or professional
      acceptance of CSA data. The present study addresses this issue. Jurors and
      experts completed a questionnaire designed to reveal their understanding of CSA.
      Results indicate that experts demonstrated strong consensus on 29 of 40 items
      included in the questionnaire, and that relative to experts, jurors have limited
      knowledge of these issues. These results suggest that many of the scientific
      findings concerning CSA are reliable and that the information is often beyond the
      common knowledge of the jury. These findings argue for the use of expert
      testimony in select cases of child sexual abuse.

PMID- 1393723
TI  - Fatality after report to a child abuse registry in Washington State, 1973-1986.
AB  - Between 1973 and 1986, 11,085 children born in Washington State were reported to
      the state child abuse registry. We analyzed the fatality rate subsequent to
      reported abuse for this cohort of children compared to a population of nonabused
      children matched on sex, county of birth, and year of birth. Children reported to
      the child abuse registry had an almost threefold greater risk of death than the
      comparison population. A report of physical abuse carried the greatest risk of
      subsequent death. However, the relative risks were also elevated for children who
      suffered neglect or sexual abuse. Children reported to the registry were almost
      20 times more likely than the comparison population to die from homicide.
      Children less than 1 year of age at time of reported abuse had the highest
      fatality rate subsequent to abuse, but adolescents had the highest relative risk
      for fatality after abuse, compared to the population of nonabused children. Rates
      of fatality subsequent to abuse were equal for males and females. Although this
      study could not measure the extent to which any given intervention reduced the
      risk of subsequent fatality in abused children, registries can serve a valuable
      function in identifying subpopulations at risk and quantifying that risk relative
      to the general population.

PMID- 1393724
TI  - Evaluating risk assessment implementation in child protection: issues for
      consideration.
AB  - The use of systematic risk assessment models by Child Protective Services is a
      rapidly growing phenomenon. Despite their popularity, we know little about the
      effect of implementation on casework practice. This article examines some issues
      that agencies might consider when evaluating the impact of risk assessment
      implementation on service delivery. The authors recommend an approach that
      includes the use of qualitative and quantitative measures in a process and an
      outcome evaluation to determine the degree to which the model has been
      implemented as intended and the impact of implementation on the case work
      process. Though this approach is likely to provide agencies with detailed
      information of the impact of risk assessment implementation, caution is
      recommended when interpreting the results from an evaluation of a risk assessment
      model in a field setting.

PMID- 1393726
TI  - Substantiation of reported child abuse or neglect: predictors and implications.
AB  - Underreporting and overreporting of suspected child abuse and neglect cases
      reduce the efficiency of child protection services. We used all the reports in
      South Australia for 1988-1989 (N = 3,228) to study the determinants of the
      decision by child protection workers to register a reported incident as being one
      of child abuse and neglect. Logistic regression showed that registration
      (substantiation) was predictable from two variables: the age of the alleged
      victim and the caseworker's estimate of severity. This latter variable needs
      investigation, as despite its crucial role we have no information on how
      caseworkers form a judgment about severity.

PMID- 1393725
TI  - Childhood history of abuse and child abuse screening.
AB  - Although a childhood history of abuse is related to parental child abuse, many
      parents with a history of abuse are not abusive. To determine the effects of a
      childhood history of abuse on adult child abuse potential, a modified Conflict
      Tactics Scale (CTS) and the Child Abuse Potential (CAP) Inventory were
      administered to matched groups of physically abusive mothers with a childhood
      history of abuse, nonabusive comparison mothers with a childhood history of
      abuse, and nonabusive comparison mothers without a childhood history of abuse.
      The modified CTS asked about childhood events and was used to confirm a childhood
      history of abuse. As expected, the CTS verbal and violence scales were higher for
      the abusive and nonabusive mothers with a childhood history of abuse. None of the
      CTS scores were different for the abusive and nonabusive mothers with a childhood
      history of abuse. In contrast, the CAP abuse scores distinguished between all
      three study groups. However, on the CAP factor scales, only the rigidity and
      unhappiness factors discriminated between abusive and nonabusive mothers with a
      childhood history of abuse. Nonabusive mothers with a childhood history of abuse
      were less rigid in their child expectations and were happier in their
      interpersonal relationships than abusive mothers with a childhood history of
      abuse.

PMID- 1393727
TI  - Physically abusive parents and the 16-PF: a preliminary psychological typology.
AB  - A typology of physically abusive parents was developed based upon personality
      characteristics measured by the 16-PF. Cluster analysis revealed five distinct
      patterns, accounting for 81 of 82 profiles submitted. Significant differences
      among the clusters were found on 14 of the 16 factors. The following types were
      described: (a) Shy, withdrawn, apprehensive, sober, and restrained; tending to
      have the least education, the greatest number of children. (b) Parents presenting
      as "normal" in personality features; tending to have relatively more education,
      fewer children. (c) Compulsive, bold, dominant, and assertive; tending to be
      highly manipulative in self-presentations, have high educational levels, and be
      older than other types. (d) Basically passive and submissive; tending to come
      from families where both parents are abusive. (e) Isolated, withdrawn,
      suspicious, tense, and apprehensive; tending to be more psychologically
      disturbed. Significance tests on external variables performed to validate the
      solution found differences among clusters in age, education, number of children,
      number of parents involved in abuse, 16-PF Faking Good and Faking Bad scores, and
      MMPI Scales L, F, K, 4, 5, 6, 7, and 0. Distinguishing personality features and
      demographic characteristics of the types are discussed with a focus upon possible
      treatment approaches for each type. Limitations of the study and suggestions for
      future research are addressed.

PMID- 1393728
TI  - Progress and issues in the implementation of the 1984 out-of-home care protection
      amendment.
AB  - The purpose of this paper is to assess the status of implementation of out-of
      home protection programs since 1984 in the U.S. Data was obtained from a survey
      of state child protection services (CPS) liaisons in summer, 1989. A framework
      for viewing protection after placement is presented and the development of policy
      regarding maltreatment in out-of-home care is traced from its roots in the
      deinstitutionalization movement. Changes in state statutes and rules, results in
      out-of-home abuse and neglect reporting, how states operationalize "properly
      constituted authority" and "independent investigation," the role of licensing in
      preventing and remediating out-of-home maltreatment, training initiatives and the
      extent of the use of background checks are reported. A summary evaluation of the
      status of the implementation of the federal 1984 out-of-home care protection
      amendments by state agencies is offered.

PMID- 1393730
TI  - Agreement among professionals about a child's sexual abuse status: interviews
      with sexually anatomically correct dolls as indicators of abuse.
AB  - This study was designed to define clinicians' ratings of the comments, behaviors,
      and affects of abused children and compare them with the same clinicians'
      decisions about the child's abuse status. The authors concluded that sexually
      anatomically correct dolls used alone are inadequate in providing enough
      information for professionals to accurately assess the abuse status of young
      children. Also it is unclear what observations of the child by mental health
      professionals are best correlated with their determinations of a child's abuse
      status. Of concern was the finding that the mental health professionals were more
      likely to be in agreement with the interviewer's determination of abuse than with
      the actual status of the child, suggesting undue influence of the interviewer,
      or, alternatively, both observer and interviewer were responding to unidentified
      child factors.

PMID- 1393729
TI  - Mother's age and risk for physical abuse.
AB  - It is widely believed that young mothers are at greater risk of engaging in
      physical abuse. However, this relationship is not clearly supported by previous
      empirical research. This study reexamines the issue using a nationally
      representative sample of 1,997 mothers. All analyses controlled for family
      income, race, number of minor children in the home, age of abused child, mother's
      education, and whether mother was a single parent. Physical abuse was measured
      with the Conflict Tactics Scales. Using mother's age at time of birth of the
      abused child, the younger the mother, the greater the rate of child abuse;
      however, there was not a significant relationship when mother's age was measured
      at age at time of abuse. Large families and minority group children were also
      found to be at greater risk of abuse. The paper discusses implications for
      further research and for prevention of child abuse.

PMID- 1393731
TI  - Professionals' standards of "normal" behavior with anatomical dolls and factors
      that influence these standards.
AB  - Do professionals have a consistent standard of what constitutes normal behavior
      with anatomical dolls? To answer this question, 201 professionals who work with
      child sexual abuse victims were asked to rate the normalcy of various behaviors
      with the dolls for nonabused children ages 2 to 5.9 years. The majority of
      respondents agreed that overtly sexual behaviors, such as demonstrating oral
      genital contact or vaginal intercourse, were abnormal for nonabused children. For
      less obvious behaviors, such as touching the sex parts of dolls, there was more
      disagreement among professionals about what these behaviors mean. The ratings of
      these ambiguous behaviors varied depending on profession of the respondent,
      gender of the respondent, and number of years of experience. Law enforcement
      professionals, women, and those with the least amount of experience were more
      likely to view ambiguous behaviors as abnormal. These findings are discussed in
      the context of past research, with suggestions for future studies.

PMID- 1393732
TI  - Sexual abuse by grandparents.
AB  - Using a sample of 95 case records of sexual abuse substantiated through child
      protection investigation, this study confirmed several findings from earlier
      studies of sexually abusive grandparents: (a) virtually all perpetrators are
      male, (b) the vast majority of victims are female, (c) a disproportionately large
      share of abusive grandfathers appear to also be sexually abusive fathers, and (d)
      stepgrandchildren appear to experience greater risk. Additionally, it was noted
      that stepgrandparent perpetrators were more threatening and physically violent.
      However, contrary to some earlier studies, evidence was provided that this form
      of abuse is inappropriately described as "gentle." Explicit threats and overt
      physical assault were noted in 14 cases. Moreover, the other tactics used to gain
      children's compliance, such as overpowering them, suddenly grabbing their
      genitals, and attacking them in their sleep, appeared to seriously compromise
      children's autonomy and personal integrity.

PMID- 1393733
TI  - Protective personality characteristics among adolescent victims of maltreatment.
AB  - The purpose of this research was to examine whether personality characteristics,
      locus of control orientation, and self-esteem were protective against depression
      among female adolescent victims of maltreatment and to examine whether the
      presence of these characteristics was related to the age of the victim when
      maltreatment began. Thirty-three maltreated adolescent females and a comparison
      group of 112 nonmaltreated female adolescents were administered a questionnaire
      containing scales measuring locus of control orientation, self-esteem, and
      depression. Results revealed that personality characteristics interacted with
      maltreatment status in predicting depression, suggesting that they are protective
      factors. Results also revealed that adolescents who first experienced
      maltreatment during childhood were significantly less likely than those who first
      experienced maltreatment during adolescence to have these protective personality
      characteristics.

PMID- 1393734
TI  - Behavioral problems in alleged sexual abuse victims.
AB  - This study was conducted to compare the parental assessments of problem
      behaviors, using the Achenbach Child Behavior Checklist, among alleged sexual
      abuse victims (n = 81) and an age, race, and gender matched group of nonabused
      comparison subjects (n = 90). Alleged sexual abuse victims demonstrated
      significantly higher mean total behavior problem, internalizing and externalizing
      scores than the comparison sample. Subscale profiles were all in the direction
      consistent with withdrawal, impairment in social interaction, and sexual
      problems. Item comparison indicated that sexual abuse victims were more likely to
      be assessed as having some problem behaviors that have been reported as being
      indicative of sexual abuse. A significant difference was not obtained on several
      behaviors that have been previously reported as indicative of sexual abuse. These
      findings support concerns that sexual abuse victims do exhibit more problem
      behaviors, but caution must be exercised when interpreting individual behaviors
      because of their frequency in a nonabused sample.

PMID- 1393735
TI  - Nationwide practices for screening and reporting prenatal cocaine abuse: a survey
      of teaching programs.
AB  - Questionnaires surveying policies and opinions about prenatal cocaine abuse were
      sent to training programs nationwide. Eighty-one pediatric and 81 obstetric
      programs from 42 states responded. Although respondents favored routinely
      screening all patients by maternal history (81%) and by urine toxicology (36%),
      only 64% and 8%, respectively, reported these as established policy. Physicians
      reporting higher regional prenatal cocaine abuse rates more commonly favored
      universal perinatal screening (p = .009), but established policies were similar
      regardless of local prevalence (p = .19). Fifty-two percent of respondents were
      unaware of their state's requirements for reporting prenatal cocaine abuse. While
      most physicians favored interventions such as voluntary drug rehabilitation (64%)
      and family support services (64%), some physicians favored foster care placement
      for the infants (28%) and involuntary drug rehabilitation (31%). Only 3% felt
      that criminal prosecution of the mother was appropriate. Policies for managing
      prenatal cocaine abuse often did not reflect physicians' opinions. A
      multidisciplinary medical, social, and legal approach is needed to develop
      effective management policies.

PMID- 1393736
TI  - Child Protection Registration and siblings, diagnosed as sudden infant death
      syndrome (SIDS)

PMID- 1393737
TI  - [Polymorphism of HLA class I loci HLA-A, -B, -C, in the Mandenka population from
      eastern Senegal].
AB  - A sample of 162 Mandenkalu from Eastern Senegal has been typed for three HLA
      class I loci: HLA-A, -B and -C. The Mandenka population presents a very high
      genetic variability with 15 alleles for locus A, 24 alleles for locus B, and at
      least 8 alleles for locus C. The calculated heterozygosities for the three loci
      A, B, and C are respectively 0.884, 0.944 and 0.829. The Mandenkalu allelic
      frequencies are close to that found in other sub-Saharan populations. They show,
      however, some peculiarities like the occurrence of the Bw 56 allele and the high
      frequencies of both B5 and B35.

PMID- 1393738
TI  - [Production of hyaluronan-binding glycoprotein by human monocytes. Its use as
      marker in myeloid leukemia].
AB  - A hyaluronan-binding protein fraction was isolated by affinity chromatography of
      peripheral human blood mononuclear cell culture medium through immobilized
      hyaluronan. The presence of a hyaluronan-binding protein similar to human brain
      hyaluronectin was demonstrated by (i) the ELISA method on hyaluronan-coated
      plastic plates using anti-hyaluronectin antibodies, (ii) the lowering of the
      elution volume of the protein on liquid gel chromatography in the presence of
      hyaluronan, (iii) the extinction of the reaction to human brain hyaluronectin
      when antibodies were absorbed out with monocyte hyaluronectin, (iv) western
      blotting with polyclonal and monoclonal anti-hyaluronectin antibodies. The
      hyaluronectin-producing cells were adherent (10 min., 37 degrees C) to plastic,
      esterase (+) and CD 14 (+) cells and had the morphology of monocytes. The protein
      expression was investigated in leukemic cells by means of the immunocytochemical
      method. Hyaluronectin expression was restricted to 4/12 of M4 and M5 types of
      acute myeloid leukemias. Other myeloid leukemia and acute lymphoblastic leukemia
      cells were negative. The results indicate that hyaluronectin can be produced
      under free form in the absence of hyaluronan, by human peripheral blood
      monocytes. It supports the hypothesis that the expression of hyaluronectin in
      tumour stroma could be due, at least in part, to inflammatory cells of the
      tumour. The expression of the protein by M4 and M5 acute myeloid leukemia cells
      suggests that hyaluronectin could be synthesized by immature cells of the
      monocytic lineage as well as by mature monocytes.

PMID- 1393739
TI  - [Fragmentation of fibronectin in cystic fibrosis].
AB  - Fibronectin (FN) plays an important role in mediating cell-matrix interactions
      and also as an opsonin in the phagocytosis of some microorganisms. Due to its
      domain structure FN is easily attacked by proteolytic enzymes and especially by
      elastases. Some of the fragments possess original properties as potentiation of
      viral transformation or proteolytic activity absent in the intact molecule.
      Cystic fibrosis is frequently accompanied by infection with protease generating
      microorganisms, such as Pseudomonas aeruginosa. Polyacrylamide gel
      electrophoresis and immunoblotting revealed the presence of FN fragments in the
      plasma of patients with molecular weight between 30 and 100 kD. Purified plasma
      FN was rapidly hydrolyzed in fragments by the sputum of patients as well as by
      purified Pseudomonas elastase. The comparison of fragments detected in patients'
      plasma with those produced by in vitro proteolysis confirms the probability of in
      vivo fragmentation of FN in cystic fibrosis and suggests that several proteolytic
      enzymes, endogenous and of bacterial origin, might be involved.

PMID- 1393740
TI  - [Epidemiological observations on iridovirosis of Lymnaea truncatula, host
      mollusca of Fasciola hepatica].
AB  - Epidemiological studies were carried out in 11 populations of Lymnaea truncatula
      in 1983-1984 and 1987-1989 to determine the prevalence of snail infection by an
      iridovirus. The virus was found in the different populations and samples, with a
      frequency ranging from 1.6 to 87%. The virosis would be endemic.

PMID- 1393741
TI  - The challenge of ovarian cancer.

PMID- 1393742
TI  - Advances in the screening and treatment of ovarian cancer.
AB  - Ovarian cancer is the leading cause of death from gynecologic malignancies. This
      article reviews the newer chemotherapeutic agents and treatment strategies
      available to the practicing clinician. Also discussed are the benefits and
      shortfalls of the various options for screening, such as ultrasound and tumor
      markers, as well as the data supporting oral contraceptives and the controversy
      surrounding prophylactic oophorectomy.

PMID- 1393743
TI  - Colonoscopy.
AB  - Colonoscopy is an accepted technique for investigation of the colon. No portion
      of the large bowel is inaccessible to the diagnostic and therapeutic approach by
      flexible colonoscopy. The technical aspects of instrumentation have yielded to
      progress, with a small television chip currently incorporated into the tip of
      endoscopes transmitting an excellent image of the colon. Primary colonoscopy is
      being performed for selected indications, and, as facility with the technique
      increases, there will be a greater tendency for the performance of primary
      colonoscopy. Interruption of the adenoma-carcinoma sequence by techniques of
      snare-polypectomy may serve to markedly decrease the incidence of colon cancer
      over the next generation.

PMID- 1393745
TI  - Endotracheal intubation.
AB  - Endotracheal intubation can be accomplished by several different methods, which
      are discussed herein. Special considerations such as the obstructed tube, air
      leakage around the tube, tube replacement, and drug therapy are also reviewed, as
      are the indications for tracheostomy, the use of double lumen tubes, and
      fiberoptic laryngoscopy or bronchoscopy.

PMID- 1393744
TI  - Using a population-based cancer reporting system to evaluate a breast cancer
      detection and awareness program.
AB  - During May 1987, a total of 10,207 Wisconsin women were screened as part of a
      statewide Breast Cancer Detection and Awareness program sponsored by the
      Wisconsin Division of the American Cancer Society. Data from a population-based
      cancer reporting system were used to predict the number of expected breast cancer
      cases for that year. After controlling for secular and seasonal trends, we found
      that, compared with the number of cases that would have been expected, 51 more
      cases of localized breast cancer were diagnosed in the state during the time of
      the program. This study demonstrates the public health impact of a statewide
      screening program and the usefulness of a cancer reporting system in program
      evaluation.

PMID- 1393746
TI  - Central venous catheterization in the critically ill patient.
AB  - Central venous catheter placement for access and monitoring purposes is one of
      the most commonly performed procedures in the intensive care unit. This article
      details the indications, techniques, and advantages and disadvantages associated
      with various approaches to central line insertion; complications associated with
      central venous line insertion are also reviewed briefly.

PMID- 1393747
TI  - Temporary transvenous cardiac pacing.
AB  - Temporary cardiac pacing in the critical care setting can be a lifesaving
      intervention in a number of clinical situations. A variety of catheter types and
      pulse generators are available. Insertion techniques include the use of
      fluoroscopic imaging, intracavitary ECG monitoring, and blind advancement with
      surface ECG monitoring. This article focuses on the indications, equipment,
      techniques, complications, and troubleshooting of temporary transvenous cardiac
      pacemakers.

PMID- 1393748
TI  - Peritoneal catheterization.
AB  - Procedures involving invasion of the peritoneal cavity are often performed on
      critically ill or injured patients. Like any invasive procedure, they require a
      thorough understanding not only of their techniques and indications, but also of
      their contraindications and complications. Used appropriately, these procedures
      may serve as invaluable diagnostic or therapeutic tools in the care of acutely
      ill patients.

PMID- 1393749
TI  - Sengstaken-Blakemore tube placement. Use of balloon tamponade to control bleeding
      varices.
AB  - The management of acute variceal bleeding continues to challenge those who care
      for patients with portal hypertension. Survival depends on rapid institution of
      an established protocol for resuscitation, diagnosis, and management of the
      patient. Balloon tamponade plays an important part in the management of this
      problem along with pharmacologic and endoscopic modalities. It is important in
      closing, however, to note that guidelines for use cannot compensate for lack of
      experience and the authors agree with Vlavianos and colleagues in stating that
      without experience in its use, balloon tamponade is of limited value.

PMID- 1393750
TI  - Fiberoptic bronchoscopy in the intensive care unit.
AB  - The primary uses of FFB in the intensive care unit are in the diagnosis of
      opportunistic infection and for airway management. In addition, use of PTC brush
      or BAL with quantitative cultures may allow identification of the specific cause
      of bacterial pneumonia. Determination of the location and cause of pulmonary
      hemorrhage is possible in the intubated patient without massive hemoptysis. Use
      of FFB in atelectasis is more controversial and less commonly encountered. Other
      uses include foreign body retrieval, tamponade of bleeding segments and
      diagnosis/treatment of BPF. In addition to development of technical skills and
      knowledge of the indications for FBB, critical care physicians should be aware of
      contraindications and potential complications, as well as steps to minimize the
      latter.

PMID- 1393751
TI  - Pulmonary artery catheterization.
AB  - After two decades, hemodynamic invasive monitoring using a flow-directed, balloon
      tipped, pulmonary artery (PA) catheter has established itself as a significant
      component of acute clinical care. In spite of continued recommendations for
      limitations, restrictions, moratoria, and even abandonment, growth in catheter
      use continues. Attempts to replace it by competing technologies for routine
      clinical practice have not been successful thus far. More than one million PA
      catheters are inserted in the United States annually. The clinical utility and
      value of the pulmonary artery catheter depend largely on the interpretation of
      information obtained. Clinical interpretation of data is influenced by an
      understanding of cardiopulmonary hemodynamics, technical skills, and professional
      integrity of the physician using the device. After a brief history, this article
      focuses on the technical aspects of the insertion procedure, choice of hardware,
      and acquisition and analysis of information. Indications, contraindications, and
      clinical utility are briefly described. Major complications from PA
      catheterization reported in the literature since clinical introduction of the
      catheter are summarized.

PMID- 1393752
TI  - Peripheral vascular cutdown.
AB  - Critically ill patients who are not candidates for percutaneously placed arterial
      and venous lines require surgical cutdown. Although significant complications may
      arise from inadvertent injury to the vessel or associated structures during
      arterial and venous cutdown, these complications can be minimized by meticulous
      technique. With attention to site selection and catheter care, the useful life of
      these complex catheters approaches that of percutaneously placed devices.
      Finally, although the sequelae of placement by these techniques--including wound
      and catheter infection, distal ischemia, and vessel ligation--are increased, the
      need for appropriate intravascular access in these patients far outweighs the
      potential risks.

PMID- 1393753
TI  - Percutaneous intra-aortic balloon counterpulsation.
AB  - Intra-aortic balloon pumping is the mainstay in the management of acute left
      ventricular dysfunction in the critical care setting. Percutaneous insertion
      affords rapid initiation of the procedure. Complications are in greatest part
      vascular and infectious. The advent of new-generation, totally automatic, closed
      loop IABP systems offers the prospect of increasing the effectiveness of IABP
      support under most conditions, and especially during arrhythmias. This and other
      developments suggest that despite its standing as the most widely used temporary
      cardiac assist device, IABP has still to realize its full therapeutic potential.

PMID- 1393754
TI  - Defibrillation and cardioversion.
AB  - To optimize the success of defibrillation, the clinician needs to minimize
      impedance, choose the proper energy level, apply the proper interface, select the
      appropriate paddle size, and deliver the shock at the earliest possible time.
      Other factors that may contribute to effective defibrillation include
      defibrillation during exhalation, maintenance of an effective airway, and
      correction of electrolyte abnormalities. Open chest defibrillation can be
      achieved at a lower dose of between 10 J and 20 J. Automated external
      defibrillators have increased survival of prehospital arrests. Cardioversion can
      generally be accomplished safely either as an elective or emergent procedure.
      Selection of the proper indications, protection of the airway, anticoagulation if
      necessary, correction of digitalis toxicity, and the utilization of adjuvant
      therapy ensure an optimal outcome.

PMID- 1393755
TI  - Nasogastric and nasoenteric intubation.
AB  - Among the most commonly performed nonvascular procedures in hospitalized patients
      are the placement of nasogastric tubes and nasoenteric feeding tubes. Large-bore
      nasogastric tubes are commonly used for both diagnostic and therapeutic purposes;
      small-bore nasoenteric tubes are used primarily for intestinal feeding. The
      techniques of insertion, methods of ensuring proper positioning, and the
      potential complications of these devices are similar, and thus they are reviewed
      together in this article.

PMID- 1393756
TI  - Chest tube thoracostomy.
AB  - Knowledge of the indications, placement, and management of chest tubes in the
      intensive care unit is essential for the care of the critically ill patient.
      Awareness of the complications and mechanical difficulties that can occur with
      chest tubes and their drainage systems is essential for the safe and effective
      use of these devices.

PMID- 1393757
TI  - Objective assessment of allergenicity of infant feeding formulae.

PMID- 1393758
TI  - How predictive of asthma is atopy?

PMID- 1393759
TI  - Comparative efficacy of house dust mite extermination products.
AB  - The acaricidal efficacy of nine marketed products, i.e. Acardust, Acarosan (foam
      and powder), Actelic 50, Artilin 3A (spirit and water base), liquid nitrogen,
      Paragerm AK, and Tymasil, and of intensive vacuum-cleaning have been compared on
      four different test surfaces: mattress, tufted carpet, gypsum board and rough
      wooden board, all covered with artificial house dust. They were inoculated with
      the house dust mite, Dermatophagoides pteronyssinus or the house-dust fungus
      Aspergillus repens for evaluation of the fungistatic claims of some products. The
      acaricidal activity of Tymasil did not surpass that of vacuuming; its fungistatic
      effect was not apparent. The other products showed complete to almost complete
      eradication on at least one of the substrates tested. Taking into account the
      results of acaricidal efficacy as well as the data on safety and practicality
      acquired earlier, Acarosan powder was considered first choice for carpet
      treatment. Acarosan and liquid nitrogen, were found to be effective in the
      treatment of mattress, pillow, upholstered furniture and heavy curtains. On
      wooden surfaces Acarosan was found to be both effective and safe, while Acardust,
      Actelic 50, Artilin 3A (both fungistatic as well as acaricidal), liquid nitrogen
      and Paragerm also passed the efficiency test.

PMID- 1393761
TI  - How allergenic are hypoallergenic infant formulae?
AB  - In a comparative study six different protein hydrolysates, marketed as
      'hypoallergenic' infant formulae were investigated by skin prick tests, RAST,
      RAST inhibition and titrated provocation tests. When hydrolysates containing a
      high percentage of larger peptides were found to have the highest capacity to
      induce positive skin tests, provocation tests and to bind to human serum IgE
      antibodies of cow's milk allergic children. Casein hydrolysates appeared to have
      the least residual allergenic activity. We recommend that 'hypoallergenic'
      formulae should be tested in each case, before being prescribed to cow's milk
      sensitive children.

PMID- 1393760
TI  - Influence of a positive family history and associated allergic diseases on the
      natural course of asthma.
AB  - The outcome of childhood asthma was studied in a cohort of 406 asthmatic
      children, with emphasis on the influence of family history for allergic disease,
      as well as the influence of associated allergic diseases on prognosis. Sixty-two
      per cent had a positive family history for atopy. In young adulthood no
      differences, either in symptoms or lung function were demonstrated in comparison
      to subjects with a negative family history. Fifty-two per cent of the children
      had no other allergic disease, 48% had either eczema or hay fever or both. When
      subjects were stratified based on associated allergic disease, no differences in
      outcome in adulthood were revealed either. It is concluded that neither a
      positive family history, nor concurrent associated allergic diseases in the child
      contribute to the prognosis of asthma from childhood to young adulthood.
      Therefore, environmental factors as well as patient characteristics (including
      lung function level, level of bronchial responsiveness) are likely to be more
      important for the prognosis.

PMID- 1393762
TI  - Localization of the major house dust mite allergen Der p I in the body of
      Dermatophagoides pteronyssinus by ImmuStain.

PMID- 1393763
TI  - The effect of intranasal azelastine, Rhinolast, on nasal airways obstruction and
      sneezing following provocation testing with histamine and allergen.
AB  - The effect of single dose topical nasal therapy with azelastine hydrochloride
      (azelastine) on the response of nasal airways resistance (NAR) to provocation
      testing was studied in 36 patients with seasonal allergic rhinitis. Nasal
      provocation testing (NPT) with histamine or grass pollen was performed after a
      single dose of azelastine, 0.28 mg to each nostril, or placebo. NAR was assessed
      by rhinomanometry for 10 hr following NPT. Compared to placebo the NAR response
      to histamine was inhibited at both 1 and 2 hr following azelastine
      administration, significant at 1 hr (P less than 0.02) and 2 hr (P less than
      0.0001). No such effect was observed in relation to allergen-induced changes in
      NAR. Azelastine also inhibited numbers of sneezes for up to 10 hr following both
      histamine NPT (P less than 0.02) and allergen NPT (P less than 0.05), when
      compared to placebo. Forty-seven per cent of participants experienced bitter or
      unpleasant taste sensations after azelastine administration but no other unwanted
      effects were clearly related to azelastine therapy.

PMID- 1393765
TI  - Physician-assisted death: a flawed approach.

PMID- 1393764
TI  - The allergen specific B-cell response during immunotherapy.
AB  - The paper examines the allergen specific B-cell response in peripheral blood from
      patients undergoing immunotherapy with house dust mite extract. The 12 patients
      were part of a double blind placebo controlled study, and they were treated with
      either Dermatophagoides pteronyssinus (n = 4), Dermatophagoides farinae extract
      (n = 3) (Alutard SQ, ALK, Denmark) or placebo (n = 5). Blood was taken every
      fortnight on day seven after hyposensitization and tested for IgM, IgG, IgA and
      IgE antibody secreting cells (AbSC) to D. pteronyssinus and D. farinae allergens
      and for the total number of immunoglobulin secreting cells (IgSC). The data
      showed a maximum of approximately 120 Der f I+II specific AbSC/10(6) mononuclear
      cells (MNC). A comparison of specific AbSC to the major allergens of the two
      house dust mites demonstrated that there was no measurable species specificity in
      the B-cell response that could be correlated to immunotherapy with either of the
      two extracts. The specific IgM, IgG, and IgA response to Der f I+II was examined
      in the placebo (39 measurements) and the actively treated (56 measurements)
      groups, and the results demonstrated a significant rise in specific IgM and IgA
      AbSC following immunotherapy. The number of specific IgG AbSC did not change.
      There was a mean of less than one specific IgE AbSC/10(6) MNC, and no detectable
      change following the treatment. It is speculated that immunotherapy to inhalant
      allergens causes the induction of specific IgA AbSC. It would then be these
      partly differentiated plasma cells that are detected on their way to the
      bronchial or gut mucosa to exert their protective function mediated by allergen
      specific secretory IgA.

PMID- 1393766
TI  - Death with dignity: a difficult ethical issue.

PMID- 1393767
TI  - RNs testify at DHS hearing: 'our patients need protection!'.

PMID- 1393768
TI  - FDA safety alert: ways to avoid needlesticks while using i.v. sets.

PMID- 1393769
TI  - Enhanced precision with dual-energy X-ray absorptiometry.
AB  - Repeat spine and femur measurements (5 per case) were done on 19 subjects with
      the DPX-L densitometer operating at 3 mA giving a radiation flux fourfold higher
      than the earlier DPX model. The precision for spine bone mineral density (BMD)
      was about 0.55% (L2-L4) and 0.48% (L1-L4) for 2-minute scans (2.4 mrem). The
      precision was only slightly lower (0.4-0.5%) for 4-minute scans (5 mrem) in a
      subset of 11 subjects. There was a slight precision advantage for the larger L1
      L4 area compared with L2-L4 for 2-minute scans, but no advantage for 4-minute
      scans. The precision for femoral neck BMD was 1.00 and 0.85% for 2- and 4-minute
      scans, respectively, with proper positioning. The corresponding values for the
      Ward's triangle region of the femur were 2.6 and 1.5%. The precision of spine
      scans was influenced chiefly by variable region location. The precision of femur
      scans was affected by both patient positioning and location of the region. The 4
      minute scans minimized the number of operator changes necessary for analysis.
      Precision errors can be reduced by up to 50% with utilization of the higher flux,
      but this does not obviate the need for care in patient positioning and scan
      analysis.

PMID- 1393770
TI  - Nasal human calcitonin for tumor-induced hypercalcemia.
AB  - We treated four hypercalcemic cancer patients by nasal hCT, 3 x 2 mg daily, which
      has been reported to be active in Paget's disease at lower doses. Only one
      patient became normocalcemic and mean (+/- SEM) calcium levels fell from 11.6 +/-
      0.2 mg/dl before therapy to 10.7 +/- 0.6 mg/dl 2-3 days after starting hCT. The
      tolerance was excellent but, because of insufficient efficacy, we do not
      recommend this form of therapy for cancer hypercalcemia.

PMID- 1393771
TI  - Idiopathic juvenile osteoporosis: evidence of normal osteoblast function by 1,25
      dihydroxyvitamin D3 stimulation test.
AB  - Idiopathic juvenile osteoporosis (IJO) is a rare form of bone demineralization
      that occurs during childhood. The mechanism of bone loss is unclear. Some bone
      hystomorphometric studies have found osteoblast failure and decreased bone
      formation in the affected patients whereas others have reported increased bone
      resorption. To elucidate this issue, we studied osteoblast function in six
      patients with IJO (five males, one female; aged 2.3-14.6 years) and five healthy
      sex- and age-matched subjects (four males, one female; aged 2.0-15.1 years)
      measuring serum values of osteocalcin under basal condition and during an
      osteoblast stimulation test performed by oral 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] administration (1.8 micrograms/1.73 m2/daily). After a baseline day
      (day 0), all the subjects (patients and controls) received 1,25(OH)2D3 in four
      divided doses for 6 days (days 1-6). Fasting blood samples were obtained every
      morning (0800 h) for the determination of serum osteocalcin. Baseline osteocalcin
      levels were not significantly different between IJO and controls (13.58 +/- 6.05
      ng/ml versus 16.04 +/- 5.09 ng/ml, respectively) even if two patients had low
      osteocalcin values. During 1,25(OH)2D3 administration, serum osteocalcin values
      significantly increased (P less than 0.001) from baseline in both children with
      IJO and controls, reaching peak values not significantly different in the two
      groups. Our results do not support the hypothesis that defective osteoblast
      function is the primary factor of bone demineralization in IJO.

PMID- 1393772
TI  - Decrease in bone level of 1,25-dihydroxyvitamin D in women over 45 years old.
AB  - The most active metabolite of vitamin D is 1,25-dihydroxyvitamin D [1,25(OH)2D].
      Its level in the bone may play a role in the pathogenesis of metabolic bone
      diseases such as osteoporosis. To assess this, and to see whether there is
      correlation between serum and bone levels, we studied serum and bone samples
      taken from 43 patients (18 men and 25 women) undergoing different orthopedic
      procedures. Patients were studied according to sex and age groups (less than 45
      years, 46-60 years, greater than 61 years). Serum level of 1,25(OH)2D was found
      to be 29.7 +/- 2.61 pg/ml (mean +/- SEM) for women, 32.2 +/- 3.86 pg/ml for men,
      and 30.7 +/- 2.18 pg/ml for the group as a whole. No significant statistical
      differences were found among age subgroups in either sex or between sexes. Bone
      level of 1,25(OH)2D was found to be 31.5 +/- 4.46 pg/g for women, 26.5 +/- 3.06
      pg/g for men, and 29.4 +/- 2.81 pg/g for the entire group. No significant
      statistical difference was found between the age subgroups for men. However, the
      level of 1,25(OH)2D was found to be higher in the group of younger women (less
      than 45 years) compared with the older women (46-60 years and greater than 61
      years) (P less than 0.005).

PMID- 1393773
TI  - Normocalcemia with persistent increase of parathyroid hormone: a prospective
      study.
AB  - Twelve patients were followed up for 3 months after parathyroidectomy. Serial
      measurements of serum parathyroid hormone (PTH), calcium, and phosphate were
      made. Four patients had an increased serum PTH postoperatively, which was already
      apparent by the third postoperative day. All patients became normocalcemic. Their
      hyperparathyroid-like phosphate parameters indicated that we were dealing with a
      biologically active PTH. Using preoperative biochemical parameters it was
      impossible to predict which patients would have an increased PTH
      postparathyroidectomy (PTX). Probably the patients with high PTH post-PTX had
      higher parathyroid volumes. In our opinion after PTX, a normocalcemic high PTH
      situation should be avoided by 3 1/2 parathyroid gland extirpation in all cases.

PMID- 1393775
TI  - Risk for developing osteoporosis in untreated premature menopause.
AB  - The bone mineral density (BMD) of the lumbar spine and proximal femur was
      determined by dual photon absorptiometry in 32 women with untreated premature
      menopause (cessation of menses before 45 years of age). The BMD of the spine and
      proximal femur in four obese patients was not different from the BMD of the age
      matched controls. On the contrary, the BMD of the nonobese females with premature
      menopause was significantly lower with respect to the average values found in
      healthy young women, in age-matched and menopause-matched controls. The BMD
      deficit was greater over the lumbar spine than in the proximal femur. Forty three
      percent of nonobese patients were already under the vertebral fracture threshold
      and 25% of nonobese patients were below the hip fracture threshold. The BMD
      deficit in the lumbar spine was correlated to the loss observed in the femoral
      neck (r = 0.59, P less than 0.001), in the trochanter (r = 0.65, P less than
      0.001) and in the Ward's triangle (r = 0.73, P less than 0.001). A negative
      correlation was observed between years of menopause and the BMD of the lumbar
      spine (r = -0.39, P less than 0.05). The results indicate the high individual
      risk for osteoporotic fractures in nonobese females with untreated premature
      menopause. The BMD loss was greater over the skeletal areas that are
      predominantly composed of trabecular bone compared with cortical bone.

PMID- 1393774
TI  - Synthetic parathyroid hormone-like protein (1-74) is anabolic for bone in vivo.
AB  - Parathyroid hormone-related protein (PTHRP) has recently been purified from human
      tumors associated with the syndrome of humoral hypercalcemia of malignancy. The
      gene encoding PTHRP has been cloned, and based on predicted amino acid sequence,
      polypeptides comprising the first 36 [36Tyr(1-36) PTHRP amide] and 74 [(1
      74)PTHRP] amino acids have been synthesized. Human (h) PTHRP (1-36) and (1-74)
      are potent bone-resorbing agents, and are catabolic for bone in vivo when given
      continuously at high doses. Bovine parathyroid hormone (bPTH) (1-34) is also
      catabolic for bone at high dose levels, but when given in low doses for weeks to
      months, it is anabolic. Although PTHRP possess several PTH-like properties in
      bone, hPTHRP (1-34) is reported to be only weakly anabolic in vivo. As
      polypeptide length influences PTHRP action, we evaluated hPTHRP(1-74) as an
      anabolic agent for bone in vivo. Twenty-four 4-week-old male Sprague-Dawley rats
      were given daily subcutaneous injections of hPTHRP(1-74) (1 and 2 nmol/100 g body
      weight, bw), bPTH(1-34) (4 nmol/100 g bw) or vehicle. Rats were sacrificed on day
      12, and serum calcium, phosphorus, and 1,25 dihydroxyvitamin D and femoral bone
      dry weight, calcium content, and hydroxyproline content were measured. Serum
      calcium and phosphorus were equivalent in all groups. A significant increase in
      dry bone weight was observed in both PTHRP-treated groups compared with controls.
      PTHRP also caused a significant, dose-dependent increase in bone calcium and
      hydroxyproline content. Results of these studies indicate that PTHRP (1-74) is
      anabolic for bone in vivo when administered at low-dosage levels for a prolonged
      period.

PMID- 1393776
TI  - Ca2+ uptake by endoplasmic reticulum of renal cortex. II. Effects of
      uninephrectomy and parathyroidectomy.
AB  - Calcium uptake by the endoplasmic reticulum (ER) is important for cellular
      calcium homeostasis, yet its regulation in nonmuscle cells is poorly understood.
      We reported that Ca2+ uptake by a light fraction of canine renal cortical ER
      (LER) is stimulated by protein kinase C in vitro. Here we describe conditions in
      vivo that stimulate renal cortical LER Ca2+ uptake. Thirty minutes after
      contralateral nephrectomy in the dog, 45Ca2+ uptake into renal cortical LER was
      increased 42% above control LER. There was no difference in LER Ca2+ uptake 24
      hours after uninephrectomy. Acute denervation did not reproduce the increase in
      LER 45Ca2+ uptake seen at 30 minutes after uninephrectomy, nor did prior
      thyroparathyroidectomy abolish it. Forty-eight hours after
      thyroparathyroidectomy, 45Ca2+ uptake activity into renal cortical LER was
      decreased approximately sevenfold. In a proximal tubular cell line (LLC-PK1), 30
      minute incubation with 12-O-tetradecanoylphorbol-13-acetate doubled 45Ca2+ uptake
      into a nonmitochondrial pool. Pretreatment with epidermal growth factor halved ER
      Ca2+ uptake, whereas insulin-like growth factor and growth hormone, alone or in
      combination, had no effect. Our data suggest that Ca2+ uptake into renal cortical
      ER is stimulated acutely during compensatory renal growth, perhaps through
      protein kinase C, and is stimulated chronically by parathyroid hormone.

PMID- 1393778
TI  - Kinetics of beta-glycerophosphate-induced endochondral mineralization in vitro.
      Calcium accumulation, alkaline phosphatase activity, and effects of levamisole.
AB  - Isolated mesenchymal limb bud cells from day-12 mouse embryos grown at high
      density in organoid culture at the medium/air interphase differentiate into
      chondrocytes and form cartilage nodules. Upon addition of beta-glycerophosphate
      (beta-GP), cartilage undergoes endochondral mineralization. This beta-GP-induced
      mineralization was investigated by measuring the calcium content in the cultures
      and the activity of alkaline phosphatase (AP) in the cell mass and the medium.
      Calcium incorporation depended on the amount of beta-GP added. After continuous
      treatment, mineralization began on day 8 of the culture period and increased
      linearly until day 15. In long-term cultures, periodical treatment for 6 days
      caused an increase in mineralization the older the cultures were, but the slope
      of increase was proportionately less steep. Treatment at the latest period on
      days 19-24 resulted in a markedly reduced mineralization. After short-term
      treatment (48 hours), mineralization increased also the older the cultures were
      and proceeded during further cultivation in beta-GP-free medium. This kinetic
      behavior indicates a dependency of mineralization on cartilage maturation in this
      in vitro system. AP activity increased enormously and nearly logarithmically in
      the cell mass in beta-GP-free medium, whereas beta-GP treatment inhibited this
      drastic increase. In the medium, considerable activities of AP were also
      measurable from day 10 onward. It increased in beta-GP-free medium up to day 14,
      but was diminished after mineralization had been induced. Levamisole inhibited AP
      activity dose dependently when added directly to the enzyme-containing medium
      (100% inhibition at 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393779
TI  - Alkaline phosphatase and peptidase levels in invertebrate cartilage.
AB  - Cartilage is encountered in the skeletons of many advanced invertebrates, yet it
      never calcifies or is replaced by bone. In an attempt to account for the absence
      of bone in invertebrates, we tested a hypothesis proposing that absence or
      inadequate quantities of several enzymes associated with vertebrate osteogenesis
      may underlie the failure of the invertebrates to evolve bone. The enzymes
      examined were alkaline phosphatase, alanyl beta-naphthylamidase, and neutral
      protease. Their activities were measured in the gill cartilage of the Atlantic
      horseshoe crab, Limulus polyphemus, and the odontophore cartilage of the marine
      whelk, Busycon canaliculatum. Animals were collected from the Cape Cod area.
      Samples of cartilage of Limulus perichondrium, various non-skeletal tissues, and
      neonatal rat calvaria, the latter as a reference standard, were homogenized in
      0.1 M phosphate buffer (pH 7.1) and analyzed for protein content and the above
      mentioned enzyme activities. Alkaline phosphatase specific activity was readily
      detected in most tissues except the invertebrate cartilage specimens in which it
      was present only at near-trace levels. Naphthylamidase and protease activities
      were present in all tissues. In a single experiment, higher phosphatase values
      were recorded for Limulus cartilage retaining perichondrium, but in a subsequent
      trial assaying cartilage retaining perichondrium, denuded cartilage, and isolated
      perichondrium separately, it was demonstrated that phosphatase activity resided
      primarily within the perichondrium. Exposure of thick cryostat sections to p
      nitrophenyl phosphate confirmed the suspicion that alkaline phosphatase activity
      was present principally in the perichondrium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1393777
TI  - Osteoclast precursors circulate in avian blood.
AB  - The osteoclast is known to be derived from a marrow-residing precursor that is a
      member of the mononuclear phagocyte family, but the means by which this cell
      moves from marrow to bone is unknown. We herein demonstrate that mononuclear
      progenitors capable of differentiating, in vitro, into cells exhibiting the
      osteoclast phenotype circulate in chickens. The mononuclear fraction was isolated
      on a density gradient from blood drawn from calcium-deprived laying hens and the
      plastic-adherent population was obtained. These cells are members of the
      mononuclear phagocyte family, as demonstrated by nonspecific esterase and
      tartrate-resistant acid phosphatase (TRAP) activities, expression of the
      macrophage-specific mannose receptor, and their ability to phagocytose latex
      particles. When cultured in the presence of devitalized bone, these cells undergo
      progressive multinucleation and ultimately become essentially indistinguishable
      from isolated osteoclasts and those generated from bone marrow precursors.
      Specifically, the blood-derived polykaryons are TRAP-positive, exhibit
      characteristic ruffled membranes, and express the osteoclast antigens 121F and
      23C6. When placed on bone slices, these cells form typical resorptive "pits."
      Moreover, when cultured with 3H-proline-labeled bone, the blood monocyte
      generated osteoclasts mobilize matrix as effectively as those derived from
      marrow. Thus, osteoclast precursors circulate in the blood of laying hens and can
      be induced to differentiate in vitro.

PMID- 1393780
TI  - Determination of histamine and polyamines in calcified tissues of mice:
      contribution of mast cells and histidine decarboxylase to the amount of histamine
      in the bone.
AB  - A simple method for determining histamine and polyamines in various tissues was
      devised. The method, however, could not be applied to calcified tissues, because
      the high concentration of Ca2+ in the extract interferes with the chromatographic
      separation of these amines. By treating the extracts from calcified tissues with
      K2CO3, we succeeded in removing the Ca2+, and the method could then be applied to
      determine the amines in bone tissues of mice. By using this method, we examined
      the contribution of mast cells and histidine decarboxylase (HDC) to the amount of
      histamine in the bone. The results indicate that (1) the HDC activity in the bone
      is the highest among the tissues of normal mice, and the histamine produced by
      the HDC in the bone is metabolized rapidly; (2) a major part of HDC in the bone
      is present in the bone marrow cells other than mast cells, and most of histamine
      in the bone is attributable to the histamine pooled in mast cells; (3) mast cells
      in the diaphysis are located largely along the endosteal lining; and (4) the
      method devised in this study may be useful for studying the roles of histamine
      (or mast cells) and polyamines in calcified tissues.

PMID- 1393781
TI  - An FT-IR microscopic investigation of the effects of tissue preservation on bone.
AB  - Fourier transform infrared microscopy is a powerful tool for the characterization
      of mineral and protein in histologic sections of bone. This study was concerned
      with determining whether techniques used to preserve these tissues and to prepare
      them for sectioning had an effect on spectral properties. The nu 1, nu 3
      phosphate bands in the 900-1200 cm-1 spectral region were used to evaluate the
      structure of the apatitic mineral in fresh-frozen, ethanol-fixed, and formalin
      fixed 35-day-old rat femurs; fresh-frozen and formalin-fixed 20-day-old fetal rat
      femurs; ground 35-day-old rat diaphyseal bone samples; and formalin-fixed,
      methacrylate-embedded ground diaphyseal bone. The crystallinity (crystal size and
      perfection) of the bone apatite was assessed by a curve-fitting analysis of the
      nu 1, nu 3 phosphate bands. Results indicate that ethanol or formalin fixation of
      the 35-day-old intact rat femur, and formalin fixation and embedding of the
      ground rat bone do not significantly alter the crystallinity of the apatite.
      However, formalin fixation of the fetal rat bone did alter the structure of the
      apatite mineral phase. In addition, evaluation of protein secondary structure in
      the 35-day-old rat femur from the Amide I and Amide II vibrations near 1650 and
      1550 cm-1, respectively, revealed that protein conformation was altered by
      ethanol fixation.

PMID- 1393782
TI  - Calcium biomineralization in the radular teeth of the chiton, Acanthopleura
      hirtosa.
AB  - A method has been devised for isolating the calcium biomineral from the iron
      biominerals and organic components present in the major lateral teeth of the
      chiton Acanthopleura hirtosa. Fourier-transform infrared spectroscopy of the
      calcium biomineral indicated that it was an apatite material containing carbonate
      and fluoride ions. Carbonate was not found to be present as a separate phase. The
      apatite was further separated into low and high density fractions, both of which
      showed crystallinity intermediate between that of bovine tibia cortical bone and
      human tooth enamel, as indicated by powder X-ray diffraction analysis. The
      calcified region of the major lateral teeth was also studied in situ using
      transmission electron microscopy and electron diffraction analysis, revealing a
      close spatial relationship between the mineral apatite phase and underlying
      organic matrix. It is suggested that the architectural arrangement of apatite
      biomineral and fibrous organic constituents imparts specialized mechanical
      properties to the tooth making it ideally suited for the task of obtaining food
      from hard surfaces.

PMID- 1393785
TI  - "Quo vadis, infection control?".

PMID- 1393783
TI  - CT image analysis of the vertebral trabecular network in vivo.
AB  - A method of computed tomography (CT) image analysis of lumbar vertebrae has been
      developed, providing a visualization of the trabecular network as it is
      represented in a 1.5 mm-thick CT image. We measured the length of the network and
      the number of discontinuities found in the image. The ratio of these measurements
      was called the "trabecular fragmentation index" (TFI). CT images from 71 women
      between the ages of 50 and 59, and 94 women between the ages of 60 and 69 were
      divided into three groups according to quantitative computed tomography (QCT)
      vertebral density and to the presence or absence of crushing and fractures. The
      measure of the network length versus the vertebral area was significantly higher
      in normal subjects than in osteoporotics. A TFI threshold at 0.195 could separate
      the normal subjects, regardless of the decade, from osteoporotic ones. In females
      between 50 and 69 years of age, TFI was 0.166 (SD = 0.031) for the normal group
      and 0.248 (SD = 0.082) for osteoporotics. The osteopenic group without fractures
      but low bone mineral density (BMD) showed an intermediate TFI of 0.195 (SD =
      0.05), placing this population on both sides of the threshold. Correlation
      between TFI and BMD was only -0.60. TFI could provide new information in vivo
      about the state of trabecular structure, particularly in the osteopenic group.

PMID- 1393786
TI  - The future is now.

PMID- 1393784
TI  - Soft tissue calcification induced by iron complexes.
AB  - Complexed iron (III) induces a local calcification of soft tissues in mice that
      is strongly dependent upon the nature of the complexing molecule. Ferric lactate
      is much more effective in inducing calcification than iron dextran.

PMID- 1393787
TI  - Hepatitis B.

PMID- 1393788
TI  - Infection control.

PMID- 1393789
TI  - Infection control.

PMID- 1393790
TI  - Fluorosis.

PMID- 1393791
TI  - CDA--1902-1992--90 years of leadership.

PMID- 1393792
TI  - Hiring the best and the brightest.
AB  - Successful dentistry in the nineties demands a well-trained staff who are
      effective decision makers, team players and committed to excellence. The key to
      fulfilling this order begins with you, the dentist. It is incumbent on you to
      invest serious time and thought into the selection of staff. If you do so, you'll
      likely be surrounded by people who will turn your vision into reality. If you
      don't, you'll be caught in a staffing quagmire, and your practice vision will
      remain all-elusive.

PMID- 1393793
TI  - Who's got the patient? The pitfalls of working with another dentist.

PMID- 1393794
TI  - Bonded silver amalgam restorations.

PMID- 1393795
TI  - Esthetic alternatives for posterior teeth: porcelain and laboratory-processed
      composite resins.
AB  - Porcelain and laboratory-processed composite inlays and onlays are enjoying
      increasing popularity as a result of heightened patient concern over the
      esthetics and biocompatibility of restorative materials. This paper reviews
      current clinical concerns about porcelain and indirect composite restorations,
      focusing on indirect procedures, microleakage, technique sensitivity, long-term
      serviceability, finish and polish, abrasion, and wear resistance. The available
      data indicate that there are still significant limitations to the routine use of
      these esthetic alternatives for posterior restorations.

PMID- 1393796
TI  - A critical view of the rationale for routine, initial and periodic radiographic
      surveys.
AB  - Most dentists and dental faculties use an initial radiographic survey for the
      comprehensive-care patient rather than selective radiography, as recommended by
      professional organizations and radiation protection agencies. Survey or screening
      radiography has been justified in the belief that it is an essential health
      service designed to disclose serious occult disease and that failure to use such
      films might expose the dentist to successful malpractice litigation. However,
      incidence data indicate the chance of disclosing tumors, non-inflammatory cysts
      or other serious bone disease in the asymptomatic patient by screening jaw films
      is infinitesimal. On this basis, the practice is not justifiable as a public
      health measure, nor is the dentist who follows published national guidelines for
      prescription radiography vulnerable to successful litigation.

PMID- 1393797
TI  - Dental management of anticoagulated patients.
AB  - Today's trend toward ambulatory medical care will bring more pharmacological
      problems into the dental office. While the dental management of patients taking
      oral anticoagulants is controversial, current research supports the contention
      that they can be safely treated on an outpatient basis. The use of the
      International Normalized Ratio (INR) has made better estimates of prothrombin
      time possible, and patients can be maintained in a narrow therapeutic range.
      Postoperative hemorrhage can be avoided or controlled with local hemostatic
      agents.

PMID- 1393798
TI  - [Risks and benefits of extraction of impacted third molars: A critical review of
      the literature. 2].
AB  - In part I of this critical review of the literature on the risks and benefits of
      removing impacted third molars, we have dealt with: I--Risks of non-intervention.
      This second part is about: II--Risks of intervention, III--Benefits of non
      intervention, and, finally, IV--Benefits of intervention.

PMID- 1393799
TI  - Statistical software definitions to assist the student in understanding available
      commands.

PMID- 1393800
TI  - Computer-based patient record: from pipe dream to reality.

PMID- 1393801
TI  - Implementation of a computerized information system in a long-term care facility.
AB  - The successful implementation of computerized nursing information systems
      requires the completion of many tasks and the participation of many persons. In
      1989, Pulliam and Boettcher described a six-step process for introducing
      computerized information systems into long-term care facilities. This article
      describes the process, particularly the implementation phase, as it actually
      happened in a 124-bed facility in a mid-Atlantic state. This facility found that
      successful implementation requires a systems coordinator who is a professional
      nurse who understands the needs of the patients, can integrate information with
      the computer system, and can provide on-going support for the users.

PMID- 1393803
TI  - A dynamic test system: its development and implementation.
AB  - A dynamic test system that uses a computer, commercially available software [Data
      Base IV], and logical human thinking was designed. The system facilitates
      construction of a multiple-choice test, places an emphasis on the use of item
      analysis statistics, and establishes a feedback mechanism for faculty to use when
      preparing a multiple-choice examination. Prerequisites to the system, development
      of the system, test construction, and outcomes are described.

PMID- 1393802
TI  - Computer assisted instruction for preoperative and postoperative patient
      education in joint replacement surgery.
AB  - This article describes a comprehensive system for preoperative and postoperative
      patient education. The system offers a cost-effective method of instruction which
      encourages patient interaction and practice with decision making. The system was
      designed for patients undergoing total joint replacement surgery and includes two
      preoperative lessons, and a third lesson presented postoperatively at the
      bedside. The computer lessons were developed using data collected by a patient
      assessment instrument, and collaboratively with input from a nurse clinical
      specialist, orthopedic surgeon, physical therapist, and computer programmer. In
      this project, several advantages for using computer assisted instruction for
      preoperative and postoperative patient education were identified.

PMID- 1393804
TI  - The integration of theoretical constructs into the design of computer assisted
      instruction.
AB  - The authors believe that for computer assisted instruction to be an effective
      instructional tool, it must incorporate the most current theoretical principles
      related to learning and instruction. To assist future developers of computer
      assisted instruction, the authors review some of the major constructs from the
      theoretical foundations of various disciplines and then illustrate the
      integration of these constructs in the design of a software program entitled SOS-
      Strategies for Problem Solving.

PMID- 1393805
TI  - Evaluation of corneal topography: past, present and future trends.
AB  - The keratometer and photokeratoscope have long been the standard instruments for
      measuring corneal curvature. The recent development of computer-assisted
      photokeratoscopy has greatly enhanced the evaluation of corneal topography,
      helping improve our understanding of both normal and abnormal topography and
      their influence on visual acuity. The authors review normal corneal topography
      and compare various tools, both new and old, currently available for evaluating
      corneal contour. Case studies are presented to illustrate some of the clinical
      and research applications of computer-assisted photokeratoscopy in an
      ophthalmology practice. Future applications of computer-assisted photokeratoscopy
      include intraoperative topography, the design of custom-fitted contact lenses and
      combination with ray-tracing analysis.

PMID- 1393806
TI  - Eye injuries in Canadian sports and recreational activities.
AB  - Over 4000 eye injuries, including 449 blind eyes, have been reported in sports
      and recreational activities in Canada over the past 20 years. This is not only a
      great personal loss but also a financial loss, both to the injured person and to
      the community. Statistics should be tabulated on catastrophic injuries that leave
      the person with a physical or mental deficit, such as a blind eye, and efforts
      should be directed toward preventing such injuries. Changing and enforcing game
      rules and providing proper eye protection has proved very beneficial in Canadian
      hockey, racket sports and war games. Educational programs supported by the media
      and government that alert players to the need for eye protection are required.
      Such measures may lead to the prevention of up to 90% of injuries in sports and
      recreational activities in Canada.

PMID- 1393807
TI  - Effect of combined peribulbar and retrobulbar injection of large volumes of
      anesthetic agents on the intraocular pressure.
AB  - A prospective randomized study was done in 79 patients undergoing elective
      routine cataract surgery in which the Kelman phacoemulsification technique was
      used with placement of an intraocular lens. In all the patients anesthesia was
      induced with both a peribulbar and a retrobulbar injection of a large volume
      (total 10.5 mL) of local anesthetic. The patients were randomly assigned to
      receive either the peribulbar (39 patients) (group 1) or the retrobulbar (40
      patients) (group 2) injection first. The intraocular pressure (IOP) was measured
      five times during anesthesia. The mean elevation in IOP immediately after the
      first injection was 0.4 mm Hg in group 1, compared with 2.0 mm Hg in group 2.
      Twenty minutes after both injections had been given and a Super Pinky pressure
      device had been placed on the eye, the mean decrease in IOP from the preoperative
      value was 3.1 mm Hg in group 1 and 4.8 mm Hg in group 2. We conclude that a
      combined peribulbar and retrobulbar approach is a safe and effective alternative
      method of regional anesthesia for cataract surgery.

PMID- 1393808
TI  - Treatment of encapsulated blebs with 30-gauge needling and injection of low-dose
      5-fluorouracil.
AB  - We describe a simplified needling procedure, performed at the slit-lamp, with
      injection of low-dose 5-fluorouracil to treat encapsulated filtering blebs.
      Between August 1989 and December 1990 we treated 17 eyes of 14 patients with this
      procedure. At 2 months 13 of the eyes had needed only one needling procedure.
      Risk factors for reencapsulation of the bleb were a history of three or more
      previous surgical procedures (p less than 0.05) and prolonged preoperative use of
      topical adrenergic drugs (p less than 0.05). At 1 year all but one eye had an
      intraocular pressure below 21 mm Hg (median 15 mm Hg). Twelve of the eyes had
      needed more than one needling procedure. There were no serious complications of
      the 32 procedures performed. The incidence rate of minor complications (wound
      leaks, corneal erosion and small hyphemas) was 38%.

PMID- 1393809
TI  - Long-term course of antimalarial maculopathy after cessation of treatment.
AB  - Since 1980 I have examined some 1650 patients for the presence or absence of
      antimalarial maculopathy. Bilateral, irreversible visual field defects have been
      diagnosed is 62 patients, 37 of whom have been followed for at least 4 years. The
      22 patients who presented with relative scotomas did not lose central visual
      acuity; over a median follow-up period of 6.0 years 33 (75%) of the eyes
      maintained their visual field, 5 (11%) showed some improvement in visual field, 4
      (9%) lost some visual field, and 2 (4%) manifested small absolute scotomas. Nine
      (60%) of the 15 patients who presented with absolute scotomas were symptomatic.
      Over a median follow-up period of 8.8 years 19 (63%) of the eyes in this group
      lost one or more lines of visual acuity, including 4 (13%) that became legally
      blind; 19 (63%) lost field owing to an increase in the size of the absolute
      scotomas (13 eyes) or the development of new absolute scotomas (6 eyes). The
      results suggest that the visual prognosis is excellent if antimalarial therapy is
      stopped at an early stage of the disease.

PMID- 1393810
TI  - Comparison of threshold and standard Amsler grid testing in patients with
      established antimalarial retinopathy.
AB  - To evaluate the sensitivity of threshold Amsler grid testing in the detection of
      established antimalarial retinopathy, 30 eyes of 15 patients with bilateral,
      irreversible field defects were examined with the standard Amsler grid and the
      threshold Amsler grid. Four eyes (13%) showed significant enlargement of large
      relative scotomas on testing with the threshold Amsler grid. Although only a
      small proportion of the eyes demonstrated an increase in the size of the scotoma,
      the patients had established field defects of varying depth, in some cases
      absolute scotomas. A prospective study in patients with early disease (i.e., with
      small, shallow scotomas) may be worth while.

PMID- 1393811
TI  - Dye yellow vs. argon green laser in panretinal photocoagulation for proliferative
      diabetic retinopathy: a comparison of minimum power requirements.
AB  - We compared the power required to achieve a retinal burn with the dye yellow
      laser (wavelength 577 nm) and the argon green laser (wavelength 514 nm) in 49
      eyes of 38 patients with proliferative diabetic retinopathy who underwent
      panretinal photocoagulation. All eyes were treated with both lasers. The dye
      laser required on average 35.7% less power to achieve a retinal burn than the
      argon laser (p = 0.0001). With both lasers more power was needed in patients
      older than 55 years than in those aged 55 years or less and in patients with
      light skin versus those with dark skin (p less than 0.02). The lower power
      required with the dye yellow laser allows facilitated photocoagulation in
      patients in whom treatment with the argon green laser would be problematic.

PMID- 1393812
TI  - Choroidal detachment associated with retinal detachment as a presenting finding.
AB  - Choroidal detachment along with retinal detachment as a presenting finding is
      rare. We identified five such cases presenting to our ophthalmology practice
      between 1964 and 1991. The patient is usually myopic and presents with marked
      visual loss, profound hypotony and a marked anterior chamber reaction. The
      pathogenesis seems to revolve around the hypotony and myopia and an unstable
      choroidal vascular system. Management usually involves a scleral buckling
      procedure with cryotherapy under direct visualization to release choroidal and
      subretinal fluid, possibly preceded by a few days of anti-inflammatory therapy.
      The overall prognosis is poor owing to delays in diagnosis and the postoperative
      development of proliferative vitreoretinopathy.

PMID- 1393814
TI  - Favourable outcome in a patient with penetrating intraocular BB pellet injury.
AB  - Intraocular BB pellet injuries are a devastating form of ocular trauma with a
      poor prognosis. The penetration of the eye by the pellet causes a marked
      disruption of the intraocular contents that in most cases leads to enucleation.
      We describe a 15-year-old boy who suffered a penetrating intraocular BB pellet
      injury to his right eye and underwent primary repair of the injury followed by
      secondary vitrectomy and prophylactic panretinal photocoagulation. The
      postoperative management was complicated by a retinal detachment; however, this
      responded to a scleral buckling procedure. Eighteen months after the injury the
      acuity in the affected eye was 20/30 with a contact lens. To our knowledge this
      is the first case in which useful vision has been recovered in this type of
      injury.

PMID- 1393813
TI  - Late-onset Moraxella catarrhalis endophthalmitis after filtering surgery.
AB  - We describe a young man in whom endophthalmitis caused by Moraxella catarrhalis
      developed 5 years after glaucoma filtering surgery. The infection responded to
      treatment with broad-spectrum antibiotics, and 2 months after presentation the
      visual acuity had returned to 20/50. To our knowledge this is the first report of
      late-onset endophthalmitis due to M. catarrhalis complicating glaucoma filtering
      surgery.

PMID- 1393815
TI  - Symposium on ultraviolet radiation-related diseases: a risk management approach.

PMID- 1393816
TI  - Clinical trials: where do we go from here?

PMID- 1393817
TI  - Relative persistence capacity of BCG substrains in mouse spleen. Computerized
      statistical analysis. Multiple comparison.
AB  - The relative persistence capacity in mouse spleen of 10 and 9 BCG substrains from
      liquid and dried vaccines, respectively, was evaluated in two studies.
      Recoverable BCG colony counts from mouse spleen were determined at given days on
      solid medium in the two studies during a period of 1-360 and 1-345 days,
      respectively, after the intravenous BCG vaccination, performed with two different
      viable units. From 36,000 (study 1) and 21,600 (study 2) recoverable BCG colony
      counts, 180 and 108 mean relative persistence capacity values were estimated to
      test the residual virulence during the follow-up time, using computerized
      statistical analysis. The early and late trends of mean relative persistence
      capacity of the BCG substrains in mouse spleen were tested by linear regression
      analysis and analysis of variance and covariance; then with ranked adjusted group
      mean relative persistence capacity, Gabriel's simultaneous test procedure was
      performed for multiple comparison to diminish type 1 error in statistical
      inference and in objective interpretation of the experimental results. The
      associations of the ranked mean relative persistence capacity of the BCG
      substrains at the different sacrifice days of mice were also analyzed by
      Kendall's test of concordance. The early, late, and overall relative persistence
      capacity reflects the residual virulence of the BCG substrains and provides
      information on the required protective efficacy (immunogenicity) and adverse
      reactions (reactogenicity), allowing the appropriate vaccination dose, expressed
      in viable units of the substrain used, to be determined.

PMID- 1393818
TI  - Cooperation between two Thiobacillus strains for heavy-metal removal from
      municipal sludge.
AB  - A mixed culture of two fast-growing bacterial strains for heavy-metal
      solubilization of municipal sewage sludge has been developed. Strain VA-7
      decreases the initial sludge pH (7-8.5) to a value between 4.0 and 4.5. Then,
      strain VA-4 begins growing and further reduces the pH to values below 2.0. The
      rapid decrease of sludge pH by a mixed culture through sulfur oxidation into
      sulfuric acid solubilizes the toxic metals (Cd 83-96%, Cr 16-54%, Cu 85-87%, Mn
      91-94%, Ni 78-79%, Pb 28-46%, Zn 82-96%) to levels recommended for intensive use
      of residual sludge in agriculture. A study of the physiological and metabolic
      characteristics of these strains revealed that isolate VA-7 is a strain of
      Thiobacillus thioparus (ATCC 55127), while isolate VA-4 corresponds to a
      Thiobacillus thiooxidans (ATCC 55128). These bacterial strains possess
      distinctive physiological characteristics that allow them to easily grow and
      solubilize heavy metals in municipal sludge.

PMID- 1393819
TI  - Modulation of murine macrophage responses stimulated with influenza
      glycoproteins.
AB  - Previously it was reported that influenza virus stimulated, nonspecific
      resistance was largely due to its glycoproteins, hemagglutinin (HA) and
      neuraminidase (NA). The enhancement of natural killer cell activity was the
      intrinsic property of NA and HA. In the present study, the stimulatory effect of
      these glycoproteins on the murine peritoneal macrophages was studied.
      Electrophoretically purified glycoproteins, NA and HA, of influenza virus
      A/USSR/90/77 (H1N1) were administered intraperitoneally to C3H/HeN mice, with or
      without stearyl tyrosine (ST). Macrophages were isolated and were restimulated
      with phorbol myristate acetate. H2O2 secretion was determined by horseradish
      peroxidase dependent oxidation of phenol red assay. HA enhanced H2O2 secretion
      only in the presence of ST (60 nmol.mg-1.h-1), whereas NA alone stimulated H2O2
      secretion (83 nmol.mg-1.h-1), by 6-fold over control (13 nmol.mg-1.h-1), and this
      stimulation was further increased (136 nmol.mg-1.h-1) in the presence of ST.
      Interleukin 1 (IL-1) activity was determined by using D10.G4.1 cells. There was a
      little stimulation of IL-1 activity (less than 1 U/mL) of macrophages isolated
      from HA-primed of HA+ST-primed mice restimulated with HA. On the other hand, IL-1
      activity of macrophages isolated from NA-primed mice restimulated with NA
      significantly increased (102 U/mL) over control (less than 1 U/mL), and an
      additional 2-fold increase (231 U/mL) resulted when macrophages from NA+ST-primed
      mice were used. Tumor necrosis factor (TNF) activity was examined by using L929
      cells. Negligible TNF activity was observed in macrophages isolated from either
      HA-primed or HA+ST-primed mice restimulated with HA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1393820
TI  - Nucleotide sequence analysis of the gene encoding the Caulobacter crescentus
      paracrystalline surface layer protein.
AB  - The entire nucleotide sequence of the rsaA gene, encoding the paracrystalline
      surface (S) layer protein (RsaA) of Caulobacter crescentus CB15A, was determined.
      The rsaA gene encoded a protein of 1026 amino acids, with a predicted molecular
      weight of 98,132. Protease cleavage of mature RsaA protein and amino acid
      sequencing of retrievable peptides yielded two peptides: one aligned with a
      region approximately two-thirds the way into the predicted amino acid sequence
      and the second peptide corresponded to the predicted carboxy terminus. Thus, no
      cleavage processing of the carboxy portion of the RsaA protein occurred during
      export, and with the exception of the removal of the initial methionine residue,
      the protein was not processed by cleavage to produce the mature protein. The
      predicted RsaA amino acid profile was unusual, with small neutral residues
      predominating. Excepting aspartate, charged amino acids were in relatively low
      proportion, resulting in an especially acidic protein, with a predicted pI of
      3.46. As with most other sequenced S-layer proteins, RsaA contained no cysteine
      residues. A homology scan of the Swiss Protein Bank 17 produced no close matches
      to the predicted RsaA sequence. However, RsaA protein shared measurable homology
      with some exported proteins of other bacteria, including the hemolysins. Of
      particular interest was a specific region of the RsaA protein that was homologous
      to the repeat regions of glycine and aspartate residues found in several
      proteases and hemolysins. These repeats are implicated in the binding of calcium
      for proper structure and biological activity of these proteins. Those present in
      the RsaA protein may perform a similar function, since S-layer assembly and
      surface attachment requires calcium. RsaA protein also shared some homology with
      10 other S-layer proteins, with the Campylobacter fetus S-layer protein scoring
      highest.

PMID- 1393821
TI  - Biodegradation of soil humic acids by Streptomyces viridosporus.
AB  - Biodegradation of soil humic acids by Streptomyces viridosporus ATCC 39115
      growing in a mineral salts--glucose medium was demonstrated. This biodegradation
      accompanies bacterial growth and is, therefore, presumed to be a primary
      metabolic activity, but humic acids were not used as the sole source of carbon.
      This bacterial activity was enhanced when cells were shaken and within a pH range
      of 6.5-8.5. In further experiments, the relative abilities of S. viridosporus to
      mineralized [14C]melanoidin, used as synthetic humic acid, were also established.
      In contrast to the white rot fungus Phanerochaete chrysosporium, another
      microorganism exhibiting humic acid degrading activity at acidic pH, poor
      extracellular activities were found in culture medium of S. viridosporus, and
      veratryl alcohol does not result in increased humic acid degradation. In spite of
      some peroxidase activity measured in culture filtrates and analyzed by
      polyacrylamide gel electrophoresis, the humic acid degrading system of S.
      viridosporus, in these experimental conditions, seems to be cell associated.

PMID- 1393822
TI  - Fonsecaea pedrosoi: lipid composition and determination of susceptibility to
      amphotericin B.
AB  - Conidia and mycelial cells of Fonsecaea pedrosoi ATCC 46428 were obtained for
      analyses of lipid composition. Total lipids, phospholipids, sterols, and
      qualitative sterols and fatty acid composition were determined. A higher lipid
      content was detected in conidia than in mycelial cells of Fonsecaea pedrosoi,
      which could not be attributed to total sterols and phospholipids. In both forms
      of this fungus, ergosterol was the only sterol detected. The minimal inhibitory
      concentration of amphotericin B was lower for conidia than for mycelium.

PMID- 1393823
TI  - Cloning of tetracycline-resistance genes from various strains of Clostridium
      perfringens and expression in Escherichia coli.
AB  - One hundred strains of Clostridium perfringens and 52 strains of other clostridia
      of human and animal origins were screened for tetracycline resistance. Fifty-six
      strains were resistant to tetracycline in the C. perfringens group. Ten strains
      were selected for their high level of resistance. In all of them, the
      tetracycline-resistance genes were found to be residing in large plasmids of
      about 50 kb, all showing homologies. Several tetracycline-resistance genes from
      plasmids of various strains of C. perfringens were cloned in plasmid pUC19 and
      the resistance was expressed in Escherichia coli. Hybridization analysis showed
      these genes to be homologous among themselves and also to tetP gene from the PCW3
      type plasmid.

PMID- 1393824
TI  - Microcarrier culture of fish cells and viruses in cell culture bioreactor.
AB  - This article deals with the culture of grass carp (Ctenopharyngodon idellus) lip
      and embryo cells on Cytodex 3 and GT-2 microcarriers in a 1.5-L cell culture
      bioreactor to propagate grass carp hemorrhage virus. The cells and viruses were
      successfully cultivated at 26 degrees C, pH 7.0, and dissolved oxygen 40% of air
      saturation. The cell density achieved was as high as 7.4 x 10(6) cells/mL, and
      the virus titre reached 6.75 log LD50/0.5 mL from an initial 3.00 log LD50/0.5
      mL. The results present broad prospects for fish virus vaccine production.

PMID- 1393825
TI  - Recovery of Bacteroides fragilis group from clinical specimens following
      antimicrobial therapy.
AB  - Over a period of 14 years (1973-1987), 3165 specimens submitted to the
      microbiology laboratory demonstrated the recovery of anaerobic bacteria. A total
      of 988 Bacteroides fragilis group isolates were recovered (0.3 isolates per
      specimen). Bacteroides fragilis accounted for 62% of the total of all B. fragilis
      group isolates, Bacteroides thetaiotaomicron for 15%, Bacteroides vulgatus for
      8%, Bacteroides ovatus for 7%, Bacteroides distasonis for 6%, and Bacteroides
      uniformis for 2%. Of the 988 B. fragilis group isolates, 310 (31%) were recovered
      after the administration of antimicrobial therapy, and 129 (13%) were the single
      isolate recovered from the infected site at that time. The recovery rate of all
      members of B. fragilis group after the administration of antimicrobial therapy,
      when isolated alone or when mixed with other bacteria, was similar. The data
      illustrate the equal ability of all members of the B. fragilis group to persist
      in and to contribute to the inflammatory process; and provide further support for
      their pathogenic role.

PMID- 1393826
TI  - A succinate transport mutant of Bradyrhizobium japonicum forms ineffective
      nodules on soybeans.
AB  - Biochemical evidence has shown that dicarboxylic acids actively support symbiotic
      nitrogen fixation by both fast- and slow-growing Rhizobium. Mutants defective in
      the active uptake of succinate have been previously described only in species of
      the fast-growing rhizobium. This article is a report on the isolation of mutants
      defective in dicarboxylate transport in a slow-growing species of rhizobium,
      Bradyrhizobium japonicum. One of these presumptive dicarboxylate transport
      mutants, GTS, was characterized further. Cultured GTS was unable to accumulate
      [14C]succinate above background levels but possessed normal rates of malate
      dehydrogenase, fumarase, and hydroxybutyrate dehydrogenase activities. When
      inoculated onto soybeans, GTS produced a Nod+, Fix- phenotype. The bacteroids
      isolated from these nodules failed to accumulate labelled succinate. Electron
      micrographs of nodules formed by inoculation with GTS appeared normal with the
      exceptions of more prominent peribacteroid spaces in the infected cells and the
      appearance of starch granules in the noninfected cells. The phenotypical and
      morphological changes observed for B. japonicum are similar to those previously
      reported for the fast-growing species.

PMID- 1393827
TI  - Biochemical characterization and time-course analysis of Lymantria dispar nuclear
      polyhedrosis virus with monoclonal antibodies.
AB  - Hybridoma cell lines secreting monoclonal antibodies (MAbs) specific to a 31,000
      molecular weight viral protein or a 31,000 molecular weight polyhedrin protein of
      Lymantria dispar nuclear polyhedrosis virus (LdNPV) were developed. The two
      polypeptides were shown to be different by comparing their amino acid
      compositions. Immuno-electron microscopy was used to verify specific binding of
      the MAbs to their respective targets. Specific MAbs were used to develop an ELISA
      procedure to monitor the development of LdNPV virus and polyhedrin in vivo.
      Results indicated that in hemolymph of larvae fed 10(6) polyhedral inclusion
      bodies, the concentration of virus began to increase 16 h after inoculation and
      continued to increase for the next 5 days. By 36 h, the concentration of
      polyhedrin increased and was maintained at a high level in the later stages of
      infection. One-third of this group of infected larvae survived the infection. In
      these individuals, the concentrations of virus and polyhedrin declined to a low
      level 5 days after infection. This suggests the presence of a host mechanism for
      clearing the virus from the hemolymph.

PMID- 1393828
TI  - Effect of nitrogen sources on oxidoreductive enzymes and ethanol production
      during D-xylose fermentation by Candida shehatae.
AB  - The effect on D-xylose utilization and the corresponding xylitol and ethanol
      production by Candida shehatae (ATCC 22984) were examined with different nitrogen
      sources. These included organic (urea, asparagine, and peptone) and inorganic
      (ammonium chloride, ammonium nitrate, ammonium sulphate, and potassium nitrate)
      sources. Candida shehatae did not grow on potassium nitrate. Improved ethanol
      production (Y(p/s), yield coefficient (grams product/grams substrate), 0.34) was
      observed when organic nitrogen sources were used. Correspondingly, the xylitol
      production was also higher with organic sources. Ammonium sulphate showed the
      highest ethanol:xylitol ratio (11.0) among all the nitrogen sources tested. The
      ratio of NADH- to NADPH-linked D-xylose reductase (EC 1.1.1.21) appeared to be
      rate limiting during ethanologenesis of D-xylose. The levels of xylitol
      dehydrogenase (EC 1.1.1.9) were also elevated in the presence of organic nitrogen
      sources. These results may be useful in the optimization of alcohol production by
      C. shehatae during continuous fermentation of D-xylose.

PMID- 1393829
TI  - Sheen formation and growth response of groundwater bacteria to reduced oxygen
      concentrations during incubation of M-Endo medium.
AB  - In vitro pure-culture studies were conducted to assess growth and sheen formation
      of groundwater bacteria on M-Endo medium incubated under reduced oxygen
      concentrations (0, 4, 8, 12, and 16%). Coliform and noncoliform bacteria were
      isolated from 17 untreated, rural groundwater supplies on M-Endo medium. All 16
      coliform isolates tested were capable of sheen formation at oxygen concentrations
      of 4% or greater, yet some of these same isolates (Enterobacter aerogenes,
      Enterobacter cloacae, and Hafnia alvei) were either unable to grow or failed to
      produce a metallic sheen when incubated under strict anaerobiosis. Approximately
      70% of the 21 noncoliform isolates examined exhibited growth inhibition at oxygen
      concentrations of 8% or less. The growth of a false-positive coliform isolate of
      Serratia fonticola was inhibited when incubated under reduced oxygen
      concentrations of 16% or less. Our findings suggest that the selectivity of M
      Endo medium, and resultant inhibition of noncoliforms and false-positive
      coliforms, is enhanced by incubation in the absence of oxygen. However, the
      failure of strict anaerobiosis to permit detection of total coliforms such as
      Hafnia and Enterobacter spp. may compromise the reliability of this technique for
      evaluating the sanitary quality of some waters. On the other hand, oxygen
      concentrations of 4, 8, 12, and 16% permitted adequate sheen development of all
      coliforms tested while inhibiting some noncoliforms.

PMID- 1393830
TI  - Binding of mutagenic pyrolyzates to fractions of intestinal bacterial cells.
AB  - The binding of mutagenic pyrolyzates to cell fractions from some gram-negative
      intestinal bacteria and to thermally treated bacterial cells was investigated. 3
      Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H
      pyrido[4,3-b]indole (Trp-P-2) were effectively bound by several of the bacterial
      cells. The cell wall skeletons of all bacteria effectively bound Trp-P-1 and Trp
      P-2. Their cytoplasmic fractions retained Trp-P-1 and Trp-P-2, but to a lesser
      extent than the cell wall skeletons. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ)
      was not found in their cytoplasmic fractions. These cell wall skeletons also
      bound 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-amino-5
      phenylpyridine (Phe-P-1), IQ, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ),
      and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQX). The amount of each
      mutagen bound differed with the type of mutagen and the bacterial strain used.
      The outer membrane of Escherichia coli IFO 14249 showed binding of about 123.7
      micrograms/mg of Trp-P-2, and its cytoplasmic membrane bound 57.14 micrograms/mg.
      Trp-P-2 bound to the bacterial cells was extracted with ammonia (5%), methanol,
      and ethanol but not with water.

PMID- 1393832
TI  - Relationship of low lysine and high arginine concentrations to efficient
      ethanolic fermentation of wheat mash.
AB  - Very high gravity wheat mashes containing 20 or more grams of carbohydrates per
      100 mL were fermented completely by Saccharomyces cerevisiae, even though these
      mashes contained low amounts of assimilable nitrogen. Supplementation of wheat
      mashes with various amino acids or with yeast extract, urea, or ammonium sulfate
      reduced the fermentation time. However, lysine or glycine added as single
      supplements, inhibited yeast growth and fermentation. With lysine, yeast growth
      was severely inhibited, and a loss of cell viability as high as 80% was seen.
      Partial or complete reversal of lysine-induced inhibition was achieved by the
      addition of a number of nitrogen sources. All nitrogen sources that relieved
      lysine-induced inhibition of yeast growth also promoted uptake of lysine and
      restored cell viability to the level observed in the control. They also increased
      the rate of fermentation. Experiments with minimal media showed that for lysine
      to be inhibitory to yeast growth, assimilable nitrogen in the medium must be in
      growth-limiting concentrations or totally absent. In the presence of excess
      nitrogen, lysine stimulated yeast growth and fermentation. Results indicate that
      supplementing wheat mash with other nitrogen sources increases the rate of
      fermentation not only by providing extra nitrogen but also by reducing or
      eliminating the inhibitory effect of lysine on yeast growth.

PMID- 1393831
TI  - Eradication of biofilm cells of Staphylococcus aureus with tobramycin and
      cephalexin.
AB  - The kinetics of growth and formation of biofilm by Staphylococcus aureus were
      investigated under iron-limited conditions in the chemostat. The population of
      planktonic cells reached 5.5 x 10(9) cells/mL 24 h after inoculation (D = 0.05 h
      1) and remained constant throughout. The number of biofilm cells of S. aureus
      colonizing the silicone tubing increased exponentially from 6 x 10(4) to 2.7 x
      10(7) cells/cm2 (6 days later) and continued to increase at a reduced rate to 2.7
      x 10(8) cells/cm2 on day 13. Planktonic cells of S. aureus were susceptible to
      tobramycin and cephalexin. The planktonic cells could be successfully eradicated
      with a combination of 5 micrograms tobramycin plus 100 micrograms cephalexin per
      millilitre. Exposure of young biofilm cells of S. aureus to 5 micrograms
      tobramycin plus 100 micrograms cephalexin per millilitre resulted in a rapid loss
      of cell viability. The percentage of survival dropped to less than 0.0001% after
      exposure to these concentrations of antibiotics for 3 h. Old biofilm cells of S.
      aureus were found to be extremely resistant to these antibiotics. The cell
      viability was reduced to 0.09% after exposure to 10 micrograms tobramycin plus
      100 micrograms cephalexin per millilitre. The results suggest that it is possible
      to eradicate S. aureus infection at the early stage with tobramycin plus
      cephalexin. Any delay in implementing antibiotic therapy is likely to result in
      the failure of the treatment. It is important to note that the concentrations of
      antibiotics required for the eradication of young biofilm cells must be
      determined for the treatment of device-associated infections.

PMID- 1393833
TI  - Bactericidal properties of peracetic acid and hydrogen peroxide, alone and in
      combination, and chlorine and formaldehyde against bacterial water strains.
AB  - The bactericidal properties of peracetic acid, hydrogen peroxide, chlorine, and
      formaldehyde were compared in vitro using a rapid micromethod. A combination of
      peracetic acid and hydrogen peroxide was also tested to assess interactions. The
      activities of these agents, which are widely used as disinfectants, were
      evaluated against water isolates and culture collection strains. Peracetic acid
      and chlorine exhibited an excellent antimicrobial activity, with a relatively
      rapid destruction of 10(5) bacteria/mL. The time-dependent bactericidal
      activities of hydrogen peroxide and formaldehyde were the lowest. The combination
      of peracetic acid and hydrogen peroxide, tested by a checkerboard micromethod,
      was found to be synergistic. The minimal bactericidal concentration was
      established in terms of time for a given mixture of peracetic acid and hydrogen
      peroxide. Determination of bactericidal concentrations showed that synergy was
      maintained with increasing contact time. Concentrations for minimal times of
      treatment by chemicals that provided interesting activities in vitro were tested
      for disinfection of ultrafiltration membranes. The bactericidal activities of
      peroxygen compounds were confirmed and synergism was maintained in working
      conditions. Chlorine showed a loss of efficacy when used on membranes.

PMID- 1393835
TI  - Serotyping of Bacillus thuringiensis environmental isolates by extracellular heat
      stable somatic antigens.
AB  - A total of 525 Bacillus thuringiensis environmental isolates, belonging to the
      five flagellar (H) serovars (alesti, sotto, kenyae, aizawai, and morrisoni), were
      serotyped by extracellular heat-stable somatic antigens (HSSAs). The isolates
      belonging to a given H serovar were assigned to a single HSSA serogroup at a high
      frequency, 87-100%. This indicates that the extent of HSSA variation within a
      single H serovar is small in the field populations of these B. thuringiensis
      serovars.

PMID- 1393834
TI  - Alcoholic glucose and xylose fermentations by the coculture process:
      compatibility and typing of associated strains.
AB  - As part of the simultaneous fermentation of both glucose and xylose to ethanol by
      a coculture process, compatibilities between xylose-fermenting yeasts and glucose
      fermenting species were investigated. Among the Saccharomyces species tested,
      none inhibited growth of the xylose-fermenting yeasts. By contrast, many xylose
      fermenting yeasts, among the 11 tested, exerted an inhibitory effect on growth of
      the selected Saccharomyces species. Killer character was demonstrated in three
      strains of Pichia stipitis. Such strains, despite their high fermentative
      performances, cannot be used to ferment D-xylose in association with the selected
      Saccharomyces species. From compatibility tests between xylose-fermenting yeasts
      and Saccharomyces species, pairs of microorganisms suitable for simultaneous
      xylose and glucose fermentations by coculture are proposed. Strains associated in
      the coculture process are distinguished by their resistance to mitochondrial
      inhibitors. The xylose-fermenting yeasts are able to grow on media containing
      erythromycin (1 g/L) or diuron (50 mg/L), whereas the Saccharomyces species are
      inhibited by these mitochondrial inhibitors.

PMID- 1393836
TI  - Capsules of Escherichia coli, expression and biological significance.
AB  - Escherichia coli may cause intestinal or extraintestinal infections. Generally,
      extraintestinal E. coli are encapsulated. The capsules are important virulence
      determinants, which enable the pathogenic bacteria to evade or counteract the
      unspecific host defense during the early (preimmune) phase of infection. They
      interfere with the action of complement and phagocytes. This effect is generally
      transient and overcome by capsule-specific antibodies in the immune phase of the
      host defense. In some cases, capsules are not or only poorly immunogenic, as a
      result of structural relationship or identity with host material. Strains with
      such capsules (e.g., K1 or K5) are very virulent. Bacterial capsules consist of
      acidic polysaccharides, which are made up from oligosaccharide repeating units.
      The capsules of E. coli are divided into two groups, which differ in chemistry,
      biochemistry, and genetic organization. All capsular polysaccharides are
      chromosomally determined: those of group I close to his and those of group II
      close to serA. The biosynthesis and surface expression have been extensively
      studied with representatives of group II capsular polysaccharides. It could be
      shown that their biosynthesis is directed from a gene block that determines the
      synthesis of the polysaccharide, its translocation across the cytoplasmic
      membrane, as well as its surface expression in a coordinate process. The chemical
      nature of group II capsular polysaccharides, as well as the mechanism(s) of their
      biosynthesis and expression, is presented.

PMID- 1393837
TI  - Mechanism and regulation of synthesis of aerobactin in Escherichia coli K12
      (pColV-K30).
AB  - The aerobactin operon of the virulence plasmid pColV-K30 of Escherichia coli K12
      consists of four genes for biosynthesis and one for transport of the siderophore.
      Regulation by iron occurs at the transcriptional level and is mediated by a
      ferrous iron binding protein designated Fur (ferric uptake regulation). The
      metallated Fur repressor binds at a palindromic dyad, the "iron box" operator,
      situated in the vicinity of the RNA polymerase attachment site of the promoter.
      Evidence suggests that the ferrous iron enters the C-terminal domain of Fur to
      cause a conformational change in the N-terminal part of the protein. This results
      in greatly enhanced affinity of the repressor for the operator.

PMID- 1393838
TI  - Escherichia coli cytotoxins and enterotoxins.
AB  - Vero cell cytotoxins and cytotonic enterotoxins produced by E. coli are toxic
      proteins, which have been implicated in a number of specific diseases in humans
      and animals. Nomenclature for these toxins is complicated by the existence of
      different names for the same toxin. The Vero cell cytotoxins are called
      verotoxins because they are lethal for Vero cells in culture; they are also known
      as Shiga-like toxins (SLTs) because they are clearly related to Shiga toxin in
      structure, amino acid sequence, mechanism of action, and biological activity.
      SLTs belong to two classes. SLT-I is identical with Shiga toxin and is in a class
      by itself (class I). The other SLTs are closely related to each other and form a
      second class (class II). Class II SLTs include SLT-II, SLT-IIv, SLT-IIvha, SLT
      IIvhb, and SLT-IIva. All SLTs that have been investigated are A-B subunit protein
      toxins, whose A subunits possess N-glycosidase activity against 28S rRNA and
      cause inhibition of protein synthesis in eukaryotic cells. These toxins are
      enterotoxic as well as cytotoxic. SLTs produced in the intestine are absorbed
      into the blood stream and affect vascular endothelial cells in target organs.
      They may also have a direct toxic effect on enterocytes. Diseases in which E.
      coli SLTs have been implicated include diarrhea, hemorrhagic colitis, and
      hemolytic uremic syndrome in humans and edema disease in pigs. Variation in
      receptor specificities among SLTs may be the reason for different disease
      syndromes in different host species. The E. coli enterotoxins belong to three
      distinct classes: heat-labile enterotoxin (LT), heat-stable enterotoxin type I or
      type a (STI, STa), and heat-stable enterotoxin type II or type b (STII, STb).
      There is clear evidence that these cytotonic enterotoxins play an essential role
      in diarrheal disease. LT is an A-B subunit protein toxin, closely related to
      cholera toxin. Following binding of LT to receptors in enterocytes the A subunit
      is internalized. The enzymatically active A subunit transfers ADP-ribose from NAD
      to a GTP-dependent adenylate cyclase regulatory protein, thereby elevating
      intracellular levels of adenylate cyclase. The increased levels of cyclic AMP
      cause stimulation of A kinase and lead to hypersecretion of electrolytes and
      fluid. STI is a small peptide of 18 or 19 amino acids. It binds to receptors in
      enterocytes and stimulates particulate guanyl cyclase. Elevated intracellular
      cyclic GMP stimulates G kinase, resulting in increased Cl- secretion and impaired
      absorption of Na+Cl-. STII is a peptide toxin whose mechanism of action is
      unknown.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1393839
TI  - Virulence determinants of Escherichia coli: present knowledge and questions.
AB  - This paper describes the present state of research on the pathogenicity of
      Escherichia coli and points out the gaps in knowledge that should be filled in
      the future. First, the great versatility of E. coli in producing disease is
      noted, as well as the invaluable contributions that studies of it have made to
      the development of general knowledge on bacterial pathogenicity. Then, the
      biological requirements for pathogenicity: infection of mucous surfaces;
      penetration of those surfaces; multiplication in vivo; interference with host
      defence mechanisms; and damage to the host, are taken in turn, and an enquiry is
      made on how far studies have progressed toward identifying their molecular
      determinants and relating structure to biological action. Only for mucous surface
      adhesins and protein toxins are studies at the structure-function level. Some
      progress has been made on interference with host defence, but little is known
      about competition with commensals on mucous surfaces, invasion into the tissues,
      and growth in vivo.

PMID- 1393840
TI  - Magnetic resonance imaging and 31P magnetic resonance spectroscopy study of the
      effect of temperature on ischemic brain injury.
AB  - Transient forebrain ischemia was induced in rats whose brain temperature was 31,
      33, 35, 38, or 40 degrees C. The development of regional injury was followed
      using magnetic resonance (MR) imaging, with the ultimate extent of neuronal
      injury quantified histopathologically. Animals in the hypothermic groups showed
      minimal changes in MR images over 4 days; normothermic animals showed intensity
      enhancement attributed to progressive edema developing in the striatum and,
      later, in the hippocampus. Ischemia at 40 degrees C resulted in widespread edema
      formation by 1 day post-ischemia; animals in this group did not survive beyond 30
      hours. Histopathological analysis at 4 days (1 day for the hyperthermic group)
      post-ischemia showed that neuronal damage in the normothermic group was confined
      to the hippocampus and striatum. Minimal damage was found in the hypothermic
      groups; damage in the hyperthermic group was severe throughout the forebrain.
      There were no differences in the pre-ischemia 31P MR spectra for the different
      groups. During ischemia, the increase in intensity of the Pi peak and the fall in
      tissue pH increased with temperature in the order hypothermic less than
      normothermic less than hyperthermic group of animals. Post-ischemia energy
      recovery was similar in all groups, while pH recovered more rapidly in
      hypothermic animals.

PMID- 1393841
TI  - Malondialdehyde, glutathione peroxidase, and superoxide dismutase in
      cerebrospinal fluid during cerebral vasospasm in monkeys.
AB  - Cerebral vasospasm may result from lipid peroxidation induced by oxyhemoglobin in
      the subarachnoid space after subarachnoid hemorrhage. To test this theory,
      vasospasm was induced in monkeys by intrathecal injections of oxyhemoglobin or
      supernatant fluid from autologous blood incubated in vitro. Concentration of
      malondialdehyde (MDA), a product of lipid peroxidation, was elevated in
      cerebrospinal fluid (CSF) in association with vasospasm caused by oxyhemoglobin
      and supernatant fluid. Intrathecal injections of methemoglobin or bilirubin did
      not cause vasospasm or increased CSF MDA. Activity of glutathione peroxidase in
      CSF increased significantly after injection of oxyhemoglobin and methemoglobin.
      There were no significant changes in CSF superoxide dismutase activity although
      there was a trend towards higher activities in animals treated with
      oxyhemoglobin, methemoglobin, bilirubin, and supernatant fluid. These results
      show oxyhemoglobin-induced vasospasm is associated with MDA and lipid
      peroxidation in the subarachnoid space. Furthermore, detection of peroxidation
      products after injection of oxyhemoglobin in the absence of erythrocyte membranes
      indicates that oxyhemoglobin may directly damage cerebral arteries and brain by
      inducing lipid peroxidation in these structures. Depletion of free-radical
      scavenging enzymes in CSF did not seem necessary for development of vasospasm. In
      fact, there was a tendency for vasospasm to elevate enzyme activities, as if
      production of scavengers was induced by excess free radicals in the subarachnoid
      space.

PMID- 1393842
TI  - A Canadian population survey on the clinical, epidemiologic and societal impact
      of migraine and tension-type headache.
AB  - Trained telephone interviewers contacted 1,573 adults across Canada about the
      nature and frequency of headaches suffered by them or by others in their
      households. Using a table of pain symptoms and other characteristics abstracted
      from the International Headache Society (IHS) classification, the headaches were
      assigned to migraine headache, tension-type headache or other diagnostic groups.
      Of the households sampled, 59% had at least one headache sufferer in residence.
      The proportion of headache sufferers with migraine was 14%; with tension-type,
      36%; and with both, 14%. Migraine headache caused more disability than tension
      type headache, with nearly 20% of migraine sufferers taking time off work and
      disability lasting for a mean of 1 day. It is concluded that the current
      prevalences of migraine and tension-type headache in Canada fall around the mean
      of previous studies, that the IHS criteria can form a basis for diagnostic
      classification and that the functional impact of migraine has been seriously
      underestimated in the past.

PMID- 1393843
TI  - Comparison of the efficacy and safety of flunarizine to propranolol in the
      prophylaxis of migraine.
AB  - This study was designed to compare flunarizine, a cerebro-specific calcium
      channel antagonist, and propranolol in the prophylaxis of migraine with or
      without aura. Following a 1 month single-blind placebo baseline period, 94
      patients were equitably randomised under double-blind conditions to take
      flunarizine 10 mg daily or propranolol 80 mg twice daily for 4 months. Both
      treatments led to a significant reduction in the frequency of migraines and use
      of rescue analgesics with a significantly greater decrease in number of attacks
      for flunarizine after 1 and 4 months. Neither treatment affected the severity nor
      duration of migraines. Overall, 67% of flunarizine patients and 51% of
      propranolol patients responded positively. Propranolol significantly reduced
      blood pressure and heart rate; flunarizine had no effect on cardiovascular
      function. Weight gain was noted with both treatments. Flunarizine is at least as
      effective as propranolol in the prophylactic treatment of migraine and may have a
      better safety profile.

PMID- 1393844
TI  - The distinctive clinical features of paraneoplastic sensory neuronopathy.
AB  - A 15-year experience with paraneoplastic sensory neuronopathy at the Mayo Clinic
      is reviewed. Of 26 patients with paraneoplastic sensory neuropathy, 19 had small
      cell lung cancer, 4 had breast cancer, and 3 had other neoplasms. There was a
      striking predominance of females (20:6). Neuropathic symptoms (pain, paresthesia,
      sensory loss) were asymmetric at onset, with a predilection for the upper limbs;
      in three patients, symptoms were confined to the arms. Electrophysiologic testing
      revealed absent sensory responses and normal or minimally altered motor
      responses. Slightly more than half the patients had associated autonomic,
      cerebellar, or cerebral abnormalities. In some patients, treatment of the
      neoplasm seemed to halt progression of the neuronopathy, but none had neurologic
      improvement and most continued to worsen, even when the oncologic response was
      good. Distinguishing between paraneoplastic and nonparaneoplastic sensory
      neuronopathies can be difficult, but prominent neuropathic pain, neurologic
      dysfunction involving more than the peripheral sensory system, or an increased
      cerebrospinal fluid protein value should prompt a careful search for a cancer.

PMID- 1393845
TI  - Ventricular size, cognitive function and depression in patients with multiple
      sclerosis.
AB  - The purpose of this study was to explore further the hypothesis that changes in
      cognitive function may occur in the mild stages of multiple sclerosis (MS) by
      determining whether ventricular enlargement was related to cognitive function.
      Ten measures of ventricular size were made in a sample of 123 MS patients with
      mild disability and 60 well-matched healthy controls. In addition, sixteen tests
      of cognitive function and the Beck Depression Inventory were administered. For
      the MS group, there were significant correlations between the ventricular
      measures and cognitive performance but not for the normal controls. Scores on the
      Beck Depression Inventory were not correlated with either cognitive performance
      or ventricular enlargement. These findings suggest that for the MS group
      cognitive impairment was related to the disease process but not to the level of
      depression.

PMID- 1393846
TI  - Amyotrophic lateral sclerosis: interleukin-6 levels in cerebrospinal fluid.
AB  - Recent observations indicate that antibodies to gangliosides are found in many
      patients with amyotrophic lateral sclerosis (ALS). If antigen-antibody complexes
      occur in ALS, elevations of cytokine levels might be expected, among them the
      cytokine interleukin-6 (IL-6). IL-6 is secreted by activated monocytes and other
      cell types and is an important mediator of the inflammatory response. We have
      measured cerebrospinal fluid (CSF) IL-6 levels in patients with ALS and compared
      them with those in psychiatric and neurodegenerative disorders not believed to be
      due to immune disorders of the central nervous system. We found no significant
      differences in CSF IL-6 levels between these groups.

PMID- 1393848
TI  - MRI diagnosis of brainstem cavernous angiomas presenting as tumours.
AB  - We report experience with 11 patients misdiagnosed for years, on the basis of
      computed tomography (CT) and angiography, as harbouring brainstem tumours in whom
      magnetic resonance imaging (MRI) demonstrated cavernous angiomas. Seven had
      undergone external irradiation, 2 had a ventriculo-peritoneal shunt, 2 developed
      aseptic femur necrosis following corticosteroid treatment, 1 had undergone a
      biopsy with a pathological diagnosis of glioma. CT had depicted ill-defined,
      hyperdense, faintly enhancing lesions. Angiography was normal, or showed an
      avascular mass or subtle venous pooling. MRI delineated discrete lesions, typical
      of cavernous angiomas, with a mixed hyperintense, reticulated, central core
      surrounded by a hypointense rim. Six patients subsequently underwent stereotactic
      radiosurgery without changes in clinical status or lesion. Although hemorrhagic
      neoplasms may mimic the clinical course and MRI appearance of cavernous angiomas,
      MRI is useful in the diagnosis of brainstem cavernous angiomas and should be
      performed in patients with suspected brainstem tumours.

PMID- 1393847
TI  - Treatment of acquired autoimmune myasthenia gravis: a topic review.
AB  - We propose a new approach to staging the disease based on clinical and
      immunological response to treatment. We oppose clinical remission to
      immunological remission and define total clinical remission as the goal of
      therapy. We describe the use, side effects and indications of established
      therapies. Acetylcholine esterase inhibitors are only a symptomatic treatment as
      is plasma exchange. Usefulness and limits of thymectomy, corticosteroids and
      immunosuppressants are described here. Their goal is to reduce the auto-immune
      process. Long-term hazards from these medications are described and methods to
      reduce their potential risks are suggested. We suggest the number of patients
      having life threatening complications while undergoing aggressive
      immunosuppression can be reduced by a systematic approach to follow-up. In the
      second part of this review article, adapting management to specific situations is
      emphasized in refractory disease, respiratory failure, neonatal and juvenile
      forms of the disease. The special situation of seronegative myasthenia is
      discussed.

PMID- 1393849
TI  - Stiff-person syndrome.
AB  - The stiff-person syndrome is a disorder of persistent, painful muscle
      contractions predominately affecting the axial musculature. We describe a patient
      with this disorder and review its pathophysiology. Molecular biologic and
      immunologic techniques have recently added to the understanding of the mechanism
      of this disorder. Association with diseases such as diabetes, vitiligo and
      hypothyroidism have strengthened the auto-immune nature of this syndrome. Auto
      antibodies against glutamic acid decarboxylase (GAD), an intraneuronal enzyme,
      have been implicated in the etiology of this unique disease. Therapeutic
      intervention with agents such as benzodiazepines that modify central GABAergic
      activity have demonstrated significant benefit in patients with stiff-person
      syndrome.

PMID- 1393850
TI  - Spontaneous disappearance of an intracranial aneurysm after subarachnoid
      hemorrhage.
AB  - Spontaneous disappearance of an intracranial aneurysm after subarachnoid
      hemorrhage is an uncommon event and usually associated with severe cerebral
      vasospasm, giant aneurysms or the use of antifibrinolytics. We present a young
      woman who suffered a grade 5 subarachnoid hemorrhage with severe vasospasm caused
      by a small anterior communicating artery aneurysm. The patient underwent a slow
      recovery and two years later requested surgery. Angiography demonstrated complete
      disappearance of the aneurysm. The neurosurgeon should be aware that spontaneous
      thrombosis of cerebral aneurysms can occur and ensure that angiography is
      repeated when surgery is significantly delayed.

PMID- 1393852
TI  - Neurocritical care. Highlights from two Austrian meetings. December, 1991.

PMID- 1393851
TI  - Intraventricular central neurocytoma.
AB  - A case of central neurocytoma treated surgically is described. The authors review
      the literature. Emphasis is placed on radiological and pathological features not
      previously described. In particular, the intra-operative ultrasound appearance is
      described. The role of adjunctive radiotherapy is also discussed.

PMID- 1393853
TI  - Surgical training in Canada.

PMID- 1393854
TI  - General surgery training in Canada: are we in trouble?

PMID- 1393855
TI  - Nontertiary surgery in Manitoba.

PMID- 1393856
TI  - Diagnosis and management of thoracic neurogenic tumours.

PMID- 1393857
TI  - Surgical treatment of well-differentiated thyroid cancer.

PMID- 1393858
TI  - Structured abstracts for clinical research manuscripts and reviews.

PMID- 1393859
TI  - Survival of breast-cancer patients with previous or subsequent neoplasms.

PMID- 1393860
TI  - Survival of breast-cancer patients with previous or subsequent neoplasms.
AB  - The authors reviewed retrospectively 1510 patients with breast cancer operated on
      between 1960 and 1980. They compared 1353 patients who had an isolated breast
      cancer (group 1) with 157 patients who also had breast cancer but had other
      cancers either previously or subsequently (group 2). The mean age of patients in
      group 2 was 2 years more than that of patients in group 1. Group 2 patients had
      fewer T3 tumours, more T1 tumours (TNM classification), a lower incidence of
      lymph-node involvement and clinically less advanced tumours than group 1
      patients. Hormonal status, histologic type of tumour and surgical and adjuvant
      treatment were identical in both groups. The 10-year survival rate (considering
      death from breast cancer) was 54.6% in group 1 versus 78.1% in group 2. The
      overall survival rate (considering death from breast cancer or from the other
      cancer) was 54.1% in group 1 versus 64.5% in group 2. Survival was also better in
      group 2 for each clinical stage. The authors conclude that patients who have
      another cancer before or after the development of their breast cancer have a
      better survival rate than those who have isolated breast cancer with no previous
      or subsequent neoplasms.

PMID- 1393861
TI  - Total mastectomy is not always mandatory for the treatment of recurrent breast
      cancer after lumpectomy alone.
AB  - To determine the treatment that offered the best local control for isolated local
      recurrences of breast cancer after lumpectomy without radiotherapy, the authors
      reviewed 355 patients initially treated by lumpectomy (with or without axillary
      dissection) without radiotherapy. Local breast cancer recurred in 79 patients.
      They underwent either repeat partial mastectomy (PM) or completion total
      mastectomy (TM). Twenty-four patients (5 TM, 19 PM) received radiotherapy. Local
      control was defined as the absence of further recurrence of breast or chest-wall
      cancer. The 19 patients treated with repeat PM and radiotherapy had an actuarial
      local control rate of 82% at 5 years. Those treated with TM (28 patients)
      [corrected] or TM plus radiation (5 patients) had rates of local control of 60%
      and 52% respectively. Although there were no significant differences between the
      TM and PM plus radiotherapy groups, the 27 patients who had a repeat PM without
      radiotherapy had a significantly lower rate of local control (32%, p < 0.005).
      Treatment of recurrent breast cancer with PM and radiotherapy is a viable
      alternative to TM for enhancing local control. Repeat PM alone gave much poorer
      results. The authors conclude that local cancer recurrences after lumpectomy
      alone do not necessarily require TM and can often be treated with repeat excision
      and radiotherapy.

PMID- 1393862
TI  - Surgery for critical aortic stenosis in newborns is still good therapy after 25
      years.
AB  - Because of the high operative mortality in newborn infants with critical aortic
      stenosis, new therapeutic modalities have emerged. The authors reviewed their
      results of surgery for this condition in newborn infants between January 1964 and
      December 1990. Thirty-seven infants were operated on for critical aortic
      stenosis, which was diagnosed at a mean patient age of 14.5 days. The surgical
      procedure was done at a mean patient age of 37 days. Five infants died
      intraoperatively of ventricular fibrillation at the time of incision.
      Transventricular valvotomy was attempted in 4 infants, and the remaining 28
      infants underwent transaortic valvuloplasty. Overall survival improved markedly
      in the last 5 years of the study, from 31% to 75%. All patients who had
      transventricular valvotomy died, as did the only infant with previous
      percutaneous aortic valvuloplasty. Of the infants who died, 38% weighed less than
      3000 g at the time of operation compared with 13% of the survivors (p < 0.05).
      The duration of cardiopulmonary bypass was also identified as a risk factor (p =
      0.001). Of the surviving infants, 93% were followed up at a mean of 66 months.
      All but one were in New York Heart functional class I or II. The following risk
      factors were identified for operative mortality: year of surgery, preoperative
      hemodynamic condition, associated anomalies of the left ventricle, surgical
      weight less than 3000 g, transventricular valvotomy, year of surgery and
      prolonged cardiopulmonary bypass. Because of the much improved survival recently,
      surgery remains a good therapeutic choice for critical aortic stenosis in the
      newborn infant.

PMID- 1393863
TI  - Descending thoracic aortic aneurysms: surgical treatment with the Gott shunt.
AB  - Over the past 16 years, 267 consecutive patients underwent surgery for a
      descending thoracic aortic aneurysm. To provide optimal protection of surrounding
      organs during aortic occlusion, a 9-mm Gott shunt was used for distal perfusion
      in all cases. The shunt was placed preferentially between the ascending aorta and
      the descending aorta; however, alternative sites of proximal and distal
      cannulation were chosen according to the location and the extent of the
      aneurysmal disease and the presence of a concomitant aneurysm along the aortic
      conduit. In one-third of the patients, a flowmeter on the shunt recorded shunt
      flows, which varied from 1100 mL/min to 4900 mL/min (mean 2526 mL/min). Because
      the highest shunt flows were obtained with proximal systolic pressures lower than
      140 mm Hg, nitroglycerin and nitroprussate were used routinely to improve distal
      perfusion by arterial vasodilation and release of proximal organs from a
      circulatory overload. The mean aortic cross-clamp time was 33 minutes for the
      entire series but was reduced to 25 minutes for the last 140 patients. The
      hospital death rate was 14.6% overall (12.2% if ruptured aneurysms were
      excluded). Of the 267 patients, 260 survived the operation and underwent clinical
      neurologic assessment. No paraplegia or other spinal-cord ischemic deficit
      occurred.

PMID- 1393864
TI  - Central neurogenic tumours of the thoracic region.
AB  - Of special concern in the management of neurogenic tumours arising in the thorax
      is spinal-cord compression resulting from either intraspinal lesions or vertebral
      body destruction and collapse. A review of 16 cases disclosed three dumbbell
      tumours, six intrathoracic tumours, one case of neurofibromatosis with multiple
      intraspinal neurogenic tumours, two malignant neurogenic tumours with vertebral
      body destruction causing spinal-cord compression and four foraminal lesions with
      central intraspinal (extradural) extension. There were 3 men and 13 women,
      ranging in age at the time of operation from 37 to 79 years. Three patients, of
      the six with intrathoracic tumours, were asymptomatic; the remaining 13 had
      preoperative symptoms ranging in duration from 3 weeks to 12 months (average, 9
      months). Back pain with intercostal neuralgia was present in eight patients and
      neurologic signs were present in six patients. A routine chest radiograph was
      abnormal in 10 patients, and x-rays of the thoracic spine were abnormal in 4 of
      the other 6 patients. The tumour was excised surgically in all patients.
      Complications developed postoperatively in two patients: one had Horner's
      syndrome, transient paraparesis and bleeding; the other had a small subarachnoid
      cutaneous fistula. The authors conclude that dumbbell neurogenic tumours and
      those causing vertebral-body destruction and collapse demand a multidisciplinary
      one-stage surgical approach. If the lesion is malignant and resection is not
      complete, radiotherapy or chemotherapy is necessary.

PMID- 1393865
TI  - Colorectal leiomyosarcomas: a pathobiologic study with long-term follow-up.
AB  - Colorectal leiomyosarcoma (CLM) is an uncommon tumour. Reports of its occurrence
      have been published mostly as single cases or small series. This study documents
      12 cases of CLM that were seen over a 28-year period in Saskatchewan. The annual
      incidence of CLM was 0.45 per million people and constituted 0.12% of all
      colorectal malignant tumours seen during the study period. CLMs had a
      predilection for the rectum and sigmoid and commonly were associated with rectal
      bleeding or abdominal pain. More than half the tumours were detected by
      sigmoidoscopy. A correct preoperative or intraoperative histologic diagnosis of
      leiomyosarcoma was made in only two out of six cases. A potentially curative
      surgical procedure was done in 10 of the 12 patients. The mean follow-up was 6.9
      years. Eight patients had tumour recurrence or metastasis, or both. From the
      findings of this study the authors recommend wide excision of colorectal smooth
      muscle tumours whenever there is a suggestion of malignancy.

PMID- 1393866
TI  - Thoracoscopic transthoracic dorsal sympathectomy.
AB  - The authors report on the three patients who underwent thoracoscopic
      transthoracic dorsal sympathectomies by the techniques of minimal-access surgery
      learned from laparoscopic cholecystectomy. All three had histologic confirmation
      of removal of the sympathetic chain and have had an encouraging early
      postoperative result. The authors believe that thoracoscopic transthoracic dorsal
      sympathectomy can be accurately and safely performed and will become the method
      of choice for dorsal sympathectomy.

PMID- 1393867
TI  - Prevention of herpes simplex virus infection by oral acyclovir after cardiac
      transplantation.
AB  - Infection with herpes simplex virus is common among immunosuppressed patients. In
      an attempt to prevent such infection, 58 patients (group 1) who underwent cardiac
      transplantation between 1987 and 1990 were given acyclovir (200 mg orally three
      times a day) prophylactically throughout their postoperative hospital stay (mean
      22 days +/- 1 day). The patients' immunosuppressive protocol included
      cyclosporine, azathioprine and prednisone. The course of these patients was
      compared to that of 24 patients (group 2) who underwent cardiac transplantation
      between 1983 and 1986 but were not given prophylactic antiviral treatment
      postoperatively. The immunosuppressive protocol in these patients consisted of
      cyclosporine and prednisone. Herpes infection developed during the 1st year in 5
      patients (9%) in group 1 and in 11 patients (46%) in group 2 (p < 0.05). The
      actuarial rates of freedom from herpes infection at 1, 6 and 12 months after
      transplantation were 100%, 98% +/- 2% and 95% +/- 3%, respectively, in group 1
      and 82% +/- 7%, 58% +/- 11%, 53% +/- 11% in group 2. All viral infections were
      cutaneous or mucosal, except for one, which developed in a patient with
      pneumonia. All infections responded well to treatment, although one patient with
      an infected cornea was left with a permanent visual deficit. The authors conclude
      that prophylaxis of herpes simplex virus infection with acyclovir administered
      orally in the early postoperative period is effective in preventing viral
      infections during the 1st year after cardiac transplantation.

PMID- 1393868
TI  - Unilateral versus bilateral thyroid resection in differentiated thyroid
      carcinoma.
AB  - Risk-group definitions have been developed recently in an attempt to clarify
      which operation to do for whom in differentiated thyroid carcinoma. The authors
      attempted to confirm the validity of an age-based risk-group definition for
      identifying patients at high risk of death from thyroid carcinoma and to test
      whether the degree of surgical resection in either high- or low-risk groups
      affected patient survival. An age-based risk-group definition was used in the
      retrospective analysis of 161 patients with differentiated thyroid carcinoma seen
      at the Saskatoon Cancer Centre, University of Saskatchewan, between 1933 and
      1964. A significant difference was found in the death rate between low- and high
      risk groups (4.3% versus 47% respectively). This confirms the validity of such an
      age-based risk-group definition. Although a long-term survival benefit was
      suggested with the use of bilateral thyroid resection in high-risk patients, the
      difference was not significant. In low-risk patients, there was no difference in
      the survival rate between patients who underwent unilateral or bilateral thyroid
      resection, followed up for as long as 55 years.

PMID- 1393869
TI  - Management of papillary carcinoma arising in thyroglossal-duct anlage.
AB  - Cysts of the thyroglossal duct are common congenital abnormalities. They present
      as asymptomatic midline cervical swellings. The risk of malignant change is low;
      only 103 cases have been reported in the world literature, 85% of which were
      papillary adenocarcinomas. The appropriate treatment for this condition remains
      controversial. The authors describe three patients who had papillary carcinoma
      contained within a thyroglossal-duct rest. All were treated by cyst resection and
      thyroid suppression, but without thyroidectomy and radioactive thyroid ablation.
      Postoperatively, all patients remained disease free, with no recurrence at follow
      up ranging from 10 to 29 years. Isolated papillary carcinomas arising from
      primitive thyroid remnants, associated with a palpably normal thyroid gland at
      surgery and a negative thyroid scan, can be treated adequately by excising the
      thyroglossal mass.

PMID- 1393870
TI  - Nontertiary surgery in Manitoba: comparison of provincial and teaching-hospital
      data.
AB  - Do the teaching hospitals in Manitoba provide a suitable spectrum and sufficient
      numbers of operations to prepare surgeons for practice in Manitoban communities?
      To answer these questions, the author reviewed the types and frequencies of all
      operations performed in Manitoba during 1985 and 1986 and compared them with all
      operations performed in the two Manitoba teaching hospitals for the same years.
      The 189,380 operations studied were categorized according to the surgical
      specialist who usually performed each operation in the teaching hospitals. For
      some procedures commonly performed in the province as a whole, there were too few
      operations performed in the teaching hospitals to provide sufficient experience
      for the trainees. A breakdown of nontertiary operations performed in Manitoba
      revealed that 39% were in the category of general surgery, 29% were in gynecology
      and operative obstetrics, 17% were in orthopedics, 10% were in urology and 4%
      were in plastic surgery. The author concludes that a surgeon going to a smaller
      community as the only surgical specialist requires training of a broader scope
      than is provided currently in the standard general-surgery training programs in
      Manitoba.

PMID- 1393872
TI  - The Advanced Trauma Life Support course for senior medical students.
AB  - The authors conducted the Advanced Trauma Life Support (ATLS) Course for 90
      students who were in their 4th year of medicine at the University of Manitoba.
      The impact of the course was evaluated through questionnaires completed by
      students, instructors and emergency-room physicians. The students' performances
      were also compared with those of 96 practising physicians who took the ATLS
      course in Manitoba. The failure rate for students (3.3%) was not statistically
      different from that for practising physicians (4.2%). Overall, the students'
      performances in the written test were better (55% of students scored over 90% on
      the test compared with 15% of practising physicians). The student-to-faculty
      ratio was 1.5:1 and included 21 physician-instructors. Ninety-five percent of the
      faculty and students suggested that this course should be mandatory in the 4th
      year curriculum of medicine and that the course improves trauma care provided by
      the students and interns by increasing their confidence and improving
      communication with specialist surgeons. However, 10% of the faculty suggested
      that more time should be allocated to the surgical-skills practicum. The authors'
      experience with this program suggests that the ATLS course should be uniformly
      incorporated in the Canadian undergraduate 4th year medical curriculum and that
      techniques used in this course should be considered in other areas of the
      undergraduate medical curriculum.

PMID- 1393871
TI  - A technical-skills course for 1st-year residents in general surgery: a
      descriptive study.
AB  - The proper teaching of operative skills to surgical residents is increasingly
      constrained by operative time, complex procedures and medicolegal concerns. A
      technical-skills program was developed and introduced over a 3-year period to 28
      1st-year residents in general surgery. To introduce the residents to the
      principles of surgical techniques in a simulated environment outside the
      operating room, the program consisted of a combination of two didactic sessions
      and six "wet labs" taking 3 to 4 hours per week for 8 weeks between January and
      March each year. The didactic sessions included instruction on suture material
      and the use of stapling devices; the "wet lab" used a "hands-on" approach.
      Educational objectives in the "wet lab" included instruction on preparation of
      the patient and draping, aseptic technique, principles of bowel anastomosis,
      incisions, instrument use and handling, principles of hemostasis, intraoperative
      surgical emergencies, surgical assisting and overall conduct in the operating
      room. The residents' surgical technique and skills improved over the course
      period. The overall value, teaching and understanding of surgical principles were
      rated highly. Problems cited during resident feedback were the use of live
      animals and insufficient time to practise. The efficacy of a surgical-skills
      program has been demonstrated, but its effectiveness requires further evaluation.

PMID- 1393873
TI  - A family exhibiting carotid body tumours.
AB  - The authors describe the surgery carried out for 11 carotid body tumours (CBTs)
      that were found in three generations of a Greek family. Eight patients with CBTs
      were operated upon at St. Joseph's Health Centre, Toronto, within 1 year. Three
      patients had bilateral CBTs, which were removed in two stages. Only one of the
      CBTs occurred in a female. Seven CBTs were excised by meticulous subadventitial
      dissection. In the eighth, a previous attempt at removal in another hospital had
      proved unsuccessful, and excision of the tumour required ligation of the external
      carotid artery and partial excision of the carotid bulb. The authors conclude
      that most CBTs can be excised directly without ligation, shunts or bypasses. In
      eight operations carried out on five patients, the only complication was a
      transient neuropraxia of the hypoglossal nerve that resolved within 2 weeks.

PMID- 1393874
TI  - Bronchogenic cyst masquerading as a chronic post-traumatic pseudoaneurysm of the
      aortic isthmus.
AB  - The serious nature of false aneurysms that develop in the aortic isthmus after
      blunt chest trauma is well known. The authors describe the case of a 33-year-old
      woman who presented with symptoms of chronic post-traumatic pseudoaneurysm of the
      aorta 3 months after blunt chest trauma. Radiologic investigations could not
      substantiate an aortic disruption. A bronchogenic cyst masquerading as a false
      aneurysm of the aorta was identified at thoracotomy. Bronchogenic cysts are one
      of the most common causes of primary mid-mediastinal masses and should be
      considered as potential causes of mid-mediastinal enlargement. However, this
      consideration should not delay urgent surgery if vascular damage cannot be ruled
      out.

PMID- 1393875
TI  - Surgical management of fulminant pseudomembranous colitis.
AB  - The presentation of pseudomembranous colitis ranges from mild self-limiting
      diarrhea to fulminant colitis with overwhelming sepsis. The management of the
      severe forms of this disease, including the role of surgical intervention, is
      poorly defined. To evaluate the management and outcome in severe cases, the
      authors reviewed the records of six patients (four women, two men) seen at The
      Toronto Hospital between 1985 and 1989 with pseudomembranous colitis manifesting
      as fulminant colitis. The patients ranged in age from 19 to 69 years (mean 52
      years). All presented with nonbloody diarrhea, had peritoneal signs and were
      severely dehydrated, and all had received antibiotics between 4 days and 6 weeks
      before the onset of symptoms. The mean preoperative leukocyte count was 40.9 x
      10(9)/L. Radiologically, the colon appeared to be dilated in three patients. Two
      patients were operated on immediately. The other four were treated medically, but
      three of them required surgery within 24 hours of presentation. Four (67%) of the
      six patients died. All four had been treated surgically. The mean age of the
      survivors was 28 years compared with 64 years for those who died.
      Pseudomembranous colitis can present as severe acute colitis and can carry a high
      mortality, especially in the aged. Surgical treatment may be required in those
      who fail to respond to medical management or have peritoneal signs.

PMID- 1393876
TI  - Surgical treatment in non-neoplastic parotid disease: indications and results.
AB  - Non-neoplastic disease of the parotid gland is an important entity, requiring
      differential diagnosis and management. The incidence of non-neoplastic parotid
      disease (NNPD) is increasing and makes up about 25% of cases for which
      parotidectomy is indicated. NNPD can be categorized as type I (asymptomatic soft
      diffuse enlargement or circumscribed firm nodular enlargement) or type II
      (inflammatory lesions with recurrent pain and swelling, obstructive or
      nonobstructive). Concern over possible malignancy is highest in type I nodular
      lesions and least in type II lesions. Operative treatment may be indicated for
      exclusion of tumour, relief of recurrent pain and swelling and patient anxiety.
      In 62 patients with NNPD who were operated on, the relevant clinical factors
      included radiation, diabetes, tuberculosis, Sjogren's syndrome and pulmonary
      sarcoidosis. Superficial parotidectomy was effective, being associated with low
      morbidity, and can be recommended as acceptable treatment, providing there is a
      complete patient history and operation is carried out by a surgeon experienced in
      parotid surgery.

PMID- 1393878
TI  - Preventing hepatitis B.

PMID- 1393877
TI  - Psychology and women subject of Toronto conference.

PMID- 1393879
TI  - Preventing hepatitis B.

PMID- 1393880
TI  - Catch them young.

PMID- 1393881
TI  - Training physicians to be administrators.

PMID- 1393883
TI  - Maintenance of competence.

PMID- 1393882
TI  - Ontario's proposed consent laws: 2. Advocacy.

PMID- 1393884
TI  - HIV-seropositive surgeons: informed consent and public health policy.

PMID- 1393885
TI  - Toward integrated medical resource policies for Canada: 6. Remuneration of
      physicians and global expenditure policy.

PMID- 1393886
TI  - "Brittled" bones of early Brits.

PMID- 1393887
TI  - Risk of breast cancer in women with breast cysts.
AB  - OBJECTIVE: To study the occurrence of breast cancer in women with breast cysts.
      DESIGN: Prospective follow-up study. SETTING: Office surgical practice. PATIENTS:
      All 742 women referred to the practice with breast cysts diagnosed by means of
      aspiration or, occasionally, biopsy between 1969 and 1985. MAIN OUTCOME MEASURES:
      The incidence of breast cancer and the number of years between diagnosis of
      breast cyst and diagnosis of cancer. The observed number of cases of breast
      cancer was compared with the expected number, calculated from Ontario rates of
      breast cancer. RESULTS: Fifteen of the women died but did not have breast cancer.
      No follow-up information was available for five women. Another 38 were lost to
      follow-up; they did not have breast cancer at the last contact, after 2 to 17
      years of follow-up. These patients were withdrawn from the study in the year in
      which they died or were last observed. By 1990, 34 (5%) of the women had breast
      cancer. The overall ratio of observed:expected cases of cancer was 3.04 (95%
      confidence interval 2.09 to 4.28). Breast cancer developed after 7.5 years, but
      the average length of follow-up was only 10.1 years. Only 3.8% of 374 women after
      10 years and 5.4% of 141 women after 15 years had breast cancer. CONCLUSION:
      Women who have a gross breast cyst are at moderately increased risk of breast
      cancer, which usually develops only after many years.

PMID- 1393888
TI  - Non-insulin-dependent diabetes mellitus in Indian children in Manitoba.
AB  - OBJECTIVE: To report on our 7-year experience with non-insulin-dependent diabetes
      mellitus (NIDDM) in native Indian children in Manitoba and to raise the awareness
      of physicians about the difficulties in the classification and management of
      hyperglycemia in Indian children. DESIGN: Case series. PATIENTS: All Indian
      children under 15 years of age referred for evaluation and management of diabetes
      to the diabetes clinic at the Children's Hospital of Winnipeg between 1984 and
      1990 who did not have a history of diabetic ketoacidosis. MAIN RESULTS: Sixteen
      girls and four boys aged 7 to 14 years at the time of diagnosis were identified
      as having NIDDM. All 16 children whose family history could be confirmed had at
      least one parent with NIDDM. Five of the 20 complained of polyuria or nocturia;
      the remainder presented with asymptomatic glycosuria. At the time of diagnosis
      the random serum glucose level varied from 15.0 to 30.8 mmol/L, the fasting serum
      insulin level from 45 to 300 pmol/L and the total glycated hemoglobin level from
      7.1% to 23.3%. Twelve of the children had been followed for at least 4 years. Six
      of the 12 had received insulin therapy at some time, including during pregnancy.
      At the time of writing, none was receiving therapy with insulin or orally given
      hypoglycemic drugs. All were encouraged to follow a weight-reduction diet and
      exercise regimen. During follow-up the mean total glycated hemoglobin level for
      each patient varied from 9.1% to 20.9%; none maintained a glycated hemoglobin
      level in the normal range. CONCLUSIONS: NIDDM occurs in Indian children under 15
      years of age. The clinical features at presentation occasionally mimic those of
      insulin-dependent diabetes. A strong family history of NIDDM and lack of diabetic
      ketoacidosis during follow-up support the diagnosis of NIDDM. Adherence to a diet
      and exercise regimen has been poor. The conventional diabetes education approach
      may not be appropriate for this population.

PMID- 1393889
TI  - A case of bromadiolone (superwarfarin) ingestion.

PMID- 1393891
TI  - Benefits outweigh risks in breast-feeding by HIV-infected mothers in Third World:
      WHO.

PMID- 1393890
TI  - The life of Sir Charles Tupper. 1939.

PMID- 1393892
TI  - Louis Riel and the insanity plea that never came.

PMID- 1393894
TI  - A homeopathic fatality.

PMID- 1393893
TI  - Foreign medical graduates face an uphill struggle for coveted Canadian
      internships.

PMID- 1393895
TI  - Guidelines for laboratory physicians acting as directors of laboratories without
      an on-site pathologist. The Section of Clinical Pathology, Canadian Association
      of Pathologists.

PMID- 1393896
TI  - Risk language preferred by mothers in considering a hypothetical new vaccine for
      their children.
AB  - OBJECTIVES: To determine the type of risk language preferred by mothers
      considering the use of hypothetical new vaccine for their children and to compare
      their choice with what their physicians perceived they would prefer. DESIGN: Mail
      survey. SETTING: Thirteen family practices in southwestern Ontario. PARTICIPANTS:
      Women with at least one child between the ages of 6 months and 5 years and their
      physicians. MAIN OUTCOME MEASURES: Preferred risk language and physicians'
      predictions about patient preference. RESULTS: Of the 226 women sent the
      questionnaire 208 (92%) responded. Of the 192 who indicated their risk language
      preference 118 (61%) chose a numeric statement. Of the 11 physicians who answered
      the question 8 (73%) predicted that their parents would prefer non-numeric
      statements. Although the women in the study were more likely to be married, were
      better educated and had higher family incomes than women of the same age in the
      Ontario population, risk language preference was not found to be related to any
      of those demographic characteristics. CONCLUSION: Physicians must be prepared to
      outline the risks associated with vaccination in both quantitative and
      qualitative terms.

PMID- 1393897
TI  - Burns associated with fondues.
AB  - OBJECTIVE: To describe the causes of burns associated with fondues. DESIGN:
      Descriptive case series. PATIENTS: All 17 patients admitted to a burn centre
      between Apr. 1, 1985, and Mar. 31, 1990, whose burns were associated with fondue.
      Eleven agreed to complete a telephone interview. RESULTS: The age of the 17
      patients varied from 2 to 56 (mean 27) years. Two causes were identified:
      spilling of the contents of the fondue pot and explosion of the fondue fuel when
      added to the burner during a meal. The telephone interview revealed that eight
      people other than the respondents were burned during the same accidents.
      CONCLUSION: Although we identified only badly burned patients the problem may be
      more extensive. The knowledge of specific causes of burns from handling fondue
      equipment indicates that preventive action should be undertaken. More
      epidemiologic information is needed to obtain a precise estimate of the magnitude
      of this public health problem.

PMID- 1393898
TI  - Adverse events after hepatitis B vaccination.

PMID- 1393899
TI  - Revised guidelines for booster vaccination against hepatitis B.

PMID- 1393900
TI  - How it all began. 1967.

PMID- 1393901
TI  - OMA-CMPA confrontation sign of stresses facing organized medicine.

PMID- 1393902
TI  - Canadian cancer reference centre does its work without fanfare.

PMID- 1393904
TI  - Tattooing technique puts finishing touches on plastic surgeon's work.

PMID- 1393903
TI  - South America's cholera pandemic provides lesson in public health, politics.

PMID- 1393905
TI  - Make helmet use mandatory for all bicyclists, CMA recommends.

PMID- 1393906
TI  - Sexual abuse by physicians beginning to emerge as an issue in UK, too.

PMID- 1393907
TI  - Nurse practitioners and family medicine.

PMID- 1393908
TI  - Nurse practitioners and family medicine.

PMID- 1393909
TI  - Getting the facts straight.

PMID- 1393910
TI  - A guide to direct measures of patient satisfaction in clinical practice.

PMID- 1393911
TI  - Niacin versus niacinamide.

PMID- 1393912
TI  - Niacin versus niacinamide.

PMID- 1393913
TI  - Ten years of AIDS.

PMID- 1393914
TI  - Timing of the Medical Council of Canada clinical examination.

PMID- 1393916
TI  - The antismoking lobby: crusaders or zealots?

PMID- 1393915
TI  - Toward integrated medical resource policies for Canada: 9. Postgraduate training
      and specialty certification.

PMID- 1393917
TI  - The antismoking lobby: crusaders or zealots.

PMID- 1393918
TI  - The antismoking lobby: crusaders or zealots.

PMID- 1393919
TI  - The antismoking lobby: crusaders or zealots.

PMID- 1393920
TI  - The application of universal precautions.

PMID- 1393921
TI  - Universal precautions not justified.

PMID- 1393922
TI  - Program evaluation in health care.

PMID- 1393923
TI  - Best wishes from Russia.

PMID- 1393924
TI  - Breast implants: quo vadis?

PMID- 1393925
TI  - Can we afford to screen immigrants for HIV infection?

PMID- 1393926
TI  - Public opinions about health care. Health Services Research Group.

PMID- 1393927
TI  - Summary of the report on silicone-gel-filled breast implants. Independent
      Advisory Committee on Silicone-Gel-filled Breast Implants.

PMID- 1393928
TI  - Consensus statement from the workshop on the teaching and assessment of
      communication skills in Canadian medical schools.

PMID- 1393929
TI  - Dangers of immunosuppressive therapy in hepatitis B virus carriers.
AB  - OBJECTIVE: To identify the risk of hepatic failure in hepatitis B virus (HBV)
      carriers given intermittent immunosuppressive therapy. DATA SOURCES: The key
      words "immunosuppression" and "hepatitis B" were used to search MEDLINE for
      relevant articles in English published from 1970 to 1990; the bibliographies of
      these articles were reviewed for additional publications. Also included were
      articles published in 1991. STUDY SELECTION: Articles were included if they
      documented the use of immunosuppressive drugs to treat chronic hepatitis B or
      another condition in patients at high risk for the HBV carrier state. RESULTS:
      Long-term immunosuppressive therapy has not improved the survival of patients
      with chronic hepatitis B. The withdrawal of such therapy from HBV carriers has
      resulted in a flare-up of potentially fatal hepatitis in 20% to 50%, regardless
      of whether underlying liver disease was present. The presence of replicating
      viral DNA in the serum of HBV carriers may identify those who are at high risk of
      the deleterious effects of immunosuppressive therapy. CONCLUSIONS: Long-term
      immunosuppressive therapy is not advised for liver disease in HBV carriers. For
      other conditions in such people continuous rather than intermittent therapy is
      safer. Patients at high risk for hepatitis B should be screened for this virus
      when immunosuppressive therapy is contemplated.

PMID- 1393931
TI  - Sexual assault tracking study: who gets lost to follow-up?
AB  - OBJECTIVES: To determine whether loss to follow-up can be predicted in patients
      who present to an emergency sexual assault assessment service and to generate
      hypotheses regarding the prediction of loss to follow-up on the basis of patient
      characteristics, assault characteristics and the services provided. DESIGN:
      Prospective, exploratory study. SETTING: Emergency department functioning as a
      regional sexual assault centre in a tertiary care hospital. PATIENTS: All 294
      women over the age of 16 years who presented to the emergency department with a
      complaint of sexual assault and consented to be followed up. INTERVENTIONS:
      Telephone interviews at 24 to 48 hours and 1 month after presentation; face-to
      face interviews after 1 week, 3 months and 6 months. MAIN OUTCOME MEASURES:
      Follow-up status (tracked versus lost to follow-up), State-Trait Anxiety
      Inventory (STAI-Y), Beck Depression Scale (Beck) and Rape Trauma Symptom Rating
      Scale (RTSRS). RESULTS: At 24 to 48 hours 136 (46%) of the patients could not be
      reached. Only 61 (21%) were still tracked at 6 months. Loss to follow-up at 1
      month accurately predicted loss to follow-up at 6 months in 209 (98%) of 214
      patients. For tracked patients the STAI-Y and Beck scores improved over 6 months.
      These scores at 1 week did not predict follow-up status at 6 months, but the
      numbers were small. Subjects with a higher RTSRS score at 24 to 48 hours were
      most likely to remain tracked throughout the 6 months. CONCLUSIONS: Decisions
      regarding how vigorously to track patients with a complaint of sexual assault can
      tentatively be based on the characteristics of the victim and of the assault. We
      hypothesize that the characteristics predicting loss to follow-up include denial
      and avoidance behaviour, lack of a telephone number or forwarding address,
      history of a psychiatric condition, a disability (e.g., deafness),
      characterization as a "street person," a high degree of violence or injury in the
      assault, and threat by the assailant. Although a predictive model requires
      further data, crisis intervention services in an emergency department are
      essential, given the large number of patients lost to follow-up.

PMID- 1393932
TI  - Garage door injuries in children.

PMID- 1393930
TI  - Economic impact of HIV infection and coronary heart disease in immigrants to
      Canada.
AB  - OBJECTIVE: To compare the direct health care costs of illnesses associated with
      the human immunodeficiency virus (HIV) and of coronary heart disease (CHD) in
      immigrants to Canada. DESIGN: Comparative cost analysis. PARTICIPANTS: All people
      who immigrated to Canada in 1988. The numbers with HIV infection and CHD were
      estimated from country-specific HIV seroprevalence data and national CHD
      mortality statistics and data from the Framingham study. Health care costs,
      projected over the 10 years after immigration, were calculated on the basis of
      data from the Hospital Medical Records Institute and provincial fee schedules.
      RESULTS: Of the 161,929 immigrants in 1988, 484 were estimated to be HIV
      positive. The total cost of treatment of HIV-related illnesses from 1989 to 1998
      (discounted at 3%) would be $18.5 million: $17.1 million would be spent on the
      outpatient and inpatient care of the HIV-positive immigrants, $1.0 million on
      care of the subsequently infected sexual partners and $0.4 million on care of the
      HIV-positive children born to seropositive immigrant women. In comparison, CHD
      would develop in 2558 immigrants during the same 10-year period. The total CHD
      costs would be $21.6 million: $8.4 million would be spent on treating myocardial
      infarction, $3.2 million on coronary artery bypass grafting, $1.6 million on
      pacemaker insertion and $8.4 million on treating other CHD events. CONCLUSIONS:
      The economic impact of HIV infection in immigrants to Canada is similar to that
      of CHD. This comparison identifies an important shortcoming in current
      immigration policy: economic considerations can be arbitrarily applied to certain
      diseases, thereby discriminating against specific groups of immigrants.

PMID- 1393934
TI  - The most northerly practice in Canada. 1935.

PMID- 1393933
TI  - Tissue-specific regulation of lipoprotein lipase.

PMID- 1393935
TI  - Providing mental health services in northern Newfoundland, Labrador a unique
      challenge.

PMID- 1393936
TI  - Canadians' obsession with thinness provides full-time work for Alberta
      psychiatrist.

PMID- 1393937
TI  - Wasted resources a major problem for Argentinian health care system.

PMID- 1393938
TI  - Canadian MDs and nonphysicians rate health care system highly, US survey reveals.

PMID- 1393939
TI  - Revised U of T medical curriculum will emphasize student-patient interaction.

PMID- 1393940
TI  - U of T not the only Ontario medical school heavily involved in curriculum
      renewal.

PMID- 1393941
TI  - Growing number of elderly patients will mean more ethical issues for MDs,
      conference told.

PMID- 1393942
TI  - New McGill centre to concentrate on treatment of benign prostatic disease.

PMID- 1393943
TI  - Once upon a midnight dreary: the life and addictions of Edgar Allan Poe.

PMID- 1393944
TI  - Pathogenetic aspects of allergic and irritant contact dermatitis.

PMID- 1393945
TI  - Airborne contact dermatitis.

PMID- 1393946
TI  - Occupational contact dermatitis from exposure to epoxy resins and acrylates.

PMID- 1393947
TI  - Occupational drug dermatitis.

PMID- 1393948
TI  - Occupational contact dermatitis from rubber.

PMID- 1393949
TI  - Occupational contact dermatitis to plants.

PMID- 1393950
TI  - Fiberglass dermatitis.

PMID- 1393951
TI  - Pesticides in occupational contact dermatitis.

PMID- 1393952
TI  - Occupational contact dermatitis from paints.

PMID- 1393953
TI  - Prevention of occupational dermatitis.

PMID- 1393954
TI  - Patch testing and detective work in the workplace.

PMID- 1393955
TI  - AIDS in the workplace.

PMID- 1393956
TI  - Occupational contact urticaria.

PMID- 1393957
TI  - Occupational acne.

PMID- 1393958
TI  - Occupational skin granulomas.

PMID- 1393960
TI  - Occupational dermatitis from physical causes.

PMID- 1393959
TI  - Occupational cutaneous infections.

PMID- 1393961
TI  - Industrial and occupational dermatitis. Outlines for future research.

PMID- 1393962
TI  - Advanced nursing practice: issues and trends.

PMID- 1393963
TI  - Ethical dilemmas in the care of premature infants.
AB  - Advanced technology has improved the survival rate of infants of low birthweight
      and gestational age, but at the cost of long periods of hospitalization and
      unpredictable long-term prognosis. The neonatal clinical nurse specialist (CNS)
      has a responsibility to assist the staff and family in dealing with the ethical
      dilemmas that surround these patients. This article will present a brief history
      of neonatal care and decision making and will address the issues of uncertain
      outcome, treatment judgment standards, withdrawing vs. withholding aggressive
      treatment, and economic impact. The role of the CNS in educating and supporting
      the staff and family to assume a larger part in ethical choices is also
      discussed.

PMID- 1393964
TI  - Collaboration for comprehensive care.

PMID- 1393965
TI  - HIV-infected client care: case management and the HIV team.
AB  - No one discipline can meet the complex needs of the HIV-infected client. Because
      of the diverse nature of disease manifestations, an HIV Team concept is promoted.
      The clinical nurse specialist (CNS) is uniquely prepared to initiate the team and
      support holistic client care through case management. Current HIV statistics with
      implications for the rural community are provided, and reasons for the lack of
      community involvement with HIV care are suggested. The case study illustrates
      complex needs of an HIV-infected woman, as well as issues that evolve during HIV
      infected client care. Interventions that promote care for persons living with HIV
      in addition to support of involved health care workers are addressed. Practical
      suggestions for initiating this process are included.

PMID- 1393966
TI  - Development of a model of transitional care for the HIV-positive child and
      family.
AB  - The provision of high-quality, cost-effective care to Human Immunodeficiency
      Virus (HIV)-infected adults and children is a national priority. During 1991 the
      number of infected children is expected to increase to over 3,000, with at least
      2,000 additional cases manifesting some symptoms of HIV infection. Serious
      questions exist about the ability of these children's families to acquire the
      health care services that both they and their children require. This paper will
      present preliminary findings of a study that describes the physical, behavioral,
      and developmental responses of children who have a diagnosis of perinatally
      acquired HIV, as well as the caretaking concerns of the custodial family.
      Building on this work, a model of transitional home care for these children and
      their families using pediatric clinical nurse specialist (PCNS) follow-up care
      will be described.

PMID- 1393967
TI  - "And the next study in the series is...".

PMID- 1393968
TI  - A comparison of patient/nurse perceptions about current and future recovery
      status.
AB  - Research comparing patient and caregiver perceptions suggests that caregivers
      tend to be negatively biased in their assessment of patients. That is, they are
      more likely to judge the patients' status more negatively than the patients
      themselves. The data analyses, however, have not always been as informative about
      the extent of disagreement. Our data on the extent to which patients who had a
      myocardial infarction and their nurses' assessments differed suggest that, in the
      case of the patients' current status, there were no differences in the aggregate
      between patients' and nurses' assessments. Examination of the discrepancies
      between the pairs, however, suggests that in some cases nurses are more negative
      in their assessments than their patients. In the case of beliefs about the
      future, nurses were significantly more negative, in the aggregate, than patients,
      and the extent of this difference is further elaborated in the examination of the
      discrepancies. Nevertheless, with respect to both current and future status, the
      correlations between patients and nurses were low, indicating little, if any,
      shared variation. Because this study did not examine the relationship between
      either patients' or nurses' perceptions of recovery status, and the patients'
      actual recovery status, further research is needed to further determine the
      implications of this work. The meaning of these results for clinical nurse
      specialists (CNS) is discussed.

PMID- 1393969
TI  - Living on a good compliment.

PMID- 1393970
TI  - A strategy for staff development: self-care and self-esteem as necessary
      partners.
AB  - Using an inservice education approach, the clinical nurse specialist can play an
      important role in the development of nursing staff. This article presents 10 self
      care strategies (valuing strategies) that, if integrated into a nurse's personal
      and professional life, can increase self-esteem and healthy self-care practices.
      Self-care and self-esteem are described as "necessary partners." These self-care
      strategies can be presented to a variety of nursing groups. Utilizing
      experimental group exercises can enhance the learning for such lifestyle changes.

PMID- 1393971
TI  - Catherine's home visit.
AB  - The following vignette tells the story of a young couple and their newborn son
      whose impoverished circumstances momentarily unnerve a nursing student making her
      first home visit. The story illustrates the transcendant power of a bouquet of
      flowers in a Japanese photograph.

PMID- 1393972
TI  - Should CNSs look at the economic value of their services?

PMID- 1393973
TI  - Costs and benefits of clinical nurse specialists.
AB  - The emphasis on cost containment during the 1980s has given way to a renewed
      interest in the quality of health care services that can be delivered at a
      reasonable cost. In this climate, clinical nurse specialists (CNSs) have an
      excellent opportunity to demonstrate the cost-effectiveness of their work. In
      order to do so, costs and benefits of CNS services must be measured and compared.

PMID- 1393974
TI  - Legislative and regulatory update: priorities for clinical nurse specialists.

PMID- 1393975
TI  - Nursing in patient context.

PMID- 1393976
TI  - Reminiscing therapy: a CNS intervention.
AB  - The role of the clinical nurse specialist (CNS) has expanded over the years. The
      CNS is prepared through education and training with group process to initiate and
      implement a reminiscing group for the elderly. Life review and reminiscing are
      dynamic occurrences in which the individual is an active agent. The
      implementation of the program with documentation can be kept simple. A
      nondirective approach may be used to allow the participants to form the group in
      the manner that is most comfortable for them. By using reminiscing techniques,
      the CNS can enhance the quality of the elderly's later years, as well as
      facilitate their last developmental task.

PMID- 1393977
TI  - Laser surgery. Applications and techniques.

PMID- 1393978
TI  - Emergence of lasers in podiatric surgery.
AB  - This article was meant to introduce the reader to the basics of podiatric laser
      use. In a field as complex as laser surgery, it would be impossible to present an
      in depth discussion on any particular area. Instead, the intent was to offer a
      general overview and leave the specifics to the appropriate articles within this
      issue. It is the author's hope that the reader has attained an appreciation for
      the integration of the laser into podiatry. Laser surgery is not proffered as a
      panacea of treatment. Rather, it is an alternative treatment modality that is
      both beneficial and effective within the scope of its indications and
      limitations. As a profession, podiatrists need to cooperate to further define and
      redefine laser usage; as a medical specialty, podiatrists need to participate and
      enhance communication with other medical specialties to help develop more
      advanced laser uses. The uses and indications presented here and elsewhere
      throughout this issue are proven methods of efficacious treatment. It is only the
      unconvincable cynic who could or would deny the established benefits of podiatric
      laser surgery.

PMID- 1393979
TI  - Light, lasers, and beam delivery systems.
AB  - From a clinical standpoint, laser light differs from ordinary light in two
      important ways: (1) laser light, unlike ordinary light, is monochromatic; (2)
      laser light is highly directional, making it possible to efficiently collect and
      focus the light. Laser light is produced through a process known as stimulated
      emission. Tissue effects produced by laser light are governed by the light's
      wavelength. Recently, hollow, flexible fibers have been introduced for CO2 laser
      beam delivery; compared with existing beam delivery systems, the flexible fiber
      provides the clinician with increased tactile sensitivity and effective access
      into restricted spaces.

PMID- 1393980
TI  - Physics of laser beam interactions with living tissue.
AB  - This article examines fundamental laser physics and the manner in which the laser
      transfers energy to the surface of the body and how living cells react. Topics
      include the significance of absorption and scattering coefficients, assumptions
      for analysis of laser-beam interactions with living tissue, depth of vaporization
      of tissue, and mass of tissue vaporized.

PMID- 1393981
TI  - Principles of laser surgery. Advantages and disadvantages.
AB  - An attempt has been made in this article to present an honest and accurate state
      of-art narrative of laser surgery for pedal conditions. The theory of operation,
      physiologic effects and procedural comparisons have been presented regarding
      those procedures and lasers that are available for use by podiatric surgeons and
      others treating the foot and leg. Although some information described within this
      article is anecdotal, it is elaborated with representative expert material from
      the scientific literature. Overall, a sound theoretic understanding of the mode
      of action of lasers and extensive training and experience is encouraged when
      engaging in this exciting discipline of surgery.

PMID- 1393982
TI  - Histopathology of soft tissue lesions of the foot.
AB  - Unfortunately, strict regional considerations of neoplasia affecting the hands of
      feet are not numerous, and detailed accounts of neoplasia confined either to the
      hands or feet have been published only periodically. This article attempts to
      remedy the dearth of information by providing a sampling of the types of tumors
      that affect the foot with photographs and an emphasis on key histologic
      characteristics.

PMID- 1393983
TI  - Lasers in the treatment of skin cancer.

PMID- 1393984
TI  - Carbon dioxide laser excision of benign pedal lesions.
AB  - The CO2 laser is a very important tool to remove benign pedal lesions. It
      certainly is not the only method, but once the technique is developed by the
      surgeon, it becomes easier to remove these lesions and, consequently, the results
      become better. In dealing with the mucoid cysts, the laser surgery is second to
      none and even if it has to be repeated there is basically no disability for the
      patient. This is also true with fibromas because many types of fibromas would
      require suturing that would create an inconvenience for the patient. With the use
      of the laser, sutures are not required and the patients recover much faster. In
      dealing with plantar fibromatosis, ganglionic cysts, and lipomas, the
      convalescence is probably about the same with CO2 laser as with conventional
      removal, especially when deep resection is necessary and suturing of the skin is
      required. With plantar fibromata surgery, the resultant long-term scarring is
      much less with the CO2 laser, especially when followed up with the appropriate
      injectables. CO2 laser surgery performed on the punctata aeriata, interdigital
      clavus formations, and hypertrophic scars are not always as successful but offer
      the surgeon another modality in taking care of the patient's problems without the
      need for extensive surgery.

PMID- 1393985
TI  - Laser onychology.
AB  - Laser techniques for nail pathology have existed for over a decade. Published
      reports concerning onychologic techniques and results are growing along with
      other medical laser literature. In this article, the author has presented
      techniques with which he and podiatric colleagues at Wenske Laser Center have
      operational familiarity. Preoperative concerns have been emphasized and potential
      complications and prevention are discussed. Widely variant results are
      identified. Laser onychologic procedures are technique intensive. Research is
      needed, therefore, to identify factors that might lead to technical improvements
      so that results may be enhanced. Perhaps in the future laser onychology shall
      exist as a subspecialty to podiatry and dermatology, much as endodontics is to
      dentistry. It is hoped that this work might contribute in some small way to that
      development.

PMID- 1393986
TI  - Carbon dioxide laser treatment of pedal verrucae.
AB  - Physicians always are pursuing improved results. In the case of pedal verrucae,
      the varying treatment modalities that have evolved are the product of a search,
      so far less than successful, for one that is virtually 100% effective. HPV is an
      extremely resilient and elusive organism, possessing the capabilities of lying
      dormant and suddenly springing to the surface of the skin. Although no single
      treatment modality has been shown to be a panacea, the authors believe that,
      among the various treatment alternatives available, the CO2 laser offers the best
      surgical prospect for eliminating the verruca and minimizing the sequelae of
      recurrence and postoperative pain.

PMID- 1393987
TI  - Treatment of Morton's neuroma with the carbon dioxide laser.
AB  - Morton's neuroma is one of the most common causes of nerve pain in the foot. This
      article describes the treatment of this condition with carbon dioxide laser
      surgery, presenting the disadvantages and advantages of this method. This method
      has proven to be effective; postoperative pain and healing time are decreased and
      patients are able to resume normal ambulation faster than with conventional
      scalpel surgery.

PMID- 1393988
TI  - Various laser modalities in the treatment of cutaneous lesions.
AB  - This article discusses the various lasers used to treat cutaneous lesions on the
      foot sequentially along the electromagnetic spectrum, beginning with ultraviolet
      lasers and ending with the infrared carbon dioxide laser. Also included is a
      brief history of the use of lasers for cutaneous diseases.

PMID- 1393989
TI  - Management of nucleated plantar keratomas with a carbon dioxide laser.
AB  - Laser enucleation of superficial epidermal keratoses and ablation of dermal and
      subdermal lesions is an effective method for long-term relief from painful
      plantar lesions. This technique also provides gross visualization of the
      remaining tissues, a specimen for microscopic evaluation, and a definitive
      diagnosis. The procedure is relatively atraumatic with a minimal amount of
      postoperative pain, disability and scarring, and a high percentage of acceptable
      results.

PMID- 1393991
TI  - Laser's use in bone and joint surgery.
AB  - The use of various lasers in medicine and surgery has progressed considerably.
      Obviously, the sheer number of lasers being used both clinically and
      experimentally indicates a great potential for further advancement and refinement
      in technique and surgical outcomes. Although the medical field has come very far
      accepting and using the laser, there is still a long way to go.

PMID- 1393990
TI  - The efficacy of carbon dioxide laser surgery for adjunct ulcer therapy.
AB  - This article focuses on the application of the carbon dioxide (CO2) laser at
      various levels of power density to achieve a level of efficacy in tissue ablation
      for cutaneous and deep indolent ulcerations that afflict the lower extremities.
      This article also supports theories of the CO2 laser generating a sterile
      nonpathogenic environment within ulcers. A cross section of various ulcer types
      are used to determine duration of healing.

PMID- 1393993
TI  - Laser treatment of hypertrophic synovitis.
AB  - Hypertrophic synovitis is fairly common in the foot and ankle as a result of an
      injury or in reaction to silicone implants. Laser treatment of this condition is
      accomplished in conjunction with standard surgical techniques. The advantages of
      this method are clear: hemostasis, reduction of postoperative edema, less scar
      tissue, and the potential for reduced postoperative pain.

PMID- 1393992
TI  - Carbon dioxide laser studies of defects in articular cartilage.
AB  - With this further refinement, the author and colleagues hope to establish a
      reliable method of calculating the depth of penetration necessary to induce a
      deficit that will cause chondrogenesis in a predictable, reliable fashion. It is
      hoped that this will allow for consistent results so this technique may be used
      for the treatment of cartilage degeneration and certain arthritides. In addition,
      it is hoped that the fibrous cartilage regenerated from the experiments with
      animals will produce viable information that will lead to extensive human
      applications in the near future. The author also hopes that many joint
      destructive procedures such as arthroplasties and some implant procedures may be
      eliminated, and that this investigation will lead to advances that will eliminate
      much of the morbidity of arthritis.

PMID- 1393994
TI  - Complications of laser surgery: safety, risks, and the plume.
AB  - The prevalence of the CO2 laser in medicine today has brought more information to
      the patient than any other modality to treat different ailments. More laser
      surgeons are reporting their experiences. Like any new instrument or technique,
      there are advantages and disadvantages to its use. This article presented a
      review of different laser-associated problems and issues, as well as methods to
      correct them if they arise. The knowledge of complications and safety are
      constant changing. The surgeon needs to know what can happen, both good and bad,
      in order to inform and treat the patient properly. Although the laser has been
      used in podiatry for the past decade, it can still be considered to be in its
      infancy. It is a wonderful tool for patient care, but more research and
      experience are necessary to use it to its maximal potential.

PMID- 1393995
TI  - Surgery of the achilles tendon and posterior muscle group.
AB  - Ankle equinus is defined as an inability to dorsiflex the foot at the ankle a
      minimum of 10 degrees with the knee in full extension. Numerous causes have been
      presented, and proper evaluation and diagnosis is critical before a surgical
      procedure can be selected. Gross spastic contractures will be managed differently
      than the more subtle forms of limitation of ankle dorsiflexion. Lastly, it should
      be remembered that the desired increase in range of motion will be accompanied by
      a decrease in strength of the posterior group, which will vary with the procedure
      and age of the patient.

PMID- 1393997
TI  - Pedal infectious disease associated with acquired immunodeficiency syndrome.
AB  - AIDS is a disease that quickly takes the lives of individuals of all ages and in
      all countries. Therefore, it is the responsibility of podiatrists to recognize
      the primary manifestations of this disease, to take the proper precautions to
      guard against the spread of this disease, to direct attention to areas in need of
      proper diagnosis, and to provide effective treatment to those with the disease
      and to those yet undetected.

PMID- 1393996
TI  - Systemic complications of human immunodeficiency virus infection.
AB  - HIV infection causes a wide spectrum of complications affecting all organ
      systems. These complications may be primary to the direct infection of a specific
      organ system by HIV or secondary to the immunodeficiency associated with HIV
      infection. These complications may be specific to certain stages of HIV
      infection. Selected common complications of HIV infection include pulmonary,
      neurologic, GI, dermatologic, oral, ocular, endocrine, and hematologic
      complications.

PMID- 1393998
TI  - Kaposi's sarcoma in the foot. A retrospective study.
AB  - Kaposi's sarcoma has been found to be present in a significant number of patients
      infected with HIV. A report of 162 cases of biopsied specimens has been presented
      with a review of previous studies. Diagnosis, cause and treatment have been
      discussed, leading to the conclusion that the podiatrist must be well versed in
      his understanding of Kaposi's sarcoma in order to recognize, treat, and alert the
      patient to the diagnosis of AIDS.

PMID- 1393999
TI  - Pharmacologic treatment of the patient with acquired immunodeficiency syndrome.
AB  - A pharmacologic revolution has occurred over the past 10 years with regards to
      antiviral therapy, specifically medications directed against HIV. This plethora
      of new information must be disseminated effectively throughout the medical
      community. HIV infection and its numerous manifestations, both pedal and
      systemic, are challenging and often difficult to treat. The well-informed
      physician will have a distinct advantage with regard to the treatment of the
      patient with AIDS. The information presented here, although transient, represents
      a solid knowledge base, a starting point on which the clinician can build
      effectively.

PMID- 1394000
TI  - Nutrition for the patient with acquired immunodeficiency syndrome.
AB  - Patients with ARC and AIDS develop a variety of symptoms that significantly
      affect their nutritional status. Podiatrists, although not directly involved with
      the intricacies of the nutritional management of people with AIDS, should be
      aware of the effect of the virus on the human body. Investigators are predicting
      that almost 100% of the estimated 12 million HIV-positive persons in the world
      will develop AIDS. By giving people with AIDS nutritional education, not only may
      there be a beneficial response in respect to treatment but it may enhance an
      individual's quality of life and positive self-image.

PMID- 1394001
TI  - Physical therapy for the patient with acquired immunodeficiency syndrome.
AB  - Treatment of HIV-infected patients has come a long way since the not-so-long-ago
      beginning of the AIDS epidemic. Implementation of new drug therapies has
      increased longevity of a patient's life after being diagnosed with the virus.
      Because HIV-related illnesses are consequently becoming more chronic in nature,
      patients commonly experience potentially debilitating CNS, PNS, or
      musculoskeletal problems during the course of the disease. As a result, these
      patients require delicate care from a number of different health care providers.
      A multidisciplinary team approach must be used within the podiatrist's treatment
      regimen. This team must include the physiatrist overseeing the physical
      therapist, to provide complete and optimal care to improve the patient's
      functional independence and quality of life. The conditions associated with HIV
      infection are insidious, slow, and crushing in nature. The medical community can
      help the patient with HIV infection and AIDS remain on his or her feet. By doing
      this, costs, both social and economic, can be lowered. The podiatrist must have a
      strong knowledge of the pathology of AIDS. He or she must use PT along with other
      disciplines: podiatric medicine, orthotic therapy, and general podiatric care. PT
      is effective in treating conditions of the lower extremities that affect the CNS,
      PNS, musculoskeletal system, and, lastly, rheumatologic effects of HIV infection.

PMID- 1394003
TI  - Preventing human immunodeficiency virus transmission in the podiatric practice.
      The role of the podiatric medical assistant.
AB  - Rationales for the design and implementation of infectious disease control
      programs include protecting the health of patients and staff, reducing the risk
      of vulnerability in litigation, and complying with the regulatory environment
      that mandates such programs. The development and implementation of a
      comprehensive infectious disease control program is not a difficult project. The
      Universal Precautions Policy created by the CDC outlines basic recommendations
      for preventing the transmission of HIV. OSHA regulations also provide step-by
      step guidelines that simplify adaptation of the CDC's policy to the podiatric
      medical practice. The execution of an effective infectious disease control
      program can be accomplished by the use of 10 basic protocols for the podiatric
      practice. These protocols provide the basis for policy, training, follow-up, and
      documentation. Design and implementation of this process within a podiatric
      medical practice can reduce dramatically the risk of inadvertent transmission of
      HIV and other blood-borne pathogens.

PMID- 1394002
TI  - Laboratory testing for human immunodeficiency virus.
AB  - Laboratory testing for HIV infection presents a unique set of challenges for the
      podiatric physician. With increasing numbers of HIV-infected patients, the
      physician has the challenge of selecting, evaluating, and identifying the optimal
      testing methods for patients as well as for physicians. Because seroconversion
      can take weeks to occur, the need for specific tests such as antigen and culture
      becomes very important to both patients and physicians.

PMID- 1394004
TI  - Hospital protocol for the patient with acquired immunodeficiency syndrome.
AB  - This article discusses HIV transmission, prevention, and treatment in a hospital
      milieu. In a review of all the literature, minimal research has been done on
      correlating the potency of the virus in terms of transmission with the stage of
      the disease in an HIV-infected patient. It seems logical that the risk of
      transmission will increase when the HIV patient has the full blown disease. This
      might reflect the statistic that 5.3% of all the health care workers infected do
      not have a determinable cause. Yet it has been proven that seroconversion can
      occur after nonparenteral exposure. This is confirmed by a recent CDC update that
      reported seven cases of seroconversion from mucous membrane exposure. More
      extensive study is needed in developing more accurate statistics on the
      cumulative risk of health care workers in specific fields of medicine and
      specific patient communities. Because all the questions on AIDS apparently are
      not even close to being answered, the importance of using universal precautions
      cannot be overstressed. Unfortunately, research and experience have shown that
      compliance in adopting universal precautions is remarkably poor. Training and
      education must begin at the medical school level with reinforcement through
      yearly workshops. Prevention seems to be the only hope at this time. The
      physician's inability to test patients for this virus has only been a deterrent
      in learning about this dreadful epidemic.

PMID- 1394005
TI  - Treatment of patients with acquired immunodeficiency syndrome in a podiatric
      emergency situation.
AB  - All patients should be considered seropositive, and protective measures always
      should be taken. The mainstays of universal precautions are the use of barrier
      techniques and protection from inadvertent sharps exposure. Various studies show
      that emergency room or trauma patients have a higher HIV prevalence than the
      population as a whole. Several studies of health care workers with known
      parenteral and mucous membrane exposure to HIV positive patients indicate that
      the risk of seroconversion is less than 1%. This low percentage, however, should
      not be used to justify nonadherence to universal precautions.

PMID- 1394006
TI  - Human immunodeficiency virus transmission in health care settings. Risks to
      health care workers.
AB  - Taken together, studies of seroconversion, exposure incidents, and compliance
      with Universal Precautions Policy help researchers understand the risks to health
      care workers of occupationally acquired HIV infection. The seroconversion studies
      show that the risk of infection is low (1 in 250) even when the incident is a
      percutaneous exposure to blood from a known HIV-positive patient. When the
      exposure is to blood from a patient whose HIV-status is unknown, or if the
      exposure is not through the skin, or if the exposure is to a body substance other
      than blood, the risk is considerably lower. The studies of exposure incidents
      show that for most health care workers, percutaneous exposures to blood are
      infrequent. Studies of compliance with Universal Precautions Policy show that
      exposure incidents that do occur can be prevented nearly half the time. The risk
      of patient-to-provider transmission of HIV is small but not completely
      negligible. This small risk can be made even smaller by adhering to recommended
      infection control guidelines, but it cannot be eliminated completely. Although
      most health care workers enter the medical field accepting that their work may
      expose them to infectious agents, there is still a desire for risk-free practice.
      Achieving an entirely risk-free practice is probably impossible; it is certainly
      not within reach today. For the foreseeable future, the only reasonable course is
      to fully understand the risks, to enter into practice psychologically prepared to
      accept these risks, and to practice in a way that minimizes exposures without
      compromising patient care.

PMID- 1394007
TI  - Public health considerations of human immunodeficiency virus.
AB  - The full spectrum of HIV infection will touch the lives of millions of Americans.
      All people need to be aware of this health crisis and its implications on their
      own lives and society. Health care providers need to recognize the risks and take
      appropriate precautions. Millions need assessment of their personal behavior that
      may have permitted them to become infected or that may now be exposing them to
      significant risk of infection. Education and counseling are significant factors
      in prevention. It has been estimated that well over 1,200,000 people in the
      United States are presently infected with HIV. Given all of this, podiatrists
      must be a part of the public health team that offers education, prevention, and
      promotes early care to help prevent the spread of HIV infection and to permit
      those infected to have a chance for longer and healthier lives and, when all else
      fails, to be provided with appropriate and compassionate care. Individuals
      practicing in podiatric medicine can expect recommendations in the future that
      include, in addition to the CDC's Universal Precautions Policy, submitting to
      voluntary determination of serostatus for those who perform exposure-prone
      procedures. Practitioners who are HIV infected and perform exposure-prone
      procedures will have to disclose their status to local review panels who will
      determine their practice. Local panels will then monitor HIV-infected
      practitioners for compliance with practice limitations and report those who
      violate limitations or precautions to state licensing boards. Those who serve on
      review panels will be protected from legal challenges.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1394008
TI  - Ethics and acquired immunodeficiency syndrome.
AB  - The integration into daily practice of a fully realized sense of medical ethics
      is one of the greatest possible sources of personal and professional fulfillment.
      It is also, for the profession as a whole, one of the two ultimate claims to
      continuing legitimacy and respect, the other being technical competence. Of these
      two, the greater is excellence in moral commitments. For as the AIDS crisis is
      demonstrating so well, we often lack the requisite knowledge and skills. When
      knowledge and technology are deficient, it is only moral excellence that can
      protect the sacred values and commitments that make and keep our professions all
      that they have been, are, and can become.

PMID- 1394010
TI  - Death, dying, and the patient with acquired immunodeficiency syndrome.
AB  - This article has attempted to provide some insight into the subject of death,
      dying, and the patient with AIDS. Even though the thought of death and dying is
      common, it is a topic that at most times is left unspoken. This is especially
      true in relationship to an illness that, among many, is considered taboo. This
      article has presented the known psychological stages travelled by a terminally
      ill patient, with special emphasis on the unique problems suffered by the patient
      with AIDS, who is often alone and afraid. Only with the support and kindness of
      others will this lone individual be able to live out his life to its fullest, up
      to his dying day.

PMID- 1394009
TI  - The legal aspects of treating and being treated by an individual infected with
      human immunodeficiency virus.
AB  - Since the first AIDS case was reported in 1981, the AIDS epidemic is spreading
      dramatically in the United States. In dealing with the prevention of HIV
      transmission, we need to carefully balance the protection of civil rights that
      may be devastated by the disclosure of HIV-infection and the protection of public
      health against HIV infection in the health care setting. Recognizing the need of
      guidances in this regard, the CDC has issued recommendations regarding the
      prevention of HIV transmission in the health care setting on the basis of
      scientific data. In order to assure the acceptance of CDC guidelines in the
      health care setting, Congress recently passed a law that requires every state to
      institute CDC guidelines or its equivalent within 1 year. It is hoped that this
      requirement will ensure that HIV infection control measures are uniform
      throughout the nations and help HCWs and patients know their legal rights and
      obligations. Most importantly, the law regulating HIV-infection control will from
      now on rely on scientific data rather than on the irrational fear of the general
      public.

PMID- 1394011
TI  - Child psychiatry: an observation.

PMID- 1394012
TI  - Pilot study for the Quebec Child Mental Health survey: Part I. Measurement of
      prevalence estimates among six to 14 year olds.
AB  - A pilot study for a Quebec Child Mental Health Survey was completed in 1990 with
      139 children aged six to 14 years from the general population. Six month
      prevalence estimates for seven disorders were established using DSM-III-R
      criteria alone and in combination with an impairment index related to the
      diagnoses. Prevalence estimates were studied separately for parents and children.
      Each age group (six to 11, 12 to 14) was also studied separately. The impairment
      index, working as a severity scale, lowered prevalence estimates and allowed
      identification of impairing and non impairing diagnoses. Little overlap was found
      between informants.

PMID- 1394013
TI  - Pilot study for the Quebec Child Mental Health Survey: Part II. Correlates of DSM
      III-R criteria among six to 14 year olds.
AB  - A pilot study for a Quebec Child Mental Health Survey was completed in 1990 with
      139 six to 14 year olds from the general population. The following variables,
      which were correlated with child psychopathology, were studied for each age group
      (six to 11 years, 12 to 14 years) and informant (parent, child): child's gender
      and stressful life events, respondent parent's psychiatric illness, family
      structure, parent-child relationships, parents' relationship, socioeconomic
      status, respondent parent's social desirability. Correlations obtained are
      consistent with those found in the literature. Correlations between the parent's
      mental health, parent-child relationships and the children's mental health are
      the most important results of the study.

PMID- 1394014
TI  - Waiting list information strategies for child psychiatry: an intervention and
      measurement approach.
AB  - This paper describes a number of steps we have initiated to study our chronic
      waiting list problems. We describe a program involving monthly data collection
      which has enabled us to document the effectiveness of some strategies and
      predictive variables. During 1989 the data were supplemented with information
      collected by a questionnaire mailed to every other referral. We found that an
      initial response to the questionnaire was a powerful predictor of successfully
      kept first appointments six to 12 months later. The significance of these
      differences, the impact of our tracking procedures and the issues and causes,
      along with some strategies, are discussed.

PMID- 1394015
TI  - A comparison of the cost-effectiveness of day treatment and residential treatment
      for children with severe behaviour problems.
AB  - This study compares the cost of treating 23 children admitted to a residential
      treatment unit in a psychiatric hospital and 23 children admitted to the same
      unit after it was converted to a day treatment program, through a retrospective
      chart review. The two groups were similar in age, gender, diagnosis, severity of
      pathology, family functioning and support, the number of subjects who dropped
      out, and treatment outcome. The average length of stay on the unit dropped from
      19.6 to 6.1 months, and the average cost of treatment per child decreased from
      $61,412 to $9,213 (Canadian dollars, adjusted for inflation). The sharp decrease
      in treatment time with day treatment may be the result of close links with
      community schools and maintaining the child in the family and community. The cost
      savings can be attributed to the shorter hospital stays and the lower operating
      costs of day treatment. Implications of these findings will be discussed with
      respect to health care policy including the need to raise awareness of day
      treatment as a cost-effective alternative to residential hospital treatment.

PMID- 1394016
TI  - Causes of child abuse and neglect.
AB  - This paper is a study of child abuse and neglect from the perspective of the
      child. Generally, the mistreatment of children was associated with "poor care"
      from parents, attributed mainly to immaturity, marital problems, alcohol abuse,
      unemployment, drug abuse and lack of money. Differences in attribution are noted
      between males and females, and some differences are noted by the age of the
      child. When factors other than the causes given by the children were taken into
      account, mistreatment was significantly related to family break-up, as well as
      long-term disinterest and lack of affection from the parents. When the children
      were asked for their "worst experience in life," the most common responses were
      "abuse" "family break-up," and for the juvenile offenders "getting charged with a
      crime."

PMID- 1394017
TI  - [Mother-infant interaction and the origin of self awareness in the nursing
      infant].
AB  - The mother is the principal care-giving partner of the infant and an important
      source for the development of self-awareness and self-esteem. The importance of
      the early relational experiences of the nursing infant with its mother has been
      widely emphasized by the psychoanalytical approach. Through this special
      interaction with the parent, the infant gradually internalized images leading to
      the individuated self and to self-love. The purpose of this paper is to present
      succinctly some of the broad theoretical positions regarding the forming of the
      self in the nursing infant, first within the "classical" psychoanalytical
      current, then under the impact of more recent research in experimental psychology
      which have given rise to new syntheses. Empirically, the capacity for self
      recognition may be observed during early childhood by means of a child's
      reactions in front of the mirror; therefore, the work dealing with this
      phenomenon will be discussed briefly.

PMID- 1394018
TI  - Misdirected attachment behaviour--an unusual outcome of repeated hospitalization?
AB  - This paper describes an infant with multiple congenital anomalies who developed
      an unusual reaction to recurrent hospitalization before age two. After spending
      much of her first year in hospital, she protested strongly whenever she left the
      hospital. We report the evolution and treatment of this patient's misdirected
      attachment behaviour.

PMID- 1394019
TI  - Body image of children and adolescents and its measurement: an overview.
AB  - The lack of a universally accepted definition of body image has impeded our
      understanding of body image disturbances in children and adolescents. This paper
      examines the evolution of body image as a multidimensional construct and the
      difficulties associated with the use of human figure drawing to measure body
      image. Directions for future research are considered.

PMID- 1394020
TI  - The impact of a physically ill parent on adolescents: cross-sectional findings
      from a clinic population.
AB  - The degree to which the physical illness of a parent affects adolescents is
      unknown. This study examines this issue through a cross-sectional survey of
      patients referred consecutively to an adolescent outpatient psychiatry clinic.
      Demographic and clinical data concerning symptoms, diagnosis of major depression,
      peer isolation, and family functioning were collected on all subjects from both
      the adolescent and a parent (usually the mother). No significant differences were
      found between the groups on measures of family functioning, peer isolation and
      major depression. According to both youth and parent report, adolescents with
      physically ill parents had more somatic symptoms than controls. These findings
      are discussed in the light of the existing literature and the methodological
      shortcomings of the study.

PMID- 1394021
TI  - Substance abuse among adolescents with chronic mental illnesses: a pilot study of
      descriptive and differentiating features.
AB  - Twenty-six adolescents with a chronic mental illness (schizophrenia or
      schizoaffective disorder of at least 1.5 years' duration) were assessed for the
      presence or absence of comorbid substance abuse. The two groups were compared on
      a number of variables believed to identify or predict substance abuse. The
      substance abusing subgroup were significantly different in levels of social
      functioning, school achievement, premorbid substance abuse, having parents or
      siblings who abused substances, dysfunctional families, cigarette smoking, number
      of hospital admissions, and emergency room visits. These findings are discussed
      in the context of clinical issues regarding the management of adolescents with
      chronic mental illnesses.

PMID- 1394022
TI  - Anxiety disorders in children and adolescents: clinical and related issues in
      pharmacological treatment.
AB  - Anxiety disorders in children and adolescents are receiving more attention from
      clinicians and researchers. Psychopharmacological approaches to controlling
      symptoms of anxiety are possible as part of a multi-model treatment approach.
      This paper provides an overview of some recent findings in child and adolescent
      anxiety disorders that may influence treatment decisions. It also reviews studies
      of the use of benzodiazepines and tricyclic antidepressants in treating children
      and adolescents who suffer from anxiety disorders, and suggests methods of
      integrating pharmacological treatment with other modalities in these disorders.

PMID- 1394023
TI  - Child and adult psychiatry: comparison and contrast.
AB  - Since its development from general psychiatry, child psychiatry has been
      influenced by its close involvements with the child guidance movement and
      pediatrics and by the age of its patient population. This has led it to evolve in
      ways quite distinct from adult psychiatry, so much so that at times the
      understanding and relationship between the two disciplines has been somewhat
      strained. This paper relates the development of child psychiatry to its history,
      its tasks and its patient population, highlighting some of the major differences
      between child and adult psychiatry. It then looks at why research in child
      psychiatry has lagged behind research in adult psychiatry. It concludes by
      discussing tensions between the two disciplines, and why it serves the interests
      of both professions as well as those of our patients, that a better understanding
      and collaboration between them be established.

PMID- 1394024
TI  - More research needed into therapeutic family model.

PMID- 1394025
TI  - Use of emergency services justified.

PMID- 1394026
TI  - A double-blind placebo-controlled comparison of moclobemide and amitriptyline in
      the treatment of depression.
AB  - The objective of this study was to determine if moclobemide is an effective
      treatment for depression and if it is well tolerated by patients. A randomized,
      double-blind placebo-controlled trial was conducted in a tertiary ambulatory
      clinic which treats depression. Fifty-five patients participated. They fit the
      DSM-III-R criteria for major depressive episode, scored at least 18 on the 17
      item Hamilton Rating Scale for Depression (HRSD), were between the ages of 18 and
      65, and were not suffering from a major medical illness. After a one week washout
      period, patients were randomly selected to receive placebo, amitriptyline or
      moclobemide for up to six weeks. Moclobemide is a well-tolerated medication at
      therapeutic doses; it is globally as effective as amitriptyline in the treatment
      of major depression.

PMID- 1394027
TI  - The efficacy of reversible monoamine oxidase inhibitors in depressive illness.
AB  - The introduction of selective and reversible inhibitors of MAO-A (RIMA) has led
      to the re-examination of new MAO inhibitors in psychiatry. This paper reviews
      three controlled trials comparing moclobemide with imipramine and clomipramine.
      According to the data presented, moclobemide is as effective as imipramine and
      clomipramine in treating endogenous depression. Moreover, in a comparison with
      clomipramine, in patients with endogenous depression, moclobemide led to an
      earlier improvement in symptoms. A separate trial of moclobemide and clomipramine
      in outpatients with non endogenous depression found a comparable time of onset of
      clinical effect. Patients treated with moclobemide also showed greater tolerance
      after six and 12 weeks of treatment than patients treated with clomipramine. The
      three trials discussed found the RIMA compounds to be free of any serious adverse
      effects and generally better tolerated than the tricyclic compound with which
      they were compared.

PMID- 1394028
TI  - New perspectives on the treatment of depression.

PMID- 1394029
TI  - Depression in the elderly.
AB  - Depression is one of the most common behavioral disorders of later life. Although
      recognition of depression can be difficult and the management of depression in
      elderly patients is complex, effective treatment can dramatically improve their
      quality of life. This brief review presents some of the problems inherent in the
      diagnostic process, reviews the epidemiology of depression in later life, and
      outlines treatment approaches once the diagnosis of depression has been
      established.

PMID- 1394031
TI  - Lip cancer. Incidence trends in Connecticut, 1935-1985.
AB  - Suspicions have recently arisen that cancer of the lip may exert an undue
      influence on overall oral cancer statistics and, therefore, possibly distort the
      true image of intraoral cancer. The authors investigated this question through
      epidemiologic analysis. A total of 2291 cases of lip cancer accessioned by the
      Connecticut Tumor Registry (CTR) from 1935 to 1985 (23.6% of all oral cancer)
      were analyzed. Occurrence trends for males and females had different patterns:
      for men, the age-adjusted incidence rates showed a fivefold decrease during the
      51-year study; for women, the rates were relatively low and constant during the
      same period. Analysis for age-specific rates revealed that the older the age
      group, the higher the incidence rates for both sexes. Squamous cell carcinoma
      accounted for at least 87.4% of all lip cancers (96.2% if nonspecified epithelial
      neoplasms are assumed to be squamous cell carcinoma). The vermilion border of
      lower lip was the most common site. Moderately differentiated tumors were most
      common (48.5%), closely followed by well-differentiated tumors (44.2%). Analysis
      by county showed that the crude incidence rates for males in New London and
      Windham counties exceeded the average Connecticut statewide rates. The authors
      concluded that the epidemiology of Connecticut lip cancer differs significantly
      from that of intraoral squamous cell carcinoma in the same population studied
      within the same period of time. Epidemiologic studies involving "oral cancer"
      should direct attention to anatomic subsite to consider differences in disease
      trends according to specific location.

PMID- 1394030
TI  - RIMA: a safe concept in the treatment of depression with moclobemide.
AB  - Moclobemide--a new, safer antidepressant drug--is described and clinical studies
      are reviewed. Moclobemide represents a new class of drug, the so-called RIMA
      compounds--reversible inhibitors of MAO-A. Unlike classical monoamine oxidase
      (MAO) inhibitors, moclobemide is devoid of hepatotoxicity and has only a slight
      potentiating effect on the hypertensive action of tyramine; treatment does not
      require a tyramine-restricted diet. Studies comparing moclobemide with tricyclic
      antidepressants (TCAs) indicate that moclobemide is significantly better
      tolerated than TCAs and slightly less well tolerated than placebo.

PMID- 1394032
TI  - Flow cytometric DNA analysis of gastric smooth muscle tumors.
AB  - BACKGROUND: To better understand the malignant grade of gastric smooth muscle
      tumors, the DNA content of these tumors was studied. METHODS: In 43 patients with
      gastric smooth muscle tumors, the cellular DNA content was determined by flow
      cytometry and compared with the histologic classification and the prognosis.
      RESULTS: Flow cytometry indicated that all 21 leiomyomas and 9 of the 10 low
      grade leiomyosarcomas were diploid; 10 of the 12 high-grade leiomyosarcomas were
      aneuploid. All patients with leiomyomas and 8 of the 11 patients with diploid
      leiomyosarcomas had neither local recurrence nor metastasis. By contrast, 8 of
      the 10 patients with aneuploid leiomyosarcomas died of their disease (mean
      survival, 41 months; range, 18-78 months). CONCLUSIONS: These results indicate
      that the DNA ploidy pattern shown by flow cytometry is related closely to the
      histologic classification and prognosis of gastric smooth muscle tumors.

PMID- 1394033
TI  - Association of aneuploidy in index adenomas with metachronous colorectal adenoma
      development and a comparison.
AB  - BACKGROUND: Features of index adenomas in the colorectum may be important for the
      prediction of metachronous adenoma development. METHODS: Complete colonoscopic
      follow-up for a mean period of 10 years was achieved in 70 of 124 patients after
      endoscopic polypectomy of an adenoma from the colorectum. On the basis of the
      clinical outcome, the patients were divided into three groups: Group I, patients
      who had a colorectum free of adenomas and cancer; Group II, patients who had one
      or more metachronous adenomatous polyps; and Group III, patients who subsequently
      had a colorectal carcinoma. The clinical characteristics of the patients were
      collected, and the neoplastic specimens were re-examined with regard to
      pathologic parameters and flow cytometrically determined nuclear DNA content.
      RESULTS: Aneuploid stemlines were found in 35% of the index adenomas.
      Significantly more aneuploid adenomas were found in the index adenomas of Group I
      patients than in the adenomas of Group II patients (r = -0.20; P = 0.05).
      However, in the index adenomas of Group II patients, aneuploidy was associated
      with villous architecture (P < 0.05) and inversely related to cellular atypia (P
      < 0.05). Such relations were not found in the adenomas from Group I. In addition,
      in the Group II adenomas, aneuploidy was found frequently in the more proximally
      localized adenomas in the large intestine. Remarkably, all adenocarcinomas of the
      Group III patients were localized in the right colon. No significant differences
      were found in ploidy and mean DNA index between index adenomas and metachronous
      adenomas of the Group II patients. However, the ploidy class of the index
      adenomas was found not to be related to that of the metachronous adenomas in the
      individual patients. CONCLUSIONS: These results demonstrate that DNA cytometry in
      adenomas alone is not helpful in the prediction of the possibility of the
      development of a metachronous adenoma. However, aneuploidy in a villous adenoma
      located more proximally in the colon might indicate a higher risk for
      metachronous neoplasia development. Index and metachronous adenomas are similar
      in DNA content but show no relation with respect to ploidy class.

PMID- 1394034
TI  - The care of patients with colorectal polyps that contain invasive adenocarcinoma.
      Endoscopic polypectomy or colectomy?
AB  - BACKGROUND: The appropriateness of resection in patients from whom polyps with
      invasive adenocarcinoma were excised has been questioned. METHODS: To determine
      the results of this policy, the authors reviewed the outcome of 42 patients from
      whom 44 such polyps were removed. Each polyp was categorized for the level of
      invasion according to the classification of Haggitt. RESULTS: Level 1 invasion
      was found in 27%; level 2, in 9%; level 3, in 11%; level 4, in 39%; and
      uncertain, in 14%. The histologic grade was well differentiated in 48% of
      patients and moderately differentiated in 52%. No polyps contained poorly
      differentiated adenocarcinoma; lymphatic and vascular invasion were not
      encountered. Excision was judged complete in 23 patients; 11 underwent resection,
      and in none was residual adenocarcinoma identified. In 14 patients, margins could
      not be evaluated; of 12 patients who underwent resection, residual adenocarcinoma
      was found in 1. Of the seven patients with positive margins who underwent
      resection, residual adenocarcinoma was found in only two. In the resected
      specimens in which residual carcinoma was encountered, all original lesions were
      designated level 4. None of the patients treated by polypectomy alone has
      experienced a recurrence at a mean follow-up time of 66 months (range, 12-152
      months). CONCLUSIONS: The authors conclude that only patients with level 4
      invasion require resection.

PMID- 1394035
TI  - Serum-ascites albumin concentration gradient and ascites fibronectin in the
      diagnosis of malignant ascites.
AB  - BACKGROUND: The differential diagnosis between malignant and nonmalignant ascites
      by using laboratory parameters has not been completely achieved so far. METHODS:
      The authors studied serum-ascites albumin concentration gradients ([albumin]s -
      [albumin]a), ascites fibronectin and various parameters in 149 consecutive
      patients with ascites (including Group 1: 22 patients with intraabdominal
      malignant lesions; Group 2: 81 patients with chronic liver disease; and Group 3:
      46 patients with hepatocellular carcinoma [HCC]). RESULTS: The concentrations of
      fibronectin, albumin, protein, lactate dehydrogenase, and carcinoembryonic
      antigen in ascites were significantly higher in Group 1 than in Group 2 (P <
      0.001). By contrast, the [albumin]s - [albumin]a was significantly lower in Group
      1 than in Group 2 (P < 0.001). None of these parameters was useful in
      differentiating the ascites of chronic liver disease from that of HCC. In this
      study, to differentiate malignant ascites from the ascites caused by liver
      diseases, [albumin]s - [albumin]a (< 1.5 g/dl) and the fibronectin level in the
      ascites (> 100 micrograms/ml) provided diagnostic accuracy (96.8% and 95.9%,
      respectively) as precise as those of the levels of albumin (> 1.6 g/dl), protein
      (> 2.5 g/dl), and lactate dehydrogenase (> 60 U/l; 97.9%, 96.7%, and 94.8%,
      respectively) in ascites. These results were better than that of carcinoembryonic
      antigen level (> 1.5 ng/ml, 80.9%). CONCLUSIONS: The authors concluded that
      [albumin]s - [albumin]a offered the best method to survey malignant ascites
      because of its sensitivity (100%).

PMID- 1394036
TI  - Coagulation inhibition and activation in pancreatic cancer. Changes during
      progress of disease.
AB  - BACKGROUND: To elucidate the disturbed hemostatic balance in patients with
      pancreatic cancer, the levels of plasma coagulation inhibition and coagulation
      activation were determined. METHODS: Twenty-one patients with adenocarcinoma of
      the pancreas were followed from time of diagnosis until death, using plasma
      analyses of coagulation inhibitors and a molecular marker of coagulation
      activation (thrombin-antithrombin complex, TAT). RESULTS: TAT was increased
      significantly at the time of diagnosis of pancreatic cancer compared with age
      adjusted healthy control subjects (mean, 6.2 +/- 4.6 micrograms/l [standard
      deviation] versus 2.0 +/- 0.7 micrograms/l). It increased with disease
      progression (mean in the terminal phase, 14.1 micrograms/l; P < 0.05). Plasma
      levels of tissue factor pathway inhibitor (TFPI) also were increased
      significantly at the time of diagnosis compared with the control group (mean, 176
      +/- 80% versus 127 +/- 29%; P < 0.05). The TFPI decreased to normal levels (121
      +/- 40%) after surgical removal of the pancreatic tumor (n = 4) or relief of the
      cholestasis using a bypass procedure (n = 6). The TFPI levels increased
      significantly as the malignant disease progressed (from 1-3 months
      postoperatively to the terminal phase of disease; mean, 114 +/- 52% versus 154 +/
      60%). There was a significant positive correlation between TFPI levels and
      bilirubin levels; the correlation coefficient at diagnosis was 0.70 (P < 0.001).
      The levels of the coagulation inhibitors antithrombin, heparin cofactor II,
      protein C, and free protein S decreased significantly with disease progression
      compared with the normal values found at diagnosis. CONCLUSIONS: The mechanism
      for TFPI increase in cancer is not known. It may be related to the preoperative
      cholestasis seen in this study, but the increased degree of coagulation
      activation also may contribute.

PMID- 1394037
TI  - Phase II evaluation of fluorouracil and recombinant alpha-2a-interferon in
      previously untreated patients with pancreatic adenocarcinoma.
AB  - BACKGROUND: Based on initial encouraging results of the combination of 5
      fluorouracil (5-FU) with recombinant alpha-2a-interferon (r alpha-2a-IFN) in the
      treatment of advanced colorectal carcinomas, a clinical trial was conducted using
      5-FU with r alpha-2a-IFN in 49 patients with advanced pancreatic adenocarcinoma.
      METHODS: Forty-nine patients who had bidimensionally measurable disease and had
      not been treated previously with chemotherapy were entered in the trial. Starting
      on day 1, 5-FU was administered as a continuous infusion at a dose of 750
      mg/m2/day for 5 consecutive days. Starting on day 12, it was administered as an
      intravenous bolus of 750 mg/m2 a week for 7 weeks. The r alpha-2a-IFN was
      administered subcutaneously at a dose of 9 x 10(6) units three times a week
      during weeks 1-8. RESULTS: Of the 46 patients evaluable for response, none had a
      complete response, and two had partial responses that lasted 14 and 28 weeks. The
      overall response rate was 4% (95% confidence interval, 1-15%). Fourteen patients
      had minor responses (median duration of response, 12 weeks). The median length of
      survival of all patients enrolled in this trial was 22 weeks. Grade 3-4
      toxicities included oral mucositis in 19 patients, granulocytopenia in 16,
      fatigue in 8, and diarrhea in 3. One patient had severe ataxia and leg weakness.
      Another died of neutropenic sepsis. CONCLUSIONS: This regimen had significant
      toxicity and little evidence of therapeutic activity against advanced pancreatic
      carcinoma.

PMID- 1394038
TI  - The distribution of epithelial membrane antigen in thymic epithelial neoplasms.
AB  - Thymic carcinomas arising within a thymoma have been reported, but the
      relationship between thymoma and thymic carcinoma is poorly understood.
      Epithelial membrane antigen (EMA) is known to be an effective marker for
      establishing the epithelial nature of neoplastic cells, and it is reported that
      staining of tumors is clearly related to the degree of tumor differentiation.
      Eighty-one thymomas (59 noninvasive, 22 invasive) and 14 thymic carcinomas were
      studied immunohistologically using antiepithelial membrane antigen (anti-EMA)
      monoclonal antibody. Thymic carcinomas tended to express much larger quantities
      of EMA than thymomas, and instances of EMA-positive thymoma were seen
      significantly more often in invasive thymomas than in noninvasive ones (P <
      0.05). However, EMA positivity was also associated with gland-like structures,
      which were not necessarily associated with malignant disease. Nevertheless, in
      view of the concept that thymoma and thymic carcinoma show a similar cellular
      differentiation, EMA-positive epithelial cells in thymoma with no relation to
      gland-like configurations might represent a pool of cells having a latent
      potential for malignant disease and might be transformed into thymic carcinoma
      cells under certain conditions. Immunolabeling for EMA appears to be a useful
      tool for determining the degree of malignant disease among thymic epithelial
      neoplasms.

PMID- 1394039
TI  - Evidence for an association between hairy cell leukemia and renal cell and
      colorectal carcinoma.
AB  - BACKGROUND: Hairy cell leukemia (HCL) has been associated with several disease
      states. In this study, a possible association is reported between HCL and renal
      cell carcinoma (RCC) and colorectal carcinoma (CRC). METHODS: A retrospective
      study of the case records of 50 patients with HCL in a study of alpha-interferon
      (alpha-IFN) treatment of HCL. RESULTS: Three of 50 patients with HCL studied had
      RCC, and 2 of these also had CRC. In addition, two other patients had CRC. The
      other malignant lesions developed either before or after the diagnosis of HCL. In
      all patients, the HCL responded to alpha-interferon (alpha-IFN), but in four
      patients, the second lesion was diagnosed during IFN treatment. CONCLUSIONS:
      These findings could indicate that IFN does not correct a possible common basic
      etiologic defect and shows that even early CRC and RCC do not respond to the IFN
      doses administered. These findings should be considered in future trials of IFN
      treatment of these diseases. The authors also recommend a reevaluation of the
      frequency of second malignant lesions in HCL; this may be important particularly
      with the increased survival in patients with HCL who receive alpha-IFN treatment.

PMID- 1394040
TI  - Increased secretion of interleukin-6 in malignant mesothelioma cells from a
      patient with marked thrombocytosis.
AB  - BACKGROUND: A high prevalence of thrombocytosis in malignant mesothelioma has
      been reported, although its pathogenesis remains unknown. METHODS: The case of a
      patient with marked thrombocytosis in peritoneal malignant mesothelioma is
      reported. To investigate the cytokines responsible for thrombocytosis in this
      patient, enzyme-linked immunosorbent assay and immunohistochemical analysis were
      used. RESULTS: Tumor cells produced large amounts of interleukin-6 (IL-6) and
      small amounts of granulocyte macrophage colony stimulating factor (GM-CSF) and
      monocyte colony stimulating factor (M-CSF). Immunocytochemical staining of tumor
      cells showed strong positivity for IL-6. CONCLUSIONS: These results indicated
      that persistent secretion of IL-6 promoted thrombogenesis in this patient.

PMID- 1394041
TI  - Microinvasive carcinoma of the cervix.
AB  - BACKGROUND: Microinvasive carcinoma of the cervix (MIC) has been poorly defined
      in the past and is still a focus of persistent controversy. In 1985, the
      International Federation of Gynecology and Obstetrics (FIGO) defined Stage IA as
      "preclinical invasive carcinoma, diagnosed by microscopy only," subdividing it
      into Stage IA1 or "minimal microscopic stromal invasion," and Stage IA2 or "tumor
      with invasive component 5 mm or less in depth taken from the base of the
      epithelium and 7 mm or less in horizontal spread." In 1974, the Society of
      Gynecologic Oncologists (SGO) defined MIC as any lesion with a depth of invasion
      of 3 mm or less from the base of the epithelium, without lymphatic or vascular
      space invasion. METHODS: To assess the risk of lymph node metastasis and
      treatment failures, pathologic material and clinical data on 370 patients with
      Stage I carcinoma of the cervix, who were treated by radical hysterectomy and
      pelvic-aortic node dissection, were reviewed. Histopathologic analysis of tumors
      was based on a uniform format, including measurement of the maximum depth of
      invasion, the width and length of the horizontal tumor spread, invasive growth
      pattern, cell type, tumor grade, and lymphatic or vascular space involvement.
      RESULTS: Of the 370 patients, 110 had a depth of invasion of 5 mm or less. Of
      these, 54 patients fulfilled the SGO definition of MIC; 42, the new FIGO Stage
      IA2 definition; and 27, both definitions. None of the patients with MIC, as
      defined by either the SGO or the new FIGO Stage IA2, had lymph node metastases or
      tumor recurrence. These data support the conclusion that MIC, defined by either
      the SGO or FIGO definitions, have a low risk for lymph node metastasis or
      recurrent carcinoma. A review of the literature indicated a recurrence rate for
      Stage IA2 of 4.2%. In addition to depth of invasion, lymph vascular space
      invasion is a better predictor of lymph node metastasis and recurrence than the
      surface dimension. CONCLUSIONS: The authors recommend adoption of the SGO
      definition of MIC. Patients with a depth of invasion of 3 mm or less without
      lymph vascular space invasion safely can be treated conservatively.

PMID- 1394042
TI  - Radical surgical procedure improves survival time in patients with recurrent
      ovarian cancer.
AB  - BACKGROUND: There is plenty of evidence that survival time associated with
      advanced ovarian cancer is predominantly related to the amount of residual tumor
      after primary operation. However, there are only few and inconclusive reports
      concerning the effect of second debulking procedures on survival time after
      relapse. METHODS: To evaluate the effect of radical second operation, 30 patients
      with clinically diagnosed relapses had second operations after a median
      recurrence-free interval of 16 months. Considerable efforts were made to resect
      all tumor tissue. Complete resection was achieved in 14 of 39 (47%) patients, and
      residual tumors smaller than 2 cm remained in 12 (40%) patients. In 19 (63%)
      patients, intestinal resections were necessary. Operation time, blood units
      needed, hospital stay, and complication rates were comparable to those associated
      with primary debulking procedures. RESULTS: Survival time after second operation
      was closely correlated with the residual tumor remaining after second surgical
      procedure and also with the length of the recurrence-free interval. Patients with
      complete resections had significantly longer survival times than those with
      residual tumors of less than 2 cm (median, 29 months versus 9 months; P = 0.004).
      Patients with a recurrence-free interval of more than 12 months had a longer
      survival time than those with a shorter disease-free time (median, 29 months
      versus 8 months; P = 0.002). Postoperative treatment also was shown to influence
      survival time, whereas grade of the tumor (P = 0.74), age of the patient (P =
      0.87), and initial FIGO stage (P = 0.58) had no influence on survival time after
      second operation. Multivariate analysis (Cox regression) revealed that residual
      tumor after second surgical procedure (relative risk, 4.7) was the most important
      independent variable predicting survival time after second surgical procedure.
      Recurrence-free interval (relative risk, 2.7) and postoperative (second-line)
      treatment (relative risk, 3.0) were equally potent variables. Residual tumor
      after primary operation, was almost significant (P = 0.06) in the univariate
      analysis, but was canceled in the multivariate setting by the recurrence-free
      interval. Again, FIGO stage, grade of the tumor, and patient age had no
      predictive value. CONCLUSIONS: The authors conclude that radical surgical
      procedure can prolong survival times in patients with recurrent ovarian cancer.
      Patients who had a complete resection of cancer tissue in the primary operation
      or those who experienced a disease-free interval of more than 12 months after
      primary operation are most likely to benefit from second operation in recurrent
      ovarian cancer. Radical surgical procedure should be offered to these patients to
      enhance efficacy of second-line chemotherapy, which is of limited value in bulky
      recurrent disease.

PMID- 1394043
TI  - Fibronectin is an immunosuppressive substance associated with epithelial ovarian
      cancer.
AB  - BACKGROUND: Although the ascites of patients with ovarian cancer has been
      reported to contain immunosuppressive factors, the identity and source of this
      activity has not been determined. Previously, the authors showed that conditioned
      media from two of four epithelial ovarian cancer cell lines inhibits
      proliferation of mitogen-stimulated human lymphocytes. The physical
      characteristics of the inhibitory substance are unlike those of peptide growth
      factors but closely resemble those of fibronectin. METHODS AND RESULTS: In the
      current study, it was found that the two ovarian cancer cell lines that produce
      the inhibitory substance have more fibronectin on the cell surface and secrete
      significantly more immunoreactive fibronectin into their culture media than the
      other two ovarian cancer cell lines. In addition, the immunosuppressive activity
      was bound to a gelatin-Sepharose affinity column, known to bind fibronectin.
      Finally, in ascites from 20 patients with advanced epithelial ovarian cancer,
      fibronectin levels correlated with the ability to inhibit proliferation of lectin
      stimulated lymphocytes (P < 0.001). CONCLUSIONS: Fibronectin is produced by some
      ovarian cancer cell lines and acts to inhibit proliferation of mitogen-stimulated
      lymphocytes. Additional studies are needed to clarify the role of fibronectin in
      ovarian cancer.

PMID- 1394044
TI  - Adenocarcinoma of the prostate presenting initially as an intracerebral tumor.
AB  - BACKGROUND: The authors report a patient who was admitted to the hospital with
      neurologic symptoms and signs that were thought to be caused by a primary
      intracranial tumor. METHODS: Craniotomy resulted in successful resection of an
      occipital lobe tumor reported histologically as a papillary adenocarcinoma,
      probably metastatic from the kidney. However, a complete diagnostic study failed
      to demonstrate the primary focus. RESULTS AND CONCLUSIONS: Thirteen months later,
      the patient was readmitted to the hospital and found to have metastatic prostatic
      carcinoma. Immunoperoxidase staining for prostatic acid phosphatase of the
      prostatic tissue and of the previously resected brain tumor tissue indicated that
      the brain lesion was metastatic from the prostate.

PMID- 1394045
TI  - Black versus white racial differences in clinical stage at diagnosis and
      treatment of prostatic cancer in Connecticut.
AB  - BACKGROUND: There are few published data on stage-specific prostate cancer
      incidence rates in United States black patients versus white patients, and there
      are no data comparing treatment received by black versus white patients with
      prostate cancer. METHODS: Using data from a population-based cancer registry, the
      proportion of prostate cancers diagnosed in Connecticut from 1985-1988 at each
      clinical stage was examined for blacks and whites, along with stage-specific
      incidence rates. First course of treatment was also examined by clinical stage.
      RESULTS: The proportion of cases diagnosed at the metastatic stage was higher for
      black patients (35.4%) than for white patients (22.1%), and age-specific
      incidence rates for metastatic cancer were 1.5-3.3 times higher for black
      patients. Among localized-stage cases, the distribution of histologic grade (or
      degree of differentiation) did not differ in blacks versus whites, suggesting no
      difference in tumor aggressiveness or potential response to treatment. For
      localized (or A and B)-stage cancers, significantly lower use of prostatectomy in
      blacks versus whites younger than 70 years of age was the only important black
      white difference, which requires confirmation in other studies. Frequency of use
      of hormonal therapy including endocrine surgery (orchiectomy) did not differ
      between black and white patients with pelvic metastases or disseminated disease.
      Comparisons were also made with data on treatment (all races combined) reported
      from the American College of Surgeons' national survey of prostate cancer cases
      diagnosed in 1983. CONCLUSIONS: Earlier detection of prostate cancer in blacks is
      needed to reduce black-white differences in stage at diagnosis and thereby reduce
      overall differences in survival rates. There was little evidence for inequities
      in treatment of prostate cancer for black patients versus white patients in
      Connecticut.

PMID- 1394046
TI  - Pleomorphic granular cell astrocytoma of the pineal gland.
AB  - BACKGROUND: Primary neoplasms of the pineal gland are uncommon. Two patients with
      unusual primary pineal tumors that had similar distinctive histologic features
      are reported. METHODS: The surgically resected neoplastic pineal tissue from
      these patients were examined by light microscopy, immunohistochemistry, and
      electron microscopy and correlated with the patients' clinical course. RESULTS:
      These pineal tumors consisted of a mixture of spindle-shaped cells with
      fibrillated cell processes and many large lipidized and/or granular pleomorphic
      cells, some of which were multinucleated. These two tumors superficially
      resembled pleomorphic xanthoastrocytoma and granular cell tumors of the central
      nervous system. The pleomorphic tumor cells expressed glial fibrillary acidic
      protein and some also produced retinal S-antigen, a marker for retinal
      photoreceptor cells. Long-term follow-up (8 years) on one of these patients
      suggested a relatively "benign" clinical course. CONCLUSIONS: It is possible that
      this newly described tumor may be a distinct subset of pineal gland neoplasias
      with a favorable biologic behavior despite the histologic features that would
      suggest otherwise.

PMID- 1394047
TI  - Postoperative wound infection. A poor prognostic sign for patients with head and
      neck cancer.
AB  - BACKGROUND: The development of a wound infection has been identified as a
      favorable prognostic factor after oncologic surgical procedures. METHODS: The
      authors retrospectively studied the relationship between postoperative wound
      infection, local/regional tumor recurrence, and survival rates in 134 patients
      undergoing therapeutic surgical resection for squamous cell carcinoma of the head
      and neck (SCCHN). RESULTS: The median age was 61 years (range, 25-87 years) with
      most (75%) patients having advanced disease (Stage III or IV). Patients without
      evidence of recurrent disease were followed up for a median time of 34 months
      (range, 24-68 months). Twenty-nine (22%) had local or regional bacterial
      infections develop postoperatively. Recurrence rates were increased (P = 0.008)
      in patients with postoperative wound infections compared with patients who had
      distant infections, e.g., pneumonia or urinary tract infection, or no infection.
      Disease-free survival also was adversely affected (P = 0.04) in this group. Both
      advanced tumor stage and postoperative wound infections were independently
      associated with decreased survival, with odds ratios of 2:3 and 2:4,
      respectively. CONCLUSIONS: These data contrast with other reports in the
      literature of a beneficial effect of postoperative wound infection on outcome.
      These findings suggest a possible relationship between local/regional immune
      function and postoperative infection in patients with SCCHN:

PMID- 1394048
TI  - Protocol for the prevention and treatment of oral sequelae resulting from head
      and neck radiation therapy.
AB  - In addition to the desired antitumor effects, head and neck radiation therapy
      induces damage in normal tissues that may result in oral sequelae such as
      mucositis, hyposalivation, radiation caries, taste loss, trismus, soft-tissue
      necrosis, and osteoradionecrosis. These sequelae may be dose-limiting and have a
      tremendous effect on the patient's quality of life. Current policies to prevent
      these sequelae primarily are based on clinical experience and show great
      diversity. A protocol for the prevention and treatment of oral sequelae resulting
      from head and neck radiation therapy, based on fundamental research and data
      derived from the literature, is presented. The protocol is particularly
      applicable in centers with a dental team. This team should be involved at the
      time of initial diagnosis so that a successful preventive regimen is an integral
      part of the overall cancer treatment regimen.

PMID- 1394049
TI  - Human cytotoxic T-lymphocytes specific for autologous follicular lymphoma
      recognize immunoglobulin in a major histocompatibility complex restricted
      fashion.
AB  - BACKGROUND: Previously, autologous Burkitt lymphoma-specific cytotoxic T
      lymphocytes (CTL) were found to express the gamma and delta T-cell receptor and
      recognize tumor idiotype in a major histocompatibility complex (MHC) unrestricted
      fashion. METHODS: In this study, the authors established autologous CTL lines and
      clones specific for a B-cell follicular lymphoma. RESULTS: These CTL are tumor
      specific and inhibited by antiimmunoglobulin monoclonal antibodies, but unlike
      the Burkitt lymphoma-specific CTL, they are MHC restricted and express the alpha
      and beta T-cell receptor. CONCLUSIONS: These studies suggest that different B
      cell lymphomas can induce CTL of different phenotypes and MHC restriction.

PMID- 1394050
TI  - Image-directed percutaneous biopsy. A comparison of cytologic and histologic
      findings.
AB  - BACKGROUND: Image-directed biopsies may be collected as histologic or cytologic
      specimens. METHODS: In 34 patients, the results of aspiration cytologic
      examination were compared prospectively with core tissue biopsy findings obtained
      and diagnosed independently using the same image-guided procedure. RESULTS:
      Cytologic examination disclosed 22 patients with positive or suspicious findings
      of malignancy; there was one false-suspicious result. Seventeen patients with
      such results were discovered by examining the core biopsy specimens. Cytologic
      findings also were more definitive in diagnosing malignancy. Those in whom an
      immediate interpretation could be done were more likely to have adequate
      cytologic specimens (88%) than those without (62%). One to five passes were done,
      but all 21 patients with definitive findings of either benign or malignant by
      cytologic examination underwent three or fewer passes. The three patients with
      positive biopsy results, but less definitive cytologic findings, all underwent
      only one cytologic pass. CONCLUSIONS: Therefore, it was concluded that cytologic
      examination is more sensitive and definitive than biopsy in diagnosing lesions
      using image guidance. Immediate interpretation and/or multiple passes increase
      the diagnostic yield. However, more than three aspiration cytologic passes appear
      to yield diminishing returns.

PMID- 1394052
TI  - Cardiac malignant lymphoma in acquired immune deficiency syndrome.
AB  - BACKGROUND: Extranodal malignant lymphomas (ML) are known to occur with increased
      frequency in patients with human immunodeficiency virus infection. The authors
      report a 30-year-old man with acquired immune deficiency syndrome (AIDS) with ML
      primarily involving the heart and compare the clinical and pathologic features to
      those of previously reported patients. METHODS: The patient's hospital record was
      reviewed and pertinent clinical data were abstracted. Tissue obtained at autopsy
      was processed for routine light microscopic study and immunohistochemistry. A
      computer-assisted search of the medical literature for patients with malignant
      cardiac lymphoma was performed. RESULTS: The patient's initial signs and symptoms
      were nonspecific, and an abnormal gallium scan suggested pericarditis.
      Clinically, the course was characterized by progressive heart failure. Autopsy
      disclosed a diffuse large cell non-Hodgkin lymphoma of B-cell phenotype with
      massive involvement of the pericardium and extension into the myocardium. A
      literature search revealed 22 patients with cardiac lymphoma associated with
      AIDS. Clinical findings were nonspecific, but rapid progression of cardiac
      dysfunction was common after symptoms appeared. Pathologically, most lymphomas
      were of diffuse aggressive subtypes. CONCLUSIONS: ML of the heart is extremely
      rare but is being encountered with increasing frequency in patients with AIDS.
      The diagnosis should be considered in such patients in whom cardiovascular
      symptoms develop suddenly and progress rapidly.

PMID- 1394051
TI  - Surgical stress impairs natural killer cell programming of tumor for lysis in
      patients with sarcomas and other solid tumors.
AB  - BACKGROUND: Natural killer (NK) cells may provide a first line of defense against
      the metastatic implantation of circulating tumor emboli. Because tumor emboli are
      discharged systemically in patients undergoing solid tumor resection, it is
      important to determine the nature of surgical-stress impairment of perioperative
      NK cell cytotoxic function. METHODS: The authors studied 85 patients undergoing
      surgical resection of solid tumors, most of whom had an abrupt and marked
      decrease in NK cell cytotoxicity that was detectable within 18 hours of surgical
      resection. RESULTS: This impairment was not caused by rapidly emerging suppressor
      cells (measured in autologous effector cell mixing studies) or decreased NK cell
      frequency in the peripheral blood (assessed phenotypically and morphologically).
      Instead, surgical stress exerted a direct "toxic" effect on NK cells that could
      be localized to a specific phase of the NK cell tumor lysis cycle. Tumor binding
      and the first round of tumor lysis were intact postoperatively (measured in
      single-cell assays). However, postbinding programming for lysis was decreased
      sharply after surgery (assessed by calcium pulse assays). In addition, the
      kinetics of lysis and the rate of lytic programming were slower after surgery
      (assayed in target saturation kinetic chromium-51 release tests). CONCLUSIONS:
      These latter defects probably were related to the programming for lysis
      deficiency because postprogramming NK cell maximal recycling capacity was not
      affected by surgical stress.

PMID- 1394053
TI  - Incidence of secondary acute myelogenous leukemia after treatment of childhood
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Recent reports of secondary acute myelogenous leukemia (AML)
      occurring in children previously treated for acute lymphoblastic leukemia (ALL)
      prompted a review of patients with ALL treated at the Dana Farber Cancer
      Institute consortium (DFCI) between 1973 and 1987. Seven hundred fifty-two of 779
      children treated for ALL entered complete remission. The mean follow-up time for
      the 752 patients was 4.4 years. Two children had AML develop 12 and 13 months
      after the diagnosis of ALL, respectively. METHODS: The estimated overall risk of
      secondary AML was calculated for the patient population as instances per 1000
      patient-years of follow-up. This was compared with recent reported cases from
      another institution. RESULTS: The estimated overall risk of secondary AML was
      0.61 instances per 1000 patient-years of follow-up (95% confidence interval:
      0.15, 4.4). The difference between the risk of 0.61 among DFCI patients versus
      previously reported risk of 5.8 among a differently treated group of patients
      with ALL was statistically significant (P = 0.0008). No epipodophyllotoxin was
      used in the patients in the DFCI consortium. In contrast, an epipodophyllotoxin
      was used in 12 of 13 previously reported patients who had secondary AML develop.
      CONCLUSIONS: The authors concluded that the use of epipodophyllotoxins may be
      associated with an increased risk of having secondary AML develop in patients
      with ALL.

PMID- 1394054
TI  - Hodgkin disease survivors at increased risk for problems in psychosocial
      adaptation. The Cancer and Leukemia Group B.
AB  - BACKGROUND: The long-term psychosocial adaptations of 273 survivors of advanced
      Hodgkin disease were assessed to determine the nature and extent of problems
      experienced and to identify those at high risk for maladaptation. METHODS:
      Hodgkin disease survivors were identified who initially had been treated in
      clinical trials within the Cancer and Leukemia Group B from 1966 to 1986, were
      currently disease free, and had completed treatment for a minimum of 1 year. All
      survivors had advanced Hodgkin disease (with disease diagnosed at a mean age of
      28 years). Survivors were at a mean age of 37 years at the time of interview (6.3
      years after treatment completion), and 60% were male. Survivors were interviewed
      over the telephone 7-10 days after questionnaires were mailed to them concerning
      their psychological, social, vocational, and sexual functioning. RESULTS:
      Psychological distress was found to be elevated by one standard deviation (SD)
      above that of healthy subjects on the Brief Symptom Inventory, and 22% met the
      criterion suggested for a psychiatric diagnosis. In addition, the following
      problems were reported by survivors to be a consequence of having had Hodgkin
      disease: denial of life (31%) and health (22%) insurance, sexual problems (37%),
      conditioned nausea in response to reminders of chemotherapy (39%), and a negative
      socioeconomic effect (36%). Survivors found to be at high risk for maladaptation
      were: men earning less than $15,000 per year or who were currently unemployed;
      unmarried individuals; those with serious illnesses since treatment completion;
      and those who were less educated. CONCLUSIONS: These findings suggest that
      including a routine assessment of these factors would help to target survivors in
      need of additional evaluation and treatment.

PMID- 1394055
TI  - Risk factors for cancer of the tongue and the mouth. A case-control study from
      northern Italy.
AB  - BACKGROUND: The role of tobacco and alcohol consumption and the frequency of
      intake of a selected number of indicator foods as causes of cancer were
      investigated in a case-control study conducted in northern Italy. METHODS: One
      hundred two men with cancer of the tongue, 104 patients with cancer of the mouth,
      and 726 control subjects (the latter admitted to the hospital for acute
      nonneoplastic disease without respiratory illness) were interviewed. RESULTS:
      Similarly strong associations were observed with cigarette smoking (odds ratio
      [OR], 10.5 and 11.8 for current smokers versus never smokers in cancer of the
      tongue and mouth, respectively) and alcohol (OR, 3.4 and 3.0 for > or = 60 versus
      < or = 19 drinks/week). The risk conferred by pipe or cigar smoking, although
      based on only 12 smokers who did not smoke cigarettes, seemed, however, to be
      lower for cancer of the tongue (OR, 3.4) than cancer of the mouth (OR, 21.9).
      Selected indicator foods and beverages, including green vegetables, carrots,
      fresh fruits, whole-grain bread and pasta, coffee, and tea also affected the
      cancer risk similarly in the two sites. The beneficial influence of such foods
      and beverages seemed, however, to be more marked for cancer of the mouth than for
      cancer of the tongue. CONCLUSIONS: This study suggested that, although none of
      the differences in the effects between cancer sites was statistically
      significant, tobacco from pipes and cigars and the cleansing effect of some foods
      of plant origin and nonalcoholic beverages may influence the risk of cancer of
      the tongue less strongly than the risk of cancer of the mouth.

PMID- 1394056
TI  - How much brushing is enough for the diagnosis of lung tumors?
AB  - BACKGROUND: Bronchoscopic investigations of lung tumors require high diagnostic
      accuracy. Sometimes the combination of brush biopsy with cytologic and histologic
      examination of forceps-obtained biopsy specimens fails to diagnose tumors.
      Techniques with a minimum risk and low cost when repeated several times could
      increase the efficiency of tumor diagnosis and help to avoid rebronchoscopy.
      METHODS: Repeated brush biopsies were done during one bronchoscopic examination
      in 270 patients with pulmonary neoplasias using a flexible fiberoptic
      bronchoscope guided by radiographic video fluoroscopy. The results of up to five
      brush biopsies were compared for their diagnostic sensitivity. RESULTS: Singly,
      68-77% of the specimens showed malignant findings. With repeated brushing, the
      sensitivity of the diagnostic accuracy increased to 89.6%. In the periphery of
      the bronchial tree, the sensitivity of brush biopsy was slightly lower in
      bronchoscopically invisible tumors. In 222 of 242 (91.7%) patients with positive
      results of brush biopsy, there was agreement in the final typing of tumor
      morphology. CONCLUSION: For routine bronchoscopy, repeated brush biopsy should be
      done to obtain the highest diagnostic yield.

PMID- 1394057
TI  - A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and
      cisplatin for metastatic squamous cell lung carcinoma.
AB  - BACKGROUND: In an effort to confirm the efficacy of mitomycin C against
      metastatic squamous cell lung carcinoma and to compare the efficacy of single
      agent therapy with a combination containing cisplatin, the authors conducted a
      randomized Phase III trial of mitomycin C alone versus mitomycin C, vinblastine,
      and cisplatin (MVP). METHODS: All patients had advanced squamous cell lung
      carcinoma, and survival was the primary end point. There were 133 eligible
      patients who received either mitomycin C alone (n = 64) or MVP (n = 69). The two
      groups were similar with respect to performance score, disease status, age, sex,
      and stage. RESULTS: The major objective response rates were 30% (95% confidence
      interval [CI], 18-41%) and 43% (95% CI, 32-55%) for mitomycin C alone and MVP,
      respectively (P = 0.1). The median time to progression was 83 days for mitomycin
      C alone, compared with 119 days for MVP (P = 0.026). The median survival time was
      114 days for mitomycin C and 163 days for MVP (P = 0.09). The 1-year survival
      rates were equivalent. Myelosuppression was the major toxicity, and there were
      significantly greater leukocyte nadirs with MVP therapy (P < 0.001). CONCLUSION:
      Mitomycin C has antitumor activity against squamous cell lung carcinoma when used
      alone or in combination with MVP. The regimen containing cisplatin had marginally
      increased activity that did not translate into a clinically significant survival
      advantage.

PMID- 1394058
TI  - Neuropsychologic impairment in adult bone marrow transplant candidates.
AB  - BACKGROUND: Long-term cognitive impairment has been reported in adult bone marrow
      transplant (BMT) recipients. However, the degree to which such impairment is
      attributable to the procedure or is a condition existing before BMT is not known.
      METHODS: The presence, nature, and correlates of neuropsychologic impairment were
      investigated in 55 adult BMT candidates, all of whom had a malignant condition.
      Impairment was assessed using a screening battery of standardized
      neuropsychologic tests. RESULTS: Results indicated that: (1) neuropsychologic
      performance was associated with specific disease and treatment risk factors, in
      particular a history of cranial radiation or central nervous system disease
      treated with intrathecal chemotherapy; (2) performance on tests reflecting memory
      or higher cognitive processing was more likely to be impaired; and (3) the risk
      of impairment increased as the number of disease and treatment risk factors for
      cognitive impairment in the patient increased. CONCLUSIONS: It was concluded that
      neuropsychologic impairment occurs in a significant minority of adult patients
      before BMT. Research is necessary to determine the extent to which such
      impairment significantly compromises patients' abilities to: (1) make decisions
      regarding undergoing BMT or participating in research protocols and (2)
      understand and execute self-care behaviors after BMT. More broadly, greater
      attention should be devoted to investigating the presence of long-term
      neuropsychologic impairment in adult patients with cancer.

PMID- 1394059
TI  - Orbital granulocytic sarcomas (myeloid sarcomas) in acute nonlymphocytic
      leukemia.
AB  - In a series of 89 patients with acute leukemia, orbital granulocytic sarcomas
      were observed in 7. All these patients had acute nonlymphocytic leukemia, and
      they were all children. The orbital involvement usually was bilateral, and the
      patients had proptosis, conjunctival hemorrhage, and chemosis. Morphologic,
      cytochemical, and immunophenotypic analyses did not show a predilection for any
      particular myeloid cell type. Two patients had biphenotypic leukemias with
      myeloid components. The ocular manifestations responded well to chemotherapy
      irrespective of the hematologic response.

PMID- 1394060
TI  - Spinal epidural tumor in patients with prostate cancer. Clinical and radiographic
      predictors of response to radiation therapy.
AB  - The authors retrospectively reviewed 50 episodes of spinal epidural tumor that
      occurred in 42 patients with metastatic prostate cancer and were treated with
      external-beam radiation. Treatment response was evaluated in terms of symptoms,
      neurologic status, and, in most cases, reduction of tumor on repeat myelography.
      At the completion of therapy, 92% of treated patients experienced pain relief and
      67% had significant to complete improvement on neurologic examination. Thirty
      days after treatment, repeat myelography was performed in 40 of the 50 cases;
      compared with the initial findings immediately preceding radiation therapy (RT),
      the results of 58% of these studies had normalized completely, results were
      improved in 25%, and the results had not changed in 18%. The presence of a high
      grade compression fracture of the vertebral body was an indicator of poor
      prognosis for tumor response on repeat myelography. The ability of a patient to
      walk before treatment and tumor response on repeat myelography were associated
      significantly with improved outcome of RT and with survival. The authors conclude
      that RT can effectively palliate epidural lesions from metastatic prostate
      cancer. The prognosis for the long-term response to therapy may be indicated by
      pretreatment ambulatory status and posttreatment imaging of the epidural space.

PMID- 1394062
TI  - Soluble interleukin-2 receptor serum levels in mycosis fungoides. Correlation
      with clinical stage.
AB  - BACKGROUND: In a variety of non-Hodgkin lymphomas, a correlation between soluble
      interleukin-2 receptor levels (sIL-2R) and clinical stage is demonstrable. In
      mycosis fungoides (MF), two findings raise the question as to a similar
      correlation: (1) a proportion of tumor cells express IL-2 receptor and (2) sIL-2R
      is detectable in serum. METHODS: sIL-2R were measured in patients with MF (n =
      88) and atopic dermatitis (AD) (n = 14) by the enzyme immunoassay technique.
      Patients with AD served as controls. Cases of MF were classified according to the
      TNM staging classification. RESULTS: Sera of patients with MF with stages III,
      IVa, and IVb showed significantly higher values than those of stage I or II and
      controls. CONCLUSIONS: Although a close and significant correlation was found
      between sIL-2R levels and stage of disease in MF, it is still not clear whether
      elevated sIL-2R levels reflect disease activity or T-cell activation due to
      concomitant immunologic processes.

PMID- 1394061
TI  - Immune-mediated disease as a risk factor for canine lymphoma.
AB  - BACKGROUND: Autoimmune diseases and neoplasia have been associated as occurring
      simultaneously in individuals. This study evaluated the association between the
      simultaneous occurrence of canine lymphoma and various immune-mediated diseases.
      METHODS: The Veterinary Medical Data Program, a national disease data registry
      for veterinary schools, was examined. The following immune-mediated disease
      categories were evaluated: lupus disorders, pemphigus disorders, autoimmune
      polyarthritis, immune-mediated hemolytic anemia, and immune-mediated
      thrombocytopenia. Odds ratios with 99% confidence intervals were calculated for
      the occurrence of lymphoma and each of the immune-mediated disorder categories.
      RESULTS: Only dogs with immune-mediated thrombocytopenia had a statistically
      significantly increased odds ratio (5.61; 99% confidence interval, 4.16-7.57) for
      the occurrence of lymphoma versus the general population. This association still
      was observed for immune-mediated thrombocytopenia when stratified by age, sex,
      and neutering status. CONCLUSION: Dogs with immune-mediated thrombocytopenia had
      a greater occurrence of lymphoma than dogs without immune-mediated
      thrombocytopenia.

PMID- 1394063
TI  - The prognostic value of Ki-67 antigen in non-Hodgkin lymphoma of Waldeyer ring
      and the nasal cavity.
AB  - BACKGROUND: A monoclonal antibody, Ki-67, recognizes an antigen expressed in all
      phases of the cell cycle, except G0, and can be used as a simple histologic
      marker of cell proliferation. To assess the prognostic value of the growth
      fraction in non-Hodgkin lymphoma of Waldeyer ring (W-NHL) and the nasal cavity (N
      NHL), the authors applied Ki-67 immunostaining combined with image analysis on
      such lymphomas. METHODS: The authors studied 29 patients (18 with W-NHL and 11
      with N-NHL), applying Ki-67 to frozen sections. The number of Ki-67-positive
      cells in a unit area (0.044 mm2), as an indicator of proliferative activity, and
      the mean area per Ki-67-positive cell (microns2), as an indicator of DNA content,
      were measured by the image processing system. RESULTS: High-grade lymphomas
      showed a significantly larger number of Ki-67-positive cells than intermediate
      grade lymphomas (102.5 +/- 21.6 in high-grade and 46.8 +/- 8.92 in intermediate
      grade lymphomas, P = 0.03), even when analyzed separately by immunophenotypes. A
      large mean area per Ki-67-positive cell was associated significantly with a T
      cell phenotype (36.3 +/- 7.69 microns2 in T-cell lymphomas and 19.4 +/- 2.33
      microns2 in B-cell lymphomas, P = 0.034) and an unfavorable clinical outcome.
      High proliferative activity, defined as nuclear Ki-67 expression in 2000 or more
      B-cell lymphoma cells and 1000 or more T-cell lymphoma cells in a 1-mm2 area, was
      found to be a strong predictor of poor survival among these patients (P = 0.048
      and P = 0.009, respectively). CONCLUSIONS: Ki-67 immunostaining, combined with
      image analysis, is a novel method for determining a tumor proliferative index
      that provides useful clinical data regarding head and neck lymphomas.

PMID- 1394064
TI  - The future of prognostic factors in outcome prediction for patients with cancer.
AB  - The anatomic description of the extent of tumor spread (tumor staging) assists
      clinical management, facilitates communication among physicians, is an essential
      part of randomized controlled trials, and may help in the counseling patients and
      their families. However, in recent years, additional "prognostic factors" have
      been defined, many of which assess or reflect the biologic behavior of malignant
      neoplasms. Other measures of tumor biochemistry address the natural history of
      neoplastic development and often are included in a discussion of new prognostic
      factors. This review article summarizes current knowledge and thinking related to
      tumor prognostic factors in four areas by providing: (1) a definition and
      principles of anatomic spread of tumor (staging) and some suggestions for
      improvement, (2) a description of some examples of additional factors of
      prognostic significance, (3) some statistical methods to evaluate prognostic
      factors, and (4) an examination of the possible future of summary statements of
      outcome (i.e., prognostic indexes).

PMID- 1394065
TI  - Changing risk groups for malignant mesothelioma.

PMID- 1394066
TI  - Pain in the cognitively impaired elderly.

PMID- 1394067
TI  - Pain and the critically ill.

PMID- 1394068
TI  - Kids' pain. A collaborative approach.

PMID- 1394069
TI  - Assessment and management of pain in infants.

PMID- 1394070
TI  - At home with pain.

PMID- 1394071
TI  - Patient controlled analgesia.

PMID- 1394072
TI  - Working together to control postoperative pain.

PMID- 1394073
TI  - [Patients and solicitude].
AB  - Patients are not only passive and vulnerable beings who need to be cared for.
      They are also autonomous, active and capable of caring for others as well as for
      themselves. In this study, the author has completed lengthy interviews with five
      women in order to identify different types of caring. Complicity-based caring is
      characterized by verbal and nonverbal behavior of patients who are sharing a
      common experience. This type of caring can be encouraged by a third-party who
      brings patients together with similar experiences. Action-oriented caring
      consists of intervening for other patients as an antidote for one's own fear,
      panic and anguish. Solidarity-based caring corresponds with assisting fellow
      patients in finding and maintaining their own identity, pride and dignity. Co
      operative caring can be observed in group-type settings such as the behavior
      observed during support groups or vegetarian cooking classes for cancer patients.
      Self-centred caring refers to the various forms of concern one has for one's
      self. The experience of suffering can determine how caring is expressed. Concern
      can force individuals to examine their way of acting and interacting more
      carefully. Conscious choices are made to avoid empty and exhausting relationships
      and encourage the growth of positive relationships. Paradoxically, this change in
      perspective brings about an open mind and heart. It is at this time that caring
      for healthy individuals appears. Unfortunately, there is very little distinction
      between patients and healthy individuals, but rather sensitive relationships
      between individuals facing difficult life challenges.

PMID- 1394075
TI  - Westray grief.

PMID- 1394074
TI  - [Cohabitation of lucid and non-lucid residents].
AB  - The primary goal of this study was to confirm the appropriateness of an
      experimental model that studied the emotions of a rational client toward living
      with cognitively impaired clients. The second goal was to identify factors
      linking the feelings of health caregivers toward the cohabitation or segregation
      of rational and cognitively impaired couples. The research took place in 19
      Montreal senior citizen homes with 75 beds or more. The senior citizen homes, the
      rational clients and the health caregivers were selected using specific criteria
      and systematic sample selection. Individual interviews with 435 rational clients
      living in cohabitation units were undertaken. In addition, 349 health caregivers
      (nurses, practical nurses and attendants) responded to a questionnaire relating
      to the cohabitation of these couples. It was found that the rational clients
      adjusted well to the model. Four variables reflecting the emotions of 33 per cent
      of the rational partners include: The frequency of uncomfortable feelings related
      to living with the cognitively impaired; their knowledge level about cognitive
      impairment; their distress level relating to the confused/irrational behavior of
      the cognitively impaired; and their perception of the advantages of living with
      the cognitively impaired. The rational clients who had the least understanding of
      cognitive impairment identified that they were more upset by the confused
      client's behavior. They demonstrated uncomfortable feelings toward living with
      confused/irrational clients more frequently, and perceived less advantages
      relating to cohabitating with these clients. Consequently, the rational clients
      were less amenable to cohabitation. The percentage of cognitively impaired
      clients living on the same floor was not identified as a variable.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1394076
TI  - Assault.

PMID- 1394077
TI  - A medical workstation for the evaluation of alternative 3D radiotherapy treatment
      plans.
AB  - A medical workstation for the evaluation of alternative 3D radiotherapy plans is
      described. Our system can simultaneously apply qualitative as well as
      quantitative evaluation methods to as many as three 3D dose distributions. The
      user interface of the workstation has been designed with the demands of radiation
      oncologists in mind. The handling of the large amounts of 3D data (CT data, up to
      three 3D dose distributions, volumes of interest) is assisted by computer
      graphics.

PMID- 1394079
TI  - Image segmentation in digital mammography: comparison of local thresholding and
      region growing algorithms.
AB  - Local thresholding and region-growing algorithms are developed and applied to
      digitized mammograms to quantify the parenchymal densities. The algorithms are
      first evaluated and optimized on phantom images reflecting varying image
      contrast, X-ray exposure conditions, and time-related changes. The difference
      between the segmentation results of the two techniques is less than 6% on the
      phantom images and 11% on the mammograms. The agreement between the computerized
      procedures and a manual one is in the range of 74-98%, depending on the breast
      parenchymal pattern and segmentation algorithm. The results show that
      computerized parenchymal classification of digitized mammograms is possible and
      independent of exposure.

PMID- 1394078
TI  - Variability of the regional cerebral blood flow pattern studied with [11C]
      fluoromethane and position emission tomography (PET).
AB  - The mean regional cerebral blood flow (rCBF) pattern measured with [11C]
      fluoromethane and positron emission tomography (PET) in 26 healthy subjects was
      heterogenous throughout the brain showing the highest rCBF in the medial
      prefrontal cortex and the lowest rCBF in the inferior temporal cortex. Right/left
      asymmetry of the mean rCBF was not significant. The variability of the rCBF
      pattern was assessed by dividing the subjects into one group of naive subjects
      and one group of subjects who had habituated to the scanning procedure. Naive
      subjects had a significantly higher mean rCBF (p less than 0.05) in defined areas
      of the higher order association cortices predominantly in the right cerebral
      hemisphere, but a virtually identical mean rCBF in the primary cortical input and
      output areas. These findings suggest a raised level of mental activity in
      subjects undergoing the first PET measurement.

PMID- 1394080
TI  - Applications of hierarchical image segmentation techniques: aorta segmentation.
AB  - The segmentation of objects from complex images is difficult due to indistinct
      boundaries between objects and similarity of objects. We have used a hierarchical
      segmentation approach to accurately distinguish between objects and identify the
      corresponding boundaries. This approach has been used successfully to extract the
      aorta from transverse magnetic resonance (MR) images of the abdomen. The
      procedure to segment the abdominal aorta involves three progressive steps: aorta
      detection, aorta extraction, and estimation of the aorta wall boundary.
      Comparison of hierarchical segmentation techniques with single-step segmentation
      methods (e.g., region-growing, edge-detection) shows that hierarchical
      segmentation yields more reliable results.

PMID- 1394081
TI  - MRI diagnosis of biceps tendon rupture.
AB  - Distal biceps tendon rupture is a rare injury. While plain radiographs are
      usually not helpful in visualizing the defect, evaluation of the tendon with MRI
      has proven to be useful as it depicts complete anatomic detail of the tendon and
      associated structures. Its multiplanar imaging capability and superior soft
      tissue contrast resolution makes MRI a prime diagnostic tool in the diagnosis of
      tendon disorders. We report a case of complete rupture of the biceps tendon
      diagnosed by MRI.

PMID- 1394082
TI  - Metastatic pineoblastoma via a ventriculoperitoneal shunt: CT demonstration.
AB  - We report the CT findings in a patient with pineoblastoma metastatic to the
      peritoneum via a VP shunt. A large, soft tissue tumor mass was revealed in the
      pelvis with associated peritoneal seeding and ascites. The initial intracranial
      tumor biopsy and later biopsy of metastatic peritoneal tumor demonstrated
      identical tissue diagnostic for pineoblastoma. Patients with intracranial
      malignant neoplasms and VP shunts will be followed during or after treatment with
      MRI brain scans. Periodic CT abdomen scans should be obtained to detect potential
      peritoneal metastases early to allow more effective treatment.

PMID- 1394083
TI  - Massive putaminal-thalamic nontraumatic hemorrhage.
AB  - Fourteen patients developed massive putaminal-thalamic hemorrhage. All patients
      were young black men. They were hypertensive but without chronic hypertensive
      vascular changes. They had been treated with antihypertensive medication for less
      than 3 yr. All patients presented with a prodromal headache beginning 18-30 h
      before the brain hemorrhage. Initial clinical signs were heralded by a change in
      the headache pattern and vomiting. All patients became comatose and hemiplegic
      within 4-12 h. CT showed a hyperdense putaminal-thalamic hemorrhage which was 60
      to 86 mm in maximal diameter. There was marked mass effect with secondary
      intraventricular extension. All patients died within 72 h, despite rapid and
      adequate blood pressure control and maximal medical treatment of cerebral edema
      and increased intracranial pressure.

PMID- 1394084
TI  - Case report: extramedullary plasmacytoma of the larynx.
AB  - A case of extramedullary plasmacytoma of the larynx is presented. The case is
      unique for the extramedullary plasmacytoma's marked extension into the
      mediastinum. The computed tomography (CT) features are described.

PMID- 1394085
TI  - Study on the change of lung lamellar body to lattice tubular myelin by N
      acetylglucosaminidase with special reference to membrane components and calcium.
AB  - The possibility of a role of N-acetylglucosaminidase or beta-galactosidase in the
      morphological change of lung lamellar body to lattice tubular myelin was examined
      in an in vitro incubation study. Electron microscopic observation of the
      incubation product and gas-chromatographic analysis of released sugars during
      incubation were used to understand the mechanism of these enzymes in the change
      of membrane constitution. N-acetylglucosaminidase proved to play a role in
      developing membrane of lamellar body toward lattice tubular structure with the
      support of Ca++. In this process, inositol release was indispensable in the
      modulation of membrane as well as the release of a small amount of N
      acetylglucosamine. However, further reaction of this enzyme caused destruction or
      fusion of lattice-tubular integration with the release of other membrane
      components. Beta-galactosidase played no role in this process.

PMID- 1394086
TI  - Myofibrosarcoma of subcutaneous soft tissue of the cheek.
AB  - A low grade soft tissue sarcoma from the naso-labial fold and designated as
      myofibrosarcoma (sarcoma of myofibroblasts) is described using standard light
      microscopy techniques, immunohistochemistry and electron microscopy. Pink
      fibrillated cytoplasm, regarded as one of the typical histological features of
      leiomyosarcoma, was not obvious but immunostaining for alpha-smooth muscle actin
      was positive suggesting smooth muscle differentiation. By electron microscopy,
      tumour cells contained abundant rough endoplasmic reticulum cisternae and a large
      Golgi body; there were modest but numerous bundles of fine filaments with focal
      densities. A conventional lamina was lacking but the cell surface was
      characterised by fibronexus junctions in which there was a conspicuous
      extracellular, fibronectin-containing fibril, apparently mediating contact
      between cell and matrix. The tumour cells therefore showed myofibroblastic
      differentiation. The cell surfaces showed strong immunoreactivity with an anti
      fibronectin antibody. Myofibrosarcoma is not a widely recognised entity and this
      case is only the 7th example to be documented in detail by means of both
      immunohistochemistry and ultrastructure. The combination of electron microscopy
      for detecting the fibronexus junction and immunostaining for fibronectin at the
      cell periphery is suggested as potentially useful for distinguishing
      myofibrosarcoma from leiomyosarcoma.

PMID- 1394087
TI  - Quantitatively evaluated ultrastructural findings can add to the differential
      diagnosis between keratoacanthoma and well differentiated squamous cell
      carcinoma.
AB  - The differential diagnosis between keratoacanthoma (KA) and well differentiated
      squamous cell carcinoma (WDSCC) is not always easy to perform. Seven cases of KA
      and seven cases of WDSCC have been here analyzed by morphometry on
      ultrastructural sections and compared with normal epidermis. Parameters
      expressing the cohesivity among epithelial cells (numerical and surface density
      of desmosomes; volume density of intercellular space) were significantly
      different in KA and WDSCC, so that they may be useful in differential diagnosis.
      The Authors also questioned the nature of KA, suggesting a continuum between this
      lesion and WDSCC.

PMID- 1394088
TI  - Isolation of plasma membranes, Golgi bodies and mitochondria of Xenopus laevis
      morulae. Identification of plasma membrane proteins.
AB  - Homogenates of Xenopus morulae at the 16-32 cell stage were centrifuged on
      discontinuous sucrose gradients. Isolated fractions were identified by electron
      microscopy (EM) as mitochondria, a fraction enriched in Golgi vesicles, and
      plasma membranes. A special effort was made to prepare plasma membranes free of
      cytoplasmic contaminants. The resulting purified plasma membranes appeared
      morphologically identical to plasma membranes in situ. The external surface is
      covered with a fibrillar coat while vesicles are seen attached to their inner
      surface. O'Farell's method (1975) was used to obtain protein patterns of the
      various fractions on 2-dimensional gel electrophoresis. Each fraction displayed a
      specific pattern. By comparing the different patterns, it was possible to
      identify a group of proteins as belonging to the plasma membrane fractions.
      Labelling of cell surface with sulfo-N-hydroxysuccinimido-biotin together with
      differential extraction of proteins has allowed us to tentatively allocate these
      proteins in different structures of the plasma membrane fractions. The data
      presented in this paper corroborate and extend our ultrastructural studies on
      neogenesis of interblastomeric plasma membranes (Bieliavsky and Geuskens, 1990).

PMID- 1394089
TI  - Age-related quantitative changes in inhibitory axo-somatic synapses on Purkinje
      cells of rat neocerebellum (Crus I and Crus II).
AB  - Morphometric analysis concerning inhibitory axo-somatic synapses on the somata of
      rat Purkinje cells was carried out. The percentage and the absolute cell surface
      area occupied with the synaptic junctions as well as their surface-to-somatic
      volume ratio exhibited significant changes with ageing (from 2 to 24 months). All
      the parameters revealed the smallest value at 2 months and a peak at 9 months;
      then, after a decline towards 12 months, they remained fairly constant until 24
      months. It is suggested that the observed modifications in the synaptic
      parameters of the somata would have some connection with compensatory mechanisms
      for dendritic deafferentation seen with ageing or with the onset and development
      of the reproductive life of the animals.

PMID- 1394090
TI  - Synchronized shift in localization of the Golgi complex and the microtubule
      organizing center in the terminal phase of cytokinesis.
AB  - As mammalian cells enter mitosis, the Golgi complex is disorganized and the
      remnants are dispersed throughout the cytoplasm in the form of a few short
      cisternae and small clusters of vesicles. Once the separation of the chromosomes
      is completed and nuclei reform, stacks of flattened cisternae reappear and a
      united Golgi complex of interphase type starts to be reorganized. This process is
      believed to ensure an approximately equal partitioning of the Golgi complex on
      the daughter cells. Here, the configuration of the Golgi complex and its relation
      to the cytoplasmic microtubule system was studied at the end of cytokinesis using
      synchronized cultures of L929 mouse fibroblasts and rat dermal fibroblasts. One
      hour after the release of the mitotic block, the Golgi complex (visualized
      immunocytochemically with antibodies against mannosidase II) was most frequently
      located on the proximal side of the nucleus as related to the intercellular
      bridge (visualized immunocytochemically with antibodies against tyrosinated alpha
      tubulin). One hour later, it was preferentially found on the distal side of the
      nucleus as related to the intercellular bridge. Immunocytochemical demonstration
      of the radiating pattern of microtubules, and direct demonstration of the
      centrioles using antibodies against detyrosinated or acetylated alpha-tubulin,
      showed that the microtubule organizing center (MTOC) shifted position in a
      similar manner as the Golgi complex. Moreover, double staining with antibodies
      against mannosidase II and tyrosinated alpha-tubulin revealed that the Golgi
      complex and the MTOC codistributed at both times after the release of the mitotic
      block. Electron microscopic analysis confirmed that the reforming Golgi stacks
      first gathered close to the centrosome (a pair of centrioles with associated
      structures, constituting the main MTOC in the cell) on the proximal side of the
      nucleus and that the Golgi stacks and the centrosome were subsequently both
      relocated to the distal side of the nucleus as related to the intercellular
      bridge. Taken together, the findings indicate that the Golgi complex goes through
      a characteristic translocation in the terminal phase of cytokinesis and confirm
      the idea that the cytoplasmic microtubule system plays an important role in the
      organization of this organelle system. A possible function of the shift in
      location of the Golgi complex at the end of cytokinesis could be to direct
      membrane traffic first to the elongating intercellular bridge and thereafter to
      the leading edge as the cells are about to separate and move away from each
      other.

PMID- 1394091
TI  - Subcellular structure of the atrial myocardium of children in cases of atrial
      septal defect.
AB  - In order to study the initial development of myocardial ultrastructural changes
      owing to right atrium volume overload, myocytes have been studied in specimens
      taken from the right atrial wall and auricle of four children aged 1 to 6 years
      with ostium secundum atrial septal defect undergoing cardiac surgery. The younger
      patients (1 to 4-year-old children) we observed did not show diffuse and
      significant myocardial ultrastructural damages. The most significant myocardial
      changes were observed in the 2 older patients (six years old) as we found
      subcellular signs of myocardial hypertrophy such as an increased number of
      mitochondria, increased glycogen inclusions, areas of new sarcomerogenesis and
      nuclei lobulated and variably shaped. Focal degenerative changes, such as rupture
      of mitochondrial cristae and intercellular fibrosis were also noted. These
      changes may be considered as the initial features of myocardial hypertrophy
      because they were not as severe and diffuse as those usually seen in a marked
      functional failure.

PMID- 1394092
TI  - Rickettsiae-like microorganisms in the midgut and other visceral tissues during
      development of Drosophila auraria.
AB  - Rickettsiae-like organisms (RLOs) were identified for the first time in midgut,
      Malpighian tubules, wreath cells (ventral nephrocytes), spermatogonia and gut
      muscles in a species of Drosophila. Their number in the midgut cells of
      Drosophila auraria significantly increased at the late third larval instar and at
      the beginning of pupation. The RLO population in the larval midgut followed the
      fate of their host cells and was destroyed during metamorphosis. The RLOs pass
      from the larval to the adult midgut via the RLOs existing in the 'regenerative
      cells', which will form the adult midgut during population. The total volume of
      RLOs per anterior midgut cell increased analogically in relation to the absolute
      volume of the host cells till the 130 h larval stage. However, during the late
      third instar and at the beginning of pupation the total volume of RLOs per host
      cell significantly increased. The physiological significance of the latter data
      as well as the relationship between RLOs and host cells are discussed.

PMID- 1394093
TI  - Early ultrastructural changes during thioacetamide-induced apoptosis in rat
      liver.
AB  - An histological and ultrastructural study of the early changes in the liver
      following a single administration of thioacetamide (TH), was carried out in male
      Wistar rats. One hour after treatment, apoptosis was already present in the
      liver. By electron microscopy, the following sequential changes were observed:
      progressive detachment of hepatocytes from neighboring cells, formation of
      surface infolds with multiple blebs and, finally, release of several membrane
      bounded apoptotic bodies in the extracellular space and into the sinusoidal
      lumen. Three hours after TH administration, the apoptotic cycle was almost
      entirely completed, as shown by the presence of phagocytosed apoptotic bodies
      inside the cytoplasm of intact liver cells. Our study evidences that TH induces
      apoptosis of liver cell as early as one hour after its administration. Moreover,
      our data show that the apoptotic cycle may be completed in 3-4 h. From the
      morphological point of view, apoptosis induced by TH appears indistinguishable
      from programmed cell death, occurring during embryogenesis or metamorphosis, and
      from apoptotic cell death seen during regression of mitogen-induced rat liver
      hyperplasia.

PMID- 1394094
TI  - Cytochemical characterization of the cuticle of Caenorhabditis elegans (Nematoda:
      Rhabditoidea).
AB  - At the ultrastructural level, the Caenorhabditis elegans (Maupas, 1900; Doughert,
      1953) cuticle shows the presence of six layers: epicuticle, external cortical,
      internal cortical, intermediate, fibrous and basal. Two techniques were used for
      carbohydrate localization: the periodic acid-thiosemicarbazide-silver proteinate
      (Thiery) and gold-labelled lectins. No labelling was found on the nematode's
      cuticle. With the ethanolic phosphotungstic acid technique (E-PTA), that detects
      basic proteins, reaction product was observed in the outer cortical layer, in the
      cuticle struts and in the dense bodies of the muscle cell. Surface anionic sites
      of C. elegans were visualized by using cationized ferritin particles, at pH 7.2,
      and by using colloidal iron hydroxide particles at pH 1.8. Treatments with
      trypsin and neuraminidase (Vibrio cholerae) did not interfere with the binding of
      the cationic particles to the nematode's surface. In contrast, treatment with
      chondroitinase ABC, a specific enzyme for glycosaminoglycans, significantly
      reduced the binding.

PMID- 1394095
TI  - Characterization of four melanoma cell lines with electron microscopy,
      immunocytochemistry, cytogenetics, flow cytometry, and southern analysis.
AB  - Four cell lines established from human metastatic malignant melanoma, derived
      from four patients, were analyzed. Ultrastructurally and immunocytochemically,
      the cultured tumor cells had retained characteristic features of melanocytes and
      of the primary malignant melanomas. The genetic stability was investigated by
      repeated flow-cytometric and cytogenetic analyses over 24 months of continuous
      cultivation. The DNA indices ranged from 1.7 to 2.1 and were stable during the
      entire period. The same was true for the karyotypes, which had modal numbers
      ranging from 50 to 84. The most common types of abnormalities were:
      isochromosomes i(1q), i(9q), translocations (1;17) and (3;6), and other
      aberrations (1p+,4p+,5p+,11p+,11q-,11q+). Abnormalities involving chromosome 1
      were present in all cell lines, but loss of genetic material from chromosome 1p
      was demonstrated in only one of four cell lines when tested by the Southern
      blotting technique using a lambda MS1 probe.

PMID- 1394096
TI  - Karyotype evolution in a patient with biphenotypic neonatal leukemia.
AB  - We present the case of a 4-day-old boy with acute lymphoblastic leukemia showing
      at onset a karyotype 46,XY,t(4;11)(q21;q23). At relapse an additional change,
      add(2), was present. Molecular analysis showed the same immunoglobulin
      rearrangement both at onset and at relapse, but immunohistochemical analysis
      revealed some cells having myeloid features. A continuous cell line derived from
      the leukemic blasts of the patient presented typical monoblastic features.

PMID- 1394097
TI  - Cytogenetic and FISH studies of abnormal X chromosomes in a patient with ANLL.
AB  - We report a case of idic(X)(q13),r(X)(p22q13), and del(X)(:p11-->cen-->q11:) in a
      71-year-old female patient with de novo acute nonlymphocytic leukemia (ANLL), FAB
      M4. The abnormal X chromosomes of this patient were identified cytogenetically by
      G-banding technique and were further confirmed by fluorescence in situ
      hybridization (FISH) using an alpha-satellite probe to chromosome X centromere.
      The features of this are compared with other cases reported in the literature.

PMID- 1394098
TI  - Temporal association of marrow eosinophilia with inversion of chromosome 16 in
      recurrent blast crises of chronic myelogenous leukemia.
AB  - We report a patient with Ph+ chronic myelogenous leukemia (CML) whose recurrent
      blast crises were associated with marrow eosinophilia and inv(16). After
      intensive chemotherapy, for each blast crisis, the patient reentered chronic
      phase with disappearance of both the inv(16) and the eosinophilia.

PMID- 1394099
TI  - Detection of an i(17q) chromosome by fluorescent in situ hybridization with a
      chromosome 17 alpha satellite DNA probe.
AB  - An isochromosome for the long arm of chromosome 17,i(17q), is frequently found as
      an additional chromosome aberration to the Ph with advanced disease in the
      chronic myelocytic leukemia (CML). We studied an i(17q) in blood samples from two
      patients with CML in blast crisis with a biotinylated chromosome 17 specific
      alpha satellite deoxyribonucleic acid probe. G-banded karyotypes of these
      patients showed a dicentric i(17q), dic(17)(p11.2). Fluorescence in situ
      hybridization (FISH) delineated one normal chromosome 17 and one i(17q) among
      metaphase chromosomes; the latter showed a dicentric pattern. In most interphase
      nuclei of both patients, two fluorescence spots were observed. In some interphase
      nuclei, including mature neutrophils, the dicentric chromosome was discernible by
      its size and shape of the fluorescent spots. Three fluorescent spots were
      observed in a small proportion of interphase cells, and existence of a subclone
      with two normal chromosome 17 and an i(17q) was confirmed by examining a large
      number of metaphase plates. The results of FISH provided us with information of
      numerical and structural aberrations of chromosome 17 in interphase cells.

PMID- 1394100
TI  - Significance of trisomy 7 in thyroid tumors.
AB  - Standard cytogenetic studies of a multifocal metastasizing papillary thyroid
      carcinoma revealed two clonal chromosome aberrations: rearranged 10q and trisomy
      7. Trisomy 7 seemed to be restricted to tumor nodule A, whereas era (10q) was
      detected in tumor nodule B and in a metastatic lymph node. We applied fluorescent
      in situ hybridization to ask whether trisomy 7 was a feature of the original
      tumor nodule or an in vitro phenomenon changing quantitatively during early
      passages and to see whether trisomy 7 was restricted to tumor nodule A. We used
      the biotinylated chromosome 7 alpha-satellite probe D7Z1 on freshly dropped
      slides from metaphase harvests from tumor nodule A,B, and the lymph node and on
      touch preparations from the frozen specimen of tumor nodule A. Trisomy 7 was
      present in the original tumor nodule (6% of cells), as well as in early passages
      (P1-3) from both tumor nodules and the metastatic lymph node with a frequency of
      10.7-13.2%. The detection of trisomy 7 as a stable component in short-term cell
      culture and its presence in the original tumor material indicates that this
      common numerical aberration is an in vivo phenomenon.

PMID- 1394101
TI  - Microprocedure for in situ nick translation of chromosomes.
AB  - We have modified the procedure of in situ nick translation to shorten the
      autoradiographic exposure time from 1 month to 3 days and reduce the volume of
      nick translation solution by a factor of at least 10. The modified procedure can
      be carried out on individually chosen chromosome spreads. The procedure was used
      on chromosome spreads of three related lines of mouse mammary epithelium (+SA, 
      SA, CL-S1) with different degrees of tumorigenicity. We found that the
      autoradiographic silver grains that are observed following in situ nick
      translation were often placed at the apparent junction site of chromosome
      translocations or at the breakpoint of chromosomal pieces. We found also that
      silver grains were located above double minute chromosomes, which suggests that
      there are active genes in double minutes.

PMID- 1394102
TI  - Cytogenetic analysis of hematologic malignancies in Hong Kong. A study of 98
      cases.
AB  - The karyotypes of 98 patients between the ages of 8 and 81 years with acute
      lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic
      syndromes (MDS), and chronic myeloid leukemia (CML) are presented. Although the
      well-described cytogenetic abnormalities associated with particular FAB subtypes
      in the West were observed, certain important local differences were noted. In
      ALL, hyperdiploidy was rarely observed, whereas the Philadelphia chromosome was
      observed in 50% of abnormal karyotypes. In AML, the t(8;21) was infrequently
      observed in M2 case, whereas trisomy 4 and 6, rarely reported elsewhere, formed
      12% of the abnormal cases. In MDS, the incidence of -5/5q- and/or -7/7q- was 83%
      of cases with aberrant cytogenetic findings. Neither i(17q) nor an extra Ph was
      seen in 26 cases of CML including 9 cases of accelerated phase/blast crisis. In
      addition, previously unreported cytogenetic abnormalities occurring as single
      cases are presented. These findings are discussed in the context of geographical
      heterogeneity of chromosomal abnormalities in leukemia and emphasize the
      importance of continued epidemiologic studies of cytogenetics in hematologic
      malignancies.

PMID- 1394103
TI  - Longitudinal cytogenetic study of metaphase and interphase cells in childhood
      monosomy 7 syndrome.
AB  - A 15-year-old male with myelodysplastic syndrome (MDS) characterized by monosomy
      7 was cytogenetically evaluated by metaphase karyotyping and fluorescence in situ
      hybridization (FISH) of interphase cells at six different points during the
      course of his disease. At diagnosis, there was complete agreement between
      metaphase and interphase findings. Interphase analysis alone provided important
      cytogenetic information on the first specimens received following intensive
      combination chemotherapy and bone marrow transplantation where metaphase analyses
      were uninformative. The detection of a minor post-treatment monosomy 7 population
      by interphase but not metaphase studies may have identified minimal residual
      disease prior to recurrence of MDS. From this longitudinal study, it is concluded
      that metaphase and interphase cytogenetic analyses form complementary approaches
      and that use of both provides greater analytical power when appropriate
      chromosome markers are available.

PMID- 1394104
TI  - Isolation of a yeast artificial chromosome clone that spans the (12;16)
      translocation breakpoint characteristic of myxoid liposarcoma.
AB  - Cytogenetic analysis of liposarcomas has demonstrated that translocation (12;16)
      (q13.3;p11.2) is characteristic of the myxoid subtype of this adipose tissue
      tumor. Our previous results suggested that the GLI gene is close to the
      translocation breakpoint on chromosome 12. We now describe a yeast artificial
      chromosome (YAC) that contains GLI and spans the chromosome 12 region involved in
      the t(12;16) breakpoint. This clone will permit rapid definition of the genetic
      region surrounding the breakpoint and allow isolation of the gene presumably
      affected by the translocation.

PMID- 1394105
TI  - Interphase cytogenetics on paraffin sections of malignant pleural mesothelioma. A
      comparison to conventional karyotyping and flow cytometric studies.
AB  - We performed in situ hybridization (ISH) studies of malignant pleural
      mesotheliomas to detect numerical aberrations of chromosomes 1 and 7 in
      interphase nuclei of paraffin sections of 13 cases that had been analyzed
      previously by conventional karyotyping and flow cytometry. The hybridizations
      were performed with the biotin-labeled probes recognizing repetitive DNA
      sequences in the (peri)centromeric regions of chromosomes 1 (1q12) and 7(7cen).
      Application of histologic sections allowed us to analyze the tumor cells only.
      Comparison of the karyotype and ISH studies showed that the same chromosome copy
      numbers were detectable by both methods in 13 (chromosome 1) and in 12
      (chromosome 7) cases evaluable by ISH. DNA indexes determined in the paraffin
      embedded tumor material corresponded with the ISH findings. As compared with
      karyotype analysis, ISH showed a larger heterogeneity in chromosome copy numbers.
      The results can be divided into three groups: 1) Monosomy or disomy of
      chromosomes 1 and 7 was detected by both methods in two cases; 2) in four cases,
      disomy of both chromosome 1 and 7 was observed in most of the cells by ISH
      analysis, and karyotype analysis had shown clear polyploidization in three of
      these cases; 3) in seven cases, supernumerary copies of chromosomes 1 and/or 7
      were present in an evident fraction (27-80%) of the cells analyzed by ISH, and
      karyotype analysis confirmed the aberrant copy numbers in five of these cases. On
      the other hand, ISH showed copy numbers not detected by karyotype analysis in six
      of the seven cases. Thus, by combining karyotype and interphase cytogenetic
      studies, complementary information about chromosomal aberrations in mesothelioma
      is obtained.

PMID- 1394106
TI  - Analysis of prostatic tumor cultures using fluorescence in-situ hybridization
      (FISH).
AB  - Analysis of ten primary prostatic tumor cultures using fluorescence in-situ
      hybridization (FISH) with pericentromeric probes for chromosomes 7, 8, 10, 16,
      17, and 18 revealed aneusomies in nine of these specimens. Classical cytogenetics
      by G-banding indicated that only four of those same ten specimens had any (but
      not consistent) clonal abnormalities. This preliminary study suggests that
      aneusomy is a common event in early-stage prostatic tumors, and also supports the
      notion that multiple chromosomes are involved. In combination with routine
      cytogenetic analysis, FISH is thus likely to be a powerful tool in the evaluation
      of prostatic cancer.

PMID- 1394107
TI  - Complex chromosomal rearrangements in an unusual variant of hairy cell leukemia.
AB  - An unusual case of variant HCL with multiple ribosomal lamellar complexes and
      complex chromosomal changes is described. The karyotype of the main cell clone is
      characterized by involvement of chromosome 5 at q13.3 and interstitial deletion
      of 7q. However, there is no other evidence of myelodysplasia and the abnormal
      cells are of lymphoid origin with a B-cell immunophenotype. The clonal
      chromosomal evolution involves rearrangements at sites known to be specifically
      altered in lymphoid tumors.

PMID- 1394108
TI  - t(13q;17p) and del(5q): possibly specific changes in Chinese patients with
      colorectal cancers.
AB  - Cytogenetic study of 18 colorectal carcinomas confirmed the extensive
      heterogeneity and the complexity of the karyotypic picture in this type of tumor.
      Karyotypic analysis showed that chromosomes 17p and 5q, in both numerical and
      structural aspects, were the most frequently involved chromosomes and prone to
      losses. The most common structurally rearranged forms were translocations of 17p
      with other chromosomes, especially t(13q;17p), which constituted over 50% of all
      17p rearrangements, and an interstitial deletion of 5q that made up as much as
      73% of all structural abnormalities of 5q. According to the results, we conclude
      that chromosomes 17 and 5 may play important roles in the evolution of colorectal
      cancer and t(13q;17p) and del(5q) may be possibly specific to Chinese patients
      with colorectal cancer.

PMID- 1394109
TI  - Acute lymphoblastic leukemia of Burkitt type (L3) with a (14;18) and an atypical
      (8;22) translocation.
AB  - A 67-year-old man had night sweats, tumor lysis syndrome, and typical histologic
      and immunophenotypic features of Burkitt-type acute lymphoblastic leukemia (ALL).
      Cytogenetic analysis showed a previously unreported karyotype, a combination of a
      (14;18) and an atypical (8;22) translocation.

PMID- 1394110
TI  - Cytogenetic analysis of a uterine lipoleiomyoma.
AB  - We cytogenetically analyzed a uterine lipoleiomyoma. A primary chromosomal
      abnormality, t(12;14), was found in all 62 cells studied. A secondary change
      involving chromosomes 1 and 5 was detected in 15 of 62 cells. These findings
      suggest that lipoleiomyomas share the same chromosomal abnormalities found in
      common leiomyomas. We speculate that the secondary chromosomal change involving
      chromosomal 5 may be responsible for the lipomatous change.

PMID- 1394111
TI  - Translocation (5;22) in an Askin's tumor.
AB  - A boy with a brain metastasis of an Askin's tumor was investigated. Cytogenetic
      studies revealed a near-diploid karyotype with monosomies of chromosomes 5 and 22
      in the presence of a derivative chromosome der(5)t(5;22)(q35;q11). In particular,
      no involvement of chromosome 11 was seen.

PMID- 1394112
TI  - Trisomy 13 in a case of acute promyelocytic leukemia.

PMID- 1394113
TI  - Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue.

PMID- 1394114
TI  - Antimutagenic effects of polyphenolic compounds.
AB  - Smokers expose themselves to potent carcinogens daily. One of them is the
      nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK). Since estimates are that humans consume 1 g of phenolic compounds/day, we
      investigated the inhibitory effects of five structurally related polyphenolic
      compounds on the mutagenicity of NNK in Salmonella typhimurium TA1535. NNK at a
      concentration of 80 mM was activated by hamster liver microsomes. The
      antimutagenic efficacies were dose-related between the non-toxic concentrations
      of 0.1 and 0.5 mmol/dish in the following order: esculetin > ellagic acid > (+)
      catechin > propyl gallate > (-)esculin. At the highest non-toxic dose tested (0.5
      mmol/dish), these polyphenolics inhibited mutagenesis in TA1535 by 77%, 67%, 62%,
      59% and 53%, respectively. The results of this study demonstrated that
      polyphenolic compounds may inhibit the activation of NNK.

PMID- 1394115
TI  - Reversal of aflatoxin induced liver damage by turmeric and curcumin.
AB  - The effect of certain food additives on aflatoxin production by Aspergillus
      parasiticus has been studied in vitro. Extracts of turmeric (Curcuma longa),
      garlic (Allium sativum) and asafoetida (Ferula asafoetida) inhibited the
      aflatoxin production considerably (more than 90%) at concentrations of 5-10
      mg/ml. Similar results were also seen using butylated hydroxytoluene, butylated
      hydroxyanisole and ellagic acid at concentration 0.1 mM. Curcumin, the
      antioxidant principle from Curcuma longa did not have any effect on aflatoxin
      production. Turmeric and curcumin were also found to reverse the aflatoxin
      induced liver damage produced by feeding aflatoxin B1 (AFB1) (5 micrograms/day
      per 14 days) to ducklings. Fatty changes, necrosis and biliary hyperplasia
      produced by AFB1 were considerably reversed by these food additives.

PMID- 1394116
TI  - Immunological mechanism of action of the tumor reducing peptide from mistletoe
      extract (NSC 635089) cellular proliferation.
AB  - A peptide isolated from the Viscum album extract (Iscador) has been reported
      earlier to the both cytotoxic and tumour reducing. Spleen cells from animals
      treated with a very small quantity of this peptide were found to have increased
      response to phytohaemagglutinin and Concanavalin-A, indicating that more mature
      lymphocytes are produced by the peptide administration. Moreover injection of the
      peptide at the lesion site produced infiltration of lymphocytes and macrophages
      and finally producing necrosis of the tumor. This peptide also stimulated
      macrophages in vitro and in vivo and activated macrophages were found to have
      cytotoxic activity towards L-929 fibroblasts.

PMID- 1394117
TI  - TGF-alpha and IGF-I effects on calcium ion transients in human breast cancer
      cells.
AB  - In order to evaluate the potential role of calcium as an intracellular messenger
      for IGF-I and TGF-alpha action on breast cancer cell proliferation, we determined
      whether these growth factors induce any change in [Ca2+]i using fura-2 loaded
      cells. The hormone independent BT-20 and MDA-MB-231 cells were refractory to the
      mitogenic actions of exogenously added IGF-I and TGF-alpha. TGF-alpha
      administration, however, stimulated [Ca2+]i transients in the BT-20 cells. IGF-I
      and TGF-alpha stimulated DNA synthesis in the MCF-7 and T47D cells. These growth
      factors did not, however, stimulate any changes in [Ca2+]i in these cells. These
      data support the idea that receptor-mediated phospholipid hydrolysis does not
      serve a major signalling function for driving human breast cancer cells into DNA
      synthesis.

PMID- 1394118
TI  - Differential inhibition by staurosporine of phorbol ester, bryostatin and okadaic
      acid effects on mouse skin.
AB  - The tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA), a strong
      activator of protein kinase C (PKC) and okadaic acid, which is ineffective in
      this respect, induce a rapidly developing ('early') edema of the mouse ear.
      Bryostatin, another potent activator of PKC, is unable to induce an 'early' edema
      but causes a more delayed development of edema at a time when most of the PKC is
      down-regulated. The PKC inhibitor staurosporine neither inhibits the early TPA-
      nor the late bryostatin-induced edema, but suppresses the okadaic acid-induced
      edema very effectively. TPA as well as bryostatin, but not okadaic acid cause a
      down-regulation of PKC, which is not inhibited by staurosporine. The calmodulin
      antagonist cyclosporine A, which does not suppress PKC activity, very effectively
      inhibits the TPA-induced edema and down regulation of PKC. Hence we conclude that
      protein phosphorylation catalyzed by staurosporine-suppressable PKC is not
      involved in the induction of edema and PKC down-regulation by TPA but that a
      calmodulin dependent process may play a critical role in these and other TPA
      effects in mouse skin.

PMID- 1394119
TI  - Promoting effects of 6-mercaptopurine on carcinogenesis in various organs of F344
      rats.
AB  - Possible promoting effects of 6-mercaptopurine (6-MP) on carcinogenesis in
      various organs, including the hematopoietic system, were investigated in female
      F344 rats, using a 2-stage carcinogenesis model. 6-MP was given as a dietary
      supplement (50 ppm) for 35 weeks subsequent to wide-spectrum initiation with N
      ethyl-N-nitrosourea (ENU). Various tumors were observed in the carcinogen
      initiated groups. No significant influence of 6-MP on their development,
      including the occurrence of leukemia, was apparent. However, the incidences of
      some proliferative lesions in the lung, intestine and kidney were slightly higher
      in the ENU/6-MP group than the ENU group. Further studies may be needed on
      promoting effects of 6-MP, based on dose-effect relation using several 6-MP doses
      and/or other initiators.

PMID- 1394120
TI  - Inhibitory effect of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel
      synthesized retinoid, on azoxymethane-induced intestinal carcinogenesis in rats.
AB  - Modifying effects of 5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone, a novel
      synthesized retinoid (KYN-54), on intestinal carcinogenesis were examined in a
      rat model using azoxymethane (AOM). A total of ninety male F344 rats, 6 weeks
      old, were divided into 4 groups. Group 1 (20 rats) was fed a diet containing KYN
      54 at a concentration of 0.02% for 3 weeks, during which time 2 s.c. injections
      of azoxymethane (15 mg/kg) were applied and then kept on a basal diet until the
      end of the experiment (1 year). Group 2 (30 rats) was given azoxymethane as in
      group 1 and fed the basal diet throughout, without synthetic retinoid exposure.
      Group 3 (20 rats) was administered KYN-54 at the commencement of the experiment,
      but not given the carcinogen. Group 4 (20 rats) received a basal diet alone
      throughout the experiment and served as a control. Intestinal tumors were seen in
      groups 1 and 2, their incidence and average number in group 1 (74%, 1.07 +/-
      0.87) being significantly less than in group 2 (39%, 0.56 +/- 0.78) (P < 0.02 and
      P < 0.05, respectively). These results suggest that the synthetic retinoid might
      be a promising chemopreventive agent for intestinal neoplasia.

PMID- 1394121
TI  - Microscopic localization of sterically stabilized liposomes in colon carcinoma
      bearing mice.
AB  - Using light and electron microscopy, we investigated the in vivo distribution of
      liposomes sterically stabilized by specific lipids which prolong their
      circulation in blood. Tissue distribution of sterically stabilized liposomes
      composed of distearoyl phosphatidylcholine:cholesterol:monosialoganglioside GM1
      (10:5:1)-encapsulated 67Ga-Desferal indicates that more than 30% of liposomes
      still remain in the blood at 24 h after tail vein injection. Moreover, such
      liposomes accumulated in tumors (C-26 colon carcinoma cells implanted s.c.),
      reaching almost the same level of uptake as liver (approximately 20% injected
      dose/g tissue). The microscopic localization of liposomes labeled with
      encapsulated colloidal gold or rhodamine-labeled dextran coincided well with the
      tissue distribution. To evaluate circulation parameters, two sizes of gold
      containing egg phosphatidylcholine:cholesterol:distearoyl
      phosphatidylethanolamine (derivatized at its amino position with a 1900 molecular
      weight segment of polyethylene glycol) (10:5:0.8) liposomes were injected. The
      plasma was examined by electron microscopy of negative-stained preparations at
      0.5, 4, and 24 h after liposome injection. It was found that the ratio of small
      (less than 100 nm diameter) to large (greater than 100 nm) liposomes increased
      with time, indicating a much faster clearance of the larger liposomes. To detect
      the localization of liposomes in various tissues, appropriate samples were fixed
      24 h after the injection of gold-containing liposomes (between 80 and 100 nm in
      diameter) composed of egg phosphatidylcholine:cholesterol:monosialoganglioside
      GM1 (10:5:1) or egg phosphatidylcholine:cholesterol:derivatized distearoyl
      phosphatidylethanolamine. The tissues examined for this study included normal
      liver, bone marrow, and implanted neoplasms. Silver-enhanced colloidal gold was
      found predominantly within Kupffer cells in the normal liver and within
      macrophages in the bone marrow. Rarely were any silver-enhanced gold particles
      detected in hepatocytes. In all preparations, electron microscopy revealed the
      presence of gold in endosomes and lysosomes of fixed sinusoidal lining
      macrophages in the liver and bone marrow. Peripheral to the implanted tumors,
      silver enhancement revealed gold in small blood vessels and focally beyond the
      vessel boundaries in extracellular spaces around tumor cells. Gold particles were
      not observed within the tumor cell cytoplasm. At the tumor border, nonenhanced
      gold was occasionally seen by electron microscopy in cells of the mononuclear
      phagocyte system. We obtained the same localization pattern as with silver
      enhancement by using an alternative aqueous content marker, rhodamine B
      isothiocyanate-dextran. We conclude that liposomes of specific composition, which
      have the ability to remain in circulation with a half-life of 12-24 h, are also
      able to transverse the endothelium of small blood vessels, including those in
      tumors, and extravasate into extracellular spaces.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1394122
TI  - Molecular and genetic analysis of liver oncogenesis in transforming growth factor
      alpha transgenic mice.
AB  - Overexpression of a transforming growth factor alpha (TGF-alpha) transgene
      induced the development of liver tumors in 69 of 93 (74%) adult male mice. To
      identify factors associated with oncogenesis, liver tumors from transgenic
      animals were characterized at the molecular level. TGF-alpha RNA transcripts were
      elevated in 17 of 25 (68%) liver tumors, relative to adjacent nontumorous tissue.
      Expression of the endogenous c-myc and insulin-like growth factor II genes was
      enhanced in 7 of 19 (37%) and 12 of 16 (75%) tumors, respectively. In contrast,
      epidermal growth factor receptor RNA levels were unchanged or reduced in all
      liver tumors, and mutations were not detected in either the Ha-ras or Ki-ras
      genes. The occurrence of liver tumors in castrated TGF-alpha transgenic mice was
      reduced about 7-fold, while in ovariectomized transgenic animals the incidence
      was increased about 6-fold. The progeny of a cross between CD1-derived TGF-alpha
      transgenic (MT42) and C57BL/6 mice exhibited no reduction in tumor burden (83%);
      however, the incidence of tumor formation in MT42 x FVB/N offspring was
      substantially lower (19%). We conclude that in these transgenic mice TGF-alpha
      promotes tumor formation and appears to play a major role in tumor progression.
      Moreover, other factors that may collaborate in TGF-alpha-induced
      hepatocarcinogenesis include c-myc, insulin-like growth factor II, sex hormones,
      and the genetic background upon which the transgene operates.

PMID- 1394123
TI  - Cathepsin D as a prognostic indicator for node-negative breast cancer patients
      using both immunoassays and enzymatic assays.
AB  - This is a retrospective study on 162 node-negative patients, with both
      biochemical and clinical factors being measured for determination of prognostic
      markers. Steroid receptors were measured on all tumors, while tumor size,
      histological grade, ploidy status, and cell cycle kinetics indicators could not
      be found or measured on 25 or less of the patient group. The primary focus of
      this study was the measurement of cathepsin D, analyzed by two different
      procedures, and 161 of the 162 patients had at least one value. The antigenic
      assay was performed using the US-CIS kit, and it was sensitive and reproducible.
      A biochemical assay using the enzymatic activity of cathepsin D was developed,
      and it gave proportional values, compared to the antigenic assay values (r2 =
      0.79). Our results indicated that the mean antigenic levels were 20% higher than
      the biochemical assay levels (P = 0.001). High levels of cathepsin D by the
      antigenic assay predicted poor relapse-free (P = 0.0001) and overall (P = 0.0004)
      survival. High levels of cathepsin D by the biochemical assay also predicted poor
      relapse-free (P = 0.031) and overall (P = 0.0013) survival. The cathepsin D
      values were still useful as predictors of outcome after multivariate analysis.
      Several other factors, such as grade and S phase, were useful as additional
      prognostic indicators. In conclusion, cathepsin D is the most useful marker in
      node-negative patients, and the analysis can be performed by both a biochemical
      and an antigenic assay.

PMID- 1394124
TI  - Quantitative imaging of a radiotherapeutic drug, Na2B12H11SH, at subcellular
      resolution in tissue cultures using ion microscopy.
AB  - The effectiveness of boron neutron capture therapy is predicted to be dependent
      not only on the amount of boron taken up by the target cells but also on the
      intracellular distribution of boron. Using the isotopic imaging technique ion
      microscopy, we have quantitatively determined uptake and intracellular
      distribution of Na2B12H11SH, a promising boron drug for boron neutron capture
      therapy, in four human cell lines: U87 glioblastoma cells, HeLa epithelioid
      carcinoma cells, GM 2408b mutant skin fibroblasts, and GM 3348b skin fibroblasts.
      The boron uptake of all four cell lines, after exposure to 100-500 micrograms/ml
      Na2B12H11SH, increased as the dosages were increased but showed a tendency toward
      saturation. Boron was more concentrated in the cytoplasm than in the nucleus but
      was not strongly localized within cells. There were no significant differences in
      boron uptake among the four cell lines. A retention experiment identified at
      least two different intracellular boron pools, and cells lost greater than 60% of
      intracellular boron within 1 h upon changing to Na2B12H11SH-free medium,
      indicating a largely low affinity binding.

PMID- 1394125
TI  - Expression and functional role of the p75 interleukin 2 receptor chain on
      leukemic hairy cells.
AB  - Hairy cell leukemia is a chronic lymphoproliferative disorder characterized by
      the expansion of neoplastic B-cells expressing the p55 chain of the interleukin 2
      receptor (IL-2R) system that is recognized by anti-CD25 monoclonal antibodies
      (mAb) and binds interleukin 2 (IL-2) with low affinity. In the present study we
      investigated leukemic hairy cells (HC) for the presence of the p75 IL-2R chain
      which binds IL-2 with intermediate affinity and plays a crucial role in
      transducing the message to the cell. For this purpose, we tested highly enriched
      leukemic HC from six hairy cell leukemia patients for the presence of IL-2R
      transcripts and for the expression of the p55 and p75 IL-2R chains on their
      surface membrane by flow cytometry and immunoprecipitation analyses. The
      functional role of IL-2 in the regulation of HC proliferation was also
      investigated. Our results indicate that freshly isolated HC express detectable
      messages for both the p75 IL-2R and the p55 IL-2R. Flow cytometry analysis
      demonstrated detectable levels of p75 IL-2R on the HC from all patients tested. A
      mixture of two specific mAb was able to immunoprecipitate detectable amounts of
      p75 IL-2R from leukemic HC. When leukemic HC were cultured in the presence of
      several concentrations of IL-2 a low proliferative response was observed.
      Moreover, the IL-2-driven proliferation of HC was markedly inhibited by anti-p75
      IL-2R mAb and to a lesser extent by anti-p55 IL-2R mAb. These findings provide
      direct evidence of the expression of different IL-2 receptors on leukemic HC and
      suggest that these molecules might play a role in leukemic cell growth.

PMID- 1394126
TI  - Amplification of genes within the chromosome 11q13 region is indicative of poor
      prognosis in patients with operable breast cancer.
AB  - Amplification of the chromosome 11q13 region, which harbors the BCL1 region and
      the PRAD1, EMS1, HSTF1, and INT2 genes, was found in 36 (16%) of a series of 226
      breast carcinomas. In the 153 patients with stage I-IIIa disease who had received
      no therapy prior to surgery and who were treated with curative intent, 11q13
      amplification was associated with the presence of lymph node metastases (P less
      than 0.002). The presence of an 11q13 amplification was associated with a
      significantly shorter relapse-free survival (P less than 0.002) and a higher
      breast cancer-specific mortality (P less than 0.003). Stepwise multivariate
      analysis showed that, in addition to lymph node status, 11q13 amplification was
      the best predictor for short survival. Stratified log-rank analysis indicated
      that, within the group of lymph node-positive breast cancer patients, 11q13
      amplification identifies a subgroup at high risk.

PMID- 1394127
TI  - Tumor progression in vivo: increased soybean agglutinin lectin binding, N
      acetylgalactosamine-specific lectin expression, and liver metastasis potential.
AB  - Tumors which grew out from threshold s.c. inocula of L5178Y-F9 and SL2-5 murine T
      cell lymphomas in syngeneic DBA/2 mice exhibited a unified natural defense
      resistant phenotype including an increased tumorigenicity and correlating
      reductions in susceptibility to natural antibodies, natural killer cells, and
      activated macrophages in vitro. The metastatic potential and cell surface
      saccharide expression of these cells were determined to assess the impact of
      growth from a small tumor focus in vivo on subsequent metastatic ability and to
      determine whether there was any association with changes in cell surface
      carbohydrates, which have been implicated now for many years in tumor
      development. A significantly increased liver-colonizing ability was observed
      following i.v. injection. The most consistent change in cell surface saccharide
      expression detected in studies using five lectins was an increase in N-acetyl-D
      galactosamine (D-GalNAc)-specific soybean agglutinin (SBA) binding. The log of
      experimental liver metastasis, SBA binding, and the percentage of hepatocyte
      rosetting of the parental and in vivo-selected cells exhibited significant direct
      correlations. While inhibition of rosetting with in vivo-selected lines by D
      GalNAc and galactose was consistent with the involvement of the D-galactose/D
      GalNAc-specific hepatocyte receptor, preincubation of the tumor cells but not
      hepatocytes with D-GalNAc inhibited hepatocyte rosetting and D-GalNAc inhibited
      homotypic tumor cell binding. These data suggest a role for a saccharide
      specific, lectin-like receptor on tumor cells in both interactions and therefore
      in the increased experimental liver metastasis. Furthermore, the increased
      expression of D-GalNAc-inhibitable SBA binding sites on the in vivo-selected
      variants should increase the homotypic binding by the D-GalNAc-specific lectin
      like receptors on the tumor cells providing a rationale for the direct
      relationship observed between increased SBA binding and i.v. metastatic
      potential.

PMID- 1394129
TI  - Antisense-mediated specific inhibition of P120 protein expression prevents G1- to
      S-phase transition.
AB  - A pentadecadeoxyribonucleotide (5'-AAAGCCCCCCACCAC), complementary to a splice
      junction site of mRNA for human proliferation-associated nucleolar protein P120,
      inhibited expression of the P120 gene and the mitogen-induced proliferation of
      human lymphocytes. The inhibition of P120 gene expression and proliferation was
      concentration dependent and reached 90% at 200 microM, as measured by
      [3H]thymidine uptake and by densitometric scanning of Northern (mRNA) and Western
      (protein) blots of P120. Inhibition was not observed in cells treated with the
      correspondent nonsense oligomer. P120 antisense oligomer treatment prevented S
      phase entry of mitogen-stimulated lymphocytes, as determined by flow cytometric
      analysis, but did not block G0-G1 transition assessed by morphological blast
      transformation and induction of [3H]uridine incorporation. Results of this study
      suggest that P120 expression may be required for the upregulation of nucleolar
      function necessary for cell proliferation.

PMID- 1394128
TI  - Homogeneously staining region in anthracycline-resistant HL-60/AR cells not
      associated with MDR1 amplification.
AB  - Anthracycline-resistant HL-60/AR cells and their drug-sensitive HL-60/S
      counterparts were characterized by karyotypic analysis and examined for the
      overexpression of DNA and mRNA sequences coding for P-glycoprotein (Pgp). The HL
      60/S cells were karyotypically stable over a 5-year period of study (1986-1991),
      except for an additional small Giemsa-positive band noted at 7q22 in cultures
      harvested in 1987, but not in 1986. This change did not affect drug sensitivity.
      The drug-resistant HL-60/AR cells examined in 1986, 1987, and 1991 demonstrated a
      very stable karyotype. The most striking feature was a large homogeneously
      staining region in the long arm of chromosome 7 (7q11.2), and translocation of
      the remainder of the long arm to another centromere. Other changes in the HL
      60/AR cells included inversion in 9q, partial deletion of the short arm of
      chromosome 10p, addition of material to the p arm of der(16), loss of chromosome
      22, and the appearance of a new marker chromosome. Both HL-60/S and the HL-60/AR
      cells were found not to amplify DNA or mRNA sequences coding for the Pgp. Thus,
      although the HL-60/AR cells possess the classical multidrug resistance phenotype
      and demonstrate a homogeneously staining region near the region of the MDR1 gene,
      their resistance is due to mechanisms other than those coded for by MDR1.

PMID- 1394130
TI  - Epigenetic silencing of the DNA repair enzyme O6-methylguanine-DNA
      methyltransferase in Mex- human cells.
AB  - Regulation of the expression of the DNA repair enzyme O6-methylguanine-DNA
      methyltransferase (MGMT) has been investigated in a number of human
      lymphoblastoid cell lines. In a number of Mex- cell lines that do not express
      methyltransferase activity, CpG sequences in the mgmt gene were hypomethylated
      with respect to methyltransferase-expressing Mex+ lines. In the cell line
      GM1953(S), in which the mgmt gene is coregulated with the thymidine kinase and
      galactokinase genes, reexpression of all three activities was experimentally
      induced. In this case, the mgmt gene in the nonexpressing cells was found to be
      hypermethylated and underwent a demethylation at CpG sequences that was
      coincident with the reappearance of the mgmt mRNA and the three enzyme
      activities. The simultaneous silencing of three activities in these cells was
      correlated with an increase in DNA 5-methylcytosine that was widespread
      throughout the genome. The data indicate that MGMT expression can be controlled
      epigenetically in human lymphoid cell lines, although the relationship between
      cytosine methylation and MGMT expression is complex. Furthermore, the rapid
      alterations in methylation in GM1953(S) cells indicate the existence of signals
      that can induce widespread and abrupt alterations in cytosine methylation in
      human cells in culture.

PMID- 1394131
TI  - Enhanced sensitivity of human colon tumor cell lines in vitro in response to
      thermochemoimmunotherapy.
AB  - We have investigated the cytotoxic responses in vitro of three human colon tumor
      cell lines with epithelial-like morphology, DLD-1, HCT-15, and HT-29, to
      thermochemoimmunotherapy with hyperthermia (42 degrees C for 2 h), carboplatin,
      and recombinant human tumor necrosis factor (TNF). Dose ranges of carboplatin and
      recombinant human TNF were administered essentially simultaneously and were
      followed 1 h later by hyperthermia. A two-tiered approach was used to evaluate
      cytotoxicity. In the first tier, a 5-day microcytotoxicity assay using vital dye
      staining was done; the effect on surviving fraction of simultaneously varying
      carboplatin and recombinant human TNF doses was evaluated by response surface
      methodology. From this analysis doses were selected for use in the second-tier
      clonogenic survival assays. A similar treatment protocol was used in clonogenic
      assays. Both assays revealed significant interline treatment response
      heterogeneity. Only the HCT-15 cells were sensitive to TNF alone; carboplatin
      activity against all three tumor cell lines was enhanced by TNF. Hyperthermia had
      minimal effect as a sole agent but enhanced the effects of carboplatin and TNF in
      DLD-1 and HCT-15 cells. Triple modality treatment resulted in 3-4-log decreased
      survival and could reduce cytotoxic resistance expressed against single- or dual
      modality treatments by some of these cells.

PMID- 1394133
TI  - p53 mutations in breast cancer.
AB  - We have identified and analyzed 41 mutations in p53 in sporadic breast tumors
      from 136 unselected breast cancer patients and estimate that approximately 40% of
      such tumors contain p53 mutations. The frequency of G-T transversions and the
      incidence of guanosine mutations in the nontranscribed strand of the p53 gene
      were found to be higher than expected, and we suggest, therefore, that exogenous
      carcinogens have an etiological role in sporadic breast cancers. Mutations were
      recorded in 44 codons of the p53 gene, with no obvious mutational hot-spots,
      although mutations at codons 175, 194, 273, and 280 accounted for 25% of the
      changes. One germ-line mutation was found in 136 patients and so we conclude that
      constitutional mutation of p53 may be an uncommon etiological factor in breast
      cancer.

PMID- 1394132
TI  - Selenoperoxidase-mediated cytoprotection against merocyanine 540-sensitized
      photoperoxidation and photokilling of leukemia cells.
AB  - Photodynamic therapy with the lipophilic sensitizing dye merocyanine 540 (MC540)
      is a promising new approach for extracorporeal purging of neoplastic cells from
      autologous remission bone marrow grafts. Resistance-conferring cellular defenses
      against the cytotoxic effects of MC540/photodynamic therapy have not been well
      characterized. This study focuses on the cytoprotective effects of the
      glutathione-dependent selenoperoxidases GPX and PHGPX, which can detoxify a wide
      variety of hydroperoxides, including lipid-derived species (LOOHs). Murine
      leukemia L1210 cells were grown in 1% serum media without [L.Se(-)] and with
      [L.Se(+)] selenium supplementation. L.Se(-) cells expressed 10- to 20-fold lower
      GPX and PHGPX activities than L.Se(+) controls and were markedly more sensitive
      to MC540-mediated photoperoxidation (LOOH formation) and clonally assessed
      photokilling. Susceptibility of L.Se(-) cells to photoperoxidation and
      photokilling could be fully reversed to L.Se(+) levels by replenishing Se, and
      partially reversed by treating with Ebselen, a selenoperoxidase mimetic. Altered
      lipid composition, greater uptake of MC540, and defective catabolism of H2O2 were
      all ruled out as possible factors in the elevated photosensitivity of L.Se(-)
      cells. Human leukemia K562 cells (capable of expressing PHGPX but not GPX)
      exhibited 5- to 10-fold lower PHGPX activity under Se-deficient relative to Se
      sufficient conditions. Although MC540 uptake (nmol/mg lipid) by K562 and L1210
      cells was essentially the same, the former were more resistant to
      photoinactivation. However, like murine counterparts, Se-deficient cells were
      more susceptible to photoperoxidation and photokilling than Se-sufficient
      controls. These results clearly demonstrate that GPX and/or PHGPX in L1210 cells
      and PHGPX in K562 cells play an important cytoprotective role during
      photooxidative stress. Whether membrane damage due to lipid photoperoxidation is
      causally related to cell death is not certain; however, the parallel effects of
      Se deficiency on LOOH formation and cell killing are at least consistent with
      this possibility.

PMID- 1394134
TI  - Phosphorous metabolite and cell cycle kinetic response of two human squamous cell
      carcinomas to radiation.
AB  - Phosphorous metabolism and cell cycle phase kinetics in response to radiation of
      two perfused human squamous cell carcinoma cell lines, SQ20B (radioresistant) and
      SQ38 (relatively radiosensitive), embedded in both basement membrane (Matrigel)
      and agarose gel threads were studied. The findings for these human cancer cells
      in response to 2- and 50-Gy irradiation are as follows. (a) Well perfused pure
      cancer cells (both SQ20B and SQ38) in both proliferative (cells embedded in
      Matrigel) and static (cells embedded in agarose threads) states did not show
      significant alteration in either phosphorous bioenergetics or membrane
      metabolites at 24 and 48 h after irradiation, although a large fraction of the
      population was clonogenically impaired. Previously reported, sensitively
      detected, metabolite alterations in response to radiation in rodent and human
      tumors in situ were not seen in these homogeneous cancer cell populations. (b)
      The radiosensitive squamous cell carcinoma cell lines SQ38 exhibited G1 block
      (from 54.38 +/- 1.40% in control to 73.93 +/- 1.01% after irradiation; mean +/
      SD) in response to low-dose 2-Gy irradiation and G2 block (from 12.98 +/- 2.15%
      in control to 25.6 +/- 3.15% after irradiation) in response to high-dose 50-Gy
      irradiation, while the radioresistant cell line SQ20B showed only conventional G2
      block in response to both doses. The differential cell cycle phase response may
      indicate the difference in radioresistance. (c) The membrane metabolites
      (including phosphomonoesters and phosphodiesters) and phosphocreatine gradually
      increased from the early passages to late passages, suggesting that cell
      proliferation rates were increasing as the cells adapted to tissue culture. The
      results suggest that the radiation-induced metabolite changes observed in solid
      tumors in situ may not be a direct response to interim changes within the cancer
      cells but, rather, a consequence of radiation damage either to the vasculature or
      to other host-mediated factors.

PMID- 1394136
TI  - Putrescine-dependent invasive capacity of rat ascites hepatoma cells.
AB  - The effects of inhibitors of polyamine synthesis on the invasive capacity of rat
      ascites hepatoma (LC-AH) cells were examined by in vitro assay of penetration of
      the LC-AH cells through a monolayer of calf pulmonary arterial endothelial (CPAE)
      cells. Pretreatment of LC-AH cells with alpha-difluoromethylornithine (DFMO), an
      inhibitor of ornithine decarboxylase, before seeding them onto a CPAE cell
      monolayer and culturing them for 24 h in the absence of DFMO decreased the number
      of penetrating tumor cells time and dose dependently (about 35% of the maximal
      inhibition) without affecting their viability or proliferative activity. DFMO
      treatment caused a marked decrease in the intracellular level of putrescine but
      not of spermidine or spermine. The DFMO-induced decreases in invasive capacity
      and putrescine level were almost completely reversed by the addition of
      putrescine to the medium during pretreatment with DFMO or invasion assay but were
      not affected by exogenous spermidine or spermine. No change in the invasive
      capacity was observed when the CPAE cells were treated with DFMO and the LC-AH
      cells with methylglyoxal-bis(guanylhydrazone), an inhibitor of S
      adenosylmethionine decarboxylase, which depressed the spermidine and spermine
      levels but increased the putrescine level in the LC-AH cells. These results
      suggest that intracellular putrescine modulates the in vitro invasive capacity of
      LC-AH cells.

PMID- 1394135
TI  - Highly sensitive, specific detection of O6-methylguanine, O4-methylthymine, and
      O4-ethylthymine by the combination of high-performance liquid chromatography
      prefractionation, 32P postlabeling, and immunoprecipitation.
AB  - A highly sensitive and specific method for the detection of O6-methylguanine (O6
      meG), O4-methylthymine (O4-meT), and O4-ethylthymine (O4-etT) has been
      established by combining prefractionation by high-performance liquid
      chromatography (HPLC), 32P postlabeling, and immunoprecipitation by monoclonal
      antibodies (PREPI method). DNA was enzymatically hydrolyzed to 2'-deoxynucleoside
      3'-monophosphates (3'-dNps). Each alkyl 3'dNp was separated by reverse-phase
      HPLC, radiolabeled at the 5' position with [gamma-32P]ATP and polynucleotide
      kinase. After removing 3'-phosphate for better recognition by the antibodies, the
      resulting alkyl nucleotides were further fractionated by HPLC and finally
      precipitated specifically with respective antibodies. The detection limits were 1
      fmol for all the alkyl nucleotides analyzed, so that one adduct in 10(8) of its
      normal counterpart nucleotide can be determined using approximately 100
      micrograms (O4-meT and O4-etT) or approximately 150 micrograms (O6-meG) of DNA,
      i.e., 3-5 x 10(7) cells corresponding to approximately 10 ml of peripheral blood
      or a few hundred milligrams of tissue. By the use of the PREPI method, three
      leukocyte and three liver DNA samples from Japanese living in the Tokyo area were
      analyzed with respect to O-alkyl adduct content. O6-meG was detected in all three
      of the leukocyte samples (O6-meG:G molar ratio, 1.1 x, 0.8 x, and 1.6 x 10(-8) as
      molar ratios to guanine). Neither O4-meT nor O4-etT was detected (detection
      limit, O4-alkylT:thymine molar ratio less than 0.5 x 10(-8)). Among the liver
      samples analyzed, two cases showed positive O6-meG values (4.2 x and 1.1 x 10(-7)
      O6-meG:guanine molar ratios). Contrary to the leukocyte DNA, O4-meT (3.9 x, 4.3
      x, and 7.5 x 10(-8) as O4-meT:thymine) and O4-etT (1.9 x, 4.9 x, and 8.7 x 10(-8)
      as O4-etT:thymine) were detected in all the liver samples. These results indicate
      the validity of the PREPI method for molecular epidemiological studies on DNA
      alkylation products.

PMID- 1394137
TI  - Involvement of the spleen in preleukemic development of a murine retrovirus
      induced promonocytic leukemia.
AB  - An acute myeloid leukemia can result from the inoculation of Moloney murine
      leukemia virus into BALB/c mice undergoing a 2,6,10,14-tetramethylpentadecane
      induced chronic inflammatory response in the peritoneal cavity. This leukemia is
      ultimately observed in the peritoneal cavity as an ascites with cells
      infiltrating the granulomatous tissue. It has been proposed, however, that
      hematopoietic organs such as the spleen and bone marrow are involved in
      preleukemic development of Moloney murine leukemia. Therefore, to determine if
      the spleen plays a role in this development, mice were splenectomized at various
      times relative to virus inoculation. When splenectomies were performed 3 days
      before and 2, 4, 6, and 8 weeks after virus inoculation there was, in all cases,
      a decreased death rate compared to sham-splenectomized controls. The greatest
      difference in death rate due to promonocytic leukemia was observed when mice were
      splenectomized at 4 weeks after virus inoculation. The decrease in disease
      incidence observed as a result of splenectomy was not caused by decreased virus
      spread in hematopoietic organs or an alteration in the profile of the cellular
      infiltrate in the granuloma. It was found, however, that the spleens of 2,6,10,14
      tetramethylpentadecane-treated mice, relative to those of normal mice, have a
      significantly increased number of granulocyte-macrophage colony-forming cells and
      a slightly increased number of multipotential colony-forming cells. These
      observations suggest that a population of target cells for transformation,
      consisting of granulocyte-macrophage precursor cells, may reside in the spleen.
      Alternatively, partially transformed cells may reside temporarily in the spleen
      during the developmental stages of the disease process.

PMID- 1394138
TI  - Marked enhancement of rat urinary bladder carcinogenesis by heat-killed
      Escherichia coli.
AB  - Chronic urinary tract infection is an important risk factor for the development
      of carcinoma in the human urinary bladder. To test the effect of chronic
      persistent inflammation on bladder carcinogenesis, we instilled heat-killed
      Escherichia coli (1 x 10(8) cells suspended in 0.5 ml of phosphate-buffered 2.1%
      NaCl solution) twice a week into the heterotopically transplanted rat urinary
      bladders in which carcinogenesis was initiated by a single dose (0.25 mg) of N
      methyl-N-nitrosourea. When compared with the control animals, the rats treated
      with killed E. coli showed significantly enhanced bladder tumorigenesis, as
      reflected by an increase in the incidence of tumor (P = 0.05) and a 6- to 40-fold
      increase in the number of tumors per bladder (P less than 0.0001). The tumors
      were characterized by intraepithelial clusterings of neutrophils and by chronic
      inflammation and marked capillary proliferation in the tumor stroma. All of these
      features were rare in tumors in the control groups. The accelerated cell
      proliferation induced by killed E. coli treatment appears to play a significant
      role in the enhancement of tumorigenesis.

PMID- 1394139
TI  - Simian virus 40 large T antigen directed by transcriptional elements of the human
      surfactant protein C gene produces pulmonary adenocarcinomas in transgenic mice.
AB  - A model of pulmonary adenocarcinomas was produced in transgenic mice harboring a
      chimeric gene comprising the SV40 large T antigen under the control of a
      transcriptional region derived from the human surfactant protein C (SP-C) gene.
      Transgenic mice succumbed with pulmonary tumors within 4-5 months of age. By
      histology, the tumors were adenocarcinomas with lepidic, papillary, and solid
      growth patterns that were indistinguishable from adenocarcinomas occurring in
      humans. Immunocytochemistry demonstrated the lack of staining for neuroendocrine
      markers, consistent with the identification of the tumors as non-small cell
      rather than small cell carcinomas. The presence of SV40 large T mRNA in the lung
      and tumors was detected by in situ hybridization and Northern blot analysis.
      Exogenous SV40 large T mRNA and endogenous CC10 (a nonciliated respiratory
      epithelial cell marker) and SP-C (a Type II alveolar cell marker) mRNAs were
      expressed at variable levels in the lung tumors. SV40 large T mRNA and CC10 mRNA
      were detected in the majority of tumors, while SP-C mRNA was detected less
      frequently. The heterogeneity of bronchiolar and alveolar cell markers in the
      tumors from the transgenic mice supports the concept that tumorigenesis was
      initiated in distinct subsets of epithelial cells that produce characteristic
      adenocarcinomas of the lung.

PMID- 1394140
TI  - Differential inhibition of the epidermal growth factor-, platelet-derived growth
      factor-, and protein kinase C-mediated signal transduction pathways by the
      staurosporine derivative CGP 41251.
AB  - The microbial alkaloid staurosporine is a potent but nonselective inhibitor of
      protein kinases. The derivative CGP 41251 has been shown to exert a high degree
      of selectivity for inhibition of protein kinase C activity. Both compounds are
      powerful inhibitors of proliferation of both normal and transformed cells in
      vitro and exert antitumor efficacy in vivo. In this work we have studied the mode
      of action of these compounds by analyzing their effects on early events in the
      induction of proliferation by different growth stimuli. Both drugs blocked the
      phorbol ester-induced expression of the c-fos proto-oncogene. The effect of CGP
      41251 was reversible, since its removal led to a normal expression of c-fos mRNA
      in response to phorbol 12-myristate 13-acetate. Submicromolar concentrations of
      CGP 41251 and staurosporine directly inhibited both the platelet-derived growth
      factor (PDGF) receptor autophosphorylation and the c-fos mRNA expression induced
      by PDGF stimulation of intact BALB/c 3T3 cells. In contrast, ligand-induced
      epidermal growth factor receptor autokinase activity in A431 carcinoma cells and
      epidermal growth factor-dependent c-fos mRNA expression were relatively
      insensitive to inhibition by CGP 41251. Staurosporine suppressed signal
      generation by the epidermal growth factor receptor by reducing overall levels of
      the receptor. We conclude that CGP 41251 is a potent reversible inhibitor of
      protein kinase C and PDGF-mediated signal transduction. It inhibits the kinase
      activity of both protein kinase C and the PDGF receptor tyrosine kinase and the
      subsequent signaling cascade. The broad inhibition of kinases by staurosporine is
      also reflected at the cellular level and might contribute to the high toxicity of
      this compound, in comparison to CGP 41251.

PMID- 1394141
TI  - Monovalent immunotoxin containing truncated form of Pseudomonas exotoxin as
      potent antitumor agent.
AB  - Recombinant truncated forms of Pseudomonas exotoxin A that lack the cell binding
      domain of Pseudomonas exotoxin A were coupled to an F(ab') fragment of a
      monoclonal antibody HB21 directed against the human transferrin receptor. One of
      these was NlysPE40. The other, NlysPE38QQR, has two amino groups on residues near
      the NH2-terminus and has no amino groups near the COOH-terminus. The proteins
      were linked by a stable thioether bond that connected the sulfhydryl group
      present in the hinge region of the antibody fragment to an amino group on the
      toxin. The F(ab')-PE40 immunotoxin, containing NlysPE40, exhibited potent
      cytotoxic activity on human carcinoma cell lines with a concentration of
      immunotoxin at which isotope incorporation falls by 50% when compared to
      nontreated cells (ID50) of 5.3 pM (0.5 ng/ml) on both the epidermoid carcinoma
      A431 and on the colon carcinoma Colo205. Immunotoxins made with whole antibody
      were considerably less active, with an ID50 of 15.9 pM (3.1 ng/ml) on these cell
      lines. F(ab')-PE38QQR, the immunotoxin containing NlysPE38QQR, was found to be
      the most active agent with an ID50 of 1.05 pM (0.1 ng/ml) on A431 cells. The
      greater cytotoxicity of immunotoxins containing fragmented antibody was probably
      due to the higher binding affinity of F(ab') conjugates in comparison to whole
      antibody conjugates to the transferrin receptor. The increase in cytotoxic
      activity of the immunotoxin made with NlysPE38QQR than that with NlysPE40 may
      reflect selective coupling of the toxin through NH2-terminal amino groups. The
      monovalent and divalent immunotoxins had dose-dependent antitumor effects on
      human epidermoid carcinoma xenografts in nude mice. A431 tumors completely
      regressed in all animals at a total dose of 105 pmol (10 micrograms) of F(ab')
      PE38QQR and of 154 pmol (30 micrograms) of IgG-PE38QQR. Furthermore, the F(ab')
      immunotoxin was less toxic to mice than the conjugate containing IgG (840 pmol or
      80 micrograms of total dose causing measurable adverse effects versus 208 pmol or
      40 micrograms, respectively). Thus, a truncated Pseudomonas exotoxin A molecule
      coupled to the F(ab') fragment of an antibody is more active and less toxic in
      mice than an immunotoxin made with a whole antibody. Therefore, the therapeutic
      index for the monovalent immunotoxin is about four times better than that for the
      divalent immunotoxin.

PMID- 1394142
TI  - Effects of tamoxifen adjuvant therapy and a low-fat diet on serum binding
      proteins and estradiol bioavailability in postmenopausal breast cancer patients.
AB  - Serum was collected at intervals from postmenopausal breast cancer patients to
      determine the effects of tamoxifen adjuvant therapy and a low-fat dietary
      intervention, alone and in combination, on sex hormone-binding globulin (SHBG)
      concentrations and circulating estradiol bioavailability. Serum corticosteroid
      binding globulin and follicle-stimulating hormone were also assayed as indicators
      of patient compliance to tamoxifen therapy. The immunoreactive SHBG concentration
      was higher (P less than 0.001) in 22 patients who had been treated with tamoxifen
      for 6-36 weeks when first sampled, compared with 27 who were not receiving
      tamoxifen therapy. Tamoxifen also produced a reduction in the percentage non
      protein-bound estradiol (P less than 0.001) and percentage albumin-bound
      estradiol (P less than 0.01), the two biologically available fractions, and a
      corresponding increase in the percentage SHBG-bound estradiol (P less than 0.01).
      A longitudinal study of 7 patients showed significant reductions in the
      percentage of albumin-bound estradiol and an increased percentage of SHBG-bound
      estradiol, after 3-6 months of tamoxifen; after 12-18 months there was also a
      significant decrease in the non-protein-bound estradiol fraction. We conclude
      that in postmenopausal breast cancer patients the redistribution of circulating
      estradiol, with reduced bioavailability, provides an additional mechanism to
      those demonstrated previously for the therapeutic activity of tamoxifen. Another
      12 patients receiving tamoxifen and 8 who were not were followed for 6-12 months
      on a low-fat diet (fat comprised 20% of the total calories). The dietary
      intervention had no effect on the serum SHBG concentration or the estradiol
      distribution. Although tamoxifen increased the serum corticosteroid-binding
      globulin and partially suppressed the follicle-stimulating hormone
      concentrations, the responses obtained were less consistent compared with those
      of the SHBG levels.

PMID- 1394143
TI  - Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical
      identification of aluminum.
AB  - An increase in fibrosarcomas in a biopsy population of cats in the Pennsylvania
      area appears to be related to the increased vaccination of cats following
      enactment of a mandatory rabies vaccination law. The majority of fibrosarcomas
      arose in sites routinely used by veterinarians for vaccination, and 42 of 198
      tumors were surrounded by lymphocytes and macrophages containing foreign material
      identical to that previously described in postvaccinal inflammatory injection
      site reactions. Some of the vaccines used have aluminum-based adjuvants, and
      macrophages surrounding three tumors contained aluminum oxide identified by
      electron probe microanalysis and imaged by energy-filtered electron microscopy.
      Persistence of inflammatory and immunological reactions associated with aluminum
      may predispose the cat to a derangement of its fibrous connective tissue repair
      response, leading to neoplasia.

PMID- 1394144
TI  - A synthetic antagonist to laminin inhibits the formation of osteolytic metastases
      by human melanoma cells in nude mice.
AB  - The mechanisms by which tumor cells metastasize to bone are not well understood.
      We have investigated the role of the basement membrane glycoprotein, laminin, in
      bone metastasis, since antagonists to laminin have been shown to inhibit the
      formation of lung metastases. We studied the formation of osteolytic metastases
      caused by a human tumor which is known to cause osteolysis and hypercalcemia in
      nude mice. We found that tumor-bearing nude mice developed hypercalcemia,
      cachexia, and characteristic osteolytic lesions throughout the skeleton after
      injection of this human melanoma cell line (A375) into the left ventricle. When
      we gave injections to nude mice with A375 cells which had been exposed to
      C(YIGSR)3-NH2, a laminin-derived synthetic peptide containing three linear
      sequences of YIGSR with an amino-terminal cysteine which competes with laminin
      for its receptor, we found a decrease in the formation of detectable osteolytic
      bone metastases. The tumor cells were incubated with the antagonist and then
      inoculated into nude mice which were administered the antagonist i.p.
      Hypercalcemia and cachexia were also decreased in tumor-bearing mice treated with
      the laminin antagonist. In contrast, laminin itself increased the number of
      osteolytic bone metastases, as has been shown for other tumor cells. These data
      suggest that laminin plays a role in the formation of osteolytic bone metastases
      in this model and that laminin antagonists may be useful in the prevention of
      bone metastases in some human tumors.

PMID- 1394145
TI  - Activation of omental milky spots and milky spot macrophages by intraperitoneal
      administration of a streptococcal preparation, OK-432.
AB  - Omental milky spots are omentum-associated lymphoid tissues that cede peritoneal
      macrophages and participate in the immunity of the peritoneal cavity. We studied
      the changing surface features of milky spots and milky spot macrophages of Wistar
      rats, following the i.p. administration of OK-432, a killed streptococcal
      preparation (1 Klinische Einheit (unit) in 5 ml of phosphate-buffered saline) by
      the use of scanning electron microscopy. OK-432-activated macrophages
      demonstrated marked surface membrane activity and migrated through the stomata of
      the milky spot into the peritoneal cavity. The characteristic features of
      activated milky spots and milky spot macrophages were noted as early as 3 h
      following the administration of OK-432, and continued to be observed until 7 days
      after the injection. By 14 days after the injection, the structural integrity of
      the milky spot was partially lost. The activation of milky spots and milky spot
      macrophages by OK-432 provides a convenient in vivo system for the monitoring and
      study of i.p. cellular events.

PMID- 1394146
TI  - bcl-2 gene transfer increases relative resistance of S49.1 and WEHI7.2 lymphoid
      cells to cell death and DNA fragmentation induced by glucocorticoids and multiple
      chemotherapeutic drugs.
AB  - The S49.1 and WEHI7.2 murine lymphoid cell lines have been used extensively as
      models for investigations of programmed cell death ("apoptosis") induced by
      glucocorticoids such as dexamethasone. Infection of these thymus-derived T-cell
      lines with a recombinant retrovirus encoding the human M(r) 26,000 Bcl-2
      oncoprotein resulted in marked resistance to DEX-mediated cell death and DNA
      degradation into oligonucleosomal fragments, without interfering with the ability
      of dexamethasone to suppress cellular proliferation and without lowering levels
      of glucocorticoid receptors. In contrast, high levels of p26-Bcl-2 production did
      not block cell killing and DNA fragmentation induced by H2O2, suggesting that the
      Bcl-2 impairs some but not all pathways for cell death in S49.1 and WEHI7.2 cells
      that are associated with the DNA fragmentation pattern typical of apoptosis.
      S49.1 and WEHI7.2 cells infected with bcl-2 but not control retrovirus also
      exhibited increased resistance to cell killing and DNA fragmentation induced by a
      wide variety of reagents, including the calcium ionophore ionomycin, the phorbol
      ester tetradecanoylphorbol acetate, the dihydrofolate reductase inhibitor
      methotrexate, the antimetabolite 1-beta-D-arabinofuranosylcytosine, and the
      microtubule inhibitor vincristine. These findings provide evidence that p26-Bcl-2
      interferes with a pathway for cell death that is activated by multiple drugs used
      for the treatment of cancer.

PMID- 1394147
TI  - In vivo and in vitro characteristics of interleukin 6-transfected B16 melanoma
      cells.
AB  - Interleukin 6 (IL-6) is a multifunctional cytokine important in the inflammatory
      response. Its potential role as an antitumor agent has been suggested by its
      demonstrated activity in a variety of tumor models. The mechanism of antitumor
      activity has been proposed to be its enhancement of cytotoxic T-cell function. In
      the current work we demonstrate clear antitumor activity for this cytokine in a
      nonimmunogenic tumor system. B16 melanoma cells transfected with the human IL-6
      complementary DNA demonstrated slower tumor growth in vivo. Tumors that developed
      from these cells had a prominent stromal matrix, an easily recognized
      infiltration of inflammatory cells, fewer mitotic figures, and fewer blood
      vessels. These in vivo findings corresponded with a greater adhesion of the IL-6
      transfected B16 cells to stromal matrix proteins (laminin, fibronectin, and
      vitronectin) and a less prominent vascular response in an intradermal
      angiogenesis assay. Therefore, we propose that with weakly antigenic tumors, such
      as B16 melanoma, IL-6 may mediate important antitumor responses by nonspecific
      proinflammatory mechanisms.

PMID- 1394149
TI  - Non-Hodgkin's lymphoma time trends: United States and international data.
AB  - Incidence data from the Surveillance, Epidemiology, and End Results Program of
      the National Cancer Institute, earlier incidence surveys, and the International
      Agency for Research on Cancer, mortality data from the National Center for Health
      Statistics, and population data from the Census Bureau were used to assess rates
      of non-Hodgkin's lymphoma. Mortality and incidence rates have been increasing for
      many years. Larger increases among older persons suggest a role for improving
      diagnosis, particularly during the 1950s and 1960s. Urban/rural and socioeconomic
      differences have diminished over time. Since the early 1970s, incidence rates
      increased at 3-4%/year, more rapidly than for all other cancers except melanoma
      of the skin and lung cancer among women. Incidence rates increased over all ages
      except the very young, among whites and blacks, in geographic areas both in the
      United States and internationally, and both sexes. During the 1980s, the impact
      of AIDS is apparent among young and middle-aged men. Differences in non-Hodgkin's
      lymphoma rates persist between races and sexes. Increases have been more marked
      for extranodal disease, particularly those arising in the brain, and for high
      grade tumors. Explanations accounting for all the increases in rates are not
      readily available.

PMID- 1394148
TI  - An ovarian tumor marker with homology to vaccinia virus contains an IgV-like
      region and multiple transmembrane domains.
AB  - The monoclonal antibody OVTL3 has a highly restricted reactivity with ovarian
      carcinomas and defines a surface glycoprotein, OA3, which has been used for
      immunotargeting. To understand why OA3 is found on ovarian tumors we isolated a
      complementary DNA by expression cloning. The clone encodes a 323-amino acid
      protein with 5 putative membrane spanning domains, reminiscent of a membrane
      receptor or channel, but of a new type with little or no sequence similarity with
      these families of proteins. Interestingly, the OA3 sequence is highly related to
      a vaccinia virus encoded protein (VA38) and its extracellular domain is a member
      of the immunoglobulin V region superfamily.

PMID- 1394150
TI  - Changes in the descriptive epidemiology of non-Hodgkin's lymphoma in Great
      Britain?
AB  - The problems associated with a diagnosis of non-Hodgkin's lymphoma are reviewed
      in the context of an apparent rise in incidence. It is concluded that a true rise
      exists and that further work is required to fully understand the significance of
      this.

PMID- 1394151
TI  - Time trends of non-Hodgkin's lymphoma: are they real? What do they mean?
AB  - Factors that need to be considered in the analysis of time trends in disease
      incidence are age, year of diagnosis, and birth cohort. When these are included
      in a log-linear model, a nonidentifiability problem arises from the linear
      dependence among these three time factors so that only specified functions of the
      parameters can be unambiguously determined. One of these invariant functions is
      the drift or the sum of the period and cohort trend. Non-Hodgkin's lymphoma
      incidence rates from Connecticut for the period 1935-1989 were analyzed for males
      and females. In addition to an age effect, both period and cohort significantly
      improved the fit of the model. The estimated drift shows that there has been a
      10.3% increase in risk every 5 years since 1965 for females and 9.2% for males.
      It is unlikely that a trend of this magnitude can be attributed entirely to data
      artifact.

PMID- 1394152
TI  - An overview of the classification of non-Hodgkin's lymphomas: an integration of
      morphological and phenotypical concepts.
AB  - An analysis of trends in the incidence of non-Hodgkin's lymphoma requires an
      understanding of individual disease entities within this broad group. The non
      Hodgkin's lymphomas represent a diverse group of malignancies that have in common
      an origin from lymphoid cells. Nevertheless, these disorders are heterogeneous in
      their clinical behavior, morphological appearance, cellular origin, etiology, and
      pathogenesis. A modern classification of non-Hodgkin's lymphomas must include an
      integration of morphological, immunophenotypical, and molecular concepts in order
      to delineate individual diseases within this broad group. Existing classification
      schemes such as the working formulation, while they may be useful in providing a
      guide to clinical management, cannot provide this information in the absence of
      other data. This point is most readily made with the low-grade B-cell lymphomas
      which include follicular lymphomas, mantle cell lymphomas, small lymphocytic
      lymphomas, immunosecretory disorders, and lymphomas of mucosa-associated lymphoid
      tissues. Each of these malignancies has a distinct phenotype and genotype, and
      indubitably each has a different etiology. The postthymic T-cell tumors are
      equally diverse. Analysis of epidemiological data from cancer registries must
      include a recognition that our ability to recognize individual diseases from
      historical data is limited. Studies of trends in the non-Hodgkin's lymphomas
      should attempt to delineate biological markers that may be of relevance to
      pathogenesis in both historical and prospectively accrued cases.

PMID- 1394153
TI  - Changes in diagnosis of non-Hodgkin's lymphomas over time.
AB  - The question is raised as to whether changes in criteria for the diagnosis of non
      Hodgkin's lymphomas, both clinical and pathological, have changed over the past
      four decades in sufficient scale to create a spurious increase in the apparent
      incidence of this grouping of disease. In the decade of the 1970s refinement in
      histomorphological criteria for the diagnosis of Hodgkin's disease resulted in as
      many as 10-15% of cases which previously would have been diagnosed as Hodgkin's
      disease being diagnosed instead as non-Hodgkin's lymphoma. Other considerations,
      including distinction of non-Hodgkin's lymphomas from leukemias and plasma cell
      myelomas, and recent recognition of angioimmunoblastic lymphadenopathy and
      extranodal "pseudolymphomas" as variant forms of non-Hodgkin's lymphoma, appear
      to have added only marginally to the total of reported cases. It is concluded
      that the increase in reported incidence of non-Hodgkin's lymphoma cannot be
      explained on the basis of changes in diagnostic criteria.

PMID- 1394154
TI  - Pathological classification of non-Hodgkin's lymphoma for epidemiological
      studies.
AB  - Non-Hodgkin's lymphoma (NHL) consists of a heterogeneous group of disorders which
      have been difficult to study by epidemiological means in the past. However,
      recent advances in knowledge of the biology of NHL and improvements in its
      classification will greatly improve the quality of epidemiological studies in the
      future. Use of the Working Formulation and the current International
      Classification of Diseases for Oncology, along with paraffin
      immunohistochemistry, allow the delineation of NHL subgroups with possible
      etiological significance based on the biology of the disease. The collaboration
      of epidemiologists with expert pathologists in the design, performance, and
      evaluation of epidemiological studies of NHL is essential for such studies to be
      meaningful.

PMID- 1394155
TI  - Familial aggregation of hematopoietic malignancies and risk of non-Hodgkin's
      lymphoma.
AB  - Examination of risk factors that may be responsible for the increasing incidence
      of non-Hodgkin's lymphoma (NHL) over the past few decades would be incomplete
      without considering familial aggregation of hematolymphoproliferative neoplasms
      and the relative contributions of heredity and environment to the etiology of
      NHL. Reports of families with two or more NHL cases and sometimes additional
      members affected by other hematopoietic malignancies (multiple-case families) are
      summarized, as are findings from surveys and quantitative risk estimates from
      population-based studies of familial aggregation. The notable occurrence of
      various immunological abnormalities among multiple-case family members with and
      without NHL or related neoplasms is underscored, as is the diversity of types of
      other lymphoproliferative and hematopoietic malignancies among close relatives in
      these families. Preliminary evidence suggesting that multiple-case families may
      be more susceptible to certain environmental exposures is presented. An
      international registry of such families (particularly those identified in
      population-based studies) is proposed to clarify the interrelationship of
      genetic, familial, and environmental factors in the etiology of NHL.

PMID- 1394156
TI  - Immunosuppressive therapy and acquired immunological disorders.
AB  - Impairment of the immune system by drugs, such as azathioprine and cyclosporin,
      or by diseases, such as AIDS, represents the most firmly established cause of non
      Hodgkin's lymphoma (NHL). Neither drugs nor diseases, however, can explain the
      increases in the incidence of NHL in the general population, for these include
      cohorts relatively unexposed to immunosuppressive drugs or to AIDS. Furthermore,
      no immunological disorder that is associated with an increased risk of NHL is
      known to have increased in incidence. Among alternative explanations is the
      possibility of increased exposure to a lymphomagenic agent in the environment
      that acts by nonimmunological means. Pesticides and herbicides may belong to this
      category, but they will not explain the substantial increases in NHL in urban
      populations. However, the evidence of an underlying viral aetiology for the
      lymphomas in several different forms of immune impairment may be relevant to the
      increases in NHL in the general population. Paralytic poliomyelitis and mumps
      represent examples of diseases that have changed their pattern of occurrence in
      this century, consequent on changes in social conditions. It is therefore not
      impossible that changes in hygiene and in population density have altered the
      average age of exposure to a virus, thereby increasing the likelihood of a
      lymphomagenic effect.

PMID- 1394157
TI  - Lymphoma risks in populations with altered immunity--a search for mechanism.
AB  - There have been numerous studies of lymphoma incidence in patient populations
      having diseases or taking medications that result in altered immunity. While many
      of these have uncovered substantially elevated risks, little has been done to use
      these observations to gain insights into the mechanisms of lymphomagenesis.
      Speculation about mechanism has centered on either immunosuppression or
      immunostimulation. The patterns of risk among kidney transplant recipients
      (higher risks for those receiving cadaveric grafts, having multiple transplants,
      or having received transplants in the earlier years of transplantation) favor the
      immunostimulation hypothesis. Likewise, the higher lymphoma risk associated with
      indices of increasing severity of disease among patients with sicca syndrome also
      support the role of immunostimulation over that of immunosuppression. However, an
      ordering of many of the more extensively studied conditions with altered immunity
      on the basis of the relative risk of lymphoma associated with these conditions
      reveals a pattern of risk which is not completely consistent with the level of
      either immune suppression or immune stimulation. Perhaps we have reached a point
      where epidemiologists working with laboratory and clinical immunologists can
      discern a more sophisticated underlying mechanism than the crude concepts of
      immunosuppression or immunostimulation that would explain the markedly differing
      lymphoma risks seen in various groups with marked immune abnormalities. If so,
      markers of more subtle alterations in this mechanism might be profitably explored
      for their role in lymphoma in general and as a tool to define the environmental
      causes of the epidemic increases.

PMID- 1394158
TI  - Viruses other than HIV and non-Hodgkin's lymphoma.
AB  - There are several viral infections which are known to cause lymphoma among
      animals; all establish latency in lymphoid cells. The human T-lymphotropic virus
      type I is a human virus which causes lymphomas among a subset of carriers.
      However, this virus is very restricted in its distribution and as such, is
      unlikely to play a role in the increase of non-Hodgkin's lymphoma (NHL). A highly
      prevalent infection, the Epstein-Barr virus (EBV) is known to play a role in the
      etiology of NHL among persons with acquired or inherited immune suppression.
      However, whether it is involved with "spontaneous" NHL is unknown. We have found
      evidence that among a group of 104 NHL patients with blood samples taken several
      years before diagnosis, there was an alteration in the antibody profile against
      the EBV which is quite similar to that seen for immune-suppressed patients prior
      to their diagnosis. This pattern is most evident in the oldest patients. This
      suggests that there may be an age-related subclinical immune suppression leading
      to chronic activation of EBV. If a viral infection is a major factor in the
      recent increase in NHL in the world, then we should consider the role of immune
      suppressive exposures which have become widespread in recent decades.

PMID- 1394159
TI  - Pesticides and non-Hodgkin's lymphoma.
AB  - The incidence of non-Hodgkin's lymphoma (NHL) has increased over 50% in the last
      15 years. This paper reviews the possible role of pesticides in this increase.
      While small increases in risk of NHL among farmers have been observed in general
      occupational surveys, recent studies focusing on specific pesticides have
      observed much larger risks. Frequent use of phenoxyacetic acid herbicides, in
      particular, 2,4-dichlorophenoxyacetic acid, has been associated with 2- to 8-fold
      increases of NHL in studies conducted in Sweden, Kansas, Nebraska, Canada, and
      elsewhere. Canine malignant lymphoma has also been associated with dog owner use
      of 2,4-dichlorophenoxyacetic acid and commercial lawn pesticide treatments. There
      are much fewer data linking NHL to other types of pesticides, but triazine
      herbicides, organophosphate insecticides, fungicides, and fumigants have also
      been associated with increased risk of NHL. Pesticide exposures are not limited
      to agricultural populations but are widespread in the general population through
      use on lawns, golf courses, rights-of-way, and elsewhere. Since the use of
      pesticides, particularly phenoxy herbicides, has increased dramatically preceding
      and during the time period in which the incidence of NHL has increased, they
      could have contributed to the rising incidence of NHL.

PMID- 1394160
TI  - Radiation and non-Hodgkin's lymphoma.
AB  - Lymphomas are rarely, if ever, found to be in excess following exposure to
      ionizing radiation. Hodgkin's disease has never been linked to radiation, and the
      evidence for non-Hodgkin's lymphoma (NHL) is very weak. Low doses of radiation
      from diagnostic X-ray procedures or from occupational exposures do not appear to
      cause NHL. Mortality studies of atomic bomb survivors in Japan and other
      epidemiological studies with quantitative estimates of radiation dose also fail
      to find dose-response relationships. NHL may arise infrequently following high
      dose, possibly near lethal, radiation treatments. Immunosuppression associated
      with the disease being treated, such as Hodgkin's disease, may contribute to the
      development of NHL. If radiation does not cause NHL, at least not by its accepted
      mechanism of action of breaking chromosomes, creating rearrangements, gene
      deletions, and mutations, perhaps other environmental mutagens and clastogens
      should not be considered likely causes of NHL.

PMID- 1394161
TI  - Nutritional factors and the development of non-Hodgkin's lymphoma: a review of
      the evidence.
AB  - Lymphomas of the non-Hodgkin's type represent a heterogeneous group of tumors,
      probably comprised of groups of related diseases each with a distinct etiology.
      The epidemiology of non-Hodgkin's lymphoma is poorly characterized, and little is
      known about factors which increase a person's risk of developing one of these
      tumors. Available epidemiological evidence suggests the influence of a number of
      environmental factors. Although diet is potentially one of the most significant
      environmental factors that could be related to disease etiology, very little has
      been done to investigate the role of diet in the development of non-Hodgkin's
      lymphoma. In this paper, the existing epidemiological findings are reviewed, and
      the plausibility of an etiological association between dietary factors and non
      Hodgkin's lymphoma is considered in the context of relevant animal research.

PMID- 1394162
TI  - Increasing incidence of non-Hodgkin's lymphoma: occupational and environmental
      factors.
AB  - The incidence of non-Hodgkin's lymphoma (NHL) has been increasing steadily for
      the last 30 years, and attention is being focused on the possible causes of this
      increase. Possible explanations have included the exposure to viruses, radiation,
      nutrition, and pesticides, and these issues are addressed by other presentations
      in this workshop. The interest in a possible role of pesticides stems from the
      observation that farmers have an increased risk of NHL. However, farmers may also
      be exposed to oncogenic viruses carried by farm animals, and studies of abattoir
      workers and meat inspectors have found increased risks of NHL; although these
      findings are unlikely to be directly relevant to the general population, they do
      complement other suggestions that exposure to oncogenic viruses may be a factor
      in the general increase in NHL. Farmers may also be exposed to chronic antigenic
      stimulation which may increase the risk of NHL. This latter observation is
      consistent with the observation that NHL is associated with several autoimmune
      diseases which involve chronic antigenic stimulation. NHL has also been
      associated with a number of occupational exposures but these are generally rare
      and the findings are inconsistent, although a number of studies have found an
      increased risk of NHL in work involving exposure to wood, solvents, or related
      chemicals. Perhaps the strongest evidence of an association with an environmental
      exposure comes from two studies showing that use of hair dyes increases the risk
      of NHL. This exposure is relatively common in women, and hair dye use may account
      for approximately 20% of all NHL cases in women.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394163
TI  - Comments on occupational and environmental factors in the origin of non-Hodgkin's
      lymphoma.
AB  - The review of the literature regarding non-Hodgkin's lymphoma and occupational
      and environmental factors presented at this workshop suggested associations with
      viruses, solvents, and hair dyes. A population-based case-control study among men
      from Iowa and Minnesota notes similar associations. Workers engaged in metal
      working, hair care, painting, and dry cleaning experienced nonsignificant
      excesses. Risks from specific exposures showed some variation by histological
      type. Both follicular and diffuse non-Hodgkin's lymphoma were associated with
      benzene. The diffuse type was linked to solvents other than benzene and
      formaldehyde, while the follicular was excessive among workers exposed to oils
      and greases.

PMID- 1394164
TI  - Non-Hodgkin's lymphoma and occupational exposure.
AB  - A case-control study was conducted to assess the effect of occupational exposures
      on the risk of non-Hodgkin's lymphoma. Interviews were conducted with 303 persons
      with non-Hodgkin's lymphoma newly diagnosed from January 1, 1980, to May 31,
      1982, among residents of the Boston, MA, metropolitan area and 303 age and gender
      matched controls. The study found an increased risk of disease among persons
      employed in the agriculture, forestry, and fishing industry [relative risk (RR) =
      3.0]; the construction industry [RR = 2.1]; and the leather industry [RR = 2.1].
      The particular job groupings at increased risk were plant farmers and gardeners
      (RR unbounded); painters and plasterers (RR = 6.0); and carpenters, brick and
      stone masons, plumbers, and roofers (RR = 12.0). Although other exposures may
      have led to these increased risks, the findings in this study are consistent with
      an increased risk of non-Hodgkin's lymphoma for workers who may be exposed to
      chlorophenols or phenoxyacetic acids.

PMID- 1394165
TI  - Prior medication use and health history as risk factors for non-Hodgkin's
      lymphoma: preliminary results from a case-control study in Los Angeles County.
AB  - To determine whether non-Hodgkin's lymphoma (NHL) is related to prior medication
      use or health history, a population-based case-control study was conducted. A
      total of 619 male and female residents of Los Angeles County who were diagnosed
      with NHL between January 1, 1979, and June 30, 1982, were compared to
      individually age-, race-, and sex-matched neighborhood controls with regard to
      history of use of 49 different medications, 47 chronic and infectious diseases or
      other conditions, 15 types of immunizations, and 15 specific allergic reactions.
      Based on preliminary analyses, long-term regular use of aspirin and other pain
      relievers and greater than or equal to 2 mo of treatment with penicillin and
      other antibiotics were associated with significantly increased risk of NHL. Other
      drugs associated with greater risk of NHL were use of digitalis and estrogen
      replacement therapy by women, use of corticosteroids, and greater than or equal
      to 2 mo of use of tranquilizers. NHL was strongly associated with a prior history
      of cancer. Cases more frequently reported histories of kidney infections and
      anemia than did controls; a history of eczema appeared to be protective against
      NHL. Women who had been immunized against polio by injectable vaccine were at
      significantly lower risk of NHL than women who had not received this
      immunization. Among men, cholera immunization and allergy to nuts and berries
      were significantly protective. Subjects who had received a yellow fever
      immunization also had lower NHL risk. Further analyses of these data will attempt
      to establish the relative importance of these potential risk factors and to
      determine whether any are markers of early symptoms of NHL.

PMID- 1394166
TI  - Does chronic fatigue syndrome predispose to non-Hodgkin's lymphoma?
AB  - Chronic fatigue syndrome, an illness that frequently is associated with
      abnormalities of cellular immunity, has been reported anecdotally to be
      associated with an increased incidence of lymphoid hyperplasia and malignancy.
      This report describes an initial analysis of population-based cancer incidence
      data in Nevada, focusing on the patterns of non-Hodgkin's lymphoma prior to and
      subsequent to well described, documented outbreaks of chronic fatigue syndrome
      during 1984-1986. In a study of time trends in four age groups, the observed time
      trends were consistent with the national trends reported in the Surveillance,
      Epidemiology, and End Results Program. No statistically significant increase
      attributable to the chronic fatigue syndrome outbreak was identified at the state
      level. Additional studies are in progress analyzing the data at the country
      level, reviewing patterns in other malignancies, and continuing to monitor the
      cancer patterns over subsequent years.

PMID- 1394167
TI  - Pathogenetic mechanisms in B-cell non-Hodgkin's lymphomas in humans.
AB  - A very large proportion of non-Hodgkin's lymphoma in the United States are of B
      cell origin. This group of tumors includes a variety of different pathological
      and clinical types. Chromosomal rearrangements play an important role in the
      pathogenesis of many of these tumors. In B-cells these translocation processes
      appear to develop as illegitimate products of physiological V-(D)-J or heavy
      chain switch rearrangements. The biology of the well-known chromosomal
      translocations is discussed. Additional biological factors in lymphomagenesis
      (aging, immunodeficiency, role of antigenic stimulation, and genetically
      determined susceptibility) are discussed.

PMID- 1394168
TI  - Molecular basis of lymphomagenesis.
AB  - Lymphoid neoplasms, like all malignant tumors, arise as a consequence of the
      accumulation, in a single cell, of a set of genetic lesions that result in
      altered proliferation or increased clonal life span. The most frequently observed
      genetic abnormalities among the malignant non-Hodgkin's lymphomas are
      translocations, which appear to be lineage and, to a large extent, lymphoma
      specific. Recombinases that normally mediate the process of antigen receptor gene
      rearrangement appear to have an important (but not exclusive) role in the
      mediation of these translocations and of other types of gene fusion (e.g.,
      deletion of intervening DNA). Frequently, such fusions result in the increased or
      inappropriate expression of crucially important proteins, many of which are
      transcription factors that regulate the expression of other genes. These
      abnormalities, however, do not appear to be sufficient to induce lymphoma, and it
      is likely that the additional genetic lesions required differ from one tumor to
      another. The likelihood of any given clone of cells accumulating a sufficient
      number of relevant genetic lesions to give rise to a lymphoma is probably a
      function of its life span. Prolonged survival of a cell clone may be mediated by
      viral genomes (e.g., Epstein-Barr virus and human T-cell leukemia/lymphoma virus
      type 1), by the abnormal expression of cellular genes that inhibit apoptosis
      (e.g., bcl-2), or by the mutation or deletion of cellular genes that are
      necessary for apoptosis, e.g., p53. The background rate at which genetic lesions
      occur is amplified by the interaction of inherited and environmental factors, the
      latter appearing to be the major determinant of incidence rates. However,
      inherited factors that influence lymphomagenesis, including variability in the
      ability to repair DNA damage or in the fidelity of antigen receptor recombinases
      for their signal sequences, may be crucial determinants of which particular
      individuals in a given environmental setting develop lymphoma.

PMID- 1394169
TI  - Characterization of chromosome 11 translocation breakpoints at the bcl-1 and
      PRAD1 loci in centrocytic lymphoma.
AB  - The chromosome 11q13 bcl-1 locus is rearranged in the majority of centrocytic
      lymphomas, a CD5-positive B-cell non-Hodgkins lymphoma, as a result of reciprocal
      translocation with the 14q32 immunoglobulin heavy chain genes. Although several
      11q13 bcl-1 breakpoint sites have been characterized, a postulated bcl-1 oncogene
      was not identified. Recently, however, a gene encoding cyclin D1, designated
      PRAD1, was proposed as a candidate bcl-1 oncogene; accumulated evidence now
      indicates this gene is bcl-1. To further characterize 11q13 breakpoints in B-cell
      neoplasms, we analyzed 26 centrocytic lymphomas and 68 other B-cell cancers by
      Southern blot using a panel of breakpoint probes spanning 110 kilobases of the
      bcl-1 and PRAD1 loci. Nineteen centrocytic cases (73%) showed rearrangement, 15
      at bcl-1 breakpoint sites and 5 at PRAD1 sites. One case was rearranged at both
      bcl-1 and PRAD1 loci. All but the latter case showed comigration of rearranged
      bcl-1 or PRAD1 bands and immunoglobulin heavy chain joining gene bands,
      consistent with the t(11;14). bcl-1 rearrangement was present in only one of 68
      noncentrocytic B-cell neoplasms; none showed PRAD1 rearrangement. Thus, bcl-1 and
      PRAD1 rearrangement is strongly associated with centrocytic lymphoma, providing a
      useful molecular marker for classifying this subtype of lymphoma and suggesting
      an important role for PRAD1 cyclin D1 in the pathogenesis of this neoplasm.

PMID- 1394170
TI  - A measure of genomic instability and its relevance to lymphomagenesis.
AB  - A recent pilot study that we performed on 12 individuals who are involved in the
      cultivation and processing of grains and legumes suggests to us that we may have
      in hand a relatively quick, inexpensive, and highly sensitive assay that
      identifies individuals at increased risk for the development of lymphoid
      malignancy. The generation of this assay evolved from our interest in the causes
      and consequences of lymphocyte-specific chromosomal aberration.

PMID- 1394172
TI  - Follicular dendritic cells: B-cell proliferation and maturation.
AB  - Follicular dendritic cells (FDC) play a pivotal role in the initiation and
      maintenance of the secondary humoral immune response. FDC located in the
      follicles of secondary lymphoid tissues are part of a special mechanism that
      handles antigen in a specific antibody-rich environment and are integral members
      of the antigen transport cell-FDC-iccosome-B-cell axis that leads to the
      formation of germinal centers, antibody-forming cells, and memory B-cells. This
      review briefly outlines the basic biology of FDC function and provides a source
      of pertinent references.

PMID- 1394171
TI  - Antigen selection in human lymphomagenesis.
AB  - Although surface immunoglobulin plays a central role in the differentiation and
      growth of normal B-cells, its role in the growth of human B-cell malignancies is
      largely a matter of conjecture. Human follicular lymphomas are attractive systems
      to study in part because they are clones of cells sharing many similarities with
      germinal center B-cells which are critically dependent on antigen selection for
      survival. Nucleotide sequence information was determined for the immunoglobulin
      heavy chain variable genes expressed by two cases of follicular lymphoma. In
      addition, the germ line variable gene counterparts were also cloned and sequenced
      from biopsy material obtained from both of these patients. Numerous mutations
      from germ line were present in the variable genes from both of these cases, many
      of which accumulated during expansion and growth of these lymphomas. Moreover,
      the mutations that accumulated during tumor expansion were distributed in a
      manner that almost certainly was dependent on positive selection presumably
      mediated by contact with an antigen. These data indicate that antigen selection
      is probably important for the growth and clonal evolution of follicular
      lymphomas.

PMID- 1394173
TI  - The past is prologue: use of serum banks in cancer research.
AB  - In this paper, we emphasize the uses of serum banks in cancer research. These
      include not only case/control studies but also prospective seroepidemiological
      studies in which the development of a serological marker, such as a viral
      antibody or viral antigen, can be correlated with the subsequent development of
      cancer in either an active surveillance program or the use of cancer registries
      or hospital records. Several different methods of application of the cohort
      technique are illustrated by studies of hepatitis B antigen and hepatocellular
      carcinoma and of Epstein-Barr virus in relation to African Burkitt's lymphoma,
      Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Collections of sera done for one
      purpose can often be utilized for another purpose, if properly stored and
      documented. Two examples are tests for human T-cell leukemia virus, type 1,
      antibody from sera done for a health survey in Barbados approximately 8 years
      earlier and the use of data determined for a prospective study of the incidence
      of Epstein-Barr virus infection and infectious mononucleosis in West Point Cadets
      for psychological factors affecting the development of clinical illness among
      those infected. Archival materials, such as frozen tissues and paraffin sections,
      may also now be utilized for identifying genomes of potential oncogenic viruses
      by the polymerase chain reaction.

PMID- 1394174
TI  - Applications of experimental techniques to epidemiological studies of non
      Hodgkin's lymphoma: use of archival tissues.
AB  - Archival tissues, particularly formalin-fixed paraffin-embedded tumors, have
      become increasingly valuable in studies of the etiology of cancer. In non
      Hodgkin's lymphoma, subclassification of tumors by immunophenotyping and
      identification of oncogenic viruses has allowed more accurate interpretation of
      associated epidemiological information. One such example is adult T-cell
      leukemia/lymphoma, which is not a single histopathological entity and usually is
      associated with human T-cell lymphotropic virus, type I. In addition to
      confirming the diagnosis, the pattern of virus distribution, utilized recently in
      studies of Epstein-Barr virus and human herpesvirus-6-associated lymphoma, has
      suggested which tumors are more likely to have the virus playing a passenger role
      (virus detected in uninvolved tissues) and in which tumors the virus may have an
      etiological role (virus restricted to tumor cells). Preservation and cataloguing
      of tumors and relevant clinical and demographic data may play an increasingly
      important role in demographic studies.

PMID- 1394175
TI  - Quantification of the impact of known risk factors on time trends in non
      Hodgkin's lymphoma incidence.
AB  - The incidence of non-Hodgkin's lymphoma among white men in the United States was
      measured as 6.9/100,000 person-years in 1947-1950 and as 17.4 in 1984-1988. We
      have estimated how much the known and suspected diagnostic and risk factors might
      have contributed to this apparent increase of 152%. Firm conclusions cannot be
      drawn without more data on risk and changes in prevalence, but a reasonable range
      of impacts can be constructed. After accounting for the likely effects of
      misdiagnosis of Hodgkin's disease as non-Hodgkin's lymphoma, of the acceptance of
      new entities of non-Hodgkin's lymphoma, of familial factors, of human
      immunodeficiency virus and other immunosuppressive conditions or drugs, and of
      occupation, we estimate that the percentage increase in incidence was still 80%
      among all males and 42% among those aged 0-64. An agent carrying a relative risk
      of 2.0 rising in prevalence from 0 to 42% would account for the latter rise.
      Diet, hair dyes, and general environmental exposures to pesticides may be
      contributing, but currently estimated risks and changes in exposure levels do not
      appear large enough to account for the residual rise. Among men aged 75-84, some
      of the residual rise of 109% probably is diagnostic, but only further research
      will clarify the issue.

PMID- 1394176
TI  - The emerging epidemic of non-Hodgkin's lymphoma: current knowledge regarding
      etiological factors. Time trends and pathological classification: a summary.

PMID- 1394177
TI  - The emerging epidemic of non-Hodgkin's lymphoma: current knowledge regarding
      etiological factors. Research directions and general discussion: a summary.

PMID- 1394178
TI  - The emerging epidemic of non-Hodgkin's lymphoma: current knowledge regarding
      etiological factors. Molecular and immunoregulatory mechanisms: a summary.

PMID- 1394179
TI  - Conclusion/perspective I--National Cancer Institute Workshop on the emerging
      epidemic of non-Hodgkin's lymphoma: current knowledge regarding etiological
      factors.

PMID- 1394180
TI  - Conclusion/perspective II--National Cancer Institute Workshop on the emerging
      epidemic of non-Hodgkin's lymphoma: current knowledge regarding etiological
      factors.

PMID- 1394181
TI  - Aspirin and the potential role of prostaglandins in colon cancer.

PMID- 1394182
TI  - The effect of an amino acid-lowering diet on the rate of melphalan entry into
      brain and xenotransplanted glioma.
AB  - Melphalan (L-phenylalanine mustard, L-PAM, alkeran; molecular weight, 305,000) is
      transported across tumor cell membranes and the blood-brain barrier by the large
      neutral amino acid (LNAA) transport system. Normally, plasma LNAA levels are high
      enough and the affinity low enough that this system does not transport much
      melphalan into the brain. However, plasma amino acids can be reduced by fasting
      and protein-free diet. We used this method to reduce competition and to increase
      melphalan transport into brain tumors. In nude mice fasted for 12 h and then fed
      a protein-free diet for 2 and 6 h, mean plasma LNAA levels were 46% and 42% of
      control values. Nude mice with xenotransplanted D-54MG human gliomas were used to
      study tissue distribution and uptake kinetics of [3H]melphalan in a control group
      and a diet group (after a 12-h fast and 2 h of a 0% protein diet). The K1 (blood
      to-tissue transfer constant) of melphalan, determined by graphical analysis and
      by nonlinear fitting to a 2-compartment model, was higher in the diet group in
      all tumor regions except the necrotic center of subcutaneous tumors; the increase
      was significant in the tumor periphery of brain and s.c. tumors. The ratio of K1s
      (diet to control) varied from 1.2 to 1.3 in brain tumors, 1.9 to 2.1 in
      subcutaneous tumors, and 1.8 to 3.1 in tumor-free brain. The apparent
      [3H]melphalan distribution space was significantly higher in the tumor periphery
      of both brain and subcutaneous tumors of the 15- and 30-min diet group. We also
      measured blood-brain barrier transport of [alpha-14C]aminoisobutyric acid and
      blood flow (with [131I]iodoantipyrine): the K1 of [alpha-14C]aminoisobutyric acid
      was 28.1 +/- 6.6 (SE) in brain tumors and 24.3 +/- 8.9 microliters/g/min in
      subcutaneous tumors. Blood flow was 58.2 --> 3.9 in brain tumors and 5.2 +/- 0.4
      ml/100 g/min in subcutaneous tumors. Fasting, when combined with a protein-free
      diet, reduces plasma amino acid levels and thereby reduces competition between
      melphalan and LNAAs. This may increase the amount of melphalan that can enter a
      brain tumor without increasing the administered drug dose and suggests a
      therapeutic manipulation that can be used to increase the delivery of melphalan.

PMID- 1394183
TI  - Modulation of protein kinase C-epsilon by phorbol esters in the monoblastoid U937
      cell.
AB  - Expression of protein kinase C-epsilon was examined in the human monoblastoid
      U937 cell. This cell type contained the alpha, beta, and epsilon isoforms of
      protein kinase C (PKC). While PKC-epsilon content was slightly higher in the
      cytosolic than in the particulate fraction, the amount contained in the
      particulate fraction was higher than the alpha and beta isoforms which were
      predominantly localized to the cytosol. After an acute exposure to tetradecanoyl
      13-phorbol acetate (TPA), PKC-epsilon translocated to the particulate fraction.
      Acute or chronic exposure to ionomycin did not alter content of the epsilon
      isoform. Longer exposures to TPA decreased PKC-epsilon in both cellular
      fractions. PKC-epsilon displayed a similar sensitivity to TPA-induced down
      regulation as did PKC-beta while PKC-alpha was more resistant to this effect.
      After a 72-h exposure to 0.1 nM TPA, increases in the alpha and beta isoforms but
      not in PKC-epsilon were observed. However, 1,25-dihydroxy vitamin D3 and
      dibutyryl cyclic AMP which induce U937 differentiation enhanced PKC-epsilon
      expression.

PMID- 1394184
TI  - Antilymphoma activity of human gamma delta T-cells in mice with severe combined
      immune deficiency.
AB  - Human Burkitt lymphoma (Daudi) cells grow as disseminated tumors in mice with
      severe combined immune deficiency (SCID) after either i.v. or i.p. injection.
      These cells are lysed in vitro by human V gamma 9/V delta 2 T-cells that
      recognize the groEL homologue on the Daudi cell surface. We report that both
      Daudi cell-stimulated peripheral blood mononuclear cells (Daudi-PBMC) containing
      41-95% of V gamma 9/V delta 2 T-cells and V gamma 9/V delta 2 T-cell clones
      prolong the survival of SCID mice given inoculations of a lethal dose of Daudi
      cells. Groups of 6-8-week-old SCID mice were given inoculations i.v. or i.p. of
      10(5) Daudi cells followed (through different injection sites) by: (a) 10(7)
      Daudi-PBMC; or (b) 10(7) unstimulated PBMC; or (c) 0.9% saline solution. All
      animals in groups (b) and (c) died of disseminated lymphoma, and their survival
      was significantly shorter than that of mice in group (a) (P < 0.001 for both i.v.
      and i.p. routes). Significant antitumor effects were also detected when Daudi
      PBMC were injected 4 days before or 4 days after Daudi cells (P < 0.05). In vivo
      depletion of murine natural killer cells by anti-asialo GM-1 rabbit antiserum did
      not affect survival, suggesting that these cells did not contribute to lymphoma
      killing. Daudi-PBMC did not exert in vivo antitumor activity against the control
      Raji lymphoma. Mice receiving i.p. injections of Daudi cells followed by
      cytotoxic V gamma 9/V delta 2 T-cell clones also survived significantly longer (P
      < 0.05 for 3 different clones) than animals given Daudi cells alone or Daudi
      cells followed by noncytotoxic gamma delta T-cell clones. Our results indicate
      that this model system can be used for studies of human antilymphoma T-cell
      responses in vivo.

PMID- 1394185
TI  - Genotoxicity of environmental agents in human mammary epithelial cells.
AB  - Despite an increasing incidence of human breast cancer, its etiology remains
      unknown. Since some environmental chemicals are stored in human breast fat and
      are rodent mammary carcinogens, determining the genotoxic potential of
      environmental agents in this key target tissue is important. An assay was
      developed for detecting genotoxic activity, as unscheduled DNA synthesis (UDS),
      induced by chemicals and UV radiation in early passage cultures of normal human
      mammary epithelial cells (HMEC) derived from 5 different women. In order to
      measure UDS in culture, reduction in the percentage of cells in S-phase was
      accomplished either by depriving the cells of epidermal growth factor and bovine
      pituitary extract or by contact inhibition of growth. Cultures were incubated
      with test chemicals for 24 h in the presence of [3H]-thymidine. UDS was
      quantitated autoradiographically as net grains per nucleus (nuclear grains minus
      cytoplasmic background, population average) with > or = 6 net nuclear grains
      considered in repair for any individual cell. A positive response was observed
      with UV radiation, benzo(a)-pyrene, aflatoxin B1, ethylmethanesulfonate, 1,6
      dinitropyrene, 2-acetylaminofluorene, and tobacco smoke condensate but not 7,12
      dimethylbenz(a)anthracene or 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results
      demonstrate that HMEC from all 5 women examined have the ability to metabolize a
      variety of environmental chemicals to DNA-reactive forms. Furthermore, some
      chemicals known either to cause mammary cancer in rodents or to be contaminants
      in human breast tissue are genotoxic in HMEC. A positive response in passage 9
      cultures was observed only with direct acting agents, suggesting that HMEC may
      lose their metabolic capabilities in longer-term cultures. The HMEC UDS assay may
      be used to address the role of environmental agents in human breast cancer by
      determining whether chemicals are DNA reactive or metabolized to DNA reactive
      species in this critical target tissue.

PMID- 1394186
TI  - DNA strand breaks and DNA cross-links in peripheral mononuclear blood cells of
      ovarian cancer patients during chemotherapy with cyclophosphamide/carboplatin.
AB  - DNA strand breaks and DNA cross-links were detected in peripheral mononuclear
      blood cells of 15 ovarian carcinoma patients by alkaline filter elution. These
      patients received therapy with 600 mg/m2 of cyclophosphamide and 350 mg/m2 of
      carboplatin. Blood samples were taken a day before and 16 to 18 h after a therapy
      cycle. The patients showed an increased elution rate of 37% compared with that of
      healthy controls before the current cycle of chemotherapy, probably due to
      treatment in a previous cycle of therapy. The difference was statistically
      significant (P < 0.02; U test). At the end of the actual cycle of therapy an
      average acceleration of the elution rate of 157% was found compared with that of
      controls (P < 0.01; U test). Compared with the rate before the cycle of therapy,
      the mean elution rate after treatment was accelerated by 89% (P < 0.01; Wilcoxon
      test). The amount of DNA-protein cross-links was also increased after drug
      application. The individual patients showed different responses after drug
      intake. While some patients showed hardly any alteration in the elution rate,
      others showed an acceleration of up to 400%. Monitoring the course of disease in
      six of these patients indicated that a strong acceleration in the elution rate
      after drug application is possibly linked to the success of the chosen cancer
      treatment as measured by a decrease in the tumor marker CA12-5 to the normal
      level. In another investigation the group of patients who had received non
      alkylating antineoplastic agents showed no increase in DNA strand breaks compared
      with untreated controls. Thus, monitoring DNA single-strand breaks in the
      peripheral mononuclear blood cells of patients can help to evaluate the
      efficiencies of the cancer treatment as a composite of individual differences in
      resorption, metabolic activation and detoxification, and possibly some
      constitutional aspects of drug resistance to cyclophosphamide/cisplatin and
      probably to several other alkylating antineoplastic drugs. This may help in
      choosing an effective drug and in adjusting the doses of these drugs individually
      in the chemotherapy of cancer.

PMID- 1394187
TI  - Proposed role of phosphatidic acid in the extracellular control of the transition
      from G2 phase to mitosis exerted by epidermal growth factor in A431 cells.
AB  - Epidermal growth factor (EGF) has been shown to cause an inhibition of A431 cells
      in G2 phase within approximately 10 min, i.e., shortly before mitosis (Kinzel et
      al., Cancer Res., 50: 7932-7936, 1990). This system has been used to study the
      proposed role phospholipid metabolites, particularly phosphatidic acid (PA), may
      play (Kaszkin et al., Cancer Res., 51: 4328-4335, 1991) in the extracellular
      control of cells at the physiological restriction site in G2 phase. A431 cells
      responded to EGF with a dose-dependent formation of phosphatidic acid (PA) which
      correlated with the dose-dependent G2 delay as well as with their time courses.
      The G2 delay induced by EGF as well as PA mobilization were effected in
      conditioned medium or in fresh medium containing bovine serum albimun instead of
      serum, i.e., under the conditions necessary for precursor studies to be carried
      out. The major pathway of PA formation was probably via phospholipase C-mediated
      breakdown of phosphatidylinositol and diacylglycerol kinase: (a) the dose
      response of PA formation correlated with that of total inositol phosphate
      accumulation; (b) little diacylglycerol was found and then only at a high EGF
      concentration; (c) prelabeling with [1-14C]arachidonic acid resulting in a large
      specific labeling of phosphatidylinositol led to an EGF-induced, dose-dependent
      formation of radioactive arachidonyl-PA (correlated with that of total PA and
      inositol phosphate), but in the presence of a primary alcohol not to the
      formation of radioactive phosphatidylalcohol; (d) prelabeling with [1-14C]oleic
      acid led to the EGF-induced formation of labeled PA, which in the presence of a
      primary alcohol was only slightly reduced to the advantage of very low levels of
      labeled phosphatidyl alcohol, thus demonstrating that an EGF-effected activation
      of phospholipase D did occur but contributed little to the general PA level. An
      alternative mobilization of PA was attempted with the phorbolester 12-O
      tetradecanoylphorbol-13-acetate (TPA), which was shown to activate phospholipase
      D in A431 cells and to elicit PA from a phospholipid pool which was not
      significantly labeled with radioactive arachidonic acid. The TPA-induced degree
      of PA formation and of the G2 delay correlated. Both phenomena were considerably
      larger with fresh medium containing 0.5% bovine serum albumin instead of serum
      than in conditioned medium.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1394188
TI  - Chemoprevention of colon carcinogenesis by the synthetic organoselenium compound
      1,4-phenylenebis(methylene)selenocyanate.
AB  - The chemopreventive effect of 40% and 80% maximum tolerated dose (MTD) levels of
      1,4-phenylenebis(methylene)selenocyanate (p-XSC) administered in the diet during
      the initiation phase (2 weeks before, during, and up to 3 days after carcinogen
      administration) and the post-initiation phase (3 days after carcinogen treatment
      until termination) of azoxymethane (AOM)-induced colon carcinogenesis was studied
      in male F344 rats. The MTD of p-XSC was determined in male F344 rats and found to
      be 50 ppm. Beginning at 5 weeks of age, all animals were divided into various
      experimental groups (42 rats/group) and fed the high-fat semipurified diet or
      diets containing 20 (40% MTD) and 40 (80% MTD) ppm p-XSC. At 7 weeks of age, all
      animals (30 rats/group) except the vehicle-treated groups (12 rats/group) were
      administered s.c. injections of AOM (15 mg/kg body weight/week for 2 weeks).
      Three days after the second injection of AOM or vehicle (normal saline), groups
      of animals fed the p-XSC diets and control diet were transferred, respectively,
      to control diet and p-XSC diets and continued on these diets until the
      termination of the study. All animals were necropsied during the 36th week after
      AOM treatment. Colonic mucosal prostaglandin E2 and selenium-dependent
      glutathione peroxidase were measured in animals fed the control and p-XSC diets
      at the termination of the study. The results indicate that 40 ppm p-XSC
      administered during the initiation phase significantly inhibited the colon tumor
      incidence (percentage of animals with tumors). Dietary p-XSC administered at 20
      and 40 ppm levels during the initiation phase significantly inhibited colon tumor
      multiplicity (tumors/animal and tumors/tumor-bearing animal). Colon tumor
      incidence and multiplicity were significantly reduced in groups fed 20 and 40 ppm
      p-XSC diets at the postinitiation phase of carcinogenesis. Colonic mucosal
      selenium-dependent glutathione peroxidase activity was increased, and
      prostaglandin E2 was reduced in animals fed the p-XSC diet compared to animals
      fed the control diet. Whereas the precise mechanisms of p-XSC-induced inhibition
      of colon carcinogenesis remain to be elucidated, it is likely that the effect
      during the initiation and postinitiation phases may be due to alteration in
      carcinogen metabolism and to modulation of prostaglandin synthesis and selenium
      dependent glutathione peroxidase activity.

PMID- 1394189
TI  - Reversal of basic fibroblast growth factor-mediated autocrine cell transformation
      by aromatic anionic compounds.
AB  - NIH-3T3 cells transfected with basic fibroblast growth factor (bFGF) fused to a
      signal peptide sequence (spbFGF cells) are transformed in vitro and tumorigenic
      in vivo. Treatment of spbFGF cells with low and nontoxic concentrations (0.5-2.5
      micrograms/ml) of negatively charged, nonsulfated aromatic compounds (e.g., aurin
      tricarboxylic acid, 4-hydroxyphenoxyacetic acid) resulted in restoration of their
      normal proliferative rate, morphological appearance, and adhesion properties.
      Binding and cross-linking experiments using 125I-labeled bFGF revealed that these
      alterations were associated with an up-regulation of high affinity receptors bFGF
      receptors was induced by these compounds in spbFGF cells that were seeded on
      fibronectin to enforce a firm cell attachment and flattening. Thus, induction of
      spbFGF cell adhesion and spreading may not be related to restoration of normal
      bFGF-receptor interactions. Although the negatively charged aromatic compounds
      mimic many of the effects of heparin in other systems (e.g., release of heparin-
      and heparan sulfate-bound proteins, inhibition of heparanase), heparin, heparan
      sulfate, and dextran sulfate were not effective at the low concentrations of the
      anionic compounds used in the present study. Likewise, suramin, a sulfated
      aromatic molecule, was effective at toxic concentrations, 400-600-fold higher
      than the nonsulfated aromatic compounds. The development of defined, nontoxic
      anionic compounds may provide a new strategy to interfere with the autonomous and
      anchorage independent mode of cell growth involved in autocrine cell
      transformation and cancer.

PMID- 1394191
TI  - Sequence specificity of aflatoxin B1-induced mutations in a plasmid replicated in
      xeroderma pigmentosum and DNA repair proficient human cells.
AB  - The mutagenic spectrum induced by aflatoxin-DNA lesions in DNA repair deficient
      and repair proficient human cells was investigated. The reactive metabolite
      aflatoxin B1-8,9-epoxide was synthesized and reacted in vitro with the shuttle
      vector plasmid pS189. Plasmids were transfected into human fibroblasts and
      allowed to replicate, and the recovered plasmids were screened in indicator
      bacteria for plasmid survival and mutations in the supF marker gene. Sequence
      data were obtained from 71 independently arising mutants recovered from DNA
      repair deficient xeroderma pigmentosum (XP) cells [XP12BE(SV40)] and 60 mutants
      recovered from a DNA repair proficient cell line (GM0637). Plasmid survival was
      lower and mutation frequency higher with the XP cells, and the mutation hotspots
      differed substantially for the 2 cell lines. Most mutations (> 90%) were base
      substitutions at G:C pairs, only about one-half of which were G:C-->T:A
      transversions, the expected predominant mutation. One-third of the mutations at
      GG sites and none of those at isolated Gs were G:C-->A:T transitions. Tandem base
      substitutions also occurred only at GG sites and were found only with XP cells.
      The location of mutation hotspots with either cell line did not correlate with
      the level of modification within the sequence as assessed by a DNA polymerase
      stop assay. These results suggest that the DNA repair deficiency associated with
      XP can influence not only the overall frequency of mutations but also the
      distribution of mutations within a gene. The finding of transition mutations
      exclusively at GG sites may be of predictive value in attempts to link dietary
      aflatoxin exposure to cancers associated with specific mutations in the c-ras
      oncogene and the p53 tumor suppressor gene.

PMID- 1394190
TI  - Immunization of colorectal cancer patients with modified ovine submaxillary gland
      mucin and adjuvants induces IgM and IgG antibodies to sialylated Tn.
AB  - Tn and sialylated Tn (sTn) are blood group-related epitopes expressed on mucins
      of colon carcinoma and other epithelial tumors and are, therefore, potential
      targets for immunological control. We have immunized 20 colorectal cancer
      patients at high risk for recurrence with a vaccine consisting of partially
      desialylated ovine submaxillary gland mucin (modified OSM) which contains both Tn
      and sTn determinants. Six patients were treated with modified OSM alone (group
      1), eight patients were treated with modified OSM and the immunological adjuvant
      DETOX (group 2), and six patients were treated with modified OSM and Bacillus
      Calmette-Guerin (group 3). Pre- and postvaccination sera were tested by enzyme
      linked immunosorbent assay and dot blot immune stains for antibodies reactive
      with modified OSM. Antibody titers increased in 4 of 8 patients immunized with
      modified OSM and DETOX, in 5 of 6 patients immunized with modified OSM and B.
      Calmette-Guerin, and in 0 of 6 patients receiving modified OSM without adjuvant.
      The specificity of induced IgM and IgG antibodies was confirmed by demonstrating
      reactivity with OSM, bovine submaxillary mucin, and synthetic glycoconjugates sTn
      human serum albumin (HSA) and Tn-HSA in enzyme-linked immunosorbent assay and
      immune stains. Median IgM pre-postvaccination reciprocal titers were 20/80 for Tn
      HSA and 10/320 for sTn-HSA. Low level IgG antibody titers against sTn-HSA were
      detected after vaccination in 7 patients. Toxicity was limited to inflammatory
      skin reactions at the site of vaccination resulting from the adjuvants. No
      inflammatory infiltrates were seen in the skin when the modified OSM vaccine was
      administered in the absence of an immunological adjuvant. These results
      demonstrate that sTn and Tn can be recognized by the human immune system and that
      vaccines containing these structures can be administered safely with
      immunological adjuvants. Attempts to augment the immunogenicity of these
      carbohydrate antigens by covalent attachment to immunogenic carrier proteins and
      the use of more potent immunological adjuvants are now being pursued.

PMID- 1394192
TI  - A region of antisense RNA from human p120 cDNA with high homology to mouse p120
      cDNA inhibits NIH 3T3 proliferation.
AB  - The human nucleolar p120 protein is a proliferation-associated antigen which is
      expressed in G1 and peaks during the early S phase of the cell cycle.
      Overexpression of the human p120 protein caused the transformation of NIH 3T3
      cells and expression of an antisense p120 construct inhibited the growth of NIH
      3T3 cells (Perlaky et al., Cancer Res., 52:428-436, 1992). The middle region of
      the antisense p120 RNA was found to be almost as inhibitory as the full length
      antisense construct but the 5' and 3' antisense portions did not affect NIH 3T3
      cell proliferation. After the mouse p120 complementary DNA was cloned and
      sequenced, comparison with the human p120 complementary DNA showed a striking
      conservation of 85% of the nucleotide sequence and 96% of the amino acid
      sequence. The two ends of the p120 molecule had less homology in their nucleotide
      and amino acid sequences. Based on this homology, the observed inhibitory effects
      of the middle portion of antisense human p120 RNA may be related to suppression
      of mouse p120 expression by RNA:RNA duplex formation. The high evolutionary
      conservation of the middle region suggests it has a critical role for the
      function of this protein.

PMID- 1394193
TI  - Lethality, DNA alkylation, and cell cycle effects of adozelesin (U-73975) on
      rodent and human cells.
AB  - Adozelesin (U-73975) is an extremely potent cytotoxic agent which causes 90%
      lethality, after 2 h exposure in vitro, of Chinese hamster ovary and lung (CHO
      and V79), mouse melanoma (B16), and human ovarian carcinoma (A2780) cells at
      0.33, 0.19, 0.2, and 0.025 ng/ml, respectively. Under similar conditions,
      Adriamycin and cisplatin had 90% lethality values in CHO cells of 150 ng/ml (=
      249 nM) and 6800 ng/ml (= 2266 nM), respectively. The relative drug sensitivity
      of the cell lines (A2780 > V79, B16, CHO) was correlated to the relative amounts
      of [3H]adozelesin alkylated to DNA. The greater sensitivity of A2780 was due to
      (a) greater DNA alkylation at different drug doses and (b) greater intrinsic
      sensitivity of A2780 which resulted in greater cell kill at comparable DNA
      alkylation. Phase specific toxicity studies show that adozelesin was least lethal
      to CHO cells in mitosis and very early G1. Lethality increased as cells
      progressed through G1 and was maximal in late G1 and early S. Mitotic cells had
      lower drug uptake and correspondingly less drug binding to DNA than G1 or S-phase
      cells. However, based on the amount of drug alkylated per micrograms of DNA,
      cells in M, G1, and S were equally sensitive. Therefore, the lower sensitivity of
      M-phase cells was due to lower drug uptake. Adozelesin had three different
      effects on progression of CHO, V79, B16, and A2780 through the cell cycle: (a)
      slowed progression through S which resulted in significantly increasing the
      percentage of S-phase cells. This effect was transient; (b) cell progression was
      blocked in G2 for a long time period; (c) the response of the cell lines to the
      G2 block differed. CHO and V79 cells escaped G2 block by dividing and entered the
      diploid DNA cycle or did not undergo cytokinesis and became tetraploid. On the
      contrary, B16 and A2780 cells remained blocked in G2 and did not become
      tetraploid. Cell progression was inhibited in a similar manner when a
      synchronized population of M, G1, or S-phase cells were exposed to adozelesin.

PMID- 1394194
TI  - Antitumor effects of a bispecific antibody targeting CA19-9 antigen and CD16.
AB  - Bispecific murine monoclonal antibodies that target tumor and Fc gamma RIII
      (CD16) can promote relevant tumor lysis by large granular lymphocytes. For these
      antibodies to be clinically useful, their properties should be maintained in
      vivo, where competing human immunoglobulin, shed target antigen, and shed CD16
      may be encountered. At a minimum, bispecific antibody antitumor effects should be
      preserved in whole blood. Furthermore, potentiation of tumor lysis should be
      reflected by demonstrating the ability of bispecific antibody-retargeted effector
      cells to infiltrate and mediate lysis of organized tumor. If these
      characteristics are demonstrated, and there is evidence of in vivo efficacy of
      bispecific antibody-based therapy in a relevant animal model, further clinical
      development of such antibodies would be warranted. In this report the ability of
      CL158 bispecific antibody supernatants to mediate lysis of SW948 tumor growing in
      monolayer is shown to be preserved in the presence of interleukin 2-activated
      whole blood. When SW948 cells were grown in vitro as multicellular human tumor
      spheroids, incubation with interleukin 2-activated lymphocytes (LAK cells) and
      CL158 led to structural and widespread necrosis. This was dependent on CL158 and
      resistant to competition by pooled human immunoglobulin or interleukin 2-exposed
      whole blood. These effects were not promoted by the monospecific antibodies
      produced by the parent clones of CL158 and were not observed when the IgG2a
      variant of CA19-9 antibody, which mediates conventional antibody-dependent
      cellular cytotoxicity, was used instead of its bispecific derivative. To examine
      the efficacy of bispecific antibody-based treatments on in vivo tumor, scid mice
      bearing early s.c. SW948 xenografts were treated with interleukin 2 for 5
      consecutive days, supplemented by three i.v. injections of 10(7) human LAK cells
      and various antibodies. Treatment of mice bearing SW948 tumors with LAK cells did
      not retard tumor growth, but when CL158 was added, significant delays in tumor
      growth were observed. Tumor growth delay required treatment with both LAK cells
      and the bispecific antibody. Treatment with the IgG2a variant of CA19-9 antibody,
      alone or with LAK cells, had no effects on tumor growth. Although the mechanisms
      of these antitumor effects require further study, it is clear that human LAK cell
      treatment of animals bearing early, established s.c. tumors is enhanced by the
      addition of bispecific antibodies with relevant binding characteristics. When
      compared with the IgG2a isotype variant of CA19-9 monoclonal antibody, this
      bispecific antibody offers the advantages of preservation of activity in
      physiological conditions, infiltration and disruption of organized tumor in
      vitro, and antitumor effects in a relevant xenograft model.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1394195
TI  - Synchronization of breast cancer cell proliferation in vivo by combined hormonal
      and polyamine manipulation.
AB  - Optimal synchronization of breast cancer cell proliferation by hormonal means may
      be limited by cellular heterogeneity in sensitivity to the multistep activation
      of growth following initial hormone binding to the receptor. We hypothesized that
      induced synchronous growth may be improved by combined manipulation of the
      polyamine (PA) pathway since we have previously shown that PAs are distal
      effectors of hormonal action on proliferation in breast cancer. To test our
      hypothesis, we induced an initial phase of hormone and PA depletion (castration
      plus administration of the PA synthesis inhibitor alpha-difluoromethylornithine)
      in rats bearing N-nitrosomethylurea induced mammary tumors. This was followed by
      transition phase of hormone repletion in the presence of alpha
      difluoromethylornithine (to push the cells into the proliferative cascade up to
      the distal step controlled by PA) and finally a phase of hormone and PA
      repletion. Simultaneously, groups of rats were subjected to hormone/PA
      depletion/repletion individually. The effects of these manipulations on the
      labeling indices (LIs) of glandular, myoepithelial, and nonepithelial cells were
      estimated by autoradiography. The combined hormone/PA manipulation yielded the
      highest degree of synchronization with LIs of the glandular and myoepithelial
      cells being approximately 2-fold over intact control after only 2 or 3 days of
      combined repletion. In contrast, hormone treatment alone restored the LIs of
      glandular cells only to control levels and minimally influenced those of
      myoepithelial cells. PA manipulation alone failed to affect the LIs of any cell
      type. Although the rate of tumor regrowth was highest with the combination
      treatment, the absolute tumor volumes did not differ significantly at the end of
      the repletion phase between the three regimens. These results indicate that
      combined hormone/PA manipulation provides the best "therapeutic window" (LI/tumor
      volume) for implementation of kinetically based cytotoxic chemotherapy.

PMID- 1394196
TI  - Glycosylation pathways in the biosynthesis of gangliosides in melanoma and
      neuroblastoma cells: relative glycosyltransferase levels determine ganglioside
      patterns.
AB  - In order to elucidate some of the factors that determine the characteristic
      expression of gangliosides in malignant melanoma and neuroblastoma the levels of
      ganglioside synthases (glycosyltransferases) were determined in a panel of cell
      lines from those tumors that exhibited a wide range of ganglioside composition.
      Sialyltransferases (GM3, GD3, GD1a, and GT1b synthases), N
      acetylgalactosaminyltransferases (GM2 and GD2 synthases), and
      galactosyltransferase (GM1 and GD1b synthases) were analyzed in crude membrane
      preparations from these cells. The results confirmed the importance of GM3 and
      GD3 synthases in determining the prominence of the a (GM3 to GT1a) or b (GD3 to
      GQ1b) biosynthetic pathways. The overall ganglioside composition in cells was
      found to be dependent on the relative levels of specific enzymes acting
      sequentially or in competing pathways. In general, the pattern and levels of
      transferases correlated with the actual ganglioside content of the cell line,
      although several important discrepancies were noted. For example, in cell lines
      containing high amounts of GD2 ganglioside, the level of the preceding enzyme in
      the pathway (GD3 synthase) was unexpectedly low. Thus, the high GD2:GD3 ratios
      characteristic of most neuroblastomas result from low levels of GD3 synthase as
      well as high levels of GD2 synthase. In other cell lines, GD3 synthase was
      completely absent, resulting in the synthesis of GM2, but not GD2, by N
      acetylgalactosaminyltransferase I, as would be expected. It was concluded that
      different glycosyltransferases play key roles in determining glycolipid
      expression in different cell types.

PMID- 1394197
TI  - Incidence of c-Ki-ras activation in N-methyl-N-nitrosourea-induced mammary
      carcinomas in pituitary-isografted mice.
AB  - We found previously that mouse mammary epithelial cells cultured in the presence
      of the mammogenic hormones progesterone and prolactin and treated with the
      carcinogen N-methyl-N-nitrosourea produced a high frequency of hyperplastic
      alveolar nodules and carcinomas with squamous metaplasia upon transplantation to
      syngeneic mice. The majority of these mammary transformants had an activated c-Ki
      ras proto-oncogene with a specific point mutation in codon 12 (G35 to A35). To
      determine whether these in vitro findings parallel mammary carcinogenesis in
      vivo, virgin female mice were pituitary isografted to increase their circulating
      levels of progesterone and prolactin. The pituitary isograft results in an
      increase in proliferation, leading to lobulo-alveolar development and
      differentiation of the mammary epithelial cells. Five weeks after pituitary
      isografting, the mice were treated with a single injection of N-methyl-N
      nitrosourea (50 micrograms/g body weight). Greater than 90% of the N-methyl-N
      nitrosourea-treated mice developed mammary carcinomas between 3 and 7 months
      after treatment. The majority (75%) of the carcinomas had histopathology
      identical to that of tumors induced in vitro in the presence of progesterone and
      prolactin. A number of the mammary cancers (17%) induced in pituitary-isografted
      mice also had the identical point mutation in the c-Ki-ras proto-oncogene found
      in the in vitro studies. These results suggest that the hormonal milieu around
      the time of carcinogen exposure affects not only the incidence and phenotype of
      the mammary transformants but also the molecular events associated with mammary
      carcinogenesis.

PMID- 1394198
TI  - Stage-specific expression of cancer-associated type 1 and type 2 chain
      polylactosamine antigens in the developing pancreas of human embryos.
AB  - Expression of type 1 and type 2 chain carbohydrate antigens during the course of
      morphogenesis of human embryonic pancreas was investigated using specific
      monoclonal antibodies and compared with the carbohydrate antigen profiles of
      human pancreatic cancers. The type 2 chain antigens, such as stage-specific
      embryonic antigen 1 (Le(x)) and I-antigens, appeared much earlier than the type 1
      chain antigens; the epithelial cells of primitive foregut were Le(x)+I-antigen-
      in the embryos at Carnegie stages 16-23, while the pancreatic primordial cells,
      which had differentiated from the Le(x)+ gut epithelial cells, were Le(x)-I
      antigen+ at Carnegie stages 22-23. The type 1 chain antigens, such as Le(a),
      Le(b), Le(c), and their sialylated derivatives, were not expressed in any cells
      at these stages and appeared much later in the pancreas of the 10-12-week
      embryos, when the primitive pancreatic ductal cells in the primordia exhibited an
      extensive budding of the daughter cells. At this stage, Le(a) appeared and was
      expressed strongly in the epithelial cells of primitive pancreatic ducts as well
      as in the daughter cells that were destined to differentiate into future
      centroacinar cells; Le(b) was localized in the daughter cells which were to
      become future acinar cells; and Le(c) was specifically expressed in the daughter
      cells which were to form future Langerhans islets. With regard to the sialylated
      derivatives of Le(a), expression of the 2-3 sialyl Le(a) antigen was limited to
      the epithelial cells of the primitive pancreatic ducts, while the 2-6 sialyl
      Le(a) antigen was strongly expressed in the future centroacinar cells, which had
      differentiated from the corresponding daughter cells. Among these antigens, the
      Le(a) and 2-3 sialyl Le(a) antigens showed the highest incidence in human
      pancreatic cancer tissues. These results indicate that the expression of these
      carbohydrate antigens in embryonic pancreas is differentiation dependent and cell
      lineage specific and that most human pancreatic cancer cells mimic the
      carbohydrate antigen profile of the epithelial cells of the primitive pancreatic
      ducts in human embryos.

PMID- 1394200
TI  - Perioperative immunotherapy with recombinant interleukin 2 in patients undergoing
      surgery for colorectal cancer.
AB  - Major surgery impairs the cellular immune response. We have therefore studied the
      immunological effects of low-dose recombinant interleukin 2 given to patients
      undergoing surgery for colorectal cancer to determine whether this agent has
      potential in perioperative adjuvant immunotherapy. Patients were randomly
      allocated to control (n = 13) or treatment groups (n = 12). Immunological studies
      of both lymphocyte function and subset number were performed preoperatively and
      on Days 1, 4, 7, and 10. Treatment with recombinant interleukin 2 prevented the
      postoperative fall in both natural killer and lymphokine-activated killer cell
      cytotoxicity, clearly demonstrated in the control group. The treatment group also
      showed in vivo T-cell activation with an initial lymphopenia followed by a
      rebound lymphocytosis and upregulation of the subset markers CD25 (interleukin 2
      receptor) and CD45RO (T-memory cells). These combined effects may have important
      consequences in controlling metastatic dissemination of tumor during the
      vulnerable perioperative period.

PMID- 1394199
TI  - Estrogen receptor-directed radiotoxicity with Auger electrons: specificity and
      mean lethal dose.
AB  - To assess the feasibility of using estrogen receptor-directed therapy with Auger
      electron-emitting ligands for therapy of estrogen receptor (ER)-containing
      cancers, we synthesized and evaluated the radiotoxicity of several 123I-labeled
      estrogens to specifically kill ER+ cells in culture. Auger electrons have been
      previously shown to be of short range, generally less than the dimensions of a
      cell, so that to use them therapeutically a mechanism is needed to deliver the
      Auger electron-emitting nuclide to the vicinity of the DNA. Since it is now well
      established that the estrogen receptor, when bound to estrogen, forms a high
      affinity association with distinct estrogen response elements in the DNA, we
      wished to test the hypothesis that a short exposure of cells to a 123I-labeled
      estrogen would be specifically radiotoxic to ER+ cells, and that the decays per
      cell needed for cell killing would be compatible with reasonable levels of
      receptor occupancy. Using the halodestannylation reaction with tributyl tin
      precursors of several estrogens and commercially available iodine-123, we
      prepared the iodoestrogens, E-17 alpha(-)[123I]-iodo-11 beta-methoxyestradiol and
      2(-)[123I]iodo-1,1-bis(4-hydroxyphenyl)--2-phenylethylene, at high specific
      activities, in several cases at essentially the specific activity of 123I itself,
      240,000 Ci/mmol. When various concentrations of either of the 123I-labeled
      estrogens were incubated for 1 h with a subline of ER+ Chinese hamster ovary
      cells and the washed cells plated for survival assays, a dose-dependent,
      unlabeled estradiol-inhibitable reduction in survival was observed. In contrast,
      Chinese hamster ovary cells not expressing estrogen receptor showed little
      sensitivity to the radiotoxicity of the 123I-labeled estrogens. Calculations
      based on the assayed residence time of the iodoestrogens in the cells indicate
      that several hundred decays per cell are sufficient to kill cells.

PMID- 1394201
TI  - Cadherin dysfunction in a human cancer cell line: possible involvement of loss of
      alpha-catenin expression in reduced cell-cell adhesiveness.
AB  - A human lung cancer cell line, PC 9, was analyzed to elucidate the molecular
      mechanisms of dysfunction of cadherin-mediated cell-cell adhesion in cancer.
      Although PC 9 cells strongly expressed E-cadherin at the cell membrane, which was
      indistinguishable immunochemically from functional E-cadherin, they did not show
      tight cell-cell adhesion and had reduced E-cadherin-mediated aggregation
      activity. Immunoprecipitation with E-cadherin and Western blot analysis revealed
      that PC 9 cells did not express alpha-catenin, a cadherin-associated protein,
      suggesting that this was the cause of the cadherin dysfunction in the cell line.
      In addition, Northern and Southern blot analyses disclosed homozygous deletion of
      part of the alpha-catenin gene, which might have resulted in the loss of alpha
      catenin expression in PC 9 cells.

PMID- 1394203
TI  - Absence of HSP28 synthesis and phosphorylation during the development of chronic
      thermotolerance in murine L929 cells.
AB  - We investigated the correlation between chronic thermotolerance development and
      phosphorylation, synthesis, or expression of the HSP28 family in murine L929
      cells. Chronic thermotolerance developed during heating at 41.5 degrees C as
      indicated by a biphasic survival curve. However, heat-induced phosphorylation of
      HSP28 was not detected. Furthermore, we failed to detect HSP28 synthesis during
      chronic heating by using two-dimensional polyacrylamide gel electrophoresis. The
      lack of HSP28 synthesis was also confirmed in acute thermotolerance. Similar
      results were observed in NIH 3T3 cells. Although Southern blots clearly
      demonstrated the presence of the HSP28 gene in genomic DNA, Northern blots failed
      to demonstrate its expression. Unlike HSP28, the expression of constitutive and
      inducible HSP70 genes, along with the synthesis of their proteins, were
      stimulated during chronic heating at 41.5 degrees C in L929 cells. These results
      suggest that HSP28 synthesis and its phosphorylation are not required to develop
      both chronic and acute thermotolerance in L929 cells.

PMID- 1394202
TI  - Phase II trial of suramin in patients with advanced renal cell carcinoma:
      treatment results, pharmacokinetics, and tumor growth factor expression.
AB  - Twenty-six patients with advanced renal cell carcinoma were treated with suramin
      administered by continuous infusion, with dosing determined by a nomogram. One
      patient achieved a partial response and five patients achieved a minor response
      or had stable disease for > 3 months. Toxicities included an immune-mediated
      thrombocytopenia in one patient and Staphylococcus sepsis that was not associated
      with neutropenia in five patients. Pharmacokinetic parameters were determined by
      the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit
      using a two-compartment open model and first-order rate elimination. This showed
      a wide interpatient variation in time to target level (median, 13.8 days), volume
      of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The
      patients who achieved a partial response, minor response, or stable disease had a
      slower elimination rate of suramin, compared to patients with progressive
      disease. Tumor specimens were obtained prior to therapy and were analyzed for the
      production of five different growth factor-specific RNA transcripts. These
      included transforming growth factor alpha, acidic fibroblast growth factor, basic
      fibroblast growth factor, and platelet-derived growth factor types A and B. No
      difference in the pattern of growth factor expression was seen in tumors of
      responding and nonresponding patients. Suramin does not have significant
      antitumor activity in renal cell carcinoma. The wide variability in
      pharmacokinetics suggests that individual dosing should be used in future trials
      of suramin for treatment for other malignancies. Pertinent corollary studies of
      tumor biology and clinical pharmacology should be included whenever possible in
      clinical trials in patients with renal cell carcinoma.

PMID- 1394204
TI  - Inhibitory effect of 2-deoxy-D-glucose on liver tumor growth in rats.
AB  - Since tumor cells are more dependent on glycolysis for energy supply than other
      cells, we tested whether its inhibition by 2-deoxy-D-glucose (2-DG) affects tumor
      growth. Male Wistar rats were inoculated in the liver with tumor cells from a
      chemically induced colonic adenocarcinoma. From day 5 after inoculation 2-DG (400
      mg/kg/24 h) was continuously infused into the hepatic artery for 5 days; controls
      received saline in the same fashion. Seven days after the end of infusion, the
      animals were sacrificed. A second experimental group of rats was treated with
      isolated liver perfusion for 30 min with oxygenated blood through the portal vein
      and hepatic artery simultaneously. In the perfusate, 400 mg/kg 2-DG were added,
      and the rats were sacrificed at 10 days after perfusion. A first control group
      underwent perfusion without 2-DG, and a second control group received i.v.
      infusion of 2-DG (400 mg/kg/30 min) for 30 min over 5 days. A nontreated control
      group was also added. All animals survived the procedures. The concentration of
      blood glucose increased in the rats receiving 2-DG i.v. and intraarterially but
      was unchanged in the other groups. The tumor growth was significantly reduced by
      2-DG in all experimental groups, with no difference between the groups. It is
      therefore concluded that 2-DG is of potential interest in the treatment of
      malignancies. Since local application of 2-DG avoids the risk for systemic side
      effects, this approach should be explored further.

PMID- 1394205
TI  - Gene-specific oligonucleotide probes for alpha, mu, pi, and microsomal rat
      glutathione S-transferases: analysis of liver transferase expression and its
      modulation by hepatic enzyme inducers and platinum anticancer drugs.
AB  - Glutathione S-transferases (GSTs) play an important role in the detoxification of
      diverse electrophilic chemicals, including anticancer drugs. Gene-specific
      oligonucleotide probes were developed to monitor the expression of individual GST
      mRNAs in livers of adult male rats treated with drugs and other chemical
      modulators of GST expression. Northern blot analysis of total liver RNA using
      probes specific for individual GSTs belonging to classes alpha (GSTs Ya1, Ya2,
      Yc), mu (GSTs Yb1, Yb2, Yb3), pi (GST Yp), and GSTms demonstrated the expression
      in liver of all but Yp mRNA. Kidney GST expression was at least as high as that
      in liver for GSTs Ya1, Yc, and Yp, while it was substantially lower but still
      detectable for GSTs Ya2, Yb2, and GSTms. Several of the liver GST class alpha
      mRNAs, in particular Ya2, were inducible by pretreatment of rats with
      phenobarbital or isosafrole. In contrast, dexamethasone preferentially induced
      Yb1, Yb2, and Ya2, while two other inducers of liver drug metabolism, isoniazid
      and clofibrate, were less effective with respect to GST induction. GSTms mRNA was
      induced to a small extent or not at all by the agents tested. Treatment of adult
      male rats with the anticancer drug cisplatin increased liver expression of GST Yc
      mRNA and suppressed Ya1 mRNA levels with little or no major effect on several
      other GST mRNAs. Western blot analysis of liver cytosols prepared from the
      cisplatin-treated rats revealed corresponding changes in GST Yc and Ya protein
      levels. Comparable changes in liver GST Ya1 and Yc expression were effected by
      the cisplatin analogue iproplatin but not by carboplatin or transplatin. This
      pattern of response to these platinum drugs is comparable to that seen with
      respect to platinum drug-induced gonadal toxicity and modulation of liver
      cytochrome P450 expression, suggesting a common mechanistic basis for these
      diverse effects of platinum anticancer drugs on hepatic enzymes of drug
      metabolism. Together, these studies demonstrate the utility of oligonucleotide
      probes for phenotyping liver tissue for the expression of GST enzymes that can
      contribute to anticancer drug metabolism and resistance. They also raise the
      possibility of drug-drug interactions involving cisplatin and alkylating agent
      anticancer drugs that can be metabolized in liver by alpha-class GSTs.

PMID- 1394206
TI  - Inhibition of cell attachment by selenite.
AB  - Brief pre-exposure of HeLa cells to micromolar concentrations of selenite
      resulted in a dose-dependent decrease in the rate of their subsequent attachment
      to a solid matrix (tissue culture dish). Similar low concentrations of selenite
      also inhibited colony formation, but only when the cells were exposed prior to
      their attaching to the dish, not when they were exposed after attachment. This
      indicates that inhibition of cell proliferation by selenite requires exposure to
      higher concentrations for longer periods of time. In contrast, selenate,
      selenomethionine, selenocystine, and sulfite did not affect cell attachment, even
      at significantly higher concentrations. Thus, the inhibition of cell attachment
      is a specific effect of selenite. Selenite also inhibited the attachment of cells
      to bacteriological dishes coated with fibronectin, laminin, or collagen, proteins
      that are components of the extracellular matrix. There was no inhibition when the
      tissue culture dishes or the protein-coated dishes were pre-exposed to selenite.
      There was also no inhibition when the cells were exposed to selenite during the
      attachment process. Thus, pre-exposure of the cells to selenite was necessary for
      inhibition of attachment. Since cell attachment has been shown to be an important
      early step in tumor cell invasion and metastasis, these results suggest a novel
      mechanism of the anticarcinogenic effect of selenite: inhibition of the
      attachment of tumor cells to the extracellular matrix.

PMID- 1394207
TI  - Expression level of the nm23 gene in clonal populations of metastatic murine and
      human neoplasms.
AB  - The purpose of this study was to determine whether nm23 steady-state mRNA
      expression levels correlate with metastatic potential of mouse K-1735 melanoma
      cells, human KM12 colon cancer cells, and human SN12 renal cancer cells. Since
      neoplasms are heterogeneous and contain subpopulations of cells with different
      metastatic potentials, we analyzed multiple sets of nonmetastatic and metastatic
      clones isolated from each neoplasm. In addition, we also examined nine somatic
      cell hybrids produced by the fusion of nonmetastatic and metastatic K-1735
      clones. In the mouse melanoma, we found heterogeneity in nm23-1 steady-state
      expression levels among the clones and hybrids that did not correlate with their
      metastatic phenotype. Clones isolated from human colon or renal carcinomas
      expressed similar levels of nm23-HI regardless of metastatic potential in nude
      mice. All of the human tumor cells were heterozygous for the nm23-HI-specific
      allelic DNA fragments, with no allelic deletions or gross alterations detected.
      Since the failure of tumor cells to produce metastasis can be due to multiple
      deficiencies, these data stress the importance of using independent clones with
      different metastatic potentials for the analysis of gene regulation of this
      process.

PMID- 1394208
TI  - Fine-scale deletion mapping of the distal long arm of chromosome 6 in 70 human
      ovarian cancers.
AB  - To define a small region on chromosome 6q containing a putative tumor suppressor
      gene for ovarian cancer, we examined loss of heterozygosity in 70 ovarian tumors
      of three histological types with nine restriction fragment length polymorphism
      markers located at 6q24-27. Among 33 cancers of serous type that were informative
      at one or more loci, 17 showed allelic loss at a few or all loci examined,
      whereas only 1 of 15 mucinous-type tumors and 2 of 12 clear-cell tumors revealed
      loss of heterozygosity. This result supported our earlier suggestion that
      alteration of a gene on chromosome 6q may play an important role during
      development of serous ovarian tumors (Sato et al., Cancer Res., 51: 5118-5122,
      1991). Frequent losses were observed between loci defined by CI6-119 (D6S195) at
      6q26 and CI6-49 (D6S161) at 6q27. A detailed deletion map indicated a commonly
      deleted region between loci defined by CI6-111 (D6S193) and CI6-24 (D6S149);
      these two markers are estimated to be 1.9 cM apart on the basis of linkage
      analysis. Our results further define a region containing a tumor suppressor gene
      involved in ovarian carcinoma within an approximately 2-megabase-long segment of
      chromosome 6q.

PMID- 1394209
TI  - Effective alpha-particle-mediated radioimmunotherapy of murine leukemia.
AB  - The specificity, toxicity, and efficacy of alpha-particle-mediated
      radioimmunotherapy of murine erythroleukemia was assessed by use of tumor
      specific monoclonal antibody 103A labeled with 212Bi. Forty % of the injected
      dose/g tissue targeted to neoplastic spleens within 1 h after i.v. injection.
      When 212Bi-103A was injected on day 13 of disease, a dose-dependent response was
      achieved, as measured by a reduction in splenomegaly and absence of liver
      metastasis. Mice treated with 212Bi-103A on day 8 of disease showed no
      histological evidence of erythroleukemia on day 22 and survived significantly
      longer (median, 118 days) than mice treated with 212Bi-control IgG (78 days) or
      untreated mice (63 days), indicating successful specific radioimmunotherapy.

PMID- 1394210
TI  - Isolation of a prostate carcinoma cell proliferation-inhibiting factor from human
      seminal plasma and its similarity to transforming growth factor beta.
AB  - Human seminal plasma (SP) has been known to contain both growth-inhibitory and 
      stimulatory factors. We attempted to identify a factor that inhibited DNA
      synthesis in some metastatic prostate cancer cell lines. The SP factor was
      sensitive to digestion by trypsin, but its activity increased after boiling or
      dialysis against 1 M acetic acid, by 3- to 4-fold. The SP factor was partially
      purified using a cation-exchange resin. Apparent molecular mass determination by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed it to be a
      M(r) 25,000 protein, and M(r) 13,000 after reduction. This protein strongly
      inhibited DNA synthesis in two metastatic androgen-independent human prostatic
      carcinoma cell lines (PC3 and DU145) and the Dunning R3327G rat prostatic
      adenocarcinoma. It was ineffective on androgen-dependent LNCaP cells. The
      proliferation-inhibiting activity of this SP protein was specifically and
      completely abolished by a neutralizing anti-transforming growth factor beta (TGF
      beta) antiserum. Furthermore, immunoblot analysis using the anti-TGF-beta
      antiserum showed the similarity of this protein to TGF-beta. The maximum
      concentration of this protein in SP was 165 +/- 11.7 ng/ml (mean +/- SD), of
      which only one-fourth may be present in active form under normal conditions.
      Identification of a TGF-beta-like protein in SP might also explain the variety of
      growth and immune modulation properties of human SP.

PMID- 1394211
TI  - Structure and expression of human Fli-1 gene.
AB  - Three ets family members, v-ets, spleen focus forming virus proviral integration
      1/Pu.1, and Friend leukemia integration 1 (Fli-1), were shown to be involved in
      retroviral mediated acute leukemias suggesting that ets family members play a
      crucial role in transformation. Mouse Fli-1 was shown to be involved in 75%
      erythroleukemias induced by Friend murine leukemia virus suggesting the
      possibility that Fli-1 may play a critical role in cellular transformation. Since
      Fli-1 maps to the mouse chromosome region syntenic with human chromosome 11q23
      24, it is tempting to speculate that human Fli-1 may be involved in human
      sarcomas, leukemias, and lymphomas involving human chromosome 11q23-24. We have
      isolated complementary DNA clones representing the human homologue of Fli-1 gene.
      Nucleotide sequence analysis revealed that the human Fli-1 gene codes for a 452
      residue protein the predicted amino sequence of which shows 80% homology to the
      human erg-2 protein previously described. A 3.5-kilobase transcript of the human
      Fli-1 gene was observed in different cells. Sequence analysis revealed two
      domains of ets homology, one at the 5' and the other at the 3' end of the Fli-1
      gene. This 3'-ets homology domain, which is mainly responsible for DNA binding
      activity, is seen in all the ets family members; however, the 5'-ets homology
      region is conserved in only five genes, Fli-1, c-ets-1, ets-2, GABP-alpha, and
      erg, suggesting a common biological function which is shared among these genes.
      Interestingly, mouse and human Fli-1 transcripts contain highly homologous 5'
      untranslated region suggesting that this conserved region may play an important
      role in the posttranscriptional regulation of the Fli-1 transcript.

PMID- 1394212
TI  - Pharmacokinetic analysis of the perivascular distribution of bifunctional
      antibodies and haptens: comparison with experimental data.
AB  - A mathematical model is developed to describe the concentration profiles around
      individual tumor blood vessels for two-step approaches to cancer treatment. The
      model incorporates plasma pharmacokinetics, interstitial diffusion, reversible
      binding between antibody and hapten and between antibody and tumor-associated
      antigens, and physiological parameters to evaluate present experimental
      approaches and to suggest new guidelines for the effective use of two-step
      approaches. Results show considerable interaction between the binding kinetics,
      initial drug doses, and antigen density, with optimal parameter ranges depending
      on the desired goal: treatment or detection. The hapten concentration in tumors
      was found to be nonuniform because of specific binding to antibodies. While
      binding of the hapten to the bifunctional antibody is necessary for improved
      retention, too large a binding affinity may lead to very poor penetration of the
      hapten into regions far away from blood vessels. The time delay between antibody
      and hapten injection was found to be an important parameter. Longer time delays
      were found to be advantageous, subject to constraints such as internalization of
      the antibody and tumor growth during treatment. A proper combination of initial
      doses for the two species was also seen to be crucial for maximum effectiveness.
      Comparison of the model with the experimental data of Le Doussal et al. (Cancer
      Res., 51: 6650-6655, 1991) and Stickney et al. (Cancer Res., 50: 3445-3452, 1990)
      suggests two novel, yet testable, hypotheses: (a) the early pharmacokinetics of
      low molecular weight agents can have an important effect on later concentrations
      using two-step approaches; and (b) metabolism may play an important role in
      reducing concentrations in the tumor and tumor:plasma concentration ratios. These
      results should help in the effective design of two-step strategies.

PMID- 1394213
TI  - Tumor cell surface-associated binding site for the M(r) 72,000 type IV
      collagenase.
AB  - We have studied the capacity of two human breast adenocarcinoma cells, MDA-MB231
      and MCF-7, to bind exogenous M(r) 72,000 type IV collagenase by both
      morphological and radioreceptor binding assays. By indirect immunofluorescence,
      staining with a specific anti-M(r) 72,000 type IV collagenase antibody was
      strongly induced when cells were preincubated with the purified enzyme. Scatchard
      plot analysis indicated the existence of a binding site for the M(r) 72,000 type
      IV collagenase with high affinity for both cell lines (Kd = 2 x 10(-9) M). These
      results are the first demonstration of the existence of a tumor cell membrane
      associated putative receptor for a member of the matrix metalloproteinase family,
      as previously evidenced for the urokinase-type plasminogen activator.

PMID- 1394214
TI  - Distribution of cells expressing myc proteins in human colorectal epithelium,
      polyps, and malignant tumors.
AB  - The myc gene family encodes nuclear phosphoproteins that are thought to play a
      role in the control of cellular proliferation and differentiation. We have
      undertaken an immunohistochemical study assessing the expression of myc gene
      family proteins in individual cells of normal colonic mucosa, colorectal polyps,
      and colorectal adenocarcinomas. We screened a panel of mouse monoclonal
      antibodies that we raised against recombinant human c-myc and N-myc proteins for
      recognition of myc proteins in paraffin tissue sections. Two of these antibodies,
      H120C69 and H8C150, were selected for indirect immunoperoxidase staining of
      tissue sections from 16 normal mucosas, 24 polyps, and 30 adenocarcinomas. In
      normal colon, about 25% of the cells in the lower one-third of the crypts of
      Lieberkuhn stain for myc-related protein. This distribution resembles that of
      proliferating cells in the crypt. Benign hyperplastic polyps resemble normal
      mucosa in their myc staining pattern, with about 25% of the cells positive. In
      adenomatous polyps, the putative precursors of adenocarcinomas, from 50 to 100%
      of the cells stain positively for myc protein. In these cases, stained cells
      extend to the luminal surface, consistent with the previously reported expansion
      of the proliferation zone in these lesions. All adenocarcinomas examined had
      increased levels of myc protein relative to normal mucosa. The tumor cells
      exhibited markedly heterogeneous myc staining patterns, both among different
      tumors and, in some cases, within a single tumor. Comparison with Ki-67
      monoclonal antibody staining indicates that myc protein expression in many tumors
      is uncoupled from cellular proliferation. Surprisingly, we observed increased
      numbers of myc-expressing cells and increased levels of myc protein in
      histologically normal colon directly adjacent to tumor, suggesting that many
      colorectal carcinomas secrete growth factors that activate gene expression in
      neighboring normal mucosa.

PMID- 1394215
TI  - A comparison of the abilities of nitrobenzylthioinosine, dilazep, and
      dipyridamole to protect human hematopoietic cells from 7-deazaadenosine
      (tubercidin).
AB  - Nitrobenzylthioinosine, dilazep, and dipyridamole are potent inhibitors of
      equilibrative transport of nucleosides that may have pharmacological applications
      in modulating the therapeutic index of nucleoside antimetabolites used in cancer
      chemotherapy. We have compared the relative abilities of these inhibitors to
      reduce the toxicity of in vitro exposures to tubercidin against clonogenic
      progenitor cells of normal human bone marrow (CFU-GEMM, BFU-E, CFU-GM) and of two
      leukemic human cell lines (HL-60/C1, CCRF-CEM) that differ in their expression of
      transporter subtypes. Short (1-h) exposures to 1 microM tubercidin alone
      inhibited colony formation (a) of normal human hematopoietic progenitors (CFU
      GEMM, BFU-E, CFU-GM) by 100%, and (b) of HL-60/C1 and CCRF-CEM cells by > 90%.
      Pretreatment (30 min) with nitrobenzylthioinosine, dilazep, or dipyridamole
      followed by simultaneous treatment (1 h) with these transport inhibitors during
      tubercidin exposures reduced toxicity against hematopoietic progenitors and cell
      lines. Greater reductions of toxicity were consistently seen with bone marrow
      progenitors and CCRF-CEM cells than with HL-60/C1 cells. For CFU-GEMM, BFU-E, and
      CFU-GM cells, reductions in tubercidin toxicity of 50-100% were achieved at these
      concentrations: > or = 0.1 microM (nitrobenzylthioinosine); > or = 0.1 microM
      (dilazep); and > or = 3.0 microM (dipyridamole). Pretreatment (30 min) followed
      by simultaneous treatment (1 h) with any of the transport inhibitors (> or = 0.1
      microM) and 0.1 microM [3H]-tubercidin blocked the uptake of radioactivity
      completely in CCRF-CEM cells and only partially in HL-60/C1 cells. These effects,
      which were consistent with the nucleoside transport phenotypes of CCRF-CEM cells
      (inhibitor-sensitive) and HL-60/C1 cells (inhibitor-sensitive and inhibitor
      resistant), suggested that protection was due to the inhibition of tubercidin
      uptake via equilibrative nucleoside transport system(s). Light-density
      mononuclear cells from human bone marrow, of which the clonogenic progenitors
      represented only a minor (< 0.01%) subpopulation, possessed far fewer
      nitrobenzylthioinosine-binding sites (2 x 10(4) sites/cell, Kd = 0.7 nM) than
      either HL-60/C1 cells (1.7 x 10(5) sites/cell, Kd = 0.9 nM) or CCRF-CEM cells
      (3.3 x 10(5) sites/cell, Kd = 0.5 nM). Initial rates of uptake of 1 microM
      [3H]adenosine (0-6 s, 20 degrees C) by human bone marrow mononuclear cells were
      reduced partially by 0.1 microM inhibitor (nitrobenzylthioinosine > dipyridamole
      > dilazep) and completely by 10 microM inhibitor.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1394216
TI  - Epidermal growth factor receptor monoclonal antibody inhibits constitutive
      receptor phosphorylation, reduces autonomous growth, and sensitizes androgen
      independent prostatic carcinoma cells to tumor necrosis factor alpha.
AB  - Results of recent studies indicate that cultured, androgen-independent prostatic
      carcinoma cells synthesize and secrete transforming growth factor alpha, which
      interacts with epidermal growth factor receptors (EGFRs) to promote autonomous
      growth. In the present study, we evaluated the expression and constitutive
      activation of EGFRs in normal prostatic epithelial cells and the androgen
      independent prostatic carcinoma cell lines PC3 and DU145. Our studies showed that
      cultured normal epithelial cells and androgen-independent prostatic carcinoma
      cells actively synthesize and exhibit constitutive phosphorylation of the M(r)
      170,000 EGFR. The addition of monoclonal anti-EGFR reduced receptor
      phosphorylation and significantly inhibited the proliferation of prostatic tumor
      cells. The observed reduction in EGFR phosphorylation could be partially
      attributed to an antibody-induced decrease in the expression of metabolically
      labeled EGFR. Results of further studies showed that anti-EGFR enhanced the
      sensitivity of PC3 cells to the cytotoxic and cytostatic effects of tumor
      necrosis factor alpha. These studies demonstrate that constitutive activation of
      EGFR in androgen-independent prostatic carcinoma plays a functional role in the
      regulation of cellular proliferation in vitro. In addition, the enhanced
      sensitivity of prostatic carcinoma cells to tumor necrosis factor alpha in the
      presence of anti-EGFR provides a rationale for the further investigation of
      combination therapy in the treatment of disseminated, androgen-independent
      disease.

PMID- 1394217
TI  - Time dependence of DNA lesions and growth inhibition by ICI D1694, a new
      quinazoline antifolate thymidylate synthase inhibitor.
AB  - DNA single-strand breaks and associated growth inhibition induced by the
      thymidylate synthase inhibitor N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazoline-6
      ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid (ICI D1694) were
      quantitated using the human ileocecal adenocarcinoma cell line, HCT-8. The
      effects of different concentrations and schedules of [6R,S]-5
      formyltetrahydrofolate ([6RS]LV) and 2'-deoxy-thymidine (dThd) on drug growth
      inhibition and DNA damage were also evaluated. The drug concentrations for 50%
      inhibition of cell growth in culture following 2-h and 72-h exposures were 0.073
      and 0.003 microM, respectively. After a 2-h drug exposure, the occurrence of DNA
      single-strand breaks (SSBs) was time dependent. It was detectable at 8 h and
      reached a maximum at about 24 h, 34 +/- 3 (SD) and 305 +/- 34 rad equivalents
      with 0.1 microM (50% inhibition concentration) and 1.0 microM (90% inhibition
      concentration) ICI D1694, respectively. A significant level of DNA SSBs (101 +/-
      13 rad equivalents) was still detectable at 72 h after the 2-h treatment with 1
      microM ICI D1694. No significant level of DNA SSBs was detected when cells were
      exposed simultaneously to ICI D1694 and 20 microM [6RS]LV. Complete rescue of
      drug-induced DNA SSBs could be achieved when cells were exposed to 10 microM dThd
      starting no later than 4 h after drug treatment. The growth inhibition of ICI
      D1694 was abrogated by [6RS]LV in a concentration-dependent manner. Complete
      protection was achieved when cells were exposed simultaneously to 1 microM ICI
      D1694 and 5 microMs [6RS]LV or to 3 microMs dThd immediately after drug
      treatment. The results demonstrate that: (a) the growth inhibition of ICI D1694
      is a function of time and schedule; (b) the growth inhibition is accompanied by
      extensive DNA single-strand breaks and slow repair; (c) at 1 microM ICI D1694, 3
      microMs dThd and 5 microMs [6RS]LV can completely rescue cells from drug effects
      when dThd is added up to 4 h following drug treatment or when [6RS]LV is given in
      combination with the drug; (d) interference of [6RS]LV with ICI D1694 action may
      be occurring at the level of drug uptake and at intracellular targets, while dThd
      interferes with the drug action at intracellular targets.

PMID- 1394218
TI  - Cytotoxicity of CD3-ricin A chain immunotoxins in relation to cellular uptake and
      degradation kinetics.
AB  - The cytotoxicity of WT32 (CD3)-ricin A immunotoxin (IT) to the acute
      lymphoblastic leukemia T-cell line Jurkat was compared with the rate of
      internalization and intracellular degradation of WT32 and WT32-ricin A during
      continuous exposure. Moreover, the influence of NH4Cl and monensin on these
      processes was studied. Based on protein synthesis inhibition ([3H]leucine
      incorporation), it appeared that cytotoxicity was not fully expressed directly
      after exposure to IT due to a delay in either the internalization of membrane
      bound IT or the action of intracellular ricin A. Varying the duration of
      incubation and postponing [3H]leucine addition for up to 24 h after initiation
      showed that cytotoxicity occurred in two phases, rapid internalization of
      initially bound IT followed by a continuous but slower uptake, possibly due to
      reexpression of the CD3 antigen. No differences were found in the rate of
      internalization and degradation of 125I-labeled WT32 and WT32-ricin A.
      Internalization started rapidly after binding at 37 degrees C, was fastest during
      the first 12 h (+/- 360,000 molecules/cell), and continued for at least 24 h (+/-
      420,000 molecules/cell). Exocytosis of intracellularly degraded molecules became
      measurable after 1 to 2 h of incubation at 37 degrees C and increased to
      approximately 400,000 molecules/cell in 24 h. After 4 h of incubation at 37
      degrees C the number of internalized molecules exceeded the amount of WT32 that
      could maximally bind to the cell membrane (+/- 150,000 molecules/cell),
      confirming reexpression of antigen. The addition of NH4Cl and monensin enhanced
      the cytotoxicity of WT32-ricin A, probably due to an increased intracellular
      amount of IT. These agents appeared to reduce strongly the degradation of
      internalized WT32, resulting in an accumulation of intracellular molecules. NH4Cl
      was most effective during the first 12 h of incubation, whereas monensin
      increased the amount of intracellular WT32 molecules after 2 to 24 h. Our
      observations suggest that incubation conditions for the optimal cytotoxicity of
      IT treatment can be predicted by studying the internalization and degradation of
      the IT or respective monoclonal antibody.

PMID- 1394219
TI  - Phase I and endocrine study of exemestane (FCE 24304), a new aromatase inhibitor,
      in postmenopausal women.
AB  - Aromatase inhibitors are a useful therapeutic option in the management of
      endocrine-dependent advanced breast cancer. A single-dose administration of
      exemestane (FCE 24304; 6-methylenandrosta-1,4-diene-3,17-dione), a new
      irreversible aromatase inhibitor, was investigated in 29 healthy postmenopausal
      female volunteers. The compound, given at p.o. doses of 0.5, 5, 12.5, 25, 50,
      200, 400, and 800 mg (n = 3-4), was found to be a well tolerated, potent, long
      lasting, and specific inhibitor of estrogen biosynthesis. The minimal dose which
      produced the maximum suppression of plasma estrogens was 25 mg, reducing plasma
      estrone, estradiol, and estrone sulfate to 35, 28, and 39% of basal values,
      respectively. This maximum suppression, observed at 3 days, persisted for at
      least 5 days after administration of a single dose. However, there was no
      interference on cortisol, aldosterone, 17-hydroxyprogesterone, or
      dehydroepiandrostenedione sulfate plasma levels. Peak plasma exemestane
      concentrations of 27, 221, 343, and 414 ng/ml were reached within 2 h after
      administration of 50, 200, 400, and 800 mg, respectively. Plasma concentrations
      declined rapidly and fell under the detection limit (10 ng/ml) at 4 (50 mg) or 24
      h (200 and 400 mg). No clinically significant adverse events which could be
      attributed to the drug were reported. Apart from transient eosinophilia in 3
      patients, all biochemical and hematological laboratory parameters were within
      1.25-fold of the normal ranges.

PMID- 1394221
TI  - A murine model for antibody-directed targeting of vascular endothelial cells in
      solid tumors.
AB  - An attractive approach to the therapy of solid tumors would be to target
      cytotoxic agents or coagulants to the vasculature of the tumor rather than to the
      tumor cells themselves. This strategy has 3 advantages: (a) it should be
      applicable to many types of solid tumors because all require a blood supply for
      survival and growth; (b) the target endothelial cells are directly accessible
      through the blood and are normal cells, making the outgrowth of resistant mutants
      unlikely; and (c) there is an in-built amplification mechanism because thousands
      of tumor cells are reliant on each capillary for nutrients and oxygen. Despite
      its theoretical attractions, the approach of tumor vascular targeting has not
      been testable because antibodies that recognize tumor vascular endothelial cell
      antigens with adequate specificity are currently not available. In this study, we
      developed a model system in which to investigate the antibody-directed targeting
      of vascular endothelial cells in solid tumors in mice. A neuroblastoma
      transfected with the mouse interferon-gamma gene, C1300(Mu gamma), was grown in
      antibiotic-treated BALB/c nude mice. The interferon-gamma secreted by the tumor
      induces the expression of major histocompatibility complex Class II antigens on
      the tumor vascular endothelium. Class II antigens are absent from the vasculature
      of normal tissues, although they are present on B-lymphocytes, cells of
      monocyte/macrophage lineage, and some epithelial cells. Anti-Class II antibody
      administered i.v. strongly stains the tumor vasculature, whereas an antitumor
      antibody directed against a major histocompatibility complex Class I antigen of
      the tumor allograft produces classical perivascular tumor cell staining. This
      model should enable the theoretical superiority of tumor vascular targeting over
      conventional tumor cell targeting to be tested.

PMID- 1394220
TI  - Phase II preclinical drug screening in human tumor xenografts: a first European
      multicenter collaborative study.
AB  - In a European joint project carried out in 6 laboratories a disease-oriented
      program was set up consisting of a panel of 7 tumor types, each represented by 4
      to 8 different human tumor lines, for secondary screening of promising anticancer
      drugs. Human tumor lines were selected on the basis of differences in histology,
      growth rate, and sensitivity to conventional cytostatic agents. Xenografts were
      grown s.c. in nude mice, and treatment was started when tumors reached a mean
      diameter of 6 mm in groups of mice where at least 6 tumors were evaluable. Drugs
      were given at the maximum tolerated dose. For evaluation of drug efficacy, median
      tumor growth curves were drawn, and specific growth delay and treated/control x
      100% were calculated. Doxorubicin (8 mg/kg i.v. days 1 and 8) was effective
      (treated/control < 50%, and specific growth delay > 1.0) in 0 of 2 breast
      cancers, 1 of 3 colorectal cancers, 2 of 5 head and neck cancers, 3 of 6 non
      small cell lung cancers, 4 of 6 small cell lung cancers, 0 of 3 melanomas, and 3
      of 6 ovarian cancer lines. Amsacrine (8 mg/kg i.v. days 1 and 8) was not
      effective, while datelliptium (35 mg/kg i.p. days 1 and 8) was active against 2
      of 6 small cell lung cancer lines. Brequinar sodium (50 mg/kg i.p. days 1-5)
      showed efficacy in 4 of 5 head and neck cancers, 5 of 8 non-small cell lung
      cancers, and 4 of 5 small cell lung cancer lines. The project has been shown to
      be a feasible approach. Clinical activity for doxorubicin and inactivity for
      amsacrine against solid tumor types was confirmed in the human tumor xenograft
      panel. Additional anticancer drugs will be studied in the European joint project
      to further define the reliability of this novel, promising screening approach.

PMID- 1394222
TI  - Receptors for interleukin 2 on human squamous cell carcinoma cell lines and tumor
      in situ.
AB  - Several human head and neck squamous carcinoma cell lines were found to bind 125I
      labeled or fluorescein-labeled interleukin 2 (IL-2). This binding was inhibited
      by an excess of cold ligand, IL-2, and by anti-p55 and anti-p70 monoclonal
      antibodies to the alpha and beta chains, respectively, of the IL-2 receptor (IL
      2R). A small number (300/cell) of high-affinity IL-2R (2 x 10(-12) M) and a
      larger number (> 13,000/cells) of intermediate-affinity IL-2R (3 x 10(-10) M)
      were present on these tumor cells. By affinity cross-linking, tumor cells were
      shown to bind 125I-IL-2 to a M(r) 66,000 and 55,000 doublet peptide. The alpha
      and beta chains of the IL-2R also were detected on the surface of cultured tumor
      cells using the relevant monoclonal antibodies and flow cytometry.
      Immunoperoxidase staining with anti-p70 monoclonal antibody confirmed the
      expression of IL-2R on squamous cell carcinomas of the head and neck in situ. The
      presence of transcripts for p55/IL-2R-alpha and p70/IL-2R-beta in PCI-1 cells was
      confirmed by the polymerase chain reaction followed by hybridization to the IL-2R
      alpha complementary DNA probe or IL-2R-beta complementary DNA probe,
      respectively. Our observations demonstrate that intermediate-affinity and high
      affinity IL-2Rs are expressed on some human squamous cell carcinomas of the head
      and neck and that the receptors are functional, because growth of these tumor
      cell lines can be directly inhibited by exogenously supplied IL-2. The presence
      of IL-2R on human solid tumors could be important to consider, in addition to
      immunomodulatory effects of IL-2, in developing optimal therapeutic strategies
      for the administration of IL-2 to patients with cancer.

PMID- 1394223
TI  - Mucin gene expression in colonic tissues and cell lines.
AB  - Complementary DNA clones encoding four different mucin core peptides have been
      isolated. However, the expression of these mucin genes in the colon has not been
      systematically studied. The present investigation used Northern blot analysis to
      study the expression of MUC1, MUC2, MUC3, and MUC4 mRNA in paired normal and
      cancerous colonic tissues, and nine colon cancer cell lines. Results were
      correlated with the clinicopathological features of the tumors and with the
      immunohistochemical expression of several carbohydrate tumor-associated antigens
      that may reside on mucins. MUC1 mRNA was expressed in all colonic tissues, and
      levels in paired normal and cancer tissues were similar in most cases. MUC2 and
      MUC3 mRNAs were expressed in both normal and cancer tissues, but levels were
      often decreased in the cancers. MUC4 mRNA was present in normal mucosa with
      comparable or sometimes greater expression in cancers. There was no apparent
      correlation between the expression of any particular mucin gene or pattern of
      mucin genes and the site, stage, or histological type of tumor. In addition, the
      expression of mucin-associated carbohydrate antigens did not correlate with any
      individual mucin gene or group of mucin genes. In colon cancer cell lines all
      four MUC genes were expressed rather weakly or not at all. These results indicate
      that the human colon expresses a broad repertoire of mucin genes which are
      differentially regulated in malignancy. Whether this differential regulation of
      mucin genes affect the behavior of the tumor and results in the altered
      glycosylation commonly seen in these requires further investigation.

PMID- 1394224
TI  - Differential expression of ras protooncogenes during in vitro differentiation of
      human erythroleukemia cells.
AB  - We have compared the expression of the ras protooncogene family (H-, K-, and N
      ras) in leukemia cell differentiation utilizing as a model K562 and HEL
      erythroleukemia cells treated either with 1-beta-arabinofuranosylcytosine or 12-O
      tetradecanoylphorbol-13-acetate (TPA). 1-beta-D-Arabinofuranosylcytosine induced
      terminal erythroid differentiation of K562 cells, while TPA induced myeloid
      differentiation of K562 and HEL cells, resulting in myelomonocytic-like cells
      expressing macrophagic and megakaryocytic markers. H-ras mRNA levels showed a
      dramatic decrease in K562 cells subjected to erythroid and myelomonocytic
      differentiation. The same result was found at the protein level for p21H-ras.
      Expression of K-ras and N-ras in K562 cells also decreased with differentiation,
      although significant mRNA levels remained despite cessation of cell
      proliferation. The decrease in K-ras expression was greater for TPA-treated cells
      than for 1-beta-arabinofuranosylcytosine-treated cells. TPA-induced
      myelomonocytic differentiation in HEL cells also resulted in a dramatic down
      regulation of H-ras mRNA levels. Thus, by using a leukemia cell line able to
      differentiate along two different lineages, our results reveal a lineage-specific
      modulation of ras gene family expression.

PMID- 1394225
TI  - Frequent p53 mutations in head and neck cancer.
AB  - Squamous cell carcinomas of the head and neck (SCCHN) are associated strongly
      with the use of tobacco and alcohol, but little is known about the molecular
      pathogenesis of these tumors. In the present study, we analyzed SCCHN for
      mutations in the tumor suppressor gene p53 by immunocytochemistry and
      complementary DNA sequencing. Overexpression of p53 protein was detected in 13
      (100%) of 13 SCCHN cell lines and in tumor cells cultured directly from 10 (77%)
      of 13 patients with SCCHN. Direct evidence for p53 mutations was obtained by
      sequencing p53 complementary DNA from eight SCCHN cell lines and two tumor
      xenografts. The genetic alterations included seven missense mutations resulting
      in single amino acid substitutions, a mutation encoding a stop codon, one 10-base
      pair deletion, and one 2-base pair addition. All seven missense mutations were G
      to T transversions, five of which were clustered at codons 245 and 248. A similar
      high frequency of G to T transversions predominates in lung cancer, another
      tobacco-related disease. Mutation of the p53 gene is the most common genetic
      alteration detected in SCCHN and implicates this gene locus as a critical site of
      specific damage by mutagenic carcinogens in tobacco, one of the important risk
      factors in the etiology of this disease.

PMID- 1394226
TI  - 2H-nuclear magnetic resonance imaging of tumor blood flow: spatial and temporal
      heterogeneity in a tissue-isolated mammary adenocarcinoma.
AB  - 2H-Nuclear magnetic resonance imaging of deuteron accumulation in tissue
      following an i.v. bolus of deuterium oxide provides a noninvasive means of
      constructing maps of tissue perfusion. With a measured arterial input function
      and a simple model for tissue-capillary exchange, these data can provide
      quantitative estimates of local flow. This technique was tested in rat brain and
      then applied to the study of spatial heterogeneity and temporal variation of
      blood flow in the tissue-isolated R3230AC mammary adenocarcinoma. Global flow
      from the brain averaged 0.96 ml/min.g, in good agreement with results obtained
      from other methods; the perfusion of brain was relatively homogeneous. Global
      tumor blood flow averaged 0.32 ml/min.g, ranging from 0.11 to 0.96 ml/min.g.
      Imaging revealed variations in perfusion both within and between the tumors that
      far exceeded those expected from brain flow heterogeneity and uncertainty in the
      flow estimates. By obtaining repeated flow images at 30-min intervals, it was
      possible to show that the regional blood flow shifted with time in single pixels
      and in multipixel regions. These experiments show that 2H-nuclear magnetic
      resonance may be useful in obtaining noninvasive and quantitative measurement of
      temporal blood flow changes in a solid tumor in vivo.

PMID- 1394228
TI  - Targeted therapy of athymic mice bearing GW-39 human colonic cancer
      micrometastases with 131I-labeled monoclonal antibodies.
AB  - The therapeutic potential of radiolabeled antibodies is usually evaluated in
      experimental animal models bearing s.c. xenografts. We have established a
      micrometastatic model of the GW-39 human colonic carcinoma in the nude mouse lung
      (J. Natl. Cancer Inst., 83: 627-632, 1991) and presented preliminary findings on
      the efficacy of a 131I-anticarcinoembryonic antigen (CEA) antibody in this model.
      We now extend our observations on the use of radioiodinated labeled monoclonal
      antibodies (MAbs) to treat multiple small tumor nodules. Biodistribution and
      dosimetry analysis was performed for intact and F(ab')2 of NP-4 anti-CEA IgG, Mu
      9 anti-colon-specific antigen IgG, isotype-matched irrelevant anti-AFP IgG, and
      intact MAb 34A anti-lung endothelial IgG antibody. Comparisons were made for rad
      dose delivered to small s.c. tumors, normal lung, lung with tumor nodules, and
      isolated tumor nodules. Survival curves were generated for tumor-bearing animals
      treated 1, 7, or 14 days after tumor cell implantation with these antibodies
      using the maximal tolerated dose for intact antibodies (275 microCi) and for
      F(ab')2 fragments (1.2 mCi). The studies established the following observations:
      (a) in contrast to previous results in a bulky tumor model in hamsters, intact
      antibodies are more therapeutic than MAb fragments for both NP-4 and Mu-9; (b)
      tumor nodule size, even on the microscopic level, affects therapeutic outcome;
      antibodies were more effective when administered 7 days postimplantation (mean
      nodule diameter, 150 microns) compared with treatment 14 days postimplantation
      (mean nodule diameter, 750 microns); (c) administration of radioiodinated Mu-9
      was exquisitely effective on single avascular tumor cells that had seeded in
      lung; irrelevant antibody was minimally radiotoxic; (d) as in the bulky disease
      model, the anti-colon-specific antigen p antibody delivers a higher rad dose than
      the anti-CEA antibody and is significantly more therapeutic in the
      micrometastasis model; (e) a higher affinity anti-CEA antibody (MN-14)
      recognizing the same epitope on CEA as NP-4 was equally therapeutic; (f) the use
      of MAb directed against the lung endothelium was not as therapeutic as a tumor
      associated antibody; and (g) all tumor-associated antibodies were more
      efficacious than administration of the maximal tolerated dose of 5-fluorouracil
      and leucovorin in this human tumor-xenograft model. These results provide further
      support for the use of radioimmunotherapy in the handling of minimal disease,
      probably as part of an adjuvant treatment regimen.

PMID- 1394229
TI  - Membrane peroxidative damage enhancement by the ether lipid class of
      antineoplastic agents.
AB  - The ether lipid antineoplastic agents have no known interaction with DNA, but
      rather they appear to target membranes. The primary mechanism of action is
      unknown but effects on membrane biology are documented. We have studied the
      effect of two ether lipids on membrane lipids and examined the hypothesis that
      membrane peroxidative damage may be involved in their mechanism of action. With
      the use of cells having membranes enriched in polyunsaturated fatty acids of the
      omega-3 family of fatty acids, we have demonstrated that the prototypical ether
      lipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and a thioether lipid
      analogue, 1-O-hexadecylmercapto-2-methoxymethyl-rac-glycero-3-phosphocholine ,
      increase membrane lipid peroxidation and cytotoxicity in a time- and drug
      concentration-dependent manner. The oxidative cofactors Fe2+ and ascorbic acid
      were required. The pattern of cell death did not fully correspond to the
      peroxidation, since cofactors were required for peroxidation but not
      cytotoxicity. However, the rate of decrease in cell viability after exposure to
      the drug and cofactors corresponded to the peroxidation rate. In addition, when
      L1210 cells modified with the monounsaturated fatty acid oleic acid or unmodified
      cells were used, there was no ether lipid-enhanced peroxidation, and the cells
      were significantly less sensitive to the drug, with or without cofactors. The
      lipid-soluble antioxidant vitamin E inhibited 1-O-octadecyl-2-O-methyl-rac
      glycero-3-phosphocholine peroxidation and cytotoxicity in a concentration
      dependent manner in the presence of cofactors but not consistently without them.
      Depletion of cellular glutathione content of L1210 cells using L-buthionine-(SR)
      sulfoximine resulted in 40% augmentation of cofactor-facilitated cytotoxicity of
      1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine and a borderline effect on
      peroxidation. Another ether lipid, the thio compound 1-O-hexadecylmercapto-2
      methoxymethyl-rac-glycero-3-phosphocholine , enhanced peroxidation in the
      presence of cofactors with kinetics corresponding to those of cytotoxicity. In
      the presence of ether lipid and cofactors the intensity of ascorbate free radical
      increased, consistent with oxidative stress. We conclude that the ether lipids
      stimulate membrane lipid peroxidation in a time- and drug concentration-dependent
      manner in the presence of oxidative cofactors. Even though peroxidation may not
      fully explain the cytotoxic effect of the ether lipid class of anticancer drugs,
      this observation provides further information on the nature of the membrane
      damage induced by the drugs. Since the ether lipids generate no known free
      radical intermediates directly, this suggests that membrane damage indirectly
      results in a process involving a peroxidative reaction.

PMID- 1394227
TI  - Fibrosarcoma cells transduced with the IL-6 gene exhibited reduced
      tumorigenicity, increased immunogenicity, and decreased metastatic potential.
AB  - Murine fibrosarcoma cell lines transduced with retroviral vectors containing the
      murine interleukin 6 (IL-6) gene constitutively secreted IL-6. When injected s.c.
      into normal mice these IL-6-secreting tumors exhibited reduced tumorigenicity.
      This reduced tumorigenicity was not seen in nude or irradiated mice, implicating
      a T-cell-dependent, radiosensitive host response activated by the cytokine.
      Subcutaneous IL-6-secreting tumor did not retard the growth of distant deposits
      of wild-type tumor in the same host. However, animals rejecting IL-6-secreting
      tumors exhibited resistance to later challenge with wild-type tumor. When
      injected i.v. in an experimental metastasis model the IL-6-secreting tumors
      failed to or were extremely inefficient in giving rise to pulmonary nodules; this
      was observed in both normal and immunoincompetent mice, implicating a second,
      nonimmune mechanism affecting the growth of the tumor modified to secrete IL-6.

PMID- 1394230
TI  - Identification of the cross-link between human O6-methylguanine-DNA
      methyltransferase and chloroethylnitrosourea-treated DNA.
AB  - Chloroethylnitrosoureas induce reactive O6-guanine adducts in DNA that can form
      either interstrand cross-links or a covalent complex with the DNA repair protein
      O6-methylguanine-DNA methyltransferase (MGMT). To test our hypothesis that these
      end-products are formed from the common precursor, 1-O6-ethanoguanine, we
      compared the kinetics of interstrand cross-link formation with those of decay of
      MGMT complex forming capacity. The half-lives of these processes were identical.
      Our hypothesis also predicts that the linkage between DNA and MGMT is 1-(guan-1
      yl)-2-(cystein-S-yl)ethane. This notion was tested by forming the complex with
      35S-labeled recombinant human MGMT and a chloroethylnitrosourea-treated
      oligodeoxynucleotide. After degradation by depurination and proteolytic
      digestion, the identity of the [35S]cysteine-guanine linkage was confirmed by
      comparison with the synthetic marker compound using high performance liquid
      chromatography and UV spectrometry. These results strengthen the hypothesis that
      DNA interstrand cross-links and DNA-MGMT complex both arise from the same
      precursor. The data also suggest that 1-O6-ethanoguanine is a good substrate for
      MGMT such that, under certain conditions in vivo, DNA-MGMT complex formation may
      constitute a significant secondary lesion.

PMID- 1394231
TI  - Interleukin 4 receptor expression and growth inhibition of gastric carcinoma
      cells by interleukin 4.
AB  - The expression of the interleukin 4 (IL-4) receptor (IL-4R) and effects of human
      recombinant IL-4 on human gastric carcinoma cell lines were studied. We
      demonstrated that IL-4 inhibited the growth of gastric carcinoma cells in a dose
      dependent manner (0.1-100 units/ml) in a [3H]thymidine incorporation
      proliferation assay. The gastric carcinoma cells varied in sensitivity to
      treatment with low dose IL-4. Treatment of cells with IL-4 altered the morphology
      of the cells to a "flattened" morphological shape resembling differentiation. The
      IL-4-mediated growth inhibition was significantly abrogated by neutralization of
      IL-4 with specific anti-IL-4 antibody. IL-4R expression on the cell surface was
      determined by assessing biotin-labeled IL-4 binding to cells using flow
      cytometry. IL-4R expression ranged from 5 to 85% of total cell population in the
      gastric carcinoma cell lines assessed. There was a positive correlation between
      the sensitivity to IL-4-mediated growth inhibition and IL-4R expression. By
      Northern blot analysis, we demonstrated that mRNA of IL-4R was expressed in the
      gastric carcinoma cells. Using in situ hybridization, we confirmed that IL-4R
      mRNA was expressed in the gastric carcinoma cell at the single cell level. By
      using a sensitive polymerase chain reaction technique, we demonstrated that
      gastric carcinoma cells expressed IL-4 mRNA, suggesting a possible autocrine
      loop. These studies indicate that IL-4 can significantly modulate gastric
      carcinoma cells that possess IL-4R. IL-4R on gastric carcinoma cells may be a
      potential therapeutic target site for IL-4-directed therapy.

PMID- 1394232
TI  - Magnetic resonance diffusion imaging detects structural damage in biological
      tissues upon hyperthermia.
AB  - The use of quantitative nuclear magnetic resonance (MR) imaging to investigate
      the extent and mechanism of hyperthermic damage in biological tissues has been
      studied. By using the multiple delay-multiple echo and pulsed-gradient spin echo
      MR imaging sequences, multiple frame MR images of freshly harvested rabbit
      tissues (brain, kidney, and muscle) and intact duck embryos in shells were
      obtained before and after heat treatment (45 degrees C for 30 min) using a
      clinical 1.5-Tesla whole-body superconducting MR scanner. Based on the relaxation
      and diffusion models, maps of the proton spin density, relaxation times, and
      various self-diffusion parameters of tissue water were generated from these
      multiple frame MR images. Our results indicated that the values of the diffusion
      barrier size and fractal parameter of the tissues and the self-diffusion
      coefficient of tissue water increased significantly, i.e., approached that of
      free water, after the heat treatment. In comparison, only slight changes in the
      spin density and relaxation times of the tissue water were found after the
      identical heat treatment. We concluded that the significant changes in the self
      diffusive behavior of the tissue water are due to the denaturation of
      macromolecules (e.g., protein and fiber) within the tissues at elevated
      temperatures. We further suggested that MR diffusion imaging represents a
      powerful tool to investigate the extent and mechanism of heat damage of
      biological tissues in vivo and therefore bears important potential in the
      clinical assessment of the therapeutic efficacy of hyperthermia in cancer
      therapy.

PMID- 1394233
TI  - Somatostatin receptors in human renal cell carcinomas.
AB  - The presence of somatostatin receptors was evaluated in samples of 39 surgically
      removed human renal cell carcinomas with receptor autoradiography on tumor
      sections by using iodinated [Tyr3]octreotide as the radioligand. All types,
      grades and stages of tumors were represented. Twenty-eight of 39 renal cell
      carcinomas (72%) were shown to be somatostatin receptor positive. The receptors
      were saturable, of high affinity (KD = 0.8 nM), and were specific for
      somatostatin and bioactive somatostatin analogues. No evident correlations were
      found between the status of somatostatin receptors in the tumor and the age or
      sex of the patients, the histopathological type or grade of the tumor, or the
      tumor-node-metastasis stage of the disease. However, numerous cases considered to
      be of poor prognosis were somatostatin receptor positive. No functional
      correlates for these receptors have been established, although the presence of
      somatostatin receptors in human kidneys and somatostatin effects on renal tubular
      functions in normal human volunteers have been reported. In a patient scanned in
      vivo for islet cell carcinoma with an 123I-labeled somatostatin analogue,
      bilateral renal cell carcinomas were also visualized; multiple bilateral renal
      cell carcinomas were identified on the 1- and 4-h images taken after injection of
      123I-labeled somatostatin analogue. In conclusion, the high incidence of
      somatostatin receptors in renal cell carcinomas may have diagnostic value when
      performing in vivo imaging of somatostatin receptors and it may have potential
      therapeutic implications.

PMID- 1394234
TI  - Deletions of 17p and p53 mutations in preneoplastic lesions of the lung.
AB  - Cytogenetic and p53 mutation analysis in two cases of severe dysplasia of the
      bronchial epithelium in lung cancer patients and p53 immunostaining in a third
      one are reported. The finding of both chromosomal deletions of 17p and p53
      mutation indicates that these changes may take place early in the process of lung
      carcinogenesis.

PMID- 1394235
TI  - The RCK gene associated with t(11;14) translocation is distinct from the MLL/ALL
      1 gene with t(4;11) and t(11;19) translocations.
AB  - We previously demonstrated that the 11q23 breakpoint region, designated the RCK
      locus, of the RC-K8 B-lymphoma cell line with t(11;14)(q23;q32) is centromeric to
      PBGD, while breakpoints of infantile leukemia cell lines with t(11;19)(q23;p13)
      are detectable by pulsed-field gel electrophoresis with the CD3D probe. In the
      present study, using a probe within 1.0 kilobase of the t(11;14) breakpoint, we
      isolated a partial complementary DNA clone for the putative RCK gene, which
      detects a 7.5-kilobase mRNA. Sequence analysis predicted a novel protein of 472
      amino acids which demonstrated sequence homology to a translation initiation
      factor/helicase family. We also isolated a phage clone from the CD3D/G yeast
      artificial chromosome clone (yB22B2) which detects 11- and 12-kilobase mRNAs,
      most likely for the MLL/ALL-1 gene associated t(4;11)(q21;q23) and
      t(11;19)(q23;p13) translocations. By pulsed-field gel electrophoresis after NotI
      digestion, this recombinant clone is on a 96-kilobase fragment, while RCK and
      PBGD probes are on a more telomeric 690-kilobase NotI fragment. These results,
      altogether, suggested that two different genes, RCK and MLL/ALL-1, are associated
      with 11q23 translocation of hematopoietic tumors.

PMID- 1394236
TI  - p53 mutation and protein accumulation during multistage human esophageal
      carcinogenesis.
AB  - Preinvasive lesions of squamous cell carcinoma are well defined morphologically
      and provide a model for multistage carcinogenesis. Since alterations in the p53
      tumor suppressor gene occur frequently in invasive esophageal squamous cell
      carcinoma, we examined a set of preinvasive lesions to investigate the timing of
      p53 mutation. Surgically resected tissues from nine patients with esophageal
      squamous cell carcinoma contained precursor lesions which had not yet invaded
      normal tissues. Immunohistochemistry showed high levels of p53 protein in both
      preinvasive lesions and invasive carcinomas in six cases; sequence analysis of
      all invasive tumors identified p53 missense mutations in two cases. Preinvasive
      lesions from both tumors with mutations plus one wild-type tumor were
      microdissected and sequenced. In one patient there were different mutations in
      the invasive carcinoma (codon 282, CGGarg > TGGtrp) and a preinvasive lesion
      (codon 272, GTGval > T/GTGleu/val). In a second case, an invasive carcinoma had a
      mutation in codon 175 (CGCarg > CAChis), and adjacent preinvasive lesions
      contained a wild-type sequence. A carcinoma and preinvasive lesion from the third
      case contained high levels of protein and a wild-type DNA sequence. Therefore,
      p53 mutation may precede invasion in esophageal carcinogenesis, and multifocal
      esophageal neoplasms may arise from independent clones of transformed cells. The
      timing of p53 protein accumulation is favorable for an intermediate biomarker in
      multistage esophageal carcinogenesis.

PMID- 1394237
TI  - Prognostic value of urokinase-type plasminogen activator in 671 primary breast
      cancer patients.
AB  - Urokinase-type plasminogen activator (uPA) may be responsible for the invasive
      and metastasizing capacity of tumor cells. Evidence has been presented that
      primary breast cancer patients with tumors containing high levels of uPA
      experience a worse prognosis. In the present study we have assessed uPA status in
      routinely prepared cytosols of 671 primary human breast tumors and have evaluated
      its association with disease-free and overall survival. Isotonic regression
      analysis with length of disease-free survival as an end point revealed 1.15 ng/mg
      protein as the best cutoff point to discriminate between uPA positive (32% of the
      tumors) and uPA negative. In both Cox univariate and multivariate regression
      analysis (including also patient's age, menopausal status, lymph node status, and
      the number of positive lymph nodes, tumor size, and estrogen and progesterone
      receptor status), uPA positivity was significantly associated with increased
      rates of relapse and death. Corrected for all relevant factors in multivariate
      analyses for subgroups of patients, uPA positivity was significantly associated
      with an increased relapse rate in the subgroups of node-negative (P = 0.002;
      relative failure rate, 2.33), node-positive (P < 0.0001; relative failure rate,
      1.95), postmenopausal (P < 0.0001; relative failure rate, 2.59), and steroid
      receptor-positive patients (P < 0.0001, relative failure rate, 2.76). We conclude
      that uPA positivity of human primary breast tumors is an important independent
      variable for the identification of patients at high risk for recurrence, also in
      clinically important subgroups of patients.

PMID- 1394239
TI  - p53 mutations in formaldehyde-induced nasal squamous cell carcinomas in rats.
AB  - Formaldehyde induces squamous cell carcinomas in the nasal passages of rats
      following chronic inhalation exposure at concentrations of > or = 10 ppm. We have
      examined the complementary DNA of the tumor suppressor gene p53 from 11 primary
      formaldehyde-induced tumors for mutation using DNA sequence analysis. A
      polymerase chain reaction-amplified fragment of the rat p53 complementary DNA
      containing the evolutionarily conserved regions II-V was directly sequenced from
      each tumor. Point mutations in the p53 complementary DNA sequence were found in 5
      of 11 of the tumors analyzed. These data demonstrate p53 point mutations in
      formaldehyde-induced squamous cell carcinomas and indicate a common alteration in
      certain rat and human squamous cell carcinomas of the respiratory tract.

PMID- 1394238
TI  - Immunogenetic influences on the initiation stage of the cutaneous chemical
      carcinogenesis pathway.
AB  - While it is generally agreed that environmental exposure to solar radiation and
      to certain classes of chemicals are the major causes of nonmelanoma skin cancer,
      it is also believed that genetic polymorphisms regulating immunological responses
      are important determinants of individual susceptibility to skin cancer. However,
      little is known about their interactions with the chemical carcinogenesis pathway
      prior to the actual development of tumors. This issue was examined by comparing
      susceptibility to skin cancer in C3H/HeN and C3H/HeJ mice, two strains that
      differ only at the lipopolysaccharide genetic locus, which serves as a regulator
      of a number of immunological activities. When subjected to a two-stage cutaneous
      tumorigenesis protocol, C3H/HeJ mice, which have a mutation at the
      lipopolysaccharide genetic locus that renders them deficient in their capacity to
      produce cytokines and to activate macrophages, developed nearly three times as
      many tumors as did C3H/HeN mice, which do not have this mutation. Epidermal DNA
      binding of 7,12-[3H]dimethylbenz(alpha)anthracene, an index of tumor initiation,
      was also significantly greater in C3H/HeJ than in C3H/HeN mice. Immunological
      activities regulated by the lipopolysaccharide genetic locus thus confer
      resistance to DMBA-induced cutaneous tumorigenesis in mice and are associated
      with changes that occur early in the tumorigenesis pathway, prior to the
      development of tumors.

PMID- 1394240
TI  - The role of cytokines in the regulation of cell function and in the pathogenesis
      of disease: a Pathology A/Pathology B Study Section Workshop. Working report from
      the Division of Research Grants, National Institutes of Health.

PMID- 1394241
TI  - Chemotherapy of malignant brain tumors in children.
AB  - Chemotherapy has become an important modality in the management of children with
      brain tumors. Factors that impede improved effectiveness of anti-neoplastic drugs
      are being identified and addressed. Specific agents have emerged that show anti
      brain tumor activity alone or in combination therapy. Use of these agents
      requires facility regarding their dosing, routes of delivery, mechanisms of
      action, metabolism and toxicities. Multi-institution cooperative group trials
      provide the optimum means by which to evaluate the effectiveness of chemotherapy
      in children with brain tumors.

PMID- 1394242
TI  - The neurobiology of the opsoclonus-myoclonus syndrome.
AB  - Opsoclonus-myoclonus is a pervasive neurological syndrome of children and adults.
      Although rare, it raises important clinical and neurobiological issues. This
      article provides an overview of the clinical and laboratory features,
      differential diagnosis, treatment, and outcome of opsoclonus-myoclonus. It
      pursues immunologic, genetic, electrophysiologic, neurochemical, and other clues
      to a pharmacologic model. Key questions include how and where the brain is
      injured, reversibility of the injury, possible targets for pharmacologic
      intervention, and which new studies are needed.

PMID- 1394243
TI  - Effect of a macrolide (spiramycin) on the pharmacokinetics of L-dopa and
      carbidopa in healthy volunteers.
AB  - In one well-equilibrated parkinsonian patient treated with combined L-dopa and
      carbidopa (Sinemet), we have observed changes in treatment efficacy while
      receiving spiramycin (Rovamycine) for an intercurrent respiratory infection. A
      preliminary study of the pharmacokinetics of L-dopa and its main metabolites 3-O
      methyldopa (3-OMD) and dihydroxyphenylacetic acid (dopac) in two parkinsonian
      patients treated with Sinemet has revealed a marked decrease in the AUC0-360 of
      these two metabolites after a 3-day course of Rovamycine. In order to confirm
      this interaction, we have studied the modifications of the pharmacokinetics of L
      dopa, 3-OMD, dopac, and carbidopa in eight male healthy volunteers after a single
      dose of Sinemet 250 (L-dopa, 250 mg and carbidopa, 25 mg) before and after a 3
      day course of Rovamycine. Our study confirms this interaction. After spiramycin,
      we observed a marked reduction in AUC0-360 for L-dopa (p less than 0.001), 3-OMD
      (p less than 0.001), and carbidopa (p less than 0.001), and an increase in AUC0
      360 for dopac (p less than 0.01). The L-dopa elimination half-life was increased
      (p less than 0.012); differences in peak plasma concentrations did not attain
      statistical significance. We think that these modifications in L-dopa
      pharmacokinetics after spiramycin are due to nonabsorption of carbidopa secondary
      to modified gastrointestinal motility.

PMID- 1394244
TI  - Hypotensive and bradycardiac responses to thyrotropin-releasing hormone in a
      comatose patient.
AB  - A 46-year-old female motorcyclist, who suffered injuries to the brain stem in a
      traffic accident, showed hypotensive and bradycardiac responses to thyrotropin
      releasing hormone (TRH) given to counter consciousness disturbance. The
      cardiodepressive responses to TRH were reduced with i.v. pretreatment with
      atropine sulfate, suggesting an involvement of the vagal nervous system in the
      development of the responses. Furthermore, this patient had complicated
      impairments in the sympathetic nervous system, which were revealed by the results
      of testing baroreceptor reflex sensitivity to pharmacological alterations in
      blood pressure. We thus speculate that the hypotensive and bradycardiac effects
      of TRH observed in this patient may result from derangements of the sympathetic
      nervous system caused by the injuries. This case report is believed to be a novel
      description of the cardiodepressive effects of TRH.

PMID- 1394245
TI  - Cerebral amyloid angiopathy with granulomatous angiitis ameliorated by steroid
      cytoxan treatment.
AB  - We report a case of a 62-year-old black woman who, 8 months prior to death,
      developed confusion, apraxias, disorientation, and difficulties with her vision.
      There was no dementia. Computed tomography (CT) scan and magnetic resonance
      imaging (MRI) suggested a tumor in the right posterior parietal white matter. A
      biopsy of the lesion displayed granulomatous angiitis and severe cerebrovascular
      amyloidosis, but no tumor was identified. Chronic inflammation with an occasional
      multinucleated giant cell was seen about the amyloid-infiltrated vessels. The
      cortex demonstrated gliosis but no plaques or tangles. Subsequently, the patient
      was treated with steroids and Cytoxan, with an improvement in her neurologic
      status. She died of opportunistic bronchopneumonia 8 months after the initial
      onset of her symptoms. On postmortem examination, the biopsied area of the brain
      showed atrophy with gliosis. Amyloid angiopathy was present but in much lesser
      degree than in the biopsy. Scant perivascular inflammatory infiltrates were seen
      only focally, and no giant cells were observed. The amyloid, both in the biopsy
      and autopsy material, was of the Alzheimer A4 type. This case suggests that
      steroid and cytoxan treatment ameliorated the angiitis and the amyloid angiopathy
      as well. The pertinent literature is discussed.

PMID- 1394246
TI  - Primary aqueduct stenosis as a cause of hydrocephalus.

PMID- 1394247
TI  - Ultrasonography in the management of hydrocephalus.

PMID- 1394248
TI  - Electrical stimulation and multichannel EMG recording for identification of
      functional neural tissue during cauda equina surgery.
AB  - Electrical stimulation of structures within the surgical field was used to
      identify functional neural elements during 25 cauda equina operations. EMG
      responses from anterior thigh, posterior thigh, and anal sphincter muscles were
      recorded simultaneously using a multichannel signal averager. During nine
      operations, stimulation of a presumed filum terminale or other tissue produced
      clear EMG responses, prompting modification of surgical procedures. In one
      patient, this resulted in preservation of a flattened spinal cord which resembled
      a band of scar tissue. Some EMG responses were restricted to a single muscle
      group; these neural structures would probably not have been identified if only a
      single-channel EMG recording was used. Visual examination alone was not adequate
      for identifying functional neural elements, or for determining whether atretic
      appearing nerve roots were functional. Electrical stimulation with multichannel
      EMG recording facilitates the preservation of functional neural elements and the
      optimization of surgical results in cauda equina surgery.

PMID- 1394249
TI  - Neurological outcome following neonatal post-haemorrhagic hydrocephalus: the
      effects of maximum raised intracranial pressure and ventriculo-peritoneal
      shunting.
AB  - The neuromotor outcome of 33 survivors of grade 3 or 4 neonatal post-haemorrhagic
      hydrocephalus born between 1975 and 1988 was assessed at a mean age of 4.7 years
      (9 months to 13 years). Two outcomes were determined: 12 patients were either
      normal (10 or had neurological signs without functional impairments (2), while
      21/33 were moderately (16), severely (2), or profoundly impaired (3).
      Intracranial pressure (ICP) was measured in 26/33 patients (4-40 mm Hg): 2 had
      normal pressures (< 5.6 mm Hg) and were normal. Raised ICP was not significantly
      different between outcome groups. Twenty-seven children were shunted; 10/27 had
      five or more operations (up to 14) and all of these had abnormal neurological
      outcomes, whereas the number of children with 1-4 shunt procedures was equal in
      both outcome groups. The rise in morbidity after the fourth shunt procedure may
      be associated with the ventriculitis suffered by 9 of the 10 patients with more
      than four shunts (P < 0.01): this compares with 4/14 cases of ventriculitis in
      the children with 2-4 shunts and no cases of infection in the 3/27 who were
      shunted once. Outcome was independent of antenatal and perinatal factors
      including the age at or mode of presentation, and was unrelated to grade of
      intraventricular haemorrhage or parenchymal changes on ultrasound or CT scanning.
      CONCLUSION: for these small numbers, adverse outcome is statistically related to
      more than four shunt procedures and ventriculitis but independent of maximum ICP
      or other perinatal factors.

PMID- 1394250
TI  - Surgical management of posthemorrhagic hydrocephalus in 22 low-birth-weight
      infants.
AB  - In order to assess the complication rates of cerebrospinal fluid diversion
      techniques used at our institution, a retrospective study of the surgical
      management of posthemorrhagic hydrocephalus was conducted from a population of
      547 premature infants admitted to the neonatal intensive care unit from 1987 to
      1989. The incidences of periventricular-intraventricular hemorrhage in the 3
      years studied were 44%, 37%, and 27%, respectively. Thirty-nine of the infants
      developed posthemorrhagic hydrocephalus as determined by serial cranial
      ultrasonography; 22 required cerebrospinal fluid diversion. During the study
      period, we began using subcutaneous ventricular reservoirs and a low-pressure
      Neonatal Shunt (customized device) in infants weighing less than 1500 g at the
      time of instrumentation. This change in management was associated with a
      significant reduction (P < 0.005) in the morbidity and mortality compared to the
      use of external ventricular drainage devices. On the basis of these findings, the
      use of external ventricular drainage devices was discontinued.

PMID- 1394251
TI  - Congenital arachnoid cyst of the lateral ventricles in children.
AB  - The authors report a series of three children with symptomatic congenital
      arachnoid cyst of the lateral ventricles. Presenting symptoms consisted of
      macrocephally, delay in psychomotor development, and seizures. CT findings were
      of a well-defined cystic lesion placed in the atrium of the lateral ventricle.
      One child was treated by direct cyst exposure and cysto-peritoneal shunt. The
      other two were treated with ventriculo-cysto-peritoneal shunts; in one of these,
      we used a ventriculoscope both for cyst fenestration and for accurate shunt
      placement. The origin of intraventricular arachnoid cysts seems to be secondary
      to the displacement of arachnoid cells by the vascular mesenchyma, through the
      choroid fissure, during the process of choroid plexus development.

PMID- 1394252
TI  - Pseudotumor syndrome in treated arachnoid cysts.
AB  - We report three patients with arachnoid cysts treated by cyst-peritoneal shunting
      in whom intracranial hypertension occurred during episodes of shunt malfunction.
      In one case this was associated with re-expansion of the arachnoid cyst, whilst
      in the other two cases this did not occur. The similarities between these two
      cases and patients with pseudotumor cerebri suggest a common pathogenic mechanism
      -specifically, a disturbance of the cerebrospinal fluid circulation.

PMID- 1394253
TI  - Description of two informative cases of occult spinal dysraphism with remarks on
      possible traits in the embryogenesis.
AB  - Two cases of spinal occult dysraphism are described. The association of a dermoid
      cyst and ectopic tissue foci of both ecto- and mesodermal origin at the junction
      zone between lipoma and nervous tissue is argued to support the disjunction
      theory on lipomeningomyelocele formation.

PMID- 1394254
TI  - Hyperfractionated radiotherapy and polychemotherapy in brain stem tumors in
      children.
AB  - Between October 1989 and January 1991 five children with brain stem tumors were
      treated with sequential chemo- and radiotherapy. The polychemotherapy consisted
      of procarbazine, ifosfamide, etoposide, methotrexate, cisplatin and cytosine
      arabinoside. Locally, hyperfractionated radiotherapy was delivered at a total
      dose of 63.8 Gy (1.1 Gy twice daily, 10 fractions per week). After a median
      observation time of 11.8 (range 4-23) months from diagnosis three children are
      alive and without evidence of tumor progression. Two patients died from tumor
      progression 11 and 16 months respectively after initiation of therapy.

PMID- 1394255
TI  - Single photon emission computerized tomography in childhood hydrocephalus.
AB  - Single photon emission computerized tomography (SPECT) is now widely used as one
      of the tools in evaluating cerebral blood flow (CBF). The authors report the CBF
      changes in childhood hydrocephalus. Five pediatric cases studied by 123I-IM SPECT
      in children are presented. The authors counted radioactivities both in early and
      delayed images in each patient, and calculated the reabsorption ratio (RR). Two
      negative-RR cases and three positive-RR cases were found. All of the negative-RR
      patients had a poor prognosis, while all of the positive-RR patients had a
      favorable outcome.

PMID- 1394256
TI  - Occurrence and management of fractured peripheral catheters in CSF shunts.
AB  - A series of 716 children underwent 2065 cerebrospinal fluid shunt procedures.
      Shunt failure due to fracture of the peripheral drain occurred 60 times, 38 times
      in ventriculo-atrial and 22 times in ventriculo-peritoneal shunts. The break
      occurred most commonly 2-4 cm above the neck incision in cardiac and just
      cephalad to the clavicle in abdominal drains. Fifty-nine ruptures occurred in
      Pudenz catheters (which were used in 82% of the shunts) and 1 occurred in a
      Holter drain (used in 17%). The fractured atrial catheters remained in situ
      (5/38) or were dislodged into the right cardiac ventricle (14/38), pulmonary
      arteries (9/38), right atrium (5/38) or hepatic veins (3/38). Two of the ruptured
      drains could not be located. Removal by a percutaneous transvascular snare
      technique was attempted in 27 cases and was successful in 24.

PMID- 1394257
TI  - Laminotomy: a technical note.
AB  - In order to restore spinal integrity following posterior exposures of the spinal
      canal in children, we describe modifications of Raimondi's laminotomy technique.
      The use of a pneumatic dissecting tool with foot-plate to create a hinged
      osteoplastic laminotomy is described, as are techniques for securing the
      laminotomy flap in place at the end of the procedure.

PMID- 1394258
TI  - Repair of giant occipital encephaloceles with microcephaly secondary to massive
      brain herniation.
AB  - Giant occipital encephaloceles rarely contain large amounts of neural tissue that
      cannot be replaced in the abnormally small calvarium. Resection of neural
      elements is therefore often necessary in order to accomplish a closure. A
      technique is described wherein an extracranial compartment is prepared utilizing
      fine tantalum mesh to enclose the neural contents. The mesh is attached to the
      periphery of the skull defect providing a rigid extracranial compartment for the
      encephalocele. As intracranial pressure increases, the calvarium is forced to
      expand. The tantalum mesh is gradually imbricated into the calvarium by daily
      digital compression. If ventriculomegaly occurs, an interval ventriculoperitoneal
      shunt is placed. The encephalocele repair is reopened and the tantalum is
      surgically imbricated at that time. This allows for a satisfactory cosmetic
      result with preservation of all neural elements.

PMID- 1394259
TI  - Abnormal cerebral hemodynamics during attacks of alternating hemiplegia.
AB  - Frequent episodes of bilateral weakness and apathy, followed later by hemiplegia
      of alternating sides were observed in a now 32-month-old girl. Transcranial
      Doppler ultrasonography showed reduced flow velocities in the middle cerebral
      artery of the affected side during a hemiplegic attack and increased flow
      velocities at different sites of the basilar artery during a bilateral episode.
      These abnormal cerebral hemodynamics appear to indicate that alternating
      hemiplegia and some forms of migraine have a similar pathophysiology.

PMID- 1394260
TI  - Traumatic cervical syringomyelia related to birth injury.
AB  - A rare case of cervical syringomyelia related to breech delivery is reported. The
      initial diagnosis was bilateral brachial plexus palsy due to birth injury, which
      was revealed by magnetic resonance imaging (MRI) to be traumatic syringomyelia.
      The usefulness of MRI in the early diagnosis of cervical cord birth injury,
      especially in differentiating between brachial plexus palsy due to birth injury
      and spinal cord trauma due to birth injury in infancy, is emphasized.

PMID- 1394261
TI  - Muscle phosphofructokinase deficiency in a myopathic child with severe mental
      retardation and aplasia of cerebellar vermis.
AB  - Muscle phosphofructokinase (PFK) deficiency in man is responsible for at least
      two forms of myopathy; one is characterized by painful contractures of muscles
      and typically occurs in adults, whereas the other is often disabling and
      typically occurs in childhood, with psychomotor and growth retardation. In this
      investigation, a young myopathic patient with severe mental retardation and
      aplasia of the cerebellar vermis presented with muscular hypotrophy of the limbs,
      generalized hypotonia, convergent strabismus and marked pain during passive
      movement. Biopsy of quadriceps femoris muscle showed variation in the fiber size
      with sarcoplasmic areas positive for periodic acid-Schiff stain. Histochemical
      qualitative reaction for PFK showed no staining of muscle fibers; ultrastructural
      studies showed abnormal accumulation of glycogen granules in both
      intermyofibrillar and subsarcolemmal areas. While some enzyme activities in the
      muscular crude extract were significantly lower than in controls, direct assay of
      PFK revealed no activity, thus demonstrating that the child's myopathy was due to
      the lack of PFK activity.

PMID- 1394262
TI  - Catecholamine alterations in experimental hydrocephalus.
AB  - Experimental hydrocephalus was induced in rats by intracisternal injection of
      kaolin suspension. The amounts of norepinephrine and dopamine were determined in
      the whole brain and specific brain regions at 1 week (acute phase) and 4 weeks
      (chronic phase). The turnover of catecholamine, an index of the activity of
      catecholamine-containing neurons, was determined by measuring the decrease in
      catecholamine contents 2 h after intraperitoneal injection of alpha-methyl-p
      tyrosine (250 mg/kg), an inhibitor of tyrosine hydroxylase. We observed that the
      catecholamine contents in kaolin-induced hydrocephalus were not significantly
      different from control values. Following injection of alpha-methyl-p-tyrosine,
      there was decrease in levels of catecholamines in both control and hydrocephalic
      rats. This decrease was, however, significantly less in induced hydrocephalus
      than in control animals. This result suggested that in hydrocephalus, the
      activities of norepinephrinergic and dopaminergic neurons are reduced.

PMID- 1394263
TI  - The child with a mass on its head: diagnostic and surgical strategies.
AB  - A series of 65 pediatric patients with scalp or calvarial masses is reported on.
      The majority of children presented with a disfiguring or painful mass on the
      head. Clinical findings suggested the correct diagnosis in 39/65 cases, skull
      radiographs in 46/65, and CT in 49/65. Taking the combined results of clinical
      and radiological studies, 54/65 of the lesions were accurately diagnosed. Tumor
      excision was curative in 43 of 48 patients who were operated on. Most scalp and
      calvarial neoplasms were benign; only 5/65 children harboured a malignant lesion.
      There was no mortality related to surgery in the series. Surgical intervention
      seems to be indicated in most cases, both for diagnosis and for treatment.

PMID- 1394264
TI  - Gangliogliomas in childhood.
AB  - Ganglioglioma is a tumour of the central nervous system composed of an admixture
      of dysplastic nerve cells resembling pleomorphic ganglion cells, and glial
      elements, which may be astrocytic and/or oligodendroglial in appearance. A series
      of 12 patients aged between 9 months and 15 years 9 months, all of whom had
      suffered epilepsy refractory to medical treatment for up to 8 years, is
      presented. Computed tomographic and magnetic resonance scans were of prime use in
      localisation of the tumours. Calcification was noted preoperatively in 4 of 12
      cases. The majority of patients obtained at least partial relief from symptoms
      after complete or partial resection. Histologically, 11 of the tumours included
      grade 1 astrocytic elements and the remaining one exhibited grade 2 areas. The
      diagnosis of ganglioglioma should be suspected in a child with refractory, long
      standing epilepsy. Prognosis of these tumours is determined by the astrocytic
      component; if this is of low grade, surgical excision may result in marked
      symptomatic improvement or cure.

PMID- 1394265
TI  - Attempts to induce immune-mediated cerebral arterial injury for an experimental
      model of moyamoya disease.
AB  - To examine the possible role of immune complex-mediated reactions in moyamoya
      disease, a novel experimental system using a serum sickness vasculitis model
      combined with intracisternal administration of antibodies or antigens was
      developed. Twenty-eight male Japanese white rabbits were divided into four
      experimental groups. Group I was treated twice with intravenous injections of
      heterologous serum. In group II, intracisternal administration of antibodies or
      antigens was combined with the second injection of serum. Group III received a
      single intravenous injection of antigens simultaneously with intracisternal
      administration of antibodies. Group IV was a technical control group. Cerebral
      arteritis, although likely in the initial process, was induced only in groups II
      and III. This study suggests that the cerebral arteries rarely develop arteritis
      in a serum sickness model alone. The cerebral arteries may require additional
      intracisternal administration of antibodies or antigens to induce in situ
      deposition of immune complexes around them.

PMID- 1394266
TI  - Predicting the recurrence of ependymomas from the bromodeoxyuridine labeling
      index.
AB  - The usefulness of histopathological grading in predicting the prognosis of
      patients with ependymomas is controversial. To clarify the discrepancy between
      the histological malignancy and the prognosis of these tumors, we estimated the
      proliferative potential of 32 intracranial and intraspinal ependymomas and
      correlated the findings with the clinical behavior. Each patient received an
      intraoperative infusion of bromodeoxyuridine (BUdR, 200 mg/m2 i.v.) before tumor
      removal; the BUdR labeling index (LI), or percentage of BUdR-labeled cells, was
      determined immunohistochemically in excised specimens. The mean BUdR LI (+/- SD)
      of intracranial malignant ependymomas was 4.1 +/- 2.8%. Nonmalignant intracranial
      and intraspinal ependymomas and subependymomas had mean LIs of 1.5 +/- 0.9%, 1.1
      +/- 0.3%, and less than 1%, respectively. Overall, 44% of the tumors recurred.
      There were no statistically significant differences in the recurrence rates of
      intracranial and intraspinal ependymomas, including subependymomas (43% and 44%,
      respectively), or of intracranial ependymomas with LIs greater than 1.0% and less
      than 1.0% (67% and 44%, respectively). However, the early recurrence rate (within
      24 months after treatment) of tumors with LIs greater than 1.0% was higher than
      that of tumors with LIs of less than 1.0% (100% vs. 25%, P less than 0.05). The
      BUdR LI also showed a statistically significant inverse correlation with the time
      to recurrence. These findings indicate that BUdR LI reflects the proliferative
      potential of individual ependymomas and can be used to help predict the
      recurrence and estimate the prognosis of these tumors.

PMID- 1394267
TI  - Brain abscess in infants.
AB  - Brain abscesses are rare in infants and their clinical presentation is specific
      for this age group. Seven cases of brain abscess in infants aged 2-11 months are
      reported. The underlying cause was meningitis in four, sepsis in two, and unknown
      in one. Gram-negative organisms were cultured in 6 patients. The abscess size was
      5 cm or more in five cases; in four there were multiple lesions. Two abscesses
      were aspirated and irrigated; four particularly large lesions were drained and
      repeatedly aspirated and irrigated. One craniotomy was done. There were two
      deaths, one in the postoperative period and the other 6 months after discharge.
      Follow-up information is available for four children, showing a good result in
      only one of them. Formation of an abscess should be diagnosed early, and close
      ultrasound monitoring or CT scanning in infants with bacterial meningitis and
      sepsis is essential. The prognosis in cases in which large/multiple abscesses
      develop is poor.

PMID- 1394269
TI  - Scalp aplasia cutis congenita: closure by the L-shaped flap.
AB  - A case of aplasia cutis congenita of the scalp with bony defect in a newborn
      treated by early excision and reconstruction is presented. A recently described
      versatile minor flap is employed to cover the resultant defect. The advantages of
      early surgical repair and the flap are highlighted.

PMID- 1394270
TI  - A system of halo brain retraction without skull fixation.

PMID- 1394268
TI  - Arachnoid cysts in children: a European co-operative study.
AB  - The data on arachnoid cysts in children (0-15 years) operated upon between 1980
      and 1988 were analysed in a retrospective, co-operative study. The results from
      285 patients indicate a predominance of these lesions in boys (64%) more than
      girls (36%) and a mean age of 6 years at onset of symptoms. Focal EEG patterns
      corresponding to the cyst's location were encountered in 32%. About 40% of all
      cysts were located along the midline, the sylvian fissure representing the
      predominant location. Open surgery, i.e. total excision or marsurpialization
      (together 43.3%), emerged as the first-choice surgical procedure. The type of
      surgery switched somewhat to shunting procedures in cases of lesions in deeper
      locations (22.8%). Morphological results on follow-up revealed a reduction of the
      size of the cyst in a significant majority (61%); in 18% the cyst had disappeared
      completely on CT scans. There was an obvious correlation between postoperative
      morphological findings and clinical outcome.

PMID- 1394271
TI  - Intramedullary spinal cord abscess: a case report.
AB  - An 11-year-old boy presented with pain in the back, urinary retention, paraplegia
      and loss of sensations below L1. Investigations revealed an intramedullary
      lesion. An intramedullary spinal cord abscess was found at surgery. The pus was
      evacuated and abscess was excised. Minimal recovery was seen following surgery.
      Early intervention and a high index of suspicion is required in such cases.

PMID- 1394272
TI  - Periventricular hydatid cyst presenting with hemichorea.
AB  - A case of periventricular hydatid cyst presenting with only hemichorea is
      reported. The unusual clinical course is described.

PMID- 1394273
TI  - Ascaris lumbricoides: an unusual cause of shunt infection.
AB  - Two cases of delayed shunt infection attributable to the abdominal complications
      of Ascaris lumbricoides infestation are reported. The first child presented with
      a peritoneal shunt catheter protruding through the anus and the second patient
      was found to have two live worms around the cephalic shunt tubing. Both had
      enteric shunt infections which responded well to therapy. The epidemiology and
      treatment of ascariasis are briefly discussed.

PMID- 1394274
TI  - Orbital porencephalic cyst following penetrating orbitocranial trauma.
AB  - In a 10-year-old boy an orbitocranial penetrating wound produced by an umbrella
      tip caused an orbital roof bone fragment to penetrate up to the anterior part of
      the third ventricle behind the left foramen of Monro. Hemorrhages and
      encephalomalacia developed along the trajectory of the fragment and subsequently
      a porencephalic cyst was formed at this site. Six months after the trauma,
      increased pressure developed in the left ventricular system due to obstructive
      hydrocephalus and consequently the porencephalic cyst herniated into the orbit
      through the orbital roof fracture, producing intermittent diplopia, left
      exophthalmos, and palpebral swelling. A ventriculo-peritoneal shunt led to
      shrinkage of the orbital cyst content and resolution of the symptoms.

PMID- 1394275
TI  - Classification of the cerebral edemas with reference to hydrocephalus and
      pseudotumor cerebri.
AB  - Cerebral edema is a common clinical disorder that results from an abnormal
      increase in water content within the extracellular (EC) compartment of the brain.
      It is distinguished from two other types of brain bulk enlargement: (1) vascular
      swelling, caused by arterial dilatation or venous obstruction; and (2) cellular
      swelling, caused by cytotoxic injuries or metabolic storage. Under normal
      conditions, the EC compartment has two fluids, the interstitial fluid (ISF) and
      the cerebrospinal fluid (CSF), and extends from the blood brain barrier (BBB)
      through a series of 100 to 150-A-wide intercellular spaces that are anatomically
      continuous with the CSF spaces. There are four primary types of EC edema: (1)
      vasogenic edema, which results from an increase in brain capillary permeability,
      the most common type, in which leakage of plasma constituents into the brain
      follows the pathways of ISF bulk flow and is governed by the interaction of
      systemic arterial pressure and tissue resistance; (2) osmotic edema, which
      results from an unfavorable osmotic gradient between the plasma and ISF across an
      intact BBB; (3) compressive edema, which results from obstruction of ISF bulk
      flow pathways; and (4) hydrocephalic edema, which results from obstruction of CSF
      bulk flow pathways. In this latter type of edema, distension of the collecting
      channels proximal to the block leads to retrograde flooding of the EC compartment
      with the formation of periventricular edema. The syndrome of pseudotumor cerebri
      includes several different types of brain bulk enlargement.

PMID- 1394276
TI  - Occlusion of the sagittal sinus in craniectomized rabbits.
AB  - Most attempts at production of hydrocephalus in experimental animals by
      obstructing the venous sinuses have failed. In adult humans, venous sinus
      occlusion usually results in the clinical syndrome of pseudotumor cerebri with
      small or normal sized ventricles. However, in children less than 18 month old
      with venous sinus hypertension, ventriculomegaly has been reported. We examined
      the change in ventricular size in craniectomized animals (simulating children
      with open sutures) with occlusion of the superior sagittal sinus. New Zealand
      rabbits weighing 1500-1800 g were anesthetized with an intramuscular injection of
      2 ml 7:3 ketamine (100 mg/ml): Rompun (xylazine) (20 mg/ml) solution. The scalp
      was shaved, prepped with Betadine, and infiltrated with 1% lidocaine, and a
      midline scalp incision made. The periosteum was reflected laterally and a
      craniectomy performed with microscopic magnification. The dura was exposed
      overlying both cerebral hemispheres and the superior sagittal sinus from its
      origin to the torcular. In five control animals, the scalp was then closed. In
      ten experimental animals, small incisions were made in the dura just lateral to
      the superior sagittal sinus with a no. 11 scalpel and then with microscopic
      magnification the sinus was coagulated with bipolar cautery and transected; the
      scalp was then closed. All animals were allowed 5-7 days to recover, then
      ultrasound was used to assess ventricular size. We observed a small but
      statistically significant increase in ventricular size in the experimental group
      compared to the control group. This model provides evidence that venous sinus
      occlusion in animals with expandable crania can produce ventriculomegaly.

PMID- 1394277
TI  - Pathogenesis of diastematomyelia: can a surgical model in the chick embryo give
      some clues about the human malformation?
AB  - To reproduce diastematomyelia, a sagittal incision was carried out at the level
      of the rhomboidal sinus of 36- to 40-h-old chick embryos. A small piece of
      membrane shell, a small agar screen, or a piece of quail isochronous isotopic
      notochord was inserted into the gap. The embryos were killed and fixed after 9
      days' incubation. Diastematomyelia was obtained in several embryos treated with
      interposition of a membrane screen or a piece of quail notochord. Microscopic
      examination revealed two hemicords, each containing its own central canal; in
      some cases one of the cords showed hydromyelia. Absence of the rump was seen in
      association with experimental diastematomyelia. The interposition of a resorbable
      agar screen did not succeed in reproducing diastematomyelia. The results of these
      surgical manipulations suggest that diastematomyelia cannot be explained by a
      primary disorder of neurulation. It supports the theory of noninvolution of a
      firm midline structure (probably the neurenteric canal, rapidly surrounded by
      mesodermal cells originating from the notochord), which prevents the fusion of
      the separated parts.

PMID- 1394278
TI  - Retroflexion of holoprosencephaly: report of two cases.
AB  - Two cases of retroflexed holoprosencephaly are presented. Reports of nine cases
      of retroflexion were available in the literature. Case analysis indicates that
      retroflexion results from subdural fluid collection. The incidence of
      retroflexion in holoprosencephaly was apparently higher than that of ordinary
      subdural hygromas. Possible explanations for this high incidence are given. The
      clinical significance and management of retroflexion are touched upon.

PMID- 1394279
TI  - Klippel-Feil syndrome revisited: diagnostic pitfalls impacting neurosurgical
      management.
AB  - Klippel-Feil syndrome in its most basic definition includes several anomalous
      conditions of the cervicomedullary junction and suboccipital region. Pediatric
      neurosurgeons are often involved in surgical palliation of this syndrome, without
      realizing how the accompanying anomalies may obfuscate management in the older
      child. A brief review of the embryology of the rhombencephalon helps to clarify
      the etiology of some of these symptoms which may cause confusion and,
      occasionally, inappropriate treatment. Illustrative cases will demonstrate some
      of these pitfalls. Appropriate early intervention, such as posterior fossa
      decompression, ventricular shunting, and fundal plication, may help to avoid
      needless morbidity. The advent of magnetic resonance scanning has helped to
      clarify the diagnosis and resulted in more appropriate treatment in these cases.

PMID- 1394280
TI  - Controversy pertaining to therapeutic modalities for tumors of the pineal region:
      a worldwide survey of different patient populations.
AB  - The management of tumors of the pineal region differs between Western countries
      and Japan. This paper reports on a worldwide survey of individual experience and
      regimens for treating pineal region tumors in different patient populations.
      Fifteen pediatric neurosurgeons from nine different countries participated in the
      survey, and a total of 408 pineal region tumors were evaluated. Determination of
      tumor histology as an initial procedure was strongly supported by the majority of
      neurosurgeons in North and Central America and Europe (group A), whereas all but
      one from Asia and Egypt (group B) emphasized initial application of the radiation
      test. The analysis of patient populations clearly revealed racial differences in
      tumor type which explain this discrepancy. Germinoma, the most radiosensitive
      tumor, constituted 43-70% (mean: 53.7%) of tumors in group B, followed by
      teratoma, pineoblastoma, and others, whereas in group A the incidence of
      germinoma was only 21-44% (mean: 34.7%), followed by a variety of tumors, such as
      astrocytoma, pineoblastoma, etc. The age distribution among intracranial germ
      cell tumors (GCT) obtained from data from the Brain Tumor Registry in Japan also
      demonstrated clear differences in the incidence of tumor types in different age
      groups in Japan: while germinoma constituted 70-84% of GCT in patients between
      the ages of 15 and 35 years, the incidence was much lower before 15 years and
      after 35 years, being 24% of tumors under 4 years and 34% of tumors after 40
      years of age. The therapeutic regimen for pineal region tumors should depend on
      the patient population concerned, because of the differences relating to race and
      age distribution.

PMID- 1394282
TI  - Acute spontaneous subdural hematoma in a teenager.
AB  - A teenager with a history of sudden onset of headache and vomiting is described.
      Computed tomography revealed an acute subdural hematoma in the right
      temporoparietal region, causing marked compression of the right ventricular
      system and a shift of midline structures to the left. No operation was carried
      out because the symptoms and neurological signs were slight enough to allow
      monitoring by means of close clinical and neuroradiological investigations.
      Within 18 days the hematoma resolved spontaneously and completely. There was no
      history of trauma or any objective sign of trauma about the face or head, and
      radiography of the skull showed no fracture. We are not aware of any other report
      of a spontaneous subdural hematoma which did not require surgery. This feature
      makes our case unique. In addition, comparable cases in the literature are
      reviewed and the etiological possibilities of spontaneous subdural hematoma are
      discussed.

PMID- 1394281
TI  - A proposed grading and scoring system for spina bifida: Spina Bifida Neurological
      Scale (SBNS)
AB  - Neurological symptoms present in neonates with spinal dysraphism often progress
      with growth. A simple, objective scoring system for quantitative analysis of
      spinal neurological deficits, called the Spina Bifida Neurological Scale (SBNS),
      is proposed. Scoring is based on (1) motor function, (2) reflexes, and (3)
      bladder and bowel function. These are each divided into six, four, and five
      points respectively with respect to the level of spinal function. Motor function
      and reflexes are bilaterally analyzed, and the maximum SBNS score of 15 points
      reflects a normal spinal neurological state (grade I). This scoring system was
      correlated with the clinical condition of 89 patients with spina bifida who were
      graded from I to V. A total score of less than 5 was associated with a
      nonambulatory state (grade IV or V) in 84.0% of patients, and a score of 5-9 was
      associated with an ambulatory state (grade III) in 93.8% of patients. Scores of
      10-14 reflected control of bladder and bowel function (grade II) in all patients.
      The application of a standardized scoring scheme will assist in the evaluation of
      patients' clinical status and will enable analysis of chronological changes in
      neurological function.

PMID- 1394283
TI  - Successful surgical obliteration of a huge intradural arteriovenous fistula of
      the spinal cord in a child.
AB  - We report the case of an 8-year-old boy with a huge intradural spinal
      arteriovenous fistula (AVF), which was successfully obliterated by surgery. The
      symptoms were episodic headaches and progressive motor and sensory deficits. He
      had suffered a subarachnoid hemorrhage twice before but no ensuing neurological
      deficits. Neuroradiological examinations revealed an intradural AVF with a huge
      venous aneurysm ventral to the spinal cord of C7 to T2, which was fed by the left
      5th intercostal artery and the right thyrocervical artery. These two feeding
      arteries were occluded intradurally just at the venous aneurysm emerging point.
      MR images taken sequentially after surgery demonstrated complete thrombosis and
      subsequent disappearance of the thrombosed malformation. Neurological symptoms
      improved gradually. Treatment of such malformations is discussed.

PMID- 1394284
TI  - Delayed intraventricular tension pneumocephalus complicating posterior fossa
      surgery for cerebellar medulloblastoma.
AB  - A child is described in whom intraventricular tension pneumocephalus developed 10
      days after removal of a cerebellar medulloblastoma and 1 day after suture
      removal. The tension pneumocephalus was associated with hydrocephalus and CSF
      leakage from the suture line. The symptoms of the pneumocephalus were rapidly
      progressing loss of consciousness and hemiplegia which were promptly reversed
      upon aspiration of the intracranial air. A large amount of intraventricular air
      present in the immediate postoperative period was, however, clinically silent.
      The characteristics of this unusual presentation, its relation to asymptomatic
      pneumocephalus, hydrocephalus and the preventive and therapeutic measures
      required to deal with such conditions are discussed.

PMID- 1394285
TI  - Acute severe combined demyelination.
AB  - We present a second case in which Guillain-Barre syndrome (GBS) and acute
      disseminated encephalomyelitis (ADEM) appeared simultaneously, both in acute and
      fulminant form. The patient, a 10-year-old girl, presented with acute onset of
      coma and flaccid, are-flexic quadriparesis. The elevated CSF protein levels and
      delayed F waves fulfilled the criteria of GBS and an MRI study revealed extensive
      multifocal demyelination compatible with a diagnosis of ADEM. Prompt clinical
      response followed by complete recovery was achieved by treatment with
      corticosteroids. It is suggested that acute severe combined demyelination might
      constitute a separate entity in which the demyelinating process, involving
      simultaneously the central and the peripheral nervous systems, indicates immune
      response against a component of the myelin of one system carrying cross
      antigenicity with the other.

PMID- 1394286
TI  - Spontaneous intracerebral hemorrhage from an unsuspected ependymoma in early
      infancy.
AB  - A case of spontaneous intracerebral hemorrhage from an occipital ependymoma grade
      2 in a 3-month-old boy is reported. The infant died 3 days after surgery. The
      clinical and pathomorphological characteristics are described. Despite the
      usually rich vascularization of these tumors, hemorrhages from intracranial
      ependymomas are relatively uncommon. The different forms and probable causes of
      bleedings are discussed.

PMID- 1394287
TI  - A conformational study of alpha-L-Rhap-(1----2)-alpha-L-Rhap-(1----OMe) by NMR
      nuclear Overhauser effect spectroscopy (NOESY) and molecular dynamics
      calculations.
AB  - The conformational preference of the disaccharide alpha-L-Rhap-(1----2)-alpha-L
      Rhap-(1----OMe) (1) about the glycosidic torsion angles, phi and psi, was studied
      by NMR NOESY spectroscopy and molecular mechanics calculations. The NOE data were
      consistent with either of two distinct conformations close to minima on a
      calculated phi/psi potential energy surface. Starting from the lowest energy
      conformation, a 1-ns molecular dynamics (MD) trajectory was computed in vacuo,
      from which the NOE curves were simulated and compared to the experimentally
      observed NOESY data.

PMID- 1394288
TI  - The use of neocarrabiose oligosaccharides with different length and sulphate
      substitution as model compounds for 1H-NMR spectroscopy.
AB  - The high-field 1H-NMR spectra of various carrageenan oligosaccharides at room
      temperature are given. The assignments were faciliated by the use of proton
      double-quantum coherence (DQCOSY) and 1H-13C chemical shift correlation 2D NMR
      spectroscopy, and by comparing high-field 1H-NMR spectra of various 4-sulphated
      oligosaccharides of the neocarrabiose type. The effects of anomeric configuration
      on the 1H resonances on the same or neighbouring units are discussed. The 13C-NMR
      shift data are given for the tetrasaccharide of kappa-carrageenan.

PMID- 1394289
TI  - Synthesis of D-glucose 3- and 6-[2-(perfluoroalkyl)ethyl] phosphates: a new type
      of anionic surfactant for biomedical use.
AB  - D-Glucose 3- and 6-[sodium 2-(perfluoro-hexyl or -octyl)ethyl phosphates) have
      been synthesized by condensation of 1,2,3,4,-tetra-O-acetyl-beta-D-glucopyranose
      and 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose with 2
      (perfluoroalkyl)ethylphosphoroditriazolides followed by O-deacetylation or
      deacetalation. The structures of the compounds were established on the basis of
      1H-, 19F-, 31P-, and 13C-NMR data. These salts display strong surface activities
      and appear to have good biocompatibility.

PMID- 1394290
TI  - Interaction of linear manno-oligosaccharides with three mannose-specific bulb
      lectins. Comparison with mannose/glucose-binding lectins.
AB  - Three new mannose-binding lectins, isolated from daffodil (NPA), amaryllis (HHA),
      and snowdrop (GNA) bulbs, are capable of precipitating with a linear
      mannopentaose (Man alpha 1-3Man alpha 1-3Man alpha 1-3Man alpha 1-2Man). NPA and
      HHA reacted strongly with the mannopentaose whereas GNA gave a precipitate only
      at concentrations greater than 500 microM. A phosphate group at C-6 of the
      nonreducing terminal mannosyl group prevented precipitation in all three cases.
      The reduced (NaBH4) mannopentaose, Man4Man-ol, did not precipitate with GNA or
      NPA, but was active with HHA. This activity was lost when Man4Man-ol was
      converted (NaIO4 then NaBH4; mild acid hydrolysis of the reduced product) into
      trisaccharide derivatives. With alpha-D-Manp-OMe the three lectins gave UV
      difference spectra having large positive peaks at 292-293 and 283-284 nm, and a
      small positive peak at 275 nm, characteristic of tryptophanyl and tyrosyl
      residues. The association constants for the interaction with alpha-D-Manp-OMe
      were very low (NPA, 86; HHA, 66; and GNA, 41 M-1), but the lectins bound methyl
      (1----3)-alpha-mannobioside with increased affinity (K for NPA 540, for HHA 2400,
      and for GNA 200 M-1). The bulb lectins lack binding sites for hydrophobic
      ligands, as judged by their failure to interact with the fluorescent probes 8
      anilino-1-napthalenesulfonic acid (ANS) and 6-p-toluidino-2-naphthalenesulfonic
      acid (TNS).

PMID- 1394291
TI  - New mannose-specific lectins from garlic (Allium sativum) and ramsons (Allium
      ursinum) bulbs.
AB  - Two new mannose-binding lectins were isolated from garlic (Allium sativum, ASA)
      and ramsons (Allium ursinum, AUA) bulbs, of the family Alliaceae, by affinity
      chromatography on immobilized mannose. The carbohydrate-binding specificity of
      these two lectins was studied by quantitative precipitation and hapten-inhibition
      assay. ASA reacted strongly with a synthetic linear (1----3)-alpha-D-mannan and
      S. cerevisiae mannan, weakly with a synthetic (1----6)-alpha-D-mannan, and failed
      to precipitate with galactomannans from T. gropengiesseri and T. lactis-condensi,
      a linear mannopentaose, and murine IgM. On the other hand, AUA gave a strong
      reaction of precipitation with murine IgM, and good reactions with S. cerevisiae
      mannan and both synthetic linear mannans, suggesting that the two lectins have
      somewhat different binding specificities for alpha-D-mannosyl units. Of the
      saccharides tested as inhibitors of precipitation, those with alpha-(1----3)
      linked mannosyl units were the best inhibitors of ASA, the alpha-(1----2)-, alpha
      (1----4)-, and alpha-(1----6)-linked mannobioses and biosides having less than
      one eighth the affinity of the alpha-(1----3)-linked compounds. The N-terminal
      amino acid sequence of ASA exhibits 79% homology with that of AUA, and moderately
      high homology (53%) with that of snowdrop bulb lectin, also an alpha-D-mannosyl
      binding lectin.

PMID- 1394292
TI  - Anticoagulant and antithrombin activities of oversulfated fucans.
AB  - Three species of oversulfated fucans having different sulfate contents (the ratio
      of sulfate/total sugar residues, 1.38-1.98) were prepared by chemical sulfation
      of a fucan sulfate (sulfate/sugar ratio, 1.28) isolated from the brown seaweed
      Ecklonia kurome. The anticoagulant activities of the oversulfated fucans were
      compared with that of a parent fucan with respect to activated partial
      thromboplastin time (APTT) and thrombin time (TT) in plasma. The respective
      activities (for APTT and TT) of the oversulfated fucans increased to 110-119% and
      108-140% of the original values with increase in their sulfate content. The
      anticoagulant activity with respect to APTT (173 units/mg) of an oversulfated
      fucan (sulfate/sugar ratio, 1.98) was higher than that (167 units/mg) of heparin
      used as a standard. The heparin cofactor II-mediated antithrombin activity of the
      oversulfated fucans also increased significantly with increase in sulfate
      content. The maximum activity was higher than those of the parent fucan and
      heparin. However, the increment of the anticoagulant and the antithrombin effects
      gradually decreased with increase in the sulfate content of the fucans. These
      results indicate that the effects of the fucan sulfate are dependent on its
      sulfate content until a plateau is reached.

PMID- 1394293
TI  - Reaction of 2-deoxy-6-O-[2,3-dideoxy-4,6-O-isopropylidene-2,3- (N-tosylepimino)
      alpha-D-mannopyranosyl]-4,5-O-isopropylidene-1,3-di-N- tosylstreptamine with
      potassium hydrogenfluoride.

PMID- 1394294
TI  - Epimerization of reducing terminal groups of (1----2)-linked D-gluco- and D-manno
      disaccharides in aqueous sodium hydroxide.

PMID- 1394295
TI  - Synthesis of neoglycolipids containing a mucin-type core unit.

PMID- 1394296
TI  - The conformational behaviour of the cardiac glycoside digoxin as indicated by NMR
      spectroscopy and molecular dynamics calculations.
AB  - The 1H- and 13C-NMR spectra of digoxin in solution in Me2SO-d6 have been assigned
      completely. Measurement of the 3JC,H values has enabled estimation of the
      torsional angles involving the bonds linking the digitoxose residues, between the
      inner digitoxose and the genin unit, and for the unsaturated gamma-lactone ring.
      These values have been supplemented by 1H-1H NOE data. In general, there is good
      agreement between the conformations in solution (NMR data) and the solid state (X
      ray data), and that derived from theoretical modelling which shows evidence of
      conformational flexibility. The major difference occurs for the torsion between
      the genin and the innermost digitoxose residue where molecular dynamics predict
      the presence of two conformations, one similar to that seen by NMR and the other
      similar to the X-ray structure.

PMID- 1394297
TI  - Synthesis and X-ray crystal and solution structures of 2,5-anhydro-3,4-O-(1,2
      ethanediyl)-D-mannitol: a locked 4T3 furanose conformer.
AB  - 2,5-Anhydro-3,4-O-(1,2-ethanediyl)-D-mannitol (1) was prepared from 2,5-anhydro-D
      mannitol (2) in three steps. The fused ring system was introduced by a phase
      transfer alkylation using 1,2-dibromoethane. Its conformation in solution was
      determined by NMR studies at 500 MHz. Variable-temperature studies showed no
      lineshape change from 25 to 80 degrees in D2O. The data indicate that the five
      membered ring is locked by the trans-fused six-membered 1,4-dioxane ring into a
      twist 4T3 conformation. A single-crystal X-ray study was carried out. The
      crystals are orthorhombic, C222(1), a = 4.7252 (6), b = 14.0364 (12), c = 13.268
      (2) A, Z = 4, with R = 0.032 for 894 observations. The molecule lies upon a
      crystallographic two-fold axis, and thus the five-membered ring exists in a
      perfect 4T3 conformation with a pseudorotation angle of 0 degree and amplitude of
      47.2 degrees, in agreement with the NMR results. We have shown earlier that,
      among twenty possible conformers, phosphofructokinase acts specifically on the
      4T3 conformer of the beta anomer of D-fructose 6-phosphate.

PMID- 1394298
TI  - Conformational analysis of the anomeric forms of kojibiose, nigerose, and maltose
      using MM3.
AB  - Energy surfaces were computed for relative orientations of the relaxed pyranosyl
      rings of the two anomeric forms of kojibiose, nigerose, and maltose, the (1----2)
      alpha, (1----3)-alpha, and (1----4)-alpha-linked D-glucosyl disaccharides,
      respectively. Twenty-four combinations of starting conformations of the rotatable
      side-groups were considered for each disaccharide. Optimized structures were
      calculated using MM3 on a 20 degree grid spacing of the torsional angles about
      the glycosidic bonds. The energy surfaces of the six disaccharides were similar
      in many respects but differed in detail within the low-energy regions. The maps
      also illustrate the importance of the exo-anomeric effect and linkage type in
      determining the conformational flexibility of disaccharides. Torsional
      conformations of known crystal structures of maltosyl-containing molecules lie in
      a lower MM3 energy range than previously reported.

PMID- 1394299
TI  - Synthesis and properties of sulfated alkyl glycosides.
AB  - Alkyl glycosides were sulfated with sulfur trioxide-pyridine. Dodecyl alpha- and
      beta-D-glucopyranoside gave the corresponding 6-sulfates in 75 and 51% yields,
      respectively. Separation from polysulfated compounds was carried out by reversed
      phase HPLC. Tetradecyl beta-maltopyranoside (16) gave a 88: 12 mixture of 6'- and
      6-sulfates. The sulfated compounds were characterized by 1H-, 13C-, and 2
      dimensional NMR spectroscopy. Surfactant and thermotropic liquid-crystalline
      properties of the sugar derivatives were examined. All of the glycosides show
      smectic phases (SA), and the clearing points rise by introduction of sulfate
      groups. Even glycosides having no unprotected hydroxy groups may show SA-phases
      when bearing sulfate groups. The mesomorphic properties cannot be explained by
      formation of distinct aggregates, but rather must be interpreted by an effective
      intramolecular contrast.

PMID- 1394300
TI  - Synthesis of the methyl thioglycosides of deoxy-N-acetyl-neuraminic acids for use
      as glycosyl donors.
AB  - Methyl 2-thioglycoside derivatives of 4-, 7-, 8-, and 9-deoxy-N-acetylneuraminic
      acids have been prepared as glycosyl donors for the synthesis of
      sialoglycoconjates. Reduction of a (phenoxy)thiocarbonyl group, selectively
      introduced at the 4 position of methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5
      dideoxy-8,9-O-isopropylidene-D- glycero-alpha-D-galacto-2-nonulopyranosid]onate
      (1), gave the 4-deoxy compound, which was transformed via O-deisopropylidenation,
      acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, subsequent
      acetylation, and displacement of the 2-acetoxy group by a methylthio group, into
      methyl (methyl 5-acetamido-7,8,9-tri-O-acetyl-3,4,5-trideoxy-2-thio-D-manno-2-
      nonulopyranosid)onate (17). Methyl [2-(trimethylsilyl)ethyl 5-acetamido-8,9-di-O
      acetyl-4-O-benzoyl- 3,5,7-trideoxy-alpha-D-galacto-2-nonulopyranosid]onate,
      prepared from 1 in five steps, and methyl [2-(trimethylsilyl)ethyl 5-acetamido
      4,7,9-tri-O-acetyl-3,5,8-trideoxy-alpha-D-galacto-2- nonulopyranosid]onate,
      prepared from 1 in six steps, were converted via selective removal of the 2
      (trimethylsilyl)ethyl group, O-acetylation, and displacement of the 2-acetoxy
      group by a methylthio group as described for 17, into the corresponding methyl 7-
      and 8-deoxy-2-thioglycosides. Reductive dechlorination of methyl [2
      (trimethylsilyl)ethyl 5-acetamido-4,7-di-O-benzoyl-9-chloro-3,5,9-trideoxy-D
      glycero-alpha-D-g alacto- 2-nonulopyranosid]onate, prepared from methyl [2
      (trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2
      nonulopyranosid++ +]onate by selective 9-O-tert-butyldimethylsilylation,
      benzoylation, removal of the 9-silyl group, and selective chlorination, gave a 9
      deoxy compound. This was transformed, via O-debenzoylation, O-acetylation,
      selective removal of the 2(trimethylsilyl)ethyl group, 2-O-acetylation, 2
      chlorination, displacement with potassium thioacetate, selective S-deacetylation,
      and S-methylation, into the methyl 2-thio-alpha-glycoside of 9-deoxy-N
      acetylneuraminic acid.

PMID- 1394301
TI  - Synthesis of a series of ganglioside GM3 analogs containing a deoxy-N
      acetylneuraminic acid residue.
AB  - Ganglioside GM3 analogs containing 4-, 7-, 8-, and 9-deoxy-N-acetylneuraminic
      acids in the place of N-acetylneuraminic acid (Neu5Ac) have been synthesized.
      Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)
      (1----4)-2,6-di- O-benzoyl-beta-D-glucopyranoside with the methyl 2-thioglycoside
      derivatives of the respective deoxy-N-acetylneuraminic acids, using
      dimethyl(methylthio)sulfonium triflate as a promoter, gave the four required 2
      (trimethylsilyl)ethyl alpha-sialosyl-(2----3b)-beta-lactosides. These were
      converted via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl
      group, and subsequent imidate formation, into the corresponding alpha-sialosyl-(2
      ---3b)-alpha-lactose trichloroacetimidates 15, 17, 19, and 21. Glycosylation of
      (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 15, 17, 19, and 21 in
      the presence of boron trifluoride etherate afforded the expected beta glycosides,
      which were transformed in good yields, via selective reduction of the azido
      group, coupling with octadecanoic acid, O-deacylation, and de-esterification,
      into the target compounds.

PMID- 1394302
TI  - Regioselectivity of the insertion reactions of some aromatic diazo compound
      complexes with cyclomaltoheptaose.
AB  - Pyrolysis of solid complexes of aromatic diazo compounds with cyclomaltoheptaose
      (beta-cyclodextrin) yields either derivatives via insertion of carbene into
      hydroxyl groups. The distribution of the 2-, 3-, and 6-O-isomers indicates that
      the regioselectivity is moderate. The guest geometry is not as important as its
      size in determining the ratios of regioisomers. The origins of the
      regioselectivity are discussed.

PMID- 1394303
TI  - Synthesis and conformational and NMR studies of alpha-D-mannopyranosyl and alpha
      D-mannopyranosyl-(1----2)-alpha-D-mannopyranosyl linked to L-serine and L
      threonine.
AB  - alpha-D-Mannopyranosyl and alpha-D-mannopyranosyl-(1----2)-alpha-D-
      mannopyranosyl linked to L-serine and L-threonine have been synthesised as model
      substances for the linkage region in certain O-linked glycoproteins. Metropolis
      Monte Carlo simulations were performed with a modified version of the GESA
      program, to yield theoretical NOEs and interatomic distances as ensemble-average
      values, and these were compared with results from steady-state NOE experiments.
      The NOEs were determined as ensemble-average and as global minimum values. NMR
      chemical shift differences, obtained for signals of the glycopeptides relative to
      those of the respective monomers, were interpreted in terms of short inter
      residue atomic distances as found within the global minima, and on the basis of
      averaged distances derived from Monte Carlo simulations.

PMID- 1394304
TI  - Syntheses of branched-chain sugars with push-pull functionality.
AB  - The reaction of methyl 4,6-O-benzylidene-3(2)-deoxy-alpha-D-erythro-
      hexopyranosid-2(3)-ulose with carbon disulfide, alkyl iodide, and sodium hydride
      gave methyl 4,6-O-benzylidene-3(2)-[bis(alkylthio)methylene]-3(2)-deoxy-alpha-D-
      erythro-hexopyranosid-2(3)-uloses. Methyl 4,6-O-benzylidene-2-[bis(methylthio)
      methylene]-2-deoxy-alpha-D- erythro-hexopyranosid-3-ulose (5) reacted with
      aromatic amines to give, in a rearrangement process, N-aryl-2-aryliminomethyl-4,6
      O-benzylidene-2-deoxy- alpha-D-erythro-hex-1-enopy-ranosylamin-3-uloses. The
      reaction of 5 with hydrazine hydrate afforded 5-methylthio-(methyl 4,6-O
      benzylidene-2,3-dideoxy-alpha-D-erythro-hexopyranosido)[3,2- c]pyrazole.

PMID- 1394305
TI  - Structure of the complement-activating proteoglycan from the pilose antler of
      Cervus nippon Temminck.
AB  - An anti-complementary polysaccharide, DWA-2, isolated from an unossified pilose
      antler of C. nippon Temminck by digestion with pronase, gel filtration, and
      affinity chromatography, consisted mainly of GalNAc, GlcA, IdoA, and sulfate in
      the molar ratios 1.0:0.6:0.3:0.8, and small proportions of Man, Gal, GlcNAc, and
      protein (4.5%). Methylation analysis, NMR spectroscopy, and degradation with
      enzymes indicated that DWA-2 contained chondroitin sulfate A-, B-, and C-like
      moieties. DWA-2 showed potent anti-complementary activity, and crossed
      immunoelectrophoresis indicated that it cleaved complement C3 in the absence of
      Ca2+ ion. Digestion of DWA-2 with chondroitinase ABC or ACI reduced the anti
      complementary activity to a low level, but digestion with chondroitinase B
      reduced the activity by approximately 40% and the enzyme-resistant fraction still
      showed a significant activity.

PMID- 1394306
TI  - The structure of the O-specific polysaccharide chain of the lipopolysaccharide of
      Salmonella arizonae O61.
AB  - The O-specific polysaccharide was obtained by mild degradation of the Salmonella
      arizonae O61 lipopolysaccharide with acid. It contained 2-acetamido-2-deoxy-D
      glucose, 2-acetamidino-2,6-dideoxy-L-galactose (FucAm), and 7-acetamido-3,5,7,9
      tetradeoxy-5-[(R)-3-hydroxybutyramido]-D- glycero-L-galacto-nonulosonic acid
      (Sug). On the basis of partial acid hydrolysis with 0.1 M HCl, solvolysis with
      anhydrous HF in methanol, and 1H- and 13C-NMR analysis (including 1H/13C
      inversely correlated spectroscopy for localisation of N-acyl substituents), it
      was concluded that the O-specific polysaccharide had the following structure. ---
      3)-alpha-L-FucAm-(1----3)-alpha-D-GlcNAc-(1----8)-beta-Sug+  ++-(2---- The O
      antigen of S. arizonae O61 is structurally related to that of Pseudomonas
      aeruginosa O12, thus explaining the known serological cross-reactivity between
      these micro-organisms.

PMID- 1394307
TI  - Structure of the D-mannan of the pathogenic yeast, Candida stellatoidea ATCC
      20408 (type II) strain, in comparison with that of C. stellatoidea ATCC 36232
      (type I) strain.
AB  - Acid treatment of the cell-wall D-mannas of Candida stellatoidea strains ATCC
      36232 (Type I, A3 strain) and ATCC 20408 (Type II, A2 strain) gave (1----2)
      linked beta-D-manno-oligosaccharides (dp 2-5), whereas treatment with alkali gave
      the (1----2)-linked alpha-D-mannobiose. Conventional acetolysis of the acid- and
      alkali-treated D-mannan of the A3 strain gave oligosaccharides consisting of (1--
      -2)- and (1----3)-linked alpha-D-mannopyranose residues, similar to those of
      Candida albicans serotype B strain. Mild acetolysis of the acid- and alkali
      treated D-mannan of the A2 strain gave higher oligosaccharides that were digested
      by the Arthrobacter GJM-1 strain exo-alpha-D-mannosidase. The results of 1H- and
      13C-NMR analyses indicated this D-mannan to contain branches with the following
      structures: beta-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp++ +-(1----2)
      alpha-D-Manp- (1----2)-D-Man, beta-D-Manp-(1----2)-beta-D-Manp-(1----2)-alpha-D
      Manp -(1----2)- alpha-D-Manp-(1----2)-D-Man, and beta-D-Manp-(1----2)-beta-D-Manp
      (1----2)-beta- D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp-(1- ---2)-alpha
      D-Manp- (1----2)-D-Man, in common with the D-mannans of C. albicans serotype A
      strains.

PMID- 1394308
TI  - Solution conformation and properties of the galactoglucan from Rhizobium meliloti
      strain YE-2(S1).
AB  - The physicochemical solution properties of the galactoglucan excreted by
      Rhizobium meliloti strain YE-2(S1) have been investigated by capillary
      viscometry, potentiometric titration, isothermal mixing microcalorimetry, and
      circular dichroism. Potentiometric and chiro-optical data, as a function of the
      degree of ionisation, indicate the absence of a co-operative conformational
      transition. Solution properties, as a function of ionic strength and temperature,
      suggest that the galactoglucan adopts a disordered conformation characterised by
      moderate flexibility. Polyelectrolyte theory is used to fit the enthalpy of
      dilution data with a suitable linear charge-density parameter. Conformational
      calculations and chain modelling, using molecular mechanics, give an unperturbed
      characteristic ratio, (C infinity) of 20, which was smaller than that estimated
      from intrinsic-viscosity and molecular-weight data for an expanded-coil chain
      model.

PMID- 1394309
TI  - Structures of the O chains from lipopolysaccharides of Campylobacter jejuni
      serotypes O:23 and O:36.
AB  - Lipopolysaccharides of C. jejuni serotypes O:23 and O:36 have been shown to
      contain structurally variable O polysaccharide chains with repeating units of
      four closely-related types: ----3)-beta-D-GlcpNAc-(1----3)-alpha-D-Galp-(1----2)
      6d-alpha-D-alt-H epp-(1---- , ----3)-beta-D-GlcpNAc-(1----3)-alpha-D-Galp-(1---
      2)-6d-3-Me-alpha-D-alt -Hepp- (1----, ----3)-beta-D-GlcpNAc-(1----3)-alpha-D-Galp
      (1----2)-D-glycero-alpha-D-a lt-Hepp - (1----, and ----3)-beta-D-GlcpNAc-(1----3)
      alpha-D-Galp-(1----2)-3-Me-D-glycero-alph a-D-alt - Hepp-(1----. Structural
      methods included 1H- and 13C-NMR spectroscopy, methylation linkage analysis, fast
      atom bombardment mass spectrometry of methylated glycans, and selective
      fragmentations by the Smith degradation and N-deacetylation-nitrous acid
      deamination.

PMID- 1394310
TI  - Cyclic (1----2)-beta-D-glucans (cyclosophorans) produced by Agrobacterium and
      Rhizobium species.
AB  - Neutral and acidic cyclic (1----2)-beta-D-glucans (cyclosophorans), obtained from
      culture filtrates and cells of Agrobacterium and Rhizobiun, are synthesised on
      the cell surface and then secreted. Eight cyclosophorans with dp 17-24 were
      isolated; all of the strains of Agrobacterium showed almost the same distribution
      pattern, whereas there were three other distribution patterns for the strains of
      Rhizobium.

PMID- 1394311
TI  - Occurrence of 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid as an N-acyl
      substituent in the O-polysaccharide chain of the lipopolysaccharide of Vibrio
      anguillarum V-123.
AB  - A new and highly branched amino acid was found as an N-acyl substituent of the O
      polysaccharide chain obtained from the lipopolysaccharide of Vibrio anguillarum V
      123 (serogroup JO-2) and evidence is presented to support the structure as 2,4
      dihydroxy-3,3,4-trimethylpyroglutamic acid. Acid hydrolysis of the O
      polysaccharide gave the lactone of 2,4-dihydroxy-3,3,4-trimethylglutamic acid,
      together with 2-amino-2-deoxy-D-galacturonic acid, 2-amino-2,6-dideoxy-D-glucose
      (D-quinovosamine), and 4-amino-4,6-dideoxy-D-glucose (D-viosamine). Degradation
      of the O-polysaccharide with hydrogen fluoride yielded a fragment (H1) that was
      indicated by the 1H-NMR data to be 4-amino-4,6-dideoxy-D-glucose N-acetylated
      with 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. The configuration of the
      amino acid was not determined.

PMID- 1394312
TI  - Structure of the O-polysaccharide chain of the lipopolysaccharide of Vibrio
      anguillarum V-123.
AB  - The O-polysaccharide chain (PS-1), released by mild acidic treatment of the LPS
      of V. anguillarum V-123 (serogroup JO-2), a pathogenic bacterium of marine and
      estuarine fish, consists of 2-amino-2-deoxy-D-galacturonic acid, 2-amino-2,6
      dideoxy-D-glucose (D-quinovosamine), and 4-amino-4,6-dideoxy-D-glucose (D
      viosamine) N-acylated with 2,4-dihydroxy-3,3,4-trimethylpyroglutamic acid. Strong
      acid hydrolysis of PS-1 afforded alpha-GalNA-(1----4)-alpha-GalNA-(1----3)-QuiN
      (A1) and alpha-GalNA-(1----3)-QuiN (A2), and hydrolysis with hydrogen fluoride
      gave N-acetylated A1 and 4-amino-4,6-dideoxy-D-glucose N-acylated by 2,4
      dihydroxy-3,3,4-trimethylpyroglutamic acid. Mild treatment of PS-1 with alkali
      removed the N-formyl substituents and Smith degradation of the product gave alpha
      QuiNAc-(1----3)-beta-VioNAcyl-(1----3)-alpha-GalNAc A-(1----3)-2,3,4-
      trihydroxybutanoic acid (S1) and S2 in which the carboxyl group of the GalNAcA
      residue was amidated. Thus, the repeating unit of the O-polysaccharide is----3)
      alpha-GalNAcA(amino)-(1----4)-alpha-GalNFoA-(1----3 )- alpha-QuiNAc-(1----3)-beta
      VioNAcyl-(1----in which the N-Acyl group is 2,4-dihydroxy-3,3,4
      trimethylpyroglutamic acid and Fo is formyl.

PMID- 1394313
TI  - The "pseudo double-helical" structure of the gel-forming capsular polysaccharide
      from Rhizobium trifolii.
AB  - X-ray diffraction analysis of oriented fibers of the gel-forming, neutral, doubly
      branched, galactoserich capsular polysaccharide from Rhizobium trifolii has been
      used to determine and refine the molecular structure to a final R value of 0.28.
      The polysaccharide forms a 2-fold single helix of pitch 20.2 A, is stabilized by
      a series of hydrogen bonds that involve the side chains, and has the appearance
      of a double helix. Packing calculations reveal that the short-range ordering of
      these "pseudo double helices" is brought about by intermolecular hydrogen bonds
      that involve the side chains. Complete or partial removal of side chains will
      weaken the molecular association and is detrimental to the gelation process.

PMID- 1394314
TI  - Structure of the O-specific polysaccharide chain of the lipopolysaccharide of
      Enterobacter agglomerans.

PMID- 1394315
TI  - Structures of the oligosaccharides obtained from the core regions of the
      lipopolysaccharides of Bradyrhizobium japonicum 61A101c and its symbiotically
      defective lipopolysaccharide mutant, JS314.
AB  - The only core oligosaccharide released from the lipopolysaccharide (LPS) of
      Bradyrhizobium japonicum 61A101c by prolonged (5 h) mild hydrolysis with acid,
      and the major core oligosaccharide obtained from its symbiotic and LPS-defective
      mutant, JS314, was the trisaccharide alpha-D-Man p-(1----4)-alpha-D-Glc p-(1---
      4)-2,7-anhydro-alpha-Kdof. The 2,7-anhydro-3-deoxy-alpha-D-manno-2-
      octulofuranosonic acid moiety was probably formed during the prolonged mild
      hydrolysis with acid. A disaccharide core component, also released by mild acid
      hydrolysis of the mutant LPS, had the structure 4-O-Me-alpha-D-Man p-(1----5)
      Kdo. The Kdo residue in this disaccharide is present as the normal pyranose form
      and as an anhydro derivative, possibly 4,8-anhydro-3-deoxy-D-manno-2-octulosonic
      acid, which may have formed also during prolonged mild hydrolysis with acid. Mild
      acid hydrolysis of the LPS of the parent strain does not produce this
      disaccharide, but 4-O-Me-Man is found exclusively in the O-chain fraction
      released from the parent LPS. Additionally, a small amount of O-chain is found in
      the mutant LPS. The results imply that the O-chain is attached to the remainder
      of the LPS through the 4-O-Me-Man-Kdo disaccharide component of the core region.

PMID- 1394316
TI  - Studies of model compounds for the analysis of ester-containing polysaccharides
      by the reductive-cleavage method.
AB  - The four O-propionyl regioisomers of methyl tri-O-methyl-alpha-D-glucopyranoside
      and the 2- and 3-O-propionyl regioisomers of methyl tri-O-methyl-beta-D
      glucopyranoside were subjected to reductive cleavage in the presence of Et3SiH
      and Me3SiOSO2CF3, BF3.Et2O, or Me3SiOSO2Me-BF3.Et2O. The O-propionyl group was
      stable when either Me3SiOSO2CF3 or BF3.Et2O was the catalyst, but was slowly
      reduced to the (1-propyl) ether when Me3SiOSO2Me-BF3.Et2O was the catalyst.
      Reductive cleavages catalyzed by Me3SiOSO2CF3 were complete in 6 h, those
      catalyzed by BF3.Et2O required at least 24 h, and those catalyzed by Me3SiOSO2Me
      BF3.Et2O required 30 min or less. In the alpha-series, the rate of reductive
      cleavage decreased in the order 6-O-propionyl greater than 4-O-propionyl greater
      than 3-O-propionyl much greater than 2-O-propionyl. The reductive cleavage of
      beta anomers was faster than that of the corresponding alpha anomers. This effect
      was particularly striking for the alpha and beta anomers of the 2-O-propionyl
      regioisomer, as would be expected on the basis of a participation reaction.

PMID- 1394317
TI  - Structure of an acidic glycan from the reference strain for Serratia marcescens
      serogroup O22.
AB  - In addition to a neutral glycan, lipopolysaccharide extracts from the reference
      strain for Serratia marcescens serogroup O22 contain an acidic polymer which
      probably defines the serogroup and is of microcapsular origin. The polymer is
      doubly branched with a heptasaccharide repeating unit and a galactan backbone. By
      means of spectroscopic and degradative studies, the structure of the repeating
      unit was established as that shown. [formula: see text]

PMID- 1394318
TI  - The structure of a glycerol teichoic acid-like O-specific polysaccharide of
      Hafnia alvei 1205.
AB  - The O-specific polysaccharide of Hafnia alvei 1205 contained D-glucose, D
      galactose, 2-acetamido-2-deoxy-D-glucose, 4-acetamido-4,6-dideoxy-D-glucose
      (Qui4NAc), glycerol, phosphate, and O-acetyl groups. On the basis of 1D and 2D
      shift-correlated homonuclear and 13C-1H heteronuclear NMR spectroscopy,
      methylation analysis, Smith degradation, and dephosphorylation with hydrofluoric
      acid, it was concluded that the O-antigen was a partially O-acetylated teichoic
      acid-like polysaccharide having the following structure: [formula: see text]

PMID- 1394320
TI  - Pythium aphanidermatum: culture, cell-wall composition, and isolation and
      structure of antitumour storage and solubilised cell-wall (1----3),(1----6)-beta
      D-glucans.
AB  - Under optimal conditions for the culture of the fungus Phytium aphanidermatum, no
      polysaccharides were excreted into the medium. The mycelium contained up to 38%
      of a slightly branched, storage (1----3),(1----6)-beta-D-glucan with a MW of
      20,000. The cell-wall polysaccharides of the mycelium comprised 18% of cellulose
      and 82% of (1----3),(1----6)-beta-D-glucans. Of the non-cellulosic glucans,
      approximately 33% could be solubilised by extraction with water at 121 degrees,
      and they had a MW of 10,000, were highly branched, and contained 6% of (1----6)
      linkages. Treatment of the cell wall with 0.1 M trifluoroacetic acid released
      approximately 50% of the non-cellulosic glucans. The acid-soluble cell-wall (1---
      3),-(1----6)-beta-D-glucans of lower MW (6000) were still highly branched and
      contained 14% of (1----6) and 8% of (1----4) linkages. The storage glucan and the
      hot-water-soluble cell-wall glucan exhibited strong activity against the Sarcoma
      180 in CD-1 mice, whereas the acid-soluble cell-wall glucans were inactive. The
      hot-water-soluble cell-wall glucan was also active against the DBA/2-MC.SC-1
      fibrosarcoma in DBA/2 mice.

PMID- 1394319
TI  - Structure of the exopolysaccharide produced by Lactococcus lactis subspecies
      cremoris H414 grown in a defined medium or skimmed milk.
AB  - The structure of the exopolysaccharide of Lactococcus lactis subsp. cremoris
      H414, isolated from a defined medium or skimmed milk, was established by linkage
      analysis on the native polysaccharide, and by characterisation of oligosaccharide
      fragments, obtained by Smith degradation and partial acid hydrolysis, using
      methylation analysis, FABMS, EIMS, and 1H-NMR spectroscopy. The polysaccharide
      has the branched-pentasaccharide repeating unit: [formula: see text]

PMID- 1394321
TI  - Application of methylation analysis in the determination of the structure of
      disaccharides containing 2,3-diamino-2,3-dideoxy-D-glucose (GlcN3N) associated
      with the backbone of lipid A.

PMID- 1394322
TI  - On the solution properties of bacterial polysaccharides of the gellan family.
AB  - The influence of side chains and substituents on the polyelectrolyte behaviour of
      aqueous solutions of polysaccharides of the gellan family has been studied. The
      results of conductimetric and potentiometric titrations suggest that each of
      these polysaccharides adopts a double-helix conformation. Deacetylation
      destabilises the helix of rhamsan and gellan, and optical rotation data confirm
      these results. The side chain in rhamsan is more flexible and is remote from the
      carboxylate groups, and the behavior of this polysaccharide is similar to that of
      gellan. Gelation of deacetylated rhamsan occurs in the presence of calcium ions.
      The intrinsic viscosity as a function of ionic strength depends on the structure
      of the polysaccharide and on the presence of acetyl groups.

PMID- 1394323
TI  - Mild acetolysis and NMR studies of the D-mannan of Saccharomyces cerevisiae X2180
      1A wild-type strain.

PMID- 1394324
TI  - Structure of the polysaccharide S-84 elaborated by Pseudomonas ATCC 31562:
      depolymerisation using fuming hydrochloric acid.

PMID- 1394325
TI  - Metabolic labelling and partial characterisation of a sulfoglycolipid in
      Trypanosoma cruzi trypomastigotes.

PMID- 1394326
TI  - Determination of the structure of the capsular antigen of Escherichia coli
      O8:K46:H30, using FABMS and 2D-NMR spectroscopy.
AB  - The structure of the capsular antigen from Escherichia coli O8:K46:H30 was
      elucidated by methylation analysis and 1D and 2D 1H- and 13C-NMR spectroscopy,
      and by methylation analysis, 1D- and 2D-NMR spectroscopy, and FABMS of the
      oligosaccharide-alditol obtained after dephosphorylation of the polymer with
      aqueous hydrofluoric acid. The capsular polymer is of the teichoic acid type and
      has the following repeating unit. [Formula: see text]

PMID- 1394327
TI  - The structure of the O-specific polysaccharide from Hafnia alvei strain 38
      lipopolysaccharide.
AB  - The O-specific polysaccharide of the lipopolysaccharide from H. alvei strain 38
      has been established by NMR spectroscopy (13C and 1H) and methylation analysis to
      have the repeating unit-->4)-beta-D-ManpNAc-(1-->4)-alpha-D-GlcpNAc(1-->.

PMID- 1394328
TI  - Taxonomic implication of the apparent undetectability of 3-deoxy-D-manno-2
      octulosonate (Kdo) in lipopolysaccharides of the representatives of the family
      Vibrionaceae and the occurrence of Kdo 4-phosphate in their inner-core regions.
AB  - After conventional hydrolysis of lipopolysaccharides (LPSs), Kdo was not
      detectable by the periodate-thiobarbituric acid test in those of any member of
      Vibrionaceae except the gems Plesiomonas, but phosphorylated Kdo was demonstrated
      after strong-acid hydrolysis. Dephosphorylation, periodate oxidation, and
      methylation analysis of LPS preparations from 7 strains selected from all genera
      of Vibrionaceae, except Plesiomonas, showed that the inner-core region (unlike
      that in enteric Gram-negative bacteria) contains only one molecule of Kdo 4
      phosphate 5-substituted with heptose, a constituent of the distal part of the
      core region, as in enteric bacteria. The undetectability of Kdo in LPS after
      conventional hydrolysis and the occurrence of phosphorylated Kdo in strong-acid
      hydrolysates and of Kdo 4-phosphate in the inner-core region are taxonomic
      characteristics of the family Vibrionaceae.

PMID- 1394329
TI  - GLC-MS of reduced, acetylated, and methylated (2----4)- and (2----8)-linked
      disaccharides of 3-deoxy-D-manno-octulopyranosonic acid (Kdo).
AB  - Synthetic alpha- and beta-(2----4)- and alpha- and beta-(2----8)-linked
      disaccharides of 3-deoxy-D-manno-octulopyranosonic acid (Kdo), of which the
      synthesis of the beta-(2----4)-linked compound is described here, were used to
      develop a simple GLC-MS method for the determination of their anomeric
      configuration. The GLC and GLC-MS data for the reduced and acetylated or
      methylated derivatives of the above compounds indicate the alpha-linked synthetic
      disaccharides to be identical to those isolated from bacterial
      lipopolysaccharides.

PMID- 1394330
TI  - Synthesis and preliminary characterisation of new esters of the bacterial
      polysaccharide gellan.
AB  - Under the appropriate experimental conditions, ethyl, propyl, and
      methylprednisolon-21-yl esters of gellan can be obtained without significant
      degradation. At low degrees of esterification (de), depending on the ester
      moiety, the products are water-soluble, which allows the influence of
      hydrophilicity and charge density on their ability to assume an ordered
      conformation in dilute aqueous solution to be studied. With high de, the products
      were soluble only in organic solvents (e.g., methyl sulphoxide) with good film
      forming capacity. The methylprednisolon-21-yl esters have been characterised in a
      preliminary manner in terms of drug-release kinetics.

PMID- 1394331
TI  - Structure of the core oligosaccharide in the lipopolysaccharide isolated from
      Aeromonas salmonicida ssp. salmonicida.
AB  - The core oligosaccharide isolated from the lipopolysaccharide of Aeromonas
      salmonicida ssp. salmonicida has been investigated by methylation analysis, NMR
      spectroscopy (13C and 1H), oxidation with periodate and chromium trioxide, and
      Smith degradation. The following structure is proposed: [Formula: see text]

PMID- 1394332
TI  - Re-investigation of the structure of the capsular polysaccharide of Klebsiella
      K15 using bacteriophage degradation and inverse-detected NMR experiments.
AB  - The structure of the capsular polysaccharide from Klebsiella K15 has been re
      investigated, principally by 1D and 2D 1H- and 13C-NMR spectroscopy of the
      oligosaccharide-alditol obtained by depolymerisation of the polysaccharide with a
      viral-borne endoglycanase followed by borohydride reduction of the isolated
      repeating oligosaccharide. The capsular polysaccharide was shown to have the
      repeating unit: [Formula: see text]

PMID- 1394333
TI  - Immunohistochemical analysis of lymphocyte subsets infiltrating gastric carcinoma
      after mitomycin C administration.
AB  - The intensity of lymphoid cell infiltration and distribution of lymphocyte
      subsets in tumors were investigated immunohistochemically on tumor tissues
      obtained from 11 patients with gastric carcinoma, who had been treated with
      mitomycin C (MMC), 12 mg/m2, i.v. 5 days before operation. The results were
      compared with those obtained from 24 untreated patients as controls. In the tumor
      tissues from pretreated patients, the intensity of lymphoid infiltration was not
      significantly different from that of untreated patients. However, high-grade
      infiltration of CD4+ cells was observed in 55% of pretreated patients, whereas
      only 8% of control patients exhibited the high-grade infiltration (P < 0.02).
      Since the CD8+ cell infiltration was not significantly altered, the ratio of CD4+
      to CD8+ cells was more frequently estimated to be more than 1 in patients
      pretreated with MMC, as compared to untreated controls (P < 0.02). Further, CD25+
      cells in pretreated tumor tissues were more predominant than those in control
      tumor tissues (P < 0.05). These results suggest that MMC administration induces
      these alterations in lymphocyte subsets in tumor tissue in patients with gastric
      carcinoma.

PMID- 1394334
TI  - Penetration of anti-melanoma immunotoxin into multicellular tumor spheroids and
      cell kill effects.
AB  - In order to gain a better understanding of the interaction between immunotoxins
      and tumor cells at the level of three-dimensional tumor mass, we evaluated the
      cell kill effects of monoclonal antimelanoma-antibody/ricin-A-chain immunotoxin
      (ITN) on melanoma cells in multicellular tumor spheroids (MTS) as well as the
      penetration of ITN into MTS. For Minor melanoma cells in monolayer the ITN
      exerted cytotoxic effects after as little as 1 h of exposure. Increasing exposure
      time resulted in progressive increases in cytotoxic activity. In contrast, the
      cell kill effects of ITN were markedly delayed and reduced when Minor cells were
      in MTS. The ITN cytotoxic effects on the melanoma MTS were more than 100 fold
      less than those in monolayer. Patterns of ITN-induced cytotoxicities for Minor
      and for another melanoma cell line, DND-1A, were comparable. The native ricin A
      was more active against PC-10 squamous lung cancer cells than Minor cells,
      whereas the ITN was more cytotoxic against Minor cells than PC-10 cells, thus
      exhibiting selectivity. An autoradiographic study revealed time-dependent
      penetration of radiolabeled ITN from the surface of Minor MTS into the core.
      Incubation for 1 h resulted in the penetration of ITN into only the two or three
      outer layers of the Minor MTS, and low grain counts. Prolonged exposure resulted
      in inhomogeneous penetration of ITN into almost the entire melanoma MTS.
      Penetration of ITN into PC-10 MTS was extremely poor. The reduced cytotoxicity of
      ITN on melanoma cells in MTS as compared to cells grown in monolayer appears to
      correlate with its inhomogeneous distribution in the MTS. The delayed
      cytotoxicity of ITN is also consistent with its slow penetration into the core of
      the MTS.

PMID- 1394336
TI  - Active specific immunotherapy with Newcastle-disease-virus-modified autologous
      tumor cells following resection of liver metastases in colorectal cancer. First
      evaluation of clinical response of a phase II-trial.
AB  - A group of 23 colorectal cancer patients were treated by a new type of active
      specific immunotherapy (ASI) following complete surgical resection of liver
      metastases (RO resection). For ASI treatment we used a vaccine consisting of 1 x
      10(7) autologous, irradiated (200 Gy) metastases-derived tumor cells incubated
      with 32 hemagglutination units (HU) of Newcastle disease virus (NDV). The
      adjuvant vaccine therapy was started 2 weeks after surgery and was repeated five
      times at 14-days intervals followed by one boost 3 months later. The delayed-type
      hypersensitivity (DTH) skin reactions to the vaccine were measured as well as the
      DTH reactions to a challenge test of 1 x 10(7) non-virus-modified autologous
      tumor cells from liver metastases or 1 x 10(7) autologous normal liver cells. In
      addition 32 HU NDV alone and a standard antigen test (Merieux test) were applied
      pre- and post-vaccination. The vaccination was well tolerated. In 13 of 23
      patients an increasing reactivity against the vaccine was observed during the
      vaccination procedure. Nine patients (40%) experienced an increased DTH
      reactivity against autologous tumor cells following vaccination, while 17% or
      fewer showed an increased reactivity to Merieux test antigens, NDV, or normal
      liver cells. The increased antitumor response was not correlated to
      responsiveness to NDV alone, autologous liver cells, enzymes and culture medium
      used for vaccine preparation or standard antigens (Merieux test). After a follow
      up of at least 18 months 61% of the vaccinated patients developed tumor
      recurrence in comparison to 87% of a matched control groups from the same
      institution that had been only surgically treated. The results of this phase II
      trial are encouraging and should stimulate further prospective randomized
      studies.

PMID- 1394335
TI  - Significant antitumor effect of a synthetic lipid A analogue, DT-5461, on murine
      syngeneic tumor models.
AB  - The antitumor effect of a synthetic lipid A analogue, DT-5461, was investigated
      using syngeneic tumor models in mice. Intravenous injection of DT-5461 into mice
      transplanted with solid tumors of MethA fibrosarcoma, MH134 hepatoma, MM46
      mammary carcinoma, Lewis lung carcinoma (3LL), and colon adenocarcinomas 26 and
      38 resulted in significant reductions in the weight of all tumors except Colon
      26, with marked hemorrhagic necrosis of tumor tissues. Efficacy was almost equal
      to that of an Escherichia coli-type synthetic lipid A (compound 506), and also to
      those of some chemotherapeutics including Adriamycin, mitomycin C, fluorouracil
      and cisplatin. Furthermore, DT-5461 was more effective than other
      immunotherapeutics, including picibanil (OK-432) and lentinan. However, its
      antitumor effects were inferior to those of Adriamycin or OK-432 against the
      malignant ascites caused by intraperitoneal inoculation with MethA or with MH134
      cells; life span was not prolonged by either intraperitoneal or intravenous
      administration. In addition, although DT-5461 showed direct inhibitory effects on
      the in vitro growth of MethA or MH134, these were much weaker than those of
      Adriamycin. These findings clearly indicated that DT-5461 with systemic
      administration is a highly effective antitumor agent on solid tumors, and suggest
      that the antitumor effect of DT-5461 with potent necrotizing activity might
      derive from indirect mechanisms related to the activation of host immune systems
      and not to the weak direct cytotoxicity.

PMID- 1394337
TI  - Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in
      patients with advanced cancer.
AB  - ImuVert, a new biological response modifier, was evaluated for toxicity and
      potential efficacy in patients with advanced cancer. This agent consists of
      sized, labile, natural membrane vesicles associated with ribosomes derived from
      Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural
      killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in
      palpable animal tumor systems. A group of 39 patients with a variety of tumors,
      25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median
      age of 57 years were entered into this trial. ImuVert was administered
      subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were
      evaluated. Flu-like systemic toxicities, including fever, chills, nausea,
      vomiting, diarrhea and hypotension were observed. Erythema, induration and
      tenderness developed at the injection sites. Myelosuppression, thrombocytopenia,
      anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved
      within 24 h. Two patients with nodular lymphoma achieved a partial response and
      two minor responses were seen in patients with glioblastoma and melanoma. On the
      basis of ImuVert's biological activity, and tolerable toxicity it warrants
      further clinical investigation.

PMID- 1394339
TI  - Tumorigenicity of interleukin-2 (IL-2)-cDNA-transfected L1210 lymphoma and its in
      vivo variants is modulated by changes in IL-2 expression; potential therapeutic
      implications.
AB  - To study parameters that affect the tumorigenicity of L1210 lymphoma we have
      analyzed the structure of MHC class I antigens of this tumor. In addition this
      tumor was transfected with interleukin-2 (IL-2) cDNA in order to determine the
      effects of high concentrations of IL-2 within the tumor environment. The
      nucleotide sequence of the class I Kd, Dd and Ld mRNAs from this tumor showed
      that the encoded amino acid sequence of the corresponding antigens is normal,
      thus suggesting that the tumorigenicity of L1210 lymphoma is not due to defective
      antigen presentation to tumor-specific cytotoxic T cells. In contrast, induction
      of IL-2 expression by cDNA transfection led to loss of tumorigenicity of the IL-2
      secreting tumor cells. However, a fraction of long-term-surviving mice developed
      progressively growing variant tumors that showed substantial decrease or loss of
      IL-2 expression. These results suggest that IL-2 secretion by tumors is suicidal
      but, because of tumor heterogeneity, IL-2-loss-variant tumors may arise that are
      able to escape the immune defenses of the host. The observed consistent loss of
      IL-2 expression in variant tumors implies that specific targeting of large
      quantities of IL-2 to tumor cells may be a valuable approach to immunotherapy of
      cancer. In addition we find that under specific gamma ray irradiation IL-2
      secreting tumor cells lose their ability to multiply yet continue to secrete IL-2
      at levels equivalent to those secreted by unirradiated cells. Such IL-2-secreting
      irradiated tumor cells were found to be superior immunogens in comparison to the
      irradiated parental tumor cells, suggesting their use as tumor vaccines.

PMID- 1394338
TI  - Tumor necrosis factor alpha modifies resistance to interferon alpha in vivo:
      first clinical data.
AB  - Patients with Philadelphia-positive chronic-phase chronic myelogenous leukemia
      (CML) resistant to interferon (IFN) alpha were treated in a phase I/II study with
      recombinant human tumor necrosis factor alpha to overcome IFN alpha resistance.
      Doses of 40, 80, 120 or 160 micrograms/m2 TNF alpha were given as 2-h infusions
      on 5 consecutive days every 3 weeks. IFN alpha (4 x 10(6) IU/m2 s.c., daily)
      treatment was continued. Six patients were treated, completing 1-24 (median, 12)
      treatment cycles. Five of the six patients achieved partial hematological
      remission, while the remaining patient had to stop treatment because of WHO grade
      4 thrombocytopenia following the first TNF alpha cycle. No complete hematologic
      remission or cytogenetic improvement was seen. Side-effects were similar to those
      described for both substances alone. Maximum tolerable TNF doses usually varied
      between 80 micrograms/m2 and 160 micrograms/m2. To examine possible pathways of
      TNF activity in these patients, interferon receptor status and (2'-5')
      oligoadenylate synthetase levels were examined in peripheral blood mononuclear
      cells. Both parameters remained unchanged during TNF alpha treatment. These
      preliminary data point to significant clinical efficacy of additionally applied
      TNF alpha in IFN alpha-resistant CML patients.

PMID- 1394341
TI  - Quantitative autoradiographic evaluation of the influence of protein dose on
      monoclonal antibody distribution in human ovarian adenocarcinoma xenografts.
AB  - We studied the effect of monoclonal antibody protein dose on the uniformity of
      radioiodinated antibody distribution within tumor masses using quantitative
      autoradiography. Groups (n = 11-13/group) of athymic nude mice with subcutaneous
      HTB77 human ovarian carcinoma xenografts were injected intraperitoneally with an
      125I-labeled anticarcinoma-associated antigen murine monoclonal antibody, 5G6.4
      using a high or a low protein dose (500 micrograms or 5 micrograms). At 6 days
      post-injection the macroscopic and microscopic intratumoral biodistribution of
      radiolabeled antibody was determined. The degree of heterogeneity of the labeled
      antibody distribution within each tumor was quantified and expressed as the
      coefficient of variation (CV) of the activity levels in serial histological
      sections. Tumors from mice given the 500-micrograms protein doses had
      substantially lower CV values, 0.327 +/- 0.027, than did tumors from animals
      given 5-micrograms protein doses, 0.458 +/- 0.041, (P = 0.0078), indicating that
      the higher protein dose resulted in more homogeneous distribution of
      radioactivity in tumors than did the lower dose. While the percentage of the
      injected dose reaching the tumor was comparable between groups, injecting the
      higher dose of protein resulted in significantly lower tumor to non-tumor uptake
      ratios than those obtained for the lower protein dose. These data indicate, in
      this system, that to achieve more uniform intratumoral antibody (and radiation
      for radioimmunotherapy) delivery, a relatively high protein dose must be
      administered. However, to obtain this increased uniformity, a substantial drop in
      tumor/background uptake ratios was seen. Quantitative autoradiographic evaluation
      of human tumor xenografts is a useful method to assess the intratumoral
      distribution of antibodies.

PMID- 1394340
TI  - Blocked ricin-conjugated T cell immunotoxins: effect of anti-CD6-blocked ricin on
      normal T cell function.
AB  - The biological properties of an immunotoxin composed of an anti-CD6 monoclonal
      antibody conjugated to whole ricin, which had been modified so that the galactose
      binding sites of the B chain were blocked ("blocked ricin"), were examined.
      Treatment of peripheral blood lymphocytes with anti-CD6-blocked ricin for a 24-h
      period prevented T cell proliferation induced by phytohemagglutinin in a dose
      dependent manner with concentrations causing 50% inhibition (IC50) ranging from 5
      pM to 30 pM. In contrast, treatment with either blocked ricin alone or with a
      control immunotoxin prepared with a B-cell-lineage-restricted monoclonal antibody
      gave IC50 values of approximately 2 nM. Although shortening the duration of the
      anti-CD6-blocked ricin treatment to as little as 3 h had little significant
      effect on the observed inhibition, T cell viability experiments demonstrated that
      the magnitude of immunotoxin-induced killing after a given time period is
      significantly higher when the target cells become activated. Thus, from the
      initial concentration of cells treated with anti-CD6-blocked ricin placed in
      culture, 40%-45% viable cells remained after 2 days yet only 3%-9% remained if
      phorbol ester and Ca2+ ionophore were added; activation of T cells after mock
      treatment using blocked ricin plus nonconjugated anti-CD6 demonstrated that this
      effect was not the result of activation alone. The toxicity of anti-CD6-blocked
      ricin was also measured by inhibition of PHA-induced clonogenic growth of normal
      T cells. Continuous treatment of the cells using anti-CD6-blocked ricin at 0.1 nM
      resulted in a surviving fraction of about 3.5 x 10(-3); when immunotoxin
      treatment was for 24 h or less, the surviving fraction was only about 10(-1). As
      an indication of the unique specificity of anti-CD6-blocked ricin, immunotoxin
      pretreatment of potential responder cells prevented the generation of allogeneic
      cytolytic T lymphocytes in mixed lymphocyte cultures yet had little effect on the
      generation of interleukin-2-induced lymphokine-activated killer cell activity. We
      conclude that anti-CD6-blocked ricin demonstrates a cellular specificity and
      potency that make it a highly promising anti-T cell reagent.

PMID- 1394342
TI  - Antitumour activity of a sterically blocked ricin immunotoxin on a human
      colorectal adenocarcinoma grafted subcutaneously in nude mice.
AB  - We prepared a ricin-antibody conjugate, lacking the ability to bind the
      galactosidic residues of Sepharose 6B, a so-called blocked immunotoxin. The
      monoclonal antibody AR-3 was cross-linked to ricin through a thioether bond.
      Further studies showed that the immunoconjugate suppressed the tumour growth of
      HT-29 cells in intraperitoneally grafted nude mice, without showing any
      undesirable ricin toxicity. In this work, to demonstrate the therapeutic activity
      of the AR-3-ricin conjugate injected into mice bearing subcutaneous tumour, we
      first evalauted its pharmacokinetic behaviour and biodistribution. The behaviour
      of the immunoconjugate injected intravenously was almost intermediate between
      that of the antibody and ricin. Moreover, when the immunotoxin was intravenously
      administered to nude mice bearing subcutaneous tumour, no therapeutic effects
      appeared, in accordance with the relatively low permeability of the immunotoxin
      from the blood to the skin. In contrast, peritumoral treatment produced a strong
      reduction of the neoplastic nodules without substantial regrowth of the malignant
      cells. This result was also achieved when the immunotoxin treatment was performed
      on a well-established tumour. This finding was strictly related to the specifcity
      of the immunoconjugate, since the analogous treatment with an irrelevant
      immunotoxin showed therapeutic failure.

PMID- 1394344
TI  - A new 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
      for testing macrophage cytotoxicity to L1210 and its drug-resistant cell lines in
      vitro.
AB  - Activated by interferon gamma (IFN gamma)(50 U/ml) and lipopolysaccharide (50
      ng/ml), mouse peritoneal macrophages were cocultured with the L1210 parental cell
      line (L1210/PRT) and its Adriamycin-, cisplatin-resistant cell lines (L1210/ADM,
      L1210/CDDP) for 24 h at effector: target (E:T) ratios of 10:1, 5:1 and 2:1. The
      direct 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide (MTT)
      cleavage assay, a new improved indirect MTT assay, and the colony-formation assay
      were used to quantify macrophage-mediated suppression of these non-adherent
      tumour targets. The results showed that the macrophages can produce formazan at a
      high level, which can interfere with the final results of a direct MTT assay. The
      new indirect MTT assay can avoid such interference because the effectors are
      separated from the targets before the assay is performed, so the real viability
      of the targets is reflected. An indirect MTT assay, as developed in this study,
      could be better than the direct assay for examining the suppressive effect of
      activated macrophages on non-adherent tumour cells in vitro. This study also
      revealed that all the L1210 cell lines can be suppressed significantly by the
      macrophages at E:T ratios of 10:1 and 5:1 while the two drug-resistant cell lines
      have lower survival rates at an E:T ratio of 10:1, indicating that they are more
      susceptible than their parental cell line.

PMID- 1394345
TI  - T lymphocyte killing by a xanthine-oxidase-containing immunotoxin.
AB  - We report on the preparation of an immunotoxin consisting of xanthine oxidase, a
      free-radical-producing enzyme, covalently linked to an anti-CD3 monoclonal
      antibody. The immunotoxin retained both enzymic and immunological properties and
      its toxicity to target cells (a) was greater than that of the free enzyme, (b)
      was proportional to the enzyme concentration, and (c) was reduced either in the
      absence of hypoxanthine or by an excess of free anti-CD3 monoclonal antibody. The
      cytotoxicity and selectivity of the hypoxanthine/conjugated xanthine oxidase
      system were potentiated by the addition of chelated iron and by washing away the
      unbound immunotoxin prior to the addition of substrate. The same system was not
      toxic to bone marrow progenitor cells. A possible use of this immunotoxin for the
      ex vivo purging of organs to be transplanted from T lymphocytes, to avoid the
      graft-versus-host reaction, is suggested.

PMID- 1394343
TI  - Immunological evaluation of patients with hematological malignancies receiving
      ambulatory cytokine-mediated immunotherapy with recombinant human interferon
      alpha 2a and interleukin-2.
AB  - Immunological parameters were evaluated in patients treated with cytokine
      mediated immunotherapy (CMI) consisting of low doses of recombinant human
      interferon alpha 2a (rIFN alpha) and recombinant human interleukin-2 (rIL-2)
      administered either concomitantly or sequentially by subcutaneous self-injections
      in an outpatient setting. Twenty-six patients with hematological malignancies and
      2 metastatic melanoma patients in a progressive stage were enrolled in this
      clinical trial. Of the 26 patients, 24 were at a stage of minimal residual
      disease, including 14 patients who had received autologous bone marrow
      transplantation (ABMT) 2-5 months previously, 7 chronic myelogenous leukemia
      (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1
      mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted
      cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK
      sensitive (K562) target cells was assessed before, during and after CMI, either
      in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2
      activation (induced activity). Spontaneous killing activity was low prior to
      treatment, but increased upon termination of treatment in 10/15 evaluated cycels.
      rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8
      patients after one and two cycles, respectively, of sequential treatment, as well
      as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of
      concomitant treatment. Activation of the T cell mitogenic response was
      demonstrated in 6/9 patients after concomitant CMI, while no such effect was
      observed throughout a sequential treatment in lymphoma and leukemia patients
      after ABMT. Although a direct correlation between immune stimulation and the in
      vivo antitumor response cannot yet be determined, our clinical observations
      support a beneficial therapeutic effect in a substantial number of patients.
      These results indicated that the ambulatory CMI protocol of rIL-2 and rIFN alpha
      could stimulate the host defense immune system and may be helpful in mediating
      the in vivo antitumor response in patients with minimal residual disease.

PMID- 1394346
TI  - Confusion about the tissue distribution of lymphokine-activated killer (LAK)
      cells.

PMID- 1394347
TI  - Is regression of atherosclerosis possible?

PMID- 1394348
TI  - [The antianginal effects of a new delayed-release formulation of diltiazem in
      patients with stable angina pectoris: its evaluation by the ergometry test and
      dynamic electrocardiogram].
AB  - The antianginal efficacy and duration of action of slow-release (SR) diltiazem
      were evaluated in 12 patients with stable angina. Patients underwent maximal
      symptom limited bicycle exercise testing and 24-hour Holter monitoring at the end
      of 1-week placebo run-in phase and after 1-month therapy with either placebo or
      SR-diltiazem (120 mgs bid) using a placebo controlled, double-blind, randomized
      cross-over trial. No concomitant antianginal therapy, except sublingual
      nitroglycerin, was allowed during the trial. Exercise testing was performed 3 and
      12 hours after drug administration. Blood samples were obtained for the
      determination of diltiazem plasma concentrations. After diltiazem administration,
      peak exercise duration increased significantly in comparison both with placebo
      and the run-in phase: from 292 +/- 48 to 378 +/- 113 s at 3 hours and from 286 +/
      59 to 366 +/- 109 s 12 hours after drug administration. Similarly, ST depression
      time increased from 240 +/- 59 to 374 +/- 123 s at 3 hours and from 231 +/- 57 to
      332 +/- 123 s 12 hours after diltiazem. No significant changes of heart rate,
      blood pressure and double product were detected. Diltiazem plasma concentrations
      averaged, respectively, 175 +/- 86 pg/ml and 109 +/- 43 pg/ml 3 and 12 hours
      after its administration. No correlation was found between plasma concentrations
      and antianginal effects of diltiazem. At 24 hours Holter monitoring, SR-diltiazem
      induced a significant decrease of mean heart rate with a reduction in the number
      and duration of ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394349
TI  - [Aortic stenosis and coronary pathology. Their implications for the transvalvular
      gradient].
AB  - To assess the incidence of coronary artery disease in patients with valvular
      aortic stenosis and its implication on peak systolic valvular gradient, 31
      consecutive patients who underwent cardiac catheterization were examined.
      Associated significant coronary artery disease (> 50% reduction in luminal
      diameter evaluated in proximal segments and right dominant circulation) was
      present in 54.8% of patients. There was no difference in the distribution of risk
      factors among patients with and without significant luminal narrowings. The
      prevalence of coronary artery disease was found not to be significantly
      correlated with age (p = 0.276). There was no relationship between typical angina
      pectoris and the presence of coronary artery disease (p = 0.063). Fourty-seven
      percent of cases resulted free of chest pain. Ejection fraction was found to be
      significantly lower in patients with coronary artery disease (45 +/- 14.2%) than
      in patients without coronary artery disease (65.1 +/- 3.9%; p = 0.03) and a
      reverse relationship was observed between the presence of coronary artery disease
      and peak systolic valvular gradient (p = 0.006) which, in turn, correlated
      significantly with ejection fraction (r = 0.68; p = 0.023). These data
      demonstrate that the value of peak systolic valvular gradient, as the only index
      for the evaluation of the severity of aortic stenosis, is greatly limited in
      patients with associated coronary artery disease. Moreover, confirming the
      guidelines of the American College of Cardiology and of the American Heart
      Association task force, these data also stress the necessity of performing
      coronary angiography regardless angina pectoris is present or not.

PMID- 1394350
TI  - [Angioplasty in total occlusion of the coronary arteries: the importance of the
      angiographic variables].
AB  - Total coronary occlusions can be treated by coronary angioplasty with a lower
      success rate when compared to the angioplasty success rate of stenoses. To
      evaluate factors associated with successful re-opening of total coronary
      occlusion we evaluated 128 occlusions attempted in 120 patients. We analyzed
      clinical and angiographic variables. Successful re-opening was obtained in 65% of
      total occlusions attempted; 1 patient (0.8%) had to undergo emergency coronary
      artery bypass surgery. Only the morphological characteristics of the occlusions
      were predictive of success. When total occlusions had a tapered morphology,
      success was achieved in 87% of the attempts versus 50% of success without tapered
      morphology (p < 0.001). The success, when the occlusion was associated with the
      presence of bridging collaterals, was very low (present: 30% success; absent: 71%
      success, p < 0.005). Success for occlusions longer than 1.5 cm was lower when
      compared to shorter occlusions (61% vs 78%; p < 0.005). The type of occlusion
      (absolute, functional), the presence of a branch originating at the level of the
      occlusion, the duration of the occlusion, the artery and its segment were not
      predictive of success. Multivariate analysis showed that tapered morphology was
      the only variable associated with successful re-opening of a total occlusion (87%
      probability of success when present). We conclude that it is possible to re-open
      a total coronary occlusion with low complication rate and high primary success
      rate when careful care is applied with particular attention paid to the
      morphology of the occlusion.

PMID- 1394351
TI  - [Increased serum levels of IgA and C4 in atherosclerosis: the absence of a
      correlation with the arteriographic picture].
AB  - We have previously shown that an increase in serum IgA and C4 is often detectable
      in presence of diffuse atherosclerotic disease. The present study was performed
      to verify such results in a different and larger sample of subjects, and to
      ascertain whether the above immunologic variables are correlated with the
      severity of atherosclerotic disease. Seventy-three atherosclerotic subjects with
      at least 1 significant (> 75%) stenosis in a major arterial branch were selected
      according to the reports of arterial panangiographies performed previously. Among
      them, 36 subjects (24 men and 12 women, mean age 63 +/- 7 years) were singled
      out, who matched by age and sex 36 control subjects (mean age 63 +/- 7 years). In
      all of these subjects the following serum immunologic and lipid variables were
      measured: IgG, IgA, IgM, IgE, C3, C4, total cholesterol, HDL-cholesterol and
      triglycerides. With respect to the controls, the 36 matched atherosclerotic
      subjects had higher levels of IgA (263.0 +/- 119.8 vs 334.3 +/- 130.5 mg/dl; p =
      0.0126), C4 (25.7 +/- 5.8 vs 30.4 +/- 9.1 mg/dl; p = 0.0297) and triglycerides
      (153.1 +/- 77.3 vs 209.7 +/- 141.3; p = 0.0500). No correlation was found between
      the number of arterial stenoses (range 1-8, mean 2.9 +/- 1.5) and any of the
      immunologic or lipid parameters in all the 73 atherosclerotic subjects. Only the
      daily cigarette consumption was correlated with the disease extension (tau =
      0.1984; p = 0.0392).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394352
TI  - [The coronary angioplasty of oversized vessels by the hugging-balloon and single
      guiding-catheter technic: a case report].
AB  - A case is described of percutaneous coronary angioplasty performed on an
      oversized right coronary artery (> 7 mm), using the hugging balloon technique.
      The procedure and the equipment utilized are described.

PMID- 1394353
TI  - [Echocardiography in the cardiac intensive care unit: new technologies in the
      assessment of ischemic cardiopathy].

PMID- 1394354
TI  - Distribution and size of particles after dynamic angioplasty in cadaveric
      arteries with the Kensey catheter system: a comparison with clinical experience.
AB  - The distribution and size of atheromatous debris after angioplasty with the
      Kensey catheter was determined after recanalization of 18 segments of human
      cadaveric superficial femoral arteries (SFA). The debris produced was studied
      cytologically and measured semiquantitatively. Nearly 80% of all particles ranged
      from 5 to 15 microns, approximately the size of red blood cells. More than 20% of
      all particles exceeded this size and 2% were larger than 100 microns. The use of
      the Kensey catheter dynamic angioplasty system in the lower extremities contains
      the risk of embolic complications because more than 20% of all particles are
      larger than human blood cells. Seven patients with occlusion and 3 with stenoses
      of the SFA were treated with the Kensey catheter system. Recanalization was
      successful in all and in 1 case, small emboli in the anterior tibial artery were
      observed. There was a 50% restenosis/reocclusion rate between 2 weeks and 10
      months.

PMID- 1394356
TI  - Percutaneous transluminal angioplasty of tibial arteries for limb salvage.
AB  - Percutaneous transluminal balloon angioplasty (PTA) was performed in 17 tibial
      arteries with an average cross-sectional area stenosis of 92% (range 75-99%) in
      13 patients (14 limbs) for limb salvage. In 4 of 14 lower extremities, PTA of
      femoropopliteal arteries was also performed. Technical success with 50% or less
      residual stenosis was achieved in all 17 tibial vessels. At approximately 2
      months after PTA, clinical improvement had occurred in 10 of 14 limbs; no patient
      was made worse. Most recent follow-up (mean 19 months, range 8-34 months)
      revealed continued satisfactory clinical success with no further vascular
      intervention in 9 of these 10 limbs (one patient died). Short segmental stenoses,
      residual stenoses less than 40% following PTA, and absence of diabetes or
      gangrene appear to be predictors of favorable clinical outcomes. Our results
      suggest that PTA of focal tibial stenosis is an effective and safe treatment
      modality in properly selected patients and that wider use of PTA may be
      justified.

PMID- 1394355
TI  - Percutaneous transluminal angioplasty for occlusion of the subclavian artery:
      short- and long-term results.
AB  - Percutaneous transluminal angioplasty was performed in 8 symptomatic patients
      with proximal occlusion of the left subclavian artery. Technical and short-term
      clinical success was achieved in 7 cases. Nonoccluding embolization to the distal
      subclavian artery and stenosis of the brachial artery after a combined
      femoral/brachial approach occurred as complications in 2 patients. Three patients
      are asymptomatic with a patent subclavian artery 25, 28, and 37 months after
      angioplasty. Reobstructions in 4 patients occurring after 8, 12, and 16 months
      were retreated by angioplasty (3 patients) and stent implantation (1 patient with
      a second restenosis) with good technical and clinical success. Long-term patency
      was less than 50%, but successful retreatment is feasible. Therefore, we consider
      percutaneous transluminal angioplasty a reasonable therapeutic option in patients
      who are not surgical candidates.

PMID- 1394357
TI  - Strecker stent in stenotic hemodialysis Brescia-Cimino arteriovenous fistulas.
AB  - Flexible tantalum stents (Strecker) were used as an adjunct to percutaneous
      transluminal angioplasty (PTA) in the treatment of stenotic arterial or venous
      limbs of Brescia-Cimino hemodialysis fistulas. The diagnostic procedure was
      performed using retrograde fistulography. After PTA with unsatisfactory results,
      stents were placed in 5 patients with significant residual stenoses and poor
      fistula function. Within the mean follow-up period of 6.4 months (range 3-10
      months) all fistulas were functioning. We conclude that Strecker stent is useful
      in the treatment of stenotic hemodialysis arteriovenous fistulas as an adjunct to
      PTA.

PMID- 1394358
TI  - Percutaneous transcatheter ethanol sclerotherapy of postoperative pelvic
      lymphoceles.
AB  - Although percutaneous procedures have been used for the treatment of lymphoceles,
      transcatheter sclerosing therapy has not been widely applied. We present the
      results of transcatheter sclerotherapy of lymphoceles with 96% absolute ethanol
      in 7 patients who had developed lymphocele after pelvic lymphadenectomy for
      uterine cancer. Seven of the eight lymphoceles (88%) completely disappeared after
      treatment. The duration of catheter drainage ranged from 4 to 21 days. Although
      one lymphocele did not resolve completely, it did not require surgery as the
      patient's symptoms resolved.

PMID- 1394359
TI  - Pulse-spray pharmacomechanical thrombolysis.
AB  - The synergistic potential of combining pharmacologic and mechanical methods of
      thrombolysis has recently been recognized. Pulse-spray pharmacomechanical
      thrombolysis is one such method, which in our experience has markedly increased
      the efficiency and acceptability of thrombolysis. With this technique, dialysis
      grafts usually require only 20-35 min for thrombolysis; bypass grafts or native
      arteries usually require 60-150 min. The entire procedure is accomplished in one
      session within the angiography suite, including the supplemental transluminal
      angioplasty, atherectomy, or stenting that is usually also necessary. Clear
      understanding of the principle of the method and meticulous attention to
      technical details is essential for maximal speed, safety, and efficacy.

PMID- 1394360
TI  - Thrombosis of the popliteal vein.
AB  - Among 3,307 consecutive patients (3,556 legs) with deep venous thrombosis, 54
      (1.5%) showed an isolated thrombus of the popliteal vein on phlebography. The
      majority of those had a history of "effort" or long lasting flexion during air or
      bus travel. Forty-four percent suffered from pulmonary embolism as the first sign
      of deep venous thrombosis. Functional phlebography demonstrated the primary site
      of thrombosis at folds forming in the vein wall at flexion. In order to further
      elucidate the pathogenetic mechanism, 158 popliteal veins were examined
      phlebographically in different functional states revealing age-related
      characteristic wall patterns of rings and folds in flexion causing transient
      impairment of flow. Complementary morphological studies of 120 popliteal veins
      during autopsy showed a transverse rippling of the vein wall caused by intimal
      fibrosis and partial atrophy of the media corresponding to the phlebographic
      findings. It is concluded that microtrauma during effort in combination with
      impaired venous backflow and fibrotic transformation of the venous wall can lead
      to thrombus formation in the popliteal vein.

PMID- 1394361
TI  - Hypoplastic superficial femoral artery associated with bilateral persistent
      sciatic arteries: a diagnostic pitfall.
AB  - A patient with unsuspected bilateral persistent sciatic arteries (PSAs) underwent
      angiography following a gunshot wound to the right thigh. A hypoplastic
      superficial femoral artery associated with this rare vascular anomaly was
      misdiagnosed as being traumatically occluded. Pitfalls in the diagnosis of PSA as
      well as the embryology, clinical features, and complications are discussed.

PMID- 1394362
TI  - Angiographic findings in a patient with primary antiphospholipid syndrome: case
      report.
AB  - A case of antiphospholipid syndrome (APPS) is presented. A 33-year-old female
      presented with a right hemispheric stroke secondary to thrombosis of the middle
      cerebral artery. Shortly thereafter, she developed thrombosis of the right
      brachial artery. Despite thrombolytic therapy, progressive occlusion of this
      artery occurred as demonstrated by a follow-up angiogram. The patient had a
      history of multiple recurrent spontaneous abortions. Lupus anticoagulant,
      anticardiolipin antibodies, and VDRL were positive on two different occasions.
      The angiographic findings of multiple and progressive arterial thrombosis in
      young women should alert the angiographer to the possibility of APPS.

PMID- 1394363
TI  - Dissolution of multiple biliary duct stones using methyl tert-butyl ether (MTBE):
      experience in two cases.
AB  - Methyl tert-butyl-ether (MTBE) was successfully used for stone dissolution in 2
      patients with multiple bile duct cholesterol stones. The presence of a biliary
      enteric anastomosis precluded the endoscopic approach. Because of leakage of MTBE
      into the bowel, dissolution time ranged from 7.5 to 36 h. No significant
      complications other than mild nausea were encountered. No recurrence of stone
      formation has been found at a follow-up varying from 9 to 12 months.

PMID- 1394364
TI  - Modified Tru-Cut needle with exchangeable blunt stylet for safe puncture:
      technical note.
AB  - A modified Tru-Cut needle has been developed to safely bypass interposed vital
      structures during large-bore biopsies of solid lesions in various regions of the
      body. The needle allows blunt advancement in critical locations and facilitates
      accurate pin-point advancement when needed. The needle performed as designed in
      computed tomography (CT)-guided biopsies of 31 solid lesions.

PMID- 1394365
TI  - Contrast injection around mandril wire of an Accustick system using an extension
      tubing: technical note.
AB  - We describe a technique for injecting contrast material around a mandril wire of
      an Accustick access system through the outer 6 French sheath of this system, thus
      identifying the position of the wire. This is accomplished by using an extension
      tubing.

PMID- 1394367
TI  - Preparatory sensory information for cardiac catheterization.

PMID- 1394366
TI  - Percutaneous hepaticoneojejunostomy and choledochocholedochal reanastomosis using
      metallic stents: technical note.
AB  - A new, nonsurgical approach to biliary duct reconstruction in two high-operative
      risk patients is presented. The first patient with an obstructed
      hepaticojejunostomy underwent such reconstruction by placement of Wallstent,
      which remained patent 9 months until death from recurrent tumor. The second
      patient with an inadvertently ligated common bile duct underwent a combined
      percutaneous transhepatic-retrograde endoscopic reconstruction with placement of
      a Gianturco-Rosch (GR) stent. Because of occlusion by granulation tissue 5 months
      later, a new GR stent covered with a silicone membrane was placed within the
      initial stent. Nine months after the second GR stent placement there is no
      evidence of obstruction.

PMID- 1394368
TI  - Effect of monensin on the neuronal ultrastructure and endocytic pathway of
      macromolecules in cultured brain neurons.
AB  - 1. The endocytic pathway of horseradish peroxidase (HRP) was investigated in the
      perikarya of cultured neurons by electron microscopy and enzyme cytochemistry.
      The tracer was observed in endocytic pits and vesicles, endosomes, multivesicular
      bodies, and lysosomes. It took approximate 15 min for the transfer of HRP from
      the exterior of the cell to the lysosomes. 2. Monensin induced distension of the
      Golgi apparatus and formation of intracellular vacuoles. When neurons were
      incubated with both monensin and HRP for 30 to 120 min, the number of HRP-labeled
      endosomes was greater than that in the monensin-free group, whereas the reverse
      was seen for HRP-positive lysosomes. The formation of HRP-positive lysosomes in
      monensin-treated cells was blocked by 47 to 79%. 3. These results indicate that
      the intracellular transport of the endocytosed macromolecule is pH dependent. It
      is also possible that the export of lysosomal enzymes is inhibited by monensin,
      resulting in an accumulation of the endosomes and a reduction of the lysosomes.

PMID- 1394369
TI  - Choline acetyltransferase expression studied with an oligonucleotide probe.
AB  - 1. The localization of choline acetyltransferase messenger RNA has been studied
      using a digoxigenin-tailed complementary oligodeoxynucleotide probe for in situ
      hybridization. 2. Putative cholinergic cells of the rat and ferret spinal cord
      and the ferret retina were labeled. 3. This technique affords superior resolution
      compared to radioactively labeled probes, with apparently equal sensitivity.

PMID- 1394370
TI  - A topography and ultrastructural characterization of in vivo 5,7
      dihydroxytryptamine-labeled serotonin-containing neurons in the central nervous
      system of Aplysia californica.
AB  - 1. Several weeks after administration of 5,7-dihydroxytryptamine (5,7-DHT) to
      Aplysia, a dark pigmentation appears in serotonin-containing neurons, and this
      pigmentation allows visual identification of serotonergic neurons but does not
      appear to alter their physiology. 2. We have determined the distribution of
      labeled nerve cell bodies in the various ganglia of Aplysia and have
      characterized the pigment containing structures in both control and labeled
      neurons. 3. All neurons in this preparation, whether or not they utilize
      serotonin as a transmitter, contain pigment granules, and three types of pigment
      granules can be distinguished. After 5,7-DHT a new type of granule appears in
      serotonergic neurons, probably reflecting lysosomes that have accumulated
      serotonergic synaptic vesicles that contain the oxidized 5,7-DHT. 4. It remains
      unclear why this substance does not cause neurotoxicity in mollusks as it does in
      mammalian preparations.

PMID- 1394372
TI  - [Pneumocystis carinii today--40 years later].
AB  - Forty years ago Czech scientists, J. Vanek and O. Jirovec, diagnosed Pneumocystis
      carinii as the agent of interstitial plasmocytic pneumonia in weak infants. At
      present it is the most frequent pulmonary pathogenic organism in patients
      suffering from AIDS. In the submitted paper the author summarizes experience and
      recent findings on the aetiopathogenesis, pathology, clinical picture, diagnosis,
      treatment and prevention of pneumocystis pneumonia.

PMID- 1394373
TI  - [Smokeless tobacco--also a danger to us?].
AB  - As a result of the decline in the prevalence of smoking in Western countries
      another form of tobacco addiction is developing in the shape of moist snuffs from
      which nicotine is released in the mouth. The addiction which develops is serious,
      as most people who use this form of tobacco belong to young or very young age
      groups. The highest prevalence is at present in Sweden and the United States, in
      western European countries this drug addiction is not as frequent. The authors
      discuss the impact on health, forms and types of moist snuff and of
      advertisements focused on young age groups. It is important to become familiar
      with these data and facts and focus attention on prevention.

PMID- 1394371
TI  - Isoprenylation and carboxylmethylation in small GTP-binding proteins of
      pheochromocytoma (PC-12) cells.
AB  - 1. A group of 21 to 24-kDa proteins of pheochromocytoma (PC-12) cells was found
      in blot overlay assays to bind specifically [alpha-32P]GTP. Binding was inhibited
      by GTP analogues but not by ATP. Such small GTP-binding proteins were found in
      the cytosolic and in the particulate fraction of the cells, but they were
      unevenly distributed: about 75% of the small GTP-binding proteins were localized
      within the particulate fraction of the cells. Separation of these proteins by two
      dimensional gel electrophoresis revealed the existence of seven distinct [alpha
      32P]GTP-binding proteins. 2. Targeting of the small GTP-binding proteins to the
      particulate fraction of PC-12 cells requires modification by isoprenoids, since
      depleting the cells of the isoprenoid precursor mevalonic acid (MVA) by the use
      of lovastatin resulted in a 50% decrease in membrane-bound small GTP-binding
      proteins, with a proportionate increase in the cytosolic form. This blocking
      effect of lovastatin was reversed by exogenously added MVA. 3. In addition,
      metabolic labeling of PC-12 cells with [3H]MVA revealed incorporation of [3H]MVA
      metabolites into the cluster of 21 to 24-kDa proteins in a form typical of
      isoprenoids; the label was not removed from the proteins by hydroxylamine, and
      labeling was enhanced in cells incubated with lovastatin. The latter effect
      reflects a decrease in the isotopic dilution of the exogenously added [3H]MVA, as
      the addition of exogenous MVA reversed the effect of lovastatin on [3H]MVA
      metabolite incorporation into the 21 to 24-kDa proteins. 4. Additional
      experiments demonstrated that isoprenylation is required not only for membrane
      association of small GTP-binding proteins, but also for their further
      modification by a methylation enzyme. This was evident in experiments in which
      the cells were metabolically labeled with [methyl-3H]methionine, a methylation
      precursor. The group of 21 to 24-kDa proteins was labeled with a methyl-3H group
      in a form typical of C-terminal-cysteinyl carboxylmethyl esters. Their
      methylation was blocked by the methylation inhibitors methylthioadenosine (MTA),
      3-deazadenosine and homocysteine thiolactone as well as by lovastatin. MVA
      reversed the lovastatin block of methylation. 5. Two-dimensional gel analysis of
      the [3H]methylated proteins detected seven methylated small GTP-binding proteins
      that correspond to the isoprenylated proteins. Levels of the small GTP-binding
      proteins as well as isoprenylation and methylation were reduced by cycloheximide.
      6. Distribution of the methylated proteins between particulate and cytosolic
      fractions was found to be similar to that of the small GTP-binding proteins
      (i.e., a 4:1 ratio).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1394374
TI  - [Pneumocystis carinii infection after kidney transplantation].
AB  - The authors demonstrate on the example of two patients after transplantation of
      the kidney with pneumocystis pneumonia their experience with this disease.
      Predisposing factors include prolonged immunosuppression, protein and energy
      malnutrition, chronic inflammations and large doses of methylprednisolone. In the
      clinical picture dominated acute dyspnoea with hypoxaemia and non-productive
      cough. In one patient the X-ray picture was quite atypical. The prognosis of the
      disease is poor, both patients died.

PMID- 1394375
TI  - [Determination of antithrombin III in situ in the skin of patients with allergic
      arteriolitis].
AB  - The authors assessed antithrombin III in patients with allergic arteriolitis.
      Positive expression of antithrombin was assessed on endothelia, thrombi and
      infiltrate cells in approximately 2/3 of patients of the examined group (n = 23).
      The authors assume that expression of antithrombin III reflects inhibited
      hemocoagulation in the affected vessels as well as inhibition of leucocyte
      proteases in the above disease.

PMID- 1394376
TI  - [A case of recurrent alimentary lead poisoning].
AB  - The authors describe a case of lead poisoning in a family (father, mother, son,
      daughter). The condition was at first diagnosed as acute hepatic porphyria. The
      correct diagnosis was made on the basis of increased urinary excretion of delta
      aminolevulinic acid and coproporphyrin and on the basis of the revealed
      reversibly inhibited activity of delta-aminolevulinic acid dehydratase in red
      blood cells. The source of intoxication was the use of red lead pigment instead
      of dried red pepper.

PMID- 1394377
TI  - [The effect of chloroquine on lymphocytic HLA-A and B antigens].
AB  - The author investigated the effect of 20%, 15%, 10%, 5%, 2.5%, 1.25% chloroquine
      on HLA-A,B antigens on lymphocytes and on the reaction HLA-A,B antigen-antibody.
      HLA-A,B antigens are not released by chloroquine from the lymphocyte surface and
      their expressivity does not change, as was revealed by examination of the micro
      lymphocytotoxic and absorption test. Higher concentrations of chloroquine cause
      poly-reactivity of lymphocytes. A 20%, 15% and sometimes also 10% and 5% of
      chloroquine solution block the reaction HLA-A, B antigen--HLA antibodies. The
      reason for this is the destructive action of chloroquine on rabbit complement.

PMID- 1394378
TI  - [The second opinion--ethical and practical problems].

PMID- 1394379
TI  - [The beginnings of health care in the chemical industry in Ostrava].

PMID- 1394380
TI  - [Geriatrics in the United States].

PMID- 1394381
TI  - [Study on the interaction between hypertension, smoking and the disorder of
      lipids metabolism in the coronary artery disease].
AB  - The correlations of the coronary artery disease (CAD) and hypertension, smoking
      and/or the levels of lipoproteins and apolipoproteins, were studied in 100
      patients with CAD diagnosed by coronary arteriography and 141 non-CAD controls.
      The findings are: 1. There are: significant positive dose-response relationships
      between the degrees of CAD and the levels of diastolic pressure, cumulative
      smoking consumptions, the levels of high-density lipoprotein subclasses and
      apolipoproteins A1 and/or B. 2. The degrees of CAD in patients with the
      hypertension and smoking at same time were more serious than those with only a
      single risk factor. It's suggested that there are some synergy between
      hypertension and smoking in the occurrence of CAD. The synergic mechanism may be
      related to lipids metabolism.

PMID- 1394382
TI  - [Studies on the serotyping and pyocintyping of Pseudomonas aeruginosa].
AB  - Pseudomonas aeruginosa (118 strains) from Xian were typed by 12 groups O-serum
      and revised pyocin typing method Results indicated that VI, I, III were major
      serotypes, VI type were mainly from trauma infected, I type mainly from
      respiration system infected. Pyocintype were mainly I and UT types. Pyocintype I
      were mainly 1/c and 1/x subtypes. 85.7% of 1/c subtypes were serotype VI, 84.4%
      of 1/x subtypes were serotype I.

PMID- 1394383
TI  - [A study on EDTA antigens for detection of IgG antibodies to Legionella
      pneumophila].
AB  - The EDTA and Sonicate antigens used in ELISA for detection of IgG antibodies to
      Legionella Pneumophila serogroups 1-6 and Tatlock was evaluated. Sensitivity and
      specificity of EDTA antigens were compared with Sonicate antigens in three groups
      of subjects. In two serum samples from healthy employees, the Lp1 antibody titers
      with EDTA and Sonicate antigens were less than or equal to 1:160. Testing seven
      samples from patients indicated that four samples reacted with titers of 1:1280
      2560 to Lp1 with EDTA and Sonicate antigens. But in another three samples, the
      antibody titers to Lp1 with EDTA antigen were lower 1-3 dilution than Sonicate
      antigen. One of the lowest titer to EDTA was 1:320 that was interpreted as
      positive. In all of the seven samples, the antibody titers to Lp4 and Tatlock
      raised to 1:640-2560 with sonicate antigens and significantly higher than the
      titers with EDTA antigens (1:320-640). The comparison between the EDTA and
      Sonicate antigens showed that when the antibody titer with EDTA antigens greater
      than or equal to 1:320 was regarded as a positive mark the sensitivity of EDTA
      antigens was similar to Sonicate antigens and the specificity was better than
      Sonicate antigens. Comparison of EDTA antigen was simple. It is worth to further
      study.

PMID- 1394384
TI  - [Advances in sterilization].

PMID- 1394385
TI  - [Asymptomatic hepatitis B virus infection among the elderly].
AB  - The hepatitis B virus (HBV) infection usually occurs during infancy and children.
      To elucidate how the infection changes during the elderly life, 2233 residents
      were surveyed and among them 440 individuals with the age of 60-96 years were
      centered for analysis. The infection in the elderly was decreasing. HBsAg
      prevalence (5.0%) and titer (3.5 +/- 2.3) were getting lower, nearly all HBeAg
      seroconverted to anti-HBe, and the infection might be cleared at last. However,
      the HBV antibody prevalence steadily maintained, implying frequent HBV exposure
      and antibody responses during aging in the endemic area. Among them no fresh
      HBsAg were detected at one year follow-up, but antibodies developed in 10.8% of
      65 individuals without HBV markers initially, and more, in 79 with single anti
      HBs or anti-HBc 6.3% developed another antibody in a year. Therefore, the elderly
      population might be in a hypo-infection and dynamic hyperimmune status of the
      hepatitis B virus.

PMID- 1394386
TI  - [Serological study about the infection of hepatitis B in Xiyang County, Shanxi
      Province].
AB  - Authors examined HBsAg, anti-HBs and anti-HBc of 471 people in Xiyang, Shanxi.
      The positive rate is 10.19%, 34.61% and 19.11% respectively. The total infection
      rate of HBV is 52.65%. It indicates that Xiyang county is highly infectious area
      of HB. The age distribution of positive rate of HBsAg, anti-HBs, and the
      infection rate of HBV present special model: i.e. goes up along with age's
      growing, up to 30 years old, it gets the high peak. After 30 years old, the
      positive rate of HBsAg is going down along with the age's growing, the positive
      rate of anti-HBs and the infection rate of HBV go down a little. The group of 50
      years old has a high peak again. The positive rate of HBsAg of peasant is
      remarkable higher than cadre's. The infection rate of HBV of peasant is the
      highest, it is 59.55%. The infection rate of HBV of the people who work in food
      units is lowest, because they are examined regularly. The infection of man and
      woman is same.

PMID- 1394387
TI  - [Cause analysis of measles incidence in National Diseases Surveillance System in
      1990].
AB  - This paper described the time and areas distribution of 875 measles cases in DSP
      in 1990 and discussed relationship between vaccination and measles cases. Through
      studying cases in several points with high morbidity, the authors found that
      there was no high immunization coverage. It must have been the first chance of
      measles incidence. Further more the immunization technics and cold chain were
      found unqualified, which were thought to be the second chance.

PMID- 1394388
TI  - [Epidemic investigation of genital mycoplasma hominis infection in women].
AB  - The genital mycoplasma hominis infection in women was investigated at Xiaguan
      district, Nanjin in June, 1990. Leucorrheas from 722 women were tested with ELISA
      for the antigen of M. hominis. The prevalences of genital M. hominis were not
      statistically different among age and occupation groups. Women having pregnancy
      more than three times had a significantly higher infection rate, it is suggested
      that induced abortion might provide chances of the infection. The prevalence was
      significantly different among groups of various contraceptive means, it is lower
      in the group of contraceptive condom and higher in the group of intrauterine
      device.

PMID- 1394389
TI  - [Study of the effects of air pollution on human health in Beijing].
AB  - 3000 habitants from different polluted areas of Beijing were examined for their
      states of health in both the summer and the winter in 1989, and 7000
      questionnaires were filled. Meanwhile, the data of air pollution surveillance
      during 1980 and 1988 were collected and analysed. The air pollutants in the areas
      have been identified. The results of the study showed that the effects of air
      pollution on human health in urban were more severely than that in suburb and
      rural area; the complaints of respiratory system were correlative with the level
      of pollution in the areas; and the index method is useful in the studies of the
      effects of multi-factor pollution of human health.

PMID- 1394390
TI  - [Trend analysis of causes of death among the population in Shandong Province from
      1970 to 1974 and from 1981 to 1989].
AB  - This report showed the general mortality and changes of mortality distribution
      among the population in Shandong province in the early 1970S and in 1980S,
      through data analysis of causes of death in the Province from 1970 to 1974 and
      from 1981 to 1989. In the past 20 years, the mortality in respiratory diseases
      increased by 19.21%, ranking the first among the leading causes of death; the
      mortality in malignant tumors and cerebrovascular diseases increased by +7.15%
      and 75.31% respectively, rising from the third and fourth to the second and third
      leading causes of death, the mortality in heart diseases changed little,
      remaining in the fourth leading cause of death; the mortality in infectious
      diseases decreased by 78.22%, dropping from the second place in the early 1970S
      to the eighth place.

PMID- 1394391
TI  - [Influence of smoking on cholesterol concentrations in serum lipo-protein of
      healthy subjects].
AB  - Sixty hundred and nineteen-seven smokers and 841 non-smokers among healthy male
      workers of 40-60 years of age were comparatively observed. Their housing
      environment and working conditions were similar. The results showed that smoking
      had remarkable influence on the cholesterol concentration in the serum lipo
      protein of healthy subjects. The levels of HDL-C HDL2-C, HDL3-C and HDL2-C/HDL3-C
      of the smoking group were obviously lower than those of the non-smoking group,
      while the levels of LDL-C, VLDL-C and LDL-C/HDL-C of the smoking group were
      obviously higher than those of the non-smoking group. Moreover, these indices
      were significantly associated with the smoking amount, smoking duration, depth of
      inhalation. Smoking was an important dangerous factor for lowering levels of HDL
      C, HDL2-C, HDL 3-C, HDL2-C/HDL3-C and raising levels of LDL-C, VLDL-C, LDL-C/HDL
      C. The relative risk (RR) of the two factors were estimated to be 1.09-5.77 and
      2.37-3.57 respectively. The levels of the 7 indices such as HDL-C of passive
      smokers were identical with those of light smokers. This showed that passive
      smoking also had marked influence on cholesterol concentrations in serum
      lipoprotein.

PMID- 1394392
TI  - Empyema in children: a review of 52 cases.
AB  - A prospective study was undertaken to assess the clinical pattern, management and
      outcome in children admitted with empyema at Harare Hospital. Fifty-two children
      were seen and followed up during the three-year period, 1984-1987. All patients
      were managed with intrapleural drain and antibiotics. Two needed decortication.
      The predominant pathogen isolated from the pleural cavity was Staphylococcus
      aureus. All survived and on follow up only one child was found to have persistent
      radiological abnormality and poor exercise tolerance. Early intrapleural drainage
      and appropriate antibiotics should be the mainstay of treatment for empyema for
      the majority of children in Zimbabwe.

PMID- 1394393
TI  - Pattern of HIV-infection in Hurungwe district, Mashonaland West, Zimbabwe.
AB  - After the first case of HIV-infection had been diagnosed in 1986 in a Northern
      district of Zimbabwe, a local hospital based surveillance system, was introduced.
      In order to monitor the spread of the epidemic in the district, residence, age,
      sex and clinical presentation of all newly diagnosed HIV-patients were recorded.
      After three years, the data were compiled and analysed with the following
      results. Altogether 887 symptomatic HIV-patients (0.5 pc of the district
      population) were diagnosed. The most common HIV-associated signs and symptoms
      were PGL (47 pc), chest infection (29 pc), herpes zoster (24 pc) and chronic STDs
      (15 pc). The female-to-male ratio in adults was 1.4. The average age on diagnosis
      in women was 26.0 +/- 6.7 years and in men 30.7 +/- 8.6 years. The three years'
      cumulative incidence of HIV-cases was 27.2/1,000 in the urban area and 3/1,000 in
      the rural areas of the district.

PMID- 1394394
TI  - Bacterial contamination of food and household stored drinking water in a
      farmworker community in Zimbabwe.
AB  - Food and water samples, collected from the homes of farmworkers with children
      less than five years old, were cultured for Escherichia coli (which was used as
      an indicator of faecal contamination) and bacterial enteric pathogens. Sixteen
      percent of the food samples and 41 pc of the household stored water samples had
      E.coli. Ten percent of the foods had high E.coli counts greater than 10(4) counts
      per ml or g of food. Most of the foods were stored for more than 12 hours.
      Bacterial enteric pathogens were isolated in low percentages in foods and water
      except Aeromonas which was very common in household stored water. The majority of
      the faecally contaminated water samples had low E.coli counts (less than 20
      E.coli/100 ml) and 61 pc of the water was stored for less than 12 hours. There
      was no relationship between faecal contamination of the water and period of
      storage in the home. Household stored water had a higher percentage of samples
      contaminated with E.coli than the tap water which was used to fill the storage
      vessels. Household stored drinking water is a major route of transmission of
      Aeromonas in the rural community which was studied.

PMID- 1394395
TI  - Neurocysticercosis: experience with diagnosis by ELISA serology and computerised
      tomography in Zimbabwe.
AB  - Over a three-year period, 646 sera from 630 patients with signs and symptoms
      compatible with neurocysticercosis were investigated for antibodies to
      cysticercal antigens using an ELISA test. Overall, 12 pc specimens were positive.
      The sensitivity of the ELISA, when compared with a limited number of computerised
      tomography investigations, was over 70 pc. False negative serology was associated
      with HIV infection in some patients. The positive predictive value was 87 pc and
      the negative predictive value was 85 pc when patients with active infection,
      potentially amenable to chemotherapy, were considered. The specificity,
      determined from serological tests of patients with a variety of trematode,
      cestode and other infections, was over 90 pc. Three of 11 patients with
      intestinal taeniasis, and each of two patients with hydatid disease were
      seropositive. The results suggest the value of ELISA serology as a more cost
      effective diagnostic method for all patients with suspected cysticercosis.

PMID- 1394396
TI  - Penetrating abdominal spear injuries.
AB  - Eight cases of penetrating abdominal spear injuries are presented. The type and
      size of the spearhead as well as its direction and severity of the impact were
      reflected in the degree of visceral damage. At laparotomy, retro-peritoneal
      haematoma (RPH) was a constant finding. Morbi-mortality was associated with early
      haemorrhage or later septic complications. Manipulation of intra abdominal
      embedded spears may require unusual surgical procedures, and no attempt to
      extract the weapon should be made before emergency laparotomy is carried out.
      Prompt first aid and hospital referral, resuscitation and facilities for the
      treatment and care of the critically ill patient, were important factors
      influencing the outcome of these cases.

PMID- 1394397
TI  - Neonatal septicaemia in Calabar, Nigeria.
AB  - In a twelve-month prospective study of 132 neonates suspected of having
      septicaemia in the Special Care Babies Unit (SCBU) of the University of Calabar
      Teaching Hospital (UCTH), Calabar, 79 were confirmed by positive blood cultures.
      Forty (50.6 pc) of these were preterm infants. The incidence was 19.3 per 1,000
      hospital live births, while the mortality rate was 30.3 pc. The main predisposing
      factors were birth asphyxia, birth outside hospital, prolonged rupture of
      membranes, prolonged labour and poor water supply in hospital. The predominant
      pathogens were coliform organism and Staphylococcus aureus. The antibiotic
      sensitivity pattern of the pathogens suggest the use of gentamicin as a sole
      agent in the initial treatment of septicaemia while awaiting culture results. In
      view of the role of inadequate antenatal care, poor water supply and unhygienic
      delivery practices in the aetiology of newborn septicaemia, it is suggested that
      improved antenatal care, water supply and childbirth practices will reduce the
      incidence of septicaemia.

PMID- 1394398
TI  - Metastatic clostridial myonecrosis associated with intra-uterine clostridial
      infection: a report of three cases.
AB  - Three cases of metastatic Clostridial myonecrosis are reported, two following
      spontaneous and one following criminal abortion. This particular combination has
      not been reported before. The two survivors were managed by hysterectomy and
      disarticulation of the leg through the hip. The patient who died did so before
      surgery could be undertaken. The literature on gas gangrene infections of the
      uterus and metastatic Clostridial myonecrosis is reviewed and guidelines for
      management are discussed.

PMID- 1394399
TI  - Volvulus of the sigmoid colon in paediatric patients: report of two cases.
AB  - Two cases of volvulus of the sigmoid colon in paediatric patients are presented.
      The condition is rare in childhood. The diagnosis was established at laparotomy
      in the first case while the second case was diagnosed because of heightened
      awareness. The clinical features of the disease are essentially as in adults.

PMID- 1394400
TI  - Abnormal syndrome of iliac osteomyelitis presenting as acute appendicitis.
AB  - A case of right iliac osteomyelitis initially misdiagnosed and treated as acute
      appendicitis is reported. Deep-seated right lower quadrant pain persisted and a
      gluteal abscess appeared in the immediate post-operative period. The gluteal
      abscess was incised and it continued to discharge pus until appropriate diagnosis
      and treatment was instituted. Pain due to iliac osteomyelitis is deep-seated and
      may radiate to the thighs or lumbar region. Compression and distraction of the
      pelvis elicits pain in the affected ilium.

PMID- 1394401
TI  - The changing age ecology of measles and its implications on measles control.
AB  - In the City of Gweru measles vaccination was commenced in 1971. With the advent
      of the Expanded Programme on Immunisation in 1981-82, measles vaccination
      coverage was increased, reaching over 80 pc in 1985 and after. Despite this
      vaccination effort measles morbidity rates have remained high and epidemics
      continue to occur periodically. It is argued that the shift of the disease from
      young age groups to older children, coupled with the fact that there are more
      vaccinees amongst cases with the disease, will mean that transmission will
      continue uninterrupted. Possible reasons for persistent transmission in older
      children are explored. It is concluded that measles revaccination is required to
      interrupt measles transmission.

PMID- 1394402
TI  - Parental history of hypertension in Zimbabwe and cardiovascular reactivity to
      psychological experimental stress.
AB  - Thirty (16 male and 14 female) black subjects with a parental history of
      hypertension (FH) were matched in sex and age with 30 subjects without family
      history of hypertension (NFH). These two subgroups of black Zimbabweans were
      matched in number, sex and age and compared to FH and NFH subgroups of healthy,
      young white subjects. The relationship between parental history of hypertension
      and cardiovascular reactivity to alpha- and beta-adrenergic stressors was
      estimated by using cold pressure and mental stressor tests respectively. Black
      white differences in cardiovascular reactivity were found. Blacks at risk of
      getting hypertension showed greater vascular response to the cold pressor, which
      produces an alpha-adrenergic increase of vascular resistance, compared with the
      respective whites with parental history of hypertension who showed exaggerated
      reactivity to mental stressor, a beta-adrenergic activator that enhances
      cardiovascular reactivity via increases in cardiac output.

PMID- 1394403
TI  - Factual knowledge about AIDS and dating practices among high school students from
      selected schools.
AB  - Following various educational strategies by governmental and non-governmental
      organisations to educate youths and school teachers about HIV infection and
      prevention, this KABP survey was one attempt to evaluate the results. The study
      sample of 478 high school students was drawn from four randomly selected schools
      in Mashonaland and Matabeleland including high and low density, government and
      mission co-educational schools. The sample was randomly selected and stratified
      to represent sex and grade level. The KABP self administered questionnaire was
      used. The paper analyses the relationship between the knowledge and dating
      patterns. Generally, respondents demonstrated a 50pc to 80pc accuracy of factual
      knowledge. Of the 66pc Forms I through IV pupils who dated, 30pc preferred only
      sexually involved relationships and a small number considered the possibility of
      HIV/AIDS infection. A theoretically based tripartite coalition involving the
      school, the family health care services for education, guidance and support to
      promote responsible behaviour throughout childhood was suggested.

PMID- 1394405
TI  - Normal pulmonary function in Botswana.
AB  - Forced vital capacity, forced expiratory volume in one second and peak expiratory
      flow rate were measured in 125 adult Batswana who were without evidence of
      pulmonary disease. Regression co-efficients suitable for the calculation of
      normal values for these parameters are presented. Results are similar to those in
      other Negroid populations but lower than in Caucasian subjects.

PMID- 1394404
TI  - Socio-democratic characteristics of women presenting with abortion--a hospital
      based study.
AB  - OBJECTIVE: To determine socio-demographic characteristics and clinical features
      of women presenting with abortion, and to define factors associated with
      complications of abortion. DESIGN: A prospective descriptive study. SETTING:
      Women in Gynaecology casualty department at Harare Central Hospital, Harare,
      Zimbabwe. PATIENTS: 307 women with features of complete or incomplete abortion
      were interviewed during February to June 1991. They were randomly selected and
      represented 53pc of all women with the problem. RESULTS: Three quarters of the
      women were married and lived with their spouses. In 23.1pc this was a first
      pregnancy. Over a quarter of the women who were on the pill claimed to have
      fallen pregnant whilst on the pill, mainly because of poor compliance. One
      hundred and twenty-two were not on the pill but in only 16pc it was intended to
      fall pregnant. In nearly 30pc the pregnancy was not wanted but only 2.3pc
      admitted to having induced the abortion. Sepsis was present in 25.6pc and they
      tended to be younger, not presently married and have an unplanned pregnancy.
      Although there was some evidence of trauma in 6.2pc, it was not possible from the
      study to assess the percentage of abortion likely to have been induced.
      CONCLUSION: Contraceptive usage is generally low and cultural and traditional
      factors may play a role, but expanded sex education programmes and continued
      contraceptive counselling need reinforcing before attempts are made to review the
      legal issues regarding termination.

PMID- 1394406
TI  - The changing pattern of surgical pathology of the thyroid gland in Zambia.
AB  - Review of reports of thyroid tissue sent for histopathology to the Department of
      Pathology at the University Teaching Hospital, Lusaka (UTH) by one of the five
      general surgical units at the institution during the period January 1981-December
      1990 shows a 20pc decrease in the incidence of colloid goitre and doubling of the
      incidence of the adenoma and carcinoma when compared to the study done at the
      Central Hospital, Kitwe in the late sixties. In our study for the general
      pathology of the thyroid gland female to male ratio is 7.4:1; 1.25:1 when only
      thyroid cancers are considered. The incidence of papillary carcinoma is
      substantially lower than in the west. Recently, there has been an increased
      incidence of thyroid abscesses associated with HIV infection. Knowledge of the
      local pattern of surgical pathology of an organ is important for planning the
      operative management more effectively but in many developing countries, such as
      ours, this information is not readily available. Goitre is common in Zambia and
      to our knowledge to date there is only one comprehensive report done during the
      period January 1966, to March 1971. This deals with the Northern and Western
      regions of the country. This study was undertaken to look into the surgical
      pathology of the thyroid gland seen at the University Teaching Hospital, Lusaka,
      which is in the central part of the country.

PMID- 1394407
TI  - Lassa fever: review of virology, immunopathogenesis, and algorithms for control
      and therapy.
AB  - Lassa fever is an acute viral illness which causes consideration morbidity and
      mortality in the West African subregion. Recent studies have revealed that
      platelet and endothelial dysfunction might play a central role in the
      pathophysiology of this disease. Guidelines for the management of cases of the
      disease have recently been revised by the Centres for Disease Control,
      recommending care in local hospitals with use of meticulous barrier nursing
      techniques. This article reviews the epidemiology, immunology, pathogenesis and
      pathology, and current algorithms for prevention and therapy.

PMID- 1394408
TI  - Congenital absence of the internal carotid artery.
AB  - A case of a 27 year old male who was found to have the unusual congenital absence
      of one internal carotid artery is presented. A second case with similar but
      slightly different X-ray findings due to occlusion of the internal carotid is
      presented for comparison. Only forty cases of agenesis of the internal carotid
      artery have been found by us in the literature and this appears to be the first
      from Africa.

PMID- 1394409
TI  - Repeat balloon aortic valvuloplasty.
AB  - This paper attempts to determine limitations and indications of performing a
      second balloon aortic valvuloplasty procedure (BAV2) because of restenosis, which
      is the major limitation of this technique. From September 1985 to December 1989,
      357 patients underwent a primary BAV (BAV1) and 67 patients had a BAV2. Forty-two
      patients (group A) had repeat catheterization because they were markedly
      symptomatic 11 +/- 7 months after BAV1. Twenty-five patients (group B) came from
      a group of 73 patients who had been systematically scheduled for repeat
      catheterization in order to evaluate the hemodynamic restenosis rate 8 +/- 3
      months after BAV. At time of BAV2 most of the patients of group A were severely
      disabled. Comparison of pre-BAV2 gradient and aortic valve area with pre-BAV1
      measurements showed in a slightly less severe degree of aortic stenosis in group
      A and in group B with any difference in cardiac index and ejection fraction.
      Immediately following BAV2, the gradient decreased from 72 +/- 22 to 33 +/- 15 mm
      Hg (P less than 0.001) and aortic valve area increased from 0.56 +/- 0.18 to 0.85
      +/- 0.28 cm2 (p less than 0.001) in group A. In group B, gradient decreased from
      68 +/- 15 to 33 +/- 15 mm Hg (p less than 0.001) and aortic valve area increased
      from 0.70 +/- 0.16 to 0.90 +/- 0.25 cm2 (p less than 0.001).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1394410
TI  - Use of twenty-four hour infusions of intracoronary tissue plasminogen activator
      to increase the application of coronary angioplasty.
AB  - Coronary arteries occluded by long lengths of thrombus are usually considered
      unattractive for angioplasty. Nine patients (8 male, mean age 50.1 years)
      undergoing angiography for unstable angina were found to have single vessel
      disease considered unsuitable for angioplasty as the vessel was occluded by a
      long length of thrombus. These patients were treated with 24 hr intracoronary
      infusions of 100 mg tPA in an attempt to make angioplasty feasible. Marked
      thrombolysis occurred in 7 patients who received uncomplicated infusions. One
      case was unsuccessful due to catheter displacement, while another had the
      infusion ceased due to an intracerebral bleed from a previously silent A-V
      malformation. This was the only major complication. Angioplasty was attempted in
      6 of 7 cases where lysis had been achieved, with success in all lesions
      attempted. This reports shows that intracoronary tPA infused over prolonged
      periods produces excellent thrombolysis, making angioplasty feasible in some
      patients who were previously unsuitable.

PMID- 1394411
TI  - Activated clotting times and activated partial thromboplastin times in patients
      undergoing coronary angioplasty who receive bolus doses of heparin.
AB  - The accurate assessment of coagulation status is an important part of
      interventional procedures performed in the cardiac catheterization laboratory.
      While the traditional clinical means of assessing heparin anticoagulation has
      been with the activated partial thromboplastin time (APTT), the activated
      coagulation time (ACT) has come into widespread use in the catheterization
      laboratory as an assay of whole blood clotting time which can be performed
      rapidly at the bedside. The purpose of the present study was to (1) assess the
      anticoagulant effect of a 10,000 U bolus of heparin in PTCA patients and (2)
      document the relationship between ACTs and APTTs in a subset of these patients.
      Baseline and postheparin ACTs were measured using a HemoTec coagulation timer in
      545 unselected PTCA patients. The average baseline ACT was 120 +/- 22 sec. After
      a 10,000 U bolus of heparin the average ACT was 249 +/- 44 sec; 58% of patients
      had an ACT less than 250 sec, 17% had an ACT between 250 and 275 sec, 12% had an
      ACT between 275 and 300 sec, and 13% had an ACT greater than 300 sec. A total of
      175 paired ACT and APTT measurements were obtained in a random subset of these
      patients at baseline, after heparinization, and at 4-6 hr intervals after the
      procedure. The APTT was limited by absolute upper and lower limits of 150 and 22
      sec; there were no such limits on the ACT. When limiting values were excluded,
      there was a strong overall correlation between ACT and APTT measurements (r =
      0.92, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394412
TI  - Transseptal catheterization 1992: it is here to stay.

PMID- 1394413
TI  - Transseptal catheterization update 1992.
AB  - Resurgence of the transseptal procedure in the last decade has occurred
      coincident with the advent of therapeutic catheterizations and in particular
      mitral balloon vavuloplasty. As larger numbers of these procedures have been
      performed, experience shows that the position of intended septal puncture varies
      for each anticipated procedure and need not lie at the fossa ovalis, which is
      frequently displaced or inaccessible. Recognizing the dynamic alterations in
      septal and atrial anatomy that accompany the various combinations of valvular
      heart disease, the experienced interventionalist will use precatheterization echo
      and radiological techniques to enable precise and localized transseptal puncture.
      Using these techniques in 597 patients for valvular heart disease, we have had no
      deaths and a morbidity of 1.8% with the transseptal puncture.

PMID- 1394414
TI  - Atrial septal puncture technique in percutaneous transvenous mitral
      commissurotomy: mitral valvuloplasty using the Inoue balloon catheter technique.
AB  - Transseptal catheterization is a vital component of percutaneous transvenous
      mitral commissurotomy. Therefore, a well-executed transseptal catheterization is
      the key to a safe and successful percutaneous transvenous mitral commissurotomy.
      Two major problems inherent in atrial septal puncture for percutaneous
      transvenous mitral commissurotomy are cardiac perforation and puncture of an
      inappropriate atrial septal site. The former may lead to serious complication of
      cardiac tamponade and the latter to possible difficulty in maneuvering the Inoue
      balloon catheter across the mitral orifice. This article details atrial septal
      puncture technique, including landmark selection for optimal septal puncture
      sites, avoidance of inappropriate puncture sites, and step-by-step description of
      atrial septal puncture.

PMID- 1394415
TI  - Excimer laser coronary angioplasty for failed PTCA.
AB  - Specific indications for excimer laser coronary angioplasty (ELCA) are yet
      undefined. We report two specific applications of ELCA when percutaneous
      transluminal coronary angioplasty (PTCA) failed: (1) to facilitate balloon
      crossing a long rigid stenosis that could not be crossed after the lesion was
      wired, and (2) to overcome prominent elastic recoil of the stenosis after PTCA.

PMID- 1394416
TI  - Prolonged intravenous urokinase infusion: an alternative pharmacologic approach
      in the treatment of thrombus-containing saphenous vein graft stenoses.
AB  - A subtotally occlusive saphenous vein graft stenosis resolved after rapid
      intracoronary and prolonged intravenous urokinase infusion. Additional therapy
      was unnecessary, avoiding the attendant risks of saphenous vein graft
      angioplasty. Combined intracoronary and intravenous urokinase infusion should be
      considered prior to coronary angioplasty of saphenous vein graft stenoses,
      particularly when diffuse degeneration is present or the risk of underlying
      thrombus is high.

PMID- 1394417
TI  - New approach to management of intraaortic balloon pumps in patients with
      peripheral vascular disease: case reports of four patients requiring urgent IABP
      insertion.
AB  - Four selected cases of emergent IABP insertion in PV patients are presented.
      After angiographic documentation of critical iliac stenosis, conservative
      peripheral angioplasty was performed prior to IABP insertion. No patient
      experienced a peripheral ischemic event associated with IABP use.

PMID- 1394419
TI  - Pseudoaneurysm of coronary artery following rupture of coronary artery during
      coronary angioplasty.
AB  - Rupture of the coronary artery is a rare complication of percutaneous
      transluminal coronary angioplasty (PTCA). We describe a case of coronary artery
      rupture during PTCA resulting in the formation of a coronary artery
      pseudoaneurysm. The pseudoaneurysm was successfully treated by percutaneous
      spring-coil embolization of the coronary artery.

PMID- 1394418
TI  - Antegrade selective coronary angiography via the transseptal approach in a
      patient with severe vascular disease.
AB  - We describe a case of a woman with severe vascular disease in whom retrograde
      access to the aortic root was limited by both aortoiliac and axillary disease.
      Transseptal catheterization was performed in anticipation of percutaneous aortic
      valvuloplasty. Selective antegrade angiography was successfully performed using
      catheters introduced through the transseptal sheath.

PMID- 1394420
TI  - Interpretation of cardiac pathophysiology from pressure waveform analysis: mitral
      valve gradients: Part I.
AB  - The mitral valve gradient is dependent on the precise measurement of left atrial
      (or pulmonary capillary wedge) and left ventricular pressures. Artifacts
      involving either pressure measurement will produce inaccuracies which may have
      clinical significance. Several methods and formulas using both invasive and
      noninvasive techniques should verify clinical findings and confirm the severity
      of mitral valve disease prior to definite therapy. The changes in mitral valve
      gradients after balloon catheter valvuloplasty will be discussed in part II of
      this hemodynamic rounds.

PMID- 1394421
TI  - Modified Inoue technique for difficult mitral balloon commissurotomy.

PMID- 1394422
TI  - Percutaneous vascular hemostasis device for interventional procedures.
AB  - A new 11.5F over-the-wire vascular hemostasis device was compared to conventional
      manual compression in normal swine femoral arteries. Using percutaneous
      techniques, the collagen was deposited and hemostasis achieved in 7 vessels after
      1 minute total, plus 4 minutes partial compression, while control manual
      compression required more than 5 minutes total compression to avoid hematoma
      formation. One month follow-up of treated arteries (n = 4) and controls (n = 3)
      showed no impairment in distal pulse or differences in histology at the puncture
      site in the control and treated arteries. Thus, the vascular hemostasis device
      technique is safe and effective, achieves hemostasis with less compression time
      and complications, and does not interfere with arterial wall healing or
      compromise the lumen.

PMID- 1394423
TI  - Inoue balloon usefulness in case of failure to stabilize bifoil catheter balloons
      during percutaneous mitral valvotomy.
AB  - A new bifoil balloon catheter has been used in the last 120 percutaneous mitral
      valvotomies carried out in our institution. The shaft segment between the two
      balloons of the bifoil catheter has been adjusted to the guide-wire diameter,
      allowing its introduction through a 14F sheath. This thinner shaft does not
      always offer enough back up to the balloons during inflation. An Inoue balloon
      replaced an unstable bifoil balloon in 5 cases of mitral dilatation failure due
      to balloon instability, regularly providing firm stability until full balloon
      inflation.

PMID- 1394424
TI  - Rotational vs. directional atherectomy.

PMID- 1394425
TI  - Femoral artery puncture.

PMID- 1394426
TI  - The structure of human mitochondrial manganese superoxide dismutase reveals a
      novel tetrameric interface of two 4-helix bundles.
AB  - The 2.2 A resolution crystal structure of recombinant human manganese superoxide
      dismutase, a homotetrameric enzyme that protects mitochondria against oxygen
      mediated free radical damage, has been determined. Within each subunit, both the
      N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands
      to the catalytic manganese site. Two identical 4-helix bundles, symmetrically
      assembled from the N-terminal helical hairpins, form novel tetrameric interfaces
      that stabilize the active sites. Structurally altered polymorphic variants with
      reduced activity, such as tetrameric interface mutant Ile-58 to Thr, may produce
      not only an early selective advantage, through enhanced cytotoxicity of tumor
      necrosis factor for virus-infected cells, but also detrimental effects from
      increased mitochondrial oxidative damage, contributing to degenerative
      conditions, including diabetes, aging, and Parkinson's and Alzheimer's diseases.

PMID- 1394427
TI  - A nucleosome core is transferred out of the path of a transcribing polymerase.
AB  - We have determined the fate of a nucleosome core on transcription. A nucleosome
      core was assembled on a short DNA fragment and ligated into a plasmid containing
      a promoter and terminators for SP6 RNA polymerase. The nucleosome core was stable
      in the absence of transcription. The distribution of nucleosome cores after
      transcription was examined. The histone octamer was displaced from its original
      site and reformed a nucleosome core at a new site within the same plasmid
      molecule, with some preference for the untranscribed region behind the promoter.
      These observations eliminate several models that have been proposed for
      transcription through a nucleosome core. Our results suggest that a nucleosome
      core in the path of a transcribing polymerase is displaced by transfer to the
      closest acceptor DNA.

PMID- 1394428
TI  - A soluble receptor for interleukin-1 beta encoded by vaccinia virus: a novel
      mechanism of virus modulation of the host response to infection.
AB  - Vaccinia virus gene B15R is shown to encode an abundant, secretory glycoprotein
      that functions as a soluble interleukin-1 (IL-1) receptor. This IL-1 receptor has
      novel specificity since, in contrast with cellular counterparts, it binds only IL
      1 beta and not IL-1 alpha or the natural competitor IL-1 receptor antagonist. The
      vaccinia IL-1 beta receptor is secreted when expressed in a baculovirus system
      and competitively inhibited binding of IL-1 beta to the natural receptor on T
      cells. Deletion of B15R from vaccinia virus accelerated the appearance of
      symptoms of illness and mortality in intranasally infected mice, suggesting that
      the blockade of IL-1 beta by vaccinia virus can diminish the systemic acute phase
      response to infection and modulate the severity of the disease. The IL-1 beta
      binding activity is present in other orthopoxviruses.

PMID- 1394429
TI  - Molecular basis of human hypertension: role of angiotensinogen.
AB  - Essential hypertension is a common human disease believed to result from the
      interplay of multiple genetic and environmental determinants. In genetic studies
      of two large panels of hypertensive sibships from widely separated geographical
      areas, we obtained evidence of genetic linkage between the angiotensinogen gene
      (AGT) and hypertension, demonstrated association of AGT molecular variants with
      the disease, and found significant differences in plasma concentrations of
      angiotensinogen among hypertensive subjects with different AGT genotypes. The
      corroboration and replication afforded by these results support the
      interpretation that molecular variants of AGT constitute inherited
      predispositions to essential hypertension in humans.

PMID- 1394430
TI  - Secretion and localized transcription suggest a role in positional signaling for
      products of the segmentation gene hedgehog.
AB  - The segment polarity genes engrailed and wingless are expressed in neighboring
      stripes of cells on opposite sides of the Drosophila parasegment boundary. Each
      gene is mutually required for maintenance of the other's expression; continued
      expression of both also requires several other segment polarity genes. We show
      here that one such gene, hedgehog, encodes a protein targeted to the secretory
      pathway and is expressed coincidently with engrailed in embryos and in imaginal
      discs; maintenance of the hedgehog expression pattern is itself dependent upon
      other segment polarity genes including engrailed and wingless. Expression of
      hedgehog thus functions in, and is sensitive to, positional signaling. These
      properties are consistent with the non-cell autonomous requirement for hedgehog
      in cuticular patterning and in maintenance of wingless expression.

PMID- 1394431
TI  - Virus proteins that counteract host immune defenses.

PMID- 1394432
TI  - slow border cells, a locus required for a developmentally regulated cell
      migration during oogenesis, encodes Drosophila C/EBP.
AB  - During Drosophila oogenesis six to ten follicle cells, the border cells, undergo
      a dramatic and stereotypic migration through the developing egg chamber. We
      identified four independent P element insertion mutations that specifically
      blocked border cell migration. They defined a single, novel locus that was named
      slow border cells (slbo), because hypomorphic alleles caused delayed onset of the
      migration. Laser ablation of the border cells, or failure of their migration,
      caused improper morphogenesis of the micropyle, the egg-shell structure through
      which the sperm enters at fertilization. The slbo locus was found to encode a
      product homologous to the CCAAT/enhancer-binding protein (C/EBP), a basic region
      leucine zipper transcription factor. Drosophila C/EBP may be required for the
      expression of gene products mediating border cell migration.

PMID- 1394433
TI  - Bidirectional movement of a nascent polypeptide across microsomal membranes
      reveals requirements for vectorial translocation of proteins.
AB  - The translocation of polypeptides across the endoplasmic reticulum is a vectorial
      process that occurs probably through a protein channel by a mechanism as yet
      undetermined. Here, we demonstrate bidirectional movement of a 221 residue
      nascent polypeptide across microsomal membranes and provide evidence suggesting
      that the retrograde movement is through the translocation channel. Retrograde
      movement is observed only when the polypeptide is generated from a truncated
      transcript; addition of a stop codon after codon 221 confers vectorial movement.
      Retrograde movement can also be prevented by glycosylation of the nascent
      polypeptide, as well as by inclusion of 32 additional amino acids that may
      promote folding of the translocated chain. We propose that the protein
      translocation channel is a passive pore that does not create a directional bias
      in polypeptide movement and that vectorial translocation is driven by nascent
      chain elongation and sustained by posttranslocation events that prevent
      retrograde movement.

PMID- 1394435
TI  - Effects of glutathione on the synthesis and turnover of interleukin-2 receptors.
AB  - Internalization of IL-2 is important for its biological activities. The
      internalization of IL-2 was regulated by the duration of glutathione (GSH)
      treatment in CTLL-2 and CT-4R cells. Flow cytometric studies showed that the
      level of surface IL-2 receptors was not increased by GSH treatment. Northern blot
      analysis showed that the mRNA of IL-2Rp55 and IL-2Rp70, the two major components
      of the high-affinity IL-2 receptors, was increased 6 hr after GSH treatment. The
      appearance rate of membrane IL-2 receptors in GSH-treated cells was faster than
      that of the untreated cells. GSH also shortened the half-life (from 5 to less
      than or equal to 3 hr) and thus increased the turnover of the surface high
      affinity IL-2 receptors. These results suggest that although GSH does not affect
      the level of surface IL-2 receptors, GSH may regulate the internalization of IL-2
      by enhancing the synthesis and turnover of surface IL-2 receptors.

PMID- 1394434
TI  - The translation machinery and 70 kd heat shock protein cooperate in protein
      synthesis.
AB  - The function of the yeast SSB 70 kd heatshock proteins (hsp70s) was investigated
      by a variety of approaches. The SSB hsp70s (Ssb1/2p) are associated with
      translating ribosomes. This association is disrupted by puromycin, suggesting
      that Ssb1/2p may bind directly to the nascent polypeptide. Mutant ssb1 ssb2
      strains grow slowly, contain a low number of translating ribosomes, and are
      hypersensitive to several inhibitors of protein synthesis. The slow growth
      phenotype of ssb1 ssb2 mutants is suppressed by increased copy number of a gene
      encoding a novel translation elongation factor 1 alpha (EF-1 alpha)-like protein.
      We suggest that cytosolic hsp70 aids in the passage of the nascent polypeptide
      chain through the ribosome in a manner analogous to the role played by organelle
      localized hsp70 in the transport of proteins across membranes.

PMID- 1394436
TI  - Agonistic effects of tyrphostins on human peripheral mononuclear cells.
AB  - Tyrosine kinases of the src family, p56lck and p59fyn, were implicated in the
      transduction of signals via the T-cell receptor complex. These kinases are
      negatively regulated by phosphorylation of a carboxyl-terminal tyrosine residue.
      Tyrphostins are synthetic low molecular weight compounds that selectively inhibit
      different protein tyrosine kinases. We report here on the agonistic and
      antagonistic effects of tyrphostins on human peripheral blood mononuclear cells
      (PBM). At low concentration, the tyrphostins enhanced glucose uptake and maximal
      stimulation was attained at a concentration characteristic for each of the
      tyrphostins used. Higher concentrations were less effective. The tyrphostins
      AG126 and AG183 were also found to enhance IL-2-induced cytotoxicity in human PBM
      in a biphasic manner. In contrast, the tyrphostin AG17 markedly inhibited IL-2
      induced cytotoxicity at low AG17 concentration and no stimulation was observed.
      The tyrphostins tested had selective effects on [3H]thymidine incorporation
      induced by the mixed lymphocyte culture and different agents. The most potent
      inhibitor was AG17. Tyrphostins also affect cytokine secretion by human PBM.
      AG126 and AG183 enhanced TNF-alpha secretion and this effect was more prominent
      in the presence of IL-2. AG126 enhanced IFN-gamma, IL-1, and IL-6 production in
      PBM that were costimulated with the stress stimuli heat shock and phenylarsine
      oxide. The stimulatory effects of the tyrphostins on cytokine secretion and
      induction of cytotoxicity might be interrelated. The agonistic and antagonistic
      effects of tyrphostins on lymphocyte functions may have therapeutic potential.

PMID- 1394437
TI  - Estrogen accelerates immune complex glomerulonephritis but ameliorates T cell
      mediated vasculitis and sialadenitis in autoimmune MRL lpr/lpr mice.
AB  - Estrogen is known to influence immune responses in healthy subjects in a
      dichotomous fashion. Thus, in number of previous studies we and others have
      demonstrated that B cell activities are augmented after exposure to estrogen
      whereas T cell reactivity is suppressed. Furthermore, it has been shown that this
      hormone has significant impact on the course of certain human and experimental
      autoimmune diseases. In this study we report that treatment with physiological
      doses of estradiol exerts dichotomous effects on different manifestations of the
      lupus disease in MRL/l mice. On one hand immune complex-mediated
      glomerulonephritis was significantly accelerated. This outcome was due to
      polyclonal B cell activation with increased production of antibodies to double
      stranded DNA and formation of circulating immune complexes. In contrast, T cell
      mediated lesions such as focal sialadenitis, renal vasculitis, and periarticular
      inflammation were all significantly ameliorated in MRL/l mice exposed to
      estrogen. Thus, we were able to demonstrate that, within one subject and even
      within one organ, administration of estrogen leads to differential outcome of SLE
      morbidity. We propose that the differential effect of estrogen on the
      manifestations of the autoimmune disease of MRL/l mice is due to its dichotomous
      effects on B and T cell-mediated immune responses.

PMID- 1394438
TI  - The involvement of protein kinase C in activation-induced cell death in T-cell
      hybridoma.
AB  - T-cell hybridoma activated by a variety of stimuli such as anti-cell surface
      antigen, notably CD3 and T-cell receptors, and Con A undergoes a cell lysis
      process called activation-induced cell death (AICD). It was found that the major
      protein kinase C (PKC) isoform in the 2B4.11 T-cell hybridoma, PKC(alpha), was
      translocated from the cytosolic to the particulate fraction when these hybridoma
      cells were induced to die by plastic-adsorbed anti-CD3 antibodies. Inhibitors of
      protein phosphorylation rescued 2B4.11 cells from AICD as determined by the
      analysis of cellular metabolism and the proportion of living cells. Furthermore,
      PKC(alpha) down-regulation by phorbol ester treatment abolished AICD, and the
      degree of PKC down-regulation correlated well with the degree of AICD
      abolishment, suggesting that PKC activation represents an essential step in the
      molecular mechanisms underlying AICD in this T-cell hybridoma.

PMID- 1394439
TI  - Mixed interleukins and thymosin fraction V synergistically induce T lymphocyte
      development in hydrocortisone-treated aged mice.
AB  - Analysis of the role of interleukins in T cell ontogeny in vitro indicates that
      the regulation of T cell development involves interleukins (ILs) as well as
      thymic hormones (THs). In order to assess their respective roles in T lymphocyte
      development in vivo, chemically thymectomized mice were treated with ILs and THs.
      After 2 days of hydrocortisone treatment, aged mice showed acute thymic
      involution (weight was less than 30% of control) and reduced spleen size (less
      than 80% of control) with progressive recovery to 8 days. After 2 days of
      hydrocortisone treatment, adult mice were injected for 5 days with mixed buffy
      coat interleukins (BC-IL; 50 units IL2 equivalence), purified IL2 (50 units),
      rIL1 beta (4 ng), and thymosin fraction V (TF5; 100 micrograms). The animals were
      sacrificed and spleens and thymuses were analyzed for weight, cellularity, T cell
      number, subsets, and function as determined by proliferative responses to
      concanavalin A and ILs. BC-IL treatment increased the recovery of spleen and
      thymus weights and cellularity with corresponding augmentation of number and
      function of T lymphocytes; neither IL1 or IL2 or their combination had this
      effect. TF5 had no effect alone but strongly potentiated the effect of BC-IL on T
      lymphocyte function. These data indicate that BC-IL in combination with thymic
      peptides potently promotes T lymphocyte development. The combination may be
      therapeutically relevant for immunorestoration.

PMID- 1394440
TI  - Treatment of fetal thymic organ culture with IL-1 leads to accelerated
      differentiation of subsets of CD4-CD8- cells.
AB  - Using fetal thymic organ culture (FTOC), we describe the effects of IL-1 on T
      cell differentiation, particularly within the CD4-CD8- subset. While treatment of
      FTOC with IL-1 led to a modest reduction in total thymocyte yield, it induced an
      increase in the percentage of CD4-CD8- cells that express IL-2R early in culture
      and a decrease in the number of their precursors (CD44+IL-2R- cells). The
      increase in the percentage of cells expressing IL-2R was not accompanied by an
      increase in the number of these cells. At later time points these IL-2R+ cells
      (and their precursors) were reduced relative to controls. The total number of CD4
      CD8-CD3- precursor cells in IL-1-treated cultures was reduced to approximately
      half that in controls at Day 12 of culture. However, only minor inhibition of
      total cell number was observed, which, taken together with the greater frequency
      of IL-2R+ precursors, suggests that this depletion of the pool of precursors may
      have been due to the induction of premature differentiation rather than to its
      inhibition.

PMID- 1394441
TI  - Suppression of interleukin-2 and interleukin-2 receptor expression in Jurkat
      cells stably expressing the human immunodeficiency virus Tat protein.
AB  - The Jurkat T cell line was stably transfected with an Epstein-Barr virus-based
      episomal replicon designed to express high levels of the HIV-1 Tat protein. After
      selection in hygromycin B, high-level Tat activity was detected in 3 of 18
      transfected cell lines. After stimulation with phytohemagglutinin (PHA) and
      phorbol myristate acetate (PMA), Tat transfectants with high Tat expression
      showed diminished expression of interleukin-2 (IL-2) and the interleukin-2
      receptor alpha chain (IL-2R) when compared to untransfected Jurkat cells or
      Jurkat cell lines transfected with the parent control plasmid. Sublines derived
      from the high-level Tat transfectants with reduced Tat activity showed
      normalization of PHA/PMA-induced IL-2 expression. Northern analysis showed
      diminished expression of IL-2 and IL-2R mRNA in the stimulated Tat transfectants.
      Inhibition of IL-2 and IL-2R expression by the HIV-1 Tat protein may contribute
      to the immune suppression that characterizes HIV-1 infection.

PMID- 1394442
TI  - Inhibition of in vitro T cell activation by corneal endothelial cells.
AB  - Cells and tissues of the anterior uvea and aqueous humor express activities which
      inhibit immune responses. These activities include soluble factors such as TGF
      beta and uncharacterized cell surface interactions. Relatively little is known
      regarding the immunologic activities of corneal endothelium, despite its
      potentially important role in contributing to the immune privilege of the
      anterior chamber and the high success rate of corneal transplantation. In this
      report, in vitro studies of cultured rat corneal endothelial (CE) cells were done
      using S-antigen-specific LEW rat T cell lines, or S-antigen-specific T cell
      hybridomas, to examine the immunologic capabilities of CE cells. Monolayers of
      LEW rat CE cells were unable to present antigen or a mitogen, Con A, to T cell
      lines or hybridomas as assessed by the lack of a proliferative response or IL-2
      secretion. Furthermore, the CE cells exerted a potent inhibitory effect when
      added to in vitro proliferation assays of T cell lines stimulated with antigen or
      Con A. When T cells were preactivated on conventional antigen presenting cells
      and then transferred to wells containing CE cells, their proliferation was not
      inhibited. Although CE cells inhibited activation of T cell lines and hybridomas,
      they did not inhibit the growth of T cell hybridomas or CTLL cells, nor did the
      CE cells adversely affect the viability of resting T cells cultured on CE
      monolayers. The inhibitory effect was reversible as preincubation of T cells on
      CE cells for up to 6 days followed by washes restored T cell responsiveness when
      assayed on splenocytes. The inability to stimulate proliferative responses was
      not affected by preincubation of the CE cells with lymphokines which increase MHC
      antigen expression. The inhibition observed in these assays was not MHC
      restricted as CE cells from both LEW and BN rats were equally inhibitory. CE
      cells from rabbits and cats were also potent inhibitors of T cell activation,
      suggesting that the mechanism is evolutionarily conserved. The mechanism of
      inhibition of CE cells is unknown at this time.

PMID- 1394443
TI  - Sensitization of rat alveolar macrophages to enhanced TNF-alpha release by in
      vivo treatment with dexamethasone.
AB  - Treatment of rats with dexamethasone rapidly induced a marked weight loss which
      occurred within 3 days and persisted for several weeks. The cachectic state was
      paralleled by increased serum levels of triglycerides, albumin, and protein and a
      strong reduction of blood mononuclear leukocytes. In lung sections, an increased
      number of mononuclear giant cells was found but no bacteria, fungi, or
      Pneumocystis carinii organisms. Quite strikingly, alveolar macrophages from
      dexamethasone-treated rats, but not from control animals, were highly sensitive
      to LPS and released large amounts of TNF-alpha ex vivo. Also under in vivo
      conditions, high TNF-alpha serum concentrations were found in dexamethasone
      treated but not control rats when examined 1 1/2 hr after an intravenous LPS
      injection. These data suggest that the glucocorticoid-induced cachexia of rats
      may be linked, at least in part, to readily inducible TNF-alpha release from
      primed macrophages.

PMID- 1394444
TI  - Specific T-cell factor production and lymphocytes in the direct surroundings of a
      subcutaneous allogeneic tumor.
AB  - Antigen-specific T-cell factors (TCF) play a role in the initiation of cellular
      immune responses. In allogeneic mouse-tumor models lymphocytes from the direct
      tumor surroundings of both euthymic and nude mice produce TCF. These lymphocytes
      produce TCF when collected already 1 day after subcutaneous (sc) injection of
      tumor cells. In contrast to euthymic mice, draining lymph nodes and spleen of
      nude mice did not contain TCF-producing lymphocytes at any stage after sc tumor
      cell injection. In sensitized euthymic mice TCF production by lymphocytes is
      significantly higher in the direct tumor surroundings than in draining lymph
      nodes or spleen. At 2 and 5 days after tumor cell injection, the mononuclear cell
      infiltrate of the tissue surrounding the tumor in euthymic mice showed low
      expression of Thy 1, CD3, TCR alpha beta, TCR gamma delta, CD4, CD8, and asialo
      GM1, whereas several lymphocytes and mast cells were positive for monoclonal
      antibody (mAb) 14-30 (directed against TCF). In both euthymic and nude mice, sc
      injected tumor cells showed apoptosis. In conclusion, the direct tumor
      surroundings are the first (and, for nude mice, the only) site of TCF production,
      sc injection of tumor cells attracts mAb 14-30-positive lymphocytes and renders
      mast cells positive for mAb 14-30.

PMID- 1394445
TI  - Effect of immunosuppressive therapy on cytolytic activity of immunodeficient
      mice: implications for xenogeneic transplantation.
AB  - Despite major deficits in their immune system, SCID, Nude, and NIH III mice
      reject allo- and xenografts, particularly leukemic cell lines, albeit less
      readily than immunologically intact mice. Since variation among these
      immunodeficient mouse strains in rejection of a human lymphoid cell line (CCRF
      CEM) parallels splenic non-MHC-mediated cytolytic activity, non-MHC-restricted
      cytolytic activity may be responsible for retained resistance to leukemic cell
      transplantation. SCID mice that had the least cytolytic activity accepted 100% of
      their grafts. The converse was true for NIH III mice that showed the greatest
      cytolytic activity and were relatively resistant to CEM cell engraftment.
      Different approaches to ablate NK activity and thus enhance engraftment led to
      variable results for each strain. A single dose (500 micrograms) of anti
      asialoGM1 (AsGM1) markedly reduced NK activity in SCID and NIH III mice by 60 and
      40%, respectively. A moderate 20% decrease was seen in Nude mice at this dose. In
      contrast, gamma irradiation suppressed NK activity by greater than 80% of
      baseline levels in all three strains. Of importance, total cytolytic activity in
      immunosuppressed Nude and NIH III mice, although significantly depressed compared
      to untreated mice of the same strain, still remained higher than that seen in
      nonimmunosuppressed SCID mice. Enhanced engraftment and systemic dissemination of
      CEM cells in immunosuppressed mice correlated directly with decreased total
      splenic cytolytic activity in all three strains. These results have implications
      for the use of immunodeficient models for transplantation, tumor immunobiology,
      and engraftment of a human immune system.

PMID- 1394446
TI  - A study of autologous anti-idiotypic antibody-forming cells in mice of different
      ages and genetic backgrounds.
AB  - Antibody response to phosphorylcholine, an immunodominant epitope of
      Streptococcus pneumoniae R36a (Pn), is characterized by a public idiotype, T15,
      that is expressed on a large proportion of antibody molecules produced by all
      mouse inbred strains. The ability of the immune system to produce an autologous
      antibody to T15 upon immunization with Pn vaccine was investigated using a
      modified ELISA plaque assay for detection of single antibody-forming cells (AFC).
      The limit of ELISA assay for detection of specific anti-T15 AFC is approximately
      300 cells/spleen. However, our studies failed to detect any autologous anti-T15
      AFC in the course of the primary antibody response to Pn vaccine in young/adult
      (2-4 months) BALB/c and C57BL/6 mice. Aged mice (20-22 months) also failed to
      develop any specific auto-anti-T15 AFC upon the primary Pn immunization, despite
      the fact that the anti-Pn response in these animals changes both quantitatively
      and qualitatively. In order to generate specific anti-T15 AFC, BALB/c mice had to
      be immunized repeatedly with Pn vaccine (four weekly injections) or immunized
      directly with T15 protein in CFA. Different results were obtained with D1.LP mice
      that are low responders to Pn and express lower levels of T15 Id as compared to
      BALB/c. Young D1.LP mice produced high numbers of auto-anti-T15 AFC of both IgM
      and IgG isotypes following a single immunization with Pn vaccine. The kinetics of
      auto-anti-T15 response in D1.LP mice was similar to that of the antigen-specific
      response. These results demonstrate that the ability of the immune network to
      produce autologous antibody to a shared Id depends on the genetic makeup of the
      host, and that this response may be regulated by the level of Id expression.

PMID- 1394447
TI  - Tumor cytostasis mediated by LPS- or PSK-activated human plastic-adherent
      peripheral blood mononuclear cells.
AB  - We investigated the mechanism of cytostasis mediated by activated human plastic
      adherent peripheral blood mononuclear cells (PBMC) in two cell lines, L.P3 cells
      (TNF alpha sensitive) and A375 cells (TNF alpha insensitive), using two
      biological response modifiers, lipopolysaccharide (LPS) and a protein-bound
      polysaccharide extracted from a fungus, PSK. In L.P3/LPS, L.P3/PSK, and A375/LPS
      cultures, the cytostatic effects were significantly reversed by anti-TNF alpha
      antibody, while in the A375/PSK culture they were not. In concordance with this,
      LPS was a good inducer of TNF alpha, but PSK was not. In A375/PSK culture, PSK
      activated cells arrested A375 cells at the boundary between G1 and S, presumably
      through inhibition of polyamine synthesis. This growth inhibition may be mediated
      by an unknown soluble factor which is different from TNF alpha, IL-1, IL-6, and
      TGF beta.

PMID- 1394449
TI  - Suppression of chronic antigen-induced arthritis in rats by a monoclonal antibody
      against the T cell receptor alpha beta.
AB  - We have investigated a role for T cells in chronic antigen-induced arthritis in
      rats employing a monoclonal antibody (R73 mAb) against the T cell receptor alpha
      beta. Treatment with R73 mAb from the time of intra-articular antigenic challenge
      blocked completely the induction of chronic, but not acute ovalbumin-induced
      arthritis in sensitized rats. Histologically, treatment-controlled arthritic rats
      exhibited marked hyperplasia of synovial membrane with pronounced infiltration of
      inflammatory cells including alpha beta + T cells in the chronic phase of
      arthritis. In contrast, R73 mAb-treated rats had almost normal joint histology.
      Treatment with R73 mAb after onset of arthritis was also effective in suppressing
      the progression of chronic antigen-induced joint inflammation. The preventive and
      suppressive effects of the mAb on chronic antigen-induced arthritis were
      associated with marked depletion of alpha beta + T cells in peripheral blood. The
      DTH but not the humoral response to ovalbumin in sensitized rats was suppressed
      significantly by R73 mAb. Thus, alpha beta + T cells appear to have a central
      role in both induction and progression of chronic antigen-induced arthritis.

PMID- 1394448
TI  - Characterization of T cell proliferative responses induced by anti-Qa-2
      monoclonal antibodies.
AB  - The MHC class I Qa-2 Ag are attached to the cell surface by a
      glycanphosphatidylinositol (GPI) anchor. Crosslinking of Qa-2 and several other
      cell surface Ag attached by the GPI linkage has been shown to lead to cell
      activation. We have developed 10 new anti-Qa-2 mAb and characterized their
      capacity to induce proliferation of spleen cells. In the absence of anti-Ig
      mediated crosslinking, none of the mAbs alone could induce activation. However,
      mAb 23.1 which reacts with the alpha 3 domain of Qa-2, when combined with most of
      the other mAbs (alpha 1, alpha 2 domain reactive), activated cells in the absence
      of anti-Ig crosslinking. The mAb pair 23.1 plus 24.16 was the most proficient and
      induced proliferation in the absence of any exogenous second signals. Responses
      were greatly enhanced and equivalent to those seen with anti-CD3 by the addition
      of phorbol myristate acetate (PMA). Ionomycin, rIL-2, or rIL-4 also potentiated
      anti-Qa-2 responses but less efficiently than PMA. Significant strain variation
      in the magnitude Qa-2-mediated proliferative responses was observed correlating
      with the levels of Qa-2 expressed on the cell surface. Crosslinking of Qa-2
      molecules by the mAb combinations was required because monovalent Fab fragments
      failed to activate cells. F(ab')2 fragments of mAb 23.1 plus 24.16 induced
      vigorous proliferation indicating that accessory cell presentation of the mAb via
      Fc receptors was not required. Immobilized (plate bound) anti-Qa-2 mAb induced
      proliferation suggesting that the Qa-2 pathway may be distinct from that of other
      GPI molecules such as Thy-1 and Ly-6. Populations enriched for T cells
      (approximately 95%) responded as well as whole spleen cells, whereas B
      lymphocytes failed to proliferate to anti-Qa-2. Both CD4+ and CD8+ cells were
      activated following crosslinking of Qa-2. Finally, T cell activation mediated by
      Qa-2 induced elevation of [Ca2+]i, IL-2R expression, and the release of IL-2.
      These data demonstrate that crosslinking of Qa-2 on T lymphocytes represents a
      potent pathway for inducing cell activation.

PMID- 1394450
TI  - Comparison of the capacity of murine and human class I MHC molecules to stimulate
      T cell activation.
AB  - The mechanism underlying the apparent differences in the capacity of murine and
      human class I MHC molecules to function as signal transducing structures in T
      cells was examined. Cross-linking murine class I MHC molecules on splenic T cells
      did not stimulate an increase in intracellular calcium ([Ca2+]i) and failed to
      induce proliferation in the presence of IL-2 or PMA. In contrast, modest
      proliferation was induced by cross-linking class I MHC molecules on murine
      peripheral blood T cells or human class I MHC molecules on murine transgenic
      spleen cells, but only when costimulated with PMA. Moreover, cross-linking murine
      class I MHC molecules or the human HLA-B27 molecule on T cell lines generated
      from transgenic murine splenic T cells stimulated only modest proliferation in
      the presence of PMA, but not IL-2. On the other hand, cross-linking murine class
      I MHC molecules expressed by the human T cell leukemic line, Jurkat, transfected
      with genes for these molecules, generated a prompt increase in [Ca2+]i, and
      stimulated IL-2 production in the presence of PMA. The results demonstrate that
      both murine and human class I MHC molecules have the capacity to function as
      signal transducing structures, but that murine T cells are much less responsive
      to this signal.

PMID- 1394452
TI  - Transforming growth factor-beta inhibits the production of IgG, IgM, and IgA in
      human lymphocyte cultures.
AB  - Transforming growth factor beta (TGF beta) has potent immunoregulatory effects
      acting on both T and B cells. It strongly inhibits secretion of IgG and IgM in
      human and murine B cell cultures, but has been shown to have an enhancing effect
      on IgA production in the mouse. We have studied the effect of TGF beta on the
      production of IgA in human lymphocyte cultures. The addition of TGF beta to
      pokeweed-stimulated peripheral blood lymphocytes resulted in a suppression of IgA
      production of both subclasses, similar in magnitude to the suppression of IgG and
      IgM production. Membrane IgA expression was not increased by culturing tonsillar
      lymphocytes with TGF beta. In conclusion, we find no evidence for a selective
      enhancing effect of TGF beta on IgA synthesis in humans, in contrast to the
      findings reported in mice.

PMID- 1394451
TI  - Priming of peripheral lymph node B cells with TNP-Ficoll: role of lymphokines in
      B cell differentiation.
AB  - We have previously shown that peripheral lymph node (PLN) B lymphocytes of adult
      DBA/2J mice failed to make an antibody response to type 2 antigen TNP-Ficoll, but
      exhibited a good antibody response to type 1 antigen TNP-Brucella abortus. In the
      present study we wanted to find out whether the unresponsiveness of PLN B cells
      to TNP-Ficoll is due to defects in the early activation and proliferation stage
      or in the final differentiation stage of B cells. Therefore, we have used a two
      step protocol of in vivo immunization of mice with TNP-Ficoll and the subsequent
      in vitro challenge with TNP-Brucella abortus and studied the anti-TNP plaque
      forming cell (PFC) responses. The results indicate a three- to sixfold increase
      of PFC responses in PLN cell cultures derived from TNP-Ficoll-primed animals
      compared to saline control mice. This increased antibody response was TNP
      specific as 93% of the PFC's were inhibited by TNP-lysine. Limiting dilution
      experiments confirm that the increase in anti-TNP PFC response from the TNP
      Ficoll-primed animals was indeed due to an increase in TNP-specific precursor B
      cells. Further, the addition of rIL-5 or rIL-6 induced anti-TNP PFC in the TNP
      Ficoll-primed and in control PLN cell cultures in the presence of antigen.
      However, in primed PLN cells lymphokines alone were sufficient to restore anti
      TNP PFC response. In conclusion, our results show that in PLN, the TNP-Ficoll can
      induce proliferation of hapten-specific B cells but not final differentiation.
      These primed PLN B cells mature into antibody-secreting cells upon stimulation
      with TNP-BA or lymphokines.

PMID- 1394453
TI  - Induction of syngeneic cytotoxic T lymphocytes against a B cell tumor. II.
      Characterization of anti-idiotypic CTL lines and clones.
AB  - In an earlier communication we showed that idiotypic immunoglobulin (Id+ Ig) of a
      B cell hybrid, 2C3, can induce cytotoxic T lymphocytes (CTL) in the spleens of
      mice that are hyperimmunized with the irradiated tumor cells. To understand the
      extent of heterogeneity in the splenic CTL population, stable anti-idiotypic CTL
      lines and clones were established from 2C3-primed splenocytes. One representative
      CTL line A102 which exhibited the phenotype of CD3+, CD4-, and CD8+, has been
      maintained in long-term culture for more than 18 months. Cytotoxic specificity of
      A102 was determined by cold target inhibition assay using a panel of syngeneic
      and allogeneic B cell tumors. The CTL line A102 was highly cytotoxic to 2C3, only
      weakly to other syngeneic tumors, but not at all to allogeneic B cell tumor CH12.
      Furthermore, CTL-mediated cytolysis was significantly abrogated by blocking 2C3
      cells with anti-idiotypic monoclonal and polyclonal antibodies. These results
      clearly show that 2C3 Id represents the immunodominant epitope(s) recognized by
      the CTL line A102. To isolate a highly Id-specific effector population, A102 was
      repeatedly subcloned by limiting dilution. One such clone 102.F5 exhibited
      considerable specificity toward Id+ 2C3 while another clone 102.E10 showed no
      such specificity in a competitive cytotoxicity assay. This was further confirmed
      by the inhibition studies with anti-Id mAb. Thus, hyperimmunization with
      irradiated 2C3 cells evokes a spectrum of anti-2C3 cytotoxic effector cells, of
      which a major population is reactive to the idiotypic determinants associated
      with 2C3 Ig.

PMID- 1394454
TI  - Induction of syngeneic cytotoxic T lymphocytes against a B cell tumor. III. MHC
      class I-restricted CTL recognizes the processed form(s) of idiotype.
AB  - The purpose of this work was to determine the molecular nature of the idiotypic
      Ig of a B cell tumor, 2C3, involved in the induction of anti-idiotypic cytotoxic
      T-lymphocytes (CTL). We previously reported that hyperimmunization of mice with
      irradiated 2C3 cells provides effective tumor protection by inducing MHC class I
      restricted CTL. Due to the enormous heterogeneity of the splenic CTL further
      study could not be undertaken on the idiotype (Id)-CTL interaction. Subsequently
      an anti-idiotypic CTL line, A102, and a highly Id-specific CTL clone, 102.F5,
      have been developed. In the present investigation we report that the processed
      forms of idiotypic determinants are responsible for induction and activation of
      these specific effector CTL. Inhibition studies using anti-TcR and anti-MHC class
      I mAbs showed that the TcR-CD3 complex of the anti-idiotypic CTL recognized 2C3
      Id in the context of MHC class I antigens. The cytotoxicity of these CTL could
      not be inhibited with affinity-purified 2C3 Ig used as such or after pulsing with
      splenic antigen-presenting cells (APC). Furthermore, using brefeldin A (BFA) and
      chloroquine (CLQ), which are specific inhibitors of cytosolic and endosomal
      antigen processing pathways, respectively, it has also been observed that
      exposure of 2C3 to BFA but not CLQ prevents its cytolysis by both anti-idiotypic
      CTL line and clone. These results clearly indicate that endogenously produced
      idiotypic determinants of 2C3 Ig are processed in pre-Golgi vesicle, possibly in
      the ER, along with MHC class I antigens and then are transported to the membrane.
      Treatment of 2C3 with BFA, however, did not exert any effect on the expression of
      membrane-associated Ig of 2C3 cells. Therefore, it is the processed form rather
      than the bona fide receptor Ig on the cell surface that is recognized by the Id
      specific CTL.

PMID- 1394455
TI  - Rethinking the AIDS conundrum.

PMID- 1394456
TI  - Gene transfer into mammalian somatic cells in vivo.
AB  - Direct gene transfer into mammalian somatic tissues in vivo is a developing
      technology with potential application for human gene therapy. During the past 2
      years, extensive progress and numerous breakthroughs have been made in this area
      of research. Genetically engineered retroviral vectors have been used
      successfully to infect live animals, effecting foreign gene expression in liver,
      blood vessels, and mammary tissues. Recombinant adenovirus and herpes simplex
      virus vectors have been utilized effectively for in vivo gene transfer into lung
      and brain tissues, respectively. Direct injection or particle bombardment of DNA
      has been demonstrated to provide a physical means for in situ gene transfer,
      while carrier-mediated DNA delivery techniques have been extended to target
      specific organs for gene expression. These technological developments in
      conjunction with the initiation of the NIH human gene therapy trials have marked
      a milestone in developing new medical treatments for various genetic diseases and
      cancer. Various in vivo gene transfer techniques should also provide new tools
      for basic research in molecular and developmental genetics.

PMID- 1394457
TI  - Roles of immobilized glycosylated proteins and lipoprotein(a) in adhesivity of
      endothelial cells: possible implications for atherogenesis.
AB  - The adherence of peripheral blood monocytes to adult bovine endothelial cells
      grown to confluence in the microplates was studied. The microplates were coated
      with different proteins or used without special treatment. It was shown that
      endothelial cells seeded on immobilized glycosylated proteins (serum albumin or
      skin gelatin) adhered more monocytes than the cells grown on non-modified
      proteins. Endothelial cells grown in lipoprotein(a) coated wells bound more
      monocytes than the cells grown in non-treated microplates or in wells coated with
      low density lipoproteins (LDL). The effect of lipoprotein(a) coating could not be
      reproduced by treating the plates with plasminogen (as a homolog of apo(a)) or
      with a mixture of LDL and plasminogen. These results indicate that the
      composition of extracellular substrata has a profound effect on adhesive
      properties of cultured endothelial cells. The implications of these findings for
      atherogenesis and for the general aspects of regulation of cell adhesion are
      discussed.

PMID- 1394458
TI  - An acid extract from dissociation medium of sea urchin embryos, induces
      mesenchyme differentiation.
AB  - When material extracted by 1 M acetic acid from the dissociation medium of sea
      urchin embryos is added at low concentrations to isolated primary mesenchyme
      cells, it induces skeletogenesis. The same material added to dissociated blastula
      cells, or to embryos at the blastula stage, stimulates skeleton formation and
      pigment cell differentiation. On dissociated cells, it also increases cell
      reaggregation, thymidine incorporation and survival. On embryos, it induces
      exogastrulation and appearance of extraembryonic pigment cells. The activity of
      the extract is resistant to raised temperatures and partially to tryptic
      digestion but is abolished by trypsin treatment followed by heating. The active
      fraction does not readily filter through Amicon XM-50 and is retarded by column
      chromatography on Bio-Gel P-60.

PMID- 1394459
TI  - The inhibitory effect of anthranilate derivatives on HCO3-/Cl- exchange in red
      blood cells of human, pigeon and trout.
AB  - All ten of anthranilate derivatives were found to be inhibitors of HCO3-/Cl-
      exchange in human, trout and pigeon red blood cells. The individual l50 values
      covered a range of 2-3 orders of magnitude for human, trout and pigeon RBCs. The
      results obtained confirm that the anion transporting region of the band 3 protein
      in human, trout and pigeon red blood cells are highly preserved even though the
      RBCs belong to animals living in entirely different habitats. However, in spite
      of the general similarities, significant differences between human trout and
      pigeon red blood cells could be observed. They could be attributed to differences
      of the hydrophobic character of the various probes.

PMID- 1394460
TI  - Spindle poles in higher plant mitosis.

PMID- 1394461
TI  - Timing of mitotic chromosome loss caused by the ncd mutation of Drosophila
      melanogaster.
AB  - We studied the timing of mitotic loss of maternally and paternally derived
      chromosomes among the progeny of Drosophila melanogaster females homozygous for
      an amorphic mutation in ncd, a gene encoding a kinesin-like protein. In order to
      determine the division at which chromosome loss occurs, we estimated the fraction
      of XO nuclei resulting from X chromosome loss by scoring the phenotype of 47
      adult cuticular landmarks in 160 XX-XO mosaics (gynandromorphs) derived from
      maternal X chromosome loss, and 33 gynandromorphs derived from paternal X
      chromosome loss. The results show that while most of the mitotic loss of
      maternally derived chromosomes occurs at the first cleavage division, the mitotic
      loss of paternally derived chromosomes occurs only at the second and later
      divisions. This means that paternally derived chromosomes are immune from the
      effects of ncd prior to karyogamy, which occurs after the first cleavage
      division. We discuss the implications of these results for the function of the
      ncd gene product and for other kinesin-like proteins in Drosophila.

PMID- 1394462
TI  - Distribution of detyrosinated microtubules in motile NRK fibroblasts is rapidly
      altered upon cell-cell contact: implications for contact inhibition of
      locomotion.
AB  - Fibroblasts migrating into an experimental wound contain an extensive array of
      detyrosinated microtubules (Glu MTs) oriented in the direction of migration,
      whereas nonmotile cells in the interior of a monolayer contain Glu MTs that are
      primarily coiled around the nucleus. To determine the role of cell-cell contact
      in the formation of these distinct arrays of Glu MTs, we studied the distribution
      of Glu MTs by immunofluorescence in NRK fibroblasts that had been fixed at
      different intervals after they had established contact with other cells. Time
      lapse video recordings were made of the contacting cells to provide a record of
      cellular behavior. In motile cells that became completely surrounded by virtue of
      contact with other cells, Glu MTs were found mostly coiled around the nucleus.
      The proportion of cells whose Glu MTs extended to the original leading edge
      decreased dramatically after the cells had been surrounded for 10 min or more. At
      earlier times, when the contact was confined to a portion of the cell margin, Glu
      MTs were absent from the area behind the contact site, yet were still oriented
      toward the noncontacting and ruffling margins. The contact-induced alteration of
      Glu MTs was not due to the cessation of forward locomotion of cells per se, since
      immobilization of cells with cytochalasin D did not cause a dramatic change in
      Glu MTs. That cell-cell contact also specifies the type of Glu MTs formed in
      cells was shown by experiments in which MTs were regrown following complete
      depolymerization with nocodazole. The remodeling of Glu MTs during cell-cell
      contact may be involved in cellular repolarization during contact inhibition of
      locomotion and will be a useful marker for further dissecting the molecular
      events of contact inhibition of motility.

PMID- 1394463
TI  - Evolution of the flagellar waveform of ram spermatozoa in relation to the degree
      of epididymal maturation.
AB  - Motility and flagellar movement of ram spermatozoa along the epididymis were
      analysed in vitro. From the caput to the cauda of the epididymis, the percentage
      of motile and progressive spermatozoa increases. No flagellar bending was
      observed in spermatozoa from the testis or the epididymal anterior caput. When
      spermatozoa reached the distal caput of the epididymis, a static curvature,
      associated with an initiation of the flagellar beating, appeared on the flagella.
      This curvature normally disappeared during epididymal transit. Its disappearance
      was associated with an increase in the flagellar beat efficiency. Our results
      suggest that the initiation of motility is related to two mechanisms involving:
      (1) the presence of a transient static curvature, and (2) the establishment of a
      symmetric regular beating of the flagellum.

PMID- 1394464
TI  - Image blurring by thermal diffusion in the observation of hydrated biomolecules
      with soft X-ray microscopy.
AB  - A simple model is presented for the estimation of image blurring in X-ray
      microscopy of biological specimens in a hydrated environment. The model is
      essentially based on thermal diffusion of an object to be imaged. The degree of
      image blurring by diffusion depends on the following situations of the object.
      The object is free from, is tightly fixed to, or is partially connected to the
      surrounding structures. The proper imaging time required to achieve a given
      resolution in X-ray microscopy of biological structures was estimated with the
      present method. The results suggest that imaging time shorter than 3 msec (free)
      to 1.4 sec (tightly fixed) is required for the observation of a cell (30 microns
      in diameter) at the resolution of 100 nm. The model is also applicable to a
      fragmented object caused by imaging X-rays.

PMID- 1394465
TI  - Novel monoclonal antibody mAb G3A5 recognizes 138-kDa glycoprotein localized on
      the Golgi membrane.
AB  - Partially purified Golgi membranes of HeLa cells were used as antigen to produce
      a novel monoclonal antibody (mAb G3A5). The mAb G3A5 specifically labeled Golgi
      apparatus of human and monkey cultured cells as ascertained by indirect
      immunofluorescence but did not stain those of bovine or mouse cells. Treatment
      with nocodazole and brefeldin A (BFA) induced fragmentation and redistribution of
      the staining. Western immunoblot analysis showed that mAb G3A5 was directed
      against a single polypeptide with an apparent molecular mass of 138-kDa (p138
      antigen). The p138 antigen is an integral membrane protein of the Golgi
      apparatus, as assessed by several assays: protease protection, salt wash and
      flotation in sucrose density gradient centrifugation. The p138 antigen was
      purified using immunoaffinity chromatography. The apparent molecular mass of the
      p138 antigen decreased by 2 to 4 kDa after treatment with the peptide: N
      glycosidase F, while digestion with ENDO F or Neuraminidase did not have this
      effect. Thus, p138 antigen is a glycoprotein containing asparagine-linked
      carbohydrates.

PMID- 1394466
TI  - A cell line derived from sphingomyelinosis mouse shows alterations in
      intracellular cholesterol metabolism similar to those in type C Niemann-Pick
      disease.
AB  - Cell lines derived from the sphingomyelinosis (gene symbol, spm) mouse were
      established from homozygous (spm/spm) and heterozygous (spm/+) embryos according
      to a rigid 3T3 transfer schedule. The SPM-3T3 cells derived from a homozygous
      embryo showed extensive accumulation of intracellular cholesterol, attenuated
      esterification of exogenously added cholesterol and increased de novo cholesterol
      synthesis, when compared to SPMH-3T3 cells derived from a heterozygous embryo.
      The phenotypic abnormalities were very similar to those observed in fibroblasts
      from patients with Niemann-Pick disease type C (NP-C), in which a defect in the
      intracellular transport of unesterified cholesterol is suggested. The genetic
      defect in SPM-3T3 cells should be closely related to that in NP-C. The SPM-3T3
      cell line is useful for biochemical and genetic studies on the regulation of
      intracellular cholesterol metabolism.

PMID- 1394467
TI  - [Use of the immunoblotting method in serodiagnosis of M. kansasii
      mycobacteriosis].
AB  - The indirect enzyme test ELISA with soluble complex antigen of M. kansasii, used
      for assessment of the titre of IgG serum antibodies in a group of patients
      suffering from mycobacteriosis M. kansasii and in a control group of patients
      suffering from tuberculosis did not reveal statistically significant differences
      between serological responses of these two groups. On the other hand, the
      immunoblot analysis revealed in sera selected at random from these two groups
      differences at the level of subprotein units against the complex antigen of M.
      kansasii. In a group of 15 sera of patients with M. kansasii the immunodominant
      area was 42-45 kD protein subunits, in the control group of 10 sera with M.
      tuberculosis the area was 35-39 kD. The western blot technique is more
      perspective for improvement of the serum diagnosis of M. kansasii, in particular
      where a specific antigen is not available.

PMID- 1394468
TI  - [A methods of processing and microbiological study of sputum].
AB  - In the submitted paper the author discusses quantitative and qualitative methods
      of examination of sputum, using different reagents for blending and lysis of
      sputum. The micromodification of Dixon-Miller's method is most effective from the
      economic aspect and as regards quality of the examination. The dilution method
      makes it possible, using selective media, to complete the whole examination in a
      shorter time without using special equipment for cultivation and assessment of
      sensitivity to antibiotics in ordinary microbiological field laboratories.

PMID- 1394469
TI  - [Detection of mycobacteria in pathologic material using the radiometric method].
AB  - For concurrent detection of mycobacteria by the radiometric method BACTEC and the
      standard cultivation technique 96 samples of pathological material from patients
      hospitalized with suspected or confirmed tuberculosis was used. The total number
      of positive samples was 30, using the BACTEC method only, four samples and using
      the cultivation method only, 10 samples. The assessed difference was not
      statistically significant. The mean period of positivity with the BACTEC method
      was 20.4 days, in cultivations 28.8 days. The higher yield of the cultivation
      method could be caused by various factors. For the BACTEC system inocula of 0.5
      ml were used and one cultivation bottle, for the cultivation inocula 1.0 ml and
      four test tubes for one sample were used. From five samples, positive only on
      cultivation, only sporadic colonies were obtained after 42-63 days cultivation
      and in all instances only on one of four media.

PMID- 1394470
TI  - [The present epidemiologic status and prognosis in measles].
AB  - During 1990 and partly also 1991, after a practically 10-year zero incidence of
      measles on the territory of the Czech Republic a measles epidemic broke out. The
      most severely affected group were adolescents aged 15-19 years who were immunized
      only by a single dose of vaccine. Conversely the lowest morbidity was recorded in
      2-9-year-old children who were immunized already with two doses. The cause of the
      epidemic was primary failure of the vaccine leading to a low level of collective
      immunity in some population age brackets. The authors discuss and explain the
      strategy of immunization against measles involving two doses of vaccine after a 6
      10-month interval. In the conclusion possibilities to achieve permanent
      elimination of measles on our territory are discussed.

PMID- 1394471
TI  - [Isolation of a rare serovar of Plesiomonas shigelloides].
AB  - The authors describe the isolation of a rare serovar Plesiomonas shigelloides
      from a patient with diarrhoea. The isolated strain belongs according to a
      combined Japanese-Czechoslovak antigenic scheme to serovar 024 H"o". The
      interesting finding draws attention to the possibility of routine departments to
      contribute to investigations of the incidence, importance and antigenic structure
      of this bacterial species.

PMID- 1394472
TI  - [Knowledge of high school students about HIV and AIDS].
AB  - In 475 students attending the last school year in four high schools in the town
      of Povazska Bystrica, Slovakia a questionnaire survey of students' knowledge of
      HIV infection and AIDS was carried out. 76.33% of all answers to questions in the
      questionnaire were correct. We found no significant differences between the
      percentage of correct answers among schools, among boys and girls and among
      students living in the country and in town. 56% of the students fought that there
      is enough information about HIV infection, AIDS and about prevention of that
      infection. Nevertheless the percentage of correct answers to some questions in
      the questionnaire do not correspond to this statement.

PMID- 1394473
TI  - [Bacterial contamination of arthropods in a health facility].
AB  - At 55 sites of a health institution in July and September 1990 a total of 161
      specimens of arthropods were detected, 30 outdoors and 131 on the premises of the
      health institution. On their bodies 116 bacterial strains were isolated, mostly
      Gram-negative rods (more than 85%), in particular spp. Enterobacter,
      Acinetobacter, Klebsiella, Citrobacter and Pseudomonas. Gram-positive cocci
      accounted for cca 12%, in particular strains of S. haemolyticus and S. hominis.
      The greatest number of strains was detected on bodies of cockroaches, flies,
      Chironomus and Tenebrio. In about one third of strains the diffuse disk test
      revealed resistance to more than three antibiotics. The investigation was
      supplemented by microbiological examination of strains from a hospital
      environment (45 smears) and strains from biological material (82 specimens), from
      patients with nosocomial infections.

PMID- 1394474
TI  - [Helminthologic examination of swimming pool water in Czechoslovakia].
AB  - The author evaluated conditions necessary for the development of the most common
      intestinal helminths in swimming pools and emphasizes provisions which prevent
      their development. The author recommends helminthological examinations only in
      indicated cases.

PMID- 1394475
TI  - [Examination of ticks for the presence of Borrelia sp. in Kosice and the
      surrounding region. Preliminary results].
AB  - The authors present preliminary data on the infestation of ticks Ixodes ricinus
      with Borrelia in the town of Kosice and surroundings. The authors found a mean
      4.7% positivity which means that more systematic attention should be paid to the
      problem.

PMID- 1394476
TI  - [Detection of Chlamydia trachomatis in clinical material 1989-1990].
AB  - Examination of 276 smears and scrapings from the uterine cervix of women before
      delivery and during the puerperium revealed in 28.0% positive findings. Perinatal
      infection was confirmed by the presence of Chlamydia trachomatis in 35.5%
      neonates with conjunctivitis and 27.3% positive smears from the nasopharynx. The
      authors used the direct immunofluorescence method. For immunofluorescent staining
      they used Chlamyset of Orion Co., Finland.

PMID- 1394477
TI  - [Comment on the microbiological procedures in the Rate Schedule of the General
      Health Insurance Company].

PMID- 1394478
TI  - [Use of DNA probes for identification of mycobacterial species].

PMID- 1394479
TI  - [Antimicrobial activity of selected aqua-carboxyl-cupric complexes].
AB  - The activity of compounds of different structural types of aqua-complexes of the
      composition Cu(R-COO)2.nH2O-methoxybenzoatocupric complexes, R = 2-, 3- and 4
      methoxyphenyl (n = 1, 1 and 3); aryloxyacetatocupric complexes, R = phenoxymethyl
      (n = 3), 2-, 3- and 4-chlorophenoxymethyl (n = 4, 2 and 2) and 1-naphthoxymethyl
      (n = 4), and furthermore isomeric furanecarboxylato-(R = 2- or 3-furyl, n = 3, or
      1) and thiophencarboxylatocupric complexes (R = 2- or 3-thienyl, n = 1 and 1),
      was examined by the methods of the 1st screening on selected anthropo- and
      phytopathogenic microorganisms. The effects of all aqua-complexes (suspension
      dosage form) on the representatives of bacteria and yeasts are minimal. On the
      other hand, the effect of these substances on the causative agents of
      dermatomycoses (Trichophyton terrestre, Microsporum gypseum) in the case of
      methoxybenzoato- and furoatocupric complexes achieves a MIC value of 500
      micrograms/cm3 and lower. The activity against phytopathogenic fungi (both in
      vitro and in vivo experiments) is generally relatively low at 0.05% concentration
      of active ingredients (dispersible powders). At the same time the antimicrobial
      activity of the pertinent free carboxylic acids was investigated in relation to
      the cupric salts being formed. They are able to form the required pharmacoactive
      form prevalently as late as they are in the form of aqua-carboxylatocupric
      complexes.

PMID- 1394480
TI  - [Biological effects of anthraglycosides. I. Laxatives].

PMID- 1394481
TI  - [Does the spermatozoa survival test correlate with fertilization of oocytes in
      vitro?].
AB  - The spermatozoa survival test (SST)--which is used in our laboratory is
      considered to be a relatively simple test with a large probability determining
      the ability of spermatozoa to fertilize oocytes in vitro. The SST reveals the
      percentage of motile spermatozoa after 20hr. cultivation with an oocyte. 221
      sperm samples used for oocyte fertilization were analyzed and divided into four
      groups: normospermia (123 samples), oligospermia (19), asthenospermia (45) and
      oligoasthenospermia (34). The results show a significant reduction of the
      fertilization rate (< 35%) below the range of 40% SST in all groups. Above the
      value of 40% motile spermatozoa after 20hr. cultivation is the fertilization rate
      in all groups higher (> or = 50%). The authors recommend the SST as a part of the
      screening examination before the couple is admitted to an assisted reproduction
      programme.

PMID- 1394482
TI  - [Results of surgical treatment of ovarian dysfunction].
AB  - The authors operated 155 women where ovarian dysfunction was the cause of
      infertility. The first group was formed by 125 women with the Stein-Leventhal
      syndrome, the second group was formed by 30 women with dysgenesis of the gonads,
      karyotype, 46,XX. In the first group 97 of the operated women (77.6%) became
      pregnant. In the latter group after mere resection of the gonads 45 women (36%)
      became pregnant. After combined therapy (surgery and hormonal therapy) 52
      infertile women (41.6%) became pregnant. Twenty-eight patients (22.4%) did not
      become pregnant. In the second group, i.e. in the group of gonadal dysgenesis 7
      of 16 women (44%) became pregnant but only in the group of sclerocystic
      dysgenetic gonads. None of the women with streak or hypoplastic gonads became
      pregnant. In gonadal dysgenesis it is important to assess the quality of the
      follicular apparatus. For successful surgery of the ovary it is necessary to
      preserve a maximum of functional tissue and to use a careful surgical technique.

PMID- 1394483
TI  - [Treatment of vesicovaginal fistulas].
AB  - The authors evaluated in a retrospective analysis their experience with treatment
      of vesicovaginal fistulae in 36 patients. Most frequently--almost in 90%--the
      fistulae developed after a gynaecological operation, in particular surgery on
      account of benign, but also malignant disease. The authors used for surgical
      correction of the fistulae a transvaginal approach in 28 (77.8%) patients, a
      transvesical approach in 5 (13.9%) patients and a transvesical and
      transperitoneal approach in two (5.5%) patients. One fistula receded
      spontaneously during drainage of the urinary bladder. Primary correction of the
      fistula was successful in 34 (94.4%) patients. In two patients further surgical
      treatment was necessary. With regard to their favourable experience the authors
      recommend a transvaginal approach which is in their opinion suited for the
      majority of non- complicated vesicovaginal fistulae. In corrections of extensive
      fistulae after radiotherapy a combined transvesical and transperitoneal approach
      with fixation of the omentum in the space between the vagina and urinary bladder
      proved useful.

PMID- 1394484
TI  - [Diagnosis of malignant ovarian tumors using color Doppler sonography].
AB  - In a prospective investigation the authors followed the circulation in 32
      patients with ovarian tumours before operation. They examined the RI using colour
      Doppler sonography. Based on histological examination the authors divided the
      patients into groups with malignant and benign tumours resp. The peripheral
      resistance and RI in the group of patients with malignant tumours was 0.35 +/-
      0.03, i.e. significantly lower than in the group with benign tumours, 0.65 +/-
      0.08 (p < 0.001). In none of the patients with malignant tumours the RI was
      higher than 0.50. The authors recommend this method as a screening examination
      for early detection of malignant ovarian tumours.

PMID- 1394485
TI  - [Detection of intrauterine fetal growth retardation using ultrasound fetometry].
AB  - Based on ultrasonic foetometry at an interval of 0-59 days before delivery the
      authors assessed in 93 women with risk pregnancies hospitalized during the 31st
      43rd week of gestation the index of the femur length/abdominal circumference
      independent on gestation age, and they estimated the foetal weight by means of
      three logarithmic formulae comprising the biparietal diameter, femur/length and
      abdominal circumference. For detection of foetal hypotrophy, the estimated weight
      of the foetus in particular according to the formula of Hadlock et al.
      (sensitivity 58.3%, specificity 94.22%) was significantly more accurate than the
      index of femur length/abdominal circumference > or = 23.0 (sensitivity 45.8%,
      specificity 91.3%).

PMID- 1394486
TI  - [Amniocentesis in the diagnosis of threatened premature labor].

PMID- 1394487
TI  - [Diagnosis of fetal hypoxia based on the acid-base equilibrium in the umbilical
      artery].

PMID- 1394488
TI  - [Personality changes in women after induced abortion].

PMID- 1394489
TI  - [Adenocarcinoma of the uterus in a young girl--therapeutic considerations].

PMID- 1394490
TI  - [Successful completion of pregnancy in an infertile couple after immunization of
      the pregnant woman with a skin graft].

PMID- 1394491
TI  - [The thyroid gland and fertility].

PMID- 1394492
TI  - [Drug therapy of urgency urinary incontinence in women].

PMID- 1394493
TI  - [History of women's health services in Czechoslovakia. II].

PMID- 1394494
TI  - [Prophylactic administration of Claforan in patients with premature loss of
      amniotic fluid].
AB  - The authors compared two groups of pregnant women with early loss of amniotic
      fluid. In the first group Claforan was administered, 3 x 1 g by the i.m. route,
      and in the second group Ampicillin, 3 x 1 g by the i.m. route. The data were
      recorded in a special protocol and were divided into three groups: 1. patient
      before delivery, 2. patient during puerperium, 3. neonate. From the results two
      conclusions were drawn: 1. The authors did not detect any reasons why antibiotics
      should not be administered prophylactically in case of premature loss of amniotic
      fluid. 2. The main differences between the compared groups were found in neonates
      where after administration of Claforan there was a substantially lower incidence
      of positive bacterial cultures than after Ampicillin and there was also a lower
      incidence of RDS II and adnatal infections.

PMID- 1394495
TI  - [Does transabdominal amniocentesis in the 2d trimester affect fetoplacental
      circulation?].
AB  - In a prospective study the authors focused attention on Doppler sonographic
      examination of the foetoplacental circulation and whether it is influenced by
      transabdominal amniocentesis. They examined 124 pregnant women subjected during
      the 17th or 18th week of pregnancy to amniocentesis in the out-patient
      department. Before amniocentesis and soon after it they examined the flow in the
      uterine artery on the right and in the umbilical artery. From five consecutive
      cycles they evaluated the S/D ratio and RI in both vessels and compared the
      results. They did not record any complications during amniocentesis. Evaluation
      of the results of both investigated parameters before and after amniocentesis did
      not reveal any statistically significant differences in the investigated vessels.
      Based on the assembled results, the authors assume that transabdominal
      amniocentesis, despite its invasive character, does not influence the
      foetoplacental circulation and does not have a negative impact on the course of
      pregnancy.

PMID- 1394496
TI  - [Determination of growth scales and ponderal indices in neonates].
AB  - By retrospective processing of data from 10,002 neonates the authors prepared
      tables of birth weights and heights incl. percentiles for the 28th-43rd week of
      gestation. By processing data concerning 9,893 neonates the authors elaborated
      ponderal indexes for the 32nd-43rd week of gestation. The tables make it possible
      to evaluate the nutritional status and proportionality of neonates.

PMID- 1394498
TI  - [Determination of the fertile period during the menstrual cycle in women by
      monitoring changes in crystallization of saliva with the PC2000 IMPCON
      minimicroscope].
AB  - The authors tested the possibility of assessment of fertile and infertile days
      during the menstrual cycle by investigating the crystallization of saliva by
      means of a minimicroscope PC 2000 IMPCON. They followed up for five months a
      total of 58 women where they assessed by a combination of at least three
      classical examination methods ovulatory and anovulatory cycles. They monitored a
      total of 120 cycles and examined 1649 specimens of saliva. Some women had to be
      eliminated on account of virosis during a flu epidemic (a total of 11 cycles).
      During the periovulatory period the authors recorded in ovulatory cycles the
      foreseen crystalline structures in saliva in 78.57%. In anovulatory cycles
      agreement between the expected character of the saliva specimen and anovulation
      was found in 84% of the examined cycles. In addition to structures suggesting
      fertile or infertile days, the authors identified also intermediary types. In the
      discussion the authors analyze various aspects as regards evaluation of the
      correlation between salivary and serum levels of gonadotropins and ovarian
      steroids. They evaluate physical and chemical changes of saliva and vaginal
      secretion and discuss the problem of crystallization of the saliva during the
      menstrual cycle. Based on their findings, when testing the minimicroscope PC
      2000, they supplement the list of factors with influence the results of
      examinations. They consider PC 2000 a suitable modern equipment which extends the
      range of contraceptives and at the same time helps to assess the optimal time for
      conception in planned pregnancies.

PMID- 1394497
TI  - [Transdermal administration of estrogens in women with the postcastration and
      climacteric syndromes].
AB  - The authors report on the results of a follow-up of 64 women aged 25-64 years, to
      whom oestrogens were administered transdermally by means of the preparation
      Estraderm TTS 25 or 50 for three months. 55 women were treated for postcastration
      syndrome and nine women for climacteric syndrome. The authors deal with the
      problems of dosage of the transdermal oestrogen therapy, study the side-effects
      of treatment and evaluate the results of therapy. In conclusion, they recommend
      the transdermal form of treatment by Estraderm TTS because of its very good
      therapeutic effect, acceptability by the patients, and only minimal local and
      general side-effects.

PMID- 1394499
TI  - [Sexuality in women after treatment of malignant breast tumors].
AB  - By means of a structured interview and four questionnaires (Heterosexual
      development of woman, Sexual activity of woman, Sexual function of woman and
      Questionnaire N5 which evaluates the presence and intensity of neurotic symptoms)
      the authors examined 154 women following treatment of a malignant breast tumour.
      During the examination which took place during spa treatment the age of the
      probands was 26-67 years. The most frequent adverse subjective sensations were
      problems of nakedness when seen by healthy women, when "seening themselves" and
      when seen by the husband (partner). Adverse feelings developed most frequently
      during the first week after operation. The adaptation was worst in women aged 40
      44 years. Changes in emotional relations between partners were more favourable
      than in sexual life. Emotional as well as sex life improved in every fourth and
      more than in every 13th woman, as compared with the status before the disease.
      Men were quite tolerant. Fears and the degree of neuroticism corresponded with
      the deterioration of sexual function. Two-fifths of the women were interested in
      a reconstruction operation of the breast, however, only one in 40 of the group
      the operation was implemented or planned.

PMID- 1394500
TI  - [Increasing the rate of representative samples of oncologic cytological smears in
      gynecology].

PMID- 1394501
TI  - [Homosexuality as a biological phenomenon].

PMID- 1394502
TI  - [The history of women's health care in Czechoslovakia. III].

PMID- 1394503
TI  - [6 years' of the in vitro fertilization and embryo transfer program at the
      Institute for Maternal and Child Care in Prague-Podoli].

PMID- 1394504
TI  - [Case report of an undetected twin].

PMID- 1394505
TI  - [Rates for surgical procedures in specialties--honoraria for the so-called "small
      accounts"].

PMID- 1394506
TI  - Construction and growth properties of a yeast strain defective in sterol 14
      reductase.
AB  - We have transformed Saccharomyces cerevisiae with a genomic library contained in
      the replicative vector pFL44. The resulting transformants were screened for
      resistance to fenpropidin, a specific inhibitor of sterol 14-reductase. A plasmid
      was isolated that transformed yeast both to resistance to fenpropidin and to an
      increased specific activity of sterol 14-reductase. Sterol analysis of
      transformed cells grown in the presence of increasing concentrations of the
      inhibitor confirmed that resistance was a consequence of over-production of
      sterol 14-reductase. By chromosomal gene disruption, we have, for the first time,
      constructed yeast strains defective in sterol 14-reductase. As expected, since
      yeast in unable to take up sterols in aerobiosis, the disrupted strains do not
      grow in the presence of oxygen, even if exogenous sterols are supplied. However,
      disrupted cells grow in anaerobiosis with exogenous oleic acid and ergosterol
      supplements. They also grow in aerobiosis if they bear an additional mutation
      allowing sterol uptake. In this last growth condition the cells require a
      "sparking" ergosterol supplementation (25 nM) and accumulate ignosterol (ergosta
      8,14-dienol) as the end-product of the sterol pathway. These results reveal that
      ignosterol is not obviously toxic to yeast membranes and strongly suggest that
      the molecular basis of the antifungal-activity morpholine and piperidine is
      directly related to the specific inhibition of ergosterol formation.

PMID- 1394507
TI  - Biosynthesis of sulphur amino acids in Saccharomyces cerevisiae: regulatory roles
      of methionine and S-adenosylmethionine reassessed.
AB  - cys4-1, a mutation in the reverse trans-sulphuration pathway, relieves the
      sulphate assimilation pathway and homocysteine synthase from methionine-mediated
      repression. Since the mutation blocks the synthesis of cysteine from methionine
      downstream from homocysteine, this indicates that neither methionine nor S
      adenosylmethionine serve as low-molecular-mass effectors in this regulatory
      system, contradicting earlier hypotheses.

PMID- 1394508
TI  - The REV2 gene of Saccharomyces cerevisiae: cloning and DNA sequence.
AB  - The REV2 gene of Saccharomyces cerevisiae was cloned and sequenced; it contains
      an open reading frame of 1986 bp with a coding potential of 662 amino acids.
      Interruption of the chromosomal REV2 gene by integrating the URA3 gene coupled
      with partial deletion of the 3' terminal region produced viable haploid rev2
      delta mutants. This indicates that the REV2 gene is non-essential for growth. The
      rev2 delta mutant is slightly more UV-sensitive than strains carrying various
      rev2 alleles (rev2-1, rev2x, rad5-1, rad5-8). The putative Rev2 protein is
      probably a globular protein containing a highly conserved nucleotide-binding site
      and two zinc-finger domains.

PMID- 1394509
TI  - Genetic mapping of 1,3-beta-glucanase-encoding genes in Saccharomyces cerevisiae.
AB  - The map position of three 1,3-beta-glucanase-encoding genes in S. cerevisiae has
      been determined following conventional meiotic and mitotic mapping combined with
      recombinant DNA techniques. EXG1, EXG2 and SSG1 were localized to chromosomes
      XII, IV and XV, respectively, by hybridizing the cloned genes to Southern blots
      of chromosomes separated by pulsed-field gel electrophoresis, in conjunction with
      the rad52-1-dependent chromosome-loss mapping technique. Meiotic tetrad analyses
      further localized the EXG1 gene 6.1 centimorgans centromere-proximal to CDC25 on
      the right arm of chromosome XII. EXG2 was positioned between LYS4 and GCN2 on the
      right arm of chromosome IV, at distances of 6.2 centimorgans from LYS4 and 4.9
      centimorgans from GCN2. Finally, the SSG1 locus mapped on the right arm of
      chromosome XV, about 8.2 centimorgans to the centromere-proximal side of HIS3.

PMID- 1394510
TI  - Regulation of pho1-encoded acid phosphatase of Schizosaccharomyces pombe by
      adenine and phosphate.
AB  - Expression of pho1-encoded acid phosphatase of Schizosaccharomyces pombe has been
      reported to be regulated by phosphate. In this communication we show that it is
      also regulated by adenine. Starving adenine auxotrophic strains for adenine leads
      to a drastic increase of the enzymatic activity while adenine represses this
      activity. Full repression by adenine only occurs when phosphate is not growth
      limiting and vice versa. Regulation occurs at the level of mRNA. We isolated
      adenine non-repressible mutants. They define four genes (anr1, anr2, anr3, and
      anr5) which are involved in adenine-dependent pho1 expression. All anr mutants
      are also phosphate non-repressible. These results indicate that the generation
      and/or transduction of the intracellular signal responsible for pho1 repression
      is simultaneously dependent on both adenine and phosphate.

PMID- 1394511
TI  - An NADP(+)-dependent glycerol dehydrogenase in Aspergillus nidulans is inducible
      by D-galacturonate.
AB  - In Aspergillus nidulans there is an NADP(+)-dependent glycerol dehydrogenase that
      is specifically induced on transfer to D-galacturonate medium. In contrast to the
      previously characterised constitutive NADP(+)-dependent glycerol dehydrogenase it
      has a much broader substrate specificity, having activity as an ethanol
      dehydrogenase, and is subject to carbon-catabolite repression. In addition to the
      two NADP(+)-dependent glycerol dehydrogenases, alcohol dehydrogenase I and II are
      also present on transfer to D-galacturonate medium, and have weak activity as
      glycerol dehydrogenases.

PMID- 1394512
TI  - Structure and evolution of myxomycete nuclear group I introns: a model for
      horizontal transfer by intron homing.
AB  - We have examined five nuclear group I introns, located at three different
      positions in the large subunit ribosomal RNA (LSU rRNA) gene of the two
      myxomycete species, Didymium iridis and Physarum polycephalum. Structural models
      of intron RNAs, including secondary and tertiary interactions, are proposed. This
      analysis revealed that the Physarum intron 2 contains an unusual core region that
      lacks the P8 segment, as well as several of the base-triples known to be
      conserved among group I introns. Structural and evolutionary comparisons suggest
      that the corresponding introns 1 and 2 were present in a common ancestor of
      Didymium and Physarum, and that the five introns in LSU rRNA genes of these
      myxomycetes were acquired in three different events. Evolutionary relationships,
      inferred from the sequence analysis of several different nuclear group I introns
      and the ribosomal RNA genes of the intron-harbouring organisms, strongly support
      horizontal transfer of introns in the course of evolution. We propose a model
      that may explain how myxomycetes in natural environments obtained their nuclear
      group I introns.

PMID- 1394514
TI  - Zinc fingerprinting for Phytophthora species: ZIF markers.
AB  - We have assessed the potential of using zinc finger markers for identification of
      fungal species using Phytophthora as a model organism, since it is particularly
      difficult to classify. The results show that such markers are suitable for
      species identification of Phytophthora but do not appear to aid strain
      identification within species.

PMID- 1394515
TI  - Circular extrachromosomal DNA codes for a surface protein in the (+) mating type
      of the zygomycete Absidia glauca.
AB  - A small protein with a molecular mass of 15 kDa, which is specifically found on
      the hyphal surface of a (+) mating-type strain of the model zygomycete Absidia
      glauca, was purified to electrophoretic homogeneity and partially sequenced. The
      corresponding gene was cloned by means of an oligonucleotide probe deduced from
      the protein sequence. It could be localized on an extrachromosomal circular DNA
      element with a total length of 1250 bp. Electron microscopic analysis of A.
      glauca DNA showed that small extrachromosomal DNAs with varying length are a
      common feature of this zygomycete. There are no indications of additional
      chromosomal copies of the gene for this surface protein, and the plasmid is
      absent from DNA preparations of the (-) mating type. The copy number ranges
      around three per haploid genome, and a single transcript with a length of 400 bp,
      coding for the surface protein, could be found by employing a hybridization probe
      which spans the complete fungal plasmid. This is the first report of naturally
      occurring extrachromosomal DNA in a Mucor-like fungus, and the only example where
      an integral protein of the cell wall is encoded by a plasmid.

PMID- 1394513
TI  - Extrachromosomal ribosomal DNA of Didymium iridis: sequence analysis of the large
      subunit ribosomal RNA gene and sub-telomeric region.
AB  - The ribosomal DNA of the myxomycete Didymium iridis is organized as
      extrachromosomal linear molecules of about 20 kb, containing only one
      transcription unit of the ribosomal RNA genes. We have determined the sequence of
      the large subunit ribosomal RNA (LSU rRNA) gene as well as the sub-telomeric and
      telomeric regions. The LSU rRNA gene was found to encode a 3857 nucleotide-long
      LSU rRNA, interrupted by a transcribed spacer and two group I introns. A complete
      secondary structure model of D. iridis LSU rRNA has been constructed. The compact
      sub-telomeric region of D. iridis rDNA was found to contain several directly
      repeated sequence elements that include the simple telomere motif TTAGGG. Based
      on pairwise comparisons of LSU rRNA sequences, the time of divergence between the
      two myxomycete genera Didymium and Physarum was estimated.

PMID- 1394517
TI  - A ten-minute protocol for transforming Saccharomyces cerevisiae by
      electroporation.
AB  - We present a simplified and rapid method for the transformation of yeast cells by
      electroporation. Stationary cells, scraped off the agar of Petri dish cultures
      stored in the refrigerator for up to 6 weeks, are suspended in sorbitol buffer,
      spun down by gentle centrifugation, transferred into the electroporation cuvette,
      and immediately subjected to transformation via electroporation. Transformation
      efficiency of this 10-min method, which does not require the preparation of cell
      cultures, is about 10% of the hitherto best performing transformation procedure
      using cells of defined growth phase.

PMID- 1394516
TI  - The plastome-encoded zfpA gene of a moss contains procaryotic as well as
      eucaryotic promoter consensus sequences and its RNA abundance is modulated by
      cytokinin.
AB  - Plastid DNA of the moss Physcomitrella patens has been sequenced. An open reading
      frame (ORF 315) was identified downstream from rbcL, between trnR-CCG and psaI.
      This ORF shares homology with zfpA, a putative regulatory gene in Pisum sativum.
      The moss ORF is preceded by a Shine-Dalgarno sequence, two plastid promoter
      consensus sequences, and three TATA boxes. A specific probe detected three
      transcripts of low abundance in the wild-type moss and a cytokinin-sensitive
      chloroplast mutant. Steady state levels of zfpA transcripts were different in the
      two genotypes. In mutant protonemata treated with cytokinin, steady state levels
      of the largest transcript decreased significantly.

PMID- 1394518
TI  - High-level resistance to cycloheximide resulting from an interaction of the
      mutated pdr3 and cyh genes in yeast.
AB  - In addition to pdr3-1, the S. cerevisiae nuclear pleiotropic drug resistance
      mutant 2D was found to contain another recessive nuclear mutation, cyh,
      conferring specific resistance to cycloheximide only. The cycloheximide
      resistance level due to either the pdr3-1 or the cyh mutation alone was low and
      was not altered by the ogd1 mutation which increased the physiological
      acidification of the culture. When pdr3-1 and cyh mutations occurred
      simultaneously in the haploid yeast strain their interaction was synergistic and
      resulted in high-level resistance to cycloheximide.

PMID- 1394519
TI  - In vivo conformation of mitochondrial DNA in fungi and zoosporic moulds.
AB  - Migratory behaviour of mitochondrial DNA (mtDNA) from fungal species belonging to
      Plectomycetes, Loculoascomycetes and the zoosporic moulds, Oomycetes, has been
      studied by Pulsed Field Gel Electrophoresis (PFGE). Electrophoretic profiles
      demonstrate that long, linear molecules of a heterogenous size are the prevailing
      in-vivo form of organelle DNA in all examined species. These profiles are
      consistent with the presence of the rolling-circle mode of mtDNA replication that
      occurs in all branches of true fungi and zoosporic moulds.

PMID- 1394520
TI  - [The first stage of clinical trials of hydrogel lenses manufactured in
      Czechoslovakia].
AB  - The authors give an account of the results of the first stage of clinical trials
      of Czechoslovak disc-shaped hydrogel lenses made from the copolymer HEMA and
      methacrylic acid. Hitherto assembled experience provided evidence that the
      envelope technique for opening of the anterior capsule does not ensure sufficient
      stability of these lenses in the later stage and their decentration may cause
      serious complications. Therefore the optimal solution is to place the implant in
      the capsule after circular capsulorhexy. Improvement of the geometrical and optic
      properties of the lenses during the subsequent follow-up and their perfect
      harmony with the surgical technique will produce even better functional results
      in operated patients.

PMID- 1394521
TI  - [A method for determining peroperative centering and monitoring the development
      of postoperative decentration of intraocular lenses].
AB  - After implantation of intraocular lenses (IOL) Purkinje images 3 and 4 (Pi3 and
      Pi4) are clearer on the anterior and posterior surface of its optical part
      (subsequently only lens). Along with the corneal Pil this phenomenon was already
      used in clinical work for more accurate calculations of the degree of
      decentration and tilt of the lens in the eye. The authors describe a simplified
      method for assessment of the position of the lens by means of Pil, 3 and 4, using
      apparatuses with an approximately coaxial light. The method uses overlapping of
      Pi1, 3 and 4 in perfect centering of the lens in the axis of the eye (it is
      assessed by drawing a perpendicular line on the centre of the cornea) and marked
      dislocation of Pi3 in the direction of decentration of the planoconvex lens with
      the convexity facing the cornea. The inclination of the lens must be eliminated
      according to positions Pi1 and Pi4. The method is suitable for peroperative
      centering and for assessment of the direction and extent of decentration of these
      lenses. The authors discuss the possible use of this method also in biconvex and
      planoconvex lenses with the convexity facing the retina. In a group of 10
      implanted planoconvex lenses the authors demonstrate the possibility of perfect
      peroperative centring of the lens and other applications of the method. Incorrect
      position of the IOL at the end of the operation, which can be one of the factors
      of later complications, did not change during the early postoperative period.

PMID- 1394522
TI  - [Analysis of the first 1000 implants of intraocular lenses].
AB  - The authors give an account of the development of implantology and extracapsular
      extraction in their department. In 1987 they performed 342 operations of
      cataract, an intraocular lens was implanted in 13.2%, extracapsular extraction
      was performed in 12.9%. In the first half of 1991 354 operations of cataract were
      performed, an intraocular lens was implanted in 82.5%, and extracapsular
      extraction was performed in 96.9%. The most frequent peroperative complication
      was rupture of the posterior capsule--from 14.0% to 20.1%. The most frequent
      postoperative complication (306 implantations in the first half of 1991)-
      keratopathia striata 179, fibrinous exudate--79, elevated intraocular pressure-
      50. The time spent in hospital in the first half of 1991 was on average 2 days in
      156 operated patients who did not develop any or only one postoperative
      complication. The most frequent postoperative complication was posterior capsule
      opacification--11%. The most serious late complication during the entire follow
      up period was endo-ophthalmitis in 8 eyes which in 5 patients after an interval
      up to 12 months following operation ended by evisceration of the bulbus--in all
      instances Russian lenses which were sterilized by ourselves were involved. The
      visual acuity on admission was below 6/60 in 72.3%, on discharge 6/12 or better
      in 32.8% and 6 months after operation 6/12 or better in 73.9%, incl. 651 eyes
      (88%) without supplementary correction. Despite the difficult conditions
      extracapsular extraction with implantation of an intraocular lens has become a
      routine method in our department, with a short period of hospitalization and
      minimal contraindications.

PMID- 1394523
TI  - [The individual A constant in the SRK II formula].
AB  - The authors investigated the postoperative dioptric deviation from the calculated
      optic power of emetropic intraocular lenses by means of the formula SRK II
      without and with use of the individual regression constant A. Within the range of
      +/- 1.5 D the deviation varied for both methods in 87.7% of operated eyes;
      between -1.0 and +1.0 D the percentage of dioptric deviations without
      personalization was 66.2 and with the use of the individual constant A it was
      73.8.

PMID- 1394524
TI  - [Determination of correction based on natural visual acuity in myopes].
AB  - The authors demonstrate the possibility to assess the correction in ametropes
      according to the value of their natural vision. To this end they use normalized
      optotype tables with Landolt rings which have a constant diminution coefficient
      between individual consecutive lines. By means of this elaborated method the
      authors were able to assess in twenty myopic subjects that a correction of -1.0
      corresponds to an improvement by four lines, one line thus corresponds to a
      correction of -0.25 dioptres.

PMID- 1394525
TI  - [Isolation of Dirofilaria repens in vitreoretinal findings].
AB  - The authors present the case of a 18-year-old patient who reported deteriorated
      vision and mobile dark shadows on the left eye. Examination revealed in the
      vitreous body an extremely mobile filiform, worm-like formation, white in colour,
      of the size of an arteriole, about 9 mm long. In the course of hospitalization
      the formation was isolated by surgery of the pars plana vitrectomy and subjected
      to detailed helminthological examination. The worm was identified as Dirofilaria
      repens (Reillet et Henry 1911) and described in detail. The presented finding is
      the first finding of this parasite in this country and at the same time the first
      finding of this parasite in Czechoslovakia.

PMID- 1394526
TI  - [Retinal detachment with retinal dialysis].
AB  - A group of 165 eyes operated on account of detachment of the retina comprised 16
      eyes with oral dialysis (i.e. 9.7%). Only in 6 eyes of the group there was a
      positive traumatic case-history. The anatomical results of the operations were
      favourable (81% amotions cured), the functional results depended on the state of
      the macula before operation.

PMID- 1394527
TI  - [5 years' experience in the treatment of neovascular glaucoma using
      cryocoagulation. I. Development of intraocular pressure].
AB  - The authors evaluate the results of reduction of intraocular pressure in 38 eyes
      with neovascular glaucoma after a cryosurgical operation. In 12 eyes they used
      cyclocryocoagulation as an independent method, in 26 eyes transscleral panretinal
      cryocoagulation combined with cyclocryocoagulation in one session. The achieved
      results indicate, that intraocular pressure in neovascular glaucoma can be
      influenced more readily by a combined cryosurgical operation than by
      cyclocryocoagulation alone. When using transscleral panretinal cryocoagulation in
      combination with cyclocryocoagulation, they achieved after operation an
      intraocular pressure under 26 mm Hg within 3 days after operation in 50%, within
      10 days in 76.9%. They observed a subsequent rise of the intraocular pressure in
      15%. Hypotension developed in 30.8%. A quite high percentage of eyes with extreme
      hypotension and subsequent atrophy of the bulbus with amourosis (27%) is
      according to the authors due to too extensive cyclocryocoagulation.

PMID- 1394528
TI  - [5 years' experience in the treatment of neovascular glaucoma using
      cryocoagulation. II. Treatment of pain and the development of visual acuity].
AB  - The authors evaluate the therapeutic results of pain of the eyes and the
      development of visual acuity of 38 eyes with neovascular glaucoma treated by
      cryocoagulation. In 12 eyes they used cyclo-cryocoagulation as an independent
      method and in 26 eyes the method of transscleral panretinal cryocoagulation
      combined with cyclo-cryocoagulation. The authors did not find a correlation
      between the degree of increased intraocular pressure and the painfulness of the
      eye. In the treatment of pain they achieved markedly better results when using
      transscleral panretinal cryocoagulation than cyclo-cryocoagulation alone. The
      better therapeutic results of treatment of pain by combined cryosurgery is
      associated with a better compensation of intraocular pressure. In the authors'
      view a significant in the treatment of pain is also played by the newly described
      so-called analgetic effect of panretinal cryocoagulation which develops probably
      as a result of damage of sensitive nerves of the bulbus during freezing of the
      sclera and the choroid. The development of the so-called analgetic effect is
      probably associated with two facts: relief from severe pain was perceived also by
      patients where during the early postoperative period a high intraocular pressure
      still persisted and also in patients where a high intraocular pressure rose
      again. This condition was, however, as a rule not associated with the onset of
      new pain. The use of transscleral panretinal cryocoagulation combined with cyclo
      cryocoagulation achieved regression of pain within 5 days after operation in
      100%. The author provide evidence that the visual acuity in neovascular glaucoma
      recedes very rapidly and irreversibly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394530
TI  - [Rhabdomyosarcoma of the orbit].
AB  - A twenty-eight year-old female patient developed within one week a protrusion and
      deviation of the eyeball associated with pain and loss of vision. The sudden
      development, atypical course, obscure clinical picture suggest rather an
      inflammatory or vascular affection in the orbit; only subsequent development
      confirms the development of a malignant process in the orbit.

PMID- 1394529
TI  - [Use of 5-fluorouracil in complicated cases of glaucoma--personal experience].
AB  - The authors give an account of the results of trabeculectomy with the use of 5
      fluorouracil in a group of 8 patients with complicated glaucoma. Treatment was
      successful in 5 patients, in three patients it failed. The use of 5-fluorouracil
      in specific cases of glaucoma gives greater hope of successful surgery.

PMID- 1394531
TI  - [Therapeutic and cosmetic effect of cryocoagulation therapy of basaliomas in the
      area of the eye].
AB  - The authors evaluated the results of cryosurgical intervention in a group of
      patients with advanced basaliomas with surgically adverse localizations from the
      aspect of relapses and the cosmetic effect. Due to the simple procedure and
      achieved effect this technique is a considerable asset.

PMID- 1394533
TI  - [Calculation of the optic power of implants and errors in calculation].

PMID- 1394532
TI  - [Betoptic, a new possibility in the treatment of glaucoma].
AB  - The authors present an account of their findings in connection with a new
      selective beta 1 adrenergic antagonist in the preparation Betoptic. They compared
      its effect on intraocular pressures, pulse rate, systemic blood pressure and
      vital capacity of the lungs in ten patients with primary open-angle glaucoma with
      the effect of Timoptol and placebo in equally sized groups. They found that the
      preparation reduces reliably the intraocular pressure, it does not reduce the
      pulse rate and does not influence the vital capacity and systemic blood pressure.
      They did not detect any local or general undesirable effects. It can be therefore
      used even in subjects where unselective beta blockers are contraindicated or
      poorly tolerated.

PMID- 1394534
TI  - [Electrophysiology of the retina].

PMID- 1394535
TI  - [Surgical treatment of strabismus in children (a 12-year study)].
AB  - A group of 2205 operations of strabismus in the course of 12 years reveals a
      clear predominance of operations of dynamic strabismus (94%), as compared with
      surgery of paralytic strabismus and ocular torticollis on account of nystagmus
      (6%). This fact provides evidence of a marked ratio of a non-paralytic aetiology
      of strabismus in the child population. In esotropia, the most frequent type of
      strabismus, the authors consider as most suitable the technique of weakening of
      the inner rectus muscles by a dosed elongation according to Gonin-Hollwich, as
      compared with the classical retroposition of this muscle. In exotropia the
      authors recommend reinforcing operations only or in combination with a weakening
      operation of the rectus muscles. The gradual development of application of the
      technique of surgery of the hyperfunctional lower oblique muscle is in favour of
      treble partial myotomy (elongation). They operate paretic strabismus when the
      IIIrd, IVth, VIth nerve are affected and supranuclear paresis of the levators by
      a complex procedure incl. transposition operations of the functional muscles. The
      authors operate ocular torticollis after a careful analysis of the congenital
      nystagmus, using special techniques on the rectus and oblique muscles which
      adjust the position of the head and bulbs.

PMID- 1394536
TI  - [Bone age of preschool children in Eastern Slovakia].
AB  - The authors present the results of evaluation of the skeletal maturation in 579
      children aged 1-5 years. Bone maturation was evaluated, based on skeletal age, by
      the Tanner-Whitehouse II method (Tanner et al., 1975). It was found that girls up
      to the age of three years had lower and in the more advanced age groups higher
      values of skeletal age than boys. Boys were retarded as regards skeletal age in
      relation to chronological age on average by 0.28 years and girls by 0.25 years.

PMID- 1394537
TI  - [Personal experience with genetic study of the hearing-impaired].
AB  - In 1988-1990 the authors examined on account of impaired hearing in the family 78
      families, which were divided into two groups. The first group comprises 48
      families of actively invited pupils from schools with children with impaired
      hearing in Prague, the second group comprises 30 families examined in the
      framework of common counselling and consultation services. On the first group a
      genetic aetiology of the disorder was revealed in 75% and in the second group in
      73.3% of the cases. An autosomal recessive type of heredity was proved
      unequivocally in 31.3% in group 1 and in 20.0% in group 2. An autosomal dominant
      type of heredity was found in 6.25% in group 1 and in 6.7% in group 2. X-linked
      deafness was proved only in group 1 in 4.2% and sporadic syndromes only in group
      2 in 13.3%. In 33.3% in both groups it was not possible to differentiate the type
      of heredity (most frequently the child and both parents were affected). In the
      first group three genetic syndromes were detected and in group 2 seven genetic
      syndromes. As the percentage of genetically conditioned hearing disorders in both
      groups is relatively high, the authors consider active screening of deaf children
      more useful so far.

PMID- 1394538
TI  - [Use of modern methods in prenatal diagnosis of congenital adrenal hyperplasia-
      examination protocol].
AB  - The prenatal diagnosis of congenital adrenal hyperplasia (CAH) in the second
      trimester of gestation (as done so far in this country) is late and unsuitable
      with regard to possible interruption of pregnancy. Modern methods of early
      prenatal diagnosis are based on examination of material from chorionic villi (6th
      10th week of gestation) or early amniocentesis (10th-12th week of gestation). The
      authors present their decision taking scheme, examination protocol and their own
      experience with the use of molecular genetic analysis and assessment of 17
      hydroxyprogesterone from early amniocentesis in the prenatal diagnosis of CAH.
      This procedure is a priority in this country.

PMID- 1394539
TI  - [A non-classic form of congenital adrenal hyperplasia].
AB  - The authors examined five children with the non-classical form of adrenal
      hyperplasia. The clinical symptoms of the disease comprise: early congenital
      pubic hair, small stature, accelerated bone maturation, infertility, in girls
      hirsutism, acne, menstrual disorders, amenorrhoea, in boys oligospermia, acne.
      Laboratory examination reveals slightly elevated 17-OH progesterone values during
      the synactene loading test. It is an autosomal recessively hereditary disease. It
      is due to an allelic variant of the gene for 21 hydroxylase. The authors revealed
      a link with antigen B14. Even in the small group examined antigen B14 was present
      in 40%, although the prevalence in our population is 2.9%.

PMID- 1394540
TI  - [Levels of plasma amino acids in normal neonates within the context of their
      postnatal adaptation].
AB  - The authors present values of plasma amino acid concentrations assessed on an
      automatic analyzer in a group of 12 mature neonates whose early and late post
      partum adaptation and subsequent psychosomatic development followed-up to the age
      of 18 months was normal. The amino acids were assessed at the time of delivery,
      during the maximal weight loss of the infant after the third day and the last
      estimation was made before discharge from the maternity hospital when the body
      weight curves of all infants had a rising trend. None of the infants had neonatal
      jaundice and all were discharged fully breastfed.

PMID- 1394541
TI  - [The effect of food supplementation with organically bound chromium on indicators
      of compensation in diabetic children and adolescents].
AB  - To the food of 33 diabetic patients typ I (in the age of about 15 years)
      organically bound chromium was added for 6 weeks. The influence on the metabolic
      compensation could not be proven, although in some individuals of this group the
      favorable effect of chromium can not be excluded.

PMID- 1394542
TI  - [Immunization against diphtheria and tetanus in children with severe neurological
      disorders].
AB  - In the clinical department of the Institute for Sera and Vaccines 260 children
      with serious neurological diseases were immunized with Alditeana and Alteana.
      After immunization an undesirable reaction was recorded in 3.1% of the immunized
      children. Mostly recurrence or potentiation of clinical manifestations of the
      basic neurological disease of the child was involved. Investigation of the
      anamnestic data revealed several serious undesirable reactions after vaccination
      with Alditepera in a health centre for child patients.

PMID- 1394543
TI  - [Ambroxol in the treatment of idiopathic respiratory distress syndrome].
AB  - The authors treated five premature infants with idiopathic respiratory distress
      syndrome with ambroxol, using its action on type II pneumocytes and thus also on
      surfactant formation. In all infants improvement of the clinical condition was
      achieved, no side-effects were observed.

PMID- 1394545
TI  - [Bronchologic examination].

PMID- 1394544
TI  - [Problems in child nutrition. 2. Nutrition in preschool-age and school-age
      children. Nutrition in children in families with different life styles].
AB  - The authors presents a review of the main principles of enteral nutrition of
      preschool and school children. He draws attention to the unsuitable character of
      an alternative diet for growth and development of the child. The nutritional
      status of children on an alternative diet can be, however, supplemented and
      modified.

PMID- 1394546
TI  - [Mild injuries of the head in 0-3-year-old children].
AB  - The authors discuss the problem of mild head injuries in children aged 0-3 years
      and based on data obtained by a retrospective examination of a group of 119
      hospitalized children and data in the literature they submit recommendations as
      regards examination and follow-up of these children.

PMID- 1394547
TI  - [Medullary carcinoma of the thyroid gland. Personal experience].
AB  - The authors present their experience with the diagnosis and treatment of
      medullary thyroid carcinoma (MTC) in a group of 175 patients in the records of
      the RI in Motol. From the above number 106 are alive, 69 of the patients who died
      were diagnosed at the time of the clinical manifestation of the disease,
      frequently an advanced stage of the disease. Of the living patients one third was
      treated by total thyroidectomy after active screening. MTC accounts under our
      conditions in recent years for 8.6% of all thyroid malignancies. The familial
      variant with autosomal dominant heredity accounts for 26.5% of the above number.
      Within the framework of the familial variant the most frequent finding is non-MEN
      MTC, only 30% MTC are part of the MEN 2A or MEN 2B syndromes. MTC in childhood
      belongs practically always to the familial variant. At present the authors' group
      comprises 13 children and adolescents under 18 years, incl. one boy with the MEN
      2B syndrome who succumbed to the disease. In 8 children based on active screening
      total thyroidectomy was indicated, incl. 5 patients were by histological
      examination only hyperplasia of the C-cells, i.e. a precancerous condition, was
      detected. After operation repeatedly in all these patients the level of
      immunoreactive calcitonin is low which indicates an excellent prognosis. The
      authors draw attention to the importance of active screening in families of all
      direct relations of the patient where MTC was diagnosed. Complete removal of
      thyroid tissue at the time of hyperplasia of C-cells or the presence of tumourous
      microfoci has a marked positive effect on the subsequent fate of the
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394548
TI  - [Extended classification of diabetic retinopathy in children and adolescents].
AB  - The authors submit their own modification of the classification of diabetic
      retinopathy elaborated on the background of several years experience with the
      examination of children and adolescents with insulin dependent diabetes. The
      extended classification pattern makes it possible to differentiate and classify
      more accurately even slight incipient changes detected by
      chromatooophthalmoscopy. The presence of microaneurysms reflects well the degree
      of retinal damage in early stages. Special attention must be paid to intraretinal
      microvascular abnormalities (IRMA). The classification pattern is presented in a
      table included in the text.

PMID- 1394549
TI  - [Occurrence of diabetic retinopathy in children and adolescents and its relation
      to the duration of diabetes and patient age].
AB  - In a retrospective investigation the authors give an account of a group of 302
      children and adolescents with insulin dependent diabetes (mean age 14.2 years,
      mean duration of diabetes 6.4 years) whom they examine regularly by
      chromatoophtalmoscopy and evaluate the findings according to their own extended
      classification of diabetic retinopathy. In 29% of the patients the finding was
      positive and in 25% the finding was suspect. The most frequent pathological
      change were microaneurysms; intraretinal microvascular abnormalities (IRMA) were
      detected in 13 patients. The trend towards proliferative changes is apparent in
      some patients surprisingly soon. The authors emphasize the sensitivity of the
      method which along with the extended classification of retinopathy makes its
      monitoring possible. The authors discuss the value of fluorescent angiography in
      the initial stages of retinal damage. They provide evidence of a statistically
      significant relationship of diabetic retinopathy and the duration of diabetes (p
      < 0.001) and age (p < 0.001).

PMID- 1394550
TI  - [Immunologic reactivity in children on a chronic dialysis program and after
      kidney transplantation].
AB  - Dialysis and transplantation of the kidney have become in Czechoslovakia part of
      routine therapy of chronic renal failure (ChRF) in children and adolescents. The
      authors examined 16 children aged 4-17 years (x = 10.5) treated in a chronic
      dialyzation programme (ChDP) by haemodyalisis and 20 children after
      transplantation of a cadaverous kidney, age 4.5-16.5 years (x = 11.5), incl. 14
      patients with a stable function of the graft and six patients during the period
      of acute rejection of the graft. The authors tested the basic parameters of
      humoral and cellular immunity in all three groups of children. In the group of
      the CRI a significant drop of the level was found only in serum IgA, the other
      parameters, incl. examination of sub-populations of lymphocytes CD3+, CD4+ and
      CD8+, did not differ significantly from normal values. In patients with a
      stabilized function of the graft treated by Cyclosporin A, prednisone, and in
      some cases also with azothioprim, the authors found a significantly lower
      absolute number of lymphocytes of the mentioned sub-populations as compared with
      controls and patients included in a ChDP. During the period of acute rejection
      the absolute number of CD3+, CD4+, CD8+ increased significantly, as compared with
      the period of stabilized function of the graft. Thus patients in CRI do not
      manifest despite the serious affection of the organism serious changes of immune
      reactivity within the scope of examinations made by the authors. Monitoring of
      immunity parameters in patients with transplants can contribute to evaluation of
      the effect of immunosuppression (it can draw attention to low dosage of drugs)
      and in the context with other clinical and laboratory examinations it can
      contribute to the diagnosis of acute rejection.

PMID- 1394551
TI  - [High frequency "bubble" oscillation ventilation in the neonatal period].
AB  - The authors tested their own high frequency, oscillation, "bubble" ventilator on
      a model of neonatal lungs in vitro and in vivo. They used the effect of
      oscillations which develop when through fluid (in vivo water) a mixture of air is
      bubbled and which can be, if the expiration tube is sufficiently rigid,
      transmitted back into the lungs. If the CPAP circuit is suitably arranged, it can
      ensure an adequate exchange of blood gases. The authors found marked changes in
      the amplitude of pressure oscillations as well as of the frequency in relation to
      the shape of the ending beneath the fluid surface (greatest when a funnel with a
      30 mm diameter and 90 degree angle in relation to a normal line projected on the
      water surface is used). They found that the compliance (C) has no substantial
      effect on the amplitude nor on the frequency of oscillations. The mentioned
      bubble system approached as to its efficiency the commercial oscillation
      ventilator Stephen 3000 SFH and was used in the therapy of respiratory failure in
      three neonates with body weights of 1250-2700 g. The authors conclude that high
      frequency oscillation "bubble" ventilation is a cheap, safe and highly effective
      therapy which can be used in any department providing care of neonates even
      during transport.

PMID- 1394552
TI  - [Present possibilities of early diagnosis of hearing disorders in children
      belonging to the youngest age groups].
AB  - In a great proportion of children loss of hearing originates during the neonatal
      period. It is assumed that of 1000 neonates some 6 to 16 children suffer from
      impaired hearing. By early detection of hearing loss during neonatal and infant
      age by appropriate treatment, rehabilitation and training it is possible to
      achieve optimal speech development as well as development of mental and somatic
      abilities and to ensure to these children an adequate role in society. Early
      detection of impaired hearing based on screening of risk children already during
      the neonatal period is based on the use a risk registry. At the same time it is
      important to make parents and paediatricians of the first line of contact
      familiar with developmental stages of hearing and speech during the first year of
      life. Risk children must be dispensarized and they must be objected to
      orientative examination of hearing by reflex audiometry and other screening
      methods incl. the method of assessment of evoked otoacoustic emission. By
      systematic screening is is possible to detect suspected loss of hearing in as
      many as 60% of risk children. To verify the suspect impaired hearing it is
      necessary to make an objective examination of hearing by a child
      otolaryngologist.

PMID- 1394553
TI  - [Variations in lipid metabolism in long-term monitoring of children treated for
      diabetes mellitus].
AB  - The authors investigated selected indicators of the lipid metabolism in 31
      children with insulin-dependent diabetes for a period of 3 to 14 years. They
      divided the patients into two groups those with a glycosylated haemoglobin below
      or above 9 mumol/1 g haemoglobin. They compared the assembled results of the two
      groups and also with the results obtained in a control group. The total
      cholesterol was in both diabetic groups higher than in healthy subjects and was
      higher than the value which is considered from the aspect of the genesis and
      development of atherosclerosis as a risk value. Children with poorly compensated
      diabetes, i. e. with a glycosylated Hb level above 9 mumol had a higher
      cholesterol level as compared with well compensated diabetic children. The pre
      beta fraction of lipoprotein increased in both groups of patients, however, more
      in those where the disease was not well compensated. There was a parallel
      decrease of the alpha fraction and the lipoprotein profile had a markedly
      atherogenic character. The apolipoprotein B concentration was in patients with
      well compensated diabetes lower, as compared with controls but in patients with
      poorly compensated diabetes after 4-5 years treatment is was significantly
      higher. Poor compensation of diabetes led after 4-5 years duration to a
      significant rise of the serum triglyceride level. As the blood lipid levels are
      influenced in a significantly way by diet, compensation of the disease and a low
      fat diet are essential with regard to the results assembled in this investigation
      for prevention of ischaemic heart disease in diabetic subjects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1394554
TI  - [Growth, weight and physical proportionality in twins].
AB  - The growth, weight and proportionality of twins aged 1-15 years from the South
      Moravian Region were studied and compared with a control population. The sample
      of twins was divided in three groups: identical twins, nonidentical like-sexed
      twins and boys and girls from the unlike-sexed pairs. No reasonable differences
      between twins A and B were observed, therefore they are not evaluated separately.
      All the twins were born in years 1973-1987, the total number was 2,226 boys and
      2,302 girls. A comparison with a control population revealed a lower mean height
      as well as weight of identical twins until the age of 15 years. The mean weight
      of identical twins was lower than that of nonidentical ones. Similar pattern were
      observed also in height, the statistical significance was found only in boys and
      only on a 5% level. Twins from unlike-sexed pairs were more like the control
      population than twins from unidentical like-sexed pairs, however, the differences
      in height in girls were not statistically significant. The distribution of
      proportionality values has shown an accumulation near zero--we can conclude that
      twins are more proportionate than other children of their age (i.e. less obese
      and less meagre). As expected, the observed intra-pair differences in identical
      pairs were significantly lower than in nonidentical like-sexed pairs.

PMID- 1394555
TI  - [Pulsed magnetic fields--their possibilities in pediatric neurology].
AB  - The author reviews information on the use of a pulsatile magnetic field with
      defined parameters in some child diseases of the CNS according to his experience
      assembled during the past five years. PMP was applied in 17 cases with spinal
      amyotrophy type M. Werdnig-Hoffman and in 16 cases with DMO. In both diseases
      treatment was previously only symptomatic. PMP frequencies of alpha EEG waves
      were used during application on the area of the head and a different frequency
      for whole body treatment focused on muscular dystonia. The author draws attention
      to the specificity of biotropic parameters of the applied magnetic field.

PMID- 1394557
TI  - [Prenatal diagnosis of congenital adrenal hyperplasia and possibilities of
      prenatal therapy].

PMID- 1394556
TI  - [New drugs in pediatric dermatology].

PMID- 1394558
TI  - [Duodenal atresia--evaluation of long-term results].

PMID- 1394559
TI  - [The "baby friendly hospital"--a new UNICEF/WHO initiative].

PMID- 1394560
TI  - [Commentary on the Report on Neonates].

PMID- 1394561
TI  - [Nephrotic syndrome in children. I. Incidence, pathogenesis, clinical aspects and
      morphology. II. Therapy, results and prognosis of the disease].

PMID- 1394562
TI  - [A brief description of methods for studying pulmonary function in children and
      adolescents].

PMID- 1394563
TI  - [Prevention of infective endocarditis as recommended by the Pediatric Cardiology
      Working Group].

PMID- 1394564
TI  - [Occurrence of allergic diseases in children with neonatal allergic exanthema].
AB  - In 1990 in the allergological ambulatory department for children in Trencin 263
      children were examined, born during the first half of 1981 and second half of
      1982 who suffered during the first days after delivery from exanthema allergicum.
      In 186 children i.e. 71%, by the age of 8 and 9 years late allergies developed.
      The authors investigate various factors in the prenatal, perinatal and postnatal
      period and compare possible relations with the development of late allergic
      manifestation in children with exanthema allergicum neonatorum.

PMID- 1394565
TI  - [Langerhans-cell histiocytosis in children].
AB  - Histiocytosis from Langerhans cells is a new term for a group of diseases
      formerly called histiocytosis X. In The Faculty Hospital Motol the authors
      treated between July 1974 and December 1980 84 children with this disease. Twenty
      one suffered from the malignant form (formerly Letterer-Siwe and Hand-Schuller
      Christian disease) and in 63 patients the diagnosis of eosinophil granuloma was
      established. In 21 children with unequivocally malignant disease the authors
      started chemotherapy immediately after establishment of the diagnosis and in six
      they indicated in addition radiotherapy. Of these 21 children 16 are in complete
      remission and 5 children died from progression of the disease during treatment.
      In the group of 63 children with eosinophil granuloma in 44 only excochleation of
      the focus was performed. Chemotherapy was administered to 12 children, incl. 5
      where it was combined with radiotherapy. A relapse of the disease was recorded in
      8 children. At present all patients suffering from the disease are in complete
      remission.

PMID- 1394566
TI  - [Transitory hyperphosphatasemia in childhood].
AB  - Transient hyperphosphatasaemia was detected in 11 children hospitalized at the
      First and Second Paediatric Clinic of the Paediatric Faculty Hospital in
      Bratislava in 1985-1990. The authors analyzed retrospectively 6 children from
      this group where it was possible to evaluate accurately the trend of serum
      alkaline phosphatase. In all children the high alkaline phosphatase activity was
      detected incidentally during the initial examination. The reason for
      hospitalization were in four instances respiratory infections, in one instance
      coeliac disease and in one instance infectious mononucleosis with infection of
      the urinary pathways. The maximum increase of serum alkaline phosphatase was 5-15
      fold higher than the upper borderline of the reference range for the given age
      group. The activity declined to normal spontaneously independently on the course
      of the basic disease and treatment, always in the course of 3-12 weeks. The
      isoenzyme pattern of alkaline phosphatase with a high ratio of the thermolabile
      isoenzyme was typical. Finally the authors emphasize that recognition of this
      obscure condition which does not endanger life can spare the children many
      unnecessary and expensive examinations.

PMID- 1394567
TI  - [Liver diseases in children with alpha 1-antitrypsin deficiency in infancy].
AB  - The authors evaluate the health status of children with alpha-1-antitrypsin
      deficiency, focused on liver disease in infant age. The children were selected by
      neonatal screening. Of 21 children one had severe neonatal hepatitis with
      progression to cirrhosis, 2 children had clinically apparent jaundice to the age
      of two months, 6 children had elevated total bilirubin and transaminase levels
      without clinical signs of the disease, 12 of the remaining children had no
      clinical and laboratory signs of liver disease. In the discussion the authors
      compare the results with data published abroad.

PMID- 1394568
TI  - [Carbocysteine in the treatment of recurrent bronchitis in infants].
AB  - In a group of 51 children aged 6-24 months the therapeutic effectiveness of the
      mucolytic preparation carbocysteine was tested and compared with the effect of
      Ipeca syrup. The effect was evaluated by means of a point score comprising
      changes of the clinical picture of the disease and the use of other laboratory
      examinations. The results of the examination revealed the more favourable effect
      of carbocysteine, as compared with a mixture of Ipeca syrup in the treatment of
      acute relapsing bronchitis in infants.

PMID- 1394570
TI  - [Sixth disease--exanthema subitum].
AB  - The author deals with the epidemiology of the sixth disease--exanthema subitum
      which is caused by the herpes virus hominis type 6. There are nine forms of the
      disease. The haemogram is characterized by granulocytopenia, eosinopenia with
      relative lymphocytosis, thrombocytopenia.

PMID- 1394569
TI  - A case of hyperplasia of the anterior lobe of the pituitary imitating intrasellar
      expansion.
AB  - The authors describe the case of an obese girl with severe hypothyroidism which
      led to increased TSH secretion and finally to hyperplasia of the anterior lobe of
      the pituitary diagnosed by magnetic resonance. After substitution treatment with
      thyroid hormones was started, marked improvement of the general condition, loss
      of body weight and normalization of laboratory findings and regression of
      hyperplastic tissue occurred.

PMID- 1394571
TI  - [Multiple (serial) poisoning with scopolamine present in a compounded nose drop
      preparation].
AB  - The authors describe three cases of scopolamine intoxication which was added to
      nasal drops instead of Mucoseptonex. An account is given of the characteristics
      of scopolamine intoxication and of possible therapy.

PMID- 1394572
TI  - [Food allergy and associated diagnostic and therapeutic problems].

PMID- 1394573
TI  - [Diagnostic criteria for juvenile chronic rheumatoid arthritis].

PMID- 1394574
TI  - [Trends in pediatric and infant demographic indicators in 1991].

PMID- 1394575
TI  - HIV infection and nursing students.

PMID- 1394576
TI  - [The capacity of IL-2 production of peripheral blood lymphocyte in patients with
      pneumonia].
AB  - The capacity of IL-2 production of peripheral blood lymphocyte (PBL) were
      determined in 54 patients with pneumonia in acute stage (23 cases of 20-57 years
      old and 31 cases over 60 years old) and 33 cases in convalescent stage. 20
      elderly COPD in remission patients and 59 healthy control (32 aged 20-55 and 27
      over 60) were determined also. It was shown that the capacity of IL-2 production
      of the patients with pneumonia in acute stage were markedly lower than healthy
      control (P less than 0.01), and that of the elderly patients' were markedly lower
      than elderly COPD patients also (P less than 0.01). The IL-2 level were also
      lower in the patients with pneumonia in convalescence than in the healthy control
      (P less than 0.01). The capacity of IL-2 production of elderly COPD patients and
      healthy elderly donors were at the same level (P greater than 0.05), both of the
      two groups' IL-2 level were significantly lower than that of the healthy young
      middle age donors. It was suggested that the lowered immune function may be one
      of the important factors causing the COPD patients and the elderly people
      susceptible to infection, and it may be one of the important causes of the more
      severe condition and protracted course in elderly patients.

PMID- 1394577
TI  - [A primary study on the relationship between the acute infection of chronic
      obstructive pulmonary disease (COPD) and mycoplasma pneumoniae].
AB  - The specific antibodies of Mycoplasma Pneumoniae (MP) in the sera of 227 normal
      adult controls and 187 adult patients with acute infections of COPD were measured
      by immunofluorescence assay (IFA). The findings showed: 1. in the sera of control
      group, the titer of specific IgM antibody of MP were lower than 1:8 in 224 cases
      (98%) and the specific IgG antibody were below 1:16 in 218 cases (96%). 2.
      Positive results for MP antibodies (the IgM 1:8 or/and the IgG 1:16) were found
      in 70 cases (37.4%) of adult patients with acute infections of COPD. We suggest
      that Mycoplasma Pneumoniae is a common pathogen for the adult acute infections of
      COPD.

PMID- 1394578
TI  - [Pulmonary Aspergillus infection. A study of 61 cases of clinical, roentgenologic
      and pathological findings].
AB  - The clinical results of 61 patients with pulmonary aspergillosis were analysed.
      Patients were admitted since 1975 to 1989. Pathologic evidences were obtained at
      postoperation in 51 patients. The main clinical symptom was hemoptysis, and was
      frequently misdiagnosed as pulmonary tuberculosis, bronchiectasis or other
      pulmonary disease. The diagnosis and treatment of pulmonary aspergillus infection
      was discussed.

PMID- 1394579
TI  - [Pathological changes in the trachea after tracheostomy in patients with
      respiratory failure].
AB  - A variety of pathological changes in trachea were observed in 7 cases with
      tracheostomy. The common lesions were inflammation, necrosis and ulcer, and
      squamous metaplasia or granuloma were seen in those with tracheal tube for longer
      time. The dilatation of trachea was manifested by dislocating of the tube and not
      sealing of the cuff. Cuff-radiography could show the site and degree of the
      dilatation of trachea. In order to alleviate the lesions, the tubes made of
      plastic or silica gel with lower pressure cuff were recommended. The prevention
      of local infection and improvement of nutritional status were also important.

PMID- 1394580
TI  - [A study on the functional condition of airway muscarinic M2-receptors in
      asthma].
AB  - We investigated the hypothesis that airway M2-receptor selectively pretreated
      with aerosolized pilocarpine would modify the bronchoconstrictor response to
      histamine, which is, in part, vagally mediated. On two different days, the
      following two histamine inhalation challenges were performed in 12 normal
      individuals and 13 stable asthmatics: histamine alone or pilocarpine-histamine.
      In normal subjects, prior M2-receptor stimulation with pilocarpine suppressed the
      subsequent bronchial response to histamine. In asthmatic patients, however, prior
      pilocarpine exposure failed to modify the bronchial response to histamine. The
      results suggest that prior M2-receptor stimulation has a protective effect on
      histamine induced bronchoconstriction in normal subjects and the absence of this
      inhibitory effect in asthmatic patients may represent the existence of functional
      depression of M2-receptors in asthmatic airways.

PMID- 1394581
TI  - [The effect of grain dust on non-specific bronchial hyperreactivity].
AB  - 246 grain elevator or mill workers were divided into heavy-exposure group and
      light-exposure group and methacholine provocation tests, were carried out. After
      provocation test, FEV1, FVC, MMEF, PEF, V50 and V25 significantly decreased in
      heavy exposure than those in light exposures. (P less than 0.01). 18.9% of heavy
      exposure was associated with bronchial hyperreactivity, which was significantly
      higher than that of light-exposure (4.4%). The incidence of more than 10%
      declines in FVC or FEV1 and 25% in PEF or V25 during one day or one week work
      shift was significantly higher in workers with bronchial hyperreactivity than in
      those without bronchial hyperreactivity (P less than 0.01). The findings
      indicated that exposure to heavy concentration of grain dust for long period can
      impair pulmonary function and cause nonspecific bronchial hyperreactivity.

PMID- 1394582
TI  - [The treatment of bronchiectasis by using left lower lobectomy with extirpation
      of lingular division of the bronchi].
AB  - 7 cases with bronchiectasis of left lower lobe and lingular segment were treated
      with left lower lobectomy and extirpation of the bronchi of lingular segment. Its
      advantages are that the upper division lung will not be damages, the complication
      of sigmentectomy be avoided. Meanwhile, the ability of lung expand will be
      remained and the compensating emphysema were prevented in the survival lung. In
      addition, the operating indication and method were discussed.

PMID- 1394583
TI  - [Studies on whole chromosomal DNA probes from Mycobacterium tuberculosis and
      Mycobacterium intracellulare].
AB  - The whole chromosomal DNA probes prepared from M. tuberculosis and M.
      intracellulare were used to hybridize in DNA dot blot and bacterial dot blot
      hybridization with 9 reference strains of Mycobacteria, including M.
      tuberculosis, M. bovis, M. avium, M. intracellulare, M kansasii, etc. These two
      probes showed good sensitivity and specificity for M. tuberculosis complex and M.
      avium complex respectively. Using the colony hybridization in situ, we can detect
      and identify M. tuberculosis with the probes on NC membrane after 1-2 week
      incubation over 7H9 agar plate.

PMID- 1394584
TI  - [The study of interleukin-2 and interleukin-2 receptor in patients with pulmonary
      tuberculosis].
AB  - IL-2 level and IL-2R expression of peripheral blood lymphocytes (PBL) were
      measured in 25 patients with type III and advanced tuberculosis (TB). The results
      showed that IL-2 level in patients was lower than that in controls, and that in
      the patients whose history of TB was over 3 years was significantly lower than
      that in the patients whose history of TB was within 3 years; There was no
      significant difference between the IL-2R expression on unstimulated PBL from
      patients and controls. IL-2R expression in PHA-stimulated PBL after culturing 72
      hours in patients was significantly lower than that in controls, and that in the
      patients over 3 years was significantly lower than that in the patients within 3
      years. The data indicated that the function of T helper cells in patients with TB
      was impaired, and the impairment was more serious in the patients with longer
      illness.

PMID- 1394585
TI  - [The diagnosis of smear negative pulmonary tuberculosis in superior segment of
      lower lobe].
AB  - 20 cases of tuberculosis in the superior segment of the lower lobe of the lung
      were misdiagnosed as lung cancer, pneumonia, bronchiectasis and inflammatory
      pseudoneoplasm were reported. The final diagnosis were confirmed by fiberoptic
      bronchoscopy (FOB). The causes of the misdiagnoses were: (1) the hilar mass
      shadow found on the PA chest film, mistaken for central type lung cancer; (2) the
      mass shadow found on the lateral chest film, mistaken for peripheral lung cancer;
      (3) the patients with fever, cough and expectoration accompanied by exudative
      infiltrative shadow, mistaken for pneumonia; (4) patients with recurrent attacks
      of hemoptysis but the lesions overshadowed by the spinal column on the lateral
      chest film were misdiagnosed as bronchiectasis. The author suggested PA and
      lateral chest films taken simultaneously were needed. The special points, to
      which should be pay attention during reading the films were listed and noted. FOB
      examination including TBLB, brushing and BALF for pathologic and AFB
      determination could be of help to confirm the diagnosis.

PMID- 1394586
TI  - [Clinical analysis of chronic renal function failure accompanied by pulmonary
      tuberculosis].
AB  - In 592 patients with chronic renal function failure (CRFF), 31 were accompanied
      by pulmonary tuberculosis, the incidence was 5.2%. The incidence of the First
      Affiliated Hospital of Sun Yat-sen University (6.6%) is higher than that of Zun
      Yi District Hospital (3.9%). The difference may be associated with dialysis
      therapy and regional TB natural population incidence. The data also showed that
      accompanied TB may be a reversible factor of deteriorating CRFF. Details of
      diagnosis and treatment of CRFF accompanied by TB are presented.

PMID- 1394587
TI  - [High-frequency chest wall oscillation].

PMID- 1394589
TI  - [CT studies on obstructive sleep apnea syndrome].
AB  - To ascertain whether there are structural and functional changes in the upper
      airway of obstructive sleep apnea syndrome (OSAS) pts. We studied 33 pts of OSAS
      with positive polysomnographic tests, 14 pts of non-apnea snore with negative
      polysomnographic tests, and 18 normal subject by using CT scanner (Somatom Dr 3).
      The results are as followings 1. There were narrowing region in the upper airway
      in OSAS pts and the non-apnea snore pts. Most of the narrowings were located at
      the level of oropharynx, which was correspondent to the level of the soft palate
      and the uvula. The length of the soft palate and the pre-spinal soft tissue
      thickness of two groups of pts were larger than non-snore individual. 2. The
      pharyngeal compliance was significantly higher in OSAS pts than in non-apnea
      snore pts. 3. There was no localised deposition of fat tissue surrounding the
      lumen of upper airway. 4. CT scanning is the non-invasive and more useful
      procedure for the diagnosis of OSAS and also would help to select the pts for
      surgery.

PMID- 1394588
TI  - [Rapid diagnosis of pulmonary Pseudomonas aeruginosa infections by indirect
      immunofluorescent antibody].
AB  - 167 sputum specimens collected from patients with pulmonary infection were tested
      by IFA (Indirect immunofluorescent antibody-staining) with serogroup-specific
      monoclonal antibody to Pseudomonas aeruginosa, compared with quantitative sputum
      culture. The results showed the minimum concentration of bacteria detectable by
      IFA was 10 cfu/ml. 31(86.1%) were positive in 36 specimens with more than 10
      cfu/ml of Pseudomonas aeruginosa. 22(100%) were positive in 22 specimens with
      more than 10 cfu/ml of Pseudomonas aeruginosa. In 127 specimens with a negative
      culture for Pseudomonas aeruginosa, 121(95.2%) were negative, 6(4.8%) were false
      positive which could be identified by Gram's-staining. The type of Pseudomonas
      aeruginosa could also be identified within 3 hours.

PMID- 1394590
TI  - [Effect of enoxacin on theophylline pharmacokinetics].
AB  - The effect of a multiple-dose regimen of oral Enoxacin on Theophylline
      pharmacokinetics was evaluated in 10 hospitalized patients with COPD. It was
      found that mean Theophylline concentrations in serum significantly increased 144%
      (P < 0.01), AUC increased 350.4% (P < 0.01), T1/2K increased 204% (P < 0.01),
      clearance decreased 76.8% (P < 0.01) during coadministration of enoxacin than
      before. This results suggested that a multidose regimen of enoxacin significantly
      slowed the clearance of theophylline and elevated theophylline concentrations in
      serum. The careful monitoring of serum theophylline level and modification of
      theophylline dosage in patients receiving enoxacin and theophylline were
      recommended.

PMID- 1394591
TI  - [Current status of the treatment of spontaneous pneumothorax in Japan].

PMID- 1394592
TI  - [The third nationwide random survey for the epidemiology of tuberculosis in
      1990].
AB  - The third nationwide epidemiological survey for tuberculosis covered 29
      provinces, municipalities and autonomous states in the Country. A total of 928
      survey points were surveyed. The results of the survey showed the following
      facts: The prevalence of pulmonary tuberculosis (radiological active) was
      523/100,000 population; the smear-positive prevalence was 134/100,000; The
      mortality of tuberculosis was 21/100,000; The tuberculous death ranked the
      seventh among ten leading causes of death. The results of the survey also showed
      that the decline of the magnitude of tuberculosis was so slow. The decline of the
      magnitude of tuberculosis in the coast provinces were much faster than the inland
      and remote provinces and it was faster in cities than in rural areas.

PMID- 1394593
TI  - [Application of enzyme linked immuno-electrophoresis for the diagnosis of
      tuberculosis].
AB  - The technique of Enzyme linked immuno-electrophoresis (ELIEP) was established to
      detect the specific antibody against tubercle bacilli. The results of 730 cases
      showed that the sensitivity of this method is 97.33%, and the specificity, 97.5%.
      Thus this method is more sensitive than the ELISA methods which had bean
      published. The manipulation of ELIEP is simple, convenient, and fast, reagent
      stable. This method may be used in diagnosis of tuberculosis with reliability and
      efficiency.

PMID- 1394594
TI  - [An analysis of lymphocyte subsets and purified protein derivative-antibody in
      pulmonary tuberculosis].
AB  - The lymphocyte subsets and PPD-antibody in peripheral blood were determined in 72
      cases of bacteriological positive pulmonary tuberculosis using monoclonal
      antibody to anti-T lymphocyte and ELISA assay. The results showed that the
      percentage of T3 was 52.44 +/- 11.46% and the OD of PPD-antibody was 0.47 +/-
      0.27 in initially treated patient group; 40.27 +/- 7.81%, 0.81 +/- 0.17 in
      chronic carrier group respectively. There were statistically significant
      difference between the two groups (P < 0.01). The percentage of T3 was
      significantly larger in 30-59 yr group than in more than 60 yr group among non
      chronic carriers (55.9 +/- 11.3% vs 44.4 +/- 2.4, P < 0.05). PPD-antibody was
      strongly associated with extent of lesion in lung.

PMID- 1394595
TI  - [Arteriography and bronchial artery embolization for massive hemoptysis in 100
      cases of tuberculous].
AB  - Bronchial arteriography and embolization with sponge gelatin were performed in
      100 tuberculous patients of massive hemoptysis. Three direct signs and other six
      indirect ones were found in arteriographies, Those signs were roentgenographic
      abnormalities for defining bleeding sites. 100 massive hemoptysis cases were
      treated with sponge gelatin embolization in bronchial artery. The results are
      satisfactory, the success rate were 92.9%, 87.4% and 79.0% at one week, one month
      and three months respectively. The advantages of arterial embolization and the
      reasons of failures were discussed in this paper.

PMID- 1394596
TI  - [Evaluation of the treatment of adult tuberculous meningitis].
AB  - Through analysis of the treatment in 205 patients of adult tuberculous
      meningitis, we considered: 1. effective and vigorous alleviation of high
      intracranial pressure in early stage, 2. appropriate dosage of corticosteroids
      and, 3. correct selection of antituberculous drugs was the mainstay for
      chemotherapy of tuberculous meningitis. The results were 82 patients (40.0%) were
      cured, 101 cases (49.3%) improved, 15 cases (7.3%) died and 7 cases (3.4%) had
      complications. 175 cases have been followed-up from two to five years, all of
      them are alive.

PMID- 1394597
TI  - [Experience of focal debridement in the treatment of tuberculosis of lumbar
      spine].
AB  - Experiences of 882 cases with tuberculosis of lumbar spine treated by focal
      debridement during 1956-1986 all patients survived the operation and 661 patients
      were cured in our department were reported. The relationship between chemotherapy
      and focal debridement was discussed. The selection of the appropriate time for
      this operation and important points to which attention should be paid during
      operation were described in detail.

PMID- 1394599
TI  - [Changes and significance of chemiluminescence of polymorphonuclear leukocytes in
      endotoxin-induced lung injury in conscious sheep].
AB  - The chemiluminescence (CL) of polymorphonuclear leukocytes and its relation with
      pulmonary microvascular permeability after endotoxin-induced lung injury in
      conscious sheep with lung lymph fistula were observed. Four hours after the
      injury the CL of PMNs increased from 0.27 cpm/PMN of baseline to 0.69 cpm/PMN (P
      < 0.05). The increment of the CL had positive correlation with the increment of
      lung lymph flow or permeability index (r = 0.632 0.638 P < 0.05), suggesting that
      the increase of pulmonary microvascular permeability after the endotoxin injury
      had relation with the increase of the respiratory tract of PMNs.

PMID- 1394598
TI  - [The pathological changes in pulmonary vessels complicated by cirrhosis with
      anatomicopathological analysis of 30 cases].
AB  - The pulmonary sections HE stained in 30 autopsy cases of cirrhosis were randomly
      reexamined. The distribution and degeneration of pulmonary arterioles and venules
      which were at alveolar level and the diameter of capillaries were observed; 10
      autopsy cases of other diseases were examined as control. The results showed
      tricuspid orifices were dilated in 20% of autopsies; Both lungs were heavier than
      those in the control group, pulmonary congestion were in 100% of autopsied lungs.
      Pulmonary artery degeneration occurred in 16.6%, the number of pulmonary
      arterioles increased in 73.0%, the hypertrophic dilatation and increasing number
      of pulmonary arterioles in 33.3%; local spider in pulmonary pleura in 20%. We
      conclude that above findings will be helpful to the indirect diagnosis of intra
      pulmonary shunt and pulmonary hypertension.

PMID- 1394600
TI  - [Changes in activity of phospholipase A2 and its metabolic production of
      prostaglandins in lung tissue of asthmatic guinea pigs].
AB  - The activity of phospholipase A2 and its metabolic production-prostaglandins were
      examined in lung tissue of allergic asthmatic guinea pigs. The results shows that
      the activity of phospholipase A2 after three days of asthma attack was raised
      54.19% than that of control group (P < 0.01), and decreased 69.27% when protected
      with chloroquine before asthma, and decreased 65.98% when only given chloroquine
      as a control; the ratio of those prostaglandins was resumed to control group when
      previously given chloroquine in asthma and normal guinea pigs. These results
      suggest that the activity of phospholipase A2 and changes of prostaglandins in
      lung tissue were related to allergic asthma of guinea pigs, the increase of TXB2
      or PGF2 alpha and decrease of PGE2 or 6-Keto-PGF2 alpha in lung tissue after
      three days of asthma attack may have a correlation with allergic asthma in guinea
      pigs.

PMID- 1394601
TI  - [Qualitative and quantitative observations of smoking-induced morphologic changes
      in muscular pulmonary arteries].
AB  - Light microscopy, transmission electron microscopy, image processing and
      morphometric technique were applied to analyze the morphologic changes in the
      muscular pulmonary arteries from the rats after exposure to smoking. The results
      showed that the pronounced muscularization of the small pulmonary arteries.
      significant reduction of the intraacinar arteries, intimal and medical thickening
      that was significantly associated with the cellular elements and extracellular
      matrix, and the smooth muscle cells proliferated and migrated from the media to
      intima of artery, the cell shape modified and increased in rough endoplasmic
      reticulum also were found. Although the functional significance of these findings
      is unknown, they might play an important role in smoke-induced occurrence and
      development of pulmonary hypertension and cor pulmonale.

PMID- 1394602
TI  - [Short-term effect and the mechanism of radix Angelicae on pulmonary hypertension
      in chronic obstructive pulmonary disease].
AB  - The changes of hemodynamics, hemorheology and blood gas were investigated in 28
      stable COPD patients with pulmonary hypertension after short-term treatment by
      Radix Angelicae. The level of TXA2, PGI2 were measured in 10 of the 28 patients
      before and after treatment. The results show that Radix Angelicae produced
      significant improvement on pulmonary hypertension, blood viscosity, hematocrit
      and the level of TXA2 decreased significantly. But the blood gas, blood pressure
      and the level of PGI2 remained unchanged in all of the patients.

PMID- 1394603
TI  - [Changes in acetylcholine and acetylcholinesterase in blood during pulmonary
      hypertension].
AB  - Two models of pulmonary hypertension in rats have been made with either
      monocrotaline or passive smoking (with or without infection). The decrease of RBC
      acetylcholinesterase activity and the increase of acetylcholine content in blood
      were detected in both rat models, but did not in rats which were only once
      infected by E. Coli, and the pulmonary pressure of the latter did not raise
      either. Comparing 30 cases of acute attack period of chronic pulmonary heart
      disease with 30 cases of normal persons, RBC acetylcholinesterase decreased
      significantly, indicating that hyperfunction of cholinergic nerve existed in
      pulmonary hypertension and pulmonary heart disease.

PMID- 1394604
TI  - Influence of circadian light-dark alternations on macrophages and lymphocytes of
      CBA mouse.
AB  - The influence of circadian 12 h light-12 h dark alternations on CBA mouse
      macrophages and lymphocytes was determined using tests for macrophage spreading
      and ingestion ability or flow cytometry immunophenotyping of blood, lymph node,
      and spleen lymphocytes. The animals were tested every 4 h around the clock.
      Collected macrophages were incubated in vitro for 3 or 18 h. Monoclonal
      antibodies permitted detection of T-lymphocytes, suppressor-cytotoxic T
      lymphocytes, helper-inducer T-lymphocytes, or B-lymphocytes. Two types of
      analyses were performed: First, the difference between the same intervals of the
      12 h light or dark period was determined. The macrophage ingestion was
      significantly lower at the beginning and higher at the end of the dark period. We
      have also found a significant increase in blood T-lymphocytes of helper-inducer T
      lymphocyte percentages and of the T helper-inducer: T suppressor-cytotoxic ratio
      during the dark period. Second, the ultradian variation during the 12 h light or
      dark period was determined. The variability was significant both for macrophage
      spreading and ingestion. Multiple significant variations of lymph node, spleen,
      or blood lymphocyte percentages were also observed. All of these data indicate
      that daily alteration of the lighting regimen significantly influences mouse
      peritoneal macrophage functions and various lymphocyte subsets.

PMID- 1394605
TI  - Daily rhythms of metabolic rate and body temperature of two murids from extremely
      different habitats.
AB  - Daily circadian rhythms of body temperature (Tb) and oxygen consumption (VO2)
      were measured in two murid species, which occupy extremely different habitats in
      Israel. The golden spiny mouse (Acomys russatus) is a diurnal murid distributed
      in arid and hot parts of the great Syrio-African Rift Valley, while the broad
      toothed field mouse (Apodemus mystacinus) is a nocturnal species that inhabits
      the Mediterranean woodlands. In both species, the daily rhythms of Tb and VO2 are
      entrained by the photoperiod. Under laboratory experimental conditions (ambient
      temperature Ta = 33 degrees C and photoperiod regime of 12L:12D), Acomys russatus
      exhibits a tendency towards a nocturnal activity pattern, compared to the diurnal
      activity displayed by this species under natural conditions. Under the same
      photoperiod regime and at Ta = 28 degrees C, Apodemus mystacinus displays
      nocturnal activity, as observed under natural conditions. The maximal values of
      Tb were recorded in Acomys russatus at midnight (23:50 h), while the maximal
      values of VO2 were recorded at the beginning of the dark period (18:20 h). In
      Apodemus mystacinus, the maximal values of Tb and VO2 were recorded at 23:40 and
      20:00 h, respectively. The ecophysiological significance of these results is
      discussed further.

PMID- 1394606
TI  - The in vitro effect of metyrapone on steroid synthesis in mice adrenals at
      different circadian stages.
AB  - The circadian rhythm of the in vitro biosynthesis of cortisol and cortisone in
      mice adrenals has been documented in the absence and presence of 0.1 mumol
      metyrapone, an inhibitor of steroid 11 beta-monooxygenase. After 3 weeks of
      synchronization with 12 h light:12 h darkness, adrenalectomy was performed at
      eight circadian stages: 0, 4, 9, 10, 13, 16, 21, and 22 h after light onset
      (HALO). Because it has been shown that mice adrenals could convert exogenous 11
      deoxycortisol, the synthesis of 11-oxysteroids (cortisol+cortisone) in adrenal
      homogenates was studied from tritiated precursor. The pattern of steroid
      synthesis showed a maximum around the end (10 HALO) and a minimum at the
      beginning of the resting period (0 HALO); the variation was approximately 10%. A
      similar pattern was observed in the presence of a approximately 50% inhibiting
      dose of metyrapone. On the other hand, the percent inhibition of 11-oxysteroids
      synthesis was greater at the beginning of the resting period (0 HALO) and minimum
      around the end of the activity span (21 HALO), with an overall variation of 20%.
      However, the variations were statistically insignificant (unpaired t test).

PMID- 1394607
TI  - Vasopressin antagonist disrupts the circadian rhythm of water intake on
      suprachiasmatic injection.
AB  - The present study makes an attempt to find out the action of arginine vasopressin
      (AVP) and its antagonist d-(CH2)5 Tyr (Me) AVP applied at the suprachiasmatic
      nuclei (SCN) on the circadian rhythm of water intake. Chronic implantation of a
      22 G stainless steel cannula for injection was performed using a stereotaxic
      technique under Nembutal anesthesia. AVP and its antagonist were injected into
      the SCN of free-moving rats at the beginning of light and dark phases of the
      light-dark (LD) cycle. Injections of AVP during either phase did not disrupt the
      circadian pattern of water intake while the injections of the antagonist
      disrupted it. The findings are suggestive of the involvement of AVP as a mediator
      of the circadian rhythm of water intake at the level of the neural pacemaker,
      SCN.

PMID- 1394608
TI  - The variability in circadian phase and amplitude estimates derived from
      sequential constant routines.
AB  - Both the constant routine (CR) and the dim light melatonin onset have been
      suggested as reliable methods to determine circadian phase from a single
      circadian cycle. However, both techniques lack published studies quantifying the
      intercycle variability in their phase resolution. To address this question eight
      healthy male subjects participated in two CRs, 7 days apart. Circadian phase was
      determined using 3-min samples of core body temperature and two hourly urinary
      sulphatoxy melatonin excretion rates. Phase and amplitude were estimated using
      simple (24 h) and complex (24 + 12 h) cosinor models of temperature data and the
      onset, offset, and a distance-weighted-least-squares (DWLS) fitted acrophase for
      the melatonin metabolite. The variability in phase estimates was measured using
      the mean absolute difference between successive CRs. Using the simple 24 h model
      of temperature data, the mean absolute phase difference was 51 min (SD = 35 min).
      Using the complex model, the mean absolute phase difference was 62 min (SD = 35
      min). Using the DWLS fitted acrophase for the melatonin metabolite, the mean
      absolute phase difference between CR1 and CR2 was 40 min (SD = 26 min). The
      results indicate that for CRs a week apart, the mean absolute difference in an
      individual's phase estimate can vary by 40-60 min depending on the choice of
      dependent measure and analytic technique. In contrast to the intraindividual
      variability, the group results showed considerably less variability. The mean
      algebraic difference between CRs, using temperature- or melatonin-derived
      estimates, was less than 5 min, and well within the range of normal measurement
      error.

PMID- 1394609
TI  - Rhythmic and nonrhythmic modes of anterior pituitary gland secretion.
AB  - Because of confounding effects of subject-specific and hormone-specific metabolic
      clearance, the nature of anterior pituitary secretory events in vivo is difficult
      to ascertain. We review an approach to this problem, in which deconvolution
      analysis is used to dissect the underlying secretory behavior of an endocrine
      gland quantitatively from available serial plasma hormone concentration
      measurements assuming one- or two-compartment elimination kinetics. This
      analytical tool allows one to ask the following physiological questions: (a) does
      the anterior pituitary gland secrete exclusively in randomly dispersed bursts,
      and/or does a tonic (constitutive) mode of interburst hormone secretion exist?
      and (b) what secretory mechanisms generate the circadian or nyctohemeral rhythms
      in blood concentrations of pituitary hormones?(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394611
TI  - Rhythms in bone marrow cell proliferation: how to apply to the chronotherapy of
      cancer?

PMID- 1394610
TI  - Melatonin shifts human circadian rhythms according to a phase-response curve.
AB  - A physiological dose of orally administered melatonin shifts circadian rhythms in
      humans according to a phase-response curve (PRC) that is nearly opposite in phase
      with the PRCs for light exposure: melatonin delays circadian rhythms when
      administered in the morning and advances them when administered in the afternoon
      or early evening. The human melatonin PRC provides critical information for using
      melatonin to treat circadian phase sleep and mood disorders, as well as
      maladaptation to shift work and transmeridional air travel. The human melatonin
      PRC also provides the strongest evidence to date for a function of endogenous
      melatonin and its suppression by light in augmenting entrainment of circadian
      rhythms by the light-dark cycle.

PMID- 1394612
TI  - Phase relationship between human tumor and bone marrow replication.

PMID- 1394613
TI  - The cellular and molecular basis for divergent allergic responses to chemicals.
AB  - Chemicals vary with respect to the nature of allergic reactions which they will
      elicit preferentially. A wide variety of environmental and industrial chemicals
      are known to cause allergic contact dermatitis (contact sensitivity). Some of
      these are able also to induce respiratory allergy. This article reviews the
      characteristics of immune responses to different classes of chemical allergens
      and the role which functional subpopulations of T helper (TH) cells and their
      soluble cytokine products play in the induction of allergic sensitization. In
      addition, new opportunities to identify and classify chemical allergens based
      upon characterization of divergent allergic responses is discussed.

PMID- 1394614
TI  - 32P-postlabeling of acrolein-deoxyguanosine adducts in DNA after nuclease P1
      digestion.
AB  - In order to study the relationship between the level of acrolein-DNA adducts and
      their biological effects, sensitive methods are needed to quantitate DNA adducts.
      32P-postlabeling is one such method that has been widely used and we have adapted
      the technique to detect acrolein-deoxyguanosine adducts. Adducts formed by the
      reaction of acrolein and deoxyguanosine-3'-monophosphate were isolated by HPLC.
      Based on their UV spectra and cochromatography with standards after
      dephosphorylation with acid phosphatase, these adducts were identified as the
      nucleotide equivalents of cyclic 1,N2-propanodeoxyguanosine adducts formed by
      acrolein that have been described by Chung et al. [15]. As nucleotides, the
      adducts were good substrates for polynucleotide kinase-mediated transfer of
      phosphate from ATP and were able to be detected by 32P-postlabeling. These
      adducts were resistant to the activity of nuclease P1 and dinucleoside
      monophosphates in the form d(G*pN) where G* is the acrolein-guanine adduct also
      resisted digestion by nuclease P1. Digestion of DNA by nuclease P1 and acid
      phosphatase resulted in the conversion of normal nucleotides to nucleosides and
      selective enrichment of the adducts as dinucleoside monophosphates. Using
      nuclease P1/acid phosphatase digestion, followed by 32P-postlabeling and TLC
      separation, levels of the two adducts in acrolein-treated DNA were found to be
      about 6185 and 19,222 nmol/mol.

PMID- 1394616
TI  - Characterisation and quantitation of a selenol intermediate in the reaction of
      ebselen with thiols.
AB  - The reaction of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) with thiols was
      investigated with particular attention to the formation of an ebselen selenol
      intermediate. The selenol intermediate could be trapped in a mixture of ebselen
      and thiols with 1-chloro-2,4-dinitrobenzene and the resulting product displayed
      unique spectral characteristics. The reaction of authentic, synthesised ebselen
      selenol with 1-chloro-2,4-dinitrobenzene (CDNB) was shown to give rise to the
      same compound (2,4-dinitrophenyl (N-phenyl-2-carboxamido phenyl) selenide as
      characterized by light spectroscopy, NMR, IR and elemental analysis. The
      determination of the absorbtion coefficient at 400 nm (E = 7.5 mM-1 cm-1) and the
      initial rate constant of the reaction (1.4 +/- 0.3 mM-1 min-1) allows for the
      convenient quantification of ebselen selenol concentrations by initial rate
      measurements after addition of CDNB. The choice of 400 nm to monitor the reaction
      excludes the interference of other intermediates in the reaction of ebselen with
      thiols as well as the reaction of the thiols with CDNB. When the assay is applied
      to typical incubation conditions used for investigating the glutathione
      peroxidase-like activity of ebselen it was shown that as much as 10-20% of
      ebselen is in the selenol form. If a stronger reductant (dithiothreitol) is used
      60% is in the selenol form. These data could also be confirmed by the direct
      determination of ebselen selenol by UV spectroscopy, due to its peak absorption
      at 370 nm (E = 2 mM-1 cm-1). In conclusion, this investigation demonstrates, for
      the first time, the identity and quantity of ebselen selenol in the reaction of
      ebselen with thiols and also describes a convenient assay for its quantification.
      These observations allow further possibilities for investigation of the molecular
      species responsible for the antioxidant and peroxidase activities of ebselen.

PMID- 1394615
TI  - Effect of fluorine substitution on benzo[j]fluoranthene genotoxicity.
AB  - The metabolism and mutagenic activity of 4-fluorobenzo[j]fluoranthene (4F-B[j]F)
      and 10-fluorobenzo[j]fluoranthene (10F-B[j]F) were evaluated and compared with
      benzo[j]fluoranthene (B[j]F) using an identical rat liver homogenate preparation.
      Previous studies have shown that the major genotoxic metabolites of B[j]F are the
      4,5- and 9,10-dihydrodiol. The 9,10-dihydrodiol was the principal metabolite
      formed in the case of 4F-B[j]F, while the 4,5-dihydrodiol was the principal
      metabolite formed in the metabolism of 10F-B[j]F. Studies on the relative
      genotoxicity of these fluorinated derivatives were performed to indirectly
      determine the possible contribution of the 4,5- and 9,10-dihydrodiol in the
      activation of B[j]F to a genotoxic agent. In the presence of microsomal
      activation, both of these fluorinated derivatives of B[j]F were more mutagenic in
      S. typhimurium TA97a, TA98 and TA100 than B[j]F. However, differences in
      mutagenic potency were observed between 4F- and 10F-B[j]F. 10F-B[j]F had similar
      mutagenic potency to 4F-B[j]F in TA97a and TA98 at doses associated with the
      linear portion of the dose response curve. However, a slightly higher mutagenic
      response was observed with 10F-B[j]F in TA98 at doses above 5 nmol. In contrast,
      4F-B[j]F was more active than 10F-B[j]F as a mutagen in TA100. The tumor
      initiating activity of these analogs on mouse skin was assessed at doses of 2.0,
      1.0 and 0.3 mumol. Skin irritation was observed with the fluorinated B[j]F
      derivatives at doses above 0.3 mumol. At a dose of 0.3 mumol, 4F-B[j]F exhibited
      tumorigenic activity which was similar to B[j]F. In contrast, 10F-B[j]F was less
      active than B[j]F at all three doses assayed. Both fluorinated derivatives of
      B[j]F formed higher levels of DNA adducts in vivo in mouse skin than B[j]F. A
      modified 32P-postlabeling method was required to detect fast migrating B[j]F:DNA
      adducts that went undetected in previous studies. The level of DNA adducts formed
      from 4F-B[j]F was considerably greater than the levels observed with 10F-B[j]F.
      This is consistent with the greater mutagenic activity in S. typhimurium TA100
      and tumor-initiating activity exhibited by 4F-B[j]F. These studies suggest that
      fluorine substitution may significantly alter the intrinsic genotoxicity of the
      4,5- and 9,10-dihydrodiol of B[j]F. These data also imply that B[j]F may be
      primarily activated via the formation of the 9,10-dihydrodiol metabolite. This
      pathway of activation is inconsistent with our previous studies which indicate
      that the 4,5-dihydrodiol is the most important pathway of activation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1394617
TI  - Determination of the relative contributions of the diselenide and selenol forms
      of ebselen in the mechanism of its glutathione peroxidase-like activity.
AB  - The molecular basis of the glutathione peroxidase activity of ebselen (2-phenyl
      1,2-benzisoselenazol-3(2H)-one) was investigated by the use of synthesised,
      authentic intermediates identical to those formed by the reaction of ebselen with
      glutathione. The second order rate constants for the reaction of ebselen (0.29 mM
      1 min-1), ebselen-glutathione selenosulfide (less than or equal to 0.01 mM-1 min
      1), ebselen selenol (2.8 mM-1 min-1) and ebselen diselenide (0.32 mM-1 min-1)
      with hydrogen peroxide reveal that the selenol is particularly active in this
      respect. The determination of the relative amounts of ebselen selenol and
      diselenide under typical peroxidase assay conditions implies that the selenol is
      the predominant molecular species responsible for the glutathione--(70%)--and
      dithiothreitol--(96%)--dependent peroxidase activity of ebselen.

PMID- 1394618
TI  - The effect of six sesquiterpenoid unsaturated dialdehydes on cell membrane
      permeability in human neuroblastoma SH-SY5Y cells.
AB  - The effect of six sesquiterpenes containing an unsaturated dialdehyde
      functionality, on cell membrane permeability in the human neuroblastoma cell line
      SH-SY5Y has been studied. The kinetics of the membrane leakage after addition of
      the sesquiterpenes were determined by measuring the efflux of radioactivity from
      cells preloaded with tritiated 2-deoxyglucose. The concentrations that gave 5%
      and 20% efflux of radioactivity as compared with control cells (EC5 and EC20)
      were determined for each compound. In spite of the structural similarities
      between the compounds, the effects on cell membrane permeability varied
      considerably. EC20 for polygodial, which is the most active compound, is 2.5
      microM after 20-min incubation, but no leakage could be determined for merulidial
      even at concentrations as high as 4 mM. Rather, this compound seems to stabilize
      or fix the cell membrane and a lower efflux of radioactivity was observed as
      compared to the control cells. A quantitative structure-activity relationship
      analysis for the five active compounds showed a good correlation between the
      membrane leakage activity and certain chemical characteristics. Structural
      features strongly correlated with high activity were found to be: The geometry
      and the atomic charges of the unsaturated dialdehyde functionality, the dipole
      moment, the energy difference between the lowest unoccupied molecular orbital and
      the highest occupied molecular orbital and the lipophilicity.

PMID- 1394619
TI  - The relative importance of glutathione and metallothionein on protection of
      hepatotoxicity of menadione in rats.
AB  - The effects of induction of metallothionein (MT) on the toxicity of menadione
      were investigated in rat liver slices. The protective role of hepatic glutathione
      (GSH) was also studied and compared to that of MT. A 3-h incubation of rat liver
      slices with menadione (100-300 microM) containing medium (37 degrees C, pH 7.4,
      95%O2:5%CO2) resulted in cellular toxicity, as shown by changes in cytosolic K,
      Ca and GSH concentrations and lactate dehydrogenase (LDH) leakage. A dose
      dependent decrease in cytosolic K and GSH was observed concomitant with an
      increase in cytosolic Ca and LDH leakage after incubation with menadione.
      Pretreatment of rats with zinc sulphate (ZnSO4) (30 mg/kg body wt.) increased MT
      levels in liver slices and suppressed the toxicity of menadione. Intracellular
      GSH concentrations in liver slices were either depleted or increased by injection
      of rats with buthionine sulfoximine (BSO), (4 mmol/kg body wt.) and N-acetyl-L
      cysteine (NAC) (1.6 g/kg body wt.), respectively. Intracellular GSH was found to
      be crucial in protection against menadione toxicity. Menadione toxicity was
      increased when the rats were injected with sodium phenobarbital (PB) (4 x 80
      mg/kg body wt.). Pretreatment with Zn provided partial protection against
      menadione toxicity in liver slices from both BSO- and PB-injected rats. These
      findings suggest that induction of MT synthesis does protect against quinone
      induced toxicity, but the role may be secondary to that of GSH. The mechanisms by
      which MT protect against menadione toxicity are still unclear but may involve
      protection of both redox cycling and sulphydryl arylation.

PMID- 1394620
TI  - Glutathione disulfide reduction in tumor mitochondria after t-butyl hydroperoxide
      treatment.
AB  - Treatment of isolated mitochondria from rat hepatoma tumor cells (AS-30D) with
      the oxidant, t-butyl hydroperoxide (tBuOOH, 1 or 5 mumol/ml) resulted in the
      oxidation of glutathione (GSH to GSSG) and the formation of protein-glutathione
      mixed disulfides (ProSSG). The GSSG was retained inside of the hepatoma
      mitochondria. In the presence of ADP+succinate (5 or 10 mM), or ketoglutarate (10
      mM) or malate (5 mM), the GSSG was reduced to GSH, but the amount of ProSSG
      stayed constant. With saline or ADP+glutamate (10 mM)/malate (0.1 mm) no
      reduction of GSSG to GSH occurred. The presence of antimycin (5 micrograms/ml)
      with ADP+succinate inhibited reduction. At a concentration of 1,3-bis(2
      chloroethyl)-1-nitrosourea (BCNU, 0.5 mM) which inhibited a major portion of the
      glutathione reductase activity, the reduction of GSSG to replenish GSH was also
      inhibited. NADPH may play a critical role as well, for the addition of 2.4 mM
      NADPH to permeabilized hepatoma mitochondria fostered the reduction of GSSG after
      tBuOOH treatment. Therefore, hepatoma mitochondria possess a glutathione
      reductase-dependent system to reduce GSSG to GSH. The reaction only occurs with
      actively respiring mitochondria.

PMID- 1394621
TI  - The effect of 2,2'-dichlorodiethyl sulfide on DNA synthesis of a murine
      stratified keratinocyte culture system.
AB  - A primary stratified keratinocyte culture resembling the epidermis in situ was
      used as a model for studying the effects of exposure to 2,2'-dichlorodiethyl
      sulfide, or sulfur mustard (SM), on DNA synthesis. A method that distinguishes
      between semi-conservative (s.c.) DNA synthesis and repair synthesis was used to
      determine if the former was inhibited following treatment with SM. In this method
      the density of the newly synthesized DNA was increased by incorporation of 5
      bromo-2-deoxyuridine. Density gradient centrifugation was then used to isolate
      the heavy DNA for quantification. It was demonstrated that topically applied SM
      in the dose range of 1-10 nmole/cm2 inhibited s.c. DNA synthesis (replication) in
      a dose and time related manner. Inhibition of DNA replication by SM would result
      in inhibition of cell division which must be preceded by s.c. DNA synthesis. This
      failure to replace damaged germinative cells may lead to the destruction of the
      basal layer which is observed in vivo and in our epidermal culture following
      exposure to SM. This may also be related to development of vesication observed in
      exposed intact human skin.

PMID- 1394622
TI  - Polycyclic aromatic hydrocarbon (PAH) ortho-quinone conjugate chemistry: kinetics
      of thiol addition to PAH ortho-quinones and structures of thioether adducts of
      naphthalene-1,2-dione.
AB  - Polycyclic aromatic hydrocarbon (PAH) o-quinones are products of an NADP+
      dependent oxidation of non-K-region trans-dihydrodiols catalyzed by dihydrodiol
      dehydrogenase (EC 1.3.1.20). Since these PAH o-quinones could be detoxified by
      non-enzymatic or enzymatic conjugation with cellular thiols, their reactivity
      with 2-mercaptoethanol, cysteine and glutathione (GSH) was examined by ion-pair
      reverse phase high pressure liquid chromatography (RP-HPLC). Second-order rate
      constants for the addition of these thiols to naphthalene-1,2-dione (NPQ) in
      water ranging from 4.9 x 10(3) - 1.1 x 10(4) min-1 M-1 and the reactions were
      complete within 10 min. When these reactions were conducted at near physiological
      pH (50 mM potassium phosphate buffer pH 7.0), the rate constants increased by 2
      orders of magnitude. When benzo[a]pyrene-7,8-dione (BPQ) was substituted in these
      reactions the second-order rate constants decreased by 2-3 orders of magnitude
      and the reactions took several hours to reach completion. The decrease in
      reactivity can be explained by the presence of the bay region in BPQ. Methylation
      influenced the reactivity of PAH o-quinones with GSH and the following order of
      reactivity was observed: 7,12-dimethyl-benz[a]anthracene-3,4-dione (7,12-DMBAQ)
      >> 12-methyl-BAQ, 7-methyl-BAQ and BAQ >> BPQ. Of these quinones 7,12-dimethyl
      BAQ was almost equi-reactive with NPQ. This suggests that methyl substitution in
      the bay and peri regions enhances reactivity with GSH. Using NPQ as a model for
      other PAH o-quinones, N-acetyl-L-cysteine, L-cysteine and GSH conjugates of NPQ
      were synthesized and characterized by [1H]- and [13C]NMR. Evidence for Michael
      type 1,4-addition products was obtained in which the resultant adduct could exist
      as either a catechol or o-quinone. By contrast, L-cysteine was able to form
      adducts via S- or N-attack and N-attack gave a purple p-iminoquinone. There was
      no evidence for the formation of bis-N-acetyl-L-cysteinyl-, bis-glutathionyl
      adducts or phenolic coupled products. The toxicity of thiol conjugates of NPQ
      remains to be explored.

PMID- 1394623
TI  - The reaction of melphalan with deoxyguanosine and deoxyguanylic acid.
AB  - The reaction of melphalan (phenylalanine mustard, I) with 2'-deoxyguanosine,
      followed by removal of the sugar in acid, yielded two products. The major product
      was identified as 4-(N-(2-guanin-7-ylethyl)-N-(2-hydroxyethyl)amino)phenyl-
      alanine (II) by ultra-violet absorption, mass and NMR spectroscopy. The minor
      product has already been identified as the corresponding bis-guaninyl adduct III
      (Tilby et al., Chem.-Biol. Interact., 73 (1990) 183-194). The reaction of
      melphalan with 5'-deoxyguanylic acid yielded the deoxyribonucleotide of II and
      products resulting from reaction with the phosphate group. The initial products,
      which were formed with a half-life of approximately 40 min at 37 degrees, still
      had a reactive chloroethyl group; this was displaced more slowly, by reaction
      with water or with another molecule of dGMP. The products of reaction of
      melphalan with DNA were released by treatment with acid (0.1 M HCl, 70 degrees,
      30 min) and separated from each other on a cation exchange column. They were
      identified as II, III and an adenine adduct, in a ratio of approximately 3:1:2.

PMID- 1394624
TI  - In vitro activation of heat shock transcription factor by 4-hydroxynonenal.
AB  - In the activation of eukaryotic heat shock genes, the acquisition of a binding
      ability to specific DNA sequence by a transcriptional activator, heat shock
      factor (HSF), is believed to be a crucial step. The induction of this new DNA
      binding activity of HSF is also obtained in a cell-free system (in vitro
      activation) by hyperthermia or at physiological temperature by calcium ions, low
      pH, urea, or non-ionic detergent. We report here the in vitro activation of HSF
      by treating at 0 degrees C a HeLa cell-free system with the aldehyde 4
      hydroxynonenal (HNE), a highly cytotoxic product of lipid peroxidation. The in
      vitro activation of HSF by HNE occurred only if some components of the cell-free
      system were not sedimented at 100,000 x g. The reason for this is unclear but the
      release of active HSF from nuclei of unshocked cells and the involvement of Ca2+
      contained in the mitochondria and ER have been excluded. Although HNE is known to
      be a sulfhydryl blocking agent, the results obtained with N-ethylmaleimide
      suggest that different mechanisms might be involved in the in vitro activation of
      HSF by HNE.

PMID- 1394625
TI  - Synthetic studies of carbapenem and penem antibiotics. II. Synthesis of 3-acetyl
      2-azetidinones by (2 + 2) cycloaddition of diketene and Schiff bases.
AB  - It was found that (2 + 2) cycloaddition reaction of diketene with Schiff bases
      was effectively promoted by imidazole as a catalyst to afford 3-acetyl-2
      azetidinone derivatives 4. As an application of this new method, a practical
      asymmetric synthesis of 4 and its conversion into (3S,4S)-4-carboxy-1-(di-p
      anisylmethyl)-3-[(R)-1-hydroxyethyl]-2- azetidinone, which is a key intermediate
      for the synthesis of carbapenem and penem antibiotics, were accomplished.

PMID- 1394626
TI  - Synthetic studies of carbapenem and penem antibiotics. III. A synthesis of a key
      intermediate for 1 beta-methylcarbapenem.
AB  - We synthesized useful intermediates 5 and 6 for 1 beta- and 1 alpha
      methylcarbapenems from 4-carboxy-3-[(R)-1-hydroxyethyl]-2-azetidinone 4 as a
      starting material by using stereoselective hydrogenation and hydroboration,
      respectively. A practical synthetic route from 4 to the (3S,4S)-4-[(R)-1
      carboxyethyl]-3-[(R)-1-hydroxyethyl]-2-azetidinone derivative 1, a useful
      intermediate for the synthesis of 1 beta-methylcarbapenem antibiotics, was
      established.

PMID- 1394627
TI  - Isolation and structures of antibacterial binaphtho-alpha-pyrones, talaroderxines
      A and B, from Talaromyces derxii.
AB  - New compounds designated talaroderxines A (1) and B (2) were isolated from a new
      heterothallic ascomycetous fungus, Talaromyces derxii, cultivated on rice. The
      structures of 1a and 1b were elucidated by means of spectroscopic examination and
      chemical reactions. Talaroderxines A (1a) and B (1b) are atropisomers of a 6,6'
      binaphtho-alpha-pyrone derivative, and have strong antibacterial activity against
      Bacillus subtilis.

PMID- 1394628
TI  - Preparation of three positional isomers of diglucosyl-cyclomaltohexaose.
AB  - Three positional isomers of diglucosyl-cyclomaltohexaose (diglucosyl-cG6) were
      chemically synthesized via 6(1),6(2)-, 6(1),6(3)-, and 6(1),6(4)-di-O-(TERT
      butyldimethylsilyl)-cG6S (1, 2, and 3) prepared regiospecifically. Glucosylation
      of bis(2,3-di-O-acetyl)tetrakis(2,3,6-tri-O-acetyl)-CG6S obtained from the three
      regioisomeric compounds 1, 2, and 3 with 2,3,4,6-tetra-O-benzyl-1-O
      trichloroacetimidoyl-alpha-D-glucopyran ose, followed by debenzylation and then
      deacetylation, afforded 6(1),6(2)-, 6(1),6(3)-, and 6(1),6(4)-di-O-(alpha-D
      glucopyranosyl)-cG6S (10, 11, and 12) together with configurational isomers. The
      desired compounds 10, 11, and 12 containing two (1----6)-alpha-linkages were
      isolated from the mixtures of their configurational isomers by high performance
      liquid chromatography. The three diglucosyl-cG6S synthesized chemically were used
      as authentic samples to identify the components in a mixture of diglucosyl-cG6S
      produced by an enzymatic process.

PMID- 1394629
TI  - Syntheses of a glycerophospholipid, C16-platelet activating factor and a
      palmitoyl analogue of M-5, an anti-inflammatory glyceroglycolipid.
AB  - From a chiral C4-epoxide (-)-3, which is one of the synthons in our synthetic
      strategy for complex lipids, a glycerophospholipid C16-platelet activating factor
      (C16-PAF, 1) and a palmitoyl analogue (2) of an anti-inflammatory
      glyceroglycolipid M-5, which was previously isolated from the Okinawan marine
      sponge Phyllospongia foliascens, have been synthesized.

PMID- 1394630
TI  - Synthesis and antibacterial activity of some imidazo[1,2-a]pyrimidine
      derivatives.
AB  - A series of 75 imidazo[1,2-a]pyrimidine derivatives were synthesized. The "in
      vitro" antibacterial activity of these compounds and their corresponding alpha
      bromoketones against a variety of gram (+), gram (-) bacteria and Mycobacterium
      species is reported. Some of the prepared derivatives exhibited potent
      antimicrobial activity.

PMID- 1394631
TI  - Central cholinergic agents. III. Synthesis of 2-alkoxy-2,8- diazaspiro[4.5]decane
      1,3-diones as muscarinic agonists.
AB  - A series of 2-alkoxy-2,8-diazaspiro[4.5]decane-1,3-diones and related compounds
      were synthesized and tested for muscarinic receptor binding affinity using
      [3H]pirenzepine and [3H]oxotremorine M as ligands. They were also evaluated for
      agonistic activities in the guinea pig ileum assay. 2-Methoxy- 2,8
      diazaspiro[4.5]decane-1,3-dione (1i) was found to be a relatively M1 selective
      agonist. It reversed CO2-induced impairment of passive avoidance response with
      long duration of action, but also displayed peripheral effects at low doses. To
      minimize these side effects, we proposed the idea of conjugation of 1i with a
      muscarinic antagonist. The carbamate linked conjugate (1u) of 1i with
      methylatropine was therefore examined.

PMID- 1394632
TI  - Synthesis of N-substituted C-normorphinans and their pharmacological properties.
AB  - Several N-substituted C-normorphinans (VIII and IX) were synthesized and tested
      for their analgetic and narcotic antagonist activities and physical dependence
      capacity. Treatment of N-formyl- octahydro-2-pyrindine (IIIc) with polyphosphoric
      acid readily gave N-formyl-C-normorphinan (IV). The N-nor bases (V and VII)
      obtained from IV were converted to VIII and IX. The N-methyl derivative (I),
      which was previously reported to be inactive by Haffner's method, exhibited
      potent analgetic activity by the hot plate method and the AcOH-induced writhing
      test. Compounds VIII and IX showed pharmacological properties similar to those of
      N-substituted morphinans and exhibited agonist (analgetic) and/or narcotic
      antagonist activities. The C-nor analogue (IXa) of cyclorphan (IIc) exhibited
      potent analgetic and antagonist activities with no physical dependence capacity
      in the single-dose suppression tests both in rats and monkeys.

PMID- 1394634
TI  - 7-Oxodihydrokarounidiol [7-oxo-D:C-friedo-olean-8-ene-3 alpha,29-diol], a novel
      triterpene from Trichosanthes kirilowii.
AB  - The structure of 7-oxodihydrokarounidiol [7-oxo-D:C-friedo-olean-8-ene-3 alpha,29
      diol], isolates from the seeds of Trichosanthes kirilowii (Cucurbitaceae), was
      determined by chemical correlation with karounidiol [D:C-friedo-oleana-7,9(11)
      diene-3 alpha,29-diol] from the same source. Two other natural products, viz.
      bryonolic acid (3 beta-hydroxy-D:C-friedo-olean-8-en-29-oic acid) and bryononic
      acid (3-oxo-D:C-friedo-olean-8-en-29-oic acid), were also correlated with
      karounidiol.

PMID- 1394633
TI  - Platelet activating factor (PAF) antagonists contained in medicinal plants:
      lignans and sesquiterpenes.
AB  - Hot aqueous extracts of medicinal plants were tested for their inhibitory effect
      on the binding of platelet activating factor (PAF) to rabbit platelets. The
      extracts of Forsythia suspensa VAHL. (Oleaceae), Arctium lappa L. (Compositae)
      and Centipeda minima (L.) A. BRAUN et ASCHERS (Compositae) showed significant
      activities. Since the main constituents of F. suspensa and A. lappa are lignans,
      30 lignans were tested for their inhibitory effects on PAF binding to platelets
      and 9 lignans were found active. Four sesquiterpenes were isolated as active
      compounds from C. minima. In particular 6-O-angeloylplenolin and 6-O
      senecioyplenolin are the most potent and specific PAF antagonists found in this
      study.

PMID- 1394635
TI  - Studies on the conformational aspects of inulin oligomers.
AB  - The conformational studies of inulin oligomers from G-F2 to G-F9, which isolated
      from Platycodon grandiflorum, suggested a plausible conformational change between
      G-F7 and G-F8 from the trends in their chemical shift patterns and molecular
      rotation; the oligomers higher than G-F8 would form some secondary conformations
      more rigid than shorter oligomers. On the other hand, spin-lattice relaxation
      (T1) studies of the protons proposed through-space interactions of 2- and 4-H's
      of glucose moiety in G-F5, presumably with some atom(s) of the terminal fructose
      moiety. This would reflect that the inulin molecule adopts a 5/1 helix.

PMID- 1394636
TI  - Inhibitory effects of glycyrrhetic acid and its related compounds on 3 alpha
      hydroxysteroid dehydrogenase of rat liver cytosol.
AB  - Glycyrrhetic acid (GA), aglycone of glycyrrhizin (GL), inhibited potently (I50 =
      7 x 10(-6) M) and non-competitively the activity of NAD(P)+-linked 3 alpha
      hydroxysteroid dehydrogenase of rat liver cytosol. The inhibition was slightly
      weaker than that of indomethacin, a potent anti-inflammatory agent, but stronger
      than that of dexamethasone, another anti-inflammatory agent. GL, GA
      monoglucuronide, and 3-epi-glycyrrhetic acid also inhibited this enzyme activity,
      but did so less effectively (I50 = 5-8 x 10(-5) M). Carbenoxolone (GA 3
      hemisuccinate) and 3-keto-glycyrrhetic acid showed potent inhibitory effects
      similar to GA, and 18 alpha-GA showed the most powerful inhibition of the
      activity.

PMID- 1394637
TI  - Biochemical studies on oral toxicity of ricin. V. The role of lectin activity in
      the intestinal absorption of ricin.
AB  - In order to investigate a possible role of lectin activity of ricin in its
      absorption from the small intestine, we prepared two ricin derivatives. BMH
      ricin, prepared by crosslinking A and B chains of ricin with 1,6
      bismaleimidohexane, was nearly non-toxic but the lectin activity was unaltered.
      And, NBS-ricin, prepared by the oxidation of tryptophanyl residues of ricin with
      N-bromosuccinimide, was not only non-toxic but also non-lectinic. After the oral
      administration of ricin derivatives to rats, their interaction with the digestive
      tract and absorption into the circulatory systems have been compared with those
      of ricin, immunochemically and histologically. It was shown by immunostaining
      that ricin and BMH-ricin could bind to the intestinal mucosa, whereas NBS-ricin
      could not. No appreciable damage in the small intestine from rats treated with
      either BMH-ricin or NBS-ricin has been observed, in contrast to ricin treatment
      where severe impairment of the small intestinal tissues resulted after 5 h.
      Immunoreactive ricin in the liver has been determined with the ricin enzyme
      immunoassay (EIA). When compared at 48 h after oral administration, NBS-ricin was
      not detected, whereas BMH-ricin was found to be 38 micrograms/liver and ricin 100
      micrograms/liver. From these results, it was inferred that the lectin activity of
      ricin plays an important role in the absorption of ricin from the small intestine
      and that the absorption of ricin protein was enhanced by its high toxicity.

PMID- 1394639
TI  - Characterization of cationic acid phosphatase isozyme from rat liver
      mitochondria.
AB  - Acid phosphatase isozyme was highly purified from rat liver mitochondrial
      fraction. The enzyme showed an isoelectric point value of above 9.5 on
      isoelectric focusing, and the apparent molecular weight was estimated to be 32000
      by Sephadex G-100 gel filtration or 16000 by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. The enzyme catalyzed the hydrolysis of
      adenosine 5'-triphosphate, adenosine 5'-diphosphate, thiamine pyrophosphate,
      inorganic pyrophosphate, and phosphoprotein such as casein and phosvitin, but not
      of several phosphomonoesters, except for p-nitrophenyl phosphate and o
      phosphotyrosine. The enzyme was not inhibited by L-(+)-tartrate, and was
      significantly activated by Fe2+ and reducing agents such as ascorbic acid, L
      cysteine,and dithiothreitol. The enzyme was found to be distributed in various
      rat tissues including liver, spleen, kidney, small intestine, lung, stomach,
      brain and heart, but not in skeletal muscle.

PMID- 1394638
TI  - Conformation-dependent change in antitumor activity of linear and branched (1---
      3)-beta-D-glucans on the basis of conformational elucidation by carbon-13 nuclear
      magnetic resonance spectroscopy.
AB  - The antitumor activity of (1----3)-beta-D-glucans was tested in order to clarify
      its conformation-dependent response together with conformational elucidation by
      carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy. It was shown that
      the following three conformations, single chain, single helix and triple helix,
      are readily distinguished by the high-resolution solid-state 13C-NMR method. It
      turned out that preparations of linear (1----3)-beta-D-glucans of a triple
      helical conformation were ineffective in the inhibition of tumor growth. These
      linear (1----3)-beta-D-glucans were converted to an effective form in the
      inhibition of tumor growth when they were lyophilized from dimethyl sulfoxide
      (DMSO) solutions as a result of a conformational change from the triple helical
      to the single chain forms. They were not effective, however, when assayed in DMSO
      solution. In contrast, it was found that a branched (1----3)-beta-D-glucan is
      effective not only in either saline solutions of the triple helical sample or the
      lyophilized sample from DMSO, but also in DMSO solution. The aforementioned
      drastic change in antitumor activity was interpreted in terms of resulting
      conformational changes as analyzed by the 13C-NMR method.

PMID- 1394640
TI  - Purification and characterization of gamma-enolase from various mammals.
AB  - The gamma subunit of enolase (gamma-enolase) was purified from the brain tissues
      of cow, dog, goat, pig, rabbit, and rat. The purification was achieved in only
      three steps: ammonium sulfate-precipitation, DE 53 cellulose ion-exchange
      chromatography, and polyacrylamide gel electrophoresis (PAGE) in a preparative
      mode. The purification procedure was comparatively more simple than previously
      reported methods, and the yield of gamma-enolase was sufficient for subsequent
      structural and immunological analyses. In all mammals, the purified gamma-enolase
      migrated in sodium dodecyl sulfate-PAGE (SDS-PAGE) with a molecular mass of 46
      kilodaltons (kDa), and the immunological cross-reactivity between those gamma
      enolases was very strong. The structural homology of these gamma-enolases was
      examined by peptide mapping using cyanogen bromide cleavage and subsequent two
      dimensional electrophoresis. The resulting peptide patterns were highly similar
      and in cow, dog, and goat, the patterns were almost identical. These results
      indicate that structural homology, that is, the species non-specificity of gamma
      enolase, appears to be very high.

PMID- 1394641
TI  - Fluconazole: a potent inhibitor of cytochrome P-450-dependent drug-metabolism in
      mice and humans in vivo. Comparative study with ketoconazole.
AB  - The inhibitory effect of fluconazole (FCZ), a bis-triazole antimycotic, on mouse
      hepatic microsomal cytochrome P-450-mediated drug-metabolizing enzyme system was
      compared with those of ketoconazole (KCZ) in vivo and in vitro. Additionally, the
      change in the hepatic oxidative drug-metabolizing capacity in humans treated with
      FCZ was followed. The pentobarbital sleeping time in mice given a single dose of
      1-10 mg/kg of FCZ or 30-50 mg/kg of KCZ was prolonged significantly, and the
      potency of FCZ for the prolongation of sleeping time was greater than that of
      KCZ. In contrast, in vitro the affinity and the inhibitory potency of FCZ for
      cytochrome P-450 and aminopyrine N-demethylation were 4- to 6-fold smaller than
      those of KCZ. However, the order of the inhibitory potencies among antimycotics
      for this enzyme systems in vitro was reversed by the addition of albumin into the
      reaction mixture. These results indicate that the difference in the plasma
      protein binding properties between FCZ and KCZ is an important factor which leads
      to a reverse in the order of their inhibitory potencies for this enzyme system in
      vitro and in vivo. The ratio of 6-beta-hydroxycortisol (6 beta-OHF) to cortisol
      (F) in urine, used as an indicator of oxidative drug-metabolizing capacity in
      humans, decreased to 50% of the original level during treatment with 200 mg/d of
      FCZ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394642
TI  - Effect of cyclodextrins on biological membrane. II. Mechanism of enhancement on
      the intestinal absorption of non-absorbable drug by cyclodextrins.
AB  - The effects of two kinds of cyclodextrins (CyDs), alpha- and beta-CyD, on
      biological membranes were investigated by measuring changes in the absorption of
      a non-absorbable drug, sulfanilic acid (SA), from the rat small intestine, using
      in situ and in vitro experiments. After pretreatment with a mucolytic agent, N
      acetyl-L-cysteine (N-Ac), only beta-CyD increased the absorption of SA
      significantly compared to the absorption without pretreatment. The mechanism of
      the enhancing effect of CyDs on the absorption of SA was discussed. Almost no
      morphological change in the small intestine was observed by pretreatment with N
      Ac alone, N-Ac or alpha- or beta-CyD combinations. The liberation of membrane
      components differed among the CyDs, e.g., alpha-CyD selectively released
      phospholipid while beta-CyD released mainly cholesterol from the intestinal
      membrane. It is suggested that the interaction of membrane components with CyDs
      may be at least partly responsible for the enhanced absorption of SA. Moreover it
      was found from in vitro electrophysiological experiment, that the alteration in
      enhanced permeability caused by beta-CyD occurred primarily in the transcellular
      pathways, rather than in the paracellular pathways of the small intestine. These
      results suggest that the enhancement of intestinal absorption by beta-CyD, after
      removal of the mucin layer from the intestinal surface, is due to the interaction
      between the membrane components and CyD. This interaction would induce disorder
      in cell membrane lipid, resulting in the increased permeability of the
      transcellular route.

PMID- 1394643
TI  - Interaction between polyethylene films and bromhexine HCl in solid dosage form.
      IV. Prevention of the sorption by addition of magnesium aluminum silicate.
AB  - The effects of magnesium aluminum silicate (MAS) addition on the sorption of
      bromhexine HCl to polyethylene film in tablets were studied. The addition of MAS
      prevented the sorption of bromhexine HCl to polyethylene film. In order to
      investigate the mechanism, the interaction between bromhexine HCl and MAS was
      studied by the powder X-ray diffraction method. It was observed that bromhexine
      HCl was preferentially adsorbed to the surface of MAS rather than to polyethylene
      film. The adsorption was accelerated at high temperature and reduced pressure
      conditions. The sorption of bromhexine base and bromhexine HCl to packaging
      material were compared using tablet dosage forms. The sorption of bromhexine base
      to polyethylene film was greater than that of bromhexine HCl.

PMID- 1394644
TI  - An assessment of indomethacin-induced mucosal damage in vivo by measuring the
      metabolism of salicylamide in rabbit intestine.
AB  - Indomethacin-induced mucosal damage was assessed in vivo by measuring
      salicylamide (SAM) metabolism in rabbit intestine. Intestinal mucosal damage 48 h
      after oral indomethacin (500 mg/kg) administration was examined using a scanning
      electron microscope. Duodenal, jejunal and ileal mucosal toxicity was compared
      with that in controls. Intestinal first-pass metabolism of SAM was studied using
      in situ intestinal sacs with intact mesenteric venous blood collection. The
      appearance of both SAM and its metabolites in the mesenteric venous blood was
      measured following cannulation of the mesenteric vein of the exposed intestine
      and collecting all venous blood draining from the absorbing region. Following
      oral pretreatment with indomethacin, the appearance of SAM and SAM glucuronide
      (SAMG) in the mesenteric venous blood was significantly increased. The
      concentrations of SAM and SAMG in the blood increased following intraduodenal
      administration of SAM in vivo in rabbits orally pretreated with indomethacin
      compared with controls. However, after intravenous administration of SAM, the
      blood concentration of SAM and SAMG was not increased compared with controls.
      These findings suggest that the differences in intestinal first-pass metabolism
      of SAM may be due to the intestinal mucosal damage induced by oral indomethacin
      pretreatment. The results indicate that the alteration of intestinal first-pass
      metabolism of a marker compound may be utilized to assess intestinal mucosal
      damage in vivo.

PMID- 1394645
TI  - Homeostasis as regulated by activated macrophage. VI. Protective effect of LPSw
      (a lipopolysaccharide from wheat flour) against acute infection by Toxoplasma
      gondii in mice.
AB  - An oral administration of partially purified LPSw, a lipopolysaccharide (LPS)
      from wheat flour, at a concentration of 20 ng/ml in drinking water beginning 1d
      after infection significantly decreased mouse mortality and prevented animal
      weight loss in acute infection with Toxoplasma gondii. Whereas 71% (5/7) of mice
      in a control group that did not receive LPSw died of toxoplasmosis, only 14%
      (1/7) of mice treated with LPSw died (p less than 0.05). The administration of
      LPS purified from Bordetella pertussis also significantly decreased the mortality
      of infected mice. LPS from Escherichia coli and synthetic lipid A (LA-15
      PP(506)), however, did not show a significant decrease in mortality.

PMID- 1394646
TI  - Homeostasis as regulated by activated macrophage. VII. Suppression of serum
      cholesterol level by LPSw (a lipopolysaccharide from wheat flour) in WHHL
      (Watanabe heritable hyperlipidemic) rabbit.
AB  - The effect of LPSw (a lipopolysaccharide from wheat flour) on cholesterol
      catabolism was examined using WHHL (Watanabe heritable hyperlipidemic) rabbit,
      which is an experimental model of familial hyperlipidemia. The serum cholesterol
      level of the animal decreased by the addition of LPSw to drinking water.
      Following cessation of the addition of LPSw to the drinking water, the
      cholesterol level was decreased for 30 to 40d and then gradually elevated. The
      serum level of apolipoprotein B, which is a constituent of apolipoprotein of low
      density lipoprotein (LDL), also decreased in accord with serum cholesterol at a
      nearly coincident rate. Conversely, the level of apolipoprotein A-I, which is a
      constituent of apolipoprotein of high density lipoprotein (HDL), did not change,
      nor did HDL-cholesterol. Furthermore, the atherosclerosis risk factor, expressed
      as the ratio of apolipoprotein B to apolipoprotein A-I, was decreased by LPSw
      administration.

PMID- 1394647
TI  - Homeostasis as regulated by activated macrophage. VIII. LPSw (a
      lipopolysaccharide from wheat flour) can regulate bone resorption of chick
      embryo.
AB  - The effect of LPSw (a lipopolysaccharide from wheat flour) on the bone resorption
      of 18-d chick embryonic calvaria was examined in an organ culture following the
      method of Raisz. Bone was prelabeled in culture medium containing 45Ca and chased
      in a cold medium. On addition of test samples, labeled calcium was released
      indicating the grade of bone resorption. LPSw (10-100 ng/ml) stimulated bone
      resorption, showing an effect comparable to parathyroid hormone (PTH) (1 U/ml).
      PTH at 1 U/ml decreased the total amount of calcium and phosphorus, while LPSw
      did not. LPSw is thus assumed to stimulate bone resorption more actively than
      PTH.

PMID- 1394648
TI  - Homeostasis as regulated by activated macrophage. IX. Enhancement effect of LPSw
      (a lipopolysaccharide from wheat flour) on hen egg-laying and breaking strength
      of eggshell.
AB  - Oral administration of LPSw (a lipopolysaccharide from wheat flour) given at 60
      micrograms/hen/d in drinking water, markedly enhanced eggshell strength. The
      monthly percentage of eggs laid with a shell strength of more than 4 kg to the
      total number of eggs was 32% in the group given LPSw in drinking water while it
      was 12% in the control group given plain water. At the same time, LPSw caused a
      30% enhancement of total monthly number of eggs laid over that of control.

PMID- 1394649
TI  - Pharmacoepidemiological study on adverse reactions of antiepileptic drugs.
AB  - The relationship between the occurrence of side effects (SEs) and drug factors,
      such as antiepileptic drugs (AEDs), daily dose, duration of treatment, drug
      combination pattern, total and free serum concentrations, metabolite per parent
      level ratio as an index of metabolism ability, and co-medicated drugs except AEDs
      were evaluated in 227 outpatients with epilepsy. The possible influences of
      certain physiological and/or the pathophysiological factors were also evaluated.
      SEs with 19 clinical signs were observed in 66.1% of all patients. There was no
      definite dose- or serum concentration-dependent increase in the incidence of SEs.
      Stepwise discriminant function analysis revealed that benzodiazepines (BZN)
      polytherapy with AEDs produced a higher incidence of somnolence and general
      fatigue than did any other AED or drug combination. The effects of various drug
      combination patterns on the incidence of SEs were also evaluated on the basis of
      observed frequencies. The incidence of somnolence was significantly higher in
      patients taking phenytoin (PHT) plus carbamazepine (CBZ) therapy, and in patients
      taking BZN plus either PHT, phenobarbital (PB) or CBZ therapy compared with
      patients taking either PHT, PB or CBZ therapy. Other responsible drug combination
      patterns were PHT plus valproic acid (VPA) therapy for mental function
      impairment, acetazolamide (AZM) polytherapy with PB or PHT for dry mouth, and CBZ
      plus BZN therapy for constipation. In this study, the stratifying points
      (occurrence limits) of SEs were detected in various variables such as the number
      of prescribed drugs, daily dose and serum concentrations. Interestingly, these
      limits are within the commonly accepted "therapeutic range" or "usual daily
      dose," and some of these limits shifted down when another AED was co
      medicated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394650
TI  - Pharmacokinetics of [6]-gingerol after intravenous administration in rats with
      acute renal or hepatic failure.
AB  - The pharmacokinetics of [6]-gingerol were investigated in rats with acute renal
      failure induced by bilateral nephrectomy, or those with acute hepatic failure
      induced by a single oral administration of carbon tetrachloride (CCl4), to
      clarify the contribution of the kidney and liver to the elimination process of
      [6]-gingerol. After bolus intravenous administration, a plasma concentration-time
      curve of [6]-gingerol was illustrated by a two-compartment open model. There was
      no significant difference in either the plasma concentration-time curve or any
      pharmacokinetic parameters between the control and nephrectomized rats. It is
      suggested, therefore, that renal excretion does not contribute at all to the
      disappearance of [6]-gingerol from plasma in rats. In contrast, hepatic
      intoxication with CCl4 elevated the plasma concentration of [6]-gingerol at the
      terminal phase. Its elimination half-life increased significantly, from 8.5 to
      11.0 min, in CCl4-intoxicated rats. The extent of [6]-gingerol bound to serum
      protein was more than 90% and was affected very slightly by the CCl4
      intoxication. These aspects indicate that [6]-gingerol is eliminated partly by
      the liver.

PMID- 1394651
TI  - Relationship between the effects on bacterial activity of selected disinfectants
      and the hydrophobic characters of dibasic acid diesters.
AB  - We prepared test solutions which contained 80% (v/v) ethanol and 0.2% (w/v)
      chlorhexidine (CH) or benzalkonium chloride (BC) with or without a dibasic acid
      diester. After complete evaporation of the ethanol from the solution on filter
      paper, an overnight broth culture (Staphylococcus aureus) was repeatedly
      inoculated onto the filter paper, and viable bacterial counts were measured at 5
      min after the last inoculation. By comparison with viable counts for CH or BC
      alone, we estimated the potentiating effects of dibasic acid diester on the
      bactericidal activity of CH or BC, and confirmed that this activity of the two
      disinfectants was potentiated in the presence of certain compounds in the
      homologs of di-n-butyl esters of aliphatic dibasic acid, and di-alkyl esters of
      adipic and phthalic acid. Diisobutyl adipate, one of the most effective diesters,
      substantially enhanced the bactericidal activities of benzethonium chloride,
      cetyl pyridinium chloride and didecyl dimethyl ammonium chloride, as well as CH
      and BC, but not those of polyhexamethylene biguanide or alkyldiaminoethyl
      glycinate. The potentiating effects of dibasic acid diesters observed for both CH
      and BC seemed to be affected by the hydrophobic character of these diesters
      themselves and are also expressed well by a particular quadratic equation as a
      function of these characters: namely, capacity factors, as determined by high
      performance liquid chromatography.

PMID- 1394652
TI  - Isolation of 1-beta-D-arabinofuranosylcytosine from the mushroom Xerocomus
      nigromaculatus Hongo.

PMID- 1394653
TI  - Purines. LII. Synthesis and biological evaluation of 8-methylguanine 7-oxide and
      its 9-arylmethyl derivatives.
AB  - The synthesis of 8-methylguanine 7-oxide (3) was accomplished via a
      "phenacylamine route", which started from condensation of alpha-(4
      methoxybenzylamino)propiophenone (6), prepared by coupling of alpha
      bromopropiophenone (4) and 4-methoxybenzylamine (5), with 2-amino-6-chloro-5
      nitro-4(3H)-pyrimidinone (7) and proceeded through cyclization of the resulting
      phenacylaminopyrimidinone (8) and removal of the 4-methoxybenzyl group. The N
      oxide 3 and its 9-arylmethyl derivatives 9 and 11 showed only very weak
      antileukemic activity and no antimicrobial activity.

PMID- 1394654
TI  - Enzyme labeling in steroid enzyme immunoassays. The p-nitrophenyl ester method
      for alkaline phosphatase and glucose oxidase labelings.
AB  - The p-nitrophenyl ester method was assessed as an enzyme labeling technique. The
      active ester of a carboxylated testosterone derivative was treated with alkaline
      phosphatase and glucose oxidase to give labeled antigens, using various molar
      ratios of steroid to enzyme. Satisfactory immunoreactivities with an anti
      testosterone antibody in an enzyme immunoassay system were obtained with the
      labeled antigens prepared at pH 8.5 by the use of molar ratios higher than 30 and
      10, respectively, in the alkaline phosphatase and glucose oxidase labelings.

PMID- 1394655
TI  - Gas phase derivatization of ammonia with 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole
      and its application to urease assay.
AB  - An ammonia-specific and rapid fluorometric method for determination of ammonia
      and urease activity was developed. The method is designed to assay ammonia levels
      or urease activity for the rapid diagnosis of Helicobacter pylori infection. 4
      Fluoro-7-nitrobenzo-2-oxa-1,3-diazole was used to derivatize ammonia and 4-amino
      7-nitrobenzo-2-oxa-1,3-diazole was analysed by high performance liquid
      chromatography at an excitation wavelength of 455 nm and an emission wavelength
      of 520 nm. Derivatization was designed to react with ammonia gas produced in a
      strong alkaline pH sample. The fluorescent intensity was linear in the range of
      0.1-10 mM ammonia per tube when the reaction was carried out for 15 min at 37
      degrees C. Urease activity, judged as the amount of ammonia production from urea,
      could be measured at 25 ng per tube (S/N = 1.5) with Jack bean meal urease.
      Because of its rapidity, this assay is potentially superior to the current
      standard method in use in clinical settings.

PMID- 1394656
TI  - Effect of tetrahydropyranyladriamycin (THP-ADR) and 4'-epiadriamycin (4'-epi-ADR)
      on lipid peroxide levels in mice.
AB  - Lipid peroxide levels were measured in mouse tissues to study their relation to
      the cardiotoxicity of anthracyclines. The effects of tetrahydropyranyladriamycin
      (THP-ADR) and 4'-epiadriamycin (4'-epi-ADR), which are less cardiotoxic than
      adriamycin (ADR), were examined. Neither THP-ADR nor 4'-epi-ADR increased the
      lipid peroxide levels in the heart, however, both increased reduced nicotinamide
      adenine dinucleotide phosphate (NADPH)-dependent lipid peroxidation in mouse
      liver and lung microsomes, to the same degree as ADR. Therefore, the results
      obtained in vitro were not the same as those obtained in vivo. Of all of the
      anthracyclines tested, only THP-ADR increased the lipid peroxide levels in the
      lung. Thus, THP-ADR may be pulmotoxic. Differences in the activities of
      glutathione peroxidase and glutathione S-transferase reflected the differences in
      lipid peroxide levels.

PMID- 1394657
TI  - Effect of bacteriohopane-32-ol on lipid metabolism in Hep G2 cells.
AB  - To investigate the biological activity of the hopane group of pentacyclic
      triterpenes, the effect of bacteriohopane-32-old (Monol) on lipid synthesis and
      secretion was determined using Hep G2 cells. Despite its structural similarity to
      25-hydroxycholesterol, Monol did not affect free and esterified cholesterol
      synthesis determined by the incorporation from [14C]acetate. Monol reduced the
      phospholipid secretion from Hep G2 cells without affecting cellular phospholipid
      synthesis from [3H]glycerol. It also decreased the secretion of apolipoprotein B.
      These results suggest that the Monol-induced reduction in phospholipid secretion
      is due to a decrease in the number of lipoprotein particles secreted from Hep G2
      cells.

PMID- 1394658
TI  - Influence of time of administration of a Shosaiko-to extract granule on blood
      concentration of its active constituents.
AB  - Using a Shosaiko-to extract granule, we investigated the effects of the timing of
      administration (orally, before and after a meal) on the plasma concentration of
      its active constituents, glycyrrhizin (GL), baicalin, baicalein and glycyrrhizic
      acid (GA), a metabolite of GL. The pattern of plasma concentration change of GL
      differed between the two times of administration, and followed a two-phase
      pattern when the granules were taken before meals. There was no difference
      neither in the area under the plasma concentration-time curve (AUC) between the
      two periods, nor AUC itself. GA showed no difference in plasma concentration
      pattern, nor was baicalin detected in the plasma following administration by
      either method. The plasma concentration pattern of baicalein differed between the
      two timings but followed that of the two-phase pattern in each case. The plasma
      concentration pattern of active constituents of Shosaiko-to extract granule
      varied with the time of administration, but there was no significant difference
      in the maximum plasma concentration or AUC of active constituents depending on
      the administration. We concluded that the present clinical timing of
      administration of Shosaiko-to should be determined on the basis of patient
      compliance and other relevant factors.

PMID- 1394659
TI  - Prodrugs of 2',3'-dideoxyinosine (DDI): improved oral bioavailability via
      hydrophobic esters.
AB  - Five ester prodrugs of 2'3'-dideoxyinosine (DDI) were synthesized for the purpose
      of improving oral bioavailability. The prodrugs, acetate (C2-DDI), octanoate (C8
      DDI), stearate (C18-DDI), benzoate (Bz-DDI), and hemisuccinate (Suc-DDI) were
      proved to quantitatively regenerate their parent drug by enzymatic hydrolysis.
      Though the chemical stability of the prodrugs under acidic conditions was not
      improved, their solubility in water was significantly decreased by
      esterification, except for Suc-DDI. Bioavailability was evaluated by oral
      administration to rats. Two hydrophobic prodrugs (C8-DDI and Bz-DDI) showed
      higher absolute bioavailability (23.5% and 31.0%, respectively) than did DDI
      (15.2%), though that of C2-DDI (11.5%) and Suc-DDI (4.5%) was poor.

PMID- 1394661
TI  - Synthesis and aldose reductase inhibitory activity of triazine derivatives
      possessing acetic acid group.
AB  - N-Acetic acid derivatives of 6-aryl-pyrazolo-triazin-4-ones were synthesized for
      evaluation as new aldose reductase inhibitors. The intrinsic activity of each
      compound was assessed by measuring the inhibition of enzymatic activity in an
      isolated pig lens enzyme preparation. All the prepared compounds exhibited a
      significant in vitro aldose reductase inhibitory effect (10(-6) M less than or
      equal to IC50 less than or equal to 10(-4) M). Furthermore, biological activity
      (log 1/IC50) for most of the data sets could be correlated directly to electronic
      and steric parameters. Finally, spatial configuration of the most active
      derivative 6c (IC50 = 2 x 10(-6) M) was compared with that of tolrestat and with
      pharmacophor requirements of the aldose reductase inhibitor site using a
      molecular modeling system.

PMID- 1394660
TI  - New antitumor bicyclic hexapeptides, RA-XI, -XII, -XIII and -XIV from Rubia
      cordifolia.
AB  - Four new bicyclic hexapeptides, named as RA-XI, -XII, XIII and -XIV were isolated
      from Rubia cordifolia and showed potent antitumor activities against P-388. The
      structures were elucidated from spectroscopic and chemical evidences. RA-XII,
      XIII and -XIV were proved to be unique bicyclic hexapeptidic glucosides.

PMID- 1394662
TI  - Agents for the treatment of overactive detrusor. III. Synthesis and structure
      activity relationships of N-(4-amino-2-butynyl)acetamide derivatives.
AB  - A series of N-(4-amino-2-butynyl)acetamides were synthesized and examined for
      their inhibitory activity on detrusor contraction and mydriatic activity as an
      index of anticholinergic side effect. Among those compounds synthesized, (+)-2
      cyclohexyl-N-(4-dimethylamino-2-butynyl)-2-hydroxy-2-phenylacet amide
      hydrochloride ((+)-13b.HCl), 2-cyclohexyl-2-hydroxy-N-(4-methylamino-2-butynyl)-2
      phenylacetamide+ ++ hydrochloride (13c.HCl), N-(4-dimethylamino-2-butynyl)-2,2
      diphenyl-2-hydroxyacetamide hydrochloride (14a.HCl), and 2,2-diphenyl-N-(4
      ethylamino-2-butynyl)-2-hydroxyacetamide hydrochloride (14b.HCl) showed
      equipotent inhibitory activity on detrusor contraction to oxybutynin (1) and less
      mydriatic activity. Further evaluation of these compounds as an agent for the
      treatment of overactive detrusor has been examined.

PMID- 1394663
TI  - Studies on cerebral protective agents. I. Novel 4-arylpyrimidine derivatives with
      anti-anoxic and anti-lipid peroxidation activities.
AB  - Novel 4-arylpyrimidine derivatives were synthesized by the oxidation of 4-aryl
      1,4-dihydropyrimidines, and their effects on anti-anoxic (AA) activity in mice
      and anti-lipid peroxidation (ALP) activity in rat brain mitochondria were
      investigated. Among these compounds, ethyl 6-methyl-2-phenyl-4-(4-pyridyl)-5
      pyrimidinecarboxylate (4b) has AA activity (10 mg/kg, i.p.) and ethyl 6-methyl-4
      (3-nitrophenyl)-2-phenyl-5-pyrimidinecarboxylate (4f) has ALP activity (73%
      inhibition at 10(-5) g/ml). The latter compound (100 mg/kg, i.p.) was also
      effective on arachidonate-induced cerebral edema in rats with comparable potency
      to that of vitamin E.

PMID- 1394664
TI  - Novel benzamides as selective and potent gastrokinetic agents. IV. Synthesis and
      structure-activity relationships of 2-substituted 4-amino-N-[(4-benzyl-2
      morpholinyl)methyl]-5-chlorobenzamides.
AB  - A new series of 2-substituted 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5
      chlorobenzamides (4-39) including a few 4-fluorobenzyl analogues were prepared
      and evaluated for their gastrokinetic activity by determining their effects on
      the gastric emptying activity of phenol red semisolid meal in rats. The C-2
      substituent comprises alkoxy and variously substituted alkoxy groups. Among the
      derivatives, 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-2-(n-butoxy)-5
      chlorobenza mide (5), its 4-fluorobenzyl (6), and 3-methyl-2-butenyloxy analogues
      (22) were superior to cisapride and essentially equipotent to the 2-ethoxy
      analogue (1b, AS-4370 as its citrate) in gastrokinetic activity. These compounds,
      like AS-4370, had no dopamine D2 receptor antagonistic activity.

PMID- 1394665
TI  - Synthesis of the optically active trans-isomers of diltiazem and their
      cardiovascular effects and Ca-antagonistic activity.
AB  - Optically active trans-isomers of diltiazem were synthesized and their
      cardiovascular effects were evaluated in anesthetized dogs and in isolated guinea
      pig hearts. Both (+)-2 (2R,3S) and (-)-2 (2S,3R) were much less active than
      diltiazem (1, 2S,3S) with short duration of action. No substantial enantiomeric
      difference in activity was seen between them. Their Ca-antagonistic activities on
      Ca(2+)-induced contractions in K(+)-depolarized canine basilar arteries were also
      examined. Absolute stereochemistry of (+)-2 was determined to be 2R,3S by X-ray
      crystallographic analysis.

PMID- 1394666
TI  - Synthesis and antitumor activity of fused quinoline derivatives. III. Novel N
      glycosylamino-indolo[3,2-b]quinolines.
AB  - Novel indolo[3,2-b]quinolines (1b-k), having a nitro, amino, acetamido,
      methanesulfonamido, or glycosylamino group at the 2, 7, or 8-position, were
      prepared and their antitumor activities against P388 leukemia in mice were
      examined. The 7-galactopyranosylamino derivative (1g) showed the most potent
      activity (optimal dose = 25 mg/kg, T/C greater than 333%, cure rate 5/6).

PMID- 1394667
TI  - Imidazo[1,2-alpha]pyridines. III. Synthesis and bradycardic activity of new 5
      imidazo[1,2-alpha]pyridin-6-ylpyridine derivatives.
AB  - Structural modification of the cardiotonic agent, loprinone (E-1020, 1),
      suggested by data that it has a less positive chronotropic effect than milrinone
      (15), led us to find novel bradycardic agents that were structurally different
      from homoveratryl amine derivatives. Alkyl-oxy, -thio, and -amino derivatives at
      the 2-position of the pyridine ring of 1 produced bradycardic activity without a
      significant effect on blood pressure and myocardial contractility. Aryloxy
      analogues also decreased heart rate, and members with an electron-withdrawing
      group at the ortho position of the phenyl ring showed higher activity.
      Replacement of the imidazo[1,2-alpha]pyridine with pyridine resulted in
      diminished activity. The mechanism of bradycardic activity of these compounds
      seems to be direct action on the sinus node.

PMID- 1394668
TI  - Contractile activity of porcine neuromedin U-25 and various neuromedin U-related
      peptide fragments on isolated chicken crop smooth muscle.
AB  - Contractile activity of porcine neuromedin U-25 (p-NMU-25) and various neuromedin
      U (NMU) peptide fragment amides was examined on chicken crop smooth muscle
      preparation. The relative activity (expressed as RA value) of p-NMU-25 to porcine
      neuromedin U-8 (p-NMU-8) was 5.51 +/- 0.09, and p-NMU-25 (15-25) was the most
      potent fragment with an RA value of 7.78 +/- 0.05. All C-terminal 11-peptide
      amides of rat, rabbit, and frog NMU peptides retained activity about three-fold
      higher than the corresponding C-terminal 8-peptide amides. The peptide segment
      Asn15-Arg-Arg17 of p-NMU-25, as well as the corresponding positions of various
      NMU peptides: Ser13-Gly-Gly15 of rat NMU and Ser15-Arg-Gly17 of rabbit and frog
      NMUs, appeared to be involved in the structural requirements for increased
      contractile activity in the assay system.

PMID- 1394669
TI  - The mutagenic constituents of Rubia tinctorum.
AB  - Twenty compounds were isolated from the roots of Rubia tinctorum which are used
      as a commercial source of madder color. Among these compounds, mollugin (1), 1
      hydroxy-2-methylanthraquinone (2), 2-ethoxymethylanthraquinone(11), rubiadin
      (13), 1,3-dihydroxyanthraqunone (14), 7-hydroxy-2-methylanthraquinone (16),
      lucidin (17), 1-methoxymethylanthraquinone (18) and lucidin-3-O-primeveroside
      (19) showed mutagenicity with Salmonella typhimurium TA 100 and/or TA 98. Since
      the mutagenic compounds isolated are anthraquinone derivatives with the exception
      of compound 1, structure-mutagenicity relationships of the anthraquinones were
      also studied. The results suggested that the greatest activity is exhibited by
      1,3-dihydroxyanthraquinones possessing methyl or hydroxylmethyl group on carbon
      2.

PMID- 1394670
TI  - Selected ion monitoring for the determination of bromovalerylurea in human
      plasma.
AB  - A gas chromatography-selected ion monitoring procedure with chemical ionization
      is described for the determination of bromovalerylurea (BVU) in human plasma. BVU
      was extracted with ether after addition of 2-bromo-2-methylpropylurea as an
      internal standard. The lower limit of BVU quantification by this method was 2
      ng/0.1 ml plasma volume. This procedure was used to determine the sequential
      plasma levels of BVU in a human volunteer following a single oral dose of a
      commercial analgesic.

PMID- 1394671
TI  - Production and specificity of anti-22-oxacalcitriol antisera.
AB  - 22-Oxacalcitriol 3-hemiglutarate, a haptenic derivative of 22-oxacalcitriol, was
      synthesized to obtain a specific antibody for use in radioimmunoassay. Three
      antisera were elicited in rabbits against the hapten conjugated with bovine serum
      albumin, and their specificity was examined by cross-reaction study. One of the
      antisera was found to be satisfactorily specific, and expected to provide a
      radioimmunoassay useful for the pharmacokinetic study of 22-oxacalcitriol.

PMID- 1394672
TI  - Colorimetric assay for lysozyme using Micrococcus luteus labeled with a blue dye,
      Remazol brilliant blue R, as a substrate.
AB  - Micrococcus luteus (M. lysodeikticus) labeled with Remazol brilliant blue R (blue
      ML) was prepared as a novel substrate for the colorimetric assay of lysozyme. The
      treatment of the labeled substrate with lysozyme resulted in the release of
      soluble blue products which can be easily measured spectrophotometrically at 600
      nm. The blue color was most efficiently released at pH 7 and ionic strength of
      0.2 on incubation with hen lysozyme at 40 degrees C. A new colorimetric method
      for the assay of lysozyme using this substrate was developed. The assay system
      gave a linear dose-response curve, and as little as 0.1 microgram of human
      lysozyme (1 microgram/ml, 100 microliters) can be detected. The present method is
      more convenient and reproducible than the conventional lysozyme assay with
      bacterial cells. Application of the system to the determination of lysozyme in
      human serum is described.

PMID- 1394673
TI  - Solubilization of limulus test reactive material(s) from Candida cells by murine
      phagocytes.
AB  - Solubilization of limulus test reactive materials from Candida was examined in
      the presence or absence of phagocytic cells. Solubilized limulus test reactive
      materials (LTRM) were detected in culture supernatant, and hot water and sodium
      hydroxide extracts of the acetone dried cells of Candida parapsilosis.
      Suspensions of Candida cells also reacted with limulus test, and LTRM were
      released from the acetone dried cells by serum treatment. After treatment of the
      acetone dried cells with polymorphonuclear leucocytes (PMN) or macrophages (M
      phi), a significant amount of LTRM was solubilized. Significant amounts of LTRM
      were also released by PMN during treatment of live and growing C. parapsilosis.
      The reactivity of LTRM was completely inhibited by the addition of excess amount
      of purified (1----3)-beta-D-glucan, suggesting LTRM from Candida cells as
      described above would contain (1----3)-beta-D-glucan. These results suggested
      that LTRM during fungal infection would come from the extracellular water soluble
      polysaccharide fraction as well as the insoluble cell wall fraction solubilized
      by the action of phagocytes.

PMID- 1394674
TI  - Biopolymers from marine invertebrates. XIII. Characterization of an antibacterial
      protein, dolabellanin A, from the albumen gland of the sea hare, Dolabella
      auricularia.
AB  - An antibacterial factor, dolabellanin A, was purified from the albumen gland of a
      sea hare, Dolabella auricularia. Purified dolabellanin A was a glycoprotein of
      250 kilodaltons consisting of 4 subunits, and showed both antibacterial and
      antineoplastic activities. The two activities were lost in parallel on heating
      and at low and high pH. This factor was half-maximally active for gram-positive
      and -negative bacteria at 0.018-0.48 microgram/ml, and its action was not
      bactericidal but bacteriostatic. Dolabellanin A did not induce morphological
      elongation of bacteria or the release of adenosine triphosphate, but it
      completely inhibited the syntheses of deoxyribonucleic acid (DNA) and ribonucleic
      acid by E. coli within 6 min. These results suggest that dolabellanin A, which is
      found in a marine invertebrate, the sea hare, is a new antibacterial protein, and
      that it exerts its action by inhibiting nucleic acid synthesis, as does a DNA
      inhibiting chemotherapeutic drug.

PMID- 1394675
TI  - Oily drug carriers in cancer chemotherapy. II. Preparation of viscous ethyl
      oleate for intraarterial infusion therapy and its disposition in rats and
      hamsters.
AB  - Viscous ethyl oleate (VEO) was prepared as an oil drug carrier by the addition of
      aluminum stearate or ethyl cellulose. Since the rate of shear of VEO containing
      aluminum stearate was greatly and nonlinearly changed against the shearing stress
      compared to that containing ethyl cellulose, the latter was used for subsequent
      microvascular and organ distribution experiments in rats and hamsters. For
      infusion into the carotid artery in hamsters, neat ethyl oleate (EO, 4cP) or VEOs
      of various apparent viscosities (40, 80, 120 cP-VEOs) embolized the vascular
      system in the cheek pouch, although arrival time to the site where the
      embolization was observed and the embolization period differed depending on the
      type of oily drug carrier. For infusion into the hepatic artery in rats, however,
      only 120 cP-VEO embolized the vascular system in the liver. After infusion of the
      oily drug carrier containing 3H-oleic acid into the artery of hamster cheek pouch
      and rat liver, 30-50% of the radioactivity was gradually eliminated within 48 h,
      whereas about 80% of the dose was rapidly eliminated after infusion to rat
      stomach and kidney. In addition, the amount of 120 cP-VEO remaining in each organ
      48 h after infusion was higher than those of EO and 40 and 80 cP-VEOs.
      Histological observation after infusion in rat liver revealed that 120 cP-VEO
      slowly migrated from the artery or arteriole to the sinusoidal capillary region.
      These results suggest that 120 cP-VEO can be used as a drug carrier because of
      its function of vascular embolization and high retention in a targeted tissue.

PMID- 1394676
TI  - Thermodynamic aspects of fatty acids binding to human serum albumin: a
      microcalorimetric investigation.
AB  - Thermodynamic parameters have been evaluated for the binding interaction between
      human serum albumin (HSA) and unbranched fatty acids (FFA) on the basis of a flow
      microcalorimetric measurement at pH 7.4 and 37 degrees C by computer-fitting to
      single- and two-class binding models. The heat of binding increased
      exothermically with increasing alkyl chain length. FFA with nine or less carbons
      bound to only one class of binding sites (n = 2) with a binding constant (K) of
      10(4) M-1. FFA with ten or more carbons bound to the first class of binding sites
      with high affinity K in the older of 10(5) to 10(6) M-1, and to the second class
      with a lower affinity and high capacity. The free energy change of the first
      class of binding sites (delta G1) became more negative as the chain length of FFA
      was increased. The enthalpy change per mol of FFA (delta H) decreased at the rate
      of -7.47 kJ.mol-1.CH-1(2) to a minimum at C9 and then increased due to the
      hydrophobicity of alkyl chains. Compensation analysis for the i th class of HSA
      molecule by plotting molar changes of enthalpy (delta Hmi) against entropy (delta
      Smi) and free energy (delta Gmi) indicates two distinct binding sites. The first
      class (i = 1) of the long-chain FFA on HSA is an entropy-driven reaction
      associated with nearly constant values of delta Hm1 (-43.0 +/- 4.8 kJ.mol-1),
      slightly negative values of delta Sm1 (-47.4 less than or equal to delta Sm1 less
      than or equal to -8.1 J.mol-1.K-1) and -delta Gm1 values, increasing with
      increasing alkyl chain length. The second class (i = 2) of the long-chain FFA may
      lie in the same region as the binding sites of the short- and medium-chain FFA
      with a linear relationship between delta Hmi-delta Smi.

PMID- 1394678
TI  - Laser diffraction estimation of particle size distribution of slightly water
      soluble drugs coexisting with additives: application to solid dosage forms.
AB  - A simple and quantitative evaluation method for particle size distribution
      (fx(r)) of slightly water-soluble drugs dispersed in an aqueous medium together
      with other water-insoluble additives was developed using a laser diffraction
      method. The particle size distribution function of the powder mixture, (f(r)),
      was assumed as f(r) = phi x.fx(r) + phi a.fa(r), where phi is the volume fraction
      of each component dispersed in a measurement medium and fa(r) is the distribution
      function of another water-insoluble additive "a". In order to calculate fx(r)
      from f(r), it is necessary to know the density of drug and additive in the
      measurement medium, d(x) and d(a), but this is difficult to determine since
      particles usually swell in the medium. Thus, a method was developed to use their
      relative value, delta a (= da/dx). As a practical application, oxolinic acids
      (OA) of three sizes (OA-S (about 2 microns), OA-M (about 7 microns) and OA-L
      (about 24 microns)) were used as model drugs. delta a values were determined for
      various additives using the mixture of OA-S and each additive. Then, using delta
      as, fx(r) of OA-M or OA-L in the mixture containing OA-M or OA-L and additives
      was calculated from the f(r) experimentally determined for the mixture. They
      agreed well with their original distributions. The method was applied to some
      dosage forms, and the results obtained had good correlation with those from
      turbidity, wet sieving or dissolution test.

PMID- 1394677
TI  - Effect of glycyrrhizinate on dissolution behavior and rectal absorption of
      amphotericin B in rabbits.
AB  - The effects of dipotassium glycyrrhizinate (GLYK) on the dissolution behavior and
      bioavailability of amphotericin B (AMB) were investigated. The mixtures of AMB
      and GLYK were prepared at different molar ratios by lyophilization.
      Lyophilization resulted in amorphous AMB either alone or in the mixture.
      Dissolution rates of AMB of the mixtures were markedly faster than that of
      lyophilized AMB alone, which was followed by a decrease of dissolution. The
      initially-enhanced dissolution rate was likely to be due to the improvement of
      surface wettability of drug particles with GLYK rather than the amorphous state
      of AMB. A phase solubility study of AMB with GLYK indicated that the increasing
      solubility was caused by micellar solubilization. The in vitro release rate of
      AMB from suppositories containing the lyophilized mixtures was significantly
      accelerated by increasing the amount of GLYK. The rectal absorption of AMB from
      suppositories containing either the drug alone, a physical mixture or a
      lyophilized mixture was studied using rabbits. The absorption of the mixture
      (AMB/GLYK = 1/9) was about 35 times greater in the area under the serum
      concentration-time curve (0-24 h) than that of lyophilized AMB alone. These
      results suggest that GLYK is useful for improving the dissolution property of AMB
      and the bioavailability of the drug incorporated in suppositories.

PMID- 1394679
TI  - Permeability of insulin entrapped in liposome through the nasal mucosa of
      rabbits.
AB  - The permeability of liposome entrapping insulin through the nasal mucosa of
      rabbit has been studied and compared with the permeability of insulin solution
      with or without pretreatment by sodium glycocholate (GC). Insulin entrapped in
      liposome was not detected in the receiver cell using the diffusion cells with the
      nasal mucosa. On the other hand, permeability of insulin entrapped in liposome
      increased after the pretreatment of GC. The phospholipids which result from
      liposomes, were not observed in the receiver. Also, the GC remaining in the nasal
      mucosa was measured. Considering the mechanism of permeation of insulin entrapped
      in liposome through the nasal mucosa, the GC remaining in the nasal mucosa may
      cause the lysis of liposomes.

PMID- 1394680
TI  - Decomposition of linear dodecylbenzenesulfonate by simultaneous treatment with
      ozone and ultraviolet irradiation: rapid disappearance of formed mutagens.
AB  - The decomposition products and mutagenic activity in Salmonella typhimurium
      strains TA98, TA100 and TA104 in the presence and absence of S9 mix of linear
      dodecylbenzenesulfonate (DBS) in aqueous solution after ozone treatment alone or
      simultaneous treatment with ozone and ultraviolet (UV) irradiation (ozone/UV
      treatment) were investigated. The decomposed DBS solutions after these treatments
      for 4 h were mutagenic for strains TA98, TA100 and TA104 both with and without S9
      mix, but this mutagenicity disappeared rapidly during further ozone/UV treatment.
      Mutagenicity of the decomposed solution of DBS, however, was not substantially
      decreased by treatment with ozone alone. Formaldehyde and glyoxal were identified
      as the decomposition products of DBS in water by high-performance liquid
      chromatography after treatment with 2,4-dinitrophenylhydrazine. Although these
      two compounds were mutagenic for strain TA104 both with and without S9 mix, they
      disappeared after further ozone/UV treatment but not after ozone treatment alone.
      These results indicate that ozone/UV treatment is an effective procedure for
      purifying drinking water.

PMID- 1394681
TI  - Synthesis, structure and antitumor activity of a water-soluble platinum complex,
      (1R,3R,4R,5R)-(-)-quinato(1R,2R-cyclohexanediamine)platinum (II).
AB  - The reaction of dihydroxo(1R,2R-cyclohexanediamine)platinum(II) with (-)-quinic
      acid gave a water soluble complex, (-)-quinato(1R,2R
      cyclohexanediamine)platinum(II). The crystal structure of the complex was
      determined by X-ray analysis. The data indicate a chelation of the alpha
      hydroxycarboxylic acid part of quinic acid to platinum(II). The complex shows
      moderate antitumor activity against murine leukemia L1210 at high doses (T/C x
      100 = 179% at a dose of 200 mg/kg).

PMID- 1394682
TI  - Synthesis and biological activities of 1-[2-(dimethylamino)ethyl]- and 1-[3
      (dimethylamino)propyl]-substituted 3-methyl-1,8-dihydrocycloheptapyrazol-8-ones
      and related compounds.
AB  - 3-Methyl-1,8-dihydrocycloheptapyrazol-8-ones (2a-c), prepared from 3
      acetyltropolones (1a-c), were treated with diazomethane, methyl iodide, dimethyl
      sulfate, and diethyl sulfate to give 1- and 2-alkylated compounds. The 1,8
      dihydrocycloheptapyrazol-8-one (2a) also reacted with 2-(dimethylamino)ethyl, 2
      (diethylamino)ethyl, 3-(dimethylamino)propyl, and 2,3-dihydroxypropyl chloride to
      afford the corresponding 1-substituted products. A preliminary study was made of
      the biological activities of some of the obtained compounds.

PMID- 1394683
TI  - Studies on angiotensin converting enzyme inhibitors. VI. Synthesis and
      angiotensin converting enzyme inhibitory activities of the dicarboxylic acid
      derivative of imidapril and its diastereoisomers.
AB  - All possible diastereoisomers of the dicarboxylic acid (10a), the biologically
      active form of imidapril (1), were synthesized, and their inhibitory activity
      against angiotensin converting enzyme (ACE) was examined. The in vitro ACE
      inhibitory activity of these compounds greatly depended on the configurations of
      the three asymmetric carbons in each molecule. The (S,S,S) isomer (10a) showed
      much more potent activity than the others.

PMID- 1394684
TI  - Effects of anti-epileptic drugs on the L-tryptophan binding to human serum
      albumin.
AB  - Effects of four anti-epileptic drugs (AED; phenobarbital, phenytoin,
      carbamazepine and sodium valproate) on the L-tryptophan binding to human serum
      albumin were studied. Among these drugs examined, only sodium valproate inhibited
      the binding even within the concentrations of its therapeutic range, and the
      Klotz plotting analysis revealed that the inhibition was competitive. The results
      of examinations with sera from epileptic patients medicated with these AED and
      drug-free normal controls also suggested that the protein binding ratios of L
      tryptophan were decreased in the blood plasma of some patients with the high
      valproate concentrations and the low albumin contents.

PMID- 1394685
TI  - Application of poly-L-lysine to purification of leukocyte cathepsin G by affinity
      chromatography.
AB  - Poly-L-lysine with molecular masses of 3.3-290 kDa increased the amidolytic
      activities of leukocyte elastase and cathepsin G at low concentration, but had
      little effect on the activities of pancreatic elastase, alpha-chymotrypsin,
      plasmin and thrombin. Highly purified cathepsin G was obtained from column of EAH
      Sepharose 4B or Suc-L-Tyr-D-Leu-D-Val-pNA-Sepharose (affinity chromatography) by
      elution with poly-L-lysine solution (0.4 mg/ml, molecular weight (MW.) 290000 or
      2.2 mg/ml, MW. 3300). Leukocyte elastase, adsorbed to Suc-L-Tyr-D-Leu-D-Val-pNA
      Sepharose, was not eluted with poly-L-lysine solution. The amino acid composition
      of purified cathepsin G has been determined.

PMID- 1394686
TI  - Biopolymers from marine invertebrates. XII. A novel cytolytic factor from a
      hermit crab, Clibanarius longitarsus.
AB  - Bioactive polymers were sought in marine arthropoda and a novel cytolytic factor
      was found in a hermit crab, Clibanarius longitarsus. The partially purified
      factor showed activity in fractions corresponding to a molecular weight of about
      10 kilodaltons on a Sephadex G-75 column. This cytolytic factor was halfmaximally
      active for tumor cells at 0.13-0.66 micrograms/ml and for normal cells at 1.9-82
      micrograms/ml. Tumor lysis by the factor was time dependent and was complete
      within 12 h. This bioactive polymer was labile on heating, at low and high pH.

PMID- 1394687
TI  - Bacteriostatic effect of 4,7-dicyanobenzofurazan due to inactivation of 2,3
      dihydroxyisovalerate dehydratase.
AB  - As part of our research on benzofurazans (BZs), we have reported the bacterioses
      of BZs in Escherichia coli, which may be due to O2-. produced within E. coli in
      the presence of dioxygen (O2). Incubation of E. coli with 4,7-dicyanobenzofurazan
      (1) lowered the 2,3-dihydroxyisovalerate dehydratase activity detectable in
      extracts from these cells. Addition of branched chain amino acids such as valine
      and leucine protected E. coli from growth inhibition by compound 1, though it
      could not protect E. coli from the damage by paraquat (PQ). Addition of Fe(III)
      tris[N-(2-pyridylmethyl)-2-aminoethyl]amine (Fe-TPAA), a novel superoxide
      dismutase mimic, protected the dehydratase in a dose-dependent manner, which
      confirms that inactivation of the dehydratase is largely due to production of O2
      .. The possibility was discussed that the bacteriostatic effect of compound 1 is
      due to the inactivation of 2,3-dihydroxyisovalerate dehydratase.

PMID- 1394688
TI  - Preparation of (22S)- and (22R)-24-homo-26,26,26,27,27,27-hexafluoro-1,22,25
      trihydroxy-24- yne-vi tamin D3.

PMID- 1394689
TI  - Pharmacokinetics of brain natriuretic peptide in rats.
AB  - The pharmacokinetics of rat brain natriuretic peptide (rBNP) was compared with
      that of alpha-rat atrial natriuretic peptide (alpha-rANP) in rats. After
      intravenous infusion in rats (600 pmol min-1kg-1 for 2 min), the disappearance of
      plasma rBNP was 4-fold slower than that of alpha-rANP. The estimated mean plasma
      clearance rates for rBNP and alpha-rANP were 45.9 ml min-1kg-1 and 74.4 ml min
      1kg-1, respectively. The affinity of rBNP for the clearance receptor or
      degradation enzyme was considered to be lower than that of alpha-rANP.

PMID- 1394690
TI  - Site-specific cleavage of glycated human serum albumin in the presence of iron.
AB  - Nonenzymatically glycated human serum albumin was incubated with ferric ion at 37
      degrees C in 0.2 M phosphate buffer, pH 7.4, up to 30 days. In the incubation
      mixture, amino acids, tyrosine and phenylalanine, were detected, suggesting site
      specific cleavage of glycated human serum albumin.

PMID- 1394691
TI  - pH-inducible beta-glucosidase and beta-glucuronidase of intestinal bacteria.
AB  - beta-Glucosidase and beta-glucuronidase of human and rat fecal bacteria were
      induced by cultivation in alkaline media although their growths were not
      affected. When a bacterium isolated from human feces producing each enzyme was
      cultured in a medium at pH 5 for 12-15 h and then adjusted to pH 8, beta
      glucosidase and beta-glucuronidase were induced 9.2-fold and 11.5-fold,
      respectively.

PMID- 1394692
TI  - The enantioselective metabolism of p-cymene in rabbits.
AB  - p-Cymene (1) was metabolized in rabbits and the following four optically active
      metabolites, 2-(p-tolyl)-1-propanol (3': R/S = 65:35), 2-(p-tolyl)propanoic acid
      (5': R/S = 0:100), p-(2-hydroxy-1-methylethyl)benzoic acid (6': R/S = 91:9) and p
      (1-carboxyethyl)benzoic acid (8': R/S = 30:70), were isolated in addition to
      three optically inactive metabolites, 2-(p-tolyl)-2-propanol (2), p
      isopropylbenzoic acid (4'), and p-(1-hydroxy-1-methylethyl)benzoic acid (7'). The
      presumed metabolic pathways of p-cymene in rabbits were confirmed by the
      administration of the intermediate metabolites (2, 3', 4', and 5'). The
      enantiomeric ratios of the metabolites, 3' and 6', suggested that omega
      hydroxylations of the isopropyl group in 1 and 4' occurred preferentially at the
      pro-S methyl group. In the metabolism of 1, the S-isomers are predominant in the
      propanoic acid derivatives, but the R-isomers are rich in the propanol
      derivatives. It is of interest that the metabolism of 4', however, produced
      predominantly the corresponding propanol derivative (6'; R/S = 91:9) and
      propanoic acid derivative (8'; R/S = 80:20) possessing the same R-configuration.
      Some optically active p-cymene derivatives were also synthesized as standard
      compounds.

PMID- 1394693
TI  - Preparation and antitumor activity of 2''-O-, 3''-O- and 2'',3''-di-O-substituted
      derivatives of etoposide.
AB  - The 2''-O-, 3''-O- and 2'',3''-di-O-substituted derivatives (4a--p) of etoposide
      were prepared by nucleophilic substitution of 4'-O-benzyloxycarbonyletoposide (2)
      followed by deprotection. Controlled reaction (a limited amount of reagents and
      low temperature) was required for preparing the mono-O-substituted derivatives.
      In terms of ED125 values, doses which show 125% of T/C against P388 leukemia in
      mice, both the 2''-O-acetate (4a, ED125 = 0.18 mg/kg) and 3''-O-acetate (4b, 0.23
      mg/kg) were nearly as active as etoposide (1, 0.19 mg/kg), while the 2'',3''-di-O
      acetate (4c, 1.9 mg/kg) was somewhat less potent. In the replacement with other
      substituents, antitumor activity of the 2''-O-substituted derivatives was
      affected much more by the difference of the substituents as compared with that of
      the corresponding 3''-O-substituted derivatives. In the 2'',3''-di-O-substituted
      derivatives, the activity was decreased additively on the substituents.

PMID- 1394694
TI  - Synthesis and evaluation of iodinated benzamide derivatives as selective and
      reversible monoamine oxidase B inhibitors.
AB  - A new series of iodinated analogues of N-(2-aminoethyl)benzamide was synthesized
      and evaluated for inhibitory potency and specificity toward monoamine oxidase
      type-B (MAO-B). Among them, N-(2-aminoethyl)-2-chloro-4-iodobenzamide
      hydrochloride (2d) showed high inhibitory potency and selectivity against MAO-B.
      The type of MAO-B inhibition by 2d was non-competitive and the inhibition
      constant (Ki) was 0.80 microM. Strong and selective in vivo MAO-B inhibition by
      2d was also confirmed. The brain MAO-B inhibition by 2d was reversible and the
      enzyme activity completely returned to the control value 24 h after
      administration. Compound 2d was, therefore, considered to be a candidate for
      advanced development as a radioiodinated ligand that may be useful for functional
      MAO-B studies in the living brain using single photon emission computer
      tomography.

PMID- 1394695
TI  - Positron-emitting N-[18F]fluoroalkyl and [18F]fluoropyrrolidinyl analogues of
      eticlopride as potential in vivo radioligands for dopamine D2 receptors.
AB  - N-Fluoroalkyl and 4-fluoropyrrolidinyl eticlopride analogues with high affinity
      toward central nervous system dopamine D2 receptors in vitro were labelled with
      positron emitting fluorine-18 (t1/2 = 110 min), and their in vivo biodistribution
      was investigated in rats. N-[18F]Fluoro-ethyl and -propyl eticlopride derivatives
      showed poor in vivo selectivity in the rat brain. On the other hand, 4
      [18F]fluoropyrrolidinyl eticlopride exhibited almost constant and relatively high
      striatal concentration. The striatal/cerebellar radioactivity ratio, which
      corresponds to the ratio of a brain D2 receptor-rich to poor region, gradually
      increased to 5.2-6.4, 90 min after the injection. The striatal accumulation was
      selectively inhibited by pre-injection of haloperidol, a dopamine D2 antagonist,
      without affecting accumulation in other tissues. Thus, the selective striatal
      accumulation of 4-[18F]fluoropyrrolidinyl eticlopride in striatal tissue appears
      to be due to the specific binding to dopamine D2 receptors.

PMID- 1394696
TI  - Novel uracil derivatives: newly synthesized centrally acting agents.
AB  - A series of 1-amino-5-substituted uracils and their 4-thio or 2,4-dithio
      substituted analogues were synthesized and assayed for anti-conflict activity in
      rats and anesthetic activity in mice. 1-Amino-5-halogenouracils 3b-e, 1-amino-4
      thiouracil (9a), and 1-amino-5-halogeno-4-thiouracils 9c, d showed both anti
      conflict and anesthetic activities. The most active compound was 1-amino-5-chloro
      4-thiouracil (9d) which showed anxiolytic activity at 2 mg/kg of oral
      administration (p.o.) on a modified Geller-Seifter conflict schedule. Its minimum
      effective dose (MED) was lower than that of diazepam. The 50 percent effective
      dose (ED50) for anesthetic activity in mice of the compound (9d) was 32.9 mg/kg,
      p.o.

PMID- 1394697
TI  - Synthesis of trans-4-aminomethylcyclohexanecarbonyl-L- and -D-phenylalanine-4
      carboxymethylanilide and examination of their inhibitory activity against plasma
      kallikrein.
AB  - Based on studies of structure-activity relationship, trans-4
      aminomethylcyclohexanecarbonyl-L-phenylalanine-4-carbox ymethylanilide (Tra-Phe
      APAA) was designed as a selective plasma kallikrein inhibitor and synthesized.
      Tra-Phe-APAA inhibited plasma kallikrein with a Ki value of 0.81 microM, while it
      inhibited glandular kallikrein, plasmin, urokinase, factor Xa and thrombin with
      Ki values of greater than 500, 390, 200, greater than 500, and greater than 500
      microM, respectively. However, its stereoisomer, Tra-D-Phe-APPA did not exhibit
      any detectable inhibitory activity against the above enzymes.

PMID- 1394698
TI  - Synthesis and antiarrhythmic activity of 2,2-dialkyl-1'-(N-substituted
      aminoalkyl)-spiro-(chroman-4,4'-imidazolidine)-2',5'-diones.
AB  - A novel series of 2,2-dialkyl-1'-(N-substituted aminoalkyl)-spiro-[chroman-4,4' 
      imidazolidine]-2',5'-diones was synthesized and evaluated for antiarrhythmic
      activity in chloroform- or/and aconitine-induced ventricular arrhythmia in mice.
      Among these compounds, (-)-6-chloro-2,2-dimethyl-1'-[3-(4
      hydroxypiperidino)propyl] -spiro-[chroman-4,4'-imidazolidine]-2',5' -dione was
      found to be more effective than reference agents and was selected for further
      development.

PMID- 1394699
TI  - Effects of Shosaikoto (kampo medicine) on lipid metabolism in macrophages.
AB  - We investigated effects of Shosaikoto treatment on cholesterol metabolism in
      macrophages. Although macrophages, harvested from mice treated with Shosaikoto,
      took up a small amount of control low density lipoprotein (LDL) (thiobarbituric
      acid-reactive substance (TBA-RS) value was 0.27 pmol/mg of protein) as control
      macrophages, they took up more LDL modified with CuSO4 (TBA-RS value was 6.12
      pmol/mg of protein) than control macrophages. Degradation of both control LDL and
      oxidized LDL was enhanced in Shosaikoto treated macrophages. In the presence of
      control LDL or in the absence of LDL, incorporation of [3H]oleic acid into
      chlesteryl oleate was significantly reduced in Shosaikoto treated macrophages.
      This suggests that acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in
      macrophages was partly inhibited by Shosaikoto treatment. On the other hand, in
      the present of oxidized LDL, cholesteryl ester accumulated in Shosaikoto treated
      macrophages as much as in controls. However, cholesteryl oleate efflux from
      macrophages in the presence of high density lipoprotein (HDL) was enhanced in
      Shosaikoto treated macrophages. These result indicate that Shosaikoto facilitates
      oxidized LDL catabolism in macrophages, resulting in the augmentation of oxidized
      LDL uptake and the elimination of cholesterol from macrophages by HDL. These
      Shosaikoto effects may prevent foam cell formation and the progression of
      atherosclerotic lesions.

PMID- 1394700
TI  - Conjugated 1 beta-hydroxycholic acid in the urine of newborns and pregnant women
      measured by radioimmunoassay using antisera raised against N-(1 beta
      hydroxycholyl)-2-aminopropionic acid-bovine serum albumin conjugate.
AB  - Anti-tauro 1 beta-hydroxycholic acid antisera were prepared by immunizing rabbits
      with N-(1 beta,3 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholan-24-oyl)-2-
      aminopropionic acid-bovine serum albumin (BSA) conjugate. The antisera raised had
      high affinity (1.25-1.46 x 10(9) M-1) and specificity for conjugated 1 beta
      hydroxycholic acid; cross-reactivity for glyco 1 beta-hydroxycholic acid was 100%
      and that for the glycine and taurine conjugates of other 1 beta-hydroxylated bile
      acids ranged from 11.30 to 0.23%. Urinary concentrations of conjugated 1 beta
      hydroxycholic acid were determined by radioimmunoassay in newborns, 0-20 d after
      birth, in amounts ranging from 0.29 to 18.51 micrograms/ml and in women in late
      pregnancy (less than 1.13 micrograms/ml), as well as in normal women (less than
      0.12 microgram/ml).

PMID- 1394701
TI  - A radiometric assay method for aromatase activity using [1 beta-3H]16 alpha
      hydroxyandrostenedione.
AB  - [1 beta-3H]16 alpha-Hydroxyandrostenedione (16 alpha-OHA) (715 mCi/mmol) was
      prepared from commercially available [1 beta-3H]androstenedione (A) by the
      microbiological method with Streptomyces roseochromogenes and its structure and
      purity were determined by chromatographic and reverse isotope dilution methods.
      When [1 beta-3H]16 alpha-OHA was incubated with human placental microsomes and
      reduced nicotinamide adenine dinucleotide phosphate (NADPH), 3H2O-release into
      the medium was dependent upon protein concentration and incubation time. An
      apparent Km and Vmax of the microsomal aromatase for the [1 beta-3H]substrate
      were 650 nM and 34 pmol/min/mg protein, respectively. In this assay, aromatase
      activity could be determined as low as 0.1 nmol estrogen formation/min/mg
      protein. 3-Deoxyandrostenedione, a potent competitive inhibitor of the A
      aromatization, also blocked the 16 alpha-OHA aromatization in a competitive
      manner with Ki of 15 nM.

PMID- 1394702
TI  - Preparation of acetylmercapto-3-carboxypropanoyl insulins using preparative high
      performance liquid chromatography on an anion-exchange column.
AB  - A method for the preparation of insulin derivatives which have protected
      sulfhydryl group(s) at definite site(s) on the molecule is described. Porcine
      insulin reacts with S-acetylmercaptosuccinic anhydride to afford four species of
      insulin derivatives that have 2 (or 3)-acetylmercapto-3-carboxypropanoyl group(s)
      at i) Gly(A1), ii) Gly(A1) and Phe(B1), iii) Gly(A1) and Lys(B29), and iv)
      Gly(A1), Phe(B1) and Lys(B29) positions. The derivatives are efficiently
      separated in a preparative scale by anion-exchange high-performance liquid
      chromatography on a TSKgel DEAE-2SW column. The four derivatives are all readily
      deacetylated with hydroxylamine to give the corresponding sulfhydryl insulin
      derivatives.

PMID- 1394703
TI  - Catabolism of hemoglobin-haptoglobin complex in microsome subfractions.
AB  - After internalization of hemoglobin-haptoglobin complex (Hb-Hp) via receptor
      mediated endocytosis (RME) into liver parenchymal cells, organelles containing
      the complex distribute in the microsome fraction (Ms). Prior to the catabolism,
      Hb-Hp dissociates symmetrically into two 82,000-dalton (82 kDa) subunits. In the
      present investigation, the first event of Hb-Hp metabolism in Ms were further
      examined after [3H-heme, 14C-glogin]Hb-Ho or [125I-Hb]Hp injection to rats.
      Shortly after the internalization of Hb-Hp, this complex in Ms was intact. At 60
      min after injection, radioactive materials of Ms extracted by freezing and
      thawing (F&T) with yield of 15% were composed of Hb-Hp, 82 kilodaltons (kDa)
      subunits and Hb metabolites with a ratio of 1:6:13. The heme metabolites were
      identified as [3H]bilirubin by high performance liquid chromatography (HPLC). The
      ratio of Hb-Hp/82 kDa subunits/Hb metabolites in microsome residue of the F&T was
      40:8:1. The radioactivity in Ms at 60 min localized microsomes subfraction except
      Golgi light fraction. In electron microscope radioautography of microsome
      subfraction using [125I]Hb-Hp, silver grains were observed over or within
      morphologically heterogenous vesicles, e.g. vesicles containing very low density
      lipoprotein (VLDL) particles with appendage like multi-vesicular body (MVB) or
      compartment of uncoupling of receptor and ligand (CURL) in Goligi light and
      intermediate fractions. These studies suggest that Hb-Hp internalized by RME is
      dissociated symmetrically into two 82 kDa subunits in organelles of Ms, and that
      organelles with MVB or CURL-like structures are associated with Hb-Hp metabolism.

PMID- 1394704
TI  - Chromatography of beta-glucuronidase from bovine liver. A study of the enzyme
      binding sites of prepared adsorbents.
AB  - beta-Glucuronidase from bovine liver was adsorbed to the adsorbents prepared with
      CH-Sepharose 4B and either the competitive inhibitor or its analogs such as p
      aminophenyl 1-thio-beta-D-glucuronic acid, -glucoside, -galactoside, and N-acetyl
      glucosaminide. The adsorbed enzyme was eluted at 0.1 or 0.5 M NaCl by a stepwise
      gradient. Chromatography of the enzyme was also performed by using the adsorbents
      prepared with Epoxy-activated Sepharose 6B and amine compounds or other
      compounds. In order to see whether the hydroxyl groups of the sugar parts in the
      ligand are necessary for the adsorption of the enzyme, chromatography was
      performed by using the adsorbents prepared with sugar derivatives as the ligand.
      As a result, it was found that beta-glucuronidase had an affinity for adsorbents
      prepared with either acetyl derivatives or methoxy derivatives of glycosides and
      CH-Sepharose 4B. From the results of elution of the enzyme with NaCl from
      adsorbents having amide bonding, it was clarified that the affinity of the enzyme
      for adsorbents without glycosides in the ligands correlated with acidity of the
      amide in the adsorbents. Hydrogen bond chromatography was performed with the
      prepared adsorbents. The enzyme was adsorbed under a high concentration of
      ammonium sulfate, and the elution of the adsorbed enzyme from adsorbents was
      examined by the degradation of salt. The enzyme was most easily eluted from
      aminoethyl 1-thio-beta-D-glucuronic acid-CH Sepharose 4B at 0.9 M ammonium
      sulfate and at 0.5 M concentration of the salt with p-aminophenyl 1-thio-beta-D
      glucuronic acid-CH Sepharose 4B.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394706
TI  - Enzymatic synthesis of glucoside derivatives of validamine and valienamine.
AB  - alpha- And beta-glucoside derivatives of validamine and valienamine were prepared
      by enzymatic transglucosidation using alpha- and beta-glucosidase of Rhodotorula
      lactosa. The structures of these derivatives have been elucidated by 13C- and 1H
      nuclear magnetic resonance spectral analysis. Thus, 7-alpha-glucoside, 7-alpha
      isomaltoside, and 4-alpha-glucoside of validamine and 7-alpha-glucoside, 7-alpha
      isomaltoside, 4-alpha-glucoside, and 4-alpha-isomaltoside of valienamine were
      obtained from maltose and validamine or valienamine using alpha-glucosidase. 7
      beta-glucoside, 2-beta-glucoside, and 4-beta-glucoside of validamine or
      valienamine were obtained from cellobiose and validamine or valienamine using
      beta-glucosidase. These derivatives were tested for alpha-glucosidase inhibitory
      activity on rat small intestinal glycosidases.

PMID- 1394705
TI  - Effects of calphobindin II (annexin VI) on procoagulant and anticoagulant
      activities of cultured endothelial cells.
AB  - Effects of human placental calphobindin II (CPB-II) on the protein C activation
      and prothrombin activation on the cell surface of cultured calf pulmonary
      arterial endothelial cells have been investigated. CPB-II inhibited thrombin
      generation by factor Xa bound to the surface of the cultured endothelial cells in
      a dose-dependent manner. The amount (IC50) of CPB-II causing the inhibition at
      50% was estimated to be approximately 10 nM. CPB-II was found to be ineffective,
      however, in the protein C activation by thrombin-thrombomodulin (TM) complex on
      the cell surface. Assay using purified TM revealed that CPB-II was able to
      exhibit the inhibitory potency for the protein C activation exclusively in the
      reconstituted system with negatively charged phospholipids. These results suggest
      that the neutral phospholipids participate in the protein C activation through
      the thrombin-TM system on the endothelial cell surface. The ability of CPB-II to
      inhibit procoagulant activity without affecting anticoagulant activity on the
      cultured endothelial cells is probably related to its potential physiological
      function, while it is able to exert various degrees of influence upon these
      activities in blood coagulation by interacting with negatively charged
      phospholipids in vitro.

PMID- 1394707
TI  - Mechanisms of pharmacokinetic interaction between propranolol and quinidine in
      rats.
AB  - In order to study the mechanism of propranolol-quinidine interaction, the effects
      of quinidine on propranolol pharmacokinetics were examined in male Wistar rats.
      The concurrent oral administration of quinidine (10 mg/kg) markedly increased the
      plasma concentration of propranolol (2.5 mg/kg), and the area under the
      propranolol concentration-time curve increased about 3.6-fold. These results are
      consistent with previous observations in man and indicate the possible usefulness
      of the male Wistar rat as an animal model for investigating the mechanisms of the
      drug interaction. When propranolol was given intravenously, a concurrent
      administration of quinidine increased the apparent distribution volume of
      propranolol, mainly by decreasing its plasma protein binding. However, the
      systemic clearance of propranolol was not significantly altered by quinidine.
      Thus, quinidine increased the availability of oral propranolol from 13.8 +/- 2.2
      to 44.2 +/- 4.6% (p less than 0.01). Furthermore, quinidine delayed the
      elimination of propranolol from the isolated perfused rat liver. These results
      indicate that quinidine reduces the presystemic elimination of propranolol in the
      liver, thereby increasing its systemic availability after oral administration.

PMID- 1394708
TI  - Increase in water permeability of negatively charged liposomal membrane by local
      anesthetics.
AB  - Effect of the local anesthetics dibucaine, tetracaine, lidocaine and procaine on
      the water permeability of phospholipid membrane was examined using liposomes
      composed of bovine heart cardiolipin and egg yolk phosphatidylcholine in a molar
      ratio of 2/98 by monitoring the osmotic shrinkage of liposomes in hypertonic
      glucose solution at pH 7.3 and 30 degrees C. These local anesthetics greatly
      accelerated the water permeability by destabilizing the membrane structure. The
      effect was found to be governed by the hydrophobicity of the anesthetics. There
      was also a significant correlation between the membrane destabilizing actions and
      the anesthetic activities.

PMID- 1394709
TI  - Bioavailability of morphine in rabbits after rectal administration of suppository
      containing controlled release morphine tablet.
AB  - Two kinds of sustained release morphine suppositories have been prepared; one is
      an oleaginous base suppository (MSC) containing a controlled release morphine
      tablet (MST: MS Contin), and the other is a hollow-type suppository (MSCH)
      containing MST and morphine powder packed in its hollow space. In vitro release
      tests and in vivo rectal absorption experiments in rabbits were performed. The
      profiles of morphine release from MST and MSC in vitro were similar, and revealed
      that suppository bases had no effect on the release profile of morphine from the
      preparation. Morphine release from MSCH was rapid in the early phase, and then
      enclosed morphine was slowly and continuously released from MST. Phamacokinetics
      of morphine from the suppository were compared with the orally administered MST,
      and it was found that there was no difference in the maximum plasma concentration
      (Cmax) and the peak time (Tmax) between MSC and MST, but the mean residence time
      (MRT) of MSC was approximately three times longer than that of MST, and the
      extent of bioavailability (BA) of MSC was significantly larger than that of MST
      (71.6 +/- 14.2% and 11.9 +/- 4.0%, respectively). Cmax can be altered arbitrarily
      by changing the morphine content in the hollow space of MSCH. As in the case of
      MSC, the plasma concentration of morphine from MSCH was maintained. It is
      concluded from the above results that MSC is a satisfactory sustained release
      morphine suppository for the treatment of cancer pain, administering it twice a
      day, and that MSCH is effective due to its fast analgesic effect and sustained
      release nature not only for cancer pain but also for surgical operations.

PMID- 1394711
TI  - Assay of cell surface-bound immunoliposomes using monoclonal antibody reactive
      with a cross-linking reagent.
AB  - A monoclonal antibody (mAb) reactive with a crosslinking reagent, N-(m
      maleimidobenzoyl)dipalmitoylphosphatidylethanolamine (mMBPE), in liposomes was
      produced from a hybridoma clone established by a fusion between P3X63Ag8.653
      mouse myeloma cells and spleen cells from a BALB/c mouse hyperimmunized with the
      antibody-coated liposomes containing mMBPE. Using this mAb (termed AL-6), the
      quantity of immunoliposomes bound on target tumor cells was assessed by flow
      cytofluorometry. The results obtained using fluorescein isothiocyanate-coupled AL
      6 allowed the enumeration not only of the immunoliposomes bound on all tumor
      cells but also those on individual target tumor cells. The relevance of this
      assay method was confirmed by a comparison with another assay method of cell
      bound liposomes using immunoliposomes containing carboxyfluorescein in the
      vesicles.

PMID- 1394710
TI  - Effects of fatty acids, fatty amines and propylene glycol on rat stratum corneum
      lipids and proteins in vitro measured by fourier transform infrared/attenuated
      total reflection (FT-IR/ATR) spectroscopy.
AB  - Fourier transform infrared/attenuated total reflection (FT-IR/ATR) spectroscopy
      was used to examine the effect of fatty acids, fatty amines and propylene glycol
      (PG) on the molecular mobility of rat stratum corneum lipids and keratinized
      proteins, using a hydrophobic solute, indomethacin, and a polar solute, 5- and 6
      carboxyfluorescein (CF). Treatment of the skin with either oleic acid or
      oleylamine resulted in significant CH2 C-H asymmetric stretching band shifts and
      broadening. The extent of spectral alteration varied with the chemical structure
      of the penetrant. The penetrants increased the lipophilic indomethacin flux and
      shortened the lag times through the skin in vitro. The plot of frequency changes
      vs. indomethacin flux or lag time demonstrated a linear relationship, thus
      indicating that spectral alteration in CH2 C-H stretching regions of stratum
      corneum lipids may provide a reliable index for characterizing penetrants. The
      data also showed that the hydrophilic group which attached to the CH2 group in
      the penetrant molecules did not play a part in the membrane permeability
      enhancing action. Oleic acid and oleylamine appeared to induce a conformational
      alteration of the keratinized proteins from alpha-helix to beta sheet. Such
      alteration was also observed with PG treatment. Accumulation of CF was
      significantly increased by the PG pretreatment of the skin, thus suggesting that
      PG-induced protein conformational changes could be related to the enhancement of
      CF accumulation.

PMID- 1394712
TI  - Evaluation of enteric coated tablet sensitive to pancreatic lipase. I. In vitro
      disintegration test.
AB  - We designed a new enteric coated preparation which is pH independent and
      functions by pancreatic lipase activity in the duodenum. Triolein (TO) and
      trilaurin (TL) were selected as lipase sensitive components and ethylcellulose
      (EC) was used as the support film for TO and TL. Tablets (330 mg, d = 10 mm)
      containing a model drug, sulfamethizole (SMZ), were coated with 1% each of TO, TL
      and EC solution by the fluidized bed coating technique. Disintegration tests were
      carried out in the media including JPXI 1st fluid (pH 1.2, JP-1), 2nd fluid (pH
      6.8, JP-2) and JP-2 with gall powder and pancreatic lipase (JP-2-GL). The lag
      time of disintegration of the tablet (TOTL-Tab) coated 5-7 mg/tab with TO, TL and
      EC was about 10 min and all of the tablets disintegrated completely within 30 min
      in JP-2-GL. However, in the other media, which did not contain lipase, TOTL-Tab
      did not disintegrate for at least 2 h. It was confirmed that TO and TL in the
      coating film were digested by lipase. In addition, the tensil strength of the
      film decreased quickly after incubation in JP-2-GL. These results suggest that
      the application of TO, TL and EC to tablet coating is useful for an enteric
      release preparation sensitive to pancreatic lipase, even if patients have low
      gastric acidity or are taking antacids.

PMID- 1394713
TI  - Percutaneous absorption of ketoprofen from acrylic gel patches containing d
      limonene and ethanol as absorption enhancers.
AB  - The percutaneous absorption of ketoprofen (KPF) from gel patches containing d
      limonene and ethanol was investigated in rats. Plasma levels of KPF varied with
      the kind of polymers which constitute the gel patch, and the highest level was
      observed when the copolymer of ethylacrylate (EA) and
      diethyleneglycolmethacrylate (DEGMA) was used as a vehicle. The amount of KPF
      permeating through the rat skin from the gel patch was well correlated with that
      of ethanol. Permeations were enhanced with increase in the amount of d-limonene
      distributed from the vehicle to the skin tissue. The amount of d-limonene
      accumulated in the skin varied greatly with the kind of polymers; the highest
      accumulation was observed with the EA-DEGMA copolymer, and decreased with
      increasing affinity of d-limonene to the polymers. The reason EA-DEGMA copolymer
      showed the highest percutaneous absorption of KPF from gel patches containing d
      limonene may be the hydrophilic nature of this polymer which showed the lowest
      affinity to d-limonene.

PMID- 1394714
TI  - Dose-dependent pharmacokinetics of glycyrrhizin in rats.
AB  - The dose-dependent pharmacokinetics of glycyrrhizin (GLZ) was investigated by
      measuring drug disappearance from plasma and biliary excretion in rats. The
      decline in plasma concentration was biexponential after an i.v. dose of 5, 10,
      20, or 50 mg/kg. Dosage, however, had a marked effect on the pharmacokinetics,
      with a greater-than-proportional increase in area under the plasma concentration
      curve (AUC) at doses of 20 and 50 mg/kg, even though the increase was
      proportional at doses of 5 and 10 mg/kg. There was also a significant increase of
      the steady-state distribution volume (Vdss), as well as significant decreases in
      total body (CLtot) and biliary (CLB) clearances, at 20 and 50 mg/kg from those at
      5-10 and 5-20 mg/kg, respectively. The AUC, Vdss, and renal clearance (CLR) at a
      given dose showed no significant difference between rats with and without bile
      fistulas. The plasma unbound fraction (fp) (0.006-0.026) increased with
      increasing plasma GLZ concentration over the observed range (2-900
      micrograms/ml). No significant change in Vdss for unbound GLZ was observed
      between the doses, indicating that the distribution of GLZ into tissues is not
      changed by an increase in dose. On the other hand, a dose dependency in CLtot for
      unbound GLZ was observed and confirmed to be attributed to dose dependency in CLB
      for unbound GLZ since there was no significant difference in CLR or metabolic
      clearance for unbound GLZ between the doses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394715
TI  - Studies on natural antioxidants in citrus species. I. Determination of
      antioxidative activities of citrus fruits.
AB  - The antioxidative activities of twenty types of citrus fruits were investigated
      with a screening method which is based on rat liver microsomal lipid peroxidation
      induced by dihydronicotinamide adenine dinucleotide phosphate (NADPH) and
      adenosine diphosphate (ADP). The activities of the exocarp were greater than
      those of the sarcocarp and the activities from immature fruits (collected in July
      August) were greater than those from mature fruits. The strongest antioxidative
      activity was found in ponkan (Citrus reticulata Blanco) collected in July.

PMID- 1394716
TI  - Direct injection method for quantitation of delta-aminolevulinic acid in urine by
      high-performance liquid chromatography.
AB  - A highly sensitive and simple method for determining delta-aminolevulinic acid
      (ALA) in urine was established, using direct injection of urine into a high
      performance liquid chromatographic column, with fluorometric detection after post
      column derivatization with o-phthalaldehyde (OPA). The recovery of ALA was about
      100% and ALA was completely separated on an ion exchange column (retention time,
      38 min). The detection limit for ALA was 10 pmol (S/N = 2). The mean levels of
      urinary ALA of 10 healthy volunteers, 4 patients with acute intermittent
      porphyria, and 2 workers occupationally exposed to lead were 0.76, 5.25, and
      23.54 mg/l, respectively. Because of its simplicity, the method is considered to
      be suitable for routine analysis of urinary ALA in the clinical laboratory.

PMID- 1394717
TI  - Enzyme linked immunosorbent assay for beta-endorphin in human plasma.
AB  - We established a highly sensitive and specific double-antibody enzyme linked
      immunosorbent assay for beta-endorphin (beta-EP). For competitive reactions, the
      beta-EP-antibody was incubated with beta-EP standard (or sample) and beta-D
      galactosidase-labeled beta-EP (delayed addition). Free and antibody-bound labeled
      antigen were separated by using an anti-rabbit immunoglobulin G coated
      immunoplate. The enzyme activity on the plate was fluorometrically determined.
      The minimal detection limit was approximately 0.4fmol/well (10 pmol/l). Using
      this assay system, beta-EP-like immunoreactivity (-LI) in human plasma was
      determined. The level of beta-EP-LI in extracted human plasma from 6 normal
      subjects was 2.44 +/- 0.68 pmol/l. High performance liquid chromatography
      analysis of the plasma of a normal subject revealed a single immunoreactive form
      which eluted with the same retention time as that of synthetic beta-EP.

PMID- 1394718
TI  - Antitumor activity of Hypsizigus marmoreus. I. Antitumor activity of extracts and
      polysaccharides.
AB  - Antitumor activity of Hypsizigus marmoreus, one of the most popular Japanese
      edible mushrooms, was investigated. The aqueous and methanol extracts were tested
      against allogeneic tumor, solid sarcoma 180 and syngeneic tumor, Meth A
      fibrosarcoma. The aqueous extract was highly active in inhibiting growth of solid
      sarcoma 180, but not as much for Meth A fibrosarcoma. Fractionation of antitumor
      substances of the aqueous extract isolated four polysaccharides. Chemical
      analysis revealed one of them to be beta-(1-3)-glucan with a remarkable
      inhibitory effect against tumor-growth of sarcoma 180.

PMID- 1394719
TI  - Dose-dependent enzyme suppression in spleen induced by GM1 (monosialoganglioside
      1) administration to mice.
AB  - Our previous studies suggested that the administration of exogenous gangliosides
      to the body modulates enzymatic networks in the brain. In the present study, we
      tested whether that is the case with another organ, spleen. By testing the dose
      response relationship, we found that there is a optimum dose for the effect of
      enzymatic modulation of GM1 (monosialoganglioside 1) administration. Although the
      optimum level varied depending on each of the examined hydrolytic enzymes, it
      usually fell in the range around 50 micrograms/kg body weight. The findings led
      us to conclude that the enzyme-modulating actions of gangliosides come not merely
      from the bizarre actions in vivo of high molecular exogenous substances.

PMID- 1394720
TI  - Preparations of cyclic sulfoxide derivatives and their evaluation as transdermal
      penetration enhancers.
AB  - Novel cyclic sulfoxides, such as 2-octyl, 2-dodecyl and 2
      hexadecyltetrahydrothiophene-1-oxide were prepared by the alkylation of
      tetrahydrothiophene-1-oxide. Additionally, 2-methyl, 2-ethyl and 2-propyl-5
      dodecyltetrahydro-thiophene-1-oxide were conducted by further alkylation. Their
      enhancing activity on the penetration of indomethacin through rabbit skin was
      evaluated in in vitro experiments, and the effect of the alkyl length on the
      enhancing activity was discussed. Among the 2-alkyl-tetrahydrothiophene-1-oxides,
      the compounds containing dodecyl and hexadecyl groups promoted a much greater
      penetration of the drug through the skin than the compound containing an octyl
      group. A stronger effect was observed in the experiment using 2-dodecyl-5
      alkyltetrahydrothiophene-1-oxide, as compared with the that of 2-dodecyl
      tetrahydrothiophene-1-oxide. The substitution of the alkyl groups to the next
      position of the sulfoxide group seemed to make the enhancing activities large.

PMID- 1394721
TI  - Species and organ differences of sulphate conjugation of p-nitrophenol in liver
      and platelets.
AB  - Sulphate conjugation of p-nitrophenol (p-NP) in the liver and platelet cytosol of
      guinea pigs, rabbits and dogs were studied. The dependency of phenol
      sulphotransferase (PST) activity on p-NP concentration in the liver of guinea
      pigs and rabbits and in the platelets of guinea pigs were similar to that
      reported for the liver (Mizuma et al., J. Pharmacobio-Dyn., 6, 851 (1983)) and
      platelets (Nakamura et al., J. Pharm. Pharmacol., 42, 207 (1990)) of rats. There
      was one peak of PST activity on p-NP at the concentration of 1 to 10 microM, and
      the PST activity was increased again with an increase of p-NP concentration above
      the original concentration. On the other hand, a peak in PST activity on p-NP at
      the concentration of 1 to 10 microM was not observed in the platelets of rabbits
      and dogs. These results indicated species and organ differences in PST activity
      on p-NP in liver and platelets. The biphasic activities of the PST and p-NP in
      platelets and liver of rat and guinea pig were similar to that reported in humans
      (Reiter et al., Naunyn-Schmiedeberg's Arch. Pharmacol., 324, 140 (1983)).

PMID- 1394722
TI  - [Classification and analysis of social-psychologic nursing diagnosis from 86
      inpatients suffering from malignant tumors].

PMID- 1394723
TI  - [Experience in the nursing management of the model wards in the medical centres].

PMID- 1394724
TI  - [Nursing care of transcatheter radio frequency, ablation in patients with Wolff
      Parkinson-White syndrome].

PMID- 1394725
TI  - [Nursing care of tricuspid atresia children after improvised Foutan surgery].

PMID- 1394726
TI  - [Advances in nursing care in communicable diseases].

PMID- 1394727
TI  - [Our multi-levels of continuing education in nursing].

PMID- 1394728
TI  - [Clinical studies of psychotropic drugs in pediatric patients].

PMID- 1394729
TI  - [Peri-operative care of pheochromocytoma surgery].

PMID- 1394730
TI  - [Postoperative care of tension band internal fixation].

PMID- 1394732
TI  - [Normal radiographic appearance of the distal ends of the radius and ulna--a
      correlative radiographic and histologic slab study of the wrists in 50 infants].
AB  - Based on a correlative radiographic and histologic slab study of the wrists in 50
      infants who died of unrelated diseases, the author's chief conclusions are as
      follow: 1) On the wrist radiograph of the infant, bone bark in the Ranvier's
      groove may appear as a "thorn-like" bony process on the margins of the metaphysis
      of the radius and ulna. 2) The radiographic appearance of the provisional zone of
      calcification at the distal ends of the radius and ulna are variable on
      radiographs of normal wrists, and familiarity with these variations precludes
      incorrect diagnosis. 3) The locations of the partially convex part of the
      provisional zone of calcification on the radiograph of the wrist correspond to
      where the vessels in the epiphyseal cartilage are located.

PMID- 1394731
TI  - [Relationship between various stromal cells in long-term bone marrow culture].
AB  - In the present studies, the relationship and special junctions between various
      stromal cells in long term bone marrow culture were reported. The possible
      significance of these signs vis-a-vis the hemopoietic microenvironment were
      discussed. Fibronectin and thrombospondin were detected on the substratum and
      surface of the stromal cells using immunogold techniques. These adhesion proteins
      on the stromal cells might be important in cell-cell and cell-stroma connection.

PMID- 1394733
TI  - [A study on the role of immunosuppression in the pathogenesis of brucellosis].
AB  - An immunosuppressive effect was seen in murine brucellosis as detected by using
      plaque forming cell (PFC) and 3H-labelled lymphocyte blastogenesis transformation
      (LBT) assays. The immunosuppression PFC could last until 11 months after
      infection, while that of LBT was only seen at 3 months after infection. This
      immunosuppression could be relieved by using immunomodulators such as levamisole,
      bestatin, IL-2 and polyporus umbellatus. IL-2 and polyporus umbellatus could
      reverse the suppression to normal levels. Thus, this study provided evidence that
      immunosuppression is a component of pathogenesis of brucellosis.

PMID- 1394734
TI  - [Synthesis and cloning of the whole human erythropoietin (EPO) gene].
AB  - A 600 bp synthetic erythropoietin (EPO) gene encoding all 166 amino acids of the
      EPO protein and 27 amino acids of the signal peptide has been constructed. The
      whole gene was divided into three large fragments consisting of a total of 32
      oligonucleotides. These oligonucleotides were synthesized by the solid-phase
      phosphor-amidite method and ligated into three large fragments. These latter
      three were separately cloned into vector M13mp19 and then transformed into E.
      coli JM 103. Positive clones were screened with 32P-labeled probes. The sequences
      of the fragments were confirmed by DNA sequencing, and the sequence of the whole
      synthetic EPO gene was confirmed by enzymatic digestion and sequencing. The
      results indicated that the nucleotide sequence of the synthetic EPO gene is
      identical to that of the original.

PMID- 1394735
TI  - [Specific killing of human leukemic T-cells by a monoclonal antibody coupled to
      the cytotoxin from Chinese cobra].
AB  - The immunotoxin (IT) was prepared by conjugating cytotoxin from Chinese Cobra
      (Naja naja Atra) venom with monoclonal antibody (McAb) Wu71 directed to human T
      cells. First, calcium ions were used to suppress the cytolytic reaction while
      cell antigen was allowed to react with McAb. Then magnesium ions and the
      chelating agent EGTA were used to abolish the calcium inhibition. With this
      treatment, the IT showed high cytotoxicity for the leukemic cell line CEM, which
      was antigen positive (82.4% of the cells were killed at a concentration of 0.5 x
      10(-6) mol/L of IT), but very little cytotoxicity for the antigen negative cell
      line Raji (23.3% cells were killed at the same concentration). Under scanning
      electron microscopy, it could be seen that the cell membranes of CEM were broken
      by IT, and the cells had died. The results suggest that the McAb Wu71 plus
      cytotoxin IT has potential application in leukemia therapy.

PMID- 1394736
TI  - [Risk factors analysis of leukemia and aplastic anemia in China. Chinese
      Epidemiologic Study Group of Leukemia and Aplastic Anemia].
AB  - Based on the incidence survey of leukemia and aplastic anemia (AA) from 1986 to
      1988, Case control studies (1257 new leukemia cases and 339 new AA cases) were
      carried out according to the type of leukemia and AA in order to better
      understand the epidemiologic characteristics of the diseases. Controls were
      matched randomly (age, sex and ethnic group) from the same population. The data
      were analyzed with the conditional Logistic multi-regression model and calculated
      on an IBM-PC/XT. The risk factors of M2a were found to be X-rays, antipyretics,
      benzene, pesticides and bimolane; that of M3 was chloramphenicol; that of M5 was
      X-rays; and that of other ANLLs was phenylbutazone. The risk factors of ALL were
      chloramphenicol, phenylbutazone and family members with cancer; those of CML were
      X-rays and hepatitis; those of CLL were chloramphenicol and benzene; those of AAA
      were antipyretics and hepatitis; and that of CAA ws X-rays.

PMID- 1394737
TI  - [Pulmonary impedance plethysmographic features of obliterative pulmonary
      hypertension].
AB  - Pulmonary impedance plethysmography (PIP) has been used for the diagnosis of cor
      pulmonale secondary to COPD for about ten years. But the PIP features of
      obliterative pulmonary hypertension (OPH) have not yet been reported. We carried
      out a comparative study between PIP and hemodynamics determined by
      catheterization, in which 32 cases of OPH were studied. The results showed that
      the PIP features of OPH included a delayed delta Zmax peak, and the QZM interval
      had a positive linear correlation with pulmonary arterial pressure (r = 0.67, P
      less than 0.0001). According to electric field theory, it was supposed that this
      phenomenon might be due to narrowed pulmonary arterioles which limit the blood
      flow.

PMID- 1394738
TI  - [Effect of d-catechin on carbon tetrachloride- and d-galactosamine-induced
      cytotoxicity in primary cultured rat hepatocytes].
AB  - The effects of d-catechin (d-CTC) on carbon tetrachloride- and d-galactosamine (d
      Ga1N)-induced cytotoxicity in primary cultured rat hepatocytes were examined.
      After 1.5 h preincubation, d-CTC was added at doses of 0.1-5.0 mg/ml to culture
      medium together with 10 mmol/L CCl4 or 5 mmol/L d-GalN, respectively. GOT, GPT
      and LDH levels were measured 1.5 h after treatment. The results showed that d-CTC
      at doses of 0.6 to 5.0 mg/ml could protect the hepatocytes against the toxic
      effects of CCl4 and d-GalN. At the higher doses (2.5-5.0 mg/ml), d-CTC showed
      weak inhibition of LDH and GPT activities, but these did not influence its anti
      hepatotoxic activity.

PMID- 1394739
TI  - [Acute effect of small dosages of somatostatin analogue SMS201-995 on gallbladder
      contractility in normal adults].
AB  - Recently, a long-acting, somatostatin analogue, SMS201-995(SMS), has been
      developed and extensively investigated. It has been proved to be remarkably
      effective in treating many diseases, including active acromegaly. We observed the
      effect of SMS on gallbladder contractility in normal adults using the fatty meal
      test. Our results show that gallbladder contractility was inhibited significantly
      for 6 hours after the subcutaneous injection of SMS in dosages of 50, 25, 12.5,
      and 5 micrograms. We conclude that it is not practical to avoid gallbladder
      disfunction during long-term SMS treatment by decreasing the dosages of SMS.

PMID- 1394740
TI  - [YAG laser treatment in anterior segment disease of the eye].
AB  - Three hundred and fifty-two eyes (230 patients) with various diseases were
      treated with the first China-made YAG laser therapy instruments. The success rate
      was 100%. Two hundred and seventy-six eyes with primary angle closed glaucoma
      were treated by peripheral iridotomy. Postoperatively, the IOP was lowered by
      0.267 kPa (2.43 mmHg). The dose and frequency of medication could then be
      lowered. The closed chamber angle index improved. Forty-nine eyes with membranous
      cataract were treated by posterior capsulotomy: Visual acuity was improved by
      95%. The main complications during or immediately after operation were as
      follows: transient elevation of IOP, hyphema, anterior uveitis and corneal edema.
      All of these were well controlled.

PMID- 1394741
TI  - [Preparation of liposomes entrapping plasmid DNA and linear DNA].
AB  - Liposomes entrapping plasmids pSV2-neo DNA, pUC18-ras DNA, pSV2-neo-ras DNA and
      linear DNA were prepared. The liposomes were composed of DOPC/Chol/OA (4:4:3) and
      pH-sensitive DOPE/Chol/OA (4:4:3), respectively. The efficiency of DNA entrapment
      was about 50%. Gel electrophoresis analysis showed: Liposome-entrapped DNA was
      not digested by DNase; The entrapped DNA molecules were intact and stable for at
      least 5-6 months at 4 degrees C. During preparation of pH-sensitive liposome, the
      pH must be kept at 8.0.

PMID- 1394742
TI  - [Primary culture of rat pituitary cells in serum-free medium].
AB  - A method for primary culturing of rat anterior and intermediate/posterior
      pituitary cells in complete serum-free defined medium (CSFM) is described.
      Dispersed pituitary cells were prepared by using a multiple enzyme digestion
      system. Insulin, transferrin and serum albumin were essential additives for
      maintenance of primary rat pituitary cells in CSFM. Morphological
      immunocytochemical and RIA studies during three weeks' culture indicated that
      beta-endorphin-like immunoreactivity (beta-End-IR) was contained in and released
      from pituitary cells. The secretion rate remained almost constant for 2 weeks
      after the 5th day in culture. This method provides an ideal in vitro model for
      studying the effects of various factors on the synthesis and release of beta
      endorphin in pituitary cells and the mechanism of regulation of other target
      gland hormones.

PMID- 1394743
TI  - [Ageing suppresses the enhancement of T cell mitogenesis by opioid peptides and
      enkephalins increase phagocytosis of murines macrophage].
AB  - The opioid peptides methionine enkephalin (M-ENK) and beta-endorphin (beta-END)
      (1 x 10(-5)-1 x 10(-11) mg/ml) were investigated for their effect on the PHA
      (1:500, 1:750 or 1:1000) induced proliferative response of old and young Wistar
      rat splenic lymphocytes in vitro. The different effects in young and old rats on
      proliferative response to PHA were determined. The results showed that MENK and
      beta-END significantly enhanced the proliferative response to PHA in young rats,
      while enhancement by M-ENK and beta-endorphin (PHA 1:750, 1:1000) was not
      observed in old rats. The PHA-induced proliferative response was 30%-40% lower in
      old rats than in young rats. Our results suggest an altered response to neuro
      immunomodulation with age. The in vitro effect of ENKs on phagocytosis was also
      studied. The results indicated that LENK (10(-4)-10(-6) mg/ml) and MENK (10(-2)
      10(-4) mg/ml) could stimulate the phagocytosis of peritoneal macrophages from
      Balb/c mice.

PMID- 1394744
TI  - [Clinical and instrumental evaluation of erectile impotence: a proposal of a
      diagnostic protocol].
AB  - There has been increasing interest in recent years in patients complaining of
      erectile dysfunction. This has prompted research and the development of
      diagnostic procedures aimed at allowing increasingly rapid characterization of
      the type of impotence involved (psychogenic or organic) and thus the most
      effective treatment. In this preliminary study, we present our study methodology
      in patients with erectile dysfunction, emphasising in particular the diagnostic
      procedures best suited to revealing the presence of an organic cause in the
      pathogenesis of impotence.

PMID- 1394745
TI  - [Surgical treatment of common bile duct calculosis: a comparative critical
      evaluation of long-term results of sphincterotomy and choledochotomy approaches].
AB  - From an analysis of operations performed by the Authors between 1974 and 1988,
      sphincterotomy emerged as the operation of choice given the small percentage of
      complications compared to the higher percentage of complications that arose with
      choledochotomy with external biliary derivation, in which use of the Kehr tube is
      hardly ever directly implicated. However the results of choledochotomy shown also
      demonstrate a possible improvement through better intraoperative procedures or by
      complementary endoscopic sphincterotomy where indicated; hence this procedure
      with external biliary deviation, according to the Authors, merits reevaluation.

PMID- 1394746
TI  - [Biomechanical and clinical interpretation of firearm wounds. General problems.
      V. The propaedeutic ABC of terminal ballistics].
AB  - Modern portable firearms, whether for military or civilian use, present
      substantially different features as instruments for striking, wounding and
      killing compared to those used in the past on account both of their intrinsic
      characteristics as thermo-chemico-ballistic machines, guaranteeing extra, more
      easily achievable performance and of the characteristics of the bullets used. The
      factors responsible for this difference, which consists essentially in an
      unprecedented wounding capability, are, in the military field, the enormous
      amount of research which only now is beginning to yield a bare minimum of
      concrete results in terms of futuristic forms and devastating performance,
      amongst other things because it is easier to achieve, and, in the "civilian"
      field, the maniacal search for an unlikely definitive wound, based on the unusual
      nature of the cartridge and on sophisticated training.

PMID- 1394747
TI  - [A rare cause of intestinal occlusion: Morgagni-Larrey hernia].
AB  - Authors report a case of Morgagni-Larrey obstructed hernia recently observed.
      After remembering pathogenetic hypothesis and pathological findings, they discuss
      clinical patterns, diagnostic tools and differential diagnosis. Authors suggest
      to consider surgical repair as a choice treatment, also for asymptomatic
      patients.

PMID- 1394748
TI  - [Rupture of the cervical esophagus. Apropos of a case of perforation by a foreign
      body].
AB  - The Authors describe a case of perforation of the cervical oesophagus by a
      foreign body (dental prosthesis). After outlining the clinical and instrumental
      elements which may be useful in the diagnosis, the Authors go on to tackle the
      topic of the most appropriate choice of therapy in the course of foreign-body
      perforation and in perforation of the oesophagus in general.

PMID- 1394749
TI  - Continuing medical education is as important as patient care.

PMID- 1394750
TI  - Postoperative analgesia in the paediatric patient.

PMID- 1394751
TI  - The continuing medical education needs of anaesthetists.
AB  - Learning needs assessment is the term applied to the process of identifying or
      diagnosing a learner's educational needs. It is the foundation of a systematic
      continuing medical education (CME) programme. Needs assessment has been
      identified as the most pressing problem of medical education directors in North
      America. Furthermore, the CME learning needs, interests or motivations of
      anaesthetists have never been studied. The amount of time and effort required for
      needs assessment is probably a major deterrent to this activity. The
      investigators adopted simple and straightforward means of assessing the
      "perceived learning needs" and topic interests of anaesthetists. Questionnaires
      were sent by mail to anaesthetists practicing in teaching and non-teaching
      hospitals in the Toronto area. The questionnaire presented a list of CME content
      areas. The respondents were asked to indicate on scale of 1 to 10 their Current
      Expertise, Ideal-Desired Expertise, and Interest-Motivation levels for each
      content area. Need Score for each content area was calculated by taking the
      difference between Ideal and Current Expertise responses. A total of 101/305
      anaesthetists (29%) responded to the survey. Most of the respondents had been in
      anaesthesia practice for less than ten years. Regional nerve block, acute pain
      control, and medicolegal considerations received high overall ranks in both the
      need and interest categories. Paediatric anaesthesia, anaesthesia for trauma
      surgery and thoracic anaesthesia had top ranks among the subspecialty fields.
      Regional anaesthesia techniques received higher need and interest ranks than
      intravenous and inhalational techniques. The learning needs of anaesthetists of a
      large urban centre have been identified, and this information is useful to CME
      planners.

PMID- 1394753
TI  - Analgesic efficacy and safety of a caudal bupivacaine-fentanyl mixture in
      children.
AB  - The analgesic efficacy and safety of a single caudal injection of a bupivacaine
      fentanyl mixture was investigated in this prospective, controlled, triple-blinded
      study of 34 children, aged 1-11 yr and of ASA physical status I-II undergoing
      urological surgery. After induction of anaesthesia and before surgery, the
      children were randomly assigned to receive a caudal injection of 1.0 ml.kg-1
      bupivacaine 0.125% with epinephrine 1:400,000 and either fentanyl 1.0
      microgram.kg-1 in 1.0 ml of normal saline or 1.0 ml of normal saline. After
      completion of surgery, patients were assessed in the recovery room for six hours
      from the time of the caudal injection and for a further 18 hr on the ward. While
      in the recovery room arterial oxygen saturation and respiratory rate were
      monitored continuously and recorded hourly together with end-tidal carbon
      dioxide, pain and sedation scores. Other complications were also recorded. While
      on the ward, pain and sedation scores, respiratory rate and side effects were
      recorded every two hours. Postoperative analgesia was provided by intravenous
      morphine. Analgesic requirements were recorded for the 24-hr study period. Pain
      and sedation scores did not differ between groups. Respiratory depression or
      hypoxia did not occur. The incidences of other side effects did not differ. There
      were no differences in the numbers of patients requiring morphine within eight
      hours, the time to first morphine administration or the total morphine
      requirements. We conclude that a single caudal injection of a bupivacaine
      fentanyl mixture with epinephrine administered prior to surgery, while safe,
      offers no advantage over an injection of bupivacaine 0.125% with epinephrine for
      paediatric urological surgery.

PMID- 1394752
TI  - Perioperative effects of oral ketorolac and acetaminophen in children undergoing
      bilateral myringotomy.
AB  - Prophylactic administration of analgesics before surgery can decrease the
      intraoperative anaesthetic requirement and decrease pain during the early
      postoperative period. In a double-blind, placebo-controlled study involving 90
      healthy ASA physical status I or II children undergoing bilateral myringotomy, we
      compared the postoperative analgesic effects of oral acetaminophen and ketorolac,
      when administered 30 min before induction of anaesthesia. Patients were
      randomized to receive saline (0.1 ml.kg-1), acetaminophen (10 mg.kg-1) or
      ketorolac (1 mg.kg-1) diluted in cherry syrup to a total volume of 5 ml.
      Anaesthesia was induced and maintained with halothane and nitrous oxide via a
      face mask. Postoperative pain was assessed by a blinded observer using an
      objective pain scale. The three study groups were similar with respect to
      demographic data, duration of anaesthesia and surgery, induction behaviour,
      oxygen saturation, incidence of postoperative emesis and, recovery times. The
      ketorolac group had lower postoperative pain scores and required less frequent
      analgesic therapy in the early postoperative period compared with the
      acetaminophen and placebo groups. In contrast, there were no differences in pain
      scores or analgesic requirements between the acetaminophen and the placebo
      groups. We conclude that the preoperative administration of oral ketorolac, but
      not acetaminophen, provided better postoperative pain control than placebo in
      children undergoing bilateral myringotomy.

PMID- 1394754
TI  - Rocuronium (ORG 9426) neuromuscular blockade at the adductor muscles of the
      larynx and adductor pollicis in humans.
AB  - The effects of rocuronium, 0.25 or 0.5 mg.kg-1, were measured simultaneously on
      the adductor muscles of the larynx and adductor pollicis in 14 adult patients.
      Anaesthesia was induced and maintained with propofol and fentanyl. Tracheal
      intubation was performed without muscle relaxants. The recurrent laryngeal and
      ulnar nerves were both stimulated supramaximally, at the notch of the thyroid
      cartilage and at the wrist respectively, using train-of-four stimulation. The
      laryngeal response was evaluated by measuring the pressure change in the cuff of
      a tracheal tube positioned between the vocal cords. Onset time, intensity of
      blockade and duration of action were less at the larynx than at the adductor
      pollicis. After rocuronium, 0.25 mg.kg-1, the onset time (interval between
      injection and maximal T1 blockade) was 1.6 +/- 0.1 min and 3.0 +/- 0.3 min (mean
      +/- SEM) at the laryngeal muscles and adductor pollicis, respectively (P less
      than 0.01 between muscles). Maximum blockade was 37 +/- 8% and 69 +/- 8%,
      respectively (P less than 0.05), and time to 90% T1 recovery was 7 +/- 1 min and
      20 +/- 4 min, respectively (P less than 0.05). With 0.5 mg.kg-1, the onset time
      was also more rapid at the vocal cords (1.4 +/- 0.1 min) than at the adductor
      pollicis (2.4 +/- 0.2 min, P less than 0.001). Maximum blockade was 77 +/- 5% and
      98 +/- 1%, respectively (P less than 0.01), and time to 90% T1 recovery was 22 +/
      3 min and 37 +/- 4 min, respectively (P less than 0.01).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1394755
TI  - Carbon dioxide absorption and gas exchange during pelvic laparoscopy.
AB  - Twelve ASA physical status I-II patients undergoing pelvic laparoscopy for
      infertility were enrolled in a study to quantify the effects of CO2 insufflation
      and the Trendelenburg position on CO2 elimination and pulmonary gas exchange, and
      to determine the minute ventilation required to maintain normocapnia during CO2
      insufflation. Measurements of O2 uptake (VO2), CO2 elimination (VCO2), minute
      ventilation (VE), FIO2, and respiratory exchange ratio (RQ) were made during
      three steady states: control (C) taken after 15 min of normoventilation but
      before CO2 insufflation, after 15 min (L1) and 30 min (L2) of hyperventilation
      during CO2 insufflation. The FIO2 was controlled at 0.5 and arterial blood gases
      were used to calculate the oxygen tension-based indices of pulmonary gas
      exchange. After 15 min and 30 min of CO2 insufflation, the volume of CO2 absorbed
      from the peritoneal cavity was estimated at 42.1 +/- 5.1 and 38.6 +/- 6.6 (SEM)
      ml.min-1 respectively, increasing CO2 elimination through the lungs by about 30%.
      Hyperventilation of the lungs by a 20-30% increase in minute ventilation
      maintained normocapnia. Despite the CO2 pneumoperitoneum and Trendelenburg
      position, there was no impairment of pulmonary oxygen exchange as estimated by (A
      alpha)DO2. This study demonstrated that a 30% increase in minute ventilation,
      achieved by increasing tidal volume to more than 10 ml.kg-1, is sufficient to
      eliminate the increased CO2 load and maintain normal pulmonary O2 exchange during
      pelvic laparoscopy.

PMID- 1394756
TI  - Exposure of operating room personnel to nitrous oxide during paediatric
      anaesthesia.
AB  - This study was undertaken to quantify the exposure of operating room staff to
      nitrous oxide during routine paediatric otolaryngeal surgery and to determine the
      influence of the method of induction of anaesthesia on this exposure. The nitrous
      oxide exposure of the anaesthetist, the surgeon and the circulating nurse were
      measured, using body-worn passive atmospheric samplers, during twelve routine
      paediatric otolaryngeal surgical lists. During six of the lists an inhalational
      technique, with nitrous oxide, oxygen and halothane, was used for the induction
      of anaesthesia. During the other six lists anaesthesia was induced using
      intravenous thiopentone. In all cases, anaesthesia was maintained using nitrous
      oxide, oxygen and halothane. Regardless of the induction technique used, the mean
      nitrous oxide exposures of the anaesthetist, the surgeon and the nurse all
      exceeded the maximum level of 25 ppm.hr-1 recommended by the United States
      National Institute for Occupational Safety and Health (NIOSH). The use of an
      intravenous technique for the induction of anaesthesia reduced the nitrous oxide
      exposure of the anaesthetist and the circulating nurse. This suggests that,
      although the use of an intravenous induction may reduce exposure to nitrous
      oxide, the NIOSH recommendations for maximum exposure of operating room personnel
      to nitrous oxide are currently unattainable in practice.

PMID- 1394757
TI  - Reliability of auscultation in positioning of double-lumen endobronchial tubes.
AB  - Auscultation is a well-established technique to confirm the position of double
      lumen endobronchial tubes (DLTs). However, some authors have recommended that
      fibreoptic bronchoscopy (FOB) is also indicated. The aims of this study were to
      determine first if bronchoscopy after blind placement of DLTs improved
      positioning; and second if preoperative bronchoscopy could detect difficult
      intubation. Twenty-four patients undergoing aortic or lung surgery were studied.
      After intubation with a single-lumen tube, an initial FOB was performed by an
      independent observer to check the airway anatomy. Then, the single-lumen tube was
      replaced by a DLT using a classical "blind" intubation method. Subsequent FOB was
      performed first by the independent observer to record the DLT position and next
      by the investigators for improvement or correction of their positioning under
      visual control. Fibreoptic bronchoscopy after blind placement of DLTs resulted in
      repositioning 78% left-sided DLTs and 83% right-sided DLTs. Preoperative
      bronchoscopy did not always detect an airway abnormality which might lead to
      difficult positioning of the DLTs. In conclusion, auscultation is an unreliable
      method of confirming the position of DLTs and should be followed by fibreoptic
      bronchoscopy.

PMID- 1394758
TI  - Methylparaben and propylparaben do not alter cerebral blood flow in humans.
AB  - In vitro studies suggest that the preservatives methylparaben and propylparaben
      included in some multidose vials of succinylcholine are the cerebral vasodilators
      responsible for the increases in intracranial pressure (ICP) documented after
      succinylcholine administration. To test this hypothesis, we measured cerebral
      blood flow (CBF) and cerebral blood flow velocity (CBFV) with inhaled 133Xenon
      and transcranial Doppler respectively in healthy humans before and after the
      intravenous administration of methylparaben and propylparaben. We found no change
      in either CBF or CBFV after the paraben injections and therefore conclude that it
      is unlikely that the rise in ICP seen with succinylcholine is caused by cerebral
      arterial vasodilatation from the preservatives methylparaben and propylparaben.

PMID- 1394760
TI  - Epidural anaesthesia for caesarean section in an achondroplastic dwarf.
AB  - This report describes the anaesthetic management of an 18-yr-old achondroplastic
      dwarf who presented for elective Caesarean section. Epidural anaesthesia was
      performed without technical difficulty using 8 ml carbonated lidocaine 2% with
      epinephrine 1:200,000. Although the skeletal abnormalities of achondroplasia have
      been cited as contraindications to the use of epidural anaesthesia, clinical
      experience does not support this contention. Previous reports have described
      technical difficulties in these patients, such as dural puncture and inability to
      advance the catheter into the epidural space, but no serious complications
      resulted and epidural anaesthesia was successful on subsequent attempts. The
      existing literature on the anaesthetic management of achondroplasia for Caesarean
      section is reviewed and considerations are presented concerning the choice of
      local anaesthetic, the epidural test dose, and dose titration.

PMID- 1394761
TI  - Anaesthetic considerations in the child with Menkes' syndrome.
AB  - The author presents and discusses the anaesthetic implications of a four-month
      old infant with Menkes' syndrome who required tracheostomy. Menkes' syndrome is
      an X-linked recessive disorder of copper absorption and metabolism. Defective
      processing of copper results in abnormalities of several enzyme systems leading
      to severe dysfunction of multiple organ systems. Due to the progressive nature of
      this disorder and its severe effects on several different organ systems, most
      importantly the central nervous system, these children frequently require
      anaesthetic care during imaging procedures such as MRI or during various surgical
      operations. The high prevalence of seizure disorders, gastroesophageal reflux
      with the risk of aspiration, and airway complications related to poor pharyngeal
      muscle control are of concern to the anaesthetist. In addition, defective
      collagen formation, similar to that seen in Ehlers-Danlos syndrome, may be
      present. Identification of these associated conditions during the preoperative
      examination will guide the selection of appropriate, safe anaesthetic care for
      these children.

PMID- 1394759
TI  - Perioperative haemotherapy: I. Indications for blood component transfusion.
AB  - The practice of transfusion medicine has undergone substantial change over the
      last decade. Much of the impetus for the change has come from the isolation of
      human immunodeficiency virus (HIV) and the linkage of HIV transmission to blood
      transfusion. The purpose of this paper is to collate and review the literature
      relating to the indications for blood transfusion and provide recommendations for
      the appropriate utilization of blood products. Peer-reviewed and published
      studies and reviews relating to aspects of clinical blood transfusion were
      identified through computer searches and searching of the bibliographies of
      identified articles. Emphasis was placed on the literature published within the
      last decade and particularly in the years 1985-91. Material was chosen which was
      of proved clinical importance and in which findings were consistent among
      different investigators or different centres. Less emphasis was placed on
      material reporting new findings of uncertain clinical relevance or findings that
      were not consistent with majority reports. It is concluded that the only
      indication for red cell transfusion is to increase the oxygen carrying capacity
      of the blood and that an adjustment downwards in the haemoglobin concentration at
      which blood is transfused (transfusion trigger) from the traditional level of 100
      g.L-1 is supported by the physiological and clinical data. Perioperative
      haemoglobin concentrations of 80 g.L-1 are acceptable in otherwise healthy young
      patients. The transfusion trigger should be adjusted upwards from this in
      medically compromised patients and in the elderly (greater than 60 yr). Fresh
      frozen plasma (FFP) is only indicated when there are documented deficiencies of
      coagulation factors. Platelet concentrates (PC) are indicated for the treatment
      of clinical coagulopathy resulting from thrombocytopaenia or platelet
      dysfunction. Routine or prophylactic administration of either FFP or PC after
      cardiopulmonary bypass or during resuscitation from haemorrhage is not indicated.

PMID- 1394762
TI  - Development of a computerized database for the study of anaesthesia care.
AB  - To record, tabulate and report problems associated with anaesthesia, we have
      developed an information collection system and computer software to follow all
      patients attended by an anaesthetist at a teaching hospital in Canada. For the
      last 15 mo, data for 17,000 patients have been collected and the system is
      ongoing. Data collection is from three sources: carbonless copies of the
      handwritten Operating Room (OR) and Post Anaesthetic Care Unit (PACU) records,
      other hospital databases, and postoperative visits. Adverse events (observations
      which differ from specific physiological variables, or require an intervention
      and do not normally occur during the routine conduct of anaesthesia), are defined
      directly on each OR and PACU record. These events are recorded when they occur by
      the attending anaesthetist or the PACU nurse. All data are verified by a research
      nurse and an anaesthetist. Computer software, developed from DBase IV, is used to
      track 95 individual items on preoperative status and anaesthetic technique and
      another possible 1,450 selections for drugs, physicians, airways, surgical
      procedures and events for each patient. Data are analyzed with SAS software and
      reports generated to link the casemix and process with outcome. Comparison of
      data entered into the computer programme to a retrospective chart review revealed
      discrepancies of less than 0.5%. Collection, verification and computer entry
      takes five minutes per patient and the on-going cost is estimated at $4 per
      patient record. Analysis of the information collected in this database has been
      useful for research of adverse outcome following anaesthesia, resident expertise
      profiles, and the administrative management of an anaesthesia department.

PMID- 1394763
TI  - Pain syndromes in HIV infection.
AB  - Pain causes considerable disability and discomfort in HIV (Human Immunodeficiency
      Virus) infected individuals. A large number of patients infected with HIV suffer
      from one or more pain-related syndromes. Pain is under-reported and suboptimally
      managed in these patients. An outline of the different pain syndromes, including
      headache, oral cavity pain, chest pain, abdominal pain, anorectal pain,
      musculoskeletal pain and peripheral neuropathic pain, and their aetiologies are
      discussed. Current pain management modalities, including non-narcotic and
      narcotic analgesics, tricyclic antidepressants, anticonvulsants, physical therapy
      and psychological techniques, are outlined. Treatment should be based on the same
      principles applied to the management of cancer-related pain. A multi
      disciplinary, comprehensive approach to pain management will assist these
      individuals to achieve improved levels of comfort, function and quality of life
      in this ultimately terminal illness.

PMID- 1394764
TI  - Effusion after interpleural analgesia.

PMID- 1394765
TI  - The laryngeal mask airway and fibreoptic laryngoscopy.

PMID- 1394766
TI  - Regurgitation and the laryngeal mask.

PMID- 1394767
TI  - Early detection of airway obstruction with a capnographic probe attached to an
      oxygen mask.

PMID- 1394768
TI  - Technology transfer and monitoring practices.

PMID- 1394769
TI  - Transient swelling of the parotid glands following laryngeal mask airway.

PMID- 1394770
TI  - Aspiration and the CMA.

PMID- 1394771
TI  - Complete upper airway obstruction.

PMID- 1394772
TI  - Venous gas embolism during gynaecological laparoscopy.

PMID- 1394773
TI  - Health and the environment: a global challenge. WHO Commission on Health and
      Environment.
AB  - A healthy environment is not only a need, it is also a right; the right to live
      and work in an environment conducive to physical and mental health is enshrined
      in the Universal Declaration of Human Rights. Everyone shares the responsibility
      for ensuring that this right is duly acknowledged. The responsibility for action
      lies with individuals and with business. Governments have the responsibility of
      setting up the strategic and institutional framework within which action is
      taken. There are three main global objectives: achieving a sustainable basis for
      health for all--by slowing down population growth as soon as possible, and
      promoting life-styles and patterns of consumption among affluent groups and
      countries that are consistent with ecological sustainability; providing an
      environment that promotes health--by reducing the risk of physical, chemical and
      biological hazards and ensuring that everyone has the means to acquire the
      resources on which health depends; making all individuals and organizations aware
      of their responsibilities for health and its environmental basis.

PMID- 1394774
TI  - A comparison of group A streptococcal serotypes isolated from the upper
      respiratory tract in the USA and Thailand: implications.
AB  - Characterization of group A beta-haemolytic streptococci in upper respiratory
      tract isolates from the USA and Thailand revealed that whereas 80% of the U.S.
      isolates could be M or opacity factor (OF) typed, less than 20% of the Thai
      isolates could be characterized with the available typing sera (P less than
      0.001). There was also a statistically significant difference observed in the
      percentage of strains that could be characterized by the T-agglutination pattern
      (93% in the USA vs 61% in Thailand, P less than 0.001). Even among the
      identifiable strains, marked differences in the distribution of the recovered
      serotypes were noted between the two countries. These results show that there are
      a significant number of as yet unidentified group A streptococcal strains in
      parts of the world where streptococcal infections and their sequelae are
      important public health problems. They further imply that such findings must be
      taken into consideration in the future when designing possible streptococcal
      vaccines for worldwide use.

PMID- 1394775
TI  - Level of serum antibodies to mycobacterial antigens in healthy Czechs.
AB  - Levels of IgG antibodies to Mycobacterium bovis BCG and M. avium antigens were
      examined by enzyme-linked immunosorbent assay (ELISA) in samples of sera from 898
      healthy adults aged greater than 40 years and 1170 children aged 1-6 years,
      selected at random in 10 districts of Czechoslovakia. The median antibody titre
      to M. bovis BCG in adults ranged from 1:28 to 1:161.7 and that in children from 0
      to 1:50. The mean titres of M. avium antigen ranged from 1:2 to 1:21 in adults
      and from 0 to 1:8 in children.

PMID- 1394776
TI  - Rabies in China: recommendations for control.
AB  - Reviewed are the results of 15 years' experience with rabies at You-An Infectious
      Disease Hospital, Beijing, China. The purpose of the study was to determine
      whether there are any epidemiological or clinical features of rabies that are
      unique to China and which might be important in developing a strategy to control
      it. During the period under study, 64 patients with rabies were admitted to You
      An Hospital. Exposure to dogs was associated with 61 cases, two involving the
      handling of dog carcasses that were being prepared for meals. All of the
      exposures occurred in rural areas, and none of the patients received adequate
      prophylaxis. Patients with proximal sites of exposure and with severe injuries
      developed rabies after short incubation periods (P less than 0.05, and P less
      than 0.02, respectively). Failed vaccination was also associated with a short
      incubation period (P less than 0.05). Haematemesis occurred in 20 patients and
      was associated with shorter incubation periods (P less than 0.02), facial
      exposure sites (P = 0.021), and severe injuries (P = 0.047). A strategy to
      control rabies in China should include efforts to educate the public about
      handling the carcasses of stray dogs, in addition to the currently recommended
      strategy of controlling the dog population and of vaccinating domesticated
      animals.

PMID- 1394777
TI  - [Trachoma in the province of Ouarzazate, Morocco].
AB  - A survey on the prevalence and severity of trachoma was carried out in the
      province of Ouarzazate, Morocco. In conformity with the guidelines proposed by
      the WHO Programme for the Prevention of Blindness, a random sample of 30 clusters
      was extracted from the general population of the province, according to
      probability proportional to size. Thus, the sample comprised 1200 individuals, of
      whom 1185 were examined. Participation in the survey was 98.8% and, overall, the
      sample is considered representative of the province. The simplified grading
      system proposed by WHO was used to register the data on trachoma and its
      complications. The global prevalence of trachoma was estimated at 40.8% (95%
      confidence interval (95% CI) = 30.2-51.4%) and that of active trachoma
      (follicular (TF), intense (TI), and mixed (TF + TI)) at 18% (95% CI = 12.8
      23.2%). The trachomatous intensity indicator (presence of TI) for children under
      10 years of age was 12.8% (95% CI = 6.8-18.8%). The severity of the infection is
      confirmed by prevalences of trichiasis-entropion of 2.2% (95% CI = 1.4-3.0%) and
      central corneal opacity of 3.3%. Corneal blindness is estimated at 1.6%. The
      epidemiological pattern of trachoma merits particular attention in the field of
      public health, particularly in the valley of Oued Draa, where all the indicators
      are consistently higher than those elsewhere in the province.

PMID- 1394778
TI  - Low seroconversion rates to measles vaccine among children in Nigeria.
AB  - The Nigerian Expanded Programme on Immunization (EPI) was assessed with
      particular reference to measles immunization. Of 150 children who received
      measles vaccine at the Institute of Child Health, University of Ibadan, Nigeria,
      82 (54.7%) seroconverted. The immune response was directly related to the titre
      of the vaccines used. Vaccines whose titres were 10(-1) to 10(1.7) stimulated
      immune responses in 0-25% of vaccinees, those with titres in the range 10(-2.1)
      to 10(-2.5) stimulated responses in 12-47.6%, while those with titres of 10(-2.7)
      to 10(-3.4) stimulated responses in 87.5-100% of vaccinees. Only one of the
      vaccines used had a titre that met the minimum WHO required standard of log 10(
      3) TCID50 at the point of vaccination.

PMID- 1394779
TI  - Immunization coverage in India for areas served by the Integrated Child
      Development Services programme. The Integrated Child Development Services
      Consultants.
AB  - The Integrated Child Development Services (ICDS) programme was launched by the
      Indian government in October 1975 to provide a package of health, nutrition and
      informal educational services to mothers and children. In 1988 we studied the
      impact of ICDS on the immunization coverage of children aged 12-24 months and of
      mothers of infants in 19 rural, 8 tribal, and 9 urban ICDS projects that had been
      operational for more than 5 years. Complete coverage with BCG, diphtheria
      pertussis-tetanus (DPT) and poliomyelitis vaccines was recorded for 65%, 63%, and
      64% of children, respectively, in the ICDS population. By comparison, the
      coverage in the non-ICDS group was only 22% for BCG, 28% for DPT, and 27% for
      poliomyelitis. Complete immunization with tetanus toxoid was recorded for 68% of
      the mothers in the ICDS group and for 40% in the non-ICDS group. Coverage was
      greater in the urban and lower in the tribal projects. Scheduled castes,
      scheduled tribes, backward communities, and minorities (groups that have a high
      priority for social services) had immunization coverages in ICDS projects that
      were similar to those of higher castes.

PMID- 1394781
TI  - Evaluating the efficacy of chloroquine in febrile Guinean children infected with
      Plasmodium falciparum by a simplified in vivo test.
AB  - A modified version of a simplified in vivo test was applied to assess the
      susceptibility of Plasmodium falciparum to chloroquine among semi-immune febrile
      children in Kouroussa, Guinea. In 27% of cases, a partial response (RI/RII) to
      chloroquine was observed; the remainder showed a good response (S/RI). This test
      is both practical and useful to assess the efficacy of chloroquine at the
      intermediate level of health care services.

PMID- 1394780
TI  - Breast-feeding, nutritional status, and other prognostic factors for dehydration
      among young children with diarrhoea in Brazil.
AB  - Early identification of children at high risk of diarrhoea-associated dehydration
      would be of great value to health care workers in developing countries. To
      identify prognostic factors for life-threatening dehydration, we carried out a
      case-control study among under-2-year-olds in Porto Alegre, Brazil. Cases were
      192 children admitted to hospital with moderate or severe dehydration, while
      controls were children matched to controls by neighbourhood and age, who
      experienced nondehydrating diarrhoea in the week preceding the interview. The
      following variables were significantly associated with an increased risk of
      dehydration, after adjustment for age and other confounding variables: absence of
      the father from the home; low paternal education level; young age; maternal age
      25-29 years or less than 20 years; mother of mixed race; high birth order; short
      birth interval; low birth weight; stunting, underweight and wasting; lack of
      breast-feeding; presence of other under-5-year-olds in the home; families with 4
      5 members; lack of antenatal care; less than three doses of diphtheria-pertussis
      tetanus or poliomyelitis vaccine; previous admission to hospital; use of
      medicines during the fortnight prior to the episode; and living in an unclean
      home. The associations were particularly strong (P less than 0.001) for the
      child's age, birth weight and other anthropometric indicators, birth interval,
      and feeding mode. In terms of their sensitivity and specificity, however, these
      prognostic factors were not as effective as early signs and symptoms for
      predicting the outcome of the episode.

PMID- 1394782
TI  - Environmental pollution and chronic arsenicosis in south Calcutta.
AB  - Careless handling of industrial wastes often creates problems for human health
      and the environment. Chronic arsenic toxicity, resulting from household use of
      arsenic-contaminated water occurred in 53 out of 79 members (67%) of 17 families
      residing in South Calcutta close to a factory that manufactured Paris-green
      (copper acetoarsenite). Clinical investigation of 20 of these affected persons
      showed typical skin pigmentation as well as palmar and plantar keratosis in all
      of them, while gastrointestinal symptoms, anaemia and signs of liver disease and
      peripheral neuropathy were seen in many. The water used by the affected families
      for drinking and cooking had been taken from shallow tubewells and had arsenic
      levels from 5.0 to 58 mg/l (WHO permissible limit, 0.05 mg/l). Other residents in
      the same area whose drinking-water came from deep tubewells or from tap water
      supplied by the Calcutta Municipal Corporation (arsenic levels, less than 0.05
      mg/l) were not affected. The study confirms that arsenic in the shallow tubewells
      was due to the waste discharged by the factory producing Paris-green.

PMID- 1394783
TI  - Epidemiology's contribution to health service management and planning in
      developing countries: a missing link.
AB  - Two hypotheses are examined in the light of experience and the literature: (1)
      health service planning requires little epidemiological information, and (2)
      health services rarely get useful answers to relevant epidemiological questions.
      In the first hypothesis, the theoretical robustness of the concept of a minimum
      package of activities common to all facilities belonging to the same level of the
      system and the extent to which it is unaffected by variations in the frequencies
      of most diseases are examined. Semi-quantitative analyses and analysis of routine
      entries and participation suffice to adapt this package to the local context.
      Some of the methods which give a fundamental role to epidemiological information
      are criticized. With regard to the second hypothesis, the pertinent contributions
      epidemiology may make to health service organization are reviewed. These include
      identification of diseases that justify special activities (health maps and
      interepidemic surveillance), determination of the activities that should be added
      to the health centres, the political usefulness of rare impact assessments, and
      the relevant demographic elements. Finally an epidemiological agenda is proposed
      for specialized centres, districts, universities, and the central decision-making
      level of health ministries in developing countries.

PMID- 1394784
TI  - Diagnosis of causes of childhood deaths in developing countries by verbal
      autopsy: suggested criteria. The SEARCH Team.
AB  - In the absence of medical certification of deaths in developing countries, lay
      reporting and verbal autopsy have emerged as useful alternative methods for
      collecting data on causes of death. Of these, verbal autopsy offers advantages
      and is widely used in field studies and child survival programmes. However,
      because uniform and valid criteria for the diagnosis of common causes of death
      are lacking, comparison of the results of different studies becomes meaningless.
      This article proposes such a set of criteria for the cause of death among
      neonates and for those aged 1-59 months. The criteria are based on the findings
      of earlier validation studies, a Delphi survey and the experience gained from
      performing 1000 verbal autopsies in Gadchiroli, India. The emergence of such
      standardized criteria of causes of death should be of immense value for health
      planning, monitoring and evaluation purposes and for interregional comparisons.

PMID- 1394785
TI  - Risk factors for injuries due to the 1990 earthquake in Luzon, Philippines.
AB  - On 16 July 1990, an earthquake measuring 7.7 on the Richter scale struck the
      island of Luzon, Philippines. A case-control study was carried out to identify
      the risk factors for earthquake-related injuries and at the same time
      observations were made on the rescue efforts. Being hit by falling objects was
      the leading cause of injury (34%). Those injured during the tremor were more
      likely to have been inside buildings constructed of concrete or mixed materials
      (odds ratio, 2.6; 95% confidence interval (CI), 1.7-4.1) and to have been on the
      middle floors of multistorey buildings (odds ratio, 3.4; 95% CI, 2.2-5.5).
      Leaving a building during the earthquake was a protective behaviour (odds ratio,
      0.3; 95% CI, 0.2-0.8). Of the 235 survivors who were trapped and rescued alive
      from the rubble, 99% were rescued within 48 hours of the impact of the tremor.
      These findings should prove useful in developing seismic safety codes. People
      should be taught proper evasive actions to take during earthquakes, and training
      in basic first aid and methods of rescue should be an integral part of community
      preparedness programmes.

PMID- 1394787
TI  - Nomenclature for human complement component C2. WHO-IUIS Nomenclature Sub
      Committee.
AB  - This note describes the designations for variants of the human complement
      component C2, which were approved by the Nomenclature Committee of the
      International Union of Immunological Societies (IUIS).

PMID- 1394786
TI  - HIV-associated tuberculosis in developing countries: clinical features,
      diagnosis, and treatment.
AB  - This article reviews the clinical aspects and diagnosis of HIV-associated
      tuberculosis in developing countries, and summarizes WHO's recommendations for
      treatment. According to WHO estimates (early 1992) over 4 million persons
      worldwide have been infected with HIV and tuberculosis; 95% of them are in the
      developing countries. Clinical features of HIV-associated pulmonary tuberculosis
      in adults are frequently atypical, particularly in the late stage of HIV
      infection, with non-cavitary disease, lower lobe infiltrates, hilar
      lymphadenopathy and pleural effusion. More typical post-primary tuberculosis with
      upper lobe infiltrates and cavitations is seen in the earlier stages of HIV
      infection. Extrapulmonary tuberculosis is reported more frequently, despite the
      difficulties in diagnosing it. WHO's recent guidelines recommend 6-month short
      course chemotherapy with isoniazid, rifampicin, pyrazinamide and ethambutol for
      patients with HIV-associated tuberculosis. The older 12-month regimen without
      rifampicin is much less effective. Streptomycin should not be used, because of
      the risk of transmitting blood-borne pathogens through contaminated needles.
      Thioacetazone should be abandoned, because of severe adverse reactions observed
      among HIV-infected patients. The roles of preventive chemotherapy and BCG
      vaccination for prevention of tuberculosis are also briefly discussed.

PMID- 1394788
TI  - Revised nomenclature for human complement component C4. WHO-IUIS Nomenclature Sub
      Committee.
AB  - This note describes the recommended designations for allotypes of human
      complement component C4, which were approved by the Nomenclature Committee of the
      International Union of Immunological Societies (IUIS).

PMID- 1394789
TI  - Nomenclature for human complement factor B. WHO-IUIS Nomenclature Sub-Committee.
AB  - In this note is recommended a unified nomenclature for allotypes and variants of
      human complement factor B, which was approved by the Nomenclature Committee of
      the International Union of Immunological Societies (IUIS).

PMID- 1394790
TI  - Recommended composition of influenza virus vaccines for 1992-93.

PMID- 1394791
TI  - Health risks from contaminants in Mediterranean seafood.

PMID- 1394792
TI  - Poliomyelitis and measles: vaccines and immunization.

PMID- 1394793
TI  - The involvement of oncogenes and tumor suppressor genes in the control of
      apoptosis.

PMID- 1394794
TI  - Identification of genes involved in programmed cell death.
AB  - Three modes of activation of apoptosis are described: induction, in which new
      gene expression occurs after the stimulus is applied; transduction, in which gene
      expression is unnecessary at the time of stimulation; and release, in which
      apoptosis is activated by the inhibition of gene expression. Genes activated in
      the induction mechanism were identified by a process of subtractive
      hybridization, whereby newly transcribed messenger RNAs could be isolated.
      Progress in characterizing some of these genes is described. There are many
      difficulties and conceptual problems associated with such a gene cloning
      approach, but the results will be worth the effort.

PMID- 1394796
TI  - The significance of spontaneous and induced apoptosis in the gastrointestinal
      tract of mice.
AB  - The crypts of the gastrointestinal mucosa are highly structured and polarised
      organs with rapid cell proliferation and an hierarchical organisation with
      relatively few stem cells. These tend to be located at specific positions in the
      tissue--at the crypt base in the colon and about four cell positions from the
      base (above the Paneth cells) in the small intestine. A small but constant level
      of spontaneous cell death occurs in the crypt. The levels of cell death are
      elevated by small exposures to radiation or cytotoxic drugs. The morphology of
      the cell death is typical of apoptosis. The maximum yield of cell death following
      cytotoxic exposure is observed at about 3-6 h after treatment and for many agents
      the death is characteristically located at the fourth (stem) cell position in the
      small intestine. The significance and implications of these observations are
      discussed in relation to the internal screening and programming within damage
      cells and with respect to tissue homeostatic mechanisms.

PMID- 1394797
TI  - Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: an
      overview.

PMID- 1394798
TI  - Factors that influence the therapeutic activity of 5-fluorouracil [6RS]leucovorin
      combinations in colon adenocarcinoma xenografts.
AB  - The therapeutic activity of FUra alone or combined with [6RS]LV doses ranging
      from 50 to 1,000 mg/m2 was examined in eight colon adenocarcinoma xenografts, of
      which five were established from adult neoplasms (HxELC2, HxGC3, HxVRC5, HxHC1,
      and HxGC3/c1TK-c3 selected for TK deficiency) and three were derived from
      adolescent tumors (HxSJC3A, HxSJC3B, and HxSJC2). The growth-inhibitory effects
      of FUra were potentiated by higher doses of [6RS]LV (500-1,000 mg/m2) in three
      lines (HxGC3/c1TK-c3, HxSJC3A, and HxSJC3B) and by a low dose of [6RS]LV in only
      one tumor (HxVRC5). Expansion of pools of CH2-H4PteGlun+H4PteGlun (greater than
      or equal to 2.4-fold) in response to higher doses of [6RS]LV was obtained in all
      lines except HxHC1. Metabolism of [6RS]LV was high in HxVRC5, with high levels of
      5-CH3-H4PteGlu being detected, but not in HxHC1, in which levels of 5-CH3
      H4PteGlu and CH = H4PteGlu+10-CHO-H4PteGlu remained relatively low. In the
      adolescent tumors, levels of CH = H4PteGlu+10-CHO-H4PteGlu were consistently
      higher than those of 5-CH3-H4PteGlu following [6RS]LV administration, and in
      HxSJC3A, in which pools of CH2-H4PteGlun+H4PteGlun were significantly expanded, 5
      CH3-H4PteGlu concentrations were lower than those observed in the other two
      lines. The sensitivity of tumors to FUra +/- [6RS]LV and the characteristics of
      [6S]LV metabolism did not correlate with the activity of CH = H4PteGlu
      synthetase, the enzyme responsible for the initial cellular metabolism of [6S]LV
      to CH = H4PteGlu. Thus, no single metabolic phenotype correlated with the [6RS]LV
      induced expansion of CH2-H4PteGlun+H4PteGlun pools. Potentiation of the
      therapeutic efficacy of FUra by [6RS]LV was observed in HxGC3/c1TK-c3 xenografts
      but not in parent HxGC3 tumors, demonstrating the influence of dThd salvage
      capability in the response to FUra-[6RS]LV combinations. Plasma dThd
      concentrations in CBA/CaJ mice were high (1.1 microM). The present data therefore
      demonstrate the importance of (1) higher doses of [6RS]LV, (2) expansion of pools
      of CH2-H4PteGlun+H4PteGlun, and (3) dThd salvage capability in potentiation of
      the therapeutic efficacy of FUra in colon adenocarcinoma xenografts. The plasma
      levels of FUra achieved in mice are presented.

PMID- 1394795
TI  - Apoptosis in the development of the immune system: growth factors, clonal
      selection and bcl-2.
AB  - The mammalian immune system is essential for surviving challenge infections with
      a great range of potential pathogens. The protective effect produced is dependent
      on many different types of cells which require flexible and independent
      production and regulation. In particular, many important responses are carried
      out by lymphocytes, which recognise foreign antigen through exquisitely specific
      receptors: i.e. surface immunoglobulin (sIg) on B lymphocytes and the T cell
      receptor (TCR) on T lymphocytes. Each lymphocyte displays receptors with a single
      specificity, allowing cells with particular specificities to be regulated
      independently. Since millions of different Igs and TCRs are expressed, the
      precise selection and regulation of each T and B cell population to produce a
      useful self-tolerant repertoire is a very complex process. Control of cell
      populations can, in theory, be exercised at a number of levels, including
      modulation of active cell death by apoptosis. Recent research has demonstrated
      that regulation of apoptosis is indeed a crucial element in the control of the
      immune system in general, and in the development of the TCR and Ig repertoires in
      particular. The molecular analysis of apoptosis now takes a high priority and the
      proto-oncogene bcl-2 appears to be responsible for specific suppression of
      apoptosis in several important situations. It is also clear that malfunctions
      affecting apoptosis, and in particular bcl-2, can result in significant
      progression towards malignancy.

PMID- 1394799
TI  - Influence of the cardioprotective agent dexrazoxane on doxorubicin
      pharmacokinetics in the dog.
AB  - The influence of dexrazoxane on doxorubicin pharmacokinetics was investigated in
      four dogs using the two treatment sequences of saline/doxorubicin or
      dexrazoxane/doxorubicin. Intravenous doses of 1.5 mg/kg doxorubicin and 30 mg/kg
      (the 20-fold multiple) dexrazoxane were given separately, with doxorubicin being
      injected within 1 min of the dexrazoxane dose. Both doxorubicin and its 13
      dihydro metabolite doxorubicinol were quantified in plasma and urine using a
      validated high-performance liquid chromatographic (HPLC) fluorescence assay. The
      doxorubicin plasma concentration versus time data were adequately fit by a three
      compartment model. The mean half-lives calculated for the fast and slow
      distributive and terminal elimination phases in the saline/doxorubicin group were
      3.0 +/- 0.5 and 32.2 +/- 12.8 min and 30.0 +/- 4.0 h, respectively. The model
      predicted plasma concentrations were virtually identical for the saline and
      dexrazoxane treatment groups. Analysis of variance of the area under the plasma
      concentration-time curve (AUCo-infinity), terminal elimination rate (lambda z),
      systemic clearance (CLs), and renal clearance (CLr) for the parent drug showed no
      statistically significant difference (P greater than 0.05) between the two
      treatments. Furthermore, the doxorubicinol plasma AUCo-t value and the
      doxorubicinol-to-doxorubicin AUCo-t ratio showed no significant difference,
      demonstrating that dexrazoxane had no effect on the metabolic capacity for
      formation of the 13-dihydro metabolite. The total urinary excretion measured as
      parent drug plus doxorubicinol and the metabolite-to-parent ratio in urine were
      also unaffected by the presence of dexrazoxane. The myelosuppressive effects of
      doxorubicin as determined by WBC monitoring revealed no apparent difference
      between the two treatments. In conclusion, these results show that drug exposure
      was similar for the two treatment arms. No kinetic interaction with dexrazoxane
      suggests that its coadministration is unlikely to modify the safety and/or
      efficacy of doxorubicin.

PMID- 1394800
TI  - Effect of coadministration of selenite on the toxicity and antitumor activity of
      cis-diamminedichloroplatinum (II) given repeatedly to mice.
AB  - The effect of selenite coadministration on the toxicity and antitumor activity of
      repeated treatment with high doses of cis-diamminedichloroplatinum (cis-DDP) was
      examined in mice. Sodium selenite was injected s.c. into separate abdominal sites
      of mice together with cis-DDP at a molar ratio of 1:3.5 (selenite to cis-DDP) on
      day 0. The same amount of selenite was given daily for 4 subsequent days (days 1
      4). This fixed administration schedule was repeated weekly for a total of 7
      weeks. Under the experimental conditions used, the lethal toxicity, renal
      toxicity [indicated by an increase in blood urea nitrogen (BUN) and plasma
      creatinine levels], hepatic toxicity (indicated by an increase in plasma GPT and
      GOT activity), and myelotoxicity (indicated by a decrease in the numbers of
      leukocytes and platelets) observed in mice given repeated doses of cis-DDP alone
      (15 or 25 mumol/kg, s.c.) were significantly depressed by the coadministration of
      sodium selenite. Treatment with cis-DDP alone (15, 20, or 25 mumol/kg, s.c.)
      resulted in some dose-dependent prolongation of the life span of mice
      transplanted either s.c. with colon adenocarcinoma 38 (colon 38) or i.p. with
      P388 leukemia (P388) but did not completely depress the tumor growth, and the
      animals died of either progressive disease or cis-DDP-induced toxicity. However,
      following the coadministration of 7.1 mumol/kg selenite with 25 mumol/kg cis-DDP,
      all of the mice transplanted either s.c. with colon 38 or i.p. with P388 survived
      for as long as 4 months after the end of the treatment and showed no evidence of
      malignancy. These results indicate that selenite coadministration enables the use
      of increasing doses of cis-DDP and, consequently, enhances the antitumor effect
      of cis-DDP by depressing its side effects.

PMID- 1394801
TI  - Lack of involvement of reactive oxygen in the cytotoxicity of mitoxantrone, CI941
      and ametantrone in MCF-7 cells: comparison with doxorubicin.
AB  - The MCF-7 cell S9 fraction and whole MCF-7 cells can mediate one-electron-redox
      cycling of doxorubicin, giving rise to concomitant oxidation of reduced
      nicotinamide adenine dinucleotide phosphate (NADPH), formation of a drug
      semiquinone free radical, consumption of molecular oxygen and formation of
      superoxide anions and hydroxyl radicals. Doxorubicin redox cycling was consistent
      with DNA strand breakage and cell kill in MCF-7 cells. In contrast, no evidence
      for redox cycling was found for mitoxantrone (MIT), CI941 or ametantrone (AMET)
      in MCF-7 cells. Despite the absence of redox cycling, the CI941, MIT, and AMET
      concentrations resulting in 50% mortality (LC50; 1.5 x 10(-10), 5.2 x 10(-9) and
      1.2 x 10(-6) M, respectively) of MCF-7 cells were lower than that of DOX (3.0 x
      10(-6) M). Furthermore, the higher cytotoxicity of MIT and CI941 as compared with
      AMET or DOX was associated with greater efficiency in inducing DNA strand
      breakage in MCF-7 cells as determined by alkaline elution. Since MIT and CI941
      proved to be the most potent DNA-damaging and cytotoxic agents in this study, the
      ability of DOX to undergo redox cycling does not appear to confer increased
      cytotoxic potential on this agent. The present study revealed several important
      aspects with regards to the structural modification of anthraquinone antitumour
      agents. Firstly, the C1 and C4 positioning of the hydroxyethylamino side chains
      on MIT, CI941 and AMET is associated with a lack of flavin reductase-mediated
      activation of these agents. Secondly, the possession of a C5 or C8 aromatic
      hydroxyl group appears to be intimately involved in the enhanced DNA strand
      breakage and cytotoxic potency of MIT and CI941, since AMET does not possess
      these groups. These findings indicate that future development of quinone
      antitumour agents should concentrate on compounds that do not undergo redox
      cycling but do possess aromatic hydroxyl groups, since the latter appear to be
      responsible for the enhanced cytotoxicity of MIT and CI941.

PMID- 1394802
TI  - Activity of aphidicolin glycinate alone or in combination with cisplatin in a
      murine ovarian tumor resistant to cisplatin.
AB  - Aphidicolin, a reversible inhibitor of DNA polymerase alpha and delta, has
      recently been reported to reverse the resistance to cisplatin (DDP) of an ovarian
      cancer cell line. We investigated the pharmacokinetics of aphidicolin in mice and
      examined its activity either alone or in combination with DDP in the DDP
      sensitive M5076 (M5) murine reticular cell sarcoma as well as in a DDP-resistant
      subline (M5/DDP). The drug was cleared from plasma very rapidly (clearance, 41.6
      ml min-1 kg-1), showing a half-life of 15 min. Aphidicolin concentrations in the
      tumor were approximately 50% of those found in plasma at steady state. Using
      several dose schedules and continuous infusions we failed to detect significant
      antitumor activity for aphidicolin glycinate. Potentiation of the activity of DDP
      by aphidicolin glycinate was moderate in mice bearing M5 tumor as well as in
      those bearing M5/DDP tumor. These data do not support the possible clinical use
      of aphidicolin in combination with DDP. However, further studies should be
      carried out in different tumor models before this possibility is conclusively
      ruled out.

PMID- 1394803
TI  - Drug resistance as a dynamic process in a model for multistep gene amplification
      under various levels of selection stringency.
AB  - Resistance to antineoplastic drugs has been a major impediment to the successful
      treatment of cancer. Recent studies suggest that several mechanisms are
      responsible for the emergence of drug resistance but that high levels of
      resistance and poor prognosis are strongly associated with gene or oncogene
      amplification. In this report we describe a probabilistic model for gene
      amplification in a tumor that grows under various drug protocols. The model is
      new in that it treats drug resistance as a dynamic process and examines specific
      assumptions about the underlying molecular events. Using this model, we specify
      the conditions for the emergence of drug-resistant mutants prior to selection as
      well as the relationship between the stringency of the selecting environment and
      the characteristics of the resultant cellular phenotype.

PMID- 1394804
TI  - Adjuvant chemotherapy with vinblastine, adriamycin, and UFT for renal-cell
      carcinoma.
AB  - VAU therapy (vinblastine, Adriamycin, and UFT) was given postoperatively to 31
      patients with stage I, II, or III renal-cell carcinoma, and the incidence of
      relapse as well as the survival of patients were studied. Administration was
      started at 7-14 days post-surgery; 5 mg/m2 vinblastine and 30 mg/m2 Adriamycin
      were given i.v. once every 4 weeks for a total of five courses, and three
      capsules of UFT (containing 300 mg tegafur) were given p.o. every day for 2-3
      years. The postoperative observation period ranged from 2 years and 6 months to 7
      years and 1 month (mean, 4 years and 2 months). The 1-year survival of patients
      was 100%, and the 3- and 5-year survival values were 96%. These results were
      significantly better (P less than 0.01) than the respective values (81%, 72%, and
      60%) obtained for the historical controls, i.e., the 60 patients with stage I,
      II, or III renal-cell carcinoma who received no chemotherapy. Side effects such
      as alopecia, gastrointestinal symptoms, and myelosuppression were encountered,
      but all symptoms were so mild and transient that discontinuation of the treatment
      was not necessary. As VAU therapy might be useful as adjuvant chemotherapy for
      renal-cell carcinoma, it seems to merit further study.

PMID- 1394805
TI  - A preliminary clinical study of gossypol in advanced human cancer.
AB  - A total of 34 patients with advanced cancer were given weekly or daily escalating
      doses of oral gossypol, a cottonseed-oil constituent showing evidence of
      antineoplastic activity in pre-clinical studies. No major adverse events occurred
      and there was no evidence of haematological or biochemical disturbance. As
      determined by dose escalation in 17 patients, the dose-limiting toxicity was
      emesis in 16 patients. There was no evidence of tumour regression in any of the
      20 patients assessed for response. We conclude that gossypol is safe but unlikely
      to be clinically useful in patients with advanced cancer.

PMID- 1394806
TI  - Inhibition of growth factor binding and intracellular Ca2+ signalling by dextran
      sulfates of different sizes and degrees of sulfation.
AB  - The ability of dextran sulfates of varying molecular sizes (5-500 kDa) and
      degrees of sulfate substitution (0.3-1.9) to inhibit the binding of platelet
      derived growth factor (PDGF) to intact Swiss 3T3 fibroblasts and to inhibit
      inositol(1,4,5)trisphosphate-dependent release of Ca2+ in permeabilized Swiss 3T3
      cells was examined in the present study. Significant correlations were found
      between increased molecular size of the dextran sulfates and inhibition of both
      PDGF binding (r = 0.77) and Ca2+ release (r = 0.72). The degree of sulfate
      substitution did not correlate with inhibition of either activity.

PMID- 1394807
TI  - In vivo evidence of complete circumvention of vincristine resistance by a new
      triazinoaminopiperidine derivative S 9788 in P388/VCR leukemia model.
AB  - S 9788, a new triazinoaminopiperidine derivative, was found to be a potent
      reversant of vincristine resistance in the in vivo murine leukemic P388/VCR
      model. In two treatment regimens (Q4D days 1, 5 and 9 and QD days 1-9), S 9788
      enhanced the antitumor activity of vincristine in a dose-dependent manner,
      resulting in a complete circumvention of drug resistance for well-tolerated doses
      of S 9788. S 9788 was also effective in enhancing therapeutic effects of
      vincristine in the treatment of sensitive P388-bearing mice. These results
      strongly suggest that S 9788 may be a potential candidate for circumvention of
      multidrug resistance (MDR) in clinical practice.

PMID- 1394808
TI  - Intra-arterial administration of methotrexate, adriamycin, and cisplatin as
      neoadjuvant chemotherapy for bladder cancer.
AB  - As neoadjuvant chemotherapy for advanced bladder cancer, the intra-arterial
      administration of methotrexate (MTX), Adriamycin (ADM), and cisplatin (CDDP; IA
      MAC) was evaluated. A total of 48 patients with bladder cancer (greater than or
      equal to T2 or CIS) were selected and received 30.1 mg MTX, 34.5 mg ADM, and 89.1
      mg CDDP as an average course. The mean tumor-regression rate after 2 or 3 weeks
      was 52.3%, and patients with grade 3 transitional-cell carcinoma showed the best
      results, achieving a 69.6% regression rate. In 30 cases (63%), downstaging was
      observed. Among the 46 patients who underwent subsequent surgical therapy, the
      bladder could be preserved in 26 cases by transurethral resection or segmental
      resection. According to the criteria of the Japanese Association of Cancer
      Therapy, a histological effect of GIII or better was obtained in 15 cases (29%).
      The histological effect correlated well with the tumor-regression rate. As
      compared with intravenous therapy with MTX, vinblastine, ADM, and CDDP (M-VAC),
      IA-MAC treatment was well tolerated due to its lower degree of bone marrow
      suppression, and it resulted in a longer disease-free interval and better
      survival. In addition, the period prior to surgical therapy was shortened in this
      study. These results suggest that IA-MAC chemotherapy can be useful as an arm of
      multidisciplinary treatment of advanced bladder tumors.

PMID- 1394809
TI  - The 4th study of prophylactic intravesical chemotherapy with adriamycin in the
      treatment of superficial bladder cancer: the experience of the Japanese
      Urological Cancer Research Group for Adriamycin.
AB  - A multicentric randomised trial was conducted for the purpose of investigating
      the efficacy of intravesical chemoprophylaxis of superficial bladder cancers. A
      total of 443 patients (number of evaluable patients, 284) were registered from
      July 1987 to December 1989 and randomised into 3 groups. Group A received 21
      intravesical instillations of Adriamycin (ADM) at 20 mg/40 ml physiological
      saline for 2 years after undergoing transurethral resection (TUR); group B was
      given the same dose as group A but received 6 intravesical instillations for 2
      weeks before undergoing TUR; and group C served as a control and underwent TUR
      only. Better prophylactic effects were obtained in group A. The overall non
      recurrence rates calculated for groups A and B differed significantly (P less
      than 0.05) on day 240, and those determined for groups A and C were also
      significantly different (P less than 0.01) on day 480. No benefit was obtained
      using intravesical instillation prior to TUR (group B). The major side effects
      encountered were pollakisuria and miction pain, which occurred in 32% of the
      patients in group A and in 52% of those in group B.

PMID- 1394810
TI  - Long-term results of intravesical chemoprophylaxis of superficial bladder cancer:
      experience of the Japanese Urological Cancer Research Group for Adriamycin.
AB  - Long-term results were analyzed in terms of tumor progression and survival in
      patients with superficial bladder cancer who were enrolled in the second
      intravesical chemoprophylactic study of the Japanese Urological Cancer Research
      Group for Adriamycin, which was started in July 1982. This study was a
      prospective, randomized, controlled trial conducted on primary tumors treated
      with a long-term instillation regimen that involved control versus intravesical
      instillations of Adriamycin or mitomycin C given once a week for the first 2
      weeks, once every other week for 14 weeks, once a month for 8 months, and once
      every 3 months for 1 year, for a total of 21 instillations in 2 years. An
      analysis of the prophylactic effects of such treatment on bladder tumors after
      TUR has previously been performed, and the results have been published elsewhere.
      The present study represents a follow-up of the above trial. Of the 671 cases
      previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were
      eligible to be followed for tumor progression and survival. A detailed comparison
      of the background factors between these 158 patients and the other 513 cases
      revealed no statistically significant difference. Thus, the 158 evaluable cases
      might reasonably be considered to represent all patients enrolled in the second
      study, and the results were thought to be reasonable enough to reflect the long
      term efficacy of the long-term instillation regimen adopted in this study. The
      median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of
      the disease stage and/or grade occurred in 43 of 127 patients who received
      prophylactic instillations and in 12 of 31 control cases. No significant
      difference in the incidence of tumor progression was found between the treatment
      and the control groups. In addition, no difference in survival was observed
      between the treatment group and the control group. Survival was also compared
      between patients who showed tumor progression and those who did not. All patients
      whose tumors did not progress survived, whereas the 7-year survival of those
      exhibiting tumor progression was less than 90%.

PMID- 1394812
TI  - A prospective randomized study of prophylaxis of tumor recurrence following
      transurethral resection of superficial bladder cancer--intravesical thio-TEPA
      versus oral UFT.
AB  - The long-term prophylactic effect of chemotherapy following transurethral
      electroresection of bladder tumors (TUR-Bt) was investigated using three
      different modalities: no prophylactic treatment (group C); oral UFT given at 1296
      mg/day for 2 years (group U); and intravesical thio-TEPA at 30 mg/30 ml
      physiological saline, instilled 32 times over 2 years (group T). Patients newly
      diagnosed as having superficial bladder cancer (stage, less than or equal to
      pT1b; grade, less than or equal to G2) who had undergone TUR-Bt at Nara Medical
      University and its affiliated hospitals between November 1986 and March 1990 were
      allocated to one of the three groups by the envelope method. The initial
      treatment was maintained until the third recurrence or disease progression,
      except for TUR-Bt which was performed at the time of recurrence. The registered
      cases included 51 patients in group C, 50 in group U, and 52 in group T, and the
      number of evaluable cases in each group were 48, 47, and 45, respectively. The
      non-recurrence rates at 3 years were 54% in group C, 67% in group U, and 85% in
      group T, and the difference between groups T and C was significant. In terms of
      the tumor grade and stage, No significant difference was observed among the
      groups in the category of G1 or Ta tumors, but the non-recurrence rates
      determined in group T for G2 or T1 tumors were significantly higher than those
      obtained in group C. Moreover, no significant difference was found among the
      groups in relation to solitary tumors, but the non-recurrence rate obtained in
      group T for multiple tumors was significantly higher than that determined in
      group C. The overall cumulative recurrence rate in each group was 3.07 in group
      C, 1.95 in group U, and 0.70 in group T, and that determined according to tumor
      grade, stage, and multiplicity was also highest in group C, followed by group U
      and group T. The main adverse effects encountered were upper gastrointestinal
      (GI) symptoms (8.5%) in group U and irritable bladder (11.1%) in group T.
      Intravesical instillation of thio-TEPA tended to produce greater preventive
      efficacy than did oral UFT during the early postoperative period, but the
      prophylactic efficacy of thio-TEPA and UFT should be elucidated over a longer
      observation period.

PMID- 1394811
TI  - Prophylactic chemotherapy for primary and recurrent superficial bladder cancer:
      preliminary results. The Hokkaido University Bladder Cancer Collaborating Group.
AB  - A multicenter trial for postoperative prophylaxis of the recurrence of
      superficial Ta-T1, G1-G2 bladder cancer was performed. Eligible patients with
      primary or recurrent superficial bladder cancer were randomized into four groups.
      For the primary cases, intravesical instillation of drugs [group A, 20 mg
      Adriamycin (ADM) + 200 mg cytosine arabinoside (CA) in 30 ml physiological
      saline; group B, 10 mg peplomycin (PEP) + 200 mg CA in 30 ml physiological
      saline; group C, 2 mg neocarzinostatin (NCS) + 200 mg CA in 30 ml physiological
      saline; and group D, control] was carried out once a week for 2 weeks, once every
      2 weeks for 14 weeks, once monthly for 8 months, and, finally, once every 3
      months for 1 year. For the recurrent cases, intravesical instillation of 20 mg
      ADM + 200 mg CA in 30 ml physiological saline as described above and daily oral
      administration of another drug [group E, 300 mg/day UFT; group F, 200 mg 5
      fluorouracil (5-FU)/day; group G, 30 mg ubenimex/day; and group H, no oral drug]
      was performed. The postoperative follow-up period was 3-36 months. A total of 193
      primary cases and 121 recurrent cases of superficial bladder cancer were
      evaluated. The cumulative 12-month nonrecurrence rates for the primary cases were
      86.2% in group A, 78.1% in group B, 82.1% in group C, and 68.4% in group D. The
      cumulative nonrecurrence rate obtained using ADM+CA (group A) was significantly
      higher than the control value. On the other hand, no significant difference was
      found in the cumulative nonrecurrence rates calculated for the recurrent cases,
      regardless of the oral drug given. Intravesical instillation of ADM+CA for
      primary superficial bladder cancer was considered to be useful, but the long-term
      effect of intravesical instillation remains to be elucidated. Further refinement
      of this regimen is necessary for effective prophylaxis of the recurrence of
      superficial bladder cancer.

PMID- 1394813
TI  - Adjuvant chemotherapy with early intravesical instillation of adriamycin and long
      term oral administration of 5-fluorouracil in superficial bladder cancer. The
      Kyushu University Urological Oncology Group.
AB  - A randomized controlled trial was performed to study the efficiency of adjuvant
      chemotherapy with early intravesical instillation of Adriamycin and long-term
      oral administration of 5-fluorouracil in 275 patients with superficial bladder
      cancer. All of the patients were randomized into four groups. Group A received
      early (immediately and 2 days after transurethral resection) instillation of
      Adriamycin alone; Group B received early instillation of Adriamycin with oral
      administration of 5-fluorouracil; Group C received delayed (7 days after
      transurethral resection) instillation of Adriamycin alone; and group D received
      delayed instillation of Adriamycin with oral administration of 5-fluorouracil.
      All patients subsequently received instillations weekly for 2 weeks and then
      every 2 weeks for a further 14 weeks. After 4 months, they received monthly
      instillations for 8 months. 5-Fluorouracil (groups B and D) was given daily p.o.
      for 1 year. Evaluation was possible in 187 patients. The postoperative follow-up
      period for determination of non-recurrence rates was 36 months, during which no
      significant difference was detected among the four groups. Moreover, no
      statistically significant difference was found between the early- and delayed
      instillation groups. However, the non-recurrence rates obtained in the groups
      undergoing early instillation were higher than those determined in the delayed
      instillation groups during the 36-month follow-up period, and this difference was
      especially significant at 4 and 5 months. In addition, the early-instillation
      groups showed significantly higher non-recurrence rates than did the delayed
      instillation groups in terms of primary cases (P less than 0.01), tumor size of
      less than 1 cm (P less than 0.05), multiple tumors (P less than 0.01),
      pathological stage pTa (P less than 0.01), and histological grades G1 and G2 (P
      less than 0.05). Groups B and D, which were treated by intravesical instillation
      of Adriamycin with oral administration of 5-fluorouracil, showed no significant
      prophylaxis of recurrence during the 36-month follow-up as compared with groups A
      and C, which received intravesical instillations alone. The main side effect,
      which required discontinuation of the treatment, was bladder irritation. However,
      no significant difference in its incidence was found between the early- and
      delayed-instillation groups. No severe systemic side effect was encountered in
      this study. These results suggest that early as well as repeated intravesical
      instillation of Adriamycin is clinically tolerable and may be effective in
      preventing the recurrence of superficial bladder cancer.

PMID- 1394814
TI  - Intravesical combination chemotherapy with mitomycin C and doxorubicin for
      superficial bladder cancer: a randomized trial of maintenance versus no
      maintenance following a complete response.
AB  - Between November 1986 and April 1989, 101 patients with superficial bladder
      cancer were treated with intravesical instillations of mitomycin C on day 1 and
      doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete
      responders, 23 patients with carcinoma in situ and 28 with papillary cancer were
      randomly assigned to a non-maintenance group or to a group receiving maintenance
      therapy consisting of monthly instillations of the same drugs for 12 months. The
      2-year non-recurrence rate calculated for patients with carcinoma in situ was
      significantly better in the maintenance group than in the non-maintenance group.
      A similar tendency was observed for patients with papillary cancer, although the
      difference was not significant. Side effects were considerable, with moderate to
      severe bladder irritation occurring in approximately half of the patients. In
      addition to our previous findings, the present results indicate that this
      intravesical combination chemotherapy is effective in eliminating superficial
      bladder cancers and that since the effect is not durable, even in complete
      responders, maintenance therapy is necessary to reduce subsequent tumor
      recurrence.

PMID- 1394815
TI  - Sequential instillation therapy with mitomycin C and adriamycin for superficial
      bladder cancer.
AB  - Intravesical chemotherapy involving the sequential instillation of mitomycin C
      (MMC) and Adriamycin (ADM) was performed in 40 patients with superficial bladder
      cancer (pathological stages Ta and T1). In all, 20 mg MMC on day 1 and 30 mg ADM
      on day 2 were instilled into the bladder. This treatment was repeated weekly for
      6 consecutive weeks and then monthly for 22 months in cases patients who did not
      experience serious side effects. A total of 20 patients were treated for multiple
      recurrences, and the efficacy was evaluated. In all, 9 subjects (45%) achieved a
      complete response and 6 (30%) showed a partial response, for an overall response
      rate of 75%. The other 20 patients, including 9 with primary multiple or high
      grade tumors and 11 with recurrent tumors, received prophylactic instillation
      therapy after undergoing transurethral resection (TUR) of their lesions. Of the 9
      primary cases, 3 recurred at 19, 8, and 3 months after TUR, respectively, whereas
      6 showed no recurrence over a mean follow-up period of 14 months. Of the 11
      recurrent cases, the 100-patient-month recurrence rate of 11.9 obtained prior to
      this treatment fell to 1.4 after the start of therapy. Chemical cystitis was
      observed in 20 of the 40 patients treated, but the symptoms were transient and
      tolerable.

PMID- 1394816
TI  - Intravesical instillation of adriamycin for bladder tumors.
AB  - In the present series of trials, Adriamycin (ADM) intravesical instillation
      therapy was found to be effective against tumors of papillary morphology
      measuring less than 10 mm in diameter that were of low pathological stage and low
      histological grade. The rate of complete disappearance increased in proportion to
      the concentration of ADM and the duration of retention of the drug, although the
      efficacy rates were almost the same in each trial. On the other hand, side
      effects on the bladder were reduced when the instilled solution was lower in
      concentration and the retention time was short.

PMID- 1394817
TI  - Intra-arterial adriamycin chemotherapy in combination with radiotherapy for
      advanced bladder cancer.
AB  - A total of 38 patients with locally advanced bladder cancer (T2, n = 14; T3, n =
      14; T4, n = 10) were treated with intra-arterial Adriamycin chemotherapy in
      combination with radiotherapy. The clinical as well as the pathological efficacy
      of this treatment was evaluated in all patients. Clinically, 23 (60.5%) of the 38
      patients achieved a complete remission (CR), 12 (31.6%) achieved a partial
      remission (PR), and 3 (7.9%) remained stable (NC). The pathological efficacy was
      evaluated according to the criteria of Shimosato et al., with 20 (52.6%) of the
      38 patients being categorized as grade IV; 2 (5.3%), as grade III; 12 (31.6%) as
      grade II; and 4 (10.5%), as grade 0. The 5-year actuarial survival as a function
      of clinical stage amounted to 91.6% for T2, 50.0% for T3, and 37.4% for T4 (T2 vs
      T3, P less than 0.05; T2 vs T4, P less than 0.01). The 5-year actuarial survival
      determined according to the clinical and the pathological efficacy of treatment
      were 74.1% for CRs, 56.2% for PRs, and 0 for NCs (CR vs NC, P less than 0.01; PR
      vs NC, P less than 0.01). Surgery for preservation of the bladder was performed
      in 30 of the 33 patients who achieved clinical and pathological CRs or PRs. The 5
      year actuarial survival of these 30 patients was 73.2%. These results demonstrate
      that this therapy is a useful method for the treatment of locally advanced
      bladder cancer and that preservation of the bladder might be feasible in patients
      who achieve clinical and pathological CRs or PRs during this treatment.

PMID- 1394818
TI  - Intravesical instillation of adriamycin in the presence or absence of verapamil
      for the treatment of superficial bladder cancer: preliminary report of a
      collaborative study.
AB  - A case-controlled collaborative study on the intravesical administration of
      Adriamycin in the presence or absence of verapamil, a calcium-channel blocker, as
      chemotherapy of superficial bladder cancer was carried out at two universities,
      Okayama and Kagoshima, and their affiliated hospitals. Although little is known
      about the expression of P-glycoprotein in superficial bladder cancer, it may be a
      cause of multidrug resistance (MDR). Verapamil was used as an inhibitor of P
      glycoprotein. Arm A consisted of Adriamycin given at 50 mg/50 ml saline, and arm
      B constituted Adriamycin given at 50 mg/40 ml saline plus 5 ampules (10 ml) of
      injectable verapamil. The drugs were instilled into the bladder for 3 consecutive
      days in each of 3 consecutive weeks for a total of 9 instillations. No
      significant difference in antitumor effects was observed between arm A and arm B.
      Recurrent tumors responded better than did primary tumors to both arm-A and arm-B
      treatments (P = 0.012). In both treatment arms, significant differences (P =
      0.031) in the response rate were found between tumors with diameters of less than
      1 cm and those measuring 1-3 cm in diameter. Although the number of evaluable
      patients was limited, recurrent subjects who had previously received Adriamycin
      instillations responded in both treatment arms.

PMID- 1394819
TI  - Results of adjuvant chemotherapy for invasive uroepithelial cancer.
AB  - Between June 1982 and July 1990, 55 patients (41 with bladder cancers and 14 with
      renal pelvic or ureteral cancers) who had undergone radical extirpative surgery
      and/or node dissection for pathological stage pT2-4 and/or nodal disease received
      adjuvant chemotherapy consisting of cisplatin alone or in combination with other
      agents. In all, 26 of the bladder-cancer patients also received preoperative
      chemotherapy consisting of arterial infusion of cisplatin, mitomycin C, and
      Adriamycin. Adjuvant chemotherapy was performed according to the following
      protocol. Between June 1982 and July 1987, 30-50 mg/m2 cisplatin either alone or
      in combination with Adriamycin and 5-fluorouracil (CAF) was given to 35 patients
      in an induction and maintenance setting for 1 year. After July 1987, short-course
      cisplatin (70 mg/m2) or cisplatin, etoposide, and Adriamycin combination
      chemotherapy (CVA) was given to 20 patients. Of the 55 patients, 38 are alive and
      show no evidence of disease, three are alive with disease, 13 have died of their
      disease, and 1 has died of an unrelated cause. The 5-year survival of all
      patients was 65.1%. The survival of the 20 patients who were treated after July
      1987 was better than that of the 35 patients who were treated before June 1987.
      Local recurrence and/or distant dissemination occurred in 16 patients, 13 of whom
      died of cancer progression. Nausea and vomiting and anorexia occurred in most
      patients during the administration of cisplatin. Mild to moderate
      myelosuppression developed in patients who received CAF or CVA combination
      chemotherapy. Although adjuvant chemotherapy combined with radical surgery seemed
      to be effective in cases with a pathological stage of pT3a or less, more
      intensive pre- or postoperative chemotherapy is needed to improve the poor
      prognosis of patients with deeply invasive uroepithelial cancer.

PMID- 1394820
TI  - Combination chemotherapy for advanced urothelial-tract carcinoma.
AB  - Between December 1982 and November 1990, 31 patients with advanced urothelial
      carcinoma were treated with one of two combination chemotherapy regimens. A total
      of 20 patients were treated with 3 mg/m2 mitomycin C and 300 mg/m2
      cyclophosphamide given intravenously every 10-14 days and with 180 mg/m2 5
      fluorouracil (5-FU) given intravenously every day for as long as possible (CF
      Mito regimen). After the patient had been discharged from the hospital, the same
      treatment with CF-Mito was performed except that 180 mg/m2 5-FU was replaced by
      400 mg/m2 UFT (a mixture of tegafur and uracil) given orally. A total of 11
      patients whose tumor had relapsed during the first-line treatment were given 60
      mg/m2 cisplatin, 40 mg/m2 Adriamycin, and 40 mg/m2 methotrexate intravenously
      every 28 days (PAM regimen). In all, 20 patients received 4-44 (mean, 9.7)
      courses of CF-Mito over a period of 1.5-24 (mean, 5.3) months. The results
      obtained in these 20 patients with evaluable lesions included no complete
      remission (CR), 4 partial remissions (PRs), 9 cases of stable disease (SD), and 7
      cases of progressive disease (PD). The PR duration was 1.5-22 (mean, 7.5) months.
      The side effects encountered in this group included anorexia, nausea, vomiting,
      myelosuppression, diarrhea, stomatitis, liver damage, and heart failure. In all,
      11 patients received 3-7 (mean, 4.1) courses of PAM over a period of 3-14.5
      (mean, 5.2) months. All 11 patients had evaluable lesions, and their responses
      included no CR, 5 PRs, 3 cases of SD, and 3 cases of PD. The PR duration was 1-3
      (mean, 1.6) months. The side effects encountered in this group included anorexia,
      nausea, vomiting, myelosuppression, heart failure, and hair loss.

PMID- 1394821
TI  - Use of methotrexate, vinblastine, adriamycin, and cisplatin in combination with
      radiation and hyperthermia as neo-adjuvant therapy for bladder cancer.
AB  - In an attempt to improve the poor prognosis of invasive and/or high-grade bladder
      cancer after total cystectomy, we tried a combination of regional irradiation
      with hyperthermia (RH) therapy and systemic M-VAC (methotrexate, vinblastine,
      Adriamycin, and cisplatin) chemotherapy followed by surgery. The short-term
      results of these treatments were evaluated. A total of 17 patients received the
      combination of RH and M-VAC therapy between January 1989 and July 1990, and 12
      then underwent total cystectomy. Of the 17 patients, 14 were evaluable for tumor
      response. The objective response rate was 64% (9/14), with 4 patients achieving a
      complete remission that was confirmed by histological examination. Nausea and
      vomiting were inevitable, and 71% (12/17) of the patients developed leukopenia.
      However, these side effects were not serious. Considering the previous results
      obtained using RH therapy in the absence of chemotherapy for this disease, no
      significant difference in the tumor response was detected between the RH only
      group and the RH plus M-VAC group. The long-term results cannot yet be evaluated,
      but we will continue to follow these patients in the future so as to clarify the
      usefulness of M-VAC therapy as preoperative therapy.

PMID- 1394822
TI  - Clinical and pathological evaluations of methotrexate, vinblastine, adriamycin
      and cisplatin chemotherapy for advanced urothelial cancers.
AB  - We have treated advanced transitional-cell carcinoma of the urothelial tract with
      methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) chemotherapy since
      July of 1985. We analyzed the effect of that chemotherapy in 26 patients with
      advanced urothelial cancer who were treated in our hospital and followed up. They
      were divided into two groups. Group 1 consisted of 15 patients with distant
      metastases. In all, 11 of them received M-VAC as adjuvant chemotherapy for
      metastatic lesions after surgical removal of the primary lesion, and the
      remaining 4 patients were not operable since they had very advanced-stage tumors;
      they received only M-VAC chemotherapy. Group 2 contained 11 patients who received
      M-VAC neo-adjuvant chemotherapy. In group 1, the overall response rate was 57.1%
      and the mean duration of response was 12.6 months. In the 11 patients who had
      received M-VAC as adjuvant therapy after surgical removal of the primary tumor,
      the mean duration of response was 14.1 months. After M-VAC chemotherapy, six
      patients underwent surgical resection of metastatic lesions and restaging was
      done pathologically in these cases. The clinical response coincided with the
      pathological response in all six cases. In group 2, 5 of 11 patients experienced
      histological downstaging of the resected bladder. M-VAC chemotherapy combined
      with surgical resection of residual tumors has proved to be an effective option
      against advanced urothelial cancer.

PMID- 1394824
TI  - Factors affecting the outcome of patients with advanced urothelial cancer
      following chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin.
AB  - Attempts were made to identify factors related to the response of patients
      treated with intravenous methotrexate, vinblastine, Adriamycin, and cisplatin (M
      VAC). The subjects consisted of 54 patients with advanced urothelial cancer whose
      histological type was transitional-cell carcinoma. The effects of various factors
      on the response were studied using univariate analysis and a multiple logistic
      regression model. The following factors were included in the analyses: (1) age,
      (2) sex, (3) performance status (PS), (4) primary site, (5) histological grade,
      (6) T category, (7) N category, (8) M category, (9) tumor status, and (10) dose
      of drugs. In all, 9 patients achieved a complete response and 23 showed a partial
      response, for an overall response rate of 59% (95% confidence limits, 46%-72%).
      Univariate analysis revealed that the PS, M category, and dose of drugs were
      related to the response, and there was a significant correlation among these
      three factors. In the multiple logistic regression model, the absolute value of t
      was high for the M category. The presence of distant metastases is an important
      factor in predicting poor efficacy for the present regimen. The management of
      metastatic disease will be the subject of further study in the treatment of
      advanced urothelial cancer.

PMID- 1394823
TI  - Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced urothelial
      cancer.
AB  - A series of 31 patients with advanced urothelial cancer were treated with
      combination chemotherapy consisting of 1-4 cycles of methotrexate, vinblastine,
      doxorubicin, and cisplatin (M-VAC). Of the 31 patients, 29 had measurable and
      evaluable lesions. A complete remission was achieved by 4 of these 29 patients
      (14%) for 1-46 months. A partial remission was observed in 14 of the 29 patients
      (48%) for 1-9 months. Whereas bony and hepatic metastatic lesions did not
      respond, some nodal (7/12), pulmonary (4/8), and pelvic lesions (2/3) as well as
      primary bladder tumors (4/6) and a tumor marker (1/2) responded. Complete tumor
      remission was observed in nodal (2/12) and pulmonary (1/8) metastatic lesions, in
      invasive lesions to the prostate and seminal vesicle (1/1), and in primary
      lesions in the bladder (2/6), ureter (1/1), and urethra (1/1). Two of three
      patients with non-transitional cell tumors attained a partial remission for 1-7
      months. Complete remission of the pulmonary lesions was obtained in a case of
      squamous cell cancer of the bladder with pulmonary metastases. The toxicity of
      this regimen was generally tolerable and included moderate to severe
      myelosuppression, mild to moderate nausea and vomiting, renal toxicity, and
      mucositis. These results suggest that the M-VAC regimen holds promise for the
      treatment of advanced metastatic transitional cell cancer as well as non
      transitional cell cancer of the urothelium.

PMID- 1394825
TI  - Cisplatin-based chemotherapy for the treatment of advanced transitional-cell
      carcinoma of the urinary tract--a preliminary report.
AB  - The CMV (cisplatin, methotrexate, and vinblastine) and M-VAC (methotrexate,
      vinblastine, doxorubicin, and cisplatin) regimens were used to treat 19 patients
      with advanced transitional-cell carcinoma (TCC) of the urothelial tract. In the
      CMV group, the partial response rate was 45.5% and the mean response duration was
      6.3 months. No complete response was obtained in our series. The median duration
      of survival was 15.8 and 8.3 months in responders and nonresponders,
      respectively. The toxic symptoms included one case of sepsis and three cases of
      renal toxicity. However, nausea and vomiting were experienced by most patients
      and required the administration of antiemetics. In the M-VAC group, the median
      duration of survival for responders was longer than that of nonresponders
      (greater than 10.2 vs 7.2 months), although the number of patients was too small
      for this difference to reach statistical significance. The toxic symptoms
      included one case of sepsis, two cases of renal toxicity, and nausea and vomiting
      in most patients. Bone metastasis in three patients did not respond to
      chemotherapy (CMV), a finding that is compatible with the results reported by
      other investigators. In summary, chemotherapy with the CMV or M-VAC regimen was
      effective in improving the response rate of patients. However, the duration of
      response was short, toxicity was severe in some cases, and the efficacy against
      bone lesions was poor. These problems must be solved to improve the outcome of
      patients with TCC following chemotherapy with the CMV or M-VAC regimens.

PMID- 1394826
TI  - Evaluation of systemic chemotherapy with methotrexate, vinblastine, adriamycin,
      and cisplatin for advanced bladder cancer. The Japanese Urological Cancer
      Research Group for Adriamycin.
AB  - In a cooperative study of the Japanese Urological Cancer Research Group for
      Adriamycin, the usefulness of chemotherapy with methotrexate, vinblastine,
      Adriamycin, and cisplatin (M-VAC therapy) in treating advanced or recurrent
      bladder cancer was examined. Evaluation of the clinical responses obtained in 86
      evaluable patients revealed 13 complete responses, 29 partial responses, 4 minor
      responses, 19 cases of no change, and 21 cases of progressive disease. The
      overall response rate was 48.8% (42/86). The rate of response to M-VAC therapy at
      each disease site was as low as 21.4% (3/14) in bone lesions but exceeded 40% in
      the primary lesion, the lymph nodes, the lung, the liver, and other lesions. The
      clinical response to M-VAC therapy was not significantly influenced by the
      performance status of the patients, the dose intensity, or previous therapy. The
      median duration of response for the 42 responders was 22.7 weeks (range, 8.1
      134.1 weeks), and the median duration of survival for the 86 evaluable patients
      was 9.8 months. Side effects were frequently encountered; the patients
      experienced anorexia, nausea, vomiting, malaise, alopecia, and leukopenia, but
      all of these symptoms were tolerable.

PMID- 1394827
TI  - The use of adriamycin and its derivatives in the treatment of prostatic cancer.
AB  - Adriamycin and the other anthracyclines are amongst the most effective cytotoxic
      agents at the clinician's disposal. At least one of the reasons for their
      efficacy is the large number of mechanisms by which they can induce potentially
      lethal damage in a dividing malignant cell. Adriamycin and epirubicin are amongst
      the more effective agents in advanced hormone-independent prostate cancer. When
      given in full doses, they produce a reasonable number of objective as well as
      subjective responses, but the resultant toxicity precludes their use at high dose
      in many patients. In a number of well-documented studies, lower doses of these
      agents have yielded useful subjective responses with minimal toxicity.

PMID- 1394828
TI  - Intravesical therapy with adriamycin and 4-epirubicin for superficial bladder
      cancer: the experience of the EORTC GU Group.
AB  - The anthracycline derivatives Adriamycin and 4-epirubicin are used to prevent
      recurrent tumors after transurethral resection of superficial bladder tumors.
      Both drugs are instilled intravesically. The present report describes the results
      of two multicenter, prospective, randomized phase III studies carried out by the
      EORTC GU Group. In protocol 30,790, after a mean follow-up period of 26.6 months,
      the recurrence rate for 165 patients treated with Adriamycin was 0.29 and the
      tumor rate was 0.74. For 156 patients treated with Epodyl, the recurrence rate
      was 0.29 and the tumor rate was 0.57. This difference was not statistically
      significant. For 70 patients who received transurethral resection alone, the
      recurrence rate was 0.65 and the tumor rate, 2.04. In protocol 30,763, patients
      with good prognostic factors were treated with one single instillation of 4
      epirubicin versus sterile water. After a mean follow-up period of 16 months, in
      190 patients treated with 4-epirubicin the recurrence rate was 0.20 and the tumor
      rate was 0.35; in 196 patients treated with sterile water, the recurrence rate
      was 0.37 and the tumor rate was 0.65 (P = 0.0001). Adriamycin and 4-epirubicin
      were efficacious, and severe side effects were not encountered. The superiority
      of Adriamycin over Epodyl could not be proven.

PMID- 1394830
TI  - Caffeic acid causes metal-dependent damage to cellular and isolated DNA through
      H2O2 formation.
AB  - Pulsed field gel electrophoresis showed that caffeic acid induced DNA strand
      breaks in cultured human cells in the presence of Mn(II). With alkali treatment,
      DNA single-strand breaks were observed. The strand breakage was increased by the
      treatment of buthionine sulphoximine (a GSH synthesis inhibitor) and 3
      aminotriazol (a catalase inhibitor) and decreased by catalase, indicating the
      involvement of H2O2. The DNA damage was decreased by o-phenanthroline, indicating
      the involvement of transition metal ion. Damage to isolated DNA from c-Ha-ras-1
      protooncogene was investigated by a DNA sequencing technique. Caffeic acid caused
      DNA damage in the presence of Cu(II) but not in the presence of either Mn(II) or
      Fe(III). Caffeic acid plus Cu(II) induced piperidine-labile sites frequently at
      thymine residues, especially of the 5'-GTC-3' and 5'-CTG-3' sequences. Typical OH
      scavengers showed no inhibitory effects. The inhibitory effects of bathocuproine
      and catalase on Cu(II)-mediated DNA damage suggest that Cu(I) and H2O2 have
      important roles in the production of active species causing DNA damage. The
      Cu(II)-mediated DNA damage was enhanced by pre-incubation of caffeic acid with
      Mn(II). Mn(II)- or Cu(II)-catalyzed autoxidation of caffeic acid produced H2O2
      with efficiency of Mn(II) greater than Cu(II). These results suggest that in the
      presence of Mn(II) or Cu(II), caffeic acid produces H2O2, which is activated by
      transition metals to cause damage to DNA in vitro and probably in cultured cells.

PMID- 1394829
TI  - Chemotherapy of advanced transitional-cell carcinoma of the bladder.
AB  - A number of single agents and multidrug combinations are useful in the therapy of
      advanced transitional-cell carcinoma of the bladder. Phase II studies have
      identified cisplatin, Adriamycin (doxorubicin), methotrexate, and vinblastine as
      the most active cytotoxic agents. Combination chemotherapy based on cisplatin has
      shown greater efficacy than older regimens based on Adriamycin or methotrexate.
      Trials of regimens containing both cisplatin and methotrexate, such as those
      conducted by the Northern California Oncology Group using CMV (cisplatin,
      methotrexate, and vinblastine), have reported that a significant number of
      patients respond to treatment, with frequent complete responses being noted.
      Anthracycline-containing regimens such as M-VAC (methotrexate, vinblastine,
      Adriamycin, and cisplatin) have also played an important role in the therapy of
      advanced bladder cancer. Trials comparing cisplatin- and methotrexate-containing
      regimens with single-agent cisplatin or other cisplatin combinations have shown
      the apparent superiority of the former in terms of greater overall response rates
      and improved survival. However, the toxicity of such regimens can be significant,
      and phase III studies are under way to validate their use in the neoadjuvant
      setting.

PMID- 1394831
TI  - O6-methylguanine-DNA methyltransferase activity in human tumors.
AB  - The distribution of O6-methylguanine-DNA methyltransferase (MGMT) activity in
      extracts of tumors from 74 patients was measured. The results demonstrated that
      there was considerable variation of MGMT activity in different human tumor
      tissues as well as in different individuals. The mean values (X +/- SD, pmol/mg
      of protein) in breast cancer, stomach cancer, small cell lung cancer, non-small
      cell lung cancer, renal cell carcinoma, esophageal carcinoma, brain tumors, colon
      carcinoma and malignant melanoma were 1.071 +/- 0.374 (9), 0.515 +/- 0.107 (5),
      0.509 +/- 0.251 (5), 0.461 +/- 0.227 (24), 0.329 +/- 0.246 (5), 0.273 +/- 0.376
      (5), 0.244 +/- 0.175 (14), 0.242 +/- 0.308 (5) and 0.201 +/- 0.161 (2)
      respectively. It was notable that six samples (1/24 non-small cell lung cancer,
      3/5 esophageal carcinoma, 1/14 brain tumors and 1/5 colon carcinoma) did not have
      any detectable level of MGMT activity. Activity of glutamine pyruvic transaminase
      (GPT) was also measured in the same extracts used for the assay of MGMT activity.
      The activity of GPT in these samples with undetectable level of MGMT activity was
      similar to those with significant MGMT activity. These results further strengthen
      the assumption that a certain fraction of human tumors are Mer-.

PMID- 1394832
TI  - Aberrant crypts correlate with tumor incidence in F344 rats treated with
      azoxymethane and phytate.
AB  - Aberrant crypts are putative preneoplastic lesions that have been proposed as
      intermediate biomarkers for colon cancer. The goals of these studies were to
      determine (i) if the colon cancer chemopreventive agent, sodium phytate, when
      started 1 week after a single dose of carcinogen, has any effect on the
      development of aberrant crypt foci (ACF) in treated rats; and (ii) if ACF at an
      early time period under these conditions correlate with the later formation of
      tumors in similarly treated animals. The number of ACF with four or more crypts
      was greater (P = 0.02, Mann-Whitney test) in rats with tumors compared with rats
      without tumors killed at 36 weeks after the injection of azoxymethane (AOM); the
      total number of ACF was not significantly different in these two groups. The
      incidence of tumors in F344 rats treated with AOM without phytate was 83% (10/12)
      compared to 25% (3/12) in rats treated with AOM plus phytate (P = 0.0045, two
      tail Fisher's exact test). The finding of more (P = 0.005, Mann-Whitney test) ACF
      with four or more crypts in rats without phytate than in rats with phytate at 12
      weeks after the injection of AOM is consistent with the hypothesis that the
      development of larger ACF (with four or more crypts) is predictive of the tumor
      incidence. These results validate the use of this parameter, i.e. ACF with four
      or more crypts, as an intermediate biomarker for tumor incidence in this system.

PMID- 1394833
TI  - Enhancing effects of diallyl sulfide on hepatocarcinogenesis and inhibitory
      actions of the related diallyl disulfide on colon and renal carcinogenesis in
      rats.
AB  - It has been reported that diallyl sulfide (DS) and diallyl disulfide (DDS), major
      volatile compounds in garlic (Allium sativum), exert anticarcinogenic activity in
      several organs in rodents. The modifying effects of these two chemicals were
      therefore assessed using two-step liver and multi-organ carcinogenesis models. In
      experiment 1, male F344 rats were given a single i.p. injection of N
      diethylnitrosamine (200 mg/kg body wt) and then received DS or DDS by
      intragastric intubation at doses of 200 and 50 mg/kg body wt, respectively, three
      times a week for 6 weeks. All rats were subjected to two-thirds partial
      hepatectomy at experimental week 3. In experiment 2, male F344 rats were
      sequentially treated with five carcinogens with different organ target sites for
      4 weeks, and then administered DS or DDS as in experiment 1 for 24 weeks. DS
      demonstrated clear enhancing effects on the development of glutathione S
      transferase placental form positive foci in both experiments. On the other hand,
      an inhibitory potential in colon and renal carcinogenesis was observed in rats
      treated with DDS. Therefore, while DDS may act as a chemopreventive agent, DS may
      promote hepatocarcinogenesis.

PMID- 1394834
TI  - Azaserine-induced pancreatic foci: detection, growth, labelling index and
      response to raw soya flour.
AB  - Atypical acinar cell foci were induced in the pancreases of rats by injection of
      azaserine. An incubation period of 6 weeks was sufficient for the detection of
      all glutathione S-transferase mu positive foci. In chow-fed rats, the labelling
      index of foci was 12-fold higher than normal pancreatic tissue. Feeding rats raw
      soya flour (RSF) for up to 20 weeks did not increase the number of foci per
      pancreas but did produce significant increases in labelling index and growth
      rate. In normal pancreatic tissue, the trophic response was complete after 4
      weeks of RSF feeding. In foci, however, the trophic response to RSF was
      prolonged. Involution of normal pancreatic tissue was seen in rats fed RSF for 19
      weeks and then switched to chow 1 week prior to death. No evidence for involution
      was seen in the foci of these animals, although a 40-fold reduction was seen in
      labelling index. The labelling index of these foci was reduced to the level seen
      in normal tissue of chow-fed rats. These results are consistent with increased
      cholecystokinin (CCK) responsiveness and CCK dependence in azaserine-induced
      pancreatic foci.

PMID- 1394835
TI  - Effects of cholecystokinin and bombesin on development of azaserine-induced
      pancreatic tumours in rats: modulation by the cholecystokinin receptor antagonist
      lorglumide.
AB  - Cholecystokinin and bombesin have been shown to promote pancreatic growth and
      development of azaserine-induced acidophilic atypical acinar cell nodules in rat
      pancreas after treatment for 16 weeks. Lorglumide, a specific cholecystokinin
      receptor antagonist, inhibited the stimulating effect of cholecystokinin, but not
      of bombesin. The present study was carried out to determine effects of
      cholecystokinin and bombesin, alone and in combination with lorglumide, on
      pancreatic growth and carcinogenesis after chronic treatment. The animals were
      killed 8 months after the start of treatment. Growth of the pancreas and the
      development of acidophilic atypical acinar cell nodules in exocrine pancreas was
      enhanced significantly by both cholecystokinin and bombesin, but the number of
      carcinomas was increased only by bombesin. Lorglumide inhibited the effects of
      cholecystokinin on both pancreatic growth and on the development of acidophilic
      nodules. The effects of bombesin on pancreatic growth and development of
      pancreatic lesions, except for adenomas, were not inhibited by lorglumide.

PMID- 1394836
TI  - Effect of carcinogen dose and age at administration on induction of mammary
      carcinogenesis by 1-methyl-1-nitrosourea.
AB  - The objective of the work reported in this paper was to determine if the
      tumorigenic response to 1-methyl-1-nitrosourea (MNU) in the mammary gland varied
      with age of administration and was dose dependent when the carcinogen was
      injected prior to 50 days of age. Using a recently developed method for mammary
      tumor induction, MNU was injected i.p. at doses ranging from 25 to 75 mg/kg at 35
      days of age or 50 mg/kg at 28, 35 or 42 days of age. Treatment with MNU resulted
      in induction of both benign and malignant mammary tumors. The incidence of
      mammary gland adenocarcinomas was 100% at and above the 50 mg/kg dose of MNU,
      irrespective of the age at which carcinogen was administered. The number of
      cancers increased in proportion to carcinogen dose, whereas cancer latency
      decreased as the MNU dose increased. In rats injected with 50 mg MNU/kg body
      weight at 28, 35 or 42 days of age, differences among groups in cancer incidence,
      number or latency were not statistically significant. Metastases of mammary
      neoplasms to lung, liver and spleen were observed in rats injected with MNU at 35
      or 42 days of age. These data indicate (i) the dose responsiveness of MNU-induced
      mammary carcinogenesis in rats initiated prior to 50 days of age; (ii) the lack
      of effect of age at initiation if prior to 50 days on final tumor outcome; and
      (iii) that the age at which MNU is injected may affect the metastatic potential
      of the mammary carcinomas that are induced.

PMID- 1394837
TI  - Progressive atypia in spontaneous and N-nitrosodiethylamine-induced
      hepatocellular adenomas of C3H/HeNCr mice.
AB  - The progression of hepatocellular adenomas to carcinomas has been less well
      documented in mice than in rats. We studied progression of spontaneous and
      chemically induced hepatocellular adenomas in male C3H/HeNCr mice by image
      analysis. Spontaneous lesions in 15, 18 and 21 month old untreated male C3H/HeNCr
      mice and experimentally induced lesions were examined. Experimental group 1
      received a single i.p. injection of N-nitrosodiethylamine (DEN) (5 mg/kg body wt)
      at 15 days of age. Groups 2 and 3 were injected a second time with DEN at 15 or
      20 weeks of age (75 mg/kg body wt), with interim sacrifices at 11, 16 and 34
      weeks after the second DEN injection. Atypia in adenomas were classified into
      four grades according to cell size, tinctorial changes, cellular pleomorphism and
      trabecular pattern. At earlier stages of the neoplastic process (11 or 16 weeks
      after the second DEN dose), most adenomas were well-differentiated lesions with
      no atypia or focal grade 1 or 2 atypia. At later stages (34 weeks after the
      second DEN dose), a large proportion of hepatocellular tumors were classified as
      adenoma with grade 3 atypia or carcinoma. The proportion of carcinomas in mice
      treated with a second dose of DEN at 20 weeks of age was significantly higher
      than in mice treated with a single dose of DEN or in mice given a second dose of
      DEN at 15 weeks. A positive correlation was found between increase in the size of
      lesions and increased atypia in both spontaneous and DEN-induced lesions and with
      age for spontaneous tumors. These results support the hypothesis that mouse
      hepatocellular adenomas are truly neoplastic lesions in different stages of
      progression toward malignancy.

PMID- 1394838
TI  - Glutathione conjugation of trans-3,4-dihydroxy 1,2-epoxy 1,2,3,4
      tetrahydrobenzo[c]phenanthrene isomers by human glutathione transferases.
AB  - Each of the four stereoisomers of trans-3,4-dihydroxy 1,2-epoxy 1,2,3,4
      tetrahydrobenzo[c]phenanthrene [(+)- and (-)-anti-BPhDE and (+)- and (-)-syn
      BPhDE] has been incubated with the human glutathione transferase (GST) isoenzymes
      GST A1-1, GST M1-1 and GST P1-1, representing class alpha, mu and pi
      respectively, and glutathione (GSH). The conjugates formed were analyzed by HPLC
      and the results demonstrate that all GST isoenzymes catalyze the formation of GSH
      conjugates of all BPhDE isomers. However, a marked variation in catalytic
      efficiencies was observed (0.122-1.28/mM/s). These values are considerably lower
      than those previously estimated for the bay-region diol epoxides of
      benzo[a]pyrene (B[a]P) and human GSTs. The (+)-syn and (-)-anti-BPhDE (1R,2S
      epoxide absolute configuration) were in general better substrates than the
      corresponding 1S,2R-epoxides. In accordance with previous observations with the
      diolepoxides of B[a]P, GST P1-1 was highly selective towards the BPhDE isomer
      with 4R,3S-diol 2S,1R-epoxide absolute configuration, i.e. (-)-anti-BPhDE,
      whereas GST A1-1 and M1-1 preferentially catalyzed the conjugation of (+)-syn
      BPhDE (4R,3S-diol 2R,1S-epoxide absolute configuration). Overall, the most active
      isoenzyme was GST A1-1. Analysis by NMR spectroscopy of the GSH conjugates of
      BPhDE demonstrate that the reaction with GSH generally takes place by trans
      addition of the thiol group at the benzylic C-1 carbon. The low catalytic
      efficiencies of human GSTs with BPhDE as compared to diolepoxides of B[a]P may be
      explained in part by the more crowded bay-region and substantially lower chemical
      reactivity (e.g. delta Edeloc/beta) of the former compounds.

PMID- 1394839
TI  - Endogenous glutathione levels modulate the frequency of both spontaneous and long
      wavelength ultraviolet induced mutations in human cells.
AB  - Spontaneous and induced mutations at the hypoxanthine guanine phosphoribosyl
      transferase locus have been measured in cultured human lymphoblastoid (TK6) cell
      populations under conditions in which cellular glutathione has been severely
      depleted by overnight treatment with buthionine-S,R-sulfoximine. At maximum
      levels of glutathione depletion, the increase in spontaneous frequency is at
      least 5-fold, a finding consistent with the possibility that cellular redox state
      can modulate the levels of pre-mutagenic damage arising as a result of normal
      metabolism in cultured human cells. Glutathione depletion does not lead to a
      significant enhancement in the frequency of mutants that arise as a result of
      irradiation at 313 nm but does lead to a 3-fold increase in mutations resulting
      from irradiation at 365 nm. These results indicate that glutathione may quench
      reactive intermediates that would otherwise lead to spontaneous mutations as well
      as a fraction of UVA radiation-induced premutagenic damage.

PMID- 1394840
TI  - Foreign compound metabolism capacity in man measured from metabolites of dietary
      caffeine.
AB  - Caffeine is sequentially metabolized by cytochrome P4501A2 (CYP1A2), N
      acetyltransferase (NAT) and/or xanthine oxidase (XO). In the present study the
      activity of these three enzymes was estimated from ratios of the metabolites
      formed from dietary caffeine and excreted into the urine collected as spot
      samples. In the urine samples from 10 out of 377 subjects concentrations of
      caffeine metabolites were too low to allow reliable measurements of the ratios.
      In 335 healthy subjects the NAT activity showed a typically bimodal distribution
      with 47% fast acetylators and 53% slow acetylators, consistent with a Danish
      population. The ratios reflecting CYP1A2 and XO activities were log normal and
      normal distributed, respectively. In 103 non-smoking men and 90 non-smoking women
      the ratio of caffeine metabolites expressing CYP1A2 activity was 4.7 +/- 1.6 and
      4.3 +/- 1.9 as compared to 7.8 +/- 2.5 and 7.3 +/- 3.0 in 31 male and 25 female
      subjects smoking 10 cigarettes/day or more respectively, verifying induction of
      CYP1A2 by tobacco (P less than 0.05), but minimal sex-related differences. In 12
      non-smoking pregnant women and in 28 women using oral contraceptives the CYP1A2
      ratio was 29 and 20% reduced respectively (P less than 0.05). In a multivariate
      analysis the only significant predictor of the XO ratio was the consumption of
      caffeine with an increase of 2% per cup of coffee or equivalent (P less than
      0.05). In 23 healthy male subjects 30 days of vigorous exercise increased the
      CYP1A2 ratio by 70% and the XO ratio by 42% (P less than 0.05), but left the NAT
      ratio unchanged. In nine healthy volunteers daily ingestion of 500 g of broccoli
      for 10 days increased the CYP1A2 ratio by an average of 12% (P less than 0.05),
      compared to a control period with ingestion of an equivalent weight of non
      cruciferous green vegetables. The ratios of metabolites from dietary caffeine in
      spot urine samples offer ethical, non-invasive and reliable estimates of CYP1A2,
      NAT and XO. These enzymes are highly relevant for the bioactivation of
      potentially toxic compounds and the formation of oxygen radicals. The method is
      applicable in large-scale epidemiological studies, allowing, for example,
      prospective testing of the relationship between these enzyme activities and the
      development of disease. Exercise may increase CYP1A2 activity to a magnitude
      corresponding to heavy smoking, as well as XO by mechanisms that remain to be
      clarified.

PMID- 1394841
TI  - Coal tar therapy does not influence in vitro benzo[a]pyrene metabolism and DNA
      adduct formation in peripheral blood lymphocytes of psoriatic patients.
AB  - Human lymphocytes (HL) from healthy subjects and psoriatic patients were treated
      in vitro for 24 h with 4 microM [3H]benzo[a]pyrene (B[a]P) and 2 microM (-)-B[a]P
      7,8-dihydrodiol in order to verify if the coal tar (CT) used in the therapy of
      psoriasis, which is characterized by a high content of polycyclic aromatic
      hydrocarbons (PAH), influences the formation of B[a]P-DNA adducts and the
      metabolism of B[a]P. Significant amounts of syn-BPDE-dGuo adducts were detected
      in all the examined HL samples, but no significant difference in the amounts of
      total BPDE-DNA adducts or of specific anti- and syn-BPDE-dGuo adducts was
      observed between healthy subjects and psoriatic patients, or between psoriatic
      patients before and after CT treatment. Moreover, the CT treatment of psoriatic
      patients did not influence the enantiomeric composition of B[a]P-7,8-dihydrodiols
      present in the HL culture medium, among which the (-)-7R,8R form was found to
      predominate (greater than 98%) in all the HL samples. The existence in HL of a
      specific metabolic pathway of B[a]P leading to the formation of (-)-syn-BPDE and
      the corresponding tetrols, through the epoxidation of the (-)-7R,8R enantiomer of
      B[a]P-7,8-dihydrodiol, was confirmed by determining the tetrols derived from the
      syn- and anti-stereoisomers of BPDE, released in HL culture medium after
      treatment for 24 h with 2 microM (-)-B[a]P-7,8-dihydrodiol. Although B[a]P
      7,10/8,9 and B[a]P-7/8,9,10 tetrols, derived from (+)-anti-BPDE, were the
      predominant isomers, significant amounts of B[a]P-7,9/8,10 and B[a]P-7,9,10/8
      tetrols, derived from the hydrolysis of (-)-syn-BPDE, were also detected. The
      mean ratio of anti/syn tetrols in healthy subjects was significantly lower than
      in psoriatic patients, but no difference in that ratio was found in psoriatic
      patients before and after CT treatment.

PMID- 1394842
TI  - Contribution of dihydrodiol dehydrogenase to the metabolism of (+/-)-trans-7,8
      dihydroxy-7,8-dihydrobenzo[a]pyrene in fortified rat liver subcellular fractions.
AB  - Dihydrodiol dehydrogenase (DD; EC 1.3.1.20) purified to homogeneity from rat
      liver cytosol will catalyze the NAD(P)(+)-dependent oxidation of (+/-)-trans-7,8
      dihydroxy-7,8-dihydrobenzo[a]pyrene (B[a]P-diol) to yield benzo[a]pyrene-7,8
      dione (BPQ). To verify that BPQ is a metabolite of B[a]P-diol in rat liver, an
      S100 fraction was supplemented with NAD+ and NADP+, and the formation of BPQ was
      followed by reverse-phase HPLC. The identity of BPQ was established by co
      chromatography with an authentic standard (under different solvent conditions)
      and by RP-HPLC using a diode-array detector which established that the metabolite
      shared spectral identity with BPQ. The formation of BPQ in the S100 fraction was
      blocked by either a competitive inhibitor (indomethacin) or a suicide substrate
      [1-(4-nitrophenyl)-propen-1-ol] for DD, indicating that BPQ was being formed by
      this enzyme. To assess the contribution of DD to the metabolism of [3H]B[a]P
      diol, subcellular fractions obtained from uninduced rat liver were fortified with
      co-factors to optimize the activity of enzymes that would compete for this
      proximate carcinogen. Under these conditions, S100 fractions fortified with NAD+
      and NADP+ metabolized 25% of the B[a]P-diol, producing 731 +/- 154 pmol of BPQ.
      In contrast, rat liver microsomes fortified with an NADPH generating system
      metabolize 75% of the B[a]P-diol producing 2614 +/- 379 pmoles of benzo[a]pyrene
      tetrahydrotetrols. Rat liver homogenates (S10) fortified with either uridine
      diphosphoglucuronic acid or phosphoadenosine phosphosulfate produced 180 +/- 56
      and 95 +/- 31 pmoles of conjugates respectively, which were recovered as B[a]P
      diol after treatment of the aqueous phase with either beta-glucuronidase or aryl
      sulfatase. Of the metabolites analyzed BPQ was formed in the second largest
      amount. These studies show that in uninduced rat liver DD may play a significant
      role in the metabolism of B[a]P-diol. The metabolic fate of BPQ remains to be
      determined.

PMID- 1394843
TI  - Mutagenesis of the K-ras protooncogene in mouse lung tumors induced by N-ethyl-N
      nitrosourea or N-nitrosodiethylamine.
AB  - The role of ras gene activation in the development of lung tumors induced by N
      ethyl-N-nitrosourea (ENU) and N-nitrosodiethylamine (DEN) was evaluated in the
      A/J mouse, a strain susceptible to chemically induced lung tumors. DNAs isolated
      from both ENU- and DEN-induced lung tumors were screened for activating mutations
      in the K-ras gene by utilizing the polymerase chain reaction (PCR) and direct
      sequence analysis. Mutations in the K-ras gene were detected in 11 of 11 ENU
      induced tumors and 23 of 28 DEN-induced tumors. In ENU-induced tumors, there were
      three GC----AT transitions in the second base of codon 12, and seven AT----GC
      transitions and one AT----TA transversion in the second base of codon 61. A
      similar spectrum of K-ras mutations was observed in DEN-induced lung tumors: five
      GC----AT transitions and two GC----TA transversions in the second base of codon
      12, and sixteen AT----GC transitions at the second base of codon 61. Ninety-one
      percent (31/34) of the observed mutations are consistent with the formation of
      the promutagenic O4-ethylthymine and O6-ethylguanine adducts in DNA. Therefore,
      lung tumors from the A/J mouse induced by DEN and ENU could be initiated by the
      interaction of reactive metabolites with specific sites in the K-ras gene. This
      is the first clear example of activation of the K-ras gene by ethylating agents
      in a rodent lung tumor system.

PMID- 1394844
TI  - Characterization of 4,4'-methylenebis(2-chloroaniline)--DNA adducts formed in
      vivo and in vitro.
AB  - 4,4'-Methylenebis(2-chloroaniline) (MOCA) is a genotoxic and carcinogenic
      industrial chemical to which there is considerable potential human exposure.
      Since metabolic activation and formation of DNA adducts are believed to be
      important for the induction of these effects, DNA was treated in vitro with
      radiolabeled N-hydroxy-MOCA, the presumed proximate carcinogenic metabolite
      formed in vivo. Two major radioactive peaks were observed after HPLC separation
      of enzymatic hydrolysates. The two products were analyzed by MS and characterized
      as N-(deoxyadenosine-8-yl)-4-amino-3-chlorobenzyl alcohol and N-(deoxyadenosin-8
      yl)-4-amino-3-chlorotoluene. The same adducts were also the major adducts formed
      in DNA of tissues from rats treated with radiolabeled MOCA. They were eliminated
      from rat liver with non-linear kinetics, in agreement with observations made for
      other carcinogens. The selective reaction of N-hydroxy-MOCA with DNA-adenine and
      the formation of single arylamine ring adducts suggest a substitution mechanism
      involving an intermediate with strong SN1 character, aided by the negative
      inductive effect of the ortho-chlorine. Due to tautomer formation, the initial
      adduct may be inherently unstable and undergo cleavage at the 1'-carbon-methylene
      bond to yield the observed adducts.

PMID- 1394845
TI  - Examination of microsomal cytochrome P450-catalyzed in vitro activation of o
      phenylphenol to DNA binding metabolite(s) by 32P-postlabeling technique.
AB  - It has been previously reported that the reactive metabolites phenylsemiquinone
      and phenylbenzoquinone are generated during microsomal cytochrome P450-catalyzed
      redox cycling of o-phenylphenol (OPP). However, covalent modification of DNA by
      OPP-reactive metabolites has yet not been demonstrated. In the present study we
      have investigated the covalent binding in DNA by OPP-reactive metabolites using
      32P-postlabeling. Analysis of adducts by 32P-postlabeling in products of chemical
      reaction of DNA with phenylbenzoquinone revealed four major and several minor
      adducts. The chemical reaction of deoxyguanosine 3'-phosphate with
      phenylbenzoquinone also showed four major adducts. The chromatographic mobility
      of major adducts of deoxyguanosine 3'-phosphate-phenylbenzoquinone was identical
      to that of major adducts of DNA-phenylbenzoquinone. The major adducts are
      demonstrated to be stable. The total covalent binding in deoxyguanosine 3'
      phosphate by phenylbenzoquinone (686,000-687,000 amol/nmol nucleotide) was higher
      than that observed in DNA (26,500-28,000 amol/nmol nucleotides). Reaction of DNA
      with OPP or a hydroxylated metabolite of OPP, phenylhydroquinone, in the presence
      of microsomes and NADPH or cumene hydroperoxide showed four major adducts. Adduct
      formation in DNA by OPP or phenylhydroquinone in the presence of the microsomal
      activation system was drastically decreased by known inhibitors of cytochrome
      P450. The chromatographic mobility of major adducts in DNA by OPP or
      phenylhydroquinone in the presence of microsomal activation system matched with
      those major adducts observed in deoxyguanosine 3'-phosphate or DNA reacted with
      pure phenylbenzoquinone. These data demonstrate that OPP or phenylhydroquinone, a
      hydroxylated metabolite of OPP, is able to bind covalently to DNA in the presence
      of a microsomal cytochrome P450 activation system. Phenylbenzoquinone is one of
      the DNA-binding metabolite(s) of OPP. It is concluded that OPP is genotoxic in an
      in vitro system and genotoxicity produced by OPP-reactive metabolites may play a
      role in OPP-induced cellular toxicity or cancer.

PMID- 1394846
TI  - Spectrum of mutations in single-stranded DNA phage M13mp2 exposed to sunlight:
      predominance of G-to-C transversion.
AB  - Sunlight is regarded to be a cause of skin cancer, though the mechanisms
      underlying the causation are still unclear. The genotoxic effects of sunlight are
      believed to be induced by pyrimidine photoproducts produced by the action of the
      UV portion of sunlight. However, it is not clear whether these pyrimidine
      modifications are the sole sources for the mutations. In the present study, we
      have analyzed the mutagenic potential of sunlight on the lacZ alpha region of
      single-stranded DNA phage M13mp2 using an SOS-deficient recA- strain and an SOS
      induced rec+ strain of Escherichia coli as hosts. Exposure to sunlight caused
      mutations; approximately 10-fold increases in the mutation frequency were
      observed with the use of both hosts. When SOS functions were induced in the host
      CSH50, the mutation frequencies increased another 10-fold over those obtained
      with the host lacking the SOS functions. DNA sequences of the mutants were
      analyzed by automated DNA sequencers. Sequence changes were identified in 53
      mutants from the mutant DNAs obtained using NR9099 as host and in 78 mutant
      samples obtained using UV-treated CSH50. Most of the mutations were transversions
      of guanine, either G to C or G to T. Furthermore, 59% of the identified sequence
      changes in the SOS- host and 40% of those in the SOS-induced host were G-to-C
      transversions. These transversions may be caused by unidentified guanine damages
      or by the effects of damage at pyrimidines distal from guanines to be mutated.

PMID- 1394847
TI  - Enhanced hprt mutant frequency but no significant difference in mutation spectrum
      between a smoking and a non-smoking human population.
AB  - Recently, we have observed a small (36%), but significant, enhancement of the
      frequency of 6-thioguanine (6-TG)-resistant T-lymphocytes in blood from smokers.
      The molecular nature of 43 hypoxanthine-guanine phosphoribosyltransferase (hprt)
      mutant T-lymphocyte clones from nine smoking individuals was determined to
      investigate whether the increase in hprt mutant frequency would lead to a changed
      mutation spectrum. The types and distribution of hprt mutations in smokers was
      compared with those found in 55 6-TGr T-lymphocyte clones from 12 members of a
      control group of non-smokers. From this control group 25 hprt mutants were novel,
      whereas 31 have been described previously. Among smokers and non-smokers, a
      similar proportion of base substitutions (approximately 35%), mutations causing
      aberrant splicing (approximately 37%), frameshifts (approximately 16%) and
      deletions (approximately 9%) was found. In both groups, GC----AT base pair
      changes were found to be predominant among transitions. However, whereas all
      types of transversions were about equally represented in non-smokers, GC----TA
      transversions were not recovered among smokers. Investigation of the distribution
      of base substitutions over the hprt coding region showed no differences between
      the two groups. These data provide no clues on the nature of DNA adducts induced
      by smoking, which are thought to be responsible for the increased mutation
      frequency at the hprt locus in T-lymphocytes from smokers.

PMID- 1394848
TI  - Species differences in urinary butadiene metabolites; identification of 1,2
      dihydroxy-4-(N-acetylcysteinyl)butane, a novel metabolite of butadiene.
AB  - 1,3-Butadiene (BD) is used in the manufacture of styrene-BD and polybutadiene
      rubber. Differences seen in chronic toxicity studies in the susceptibility of
      B6C3F1 mice and Sprague-Dawley rats to BD raise the question of how to use the
      rodent toxicology data to predict the health risk of BD in humans. The purpose of
      this study was to determine if there are species differences in the metabolism of
      BD to urinary metabolites that might help to explain the differences in the
      toxicity of BD. The major urinary metabolites of BD in F344/N rats, Sprague
      Dawley rats, B6C3F1 mice, Syrian hamsters, and cynomolgus monkeys were identified
      as 1,2-dihydroxy-4-(N-acetylcysteinyl)-butane (I) and the N-acetylcysteine
      conjugate of BD monoxide [1-hydroxy-2-(N-acetylcysteinyl)-3-butene] (II). These
      mercapturic acids are formed by addition of glutathione at either the double bond
      (I) or the epoxide (II) respectively. When exposed to approximately 8000 p.p.m.
      of BD for 2 h, the mice excreted 3-4 times as much metabolite II as I, the
      hamster and the rats produced approximately 1.5 times as much metabolite II as I,
      while the monkeys produced primarily metabolite I. The ratio of formation of
      metabolite I to the total formation of the two mercapturic acids correlated well
      with the known hepatic epoxide hydrolase activity in the different species. These
      data suggest that (i) the availability of the monoepoxide for conjugation with
      glutathione is highest in the mouse, followed by the hamster and the rat, and is
      lowest in the monkey; and (ii) the epoxide availability is inversely related to
      the hepatic activity of epoxide hydrolase, the enzyme that removes the epoxide by
      hydrolysis. The ratio of the two mercapturic acids in human urine following BD
      exposure may indicate the pathways of BD metabolism in humans and may aid in the
      determination of the most appropriate animal model for BD toxicity.

PMID- 1394849
TI  - Dietary hydrogen peroxide enhances hepatocarcinogenesis in trout: correlation
      with 8-hydroxy-2'-deoxyguanosine levels in liver DNA.
AB  - The tumor-enhancing effect of hydrogen peroxide (H2O2) in N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG)-initiated rainbow trout hepatocarcinogenesis was
      investigated and correlated with the levels of the mutagenic DNA adduct 8-hydroxy
      2'-deoxyguanosine (oh8dG). In addition, the protective role of vitamin E was
      examined in relation to tumor enhancement and oh8dG levels in liver DNA. Trout
      were fed diets containing two levels of vitamin E (1000 or 20 mg/kg wet wt), each
      of which were made up to contain three levels of H2O2 (0, 600 or 3000 p.p.m.).
      Dietary vitamin E levels had no significant effect on tumor incidence or levels
      of oh8dG in liver DNA. On the other hand, dietary H2O2 enhanced liver tumors in a
      dose-dependent manner. Liver tumor incidence correlated significantly with the
      mean level of liver DNA oh8dG content (r = 0.87). We conclude that the H2O2 tumor
      enhancing effect coincides with higher levels of oh8dG in the trout liver genome.
      Thus, rainbow trout may be a useful model for the study of the relationship of
      oh8dG levels in vivo to enhancement or promotion of carcinogenesis and its
      modulation by dietary enhancers and inhibitors of oxidative stress.

PMID- 1394850
TI  - Inhibition of repairable DNA-damage in Escherichia coli K-12 cells recovered from
      various organs of nitrosamine-treated mice by vitamin A, phenethylisothiocyanate,
      oleic acid and triolein.
AB  - The influence of various dietary constituents--phenethylisothiocyanate (PEITC),
      oleic acid (OA), triolein (TO), and vitamin A (ROL)--on the genotoxic activity of
      nitrosamines (NDMA, NDELA, NPYR) was investigated. For this purpose differential
      DNA repair assays with Escherichia coli K-12 strains were performed in vitro and
      in vivo with mice. Under in vitro conditions (liquid holding), all compounds
      reduced nitrosamine induced DNA-damage in the indicator bacteria in the dose
      range 1-10 micrograms/ml, the ranking order of efficiency being PEITC greater
      than OA greater than ROL greater than or equal to TO. In animal-mediated assays,
      acute oral treatment with PEITC (17-150 mg/kg), 2 h before nitrosamine
      administration, resulted in a marked decrease of nitrosamine genotoxicity in
      liver, kidneys, lungs and in the blood. Also in other organs (spleen, testes) an
      increase in differential survival (which serves as a measure for repairable DNA
      damage) occurred. With ROL only a comparatively moderate antigenotoxic effect was
      obtained at a high dose level (250 mg/kg) under identical experimental
      conditions. OA (2000 mg/kg) and TO (16,000 mg/kg) were completely inactive. Upon
      repeated treatment (consecutive oral administration of the putative
      antigenotoxins over 4 days, a final treatment 24 h before nitrosamine
      administration) PEITC (150 mg/kg/day), ROL (80 mg/kg/day) and OA (2000 mg/kg/day)
      had no influence on the genotoxic effects of the nitrosamines. Repeated treatment
      with TO (4000-16,000 mg/kg/day) resulted in a moderate dose-dependent reduction
      of NDMA-induced DNA-damage in the indicator bacteria, whereas in combination with
      NPYR only a marginal effect was observed. Biochemical experiments indicated that
      the antigenotoxic effects of PEITC seen under in vivo conditions were due to
      inhibition of alpha-hydroxylation of the nitrosamines, whereas ROL and TO
      appeared not to interfere strongly with this metabolic activation step. Our
      results indicate that in vitro assays do only partly reflect the antigenotoxic
      properties of the different food constituents in vivo and that animal-mediated
      DNA repair assays with E. coli strains are an appropriate approach to study the
      effects of modifiers of nitrosamine genotoxicity in the living animal.

PMID- 1394852
TI  - Formation and 32P-postlabeling of DNA and tRNA adducts derived from peroxidative
      activation of carcinogenic azo dye N,N-dimethyl-4-aminoazobenzene.
AB  - Peroxidase in the presence of hydrogen peroxide catalyzes in vitro the activation
      of carcinogenic N,N-dimethyl-4-aminoazobenzene (DAB) to DNA-, tRNA- and
      homopolydeoxyribonucleotide-bound products. tRNA is the most susceptible to
      modification by the activated DAB. Binding of DAB products to macromolecules is
      inhibited by methyl viologen, nitrosobenzene, ascorbate, glutathione, NADH and
      MgCl2. The mechanism of these inhibitions was studied. The nuclease P1 version of
      the 32P-postlabeling assay was employed for detection and quantitation of some
      major DNA or tRNA adducts formed with DAB activated by a peroxidase system. tRNA
      modified by activated DAB shows a significantly increased acceptance for L
      methionine.

PMID- 1394851
TI  - Ras involvement in cells transformed with 2-amino-4-(5-nitro-2-furyl)thiazole
      (ANFT) in vitro and with N-[4-(5-nitro-2-furyl)-2-thiazoyl]formamide in vivo.
AB  - N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) administration to rats
      followed by sodium saccharin results in transitional cell carcinomas of the
      bladder, of which 24% harbor an activated H-ras gene. Since 2-amino-4-(5-nitro-2
      furyl)thiazole (ANFT) is the mutagenic and carcinogenic metabolite of FANFT in
      vivo, we wished to examine ras activation in in vitro ANFT-transformed rat
      bladder epithelial cells as well as four cell lines established in culture from
      in vivo FANFT-induced rat bladder tumors. Screening by Western blotting revealed
      no enhanced levels of p21ras in ANFT-transformed cells nor in cells established
      in culture from FANFT-induced rat bladder carcinomas. Further investigations
      using immunohistochemical staining with a different pan-reactive p21 monoclonal
      antibody (Cetus Corporation) specific for this method, however, showed two groups
      of cells from FANFT-induced rat bladder tumors had enhanced immunoreactivity.
      Apart from this, p21ras expression of most of the cells groups varied little from
      the controls. We examined the reported hot spots (exons 1 and 2) of each of the
      ras genes (H-, K- and N-ras) by direct sequencing of amplified DNA. No mutations
      were present. We conclude, therefore, that ANFT transformation of primary rat
      bladder epithelial cells in vitro may not in this case be mediated by ras
      activation, although this is difficult to determine since others have observed
      that optimal culture conditions can select for certain populations of cells
      without ras activation.

PMID- 1394853
TI  - Dose-response study on covalent binding to forestomach protein from male F344
      rats following oral administration of [14C]3-BHA.
AB  - A dose-response study on covalent binding to forestomach protein was performed
      using male F344 rats following oral administration of [14C]3-tert-butyl-4
      hydroxyanisole (3-BHA). The order of tissue distribution of radioactivity 6 h
      after oral administration of 1% [14C]3-BHA was forestomach greater than glandular
      stomach greater than liver greater than kidney greater than plasma. The covalent
      binding levels to forestomach protein were very low until 0.1% 3-BHA, but rapidly
      increased at concentrations of 1% and 2% 3-BHA. The dose-response relations of 3
      BHA levels to the covalent binding to protein coincided well with the incidence
      of forestomach papilloma reported previously. The binding levels of forestomach
      and glandular stomach were compared. In case of i.v. administration, both binding
      levels were almost the same, however, in case of 0.1% p.o. administration, the
      forestomach level was approximately 8-fold higher than the glandular stomach
      level. The binding level of forestomach protein by p.o. administration was
      approximately 54-fold higher than that by i.v. administration. Although the
      amount of tert-butylhydroquinone (BHQ) was very low compared with the amount of
      covalent binding, the BHQ levels in forestomach were dependent upon the dose
      levels of 3-BHA. Our study indicates that the dose-response study on covalent
      binding to target tissue protein is an efficient method for the quantitative
      estimation of the active metabolites coming from the chemicals which form the
      quinone metabolites.

PMID- 1394854
TI  - Expressed emotion in parents of non-referred children aged 6 to 11 years from two
      school populations: a pilot study.
AB  - This study investigates the role of parental expressed emotion (EE) in families
      of well-adjusted children. These were randomly selected from two school
      populations representing two different socio-economic backgrounds. Maternal
      criticism was strongly correlated with children's behaviour, although both the EE
      ratings and the scores of children's behaviour were within the established normal
      range. Mothers were more emotionally over-involved but also more positive towards
      their children in manual families. Fathers expressed more warmth towards boys.
      Clinical and methodological issues regarding the concept of EE are discussed.

PMID- 1394855
TI  - Service needs of families of children with severe physical disability.
AB  - Service contacts, perceived helpfulness of services and needs for help were
      investigated in a sample of 107 families of young children with severe physical
      disability. Many families were in contact with a multiplicity of different
      services and overall frequency of contact was high. Despite this, there was
      evidence of considerable unmet need, particularly in the provision of information
      to families. Families with the highest levels of unmet need were likely to have
      experienced high levels of strain from life events and to have children with
      mental retardation as well as physical disability, fathers in those families were
      more likely to be unemployed and mothers were more likely to use passive optimism
      in coping with child problems. The findings indicate the importance of services
      which are easily accessible to parents, the provision of information to parents
      about such services, the co-ordination of services through a 'link' person and
      the accurate and individual assessment of family needs.

PMID- 1394856
TI  - Impaired motor skill (clumsiness) in otherwise normal children: a review.
AB  - Some children, who are otherwise normal, experience unusual difficulties with the
      acquisition and performance of motor skills. These children are commonly
      described as being clumsy. Impaired performance of motor skills, to the degree
      experienced by clumsy children, is unlikely to present a serious problem.
      However, a review of the literature suggests that significant associated and
      secondary emotional problems are common. In particular, such problems are likely
      to result in children not achieving their full potential. Therefore, it is
      important that the cause of affected children's impaired motor skills be
      recognized early so that these problems can be avoided, or at least minimized, by
      a sympathetic understanding of their difficulties. The problem is that, whilst
      severely affected children can be readily recognized, identification of mildly
      and moderately clumsy children is difficult.

PMID- 1394857
TI  - Parental involvement in the KIDS Family Centre: who does it work for?
AB  - Although parental involvement has been a major development in the field of
      disability and handicap, there has been relatively little systematic
      investigation of the value and appreciation of parental involvement from the
      parent's point of view. This study addresses the use and appraisal of services by
      parents at the KIDS Family Centre, Camden, London, which offers a variety of
      family-focused services with differing degrees of parental involvement. The
      evidence showed that the overall appraisal of the Centre was high but, given the
      choice, individual parents selected and appreciated different kinds of parental
      involvement services. Certain family background variables were associated with
      the pattern of selection and rating.

PMID- 1394858
TI  - Review: neurotoxicity of lead.
AB  - 'Lead and its compounds are potentially toxic; the element has no known
      physiological function; it is widely distributed in nature and as a result of
      man's activities' (Lawther Report: DHSS 1980). Concern grew in the late 1970s
      that even low levels of exposure to lead caused adverse changes in children's
      adjustment and academic attainment. This paper traces the rapid developments of
      the past decade in investigating the relationship between body lead burden and
      relevant outcome measures. Research strategies moved from small-scale, clinical
      descriptive studies to large-scale epidemiological studies; from cross-sectional
      studies to longitudinal ones. Agreement had to be reached on how to measure body
      lead burden. Decisions had to be made on which outcome measures to use. Measures
      of global intelligence were complemented by measures of academic attainment,
      emotional adjustment and hyperactivity, as well as by experimental measures of
      more basic psychophysiological functioning. Ways had to be found of dealing
      experimentally and statistically with socioeconomic factors which acted as
      confounds. The investigations were marked by tremendous collaboration between
      investigators, between national agencies and across countries. The methodological
      issues are relevant to the investigation of other toxins and they define a field
      of developmental behavioural toxicology. This case study can act as a model for
      investigating the effects of other environmental toxins and hazards.

PMID- 1394859
TI  - Altered cellular calcium regulation and hepatic glucose production during
      hemorrhagic shock.
AB  - The relationship between intracellular Ca2+ and glucose production in the liver
      during early and late states of hemorrhagic shock was studied. Rats were
      anesthetized with intraperitoneal sodium pentobarbital and both femoral arteries
      and one femoral vein were cannulated. Rats were divided into two groups. One
      group was subjected to hemorrhagic shock by rapid withdrawal of blood to a mean
      arterial pressure of 40 mm Hg and maintained in shock for either 30 or 150 min.
      Rats in the control group were observed for the same time period. Hepatic glucose
      production was evaluated in both groups by a nonrecirculating liver perfusion
      model with and without lactate as a substrate. Intracellular free Ca2+ in
      hepatocytes was measured using the Ca2+ selective indicator Fura-2, under basal
      and epinephrine-stimulated conditions. Hyperglycemia and hyperlacticacidemia were
      observed in vivo at 30 min of hemorrhagic shock, whereas hypoglycemia and
      hyperlacticacidemia were observed at 150 min of shock. Hepatic glucose production
      in isolated perfused livers was significantly depressed at 30 min in animals
      subjected to shock (P less than 0.05). Lactate-induced glucose production was
      significantly attenuated at 30 and 150 min (P less than 0.05). Basal Ca2+, in
      isolated hepatocytes, at 30 and 150 min of hemorrhagic shock was significantly (P
      less than 0.05) higher than in controls. The hemorrhagic shock rat hepatocytes
      failed to evaluate intracellular free Ca2+ upon stimulation with 10(-5) M
      epinephrine. These results demonstrate that hemorrhagic shock is associated with
      an increase in hepatocyte intracellular Ca2+ concentration along with attenuation
      of hormone-mediated mobilization of calcium and substrate specific stimulation of
      hepatic glucose production.

PMID- 1394860
TI  - Early gut ischemia in experimental fecal peritonitis.
AB  - Tissue oxygenation in the gastrointestinal tract was studied in a porcine model
      in which septic shock was induced by fecal peritonitis. The oxygen delivered was
      estimated by measuring the portal venous blood flow and the calculated arterial
      oxygen saturation. The oxygen consumption of the gut, including the pancreas and
      spleen, was monitored by measuring the portal venous blood flow and the
      difference between the calculated arterial oxygen and the measured portal venous
      oxygen saturation. In addition, the oxygenation of the gut mucosa was followed
      via the tonometric technique. Furthermore, lactate was measured in arterial and
      portal blood. The experimental animals were divided into two groups, one control
      (n = 6) and one experimental (n = 6). Peritonitis was introduced by installation
      of a standardized amount of autologous feces into the abdominal cavity. The
      animals were followed for 5 hr. Very early during the course of sepsis there was
      a fall in gut intramucosal pH (pHi), and this was evident before any reduction in
      splanchnic DO2. Furthermore, an early increase in splanchnic VO2 was evident
      simultaneously with the fall in pHi. Arterial pH and lactate were not able to
      detect the inadequate regional tissue oxygenation. It is concluded that pHi
      measured with the tonometric technique is sensitive in detecting gut mucosal
      ischemia, and it is therefore highly likely that tonometry would be a valuable
      method in monitoring severe ill patients.

PMID- 1394861
TI  - Effect of platelet-activating factor antagonist and leukotriene antagonist on
      endotoxin shock in the rat: role of the leukocyte.
AB  - The effects of platelet-activating factor (PAF) antagonist (CV-3988) and
      leukotrienes (LTs) antagonist (ONO-1078) on endotoxin-induced sequelae in the rat
      were assessed. Pretreatment with either CV-3988 (6 mg/kg, i.v.) or ONO-1078 (150
      mg/kg, p.o.) did not improve survival rate following the administration of
      Escherichia coli lipopolysaccharide (LPS) compared with that of control rats
      pretreated with solvents of the drugs. Rats pretreated with both CV-3988 and ONO
      1078 exhibited significantly (P less than 0.01) enhanced survival following
      lipopolysaccharide (LPS) administration. Percentage survivals 48 hr after the
      administration of LPS were 20%, 32%, 24%, and 68% in the pretreatment with
      solvents, CV-3988, ONO-1078, and CV-3988 combined with ONO-1078 groups,
      respectively. Pretreatment with CV-3988 combined with ONO-1078 inhibited the
      change of plasma transaminase 3 hr after LPS administration. The neutropenia, due
      to the administration of vinblastine (1 mg/kg, i.v.), increased the survival rate
      following the administration of LPS without pretreatment with PAF and LT
      antagonists. Antishock action of CV-3988 and ONO-1078 could not be seen in
      neutropenic rats. These data suggest that combined pretreatment with PAF
      antagonist and LT antagonist inhibited leukocyte-mediated tissue injury in LPS
      induced endotoxemia.

PMID- 1394862
TI  - Mechanism of immunoreactive atrial natriuretic factor release in an ovine model
      of endotoxemia.
AB  - We have previously reported an increase in plasma levels of atrial natriuretic
      factor (ANF) in an ovine model of endotoxemia. The purpose of this study was to
      determine if this IR-ANF release was mediated by the increase of right atrial
      pressure (RAP) and right heart volumes concomitantly observed following endotoxin
      (LPS) administration. We studied right ventricular function, renal blood flow
      (RBF), urinary output (UO), urinary clearance of free water (CH20), urinary
      osmolality (UOSM), sodium excretion (UENA), and the plasma IR-ANF concentration
      (radioimmunoassay), following the administration of an E. coli LPS bolus (1
      microgram/kg) with (group O, n = 8) and without (group E, n = 10) pretreatment
      with OKY-046, a selective thromboxane synthetase inhibitor. LPS induced early
      increases in RAP, right ventricular end-systolic (RVESV) and end-diastolic
      (RVEDV) volumes, heart rate (HR), and IR-ANF, and delayed increases in RBF, UO,
      and CH20. OKY-046 prevented the elevation of RAP, RVEDV, and RVESV; however, both
      groups showed virtually identical increases in IR-ANF (E: 20.03 +/- 3.8 to 192.33
      +/- 35.47 pg/ml, O: 17.9 +/- 4.1 to 159.5 +/- 23 pg/ml) as well as an increase of
      HR, RBF, UO, and CH20. The increase in IR-ANF release noted following the
      administration of LPS in an ovine model does not appear to be related to the
      early elevations in right heart volumes or atrial distension.

PMID- 1394863
TI  - Effect of sepsis on intracellular sodium activity, sodium concentration, and
      water content in thermal injured rat.
AB  - The effects of sepsis on intracellular Na+ activity, Na+ concentration, and H2O
      partition in skeletal muscle were investigated in a burn rat model. Studies were
      performed on either postburn day 3 or day 7 during evolving burn wound sepsis.
      Data are compared among 3 groups of rats: burned and infected (BI), burned not
      infected (B), and sham burn (C). After 3 days postburn both Na+ activity and
      concentration decreased in the BI group as compared with B and C groups. By
      postburn day 7, the BI group developed septic shock and had increased
      intracellular Na+ activity and concentration. The resting membrane potentials of
      skeletal muscle cells depolarized. The finding of an increased cell membrane
      relative permeability of Na+ to K+ could account for the increase in Na+ influx
      into cells. In addition, intracellular and total muscle H2O contents decreased
      and extracellular H2O increased. Hypernatremia, hyperchloremia, and
      hyperosmolality were also observed in the BI group. However, the fact that there
      was no significant difference between B and C groups indicates that the late
      derangements were due to septic shock rather than simple burn injury. Thus, the
      deleterious effects of the evolving burn wound sepsis on Na+ homeostasis might be
      due to the detrimental effect of increased intracellular Na+ activity on
      mitochondrial respiratory control with subsequent impairment of cellular
      functions.

PMID- 1394864
TI  - Effect of endotoxicosis on plasma and tissue levels of calcitonin gene-related
      peptide.
AB  - This study was designed to investigate the changes in tissue content and plasma
      concentrations of CGRP, a 37 amino acid vasoactive peptide, in male Sprague
      Dawley rats injected intravenously with a nonlethal dose of 3 mg/kg E. coli
      endotoxin. Plasma CGRP concentrations in nonendotoxemic animals, measured by a
      specific RIA, were initially 30.5 +/- 3.3 pg/ml, and were significantly increased
      to 63.7 +/- 4.6 pg/ml 2 hr after induction of endotoxemia (P less than 0.001; n =
      13). A higher dose of LPS did not further elevate plasma CGRP levels, indicating
      that the maximal response occurred following a dose of 3 mg/kg LPS. CGRP levels
      in abdominal aorta, inferior vena cava, stomach, kidney, and left ventricular
      myocardium (4.11, 8.5, 2.61, 0.69, and 0.25 pmol/g wet weight tissue,
      respectively) were not changed significantly following the injection of
      endotoxin. However, in lung and mesenteric artery the levels increased
      significantly from 1.47 +/- 0.12 and 7.97 +/- 1.32 pmol/g wet weight tissue to
      1.96 +/- 0.19 (P less than 0.05, n = 11) and 15.02 +/- 2.3 pmol/g (P less than
      0.01; n = 7), respectively. In contrast, CGRP levels in the duodenum were
      significantly decreased from 11.3 +/- 0.93 pmol/g wet weight tissue to 6.2 +/-
      0.68 pmol/g (P less than 0.001; n = 6). The changes in plasma concentration and
      tissue content of CGRP suggest that splanchnic organs may be the source of the
      elevated plasma CGRP levels in endotoxemia and that selective organ CGRP levels
      reflect a role in the pathogenesis of the response to endotoxemia.

PMID- 1394865
TI  - Reactivity of monoclonal antibody E5 with endotoxin. I. Binding to lipid A and
      rough lipopolysaccharides.
AB  - The murine IgM monoclonal antibody (mAb) E5 was produced by a hybridoma derived
      from spleen cells of a mouse immunized with the J5 rough mutant of Escherichia
      coli O111:B4. In a multicenter randomized placebo-controlled clinical trial, E5
      has been shown to reduce significantly the mortality and morbidity of patients
      with Gram-negative sepsis. The characteristics of E5 binding to endotoxin were
      studied in vitro. We report here the results of binding to an extensive panel of
      rough lipopolysaccharide (LPS) and lipid A preparations. Using standard
      immunologic techniques, including enzyme-linked immunosorbent assay (ELISA) and
      radioimmunoassay (RIA), as well as an antibody capture assay using immobilized
      antibody and a chromogenic Limulus amebocyte lysate (LAL) detection system, E5
      was shown to bind to all rough LPS (chemotypes Ra through Re from Salmonella
      minnesota and E. coli J5) and lipid A preparations tested. E5 displayed a Kd for
      Ra LPS of approximately 6.5 nM. These results confirm and extend those reported
      previously and provide evidence that E5 binds specifically to lipid A and to the
      lipid A moiety of rough LPS.

PMID- 1394866
TI  - In vivo assessment of regional microvascular albumin leakage during E. coli
      septic shock in the baboon model.
AB  - Changes in regional microvascular albumin flux during septic shock were studied
      noninvasively by scintigraphy in the baboon model. Use was made of an i.v.
      injection of 99mTc-labeled baboon serum albumin. Count ratios of lung to cardiac,
      liver to cardiac, and abdominal to cardiac regions were measured two-hourly for 6
      hr in six control and six septic shock baboons (live E. coli) and compared.
      Increased ratios obtained during shock pointed to an increase in extravascular
      albumin. Linear regression lines fitted to these count ratios provided regional
      albumin leak indices. These indices demonstrated statistically significant
      increases (P less than 0.05) during septic shock for the abdominal region during
      the 6-hr study, and for all regions, but especially the abdomen, when data were
      calculated over 4 hr. Increasing ratios and leak indices correlated with
      postmortem data and with changes in neutrophil and platelet behaviour previously
      established during shock. Possible accompanying mediator releases could be
      responsible for the endothelial damage leading to the increased permeability.

PMID- 1394867
TI  - Mouse phospholamban gene expression during development in vivo and in vitro.
AB  - To establish a murine model that may allow for definition of the precise role of
      phospholamban in myocardial contractility through selective perturbations in the
      phospholamban gene, we initiated studies on the role of phospholamban in the
      murine heart. Intact beating hearts were perfused in the absence or presence of
      isoproterenol, and quantitative measurements of cardiac performance were
      obtained. Isoproterenol stimulation was associated with increases in the affinity
      of the sarcoplasmic reticulum Ca2+ pump for Ca2+ that were due to phospholamban
      phosphorylation. To assess the regulation of phospholamban gene expression during
      murine development, Northern blot and polymerase chain reaction analyses were
      used. Phospholamban mRNA was first detected in murine embryos on the ninth day of
      development (the time when the cardiac tube begins to contract). In murine
      embryoid bodies, which have been shown to recapitulate several aspects of
      cardiogenesis, phospholamban mRNA was detected on the seventh day (the time when
      spontaneous contractions are first observed). Only those embryoid bodies that
      exhibited contractions expressed phospholamban transcripts, and these were
      accompanied by expression of the protein, as revealed by immunofluorescence
      microscopy. Sequence analysis of the cDNA encoding phospholamban in embryoid
      bodies indicated complete homology to that in adult hearts. The deduced amino
      acid sequence of murine phospholamban was identical to rabbit cardiac
      phospholamban but different from dog cardiac and human cardiac phospholamban by
      one amino acid. These data suggest that phospholamban, the regulator of the
      Ca(2+)-ATPase in cardiac sarcoplasmic reticulum, is present very early in murine
      cardiogenesis in utero and in vitro, and this may constitute an important
      determinant for proper development of myocardial contractility.

PMID- 1394868
TI  - Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and
      brain natriuretic peptide in cultured rat atrial cells.
AB  - To investigate the cellular mechanism for the synthesis and secretion of atrial
      natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we examined the
      effects of vasoactive agents on the secretion rates and gene expression of ANP
      and BNP in cultured rat atrial cells. Endothelin (10(-7) M, +61%), 12-O
      tetradecanoylphorbol 13-acetate (TPA, 10(-6) M, +62%), the calcium ionophore
      A23187 (10(-6) M, +95%), and Bay K 8644 (10(-6) M, +34%) (p < 0.05 each) all
      increased the secretion of ANP into the culture media in a dose-dependent
      fashion. On the other hand, endothelin (10(-7) M, +57%) and TPA (10(-6) M, +55%)
      (p < 0.01 each) increased the secretion of BNP in a dose-dependent manner,
      whereas A23187 (10(-6) M, -45%, p < 0.001) suppressed the secretion of BNP in a
      dose-dependent manner, and Bay K 8644 caused no significant effects on BNP
      secretion. The molecular forms of intracellular ANP were exclusively gamma-ANP,
      whereas those of BNP were gamma-BNP and its carboxy terminal 45-amino-acid
      peptide, BNP-45. The ratio of media to cell contents was much higher in BNP than
      in ANP. Northern blot analysis revealed that both ANP mRNA and BNP mRNA levels
      were significantly increased by 10(-7) M endothelin (ANP mRNA, +52%; BNP mRNA,
      +36%; p < 0.05 each) and 5 x 10(-5) M 1-oleoyl-2-acetylglycerol (ANP mRNA, +296%;
      BNP mRNA, +133%; p < 0.01 each) but not by 10(-6) M A23187. Thus, the secretion
      of ANP is stimulated by both the elevation of [Ca2+]i and the activation of
      protein kinase C, whereas its synthesis is increased mainly by the activation of
      protein kinase C. The synthesis and secretion of BNP are augmented by the
      activation of protein kinase C rather than the elevation of [Ca2+]i. Furthermore,
      the processing and secretion of ANP and BNP may be regulated in different
      manners.

PMID- 1394869
TI  - Brain ouabain-like activity and the sympathoexcitatory and pressor effects of
      central sodium in rats.
AB  - Intracerebroventricularly infused hypertonic saline elicits sympathoexcitatory
      and pressor effects. To clarify the mechanisms mediating these effects, we
      evaluated blood pressure (BP), heart rate (HR), and renal sympathetic nerve
      activity (RSNA) responses to intracerebroventricular administration of 0.3 M
      NaCl, ouabain, and rat hypothalamic and pituitary extracts containing ouabain
      like activity (OLA) in conscious Wistar rats, before and after
      intracerebroventricular preinjection of digoxin-specific antibody Fab (DAF)
      fragments. To exclude modulatory effects of arginine vasopressin (AVP), treatment
      with DAF fragments was in all experiments preceded by intravenous injection of
      the AVP antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1,o- Me
      Tyr2,Arg8]AVP. After AVP antagonist pretreatment, 0.3 M NaCl i.c.v. at 3.8
      microliters/min for 10 minutes caused simultaneous increases in BP, RSNA, and HR.
      After AVP antagonist pretreatment, intracerebroventricular injections of 0.3 and
      1.0 microgram/l microliter ouabain or the OLA equivalent to 1 microgram ouabain/2
      microliters elicited similar significant increases in BP, HR, and RSNA. After
      pretreatment with AVP antagonist and DAF fragments (66 micrograms/4 microliters
      i.c.v.), BP, HR, and RSNA responses to 0.3 M NaCl, ouabain, and OLA were all
      significantly diminished. In contrast, combined AVP blockade and DAF fragments
      did not affect the BP response to intracerebroventricular angiotensin II, the BP,
      HR, and RSNA response to intracerebroventricular carbachol and to air stress, or
      the HR and RSNA responses to intravenous sodium nitroprusside.
      Intracerebroventricularly injected gamma-globulins (66 micrograms/4 microliters)
      did not affect the responses to 0.3 M NaCl, ouabain, or OLA.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1394870
TI  - Product inhibition of the actomyosin subfragment-1 ATPase in skeletal, cardiac,
      and smooth muscle.
AB  - We studied product inhibition of the actin-activated ATPase of myosin subfragment
      1 (S-1) from the three types of muscle tissue: skeletal, cardiac, and smooth.
      Increasing levels of [MgADP] in the 0-1-mM range caused significant inhibition of
      the actin-activated MgATPase activity of cardiac and gizzard but not skeletal
      muscle S-1. When total nucleotide concentration ([ATP] + [ADP]) was kept constant
      at 1 mM, ATPase activity was inhibited by 50% at an ADP/ATP ratio of 6:1 for
      cardiac S-1 and 3:1 for gizzard S-1. For skeletal S-1, however, even a 19:1 ratio
      did not cause 50% inhibition of ATPase activity. The observed effect was not due
      to changes in pH or inorganic phosphate concentration, nor could it be explained
      by substrate (ATP) depletion. In the absence of actin, ADP had little or no
      inhibitory effect on the ATPase activity of S-1, and these observations imply
      that ADP is competing directly for the ATP binding site of the actin-S1 complexes
      of cardiac and smooth muscle S-1. ADP has previously been shown to be a weak
      competitive inhibitor of the ATPase activity in skeletal muscle. The current data
      imply that ADP is a very effective competitive inhibitor for the actin-activated
      ATPase activity of cardiac and gizzard S-1 and, therefore, that ADP may be a
      physiologically important modulator of contractile activity in cardiac and smooth
      muscle.

PMID- 1394871
TI  - Sympathetic stimulation and norepinephrine infusion modulate extracellular
      potassium concentration during acute myocardial ischemia.
AB  - The purpose of this study was to investigate whether sympathetic stimulation
      modulated the rise in extracellular K+ concentration ([K+]o) evoked by acute
      myocardial ischemia. In 35 alpha-chloralose-anesthetized dogs, we measured
      changes in [K+]o during acute myocardial ischemia in the presence and absence of
      sympathetic stimulation or norepinephrine infusion. A series of four 5-minute
      occlusions of the distal left anterior descending coronary artery (LAD) was
      completed in 18 dogs. Thirty minutes of reperfusion separated each LAD occlusion.
      Four to five K(+)-sensitive electrodes were inserted into the left ventricular
      midmyocardium that was perfused by the distal LAD. Lead II of the
      electrocardiogram, arterial pressure, and [K+]o were recorded, and the right
      atrium was paced at a constant cycle length. The first, second, and fourth LAD
      occlusions were done in the absence of sympathetic stimulation or norepinephrine
      infusion. The changes in [K+]o evoked by the first LAD occlusion differed (p <
      0.05) from those elicited by the second and fourth occlusions. However, the
      changes in [K+]o during the second and fourth LAD occlusions were similar (p >
      0.2) and served as controls for the responses obtained during the third
      occlusion. Two minutes before the third LAD occlusion, sympathetic stimulation (4
      Hz) or norepinephrine infusion (0.25-0.5 micrograms/kg per minute i.v.) was begun
      and was continued until 2 minutes after reperfusion. We found that sympathetic
      stimulation and norepinephrine infusion increased (p < 0.05) myocardial blood
      flow in both normal and ischemic tissue. The mean response recorded by 23 K(+)
      sensitive electrodes in 11 dogs showed that sympathetic stimulation increased (p
      < 0.001) the [K+]o at 1, 2, 3, 4, and 5 minutes after the onset of LAD occlusion
      compared with the second and fourth occlusions. In contrast, the mean response
      recorded by 20 K(+)-sensitive electrodes in seven dogs showed that norepinephrine
      infusion reduced (p < 0.02) the [K+]o at 4 and 5 minutes after the onset of LAD
      occlusion. These data show that sympathetic stimulation increased the [K+]o
      evoked by acute myocardial ischemia, an effect that was not mimicked by the
      intravenous administration of norepinephrine.

PMID- 1394872
TI  - Adenosine A1 receptor activation attenuates cardiac injury produced by hydrogen
      peroxide.
AB  - Adenosine has been shown to protect the ischemic and reperfused myocardium. To
      examine whether the protective effect of the nucleoside is mediated by modulation
      of oxidative stress, isolated rat hearts were perfused for 30 minutes with 100
      microM H2O2 or an exogenous free radical-generating system consisting of purine
      (3.06 mM) and xanthine oxidase (10 units/l) in the presence or absence of drugs
      acting on adenosine A1 or A2 receptors. H2O2 alone produced a greater than 90%
      loss in contractility concomitant with a threefold elevation in resting tension,
      although these effects occurred in the absence of ultrastructural damage. Two A1
      receptor agonists N6-cyclopentyladenosine (CPA, 1 microM) and R(-)-N6-(2
      phenylisopropyl)adenosine (R-PIA, 1 microM) significantly attenuated the
      cardiodepressant effects of H2O2 and depressed the elevation in resting tension;
      however, only the effect of CPA was found to be significant with regard to the
      latter parameter. A similar concentration of S(+)-N6-(2-phenylisopropyl)adenosine
      (S-PIA), a markedly less potent A1 receptor agonist, was found to be without
      beneficial effect. However, a significant protective effect against both the
      reduction in contractility and the elevation in resting tension was seen with a
      10-fold elevation in the concentration of S-PIA (10 microM). The protective
      effects on functional parameters were associated with preservation of high-energy
      phosphate and adenine nucleotide contents after 30 minutes of H2O2 treatment. The
      salutary effects of all drugs were reversed in the presence of the A1 receptor
      antagonist 1,3-dipropyl-8-cyclopentylxanthine (0.5 microM). An A2 receptor
      agonist 2-[p-(carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine, termed
      CGS 21680 (1 microM), failed to alter the cardiac response to H2O2 with regard to
      all parameters studied. Neither a 50% reduction in external CaCl2 concentration
      nor treatment with 10 microM DL-propranolol exerted salutary effects against H2O2
      induced dysfunction. None of the A1 receptor agonists modulated the response to
      purine plus xanthine oxidase. Our results demonstrate a selective protective
      effect of adenosine A1 receptor activation against the cardiac toxicity of H2O2
      and provide, at least in part, a basis for the cardioprotective actions of
      adenosine and its analogues.

PMID- 1394873
TI  - Myocardial energetics during ventricular fibrillation investigated by
      magnetization transfer nuclear magnetic resonance spectroscopy.
AB  - Ventricular fibrillation (VF) is known to produce alterations in myocardial
      energetics, but the mechanism of these changes remains unclear. To investigate
      energy metabolism during VF, phosphorus nuclear magnetic resonance spectroscopy
      and magnetization transfer were applied to isolated perfused ferret hearts. VF
      was induced either by perfusion with digitalis (strophanthidin, 30 microM) or by
      high-frequency electrical stimulation. We measured the flux in two critical
      reactions: from inorganic phosphate (Pi) to ATP (ATP synthesis rate) and from
      phosphocreatine (PCr) to ATP (energy transfer capacity). During digitalis-induced
      VF, energy-related phosphates showed changes similar to those during hypoxia:
      myocardial [Pi] increased and [PCr] decreased. Concomitantly, the ATP synthesis
      rate increased to levels about threefold higher than control, whereas oxygen
      consumption increased by only 16%. The ATP synthesis rate exhibited a strong
      negative correlation with left ventricular pressure during VF (r = -0.95, n = 5,
      p < 0.02), whereas oxygen consumption did not (r = 0.19, p > 0.05). On the other
      hand, energy transfer capacity catalyzed by creatine kinase was significantly
      smaller during VF than in the control condition but still higher than the
      simultaneous ATP synthesis rate. In contrast to the marked energetic
      deterioration during VF induced by digitalis, electrically induced VF led to only
      a small increase in [Pi] and a small decrease in [PCr], and there were no
      significant changes in the ATP synthesis rate, energy transfer capacity, or O2
      consumption. These results indicate that the rundown in energy metabolism during
      VF induced by digitalis was mainly attributable to a limitation of energy
      production through oxidative phosphorylation as well as to a marked increase in
      energy consumption. In contrast, myocardial energy generation remained unimpaired
      during VF induced by electrical stimulation. Intracellular calcium overload is
      more severe during VF induced by digitalis than during electrically induced VF
      (Circ Res 1991;68:1378-1389); severe calcium overload would be expected to
      compromise the capacity for energy generation by mitochondria. Thus, we propose
      that known differences in cellular calcium loading underlie the discrepant
      energetic patterns of the two types of VF.

PMID- 1394874
TI  - Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.
AB  - To investigate the mechanism underlying postischemic cardiac dysfunction
      (myocardial stunning), contractility and adenine nucleotide metabolism were
      studied in three groups of isolated perfused rabbit hearts (control, ischemic,
      and reperfused), whereas Ca2+ uptake by the sarcoplasmic reticulum (SR) was
      measured in homogenates obtained from them. The hearts were Langendorff-perfused
      under constant pressure with Krebs-Henseleit solution at 37 degrees C. Global
      normothermic ischemia was produced by closing the perfusion line. In the
      reperfused group, after 15 minutes of ischemia, Krebs-Henseleit solution was
      perfused for 10 minutes. Developed left ventricular pressure (control, 104 +/-
      6.3 mm Hg) and left ventricular dP/dt (2,063 +/- 256.6 mm Hg.sec-1) were
      significantly decreased in reperfused hearts (left ventricular pressure, 78 +/-
      5.9 mm Hg; left ventricular dP/dt, 1,339 +/- 216.3 mm Hg.sec-1). Myocardial ATP
      content (control, 13.6 +/- 0.98 mumol/g dry wt) decreased during ischemia (4.5 +/
      1.23 mumol/g) but was restored to control level on reperfusion (11.8 +/- 0.68
      mumol/g). Maximum velocity of Ca2+ uptake by the SR (Vmax) (control, 49.3 +/-
      2.54 nmol.min-1 x mg-1) was significantly depressed by ischemia (36.3 +/- 1.94
      nmol.min-1 x mg-1) but was restored to the control value after a 10-minute
      reperfusion (45.3 +/- 0.79 nmol.min-1 x mg-1). Apparent dissociation constant KCa
      and the Hill coefficient for Ca2+ uptake were not different between control,
      ischemia, and reperfusion. To test for the possible role of the SR Ca(2+)-release
      channel in the effect of ischemia and reperfusion, we measured Ca2+ uptake after
      incubation of homogenates with 610 microM ryanodine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1394875
TI  - Reperfusion arrhythmias in isolated perfused pig hearts. Inhomogeneities in
      extracellular potassium, ST and TQ potentials, and transmembrane action
      potentials.
AB  - We recorded direct current electrograms and local [K+]o at multiple sites and
      transmembrane potentials at selected sites during reperfusion after 5 minutes and
      10 minutes of regional ischemia in isolated perfused pig hearts. After 10 minutes
      of ischemia, the incidence of ventricular fibrillation (VF) was 38%. At 80-90
      seconds after reperfusion, [K+]o was 0.8 mM less than in normal tissue in half of
      the reperfused tissue, especially in the border zone. This was associated with TQ
      elevation of +4.5 mV and large peaked T waves. The latter was caused by an abrupt
      decrease of action potential duration in reperfused tissue, leading to a
      difference of up to 165 msec with normal tissue. Reperfusion VF started with a
      closely coupled ventricular premature beat. Activation block between reperfused
      and normal tissue permitted reentrant activation, leading to VF. Pretreatment
      with ryanodine (10(-6) M) and reperfusion with elevated [K+] (both of which
      prevent delayed afterdepolarizations) did not prevent closely coupled ventricular
      premature beats or VF. Five minutes of ischemia never caused VF. K+ depletion and
      TQ elevation in the reperfused zone was less frequent and smaller (-0.4 mM and
      1.8 mV, respectively). Peaked T waves did not occur, and shortening of the action
      potential duration was less. We conclude that extracellular K+ depletion and
      marked action potential duration shortening in the reperfused tissue play a role
      in the genesis of reperfusion VF, which is caused by reentry. The closely coupled
      ventricular premature beat that initiates reentry is not caused by delayed
      afterdepolarizations but most likely by intramural reentry.

PMID- 1394876
TI  - Culture of renal arteriolar smooth muscle cells. Mitogenic responses to
      angiotensin II.
AB  - We cultured smooth muscle cells from rat renal preglomerular arterioles by
      injecting a suspension of iron oxide into the left ventricle, separating the
      arterioles magnetically, and growing cells from explants. In passaged cultures we
      ascertained vascular smooth muscle purity of > 98% by morphology; contraction to
      norepinephrine and angiotensin; positive immunofluorescence staining through the
      sixth passage with monoclonal antibodies to smooth muscle-specific alpha- and
      gamma-isoactins, myosin, and desmin; and the absence of von Willebrand factor.
      Angiotensin II (10(-12)-10(-5) M) induced dose-dependent DNA synthesis and
      proliferation of subcultured (three times) arteriolar smooth muscle cells from a
      growth-arrested state (p < 0.01). Angiotensin II (10(-5) M) also induced the
      cells to express c-fos mRNA. We find no previous report of culture of smooth
      muscle cells from renal preglomerular arterioles. Our findings also provide
      evidence that angiotensin II is mitogenic to arteriolar muscle cells and thus may
      be involved in their hyperplasia accompanying hypertension.

PMID- 1394877
TI  - Relation between vasa recta blood flow and renal interstitial hydrostatic
      pressure during pressure natriuresis.
AB  - Pressure natriuresis may be mediated through increases in inner medullary vasa
      recta blood flow (QVR). By means of acute renal decapsulation to prevent
      increases in renal interstitial hydrostatic pressure (RIHP), the effect of
      increases in QVR in the presence and absence of changes in RIHP in the
      natriuretic and diuretic responses to increases in renal perfusion pressure (RPP)
      was evaluated. Blood flow in descending (QDVR) and ascending (QAVR) vasa recta
      was determined in the exposed papilla by fluorescence videomicroscopy in
      anesthetized euvolemic Munich Wistar rats. In rats with intact renal capsules (n
      = 12), increases in RPP from 101 +/- 0.5 to 132 +/- 2.9 mm Hg caused significant
      increases in QDVR (from 4.7 +/- 0.9 to 5.5 +/- 0.9 nl/min, p < 0.001) and QAVR
      (from 2.8 +/- 0.2 to 3.5 +/- 0.2 nl/min, p < 0.001) in association with increases
      in RIHP (from 4.6 +/- 1.3 to 7.6 +/- 1.3 mm Hg, p < 0.001), urine flow (from 16.2
      +/- 2.6 to 20.2 +/- 3.2 microliters.min-1 x g kidney wt-1, p < 0.01), and urinary
      sodium excretion (from 2.10 +/- 0.38 to 3.36 +/- 0.62 mu eq.min-1 x g kidney wt
      1, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394878
TI  - Partial coronary stenosis is sufficient and complete reperfusion is mandatory for
      preconditioning the canine heart.
AB  - Repeated brief episodes of total coronary artery occlusion (i.e., severe
      ischemia), each separated by brief periods of reperfusion, reduce infarct size
      after a subsequent sustained ischemia. The importance of the intensity of
      ischemia during these coronary artery occlusions and the role of the following
      transient reflow are poorly understood. Therefore, our objective was to determine
      whether moderate preconditioning ischemia induced by partial coronary artery
      stenosis (reducing coronary flow to approximately 50% of its baseline values),
      with or without a brief period of total reperfusion, could precondition the
      canine myocardium. Dogs were randomized to receive one of three preconditioning
      "treatments": the R(-) group underwent 15 minutes of partial coronary stenosis
      without subsequent brief reperfusion (n = 8); the R(+) group underwent 15 minutes
      of partial coronary stenosis followed by 10 minutes of full reflow (n = 8); and
      the control group underwent no intervention (n = 8). All dogs then underwent 1
      hour of total coronary artery occlusion and 4.5 hours of reperfusion. Both
      treated groups were equally and moderately ischemic during partial stenosis:
      myocardial blood flow in the inner two thirds of the left ventricular wall
      averaged 0.25 +/- 0.05 and 0.31 +/- 0.07 ml/min per gram in the R(-) and R(+)
      groups, respectively (p = NS). Furthermore, all three groups were equally and
      severely ischemic during sustained total occlusion: myocardial blood flow in the
      inner two thirds of the left ventricular wall averaged 0.06 +/- 0.05, 0.05 +/-
      0.03, and 0.07 +/- 0.03 ml/min/g in control, R(-), and R(+) groups, respectively
      (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394879
TI  - Ejection load changes in aortic stenosis. Observations made after balloon aortic
      valvuloplasty.
AB  - To investigate complementarity and competitiveness between the intrinsic and
      extrinsic components of the total left ventricular systolic load, hemodynamic
      data from 18 elderly subjects with severe aortic stenosis were analyzed before
      and after balloon dilation of the stenosed aortic valve. Multisensor
      micromanometric pressure measurements allowed calculation (simplified Bernoulli
      equation) of the ejection velocity and aortic input impedance spectra. Despite a
      32% increase in the aortic valve area (from 0.56 +/- 0.04 to 0.74 +/- 0.05 cm2
      [mean +/- SEM], p < 0.01), the peak left ventricular systolic pressure fell by
      only 12% (from 189 +/- 10 to 167 +/- 8 mm Hg, p < 0.01). This was accompanied by
      an increase in the impedance at the same cardiac output. In a subset of patients
      (n = 9) in whom the peak aortic systolic pressure rose after valvuloplasty (from
      115 +/- 10 to 128 +/- 12 mm Hg, p < 0.01), a 40% increase in the aortic valve
      area was accompanied by a marked increase in the aortic input impedance. In this
      subset, the steady component of the aortic input impedance increased by 24% (from
      960 +/- 96 to 1,188 +/- 134 dyne.sec/ml, p < 0.05), and the characteristic
      impedance increased by 25% (from 106 +/- 13 to 132 +/- 19 dyne.sec/ml, p < 0.05).
      Because of an increased aortic impedance acutely following the procedure, the
      total left ventricular systolic load after balloon dilation of the stenotic valve
      was only slightly decreased despite a significant increase in aortic valve area.
      This represents an example of complementarity and competitiveness between the
      intrinsic and extrinsic components of the total systolic ventricular load. It may
      explain why improvement in left ventricular performance may be modest acutely
      following balloon aortic valvuloplasty.

PMID- 1394880
TI  - Branching patterns in the porcine coronary arterial tree. Estimation of flow
      heterogeneity.
AB  - The aim of this study is to quantify the porcine coronary arterial branching
      pattern and to use this quantification for the interpretation of flow
      heterogeneity. Two casts of the coronary arterial tree were made at diastolic
      arrest and maximal dilation. The relation between length and diameter of arterial
      segments was quantified, as well as the area expansion ratio and diameter
      symmetry of vascular nodes. These relations were used to construct computer
      models of the coronary arterial tree, covering diameters between 10 and 500
      microns. Topology of these simulated trees was analyzed using Strahler ordering:
      Bifurcation ratio, diameter ratio, and length ratio were constant along orders 2
      8 and equal to 3.30, 1.51, and 1.63, respectively. In each order, the number of
      segments per Strahler vessel was almost geometrically distributed. For the lowest
      orders, these predictions were confirmed by direct observations. From the network
      model, local pressure and flow were also predicted: Pressure fell from 90 to 32
      mm Hg at the 10-microns level. The coefficient of variation (CV) of flow in
      individual segments was dependent on the number of perfused terminal segments
      (Nt) according to the fractal relation CV(Nt) approximately Nt(1-D), where D is
      the fractal dimension (1.20). CV of flow in 1-g tissue units was predicted to be
      18%. This study shows that the structure of the coronary arterial bed is an
      important determinant of the fractal nature of local flow heterogeneity.

PMID- 1394881
TI  - Brain death-induced impairment of cardiac contractile performance can be reversed
      by explantation and may not preclude the use of hearts for transplantation.
AB  - The shortage of suitable donor hearts for cardiac transplantation is exacerbated
      by the exclusion of those that exhibit contractile malfunction during the period
      after brain death but before excision. We have replicated the phenomenon of brain
      death-induced hemodynamic deterioration in the rat in vivo. After 60 minutes of
      brain death (defined as the absence of electrical activity in the brain), a
      variety of indicators of cardiac contractile function fell by approximately 50%
      (thus cardiac index fell from 21 +/- 2 to 11 +/- 1 ml/min per 100 g body weight).
      However, once excised and perfused ex vivo, the hearts recovered a level of
      cardiac function that was identical to that from control animals that had not
      been subjected to brain death. Similarly, when hearts were excised, stored (6
      hours at 4 degrees C), and reperfused ex vivo with blood, they also recovered a
      functional capability identical to that of normal hearts from animals that had
      not been subjected to brain death. Our results question whether hemodynamic
      instability in brain-dead individuals is necessarily an irreversible detrimental
      cardiac phenomenon and whether these hearts should be excluded from
      transplantation.

PMID- 1394882
TI  - Restoration of cerebrovascular CO2 responsivity by glutamine synthesis inhibition
      in hyperammonemic rats.
AB  - Hyperammonemia increases brain glutamine levels, causes astrocytic swelling, and
      depresses cerebral blood flow (CBF) responsivity to CO2. Methionine sulfoximine
      (MSO) inhibition of glutamine synthetase activity, known to be enriched in
      astrocytes, prevents ammonia-induced increases in brain glutamine and water
      content. We tested the hypothesis that inhibition of glutamine accumulation
      restores CBF responsivity to CO2 during acute hyperammonemia. Pentobarbital
      anesthetized rats treated with either vehicle or MSO (150 mg/kg i.p.) received a
      6-hour intravenous infusion of either sodium or ammonium acetate. With subsequent
      induction of hypercapnia, CBF increased from 113 +/- 14 (mean +/- SEM) to 194 +/-
      9 ml/min per 100 g in control rats but was unchanged from 107 +/- 13 to 79 +/- 10
      ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic
      rats restored the CBF response to hypercapnia (from 73 +/- 8 to 141 +/- 14 ml/min
      per 100 g). With induction of hypocapnia, CBF decreased from 114 +/- 11 to 88 +/-
      11 ml/min per 100 g in control rats but increased from 112 +/- 13 to 142 +/- 19
      ml/min per 100 g in hyperammonemic rats. Treatment with MSO in hyperammonemic
      rats did not fully restore the response to hypocapnia but prevented the
      paradoxical increase in CBF (from 80 +/- 8 to 80 +/- 8 ml/min per 100 g). In
      control rats, MSO did not affect CO2 responsivity. Treatment with MSO prevented
      ammonia-induced increases in intracranial pressure. Hyposmotic-induced increases
      in brain water content and intracranial pressure attenuated the CBF response to
      hypercapnia but, unlike hyperammonemia, did not attenuate the response to
      hypocapnia. In contrast to hypercapnia, vasodilation in response to arterial
      hypotension was intact in hyperammonemic rats. We conclude that the grossly
      abnormal CBF responsivity to CO2 alterations during hyperammonemia is linked to
      glutamine accumulation rather than ammonia per se. Cerebral edema secondary to
      glutamine accumulation may contribute in part to abnormal CBF responses, although
      other aspects of astrocyte dysfunction are likely to be important.

PMID- 1394883
TI  - Cholinergically mediated tachyarrhythmias induced by a single extrastimulus in
      the isolated canine right atrium.
AB  - Cholinergic agonists and vagal stimulation potentiate the inducibility of atrial
      fibrillation. To describe the activation patterns and determine the mechanisms
      that sustain cholinergic fibrillation, tachyarrhythmias were induced with a
      single extrastimulus in the isolated Krebs-Henseleit-perfused canine right atrium
      (n = 11) at increasing concentrations of acetylcholine (from 10(-7.5) to 10(-4.5)
      M). Bipolar electrograms were recorded from 250 epicardial sites simultaneously
      during control conditions and during extrastimulation (S1S1, 300 msec; S1S2,
      effective refractory period+5 msec) with and without acetylcholine. Activation
      sequence maps were constructed from each recording. Without acetylcholine, no
      tachyarrhythmias were induced. With increasing concentrations of acetylcholine,
      the refractory period decreased, and nonsustained (< 2 seconds) rapid repetitive
      responses were induced. At higher concentrations, a sustained (> 2-minute)
      fibrillation was induced. Activation sequence maps revealed that the rapid
      repetitive responses were characterized by multiple reentrant circuits. The
      number of circuits and wavelets increased in a dose-dependent fashion. However,
      unexpectedly, this trend did not continue when the tachyarrhythmia became
      sustained. Instead, the reentry tended to stabilize to a small, single,
      relatively stable reentrant circuit. In conclusion, the data suggest that, in
      this model, below a critical level of refractory period (< 95 msec) atrial
      reentrant circuits, unassociated with anatomic obstacles, can become stable and
      dominate activation.

PMID- 1394884
TI  - Interferon-gamma and tumor necrosis factor synergize to induce nitric oxide
      production and inhibit mitochondrial respiration in vascular smooth muscle cells.
AB  - Nitric oxide (NO) is an important signal substance in cell-cell communication and
      can induce relaxation of blood vessels by activating guanylate cyclase in smooth
      muscle cells (SMCs). NO is synthesized from L-arginine by the enzyme NO synthase,
      which is present in endothelial cells. It was recently shown that SMCs may
      themselves produce NO or an NO-related compound. We have studied NO production
      and its effects on energy metabolism in cultured rat aortic smooth muscle cells.
      It was observed that the cytokines, interferon-gamma and tumor necrosis factor
      alpha, synergistically induced an arginine-dependent production of NO in these
      cells. This was associated with an inhibition of complex I (NADH: ubiquinone
      oxidoreductase) and complex II (succinate: ubiquinone oxidoreductase) activities
      of the mitochondrial respiratory chain, suggesting that NO blocks mitochondrial
      respiration in these cells. Lactate accumulated in the media of the cells,
      implying an increased anaerobic glycolysis, but there was no reduction of
      viability. An NO-dependent inhibition of mitochondrial respiration and a switch
      to anaerobic glycolysis would reduce energy production of the SMCs. This would in
      turn reduce the contractile capacity of the cell and might represent another NO
      dependent vasodilatory mechanism. It could be of particular importance in
      inflammation, since cytokines released by inflammatory cells may induce autocrine
      NO production in SMCs.

PMID- 1394885
TI  - [Studies on the strain differences of Schistosoma japonicum in the mainland of
      China. VII. Genetic variation and differentiation of five isolates].
AB  - Electrophoretic techniques have been used to survey five different field
      collected isolates (i.e., Anhui, Hubei, Guangxi, Sichuan and Yunnan) of S.
      japonicum from the mainland of China for genetic variation at 7 isozymes markers
      representing 9 loci. Polymorphic loci were observed for LDH-1, LDH-2, MDH and
      PGM, respectively, the proportion of polymorphic loci being 44.4%. Average
      heterozygosity varied between 0.223 and 0.425, with a mean of 0.332. Nei's
      genetic distance (D) among the populations of 5 isolates gave values between
      0.001 and 0.039 with an average of 0.023, indicating that these isolates are very
      closely related.

PMID- 1394886
TI  - [The activity of tumor necrosis factor in schistosomiasis japonica].
AB  - The activity of tumor necrosis factor (TNF) in both the culture supernatant of
      peripheral blood mononuclear cells (PBMC) and the serum was examined in 20
      patients of advanced schistosomiasis at 8th week after pyquiton treatment, and 6
      rabbits infected with S. japonicum cercariae at 8th and 16th weeks post-infection
      and using L929 cell cytotoxic assay. The results showed that the capacity of PBMC
      to produce TNF in response to LPS from patients with late schistosomiasis was
      significantly lower than that from normal subjects (P less than 0.01), whereas
      the activity of TNF in serum was significantly elevated (P less than 0.01). The
      capacity of PBMC to produce TNF and the TNF activity in serum of infected rabbits
      showed sharp rise at 8th week post-infection (P less than 0.01), and remained
      high at 16th week, then returned to normal level 8 weeks after treatment. The
      persistent rise of TNF in the circulation indicate that TNF might take part in
      the formation of hepatic fibrosis.

PMID- 1394887
TI  - [Study on toxicology of a new anthelmintic "85012"].
AB  - "85012", a new anthelmintic containing amidine synthesized in our laboratory, was
      experimentally effective against Nippostrongylus braziliensis and Ancylostoma
      caninum. In acute and subacute toxicity test, it was proved lowly toxic. There
      was no evidence that the drug induced any damages to main organs and tissues of
      animals. In order to evaluate its potential mutagenicity and teratogenicity,
      micronucleus test, bone marrow metaphase analysis, CHL cells chromosomal
      aberration assay, spermatic aberration test as well as teratogenicity test were
      performed. No mutagenic and teratogenic effects were observed.

PMID- 1394888
TI  - [Studies on the effect of immunoenhancing reagent "425" on egg granuloma
      formation in mice infected with Schistosoma japonicum].
AB  - Fourteen--34 days after Schistosoma japonicum-infected mice were injected
      intraperitoneally with immunoenhancing reagent, Chinese angelica root extract
      ("425"), the specific antibody (IgG) levels were significantly higher in Group
      III (362.67 +/- 162.21 - 480.00 +/- 289.45) than the control group (66.67 +/-
      39.68 - 245.33 +/- 101.56) in experiment one, and in Group II (488.00 +/- 320.38 
      768.00 +/- 267.38) than the control group (256.00 +/- 189.07 - 394.67 +/-
      141.06) in experiment two. The egg granulomatous formation were markedly
      diminished in the injected mice. The ratios of granulomas vs. eggs' mean
      diameters of Group III of mice were 5.24 +/- 1.04 - 3.95 +/- 0.77 and those of
      the control group were 6.59 +/- 1.19 - 5.29 +/- 0.94 in experiment one, those of
      the group II were 3.75 +/- 0.71 - 4.15 +/- 0.73 and those of the control group
      were 4.94 +/- 0.81 - 5.36 +/- 0.97 in experiment two. Meantime the egg antigen
      levels in the injected mice might be lower. This study shows that the control of
      immunomodulation of granulomatous formation in the hosts injected with
      immunoenhance reagent "425" can be induced.

PMID- 1394889
TI  - [Production and characterization of a murine protective monoclonal antibody
      against Schistosoma japonicum schistosomula].
AB  - Eight murine monoclonal antibodies against surface determinants of Schistosoma
      japonicum (Chinese mainland strain) schistosomula were generated, of which only
      one monoclonal IgM antibody (N15D9) gave protection at level ranging from 14 to
      39% in experiments of passive transfer or inhibition of infectivity while the
      others did not exhibit significant levels of passive protection. Further
      characterization of N15D9 antigen specificity showed that 96 and 14 kDa antigen
      molecules in cercaria, and 132 and 10 kDa in schistosomula could be recognized by
      N15D9 in Western blot assay. Furthermore, the 96 and 132 kDa molecules could also
      be recognized by pooled infected human sera while 14 kDa and 10 kDa only by sera
      from mice vaccinated with 3-hour schistosomula. The molecules recognizable by
      N15D9 were surface epitopes repeatedly expressed on cercaria, in vitro 3-hour
      mechanically transformed schistosomula and 5 day lung-stage schistosomula, as
      demonstrated by indirect immunofluorescence surface binding assay.

PMID- 1394890
TI  - [Generation and immunochemical characterization of an anti-egg monoclonal
      antibody specific to Schistosoma japonicum].
AB  - Monoclonal antibodies (McAbs) were generated from mice immunized with soluble egg
      antigen (SEA) of Schistosoma japonicum. Five of which were specific to SEA of S.
      japonicum. The isotype of these McAbs was IgG1. Immunoblotting showed that the
      approximate molecule weight of the antigens recognized by the McAbs were 22 kDa,
      116 kDa and greater than 200 kDa respectively. At least 3 isomorphs of the 22 kDa
      antigen recognized by 1E1 were found at pI 4.6-6 with 2-D Western blot. Moreover,
      immunoprecipitation using 125I-labeled S. japonicum SEA demonstrated that only
      one band corresponding to 30 kDa was recognized by 1E1.

PMID- 1394891
TI  - [Localization of the antigen in erythrocytic stages of Plasmodium yoelii by
      immuno-electron microscopy].
AB  - In this study, the antigen recognized by the protective McAb M26-32 in
      erythrocytic stages of P. yoelii was localized by immuno-electron microscopy with
      LR Whithe resin embedding and colloidal gold probe cytochemical techniques. The
      results indicated that the antigen which reacts specifically to McAb M26-32 was
      mainly localized within the cytoplasm of early and late trophozoites, schizonts
      and merozoites, being the common antigen of asexual blood stages of the
      plasmodium. The amount of the antigen was on the increase during the development
      of trophozoite, while a portion of the antigen might be transported outward by
      exocytosis of the parasites and then be localized in the cytoplasm of the
      infected erythrocytes adjacent to the parasites.

PMID- 1394892
TI  - [Roles of T cell subsets in the protective immunity of mice against Plasmodium
      yoelii].
AB  - BALB/c mice which had developed protective immunity against Plasmodium yoelii (P.
      y.) challenge were injected with anti-CD4 or anti-CD8 monoclonal antibody, and
      were then challenged again with P. yoelli. No impairment of protection was
      observed. CD8+T cells obtained from spleens of these mice were transferred to
      BALB/c nude mice and induced partial protection, while transfer of CD4+T cells
      did not so. In P. yoelli-mouse model, the parasites invaded reticulocytes in the
      early infection, and the infected reticulocytes could be recognized and attacked
      by sensitized CD8+T cells. In late infection when P. yoelli also invaded mature
      erythrocytes, the protective effect of CD8+T cells decreased and the main role of
      protection was played by antibodies.

PMID- 1394893
TI  - [In vitro development of sodium artesunate resistance in Plasmodium falciparum].
AB  - Plasmodium falciparum (Lab. culture FCR3 isolate) developed resistance to sodium
      artesunate after exposure to the drug in vitro. The drug effective concentration
      which resulted in 50 per cent schizont maturation inhibition (IC50) was 1.6 ng/ml
      (4.1 nmol/L) before exposure to the drug. After 130 days of discontiguous
      exposure to sodium artesunate in a stepwise fashion, the sensitivity of the
      isolate to the drug decreased, with its IC50 3-fold higher than that of the
      parent isolate. The resistance to artesunate decreased significantly after the
      resistant line was grown in drug-free medium.

PMID- 1394894
TI  - [Study on localization of cystic fluid antigen of Cysticercus cellulosae using
      McAb-IGSS].
AB  - A study was undertaken on the localization of specific combination of McAb
      against cystic fluid antigen of Cysticercus cellulosae by immunogold silver
      staining method (IGSS). It was shown that the combination sites of McAb F3 were
      distinct in the frozen and paraffin sections of Cysticercus cellulosae. The black
      granules in the bladder walls presented double-layer distribution and those in
      the scolex folded sites concentrated into pieces. The combination sites of McAb
      labeled by IGSS against cystic fluid antigen of Cysticercus cellulosae were
      consistent with the distribution of the cell layers of Cysticercus cellulosae.
      The sections in the control group had scarce and irregular distribution, which
      could be differentiated distinctly from those in the experimental group.

PMID- 1394895
TI  - [An electrophoretic karyotype of Acanthamoeba polyphaga].
AB  - An electrophoretic karyotype of Acanthamoeba polyphaga has been preliminarily
      analysed by means of pulse field gel electrophoresis (PFGE). Ten chromosomal DNA
      bands are distinguishable on the gel. Using yeast (Saccharomyces cerevisiae)
      chromosomal DNA as size standard, we estimate the size of the chromosomes to be
      between about 200 kilobase pairs (kb) and 2 megabase pairs (mb).

PMID- 1394896
TI  - [Comparative analysis of amino acids of metacercaria and larvae of diploid and
      triploid of Paragonimus westermani].
AB  - The diploid type of Paragonimus westermani in Heilongjiang Province and triploid
      type of P. westermani in Liaoning Province were examined for amino acids by high
      performance liquid chromatography (HPLC). Eleven kinds of amino-acids of diploid
      type and 15 kinds of triploid type were found in metacercaria; 15 kinds amino
      acids of diploid type and 16 kinds of triploid type were detected in larvae. The
      amino acids were more abundant in larvae than in metacercaria and more in the
      triploid than in the diploid type. The predominant amino acids were cystine and
      glutamic acid.

PMID- 1394897
TI  - [Transmission electron microscopy of tegument and digestive tract of Schistosoma
      japonicum during long-term cultivation in vitro].
AB  - The article reports the result of the observation on the ultrastructure of the
      tegument and digestive tract of Schistosoma japonicum schistosomula cultured 130
      days in vitro in 841 medium, and the 42-day-old adults from infected animal
      cultured 23 days in 851 medium by transmission electron microscopy. The results
      showed that the ultrastructure of the tegument including sensory papillae and
      flame cells was normal. The matrix seemed to have no vacuolization. The surface
      of the esophagus was highly rugous. Many laminae and lipid droplets filled the
      lumen of the digestive tract and the tubules-like depressions from basal lamina
      were occurred. All these structures seemed to have less variation as compared
      with the prior authors' data from normal worms. It is considered that the above
      two media which we cesigned were suitable for the growth and development of the
      schistosomes due to the tegument and digestive tract maintained their metabolic
      function in the long-term cultivation in vitro. (Figs 1-10).

PMID- 1394898
TI  - [Study on free amino acids and protein in hemolymph of Anopheles stephensi].
AB  - The changes in the contents of free amino acids in hemolymph of Anopheles
      stephensi were determined by automatic amino acid analyzer. The changes in
      hemolymph protein were determined by ultraviolet absorption method. Free amino
      acids in hemolymph of infected mosquitoes were compared with those in noninfected
      mosquitoes. At 4 days after blood meal, 6 kinds of amino acids decreased
      markedly, and 5 kinds of amino acids increased markedly; at 7 days after blood
      meal, 4 kinds of amino decreased markedly, while 7 kinds of amino acids increased
      markedly; at 11 days after acids blood meal, 9 kinds of amino acids decreased
      markedly, and 4 kinds of amino acids increased remarkably. The protein
      concentration of infected mosquitoes was higher than that of noninfected ones.

PMID- 1394899
TI  - [Studies on negative conversion of schistosome-infected snails in mountainous
      region of Yunnan].
AB  - The monthly cercaria shedding of 90 artificially infected Oncomelania snails was
      observed under a field condition in mountainous region, Shitoudi Village, Weishan
      County, Yunnan Province. The results showed that 20% of teh snails shed cercaria
      monthly, 42.2% could shed irregularly and 37.8% stopped releasing cercariae after
      several times of shedding. Final direction of the snails showed that none
      cercaria or sporocyst could be found in part of the snails. A total of 304
      naturally infected snails were observed individually every month. Samples were
      taken each month from the snails which did not shed cercaria, then dissected and
      examined. The negative conversion rate was calculated in the second, third,
      fourth, fifth and sixth month after the first shedding, which were 36.1, 50.0,
      41.0, 39.8 and 2.6% respectively.

PMID- 1394900
TI  - [Changes in T lymphocytes and their subpopulations and IgG in peripheral blood
      from mice infected with Trichinella spiralis].
AB  - Acid alpha-naphthyl esterase (ANAE), a cytoplasmic marker, was used to identify
      the T lymphocytes and their subpopulations in peripheral blood of mice infected
      with Trichinella spiralis, and Dot-ELISA was used to identify the serum IgG
      antibody of the infected mice. The results showed that T lymphocytes increased on
      the d3 after infection, reaching the peak on d14, and then remained in number
      greater than normal up to d77. The spotted granular ANAE positive cells (Help T
      cells, Th) decreased and the scattered granular ANAE positive cells (Suppressor T
      cells, Ts) increased, leading to a drop of the Th/Ts ratio. The reduction in host
      immune function during T. spiralis infection might be related to the drop of
      Th/Ts ratio. At the same time, the serum IgG antibody increased on d7 after
      infection, reaching the peak on d28, and remained higher up to d140. The results
      indicated that the host's cellular immunological level was lower while the host's
      IgG antibody level was higher during T. spiralis infection.

PMID- 1394901
TI  - [Analysis of newborn larva of Trichinella spiralis by immunoblot].
AB  - Newborn larva (NBL) antigens of Trichinella spiralis were analysed by Immunoblot,
      and were compared with the adult and muscle larva antigens. The SDS-PAGE patterns
      of NBL somatic constituents consisted of about 40 polypeptide bands, which were
      obviously different from those of adult and muscle larva. Immunoblot analysis
      indicated that immunization with NBL could induce a stage specific immune
      response. The molecular weight of specific NBL antigens were 129, 120, 89, 87,
      79, 74, 72, 64, 58, 43, 40, 38, 34, 32, and 20kDa. But during the natural course
      of the infection, we could not detect the antibodies of anti-NBL in the host.

PMID- 1394902
TI  - [The dynamics of antigen and antibody in Schistosoma japonicum egg granuloma and
      its relationship with the granuloma response].
AB  - Synchronous Schistosoma japonicum egg granuloma in the lung of mouse model and
      PAP (peroxidas-anti-peroxidase) technique were employed to study the dynamics of
      antigen and antibody in the egg granuloma of S. japouicum and its relationship
      with the granuloma formation. The granulomatous response began on the 3.5 day
      after egg injection and increased to the maximal size at the 4th week. Lymphocyte
      populations and macrophage comprised an important part of lesions during the time
      of acute granulomatous response (7-28 day). Using PAP staining, the SEA within
      egg could be detected at high level on the first day after egg injection and then
      declined gradually. On the contrary, the SEA around egg was minimal at the first
      week and increased to the peak at the 4th week, then decreased gradually. No
      antibody could be detected throughout the experimental period (35 days). The
      results suggested that 1) the antigen of Schistosoma egg is the essential factor
      for the granuloma formation. 2) S. japonicum egg granuloma could be formed in
      unsensitized mouse. 3) The mechanism of egg granuloma formation of S. japonicum
      is similar to that of S. mansoni.

PMID- 1394903
TI  - [Epidemiological trend in late stage of control in Malayan filariasis endemic
      areas with Anopheles anthropophagus as main vector].
AB  - During 1982-1990, a longitudinal observation on prevalence trend of malayan
      filariasis has been made in endemic areas with An. anthropophagus as the main
      vector. A total of 22,795 person-times of blood examination were made, and 30,439
      An. anthropophagus and 10,061 An. sinensis were dissected respectively. The
      microfilaraemia rate dropped from 1.0% to 0.14%, and the infection rate of An.
      anthropophagus decreased from 0.74% to 0.09% in 3 endemic villages, while no
      positive case or infected vector occurred in 5 villages where microfilaraemia
      cases were absent since the beginning of the study. In a cross-sectional survey,
      855 villages of 17 counties has been monitored for 10 years. Out of 213,934
      person-times of blood examination, only 56 were positive, the average
      microfilaraemia rate being 0.0262%, and 94.64% of the positive had already been
      detected before 1986. Based on these data, it has been suggested that in endemic
      areas with An. anthropophagus as main vector, when the microfilaraemia rate
      dropped to less than 1% after control, there was no indication that the rate
      would upgrade during the survey period. A decline trend of the transmission of
      malayan filariasis, therefore, has been exhibited.

PMID- 1394904
TI  - [Studies on the strain differences of Schistosoma japonicum in the mainland of
      China. VIII. Immunoreactions in experimental animals].
AB  - Observations on the immunoreactivities toward egg antigens of different
      experimental animals infected with Schistosoma japonicum were made, which
      included mouse, rat, hamster, rabbit and rhesus monkey. The cercariae applied for
      infection were shed by snails collected from 5 different isolates, i.e., Anhui,
      Hubei, Sichuan, Yunnan and Guangxi in the mainland of China. Sera from the same
      sort of animals were separately pooled according to the different sources of
      infection mentioned above. Antibody reactivities were evaluated by COPT, LAT and
      ELISA. In COPT each serum sample was tested with ova from homologous and
      heterologous isolates, whereas soluble egg antigen merely prepared from Anhui
      isolate was used in LAT and ELISA. The level of antibodies detected by homologous
      or heterologous worm isolate antigens was compared. The results suggested that
      the positive antibody detection rate might not be influenced by antigens prepared
      from S. japonicum eggs of different isolates in the mainland of China.

PMID- 1394905
TI  - [Morphological and taxonomical studies on anisakidae larvae found in marine
      fishes of China. II. Gulf of Tong King].
AB  - A survey on Anisakidae larvae in 29 species (134 specimens) of marine fishes in
      the Gulf of Tong King has been carried out. Anisakidae larvae were detected in 15
      out of 29 species. The detected specimens were identified as larvae of Anisakis
      simplex, Hysterothylacium and Pseudoterranova. The parasitization rate of
      Anisakis simplex larvae, the main pathogen of anisakiasis, in fishes was 30.6%
      (41/134), while the parasitization rates of Hysterothylacium and Pseudoterranova
      larvae were comparatively low. Hysterothylacium larvae China type I detected from
      Muraenesox cinereus and Trichiurus haumela was a new record. Their morphological
      characteristics were summarized as follows: 1. Length 10.78-14.18 mm, Width 0.25
      0.38 mm, the length of the esophagus is 1.14-1.73 mm, intestinal cecum 0.77-1.24
      mm and ventricular appendage 6.27-8.40 mm, extending parallelly with the
      intestine to the last quarter of the larva; 2. Boring tooth was present, but
      mucron was absent; 3. No genital anlage was observed.

PMID- 1394906
TI  - [Oxidative phosphorylation of liver mitochondria in Oncomelania snail].
AB  - Oxidative phosphorylation of liver mitochondria in Oncomelania snail was
      separately detected by using oxygen electrode and spectrophotometer. ADP
      increased oxidative reaction of liver mitochondria from 0.187 to 0.318 mumol
      O2/mg protein.20 min. When certain substrates of citric acid cycle were added to
      liver mitochondria of Oncomelania snail, we found that oxidative phosphorylation
      increased to 0.353-0.444 mumol O2/mg protein.20 min. ATPase was detected in the
      liver of Oncomelania snail. The oxidative phosphorylation of mitochondria in
      Oncomelania snail could be markedly inhibited by DNP and molluscicide
      bromoacetamide, but the latter didn't show the inhibition of ATPase. (Figs. 1,2).

PMID- 1394907
TI  - [Ultrastructure of erythrocytic stage of Plasmodium vivax in humans].
AB  - After the merozoite entered the erythrocyte, the membrane debris in the
      parasitophorous vacuoles of early ring form was passed out through a narrow
      external aperture in erythrocyte to the exterior. The trophozoite was oval or
      irregular in shape. Ingestion of host cell cytoplasm occurred cystostomally. The
      asexual parasite possessed cristate mitochondria and was surrounded by a single
      membraned pellicle. The gametocyte possessed cristate mitochondria and was
      surrounded by two unit membranes. The cytoplasm of mature macrogametocytes
      contained many ribosomes, mitochondria and osmiophilic bodies and a small nucleus
      while microgametocytes contained fewer ribosomes, osmiophilic bodies and
      mitochondria and a large nucleus. Three characteristic morphological alterations
      were observed within the host cells, that is, small vesicles, cytoplasmic cleft
      and caveola-vesicle complex. The clefts within the cytoplasm of the host
      erythrocytes were present in all human malarial parasites. The small vesicles
      distributed all over the cytoplasm were surrounded by a unit membrane. The
      caveola-vesicle complex consisted of caveolae was surrounded by small vesicles
      and probably corresponds to a Schuffner's dot. (Figs. 1-13).

PMID- 1394908
TI  - [The blood schizontocidal effects of pyronaridine, amodiaquine, mefloquine and
      qinghaosu on mice infected with Plasmodium berghei].
AB  - The asexual stages of P. berghei ANKA were completely eliminated as revealed in a
      "4-day suppressive test" with the daily dose of pyronaridine 12.5 mg base/kg or
      amodiaquine 25 mg base/kg. Mefloquine 25 mg base/kg and qinghaosu 100 mg/kg
      though exerted obvious suppressive effect, the cure rates were only 50% and 0%,
      respectively. In treating chloroquine-sensitive P. berghei ANKA strain
      pyronaridine exhibited the best therapeutic activity, which was followed by
      amodiaquine, mefloquine and quinghaosu. In treating moderately chloroquine
      resistant P. berghei NS line the cure rate of pyronaridine 12.5 mg/kg.d x 4 was
      70%, but none of the 10 infected mice from any group was cured by amodiaquine 100
      mg/kg.d, mefloquine 100 mg/kg.d or qinghaosu 200 mg/kg.d. Though the latter 3
      drugs showed prominent suppressive effects, parasitemia remained positive or
      recrudesced after dosing. We demonstrate that parasites resistant to chloroquine
      had cross resistance to amodiaquine, mefloquine and inghaosu at various degrees.
      Amodiaquine 100 mg/kg.d, mefloquine 100 mg/kg.d and qinghaosu 200 mg/kg.d
      exhibited no obvious suppressive activity on highly pyronaridine-resistant line
      of P. berghei, indicating the existence of cross resistance to pyronaridine.

PMID- 1394909
TI  - [Observation of ultrastructure and drug sensitivity of in vitro cultured
      exoerythrocytic form of Plasmodium berghei].
AB  - The ultrastructure of in vitro cultured exoerythrocytic stage (EE) of Plasmodium
      berghei (P. b.) was observed under transmission electron microscope (TEM). The
      drug sensitivity of EE was also measured in vitro. The EE was cultured in
      monolayer host cell, fixed and embedded in situ. The ultrathin sections were
      prepared and examined by routine methods. The TEM pictures showed that the fine
      structure of in vitro cultured EE was similar with that of EE grown in rat
      hepatocytes in vivo, as described by Meis et al. The parasite was found within a
      parasitophorous vacuole, with nucleus, mitochondria, endoplasmic reticula and
      Golgi apparatus were observed inside the parasite. After 24 h cultivation, the EE
      was incubated for 48 h in medium containing a serial concentrations of primaquine
      or chloroquine, then examined under light microscope. The percentage of abnormal
      parasites was calculated. The preliminary results showed that the sensitivity of
      cultured P. b. EE to primaquine and chloroquine was significantly different. At
      the same concentration of 1 x 10(-5) mol/L, the percentage of abnormal parasites
      was 38.5 +/- 3.9% and 5.7 +/- 1.9%, respectively. These results demonstrated that
      the in vitro cultivation system of P. b. EE would have potential utility in
      antimalarial drug research. (Figs. 1-6).

PMID- 1394910
TI  - [The first record of human natural infection of Echinochasmus liliputanus].
AB  - Human natural infection with Echinochasmus liliputanus was found for the first
      time from the inhabitants of Hexian county of Anhui Province in Spring, 1991.
      Sixty worms collected from 3 infected persons were studied morphologically. The
      adult worms are leaf-shaped, 1519.4-2056.3 x 466.4-564.0 microns in size. The
      width of the collar is 235.8-297.3 microns. A row of 24 collar spines with size
      of 22.5-35.6 x 8.8-10.6 microns is arranged on the collar symmetrically with
      dorsal and ventral interruption. The oral sucker is terminal, 107.6-148.6 x 102.5
      148.6 microns. The length of the prepharynx is 25.6-66.7 microns, the pharynx,
      97.3-127.8 microns and the oesophagus 117.9-205.0 microns. The caeca 764.3
      1,248.8 x 21.0-39.0 microns extends to the distal end of the body. The acetabulum
      is anterior to the middle level of the body, 205.0-240.9 x 205.0-235.8 microns in
      size. Two testes, situated in the posterior one third of the body, is slightly
      oval, in tandem; the anterior one is 133.3-199.9 x 199.9-256.4 microns in size,
      and the posterior one, 178.9-251.3 x 164.0-246.0 microns. The Cirrus pouch is
      kidney-shaped, 211.5-248.5 x 112.8-194.8 microns in size, located between the
      bifurcation of the intestine and the acetabulum, containing the seminal vesicle
      and cirrus. The ovary is oval in shape, 71.8-92.3 x 76.8-97.4 microns in size,
      situated in the middle of the body. The vitellaria are distributed on each side
      from the acetabulum to subterminal, consisting of many follicles. The uterus is
      short, convoluted between the anterior testis and the acetabulum, containing 0-6
      eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394911
TI  - [Preparation and identification of anti-Trichomonas vaginalis monoclonal
      antibodies].
AB  - Hybridomas producing monoclonal antibodies (McAb) directed against Trichomonas
      vaginalis have been produced by fusing NSI myeloma cells with spleen cells of
      BALB/c mice immunized with Trichomonas vaginalis. IFA technique was used to test
      the binding activity of four McAbs produced. The McAb belonged to the IgG
      subtypes IgG1 (2A2, 2A4 McAb), IgG3 (2H9 McAb) and IgG 2b (2A12 McAb). Three
      McAbs, designated 2A2, 2A4, 2A12, reacted with a surface membrane component of
      live Trichomonas vaginalis. One (2A12) of them produced complement-dependent
      cytolysis of the parasites. Others (2A2,2A4) produced complement-independent
      cytotoxicity of the parasites. 2H9 McAb which reacted with the nucleus of the
      organisms did not agglutinate the parasites. The four McAbs which did not have
      cross reaction with some protozoa of Zoomastigophorea species were specific
      antibodies against Trichomonas vaginalis. (Figs. 1-3).

PMID- 1394912
TI  - [Application of chromatographic technique in parasitological research].

PMID- 1394913
TI  - [Chemical synthesis and cloning of Plasmodium falciparum 45 peptide antigen
      gene].
AB  - We have synthesized a 162 bp gene of human Plasmodium falciparum hybrid peptide
      antigen by the solid-phase phosphoramidite method with ABI 381A DNA synthesizer.
      The gene encodes three fragments of the relative molecules 83 kDa, 55 kDa and 35
      kDa merozoite-specific proteins and two CS repeats or four peptides. The gene
      with the designed two cohesive ends was divided into 8 fragments to be
      synthesized. All synthetic fragments were annealed and ligated with T4 DNA ligase
      to form double DNA chain. This synthetic gene was recombined with P-Blue script
      as vector and transformed into E. coli JM109. The positive recombinants were
      screened out by dot hybridization and enzyme analysis. The DNA sequence analysis
      showed that the synthesized human Plasmodium falciparum hybrid peptide antigen
      gene was identical with the designed one. (Figs. 1-4).

PMID- 1394914
TI  - [Isolation of germinal cells from the secondary cysts of Echinococcus granulosus
      harbored in mice].
AB  - The secondary cyst tissues derived from mice infected with protoscoleces of
      Echinococcus granulosus for 8-10 months were digested with 0.25% trypsin at 37
      degrees C for 30 min. The separation of different cells in the remaining
      suspension was achieved by discontinuous gradient centrifugation. The germinal
      cells were washed 3 times with ice-cold HBSS, and then cultivated in the medium
      of RPMI 1640 supplemented with 20% of calf serum. The cells were kept in an
      incubator at 37 degrees C in an atmosphere of 95% air-5% CO2. After incubation
      for 5-7 days, the germinal cells began to multiply accompanied by the enlargement
      of cells as compared with those before incubation. The surface of both isolated
      and/or cultured cells showed smooth appearance examined by scanning electron
      microscopy. Immunofluorescence assay and enzyme-linked immunosorbent assay had
      been used for examining the specific antigenicity of the cells. The results
      showed that antigen components of E. granulosus were detected either on cell
      surface or in soluble proteins of the cells. Furthermore, 120 NIH female mice
      were inoculated intraperitoneally with 1-5 x 10(7) cultured germinal cells and
      sacrificed 1-3 months after inoculation. Only 2 cystic materials had been
      detected in two mice. Of which, one located in the liver and the other in
      peritoneal cavity of the animals. Histological examination noted that the cystic
      materials consisted of germinal layer and cyst fluid, but no laminated layer was
      observed. The above mentioned evidence demonstrated that the cells isolated from
      the cysts of E. granulosus were germinal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394915
TI  - [DNA sequence of surface antigen gene gp195 of two Chinese isolates of Plasmodium
      falciparum from Hainan].
AB  - Amplification of DNA sequence of surface antigen gene, block II of gp195 from 2
      Chinese isolates of Plasmodium falciparum FCC 7801/HN B3 and FCC M21/HN from
      Hainan, China, was established by using the polymerase chain reaction. A
      comparison of the 154 peptide sequences of the 2 Chinese isolates showed that
      they were identical, but there was a difference of 10 peptides among the
      established 154 peptides between the two Chinese isolates and MAD 20 (a Papua New
      Guinea isolate). The need to determine the fragments having protective effect
      against malarial infection, and to study the genetic basis of the antigen
      polymorphism of Chinese strains of Plasmodium falciparum is evident.

PMID- 1394916
TI  - [Treatment of soil-transmitted helminth infections by anthelmintics in current
      use].
AB  - The efficacy of broad-spectrum anthelmintics in current use was studied in
      Hengshan County, Hunan Province. The vermicides under study include albendazole
      (400mg, single dose), mebendazole composite (mebendazole 100 mg and levamisole
      25mg bid x 3d), oxantel pyrantel pamoate composite (pyrantel pamoate 150 mg and
      oxantel pamoate 150 mg bid x 2d), and pyrantel pamoate composite (base 10 mg/kg,
      single dose). Therapeutic effect assessed 2 weeks after medication revealed
      Ascaris egg negative rates or cure rates (CR) of 97.5-100% for the former 3
      regimens, and 80.9% for the latter one; while CR for hookworm infection were
      95.4%, 78.6-100%, 96.7% and 83.3%, respectively. A follow-up survey pursued 4
      weeks post treatment showed no significant difference in CR for the above
      regimens. Judging from CR in Trichuris trichiura infection, pyrantel pamoate
      composite was recommended as the drug of choice (89.3%), which was followed by
      mebendazole composite (64.6-83.8%) and albendazole (28.2-42.6%), whereas pyrantel
      pamoate was inefficacious. Obvious egg reduction rates were evidenced post
      application of the above drugs in trichuriasis treatment except pyrantel pamoate
      at single dose.

PMID- 1394917
TI  - Neurohormonal inhibition and hemodynamic unloading during prolonged inhibition of
      ANF degradation in patients with severe chronic heart failure.
AB  - BACKGROUND: The purpose of this study was to investigate the therapeutic
      potential of prolonged inhibition of atrial natriuretic factor (ANF) degradation
      in patients with severe chronic heart failure. METHODS AND RESULTS: The effects
      of repeated doses of the endopeptidase inhibitor candoxatrilat (150 mg i.v.) were
      examined over a 24-hour period in patients with severe chronic heart failure (New
      York Heart Association class III-IV). Plasma alpha-hANF(99-126) was elevated at
      baseline (235 +/- 59 pg/ml), increased 2.5-fold at 2 hours after the first dose,
      and remained significantly elevated throughout the 24-hour protocol. In contrast,
      pro-hANF(31-67) decreased from 3,151 +/- 616 to 2,072 +/- 362 pg/ml (p less than
      0.05). Cardiac index (CI) increased only transiently after the first dose of
      candoxatrilat (CI, 2.11 +/- 0.2 to 2.67 +/- 0.28 l/min/m2, p less than 0.05).
      Sodium excretion increased sixfold (p less than 0.05) 2 hours after the first
      dose of candoxatrilat and remained significantly elevated throughout the
      protocol. Degree of natriuresis and diuresis in response to candoxatrilat was
      closely related to baseline cardiac output. Glomerular filtration rate and volume
      excretion did not change significantly. Pulmonary capillary wedge pressure fell
      from 23 +/- 3 to 18 +/- 3 mm Hg (p less than 0.05) and remained below baseline
      throughout the 24 hours. Arterial pressure, heart rate, and total peripheral
      resistance did not change significantly during the 24-hour period. Urinary cGMP
      excretion increased fivefold (p less than 0.05), whereas urinary ANF
      immunoreactivity and plasma cGMP levels remained unchanged. Excretion of
      prostacyclin metabolite 6-keto-PGF-1 alpha increased 3.3-fold (p less than 0.05).
      Plasma norepinephrine and epinephrine levels decreased significantly after
      candoxatrilat and remained suppressed over the 24-hour period. There was also a
      transient reduction in plasma vasopressin, aldosterone levels, and plasma renin
      activity. Hematocrit, total protein content, and plasma albumin concentrations
      did not change, indicating that no fluid shift into the extravascular space had
      occurred. CONCLUSIONS: 1) The inhibition of ANF degradation causes sustained drop
      in left and right atrial pressures that appears to be mediated by an inhibition
      of neurohumoral activity; 2) concomitant inhibition of bradykinin breakdown
      (which in turn stimulates renal prostacyclin synthesis) contributes to
      natriuresis; 3) the close correlation between renal response and baseline cardiac
      index indicates that an inadequate renal perfusion secondary to low cardiac
      output diminishes the efficacy of this treatment modality. This spectrum of
      action would be advantageous for a first-line diuretic agent early in the course
      of disease rather than in patients with advanced chronic heart failure.

PMID- 1394918
TI  - Sex-associated differences in left ventricular function in aortic stenosis of the
      elderly.
AB  - BACKGROUND: In aortic stenosis, the response of the left ventricle to pressure
      overload varies from compensated hypertrophy to overt heart failure. The
      determinants of left ventricular adaptation are poorly understood. METHODS AND
      RESULTS: Left ventricular function was compared to assess the role of sex in 34
      women and 29 men 60 years or older with both hemodynamic and echocardiographic
      data characteristic of severe aortic stenosis and no important coronary artery
      disease. Despite a similar degree of left ventricular outflow obstruction in
      women versus men (aortic valve area 0.54 +/- 0.20 versus 0.59 +/- 0.19 cm2, NS),
      the left ventricle of women had a greater fractional shortening (37 +/- 12 versus
      25 +/- 12%, p = 0.001), achieved a smaller end-systolic chamber size (1.82 +/-
      0.64 versus 2.17 +/- 0.65 cm/m2, p = 0.04), and generated more pressure (210 +/-
      35 versus 182 +/- 29 mm Hg, p = 0.001) with a greater maximum positive dP/dt
      (2.153 +/- 794 versus 1,595 +/- 384 mm Hg/sec, p = 0.02). The men had a lower
      cardiac index (2.12 +/- 0.59 versus 2.49 +/- 0.63 l/min/m2, p = 0.02), higher
      mean pulmonary artery pressure (35 +/- 13 versus 27 +/- 10 mm Hg, p = 0.01), and
      shorter ejection period (340 +/- 40 versus 370 +/- 40 msec, p = 0.02). Women and
      men were equally symptomatic. Supernormal left ventricular ejection performance
      was present in 41% of the women and only 14% of the men (p = 0.002). This
      subgroup of women had a small, thick-walled chamber (end-diastolic radius to
      thickness ratio, 1.58 +/- 0.52 versus 2.45 +/- 0.51 in control women, p = 0.01)
      with low end-systolic wall stress. Subnormal ejection performance was present in
      64% of the men and only 18% of the women (p = 0.002). This subgroup of men had an
      increased chamber size and high end-systolic wall stress compared with control
      men. Greater left ventricular mass was present in men compared with women (211 +/
      55 versus 179 +/- 55 g/m2, p = 0.03). CONCLUSIONS: Sex is a factor in left
      ventricular adaptation to valvular aortic stenosis in adults 60 years or older.

PMID- 1394919
TI  - Detection of unique transmural architecture of human idiopathic cardiomyopathy by
      ultrasonic tissue characterization.
AB  - BACKGROUND: Noninvasive approaches to the evaluation of idiopathic cardiomyopathy
      are limited. Recent work from our laboratory has used quantitative ultrasound to
      define the three-dimensional structure of normal human myocardium and the
      myocardial remodeling associated with infarction. Our goal was to define the role
      of ultrasonic tissue characterization for detection of specific alterations in
      the three-dimensional transmural architecture of idiopathic dilated
      cardiomyopathy. METHODS AND RESULTS: We measured frequency-dependent backscatter
      from 22 cylindrical biopsy specimens from nine explanted fixed hearts of patients
      who underwent heart transplantation for idiopathic cardiomyopathy, seven
      specimens from normal portions, and 12 specimens of infarcted tissue from six
      explanted fixed human hearts. Consecutive transmural levels from each specimen
      were insonified with a 5-MHz broadband transducer. The dependence of apparent
      (uncompensated for attenuation) backscatter, B(f), on frequency (f) was computed
      from radiofrequency (rf) data as: magnitude of B(f)2 = afn, where n is an index
      that reflects in part the size of the dominant scatterers in myocardial tissue.
      Myofiber diameter and percentage fibrosis were determined at each transmural
      level for each specimen. For cardiomyopathic tissue, the frequency dependence of
      backscatter (n) increased progressively from epicardial to endocardial (0.02 +/-
      0.37 to 1.01 +/- 0.12, p less than 0.05) levels in conjunction with a progressive
      decrease in myofiber diameter (29.5 +/- 0.9 to 21.4 +/- 0.6 microns, p less than
      0.0001). In contrast, in tissue from areas of infarction, the frequency
      dependence decreased progressively from epicardium to endocardium (0.91 +/- 0.20
      to 0.23 +/- 0.21, p less than 0.05) in conjunction with a progressive increase in
      the percentage of fibrosis (23.5 +/- 9.4% to 54.5 +/- 4.9%, p less than 0.005).
      Normal tissue exhibited no significant transmural trend for frequency dependence,
      myofiber diameter, or percentage fibrosis. CONCLUSIONS: These data indicate the
      presence of a heterogenous transmural distribution of scattering structures
      associated with human idiopathic cardiomyopathy and myocardial infarction that
      may be detected by ultrasonic tissue characterization. The divergence of these
      transmural trends for frequency dependence of backscatter reflects distinct
      mechanisms of structural heterogeneity for different pathological processes that
      comprise a transmural gradation of cell size and fibrosis for idiopathic
      cardiomyopathy and infarction, respectively.

PMID- 1394920
TI  - Regional left ventricular wall thickening. Relation to regional uptake of
      18fluorodeoxyglucose and 201Tl in patients with chronic coronary artery disease
      and left ventricular dysfunction.
AB  - BACKGROUND: In previous studies comparing regional 201Tl (201Tl) and
      18fluorodeoxyglucose (FDG) activity in patients with chronic coronary artery
      disease and left ventricular dysfunction, we hypothesized that regions with mild
      to-moderate reduction in FDG activity and regions with mild-to-moderate
      irreversible 201Tl defects after 3- to 4-hour redistribution represent viable
      myocardium. In the present study, regional FDG and 201Tl activities were compared
      with regional systolic wall thickening by gated magnetic resonance imaging (MRI)
      to confirm the presence of viable myocardium in these territories. METHODS AND
      RESULTS: Twenty-five patients with chronic stable coronary artery disease and
      left ventricular dysfunction (ejection fraction, 28 +/- 10) underwent exercise
      201Tl tomographic imaging (SPECT), using a reinjection protocol, positron
      emission tomography (PET) with FDG and H2(15)O, and gated MRI. Matched SPECT,
      PET, and MRI tomograms were analyzed. From the PET data, 105 regions had matched
      reduction in FDG and blood flow, of which 69 regions had moderately reduced FDG
      uptake (50-79% uptake relative to a normal reference region) and 36 had severely
      reduced FDG uptake (less than 50% of normal activity). Regions with moderately
      reduced as compared with severely reduced FDG activity had greater end-diastolic
      wall thickness (9.4 +/- 2.6 versus 8.0 +/- 3.7 mm; p less than 0.05) and regional
      systolic wall thickening (1.7 +/- 2.7 versus -0.7 +/- 2.1 mm; p less than 0.01).
      From the SPECT data, 169 irreversible 201Tl defects after 3-4 hour redistribution
      were identified, of which 70 were mild (greater than 65 to less than 85% of
      maximal 201Tl activity), 52 were moderate (50-65% of maximal activity), and 47
      were severe (less than 50% of maximal activity). Regional systolic wall
      thickening was greater in regions with normal 201Tl uptake (3.3 +/- 2.3 mm) as
      compared with all other regions. Regions showing only mild or moderate
      irreversible defects at redistribution, however, showed wall thickening (2.4 +/-
      2.4 and 2.2 +/- 2.5 mm, respectively), which was similar to that observed in
      regions with reversible 201Tl defects (2.1 +/- 2.2 mm). Only regions with severe
      irreversible defects at redistribution showed absence of thickening (-0.1 +/- 2.9
      mm, p less than 0.01 versus all other groups). After 201Tl reinjection, 12 of 47
      (26%) regions with severe irreversible defects showed enhanced 201Tl uptake. The
      impairment in regional systolic wall thickening was not significantly different
      between 201Tl defects with and without enhanced 201Tl uptake after reinjection.
      FDG activity, however, was present in all 12 regions (100%) with enhanced 201Tl
      uptake after reinjection as compared with only five of 35 (14%) that were
      unchanged after reinjection (p less than 0.01). CONCLUSIONS: Therefore, preserved
      wall thickness and systolic wall thickening in regions with moderate reduction in
      blood flow and FDG activity, and in irreversible 201Tl defects that are only mild
      to-moderate, provide additional evidence that such regions represent viable
      myocardium. Moreover, the finding of metabolic activity and 201Tl uptake in
      regions with reduced blood flow and absent wall thickening provides clinical
      evidence of hibernating myocardium in humans.

PMID- 1394921
TI  - Transcatheter ablation of ectopic atrial tachycardia in young patients using
      radiofrequency current.
AB  - BACKGROUND: Ectopic atrial tachycardia (EAT) is a reversible cause of
      cardiomyopathy but may be quite difficult to control with conventional therapy.
      Transcatheter ablation with radiofrequency current was tested as an alternative
      to medical or surgical treatment of this condition. METHODS AND RESULTS: Twelve
      young patients (aged 10 months to 19 years) with drug-resistant EAT were treated
      with direct transcatheter ablation of the ectopic focus using radiofrequency (RF)
      energy. All had depressed left ventricular contractility by echocardiographic
      criteria, involving shortening fractions of 10-26% (median, 20%; normal, 28-35%).
      The EAT was mapped to the left atrium in seven cases and to the right atrium in
      five. Local atrial activation at the ectopic site preceded the onset of the
      surface P wave by 20-60 msec (median, 42 msec). Tachycardia terminated 0.5-13.0
      seconds (median, 2.0 seconds) into a successful RF application. The ablation
      effectively eliminated EAT in 11 of 12 patients (92%), all of whom were
      discharged in sinus rhythm without medications after a median hospital stay of 48
      hours. Ablation was unsuccessful in one patient with diffuse dysplasia of the
      anterior right atrium, who eventually did well after surgical resection of
      abnormal atrial tissue. Transient depression of sinus node function was noted in
      one patient who had successful ablation of an EAT focus in close proximity to the
      sinus node, although normal sinus node function returned within 72 hours. No
      other complications were encountered. During follow-up (3-21 months; median, 13
      months), one patient had recurrence of a slower and less-sustained EAT that was
      successfully eliminated at a second ablation session. All others remained in
      sinus rhythm, and all 12 subjects recovered normal ventricular function.
      CONCLUSIONS: RF ablation appears to be a safe and effective therapeutic option
      for drug-resistant ectopic atrial tachycardia and may be the preferred first-line
      therapy for those patients with depressed ventricular function.

PMID- 1394922
TI  - Effect of Ebstein's anomaly on short- and long-term outcome of surgically treated
      patients with Wolff-Parkinson-White syndrome.
AB  - BACKGROUND: Ebstein's anomaly is the most commonly occurring congenital
      abnormality associated with the Wolff-Parkinson-White (WPW) syndrome. However,
      the effects of Ebstein's anomaly on the risks and benefits of surgical ablation
      of accessory pathways in patients with WPW syndrome are unknown. METHODS AND
      RESULTS: This study compared the long-term outcome of 38 WPW patients with
      Ebstein's anomaly undergoing accessory pathway ablation to a reference population
      of 384 similarly treated patients without the anomaly. Ebstein's anomaly was mild
      in 21 patients (55%) and moderate-to-severe in 17 patients (45%). Sixteen
      patients (42%) required tricuspid valve surgery, and 23 (61%) had an atrial
      septal defect or patent foramen ovale repaired. Baseline clinical characteristics
      and preoperative clinical arrhythmias were similar in both groups. Ten-year
      survival was 92.4% and 91.2% for patients with and without Ebstein's anomaly,
      respectively (p = NS). During a mean follow-up of 6.2 +/- 3.8 and 5.3 +/- 3.6
      years, 82% of patients with and 90% without Ebstein's anomaly had either
      clinically insignificant or no arrhythmias, and 18% versus 10% reported symptoms
      suggesting arrhythmias lasting longer than 1 minute, respectively. Atrial
      fibrillation was reduced postoperatively to 9% (p less than 0.001) in patients
      with and to 4% (p less than 0.001) in those without the anomaly. Fewer
      hospitalizations were reported postoperatively by 90% versus 96% of patients with
      and without Ebstein's anomaly; 9.4% versus 6.0% of patients were disabled at
      follow-up, respectively (p = NS). CONCLUSIONS: Patients with Ebstein's anomaly
      are improved significantly after accessory pathway ablation. The presence of this
      anomaly should not preclude accessory pathway ablation in these patients.

PMID- 1394923
TI  - Loss of the coronary microvascular response to acetylcholine in cardiac
      transplant patients.
AB  - BACKGROUND: The coronary arteries of transplanted hearts frequently develop
      accelerated diffuse arteriosclerosis. The effects of this disease on resistance
      vessel function are unknown. METHODS AND RESULTS: To investigate the integrity of
      endothelium-dependent small-vessel vasodilation in transplanted hearts, coronary
      blood flow (CBF) responses to the endothelium-dependent dilator acetylcholine
      (10(-8) to 10(-6) M) and the essentially endothelium-independent dilator
      adenosine (10(-6) to 10(-4) M) were assessed in 40 studies of 29 transplant
      patients 1-3 years after transplantation and in seven nontransplanted controls.
      CBF was measured at constant arterial pressure with a Doppler catheter in the
      left anterior descending coronary artery. Controls, year 1 transplant patients,
      and year 2 transplant patients had similar increases in CBF in response to
      acetylcholine (232 +/- 40%, 200 +/- 41%, and 201 +/- 54%, respectively; p = NS),
      whereas year 3 transplant patients had increased CBF of only 100 +/- 39% (p less
      than 0.05 versus controls). An index of the proportion of CBF reserve
      attributable to endothelium-dependent dilation was obtained by normalizing each
      patient's peak acetylcholine flow response by the peak adenosine flow response.
      In patients receiving both acetylcholine and adenosine, endothelium-dependent
      flow responses declined over time [57 +/- 9% in controls, 56 +/- 10% for year 1,
      47 +/- 12% for year 2, and 29 +/- 9% for year 3 (p less than 0.05 versus
      controls)]. An increased mean cyclosporine level (range, 99-261 ng/ml) (r = 0.67,
      p = 0.004) and increased transplant recipient age (range, 20-63 years) (r = 0.51,
      p = 0.004) predicted a preserved endothelium-dependent microvascular response.
      CONCLUSIONS: Thus, microvascular endothelium-dependent dilation deteriorates over
      time in the transplanted heart, which may reflect underlying graft
      arteriosclerosis and contribute to ischemic damage of the myocardium.

PMID- 1394924
TI  - Long-term predictors of subsequent cardiovascular events with coronary artery
      disease and 'desirable' levels of plasma total cholesterol.
AB  - BACKGROUND: Patients with coronary artery disease (CAD) are at considerable risk
      for subsequent cardiovascular events. Although hyperlipidemia accentuates the
      risk, predictors of subsequent events with CAD and desirable total cholesterol
      (TC) (less than 5.2 mmol/l) have not been assessed. METHODS AND RESULTS: A
      survival analysis was performed in a subset of 740 consecutive patients who
      underwent diagnostic coronary arteriography between 1977 and 1978. Eight-three
      men and 24 women with angiographically documented CAD and desirable TC were
      followed for subsequent cardiovascular events, including myocardial infarction
      and cardiovascular death. Over a 13-year period, 75% of CAD subjects with reduced
      high density lipoprotein cholesterol (HDL-C) (less than 0.9 mmol/l) developed a
      subsequent cardiovascular event compared with 45% of those with HDL-C greater
      than or equal to 0.9 mmol/l (p = 0.002). A Kaplan-Meier analysis revealed
      significantly greater survival from cardiovascular end points in patients with
      baseline levels of HDL-C greater than or equal to 0.9 mmol/l (p = 0.005). After
      11 variables were tested, an age-adjusted Cox proportional-hazards model
      identified two pairs of independent predictors of subsequent cardiovascular
      events: they were a left ventricular ejection fraction (LVEF) less than 35%
      (relative risk [RR], 6.5; 95% confidence interval [CI], 2.8, 15.3; p less than
      0.001) and reduced HDL-C (RR, 2.0; 95% CI, 1.2, 3.3; p = 0.01) in the first model
      and LVEF less than 35% (RR, 6.5; 95% CI, 2.7, 15.6; p less than 0.001) and TC:HDL
      ratio greater than or equal to 5.5 (RR, 1.9; 95% CI, 1.1, 3.1; p = 0.02) in the
      second model. CONCLUSIONS: Low HDL-C (or high TC:HDL-C) is strongly predictive of
      subsequent cardiovascular events in subjects with CAD, despite desirable TC. As
      such, identification of this potentially modifiable risk factor should be
      actively pursued in this high-risk subgroup.

PMID- 1394926
TI  - Platelet hyperaggregability across the coronary bed in response to rapid atrial
      pacing in patients with stable coronary artery disease.
AB  - BACKGROUND: Platelet aggregation is believed to contribute to the precipitation
      of acute ischemic syndromes. Because physical activity has been proposed as one
      possible trigger in converting a patient with chronic coronary artery disease to
      one with an acute ischemic syndrome, we examined the hypothesis that platelets
      become activated when coronary blood flow velocities (and thereby shear stress)
      increase across an atherosclerotic bed. METHODS AND RESULTS: During
      catheterization, 82 patients (36 with left coronary artery disease, 12 with only
      right coronary artery disease, and 34 with normal coronary arteries) had
      measurement of whole blood platelet aggregation performed on blood samples
      obtained simultaneously from the coronary sinus and aorta at rest, 2 minutes
      after onset of rapid atrial pacing, and 10 minutes after pacing was terminated.
      There was no arteriovenous difference in platelet aggregation under resting
      conditions in patients with versus those without coronary artery disease. Atrial
      pacing in patients with left coronary artery disease (greater than or equal to
      50% stenosis in a major epicardial vessel) caused an increase in platelet
      aggregation in the coronary sinus blood (+64 +/- 9%, p less than 0.01) but not in
      arterial blood (2 +/- 8% decrease, p = NS). This increase was transient and
      returned nearly to baseline 10 minutes after termination of pacing. Patients with
      nonsignificant left coronary artery disease, those with normal coronary arteries,
      and patients with significant disease only in the right coronary artery (venous
      drainage not into the coronary sinus) did not show any changes in either the
      coronary sinus or arterial blood with atrial pacing. CONCLUSIONS: There is no
      evidence of platelet activation across a normal or an atherosclerotic coronary
      bed at rest. When coronary blood flow increases in the presence of significant
      (greater than or equal to 50%) narrowing of epicardial coronary arteries,
      however, platelets are activated and aggregate more easily. This mechanism may
      play a role in the precipitation of acute ischemic syndromes in patients with
      coronary artery disease.

PMID- 1394925
TI  - Endothelial dysfunction early after heart transplantation. Assessment with
      intravascular ultrasound and Doppler.
AB  - BACKGROUND: Allograft vasculopathy after heart transplantation is thought to
      represent a response to endothelial injury in the graft vessels. To assess
      endothelial function before the onset of anatomic disease, coronary vasomotor
      responses to adenosine, acetylcholine, and nitroglycerin were evaluated in
      transplant recipients by intravascular ultrasound imaging and Doppler flow
      studies. METHODS AND RESULTS: Nine patients were studied 1 year after heart
      transplantation. Acetylcholine provoked significant vasoconstriction to 82% of
      maximal coronary diameter but was associated with an increase in mean coronary
      blood flow from 63.1 to 204 ml/min. Coronary blood flow increased fivefold in
      response to adenosine, a normal response. CONCLUSIONS: The vasomotor response to
      acetylcholine at 1 year after heart transplantation is consistent with
      endothelial dysfunction in the epicardial conduit vessels. Microvascular function
      as judged by coronary flow reserve appears to be normal.

PMID- 1394927
TI  - Clinical characteristics and outcome of patients with high defibrillation
      thresholds. A multicenter study.
AB  - BACKGROUND: Successful defibrillation by an implantable cardioverter
      defibrillator (ICD) depends on its ability to deliver shocks that exceed the
      defibrillation threshold. This study was designed to identify clinical
      characteristics that may predict the finding of an elevated defibrillation
      threshold and to describe the outcome of patients with high defibrillation
      thresholds. METHODS AND RESULTS: The records of 1,946 patients from 12 centers
      were screened to identify 90 patients (4.6%) with a defibrillation threshold
      greater than or equal to 25 J. Excluding three patients who received ICDs that
      delivered greater than 30 J, there were 81 men and six women with a mean age of
      59.5 +/- 10.1 years, a mean left ventricular ejection fraction of 0.32 +/- 0.14,
      and a 76% prevalence of coronary artery disease. Sixty-one patients (70%) were
      receiving antiarrhythmic drugs, and 45 (52%) were receiving amiodarone. Seventy
      one patients (82%) received an ICD. Death occurred in 27 patients--19 of the 71
      (27%) with an ICD (eight arrhythmic), and eight of the 16 (50%) without an ICD
      (four arrhythmic). Actuarial survival for all patients at 5 years was 67%.
      Actuarial survival rates at 2 years for patients with and without an ICD were 81%
      and 36%, respectively (p = 0.0024). Actuarial survival at 5 years for the ICD
      patients was 73%; no patient without an ICD has lived longer than 32 months.
      Actuarial survival free of arrhythmic death in the ICD patients at 5 years was
      84%. Although the only variable to predict survival was ICD implantation (p =
      0.003), it is entirely possible that in this retrospective analysis, clinical
      selection decisions to implant or to not implant an ICD differentiated patients
      destined to have better or worse outcomes, respectively. CONCLUSIONS:
      Antiarrhythmic drug use may be causally related to the finding of an elevated
      defibrillation threshold. When patients with high defibrillation thresholds
      receive an ICD, arrhythmic death remains an important risk (42% of deaths in
      these patients were arrhythmia related, with 16% actuarial incidence at 5 years).
      Vigorous testing to optimize patch location can potentially benefit patients by
      enhancing the margin of safety for effective defibrillation.

PMID- 1394928
TI  - Failure of an implantable cardioverter-defibrillator to redetect ventricular
      fibrillation in patients with a nonthoracotomy lead system.
AB  - BACKGROUND: Shock delivery of an implantable defibrillator may cause a change in
      the amplitude of endocardial electrograms and impair the detection of ventricular
      fibrillation. Thus, the effects of shock discharges on the amplitude of
      endocardial electrograms were evaluated in five patients undergoing implantation
      of a cardioverter-defibrillator in combination with a new nonthoracotomy lead
      system. METHODS AND RESULTS: At implant, bipolar endocardial electrograms were
      recorded before each shock application, during ventricular fibrillation, during
      redetection of ventricular fibrillation in case the applied shock was
      ineffective, and at intervals of 5, 10, 20, 30, 60, and 120 seconds after each
      shock delivery. The amplitude of the endocardial electrograms decreased from 10.5
      +/- 3.8 mV during sinus rhythm to 6.3 +/- 1.9 mV during initial ventricular
      fibrillation and declined to 2.2 +/- 1.3 mV during redetection of ventricular
      fibrillation. After successful termination, the following bipolar electrograms
      could be obtained at the predetermined intervals: 1.9 +/- 1.2 mV, 3.1 +/- 1.8 mV,
      4.5 +/- 1.9 mV, 6.5 +/- 2.9 mV, 9.5 +/- 3.3 mV, and 10.4 +/- 3.8 mV. At
      predischarge testing, failure of redetection of ventricular fibrillation could be
      documented in two patients, requiring rescue external defibrillation in both
      cases to restore sinus rhythm. CONCLUSIONS: These findings demonstrate that the
      implantable cardioverter-defibrillator did not ensure reliable redetection of
      ventricular fibrillation in patients using the implanted nonthoracotomy lead
      system. Thus, the potential risk of sudden cardiac death may persist in these
      patients despite defibrillator therapy.

PMID- 1394929
TI  - Radiofrequency catheter ablation for the treatment of human type 1 atrial
      flutter. Identification of a critical zone in the reentrant circuit by
      endocardial mapping techniques.
AB  - BACKGROUND: Recent studies of human type 1 atrial flutter demonstrated reentry in
      the right atrium and an area of slow conduction in the low posteroseptal right
      atrium. Direct-current catheter ablation of this area has been only moderately
      successful in preventing recurrence. Therefore, we performed endocardial
      activation mapping and entrainment pace mapping during atrial flutter to
      determine the critical site for radiofrequency ablation of this arrhythmia.
      METHODS AND RESULTS: Twelve consecutive patients (seven men and five women; age,
      21-73 years) with type 1 atrial flutter (mean cycle length, 253 +/- 39 msec)
      underwent right atrial endocardial activation and entrainment pace mapping using
      standard transvenous catheter techniques to localize the atrial flutter reentrant
      circuit, the area of slow conduction, and the exit site from the area of slow
      conduction. Upon identifying appropriate sites, radiofrequency energy (16-29 W)
      was applied via a 4-mm tipped catheter. Activation mapping of atrial flutter
      revealed a counterclockwise reentrant wave front originating just inferior or
      posterior to the coronary sinus ostium, proceeding superiorly in the atrial
      septum to the right atrial free wall, then inferiorly toward the tricuspid
      annulus and finally medially between the inferior vena cava and the tricuspid
      annulus, where low-amplitude fragmented electrical activity was noted.
      Entrainment pace mapping from this area produced an exact P wave match to atrial
      flutter on 12-lead ECG with a long (greater than 40 msec) stimulus-to-P interval
      indicating slow conduction, whereas pacing just inferior or posterior to the
      coronary sinus ostium produced an exact P wave match with a short stimulus-to-P
      interval (less than 40 msec), presumably identifying the exit site from the area
      of slow conduction. Radiofrequency energy (one to 14 applications) was effective
      in terminating and preventing reinduction of atrial flutter in 10 patients. In
      two patients, atrial flutter was not terminated during radiofrequency energy
      application but during subsequent pacing attempts. Sites where ablation was
      successful, located just inferior or posterior to the coronary sinus ostium, were
      characterized by discrete electrograms with activation times of -20 to -50 msec
      before P wave onset and exact entrainment pace maps with a stimulus-to-P interval
      of 20 to 40 msec, consistent with the exit site from the area of slow conduction.
      Follow-up (mean, 16 +/- 9 weeks; range, 2-31 weeks) revealed recurrence of the
      original atrial flutter in two patients, one of whom underwent repeat ablation
      without further recurrence, self-limited infrequent recurrence of a new atrial
      flutter or atrial fibrillation in three suppressed by beta-blocker or digoxin,
      and no recurrence in seven. CONCLUSIONS: 1) Radiofrequency energy applied to a
      critical area in the atrial flutter reentrant circuit, inferior or posterior to
      the coronary sinus ostium, will terminate and prevent arrhythmia reinduction. 2)
      Long-term follow-up in a larger series of patients will be required to confirm
      efficacy of this technique, although short-term results look promising.

PMID- 1394930
TI  - Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary
      hypertension.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a disorder
      characterized by pulmonary arterial hypertension as a consequence of organized
      thrombotic material in the central pulmonary arteries. Incomplete resolution of
      acute pulmonary emboli is believed to be pathogenically important; however, the
      mechanism for poor thrombus dissolution remains to be explained. We undertook
      this study to assess the major determinants of plasma fibrinolysis in patients
      with CTEPH (n = 32). METHODS AND RESULTS: Immunological and functional levels of
      tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator
      inhibitor (PAI-1) were quantified in platelet-poor plasma (PPP) from patients
      with CTEPH as well as age-matched controls. Although basal PPP t-PA antigen
      levels (CTEPH mean, 29.5 ng/ml; control mean, 2.7 ng/ml) and PAI-1 antigen levels
      (CTEPH mean, 55.8 ng/ml; control mean, 21.0 ng/ml) were higher in the CTEPH
      group, no between-group differences were detected in the enzymatic activities of
      these two molecules. The CTEPH group demonstrated a greater rise in t-PA antigen
      (CTEPH mean rise, 53.0 ng/ml; control mean rise, 5.6 ng/ml) and PA activity
      (CTEPH mean rise, 10.5 IU/ml; control mean rise, 1.2 IU/ml) than controls in
      response to an experimentally induced venous occlusion. Immunoprecipitation and
      fibrin autography of PPP from two patients with markedly elevated basal t-PA
      antigen levels demonstrate that the t-PA antigen was present in PPP primarily in
      complex with PAI-1. CONCLUSIONS: Although abnormalities of the fibrinolytic
      system were detected, neither a high resting plasma PAI-1 activity nor a blunted
      response of t-PA to venous occlusion can be invoked as an etiology for CTEPH:

PMID- 1394932
TI  - Effect of ultrasound on tissue-type plasminogen activator-induced thrombolysis.
AB  - BACKGROUND: The efficacy of fibrinolytic therapy is limited by the small surface
      area of the clot that is available for the binding of the thrombolytic agent,
      such as tissue-type plasminogen activator (t-PA). We hypothesized that exposure
      of the clot to ultrasound during thrombolytic treatment could enhance lysis
      through perturbation of the thrombus, which would expose additional fibrin
      binding sites for t-PA. METHODS AND RESULTS: Whole human blood clots containing
      radiolabeled fibrinogen were incubated in vitro for 200 minutes with Tris-albumin
      buffer containing t-PA at concentrations ranging from 3 to 3,000 IU/ml. In paired
      experiments, one of the clots also was exposed to intermittent ultrasound (1 MHz,
      1.75 W/cm2) throughout the experiment. The ultrasound was delivered as a 2-second
      exposure followed by a 2-second rest interval. The overall difference in mean
      clot lysis between thrombi receiving ultrasound and those receiving no ultrasound
      was significant (p less than 0.001) at all concentrations of t-PA. For clots
      incubated with t-PA at a concentration of 300 IU/ml, ultrasound increased the
      percent lysis at 200 minutes from 42 +/- 5% (mean +/- SEM) to 64 +/- 10%. In six
      paired experiments in a rabbit jugular vein thrombosis model, rabbits received 1
      mg t-PA alone or t-PA and intermittent ultrasound (1 MHz, 1.75 W/cm2) for 200
      minutes. For rabbits receiving ultrasound and t-PA, lysis was 55 +/- 11% at 100
      minutes compared with 30 +/- 12% for rabbits receiving only t-PA. Lysis was 6 +/-
      10% for rabbits (n = 4) receiving ultrasound alone. No evidence for tissue damage
      was noted in rabbits exposed to intermittent ultrasound. CONCLUSIONS: Exposure of
      whole blood clots in vitro to intermittent ultrasound combined with t-PA caused a
      significant enhancement of thrombolysis compared with t-PA alone. Intermittent
      ultrasound also showed a trend toward enhancement of t-PA-induced clot lysis in
      an animal thrombosis model. These data suggest that noninvasive intermittent
      ultrasound may be a useful adjunct to thrombolytic therapy.

PMID- 1394931
TI  - Dose-dependent smooth muscle cell proliferation induced by thermal injury with
      pulsed infrared lasers.
AB  - BACKGROUND: Recently, laser-heated and radio frequency-heated balloon angioplasty
      techniques have been proposed as a means to treat or minimize dissection and
      elastic recoil but have been associated with a high rate of clinical restenosis.
      Similarly, pulsed laser angioplasty techniques proposed to minimize thermal
      injury while ablating obstructing atheroma have failed to reduce clinical
      restenosis. Because "hot balloon" and pulsed laser angioplasty create both
      mechanical and thermal injury, it has been difficult to discern the cause of the
      smooth muscle cell (SMC) proliferation resulting in restenosis and whether such
      magnitude of proliferation is predictable and dose related. This study was
      undertaken to explore these issues. METHODS AND RESULTS: Localized thermal
      lesions accompanying efficient ablation were created with a pulsed Tm:YAG laser
      in nine rabbit aortas, which consistently led to a focal proliferation of SMC
      that filled the ablated region by 4 weeks. Transcutaneous Ho:YAG pulsed laser
      irradiation at multiple independent sites of 24 central rabbit ear arteries
      without ablation led to brief approximately 30 degrees C thermal transients and
      thermal damage to the artery wall resulting in significant neointimal
      proliferation by 3 weeks and a mean cross-sectional narrowing of 59 +/- 17% at a
      dose of 390 mJ/mm2. Acute and chronic responses to varying total energy
      deposition were studied by histology after the rabbits were killed at 2 hours to
      4 weeks. Arterial segments midway between laser injuries were unaffected and
      served as internal controls. Neointimal proliferation at 3 weeks after laser
      injury exhibited a clear dose dependence. Mean cross-sectional narrowing
      increased from 34 +/- 10% to 85 +/- 15% as laser fluence increased from 240
      mJ/cm2 to 640 mJ/cm2 (r = 0.84). Similarly, cross-sectional narrowing caused by
      SMC neointimal proliferation increased from 20 +/- 10% to 77 +/- 17% for a fixed
      surface irradiation as the depth of the most superficial arterial media decreased
      from 600 microns to 330 microns (r = 0.94). CONCLUSIONS: Thermal injury to the
      arterial wall is a potent stimulus for SMC proliferation and may necessitate
      reduction in laser or thermal energy used for angioplasty. Moreover, a dose
      response relation exists between the degree of thermal injury and SMC
      proliferative response. Hence, this technique could be used as a practical model
      of restenosis suitable for screening therapies for inhibition of SMC
      proliferation.

PMID- 1394933
TI  - Myocardial function and transmural blood flow during coronary venous
      retroperfusion in pigs.
AB  - BACKGROUND: The degree of recovery of regional myocardial contraction during
      coronary venous retroperfusion has not been well established, particularly in the
      absence of coronary collateral channels. Therefore, the maximal functional
      benefit attainable with coronary venous retroperfusion was assessed in pigs by
      means of using selective pump retroperfusion of the left anterior descending
      vein, with venting of the left anterior descending artery to zero pressure.
      METHODS AND RESULTS: In eight anesthetized open-chest pigs during selective left
      anterior descending venous retroperfusion over a range of retroperfusion flows,
      regional myocardial function (percent systolic wall thickening by sonomicrometry)
      increased progressively to an average of 62% of control values at a
      retroperfusion flow rate 200% of control arterial flow. Progressive thickening of
      the end-diastolic dimension of the anterior wall was observed with increasing
      retroperfusion flow (from 8.7 +/- 0.9 to 10.7 +/- 2.3 mm, p less than 0.001).
      Perfusion pressures within the left anterior descending vein increased linearly
      with increased retroperfusion flow rates (up to 132 +/- 57 mm Hg with
      retroperfusion flow 200% of control). A gradual increase of retrograde left
      anterior descending arterial outflow was observed with increasing retroperfusion
      flows; however, the absolute amount (maximum, 8.3 +/- 4.1 ml/min) was much too
      low to explain the extent of functional recovery. Transmural myocardial capillary
      blood flows in the anterior wall with retroperfusion flows of 100% and 200% of
      control arterial flow were 0.22 and 0.42 ml/min/g with corresponding
      subendocardial blood flows of 0.14 and 0.29 ml/min/g; ratios of endocardium to
      epicardium were 0.51 and 0.61, respectively. Thus, capillary blood flows during
      selective retroperfusion were relatively low despite considerable restoration of
      regional systolic wall thickening, and a significant difference was noted in the
      slopes of the relations between regional systolic wall thickening and myocardial
      blood flow during retroperfusion and anterograde arterial perfusion (p less than
      0.05). With retrograde injection of silicone elastomer at different
      retroperfusion pressures (50, 75, and 100 mm Hg) in three pigs, capillaries were
      well visualized, and profuse intramyocardial venous anastomotic connections were
      seen at the highest retroperfusion pressure (100 mm Hg), whereas there was
      filling of small venules but little capillary filling at the lowest
      retroperfusion pressure (50 mm Hg). CONCLUSIONS: Considerable recovery of
      regional myocardial function with low regional capillary blood flows were
      observed during acute venous retroperfusion with high retroperfusion flows with
      arterial blood. These findings together with low levels of retrograde arterial
      outflow and visualization of retrograde capillary filling with a rich venous
      network provide evidence for possible oxygen delivery via the intramyocardial
      venous plexus.

PMID- 1394934
TI  - Changes in the radius of curvature of the ventricular septum at end diastole
      during pulmonary arterial and aortic constrictions in the dog.
AB  - BACKGROUND: At end diastole, the position and shape of the ventricular septum
      depend on the transseptal pressure gradient. It is not clear, however, how the
      septal radius of curvature changes in response to the gradual change in
      transseptal pressure gradient during progressive pulmonary arterial constriction
      (PAC) and aortic constriction (AC). METHODS AND RESULTS: In 11 anesthetized open
      chest dogs, the septal radius of curvature was measured from the short-axis two
      dimensional echocardiogram, and the transseptal pressure gradient (left
      ventricular [LV] pressure minus right ventricular [RV] pressure) was calculated
      from ventricular pressures measured with micromanometers. Seven dogs were studied
      with both PAC and AC (group 1) and four dogs only with PAC, which was initiated
      before and after volume loading (group 2). The transseptal pressure gradient
      decreased during PAC. As the transseptal pressure gradient decreased, the septum
      shifted continuously leftward with decreases in the LV septum-free wall diameter
      and in LV cross-sectional area. The septal radius of curvature (Rs) increased
      until the septum became flat. The flat septum (i.e., Rs = infinity) occurred at a
      relatively constant value of transseptal pressure gradient (-4.6 +/- 1.4 mm Hg)
      independently of the absolute values of LV pressures when between 2 and 9 mm Hg,
      although necessarily a greater RV pressure was needed to make the septum flat
      when LV pressure was higher. After inversion, the septum again became curved,
      with a decrease in the absolute value of septal radius of curvature as the
      transseptal pressure gradient became increasingly negative. The septum was still
      concave to the LV cavity at zero transseptal pressure gradient, and its curvature
      decreased (i.e., its radius of curvature increased) with increases in ventricular
      pressures. During AC, the septal radius of curvature also increased, but with an
      increase in transseptal pressure gradient accompanied by increases in LV septum
      free wall diameter and in LV area. In group 2 animals, at zero transseptal
      pressure gradient, the normalized septal radius of curvature was greater (p less
      than 0.005) at high LV pressure than at low LV pressure. The transseptal pressure
      gradient required to make the septum flat was not significantly different between
      low and high LV pressure, which confirmed the results of group 1. CONCLUSIONS:
      The results of the present study show that the shape and position of the
      ventricular septum are determined by the transseptal pressure gradient but that
      the shape of the septum is also affected by the ventricular pressures. The septum
      was not flat but rather still concave to the LV cavity at zero transseptal
      pressure gradient. Approximately 5 mm Hg of negative transseptal pressure
      gradient was required to displace the septum farther leftward and make it flat.
      The septal radius of curvature increased during both PAC (which decreased
      transseptal pressure gradient) and AC (which increased transseptal pressure
      gradient), indicating that the mechanisms involved in changing septal radius of
      curvature are different during PAC and AC.

PMID- 1394935
TI  - Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with
      dobutamine.
AB  - BACKGROUND: We hypothesized that the effect of pimobendan (UD-CG 115 BS) to
      increase calcium sensitivity of contractile protein might result in less
      myocardial oxygen consumption (VO2) in comparison with dobutamine when they
      enhance ventricular contractility to the same extent. To examine this hypothesis,
      we compared the effects of pimobendan and dobutamine on left ventricular
      contractility and energetics using the frameworks of Emax (contractility index)
      and the relation between VO2 and PVA (systolic pressure-volume area, a measure of
      left ventricular total mechanical energy). METHODS AND RESULTS: We measured VO2,
      Emax, PVA, and force-time integral (FTI) in excised, cross-circulated, nonfailing
      dog hearts. The slope of the VO2-PVA relation reciprocally indicates the
      efficiency from PVA-dependent VO2 to the total mechanical energy (contractile
      efficiency). The VO2 intercept of the VO2-PVA relation, i.e., PVA-independent
      VO2, reflects energy utilization for excitation-contraction coupling. The ratio
      of FTI to PVA-dependent VO2 can be called contractile economy. Both drugs
      comparably enhanced Emax. Although the contractile economy was greater by 14 +/-
      19% (p less than 0.05) for pimobendan than for dobutamine, the contractile
      efficiency was similar between the two drugs. Oxygen cost of contractility,
      defined as the slope of the relation between the PVA-independent VO2 and Emax,
      was the same between the two drugs. Other mechanoenergetic effects of both drugs
      were similar except for a greater coronary vasodilating effect of pimobendan.
      CONCLUSIONS: Pimobendan has almost the same mechanoenergetic effects as
      dobutamine but slightly greater contractile economy and coronary vasodilation.
      The calcium-sensitizing effect of pimobendan did not save the oxygen cost of
      contractility.

PMID- 1394936
TI  - Endogenous nitric oxide protects against platelet aggregation and cyclic flow
      variations in stenosed and endothelium-injured arteries.
AB  - BACKGROUND: This study was designed to test the hypothesis that endogenously
      produced nitric oxide protects against platelet aggregation and cyclic flow
      variations in stenosed and endothelium-injured arteries of mongrel dogs. METHODS
      AND RESULTS: NG-Monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide
      formation, was administered at 5 mg/kg to 15 dogs after the left anterior
      descending coronary artery was mechanically injured and narrowed by external
      constrictors and to nine dogs before endothelial injury of the femoral artery and
      after injury and moderate arterial constriction. Treatment with L-NMMA resulted
      in cyclic flow variations (as detected by external Doppler flow probes) in the
      left anterior descending artery of seven of 15 dogs and in the femoral artery of
      four of nine dogs after endothelial injury. L-Arginine, the precursor for nitric
      oxide synthesis, was administered at 60 mg/kg and abolished cyclic flow
      variations in each of the 11 dogs. D-Arginine did not change the L-NMMA-induced
      cyclic flow variations. Saline infusion did not induce or change cyclic flow
      variations in any of the animals. Acetylcholine (1, 10, and 100 micrograms/min; n
      = 9) was administered in the femoral artery of nine additional dogs before and
      after endothelial injury in moderately stenosed femoral arteries. Acetylcholine
      did not induce cyclic flow variations in any animal; however, it did increase the
      severity of cyclic flow variations that developed in severely stenosed arteries.
      The diameter of the femoral artery was measured by intravascular ultrasound
      imaging. L-NMMA caused vasoconstriction of normal arteries, but no change was
      detected in endothelium-injured arteries. In contrast, L-arginine caused
      vasodilation of normal arteries, but, again, no change was noted in endothelium
      injured arteries. Acetylcholine dilated normal femoral arteries but constricted
      arteries with endothelial injury. In both in vitro and ex vivo platelet studies,
      L-NMMA enhanced platelet aggregation, whereas L-arginine significantly reduced
      platelet aggregation. D-Arginine and acetylcholine showed no effect on platelet
      aggregation. CONCLUSIONS: Promotion of nitric oxide production decreases platelet
      aggregation and may eliminate cyclic flow variations, whereas a reduction in
      nitric oxide formation enhances platelet aggregation and may induce cyclic flow
      variations. Acetylcholine causes vasoconstriction at the femoral arterial site of
      endothelial injury and may increase the severity of cyclic flow variations.

PMID- 1394937
TI  - Role of myocardial ATP-sensitive potassium channels in mediating preconditioning
      in the dog heart and their possible interaction with adenosine A1-receptors.
AB  - BACKGROUND: A brief period of myocardial ischemia can result in an increased
      resistance to subsequent, more severe episodes of ischemia. Recent studies have
      indicated that activation of adenosine A1-receptors may mediate this
      preconditioning effect. It is also known that A1-activation can lead to ATP
      sensitive potassium channel (KATP) opening via a G(i) protein-mediated effect.
      Thus, we determined whether the KATP blocker glyburide could abolish
      preconditioning or the protective effects of A1-receptor activation. METHODS AND
      RESULTS: Anesthetized dogs were subjected to 5 minutes of left circumflex
      coronary artery (LCx) occlusion (or sham) followed by 10 minutes of reperfusion.
      The hearts were then subjected to 60 minutes of LCx occlusion and 5 hours of
      reperfusion. Glyburide (5 micrograms/kg/min) or vehicle was given directly into
      the LCx 20 minutes before preconditioning or sham preconditioning.
      Preconditioning resulted in a significantly reduced infarct size compared with
      nonpreconditioned animals. Glyburide abolished the protective effect of
      preconditioning. To establish a link between KATP and A1-receptor activation, the
      effect of the A1-agonist R-PIA with or without glyburide on infarct size was
      determined. R-PIA (0.4 microgram/kg/min, directly into the LCx) significantly
      reduced infarct size, and this protective effect was abolished by glyburide. None
      of the treatments described above had a significant effect on peripheral
      hemodynamic status or myocardial blood flow. CONCLUSIONS: Preconditioning may be
      mediated by KATP activation, and this may be linked to A1-receptor stimulation.

PMID- 1394938
TI  - Left atrial contribution to ventricular filling during the course of evolving
      heart failure.
AB  - BACKGROUND: Abnormal left ventricular (LV) filling has been observed in patients
      with heart failure and is characterized by marked heterogeneity of mitral inflow
      velocity. In the present study, the contribution of the left atrium to LV filling
      was examined in eight dogs during the course of evolving heart failure. METHODS
      AND RESULTS: Heart failure was produced by multiple sequential intracoronary
      embolizations with microspheres. Pulsed Doppler echocardiography was used to
      measure mitral inflow velocity at baseline, before embolization, and at 3, 8, 15,
      23, and 33 weeks after initiation of microembolization. The early rapid LV
      filling (Ei) and late left atrial filling (Ai) components were quantitated based
      on the time-velocity integral of the early and late mitral inflow velocity
      waveforms, respectively. Ei decreased progressively from 7.6 +/- 1.5 cm at
      baseline to 4.0 +/- 0.4 cm at 33 weeks (p less than 0.01). In contrast, Ai
      initially increased from 1.8 +/- 0.9 cm at baseline to 2.7 +/- 0.4 cm at 3 weeks
      (p less than 0.01) and subsequently decreased gradually to below baseline values
      reaching 0.8 +/- 0.4 cm at 33 weeks (p less than 0.01). These temporal changes of
      Ei and Ai were accompanied by a gradual reduction of LV ejection fraction (56 +/-
      5% versus 22 +/- 2%) (p less than 0.01) (baseline versus 33 weeks) and by a
      gradual increase of LV end-diastolic wall stress (24 +/- 7 versus 92 +/- 8 g/cm2)
      (p less than 0.01), left atrial dimension (2.4 +/- 0.2 cm to 3.3 +/- 0.3 cm) (p
      less than 0.01), and left atrial fractional shortening (22 +/- 3% versus 15 +/-
      2%) (p less than 0.01). CONCLUSIONS: The initial rise in left atrium contribution
      to LV filling may represent a compensatory response to the diminution of the
      rapid early component of LV filling. With further progression of LV dysfunction,
      the left atrium contribution to LV filling gradually decreased. This reduction
      may be mediated by increased workload imposed on the left atrial myocardium due
      to increased LV diastolic wall stress, which, over time, may have lead to
      intrinsic left atrium dysfunction.

PMID- 1394939
TI  - Ancel Keys Lecture. The three beauties. Bench, clinical, and population research.

PMID- 1394940
TI  - Oral anticoagulant therapy. Urgent need for standardization.

PMID- 1394941
TI  - Sex-associated differences in left ventricular function in aortic stenosis of the
      elderly.

PMID- 1394942
TI  - Successful transcatheter ablation of ectopic atrial tachycardia in young patients
      using radiofrequency current.

PMID- 1394943
TI  - Desirable serum total cholesterol with low HDL cholesterol levels. An undesirable
      situation in coronary heart disease.

PMID- 1394944
TI  - Efficacy of nisoldipine.

PMID- 1394945
TI  - Training standards for physicians performing peripheral angioplasty and other
      percutaneous peripheral vascular interventions. A statement for health
      professionals from the Special Writing Group of the Councils on Cardiovascular
      Radiology, Cardio-Thoracic and Vascular Surgery, and Clinical Cardiology, the
      American Heart Association.

PMID- 1394946
TI  - Abstracts from the 65th Scientific Sessions, American Heart Association. New
      Orleans, Louisiana, November 16-19, 1992.

PMID- 1394947
TI  - [Normalization of acupuncture anesthesia used in neurosurgery].
AB  - From March 1975 to February 1982 and from April 1987 to October 1990, the
      national cooperative neurosurgical acupuncture research group had already
      accumulated the clinic data of 5,244 cases totally, consisting of 2,107 cases in
      frontal fossa, 1951 cases in the temporo-parieto-occipital region and 1,186 in
      posterior fossa. By the same manipulative procedures and scaling criteria, the
      indications, choices of acupoints, stimulus parameters, adjuvants, preoperative
      measurements, and physiological and biochemical changes during operations were
      studied. Practically, the results was not only reliable, but repetitive highly.
      95% of the cases in frontal fossa belonged to grade I (success), 91.5% of the
      cases in temporo-parieto-occipital region was grade I and 89.38% of the cases in
      posterior fossa was grade I. We suggest that acupuncture anesthesia should be
      widely used as one of the usual methods of anesthesia. In this paper, the
      relative specificity of acupoints, the mechanism of adjuvants, personal
      differences and preoperative measurements were discussed. In the meantime, the
      advantages and the remaining problems of acupuncture anesthesia in craniocerebral
      operations were also mentioned.

PMID- 1394948
TI  - [Effect of prefrontal cortex on the neuronal activity of the nucleus raphe magnus
      in rats].
AB  - The unit discharge of neurons in nucleus raphe magnus (NRM) were recorded with
      glass microelectrodes in 33 waking and tubocurarine-immobilized rats. It is
      observed that effects of the noxious stimulation and prefrontal cortex (PFC)
      stimulation on spontaneous discharges of NRM neurons and effects of PFC
      stimulation on noxious-evoked discharges of NRM neurons by stimulating sural
      nerve. The results indicated that noxious stimulation and PFC stimulation could
      increase spontaneous discharge of most (68.18% and 60.82% respectively) NRM
      neurons. It was also noted that most (49/80) NRM neurons altered their
      spontaneous discharge in response to noxious stimulation and PFC stimulation in a
      similar manner. The remainder (31/80) opposite manners. PFC stimulation could
      alter the response of NRM neurons to noxious stimulation. PFC stimulation could
      enhance or reduce noxious-evoked discharge in NRM neurons which alter their
      spontaneous discharge in response to noxious stimulation and PFC stimulation in a
      similar manner. PFC stimulation could reduce noxious-evoked discharge in NRM
      neurons which alter their spontaneous discharge in opposite manners. The above
      results suggest that PFC and NRM have a functional relation. PFC could modulate
      nociceptive response and it might be partly responsible for influence on activity
      of neurons in NRM.

PMID- 1394949
TI  - [Comparison of effects of EA at "hegu" on nociceptive responses of NRM neurons to
      noxious stimulation of the face and tail].
AB  - The experiments were performed on the rats. Unit discharges in NRM and their
      nociceptive responses to dental pulp and tail noxious stimulations were recorded
      extracellularly with glass microelectrodes. We observed that EA at the "Hegu"
      acupoint could increase spontaneous discharges of NRM neurons and inhibit their
      nociceptive responses to noxious stimulation acting on dental pulp and tail. It
      is interestingly noted that the inhibitory effect of EA on noxious stimulation
      applying on the pulp is stronger than the tail.

PMID- 1394950
TI  - Influence of acupuncture on the discharge of PHA neurons in the rabbit.
AB  - This paper deals with whether the posterior hypothalamus area (PHA) can receive
      signals from electroacupuncture (EA) at "Neiguan", and whether a relative
      specificity does exist between acupoints or acupoint and non-acupoint. The neuron
      activity was recorded extracellularly for analyzing the influence of EA at
      different acupoints and non-acupoint on the discharge of PHA neurons.

PMID- 1394951
TI  - [Effects of head point needling on cardiac function and hemodynamics].
AB  - The present investigation was undertaken to observe the effects of head point
      cardiovascular point needling on the cardiac function and hemodynamics in 8
      anesthetized dogs, and to elucidate the underlying mechanisms and its clinical
      implications. Cardiovascular point needling might induce significant changes in
      cardiac function and hemodynamic parameters: arterial systolic pressure decreased
      by 22.4 +/- 8.88 from 104.6 +/- 20.55 mmHg, diastolic pressure by 16.7 +/- 8.04
      from 66.5 +/- 18.03 mmHg, mean arterial pressure by 18.6 +/- 8.16 from 79.2 +/-
      18.36 mmHg, left ventricular end-diastolic pressure by 0.3 +/- 0.47 from 3.6 +/-
      1.94 mmHg, Lv dp/dt max by 300.1 +/- 200.1 from 2000.1 +/- 700.8 mmHg/s, coronary
      resistance by 399 +/- 310 from 1959 +/- 1150 dyn.s.cm-5, femoral arterial
      resistance by 242 +/- 634 from 2438 +/- 1595 dyn.s.cm-5, total peripheral
      resistance by 1570.7 +/- 691.0 from 9000.2 +/- 2537.4 dyn.s.cm-5, and left
      ventricular work index by 2.7 +/- 1.9 from 11.4 +/- 5.17 kg.m/min/m2, whereas the
      coronary sinus blood flow increased by 0.7 +/- 1.6 from 33.6 +/- 14.7 ml/min.
      There were significant differences between the values of all parameters before
      and after cardiovascular point needling (p greater than 0.005). The results
      indicated that cardiovascular point needling was capable of lowering the cardiac
      preload and afterload with resultant fall in blood pressure and cardiac oxygen
      consumption, as well as relaxing the coronary vessels and consequent increase in
      coronary blood flow with enhanced oxygen supply. These beneficial effects induced
      by cardiovascular point needling provided the basis for the treatment of
      hypertension, coronary artery diseases and cardiac failure in clinic.

PMID- 1394952
TI  - [Effect of electroacupuncture on myocardial oxygen metabolism and pH of coronary
      sinus blood during experimental angina pectoris].
AB  - The experiments were performed on 30 healthy mongrel dogs, intubation was taken
      in the left anterior descending coronary (LAD), the blood in carotid was
      transported to LAD through a peristalic pump, the blood flow was reduced to 3-5
      ml/min, thus acute myocardial ischemia was produced. Basing on this condition,
      0.1-0.16 ml bradykinin (2 ug/ml) was given into LAD coronary before recording to
      produce angina pectoris. The effects of electroacupuncture (EA) at "Neiguan" area
      on myocardial oxygen metabolism, pH of coronary sinus blood and myocardial
      contractile force were observed (EA intensity 5 volts, frequency 1-20 Hz). The
      results are as follows: 1. EA could reduce obviously A-V difference of blood
      oxygen capacity (Ca-vO2) and the rate of myocardium extracting oxygen (O2E), thus
      reduced obviously oxygen consumption of ischemic myocardium. 2. EA could reduce V
      A difference of carbon dioxide partial pressure (Pv-aCO2), prevent the decrease
      of pH of coronary sinus blood (PHv), this indicated that EA could prevent
      accumulation of acidic metabolic products. 3. EA could increase myocardial
      developed tension (DT) of ischemic area, strengthen myocardial contractile force
      of ischemic area. Above results indicated that EA could reduce oxygen consumption
      of ischemic myocardium, prevent the decrease of pH of coronary sinus blood, thus
      myocardial cell acidosis was prevented, myocardial contractile force was
      strengthened. It might be the mechanism of acupuncture treating coronary heart
      disease.

PMID- 1394953
TI  - [Effect of electroacupuncture point on the value of ventricular fibrillation
      threshold in rats].
AB  - The Neiguan and Lingdao were stimulated by electroacupuncture in anesthetized
      Wistar rats. We observed that the value of ventricular fibrillation threshold
      (VFT) was increased significantly in 30 min of electro-acupuncturing (P less than
      0.01) and in 15 min of stopping the acupuncturing (P less than 0.05). Although
      the value of VFT was increased until 30 min of stopping acupuncture, it was not
      significantly different compared with its basic value. The control group were
      dealt with the same way as the experimental group except electroacupuncture. The
      value of VFT measured in control group were not significantly different compared
      with its basic value.

PMID- 1394954
TI  - [The role of ear electroacupuncture on arterial pressure and respiration during
      asphyxia in rabbits].
AB  - This paper reports the study of the effect of ear electroacupuncture (EA)
      inserted in the "Er Jian" point on arterial pressure and integrated phrenic nerve
      discharge (IPND). The result showed that the arterial pressure was decreased and
      frequency of IPND was increased. The differences as follows: During spontaneous
      breathing, the blood pressure and IPND were -36.56 +/- 26.63 mmHg and, 2.42 +/-
      1.42 spikes/10S (P less than 0.001); in excitatory period, -24.31 +/- 6.01 mmHg
      and, 2.16 +/- 1.12 spikes/10S (P less than 0.01) and in inhibitory period -18.26
      +/- 7.04 mmHg (P less than 0.01) and, 2.07 +/- 1.07 spikes/10S (P less than
      0.05). The lasting time was 26 min, 330S and 280S. We observed 20 cases with
      hypertension by ear electro-acupuncture. The systolic pressure and diastolic
      pressure of hypertension patients were decreased (P less than 0.001) and
      respiratory rate increased (P less than 0.05).

PMID- 1394955
TI  - [A study on the effect of stimulating auricular points on the biliary tract].
AB  - We have developed an animal model to study the effect of stimulating auricular
      points on the function of hepato-biliary system. The preliminary result shows
      that 14 of 18 rabbits acquired a marked increase (P less than 0.05) in the amount
      of heptic bile secretion 3 min and 7 min after point No. 3 stimulated with 58V.

PMID- 1394956
TI  - [The effect of electroacupuncture "zusanli" and "neiguan" points on membrane
      fluidity of red cells in rabbits].
AB  - The effect of electroacupuncture "ZUSANLI" and "NEIGUAN" points on membrane
      fluidity of red cells in rabbits, has been determined by fluorescence
      polarization method. Results showed that the membrane fluidity of red cells was
      developed evidently after electro-acupunctured "NEIGUAN", but "ZUSANLI" had no
      effect on it, and it was significantly developed by electroacupuncture "ZUSANLI"
      and "NEIGUAN" points at the same time.

PMID- 1394957
TI  - [The role of peripheral C afferent fiber in electroacupuncture analgesia].
AB  - Experiments were carried out in rats anaesthetized with urethane (1 g/kg). Late
      discharges of spinal dorsal horn neurons were recorded as noxious responses to
      strong stimulation of right tibial nerve (a train of 3 pulses, 25V, 1ms). Left
      St.36 and Sp.6 were stimulated electrically (100Hz, 3V or 6V, 1ms). Left sciatic
      nerve was exposed and soaked for 15 min in 1.5% capsaicin or vehicle 24 hours
      before experiment. Left femoral nerve was sectioned. Spinal cord was transected
      at T4 level in spinal rat. Intact rats: 1) EA group (N = 12). Sciatic nerve was
      not treated. Late discharges of neuron were reduced to 44.6 +/- 18.3% of control
      (P less than 0.02) by EA(3v). 2) Capsaicin group (N = 15). Late discharges were
      reduced to 89.8 +/- 6.0% of control (P greater than 0.05) by EA(3V). 3) Vehicle
      group (N = 10). Late discharges were reduced to 51.2 +/- 15.6% of control (P less
      than 0.05) by EA(3V). 4) There was a statistical difference (P less than 0.05)
      between capsaicin and vehicle group. Spinal rats: 1) EA group. Late discharges of
      neuron were reduced to 67.6 +/- 10.3% of control (P less than 0.02) in 11 neurons
      by EA(3V), 72.7 +/- 8.8% (P less than 0.01) in 9 neurons by EA(6V). 2) Capsaicin
      group. Late discharges were 110 +/- 21.0% of control (P greater than 0.05) in 13
      neurons after termination of EA (3V), 90.7 +/- 12.9% (P greater than 0.05) in 10
      neurons after EA (6V). 3) Vehicle group. Late discharges were reduced to 67.7 +/-
      8.1% of control (P less than 0.02) in 12 neurons by EA (3V), 68.1 +/- 5.0% (P
      less than 0.01) in 10 neurons by EA (6V). 4) There was a statistical difference
      (P less than 0.05) between capsaicin and vehicle group for 3V, no statistical
      difference (P greater than 0.05) for 6V. C fiber of peripheral nerve is main
      component involved in effect of EA analgesia in intact rats. Both A and C fiber
      of peripheral nerve involved in effect of EA analgesia in spinal rats.

PMID- 1394958
TI  - [Effect of He-Ne laser acupuncture on lymph-nodes in rats].
AB  - The lymphocytes and antigen presenting cells in lymph node of rats stimulated by
      He-Ne laser acupuncture were observed by using TEM and SEM to investigate the
      ultrastructural changes of them. There were numerous activated T-cells which
      showed deeply indented nucleus, abundant small void mitochondria and free
      ribosomes in the paracortex area. The B-cells were gradually differentiated into
      large lymphocytes, immature and mature plasmatic cells which with a lot of rough
      endoplasmic reticulum. They were prominently increased in the pulp area. The
      macrophages had short processes with numerous folds and microvilli and tended to
      neighboring lymphocytes. The nucleus pores were increased. There were a lot of
      pinocytosomes, phagosomes, lysosomes in various size of macrophages. The bundles
      (5-6 nm in diameter) of microfilaments of the macrophages were extended from the
      cytoplasm to the processes. The interdigitating cells which contained the
      characterized single layer of rER, numerous polysomes, mitochondria and well
      developed Golgi-complex were closed to macrophages and lymphocytes. In conclusion
      the activities of the cellular immunity and humoral immunity were enhanced by
      laser.

PMID- 1394959
TI  - [The method of elimination of stimulus artifact distorting action potential
      recorded on peripheral nerve].

PMID- 1394960
TI  - [The influence of different acupuncture manipulations on the plethysmogram of the
      patient with kidney deficiency].
AB  - In order to prove the specific property between the tonifying manipulation (TM)
      and reducing manipulation (RM), and search further for the key in improving the
      effect of manipulation, the influence of to on two different manipulations. The
      plethysmogram in the same body-condition (kidney-deficiency) One was TM with slow
      trusting and quick lefting; the other was RM with the converse movement.
      Randomized block design, cross-over design and single-blind design were used. The
      result showed that the TM increased the amplitude of the plethysmogram obviously,
      whereas the RM had no significant influence on it. There was significant
      difference not only between the TM group and the central group, but also between
      the TM group and RM group (P less than 0.01 or P less than 0.05). The difference
      between the RM group and the control group was not significant (P greater than
      0.05). Meanwhile, it was recommended that "mind concentration" on acupuncture
      manipulation is important. In conclusion, the experiment demonstrated the
      experimental evidence for explaining the mechanism of TM and RM. It was suggested
      that acupuncture manipulations are worthy to pay attention so as to improve
      clinical effect.

PMID- 1394961
TI  - [Electron microscopic observation on the effect of electroacupuncture (EA) on the
      ultrastructure of nucleus raphe dorsalis (NRD) in rats].
AB  - Nucleus raphe dorsalis (NRD) plays an important role in acupuncture analgesia.
      The aim of this investigation is to determine the effects of electroacupuncture
      (EA) analgesia on the ultrastructure of NRD. 12 Wistar rats (220-250g) were
      divided into control and experiment groups. Pain threshold was determined by
      potassium iontophoretic colorimetry. EA was applied at bilateral "Zusanli"
      points. The effective analgesia animals and control animals were sacrificed and
      the NRD were taken out for electron microscopic observation. In EA analgesia
      groups, NRD was observed the number of the clear round vesicle-containing
      terminals and clear round vesicles with the granular vesicle-containing terminals
      showed a significant decrease and sometimes vesicles were emptied. The area of
      presynaptic terminals were expanded. Some synaptic gaps appeared narrow profiles.
      Part of the mitochondria and endoplasmic reticulum in neuron and neurogliocytes
      appeared the expanded profiles. These ultrastructural change of the NRD in EA
      analgesia might indicate the neurons and neurogliocytes were in active functional
      state.

PMID- 1394962
TI  - [Preliminary observation of imaging of facial temperature along meridians].
AB  - Visualization of meridians has been carried out by means of infrared thermography
      and radionuclide scintigraphy, but real success was hardly achieved on some
      special regions including facial channels. In this paper, we would represent some
      imagings of thermal line along channels by means of infrared thermography.
      Distribution of the facial temperature in 139 cases of healthy volunteers and 305
      cases of patients with facial paralysis was observed with model AGA-782 infrared
      thermovision and TC-800 computer. In all cases of patients and 15 cases of
      healthy persons, acupuncture test was conducted. Special program, DISCO3.1 was
      used to process the thermographic data and the results were as follows: 1. Facial
      thermal line along channel was presented in 95 out of 444 cases. High temperature
      line along bladder channel appeared in 34 cases of them; 2. In 26 out of 95
      cases, the thermal line appeared after acupuncture, which could improve the
      imaging of the line; 3. The range of the temperature was within 1.3 degrees C, in
      some cases only 0.2-0.3 degrees C, with +/- 0.5-1.0 degrees C difference to
      surrounding temperature; the width of the line was 1-1.5 cm in most cases; 4. The
      line could appear stably, in some cases, last for several days, weeks or months;
      5. Certain relationship between the appearing of the line and facial paralysis
      was found. As mentioned above, the thermal characteristics of meridians in face
      could be visualized by means of infrared thermography, the special imaging of
      facial temperature along bladder meridian was easily found, related to facial
      troubles and promoted by acupuncture.

PMID- 1394963
TI  - [Preliminary observation on the relation among needling sensation, propagated
      sensation along meridian (PSM), and acupuncture effect when acupuncture neiguan].
AB  - This paper reports 300 coronary heart disease patients with different needling
      sensations, mainly with distension, when acupuncturing Neiguan by identical
      acupuncture doctor with same manipulation. The higher rate of PSM appearance and
      better acupuncture effect were observed, in patients with compound sensation,
      such as sourness-distension and distension-numbness. All of the patients who felt
      pain did not appear PSM and the acupuncture effect was poor. The appearance rate
      of PSM and acupuncture effect of other kind needling sensations were between the
      two. The results showed the kind of needling sensation while acupuncture had
      close relation with the appearance of PSM and the acupuncture effect.

PMID- 1394964
TI  - Expression of inherent neuronal shape characteristics after transient sensitivity
      to epigenetic factors.
AB  - We investigated effects of different substrates and culture media on the early
      morphological differentiation of rat neocortical neurons in culture. In
      particular, we examined the effects of homotypic astrocytes, the adhesive
      glycoprotein laminin and the polycationic substrate poly-L-lysine, as well as
      diffusible astrocyte-derived conditioned medium factors and serum on (1) soma
      area, (2) total neuron area and (3) primary neurite number. To assess variations
      in morphological reactions of neurons with a defined neurotransmitter phenotype,
      we analyzed the differentiation of GABAergic neurons. The morphology of young
      neocortical neurons was dramatically affected by both substrate and culture
      medium. Replacement of the astrocytic monolayer or the astrocyte-conditioned
      medium by other substrates or non-conditioned medium, respectively, was
      accompanied by (1) spreading and flattening of neuronal somata, (2) a marked
      decrease in total neuron area and (3) an increase in the number of primary
      neurites. The various morphological parameters studied exhibited different
      sensitivities to changes of these external factors. Moreover, the influences of
      epigenetic factors on the generation of primary neurites depended on the
      transmitter phenotype of the neuron. The induced morphological alterations were
      transient. At the end of the first week in culture, the surviving neurons
      underwent substantial remodeling of their morphology leading to an expression of
      in vivo shape characteristics. These observations suggest that despite an early,
      transient sensitivity to environmental influences, the neuronal differentiation
      with respect to the morphological parameters studied in culture is to a large
      degree determined by intrinsic factors.

PMID- 1394965
TI  - Pre- and postnatal development of high-affinity [3H]nicotine binding sites in rat
      brain regions: an autoradiographic study.
AB  - The ontogeny of high affinity nicotinic cholinergic binding sites was studied in
      Long-Evans rat brain by in vitro autoradiography, using [3H]nicotine (10 nM) and
      cold (-)nicotine bitartrate to assess specificity. The first binding sites become
      detectable in spinal cord and caudal medulla oblongata at gestational day (GD)
      12. Until GD 14, labelling spreads throughout lower brainstem, mesencephalon and
      parts of diencephalon, with higher densities in ventral areas (including the area
      of developing mesencephalic dopamine neurons). Matrix zones remain unlabelled.
      Receptor sites appear in the cerebellar anlage by GD 15, and in caudal caudate
      putamen by GD 16. During development from late gestational to early postnatal
      stages, labelling is reduced in many lower brainstem areas and increases in
      forebrain, in particular in neocortex. Receptor density remains high in thalamus.
      In neocortex, nicotinic receptor sites are first seen in the subplate layer by GD
      20. Labelling of this zone remains prominent until PN 14, when an additional band
      of increased receptor density is seen in cortical layers III/IV which contain
      high receptor levels in adulthood. At PN 27, the pattern has become similar to
      the adult one. The development of [3H]nicotine-binding sites in individual brain
      regions, with a general caudo-rostral gradient, accompanies cell differentiation
      and early synapse formation, e.g., in neocortex. The ontogenetic pattern differs
      in detail from that of muscarinic-cholinergic binding sites. The early presence
      of binding sites provides a basis for specific actions of nicotine on the fetal
      brain. As a consequence of the ontogenetic changes, different brain structures
      become targets for the action of this drug at different stages of development.

PMID- 1394966
TI  - Administration of tryptophan-enriched diets to pregnant rats retards the
      development of the serotonergic system in their offspring.
AB  - It is well established that an increased availability of tryptophan stimulates
      serotonin synthesis not only in the adult but also in the developing brain. In
      order to study the influence of a permanently increased supply of tryptophan on
      the developing central 5-HT-system, female rats were fed a tryptophan-enriched
      diet from mating throughout pregnancy and lactation. The effect of this dietary
      regime was assessed by measurements of neurochemical markers of 5-HT innervation
      in the developing brain of their offspring. A diminished content of 5-HT, a
      decreased activity of tryptophan hydroxylase and a reduction of crude
      synaptosomal high-affinity 5-HT uptake was found in the cortex and in the brain
      stem of 5 day old rat pups of mothers fed the tryptophan-enriched diet. The
      postnatal increase of all three markers of serotonergic innervation in the
      offspring of these mothers was retarded. Both the initial depletion and the
      delayed maturation of 5-HT content, of tryptophan hydroxylase activity and of
      synaptosomal serotonin uptake were more pronounced in the cortex than in the
      brain stem. Apparently, the increased dietary intake of tryptophan throughout
      pregnancy and lactation caused a delayed outgrowth of 5-HT axons and/or reduced
      collateral sprouting and synapse formation in the brain of the developing
      offspring.

PMID- 1394967
TI  - Expression of the F84.1 glycoprotein in the spinal cord and cranial nerves of the
      developing rat.
AB  - The monoclonal antibody designated as F84.1 was used for an immunohistochemical
      study of the developing rat nervous system. The most prominent neural components
      recognized by F84.1 are motor and sensory components of the spinal cord and
      cranial nerves. F84.1 is first detected in the dorsal root ganglia of embryonic
      day 11 spinal cord. The expression in the dorsal roots persists in the adult. In
      contrast, a more transient expression of F84.1 is found in the spinal motor
      system. F84.1 labels primary neurons of cranial nerves V, VIII, IX and X. F84.1
      is also expressed by the non-neuronal cells of the notochord and the floor plate.
      Immunoprecipitation experiments from several types of cells in culture show that
      the F84.1 antigen is a cell-surface glycoprotein with a molecular weight of 90
      105 kDa. An analysis of the amino terminal sequence demonstrates that the F84.1
      antigen is similar to the chick cell adhesion molecule SC1/DM-GRASP, a member of
      the immunoglobulin superfamily. The pattern of expression of F84.1 in the rat
      differs in several aspects from that of the chick molecules, leaving a
      possibility that F84.1 may be a variant of SC1/DM-GRASP.

PMID- 1394968
TI  - Newly generated neurons of the adult songbird brain become functionally active in
      long-term culture.
AB  - The vocal control nucleus, HVc, of the songbird forebrain undergoes neurogenesis
      in adulthood, as ventricular zone precursor cells divide and their daughter cells
      migrate into the subjacent forebrain, where they differentiate into neurons. We
      have previously demonstrated that the migration and development of these new
      neurons can proceed in vitro, in HVc ventricular zone explant cultures derived
      from the adult canary HVc. By a combination of electron microscopy and
      electrophysiology, we now report that these newly produced neurons become
      functionally mature and synaptically competent in culture. These cells developed
      synaptic contacts which became morphologically evident during the second week in
      culture, and which preceded the development of both stimulus-evoked and
      spontaneous action potentials during the second and third weeks in vitro. Thus,
      the newly generated neurons of the adult avian forebrain can form structurally
      complex, electrically interactive networks in long-term culture.

PMID- 1394969
TI  - Altered development of basal and forskolin-stimulated adenylate cyclase activity
      in brain regions of rats exposed to nicotine prenatally.
AB  - Exposure of the fetus to nicotine is known to affect cellular development,
      synaptogenesis and synaptic activity of a wide variety of neurotransmitter
      pathways in the central nervous system. In the current study, pregnant rats
      received nicotine infusions of 6 mg/kg/day throughout gestation, administered by
      osmotic minipumps. After birth, offspring of the nicotine infused dams displayed
      marked alterations in membrane-associated adenylate cyclase activity; the
      regional selectivity correlated both with nicotinic cholinergic receptor
      concentration and the maturational timetable of each region. In the midbrain and
      brainstem, which display relatively high receptor concentrations and earliest
      cell development, basal adenylate cyclase activity in the nicotine group was
      elevated in the immediate period postpartum, returned to normal by the end of the
      first month, but then became subnormal in young adulthood. The initial promotion
      of basal activity was mirrored by forskolin-stimulated activity, suggesting that
      in this phase, the alterations were occurring at the level of the adenylate
      cyclase catalytic unit itself. The lack of effect on forskolin stimulation in the
      later phase, where basal activity was subnormal in the nicotine group, suggests
      that some alterations in regulatory subunits are responsible for the maturational
      switch in nicotine's effects on adenylate cyclase. In the cerebellum, where cell
      replication occurs primarily after birth and receptor concentrations are low,
      basal adenylate cyclase showed only a deficit in the nicotine group; again,
      although forskolin stimulation was significantly affected, the actions on basal
      activity were much more prominent, suggesting defects at the level of G
      proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1394970
TI  - The immunolocalisation of ubiquitin carboxyl-terminal hydrolase (PGP9.5) in
      developing paraneurons in the rat.
AB  - Protein gene product (PGP9.5) has been detected by means of immunocytochemistry
      in the rat fetus in intra- and extra-adrenal chromaffin cells (E12.5), pancreatic
      islet cells (E12.5), anterior pituitary cells (E14.5), carotid body chief cells
      (E15.5), thyroid C cells (E17.5) and respiratory neuroendocrine bodies (E15.5).
      It was expressed early in ontogenesis coincidental with other known morphological
      and biochemical signs of differentiation.

PMID- 1394971
TI  - Embryonic brain-derived heparan sulfate inhibits cellular membrane binding and
      biological activity of basic fibroblast growth factor.
AB  - We have investigated the ability of glycosaminoglycans from embryonic chick brain
      (15 days old) to interact with basic fibroblast growth factor (bFGF). 35SO4
      metabolically labeled glycosaminoglycans were purified and separated on DEAE
      cellulose chromatography. Material which eluted between 0.20 and 0.35 M NaCl
      displaced the binding of [125I]bFGF to brain membrane. This activity was dose
      dependent and on the basis to its heparinase sensitivity and chondroitinase
      insensitivity, has been attributed to heparan sulfate. CL-6B-Sepharose
      chromatography of this material revealed two glycosaminoglycans of molecular
      masses of about 15,000 and 65,000. Incubation with [125I]bFGF followed or not by
      heparinase and chondroitinase treatment of electrotransfert from SDS-PAGE
      revealed that both of these forms correspond to heparan sulfate chains and bind
      bFGF. In vitro, embryonic brain-derived heparan sulfate inhibited both bFGF
      induced [3H]thymidine incorporation in CCL39 cells and neurite outgrowth in PC12
      cells. These results suggest that heparan sulfate play an important function in
      the control of the biological activity of bFGF during brain development.

PMID- 1394972
TI  - Expression of necdin, an embryonal carcinoma-derived nuclear protein, in
      developing mouse brain.
AB  - Necdin is a polypeptide sequence encoded by neural differentiation-specific mRNA
      derived from embryonal carcinoma cells. We have examined the expression of necdin
      and its mRNA in cultured cells and mouse brain by Northern blot analysis and
      immunohistochemistry. Among various established cell lines including
      neuroblastoma and glioma cells, only differentiated embryonal carcinoma cells
      (P19 and F9) expressed necdin mRNA. Necdin immunoreactivity was localized in the
      nuclei of differentiated neurons derived from P19 cells. Necdin mRNA was detected
      throughout brain regions of adult mouse; the relative abundances in the
      hypothalamus and midbrain were the highest, whereas those in the olfactory bulb
      and cerebellum were the lowest. In developing mouse brain, necdin mRNA was
      expressed during early periods of neuronal generation and differentiation, and
      the peak levels were attained during postnatal days 1-4. Necdin immunoreactivity
      was not detected in the neural stem cells on embryonic day 10, but was
      concentrated in the nuclei of brain cells, mostly neurons, at advanced stages of
      differentiation. The majority of differentiated neurons in the brain had necdin
      immunoreactive nuclei on postnatal day 33. Thus, necdin may represent a valuable
      molecular marker for differentiated neurons both in vitro and in vivo.

PMID- 1394973
TI  - Widespread lateral processes of glial cells in the immature striate cortex of the
      cat.
AB  - The topographies of intrinsic tangential connections of cells in the striate
      cortex of cats were determined in animals ranging in age between 1 day and 30
      days. Implants of the carbocyanin dye, DiI, were found to label cellular elements
      which are classified by morphological criteria as astrocytes, in addition to
      neurons. Labeled astrocytes are seen in all cortical layers and in the
      superficial and deep white matter. Most labeled astrocytes occur underneath the
      DiI implant, but a number of them are also located horizontally at various
      distances from the implant. The horizontal span of the glial processes is the
      same as that for neuronal processes; in contrast to neurons however, the
      laterally distributed astrocytes assume a flat and unclustered distribution in
      the horizontal plane. Our observations suggest that the program for determining
      the span of laterally directed projections in the cat striate cortex is likely to
      be the same for neurons and astrocyte-like neuroglia.

PMID- 1394974
TI  - Effect of milk on dopamine release in the newborn rat: an in vivo microdialysis
      study.
AB  - Newborn rats exhibit a rich behavioral repertoire to access the nipple and obtain
      milk. In older pups, catecholamines including dopamine (DA) mediate the
      behavioral effects of milk. In the present study, pups were delivered at term by
      caesarean section and instrumented with the microdialysis probe. Microdialysis
      samples were collected at 15 min intervals and K(+)-evoked levels of DA were
      measured with HPLC-ED. Pups received either no infusion, single or multiple
      intraoral infusions of saline or milk during subsequent samples. A decrease in
      K(+)-evoked DA release was evident after the first infusion in all subjects.
      Repeated milk infusions continued to reduce levels of extracellular DA, which
      remained evident 30 min after the last milk infusion. The rat neonate's first
      exposure to milk exerts lasting effects on neostriatal DA activity in the absence
      of prior suckling experience.

PMID- 1394975
TI  - Quantifying cadmium and lead in whole blood.

PMID- 1394976
TI  - Serum creatinine as an index of renal function: new insights into old concepts.
AB  - The serum creatinine concentration is widely interpreted as a measure of the
      glomerular filtration rate (GFR) and is used as an index of renal function in
      clinical practice. Glomerular filtration of creatinine, however, is only one of
      the variables that determines its concentration in serum. Alterations in renal
      handling and metabolism of creatinine and methodological interferences in its
      measurement may have a profound impact on the serum concentration of creatinine.
      We review the fundamental principles of physiology, metabolism, and analytical
      chemistry that are necessary to correctly interpret the serum creatinine
      concentration. These principles are then applied to important clinical
      circumstances, including aging, pregnancy, diabetes mellitus, drug
      administration, and acute and chronic renal failure. Despite numerous
      limitations, serum creatinine remains a useful clinical tool, but more accurate
      measures of renal function are frequently necessary.

PMID- 1394977
TI  - Highly sensitive, specific enzyme-linked immunosorbent assay of neopterin and
      biopterin in biological samples.
AB  - An enzyme immunosorbent assay of neopterin and biopterin on a polystyrene
      microtiter plate has been developed. A conjugate of neopterin or biopterin to
      bovine serum albumin was used to raise a specific antiserum against neopterin or
      biopterin in rabbits. An incubation mixture of the antiserum and samples prepared
      from human serum underwent another antigen-antibody reaction with the hapten
      fixed on the microtiter plate. The amount of antibody bound to the fixed hapten,
      which is inverse to the amount of hapten in the sample, was determined by using
      anti-rabbit IgG-horseradish peroxidase conjugate in a usual manner by measuring
      absorbance at 490 nm after reaction with o-phenylenediamine and hydrogen
      peroxide. The minimal detectable amounts of neopterin and biopterin were
      approximately 0.1 pmol. The specificity of the assay was so high that the assay
      system for neopterin completely distinguished it from biopterin, as judged from
      the cross-reaction of 0.002%, and vice versa. The amounts of neopterin and
      biopterin in human serum determined by the present method agreed well with those
      determined by high-performance liquid chromatography. We used the present method
      to determine the concentrations of neopterin in serum from healthy control
      subjects and patients with cancers and systemic lupus erythematosus; the results
      were consistent with literature data.

PMID- 1394979
TI  - Direct, simplified, and sensitive assay of angiotensin II in plasma extracts
      performed with a high-affinity monoclonal antibody.
AB  - A very simple, fast, and sensitive RIA of angiotensin (Ang) II has been
      developed, based on a monoclonal antibody with high affinity and specificity,
      making possible the direct measurement of circulating Ang II in human plasma
      after solid-phase extraction. The purified monoclonal antibody 4D8 has an
      association constant of 1.3 x 10(11) L/mol with Ang II and a cross-reactivity of
      < 1% for Ang I. The assay can detect as little as 0.8 fmol of Ang II in 2 mL of
      plasma and is not influenced by the presence of Ang I. Analytical recoveries
      between 112% and 116% were obtained for Ang II added to human plasma at
      physiological concentrations. Comparison of the RIA with a reversed-phase, high
      performance liquid chromatographic method followed by RIA to measure Ang II in
      human plasma samples from normal and hypertensive subjects--and from normotensive
      subjects before and after an acute inhibition of angiotensin-converting enzyme
      with captopril (50 mg)--showed a high degree of correlation (r2 = 0.93) between
      the two methods.

PMID- 1394978
TI  - Two-site direct immunoassay specific for active renin.
AB  - A sensitive immunoradiometric assay, without an enzymatic step and specific for
      active human renin, was developed with use of two monoclonal antibodies (MAbs).
      In this assay system, the first MAb was coupled to magnetic beads (Magnogel); the
      second one, directed against the active form of the enzyme, was radiolabeled with
      125I. The specificity of this assay was demonstrated in experiments measuring the
      active plasma renin concentration in the presence or absence of inactive renin.
      The assay, performed in two steps, was sensitive enough to detect 0.9 pg of renin
      per tube (3.5 ng/L). Intra- or interassay CVs were < 10%. Concentrations of
      active plasma renin measured in normotensive subjects were between 7 and 40 ng/L.

PMID- 1394980
TI  - Avidin-biotin enzyme immunoassay of osteocalcin in serum or plasma.
AB  - We describe a competitive enzyme immunoassay, the ExtrAvidin-biotin system, for
      determining osteocalcin in human serum or plasma. Antibodies were raised against
      bovine osteocalcin. Binding of the antibodies to osteocalcin was calcium
      dependent. Limit of detection is 0.07 nmol/L (0.4 microgram/L). The standard
      curve for method is linear between 0.3 and 17.6 nmol/L (1.9 and 100
      micrograms/L). Interassay CV over the range 0.9 to 14.8 nmol/L (5.3 to 84
      micrograms/L) is 7.5% to 11.7%. Analytical recovery is 105% +/- 5% (mean +/- SD).
      The measurement, which is adapted to microtiter plates, requires only 20 microL
      of serum and 5 h. The coefficient of correlation between the concentrations
      measured by this method and by a commercially available radioimmunoassay kit (CIS
      Biointernational) is 0.91. Osteocalcin can be measured in serum or heparinized
      plasma. Hemolysis (174 mumol/L hemoglobin) reduces osteocalcin concentration by
      54%. High concentrations of triglycerides (7 mmol/L) give an overestimation of
      63%. Serum concentrations of osteocalcin measured in 130 healthy subjects (ages
      15-64 years) and 86 children (ages 4-14 years) were 1.4 +/- 0.8 and 4.0 +/- 1.5
      nmol/L (8.1 +/- 4.6 and 22.5 +/- 8.6 micrograms/L), respectively (mean +/- SD).

PMID- 1394981
TI  - Sensitive, specific radioimmunoassay for quantifying pergolide in plasma.
AB  - Pergolide, a synthetic ergoline with potent dopaminergic activity, is used to
      treat Parkinson disease. The low plasma concentrations of pergolide achieved
      during therapy complicate the development of a method for its analysis. Because
      radioimmunoassay successfully measures other structurally related ergolines in
      physiological fluids, we undertook the development of a radioimmunoassay of
      pergolide. The detection limit of the radioimmunoassay is 21 ng/L with an optimal
      working range from 100 to 1000 ng/L. We maximized assay specificity by using a
      monoclonal antibody that displayed low cross-reactivity with pergolide sulfoxide,
      a major metabolite found in animals. The radioimmunoassay has performed
      acceptably for > 2 years during toxicology studies with rats and rhesus monkeys
      and in clinical studies involving patients with Parkinson disease. We consider
      the radioimmunoassay a valid method for quantifying therapeutic concentrations of
      pergolide in plasma.

PMID- 1394982
TI  - Spectrotype distributions of circulating IgG from patients with systemic lupus
      erythematosus.
AB  - Pathogenic autoantibodies from patients with systemic lupus erythematosus (SLE)
      may represent a relatively cationic fraction of IgG. We compared the spectrotype
      distributions of affinity-purified IgG from the sera of 10 SLE patients and 10
      age- and sex-matched control subjects. Purified IgG was subjected to isoelectric
      focusing between pI 3 and 9. No significant difference was observed for pI 6.0
      6.5 and 7.5-8.0. However, control subjects had a higher percent of total IgG at
      6.5-7.0 (15.4 +/- 4.0 vs 11.1 +/- 2.0, P = 0.008) and at 7.0-7.5 (22.4 +/- 4.8 vs
      18.2 +/- 3.8, P = 0.04) whereas SLE patients had a higher percent of total IgG at
      8.0-8.5 (24.3 +/- 3.0 vs 20.5 +/- 4.0, P = 0.03) and at 8.5-9.0 (21.9 +/- 5.9 vs
      15.1 +/- 3.7, P = 0.006). Spectrotype distributions of circulating IgG from SLE
      patients are skewed toward higher pI, providing further evidence of proliferation
      of B-cell clones that express more cationic IgG in patients with SLE.
      Longitudinal studies of serum IgG from several patients for > 1 year reveal
      distinct changes in both cationic and anionic clonotypes, suggesting clonal
      expansion of antiidiotypes to autoantibodies.

PMID- 1394983
TI  - Direct determination of cadmium and lead in whole blood by potentiometric
      stripping analysis.
AB  - The commercially available equipment for potentiometric stripping analysis (PSA)
      was tested for routine lead and cadmium determination in whole-blood samples. In
      contrast to anodic stripping voltammetry, PSA is not subject to background
      interferences from organic electroactive constituents in the sample or to the
      presence of dissolved oxygen (i.e., oxygen removal is not necessary). To
      determine lead and cadmium by PSA, it is sufficient to dilute the blood sample
      with an appropriate supporting electrolyte (0.5 mol/L HCl). The detection limit
      changes with deposition time and volume of blood sample used. For 1 mL of blood
      and a 1-min deposition time, the detection limit is 1 microgram/L for both
      elements. If the deposition time increases to 10 min, cadmium can be determined
      at its normal concentration in blood (the detection limit is improved to < 0.1
      microgram/L). Procedures for routine determination of lead and cadmium in whole
      blood are presented.

PMID- 1394984
TI  - Magnesium, total calcium, phosphorus, copper, and zinc in plasma and erythrocytes
      of venous cord blood from infants of diabetic mothers: comparison with a
      reference group by logistic discriminant analysis.
AB  - Concentrations of magnesium (Mg), total calcium (Ca), phosphorus (P), copper
      (Cu), and zinc (Zn) were investigated in plasma (Pl) and erythrocytes (Erc) of
      venous cord blood of 44 infants of diabetic mothers (IDMs). These same
      concentrations plus total glycohemoglobin and fructosamine were determined at
      delivery in a subset of 15 mothers of these infants. Mineral results for IDMs
      were compared with those for 66 apparently healthy newborns. The duration of
      gestation in the two groups was significantly different (P < 0.001). After
      adjustment for gestational age, the mean (+/- SD) differences between groups were
      significant for birth weight, head circumference, Erc-Mg (1.71 +/- 0.17 for IDMs
      vs 1.76 +/- 0.15 mmol/L for control subjects), Pl-Ca (1.96 +/- 0.32 vs 2.48 +/-
      0.22 mmol/L), Pl-P (1.99 +/- 0.40 vs 1.57 +/- 0.25 mmol/L), and Erc-Cu (10.9 +/-
      2.41 vs 12.9 +/- 3.00 mumol/L), but not for Erc-Zn (33.0 +/- 18.3 vs 40.4 +/-
      13.6 mumol/L). The variable that best discriminated between the two infant groups
      after adjustment for gestational age was Pl-Ca. In the 15 mothers, Pl-Mg (0.67 +/
      0.07 mmol/L) and Pl-Ca (1.66 +/- 0.21 mmol/L) concentrations were low, Pl-Zn
      (9.81 +/- 3.40 mumol/L) was normal, and Pl-Cu (33.5 +/- 10.7 mumol/L) was above
      normal. Correlations between total glycohemoglobin and mineral values of the
      mothers or paired IDM mineral values were not significant. The concentration of
      Pl-Ca was positively correlated with Erc-Cu (P < 0.001) and Pl-Cu (P < 0.05) in
      the comparison group newborns but not in the IDMs.

PMID- 1394985
TI  - Analysis for cerebrospinal fluid proteins by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis.
AB  - Cerebrospinal fluid (CSF) proteins with molecular masses of < 150,000 Da were
      identified by immunoblotting after two kinds of nonreducing sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). With PAGE 1 (17-27%
      gradient gel), CSF proteins were clearly separated into seven to nine bands with
      molecular masses of 3000-67,000 Da; seven bands were identified as beta 2
      microglobulin, lysozyme, prealbumin, free kappa and lambda chain, apolipoprotein
      A-I, glycoproteins, and albumin by immunoblotting. With PAGE 2 (10-20% gradient
      gel), proteins were clearly separated into 11-16 bands with molecular masses of
      15,000-150,000 Da; 11 were identified as prealbumin, free kappa and lambda chain,
      apolipoprotein A-I, glycoproteins, albumin, alpha 1-antitrypsin, transferrin
      (separated into two bands), immunoglobulin fragments, haptoglobin, and IgG. We
      analyzed CSF samples collected from 81 patients with cerebrospinal signs by these
      SDS-PAGE methods and observed prominent bands in some cases.

PMID- 1394986
TI  - Precipitation and characterization of an aluminosilicate from AlCl3-Na2SiO3-HCl
      in serum, of interest for Alzheimer disease.
AB  - A precipitation experiment was performed with human serum to model
      aluminosilicate formation in brains of patients with Alzheimer disease. Aluminum
      and (or) silicate ions were added to serum in a 1:2 molar ratio at pH 7.4.
      Precipitates formed immediately and were left for 24 h at 37 degrees C before
      filtration. Silicate and aluminosilicate formed precipitates with human serum
      proteins albumin, transferrin, and IgG. In untreated samples, the IgG/albumin
      ratio increased slightly compared with the ratio in dried serum.
      Diethylbarbiturate-washed precipitates had a significantly lower protein content
      than did untreated ones. The IgG/albumin ratio increased considerably in the
      sample containing aluminosilicate. We conclude that IgG is the sodium dodecyl
      sulfate-soluble human protein most firmly bound to the aluminosilicate matrix.
      From 27Al magic-angle-spinning nuclear magnetic resonance (MAS NMR), a pronounced
      peak was found at 52.79 ppm and a minor peak at 0.53 ppm, suggesting that 4
      coordinated aluminum predominates and that 6-coordinated aluminum is present in a
      smaller proportion. The 29Si MAS NMR spectrum shows a poorly ordered structure.
      The aluminosilicate formed also contains the cations Na+ > K+ > Ca2+ > Mg2+ and
      anions Cl- > PO4(3-). Rather than looking for aluminum toxicity to explain the
      effects of Alzheimer disease, one should consider that by precipitating such a
      composite phase, the balance of cations, anions, and proteins in human serum is
      changing.

PMID- 1394987
TI  - Using changes in attributable risk to predict long-term efficacy of simvastatin
      treatment.
AB  - It is a common perception that coronary heart disease (CHD) deaths will decline
      by 2% for every 1% decrease in serum total cholesterol (TC). We investigated the
      changes in serum TC concentrations obtained with simvastatin, an inhibitor of
      hydroxymethylglutaryl-CoA reductase, in 70 hypercholesterolemic subjects.
      Although simvastatin reduced serum TC concentrations by 30% after 6 months,
      calculations from age- and risk-related TC quintiles show that the absolute
      difference in attributable CHD deaths would be just > 1%. These results are
      reminiscent of the experience from several large prospective primary drug trials
      that demonstrated impressive relative benefit ratios but much smaller absolute
      differences (< 2%) in CHD endpoints between the treated and untreated groups.
      This epidemiologically based approach of assessing efficacy and potential long
      term benefit of a lipid-lowering drug may be more appropriate and potentially
      less misleading than just the percentage change of TC (or other lipoproteins) so
      frequently reported in short-term drug trials.

PMID- 1394988
TI  - Simultaneous quadruple-label fluorometric immunoassay of thyroid-stimulating
      hormone, 17 alpha-hydroxyprogesterone, immunoreactive trypsin, and creatine
      kinase MM isoenzyme in dried blood spots.
AB  - We describe a quadruple-label fluorometric immunoassay for simultaneously
      measuring four analytes: thyroid-stimulating hormone (TSH), 17 alpha
      hydroxyprogesterone (17 alpha-OHP), immunoreactive trypsin (IRT), and creatine
      kinase MM (CK-MM). The assay is based on immunoreagents labeled with four
      different lanthanide ions (Eu3+, Tb3+, Sm3+, and Dy3+), on dissociative
      fluorescence enhancement applying the principle of co-fluorescence, and on time
      resolved fluorometry. The monoclonal anti-alpha-TSH and anti-IRT antibodies and
      the polyclonal anti-CK-MM antibody were labeled with Eu3+, Sm3+, and Dy3+,
      respectively; 17 alpha-OHP was labeled with Tb3+. The assay was performed in
      microtitration strip wells coated with a mixture of monoclonal antibodies against
      beta-TSH, IRT, and CK-MM and a polyclonal goat anti-rabbit IgG for capture of the
      rabbit anti-17 alpha-OHP antibodies. After completion of the immunoreactions, the
      bound fractions of the lanthanides were dissociated into the co-fluorescence
      enhancement solution, creating highly fluorescent chelates. The four lanthanide
      specific signals were subsequently measured in a time-resolved fluorometer. The
      detection limits of the assay were 0.1 mIU/L for TSH, 2 nmol/L for 17 alpha-OHP,
      2 micrograms/L for IRT, and 4 U/L for CK-MM.

PMID- 1394989
TI  - Homologous radioimmunoassay of human osteocalcin.
AB  - Osteocalcin or bone gamma-glutamic acid-containing protein (GLA protein) was
      isolated from human bone and used to develop a homologous radioimmunoassay of
      human osteocalcin. The effect of age on serum osteocalcin was studied in 380
      normal children and adolescents and 330 normal adults. The mean (+/- SD) values
      in adults were higher in men [25 +/- 5 micrograms/L (4.3 +/- 0.8 nmol/L)] than in
      premenopausal women [20 +/- 6 micrograms/L (3.4 +/- 1.0 nmol/L); P < 0.01], but
      both were lower than in postmenopausal women [29 +/- 2 micrograms/L (5.0
      nmol/L)]. The highest concentrations were seen in girls [ages 10-12 years: 99 +/-
      38 micrograms/L (17.0 nmol/L)] and boys [ages 14-16 years: 107 +/- 57
      micrograms/L (18.4 nmol/L)]. These mean values were substantially higher than
      those previously reported for results of heterologous osteocalcin
      radioimmunoassays but the correlation (r = 0.87, n = 77, P < 0.001) between both
      sets of results was excellent. In patients with metabolic bone diseases
      characterized by high or low bone turnover, the increase or decrease in serum
      osteocalcin observed was as expected. This homologous radioimmunoassay of human
      osteocalcin thus reflects bone turnover but reports serum concentrations higher
      than previously suspected.

PMID- 1394990
TI  - Flow-injection analysis for malondialdehyde in plasma with the thiobarbituric
      acid reaction.
AB  - A simple, precise, and rapid method to measure plasma malondialdehyde (MDA) was
      developed by use of solvent extraction--flow-injection analysis. The reagent
      solution, containing thiobarbituric acid (TBA), 5 g/L in 100 mL/L phosphoric
      acid, and extraction solvent (methylisobutyl ketone, MIBK) were propelled with a
      double-plunger micropump at a flow rate of 0.3 mL/min, and 20 microL of sample
      was introduced into the reagent stream. After TBA-MDA reactant was extracted into
      MIBK, the organic phase was continuously separated by a successive phase
      separation system equipped with two phase separators, and the absorbance of the
      TBA-MDA reactant was measured at 532 nm. This approach resulted in excellent
      sensitivity, a CV of < 1.5%, a good correlation with the conventional manual
      method, and a sampling frequency of 7 samples/h, suggesting that this
      semiautomated method is suitable for measuring plasma MDA.

PMID- 1394991
TI  - Improved measurement of low-density-lipoprotein susceptibility to copper-induced
      oxidation: application of a short procedure for isolating low-density
      lipoprotein.
AB  - Low-density-lipoprotein (LDL) oxidation may provide the crucial link between
      plasma LDL and atherosclerotic-lesion formation. Oxidation can be induced in
      vitro by incubating LDL with cells or metal ions and can be measured by
      continuously monitoring conjugated-diene absorbance at 234 nm. Measurement of LDL
      oxidizability was improved by performing the assay with 0.05 g of LDL-protein per
      liter of phosphate buffer containing 1 mumol of EDTA, by initiating oxidation by
      adding CuCl2 (5 mumol/L) at 30 degrees C, and by using a short-run
      ultracentrifugation method for isolating LDL, which reduced the time needed for
      obtaining purified LDL and thus reduced in vitro oxidation. LDL apolipoprotein
      analysis and oxidizability determination showed that this method is better than
      the longer sequential-isolation procedure. Adding butylated hydroxytoluene (BHT)
      to plasma as an antioxidant unpredictably increased the LDL oxidation lag time,
      making BHT unsuitable as an antioxidant. Adding EDTA appeared to be sufficient to
      prevent in vitro oxidation. Additionally, the diene production correlated highly
      with the concentration of thiobarbituric acid-reactive substances (r = 0.97). No
      relation between the vitamin E content of LDL and the oxidation lag time was
      found.

PMID- 1394992
TI  - Automated assay of vitamin B-12 by the Abbott IMx analyzer.
AB  - A nonisotopic assay of vitamin B-12 in human serum or plasma is described,
      performed with the Abbott IMx analyzer. The sample is first treated at pH > 12.5
      to release bound vitamin B-12 and to convert all forms to cyanocobalamin. Next,
      the analyte is bound, at lower pH, by vitamin B-12-specific binding protein,
      immobilized to a solid phase of polymeric microspheres. Detection involves
      monitoring the activity of the tracer enzyme (alkaline phosphatase) coupled to a
      derivative of cyanocobalamin. Total assay precision is 7.9% for vitamin B-12 at
      200 ng/L, 6.6% at 400 ng/L, and 6.7% at 800 ng/L. Assay sensitivity, calculated
      as 2 SD from the zero calibrator, is 37 (+/- 9) ng/L. The dynamic range extends
      to 2000 ng/L. Analytical recovery of 300 and 600 ng/L additions of vitamin B-12
      to sera with basal concentrations of 30-400 ng/L was 102.5%. Results of the assay
      correlated well with those of commercially available radioisotope assays. No
      interference was observed in specimens from patients with pernicious anemia,
      chronic or acute myelogenous leukemia, or renal failure. Cross-reactivity with
      cobinamide (1 g/L) was < 0.00003%. Vitamin B-12 measurements for blood specimens
      drawn into serum, EDTA, or heparinized plasma-collection tubes agreed within 3%.

PMID- 1394994
TI  - Automated determination of fluvoxamine in plasma by column-switching high
      performance liquid chromatography.
AB  - A column-switching system with high-performance liquid-chromatographic separation
      and ultraviolet detection is described for automated determination of fluvoxamine
      in human plasma or serum. Samples were injected and the drug was retained in a
      clean-up column [20 x 4.6 mm (i.d.)] filled with C8 reversed-phase material (10
      micron particles). After unwanted material was washed out, the drug was eluted
      and separated with an analytical chromatography column, 4.6 x 250 mm (i.d.),
      filled with Nucleosil 100 CN (5-micron particles) with an
      acetonitrile:methanol:0.01 mol/L phosphate buffer eluent (188:578:235 by vol) at
      a flow rate of 1.5 mL/min for < 20 min and detected by spectrometry at 214 nm.
      With oxaprotiline as internal standard, fluvoxamine could be easily quantified,
      and it was well separated from endogenous plasma constituents and various
      psychoactive drugs. The detection limit was 10 micrograms/L (31.6 nmol/L), the
      analytical recoveries were 97-100%, and the relationship between drug
      concentration and detector response was linear from 0 to 1000 micrograms/L (3160
      nmol/L). The automated method is suitable for therapeutic monitoring of
      fluvoxamine in the treatment of psychiatric patients.

PMID- 1394993
TI  - Transferrin index: an alternative method for calculating the iron saturation of
      transferrin.
AB  - We surveyed 140 clinical chemistry laboratories in Australia to establish which
      laboratory methods they used to determine serum iron status: 125 measured serum
      iron (Fe), 85 measured transferrin (TRF), 47 measured total iron-binding capacity
      (TIBC), and 14 measured both TRF and TIBC. Of the 55 laboratories routinely
      reporting TRF saturation (TS), 16 calculated TS directly as (Fe/TIBC) x 100, and
      9 used [Fe/(TRF x 2)] x 100. Thirty laboratories measured TRF and converted it to
      an equivalent TIBC concentration; the derived TIBC was then used to calculate TS.
      We measured iron, TIBC, and TRF concentrations in 94 control subjects, 59
      patients with alcoholic liver disease (ALD), and 20 with proven genetic
      hemochromatosis (GH). TS was compared with a transferrin index (TI = Fe/TRF) to
      determine whether both methods were sensitive for GH screening and which method
      gave the fewest false-positive results with discrimination limits of > 55% and >
      1.0, respectively. All GH patients were detected by both TS and TI at these
      limits. One control subject had a TI > 1.0, whereas three control subjects had a
      TS > 55%. Nine patients with ALD had a TI > 1.0 and 11 ALD patients had a TS >
      55%. Some iron-overload patients had lower than expected TS values compared with
      TI, possibly because of ferritin interference in the TIBC assay. Also, the
      precision of the TRF assay was better than that of the TIBC assay: CVs of 1.85
      3.68% vs 6.17%. We therefore recommend that calculated TI replace TS in screening
      for iron overload.

PMID- 1394995
TI  - Serotonin concentrations in plasma and variations during the menstrual cycle.
AB  - We used a specific and sensitive radioenzymatic method to establish a reference
      interval for the concentration of serotonin in platelet-poor plasma in 98 healthy
      volunteers (49 men, 49 women). The interval was 0-11 nmol/L with a median of 2.8
      nmol/L. No difference in concentration in relation to sex or age was observed. In
      a group of eight very old volunteers (ages 86-92 years), however, concentrations
      were increased. In addition, we monitored the plasma concentrations of serotonin
      in 20 healthy women (ages 26-45 years) through two menstrual cycles.
      Periovulatory and premenstrual concentrations were greater than the serotonin
      concentration at the start of menstruation.

PMID- 1394996
TI  - Nonimmunological assay of urinary albumin based on laser-induced fluorescence.
AB  - We describe the first nonimmunological assay of albumin in urine with a detection
      limit of 1 mg/L. The method is simple, rapid, and accurate. It is based on the
      probe Albumin Blue 670, which becomes highly fluorescent on binding to albumin.
      An inexpensive diode laser was used as the light source for measurement of laser
      induced fluorescence. The assay was coupled to a flow-injection analysis system
      capable of running 20 samples per hour. The working range was 1-100 mg/L, which
      covered albumin concentrations found in nonpathological urine and in urine with
      slightly increased albumin. This range makes prediction of nephropathy possible
      at an early stage. Other serum proteins and hemoglobin do not interfere. The
      coefficients of variation were < 4% and < 7% within one day and from day to day,
      respectively. A correlation coefficient of 0.990 (n = 100) was obtained for
      comparison with the Behring nephelometric assay.

PMID- 1394997
TI  - Laboratory evaluation of the Glucocard blood glucose test meter.
AB  - The Glucocard (Kyoto Daiichi Kagaku) blood glucose meter is designed for self
      monitoring of blood glucose concentrations in capillary blood through use of an
      electrochemical test strip. Evaluated in this laboratory, the Glucocard had CVs
      of 4.6%, 6.6%, and 3.5% at blood glucose concentrations of 2.4, 4.1, and 18.9
      mmol/L, respectively. The meter's response varied linearly with blood glucose
      concentration between 2.2 and 27.8 mmol/L. Hemolysis, urate, ascorbate, and
      acetaminophen interfered by > 5%. Different hematocrits, in the range 0.20-0.70,
      did not affect the measured glucose concentration. Comparison with glucose
      results measured in whole blood with a NOVA Stat Profile 5 instrument yielded the
      following: Glucocard = 0.898 NOVA--0.184 (r = 0.995). The main advantages of the
      Glucocard are its small sample volume (5 microL), wide linear range, and fully
      automated sample-handling steps, which reduce user-related variability.

PMID- 1394998
TI  - Axon clinical chemistry analyzer evaluated according to ECCLS protocol.
AB  - We assessed the analytical performance of the Axon system (Bayer Diagnostici),
      according to the European Committee for Clinical Laboratory Standards guidelines,
      for assay of 12 analytes: cholesterol, creatinine, glucose, total protein, urea,
      uric acid, alkaline phosphatase, alpha-amylase, aspartate aminotransferase,
      creatine kinase, sodium, and potassium. The field evaluation lasted approximately
      5 months and involved the collection of approximately 10,000 data points with the
      Axon. The following results were obtained: The highest CVs for controls and human
      sera at different concentration/activity values were 2.2% for within-run
      imprecision (n = 60; 3 days, pooled estimate) and 3.5% for the between-day
      imprecision (n = 20 days). Close correlation was found with results for patients'
      specimens assayed with comparative instruments (Hitachi 717 for substrates and
      enzymes, Beckman Synchron EL/E4A for electrolytes). No drift was observed during
      8 h of operation. The linearity range was broad, sometimes exceeding the
      manufacturer's claims. No sample-, reagent-, or cuvette-related carryover was
      found. Measurement of control sera gave results within +/- 5% of the assigned
      values. We conclude that good reliability and practicability make the Axon system
      suitable for laboratories with various needs.

PMID- 1394999
TI  - Two novel nonradioactive polymerase chain reaction-based assays of dried blood
      spots, genomic DNA, or whole cells for fast, reliable detection of Z and S
      mutations in the alpha 1-antitrypsin gene.
AB  - Two new nonradioactive polymerase chain reaction (PCR)-based assays for the Z and
      S mutations in the alpha 1-antitrypsin gene are presented. The assays take
      advantage of PCR-mediated mutagenesis, creating new diagnostic restriction enzyme
      sites for unambiguous discrimination between test samples from individuals who
      are normal, heterozygous, or homozygous for the mutations. We show that the two
      assays can be performed with purified genomic DNA as well as with boiled blood
      spots. The new assays were validated by parallel testing with a technique in
      which PCR is combined with allele-specific oligonucleotide (ASO) probes. In all
      cases tested the results obtained by the different techniques were in accordance.
      The new assays can be used for prenatal diagnostics and can be performed directly
      with boiled tissue samples. Because the new assays are easy to perform and
      reliable, we conclude that they are well suited for routine diagnosis.

PMID- 1395000
TI  - Standardization with synthetic 22-kDa monomer human growth hormone reduces
      discrepancies between two monoclonal immunoradiometric assay kits.
AB  - Discrepancies among different methods for assaying human growth hormone have been
      described in various studies. The two major sources of discordant results are the
      heterogeneity of the antibodies and the different standardization bases used by
      the assay manufacturers. We propose standardizing assays with 22-kDa biosynthetic
      monomer human growth hormone diluted with the diluents supplied by the kit
      manufacturers. In a study of two monoclonal immunoradiometric assays (Hybritech,
      specific for the 22-kDa monomer; Sorin, recognizing also a 20-kDa variant
      hormone), standardization with 22-kDa monomer human growth hormone reduced by 63%
      the differences in results for 44 serum samples from children. The use of 22-kDa
      human growth hormone as a common standard, highly pure and easily available in
      large quantities, could help limit the interpretative problems in growth
      diagnostics.

PMID- 1395001
TI  - Improving lactate analysis with the YSI 2300 GL: hemolyzing blood samples makes
      results comparable with those for deproteinized whole blood.
AB  - To obviate the well-documented problem of hematocrit dependency of the Yellow
      Springs Instruments (YSI) whole-blood lactate analyzer, we modified the dilution
      buffer by including a lysing reagent. This makes the results comparable with
      those of methods performed with deproteinized whole-blood samples. No
      centrifugation step is needed, thus preserving the convenience of the YSI
      instrument for stat and field use. The modification works equally well on plasma
      samples. Lactate concentrations measured in nonhemolyzed whole blood are not
      comparable with results for hemolyzed whole blood or protein-precipitated whole
      blood. We therefore recommend to all users of YSI equipment to lyse the
      erythrocytes before lactate determinations.

PMID- 1395002
TI  - Cathepsin D concentration in breast cancer cytosols: correlation with disease
      free interval and overall survival.
AB  - Cathepsin D (CD) is an aspartyl protease implicated in cancer metastasis. In this
      study of 331 patients, we show that patients with primary breast carcinomas
      containing high concentrations of CD have a significantly shorter disease-free
      interval (chi-square = 4.28, P < 0.05) and overall survival (chi-square = 7.7, P
      < 0.01) than patients with low concentrations. CD as a prognostic marker for
      overall survival was equally valuable for women younger (chi-square = 4.39, P <
      0.05) and older (chi-square = 3.97, P < 0.05) than 50 years. CD was also a
      significant prognostic marker for overall survival within the estradiol receptor
      (ER)-positive subgroup of patients (chi-square = 5.79, P < 0.025), but not in the
      ER-negative subgroup. Patients with tumors containing high concentrations of CD
      and low concentrations of ER had shorter disease-free intervals (chi-square =
      15.1, P < 0.001) and lower overall survival (chi-square = 20.9, P < 0.001) than
      patients with high concentrations of ER but low concentrations of CD.

PMID- 1395003
TI  - Iohexol in serum determined by capillary electrophoresis.
AB  - Iohexol, a nonionic compound used as a contrast medium for angiography and as a
      measure of the glomerular filtration rate, was quantified in serum by capillary
      electrophoresis. Comparable results were obtained for serum samples deproteinized
      with acetonitrile or analyzed directly after 50-fold dilution with borate buffer.
      Serum samples were electrophoresed for 2.6 min at 12 kV in a borate buffer with
      detection at 254 nm and with 3-isobutyl-1-methylxanthine as internal standard.
      Acetonitrile deproteinization gave a greater sensitivity than did sample
      dilution. Between-run CVs were between 4.7% and 6.7%, and within-run CVs were
      between 2.5 and 3.2%. Analytical recoveries were 95-105%. Results of the method
      compared well with those by high-performance liquid chromatography (slope 0.96,
      intercept 0.005 g/L). This method demonstrates the potential of capillary
      electrophoresis for rapid and simple quantification of small molecules.

PMID- 1395004
TI  - Fluorometric enzyme immunoassay of basic fibroblast growth factor with monoclonal
      antibodies.
AB  - We compared three different strategies for measuring basic fibroblast growth
      factor (bFGF) by fluorometric enzyme immunoassay (EIA). After optimizing
      conditions, we found that a primary anti-bFGF MAb directly conjugated with
      peroxidase gave the best detection limit for recombinant bFGF (approximately 30
      ng/L, 3 pg/assay tube) in a two-site sandwich assay. The detection limit of
      methods based on biotinylated primary MAbs or on secondary antibodies followed by
      streptavidin-conjugated peroxidase was slightly lower than that of the above
      method. Using the most sensitive EIA examined in this study, we made a
      preliminary measurement of immunoreactive bFGF in sera of apparently healthy
      people and found it to be 190 (SD 32) ng/L (n = 48), in agreement with an earlier
      reported value (30-206 ng/L). Also, the concentration of immunoreactive bFGF in
      sera was above normal in 19 of 31 patients with stomach cancer.

PMID- 1395005
TI  - In vitro effects of light on serum bilirubin subfractions measured by high
      performance liquid chromatography: comparison with four routine methods.
AB  - The effects of light on serum bilirubin subfractions in vitro were investigated
      by HPLC and four routine methods for bilirubin analysis. By HPLC, the rate of
      photodegradation of unconjugated bilirubin (Bu) was nearly twice that of
      monoconjugated bilirubin (mBc) and threefold that of diconjugated bilirubin
      (dBc); delta bilirubin (Bd) was most stable against photoirradiation. In the
      diazo method, the rate of photodegradation of direct bilirubin was almost the
      same as that of the sum of mBc, dBc, and Bd determined by the HPLC method.
      However, the rate of photodegradation of indirect bilirubin was significantly
      lower (P < 0.001) than that obtained by HPLC, because approximately 30% of the
      bilirubin photoproducts reacted with the diazo reagent as indirect bilirubin. The
      rate of photodegradation of total bilirubin determined by the direct
      spectrometric method was lower than that determined by the diazo method, but
      equal to that of the total peak areas of HPLC. In the Ektachem method, bilirubin
      photoproducts affected total bilirubin negligibly, and Bc and Bu positively, so
      that the value of Bd decreased. In the bilirubin oxidase method, bilirubin
      photoproducts were oxidized enzymatically by both the total and direct bilirubin
      reagents. We re-emphasize the importance of shielding serum from light to avoid
      generating bilirubin photoproducts that interfere with the accurate determination
      of serum bilirubin subfractions. We also recommend HPLC analysis as a standard
      method for bilirubin measurement.

PMID- 1395006
TI  - Superiority of dynamic over static reference intervals for intact, midmolecule,
      and C-terminal parathyrin in evaluating calcemic disorders.
AB  - We compared the clinical performance of assays of intact, C-terminal, and
      midmolecule parathyrin (PTH), when used with either a dynamic reference interval
      (based on the range of serum PTH concentrations observed in 35 healthy
      individuals during acute modifications of their blood calcium concentrations) or
      a gaussian (mean +/- 2 SD) interval derived from normocalcemic individuals.
      Dynamic intervals were substantially different from gaussian intervals, with half
      of the area delimited by the gaussian limits for calcium and intact PTH
      concentrations, and one-third for both C-terminal and mid-PTH assays, being
      outside the range of values observed during the dynamic tests. Use of the dynamic
      intervals increased the average clinical sensitivity of the three assays for
      detecting primary hyper- and hypoparathyroidism from 68% to 97% (and up to 100%
      for the intact and C-PTH assays). Even though only the intact PTH assay allowed
      complete separation between primary hyperparathyroid and nonparathyroidal
      hypercalcemic patients, the average proportion of patients correctly classified
      in this latter category was increased from 40% to 70% by the use of dynamic
      intervals. We conclude that gaussian reference intervals are largely responsible
      for the poor clinical sensitivity of many types of PTH immunoassays and that they
      should be replaced by dynamic reference intervals when evaluating calcemic
      disorders.

PMID- 1395007
TI  - Concentrations and molecular forms of C-type natriuretic peptide in brain and
      cerebrospinal fluid.
AB  - To develop a radioimmunoassay (RIA) specific for human C-type natriuretic peptide
      (hCNP), we used a highly specific antiserum raised in rabbits. Quantitative
      inhibition tests with various natriuretic peptides demonstrated that the 50%
      inhibitory dose of hCNP was 15 fmol, whereas those of other natriuretic peptides
      were 10(5)-fold higher, indicating a specificity satisfactory for determining
      concentrations of hCNP in tissues. Using this antiserum, we detected
      immunoreactive hCNP (ir-hCNP) in various regions of human brain and spinal cord,
      as well as in cerebrospinal fluid (CSF). The ir-hCNP concentrations in human
      neural tissues were approximately 10-fold higher than those of immunoreactive
      human atrial natriuretic peptide (ir-hANP). The mean (+/- SD) concentration of ir
      hCNP (72.0 +/- 17.8 ng/L) in CSF also was 10-fold higher than that of ir-hANP
      (5.2 +/- 2.1 ng/L). Using gel-permeation chromatography, we identified two
      molecular forms of ir-hCNP in brain and CSF: a 2-kDa form corresponding to mature
      hCNP, which is composed of 22 amino acid residues (hCNP-22), and a 5- to 6-kDa
      form corresponding to an N-terminally extended molecule (hCNP-53). The latter
      form was predominant in brain; the former was the main constituent of hCNP in
      CSF. These results support the hypothesis that hCNP is a major natriuretic
      peptide, is synthesized in human brain, and functions in human central nervous
      tissues.

PMID- 1395008
TI  - Concanavalin A-immobilized glycoprotein antigen for immunoaffinity purification
      of antiserum.

PMID- 1395009
TI  - Intra-individual changes in concentrations of urinary albumin, serum albumin,
      creatinine, and uric acid during normal pregnancy.

PMID- 1395010
TI  - Identification and HPLC analysis of an impurity in estriol 16 alpha-glucuronide.

PMID- 1395012
TI  - Simple, rapid method for determining nitrates and nitrites in biological fluids.

PMID- 1395011
TI  - Water- and salt-loss syndrome in low-weight premature infants: 40 years later.

PMID- 1395013
TI  - Comments on proficiency testing.

PMID- 1395014
TI  - Comments on proficiency testing.

PMID- 1395015
TI  - Bufalin and unidentified substance(s) in traditional Chinese medicine cross-react
      in commercial digoxin assay.

PMID- 1395016
TI  - Radioimmunoassay of gastric inhibitory polypeptide in plasma.

PMID- 1395018
TI  - Pitfalls in measuring lutropin by two-site immunoassay with monoclonal antibodies
      against the intact molecule.

PMID- 1395017
TI  - Controversial results by CA 125 immunoradiometric assay and enzyme-linked
      immunosorbent assay not due to human anti-murine antibody.

PMID- 1395019
TI  - Effects of intravenous infusion of ascorbate on common clinical chemistry tests.

PMID- 1395020
TI  - Squamous cell carcinoma antigen immunoactivity is normal in maternal serum but
      high and increasing in amniotic fluid during pregnancy.

PMID- 1395021
TI  - Determination and assessment of the stability of phenylalanine and tyrosine in
      blood spots by HPLC.

PMID- 1395022
TI  - Testing urine for drugs.

PMID- 1395023
TI  - Structure and genetic engineering of antigens and antibodies: applications in
      immunoassays.

PMID- 1395025
TI  - Routine use of hair root or buccal swab specimens for PCR analysis: advantages
      over using blood.
AB  - We report the use of hair roots and buccal cells as specimens of choice for DNA
      analysis of genetic diseases in a service laboratory. Our protocols using these
      specimen types show superiority to those using blood specimens in the areas of
      collection, transport, storage and overall cost. Our experience using these
      specimen types for 319 cystic fibrosis delta F508 mutation tests and 62 Leber's
      hereditary optic neuroretinopathy mutation tests leads us to recommend that hair
      roots and buccal cells should be evaluated as specimens of first choice when
      developing PCR DNA analysis.

PMID- 1395024
TI  - Increased prostaglandin PGE2 and 6-keto-PGF1 alpha immunoactivity in incubates of
      gastric mucosa and forestomach of nephrectomized rats.
AB  - Prostaglandin E2 (PGE2)- and 6-keto-PGF1 alpha-like immunoactivity was measured
      in incubates of forestomach and gastric corpus mucosa in (a) unoperated rats, (b)
      rats with sham-operation of the kidneys and (c) rats with bilateral nephrectomy.
      In addition the mean ulcer area in the forestomach and gastric mucosa was assayed
      in all three groups of rats. The PGE2- and 6-keto-PGF1 alpha-like immunoactivity
      in gastric mucosa incubates and 6-keto-PGF1 alpha in the forestomach incubates
      was almost the same in unoperated and sham-operated rats. Increased 6-keto-PGF1
      alpha in the forestomach and of PGE2 and 6-keto-PGF1 alpha in the gastric mucosa
      was found in rats with bilateral nephrectomy before gastric lesions were seen. A
      higher mean ulcer area occurred in the forestomach and gastric mucosa 24-48 h
      after bilateral nephrectomy. We conclude, that the increased PGE2- and 6-keto
      PGF1 alpha production by the gastric mucosa and forestomach was associated with
      the loss of normal renal tissue function. Despite the protection of PGE2 and PGI2
      by gastric tissue, gastric lesions nevertheless occur in acute uraemic rats.

PMID- 1395026
TI  - Determination of enterokinase activity by measuring the disappearance of
      trypsinogen.
AB  - An electrophoretic technique for the determination of enterokinase activity is
      described. The natural substrate trypsinogen is hydrolysed in the presence of
      soybean trypsin inhibitor. Under the conditions of assay, neither the trypsin
      inhibitor nor the trypsin-trypsin inhibitor complex are detected. Enterokinase
      activity can be determined in biological materials such as duodenal aspirates
      without any interference from trypsin activity. A significant correlation exists
      between the present technique and a spectrophotometric technique by which the
      liberation of trypsin activity is used to determine enterokinase activity.

PMID- 1395027
TI  - A flow-through system for the determination of salicylate in blood.
AB  - A flow-through system for the determination of salicylate in blood is described.
      It consists of a Clark-type oxygen probe with the enzyme salicylate hydroxylase
      chemically bound to polymer supports. This probe, when inserted into a flow
      through cell in the presence of salicylate, oxygen and NAD(P)H, produced a
      current signal proportional to the concentration of salicylate. Salicylate was
      assayed in the range 10 mumol/l up to 200 mumol/l with a detection limit of 3
      mumol/l. Salicylate analysis was optimized by selecting the appropriate pH,
      buffer, temperature, enzyme immobilization and NAD(P)H concentration. The
      accuracy of this method was evaluated by recovery studies on 15 sera. Analysis of
      salicylate in serum sample was performed by diluting samples thirty fold with
      phosphate buffer to fit the calibration graphs. The response time of the probe
      was 2 min and 6 min was the time to perform a single analysis. Results compared
      with the TDx procedure correlated well.

PMID- 1395028
TI  - Purification and characterisation of antigenic gliadins in coeliac disease.
AB  - Two gliadins, known to be especially antigenic in coeliac disease, were purified
      to homogeneity by a series of ion-exchange chromatography steps. Their N-terminal
      amino acid sequences showed minor differences but clearly classified them as
      gamma-type gliadins. The purified gliadins were further characterised with
      respect to amino acid composition, molecular mass and E1(1%)cm at 276 nm. Based
      on these properties it is suggested that one of them is identical to a gamma-type
      gliadin, earlier characterised by its nucleotide sequence, whereas the other has
      not previously been described. The purification procedure may form the basis for
      the development of a more differentiated analysis of circulating antibodies for
      diagnosis and makes clinical testing of the toxicity of defined gliadin peptides
      feasible.

PMID- 1395030
TI  - Within-subject biological variation of pituitary-ovarian axis hormones and
      desirable imprecision.

PMID- 1395029
TI  - Human urinary protein 1: evidence for identity with the Clara cell protein and
      occurrence in respiratory tract and urogenital secretions.
AB  - Protein 1 (P1), a low mol mass urinary protein of unknown function, has been
      purified, sequenced and quantified in human biological fluids. The molecular
      size, subunit composition and partial amino acid sequence of P1 are similar to
      those of the 10 kDa Clara cell protein (CC10), a lung secretory protein. P1 is
      found in high concentrations in sputum, bronchoalveolar lavages, urine and semen
      of healthy individuals and in urine of some pregnant women. Contrary to what is
      claimed, P1 or CC10 is not a specific and unique product of the lung, but like
      its homologue in rabbits (uteroglobulin) it is also present in urogenital
      secretions. P1 or CC10 may act as a natural immunosuppressor protecting the
      respiratory and urogenital tracts from unwanted inflammatory reactions.

PMID- 1395031
TI  - Expression of CuZn-superoxide dismutase and glutathione peroxidase in
      erythrocytes from diabetic and non-diabetic subjects.

PMID- 1395032
TI  - Screening of glycerol kinase deficiency in patients affected by Duchenne and
      Becker muscular dystrophy.

PMID- 1395033
TI  - Enzyme induction by drugs and toxins.
AB  - Enzyme induction by drugs mostly concerns those enzymes involved in drug
      metabolism: cytochromes P-450, UDP-glucuronosyltransferases, glutathione S
      transferases, gamma-glutamyltransferases and epoxide hydrolases. A large variety
      of molecular forms exists, but not all of them are inducible (e.g. the inducible
      cytochromes P-450 in man are members of family IA, IIA, IIC, IIE, IIIA).
      Induction is most common in the liver, but also occurs in other organs (lung,
      placenta, lymphocytes). Over the past 20 years a relatively small number of drugs
      and environmental chemicals have been identified as enzyme inducers, perhaps
      fewer than early studies suggested. Information on inducing properties must be
      obtained as early as possible during the development of a new drug and made
      available to clinicians and clinical chemists when the drug is marketed. The main
      consequences of enzyme induction are changes in pharmacokinetics of the drug
      itself or of an associated drug. Much progress has been made in methods to
      identify these inducers.

PMID- 1395034
TI  - Alkaline phosphatase as a reporter of cancerous transformation.
AB  - Serum levels of alkaline phosphatase (AP) have been used in the clinical
      evaluation of numerous diseases, including malignancies, for half a century. The
      aberrant expression of AP genes in cancer cells has led to the suggestion that
      APs are oncofetal proteins and thus, could be involved in tumorigenesis. Tumors
      which express these AP isozymes can be broadly divided into two groups: (a) those
      with an enhanced production of an isozyme normally expressed in the tissue
      (eutopic expression) and (b) those showing expression of one or more isozymes not
      identified in the normal tissue (ectopic expression). Moreover, many tumors show
      simultaneous expression of two or more different AP isozymes. In the absence of
      known biological functions of the AP isozymes several different mechanisms
      underlying their expression in tumor cells could explain the findings. In an
      attempt to clarify the function of APs, this laboratory is engaged in the study
      of unique properties of the mammalian APs as possible clues to their function,
      i.e., (a) the phosphatidylinositol glycan attachment of APs to the cytoplasmic
      membrane, (b) the uncompetitive inhibition properties of APs and (c) the
      extracellular matrix binding domain of APs. This laboratory is also undertaking
      the task of targeting each of the mouse AP isozymes by homologous recombination
      to generate mouse models of hypophosphatasia to analyze in detail the in vivo
      consequences of AP isozyme deficiencies.

PMID- 1395035
TI  - Changes in enzyme expression related to differentiation and regulatory factors:
      the acid phosphatase of osteoclasts and other macrophages.
AB  - Human tartrate-resistant Type 5 acid phosphatase is a unique isoenzyme encoded by
      a gene located on chromosome 19. It is a member of a widely-distributed and
      structurally highly-conserved group of iron-containing proteins. It is normally
      expressed in certain tissue macrophages, notably osteoclasts and alveolar
      macrophages, but is virtually absent from the precursor monocytes. Factors which
      enhance or inhibit expression of this specific isoenzyme can be studied in
      monocytes and osteoclasts cultured in vitro. This provides opportunities to
      develop the use of Type 5 acid phosphatase as a reporter of pathophysiological
      events and an essential, though not sufficient, role in bone resorption by
      osteoclasts has been established by such studies.

PMID- 1395036
TI  - Plasmodium falciparum induced perturbations of the erythrocyte antioxidant
      system.
AB  - Erythrocyte antioxidants catalase, superoxide dismutase, reduced glutathione and
      glutathione peroxidase were studied in cells harbouring different growth stages
      of Plasmodium falciparum. Catalase and superoxide dismutase showed significant
      decrease during parasite maturation indicating hampered metabolism of hydrogen
      peroxide and superoxide anions. Glutathione peroxidase also exhibited a downward
      trend during the growth of P. falciparum, while there was a moderate accumulation
      of reduced glutathione. These findings suggest decreased utilization of the
      reduction potential in detoxification of reactive oxygen species. The fall in all
      three antioxidant enzymes studied was highly significant (P less than 0.001) in
      erythrocytes with mature stages of the parasite (trophozoites, schizonts). The
      increased vulnerability of erythrocytes to damage, which parallels the growth
      phases of the parasite emphasizes the need for early treatment of P. falciparum
      malaria to minimise red cell destruction and the resulting anaemia.

PMID- 1395037
TI  - Use of an azo derivative immobilized on an anionic resin for the determination of
      aluminium in water and dialysis fluids.
AB  - We studied the retention of aluminium on Chromotrope-2R immobilized on Amberlite
      IRA-400 resin with a view to the subsequent atomic spectrometric determination of
      the metal. The determinative method thus developed allows the determination of
      aluminium in water and dialysis fluids over the concentration ranges 0.92-19.46
      and 0.37-0.74 mumol/l, respectively.

PMID- 1395038
TI  - Investigation of urea cycle enzyme disorders by 1H-NMR spectroscopy.
AB  - High resolution proton nuclear magnetic resonance spectroscopy (1H-NMR) has been
      used to study patients with inborn errors of the urea cycle to evaluate further
      the diagnostic potential of this technique. The 1H-NMR metabolic profile from the
      urine of patients with citrullinaemia and argininosuccinic aciduria consistently
      demonstrated the presence of the diagnostic metabolites citrulline, N
      acetylcitrulline and argininosuccinate, respectively. The profile from the urine
      of patients with ornithine carbamoyl transferase deficiency, is potentially
      diagnostic, but orotate was only detected in samples from three out of four
      patients. The characteristic fingerprint that each of the metabolites produces is
      unlike that of any other we have seen, including analogues of the metabolites
      which are structurally very similar such as arginine, ornithine and aspartate.
      The level of excretion of the metabolites from the patients with citrullinaemia
      and argininosuccinic aciduria has been well within the range of NMR detection.

PMID- 1395039
TI  - Diagnosis of medium chain acyl CoA dehydrogenase deficiency by measurement of cis
      4-decenoic acid in dried blood spots.
AB  - Using gas chromatography-mass spectrometry (GC-MS), with selected ion monitoring,
      a method for measurement of cis-4-decenoate in dried blood spots was developed.
      Using this assay, the concentration of cis-4-decenoate was determined in blood
      spots taken from a control population, seven children with medium chain acyl CoA
      dehydrogenase (MCAD) deficiency who were well at the time of sample collection
      and an asymptomatic sibling of a child with MCAD deficiency. cis-4-Decenoate was
      elevated, above the control range, in all the children with MCAD deficiency and
      in the previously undiagnosed sibling. It is concluded that measurement of cis-4
      decenoate in dried blood spots provides a reliable and sensitive test for MCAD
      deficiency, that could be used in screening programmes.

PMID- 1395040
TI  - Diagnostic value of adenosine deaminase and lysozyme in tuberculous pleurisy.

PMID- 1395041
TI  - Evaluation of solubilizing agents for 25-hydroxy-vitamin D3 immunoassays.

PMID- 1395042
TI  - Clinical test of renal guanidinoacetic acid metabolism by oral citrulline and
      creatine loading.
AB  - We devised a clinical test of renal metabolism based on the synthesis of
      guanidinoacetic acid from citrulline in the proximal convoluted tubule.
      Intravenous administration of a citrulline/creatine solution to rats with
      modified levels of renal glycine amidinotransferase activity revealed a strong
      correlation (r = 0.921) between this activity and urinary guanidinoacetic acid
      excretion. Citrulline (1.75 g) and creatine (1.50 g) were administered orally to
      healthy individuals and patients with chronic glomerulonephritis. In the healthy
      individuals, urinary guanidinoacetic acid excretion increased 5-fold by 2 h after
      dosing (15.1 +/- 2.2 vs. 2.8 +/- 1.1 mg/h). In the glomerulonephritis patients,
      blood clearance of citrulline decreased as the creatinine clearance decreased and
      urinary guanidinoacetic acid excretion also decreased. Of 56 patients with
      glomerulonephritis or diabetes mellitus, one had increased urinary
      guanidinoacetic acid excretion associated with an excess of adrenal androgens.
      This test appears a useful, noninvasive and simple method for examining the
      metabolic activity of the renal proximal convoluted tubules.

PMID- 1395044
TI  - Diagnostic applications of repetitive DNA sequences.
AB  - The potential, the advantages and the different areas of diagnostic applications
      are discussed for the various categories of repetitive DNA sequences. Since all
      eukaryotes are characterized by genomic redundancy, these sensitive, rapid and
      comparatively simple techniques are revolutionizing many a field of clinical and
      experimental diagnostics.

PMID- 1395043
TI  - Increased superoxide dismutase activity in erythrocytes of children with
      pulmonary hypertension.

PMID- 1395045
TI  - Alterations of purine metabolism in mononuclear cell populations of first degree
      relatives of insulin-dependent diabetic individuals with disturbed glucose
      tolerance.
AB  - In a T lymphocyte and macrophage-depleted mononuclear cell population of the
      peripheral venous blood of 10 of 41 first degree relatives of insulin-dependent
      diabetic individuals who had or had had disturbed glucose tolerance adenine
      uptake rates were significantly increased, the relative adenine incorporation
      rates into the adenine nucleotides, however, were diminished. Values were
      compared with those of 30 controls. In 7 of 9 investigated individuals with
      increased adenine uptake rates antibody-dependent cellular cytotoxicity against
      rat Langerhans islets (ADCC) was increased in the same cell population. In these
      individuals the number of diabetes manifestations was relatively high. Adenine
      uptake rates, ADCC and glucose tolerance changed with time.

PMID- 1395046
TI  - Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and urine of
      primary prostate cancer patients: evidence for reduced pineal activity and
      relevance of urinary determinations.
AB  - The circadian rhythms of melatonin and 6-sulfatoxymelatonin (aMT6s) were analyzed
      in serum and urine of young men (YM, n = 8), of elderly patients with benign
      prostatic hyperplasia (BPH, n = 7) and of patients of similar age with primary
      prostate cancer (PC, n = 9). The data expressed as concentration and in urine
      also as hourly excreted quantity were analyzed chronobiologically by the single
      cosinor method and, subsequently submitted to linear regression analyses.
      Circadian rhythms were detected in all cases except for the excreted quantity of
      melatonin. The circadian patterns of melatonin and aMT6s in serum were very
      similar in the different groups and regression analyses showed close correlations
      between both variables. MESOR and amplitude were significantly depressed in PC
      (40-60%) as compared to BPH and YM indicating that the depression of serum
      melatonin in PC is due to a reduced pineal activity and is not caused by an
      enhanced metabolic degradation in the liver. Acrophases of serum melatonin
      occurred between 01:34 and 03:26 h and of serum aMT6s between 03:58 and 04:35 h.
      Circadian rhythms similar to those of serum melatonin and aMT6s were found in
      urine, particularly for aMT6s excretion as well as melatonin concentration; the
      determination of both parameters in overnight urine samples closely correlated
      with the nocturnal peak of circulating melatonin. These results imply that it is
      feasible to estimate changes in pineal function of prostate cancer patients by
      means of non-invasive determination using urinary melatonin and aMT6s.

PMID- 1395047
TI  - Lipid and apolipoprotein changes after orthotopic liver transplantation for end
      stage liver diseases.
AB  - Orthotopic liver transplantation was performed in 37 patients with different
      endstage liver diseases. Changes in lipid and apolipoprotein concentrations were
      followed daily from day 1 to 20 after surgery and regularly thereafter until 12
      months. When the acute effects of surgery had cleared away, there was a sharp
      drop in HDL-C, apo A-I and A-II from day 1 to 5, a stabilization at their lowest
      values from day 5 to 15 and then a progressive rise. Contrasting with this drop,
      triglycerides, apo B, C-II and C-III increased from day 1 to 5 with variable
      concentrations thereafter. Apo SAA considerably increased early after surgery and
      remained significantly higher than normal in most patients after 12 months. All
      other parameters returned to normal from 3 to 6 months after transplant. The
      mechanism leading to these lipid and apolipoprotein changes are discussed with
      respect to the distant effect of infusions, re-alimentation, immunosuppressive
      therapy and lipoprotein metabolism. The apolipoprotein concentrations appear very
      useful indicators of functional liver recovery.

PMID- 1395048
TI  - Relationships between androgen and estrogen sulfates in breast cyst fluid.
AB  - In 28 breast cyst fluids obtained from 20 patients (age 29-65 years) sodium,
      potassium and the sulfates (S) of estrone (E1), estradiol (E2),
      dehydroepiandrosterone (DHEA) and androsterone (A) were determined. The
      radioimmunoassays (RIA) used were validated for this particular biological fluid.
      According to electrolyte ratio (Na+/K+) the cyst fluids were subdivided into two
      groups: the first with low (less than 3) (n = 16) and the other with high
      (greater than 3) (n = 12) values. Markedly higher steroid sulfate levels were
      observed in the first group, the mean levels being: 147.7 nmol/l, 54.6 nmol/l,
      108.1 mumol/l and 158.0 mumol/l for E1S, E2S, DHEAS and AS respectively. The mean
      levels in the second group were: 13.6 nmol/l, 6.7 nmol/l, 68.8 mumol/l and 33.6
      mumol/l for E1S, E2S, DHEAS and AS, respectively. In the first group only E1S and
      E2S levels were significantly correlated (r = 0.51; P less than 0.05).
      Conversely, the steroid sulfate levels were significantly correlated with each
      other in the group with high electrolyte ratio. These data have confirmed
      preceding results and have clearly shown that breast cyst fluids with low
      electrolyte ratio contain more E2S than the other group. This finding might be
      correlated with the fact that patients with these breast cysts lined by with
      apocrine epithelium may be at a greater risk of breast cancer than those with the
      other type.

PMID- 1395049
TI  - Increased membrane activity of glyceraldehyde 3-phosphate dehydrogenase in
      erythrocytes of patients with homozygous sickle cell anaemia.
AB  - Membrane-bound glyceraldehyde 3-phosphate dehydrogenase activity was measured in
      erythrocytes from 43 patients with sickle cell anaemia, 24 heterozygous and 27
      controls. A significant increase of the activity was found among the patients but
      no such difference was observed between the heterozygous and the control
      individuals. The patients showed nearly non Gaussian distribution of the enzyme
      activity and were subgrouped on the basis of these results, subgroup I had normal
      values and subgroup II showed markedly increased activities. The patients in
      subgroup II had significantly lower blood haemoglobin concentrations and
      significantly higher lactate dehydrogenase activities in serum than subgroup I.
      The subgroups did not differ in blood reticulocyte counts, serum bilirubin, serum
      iron concentrations or band 3 protein content of erythrocyte membranes.

PMID- 1395051
TI  - Comparison of three techniques for the determination of protein content in human
      tears.

PMID- 1395050
TI  - An ELISA method to measure human myoglobin in urine.

PMID- 1395052
TI  - Consequences of applying parametric methods to non-gaussian distributions in the
      validation of analytical results.

PMID- 1395053
TI  - Pattern visual evoked potential luminance and multiple sclerosis.
AB  - Pattern visual evoked potentials (PVEPs) were recorded from 111 patients
      classified as having possible, probable or definite multiple sclerosis. Patients
      were stimulated with a checkerboard pattern using high and low luminances in
      order to test the hypothesis that an attenuated pattern luminance increases the
      detection rate of PVEP abnormalities. With increasing certainty of diagnosis,
      there was a concomitant increase in the incidence of PVEP abnormalities. However,
      there was no evidence that stimulating with a lower luminance pattern enhanced
      the sensitivity of the test. The same findings were also apparent when the
      patient data was analyzed according to the presence or absence of a history of
      optic neuritis or other visual symptoms. It is concluded that, within the
      luminance limits used in this study, the role of varied luminance in detecting
      demyelinating lesions in the optic nerves using the PVEP is minimal, although
      there was some limited evidence that a high level of luminance may be more
      appropriate than a low level.

PMID- 1395054
TI  - Differences in pattern visual evoked potential (PVEP) between hemodialysis and
      peritoneal dialysis patients.
AB  - The visual evoked potential was recorded in peritoneal and hemodialysis patients
      as compared to normal controls. By using the appropriate visual stimulus we were
      able to disclose specific VEP abnormalities for each of the two dialysis groups.
      The dissociation found between the latency of N70 and P100 in peritoneal dialysis
      patients suggests a possible postsynaptic visual abnormality not described
      previously. The correlation between the high serum aluminum and the P100 latency
      of peritoneal dialysis patients requires further investigation.

PMID- 1395055
TI  - Alternating periodic lateralized epileptiform discharges (cerebral bigeminy).
AB  - Periodic lateralized epileptiform discharges (PLEDs) are seen, as a rule,
      following acute brain damage. We presented a 54-year-old diabetic male with
      ischemic coronary disease. Following cardiopulmonary arrest, the patient had a
      particular EEG pattern of PLEDs, characterized by two recurrent discharges. To
      our knowledge, this is the fourth published case of such EEG alteration. All of
      the cases were related to anoxic events.

PMID- 1395056
TI  - The Lennox-Gastaut syndrome: electroencephalographic characteristics, clinical
      correlates, and follow-up studies.
AB  - Electroencephalographic and clinical findings are reported for 100 patients with
      the Lennox-Gastaut (LGS) triad of slow bilateral spike and wave (BSW),
      retardation and multiple seizures. Neurological and mental deficits were
      frequently observed, especially in patients who developed seizures before age 1
      yr. More than half of the patients had focal epileptiform discharges that peaked
      in occurrence at age 4-6 yrs. EEG follow-up showed that background frequency
      slowed when patients developed the LGS pattern, and increased after recovery.
      Only 2 patients developed normal EEGs on follow-up, although 22 patients no
      longer showed the LGS pattern after an average of 3 yrs 3 mos follow-up.

PMID- 1395057
TI  - Surface sphenoidal electrode for recording anterior temporal spikes.
AB  - Spike analysis was performed to determine if surface sphenoidal electrodes were
      suitable substitutes for depth sphenoidal or anterior temporal electrodes in
      outpatient EEG recordings for the diagnosis of complex partial seizures of
      anterior temporal origin. Spike measurements consisted of spike detection rate,
      spike amplitude, and location of maximal amplitude spikes. Depth sphenoidal
      electrodes had the highest yield in these three measurements. Surface sphenoidal
      electrodes did not differ from anterior temporal electrodes in spike detection
      rate and spike amplitude, but the former recorded almost no maximal amplitude
      spikes, while the latter had approximately 30% of the maximal spikes. It is
      concluded that surface sphenoidal electrodes are slightly inferior to anterior
      temporal electrodes, but the differences between them are minimal for practical
      purposes in outpatient EEG recordings.

PMID- 1395058
TI  - Frontal spindle activity that appears in conjunction with nontraumatic diffuse
      encephalopathy.
AB  - This peculiar 11-14 Hz spindle activity appears predominantly in the frontal
      area, and was observed in eight patients with impaired consciousness caused by
      nontraumatic diffuse encephalopathy. Characteristic of this frontal spindle
      activity is its transience and accordance with changes in the arousal level of
      the patient. When the degree of impaired consciousness in the patient was minimal
      and clinically not very apparent, this spindle activity appeared during light
      drowsiness. In lethargic patients, it was observed when the patient's level of
      consciousness rose (e.g. immediately after opening and closing the eyes). These
      frontal spindles disappeared at the onset of Stage 2 sleep, when normal
      physiologic spindle waves that are dominant in the vertex area appeared. A
      paroxysmal discharge was sometimes recorded in association with the frontal
      spindle activity and it disappeared at about the same time as these spindles. The
      prognosis was satisfactory for all patients in whom frontal spindle activity was
      observed; its correlation to spindle coma is also studied.

PMID- 1395059
TI  - Neurophysiologic studies in nightmare sufferers.
AB  - Nightmares have long attracted neurologic and psychiatric attention, yet little
      is known of their pathophysiology. We recorded 17-channel electroencephalograms
      (EEGs), brainstem auditory evoked potentials (BAEPs), long-latency auditory event
      related potentials (AEPs), and overnight cassette sleep EEGs (AEEGs) in 10
      individuals with recurrent nightmares. They were all nocturnal sleepers, took no
      medications, do not abuse alcohol or drugs, and had no known medical or
      psychiatric illnesses. Five patients were being evaluated for other complaints, 3
      reported disturbed nocturnal sleep and daytime sleepiness, and 2 sought attention
      chiefly for nightmares. All 10 patients had normal EEGs and BAEPs. BAEP latencies
      did not differ significantly from control subjects. Latencies and amplitudes of
      AEPs were not significantly different in nightmare sufferers and controls, but
      the former had higher amplitude N100, P160, and N200. Those patients with sleep
      complaints had on overnight AEEG, less sleep, decreased slow-wave sleep, and more
      awakenings than those without sleep complaints, but nightmares did not occur
      during the AEEG recordings.

PMID- 1395060
TI  - The use of growth hormone in adults: a changing scene.

PMID- 1395061
TI  - Are women with polycystic ovary syndrome at special risk for coronary heart
      disease?

PMID- 1395062
TI  - Risk factors for coronary artery disease in lean and obese women with the
      polycystic ovary syndrome.
AB  - OBJECTIVE: The evidence that some women with the polycystic ovary syndrome (PCOS)
      are hyperinsulinaemic has brought into question their risk of developing early
      coronary artery disease. We have focused on three cardiac risk factors which have
      been associated with hyperinsulinaemia by measuring glucose tolerance, fasting
      serum lipid concentrations and blood pressure in women with PCOS. DESIGN:
      Comparison of clinical and biochemical measurements in lean and obese women with
      PCOS and in women with normal ovaries. Determinants of the risk factors for
      coronary artery disease were assessed by multiple regression analysis. PATIENTS:
      One hundred and two women with ultrasound diagnosed PCOS and 19 lean women with
      normal ovaries were studied. Patients were recruited from a reproductive
      endocrine clinic. MEASUREMENTS: Fasting total cholesterol, triglycerides, high
      density lipoproteins (HDL), HDL2, glucose tolerance, fasting and stimulated
      insulin, gonadotrophins, testosterone and androstenedione were measured during a
      2-hour oral glucose tolerance test. Recumbent blood pressure was measured
      automatically. RESULTS: Lean women with PCOS were found to be hyperinsulinaemic
      and have reduced serum HDL and HDL2 concentrations compared to women with normal
      ovaries; serum insulin concentrations correlated positively with plasma glucose
      and blood pressure measurements in multiple regression analysis. Obese women with
      PCOS were in addition found to have higher systolic blood pressure, serum
      triglyceride and plasma glucose concentration than lean women with PCOS and
      controls. CONCLUSIONS: These results support the evidence that hyperinsulinaemic
      women with PCOS have an increased risk of developing cardiovascular disease and
      therefore form a population in whom metabolic screening is advisable.

PMID- 1395063
TI  - How common are polycystic ovaries in normal women and what is their significance
      for the fertility of the population?
AB  - OBJECTIVE: We wished to determine the prevalence of polycystic ovaries (PCO) and
      relate morphological appearance to fertility. DESIGN: We sent postal invitations
      to a random sample of women born in the years 1952-1969 from a list of a single
      Group Practice to attend for reproductive history questionnaire, examination,
      ultrasound scan of the ovaries and hormone measurements within 5 days of the
      onset of menstruation. SUBJECTS: Of 1065 women potentially available for study,
      571 (54%) replied of whom 353 (62%) agreed to participate. One hundred and ninety
      (18%) completed the study, 163 were deferred (57 because of current or very
      recent pregnancy, 106 because of inconvenience at time approached), and 18
      additional women volunteered. MEASUREMENTS: Prevalence of polycystic ovaries,
      ovarian size and morphology, menstrual history, features of androgen excess,
      fertility status, serum hormone levels. RESULTS: The prevalence of PCO was 22%
      (41/190). PCO and non-PCO women were similar with respect to age, body mass
      index, oral contraceptive pill (OCP) usage, acne, and menstrual pattern but
      hirsutism (Ferriman and Gallwey score > 7) was significantly (P = 0.006) more
      frequent among PCO women. Proven prior fertility was the same in PCO (56%) and
      non-PCO (64%) women and an equal proportion in each group had not yet tested
      their fertility. Of those women with previously proven fertility, self-perceived
      difficulty in conception occurred in similar proportions of women with and
      without PCO. Unresolved primary or secondary infertility (2.5-4%) was similar in
      both groups. Ovarian volume (each ovary separately) was larger in women with PCO
      irrespective of current OCP usage. Serum levels of oestradiol and FSH were
      similar in PCO and non-PCO women, but LH was distributed around a higher median
      in PCO women. Median testosterone and androstenedione levels were the same in PCO
      and non-PCO women. CONCLUSIONS: The prevalence of polycystic ovarian morphology
      is high but, in this sample of women, was accompanied by minimal clinical
      manifestations and apparently no deleterious effects on earlier fertility. An
      isolated finding of polycystic ovaries may be a normal variation and should not
      necessarily imply altered fertility potential.

PMID- 1395064
TI  - The IgG subclass distribution of TSH receptor blocking antibodies in primary
      hypothyroidism.
AB  - OBJECTIVE: TSH receptor stimulating antibodies are restricted to the IgG1
      subclass suggesting an oligoclonal origin. We wished to determine whether thyroid
      stimulation blocking antibodies, which also bind to the TSH receptor but may
      cause hypothyroidism, are similarly IgG subclass restricted. DESIGN: Sera
      containing TSH receptor blocking antibody activity were separated into IgG
      subclasses by negative depletion of all other subclasses on affinity columns of
      subclass-specific monoclonal antibodies or protein A as appropriate. PATIENTS:
      Eleven patients from two centres were studied. All had autoimmune hypothyroidism
      and TSH receptor blocking antibodies but no thyroid stimulating antibodies.
      MEASUREMENTS: TSH receptor blocking antibody activity was measured by assessing
      inhibition of TSH-stimulated cAMP production by human thyroid cells (five Israeli
      samples) or by the FRTL-5 rat thyroid cell line (six Korean samples). RESULTS:
      IgG1 was the most important subclass containing TSH receptor blocking antibody
      activity but complete restriction to this subclass was never seen. Clearly
      detectable activity was found in the IgG2 subclass in eight patients, in the IgG3
      subclass in three patients, and in the IgG4 subclass in six patients. The
      percentage recovery of activity in the sum of the separated fractions generally
      corresponded to the activity in whole immunoglobulin, being 117 +/- 66% in the
      nine patients in whom this could be assessed, although in one of these, the
      activities in the sum of the fractions was much higher (284%). CONCLUSIONS:
      Unlike thyroid stimulating antibodies, thyroid stimulation blocking antibodies
      are not subclass restricted and are therefore likely to have a polyclonal origin.
      The IgG subclass distribution of these blocking antibodies resembles that of
      thyroglobulin and thyroid peroxidase antibodies.

PMID- 1395065
TI  - Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary
      hyperparathyroidism before and after surgery.
AB  - OBJECTIVE: Primary hyperparathyroidism (pHPT) is associated with hypertension,
      hyperinsulinaemia, and insulin resistance. The present study investigated the
      causes of these metabolic disturbances by quantifying insulin sensitivity and
      glucose effectiveness, and by assessing the time course of beta-cell insulin
      secretion and hepatic insulin extraction, during a dynamic condition such as
      after an intravenous glucose load. In addition, we evaluated the possible link
      between metabolic disorders and high blood pressure. SUBJECTS: We studied 16
      patients with pHPT, before and 12 weeks after parathyroidectomy; eight of these
      patients were re-evaluated one year after surgery. The control group consisted of
      18 healthy volunteers. DESIGN AND MEASUREMENTS: All subjects underwent an oral
      and a frequently sampled intravenous glucose tolerance test. The data from the
      intravenous glucose tolerance test were analysed by means of the minimal model
      technique which yields relevant parameters to comprehend the metabolic status of
      the single individual. RESULTS: The glucose intolerance condition was
      characterized by a severely impaired insulin sensitivity in pHPT (3.2 +/- 0.5 vs
      9.5 +/- 1.5 x 10(4)/min/(microU/ml) of control subjects; P < 0.001), as well as
      by a reduced glucose effectiveness, (0.02 +/- 0.002 vs 0.03 +/- 0.003/min of
      control subjects; P < 0.04). Total insulin secretion during the 4 hours of the
      test was almost twofold elevated in comparison to the control subjects (32795 +/-
      4769 vs 16864 +/- 1850 pM, P < 0.004) and its basal component significantly
      correlated with the high blood pressure. Hepatic extraction of insulin was
      significantly increased in pHPT (85 +/- 2 vs 76 +/- 2%, P < 0.03), possibly as a
      compensatory mechanism of hypersecretion, which however did not prevent
      peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two
      subgroups with normal and impaired glucose tolerance. The patients with impaired
      glucose tolerance had a significant reduction of first phase insulin response,
      although their basal and stimulated insulin levels were higher. Tissue insulin
      sensitivity and glucose effectiveness did not significantly differ between the
      two subgroups. After surgery, all the biochemical parameters (former
      hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized,
      insulin sensitivity significantly improved (6 +/- 1 x 10(4)/min/(microU/ml), P <
      0.001), whereas glucose effectiveness remained completely unchanged. Basal and
      stimulated insulin responses were insignificantly lowered after surgery, and
      hepatic extraction did not change either. CONCLUSIONS: Patients with pHPT
      exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is
      only partially ameliorated by increased hepatic insulin extraction. After
      surgery, although the biochemical abnormalities were fully reversible, the
      metabolic changes improved only partially.

PMID- 1395066
TI  - Effectiveness of computer-assisted perimetry in the follow-up of patients with
      pituitary microadenoma responsive to medical treatment.
AB  - DESIGN: Patients were studied before and after 1 year of bromocriptine or 6
      months of SMS 201-995 treatment, for prolactinomas or GH-secreting adenomas,
      respectively. PATIENTS: Seventeen patients with intrasellar pituitary tumour (ten
      prolactinomas, all females; seven GH-secreting adenomas, four males and three
      females) and the presence of relative or absolute scotomas, were examined.
      MEASUREMENTS: We used computed tomodensitometry, Goldman perimeter and computer
      assisted perimetry. RESULTS: The patients were divided into three groups
      according to their response to medical treatment as proved by computed
      tomodensitometry which revealed the disappearance of the tumour in four
      prolactinomas (group 1), a reduction > 40% in three prolactinomas and in three
      acromegalics (group 2) and no significant variation in the diameter of the
      adenoma in three prolactinomas and in four acromegalics (group 3). Comparison by
      the paired t-test of the visual fields before and after treatment revealed a
      significant positive change (P < 0.01) for all patients in groups 1 and 2 and for
      one patient in group 3, with disappearance of the scotomas in all cases in group
      1 and in two cases in group 2. Visual field defects were detected by means of the
      Goldman perimeter in only one patient with prolactinoma and in two acromegalics,
      although the computer-assisted perimetry showed that, in 15 out of 17 patients,
      visual impairment was unilateral and in all cases the presence of relative
      scotomas was concentrated in the upper temporal quadrant. The visual defects
      observed with computer-assisted perimetry and the pituitary tumour dimension
      evaluated with computed tomodensitometry did not show significative correlations
      (r = 0.059, P NS). CONCLUSIONS: Computer-assisted perimetry was most useful in
      the diagnosis and follow-up of patients with pituitary adenoma, especially in the
      evaluation of small masses without subjective symptoms of visual loss, when the
      Goldman perimeter does not usually allow us to recognize minimal chiasmatic
      involvements or the improvement of visual field as a result of the medical
      therapy.

PMID- 1395067
TI  - Analysis of trough serum growth hormone concentrations: comparison of an
      immunoradiometric assay and a sensitive ELISA for growth hormone.
AB  - OBJECTIVES: We compared a sensitive assay for GH (ELISA) with a conventional
      immunoradiometric (IRMA) assay with particular reference to the oscillatory
      activity detected by Fourier transformation and the estimation of trough
      concentrations using occupancy analysis. DESIGN: Eight healthy adult male
      volunteers underwent 24-hour profiles during which samples were drawn at 20
      minute intervals. Samples were analysed by an ELISA and an IRMA system.
      MEASUREMENTS: The 24-hour serum GH concentration profiles were subjected to
      Fourier transformation and to occupancy analysis. RESULTS: No additional GH
      periodicities could be determined in the ELISA data other than the well
      documented 180-200-minute periodicity. Median observed concentrations (OC) at 5%
      occupancy were 0.035 mU/l (range 0.004-0.22) for the ELISA and 0.035 mU/l (range
      0.001-0.50) for the IRMA. For all OC parameters, 5, 50 and 95%, there was a good
      correlation between the ELISA and IRMA systems. The mean difference (bias)
      between the ELISA and IRMA were -0.05, -0.28 and -1.40 mU/l at OC values of 5, 50
      and 95% respectively and the standard deviations of the difference at the same OC
      values were 0.10, 0.50 and 1.61 mU/l. CONCLUSION: Although there is a qualitative
      improvement on visual inspection of individual 24-hour serum GH profiles obtained
      using the ELISA system, there is little additional information gained in terms of
      pulse periodicity or occupancy analysis.

PMID- 1395068
TI  - Serum levels of growth hormone-binding protein and insulin-like growth factor-I
      during puberty.
AB  - OBJECTIVE: The aim was to investigate the effect of pubertal development on serum
      levels of growth hormone binding protein (GHBP) and IGF-I, and to study the
      relationship between GHBP levels and height standard deviation score (SDS),
      nutritional state and IGF-I levels. DESIGN AND PATIENTS: The investigation was
      performed on serum samples from 72 healthy adolescents of different pubertal
      stage. Results were compared to those obtained in 46 prepubertal children.
      MEASUREMENTS: Serum levels of GHBP were measured by HPLC gel filtration and IGF-I
      levels were measured by RIA after acid-ethanol extraction. RESULTS: No effect of
      pubertal stage on serum levels of GHBP was found. A positive relationship was
      found between serum levels of GHBP and height SDS (r = 0.38; P < 0.005) and
      weight expressed as percentage of median weight for height age (r = 0.46; P <
      0.0005). Serum levels of IGF-I increased during puberty and were not correlated
      with height SDS or weight for height age. In pubertal subjects, no relationship
      existed between serum levels of GHBP and IGF-I. In prepubertal subjects, however,
      a significantly positive relationship between GHBP and IGF-I levels (r = 0.66; P
      < 0.0005) was found. CONCLUSIONS: Pubertal development does not seem to influence
      serum levels of GHBP. Height SDS and nutritional state are related to the
      concentration of GHBP. Before puberty, the level of GHBP is positively related to
      IGF-I levels; during puberty, however, the increase in serum IGF-I levels is not
      accompanied by changes in the amount of circulating GHBP.

PMID- 1395069
TI  - The sensitivity of growth hormone secretion to medical treatment in acromegalic
      patients: influence of age and sex.
AB  - OBJECTIVE: We investigated the relationship between age, sex, pituitary tumour
      volume, serum GH, PRL and IGF-I levels with the responsiveness of GH to TRH,
      bromocriptine and octreotide in patients with acromegaly. DESIGN: We performed a
      retrospective study. Correlations were determined between all variables using
      univariate regression analysis. PATIENTS: One hundred previously untreated
      acromegalic patients were studied (60 males (age 23-76; mean 49 years) and 40
      females (age 25-83; mean 51 years)). MEASUREMENTS: We studied tumour volume,
      fasting morning circulating levels of GH, PRL and IGF-I, mean 24-hour circulating
      GH levels and the acute GH responses to TRH, bromocriptine and octreotide.
      RESULTS: Tumour size was related to serum and mean 24-hour GH levels, but not to
      IGF-I. Circulating IGF-I and GH levels were related only for the group of
      patients whose fasting and unsuppressed GH level was 80 mU/l (40 micrograms/l) or
      less. Older patients tended to have lower circulating GH and IGF-I levels. There
      was a close similarity in the responsiveness of tumorous GH secretion to TRH,
      bromocriptine and octreotide. An elevated serum PRL level predicted a stronger
      inhibitory response of bromocriptine on GH. The sensitivity of GH release to
      octreotide was highest in elderly (especially male) acromegalics, as well as in
      patients with lower IGF-I levels. CONCLUSIONS: Hormone secretion by GH secreting
      pituitary tumours, as well as circulating IGF-I levels, tend to be lower in
      elderly patients. These tumours are more sensitive to octreotide, especially in
      elderly male patients. This suggests that octreotide might be used especially
      successfully as a primary medical therapy in elderly, male acromegalics.

PMID- 1395070
TI  - Growth hormone secreting pituitary carcinoma: a case report and literature
      review.
AB  - Only five cases of growth hormone secreting pituitary carcinoma have been
      documented. We present a 49-year-old West Indian male with grossly elevated
      plasma growth hormone (760-10,400 mU/l), and a large aggressive pituitary tumour
      that continued to grow despite repeated pituitary surgery, radiotherapy and
      medical therapy (bromocriptine and somatostatin analogue). Thirteen years after
      diagnosis the patient died secondary to left ventricular failure. A post-mortem
      revealed a large locally invasive pituitary tumour, but in addition numerous
      tumour seedlings within the cerebrospinal fluid space, and a solitary
      intraparenchymal tumour deposit within the right temporal lobe, clearly separate
      from the primary tumour. Pituitary carcinoma should be considered in any
      acromegalic with grossly elevated plasma growth hormone levels who fails to
      respond to conventional therapy.

PMID- 1395071
TI  - Pituitary carcinoma.

PMID- 1395072
TI  - Endogenous digitalis-like factors.
AB  - The postulate of a natriuretic factor inhibiting the sodium pump in the kidney
      led to the detection of increased concentrations of endogenous digitalis-like
      factors in blood after salt loading, in essential hypertension, in pregnancy
      induced hypertension and in chronic hypervolaemia. The recent isolation of
      ouabain or a close isomer thereof from human plasma and the demonstration of a
      compound similar if not identical to digoxin in adrenals and human urine shows
      that mammals like non-vertebrates and toads may synthesize cardiac glycosides in
      their adrenals and possibly in hypothalamus. The hypothalamus also forms other
      compounds of unknown structure which bind to the cardiac glycoside receptor site.
      The differential functions of endogenously formed ouabain and of a digoxin-like
      substance are unclear. The detailed knowledge of the physiological role of both
      endogenously formed cardiac glycosides in the regulation of blood pressure has
      still to be worked out.

PMID- 1395073
TI  - Factors associated with acute salt-sensitivity in borderline hypertensive
      patients.
AB  - The acute sensitivity to sodium loading has been investigated in 26 borderline
      hypertensive patients (BHT) undergoing acute i.v. NaCl infusion. Measurements
      included blood pressure (BP), forearm vascular resistance (FVR) and venous
      distensibility (VV30), plasma renin activity (PRA), plasma aldosterone, plasma
      atrial natriuretic factor (ANF), and plasma levels of endogenous Na+/K+ATPase
      inhibitor. Sodium loading was associated with a greater than 8% increase in mean
      BP in 12 patients defined as salt-sensitive (NaCl-SENS) in comparison to salt
      insensitive (NaCl-INSENS) subset. NaCl-SENS patients in comparison to NaCl-INSENS
      exhibited 1) a greater baseline VV30 (2.1 vs 1.4 ml/100 ml; p less than .005),
      and a response to saline characterized by 2) increased FVR (21.4 vs -6.5%; p less
      than .005), 3) blunted PRA suppression (-42 vs -67%; p less than .05), 4) delayed
      ANF response and 5) release of a Na+/K+ATPase inhibitor. Post-loading cumulative
      urinary sodium excretion was reduced in NaCl-SENS borderline hypertensives
      compared to NaCl-INSENS (2.6 vs 3.8 mumol/min/Kg; p less than .05). We conclude
      that acute salt-sensitivity in BHT is characterized by a blunted hormonal
      response to sodium loading which could be responsible of the activation of
      hemodynamic as well as humoral mechanisms leading to progressive blood pressure
      increase.

PMID- 1395074
TI  - An indirect evaluation of the effect of the autonomic nervous system following
      converting enzyme inhibition in hypertension.
AB  - Common carotid blood flow and cold pressor test were evaluated in 16 patients
      with sustained essential hypertension before and after 30 days treatment with the
      converting enzyme inhibitor Enalapril (20 mg). Enalapril decreased blood pressure
      and carotid vascular resistance with no significant change in heart rate. After
      treatment, despite a wide range of the responses, the changes in systolic blood
      pressure to cold test were significantly attenuated, whereas the heart rate
      responses were not. Acute random and double blind administration of either
      Cadralazine or Nitrendipine, two vasodilating drugs which are known to cause an
      activation of the autonomic nervous system, were performed before and after long
      term treatment by Enalapril. Whereas the blood pressure and heart rate responses
      to cold test was unmodified by these compounds before Enalapril treatment,
      significant changes were observed after converting enzyme inhibition: Cadralazine
      reduced the heart rate response whereas Nitrendipine increased it significantly.
      The study provides evidence that converting enzyme inhibition causes sympatho
      inhibitory influences which are principally observed in stress conditions, with
      heterogeneous responses depending on the nature and the type of stimulation.

PMID- 1395075
TI  - Protein kinase C and cell proliferation in spontaneously hypertensive rats.
AB  - Cultured aortic fibroblasts from spontaneously hypertensive rats (SHR) exhibit
      increased proliferation rate compared with cells from normotensive Wistar Kyoto
      (WKY) rats. The present study was designed to investigate whether this growth
      abnormality could be accounted for by alteration in protein kinase C (PKC). The
      enzyme activation by 12-O-tetradecanoyl phorbol 13-acetate (TPA) promoted 3H
      thymidine incorporation which was higher in SHR-derived fibroblasts compared with
      WKY-derived cells. Likewise, 3H-phorbol 12,13-dibutyrate (PDBu) binding to intact
      cells was markedly increased in SHR-derived fibroblasts. These findings suggest a
      difference in PKC activity between the two cell types. In both cell types, serum
      induced 3H-thymidine incorporation was enhanced by PKC down-regulation, which was
      obtained by prolonged treatment of cells with high dose of TPA, whereas it was
      inhibited in a dose-dependent manner by activation of the enzyme. The changes in
      serum-induced 3H-thymidine incorporation elicited either by activation or
      desensitization of PKC, did not differ between SHR and WKY fibroblasts. Our
      results indicate therefore i) that in the presence of serum PKC exerts an
      antiproliferative effect in rat aortic fibroblasts and ii) that the increase in
      PKC activity and in sensitivity to TPA exhibited by SHR-derived fibroblasts, is
      not involved in the increased proliferation rate displayed by SHR-derived
      fibroblasts in serum-containing medium.

PMID- 1395076
TI  - Hormonal aspects of the relation of liver cirrhosis to essential hypertension.
AB  - The association of liver cirrhosis with arterial essential hypertension has been
      previously described. The present study extends the previous reports by
      investigating the hormonal relationships that may occur in patients with
      established essential hypertension associated to liver cirrhosis. We studied the
      renin-angiotensin, the adrenergic systems and other vasoactive hormones such as
      arginine-vasopressin, atrial natriuretic peptide, endothelin and parathyroid
      hormone in cirrhotic patients with and without essential hypertension. The data
      suggested that the coincidence of arterial hypertension in cirrhotic patients was
      characterized by the following findings: a decreased renin-angiotensin activity;
      a reduced systemic vasodilatation; an increased peripheral pressor effect of
      vasoactive hormones and an increased effective blood volume.

PMID- 1395077
TI  - Haemodynamic and metabolic effects of short term administration of synthetic sex
      steroids in humans.
AB  - Synthetic sex steroid administration is a major cause of iatrogenic hypertension
      but little is known of the haemodynamic or metabolic consequences of these
      steroids. This study examined the short term blood pressure, volume and metabolic
      consequences of 5 day administration of synthetic androgen to normal men and
      synthetic oestrogen or progestogen to normal women. Healthy subjects (8 women, 6
      men) on a constant diet took part in each of 3 studies. Males received
      testosterone undecanoate 120 mg/day (n = 6) and females either ethinyloestradiol
      0.3 mg/day (n = 5) or norethisterone 15 mg/day (n = 6) for 5 days in the last
      week of the cycle. Norethisterone increased lying (+7 mmHg) and standing (+8
      mmHg) systolic pressure but the other steroids did not alter blood pressure. All
      3 treatments increased body weight. There were no consistent changes in plasma
      electrolytes or glucose with any steroid, and no urinary sodium retention or
      changes in urine Na:K ratio. Haematocrit fell on ethinyloestradiol but no steroid
      significantly increased plasma volume (measured as volume of distribution of 125I
      human serum albumin). Renin substrate and cortisol rose and renin concentration
      fell on ethinyloestradiol. These studies suggest that the progestogen component
      may contribute to the blood pressure raising effects of oral contraceptives.

PMID- 1395078
TI  - Renal renin secretion rate and norepinephrine secretion rate in response to
      centrally administered angiotensin-II: role of the medial basal forebrain.
AB  - The influence that centrally administered angiotensin-II (ANG-II) and saralasin
      (SAR) has on renal norepinephrine secretion rate (NESR) and renal renin secretion
      rate (RSR) were studied. Rats were given thermal lesions of the medial basal
      forebrain (MBF) or sham surgery. Twenty-four hours later the right kidney was
      vascularly isolated (but neurally intact) and perfused with an artificial plasma
      at either a constant pressure (100 mm Hg) or constant flow (600 microliters/min).
      Renal perfusate was collected before (pre-injection) and at 10 min intervals
      after central administration of peptides for determination of NESR and RSR. In
      both perfusion models, intracerebroventricular (ICV) ANG-II increased renal NESR.
      In MBF lesioned rats pre-injection renal NESR is reduced and the response to ICV
      ANG-II is blocked. In both perfusion models ICV ANG-II decreases renal RSR.
      Concomitant administration of SAR blocks the effect of ANG-II on both NESR and
      RSR. MBF lesioned rats had significantly elevated pre-injection levels of RSR and
      there is no change in RSR following ICV ANG-II. These experiments indicate that
      centrally administered ANG-II increases renal NESR concomitant with a decrease in
      renal RSR and that MBF lesions block those changes.

PMID- 1395079
TI  - Putative monosomy 21 in two patients: clinical findings and investigation using
      fluorescence in situ hybridization.
AB  - Complete monosomy 21 is claimed to be a rare chromosomal disorder in which the
      cytogenetic investigation is bedevilled by technical difficulties. We describe
      the disparate clinical features in two patients in whom an initial diagnosis of
      monosomy 21 was made by routine karyotyping. Fluorescence in situ hybridisation
      (FISH) confirmed a translocation of chromosome 21 material to the short arm of
      chromosome 5 and to the X chromosome, respectively. The usefulness of FISH in the
      investigation of subtle chromosomal rearrangements is hereby demonstrated. These
      findings also cast doubt on the existence of "pure" monosomy 21 as an entity, and
      suggest that partial monosomy 21 is a more likely occurrence.

PMID- 1395080
TI  - Congenital hypoparathyroidism, seizure, extreme growth failure with developmental
      delay and dysmorphic features--another case of this new syndrome.
AB  - A 4-year-old Saudi female child with extreme failure to thrive, striking
      dysmorphic features, developmental delay, congenital hypoparathyroidism, UTI,
      seizures, chronic otitis media, chronic non-specific gastroenteritis and repeated
      life-threatening infections was followed from birth. She was the product of first
      cousin consanguineous marriage. She had striking facies with frontal prominence,
      deep-set eyes, depressed nasal bridge, beaked nose, long philtrum with thin upper
      lip, micrognathia, large floppy ears, bifid uvula, and growth retardation with SD
      score less than -2 for height, weight and head circumference. We believe these
      features which include congenital hypoparathyroidism, severe growth failure and
      developmental delay in the absence of chromosomal abnormality represent a newly
      described genetically determined syndrome.

PMID- 1395081
TI  - X chromosome inactivation patterns in haematopoietic cells of female carriers of
      X-linked severe combined immunodeficiency determined by methylation analysis at
      the hypervariable DXS255 locus.
AB  - The patterns of X chromosome inactivation were determined in 14 females from
      three unrelated X-linked severe combined immunodeficiency (XSCID) pedigrees. All
      the females were found to be heterozygous for the hypervariable DXS255 locus,
      enabling analysis of differential methylation of this locus in peripheral blood
      haematopoietic cells. All six obligate carriers manifested a unilateral X
      chromosome inactivation in the T lymphocyte population. Differential methylation
      analysis of T lymphocytes was subsequently applied to establish the carrier
      status of females at risk in the XSCID pedigrees. In the B lymphocyte population
      of four XSCID carriers a unilateral X chromosome inactivation was observed. Four
      other carriers had minor fractions and one carrier had a substantial fraction of
      B lymphocytes with the XSCID gene defect on the active X chromosome. Within
      single XSCID pedigrees the carriers manifested different patterns. In two
      pedigrees the granulocyte populations of all carriers showed a random
      distribution of X chromosome inactivation. In the third pedigree the granulocytes
      of the three carriers analyzed manifested complete inactivation of the X
      chromosome that carried the XSCID mutation, exposing a selective disadvantage of
      granulocytes that express the XSCID defect. The pedigree-dependent differences in
      the involvement of the granulocyte population suggest the existence of two
      distinct XSCID defects.

PMID- 1395082
TI  - Prevalence of retinitis pigmentosa in Slovenia.
AB  - Two hundred and twenty-nine symptomatic patients with retinitis pigmentosa were
      ascertained in Slovenia between 1986 and 1990. Twenty-three further patients were
      identified while data from 63 families (82 patients) were being collected. After
      correction for underascertainment, a prevalence of 1 in 6023 was estimated in the
      Slovene population (1,999,477 in 1990). The highest prevalence of 1 in 1902 was
      found in the age group 65 years and older. Of 63 analysed families, 17 (27%)
      showed autosomal dominant, 13 (21%) autosomal recessive, and one family (1.5%) X
      linked inheritance; in 30 families (47.5%) isolated cases were found; and in two
      families the mode of inheritance was impossible to determine.

PMID- 1395083
TI  - Reassessment of a chromosome 12q+ marker by fluorescent in situ hybridization
      (FISH).
AB  - We present a case previously described by Jenkins et al. (1983) as atypical Down
      syndrome (DS). The initial diagnosis was first made on the basis of phenotypic
      and cytogenetic data. This analysis was supported by studies of superoxide
      dismutase (SOD1) activity that maps to band 21q22.1. Results from phenotypic,
      chromosome banding and SOD1 studies suggested a karyotype of 46,XX,-12,+t(12pter
      to 12qter::21q21 to 21q22.?2). Using fluorescent in situ hybridization (FISH) for
      chromosome painting with DNA libraries derived from sorted human chromosomes to
      stain selectively the chromosomes No. 21 and No. 12, we demonstrate that the
      marker chromosome 12q+ has no chromosome 21 content but it is derived from
      chromosome 12.

PMID- 1395084
TI  - Leber hereditary optic neuropathy: estimation of number of embryonic precursor
      cells and disease threshold in heterozygous affected females at the X-linked
      locus.
AB  - LHON has been suggested to involve both mitochondrial and X-chromosome-linked
      loci. By extending two-locus mitochondrial and nuclear gene analytic methods, we
      recently proposed that a proportion of affected females are likely heterozygous
      at the X-linked locus and affected due to unfortunate X-chromosome inactivation.
      Assuming that the optic tissue is the primary site of action of the mutant
      gene(s), we further propose here that there should be no fewer than six embryonic
      precursor cells for the involved optic tissue at the stage in early development
      when X-chromosome inactivation occurs. We also estimate that the disease
      threshold (i.e. proportion of cells with abnormal X-chromosome active in the
      responsible tissue at the time of X-chromosome inactivation) for a heterozygous
      female is in the range of 0.60 to 0.83.

PMID- 1395085
TI  - Reproductive behaviour following spontaneous loss of pregnancy after prenatal
      diagnosis.
AB  - One hundred and fifty-eight women of advanced maternal age with complete follow
      up who experienced spontaneous fetal loss after prenatal diagnosis were studied
      for reproductive behaviour as well as prenatal diagnosis in a subsequent
      pregnancy. A higher rate of subsequent pregnancies amongst women who experienced
      an early spontaneous abortion after chorionic villus sampling (CVS) was expected
      compared with women who lost a pregnancy later during pregnancy after
      amniocentesis. Of the 92 women who underwent CVS in a previous pregnancy, 57
      (62%) became pregnant again. Of the 66 women who underwent amniocentesis in the
      pregnancy that ended in fetal loss, 34 women (52%) had a subsequent pregnancy.
      The cumulative incidence of subsequent pregnancies was significantly influenced
      by maternal age but not by parity or the method of prenatal testing. Most women
      who decided on a new pregnancy opted for prenatal diagnosis. There was a
      preference for amniocentesis if the patient had previously undergone CVS.
      However, the reverse was not the case.

PMID- 1395086
TI  - Autosomal recessive microcephaly with early onset seizures and spasticity.
AB  - We describe two siblings, a male and a female pair, born of consanguineous
      parents, affected with a rare genetic form of congenital microcephaly. The
      clinical syndrome is characterized by early onset myoclonic seizures, spasticity,
      and profound psychomotor retardation without detectable brain malformations. To
      date, only two kindreds and one sporadic case with a similar clinical picture
      have been observed and reported (Tolmie et al. 1987, Bundey & Griffiths 1977).
      The severity of the neurological features and their perinatal onset differentiate
      the syndrome from the more common autosomal recessive microcephaly with
      spasticity/seizures.

PMID- 1395087
TI  - The gene for Best's macular dystrophy is located at 11q13 in a Swedish family.
AB  - A large Swedish family with more than 250 cases of Best's macular dystrophy has
      been clinically and genetically studied. The gene was traced to a couple born in
      central Sweden in the 17th century. Highly significant evidence for genetic
      linkage to DNA markers on chromosome 11q13 was detected. A lod score of 15.12 was
      obtained at recombination fraction 0.01 with DNA marker INT2 (also called FGF3).
      The retinally expressed gene ROM1, which maps to the same chromosomal region is a
      candidate for this genetic disease.

PMID- 1395088
TI  - Enzyme deficiencies as the cause of hereditary nonspherocytic hemolytic anemia.

PMID- 1395089
TI  - Phospholipid-containing toxic malaria antigens induce hypoglycaemia.
AB  - Hypoglycaemia is associated with severe malaria and is an important prognostic
      indicator. Molecules liberated during overnight incubation of erythrocytes
      infected with Plasmodium yoelii induce marked hypoglycaemia in normal mice, with
      a delayed time course compared with insulin; some, though weaker, activity could
      also be obtained by overnight incubation of uninfected erythrocytes. The active
      component shares many properties with the phospholipid-containing molecules which
      we have previously shown to be toxic and to induce the release of tumour necrosis
      factor (TNF) from macrophages. However a MoAb which neutralizes the cytotoxicity
      of tumour necrosis factor in vitro did not prevent this induction of
      hypoglycaemia, whereas antiserum against the toxic antigens did, as did
      immunization of normal (but not the immunoglobulin-deficient SCID) mice with the
      same material. Furthermore, normal mice injected with the antigens after
      immunization with phosphatidyl inositol or inositol monophosphate did not develop
      hypoglycaemia; the latter compound was also inhibitory when mixed with the
      antigens before injection. These compounds were previously shown to block the
      induction of TNF by the antigens and to induce the production of inhibitory
      antibodies. The role of these molecules in the etiology of the hypoglycaemia of
      malaria is discussed.

PMID- 1395090
TI  - Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of
      disease activity?
AB  - To investigate the possible role of IL-6 in the activation of the autoimmune
      process in systemic lupus erythematosus (SLE), we serially measured
      concentrations of IL-6, IgG, and anti-dsDNA antibodies before and during
      exacerbations in patients with SLE. In addition, we serially related the IL-6
      response to the generation of the acute phase reactant C-reactive protein (CRP).
      Sixteen consecutive patients who developed an exacerbation were analysed in this
      study. Blood samples were drawn in EDTA monthly. At the time of maximal disease
      activity during exacerbation, IL-6 plasma concentrations were increased (greater
      than or equal to 6 pg/ml) in 12 out of the 16 cases. Concentrations of IL-6
      correlated with the concentrations of CRP (P less than 0.01) and the score of the
      disease activity index (P less than 0.05). No correlation was found between IL-6
      concentrations and concentrations of anti-dsDNA or IgG. The course of changes in
      IL-6 concentrations before the exacerbation was variable. Five out of the 16
      exacerbations studied were characterized by a prominent rise of IL-6 at the time
      of maximum disease activity. In this subgroup serositis as well as elevated
      concentrations of CRP were observed more frequently (P less than 0.02). Seven
      exacerbations were not accompanied or preceded by changes in IL-6 concentrations
      and showed generally low IL-6 concentrations. In this latter subgroup cerebral
      involvement was seen more frequently (P less than 0.02). Our data do not suggest
      a pathogenic role for IL-6 in the generation of IgG and/or anti-dsDNA antibodies
      before exacerbations. Rises of IL-6 concentrations before exacerbations in SLE
      seem only to occur in a subgroup of patients with SLE characterized by the
      presence of serositis and elevated concentrations of CRP during exacerbation.

PMID- 1395091
TI  - Hodgkin's cells express a novel pattern of adhesion molecules.
AB  - Adhesion molecules play an important role in the functioning of the immune
      system, particularly with regard to cell-cell interactions and antigen
      presentation. Several adhesion molecules are expressed on Hodgkin's disease
      derived cell lines and these are important in their molecular interactions as
      antigen presenting cells (APC). There are no data regarding the expression of
      many of these adhesion molecules on Reed-Sternberg cells and its mononuclear
      variant (Hodgkin's cells (HC)) present in pathological material. To obtain this
      information we undertook an immunohistological study on material from 18 cases of
      Hodgkin's disease using a panel of MoAbs to examine the expression of adhesion
      molecules on HC. The HC were shown to express the integrin beta 1 subfamily
      molecules, LFA-1 (CD11a) and p150,95 (CD11c) in high density but lacked CR3
      (CD11b). All of the immunoglobulin gene superfamily adhesion molecules studied
      were present to some degree on HC, with ICAM-2, in particular, showing moderate
      to strong expression in most cases. The Hermes antigen CD44 was present in high
      density but leukosialin (CD43), another molecule present on diverse leucocyte
      types, was, in general, not detected on HC. These new data showing that ICAM-1,
      ICAM-2 and LFA-3 are, like LFA-1, expressed on HC emphasize the ability of HC to
      act as APC. The known adhesion molecule phenotype of the recently defined
      haematopoietic lineage of human dendritic cells (DC) is broadly similar to that
      of HC, perhaps supporting the hypothesis that some HC represent a malignancy of
      an APC (DC) lineage.

PMID- 1395092
TI  - Control of immune-mediated disease of the central nervous system requires the use
      of a neuroactive agent: elucidation by the action of mitoxantrone.
AB  - Mitoxantrone was used as an immunosuppressive probe to elucidate a means for the
      control of experimental allergic encephalomyelitis (EAE) induced in Biozzi AB/H
      mice following injection of spinal cord homogenate emulsified in Freund's
      adjuvant. A single i.p. injection of 2.5 mg/kg of mitoxantrone, 1-2 days before
      the anticipated onset of EAE, failed to prevent the majority of animals from
      developing clinical disease, whereas when the compound was injected directly into
      the central nervous system (CNS), at this time point, significantly increased
      therapeutic benefit was evident, with most animals failing to develop clinical
      EAE. Although the clinical use of intrathecal mitoxantrone is strongly
      contraindicated, these data suggest that increased therapeutic benefit may be
      achieved in immune-mediated disease of the CNS by targeting immunosuppressive
      doses of suitable agents, on lymphocyte activation within the CNS. In addition,
      direct administration of immunosuppressive doses into the CNS may reduce
      potentially unwanted (side) effects in the periphery.

PMID- 1395093
TI  - Mesangial sclerotic change with persistent proteinuria in rats after two
      consecutive injections of monoclonal antibody 1-22-3.
AB  - Irreversible mesangial changes with persistent proteinuria were induced in rats
      given two consecutive injections 2 weeks apart of a MoAb 1-22-3 to rat mesangial
      cell. The characteristics of the resulting lesions were investigated and compared
      with those of the reversible change induced by a single injection. At 24 h after
      the second injection, mesangiolytic changes similar to those after a single
      injection were evident. The accumulation of macrophage-like cells in glomeruli
      observed at 1 week after the first injection was not evident during the
      experimental period after the second injection. Hypercellularity with the
      characteristics of intrinsic mesangial cell and increased mesangial matrix were
      already present 1 week after the second injection. And mesangial sclerotic change
      progressed up to 6 months. Deposition of collagen type I and type III and
      accumulation of collagen fibril at the ultrastructural level were evident in rats
      6 months after the second injection. Proteinuria started immediately and
      continued for more than 6 months after the second injection. The mesangial
      sclerotic change with persistent proteinuria described here is considered to be a
      better model for investigating the mechanism of chronic progression of human
      mesangial proliferative glomerulonephritis.

PMID- 1395094
TI  - Human immunoglobulin production in immunodeficient mice: enhancement by
      immunosuppression of host and in vitro activation of human mononuclear cells.
AB  - The affect of host and donor related factors on successful engraftment of human
      cells into mice was examined to minimize the variability that has been observed
      in successful development of human-mouse chimera for the study of human disease
      and immune physiology and regulation. Human immunoglobulin production in severe
      combined immunodeficiency (SCID) mice engrafted with human peripheral blood
      mononuclear cells (PBMC) was augmented by immunosuppressing recipient mice and
      activating donor PBMC. Immunosuppression of recipient mice with 3 Gy of gamma
      irradiation induced a 10-fold increase in human IgG in the sera of engrafted SCID
      mice. Variation in production of human IgG in recipient mice correlated with
      preinjection phenotype and activation status of injected PBMC. Mice injected with
      PBMC with a low CD4/CD8 ratio (less than 0.5) produced no detectable circulating
      human immunoglobulin. When the CD4/CD8 ratio was greater than 1.5, human IgG was
      detected in sera of PBMC-recipient SCID mice. Serum IgG increased 10-fold
      following in vitro activation of donor PBMC with anti-CD3, IL-2 and
      Staphylococcus aureus. Successful engraftment and serum IgG production was
      evidenced by an increase in the recovery of activated human IgG+ cells in the
      spleens of mice with maximal IgG production. Optimization of functional
      engraftment required modification of both the host (SCID mice) and the donor
      cells.

PMID- 1395095
TI  - Structure and expression of the mb-1 transcript in human lymphoid cells.
AB  - The mb-1 gene encodes a protein associated with membrane-bound immunoglobulins
      (mIg) and it has been suggested that it may play a role in signal transduction.
      Using a murine probe, we cloned a human complementary DNA homologous to the
      murine mb-1 sequence. Its complete sequence is in full agreement with a recently
      published human cDNA sequence but differs from a previously reported partial
      sequence. We studied mb-1 expression in human cells at various maturation stages.
      Large amounts of a single 1.4 kb transcript were detectable in B cell lines
      carrying mIg of the mu, gamma, alpha 1 or alpha 2 isotype. The mb-1 mRNA was also
      expressed in pre-B cells and in cells expressing truncated membrane mu chains
      devoid of associated light chains. Only trace amounts of mb-1 mRNA were found in
      tissue samples containing numerous plasma cells, while no mRNA was detected in
      several plasmacytoma cell lines, indicating that expression is shut down in
      plasma cells. No signal was found in T cells or in non-lymphoid tissues.
      Altogether, these results show that the human mb-1 gene is expressed in pre-B
      cells and B lymphocytes, regardless of the isotype of the mIg heavy chain and is
      no longer expressed in plasma cells.

PMID- 1395096
TI  - Endoglin: a 180-kD endothelial cell and macrophage restricted differentiation
      molecule.
AB  - A MoAb RMAC8 was generated by immunizing Balb/c mice with cultured human
      umbilical vein endothelial cells (HUVE). The molecule recognized had a mol. wt of
      180 kD non-reduced, 95 kD after reduction and 66 kD in its reduced and N
      deglycosylated form. Sequential immunoprecipitation studies with the MoAb 44G4,
      which recognizes the O- and N-glycosylated homodimer endoglin, showed that both
      MoAbs recognize the same molecule on HUVE and phorbol myristate acetate (PMA)
      stimulated U937 cells. The distribution of the RMAC8-recognized molecule was the
      same as that described for endoglin, i.e. arterial and venous endothelium,
      myelomonocytic and pre-B leukaemia cells and cell lines; however, unlike 44G4,
      RMAC8 also reacted weakly with monocytes and strongly with in vitro
      differentiated macrophages as well as peritoneal and alveolar macrophages. This
      distribution of endoglin was confirmed by Northern blot analysis using a full
      length endoglin cDNA probe. These studies suggest that endoglin is a
      differentiation marker on macrophages.

PMID- 1395097
TI  - Immunophenotypical alterations in a subset of patients with common variable
      immunodeficiency (CVID).
AB  - We investigated the expression of surface molecules on lymphocytes from 20
      patients with CVID and 40 healthy subjects. Lymphocytes were analysed by dual
      colour flow cytometry. We identified a subset of patients (8 of 20) characterized
      by low CD4/CD8 ratio (less than 1.1), expansion of T cells co-expressing the
      activation marker HLA-DR and significant increase in CD8+ T cells co-expressing
      CD57. Expression of the adhesion molecules LFA-3 (CD58) and ICAM-1 (CD54) was
      significantly increased in this subgroup. In addition, within the CD4+ T cells
      the percentage of CD29+ (memory) cells was increased, while the CD45RA and LAM-1
      (Leu-8) antigens were depressed. These results indicate that in a subgroup of
      CVID patients T cells are activated in vivo and the CD57+CD8+ lymphocyte
      subpopulation, supposed to comprise functional suppressor T cells, is expanded.
      We suggest a chronic viral infection in these patients, but it is not clear
      whether this is primary or secondary to the underlying defect.

PMID- 1395098
TI  - The concentration of the C-type lectin, mannan-binding protein, in human plasma
      increases during an acute phase response.
AB  - Two ELISAs for estimating mannan-binding protein (MBP) were constructed and the
      concentration of MBP in plasma was followed in patients undergoing major surgery
      and in patients having a malarial attack. In both cases increases of MBP in the
      plasma were observed. The relative increase and the kinetics varied from person
      to person. The concentration of MBP increased between 1.5- and three-fold
      following surgery. In some patients an increase was seen at day 1 whereas in
      others the increase was not observed until days 3-9. In the malaria patients an
      increased level of MBP was maintained during 30 days of treatment with
      chloroquine. The relative increase in MBP was independent of the presurgery or
      premalaria levels.

PMID- 1395099
TI  - Evaluation of serum levels of tumour necrosis factor-alpha (TNF-alpha) and
      soluble IL-2 receptor (sIL-2R) and CD4, CD8 and natural killer (NK) populations
      during infrared pulsed laser device (IPLD) treatment.
AB  - The purpose of this study was to evaluate serum levels of TNF-alpha, sIL-2R and
      distribution of peripheral leucocyte subsets in patients with advanced neoplastic
      disease undergoing IPLD treatment. Fifteen cancer patients with evidence of
      persistent disease were further divided in two groups according to outcome at the
      end of the period of clinical evaluation: group 1 patients were still alive and
      group 2 patients had died. Our results show: (i) an increase in the initial level
      of TNF-alpha in both groups; (ii) a decrease in TNF-alpha levels during the
      follow up of group 1 patients; (iii) a significant increase in serum levels of
      sIL-2R in patients in group 2 compared with those in group 1; (iv) a progressive
      and constant increase in TNF-alpha levels in group 2; (v) a decrease in
      CD4+CD45RA+ subpopulation in both groups; (vi) an increase in CD25+ cells; (vii)
      an increase in CD4+, CD4+CD45RA+ and CD25+ cells during the follow up of group 2
      patients. The data generated here form the basis for further investigations on
      the use of IPLD as a single agent and in combination with other biological
      response modifiers in cancer patients.

PMID- 1395100
TI  - Alterations in mononuclear cell tumour necrosis factor-alpha (TNF-alpha) response
      in patients on long term cuprophane haemodialysis.
AB  - We have investigated TNF-alpha secretory response of peripheral blood mononuclear
      cells (PBMC) from 13 uraemic patients undergoing regular haemodialysis with
      cuprophane membrane (CM). Sixteen healthy subjects and five uraemic patients
      under conservative therapy were also studied as controls. Cells of haemodialysis
      patients exhibited increased TNF-alpha release in vitro in the absence of
      activating stimuli other than culture conditions, as compared with normal and
      uraemic controls. In contrast to normal cells, this spontaneous secretion of TNF
      alpha from dialysis PBMC could not be significantly reduced by addition of
      polymyxin B to culture medium, thus indicating its independence of trace amount
      of lipopolysaccharide (LPS) present in the medium as contaminant. Furthermore,
      predialysis PBMC were considerably more sensitive to stimulation with 10(7) pg/ml
      of LPS under in vitro culture conditions than normal and uraemic controls. To
      elucidate a role of direct contact with CM in stimulation of TNF-alpha release
      from monocytes, PBMC were cultured on CM in vitro. Contact with CM stimulated TNF
      alpha secretion from PBMC above the level of cells cultured on tissue culture
      plastic. This response persisted with time in culture in contrast to a transient
      LPS-induced TNF-alpha release. Furthermore, PBMC stimulated by contact with CM
      for 2 days did not lose the capacity to secrete TNF-alpha in response to a
      subsequent LPS stimulation, while a 2-day treatment of cells with LPS was
      followed by LPS refractory state. Therefore, direct contact with CM induces in
      PBMC a long-lasting TNF-alpha response which is not down-regulated by the
      acquisition of refractoriness in a manner similar to that which occurs in the
      case of LPS stimulation. These in vitro findings provide a possible explanation
      of the observation that predialysis PBMC exhibit elevated TNF-alpha secretory
      capacity.

PMID- 1395101
TI  - Haemodialysis as a model for studying endogenous plasma DNA: oligonucleosome-like
      structure and clearance.
AB  - The rate of clearance of extracellular plasma DNA in man has important
      implications for pathogenetic mechanisms in systemic lupus erythematosus (SLE),
      as well as for certain other clinical states. Present knowledge of this parameter
      is derived exclusively from studies of injected, naked DNA in animals. Recent
      information indicates that the physiologic form of plasma DNA in SLE is that of
      oligonucleosome-like molecules rather than of naked DNA and consists of
      multimeric complexes of DNA bound to histone, probably arising from an apoptotic
      process. In order to study the rate at which these oligonucleosome-like complexes
      are removed from plasma and to do so in man rather than experimental animals, we
      exploited the observation that during haemodialysis large amounts of DNA are
      released, apparently within the dialysis coil, into the patient's plasma. Since
      this release appears to cease promptly with termination of the procedure, it
      offered the potential for estimating the rate of removal of such DNA from human
      plasma. Moreover, if that DNA, as postulated, were shown to possess an
      oligonucleosome-like structure resembling that found endogenously in human SLE,
      the relevance of such information to the human disease state would be further
      enhanced. The present results support the conclusion that DNA released into
      plasma during haemodialysis possesses such an oligonucleosome-like structure. The
      plasma half-life of that DNA in man was found not to exceed 4 min. The highly
      dynamic state thus implied for extracellular endogenous plasma DNA in man has
      important implications for pathogenetic mechanisms dependent on dsDNA in SLE.
      Moreover, individuals undergoing chronic haemodialysis, who are thereby exposed
      to a very large cumulative amount of such DNA, might serve as models for studying
      its long-term sequelae.

PMID- 1395102
TI  - Heterogeneous effects of exogenous IL-2 on HIV-specific cell-mediated immunity
      (CMI).
AB  - A characteristic feature associated with HIV-1 infection of the human host is a
      chronic decline in circulating CD4+ T helper/inducer cell numbers. Impaired cell
      mediated immune functions usually occur in parallel with the decline in CD4+ T
      cells. Activated CD4+ T helper cells are a major source of endogenous IL-2 which
      is required for the immunoregulation of both antigen-specific B cells and CD8+ T
      cells. HIV-specific T cell proliferative responses are said to be weak and
      inconsistent, even during the asymptomatic phase of disease. We thus wished to
      determine how exogenous IL-2 affected HIV-specific T cell proliferation at
      different stages of the disease. Our cohort of 81 included both asymptomatic and
      symptomatic HIV-infected patients as well as uninfected normal donors.
      Proliferative responses of peripheral blood mononuclear cells (PBMC) that were
      elicited during culture with an immunodominant gp41-derived synthetic peptide,
      gp41[8], and which were known to be CD8+ cell-associated in asymptomatics only,
      were used to analyse the effects of exogenous IL-2. IL-2 had three main effects
      on HIV-specific proliferation, namely (i) an additive effect, (ii) a synergistic
      effect, and (iii) an induced effect. More specifically, low dose exogenous IL-2
      frequently augmented lymphoproliferation in both asymptomatic and symptomatic
      gp41[8] responders. In most symptomatics, however, who were predominantly gp41[8]
      non-responders, exogenous IL-2 induced lymphoproliferation. Flow cytometric
      analyses using dual immunofluorescence were used to analyse the T cell subset
      distribution of proliferating PBMC cultures. During culture with gp41[8], both
      CD4+ and CD8+ T cell numbers increased. However, after the addition of exogenous
      IL-2 to gp41[8]-containing cultures, CD8+ cell-associated lymphoproliferative
      responses were preferentially augmented. These results suggest that in
      symptomatics there is an inadequate supply of endogenous IL-2 to help maintain
      the strong and effective CD8+ cell-associated anti-viral immunity, and an
      exogenous supply of IL-2 may be required.

PMID- 1395103
TI  - Tumour necrosis factor enhances the asbestos-induced production of reactive
      oxygen metabolites by human polymorphonuclear leucocytes (PMN).
AB  - We studied the effect of recombinant tumour necrosis factor-alpha (TNF-alpha) on
      the production of reactive oxygen metabolites (ROM) by human PMN exposed in vitro
      to chrysotile and crocidolite asbestos fibres, quartz dusts and opsonized
      zymosan. TNF caused a significant increase in ROM release by PMN, and
      significantly and dose-dependently amplified the ROM production induced by
      asbestos fibres. The amplification of ROM production by TNF can be of crucial
      importance in the process of lung inflammation and fibrogenesis in
      pneumoconioses.

PMID- 1395104
TI  - Endothelial cell damage in primary biliary cirrhosis: influence of cholestasis
      and immunological mechanisms.
AB  - In a study looking for evidence of endothelial cell damage in primary biliary
      cirrhosis, serum from patients was found to be significantly more cytotoxic to
      cultured endothelial cells in vitro than normal control serum (P less than
      0.001). Serum also contained higher levels of von Willebrand factor antigen
      (vWFAg, a specific product of the endothelium) than control serum (P less than
      0.001). Cytotoxicity correlated with serum levels of vWFAg (P less than 0.05) and
      with serum bilirubin (P less than 0.05). No correlations were found between
      cytotoxicity and circulating immune complexes, C-reactive protein or CH50. The
      study was controlled by serum from patients with other liver diseases. In these
      samples vWFAg (P less than 0.003), and bilirubin levels (P less than 0.001) were
      also raised relative to normal controls. vWFAg levels again correlated with
      levels of bilirubin (P less than 0.05). Tissue culture experiments showed that
      purified bilirubin was cytotoxic to human umbilical vein endothelial cells and
      induced the release of vWFAg. The case report of a patient with obstructive
      jaundice again indicated that levels of bilirubin and vWFAg were related. These
      results suggest that endothelial cell damage occurs in both primary biliary
      cirrhosis and to a lesser extent in other liver diseases, and may be mediated by
      cholestasis, not by humoral immunological mechanisms.

PMID- 1395106
TI  - Responsiveness and sensitivity to cholinergic agonists and antagonists in bovine
      isolated bronchial muscle.
AB  - 1. Airways derived from different levels of the lung exhibit a difference in the
      reactivity and sensitivity to agonists. We have evaluated the effect of
      acetylcholine and cholinergic selective (pirenzepine, gallamine and 4
      dipherylacetoxymethyl piperidine [4-DAMP]) and non-selective (atropine)
      antagonists on bovine proximal and distal smooth muscle preparations. 2. The
      distal preparations are more sensitive to acetylcholine than proximal bronchi.
      The relaxant effect of three selective antagonists on the distal and proximal
      tissues was the same when the results for each drug were compared. 3. Atropine
      and 4-DAMP were more potent than pirenzepine and gallamine in relaxing both
      proximal and distal bovine smooth muscle preparations. 4. These data suggest that
      the muscarinic sites on the smooth muscle of bovine airways are of the M3
      subtype.

PMID- 1395105
TI  - Atrial natriuretic peptide in pregnancy: response to oral sodium supplementation.
AB  - 1. The control of extracellular fluid volume (ECFV) in normal pregnancy may be
      related to changes in atrial natriuretic peptide. Previous studies in non
      pregnant subjects have suggested that plasma atrial natriuretic peptide (ANP)
      increases in response to dietary sodium supplementation because of an increase in
      plasma volume, although this has not been measured directly. 2. Nine women who
      were pregnant in the third trimester undertook oral sodium supplementation (136
      mmol) for 5 days in addition to their usual diet. Twenty-four hour urinary sodium
      excretion increased by 125 +/- 54 mmol/day (mean +/- s.d.; P less than 0.01).
      Plasma volume was unchanged, although total ECFV tended to increase (P less than
      0.09 and bodyweight increased (1.3 +/- 1.4 kg; P less than 0.01) at the end of
      these diets. 3. Plasma ANP increased by 30.7 [8.6, 34.5] pmol/L (median [25th,
      75th percentile]; P less than 0.05), while plasma renin concentration decreased
      significantly from 7.3 [6.2, 11.2] to 2.6 [1.7, 3.9] pmol angiotensin I/mL (P
      less than 0.01), as did plasma aldosterone concentration (1435 [1162, 1722] to
      753 [595, 1110] fmol/mL; P less than 0.01). Plasma vasoactive intestinal peptide
      was unchanged. 4. Pregnant women respond to increased dietary sodium with an
      increase in plasma ANP in the absence of a significant increase in plasma volume.
      The acute regulation of plasma ANP in response to increases in dietary sodium in
      pregnant women does not appear to be mediated by changes in intravascular fluid
      volume.

PMID- 1395107
TI  - Prejunctional actions of tacrine on autonomic neuroeffector transmission in
      rabbit isolated pulmonary artery and rat isolated atria.
AB  - 1. This study investigated the effects of tacrine (1,2,3,4-tetrahydro-9
      aminoacridine) on the resting and stimulation-induced (SI) release of radioactive
      substances from isolated preparations of rat atria and rabbit pulmonary artery in
      which the noradrenergic transmitter stores had been labelled with [3H]
      noradrenaline, and from rat atrial preparations in which cholinergic transmitter
      stores had been labelled with [3H]-acetylcholine. In addition, the effect of
      tacrine on the uptake of [3H]-noradrenaline by noradrenergic nerves in rat atria
      was determined. 2. Tacrine produced concentration-dependent increases in the
      resting efflux of radioactivity from both the [3H]-noradrenaline-loaded artery
      and atrial preparations. Blockade of neuronal amine transport with desipramine
      reduced the release of radioactivity evoked by tacrine from atria but not that
      evoked from artery preparations. Inhibition of monoamine oxidase by pargyline
      pretreatment markedly reduced the tacrine-evoked release of radioactivity in both
      atrial and artery preparations. 3. The radioactivity released from [3H]
      noradrenaline-labelled rat atrial preparations by 30 mumol/L tacrine consisted
      entirely of the deaminated metabolite [3H]-DOPEG. The evoked release of [3H]
      DOPEG from atria was reduced by approximately 50% by desipramine (1 mumol/L).
      When atrial monoamine oxidase had been inhibited by pargyline treatment in vivo
      and in vitro, 30 mumol/L tacrine evoked the release of [3H]-noradrenaline instead
      of [3H]-DOPEG. However, the amounts of [3H]-noradrenaline released by tacrine
      when monoamine oxidase was inhibited were only about 25% of the amounts of [3H]
      DOPEG released in untreated atria. 4. Tacrine, in concentrations of 1 and 10
      mumol/L, enhanced the release of radioactivity evoked by field stimulation of
      [3H]-noradrenaline-loaded rabbit pulmonary artery preparations. This effect was
      unaltered by desipramine or pretreatment with pargyline. However, in artery
      preparations pretreated with pargyline, a high concentration of tacrine (100
      mumol/L) markedly reduced SI efflux. In contrast to the findings with artery
      preparations, tacrine (1-30 mumol/L) did not alter SI efflux in rat atrial
      preparations. 5. It is concluded that tacrine displaces noradrenaline from
      intraneuronal transmitter stores of sympathetically-innervated tissues, and that
      the displaced amine is totally metabolized by monoamine oxidase before leaving
      the nerve terminals. When deamination of neuronal cytoplasmic noradrenaline is
      prevented, only a portion of the noradrenaline displaced from storage vesicles
      passes to the extracellular space. It is likely that the transfer of cytoplasmic
      noradrenaline out of the terminals is limited by the activity of the amine
      transport mechanism.

PMID- 1395108
TI  - Intracoronary PGE2 and veratrine inhibits renin release in conscious dogs via
      chemosensitive ventricular afferents.
AB  - 1. Prostaglandins (PG) and veratrum alkaloids stimulate ventricular sensory
      receptors with non-myelinated vagal afferents and mediate inhibitory circulatory
      responses. 2. The present study in conscious instrumented dogs was carried out to
      determine the effects of intracoronary artery infusions of veratrine (Ver-IC) and
      PGE2 (PGE2-IC) on plasma renin activity (PRA). 3. A 15-20 mmHg decrease in
      arterial pressure was produced during Ver-IC (0.2-0.8 micrograms/kg per min) and
      PGE2-IC (10-50 ng/kg per min), but there was no change in PRA or heart rate. 4.
      In contrast, significant increases in PRA (+3.51 +/- 0.37 ng angiotensin I/mL per
      h; P less than 0.01) and heart rate (+38.5 +/- 6.2 beats/min; P less than 0.001)
      were elicited in response to a 15-20 mmHg decrease in arterial pressure produced
      by intravenous infusions of nitroprusside. 5. Pharmacological blockade of
      afferent fibres in the pericoronary region of the left main coronary artery
      during Ver-IC resulted in significant hypotension-induced increases in PRA (P
      less than 0.001) and heart rate (P less than 0.001), thus removing the inhibitory
      influence of chemosensitive ventricular afferents. 6. Therefore, intracoronary
      veratrum alkaloids and prostaglandins inhibit hypotension-induced increases in
      PRA and heart rate in the conscious dog. This is mediated by chemosensitive
      receptors located in the left ventricular myocardium along with afferent nerves
      in the pericoronary region and cervical vagi.

PMID- 1395109
TI  - Does the haemodynamic response to acute central hypovolaemia depend on the rate
      of fall of cardiac output?
AB  - 1. In published studies of the effects of acute blood loss in conscious rabbits,
      the rates of haemorrhage have ranged for 3-9% of blood volume/min. This is
      potentially a confounding factor when it comes to comparing the results of
      different studies. We have therefore tested whether the haemodynamic response to
      acute central hypovolaemia depends on the rate of fall of cardiac output. 2.
      Cardiac output in six conscious rabbits was reduced by 4, 8 and 12% of baseline
      levels per min by gradual inflation of a cuff around the thoracic inferior vena
      cava. These rates correspond approximately to blood loss at rates of 3, 6 and 9%
      of blood volume/min. 3. The haemodynamic responses were biphasic. In Phase I
      (compensatory) there was progressive systemic vasoconstriction and tachycardia,
      and only a small fall in blood pressure. In Phase II (decompensatory), systemic
      vasoconstriction failed abruptly, arterial pressure plummeted and heart rate
      declined. 4. We could detect no effect of rate of fall of cardiac output on the
      pattern of the haemodynamic responses in either Phase I or Phase II. 5. We
      conclude that the rate of blood loss in different studies of haemorrhage in
      conscious rabbits, within the range 3 to 9 per cent of blood volume per minute,
      need not be regarded as a confounding factor when it comes to interpreting the
      results. It is likely that this conclusion can be generalized to studies of
      haemorrhage in other mammalian species.

PMID- 1395110
TI  - Enhancement by endothelin-1 of the release of catecholamines from the canine
      adrenal gland in response to splanchnic nerve stimulation.
AB  - 1. The effect of endothelin-1 on the release of adrenal catecholamines was
      examined in anaesthetized dogs. 2. Splanchnic nerve stimulation (SNS) at 1 and 3
      Hz was applied before and after the intravenous injection of endothelin-1. 3.
      Endothelin-1 (0.1 and 0.3 micrograms/kg) significantly enhanced the release of
      adrenal catecholamines induced by 3 Hz SNS, but did not affect basal release and
      the release of adrenal catecholamines induced by 1 Hz SNS. 4. Endothelin-1
      produced a slight and short-lasting fall in arterial blood pressure and decreases
      in adrenal and renal blood flow rates. 5. These results indicate that endothelin
      1 enhances the release of adrenal catecholamines from the canine adrenal gland in
      response to relatively high frequency SNS.

PMID- 1395111
TI  - Effect of perindopril on the development of atherosclerosis in the cholesterol
      fed rabbit.
AB  - 1. The aim of the study was to examine the effect of the angiotensin-converting
      enzyme inhibitor perindopril on the development of atheroma in the cholesterol
      fed rabbit. 2. The normal human carotid artery, like most large human arteries,
      has a preformed diffuse intimal thickening. To model this thickening, the right
      carotid artery of the 12-week-old rabbit had an expanded balloon catheter passed
      down it to remove the endothelium and partially damage the media. 3. Fourteen
      weeks after this operation, a myointimal thickening similar in almost all
      respects to the human intimal thickening had developed. The rabbits were then
      divided into six groups of six rabbits fed on: (i) a 1% cholesterol diet; (ii) a
      1% cholesterol diet plus a hypotensive dose of perindopril (0.3 mg/kg per day);
      (iii) a 1% cholesterol diet plus a non-hypotensive dose of perindopril (0.01
      mg/kg per day); (iv) a normal diet; (v) a normal diet plus a hypotensive dose of
      perindopril (0.3 mg/kg per day); and (vi) a normal diet plus a non-hypotensive
      dose of perindopril (0.01 mg/kg per day). 4. After 6 weeks of treatment the
      animals were sacrificed. There were ameliorating effects of both hypotensive and
      non-hypotensive doses of perindopril on the development of plaques, as determined
      by the area of intima covered by Oil Red-O-staining plaque and light microscopy.
      5. Cell culture studies indicated that perindopril has no effect on smooth muscle
      proliferation, but increases collagen and non-collagen synthesis by smooth muscle
      cells and decreases their binding of the atherogenic lipoprotein beta-very low
      density lipoprotein (beta-VLDL).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395112
TI  - A developmental genetic mechanism involving angiotensin in spontaneously
      hypertensive rats.
AB  - 1. Certain genes drive the blood pressure of young spontaneously hypertensive
      rats (SHR) to stable hypertensive levels in adulthood. 2. Relatively brief
      blockade of the renin-angiotensin system in young SHR can reset the track of SHR
      pressure to a lower level for the life of the animal. This effect appears to be a
      characteristic of the SHR strain. 3. It is proposed that the expression of a
      particular SHR hypertensive gene depends on angiotensin and is limited to young
      animals. This hypothesis explains some of the phenotypic abnormalities observed
      in young SHR and the decremental long-term blood pressure effects following ACE
      inhibitor treatment. 4. The identity of the gene is unclear, but information from
      biochemical, physiological and pharmacological studies may direct attention to
      distinct candidate genes within specific chromosomal regions of interest. 5.
      Understanding these genetic mechanisms may have important implications for future
      preventive strategies.

PMID- 1395114
TI  - The effect of hypertension and ACE inhibition on arterial structure and
      compliance.
AB  - 1. Large artery dilatation may be produced by angiotensin-converting enzyme
      inhibition in hypertensive subjects independently of blood pressure reduction.
      The resulting increase in arterial compliance may be due to both blood pressure
      reduction and to arterial smooth muscle relaxation. 2. In healthy volunteers and
      in hypertensive subjects, dosages producing large artery dilatation seem to be
      even higher than those causing arteriole dilatation with the resulting blood
      pressure reduction. 3. It may be important to consider such findings for the
      remodelling of the cardiovascular system produced by angiotensin-converting
      enzyme inhibition.

PMID- 1395113
TI  - Diabetic renal microvascular disease: the role of hypertension and ACE
      inhibitors.
AB  - 1. It has been suggested that hypertension may be an important determinant of the
      rate of progression of diabetic microangiopathy. 2. Renal microvascular disease
      as assessed by urinary albumin excretion and glomerular ultrastructure was
      evaluated in a model in which streptozotocin diabetes was induced in
      spontaneously hypertensive rats (SHR). 3. Diabetes was associated with increases
      in urinary albumin excretion, and hypertension resulted in a further increase in
      albuminuria. 4. Various antihypertensive regimens were administered to diabetic
      SHR, with the angiotensin-converting enzyme inhibitor perindopril and triple
      therapy (hydralazine, reserpine and hydrochlorothiazide) being more effective
      than the calcium antagonist (lacidipine) in retarding the increase in albuminuria
      in diabetic SHR. 5. Antihypertensive therapy appears to ameliorate the
      development of diabetic renal disease.

PMID- 1395115
TI  - Remodelling of the vascular system in response to hypertension and drug therapy.
AB  - 1. Arterial remodelling is an important mechanism in the pathophysiology of
      hypertension and its complications, being involved in the decrease of vascular
      reserve, the autoregulation of cerebral blood flow and the development of
      atherosclerosis. There is now evidence that, in addition to several other growth
      factors, vasoactive peptides such as angiotensin II may act as vascular smooth
      muscle growth-promoting substances. Based on these data, the effects of
      perindopril, a potent and long-lasting angiotensin-converting enzyme (ACE)
      inhibitor, on structural and mechanical properties of the arterial wall have been
      studied in animal models of hypertension. Perindopril completely reversed the
      aortic medial hypertrophy and arterial stiffening observed in renovascular
      hypertensive rats and in spontaneously hypertensive rats. The effect of
      perindopril was consistent with the potent inhibition of vascular ACE, and
      emphasized the potential role of angiotensin II as a vascular growth modulator.
      Whether the time constant of remodelling is similar or not in the heart and large
      vessels remains an important question that requires further investigation.

PMID- 1395116
TI  - Enhanced contraction to noradrenaline, serotonin and nerve stimulation but normal
      endothelium-derived relaxing factor response in skin small arteries in human
      primary hypertension.
AB  - 1. We measured the reactivity of 2 mm long ring segments of human resistance
      arteries dissected from gluteal skin biopsies and mounted on wires in a Mulvany
      Halpern myograph for recording isometric force. Arteries were taken from eight
      normotensive (N) volunteers (average age 46 years, blood pressure 126/82 mmHg)
      and eight untreated hypertensives (H; average age 48 years, blood pressure
      149/101 mmHg). 2. In small diameter arteries (internal diameter less than 500
      microns), the cumulative concentration-response curves to noradrenaline,
      serotonin and angiotensin II had a greater maximum by 72, 300 and 69%,
      respectively, in vessels from hypertensive patients than in those from normal
      volunteers. Nerve stimulation also caused a greater maximum contraction in
      hypertensive vessels (by 352%). 3. Arteries from H and N patients contracted
      submaximally by the thromboxane mimetic U46619 were similarly sensitive to the
      endothelium-dependent relaxing factor (EDRF) acetylcholine, indicating no
      difference in EDRF release or sensitivity. 4. Morphological measurements of the
      ratio of wall thickness to lumen radius of the wire-mounted vessels showed no
      significant difference between H and N vessels. 5. In larger arteries (internal
      diameter greater than 500 microns), no response to acetylcholine was noted in
      either H or N arteries. The sensitivity to serotonin and angiotensin II was
      similar between these arteries but the EC50 to noradrenaline was less in H than
      in N arteries (delta EC50 = 0.61 -log mol/L). 6. Subcutaneous resistance arteries
      with an internal diameter less than 500 microns from hypertensive patients show
      enhanced contractility to noradrenaline, serotonin and nerve stimulation despite
      a lack of detectable medial hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395117
TI  - The clinical pharmacology of ACE inhibitors: evidence for clinically relevant
      differences?
AB  - 1. Potential differences among ACE inhibitors include pharmacokinetic and
      pharmacodynamic factors. The presence of a sulfhydryl group conferring
      antioxidant properties, the administration as a pro-drug to delay the onset and
      prolong the duration of haemodynamic effects, and the route of elimination are
      examples of possible differences. 2. Adverse effects of ACE inhibitors may be
      mediated by effects on bradykinin metabolism at tissue sites, which may be
      separable from haemodynamic responses mediated largely by angiotensin II
      withdrawal. 3. Clinically important differences between ACE inhibitors in their
      adverse event profile have yet to be proven. Evidence is emerging that plasma ACE
      inhibition and haemodynamic responses are separable, and this may indicate the
      potential for other organ-specific effects to differ among ACE inhibitors. 4. At
      present, however, the greatest distinguishing features for one compound vs
      another are the time to onset and the duration of action, which determine the
      frequency of administration.

PMID- 1395118
TI  - Clinical efficacy of perindopril in hypertension.
AB  - 1. Perindopril's effectiveness in mild to moderate hypertension was evaluated in
      three studies. 2. Perindopril was more effective than sodium restriction in
      reducing blood pressure, and the effects were additive. 3. Perindopril was as
      effective as atenolol in reducing blood pressure, and was well tolerated. 4.
      Perindopril lowered blood pressure to the same extent as enalapril at peak drug
      levels but had a greater effect at the trough level of the drugs. 5. Perindopril
      is an effective antihypertensive agent with an acceptable side-effect profile in
      people with hypertension.

PMID- 1395119
TI  - Angiotensin-converting enzyme inhibition as first-line treatment for
      hypertension.
AB  - 1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b.d.)
      or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies
      involving a total of 503 hypertensive patients with a diastolic blood pressure
      (DBP) of 95-125 mmHg. 2. A 4 week single-blind placebo period preceded 12 weeks
      of active treatment. Dose titration was at weeks 4 and 8 if supine DBP greater
      than 90 mmHg. The dose was doubled and if necessary a diuretic was added in the
      atenolol or captopril comparisons, and atenolol was added in the diuretic study.
      3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and
      21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril
      and 48% on atenolol, increasing to 78% and 58% with the addition of
      hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg
      compared with 27/18 mmHg for perindopril, with 49% of both groups being
      controlled on monotherapy. 4. Diuretic addition produced a greater
      antihypertensive effect with perindopril (75%) compared with 57% for captopril in
      achieving control. Perindopril caused a comparable fall in supine BP to the
      diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP
      was significantly greater for the diuretic. At 3 months, 85% of the diuretic
      group and 78% of the perindopril group achieved the target BP. 5. A multicentre
      trial of 856 patients treated with perindopril (690 patients treated for 1 year
      or more) has shown that BP control is maintained in the long term with a low
      incidence of side-effects (7.9%) causing withdrawal from treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1395120
TI  - Transforming growth factor-beta in the regulation of the immune response.

PMID- 1395121
TI  - Expression of interleukin-1 and interleukin-1 receptor antagonist by human
      rheumatoid synovial tissue macrophages.
AB  - Interleukin-1 (IL-1) has protean effects in the pathogenesis of rheumatoid
      arthritis (RA). These effects include production of prostaglandins and
      collagenase from rheumatoid fibroblasts as well as upregulation of adhesion
      molecule expression on these cells. IL-1 can activate monocytes and neutrophils,
      as well as promote the growth of fibroblasts and endothelial cells. Recently, a
      novel interleukin-1 receptor antagonist protein (IRAP) has been isolated,
      purified, cloned, and expressed, which may modulate the effects of IL-1. In this
      study, we present data demonstrating that macrophages isolated from human RA
      synovial tissues express both IL-1 and IRAP genes. In addition, RA synovial
      tissue macrophages and lining cells display IL-1 and IRAP antigenic expression by
      immunohistochemistry. In contrast, osteoarthritis synovial tissues, as compared
      to RA, have fewer IL-1 and IRAP-positive macrophages. Thus, the production of IL
      1 balanced by IRAP may affect the joint destruction found in these diseases.

PMID- 1395122
TI  - Stimulation of human peripheral blood mononuclear cells with anti-CD3 monoclonal
      antibody vs IL2: disparate effects on T cell-dependent B cell differentiation
      despite similar effects on generation of unrestricted cytolytic activity.
AB  - Despite their each inducing MHC-unrestricted cytolytic activity in overnight PBMC
      cultures mediated predominantly by CD56+ non-T cells, anti-CD3 mAb and rIL2
      induce diametrically opposite effects on subsequent polyclonal T cell-dependent B
      cell differentiation. When added to fresh autologous PBMC, irradiated anti-CD3
      stimulated PBMC inhibit generation of Ig-secreting cells (IgSC) in the secondary
      cultures, whereas irradiated rIL2-stimulated PBMC enhance IgSC generation.
      Neither carryover of the respective stimuli nor quantitative differences in
      levels of cytolytic activity against Daudi cells, autologous PBMC, or autologous
      activated B cells can explain the dichotomous anti-CD3- vs rIL2-induced effects
      on B cell differentiation. For both anti-CD3- and rIL2-induced effects on B cell
      differentiation, CD56- cells, including CD4+ and CD8+ cells, play a more dominant
      role than they do in generation of MHC-unrestricted cytolytic activity. In
      addition, although rIL2-induced enhancement of IgSC generation is insensitive to
      monocyte depletion by plastic adherence or by treatment with leucine methyl
      ester, anti-CD3-induced inhibition of IgSC generation is highly sensitive to
      monocyte depletion, indicating that, at least for anti-CD3-induced inhibition,
      multiple cell populations are required to generate the functional effect. Taken
      together, these results indicate that differences in the means of generating in
      vitro tumoricidal activity may have profound ramifications for non-cytotoxic
      immune parameters, such as B cell differentiation. Not only might this be an
      important issue to address in adoptive immunotherapy protocols for cancer
      patients but also adoptive immunotherapy might be applicable to certain
      autoimmune disorders if the ability to inhibit B cell differentiation could be
      channeled against the pathogenic antibody-producing B cells.

PMID- 1395123
TI  - Modification of thymic cell subsets induced by long-term cocaine administration
      during a murine retroviral infection producing AIDS.
AB  - LP-BM5 murine leukemia virus (MuLV) infection and cocaine administration are
      known to impair the murine immune system. We have developed a murine model to
      study the effect of daily cocaine administration and retrovirus infection on the
      lymphoid cell populations of the thymus. C57BL/6 female mice were studied
      following chronic cocaine administration for 11 weeks with simultaneous LP-BM5
      MuLV infection. Cocaine administration reduced body and thymus weight,
      significantly reduced the number of CD8+ cells in the thymus, and partially
      prevented thymus enlargement due to lymphoid cell proliferation induced by LP-BM5
      MuLV infection. Retrovirus infection was associated with a decrease in the
      percentage and absolute number of Thy 1.2+, CD4+, and CD8+ cells in the thymus,
      an effect potentiated by cocaine administration. Therefore cocaine impairs thymic
      function by altering the number of cells expressing T cell differentiation
      markers in MAIDS.

PMID- 1395124
TI  - Effects of rapamycin on human HLA-unrestricted cell killing.
AB  - Rapamycin (RAPA) is a potent immunosuppressant and can effectively prevent
      allograft rejection at a dosage 10- to 100-fold lower than that of cyclosporin A.
      RAPA strongly inhibits proliferation and function of T and B cells. In this
      study, we investigated the effect of RAPA on human HLA-unrestricted cell killing.
      It was shown that in vitro RAPA inhibited the cytolytic effect of natural killer
      cells and lymphokine-activated killer cells (LAK) and inhibited antibody
      dependent cell-mediated cytotoxicity. The effective concentration of RAPA was 10-
      to 100-fold higher than that required for inhibiting T cell proliferation. These
      results suggest that there could be a therapeutic dose window at which RAPA
      inhibits T cell activity while it leaves HLA-unrestricted cell killing
      unaffected. We also demonstrated that while IL4 inhibited LAK activity, and RAPA
      inhibited IL4-promoted T cell proliferation, RAPA was not able to antagonize
      IL4's inhibitory effect on LAK. This indicates that the mechanism of interaction
      between RAPA and IL4 on LAK is different from that on T cells.

PMID- 1395125
TI  - Treatment of coxsackievirus B3 myocarditis by immunoactive peptide in an animal
      model.
AB  - The effect of immunostimulant therapy on acute viral myocarditis, induced with
      coxsackievirus B3 (CB3), was investigated in C3H/He mice. Peritoneal exudate
      cells (PEC) or spleen cells (SC) from mice pretreated with a synthetic
      immunoactivating peptide FK565 significantly inhibited the multiplication of CB3
      in C3H/He mouse embryo fibroblast cells compared with PEC or SC from nontreated
      mice in vitro (6.45 +/- 0.20 log10 PFU/ml; control: 6.85 +/- 0.05, P < 0.05; 6.40
      +/- 0.07, control: 6.78 +/- 0.07, P < 0.05, respectively), although FK565 did not
      inhibit viral replication directly. Mice were inoculated intraperitoneally with 3
      x 10(5) plaque-forming units of CB3. FK565, 1 or 10 micrograms/kg, given
      intraperitoneally daily started on the same day of viral inoculation. To
      determine CB3 virus titer, mice were killed on Day 3. To study survival and
      myocardial histopathology, mice were killed on Day 20. Histopathological findings
      were scored on a scale of 0 to 4. FK565, 10 micrograms/kg/day, effectively
      inhibited myocardial viral replication (3.23 +/- 0.42 log10 PFU/mg, control: 3.71
      +/- 0.40, P < 0.05), reduced the cellular infiltration (1.3 +/- 0.7, control: 2.5
      +/- 0.5, P < 0.05), myocardial necrosis (1.4 +/- 0.9, control: 3.0 +/- 0.6, P <
      0.01), and calcification of the heart (1.0 +/- 0.6, control: 2.5 +/- 0.5, P <
      0.01) and increased survival (60%, control: 30%, P < 0.05). The present study
      suggests that immunostimulant therapy improves the course of viral myocarditis
      during the viral-mediated phase. The inhibitory activity of FK565 seems to be due
      to the activation of host defense mechanisms.

PMID- 1395126
TI  - Indications for the presence of antibodies cross-reactive with HTLV-I/II, but not
      HIV, in patients with myelodysplastic syndrome.
AB  - Serological evidence is presented for the fact that patients with the
      myelodysplastic syndrome exhibit a statistically significant reactivity in
      confirmatory assays for antibodies to human T-lymphotropic viruses types I and II
      (HTLV-I/II). This antibody reactivity, evident by indirect immunofluorescence and
      Western blot, was not confined to HTLV core antigens but extended to native and
      recombinant envelope glycoproteins. The effect was also observed in cases of
      acute myeloic leukemia, albeit to a lesser degree. It was essentially absent from
      patients with chronic myeloic leukemia or lymphocytic leukemias and healthy or
      multitransfused controls. No antibodies to human immunodeficiency viruses types 1
      or 2 were detected in any of the specimens. The investigated clinical population
      had no known risk factor for retroviral infection other than a history of
      multiple platelet transfusions, and none of the specimens was seropositive for
      HTLV-I or HTLV-II according to recommended criteria. The cause of this cross
      reactivity remains to be determined.

PMID- 1395127
TI  - Immunologic abnormalities in canine juvenile polyarteritis syndrome: a naturally
      occurring animal model of Kawasaki disease.
AB  - This study describes the immunologic abnormalities during the acute phase of
      juvenile polyarteritis syndrome (JPS), a multisystem necrotizing vasculitis of
      young dogs with a predilection for the coronary arteries. JPS has striking
      clinical, laboratory, and pathologic similarities to Kawasaki disease (KD), the
      most common cause of acquired heart disease in children in the United States. The
      immunologic abnormalities include an increase in serum IgA, an increase in the
      percentage of peripheral B cells and a decrease in the percentage of total
      peripheral T cells, a marked suppression of the blastogenic response to mitogenic
      stimulation, an inability to generate immunoglobulin-secreting plasma cells
      following polyclonal activation, the presence of antineutrophil cytoplasmic
      antibodies, and evidence of monocyte/macrophage activation. These
      immunoregulatory abnormalities are similar to those observed in children during
      the acute phase of KD. This unique, naturally occurring animal model of
      necrotizing vasculitis may prove useful for investigating novel therapeutic
      interventions in the treatment of necrotizing vasculitis and may yield insight
      into the immunopathology and etiology of KD.

PMID- 1395128
TI  - Idiotypic heterogeneity of VKIII autoantibodies to red blood cell antigens.
AB  - VKIII light (L) chains are commonly expressed by human autoantibodies with
      diverse binding specificities, including red blood cell antigens. To better
      understand the physiologic and pathologic expression of these L chain variable
      region genes, we have created a panel of murine monoclonal anti-idiotypic
      antibodies by immunization with a human lymphoblastoid B cell line that secretes
      an IgM VKIII autoantibody specific for the I red blood cell carbohydrate
      determinant. The binding specificities of these nine murine monoclonal
      antibodies, termed IV.1-IV.9, were evaluated against a large panel of monoclonal
      Ig proteins and compared to two previously well-characterized monoclonal anti
      idiotypes, 6B6.6 and 17.109; these two anti-idiotypes have been shown to
      primarily identify VKIII rheumatoid factors derived from the kv328 (VKIIIa) and
      kv325 (VKIIIb) genes, respectively. In contrast, our anti-idiotypic antibodies
      identified (public) cross-reactive idiotypes present on many VKIII proteins that
      included both anti-erythrocyte and rheumatoid factor autoantibodies. Certain anti
      idiotypic antibodies (IV.2 and IV.6) were restricted to VKIIIa L chains but
      differed from the 6B6.6 anti-idiotype by binding to a larger subset of VKIIIa
      proteins representing the products of at least two VKIIIa genes. One antibody of
      our panel (IV.5) recognized a private idiotope expressed only by the immunizing
      antibody. Using the panel of anti-idiotypic antibodies to evaluate erythrocyte
      autoantibodies with different serologic specificities, we found striking
      heterogeneity of L chain idiotype expression, even among known VKIII anti-i/I
      autoantibodies. These findings differ from the recently described structural and
      idiotypic conservation associated with the H chain of anti-i/I autoantibodies.
      From correlations of idiotypic reactivity with L chains of known sequence, it is
      postulated that the observed heterogeneity of L chain idiotype expression is due
      to differences in the genetic origin and/or somatic diversification of L chain
      variable region genes. Furthermore, subtle variability of L chain structure may
      contribute in part to the differences in fine binding specificity among anti-I
      and anti-i autoantibodies.

PMID- 1395129
TI  - Tumor necrosis factor production is deficient in diabetes-prone BB rats and can
      be corrected by complete Freund's adjuvant: a possible immunoregulatory role of
      tumor necrosis factor in the prevention of diabetes.
AB  - The Bio-Breeding (BB) rat develops spontaneous insulin-dependent diabetes
      mellitus (IDDM) and provides a useful animal model to study this human autoimmune
      disease. Treatment of BB rats with tumor necrosis factor (TNF) has been reported
      to prevent the development of IDDM. This suggests that deficient TNF production
      may be involved in the immunopathogenesis of autoimmune diabetes. In this study,
      we evaluated TNF production in diabetes-resistant (DR) BB rats, diabetes-prone
      (DP) BB rats, and DP BB rats protected from diabetes by the immunoadjuvant,
      complete Freund's adjuvant (CFA). TNF production in short-term cultures of
      peritoneal macrophages from DP rats was significantly less than that from control
      DR rats, both in the basal state and after stimulation with either interferon
      gamma (IFN-gamma) or lipopolysaccharide (LPS) in vivo and in vitro. In contrast,
      TNF production by macrophages from CFA-injected DP rats (basal and IFN-gamma or
      LPS-stimulated) was equal to or greater than that by macrophages from DP rats and
      similar to TNF production by macrophages from CFA-injected DR rats. These results
      suggest that development of autoimmune diabetes in BB rats may be causally
      related to deficient macrophage production of TNF, and that upregulation of TNF
      production may protect against diabetes development.

PMID- 1395130
TI  - Markers of inflammatory activation: upregulation of complement receptors CR1 and
      CR3 on synovial fluid neutrophils from patients with inflammatory joint disease.
AB  - Expression of the C3 receptors CR1 and CR3 was investigated on neutrophils from
      paired peripheral blood and synovial fluid samples from 34 patients with
      inflammatory joint disease (21 patients with rheumatoid arthritis (RA) and 13
      patients with other articular diseases (OAD)). Using monoclonal antibodies (anti
      CD35, anti-CD11b) and immunofluorescence flow cytometric analyses the percentages
      of positively labeled cells and the relative fluorescence intensities (as a
      measure of receptor number) were determined. CR1 and CR3 were found to be present
      on the majority (> 85%) of circulating neutrophils from normal subjects, RA and
      OAD patients, and on synovial fluid neutrophils from both patient groups. A
      strong correlation between neutrophil CR1 and CR3 expression was observed in
      peripheral blood samples from normal subjects (r = 0.81; P = 0.001), RA (r =
      0.79; P = 0.001), and OAD patients (r = 0.83; P = 0.001); in each case the levels
      of CR3 expression were approximately twice those recorded for CR1. Both CR1 and
      CR3 expression was upregulated on synovial fluid neutrophils compared with that
      observed on the corresponding peripheral blood cells. Mean percentage increases
      observed were: RA patients: CR1, 16.5% (P < 0.001) and CR3, 28.7% (P < 0.001);
      and OAD patients: CR1, 4.1% and CR3, 26.9% (P = 0.001). Correlation of serum and
      synovial fluid IL-6, IL-8, and immune complex levels with neutrophil CR1 and CR3
      expression failed to demonstrate any significant relationship between the
      concentrations of these soluble factors and receptor expression. Upregulation of
      CR1 and CR3 receptors, reflecting neutrophil activation within the inflamed
      joint, is a consistent finding in patients with inflammatory arthropathies.

PMID- 1395131
TI  - Identification of autoantigen recognized by autoimmune ophthalmopathy sera with
      immunoblotting correlated with orbital computed tomography.
AB  - We have demonstrated that there is an antibody related to extraocular muscle
      enlargement in autoimmune ophthalmopathy (Graves' ophthalmopathy, thyroid
      associated correlated with orbital computed tomography (CT). This study was
      designed to identify the autoantigen and to determine whether there are common
      antigens among the extraocular muscle, the lacrimal gland, and the thyroid. We
      prepared a 100,000g sediment fraction of porcine extraocular muscle, lacrimal
      gland, thyroid, and human thyroid, followed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting with sera from
      patients with Graves' disease, with or without ophthalmopathy, classified by
      symptoms and signs combined with orbital CT and normal controls. The results
      showed there was an approximately 55-kDa protein band which was recognized by the
      sera in 32.1% (9/28) of patients with autoimmune ophthalmopathy and in 47.3%
      (9/19) of patients with extraocular muscle enlargement demonstrated by orbital
      CT. It was significantly higher than the positive rates in patients without
      autoimmune ophthalmopathy and normal controls (15.8 and 11.1%, respectively, P <
      0.025). However, there was no common antigen among the extraocular muscles, the
      lacrimal gland, and the thyroid. To further confirm this eye muscle-specific
      antigen, the approximately 55-kDa protein band was cut and solubilized from the
      nitrocellulose paper after SDS-PAGE, and electrophoretically transferred and used
      as an antigen in enzyme-linked immunosorbent assay. The absorbance was
      significantly higher in patients with autoimmune ophthalmopathy than patients
      without ophthalmopathy (P < 0.005), and normal controls (P < 0.01). Our findings
      suggest that an approximately 55-kDa protein may be a possible antigen in the eye
      muscle related to autoimmune ophthalmopathy.

PMID- 1395132
TI  - Human anti-F(ab')2 antibodies show preferential reactivity for F(ab')2 molecules
      bearing lambda light chains.
AB  - In order to evaluate binding specificities of anti-F(ab')2 antibodies from
      patients with systemic lupus erythematosus (SLE) and from normal healthy
      controls, F(ab')2 fragments were prepared from 24 IgG myelomas with defined
      isoelectric points, DNA-associated idiotypes, and kappa/lambda light chain types.
      Using ELISA and hemagglutination assays, anti-F(ab')2 antibodies from 12 healthy
      controls and 29 SLE patients were observed to exhibit preferential binding
      (lambda > kappa) to myeloma F(ab')2 fragments composed of lambda light chains (P
      < 0.0001). No correlation of anti-F(ab')2 binding and presence of cationic,
      neutral, or anionic isoelectric points or for DNA-associated idiotypes on
      monoclonal F(ab')2 was detected. Anti-F(ab')2 antibodies, often elevated in SLE
      during remission, show preferential specificity for F(ab')2 fragments bearing
      lambda light chains.

PMID- 1395133
TI  - Lessons from animal models: the scope of mercury-induced autoimmunity.

PMID- 1395134
TI  - Possible supplemental mechanisms in the pathogenesis of AIDS.
AB  - Multiple and diverse mechanisms have been proposed as supplements to the HIV-1
      virus in the destruction of CD4+ cells and the pathogenesis of AIDS. But it is
      now realized that 100 times more CD4+ cells are infected with HIV-1 than was
      originally thought to be the case, and many antigen-presenting cells are infected
      as well. In addition to the direct cytopathic effect of the virus, one or a few
      supplemental mechanisms may well suffice to explain the progressive loss of CD4+
      cells, e.g., the considerable variation in the virus and/or the destruction of
      uninfected CD4+ cells by one immunological mechanism or another. However, it is
      not yet possible to state confidently which additional mechanism(s) is important.
      Identification of the nature of this supplemental process has become essential
      for successful, nonharmful intervention.

PMID- 1395135
TI  - Murine susceptibility to mercury. I. Autoantibody profiles and systemic immune
      deposits in inbred, congenic, and intra-H-2 recombinant strains.
AB  - Inbred, congenic, and intra-H-2-recombinant mouse strains were given subcutaneous
      injections of either 1.6 mg HgCl2/kg body wt or 0.1 ml NaCl thrice weekly for 5-6
      weeks. Mercury-treated mice from strains carrying the H-2s haplotype developed
      antinucleolar antibodies (ANoA), which targeted the 34-kDa nucleolar protein
      fibrillarin, and in some instances also nucleolar proteins of 60-70 and 10-15
      kDa, the latter corresponding to histones. Strains with H-2b and H-2d haplotypes
      were resistant to induction of ANoA. The susceptibility to development of
      AnoA/antifibrillarin antibodies (AFA) was mapped to the H-2A-region using intra-H
      2-recombinant strains. We were not able to confirm earlier reports that
      expression of H-2E genes dampens the development of ANoA. Mercury treatment
      caused a substantial increase in the titer of antichromatin (ACA) and/or
      antihistone (AHA) antibodies in a fraction of SJL/J, A.SW, A.TH, B10.S, and
      B10.HTT mice (H-2s), and in A/J (H-2k) mice, whereas mice from the C57BL/6J and
      C57BL/10J (H-2b), and the DBA and BALB/c (H-2d) strains were low or
      nonresponders. The development of AHA and ACA could not be linked to the H-2
      complex. A significant, substantial increase of granular mesangial and systemic
      vessel wall IgG deposits occurred in mice with serum ANoA/AFA. However, the
      B10.S(9R) and B10.HTT strains, which express the H-2E genes, developed only an
      intermediately increased titer of mesangial IgG deposits. Systemic vessel wall
      IgG deposits occurred in only 60-80% of the B10.S(9R) mice and in none of the
      B10.HTT mice. This contrasted with the high titer of mesangial IgG deposits and
      uniform development of systemic vessel wall IgG deposits observed in B10.S mice
      not expressing H-2E. Mice with mesangial IgG deposits showed a mild
      glomerulonephritis. There was no systemic vasculitis. The susceptibility to
      development of ANoA, AHA, ACA, and systemic, granular IgG deposits in the B10.S
      strain was influenced by the sex, since males showed less uniform development of
      these immunopathologic features than females.

PMID- 1395136
TI  - Introduction: a tribute to David L Nanney, an experimental ciliatologist.

PMID- 1395137
TI  - Pheromone 4 gene of Euplotes octocarinatus.
AB  - We have cloned and sequenced a 1.7 kb macronuclear chromosome encoding the
      pheromone 4 gene of Euplotes octocarinatus. The sequence of the secreted
      pheromone is preceded by a 42 amino acid leader peptide, which ends with a lysine
      residue. The sequence coding for the leader peptide contains information for a
      putative signal peptide and is interrupted by a 772 bp intron as shown by
      comparison with a cDNA clone. A 64 bp intron and a 145 bp intron interrupt the
      sequence coding for the secreted pheromone. The three introns contain typical 5'
      and 3' splice junctions and a putative branch point site. The small introns have
      a low GC content. The large intron has a GC content similar to that of the
      pheromone 4 gene exons. The amino acid sequence of pheromone 4, deduced from both
      the genomic DNA and the cDNA of pheromone 4, shows that the secreted pheromone
      consists of 85 amino acids. One of its amino acids is encoded by a UGA codon.
      Since it has been shown for pheromone 3 of E. octocarinatus that UGA is
      translated as cysteine, it is assumed that the UGA codon encodes cysteine in
      pheromone 4 as well. The 164 bp noncoding region upstream of the leader peptide
      is AT-rich and contains an inverted repeat capable of forming a stem-loop
      structure with a stem of 11 bp. The 151 bp noncoding region at the 3' end of the
      chromosome contains a putative polyadenylation sequence and an inverted repeat.
      The macronuclear molecule is flanked by telomeres and carries the pentanucleotide
      motif TTGAA, located at a distance of 17 nucleotides from the telomeres. This
      motif has been suggested to be involved in the formation of macronuclear
      chromosomes.

PMID- 1395138
TI  - Ciliary polypeptides and glycoconjugates of wild-type and mutant Tetrahymena
      thermophila: starved versus nonstarved.
AB  - To investigate the role of cilia in mating interactions of Tetrahymena
      thermophila, ciliary membrane-rich fractions were isolated from two wild-type
      strains, a non-discharge mucocyst mutant which possesses mating behavior similar
      to wild-type, and a mating mutant which is able to costimulate cells of
      complementary mating type but cannot enter into pair formation. In each case,
      proteins from the ciliary membrane-rich fractions of starved, mating-competent
      ("initiated") cells were compared with those from non-starved, mating-incompetent
      ("non-initiated") cells, by gel electrophoresis and lectin blotting. In stained
      gels, a 43 kDa polypeptide was reduced or absent in initiated cells but present
      in non-initiated cells, in all strains. In silver-stained gels, a 25 kDa
      polypeptide was present in all strains, both initiated and non-initiated. In
      blots probed with Con A-peroxidase, a 25 kDa glycoprotein was present in ciliary
      membrane fractions from non-initiated cells and absent in membranes of initiated
      cells of the two wild-type strains and the mucocyst mutant, but is present in
      initiated and non-initiated cells of the mating mutant (several hypotheses are
      presented to explain these findings). In addition, ciliary proteins of the mating
      mutant included at least two unique Con A-binding polypeptides. Our results
      support the idea that development of mating competence during starvation involves
      an extensive remodeling of ciliary membranes, and identify a 25 kDa
      glycoconjugate as having a potential role in control of pair formation during
      mating.

PMID- 1395139
TI  - Mapping the mating type locus of Tetrahymena thermophila: meiotic linkage of mat
      to the ribosomal RNA gene.
AB  - Tetrahymena thermophila has a multiple mating type system. While a sexually
      mature cell usually expresses only one mating type, its germline (micronucleus)
      carries the genetic potential for 5 to 7 mating types. The set of allowed mating
      types is specified by the mat locus. The choice of which particular mating type
      is expressed by a cell reflects a somatically inherited, developmentally
      programmed differentiation of the somatic nucleus (macronucleus). In this work we
      report that the mat locus maps to the left arm of chromosome 2, as determined by
      nullisomic deletion mapping. We also report a distance of 29 cM between the mat
      locus and the ribosomal RNA gene, previously mapped to chromosome 2L. This
      represents another (rare) case of meiotic linkage in Tetrahymena.

PMID- 1395140
TI  - Development of sexual maturity in the ciliate Euplotes crassus: sources of
      variation in the timing of maturity.
AB  - The life styles of ciliated protists are particularly suitable for experimental
      analyses of certain aspects of developmental and genetic biology. The progression
      from sexual immaturity to maturity to senescence represents one of the most
      intriguing aspects of developmental programs. The extent to which progeny clones,
      their subclones, and testers used in the assay result in different lengths of
      immaturity has been investigated in Euplotes crassus. Six subclones from each of
      12 progeny clones from a cross between stocks EC1 and EC2 were tested for
      maturity with stocks EC3, EC4, and EC5 on every transfer. Analysis of variance
      was used to partition the total variation in fissions to maturity into parts due
      to clones, subclones, and testers and the interactions between these levels. The
      error, interaction of subclones and testers, corresponds to a standard deviation
      of only 4.1 fissions, while the within clone within tester means range from 15.2
      to 46.7 fissions; all levels except testers contribute significantly to the total
      variation. Most of the variability is attributable to clones (66%), the next most
      to error (16%), the next most to interaction of clones by testers (13%), and the
      least to subclones (5%). An a posteriori analysis examined whether the
      differences among clones were due to the cytoplasm of the clone ancestor
      (exconjugant), its mat (mating-type) locus genotype, or the mated pair it came
      from. None of these characteristics was able to interpret simply the large
      variability among clones. These results provide evidence that the transition from
      immaturity to maturity is quantitative and complex rather than a jump from one
      well-defined state to another.

PMID- 1395141
TI  - Suicide is not the inevitable outcome of "perpetual" selfing in tetrahymenines
      collected from natural habitats.
AB  - A significant fraction of the Tetrahymena clones isolated from natural habitats
      self (mating occurs within a clone). Early attempts to study such clones failed
      because stable subclones were rarely, if ever, observed, and isolated pairs all
      died. Isozyme analysis revealed that these wild selfers were a diverse group;
      some were very similar to T. australis, a species with synclonal mating type
      determination and to T. elliotti, shown recently to have a karyonidal mating type
      system. One originally stable clone of T. australis included some selfing clones
      after a few years in our laboratory. Other clones manifested unique zymograms.
      Subclones isolated from 18 selfer strains were heterogeneous. All subclones of
      several selfers mated massively at each transfer through 100 fissions. Selfing
      among subclones of other selfers was highly variable or not observed. Although
      77% of the pairs isolated died, and 9% of the pair cultures selfed, 15 selfers
      yielded some viable nonselfing "immature" progeny. Additional immature progeny
      were obtained by isolating pairs from macronuclear retention synclones. Although
      some "immature" progeny eventually selfed, most remained stable. Giemsa staining
      revealed macronuclear anlagen in nearly all mating pairs and some anomalies.
      Crosses among the F1 progeny clones of the T. elliotti selfers yield viability
      data comparable to those from crosses among normal strains. Perhaps perpetual
      selfing is a mechanism of getting rid of deleterious combinations of genes and
      uncovering better combinations in homozygous state by playing genetic roulette.

PMID- 1395142
TI  - Developmental expression of macronuclear specific antigen in Paramecium caudatum.
AB  - We obtained a monoclonal antibody (MA-1) specific for macronuclei of the ciliate
      Paramecium caudatum and P. dubosqui. Immunoblotting showed that the antigen was a
      polypeptide of 50 kilodalton (kDa). During the process of nuclear differentiation
      in P. caudatum, the MA-1 antigens appeared in the macronuclear anlagen
      immediately after four out of eight post zygotic nuclei differentiated
      morphologically into the macronuclear anlagen. Afterwards, the antigens could be
      detected in the macronucleus through the cell cycle, and disappeared when the
      macronucleus began to degenerate in exconjugant cells. These results suggest that
      the antigens may play a role in the differentiation and function of the
      macronucleus.

PMID- 1395143
TI  - Mutation affecting cell separation and macronuclear resorption during conjugation
      in Tetrahymena thermophila: early expression of the zygotic genotype.
AB  - A new recessive conjugation lethal mutation was found in Tetrahymena thermophila
      which was named mra for macronuclear resorption arrest. Other events affected by
      the mra mutations are separation of pairs, DNA replication in the macronuclear
      anlagen, and resorption of one of the two micronuclei. In wild-type crosses 50%
      of the pairs had separated by 12 hr after mixing two mating types and had
      completed resorption of the old macronucleus 1-2 hr later. In contrast most mra
      conjugants did not separate even by 24 hr after mixing and the old relic
      (condensed) macronucleus was seen in over 90% of them. After addition of 10 mM
      calcium to the conjugation medium, the mra conjugants did separate but they still
      failed to complete resorption of the old macronucleus and to replicate
      macronuclear anlagen DNA in the exconjugants. The calcium induced separation of
      the mra conjugants occurred later than the separation of control pairs. During
      normal conjugation cell separation occurs before the first expression of known
      macronuclear genes and prior to processing of the macronuclear DNA. Therefore,
      the mra phenotype infers that separation of conjugants requires a signal which is
      produced by the macronuclear anlagen at an unusually early time.

PMID- 1395144
TI  - Scrambled actin I gene in the micronucleus of Oxytricha nova.
AB  - In the hypotrichous ciliate Oxytricha nova the cloned precursor gene from the
      micronuclear genome that encodes actin I is composed of highly disordered blocks
      of deoxynucleotide sequences. We present and illustrate in detail a recombination
      model that explains how the actin I gene may be unscrambled during macronuclear
      development after cell mating. The model was described in a previous publication
      (Greslin et al.: Proc Natl Acad Sci USA 86:6264-6268, 1989). Here we show the
      data, described in the earlier publication, that support the model. The data show
      that scrambling is not an artifact of cloning. They rule against the presence of
      an unscrambled copy of the actin I gene in the micronucleus, which means that
      unscrambling must be a part of macronuclear development. Finally, the data prove
      that the actin I gene in O. trifallax is scrambled in a pattern that resembles
      the pattern in O. nova.

PMID- 1395145
TI  - Tetrahymena telomerase RNA levels increase during macronuclear development.
AB  - Telomeres, the G-rich sequences found at the ends of eukaryotic chromosomes,
      ensure chromosome stability and prevent sequence loss from chromosome ends during
      DNA replication. During macronuclear development in Tetrahymena, the chromosomes
      fragment into pieces ranging from 20 kb to 1,500 kb. Tetrahymena telomerase, a
      ribonucleoprotein, adds telomeric (TTGGGG)n repeats onto telomeres and onto the
      newly generated macronuclear DNA ends. We have investigated whether telomerase
      RNA levels increase during macronuclear development, since such an increase might
      be expected during chromosomal fragmentation. The steady-state level of the
      telomerase RNA component was used to estimate the abundance of telomerase present
      in mating and nonmating Tetrahymena. Northern blot analysis revealed that in
      vegetatively growing Tetrahymena, there were 18,000-40,000 copies of telomerase
      RNA per cell. In mating cultures, the levels of RNA increased 2- to 5-fold at 9
      15 h, and 1.5- to 3.5-fold in starved nonmating cultures. This increase in
      telomerase RNA paralleled telomerase activity, which also increased slightly in
      mating and starved nonmating cells.

PMID- 1395146
TI  - Stochastic developmental variation in the ratio of allelic rDNAs among newly
      differentiated, heterozygous macronuclei of Tetrahymena thermophila.
AB  - Ciliates possess nuclear dimorphism, i.e., they carry two structurally and
      functionally differentiated types of nuclei. The micronucleus and macronucleus
      serve as the germline and somatic nuclei, respectively, of the cell. The
      macronucleus differentiates from a mitotic sister of the micronucleus once per
      life cycle. Macronuclear differentiation is accompanied by a developmentally
      programmed set of DNA rearrangements, including chromosome fragmentation,
      telomere addition, and amplification. Given the diploidy of the MAC anlage, are
      both homologous copies of a chromosome processed and amplified equally and
      simultaneously in an individual differentiating MAC? We have approached this
      question for the case of the rDNA, exploiting previously identified DNA
      polymorphisms and the sensitivity of PCR. We determined allelic ratios in
      individual caryonide cells, i.e., the cells carrying the primary products of MAC
      differentiation, prior to the first division of the newly differentiated MAC. We
      observed stochastic variability in allelic ratios among caryonides that start
      with genetically identical heterozygous MACs. Either rDNA type can be in the
      majority. Appropriate controls make it unlikely that the ratios observed were
      significantly affected by variation in the assay itself. The variability may well
      result from the statistical variation associated with the relative timing of
      individual biochemical events initiating the processing and/or amplification of a
      few rDNA precursor molecules, presumably 4-8 at the most, in a MAC anlage. In
      addition to this stochastic variability, we observed a small but distinct bias in
      favor of the C3 rDNA. Thus the replication advantage of C3 relative to B rDNA in
      heterozygous MACs, previously detected during vegetative multiplication, may
      begin to be expressed during developmental amplification.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1395147
TI  - Developmental analysis of the cell recognition mechanism in the ciliate Euplotes
      raikovi.
AB  - Euplotes raikovi, like other ciliates, passes through a postconjugal immaturity,
      operatively identified by an apparent cell inability to form mating pairs under
      experimental conditions that are the same as those used for inducing mating at
      maturity. In cells homozygous for the gene mat-2, which controls the pheromone Er
      2, Er-2 mRNA synthesis and mature Er-2 secretion were shown to start from the
      very beginning of the life cycle and continue throughout immaturity, although to
      extents estimated to be 5- to 10-fold lower than at maturity. In addition,
      experiments of 125I-Er-2 binding and crosslinking provided evidence that
      autocrine pheromone-binding sites, showing values of the dissociation constant of
      the order of 10(-9) M, are on the surface of immature cells. The number of these
      sites per cell was estimated to increase from less than 10(6) per cell of 5-7
      fissions of age, to about 16 x 10(6) at maturity. These results were taken to
      suggest that a pheromone-receptor production is stimulated during immaturity by
      autocrine pheromone binding to cells and that this production might be essential
      for the development of a pheromone-receptor density high enough to transform the
      cell from "immature" to "adult," that is competent to respond as well to
      pheromones of conspecific, genetically different cells.

PMID- 1395148
TI  - Looking ahead: an interview with Claire M. Fagin.

PMID- 1395149
TI  - Periorbital hemangiomas.
AB  - 1. Any hemangioma that involves the upper or lower lid and leads to partial
      closure in infancy may interfere with or prevent development of normal binocular
      vision in a matter of days to weeks. 2. Hemangiomas least likely to interfere
      with vision are lower lid lesions occupying one third of the lid margin or less,
      not extending beyond the eyelid region, and resolving early. 3. Hemangiomas
      associated with deprivation amblyopia (with or without anisometropia) are lesions
      occupying more than one half of the lid margin, extending beyond the eyelid
      region, resolving late, and obstructing the visual axis. 4. Hemangiomas
      associated with isolated anisometropic amblyopia are local but bulky lesions that
      are usually but not always restricted to the upper lid, closing the eye partly
      and resolving late. 5. The treatment of choice for periorbital hemangiomas is
      corticosteroids, either systemic or intralesional.

PMID- 1395150
TI  - Ocular melanoma.
AB  - Ocular melanomas are the most common intraocular malignancy in adults. The
      majority of ocular melanomas are choroidal melanomas. These tumors can be
      difficult to diagnose, especially when they are small. Documented growth of a
      lesion on serial examinations is the most important clinical feature favoring the
      diagnosis of a choroidal melanoma. Diagnostic studies including ultrasonography
      and angiography may be helpful in the diagnosis of these tumors. A number of
      treatment options are available for choroidal melanomas. These include
      photocoagulation, radiation therapy, local tumor resection, and enucleation.

PMID- 1395151
TI  - Periocular tumors.
AB  - Next to the fear of death from cancer, patients fear loss of sight more than
      anything else. They are especially fearful of the potential for visual impairment
      when confronted with the need to treat an eyelid neoplasm. Patients need
      reassurance that the treatment will not compromise vision and that their visual
      needs will be attended to. Optimally, the responsibilities for patient management
      are coordinated and shared in a team approach. Although many tumors around the
      eye are easily managed, a large proportion of them are significant by virtue of
      their size and location. These are best treated by a team that is prepared to
      provide optimal assessment, can deal with any size lesion and its repair, and is
      familiar with the spectrum of complications and their management.

PMID- 1395152
TI  - Lasers in dermatology and ophthalmology.
AB  - Dermatology and ophthalmology are two specialties that have made exceptional use
      of laser technology. In dermatology, port wine stains and hemangiomas, neoplastic
      lesions, and adnexal tumors are amenable to laser treatment. In ophthalmology,
      the use of lasers to effect photocoagulation, photoradiation, photovaporization,
      photodisruption, and photodecomposition has permitted the treatment of vascular
      retinal disease, macular edema, intraocular tumors, open angle glaucoma, and
      angle closure glaucoma. Although great strides in laser technology have been
      made, the future is even more promising as laser devices are further modified to
      treat specific disease processes.

PMID- 1395153
TI  - Regional anesthesia of the eye and orbit.
AB  - The principles and techniques of providing topical and regional anesthesia to the
      eye are presented in this article. Potential complications and their treatments
      are outlined, with special emphasis placed on the characteristics of the
      oculocardiac reflex.

PMID- 1395154
TI  - Oculocutaneous manifestations observed in multisystem disorders.
AB  - Patients with multisystem disorders frequently present with or eventually
      manifest cutaneous disease. Many of these patients will also manifest ocular
      changes. In these disorders, the dermatologist or ophthalmologist may act as
      primary provider or consultant. Thus, familiarity with these conditions will
      enable the specialist to provide better care for these patients. This article
      reviews the oculocutaneous manifestations of sarcoidosis, Behcet's disease,
      Reiter's syndrome, and Sjogren's syndrome.

PMID- 1395155
TI  - Metabolic disease.

PMID- 1395156
TI  - Ocular and periocular infections.
AB  - The eye is an important site for infectious disease because an incorrect
      diagnosis can cause loss of vision or loss of life. An approach to accurate
      diagnosis, intervention, and therapy is outlined.

PMID- 1395157
TI  - Lyme disease.
AB  - Lyme disease is a multisystem disorder caused by the spirochete Borrelia
      burgdorferi. It is transmitted to human and animal hosts primarily by ticks of
      the Ixodes ricinis complex. Recognition of its characteristic skin and eye
      manifestations facilitates diagnosis and treatment.

PMID- 1395158
TI  - Acquired immunodeficiency syndrome and the eye.
AB  - Patients with AIDS or ARC may develop ocular manifestations falling in four broad
      categories: (1) conjunctival and periorbital disease, (2) neuro-ophthalmologic
      abnormalities, (3) retinal microangiopathy, and (4) opportunistic retinal and
      choroidal infections. Careful ophthalmologic examination generally permits
      identification and differentiation of these entities. Although ocular involvement
      is frequently a harbinger of an unfavorable systemic prognosis, specific drug
      therapy may be of some benefit in arresting disease in selected individuals.
      Further advances in the diagnosis and treatment of AIDS-related ocular tumors and
      infections may improve the quality of life for these patients.

PMID- 1395159
TI  - Physical and chemical injuries of the eyes and eyelids.
AB  - Ocular trauma is not uncommon. Because the tissues associated with visual
      function are delicate and remarkably specialized, care of ocular injuries is best
      left to well-trained specialists. Initial care, however, is often simply common
      sense. Irrigation of chemical burns, sterile techniques, and procedures that
      salvage tissue are good general principles.

PMID- 1395160
TI  - Eyebrow loss, eyelash loss, and dermatochalasis.
AB  - The eyebrows, eyelashes, and eyelids are important protective structures for the
      eye and are also of considerable cosmetic value. The dermatologist should
      understand the available cosmetic and surgical techniques for helping patients
      with eyebrow loss, eyelash loss, and dermatochalasis.

PMID- 1395161
TI  - Increased aggregation with normal surface charge and deformability of red blood
      cells in children with nephrotic syndrome.
AB  - Hemorheological risk factors for thromboembolic disease were evaluated in 25
      pediatric patients with idiopathic nephrotic syndrome (NS). In patients with
      increased proteinuria (greater than 100 mg/m2/24 h) red blood cell (RBC)
      aggregation and plasma viscosity were significantly increased when compared with
      patients in remission (less than 100 mg/m2/24 h) and with healthy controls. RBC
      surface charge was normal during increased proteinuria and remission. RBC
      aggregation correlated positively with plasma viscosity, fibrinogen, alpha 2
      macroglobulin, immunoglobulin M, and the degree of proteinuria, and negatively
      with plasma albumin levels. RBC aggregation showed no correlation to RBC surface
      charge. Hematocrit and RBC deformability (rheoscope) were similar in both patient
      groups and in controls. Increased RBC aggregation and plasma viscosity may
      contribute to the increased risk of venous thromboembolism in NS.

PMID- 1395162
TI  - Spontaneously remitting minimal change nephropathy preceding a relapse of
      Hodgkin's disease by 19 months.
AB  - A 35-year-old women was diagnosed as suffering from Hodgkin's disease,
      lymphocytic predominant, based on a biopsy of an enlarged axillary lymph node.
      She was classified as stage IIA. Subtotal nodal irradiation resulted in a full
      remission. Ten months later she presented with a full blown nephrotic syndrome.
      Renal biopsy disclosed minimal change nephropathy. Despite extensive
      investigation no evidence of a relapse of the lymphoma was found. Whilst
      undergoing the investigation her proteinuria began to decrease and during the
      next 5 months it totally disappeared with no specific treatment being
      administered. Fourteen months after complete cessation of the proteinuria a left
      parasternal mass appeared. Biopsy confirmed a relapse of Hodgkin's lymphoma. The
      patient fully responded to chemotherapy and local irradiation. Noticeably, during
      the relapse and currently after a 3.5 year follow up period the patient has
      remained free of proteinuria. A review of the literature yielded altogether 14
      cases in which the course of minimal change nephropathy did not run in parallel
      to that of the lymphoma. These are discussed in detail.

PMID- 1395163
TI  - Combined liver kidney transplantation in primary hyperoxaluria type I. Prevention
      of the recidive of calcium oxalate deposits in the renal graft.
AB  - We report the case of a 31-year-old patient who underwent combined liver and
      kidney transplantation for primary hyperoxaluria type I. Intensive hemodialysis
      was performed before the intervention and post-operatively in order to maintain
      plasma oxalate levels near the normal range. In spite of the correction of the
      liver enzyme deficiency, oxalate removal from the tissular stores led to
      prolonged hyperoxaluria, more longer than one year after the transplantation, as
      already reported. This increased urinary oxalate excretion exposes the renal
      graft to the risk of recurrence of calcium oxalate deposits and stone formation
      during a prolonged period. Hemodialysis in the postoperative period and fluid
      intake allowing a large urine volume might be able to decrease the concentration
      of urinary oxalate under the critical value of 300 mumol/l, at which
      supersaturation of urine in respect of calcium oxalate occurs.

PMID- 1395164
TI  - Risks and benefits of graft biopsy in renal transplantation under cyclosporin-A.
AB  - 261 patients who received a kidney transplant under cyclosporin-A
      immunosuppression were reviewed in order evaluate the benefits and the risks of
      renal graft biopsies. 240 graft biopsies were performed in 124 of the 261
      patients. The biopsy diagnoses were 103x rejection, 90x cyclosporin-A toxicity,
      8x acute tubular necrosis, 8x glomerulonephritis, 9x different biopsy results,
      and 12 cases of normal renal tissue. In 214 cases the clinical course was well
      explained by the biopsy result. The histological results led to therapeutical
      changes in 199 cases. 221 of the 240 biopsies were performed without any
      complications. There was only one biopsy with irreversible and there were 19
      biopsies with reversible complications.

PMID- 1395166
TI  - Renal biopsy diagnosis of acute lymphocytic leukemia.
AB  - Hyperuricemia, due to inborn errors of metabolism, dehydration, or tumor lysis,
      may cause renal insufficiency. Hyperuricemia from tumor lysis syndrome in
      malignancy is usually associated with electrolyte disturbances such as
      hyperkalemia, hyperphosphatemia or hyper or hypocalcemia. Tumor infiltration into
      the kidneys can occur, yet this accounts for renal insufficiency in only 1% of
      patients. This infiltration of tumor cells into the kidneys is usually associated
      with evidence of malignancy elsewhere as identified by physical exam,
      radiographic studies, and examination of the peripheral smear or bone marrow. We
      report an unusual presentation of a child with acute lymphocytic leukemia
      presenting with acute renal failure, nephromegaly and hyperuricemia without
      electrolyte disturbances or systemic evidence of tumor elsewhere. We stress the
      importance of kidney biopsy in order to identify the etiology of the renal
      failure and hyperuricemia.

PMID- 1395165
TI  - Complications of percutaneous renal biopsy: a review of 37 years' experience.
AB  - Over a period of 37 years we performed renal biopsies 1812 times in 1638
      subjects. Tissue adequate for interpretation was obtained in 1593 subjects (88%).
      Complications occurred in 7% of the total biopsies performed, consisting of gross
      hematuria lasting for more than 12 hours (3%), pain lasting for more than 12
      hours (4%), a palpable hematoma (1%), infection (0.2%), and death (0.2%).
      Complications were higher when the biopsy yielded unsatisfactory samples (9.5%),
      although there were no deaths. Complications were not related to age but an
      elevated BUN appeared to be associated with a higher rate of complications,
      although this was not statistically significant. Deaths appeared to occur at
      unpredictable intervals and in retrospect could not have been foreseen.

PMID- 1395167
TI  - Acute effect of dialysate calcium concentration and intravenous vitamin D3 on the
      secretion of parathyroid hormone in hemodialysis patients.
AB  - We studied the suppression of intact parathyroid hormone (PTH) in ten patients on
      chronic hemodialysis using different calcium concentrations of dialysate.
      Secondly, giving i.v. vitamin D3 at commencement of dialysis we investigated
      whether 1 alpha (OH)D3 or 1,25(OH)2D3 acutely modifies the responsiveness of the
      parathyroid gland to the suppressive effect of increased serum calcium. Dialysis
      with high-calcium dialysate (1.75 mmol/l) reverted the plasma PTH to normal
      limits. Lower-calcium dialysate (1.5 mmol/l) induced only a partial suppression
      of hyperparathyroidism. We found no differences in the suppression of
      hyperparathyroidism whether 1 alpha (OH)D3 or 1,25(OH)2D3 was given at the
      beginning of the dialysis or not. We conclude that the suppressibility of
      hyperparathyroidism in dialysis patients can be evaluated by different calcium
      concentrations of dialysate, and that i.v. vitamin D3 does not acutely modify the
      responsiveness of the parathyroid gland to the effect of calcium.

PMID- 1395168
TI  - Total and regional bone mineral density by dual photon absorptiometry in patients
      on maintenance hemodialysis.
AB  - To evaluate bone loss in renal osteodystrophy, we measured total and regional
      (head, trunk, pelvis, leg and arm) bone mineral density (BMD) by dual photon
      absorptiometry in 72 patients on maintenance hemodialysis (HD). We also examined
      the validity of serum carboxy-terminal parathyroid hormone (C-PTH) and intact-PTH
      as an indicator of secondary hyperparathyroidism. Total BMD correlated inversely
      with age in female patients (r = -0.57, p less than 0.01), but not in male
      patients. Female patients older than 50 years were omitted from analysis to
      exclude the effect of menopause on bone. Among clinical and biochemical
      parameters, only trunk BMD correlated inversely with the duration of HD (r = 
      0.26, p less than 0.05). Head, trunk and total BMD correlated inversely with
      serum alkaline phosphatase, C-PTH and intact-PTH, while pelvis BMD did not. Leg
      and arm BMD also correlated inversely with serum intact-PTH, but not with serum C
      PTH. The serum level of C-PTH correlated positively with the duration of HD (r =
      0.40, p less than 0.005), while intact-PTH did not. As compared with 18 control
      male volunteers aged 25-42 years, trunk, pelvis, leg, arm and total BMD were
      significantly lower in male patients on HD aged 22-49 years, whereas head BMD did
      not differ significantly between the two groups. The percent decrease of BMD was
      most prominent in the trunk (-19.6%, p less than 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1395169
TI  - A two-site immunochemiluminometric assay for intact parathyroid hormone and its
      clinical utility in hemodialysis patients.
AB  - Measurement of serum parathyroid hormone (PTH) concentrations is complicated by
      the fact that there are several fragments of the hormone in the circulating as a
      result of the metabolism of PTH. The best way to study the secretory activity of
      the parathyroid glands directly may be to measure the biologically active intact
      PTH molecule. Recently, it has become possible to overcome these limitations by
      application of the two-site immunoradiometric assay (IRMA) to the measurement of
      intact PTH. The two-site immunometric technique has been applied to the two-site
      immunochemiluminescent assay (ICMA) for the measurement of circulating intact
      PTH. To evaluate the utility of measurements of serum intact PTH by two-site ICMA
      in hemodialysis patients, two-site ICMA and IRMA were compared in 104
      hemodialysis patients. We found a good correlation (r = 0.93) between values
      obtained by ICMA and by IRMA. Although serum intact PTH by ICMA was significantly
      suppressed by rising plasma ionized calcium after a session of hemodialysis in 29
      patients, mid-region PTH did not show a significant change. This result suggests
      the intact PTH assay is more suitable for the earlier detection of secondary
      hyperparathyroidism than the mid-region assay and may be useful for precise
      assessment of clinical status and response to therapeutic intervention designed
      to correct the progressive bone disease in hemodialysis patients. We conclude
      that two-site ICMA for serum intact PTH which could be measured without
      radioisotopes nor scintillation counter is as useful as IRMA in hemodialysis
      patients.

PMID- 1395170
TI  - Decrease of tumor-like calcification in uremia despite aggravation of secondary
      hyperparathyroidism: a case report.
AB  - Extraskeletal pseudotumoral calcifications generally develop in uremic patients
      with a high calcium x phosphorus (Ca x P) product and severe secondary
      hyperparathyroidism. In the present case report we describe a chronic
      hemodialysis patient presenting with a massive calcification of the left shoulder
      region, severe aluminum (Al) intoxication and moderate hyperparathyroidism. Her
      initial serum Ca x P product was only slightly elevated: 5.01 mmol2/l2. Under
      deferoxamine treatment during the subsequent 4 months, Al overload decreased. On
      the other hand, parathyroid overfunction worsened, as reflected by an increase of
      the serum immunoreactive parathyroid hormone [1-84] level from initially 690 to
      1052 pg/ml (normal, 15-60 pg/ml) and an increase of alkaline phosphatase
      activity, and plasma calcitriol increased from undetectable to a low-normal
      value. Predialysis serum total Ca levels decreased rapidly from 2.9 to 2.5 mM but
      serum P concentrations remained elevated: 1.6-2.5 mM. Unexpectedly, the extent of
      the periarticular calcification diminished considerably during the same time
      period. The present observation shows that in a subset of uremic patients with Al
      overload, pseudotumoral calcifications may regress during Al chelation therapy
      despite progression of hyperparathyroidism. Since Al may predispose collagen to
      develop dystrophic or metastatic calcification, it is suggested that this process
      is reversible by correcting Al intoxication.

PMID- 1395171
TI  - Secondary hyperparathyroidism and sonographic evaluation of parathyroid gland
      hyperplasia in dialysis patients.
AB  - Ninety-six hemodialysis patients were examined by ultrasonography of the
      parathyroid glands to study the prevalence of parathyroid gland hyperplasia and
      to assess the relevance of sonography in the evaluation of secondary
      hyperparathyroidism. The results were compared with clinical, biochemical and
      radiological parameters. Thirty-two (33.3%) patients had sonographically enlarged
      glands. Of them 19 had 1 and 13 had 2 and more enlarged glands. Patients with
      enlarged glands, compared to those with undetected glands, had a significantly
      higher frequency of bone and joint pains (65.5% vs 40.6%), radiological features
      of hyperparathyroid bone disease (in hands 28.1% vs 6.9%, in acromioclavicular
      joints 37.5% vs 13.6%) and higher levels of intact serum parathyroid hormone (1
      84) concentration (52.8 +/- 47.9 pmol/l vs 18.1 +/- 18.0 pmol/l) and serum
      alkaline phosphatase concentration (260.2 +/- 201.1 U/l vs 129.8 +/- 127.3 U/l).
      Those with enlarged glands had been on dialysis for a longer period (87.7 +/-
      51.0 months vs 62.5 +/- 47.4 months). The severity of secondary
      hyperparathyroidism increased with the number of enlarged glands. Our study shows
      that ultrasonography is a useful noninvasive screening method for the evaluation
      of secondary hyperparathyroidism in patients on hemodialysis and that
      sonographically enlarged glands may be a measure of the severity of secondary
      hyperparathyroidism.

PMID- 1395172
TI  - Ionized calcium concentration in maintenance hemodialysis patients.
AB  - Since numerous formulae for "adjusted" total calcium and "calculated" ionized
      calcium are used in clinical practice, serum total and ionised calcium
      concentrations were measured in 20 hemodialysis patients with a wide range of
      serum total calcium and albumin concentrations. Patients were evaluated pre- and
      post-dialysis to document the effect of pH. Pre-dialysis total calcium varied
      from 1.70 to 3.17 mmol/L (mean 2.52 +/- 0.08) and a very close correlation
      between total and ionized calcium was found (r = 0.842; p less than 0.001) with
      50.2% being in the ionized form. Dialysis did not alter this relationship despite
      a significant increase in pH (0.09; p less than 0.01). A normal volunteer group
      also demonstrated a similar correlation between total and ionized calcium and
      while the non-ionized calcium concentration was positively and significantly
      correlated to the serum albumin concentration (r = 0.629; p less than 0.01) this
      was not the case in the dialysis patients, although the serum albumin range was
      much greater (18 to 46 g/L). These results suggest that the percentage of total
      calcium in the ionized form in dialysis patients is not different from the normal
      population and that minor changes in pH and albumin may not be as important as
      has previously been believed. While direct measurement is preferable, halving of
      the total calcium is a simple prediction of the ionized fraction.

PMID- 1395173
TI  - Minimal change nephrotic syndrome developed after non-surgical treatment of a
      thymoma.

PMID- 1395174
TI  - Renal cortical necrosis as complication of leprosy treatment.

PMID- 1395175
TI  - Rapidly progressive renal amyloidosis associated with uterine cervical cancer.

PMID- 1395177
TI  - Flavobacterium meningo-septicum septicemia and peritonitis complicating CAPD.

PMID- 1395176
TI  - Effect of recombinant human erythropoietin therapy on left ventricular
      hypertrophy in hemodialysis patients.

PMID- 1395178
TI  - Importance of nosocomial transmission of hepatitis C virus infection in dialysis
      units.

PMID- 1395180
TI  - Aspirin and elective surgical procedures.

PMID- 1395179
TI  - Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime
      performance.

PMID- 1395181
TI  - Ventricular arrhythmias and the autonomic tone in patients with mitral valve
      prolapse.
AB  - The aim of this study was to evaluate a possible relation between the autonomic
      tone determined by daily urine catecholamine excretion and the incidence of
      ventricular arrhythmias (VA) in patients with mitral valve prolapse (MVP). The
      study included 53 patients (31 women and 22 men) aged 19-52 years (mean age
      32.7). The diagnosis of MVP was based on medical history, physical examination,
      and echocardiography. Cardiac arrhythmias were detected by Holter monitoring and
      classified according to Lown grades. Daily heart rate and duration of corrected
      QT interval using Basett's formula were also analyzed. Daily urine adrenaline and
      noradrenaline levels were determined fluorometrically by Von Euler and Lishajko's
      method. The patients with Lown's grade III-V VA were evaluated with particular
      consideration. Student's t-test was used for statistical analysis. On Holter
      monitoring 26 patients showed VA, including 6 with grade I, 11 with grade II, 2
      with grade III, 4 with grade IV, and 3 with grade V according to Lown's
      classification. The remaining 27 patients were free of cardiac arrhythmias. Mean
      daily heart rate ranged from 54-93 beats/min (73 +/- 8.44, mean +/- SD) and
      corrected QT from 336-494 ms (411 +/- 37.17). Daily adrenaline and noradrenaline
      excretion for the whole group of patients were 0.01-16.2 micrograms (2.1 +/-
      2.38) and 1.6-31.0 micrograms (13.1 +/- 7.27), respectively, which was within
      normal range. However, the patients with serious ventricular arrhythmias showed
      significantly higher daily adrenaline excretion. Individual analysis of two
      thirds of patients with ventricular arrhythmias grade III-V showed daily urine
      noradrenaline levels exceeding mean values for the whole group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1395183
TI  - Is angiographic ventriculography necessary for the assessment of ischemic
      patients?
AB  - A total of 53 patients with a provisional diagnosis of ischemic heart disease and
      without any clinical evidence of valvular, congenital, or primary muscle heart
      disease were studied by echocardiography and biplane left ventricular
      cineangiography. For angiographic ejection fraction analysis, a program developed
      in our department for use on an Apple Macintosh computer interfaced to a
      digitizing tablet was employed. Echocardiographic outlines of systolic and
      diastolic images were traced with a digitizing system on the screen and ejection
      fractions were calculated by a program incorporated in the echo machine. Good
      echo windows allowing ejection fraction calculations were present in 35 patients.
      There was a good correlation between angiographic and echocardiographic ejection
      fraction (r = 0.7, SEE = 0.09), and wall motion assessment revealed no
      significant discrepancies between the two image modalities. The remaining 18
      patients had poor echo windows, preventing accurate echocardiographic
      determination of the ejection fraction. However, limited assessment of left
      ventricular size and wall motion was possible in all patients and allowed the
      identification of those who had impaired left ventricular function as judged by
      angiography (angiographic ejection fraction < 35%). We conclude that even in
      patients with poor echo windows echocardiographic assessment of left ventricular
      function provides clinical information similar to angiography which should not be
      considered mandatory for the investigation of ordinary ischemic patients.

PMID- 1395182
TI  - Influence of serum potassium on the electrocardiographic pattern of left
      ventricular hypertrophy in primary hyperaldosteronism.
AB  - Only a few studies deal with electrocardiographic (ECG) signs of left ventricular
      hypertrophy (LVH) in patients with primary hyperaldosteronism, although it may be
      presumed that many factors such as arterial hypertension, hypokalemia, increased
      blood volume, and decreased activity of the renin-angiotensin system can modify
      LVH pattern in this entity. For that reason, we evaluated ECG signs of LVH in 55
      patients with primary hyperaldosteronism hospitalized in our department from 1971
      to 1990. These data were compared with age, serum potassium level, plasma renin
      activity (PRA) and-in 14 patients-with left ventricular mass, measured
      echocardiographically. We found inverse correlation between serum potassium
      concentration and the Sokolow-Lyon index: SV1 + RV5/6 (r = -0.47, p < 0.001).
      Among 24 patients with only abnormal QRS voltage, without ST-T changes suggestive
      of LVH, 19 (79.2%) had hypokalemia. In multivariate analysis, potassium
      concentration was the single independent predictor of an abnormal QRS voltage: 
      0.743, p = 0.01 vs. 0.153 (age), -0.337 (PRA) and 0.454 (LV mass). Our
      observations suggest that hypokalemia is an important factor influencing an
      amplitude of QRS complexes and may be responsible for false-positive LVH
      diagnosis.

PMID- 1395184
TI  - QT-interval abnormalities in hypertrophic cardiomyopathy.
AB  - To examine whether QTc and QTc dispersion across the leads of a surface
      electrocardiogram (ECG) are different in patients with hypertrophic
      cardiomyopathy (HCM) compared with normal subjects, we measured QT and calculated
      QTc in all 12 leads of a surface ECG in 24 patients with HCM and in 20 age- and
      sex-matched normal control subjects. Maximal QTc was prolonged in HCM patients
      (465 +/- 24 ms) compared with controls (410 +/- 20 ms) (p < 0.001). QTc
      dispersion defined as the difference of maximum-minimum QTc was also greater in
      HCM patients (71 +/- 21 ms) compared with normals (35 +/- 11 ms) (p < 0.001). A
      correlation was found between the degree of left ventricular hypertrophy
      expressed by the maximal wall thickness and maximal QTc (r = 0.48, p < 0.02).
      However, QTc dispersion did not correlate with maximal wall thickness. Thus,
      patients with HCM show a prolonged QTc (> 440 ms) and increased QTc dispersion
      compared with normal subjects. In addition, the degree of left ventricular
      hypertrophy correlates with maximal QTc. The presence of a prolonged QT with
      increased regional dispersion may be associated with the occurrence of serious
      ventricular arrhythmia and sudden death in HCM.

PMID- 1395185
TI  - Progression of valvular sclerosis in end-stage renal disease treated by long-term
      peritoneal dialysis.
AB  - While patients with end-stage renal disease treated by intermittent hemodialysis
      have frequent and progressive valve disease, nothing is known of the prevalence
      and course of valvular abnormalities in patients treated with continuous
      ambulatory peritoneal dialysis (CAPD). Therefore, valves of 24 CAPD patients
      (ages 55 +/- 11 years; CAPD duration: 29 +/- 28 months) were studied in a
      prospective echocardiographic and Doppler echocardiographic follow-up analysis
      over 35 months. Most frequent findings were sclerosis of the aortic annulus (100%
      at both assessments) and of the anterior mitral valve leaflet (first vs. follow
      up assessment: 88 vs. 96%). Sclerosis of the mitral valve annulus (58% vs. 63%),
      right coronary (54 vs. 63%) and noncoronary (50 vs. 67%) cuspis of the aortic
      valve and of the posterior mitral valve leaflet (25 vs. 50%) were less frequent
      but tended to be progressive (p = NS). The moderate form of mitral and aortic
      valve sclerosis was more frequent than the severe form (p < 0.01 each) at both
      assessments. Patients with progressive valve disease were older (60 +/- 9 vs. 50
      +/- 11 years; p < 0.025) and had a higher frequency angina pectoris than those
      without a progression (5 vs. 0 patients; p < 0.05). The number of patients with
      regular sinus rhythm decreased (from 22 to 16; p < 0.03), atrial fibrillation
      developed in four patients, atrioventricular node rhythm following
      atrioventricular conduction defect developed in one patient, and atrioventricular
      conduction defect required implantation of a pacemaker in one patient.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1395186
TI  - Single moving dipole obtained from magnetic field of the heart in patients with
      left ventricular hypertrophy.
AB  - Magnetocardiograms (MCGs) were recorded by means of a second-derivative SQUID
      (superconducting quantum interference device) magnetometer in 20 normal subjects
      and 28 patients with left ventricular overload to analyze the activation sequence
      of the heart and amplitude of estimated current source. In the normal subjects,
      the dipole was directed to the left and gradually superiorly 40 ms after the
      beginning of the QRS wave mainly due to the activation of the left ventricle. In
      the patients with hypertension, the direction and location of the dipoles were
      similar to those of the normal subjects, but their dipole moments were increased.
      In the patients with mitral regurgitation, the dipoles of late QRS were directed
      more inferiorly than in the normal subjects and their amplitude was increased. In
      the patients with aortic valve disease, the amplitude of the dipoles was
      increased markedly and their location was deviated more to the left than the
      dipoles of the normal subjects. We established the criterion for diagnosis of LVO
      from the dipole moment of 50 ms of 3.13 x 10(-3) A or more. The sensitivity of
      this criterion is significantly higher in the diagnosis of left ventricular
      overload than the electrocardiogram (ECG). The present study shows that the
      moving dipole method is useful to determine the increased electromotive force in
      patients with left ventricular overload and that sensitivity in diagnosis of left
      ventricular overload is increased.

PMID- 1395187
TI  - Cardiac pathology in 2007 consecutive forensic autopsies.
AB  - The incidence of various types of cardiovascular disease was evaluated in 2007
      consecutive forensic patients. Cardiovascular deaths accounted for 22.8% of the
      study patients and atherosclerotic coronary heart disease was the most common
      type of cardiac disease (18%). Among subjects dying of atherosclerotic coronary
      disease, sudden death was three times more frequent than acute myocardial
      infarction. Expected cardiac findings included the incidence of severe coronary
      atherosclerosis (21%), floppy mitral valves (5%), and congenital bicuspid aortic
      valves (1%). Major cardiac findings occurred in 32% and minor cardiac findings
      were found in 40%. Only 17% of hearts were anatomically normal. An unexpected
      cardiac necropsy finding included the high frequency of myocardial bridges (23%).
      Unexpected cardiac findings included the low incidence of acute myocarditis
      (0.6%) and common finding of tunneled epicardial coronary arteries ("myocardial
      bridges") (23%).

PMID- 1395188
TI  - Cardiac tamponade in a patient with Gaucher's disease.
AB  - Gaucher's disease, a familial inborn error of metabolism associated with
      hepatosplenomegaly and hypersplenism, was first described by Earnest Gaucher in
      1882. By 1959, Hsia found published reports on more than 300 cases. Most reports
      mentioned the bleeding tendencies of patients with Gaucher's, but show that major
      hemorrhagic complications are rare. We report a case of hemorrhagic pericarditis
      with cardiac tamponade in a patient with Type I Gaucher's disease.

PMID- 1395189
TI  - Torsade de pointes complicating acute myocardial infarction: the importance of
      autonomic dysfunction as assessed by heart rate variability.
AB  - Torsade de pointes is a polymorphic ventricular tachycardia associated with QT
      interval prolongation rarely reported to occur in the setting of an acute
      myocardial infarction. Autonomic dysfunction has been implicated as a major
      stimulus for the development of this dysrhythmia. We describe the case of an 80
      year-old woman who presented with an acute myocardial infarction and progressive
      QT-interval lengthening. An 89-beat run of torsade de pointes occurred during the
      time of the peak creatine phosphokinase (CPK) without electrolyte abnormalities
      or antiarrhythmic therapy. Assessment of autonomic tone using power spectral
      analysis of two consecutive 24-h Holter recordings was performed indicating that
      a transient decrease in heart rate variability and increase in sympathetic tone
      preceded the tachyarrhythmia. This case shows the potential usefulness of heart
      rate variability analysis as a marker for autonomic dysfunction and
      arrhythmogenesis, particularly during myocardial ischemia.

PMID- 1395190
TI  - Diagnosis of aortic pseudoaneurysm by echocardiography.
AB  - The diagnosis of pseudoaneurysm of the ascending aorta is of paramount importance
      because of its propensity to rupture. As the frequency of surgical procedures
      involving the aortic root and valve increases, an increase in the incidence of
      aortic pseudoaneurysm may be anticipated. We recently studied a patient who
      developed pseudoaneurysm of the ascending aorta following repair of a Type I
      aortic dissection, utilizing a composite graft. Two-dimensional echocardiography
      with color flow and pulsed Doppler imaging showed a large perigraft cavity
      communicating with the aorta. Echocardiography provides a safe noninvasive
      diagnostic tool for the evaluation of the aorta postoperatively and for screening
      for pseudoaneurysm formation in the follow-up period.

PMID- 1395191
TI  - Delayed presentation of a mitral annular perforation complicating Staphylococcus
      aureus infective endocarditis.
AB  - This report describes a patient who presented with congestive heart failure
      secondary to a mitral annular-left atrial fistula. There was a remote history of
      Staphylococcus aureus endocarditis involving the mitral valve which was treated
      medically 30 years previously. The sterile fistula was managed surgically with an
      annuloplasty.

PMID- 1395192
TI  - Recurrent myocardial infarction in a postpartum patient receiving bromocriptine.
AB  - Myocardial infarction in puerperium is infrequently reported. Spasm, coronary
      dissection, or atheromatous etiology has been described. Bromocriptine has been
      implicated in several previous case reports of myocardial infarction in the
      puerperium. Our case (including an inadvertent rechallenge) suggests such a
      relationship. Although generally regarded as "safe," possible serious cardiac
      effects of bromocriptine should be acknowledged.

PMID- 1395193
TI  - Willem Einthoven--the father of electrocardiography.

PMID- 1395194
TI  - Serial chest thumps for the treatment of ventricular tachycardia in patients with
      coronary artery disease.

PMID- 1395195
TI  - Is menstruation a contraindication to thrombolytic therapy?

PMID- 1395196
TI  - Aging in the Americas: its impact on cardiovascular health.

PMID- 1395197
TI  - The prevention of atherosclerosis with antioxidants.
AB  - Recent research findings have suggested a role for pharmacologic as well as
      nutritional antioxidants in the prevention of atherosclerosis. Data from animal
      studies as well as cell culture experiments have shown that the drug probucol,
      which has hypocholesterolemic and antioxidant properties, is able to prevent
      oxidative modification of low density lipoproteins (LDL). Such modification is
      now believed to play a major part in the initiation and progression of arterial
      lesions. Nutrients with antioxidant properties such as vitamins C and E, beta
      carotene, and mono-unsaturated fatty acids (when they replace polyunsaturated
      fatty acids) can reduce the susceptibility of LDL to oxidation. Antioxidant
      therapy, if proven useful, should be considered an adjunct to lipid-lowering
      therapy in order to have the greatest impact on coronary heart disease.

PMID- 1395198
TI  - Comparison of exercise electrocardiography and dobutamine echocardiography.
AB  - It is uncertain whether dobutamine echocardiography is a better test than
      exercise electrocardiography for the detection of coronary disease in patients
      who can exercise. We compared the hemodynamics, sensitivity, and specificity of
      these tests in 24 patients, 16 with coronary disease and 8 controls. The tests
      were performed within six weeks of one another and were interpreted without
      knowledge of other clinical data. The exercise electrocardiogram was considered
      abnormal if the patient developed one mm of ST-segment depression, while the
      dobutamine test (up to 40 micrograms/kg/min) was considered abnormal if the
      patient developed ST-segment depression or a left ventricular wall motion
      abnormality. Exercise testing resulted in a higher heart rate (145 +/- 29 vs. 110
      +/- 24, p less than 0.001) and blood pressure (176 +/- 31 vs. 148 +/- 24, p less
      than 0.001). Dobutamine testing was 25% more sensitive than exercise testing (94
      vs. 69%, 95% confidence interval for difference is 0 to 50%, p = 0.09), while
      exercise testing was 38% more specific (88 vs. 50%, 95% confidence interval for
      difference is -3 to 79%, p = 0.14). We conclude that exercise results in a higher
      heart rate and blood pressure than dobutamine infusion. Differences in
      sensitivity and specificity are inconclusive, but indicate that the sensitivity
      of exercise testing is, at best, equivalent to dobutamine testing, while any
      increase in specificity with dobutamine testing, compared with exercise testing,
      would not be clinically significant.

PMID- 1395199
TI  - A "lipo-protective" effect of a fixed combination of captopril and
      hydrochlorothiazide in antihypertensive therapy.
AB  - Increases of triglycerides and total cholesterol have been reported during
      treatment with antihypertensive drugs, most notably with beta blockers and
      diuretics. ACE inhibitors, on the other hand, are not known for having a negative
      effect on lipid profile. To evaluate the effects of a fixed combination of
      captopril and hydrochlorothiazide on lipid metabolism, blood pressure, and
      quality of life, we performed an open prospective study. A total of 2,154
      patients with or without hypercholesterolemia, but not receiving lipid lowering
      drugs, were enrolled. Of the 1891 evaluable patients at baseline, 34.1% had a
      moderate risk with total cholesterol between 5.2 and 6.5 mmol/l (mean 5.8 mmol/l)
      and 41.3% had a high coronary heart disease (CHD) risk with total cholesterol
      higher than 6.5 mmol/l (mean 7.3 mmol/l). After six months of treatment, the
      median cholesterol level in the moderate risk group decreased from 5.8 to 5.4
      mmol/l (p less than 0.0003) and in the high risk group from 7.3 to 6.3 mmol/l (p
      less than 0.0001). Triglycerides also decreased, whereas high density lipoprotein
      (HDL) increased in both risk groups. Systolic and diastolic blood pressure fell
      as expected and quality of life improved. The fixed combination was well
      tolerated. We observed a significant improvement of lipid profile in patients
      with mild to moderate hypertension while undergoing treatment with the fixed
      combination of captopril and hydrochlorothiazide. We suggest that captopril may
      balance the negative effects of hydrochlorothiazide on lipid metabolism in
      patients with hypertension and concomitant hyperlipidemia.

PMID- 1395200
TI  - Noninvasive evaluation of left ventricular performance by the shortest distance
      between mitral leaflets coaptation and interventricular septum at end-systole.
AB  - We attempted to evaluate left ventricular performance from the shortest distance
      between the mitral leaflets coaptation and the interventricular septum at end
      systole (MVC-IVS distance). The subjects were 37 patients with coronary artery
      disease (CAD) with prior myocardial infarction (MI), 8 with CAD without prior MI,
      22 with atypical chest pain, and 4 with aortic regurgitation. The MVC-IVS
      distance was measured on a two-dimensional echocardiogram obtained from the
      parasternal or apical long-axis view and frozen at end-systole. Left ventricular
      end-systolic volume and end-diastolic volume were obtained by left
      ventriculography, and the left ventricular ejection fraction was calculated. A
      significant positive correlation was observed between the MVC-IVS distance and
      the end-systolic volume (r = 0.83, p less than 0.001); a close correlation was
      observed between the MVC-IVS distance end-systolic volume and ejection fraction
      by monoexponential fitting (r = -0.91, p less than 0.001). Thus, a significant
      negative correlation was observed between the MVC-IVS distance and the left
      ventricular ejection fraction (LVEF) (r = -0.83, p less than 0.001). An MVC-IVS
      distance of greater than or equal to 30 mm suggests diagnosis of left ventricular
      dysfunction (LVEF less than 50%) with high sensitivity (94.4%) and specificity
      (90.6%), while a value less than 30 mm suggests that the left ventricular
      performance is likely to be normal. Thus one can easily evaluate the left
      ventricular performance noninvasively using this new index.

PMID- 1395201
TI  - Myocardial alterations induced by prolonged noradrenaline administration in
      various doses.
AB  - Prolonged noradrenaline administration to rats in steadily increasing dosages for
      a period of one to four weeks (cumulative doses 25-35 mg/kg) resulted in the
      development of focal necrotic areas with abundant collagen fibers and marked
      hypertrophy of cardiomyocytes. Cellular diameter was higher by 37-44% and
      extracellular space area by 70-100%. A combination of overcontracted and
      overdistended sarcomeres in some cardiomyocytes and a twofold rise in serum
      creatine kinase presumably reflected cellular calcium overload. Myocardial high
      energy phosphate content was depleted to 50-62% of the control level. The extent
      of this depletion positively correlated with a decrease in heart rate and cardiac
      output of the isolated heart. The latter may be attributed to limited left
      ventricular filling caused by elevated LV diastolic pressure and stiffness.
      Minimal metabolic and functional changes were observed after lowest noradrenaline
      dose (5 mg/kg for nine days) that was followed by only moderate depletion of
      myocardial phosphocreatine content and moderate rise in LV diastolic stiffness.
      Results suggest that energy-deficient increase in myofibrillar stiffness may form
      the basis for decreased myocardial distensibility and cardiac pump failure.

PMID- 1395202
TI  - Electrophysiologic studies in atrial flutter.
AB  - The clinical electrophysiologic approaches to atrial flutter (F) have been
      activation mapping and the observation of changes induced by programmed
      stimulation. Sequential endocardial activation mapping has recently yielded
      information indicating that common F is produced by a large right atrial (RA)
      reentry circuit, with counterclockwise rotation in the frontal plane, including
      the inferior vena cava in its center. Functional block in the crista terminalis
      and conduction slowing in the approaches to the atrioventricular node seem to be
      important to support reentry. F inscribing positive deflections in the inferior
      leads usually follows the same path, but in a clockwise direction. Atypical F may
      be produced by left atrial circuits. Atrial stimulation during F entrains the
      circuit, resetting it with each stimulus. Collision between antidromic and
      orthodromic activation during entrainment produces fusion that can be identified
      in the surface electrocardiogram. The last paced activation restarts F, unless
      circuit penetration has been enough to modify it by block or disorganization.
      Entrainment may result in F acceleration, with changes in activation sequence,
      suggesting a different type of reentry, possibly based on functional factors.

PMID- 1395204
TI  - Triggered activity as arrhythmogenic mechanism after myocardial infarction:
      clinical and electrophysiologic study of one case.
AB  - In a woman with an old infarction and sustained ventricular tachycardia,
      tachycardias were only inducible after short-long RR sequences. After
      isoprenaline, tachycardias became incessant and all were preceded by short-long
      RR sequences. This strongly suggests that triggered activity plays a role in
      initiation of ventricular tachycardias in postinfarction patients.

PMID- 1395203
TI  - Anatomy, histology, and pathology of coronary arteries: a review relevant to new
      interventional and imaging techniques--Part IV.
AB  - In the last 15 years, intense interest has focused on various interventional
      pharmacologic and mechanical forms of therapy for the treatment of
      atherosclerosis coronary artery disease. Many techniques and devices (dilating
      balloons, perfusion catheters, thermal probes and balloons, lasers, atherectomy
      devices, stents, intravascular ultrasound) have been used or are under study for
      future use. Many of these techniques and devices require an understanding of
      histologic and pathologic features of the coronary arteries and diseases which
      affect them. This article reviews selective areas of anatomy, histology, and
      pathology relevant to the use of various new interventional techniques. Part IV
      of this review will focus on congenital coronary artery anomalies, myocardial
      bridges, coronary aneurysm, emboli, and dissection and clinical implications
      regarding echocardiographic imaging techniques.

PMID- 1395205
TI  - His bundle ablation for supraventricular arrhythmias to avoid spurious shocks of
      an implanted defibrillator.
AB  - Atrial fibrillation with fast ventricular response remains a matter of concern in
      patients treated with an implantable cardioverter defibrillator (ICD). A patient
      with dilated cardiomyopathy, suffering from atrial arrhythmias and recurrent
      cardiac arrest due to both ventricular tachycardia and ventricular fibrillation,
      is presented. Ablation of the AV node by means of low-energy direct-current
      shocks with subsequent pacemaker implantation was performed before ICD
      implantation. The patient received shocks after four months, when he had
      recurrence of AV conduction with a slow ventricular rate. Pacemaker interaction
      was excluded, and no short ventricular arrhythmias were observed. During
      electrophysiologic study after electrical conversion of atrial fibrillation,
      persistent second degree heart block was documented, giving further evidence that
      atrial arrhythmias were not responsible for the shocks. The patient's functional
      status remains good after more than 18 months of follow-up.

PMID- 1395206
TI  - Splenic infarction: a complication of cardiac catheterization.
AB  - Patients with extensive atherosclerosis are at increased risk of developing
      embolic complications during cardiac catheterization. We describe a 51-year-old
      man with unstable angina and bilateral leg claudication who developed fever and
      right upper abdominal pain shortly after cardiac catheterization. Liver-spleen
      scintigraphy demonstrated a wedge-shaped filling defect compatible with splenic
      infarction, and serial scans performed over a period of five months showed
      resolution of this finding. Splenic infarction tends to be under-diagnosed, and
      physicians should be aware of this potentially serious complication of cardiac
      catheterization.

PMID- 1395207
TI  - A case of accessory mitral valve leaflet associated with solitary mitral cleft.
AB  - Accessory mitral valve leaflet is a rare congenital anomaly. More than half of
      the cases show other congenital cardiac defects and almost all of the cases show
      subaortic obstruction. We report a case of an accessory mitral valve tissue
      without outflow obstruction associated with mitral cleft of the posterior mitral
      leaflet. To our knowledge, this is the first reported case of the combination of
      these two congenital anomalies.

PMID- 1395208
TI  - Robert Ritchie Linton.

PMID- 1395209
TI  - Relationship between the extent of coronary artery disease and indicators of free
      radical activity.

PMID- 1395210
TI  - Clinical significance and management of arrhythmias in the heart failure patient.
AB  - Congestive heart failure (CHF) is a common manifestation of hypertension,
      coronary artery disease, and dilated cardiomyopathy. The Framingham study showed
      that the incidence of CHF increases twofold with each decade of age. The presence
      of CHF increases the age-adjusted death rate 5.5-fold for women and 8-fold for
      men, and it increases the sudden death rate 5.5-fold in both men and women.
      Ventricular arrhythmias are a common accompaniment of CHF. Ambient ventricular
      premature complexes occur in most of these patients, and nearly one half of all
      CHF patients will have nonsustained ventricular tachycardia on a 24-h ambulatory
      electrocardiographic (Holter) recording. In addition, low left ventricular
      ejection fraction (LVEF) predicts inducible sustained ventricular tachycardia on
      electrophysiologic study. One-year mortality increases with worsening New York
      Heart Association (NYHA) Functional Class and decreasing LVEF. As the overall
      yearly mortality increases, the proportion of patients who die of arrhythmias
      decreases. The precise mechanism of death is frequently difficult to assess.
      Nonarrhythmic causes of death include CHF, shock, electromechanical dissociation,
      and myocardial rupture. Arrhythmic causes are most commonly due to ventricular
      tachycardia/ventricular fibrillation. Bradycardic events (asystole or heart
      block) are usually associated with progressively worsening CHF. Noncardiac causes
      that may confuse classification include pulmonary embolus and cerebrovascular
      accident. Because many patients have ischemic heart disease as the etiology of
      the CHF, a recurrent ischemic event can likewise make classification difficult.
      Overall, approximately one half of all deaths in CHF are arrhythmic and one half
      are nonarrhythmic.

PMID- 1395211
TI  - Congestive heart failure: new therapeutic strategies.
AB  - Angiotensin converting enzyme inhibitors (ACE-I) are widely used in patients with
      severe heart failure on the basis of the significant improvement in mortality in
      the CONSENSUS-I trial in patients with Class IV heart failure. Recent data from
      the 5-year clinical trial Studies of Left Ventricular Dysfunction (SOLVD) suggest
      a role for ACE-I in patients with mild to moderate heart failure as well as in
      those with asymptomatic left ventricular dysfunction. The SOLVD treatment trial
      in patients with a left ventricular ejection fraction (LVEF) less than or equal
      to 35% and treated for heart failure with conventional therapy including
      digitalis, diuretics, or vasodilators demonstrated that the addition of enalapril
      resulted in a significant reduction in mortality from heart failure as well as in
      the combined end point of death plus hospitalization from heart failure. These
      data suggest that ACE-I should be the base of therapy for patients with mild to
      moderate heart failure, as well as for those with severe heart failure.

PMID- 1395212
TI  - Management of heart failure in valve regurgitation.
AB  - Heart failure from valve regurgitation usually results from aortic and/or mitral
      valve dysfunction. Heart failure resulting from acute and chronic valve
      regurgitation should be considered separately.

PMID- 1395213
TI  - Management of the patient awaiting cardiac transplantation.
AB  - The spectacular clinical success of heart transplantation (HTTX) in the
      cyclosporine era has engendered challenging new clinical problems that include
      long-term management of patients with severely compromised systolic function,
      preparation of potential HTTX recipients for major surgery followed by
      immunosuppression, and ethical and rational distribution of limited numbers of
      donated organs. The magnitude of these challenges may seem overwhelming.
      Fortunately, clinicians have the luxury of dealing with the issues involved one
      patient, and one step, at a time. The continued efforts of clinical investigators
      have clarified important management principles. There is a growing appreciation
      of the pivotal importance of mitral valve function in determining the response to
      medical therapy and long-term prognosis in this patient population. Enthusiasm
      for pharmacologic control of asymptomatic ventricular ectopy has waned; instead,
      the restoration and maintenance of normal atrial function has clearly taken
      precedence. In preparation for surgery, new endoscopic techniques offer great
      advantages. The use of high-technology support devices as "bridges to
      transplantation" has been re-examined in view of the relatively poorer short- and
      long-term prognosis of patients managed with these devices. Increasingly, the
      optimal scenario for HTTX entails transplantation of a severely compromised but
      medically stable patient. As specific therapy, HTTX today has relatively limited
      application to the vast majority of patients with heart failure (HF). Seventeen
      hundred heart transplants will do little to directly affect the 400,000 patients
      in the United States who each year develop symptomatic HF.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1395214
TI  - Strategies to manage the heart failure patient after transplantation.
AB  - Cardiac transplantation has emerged as an effective form of therapy for end-stage
      congestive heart failure (CHF), but patients are predisposed to both dilated and
      restrictive congestive physiology. The etiologies of post-transplant CHF are
      unique and complicated, most certainly reflecting a chronic rejection process
      that has yet to be elucidated. Successful identification of underlying
      pathophysiologic mechanisms and subsequent therapeutic approaches will require
      close coordination among cardiologists, cardiac surgeons, and immunobiologists.

PMID- 1395216
TI  - Anti-CD4 antibodies in rheumatoid arthritis.

PMID- 1395215
TI  - Pathophysiology of congestive heart failure.
AB  - Congestive heart failure is a syndrome common in the United States, especially in
      elderly patients. The most common etiology is coronary artery disease. A number
      of general factors contribute to the heart failure syndrome, including loss of
      muscle, decreased myocardial contractility, pressure or volume overload, or
      restricted filling. All of these factors may play a role in a given patient as,
      for example, with coronary artery disease. Although systolic dysfunction with a
      reduced ejection fraction is the most common heart failure syndrome, up to 40% of
      patients may have a relatively preserved ejection fraction with diastolic
      dysfunction. As the heart begins to fail, a number of compensatory mechanisms are
      activated. These include increased heart rate, the Frank-Starling mechanism,
      increased catecholamines, activation of the renin-angiotensin system, and release
      of atrial natriuretic peptides. Although these mechanisms are initially helpful
      to the cardiovascular system, they frequently overshoot, initiating a vicious
      cycle. For example, with a decrease in cardiac output, there is a reflex increase
      in systemic vascular resistance in order to maintain perfusion pressure. This
      increase in resistance, however, acts as a load on the left ventricle and further
      reduces cardiac output. The best evidence for the existence of this vicious cycle
      is the beneficial change in hemodynamics produced by vasodilator drugs and the
      ACE inhibitors. Thus, an understanding of pathophysiology allows for the
      selection of rational therapy. An unresolved problem in heart failure patients is
      how best to reduce the high incidence of sudden death, which is one of the major
      challenges for the future.

PMID- 1395217
TI  - Tiopronine-induced reduction of rheumatoid factor functional affinity and
      asialylated IgG in patients with rheumatoid arthritis.
AB  - Serum and synovial fluid (SF) from 16 rheumatoid arthritis patients were
      evaluated before and after a 2-month treatment with tiopronine (TP). The levels
      of rheumatoid factor (RF) declined, as did the functional affinity of the
      remaining RF (p less than 0.01 in serum and p less than 0.05 in SF). Concomitant
      restoration of the sialylation of IgG was observed (p less than 0.05 in serum and
      SF). Following an initial increase, a significant reduction was observed in the
      level of soluble interleukin-2 receptors in serum (p less than 0.05) and SF (p
      less than 0.05) after treatment with TP.

PMID- 1395218
TI  - Sjogren's syndrome and mixed connective tissue disease.
AB  - We investigated the clinical significance of the close association of Sjogren's
      syndrome (SS) with mixed connective tissue disease (MCTD) by analyzing the
      clinical manifestations, sialographic findings and immunological parameters of
      MCTD and primary SS. The prevalence of sialectasia or SS in MCTD was
      significantly higher than in any other connective tissue diseases. The prevalence
      of Raynaud's phenomenon, swollen fingers, arthralgias, lymphadenopathy,
      sclerodactyly, muscle weakness, fever and erythema was significantly higher in
      MCTD than in primary SS. There were no significant differences between these
      manifestations in MCTD patients with sialectasia or SS, and those in MCTD
      patients without sialectasia or SS. Although the levels or prevalence of the
      erythrocyte sedimentation rate, CRP, antinuclear factor, anti-DNA antibody and
      anti-RNP antibody were significantly greater in MCTD than in primary SS, there
      were no significant differences in the levels or the prevalence of laboratory
      abnormalities between MCTD with sialectasia or SS, and MCTD without sialectasia
      or SS. Moreover, there was a strict dissociation between the occurrence of anti
      RNP antibody and anti-SS-B antibody both in MCTD and primary SS. These results
      suggest that the association of secondary SS or sialectasia in MCTD, although
      more common than in other connective tissue diseases, is merely a consequence of
      MCTD and does not influence the clinical course of MCTD.

PMID- 1395219
TI  - The effects of 20 weeks of physical fitness training in female patients with
      fibromyalgia.
AB  - During a period of 20 weeks 18 female patients with fibromyalgia participated in
      a 60-minute exercise program twice a week. A control group, comprising 17
      patients, was told not to change their physical activity level. Eleven patients
      in the training group and fourteen in the control group completed the study. The
      results at entry were compared to those after 20 weeks, as well as being compared
      to the results of the control group. No statistically significant changes or
      differences in general pain, pain coping and fatigue were seen after 20 weeks.
      Improved dynamic endurance work performance for the upper extremity was found,
      however, in the training group, measured as the strength of the first (p = 0.01)
      and the last repetition (p = 0.003). These results differed from the results of
      the control group (p = 0.02 and p = 0.003). It is concluded that fibromyalgia
      patients may undergo low-intensity dynamic endurance training without
      experiencing exacerbation of their general pain and fatigue symptoms.

PMID- 1395220
TI  - Salivary gland echography in primary and secondary Sjogren's syndrome.
AB  - A series of different ultrasonographic abnormalities detected by salivary gland
      echography (SGE) were investigated for their discriminant power for Sjogren's
      syndrome (SS) in 53 patients with either primary SS (n = 27) or secondary SS (n =
      26), as well as in 90 controls. Among the controls, 26 suffered from dry mouth
      and/or recurrent or persistent swelling of at least one parotid or submandibular
      gland due to other selected disorders, while 64 were healthy, asymptomatic
      subjects. Mild, evident or gross inhomogeneous parenchymal patterns were the only
      variables selected by stepwise discriminant analysis, when comparing patients to
      controls. However, a mild submandibular inhomogeneity did not prove useful for
      such a discrimination. Based on these data, a simplified evaluation and
      standardised quantification of salivary involvement, as detected by SGE, is
      proposed using an echographic score (range 0 to 6) which assigns points to the
      different degrees of glandular inhomogeneity. Score values above 0 showed a
      sensitivity of 88.8% in primary SS and of 53.8% in secondary SS, as well as a
      specificity of 84.6% and of 92.2% with respect to either symptomatic or healthy
      controls. The lower sensitivity of SGE for patients with secondary SS presumably
      was a result of their milder salivary involvement.

PMID- 1395221
TI  - Synovial extracellular matrix II. Specific incorporation of immunoglobulin into
      the cell-free matrix of pannus.
AB  - To determine whether immune complex-like material is incorporated into the
      extracellular matrix (ECM) of proliferated RA synovium, cell-free matrices were
      isolated from pannus removed at joint replacement surgery, and were subjected to
      differential extraction. When the IgG and albumin concentrations in the ECM
      extracts were compared to those in simultaneously obtained synovial fluids, the
      IgG was found to be enriched 8.8-fold. Approximately 95% of the IgG was
      extractable with 6M Guanidine-HCl and 8 M Urea-B-ME. Further extraction with
      collagenase and low-pH buffers did not result in any additional recovery of IgG.
      Matrix-associated IgG demonstrated a restricted mobility on IEF with a pI of 4.8.
      The extracellular matrix of RA pannus is enriched in an acidic IgG species.
      Incorporation of IgG appears to be secondary to non-covalent interactions and may
      represent an additional reservoir of immune complex material in the rheumatoid
      joint.

PMID- 1395223
TI  - Successful treatment of psychosis secondary to SLE with high dose intravenous
      immunoglobulin.
AB  - A 23-year-old woman with SLE was admitted because of severe psychosis manifested
      by depression, delusions and the inability to perform minimal daily activities.
      The patient refused treatment with steroids, but was later convinced to try
      treatment with intravenous immunoglobulin (IVIG). Following treatment with IVIG a
      marked improvement was noted in her mental status and she was discharged. During
      a follow-up period of 18 months she resumed normal life; she does not receive any
      drugs currently and no psychiatric abnormalities have been noted. It is suggested
      that IVIG may be considered in the treatment of lupus cerebritis, especially when
      serious complications develop and other treatment modalities are ineffective.

PMID- 1395222
TI  - Molecular detection of persistent Borrelia burgdorferi in a man with
      dermatomyositis.
AB  - A 40-year-old white man with a several year history of various immunologic
      disorders, including anti-Jo-1 autoantibody positive dermatomyositis, developed
      clinical Lyme disease after being biten by a tick. The patient was treated with
      oral tetracycline and his initial symptoms resolved; however, he suffered an
      exacerbation of his muscle disease which was difficult to control despite
      cytotoxic therapy. Antibiotic therapy was reinstituted after Borrelia burgdorferi
      was detected in the patient's peripheral blood leukocytes by the polymerase chain
      reaction (PCR). All serologic, T-cell stimulation, and western blot analyses,
      however, were negative. The patient's disease responded to oral ampicillin,
      probenecid therapy and concurrent cytotoxic therapy. Subsequent leukocyte PCR
      testing has been negative for the causative agent of Lyme disease. This case may
      provide an example of the in vivo immuno-modulatory effects of spirochetes in
      human autoimmune disease. In addition, this case emphasizes the potential
      clinical utility of PCR technology in evaluating the persistent sero-negative
      Lyme disease which may occur in immunocompromised individuals.

PMID- 1395224
TI  - Reflex sympathetic dystrophy syndrome: a review.
AB  - Reflex sympathetic dystrophy syndrome is a serious and potentially disabling
      condition. Early diagnosis and treatment are essential to control the disorder
      and restore the patient's quality of life. The cardinal clinical features,
      radiological changes, etiopathologic advances, and current approaches to proper
      diagnosis and treatment will be discussed.

PMID- 1395225
TI  - Spondyloepiphyseal dysplasia tarda simulating juvenile arthritis: clinical and
      molecular genetic observations.
AB  - A sibship is reported in which two of three children developed a symmetrical
      polyarthropathy associated with a mild spondyloepiphyseal dysplasia. Although the
      physical findings resembled juvenile arthritis, laboratory investigations for
      inflammatory disease were entirely negative. Molecular studies in members of this
      family showed that none of them had any structural rearrangements or other major
      abnormality of the type II procollagen gene (COL2A1). The laboratory findings in
      this family with "pseudo-rheumatoid arthritis" do not exclude the possibility of
      a minor mutation of the type II procollagen gene or a defect in the processing of
      articular cartilage collagens.

PMID- 1395226
TI  - Muscle strength and endurance compared to aerobic capacity in primary
      fibromyalgia syndrome.

PMID- 1395227
TI  - Cytarabine therapy for rheumatoid arthritis.

PMID- 1395228
TI  - Baker's cyst infected by Candida albicans.

PMID- 1395229
TI  - Polymyositis associated with chronic lymphocytic leukemia: a new case.

PMID- 1395230
TI  - Alpha interferon in the treatment of mixed cryoglobulinaemia associated with
      hepatitis C virus infection.

PMID- 1395231
TI  - Chlamydia-induced arthritis. Immunofluorescent antibody studies of the synovial
      fluid from 4 patients.

PMID- 1395232
TI  - Scintimetric study of the bone response around noncemented knee prosthesis.
      Preliminary results.
AB  - The bone response to a noncemented knee prosthesis was observed by quantified
      isotopic gammagraphy. One hundred six sequential scintimetric explorations were
      performed in 36 patients with total knee arthroplasty. Fifteen areas of interest
      were taken into consideration and their gammagraphic analyses were compared with
      radiologic findings during a postsurgery period of 24 months. Starting with a
      very high radionuclide uptake level obtained in the first postsurgery level, a
      gradual decrease was correlated with osteoblastic activity. In this first
      evaluation, the gammagraphic response around the implant is different in biologic
      prostheses than in cemented ones. These data may be useful for evaluating
      implants in orthopedic surgery.

PMID- 1395233
TI  - Intact articular cartilage cryopreservation. In vivo evaluation.
AB  - By varying the parameters that determine the cryopreservation process (freezing
      rate, storage temperature, cryoprotective agents, storage time), various
      protocols have been designed for preservation of osteochondral allografts of
      rabbit femoral condyles. The grafts were implanted orthotopically for three
      months. After harvesting, the results were evaluated by optical microscopy,
      histochemistry, and electron microscopy (scanning and transmission). A
      quantitative study and statistical analysis was performed using a gradation scale
      of chondral degeneration. Synovial reaction was higher in the fresh allograft
      than in the cryopreservation groups. Glycerol yielded better results than DMSO as
      a cryoprotective agent. No cryopreservation protocols produced the results equal
      to the control groups of either fresh auto- or allografts. Optimal preservation
      was achieved with either the group with hypothermic storage at 4 degrees for no
      more than 48 hours or the group with slow freezing to -80 degrees and preparative
      exposure to 15% glycerol at 4 degrees for 60 minutes. No statistically
      significant differences were found in these two groups.

PMID- 1395234
TI  - Ilizarov technique. Results and difficulties.
AB  - Of 100 cases treated by the Ilizarov method, 91 patients were reviewed from
      February 1985 to March 1990. There were 32 tibial fractures (29 open) and 21
      nonunions (nine infected). There were 47 cases of limb lengthening (28 tibia and
      19 femur). The results were as follows: good, 83%; fair, 13%; and poor, 4%.
      Slight and intermittent pain in some wire of the device was frequent (69%).
      Average bone healing time in tibial fractures was 4.95 months and 5.83 months in
      tibial nonunions. In bone-lengthening operations, the average lengthening index
      in the tibia was 1.02 months/cm (lengthenings ranged from 3 cm to 10 cm, with a
      mean of 5.71 cm), whereas in the femur, the average lengthening index was 1.14
      months/cm (lengthenings ranged from 3 cm to 7 cm, with a mean of 5.34 cm).
      Manually-tensed wires produced frequent problems (24.5%), whereas wire tensed by
      the dynamometric tensioner produced problems in only 7.8% of the cases. Despite
      good results, the Ilizarov technique requires adequate training to reduce an
      overall complication rate (approximately 30%).

PMID- 1395235
TI  - The value of preemployment roentgenographs for predicting acute back injury
      claims and chronic back pain disability.
AB  - Preemployment roentgenographs have long been used in industry to screen job
      applicants. Roentgenographs have had little effect, however, in curbing the cost
      of back problems in industry. This study evaluates the capabilities of
      preemployment roentgenographs for predicting acute back injury claims within the
      longshoring industry and for predicting back problems that lead to back
      disability of more than six months. The data indicate that lumbosacral
      roentgenographs are not helpful in predicting who is more likely to make a back
      injury claim, or those few who make up the vast majority of the costs for
      industrial back pain by becoming disabled for more than six months. Lumbosacral
      roentgenographs have little link to back disorders and may be viewed as
      discriminatory. The radiation exposure is not justified by their predictive value
      as a preemployment screening tool.

PMID- 1395237
TI  - Fracture of the body, neck, or spine of the scapula. A long-term follow-up study.
AB  - Fractures of the scapula are often considered benign lesions with a favorable
      outcome. The aim of the current study was to analyze the long-term results after
      fracture of the muscle-covered parts of the scapula: its body, neck, and spine.
      Sixty-eight patients were available for clinical examination 14 years after they
      had sustained a fracture of the scapula. The fractures had been treated with
      immobilization and early active motion. The follow-up rating was based on patient
      satisfaction and shoulder motion. Fifty-one patients were rated good, 15 were
      rated fair, and two were rated poor. Forty-eight shoulders were
      roentgenographically reexamined. Fourteen had a moderate and six had a pronounced
      deformity of the scapula. Scapula deformity was associated with pain in eight of
      the shoulders. The results of the current study suggest that the long-term course
      after fracture of the scapula is not uniformly favorable. Fifty percent of the
      patients with residual scapula deformity have shoulder symptoms. In most cases,
      however, the shoulder disablement is slight or moderate.

PMID- 1395236
TI  - Does the combined ventral derotation system (VDS) followed by Harrington
      instrumentation improve the vital capacity in patients with idiopathic double
      major curve pattern scoliosis? An analysis of 33 cases and review of the
      literature.
AB  - A young, homogenous population of 33 patients with idiopathic scoliosis of double
      major curve pattern (DMC), a mean thoracic curve of 70.6 degrees (standard
      deviation [SD] = 20.6), and a mean lumbar curve of 72.9 degrees (SD = 15), had a
      measurement of the vital capacity (VC) at rest before and at a minimum of one
      year after combined ventral derotation system (VDS). This was followed by
      Harrington instrumentation and fusion to evaluate the effect of scoliosis,
      kyphosis, and their surgical correction on VC at rest. A regression analysis
      showed that the VC was significantly lowered before operation to 69.6% of
      predicted value, whereas individuals with thoracic curvatures greater than 70
      degrees had a lower VC. The surgical correction of the thoracic curve of 50.8%
      and the lumbar curve of 68.4% was permanent in the follow-up evaluation, and the
      functional improvement in postoperative VC was 4.36%, statistically not very
      significant. The time between the two evaluations did have a significant
      statistical correlation with the observed improvement of the VC. The longer the
      interval between the two evaluations, the better the improvement of the VC. The
      age of the patient at the time of the first (VDS) operation influences the
      changes of the observed VC, significantly favoring the younger patients. The
      number of the functional vertebral segments included by the spinal
      instrumentation and fusion does not improve the VC.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1395238
TI  - Glenoid dysplasia. A case report and review of the literature.
AB  - Glenoid dysplasia is a rare congenital abnormality that may be associated with
      vague shoulder pain, limitation of motion, and weakness of the upper extremity.
      In many cases it is an incidental finding on chest roentgenogram, and high-level
      function is usually possible before the onset of symptoms or degenerative
      changes. The case of an 18-year-old collegiate football offensive lineman who
      developed symptoms secondary to previously undetected bilateral glenoid dysplasia
      is reported. Roentgenograms demonstrated dysplastic scapular necks, and
      arthrography showed a deformed, constricted shoulder capsule. Magnetic resonance
      imaging defined the extent of the cartilaginous anlage, and arthroscopy
      demonstrated progressive articular cartilage degeneration. Although treatment
      alleviated the shoulder symptoms at low-level activities, the patient was unable
      to successfully compete under the extreme demands of an American football
      lineman.

PMID- 1395240
TI  - Long-term results of total arthroplasty in adolescents with debilitating
      polyarthropathy.
AB  - The authors retrospectively reviewed 29 hip and 13 knee arthroplasties performed
      in 17 adolescents and young adults from 1973 through 1979. Most patients had
      severe multiple joint involvement; 16 had juvenile rheumatoid arthritis. Clinical
      and roentgenographic evaluations were performed before operation and at routine
      intervals for up to 11 years after operation. The average final follow-up
      evaluation was at ten years seven months. The modified Harris rating improved
      from 17 before operation to 68 at final evaluation. A dramatic improvement was
      noted in the ambulatory ability of 13 patients in whom increased joint motion and
      reduced deformity was observed at follow-up evaluation. At the 11-year
      roentgenographic review, 32% of hips had gross loosening, and an additional 39%
      had radiolucent lines greater than 2 mm in thickness in more than two
      radiographic zones. No lucency greater than 2 mm was noted in any of the knee
      replacements. Complications included one immediate collapse of the medial tibial
      plateau, four femoral fractures, one hip dislocation, and one case of
      arthrofibrosis. Despite untoward roentgenographic results and the high incidence
      of complications, total arthroplasty has dramatically improved the quality of
      life for these patients with multiple joint pathology. For this reason, the
      authors continue to recommend joint replacement in these individuals and the use
      of new prosthetic designs and surgical techniques.

PMID- 1395239
TI  - Acetabular roof reinforcement rings.
AB  - A series of 30 total hip arthroplasties was performed in 29 patients with the use
      of the Mueller roof reinforcement ring (RRR). The mean follow-up observation time
      was 30 months (standard deviation [SD] = 7.6). The clinical and radiologic
      results were evaluated according to the Mayo Clinic scoring system. The overall
      preoperative clinical score of 21.963 (SD = 18.776) points improved to a follow
      up examination score of 69.533 (SD = 11.599), a correction of 68.41%. The
      authors' goal in this series was to implant the ring together with the
      polyethylene socket as close to the anatomic position of the acetabulum as
      possible. There was no loosening of the RRR or the polyethylene sockets, nor was
      there material failure in the last evaluation of the hips. No statistically
      significant difference was found when the differences between the follow-up
      scores of the primary versus the revisionary procedures were compared. The roof
      replacement ring has been helpful for primary and revision arthroplasties of
      acetabular deficiencies occurring within five years after operation.

PMID- 1395241
TI  - Tissue growth into porous-coated acetabular components in 42 patients. Effects of
      adjunct fixation.
AB  - Histologic examination was performed on 42 uncemented, porous-coated acetabular
      components removed for reasons not related to fixation. Included were 20 devices
      that had fixed pegs or spikes to aid in initial fixation and 22 devices that used
      screws through the component. The diagnoses and patient ages at insertion, times
      in situ, and reasons for removal were comparable for the two groups. Bone
      ingrowth was observed in 28 of the 42 acetabular components (67%). Of the 20
      components with pegs or spikes, nine had no bone ingrowth, six had minimal bone
      ingrowth, four had moderate ingrowth, and one had extensive bone ingrowth. Of the
      22 components with screws, five had no bone ingrowth, six had minimal bone
      ingrowth, six had moderate bone ingrowth, and five had extensive bone ingrowth.
      Two of the devices with screws also had external threads on the metallic shell;
      neither had any bone ingrowth, and the two accounted for two of the five devices
      having no bone ingrowth in this group. Bone ingrowth occurred more frequently, in
      greater amounts and was more evenly distributed anatomically in cups using screws
      for initial adjunct fixation. Roentgenographic and clinical findings were
      unreliable in predicting ingrowth of bone.

PMID- 1395242
TI  - Efficacy of alumina ceramic heads for cemented total hip arthroplasty.
AB  - Fifty-seven cemented total hip arthroplasties (THAs) were reviewed in cases of
      osteoarthrosis secondary to congenital dysplasia or dislocation. The bearing
      surface of the prosthesis used in this series consists of a polyethylene
      acetabular component on an alumina ceramic head. All acetabular components were
      positioned at the same level as the original acetabulum, and an autologous
      femoral head graft was performed for 18 hips. The follow-up period ranged from
      five to eight years, averaging six years two months. The latest survey showed
      excellent and good results for 53 hips (92.9%). Four acetabular components (7%)
      and two femoral components (3.5%) showed roentgenographic evidence of loosening.
      Only one hip (1.8%) had to be treated with revision surgery for femoral component
      loosening. None of the cases suffered a broken ceramic head. The use of a total
      hip prosthesis with an alumina ceramic head in THA is likely to lead to excellent
      results for patients with osteoarthrosis of the hip.

PMID- 1395243
TI  - Osteon morphometry in females with femoral neck fractures.
AB  - The authors measured osteon dimensions and number in specimens of cortical bone
      obtained from the medial femoral neck (calcar) from nine female patients treated
      with hemiarthroplasty for femoral neck fractures, and from 12 (seven women, five
      men) age-matched cadavers without fractures. Specimens from the same location in
      14 (seven women, seven men) younger patients treated with total hip arthroplasty
      (THA) for osteoarthrosis were also studied. There were fewer osteons per unit
      area and the osteons and their Haversian canals were bigger in the fracture group
      than in the nonfracture or osteoarthritic groups. Patients with femoral neck
      fractures also exhibited a decreased Singh index and an increased intracortical
      porosity compared with age-matched normal controls. By contrast, the
      osteoarthritic group showed no difference in osteon or Haversian dimensions,
      osteon number per unit area, Singh index, or in porosity compared with the
      nonfracture group. These morphometric differences found in the cortical bone of
      the medial femoral neck may play a role in the incidence of fractures.

PMID- 1395244
TI  - Tibial tunnel placement in anterior cruciate ligament reconstructions and graft
      impingement.
AB  - Fifty-six anterior cruciate ligament (ACL) reconstructions had a magnetic
      resonance scan of the ACL graft six months after operation. The impingement-free
      grafts (n = 26) had a low magnetic resonance signal from origin to insertion.
      Impinged grafts (n = 30) had an increased magnetic resonance signal confined to
      the distal two thirds of the graft. The location of the tibial tunnel (TT) was
      determined from a lateral roentgenogram. Positioning the center of the TT 12-23
      mm from the anterior edge of the tibia consistently produced graft impingement
      and flexion contractures. Roof impingement was avoided and hyperextension was
      regained when the TT was centered more posteriorly within a 6-mm impingement-free
      zone (22-28 mm from the anterior edge of the tibia). Stability and knee extension
      were significantly better when the center of the TT was 2-3 mm posterior to the
      center of the normal ACL insertion.

PMID- 1395246
TI  - Advances in Spain.

PMID- 1395245
TI  - Open and arthroscopic synovectomy in hemophilic arthropathy of the knee.
AB  - Open and arthroscopic synovectomies of the knee in patients with classic
      hemophilia were evaluated with regard to effectiveness in reducing bleeding
      episodes, the effect on range of motion (ROM), and roentgenographic progression
      of hemophilic arthropathy. Eleven patients underwent 13 synovectomies (eight
      open, five arthroscopic). The average follow-up periods were 7.9 years and 2.2
      years for the open and arthroscopic groups, respectively. Both procedures
      significantly reduced recurrent hemarthroses. Knee ROM in the open synovectomy
      group was decreased or unchanged in 75% and minimally increased in 25%, whereas
      there was an increased in 80% and a decrease in 20% of the knees in the
      arthroscopic group. Furthermore, 62.5% of the knees required manipulation to
      improve ROM in the open synovectomy group, versus 0% in the arthroscopic group.
      Hemophilic arthropathy progressed in most knees in both groups. The arthroscopic
      group had a longer operative procedure (122 versus 59 minutes), but required less
      hospitalization (9.4 versus 23.1 days) and 25.6% less Factor VIII replacement.
      Both techniques reduce hemarthroses. There is usually a net loss of ROM with the
      open versus a net gain with the arthroscopic procedure, and roentgenographic
      progression hemophilic arthropathy is slowed but not halted after synovectomy.

PMID- 1395247
TI  - The snapping biceps femoris syndrome.
AB  - Snapping of tendons is a well-described entity in the literature, occurring
      mostly in athletes around the hip, ankle, shoulder, and elbow, but rarely the
      knee. A case of snapping of the biceps femoris tendon (BFT) in a patient with a
      painful knee and no history of trauma is described. An abnormal anterior
      insertion of the BFT was found to be the cause of the pain and snapping. Surgical
      treatment, reinsertion of the tendon in its anatomic position, completely
      corrected the abnormality, whereas conservative treatment failed.

PMID- 1395248
TI  - The long-term course of various meniscal treatments in anterior cruciate ligament
      deficient knees.
AB  - One hundred thirty-five patients were reviewed six to 16 years after anterior
      cruciate ligament repair or reconstruction. At follow-up evaluation, 60% of the
      patients demonstrated significant residual laxity on objective testing. Thirty
      percent of the patients reduced activity levels because of instability.
      Degenerative arthritis was noted to be more frequent in those patients who had
      been treated with total open meniscectomy than in those treated with arthroscopic
      partial meniscectomy, and it was more severe than in patients with intact
      menisci. Continued participation in high-stress sporting activities generally led
      to a high rate of further injuries, reoperations, and progression of
      osteoarthrosis.

PMID- 1395249
TI  - Semitendinosus Kennedy ligament augmentation device anterior cruciate ligament
      reconstruction.
AB  - This is a prospective study of 78 chronic unilateral isolated anterior cruciate
      ligament (ACL) patients who were treated with an arthroscopically-assisted
      reconstruction technique using the semitendinosus tendon, occasionally associated
      with the gracilis, augmented with the Kennedy-ligament augmentation device (LAD).
      There was a minimum two-year follow-up period (mean, 34.3 months; range, 24-50
      months). Ligamentous surgery was always restricted to the ACL intraarticular
      reconstruction. Preoperative, intraoperative, and postoperative examinations at
      three, six, 12, 18, and 24 months, and every year thereafter, including
      subjective and objective evaluation with KT 1000 arthrometer laxity measurements,
      were completed. Two-year examination data were available on 77 (98.7%) of the 78
      patients compared with preoperative data. The pivot shift (side-to-side
      difference) improved from 49.3% with Grade 0-1 to 92.2% with Grade 0-1. KT 1000
      20-pound anterior drawer (greater than 5 mm side-to-side difference) improved
      from 49.3% (mean, 6 mm) to 91.1% (mean, 0.55 mm). KT 1000 maximum manual anterior
      drawer (greater than 5 mm side-to-side difference) improved from 21.9% (mean, 7.8
      mm) to 97.4% (mean, 0.55 mm). After ACL reconstruction, 89.6% of patients had a
      full range of motion and only 10.3% had flexion contractures of less than 5
      degrees; 5.2% of patients had mild effusion. Functional Lysholm knee scoring of
      100 points improved from 7.7% scoring over 85 points preoperatively (mean, 66.5)
      to 92.1% postoperatively (mean, 95.6). Instability was controlled in 89.4% of the
      patients, and 71.4% have been involved in sports after injury. Anterior cruciate
      ligament reconstruction reduces pathologic laxity, improves lower-leg function,
      and minimizes flexion contracture and effusion.

PMID- 1395250
TI  - The Leeds-Keio prosthesis in chronic anterior cruciate deficiency.
AB  - A woven polyester graft is used in chronic anterior cruciate instability. Twenty
      five patients were reviewed with an average follow-up period of almost five
      years. The patients were assessed in terms of function, clinical examination, and
      residual laxity. The results showed that four could be classified as excellent,
      16 good, and four poor. Fifty-two percent of patients returned to their
      preaccident level of activity, and there did not appear to be any evidence of
      increasing laxity with time. All patients had a good range of flexion with no
      extension loss. This prosthesis, along with its unique method of fixation, offers
      a simple alternative to patellar tendon or soft tissue reconstructions in the
      chronic anterior cruciate-deficient knee.

PMID- 1395251
TI  - Revision surgery in clubfeet.
AB  - The reoperated clubfeet of 29 children aged one to 12 years were reviewed. The
      surgical procedure most often used in revision surgery was recomplete soft-tissue
      release alone or combined with plantar release, calcaneocuboid fusion, and
      capsulotomies of the navicular-first cuneiform-first metatarsal joint. In 27 of
      29 feet, acceptable results were achieved. Nineteen were excellent and good
      results. An algorithm that suggests surgical solutions to a variety of clubfoot
      deformities in different age groups has been developed, as well as an objective
      rating system, to evaluate the long-term results of revision surgery of clubfeet.

PMID- 1395252
TI  - Subtrochanteric fractures of the femur. Results of treatment by interlocking
      nailing.
AB  - Ninety-five subtrochanteric femoral fractures were treated with an interlocking
      nail. There were 69 closed and 26 open fractures. This injury was the result of
      high-energy trauma in 77% of the cases. The average time to healing was 25 weeks.
      There were three delayed unions, one nonunion, and six malunions. Essentially all
      nonpathologic, subtrochanteric femur fractures can be stabilized by interlocking
      nailing, regardless of the fracture pattern or degree of comminution. Favorable
      mechanical characteristics of interlocking nails have eliminated the requirement
      of surgically reconstituting the medial femoral cortex. Closed interlocking
      nailing is the preferred treatment for subtrochanteric fractures of the femur
      resulting from trauma.

PMID- 1395253
TI  - Proximal femoral bone density and its correlation to fracture load and hip-screw
      penetration load.
AB  - The bone mineral density of 22 random, fresh proximal human femora was estimated
      by roentgenography using the Singh index (SI) and measured using a regional bone
      mineral density computed tomographic protocol. Uniaxial compression was used to
      produce an impacted subcapital fracture. The femoral heads then were isolated and
      mounted on a sliding screw plate compression device and loaded to failure in a
      push-out or hip-screw penetration mode. Wide intraobserver variation, poor
      reproducibility, and poor prediction of the experimental fracture properties of
      the proximal femur were noted for SI values. Regional bone mineral density
      provided a reliable estimate of both the gross fracture loads and hip-screw
      penetration loads. In addition, there was a high correlation between trabecular
      density and the experimental fracture properties of the proximal femur.
      Therefore, The validity of the SI as an indicator of the mechanical properties of
      the proximal femur should be reconsidered.

PMID- 1395254
TI  - Rupture of the symphysis pubis during labor.
AB  - Two cases of spontaneous rupture of the symphysis pubis (SP) during delivery are
      reported. The separations were associated with considerable pain, swelling, and
      tenderness over the symphysis pubis and were confirmed roentgenographically. Both
      patients were treated conservatively with bed rest, mostly in the lateral
      decubitus position, within pelvic binders. Immobilization was discontinued when
      they were pain free. The SP separations remained in reduced positions. The
      patients were essentially asymptomatic and walked normally. Conservative
      treatment followed by early mobilization is adequate treatment for SP
      separations.

PMID- 1395255
TI  - Femoral artery thrombosis after open reduction of an acetabular fracture.
AB  - The increasingly popular ilioinguinal anterior approach for select fractures of
      the acetabulum provides excellent exposure with minimal soft tissue dissection.
      Vascular complications reported with this procedure, although infrequent, are
      usually quite pronounced in their presentation. The authors encountered a more
      subtle case of femoral artery thrombosis secondary to vessel retraction while
      using this approach. The susceptibility of major vessels to thrombus formation is
      noteworthy. The precautions, and the close postoperative monitoring necessary to
      detect such vascular lesions, are emphasized.

PMID- 1395256
TI  - Reversible vasospasm in association with the use of heparin and
      dihydroergotamine.
AB  - A case of reversible vasospasm is reported in a 54-year-old man with a closed
      bimalleolar ankle fracture. On admission the patient had normal distal pulses and
      laboratory studies. He was a heavy smoker who continued to smoke in the hospital.
      Deep venous thrombosis (DVT) prophylaxis included dihydroergotamine and heparin
      (DHE-H). In the early postoperative period, marked spasm of all three arteries
      developed on the operative side. Smoking privileges and DHE-H were discontinued.
      The vasospasm resolved after intraarterial nitroglycerin. This case suggests an
      infrequent but potentially limb-threatening complication of DHE-H.

PMID- 1395257
TI  - A simultaneous distal phalanx avulsion fracture with profundus tendon avulsion. A
      case report and review of the literature.
AB  - Avulsion injuries of the flexor digitorum profundus are fairly common injuries,
      yet simultaneous avulsion fractures of the insertion of this tendon associated
      with rupture of the tendon from the bony fragment is rarely described and is more
      complicated. In the 24-year-old athlete, the injury was classified according to
      the system of Leddy and Packer. The authors' method of treatment is also
      described. Similar cases presented in the literature are reported, with emphasis
      on pathomechanism, physical findings, and surgical repair method. In this rare
      injury, stabilization of the distal interphalangeal joint is necessary even at
      the expense of early motion.

PMID- 1395258
TI  - Proximal tibial skeletal traction for femoral shaft fractures in children.
      Treatment to discard or retain.
AB  - A proximal tibial skeletal traction in the treatment of femoral shaft fractures
      in the growing child has been reported to result in complications such as knee
      pain, knee joint subluxation, and growth disturbance. For the last 15 years, the
      authors used a single screw (instead of the Kirschner wire) inserted in the tibia
      perpendicular to the surface and well below the tibial tubercle physis. With the
      traction applied to this screw and the leg in a 90-90 position or resting on a
      Braun splint, none of the previously described complications were observed. This
      modification of the proximal tibial skeletal traction is a simple, quick, and
      safe method in the treatment of femoral shaft fractures in children.

PMID- 1395259
TI  - Primary Hodgkin's disease of bone. A report of two cases in adolescents and
      review of the literature.
AB  - The presentation of Hodgkin's disease as a primary bony lesion is unusual.
      Seventeen such cases have been reported, only three of which appear in the
      orthopedic literature. The prognosis for survival in these patients is poor,
      possibly because of difficulty in arriving at the correct early diagnosis. In two
      adolescent girls (ages 12 and 17) with primary Hodgkin's disease of bone, the
      diagnosis was made with uncertainty or delay. One of the patients died and the
      other has progressive disease, two and one-half years after the diagnosis was
      established. Earlier recognition may lead to better outcomes.

PMID- 1395260
TI  - Magnetic resonance imaging of pigmented villonodular synovitis in subtalar joint.
      Report of a case.
AB  - Pigmented villonodular synovitis (PVNS) is rare in the foot; however, it
      developed in the subtalar joint extending around the ankle of a 24-year-old man.
      The diagnosis was made by a combination of clinical findings, most notably the
      aspiration of the synovial fluid. Magnetic resonance imaging was most useful in
      showing the extent of the soft-tissue mass before surgery. Low-signal intensity
      of the mass, featured on both T1- and T2-weighted images, was suggestive of PVNS.

PMID- 1395261
TI  - Tibial rotational osteotomy for idiopathic torsion. A comparison of the proximal
      and distal osteotomy levels.
AB  - A retrospective analysis was done of 52 rotational tibial osteotomies (RTOs)
      performed on 35 patients with severe idiopathic tibial torsion. Thirty-nine
      osteotomies were performed at the proximal or midtibial level. Thirteen were
      performed at the distal tibial level with a technique previously described by one
      of the authors. Serious complications occurred in five (13%) of the proximal and
      in none of the distal RTOs. For severe and persisting idiopathic tibial torsion,
      the authors recommend correction by RTO at the distal level. Proximal level
      osteotomy is indicated only when a varus or valgus deformity required concurrent
      correction.

PMID- 1395262
TI  - Why do most surgical incisions require lengthening? How to avoid it.
AB  - When an incision is retracted, it shortens because skin does not actually stretch
      -it only shifts. A mathematical model accurately predicted operating room
      experience. Average retraction of 30-50% shortens an incision by 15%. Therefore,
      an incision to expose fixed bony landmarks should be 15% longer than the distance
      between them.

PMID- 1395263
TI  - Biomechanical effects of a new point configuration and a modified cross-sectional
      configuration in Kirschner-wire fixation.
AB  - Kirschner-type wires (K-wires) comprising three different point configurations
      and two cross-sectional shaft configurations were drilled into bone to determine
      the insertional force required and the holding power achieved with each type.
      Round K-wires with either a diamond point or a high rake-angle trocar point were
      compared with each other and with C-wires, which have a rounded square cross
      section and a short diamond point. The K-wires performed superiorly to C-wires
      with respect to bone penetration. The K-wires demonstrated about twice as much
      holding power as the C-wires. No significant differences in performance were
      detected between the diamond-tipped and trocar-tipped K-wires with respect to
      either insertion or pull-out. For all three wire-tip combinations, insertion was
      facilitated by faster drill speed, but holding strength was superior with slower
      speed. For ease of insertion, even at oblique angles, and for maximum holding
      strength, the high-rake angle, trocar-tipped K wire is best.

PMID- 1395264
TI  - Effect of electrostimulation on denervated muscle.
AB  - The influence of electrostimulation on denervated and reinnervated muscle was
      investigated. First, the left peroneal nerve was severed in rats. Wet weight and
      muscle fiber diameter of denervated anterior tibial muscle was compared as a
      percentage of contralateral muscle in stimulated and non-stimulated rats. In a
      second experiment, four weeks after the peroneal nerve was severed, the tibial
      nerve was cross-sutured to the distal stump of the peroneal nerve.
      Electrostimulation was continued in rats that had electrostimulation before nerve
      crossing. Recovery of wet weight was assessed at eight weeks and at one year
      after nerve-crossing. The mean decrease in weight and fiber diameter of the
      denervated muscle was significantly less in the group that was electrostimulated
      for eight weeks. Recovery of weight of reinnervated muscle was significantly
      better in the electrostimulated group. Electrostimulation of denervated muscle
      retarded denervation atrophy and improved recovery after reinnervation.

PMID- 1395266
TI  - New Jersey low-contact stress total knee arthroplasties (TKAs)

PMID- 1395267
TI  - Surgical treatment of the child's flatfoot.
AB  - A series of 234 surgically treated flatfoot in children were treated by means of
      a double incision and by the placing of an orthosis in the sinus tarsi.

PMID- 1395265
TI  - Articular cartilage thickness and glycosaminoglycan distribution in the canine
      knee joint after strenuous running exercise.
AB  - The influences of the strenuous running training program on the knee joint
      articular cartilage was studied in six female beagle dogs. At the age of 15
      weeks, the dogs started running on a treadmill inclined 15 degrees uphill.
      Thereafter, the dogs were trained for 40 weeks, five times a week. For the final
      15 weeks, the dogs ran 20 km/day. Six age-matched female beagles served as
      controls. The cartilage surfaces were intact after the running exercise. The
      training reduced the thickness of the uncalcified cartilage by 6% in the medial
      femoral condyle. The glycosaminoglycan concentration was reduced an average of
      11% on the summits of the femoral condyles. The reduction was most pronounced
      (41%) in the superficial 50-micron cartilage zone. In other regions of the knee,
      such a decrease of glycosaminoglycans was not observed. A shift to strenuous
      running voided the increase in cartilage thickness and proteoglycan content
      previously observed after moderate running. Strenuous running induced marked
      depletion of proteoglycans from the superficial layer of the femoral condyles at
      sites subjected to highest impact loads.

PMID- 1395268
TI  - LD hip arthroplasty. Design concepts and first clinical trials of a new modular
      system.
AB  - The new LD modular hip arthroplasty is made of Ti6A14V. The acetabular component
      has a hemispheric expansive metallic ring and a polyethylene nucleus in the shape
      of a cone segment. Since June 1988, when the clinical trials began, 352
      arthroplasties have been performed with 112 total hip arthroplasties among them.
      Only 60 noncemented total hip arthroplasties, with the longest follow-up
      evaluation reaching 24 months, were analyzed. Patients with revision operations
      were excluded. The results have been evaluated using the Merle D'Aubigne scoring
      scale. Good results were found in 86% of cases. Pain improved markedly at three
      months in the postoperative period. At six months, the Trendelenburg sign was
      negative in 76% and positive in 12%. The Duchenne sign was positive in 11%. Major
      complications included three dislocations, two acetabular component revisions
      caused by initial malposition, one external popliteal nerve palsy, one deep
      infection, and two periprosthetic fractures. No acetabular migrations have been
      found. There are six femoral sinkings of less than 1 cm. Heterotopic
      ossifications Grade II-III appear in 24% of cases. The results to date are
      evaluated clinically and radiologically. The acetabular design has proved
      efficient, and the femoral components show a low incidence of stress shielding.

PMID- 1395269
TI  - Experimental production of heterotopic bone. 1946.

PMID- 1395270
TI  - Five-year follow-up evaluation of the noncemented press-fit titanium hip-joint
      endoprosthesis.
AB  - A series of 260 noncemented total hip arthroplasties with a titanium alloy stem
      and fixation by the Zweymuller press-fit and an Endler polyethylene threaded cup
      was reviewed in detail. The minimum follow-up period was 48 months and the
      maximum 72 months, with an average of 60 months. A scale from zero to five points
      was applied to evaluate pain, mobility, and motion for a total possible
      accumulation of 15 points. The global results of the different etiologic groups
      (arthrosis, femoral head necrosis, rheumatoid arthritis, and subcapital hip
      fractures) have been very good and good (12-15 points) in 67.5% of the cases and
      fairly good and bad in 32.3%. These results have been better in femoral head
      necrosis than in arthrosis or rheumatoid arthritis, but not as good in subcapital
      hip fractures. The age groups below 60 had better results than the above 60
      groups. The Singh index higher than 3 was correlated with better-than-average
      results. The polyethylene cup migrated horizontally (more than 4 mm) in 7.6% of
      the cases and vertically (more than 5 mm) in 10%. The non-evolutionary cortical
      remodelation of the femur does not influence the results. Prosthetic stem sinking
      less than 4 mm has been found in 62% of the cases, from 4 to 9 mm in 21%, and
      greater than 9 mm in 6%. No alterations with clinical consequences attributable
      to stress-shielding have been detected.

PMID- 1395271
TI  - Experience in replacements of hip prosthesis.

PMID- 1395272
TI  - Occipital-cervical instability.
AB  - A retrospective clinicoroentgenographic study was done on 26 patients with
      atlantoaxial instability, 17 traumatic and nine nontraumatic. All were treated by
      means of surgical C1-C2 and occipital-C2 stabilization. The traumatic instability
      was associated with lesions of the odontoid process and the atlas transverse
      ligament. Instability may be endogenous or associated with fracture of the atlas.
      Surgical indication was determined by the level of the fracture line, neurologic
      symptoms, age, and presence of multiple lesions. C1-C2 stabilization by means of
      wiring and iliac graft was the selected treatment. Fusion between the occipital
      and C2 segment was indicated in case of irreducible dens pseudoarthrosis.
      Fracture on the os odontoideum was very unstable and required greater C1-C2
      fusion. Nontraumatic C1-C2 instability was either congenital or secondary to
      pathologic fractures. Rheumatoid arthritis, which produces anterior displacement
      of the atlas over the dens to more than 10 mm, neurologic symptoms, or
      untreatable pain must be stabilized by means of C1-C2 fusion. When elevation of
      the dens or irreducible displacement of the atlas exists, the results were
      relatively poor. Tumorous instability produced pathologic fracture of the body of
      the axis and had to be treated with C1-C2 wiring on bone cement. Down's syndrome
      instability required occipitoaxial fusion and strict postoperative
      immobilization.

PMID- 1395273
TI  - Clinical and ultrastructural analysis of failures in chemonucleolysis.
AB  - A series of 12 patients with failed chemonucleolysis were analyzed to determine
      the various causes of such failures. The ultrastructural findings observed in
      laminectomy specimens did not account for the failure in the enzyme treatment.
      The findings suggested deficient cellular nutrition secondary to enzymatic
      histolysis of the nucleus pulposus.

PMID- 1395274
TI  - Internal fixation of ulnar fractures by locking nail.
AB  - Fractures and dislocations of the forearm are commonly observed in trauma
      clinics. With time, there will probably be significant increases in fractures of
      the forearm associated with traffic and sports. The efficacy of the treatment of
      ulnar fractures by a new locking nail, developed by Lefevre in Strasbourg, was
      tested in 20 patients. The fractures were severely displaced ulnae or both bones
      of the forearm. The minimum follow-up period was six months. The average age of
      the patients was 33.5 years (range, 14-77 years). The nail is placed into the
      ulna proximally. Locking is achieved by two screws placed at the proximal and
      distal end of the nail. The healing time for the fractures of both bones of the
      forearm ranged from 75 days to 20 weeks, with an average of 15 weeks. Healing
      time for the ulnar fractures ranged from eight to 20 weeks, with an average of
      ten weeks. The advantages of this nail were easy closed technique, compression
      effects at the fracture site, and enough stability so that an external support
      and tourniquet, in isolated ulnar fractures, were not necessary.

PMID- 1395275
TI  - Treatment of the femoral and tibial fractures with Grosse and Kempf locking
      nails.
AB  - In a series of 104 femoral and 50 tibioendomedullary nailings using Grosse-Kempf
      (G-F) locking nails, 24% of femoral fractures and 12% of tibial fractures were
      comminuted; 48% of the patients had multiple injuries. The nail was locked at
      proximal and distal levels in 54% of the cases for the femur. Dynamization of the
      nail was carried out at an average of 12 weeks. Nonweight-bearing was imposed for
      both series from three weeks to three months. Bone healing was achieved before
      six months in 100% of tibial fractures. Following Thoressen criteria, the results
      of femoral cases were all excellent and good; the percentage reached 96% for
      tibial cases. The G-F nail is suitable for high-energy, comminuted fractures.

PMID- 1395276
TI  - Condylocephalic nailing in pertrochanteric fractures.
AB  - Because of the spectacular increase in the number of fractures of the proximal
      end of the femur, especially in the elderly, there is a great interest to find
      surgical techniques that are simple, decrease mortality, and restore early the
      functional status of the patients, thus reducing the hospital stay. From 1969
      until 1989, 2660 fractures were treated with the Kuntscher condylocephalic (KC)
      nail. The mean age of patients was 79 years, and the general condition was
      considered to be good in only 23%. Death in the ensuing three months occurred in
      12.5%. Complications of the technique were supracondylar fractures (1.8%) and
      migrations of the nails (17.4%). Bone healing occurred at eight to 12 weeks. Only
      15% of patients failed to walk. Mean cervicodiaphyseal postoperative angle was
      155 degrees. As compared with other surgical techniques, the KC nail was easier
      to insert, in relatively less operating time, and knee problems of Ender's nail
      operations can be avoided. The KC nail was most suitable for the treatment of
      pertrochanteric fractures in elderly patients.

PMID- 1395278
TI  - Complications of anterior cervical disk removal and fusion.
AB  - Surgeons favoring fusion believe that removal of the disk alone can result in
      painful spondylosis, eventually requiring fusion. Surgeons not favoring fusion
      eliminate painful neuralgia from damage to the anterior femoral cutaneous nerve
      as well as painful donor site scars. Also eliminated are painful pseudarthrosis
      and degenerative problems. Graft collapse and displacement are uncommon if three
      sided iliac grafts are used. Rarely, if ever, is it necessary to fix the graft in
      place with wire silk sutures. Fortunately, complications of cervical spine
      surgery are uncommon.

PMID- 1395277
TI  - Correction of angular deformities by physeal distraction.
AB  - Physeal distraction is an alternative to more conventional treatments for the
      correction of angular deformities of the long bones. Twenty deformities of the
      femur and tibia, nine of which also involved associated shortening, were
      partially or completely corrected. In eight cases, there was physeal bony bridge.
      Complete correction of the angular deformity was achieved in 17 patients, and in
      seven patients, more than 80% correction was achieved. There were complications
      in four patients that hindered complete correction of the deformity, or
      shortening, or both. The external control of the correction until consolidation
      occurs is progressive and fairly noninvasive. The method allows external control
      of the correction until consolidation; it acts at the site of the deformity
      itself and permits lengthening and angular correction during therapy. In
      deformities with a physeal bony bridge, correction can be achieved with physeal
      distraction alone, prior resection of the bridge is not unnecessary. The
      technique is indicated in cases of angular deformities in patients nearing
      skeletal maturity and particularly in subjects in whom there is associated
      shortening.

PMID- 1395279
TI  - Posterolateral lumbar and lumbosacral fusion with and without pedicle screw
      internal fixation.
AB  - Forty-seven patients who had lumbar or lumbosacral fusion with or without pedicle
      screw internal fixation by one surgeon for treatment of degenerative lumbar
      disease with clinical instability were retrospectively reviewed by an independent
      observer. Eighteen of the 21 patients whose fusions were internally fixed with
      the Variable Spinal Plating (VSP) system were available for review. A control
      group consisted of 27 patients who had fusion without internal fixation. The rate
      of pseudarthrosis did not significantly differ between the two groups (VSP group,
      22%; versus control group, 26%). Twelve (67%) of the 18 patients treated with
      fusion and VSP instrumentation were considered to have had a good or excellent
      outcome, whereas 19 (70%) of the 27 patients treated by fusion without internal
      fixation had good or excellent results. Two VSP-instrumented patients had
      postoperative leg dysesthesias, whereas this complication was not observed in the
      control group. Bilateral posterolateral lumbar or lumbosacral fusion without
      internal fixation is as effective as and safer than fusion with pedicle screw
      instrumentation.

PMID- 1395280
TI  - An electromyographic analysis of the shoulder during cones and planes of arm
      motion.
AB  - Shoulder motion has traditionally been described in reference to arbitrarily
      defined planes of motion (e.g., sagittal/flexion, coronal/abduction). This study
      examined shoulder muscle recruitment during conical arm movements, which include
      all planes of motion. Electromyographic (EMG) data was collected with
      intramuscular wire electrodes from ten muscles in five normal volunteers. Each
      muscle showed peak EMG activity in association with a direction of action
      consistent with its anatomic alignment. These findings were similar for movements
      in both the sagittal and coronal planes, calling into question conventionally
      held designations of shoulder muscles as flexors and abductors. Muscle
      recruitment was as follows: Clavicular pectoralis major, to move the arm medially
      along the horizontal; anterior deltoid, to move the arm obliquely upward inclined
      toward the midline; middle deltoid, to move the arm obliquely upward inclined
      away from the midline; posterior deltoid, to move the arm laterally along the
      horizontal; and teres major and latissimus dorsi, to move the arm obliquely
      downward away from the midline. Rotator cuff muscles were maximally active during
      elevation, consistent with the concept of a force couple.

PMID- 1395281
TI  - Incomplete rotator cuff tears. Results of operative treatment.
AB  - Thirty-eight shoulders of 36 patients with incomplete rotator cuff tears
      surgically repaired were evaluated, with an average follow-up period of 4.9
      years. The average age at operation was 52.2 years. Three types of incomplete
      tears were identified: superficial (12 shoulders), intratendinous (three), and
      deep surface tears (23). Full-thickness cuff involving the lesion was resected
      and repaired by side-to-side suture (13 shoulders), side-to-bone suture (eight),
      fascial patch grafting (16), or side-to-bone suture with fascial patch grafting
      (one). The overall results were satisfactory in 31 shoulders (82%). The results
      were not affected by the tear types, operative methods, or follow-up period. The
      patients with poor results were associated with major complications other than
      rotator cuff tears or with insufficient resection of the damaged cuff. When the
      full-thickness cuff involving the lesion is completely resected and repaired,
      long-term satisfactory results can be anticipated in a high percentage of
      patients regardless of tear types.

PMID- 1395282
TI  - Autotraction stress roentgenography for demonstration anterior and inferior
      instability of the shoulder joint.
AB  - A form of stress roentgenography is presented for the diagnosis of anterior and
      inferior shoulder instabilities. Stress is induced by anterioinferior traction
      concentrated on the shoulder during extension of the flexed hip, when patients
      hold their legs on the side being examined, with both hands. The anterior and
      inferior shifts of the humeral head in relation to the glenoid fossa then are
      measured from anteroposterior and modified axillary roentgenograms. This method
      was employed in 16 shoulders with recurrent anterior dislocation, 11 recurrent
      anterior subluxations, nine multidirectional instabilities, and 19 control
      shoulders. Mean anterior translations were 3 mm and 5 mm, and inferior
      translations were 7 mm and 10 mm for the control and recurrent dislocation
      groups, respectively. There were statistically no significant differences between
      those groups. In the recurrent anterior subluxations, the corresponding
      translations were of a completely different order, 21 mm and 19 mm, respectively,
      allowing the distinction from the controls and recurrent anterior dislocations in
      most cases. The shifts found in multidirectional instabilities, averaging 27 mm
      and 26 mm, respectively, were significantly greater than for the recurrent
      subluxations, but the differences were not great enough for accurate differential
      diagnosis in individual cases. Autotraction stress roentgenography of the
      shoulder may be of use in the diagnosis of recurrent anterior subluxations and
      anteroinferior multidirectional instabilities. It also gives good general views
      of the looseness of the glenohumeral joint.

PMID- 1395283
TI  - Neurologic complications and lumbar laminectomy. A standardized approach to the
      multiply-operated lumbar spine.
AB  - Even the careful and knowledgeable spine surgeon will encounter a variety of
      neurologic complications during and after routine lumbar laminectomy. These
      include dural and nerve root injuries; cauda equina syndrome; and formation of
      scar tissue, extradural and intradural (arachnoiditis). The surgeon must be
      prepared to identify each of these problems and deal with them effectively at the
      time of the procedure and in the immediate postoperative and follow-up periods.
      The physician evaluating the multiply-operated lumbar spine patient must use an
      organized approach. The origin of the problem in most instances is a faulty
      decision to perform the original operative procedure. Further surgery on an
      "exploratory" basis is not warranted in any situation and most likely will lead
      only to further disability. There should be definite objective findings to
      substantiate the patient's symptoms. The etiology of each patient's symptoms.
      must be accurately localized and identified. Medical status and psychosocial
      situation--as well as orthopedic and neurologic findings--should be evaluated at
      the time of the initial consultation. Once the spine is identified as the
      probable source of symptoms, specific features should be sought in the patient's
      clinical history, physical examination, and roentgenographic studies. The number
      of previous operations, length of pain-free interval, and predominance of leg
      versus back pain are the major historic signposts. The presence of a tension sign
      and the neurologic findings are the focal points of the physical examination.
      Plain roentgenograms, motion films, water-soluble myelogram, computed axial
      tomography, and magnetic resonance imaging with contrast have specific roles in
      the workup.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395284
TI  - Fluoroscopic comparison of kinematic patterns in massive rotator cuff tears. A
      suspension bridge model.
AB  - Twelve shoulders with known massive rotator cuff tears were imaged
      fluoroscopically. The observed kinematic patterns were correlated with the known
      locations of the rotator cuff tears. Three kinematic patterns emerged: Type I,
      stable fulcrum kinematics associated with tears of the superior rotator cuff
      (supraspinatus and a portion of the infraspinatus); Type II, unstable fulcrum
      kinematics associated with tears that involved virtually all of the superior and
      posterior rotator cuff; and Type III, captured fulcrum kinematics associated with
      massive tears that involved the supraspinatus, a major portion of the posterior
      rotator cuff, and a major portion of the subscapularis. In Type III, an "awning
      effect" of the acromion was observed to influence active motion. Based on the
      recorded kinematic patterns, a biomechanical model was developed comparing the
      rotator cuff tear to a suspension bridge (loaded cable). A biomechanical analysis
      of forces acting on the rotator cuff according to this model yielded data that
      supported the contention that certain rotator cuff tears in older individuals may
      be adequately treated with debridement and decompression, without repair.

PMID- 1395285
TI  - Irreducible "pulled elbow" in a child. A case report.
AB  - "Pulled elbow" is a common pediatric injury that occurs when axial traction is
      applied to an arm that is extended while the forearm is pronated. These forces
      can create a transverse tear in the annular ligament, which permits subluxation
      of the radial head. In most cases, closed reduction can be performed by
      supinating the forearm and flexing the elbow. In the case of a five-year-old boy,
      surgical reduction of this injury was necessary to reduce the subluxated radial
      head.

PMID- 1395286
TI  - Osteochondritis dissecans of the elbow. A long-term follow-up study.
AB  - Thirty-one patients with osteochondritis dissecans of the capitellum humeri were
      followed for an average of 23 years. There were symptoms in about half of the
      elbows at the follow-up examination. Impaired motion and pain on effort were the
      most common complaints. Roentgenographic signs of degenerative joint disease were
      present in more than half of the elbows and correlated with a reduced range of
      motion. The diameter of the radial head increased in comparison with the
      contralateral elbow in two thirds of the patients.

PMID- 1395287
TI  - The fallen wire sign. An indicator of hip prosthetic loosening.
AB  - Trochanteric osteotomy is commonly performed during total hip arthroplasty.
      Subsequent fatigue fracture of the osteotomy wires, although common, usually has
      no clinical sequelae. In four cases, wire fragments migrated down the medullary
      cavity of the femur, in the space created by a loosened femoral component. This
      roentgenographic observation seems not to have been previously reported and is a
      definitive sign of femoral prosthesis loosening.

PMID- 1395288
TI  - Cementless total hip arthroplasty in renal transplant patients.
AB  - Twenty-seven cementless total hip arthroplasties were performed in 17 steroid
      dependent renal transplant patients. The average age at operation was 39 years,
      and the average daily dose of prednisone was 10.9 mg. At a mean of 48 months post
      surgery, all patients had good to excellent hip ratings on clinical examination
      and the results compared favorably with 235 non-steroid-dependent age-matched
      patients using the identical prosthetic hip system. The results of this study
      suggest that long-term immunosuppression does not prevent bone ingrowth.
      Noncemented total hip arthroplasty appears to be a reasonable therapeutic option
      for end-stage osteonecrosis in steroid-dependent renal transplant patients.

PMID- 1395289
TI  - Hip fracture-dislocation with transepiphyseal separation. Case report and
      literature review.
AB  - Fracture-dislocation of the hip is an infrequent injury in adolescence. In
      combination with transepiphyseal separation of the capital femoral epiphysis, the
      injury is rare and catastrophic. A review of orthopaedic literature shows varied
      recommendations as to treatment approaches. The most recent articles have
      suggested that open reduction through a posterior approach and internal fixation
      is the best way to treat this problem initially. Later reconstructive measures
      are usually required because this injury often leads to avascular necrosis of the
      femoral head. The patient and family should be advised that the prognosis after
      such a fracture-dislocation is not good. Potential reconstructive measures after
      collapse of the femoral head include total hip arthroplasty and hip arthrodesis.
      Total hip arthroplasty is not a reliable means of providing a long-term painless
      joint in an active adolescent with one-joint disease. Hip arthrodesis has been
      shown to be a good alternative treatment for patients who develop avascular
      necrosis after this severe injury.

PMID- 1395290
TI  - Hip pain caused by buttock claudication. Relief of symptoms by transluminal
      angioplasty.
AB  - Two patients with severe hip pain proved to have buttock claudication resulting
      from isolated stenosis of the hypogastric artery. This diagnosis may be elusive
      if distal pulses are palpable, directing the clinician's suspicion away from
      vascular pathology. Diagnosis requires angiography. The patients were
      successfully treated by transluminal angioplasty. Angioplasty is the initial
      treatment of choice for these patients because the hypogastric artery is usually
      readily and safely accessible from either the femoral or axillary artery.

PMID- 1395291
TI  - Effect of functional neuromuscular stimulation on anterior tibial compartment
      pressure.
AB  - Intramuscular pressures in the anterior tibial compartment were measured in five
      paraplegic subjects who used functional neuromuscular stimulation (FNS) by
      percutaneous intramuscular electrodes for exercise and walking. Effects of two
      types of stimulation pattern were tested: continuous stimulation for 15 minutes
      and cyclic stimulation for 60 minutes, with duty cycle and stimulation levels
      similar to that used in walking. Resting compartment pressure levels before
      stimulation were less than 7 mm Hg in all subjects. Continuous stimulation at
      maximum parameters produced compartment pressure levels up to 116 mm Hg, but
      these were not sustained. They decreased to below 40 mm Hg within one minute in
      all except one subject, who was having repeated spasms. Cyclical stimulation
      raised mean muscle pressure to between 70 and 80 mm Hg in two patients. Muscle
      contraction pressure increased to 153 mm Hg in one patient, but was below 100 mm
      Hg in all patients after two minutes, except during spasms. Muscle relaxation
      pressure stayed below 30 mm Hg in four subjects. After stimulation, the pressure
      returned to prestimulation levels within 15 minutes. These results suggest that
      FNS subjects are not in danger of developing compartment syndrome. Nevertheless,
      occasional testing of compartment pressures is recommended, especially when
      activity levels rise significantly.

PMID- 1395292
TI  - Forced march-induced peroneal compartment syndrome. A report of two cases.
AB  - Isolated exertional peroneal compartment syndrome is rare. Two cases are
      described after prolonged forced march in highly conditioned United States
      Marines. Measured compartment pressures were over 100 mm Hg. No permanent
      impairment resulted after surgical decompression.

PMID- 1395293
TI  - Posterior tibial subluxation of the posterior cruciate-deficient knee.
AB  - Ten subjects with unilateral posterior cruciate ligament-deficient knees were
      studied, comparing the knee mechanics of the affected knee with the mechanics of
      the opposite normal knee. The static squat test was used to determine knee forces
      and moments through measurements made on roentgenograms. Statistically
      significant increases occurred in posterior translation of the tibia in all knees
      at high knee flexion angles, but not uniformly at low knee flexion angles. The
      results suggest that posterior tibial subluxation occurs in vivo during certain
      activities of daily living. Posterior tibial subluxation occurred in positions of
      knee flexion near 70 degrees, establishing a new equilibrium for the system where
      tibiofemoral joint compression force (approximately four times one-half body
      weight) remained an order of magnitude greater than tibiofemoral shear forces
      (approximately 10% of one-half body weight).

PMID- 1395294
TI  - Results following treatment of traumatic dislocations of the knee joint.
AB  - In a retrospective study, 31 patients were identified over a period of 25 years
      as having sustained traumatic knee dislocations without associated fractures.
      Three patients had early amputation secondary to vascular complications. Ten
      popliteal artery disruptions and five peroneal nerve palsies were diagnosed. At
      the time of follow-up evaluation (average, 40 months), 16 patients were examined.
      Operatively treated patients (n = 6) tended to have better motion (129 degrees)
      than nonoperatively treated patients (108 degrees). Varus instability was seen in
      only two patients treated nonoperatively. All patients except one experienced
      persistent functional limitations. Roentgenographic follow-up examination showed
      similar degenerative changes in both groups.

PMID- 1395295
TI  - Uncemented intramedullary fixation of implants using polyethylene sleeves. A
      roentgenographic study.
AB  - Forty-three prostheses with noncemented, high-molecular-weight, polyethylene
      sleeved components were used in the treatment of bone tumors around the knee in
      growing children. The average age of the patients was 11 years. There were 27
      boys and 16 girls. There were 17 sleeved components in the distal femur and 26 in
      the proximal tibia. The average follow-up time was 27 months. The roentgenograms
      were nominally obtained at three, six, 12, 18, and 24 months, and irregularly
      thereafter, and were assessed using a zonal evaluation scheme. A sclerotic
      interface around the polyethylene sleeves invariably developed and progressed in
      density up to 28 months postoperatively. There were significant zonal differences
      in sclerosis, particularly between the plateau and the mid-sleeve zone. Only in
      one patient did a sleeve become loose and require revision.

PMID- 1395296
TI  - The cemented unicondylar knee arthroplasty. An in vitro comparison of three
      cement techniques.
AB  - Three cementation techniques were investigated to determine their effect on
      initial fixation of unicondylar tibial components. Twenty-one anatomic specimens
      were divided into three groups. In Groups A and B, the medial tibial plateau was
      minimally resected. Group A was drill interdigitated and pulse lavaged, Group B
      was left "as cut". In Group C, the articular cartilage was curetted, exposing the
      subchondral bone entirely. An Ortholoc II unicondylar prosthesis was cemented
      onto the tibias, after which a 981-N load was applied anteromedially at 1 Hz for
      10,000 cycles. Measurements for anterior and posterior micromotion were taken at
      the first cycle, every ten cycles for the first 100 cycles, every 100 cycles for
      the first 1000, and every 250 cycles thereafter. Measurements for anterior
      subsidence and posterior liftoff were taken after every 1000 cycles. Group A was
      found to be significantly better than Group B in anterior micromotion, posterior
      micromotion, and posterior liftoff in all load cycles. Group A was also found to
      be significantly better than Group C in anterior micromotion, posterior
      micromotion, and posterior liftoff in all load cycles. The performance of Groups
      B and C was highly variable. Both groups had specimens with extreme micromotions
      in response to low loads. Group A provided consistent and superior results. This
      study shows that cementation techniques employing multiple-drill-hole
      interdigitation and pulse lavage produce rigid initial fixation and consistent
      excellent results. Cementing to the smooth subchondral bone or unlavaged
      cancellous bone was unreliable.

PMID- 1395297
TI  - The management of fixed flexion contractures during total knee arthroplasty.
AB  - Fifty-one knees in 40 patients with joint surface degeneration accompanied by
      fixed flexion contractures (FFC) greater than 20 degrees were treated with total
      knee arthroplasty using a minimally constrained posterior cruciate ligament
      retaining prosthesis. Special techniques were employed in an attempt to achieve
      maximal correction at the time of surgery. The residual FFC measured 3.1 degrees
      at the completion of the arthroplasty, 10.1 degrees at three months, and 7
      degrees at two years. At 55 months postoperatively, the FFC for the
      osteoarthrotic group had improved from 25.5 degrees to 3.6 degrees, whereas the
      rheumatoid group improved from 28.7 degrees to 8.6 degrees. The average knee
      score for the osteoarthrotic group was 89 compared with 81 for the rheumatoid
      group. Knees that were left with greater residual FFC at the completion of the
      arthroplasty were found to have greater residual FFC at the latest review.

PMID- 1395299
TI  - Surgical excision of hemophilic pseudotumor of the ilium.
AB  - The iliac hemophilic pseudotumor is a rare complication of hemophilia occurring
      in 1-2% of patients with Factor VIII or Factor IX deficiency. It is frequently
      disabling and life threatening. This report presents a comparative study of
      postoperative results of two cases of hemophilic pseudotumor of ilium. One
      patient undergoing partial resection showed a favorable postoperative course,
      whereas the patient with complete resection of the pseudotumor died of
      postoperative bleeding and sepsis. Studies on the postoperative results of these
      two cases indicate that careful preoperative consideration of tumor size and
      degree of infiltration is of the utmost importance in operative management. Early
      excision of tumors eliminates the possibility of endogenous infection. Even
      partial resection of huge tumors, leaving the lateral wall intact for
      compression, can promote recovery of functions.

PMID- 1395298
TI  - Complete knee dislocation without posterior cruciate ligament disruption. A
      report of four cases and review of the literature.
AB  - Complete knee dislocation usually causes disruption of both the anterior and
      posterior cruciate ligaments. Four cases of complete knee dislocation without
      posterior cruciate ligament (PCL) disruption are reported. All cases involved
      either anterior or anteromedial dislocation with anterior cruciate ligament
      disruption and collateral ligament injury, but without posterior cruciate
      disruption. This is an uncommon finding in complete dislocation of the knee. The
      PCL may occasionally be spared significant injury in anterior type dislocations,
      however, thus favorably affecting treatment options.

PMID- 1395300
TI  - Lower-limb proprioception in above-knee amputees.
AB  - A proprioception measurement system was designed and constructed to evaluate
      lower-limb knee joint proprioception in ten above-knee amputees. The system
      permitted the testing of subjects in a position simulating late swing phase of
      gait. The threshold for detection of slow passive motion and the ability to
      reproduce specified lower-limb positions were recorded for the sound and the
      prosthetic limbs of the subjects. A significant difference was detected between
      prosthetic and sound limb passive motion detection threshold; however, no
      difference was found between prosthetic and sound limb passive motion
      reproduction. This finding suggests the importance of hip joint motion
      appreciation in the amputees' proprioception of the prosthetic knee joint when
      these motions are associated. Prosthetic limb passive motion reproduction error
      decreased with age, suggesting that the amputees may improve their ability to use
      remaining lower limb proprioceptive mechanisms to compensate for the loss of
      anatomic knee joint structures.

PMID- 1395301
TI  - Managing complications of posterior spinal instrumentation and fusion.
AB  - Complications of posterior spinal instrumentation for adolescent idiopathic
      scoliosis are often preventable. Preoperative planning helps to minimize
      intraoperative and postoperative problems. Late recurrence of rotational
      deformity (crankshaft) in skeletally immature patients can be prevented by adding
      anterior surgery. Intraoperative complications are minimized by controlled
      hypotensive anesthesia and sequencing of surgical steps to allow for
      autocoagulation, reducing blood loss. Use of spinal cord monitoring, Stagnara
      wakeup test, and careful distraction decreases the risk of neurologic deficit.
      Good hook-site preparation helps avoid dural tears. The incidence of
      postoperative pneumothorax and hemothorax is decreased by careful hook
      attachment, avoiding pleural penetration, judicious use of rib excision
      thoracoplasty, and roentgenographic verification of central venous pressure line
      position. Postoperative recommendations include bed position at 30 degrees,
      frequent log rolling, incentive spirometry, early sitting and standing, early
      Foley catheter and nasogastric tube removal, prophylactic antibiotics, and prompt
      attention to wound infections. Postoperative orthotic wear, prescribed exercise,
      and activity restriction decrease the risk of early instrumentation failure and
      help correct early postoperative trunk imbalance. The late complications include
      suspected pseudarthrosis; this should be surgically treated again if there is
      persistent pain or marked loss of curve correction.

PMID- 1395302
TI  - Force- and moment-generating capacity of lower-extremity muscles before and after
      tendon lengthening.
AB  - A computer model of the human lower extremity was developed to study how surgical
      lengthening of tendon affects the force- and moment-generating capacity of the
      muscles. This model computes the maximum isometric force and the resulting joint
      moments that each muscle-tendon complex can develop at any body position. Tendon
      lengthenings were simulated by increasing the tendon length of each muscle-tendon
      complex and computing the change in the maximum isometric muscle force and joint
      moments at a specific body position. These simulations showed that the forces and
      moments developed by the ankle plantarflexors are extremely sensitive to changes
      in tendon length. For example, at a body position corresponding to the midstance
      phase of gait, the maximum isometric moment generated by soleus decreased 30%
      with a 1-cm increase in tendon length, and 85% with a 2-cm increase in tendon
      length. In contrast, 1- and 2-cm increases in iliopsoas tendon length decreased
      its hip flexion moment by only 4% and 9%, respectively. This article quantifies
      the sensitivity of muscle force and joint moments to changes in tendon length for
      the most commonly lengthened lower-extremity tendons. These results indicate how
      much each of these tendons should be lengthened to achieve an incremental
      decrease in muscle force or joint moment.

PMID- 1395303
TI  - Holding power and reinforcement of cancellous screws in human bone.
AB  - The authors report an in vitro biomechanical evaluation of a biodegradable
      material that might be used for the reinforcement of surgical screws in fractures
      involving severely osteoporotic bone. The material is a particulate composite
      with a matrix phase consisting of a hydrolyzable prepolymer, polypropylene
      fumarate (PPF), crosslinked with methacrylate monomer, and a particulate phase
      consisting of tricalcium phosphate and calcium carbonate. Pullout force and
      stripping load of cancellous screws were determined along with screw pullout
      force before and after reinforcement with either polymethylmethacrylate (PMMA) or
      PPF composite. Pullout force was moderately correlated (R2 = 0.59) with apparent
      density by a power law relationship of the form 0.065p1.37-1.77. Stripping load
      was strongly correlated (R2 = 0.91) with apparent density by a power law of the
      form 0.13p1.35-93.8. Mean pullout force before and after reinforcement with PMMA
      was 382 +/- 100 N (mean +/- standard deviation) and 879 +/- 315 N, respectively.
      Mean pullout force before and after reinforcement with PPF composite was 571 +/-
      294 N and 829 +/- 354 N, respectively. Although the increase in pullout force
      with cement reinforcement was highly significant in both cases, the magnitude of
      the increase did not depend on the type of cement. Thus PPF seems to provide
      reinforcement that is equivalent to that provided by PMMA.

PMID- 1395304
TI  - A reproducible porcine vertebral fracture for biomechanical testing of spinal
      fixation devices.
AB  - To evaluate vertebral fracture fixation devices in the laboratory, it is
      necessary to produce identical and unstable fractures either in anatomic specimen
      or animal models. Consistent achievement of this goal has not been reported in
      the literature. This report presents a technique for the study of reproducibility
      for a particular vertebral fracture model. A precise anterior defect was created
      in a vertebra of each specimen drawn from a homogeneous population of mature sow
      spines. The spines were loaded to failure. Fracture reproducibility was shown by
      measurement of load and displacement, and confirmed by roentgenographic
      evaluation. The technique is easily applied to human specimens. Because there is
      a plethora of fracture fixation devices based on hooks, wires, or, more recently,
      plates and pedicle screws, the reliability of comparative testing of these
      devices in the laboratory requires an appropriate and reproducible fracture.

PMID- 1395305
TI  - Rapidly destructive arthropathy of the hip. Studies on bone resorptive factors in
      joint fluid with a theory of pathogenesis.
AB  - The mechanism of joint destruction in rapidly destructive coxopathy was studied
      by analyzing bone resorptive factors in the joint fluid. Prostaglandins were
      found to play a partial role in joint destruction. Some cases of rapidly
      destructive coxopathy revealed elevated levels of interleukin-1 beta (IL-1 beta)
      in the joint fluid. Electrophoretic analysis of proteolytic enzymes in
      polyacrylamide gel containing sodium dodecyl sulfate and copolymerized gelatin
      demonstrated that the resorptively active peptides have relative molecular
      weights (M(r)) of approximately 92,000, 72,000, and lower than 60,000. Cultured
      cells from synovia obtained perioperatively secreted matrix metalloproteinase 2
      (MMP-2) with an M(r) of 72,000 and matrix metalloproteinase 3(MMP-3) with an M(r)
      of 57,000. Synovial cells from the patients with coxarthrosis secreted fewer
      proteolytic enzymes. Prostaglandins, IL-1 beta, MMP-2, and MMP-3 could act
      synergetically as promotors in the rapid destruction of the hip joint.

PMID- 1395306
TI  - Prostaglandin E2 production by the membrane surrounding loose and fixated
      cemented tibial hemiarthroplasties in the rabbit knee.
AB  - Sixteen mature New Zealand female rabbits had cemented, tibial hemiarthroplasty
      of the right knee (correction of hip) using a stemmed, fluted, titanium-alloyed,
      condylar type prosthesis. In the fixated prosthetic group (eight rabbits), a 1.5
      cm3 doughy bolus of polymethylmethacrylate (PMMA) was used to cement the
      prosthesis firmly. In the loose group (eight rabbits), the cement was allowed to
      cure ex vivo on the implant; the prosthesis was then implanted and rotated to
      ensure that it was loose fitting. Roentgenograms performed postoperatively and at
      three months were graded for new lucent lines. The implant area was harvested
      aseptically and cultured during a three-day period, and the cumulative collection
      of tissue culture supernatants was assayed for prostaglandin E2 (PGE2). The mean
      cumulative grading of new lucent lines was 0.4 +/- 0.2 (mean +/- SEM) for the
      fixated prosthetic group and 2.3 +/- 0.5 for the loose prosthetic group.
      Specimens from the nonloose group produced 8.85 +/- 1.44 ng of PGE2 on the right
      prosthetic side, and 17.29 +/- 3.72 ng of PGE2 on the left, nonimplanted side.
      Specimens from the loose prosthesis group produced 52.35 +/- 16.28 ng of PGE2 on
      the right prosthetic side and 17.29 +/- 3.72 ng of PGE2 on the left, nonimplanted
      side. Increased PGE2 production relative to fixated prostheses was noted in the
      membranes surrounding loose prostheses. The left, nonimplanted sides were not
      statistically different. Roentgenographic and biochemical evidence indicates that
      a cemented tibial hemiarthroplasty implanted in the rabbit knee can provide a
      short-term model of arthroplasty loosening.

PMID- 1395307
TI  - Effects of cyclosporin A on experimental new bone formation in rats.
AB  - The effects of the immunosuppressive drug cyclosporin A (CsA) on bone induction
      by demineralized allogeneic (rat) bone matrix (DABM) and demineralized xenogeneic
      (rabbit) bone matrix (DXBM) were studied. Growing rats were implanted with three
      samples each of DABM and DXBM. Groups of eight rats were treated with 0.5 or 2 mg
      CsA/kg body weight for four weeks and compared with a placebo group. Cyclosporin
      A treatment enhanced bone induction in DABM implants by 40 to 50% at four weeks,
      whereas there was no difference from the control group at eight weeks.
      Demineralized xenogeneic bone matrix induced virtually no bone in control rats at
      four weeks, whereas the net bone formation increased four to five times in both
      groups of CsA-treated rats. At eight weeks, DXBM without CsA had induced some
      bone formation, and the amount was almost equal to that of DABM implants in CsA
      treated groups. Also, the mineral accretion rates of DXBM were equal to DABM
      implants in CsA-treated rats. Cyclosporin A treatment doubled the uptake of 45Ca
      in the orthotopic skeleton (femora) at four weeks without affecting the mineral
      content, indicating an increased mineral turnover. Immunologic reactions may
      inhibit bone induction by DXBM, which can be counteracted by treatment with CsA.

PMID- 1395308
TI  - Biomechanical comparisons of unidirectional and bidirectional Kirschner-wire
      insertion.
AB  - Peak axial loads on entry and peak pull-out loads were measured for Kirschner
      wires (K-wire) inserted into canine metacarpals. The wires were placed using a
      standard, unidirectional drill and using an oscillating, bidirectional drill that
      reversed spin direction every 120 degrees. Seven trocar-tip wires were compared
      with seven diamond-tip wires using each drilling method. The trocar-tip wires
      demonstrated equal peak axial loads on entry when drilled at comparable speeds
      unidirectionally and bidirectionally. Pull-out load of the trocar tip after
      bidirectional insertion was less than that for unidirectional insertion but was
      still in the clinically useful range. The diamond-tip wire exhibited higher peak
      axial load on entry and lower peak pull-out load when drilled bidirectionally.
      Bidirectional insertion of a trocar-tip K-wire offers fixation characteristics
      comparable with those with unidirectional insertion and will potentially reduce
      the risk of soft-tissue damage associated with winding-up and avulsion of vital
      structures on the spinning shaft of a unidirectional driver.

PMID- 1395309
TI  - The nature of pseudoarthrosis. 1968.

PMID- 1395310
TI  - In vitro elution characteristics of commercially and noncommercially prepared
      antibiotic PMMA beads.
AB  - The successful treatment of osteomyelitis with commercially prepared gentamicin
      polymethylmethacrylate (PMMA) (Septopal) beads and surgical debridement has led
      to the use of this technique in the United States. However, commercially prepared
      gentamicin-PMMA beads are not currently available to orthopedic surgeons in the
      United States. Therefore, these surgeons commonly manufacture their own
      antibiotic-containing cement beads in the operating room at the time of surgery.
      There is little data that compare the antibiotic elution characteristics of such
      preparations to commercially prepared gentamicin-PMMA beads. This study compares
      the measured amount of antibiotic elution of either gentamicin or tobramycin from
      laboratory manufactured Zimmer, Simplex, or Palacos beads to commercially
      prepared gentamicin-PMMA (Septopal) beads. During a 30-day study period,
      commercially prepared gentamicin-PMMA beads eluted more total antibiotic and
      maintain higher concentrations than did antibiotic acrylic composites
      manufactured in the authors' laboratory.

PMID- 1395311
TI  - Roentgenographic scoring system for evaluating success of femoral hip implants.

PMID- 1395312
TI  - Anatomic and technical considerations of pedicle screw fixation.
AB  - Pedicle screw systems provide significant and, in many cases, improved and
      previously unattainable spinal fixation. However, pedicle screw systems represent
      difficult surgical techniques involving several potential problems and
      complications. Only by detailed knowledge of the anatomy of the spine, with a
      clear understanding of the pedicle screw systems implementation, can the risks of
      complications be minimized.

PMID- 1395313
TI  - Anterior lumbar interbody fusion surgical complications.
AB  - Complications of anterior lumbar fusion may be divided into several categories.
      The first of these is complications related to patient selection, the second is
      visceral complications, and the third is vascular complications. Complications of
      anterior lumbar fusion and complications of interbody fusion technique occur at
      the graft site and the donor site.

PMID- 1395314
TI  - Complications of anterior intervertebral grafting.
AB  - Reconstruction of the spine after anterior decompression is essential to restore
      stability and function. A variety of materials and methods are available to
      reconstitute the vertebral column. Numerous complications of anterior grafting
      have been identified, and include failure of the graft, graft extrusion,
      nonunion, and infection. The clinical severity of these complications vary. The
      use of spinal instrumentation has helped to address some of these problems.
      Although certain problems are the result of faulty decision making or technical
      error, others are related to the severity of the patient's disease and the
      limitations of grafting materials. Some complications can be avoided while others
      can be anticipated and perhaps corrected early.

PMID- 1395315
TI  - Complications of chemonucleolysis.
AB  - Complications in chemonucleolysis are inevitable. However, the incidence of these
      may be minimized with attention to detail. Proper patient selection, based on a
      knowledge of the natural history of lumbar disk herniation and elimination of
      patients with contraindications to diskolysis, will result in a higher success
      rate with lower incidence of complications in diskolysis. Once the proper patient
      has been selected, attention must be turned to technique with respect to the use
      of local anesthesia, appropriate patient positioning, good fluoroscopic control,
      and two-needle technique for appropriate needle positioning. Immunologic
      complications can be nearly eliminated with the use of a preoperative enzyme
      immunoassay test. Carefully considering all of these factors will allow
      chemonucleolysis to present a safe alternative to disk surgery.

PMID- 1395316
TI  - Percutaneous diskectomy.
AB  - Automated percutaneous diskectomy and manual percutaneous diskectomy (PCD) have
      gained recent popularity as alternatives to traditional surgical diskectomy or
      microdiskectomy. Initial reports of morbidity seem low. The rates of infection,
      and neurologic and vascular complications appear comparable or less than the
      morbidity associated with surgical diskectomy or microdiskectomy. However,
      inconsistent reports of the efficacy of PCD may cause more concern about overuse
      than about the morbidity.

PMID- 1395317
TI  - Pseudarthrosis of the spine.
AB  - Pseudarthrosis remains the leading cause of failed spinal fusions. The common
      causes of this complication are inadequate surgical technique, excessive stresses
      across the fusion site, insufficient internal or external stabilization, and
      unrecognized metabolic abnormalities. Many radiologic techniques have been used
      to diagnose pseudarthrosis in the spine. Nonetheless, the diagnosis of a nonunion
      as well as the ability to correlate the nonunion with the patient's clinical
      symptoms remains a challenge. In treating a symptomatic pseudarthrosis, the
      surgeon should first attempt to identify those factors that contributed to the
      development of a nonunion. The approach can then either be exploration of the
      fusion mass with regrafting of the pseudarthrosis or extending a fusion to
      locations within the abnormal segment of spinal motion.

PMID- 1395318
TI  - Disk herniations associated with compression instrumentation of lumbar flexion
      distraction injuries.
AB  - Flexion-distraction injuries are often treated by open reduction and fusion using
      compression instrumentation. Three cases that were complicated by disk herniation
      at the injured level, with an acquired neurologic deficit, are reported. Middle
      column failure through the annulus fibrosis (Gertzbein and Court-Brown Type A)
      appeared to be a common feature. This may be a permissive condition for this
      complication as compression is applied across the torn annulus. Preoperative
      magnetic resonance imaging and postreduction myelography may identify such
      herniations. Acquired neurologic deficits after reduction and instrumentation
      demand emergent evaluation and treatment.

PMID- 1395319
TI  - Postoperative posterior spinal wound infections.
AB  - The incidence of postoperative spinal infections increases with the complexity of
      the procedure. Diskectomy is associated with less than a 1% risk of infection;
      spinal fusion without instrumentation is associated with a 1%-5% risk; and fusion
      with instrumentation may be associated with a risk of 6% or more. Twenty-two
      postoperative posterior spinal infections that occurred during a three-year
      period were reviewed for this report. Staphylococcus aureus was the most frequent
      organism cultured (more than 50% of the cases). Other recurring organisms were
      Staphylococcus epidermis, Peptococcus, Enterobacter cloacae, and Bacteroides.
      Many patients had multiple organisms. Risk factors appeared to include advanced
      age, prolonged hospital bed rest, obesity, diabetes, immunosuppression, and
      infection at remote sites. Operative factors included prolonged surgery (greater
      than five hours), high volume of personnel moving through the operating room, and
      instrumentation. Postoperative contamination may occur and may be related to
      prolonged postoperative bed rest, skin maceration (thoracolumbosacral orthoses),
      and drainage tubes exiting distally from lumbar wounds (toward the rectum).
      Effective treatment includes early diagnosis, surgical debridement and
      irrigation, and parenteral antibiotics. Superficial infections were treated
      successfully with wound closure over outflow tubes, and deep infections with
      inflow-outflow systems. Maintaining the instrumentation in place was possible in
      most cases. Parenteral antibiotics were maintained for six weeks in every case.

PMID- 1395320
TI  - [Adult GM1 gangliosidosis--biochemical studies--1].
AB  - To address the pathogenesis of GM1 gangliosidosis, especially adult form,
      intracellular signal transduction pathway of EGF in skin fibroblasts from
      patients with this disorder was examined. For this purpose, skin fibroblasts from
      2 different patients with adult form of the disorder and from 4 different normal
      controls were used. The results showed that 1) EGF-receptor autophosphorylation
      was diminished in skin fibroblasts from patients with altered time course of
      phosphorylation-dephosphorylation reaction. 2) The amount of EGF-receptor protein
      was decreased in cells from patients compared with that of controls. 3) 125I-EGF
      binding + internalization studies revealed decreased rate of EGF binding and
      internalization in patient cells. 4) Ribosomal S6 protein phosphorylation was
      strongly enhanced in naive cells from patients, but the reactivity to EGF was
      diminished compared with control cells. These data strongly suggest that patient
      fibroblasts have abnormalities in the intracellular signal transduction pathway
      of EGF. This paper is considered to be the first report demonstrating
      abnormalities in EGF-signal transducing system in human disorders.

PMID- 1395321
TI  - [The corticospinal tract of amyotrophic lateral sclerosis--a morphometric
      analysis of the myelinated fibers].
AB  - The myelinated fibers in the lateral corticospinal tract at the C6, T7, L4 levels
      in amyotrophic lateral sclerosis (ALS) and control cases were morphometrically
      examined. ALS cases consisted of 6 males and 2 females with ages ranging between
      48 and 85 years, and were all the common or bulbar form in clinical
      manifestation. As for controls, 10 cases who died of non-neurological diseases,
      with age ranging 36 to 90 years were served. The population and the diameter
      profile of the myelinated fibers in the corticospinal tract of the C6, T7, L4
      levels were measured by the method previously described and expressed as number
      per mm2. In control subjects, fiber-size histograms of myelinated fibers showed a
      bimodal pattern with a sharp peak of small fibers (less than 7.28 microns) and a
      broad peak of large fibers (greater than or equal to 7.28 microns) in all the
      spinal levels. In ALS cases, large myelinated fibers were predominantly
      diminished in number, a small myelinated fibers were also decreased in some
      cases. The degree of fiber loss was extremely variable among cases; well
      populated in large fibers in some cases. As for the rostral caudal distribution
      of myelinated fiber loss, a caudally-accentuated fiber loss particularly in large
      fiber was seen in some of the cases. The topographical distribution of fiber loss
      in the horizontal plane of the corticospinal tract in ALS did not show a
      distinctive pattern.

PMID- 1395323
TI  - [Transcranial magnetic stimulation of the facial nerve].
AB  - It was the object of the present study to determine whether transcranial facial
      nerve stimulation using a magnetic coil can be clinically applicable, and to find
      the site where the facial nerve is best stimulated. A magnetic coil was placed
      over the parieto-occipital skull of the subjects for stimulation, and the facial
      nerve was electrically stimulated in its intracranial and peripheral courses.
      Then an electromyogram was recorded from the nasalis muscle of the face on the
      stimulated side. In 9 healthy volunteers, 18 facial nerves received magnetic and
      electric stimuli in the peripheral region, and the actual site of stimulation was
      estimated from the conduction velocity of the nerve. The conduction velocity was
      56.6 +/- 4.8 m/s, and the latency between CMAPs for electric at the magnetic
      stimuli to the posterior tragus was 1.23 +/- 0.21 ms. Therefore, the position
      stimulated by magnetic coil was estimated to be 70.0 +/- 11.4 mm central to the
      posterior tragus, i.e., near the root exit zone. In two patients undergoing
      surgery in the cerebellopontine angle, transcranial magnetic stimulation and
      electrical stimulation of the intracranial facial nerve were compared
      intraoperatively. The CMAP produced by transcranial magnetic stimulation
      coincided closely with that produced by direct electrical stimulation of the root
      exit zone. Thus, the facial nerve was stimulated at the root exit zone, and this
      method could be expected to be useful for evaluation of disorders of the
      intracranial facial nerve.

PMID- 1395322
TI  - [The effect of anticholinergic drugs on 123I-IMP SPECT in Parkinson's disease].
AB  - Several reports have suggested that anticholinergics have some associations with
      mental deterioration in Parkinson's disease (PD). We investigated the effect of
      anticholinergics on regional cerebral uptake of tracer in PD patients using N
      isopropyl p-[I-123] iodoamphetamine SPECT. Sixteen pairs of region of interest
      (ROI) were located in the cortex, a pair in the basal ganglia, thalamus, and
      cerebellum. The size of each ROI was about 16 mm x 16 mm. Regional cerebral
      uptake ratio (rCUR) was calculated by the next equation: rCUR = (total count in
      an ORI)/(mean of total count in the cerebellar ROIs). The comparison consisted of
      two parts; (1) 7 PD patients (age 59-76 (65.4 +/- 6.7 mean +/- S.D.)) who had
      been on chronic anticholinergic therapy underwent SPECT and Wechsler Adult
      Intelligence Scale (WAIS) twice, for the first time when they were on
      anticholinergics and second a month after discontinuation of anticholinergics.
      All but two patients performed significantly better on WAIS after discontinuation
      than when they were on anticholinergics. The improvement was about 10 points in
      total IQ. (2) 11 PD patients (age 52-79 (64.5 +/- 8.6 mean +/- S.D.)) on chronic
      anticholinergic therapy including all but two patients mentioned above (group A)
      and 25 PD patients (age 52-88 (66.7 +/- 9.8 mean +/- S.D.)) not receiving
      anticholinergics (group B) also underwent SEPCT. In the comparison (1), at all
      but two ROIs was the mean rCUR higher after discontinuation than when they were
      on anticholinergics and the difference was significant at 10 ROIs out of 32 ROIs
      in the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395324
TI  - [Cerebrospinal fluid levels of 28 kDa calcium-binding protein in patients with
      neurological diseases].
AB  - Vitamin D-dependent calcium-binding protein (Calbindin-D: CaBP) (MW 28 kDa) is
      present in high concentrations in the central nervous system (CNS), especially in
      the cerebellum. In the cerebellum, CaBP is localized in Purkinje cells. By using
      an enzyme immunoassay method, we measured the cerebrospinal fluid (CSF) levels of
      CaBP in 96 neurological patients and 24 control subjects, and evaluated the
      clinical usefulness of determining CaBP, especially in the diagnosis of
      cerebellar damage. CSF CaBP levels were strikingly elevated in patients with
      cerebellar lesions, including primary spinocerebellar degeneration (SCD),
      subacute cerebellar degeneration with lung cancer, Wernicke-Korsakoff syndrome,
      as well as in patients with cerebrovascular disease (CVD) without involvement of
      the cerebellum. In these 2 groups, neuron-specific enolase (NSE) levels were
      determined. The ratio of CaBP to NSE (CaBP/NSE) in patients with cerebellar
      lesions was higher than that in CVD, reflecting differences in lesions between
      these 2 groups. In the SCD group, multiple system atrophy (MSA) showed higher
      CaBP levels than the other types of SCD. Probably it reflects remarkable damage
      of the Purkinje cells in MSA. In MSA, the CaBP levels decreased with the duration
      of illness. In myelopathy, neuropathy, meningitis, multiple sclerosis, and other
      degenerative diseases, the increase of CaBP was not remarkable. Our results
      suggested that CSF CaBP is considered to be a marker of cerebellar damage.

PMID- 1395325
TI  - [A multivariate analysis of prognostic factors of spinocerebellar degenerations].
AB  - To clarify the factors relating to the prognosis of spinocerebellar degenerations
      (SCD), we performed a follow-up study on the survival of patients with Friedreich
      disease, familial spastic paraparasis, sporadic olivopontocerebellar atrophy
      (OPCA), hereditary OPCA of Menzel type, sporadic late cortical cerebellar atrophy
      (LCCA), cerebellar atrophy of Holmes type, Shy-Drager syndrome, striatonigral
      degeneration, dentatorubropallidoluysian atrophy, or Joseph disease. One hundred
      and forty-eight patients admitted to the Nagoya University Hospital during the
      period of 1976 to 1990 were dealt with. They had been followed-up for 15 years at
      longest through the medical records, or through the direct informations from the
      patients or their family members or both. In order to find factors influencing
      the survival of the patients, Kaplan-Meier method was used as the 1st step to
      construct the survival curve for each factor. These were calculated by
      generalized Wilcoxon test. Employing Cox's proportional hazard model, a
      multivariate analysis was then performed based on the factors which were shown
      significant in the 1st step. The multivariate analysis showed that the following
      four factors are related to the prognosis of SCD patients, i.e., lack of
      hereditary trait, existence of orthostatic hypotension, lack of walking disorder
      at onset, and lack of nystagmus on admission. Of these factors, the lack of
      hereditary trait had the most intimate relation to their poor prognosis.
      Therefore, these four factors are statistically informative to predict prognosis
      of each patient with SCD.

PMID- 1395326
TI  - [A case of SSPE presenting visual disturbance and serial MRI study].
AB  - A case of subacute sclerosing panencephalitis (SSPE) was reported. The patient
      was a 16-year-old boy and he initially developed visual disturbance. His
      neurologic symptoms were myoclonus, dementia, and visual disturbance which was
      rare as an initial symptom in SSPE. Fundoscopy revealed bilateral pole
      chorioretinitis and macular degeneration. Serial MRI study demonstrated the
      lesions in the brain and right eye ball. The distribution varied as time went on.
      T2-weighted MR images showed the lesions more clearly than T1-weighted MR images.
      In this case dementia was marked but the lesions in the cerebrum on the MR images
      were considerably smaller than expected. Although MR image is useful to show the
      lesions, the discrepancy between clinical signs and MR images may be present in
      the early stage in SSPE.

PMID- 1395327
TI  - [Two familial cases with exertion-induced heat stroke--relationship to malignant
      hyperthermia].
AB  - Two patients in a family of exertion-induced heat stroke were reported. Case 1: A
      23-year-old male, paternal cousin of case 2, was admitted to our hospital because
      of loss of consciousness during running under a burning sun. On physical and
      neurological examinations, he was deeply comatose with high fever, tachycardia,
      and increased deep tendon reflexes. Laboratory findings disclosed rhabdomyolysis,
      acute renal failure, disseminated intravascular coagulation, liver injury, and
      brain edema. He recovered after intensive cooling, some antibiotics, glycerol and
      sodium dantrolene administration. Case 2: A 19-year-old male experienced loss of
      consciousness and high fever during playing soccer at 15 years of age, and was
      admitted to a hospital. On admission, he had high fever of 38.7 degrees C, and
      increased serum CK level. He recovered two weeks after admission. He was
      readmitted to our hospital to evaluate the predisposition for malignant
      hyperthermia. His physical and neurological examinations showed no abnormalities.
      Routine laboratory findings were within normal limits. Muscle biopsy findings of
      cases 1 and 2 were mildly increased number of fibers with centrally placed
      nuclei. Caffeine test on skinned muscle fibers from the biopsies showed normal
      response in both type 1 and 2 fibers. The present patients were diagnosed as
      having exertion-induced heat stroke, but with no increased muscle fiber
      sensitivity to caffeine, suggesting that the pathomechanism differs from that of
      malignant hyperthermia induced by malfunction of sarcoplasmic reticulum.

PMID- 1395328
TI  - [Gadolinium-MRI findings of two adrenoleukodystrophy cases treated with gamma
      globulin].
AB  - Two cases of adrenoleukodystrophy were reported. We treated them with intravenous
      gamma-globulin infusion. MRI with gadolinium enhancement was performed before and
      after the therapy to evaluate the effect of gamma-globulin. Case 1 was a 19-year
      old boy, who noticed left hemianopsia when he was 18 years old. Case 2 was a 36
      year-old man, who developed ataxic gait and character change when he was 33 years
      old. Very long chain fatty acids in plasma and RBC membrane were elevated in both
      cases. On T2-weighted image of MRI, high signal lesions were seen in the white
      matter of occipital lobe in case 1, cerebellum, internal capsule, and around the
      corpus callosum in case 2. On T1-weighted image, the rim of every lesion was
      enhanced by gadolinium infusion. After the gamma-globulin therapy, gadolinium
      enhancement of the rim remarkably reduced in case 1. No reduction was observed in
      case 2. MRI findings of case 1 indicate the possibility that gamma-globulin may
      suppress the inflammation of the adrenoleukodystrophy.

PMID- 1395329
TI  - [A case of chronic toluene intoxication with atrophy of cerebrum, cerebellum and
      brainstem on CT and MRI].
AB  - A 28-year-old man developed neurological disorders consisting of cerebellar
      symptoms and dementia over a period of 8 years of inhalation of toluene. He also
      developed bilateral optic atrophy. CT scan and MRI revealed atrophy of cerebrum,
      cerebellum and brainstem. The severity of neurological symptoms corresponded with
      the findings of CT and MRI. Furthermore, MRI (T2) showed reduced signal intensity
      in bilateral thalamus. This patient was also admitted to another hospital 2.5
      years ago. Compared with the previous findings, present examinations showed
      significant progress of the atrophy of cerebrum and brainstem. It was suggested
      from the results of ABR that the disturbance of the brainstem was aggravated
      through this period.

PMID- 1395330
TI  - [A case of topographical disturbance following a left medial parieto-occipital
      lobe infarction].
AB  - A 59-year-old man was admitted to our hospital for his sudden-onset right
      hemianopsia. Thirty days after the onset, neuropsychological examination revealed
      obvious topographical disorientation and mild optic ataxia. Magnetic resonance
      imaging showed abnormal intensity area at the left medial parietooccipital region
      and left splenium of the corpus callosum. Although single photon emission CT
      showed uptake decrement in the left hemisphere, almost normal uptake was observed
      in the right hemisphere. He could recognize landmarks, but fail to recognize the
      relative position of landmarks. Therefore, his topographical disorientation was
      considered to be due to perceptual disturbance, memory disturbance of relative
      position of landmarks, or both. He was right-handed with no sinistral relative,
      and showed dyslexia and dysgraphia early in his clinical course. The laterality
      index of the dichotic listening test revealed the right ear dominance. These
      results indicated that his left hemisphere was language dominant. His
      topographical disorientation could be caused by the medial parieto-occipital
      lesion in the dominant hemisphere.

PMID- 1395331
TI  - [Wallenberg's syndrome due to vertebral artery dissection following minimal neck
      injury--report of two cases].
AB  - We described two cases of the lateral medullary syndrome (Wallenberg's syndrome)
      due to vertebral artery dissection following minimal neck injuries. The first
      case was a 45-year-old man, who hit his head and often rotated his head because
      of posterior neck discomfort. Two years after the injury, he suffered from sudden
      sharp neck pain, nausea, and vertigo, which was followed by left hand numbness
      and difficulty in walking due to the right lateral medullary syndrome.
      Angiography showed right vertebral artery dissection at the fourth segment. The
      second case, a 48-year-old man, suffered from neck pain immediately after he
      hyperextended his neck for painting a wall. Within several hours, he experienced
      left hand numbness and difficulty in walking due to the lateral medullary
      syndrome. Angiography showed a saccular aneurysm and dissection of the right
      vertebral artery at the fourth segment. In both cases, minor traumas were thought
      to be the causes of vertebral artery dissection. We surveyed previously reported
      84 cases (men: 50, women: 34) of the vertebral artery dissection due to minor
      traumas. Seventy per cent of patients were in their third or fourth decade of
      life. The main causes of trauma preceding the dissection were neck manipulation
      especially chiropractics (52%). The third segment was most vulnerable. Delay in
      onset following neck trauma could be more than a week, but in most cases the
      delay was less than 24 hours. Cervical rotation and extension were thought to
      precipitate dissection.

PMID- 1395332
TI  - [Spastic paraparesis and sensory disturbance improved by prednisolone therapy].
AB  - We reported a 65-year-old man whose sister was suffering from HTLV-I-associated
      myelopathy (HAM) and who presented slowly progressive spastic paraparesis,
      sensory disturbance in the feet, tremors and cerebellar ataxia. He was also
      positive for serum anti-HTLV-I antibody. He first showed a head tremor at the age
      of 3 years. He developed a spastic and ataxic gait when aged 15 years, and it
      became difficult for him to walk at the age of 50 years. Examination at 65 years
      showed a spastic and ataxic gait and scanning speech. Hyper-reflexia and
      Bahinski's signs were observed. Sensation in the feet was decreased. The anti
      HTLV-I antibody titer in the serum was 1:512 by the PA method, and Western blot
      analysis revealed bands of P19, P24, P28 and P32. Examination of the
      cerebrospinal fluid (CSF), including oligoclonal bands, gave normal results. The
      CSF was negative for anti-HTLV-I antibody. CT and MRI of the head showed
      cerebellar atrophy. His sister was 60 years old. She had developed a spastic gait
      at the age of 15 years. Sensory defects and bladder dysfunction developed when
      aged 35 years. Hyper-reflexia, Babinski's sign and foot clonus were observed.
      Sensation in the feet was decreased. The urinary residual volume was increased.
      Ataxia was not observed. The anti-HTLV-I antibody titer in the serum was 1:8,192
      by the PA method, and Western blot analysis revealed bands of p24, p28 and p32.
      Examination of the CSF, including oligoclonal bands, gave only normal
      results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395333
TI  - [Acute hepatitis A (HA) presenting findings of meningoencephalitis].
AB  - A 39-year-old man, who had high grade fever and headache for 4 days was admitted
      to our hospital because of generalized seizure and disturbance of consciousness.
      He was pyrexial, but not icteric. Neurological examination revealed
      disorientation, nuchal rigidity and bilateral Babinski reflexes. Laboratory test
      results included the following: GOT 1,740 U/l, GPT 2,800 U/l, bilirubin 1.2
      mg/dl, serum IgM-HA antibody cut-off index 6.8. CSF was clear, with 10
      leukocytes/mm3 and protein level of 108 mg/dl. Head CT and MRI revealed no
      abnormality. An EEG demonstrated diffuse slowing. During the following 2 days, he
      had increased obtundation and labored breathing. In the second week of
      hospitalization his neurological conditions and liver function test results
      improved. A diagnosis of HA was confirmed by a finding of serum IgM-HA antibody.
      The neurological findings, CSF findings and clinical course indicated acute
      meningoencephalitis in association with HA. To our knowledge, there have been
      only 4 previous case reports of meningoencephalitis associated with serologically
      confirmed HA infection. HA virus infection might pass unnoticed, as many cases of
      HA infection remain anicteric or subclinical. Therefore, HA virus should also be
      considered as one of the etiological agents in meningoencephalitis.

PMID- 1395334
TI  - [A case of Nasu-Hakola's disease with T2-weighted MRI finding of reduced signal
      intensity in the thalamus and putamen].
AB  - A 30-year-old female received a head injury at the age of 22 years. Subsequently
      neurological and psychiatric symptoms, such as personality change, urinary
      incontinence, dementia and gait disturbance developed. On admission, her
      cognitive function was severely impaired. Brain CT disclosed cerebral atrophy,
      dilatation of the lateral ventricle and calcification of the basal ganglia.
      Pathologically membranous structures were recognized in bone marrow. On the basis
      of these clinical findings, a diagnosis of Nasu-Hakola's disease was made. In
      this case, a T2-weighted MRI finding of reduced signal intensity in the thalamus
      and putamen was characteristic. This finding may be related to intracranial
      calcification.

PMID- 1395335
TI  - [Involvement of the ventral horn cells in Guillain-Barre syndrome and chronic
      inflammatory demyelinating polyradiculoneuritis].
AB  - The lumbar ventral horn cells and myelinated fibers in the ventral spinal roots
      of Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating
      polyradiculoneuritis (CIDP) were morphometrically analyzed. In all six cases,
      central chromatolytic changes in the ventral horn cells were commonly observed.
      In addition, two out of four GBS cases and one of two CIDP cases showed a
      significant reduction in the ventral horn cell population, particularly in
      neurons with a large diameter. The cases with significant motoneuron loss also
      showed a remarkable reduction in the number of myelinated fibers in the ventral
      spinal roots, and severe axonal degeneration was observed in cases in acute
      phase. Astrogliosis of the ventral horn was also seen in some cases. The present
      study suggested that motoneuron loss in the primary demyelinating diseases like
      GBS and CIDP is the consequence of the axonal pathology of the motoneuron axons.
      These observations are helpful to understand motoneuron loss in certain
      motoneuron diseases with preferential involvement of lower motor neurons.

PMID- 1395336
TI  - [Varicella-zoster virus-associated spinal myoclonus without skin lesions].
AB  - A 50-year-old woman was admitted to our hospital because of abnormal involuntary
      movement of upper abdomen. Three months before admission, she had suffered from
      left lateral chest pain without skin lesions for one week. The neurological
      examination on admission revealed myoclonus of upper abdomen, and hyperalgesia
      and thermohyperesthesia from T4 to T9. There was no weakness, the tendon reflexes
      were symmetrical and the plantar responses were flexor. The surface EMG disclosed
      the symmetrical, synchronous contractions of m. rectus abdominis and m. obliques
      externus abdominis. This spinal myoclonus reduced during sleep. The EEG, CT and
      MRI showed no abnormalities. Serum varicella-zoster virus (VZV) titers increased
      significantly on follow-up examinations. Clonazepam, 1.5 mg daily was effective
      in this patient. The myoclonus spontaneously disappeared without clonazepam in
      six weeks after onset, and at the same time the sensory disturbance also
      improved. From the neurological findings and clinical course, we consider this
      spinal myoclonus was probably elicited by involvement of the inhibitory
      interneurons of the dorsal horns, due to immune response to latent VZV infection
      but not to direct neuronal destruction by VZV. Spinal myoclonus should be
      recognized as the spectrum of neurological disease associated with VZV even in
      the absence of skin lesions.

PMID- 1395337
TI  - [Unilateral persistent hyperhidrosis after ischemic stroke].
AB  - A 64-year-old right hemiplegic woman, who had been treated for hypertension for
      15 years, was admitted to our hospital. Neurologic examination on admission
      disclosed right hemiplegia and motor aphasia; however, ophthalmoparesis,
      pupillary abnormality, and blepharoptosis were not evident. Excessive sweating on
      the right side of the body, which was most marked on the face, was observed.
      Amount of sweating on the left side of the body was normal. Unilateral
      hyperhidrosis persisted for more than 2 months. MRI revealed hemorrhagic
      infarctions in the left basal ganglia, internal capsule, thalamus, hypothalamus,
      and medial part of the cerebral peduncle. 123I-IMP SPECT disclosed hypoperfusion
      in the left striatum, thalamus, occipital cortex, and right cerebellar
      hemisphere. Cerebral angiography revealed arteriosclerotic changes in the basilar
      artery, but that the left posterior cerebral artery and its branches were not
      occluded. Unilateral persistent hyperhidrosis is rare after ischemic stroke.
      Hypothalamic lesion was thought to be responsible for the hyperhidrosis in this
      patient. As the hypothalamus receives its blood supply from the posterior
      cerebral artery, unilateral persistent hyperhidrosis may be an important sign of
      cerebral infarction in the posterior cerebral artery region.

PMID- 1395338
TI  - [A case of giant pigmented nevus with multiple meningiomas].
AB  - A 36-year-old female had a giant congenital pigmented nevus on her anterior
      trunk. She complained of muscle weakness of the right arm and leg in August 1988,
      and she was admitted to our hospital to take medical examinations in September
      1988. Neurological examination revealed right hemiparesis and exaggerated deep
      tendon reflexes. Three small falx meningiomas were shown on CT scans and MR
      images, but they did not appear to be causes of her symptoms. CT-myelography and
      MR images revealed an intradural extramedullary tumor spreading from the foramen
      magnum to C2. Oncotomy and C1 laminectomy were performed. Histological finding
      was compatible with transitional meningioma. Neurological symptoms markedly
      improved after operation. This patient is considered as a case of neurocutaneous
      syndrome with central nervous system tumors. Considering that both giant
      pigmented nevus and meningioma originate from neural crest, they appear to be
      closely related each other. Such a combination of giant pigmented nevus and
      meningioma has not yet been reported.

PMID- 1395339
TI  - Scintigraphic diagnosis of bile leakage after laparoscopic cholecystectomy. A
      prospective study.
AB  - To assess the role of Tc-99m IDA cholescintigraphy in diagnosing bile leakage and
      bile obstruction after laparoscopic cholecystectomy, 51 studies were performed in
      51 patients on the first postoperative day. Two different radioactive bile acid
      analogs were used, Tc-99m HIDA and Tc-99m trimethylbromo IDA. Scintigraphic
      findings were correlated with the clinical conditions. Results of seven out of 51
      cholescintigrams were abnormal, showing accumulations of activity in the right
      paracolic gutter. Of these seven patients, only three had clinical symptoms
      consisting of more than normal postoperative abdominal pain and peritoneal
      irritation. The other four patients had minimal abnormal accumulation in the
      right paracolic gutter and showed no clinical signs postoperatively. Complete
      common bile duct obstruction or other bile duct-related complications, except for
      bile leakage, were not observed. Cholescintigraphy is feasible for the early
      detection of bile leakage and bile flow obstruction after laparoscopic
      cholecystectomy in patients with increased postoperative abdominal discomfort.

PMID- 1395340
TI  - Transient unilateral reverse ventilation/perfusion mismatch in a patient with
      lung cancer.
AB  - The authors report a transient, unilateral reverse ventilation/perfusion (V/P)
      mismatch in a patient with squamous cell lung cancer. The right lung was well
      perfused but not ventilated (unilateral reverse V/P mismatch). However, lung
      imaging performed 3 days later demonstrated the absence of both perfusion and
      ventilation (V/P match). Reverse V/P mismatch may be a transient process.

PMID- 1395341
TI  - P-32 bremsstrahlung SPECT helps assess intracavitary therapy.
AB  - A patient underwent intracavitary P-32 chromic phosphate therapy for a chest
      tumor. Tc-99m sulfur colloid instilled before the P-32 demonstrated uniform
      distribution of activity throughout the right pleural space, and the P-32 was
      immediately administered. Ten days later, SPECT imaging using bremsstrahlung
      radiation of the P-32 showed an unexpected loculation of the P-32. A subsequent
      chest CT scan demonstrated pleural infolding and fluid localization in the same
      area as the P-32, indicating that the bremsstrahlung SPECT study had, in fact,
      documented the final localization of the P-32, which was unexpected and different
      from the initial localization. The procedure used in this case may be of value in
      documenting the ultimate distribution of intracavitary P-32.

PMID- 1395342
TI  - Wound dressing activity mimicking infection on labeled leukocyte imaging.
AB  - Although labeled leukocyte imaging is an extremely useful technique for the
      localization of infection, false-positive results in inflammatory conditions
      where no infection exists have been described. False-positive results secondary
      to bleeding have also been reported. The authors recently observed intense uptake
      of labeled cells in the wound dressings of two patients undergoing leukocyte
      imaging. Repeat imaging after the removal of these dressings confirmed that the
      activity seen was in the dressings and did not represent focal infection, as
      originally thought. Based on these observations, the authors think it prudent to
      remove such dressings before performing leukocyte imaging.

PMID- 1395343
TI  - Pitfalls of bone mineral density evaluation by dual-photon absorptiometry.
AB  - Material absorbing photons aligned with the lumbar vertebrae can create falsely
      elevated measurements of bone mineral density during dual-photon absorptiometry.
      Three cases illustrating this phenomenon are presented. Although bone mineral
      density was overestimated in each case, calculated fracture risk was normal in
      two cases and greatly increased in the third. Photon-absorbing material can
      create overestimates of bone mineral density during dual-photon absorptiometry,
      even when a greatly increased fracture risk is computed.

PMID- 1395344
TI  - Ice cream scooper's hand. Report of an occupationally related stress fracture of
      the hand.
AB  - Stress fracture of the hand is uncommon but can be a significant source of
      morbidity if not promptly diagnosed. The authors present a case of metacarpal
      stress fracture in which the occupational history was key to the diagnosis and
      management of long-standing hand pain.

PMID- 1395345
TI  - Pott's puffy tumor. Scintigraphic findings.
AB  - The authors describe the scintigraphic findings of bone and Ga-67 imaging
      performed on three patients thought to have Pott's puffy tumor. Two patients did
      indeed have it, but the third patient's "puffy tumor" was a soft tissue abscess.

PMID- 1395346
TI  - Intracerebral platelet accumulation as evidence for embolization of carotid
      origin.
AB  - Arterio-arterial embolism of carotid origin is one major cause of cerebral
      ischemia. To evaluate the role of blood platelets in this process, In-111 labeled
      platelet scintigraphy was performed in a series of 250 patients. Of this number,
      one patient with an 80% carotid stenosis and a normal intracerebral angiogram
      suffered a transient ischemic attack (TIA) several hours after the injection of
      radiolabeled platelets. The scintigram showed a pathologic platelet accumulation
      in the symptomatic carotid area as well as in the ipsilateral brain hemisphere.
      The authors conclude that this scintigraphic finding of hemispheric platelet
      aggregates recorded directly after a clinically observed TIA, together with
      previous observations of retinal emboli after amaurosis fugax attacks, provides
      strong evidence for the arterio-arterial embolic mechanism of TIA.

PMID- 1395347
TI  - Early detection of Rasmussen's syndrome by brain SPECT imaging.
AB  - The authors describe a patient with Rasmussen's syndrome detected by grossly
      abnormal results of Tc-99m HMPAO SPECT brain imaging obtained with a single
      headed camera. Results of magnetic resonance imaging and cerebrospinal fluid
      examinations were normal.

PMID- 1395348
TI  - Reverse crossed cerebellar diaschisis in partial complex seizures related to
      herpes simplex encephalitis.
AB  - Tc-99m HMPAO brain SPECT was performed in a patient who had partial complex
      seizures for 1 year after successful acyclovir treatment of biopsy-proven herpes
      simplex encephalitis 2 years earlier. In spite of antiepileptic medications, her
      seizures were intractable and occurred daily. Tc-99m HMPAO was administered
      intravenously while she was having subclinical seizures, and brain SPECT
      demonstrated an area of hyperperfusion in the right temporal lobe medially and in
      the contralateral cerebellum. This reverse of the crossed cerebellar diaschisis
      phenomenon in epileptic disorders has not previously been documented.

PMID- 1395349
TI  - Normal uptake in a gravid uterus on Tc-99m DTPA imaging.
AB  - A 17-year-old female kidney transplant patient was admitted to the hospital with
      a fever and right lower quadrant pain. Although she was 14 weeks' pregnant, renal
      DTPA imaging was performed because graft rejection was suspected. The study
      revealed fetal uptake of DTPA medial to the transplanted kidney. This has not
      been previously reported. Uptake in a normal uterus has been described using Tc
      99m pertechnetate, Tc-99m glucoheptonate, and Tc-99m MDP. It is essential to
      recognize uptake in the gravid uterus and to differentiate it from uptake
      secondary to a pathologic entity.

PMID- 1395350
TI  - Tc-99m HMDP accumulation in primary peritoneal mesothelioma.

PMID- 1395351
TI  - Portal hypertension evaluated by reprojection images of Tc-99m RBC liver SPECT.

PMID- 1395352
TI  - Reversible septal perfusion abnormality in a patient with left bundle branch
      block on Tl-201 SPECT imaging at rest.

PMID- 1395353
TI  - Bone scintigraphy of a liposarcoma presenting as a muscle hematoma.

PMID- 1395354
TI  - A unique finding on I-123 MIBG imaging: pericardial effusion.

PMID- 1395355
TI  - Multiple extraosseous metastases from osteogenic sarcoma demonstrated on bone
      scintigraphy.

PMID- 1395357
TI  - Tl-201 uptake in recurrent pigmented villonodular synovitis. Correlation with
      three-phase bone imaging.

PMID- 1395356
TI  - Paget's disease presenting as ivory vertebral body with increased uptake on bone
      imaging.

PMID- 1395358
TI  - Demonstration of pleural cerebrospinal fluid leak by In-111 DTPA radionuclide
      myelogram.

PMID- 1395359
TI  - Insulin pens. Is delivery sacrificed to improve patient compliance?

PMID- 1395360
TI  - Vigabatrin. Clinical pharmacokinetics.
AB  - Vigabatrin is a structural analogue of the inhibitory neurotransmitter gamma
      aminobutyric acid (GABA). It is supplied as a racemic mixture, with the S(+)
      enantiomer possessing pharmacological activity. [R,S]-Vigabatrin plasma
      concentrations can be estimated using high-performance liquid chromatographic
      methods. Only gas chromatography-mass spectrometry methods allow quantification
      of the S(+) and R(-) enantiomers. Vigabatrin was rapidly absorbed reaching peak
      concentrations within 1 to 2h. Area under plasma concentration-time curves
      indicated dose-linear pharmacokinetics. There was no effect of food on the
      absorption of vigabatrin. The absorption characteristics of the enantiomers were
      similar to those of the [R,S]-vigabatrin. No chiral inversion was detected after
      administration of the pure S(+) enantiomer. Vigabatrin is not protein bound. The
      apparent volume of distribution of [R,S]-vigabatrin was approximately 0.8 L/kg.
      Despite the lack of protein binding, cerebrospinal concentrations of the [R,S]
      vigabatrin were only 10% of the plasma concentration 6h after a single oral dose.
      The half-life of [R,S]-vigabatrin was between 5.3 and 7.4h, the half-life of the
      enantiomers were 7.5 and 8.1h for the S(+) and the R(-) forms, respectively. The
      major route of elimination was renal excretion; urinary recovery of the [R,S]
      vigabatrin was close to 70%. Pharmacokinetic studies in epileptic children did
      not show any significant effect of maturation on the disposition of the S(+)
      enantiomer: the half-life and the renal clearance were similar to adult values.
      Data suggest a lower bioavailability in children. In adults with epilepsy, the
      half-life of the [R,S]-vigabatrin ranged from 4.2 and 5.6h, similar to that
      measured in healthy adults. In elderly nonepileptic volunteers the
      pharmacokinetics of the enantiomers of vigabatrin showed delayed absorption, a
      major increase in peak concentration and a prolonged half-life. These changes
      were attributed to decreased renal clearance of vigabatrin. A nonlinear
      relationship between renal clearance and creatinine clearance was suggested.
      Vigabatrin caused a 20% fall in plasma phenytoin concentrations, the mechanism of
      which has not been elucidated. There were no other interactions with most
      concurrently administered anticonvulsants. The usual dosage of vigabatrin as add
      on treatment in adults is 2 to 4g daily. Higher dosages up to 80 mg/kg daily were
      required in children. A dosage adjustment was recommended in any patient with
      decreased renal clearance. Although anticonvulsant effects were clearly related
      to dosage, monitoring of plasma concentrations of vigabatrin as a guide to dosage
      is unlikely to be of as much value as with other antiepileptic drugs. The action
      of the drug long outlasts its presence in plasma.

PMID- 1395361
TI  - Liposomal and lipid formulations of amphotericin B. Clinical pharmacokinetics.
AB  - Amphotericin B remains a very important drug for the treatment of fungal
      infections despite its toxicity. Encapsulation of amphotericin B into liposomes
      appears to reduce the toxic effects and to improve the clinical efficacy,
      allowing higher dosages to be given. The exact mechanism behind the reduced
      toxicity is not yet known. Amphotericin B is widely distributed after intravenous
      administration as the deoxycholate solubilisate. The highest concentrations are
      found in the liver, spleen and kidney. Protein binding and binding to the tissues
      is very high. The fate of the drug in the body is not known in detail. Renal and
      biliary excretion are both low and no metabolites have been identified. The drug
      is still detectable in the liver, spleen and kidney for as long as 1 year after
      stopping therapy. The pharmacokinetics of the different liposomal amphotericin B
      or lipid complexes of amphotericin B, which were recently developed, are quite
      diverse. A number of these preparations, such as amphotericin B lipid complex
      (ABLC), 'AmBisome' and amphotericin B colloidal dispersion (ABCD) are in clinical
      development. Their pharmacokinetics depend to a large extent on the composition
      and particle size of the liposomes or lipid complexes. Relatively large
      structures such as ABLC are rapidly taken up by the mononuclear phagocyte system,
      whereas smaller liposomes remain in the circulation for prolonged periods. In all
      studies only the total amphotericin B (both free and liposome- or lipid
      associated) concentrations were determined. There is a need for studies
      correlating clinical efficacy and tolerability of liposomal amphotericin B with
      the pharmacokinetic properties of these formulations.

PMID- 1395363
TI  - Correlating CBC profile and infectious outcome. A study of febrile infants
      evaluated for sepsis.
AB  - The cases of 1,009 febrile infants who were evaluated for sepsis as outpatients
      during a seven-year period were reviewed to correlate their complete blood count
      (CBC) profiles with the infectious outcomes. Eighty-one infants had serious
      bacterial infections (SBIs); the remainder (928) were culture-negative. The
      infants with SBIs had a significantly greater mean total white blood cell (WBC)
      count and absolute band count (ABC) than did those who were culture-negative,
      whereas the difference in mean percent of polymorphonuclear leukocytes was not
      significant. The sensitivity of the ABC was significantly superior to that of
      total WBC count in predicting the outcome of SBI. The diagnostic data provided by
      the ABC can aid physicians in determining the predictive value of CBC profiles
      for infectious outcome in febrile infants receiving outpatient sepsis evaluation.

PMID- 1395365
TI  - Do adolescents understand what physicians say about sexuality and health?
AB  - The high rates of adolescent sexual activity, often with adverse medical and
      social outcomes among minority females, prompted us to survey 160 girls between
      the ages of 13 and 18 concerning their knowledge of reproductive health terms,
      anatomy, and body functions. All were patients in a clinic in an inner-city
      hospital. We hypothesized that adolescents who were older, sexually active,
      and/or had received formal sex education would be better informed. We used a two
      part, self-administered questionnaire. The first part focused on definitions of
      nine common medical and reproductive health terms; the second focused on
      definitions of unlabeled anatomic drawings of male and female genitourinary
      systems. The subjects' responses revealed their lack of information as well as a
      great deal of misinformation. No statistical differences in knowledge were found
      related to age, sexual activity status, or formal sex education. Many patients
      knew only nontechnical and slang terms and did not understand medical terms used
      by physicians in the clinic. Clinicians should not assume similar patients
      (minority and poor) know or understand their terminology and should use simple
      and, if necessary, explicit vocabulary.

PMID- 1395364
TI  - The perioperative management of pheochromocytoma in children.
AB  - The perioperative experiences of 15 children and adolescents who underwent a
      total of 18 surgical procedures for resection of a pheochromocytoma were analyzed
      to determine clinical or hemodynamic events associated with intraoperative or
      postoperative complications. Of the pre- and intraoperative factors assessed,
      only preoperative resolution of symptoms and normalization of blood pressure were
      predictive of uncomplicated outcome. No intraoperative factors were statistically
      associated with outcome, but the four patients with complicated outcomes had had
      aggressively administered intraoperative fluids. Noninvasive measures of cardiac
      function did not help predict outcome; however, echocardiography results were
      available only for six patients. Two of the patients with complicated outcomes
      had cardiac dysfunction, suggesting undiagnosed catecholamine-induced
      cardiomyopathy in the other two with complicated outcomes. Intraoperative fluids
      should be given based on intraoperative blood pressures, the presence or absence
      of prior adrenergic blockade, and assessment of preoperative myocardial function.
      If preoperative myocardial dysfunction is revealed, intraoperative measurement of
      right atrial and pulmonary capillary wedge pressures may be indicated.

PMID- 1395366
TI  - Emergence of invasive group A streptococcal disease among young children.
AB  - Eight cases of invasive group A streptococcal disease in young children were
      reported over a three-month period, February to April 1990. The spectrum of
      clinical disease included: pneumonia with bacteremia (two patients),
      osteomyelitis/septic arthritis (three patients), epiglottitis/supraglottitis (two
      patients), and sepsis without a focus (one patient). Three cases followed chicken
      pox. Three children were in shock at the time of presentation, including one
      child who had a toxic shock-like appearance. Only four children had pharyngitis.
      Bacteremia was confirmed in three children and presumed in another three. All the
      subjects survived. Four isolates of group A streptococci were tested for exotoxin
      A, B, and C (A-0, B-4, C-1) production. These data confirm the reappearance of a
      highly invasive strain of group A streptococci capable of producing a variety of
      clinical diseases, including bacteremia and shock, in a significant proportion of
      victims.

PMID- 1395362
TI  - Glucuronidation of drugs. A re-evaluation of the pharmacological significance of
      the conjugates and modulating factors.
AB  - Glucuronides of drugs are considered to be generally inactive and rapidly
      eliminated. Therefore, these metabolites are often not taken into account in
      evaluating drug effects. The present review describes examples of both direct and
      indirect contributions of glucuronides to net drug effects. Multiple lines of
      evidence indicate that morphine-6-glucuronide has analgesic activity. This
      compound has a high affinity to the mu-receptor, is capable of penetrating the
      blood/brain barrier and is a potent analgesic after administration to patients.
      Indirect activity of glucuronides may consist of a systemic cycle in which an
      active parent compound is derived from the glucuronide by enzymatic action. Such
      systemic cycling has been demonstrated for clofibric acid. In addition, some acyl
      glucuronides are subject to intramolecular rearrangement and the resulting
      metabolites are resistant to beta-glucuronidase. Covalent protein binding of
      glucuronides by different mechanisms may contribute to drug toxicity and immune
      responses. If glucuronides are accepted as potential modifiers of net drug action
      it is important to determine what factors modulate disposition of these
      compounds. Therefore, the later section of this review describes glucuronidation
      under different pathophysiological conditions. Examples for alterations of the
      rate and/or extent of glucuronidation by concurrent diseases processes, age and
      coadministration of other drugs are provided.

PMID- 1395367
TI  - Learning by teaching. A resident-taught oral therapy program for acute diarrhea.
AB  - An educational program on oral rehydration therapy (ORT) for diarrhea was
      instituted in our residents' continuity clinics to evaluate the impact that
      residents teaching parents would have on the knowledge and practices of both
      groups. Sixty-one residents and 287 parents answered the initial written
      questionnaire before the teaching program began, and 48 residents and 147 parents
      completed a second questionnaire at the end of the program. Nineteen residents in
      two clinics were told to participate frequently in teaching the parents, while 29
      residents in three other clinics were given no such instructions. The parents
      were divided into three groups: 58 received teaching and an instructional handout
      on the management of diarrhea; 73 received only the instructional handout; and 16
      received neither intervention. The 19 "teaching" residents had a significantly
      improved overall score compared with the "nonteaching" residents (p < .03). No
      improvement was found in the scores of the 58 parents who received teaching
      compared with those of the 89 parents who received either a handout or no
      educational intervention. We conclude that active teaching of ORT may improve the
      knowledge and practices of residents, but that single teaching encounters,
      whether or not accompanied by written instructions, may have little impact on
      parents.

PMID- 1395368
TI  - The angry patient and family. A clinical approach in the acute medical care
      setting.

PMID- 1395369
TI  - New concepts for steroid use in otitis media with effusion.

PMID- 1395370
TI  - Idiopathic thrombocytopenic purpura in infants under 6 months of age. A
      retrospective study.

PMID- 1395371
TI  - Severe pulmonary hypertension without significant pulmonary parenchymal disease
      in a pediatric patient with acquired immunodeficiency syndrome.

PMID- 1395372
TI  - Chorea following acute glomerulonephritis.

PMID- 1395373
TI  - Hyperpyrexia in an adolescent on desipramine treatment.

PMID- 1395374
TI  - Doppler ultrasound of the hepatic veins: normal appearances.
AB  - Doppler ultrasound of the hepatic veins gives a pulsatile velocity profile which
      mirrors the cardiac cycle. We describe the physiological basis for the complex
      waveform and suggest a venous pulsatility index (VPI) which can be used to
      quantify it. We have studied normal volunteers under differing conditions to
      establish a normal range of VPI. This provides a baseline against which abnormal
      patterns of hepatic vein Doppler can be judged.

PMID- 1395375
TI  - The role of hepatic vein Doppler in diagnosing acute rejection following
      paediatric liver transplantation.
AB  - Serial Doppler ultrasound examinations of the hepatic veins were performed on 50
      consecutive paediatric liver transplants. Damping of the normally pulsatile
      signal was observed in 23 of the 32 biopsy-proven episodes of rejection. In 10
      episodes, the reduction in hepatic vein pulsatility preceded clinical and
      biochemical evidence of rejection by up to 36 h. Seven cases had damped signals
      throughout the post-operative period which precluded assessment by this method.
      In two patients the hepatic vein signals remained pulsatile despite rejection,
      one patient having unsuspected tricuspid regurgitation, and the other a stenotic
      IVC anastomosis. In the 35 liver transplants with normal pulsatility, hepatic
      vein Doppler proved to be a valuable indicator of acute rejection during the
      first 2 weeks following transplantation (sensitivity 92%, specificity 100%,
      positive predictive value 100% and negative predictive value 83%).

PMID- 1395376
TI  - Duplex and colour flow sonography in the diagnosis of post-biopsy arteriovenous
      fistulae in the transplant kidney.
AB  - Arteriovenous fistulae are a common sequel to percutaneous biopsy of the
      transplant kidney. The majority close spontaneously, but a proportion progress
      and may require embolization or surgical closure. They are characterized by a
      very pulsatile (arterialized) venous flow. The arteries sometimes demonstrate a
      low resistive index and/or high velocities, but normal values may be encountered.
      On colour flow Doppler the most characteristic appearance is a mosaic of colour
      due to a combination of tissue vibration and turbulence.

PMID- 1395377
TI  - Transjugular liver biopsy: a review of 200 biopsies.
AB  - Transjugular liver biopsy was performed in 200 patients for whom percutaneous
      biopsy was contraindicated because of coagulation disorders (36%), ascites (32%)
      or for the work-up of portal hypertension (32%). An adequate biopsy allowing a
      histological diagnosis was obtained in 155 patients (77%). The biopsy was
      inadequate in 13 patients (6.5%). In 32 patients (16%) the biopsy failed.
      Complications occurred in 18 patients (9%). Twelve (6%) patients developed liver
      capsule perforations which were immediately embolized without complication.
      Inadvertent carotid artery puncture and supraventricular tachycardias occurred in
      three patients each. Transjugular liver biopsy is a valuable technique which
      provides information which would otherwise be unavailable in those patients for
      whom percutaneous biopsy is considered unsafe.

PMID- 1395378
TI  - Contrast media-induced effects on blood rheology and their importance in
      angiography.
AB  - Factors which alter blood viscosity may have important consequences during
      angiography. The differential effects of various concentrations of five different
      radiocontrast media on the viscosity characteristics of erythrocyte-plasma
      suspensions were made over a range of applied shear rates. The results showed
      that, at both high and low shear rates, the rate of change of viscosity with
      contrast concentration differs markedly between the various types of contrast
      media. The conventional ionic monomers caused most disturbance to blood
      viscosity. The monoionic dimer hexabrix was least disturbing to the viscometric
      characteristics of blood, and the newer non-ionic monomers were intermediate in
      their effects. Significant effects on blood viscosity may be caused by
      radiocontrast agents during a number of in vivo angiographic situations, in
      particular: early after contrast bolus injection into large vessels, in the
      microcirculation after selective injections, and during angioplasty procedures.

PMID- 1395379
TI  - The effect of iodixanol, a new isotonic contrast agent, on femoral blood flow in
      man.
AB  - Both ionic and non-ionic contrast media (CM) injected intra-arterially produce
      peripheral vasodilatation and a sensation of heat or even pain. This effect has
      been considered to be predominantly related to the osmolality of the CM used.
      Iodixanol is a non-ionic dimeric CM which can be made isotonic with blood at
      iodine concentrations up to 400 mg/ml. To assess the degree of peripheral
      vasodilatation following aortic injection of iodixanol, the change in femoral
      artery blood flow has been assessed non-invasively. Dupex ultrasound flow
      velocity records were taken from the contralateral femoral artery in 10 patients
      undergoing transfemoral aortography. Volume flow, mean velocity, pulsatility
      index and peak systolic velocity were continuously recorded before and up to 2
      min after injection of 60 ml of iodixanol at an iodine concentration of 320 mg/ml
      (iodixanol 320). Transient changes consistent with vasodilatation were observed
      in all patients. The greatest changes were observed during the time period 18-24
      s after injection. Volume flow, mean velocity and pulsatility index all changed
      significantly from baseline (mean changes of 80.6%, 73% and -42.7% respectively).
      Peak systolic velocity did not change significantly. Intra-arterial injections of
      isotonic iodixanol 320 produces a significant increase in femoral blood flow in
      man. Factors other than hypertonicity must therefore be implicated in the
      vasodilatory effect of contrast media.

PMID- 1395380
TI  - CT-guided drainage of pelvic abscesses: the peranal transrectal approach.
AB  - Five patients with deep pelvic abscesses underwent computed tomography (CT)
      guided catheter drainage using a transrectal approach. The use of an outer
      removable plastic sheath over the catheter to facilitate positioning and prevent
      inadvertent damage to the mucosal wall is described. This new approach using CT
      guidance is discussed and the alternative routes reviewed.

PMID- 1395381
TI  - Direct puncture venography in subcutaneous cavernous haemangiomas.
AB  - The conventional assessment of subcutaneous cavernous haemangiomas by venography,
      arteriography, ultrasound, computed tomography (CT) or magnetic resonance imaging
      (MRI) is often unsatisfactory and fails to show either the extent of the lesion
      or its feeding and draining vessels. We describe a direct puncture venography
      technique which successfully delineated the lesions in six patients. The
      technique was easy to perform and no complications occurred.

PMID- 1395382
TI  - Can we reduce the number of routine films required for contrast sialography?
AB  - A reduction in the number of radiographs for many investigations has been
      advocated. This study aims to assess the need for control views in sialography
      and whether the post-contrast lateral oblique radiograph would be satisfactory,
      at least initially, as the sole standard post-contrast film.

PMID- 1395383
TI  - Airways obstruction and bronchiectasis: correlation with duration of symptoms and
      extent of bronchiectasis on computed tomography.
AB  - Many patients with bronchiectasis have diffuse airways obstruction and this may
      be the dominant symptom. This study was performed to assess whether the severity
      of airway obstruction in these patients is related to duration of bronchiectatic
      symptoms or to the extent of bronchiectasis demonstrated by computed tomography
      (CT). Twenty-six patients were studied. The severity of airflow obstruction was
      measured by standard physiological testing and the extent of bronchiectasis
      demonstrated by CT was assessed using a scoring system. Correlation was measured
      by Kendall's rank correlation coefficient. A highly significant correlation
      between FEV1 and CT score was demonstrated and a significant correlation was also
      observed between FEV1 and duration of symptoms. A weak correlation was present
      between CT score and symptom duration.

PMID- 1395384
TI  - High resolution computed tomography (HRCT) in emphysema associated with alpha-1
      antitrypsin deficiency.
AB  - Alpha-1-antitrypsin (AAT) deficiency is an inherited disorder associated with an
      increased prevalence of pulmonary emphysema. To date there has been no
      description of the appearances on CT of the emphysema associated with AAT
      deficiency. We have reviewed the CT scans of 17 patients with proven AAT
      deficiency. Eleven out of 17 were examined with HRCT. The CT features were
      correlated with those on chest radiography. Areas of low density corresponding to
      parenchymal destruction and reduced perfusion, and attenuation of the pulmonary
      vasculature were present in all cases. Frank bulla formation occurred in 7/17
      patients and was not a major feature. A striking CT finding was bronchial wall
      thickening and/or dilatation in 7/17 patients with gross cystic bronchiectasis in
      one patient. In contrast to appearances on chest radiography the upper zones were
      affected in all cases (17/17) and fine section scanning was particularly valuable
      in demonstrating changes in these less severely affected regions. Estimation of
      the extent of disease correlated well with abnormal lung function tests.

PMID- 1395385
TI  - Radiological investigation in laparoscopic compared with conventional
      cholecystectomy--an early assessment.
AB  - The implications of laparoscopic cholecystectomy (LC) for radiology were assessed
      by comparing imaging investigations in 48 LC and 48 conventional cholecystectomy
      (CC) patients. In addition, we attempted to identify findings on pre-operative
      ultrasound (US) which predicted operative difficulties at LC. There were no per
      operative or T-tube cholangiograms in the LC patients, but otherwise the pattern
      of investigation was similar in both groups. Forty of the 48 CC patients
      underwent cholangiography (per-operative cholangiography in 36, endoscopic
      retrograde cholangiopancreatography (ERCP) in two, and both in two) demonstrating
      calculi in eight (16.7%) cases. Only four LC patients had cholangiography (ERCP
      in all cases) demonstrating common bile duct (CBD) calculi in one (2.1%) case.
      Ultrasound failed to identify the gall-bladder with certainty in three of the
      five failed LC cases. Neither gall-bladder wall thickness, contraction nor
      calculus size on pre-operative US served as predictors of other per-operative
      difficulties. Our results indicate that there may be some patients with retained
      CBD calculi in the LC group. The role of pre-operative US in predicting operative
      difficulties needs further assessment in a prospective study.

PMID- 1395386
TI  - Ultrasonic and computed tomographic appearances of paraganglioma simulating
      pancreatic mass.
AB  - We report two cases of paraganglioma in which the tumour was situated adjacent to
      the head of the pancreas simulating a pancreatic mass lesion. The absence of
      biliary or pancreatic duct dilatation on ultrasound in the presence of a large
      mass suggested a retroperitoneal tumour rather than a pancreatic adenocarcinoma.
      Functional activity in these tumours is common and should be excluded before
      biopsy.

PMID- 1395387
TI  - Technical report: percutaneous cholecystostomy in acute acalculous cholecystitis.
AB  - Acute acalculous cholecystitis is a significant cause of morbidity and mortality
      in patients with other serious illnesses (Howard, 1981) and the mortality rate
      after surgical cholecystostomy may reach 15% (McGahan and Lindfors, 1989).
      Radiologically controlled percutaneous cholecystostomy is a safe, minimally
      invasive, procedure which may be curative (McGahan and Lindfors, 1989; Berger et
      al., 1989). Both cases described here were successfully treated by percutaneous
      cholecystostomy. A modified Seldinger technique was used in one and a direct
      'trocar' puncture in the other. Percutaneous cholecystostomy, which is
      technically relatively straightforward, is now the treatment of choice for acute
      acalculous cholecystitis.

PMID- 1395388
TI  - Case report: multisystem failure following intravenous iopamidol.
AB  - A case of life-threatening adverse effects following intravenous administration
      of a non-ionic contrast medium is reported. The patient, a 68-year-old diabetic
      hypertensive male with dyspnoea and cough had an abnormal chest radiograph,
      revealing congestive heart failure and an enlarged right hilum. Computed
      tomography (CT) of the chest was performed using 100 cm3 of intravenous
      iopamidol. Within half an hour the patient developed abdominal cramping,
      vomiting, and diarrhoea, followed by hypotension, tachycardia, fever to 40
      degrees C, and delirium. His course was complicated by disseminated intravascular
      coagulation, rhabdomyolysis, renal failure, respiratory arrest, and atrial
      fibrillation. There was no evidence of infection, neoplastic disease, or
      myocardial infarction. Over the next month the patient slowly recovered. One
      other case report implicates a contrast agent with a similar syndrome. The
      features of this case fulfil the criteria for a probable adverse drug reaction of
      a type and severity rarely encountered.

PMID- 1395389
TI  - Case report: superior vena cava obstruction complicated by central venous
      thrombosis--treatment with thrombolysis and Gianturco-Z stents.
AB  - Expandable wire stents can provide effective palliation of superior vena cava
      obstruction (SVCO). We describe a case of SVCO unresponsive to radiotherapy and
      chemotherapy, which was complicated by extensive central venous thrombosis.
      Successful thrombolysis occurred with low-dose streptokinase allowing subsequent
      stent placement.

PMID- 1395390
TI  - Case report: taste of success in thyroglossal fistulography.
AB  - Thyroglossal fistulography is poorly documented in the radiological literature.
      An illustrative case is presented, highlighting the technique employed and the
      significance of its findings. The taste of contrast medium as it spills over the
      tongue is a useful additional sign in the successful demonstration of a fistulous
      communication. The contribution of fistulography to the accurate diagnostic work
      up of patients undergoing the Sistrunk procedure is discussed.

PMID- 1395391
TI  - Case report: granulocytic sarcoma (chloroma) presenting as a cerebellopontine
      angle mass.
AB  - Granulocytic sarcomas (chloromas) are rare, solid extramedullary tumours composed
      of granulocyte precursors occurring in association with granulocytic leukaemia. A
      cerebellopontine angle granulocytic sarcoma in a 4-year-old child presenting with
      unilateral facial palsy is reported. The computed tomographic (CT) findings are
      described, with a review of the literature, and the significance of early
      diagnosis is discussed.

PMID- 1395392
TI  - Case report: solitary haemangioblastoma of the fourth ventricle in an adolescent
      male.
AB  - We report a solitary haemangioblastoma arising from a pedicle in the wall of the
      fourth ventricle of the brain, which we believe to be the first report of
      haemangioblastoma occurring in this location. Computed tomography (CT),
      angiography and magnetic resonance imaging (MRI) made possible accurate pre
      operative tumour identification and localization which facilitated a minimally
      invasive surgical resection.

PMID- 1395393
TI  - Case report: tailgut cyst--assessment with transrectal ultrasound.
AB  - Tailgut cysts are derivatives of the embryonic post-anal gut. Usually
      asymptomatic, they are discovered in adult life as an incidental retrorectal
      mass. Complications include infection, with the formation of retrorectal
      abscesses and occasionally and fistulae, and a long-term risk of malignant
      change, which means that once discovered surgical excision is advised. We present
      a case that was assessed pre-operatively with transrectal ultrasound. The
      findings were of a well defined cystic lesion, with no evidence of invasion. We
      believe that transrectal ultrasound is of value in assessing retrorectal lesions.

PMID- 1395394
TI  - Sodium picosulphate: reaction or drug interaction?

PMID- 1395395
TI  - Splenic-gonadal fusion--the ultrasound appearances.

PMID- 1395396
TI  - Percutaneous transluminal angioplasty of the subclavian and axillary arteries:
      initial results and long term follow-up.
AB  - The early and long term outcomes of 25 subclavian and axillary angioplasties in a
      series of 19 patients treated at one centre over a period of 10 years were
      assessed. The eventual outcome was long lasting improvement in most cases. Two of
      25 PTAs were technical failures as defined as > 30% residual stenosis. Twenty
      three of 25 PTAs were technical successes: 17 of these were first procedures, one
      was a repeat after an initial failure, two were repeats for restenosis and three
      were for separate new lesions. Clinically, 13 of the 19 patients were
      asymptomatic at long term follow-up. Four had only occasional, mild symptoms (in
      one of those they were due to shoulder arthropathy). Two patients had technically
      successful dilatations but developed problems with arterial occlusion distally
      which in one patient required amputation of that limb.

PMID- 1395397
TI  - Thrombin-soaked embolization coils: the effect on whole blood clotting time.
AB  - Embolization coils are well established as embolic agents for the treatment of
      various conditions. Several authors have commented on the increased
      'thrombogenicity' of coils following soaking in thrombin solutions. We have
      carried out an in vitro study, carefully measuring the effect on whole blood
      clotting time (WBCT), of soaking coils in thrombin solutions of different
      concentrations (100, 200, 400, 1000 U/ml). Untreated steel coils are shown to
      have clot promoting activity (CPA) in vitro, reducing WBCT from 14.85 min to 5.53
      min. Passing the coils down a saline-filled catheter slightly reduces their CPA,
      but not significantly (p = 0.21). With thrombin concentrations above 100 U/ml, a
      significant reduction in WBCT is recorded, but although there is a trend of
      increasing CPA with increasing thrombin concentration from 200-1000 U/ml, a
      plateau in WBCT is seen, and the difference is not significant. It therefore
      appears that the clot promoting activity of embolic coils is significantly
      increased by soaking them in a relatively weak thrombin solution. The use of such
      a solution (e.g. 200 U/ml) in vivo would have obvious value in limiting the
      potential systemic effects of thrombin.

PMID- 1395399
TI  - The lateral neck radiograph in suspected impacted fish bones--does it have a
      role?
AB  - A double blind trial, using lateral neck radiographs of 100 patients with proven
      impacted fish bones and 100 normal cases, was conducted to assess the
      sensitivity, specificity and positive predictive value of radiography for
      impacted fish bones. Values of 25.3%, 86.3% and 72.7% respectively were obtained.
      The results are correlated to the clinical findings and reasons for the poor
      performance of radiography are discussed. It is recommended that routine
      radiography for suspected impacted fish bones should be abandoned.

PMID- 1395398
TI  - Renal biopsy in diffuse renal disease--experience with a 14-gauge automated
      biopsy gun.
AB  - The diagnostic and complication rates of 104 percutaneous renal biopsies
      performed for diffuse renal disease in native kidneys were retrospectively
      reviewed. Biopsies were performed by one radiologist using continuous ultrasound
      guidance and a 14-gauge biopsy needle in an automated gun (Biopty TM, Radiplast
      TM, Uppsala). 103 of 104 (99%) biopsies resulted in adequate tissue for a
      definitive histological diagnosis which improves on previously published
      diagnostic rates. Four patients (3.8%) experienced transient macroscopic
      haematuria. There were two symptomatic peri-renal haematomas, both of whom
      required transfusion, and one arteriovenous fistula which was successfully
      embolized (total 2.9% significant complications). Our results compare favourably
      with results using more conventional techniques. We suggest that use of real-time
      ultrasound with the 14-gauge Biopty needle should be the method of choice for
      percutaneous renal biopsy in adults.

PMID- 1395400
TI  - Is radiology a 'nine to five' specialty?
AB  - The role of the radiologist in 'out of hours' radiology was prospectively studied
      in a single Scottish Health Board for a continuous 6 month period. Six hundred
      and sixty seven procedures were performed by radiologists. Computed tomography
      (CT) (274, 41%), ultrasound scans (190, 28.5%) and vascular/interventional
      procedures (60, 9%) were the most frequently performed procedures. Trauma
      accounted for 139 (24%) of all 'out of hours' work and overall 365 (54.7%)
      procedures yielded an abnormality. The workload varied widely between hospitals
      from two procedures per 100 beds to 137 procedures per 100 beds. Similarly the
      input from individual radiologists was very variable. A registrar was present for
      227 (34%) procedures, a senior registrar for 360 (54%) and a consultant for 138
      (20%) (there being two radiologists present for 8.7% of procedures). 'Consultant
      only' radiology departments offering a full radiological service may expect a
      substantial 'out of hours' commitment.

PMID- 1395401
TI  - Case report: ultrasound appearances of a malignant mesothelioma of the tunica
      vaginalis testis.
AB  - A case of a 91-year-old gentleman who developed massive scrotal swelling
      secondary to malignant mesothelioma of the tunica vaginalis testis is presented.
      Preoperative sonography was performed and the findings and difficulty in
      establishing the pathological diagnosis are discussed.

PMID- 1395402
TI  - Case report: tuberculous colitis mimicking Crohn's disease.
AB  - Although intestinal tuberculosis is rare in this country, increasing numbers of
      patients are now being seen, particularly in the immigrant population. We present
      the history of a lady who had acute diarrhoea and in whom the radiological and
      endoscopic findings looked very similar to those seen in Crohn's disease. The
      radiological presentation included widespread aphthous ulceration, a feature that
      has rarely been reported in tuberculous colitis.

PMID- 1395403
TI  - Case report: perforation of angioplasty balloon by Palmaz stent.
AB  - Intravascular stents are recognized to be of value in maintaining patency in
      resistant stenoses, recanalized occlusions, and when intimal dissection has
      occurred during balloon angioplasty [1,2,3]. Apart from early thrombosis,
      complications are relatively infrequent. We report a case of perforation of an
      angioplasty balloon during iliac angioplasty by a Palmaz stent sited in the
      contralateral iliac artery.

PMID- 1395404
TI  - Case report: hepatic ultrasound findings in a case of toxocariasis.
AB  - Multiple hypoechoic areas within the liver may be caused by a large variety of
      disorders. We report a case of Toxocara infestation which produced such an
      appearance within the liver of an 18-month-old child. We believe that this is the
      first report of Toxocara granulomata detected by ultrasound, and suggest that
      ultrasound examination may provide a useful diagnostic clue to this disease.

PMID- 1395405
TI  - Case report: calcification of genioglossus: a painful radiographic finding.
AB  - Resorption of the edentulous mandible can lead to the genial tubercles taking up
      a relatively superficial position. A case is presented where resorption was
      accompanied by calcification of the insertion of genioglossus resulting in the
      development of a painful mass in the floor of the mouth, whose nature could only
      be determined radiographically.

PMID- 1395406
TI  - Case report: paraganglioma of the cauda equina.
AB  - The clinical, radiological and pathological features of a paraganglioma of the
      cauda equina are described, including magnetic resonance imaging features. The
      literature is reviewed and discussed.

PMID- 1395407
TI  - Case report: amoebic liver abscess complicated by a hepatoduodenal fistula.
AB  - Amoebic liver abscess (ALA) is a common extra-intestinal presentation of
      amoebiasis caused by Entamoeba histolytica. The liver abscess may be complicated
      by rupture into adjacent structures. Common organs involved include thorax,
      peritoneum and pericardium. Rupture into the gastrointestinal tract is extremely
      rare. We report a patient who developed a hepatoduodenal fistula complicating an
      amoebic liver abscess. Suspicions were raised on finding air in the liver abscess
      on ultrasound scanning. Diagnosis was confirmed on a water-soluble (Gastrografin)
      swallow (Fig. 1 a,b). Complications of ALA are associated with a high morbidity
      and mortality and early diagnosis is important. To our knowledge only one
      previous case of a hepatoduodenal fistula complicating an ALA with radiological
      confirmation has been reported.

PMID- 1395408
TI  - The radiologist of the future.

PMID- 1395409
TI  - Low osmolar contrast media.

PMID- 1395410
TI  - Inflammatory pseudotumor of orbit.

PMID- 1395412
TI  - Broken choledochal stent.

PMID- 1395411
TI  - Deflating an angioplasty balloon.

PMID- 1395413
TI  - Carcinoma of the larynx--the role of imaging in staging and pre-treatment
      assessments.

PMID- 1395414
TI  - Calf vein anatomy and flow: implications for colour Doppler imaging.
AB  - Early experience has suggested that colour flow Doppler ultrasound may have a
      diagnostic role in calf vein thrombosis. Before its accuracy within the calf can
      be adequately assessed, normal calf vein flow and anatomy needs to be understood.
      We, therefore, studied 40 normal volunteers, age range 24-75 years (mean 45.4),
      M:F 22:18, and assessed both flow and venous diameter in each of the three sets
      of calf veins in the supine and erect positions and once again in both these
      positions following the application of an above knee band. Paired sets of veins
      were present in all posterior tibial and common peroneal sets, but in only 85% of
      the anterior tibial group. Significant flow variations were present between
      different sets of veins, there being relatively less appreciable flow within the
      common peroneal (p < 0.05). Both band application and erect posture produced
      significant increases in venous diameter (p < 0.01, p < 0.001) in the posterior
      tibial and common peroneal veins, aiding visualization but at the cost of
      reducing flow following band application (p < 0.05, p < 0.01). The erect posture
      had no deleterious effect on calf vein flow. We, therefore, recommend that when
      the patency of calf veins is being assessed scanning should be performed in both
      a supine and erect position as this will help vein visualization without a
      reduction in flow, and thus avoid misinterpretation.

PMID- 1395415
TI  - Ultrasound features of low power interstitial laser hyperthermia.
AB  - Low power interstitial laser hyperthermia (ILH) is a reliable means of producing
      in situ thermal necrosis. Ultrasonic studies have been carried out of the changes
      that occur in canine liver during ILH performed at laparotomy. With a single
      fibre delivering Nd-YAG laser at 1-1.5 W for 670 s an hyperechoic region
      developed at the fibre tip measuring 5-6 mm in diameter; around this developed an
      area of hypoechoic change (up to 500s) giving a total area of changed
      echogenicity of 14-16 mm. With a multiple fibre system using 4 laser fibres
      simultaneously the sonographic changes were a summation of the changes seen with
      a single fibre, the hypoechoic areas overlapping. With this four fibre system the
      creation of large (3.5 x 2.8 cm) areas of thermal necrosis was possible. There
      was good correlation between the sonographic and pathological measurements of the
      region of thermal change. The sonographic studies showed the extension and
      overlap of regions of thermal necrosis and allowed visualization and accurate
      measurement of the area undergoing change. The same combined technique has been
      successfully applied in a small number of clinical cases and may be of use in the
      treatment of tumours in solid organs.

PMID- 1395416
TI  - The potential use of diuresis Doppler sonography in PUJ obstruction.
AB  - Three cases of proven PUJ (pelvi-ureteric junction) obstruction in whom duplex
      Doppler sonography was performed are described. In one case, there was a duplex
      transplant kidney with PUJ obstruction of the lower pole moiety. The resistive
      index of an interlobar lower pole artery was markedly elevated compared to that
      of an artery in the upper unobstructed moiety. In the other two cases, the
      resistive index of interlobar arteries of native kidneys increased significantly
      following intravenous frusemide simultaneous with an increase in the degree of
      pelvicalyceal dilatation. It is proposed that diuresis Doppler sonography may
      provide additional diagnostic information in patients with PUJ obstruction, and
      that the method warrants further evaluation.

PMID- 1395417
TI  - Alveolar hydatid disease of the liver: computed tomography and transabdominal
      ultrasound with histopathological correlation.
AB  - The appearances of alveolar hydatid disease of the liver (AHDL) on computed
      tomography (CT) and ultrasound (US) were retrospectively compared with
      histopathological appearances in 67 patients with 100 separate lesions. The
      radiological features were correlated directly with the pathological specimens
      obtained from each patient. We conclude that the CT appearances are more
      specific, but that US has a role to play in mass screening in endemic areas, and
      intraoperatively.

PMID- 1395418
TI  - Staging bladder cancer.

PMID- 1395419
TI  - The Kerley Pergamon Lecture: the role of the radiologist--a chest physician's
      view.

PMID- 1395420
TI  - Transjugular intrahepatic portosystemic stent shunt (TIPSS): early clinical
      experience.
AB  - Transjugular intrahepatic portosystemic stent shunt (TIPSS) is a new percutaneous
      technique for reducing portal venous pressure. We attempted TIPSS in six patients
      with recurrent bleeding for oesophageal or gastric varices between July 1991 and
      January 1992 with success in five. There have been no deaths. One patient re-bled
      after TIPSS. His portal pressure was found to be elevated persistently indicating
      an inadequate shunt. Following further dilatation of the shunt, portal pressure
      fell to a satisfactory level and bleeding has not recurred. No bleeding episodes
      have occurred in the other patients following successful TIPSS. Our series
      contributes to the growing body of experience which suggests that TIPSS is a safe
      and effective treatment for recurrent variceal bleeding.

PMID- 1395421
TI  - Embolization with detachable balloons--applications outside the head.
AB  - Detachable balloons, although widely used as an embolization material in
      neurovascular work, are rarely used outside the head. Yet they offer distinct
      advantages over other methods of embolization in certain situations. They can
      effect an instant and precise occlusion of large arteries and fistulae and unlike
      any other embolization technique the occlusion is reversible until the balloon is
      finally detached. In addition, they can be floated out to distal locations
      inaccessible with more conventional catheter techniques. They are inflated with
      contrast medium or silicone monomers. Large arteries and arteriovenous fistulae
      (AVFs) are best suited to balloon embolization where embolization distal to the
      fistula resulting in parenchymal infarction is not indicated. Thirteen patients
      underwent 14 detachable balloon embolizations. Eleven had large AVFs (4 coronary
      AVFs, 4 Blalock-Taussig shunts, 2 vertebro-vertebral fistulae and 1 renal AVF)
      and three had large arteries (2 aorto-pulmonary collaterals in one patient and 1
      innominate artery pseudo-aneurysm). Twelve of these embolization procedures were
      successful and there were no complications. The two failures were due to
      inability to pass the balloon catheter around an acute angle in the introducer
      catheter and to early deflation. These cases illustrate a wide range of
      situations where balloon embolization may be used successfully. Continued
      refinement and improvement in the technique will allow expansion of the
      indications for non-neurological balloon embolization.

PMID- 1395423
TI  - MRI in diabetes insipidus due to metastatic breast carcinoma.
AB  - Magnetic resonance imaging (MRI) has been established as a valuable imaging
      modality in the evaluation of pituitary disorders. We describe three women with
      known carcinoma of the breast, who presented acutely with biochemically proven
      diabetes insipidus (DI), in whom MRI was used as the primary investigative tool.
      The patients were studied using a 1.5T superconducting system, with gadolinium
      enhancement in two cases. All three had thickened pituitary stalks and two had
      complete loss of the normal high signal from the posterior lobe of the pituitary
      gland. Two also had enlargement of the anterior pituitary gland. One subject was
      also noted to have other metastases to the brain. All three had multiple
      secondary deposits elsewhere in the body and one had metastases to the clivus but
      without evidence of extension to the pituitary fossa. DI is uncommon in systemic
      cancers and anterior pituitary dysfunction much more so, due to the separate
      blood supply of the two lobes. Thickening of the stalk has not been found
      frequently in large autopsy series. In the clinical context of DI in a patient
      with a known primary tumour the loss of high signal from the posterior lobe and
      stalk thickening are indicative of infiltration by metastases. A pituitary mass
      or metastases to adjacent bones are not necessary for diagnosis.

PMID- 1395422
TI  - The current status of embolization in renal cell carcinoma--a survey of local and
      national practice.
AB  - The current role of renal embolization in carcinoma of the kidney is uncertain.
      In order to assess surgeons' opinion of its usefulness a questionnaire was
      circulated to all general urologists practising in Britain and Ireland. Also, a
      series of cases in which the technique was employed (n = 35) was reviewed and
      compared with a similar group who were not embolized (n = 40). There was a 71%
      response to the survey. The principal findings were that all but five urologists
      believe that embolization should not be used routinely in the management of renal
      cell carcinoma. Thirty-five per cent stated that they felt it has a role in
      management of symptoms in metastatic or inoperable tumours. The review of both
      series of patients in our unit shows that embolization (using 95% ethanol infused
      via a balloon occlusion catheter) did not reduce peroperative blood loss and did
      significantly increase hospital stay. There were no deaths in this series, and
      morbidity was confined to 'post-embolization syndrome' in 16 cases. We believe
      that in those cases where embolization is indicated, alcohol infusion via a
      balloon occlusion catheter is a safe and efficient method.

PMID- 1395424
TI  - The imaging characteristics of naso-sinus chondrosarcoma.
AB  - Eighteen patients with histologically-verified naso-sinus chondrosarcomata are
      reviewed, emphasizing their CT and MRI appearances. These tumours present with a
      soft tissue mass expanding and destroying bone and typically (89%) showing areas
      of nodular or plaque-like calcification on CT. The magnetic resonance
      characteristics are more specific and when present with the typical CT features
      are diagnostic of chondrosarcoma. They combine high signal on T2-weighted
      sequences, with differential enhancement on post-Gadolinium T1-weighted scans.
      The contrast enhancement is seen at the periphery of the tumour and the central
      chondromatous core does not enhance. These changes are dependent upon the
      vascularity of the tissues concerned and have been correlated exactly with the
      histopathology of the resected tumour specimens.

PMID- 1395425
TI  - Non-invasive assessment of the Circle of Willis using transcranial pulsed Doppler
      ultrasound with angiographic correlation.
AB  - The ability of transcranial pulsed Doppler ultrasound (TCD) to provide a dynamic
      assessment of the functional capability of the Circle of Willis was assessed
      using conventional cerebral angiography for anatomic correlation. Eleven patients
      had normal four-vessel cerebral angiography prior to being investigated with
      ultrasound. Angiography and ultrasound both demonstrated a functional anterior
      communicating artery in nine of the eleven patients, giving complete agreement
      between the two techniques. Posterior communicating arteries were visualized
      angiographically in all eleven patients. Ultrasound identified bilateral
      functional vessels in nine, the other two patients having non-functional vessels.
      In these latter two patients, angiography demonstrated three of the four
      posterior communicating arteries to be hypoplastic and it was uncertain whether
      these vessels carried significant blood flow. The fourth posterior communicating
      artery was shown to have an absent proximal segment of the ipsilateral posterior
      cerebral artery, with a persistent fetal posterior communicating artery. This
      anatomical variation is a potential limitation of ultrasound for assessing
      functional posterior communicating arteries. These preliminary results indicate
      that a combination of the anatomical (angiographic) and dynamic (ultrasonic) data
      may prove to be complementary for assessing the Circle of Willis.

PMID- 1395426
TI  - Colour flow imaging of calf vein thrombosis.
AB  - Ultrasound and more recently colour Doppler ultrasound has been successfully used
      in the diagnosis of lower limb venous occlusive disease. Colour Doppler
      ultrasound has shown promise in the diagnosis of calf vein thrombosis but to date
      there has been no prospective trial to specifically evaluate its potential. In
      view of this, we carried out a prospective trial of 50 patients comparing the
      accuracy of colour Doppler ultrasound with venography in the diagnosis of deep
      venous thrombosis both above and below knee but in particular with respect to the
      detection of calf vein clot. Of the 50 patients studied, 10 had only one imaging
      modality performed as there were eight venographic failures and two ultrasonic
      failures. Comparison was only thus possible in 40 cases. As in previous studies,
      colour Doppler ultrasound was shown to be accurate in the diagnosis of thrombosis
      within the femoro-popliteal veins and had a sensitivity and specificity of 100%
      respectively. With respect to calf vein lesions, there was one false negative
      scan using the ultrasonic technique giving a sensitivity of 95%, specificity of
      100% and accuracy of 97.5%. We feel colour Doppler ultrasound can and should be
      used as a first line alternative to venography and can be employed for the
      exclusion of both above and below knee deep venous thrombosis. Venography should
      now be reserved for those patients who are unsuitable for ultrasound examination
      or who have an equivocal ultrasound scan.

PMID- 1395427
TI  - Technical report: percutaneous biliary drainage without lateral fluoroscopy.

PMID- 1395428
TI  - Case report: life-threatening hypercalcaemia secondary to pancreatic tumour
      secreting parathyroid hormone-related protein--successful control by hepatic
      arterial embolization.
AB  - Parathyroid hormone-related protein elaborated by pancreatic neuro-endocrine
      tumours can cause life-threatening hypercalcaemia. This is the first reported
      case where hypercalcaemia caused by such a tumour has been successfully
      controlled by hepatic arterial embolization.

PMID- 1395429
TI  - Case report: bronchial artery embolization for life threatening haemoptysis from
      an iatrogenic chronic pulmonary abscess.

PMID- 1395430
TI  - Case report: congenital mediastinal arteriovenous fistula in an adult--diagnosis
      with digital subtraction angiography.
AB  - A case of asymptomatic congenital mediastinal arteriovenous fistula detected in
      an adult patient is presented. The diagnosis was suspected clinically and
      confirmed with intravenous digital subtraction angiography. The clinical and
      radiological features are discussed and the literature reviewed.

PMID- 1395431
TI  - Case report: volvulus of a mesenteric cyst--an unusual complication diagnosed by
      CT.
AB  - A 10-year-old girl presented with colicky abdominal pain and a vague left sided
      mass on physical examination. Plain radiographs of the abdomen were unremarkable
      but ultrasound examination demonstrated a large right sided unilocular cystic
      abdominal mass. Computed tomographic features were diagnostic of volvulus of the
      proximal small bowel with associated mesenteric cyst. Surgery confirmed CT
      findings and no mid gut malrotation was noted at operation.

PMID- 1395432
TI  - Case report: the vanishing ring sign--an unusual CT manifestation of multiple
      sclerosis.
AB  - Ring-like computed tomographic (CT) enhancement of a solitary cerebral mass
      usually indicates neoplasm or abscess. A 64-year-old man with this sign was found
      to have multiple sclerosis (MS), and following oral steroid treatment, it
      disappeared.

PMID- 1395433
TI  - Case report: inverted contrast medium--urine level in the bladder on computed
      tomography.
AB  - Fluid-fluid levels within structures are caused by differences between the
      specific gravity of the fluids. This results in a characteristic appearance on
      computed tomography (CT), with urine which contains contrast medium and has a
      high specific gravity layering posteriorly in the dependent portion of the
      bladder, while lower specific gravity, non-opacified urine is found uppermost. We
      report a patient in whom the contrast medium-urine level was inverted because of
      sediment in the dependent part of the bladder.

PMID- 1395434
TI  - Pre-oxygenation for patients receiving intravenous sedation/analgesia during
      radiologic procedures.

PMID- 1395435
TI  - Retrosternal goitre mobility.

PMID- 1395436
TI  - Pancreatic and renal mobility.

PMID- 1395437
TI  - Duplex Doppler US in medical renal disease.

PMID- 1395438
TI  - Ultrasonic attenuation of fibroadenoma of the breast.

PMID- 1395439
TI  - Randomized controlled trials: lessons from ECMO.

PMID- 1395440
TI  - Endotoxin-induced lung vascular injury: role of platelet activating factor, tumor
      necrosis factor and neutrophils.

PMID- 1395442
TI  - Americans with Disabilities Act update. How to comply.

PMID- 1395441
TI  - September: "Women in Medicine" Month.

PMID- 1395443
TI  - Communicating environmental risk. Patients look to you for information.

PMID- 1395444
TI  - Gravitational stress and volume regulation.
AB  - During the past 3 decades, groundbased experiments have been performed in order
      to investigate the effects of increased and decreased gravitational stress,
      respectively, on the renal response in humans. Experiments that simulate an
      increase in gravitational load (+Gz) to the subjects (centrifugation, passive
      head-up titlt [HUT] or lower body negative pressure [LBNP] have clearly
      demonstrated a decrease in renal sodium and water excretion. Simultaneously,
      increases in plasma levels of arginine vasopressin (AVP), renin activity (PRA),
      aldosterone (PA), norepinephrine (NE) and decreases in ANP have been observed.
      Additionally, experiments that have utilized immersion of seated subjects to
      simulate a decreased gravitational stress (approximately 0 Gz) have demonstrated
      that renal water and sodium excretion increases by 100-400% and that plasma AVP,
      PRA, PA, and NE concentrations are reduced and ANP levels increased. Alternative
      experimental models conducted to simulate the effects of weightlessness in humans
      such as head-down tilt (HDT) and lower body positive pressure (LBPP) have yielded
      less consistent results than those of water immersion (WI) with respect to renal
      function. However, compared to a seated control HDT clearly induces an increased
      rate of renal fluid and sodium excretion. The demonstration that central volume
      expansion during WI is accompanied by an increase in renal fluid and electrolyte
      excretion and that central hypovolaemia during centrifugation, HUT, and LBNP is
      accompanied by the opposite effects indicate that changes in central blood volume
      is an important determinant of the renal functional changes. Results of
      experiments in humans during weightlessness in space are inconsistent and
      difficult to interpret. However, they have indicated that a cephalad
      redistribution of blood and fluid occurs and that this is accompanied by a
      decrease in total body fluid. Experimental models that, respectively, increase
      and decrease the gravitational stress in humans constitute promising tools in the
      investigation of the physiology and pathophysiology of volume regulation.

PMID- 1395445
TI  - Changes in autonomic cardiovascular control in mid-pregnancy.
AB  - Spectral analysis of heart rate variability was used to study autonomic nervous
      control in mid-pregnancy. Fifty women (age 22-36 years) with singleton
      pregnancies (mean duration of gestation 27.7 weeks) and 39 non-pregnant female
      controls (age 21-39 years) were studied using controlled breathing and
      orthostatic tests. During spontaneous breathing the overall heart rate
      variability was lower in pregnant subjects indicating a decreased parasympathetic
      tone at rest. The decreased parasympathetic tone probably counts for the
      increased heart rate in pregnancy. The parasympathetic efferent capacity of
      autonomic cardiac control was found to be similar in pregnant and non-pregnant
      subjects, as no difference was seen during controlled breathing in periodic heart
      rate variability between the groups. Standing up caused a similar change in low
      frequency and mid-frequency bands in both groups, but high frequency heart rate
      variability increased in pregnant subjects and decreased in the controls
      indicating an increased sympathetic tone at rest in mid-pregnancy.

PMID- 1395446
TI  - Critical evaluation of the 'heated-hand-technique' for obtaining 'arterialized'
      venous blood: incomplete arterialization and alterations in glucagon responses.
AB  - In order to test the degree of 'arterialization' and the occurrence of arterio-
      (or capillary-) venous differences in glucose concentrations for commonly used
      blood sampling sites (including the retrogradely cannulated dorsal hand vein with
      application of dry heat to this hand/arm--the 'heated-hand-technique'), oxygen
      partial pressure (oxygen saturation) and plasma glucose was determined in blood
      drawn from different venous sites before and after an oral glucose load (75 g).
      Experiments with and without heating (hot air 68 degrees C) were compared in nine
      healthy volunteers. Basal pO2 (and oxygen saturation) increased in the order
      cubital fossa vein less than superficial forearm vein less than dorsal hand vein.
      Heating raised pO2 by approximately 20 mmHg; P = 0.008) and oxygen saturation (P
      = 0.008-0.02) at all sites, including those on the contralateral arm. Capillary
      venous glucose differences after the glucose challenge were significantly related
      to the sampling site (P less than 0.0001). They were reduced by approximately 50%
      in response to heat exposure (P = 0.008-0.011) and could be correlated to pO2
      values (r = 0.92; P = 0.01). The lowest capillary-venous glucose concentration
      difference was measured with the 'heated-hand-technique' (0.4 +/- 0.1 mmol l-1).
      Heating did not alter integrated incremental glucose (capillary values), insulin,
      and C-peptide-responses and late, counter-regulatory responses (120-240 min after
      glucose) of cortisol, growth hormone, and adrenalin. However, the late glucagon
      response was enhanced (P = 0.011) by heating, concomitant with a significantly
      reduced 'reactive' decrement in glucose concentrations. In conclusion, the
      'heated-hand-technique' provides blood more similar to arterial blood that can be
      obtained from other venous sampling sites. However, significant residual
      differences in pO2 and glucose concentrations remain. In addition, altered
      counter-regulatory hormone responses may occur with heating.

PMID- 1395447
TI  - Exercise echocardiography: a methodological study comparing peak-exercise and
      post-exercise image information.
AB  - It is unclear whether echocardiography at peak bicycle exercise adds information
      to registrations obtained recumbent immediately after the test and what factors
      influence image quality. Therefore, exercise echocardiography was performed
      consecutively and prospectively in 66 men, unselected with regard to
      echocardiography, one month after an episode of unstable coronary artery disease.
      Of 594 segments (9 x 66), 569 (96%) were adequately visualized recumbent at rest.
      The corresponding figures recumbent directly after exercise, seated before
      exercise, and seated at peak exercise were 544 (92%), 474 (80%), and 428 (72%),
      respectively. In the majority of our patients, acceptable images at peak exercise
      were obtained for the septal region, while for the anterior, lateral, and
      inferior segments the success rate varied from 50 to 70%. Recumbent after
      exercise, the success rate was acceptable for most segments, possibly with the
      exception of the apical and lateral segments. Fifty-five patients developed new
      wall motion abnormalities or worsening of wall motion in connection with
      exercise. Echocardiography at peak exercise provided more information than
      afterwards in patients with images of good quality. However, in patients with
      inferior image quality, the registrations obtained recumbent after the test
      revealed wall motion abnormalities which were not obtained seated at peak
      exercise. Patients with worse image quality had significantly higher respiratory
      rate and weight, and rated a higher degree of dyspnoea at peak exercise than
      those with good quality. We conclude that in middle aged men with coronary artery
      disease, image acquisition at peak bicycle exercise and immediately after
      exercise are of complementary value.

PMID- 1395448
TI  - Dependence of maximum performance time on work intensity in patients with a
      hereditary myopathy with succinate dehydrogenase deficiency.
AB  - Patients with a hereditary mitochondrial myopathy with succinate dehydrogenase
      (SDH) deficiency and abnormal lactacidosis during physical exercise have a low
      work capacity when exercising for about 10-15 min. Their maximum voluntary
      muscular strength is fairly normal. The relationship between the time (t) and a
      constant workload (N) that a healthy subject can maximally sustain can be
      expressed as: log t = beta + alpha log N. For normal subjects the constant alpha
      is approximately -5 and the constant beta has a large interindividual variation.
      Of four myopathy patients alpha was determined from two or three maximum bicycle
      exercise tests of different duration (including ramp- and steady-state tests
      using a new application of the method of adding submaximal loads to the final
      maximum workload). The value of alpha varied between -1.0 and -1.81 and beta had
      low values, both significantly different from those of healthy subjects. The
      alpha values explain the divergent results that may be obtained with different
      types of exercise tests in some of these patients, i.e. a normal or moderately
      reduced capacity in exercise tests of short duration (for example a short
      Tornvall or a ramp type of test) and a very low exercise capacity in tests of
      longer duration (for example a steady state type of test with workloads chosen to
      allow at least two loads). The low absolute value of alpha may be related to the
      abnormally increased anaerobic metabolism of these patients during exercise,
      caused by the SDH deficiency.

PMID- 1395449
TI  - Distribution of radioactive aerosol in the airways of children and adolescents
      with bronchial hyper-responsiveness.
AB  - The purpose of this study was to examine the relationship between the pulmonary
      distribution of inhaled radioaerosol, bronchial responsiveness, and lung function
      in children and adolescents. The participating subjects (n = 39) were divided
      into three groups: (1) 14 asthmatics with bronchial hyper-responsiveness (BHR),
      (2) five non-asthmatic subjects with BHR, and (3) 20 controls without BHR.
      Pulmonary distribution of [99Tcm) albumin radioaerosol, maximal expiratory flow
      when 25% of forced vital capacity remain to be exhaled (MEF25), and bronchial
      responsiveness to inhaled histamine were measured. Twenty subjects (52%) had
      irregular central distribution and 19 subjects (48%) had regular distribution of
      radioaerosol in their lungs. No difference in distribution of radioaerosol was
      found between the three groups of children. The median MEF25 among non-asthmatic
      subjects (80% predicted) was lower than that found in controls (92% predicted)
      but higher than that found in asthmatic subjects (55% predicted). A relationship
      was found between reduced flow at the peripheral airways, as indicated by MEF25
      and the degree of central distribution of radioaerosol. Furthermore, subjects
      with irregular central distribution of radioaerosol had an increased degree of
      bronchial responsiveness. In conclusion, children and adolescents who have flow
      rates in the peripheral airways or increased degree of bronchial responsiveness
      tend to have abnormal distribution of radioaerosols.

PMID- 1395450
TI  - Pulmonary clearance of 99mTc--DTPA and 99mTc-albumin in rabbits with surfactant
      dysfunction and lung injury.
AB  - We measured the pulmonary clearance of inhaled 99mTc-DTPA and 99mTc-albumin in
      rabbits with surfactant dysfunction induced by dioctyl sodium sulphosuccinate and
      in rabbits with lung injury induced by oleic acid. The animals were
      tracheotomized and mechanically ventilated. After inhalation of 99mTc-albumin in
      ten animals, clearance of the tracer from the lungs was monitored for 90 min. The
      first 30 min was a control period. Dioctyl sodium sulphosuccinate was then
      administered in aerosol and after another 30 min oleic acid was injected
      intravenously. Ten other rabbits were given 99mTc-DTPA, and clearance was
      externally recorded for 60 min. Five animals inhaled detergent aerosol and five
      animals were given oleic acid intravenously after 30 min. Airway pressures, tidal
      volume, and arterial blood gases were measured before and after each
      intervention. The half-life of 99mTc-albumin in the lung was 442 +/- 123 min
      during the control period, 363 +/- 52 min after detergent administration, and 134
      +/- 18 min after oleic acid administration (P less than 0.05 compared to control
      and P less than 0.01 compared to the period after detergent). The half-life of
      99mTc-DTPA was 94 +/- 16 min before and 10 +/- 0.6 min (P less than 0.01) after
      detergent administration and 75 +/- 12 min before and 18 +/- 1.8 min (P less than
      0.01) after oleic acid administration. Gas exchange was not affected by
      administration of dioctyl sodium sulphosuccinate but markedly impaired after
      injection of oleic acid. Compliance of the respiratory system remained unaffected
      by detergent but decreased after injection of oleic acid.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1395451
TI  - Miniature silicon diode matrix-detector for in vivo measurement of 133xenon
      disappearance in the canine myocardium following local tissue injection.
AB  - After local tissue depositioning of 133Xenon (133Xe) the regional washout is
      usually registered by a NaI(Tl) detector. The residual radioactivity of 133Xe is
      usually measured at its 81 keV photopeak. However, using small Silicon (Si)
      photodiodes it is feasible to measure only the low-energy activity in the X-ray
      energy range. In the myocardium of open chest dogs 133Xe washout measurements by
      a matrix of Si diodes composed in a 4 x 4 array and a conventional NaI(Tl)
      detector were carried out simultaneously. Fourteen separate pairs of measurements
      were performed in 3 dogs. When the Si-diodes in the matrix were selected
      individually in accordance to the position with reference to the diode with
      maximum count rate or pooled, comparisons could be made between the corresponding
      washout rate constants measured by the reference detector. In the correlation
      between the rate constants the intercepts with the y axis were not significantly
      different from zero allowing the correlation lines to be fitted through (0.0).
      The slope of the correlation line was close to unity. The registration of the low
      X-ray energy of 133Xe by the Si-detectors is an alternative to the conventional
      high energy activity recording appearing from the gamma-energy of the photopeak.
      The detector matrix concept allows elimination of motion artefacts and indicator
      distribution in the myocardial tissue. Due to the uniformity and low cost of Si
      diodes the perspective may be the introduction as a disposable transducer useful
      during cardiac surgery for example.

PMID- 1395452
TI  - [The effect of the use of sinusoidal modulated currents on the recovery of
      athletes].
AB  - Modular sinusoidal currents were used to optimize the recovery process of the
      force of athletes' muscles. 113 elite athletes were analyzed. They were
      participants in rowing, cycling, tennis and Greco-Roman wrestling. In all cases
      the modular sinusoidal currents were applied to the dorso-cervical and lumbar
      regions. It was found that applications to the dorso-cervical regions normalize
      the altered parameters of the cardiovascular system and increase the capacity of
      the humeral muscles to contract. Furthermore they stabilize the adrenergic
      sympathetic zone and stimulate the immune system.

PMID- 1395453
TI  - High density lipoprotein cholesterol low serum level as the only risk factor in
      male patients with coronary heart disease.
AB  - Forty-three male patients with myocardial infarction, severe angiographic
      coronary lesions, high or normal low density lipoprotein (LDL) cholesterol serum
      levels, and without other risk factors for coronary heart disease were selected.
      In all patients high density lipoprotein (HDL) cholesterol and HDL
      cholesterol/total cholesterol ratio were significantly lower than in the control
      group; in particular, the ratio was below 0.240 which was the median value of
      normal subjects. Six patients with total cholesterol and LDL-cholesterol below
      5.16 and 3.35 mmol/l respectively, had low serum levels of HDL-cholesterol; in 4
      of them the value of this risk factor was below 0.9 mmol/l; 2 of 6 patients had a
      lipoprotein (a) serum concentration above 0.3 g/l but not a premature myocardial
      infarction or a clinical history of coronary heart disease. Our data confirm that
      HDL-cholesterol/total cholesterol ratio could be a better marker of coronary
      heart disease than HDL-cholesterol, total cholesterol or LDL-cholesterol and
      suggest the importance to check HDL-cholesterol serum levels also in subjects
      without risk factors for atherosclerotic disease.

PMID- 1395454
TI  - [The otilonium bromide-benzodiazepine combination in the therapy of the irritable
      colon syndrome].
AB  - The irritable bowel syndrome is classified ad "disturbance of intestinal motility
      without an identifiable anatomic substrate". However, the clear etiopathogenetic
      implications of a psychosomatic nature complicate the search for an adequate
      therapeutic strategy. Based on this clinical experience, we set out to check the
      importance of a spasmolytic with a benzodiazepine and the tolerability of this
      type of combination. We therefore compared the results in 60 patients with
      irritable bowel syndrome of 8 weeks' treatment with tablets containing octylonium
      bromide (OB) 20 mg plus diazepam (DZ) 2 mg or OB 40 mg + 2 mg DZ. The doubling of
      the spasmolytic without increasing the daily dose of anxiolytic appeared to be
      useful for reducing the symptoms typical for the irritable bowel syndrome. In
      addition, the combination was found to be perfectly tolerated.

PMID- 1395455
TI  - [Otilonium bromide-diazepam in the treatment of the irritable colon. A controlled
      study versus otilonium bromide].
AB  - Octylonium bromide (OB) is a drug with spasmolytic properties acting selectively
      on the smooth muscle of the gastrointestinal tract by interfering with calcium
      mobilization from extra- and intra-cellular deposits. The etiopathogenetic
      implications of a psychosomatic nature of the irritable bowel syndrome amply
      justify the use of a spasmolytic (OB) with a benzodiazepine. In our study, we
      compared the combination OB + DZ (20 mg + 2 mg) T.I.D. versus OB alone (20 mg) in
      30 patients suffering from irritable bowel syndrome. The double-blind study
      lasting 3 weeks was aimed at evaluating gastrointestinal symptoms (bowel motions,
      aspect of faeces, abdominal pain, pre-evacuation pain, bloating) during the three
      days preceding the study and during the last five days of treatment, as well as
      the anxiogenic situation as assessed by the STAI scale (State Tract Anxiety
      Inventory) before and at the end of the treatment period. The results obtained
      showed that both treatments considerably reduced gastrointestinal symptoms even
      though OB alone did not appear to be equally effective and the anxiety component
      was significantly reduced only by treatment with the combination. The absence of
      side effects and the perfect tolerability of both treatments showed the OB + D
      combination T.I.D. to be the treatment of choice for patients suffering from
      irritable bowel syndrome.

PMID- 1395456
TI  - [The prevalence of rhinopharyngeal staphylococcal carriers among those employed
      in the communal food services of the province of Rome].
AB  - Microbial food contamination is at present less frequent than in the past.
      Nevertheless, Staphylococcus aureus food poisoning is still among the most
      frequent ones in Italy. The authors screened nasal swabs of 112 person working in
      five communal feeding services in Rome province; of these, 53 were found to be
      positive. This percentage (48.3%) does not differ substantially from those found
      by other researchers in various Italian cites.

PMID- 1395458
TI  - [Consumer behaviors in obesity due to overeating. The usefulness and limits of
      diet therapy].
AB  - Appropriate dietary prescription has still a useful place in a weight reducing
      program, but no such program must be prescribed before careful evaluation of the
      risk for psychological derangement that may be the consequence. A rational
      interdisciplinary approach is essential. The importance of correcting a sedentary
      life style must not be overlooked.

PMID- 1395457
TI  - [A comparison between computed tomography and magnetic resonance in the
      verification of prolactinomas].
AB  - First, computer tomography and subsequently magnetic resonance have profoundly
      changed the diagnostic protocol for the study pituitary pathology. Conventional X
      ray and examination with the use of contrast media are being employed less and
      less. Tomographic techniques (CT and RM) permit direct identification of
      anomalies as well as precise evaluation of their relationship with surrounding
      structures.

PMID- 1395459
TI  - Diabetes and the Clinical Standards Advisory Group.

PMID- 1395460
TI  - Blood glucose control and diabetic microvascular complications: long-term effects
      of near-normoglycaemia.

PMID- 1395461
TI  - Parity, ethnic group and the prevalence of type 2 diabetes: the Coventry Diabetes
      Study.
AB  - The prevalence of Type 2 (non-insulin-dependent diabetes) in relation to parity
      was compared among South Asian (Asian) and European women during a cross
      sectional house-to-house screening programme for diabetes in Foleshill, Coventry,
      UK. The parity of female residents was ascertained in 8 of the 12 areas visited.
      These areas contained 2096 European (68 with diabetes diagnosed) and 1148 Asian
      women (95 with diabetes diagnosed). Crude prevalence of Type 2 diabetes was 3.2%
      and 14.7% in Europeans aged 30-64 years and > or = 65 years, respectively, and
      10.9% and 36.5% in similarly aged Asians, respectively. In those aged 30-64
      years, the age and body mass index adjusted prevalence of Type 2 diabetes was
      highest among nulliparous (Europeans 4.4%, Asians 16.3%) and grand multiparous
      (parity > or = 5: Europeans 6.3%, Asians 16.5%) women when compared with women
      who had had 1 or 2 deliveries (Europeans 0.9%, Asians 3.3%, p < 0.001, both
      ethnic groups). However, parity had no effect among women aged > or = 65 years.

PMID- 1395462
TI  - The prevalence, detection, and epidemiological correlates of peripheral vascular
      disease: a comparison of diabetic and non-diabetic subjects in an English
      community.
AB  - A cross-sectional study was performed to investigate the distribution, methods of
      detection, and potential risk factors for peripheral vascular disease in a
      diabetic population with comparison to an age and sex matched non-diabetic group.
      The population came from a geographically defined area consisting of 10 general
      practices (total list size 97,034) and covered rural and urban districts of East
      Dorset. Peripheral vascular disease was defined as an ankle/brachial Doppler
      pressure ratio of 0.9 or less. Of the diabetic subjects reviewed, 864 were
      classified as having Type 2 diabetes and 213 Type 1 diabetes. The prevalence of
      peripheral vascular disease in Type 1 diabetes was 8.7% (95% CI 4.9-12.5) and in
      Type 2 diabetes 23.5% (95% CI 20.5-26.5), which after adjusting for age was not
      significantly different (odds ratio 1.5, 95% CI 0.8-2.7, p = 0.18). There was no
      difference in the frequency of symptomatic peripheral vascular disease or the
      site of occlusion between diabetic and non-diabetic subjects with peripheral
      vascular disease. Age, cerebrovascular disease, coronary artery disease, glucose,
      body mass index, and cholesterol in Type 2 diabetes and age and proteinuria in
      Type 1 diabetes were significant predictors of peripheral vascular disease. In
      the non-diabetic group, age and cigarettes smoked were significant variables.
      These findings suggest that clinical features of peripheral vascular disease in
      diabetic and non-diabetic subjects are similar but risk determinants may be
      different.

PMID- 1395463
TI  - Clinical examination versus neurophysiological examination in the diagnosis of
      diabetic polyneuropathy.
AB  - Several methods have been used to diagnose diabetic polyneuropathy and to
      quantitate the degree of affection of peripheral nerves. Using a newly developed
      scoring system we compared bedside clinical examination with neurophysiological
      examination in a group of 78 diabetic patients. Individual scores for clinical
      examination were significantly correlated with scores for neurophysiological
      examination (r = 0.7, p < 0.0005). All 78 patients had at least one clinical
      symptom or sign of polyneuropathy. Clinical examination indicated polyneuropathy
      in three patients with neuropathic complaints, while neurophysiological
      examination in these patients showed no abnormalities. In 12 out of 14 patients
      with normal neurophysiological sensory nerve function, clinical examination
      showed at least one abnormal sensory modality. Comparing the four different
      sensory modalities, light touch sense and pinprick sense indicated polyneuropathy
      better than vibration or position senses. An abnormal Hoffmann reflex of the
      soleus muscle was always associated with a decreased or absent ankle jerk. The
      scoring system for the clinical examination proved useful for diagnosing and
      quantitating the severity of diabetic polyneuropathy. Clinical sensory deficits
      could not be inferred from the results of neurophysiological testing of sensory
      nerve function. Pinprick sense, light touch sense, and ankle jerks were the most
      important parameters in the clinical diagnosis of diabetic polyneuropathy.

PMID- 1395464
TI  - The effect of weight-bearing pressure on the plantar circulation in diabetes
      mellitus.
AB  - Patients with diabetic neuropathy are prone to ulceration on the sole of the
      foot, especially in areas with high weight-bearing pressure. The relationship
      between weight-bearing pressure and nutritive skin circulation in the plantar
      region was studied. Gait analysis was performed with the EMED Gait Analysis
      System and the skin circulation was measured by fluorescein flowmetry in ten
      neuropathic diabetic patients and in eight healthy controls. The critical plantar
      foot pressure above which nutritional blood flow in the skin was arrested was 3 N
      cm-2 or more in both diabetic and control subjects. Below 3 N cm-2 the blood flow
      was independent of weight-bearing pressure both in diabetic and control subjects
      (correlation coefficient r = -0.01 and -0.19, respectively). Thus, our results
      indicate that the nutritional blood flow in the plantar region is not decreased
      in patients with diabetic neuropathy.

PMID- 1395465
TI  - Prevalence of haemochromatosis amongst patients with diabetes mellitus.
AB  - Four hundred and six white caucasian patients with diabetes mellitus (243 male,
      mean age 54 +/- 16 (SD) years) were screened for haemochromatosis. Four patients
      had a fasting transferrin saturation > 62% and all were HLA A3 positive. Two were
      probable homozygotes for haemochromatosis and two heterozygotes. Homozygote
      haemochromatosis prevalence in this diabetic population was therefore 2/406
      (0.0049) which is identical to that reported in the general population. These
      findings do not support a genetic relationship between the two conditions.

PMID- 1395466
TI  - Effect of chronic ACE inhibition on glucose tolerance and insulin sensitivity in
      hypertensive type 2 diabetic patients.
AB  - The question, of whether long-term treatment of essential hypertension with
      angiotensin-converting enzyme (ACE) inhibitors is capable of modifying glucose
      tolerance or insulin sensitivity in Type 2 (non-insulin dependent) diabetes, is
      still unsolved. We studied 14 moderately overweight Type 2 diabetic patients with
      essential hypertension in stable metabolic control after a run-in period and
      again after 3 months of antihypertensive treatment with the ACE inhibitor,
      captopril. Glucose tolerance was tested with a 75-g oral glucose load and insulin
      sensitivity was measured by the insulin suppression test, while dietary and drug
      treatment of the diabetes remained constant. In the whole group, mean blood
      pressure (MBP) fell progressively over 3 months from a baseline value of 123 +/-
      3 mmHg to a final value of 115 +/- 2 mmHg (p < 0.005); in six patients, the
      change in MBP was < 5 mmHg (non-responders), thus giving a clinical response rate
      of approximately 60%. After treatment, fasting plasma glucose, insulin, free
      fatty acid (FFA), potassium, and glycated haemoglobin concentrations were
      unchanged from baseline. During the oral glucose tolerance test, the incremental
      glucose area-under-curve was 0.75 +/- 0.05 mol 120 min l-1 before and 0.76 +/-
      0.06 mol 120 min l-1 after treatment (p = ns). Endogenous insulin response and
      suppression of plasma FFA levels were superimposable on the two occasions. During
      the insulin suppression test, steady-state plasma glucose levels were 14.4 +/-
      1.3 vs 14.2 +/- 1.1 mmol l-1 before and after chronic ACE inhibition,
      respectively, at comparable hyperinsulinaemic plateaux (291 +/- 21 vs 287 +/- 14
      pmol l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395468
TI  - Distinguishing between persistent and transient impaired glucose tolerance using
      a prediction model.
AB  - Screening for impaired glucose tolerance (IGT) and Type 2 (non-insulin dependent)
      diabetes was carried out in 777 people and those with high blood glucose levels
      completed three 2-h oral glucose tolerance tests (OGTT). Blood lipid levels,
      fasting and 2-h insulin levels, body mass index, and blood pressure were also
      measured and family history of Type 2 diabetes recorded. Fifty people were
      identified with IGT and of these 21 were found to have persistent IGT and 29
      transient IGT. A model including the variables body mass index, fasting and 2-h
      insulin levels, fasting triglycerides and family history of Type 2 diabetes was
      developed using the Speigelhalter-Knill-Jones weighting method to predict
      subjects with persistent IGT. This model could be useful in identifying people
      with persistent IGT and therefore eliminate the need for repeat OGTTs which are
      time consuming and expensive.

PMID- 1395467
TI  - Influence of ripeness of banana on the blood glucose and insulin response in type
      2 diabetic subjects.
AB  - Banana is a popular and tasty fruit which often is restricted in the diet
      prescribed for diabetic patients owing to the high content of free sugars.
      However, in under-ripe bananas starch constitutes 80-90% of the carbohydrate
      content, which as the banana ripens changes into free sugars. To study the effect
      of ripening on the postprandial blood glucose and insulin responses to banana, 10
      type 2 (non-insulin-dependent) diabetic subjects consumed three meals, consisting
      of 120 g under-ripe banana, 120 g over-ripe banana or 40 g white bread on
      separate days. The mean postprandial blood glucose response area to white bread
      (181 +/- 45 mmol l-1 x 240 min) was significantly higher compared with under-ripe
      banana (62 +/- 17 mmol l-1 x 240 min: p < 0.01) and over-ripe banana (106 +/- 17
      mmol l-1 x 240 min: p < 0.01). Glycaemic indices of the under-ripe and over-ripe
      bananas differed (43 +/- 10 and 74 +/- 9: p < 0.01). The mean insulin response
      areas to the three meals were similar: 6618 +/- 1398 pmol l-1 x 240 min (white
      bread), 7464 +/- 1800 pmol l-1 x 240 min (under-ripe banana) and 8292 +/- 2406
      pmol l-1 x 240 min (over-ripe banana). The low glycaemic response of under-ripe
      compared with over-ripe bananas may be ascribed to the high starch content, which
      has previously been found to be only hydrolysed slowly by alfa-amylase in
      humans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395469
TI  - Foot infections in diabetes are rarely due to a single microorganism.
AB  - The purpose of this study was to investigate the frequency with which multiple
      organisms can be isolated from severe foot infections in diabetic patients with
      carefully planned techniques of collection and processing of specimens. One
      hundred and seventy-seven organisms were isolated from 52 patient admissions
      (mean 3.4 per infection) at a district hospital. This was compared to a mean of
      2.1 organisms per lesion at a local university hospital and 2.3 at a smaller
      community hospital. Staphylococcus aureus was isolated in about half of all
      lesions at the three hospitals, while anaerobic organisms were isolated from 30
      at the district hospital, 10 at the university hospital, and 4 at the community
      hospital. This study concludes that, firstly, proper techniques for collection,
      transportation and examination of culture specimens are important in the
      isolation of multiple organisms from foot infections in diabetes, and secondly,
      Staphylococcus aureus is often absent while anaerobic organisms are common.

PMID- 1395470
TI  - An audit of the management and outcome of hospital inpatients with diabetes:
      resource planning implications for the diabetes care team.
AB  - In order to assess the outcome of hospitalized diabetic patients in an urban
      health district the notes of a cohort identified from a survey of all inpatients
      on a single day in spring 1990 were reviewed. One hundred and ten cases were
      reviewed (8.4% of all inpatients); median age 73 years (range 26-99), 59 female.
      Fifty-five percent were medical patients (general or geriatric) and 16% were
      general surgical. Six remained inpatients after 6 months. Sixteen died, of whom
      10 had macrovascular disease. Median length of stay was 22 days (2-300),
      significantly above the district average in all specialties (< 10 days). Of 15
      patients with foot problems, 5 died and 3 had major amputations. Only 23% of all
      patients had documented evidence of screening for diabetic complications. The
      discharge diagnoses failed to acknowledge diabetes in 54 cases (including 10
      deaths). Only 10% had formal advice from the diabetes team and subsequent audit
      revealed that metabolic management was commonly suboptimal in non-physician
      units. These data suggest that inpatient diabetes is costly and carries a high
      mortality. The incidence is substantially underestimated by conventional episode
      statistics. The evidence from this cohort of diabetic inpatients suggests that
      improved communication and recognition of the importance of diabetes could
      usefully contribute to the quality of care achieved.

PMID- 1395471
TI  - The effect of a city-wide mass media campaign on the public awareness of
      diabetes.
AB  - The aim of this study was to determine whether a mass media campaign about
      diabetes would increase public awareness and knowledge of diabetes, leading to an
      increased rate of detection of previously undiagnosed cases. A telephone
      questionnaire was administered to two groups of randomly selected members of the
      public before and after a 1-week mass media campaign. Cases of newly diagnosed
      diabetes were monitored by general practitioners. The median knowledge score rose
      from 5 (range 0-10) before the campaign to 6 (0-10) afterwards, p < 0.001. The
      knowledge score for a control group, questioned post-campaign only, was also 6 (1
      10). The increase in the median knowledge score was mainly as a result of more
      people being able to define diabetes and give two presenting symptoms. This
      increased awareness did not however result in an increase in detection of new
      cases.

PMID- 1395472
TI  - A proposal for continuing audit of diabetes services. Home and Members of a
      Working Group of the Research Unit of the Royal College of Physicians and British
      Diabetic Association.
AB  - A working group was established in order to suggest the process and outcome
      variables most appropriate for the continuing audit of diabetes services. The
      proposed audit is being piloted in hospitals in selected United Kingdom Health
      Districts. The main process and outcome measures suggested are: waiting and
      consultation times; missed or cancelled appointments; information given to
      patients and the primary care team; knowledge of diabetes and risks of smoking;
      recording of key examinations and investigations, i.e. levels of glycosylated
      haemoglobin (or equivalent), serum cholesterol, body mass index, blood pressure,
      albumin excretion rate, presence and extent of retinopathy, history of coronary
      artery, cerebrovascular or peripheral vascular disease; history of severe
      hypoglycaemia; presence of foot problems; psychological well-being; patient
      satisfaction; admission rates and hospital bed days for hyperglycaemic and other
      diabetes related emergencies.

PMID- 1395473
TI  - Evidence for reversibility of defective counterregulation in a patient with
      insulinoma.
AB  - To investigate her unheralded neuroglycopenia, a 45-year-old woman was studied
      before and 3 months after removal of her insulinoma. Hypoglycaemia was induced
      and reversed by glucose infusion during 4-h insulin infusions (1.5 mU kg-1 min
      1). Postoperatively, the low preoperative adrenaline, noradrenaline, growth
      hormone, and cortisol responses increased by 490, 152, 64, and 178%,
      respectively, and started at higher glucose levels (2.7 vs 1.9 mmol l-1 for
      adrenaline), with a four-fold increase in autonomic symptoms and more profound
      psychomotor dysfunction. We conclude that the syndrome of recurrent severe
      hypoglycaemia with defective warning symptoms and hormonal responses, in this
      case induced by an insulin-secreting tumour, is reversible, perhaps by the
      removal of the hypoglycaemia, a finding which may be relevant to other patients
      with recurrent severe hypoglycaemia.

PMID- 1395474
TI  - The role of the general practitioner in diabetes care.

PMID- 1395475
TI  - Description of a diabetes support group: lessons for diabetes caregivers.
AB  - A weekly psychotherapy group has been established with 21 diabetic patients (mean
      sessions attended per patient 12.0 +/- 8.9). In this non-structured group, the
      topics spontaneously chosen most often for discussion included complications and
      fears regarding complications, diet, and relationships with physicians. Other
      topics included difficulties achieving diabetes control, relationships with
      families, devices for day to day management, pregnancy and parenting, depression
      and eating disorders, and occupational concerns including driving and diabetes.
      The presence of a physician co-therapist was found to be valuable. Examples are
      provided of the patients' concerns. It is felt that understanding patients' needs
      for information and communication with physicians and allied health professionals
      will enrich the caregiver-patient relationship.

PMID- 1395476
TI  - Human insulin and lipoatrophy.

PMID- 1395478
TI  - Disposal of needles and plastic syringes.

PMID- 1395477
TI  - Resistance to injection: the 1991 RD Lawrence Lecture.

PMID- 1395479
TI  - Type I diabetes in children in Riyadh: seasonal variation.

PMID- 1395480
TI  - Failure to detect autoantibodies to islet amyloid polypeptide in sera from type 1
      diabetic patients.

PMID- 1395481
TI  - British Diabetic Association's Education Section Annual Conference and Medical
      and Scientific Section Autumn Meeting. September 1-4, 1992. Abstracts.

PMID- 1395482
TI  - Super-elasticity and thermal behavior of Ni-Ti alloy orthodontic arch wires.
AB  - Bending properties and thermal behavior of twenty commercial Ni-Ti alloy
      orthodontic arch wires were investigated quantitatively to characterize their
      suitability for clinical use. There was substantial difference among the load
      deflection curves obtained by a three-point bending test. Some wires exhibited
      super-elasticity; load decreased little with decreasing deflection. Others showed
      good spring-back properties only; load was nearly proportional to deflection.
      Thermal behavior due to phase transformation of the alloy was examined by
      differential scanning calorimetry (DSC). Some of the wires did not have the
      correct transformation temperatures to exhibit super-elasticity at body
      temperature. Moreover, thermal behavior was closely related to super-elasticity.
      There were clear thermal peaks in the DSC curves of the super-elastic wires.
      However, wires without super-elasticity had no peak in the DSC curves.

PMID- 1395483
TI  - Hemolytic activity of a dental adhesive monomer (N-methacryloyloxy-5
      aminosalicylic acid, MASA) and its interaction with phospholipid liposomes as
      studied by NMR and DSC.
AB  - N-methacryloyloxy-5-aminosalicylic acid (MASA) has recently been used as an
      adhesive primer in restorative resin systems. To monitor the biological activity
      of MASA, we studied changes in NMR-chemical shifts (delta H) and the differential
      scanning calorimetry (DSC) phase transition temperature (Tm) of
      dipalmitoylphosphatidylcholine (DPPC)/MASA liposomes with or without the presence
      of albumin and collagen. The delta H and the Tm did not alter significantly and
      the interaction of MASA with DPPC was found to be small. Hemolytic activity of
      MASA was markedly smaller than that of the phosphate monomer (MDP) in bonding
      agents widely used. These findings suggest that using a MASA primer in resin
      systems has an acceptable biocompatibility for dentin-pulp, involving its
      adsorption and adhesion to hard tooth tissues.

PMID- 1395484
TI  - The effects of various clinical factors on marginal enamel micro-cracks produced
      around composite restoration.
AB  - In this study, enamel micro-cracks produced around composite restorations were
      observed on surfaces and vertical sections, using a stereomicroscope and a
      scanning electron microscope (SEM). The effects of various clinical factors, i.e.
      the curing system, the marginal form and the polishing period after filling, on
      the incidence of marginal enamel micro-cracks were examined. Enamel micro-cracks
      were observed on all of the class 1 and 5 composite restorations when the cavity
      had no marginal bevel and the restorations were polished immediately after
      filling. Enamel micro-cracks distributed approximately parallel to the cavity
      margin and located 0.01-0.3 mm from the restored cavity margin. The occurrence of
      enamel micro-cracks was higher in light-cured composite resin restorations than
      in chemical-cured ones, for non-beveled cavities when polished 10 min or 24 hours
      after filling. The occurrence of micro-cracks was reduced by marginal beveling
      and delayed polishing.

PMID- 1395485
TI  - Three dimensional shape measurement of teeth (2). CAD to produce crown
      considering occlusion.
AB  - Use of a CAD program to design the shape of a crown, restoration of 6 molar was
      studied. Stone models of 5 to 7 molars with 6 prepared die for crown and a
      complete 6 crown which was applied for restoration were measured. The 6 crown
      data were adapted on the 6 die, and adjusted with 5 and 7 proximal teeth. The
      coordinates of the data of 6 were then transferred to that of the 6 die. The ends
      of the adapted crown data were linked with the margin of 6 die. Further the
      occlusal condition with antagonistic tooth was adjusted by applying the FGP
      (functionally generated path) technique. FGP was recorded on bite wax and
      measured. Comparing FGP record and adapted crown, modulation of the occlusal
      surface was accomplished.

PMID- 1395486
TI  - Semi-quantitative analysis of early microleakage around amalgam restorations by
      fluorescent spectrum method: a laboratory study.
AB  - Rhodamine B, a fluorescent substance, was used as a tracer to investigate in
      vitro early microleakage from around amalgam restorations in machinable mica
      glass-ceramic after thermal stress. Five types of amalgam, i.e., low-copper
      spherical, low-copper lathe-cut, high-copper admixture, high-copper lathe-cut,
      and high-copper spherical, were examined in the present study. The results
      indicated that early microleakage from alloys of lathe-cut particles was lower
      than that from alloys of spherical particles in both low-copper and high-copper
      amalgam restorations. A high-copper amalgam with a mixture of lathe-cut and
      spherical particles tended to exhibit the lowest early microleakage.

PMID- 1395487
TI  - Laser-Raman spectroscopic study of the adhesive interface; analysis between 4
      META/MMA-TBB resin and bovine or human dentin.
AB  - A study of the adhesive interface between 4-MET/MMA-TBB resin and hydroxyapatite
      or bovine enamel was reported. The present report is a continuation of that
      study. The possible chemical interaction between 4-methacryloxyethyl trimellitic
      acid (4-MET) and bovine or human dentin was examined by laser Raman spectroscopy.
      A 4-MET monomer solution was prepared by evaporating two thirds of the methyl
      methacrylate (MMA) in a commercial dentin adhesive. The solution was then applied
      to a dentin surface after treating the surface with an aqueous solution of 10%
      citric acid containing 3% ferric chloride. A salt formed on both bovine and human
      dentin surfaces. This salt was formed by the process we previously reported in
      which 4-MET formed a salt on the hydroxyapatite and bovine enamel. No evidence
      was observed of chemical reaction between 4-MET and any organic component in the
      dentin.

PMID- 1395488
TI  - Possibility of allergic reaction to dentin primer--application on the skin of
      guinea pigs.
AB  - We studied the allergic reaction of guinea pigs to glyceryl methacrylate (GM),
      hydroxyethyl methacrylate (HEMA) and meso-erythritol methacrylate (EM), which are
      used as dentin primers. On the 18th day of the application test, when macroscopic
      investigation revealed an inflammatory reaction, the methacrylic acid-treated
      group showed marked eschar formation in comparison with the control group. In
      each of the dentin primer groups, a slight degree of skin redness was noted, but
      there were no serious symptoms. On the 25th day, the applications were resumed
      macroscopic inspection on the 32nd day found eschar in the methacrylic acid group
      only. Therefore, this experiment with dentin primers suggests a delayed allergic
      reaction. Local irritability test showed a more severe reaction than the
      application test. In this test, all experimental dentin primers and methacrylic
      solution promptly showed inflammation, and the chemical compound, methacrylic
      acid was a factor in inflammation.

PMID- 1395489
TI  - Developments of the new instruments for TMJ arthroscopic surgery.
AB  - A large and clearly visible operating area is essential for successful
      arthroscopic surgery of the temporomandibular joint. The keys to a successful
      operation are the safe and accurate positioning of a large scope and multiple
      cannulations, overcoming blind areas. We developed some instruments to resolve
      these problems; i.e., scopes with a large diameter for high resolution, a
      triangulation instrument for multiple cannulations, a needle set-up jig for disk
      traction suture, a step cannulation system and a two-channel cannula for
      operating in the narrow lower joint space and a fixing jig for cannulas in the
      upper and lower joint space to observe the same portion of the discal tissue from
      both joint space during disk suturing. From our experience in applying systematic
      procedures using these instruments in 37 arthroscopic surgeries, it is possible
      for this procedure to be done under a visual field and the surgical time
      considerably shortened.

PMID- 1395490
TI  - Perception of conspecific faces by budgerigars (Melopsittacus undulatus): I.
      Natural faces.
AB  - Perception of faces by 4 budgerigars (Melopsittacus undulatus), a species of
      small parrot, was studied with a same-different discrimination task. Reaction
      times were taken as a measure of the similarity between pairs of faces and
      analyzed with multidimensional scaling to reveal patterns of similarity among the
      faces. The perception of natural faces was tested to determine which
      characteristics were perceptually salient. Color, patterns of markings, darkness
      of the iris, and size of the pupil corresponded to the observed patterns of
      similarity among the faces. Differences among budgerigar faces were more salient
      than differences among zebra finch faces, and budgerigar faces were perceptually
      distinct from the faces of other avian species. The results from these
      experiments provide a basis for understanding the ways in which these signals
      function in the coordination of social behaviors.

PMID- 1395491
TI  - Age and sex as factors influencing spontaneous exploration and object
      investigation by preadult rats (Rattus norvegicus).
AB  - This study examined developmental and sex differences in the exploratory and
      investigatory behaviors of Long-Evans rats (Rattus norvegicus). Littermate
      sextuplets were divided into sex-matched groups (at 30, 60, and 90 days of age)
      and were individually videotaped on 2 consecutive nights in an arena that
      contained stimulus objects. Multiple measures of locomotor exploration and object
      investigation increased significantly with age but were not influenced by sex.
      Older rats entered more quickly, were more active, spent more time in the arena,
      and spent more time investigating inanimate stimulus objects than did younger
      rats. Sex did not significantly affect most measures of open-field behavior;
      however, the data suggest that the sexes may begin to diverge by 90 days. These
      results suggest that preadult rats of both sexes are equipped early in
      development with similar strategies and repertoires for exploration and
      investigation.

PMID- 1395492
TI  - Young children's (Homo sapiens) understanding of knowledge formation in
      themselves and others.
AB  - Three- and 4-year-old children (Homo sapiens) were tested for comprehension of
      knowledge formation. In Experiment 1, 34 subjects watched as a surprise was
      hidden under 1 of 4 obscured cups. The experimenter then pointed to the cup. All
      children searched under the correct cup, but no 3-year-olds (in contrast to most
      4-year-olds) could explain how they knew where to look. Subjects then
      discriminated between simultaneous pointing by 2 adults, one who had hidden a
      surprise and one who had left the room before the surprise was hidden. Most 4
      year-olds (but no 3-year-olds) showed clear discrimination between the adults. In
      Experiment 2, 16 subjects were tested with procedures designed to make the source
      of their own knowledge more obvious, but this had no effect on performance. We
      conclude that studies using very similar procedures with chimpanzees and rhesus
      macaques were measuring an ability (or inability) to understand how knowledge
      states form.

PMID- 1395493
TI  - Perception of cliff swallow calls by birds (Hirundo pyrrhonota and Sturnus
      vulgaris) and humans (Homo sapiens).
AB  - We tested for species differences in the perception of the cliff swallow chick
      begging call. One cliff swallow (Hirundo pyrrhonota), 3 European starling
      (Sturnus vulgaris), and 3 human (Homo sapiens) subjects were trained on go-no-go
      or repeating background tasks to discriminate between all possible stimulus
      pairs, measured by percentage of correct response and latency. We used
      multidimensional scaling to convert the similarity measures into a 2-dimensional
      map for each subject. Most of the maps were significantly correlated in Dimension
      1 but not in Dimension 2. A cluster analysis separated bird and human maps. To
      identify the most important acoustic cues for each subject, we regressed the
      coordinates of each dimension on acoustic variables measured from the stimuli.
      For all subjects, center frequency was Dimension 1. Different acoustic cues were
      associated with Dimension 2, with agreement only on bandwidth, by the cliff
      swallow and 1 starling.

PMID- 1395494
TI  - Conditioned taste and taste-potentiated odor aversions in the Syracuse high- and
      low-avoidance (SHA/Bru and SLA/Bru) strains of rats (Rattus norvegicus).
AB  - Syracuse high- and low-avoidance Long-Evans rats (Rattus norvegicus; SHA/Bru and
      SLA/Bru) were selectively bred for good and poor active-avoidance learning.
      However, SLA/Bru animals are superior to SHA/Bru rats in conditioned suppression
      and passive avoidance learning. In this experiment, saccharin taste and almond
      odor were the components of a compound conditioned stimulus (flavor) in an
      illness-induced aversive conditioning paradigm. SLA/Bru rats (n = 17) showed
      stronger conditioned flavor, taste, and odor aversion than did SHA/Bru animals (n
      = 18). Unselected Long-Evans rats (n = 18) were intermediate between the selected
      strains. SLA/Bru and Long-Evans rats showed taste-potentiated odor aversions in
      this experiment, whereas SHA/Bru animals did not. The results provide evidence
      that genetic factors, as exemplified by the different strains, are importantly
      involved in the mechanisms underlying interoceptive and exteroceptive aversive
      conditioning.

PMID- 1395495
TI  - Affiliative vocalizations in infant rhesus macaques (Macaca mulatta).
AB  - In Experiment 1, infant rhesus monkeys (Macaca mulatta) were separated and then
      reunited with mothers, united with a male, or placed in an empty cage. Infants
      girned more when with mothers or the male than when alone. Girns declined over
      time when infants were united with the male. Coo rates were high when the infant
      was alone or with the male. Shrieks, barks, and fear-related behavior were higher
      with the male. In Experiment 2 the vocalizations of infants were examined during
      separation when alone or when mothers or a male were in the same room. Infants
      cooed more when mothers or a male were present. Cooing increased over time, with
      a greater increase in the mothers' presence. Girns were given to both mothers and
      males, but more were given to mothers. Coos and girns are both affiliative
      vocalizations but are differentially modulated as infants cease cooing when they
      receive contact comfort.

PMID- 1395496
TI  - Sex differences in the incidence and sonographic characteristics of antipredator
      ultrasonic cries in the laboratory rat (Rattus norvegicus).
AB  - Long-Evans rats (Rattus norvegicus; ns = 10 males and 10 females) in a burrow
      system responded to a cat in the open area by retreating to a burrow and emitting
      ultrasounds of 18-27 kHz. Females made more frequent ultrasonic cries, with
      longer durations of ultrasounds. In a 2nd study (ns = 19 males and 19 females),
      sonographic analyses confirmed the more frequent vocalizations of females and
      indicated that the sound pulses of females were reliably shorter in duration and
      of higher base frequency than those of males. Also, females emitted more pulses
      per pulse train with shorter within-train interpulse intervals. Six basic pulse
      forms were determined, and males emitted more (70%) pulses with negatively
      accelerated descending frequencies than females (25%). The findings indicate that
      female rats show qualitatively different antipredator vocalizations than do males
      and add to previous findings of higher levels of female antipredator
      defensiveness.

PMID- 1395497
TI  - Syllable chunking in zebra finch (Taeniopygia guttata) song.
AB  - We examined how 61 young zebra finch (Taeniopygia guttata) males copied song from
      5 adult tutors. Zebra finch song consists of a string of 5-15 distinct syllables,
      and these syllables were copied as chunks, or strings of consecutive syllables
      (modal length = 3). The silent interval between 2 syllables was copied as part of
      the syllable after the silence. Copied chunks had boundaries that fell at
      consistent locations within the tutor's song, marked by a relatively long
      intersyllable silent period, a transition between call-like and noncall-like
      syllables, and a tendency for the tutor male to stop his song short. Young males
      also tended to break their songs off at the boundaries of the chunks they had
      copied. Chunks appear to be an intermediate level of hierarchy in song
      organization and to have both perceptual (syllables were learned as part of a
      chunk) and motor (song delivery was broken almost exclusively at chunk
      boundaries) aspects.

PMID- 1395498
TI  - Proficient performance of a conjunctive, recursive task by an African gray parrot
      (Psittacus erithacus).
AB  - The comprehension skills of an African gray parrot (Psittacus erithacus), Alex,
      were tested on a taks that included a conjunctive condition. For each trial, Alex
      was shown different collections of 7 items, each collection chosen from among 100
      objects of various combinations of shapes, colors, and materials, and he was
      asked to provide (vocally) information about the specific instance of one
      category of an item that was uniquely defined by the conjunction of two other
      categories (e.g., "What color is the [object defined by shape and material]?").
      Other objects exemplified one, but not both, of these defining categories. Alex
      responded with an accuracy of 76.5%, which indicated that he understood all the
      elements in the question, including the conjunctive condition, and that he used
      these elements to guide his search for the one object in the collection that
      provided the requested information.

PMID- 1395499
TI  - Learning to find the opponent: an ethological analysis of the behavior of
      paradise fish (Macropodus opercularis) in intra- and interspecific encounters.
AB  - In Experiment 1, 15 behavior patterns of male paradise fish (Macropodus
      opercularis; n = 72) toward a male conspecific, a male of another species, or no
      stimulus were recorded, both in home and novel situations. In Experiment 2, the
      same behaviors were recorded in a runway, and the same stimuli were used as
      reinforcers in the goal box (n = 18). A typical learning curve was seen when the
      subject found a male paradise fish in the goal box, learning was followed by
      apparent extinction when another species was found in the goal box, and few signs
      of learning were seen when the goal box was empty. Performance of the fish in
      both experiments can be accounted for by a strong aggressive motivation, a less
      strong but clear general curiosity, and habituation to the experimental
      procedure. In contrast to recent assertions in the literature, we conclude that
      aggressive behavior clearly can serve as a reinforcer in an instrumental learning
      situation.

PMID- 1395500
TI  - The inference of evolutionary trees from molecular data.
AB  - 1. Procedures for multiple alignment of sequence data, subsequent phylogenetic
      inference, and testing of the trees derived are presented. 2. The assumptions
      underlying different approaches and the extent to which they are valid are
      discussed.

PMID- 1395501
TI  - The hemoglobins of marine and freshwater fish: the search for correlations with
      physiological adaptation.

PMID- 1395503
TI  - The relationship between amino acid sequences of sperm-activating peptides and
      the taxonomy of echinoids.

PMID- 1395502
TI  - Lactate dehydrogenase in teleosts. The role of LDH-C4 isozyme.
AB  - 1. Lactate dehydrogenase (LDH) occupies an important position in cell metabolism.
      2. Teleosts possess at least three genetic loci coding for lactate dehydrogenase
      subunits, Ldh-A, Ldh-B and Ldh-c. LDH exists in most tissues in several isozymic
      forms. 3. The isozyme LDH-C4 is synthesized predominantly in regions of the
      nervous system concerned with the eye.

PMID- 1395504
TI  - Sperm-activating peptide type-V (SAP-V), a fifth member of the sperm-activating
      peptide family, purified from the egg-conditioned media of the heart urchin
      Brissus agassizii.
AB  - 1. A novel type of sperm-activating peptide named sperm-activating peptide type-V
      (SAP-V) was isolated from the egg-conditioned media (egg jelly) of the heart
      urchin Brissus agassizii and the primary structure of the peptide was determined
      by fast atom bombardment mass spectrometry as follows: Gly-Cys-Glu-Gly-Leu-Phe
      His-Gly-Met-Gly-Asn-Cys. 2. SAP-V and [Met(O)9]SAP-V stimulated the respiration
      of B. agassizii spermatozoa with half-maximal concentrations of 0.5 and 0.3 nM,
      respectively. However, half-maximal stimulation of the sperm respiration required
      40 nM of S-carboxymethylated SAP-V. 3. SAP-V induced significant increases in the
      cyclic AMP and cyclic GMP levels in B. agassizii spermatozoa in a concentration
      dependent manner. 4. The addition of SAP-V to B. agassizii spermatozoa resulted
      in a mobility shift of a major sperm protein (mol. wt from 133,000 to 129,000) on
      sodium dodecyl sulfate-polyacrylamide gels.

PMID- 1395505
TI  - Constitutive protein secretion by guinea-pig seminal vesicle epithelial cells.
AB  - 1. Secretion of pulse-labelled protein by the isolated epithelium of guinea-pig
      seminal vesicle epithelium was rapid, unaffected by cholinergic and adrenergic
      drugs, cyclic nucleotides or changes in the sodium, potassium and calcium
      concentrations of the "chase" medium. 2. Low temperature, NH4Cl, hyper- and hypo
      osmolarity and membrane-stabilizing agents inhibited secretion which was also
      dependent on aerobic metabolism. 3. Monensin reduced secretion of the six
      labelled, relatively low molecular weight proteins recovered from the medium in a
      concentration-dependent, apparently non-specific manner.

PMID- 1395506
TI  - Unsaturated fatty acids inhibit glucocorticoid receptor binding of trout hepatic
      cytosol.
AB  - 1. The effect of free fatty acids [FFAs (saturated (S) and unsaturated (U))] on
      dexamethasone binding in vitro using liver cytosol from rainbow trout was
      examined. 2. All UFFAs but none of the SFFAs tested suppressed binding. This
      suppression is dose-dependent and correlated roughly with the degree of
      unsaturation of the FFAs. 3. Scatchard analysis indicated that the addition of
      linoleic C18:2 (150 microM) increased the dissociation constant (Kd = 5.1 +/- 0.4
      x 10(-8) M vs control of 1.7 +/- 0.3 x 10(-8) M) but minimally affected the
      binding capacity (Bmax = 68 +/- 6.2 vs control of 88 +/- 15.2 fmol/mg protein)
      suggesting C18:2 caused a conformational change of the receptor. 4. Lineweaver
      Burk plot revealed a mixed non-competitive type of inhibition by C18:2. 5. Free
      acid appeared to be required for inhibition as esterification or derivatization
      of the acid greatly diminished its potency. 6.C18:2 also promotes the
      dissociation of bound [3H]-dexamethasone from the steroid-receptor complex but
      slower in rate and lesser in magnitude compared to that caused by dexamethasone
      or the glucocorticoid antagonist RU 38486. 7. UFFAs and some of their derivatives
      can thus modulate glucocorticoid receptor function in vitro and might play
      essential roles in regulating glucocorticoid action in fish as well. 8. These
      fatty acids presumably acts at a site different from that of the glucocorticoid
      binding site.

PMID- 1395507
TI  - Detection of a sperm-coating antigen in the semen of Bubalus bubalis.
AB  - 1. Surface antigens of B. bubalis spermatozoa were solubilized by Triton X-100
      and EDTA; the sperm extract was used to raise antibodies in rabbits. 2. Two major
      polypeptides, immunoprecipitated from the seminal plasma by the antibodies
      against the sperm extract, exhibited the same electrophoretic mobilities of two
      immunorelated sperm surface antigens. 3. The two polypeptides were isolated from
      the seminal plasma, by a multi-step chromatographic procedure, and found subunits
      of a single protein (MW 30,000), called SP 30. 4. The SP 30 protein bound in
      vitro to the postacrosomal region of homologous spermatozoa from cauda
      epididymis. 5. The localization of the sperm-coating antigen on the cell surface
      is compatible with a role in the fertilization process.

PMID- 1395508
TI  - Microsomal ethanol-oxidizing system in Euglena gracilis. Similarities between
      Euglena and mammalian cell systems.
AB  - 1. ADH activity of Euglena grown with 50 mM ethanol decreased, but MEOS activity
      increased with a corresponding increase in the total amount of cytochrome P-450.
      2. Phenobarbital treatment increased the total amount of cytochrome P-450. 3. CO
      and KCN, cytochrome P-450 ligands, diminished acetaldehyde formed from ethanol
      oxidation by MEOS. 4. The amounts of NAD(P)H cytochrome c reductases and
      cytochrome b5 type, components of microsomal monooxygenase reaction, have been
      spectrophotometrically measured. 5. NAD(P)H cytochrome c reductases activities
      were induced by phenobarbital. 6. DMSO, an inhibitor of rabbit MEOS, inhibited O2
      consumption (11-20%) by Euglena grown with an ethanol, but not a lactate medium.
      7. These studies indicate the presence of cytochrome P-450-dependent MEOS in
      Euglena similar to that in the mammalian hepatic cell.

PMID- 1395509
TI  - Serine proteinase inhibitor profiles in the hemolymph of a wide range of insect
      species.
AB  - 1. The inhibition of trypsin, chymotrypsin, neutrophil elastase and cathepsin G,
      and pancreatic elastase by the hemolymph of 14 insect species in six orders has
      been investigated. 2. All samples showed great diversity in terms of both total
      proteinase inhibitory capacity and specificity. 3. The highest total inhibitory
      capacity was found in the larval hemolymph of species in the beetle family
      Tenebrionidae and the lowest in that of an adult coreid bug, Acanthocephala
      femorata.

PMID- 1395510
TI  - A comparison of methods for sample clean-up prior to quantification of metal
      binding proteins.
AB  - 1. The recovery of rabbit metallothionein and metallothionein-like proteins has
      been examined under different conditions. 2. After heat or ethanol denaturation,
      recovery of rabbit MT-II was quantitative. 3. Recovery of rabbit MT was not
      affected by the presence or absence of dithiothreitol (DTT) after heat treatment.
      However, recovery from ethanolic solution decreased in buffers that did not
      contain the antioxidant. 4. Acetone precipitation of rabbit MT resulted in lower
      yields which approached 90% only in the presence of DTT. 5. Recovery of
      metallothionein-like proteins from cytosols of the hepatopancreas of the tanner
      crab, Chionoecetes bairdi, were examined using pulse polarography and HPLC.
      Relative to heat denaturation, ethanol and acetone yielded recoveries of 66 and
      28%, respectively, in the presence of DTT. However, acetone did yield a solution
      which contained less extraneous protein of molecular mass greater than 43 kDa
      than heat denaturation. 6. We concluded that heat denaturation is the preferred
      treatment for quantitative recovery of metal-binding proteins. Acetone
      precipitation is useful for the purification of MT.

PMID- 1395511
TI  - Human liver glutamic gamma-semialdehyde dehydrogenase: structural relationship to
      the yeast enzyme.
AB  - The amino acid sequences of nine tryptic peptides (containing altogether 105
      amino acids) from human liver glutamic gamma-semialdehyde of dehydrogenase
      (hitherto designated as ALDH4) were found to correspond, at 33-66% identity, to
      segments from the yeast 1-proline-5-carboxylate (P5C) dehydrogenase encoded by
      the PUT2 gene.

PMID- 1395512
TI  - Characterization of a G-protein from the mandibular organ of the lobster Homarus
      americanus (Nephropidae, Decapoda).
AB  - 1. GTP-binding activity was found in both calf brain and male lobster mandibular
      organ (MO). There was approximately two to three times as much binding in the
      calf brain. 2. The GTP-binding activity could be extracted from the calf brain
      with sodium cholate, but not from the MOs. 3. Using ADP-ribosylation catalyzed by
      pertussis toxin, GTP-binding was shown to be the result of the presence of G
      protein. In the lobster MO the G-protein alpha subunit has a molecular weight of
      about 42 kDa and may be of the Go or Gi varieties.

PMID- 1395513
TI  - Glutathione mixed disulfides and heterogeneity of chicken hemoglobins.
AB  - 1. Adult chicken hemoglobins Hb A and Hb D interact with glutathione disulfide,
      GSSG. The major hemoglobin, Hb A, forms at least two new components, termed GHb
      AI and GHb AII, and Hb D forms at least one, GHb DI. 2. At pH 8.0 and 5 degrees
      C, glutathione disulfide (GSSG) in a molar excess of 50 x took 6 days to complete
      the reaction, although at pH 8.6 and 41 degrees C only 1 hr was needed, where the
      hemoglobins Hb A and Hb D were converted to their most mobile forms GHb AII and
      GHb DI. 3. Slight molar excess (2.7 GSSG/Hb, pH 7.4, 41 degrees C), reacting for
      1 hr, showed extensive formation of GHb AI and some GHb AII. 4. Electrophoretic
      patterns, from the reaction products of 54 GSSG/Hb excess at different times,
      showed a marked pH dependence. 5. Titration with pCMB (p-chloromercuribezoic
      acid) of DTE (dithioerythrytol)-reduced samples showed 8.0 +/- 0.4 (N = 5) -SH
      (sulfhydryl) per tetramer. In hemolysates not reacted with DTE, 6.0 +/- 0.4 (N =
      3) -SH were detected. 6. DTE-reduced and GSSG-reacted hemoglobins showed 4.6 +/-
      0.5 (N = 7) -SH and 1.5 +/- 0.4 (N = 6) -SH, respectively, as titrated by DTNB,
      pH 8.0. DTE-reduced hemoglobins showed four fast-reacting -SH groups, no longer
      present in GSSG-reacted hemoglobins. 7. Our data indicate that chicken GHb AI and
      GHb DI probably have two glutathionyl residues per tetramer whereas GHb AII has
      four.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395514
TI  - Induction of cystatin S in rat submandibular glands by papain.
AB  - 1. Papain (a cysteine proteinase) were administered into the oral cavity of rats
      twice daily for 5 days. This treatment caused a dramatic increase in the level of
      cystatin S (a cysteine proteinase inhibitor belonging to family 2 of cystatin
      superfamily) in enlarged submandibular glands. 2. Immunochemical analysis using
      antibody against rat cystatin S and electrophoretic analysis confirmed that the
      protein induced by papain was identical to that induced by isoproterenol. 3.
      Induction of the cystatin S in the submandibular glands by oral administration of
      papain suggested a biological response which plays a role in preventing injury
      exogenous proteinase.

PMID- 1395515
TI  - D-glyceraldehyde-3-phosphate dehydrogenase from HeLa cells--1. Purification and
      properties of the enzyme.
AB  - 1. D-GPDH from HeLa cells was isolated and purified. 2. Some basic kinetic
      constants are reported. 3. Sodium dodecyl polyacrylamide gel electrophoresis gave
      a single band with a molecular weight of approximately 36 K. 4. ATP and NADH
      inhibit competitively enzyme activity. 5. Comparative catalytic properties of
      GPDH from normal and tumor cells were effectuated.

PMID- 1395516
TI  - Genetic differences in steroid-induced protein synthesis in vivo of the liver and
      magnum in immature chicks (Gallus domesticus).
AB  - 1. The present study was conducted to investigate whether or not the rate of
      steroid-induced protein synthesis measured in vivo in the liver and magnum was
      different between chicks from different genetic backgrounds. 2. Both protein
      deposition and synthesis in the liver were enhanced after the administration of
      beta-estradiol with or without testosterone. In the magnum, the combined
      administration of beta-estradiol and testosterone resulted in significantly
      higher protein deposition and synthesis than did beta-estradiol alone. 3. After
      the administration of beta-estradiol and testosterone, protein deposition in the
      liver and magnum was lower in broiler than in layer and dual-purpose chicks.
      Protein synthesis in the magnum tended to be highest, though not significantly,
      in layer, followed by dual-purpose and broiler chicks in decreasing order. 4.
      Steroid-induced protein deposition in the liver was not changed between chicks
      genetically selected for low and high albumen contents. In contrast, steroid
      induced protein synthesis in the magnum was significantly higher in high-albumen
      birds than low-albumen chicks. 5. It was concluded that genetic traits for high
      egg production were well reflected in increased protein deposition and synthesis
      in the liver and especially in the magnum of immature female chicks stimulated by
      steroid hormone treatment.

PMID- 1395517
TI  - Isolation and partial characterization of serine- and threonine-rich porcine
      gastric mucus glycopeptides.
AB  - 1. Two subfractions from purified porcine gastric mucus glycopeptide were found
      to separate from each other by cesium chloride equilibrium centrifugation. The
      highest density fraction and two lower density fractions separated were
      designated VHD, HD and LD, respectively. A comparative study of these components
      was made. 2. The high and low density fractions, HD and LD, appeared almost the
      same or identical, while VHD differed completely from either of them in the
      following respects: (1) VHD exhibited strong alcian blue binding activity. (2)
      57% of VHD bound to the DEAE-Toyopearl column equilibrated with 0.2 M NaCl. (3)
      VHD eluted from the Sephacryl S-400 column as a lower molecular subunit. (4) One
      third of the sialic acid as a minor component in VHD was constituted by N
      glycolylneuraminic acid. (5) Carbohydrate composition showed typical mucus
      glycoprotein with slightly higher fucose content. (6) Amino acid compositions of
      the anionic components prepared from VHD showed the highest Ser/Thr ratio, 1.92
      compared to 0.46 for LD and 0.62 for HD. (7) Oligosaccharide released from VHD by
      alkaline-sodium borohydride treatment was larger than that from HD or LD. 3. The
      above results indicate the minor component, VHD, separated from the major
      components, to be a quite similar but not identical component to the so-called
      sulfated mucus glycoprotein reported previously [Slomiany et al. (1972) J. biol.
      Chem. 247, 5062-5070].

PMID- 1395518
TI  - The amino acid sequence of the single hemoglobin of the high-antarctic fish
      Bathydraco marri Norman.
AB  - 1. Bathydraco marri Norman is a cold-adapted Antarctic teleost (Family:
      Bathydraconidae), living preferably at depths between 400 and 1200 m. 2. The
      blood of this species contains a single hemoglobin, in which oxygen binding is pH
      regulated (Bohr and Root effects). 3. The complete amino acid sequence of the
      alpha and beta chains of the hemoglobin of B. marri has been elucidated.

PMID- 1395519
TI  - Further studies on semicarbazide-sensitive amine oxidase activities (SSAO) of
      white adipose tissue.
AB  - 1. White adipose tissue (WAT) from mice, rabbits, pigs and human subjects was
      investigated for the characterization of the tissue-bound semicarbazide-sensitive
      benzylamine oxidase activities (SSAO) present in each species. 2. Enzymes from
      mice, rabbits and pigs shared similar biochemical characteristics: they exerted
      histaminase activity, oxidized methylamine and acetylputrescine and were
      completely blocked by carbonyl reagents and by 3,5-ethoxy-4-aminomethylpyridyne
      (B24), in a dose-dependent fashion. 3. SSAO activity from human WAT had a lower
      affinity for benzylamine compared with enzymes in the other species and did not
      show any histaminase activity. 4. These results show that SSAO from human tissues
      might have different properties from SSAO of other species.

PMID- 1395520
TI  - System identification for the ECG using CZT.
AB  - A new approach for extraction of clinically useful parameters from the ECG signal
      is presented using the system identification technique of CZT on the DCT
      transformed signal. A one to one relationship between the model singularities and
      the significant points in the time signal is arrived at. The method allows the
      determination of R-R interval needed in rhythm analysis. The complex cepstrum is
      used for identifying and removing the effect of zeros outside the unit circle. A
      significant data compression of 1 in 10 is achieved. A large number of continuous
      strips of ECG data are analyzed and the results are presented.

PMID- 1395521
TI  - An approach to the generalized nurse scheduling problem--generation of a
      declarative program to represent institution-specific knowledge.
AB  - An approach to the nurse scheduling problem is presented. The critical problem in
      nurse scheduling in a hospital is how to determine the day-to-day shift
      assignments of each nurse for a specified period in a way that satisfies the
      given requirements as much as possible, where the requirements differ greatly
      depending on the hospital. We present a method for constructing an agency
      independent core procedure which can be tailored to the peculiar requirements of
      an individual hospital. As a basis, a formal analysis of the problem was
      performed, and a general scheduling procedure was established. Based on the
      method, a software system which produces a scheduling program for a given
      institution was developed. A declarative program that represents institution
      specific information is generated through an interview with the user and
      incorporated into the general procedure. Some of the programming technicalities
      and an application of the system are also presented.

PMID- 1395522
TI  - Dimensions of knowledge sharing and reuse.
AB  - Many workers in medical informatics are seeking to reuse knowledge in new
      applications and to share encoded knowledge across software environments.
      Knowledge reuse involves many dimensions, including the reapplication of
      lexicons, ontologies, inference syntax, tasks, and problem-solving methods.
      Principal obstacles to all current work in knowledge sharing involve the
      difficulties of achieving consensus regarding what knowledge representations
      mean, of enumerating the context features and background knowledge required to
      ascribe meaning to a particular knowledge representation, and of describing
      knowledge independent of specific interpreters or inference engines. Progress in
      the area of knowledge sharing will necessitate more practical experience with
      attempts to interchange knowledge as well as better tools for viewing and editing
      knowledge representations at appropriate levels of abstraction. The PROTEGE-II
      project is one attempt to provide a knowledge-base authoring environment in which
      developers can experiment with the reuse of knowledge-level problem-solving
      methods, task models, and domain ontologies.

PMID- 1395523
TI  - Computer probability estimates of angiographic coronary artery disease:
      transportability and comparison with cardiologists' estimates.
AB  - A computer algorithm for estimating probabilities of any significant coronary
      obstruction and triple vessel/left main obstructions was derived, validated, and
      compared with the assessments of cardiac clinician angiographers. The algorithm
      performed at least as well as the clinicians when the latter knew the identity of
      the patients whose angiograms they had decided to perform. The clinicians were
      more accurate when they did not know the identity of the subjects but worked from
      tabulated objective data. Referral and value induced bias may affect physician
      judgment in assessing disease probability. Application of computer aids or
      consultation with cardiologists not directly involved with patient management may
      assist in more rational assessments and decision making.

PMID- 1395524
TI  - Tolerating spelling errors during patient validation.
AB  - Misspellings, typographical errors, and variant name forms present a considerable
      problem for a Clinical Information System when validating patient data.
      Algorithms to correct these types of errors are being used, but they are based
      either on a study of frequent types of errors associated with general words in an
      English text rather than types of errors associated with the spelling of names,
      or on errors that are phonologically based. This paper investigates the types of
      errors that are specifically associated with the spelling of patient names, and
      proposes an algorithm that effectively handles such types of errors. This paper
      also studies the effectiveness of several relaxation techniques and compares them
      with the one that is being proposed.

PMID- 1395525
TI  - User and manufacturer's requirements for IMAC standardization in Japan.
AB  - Many radiologists and radiological technologists understand that Picture
      Archiving and Communication Systems (PACS) are useful not only for image
      management but also for improving the quality of patient care. However, such
      systems have not yet been widely installed in hospitals. In order to determine
      why radiologists have not installed a PACS in their hospitals, we carried out a
      written survey of 400 Japanese hospitals asking them to describe the current
      image management activities, the problems inherent in PACS and the problems
      related to standardization. 216 hospitals responded, and the following
      suggestions were compiled concerning possible improvements to PACS. (1) PACS
      benefit needs to be improved with respect to patient care. (2) The cost of PACS
      should be reduced. (3) The system should be easier to operate and should save
      time. (4) Standardization is needed to allow simplified, cost-effective
      networking. We also carried out a written survey of 25 PACS and related equipment
      manufacturers asking them to describe the opinions inherent in current PACs and
      the problems related to standardization. Ten manufacturers responded, and the
      various suggestions were compiled concerning possible improvements to the PAC
      system.

PMID- 1395526
TI  - Influence of CRT workstation on observer's performance.
AB  - The effects of the operability of the prototype CRT workstation and room
      illumination upon observer's performance were studied. In the experiment of
      reading CT images as a routine daily work at the CRT workstation, the average
      time required to analyse one CT image under a room illuminance of 100 lux was
      longer than that on the film viewbox. Prolongation occurred due mainly to the
      longer time required to retrieve and to arrange images as observers desired, and
      the limitation to the number of images simultaneously displayed on two CRT
      monitors. In the ROC studies to detect small pulmonary nodules on CRT images of
      computed radiography with imaging plate, illuminance around 170 lux showed the
      best result and a statistically significant difference (P less than 0.05) as
      compared with that of 480 lux. In addition to the radiologist's visual
      performance, room illumination must also be taken into consideration as it
      influences the observer's performance and diagnostic efficiency.

PMID- 1395527
TI  - The use of multimedia in patient care.
AB  - A personal computer based system was constructed to assess the use of various
      forms of information (multimedia) in patient record keeping. A patient's file
      with his records kept in a multimedia fashion was made by using the system. We
      describe the hardware and software construction of the system together with the
      results and the memory requirements of each type of media. Potential usage of the
      system in the future is discussed especially in connection with the Picture
      Archiving and Communications Systems (PACS).

PMID- 1395528
TI  - Nordic teleradiology development.
AB  - In the Nordic countries there are several reasons why teleradiology has been an
      interesting topic of research during the last years. The distances in rural areas
      are long, and radiology expert service is not available in every health centre
      which is able to provide X-rays. Also, the telecommunication network is on a very
      advanced level in the Nordic countries. The staff is well educated and they are
      used to operating with computers. This all means that the infrastructure to
      develop and use systems like teleradiology exists. This paper describes two
      separate systems developed in Norway and Finland. Their development has been in
      many respects the same. The common hardware and software features, as well as the
      differences and the clinical experiences, are discussed in this paper.

PMID- 1395529
TI  - PACS in the new Skejby Hospital.
AB  - A radiology department with digital imaging equipment and a decentralized PACS
      has been planned, and is under installation in the new university hospital-
      Skejby Sygehus--in Arhus, Denmark. The background for the decision, the planning
      procedure and details of the plan are described.

PMID- 1395530
TI  - Experience of a small PACS in Tottori University Hospital.
AB  - Picture archiving and communications systems (PACS) are expected to become
      feasible as the way of total radiologic image management. As the first step
      towards computerized image management, we installed an experimental small PACS
      with a digital optical archive for magnetic resonance and digitized radiographic
      film images. During the first 10 months of operation, problems were caused by the
      frequent mechanical troubles on the acquisition devices, impractical schemes for
      transmission, and troublesome retrieval and display of images. Although some of
      them have been solved by the improvements of both hardware and software, the
      mechanical instability of the digitizer and the inadequate operating procedure of
      the workstation still remain. As to the characteristics of PACS, the capability
      of access to every achieved radiologic image is the great advantage for us
      because the image integration has been impossible in the form of radiographic
      films for the traditional image management system of our hospital. However, the
      complicated image display procedure with high overheads is far from ideal for
      radiologists. The efficiency of image display must be increased to the level of a
      conventional film viewing system. Furthermore, research is needed on the small
      PACS to get consensus for the acceptance of a more widely implemented system.

PMID- 1395531
TI  - Digital/analog hybrid system for filing of endoscopic images.
AB  - A new system was developed for filing all the endoscopic images generated in our
      hospital. The system is composed of an on-line network for analog images supplied
      from the endoscopy stations and stored on 300 mm optical disks, on the one hand,
      and an off-line PACS for digital images recorded on a 130 mm magneto-optical disk
      (MOD) at each endoscopy station, on the other. For close examination of the
      images digital images are displayed from the MOD on a high-resolution computer
      graphic monitor, and for quick review of a large number of images, analog images
      are retrieved from the 300-mm optical disks. This system has been in clinical use
      at our university hospital for the past year and has proven useful for education
      of endoscopy, for the quality control of the endoscopy practice, and for the
      management of the patients.

PMID- 1395532
TI  - Information compression in dynamic radiological studies.
AB  - The large volumes of digital image data from radiological examinations demand
      further research and practical solutions in image compression before PACS
      solutions in large radiological departments are plausible. But another type of
      compression of image information is also possible, which has, in fact, been
      somewhat utilized already in analog form, but which has far better possibilities
      in the digital world. The number of essential images in dynamic X-ray, nuclear
      medicine, examinations etc. can be greatly reduced. These examinations producing
      image series are reviewed in terms of compression of information. 3-D displays
      are very useful in slice imaging, because they provide a means to see easier
      inside the human body than a number of slice images side by side. We also provide
      a new method, dynamic pulmonary imaging with digital fluoroscopy, as an example
      of the digital possibilities to compress a number of images into parametric
      images, numbers, histograms and curves. These processes also have other positive
      consequences information is transformed into a more easily perceptible form.

PMID- 1395533
TI  - Review of the American College of Radiology--National Electrical Manufacturers'
      Association standards activity.
AB  - The American College of Radiology and the National Electrical Manufacturers'
      Association published the ACR-NEMA Digital Imaging and Communications Standard in
      1985. Implementations are just now becoming available. During this time, working
      groups of the committee responsible for the standard have been very active. An
      expanded version of the standard was published in 1988 and a third version, to be
      known as Digital Imaging and Communications in Medicine (DICOM), is being
      prepared for publication in 1992. This paper briefly reviews the history of the
      standard, describes recent activities, outlines the extensions planned for the
      DICOM standard, and describes the participation of the committee in international
      radiological imaging standards activities.

PMID- 1395534
TI  - Standardization of network addressing in picture archiving and communications
      systems utilizing the ISO OSI protocols.
AB  - The establishment of a communications network requires the definition of
      addressing schemes to identify systems attached to the network. When it is
      anticipated that such a network will interconnect to, or communicate with, other
      similar networks it is beneficial to define standardized addressing schemes. This
      paper discusses the need for the standardization of network service access point
      (NSAP) addresses in picture archiving and communications systems (PACS) which use
      the open systems interconnect (OSI) communications protocols. Possible methods
      for establishing the necessary hierarchy of address registration authorities are
      discussed, along with the corresponding address formats.

PMID- 1395535
TI  - Current status of Image Save and Carry (IS&C) standardization.
AB  - Image Save And Carry (IS&C) was planned to be an off-line information system for
      transmission and exchange of medical images and information between a medical
      facility's different divisions as well as between other hospitals. The IS&C
      committee defines file format for magneto-optical disk, the data format and
      representation, media compatibility and data security and technological
      assessment. A 'zone management method' which contributes to a rapid access of
      data in the recording media is used for IS&C file management. The IS&C standard
      holds as much conformation as possible in order to coordinate with ACR-NEMA
      (American College of Radiology-National Electrical Manufacturers' Association)
      and MIPS (Medical Information Processing Systems) standards. The IS&C data format
      is based upon the ACR-NEMA/MIPS standard. A major difference between the ACR
      NEMA/MIPS standard and IS&C standard is that the IS&C standard is expected to
      serve for recording all kinds of medical information (e.g., diagnostic reports,
      endoscopic images and electrocardiograms), including X-ray images. Applications
      to PACS, teaching files, personal electronic health and medical records are
      promising. The booklet of IS&C standard will be published in the spring of 1992
      by the IS&C committee.

PMID- 1395536
TI  - Oral diagnostic reporting and synchronized image filing using magneto-optical
      disks.
AB  - An experimental radiologic reporting system has been developed and tested. The
      rewritable and compact magneto-optical disk (MOD) is applied to storing medical
      images with oral diagnostic reports of these radiologic images. The disk is 5.25
      inches in diameter, has 600 MB memory capacity, is erasable, light and compact.
      Advantages are simultaneous recording of radiologic images and their oral reports
      by radiologists, and application to circulation of media inside the hospital as
      well as to filing of medical images. The MOD has a multimedia function of
      communication and filing. When medical images are taken and stored, oral
      interpretation by radiologists can be simultaneously added. Physicians can get
      information of the images and their reports by oral speech at the same time in
      front of computer workstation. Furthermore, integration of a voice recognition
      capability is now being undertaken.

PMID- 1395537
TI  - The European Community: standardization in medical informatics and imaging.
AB  - The use of informatics and telecommunications in health care and medicine has
      reached a stage where the application of standards is an absolute requirement.
      The AIM Programme of the CEC DGXIII stimulated the study of the subject, and has
      supported the set up of an official European platform for standardization in this
      field, the CEN TC251. The needs for standardization in one of the subareas,
      medical imaging, are described in detail. The future solutions of the problems
      concerned are regarded prerequisites for the general and practical use of PACS
      and IMACS.

PMID- 1395538
TI  - JPEG compression for PACS.
AB  - In the medical field, especially in diagnostic radiology, there still remains
      controversy over how and whether or not to compress X-ray images for storage and
      transmission. The joint Photographic Expert Group (JPEG) standard which has
      recently been agreed upon is the very attractive technique to archive and to
      transport images in medical fields. This technique is based on 'lossy'
      compression of images, which can handle not only X-ray images but also full
      colored images, and is suitable for introduction into picture archiving and
      communicating systems (PACS). The images can be handled after compression as
      quite small clusters of data. For example, a single 2000 x 2000 x 12 bits chest X
      ray image which is an 8 Mbyte image compressed at a 10:1 ratio could retain
      virtually all the visible quality of the original version, and would take 100 s
      to transmit at 64 kbits/s using the Integrated Services Digital Network (ISDN,
      800 kbytes compressed file, 8 kbytes/s transmission theoretically). An important
      factor in the design of this technique is that this format relies on no specific
      hardware or software if using JFIF (JPEG File interchange Format). Soon this
      algorithm will be able to run on any workstation or on any PC in the world.
      Highly compressed images may be unsuitable for diagnostic purposes. However, they
      may be sufficient for reference images which will be needed in clinical fields.

PMID- 1395539
TI  - [An analysis of recuperating experience by Nightingale's ideas on disease].

PMID- 1395540
TI  - [An introduction to Nightingale's nursing].

PMID- 1395541
TI  - [Beginning course of English medical terminology based on analytical method].

PMID- 1395542
TI  - [Case study reports, No. 19].

PMID- 1395544
TI  - [Asking about 'nursing and medicine'].

PMID- 1395543
TI  - [Human movement and nursing].

PMID- 1395545
TI  - [The world of Hildegard von Bingen].

PMID- 1395546
TI  - [Searching for logic of children's recognition].

PMID- 1395547
TI  - [What is psychiatry?].

PMID- 1395548
TI  - Neuropsychological screening in the psychiatric emergency room.
AB  - In a pilot study, a neuropsychological minibattery of tests consisting of Trail
      Making Test A (TMA), Trail-Making Test B (TMB), and the Visual Reproduction
      subtest (VR) of the Wechsler Memory Scale was administered to patients with
      common psychiatric diagnoses in a psychiatric emergency room (ER). Patients with
      adjustment disorders were not distinguishable from normal controls, while
      patients with affective disorders and schizophrenia were more impaired than both
      of these samples. It is suggested that this or a similar minibattery of tests can
      be of use as an adjunct screening device for differential diagnosis of adjustment
      disorder versus more serious psychopathology in psychiatric ERs.

PMID- 1395549
TI  - Mixed neurologic and psychiatric disorders: pharmacological issues.
AB  - The number of patients with mixed neurologic and psychiatric disturbances is
      large. The psychiatric disturbances are often atypical in presentation and fit
      poorly into standard psychiatric nomenclature. They can be difficult to treat
      using standard psychopharmacologic approaches. This report reviews the impact of
      brain dysfunction on the use of conventional and nonconventional psychotropic
      agents in this mixed population.

PMID- 1395550
TI  - Personality and treatment response in agoraphobia with panic attacks.
AB  - The present study investigated the association of specific personality
      characteristics with agoraphobia, and whether they predicted long-term outcome
      following a group cognitive behavior therapy program. Thirty-three patients with
      agoraphobia with panic attacks, 18 with social phobia, and 26 "normals" were used
      in the study. Personality factors were measured with the Maudsley Personality
      Inventory (MPI), the Hostility and Direction of Hostility Questionnaire (HDHQ),
      and the Fundamental Interpersonal Relations Orientation-Behavior Scale (FIRO-B).
      The results showed that (1) agoraphobics are more extroverted and more likely to
      include others in their activities than are social phobics; however, they are
      less extroverted, more neurotic, more hostile and intropunitive, and less likely
      to include others in their activities than are normals; (2) social phobics are
      similarly less extroverted, more neurotic, and more hostile and intropunitive
      than normals, but, in addition, are less likely to exert control over others,
      more likely to want to be controlled, and less expressive of affection than
      normals; and (3) personality characteristics did not predict treatment outcome.

PMID- 1395551
TI  - Bilateral transfer deficit in schizophrenia.
AB  - Right-handed chronic schizophrenics, left-handed normals, and right-handed
      normals were tested on a measure of bilateral transfer of motor skill in
      contralateral hands. Schizophrenics compared with normals showed significantly
      poor bilateral transfer of skill in terms of errors committed; the group
      difference was nonsignificant in terms of response time. Results suggested a
      breakdown in perceptual-motor coordination in schizophrenia.

PMID- 1395552
TI  - Development, use, and factor analysis of a self-report inventory for mania.
AB  - This report describes the development and initial psychometric evaluation of a 47
      item self-report inventory for mania developed by the authors. Twenty-five
      subjects with a diagnosis of mania and 82 subjects with other diagnoses were
      tested during a hospital admission. The manic group scored significantly higher
      than the nonmanic group. The questionnaire correctly classified 71% of subjects.
      Manic patients who lacked insight endorsed as many items as manic patients with
      insight. A reliability analysis indicated that the items comprising the
      questionnaire are homogeneous. Test-retest reliability was high. A rotated factor
      analysis produced two factors, energized dysphoria and hedonistic euphoria. The
      authors discuss diagnostic, research, and clinical implications and applications
      of the Self-Report Manic Inventory.

PMID- 1395553
TI  - The relationship between social alienation and disorganized thinking in normal
      subjects and localized cerebral glucose metabolic rates assessed by positron
      emission tomography.
AB  - This study investigated the relationships between the relatively mild
      manifestations in verbal behavior of social alienation and disorganized thinking
      in normal subjects and cerebral glucose metabolic rates measured by positron
      emission tomography (PET). Three groups of 10 young normal male subjects were
      injected with D-[18F]deoxyglucose (FDG) during either wakefulness, rapid eye
      movement (REM), or non-REM (NONREM) sleep, and 32 to 45 minutes later they were
      asked to report their thoughts, emotions, or dreams and free-associations to
      these mental events. Nonparametric correlations were obtained between measures of
      interpersonal social alienation, intrapsychic conflicts, and thought disorder
      derived from the typescripts of these reports by content analysis--using the
      Gottschalk-Gleser Social Alienation-Personal Disorganization Scale--and regional
      cerebral glucose metabolic rates obtained from PET scans. Total social alienation
      personal disorganization scores obtained from the reports of wakeful, silent
      mentations showed significant positive correlations with glucose metabolic rates
      in the left temporal lobe. The patterns of significant correlations involving
      these verbal behavior measures derived from the content analysis of verbal
      reports of dreams or other mental events occurring during REM and non-REM sleep
      were in different cerebral locations from those found with these variables during
      silent, waking mentation. Previous observations suggesting that increased left
      temporal lobe glucose may typify chronic schizophrenia may instead be indicative
      of a wide range of thought disorder and/or social alienation manifestations
      occurring, at times transiently and minimally, in normal people.

PMID- 1395554
TI  - Shoplifting in bulimia nervosa.
AB  - This study compared the shoplifting patterns of 27 bulimic and 25 nonbulimic
      shoplifters. Bulimic shoplifters often stole food, but usually also stole other
      items. Nonbulimic shoplifters reported starting to steal at an earlier age,
      weighed more than bulimic shoplifters, and were more likely to endorse antisocial
      reasons for shoplifting.

PMID- 1395555
TI  - Assessing need for extended psychiatric hospitalization.
AB  - The authors developed a set of rating scales to assess a wide range of variables
      believed by clinicians to influence the optimal length of hospital stay. They
      report the results of interrater reliability studies, a factor analysis of the
      scales, and a correlational study of the factors with actual length of stay. They
      describe the potential applications of the scales to clinical practice and
      research.

PMID- 1395556
TI  - A case of monthly unipolar psychotic depression with suicide attempt by self
      burning: selective response to bupropion treatment.
AB  - A second case of monthly, unipolar, psychotic depression is presented, involving
      a 26-year-old woman whose illness had a postpartum onset, recurred premenstrually
      for 33 consecutive months, and involved a suicide attempt by self-burning.
      Whereas various antidepressant, antipsychotic, and hormonal treatments were
      ineffective, bupropion (together with low-dose trifluoperazine) induced an
      immediate and complete remission that was maintained at a 16-month evaluation.

PMID- 1395557
TI  - Patch testing with frullania during a 10-year period: hazards and complications.
AB  - Contact dermatitis from frullania mainly affects people living in the country.
      The 2 most frequent species in Europe, Frullania dilatata and Frullania
      tamarisci, do not cross-react: both species must be patch tested when frullania
      intolerance is suspected. Yet patch testing with frullania may be hazardous: 9
      out of 37 cases recorded in Strasbourg correspond to active sensitization by the
      tests. Since routine testing is risky, only aimed testing can be recommended.

PMID- 1395558
TI  - Reactive changes in human epidermis following simple occlusion with water.
AB  - Reactive changes produced in human epidermis by occlusion with water for 24 or 48
      h were studied. A focally widened intercellular space was common. Several, often
      pronounced, reactive events were observed in the Langerhans cell system, whereas
      the keratinocytes and the melanocytes seemed unaffected. The reactive events
      showed a scattered distribution and were revealed only by electron microscopic
      analysis of extensive section series. It seems that, among epidermal cells, the
      Langerhans cells are the most susceptible and most easily alerted by an exogenous
      challenge.

PMID- 1395559
TI  - Allergic contact dermatitis in shiitake (Lentinus edodes (Berk) Sing) growers.
AB  - A 42-year-old female shiitake grower was investigated to clarify the etiology of
      skin lesions which developed during the planting of shiitake hyphae into bed
      logs. She complained of repeated eczematous skin lesions during the planting
      season, from March to July, for 10 years. She handled 7,000 pieces of small conic
      blocks made of beech, with shiitake hyphae attached to their surface, per day,
      and 300,000 pieces altogether per season. She was positive on patch testing with
      extracts of shiitake hyphae. In contrast, female shiitake growers with skin
      lesions associated with work other than planting, and without skin lesions, were
      negative on patch testing to the hyphae. Moderate allergenicity was observed to
      extracts of shiitake hyphae in a guinea pig maximization test. These findings
      indicated the etiology of skin lesions in shiitake growers to be allergic contact
      dermatitis induced by shiitake hyphae.

PMID- 1395560
TI  - Patch test reactions in atopic patients.
AB  - Patch testing was carried out in 851 atopic patients; 181 atopic dermatitis (AD)
      patients were additionally tested with 50% dilutions of the test substances. The
      occurrence of allergic and irritant reactions was frequent, being 57% and 33% for
      AD patients aged 28-41 years and 19-27 years, respectively. Among age-matched
      allergic rhinitis (AR)/allergic conjunctivitis (AC) or asthma (A) patients, the
      number of allergic reactions varied from 25 to 30%, and for irritant reactions
      was 24%. In all groups, nickel, fragrance-mix, balsam of Peru and neomycin were
      the commonest allergens. Contact allergy to ingredients of topical medicaments
      was common among AD patients and patients with severe and long-lasting dermatitis
      were most frequently sensitized. However, sensitivity to multiple substances was
      not common among those patients. The number of irritant reactions was
      considerable, but 50% dilution of the test substances did not solve the problem.

PMID- 1395561
TI  - The influence of topical dermatological treatment modalities on epidermal
      Langerhans cells and contact sensitization in mice.
AB  - The influence of the widely used topical dermatological treatment modalities
      anthralin, coal tar and pyrogallol on surface markers of epidermal Langerhans
      cells and contact sensitization was studied and compared with that of a PUVA
      treatment. A common effect of all dermatological therapies tested was inhibition
      of Langerhans cell ATPase, whereas an effect on MHC class II antigens was found
      only after PUVA or tar treatment. The induction of contact hypersensitivity was
      inhibited only by PUVA, and not by the other treatments. These results show that
      various forms of topical therapy influence surface markers and immunological
      function of epidermal Langerhans cells differently.

PMID- 1395562
TI  - Diaper dermatitis: a study of contributing factors.
AB  - A 44-week clinical study was carried out on a large sample of the Italian infant
      population to measure the incidence of diaper (napkin) dermatitis and to identify
      the factors related to the development of diaper dermatitis. Factors such as age,
      sex, the presence of atopic dermatitis, the general state of health of the child,
      the use of drugs and the type of diaper used were recorded. At the end of the
      test, 2169 clinical dermatological examinations were performed. The frequency of
      episodes of diaper dermatitis was 15.2%. Statistical correlations between diaper
      dermatitis and age, presence of atopic dermatitis, and health conditions were
      found.

PMID- 1395563
TI  - The sensitizing capacity of the antioxidants propyl, octyl, and dodecyl gallate
      and some related gallic acid esters.
AB  - 8 alkyl gallates, including the widely used antioxidants propyl, octyl, and
      dodecyl (= lauryl) gallate, have been subjected to experimental sensitization in
      guinea pigs. Using a modern sensitization procedure, the results showed that all
      gallates are moderate to strong contact sensitizers: dodecyl (= lauryl) gallate
      was found to be the strongest. A characteristic correlation between side chain
      length and mean response was observed, giving a maximum of sensitization at a
      length of 12 carbon atoms (dodecyl gallate). A literature review revealed that
      the frequency of reports of allergic contact dermatitis from antioxidants of the
      gallate type has increased in the last 4 years. In most cases, the moderate
      sensitizer propyl gallate was the source of sensitization.

PMID- 1395564
TI  - Prick and use tests with 6 glove brands in patients with immediate allergy to
      rubber proteins.
AB  - 20 patients with contact urticaria from rubber gloves were prick tested using
      eluates from 4 latex (Triflex, Ansell Gammex, Exona, Armi) and 2 non-latex
      (Tactylon, Elastyren) glove brands. All patients showed a positive prick test
      reaction to at least 2 latex glove eluates. A hypoallergenic glove (Ansell
      Gammex) gave a positive prick test reaction in 1 patient, but non-latex gloves
      were negative in all cases. All patients showed a positive result in the use test
      with a latex surgical glove (Triflex), whereas none did with a non-latex glove
      (Tactylon). Non-latex gloves and, in some cases, also hypoallergenic latex
      gloves, are a good alternative to rubber gloves for patients with immediate latex
      allergy.

PMID- 1395565
TI  - Contact dermatitis from a billiard cue.

PMID- 1395566
TI  - Allergic contact dermatitis from triphenyl phosphate.

PMID- 1395567
TI  - Contact urticaria due to eucalyptus pollen.

PMID- 1395568
TI  - Radiodermatitis from iridium-192 exposure and allergic contact dermatitis.

PMID- 1395569
TI  - Allergy to castor oil and colophony in a wart remover.

PMID- 1395570
TI  - Allergic contact dermatitis from nickel in an electrocautery plate.

PMID- 1395571
TI  - Occupational allergic contact dermatitis and anaphylaxis from rubber latex.

PMID- 1395572
TI  - Allergic contact hand dermatitis from hydrangea: report of a 10th case.

PMID- 1395573
TI  - Facial contact dermatitis due to black rubber.

PMID- 1395574
TI  - Contact dermatitis from colophony in a horticulturalist.

PMID- 1395575
TI  - Colophony in paper as a cause of hand eczema.

PMID- 1395576
TI  - Contact dermatitis due to resorcinol in a radiotherapy dye.

PMID- 1395577
TI  - Nickel sensitization and atopy.

PMID- 1395578
TI  - Lichenoid dermatitis caused by epoxy resin.

PMID- 1395579
TI  - Contact dermatitis due to topical retinoic acid.

PMID- 1395580
TI  - Contact dermatitis from cuttlefish.

PMID- 1395581
TI  - Immediate wheal after topical administration of chlorproethazine.

PMID- 1395582
TI  - Oral lichen planus from colophony.

PMID- 1395583
TI  - Generalized contact dermatitis from vitamin E.

PMID- 1395584
TI  - Allergic contact dermatitis due to sulconazole.

PMID- 1395585
TI  - Contact allergy to cocamidopropyl betaine (CAPB).

PMID- 1395586
TI  - Patch test reactions and clinical disease.

PMID- 1395587
TI  - Contact dermatitis from diisocyanates.

PMID- 1395588
TI  - Human irritant response to different qualities and concentrations of
      cocoamidopropylbetaines: a possible model of paradoxical irritant response.
AB  - Cocoamidopropylbetaines are surfactants frequently used in cosmetics. We have
      evaluated the irritant capacity of 3 different qualities of
      cocoamidopropylbetaine, using the following method: patch tests have been carried
      out with 5 different dilutions in 67 patients and the results read at 2 days by
      noninvasive methods (direct visualization, transepidermal water loss (TEWL),
      laser Doppler flowmetry (LDF)). The results with the 3 methods were concordant.
      However, the results with the different concentrations were paradoxical, as
      irritancy did not increase at higher concentrations. We have tried to explain
      this by the fact that these substances contain by-products (free amidoamine and
      sodium monochloroacetate), the concentrations tested all being above the critical
      micelle concentration and therefore containing both micelles and monomer.
      Finally, we believe that noninvasive methods such as TEWL and LDF could be of
      great use in the evaluation of irritant contact dermatitis.

PMID- 1395589
TI  - Occupational and non-occupational allergic contact dermatitis from beryllium.
AB  - There are various references to sensitization to beryllium in the literature.
      Since introducing a patch testing series for patients with suspected
      sensitization to metals, we have found 3 cases of sensitization to beryllium. Of
      these 3 cases, we regard the first 2 as having relevant sensitization. Beryllium
      chloride (1% pet.) was positive in 3 patients and negative in 150 controls.

PMID- 1395590
TI  - A glove with exceptional protective features minimizes the risks of working with
      hazardous chemicals.
AB  - In continuation of our preceding studies, we disclose long-term experiments to
      test more extensively the protective power of the novel 4H Glove. 2 compounds
      encountered in modern electron microscopy technique, 1-hexadecene (1-HD) and 2
      hydroxyethyl acrylate (2-HEA), which elicit allergic and/or toxic reactions in
      laboratory workers, were tested for their penetration through the 4H Glove
      material 1-HD has not to our knowledge been tested on any glove material. 2-HEA
      was known to have a breakthrough time exceeding 240 min; in contrast, it
      penetrates the common latex or vinyl gloves within minutes. When exposing the
      outside of a 4H Glove to 2-HEA for 200 h at 21 degrees C and then attaching the
      reverse unexposed side to a sensitized volunteer's forearm, 30 min of contact
      elicited a barely visible reddening of the skin at the contact site which
      disappeared within 24 h; 90 min of contact caused a somewhat stronger reddening
      limited to the contact area, which disappeared within 2 days. By the same
      criteria, 1-HD did not penetrate through the 4H Glove in 200 h. In an additional
      experiment, breakthrough time of 1-HD on latex gloves was less than 30 min.

PMID- 1395591
TI  - Vaccination granulomas and aluminium allergy: course and prognostic factors.
AB  - 21 children who had cutaneous granulomas following immunization with a vaccine
      containing aluminium hydroxide, and who had positive patch tests to aqueous
      aluminium chloride and/or to a Finn Chamber, were followed for 1 to 8 years.
      During the period of observation, the symptoms cleared in 5 children, improved in
      11, and remained unchanged in 5. The course of the granulomas could not be
      correlated with sex or atopy, nor with intensity of the initial aluminium patch
      test. 4 children were patch tested again with aluminium.

PMID- 1395592
TI  - A multicentre study of contact sensitization in children. Gruppo Italiano Ricerca
      Dermatiti da Contatto e Ambientali (GIRDCA).
AB  - The results of 7 months of patch testing with a standard series of 26 allergens
      in 323 children with eczematous conditions or itching palmoplantar psoriasis
      under the age of 14 years are reported. 114 (35.3%) of the children had 1 or more
      positive reactions to this standard series. 28 children (8.7%) were
      polysensitive. On the basis of personal history, additional series of allergens
      and/or specific allergens were also tested. 61.7% (90/146) of positive reactions
      were considered relevant to the current dermatitis. Metals, medicaments,
      preservatives or fragrances, and shoe components were the major sources of
      contact sensitization. It is suggested that patch testing be done more frequently
      in evaluating dermatitis in children.

PMID- 1395593
TI  - Tinuvin P in a spandex tape as a cause of clothing dermatitis.
AB  - We report a 54-year-old female with allergic contact dermatitis from 2-(2-hydroxy
      5-methylphenyl)benzotriazole (Tinuvin P) in a spandex tape sewn into underwear.
      Tinuvin P is used as an ultraviolet light absorber for stabilizing plastics and
      the other organic materials against discoloration and deterioration. It is
      effective in protecting synthetic and natural fibers, polyesters, chlorinated
      polyesters, polystyrene, polyvinyls, cellulose acetate, ethyl cellulose,
      acrylates, dyes, waxes, detergents, cosmetic formulations, etc. Our patient
      developed itchy erythema on her shoulders, chest and upper back after wearing
      underwear for 1 night. She showed positive reactions to spandex tape sewn into
      the underwear. She also reacted to 2-(2-hydroxy-5-methylphenyl)benzotriazole
      (Tinuvin P), which was contained in the spandex. No cross-reaction to other
      benzotriazoles was seen.

PMID- 1395594
TI  - Allergic contact dermatitis from chironomids.
AB  - Although Type I allergy to chironomids is well-known, allergic contact dermatitis
      caused by these cosmopolitan insects has not previously been reported. In the
      case we describe in this report, patch tests disclosed a delayed-type
      hypersensitivity to 4 different species of chironomids (larvae of Chironomus
      thummi, Chironomus plumosus, and 2 different species of Glyptotendipes) as the
      probable cause of airborne facial contact dermatitis. An additional asymptomatic
      immediate-type allergy to chironomids was demonstrated by scratch tests and
      specific IgE. The possible sources of exposure to chironomids, their allergens
      and their distribution are discussed with regard to clinical implications.

PMID- 1395595
TI  - Changing trends in the epidemiology of contact dermatitis in Singapore.
AB  - All patients seen in the Contact Dermatitis Clinic of the National Skin Centre,
      Singapore (and the former Middle Road Hospital) between January 1986 and December
      1990 were analysed retrospectively. 5557 patients comprising 2634 (47.4%) males
      and 2923 (52.6%) females were patch tested. 3154 (56.8%) patients had 1 or more
      positive reactions. The majority of the patients were Chinese (78.0%), followed
      by Malays (11.5%), Indians (8.1%) and other minority races (2.4%). The majority
      of positive reactions belonged to the 21-40 age group. The incidence of
      positivity decreased after 60 years. The commonest allergens responsible were
      nickel (17.7%), fragrance (13.3%), neomycin (6.9%), colophony (6.6%) and
      proflavine (6.5%). Both neomycin and proflavine were commonly used as over-the
      counter medicaments. Compared to an earlier report in 1988, there were
      differences in the incidence of contact sensitivity to some allergens. Potassium
      dichromate, which used to be a common allergen, was less common. Some allergens
      (carba-mix, naphthyl-mix, caine-mix and PCMX) have been removed from our standard
      series as they were uncommon causes of contact allergy. Thimerosal and Amerchol L
      101 were added in their place.

PMID- 1395596
TI  - Patch testing with pure palladium metal in patients with sensitivity to palladium
      chloride.
AB  - During a 15-month period, 536 patients being investigated for suspected contact
      dermatitis were patch tested with the European standard series and palladium
      chloride 1% pet. 13 patients (2.4%) had a positive allergic response to palladium
      chloride and all 13 were also allergic to nickel. 12 of these 13 patients
      consented to further patch testing with discs of pure palladium metal foil, and
      none reacted. We have shown previously that palladium chloride patch test
      material contains traces of nickel, and propose an explanation for these results
      in terms of the additive effect of allergens when tested in combination.

PMID- 1395598
TI  - A prospective study of the development of hand eczema in an automobile
      manufacturing industry.
AB  - We have not been able to find any prospective study of the risk of developing
      occupational dermatitis in the car manufacturing industry. To try to define
      individual predictive risk factors for the development of hand eczema and to
      determine the prevalence of hand eczema within 1 year in an automobile
      manufacturing industry, we investigated prospectively 1564 new employees during
      one year of employment. Only persons with previous atopic dermatitis or hand
      eczema were restricted to dry and clean workplaces. The employees were personally
      interviewed and examined before their employment. Written questionnaires were
      used at 3 and 12 months to obtain information on type of work, exposure,
      protection and hand dermatitis. All patients developing hand eczema were
      examined, patch tested and followed to determine the course and consequence of
      their eczema. The risk turned out to be only 4% on average, but significantly
      higher in females (6%). Certain sections within the factory such as wet work
      (canteen/kitchen and cleaning) and work in the paint shop with high exposure to
      organic solvents carried significantly higher risks. Heavy exposure to mineral
      oil, a known risk factor, was effectively counteracted by the extensive use of
      protective gloves to yield a lower than average prevalence in the press and body
      shop. Individual risk factors for the development of hand eczema were previous
      hand eczema, atopic dermatitis, but also wool intolerance and hay fever as
      isolated phenomena. Most cases of hand eczema were mild, of irritant contact type
      and only 1 employee developed an allergic contact dermatitis due to the working
      environment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1395597
TI  - Air oxidation of d-limonene (the citrus solvent) creates potent allergens.
AB  - Products containing as much as 95% of d-limonene are used for, e.g., degreasing
      metal before industrial painting and for cleaning assemblies. Experimental
      studies on the sensitizing potential of limonene show diverging results. In a
      previous study, we found that the sensitizing potential of d-limonene increased
      with prolonged air exposure. The aim of this study was to make further chemical
      analyses, to identify compounds formed by air exposure of d-limonene and to study
      their allergenic potential. d-limonene was found to be a sensitizer after
      prolonged exposure to air according to 2 Freund's complete adjuvant test (FCAT)
      experiments and 1 guinea pig maximization test (GPMT) study. No significant
      response was obtained to d-limonene not air exposed, even if the animals were
      sensitized to oxidized d-limonene. 5 main oxidation products of d-limonene were
      identified. (R)-(-)-carvone and a mixture of cis and trans isomers of (+)
      limonene oxide were found to be potent sensitizers, while no significant
      reactions were obtained in the animals induced with a mixture of cis and trans
      isomers of (-)-carveol. It can be concluded that air oxidation of d-limonene is
      essential for its sensitizing potential, and that potent allergens are created.

PMID- 1395599
TI  - Some observations on mango and mokihana dermatitis from Hawaii.

PMID- 1395600
TI  - Patch testing with clobazam: relapse of generalized drug eruption.

PMID- 1395601
TI  - Sensitization risk of pyrethroid insecticides.

PMID- 1395602
TI  - Hypersensitivity to semisynthetic penicillins and cross-reactivity with
      penicillin.

PMID- 1395603
TI  - Contact dermatitis and cross-sensitivity from sulconazole nitrate.

PMID- 1395604
TI  - Patch test reactivity to the PPD-black-rubber-mix (industrial rubber chemicals)
      and individual ingredients.

PMID- 1395605
TI  - Contact sensitivity to pyrazinobutazone (Carudol) with positive oral provocation
      test.

PMID- 1395606
TI  - Photosensitivity from harvesting lovage (Levisticum officinale).

PMID- 1395607
TI  - Delayed allergy to diclofenac.

PMID- 1395608
TI  - Hardening.

PMID- 1395609
TI  - Allergic contact dermatitis from the preservative 1,2-benzisothiazolin-3-one (1,2
      BIT; Proxel): a case report, its prevalence in those occupationally at risk and
      in the general dermatological population, and its relationship to allergy to its
      analogue Kathon CG.
AB  - Occupational contact allergy to 1,2-benzisothiazolin-3-one (1,2-BIT, Proxel) is
      analysed. This compound is widely used in industry as a preservative in water
      based solutions such as pastes, paints and cutting oils. The optimal
      concentration for patch testing proved to be 0.4 g/l (0.04%) in water. In 4 out
      of 17 patients (23%) at occupational risk (painters, paper-hangers), contact
      allergy to 1,2-BIT was found. Of 556 consecutive dermatological patients without
      clear occupational risk, 10 (1.8%) showed positive patch tests to 1,2-BIT; in 3
      patients 1,2-BIT contact allergy was related to domestic paper-hanging. Although
      the chemical structure of 1,2-BIT shows some analogy with the preservative Kathon
      CG, true cross-sensitivity was found to be unlikely.

PMID- 1395610
TI  - Systemic contact dermatitis due to mercury.

PMID- 1395611
TI  - Patch testing with a dilution series of nickel sulfate.

PMID- 1395612
TI  - Baseline transepidermal water loss in 3 different anatomical regions in healthy
      and eczematous subjects.

PMID- 1395613
TI  - Contact allergy to dibromodicyanobutane in a cosmetic cream.

PMID- 1395614
TI  - Contact dermatitis from avoparcin.

PMID- 1395615
TI  - Allergic contact dermatitis from nickel in an eye pencil.

PMID- 1395616
TI  - Erythema-multiforme-like contact dermatitis from dimethoate.

PMID- 1395617
TI  - Contact allergy to cane reed in a clarinettist.

PMID- 1395618
TI  - Does patch testing with ammoniated mercury in a Finn Chamber give a false
      positive reaction?

PMID- 1395619
TI  - Contact dermatitis from tioconazole.

PMID- 1395620
TI  - Erythroderma following the intradermal injection of the corticosteroid
      budesonide.

PMID- 1395621
TI  - Systemic contact dermatitis due to amlexanox.

PMID- 1395622
TI  - Contact urticaria and severe anaphylaxis from rifamycin SV.

PMID- 1395623
TI  - Patch testing with pollens of Gramineae in patients with atopic dermatitis and
      mucosal atopy.

PMID- 1395624
TI  - Hearing aid depigmentation.

PMID- 1395625
TI  - Occupational allergic contact dermatitis from caffeates in poplar bud resin in a
      tree surgeon.

PMID- 1395626
TI  - Contact sensitivity to tioconazole and other imidazoles.

PMID- 1395627
TI  - Kaposi-like acro-angiodermatitis of amputation stump caused by suction socket
      prosthesis.

PMID- 1395628
TI  - Multicentre studies and conflicting prevalence data.

PMID- 1395629
TI  - The substitution of talcum powder in rubber gloves for patients allergic to corn
      starch not advisable.

PMID- 1395630
TI  - Shiitake (Lentinus edodes) dermatitis.
AB  - Shiitake (Lentinus edodes) is a mushroom which is eaten in Chinese and Japanese
      meals and is nowadays the second most commonly produced edible mushroom in the
      world. Shiitake dermatitis was first described by Nakamura in 1977. This disease
      presents with very characteristic skin manifestations. From April 1974 to April
      1991, I have observed 51 patients with shiitake dermatitis. The following
      description reviews the clinical manifestations, laboratory investigations and
      sources of shiitake dermatitis.

PMID- 1395631
TI  - Contact dermatitis from metallic palladium in patients reacting to palladium
      chloride.
AB  - 1307 consecutive patients were patch tested with PdCl2 1% pet. 32 patients were
      positive; 29 also showed a reaction to NiSO4. 470 patients were additionally
      tested with a metallic palladium disc. 3 had a positive reaction, and none of
      them reacted to PdCl2 or NiSO4 pet. A positive patch test to PdCl2 pet. is in
      most cases probably due to a cross-reaction with nickel in nickel-sensitive
      subjects. Patients positive to PdCl2 tolerate skin contact with metallic
      palladium.

PMID- 1395632
TI  - Propyl gallate on liposomes.
AB  - A hypothesis suggesting that the allergic potential of propyl gallate is boosted
      by its attachment to liposomes in cosmetics is put forward. 13 women with allergy
      to propyl gallate are presented.

PMID- 1395633
TI  - Final diagnoses in patients referred for patch testing.
AB  - The final diagnoses made in 989 patients consecutively patch tested in 1990 have
      been reviewed. Among the men, their dermatitis was entirely occupational in 17.9%
      and partially so in 12.5%. Among the women, it was entirely occupational in 6.4%
      and partially so in 9.5%. In both groups, irritants exceeded allergens as the
      cause, whereas allergens superseded irritants in the patients with a non
      occupational eczema caused or aggravated by external factors. It seems likely
      that domestic irritants were overlooked in patients with a non-occupational
      dermatitis.

PMID- 1395634
TI  - Comparative study of TRUE Test and Finn Chamber patch test techniques in
      Singapore.
AB  - This is a report on a comparative study of the reactivity of TRUE Test and Finn
      Chamber patch test techniques. 413 patients attending a contact dermatitis clinic
      in Singapore were simultaneously patch tested with panels 1 and 2 of the TRUE
      Test standard series and with corresponding allergens (Hermal, Hamburg) using
      Finn Chambers. The left/right application of the TRUE Test and Finn Chambers was
      randomized. The concordance of positive patch test reactions to the 2 test
      techniques was studied. The number of patient with positive reactions was 38% and
      42% for TRUE Test and Finn Chamber techniques, respectively (n.s.). The overall
      concordance of positive patch test reactions was 64% (209/328). 13% (42/328) of
      positive reactions appeared on TRUE Test only and 24% (77/328) on Finn Chamber
      only. When only relevant positive reactions were considered, the concordance rate
      was 67%; 11.6% of positive reactions appeared on TRUE Test only and 21% on Finn
      Chamber only. Positive reactions to p-phenylenediamine (PPD) and neomycin were
      more frequent with the Finn Chamber technique than with TRUE Test, i.e., false
      negative reactions to PPD and neomycin were more likely to occur with TRUE Test.
      It appeared that the TRUE Test and Finn Chamber techniques were comparable when
      used for patch testing. However false negative and false positive patch test
      reactions can occur when using either technique.

PMID- 1395635
TI  - Further investigation of the prohapten concept: reactions to benzene derivatives
      in man.
AB  - p-Phenylenediamine (PPDA) is a strong contact sensitizer which is included in the
      standard patch test tray and which can also act as an indicator of allergy to
      related substances by virtue of cross-reactions. In a previous study, the pattern
      of cross-reactions between PPDA and related substances was investigated in the
      guinea pig to evaluate the prohapten concept. The results provided some support
      for this concept, but also indicated that a number of reactive intermediates
      might be behaving as haptens. This work has now been extended to an examination
      of the prohapten concept in man in PPDA-allergic subjects. These subjects were
      tested with 7 substituted benzenes, plus PPDA. Of these, the 1,4-substituted
      benzenes hydroquinone, Metol, PPDA and p-aminophenol are all capable
      theoretically of giving rise to benzoquinone by oxidation (after demethylation in
      the case of Metol). However, as had been the case in the guinea pig, only a
      limited degree of cross-reaction was observed. Only one of the subjects allergic
      to PPDA gave a clearly positive allergic reaction to benzoquinone. The data
      provided only limited support for the prohapten concept in terms of benzoquinone
      as the ultimate hapten for a range of 1,4-substituted benzenes. As indicated in
      the guinea pig, a range of reaction intermediates or indeed other oxidation
      products may be involved. So, for each molecule, the sensitizing activity and
      potential to give rise to cross-reactions may depend on the balance between
      routes of skin metabolism.

PMID- 1395636
TI  - Possible origin of the skin sensitization potential of isoeugenol and related
      compounds. (I). Preliminary studies of potential reaction mechanisms.
AB  - Although many simple chemicals can give rise to the phenomenon of allergic
      contact dermatitis, it is rare that the mechanism of reaction between the
      chemical hapten and skin protein is known. A further complication is that
      metabolic processes may produce substantial changes to a chemical penetrating
      skin. Thus the skin contactant may be regarded as a prohapten which will give
      rise to the true hapten in vivo. In this study, the possible reaction mechanisms
      for a number of related simple aromatic chemicals have been investigated. The
      approach taken was to evaluate potential reaction mechanisms by assessing the
      degree to which chemicals could cross-react in sensitization tests. By careful
      choice of chemicals, it was then possible to confirm (or reject) options. Using
      this approach, a number of reaction schemes were investigated for eugenol,
      isoeugenol, dihydroeugenol, anethole and several related chemicals. The patterns
      of sensitization obtained and the cross-reactions observed indicated clearly that
      electrophile/nucleophile interactions were unlikely to provide a complete
      explanation of the sensitization processes. Eugenol and isoeugenol are not
      mutually cross-reactive, yet both cross-reacted with dihydroeugenol. Examination
      of the possible reaction mechanisms allows the speculation that eugenol reacts in
      part via a phenolic radical mechanism, whilst isoeugenol reacts largely via
      formation of an orthoquinone. Both reaction mechanisms are proposed for
      dihydroeugenol.

PMID- 1395637
TI  - Recency, primacy, and memory: reappraising and standardising the serial position
      curve.
AB  - In this paper we consider the serial position curve in immediate verbal free
      recall. A large literature has argued that two components of the serial position
      curve, recency and primacy, reflect the functioning respectively of short-term
      and of long-term memory. However, there are a number of difficulties in
      interpreting the recency effect as a phenomenon uniquely associated with short
      term memory. Moreover, the serial position curve has been used widely for
      clinical investigations in patients with memory deficits. This is despite the
      lack of norms for the measures derived from the curve. We present a set of
      standardised norms based on 321 Italian normal subjects. These norms are shown to
      be applicable both to an English speaking population, and to three groups of
      brain damaged-patients, namely Alzheimer's, amnesics, and frontals. The
      standardised norms offer a clinical and experimental tool which, coupled with a
      multiple single case approach, allows us to show dissociations and double
      dissociations among the performance patterns obtained from all three pathological
      groups. The paper concludes with a discussion of a possible interpretation of the
      recency effect as a emergent property of all types of memory system, including
      verbal short-term memory. Taking into account previous literature as well as our
      own data, the recency effect in immediate verbal free recall is here interpreted
      in terms of a two-component view of verbal short-term memory.

PMID- 1395638
TI  - Foot and eye preferences in adults: relationship with handedness, sex and age.
AB  - Age, sex, and handedness effects in foot and eye preferences were studied by
      questionnaire in large samples of normal adult populations from five different
      countries (total sample, n = 5064). Foot and eye preference were significantly
      associated with handedness category (right or left) in all the 10 sex by country
      samples for foot, and in 9/10 samples for eye. The overall frequencies of crossed
      preferences were 5% between hand and foot and 19.5% between hand and eye. In
      right-handers, a gradual shift toward the "right" with increasing age was
      systematically observed, both for footedness and eyedness. The proportion of
      crossed hand-foot preference was higher in men than women (7.4% vs 2.5%), and
      higher in left-handers than right-handers (16.3% vs 4.1%). Sex differences in the
      proportion of crossed hand-eye preference were variable from one country to the
      other.

PMID- 1395639
TI  - Darkness improves line bisection in unilateral spatial neglect.
AB  - This study was performed to determine the influence of background illumination on
      the performance of patients with left visual neglect. We examined six RBD
      patients with unilateral visual neglect, and as controls six RBD patients and six
      LBD patients without neglect. A luminous line consisting of LEDs was used in a
      line bisection task under two conditions, normal illumination and darkness. As
      expected, neglect patients made large rightward errors under normal illumination.
      Their performance improved by about 43% in darkness. Our results are discussed
      with reference to earlier studies of space exploration without visual guidance.

PMID- 1395640
TI  - The performance of postencephalitic amnesic subjects on two behavioural tests of
      memory: concurrent discrimination learning and delayed matching-to-sample.
AB  - The performance of a group of three postencephalitic subjects with anterograde
      amnesia was examined on a series of concurrent visual discrimination problems and
      on a test of visual recognition, delayed matching-to-sample. These tests were
      chosen as they have been used to assess experimental models of anterograde
      amnesia in nonhuman primates. In comparison with a group of normal subjects the
      postencephalitic group were impaired on the more difficult concurrent
      discrimination problems. They also performed poorly on the matching-to-sample
      task when given lists of items to remember or given increased retention
      intervals. The pattern of performance of the postencephalitic group matched
      closely that of a group of Korsakoff subjects, indicating that these behavioural
      tests are equally sensitive to different types of anterograde amnesia.

PMID- 1395641
TI  - Handedness in childhood autism shows a dissociation of skill and preference.
AB  - Hand preference and hand skill were assessed in 20 children with autism, 20
      normal controls and 12 children with mental retardation. 90% of the normal
      controls and 92% of the children with mental retardation showed concordance for
      hand preference and hand skill (i.e. the preferred hand was also the more
      skillful), whereas only 50% of the children with autism showed concordance of
      preference and skill, the remaining 50% preferring to use the hand which was less
      skillful. Children with autism also showed a lesser degree of handedness and a
      lesser degree of consistency than the other groups, although this was unrelated
      to the discordance of skill and asymmetry. A developmental model of handedness is
      proposed in which the development of handedness as preference is ontogenetically
      prior to the development of handedness as skill asymmetry, such that in normal
      children the development of skill asymmetry occurs as a secondary consequence of
      the establishment of preference. The causal sequence is disrupted in autism, so
      that although preference is established, it does not subsequently result in
      concordant skill asymmetry.

PMID- 1395642
TI  - Auditory and visual verbal short-term memory in aphasia.
AB  - Phonological short-term memory was investigated in 24 aphasic left brain-damaged
      patients and in 12 matched controls. Aphasic patients have a reduced auditory and
      visual immediate memory span and show the standard detrimental effect of
      phonological similarity on immediate retention only when the stimuli are
      auditorily presented, while in the control group the effect is present with both
      auditory and visual input. Most patients have phonological processing deficits,
      but two patients have an impaired immediate verbal memory in the absence of
      analysis disorders. These results, in line with most individual case studies of
      patients with selective deficits of verbal short-term memory, are interpreted
      with reference to a model distinguishing a phonological short-term store
      component of memory, to which auditory input has direct and automatic access, and
      a rehearsal component, that, after phonological recoding, conveys visually
      presented stimuli to the phonological store. This latter system, that appears to
      become fully operational later in development, is less resistive to brain damage.

PMID- 1395643
TI  - Do "right-armed" lefthanders have different lateralization of motor control for
      the proximal and distal musculature?
AB  - Geschwind and Galaburda (1985) have suggested that specialization for the control
      of distal and proximal musculature might be located in different hemispheres in
      some individuals. Because inconsistent lefthanders (as defined by Ponton, 1987;
      Peters and Servos, 1989) tend to write with the left hand but throw with the
      right arm, and have a stronger right arm (Peters, 1990), it was thought that
      individuals in this group might provide evidence for the prediction made by
      Geschwind and Galaburda. This did not prove to be the case for tapping speed,
      where righthanders, inconsistent and consistent lefthanders all showed
      congruence. It appears that the question "are some left-handers right-armed?" can
      be answered only relative to specific activities.

PMID- 1395644
TI  - Simple reaction time to lateralized visual stimuli is not related to the
      hemispheric side of lesion.
AB  - The effect of a single brain lesion on Reaction Times (RTs) to unpatterned visual
      stimuli was studied in 20 right brain-damaged (RBD) and 19 left brain-damaged
      (LBD) patients with single small vascular lesions confined to one hemisphere and
      free of visual field defects and of significant neuropsychological abnormalities
      (e.g. aphasia or hemineglect). The stimulus was presented in the field either
      ipsilateral or contralateral to the brain lesion. The stimulus location was
      either blocked in each hemifield or randomly alternating between fields. RTs in
      RBD patients were not statistically different from RTs in LBD patients.
      Intrahemispheric site of the lesion also was irrelevant for the lengthening in
      RTs. Responses to blocked presentations were faster than to random presentations.
      Responses to the hemifield contralateral to the brain lesion were slower than to
      ipsilateral hemifield, and the difference was unrelated to the absolute values of
      RTs. It is concluded, in contrast to other reports, but in agreement with the
      more recent literature, that there is no hemispheric dominance for RTs.

PMID- 1395645
TI  - The septo-hippocampal pathways and their relevance to human memory: a case
      report.
AB  - The interaction between the septal region and the hippocampal formation appears
      indispensable for the maintenance of normal memory and learning mechanisms in
      humans. The disruption of some combination of septo-hippocampal pathways,
      especially the disruption of the "dorsal route", deteriorates explicit memory
      functions. The case of a 25-year-old male patient is presented who developed
      anterograde and to a certain extent retrograde amnesia following rupture and
      repair of an arteriovenous malformation in the atrium of the left ventricle. A
      left-sided lesion of the dorsal route involving the posterior cingulate bundle,
      the longitudinal striae (as part of the supracommissural hippocampus) and the
      fornix appeared responsible for his mnemonic deficits. The implications of these
      findings for the understanding of other clinical cases, particularly those with
      lesions of the septal region, the anterior and posterior singular gyrus/cingulate
      bundle and the fornix are discussed.

PMID- 1395646
TI  - Brain correlates of hand dominance: the association between peripheral and
      cerebral asymmetries revisited.
AB  - Measures reflecting central processing of somatosensory stimulation were recorded
      in left- and in right-handed subjects in order to evaluate differences between
      the two handedness groups in the vertical, rather than lateral, axis of
      processing. Somatosensory evoked potentials were recorded in left- and right
      handers following electrical stimulation of the median nerve at the wrist. The
      relative vertical balance of processing was probed by comparing the amplitudes of
      the underlying activity in early evoked potentials, presumably originating
      subcortically, with later, cortically originating potentials. Central conduction
      time (CCT) of the sensory volleys was also recorded. The data revealed higher
      amplitude ratios (ARs) between subcortical and cortical potentials, as well as
      shorter CCTs, in left-handers. These results demonstrate that transmission
      differences between the handedness groups may occur early in central nervous
      system (CNS) conductance. The results are further discussed in light of evidence
      suggesting that stronger reliance on a subcortical mode of processing may
      underlie phenomenon of left-handedness.

PMID- 1395647
TI  - Subjective mood state and perception of emotion in chimeric faces.
AB  - Levy, Heller, Banich, and Burton (1983) have shown that hemispheric activational,
      or arousal, style, as measured by direction and consistency of choice of the
      "happer face" on a free-viewing Chimeric Faces Test, is highly reliable and
      varies across individuals who otherwise presumably have similar cortical
      organization (e.g., right-handed college students). The current experiment asks
      whether such individual differences in hemispheric arousal style are moderated by
      long-term, in the sense of enduring, individual differences in mood, as measured
      by the Profile of Mood States (POMS) questionnaire. Like Levy et al.'s subjects,
      most of our subjects (126 right-handed college students) made most of their
      choices on the Chimeric Faces Test based on the emotional cue (the smile)
      positioned in the half of the face to the viewer's left, or left visual hemifield
      (LVH), whereas a small minority were equally consistent in making their choice
      based on the emotional cue positioned in the half of the face to the viewer's
      right, or right visual hemifield (RVH). Performance on the Chimeric Faces Test,
      however, proved to be unrelated to scores on the POMS questionnaire. This
      suggests that hemispheric arousal style, as indexed by the Chimeric Faces Test,
      is robust enough, for a population of normal right-handers, to transcend any
      differences in mood as measured by the POMS questionnaire.

PMID- 1395648
TI  - The effects of parental immunoreactivity on pregnancy, birth, and cognitive
      development: maternal immune attack on the fetus?
AB  - The effects of parental immunoreactivity were tested in two ways on questionnaire
      data collected from 468 children and their families. (1) It was found that the
      presence of learning difficulties in boys was associated with pregnancy and birth
      complications, as well as with maternal immunoreactivity. Paternal
      immunoreactivity did not appear to be related to any of the variables in
      question. (2) The antecedent brother effect, that children, particularly males,
      with older brothers have higher rates of the same set of variables, was not
      found. Maternal immunoreactivity emerges as a risk factor for pregnancy, birth,
      and cognitive development, but not exclusively by the proposed mechanism of
      maternal immune attack on the fetus.

PMID- 1395649
TI  - Associations between hand and foot preference in 3- to 5-year-olds.
AB  - Associations between foot and hand preference behavior were examined in 3-, 4-,
      and 5-year-olds. Analysis of the general trichotomous (right, left, mixed)
      distribution of preferences indicated no sex or age group differences, while
      noting that 39% were mixed-footed compared to 17% not favoring one hand over the
      other. Frequency of paired (congruent and cross-lateral) preferences revealed
      that two patterns, Right-hand/Right-foot (52%) and Right-hand/Mixed-foot (23%)
      accounted for the vast majority (75%) of subjects. Of the total number of right
      handers, most (67%) preferred the right foot, while only 19% of the left-handers
      were congruent. Thus, supporting findings reported on older populations that
      right-handers are more consistently right-footed, than left-handers are left
      footed. Behavior of the mixed- and right-handed sample was similar, suggesting an
      overall predominance of these lateral characteristics in young children.

PMID- 1395650
TI  - Multiple phantom limbs in a child.
AB  - This case report describes multiple phantom feet in a child after amputation of a
      leg. The subject is a 16-year-old girl who was born with a right leg 10 cm
      shorter than the left and who at the age of 6 was amputated below the right knee
      so that she could wear a prosthesis that would give her normal mobility. The girl
      reports that she subsequently experienced 2 phantom feet and 3 sets of phantom
      toes which have persisted to the present time. Each phantom has a distinct size,
      length and position in relation to the others and each is also the site of vivid
      sensations such as heat, tickle, and fatigue as well as voluntary and involuntary
      movement. She also describes sensations that resemble sensations experienced
      before the amputation: one of her phantom feet feels flat and locked into a
      forward position which corresponds with the actual shape and position of her
      congenitally deformed amputated foot. The implications of multiple phantoms are
      discussed with reference to recent concepts of phantom limbs.

PMID- 1395651
TI  - Consistency in recalling features of former head injuries: retrospective
      questionnaire vs. interview retest.
AB  - The probability and features of memory concerning former head injuries with loss
      of consciousness was assessed in two formats: a group-test questionnaire and a
      retest using personal individual interview. Results are given concerning the
      greater likelihood of reporting short 'permanent' retrograde amnesias in the
      interview.

PMID- 1395652
TI  - The dynamic performance model of skeletal muscle.
AB  - Applications of electrical stimulation to the nerve or muscles associated with a
      defunct limb joint due to stroke or spinal cord injury are a viable means of
      restoring a certain level of functional movement to the patient. In this article,
      the currently acceptable physiology of motor control is outlined and used as a
      criterion for electrophysiological and biomechanical performance evaluation of
      contemporary electrical stimulation strategies used by various systems attempting
      to duplicate such motor control in an effort to restore meaningful limb function.
      Strategies associated with surface, nerve, intramuscular, and reflex stimulation
      are critically reviewed with special reference to voluntary sensory motor control
      of a limb joint rather than an isolated muscle.

PMID- 1395653
TI  - Biofluid dynamics at arterial bifurcations.
AB  - Hemodynamics has long been suspected of being involved in arterial diseases,
      e.g., atherosclerosis. Seemingly good correlation between the atherosclerosis
      localization and the flow disturbance around bends and bifurcations in large
      arteries has prompted many studies of blood flow around those regions. This
      article reviews and critiques biofluid studies at various arterial bifurcations.
      Both experimental and theoretical models vary greatly in the major assumptions
      and parameters. The issues discussed include: possible errors from two
      dimensional models, the validity of steady flow studies, the existence and
      influence of the secondary flow, effects of non-Newtonian blood rheology,
      influences from arterial wall distensibility, effects of the Reynolds number,
      effects of the area ratio, effects of the Womersley number, effects of corner
      curvatures, effects of bifurcation angle, errors in the measurement and
      calculation of wall shear rate, and the possible existence of turbulence.

PMID- 1395654
TI  - Nutrition in critically ill patients--the location of nutrient delivery.

PMID- 1395655
TI  - Prognostic factors in sepsis: the cold facts.

PMID- 1395656
TI  - An R.S.V.P. to R.S.V. (respiratory syncytial virus): declining mortality rates.

PMID- 1395657
TI  - Nutritional outcome and pneumonia in critical care patients randomized to gastric
      versus jejunal tube feedings. The Critical Care Research Team.
AB  - OBJECTIVE: To compare nutritional status, gastric colonization, and rates of
      nosocomial pneumonia in ICU patients randomized to gastric tube feeding vs.
      patients fed by an endoscopically placed jejunal tube. DESIGN: Randomized,
      prospective study. SETTING: Medical and surgical ICUs at Boston City Hospital;
      surgical ICU at University Hospital. PATIENTS: Of the 38 study patients, 19 were
      randomized to gastric tube feeding and 19 were randomized to an endoscopically
      placed jejunal tube. The two groups were similar in age, sex, race, underlying
      disease, and type of surgery. RESULTS: The two patient groups were similar in
      number of days fed, duration of ICU stay, duration of mechanical ventilation,
      days of antibiotic therapy, and days with fever. Compared with the gastric group,
      the jejunal group had more patients with circulatory shock on admission (79% vs.
      68.4%), higher admission Acute Physiology Score (24.0 vs. 21.7), and fewer
      patients with pneumonia at randomization (26.3% vs. 31.6%). The jejunal group
      received a significantly higher percentage of their daily goal caloric intake (p
      = .05), and had greater increases in serum prealbumin concentrations (p < .05)
      than the patients with gastric tube feeding. Although the jejunal tube group had
      more days of diarrhea (3.3 +/- 6.6 vs. 1.8 +/- 2.9), this difference was not
      statistically significant. Nosocomial pneumonia was diagnosed clinically in two
      (10.5%) patients in the gastric tube group and in no patients in the jejunal tube
      group. CONCLUSIONS: Patients fed by jejunal tube received a significantly higher
      proportion of their daily goal caloric intake, had a significantly greater
      increase in serum prealbumin concentrations, and had a lower rate of pneumonia
      than patients fed by continuous gastric tube feeding.

PMID- 1395658
TI  - Effect of acidified enteral feedings on gastric colonization in the critically
      ill patient.
AB  - OBJECTIVE: To evaluate the effect of acidified enteral nutritional formulas
      (feedings) on gastric colonization and pH in critically ill patients. DESIGN:
      Randomized, double-blind trial of three groups: a) regular feedings into the
      stomach; b) regular feedings into the duodenum; and c) acidified feedings into
      the stomach. Nasogastric aspirates for gastric pH and microbiological
      determinations were obtained daily for a mean of 5 days after feeding began.
      SETTING: ICU at a tertiary care hospital. PATIENTS: Thirty-one patients indicated
      to receive enteral feedings before day 4 in the ICU were randomized. Seven
      patients had their feedings discontinued because of intolerance, accidental
      extubation, or tolerance of oral supplementation. One patient received the wrong
      feedings and was dropped from the study. A total of 23 patients finished the
      study. They were mostly trauma (n = 15) or neurosurgical (n = 6) patients. The
      average age was 40 yrs (range 15 to 71). INTERVENTIONS: An enteral formula with a
      pH of 6.5 was used as the control feeding. Hydrochloric acid was added to the
      control feeding to titrate the pH to 3.5 and this acidified enteral formula was
      given to the experimental group. All patients received continuous enteral
      feedings via an 8-Fr feeding tube. MAIN RESULTS: Seven of eight patients
      receiving the acidified feedings were sterile (no microbial growth) on receiving
      feedings compared with five of 15 of those patients receiving regular feedings (p
      = .027). For those patients initially colonized, four of four patients receiving
      acidified feedings immediately became sterile and remained so. Only two of ten
      patients receiving regular feedings remained sterile (p = .021). The mean gastric
      pH of the acidified group was 3.2 compared with the group receiving regular
      feedings into the stomach (pH = 4.7) and the group receiving regular feedings
      into the duodenum (pH = 3.8) (p < .01). There was no evidence of gastrointestinal
      bleeding in any patient. CONCLUSIONS: Acidified enteral feedings are effective in
      eliminating and preventing gastric colonization in critically ill patients.
      Further investigation is needed to assess its effect on nosocomial infection
      rates.

PMID- 1395659
TI  - Hypothermia in the sepsis syndrome and clinical outcome. The Methylprednisolone
      Severe Sepsis Study Group.
AB  - OBJECTIVE: To evaluate the consequences of clinical hypothermia associated with
      sepsis syndrome and septic shock. DESIGN: Analysis of data from a multi
      institutional, randomized, placebo-controlled, prospective study with
      predetermined end-point analysis of development of shock, recovery from shock,
      hospital length of stay, and death. SETTING: Multi-institutional medical and
      surgical ICUs. PATIENTS: Patients meeting predetermined criteria for severe
      sepsis syndrome. INTERVENTIONS: Appropriate sepsis and shock care with 50% of
      patients receiving methylprednisolone and 50% receiving placebo. MEASUREMENTS AND
      MAIN RESULTS: The occurrence rate of hypothermia (< 35.5 degrees C) is 9% in this
      population. When compared with febrile patients, hypothermic patients had a
      higher frequency of central nervous system dysfunction (88% vs. 60%), increased
      serum bilirubin concentration (35% vs. 15%), prolonged prothrombin times (50% vs.
      23%), shock (94% vs. 61%), failure to recover from shock (66% vs. 26%), and death
      (62% vs. 26%). The hypothermic patients were also more likely to be classified as
      having a rapidly or ultimately fatal disease upon study admission. CONCLUSIONS:
      This prospective study confirms that hypothermia associated with sepsis syndrome
      has a significant relationship to outcome manifest by increased frequency of
      shock and death from shock. This finding is in sharp contrast to the protective
      effects of induced hypothermia in septic animals and perhaps man.

PMID- 1395660
TI  - Effect of hypothermia on the coagulation cascade.
AB  - BACKGROUND AND METHODS: The development of a multifactorial coagulopathy after
      massive transfusion is a well-recognized clinical problem that is almost always
      accompanied by hypothermia. The purpose of this study was to investigate the
      isolated effect of alterations of temperature on the integrity of the coagulation
      cascade. Prothrombin times and partial thromboplastin times were each performed
      15 times on samples of pooled normal plasma at the temperatures of 37 degrees C,
      34 degrees C, 31 degrees C, and 28 degrees C, as well as 39 degrees C and 41
      degrees C. RESULTS: Mean prothrombin time results increased from 11.8 +/- 0.3
      (SD) secs at 37 degrees C to 12.9 +/- 0.5, 14.2 +/- 0.5, and 16.6 +/- 0.2 secs at
      34 degrees C, 31 degrees C, and 28 degrees C, respectively (p < or = .001 for
      each). Partial thromboplastin time determinations increased from 36.0 +/- 0.7
      (SD) secs at 37 degrees C to 39.4 +/- 1.0, 46.1 +/- 1.1, and 57.2 +/- 0.6 secs at
      34 degrees C, 31 degrees C, and 28 degrees C, respectively (p < or = .001 for
      each). Both prothrombin time and partial thromboplastin time determinations were
      only minimally shortened at hyperthermic temperatures. CONCLUSIONS: The series of
      enzymatic reactions of the coagulation cascade are strongly inhibited by
      hypothermia, as demonstrated by the dramatic prolongation of prothrombin time and
      partial thromboplastin time tests at hypothermic deviations from normal
      temperature in a situation where factor levels were all known to be normal.
      Clinicians who deal with critically ill massively transfused hypothermic patients
      all recognize the inevitable appearance of a coagulopathy that has a
      multifactorial origin. Unless specifically considered, the contribution of
      hypothermia to the hemorrhagic diathesis may be overlooked since coagulation
      testing is performed at 37 degrees C, rather than at the patient's actual in vivo
      temperature.

PMID- 1395661
TI  - Respiratory syncytial virus morbidity and mortality estimates in congenital heart
      disease patients: a recent experience.
AB  - OBJECTIVE: To determine recent morbidity and mortality rates from respiratory
      syncytial virus infection in a pediatric congenital heart disease population.
      DESIGN: Retrospective cohort study design. SETTING: The C. S. Mott Children's
      Hospital, University of Michigan Medical Center. PATIENTS: A total of 740
      pediatric patients hospitalized at the University of Michigan Medical Center for
      symptomatic respiratory syncytial virus infection, of whom, 79 patients had
      clinically important congenital heart disease. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: We retrospectively examined the charts of 740 patients
      hospitalized at our children's hospital from July 1, 1983 to June 30, 1990 with
      symptomatic respiratory syncytial virus infection to assess morbidity and
      mortality outcomes. Seventy-nine patients had congenital heart disease and 40 of
      these patients had pulmonary hypertension. For the entire cohort and a subset of
      patients with community-acquired infection, those patients with congenital heart
      disease had longer durations of hospitalization and greater need for, and days
      of, both intensive care and mechanical ventilation than patients without
      congenital heart disease. Mortality risk for respiratory syncytial virus
      community-acquired infection was not different for congenital heart disease vs.
      noncongenital heart disease patients (0.0% vs. 0.2%; p = 1.00). When examining
      only patients with congenital heart disease, those patients with pulmonary
      hypertension had increased hospital days and greater intensive care and
      mechanical ventilation durations compared with patients without this diagnosis.
      The overall mortality rate was low and was equally low for congenital heart
      disease groups with or without pulmonary hypertension (2.5 vs. 2.6). For
      community-acquired illness, no mortality was found in either congenital heart
      disease group. When the cohort of congenital heart disease patients was divided
      into pre- and postribavirin administration eras, no differences in mean hospital
      duration, ICU days, and mechanical ventilation days were noted. Of the 79
      congenital heart disease patients, only two died during their hospitalization in
      which respiratory syncytial virus infection occurred. Both patients had
      nosocomial-acquired respiratory syncytial virus and both were from the
      postribavirin administration cohort. One of these two patients had received
      antiviral therapy. Neither death was secondary to respiratory syncytial virus
      respiratory failure (based on pathologic examination). CONCLUSIONS: We conclude
      that respiratory syncytial virus mortality risk in pediatric patients with
      congenital heart disease is less than the risk reported a decade ago. Respiratory
      syncytial virus infection in congenital heart disease patients with pulmonary
      hypertension is associated with increased morbidity but not increased mortality
      rates. The markedly decreased respiratory syncytial virus mortality risk in
      patients with congenital heart disease currently experienced is likely secondary
      to improvements in intensive care management and advances in the surgical
      correction in this population rather than antiviral therapy.

PMID- 1395662
TI  - Circulating interleukin-1 beta and tumor necrosis factor-alpha concentrations
      after burn injury in humans.
AB  - OBJECTIVES: To measure plasma interleukin-1 beta (IL-1 beta) and tumor necrosis
      factor-alpha (TNF alpha) concentrations after burn injury and to determine if
      these concentrations relate to clinical status. DESIGN: Prospective assessment.
      SETTING: Hospital burn unit. PATIENTS: Thirty-one patients with second- or third
      degree burns, covering 10% to 95% of body surface area. MEASUREMENTS AND MAIN
      RESULTS: Initial concentrations of IL-1 beta were increased (mean 188 +/- 31
      pg/mL), and the concentrations for each patient correlated with body temperature
      at the time of the blood sample (rho = 0.51, p < .015) (rho is a nonparametric
      statistical measure; a nonparametric analysis is mandatory for data that is
      categorical [Acute Physiology and Chronic Health Evaluation, APACHE, scores] and
      data that are not normally distributed [IL-1 beta and tumor necrosis factor, TNF,
      data]). Mean TNF alpha concentrations were initially 264 +/- 132 pg/mL, and these
      concentrations were positively related to body temperature (rho = 0.41, p < .05)
      and inversely related to the total WBC count (rho = -0.45, p < .025). Through the
      course of hospitalization, plasma cytokine levels fluctuated, but transient
      increases (sometimes into the nanogram/mL range) did not consistently correspond
      to changes in clinical signs or severity of illness, as determined by APACHE II
      scores. The maximum plasma cytokine levels in any patient were not related to
      age, but maximum IL-1 beta concentrations were inversely related to burn size
      (rho = -0.46, p < .015). The final IL-1 beta concentrations measured in the
      patients who died (n = 7) were significantly less than measurements in surviving
      patients matched for burn size and age taken at approximately the same time after
      admission. CONCLUSIONS: These results indicate that early after burn injury there
      is a correspondence of IL-1 beta and TNF alpha with certain host responses, but
      these correlations disappear with the progression of illness. In general, IL-1
      beta and TNF alpha appear to be poor indicators of prognosis during burn injury;
      however, the association of mortality with low circulating IL-1 beta values
      supports the concept of IL-1 beta as being an essential mediator of host
      defenses.

PMID- 1395663
TI  - Myocardial metabolism and adaptation during extreme hemodilution in humans after
      coronary revascularization.
AB  - OBJECTIVE: This study was designed to evaluate the oxygen transport adjustments
      and myocardial metabolic adaptation that occurs with different levels of
      hemodilution during normothermia after cardiopulmonary bypass. DESIGN:
      Prospective, nonrandomized study. SETTING: Operating room in a university
      hospital. PATIENTS: Eight patients with ejection fractions (> 40%) undergoing
      elective coronary artery bypass grafting. METHODS: Before the institution of
      cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit
      of 15%. After coronary artery bypass grafting, a catheter was inserted directly
      into the coronary sinus. After the patients were rewarmed to 37 degrees C, they
      were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as
      well as measurements of myocardial oxygen consumption (VO2) and myocardial
      metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements
      were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was
      increased by autologous blood transfusion. MEASUREMENTS AND MAIN RESULTS: The
      three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/-
      4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p <
      .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350
      mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly
      after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7
      mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4
      +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also
      true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release
      were normal and unchanged at each level of hemodilution. Systemic oxygen
      extraction ratio increased with hemodilution and decreased with autologous
      transfusion. CONCLUSIONS: Hemodilution to a hematocrit of approximately 15% is
      tolerated in anesthetized humans after coronary artery bypass surgery. There was
      no evidence of myocardial ischemia, as demonstrated by absence of S-T depression
      on the electrocardiogram, lactate extraction, or hypoxanthine release. In
      selected patients, postoperative transfusion may be based on systemic physiologic
      end-points, such as oxygen extraction ratio, rather than set hematocrit values.

PMID- 1395664
TI  - Infectious and mechanical complications of central venous catheters placed by
      percutaneous venipuncture and over guidewires.
AB  - OBJECTIVE: To compare the frequency of infectious and mechanical complications of
      central venous and pulmonary artery catheters placed by initial venipuncture vs.
      over a guidewire at existing sites. HYPOTHESIS: Exchange of central venous
      catheters and pulmonary artery catheters over a guidewire as opposed to fresh
      venipuncture reduces mechanical complications without increasing risk of
      infection. DESIGN: Chart audit. PATIENTS: Medical, surgical, and coronary ICU
      patients requiring invasive monitoring or central venous access. INTERVENTIONS:
      Patients requiring prolonged catheterization underwent periodic exchange of
      catheters over a guidewire. Rates of catheter-related infections and mechanical
      complications were determined for central venous catheters placed by initial
      venipuncture and those catheters placed by guidewire exchange. MEASUREMENTS AND
      MAIN RESULTS: Over a 12-month period, 939 catheters were inserted in 454
      patients. Of these 939 catheters, 534 were placed by guidewire exchange. Use of a
      guidewire was associated with a decreased frequency of pneumothorax and
      hemothorax compared with initial venipuncture (0/405 [0%] vs. 7/534 [1.3%],
      respectively; p < .05) but not with increased risk of infection (9/405 [2.2%] vs.
      14/534 [2.6%], respectively; NS). Guidewire-facilitated replacement of multiple
      consecutive catheters at the same site did not increase the risk of catheter
      related infection. Catheters placed via internal jugular veins were more likely
      to become infected than catheters placed via subclavian veins (17/477 [3.6%] vs.
      3/430 [0.7%], respectively; p < .01). CONCLUSIONS: When prolonged central venous
      or pulmonary artery catheterization is necessary, periodic catheter replacement
      over a guidewire is associated with fewer mechanical complications than initial
      venipuncture. Periodic catheter replacement over a guidewire is also associated
      with no increase in risk of infection.

PMID- 1395665
TI  - Fibrinolytic activity in bronchoalveolar lavage of baboons with diffuse alveolar
      damage: trends in two forms of lung injury.
AB  - BACKGROUND AND METHODS: Alveolar fibrin deposition is prominent in diffuse
      alveolar damage, the morphologic hallmark of the adult respiratory distress
      syndrome. To determine if a persistent abnormality of fibrin clearance occurs in
      the alveolar compartment during evolving diffuse alveolar damage, we
      characterized abnormalities of fibrin turnover in serial bronchoalveolar lavage
      specimens from two baboon models: a) diffuse alveolar damage induced by 80%
      oxygen and bronchoscopic seeding of Pseudomonas aeruginosa; and b) a more
      fulminant form of diffuse alveolar damage induced by bronchoscopic seeding of
      Pseudomonas and the infusion of oleic acid. RESULTS: Lavage procoagulant
      activity, due mainly to tissue factor associated with Factor VII, was increased
      and exceeded regulation by extrinsic pathway inhibitor in both models.
      Fibrinolytic activity was transiently diminished in baboons with evolving diffuse
      alveolar damage induced by oleic acid/Pseudomonas, but was preserved after 80%
      oxygen/Pseudomonas. Concentrations of plasminogen activator inhibitor-2 did not
      increase in lavage specimens obtained during evolving diffuse alveolar damage.
      Concentrations of alpha 2 antiplasmin and plasminogen activator inhibitor-1
      tended to be higher in the lavage of oleic acid/Pseudomonas baboons with low
      fibrinolytic activity. Immunohistochemical analyses showed that tissue factor was
      distributed along the alveolar surface of controls and baboons with diffuse
      alveolar damage. Alveolar fibrin deposition was increased, by morphometric
      analyses, in both models. CONCLUSIONS: These data indicate that while increased
      procoagulant activity is characteristic of evolving diffuse alveolar damage and
      favors alveolar fibrin deposition, fibrinolytic activity may be transiently
      diminished or remain intact during evolving diffuse alveolar damage in baboons.

PMID- 1395666
TI  - Increased antioxidant activity in bronchoalveolar lavage fluid after acute lung
      injury in anesthetized sheep.
AB  - OBJECTIVE: To determine if bronchoalveolar lavage fluid is a more potent
      antioxidant after acute lung injury in a sheep model compared with the baseline
      condition. DESIGN: Nonrandomized, controlled study, with repeated measures.
      SETTING: University research laboratory. SUBJECTS: Seven healthy adult sheep (25
      to 50 kg) were studied with five experimental sheep and two control sheep.
      INTERVENTIONS: Sheep with lung-lymph fistulas were used to study the antioxidant
      activity of serum, lymph, and bronchoalveolar lavage fluid, both at baseline and
      after the iv infusion of endotoxin and subsequent induction of acute lung injury.
      Antioxidant activity was measured, and it reflects the ability of serum, lymph,
      and bronchoalveolar lavage fluid to inhibit lipid peroxidation. MEASUREMENTS AND
      MAIN RESULTS: When compared at several volumes, bronchoalveolar lavage fluid
      after acute lung injury was a more potent inhibitor of lipid peroxidation than
      bronchoalveolar lavage fluid at baseline. In contrast, antioxidant activity in
      both serum (69.6 +/- 4.5% vs. 47.2 +/- 4.6%; p = .001) and lymph (45.0 +/- 2.3%
      vs. 31.9 +/- 1.2%; p = .001) decreased with acute lung injury. CONCLUSIONS: These
      findings suggest that the alveolar fluid after acute lung injury possesses
      enhanced antioxidant activity that is likely due to the influx of serum proteins.
      Thus, the high permeability pulmonary edema of acute lung injury, while
      detrimental to gas exchange, may be beneficial in preventing further oxidant
      mediated lung injury.

PMID- 1395667
TI  - Pluronic F 127 liquid sensitizes mice to low doses of Escherichia coli
      lipopolysaccharide.
AB  - BACKGROUND AND METHODS: In murine models of endotoxemia, large amounts of
      lipopolysaccharide have to be administered to induce mortality. If mice are
      pretreated with D-galactosamine, the amount of lipopolysaccharide required to
      induce mortality is significantly lowered. Pluronic F 127 liquid is a relatively
      non-toxic copolymer that exhibits reverse gelation properties. Thus, it is a
      liquid at cold temperature and a gel at body temperature. The present studies
      were performed to ascertain whether the reverse gelation properties of Pluronic F
      127 liquid could be used in devising a model of septic shock where a sustained
      delivery of lipopolysaccharide occurred. In evaluating this model, dose-response
      studies were conducted with lipopolysaccharide when a) it was administered
      intraperitoneally in saline or in Pluronic F 127 liquid, and b) it was
      administered intravenously to mice that had been pretreated with saline or
      Pluronic F 127 liquid. Mortality was followed for up to 72 hrs. RESULTS: Various
      doses of Escherichia coli lipopolysaccharide dissolved in saline or in Pluronic F
      127 liquid were administered intraperitoneally to mice. The lethal dose of
      lipopolysaccharide required to kill 50% of the mice (LD50) administered in
      Pluronic F 127 liquid was approximately ten- to 15-fold less than the values
      obtained for lipopolysaccharide administered in saline. This decrease in the LD50
      of lipopolysaccharide was also observed if the mice were treated
      intraperitoneally with Pluronic F 127 liquid and challenged 6 hrs later with iv
      lipopolysaccharide. The concentrations of tumor necrosis factor and interleukin-6
      in the plasma were significantly higher when a low dose of lipopolysaccharide was
      administered to mice that had been pretreated with Pluronic F 127 liquid. While
      there was no effect on the liver enzymes, Pluronic F 127 liquid caused an
      increase in the plasma triglycerides. CONCLUSIONS: The data reported in this
      paper indicate that the LD50 of lipopolysaccharide is significantly decreased if
      it is administered in Pluronic F 127 liquid or administered to mice that have
      been pretreated with the Pluronic F 127 liquid. Thus, Pluronic F 127 liquid
      appears to sensitize mice to low levels of lipopolysaccharide. Unlike the D
      galactosamine model, lipopolysaccharide can be administered as late as 6 hrs
      after treatment with Pluronic F 127 liquid. While the mechanisms by which
      Pluronic F 127 liquid sensitizes mice is not known, plasma triglycerides were
      increased in mice treated with this agent, suggesting that tissues responsible
      for the synthesis and/or degradation of triglycerides play a role in this
      sensitization process.

PMID- 1395668
TI  - Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in
      sheep.
AB  - BACKGROUND AND METHODS: Critically ill infants undergoing extracorporeal membrane
      oxygenation (ECMO) therapy often receive multiple pharmacologic agents. Although
      the disposition of many drugs has been assessed in patients undergoing
      cardiopulmonary bypass and in patients receiving mechanical ventilation, only
      limited data exist for selected medications in patients undergoing ECMO. To
      evaluate the potential influence of ECMO on aminoglycoside pharmacokinetics, we
      studied the disposition of tobramycin in ten sheep before and during ECMO
      therapy. Each sheep received a single iv dose of tobramycin during a control
      period before ECMO and on a study day during ECMO. Identically timed serial blood
      samples over 4 hrs were obtained after each tobramycin dose. Paired serum
      tobramycin concentrations were obtained pre- and postmembrane oxygenator during
      ECMO in six sheep. RESULTS: Alterations in specific pharmacokinetic variables for
      tobramycin were observed as a result of ECMO. Estimates of elimination half-life
      and volume of distribution for tobramycin were significantly increased during
      ECMO as compared with control (pre-ECMO) values (1.8 +/- 0.3 vs. 2.7 +/- 0.8 [SD]
      hrs [p < .01] and 0.3 +/- 0.1 vs. 0.5 +/- 0.2 L/kg [p < .005], respectively).
      Tobramycin body clearance was unaffected by the procedure (1.8 +/- 0.8 vs. 1.7 +/
      0.4 mL/min/kg). Paired serum tobramycin concentrations obtained pre- and
      postmembrane oxygenator demonstrated no drug removal. CONCLUSIONS: These data
      suggest that ECMO circuitry does not sequester tobramycin and that the prolonged
      elimination half-life observed during ECMO therapy is not due to a change in drug
      clearance but is due to an ECMO-induced increase in tobramycin volume of
      distribution. To achieve and maintain preselected target tobramycin serum
      concentrations during ECMO, the usual dosage interval should remain unchanged,
      but the dose should be increased to compensate for the alteration in the drug's
      volume of distribution. The clinical applicability of these findings needs to be
      confirmed in carefully controlled clinical studies involving infants receiving
      ECMO therapy.

PMID- 1395669
TI  - Are ejection fractions based on regression equations for systolic time ratios
      reliable?

PMID- 1395670
TI  - Mean airway pressure: physiologic determinants and clinical importance--Part 1:
      Physiologic determinants and measurements.
AB  - PURPOSES: To discuss the theoretical relationship of mean alveolar pressure to
      its most easily measured analog, the mean airway pressure, and to describe the
      key determinants, measurement considerations, and clinical implications of this
      index. DATA SOURCES: Relevant articles from the medical and physiologic
      literature, as well as mathematical arguments developed in this article from
      first principles. STUDY SELECTION: Theoretical, experimental, and clinical
      information that elucidates the physiologic importance, measurement, or adverse
      consequences of mean airway pressure. DATA EXTRACTION: Mathematical models were
      used in conjunction with data from the published literature to develop a unified
      description of the physiological and clinical relevance of mean airway pressure.
      SYNTHESIS: Geometrical and mathematical analyses demonstrate that shared elements
      comprise mean airway pressure and mean alveolar pressure, two variables that are
      related by the formula: mean alveolar pressure = mean airway pressure + (VE/60) x
      (RE-RI), where VE, RE, and RI are minute ventilation and expiratory and
      inspiratory resistances, respectively. Clear guidelines can be developed for
      selecting the site of mean airway pressure determination, for specifying
      technical requirements for mean airway pressure measurement, and for delineating
      clinical options to adjust the level of mean airway pressure. Problems in viewing
      mean airway pressure as a reflection of mean alveolar pressure can be interpreted
      against the theoretical basis of their interrelationship. In certain settings,
      mean airway pressure closely relates to levels of ventilation, arterial
      oxygenation, cardiovascular function, and barotrauma. Because mean airway
      pressure is associated with both beneficial and adverse effects, a thorough
      understanding of its theoretical and practical basis is integral to formulating
      an effective pressure-targeted strategy of ventilatory support. CONCLUSIONS: Mean
      airway pressure closely reflects mean alveolar pressure, except when flow
      resistive pressure losses differ greatly for the inspiratory and expiratory
      phases of the ventilatory cycle. Under conditions of passive inflation, mean
      airway pressure correlates with alveolar ventilation, arterial oxygenation,
      hemodynamic performance, and barotrauma. We encourage wider use of this index,
      appropriately measured and interpreted, as well as its incorporation into
      rational strategies for the ventilatory management of critical illness.

PMID- 1395671
TI  - Care of the dying: an ethical and historical perspective.
AB  - OBJECTIVE: To provide a historical perspective, from ancient Greece to the middle
      of the 20th century, on ethical issues and principles commonly associated with
      medical care for the dying in Western civilization. SOURCES: Writings of noted
      philosophers, historians, ethicists, and physicians, as well as published legal
      and ethical guidelines. INFORMATION EXTRACTION: The sources used highlight the
      origins of various ethical principles associated with care of the dying. They
      also identify the opinions of prominent individuals throughout the history of
      medical ethics. SUMMARY: Devotion to medical beneficence, concern for the quality
      of life, and respect for the sanctity of life are all expressed in the earliest
      medical and philosophical writings of ancient Greece. With regard to care of the
      dying, these considerations led to a wide acceptance of avoiding or terminating
      treatment in hopeless cases. They also led to active debate regarding medicine's
      role in hastening the dying process. The rise of Christianity during the Middle
      Ages markedly suppressed such debate by strongly reinforcing the principle of
      sanctity of life. Later, the optimism of the enlightenment added the hope of
      prolonging life. Finally, modern advances in medical science have made that hope
      a reality of complex ethical dimensions. CONCLUSIONS: Ethical debates regarding
      appropriate care for the dying are as old as medicine itself. Although beneficent
      concerns have characterized the medical community in almost every period of
      history, tensions have repeatedly arisen as diverse religious and philosophical
      ideologies have produced varying standards to define such beneficence. In the
      Christian world, the sanctity of life was often extolled as the paramount
      standard. For the ancient Greeks and Romans, and again in many post-Renaissance
      philosophies, quality of life considerations assumed equal or greater importance.
      Modern life-prolonging technologies heighten the debate by allowing these two
      standards to dramatically conflict, particularly in the critical care setting.

PMID- 1395672
TI  - Increased plasma tumor necrosis factor concentration in severe rhabdomyolysis is
      not reduced by continuous arteriovenous hemodialysis.

PMID- 1395673
TI  - Survival after 67 days of continuous hemodiafiltration in a patient with multiple
      system organ failure.

PMID- 1395674
TI  - Rapid neutrophil recovery from acquired agranulocytosis by recombinant human
      granulocyte-macrophage colony-stimulating factor in an intensive care patient.

PMID- 1395675
TI  - Tension pneumomediastinum complicating Pneumocystis carinii pneumonia in acquired
      immunodeficiency syndrome.

PMID- 1395676
TI  - Glasgow Meningococcal Septicemia Prognostic Score in meningococcal septicemia.

PMID- 1395677
TI  - Manual resuscitators and spontaneous ventilation--an evaluation.

PMID- 1395678
TI  - Neurologic complications secondary to internal jugular vein cannulation.

PMID- 1395679
TI  - Negative inotropism of pentoxifylline.

PMID- 1395681
TI  - In memoriam Edmund Fay Graham (1924-1991).

PMID- 1395680
TI  - Lidocaine in continuous venovenous hemofiltration.

PMID- 1395682
TI  - Effects of dimethyl sulfoxide on cultured rat hepatocytes in sandwich
      configuration.
AB  - A recently developed sandwich culture system, in which hepatocytes are sandwiched
      between two layers of collagen, has been shown to be capable of maintaining long
      term expression of hepatocellular function (J. C. Y. Dunn et al., Biotechnol.
      Prog. 7, 237-245, 1991). The development of an adequate technique for the
      cryopreservation of hepatocytes in such a stable culture configuration would
      ensure a ready supply of hepatocytes for use in bioreactors or bioartificial
      liver support devices. This report describes the effects of exposing hepatocytes
      in sandwich culture to different concentrations of the cryoprotectant dimethyl
      sulfoxide (Me2SO) at 22 degrees C on Day 7 of culture. Cell function, morphology,
      and cytoskeletal organization were followed for 14 days after exposure.
      Hepatocellular morphology and albumin secretion remained normal when cultures
      were exposed for up to 120 min to predicted final Me2SO concentrations up to 1.33
      M. Exposure for less than 60 min to equilibrium concentrations of up to 3.33 M
      Me2SO did not adversely affect cell morphology or albumin secretion rate, but at
      the highest concentration (3.33 M), increase of the exposure time to 60 or 120
      min resulted in dramatic, irreversible cell damage and loss of function. Actin
      filament organization was shown to be undisturbed when the cells were exposed to
      1.33 M Me2SO for 60 min, but was irreversibly disrupted by exposure to 3.33 M for
      120 min. Based on these results, a simple and safe procedure is suggested for the
      addition of Me2SO to hepatocytes in a sandwich culture configuration and its
      subsequent removal, which will be valuable for studies on hepatocyte
      cryopreservation.

PMID- 1395683
TI  - Thawed human hepatocytes in primary culture.
AB  - In drug metabolism studies, isolated and cultured human hepatocytes provide a
      useful model for overcoming the difficulty of extrapolating from animal data. In
      vitro studies with human hepatocytes are scarce because of the lack of livers and
      suitable methods of storage. After developing a new method for cryopreservation
      of human hepatocytes, we evaluated the effects of deep freezing storage on their
      viability, morphology, and functional and toxicological capabilities in classical
      culture conditions. Freshly isolated human hepatocytes were cryopreserved in
      medium containing 10% Me2SO and 20% fetal calf serum, using a Nicool ST20
      programmable freezer (-1.9 degrees C/min for 18 min and -30 degrees C/min for 4
      min). Cells were stored in liquid nitrogen. Viability of thawed human hepatocytes
      was 50-65% as assessed by erythrosin exclusion test prior to purification on a
      Percoll density gradient. Morphological criteria showed that thawed human
      hepatocytes require an adaptation period to the medium after seeding. Functional
      assessments showed that human hepatocytes which survive freezing and thawing
      preserve their protein synthesis capabilities and are able to secrete a specific
      protein, anionic peptidic fraction, which is involved in the hepatic uptake of
      bile-destined cholesterol. We then studied Midazolam biotransformation to test
      metabolic functions, and erythromycin toxicity by Neutral Red test (cell
      viability) and 3-(4,5-dimethylthiazol-2-yl)-diphenyl tetrazolium bromide test
      (cell metabolism). All of these experiments indicated that thawed human
      hepatocytes should be used 38 h after seeding for optimum recovery of their
      functions: membrane integrity, protein synthesis, and stabilization of drug
      metabolism enzymes.

PMID- 1395684
TI  - Freezing preservation of the mammalian cardiac explant. V. Cryoprotection by
      ethanol.
AB  - We studied the colligative cryoprotective effect of ethanol (EtOH) in preserving
      the isolated rat heart frozen at -3.4 degrees C or unfrozen at -1.4 degrees C.
      Addition of 4.7% (v/v) EtOH to a cardioplegic solution, CP-14, raised the
      osmolality from 280 to 1100 mOsm/kg H2O and lowered the melting point from -0.52
      to -2.1 degrees C. Freezing of the cardiac explant at -3.4 degrees C for 6 h
      resulted in 34.3 +/- 1.9% of the tissue water as ice; recovery of cardiac output
      (CO) was 50%. Polyethylene glycol, which at 5% (w/v) has been shown to
      cryoprotect the hearts during freezing at -1.4 degrees C, did not improve the
      protective effect of 4.7% EtOH. CP-14 + 4.7% EtOH did not freeze at -1.4 degrees
      C. After 6 h storage, CO in hearts flushed with CP-14 + 4.7% EtOH oxygenated with
      95% O2/5%CO2 returned to almost control level and was much higher than that in
      hearts flushed with 100% O2 saturated-CP-14 + 4.7% EtOH. Storage of 8 and 12 h
      reduced CO to 87 +/- 9 and 60 +/- 5% of control. By employing EtOH as a
      colligative cryoprotectant, we preserved the adult mammalian heart frozen at -3.4
      degrees C or unfrozen at -1.4 degrees C, suggesting that this small molecular
      weight, penetrating substance may be a suitable cryoprotectant for long-term
      storage of the cardiac explant at high subzero temperatures.

PMID- 1395686
TI  - In vitro fertilization and development of frozen-thawed bovine oocytes.
AB  - Bovine oocytes were vitrified (V-oocytes) or frozen slowly (S-oocytes) at the
      germinal vesicle (GV) stage or after maturation in vitro (IVM) and their survival
      assessed morphologically and also by in vitro fertilization (IVF) and culture.
      The morphological survival of S-oocytes was 30.7% after freezing at the GV stage
      and 53.3% after IVM. The corresponding survival rates of V-oocytes were
      significantly lower, viz. 14.6 and 14.0%, respectively. The fertilization rate of
      S-oocytes frozen after IVM (51.0%) was lower than that of unfrozen controls
      (75.8%), but higher than after other treatments. Development continued in 16.0%
      of the fertilized S-oocytes, compared to 39.4% of control IVF zygotes and 1.6%
      developed into morulae or blastocysts (4.5% in controls). Only 0.8% of frozen
      thawed GV stage oocytes and 4.6% of post-IVM V-oocytes cleaved after IVF and none
      formed morulae or blastocysts. Transfer of four embryos (two morulae and two
      blastocysts) derived from post-IVM S-oocytes into a recipient heifer resulted in
      pregnancy and the birth of twin calves.

PMID- 1395685
TI  - Freezing preservation of the mammalian cardiac explant. VI. Effect of thawing
      rate on functional recovery.
AB  - This study investigated the effect of thawing rate on the preservation of frozen
      isolated rat hearts. The hearts were flushed with a hyperosmotic cardioplegic
      solution, CP-14/EtOH (1.15 Osm/kg), frozen at a rate of 0.18 degree C/hr for 6 h
      to -3.2 degrees C. Thereafter, the hearts were thawed at rates ranging from 0.08
      to 1.1 degrees C/min for 1 to 14 min until the heart temperature reached -2.1
      degrees C, the melting point (MP) of the flush solution; then they were held at 
      1 degree C for 11 to 24 min so that the total thaw time was 25 min. Post-thaw
      function was assessed by working reperfusion and expressed as percentage of
      unstored control function. Cardiac output (CO) and other hemodynamic performance
      showed biphasic responses to the thaw rate. At 0.08 degree C/min rate, CO
      recovered to 29.1 +/- 4.1 ml/min (40.8 +/- 5.8% of control). Thawing at 0.13
      degree C/min enhanced the recovery of CO to 60.5 +/- 4.9%. Between 0.13 and 0.34
      degree C/min, recovery was statistically insignificant. Faster thawing at 0.59
      and 1.1 degrees C/min caused progressively less recovery. Overall, 0.13 degree
      C/min offered the highest recovery. In conclusion, function in slowly frozen
      heart is intimately affected by the thawing rate; there was an optimal
      intermediate thawing rate and both too slow and too fast thawing were
      detrimental.

PMID- 1395687
TI  - Viability of nuclei of two-cell mouse embryos stored at 4 degrees C and fused
      with blastomeres of fresh two-cell embryos.
AB  - This study compares the resistance of the nuclei and the cytoplasm of two-cell
      mouse embryos to short-term storage at low temperature above 0 degrees C. Two
      cell embryos were stored at 4 degrees C for 24-96 h in PB1 containing 0.25, 0.5,
      0.75, and 1.0 M sucrose. The development to blastocysts in culture was highest in
      the presence of 0.5 M sucrose. However, only 3% of the embryos developed into
      blastocysts after 96 h of storage. On the other hand, the viability of the nuclei
      of two-cell embryos stored at 4 degrees C was significantly prolonged when they
      were transplanted into a blastomere of enucleated fresh F1 (C57BL/6JXCBA) two
      cell embryos. The proportions of chimeric embryos that developed to blastocysts
      were 88, 67, 76, 71, 64, 45, 32, and 20% following storage for 0, 48, 72, 96,
      120, 144, 168, and 192 h, respectively. In addition, there was no difference in
      the coat color of the young derived from nuclei stored at 4 degrees C or fresh
      nuclei, although the proportions of chimeric embryos that developed into live
      young after transfer tended to decrease with increased storage time. Moreover,
      the viability of nuclei stored at 4 degrees C for 192 h was confirmed in the germ
      cell population of chimeric mice mated with albino mice. These results
      demonstrated that the nuclei in the two-cell mouse embryos were more resistant to
      storage at low temperature than the cytoplasm.

PMID- 1395688
TI  - Cryoinjury in human granulocytes and cytoplasts.
AB  - Although most isolated cells can be successfully cryopreserved, human
      granulocytes have little functional recovery after cryopreservation, even under
      optimized conditions. Cytoplasts, which are vesicles created from human
      granulocytes by depletion of organelles including granules and the nucleus, can
      carry out some of the complex functions of the parent granulocyte such as
      phagocytosis of bacteria, even after cryopreservation. Human granulocytes and
      cytoplasts were used in this comparative study of low-temperature responses to
      assess the relative importance of the plasma membrane and the granules in
      cryoinjury to human granulocytes. Boyle-van't Hoff plots of cell volume as a
      function of the reciprocal of osmolality showed that granulocytes and cytoplasts
      have similar osmometric behavior and equivalent osmotically inactive fractions.
      The hydraulic conductivities were also similar, indicating that the osmotic
      properties of the plasma membrane and cytoplasm were retained during preparation
      of the cytoplasts. Assessment of membrane integrity using fluorescein diacetate
      after graded freezing stresses showed that the low-temperature responses of
      cytoplasts were similar to those of human lymphocytes and hamster fibroblasts,
      with recoveries much higher than those of human granulocytes, particularly after
      post-thaw incubation at 37 degrees C. The results indicate that the plasma
      membrane is not the primary site of injury to granulocytes during freezing and
      thawing, and suggest that activation of cytoplasmic elements, such as granules,
      may constitute the early events in cryoinjury to human granulocytes. These
      studies have significance in approaches to the cryopreservation of granulocytes
      and other types of cells, such as platelets, with increased sensitivity to the
      conditions encountered during freezing and thawing.

PMID- 1395689
TI  - Cryoprotection of purified rat kidney transamidinase by polyethylene glycol.
AB  - Polyethylene glycol is a water-soluble polymer which is widely used in the
      pharmaceutical, cosmetic, and chemical industries. In this study, it is shown
      that polyethylene glycol is an effective cryoprotectant of rat kidney
      transamidinase purified from both the mitochondria and cytosol. Much of the
      activity is lost when the purified enzyme is frozen and thawed in sodium
      potassium phosphate buffer in the absence of cryoprotectants. Polyethylene
      glycols with molecular weights of 4000 to 10,000 were effective cryoprotectants.
      However, polyethylene glycols with a molecular weight of 1000 or lower inhibited
      the purified enzyme. A concentration of only 0.01% polyethylene glycol 4000,
      8000, or 10,000 was required for complete cryoprotection. In addition to
      polyethylene glycol, 0.5 mM ethylenediaminetetraacetic acid was required in the
      phosphate buffer for complete cryoprotection. The stabilization of purified
      transamidinase by polyethylene glycol will facilitate characterization
      experiments designed to compare the properties of the mitochondrial and cytosolic
      isozymes.

PMID- 1395690
TI  - The role of freezing in trypsin activity oscillations.
AB  - The importance of the frozen phase in the formation of cryooscillations of
      trypsin activity has been shown in experiments conducted at -10 degrees C under
      frozen and supercooled conditions, respectively. A solution containing trypsin
      obtained by trypsinogen activation and 0.1 M MnCl2 was distributed in test tubes
      with or without previous freezing and kept at -10 degrees C and pH 8.4. At given
      time intervals the frozen and supercooled samples were tested simultaneously for
      tryptic activity. Although a temporal motion of trypsin activity was produced by
      the frozen samples, the activity of the supercooled samples began to oscillate
      only after spontaneous freezing of the solutions. This phenomenon suggests the
      importance of compartmentalization of the frozen heterogeneous system, which
      results in an increase in concentration vs a decrease in diffusion rate of the
      components.

PMID- 1395691
TI  - Viscosity of water in hibernating and nonhibernating mammals estimated by proton
      NMR relaxation times.
AB  - Longitudinal (T1) and transverse (T2) nuclear magnetic resonance relaxation times
      were measured in vitro at 37, 30, 25, 15, and 5 degrees C on serum, brain, liver,
      kidney, and heart samples from a hibernator, the European hamster, active in
      summer (SA), active in winter, or in the hibernating state in winter; from a less
      efficient hibernator, the golden hamster; and from a homeotherm, the rat. T1 and
      T2 relaxation times varied between species and in the European hamster between
      the active and hibernating subjects. Despite the major relaxation time
      differences between the organs, NMR relaxation time measurements showed a general
      trend to an increase in the viscosity of water for the European hamster in the
      active state. Although these modifications were not directly related to the
      process of hibernation itself, the relaxation times observed in the hibernating
      animals were closer to those seen in the rat. This evidenced that changes of
      physical properties of water reflect a better adaptation to low temperatures of
      the hamster, as compared to the nonhibernator, given that the low water viscosity
      of SA hamster allows the decrease of the viscosity with temperature during the
      hibernating state. These in vitro studies permit the study the viscosity which is
      an important physicochemical parameter involved in NMR longitudinal relaxation
      time of water proton. More detailed studies of other physiological parameters
      must be undertaken by further in vivo measurements.

PMID- 1395693
TI  - No aging in India: the uses of gerontology.
AB  - This paper develops a critique of international gerontology through an
      ethnography and analysis of gerontological practice in India. The central theme
      of Indian gerontology - that of an imminent demographic and social explosion of
      an aging population who will tax the country's slender resources - misrepresents
      available data and fails to signify the experience of most Indian old people.
      Narrative and deconstructive techniques are deployed to examine the language of
      crisis and the complex sources of this misrepresentation. Three sources are
      explored: local disjunctions of class and gender in India, neocolonial biases in
      the structure of knowledge on aging central to international discourse, and
      subaltern strategies within India for subverting Western and elite Indian
      imperatives of what it means to be old. A variety of textual, ethnographic, and
      historical materials are examined: Indian and American literature pertaining to
      the 1982 World Assembly on Aging, a series of sociological texts each entitled
      "Aging in India," and four contemporary Indian institutions designed to meet the
      needs of old people: a social service agency, a geriatric clinic, a retirement
      community, and an old age home.

PMID- 1395692
TI  - Protective action of aromatic compounds against cold-shock injuries in boar
      spermatozoa.
AB  - Butylated hydroxytoluene has been known to protect spermatozoa from cold shock
      injury. To determine whether such protective action is a common property of
      aromatic compounds, the effect of 14 hydrophobic and 2 hydrophilic aromatic
      compounds on the protection of boar spermatozoa from cold shock was investigated.
      The majority of the hydrophobic compounds tested provided protection; the
      hydrophilic compounds were ineffective. Of the aromatic compounds tested,
      naphthalene was most effective in reducing the effect of cold shock on motility
      and acrosomal integrity of boar spermatozoa.

PMID- 1395694
TI  - Pharmaceuticals as folk medicine: transformations in the social relations of
      health care in Uganda.
AB  - The deterioration of government health services in Uganda since 1971 has been
      accompanied by a process of privatization which has made pharmaceuticals readily
      available outside of biomedical institutions. On the basis of material from
      eastern Uganda, the article analyses this development in terms of the 'sector
      model' of health care systems, with special attention to the relations between
      the professional and folk sectors. Folk practitioners of pharmaceutical medicine
      include a broad range of specialists, from government trained paramedicals in
      private practice to vendors bringing medicine to local markets. Like other folk
      specialists, they respect the customer's opinion, provide treatment by proxy and
      adjust their services to the customer's ability to pay. Although there are
      negative aspects of this development, from the local point of view there are also
      positive ones, which deserve the consideration of health planners.

PMID- 1395695
TI  - Si dios quiere: Hispanic families' experiences of caring for a seriously mentally
      ill family member.
AB  - Among Hispanics, the family is viewed as the primary care giver for seriously
      mentally ill family members. This paper reports on a study of minority families'
      conceptions of serious mental illness, of their interaction with mental health
      resources, and on the burdens experienced by families in caring for a seriously
      mentally ill family member. The focus of this paper is on Hispanic families in
      New Jersey, with some comparative data from other ethnic group families.
      Families' conceptions of serious mental illness are explored and analyzed to
      demonstrate the importance of concepts of nervios and fallo mental in shaping
      families' responses to their ill family member. Social support systems for
      families are also explored with particular attention to the role of religious
      institutions and religious healing as a major source of solace.

PMID- 1395696
TI  - "Chronicity," "nervios" and community care: a case study of Puerto Rican
      psychiatric patients in New York City.
AB  - The role of ethnicity, community structure, and folk concepts of mental illness
      in facilitating the adaptation of long term psychiatric patients to community
      living has received little attention. This article examines the cultural concepts
      of mental illness and the community involvement of 30 Puerto Rican psychiatric
      patients participating in a New York City treatment program. It is shown that
      many of the attributes usually associated with chronic mental illness do not
      apply to this population. It is argued that the folk concept of nervios helps to
      foster the integration of these patients in a wide range of community networks.
      The impact of gentrification on these patients' community integration is also
      discussed.

PMID- 1395697
TI  - Controlling domestic life and mental illness: spiritual and aftercare resources
      used by Dominican New Yorkers.
AB  - This research addresses the differential use of spiritual and mental health
      resources by 15 Dominican migrant women with major psychiatric disorders in
      Northern Manhattan. Methods included interviews and participant observation with
      patients, kin, and mental health staff. Structured instruments were used to
      examine patients' networks and functioning. Folk and popular healing traditions,
      adopted by some patients and kin through private observances or through a
      connection with a healer, yielded symbolic supports, companionship for patients,
      and ways of communicating and coping with distress. Episodes of health-seeking
      revealed multiple participants competing for control of the patients' lives and
      illness careers. Consultations with healers offered family members potential
      mastery over illness and domestic life, with no surrender of centrality, dignity
      or control in the quest for care.

PMID- 1395698
TI  - Charisma, crowd psychology and altered states of consciousness.
AB  - This paper argues that an interpretive meaning-centered analysis is not adequate
      for understanding collective behavior that is outside the range of calculating
      rationality. Alternative approaches to collective irrational action are drawn
      from the work of Weber and Durkheim, as well as from the crowd psychologists Le
      Bon and Tarde. These approaches are then illustrated in a short analysis of the
      trajectories and recruitment techniques of two contemporary American religious
      annunications: est and Scientology, and the findings applied to the general
      social formation.

PMID- 1395699
TI  - Grief and rage: collective emotions in the politics of peace and the politics of
      gender in Israel.
AB  - Collective emotions of rage and grief dominate Israeli political discourses
      regarding the Middle East conflict. The weekly peace vigils of the Women in Black
      who protest the state's occupation of the West Bank and Gaza and the opposition
      which the vigils encounter, publicly display politicized collective emotions. In
      these weekly confrontations, grief and rage articulate intense contestations
      regarding the politics of peace as well as the politics of gender in Israel. Rage
      and grief unravel two drastically different visions of transcending national
      vulnerabilities and two disparate constructions of gender identity.

PMID- 1395700
TI  - Reflections on Tamazai, a Tuareg idiom of suffering.
AB  - In this essay, I explore ways in which the theatrical and the medical are
      inextricably mixed and affect each other, in the Nigerien Tuareg idiom of
      tamazai. Tamazai is locally-described as "an illness of the heart and soul, not
      curable by Koranic verses," but by exorcism of spirits. A case study and analysis
      of healing rituals demonstrate how this idiom communicates women's relationships
      and empowers dramatic framing.

PMID- 1395701
TI  - Ataques de nervios: proposed diagnostic criteria for a culture specific syndrome.
AB  - The authors propose a set of diagnostic criteria and report two cases of ataque
      de nervios, a syndrome of brief duration seen primarily in Spanish-speaking
      people of the Caribbean. Following a psychosocial stressor, the afflicted person
      demonstrates impulsivity, dissociation and communication and perceptual
      disturbances. The symptoms often begin in the presence of the family, allow a
      temporary relinquishing of social roles, and result in the mobilization of the
      social network in support of the person. Further research is needed to improve
      our understanding of this culture specific syndrome and its relationship to
      psychiatric disorder.

PMID- 1395703
TI  - Jail suicide--an overview of yesterday.

PMID- 1395704
TI  - Hotlines--our heritage and challenges.

PMID- 1395702
TI  - Transcultural aspects of eating disorders: a critical literature review.
AB  - A review of studies addressing anorexia nervosa and bulimia nervosa among Native
      Americans, African-Americans, Hispanics, Asians, Africans, and Middle Easterners
      yielded only 35 studies, of which 22 were qualitative case reports, three were
      clinical quantitative studies, and ten were non-clinical quantitative studies.
      The case studies reported symptoms similar to those of Caucasian patients, and
      eating disorders were reported in all SES classes. The clinical studies, all
      reported from Asian countries, described a number of cases for eating disorders
      quite different from one another. The non-clinical quantitative studies reported
      a number of cases consistent with the ranges previously reported for controlled
      samples of non-clinical Caucasian populations. We found few or no quantitative
      studies on eating disorders from Hispanic, Middle Eastern, African, or Asian
      countries other than Japan.

PMID- 1395705
TI  - The aftermath of youth suicide--providing postvention services for the school and
      community.
AB  - Suicide is one of the leading causes of death in adolescence. Due to the risk of
      contagion and maladaptive coping responses in the aftermath of suicide,
      clinicians have responded by developing postvention services. Based on a
      considerable amount of experience in this field, target groups of individuals
      have been identified to receive such assistance. These groups include school
      administrators, staff, students, families, and community members at large. In
      addition, it has become clear that the local media response to suicide is of
      critical importance, and that school administrators and local mental health
      officials should work effectively with reporters so that news stories do not
      contribute to suicide contagion.

PMID- 1395706
TI  - The Los Angeles Survivors-After-Suicide program. An evaluation.

PMID- 1395707
TI  - Psychoeducational intervention strategies for survivors of suicide.

PMID- 1395708
TI  - Research contributions to understanding the suicide survivor.

PMID- 1395709
TI  - Suicide in the elderly.

PMID- 1395710
TI  - Crisis-to-crisis management or crisis management.

PMID- 1395711
TI  - Recent developments in adolescent pregnancy.

PMID- 1395712
TI  - Cocaine, pregnancy, and the growing child.

PMID- 1395713
TI  - Somatic cell hybrid mapping of human chromosome band 5q31: a region important to
      hematopoiesis.
AB  - As a means of characterizing the distal long arm of chromosome 5, in particular,
      the region spanning 5q23-->q31, we analyzed somatic cell hybrids prepared from
      cells with overlapping chromosomal rearrangements. In one hybrid, the derivative
      chromosome 5 from a patient with acute myeloid leukemia (AML) de novo, whose bone
      marrow cells had a balanced translocation, t(5;7)(q31;q22), involving chromosome
      band 5q31, was isolated in a somatic cell hybrid (B294). In addition, we prepared
      somatic cell hybrids from a lymphoblastoid cell line (CC) derived from a patient
      who has a constitutional interstitial deletion of chromosome 5 spanning 5q23.1-
      >q31.1. By a combination of Southern hybridization analysis and fluorescent in
      situ hybridization, we constructed a map dividing 5q23-->q31 into four regions.
      We can assign genes to these regions and relate them to anonymous RFLP markers
      that have been genetically mapped.

PMID- 1395714
TI  - A second human ferritin H locus on chromosome 11.

PMID- 1395715
TI  - Isolation of new probes from Xq12-->q13: an example of the screening of reference
      libraries with Alu-PCR products from radiation hybrids.
AB  - In order to isolate new probes from the juxtacentromeric region of the long arm
      of the human X chromosome, we used Alu-mediated polymerase chain reaction (Alu
      PCR) products as probes to directly screen a chromosome X-specific gridded cosmid
      library. These Alu-PCR products were synthesized from radiation hybrids
      containing the loci DXS159, PGK1, and PGK1P1. This approach allowed us to select
      18 cosmids capable of hybridizing with at least two Alu-PCR products. Four
      cosmids hybridized to more than three Alu-PCR products. Three of these four
      cosmids were contiguous, and the fourth was independent. Two cosmids that
      hybridized with two Alu-PCR products were further characterized. Physical mapping
      indicated that all of these clones are located in the expected region on Xq,
      confirming the validity of our approach.

PMID- 1395716
TI  - Localisation of the gene for human aromatic L-amino acid decarboxylase (DDC) to
      chromosome 7p13-->p11 by in situ hybridisation.
AB  - The human gene for aromatic L-amino acid decarboxylase (DDC) was previously
      assigned to chromosome 7 by analysis of a panel of somatic cell hybrids. We
      report here refinement of this localisation, by in situ hybridisation, to 7p13-
      >p11.

PMID- 1395717
TI  - Regional localization of the selenocysteine tRNA gene (TRSP) on human chromosome
      19.
AB  - The human selenocysteine tRNA gene (TRSP) has been localized on chromosome
      19q13.2-->q13.3 by in situ hybridization and ordered with respect to other genes
      and anonymous DNA markers in this region by linkage analysis in the forty CEPH
      pedigrees. These loci span only 10 cM in males and about 30 cM in females. The
      order of the loci is cen ... D19S7-D19S9-D19S47-CYP2A-CYP2F1-APOC2++ +-(TRSP,
      CKM). CYP2B flanks the CYP2A and CYP2F1 loci, but it cannot be determined whether
      it is proximal or distal to the other two cytochrome P450 loci with respect to
      the centromere.

PMID- 1395718
TI  - Localization of the human urate oxidase gene (UOX) to 1p22.
AB  - The human urate oxidase (E.C.1.7.3.3) gene, UOX, is assigned to chromosome 1 by
      Southern analysis of human x hamster cell hybrids. Using fluorescent in situ
      hybridization, we have mapped this gene to 1p22.

PMID- 1395719
TI  - Chromosomal localization of the rat Harvey-ras-1 gene (HRAS) by in situ
      hybridization.
AB  - The rat Harvey-ras-1 protooncogene (HRAS) has previously been assigned to rat
      chromosome 1. In this study we further refine its localization to region 1q41-
      >q42 through the use of fluorescent in situ hybridization.

PMID- 1395720
TI  - Chromosomal assignments of genes for rat glutathione S-transferase Ya (GSTA1) and
      Yc subunits (GSTA2).
AB  - Chromosomal assignments of genes for rat glutathione S-transferase Ya (GSTA1) and
      Yc subunits (GSTA2) were performed by Southern blot analyses of somatic cell
      hybrid DNAs.GSTA1 and GSTA2 were assigned to rat chromosomes 8 and 9,
      respectively.

PMID- 1395721
TI  - A chromosome 1-specific DNA library from the domestic pig (Sus scrofa domestica).
AB  - Chromosomes were prepared from lymphocytes of a male domestic pig and flow-sorted
      on a dual-laser FACS. Twenty spots were observed, corresponding to the known pig
      karyotype of 18 pairs of autosomes plus the X and Y. DNA was isolated from 10,000
      copies of the presumed chromosome 1 spot, restricted with Sau3A, ligated into the
      vector pGEM4z, and PCR amplified using universal primers; the products were then
      re-ligated into pUC18. After transformation into Escherichia coli, 210,000
      independent colonies were obtained, 5% of which contained only vector DNA. The
      average insert size of the library was 405 bp. Southern blotting revealed that
      36% of the clones contained single-copy DNA and that the remainder contained
      moderately or highly repetitive DNA. Screening with a (CA)n probe revealed that
      roughly 1% of the clones contained microsatellite sequences. A bulk insert of the
      library was biotinylated by PCR and used as a probe for chromosomal in situ
      suppression hybridization to pig chromosomes, which confirmed that the library is
      specific for chromosome 1. However, sequences from the centromeric and telomeric
      regions seem to be underrepresented in the library.

PMID- 1395722
TI  - New gene assignments to rabbit chromosomes; implications for chromosome
      evolution.
AB  - The genes for SOD1 and SOD2 (superoxide dismutases 1 and 2), RB1
      (retinoblastoma), TYMS (thymidylate synthase), and TK1 (thymidine kinase) were
      mapped by in situ hybridization using biotinylated probes to rabbit chromosomes
      6, 12, 8, 9, and 19, respectively. This confirms their proposed homoeologies with
      human chromosomes 21, 6, 13, 18, and 17, respectively, and provides additional
      information on the modification of these chromosomes during evolution.

PMID- 1395723
TI  - Tandem and centric fusions in the chromosomal evolution of the South American
      phyllotines of the genus Auliscomys (Rodentia, cricetidae).
AB  - The karyotypes of three of the four extant species of the genus Auliscomys (A.
      micropus, living in central [2n = 32, NF = 34] and southern [2n = 34, NF = 36,
      37] Chile; A. sublimis [2n = 28, NF = 32] and A. boliviensis [2n = 22, NF = 32],
      which inhabit the Andean Altiplano) were analyzed. Comparisons of G-, C-, and
      AgNOR-banded karyotypes showed that extensive conservation of entire chromosomes
      and chromosomal regions had occurred during the evolution of this genus, with
      centromeretelomere tandem fusions and centric fusions probably being the most
      frequent chromosome changes. A chromosomal phylogeny, based on the chromosome
      homoeologies detected and parsimonious analysis of the nature and distribution of
      the inferred chromosomal changes, is proposed. This hypothetical phylogeny
      assumes that the ancestral telocentric karyotype would have undergone three
      consecutive tandem fusions, first originating the 2n = 32 (NF = 34) karyomorph
      exhibited by present-day specimens of A. micropus captured in central Chile and
      then the 2n = 28 (NF = 32) karyotype of A. sublimis. Subsequent centric fusions
      involving the tandem-fusion products would presumably have generated the 2n = 22
      (NF = 32) A. boliviensis karyotype. Assuming some conditions related to early
      geographic distribution, this chromosomal phylogeny is in agreement with a
      paleogeographic model, which explains the present distribution of living
      Auliscomys species mainly on the basis of geologic and climatic events.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1395724
TI  - Localisation of the beta crystallin Cryb gene to mouse Chromosome 2B-->C1 by in
      situ hybridisation.
AB  - The beta crystallin gene Cryb (betaA3/A1) has been assigned to mouse Chromosome 2
      region B-->Cl by in situ hybridisation to metaphase chromosomes from mouse foetal
      liver and bone marrow preparations of Rb(2.17)4H mice using a murine cDNA
      (pMbeta23Crl) probe.

PMID- 1395725
TI  - Segregation analysis reveals tight genetic linkage between the spontaneously
      arising neural tube defect gene splotch (Sp) and Pax-3 in an intraspecific mouse
      backcross.
AB  - Concurrent research has recently characterized Sp2H, a radiation induced mutation
      at the splotch (Sp) locus, and found alterations in the murine paired box gene,
      Pax-3, in homozygous Sp2H DNA. It was proposed that Sp and Pax-3 are the same
      gene. This report presents additional genetic evidence in support of this finding
      through linkage studies. Southern blot analysis of genomic DNAs from a panel of
      125 intraspecific [(Sp/+ x CBA/J)F1-Sp x CBA/J] backcross mice reveals no
      crossover between Pax-3 and the spontaneously occurring splotch allele, Sp. This
      positions Pax-3 within 2.9 cM of the Sp locus (95% confidence interval) and
      suggests tight genetic linkage between the two marker genes.

PMID- 1395726
TI  - The gene map of the pig (Sus scrofa domestica L.): a review.
AB  - A review of the present status of the porcine gene map is given with references.
      A total of 84 loci have now been studied, and genes have been assigned to 17
      chromosomes. Among them, six chromosomes are defined by only one marker. No loci
      have been attributed yet to three chromosomes.

PMID- 1395727
TI  - Assignment of a porcine male-specific DNA repeat to Y-chromosomal
      heterochromatin.
AB  - Primers were designed to amplify by PCR a 509-bp genomic fragment from male pig
      DNA, using the porcine male-specific repeat sequence described by McGraw et al.
      (1988). This PCR product showed male-specific hybridization in Southern blots.
      Nonradioactive in situ hybridization localized it to the entire length of the
      heterochromatic portion of Yq. The assignment was confirmed using the PCR primer
      pDYZ1-S for primed in situ labeling.

PMID- 1395728
TI  - Microchromosomal assignment of the chicken ovotransferrin and adenylate kinase
      genes.
AB  - Ovotransferrin, an egg-white protein implicated in the transfer of trace elements
      from the hen oviduct to the developing avian embryo, and cytosolic adenylate
      kinase, an essential enzyme involved in the interconversion of adenine
      nucleotides in energetically active tissues, have been mapped to two separate
      chicken microchromosomes by fluorescent in situ hybridization. Considering
      present and previous data, the possibility of loss of intron material resulting
      in the compactation of genes in chicken microchromosomes is briefly discussed.

PMID- 1395730
TI  - A satellite III sequence shared by human chromosomes 13, 14, and 21 that is
      contiguous with alpha satellite DNA.
AB  - We report the isolation of a clone (pTR9) from a human chromosome 21 lambda phage
      library, which was found to contain two distinct components: (1) a previously
      unreported subfamily of human satellite III (pTR9-s3; 1,485 bp) and (2) an alpha
      satellite sequence (pTR9-alpha; 250 bp) containing 1.5 copies of a 171-bp alphoid
      unit that shows 88.4% homology to a previously reported alpha satellite consensus
      sequence. The two components are separated by two direct repeats of 9 bp. Use of
      the polymerase chain reaction (PCR) to amplify across the junction between pTR9
      s3 and pTR9-alpha established that these two sequences are contiguous in total
      human genomic DNA and in DNA derived from somatic cell hybrids carrying human
      chromosomes 13, 14, or 21. A related, but considerably more diverged, sequence
      was also detected on chromosome 15. Southern analysis of somatic cell hybrids at
      high stringency revealed a common structure of the pTR9-s3 sequence on
      chromosomes 13, 14, and 21 but not on 15 or 22. This sequence should be useful
      for the study of the structural organisation of the centromere of these
      chromosomes and the mechanism of their involvement in Robertsonian
      translocations.

PMID- 1395729
TI  - The genes for protamine 1 and 2 (PRM1 and PRM2) and transition protein 2 (TNP2)
      are closely linked in the mammalian genome.
AB  - The genes for two protamines (PRM1 and PRM2) and for two transition proteins
      (TNP1 and TNP2) have been characterized in several mammalian species. In the
      human, boar, and bull, the genes for PRM1, PRM2, and TNP2 are closely linked over
      a stretch of DNA 13-15 kb long. Although similar data are not yet available for
      the mouse and rat, our results suggest that the three genes are similarly linked
      in these species. The gene for TNP1 in all species studied is located on another
      chromosome.

PMID- 1395731
TI  - Molecular characterization of a mouse Y chromosomal repetitive sequence that
      detects transcripts in the testis.
AB  - 145SC5 is a Y chromosomal repetitive sequence isolated from a BALB/c mouse and is
      unique in that it detects poly(A)-containing transcripts in the testis. We
      determined nucleotide sequences of 145SC5 and a related cDNA clone designated
      PC11 and compared their sequences to that of pYMT2/B, another related cDNA clone.
      145SC5 and PC11 are almost identical (97%), while PC11 and pYMT2/B share 84%
      identity. In situ hybridization and Southern blot analysis with XXSxr male mice
      demonstrated that 145SC5-related sequences were distributed over the entire
      length of the Y chromosome including the short arm. Two types of Y chromosome are
      present in inbred mouse strains: the Mus musculus musculus type and M.m.
      domesticus type. Among 26 inbred strains surveyed, 145SC5 detected polymorphims
      only in the M.m. domesticus Y chromosome.

PMID- 1395732
TI  - Detection of cell-cycle stage by fluorescence in situ hybridization: its
      application in human interphase cytogenetics.
AB  - Distinct cell-cycle-dependent changes in the conformation of centromeric
      chromatin in a specific human chromosome containing alpha-satellite DNA have been
      demonstrated by fluorescence in situ hybridization (FISH). This method, based
      upon specific FISH signal morphology, allows simultaneous analysis of chromosomal
      aneuploidy and detection of specific cell-cycle stage(s) of human tumor and/or
      normal cell populations in a single preparation of interphase cells. This
      interphase cytogenetic procedure might prove useful for both basic and clinical
      research involving human cells.

PMID- 1395733
TI  - Sister chromatid differentiation and chromosomal in situ suppression
      hybridization: a combined methodology for analyzing cell proliferation and SCEs
      in individual chromosomes.
AB  - A technique combining sister chromatid differentiation (SCD) with chromosomal in
      situ suppression (CISS) hybridization is described. This combined methodology
      allows simultaneous analysis of cell-proliferation kinetics and sister chromatid
      exchanges (SCEs) in chromosomes identified by probes. To demonstrate the
      usefulness of this approach, cultured fibroblasts from a patient with Pallister
      Killian syndrome, mos46/47,+i(12p), a chromosome mosaicism disorder, were
      studied. The fibroblasts were cultured in the presence of 5-bromodeoxyuridine
      (BrdU) for 72 h. Chromosome preparations were stained by a modified fluorescence
      plus-Giemsa method to obtain SCD. For identification of the normal chromosome 12
      and the i(12p), CISS hybridization with a biotin-labeled chromosome 12-specific
      library probe (LA 12NS01) was carried out after SCD. The hybridization was
      detected by an indirect immunofluorescence technique. For the analysis of cell
      kinetics and SCEs, the technique allows rapid, reliable identification of
      abnormal and normal cell populations. It also allows analysis of SCEs in
      individual chromosomes.

PMID- 1395734
TI  - Amiodarone pneumonitis. Bronchoalveolar lavage findings in 15 patients and review
      of the literature.
AB  - Amiodarone (Am) pneumonitis is currently a common and potentially severe adverse
      reaction, the accurate diagnosis of which remains difficult to establish.
      OBJECTIVES: To determine the contribution of bronchoalveolar lavage (BAL) in the
      diagnostic workup of patients suspected of having Am pneumonitis. METHODS:
      Diagnosis of Am pneumonitis was established on the basis of (1) development of
      recent symptoms and pulmonary opacities while receiving the drug, (2) exclusion
      of other possible causes, and (3) improvement following cessation of Am and/or
      steroid therapy. (4) Confirmatory changes were obtained by histopathologic
      examination in eight cases. BAL was performed in each patient at the time of
      initial evaluation. RESULTS: Am pneumonitis was diagnosed in 15 consecutive
      patients between 1985 and 1991. The disease was associated with significant
      morbidity and mortality. Six patients died; four died of Am pneumonitis. A
      neutrophilic BAL was found in nine patients (average PMN = 26.6 percent). A mixed
      pattern (lymphocytic + neutrophilic) was seen in four patients (average: Ly =
      19.9 percent; PMN = 11.9 percent). Two patients had a normal BAL. No patient had
      a lymphocytic pattern. A low CD4+/CD8+ ratio was seen in two patients. A
      literature survey indicated 70 cases of Am pneumonitis with detailed information
      on BAL. The BAL pattern was mixed in 23 (33 percent), neutrophilic in 18 (26
      percent), lymphocytic in 15 (21 percent), and normal in 14 (20 percent). No
      correlation was found between BAL pattern and prognosis. Also, BAL pattern was
      related neither to daily or total dose of Am nor to duration of treatment with
      Am. CONCLUSION: The cellular profile of BAL in Am pneumonitis is highly variable,
      and no cellular pattern of BAL seems to be predictive of a detrimental outcome or
      of irreversible fibrosis. Aside from excluding other illnesses, and due to its
      extreme variability, the contribution of BAL differential in the initial workup
      of patients suspected of having Am pneumonitis is limited.

PMID- 1395735
TI  - Does achalasia predispose to cancer of the esophagus?
AB  - In a follow-up study of 147 patients with achalasia of the esophagus treated by
      myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83
      years [median, 46 years]). The living persons were contacted in writing or by
      telephone. The mean follow-up time after the operation was 23.2 years (range, 6
      to 41 years). The cause of death was established for 71 patients. There were
      three postoperative deaths and two deaths following recurrence. In comparison
      with the Danish population, the 66 remaining patients were found to have a
      relatively higher cancer mortality (33.8 percent). Contrary to the expected less
      than one, ten of 23 patients who died of cancer had a malignant tumor in the
      esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of
      the deaths caused by esophageal cancer. It is concluded that there is a
      connection between achalasia and cancer of the esophagus that ought to be
      considered in the treatment and follow-up of patients with achalasia.

PMID- 1395736
TI  - Improved ventilatory response to exercise after cardioversion of chronic atrial
      fibrillation to sinus rhythm.
AB  - The purpose of this study was to assess hemodynamic and respiratory measures of
      submaximal and maximal exercise performance in patients with chronic atrial
      fibrillation, before and one month after cardioversion to sinus rhythm.
      Restoration of sinus rhythm (n = 16) produced significant reductions in resting
      and exercise heart rates, 14 percent to 20 percent (p < 0.01). Due to a
      proportionately larger increase in stroke volume, cardiac output increased by 9
      percent during low-level exercise (p < 0.01) and by 7 percent during exercise
      above the anaerobic threshold (p < 0.05). Minute ventilation was reduced by 7
      percent during low-level exercise (p < 0.01) and by 9 percent above the anaerobic
      threshold (p < 0.05). The ratio between minute ventilation and carbon dioxide
      elimination was significantly reduced (p < 0.01). Maximum oxygen uptake (+8
      percent; p < 0.01) and maximal tolerated work load (+6 percent; p < 0.05)
      increased. Hemodynamic changes during exercise were similar in patients with (n =
      7) or without (n = 9) disopyramide prophylaxis. Restoration of sinus rhythm
      induced improvement in hemodynamics and in efficiency of ventilation, thereby
      reducing the ventilatory demand during submaximal exercise.

PMID- 1395737
TI  - Heart rate variability during sleep in snorers with and without obstructive sleep
      apnea.
AB  - Changes in sympathetic and vagal tone may be the substrate for the development of
      cardiac arrhythmias in patients with obstructive sleep apnea (OSA). The
      cardiovascular responses in the traditional autonomic tests show great
      interindividual and intraindividual variations. During sleep there are repetitive
      modifications of heart rate (HR) that are not influenced by psychologic factors
      or the patient's cooperation. For this reason, we evaluated HR modifications in
      relation to spontaneous body movements (BM) and sleep apneas during nonrapid eye
      movement (NREM) and rapid eye movement (REM) sleep in habitual snorers with
      normal and pathologic respiratory disturbance index (RDI). From 132 consecutive
      patients referred to our sleep center for habitual snoring and/or daytime
      somnolence, we selected 35 male patients younger than 60 years without clinical
      evidence of autonomic dysfunction. They were divided into three groups: group A
      (RDI < 10); group B (RDI > 10 and < 20); and group C (RDI > 20). No significant
      difference was found among the three groups in the HR variability related to BM.
      In the evaluation of bradytachyarrhythmias related to apneic events of 20 to 30
      s, we found a significant difference between group A and the other two groups. In
      patients with RDI > 10, a reduced HR variability related to a reduced sympathetic
      tone in the post-apnea phase was observed. Some authors suggested that an HR
      increase during the post-apnea period can be used as an index of "brainstem
      arousal." Our results seem to indicate a reduced apnea-related "arousability" in
      patients with RDI > 10. This finding might be one of the factors contributing to
      the worsening of OSA.

PMID- 1395739
TI  - Changes in hospital admissions pattern in patients with human immunodeficiency
      virus infection in the era of Pneumocystis carinii prophylaxis.
AB  - BACKGROUND: Pneumocystis carinii pneumonia (PCP) was the leading cause of
      hospital admissions in patients with human immunodeficiency virus (HIV) infection
      before the widespread use of PCP prophylaxis. We studied retrospectively the
      changes in annual hospital admission patterns after the start of a population
      based PCP prophylaxis program in Toronto. The purpose of the study was to
      identify the cogent diseases requiring hospitalization of HIV patients in the
      current era of PCP prophylaxis. This information is important for the allocation
      of health care resources in the future as well as for targeting research in the
      prevention of specific HIV-related diseases. METHODS: The annual HIV-related
      hospital admissions before and after the start of the Toronto aerosol pentamidine
      program (May 1989) were studied. All admission records due to AIDS-defining
      illnesses or occurring in patients with known HIV status in three major referral
      centers were reviewed. The two periods for comparison were May 1988 through April
      1989 and May 1989 through April 1990. The data obtained were stratified according
      to the following: (1) cause of the illness prompting hospital admission; (2) PCP
      admissions; and (3) admissions according to the major organ system involved.
      These categoric data were compared by nonparametric chi 2 tests. RESULTS AND
      CONCLUSIONS: Population-based prophylaxis of PCP with aerosol pentamidine
      resulted in a significant reduction in the total number of PCP hospital
      admissions. Infection remains the principal cause of hospital admission in HIV
      patients after the start of the PCP prophylaxis program. However, there was an
      increase in the proportion of hospital admissions due to nonrespiratory-related
      infections. There was also a modest increase in admissions due to neurologic and
      gastrointestinal diseases. Central nervous system lymphoma and cytomegalovirus
      retinitis accounted for the majority of the rise in the nervous system. These
      data suggest there is a changing pattern of the diseases leading to the
      hospitalization of patients with HIV infection in the era of PCP prophylaxis.

PMID- 1395738
TI  - Noninvasive determinations of the anaerobic threshold. Reliability and validity
      in patients with COPD.
AB  - We compared the intraobserver and interobserver agreement of blood (BGT) and gas
      exchange (GET) methods for determination of the anaerobic threshold (AT) in
      patients with COPD. In addition, we determined the sensitivity and specificity of
      the gas exchange methods for determination of the AT. Two noninvasive methods,
      the V-slope (VS) and the ventilatory equivalents method (VEM) were compared with
      two blood sampling methods, the log standard HCO3 (SB) vs log VO2 (SBT) and base
      excess (BE) vs VO2 (BET). Twenty-nine patients with COPD (FEV1 < 60%) performed
      incremental exercise tests to exhaustion while breath-by-breath gas exchange
      measurements were made. Blood samples were drawn at the end of each minute for SB
      and BE. Two trained observers determined the VO2 at the threshold for each of the
      four indices on two separate occasions two weeks apart. Our results demonstrated
      the following: only modest interobserver and intraobserver agreement was noted by
      Spearman rank correlations; the VEM was as sensitive as the VS in COPD patients;
      and the presence of a true metabolic acidosis was not reliably predicted by GET
      methods. Moreover, although the blood methods accurately identified the presence
      of metabolic acidosis, there was disagreement on the actual point of the BGT. We
      conclude that gas exchange indices were not helpful for the determination of
      metabolic acidosis in patients with COPD.

PMID- 1395740
TI  - Yield of bronchoscopy for the diagnosis of tuberculosis in patients with human
      immunodeficiency virus infection.
AB  - The efficacy of bronchoscopy for the diagnosis of tuberculosis in patients
      infected with human immunodeficiency virus (HIV) has not been systematically
      evaluated. We therefore compared the diagnostic yield of bronchoscopy in 67 HIV
      infected and 45 non-HIV-infected patients with culture-proven pulmonary
      tuberculosis. In all cases, acid-fast smears of sputum were negative or not
      obtained prior to bronchoscopy. Prebronchoscopic sputum culture yielded
      Mycobacterium tuberculosis in 34 (89 percent) of 38 HIV-infected patients and 26
      (93 percent) of 28 non-HIV-infected patients from whom specimens were obtained.
      Bronchoscopy provided an early diagnosis of tuberculosis (positive acid-fast
      smear or granulomata on biopsy) in 23 (34 percent) of the HIV-infected patients
      and 20 (44 percent) of the patients without HIV infection. The sensitivities of
      the acid-fast smear and of mycobacterial culture of bronchoscopic specimens and
      postbronchoscopic sputum were similar in patients with or without HIV infection.
      In HIV-infected patients, granulomatous inflammation was noted on transbronchial
      biopsy in 11 (19 percent) of 59 patients with HIV infection, compared to 16 (43
      percent) of 37 patients without HIV infection (p = 0.01). Nevertheless,
      transbronchial biopsy provided the exclusive means for an early diagnosis of
      tuberculosis in six (10 percent) of 59 HIV-infected patients. We conclude that
      the yield of bronchoscopy for the diagnosis of pulmonary tuberculosis in HIV
      infected patients is similar to that in patients without HIV infection, and that
      transbronchial biopsy provides incremental diagnostic information not available
      from evaluation of sputum or bronchoalveolar lavage fluid.

PMID- 1395741
TI  - Prospective evaluation of a prognostic score for Pneumocystis carinii pneumonia
      in HIV-infected patients.
AB  - Serum lactate dehydrogenase levels, alveolar-arterial oxygen gradient, and
      percentage of neutrophils in bronchoalveolar lavage correlate most strongly with
      early mortality in Pneumocystis carinii pneumonia (PCP) in HIV-infected patients.
      However, the individual outcome can not be predicted by these parameters due to a
      considerable overlap between survivors and nonsurvivors. We prospectively
      investigated a PCP severity score, which has been developed earlier based on a
      retrospective analysis. Seven of 94 consecutively examined HIV-infected patients
      died within 14 days after diagnosis of PCP. A PCP severity score greater than 7
      had a positive predictive value for early fatal outcome of 66.7 percent (6/9) and
      a negative predictive value of 98.8 percent (84/85). The overall diagnostic
      accuracy was 95.7 percent (90/94). The positive predictive value for early fatal
      outcome of a P(A-a)O2 > 35 mm Hg was 24 percent (6/25); the negative predictive
      value was 98.6 percent (68/69). However, the overall diagnostic accuracy was only
      78.7 percent (74/94). The PCP severity score is a valuable tool for clinical
      decision making, for the early identification of patients with a prognostic
      unfavorable course, and for the comparison of patient populations in future
      studies of HIV-associated PCP.

PMID- 1395742
TI  - Interleukin 6 activity in pleural effusion. Its diagnostic value and
      thrombopoietic activity.
AB  - We measured interleukin 6 (IL-6) concentrations in the pleural fluid of various
      patients to determine its role in pathophysiology and diagnosis by using specific
      functional bioassay. IL-6 levels were significantly higher in exudate than in
      transudate (79.3 +/- 176.2 U/ml [n = 55] vs 1.7 +/- 1.8 U/ml [n = 12]; p < 0.01).
      Tuberculous effusion contained a significantly higher amount of IL-6 than
      malignant effusion (181.3 +/- 176.2 U/ml [n = 13] vs 29.4 +/- 71.5 U/ml [n = 29];
      p < 0.005). Pleural IL-6 levels were invariably higher than serum IL-6 levels,
      and both were significantly correlated (n = 21, r = 0.632; p < 0.02). Pleural IL
      6 levels were significantly correlated with lactate dehydrogenase (LDH) in
      pleural fluid (r = 0.392; p < 0.01), ratio of pleural/serum LDH (r = 0.571; p <
      0.01), pleural adenosine deaminase activity (r = 0.599; p < 0.01), and serum C
      reactive protein (r = 0.494; p < 0.01). Furthermore, IL-6 levels were
      significantly correlated with peripheral blood platelet counts (r = 0.447; p <
      0.001). These results suggest that (1) IL-6 is produced locally in pleural space,
      (2) pleural IL-6 level is helpful for differential diagnosis, and (3) locally
      produced IL-6 could leak to circulation and cause systemic effects such as the
      induction of C-reactive protein and thrombocytosis.

PMID- 1395743
TI  - Pleural SC5b-9 in differential diagnosis of tuberculous, malignant, and other
      effusions.
AB  - A monoclonal antibody against soluble phase-terminal complement complex (SC5b-9)
      was used to try to differentiate pleural effusions of tuberculous vs malignant
      and other origin. Effusions of tuberculous origin showed a significantly higher
      SC5b-9 level than did plasma, suggesting activation of complement in the pleural
      space. All 26 patients with tuberculous effusions showed SC5b-9 levels in pleural
      fluid exceeding 2.0 mg/L, while 20 with malignant effusions had levels less than
      2.0 mg/L. However, rheumatoid, some parapneumonic, and treated malignant
      effusions showed SC5b-9 levels above 2.0 mg/L. Considering a value exceeding 2.0
      mg/L, the specificity and sensitivity of the SC5b-9 estimation in tuberculosis
      were 0.74 and 1.0, respectively. The mean values for C4d and Bb fragments of
      complement were significantly (p < 0.05) higher in the tuberculous than in the
      malignant effusions. However, the values for Bb in 16 (62 percent) of the 26
      patients with tuberculous or malignant effusions were in the same range. The
      activity of adenosine deaminase (ADA) was higher in the tuberculous than in the
      malignant effusions. While 18 of 26 patients with tuberculous effusions showed an
      ADA value exceeding 50 mU/ml, the estimated cutoff point (sensitivity = 0.69), 35
      of the 36 nontuberculous effusions showed a true negative value (specificity =
      0.97). A correlation between ADA and SC5b-9 values was observed in pleural
      effusions. These observations suggest that the estimation of SC5b-9 in pleural
      fluid presents a new approach to differentiating tuberculous vs malignant
      effusions.

PMID- 1395744
TI  - From apnea of infancy to obstructive sleep apnea syndrome in the young child.
AB  - Obstructive sleep apnea syndrome (OSAS) and heavy snoring during sleep, without
      sleep apnea, has been well described in children and adults. We report a case
      series of 25 full-term infants, prospectively obtained from a database of nearly
      700 "apparent life-threatening event" (ALTE) cases, who presented between 3 weeks
      and 4 1/2 months of age an ALTE and who progressively developed more florid
      symptomatology and polygraphic findings. All of them were classified as OSAS
      patients by five years of age. These index cases are compared with two other ALTE
      infant groups followed in parallel during the first year of life but whose
      symptoms were short-lived. The index cases presented more frequently a positive
      family history of OSAS and an early report of snoring or noisy breathing during
      sleep. Usage of an esophageal balloon to monitor esophageal pressure (Pes) and
      usage of nasal continuous positive airway pressure (CPAP) as a test may help in
      the early recognition of these infants, who appear to make more effort to breathe
      during sleep, based on the indirect evidence of Pes measurements. It is suggested
      that anatomic features, including a small posterior airway space leading to an
      abnormal degree of upper airway resistance, may be the cause of the symptoms
      presented by these infants. Considering the parental anxiety generated by
      persistence of symptoms after the first year of life in ALTE infants, recognition
      of this subgroup is important.

PMID- 1395745
TI  - Endobronchial irradiation with 192Ir in the treatment of malignant endobronchial
      obstruction.
AB  - From Jan 1, 1983 to April 30, 1989, 32 patients underwent 38 endobronchial
      treatments with 192Ir, bronchoscopically inserted for treatment of endobronchial
      obstructions secondary to bronchogenic carcinoma. Thirty-four of the 38
      treatments were far enough apart to allow separate response analysis. Thirty of
      the 34 patients were symptomatically improved or stable; 22 of 24 patients who
      could be evaluated roentgenographically showed improved or stable chest
      roentgenograms, and ten of 12 patients evaluated bronchoscopically demonstrated
      improved patency of bronchial lumen.

PMID- 1395746
TI  - Extended monitoring of oxygen saturation in chronic lung disease.
AB  - The goal was to determine values of oxygen saturation from oximetry measurements
      over extended time periods in the context of prescribing or discontinuing
      supplemental oxygen. For group 1, when supplemental oxygen therapy was not in
      use, mean SpO2 values were significantly lower than when it was in use. Without
      supplemental oxygen, six of eight patients spent greater than 10 percent of the
      time at or below 88 percent saturation. For group 2, three of the nine patients
      spent 10 percent of the time at or below 88 percent SpO2. In 16 of 17 patients,
      lowest room air recorded values of SpO2 were less than 88 percent. We conclude
      that in many patients with chronic respiratory illness, prolonged monitoring of
      SpO2 will disclose the presence of hypoxemia. There may be substantial
      differences in health care cost and outcome depending upon the criteria chosen to
      prescribe or continue supplemental oxygen.

PMID- 1395747
TI  - Utility of repeated fiberoptic bronchoscopy for suspected malignancy.
AB  - We retrospectively evaluated records of 1598 fiberoptic bronchoscopies (FBs)
      performed on 1,391 patients (PTs) between Jan 1, 1986 and Dec 31, 1990. We found
      a progressive increase from 11 percent to 20 percent in the use of repeated
      fiberoptic bronchoscopy (RFB). Of the 254 RFBs, 151 were done in PTs with known
      or suspected intrathoracic malignant neoplasms. The 78 (of 151) RFBs performed in
      PTs with previously diagnosed malignant neoplasms were used to guide additional
      therapy. The other major indication for RFB (67 of 151) was to evaluate new
      suspicious lesions that had not been diagnosed on the initial FB. RFB specimens
      were positive in 36, false-negative in 24, and true-negative in 7 PTs. For some
      PTs, RFB could probably have been avoided if at initial FB physicians had (1)
      used fluoroscopy to direct transbronchial lung biopsies in PTs expected to have
      normal airways, (2) performed transbronchial needle aspiration in all PTs with
      extraluminal disease or mediastinal adenopathy, and (3) obtained bronchial biopsy
      specimens from all PTs with endobronchial lesions. In PTs whose initial FB
      specimens were nondiagnostic despite visualization of endobronchial or
      extraluminal abnormalities, RFB was associated with a significant diagnostic
      yield and obviated the need for more morbid, surgical staging procedures.

PMID- 1395748
TI  - Production of collagenase and tissue inhibitor of metalloproteinases by
      fibroblasts derived from normal and fibrotic human lungs.
AB  - Several experiments have demonstrated low collagenolytic activity during the
      development of pulmonary fibrosis. In order to determine if fibroblasts play a
      role in this alteration, procollagenase and tissue inhibitor of
      metalloproteinases (TIMP) were quantified in fibroblasts derived from 12 human
      lung specimens (normal = 6, idiopathic pulmonary fibrosis [IPF] = 6). Under basal
      conditions, three cell strains from normal and three from fibrotic lung specimens
      did not synthesize collagenase and a similar number of normal and IPF-derived
      fibroblast strains produced the enzyme. However, the rate of enzyme synthesis
      among normal and fibrotic collagenase producing fibroblasts exhibited significant
      differences. Thus, whereas normal fibroblasts produced more than 300 ng/ml,
      fibrotic lung fibroblasts secreted approximately half of this amount (115 +/- 67
      ng/ml). Phorbol myristate acetate (PMA) enhanced collagenase production in all of
      the 12 lung fibroblast lines tested. In four IPF fibroblasts, PMA increased
      collagenase secretion close to those of normal stimulated lung fibroblasts;
      however, a lower induction was observed in cell strains from two fibrotic lung
      specimens. There was a wide variation in TIMP production both in normal and
      fibrotic lung fibroblasts, and no statistically significant difference was
      observed. Under basal conditions, TIMP levels ranged from 329 to 16,911 ng/ml in
      normal lung cells, and from 377 to 17,557 in fibrotic lung fibroblasts. PMA
      induced a severalfold increase in all cell lines. These results suggest that
      there are subpopulations of lung fibroblasts with different potential to produce
      collagenase and TIMP in vitro, and that the predominance of low collagenase
      producing subsets may contribute to the development of fibrosis.

PMID- 1395749
TI  - Use of intermittent, intravenous cyclophosphamide for idiopathic pulmonary
      fibrosis.
AB  - STUDY OBJECTIVE: To determine the safety and efficacy of intravenous
      cyclophosphamide for patients with idiopathic pulmonary fibrosis. DESIGN:
      Nonrandomized, open-labeled study of efficacy in symptomatic patients. SETTING:
      Patients were treated as outpatients in a referral clinic. PATIENTS: All patients
      had idiopathic pulmonary fibrosis with symptoms of dyspnea on exertion. Patients
      had either worsening disease or contraindication to corticosteroids.
      INTERVENTION: Thirty-three patients were treated with intravenous
      cyclophosphamide every two weeks. Initial dosage was 500 mg, and the dose was
      escalated provided the total white blood cell count remained > 3,000 cells per
      cubic millimeter. The maximum dose administered was 1,000 to 1,800 mg of
      cyclophosphamide. Corticosteroid therapy was tapered as tolerated by the patient.
      MEASUREMENTS AND RESULTS: Patients were treated for at least six months or until
      death. For the 33 patients, 18-month probability of survival was > 50 percent.
      For those patients surviving six months, there was a significant rise in the
      vital capacity (from 1.6 +/- .61 L [mean +/- SD] to 1.8 +/- .52 L, p < 0.01)
      which persisted for at least 18 months of treatment. This was associated with a
      significant fall in the average prednisone dosage from 32 +/- 13.0 mg/day to 4 +/
      10.4 mg/day (p < 0.01) by 12 months. Only one patient required hospitalization
      for possible drug-related toxic reaction. CONCLUSIONS: Intermittent, intravenous
      cyclophosphamide therapy was associated with improved pulmonary function and
      reduced corticosteroid dosage in patients with idiopathic pulmonary fibrosis who
      survived at least six months after institution of therapy.

PMID- 1395750
TI  - Reduction of alveolar-capillary diffusion after inhalation of endotoxin in normal
      subjects.
AB  - Normal subjects were exposed to an aerosol of Escherichia coli endotoxin. Carbon
      monoxide diffusion (Dco), spirometry, blood neutrophils, white blood cells, and
      platelets were determined at various times thereafter. A significant decrease in
      Dco and an increase in blood neutrophils was found, with a maximum effect 4 to 8
      h after exposure. Exposure to distilled water caused a tendency for Dco to
      decrease and a significant increase in blood neutrophils. No effect on spirometry
      or body temperature was detected. It is suggested that the changes observed
      represent an inflammation at the alveolar level that appears at dose levels of
      endotoxin below those which cause bronchoconstriction and fever.

PMID- 1395751
TI  - Metabolic effects of inhaled fenoterol in normal subjects.
AB  - Although the hypokalemic effect of inhaled beta 2-adrenergic agonists has been
      well documented, little is known as to their effect on plasma magnesium. We
      therefore examined in ten healthy young volunteers the effect of the inhalation
      of 2 mg of nebulized fenoterol on plasma potassium (Kpl), plasma magnesium
      (Mgpl), and intraerythrocytic magnesium (MgIE) levels, as well as on plasma
      insulin and C peptide concentrations, measured before and serially up to 110 min
      after fenoterol inhalation. In all subjects, fenoterol inhalation caused a
      reversible reduction in Kpl (range, 0.2 to 1.1 mEq/L), which was progressive,
      reaching a statistically significant nadir 30 to 60 min following fenoterol
      inhalation (largest dip in Kpl, 0.55 +/- 0.29 mEq/L; p < 0.05). The nadir in Kpl
      levels was preceded by a peak in plasma insulin levels in all subjects. No
      significant changes in Mgpl or MgIE were observed in any of the subjects. We
      conclude that fenoterol inhaled at a dosage used in clinical practice
      significantly reduces Kpl but not Mgpl nor MgIE levels in healthy subjects,
      indicating a lower sensitivity of Mg++ ions to beta 2-adrenergic stimulation than
      K+ ions. Beta 2-adrenergic-induced insulin secretion probably contributes to the
      hypokalemic effect of inhaled fenoterol.

PMID- 1395752
TI  - Is asymptomatic bronchial hyperresponsiveness an indication of potential asthma?
      A two-year follow-up of young students with bronchial hyperresponsiveness.
AB  - To determine the possibility that asymptomatic bronchial hyperresponsiveness
      (BHR) develops into symptomatic asthma, a two-year follow-up study was conducted
      in 81 students (48 male, 33 female; 11 to 17 years) who were found to have BHR in
      a 3,067 population survey (BHR group). Eighty-eight age-matched students (48
      male, 40 female) with normal bronchial responsiveness served as control subjects.
      Daily symptom cards were recorded. Peak expiratory flow rate was measured for 24
      h when symptoms occurred. Histamine inhalation tests were performed at the
      beginning of the study and at the end of the first and the second year. In the
      BHR group, 58 students remained bronchial hyperresponsive at the end of follow
      up. Nine of 31 students with initially diagnosed bronchial asthma had their
      symptoms relieved entirely, but ten asymptomatic students developed asthma. The
      incidence of newly diagnosed asthma (12.5 percent in the BHR group or 20 percent
      in the asymptomatic BHR group) and the total percentage of diagnosed asthma (39.5
      percent) in the BHR group were significantly higher than those (2.27 percent,
      2.27 percent) in the control group. FVC and FEV1 showed no significant difference
      between two groups. PD20 FEV1 values in newly diagnosed asthmatics were
      significantly lower than those in asymptomatic students both at the beginning
      (3.05 +/- 1.56 mumol vs 6.14 +/- 1.60 mumol, p < 0.05) or the end (3.47 +/- 1.73
      mumol vs 6.55 +/- 1.51 mumol, p < 0.05). The percentage of early respiratory
      illness was significantly higher in those with newly diagnosed asthma (80
      percent) than in asymptomatic students (22.3 percent), but atopic index and the
      percentage of parental asthma showed no difference between two groups. In nine
      asthmatics whose symptoms were relieved entirely in the two-year follow-up, PD20
      FEV1 was undetectable within the cumulative dose of 7.8 mumol of histamine in
      three students and rose from 4.58 +/- 1.85 mumol to 7.62 +/- 1.02 mumol in the
      remaining six. The higher the BHR, the more likely the students developed asthma.
      About 45 percent of asymptomatic students with PD20 < or = 3.2 mumol developed
      asthma in the following two years and 80 percent of them had a history of early
      respiratory illness, suggesting that they may have subclinical or potential
      asthma.

PMID- 1395753
TI  - The role of closed pleural needle biopsy in the diagnosis of malignant
      mesothelioma of the pleura.
AB  - Malignant mesothelioma of the pleura is a disease that requires a biopsy
      procedure for a definitive diagnosis. In the past, closed pleural needle biopsy
      (CPNB) has given poor yields due to the small amount of tissue obtained, and the
      patient has subsequently been subjected to a diagnostic thoracotomy. In recent
      years, the availability of more accurate histopathologic tests have enabled the
      pathologist to make a diagnosis more easily on samples obtained at CPNB. In this
      retrospective study of 20 consecutive cases of malignant mesothelioma of the
      pleura diagnosed between 1980 and 1990, we found that a blind CPNB was diagnostic
      in five of seven procedures and CT-guided CPNB was diagnostic in five of six
      procedures. An open pleural biopsy (OPB) was diagnostic in ten of ten procedures
      performed. There were no complications associated with any of the CPNB
      procedures. We conclude that CPNB is a safe and effective manner of diagnosing
      malignant mesothelioma of the pleura, and should be attempted prior to OPB.

PMID- 1395754
TI  - Cardiac output determination during progressive exercise in cystic fibrosis.
AB  - Cardiac output (Q) determination using the equilibrium CO2-rebreathe indirect
      Fick technique (Equil) to estimate mixed venous PCO2 (Pv-CO2) has been validated
      during steady state (SS) exercise in subjects with lung disease. A modification
      of the exponential method using a low concentration of CO2 with an exponential
      rise in PEt-CO2 (Ex) during rebreathing to estimate Pv-CO2 has been validated
      during nonsteady state exercise. The purpose of the present study was to validate
      the Ex method in subjects with lung disease. Q was measured by Ex at every second
      work load during Prog. Q was measured after 5 min of SS exercise by both Ex and
      Equil. Arterial PCO2 was estimated from PEtCO2. There was no significant
      difference in the Q-VO2 relationship during Prog exercise between the combined
      control and mild (FEV1 > 70%) CF subjects or the moderate and severe CF subjects.
      Q can be determined in the nonsteady state using the exponential CO2-rebreathe
      indirect Fick technique in subjects with CF, allowing for noninvasive examination
      of cardiopulmonary interaction during exercise at a wide range of work loads.

PMID- 1395755
TI  - Fick-derived hemodynamics. Oxygen consumption measured directly vs oxygen
      consumption calculated from CO2 production under steady state and dynamic
      conditions.
AB  - Indirect calorimetry is being used increasingly as a tool for hemodynamic
      monitoring via the Fick equation. This investigation was undertaken to examine
      the use of carbon dioxide elimination (VCO2A) and related respiratory quotient
      (RQA) to calculate oxygen uptake (VO2A) and estimate oxygen consumption (VO2)
      during steady-state and dynamic hemodynamic conditions. Nine patients undergoing
      abdominal aortic surgery were studied intraoperatively and Fick-derived
      hemodynamic measurements were made using a monitoring system employing indirect
      calorimetry, pulse oximetry, and pulmonary artery oximetry. Comparisons were made
      between measured VO2A and calculated VO2A derived from the VCO2A and the initial
      RQA (RQi), which is assumed not to change. Prior to aortic crossclamping (steady
      state), there were no significant differences between the measured and calculated
      methods with respect to oxygen consumption (184 +/- 24 ml/min vs 185 +/- 17
      ml/min), oxygen delivery (753 +/- 141 ml/min vs 769 +/- 178 ml/min), and cardiac
      output (4.7 +/- 0.6 L/min vs 4.7 +/- 0.7 L/min). However, immediately following
      aortic unclamping (dynamic state), the RQA changed precipitously from the
      baseline RQi. Consequently, significant differences between the measured and
      calculated methods were noted in oxygen uptake (213 +/- 41 ml/min vs 193 +/- 25
      ml/min, p < 0.001), oxygen delivery (780 +/- 297 ml/min vs 716 +/- 296 ml/min, p
      < 0.001), and cardiac output (5.8 +/- 2.2 L/min vs 5.3 +/- 1.8 L/min, p < 0.001).
      Additionally, following unclamping, the peak VO2A was 242 +/- 49 compared with a
      cVO2A of only 198 +/- 22 (p < 0.01). We conclude that the use of VCO2A to
      calculate VO2A may lead to erroneous measurements under dynamic conditions, such
      as unclamping of the abdominal aorta.

PMID- 1395756
TI  - A study of rib biopsy.
AB  - A retrospective study of one decade of rib biopsy in four hospitals in Nashville,
      Tenn, showed 61 biopsies were done in 60 patients. The typical patient was a male
      in his seventh decade. Preferred operative technique was open biopsy with general
      anesthesia. One half of the patients had metastatic malignancy; most of the known
      primary tumors were lung cancer. About one fifth of specimens were normal ribs.
      Biopsy was done in nine of these because of false-positive scintigraphy. Accurate
      preoperative chest wall localization is critical in order to minimize
      intraoperative decision-making problems. Yield of rib biopsy should be increased
      by more careful clinical observation, including critical evaluation of bone
      scans, avoiding overinterpretation of physical findings and observing for healing
      of possible rib fractures.

PMID- 1395758
TI  - Accuracy of respiratory inductive plethysmography during wakefulness and sleep in
      patients with obstructive sleep apnea.
AB  - To assess the accuracy of the respiratory inductive plethysmograph (RIP) during
      sleep in obese patients with obstructive sleep apnea (OSA), we monitored 13
      patients with OSA during wakefulness and nocturnal sleep with simultaneous
      measurements of tidal volume from RIP and integrated airflow. Patients wore a
      tightly fitting face mask with pneumotachograph during wakefulness and sleep.
      Calibrations were performed during wakefulness prior to sleep and compared with
      subsequent wakeful calibrations at the end of the study. Patients maintained the
      same posture during sleep (supine, 11; lateral, two) as during calibrations.
      There were no significant differences in calibrations before sleep and after
      awakening. The mean error in 13 patients undergoing RIP measurements of tidal
      volume during wakefulness was -0.7 +/- 3.4 percent while that during sleep was
      2.1 +/- 14.9 percent (p < 0.001). The standard deviation (SD) of the differences
      between individual breaths measured by RIP and integrated airflow was 9.8 +/- 5.5
      percent during wakefulness and 25.5 +/- 18.6 percent during sleep (p < 0.001).
      During both wakefulness and sleep, errors in RIP tidal volume were not
      significantly correlated with body mass index. In 12 patients with at least 10
      percent time in each of stages 1 and 2 sleep, SD was greater in stage 2 sleep
      compared with wakefulness and stage 1 (p < 0.001). In three patients who
      manifested all stages of sleep, SD was greater in REM sleep than in wakefulness
      and all stages of non-REM sleep (p < 0.001). In three patients who manifested all
      stages of sleep, SD was greater in REM sleep than in wakefulness and all stages
      of non REM sleep (p < 0.001). This was associated with paradoxic motion of the
      rib cage in two patients during REM. We conclude that, despite increased errors
      in individual breath measurements during sleep, more marked during stages 2 and
      REM sleep, RIP is clinically useful to measure ventilation quantitatively in
      obese patients with sleep apnea. The criterion of a decrease of 50 percent in
      tidal volume assessed by RIP is appropriate to define hypopneas in such patients.

PMID- 1395757
TI  - Circulating endothelin is not extracted by the pulmonary circulation in man.
AB  - To determine whether endothelin is extracted from plasma during passage through
      the pulmonary circulation, we measured its concentration at several points,
      including the pulmonary artery and the left superior pulmonary vein in seven
      patients undergoing cardiac surgery. Endothelin concentrations were very similar
      at all sites sampled. In patients undergoing coronary artery bypass grafting,
      there is no net pulmonary clearance of endothelin.

PMID- 1395759
TI  - Analysis of induced sputum for the diagnosis of recurrent Pneumocystis carinii
      pneumonia.
AB  - We studied the sensitivity of ISA for diagnosis of second-episode PCP in AIDS
      patients. We induced sputum in 218 patients who had known or suspected AIDS and
      who had a presentation suggestive of PCP. All patients with negative sputum smear
      for PCP underwent BAL. Twenty-five patients were identified who had second
      episode PCP at least 30 days after initial diagnosis. Chest roentgenographic
      infiltrate patterns for these 25 patients were blindly scored as normal, diffuse,
      upper lobe or focal non-upper lobe. The sensitivity of ISA was 72 percent for the
      first episode of PCP, 72 percent for the second episode of PCP, 72 percent for
      patients with second-episode PCP who had initial PCP detected by ISA and 71
      percent for patients with second-episode PCP whose first episode of PCP was
      missed by ISA. Of the ten patients who were treated with AP, only one had a false
      negative sputum analysis. A comparison of patients who had second-episode PCP
      diagnosed by ISA with those who had false-negative sputum analysis showed no
      difference in time to relapse, chest x-ray film pattern (all diffuse) or use of
      AP.

PMID- 1395760
TI  - The effects of flosequinan on hemodynamics and oxygen delivery in cor pulmonale.
AB  - The hemodynamic effects of a new orally active vasodilator, flosequinan, were
      compared with placebo (single blind) over 24 h in eight patients with pulmonary
      hypertension secondary to severe chronic obstructive pulmonary disease. Mean
      pulmonary artery pressure was reduced by 5.1 (3.4, 6.7) mm Hg (mean 95 percent
      CI) (p < 0.003) and pulmonary vascular resistance was reduced by 70 (23, 189)
      dynes.s.cm-5 (p < 0.013) by active drug compared with placebo. Cardiac output
      increased significantly with flosequinan by 0.47 (0.03, 0.91) L/min (p < 0.04)
      and systemic oxygen delivery increased by 90 (50, 120) ml/min/m2) (p < 0.05). A
      significant reduction in systemic vascular resistance was observed, 132 (35,230)
      dynes.s.cm-5 (p < 0.02) but no significant changes were seen in systemic arterial
      blood pressure or arterial blood gas tensions. Flosequinan favorably altered
      pulmonary hemodynamics relative to systemic and resulted in a significant
      improvement in oxygen delivery. The hemodynamic and blood gas effects of this
      compound suggest that it is a promising vasodilator for the treatment of
      pulmonary hypertension.

PMID- 1395761
TI  - A prospective study of pulmonary function and gas exchange following liver
      transplantation.
AB  - Pulmonary function and gas exchange were prospectively studied in 95 patients
      before and 9 to 15 months following liver transplantation. Pretransplant, the
      most common PF abnormality was impaired efficiency of gas exchange as measured by
      Dss. As a group, the mean Dss was 78.0 +/- 16.6 percent predicted and was found
      to be less than 80 percent predicted in 50 patients. As a group, patients with
      the most severe liver diseases clinically (Child's C classification) had the
      lowest mean Dss pretransplant. Posttransplant, three findings were of clinical
      importance: PaCO2 significantly improved posttransplantation, suggesting a
      resolution of pretransplant respiratory alkalosis. Expiratory airflow
      obstruction, measured by a change in the FEV1/FVC, was extremely uncommon
      posttransplant. Mean Dss improved significantly in patients with Child's C
      severity of liver disease. The most frequent deteriorations in Dss statistically
      were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis,
      significant pleural effusions and hepatic retransplantation.

PMID- 1395762
TI  - Small bronchogenic carcinomas presenting as solitary pulmonary nodules. Bioptic
      approach guided by CT-positive bronchus sign.
AB  - To evaluate the utility of the CT bronchus sign in making a choice between
      transbronchial biopsy (TBB) and transthoracic needle aspiration (TTNA) as the
      first diagnostic procedure in a patient with a solitary pulmonary nodule (SPN),
      we reviewed the results of TBB and TTNA in 26 patients who had a bronchogenic
      carcinoma less than 3 cm, studied with thin-section CT. The patients were divided
      into two groups. Group 1 included ten cases with a third- to fifth-order bronchus
      sign. Group 2 included two cases with a sixth-order bronchus sign and 14 cases
      with absence of a bronchus sign. TBB was performed in all the patients;
      conversely, TTNA was carried out in 22 patients. In group 1, TBB gave a
      diagnostic yield in eight (80 percent) of ten patients, while TTNA was positive
      in three (42 percent) of seven patients (p > 0.05). Conversely, in group 2,
      results of TBB were normal in all the patients, while TTNA gave a diagnosis in 10
      (66 percent) of 15 patients (p < 0.05). We think that TBB should be considered
      the method of choice in diagnosing SPNs associated with a third- to fifth-order
      bronchus sign; conversely, TTNA is more useful than TBB in diagnosing SPNs in the
      presence of a more peripheral bronchus sign or with the absence of a bronchus
      sign. In conclusion, we suggest routine evaluation with thin-section CT of each
      SPN to optimize diagnostic management.

PMID- 1395763
TI  - Bronchiolitis obliterans organizing pneumonia associated with systemic lupus
      erythematosus.
AB  - Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity
      characterized by the formation of plugs of fibrous tissue in bronchioles and
      alveolar ducts. It has been described in association with several connective
      tissue diseases including rheumatoid arthritis, polymyositis-dermatomyositis, and
      mixed connective tissue disease. Well-documented reports of BOOP in patients with
      systemic lupus erythematosus (SLE) are limited. We report two patients with SLE
      who presented with subacute respiratory illnesses due to BOOP, adding further
      strength to the association of this entity with SLE.

PMID- 1395764
TI  - Normobaric measurement of arterial oxygen tension in subjects exposed to
      hyperbaric oxygen.
AB  - This study demonstrates the ability of an automated blood gas analyzer
      (Radiometer ABL 330) operated at atmospheric pressure to measure the arterial
      oxygen tension (PaO2) of ten healthy volunteers exposed to hyperbaric oxygen
      (HBO2) up to 3.0 atmospheres absolute. Arterial blood samples were aspirated from
      subjects compressed in a single-person hyperbaric chamber and were analyzed
      immediately in the blood gas analyzer. The subjects' values for PaO2 correlated
      with the calculated alveolar O2 tension (PAO2) (measured PaO2 = 0.827 x PAO2
      15.1) (r2 = 0.97). Tonometric experiments indicated a difference between saline
      and blood PO2 measurements. We therefore derived a correction factor for blood
      measurements (corrected PaO2 = 0.908 x PAO2-52.4) (r2 = 0.98). These results
      compared favorably with PaO2 measurements made with blood gas analyzers
      calibrated inside walk-in hyperbaric chambers. We conclude that the PaO2 of
      normal subjects exposed to HBO2 can be measured accurately at atmospheric
      pressure with this automated blood gas analyzer. Prior to this study, hyperbaric
      PaO2 measurements could only be performed within walk-in chambers. Our
      observations generalize the normobaric measurement of hyperbaric PaO2 to patients
      treated in single-person and walk-in chambers.

PMID- 1395765
TI  - The conduction system in transplanted hearts.
AB  - This is a serial section examination of the conduction system (CS) in six
      patients who died seven months, 11 months, two years four months, four years two
      months, 11 years, and 16 years eight months following cardiac transplantation.
      The heart was hypertrophied and enlarged in all. There was myocarditis of varying
      degree in all cases with arteriosclerosis and arteriolosclerosis. These findings
      were more dominant in the atria than in the ventricles. In the CS, myocarditis
      with fibrosis was found in all in the approaches to the sinoatrial (SA) node, the
      SA node, the atria, the atrioventricular (AV) node, and the bundle and bundle
      branches, to a varying degree. When compared with the endomyocardial biopsy
      findings, the autopsied cases revealed more myocarditis and fibrosis than those
      estimated to be present in the biopsy specimen. In summary, this study
      demonstrates that there are fibrotic changes in the CS with the persistence of
      inflammatory phenomena of the myocardium and the CS to a varying degree in
      transplanted hearts. This is accompanied by the ubiquitous coronary artery
      disease affecting not only the large coronaries but also the small vessels. The
      pathologic changes in and around the CS may be responsible for arrhythmias and
      sudden death in some cases of cardiac transplantation.

PMID- 1395766
TI  - Oral vs intravenous dipyridamole echocardiography for detecting coronary artery
      disease.
AB  - The usefulness of the intravenous dipyridamole-echocardiography test (12-lead and
      two-dimensional [2-D] echo monitoring during dipyridamole infusion) in the
      diagnosis of coronary artery disease recently has been suggested. However, the
      intravenous form of dipyridamole is not available for clinical use in some
      countries and therefore the administration of oral dipyridamole has been employed
      in combination with echocardiography. In order to evaluate the relative
      usefulness of the oral (300 mg of pulverized tablets) vs the intravenous (up to
      0.84 mg/kg in 10 min) dipyridamole-echocardiography test, we performed the two
      tests, on different days and in random order, in 28 inhospital patients: 21 had
      coronary artery disease (seven had one-vessel disease, eight had two-vessel
      disease, and six had three-vessel disease); seven patients had no significant
      coronary artery disease. For both tests, the diagnostic end-point was the
      development of a transient dyssynergy of contraction. Sensitivity was 95 percent
      for the intravenous and 52 percent for the oral dipyridamole-echocardiography
      test (p < 0.01); in positive cases, the dyssynergy after the dipyridamole
      administration appeared at 6.5 +/- 2.5 min for the intravenous and at 27.8 +/-
      12.4 min for the oral test (p < 0.01). Specificity was 100 percent for both the
      intravenous and oral dipyridamole-echocardiography test. One or more extracardiac
      side effects (headache, gastrointestinal upset, flushing, etc) occurred in 61
      percent of the intravenous and 68 percent of the oral tests (p = ns). Nine
      patients with a positive intravenous and oral dipyridamole-echocardiography test
      also had a positive exercise-electrocardiography test. A significant correlation
      between exercise time (ie, the time from onset of exercise and 0.1 m V of ST
      segment shift) and dipyridamole time (ie, the time from onset of dipyridamole
      administration and the development of frank dyssynergy) was present for the
      intravenous (r = 0.6, p < 0.05) but not for the oral test. We conclude that the
      oral dipyridamole-echocardiography test, in comparison with the intravenous
      dipyridamole-echocardiography test, has a lower sensitivity and requires a
      substantially longer imaging time. The dipyridamole time is related to exercise
      time for intravenous but not for the oral dipyridamole-echocardiography test.

PMID- 1395767
TI  - Does radial artery pressure accurately reflect aortic pressure?
AB  - STUDY OBJECTIVE: Our objective was to determine whether the systolic, diastolic,
      and mean arterial pressures measured in the radial artery accurately reflect
      corresponding pressures in the ascending aorta in narcotic-anesthetized patients
      with known obstructive coronary artery disease, before being subjected to
      cardiopulmonary bypass (CPB). DESIGN: This was a prospective study. SETTING: The
      cardiac operating room of a large, tertiary-care university medical center.
      PARTICIPANTS: Fifty-one patients (45 men and six women; age range, 48 to 77
      years) with documented atherosclerotic coronary artery disease were studied. All
      patients underwent elective coronary artery bypass grafting after the study.
      INTERVENTIONS: Patients were premedicated with lorazepam and morphine 60 min
      before administration of Fentanyl-pancuronium anesthesia. The radial artery was
      cannulated before induction of anesthesia and the aorta approximately 45 min
      later. Comparisons of radial and aortic pressures were then performed.
      MEASUREMENTS AND RESULTS: Radial and aortic pressures were recorded through
      standard, fluid-filled, high-pressure, 91-cm (36-in) long tubing and disposable
      transducers, meticulously cleared of air bubbles. Additional measurements
      included cardiac output, central venous pressure, core temperature, blood gas
      levels, and hematocrit reading. Radial-aortic pressure differences were as
      follows: systolic arterial pressure (SAP), 12 +/- 1 mm Hg; mean arterial pressure
      (MAP), -0.8 +/- 0.3 mm Hg; and diastolic arterial pressure (DAP), -1.0 +/- 0.3 mm
      Hg. All were significant (p < 0.001), but the SAP difference was more than ten
      times that of either the MAP or the DAP values. The coefficients of determination
      (r2) indicated that the radial-aortic dependence was 0.44 for the SAP, 0.90 for
      the DAP, and 0.98 for the MAP relationship. Plotting the respective differences
      against the arithmetic mean of simultaneously measured pressures indicated that
      the radial SAP was 4 to 35 mm Hg higher than the aortic in 42 patients (82
      percent) and was 10 to 35 mm Hg higher in 26 patients (51 percent); radial-aortic
      MAP differences clustered within 3 mm Hg in 47 patients (92 percent); radial DAP
      was +/- 3 mm Hg different from the aortic in 46 patients (90 percent). The
      largest MAP difference was -6 mm Hg in one patient. The largest DAP difference
      was +/- 5 mm Hg in three patients. CONCLUSIONS: In this group of patients, who
      were studied before undergoing CPB, the radial SAP gave a poor estimate of that
      present in the ascending aorta, since in more than 50 percent of the cases, the
      radial SAP was 10 to 35 mm Hg higher than that in the aorta. The radial MAP and
      DAP are reliable, since in 90 percent and 92 percent of the patients,
      respectively, the pressure differences were within +/- 3 mm Hg of those in the
      aorta.

PMID- 1395768
TI  - Influence of left ventricular filling profile on the effect of atrioventricular
      synchronous pacing.
AB  - We correlated the percentage of atrial contribution to left ventricular filling
      (percent AC) assessed by Doppler echocardiography with the hemodynamic benefit
      from atrioventricular synchronous pacing assessed by direct hemodynamic
      measurements. Subjects comprised 40 patients who underwent electrophysiologic
      catheterization because of unexplained syncope or bradycardia (< 40 beats/min).
      Femoral arterial and pulmonary capillary wedge pressure were recorded by
      catheterization, and cardiac output was measured by thermodilution during
      temporary atrioventricular synchronous (DDD, 70 beats/min with 150 ms of
      atrioventricular delay) and ventricular (VVI, 70 beats/min) pacing. Mitral inflow
      velocity by pulsed-wave Doppler echocardiography was recorded during DDD pacing
      and percent AC was obtained by calculating the ratio of mitral inflow velocity
      area during atrial systole to total mitral inflow velocity area during early
      diastole and atrial systole. The mean arterial pressure and the cardiac output
      increased significantly (99 +/- 16 mm Hg vs 90 +/- 15 mm Hg, p < 0.001; 4.6 +/-
      1.0 L/min vs 3.9 +/- 0.9 L/min, p < 0.001), and the mean pulmonary capillary
      wedge pressure decreased (7 +/- 4 mm Hg vs 10 +/- 4 mm Hg, p < 0.001) during DDD
      compared with VVI pacing. A significant positive correlation was observed between
      the percent AC and the increase in cardiac output (r = 0.58, n = 40, p < 0.01) or
      the increase in mean arterial pressure (r = 0.62, n = 38, p < 0.01) during DDD
      pacing. The percent AC did not significantly correlate with the decrease in
      pulmonary capillary wedge pressure. In conclusion, patients with larger percent
      AC may receive major benefit from atrioventricular synchronous pacing.

PMID- 1395769
TI  - Acromegalic cardiomyopathy. Left ventricular filling and hypertrophy in active
      and surgically treated disease.
AB  - Myocardial hypertrophy and interstitial fibrosis are common in acromegalic hearts
      and may induce left ventricular (LV) dysfunction. The transmitral flow pattern
      was examined by pulsed-wave Doppler in 20 patients with active acromegaly and
      nine with acromegaly cured by pituitary microsurgery. Control groups consisted of
      25 normal subjects and 13 patients with systemic hypertension. We related Doppler
      indices of LV filling (E and A peak velocities and E/A ratio) to the duration of
      acromegalic disease, the GH plasma levels and LV mass. The LV mass/BSA was
      significantly greater in active acromegaly (187 +/- 53 g/sq m) and systemic
      hypertension groups (161 +/- 48 g/sq m) than in cured acromegaly (125 +/- 35 g/sq
      m) and the normal control group (109 +/- 36 g/sq m) (p < 0.01 for both). No
      differences were found in the E peak velocity, A peak velocity, and E/A ratio in
      the groups with active acromegaly (E/A: 0.9 +/- 0.2), cured acromegaly (E/A: 0.9
      +/- 0.3), and systemic hypertension (E/A: 0.8 +/- 0.5). An E/A ratio < 1 was
      found in 13 patients with active and four with cured acromegaly; (p = NS). In the
      active acromegaly group, the E/A ratio was related to either LV mass or the
      duration of disease (r:-0.45 and -0.47, respectively; p < 0.05). In the cured
      acromegaly group, the E/A ratio was related to the duration of disease before
      surgery (r:-0.70; p < 0.05) and not to LV mass (r:0.12). In conclusion, an
      impairment in LV filling may be present not only in the patients with active
      acromegaly but also in those successfully treated by surgery after a long
      duration of the disease, despite normal LV mass. These LV filling abnormalities
      may be in part determined by nonreversible myocardial changes, such as
      interstitial tissue fibrosis.

PMID- 1395770
TI  - Residual volume in a general population. Effects of body size, age, cigarette
      smoking, and respiratory symptoms.
AB  - Residual volume (RV) was obtained by subtracting vital capacity from total lung
      capacity determined by the single breath helium dilution (TLCsb) to measure CO
      diffusing capacity in 2,680 subjects (8 to 64 years old) of a general population
      sample. There were 712 normal subjects (243 male and 469 female subjects)
      selected to evaluate the pattern of RV by age and to derive reference values for
      internal comparisons. From 8 to 20 years old, RV showed an increase because of
      the cross-sectional body size effect; after 20 to 30 years, RV was still
      increasing, however, at a lower level. Age and height coefficients were
      significantly related to RV in younger and older ages, both in male and female
      subjects. The RV percent predicted and RV/TLC percent were higher in smokers when
      compared to nonsmokers and exsmokers (the difference was significant in male
      subjects). A dose-response effect was observed between RV percent predicted,
      RV/TLC percent, and pack-years. The RV percent predicted and RV/TLC percent were
      significantly higher in smokers and nonsmokers with FEV1 percent predicted below
      the normal limit (the difference was significant in male subjects). Moreover,
      higher values of RV percent predicted and RV/TLC percent were observed in
      subjects with wheezy symptoms in male smokers and nonsmokers. A negative
      significant correlation was observed between RV/TLC percent and the diffusing
      capacity adjusted for lung volume (DL/VA) in smokers, exsmokers and nonsmokers of
      both sexes, confirming the hypothesis that the decrease in DL/VA may be ascribed
      to the enlargement of terminal air spaces. In conclusion, determination of RV by
      the single breath helium dilution method is suitable in epidemiology, and it
      allows additional important information for understanding the physiopathologic
      mechanisms related to the pathogenesis of chronic obstructive lung disease.

PMID- 1395772
TI  - Intrinsic PEEP and unilateral lung hyperinflation. Pathophysiology and clinical
      significance.
AB  - Over a 14-month period, three patients developed unilateral lung hyperinflation
      during mechanical ventilation as a manifestation of intrinsic PEEP. These
      patients all had a history of CAO and an inflammatory or fibrotic disease process
      involving the contralateral lung. Physicians caring for patients with CAO need to
      be familiar with this presentation of intrinsic PEEP due to the associated
      barotrauma and cardiac dysfunction which can result from it.

PMID- 1395771
TI  - Validation of a technique to assess maximal inspiratory pressure in poorly
      cooperative patients.
AB  - The maximal pressure that can be generated during an inspiratory effort against
      an occluded airway serves as an index of respiratory muscle strength. We devised
      a method that permits accurate measurement of MIP, with near maximal values, and
      does not require patient cooperation. Twenty-two critically ill intubated
      patients performed MIP maneuvers before and after coaching. For the initial 11
      patients, MIP was measured after the airway was occluded in 20 s with a one-way
      valve that permitted only exhalation. In the latter 11 patients, DS
      (approximately 1/3 VT) was added in an effort to increase respiratory drive
      before the noncoached MIP maneuver. We found no significant difference between
      coached and noncoached MIP maneuvers when P0.1 during the first 100 ms of
      inspiratory efforts prior to the noncoached MIP maneuver was greater than 2 cm
      H2O. Thus, MIP can be reliably measured in critically ill patients with or
      without coaching.

PMID- 1395773
TI  - Volume-assured pressure support ventilation (VAPSV). A new approach for reducing
      muscle workload during acute respiratory failure.
AB  - This study reports the preliminary clinical evaluation of a new mode of
      ventilation--volume-assured pressure support ventilation (VAPSV)--which
      incorporates inspiratory pressure support (PSV) with conventional volume-assisted
      cycles (VAV). This combination optimizes the inspiratory flow during
      assisted/controlled cycles, reducing the patient's respiratory burden commonly
      observed during VAV. Different from conventional PSV, VAPSV assures precise
      control of tidal volume (VT) in unstable patients. Eight patients with acute
      respiratory failure (ARF) were submitted to assisted ventilation under VAV and
      VAPSV. Patient's ventilatory workload (evaluated through the pressure-time
      product, mechanical work per liter of ventilation, and work per minute) and
      patient's ventilatory drive (occlusion pressure--P0.1) were significantly reduced
      during VAPSV. This "relief" was more evident among the most distressed patients
      (p < 0.001), allowing a reduction of more than 60 percent in muscle load, without
      the need of increasing peak tracheal pressure. Mean inspiratory flow (VT/TI), VT,
      and effective dynamic compliance were significantly increased during VAPSV,
      whereas the effective inspiratory impedance decreased. These mechanical
      advantages of VAPSV allowed a reduction of intrinsic PEEP, whenever it was
      present. Blood gas values were similar in both periods. We concluded that VAPSV
      is a promising form of ventilatory support. At the same time that it was able to
      safely assure a minimum preset VT, VAPSV reduced patient workload and improved
      synchrony between the patient and the ventilator during ARF.

PMID- 1395774
TI  - Maneuver-free determination of compliance and resistance in ventilated ARDS
      patients.
AB  - At present, most methods of lung mechanics analysis do not take nonlinearities of
      compliance and resistance into account. Nevertheless, nonlinearity of compliance
      is an inherent property of the respiratory system in ARDS and nonlinearity of
      resistance is an inherent property of the endotracheal tube. Herein we describe a
      computer-assisted multipoint method (LOOP) for breath-by-breath calculation of
      total respiratory system compliance (Ctrs) and total respiratory system
      resistance (Rtrs). Unlike our previously published method, LOOP excludes
      nonlinearities of compliance and resistance by confining the data used from the
      P/V/V loop to sequences with constant flow in inspiration and with steadily
      decreasing flow in expiration. LOOP was applied to five patients ventilated after
      open heart surgery (HEART group) and 12 patients ventilated for ARDS (ARDS
      group). The compliance results from LOOP were compared with the semistatic
      reference values corrected for intrinsic PEEP (CsST,IP). In the ARDS patients the
      compliance values from LOOP (46 ml/mbar) corresponded well with the semistatic
      compliance (CsST,IP = 42 ml/mbar). Despite the fact that there is no reference
      method for resistance known to date, we also determined the semistatic resistance
      (RsST) at end-inspiratory pause. The resistance values determined with LOOP were
      8.5 mbar/L/s (RsST = 7.3 mbar/L/s) in the HEART group and 11.1 mbar/L/s (RsST =
      8.6 mbar/L/s) in the ARDS group. LOOP gives a good correspondence between the
      linear RC model and the measured data in ARDS patients. In conclusion, LOOP
      requires neither an end-inspiratory pause (EIP) nor additional determination of
      intrinsic PEEP and gives Ctrs, automatically corrected for IPEEP, as well as Rtrs
      breath by breath at the bedside.

PMID- 1395775
TI  - Modification of the spacer device. Use in the patient with arthritis or an
      artificial airway.
AB  - The spacer device minimizes oropharyngeal deposition of metered dose inhaler
      (MDI) medication and helps ensure consistent delivery of the medications to the
      bronchial tree. Patients with hand limitations and artificial airways may be
      unable to use an MDI. We describe several modifications to two currently
      available spacer devices for use in these populations.

PMID- 1395776
TI  - Role of platelet-activating factor in pulmonary edema after coronary ligation in
      dogs.
AB  - To evaluate whether PAF is related to the precipitation of pulmonary edema after
      myocardial ischemia, we studied the effect of a specific PAF antagonist, CV-6209,
      on the extravascular lung water level measured by the thermal-dye double
      indicator dilution method, ETV, after coronary ligation in dogs. Eight dogs
      served as sham control animals (group 1). The proximal left anterior descending
      coronary artery was ligated for 45 min in eight dogs (group 2), and the coronary
      artery was ligated after pretreatment with CV-6209 (1 mg/kg) in eight dogs (group
      3). The ETV increased significantly after coronary ligation in groups 2 and 3.
      The amount of increase in ETV in group 2 was significantly larger than in group
      3. Thus, CV-6209 can prevent the accumulation of extravascular lung water after
      coronary ligation without producing changes in pulmonary vascular dynamics,
      indicating that PAF may play an important role in pulmonary edema after
      myocardial ischemia.

PMID- 1395779
TI  - Solitary pulmonary nodule in a patient without asbestos exposure.

PMID- 1395778
TI  - Neuromuscular blockade in the intensive care unit.

PMID- 1395777
TI  - Evaluation of airway smooth muscle contractions in vitro by high-frequency
      ultrasonic imaging.
AB  - To visualize ASM contraction in vitro, we measured changes in cross-sectional
      area and inner circumference of isolated porcine and human bronchi in response to
      acetylcholine or carbamylcholine chloride (Carbachol) using high-frequency
      ultrasound. A mechanical ultrasonic catheter (20 MHz; diameter, 1.7 mm; echo
      element, 1 mm2) demonstrated three histologic layers (mucosa, cartilage and
      adventitia) and allowed measurement of dose-dependent contraction of porcine
      bronchi over time. Acetylcholine (10(-4)M) significantly decreased the cross
      sectional area by 17 +/- 2.85 percent but did not change the circumference. The
      mean initial value for area was 0.6 +/- 0.08 cm2 and for circumference was 3.0 +/
      0.24 cm (n = 5). The EC50 of acetylcholine was 1.5 x 10(-8) M. Carbachol (10(
      4)M)-induced contractions of human bronchi were also observed under the same
      conditions. In conclusion, high-frequency ultrasonic imaging can be used to study
      the morphology of ASM contractions in vitro, providing valuable information on
      the natural dynamics of ASM.

PMID- 1395781
TI  - Aortico-left atrial fistula in aortic valve endocarditis.
AB  - Aortic root abscess is a well-known complication of aortic valve endocarditis.
      This report describes the two-dimensional echocardiographic findings in a patient
      with aortic valve endocarditis whose course was complicated by a posterior aortic
      root abscess which ruptured into the left atrium creating an aortico-left atrial
      fistula, which, to our knowledge, has not been previously reported. These
      findings were confirmed at surgery.

PMID- 1395780
TI  - Mediastinal lymph node enlargement as a result of mitral valve stenosis.
AB  - Two patients are described with severe MVS, pulmonary venous hypertension and
      enlarged mediastinal, pulmonary and hilar lymph nodes. These enlargements were
      diagnosed on a preoperative chest CT. After MV replacement these enlarged lymph
      nodes nearly all resolved. The lymphadenopathy should be considered to be
      secondary to MVS with pulmonary venous hypertension.

PMID- 1395782
TI  - Bronchial dehiscence associated with a large broncholith in a lung transplant
      recipient.
AB  - A 63-year-old man who underwent single lung transplantation for advanced
      emphysema had a postoperative course complicated by asymptomatic bronchial
      dehiscence associated with a large broncholith. The stone eventually caused
      airway obstruction requiring partial fragmentation and incomplete extrication. We
      suggest that calcified nodes of significant size be removed at the time of
      surgery in the lung transplant recipient.

PMID- 1395783
TI  - Successful discontinuation of ventilation via tracheostomy by substitution of
      nasal positive pressure ventilation.

PMID- 1395784
TI  - Unilateral pulmonary edema. An unusual cause.
AB  - A patient presented with shortness of breath without fever, cough or sputum
      production. The patient was hypoxic without leukocytosis and a chest x-ray film
      demonstrated a right unilateral pulmonary infiltrate. A chest CT showed a large
      ascending thoracic aortic aneurysm with dissection. During surgical repair, the
      aneurysm was noted to be compressing the single right pulmonary vein. The
      infiltrate resolved postoperatively, and the patient has remained symptom-free
      for one year.

PMID- 1395785
TI  - Hamman's sign revisited. Pneumothorax or pneumomediastinum?
AB  - Louis Hamman described distinctive chest noises and emphasized their association
      with pneumomediastinum in 1937. However, the etiology of Hamman's sign remains
      incompletely defined and its association with pneumothorax underemphasized. We
      present a patient with pneumothorax and Hamman's sign assessed by computed chest
      tomography. Tomography suggested an alternate genesis of Hamman's sign; free
      pleural air may be cyclically channeled through a lung fissure thus creating
      chest sounds.

PMID- 1395786
TI  - External stabilization of flail chest using continuous negative extrathoracic
      pressure.
AB  - On rare occasions after total sternectomy, patients develop persistent flail
      chest deformities requiring long-term mechanical respiratory assistance. We
      report the use of a temporary external chest shell to deliver constant negative
      extrathoracic pressure (CNEP) to a long-term ventilated patient with flail chest.
      The patient's anterior thoracic cage stabilized, and significant improvement in
      pulmonary function was observed. With these data in hand, an operation was done
      to permanently stabilize the anterior chest wall by bone grafting.

PMID- 1395787
TI  - Unusual cause of hemoptysis. Hickman-induced cava-bronchial fistula.
AB  - A 56-year-old man with metastatic prostatic carcinoma underwent placement of a
      Hickman catheter. Approximately two months after the procedure, he was admitted
      to the hospital with hemoptysis and in respiratory distress. A contrast computed
      tomographic (CT) scan confirmed the diagnosis of a cava-bronchial fistula. The
      fistula was surgically repaired, and the patient made a satisfactory recovery.

PMID- 1395788
TI  - Ventilatory dysfunction in severe anorexia nervosa.
AB  - A 25-year-old woman suffering from chronic anorexia nervosa lost more than 50
      percent of her body weight and presented with generalized muscle weakness.
      Pulmonary function tests showed a severe restrictive defect, and she had marked
      impairment of respiratory muscle strength and endurance, peripheral muscle
      function, and hypercapnic ventilatory responses, all of which improved following
      refeeding. The interaction and response to treatment of these effects on
      respiratory function are discussed.

PMID- 1395789
TI  - Thoracoscopic resection of a posterior mediastinal neurogenic tumor.
AB  - Advances in endoscopic instrumentation and a growing enthusiasm for minimally
      invasive surgical techniques have sparked renewed interest in therapeutic
      thoracoscopy. We report the successful thoracoscopic resection of a posterior
      mediastinal nerve sheath tumor. A 35-year-old asymptomatic woman was found to
      have a posterior mediastinal mass on chest roentgenogram. Computed tomography and
      magnetic resonance imaging confirmed the presence of the lesion and showed no
      evidence of intraspinal extension. Exploratory thoracoscopy revealed a localized
      lesion without intraspinal extension. Thoracoscopic resection of the lesion was
      then performed. The patient's postoperative course was uncomplicated and she was
      discharged on the fifth postoperative day. The therapeutic potential of
      thoracoscopy continues to be realized as experience with the technique grows.

PMID- 1395790
TI  - Upper airway dysfunction in olivopontocerebellar atrophy.
AB  - We report the findings in a patient known to have olivopontocerebellar atrophy
      who developed respiratory distress, inspiratory stridor, and maximum inspiratory
      and expiratory flow volume loops. Treatment with carbidopa-levodopa gave
      symptomatic relief.

PMID- 1395792
TI  - Tricuspid valve regurgitation following blunt thoracic trauma.
AB  - Valvular lesions following blunt thoracic trauma are uncommon. Tricuspid valve
      regurgitation occurs very rarely. We report a successful tricuspid valve
      reconstruction for rupture of the chordae tendineae in a young man nine years
      after a motor vehicle accident. The value of echocardiography and transesophageal
      echocardiography for the diagnosis and quantification of this valve lesion is
      stressed.

PMID- 1395791
TI  - Thrombosed pulmonary artery aneurysm. A rare cause of a high-probability lung
      scan.
AB  - The high-probability ventilation-perfusion lung scan is accepted as supportive of
      pulmonary embolism and often negates further diagnostic evaluation; however,
      there are processes that mimic the clinical presentation and radiographic
      findings of pulmonary emboli, including a unilateral segmental or greater
      perfusion defect. We present the findings in a patient whose presentation and
      ventilation-perfusion scans over a three-month course were suggestive of
      pulmonary embolism, yet pulmonary angiography revealed a thrombosed pulmonary
      artery aneurysm. The interpretation of a unilateral segmental perfusion defect as
      high probability does not secure the diagnosis of pulmonary embolism and should
      not preclude further evaluation for alternative etiologies.

PMID- 1395794
TI  - Extreme hypercapnia in a fully alert patient.
AB  - A patient is described with decompensated chronic obstructive lung disease (COLD)
      and extreme hypercapnia. Despite an arterial CO2 level of 160 mm Hg, the patient
      remained awake and alert. This indicates that CO2 narcosis is not an invariable
      finding in severe hypercapnia.

PMID- 1395793
TI  - Interleukin-5 levels of pleural fluid and serum samples in a patient with PIE
      syndrome.
AB  - An increased production of IL-5 was detected in the pleural fluid (7.2 ng/ml) and
      in the serum samples (53 pg/ml) of a patient with PIE syndrome. Following steroid
      therapy, pleural fluid disappeared, eosinophilia improved and serum IL-5
      concentration became undetectable. These results suggested that eosinophilia in
      the PIE syndrome is a consequence of increased production of IL-5, especially in
      the lung.

PMID- 1395795
TI  - Periaortic hematoma formation leading to aortic valve failure. A complication of
      homograft placement for second valve surgery.
AB  - The aortic homograft has become the replacement valve of choice in the treatment
      of complicated endocarditis involving native and prosthetic aortic valves.
      Complications are rare, typically involving chronic leaflet degeneration causing
      valvular insufficiency or rarely chronic calcific stenosis. We present a case in
      which functional stenosis of the homograft valve was caused by compression and
      distortion by blood transmitted directly from the left ventricle into a space
      between the homograft and an external cavity formed by a Dacron wrap. The latter
      had been placed to help control suture-line bleeding. This case presentation
      demonstrates an unusual cause of homograft failure and suggests that wrapping of
      a homograft conduit by native aorta or an external Dacron wrap is not a
      substitute for meticulous surgical technique to assure a hemostatic suture line.

PMID- 1395796
TI  - Diffuse alveolar hemorrhage secondary to superwarfarin ingestion.
AB  - A 27-year-old woman with severe vitamin K deficiency presented with hemoptysis
      and diffuse pulmonary infiltrates. She rapidly developed respiratory failure
      requiring ventilatory support. Surreptitious ingestion of brodifacoum, a long
      acting warfarin derivative, was ultimately found to be the cause of her
      coagulopathy and DAH.

PMID- 1395797
TI  - Absence of lymphocytic alveolitis in patients with multiple sclerosis.

PMID- 1395798
TI  - Mycoplasma pneumoniae in the immunocompromised host.

PMID- 1395799
TI  - Iatrogenic complications of chest tube placement in demented patients.

PMID- 1395800
TI  - Nonsurgical management of bleeding secondary to tube thoracostomy. A case report.

PMID- 1395801
TI  - The unresponsive asthmatic. Misuse of a spacer system.

PMID- 1395802
TI  - Another complication of barotrauma.

PMID- 1395803
TI  - Tracheobronchomegaly.

PMID- 1395804
TI  - Cardiac dysfunction and pulmonary edema following scorpion envenomation.

PMID- 1395805
TI  - Routine monitoring of intracuff pressure.

PMID- 1395806
TI  - Possible role of tungsten oxide whiskers in hard-metal pneumoconiosis.

PMID- 1395807
TI  - Bronchoscopically induced bleeding.

PMID- 1395808
TI  - Effect of oxygen therapy on increasing PaO2 in hypoxemic patients with stable
      COPD while breathing ambient air.

PMID- 1395809
TI  - Effect of oxygen therapy on increasing PaO2 in hypoxemic patients with stable
      COPD while breathing ambient air.

PMID- 1395810
TI  - Pulmonary embolism associated with postoperative deep breathing.

PMID- 1395811
TI  - Measurement of cardiac output during exercise.

PMID- 1395812
TI  - Carbon dioxide narcosis. Pathological or "pathillogical"?

PMID- 1395813
TI  - Neuromuscular blockade. Should patients be relaxed in the ICU?

PMID- 1395815
TI  - Fiberoptic bronchoplasty. Description of a simple adjunct technique for the
      management of bronchial stenosis following lung transplantation.
AB  - Bronchostenosis is a well-recognized complication of pulmonary transplantation
      occurring at the site of the anastomosis and occasionally spreading distally from
      the original site of obstruction. The management of these airway complications
      has relied heavily on stent placement that usually involves the use of a rigid
      bronchoscope and is a relatively complicated procedure in the patient requiring
      mechanical ventilation. Another has been the use of laser therapy in selected
      patients. We report three cases of postoperative bronchostenosis managed with
      bronchoscopically directed balloon dilatation. This relatively simple procedure
      performed under local anesthesia using a fiberoptic bronchoscope and a
      modification of the Seldinger technique for balloon placement permitted accurate
      and atraumatic dilatation of significant posttransplant stenosis. This technique
      may have potential for emergency and/or palliative management of postoperative,
      posttraumatic, or malignant airway obstruction.

PMID- 1395814
TI  - Endobronchial tuberculosis. Clinical and bronchoscopic features in 121 cases.
AB  - The clinical and bronchoscopic features of endobronchial tuberculosis in 121
      patients were retrospectively investigated. The peak incidence occurred in the
      second decades, with 3.8 times higher incidence noted in female than in male
      subjects. A barking cough with sputum was the most common chief complaint in 61.1
      percent. Parenchymal infiltration and/or consolidation was the most common
      roentgenographic finding of the chest in 58.6 percent. Hypertrophy with luminal
      narrowing was the most common bronchoscopic finding in 43 percent.
      Bronchoscopically, right upper and right main bronchus were the most frequently
      involved in 30.5 percent. It was concluded from these data that using fiberoptic
      bronchoscopy allows not only substantial meaningful assessment of endobronchial
      tuberculosis but also relieves atelectasis eventually resulting in successful
      treatment with antituberculosis drugs.

PMID- 1395816
TI  - Bronchoalveolar lavage cell count and differential are not reliable indicators of
      amiodarone-induced pneumonitis.
AB  - Amiodarone-induced interstitial pneumonitis is a serious, frequently fatal
      untoward effect of a commonly used antiarrhythmic agent. Recent reports suggest
      that bronchoalveolar lavage (BAL) fluid cellular analysis might be used to
      diagnose amiodarone-induced pneumonitis. The purpose of this study was to
      determine if the diagnosis of amiodarone-induced pneumonitis could be made by
      patient history, pulmonary function evaluation, and examination of BAL fluid. We
      studied five groups of patients. Three of the five groups received amiodarone:
      patients receiving amiodarone without evident lung toxic reaction, patients with
      amiodarone-induced pneumonitis, and amiodarone-treated patients diagnosed as
      having other pathologic processes involving the lung. The two other groups
      examined were healthy volunteers and patients with interstitial lung disease from
      causes other than amiodarone. Pulmonary function tests included vital capacity
      (FVC), first second forced exhaled volume (FEV1), total lung capacity (TLC), and
      diffusing capacity for carbon monoxide (DCO). BAL fluid analysis included total
      and differential cell counts. We found that amiodarone-induced interstitial
      pneumonitis was not associated with an alteration in pulmonary function or BAL
      cellular composition which could permit its distinction from amiodarone-treated
      patients diagnosed as having an unrelated pulmonary process or patients with
      interstitial lung disease from other causes. The most frequent abnormality
      encountered in patients with amiodarone toxicity was a reduction in the
      percentage of macrophages in the differential cell count. The sensitivity,
      specificity, and predictive value of this finding was 82 percent, 69 percent, and
      69 percent, respectively. The sensitivity, specificity, and predictive value of a
      > or = 15 percent reduction in DCO was 44 percent, 50 percent, and 36 percent,
      respectively. We conclude that amiodarone-induced interstitial pneumonitis
      remains a diagnosis of exclusion, and the role of BAL fluid analysis is to narrow
      the differential diagnosis through microbiologic culture and cytologic
      examination.

PMID- 1395817
TI  - Antithrombotic therapy. Introduction.

PMID- 1395818
TI  - Rules of evidence and clinical recommendations on the use of antithrombotic
      agents.

PMID- 1395819
TI  - Aspirin and other platelet-active drugs. The relationship between dose,
      effectiveness, and side effects.

PMID- 1395820
TI  - Hemorrhagic complications of anticoagulant treatment.

PMID- 1395821
TI  - Hemorrhagic complications of thrombolytic therapy in the treatment of myocardial
      infarction and venous thromboembolism.

PMID- 1395822
TI  - Assessment of the therapeutic use of n-3 fatty acids in vascular disease and
      thrombosis.

PMID- 1395823
TI  - Use of antithrombotic agents during pregnancy.

PMID- 1395824
TI  - Prevention of venous thromboembolism.

PMID- 1395825
TI  - Antithrombotic therapy for venous thromboembolic disease.

PMID- 1395826
TI  - Antithrombotic therapy in atrial fibrillation.

PMID- 1395827
TI  - Antithrombotic therapy in valvular heart disease.

PMID- 1395828
TI  - Antithrombotic therapy in patients with mechanical and biological prosthetic
      heart valves.

PMID- 1395829
TI  - Antithrombotic agents in coronary artery disease.

PMID- 1395830
TI  - Coronary thrombolysis.

PMID- 1395831
TI  - Antithrombotic therapy in patients with saphenous vein and internal mammary
      artery bypass grafts following percutaneous transluminal coronary angioplasty.

PMID- 1395832
TI  - Antithrombotic therapy in peripheral arterial occlusive disease.

PMID- 1395833
TI  - Antithrombotic therapy for cerebrovascular disorders.

PMID- 1395834
TI  - Decision analytic and cost-effectiveness issues concerning anticoagulant
      prophylaxis in heart disease.

PMID- 1395835
TI  - Viral hepatitis control in China. A brief review on the present status of viral
      hepatitis in China.

PMID- 1395836
TI  - Study on the mechanisms of chronicity of hepatitis B infection.

PMID- 1395837
TI  - A six-year survey of immunogenicity and efficacy of hepatitis B vaccine in
      infants born to HBsAg carriers.
AB  - Although the efficacy of hepatitis B vaccine is well documented, the duration of
      immunity of healthy infants after vaccination is unknown. 99 infants born to
      hepatitis B surface antigen (HBsAg)-carrier mothers were studied and found to
      have positive anti-HBs (titer: greater than or equal to 10 mIU/mL) after a first
      injection of vaccine at the ages of 1 to 6 years. The infants were randomly
      divided into four groups of recipients treated with the vaccine of the National
      Institute of Allergy and Infectious Diseases (NIAID), U.S.A. or that of the
      Beijing Biological Products Research Institute (BBPRI), BBPRI vaccine in
      combination with hepatitis B immune globulin (HBIG) and placebo. The results
      showed that the protective efficacy dropped considerably after 5 years with NIAID
      vaccine, after 3 years with BBPRI vaccine and after 4 years with BBPRI vaccine
      plus HBIG. This suggests that a booster injection is needed 5 years after the
      first injection of NIAID vaccine, 3 years after BBPRI vaccine, and 4 years after
      BBPRI vaccine plus HBIG.

PMID- 1395838
TI  - Elimination of immune tolerance to hepatitis virus in an animal model.
AB  - Four-day old ducklings were infected with duck hepatitis B virus to simulate
      perinatal transmission of hepatitis B virus. Immune tolerance was characterized
      as persistent viremia, antigenemia, without detection of anti-DHBs or anti-DHBc.
      A synthetic peptide, P125-146, mimicking one of the epitopes of the native DHBV
      Pre-S protein was used to cross-link to tetanus toxoid or phytohemagglutinin.
      These 'novel' antigens were used to immunize immune tolerant ducks, aimed at
      bypassing T cell tolerance. After 5 injections, though no anti-DHBV Pre-S was
      detected, around 50% of the immunized ducks showed seroconversion to DHBV DNA
      negative.

PMID- 1395839
TI  - Hepatitis D virus infection in liver tissues of patients with hepatitis B in
      China.
AB  - 2,346 liver samples from 17 cities of China for intrahepatic hepatitis D antigen
      (HDAg) were studied by direct enzyme-labelled technique. HDAg was detected in 167
      out of 1,764 samples of HBsAg positive individuals making a detection rate of
      9.47%. Hepatitis D virus (HDV) infection existed in all the examined districts
      with no significant difference in the HDAg detection rate. It was found that the
      intrahepatic HDAg detection rate was related to the pathologic type of the liver
      disease. The HDAg detection rate in chronic liver diseases and severe hepatitis
      was higher than in other liver diseases. It suggests that HDV infection is
      associated with the progression and chronicity of the liver disease. Studies on
      the relationship between HDV infection and HBV replication showed that HBV
      replication might be suppressed by HDV infection. Both HDV and HBV, however,
      could replicate in the same hepatocyte simultaneously.

PMID- 1395840
TI  - Preliminary report on seroepidemiology of HCV and HBV infection in northern
      China.
AB  - 1 141 serum samples from various population groups in north China were examined
      for C100-3Ab by ELISA. Antibody to C100-3 antigen derived from HCV genome (C100
      3A) and HBsAg were measured in 438 normal population in Beijing. The C100-3Ab
      positive rate was 2.1% and the HBsAg positive rate was 2.5%. There is increased
      occurrence with age. In 649 cases of chronic liver diseases, the HBsAg positive
      rate was 87.1% in chronic persistent hepatitis (CPA), 88.8% in chronic active
      hepatitis (CAH), 64.9% in liver cirrhosis (LC) and 67.3% in hepatocellular
      carcinoma (HCC). The C100-3Ab positive rate was 10.5% (CPH), 12.1% (CAH), 42.6%
      (LC) and 38.4% (HCC). It is noteworthy that the C100-3Ab positive rate
      significantly increased with disease progression from CPH to CAH, LC and HCC.
      Prevalence of cases positive for both C100-3Ab and HBsAg was 0% in the normal
      population, 6.7% in CPH, 8.4% in CAH, 31.1% in LC and 28.8% in HCC. Investigation
      of patients with HCV infection showed that only 36.8% had blood transfusions. HCV
      and HBV infection may play important pathogenic roles in CPH, CAH, LC and HCC in
      north China.

PMID- 1395841
TI  - Ultrastructural study on extrahepatic infection of duck hepatitis B virus in
      ducks.
AB  - Kidney and pancreas tissues from congenitally infected Ma ducks with duck
      hepatitis B virus (DHBV) were examined by immunohistochemical staining technique
      and electron microscopy. The immunostaining showed that DHBV antigen was
      localized in the cytoplasm of tubular epithelial cells of kidney and acinar cells
      of pancreas of infected ducks. Under electron microscope, we found that complete
      and incomplete DHBV particles existed in the dilated cisternae of rough
      endoplasmic reticulum of both the cells. The size of complete and incomplete
      virus particles was nearly uniform in both the cells, 50-65 nm and 40-50 nm in
      diameter respectively. Therefore, extrahepatic infection and replication of DHBV
      were directly demonstrated ultrastructurally.

PMID- 1395842
TI  - A study of Chinese knee joint geometry for prosthesis design.
AB  - This study for the first time provides the geometric parameters of the knee joint
      of Chinese, which is indispensible to the design of knee prosthesis used for
      compatriotic patients. Thirty-five items, including linear, radial and angular
      measurements, were taken from 105 cadaveric knees and knee X-ray films of 1,100
      subjects. The method and calculation for proper correction of the X-ray image
      magnification and joint cartilage space was established. Correlation was found to
      exist between the X-ray correction coefficients and the body weight, which formed
      the basis for individualized correction of X-ray measurements. Statistical
      analysis revealed that most of the linear and radial measurements were highly
      related while the angular measurements were independent of others. Principal
      component analysis showed that the width of femoral condyle might be taken as the
      leading index in determining the dimension of the knee, and regression functions
      were established to supply the serial parameters for prosthetic design.
      Multivariate discriminate functions could aid the selection of knee prosthesis.

PMID- 1395843
TI  - A clinical study on diabetic retinopathy.
AB  - A clinical research on the diabetic retinopathy(DR) is reported. In the 662 cases
      of diabetes mellitus examined, the prevalence of DR was 51.3%, of which 7.6% were
      preproliferative and 7% proliferative. The study showed that when the disease
      progressed to the preproliferative and proliferative DR, laser photocoagulation
      could be the best treatment of choice, and panretinal photocoagulation was also
      quite effective in the treatment of pregnant patients with proliferative diabetic
      retinopathy.

PMID- 1395844
TI  - The arch structure of trabeculae in normal femoral head and its biomechanical
      significance.
AB  - The microstructure of the normal human femoral head was observed under light and
      electron microscope. Most of the trabeculae were seen in the form of arch
      structure, and the collagen fibers and mineral columns among the trabeculae were
      arranged in different directions. These findings provide a new explanation of the
      mechanism by which the femoral head can bear high stress without collapse.

PMID- 1395845
TI  - DNA content and its relationship with pathology and prognosis of colorectal
      carcinoma.
AB  - The DNA content of 181 colorectal cancers was investigated by flow cytometry on
      paraffin-embedded specimen. The relationship of flow cytometric DNA patterns of
      colorectal cancer to Dukes's stage, histological type and grade, tumor size and
      patient's prognosis were analysed. The DNA aneuploid carcinomas were found in
      53.04% of the patients (hypodiploid 22.10%, hyperdiploid 20.99%, polyploid
      9.94%). Diploidy was found in 46.96% of the patients with colorectal cancer. The
      proportions of aneuploidy were significantly lower in the patients with Dukes'
      stage A (25.00%) and B (47.14%) than those with Dukes' stage C (64.71%) and D
      (68.42%). Aneuploid frequency was higher in the patients with poorly
      differentiated adenocarcinoma (84.62%), mucinous adenocarcinoma (62.50%) and
      tubular adenocarcinoma (52.75%) than those with villous adenocarcinoma (22.86%).
      The proportion of aneuploidy was significantly higher in the patients with poorly
      differentiated tumor (71.79%) than in those with moderately (50.00%) and well
      differentiated tumors (44.83%). Five-year survival rate of the patients with DNA
      aneuploid tumors was 33.80% compared with 66.67% of those with diploid tumors.
      Analysis of Cox regression revealed that DNA ploidy and Dukes' stage
      significantly influenced the patient's prognosis. It is suggested that DNA ploidy
      might be an important prognostic factor in colorectal cancer.

PMID- 1395846
TI  - Transcoronary chemical ablation of ventricular tachycardia.
AB  - Transcoronary chemical ablation of ventricular tachycardia was recently performed
      in one patient with refractory ventricular tachycardia in our hospital. The
      procedure was successful. The arrhythmia was cured and no recurrence occurred in
      a 24-month period. The clinical application and mechanism of transcoronary
      chemical ablation were discussed.

PMID- 1395847
TI  - Pelvic lymphadenectomy with stripping technique in 43 cases.
AB  - Pelvic lymphadenectomy with stripping technique--Gao's stripping pelvic
      lymphadenectomy (GSPL) was introduced. From January to December 1989, this
      operation was performed on 43 patients (36 patients with cervical carcinoma, 5
      endometrial carcinoma and 2 ovarian carcinoma). The mean time of the operation
      was 12.56 minutes for the left side, and 13.33 minutes for the right side. No
      severe complications were found. The bleeding during operation was minimal. The
      main advantages of GSPL include high-speed operation, clean and integral
      lymphnodes stripped, less bleeding and complications, and easy performance of
      operation.

PMID- 1395848
TI  - Full-valve annuloplasty in treatment of primary deep venous valvular incompetence
      of the lower extremities.
AB  - Full-valve annuloplasty of superficial femoral venous valves was performed
      successfully in 139 extremities affected with primary deep venous incompetence of
      the lower limb. Chronic ulcerations in 43 affected extremities healed after
      operation. Postoperative venography showed that the recovery rate of valvular
      function was 97%, and no serious complication was noted. Follow-up for a mean of
      3.5 years showed no varicosed vein and no recurrence of ulceration. The
      principles of operation, the optimum site, number and degree of annuloplasty,
      indications and results of the operation were discussed.

PMID- 1395849
TI  - Mycosis fungoides with oral involvement.

PMID- 1395850
TI  - [Genetic techniques and medicine].

PMID- 1395851
TI  - [Quality assurance in medicine--from the viewpoint of the cost carrier].

PMID- 1395852
TI  - [Basic limits of quality assurance in medicine].

PMID- 1395853
TI  - [Quality assurance in medicine--from the viewpoint of the hospital insurance
      carrier].

PMID- 1395855
TI  - [Sonography in the postoperative course (abdomen and thorax)].

PMID- 1395854
TI  - [Sonography in acute abdominal emergency].

PMID- 1395856
TI  - [Sonography of soft tissues and joints].

PMID- 1395858
TI  - [Endosonography of esophageal cancer. Results of a clinical study and in vitro
      analysis].
AB  - From April 1989 to June 1991 63 patients with esophageal cancer were investigated
      by endosonography with the object of ascertaining the depth of intrathoracic
      tumor infiltration and lymphnode involvement. The sensitivity in diagnosing tumor
      infiltration amount to 0.74; the sensitivity for involvement of regional
      lymphnode was 0.84, specificity 0.44. In an in-vitro analysis endosonographic
      criteria for the assessment of regional lymphnodes are proved. Echogenic
      structure seems not to be a valuable criterium.

PMID- 1395857
TI  - [Functional sonography of blood vessels].

PMID- 1395859
TI  - [Importance of sonography in diagnosis of ileus. A retrospective study of 459
      patients].
AB  - In a retrospective trial we investigated the significance of ultrasound in the
      diagnosis of intestinal obstruction in 459 patients. The overall sensitivity was
      93.7%. In paralysis the correct diagnosis was obtained in 98% of all. Mechanical
      obstruction was identified in 91%. In cases of incomplete mechanical obstruction
      sensitivity was 89%. The corresponding value for complete obstruction was 95%. In
      all patients with negative findings on abdominal x-ray (10%) the correct
      diagnosis was established by ultrasound. Only in 71% of cases ultrasound was
      successful differentiating small bowel from large bowel obstruction. The
      underlying cause of ileus was yielded by ultrasound in 45% of the cases. On the
      basis of our experience ultrasound is proven to be of significant importance in
      the diagnosis and differentiation of ileus.

PMID- 1395860
TI  - [Surgery of blunt heart trauma].
AB  - Between 1972 and 1990 11 patients--all but one of them with multiple injuries-
      were treated surgically for blunt cardiac trauma caused by traffic accident in
      about 90%. Myocardial rupture (n = 3), laceration of the pericardial sac (n = 1),
      mitral insufficiency (n = 5; one of them in combination with atrial septal
      defect), ventricular septal defect (n = 1) and myocardial aneurysm (n = 1)
      occurred. Patients with myocardial rupture and pericardial laceration died within
      2 h after admission to hospital; the other patients were successfully treated by
      mitral valve replacement (n = 4), mitral valvuloplasty and repair of ASD, suture
      repair of VSD and resection of myocardial aneurysm in one case, respectively. The
      interval to operation was 8 months to 12 years. Whereas pericardial tamponade
      caused by rupture of the atrial or ventricular wall and injuries of main coronary
      vessels require immediate surgical intervention, valve insufficiencies, septal
      defects or myocardial aneurysms may be mostly treated at a later date.
      Improvement of logistic measurements and the suspicion of blunt cardiac trauma
      followed by immediate surgical intervention may reduce the mortality rate in
      cases of cardiac rupture.

PMID- 1395861
TI  - [New histomorphologic prognostic parameters in stomach cancer. A uni- and
      multivariate analysis of 445 patients].
AB  - In a retrospective series of 445 gastric cancer patients, the prognostic
      significance of classical histological parameters such as T-category, tumor size,
      lymphnode involvement and tumor grading was compared with the prognostic value of
      vascular invasion and the degree of tumor cell dissociation (TCD) at the invasion
      front. As shown in a Cox regression analysis, T-category had the highest
      prognostic value. Nevertheless, vascular invasion and TCD proved to be
      independent new parameters in a multivariate analysis, exceeding the prognostic
      information obtained by the combination of T-category and lymph-node involvement.
      In contrast, tumor grading provided no significant information. The determination
      of TCD at the invasion front as well as a careful search for vascular invasion
      may therefore provide additional useful information for identifying those
      patients who are at high risk and who may be candidates for adjuvant therapy in
      future clinical trials.

PMID- 1395862
TI  - [Prognostic factors in stomach cancer. Results of a uni- and multivariate
      analysis].

PMID- 1395863
TI  - [Technique of dynamic support suture and palisade closure].
AB  - In 35 cases a dynamic supporting suture was applied. The technique of a palisade
      closure and of a dynamic supporting suture is introduced as shown in three cases
      of complicated abdominal wall conditions. This allows a differentiated operative
      tactical procedure in the treatment of complicated laparotomy wounds following
      peritonitis, re-operation and wound dehiscence.

PMID- 1395864
TI  - [Fascia dehiscence--cause and prognosis].
AB  - During a period of 5 years, 4476 interventions in abdominal surgery were
      prospectively analyzed. The incidence of fascial dehiscence was 0.7% (n = 30).
      Seventeen of these patients underwent surgery on account of intraabdominal
      infection (total incidence of intraabdominal infection 4.4%). Fascial dehiscence
      developed in 22 out of 30 patients (73%) after emergency surgery. All of them had
      to be operated out of routine surgical schedule with the exception of four
      patients. Using multivariate stepwise logistic regression analysis, main
      determinant factors in fascial dehiscence were the ASA score (p = 0.0001),
      reflecting the severity of primary or concomitant diseases, and wound infection
      (p = 0.0075), mostly due to intraabdominal contaminations. Fascial dehiscence was
      associated significantly with a higher morbidity, reflected by longer inpatient
      management. Nevertheless, the overall lethality of 20% was associated to serious
      primary or concomitant diseases. Therefore, the results emphasize the
      significance of diligent preoperative work-up. Adequate treatment for concomitant
      disorders should be performed preoperatively, whenever possible even in emergency
      surgery.

PMID- 1395865
TI  - [Traumatic aneurysm of the celiac trunk].

PMID- 1395866
TI  - [Spontaneous dissection of the common carotid artery].

PMID- 1395867
TI  - [Pseudoaneurysm with pseudocystocolic fistula in pancreatitis. A rare cause of
      lower gastrointestinal hemorrhage].

PMID- 1395868
TI  - [Open letter to the Federal Health Officer, Bonn, 27 July 1992. 1993 health
      policy law].

PMID- 1395869
TI  - [Open letter to the Federal Health office, Cologne, 3 August 1992. 1993 health
      legislation].

PMID- 1395870
TI  - [Legal liability and responsibility of the physician].

PMID- 1395871
TI  - [Legal expert assessment of perforated appendicitis].

PMID- 1395873
TI  - [Squamous cell cancer of the esophagus. Treatment concept at the National Cancer
      Center in Tokyo].

PMID- 1395872
TI  - [Squamous cell cancer of the esophagus. Treatment concept at the Houston M.D.
      Anderson Cancer Center].

PMID- 1395874
TI  - [Squamous cell cancer of the esophagus. Treatment concept at the Cologne
      University surgical clinic].

PMID- 1395875
TI  - [Randomized study of preoperative chemotherapy in squamous cell cancer of the
      esophagus. CAO Esophageal Cancer Study Group].
AB  - Only 46 of 77 patients with potentially resectable squamous cell carcinoma of the
      esophagus who were asked to participate in a phase-III trial to be treated by
      either immediate surgery (n = 24) or surgery plus preoperative chemotherapy (n =
      22) agreed to randomization. A priori 13 patients chose chemotherapy before
      surgery and 18 patients only surgery. The complete chemotherapy program consisted
      of three cycles with 5-FU (1g/m2/d x 5) and cisplatin (20 mg/m2/d x 5). The
      response rate (CR and PR) to chemotherapy was 47%. Side effects of therapy were
      higher than expected, based on results of previous phase-II studies. Two drug
      related deaths were observed. The resectability rate for patients in the
      operation-only group was 80 and 70% for patients receiving chemotherapy. The
      postoperative rate of septic complications (41 vs. 26%) and respiratory disorders
      (37 vs. 26%) were higher for patients with preoperative chemotherapy in
      comparison to the only surgically treated controls. Surgery related mortality was
      increased in the chemotherapy group (18%) compared to the controls (10%).
      Patients responding to preoperative chemotherapy had a prolonged survival (median
      13 months) when compared with non-responders (median 5 months), but the median
      survival for the chemotherapy group and the only-surgery group was identical (10
      months). We conclude, that the preoperative chemotherapy regime used in this
      multi-institutional trial neither influences resectability, nor increases overall
      survival of patients with localized esophageal cancer. However, preoperative
      chemotherapy was associated with considerable side effects and a high
      postoperative mortality.

PMID- 1395876
TI  - [Liver transplantation after trans-jugular intrahepatic portosystemic stent
      shunt].
AB  - Every third patient with parenchymal liver disease bleeds from esophageal
      varices. Treatment of this complication is of special interest with regard to
      liver transplantation which may become necessary later on. The mesocaval H-shunt
      excluded, surgical shunting results in technical and hemodynamic problems during
      transplantation. They may be avoided by the new approach of transjugular
      intrahepatic portosystemic stent shunt (TIPSS). We report our experience with
      liver transplantation in two patients after TIPSS.

PMID- 1395877
TI  - [Cardiac morbidity and fatalities in patients with vascular surgery.
      Identification of risk groups].
AB  - Incidence and type of cardiac complications in 701 patients undergoing arterial
      vascular surgery were prospectively investigated to identify high-risk groups.
      Cardiac morbidity was 10.1%. Cardiac complications were responsible for 28 deaths
      (57%). Using logistic regression analysis, age (cardiac morbidity greater than
      7017.3%), impaired renal function (19.8%), and congestive heart failure (17.3%)
      were the main independent risk factors. In addition, 4 risk factors (arrhythmia,
      coronary artery disease, anemia, emergency surgery) showed significant individual
      association with cardiac complications. Cardiac morbidity increased to 27.8% in
      patients with more than 2 of these 7 risk factors. A further association could be
      demonstrated between the degree of peripheral vascular disease and cardiac
      morbidity, but not with the extent of the operation. Based on our results a
      distinction between three groups of different cardiac risk can be made. A
      clinical algorithm for further cardiac assessment in high-risk patients is
      presented.

PMID- 1395878
TI  - [Functional results of subtotal and partial colectomy in therapy-resistant
      chronic constipation. A follow-up study of 32 patients].
AB  - In 32 female patients with severe constipation subtotal (n = 27) or partial (n =
      5) colectomy was performed. In 8 cases slow transit constipation was preexistent,
      24 patients had a megacolon/dolichocolon. Ileosigmoid anastomosis was found to
      show the most favourable results. None of these patients complained of
      constipation postoperatively and all of them reported regular (daily) bowel
      movements. Incontinence for flatus and/or liquid stools was less likely to occur
      with ileosigmoid than with rectal anastomosis (29 versus 46%).

PMID- 1395879
TI  - [Treatment of pilonidal sinus with excision and primary suture using a local,
      resorbable antibiotic carrier. Results of a prospective randomized study].
AB  - The excision of a pilonidal sinus with wound healing by second intention, often
      results in a long duration of treatment. On the other hand, primary suture after
      excision has a high rate of abscess formation. In a randomized study we treated
      40 patients with excision of pilonidal sinus, insertion of a collagen sponge
      containing Gentamicin and primary suture (group 1) to prevent this abscess
      formation. Another 40 patients were treated in the same way but without applying
      the Gentamicin-collagen sponge (group 2). There had been no significant
      differences as to the history and duration of the disease, the wound size, the
      degree of inflammation, the weight of the patients or the amount of hair near the
      sinus. In group 1 only 7.5% of the patients had a postoperative abscess
      formation, in contrast to group 2, with an abscess rate of 52.5% and consecutive
      surgery (p less than 0.001). One year after the operation the recurrence rate was
      0 in both groups. Considering the results mentioned, surgical excision of the
      pilonidal sinus in combination with insertion of a resorbable antibiotic sponge
      we recommend this therapy.

PMID- 1395880
TI  - [Thoracoscopic use of staplers. New possibilities for minimally invasive
      diagnosis and therapy].
AB  - Thoracoscopic resection of peripheral lung tissue is possible by using special
      staplers (Endo-GIA). Main indications for using this technique are the treatment
      of a spontaneous pneumothorax by resection of bullous lung areas (15 patients)
      and the excision of macro biopsies for diagnostic reasons (13 patients). It is
      reported about the technique and the early outcome of these 28 thoracoscopically
      performed lung resections. This way minimally invasive procedure is combined with
      well-established surgical technique.

PMID- 1395881
TI  - [Ultrasound assisted brachial plexus anesthesia].
AB  - Plexus brachialis anaesthesia is a common technique for hand and forearm surgery.
      If the distance between puncture site and plexus brachialis is to long the
      anaesthesia will be incomplete. If there happens a direct puncture and injection
      of anaesthetics in the nerves, neurological deficit can occur. Intravascular
      injection causes cardial complications. This problems can occur mainly in obese
      patients in whom the brachial artery cannot be identified well by clinical
      examination. In these patients we perform the plexus brachialis anaesthesia under
      sonographical control. For the examination we use a linear 7.5-MHz transducer.
      The technique is presented.

PMID- 1395882
TI  - [Subcutaneous gas emphysema as an intraoperative complication in laparoscopic
      laser cholecystectomy].

PMID- 1395883
TI  - [A severe intraoperative complication of cholecystectomy--massive hemorrhage and
      hemobilia].

PMID- 1395884
TI  - [Complex iatrogenic vascular injury in reoperation of inguinal hernia].

PMID- 1395885
TI  - [Intraoperative assessment and procedure in locally advanced rectal cancer].

PMID- 1395886
TI  - [Pain therapy with Toratex. Official satellite symposium of the Xth World
      Congress of Anesthesiology. The Haague, 15 June 1992].

PMID- 1395887
TI  - [Evaluation of antenatal monitoring of unconjugated estriol in the saliva].
AB  - A new radioimmunoassay kit for unconjugated salivary estriol (SE 3) determination
      was used to monitor 497 fetuses in late pregnancy, 217 normal and 280 at high
      risk. The SE 3 values of normal pregnancy were also measured in 1378 cases at
      20th to 41st gestational week. The normal concentration weekly was established.
      The results were 1. The false negative and false positive rate of SE3 were 2.0%
      and 0.6%, respectively; thus the correct rate of SE3 in prenatal prediction of
      fetal well-being was 97.4%, similar to that of serum E3 (95.6%, P greater than
      0.05) and significantly higher than that of overnight 12-hour urine E3/C (84%, P
      less than 0.05). 2. There were 8 fetal deaths of 11 cases with lower SE3,
      whereas, only one death due to nuchal cord in the 486 with normal SE3, and no
      perinatal death. It is highly important to collect saliva and measure the SE3
      correctly in order to guarantee accuracy of the results. The advantages of
      salivary SE3 assaying are reliable and being more scientific and practical than
      that of serum E3. We suggest that determination of SE3 may replace serum E3
      measurement for assessing fetal-placental well-being.

PMID- 1395888
TI  - [Prevention of post-operative infection by using antibiotics of 217 cases of
      cesarean section].
AB  - A prospective study was undertaken to compare the efficacy of local antibiotics
      irrigation with that of systemic antibiotics in Cesarean section patients in the
      prophylaxis of post-operative infection. 217 patients delivered by Cesarean
      section were randomly divided into three groups: (1) intrauterine and pelvic
      irrigation with ampicillin; (2) systemic use of penicillin+gentamycin
      (intravenously and intramuscularly); (3) control group: no antibiotics given. The
      incidences of post-operative infection for the two treatment groups were
      significantly lower than control group, and the difference of post-operative
      infection between the two treatment groups was not statistically significant. It
      suggests that administration of antibiotics either by local irrigation with
      ampicillin or by systemic using of penicillin+gentamycin are just as effective in
      preventing post-operative infection. In our study, 8 out of 10 of the positive
      cultures from the uterine cavity of non-elective Cesarean section cases became
      negative after irrigation. This implies that antibiotic irrigation has the effect
      of reducing bacterial flora locally. Two to three days after operation, the
      incidences of positive uterine cavity culture for the two treatment groups were
      lower than control group, but not of statistical significance. Therefore, it
      remains to be clarified whether prophylactic use of antibiotics can prevent the
      vaginal flora from ascending into the upper genital tract.

PMID- 1395889
TI  - [Prospective study of intrauterine fetal resuscitation with aminophylline].
AB  - 80 cases of fetal distress were divided at random into group A and B. Group A was
      treated with the traditional three drugs combination treatment. Group B was
      treated with intravenous injection of aminophylline slowly. FHR CTG and BPS were
      monitored and analysed. The results were as follows: (1) The differences before
      and after treatment in group B were significant. (2) Only FHR in group A showed
      difference before and after treatment. (3) The changes after treatment between
      group A and B were significant. These suggested that the effect of aminophylline
      on intrauterine fetal resuscitation is better method.

PMID- 1395890
TI  - [Prevention and factors inducing respiratory distress syndrome in prematures].
AB  - An analysis of 105 cases of prematures with respiratory distress syndrome, the
      idiopathic type were 9.5% (10/105). Fetal anoxia and ischemia, induced by
      pregnancy and during labour amounting to 87.6% (92/105), and of which 2.9%
      (3/105) was due to diabetes. It indicated that most cases of RDS are
      predominantly related with fetal anoxia and ischemia which results in pulmonary
      surfactant abnormality or impaired activity. It is important that in clinical
      diagnosis one should monitor cautiously the presence of premature birth with
      anoxia and ischemia, Thus, a preventive treatment must be given at least 24 hours
      prior to birth, and the earlier the least morbidity of RDS occurred.

PMID- 1395891
TI  - [Lung function changes during pregnancy].
AB  - The lung functions in different pregnant stages were measured in 41 women with
      pregnancy and 12 normal women without pregnant. Forced Vital Capacity (FVC) was
      found gradually decreasing as pregnancy advanced (P less than 0.05). After 28
      weeks of gestation, the Vital Capacity (VC), Forced Expired Volume in 1 second
      (FEV 1) significantly decreased as compared with the normal values (P less than
      0.01 or P less than 0.05). These results suggested that the lung function changed
      gradually during pregnancy, especially after the 28th week, significantly in VC,
      FVC and FEV 1. Maybe there are slight obstructions in the bronchial tubes. After
      the 28th week of gestation and it may be the reason for occurrence of breathshort
      and the lung infection.

PMID- 1395892
TI  - [Luteinization of unruptured follicles during clomiphene treatment].
AB  - Twenty-eight anovulatory, infertile patients under clomiphene (cc) treatment were
      studied. Ovarian function was ascertained through BBT, cervical score (cs) and
      serial hormonal assays. Follicular development and ovulatory events were
      monitored by serial ultrasonography. Of a total of 66 treatment cycles, 49
      presented ovulatory responses, but only 28 cycles showed actual ovulation (42.4%
      of total; 57.1% of ovulatory response cycles); follicles in 21 cycles were
      unruptured but luteinized (LUF) (31.8% of total; 42.9% of ovulatory response
      cycles); deficient follicular development occurred in 17 cycles. With analysis of
      parameters investigated and hormonal assays, the characteristics of LUF and some
      factors involved in its development are discussed.

PMID- 1395893
TI  - [Clinic-pathological study of 485 cases of postmenopausal bleeding].
AB  - Four hundred and eighty-five patients with postmenopausal bleeding (PMB) who
      underwent a curettage were studied retrospectively to evaluate the relationship
      of clinical cause and pathological findings. The results showed that nonorganic
      causes were the most common, benign causes were much commoner than malignant
      causes. Bleeding from the uterus was the most common in all PMB. Pathological
      examination revealed atrophic endometrium in 41.5%, proliferative and secretory
      endometrium only a few. Endometrial and cervical carcinoma were the most common
      among the malignant causes. PMB with an enlarged uterus, and women with advanced
      age have a statistically significant correlation with more serious pathology. It
      is suggested that the postmenopausal endometrium changes are regulated by ovarian
      and ectopic sex hormones, and endometritis or vascular diseases of the
      endometrium may be involved in the mechanism of bleeding.

PMID- 1395894
TI  - [Relation between macrophages in peritoneal fluid of endometriosis and
      infertility].
AB  - Peritoneal fluid was collected from 18 endometriosis-associated infertile
      patients and 14 unexplained infertile women. The cells were counted in a
      hemacytometer and subjected to morphologic analysis. The phagocytic activity on
      Candida Albicans and on Sperms was evaluated and the activity of acid phosphatase
      in the pelvic fluid and within the macrophages were measured. The results showed
      that the endometriosis samples have macrophages of large size as compared with
      the macrophages found in unexplained infertile or fertile women, the
      concentration of pelvic macrophages in endometriosis is higher, the phagocytic
      and bactericidal activity is also higher and the macrophages in endometriosis
      engulf sperms as well. The accentuated activity of pelvic macrophages may be
      associated with the infertility in patients with endometriosis.

PMID- 1395895
TI  - [Enhancing the treatment of pregnant complications].

PMID- 1395896
TI  - [Effect of placenta previa on fetal growth and development].
AB  - A retrospective study of 151 fetuses born of mothers with placenta previa in the
      maternity and our hospital in 1984-1991 was done. This study aimed at determining
      whether placenta previa affects growth and to what extend. We recorded the birth
      weight, crown-heel length, head and chest circumferences of each of the 151
      fetuses. After calculating the average of each item. According to gestational
      week and type of placenta previa, they were compared with the 50th percentile
      numbers in normal fetuses of the same gestational age. The results were among the
      151 features, born of mothers with placenta previa 19 (12.6%) suffered from
      intrauterine growth retardation, 80(53.0%) with birth weight less than normal
      fetuses, and 52(34.4%) with birth weight basically the same as normal fetuses.
      Most of the fetuses with birth weight less than normal, were born of mothers with
      total or partial placenta previa while most of those with birth weight basically
      the same as normal fetuses. At 28th to 32nd week were born mothers with lowly
      placenta previa of gestation there was no obvious difference between the birth
      weights of fetuses of placenta previa mothers and normal pregnancies (P greater
      than 0.05). But from 33rd week to 40th week, the difference became obvious (P
      less than 0.05); the chest circumference in fetuses of total and partial placenta
      previa cases obviously less (P less than 0.05). So we may say that placenta
      previa affects fetal weight gain, especially from 33rd week and the chest
      circumference, in the last three weeks.

PMID- 1395897
TI  - [Analysis of 65 cases of abruptio placenta].
AB  - From Jan 1, 1971 to Dec 12, 1990, 65 cases of abruptio placenta were admitted to
      our hospital. The incidence was 0.19%. Among them, thirty were complicated by
      pregnancy induced hypertension (46.2%). The perinatal fetal mortality was 19.7%;
      perinatal death occurred mostly in the premature group. All babies survived
      except two abnormalities. Cesarean section rate was 32.3%. All postpartum
      hemorrhage 29.2%. Couvelaire uterus 6.2%, were cured by conservative treatment.
      There was neither stillbirth nor newborn death in the thirty three cases treated
      expectant, but a newborn asphyxia rate of 6.1% and a cesarean section rate of
      15.1%. Analysis showed that abruptio placentae should be suspected in cases with
      abnormal fetal heart rate of unknown cause accompanying signs of labor, premature
      labor of unknown cause, uterine tongue, ultrasonically visualized liquid from
      dark area behind the placenta, besides classical signs of abdominal pain and
      vaginal bleeding. Expectant treatment is appropriate if gestational age is small
      and no acute symptoms exists so as to minimize the perinatal mortality and
      cesarean section rate.

PMID- 1395898
TI  - [Diagnosis and management of obstetric acute disseminated intravascular
      coagulation].
AB  - Twenty-seven in-patients with obstetric DIC in our hospital from Jan. 1971 to
      Dec. 1990 were analysed retrospectively. The incidence was 0.12% in the first
      decade and 0.02%, in the second, showing a difference of significance between
      them. The most common predisposing factors included amniotic fluid embolism,
      abruptio placenta and hemorrhagic shock. Bleeding from multi-organs in various
      extent and coagulation disorders occurred in all those 27 cases. [Besides anti
      shock treatment, heparin was employed together with fibrinogen in 4 postpartum
      and 1 antepartum DIC patients, fibrinogen alone in 8 cases, and hysterectomy in
      11 cases. 17 patients were saved and 9 died. It is important that early diagnosis
      and much attention paid to clinical characteristics together with serial
      laboratory tests. Key management should include prompt treatment and eradication
      of predisposing factors. Quick decision spite of to terminate the pregnancy and
      even hysterectomy should be done in some risks.

PMID- 1395899
TI  - [Analysis of 18 cases of postpartum haemorrhagic shock in pregnancy with virus
      hepatitis].
AB  - In this article, 147 pregnancies with virus hepatitis admitted to our hospital
      from Dec 1987 to Jun 1991 were studied. The incidences of postpartum haemorrhage
      and haemorrhagic shock were 36.05% and 12.24% respectively, and were related to
      the clinical classification of the hepatitis, with a difference of high
      significance (P less than 0.01). Analysis of the clinical manifestations and
      results of the blood tests in 18 cases of shock suggested that the main cause of
      shock was hepatitis resulting in injury of the liver and thus absence of clotting
      factors increasing postpartum haemorrhage. Therefore, emphases on antenatal care
      by keeping the women under the monitoring by obstetrician and physician together.
      Replenishing clotting factors, rectifying clotting defects; preventing acute
      hepatitis from proceeding to severe hepatitis and pregnancy-induced hypertension
      are keys to treat antenatal hepatitis. Close intrapartum care and shortening the
      duration of labor, especially the third stage, are important to reduce postpartum
      haemorrhagic and prevent occurrence of haemorrhagic shock.

PMID- 1395900
TI  - [Perinatal fetal prognosis of essential hypertension complicating pregnancy].
AB  - Pregnancy induced hypertension (PIH) in patient of essential hypertension is a
      high risk factor for both mother and child. From July 1959 to June 1991 there
      were 52,898 deliveries after the 28th week of gestation in our hospital, among
      whom essential hypertension occurred in 2.5% and 337 cases were superimposed by
      PIH with an incidence of 25.9%. There was a perinatal fetal mortality rate of
      117.6/1000 in those 337 cases. A scoring system for perinatal fetal prognosis was
      worked out. The clinical criteria consist of: preexisting diastolic blood
      pressure, the highest diastolic pressure during pregnancy, proteinuria and the
      time of onset of PIH. A perinatal survival rate of 75.0% was obtained in those
      patients with preexisting diastolic pressure lower than 14.8 kPa (110 mmHg). A
      perinatal survival rate of more than 98.0% may be expected of those patients
      developing P I H after the 36th week of gestation. When the score is more than 8,
      the patient could usually get a living baby. If the score is less than 7, it is
      important to treat P I H effectively, terminate pregnancy at an appropriate time
      and keep the baby in the intensive care unit.

PMID- 1395901
TI  - [Effects of gentamycin on the fetal kidneys].
AB  - Gentamycin was given in 24 women during termination of mid-trimester pregnancy.
      The concentration of gentamycin in the blood of pregnant women, umbilical cords
      and in tissue of placenta, fetal kidneys were determined by fluorescence
      polarization immunoassays, and the morphological changes of fetal kidneys were
      investigated as well. The results indicated that the concentration of gentamycin
      in circulation of pregnant women was not significantly different from that of the
      umbilical cords (P greater than 0.05), but in tissue of fetal kidneys gentamycin
      concentration was remarkably higher than that in placenta (P less than 0.05). The
      following pathological findings of fetal kidneys were seen: marked congestion in
      glomeruli, cloudy swelling in the proximal tubules, reduced cilial cells and
      granular degeneration in epithelium. All these have shown that the placenta did
      not act as a barrier on gentamycin. It should be noted that while gentamycin in
      therapeutic dosage was given to pregnant women, it would be accumulated in fetal
      kidneys and caused damage.

PMID- 1395902
TI  - [Intrauterine device-induced menorrhagia and endometrial content of
      prostacyclins].
AB  - The endometrial concentration of 6-keto-PGF1 alpha and TXB2 were measured by RIA
      in women with Tcu-IUD induced menorrhagia (MBL greater than 80 ml) and in
      levonorgestrel-IUD users with oligomenorrhea or amenorrhea. Non-IUD users with
      normal menses (MBL less than 80 ml) were chosen as control. It was found that the
      Tcu-IUD group showed a significantly higher 6-keto-PGF1 alpha concentration than
      the other two groups (P less than 0.01). Conversely, the TXB2 concentration of
      levonorgestrel-IUD group was significantly higher than that of the other groups
      (P less than 0.05). As a result, the 6-keto-PGF1 alpha/TXB2 ratio was much higher
      in Tcu-IUD group (P less than 0.01). Our results indicated that the unbalance of
      PGI2/TXA2 ratio may be the direct cause of the IUD-induced menorrhagia.

PMID- 1395903
TI  - [Relation between estrogens and plasma lipid contents and their effect on
      coronary heart diseases].

PMID- 1395904
TI  - [The value of fingernail creatinine measurement in the identification of acute
      and chronic renal failure].
AB  - It is difficult to distinguish acute renal failure (ARF) clinically from chronic
      renal failure (CRF), especially in the patients who do not have medical history
      records. Since fingernail creatinine (Ncr) reflects serum creatinine (Scr) at the
      time of nail formation, it has been suggested that Ncr level might represent that
      of Scr around 4 months previously. In this study, clipped fingernail specimens
      from 60 normal individuals (Scr 85.75 +/- 3.54 mumol/L), 35 patients with CRF
      (Scr 568.41 +/- 47.74 mumol/L) and 15 patients with ARF (Scr 123.60 +/- 17.29
      mumol/L) were analyzed for creatinine by a standard alkaline picrate method. The
      results showed that Ncr level was significantly lower in the normal group (61.89
      +/- 10.25 mumol/100g fingernail) than in the CRF group (130.04 +/- 34.55
      mumol/100g fingernail) P less than 0.001. In the ARF group Ncr level (65.59 +/-
      2.5 mumol/100g fingernail) was more or less the same as that in normal controls.
      It is concluded that Ncr measurement is of clinical value in identification of
      ARF.

PMID- 1395905
TI  - [Effect of serum from IgA nephropathy patients on IL-1 production from P388 D1
      cell lines].
AB  - The study was designed to investigate IL-1 production from P388D1 cell using
      serum from 40 cases with IgA nephropathy (IgAN) as stimulative factor. It was
      found that there was a relationship between IL-1 and renal morphological change.
      The result indicated that IL-1 production by P388D1 cell was much higher in the
      presence of the serum than that in the absence (CPM: 47597 +/- 26213 vs 36567 +/-
      14377 P less than 0.05). The level of IL-1 correlated obviously to the renal
      morphologic changes (r = 0.406, P less than 0.05). It is suggested that in the
      serum of IgAN patients there are certain factors stimulating P388D1 cell to
      produce IL-1, which may contribute to the pathogenesis of IgAN.

PMID- 1395906
TI  - [Prognostic evaluation of severe viral hepatitis].
AB  - The Cox's regression model is used for analysis of registered survival data of
      severe viral hepatitis. The final regression model showed six covariates, i.e.
      grade of coma, prothrombin time, the interval between jaundice to bleeding, the
      interval between jaundice to coma, LDH, and pathological scores as well as the
      recurrence frequency were associated with survival significantly. The final model
      can be presented as a "pocket chart" by which a prognostic index (PI) for a new
      subject can easily be obtained. By a simple graph, the PI can be translated to
      estimates of the probability of surviving within a given time and the median
      survival time. A small sample of prospective study showed the predicted survival
      length did not differ from the observed survival length significantly.

PMID- 1395907
TI  - [Association between essential hypertension and immunology].
AB  - Using the immunofluorescence method, autoantibodies of serum IgG was investigated
      in 100 consecutive patients of essential hypertension with or without family
      history of hypertension. 30 healthy normotensive subjects with family history of
      hypertension and 40 healthy normotensive subjects of the same age range were also
      studied. The results showed that in the treated patients, the frequency of smooth
      muscle antibodies (SMA), antimitochondrial antibodies (AMA), antinuclear
      antibodies (ANA) and heart reactive antibodies (HRA) was higher than that in
      healthy normotensive subjects. The frequency of these antibodies was not
      associated with difference in mean arterial blood pressure, sex, and clinical
      stage and a possible genetic predisposition is suggested. The autoantibodies may
      even appear before the elevation of blood pressure in patients with essential
      hypertension. The above-mentioned results show that lack of autoimmunity may be
      one of the pathogenetic factors of essential hypertension.

PMID- 1395908
TI  - [An analysis of 21 cases of idiopathic dilatation of the pulmonary artery].
AB  - Idiopathic dilatation of the pulmonary artery (IDPA) is a disease which,
      generally speaking, does not need treatment. But a correct differential diagnosis
      is of great importance. 21 cases of IDPA were reported. The clinical data showed
      that 66.67% of the patients were asymptomatic and all the patients had normal
      respiratory and cardiovascular functions. 10% of the cases had had a history of
      more than 20 years. The results showed that IDPA was a benign anomaly and most of
      its symptoms were iatrogenic. It was usually misdiagnosed as pulmonary stenosis
      (42.86%), atrial septal defect (38.10%), pulmonary hypertension (28.57%), and so
      on. Careful chest X-ray, ECG and UCG examinations are useful for the differential
      diagnosis, but a clinical diagnosis should be based on the normal result of right
      heart catheterization.

PMID- 1395909
TI  - [Alterations of Ulex europaeus agglutinin-1 receptor in human colorectal benign
      and malignant tumors].
AB  - The distributions and alterations of UEA-1 receptor in 116 human colorectal
      mucosa, included 20 normal mucosa, 16 inflammatory and 14 hyperplastic polyps, 34
      adenomas, and 32 carcinomas, were studied with ABC technique. The results follow
      as: 1. There were positive staining of UEA-1 in proximal colon and negative in
      distal colon and rectum; 2. The frequency and intensity of UEA-1 receptor stained
      were increasing with the sequence of normal mucosa (7.7%), inflammatory polyps
      (25%), hyperplastic polyps (57.1%), adenomas (76.4%), and carcinomas (100%) in
      distal colon and rectum; 3. The staining pattern of UEA-1 in severe atypia
      adenomas was very similar to that in carcinomas and both of them were
      significantly difference from that in the other groups (P less than 0.05 or less
      than 0.01). The results suggested that UEA-1 receptor in distal colon and rectum
      may be considered as a probe studying course of malignant transformation and
      benefit to the diagnosis of carcinoma.

PMID- 1395910
TI  - [T-lineage acute lymphoblastic leukemia. Report of 23 cases].
AB  - 23 cases of T-lineage acute lymphoblastic leukemia (TALL) were identified by
      multiple monoclonal antibodies. TALL was characterized by a younger age of the
      patients (average age 28 years), strong male preponderance (M:F, 4.8: 1),
      mediastinal mass (19%), higher leucocyte count (71.4%), hepatomegaly (76.2%) and
      splenomegaly (90.5%). Of 19 cases of TALL who were subclassified according to the
      criteria for subclassification of TALL proposed by Reinherz, 10 cases expressed a
      surface antigen pattern consistent with the early thymocyte stage of TALL
      development, 8 cases were of common thymocyte stage and 1 case was of mature
      thymocyte stage. The phenotypes of TALL cells appear to be considerably
      heterogeneous. 12 of 18 patients who received chemotherapy had achieved complete
      remission (67%).

PMID- 1395911
TI  - [The effect of lovastatin in the treatment of primary hypercholesterolemia].
AB  - The effect of Lovastatin, an HMG. CoA reductase inhibitor, on serum lipids and
      apolipoproteins was studied in 40 cases of primary hypercholesterolemia in a 4
      month period of treatment. The level of serum lipids did not change significantly
      after a 35-day period of placebo treatment as compared with that of the baseline
      (P greater than 0.5). The patients then took Lovastatin with the evening meal in
      a daily dose from 20 to 80 mg for 3 months. The results were as follows:
      Lovastatin reduced significantly the mean serum level of total cholesterol (TC)
      by 31.5% (P less than 0.001), LDL-C by 39.8% (P less than 0.001), Apo-B by 27.3%
      (P less than 0.002), and the ratio TC/HDL-C by 35.9% (P less than 0.01). It also
      reduced the mean serum level of triglycerides (TG) by 22.1% (P greater than 0.05)
      and increased that of HDL-C by 6.3% (P greater than 0.2) and Apo-AI by 1.6% (P
      greater than 0.5), but without much significance. The drug was well tolerated by
      all the patients. Transient elevation of CPK was noticed in 2 patients and AKP in
      one patient. 7 patients complained of gastrointestinal discomfort. All these side
      effects did not necessitate stop of the medication. We are, therefore, of the
      opinion that Lovastatin is an effective agent for lowering the serum level of TC,
      LDL-C and Apo-B.

PMID- 1395912
TI  - [Insulin resistance and non-insulin dependent diabetes mellitus].

PMID- 1395913
TI  - [The basement membrane nephropathy].

PMID- 1395914
TI  - [The pathogenic mechanism, diagnosis and treatment of renal osteodystrophy].

PMID- 1395915
TI  - [Treatment of chronic renal failure with Oenothera beinnis L in rats with
      subtotal nephrectomy].
AB  - The effect of orally administered Oenothera Biennis L on chronic renal failure
      was studied in the partially nephrectomized rats. As compared with the control
      groups, the group treated with Oenothera showed the following features. 1) Urine
      protein excretion was reduced; 2) Level of serum cholesterol decreased; 3) Scr
      maintained the same level as before treatment; 4) Level of PGE1 and PGE2
      increased both in renal cortex and medulla; 5) 6-keto PGF1 alpha increased in
      cortex; 6) Increased TXB2 production was only observed 4 weeks after nephrectomy;
      7) Glomerular lesions were more severe in control group. It is concluded that
      Oenothera Biennis L has beneficial effect on the remnant kidney and may be useful
      as a kind of conservative treatment for chronic renal failure.

PMID- 1395916
TI  - [Degree of cellular proliferation in the first-time bone marrow smear and its
      significance in the diagnosis of aplastic anemia].
AB  - According to the cellularity in the first bone marrow aspirate, 541 cases of
      aplastic anemia (AA) diagnosed in the Peking Union Medical College Hospital were
      divided into two groups--hypoplastic and hyperplastic. Comparison of the
      transformation, remission and long-term survival rates in the two groups showed
      the following results. (1) Transformation: In the hypoplastic group, 60% of the
      cases maintained the original degree of proliferation, 34% was transformed to
      hyperplastic, 3% had repeated transformation and 3% became leukemic. In the
      hyperplastic group, 44% maintained the original degree of proliferation, 44% was
      transformed to hypoplastic, 9.3% had repeated transformation and 2.7% became
      leukemic. (2) Remission rate: The total remission rate was 15.9% in the
      hypoplastic and 14.6% in the hyperplastic group. (3) Long-term survival rate: The
      1-, 5- and 10-year survival rates were 70.43%, 57.66% and 51.51% in the
      hypoplastic group, while they were 86.7%, 71.24% and 63.34% respectively in the
      hyperplastic with statistical significance (P less than 0.01). It is emphasized
      that AA can not be ruled out if there is hyperplasia in the bone marrow smear
      taken for the first time or in several smears taken from the same site. Smears
      taken periodically from different sites are essential for correct diagnosis.

PMID- 1395917
TI  - [The advances in immunological research of Helicobacter pylori].

PMID- 1395918
TI  - [Clinical investigation of vitamin A deficiency and endotoxemia in patients with
      liver cirrhosis].
AB  - Eighty four patients with liver cirrhosis were studied and their plasma levels of
      vitamin A, fibronectin and endotoxin were assayed. Various degrees of vitamin A
      deficiency were found in 79% of the patients, but no deficiency in vitamin A
      caused the rise in plasma fibronectin. The incidence of endotoxemia and secondary
      infections in vitamin A deficient patients (82%, 31%) was significantly higher
      than that in normal vitamin A group (P less than 0.01). In 62% of the patients,
      vitamin A deficiency and endotoxemia existed simultaneously. For patients in whom
      vitamin A deficiency and fibronectin decrease coexisted, the incidence of
      endotoxemia was 93%. The findings demonstrated that vitamin A deficiency is an
      important cause of complicating endotoxemia and secondary infection in cirrhotic
      patients. Further efforts should be made to evaluate the clinical value of
      combined assay of vitamin A and fibronectin in estimating the liver function and
      prognosis of the patients.

PMID- 1395919
TI  - [Studies on plasma beta-thromboglobulin, thromboxane A2, prostaglandin I2
      concentration and platelet count in liver diseases].
AB  - We measured blood platelet count and plasma beta-thromboglobulin concentration in
      67 patients with acute or chronic liver diseases. Plasma TXB2 and 6-keto-PGF1a
      concentration were also measured in these patients. The results showed that blood
      platelet count of less than 100 x 10(9)/L was found in 14% of the patients with
      acute hepatitis, 23% with chronic hepatitis, 67% with hepatic cirrhosis but
      without splenectomy and 40% with primary liver carcinoma. Platelet count is
      lowest in patients with hepatic cirrhosis without splenectomy but normal in
      patients with hepatic cirrhosis after splenectomy. Plasma beta-TG concentration
      increased in patients with acute or chronic liver diseases. A negative
      correlation was found between beta-TG concentration and platelet count in chronic
      liver diseases. It is suggested that platelet is in activated state in vivo and
      this may be one of the important reasons for both decrease of platelet count and
      impairment of platelet function. Plasma TXB2 concentration increased in chronic
      liver diseases, while plasma 6-keto-PGF1a concentration decreased. The balance
      between TXA2 and PGI2 is upset; this may be an important mechanism for activation
      of platelets in vivo.

PMID- 1395920
TI  - [Evaluation of serum SC6 antigen using immunoradiometric assay for diagnosis of
      pancreatic cancer].
AB  - A solid-phase immunoradiometric sandwich assay for SC6 antigen was defined by a
      monoclonal antibody (SC6). The concentration of SC6 antigen in samples was
      determined by reference to a standard curve. The average intra- and interassay CV
      were 5.4% and 8.7% respectively. This antibody was found at low concentration in
      serum from 33 healthy individuals and the cutoff of normal upper limit of SC6
      antigen was 41 U/ml. The level of serum SC6 antigen was assayed in 41 patients
      with pancreatic cancer, 95 with non-pancreatic carcinomas, and 48 with
      nonmalignant diseases. Frequency of elevated SC6 antigen level was highest in
      patients with gastrointestinal cancer, especially pancreatic cancer. The
      sensitivity and specificity were 70.7% and 84.3% for pancreatic cancer. The level
      in most cases of benign diseases was within upper normal limit. The results show
      that detection of SC6 antigen is valuable in the diagnosis of pancreatic cancer.
      It may be of help for detecting pancreatic cancer in its early stage.

PMID- 1395921
TI  - [Sclerotherapy of gastric varices].
AB  - 160 patients, 128 males, 32 females, with portal hypertension were admitted into
      our department for sclerotherapy from May 1987 to August 1990. Gastric fundus
      could be observed clearly in 145 of these patients who were examined with
      endoscope. Gastric varices were found in 105 of the 145 patients. Sclerotherapy
      of gastric varices were carried out in 47 of the 105 patients by intravenous
      injection with the method of lesser injection points and larger dosage. The
      results showed that a satisfactory effect was obtained with a rate of immediate
      stoppage of bleeding by 95.7%; and a rate of disappearance of gastric varices by
      95.3%. The rate of recurrent bleeding was 7.9%. In addition, the occurrence rate,
      the severity, the manifestations under endoscopy and the classification of
      gastric varices as well as the indication, and complications of sclerotherapy of
      gastric varices were discussed in detail.

PMID- 1395922
TI  - [Studies on second-degree atrioventricular block during atrial fibrillation].
AB  - The degree of AV block after cardioversion in 80 episodes of atrial fibrillation
      in 61 patients who suffered from atrial fibrillation associated with second
      degree AV block was observed. Only in 34 of the 80 episodes the electrocardiogram
      showed first-degree AV block. The remaining 46 had normal AV conduction. No
      second-degree block was found. It demonstrates that second-degree AV block during
      atrial fibrillation is not identical with that in sinus rhythm.

PMID- 1395923
TI  - [Treatment of various types of acute leukemia in adult. An analysis of 98 cases.
      The Leukemia Cooperation Group of Beijing City].
AB  - 47 cases of acute non-lymphocytic leukemia (ANLL) were treated with daunorubicin,
      cytosine arabinoside. Complete remission (CR) rate was 61.7%. 6 cases of ANLL M3
      type were treated with trans-retinoic acid and all had CR. 45 cases of acute
      lymphocytic leukemia (ALL) were treated with vincristine, daunorubicin,
      cyclophosphamide, prednisone with a CR rate of 88.9%. The preliminary result of
      consolidation or intensive therapy after CR was reported. The toxic and side
      effects of all kinds of treatment program were described.

PMID- 1395924
TI  - [The expression of C-myc oncogene in leukemia and its relationship to clinical
      symptoms].
AB  - The expression of C-myc proto-oncogene were studied at the levels of protein in
      bone marrow cells obtained from patients with AML and CML. It was found that the
      expression of C-myc in florid AML and during blast phase of CML were much higher
      than that in remission of AML and in chronic phase of CML. In 7 cases of AML
      diagnosed for the first time, 2 cases with high C-myc expression had no remission
      after 3-6 months, while 5 with rare C-myc expression had remission after 3-6
      months. This results suggest that the expression of C-myc proto-oncogene are
      possibly sensitive indicator of the prognosis of leukemia.

PMID- 1395925
TI  - [A regimen of DATV in the treatment of acute nonlymphocytic leukemia with high
      complete remission rate].
AB  - Thirty-eight adults including 24 males and 14 females with acute nonlymphocytic
      leukemia were treated with DATV (Daunorubicin, Cytarabine, 6-thioguaninum,
      Vincristine) regimen from December 1987 to May 1991. The median age was 31 years
      old (range 13-54). The DATV regimen consisted of DNR 60 mg/day IV for 3 days; Ara
      C 100 mg by continuous infusion every 12 hours for 7 days; 6-TG 150 mg PO for 7
      days and VCR 2mg IV on day 1. RESULTS: Complete remission (CR) was achieved in
      thirty-three of 38 patients after 1-2 courses (mean 1.3) with CR rates 86.8%.
      Five patients had no response to the regimen. Twenty-four of 33 patients who
      achieved CR are still in CR for 1-41 months with a median follow-up of 10 months.

PMID- 1395926
TI  - [A clinicopathological study of leukemic kidney].
AB  - A clinicopathological study of leukemic kidney was carried out by observing the
      changes of the kidney in 104 autopsied cases of leukemia. The main changes of the
      leukemic kidney were increase of renal weight, calcinosis of renal tubules,
      interstitial leukemic cell infiltration, intravascular stasis and renal bleeding.
      Calcinosis intravascular stasis, renal bleeding as well as hyperuricemia may lead
      to abnormal urinary findings. The presence and severity of interstitial
      infiltration have no obvious relation with the level of blood urea nitrogen,
      creatinine and muric acid as well as the abnormal change of the urine. However,
      the presence of intravascular stasis by leukemic cells are correlated with the
      disturbance of renal function.

PMID- 1395927
TI  - [Magnetic resonance imaging in diagnosing hypertrophic cardiomyopathy: an
      analysis of 10 cases].
AB  - Ten patients with hypertrophic cardiomyopathy (HCM) were examined with ECG-gated
      magnetic resonance imaging (MRI), one of whom was a child. MRI shows deformities
      of left ventricular cavity in all 10 patients, shapes of majority being long and
      narrow. Interventricular septums (IVS) were identically thickened in 5 patients,
      middle areas of IVS were thickened in 3 patients, local area of IVS was thickened
      in ball-shape in 1 patient, the apex was thickened in 1 patient. The ratio of
      thickened of IVS between in systole and diastole was less 1.08 in 5 patients and
      equal to 1.0 in 4 patients. The ratio of thickness of thickened left ventricular
      posterior wall between in systole and diastole was less than 1.25 in 7 patients.
      Ratios were respectively 1.25 and 1.53 in a child, obviously higher than those of
      adults. Left ventricular outflow tract was narrow in 1 patient. Left atria were
      enlarged in 7 patients. left ventricular diastolic function was damaged in 8
      patients and systolic function was damaged in 1 patient. Signal intensity in IVS
      was not identical in 6 patients, of whom 3 patients suggests degenerate degree of
      myocardium in comparison with histology of myocardium. Proximal ends of coronary
      arteries were clear in 4 patients and didn't show narrow. All 10 patients were
      examined with UCG, 9 patients with ECT, 3 patients with ventricular angiography.
      All results coincide with features of HCM.

PMID- 1395928
TI  - [The interaction of some active and immunological factors in blood in the
      development of chronic cor pulmonale].
AB  - Fourteen experimental indices were determined in 26 patients of chronic cor
      pulmonale due to COPD and in 32 healthy nonsmokers. It was found that elastase,
      TXB2, ATII, 5-HT, IgE, CTC and Ach were significantly higher whereas 6-keto -PGF1
      alpha, C4 and cAMP lower in the blood from the patients. The roles played by
      these factors in the development of chronic cor pulmonale were discussed.

PMID- 1395929
TI  - [Thin membrane nephropathy (TMN). Analysis of 8 cases].
AB  - This present study first reported 8 cases of Thin membrane nephropathy (TMN) in
      China. Most patients had persistent microscopic hematuria, who could be
      accompanied with mild proteinuria or macroscopic hematuria. The contrast
      microscopy showed glomerular hematuria in the majority of the cases. Some
      patients (25%, 2 cases) had familial hematuric histories, suggesting this disease
      may be associated with heredity. All the patients had normal renal function at
      following-up period (average 2.9 years), this result showed this disease was
      benign glomerular disease. LM showed pathological change is mild, IF was
      negative, diffuse thin GBM was outstanding change by EM. The thickness of TMN was
      265 +/- 39 nm, the thickness of IgA GN and normal control were separately 383 +/-
      32 nm and 398 +/- 34 nm, the thickness of TMN was significantly thinner than IgA
      GN and normal control (P less than 0.01). This study showed ultrastructural
      observation of glomeruli by EM was necessary to diagnose this disease.

PMID- 1395930
TI  - Tyrosine phosphatases and their possible interplay with tyrosine kinases.
AB  - Protein tyrosine phosphatases represent a new family of intracellular and
      receptor-linked enzymes. They are totally specific toward tyrosyl residues in
      proteins, and, with specific activities 10-1000-fold greater than those of the
      protein tyrosine kinases, they can be expected to tightly control the level of
      phosphotyrosine within the cell. Most transmembrane forms contain two conserved
      intracellular catalytic domains, as displayed by the leukocyte common antigen
      CD45, but highly variable external segments. Some are related to the neuronal
      cell adhesion molecules (NCAMs) or fasciclin II and others contain fibronectin
      III repeats; this suggests that these enzymes might be involved in cell-cell
      interaction. The intercellular enzymes appear to contain a highly conserved
      catalytic core linked to a regulatory segment. Deletion of the regulatory domain
      alters both substrate specificity and cellular localization. Likewise,
      overexpression of the full-length and truncated enzymes affects cell cycle
      progression and actin filament stability, respectively. The interplay between
      tyrosine kinases and phosphatases is considered. A hypothesis is presented
      suggesting that in some systems phosphatases might act synergistically with the
      kinases and elicit a physiological response, irrespective of the state of
      phosphorylation of the target protein.

PMID- 1395931
TI  - Calmodulin and protein kinase C cross-talk: the MARCKS protein is an actin
      filament and plasma membrane cross-linking protein regulated by protein kinase C
      phosphorylation and by calmodulin.
AB  - The myristoylated, alanine-rich C kinase (PKC) substrate (MARCKS) is a major,
      specific substrate of PKC that is phosphorylated during macrophage and neutrophil
      activation, growth factor-dependent mitogenesis and neurosecretion. MARCKS is
      also a calmodulin-binding protein and binding of calmodulin inhibits
      phosphorylation of the protein by PKC. Several recent observations from our
      laboratories suggest a role for MARCKS in cellular morphology and motility.
      First, in macrophages MARCKS is located at points of cellular adherence where
      actin filaments insert at the plasma membrane and is released to the cytoplasm
      upon activation of PKC. Second, during neutrophil chemotaxis MARCKS undergoes a
      cycle of release from, and reassociation with, the plasma membrane. Third, in
      vitro, MARCKS is an F-actin cross-linking protein whose activity is inhibited by
      PKC-mediated phosphorylation and by binding to calmodulin. MARCKS therefore
      appears to be a regulated cross-bridge between actin and the plasma membrane.
      Regulation of the plasma membrane-binding and actin-binding properties of MARCKS
      represents a convergence of the PKC and calmodulin signal transduction pathways
      in the control of actin cytoskeleton-plasma membrane interactions.

PMID- 1395932
TI  - T lymphocyte activation signals.
AB  - Activation of T lymphocytes results in immediate biochemical changes including
      increases in intracellular calcium levels, activation of protein kinase C (PKC)
      and changes in tyrosine phosphorylation. In T cells recent studies have indicated
      that activation of the guanine nucleotide-binding proteins p21ras is mediated by
      PKC, which suggests that the p21ras proteins may regulate intracellular
      signalling events downstream of PKC. The p21ras proteins can be activated in T
      cells by signals generated by triggering of the T cell antigen receptor (TCR),
      the CD2 antigen and the interleukin 2 receptor. Experiments using a PKC
      pseudosubstrate inhibitor indicate that PKC does not mediate TCR-induced
      activation of p21ras. These results imply that an alternative signal transduction
      pathway not involving PKC can regulate the activity of p21ras proteins in T
      cells.

PMID- 1395933
TI  - Growth factor phosphorylation of PLC-gamma 1.
AB  - The hydrolysis of phosphatidylinositol 4,5-bisphosphate has a central role in
      many signalling pathways. One of the phospholipase C (PLC) isozymes that mediates
      this reaction is a direct substrate for the tyrosine kinase activity of several
      growth factor receptors. Growth factors elicit increases in both the
      phosphoserine and the phosphotyrosine content of the PLC-gamma 1 isozyme. PLC
      gamma 1 contains three tyrosine phosphorylation sites, which have been identified
      as residues 771, 783 and 1254. Phosphorylation of tyrosine residues is sufficient
      to increase the catalytic activity of PLC-gamma 1, though other proteins may
      modulate this activation. However, the role of growth factor-enhanced
      phosphorylation of serine residues on PLC-gamma 1 remains obscure. In vitro
      studies of PLC-gamma 1, recovered from growth factor-treated cells, indicate that
      activation by tyrosine phosphorylation is not due to increased sensitivity to
      Ca2+, a required co-factor, but is reflected in altered kinetic constants, i.e.
      V(max) and, to a lesser extent, Km.

PMID- 1395934
TI  - Protein tyrosine kinases belonging to the src family.
AB  - There are nine non-receptor-type protein tyrosine kinases that show a high level
      of similarity in their primary structures and in the structures of their
      functional domains. Together, they are called the src family. They seem to have
      common sites specific for oncogenic activation. Recent findings suggest that the
      kinases are closely associated with cell surface molecules and that they mediate
      extracellular signals through the activation of their tyrosine kinase activity.
      They appear to act more on the differentiated phenotype than in haemopoietic cell
      proliferation. Possible functions of the products of the lck, fyn, lyn and fgr
      genes in lymphocytes and monocytes are discussed.

PMID- 1395935
TI  - The signal-induced phospholipid degradation cascade and protein kinase C
      activation.
AB  - Acting in synergy with diacylglycerol, unsaturated free fatty acids such as
      arachidonic, oleic, linoleic, linolenic and docosahexaenoic acids dramatically
      activate some members of the protein kinase C family at the basal level of Ca2+
      concentration. It is plausible that phospholipase C and phospholipase A2, and
      possibly phospholipase D as well, are involved in the activation of protein
      kinase C. Presumably, this enzyme activation is integrated into the signal
      induced membrane phospholipid degradation cascade, prolonging the activation of
      protein kinase C. The sustained activity of this enzyme appears to be of
      importance for long-term cellular responses such as development of neuronal
      plasticity and gene activation.

PMID- 1395936
TI  - The acetylcholine receptor: a model of an allosteric membrane protein mediating
      intercellular communication.
AB  - Over the past 20 years the nicotinic acetylcholine receptor has become the
      prototype of a superfamily of ligand-gated ion channels. As a single
      macromolecular entity of M(r) about 300,000, the receptor protein mediates,
      altogether, the activation and the desensitization of the associated ion channel
      and the regulation of these processes by extracellular and intracellular signals.
      The notion is discussed that the acetylcholine receptor is a membrane-bound
      allosteric protein which possesses several categories of specific sites for
      neurotransmitters and for regulatory ligands, and undergoes conformational
      transitions which link these diverse sites together. At this elementary molecular
      level, interactions between signalling pathways may be mediated by membrane-bound
      allosteric receptors and/or by other categories of cytoplasmic allosteric
      proteins.

PMID- 1395937
TI  - [Magnetic stimulation motor evoked potential in multiple sclerosis. Comparison
      with visual evoked potentials, brain stem auditory evoked potentials and
      somatosensory evoked potentials].
AB  - This study consists of 45 patients with clinically definite MS, laboratory
      supported definite MS and clinically probable MS. We compared MEP results with
      other multimodal evoked potentials (VEP, BAEP and SEP). The abnormal rate of MEP
      was 87.6%, which was the highest. Abnormal MEP showed prolonged central motor
      conduction time (CMCT), consistent with pathological change of the demyelination.
      There was a evident correlation between the abnormal MEP and VEP, which is
      consistent with the most common MS (Devic Syndrome) in our country.

PMID- 1395938
TI  - [Diagnostic value of suspect epilepsy by means of 24 hour of ambulatory
      electroencephalogram].
AB  - 106 cases of suspect epilepsy random observed by means of 24 hr tape recording of
      AEEG were given in this paper. Among them 57 cases. (accounting for 53.77%) are
      lightly abnormal including 42 cases (accounting for 39.62%) recorded as epilepsy
      burst. Comparing with EEG: Among 93 cases 25 cases as lightly abnormal by EEG
      (accounting for 26.88%), 52 cases recorded as lightly abnormal by AEEG
      (accounting for 55.91%) (P less than 0.005); arising rate of epilepsy burst 11
      cases were recorded by EEG (accounting for 11.82%), 41 cases by AEEG (accounting
      for 44.01%) (P less than 0.005). The record of epilepsy burst patients monitored
      showed that positive rates of transient consciousness loss (8/15, 53.33%) and
      convulsions (9/19, 47.39%) are the highest. Abnormal burst time by AEEG is during
      sleeping (54 cases observed accounting for 77.14%) with positive rate highest at
      the same time, most accorded in the front temporal area (29/92, 31.52%). The
      author therefore, suppose that AEEG is more accurate to find abnormal bast wave
      or epilepsy burst wave than EEG because of superior condition in recording time
      to EEG and could offer more objective diagnosis reference for suspect epilepsy
      patients who are difficult to be checked clinically because of low positive rate
      of EEG.

PMID- 1395939
TI  - [Benign focal epilepsy of childhood (BFEC)].
AB  - Thirty cases of benign focal epilepsy of childhood were reported. The seizures
      were partial or generalized motor ones in all cases. One patient had episodes of
      visual hallucination with motor seizures. No objective examination has
      demonstrated cerebral lesions in all cases. The most characteristic in the
      present study was that the attacks were in relation to the sleep in 90% of cases,
      56.7% of all patients had nocturnal seizure only. The characteristic EEG patterns
      were the spike or sharp discharges in Rolandic area in 29 cases, and occipital
      sharps or sharp wave complexes in one patient on normal background activities.
      The discharge rate of Rolandic spikes or sharps were significantly higher during
      sleep than during the awake stage, and 12 cases had Rolandic discharges only
      during sleep. Sleep EEG recordings is suggested when children were suspected of
      having such kind of seizure type but having a normal EEG pattern when awake.
      Brief induced sleep is usually adequate.

PMID- 1395940
TI  - [A study of alexia in Chinese language].
AB  - Twenty-five cases of alexia were examined with Chinese Alexia Test which was
      devised according to the features of Chinese ideogram. The result of our study
      showed that alexia in Chinese ideographic language differs from alexia in western
      phonographic languages. It has its own characteristics and is manifested as
      following patterns: difficulty in reading aloud, dissociation of appearance and
      meaning of character, alexia of combinative character, alexia of associative
      compounds, alexia of abstract word, visual paralexia, surface alexia, deep
      alexis, phenomenon of word completion (formation of words by addition of another
      character), substitution with neologisms, perseveration in alexia, character and
      word alexia, syntactic alexia, and total alexia. Twenty-five cases of alexia were
      classified according to Benson's classification of alexia as anterior, central,
      subcortical aphasic and total alexis. One case with proterior alexia was briefly
      reviewed. The main differential points of various alexia in Chinese language were
      suggested.

PMID- 1395941
TI  - [Acute herpes simplex encephalitis treated with acyclovir. Report of 5 cases].
AB  - 5 cases of acute herpes simplex encephalitis were verified by specific IgG
      antibodies in cerebrospinal fluid and serum among 31 cases with 'sporadic
      encephalitis' within one year. All were treated with acyclovir, 4 with remarkable
      response--2 cured and 2 significantly recovered, except one died due to delayed
      specific treatment. The dosage of acyclovir used by the author was 5mg/kg/12-24
      hours.

PMID- 1395942
TI  - [HLA and acetylcholine receptor antibody in patients with myasthenia gravis].
AB  - Human leucocyte antigen (HLA) and acetylcholine receptor antibody (AchRab) titer
      in the serum assayed were in 106 and 100 patients with myasthenia gravis (MG),
      respectively. 93 of the total patients had both HLA and AchRab assays. There is a
      strong association between HLA Bw46, Cx46 antigens and the patients with MG. The
      AchRab level in the patients with positive Bw46, Cx46 antigen is significantly
      lower than that of the patients with negative Bw46 Cx46 antigen. The geometric
      means (G) of AchRab were 2.99 and 4.74, respectively, P less than 0.05. From our
      study, We think the patients with MG could be divided into two groups, according
      to the clinical presentation, the AchRab level and the association with HLA Bw46,
      Cx46 antigens. The first group is that who present ocular muscular myasthenia,
      childhood or adolescence onset, lower level of AchRab titer and strong
      association with HLA Bw46 and Cx46. The second one is that who have general
      muscular myasthenia, adult onset, higher level of AchRab titer and no association
      with Bw46 and Cx46.

PMID- 1395943
TI  - [A preliminary study of cerebrospinal fluid cytology in aged patients with
      dementia].
AB  - 31 cases of dementia of the aged were studied with the method of CSF cytology. Of
      the 31 cases, 14 were of Alzheimer dementia (AD), 17 multi-infarct dementia
      (MID), and 25 aged subjects were studied as control. The results showed that the
      number of lymphocytes in the CSF in AD group was obviously higher than that in
      MID group. The number of monocyte--macrophages was decreased in both two studied
      groups in comparing with that of the control group. We didn't find macrophages in
      AD group. The number of neutrophils in the CSF was high in both observed groups,
      and more markedly in AD group. The significance and specialty of the results need
      further study.

PMID- 1395944
TI  - [Study of 315 pedigrees with idiopathic mental retardation by segregation
      analysis].
AB  - 315 pedigrees with idiopathic mental retardation (MR) have been studied by
      complex segregation analysis. The results show that there is no major gene effect
      in the mild MR, but in the medium and severe MR there are major gene effect. The
      pattern of inheritance of the medium MR may be codominant and the penetrance of
      the dominant gene is 0.91. The mode of inheritance of the severe MR may be
      recessive and probably without sporadic cases.

PMID- 1395945
TI  - [Neuropsychological and behavioral status of children with congenital heart
      diseases].
AB  - 39 children patients with acyanoid ventricular septal defect or atrial septal
      defect who received cardiac operation, were compared with a age and sex matched
      normal control group on a battery of neuro-psychological tests, intelligence
      tests and children behavioral checklist. Subject were examined prior to cardiac
      operation and 6 months after the operation. 12 of 39 children received
      postoperation tests. Among them, 8 were in younger children group (5 to 8 years
      old), 4 were in elder children group (9 to 14 years old). Results are: 1.
      Neuropsychological development status: (1) Full IQ(FIQ), Verbal IQ(VIQ), and
      Performance IQ(PIQ) of the group with heart diseases were lower than those of
      normal controls, and there were significant differences. (2) In cardiac patients
      significant impairments were found on some scores of the Halstead-Reitan Battery
      in comparison with the normal control group. These findings imply that patients
      before cardiac operation had generalized impairments in neuropsychological
      function. (3) Significantly more behavioral problems especially the so called
      externalizing and internalizing behavioral problems, were found in cardiac
      patients than the controls. 2. Comparison of the pre and post operative scores
      were made: Both groups (cardiac patients and controls) showed significant
      improvements in VIQ, PIQ, FIQ and most of H-R subtests scores 6 months later. But
      the improvements following surgery were attributed to practice effects.

PMID- 1395946
TI  - [A comparative study of the serum levels of thyrotropin in depressed patients and
      normal subjects].
AB  - Serum TSH levels were measured by radioimmunoassay in 85 affective disorders and
      41 healthy control persons. The results showed that the serum TSH levels of the
      patient group were significantly lower than the normal control's. TSH levels
      among different clinical episodes, however, have no significant difference.
      Furthermore, There were not a marked difference of TSH levels in age, sex and
      used antipsychotics, antidepressants, lithium or not. The results suggested that
      further investigations were needed to understand thyroid function state.

PMID- 1395947
TI  - [Level of psychosomatic health influencing by the factors of life events and
      personality trait in 1,423 armymen].
AB  - A survey of the level of psychosomatic health influencing by life events and
      personality trait in 1423 armymen was presented in this paper. The results
      demonstrated that the level of psychosomatic health was relatively poor in old
      soldier group, especially more distinct seen in over than 3-year military service
      group. The psychosomatic health state of private soldier group was relative
      better. The main factors influencing over the psychosomatic health state were the
      frequency of the negative life events, negative life change units (LCU) within
      one year prior to survey, personality trait and length of military service. The
      subordinate factors were the frequency of the positive life events and LCU within
      one year prior to survey, age and family of mental disorders.

PMID- 1395948
TI  - [Epidemiological study of children's mental health in Fuzhou].
AB  - This epidemiological survey of mental health's conditions among 1,428 children
      below the age of 14 in an urban and rural area with a population of 398,674 was
      carried out with the standardized methods and diagnostic criteria, the result
      shows that the total incidence of abnormal mental health's conditions is
      70.03/1000. Through a statistical deal, the result shows that the weights of
      these infants are slight, that they can only recognize their parents slowly, that
      their parents are in low educated levels. That the emotion between their parents
      is always not so harmonious, and that their parents always treat their children
      with different attitudes. In short, all these factors are in close connection
      with the incidence of abnormal mental health of these children.

PMID- 1395949
TI  - [HTLV-I associated myelopathy].

PMID- 1395950
TI  - [Studies on the scope of labour contraindication for female workers].
AB  - According to the physiological characteristics of women and the specific effects
      of occupational hazards on the female, the medical basis of the scope of labour
      contraindications for female workers was discussed. The condition of female
      workers engaged in harmful works was investigated at 263 factories in 11 cities.
      In addition, an evaluation of the adverse effects on women's reproductive
      function of 28 harmful occupational factors was carried out. On this basis the
      range of labour contraindication for female workers was proposed.

PMID- 1395951
TI  - [Measurement of superoxide dismutase activity in the blood of radiation workers].
AB  - In this study, we measured the superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase GPX) activities in the peripheral blood of radiation
      workers (111 cases) and the controls (108 cases), also analyzed chromosome
      aberrations in blood lymphocytes by means of G-banding technique. The chromosome
      deletions were not found in the controls. There were 7 cases chromosome deletions
      found by G-banding in 111 cases of radiation workers, their SOD activities were
      markedly lower than those in the controls (P less than 0.05). SOD and CAT
      activities in the other 104 cases of radiation workers were significantly higher
      than those in the controls (P less than 0.01). But there was no difference of GPX
      activity between the radiation workers and the controls. However, increase of SOD
      activity mainly occurred in radiation workers who were exposed to radiation over
      0.0177 +/- 0.0032 Gy. The possible mechanism of this phenomenon was discussed.

PMID- 1395952
TI  - [Sampling of expiratory benzene and gas chromatography].
AB  - The method of sampling alveolar air and gas chromatography of trace benzene is
      reported. The lowest detectable concentration of benzene is 7.9 x 10(-4) mg/m3 in
      100 ml volume. Method parameters are r = 0.999.9, mean recovery 95.14% and mean
      relative deviation (CV) 4.94%. 42 non-occupational and 48 occupational workers
      who exposed to benzene were studied by this method. The concentrations of exhaled
      benzene are respectively 0.016 +/- 0.011, 0.138 +/- 0.093 (before workshift) and
      10.17 +/- 4.11 mg/m3 (after the end of the workshift). The results showed that
      this method is a simplified method for sampling alveolar air and analysis.
      Besides for expiratory benzene, this method can be also applied to monitoring of
      atmospheric trace benzene.

PMID- 1395953
TI  - [Experimental study on dose effect relationships between ultraviolet rays and its
      early impairment].
AB  - An experimental study on dose time effect relationships was carried out on mice
      by using epidermic cell DNA damage, skin immune suppression and histological
      change as indicators. The results showed that when animal exposed to a daily dose
      of 0.12 MED of Ultraviolet rays for 12 weeks, no obvious change was found. It
      suggested that this dose level would be safe. But at 0.5 MED dose level, increase
      in UDS repair, decrease in number of skin Langerhans cells and the presence of
      skin-aging occurred, showing that 0.5 MED dosage had a slow damaging effect. With
      regard to the effect of time, the longer the exposure the stronger the effects,
      but the early impairment was mainly related to the daily dose, rather than to the
      total dose.

PMID- 1395954
TI  - [The multivariate canonical discriminant analysis between physical growth and
      nutrition status of children and youth].
AB  - This paper is on studying the relationship between physical growth and nutrition
      status of children and youth by using multivariate canonical discriminant
      analysis. 3,790 boys and girls of 7-19 yrs of age were classified into four
      groups according to the height-for-weight method. Then, by using seven physical
      measures as predict variables, canonical discriminant functions were set up for
      boys and girls respectively. The backward substitutional test showed that the
      coincidence ate was quite high, 90.90% for boys and 92.47% for girls
      respectively. The susceptibility of various physical measures in reflecting
      children's nutrition status was analysed, and the practical use of these
      discriminant functions was discussed.

PMID- 1395955
TI  - [A study on the relationships among plasma testosterone, sex development and
      serum zinc in normal boys aged 10-15].
AB  - The plasma testosterone and serum zinc of 123 normal boys, aged 10-15 were
      measured and compared with their sex development in stages. The results showed:
      concentrations of plasma testosterone, serum zinc and other indicators of sex
      development increased along with age and stage of sex development. There was
      positive correlation between levels of plasma testosterone and serum zinc and the
      development of testicles and penis.

PMID- 1395956
TI  - [Chinese strategies for hepatitis B virus markers screening in hepatitis B
      vaccination based on cost-effectiveness analysis].
AB  - By means of decision tree model and cost-effectiveness analysis 15 kinds of
      programmes which may be used for hepatitis B virus markers screening in
      vaccination were evaluated. The results showed that the most cost-effective
      alternative was to identify the negatives for anti-HBc again after testing for
      anti-HBs and vaccinating all test negatives. That is to say it must not be
      adopted for persons to be tested for HBsAg, anti-HBs and anti-HBc before being
      vaccinated. Sensitivity and threshold analysis were also done to determine the
      effects of changes in the costs of vaccine and screening tests.

PMID- 1395957
TI  - [The effect of methylmercury on testicular function of mice].
AB  - The results showed that the amount of methylmercury (MeHg) in testis correlated
      positively with exposure doses (r = 0.99 P less than 0.01). MeHg affected the
      process of spermatogenesis, causing decrease of sperm count and increase of sperm
      abnormalities. Pathological and electron microscopic examinations indicated that
      spermatogenic cells were damaged by MeHg especially spermatogonium and
      spermatocyte. Changes of microstructure were mainly degeneration, fragmentation
      vacuolation and large lipid drop formation of spermatogenic cells. The acrosome
      of many spermatids showed obvious changes. Destruction of blood-testis barrier
      was observed in 1/10 LD50 group. Quantitative histological examination also
      confirmed that MeHg resulted in lessening of its area of seminiferous tubules and
      reduction of germ cells. The contents of testosterone were not decreased in the
      treated groups other than the 1/10 LD50 group.

PMID- 1395958
TI  - [The aflatoxins and liver cancer in Guangxi, China].
AB  - The AFB1 intake and the AFM1 excretion of 81 households in 10 villages, Guanxi
      were investigated using the ELISA method. The results showed that there was
      positive correlation between PLC mortality and AFB1 intake from corn and peanut
      oil, but not from rice. The results of stepwise regression showed that main
      factors were AFB1 intake of males, AFM1 excretion of females and consumption of
      corn. The results showed that aflatoxins were correlated with mortality rates of
      liver cancer. Further investigation needs to be carried out in case-control and
      cohort studies.

PMID- 1395959
TI  - [Blockage of glyrrhiza uralensis and chelidonium majus in MNNG induced cancer and
      mutagenesis].
AB  - Glyrrhiza Uralensis (GU) and Chelidonium Majus (CM) are two kinds of Chinese
      herbal medicine. GU and CM not only exert much stronger effects in blocking
      mutagenesis due to strains of Salmonella typhimurium (TA 97, TA 98, TA 100, TA
      102), but also have different degrees of obstructing mutagenesis induced by
      Furapromidum (F30066), Zhengdingmycin Hydrochloride (DM), N-methyl-N1-nitro-N
      nitrosoguanidine (MNNG) and Methyl-methanesulfonate (MMS). The blockage effect of
      GU and CM obviously depends on the doses used. GU and CM could also impede the
      occurrence of stomach cancer induced by MNNG, and the impeding rate is about
      sixty percent.

PMID- 1395960
TI  - [Relationship between high sodium diet and hypertension and results of
      intervention in high sodium diet population].
AB  - An epidemiologic survey of the morbidity and mortality rates of hypertension and
      related disease was carried out in a population of 9,570 composed of salt workers
      and building workers. The survey rate was 96.59%. The age-standardized morbidity
      rate of hypertension in the salt workers was 27.88%, while that in the building
      workers was 8.5%. Na concentration and Na/K rate in 8 hrs' nighttime urine in
      salt workers were significantly higher than in building workers (P less than
      0.001). Results of intervention of salt intake at the level of 10 g/person/day in
      285 cases of hypertensives for 3 months showed that mean levels of systolic
      pressure and diastolic pressure decreased by about 3.1 kPa (P less than 0.001)
      and 1.9 kPa (P less than 0.01) respectively; the mean body weight decreased by
      about 2.2 kg; Na concentration in 8 hrs' nighttime urine and its Na/K radio
      significantly decreased (P less than 0.001), while K Concentration increased. The
      situation of high level of Na and low level of K in human body was obvious on
      long-term high sodium diet population. Intervention of salt intake had
      considerable effect of depression of both blood pressure and morbidity rate of
      hypertension in a population.

PMID- 1395961
TI  - [Preliminary study of aluminum content of foods and aluminum intake of residents
      in Tianjin].
AB  - Aluminum content of 64 kinds of foods in Tianjin was determined. The results
      showed that the aluminum levels in different kinds of food varied greatly, and
      most foodstuffs from natural sources (including contamination from food
      processing) contained less than 10 mg/kg. Aluminum content was higher in
      foodstuffs of plant origin, especially dry beans contained larger amounts of
      aluminum naturally. It was estimated that most Tianjin inhabitants would consume
      3-10 mg aluminum daily from natural sources, there being no significant
      difference between urban and rural inhabitants.

PMID- 1395962
TI  - [Stereotactic intracavitary irradiation of huge cystic craniopharyngiomas].
AB  - From Jan. 1988 to June 1990, 32 patients with huge cystic craniopharyngiomas were
      treated by CT-guided stereotactic injection of phosphorus-32. Among them, 14 were
      male and 18 female. Their ranged 3 to 56 years (average 20 years). The history of
      illness varied from 1 to 8 years (average 2.8 years). All patients were confirmed
      pathologically, eleven of them had recurrent tumor after craniotomy. The volume
      of cystic tumor varied from 14 to 126ml (average 32ml). 1.2-5.6mCi (average
      2.3mCi) of 32P were injected in each time. 65 injections were successfully
      performed. There were neither deaths nor serious complications. Follow-up time
      ranged from 12 to 24 months. The clinical symptoms of these patients were
      improved in 27 patients and volumes of the tumors were reduced on CT scans. The
      effective rate was 84.4%. We conclude that this technique is simple, efficient
      and safe for the treatment of huge cystic craniopharyngiomas.

PMID- 1395963
TI  - [Primary observation of prolonged survival of cultured epidermal allografts].
AB  - It is still controversial that cultured epidermal allografts can survive long. In
      this study, seventy-nine pieces of cultured epidermal sheets were grafted on the
      wounds after taking for autografts. The wounds grafted with allogeneic cultured
      epidermis healed with mean time of 7.2 +/- 1.4 days, while the wounds uncovered
      with cultured epidermis healed with the mean time of 12.8 +/- 2.5 days (P less
      than 0.005). No evident signs of allogeneic rejection were found either by
      clinical or histological observation from 20 days to one year's follow-up. In
      order to prove the existence of cultured epidermal allografts on grafted area,
      two methods were established: 1) indirect enzyme conjugated SPA assay to detect A
      or B blood group antigens with McAb; 2) polymerase chain reaction (PCR) to
      amplify Y chromosome specific DNA sequence after the female were grafted with
      cultured male epidermis. In four patients grafted with ABO blood group mismatched
      cultured epidermis, the donor antigens were found in the grafted area as long as
      35 post graft day (PGD). The recipient antigens appeared on 19 PGD. Y chromosome
      specific DNA was detected in five samples taken from two female patients grafted
      with cultured male epidermis. Of these five samples, the biopsy time was on 11,
      19, 30, 35, 92 PGD respectively. Combining the clinical and histological
      observation with the results of two methods, it can be concluded that the
      survival time of cultured epidermal allografts were definitely prolonged.

PMID- 1395964
TI  - [Percalcar Steinmann's pins fixation of intratrochaner fixation fracture.
      Clinical observation].
AB  - 80 cases of intratrochaner fractures were treated by fixation of 4 Steinmann's
      pins which were 3.5 mm in diameter and inserted percutaneously through the calcar
      and compression trabeculae and distension trabeculae respectively. They were
      compared with the cases treated by skeletal traction or fixed by Nail-plate or
      angle plate. The rate of bony union in fixed position in the percalcar
      Steinmann's pins group was 83.7%. Normal neck-shaft angle accounted to 53.1% in
      the traction group. Varus deformity occurred in 16.3% cases of the Steinmann's
      pins group, and 35.9% cases of the traction group. The deformity was most
      frequently seen in cases of type IIIa and IV. No fixation failure occurred in the
      Steinmann's pins group. The Steinmann's pins passing through the outer cortex,
      calcar and compression trabeculae produced strong fixation and it's direction was
      in parallel to the weight-bearing line of the hip, with less shearing force and
      much compression force distributed on the fracture line. The operation was done
      under local anesthesia. No blood transfusion and early mobilization were the
      advantages of this method.

PMID- 1395965
TI  - [Arterioembolization with shape memory angioembolus. Experimental study and
      clinical application].
AB  - The results of experimental study and clinical application of arterio
      embolization induced by the conical spiral or rugby spiral type of shape memory
      angioembolus(Nitinol-Conical Rugby Embolus, NT-CRE) were reported. The NT-CRE has
      a spring coil as its base line and is formed like a conical spiral or rugby
      spiral which has a two-way memory effect. Through a period of 1-48 weeks
      observation on 74 angiographic and histological specimens of 39 target arteries
      from 20 experimental dogs showed that the NT-CRE has good histocompatibility and
      is effective for embolization in large-bored arteries. Clinical application on
      target arteries of 7 patients showed successful occlusion of blood flow in 5-18
      minutes in arteries with internal diameters of 3.33-5.83 mm. The NT-CRE being of
      the two-way memory effect and its configuration of relatively close state render
      its catheterization and release into target vessel simple, save, rapid and
      effective. In the researches we have not found any complication of hemorrhage
      from ruptured blood vessels and misembolization from regurgitation.

PMID- 1395966
TI  - [E coli-induced idiopathic portal hypertension in rabbits. An experimental
      study].
AB  - An experimental model of portal hypertension was induced in healthy rabbits by
      intraportal injection of E coli or a mixture of E coli and rabbit anti-E coli
      sera. In all established models, there were significant elevation of portal vein
      pressure, increase of spleen weight, decrease of whole blood cells count,
      infiltration of inflammatory cells and fibrosis in intrahepatic portal area,
      decrease of the number and discontinuation of intrahepatic portal vein branch on
      portography with gross normal appearance of the liver. Hence this model was
      similar to that seen in human idiopathic portal hypertension (IPH) in many
      aspects. We believe that bacterial toxin and the abnormal immune reaction due to
      repeated stimulation of bacterial antigen may play a role in the pathogenesis of
      human IPH.

PMID- 1395967
TI  - [Current status of anterior cruciate ligament repair with artificial ligament].

PMID- 1395968
TI  - [Endoscopic sphincterotomy in the treatment of choledochol calculus].
AB  - Fifty patients with choledochal calculus were treated by endoscopic
      sphincterotomy (EST) and forty-nine of them were cured. Stones were excreted in
      forty-six patients spontaneously and in two patients by basket. Stones
      disappeared in one patient after extracorporeal shock wave therapy. The
      complications included gastrointestinal hemorrhage (2%), pancreatitis (2%) and
      cholangitis (4.1%). Twelve of them were followed by barium meal after EST. The
      barium was found in biliary tract in one patient and pneumatosis in another one
      without any clinical symptoms. The authors suggest that EST could be an important
      nonoperative therapy in the treatment of choledochal calculus.

PMID- 1395969
TI  - [Intraoperative transgallbladder duct endoscopy replaces conventional common duct
      exploration].
AB  - Twenty patients of cholelithiasis underwent intraoperative transcystic duct
      fiberendoscopy in whom choledochotomy was otherwise indicated. Among them
      choledocholithotomy was done endoscopically in three patients and auxiliary
      choledocho-cystic junction incision was obligatory for easy insertion of the
      fiberscope in six. No T-tube was needed after the procedure and the postoperative
      recovery was uneventful in all cases.

PMID- 1395970
TI  - [Correlativity of plasma endotoxin, plasma fibronectin and common bile duct
      pressure in severe acute cholangitis].
AB  - On the basis of common bile duct pressure measurement (CBDP) in 18 patients of
      severe acute cholangitis, plasma endotoxin (ET) was determined by modified
      synthetic chromogenic limulus amebocyte lysate assay and plasma fibronectin (FN)
      was detected with Laurell's rocket immunoelectrophoresis. CBDP was 2.23 +/- 0.49
      KPa in patient group. There was striking positive correlation between ET and
      CBDP. Preoperative ET was 202.73 +/- 88.57 ng/L in patient group which was much
      higher than 15.47 +/- 7.38 ng/L in the control (P less than 0.001). Preoperative
      FN was 141.77 +/- 82.37 mg/L in the patient group which was lower than 317.21 +/-
      12.57 mg/L in the control (p less than 0.001). Statistical differences could be
      noticed in postoperative ET and FN between the survivor and the dead. The study
      suggested that plasma ET levels are greatly influenced by pressure gradient of
      bile duct, dynamic observations of ET and FN levels are helpful to monitor
      disease course and predict prognosis.

PMID- 1395971
TI  - [Biliogenic liver abscess caused by acute obstructive suppurative cholangitis].
AB  - Biliogenic liver abscess was found by autopsy in 52 of 61 (85.2%) cases died of
      acute obstructive suppurative cholangitis (AOSC) at our hospital from 1957 to
      1980. Of the 52 cases with liver abscess, 44 (84.6%) had multiple abscesses and
      47 (90.4%) suffered complications of the rupture of liver abscess. Liver abscess
      was clinically diagnosed in only 7 of 52 cases who underwent emergency operation,
      with the predeath definite diagnosis of 13.5% (7/52). The authors considered
      biliogenic liver abscess an inevitable outcome not an accidental complication of
      AOSC when the high pressure in bile duct could not be relieved, and emphasized
      the importance of prevention, early diagnosis and treatment of liver abscess in
      order to decrease the mortality of AOSC.

PMID- 1395972
TI  - [The role of free fatty acids in the formation of cholelith].
AB  - Free fatty acids of bile were determined by gas chromatography in 57 patients
      with and without cholelithiasis. The results showed that 1. The percentage of
      free palmitic acid in total lipid was significantly higher in gallbladder stone
      group (0.38%) and duct stone group (0.32%) than that in control group (0.07%), P
      less than 0.05. 2. The percentage of free stearic acid and arachidonic acid was
      significantly higher in gallbladder stone group (0.08%, 0.09%) than that in
      control group (0.01%, 0.02%), P less than 0.05. Authors believed that the changes
      were related to the formation of fatty acid calcium in the stones and the
      oversecretion of prostaglandin in gallbladder.

PMID- 1395973
TI  - [Primary gastrointestinal malignant lymphoma. An analysis of 63 cases].
AB  - Sixty-three patients with primary gastrointestinal malignant lymphoma confirmed
      by pathology and treated in our hospital from 1973 to 1989 were reported. There
      were 30 males and 33 females, four suffering hodgkin's diseases and 59 non
      hodgkin's lymphoma, with 17 at stage I, 17 at stage II, 9 at stage III, and 20 at
      stage IV. Patients were treated by surgery, radiotherapy and chemotherapy
      separately or combined. Forty-seven patients underwent tumor extirpation. Five
      year's postoperative survival at stage I, II, and III were 84.6%, 33.3%, and
      14.2%, respectively. Surgery combined with postoperative radiotherapy and/or
      chemotherapy gave better results. The incidence, diagnosis, clinical staging and
      the therapeutic indications were discussed with a review of literature.

PMID- 1395974
TI  - Experimental transmission of Cowdria ruminantium (Rickettsiales) by the American
      reptile tick Amblyomma dissimile Koch, 1844.
AB  - A Senegalese isolate of the rickettsia Cowdria ruminantium was transmitted
      transstadially by nymphs of the American reptile tick Amblyomma dissimile. Only
      eight nymphs, fed as larvae on a Saanen goat reacting to heartwater, were
      required to transmit fatal heartwater to another susceptible goat. Since A.
      dissimile usually feeds on snakes, iguanas and lizards in central America, the
      tick is not considered to play a significant role in the transmission of
      heartwater between ruminants. However, the tick could play a role in maintaining
      a rickettsial reservoir in reptile populations, since it has been shown that an
      African reptile can be a subclinical carrier of C. ruminantium, infective to
      vector ticks.

PMID- 1395975
TI  - Control of hemorrhage from a mucous fistula with Foley catheter tamponade.
AB  - Massive hemorrhage from the colon is always a problem. When that bleeding occurs
      in a defunctionalized colonic mucous fistula, the surgeon can approach the
      bleeding site from both ends simultaneously. Two methods of controlling
      hemorrhage from a mucous fistula with the assistance of Foley catheter tamponade
      are presented.

PMID- 1395976
TI  - Steroid complications in patients with ulcerative colitis.
AB  - Physicians treating patients with ulcerative colitis are confronted with the
      difficult task of deciding whether medical or surgical treatment is best for
      their patients. There are no definitive criteria to indicate when medical therapy
      should be exchanged for definitive surgery. Even in patients who respond well to
      glucocorticoid treatment, the side effects of these drugs may necessitate
      surgery. We reviewed the steroid complications of our operative cases
      retrospectively. Although ulcerative colitis was usually in remission, severe
      steroid complications were no longer tolerable and definitive surgery was
      required. We also reviewed the literature regarding the adverse effects of
      steroid. Because of advances in sphincter-preserving surgery, re-evaluation of
      the treatment of ulcerative colitis is necessary. Although conservative treatment
      remains the first choice, tolerance of irreversible side effects (especially in
      children) no longer seems to be justified. In such patients, early definitive
      surgery may offer more than it appears to sacrifice.

PMID- 1395977
TI  - Short-chain fatty acid enemas: a cost-effective alternative in the treatment of
      nonspecific proctosigmoiditis.
AB  - The purpose of this study was to perform a randomized, prospective comparison of
      corticosteroid enemas (CS--100 mg of hydrocortisone/60 cc P.R. q.h.s.; n = 12),
      mesalamine enemas (5-ASA--4 g/60 cc P.R. q.h.s.; n = 19), and short-chain fatty
      acid enemas (SCFA--60 cc P.R. b.i.d.; n = 14) for the treatment of
      proctosigmoiditis. Patients presenting to the Ferguson Clinic with the diagnosis
      of idiopathic proctosigmoiditis were evaluated for age, sex, prior history of
      proctitis, duration of symptoms prior to presentation, endoscopic scoring, and
      mucosal biopsies. Clinical evaluation was performed at two-week intervals for six
      weeks, with repeat biopsies taken at six weeks. There was no significant
      difference with respect to age, male/female ratio, past history of
      proctosigmoiditis, length of colorectum involved at the time of initial
      presentation, symptom resolution, and endoscopic and histologic improvement among
      the three treatment groups. Recovery occurred in a similar proportion in each of
      the three groups: CS, 10/12; 5-ASA, 17/19; and SCFA, 12/14. The cost of six weeks
      of treatment was: CS, $71.82; 5-ASA, $347.28; and SCFA, $31.50. This study
      indicates that SCFA enemas are equally efficacious to CS or 5-ASA enemas for the
      treatment of proctosigmoiditis at a significant cost savings.

PMID- 1395978
TI  - Clinical classification of perianal Crohn's disease.
AB  - Assessment of the efficacy of therapeutic approaches to anal lesions of Crohn's
      disease is frustrated by the lack of precise definition of its various
      manifestations. A classification that is clinical and based on anatomic and
      pathologic aspects is presented; it has been derived from a 20-year prospective
      study of anal Crohn's disease in Cardiff. Conceptually, the classification is
      analogous to the TNM system for cancer. The main classification (U.F.S.) defines
      the presence of Ulceration, Fistula/abscess, and Stricture, qualified by numeric
      values reflecting severity (0 = not present, 1 = limited clinical impact, and 2 =
      severe). A subsidiary classification (A.P.D.) defines Associated conditions,
      Proximal intestinal involvement, and Disease activity. In addition, the
      classification may be used in a detailed form for research or comparative
      purposes or in a simple form defining only the dominant lesions for routine
      clinical use. General use of the classification would make it possible to compare
      in detail incidence, management, and results of treatment in different centers.

PMID- 1395979
TI  - The fate of patients following polypectomy alone for polyps containing invasive
      carcinoma.
AB  - Eighty-two patients with colon and rectal polyps containing invasive
      adenocarcinoma treated by polypectomy alone were studied. Seven of 34 patients
      (21 percent) with sessile lesions had an adverse outcome, including five local
      recurrences and two distant metastases. They occurred from 4 to 68 months after
      the polypectomy. Forty-seven pedunculated polyps with invasion to the head (Level
      1) or to the stalk (Level 3) and one polyp to the base of the stalk (Level 4) had
      no evidence of local recurrence or signs of metastasis. Twenty-eight percent of
      patients were found to have adenomatous polyps, and 4 percent had malignant
      polyps during the follow-up examinations (range, 3-119 months; mean, 53 months).
      The findings suggested that pedunculated polyps with invasion to the head (Level
      1), neck (Level 2), or stalk (Level 3) can be safely treated with a complete
      polypectomy provided that the carcinoma is not undifferentiated. Sessile lesions
      as well as Level 4 pedunculated lesions should be treated aggressively. If
      resection is not performed, a long-term follow-up in these patients is essential.

PMID- 1395980
TI  - Anastomotic-vaginal fistula after colorectal surgery.
AB  - The most feared complication of anterior and low anterior resection is
      anastomotic dehiscence. Although most leakages remain clinically silent, some may
      lead to formation of a colovaginal fistula. At the Lahey Clinic Medical Center,
      the records of nine patients with colovaginal fistula as a complication of
      colorectal surgery were reviewed to determine clinical characteristics and
      optimal management. The mean age was 63.7 years (range, 47-72 years). The initial
      indications for surgery were carcinoma of the rectum (n = 4), diverticular
      disease (n = 3), and closure of the colostomy after Hartmann's procedure (n = 2).
      Hysterectomy had been performed earlier in seven patients (78 percent). The end
      to-end anastomosis (EEA) stapling device was used in five patients, and four
      patients had a handsewn anastomosis. The fistula developed within 23 days after
      surgery and usually originated within 8 cm of the anal verge. Two patients
      underwent immediate diverting transverse colostomy. None of the seven patients
      who were initially managed medically had spontaneous closure of the fistula. High
      fistulas were successfully treated by colorectal resection in two patients,
      whereas low fistulas healed after transanal repair without colostomy in two
      patients. These results suggest that previous hysterectomy predisposes to
      development of a colovaginal fistula after colorectal surgery. Not all patients
      require fecal diversion. Colorectal resection for high fistulas and transanal
      repair for low fistulas appear to be viable options for treatment.

PMID- 1395981
TI  - Anal endosonography: relationship with anal manometry and neurophysiologic tests.
AB  - Thirty-seven patients were referred for evaluation of anal function; their
      clinical diagnoses were traumatic fecal incontinence (13), idiopathic (pudendal
      neuropathy) fecal incontinence (7), fecal soiling (9), and other (8). In all
      patients, anal endosonography (sphincter defects and internal sphincter thickness
      [IST]) and anal manometry (maximal basal pressure [MBP] and maximal squeeze
      pressure [MSP]) were performed. In 18 patients, neurophysiologic tests (EMG
      maximal contraction pattern [MCP], single-fiber EMG [fiber density; FD], and
      pudendal nerve terminal motor latency [PNTML]) were also performed.
      Endosonography demonstrated in seven patients both an internal and external
      sphincter defect (Group 1), in seven patients an internal sphincter defect and in
      one patient an external sphincter defect (Group 2), and in 22 patients no
      sphincter defect (Group 3). There was a significant difference among these three
      groups for MBP and MCP, the lowest being in Group 1. Between the patients with
      traumatic fecal incontinence and idiopathic fecal incontinence, no differences in
      IST, MBP, MSP, MCP, FD, and PNTML were found. In two patients with a suspected
      obstetric trauma, there was an unexpected additional severe pudendal neuropathy.
      In one patient with a suspected obstetric trauma, no damage of the anal
      sphincters could be demonstrated. In one patient with suspected idiopathic fecal
      incontinence, there was an additional, unsuspected defect of the internal
      sphincter. There was concordance between endosonography and EMG in the mapping of
      the external sphincter. Clinical diagnoses can be misleading in differentiating
      between traumatic and idiopathic fecal incontinence; anal endosonography provides
      unsuspected and additional information about the sphincters; PNTML can reveal
      unsuspected neuropathy in traumatic fecal incontinence. Therefore, the
      combination of endosonography and PNTML is promising in selecting patients for
      surgery.

PMID- 1395982
TI  - Dysplasia in chronic ulcerative colitis: implications for colonoscopic
      surveillance.
AB  - Mucosal dysplasia has been used as a marker for patients with chronic ulcerative
      colitis considered to be most at risk of developing cancer, and its
      identification is the basis for colonoscopic surveillance programs. To evaluate
      the reliability of this premise, colectomy specimens from two groups of patients
      who had undergone surgery for chronic ulcerative colitis (50 with cancer and 50
      without) were retrieved. The groups were matched by age, sex, duration of
      disease, disease extent, and symptoms at the time of surgery. Using a standard
      technique of multiple random biopsies, we utilized the standard colonoscopic
      biopsy forceps to obtain four biopsies from mucosa that was not macroscopically
      suspicious for dysplasia or cancer in eight defined regions in each of the 100
      colon specimens. This technique mimicked exactly the methods used in our clinical
      surveillance program. All 3,200 biopsies were evaluated blindly by one
      pathologist for presence and grade of dysplasia. Twenty-six percent of colons
      with an established cancer harbored no dysplasia in any biopsy from any region in
      the colon. While an overall association between the presence of cancer and high
      grade dysplasia was detected (relative risk = 9.00; 95 percent CI of 2.73-29.67),
      the sensitivity and specificity of random colonic biopsies to detect concomitant
      carcinoma were 0.74 and 0.74, respectively. These findings prompt concern that
      reliance on random biopsies, obtained during colonoscopic surveillance, may be
      misplaced.

PMID- 1395983
TI  - Colorectal trauma: primary repair or anastomosis with intracolonic bypass vs.
      ostomy.
AB  - This prospective, randomized, controlled study was undertaken to compare primary
      repair or anastomosis with intracolonic bypass vs. ostomy in severe colon and
      intraperitoneal rectal injury. Patients were randomized at surgery following
      confirmation of injury. Data collected included demographics, mechanism and
      location of injury, trauma score (TS), injury severity score (ISS), penetrating
      abdominal trauma index (PATI), complications, length of hospital stay, and
      hospital charges. Twenty-two patients were studied: 11 with intracolonic bypass
      and 11 controls. The experimental and control groups were statistically similar
      in demographics and mechanism of injury, severity of injury (TS = 13.8 vs. 12.8;
      ISS = 27.5 vs. 24.2; PATI = 40.5 vs. 35.0), and complication rate. Length of stay
      (12.2 days vs. 20.7 days) and charges $27,885 vs. $53,599) tended to be greater
      in controls, and the comparison did not include subsequent colostomy closure.
      This study supports intracolonic bypass as a safe alternative to ostomy in severe
      colon and intraperitoneal rectal trauma.

PMID- 1395984
TI  - Intraperitoneal hyperthermic treatment for peritoneal dissemination of colorectal
      cancers.
AB  - Continuous hyperthermic peritoneal perfusion (CHPP) combined with administration
      of anticancer drugs was performed in eight colorectal cancer patients with
      peritoneal dissemination. An overall response rate of 50 percent was achieved in
      the eight patients. Two of three complete responders are long, recurrence-free
      survivors for 15 and 30 months. The two-year survival has been achieved in 18.8
      percent of the patients receiving CHPP, and this rate is significantly higher
      than the rates in P2 and P3 patients who did not receive CHPP. The complications
      of CHPP with administration of anticancer drugs were mild bone marrow suppression
      in two (25 percent) of the eight patients and also a mild grade of renal
      dysfunction in one (12.5 percent), though not lethal. The results suggest that
      the combination of CHPP with the administration of anticancer drugs is a safe and
      effective therapy for peritoneal dissemination of colorectal cancers.

PMID- 1395985
TI  - Colostomy plug devices: a possible new approach to the problem of incontinence.
AB  - The authors report their experience in the use of the Conseal (Coloplast S.p.A.,
      Bologna, Italy) Colostomy Plug, a new device for the regulation of continence in
      patients with colostomies. The devices were tested on 57 patients divided into
      two groups: Group A (36 patients) fit with a two-piece Conseal system and Group B
      (21 patients) fit with a one-piece Conseal system. All patients had the same
      colostomy type, and all were trained for self-irrigation. The objectives of this
      randomized, prospective study were to determine compliance with the different
      systems, to identify the advantages, and to verify the possible different
      applications among the population of irrigated patients. The following results
      were obtained. Regarding compliance: Group A's results were excellent in 22.2
      percent and good in 52.7 percent of patients. Group B had better compliance than
      Group A (excellent in 66.6 percent and good in 19 percent of patients). Regarding
      controlled evacuation, continence time, and silent gas emission: in Group A, the
      device permitted controlled evacuations (23.8 percent of patients practicing
      daily washouts) with silent and odorless gas emission (100 percent of cases). In
      Group B, the results concerning improvement in continence were good (33.3 percent
      of patients) and excellent concerning the emission of flatus. Regarding the
      potential use of both systems in different groups of self-irrigated patients: the
      study has revealed the Conseal Uni-system as being ideal for patients with a well
      constructed stoma, slight gas distention, and a better psychologic adaptability
      to larger-sized systems. In all other cases, the alternative two-piece system is
      more suitable, owing to the better safety it offers.

PMID- 1395987
TI  - Accuracy of colonoscopy for the detection of colorectal polyps.
AB  - The findings at colonoscopy were compared with the pathologic findings of the
      surgical specimen in 235 patients who underwent a colon resection for a primary
      colorectal neoplasm from January 1980 to December 1987 at Roswell Park Cancer
      Institute. Seven patients (3 percent) were found to have synchronous primary
      colon carcinomas, and 100 patients (43 percent) were found to have synchronous
      adenomatous polyps identified by colonoscopy and/or pathology. In patients with
      polyps 10 mm or greater in diameter, the findings on colonoscopy agreed with the
      pathology report 96 percent of the time. When polyps of all sizes were included,
      with many less than 5 mm in diameter, colonoscopy agreed with the pathology in 89
      percent of patients. When only the area of the colon resected was used to
      determine the ability of colonoscopy to locate polyps, 58 percent of polyps of
      all sizes were located. The majority of the missed polyps were adjacent to a
      carcinoma. One cecal carcinoma was not seen by colonoscopy because of technical
      inabilities to reach the cecum. A second carcinoma (20 mm x 17 mm) was not seen
      at the splenic flexure.

PMID- 1395986
TI  - Low Hartmann's procedure for severe anorectal Crohn's disease.
AB  - Perineal wounds often fail to heal following proctectomy for Crohn's disease.
      Twenty-five patients with severe anorectal Crohn's disease and perineal fistulas,
      necessitating excisional surgery, underwent a low Hartmann's procedure in lieu of
      a standard proctectomy. Fifteen of the 25 (60 percent) patients had a completely
      healed perineum and required no further surgical therapy. Although perineal
      disease persisted in the other 10 patients, their perinea were much improved
      compared with the initial presentation. Following a low Hartmann's procedure, the
      rectal stump becomes atrophic and anoperineal disease regresses, thereby
      permitting subsequent perineal proctectomy in less inflamed tissues. Since only a
      3-cm to 5-cm cuff of rectum was retained from the initial surgery, a perineal
      intersphincteric approach could be employed and no abdominal dissection was
      necessary. Of the 10 patients who subsequently underwent perineal proctectomies,
      three patients still have an unhealed perineum. Twenty-two of the 25 (88 percent)
      patients have a completely healed perineum (mean follow-up period, 69.1 months).
      No attempt was made to establish intestinal continuity in any of the 25 patients.
      We conclude that the problem of the unhealed perineal wound can be averted with
      this approach, thereby reducing the long-term morbidity to the patient.

PMID- 1395988
TI  - Colon trauma--clinical staging for surgical decision making. Analysis of 119
      cases.
AB  - A retrospective study is presented of 119 patients admitted to the Central
      Hospital of the Venezuelan Institute of Social Security, in Caracas, between 1982
      and 1990, with the diagnosis of colon trauma. Several parameters including age,
      etiology, time elapsed between the accident or assault and hospital admission,
      preoperative and postoperative hemoglobin and diastolic blood pressure,
      associated lesions, procedure practiced, complication rate, and hospital
      mortality are reviewed. The second and third decades of life appear most often
      involved. Most patients reached the hospital within the first four hours of the
      accident or assault. Anemia, sustained diastolic hypotension, and number of
      organs involved in addition to the colon were important prognostic factors for
      complications. Apparently the surgical procedure, with simple suture or
      resection, mostly without "protective" colostomy, was not very relevant. Hospital
      mortality was 2.4 percent. A staging system based on clinical conditions for
      decision making in the operating room was used in an attempt to inject some
      objectivity into the surgical approach.

PMID- 1395989
TI  - Role of wrapping in concomitant intra-abdominal aneurysm and colorectal
      carcinoma. Report of three cases.
AB  - The therapeutic measure against concomitant intraabdominal aneurysm and
      colorectal carcinoma is still a dilemma. Here we report the clinical courses of
      three cases of colorectal carcinoma coincidental with moderate-sized abdominal
      aortic or iliac artery aneurysm in those who underwent operations during a recent
      three-year period. Resection of malignant lesion and wrapping of aneurysm were
      carried out in all three patients simultaneously. Carcinoma was staged by Dukes
      classification as A in one patient and B in two patients. All tolerated surgery
      well without any signs of complications. Two-year or three-year follow-up shows
      that they have continued to do well, with no further symptoms of abdominal aortic
      aneurysm, peripheral vascular disease, or recurrence of colorectal carcinoma. We
      conclude that, if the aneurysm is not about to rupture and the carcinoma is in an
      advanced stage, then the carcinoma should be resected, associated with interim
      aneurysmal wrapping. However, both lesions need to be resected eventually for
      long-term survival.

PMID- 1395990
TI  - Technical modification to laparoscopic appendectomy.
AB  - An alternative technique for laparoscopic appendectomy is described. The isolated
      appendix is exteriorized through the trocar wound, ligated, and resected. The
      cecum is then returned to the abdomen.

PMID- 1395991
TI  - Chronic administration of cyclosporin A induces a decrease in hepatic excretory
      function in man.
AB  - Chronic administration of cyclosporin A may induce cholestasis in a few patients.
      The purpose of this study was to examine the effect of chronic administration of
      cyclosporin A on serum bile acid levels, serum bilirubin concentration, and
      bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted
      patients with normal serum alanine aminotransferase activity receiving
      cyclosporine A during a mean duration of 33 months (range 7-54) were compared to
      20 matched kidney-transplanted patients with normal serum alanine
      aminotransferase receiving azathioprine for a mean duration of 34 months (range 6
      72). As compared to azathioprine-treated patients, patients treated with
      cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an
      increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in
      bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These
      results suggest that cyclosporin A induces a decrease in hepatic excretory
      function in man.

PMID- 1395992
TI  - Effects of interferon-alpha therapy on serum and liver HBV DNA in patients with
      chronic hepatitis B.
AB  - The aim of this study was to evaluate the effect of interferon-alpha therapy on
      serum and liver HBV DNA in 20 patients with chronic hepatitis B and to correlate
      the presence or absence of HBV DNA with the clinical response. There were 11
      responders and all lost HBV DNA from the serum. Ten of the 11 were followed for
      36 months following IFN treatment and remained well with absence of HBeAg and HBV
      DNA from the serum and with normal ALT. Five also lost HBsAg. HBV DNA became
      undetectable in the liver of nine of 10 of these patients in whom liver tissue
      was available for study. HBV DNA persisted in the liver of seven of nine
      nonresponders and was not detected in two in spite of the presence of HBV DNA and
      HBeAg in the serum of these two patients. We conclude that IFN may induce long
      remissions in patients with chronic hepatitis B with loss of HBV DNA from the
      serum and that occasionally HBV DNA may persist in the liver of such patients.

PMID- 1395993
TI  - Profile of alkaline phosphatase isoenzymes in ten patients poisoned by mushrooms
      of the genus Lepiota.
AB  - Mushrooms of the genus Lepiota (helveola and bruneo-incarnata), similar to those
      of the genus Amanita, contain amatoxins. Amatoxins, especially amanitin, cause
      cellular destruction by inhibiting RNA polymerase. Due to the hepatic toxicity of
      these mushrooms, we have assessed their incidence on alkaline phosphatase levels
      and on its isoenzymes. Total alkaline phosphatase activity levels were not found
      to be increased except in two patients, and then only moderately. As regards
      isoenzymes, the occurrence of a double hepatic fraction in five of the 10
      patients, is the most remarkable finding. There seems to exist a relatively close
      correspondence between the occurrence of a hepatic2 fraction correlating with
      those of urine amanitin. We conclude that the hepatic2 fraction proves to be
      important in assessing liver damage by mushroom poisoning because of its
      correlation with the patient's degree of poisoning.

PMID- 1395994
TI  - Analysis of clinical course and prognosis of culture-positive spontaneous
      bacterial peritonitis and neutrocytic ascites. Evidence of the same disease.
AB  - The clinical significance and prognosis of culture-negative neutrocytic ascites
      in cirrhotic patients is a controversial topic. In the present study, the
      clinical and humoral presentation and the short- and long-term prognosis were
      analyzed in 36 patients with cirrhosis and culture-positive spontaneous bacterial
      peritonitis and in 28 patients with cirrhosis and ascitic fluid polymorphonuclear
      count greater than 250/mm3, a negative ascitic fluid culture, and without
      previous antibiotic therapy. On admission there were no significant differences
      between groups related to age, sex, alcoholism, fever, abdominal pain, serum
      albumin, serum urea, serum creatinine, Child-Pugh score, polymorphonuclear count,
      and total protein concentration in ascitic fluid. A greater frequency of positive
      blood culture was found in patients with spontaneous bacterial peritonitis (15/21
      vs 2/18) (P < 0.001). Mortality during the first episode was 36% in patients with
      spontaneous bacterial peritonitis and 46% in patients with culture-negative
      neutrocytic ascites (NS). Mortality during follow-up was high and survival
      probability at 12 months was 32% in spontaneous bacterial peritonitis and 31% in
      culture-negative neutrocytic ascites. The probability of recurrence at 12 months
      was 33% in spontaneous bacterial peritonitis and 34% in culture-negative
      neutrocytic ascites. Our results show that spontaneous bacterial peritonitis and
      culture-negative neutrocytic ascites are variants of the same disease with a high
      mortality and poor prognosis.

PMID- 1395995
TI  - Disturbance of plasma thyroid hormone levels after experimental liver
      transplantation. Is there an association with primary graft nonfunction?
AB  - It has been suggested recently that preoperative plasma thyroid hormone levels
      may be used to predict the success of liver transplantation in prospective
      recipients and also perhaps that postoperative levels may be used to identify
      rejection. In the present study of unimmunosuppressed porcine recipients of liver
      allografts, two groups of animals were identified--those that died within five
      days postoperatively and the other group that were longer survivors. On the first
      postoperative day plasma levels of total and free T4 and total and free T3
      declined and of total rT3 increased. In survivors these levels returned towards
      normal within three days, while they persisted in nonsurvivors. As there was no
      obvious cause of graft failure in nonsurvivors, the state might be considered to
      represent primary graft nonfunction in pigs, and the changes in plasma thyroid
      hormone levels may be predictive of this condition; a study in patients may
      confirm this.

PMID- 1395996
TI  - Hepatic cavitation. A marker of transient hepatocellular injury during biliary
      lithotripsy.
AB  - Sonographically visible microbubbles attributable to cavitation effects have been
      observed in bile (within the gallbladder), in hepatic vessels, and within the
      liver of patients undergoing biliary lithotripsy. Cavitation effects are believed
      to contribute to stone fragmentation and possibly tissue injury during
      lithotripsy. To study the latter, the relationship between intraparenchymal
      hepatic cavitation and serum transaminase activity and clinical follow-up was
      analyzed in 81 patients undergoing 164 lithotripsy treatments. Seventy-one
      treatments (43%) resulted in sonographically evident microbubbles in the liver
      parenchyma during lithotripsy. A temporary, yet statistically significant (P <
      0.01) rise in SGOT and SGPT was observed within 2 hr of completion of lithotripsy
      compared to those patients without hepatic microbubbles. All but one patient had
      a return to pretreatment baseline levels of SGOT and SGPT by two weeks after
      lithotripsy. In this patient, persistent elevation of transaminases was
      attributed to the delayed passage of fragments and not to any sequelae from
      hepatic cavitation effects. Ultrasound immediately after, two weeks after, and 3
      12 months after lithotripsy showed no hepatic structural abnormalities. Ursodiol
      administration at the time of treatment did not predispose to hepatic cavitation
      or elevation of transaminase. Detection of hepatic microbubbles during
      lithotripsy is a marker of hepatocellular injury. Their correlation with
      transaminase elevation refutes the contention that transaminasemia results solely
      from fragment passage after lithotripsy. Although not associated with
      recognizable structural damage or long-term sequelae, cavitation effects and
      transaminasemia reiterate that shockwaves are not entirely benign as they
      traverse parenchymal organs.

PMID- 1395997
TI  - Patients with uncomplicated cholelithiasis acidify bile normally.
AB  - Reports have suggested that patients with gallstones have gallbladder bile that
      is less acidic and more saturated with calcium carbonate than patients without
      gallstones. This failure to acidify bile may play a role in the formation of
      gallstones. We, therefore, compared gallbladder bile pH, ionized calcium, and
      calcium carbonate saturation index from patients undergoing either incidental
      gallbladder removal (controls, n = 23) or elective cholecystectomy for gallstones
      (n = 55). Gallstones were classified as either cholesterol (n = 39) or black
      pigment (n = 16) stones. No difference in gallbladder bile pH was noted among the
      controls, cholesterol stone, and pigment stone patients. In addition, no
      difference in ionized calcium concentration or CCSI was noted among the three
      groups. The pH in additional patients (n = 49) with acute cholecystitis, common
      bile duct obstruction, biliary tract infection, and cystic duct obstruction was
      significantly more acidic. We conclude that neither a defect in bile
      acidification nor increased saturation of calcium carbonate explains why human
      cholesterol or pigment gallstones form.

PMID- 1395998
TI  - Secretion of biliary calcium is increased in dogs with pigment gallstones.
AB  - We have previously demonstrated that gallbladder bile is supersaturated with
      calcium bilirubinate in a canine dietary model of pigment gallstones.
      Supersaturation resulted from combined increases in the concentrations of both
      biliary calcium and unconjugated bilirubin. The elevations in biliary calcium and
      unconjugated bilirubin concentrations remain unexplained but could possibly be
      due to increases in hepatic or ductular secretion, alterations in bile
      composition with respect to calcium-or bilirubin-binding affinity, decreases in
      absorption from the gallbladder lumen, or, in the case of unconjugated bilirubin,
      production within the lumen by hydrolysis of conjugated bilirubin. Here, we study
      a single possible cause for the observed increase in biliary calcium
      concentration during pigment gallstone formation in dogs. Secretion of calcium
      into bile in dogs with pigment gallstones before and after infusion of the bile
      salt, taurocholate, was compared to normal dogs. A significant increase in bile
      acid-independent bile flow and calcium output (CaO) was observed at any given
      bile acid output. Thus, plots of bile flow and CaO versus bile acid output
      yielded two separate functions in normal dogs and dogs with pigment gallstones.
      The slopes of these functions were similar, but intercepts extrapolated to zero
      bile acid output were markedly different, indicating that bile acid-independent,
      but not bile acid-dependent, bile flow and CaO was increased. The increase in CaO
      was not due to secretion of bile with increased concentrations of calcium but
      rather to the increases in the rate of bile flow. These findings might, in part,
      explain elevated calcium concentrations since increased amounts of calcium would
      be presented to the gallbladder in these animals during gallstone formation.

PMID- 1395999
TI  - Biliary pressure variation in coordination with migrating motor complex of
      duodenum in patients with cholecystectomy and effects of morphine and cerulein.
AB  - Pressures in the common bile duct and duodenum were continuously measured with
      two pressure microtransducers placed by endoscopy in 10 postcholecystectomy
      patients. A complete cycle of the migrating motor complex of the duodenum was
      obtained in seven patients, its length ranging from 62 to 174 min with a mean of
      114 min. The biliary pressure showed a transient elevation of 5.0 +/- 0.6 (mean
      +/- SEM) mm Hg (P < 0.001) in concert with phase III of the duodenal cycle in all
      10 patients, whereas it remained stable during other phases. Intramuscular
      morphine (0.2 mg/kg) given to induce spasm of the sphincter of Oddi 20 min after
      the passage of phase III invariably produced an activity front in the duodenum
      and a sustained increase in the biliary pressure, the magnitude of which was 8.3
      +/- 0.9 mm Hg. The biliary pressure raised by morphine dropped after an
      intravenous injection of cerulein (0.1 microgram/kg) as a sphincter relaxant.
      These findings indicate that the biliary pressure rises transiently at phase III
      of the duodenal cycle in patients after cholecystectomy, probably due to
      contractions of the sphincter of Oddi.

PMID- 1396000
TI  - Measurement of segmental transit through the gut in man. A novel approach by the
      biomagnetic method.
AB  - The techniques commonly used to evaluate the transit of contents through the gut
      feature some limitations for being either inaccurate, invasive, inconvenient, or
      potentially dangerous for the subjects. Aim of this study was to establish a
      safe, noninvasive and accurate technique for the measurement of segmental oroanal
      transit time. We localized an orally ingested magnetic marker by means of a
      biomagnetic instrumentation that allows us to identify in a three-dimensional
      pattern the position of a biomagnetic source inside the body. The biomagnetic
      localizations were compared with the anatomical data obtained by magnetic
      resonance imaging investigations. The study was performed in 12 healthy subjects,
      and scans were taken every hour up to the arrival of the marker into the cecum;
      thereafter, scans were taken every 4 hr up to the elimination of the marker. In
      99% of the isofield maps obtained from each field scan, the marker was localized
      within the bowel walls. The mean oroanal transit time was 56 +/- 5 hr, the mouth
      to-cecum transit time was 13 +/- 1.7 hr, and the total colonic transit time was
      43.5 +/- 5 hr (mean +/- SEM). Segmental colon transit did not show major
      differences among the regions considered, although most of the time was spent in
      the right colon. In fact, a good correlation was found between transit time
      through the right colon and oroanal and total colonic transit (r = 0.77, P <
      0.02, r = 0.79, P < 0.02 respectively). In conclusion, this method might be a
      safe alternative to the techniques presently used in the clinical setting for the
      measurement of intestinal transit.

PMID- 1396001
TI  - Cigarette smoking and nicotine delay postprandial mouth-cecum transit time.
AB  - The acute effects of both cigarette smoking and nicotine on postprandial mouth
      cecum transit were studied in 20 habitual smokers, 10 males and 10 females. Mouth
      cecum transit time was measured by the breath hydrogen technique, following
      ingestion of a standard mixed liquid meal. Each subject was studied on four
      separate occasions, either (1) sham or actively smoking two standard cigarettes,
      commencing 20 min after the meal, or (2) chewing two placebo or nicotine tablets
      over a 60-min period, commencing immediately after the meal. The time of
      administration of these stimuli was designed to minimize the effects on mouth
      cecum transit time of alterations in gastric emptying. Mouth-cecum transit time
      was prolonged in response to both smoking [median and interquartile range: 120
      (95, 150) min vs 100 (75, 140) min, P = 0.01] and nicotine [120 (80, 170) min vs
      100 (70, 140) min, P = 0.002]. No difference was observed between sexes with
      respect to nicotine; the effect of smoking on mouth-cecum transit time, however,
      was less pronounced in females compared to males [difference active-placebo: 10
      (10, 20) min vs 35 (20, 60) min, P = 0.01]. We conclude that acute cigarette
      smoking delays mouth-cecum transit time, an effect most likely due to nicotine.

PMID- 1396002
TI  - Effects of gender, age, and body mass index on gastrointestinal transit times.
AB  - This study aimed to assess separately the effects of gender, age, and body mass
      index on gastric emptying, small intestinal transit, and colonic transit times of
      a meal containing 99mTc-labeled cellulose fiber and 2- to 3-mm 111In-labeled
      plastic particles. Seventeen healthy young subjects (nine men; eight women; age
      21-27 years; body mass index 18.4-25.1 kg/m2) and 16 healthy older subjects
      (eight men; eight women; age 55-74 years; body mass index 19.8-36.0 kg/m2) were
      studied. All transit variables were unaffected by gender. The older subjects had
      a slower mean colonic transit time of radiolabeled plastic particles than the
      young subjects (P < 0.05). Age did not affect mean gastric emptying or mean small
      intestinal transit times of the radiolabeled markers. An inverse association was
      found between body mass index and mean gastric emptying time of radiolabeled
      cellulose fiber (P < 0.02). Body mass index had no influence on other transit
      variables. The study revealed a considerable intersubject and a somewhat smaller
      intrasubject variability in mean gastric emptying, mean small intestinal, and
      mean colonic transit times.

PMID- 1396003
TI  - Differences between jejunal myoelectric activity after a meal and during phase 2
      of migrating motor complexes in healthy humans.
AB  - Using an intraluminal probe with six pairs of annular electrodes, the myoelectric
      activity of the proximal jejunum was recorded during 48-hr sessions in 16 healthy
      volunteers receiving evening and noon meals (1000 kcal) and breakfast (400 kcal).
      In 10 subjects receiving no drug, the characteristics of the migrating motor
      complexes (period, duration of each phase, velocity of propagation of phase 3,
      duration of the postprandial disruption) varied markedly between subjects but
      were relatively constant from the first to the second day of recording. Single
      spike bursts propagated at a rate of 2-5 cm/sec, clusters of 3-10 spike bursts
      propagated at a rate of 0.5-1 cm/sec, and similar clusters recurring repetitively
      each 1.5-2 min were observed after the meals and very rarely in the fasted state
      during phase 2 of nocturnal migrating motor complexes. In six subjects, oral
      administration of codeine (50 mg) 1 hr before a meal induced migrating motor
      complexes in the postprandial state, with characteristics similar to that
      observed in the fasted state except a longer duration of phase 2. Single spike
      bursts and isolated and repetitive clusters of spike bursts were observed during
      phase 2 of the codeine-induced migrating motor complexes and after meals preceded
      by placebo, but very rarely during the phase 2 of nocturnal (fasted state)
      migrating motor complexes. It is concluded that the patterns of jejunal
      contractions consisting of propagated single spike bursts and isolated or
      repetitive spike bursts characterize the postprandial state in healthy humans and
      are dependent upon digesta flow.

PMID- 1396004
TI  - Mechanisms for postprandial release of motilin in humans.
AB  - Plasma concentrations of motilin rise in the first 30 min following the ingestion
      of a meal in man. To elucidate the mechanisms of this postprandial motilin
      release, we verified the effect of cerebral stimulation and of gastric
      distension, both events normally occurring in the early postprandial period, on
      plasma motilin concentrations. Cerebral stimulation was induced by modified sham
      feeding (MSF) and gastric distension was done by inflating (with 0, 60, 240, or
      480 cc of air) a latex balloon positioned in the gastric fundus. The experiments
      were performed in healthy volunteers where antroduodenal contractile activity was
      continuously recorded and where plasma motilin was measured each 10 min. The
      stimuli were administered 30 min after a phase III of the migrating motor complex
      (MMC) was seen migrating from the antrum to the duodenum. The interval period
      between two successive spontaneous peak increases in plasma motilin was estimated
      at 113.7 +/- 8.5 min in 24 historical control subjects, and it lasted 97 +/- 13
      min in the five control volunteers here distended with 0 cc of air (P = NS). This
      interval was significantly (P < 0.05) shortened with MSF (70 +/- 6.3 min) or
      following distension with 60 cc (60 +/- 11.4 min), 240 cc (54 +/- 1.9 min) or 480
      cc of air (45 +/- 3.2 min). During the 60-min period following the administration
      of the stimuli, phase IIIs were not seen in the subjects distended with 0 cc of
      air or in those submitted to MSF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396005
TI  - Assessment by prolonged ambulatory manometry of the effect of oral cisapride on
      proximal small bowel inter-digestive motility.
AB  - The effects of cisapride, given orally at standard therapeutic dosage (10 mg
      tds), on proximal small bowel interdigestive motility in ten healthy volunteers
      was assessed by prolonged ambulatory manometry. Cisapride did not alter the
      duration of the MMC cycle, duration of phase II or the propagation rate of phase
      III in either the daytime or nighttime periods. However, when compared to
      studies, in which subjects received no drug, both nighttime and daytime phase II
      mean contractile amplitude, but not contractile incidence, were significantly
      increased (P < or = 0.001) by cisapride. Cisapride significantly increased the
      incidence of distally propagated clustered activity. We conclude that the major
      effects of cisapride on healthy small bowel motor function is to increase the
      mean contractile amplitude and incidence of distally propagated clustered
      activity.

PMID- 1396006
TI  - Significance and regulation of gastric secretion of platelet-activating factor
      (PAF-acether) in man.
AB  - Platelet-activating factor (PAF) has been implicated in the pathogenesis of acute
      inflammatory and ulcerative diseases of the upper gastrointestinal tract. In the
      present study, we compared the gastric output of PAF and its precursors with
      gastric acid output, in patients with various upper gastrointestinal tract
      diseases and healthy controls. PAF and precursors were also extracted from
      gastric biopsies from subjects with chronic gastritis and/or gastric colonization
      by Helicobacter pylori. Under basal conditions, hourly gastric PAF output
      increased in esophagitis and erosive gastritis, but not in duodenal ulcer or
      Zollinger-Ellison syndrome. In the gastric juice of duodenal ulcer patients, PAF
      output rose after secretin, but in patients with Zollinger-Ellison syndrome, PAF
      was only detected when gastric acid secretion had been reduced by antisecretory
      drugs and no concurrent changes were observed in serum gastrin levels. After
      pentagastrin, patients and controls exhibited a significant decrease in PAF
      output and a negative correlation was found between PAF and acid outputs (r = 
      0.57, p < 0.01). When PAF was incubated with gastric juice in vitro, it underwent
      degradation irrespective of the medium pH. We found no relation between the
      outputs of PAF and precursors and the severity of gastritis or gastric
      colonization by H. pylori. Overall, these results suggest that PAF might be
      released in the stomach by gastric epithelial cells and could be responsible for
      mucosal injury of the upper gastrointestinal tract.

PMID- 1396007
TI  - Effects of antiulcer drugs on phosphatidylcholine synthesis in isolated guinea
      pig gastric glands.
AB  - To better understand phosphatidylcholine synthesis in the stomach, we isolated
      guinea pig gastric glands and examined their [3H]choline incorporation into
      phosphatidylcholine in response to either antiulcer drugs such as
      geranylgeranylacetone (GGA) and H2-receptor antagonists or agents that cause
      phosphatidylcholine synthesis in other tissues. [3H]Choline incorporation was
      stimulated by GGA, palmitate, and 12-O-tetradecanoylphorbol-13-acetate (TPA).
      Dibutyryl cyclic-AMP had no effect. By contrast with GGA, famotidine, ranitidine,
      and cimetidine equipotently inhibited [3H]choline incorporation into
      phosphatidylcholine. GGA, palmitate, and TPA increased phosphatidyl-[3H]choline
      and decreased phosphoryl-[3H]choline as compared with control in tissues that had
      been pulsed with [3H]choline. On the other hand, no more decrease in [3H]choline
      incorporation at chase periods was observed in pulse-labeled glands in response
      to each H2-receptor antagonist. The particulate fraction of glands that had been
      incubated with GGA or palmitate had more CTP-phosphocholine cytidylyltransferase
      activity than that of glands incubated without agents. A decrease in choline
      kinase activity was not observed in the cytosolic fraction of glands that had
      been incubated with cimetidine. These results suggest that GGA and palmitate
      stimulate phosphatidylcholine synthesis by activating cytidylyltransferase, and
      H2-receptor antagonists may affect phosphatidylcholine synthesis by inhibiting
      choline uptake in the gastric glands.

PMID- 1396008
TI  - Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic
      active hepatitis in a patient with ulcerative colitis.
AB  - The simultaneous occurrence of PSC and autoimmune CAH in a patient with
      ulcerative colitis is described. Although each disease is a well documented
      complication of UC, their combination has never been reported. The diagnosis of
      PSC was based on typical findings on ERCP and liver biopsy and that of CAH was
      based on typical findings on liver biopsy supported by HLA typings and a
      remarkable response to a combination of glucocorticoids and azathioprine. The
      difficulties in establishing the diagnosis and the management of such patients
      are discussed.

PMID- 1396009
TI  - Multiple granular cell tumors of the gastrointestinal tract with subsequent
      development of esophageal squamous carcinoma.
AB  - A 52-year-old woman initially presented to our medical center with synchronous,
      submucosal tumors of the esophagus, stomach, and transverse colon. The gastric
      and colonic tumors were resected, and both displayed infiltrating sheets of
      polygonal cells with coarsely granular cytoplasm and small vesicular nuclei. The
      neoplastic cells of both tumors were immunoreactive for S-100 protein.
      Ultrastructural studies revealed the lysosomal nature of the cytoplasmic
      granules. Although the esophageal mass was not resected, it was felt that this
      represented another focus of granular cell tumor of the gastrointestinal tract.
      Two years later, she presented with disseminated squamous carcinoma of the
      esophagus. At autopsy, a submucosal granular cell tumor was found adjacent to the
      squamous carcinoma of the esophagus. To our knowledge, this is the first reported
      case of synchronous granular cell tumors that involved multiple segments of the
      gastrointestinal tract, one of which was later associated with a squamous
      carcinoma of the esophagus.

PMID- 1396010
TI  - Heterotopic bone formation in rectal carcinoma. Case report and literature
      review.
AB  - A case of heterotopic bone formation in a primary rectal adenocarcinoma was
      recently observed in a 54-year-old woman. This unusual finding was present both
      in the diagnostic biopsy and in the subsequently resected bowel. Pertinent gross
      and microscopic features are presented. This report represents the twelfth case
      in the literature of heterotopic bone formation in a primary rectal
      adenocarcinoma and the first such finding in a colonic biopsy from one of these
      malignancies. The average age of these patients was 56 years (range 32-72) and
      the male-to-female ratio was 5:7. The rectum is the most common site of
      ossification in the gastrointestinal tract. The exact mechanism of heterotopic
      ossification is unknown, but it is probably the result of metaplasia of
      fibroblasts. Adenocarcinoma has been associated with 12 of the 16 reported cases
      of rectal glandular tumors with heterotopic bone.

PMID- 1396011
TI  - Glycemic control and diabetic complications.
AB  - The relationship between glycemic control and diabetic complications remains
      unclear. Epidemiological studies reveal that approximately 25% of diabetic
      individuals do not develop complications, irrespective of degree of glycemic
      control. Studies of genetic factors, including HLA type, capillary basement
      membrane thickness, genetic predisposition to hypertension, and familial
      clustering of diabetic complications, suggest that there is a genetic component
      to developing the complications of diabetes. On the other hand, clinical trials
      have demonstrated that the progression of early, mild background retinopathy,
      microalbuminuria, and parameters of nervous system function are stabilized with
      improved glycemic control. Other metabolic parameters, such as serum lipoprotein
      levels, are significantly improved with near normoglycemia. No studies to date
      have evaluated the effect of blood glucose control on the prevention of diabetic
      complications. The degree of glycemic control required to impact on diabetic
      complications is unknown. In addition, achieving near normoglycemia carries
      increased risk for severe hypoglycemia and weight gain. Further study is needed
      to determine the long-term benefits of blood glucose control and to weigh that
      against the risks of improving glycemic control. Further investigation also is
      needed to address the probable interrelationship of genetic factors and glycemic
      control on the development of diabetic complications.

PMID- 1396012
TI  - Diabetes mellitus and macrovascular complications. An epidemiological
      perspective.
AB  - It is clearly recognized that patients with NIDDM have an increased risk for CHD.
      Recent data indicate that persons with glucose concentrations in the nondiabetic
      range also may be at higher risk for CHD. These associations may not represent
      cause and effect, however. Emerging data suggest that hyperglycemia and CHD may
      both arise from hyperinsulinemia/insulin resistance. In support of this
      hypothesis are studies showing that NIDDM and CHD have many risk factors in
      common, including age, elevated blood pressure, dyslipidemia, adiposity, and a
      central pattern of fat distribution. Moreover, these risk factors are frequent
      concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for
      NIDDM. Although the duration of NIDDM has been infrequently related to risk of
      CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance
      would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is
      a different situation. The etiological process leading to IDDM, namely the
      destruction of beta-cells in genetically predisposed persons, is not related to
      cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk
      factors for which may vary according to the location of the diseases (e.g., LEAD
      vs. CHD). There is a strong relationship between proteinuria and CVD, which has
      led to a general theory of vascular complications in IDDM based on defective
      heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts
      of this hypothesis, and the possibility is raised that a higher case-fatality
      rate in a subgroup of patients with both renal and CVD explains part of the renal
      connection, as does the general worsening of CVD risk factors.

PMID- 1396013
TI  - Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus.
AB  - In this review, we have highlighted pivotal cellular and molecular events in the
      initiation and progression of atherosclerosis. Key components of lesion
      initiation are an enhanced focal intimal influx and accumulation of lipoproteins,
      including LDL in hemodynamically determined lesion-prone areas, focal monocyte
      macrophage recruitment, intimal generation of ROS, and oxidative modification of
      lipoproteins (including LDL [Ox-LDL]). Modified lipoproteins are taken up by the
      non-downregulating macrophage scavenger receptor, with foam cell formation and
      the development of the so-called fatty streak. One transitional event in lesion
      progression is foam cell necrosis, likely attributable to the cytotoxicity of
      both intimal free radicals and Ox-LDL, with development of an extracellular
      metabolically inert lipid core. Another is the migration to and proliferation
      within the intima of medial SMCs, leading to the synthesis of plaque collagens,
      elastin, and proteoglycans. Mural thrombosis plays a significant role in the late
      stage progression of lesions. Regression of lesions is considered a function of
      the dynamic balance among components of initiation, progression, plaque
      stabilization, and removal of plaque constituents--the so-called regression
      quartet. Here, we critically examine how components of diabetes mellitus might
      impact not only lesion development, but also lesion regression. It is concluded
      that some components of diabetes mellitus augment key mechanisms in lesion
      initiation and progression and will likely retard the processes of plaque
      regression. Specifically, we focus on the various influences of diabetes mellitus
      on lipoprotein influx and accumulation, free radical generation and Ox-LDL,
      monocyte-macrophage recruitment, thrombosis and impaired fibrinolysis, and the
      reverse cholesterol transport system. The importance of nonenzymatic protein
      glycosylation in modifying a number of these processes is emphasized.

PMID- 1396014
TI  - Cell-cell interactions in diabetic angiopathy.
AB  - Normally, both ECs and mural cells, pericytes in the microvasculature and SMCs in
      large vessels of the mature vasculature, are under stringent growth control and
      remain quiescent. Regulation of vascular growth is a complex process that is
      likely to take place at multiple levels. Evidence indicates that intercellular
      communication, which may take several forms, including diffusible factors, gap
      junctions, and CAMs underlies the maintenance of normal vessels. A disruption or
      imbalance in any of these factors may be responsible for the vascular remodeling
      associated with macro/microangiopathy.

PMID- 1396015
TI  - Microalbuminuria. Implications for micro- and macrovascular disease.
AB  - Microalbuminuria is diagnosed when the UAER is greater than 20 but less than 200
      micrograms/min. The prevalence of microalbuminuria among diabetic patients is 15
      20%. Persistent microalbuminuria in diabetic patients is a risk marker not only
      of renal disease, but also of proliferative retinopathy and cardiovascular
      morbidity and mortality. Even among nondiabetic individuals, those with
      microalbuminuria tend to have an increased cardiovascular morbidity. The
      established cardiovascular risk factors, such as smoking, elevated plasma
      cholesterol, fibrinogen, and hypertension, are seen more frequently in diabetic
      patients with persistent microalbuminuria than in normoalbuminuric diabetic
      patients of similar age, sex, and diabetes duration. However, these risk factors
      cannot by themselves explain the cardiovascular overmortality in these patients.
      In addition, insulin resistance or genetic disposition to hypertension or
      cardiovascular disease fails to be the missing link. Accumulating evidence
      suggests a common pathogenetic mechanism for microalbuminuria and premature
      atherosclerosis (i.e., qualitative alterations of the extracellular matrix,
      including decreased density and sulfation of HS-PG). Decreased density of HS in
      the glomeruli may lead to albuminuria and mesangial proliferation. In the intima
      of large vessel walls, decreased density and/or sulfation of HS may enhance
      several of the processes involved in premature atherosclerosis. Diabetes affects
      the composition and structure of the extracellular matrix in many ways and leads
      to decreased density and sulfation of HS-PG by several mechanisms. Genetic
      differences in the sulfation of HS and/or genetic defects in the coordinated
      biosynthesis of HS-PG might contribute to decreased concentration and sulfation
      of HS-PG in susceptible individuals. It is hoped that susceptibility genes can be
      identified soon, thereby making prevention of severe late diabetic complications
      more successful.

PMID- 1396016
TI  - Blood pressure elevation versus abnormal albuminuria in the genesis and
      prediction of renal disease in diabetes.
AB  - A number of risk factors associated with the development of diabetic nephropathy
      has been described, such as elevated blood pressure, poor metabolic control,
      hyperlipidemia, and smoking. Abnormal albuminuria also is associated with
      progression of renal disease, but has until recently been considered principally
      a marker of disease activity rather than a risk factor. This article discusses
      the role of elevated blood pressure versus abnormal albuminuria in a genesis and
      prediction of renal disease in diabetes. Controversy exists regarding parental
      disposition to hypertension and early blood pressure elevation in the course of
      diabetes, but all studies agree that elevated blood pressure--in the presence of
      abnormal albuminuria--constitutes a risk factor. Because abnormal albuminuria is
      associated with progression disease, it may itself be a risk factor because
      increased macromolecular traffic over the glomerular membrane may produce
      glomerulopathy. Problems related to blood pressure measurement are important, and
      24-h recordings of blood pressure may be recommended in some situations.
      Regarding renal structure, preliminary results suggest that structural lesions
      precede blood pressure elevation. The solid end point for evaluation of renal
      disease progression is the fall rate of GFR, with abnormal albuminuria as an
      intermediate end point, also in drug trials. Abnormal albuminuria may constitute
      a new indication for antihypertensive treatment, being, as it is, a clear
      indicator of organ damage, whereas elevated blood pressure with normal AER may
      not increase risk substantially.

PMID- 1396017
TI  - Diabetic nephropathy. Metabolic versus hemodynamic considerations.
AB  - Not all patients with diabetes develop clinically significant nephropathy and,
      for this reason, attention has begun to focus on the risk factors for development
      of this serious complication. These risk factors have not been quantified to the
      same degree as those factors associated with more common progressive vascular
      diseases, such as atherosclerosis. However, studies of pathogenesis and clinical
      and epidemiological surveys of diabetic nephropathy point to numerous risk
      categories. Glycemic control, genetic and familial predispositions, renal and
      glomerular enlargement, glomerular hyperfiltration, and capillary and systemic
      hypertension can be invoked as contributors to this disease process. This review
      focuses on hemodynamic alterations and their role in the development and
      progression of diabetic nephropathy. Increases in GFR, largely driven by
      increases in plasma flow and capillary pressure, appear in early IDDM and NIDDM.
      This abnormality of renal vascular control probably is derived from alterations
      in several vasoactive control systems. In addition, the elevations in capillary
      pressure may be damaging to the glomerular capillaries. Arterial hypertension is
      not necessarily present before clinical nephropathy appears; however, it is a
      usual concomitant of progressive diabetic renal disease. The strongest evidences
      for the roles of altered systemic and renal hemodynamics in the progression of
      diabetic renal disease are clinical and experimental studies demonstrating
      attenuation of the disease process by lowering systemic and capillary pressures
      with antihypertensive agents, and dietary and glycemic modifications. Thus,
      although multiple factors probably interact to determine risk for the development
      of diabetic nephropathy, hemodynamic forces are a particularly important
      contributor and are especially amenable to therapeutic intervention.

PMID- 1396018
TI  - Diabetic nephropathy. Future avenue.
AB  - Diabetes mellitus has become the leading cause of ESRF in the United States.
      Patients with diabetic nephropathy suffer high cardiovascular morbidity and
      mortality. Because only 40% of diabetic patients eventually develop diabetic
      kidney disease, it may be possible to devise primary prevention measures targeted
      at the subset of patients at risk. Recently, a predisposition to hypertension, a
      family history of diabetic nephropathy, and a family history of CVD disease each
      have been associated independently with the development of diabetic renal
      complication in IDDM. Risk factors for macrovascular damage, including raised
      arterial BP, dyslipidemia, and insulin resistance, can be detected early in the
      course of progression to diabetic nephropathy. These risk indicators recently
      have been shown to be already present at the stage of normoalbuminuria in those
      patients who eventually will progress to microalbuminuria. Treatment of
      established renal disease can only delay the onset of ESRF, and lowering of
      microalbuminuria has been shown to retard the onset of persistent proteinuria.
      However, no study to date has demonstrated prevention of renal disease in these
      patients. The ultimate aim should, therefore, be the prevention of the transition
      from normoalbuminuria to microalbuminuria in individuals who are at higher risk
      of diabetic renal disease and CVD.

PMID- 1396020
TI  - Welcome to the new recruits.

PMID- 1396019
TI  - Diabetic nephropathy. Management of the end-stage patient.
AB  - Diabetic nephropathy is currently the leading cause of new patients requiring
      dialysis in the United States. Management of the diabetic patient with ESRD is
      complicated by the frequent coexistence of complications affecting other organ
      systems, including retinopathy, cardiovascular disease, peripheral neuropathy, or
      autonomic neuropathy, manifested as gastroparesis, diarrhea or obstipation,
      cystopathy, or orthostatic hypotension. Associated clinical syndromes must be
      followed and treated, if possible, while preparing the patient to receive renal
      replacement therapy. Both the clinical condition and the psychosocial environment
      are key factors in choice of ESRD therapy for an individual patient.
      Rehabilitation data are best for patients who undergo kidney transplantation, but
      these data are confounded by the fact that the healthiest patients are referred
      for this treatment modality. Living, related kidney transplant is the preferred
      initial choice for the diabetic patient with kidney disease. At most centers,
      both in the United States and abroad, the cadaveric transplant is the second
      choice for uremia therapy. At the appropriate institution, the patient with type
      I diabetes may also be considered for a simultaneous cadaveric pancreas
      transplant. While awaiting cadaveric transplantation, or if contraindication to
      transplantation is present (chronic infection, recent malignancy, or severe
      cardiac disease), diabetic patients with severe impairment of the glomerular
      filtration rate (less than 10-15 ml/min) are referred for vascular access
      placement and/or insertion of a peritoneal catheter. The decision regarding the
      choice of CAPD vs. hemodialysis must be made on an individual basis.
      Rehabilitation and survival data for these therapies are similar, although
      technique survival rates for CAPD decline dramatically as time progresses because
      of infectious complications. In-center hemodialysis has the worst survival and
      rehabilitation profile, but the sickest, most debilitated patients with the
      highest number of comorbid conditions tend to be referred for that therapeutic
      modality. Most studies of rehabilitation were performed before use of recombinant
      human erythropoietin, and comparison between ESRD treatment modalities will have
      to be reevaluated now that the drug is routinely used.

PMID- 1396021
TI  - Cytodiagnosis of lesions presenting as salivary gland swellings: a report of
      seven cases.
AB  - The cytologic and histologic findings of seven cases presenting clinically as
      salivary gland swellings are described. These included two cases of pilomatrixoma
      of skin in the parotid region, two cases of neurilemmoma in the submandibular
      area, a case of Kimura's disease in the peri-mandibular gland lymphoid tissue, a
      case of Castleman's disease in intraparotid lymph node, and a case of branchial
      cleft cyst in the parotid region. It is important to recognize lesions that
      masquerade as salivary gland tumors so that misdiagnosis and overdiagnosis on
      smears can be avoided and the patients can be treated appropriately.

PMID- 1396022
TI  - Fine-needle aspiration cytology of localized fibrous tumor of pleura.
AB  - Fine-needle aspiration (FNA) biopsy findings are presented in three cases of
      localized fibrous tumor of pleura (LFTP). Clinically, two of the tumors behaved
      benignly, although one showed frequent mitoses and foci of necrosis. The third
      tumor exhibited local aggressiveness as evidenced by rib destruction.
      Cytologically, these tumors exhibited a wide range of cellularity, composed
      mainly of small, bland oval to spindle cells with moderate numbers of stripped
      nuclei. Small bits of collagen were seen in the smears. In all cases, cell blocks
      were instrumental in making the diagnosis. Previous cytologic descriptions of the
      tumor are briefly reviewed and the cytologic differential diagnosis is discussed.
      The peripheral location of this uncommon tumor makes it an ideal target for FNA
      biopsy.

PMID- 1396023
TI  - Diagnosis of tuberculosis of bone and soft tissue by fine-needle aspiration
      biopsy.
AB  - Fine-needle aspiration biopsy is a well-established procedure in the detection of
      various neoplastic processes. However, there are only limited reports on the
      efficacy of this technique in nonneoplastic conditions. In this study, fine
      needle aspiration cytology findings of bone and soft tissue lesions in 11
      patients with tuberculosis are reported. Spine, scapula, chest wall, flank areas,
      tibia, ring, and index fingers were the sites of fine-needle aspiration biopsies.
      The age of the patients ranged from 21 to 65 years. Granulomatous reaction with
      or without caseation necrosis was seen in 73%. The aspirated material was
      acellular or predominantly composed of necrotic material and inflammatory
      infiltrates in 27%. Acid-fast bacilli (AFB) could be demonstrated in 64%. Culture
      for Mycobacterium tuberculosis was positive in 83%. This study supports previous
      suggestions that fine-needle aspiration biopsy is a simple alternative to open
      biopsy for the diagnosis of TB of bone and soft tissue lesions.

PMID- 1396024
TI  - Accuracy of diagnosis of malignant lymphoma by combining fine-needle aspiration
      cytomorphology with immunocytochemistry and in selected cases, Southern blotting
      of aspirated cells: a tissue-controlled study of 86 patients.
AB  - Fine-needle aspiration (FNA) cytology of lymph nodes in malignant lymphoma is
      fraught with difficulty. In certain clinical situations, cytology has been
      documented to be useful in patients with malignant lymphoma. The intent of our
      investigation was to determine the accuracy of a multiparameter approach in
      diagnosing lymphoma. We reviewed the results of FNA cytology combined with the
      immunocytochemistry and, in some cases, the Southern blots of aspirated cell
      suspensions obtained from 86 suspected lymphoma patients who subsequently
      underwent surgical biopsy of the aspirated site. In four cases, in which FNA was
      unable to retrieve sufficient material for diagnosis, the histology showed
      extensive fibrosis. When the FNA diagnoses were compared with the histologic
      diagnoses, the diagnosis concurred in 69 cases (56 malignant lymphomas, 12
      reactive, 1 atypical lymphoid proliferation). There was one false-positive, six
      false-negatives, and eight cases diagnosed as atypical lymphoid proliferation.
      Overall accuracy was 91%. There were two types of false-negative cases: those in
      which a diagnosis of another malignancy or unspecified malignant neoplasm was
      made and those that were diagnosed as reactive when the histology showed
      lymphoma. In seven cases, the DNA rearrangement studies of the antigen receptor
      genes were successfully performed on the aspirated cells and were useful in
      establishing lineage and clonality of both B and T lymphoid cells. Our study
      indicated that the use of a multiparameter approach in the diagnosis of malignant
      lymphoma by FNA enhanced the accuracy of diagnosis of the non-Hodgkin's
      lymphomas. In Hodgkin's disease, no benefit was derived from the approach.

PMID- 1396025
TI  - Fine-needle aspiration biopsy diagnosis of rhabdomyosarcoma: cytologic,
      histologic, and ultrastructural correlations.
AB  - A series of 15 cases of rhabdomyosarcoma diagnosed by fine-needle aspiration
      biopsy (FNAB) and confirmed by histopathology is reviewed. Cytologically, the
      tumors were composed of a variable mixture of cells, which according to the
      degree of differentiation were categorized as early, intermediate, or late
      rhabdomyoblasts. Histologically, the tumors were divided into embryonal 9,
      monomorphic round cell 4, and alveolar rhabdomyosarcoma 2. Comparison of
      histological and cytological features revealed that embryonal types were composed
      mainly of early rhabdomyoblasts. Recognition of these patterns may be helpful in
      FNAB diagnosis of rhabdomyosarcoma.

PMID- 1396026
TI  - Estrogen and progesterone receptors in cytology: a comprehensive review.

PMID- 1396027
TI  - Role of fine-needle aspiration cytology in the management of thyroid nodules:
      review of experience with 1,925 cases.

PMID- 1396028
TI  - Aspiration biopsy cytology of papillary carcinoma of the breast.
AB  - The fine-needle aspirates of two cases of noninfiltrating papillary carcinoma
      (PC) and three examples of early invasive PC of the breast were examined. In
      three cases in which the tumors displayed cuboidal or polygonal cells the
      aspirates showed papilla-like clusters of tumor cells with relatively "strong"
      cellular cohesiveness. Single and small aggregates of tumor cells as well as
      hemosiderin-laden or foamy macrophages were also present. Aspirates from the two
      PCs predominantly consisting of tall columnar epithelial cells revealed only
      monolayered and multilayered epithelial fragments with folding in one case. In
      the other case large epithelial fragments and small tight clusters of polygonal
      tumor cells were present. No bipolar nuclei of myoepithelial cells were
      identified in all cases. No specific cellular features permitting the
      differentiation between noninfiltrating and early invasive breast PCs were
      identified in this small series. Staining for carcinoembryonic antigen using the
      peroxidase-antiperoxidase technique was performed on aspiration smears of three
      cases. It revealed a positive cytoplasmic reaction in two cases.

PMID- 1396029
TI  - Epidermoid cyst of the spleen: diagnosis suggested by fine-needle aspiration
      biopsy.
AB  - The authors report a case of epidermoid cyst of the spleen, in which cytologic
      findings were characteristic and suggested this diagnosis. Histologic and
      immunohistochemical findings are described in the attempt to clarify the
      histogenesis of this cystic lesion.

PMID- 1396030
TI  - Needle aspiration cytology, immunocytochemistry, and electron microscopic study
      of unusual pancreatic carcinoma with pleomorphic giant cells.
AB  - Needle aspiration cytology, immunocytochemistry, and electron-microscopic
      findings are presented in three cases of an unusual pancreatic carcinoma in which
      pleomorphic giant cells formed an integral part of the tumour. All three patients
      were elderly males (age range 66-83 years) and had pancreatic masses. Notable
      cytologic features in all cases were the presence of bizarre mononucleated and
      multinucleated, poorly cohesive tumour giant cells, rare spindle cells, with
      occasional cannibalism and cytophagocytosis. Immunocytochemical study of
      aspirated material showed diffuse staining of cytokeratin and EMA within the
      tumour cells, while B 72.3 was seen as focal trace stain. Electron microscopy of
      aspirated material demonstrated epithelial features and these were characterised
      by the presence of tonofilaments and surface microvilli. Based on our findings,
      it is felt that the bizarre giant cells in this unusual variant of pancreatic
      carcinoma are of epithelial origin. The differential diagnosis of other tumours
      that may be associated with predominant giant cells in pancreatic aspirates is
      appropriately discussed.

PMID- 1396031
TI  - Lipomas of anterior neck simulating thyroid nodules: diagnosis by fine-needle
      aspiration.
AB  - The anterior neck is an unusual location for lipomas. Cervical lipomas can be
      mistaken for non-functioning thyroid nodules. We report eight cases from our
      files diagnosed by fine needle aspiration (FNA). Our purpose is to call attention
      to this simple technique in establishing an accurate diagnosis and how it can
      contribute to better patient management by avoiding unnecessary thyroid
      suppressive therapy and/or surgery. We advocate using FNA as the initial
      diagnostic test on palpable masses in the neck. The differential diagnosis must
      include thyroid lipomatosis, thyrolipoma or adenolipoma, amyloid goiter with
      fatty infiltration, and fat-containing thyroidal neoplasms (papillary carcinoma
      and follicular neoplasms).

PMID- 1396032
TI  - Ovarian follicular cysts: a potential source of false positive diagnoses in
      ovarian cytology.
AB  - The cytology samples of 22 benign ovarian cysts aspirated during laparoscopy (16)
      or laparotomy (6) were evaluated for clinicopathologic correlations. Clinically,
      most patients were evaluated for chronic pelvic pain. The cysts ranged in size
      from 1 to 5 cm (average 2.4 cm), and were described as having benign appearance.
      Cytologically, small granulosa cells arranged in clusters or isolated had
      granular cytoplasm with occasional microvacuoles. The nuclei were round to oval,
      uniform, and eccentrically placed. They had granular chromatin with chromocenters
      and one to two micronucleoli. Relative nuclear area averaged 50%. Mitoses were
      present in all but two cases, ranging from 0 to 38 mitoses per 10 high power
      fields (average 7.2 mitoses per 10 high power fields). Present in some cases were
      mesothelial cells and histiocytes. Three cases with follow-up histopathology
      specimens revealed two follicular cysts and a collapsed cyst without discernible
      lining. The immature appearance of the granulosa cells, the granular chromatin,
      and the presence of mitoses often suggested cytologically the possibility of a
      neoplastic process. Recognition of the cytopathology features, knowledge of the
      clinical history, and the laparoscopic findings may reassure the pathologist
      about the benign nature of the cysts.

PMID- 1396033
TI  - Processing of needle rinse material from fine-needle aspirations rarely detects
      malignancy not identified in smears.
AB  - When preparing FNA smears, we recover material left in the needle hub by
      forcefully striking the open hub against a slide. Material in the syringe tip is
      expressed by repeated forceful blasts of air (needle unattached). We investigated
      the utility of recovering additional material by rinsing the needle and syringe.
      Saline was used to flush the needle and syringe tip repeatedly. All material was
      processed by cytocentrifugation. We studied 159 needle rinse (NR) specimens from
      152 patients (breast = 70, lymph node = 30, lung = 15, soft tissue = 14, salivary
      gland = 12, thyroid = 12, liver = 5, branchial cleft cyst = 1). Malignancy was
      identified in 21 FNAs (13%) from 21 patients (14%). All were diagnosed in smears
      (9 lung, 5 liver, 4 lymph node, 2 breast, 1 soft tissue). NR material identified
      16 of these (76%). No case with benign smears (n = 138) showed malignancy in NR
      material. We conclude that if good technique is applied to preparation of smears
      and recovery of material from the needle hub and syringe tip, NR material will
      rarely identify additional malignancies. It thus represents an inefficient
      allocation of technical and human resources within the laboratory. However, NR
      may provide additional slides for special stains and may be useful for clinicians
      who do not always prepare high quality smears. Furthermore, the ease with which
      FNA of palpable masses can be repeated suggests that in the small number of cases
      requiring special stains, additional material can be readily obtained.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396034
TI  - Diagnostic value of intranuclear vacuoles in gastric leiomyoblastoma.

PMID- 1396035
TI  - Fine-needle aspiration cytology of leishmania lymphadenitis.

PMID- 1396036
TI  - AIDS: Part II.
AB  - Great strides have been made in the therapy of human immunodeficiency virus (HIV)
      infection. Currently approved drugs include zidovudine and didanosine. A third
      drug, dideoxycytidine (zalcitibine), has recently been filed for approval with
      the Food and Drug Administration. All these drugs work through inhibition of the
      reverse transcriptase enzyme. Zidovudine is the only drug that has shown clinical
      efficacy against HIV. Treatment of patients with advanced HIV disease (i.e.,
      acquired immune deficiency syndrome [AIDS] or symptomatic infection with < 200
      CD4+ lymphocytes per mm3), results in a prolongation and improved quality of
      life. Zidovudine is the only antiretroviral agent approved for the treatment of
      asymptomatic patients. Early intervention with zidovudine has been shown to delay
      progression to AIDS when patients' CD4+ lymphocyte counts decline to less than
      500/mm3, irrespective of clinical signs or symptoms of HIV infection. Didanosine
      is currently indicated for the treatment of patients with advanced HIV disease
      who are intolerant to or failing zidovudine therapy. The major toxicity of
      zidovudine is bone marrow suppression with anemia and granulocytopenia (which
      occurs in from 1% to 45% of patients, depending on the clinical stage of disease
      and the dose of the drug). Didanosine and zalcitibine have both been associated
      with a severe peripheral neuropathy, which is generally reversible on cessation
      of the drug. In addition, didanosine has been implicated as a cause of
      pancreatitis that has been fatal in a small percentage of cases. The toxicities
      of didanosine and zalcitibine range from 1% to 10%, depending on dose, duration
      of therapy, and the presence of underlying HIV-related peripheral neuropathy or a
      previous history of pancreatitis. The clinical hallmark of HIV infection is the
      development of opportunistic infections and malignancies, which are a consequence
      of the profound immunodeficiency. The risk of an opportunistic infection
      increases significantly as the T-helper lymphocyte count declines to less than
      20%, or 200 to 250/mm3. The spectrum of opportunistic infections ranges from
      viruses to protozoa. Patients with advanced HIV disease are also at increased
      risk of infection with nonopportunistic, community-acquired pathogens. Primary
      and secondary prophylaxis against the most common AIDS-defining opportunistic
      infection, Pneumocystis carinii pneumonia, is now recommended. Studies are
      currently underway to determine the efficacy of prophylaxis against other
      opportunistic pathogens. Treatment of opportunistic infections associated with
      AIDS has improved significantly over the past 5 years as new drugs and
      combination regimens of antimicrobials have been developed.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1396037
TI  - AIDS: Part I.
AB  - Acquired immunodeficiency syndrome (AIDS) is caused by infection with a
      pathogenic human retrovirus known as human immunodeficiency virus (HIV).
      Approximately 1 million people are currently infected with HIV in the United
      States, with 8 to 10 million infected individuals worldwide. The virus is
      transmitted predominantly through genital sexual contact, although orogenital
      spread has been rarely reported. Heterosexual transmission has been most common
      in the Third World, whereas male homosexual transmission has predominated in the
      United States and western Europe. Transmission through homosexual contact has
      been steadily declining over the past 5 years as transmission through illicit
      intravenous drug use and promiscuous unprotected heterosexual activity has
      increased. Sexually transmitted diseases that cause inflammatory or ulcerative
      lesions of the genital tract act as important cofactors in increasing the risk of
      transmission through sexual contact. Perinatal transmission of HIV occurs in
      approximately 30% of infants born to infected mothers. Transmission to infants
      through breast-feeding has also been documented. Health care workers have been
      infected with HIV through accidental high-risk percutaneous or mucous membrane
      exposures, albeit at a low transmission rate of 0.3%. Infection of patients by
      infected health care professionals is a rare event, having been reported only
      once in 10 years of the epidemic. Infection with HIV results in a chronic
      lifelong infection. The major targets for HIV are CD4+ T-helper lymphocytes and
      cells of monocyte/macrophage lineage. Infection of the T-helper lymphocyte
      ultimately results in the death of the cell. Over time (measured in years), a
      progressive destruction of the T-helper lymphocyte population occurs, which
      results in profound immune suppression. Infection of monocytes/macrophages is not
      cidal, but these cells do have functional alterations as a result of the
      infection, which may contribute to the immune deficiency. In addition,
      chronically infected tissue macrophages may act as an important reservoir for
      HIV, particularly in the central nervous system. Infection of the T-helper
      lymphocytes and monocytes/macrophages is mediated through attachment of HIV
      through a specific binding interaction between CD4 expressed in the plasma
      membrane of these cells and a surface glycoprotein on the virus, gp120. Once the
      virus nucleocapsid (core particle) enters the cytoplasm of the target cell, the
      viral RNA genome is reverse transcribed by a reverse transcriptase enzyme into
      proviral DNA. This proviral DNA migrates into the nucleus where it integrates
      into the host cellular genome, which results in a chronically infected
      cell.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1396038
TI  - Abstracts of the 32nd meeting of The Association for Eye Research including the
      annual meeting of the European Club for Ocular Fine Structure. Arhus, Denmark, 3
      7 July 1991.

PMID- 1396039
TI  - [Study on significance of lymphocyte chemiluminescence measurements in cancer
      patients].
AB  - Chemiluminescent responses of peripheral blood lymphocytes were measured in
      patients with carcinomas and healthy donors. The intensity of lymphocyte
      chemiluminescence (Ly-CL) in 54 preoperative patients was significantly lower
      than that in 97 healthy donors (P less than 0.05). Compared to that before
      treatment, the Ly-CL intensity in 14 patients after radiotherapy was decreased (P
      less than 0.05). However, Ly-CL intensity in 12 patients after 6-8 days of
      thymosin therapy was significantly increased (P less than 0.05), and exceeded
      that of healthy donors (P less than 0.01). These data suggest that Ly-CL
      measurements may become a new method for monitoring lymphocyte activity or
      function, and evaluating therapeutic effectiveness in cancer patients.

PMID- 1396040
TI  - [Characteristics and biologic significance of changes in DNA content of rat liver
      cells during hepatocarcinogenesis].
AB  - DNA content of hepatocellular carcinoma (HCC) induced by diethylnitrosamine
      (DENA) in Wistar rats was quantitatively measured using flow cytometry. In normal
      adult rats, hepatocytes with tetraploid (4C) DNA content constitute the major
      cellular population (72.1%), whereas diploid (2C) hepatocytes were of a quite
      small number (16.9%). Under the persistent effect of DENA, the atavistic
      proliferation of 2C hepatocytes was obviously increased at the cirrhotic stage,
      which followed the pre-cirrhotic stage, and replaced 4C hepatocytes to become the
      major cellular population. HCC at its early cancerous stage was characterized by
      predominated of DNA 2C cells, and HCC at its progression stage showed a selective
      and advantageous growth of aneuploid(AN) stemline cells. The whole
      hepatocarcinogenesis course showed a change of DNA stemline from 4C to 2C to AN,
      which might be the essential biologic kinetic mechanism of the development and
      progression of HCC. It is also suggested that HCC at early and progression stages
      are characterized by predominance of DNA 2c and AN hepatocytes.

PMID- 1396041
TI  - [Prognostic significance of DNA content in transitional cell carcinoma of the
      urinary bladder].
AB  - The cellular DNA content in paraffin-embedded specimens of recurrent transitional
      cell carcinoma of the urinary bladder were analyzed by quantitative image
      analysis in 48 and flow cytometry techniques in 44 cases. The results showed a
      positive correlation of cellular ploidy with malignant proliferation of the
      tumors. The aneuploidy was increased in cases of higher clinical stages and
      histological grades. The prognosis of patients with diploid cells was better than
      those with aneuploidy, while patients with aneuploidy and higher grading showed
      very poor prognosis. The recurrence rate of diploid tumors was considerably lower
      than that of aneuploid tumors. The results indicate that such a correlation might
      be of clinical significance in prognosis and predicting and controlling
      recurrence of tumors.

PMID- 1396042
TI  - [Fusarin C induced esophageal and forestomach carcinoma in mice and rats].
AB  - Fusarium moniliforme, a fungus of established carcinogenic potential, is one of
      the most common fungal contaminants of maize, millet and other grains in Linxian,
      China, a high-risk county for human esophageal cancer. Fusarin C, a major product
      of F. moniliforme grown on corn in the laboratory, is mutagenic in Salmonella
      tester strains and in V79 cells. Fusarin C treated rat esophageal epithelial cell
      line showed several characteristics of malignant transformations including the
      growth in nude mice. The present work demonstrated that Fusarin C can induce
      esophageal and forestomach carcinoma in DBA mice and Wistar rats thus further
      substantiating the carcinogenicity of this mycotoxin.

PMID- 1396043
TI  - [Expression of c-myc and c-ki-ras oncogene in human pancreatic carcinoma].
AB  - Using Northern blot technique, the oncogene expression in normal pancreatic
      tissue and human pancreatic carcinoma PC-2 and PC-3 cell lines was studied. Four
      oncogene probes (c-N-ras, c-ki-ras, c-myc and c-fos) consisting of recovered
      endonuclease digested fragments were nick translated. After hybridization and
      autoradiography, none of the four oncogenes was expressed in the normal human
      pancreatic tissue, but the human pancreatic carcinoma PC-2 and PC-3 cell lines
      expressed the c-myc and c-ki-ras genes. Their transcripts were 2.7 and 6.0 kb,
      respectively. Expression of the other two oncogenes (c-N-ras and c-fos) was not
      detected. The results of this study together with those reported in the
      literature verify the fact that the expression of c-myc and c-ki-ras oncogenes
      may play a very important role in the development of human pancreatic carcinoma.

PMID- 1396044
TI  - [Effect of hematoporphyrin derivative (HPD) plus light on DNA repair synthesis
      and enhancement of HPD photosensitization by vitamin C in mouse hepatoma].
AB  - There are only a few reports in the literature on photodynamic effects of HPD on
      gene expression and the repair of DNA damage. Previously, we suggested that
      nuclear transcription activity was markedly suppressed by HPD plus light. In this
      study, we investigated the photodynamic effect or DNA repair synthesis as
      measured by unscheduled DNA synthesis (UDS) in hepatoma cells. The results
      indicated that DNA repair capacity was greatly inhibited by HPD plus light. When
      hepatoma cells were pretreated with HPD of different concentrations and then
      exposed to the same light dose, significant inhibitions of UDS over control were
      seen and appeared in a dose-dependent fashion. In addition, while hepatoma cells
      following the exposure to HPD of the same concentration were irradiated with
      different time, the UDS was markedly decreased as the duration of irradiation was
      prolonged. However, no changes were observed when either HPD or light was used
      alone. The present study also included an experiment to determine whether HPD
      combined with vitamin C gives an enhanced photosensitization. It was found that
      vitamin C significantly potentiated the suppressing effect on DNA repair
      synthesis.

PMID- 1396045
TI  - [Estimating cancer latency using data from a case-control study with time-related
      factors. I. A general multivariate theory and algorithm].
AB  - In the present paper, a general multivariate approach, estimating cancer latency
      using data from a case-control study with time-related factors, is proposed based
      on the theory for risk analysis of states. Making use of a forward-analysis and
      backward-synthesis strategy and excess exposure fraction, this approach can
      simultaneously accomplish multivariate logistic regression analysis and
      estimation of susceptible exposure ages and latency distribution. The latency is
      resolved into a accumulative period and preneoplastic period. It gives a
      theoretical interpretation for primary and secondary prevention of cancer.

PMID- 1396046
TI  - [Influence of dietary selenium level on immune function of rats with esophageal
      tumors induced by methylbenzylnitrosamine (NMBzA)].
AB  - The influence of dietary selenium of the incidence of esophageal tumor induced by
      NMBzA and the immune function during carcinogenesis were studied in rats fed with
      Torula yeast diet and survived for 18 weeks. The incidences of esophageal tumors
      were statistically not significant among rats on normal, high and low selenium
      intake (P greater than 0.05). The level of plaque forming cells (PFC), delayed
      type hypersensitivity (DTH), natural killer cell activity (NK) were significantly
      higher in the high selenium diet group than those of the low selenium diet group
      (P less than 0.05). The authors believe that the modulation of dietary selenium
      can alter the immune function of animals during carcinogenesis but the
      anticarcinogenic effect of selenium still needs further study.

PMID- 1396047
TI  - [Pharmacokinetic study of pseudohainanensine with deuteriumlabeled analogue as
      internal standard].
AB  - Pseudohainanensine (HH08) is a synthetic compound which is active against L-1210.
      In order to study the pharmacokinetic characteristics of this compound in rats,
      3', 4'-dideuteropseudohainanensine (DH08) was synthesized and used as internal
      standard in GC-MS determination for quantitative analysis of alkaloid HH08 in the
      blood of rats that had been given HH08 at a dosage of 10 mg/kg intravenously.
      Experiments demonstrated that the detection limit of HH08 was 3 micrograms/ml and
      the peak concentration in the blood was 13.1 +/- 0.2 micrograms/ml after a single
      intravenous injection (one min. after injection). The biological half life time
      can be divided into two phases; the fast phase (alpha) 2.61 min, and the slow
      phase (beta) 42.59 min. Two hours after the injection no drug could be detected
      in the blood.

PMID- 1396048
TI  - [Spectrum distribution of ultra-weak luminescence of blood in lung cancer
      patients].
AB  - Using the single-photon counting detecting system manufactured by the Institute
      of Biophysics, Academia Sinica, the emission spectrum of ultra-weak luminescence
      of blood from 10 normal blood donors and 37 lung cancer patients were studied.
      The experimental results showed that ultra-weak photon emission of patients' was
      originated from the red region and three emission peaks were observed at 425-460,
      535-595 and 620-660 nm. The intensity of photon emission at 425-460 nm of
      patient's blood was markedly higher than that of normal blood donors, with
      statistical significance. Furthermore, after operation, the spectrum distribution
      almost returned to that of what was seen in normal blood donors. Our observation
      shows that ultra-weak luminescence of blood may serve as an early detection of
      lung cancers.

PMID- 1396049
TI  - [Immunohistochemical analysis of physicochemical properties of target antigens
      with anti-tumor monoclonal antibodies].
AB  - A new simplified assay for the identification of physicochemical nature of the
      antigen recognized by monoclonal antibodies (MAbs) against tumor using direct
      immunohistochemical methods of avidin-biotin peroxidase complex (ABC) is first
      described. The experimental results demonstrate that this method does not need to
      purify the target antigens or special equipment, but is as specific and sensitive
      as immunoblotting technique. For these reasons, this procedure is much simpler
      and less expensive than the methods previously published. This method may thus be
      useful to investigate the properties of antigens to which MAbs are directed.

PMID- 1396050
TI  - [Clinical multivariate statistical analysis of nephrotoxicity induced by
      cisplatin].
AB  - Nephrotoxicity was studied in 47 patients who received combined chemotherapy with
      cisplatin (DDP, 50-100 mg/m2) as the chief agent. The treatment was given every 3
      4 weeks with vigorous hydration and forced diuresis. The renal tubular toxicity
      was evaluated by urinary beta 2 microglobulin (beta 2-MG). It was found that the
      nephrotoxicity secondary to DDP was dose-dependent. Hypertonic saline was able to
      decrease the renal damage without any significant difference among the first,
      second and third course. The nephrotoxicity of DDP administered in one day was
      more severe than that given in two days. beta 2-MG was a good parameter of DDP
      nephrotoxicity. By multivariate statistical analysis, metoclopramid and
      chlorpromazine were found to alleviate DDP nephrotoxicity. Classification,
      examination and management of DDP nephrotoxicity is proposed.

PMID- 1396051
TI  - [Clinical pharmacokinetics of cis-diamminedichloroplatinum (DDP)].
AB  - We studied the pharmacokinetics of DDP in 9 cancer patients who received iv
      infusion of DDP (100-120 mg/m2). Platinum concentration was measured by high
      performance liquid chromatography (HPLC). Plasma clearance of platinum was
      biphasic. There was a short initial phase with a half life of 19.8 min and a long
      second phase with a half life of 41.13 hours. A small peak was noted in 5 hours
      after the end of DDP infusion in about 50% of patients. This suggested tissue
      reabsorption, release and entero-hepatic circulation. Plasma ultrafiltrable
      platinum concentration fell with a half life of 21 min. Nearly 75-96% of the
      platinum in the plasma was protein bound 24 minutes after DDP infusion. The
      urinary excretion of platinum was found to be 9.52-21.35% in 24 hours with 6.69
      19.57% eliminated within the first three hours.

PMID- 1396052
TI  - [Mechanism of cloned human lymphokine-activated killer (LAK) cells killing human
      leukemia cells in vitro].
AB  - The killing of human leukemia cells by cloned human LAK cell was investigated
      with 51Cr release, semisolid agar colony-formation and MTT assay. Human LAK cells
      were generated and cloned from normal peripheral blood mononuclear cells
      stimulated with IL-2. Cloned LAK cells showed significant cytotoxicity against
      human erythroleukemia cell line K 562, promyelocytic leukemia cell line HL 60 and
      T-lymphoblastic leukemia cell line Jurkat in standard 4-hr 51Cr release assay and
      the lytic percentage were 67.1%, 58.4% and 53.1% with E/T ratio of 40:1.
      Moreover, cloned LAK cells could also inhibit the 6-day spontaneous colony
      formation of K 562 and HL 6 C cells in semisolid cultures when the LAK cells were
      preincubated with target cells for 4 hours in liquid medium at 37 degrees C. The
      degree of colony inhibition was 91% for K 562 and 96% for HL 60, which was
      quantitatively greater than that determined by 51Cr release at the same E/T ratio
      of 40:1. In addition, with MTT assay, cytotoxicity of supernatant of cloned LAK
      cells 3 days in culture against K 562 and HL 60 cells was observed. Our data
      indicated that cloned human LAK cells could kill both human leukemia cells and
      their stem cells and the mechanism may involve direct lysis and/or inhibition
      mediated by LAK cells and indirect inhibition of some soluble factors released
      from LAK cells.

PMID- 1396053
TI  - [Nuclear morphometry and DNA cytometry in the grading of malignant tumors of the
      salivary gland].
AB  - Nuclear morphometry and DNA cytometry were performed in 6 normal salivary glands
      and 37 malignant tumors of the salivary gland. Multivariate discrimination
      analysis was used to grade the malignant salivary gland tumors. The
      discrimination rate was 100% for normal salivary gland, benign tumor, high
      malignant carcinoma and low malignant carcinoma. It was 66.7% for borderline
      malignancies. These results indicate that quantitative cytological analysis is
      effective and reproducible in the grading of salivary gland tumors. Stepwise
      multivariate regression analysis showed that there was a very complicated
      correlation between DNA content and nuclear morphometric parameters of salivary
      gland tumors.

PMID- 1396054
TI  - [Relationship among expression of HLA antigen, cell ploidy and metastasis in
      human colorectal cancer].
AB  - HLA antigen expression, cell ploidy determined by DNA content with flow
      cytometry, and tumor metastasis were analysed and studied in 51 cases of human
      colorectal cancer samples. It was observed that the pattern of HLA expression and
      lymph node metastasis varied significantly when the cancer cells were categorized
      into distinct ploidies. For tetraploid cancer cells, the percentage of positive
      expression of class I and II antigens were all 90.0% with no detectable
      metastasis. On the contrary, the expression of class I and II antigens were as
      low as 13.3% and 40.0% with metastasis in 26.7% of the samples from diploid
      group. or 20.0% and 40.0% with a metastasis percentage of 60.0% for heteroploid
      group. The relevant patterns for triploidy and aneuploidy were between the above
      three groups. The significance of the unexpected low metastasis of the tetraploid
      cancer cells both in clinical prognosis and mechanism studies is further
      discussed.

PMID- 1396055
TI  - [Biologic effects of Tween 80 in combination with hyperthermia on human stomach
      cancer cell line BGC-823].
AB  - Cells of human stomach cancer cell line BGC-823 were treated with Tween 80 and
      hyperthermia 39 degrees C to 43 degrees C for 20 to 100 minutes. Normal human
      fibroblasts and mitomycin C were used as controls. The results showed Tween 80
      greatly reduced the activation energy of BGC-823 cells. Synergistic effect was
      observed if applied with heat 39 degrees C. With the increase in temperature and
      time, the inhibitory effect on the cancer cells was gradually intensified. The
      lethal rate of heat 41 degrees C associated with Tween 80 was 5.2 times as that
      of heat alone. The inhibitory effect of heat 41 degrees C for 100 minutes
      combined with Tween 80 was equivalent to 43 degrees C for 100 minutes. In other
      words, the heat critical Temperature of BGC-823 cells was reduced about 2 degrees
      C. The measurement of membrane fluidity, SDH activity and the rest also showed
      heat 41 degrees C produced the highest synergy with Tween 80. The specific and
      sustained action exceeded that of mitomycin C. The response of the normal cells
      was mild and reversible. These studies suggest that the synergistic mechanism of
      Tween 80 and hyperthermia possibly lies on the cell plasma membrane system.

PMID- 1396056
TI  - [Morphometric study on nasopharyngeal carcinoma (NPC)].
AB  - Morphometric parameters of carcinoma cells in 78 NPC and columnar epithelium
      basal cells in 21 of these 78 NPCs were measured by Quantimet 520 analyser. The
      results showed that: 1. Prominent enlargement of nuclei was a pathognomonic
      feature of carcinoma cells, except small spindle carcinoma cells, as compared
      with the normal basal cells, 2. vesicular nucleus cell carcinoma and small
      spindle poorly differentiated squamous carcinoma had their own characteristic
      morphometric parameters as compared with those of the ordinary poorly
      differentiated squamous carcinoma, and 3. there was no significant morphometric
      difference between vesicular nucleus cell carcinoma and poorly differentiated
      adenocarcinoma.

PMID- 1396057
TI  - [Significance of typing in the survival of malignant lymphomas].
AB  - The significance of typing and subtyping in the survival rate of 116 patients
      suffering from pathologically proved malignant lymphoma is presented. Our data
      show that Hodgkin's disease was least malignant, having the highest survival
      curve (P less than 0.005). Lymphoblastic lymphoma had the highest degree of
      malignancy, having the lowest survival curve. Yet, the middle portion of its
      curve resembled that of the peripheral T cell lymphoma. Although the degree of
      malignancy and the curve of peripheral T cell lymphoma and B cell lymphoma were
      similar (0.05 greater than P greater than 0.05), their middle portion were
      separated, a fact worthy of further study. Typing of malignant lymphomas is of
      practical importance.

PMID- 1396058
TI  - [In vitro effect of catechin on cell growth].
AB  - Experimental study on the effect of catechin, an extract of Chinese green tea, on
      cell growth of HeLa, KB and 3T3 cell lines and its possible mechanism are
      reported. The proliferative survival curves showed that HeLa and KB were
      sensitive to catechin, while 3T3 was less so. The survival curve of HeLa cells
      treated with catechin varied with the dose and duration of exposure. 3H-TdR
      incorporation rate into HeLa cells was inhibited by catechin and the inhibition
      rate was also dose and exposure dependent. It suggests that one of the mechanisms
      of cell growth inhibition by catechin may probably due to inhibition of DNA
      synthesis.

PMID- 1396059
TI  - [Immunohistochemical diagnosis in fine-needle aspiration cytology].
AB  - This paper reports 25 kinds of polyclonal or monoclonal antibodies by ABC
      immunohistochemical technique used for 253 cell smears by fine-needle aspiration.
      The results were: 1. Immunohistochemical diagnosis were classified into 136
      metastatic cancers (K12+ EMA+ CEA+ LCA-), 92 lymphomas (LCA+ K12- EMA- CEA-), 4
      mesenchymal tumors (Vimentin+), 3 melanomas (S-100+ NSE+), 15 reactive
      proliferations (K+ lambda+ CD4+ CD8+) and 3 unspecified. 2. The origin of 70
      metastatic cancers were classified into 36 lung (HLC3-AB+), 4 gastrointestinal
      tract (MG7+), 8 thyroid (TGB+), 1 prostate (PSA+), 3 liver (AFP+) and 14 unknown.
      3. Immunologic phenotype of 87 lymphomas were classified into 66 cases of B-cell,
      4 T-cell, 3 histiocyte, 7 Hodgkin's diseases and 7 unclear. The above results
      suggest that immunohistochemical method may be used as a new method of diagnosing
      and differentiating epithelial and non-epithelial tumors, detecting primary focus
      of metastatic cancer, differentiating between reactive proliferation and lymphoma
      and specifying immunologic phenotype of lymphoma in cell smears of fine-needle
      aspiration.

PMID- 1396060
TI  - [Histogenesis of esophageal carcinoma].
AB  - Histopathologic and tritiated thymidine labelled autoradiography was carried out
      on 206 human esophageal biopsy specimens obtained in Linxian county, a high risk
      area of esophageal cancer in China. According to the histopathologic criteria, 6
      cases showed atrophy, 151 normal, 31 hyperplasia, 14 dysplasia and 4 carcinoma.
      The index of labeled cells were: atrophy 3.3, normal 4.73, hyperplasia 4.9,
      dysplasia 5.6, carcinoma in situ 11.76 and invasive carcinoma 24.63. Significant
      increase in labeling was found in the esophageal mucosa with hyperplasia,
      dysplasia and carcinoma. There was a gradient of increased expansion in the basal
      layer as the proliferating cells progress from normal to hyperplasia, to
      dysplasia, and to carcinoma. These results show that the hyperplastic and
      dysplastic cells were fundamental phases of carcinomatous change in the
      esophageal mucosa. It shows a wide spectrum of cellular alterations in the course
      of malignant change and the close relationship between the morphological
      alterations and cell biology.

PMID- 1396061
TI  - [Clinico-pathologic analysis of 60 patients with primary malignant lymphoma of
      the small intestine and mesentery].
AB  - Clinico-pathologic analysis of 60 patients with primary malignant lymphoma of the
      small intestine and mesentery is presented. It occurs mainly in the adult. Both
      of these two tumors were first presented by abdominal pain and mass. Secondary
      anemia was common. They were complicated by intestinal obstruction, perforation
      or intussusception. The prognosis was aggravated by a large tumor mass, advanced
      stage and pathology of diffuse large cell subtype. Combined surgery, chemotherapy
      and radiotherapy were effective.

PMID- 1396062
TI  - [20 rare primary hepatic malignant tumors].
AB  - We collected 20 primary liver malignant tumors other than hepatocellular
      carcinoma from 1968 to 1990; sarcomas from mesenchymal tissue (hepatic
      leiomyosarcoma, hepatic fibrosarcoma, Kupffer cell sarcoma, hepatic lymphatic
      sarcoma), two subtypes of hepatocellular carcinoma (fibrolamellar carcinoma and
      clear cell carcinoma), hepatic carcinoid, squamous carcinoma, etc. Analysis with
      review of literature is given.

PMID- 1396063
TI  - [Surgical treatment of rectal carcinoid--report of 60 cases].
AB  - From 1973 to 1989, 60 patients with rectal carcinoid, as discovered by mass
      screening, were treated. It accounted for 0.02% of subjects screened and was the
      first among all G-I carcinoids. 96.7% of patients were asymptomatic and 86.6%
      were located within 8 cm of the anus. All were treated by surgery and none has
      died of this disease. The frequency of positive stump was 27% as observed in 31
      specimens by local resection. Extended local resection still gave a positive
      residual rate of 9.4%. The authors believe that extended local resection is
      indicated even for small lesions less than 0.5 cm across.

PMID- 1396064
TI  - [Pain-relief effect of tramadol HCL capsule for moderate and severe cancer pain].
AB  - Fifty-one patients with moderate (11/51) and severe (40/51) cancer pain were
      given a new non-narcotic analgesic -Tromadol HCL capsule (THC). In 42 of these
      patients, partial relief was obtained with an average relief time (ART) of 4.1
      hours. The average starting time was 58 minutes. Pain relief rate (PRR) in
      moderate and severe pain was 82% (P = 0.945), and the ARTs were 7.4 hr. and 3.2
      hr., respectively (P = 0.005). In 43 patients who were entered into a randomized
      study with control drugs of AT-237 (36 cases) or Anfendein (7 cases), the PRR was
      60.4% (26/43), ART was 1.3 hours. The PRR and ART of THC and control drugs were
      statistically significant (P less than 0.001 and P = 0.023). Within adequate dose
      range, increase of THC dose could improve its analgesic effect (P = 0.011). The
      main side-effects were: somnolence (37.3%), nausea (35.3%), dizziness (33.3%),
      palpitation and anorexia (25.5%) and constipation (9.8%) which did not
      necessitate the suspension of THC administration.

PMID- 1396065
TI  - [Five years' experience on intracavitary afterloading technique for carcinoma of
      the uterine cervix].
AB  - A series of 152 patients with carcinoma of uterine cervix treated from 1983-1984
      by 3-channel (Cs-137) Buchler afterloading is presented. There were 1 Stage I, 89
      Stage II (58.55%), 60 Stage III (39.47%) and 2 Stage IV lesions. The dose rate at
      point A was 10-25 cGy/min. The isoeffect correction factor of the afterloading
      and conventional methods at point A was 0.625. The over-all 5-year survival rate
      of the whole series was 70.39%, with 77.53% for Stage II and 61.67% for Stage III
      lesions. The frequency of late rectal and bladder reactions were 9.21% and 7.89%,
      respectively. It should be pointed out that the dose rate at the point 2cm from
      the external os was 1.7-8 times as high as that at point A, which caused more
      severe reactions in the surrounding tissues. A suggestion of reducing the number
      of fractions of intracavitary afterloading irradiation, the dose at point A
      delivered from vaginal irradiation and adopting partial whole pelvic external
      irradiation is put forward by the authors.

PMID- 1396066
TI  - [Diagnosis and treatment of lung cancer in Shanghai--an analysis of present
      status].
AB  - The status of diagnosis and treatment of lung cancers as discovered in one year's
      interval in the Shanghai population is presented. A total of 940 lung cancers was
      detected from inhabitants 35-64 years of age, with a male-female ratio of 1.8:1.
      Pathology showed 35.7% adenocarcinoma and 35.1% squamous cell carcinoma. There
      was a predominance of adenocarcinoma (47.6%) in the female and squamous cell
      carcinoma (44.6%) in the male. Most (68.6%) of the lesions detected were already
      advanced in contrast to 14.7% of Stage I disease. The necessity of the doctor's
      vigilance was demonstrated by the fact that 23.3% of patients was seen by the
      doctor within one month after the presenting symptom and 44.5% of them had their
      diagnosis made within one month after their first hospital visit. The treatment
      consisted of surgery for 33.3%, chemotherapy for 35%, traditional Chinese
      medicine for 20% and symptomatic management for 9.7% of patients. As only 55.8%
      Stage I patients was treated by surgery, the protocol of treatment seemed to be
      improperly biased. Adequate training of the health workers was shown by the fact
      that 79.7% of these patients was confirmed by pathology and/or cytology and most
      of the Stage I lesions were diagnosed outside the hospital.

PMID- 1396067
TI  - [Interventional radiology guided regional infusion chemotherapy for pelvic
      malignancy].
AB  - Retention transcatheter in the deep branch of femoral artery introduced by the
      Seldinger technique combined with the original arterial infusion was used in
      patients with pelvic malignancy. Infusion of chemotherapy and/or arterial
      embolization under the guide of pelvic arteriography was given. No 4-7 preshaped
      radiopaque catheter was passed from the femoral artery deep branch to the lower
      abdominal aorta. By turning the catheter tip and moving it up and down under TV
      monitor, it can be slipped into the uterine artery and/or common hepatic artery
      which supply blood to the tumor mass. Ten patients, including 7 with persistent
      or recurrent tumors, 2 with liver metastasis and 1 with vaginal botryoidies were
      treated. The immediate results were satisfactory in most patients with relief of
      symptoms and partial reduction of tumor. No side effects or complications were
      noted.

PMID- 1396068
TI  - [Clinico-pathologic study of resection of low rectal cancer with preservation of
      anus--report of 48 patients].
AB  - Fourty-eight patients suffering from low rectal cancer were treated from 1987
      1989 by operation with preservation of anus. Thirty-six similar patients as
      treated by Mile's operation during the same period served as controls. Follow-up
      results showed that recurrence developed earlier and in higher frequencies in the
      former group. The frequencies of recurrence in those with anus preserved were: 1
      year 42% (5/12) and 2 years 50% (6/12) whereas those of Mile's operation were: 1
      year 3% (1/36) and 2 years 11% (4/36) (P less than 0.01). The 1-year mortality
      rates also differed conspicuously: former group 17% (2/12) and the latter group
      3% (1/36). The authors believe that for lesions of Dukes' B or C stages,
      pathological moderate or poor differentiation, larger than 4 cm across, deep
      crater or presence of peri-rectal or lymph node involvement as discovered on
      exploration should not be treated by resection with preservation of anus.

PMID- 1396069
TI  - [Overexpression of p53 protein in human spontaneous esophageal carcinoma and
      fetal esophageal carcinoma induced by N-methyl-N-benzylnitrosamine (NMBzA)].
AB  - In normal cells, p53 protein is virtually undetectable by immunohistochemical
      methods. Mutation of p53 gene results in overexpression of the protein and thus
      levels of p53 detectable by immunohistochemistry may indicate expression of the
      mutant form of p53. Esophageal cancer (EC) samples obtained from patients who had
      undergone surgery were assayed for expression in p53 protein. Among 18 primary EC
      and their adjacent tissues, 7 cases of EC and 5 adjacent tissues overexpression
      of p53 protein was detected immunohistochemically. In cases with overexpression
      of the p53 in the adjacent tissues was detected 4 were also positive in the
      carcinomas. These results suggest that overexpression of p53 protein is a common
      molecular event in EC and may occur in the early stage of esophageal
      tumorigenesis. In addition, we found over expression of the p53 protein in the
      human fetal esophageal carcinoma induced by NMBzA, indicating that p53 gene
      mutation (s) might have occurred. The results provide further evidence that N
      nitrosamine is a causative agent of human esophageal cancer.

PMID- 1396070
TI  - [Detection of interferon-gamma in malignant peritoneal effusion in ovarian cancer
      patients].
AB  - Concanavalin A-induced human and mouse T cell proliferation assay was used to
      detect the suppressive activity of ascitic fluid (AF) in ovarian cancer patients.
      About 80% of AF specimens were found to be suppressive. However, when later
      tested for AF's effect on NK cell activity, instead of suppression, marked
      enhancement was observed. As IL-2 was barely detectable in AF, attention was
      focused on interferon (IFN). Its presence was then examined and confirmed by the
      ability of AF to protect HEp-2 cells from the cytopathic effect of vesicular
      stomatitis virus (VSV). As the protective effect against VSV was abolished by low
      pH treatment and by anti-human interferon gamma monoclonal antibodies (MAb), the
      IFN identified in AF was of the gamma type (IFN-gamma). The MAb could markedly
      inhibit not only AF's NK-enhancing effect but T cell suppressing effect as well.
      After removal of the IFN-gamma from AF by affinity chromatography, both
      activities of AF were lost. The possible clinical implication of this new finding
      with regards to host's anti-tumor resistance and prognosis is discussed.

PMID- 1396071
TI  - [Experimental study on IL-6 activity against tumor: I. Regulation of IL-2-induced
      LAK cells].
AB  - The ability of human recombinant interleukin-6 (IL-6) to regulate the induction
      and function of lymphokine activated killer (LAK) cells from human fetal spleens
      was studied. The results showed that IL-6 alone was unable to induce fetal
      splenic mononuclear cells (FSMC) to develop functional LAK cells, nor was it able
      to affect the number of IL-2-induced LAK cells and to alter the lytic activity of
      the induced LAK cells in effector phase. However, when IL-6 was used in
      combination with IL-2 during the induction phase, the resulting LAK cells
      displayed considerably greater lytic activity than that with IL-2 alone (P less
      than 0.01), and this effect was IL-6 dose-dependent. The possible mechanism of
      the synergetic effect of IL-2 and IL-6 in LAK cell induction from human fetal
      spleens is discussed.

PMID- 1396072
TI  - [Experimental expansion and antitumor effects of LAK cells from cancer patient's
      peripheral blood].
AB  - To augment the in vitro expansion of LAK cells, we added highly purified human
      recombinant interleukin-2, phytohemagglutinin and accessory cells (Uc cells) to
      the LAK culture system, with which huge number of LAK cells (LAK-L) were
      generated from originally small number of peripheral blood lymphocytes of cancer
      patients. These LAK-L cells exhibited similar antitumor activities in vitro and
      in vivo, as compared with LAK-S cells (LAK cells activated in short term
      culture). The phenotyping results suggested that there was more expression of IL
      2 receptors in the LAK-L group than in the LAK-S group. The rapid proliferation
      of LAK-L cells was characterized by the expansion of OKT8 positive cells in the
      LAK-L populations.

PMID- 1396073
TI  - [Detection of point mutations of C-Ki-ras oncogene in colon cancer by PCR using
      specific oligonucleotide probes].
AB  - Activation of C-Ki-ras oncogene by point mutation within codon 12,13 was
      determined by Polymerase Chain Reaction (PCR) using specific oligonucleotide
      probes. In 9 of 42 colon cancer specimens point mutations in codon 12 of C-Ki-ras
      oncogene were found. The point mutations identified were GGT(Gly)----GAT(Asp) (4
      cases), GGT (Gly)----TGT (Cys) (3 cases) and GGT(Gly)----GTT(Val) (2 cases),
      respectively. Two types of point mutations (GGT----GAT, GGT----TGT) were found
      simultaneously in one specimen. The results showed that there was no relationship
      between the point mutation of C-Ki-ras oncogene and patient's sex, age, state of
      metastasis or prognosis.

PMID- 1396074
TI  - [Action of calmodulin antagonist on the proliferation and cytoskeleton of A549
      lung cancer cells].
AB  - Trifluoperazine (TFP) could inhibit the proliferation of A549 lung cancer cells
      and human embryo lung (HEL) cells. The inhibitory effects were dose dependent.
      The inhibitory effects were stronger in A549 lung cancer cells than in HEL cells
      at the same TFP dose. Cytoskeleton in A549 lung cancer cells treated with TFP was
      increased as observed electron microscopically. The role of calmodulin in the
      proliferation and the changes in cytoskeleton of A549 lung cancer cells is
      discussed.

PMID- 1396075
TI  - [Anti-emetic effect of ondansetron in cisplatin induced nausea and vomiting--a
      randomized clinical trial].
AB  - The anti-emetic effect of ondansetron in cisplatin induced nausea and vomiting
      was studied in a randomized cross-over trial in 52 patients. The dose of
      cisplatin was 80-120 mg/M2 iv drip given in 1-3 days. The patients randomly
      received ondansetron or our routine anti-emetic regimen in the first cycle of
      chemotherapy. All the patients were crossed-over to the other anti-emetic regimen
      on the second cycle of the same cisplatin containing regimen. The results showed
      that ondansetron was superior to our routine anti-emetic regimen in controlling
      acute nausea and vomiting. 86% of patients treated with ondansetron and 20.4%
      treated with the routine regimen had a complete or marked response (O-2 emetic
      episodes). The mean frequency of vomiting were 1.3 times in ondansetron and 8.0
      times in the routine regimen (P less than 0.01). Control of delayed emesis was
      comparable in the two arms. No patient had neurological symptoms in the
      ondansetron group whereas 4 patients in the routine group had extrapyramidal
      symptoms.

PMID- 1396076
TI  - [Hepatic arterial infusion chemotherapy plus embolization for unresectable liver
      cancer--a report on 40 patients].
AB  - Forty patients with unresectable liver cancer were treated by hepatic arterial
      infusion chemotherapy plus embolization (HAI+HAE). Thirty-four patients had huge
      masses and 6 nodular lesions. After HAI+HAE, the frequency of greater than or
      equal to 50% reduction in tumor size was 67.5% (27/40); that of reduction in
      marked and partial disappearance of tumor blood vessels was 90% (36/40); and that
      of marked decrease and normalized AFP was 90.3% (28/31). The mean survival of 12
      patients treated solely by HAI plus HAE was 17.2 months, and one of them has been
      alive for 48 months. Twenty-eight patients became operable following HAI+HAE and
      26 of them underwent hepatic resection. Pathologic examination revealed obvious
      necrosis in most part of the tumor with a few viable cancer cells in the
      periphery and inflammatory reaction as well as fibrotic proliferation around the
      necrotic tumor tissue. The authors believe that hepatic arterial infusion
      chemotherapy plus embolization for the unresectable liver cancer is effective. If
      satisfactory shrinkage of the tumor is observed, subsequent resection should be
      contemplated for cure.

PMID- 1396077
TI  - [Treatment of proximal biliary duct carcinoma].
AB  - During the past 30 years, 21 patients suffering from proximal biliary duct
      carcinoma were treated by surgery. The resectability rate was 14%. Three patients
      had radical resection, 2 surgical bypass, 3 surgical catheterization for
      drainage, 4 PTCD, and 2 intraluminal radiotherapy with Iridium-192 delivered by a
      remote afterloading system through catheters introduced intraoperatively. The
      survivals ranged from 3 to 13 months. Due to the proximity of this portion of
      biliary duct to the hepatic hilus, invasion of the adjacent structures such as
      the portal vein and hepatic artery is common. Hence, complete resection is
      difficult and palliative surgical approach is usually adopted. Results of our
      treatment and review of relevant documents are presented.

PMID- 1396078
TI  - [Extracranial meningioma--a report of 6 cases].
AB  - Six cases of extracranial meningioma (EM) are reported. In addition to the
      routine paraffin section and HE stain as examined by light microscope, immuno
      histochemical studies with antibodies against vimentin, EMA, CK1, and S-100 were
      done. One specimen was examined by electron microscopy as well. For subdivision,
      4 belonged to meningotheliomatous type and each of the rest belonged to
      transitional and psammomatous types respectively. According to Lopez's
      classification, 5 were Type II and 1 was Type III. The significance of Lopez's
      classification of this tumor in clinical diagnosis and differential diagnosis, in
      histogenesis and pathogenesis are discussed.

PMID- 1396079
TI  - [Photodynamic therapy of nasopharyngeal carcinoma by argon or dye laser--an
      analysis of 137 cases].
AB  - 137 cases of nasopharyngeal carcinoma were treated by photodynamic therapy (PDT).
      Forty-eight and 72 hours after iv administration of 3-5 mg/kg HpD, laser
      treatment with either argon or dye laser was given. Dye laser (630 nm) with over
      350 mw output transmitted through quartz fiber was given to 57 patients. Argon
      laser (488 nm and 514.5 nm) was delivered to 80 patients. The results were:
      complete response 76 cases (55.47%) and marked response 47 cases (34.31%), with
      an over-all marked response rate of 89.78% (123/137). The efficacy and indication
      of photodynamic therapy for nasopharyngeal carcinoma using various light sources
      (argon and dye laser) are discussed.

PMID- 1396080
TI  - [Treatment of double primary lung cancers in 23 patients].
AB  - Twenty-three patients with double primary lung cancers (10 synchronous, 13
      metachronous) were diagnosed from 1967-1988 by operation, pathology or cytology.
      The incidence of double primary lung cancers was 1.5% (23/1527) among all lung
      cancers patients admitted during the same interval. Ten of these 23 patients
      (43.2%) received operative treatment. The synchronous double primaries were
      treated by limited resection. For the metachronous lesions, the first lung cancer
      was treated by the standard lobectomy and the second lesion by wedgectomy. The
      average survival time for the synchronous double lung cancers was 13 months which
      was similar to that of radiochemotherapy. For the metachronous cancers, the 5
      year survival of 5 operated patients was 40%. Only one of the other 8 patients as
      treated by non-operative means survived for more than 3 years. This shows the
      superiority of surgery to the non-operative treatment. Pathologic classification
      of the lesions in this series showed that 10 (43%) had identical types with the
      majority (6 patients) being of squamous-squamous cell type. In the 13 patients
      (57%) with different pathologic types 7 were of squamous-adenocarcinomas.
      Diagnostic criteria, operative method and vigilance to the possibility of double
      primary lung cancers are also discussed.

PMID- 1396081
TI  - [Diagnosis of breast cancer by computed infrared light scan].
AB  - One hundred and eleven patients with various pathologically proved breast
      diseases were examined by computed infrared light scan (ILS). The results were
      compared with those of palpation and X-ray mammography. The correct rate in 50
      cancers was 90%, significantly superior to that of X-ray (70%, P less than 0.05).
      The lower diagnostic rate of X-ray may have been due to higher percentage of
      younger patients (30-40 years of age) who had higher density in the breast in
      this group. The criteria of diagnosis of cancers by ILS on the video monitor
      were: 1. The shadow of the mass- the lower grade of gray-shade implied the
      possibility of malignancy, and 2. Pattern of the blood vessels around the mass
      increase in number, diameter, distortion, a zigzag course or disappearance of
      blood vasculature suggested malignancy. ILS is considered simple, non-invasive,
      easy to operate and reliable in the detection of breast cancers.

PMID- 1396082
TI  - [Surgical treatment of papillary thyroid carcinoma--report of 437 cases].
AB  - Four hundred and thirty-seven patients with papillary thyroid carcinoma were
      treated from April 1963 to December 1989. The main treatment was surgery which
      was divided into 4 types: lobectomy combined with neck dissection (RND or MND);
      total thyroidectomy; isthmusectomy plus lobectomy; lobectomy combined with RND
      and then followed by contralateral MND. The 10-year survival rates of these four
      groups were 88.6%, 89.5%, 80% and 80%, respectively. The over-all 5-, 10- and 15
      year survival rates were 92.7%, 87.9% and 79.4%. Lymph node metastasis was
      present in 80%. The authors believe that functional neck dissection is indicated
      if the number of lymph node is limited and the size is small.

PMID- 1396083
TI  - [Analysis of 26,826 patients with tumors in the head and neck].
AB  - A series of 26,826 patients with tumors in the head and neck as confirmed by
      pathology from January 1970 to December 1989 are analyzed. It accounted for 39.5%
      of all the tumors biopsied in the same interval. In this series, 72.41% was
      malignant which accounted for 45.77% of malignant tumors in the whole body. For
      benign tumors in the head and neck, the ratio of male to female was 0.84:1, and
      for malignant tumors in the head and neck it was 2.4:1. The most frequently
      involved site by the malignant tumors were: nasopharynx, mouth, maxillofacial
      regions and neck. The majority (62.65%) of malignant tumors were located in the
      nasopharynx which accounted for 28.68% of all malignancies, of which the ratio of
      male and female was 3:1, peak age was 41-50 years, 18 of them was under 10 years
      of age, the youngest was 1 1/2 years and the oldest was 84 years old. These data
      showed that malignant tumors in the head and neck regions, especially those in
      the nasopharynx, are common in Guangxi Province, China.

PMID- 1396084
TI  - [Diagnosis and treatment of primary retroperitoneal tumors].
AB  - New diagnostic imaging methods could shed much light on the diagnosis and
      treatment of retroperitoneal tumors. From 1978 to 1988, 98 patients were
      admitted. Eighty patients were treated by surgery and the diagnosis proved by
      pathology. In patients with primary malignant retroperitoneal tumors, 27 were
      completely resected and 18 received palliative resection. Of 18 benign tumors, 16
      were completely resected. In these 80 patients, biopsy was done in 17 patients.
      In patients with malignant tumors, a 5-year survival rate of 14% was obtained. In
      the resected benign tumors, a 5-year survival of 100% was obtained. Local
      recurrence was the chief cause of death.

PMID- 1396085
TI  - [A correlative analysis of T-lymphocyte subgroup and plasma selenium in patients
      with dilated cardiomyopathy].

PMID- 1396086
TI  - [Changes of atrial natriuretic peptide in dilated cardiomyopathy].

PMID- 1396087
TI  - [A 12-year clinical experience of cardiac valve replacement with domestic tilting
      disc valve prostheses in 1013 cases].
AB  - 1013 patients with cardiac valve replacement during a 12-year period from 1978 to
      1990 were reported. 566 cases were implanted with Shanghai-made tilting disc
      valve prostheses and 447 with Lanzhou-made (C-L valves). Mitral valve replacement
      (MVR) in 753 patients, aortic valve replacement (AVR) in 102 and double valves
      replacement (DVR) in 158. The overall early mortality rate was 6.2% with 4.9%,
      7.8% and 11.3% after MVR, AVR and DVR respectively. Follow-up study was made in
      3097.43 patient-year (mean 3.26 years). The late death rate was 1.6% patient
      years and with 1.4, 1.8 and 3.2 after MVR, AVR and DVR respectively. The
      incidence of late valve-related complication (% patient-years) were:
      thromboembolism 0.39, anticoagulant-related hemorrhages 0.77, prostheses failure
      0.22, prosthetic valve endocarditis 0.38, periprosthetic leak 0.12, and
      reoperations 0.38. The domestic tilting disc valve prostheses are considered to
      be qualified valves with low mortality and satisfactory results.

PMID- 1396088
TI  - [A clinical analysis of atrial-ventricular sequential pacing].
AB  - Forty one patients were implanted DDD pacemakers (3 cases DDDR) from August, 1983
      to July, 1990. 32 males and 9 females. The mean age was 62.3 years (range 32 to
      91). 19 patients had coronary artery disease. The indication for pacing was II
      degrees-III degrees AV block in 16 patients and sick sinus syndrome in 25
      patients. During follow-up period there were 2 patients had displacement, 4
      patients had undersensing, 3 patients had pacemaker-mediated tachycardia and 3
      patients had crosstalk. That was corrected through external programmer. The
      experience of this operation was discussed.

PMID- 1396089
TI  - [Relationship between different patterns of left ventricular hypertrophy and
      plasma norepinephrine and hemorheology in patients with essential hypertension].
AB  - The changes of plasma norepinephrine (NE) concentration and hemorheology in 60
      patients with essential hypertension (EH) with different patterns of left
      ventricular hypertrophy (LVH) were observed. The results showed that a higher
      value in whole blood viscosity (WBV) at a shear rate of 230-s was found in
      concentric hypertrophy (CH) group; a significant increase in plasma NE was found
      in asymmetric septal hypertrophy (ASH) group. It suggests that CH appear to be a
      compensation adapting to the increase in afterload. Significant increase in
      plasma NE concentration may play an important role in the development of ASH in
      addition to the afterload.

PMID- 1396090
TI  - [A study on spontaneous closure of ventricular septal defect using 2 dimensional
      echocardiography].
AB  - The results of 2 dimensional echocardiographic (2DE) observation in 73 patients
      with clinically diagnosed spontaneous closure of ventricular septal defect (VSD)
      were reported. 2DE showed that aneurysm of the membranous septum formed at the
      defect portion in 54 patients (74%), tricuspid valve leaflet tissue adhered to
      the defect portion in 2 patients, coarse appearance of the membranous septum in 8
      patients, no defect in 9 patients. There was no shunt flow detected in 59
      patients, trivial shunt flow in 14 patients on Doppler echocardiography. All VSD
      were of the membranous and perimembranous inlet type. The results of this study
      suggested spontaneous closure of membranous VSD was related to the aneurysmal
      formation of the membranous septum and adhesion of tricuspid valve tissue.

PMID- 1396091
TI  - [Validation of Doppler-derived interventricular pressure gradients in patients
      with ventricular septal defect comparing with catheterization study].
AB  - To evaluate the accuracy of Doppler echocardiography for measuring the
      interventricular pressure gradient in patients with ventricular septal defect
      (VSD), Doppler echocardiography and dual catheters were performed simultaneously
      in 31 cases with VSD ranging from 9 to 40 years old. The systolic jet velocities
      through VSD were recorded by the continuous-wave Doppler technique and converted
      to the peak instantaneous pressure gradient (delta Pp) and the mean pressure
      gradient (delta Pm) using a modified Bernoulli's equation with the aid of
      computer system. Both left and right heart catheters were performed to record the
      left (LVSP) and the right (RVSP) ventricular systolic pressure simultaneously.
      Guided by the color flow image Doppler technique, the tip of the right heart
      catheter was carefully placed within the jet area of the right ventricle. The
      following parameters were measured from the ventricular pressure curves, the peak
      instantaneous pressure gradient (IPG), the peak to peak pressure gradient (PPG)
      and the mean pressure gradient (MPG). The comparison between delta Pp and PPG
      yielded an excellent correlation (r = 0.99, SEE = 0.69 kPa). There was a close
      agreement between delta Pp and IPG (r = 0.99, SEE = 0.64 kPa). However, the
      correlation between delta Pm and MPG was also high (r = 0.98, SEE = 0.67 kPa). We
      conclude that Doppler echocardiography offers a reliable technique for measuring
      the interventricular pressure gradient in patients with VSD.

PMID- 1396092
TI  - [On viral myocarditis and dilated cardiomyopathy].

PMID- 1396093
TI  - [Surgical treatment of organic heart diseases with pre-excitation syndrome].

PMID- 1396094
TI  - [Balloon pulmonary valvuloplasty after initial pulmonary valvotomy for pulmonary
      atresia with intact ventricular septum].
AB  - Seven patients with pulmonary atresia and intact ventricular septum have
      undergone closed pulmonary valvotomy on the early neonatal period (2-6 days) with
      satisfactory results. Follow-up catheterization showed significant residual
      pulmonary valve stenosis requiring a second operation. Percutaneous balloon
      dilatation of the pulmonary valve was successful in 6 cases with the mean right
      ventricular systolic pressure reduced from 6.8 to 4.9 kPa (50.8 to 37 mmHg) and
      the mean transvalvular gradient dropped from 5.7 to 2.1 kPa (4.28 to 15.8 mmHg).
      One case failed and required surgical treatment. The results showed that balloon
      valvuloplasty could be applied instead of surgery for treatment of selected cases
      of pulmonary atresia with intact ventricular septum after an initial pulmonary
      valvotomy.

PMID- 1396096
TI  - [Pulsed Doppler study of left ventricular diastolic function and intervention by
      nifedipine in hypertension].

PMID- 1396095
TI  - [The relation between the serum peak value time and the marked effective time on
      electrophysiology after a stress dose of oral flecainide].

PMID- 1396097
TI  - [Protection on experimental sinus node dysfunction in rabbits with ginsenosides].
AB  - This experiment was carried out to evaluate the effect of ginsenosides from stems
      and leaves (GSL) on the sinus node dysfunction (SND) by observing the changes of
      the electrophysiological parameters of sinus node in limited period. Anesthetized
      rabbits were randomly divided into 3 groups. In the acute experiment, GSL, 50
      mg/kg, iv, was given to the GSL group (G), n = 12. Normal saline (NS), the same
      volume, to the control group (C), n = 12. After GSL was administered 30-50
      mg/kg.d for 14 days, iv, another data were obtained from chronic experimental
      group (CE), n = 15. The results show that the parameters, spontaneous cycle
      length (SCL), maximal sinus node recovery time (SNRTmax), corrected sinus node
      recovery time (CSNRT) were shorter in G group and CE group than C group
      respectively (P less than 0.05, P less than 0.01). It was suggested that GSL
      exerted protective effects on the experimental sinus node dysfunction.

PMID- 1396098
TI  - [Inhibition of experimental atherosclerosis in swine by nifedipine].

PMID- 1396099
TI  - [Accumulation of cholesterol esters in macrophages by normal very low density
      lipoprotein and its mechanism].

PMID- 1396100
TI  - [The relationship between the reperfusion-induced arrhythmias and the change in
      oxygen free radicals in myocardial venous blood].

PMID- 1396101
TI  - [Prognostic factors in idiopathic dilated cardiomyopathy].

PMID- 1396102
TI  - [The toxic effect of antimyocardial antibody on myocardial cell].

PMID- 1396103
TI  - Oral self-administration of pentobarbital by rhesus monkeys: relative reinforcing
      effects under concurrent signalled differential-reinforcement-of-low-rates
      schedules.
AB  - During daily 3-h sessions two separate pentobarbital solutions were concurrently
      available to rhesus monkeys under signalled differential-reinforcement-of-low
      rates (signalled DRL) schedules of mouth contacts with spouts. The schedules were
      synchronized so that each time the 30-s DRL interval expired, lights above both
      spouts were illuminated and a liquid delivery could be obtained either from the
      left or right spout, but not both. First water and then each of four 'comparison
      concentration' pentobarbital solutions (0.0625, 0.25, 1 and 4 mg/ml) were
      successively available under one schedule for a block of sessions. Concurrently,
      deliveries of a 'standard concentration' solution were available from the second
      spout under an identical DRL schedule; the concentration of this standard
      solution remained constant throughout the testing of the series of comparison
      solutions. Three pentobarbital concentrations (4, 1 and 0.25 mg/ml) in turn
      served as the standard concentration. Relative reinforcing effects were directly
      related to pentobarbital concentration: in general, within pairs of concurrently
      available pentobarbital solutions more behavior was maintained by the higher of
      the two drug concentrations. These findings are discussed in the context of
      previous studies using ratio and interval schedules which have found relative
      reinforcing effects to be directly related to reinforcer magnitude.

PMID- 1396104
TI  - Discriminative stimulus properties of cocaine, alone and in combination with
      buprenorphine, morphine and naltrexone.
AB  - Rats were trained to discriminate a dose of 10.0 mg/kg cocaine from saline.
      During substitution tests, both cocaine (5.6-10.0 mg/kg) and d-amphetamine (1.0
      3.0 mg/kg) produced greater than 80% responding on the cocaine-appropriate level.
      In contrast, buprenorphine (0.03-0.56 mg/kg), morphine (0.3-10.0 mg/kg) and
      naltrexone (1.0-10.0 mg/kg) failed to substitute for the cocaine stimulus, up to
      doses that substantially decreased rate of responding. When the cocaine dose
      effect curve was redetermined in the presence of selected doses of buprenorphine,
      the amount of cocaine-appropriate responding following a low dose of cocaine (1.0
      mg/kg) was increased slightly whereas cocaine-appropriate responding following
      higher doses of cocaine (3.0 and 5.6 mg/kg) was reduced slightly. Responding
      following the training dose of cocaine (10.0 mg/kg) was not changed. These
      results indicate that buprenorphine produced only small alterations in cocaine's
      discriminative stimulus effects and that the nature of these alterations differed
      depending on the dose of cocaine examined.

PMID- 1396105
TI  - The use of plasma levels to optimize methadone maintenance treatment.
AB  - The question of the optimal methadone dose during maintenance therapy is
      controversial. For both philosophical and practical reasons, therapeutic drug
      monitoring has not been generally used. Some therapists prescribe low doses of
      methadone more for psychological than pharmacological reasons. This study
      examines, in 104 methadone patients, the relation between self-rating, observer
      rating, urine tests, HIV-1 sero-status, daily methadone doses and plasma levels
      of methadone. No differences were found between HIV-1 infected and seronegative
      patients in these respects. The optimal methadone plasma level as judged by self-
      and observer-rating was more than 150 ng/ml. For oral methadone, the best results
      are obtained in patients receiving more than 90 mg daily. We found a significant
      relationship between methadone dose and plasma levels, also in patients who also
      used illicit drugs. We conclude that therapeutic drug monitoring should become
      routine in methadone treatment to achieve optimum results, especially in patients
      who complain of withdrawal symptoms and continue high-risk behaviour.

PMID- 1396106
TI  - Antisocial personality disorder, HIV risk behavior and retention in methadone
      maintenance therapy.
AB  - In a sample of 55 consecutive methadone maintenance admissions to our clinic, 42%
      were diagnosed with antisocial personality disorder (ASPD) using the National
      Institute of Mental Health Diagnostic Interview Schedule NIMH DIS. Individuals
      with ASPD exhibited greater risk for HIV infection as defined by more sexual
      contacts, needle use and equipment sharing. Data at 1 year follow-up were
      obtained on this group of patients. The objective was to compare the ASPD and non
      ASPD groups with regards to demographics, drug abuse history, outcome and
      retention in treatment. There were no significant differences between the groups
      on any demographic or treatment outcome variables. Survival analysis indicated
      that there were no group differences in treatment retention. In conclusion,
      although there were no differences in treatment outcome between ASPD and non-ASPD
      groups it is possible that ASPD patients who drop out of treatment will be at
      higher risk for contracting and spreading HIV within the IV drug using
      population. These data also suggest that in this population the diagnosis of ASPD
      using primarily behavioral traits as measured in the NIMH-DIS-III, has little
      utility in predicting treatment outcome.

PMID- 1396107
TI  - The image of self and of the environment in drug abusers: a comparative study
      using the TAT.
AB  - This study attempted to add to our understanding of the heroin abusers' identity
      problems, using images of the self and the environment. Murray's Thematic
      Apperception Test (TAT) was applied to a group of male drug users undergoing
      withdrawal treatment with methadone and also to a group of male, non-drug using
      controls. The needs of the subjects and the demands of the environment, plus
      interaction between the two, were compared between the two groups to obtain
      information about the self and lifestyle. Among the data which emerged, is an
      increased need for destructive aggression and an environment experienced as
      coercive and emarginating. Among the interactions we observed coerced
      imagination, difficulties in identification, personal relationships based on
      abandonment with persecutory projection of the female figure and a tendency
      toward immature defences such as avoidance, denial and acting out. This
      information is discussed in relation to possible means of treatment.

PMID- 1396108
TI  - Buprenorphine alone and in combination with naloxone in non-dependent humans.
AB  - This study evaluated the effects of concurrent naloxone on the opioid agonist
      effects of buprenorphine, a mixed agonist-antagonist marketed as an analgesic and
      under development as a treatment for drug abuse. In a residential laboratory
      seven non-physically-dependent opioid abuser volunteers received intramuscular
      buprenorphine (0.4 mg or 0.8 mg/70 kg) alone and in combination with naloxone
      (0.4 mg or 0.8 mg/70 kg) versus placebo. Buprenorphine produced dose-related
      opioid agonist effects on physiological and subjective measures. Concurrent
      naloxone attenuated the opioid agonist effects of buprenorphine. Thus, a
      combination product of buprenorphine and naloxone may have lower abuse liability
      than buprenorphine alone.

PMID- 1396109
TI  - Elementary schoolchildren's use of alcohol, cigarettes and marijuana and
      classmates' attribution of socialization.
AB  - In each of 2 years beginning in fourth and fifth grades, urban elementary public
      schoolchildren completed surveys about abusable substance use and health
      promoting behaviors and completed an instrument that permitted each child to have
      a socialization score attributed by classmates. A factor weighted 12-item scale
      was developed from 15 items in three domains (personal, interpersonal and
      school). The scale was positively correlated over the 2 years and positively
      correlated with a healthful activities scale in both years. Conditional multiple
      logistic regression, matching on school classroom, indicated that socialization
      was negatively associated with use of alcohol without parental permission and
      cigarettes in both years (grades 4-5, grades 5-6) and with use of marijuana in
      year 1. Socialization measured in year 1 was negatively associated with cigarette
      use in year 2 and with onset of use from year 1 to year 2. Shyness, a non
      socialization scale item, was negatively associated with use of cigarettes in
      both years and with use of alcohol without permission and use of marijuana in
      year 2. Being 'good at sports' was an attribute positively associated with
      alcohol use without permission and cigarette use in year 2. Results suggest that
      elementary schoolchildren can ascribe social characteristics to their classmates
      that are associated with and predict health related behaviors.

PMID- 1396111
TI  - Gonadotrophin releasing hormone analogues for advanced prostate cancer.

PMID- 1396110
TI  - Biochemical resistance to development of morphine-dependence in rats: biogenic
      amines, its receptors and antibodies.
AB  - The level of norepinephrine (NE), epinephrine (E) and dopamine (DA) in
      hypothalamus and blood plasma along with antibodies to NE, DA and serotonin (5
      HT) and characteristics of alpha 1-, alpha 2-adrenergic, D2-dopaminergic and S2
      serotoninergic receptors in synaptic brain membranes were studied in two groups
      of rats predisposed or resistant to the formation of physical morphine
      dependence. The resistant animals were characterized by a significant elevation
      of DA levels in blood plasma, elevation of antibodies to NE, and by higher
      concentration of alpha 2-adrenergic receptors in the brain cortex and of D2
      receptors in striatum. The affinity of D2-receptors to dopamine in resistant rats
      also was higher than in predisposed animals. The other parameters studied did not
      differ significantly between the two groups. These findings suggest that the
      increased activity of DA and NE neurotransmitter systems can be a cause for the
      genetic resistance of some individuals among Wistar rats to the formation of
      physical dependence on morphine.

PMID- 1396113
TI  - [Learning to live with long-term patients. A task for nursing education?].

PMID- 1396114
TI  - [Power--powerlessness--force].

PMID- 1396112
TI  - Managing the premenstrual syndrome.

PMID- 1396115
TI  - [Understanding by health personnel of their own role in a long-term facility for
      chronic psychiatric patients].

PMID- 1396116
TI  - [The work of nursing personnel in the area of psychiatric nursing].

PMID- 1396117
TI  - [Superannuated patients in extended care psychiatric facilities].

PMID- 1396118
TI  - [Social rehabilitation of patients from long-term psychiatric care facilities].

PMID- 1396119
TI  - [Dependence and psychosis as the foacal point of therapeutic activity. First
      experiences in a psychiatric county hospital].

PMID- 1396120
TI  - [A long-term care group for sexually abused children--on their way to return to
      childhood].

PMID- 1396121
TI  - [Limitations of Bruno Bettelheim's milieu therapy].

PMID- 1396122
TI  - [Abolition of psychotherapy. Jeffrey M. Masson's new book--a contribution to the
      destruction of myths in psychotherapy].

PMID- 1396123
TI  - [Pediatric nursing in the training of pediatric nursing. Recommendations for the
      training].

PMID- 1396124
TI  - [Working mothers and childrens wellbeing].

PMID- 1396125
TI  - [Decree on psychiatric personnel. Position of the Central Work Group within the
      German Association of Nurses].

PMID- 1396126
TI  - [Nursing science and nursing research. Necessity or luxury?].

PMID- 1396127
TI  - [Antineutrophil cytoplasmic antibodies in chronic inflammatory bowel diseases].
AB  - Serum samples from 83 patients (42 women, 41 men, mean age 41 [19-85] years) with
      chronic inflammatory bowel diseases (ulcerative colitis: n = 41, Crohn's disease:
      n = 42) of differing degrees of activity were tested for antineutrophil
      cytoplasmic antibodies (ANCA) by immunofluorescence microscopy and various ELISA
      techniques. Seven patients with ulcerative colitis and one with Crohn's disease
      were suffering from associated primary sclerosing cholangitis. ANCA were detected
      in 18 sera, 13 from patients with ulcerative colitis (31.7%) and five from
      patients with Crohn's disease (11.9%). Six of the eight patients with primary
      sclerosing cholangitis were ANCA-positive. Nine sera showed a cytoplasmic (c-ANCA
      ) pattern and 9 others showed a partially atypical perinuclear (p-ANCA-) pattern.
      Among the ANCA-positive sera, ELISA techniques showed that two had antibodies
      against serine proteinase 3, two against lactoferrin, two against elastase and
      one against myeloperoxidase. There was no correlation between the anatomical
      pattern or activity of the disease and the presence of ANCA. The antineutrophil
      cytoplasm antibodies demonstrable in chronic inflammatory bowel disease appear to
      be directed against so far unknown antigens. They are particularly frequent in
      patients with associated primary sclerosing cholangitis.

PMID- 1396128
TI  - [Intraoperative transesophageal echocardiography in large heart tumors].
AB  - A 46-year-old woman known to have an asymptomatic left atrial tumour suddenly
      developed dyspnoea, tachycardia (up to 140 beats/min) and a fall in systolic
      blood pressure to 80 mm Hg, 12 days after an extensive radical operation for
      metastatic ovarian carcinoma. Echocardiography demonstrated a large left atrial
      tumour which impaired left ventricular filling. A previously healthy 42-year-old
      man reported increasing exertional dyspnoea with retrosternal feeling of
      tightness. A 2/6 systolic murmur was audible over the cardiac apex, a 3/6
      diastolic murmur heard maximally over the 2nd intercostal space, and there was a
      third heart sound. The chest X-ray film demonstrated pulmonary venous congestion
      and there was an enlarged P-wave in the ECG suggesting left-atrial enlargement.
      Echocardiography revealed a myxoma-like tumour in the left atrium. A thoracotomy
      was performed in both patients. Using intra-operative transoesophageal
      echocardiography, the attachment of the tumour (in both instances a myxoma), the
      course of the operation and, after tumour removal, normal valvar and cardiac
      function were demonstrated. In case 2, the echocardiographic findings justified
      an atypical approach via the right atrium. In both patients removal of the tumour
      and the postoperative course were without complication.

PMID- 1396129
TI  - [The rectus abdominis syndrome].
AB  - Three athletes (one female, two males), aged 18-21 years, developed acute
      abdominal pain, two of them immediately after exercise including abdominal muscle
      training. The female patient had a pulmonary infection of uncertain cause at the
      time. The second patient obviously suffered from an allergic or parasitic disease
      (eosinophilia of 26%). The third patient, a swimmer, had the symptoms in the
      course of a flu-like infection after drinking about 100 g alcohol. Serum
      creatinine kinase activity was 7,800-17,500 U/l, making acute muscle damage
      likely, probably rhabdomyolysis. Ultrasound examination revealed echo-dense areas
      of the rectus abdominis muscle in two of the patients, in one of them associated
      with marked muscle swelling. In the third patient ultrasound was unremarkable
      during a symptom-free interval 8 days after the onset of symptoms. These
      observations indicate that even during banal infections sport exercise involving
      special strain on the abdominal musculature should not be undertaken because of
      the risk of rhabdomyolysis.

PMID- 1396130
TI  - [Pseudoxanthoma elasticum. Clinically typical but frequently overlooked].
AB  - A 52-year-old man had small yellowish, striated or reticular papules since the
      age of 5 years. These appeared first on the large flexures, and later on the
      neck, abdomen, penis and the mucosa of the lips. He developed angina at the age
      of 47 years. A bypass operation, however, did not lead to complete regression of
      cardiac symptoms. Four years later, the vision in his right eye deteriorated
      because of arterial occlusion, and the patient was treated with laser
      coagulation; he was started on long-term treatment with acetylsalicylic acid (250
      mg/d) and calcium dobesilate (1,500 mg/d). Despite this, the vision in his left
      eye also deteriorated progressively. Fundoscopy revealed bilateral pigmentary
      changes in the macular region, variations in the retinal arterial diameters and
      "angioid streaks". Pulses were absent in the right radial artery, the left
      posterior tibial artery and both dorsalis pedis arteries, but there were no
      trophic changes or symptoms. The serum total cholesterol (246 mg/dl),
      triglycerides (177 mg/dl) and LDL-cholesterol (193 mg/dl) were only slightly
      elevated. The diagnosis of pseudoxanthoma elasticum with typical changes in the
      elastic fibres was confirmed by elastin staining in a biopsy from one of the
      lesions.

PMID- 1396131
TI  - [The diagnosis of pleural effusions].

PMID- 1396132
TI  - [Chronic intestinal pseudo-obstruction].

PMID- 1396133
TI  - [A single dosage of gentamicin?].

PMID- 1396134
TI  - [The spontaneous course of Lyme arthritis in children].

PMID- 1396135
TI  - [The dawn or Somogyi phenomenon? High morning fasting blood sugar values in young
      type-1 diabetics].
AB  - High blood sugar levels in the morning in juvenile type 1 diabetics may be caused
      by a Somogyi phenomenon (counter-regulation after nocturnal hypoglycaemia) or
      insulin resistance in the morning hours (dawn phenomenon). To enable
      differentiation between the two, 1,562 blood sugar profiles (24 h, 3 h, 6 h) were
      determined in 161 children and juveniles (74 boys, 87 girls; mean age 10.8 [1.0
      19.7] years) with type 1 diabetes mellitus. In accordance with the mechanism of
      the dawn phenomenon there was a close positive correlation between the blood
      sugar levels in the night and morning (r = +0.696; P less than 0.0001); the mean
      fasting blood sugar level was about 60 mg/dl above the 3 h value. Low nocturnal
      blood sugar levels as a possible cause of a high morning blood sugar (greater
      than 250 mg/dl) was demonstrated in fewer than 1% of profiles. On the other hand,
      the probability of nocturnal hypoglycaemia rose exponentially in the presence of
      low morning fasting blood sugar levels. Thus, if the morning level was below 80
      mg/dl, the blood sugar levels at 3 h was below 50 mg/dl in 41.2%. This indicates
      that high morning blood sugar levels result from the dawn phenomenon and require
      a higher evening dose of slow-release insulin. But if the morning blood sugar
      values are clearly below 100 mg/dl, the cause may be nocturnal low blood sugar
      levels and the evening insulin dose should, therefore, be reduced.

PMID- 1396137
TI  - [Lemierre's syndrome with splenic abscesses].
AB  - A week after onset of a pharyngo-tonsillitis a previously healthy 23-year-old man
      developed high fever (41.4 degrees C), leukocytosis (12,200/microliters) with
      marked shift to the left, thrombocytopenia (86,000/microliters) and increased
      transaminases (GOT 83 U/l, GPT 113 U/l). Chest x-ray film suggested
      intrapulmonary abscesses with left-sided pleural effusion. The suspected
      diagnosis of "post-tonsillitis" septicaemia (Lemierre's syndrome) was confirmed
      by demonstrating anaerobic, fusiform, gram-negative bacteria (Fusobacterium
      nucleatum and necrophorum) in several blood cultures. Despite antibacterial
      treatment (amoxicillin/clavulanic acid, imipenem/cilastatin, clindamycin) he had
      recurrent pain referred to the kidney region and persisting fever. Repeated
      ultrasound and radiological examinations revealed new foci in the spleen, which
      were enlarging. Laparotomy with splenectomy performed on day 17 after the begin
      of treatment confirmed multiple splenic abscesses, but abscess pus and splenic
      tissue were sterile. After altogether 6 weeks of antibiotic treatment, finally
      with chloramphenicol, the patient was discharged in a good general state.

PMID- 1396136
TI  - [Goiter epidemiology in South Tirol].
AB  - To ascertain the prevalence of goitre among schoolchildren in South Tyrol
      (uncontrolled voluntary iodine salt prophylaxis), the size of the thyroid gland
      was determined by palpation and ultrasound in 1,013 of 1,224 children, aged 6 to
      14 years (547 boys, 466 girls), selected by statistically criteria. At the same
      time, to assess thyroid function, total and free fractions of T3 and T4, and TSH
      were measured, while iodine supply was determined by measuring urinary iodine.
      Stage Ia goitre was diagnosed by palpation in 157 children, stage Ib in 18 and
      stage II in two (goitre prevalence of 1.97% according to WHO criteria). Mean
      thyroid volume as determined by ultrasound was 4.26 (0.8-23.4) ml. As expected,
      it increased with age and body surface area: it was 2.55 +/- 0.49 ml in 6-year
      olds, 3.83 +/- 0.42 ml in 10-year olds and 6.42 +/- 0.69 ml in 14-year olds.
      Iodine excretion (143.8 [4.1-984.8] micrograms iodine/g creatinine) indicated
      adequate iodine supply to the tested subjects. South Tyrol is thus, according to
      WHO criteria, no longer an endemic goitre area. The voluntary use of iodinated
      cooking salt and changed food habits have probably effected this change in goitre
      epidemiology.

PMID- 1396138
TI  - [Cardiac involvement in the hypereosinophilia syndrome. the importance of
      echocardiography in the follow-up].
AB  - A 51-year-old man and a 39-year-old woman with the hypereosinophilic syndrome
      developed a restrictive cardiomyopathy in the course of cardiac involvement.
      Echocardiography demonstrated typical thrombotic obliteration at the apex of both
      ventricles. Doppler ultrasound showed changes of impaired filling in both
      ventricles. Glucocorticoid treatment (prednisone, 85 mg daily) had to be
      drastically reduced (to 10 mg daily) in case 1, because of the development of a
      Cushing syndrome. The man died 18 months later of advanced heart failure. In the
      woman the eosinophil count fell after prednisone administration (1 mg/kg daily)
      and there was no recurrence. But heart failure due to impaired diastolic filling
      has persisted so that orthotopic cardiac transplantation has been planned.

PMID- 1396139
TI  - [The therapy of pleural effusions].

PMID- 1396141
TI  - [The indications for surgery in abdominal aortic aneurysm].

PMID- 1396140
TI  - [The therapeutic possibilities in Gilbert's disease].

PMID- 1396142
TI  - [Extensive gastric mucosal necrosis after endoscopic injection therapy].

PMID- 1396143
TI  - [The antiphospholipid syndrome following tattooing?].

PMID- 1396145
TI  - [Recanalization of occluded coronary arteries using the Magnum system].
AB  - Recanalization procedures with the "Magnum" system were undertaken in 137
      patients (113 men, 24 women; mean age 57.1 +/- 8.1 years) with complete occlusion
      of a coronary artery. The system consists of a 0.021 inch guidewire with a
      flexible 1 mm diameter olive tip, a double-lumen probing catheter and a Magnarail
      balloon catheter. Chronic coronary artery occlusion of maximally 3 months was
      present in 51 patients (37%), for over 3 months in 52 (38%), while the duration
      of occlusion was unknown in 18 (13%). An acute coronary occlusion was
      successfully recanalized in 7 patients (5%), while in 9 (7%) it was accomplished
      when it had occurred during or shortly after a percutaneous coronary artery
      angioplasty (PCTA). The occlusion was successfully passed in 87 patients (64%);
      in 15 of them recanalization with another system had failed. The highest success
      rates were obtained with an acute occlusion (5 of 7; 71%), occlusion of 3 months'
      duration or less (39 of 51; 76%), and occlusion during PTCA (8 of 9; 89%). The
      success rates were lower for occlusions over 3 months' duration (25 of 52; 48%; P
      < 0.05) and of unknown duration (10 of 18; 56%; n.s.). Recanalization after
      failed recanalization was successfully accomplished by rotation-angioplasty (n =
      2) or a standard system (n = 4).--These results indicate that the Magnum system
      is suitable for recanalizing chronic or acute coronary occlusion. But
      cardiologists should be capable of using several systems to increase the chances
      of successful recanalization.

PMID- 1396144
TI  - [The radiological diagnosis of maxillary sinus aspergillosis].

PMID- 1396146
TI  - [Lactose intolerance in chronic inflammatory bowel diseases].
AB  - In 124 patients with Crohn's disease (69 women, 55 men; mean age 33.7 [11-66]
      years) and 53 with ulcerative colitis (30 women, 23 men; mean age 36.2 [19-74]
      years) the incidence of lactose intolerance, as measured by the H2 breath test
      and blood sugar concentration, was determined prospectively. To exclude abnormal
      bacterial colonization of the small intestine or rapid small-intestine transit
      after partial resection of the small intestine as a cause of lactose intolerance,
      the oro-caecal transit time for lactulose (H2 breath test) was measured. While 21
      of 124 patients with Crohn's disease (16.9%) had the expected incidence of
      lactose intolerance, this was present in only 2 of 53 patients with ulcerative
      colitis (3.8%; P < 0.05). The lactose intolerance was independent of the site of
      any inflammatory changes, disease activity and extent of small-intestine
      resection. Oro-caecal transit time for lactose was similar for all patients.
      There was no lactose intolerance in two patients with abnormal small-intestinal
      bacterial colonization.--Because of their considerable diagnostic and prognostic
      significance, tests for lactose intolerance should be performed routinely in all
      cases of Crohn's disease or ulcerative colitis.

PMID- 1396147
TI  - [Gustatory sweating demonstrated by infrared thermography].
AB  - A 35-year-old man, previously healthy except for a grade 1 goitre, sustained a
      spontaneous left pneumothorax treated with a Bulau drain. When the left
      pneumothorax recurred 2 months later a left thoracotomy was performed. Two bullae
      at the lung apex were resected and a pleurodesis performed. After the operation
      the patient noted hypaesthesia of the dorsum of the left upper arm, mild ptosis
      of the left eyelid as well as reduced sweat secretion over the left half of the
      face and the left rib cage. The hypaesthesia improved, but the sympathetic nerve
      deficits remained. There were no other neurological signs. 9 months later, within
      one minute of eating a sour apple, the patient developed severe sweating over the
      left half of the face and the left chest. The reaction was confirmed by infra-red
      thermography which proved that the skin temperature in the sweating region had
      fallen to 3 degrees C. The likely cause of localized gustatory sweating is intra
      operative damage of the stellate ganglion or its preganglionic nerve connections.
      Treatment is limited to avoidance of the precipitating gustatory stimulus.

PMID- 1396148
TI  - [Diagnosis of bradycardic arrhythmia].

PMID- 1396149
TI  - [Mental health and social situation in old age].

PMID- 1396150
TI  - [Serodiagnosis of autoimmune diseases].

PMID- 1396151
TI  - [External radiotherapy in differentiated thyroid carcinoma].

PMID- 1396153
TI  - [Neopterin and blood transfusion].

PMID- 1396152
TI  - [Thrombolysis of right atrial transit thrombus].

PMID- 1396154
TI  - [Consumption coagulopathy in meningococcal infection].

PMID- 1396155
TI  - [Stress echocardiography as a routine examination in coronary heart disease].
AB  - The value of stress echocardiography in the routine diagnosis of coronary heart
      disease was assessed in 100 consecutive patients (22 women, 78 men; mean age 57
      [32-83] years) scheduled for coronary angiography because of suspected angina.
      Exercise consisted of bicycle ergometry (n = 50), on the one hand, simulated
      exercise with transoesophageal atrial stimulation (n = 16), dipyridamole (n = 33)
      and dobutamine (n = 33) infusions, on the other. 91 patients were successfully
      tested by at least one of these procedures, while exercise electrocardiography
      was successfully employed in only 78 (P < 0.05). Stress echocardiography had a
      greater sensitivity than exercise electrocardiography (90% vs 78%) and
      specificity (90% vs 73%). Semiquantitative measurement of wall movement
      distinguished patients without functionally effective stenosis from those with
      single or multiple vessel disease (P < 0.001). Stress echocardiography thus makes
      it possible in most cases to demonstrate or exclude functionally significant
      coronary artery stenoses.

PMID- 1396156
TI  - [The analysis of a severe side effect of a cartilage-protective agent by
      immunological studies].
AB  - After 18 intramuscular injections of Arumalon, a 62-year-old woman with
      degenerative hip-joint changes developed a severe illness with fever up to 39
      degrees C, swellings of the finger, hand and knee joints, as well as a local skin
      rash and changes in the blood (WBC 1900/microliters, platelets
      113,000/microliters), and increase in liver enzymes (GOT 83 U/l, GPT 93 U/l,
      lactate dehydrogenase 693 U/l). Arumalon, a glucosaminoglycan-peptide complex
      containing a watery extract of bovine cartilage and bone marrow, is used as a
      cartilage-protecting medication. The close temporal relationship between the
      injections and the symptoms suggested that the illness was drug-induced. This
      view was supported by a positive lymphocyte transformation test with Arumalon and
      its constituents, as well as by the demonstration of Arumalon-specific antibodies
      in the cultured lymphocyte fluid while the serum was negative for the antibodies.
      The illness took a protracted course. The patient became completely free of
      symptoms only after a year on a maintenance dose of prednisone, 15 mg daily. As a
      local inflammatory reaction was noted at the very start of the Arumalon
      injections, presensitization against the foreign proteins in Arumalon cannot be
      excluded. This is also supported by the fact that the specific lymphocyte
      proliferation was essentially unchanged even after nine months. This case
      illustrates the importance of careful assessment of increased and repeated
      manifestations of local reaction during Arumalon treatment, in particular in view
      of the risk of systemic side effects.

PMID- 1396157
TI  - [The accidental aspiration and ingestion of petroleum in a "fire eater"].
AB  - A 26-year-old man, practicing for a variety performance as "fire-eater",
      accidentally inhaled and ingested about 10 ml petroleum. Soon afterwards he
      developed dyspnoea, an urge to cough, fever up to 39 degrees C and loss of
      retentiveness. He was treated as an out-patient with doxycycline, 100 mg daily,
      and aspirin, 500 mg three times daily. While this reduced the dyspnoea, the
      elevated temperature persisted and he had haemoptysis. Chest x-ray and computed
      tomography 12 days after the aspiration revealed areas of atelectasis and of
      liquefaction necroses. Bronchoscopic and cytological examinations showed
      eosinophilic alveolitis and mucosal necrosis in both main bronchi. The symptoms
      were improved by two inhalations of beclomethasone four times daily, and systemic
      treatment with prednisolone, 50 mg daily, together with parenteral antibiotic
      administration (cefotaxime, 1.0 g twice daily). The focal lung lesions regressed
      completely within a few weeks. Five months after the aspiration computed
      tomography merely demonstrated discrete scarring of the previously necrotic
      lesions. This case illustrates that, even with extensive necrotic lung changes
      after petroleum aspiration, conservative treatment is justified and likely to be
      effective.

PMID- 1396158
TI  - [The therapy of bradycardiac arrhythmias].

PMID- 1396159
TI  - [The timing of the patient being informed. The judgement of the Federal Supreme
      Court of 7 April 1992].

PMID- 1396161
TI  - [The sensible choice of diagnostic measures].

PMID- 1396160
TI  - [Breast carcinoma and later hormonal osteoporosis prevention].

PMID- 1396162
TI  - [The Shy-Drager syndrome].

PMID- 1396163
TI  - [Abortions caused by protozoa in agricultural animals].
AB  - A review is given on abortions in livestock caused by Toxoplasma gondii, Neospora
      caninum and Sarcocystis spp. Special emphasis is put on diagnostic procedures. T.
      gondii is considered to be a major cause of abortions in sheep and goats.
      Diagnosis is based on the characteristic lesions in the cotyledons, histologic
      and immunohistochemical examination, and on the detection of specific antibodies
      in body fluids or serum of aborted fetuses. Whether abortions in swine due to T.
      gondii are of practical importance is still unclear. The most important causative
      protozoal agent of abortions in cattle is Neospora caninum. This protozoon was
      found in 19 per cent of cattle fetuses submitted for examination in USA.
      Occasionally it was found also in aborted lambs, kids and foals. Diagnosis is
      based on the histologic or immunohistochemical detection of the parasite.
      Abortions can be regularly induced experimentally in large and small ruminants
      and in pigs by the oral inoculation of sporocysts of certain Sarcocystis species.
      However, under natural conditions abortion due to Sarcocystis was diagnosed only
      occasionally and only in cattle and sheep. The histologic examination of the
      fetus and fetal membranes is the only way to diagnose Sarcocystis abortion or
      neonatal infection at present.

PMID- 1396165
TI  - [Use of anthelmintics for nematode control in sheep in West Germany: results of a
      survey].
AB  - A survey by questionnaires was performed on 543 (0.9% of all) sheep flocks in
      western Germany in 1988/89 to obtain informations about deworming practices
      against gastrointestinal nematodes. The major informations are: Anthelmintic
      treatments were associated with the reproductive status of ewes and the breeding
      of lambs in most of the flocks. They were performed at an epidemiologically
      appropriate time in many cases but were not accompanied by essential management
      practices. (Pro)benzimidazole compounds were the anthelmintics most frequently
      used by more than 95% of the farmers; 22% and 13% of the farmers additionally or
      exclusively administered levamisole/pyrantel and ivermectin, respectively. On
      average, treatment of ewes and lambs against nematodes was performed 2.5 times
      and 2.8 times a year, respectively. The mean frequency of deworming differed
      regionally and was generally greater in pedigree breeding flocks than in
      commercial breeding flocks; it was significantly affected by the husbandry
      system, the number of ewes per flock, the size of available pasture and the class
      of anthelmintics employed. The results of this survey revealed that many German
      sheep farmers obviously lack an awareness of the rationale of preventive and
      economic control practices against gastrointestinal nematodes.

PMID- 1396164
TI  - [The helminth fauna of red foxes (Vulpes vulpes Linnaeus 1758) in north Hesse and
      east Westphalia. 1. Cestodes].
AB  - Between November 1989 and June 1990 a total number of 397 foxes were examined for
      the presence of cestodes. The animals came from the districts of Arnsberg,
      Detmold and Kassel. In 16.4% of the foxes infections with Echinococcus
      multilocularis were found, in 28.5% Taenia crassiceps, in 14.4% Taenia
      polyacantha, in 4.3% Mesocestoides spp., in 3.3% Multiceps multiceps, in 2.5%
      Hydatigera taeniaeformis, in 0.8% Taenia hydatigena and in 0.3% Taenia martis.
      Infections with Echinococcus multilocularis very often showed high worm numbers
      of more than 1000 per fox. The number of worms for the other cestodes mostly
      varied between one and ten specimen per animal.

PMID- 1396166
TI  - [Calcinogenic plants and the incubation effect of rumen fluid].
AB  - This paper describes incubation effects of rumen fluid on aqueous extracts of
      Trisetum flavescens, Solanum malacoxylon, Nierembergia veitchii, and Cestrum
      laevigatum. Investigation was performed by the rachitic chicken test, parameters
      determined were the serum levels of Ca, P, and alkaline phosphatase. Extracts of
      S. malacoxylon, and C. diurnum as well as 1,25(OH)2-VitD3-25-O-glucoside gave
      (without incubation) an increased activity, while with incubation a small
      additional effects could be observed. The extracts of T. flavescens and N.
      veitchii did not show any alteration with or without incubation. Comparable
      effects were obtained with 1,25(OH)2VitD3-1-O-glucoside, as well as
      1,25(OH)2VitD3-3-O-glucoside.

PMID- 1396167
TI  - [Viral agents as the cause of reproductive disorders in cattle and available
      vaccines].
AB  - After a review on the viral agents playing a role in diseases of cattle those
      related to the occurrence in the genital tract are described. They may be causing
      abortion or local reactions leading to a reduced fertility and/or be of
      importance for the embryo transfer. Bovine herpesvirus type 1 (BHV1) and the
      bovine virus diarrhoea virus (BVDV) are the agents most widely distributed in
      Europe. Both are of economic importance, described in detail and vaccines
      available discussed.

PMID- 1396168
TI  - Studies concerning etiology of sheep-associated malignant catarrhal fever in
      Europe.
AB  - The etiological agent of sheep-associated malignant catarrhal fever (MCF) in
      Europe has not been isolated directly from sheep. The occurrence of antibodies
      against the African bovine herpesvirus (BHV-3, WC 11) in cattle and sheep was
      examined using recently modified indirect immunofluorescence test (IIFT) and
      neutralization test (NT) methods. Studies revealed that sheep and cattle sera in
      Europe were free from neutralizing antibodies of BHV-3. The IIFT could not
      establish the presence of antibodies to African BHV-3 in cattle but revealed that
      about 22.4% of sheep sera reacted to it. Apart from the well known ovine
      herpesvirus (BHV-5), occurrence of another herpesvirus in Europe had been
      expected. This virus is not identical with the WC 11 strain, but it is in
      antigenic relationship to it. We had for the first time substantial serological
      evidence to the effect that sheep-associated MCF in Europe is a herpesvirus
      related to the African strain.

PMID- 1396169
TI  - [The relationship between bovine clinical mastitis at the time of parturition and
      retained placenta].
AB  - 868 parturitions were examined to determine the relation between the clinical
      mastitis around partition and the loosening process of the placenta in the
      bovine. The occurrence of mastitis in heifers and cows around parturition was
      18.7%. The frequency of retained placenta in animals with mastitis was
      significantly higher (p less than 0.01) than that in animals without mastitis
      influenced the loosening process of the afterbirth. The results support an
      hypothesis, that mastitis and retentio secundinarum can regard as signs of the
      decrease in the activity of the immune system.

PMID- 1396170
TI  - Oligodendrocytes from jimpy and normal mature tissue can be 'activated' when
      transplanted in a newborn environment.
AB  - Fragments of corpus callosum from P13 normal and jimpy (jp) mutant mice
      (containing only postmigrating precursors and differentiated oligodendrocytes
      (ODCs, some of them myelinating soon) have been transplanted into the thalamus of
      newborn shiverer (shi) mutant mice. The behaviour of transplanted ODCs has been
      assayed by immunohistochemistry of their myelin basic protein (MBP)-positive
      myelin synthesized in the host shi brain whose myelin is deprived of this
      component. ODCs and postmigrating precursors contained in P13 normal corpus
      callosum survived, migrated out of the graft and myelinated in the shi host
      parenchyma. The high ratio of positive cases observed was comparable to the one
      observed in previous experiments using fragments of newborn or embryonic normal
      tissue. When fragments of jp tissue were used as donors, postmigrating jp ODCs or
      precursors migrated on long distances out of the graft and synthesized large
      amounts of myelin as estimated by the size of the MBP-positive myelin patches
      present in the host shi brain. The extent of migration and the size of these
      myelin patches were more important than those observed in previous experiments
      using fragments of newborn or embryonic jp CNS as donors. By contrast, the low
      ratio of positive cases observed suggested that the survival of P13 jp ODCs or
      their postmigrating precursors cannot be restored by the newborn shi
      environment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396172
TI  - Co-transplantation of fetal or adult dorsal root ganglia and of autologous
      peripheral nerve segments to the adult rat spinal cord: extensive reinnervation
      of the grafted nerves by the transplanted DRG cells.
AB  - Intraspinal transplantation of embryonic neurons and of autologous peripheral
      nerve segments is an essential tool for studying plasticity and repair in the
      adult mammalian spinal cord. Unlike adult central nervous system neurons, adult
      dorsal root ganglion (DRG) cells can be cultured in vitro and are assumed to
      survive transplantation. In the present work, we have co-transplanted adult (and
      also fetal, for comparison) DRG and peripheral nerve autografts to the cervical
      spinal cord of the adult rat. Similar results were obtained from both series:
      fetal as well as adult DRG cells did survive transplantation and nearly half of
      them grew lengthy axons into the grafted nerves. A few of them were seen to
      express a calcitonin gene-related peptide. Possibilities of central afferentation
      as well as of peripheral connectivity of these transplanted neurons is under
      study.

PMID- 1396171
TI  - Functional capacities of transplanted cell-sorted adult oligodendrocytes.
AB  - Previous work has shown that transplanted dissociated glial cells derived from
      neonatal rats can myelinate areas of the myelin deficient (md) rat spinal cord.
      In the present studies we have examined the ability of adult glial cells, either
      as suspension of mixed glial cells or as 01 positive oligodendrocytes purified by
      cell sorting, to myelinate md rat axons following transplantation. Mixed glial
      cell preparations from adult rats myelinated large areas of either, dorsal,
      lateral or ventral columns. These areas contained clumped, transplanted
      oligodendrocytes. In addition, preparations containing over 90% 01 positive
      oligodendrocytes were also capable of myelinating large numbers of axons upon
      transplantation. These results suggest that adult oligodendrocytes may play an
      important role in remyelination of the adult CNS.

PMID- 1396173
TI  - Maturation and fine structure of thalamic reticular neurons transplanted into the
      adult rat CNS.
AB  - This work was undertaken to determine whether or not cell suspension transplants
      provide a promising vehicle for the in vivo study of neuronal development. Cell
      suspensions of rat fetal tissue that contained both reticular (RT) and
      ventrobasal primordia were transplanted into the excitotoxically lesioned
      somatosensory thalamus of adult rats. The fine structure of transplanted
      GABAergic RT neurons that were identified by immunocytochemistry was investigated
      5 days to 7 months following transplantation. The dissociation and
      transplantation of the tissue results in disruption of the extracellular matrix
      and alteration of cellular interactions which could introduce major changes in
      neuronal maturation. Our results show that maturation of transplanted GABAergic
      RT neurons was comparable to normal and that they were able to establish and
      receive, with one exception, usual sets of connections. In contrast, disruption
      of the tissue was responsible for the definitive loss of organotypic
      characteristics and the emergence of abnormal connections, especially synaptic
      connections from somatosensory afferents, the functional significance of which
      will be important to determine.

PMID- 1396174
TI  - Xenogenic transplantation into newborn rodent brain: neovascularization of the
      graft by the host.
AB  - Neoangiogenesis of transplants implanted into the brains of newborn rodent hosts
      was evaluated by immunohistochemistry for 2 weeks after the operation. The use of
      species-specific antibodies directed against mouse endothelial cells demonstrated
      the respective participation of the host and the donor in the formation of new
      vessels in the graft after crossed rabbit into mouse and mouse into rat
      transplantation experiments. We show that blood vessels made by host endothelial
      cells begin to penetrate the transplant 24 h after grafting, and cross it
      completely by 72 h. Simultaneously, host astrocytes invade the transplant.

PMID- 1396175
TI  - New insight on the factors orienting the axonal outgrowth of grafted Purkinje
      cells in the pcd cerebellum.
AB  - Despite Purkinje cell replacement, leading to the repair of the cortical circuit
      of the pcd mouse cerebellum grafted with E12 cerebellar primordium, the
      reestablishment of the corticonuclear projection only occurs for some Purkinje
      cells and in a small percentage of grafted mice. In order to assess the
      importance of: (1) competition between host and grafted deep nuclei, and (2) the
      distance between the implants and the host deep nuclei, new grafted experiments
      have been performed. In the latter, solid grafts were taken from E13 or E14 donor
      embryos after removal of the region containing the postmitotic deep nuclear
      neurons, and randomly positioned at various cerebellar depths. With cortical
      implants, the absence of donor nuclear neurons is not sufficient to allow the
      axons of the grafted Purkinje cells that have invaded the host molecular layer to
      escape the confinement of this layer. The molecular/granular layer interface
      appears as an almost impassable obstacle, and the granule cell layer as a
      nonpermissive milieu. With grafts located between the host deep nuclei and the
      4th ventricle (deep grafts), the grafted Purkinje cells project massively to the
      host nuclei, but they are unable to leave the implant and, therefore, they are
      not integrated in the deficient cortical circuit. Finally, when the grafts
      positioned in the central white matter (intermediate grafts) disrupt the
      integrity of the host granule cell layer, some of the grafted Purkinje cells
      invade the host molecular layer, while most of them remain within the implant.
      Some axons of the cortically integrated Purkinje cells, using the nearby graft as
      a bridge, seem able to innervate the host deep nuclei. The latter, in addition,
      receive a massive projection from the nonintegrated Purkinje cells. These results
      emphasize the ability of grafted Purkinje cells to specifically innervate their
      target host neurons, when either there is proximity, or when a permissive
      microenvironment for their axonal outgrowth is created by embryonic grafted
      cortical cerebellar neurons, filling the gap between the molecular layer and the
      deep nuclei of the host.

PMID- 1396176
TI  - Raphe grafts in the hippocampus, but not in the entorhinal cortex, reverse
      hippocampal hyperexcitability of serotonin-depleted rats and restore their
      responsiveness to fenfluramine.
AB  - We compared the effects of embryonic raphe grafted into either the hippocampus or
      the entorhinal cortex, on the responsiveness of dentate granule cells to
      stimulation of the perforant path. Raphe grafts in the hippocampus reversed the
      hyperexcitability of granule cells, resulting from depletion of the serotonergic
      innervation. Such grafts also restored the responsiveness of the granule cells to
      application of a serotonin releasing drug, fenfluramine (FFA). In contrast,
      hyperexcitability was not reversed when the graft was placed in the entorhinal
      cortex. Furthermore, although some increase in population spike size was observed
      in these rats after application of FFA, this increase had a response profile
      which was different from that of control and of lesioned rats that were grafted
      in the hippocampus. These results suggest that the serotonergic innervation,
      within the hippocampus and not in the entorhinal cortex, modulates granule cells
      excitability.

PMID- 1396177
TI  - The fate of Schwann cells transplanted in the brain during development.
AB  - Purified rat Schwann cells labeled with Hoechst 33342 fluorescent fluorochrome
      were transplanted into the brain of the newborn shiverer mouse. The grafted cells
      survived and were able to migrate through the host parenchyma. However, Schwann
      cell migration was restricted to the grafted hemisphere and to structures
      adjacent to the graft. With time, Hoechst labeled cells, present at the site of
      implantation or dispersed in the host parenchyma, decreased progressively in
      number. Instead, they concentrated along the blood vessels, meninges and
      ventricles. Despite the presence of Hoechst labeled Schwann cells in white matter
      tracks during the process of central myelination, Schwann cell myelination could
      not be evidenced by immunodetection of the peripheral myelin protein or by
      ultrastructural observation of the typical Schwann cell basement membrane
      surrounding peripheral myelin. A series of additional transplantations involving
      Schwann cells of mouse or rat origin, grafted either as cell suspensions or as
      nerve fragments, demonstrated that transplanted Schwann cells formed myelin
      around developing host axons only when included in a nerve fragment.
      Immunodetection of GFAP in astrocytes and type IV collagen in basement membranes
      as well as electron microscopy showed that reactive astrocytes invaded the
      grafted area after the first week of transplantation and sometimes formed
      basement membranes isolating partially the graft from the host parenchyma. During
      host myelination, astrocytes, which were present in most white matter structures,
      surrounded grafted cells. Occasionally, they enclosed Schwann cells in basement
      membranes or encircled host axons. Later, reactive astrocytes were associated
      with Schwann cells restricted to blood vessel and ventricular walls, and
      meninges. Our results suggest that in the presence of competitive developing
      oligodendrocytes, astrocytes are able to limit migration and prevent myelination
      of Schwann cells transplanted in the newborn shiverer brain. In addition,
      astrocytes seem to be able to expel the grafted cells and finally exclude them
      from the host parenchyma.

PMID- 1396178
TI  - Type 1 astrocytes fail to inhibit Schwann cell remyelination of CNS axons in the
      absence of cells of the O-2A lineage.
AB  - The extent to which Schwann cells are able to remyelinate demyelinated CNS axons
      is influenced by the presence of astrocytes. In order to study further the nature
      of astrocyte control of Schwann cell remyelination in the CNS, cultures
      containing type 1 astrocytes and a small proportion of Schwann cells, but
      depleted of O-2A lineage cells by exposure to cytosine arabinoside and complement
      mediated immunocytolysis, were transplanted into glial-free lesions in adult rat
      spinal cord in which the host response to demyelinated axons was suppressed by X
      irradiation. Following transplantation of these O-2A lineage-depleted cultures
      into X-irradiated, demyelinating lesions, there was extensive remyelination of
      demyelinated axons by Schwann cells, a result which contrasted with those
      obtained from earlier experiments in which O-2A lineage cells were present within
      the transplant, and/or recruited from host tissue. This experiment shows that the
      presence of O-2A lineage cells is required in order for transplanted type 1
      astrocytes to organise in a manner which inhibits extensive Schwann cell
      remyelination of CNS axons.

PMID- 1396180
TI  - Pulse oximetry monitoring in patients with nasal packing.
AB  - Pulse oximetry is a safe, effective method of monitoring for hypoxia in patients
      with nasal packing. It provides continuous in vivo measurements of the patients'
      arterial oxygenation in a non-invasive fashion based on the principles of the
      hemoglobin dissociation curve.

PMID- 1396181
TI  - The justifications and controversies of panendoscopy--a review.
AB  - The triple endoscopies of direct laryngoscopy, bronchoscopy, and esophagoscopy,
      commonly known as panendoscopy, are frequent surgical procedures in
      otorhinolaryngology. Their purpose is to diagnose additional primary
      malignancies. The incidence of multiple synchronous primary malignancies has been
      reported between 3% and 13%. This unusually high rate is attributed to the
      process of field cancerization in which an anatomical region is exposed to a
      surface carcinogen and multifocal areas undergo irreversible change to multifocal
      malignancies. The majority of additional malignancies are diagnosed within 2
      years of the index tumor's diagnosis, and are most consistently diagnosed within
      routine panendoscopy. Nevertheless, a significant percentage (40%) of additional
      primary malignancies present after this time and consequently, long-term follow
      up is essential to the timely diagnosis of metachronous lesions. The predominant
      controversies surrounding panendoscopy involve the comparable diagnostic
      efficacies between endoscopic procedures and various radiologic studies. Although
      the operative complications reported for panendoscopy have been minimal, the
      expense is considerably greater than that of the respective radiologic
      alternatives. After a critical review of the literature, the use of endoscopy has
      been found to be superior to CXRs and barium swallows as the principal means of
      diagnosis of upper aerodigestive tract cancers. Specifically, bronchoscopy with
      bronchial washings should be obtained via passage of the bronchoscope through the
      endotracheal tube in order to decrease contamination. Positive washings are
      significant and demand further evaluation. Negative washings, on the other hand,
      yield little information.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396182
TI  - Autograft tragal and conchal palisade cartilage and perichondrium in
      tympanomastoid reconstruction.
AB  - Since Utech's introduction of cartilage as a columella in ear surgery in 1969, we
      have used tragal and conchal autografts for reconstruction of the tympanic
      membrane and the auditory canal wall in 13,000 cases. As large pieces of
      cartilage can twist in later years, we place palisaded cartilage fragments with
      perichondrium parallel to the manubrium of the malleus in type I tympanoplasties
      and in type II or III procedures parallel to the long process of the incus. The
      "annulus-stapes plate" in type III tympanoplasties replaces the function of the
      incus (and malleus), crossing the promontory and reducing adhesions. A
      "tunnelplasty" keeps the eustachian tube entrance open with the semiring of
      cartilage ("simmering") apposed to the inside of the annulus, reconstructing the
      tympanomeatal niche. The "architrave" created rests on the tensor tympani while
      the palisaded epitympanum and antrum plasty allows ventilation of the antrum.
      Mastoid obliteration is performed with an autogenous perichondrial transplant to
      which the palisaded incised cartilage portions adhere, adapting to the underlying
      structure.

PMID- 1396179
TI  - Transplantation of cultured premyelinating oligodendrocytes into normal and
      myelin-deficient rat brain.
AB  - Cultures of oligodendroglial cells at various stages of maturation, from
      progenitors to maturing oligodendrocytes, were prepared from neonatal rat brain
      primary cultures and then were prelabeled in the culture dish with the
      fluorescent dye, fast blue (FB). Single cell suspensions were grafted into normal
      or myelin-deficient rat brains. The normal as well as the myelin-deficient in
      vivo environment allowed cell survival, migration, and differentiation. The FB+
      cells expressed the oligodendroglial markers, glycerol phosphate dehydrogenase,
      galactocerebroside, and myelin basic protein. In the normal rat transplanted
      cells were identifiable at all times studied up to 24 weeks. Extensive migration
      of FB+ cells was observed in whole-brain sagittal sections. Our results show that
      the plasticity of oligodendroglia differentiation, extensively studied in vitro,
      can now be investigated in the normal and myelin-deficient in vivo environment.

PMID- 1396183
TI  - Malignant thyroid lymphoma presenting as acute airway obstruction.
AB  - Malignant thyroid lymphoma is an uncommon form of thyroid cancer which most
      commonly presents in elderly women. Most patients demonstrate a rapidly enlarging
      mass and may show tracheal deviation on chest roentgenogram. Radioisotopic
      scanning of the thyroid often demonstrates a "cold" or "cool" process of
      decreased uptake in the affected area. There is often an underlying lymphocytic
      thyroiditis process noted. Unfavorable prognosis is related to extracapsular
      extension, blood vessel wall infiltration, diffuse architectural pattern, and
      cervical lymph node involvement. We present two unusual cases of thyroid lymphoma
      presenting with acute airway obstruction and review the literature concerning
      this subject. One case presented a clinical and radiographic appearance similar
      to a prevertebral space abscess.

PMID- 1396186
TI  - Child abuse and neglect.

PMID- 1396185
TI  - Chondritis of the burned ear: a review.
AB  - Seventy-six patients with burns of the ears presented to the Western Pennsylvania
      Hospital Burn Trauma Center over a three year period. To prevent chondritis, all
      ears were treated prophylactically with periauricular hair shaving, daily
      cleaning, avoidance of pressure dressings and Sulfamylon Burn Cream. Chondritis
      developed in two patients. Aspects of auricular chondritis prevention and
      treatment are reviewed. Biology of the disease is discussed.

PMID- 1396184
TI  - Actinomycosis of the larynx.
AB  - Actinomycosis of the larynx is rare. Only seven cases have been reported in the
      literature. We report a case of actinomycosis of the larynx in a 63-year-old male
      following radiation therapy for laryngeal carcinoma. The diagnosis of
      actinomycosis can be made with a biopsy. It is important to distinguish infection
      from radionecrosis and recurrent carcinoma. Treatment consists of airway control
      and a prolonged course of antibiotics.

PMID- 1396187
TI  - Sexual abuse of children as seen at Kenyatta National Hospital.
AB  - A retrospective study of 21 sexually abused children admitted to the Kenyatta
      National Hospital, Nairobi, Kenya, between January 1984 and December 1985 is
      presented. The peak incidence of sexual abuse was in the age group of 10-15 years
      (38.1%) followed by the 5-9 years age group (28.6%). Strangers and people
      familiar to the child were equally implicated as assailants. Fourteen out of the
      twenty one (66.7%) victims, presented with injuries ranging from perineal tears
      (19%), vaginal tears (19%), recto-vaginal fistulae (RVP) (4.8%) and vesico
      vaginal-fistulae (VVF) and abdominal haematoma (4.8%). The victims presented to
      hospital within two days of the event usually accompanied by their mothers.

PMID- 1396188
TI  - Unintended conception and unwanted fertility in Gondar, Ethiopia.
AB  - This is a report on unintended conception and unwanted fertility in Gondar,
      Northwestern Ethiopia. The purpose of the study was to explore the extent of the
      problem and to inquire whether there is a need for fertility regulation. To this
      end, relatively numerous questions on reproductive history of women aged 15-49
      have been raised. Results showed that the proportion of abortion to delivery was
      0.3984 to 0.6016 and the ratio of unintended conception to intended conception
      was 0.4043 to 0.5957. The proportion of unwanted fertility to wanted was 0.4099
      to 0.5901. Mean desired interpregnancy interval was substantially higher than
      actual interpregnancy interval. The relatively high rate of abortion, high
      proportion of unintended conception and unwanted fertility combined with the wide
      difference between desired interpregnancy interval and current interpregnancy
      interval all point to the need for a policy that increases the capacity to
      regulate fertility.

PMID- 1396189
TI  - Neonatal morbidity and mortality at Kenyatta National Hospital newborn unit.
AB  - A six month prospective study of neonatal morbidity and mortality of the newborn
      unit (NBU) at Kenyatta National Hospital is presented. Of the 126 infants
      delivered in the maternity unit, 967 (30%) ended up in the NBU and 562 (59.8%)
      were low birth weight (LBW); 79.3% were appropriate for gestational age (AGA),
      19.9% were small for gestational age (SGA) while 1.8% were large for gestational
      age (LGA). The infants with birth weight of < 1500 g and gestation < 32 weeks had
      the worst prognosis with a mortality of 51.3% and 64.6% respectively. The major
      causes of morbidity and mortality were immaturity, respiratory distress,
      infections and perinatal asphyxia. The majority of the deaths (86.8%) occurred
      within the first week of life. The overall neonatal mortality for this period was
      24.6%, but 95.6% of the deaths were preterm while LBW in general contributed to
      93.5% of the deaths.

PMID- 1396190
TI  - Sickle cell leg ulcers in Ghana.
AB  - Twenty five (17 male, 8 Female) sickle cell disease patients with 30 leg ulcers
      were studied over a 3 year period (January 1985 to December 1987) to provide
      information on the pathogenesis, course and management. There were 23 patients
      with homozygous sickle cell and 2 patients with sickle cell haemoglobin C
      disease. The mean age was 28 years (range 15-44 years). An antecedent history of
      trauma was obtained in 40% of the patients and 96% had a previous history of leg
      ulcer. The major site affected (93%) was the skin around the malleoli. In 68% of
      the patients a single organism was isolated and the commonest bacteria were
      Pseudomonas species, Staphylococcus aureus, Proteus species and B haemolytic
      streptococci. The major complications encountered were equinovarus deformity
      (36%) and chronic periosteitis (32%). The main topical antimicrobial used was
      Eusol either alone (52%) or in combination with Metronidazole (32%) or honey
      (12%). Complete healing occurred in 40% of patients, partial healing with
      deterioration in 16% and no significant change in 44%. Admission and bed rest
      were the best determinants of complete healing of the chronic ulcers.

PMID- 1396191
TI  - Psychosocial effects of sickle cell disease among adolescents.
AB  - One hundred and thirty eight adolescents with Sickle Cell Disease responded to a
      semi-structured questionnaire with respect to their attitudes to Sickle Cell
      Disease. Bone pain was the most frequent reason for admission into the hospital.
      Those who had more than three hospital admission for either bone pain, blood
      transfusion or infection saw themselves as unhappy people. A sense of shame in
      public, inability to play games of their choice, fear of dying young, and fear of
      not achieving their goals in life were reasons given for unhappiness. Majority of
      them appreciated that their parents were concerned about their plight. The need
      for further research in the area of the attitudes of sicklers is discussed.

PMID- 1396193
TI  - Guided dilatation of urethral strictures.
AB  - Ten patients with pinhole urethral strictures were treated by introducing a
      flexible guide wire endoscopically through the stricture then passing flexible
      hollow dilators over the wire across the stricture. The procedure was successful
      in 9 out of 10 patients. It inflicts minimal trauma to the urethra and is
      recommended as a practical substitute for optical urethrotomy where the latter is
      not available.

PMID- 1396194
TI  - Stroke at the prime of life: a study of Nigerian Africans between the ages of 16
      and 45 years.
AB  - Sixty-seven patients (27.9%) between 16 and 45 years, out of 240 cases of stroke
      seen over 33 months were further studied with respect to stroke type,
      aetiological and social factors. The frequency of non-embolic cerebral infarction
      was 58.2%, cerebral embolism 7.5%; cerebral haemorrhage 17.9%; primary
      subarachnoid haemorrhage 11.9%. Hypertension was the commonest aetiological
      factor occurring in 35.8% of the cases. Cervical spine hyperflexion, stenosing
      carotid arteritis, cocaine ingestion, mitral valve prolapse, non-valvular atrial
      fibrillation and chorion cancer featured among other less frequent but important
      factors presenting different diagnostic problems. The frequency of unexplained
      stroke was under 12%. The authors suggest that previously encountered cervical
      spine trauma among young stroke cases represent underreporting and that the
      relationship between young age, grand-multiparity and non-valvular atrial
      fibrillation be further elucidated.

PMID- 1396195
TI  - Management of shoulder dystocia.
AB  - Shoulder dystocia is a rare obstetric emergency with which few clinicians have
      adequate experience. A case which was successfully managed is presented and
      current management procedures reviewed.

PMID- 1396197
TI  - Ministry of Health. Kenya National AIDS Control Programme. Guidelines for
      research proposals on HIV/AIDS.

PMID- 1396192
TI  - Protozoan infections and HIV-1 infection: a review.
AB  - Reactivation of latent infection is the principal mechanism relating Toxoplasma
      gondii and Pneumocystis carinii to HIV. Less common is reactivation in Leishmania
      donovani, Trypanosoma cruzi, and microsporidian infections. An impaired primary
      immune response occurs in all these infections, and also with Cryptosporidium and
      Isospora belli. Association of HIV infection with gut parasites including Giardia
      lamblia and Entamoeba histolytica, and also with Trichomonas vaginalis infection
      is likely to be related to sexual modes of contact that favour both HIV and the
      parasite. The severity of malaria is not definitely associated with HIV, but
      Plasmodium falciparum infection may favour more rapid evolution of the HIV
      infection. Both malaria and trichomoniasis favour HIV transmission; the former by
      necessitating blood transfusion, and the latter by enhancing viral transmission
      during sexual contact.

PMID- 1396198
TI  - Treatment of symptomatic trichomoniasis among adult women using oral
      nitroimidazoles.
AB  - Successful treatment of infections with Trichomonas vaginalis (TV) is difficult
      because of many confounding factors such as poor abstinence from sex during
      chemotherapy, lack of standardised chemotherapy, difficulties in understanding
      transmission patterns and low detection rates among infected individuals. The
      purpose of this study was to establish the present efficacy of the available
      drugs at their recommended single or double dosages for Kenya. Adult symptomatic
      females (age 17-39 years) with positive High Vaginal Swabs but without pregnancy
      were recruited into the study; and asked to swallow one of the following
      medicine: nimorazole 2G (Naxogin Farmitalia Carlo Erba, Italy), nimorazole 4G in
      two equally divided doses 24 hours apart (2GBD), nimorazole 3G, tinidazole 2G
      (Fasigyn, Pfizer Ltd) and ornidazole 1.5G (Tiberal, Roche, Switzerland). All
      patients were reviewed 48 hours after the drugs administration and 24 hours after
      the last dose for the group which received nimorazole 2GBD. 153 patients were
      recruited into the study. 121 came for follow up out of which 49 were dropped
      from the study for involvement in sexual intercourse leaving only 72 for the
      final analysis. Clinical cure was 100% for the group receiving nimorazole 2GBD
      and nimorazole 3G. Parasitological cure was highest for the group on nimorazole
      2GBD (100%) and lowest for the group on tinidazole (50%). Instruction to avoid
      sex during treatment were withheld from patients. This made it easier during the
      follow up to pick out and drop from the study those who had had sexual contact.

PMID- 1396196
TI  - The bacteriology of chronic suppurative otitis media.
AB  - Specimens obtained directly from the middle ear under direct vision from 40
      patients with chronic suppurative otitis media (CSOM) were investigated
      quantitatively and qualitatively for aerobes and anaerobes. Twenty one of the 40
      specimens yielded aerobes only, 17 yielded a mixed flora of anaerobes and aerobes
      while only one yielded anaerobes only and the remaining one was sterile.
      Bacteroides fragilis was the commonest anaerobe and the second single most common
      bacteria generally present in CSOM. Pseudomonas aeruginosa and Staphylococcus
      aureus were the dominant aerobic flora appearing in 17 and 14 out of 40 specimens
      respectively. All pathogens isolated were present in very high counts averaging
      10(8) ml of the exudate. The use of systemic anti-anaerobic drug combined with an
      anti-aerobic drug is worthy of a clinical trial.

PMID- 1396199
TI  - Truth management.

PMID- 1396200
TI  - Diagnosis doubtful: a ten year old follow-up.
AB  - In a period of one-year, 81 (1.7%) of the patients admitted to a Neuro
      Psychiatric Hospital, Aro, Abeokuta, were discharged undiagnosed. These patients
      were followed up during a 10 year period and sixty-two were ultimately diagnosed
      while 19 remained undiagnosed. Sixty-one patients of similar age and sex, treated
      at hospital during the same period who had a definite diagnosis were studied.
      Comparison of the clinical features of the two groups showed the absence of
      nuclear symptoms amongst the study schizophrenics compared with the controls.
      Among the depressives, the prominence of physical symptoms and agitation
      differentiated the study group from the controls. Out of the 19 patients who
      remained undiagnosed, 42.1% could not be traced, and 10.5% had become
      schizophrenic, and three patients (15%) had died. Review of the clinical features
      at the initial presentation showed that 29 (72.5%) out of the 40 initially
      undiagnosed schizophrenics could be placed in the diagnostic category using ICD9
      criteria.

PMID- 1396201
TI  - Acetylation status using hydralazine in African hypertensives at Kenyatta
      National Hospital.
AB  - In this study, the investigation of hydralazine acetylator phenotype was
      undertaken for the first time in African hypertensives at Kenyatta National
      Hospital. A total of 25 randomly selected patients with moderate to severe
      hypertension (diastolic pressure 105-130 mmHg), participated in the phenotyping
      study. The phenotyping was done by administering oral standard hydralazine dose
      of 150 mg/day in three divided doses. The 24 hour urinary MTP/hydralazine ratio
      was used to categorize patients into slow and fast acetylators. Of the patients
      studied 69.9% were slow acetylators while 30.4% were fast acetylators. The mean
      24 hour urinary MTP/hydralazine ratio for slow acetylators was 1.01 +/- 0.95.
      This was significantly different from the fast acetylators where the mean 24 hour
      urinary MTP/hydralazine ratio was 10.6 +/- 4.4 (P < 0.001). The acetylator
      phenotyping divided the patients into two distinct populations and no further
      arbitrary method was required to divide the patients into either group.

PMID- 1396202
TI  - Hemifacial pain and headache in gasseroma.
AB  - A case of severe disabling hemofacial pain in a Tanzanian African caused by
      gasseroma which was successfully removed is presented and the nature of the
      illness outlined. Intractable ticdouloureux is mainly due to vascular compression
      on the fifth cranial nerve or secondary to conditions to the nerve. Diagnosis of
      gasseroma is mainly by clinical history and examination.

PMID- 1396203
TI  - The operative key to preventing recurrence after sliding herniorrhaphy.

PMID- 1396204
TI  - Protein energy malnutrition: current status.

PMID- 1396205
TI  - The effect of protein energy malnutrition on morbidity and mortality due to
      measles at Kenyatta National Hospital, Nairobi (Kenya).
AB  - In a study of 7,631 cases referred to the infectious diseases hospital, Nairobi
      with a diagnosis of measles, 7,447 cases had the diagnosis confirmed. The overall
      mortality was 17.5 per 1000 cases with 43.51 of all the deaths occurring in all
      children less than 12 months of age. A nutritional analysis revealed that
      children whose weight were below 80 of the Harvard median of weight for age
      stayed in hospital longest and had the highest mortality rate. Measles continues
      to offer increasing challenge in spite of the intensive vaccination programme
      presently being carried out.

PMID- 1396206
TI  - Severe measles outbreak in western Kenya.
AB  - During a measles outbreak investigation in Siaya district clustering of many
      measles cases were found to be an important determinant for measles mortality. A
      high proportion of cases were under one year of age. Case fatality rates were
      higher than previously reported from Kenya, particularly among infants. Vaccine
      efficacy was 18%. Alternative ways of protecting infants are discussed.

PMID- 1396207
TI  - Hunger and malnutrition: the determinant of development: the case for Africa and
      its food and nutrition workers.
AB  - Hunger and malnutrition in Africa have been on the increase since 1960's reaching
      a climax in the 1980's when over 150 million people were affected by one form or
      another. Methods so far used to solve the problem do not seem to succeed, but the
      scientists and leaders in Africa could now take the opportunity to consider and
      act on the problem in their own way. The formation of an African food and
      nutrition group to work with others on the problems, could give an impetus to
      this kind of initiative. A call is made to all African food and nutrition workers
      to combine efforts to harness Africa resources, which have not been fully
      utilized in solving the problem.

PMID- 1396208
TI  - Plasma biochemical parameters in Nigerian children with protein energy
      malnutrition.
AB  - Eleven plasma biochemical parameters were estimated in a total of 28 children
      with protein-energy malnutrition (PEM): 7 children each category of marasmus,
      kwashiorkor, marasmic-kwashiorkor and undernutrition with ages between 8 and 48
      months. The estimations were performed on admission and 8 to 24 days after
      treatment at the Obafemi Awolowo University Teaching Hospitals Complex, Nigeria.
      Plasma sodium, potassium, chloride, bicarbonate and albumin levels were
      significantly (p < 0.05) higher after treatment than on admission. Calcium
      however, showed no significant change. Total protein and cholesterol were
      significantly (p < 0.05) raised after treatment for all the PEM types except
      undernutrition and kwashiorkor respectively. Globulin, urea and creatinine were
      significantly (p < 0.05) raised after treatment for kwashiorkor. These
      biochemical findings support the claims of clinical improvement in PEM children
      after a minimum of 18 days of treatment at the OAUTHC in Nigeria.

PMID- 1396209
TI  - Nosocomial bacterial infections among children with severe protein energy
      malnutrition.
AB  - The incidence of hospital acquired acute bacterial infections among 164 severely
      malnourished children admitted to the paediatric wards at the Muhimbili Medical
      Centre in Dar es Salaam were studied. On admission, ninety two per cent of the
      patients had at least one form of bacterial infection. During the subsequent two
      weeks hospital stay, 49% of the patients acquired a new infection. Septicaemia
      and urinary tract infection (UTI) were the commonest infections. Staphylococcus
      aureus was the commonest organism in the former, while gram negative organisms,
      Escherichia coli and Klebsiella species, were predominant in the latter.
      Pathogens similar to those found from patients were cultured from random samples
      taken from the floor, beds, towels, sinks and antiseptic containers in the wards.
      Sensitivity patterns of isolated pathogens to antimicrobial agents showed that S.
      aureus was highly sensitive to cloxacillin, erythromycin, and gentamicin, while
      the gram negative organisms were highly sensitive to gentamicin. Our study shows
      that the problem of nosocomial infection in paediatric wards requires urgent
      attention. There is a need to institute preventive measures including provision
      of proper nursing care, maintenance of sterile environment, and reduction of
      duration of hospital stay.

PMID- 1396210
TI  - Comparative aetiology of childhood diarrhoea in Kakamega and Kiambu Districts,
      Kenya.
AB  - Two hundred diarrhoea specimens collected during January to February 1988, from
      rural children aged 0 to 60 months in Kakamega District were examined for
      bacteria, parasites and rotavirus. The results were compared with a sample of 184
      diarrhoea specimens matched for month of collection, taken from data collected in
      the same manner from children in Kiambu District. The mean ages of children in
      the 2 samples did not differ significantly. There were significant differences in
      the prevalence of specific potential pathogens isolated in the 2 areas. Notably,
      A. lumbricoides and rotavirus were more common in Kakamega, while G. lamblia,
      Entamoeba histolytica, Trichomonas hominis, Cryptosporidium sp., Hymenolepis nana
      and EPEC were more common in Kiambu. There was no difference with respect to
      prevalence of Campylobacter sp. or Blastocystis hominis. Factors which were
      probably important in determining aetiological differences included climate,
      water sources, animal contact and crowding. The differences highlight the fact
      that general predictions about aetiology cannot be made from isolated studies.

PMID- 1396212
TI  - Sickness absenteeism in a Nigerian teaching hospital.
AB  - The sickness absence records of employees in a University Teaching Hospital in
      Nigeria were examined over a period of three years. The health records of the
      hospital workers showed a preponderance of junior and intermediate workers. An
      overall proportion of absentee workers was 15.8% with an average of 3 spells of
      sickness per year per absentee while the duration of sickness per absentee was
      5.6 days per year. The younger employees less than 35 years of age and those with
      short duration of employment with the hospital have significantly higher spells
      and duration of sickness absence than others. While a lower spell of sickness and
      duration of sickness absence were observed among nurses, senior employees
      especially doctors had no records of sickness absenteeism in any of the 3 years
      of study.

PMID- 1396211
TI  - Viral hepatitis in pregnancy.
AB  - Fifty pregnant women with viral hepatitis were compared with 31 non-pregnant
      women with viral hepatitis in a prospective case-control study. The two groups
      were matching except for the serum bilirubin level and area of residence. Seven
      pregnant women died while none of the control patients died and the difference
      between the two groups was significant. More than 80% of the deaths occurred in
      the third trimester and most of them were post-partum deaths. Except for a higher
      incidence of pre-term birth, the outcome of pregnancy in the case group was not
      affected. It is concluded that pregnancy is a risk factor which increases the
      mortality of viral hepatitis and that viral hepatitis does not affect the outcome
      of pregnancy except for pre-term birth.

PMID- 1396213
TI  - Clinical and pathological features of ovarian tumours in Rivers state of Nigeria.
AB  - The pattern and clinical features of 45 ovarian tumours seen in a Southern
      Nigeria hospital between 1984 and 1987 were examined. The results indicate that
      germ cell tumours are relatively more common in this part of Nigeria than in
      North America and Europe. A reduced incidence of surface epithelial tumours was
      also observed. Most patients with either benign or malignant tumours were less
      than 40 years old. Two of the five tumours associated with pregnancy were
      malignant. The ratio of benign to malignant tumours, presenting complaints of the
      patients and the late stage of most malignant tumours at the time of diagnosis
      were consistent with what has been observed in other parts of the world.

PMID- 1396214
TI  - Histological subtypes of non-Hodgkin's malignant lymphoma in Ibadan.
AB  - Immunohistologic analysis of 100 consecutive cases of non-Hodgkin's lymphomas
      (NHLs) from the Pathology Department of the University College Hospital, Ibadan,
      show that the majority (75%) of the NHLs are of B-cell origin. The high grade
      tumours constitute the bulk of these tumours with a paucity of follicular
      lymphomas. Low-grade lympho-plasmacytic/cytoid lymphomas are not uncommon. The
      possible role of the overstimulation of the B-cell immune system in the
      aetiopathogenesis of the B-cell NHL is highlighted. Further detailed studies to
      find out potential infective aetiological factors in the development of high
      grade B-cell lymphomas in the environment is suggested.

PMID- 1396215
TI  - Tuberculosis in a rural hospital in northern Kenya.
AB  - A 9-year survey on tuberculosis control at Sololo General Hospital (Marsabit
      District) is presented. 700 patients were treated and followed up from 1982 to
      1990. The paper deals with the major constraints of TB control in a nomadic
      population on the borderland with Ethiopia; it highlights the need of the short
      course regimen and the TB manyatta programme to increase the percentage of cured
      patients.

PMID- 1396216
TI  - Gonorrhoea neurosis.
AB  - In two years of clinical practice, the authors saw 47 cases of gonorrhoea of
      strictly psychological origin--25 patients with anxiety neurosis, 10 with
      hypochondriasis, 7 with depression, and 5 with paranoid reaction, 25 with
      impotence initially presented for surgical opinion rather than psychiatric
      assessment. Socio-demographic factors and 4 clinical details are given, including
      possible related factors, course, treatment and outcome. Liaison between the
      veneorologists, surgeons and psychiatrists is strongly advocated.

PMID- 1396217
TI  - Exercise-induced asthma (EIA) after walking: a case report.
AB  - A case in which exercise-induced asthma (EIA) was provoked at an intensity of
      less than 100 beats/min is discussed. EIA was provoked by a 12-minute walk test.
      Earlier tests using walking on other subjects had not produced such a result. It
      is therefore vital to teach asthmatics to monitor their pulmonary response at
      regular intervals to avert serious attacks in activities of daily living.

PMID- 1396218
TI  - Concurrent adenocarcinoma of the colon and chronic intestinal parasitoses: a case
      report.
AB  - A 25-year-old patient presented with recurrent bloody diarrhoea associated with
      intestinal parasitoses. Radiography and tissue histology confirmed the diagnosis
      of an annular colonic adenocarcinoma. The incidence and management of colonic
      malignancy in young Africans is discussed in the light of its described
      associationship with protozoal/helminthic parasitoses.

PMID- 1396219
TI  - Progress and development of fetal medicine.

PMID- 1396220
TI  - Care in early pregnancy.
AB  - This century has seen marked improvement in perinatal outcomes but prematurity
      remains a problem the world over. To improve these results requires more
      attention to early pregnancy or even pre-pregnancy care. Control of pre-existing
      conditions, improved social behavior in nutrition, smoking cessation and other
      factors are discussed.

PMID- 1396221
TI  - Training in perinatal care--management of patients in labour.
AB  - Training in perinatal care involves many different areas, and care around the
      time of labour forms a core part of training. Our senior residency programme
      involves 6 months supervised work in the labour ward. During this period,
      management of spontaneous, induced and augmented labour, methods of fetal
      monitoring and pain relief are taught. A log book and a check list are maintained
      to ensure the necessary manipulative and operative obstetric procedures have been
      followed. Limited scanning experience is provided to enable management of
      emergencies such as APH, multiple pregnancies, etc. Preparation and presentation
      of monthly statistics become a responsibility. Daily neonatal ward rounds are
      performed so that neonatal morbidity in relation to obstetric events are
      correlated. This exercise provides adequate knowledge to prognosticate and
      counsel patients whose babies are low birthweight or have malformations. Two to
      three new research projects are entrusted to trainees in order to acquire skills
      in writing research protocols, applications for research grants and later to
      enter research and write manuscripts. Discussion regarding research, working
      protocols and management problems are carried out after the daily ward rounds.
      Relevant reference papers or chapters are read, discussed and compiled in a file
      for further reading and for the benefit of other residents in training. This
      posting is followed or preceded by 6 months posting in ultrasound, high risk,
      medical disorder, diabetic and endocrine clinics. They also manage the antenatal
      and postnatal wards during these 6 months. At the end of 1 year training those
      interested in fetomaternal medicine do a further 2 years training in these areas
      at an advanced level.

PMID- 1396222
TI  - Postgraduate education in ultrasound diagnosis in obstetrics and gynaecology in
      Sweden.
AB  - The Swedish Society of Obstetrics and Gynaecology has set up principles for
      systematic postgraduate education in ultrasonography in obstetrics and
      gynaecology. The education is available at three levels: (1) a basic course; (2)
      an advanced course; and (3) special courses. The subjects included in each course
      are described. It is expected that this programme of formal education will lead
      to improvement in the Swedish gynaecologists' knowledge of ultrasonography.

PMID- 1396223
TI  - The training of a neonatologist.
AB  - A neonatologist must acquire the basic knowledge of a perinatologist through
      training in a perinatal centre with close obstetric collaboration. As a
      clinician, he/she must acquire competence in the medical care of critically-ill
      neonates through 3 years of neonatal experience following general paediatric
      training. As an administrator, skills are required in nursery management,
      regional planning, audit and follow-up of high-risk survivors. Skills are
      required as an educator for medical/nursing staff and the community. Training as
      a researcher enables appreciation of perinatal research and appropriate
      application of scientific advances to clinical practice. He/she must become a
      person who cares, able to understand psychosocial and ethical issues in
      neonatology.

PMID- 1396224
TI  - Significance of chorioamnionitis.
AB  - In preterm deliveries, we have reported a high incidence (30-50%) of histologic
      chorioamnionitis (CAM) in the placenta. There is little evidence about the
      effects of CAM on preterm infants. We investigated the levels of complements and
      cytokines in the cord blood, the pathological nature of the placenta, the L/S
      ratio of gastric and tracheal aspirate of each preterm infant at birth, and
      assessed the biological effects of CAM on them. CAM stimulates the immunological
      system by cytokine production (IL6 and IL8) and complement activation in the
      fetus. It has been suggested that CAM may be one of the factor accelerating fetal
      maturation of the immunological system such as complement activation and
      immunoglobulin production, and of surfactant synthesis in the lung. On the
      contrary, CAM may damage the structures along the lining cells in the airway by
      accumulating polymorphonuclear cells of the infants with Wilson-Mikity syndrome.

PMID- 1396225
TI  - Perinatal viral infections.
AB  - Among the TORCH agents, the occurrence of rubella and human T-lymphotropic virus
      type 1 (HTLV-1) in Japan were studied. Rubella epidemics occurred throughout
      Japan from 1964 to 1969 and from 1975 to 1979. Low prevalences of CRS were
      observed in northeastern Japan, and high prevalences in southwestern Japan, with
      the highest in Okinawa. These conditions could be explained by the lower rate of
      rubella H1 antibody in the female population of southwestern Japan. Time of
      maternal rubella was in the gestational age interval from 26 to 57 days for
      cataract, from 25 to 62 days for heart disease and from 16 to 131 days for
      deafness. HTLV-1 is the causative agent of adult T-cell leukemia. Main route of
      transmission of this virus is mother-to-child transmission, through breast milk.
      Among the 311 mother-child pairs in Okinawa, 65 mothers (20.9%) and 10 children
      (3.2%) were seropositive for HTLV-1. Ten (15.4%) of the 65 seropositive mothers
      had seropositive children. These children had acquired their HTLV-1 antibodies by
      the age of 3 years. A significant difference existed between the prevalence rate
      of HTLV-1 antibodies in mothers and children.

PMID- 1396226
TI  - Immunotherapy in perinatal infection.
AB  - Though intravenous immunoglobulin (IVIG) have been shown to be beneficial in the
      treatment of some perinatal viral infections like varicella and possibly
      cytomegalovirus. The main thrust of interest has been directed towards the
      prevention and treatment of perinatal bacterial infections. This paper reviews
      literature published thus far (October 1991) on the use of IVIG in perinatal
      sepsis.

PMID- 1396228
TI  - Effective measures for the prevention of late abortions and premature births.
AB  - After a retrospective study, more than 70% of premature births have been caused
      by ascending infections. With the use of a specially concerted diagnostic and
      therapeutic prevention programme, a reduction of 30% in very low birthweight
      prematures (less than 1500 g) has been achieved in in-hospital care and of about
      50% in outpatient care.

PMID- 1396227
TI  - Autoimmune thrombocytopenic purpura: maternal and fetal disease.
AB  - We have followed up 63 pregnancies in women with autoimmune thrombocytopenic
      purpura (ATP). Of these, 15 were previously splenectomized. The characteristics
      of the sample can be summed up as follows: average age 27 years (17-41);
      platelets at the beginning of pregnancy, mean 129.5 x 10(9)/l (range 16-488);
      platelets at delivery, mean 133 x 10(9)/l (range 8-477); PA-IgG at delivery, mean
      320 ng IgG/10(7) platelets (range 10-1000); SPB-IgG at delivery, mean 262 ng
      IgG/10(7) platelets (range 10-1000). There were 30 spontaneous deliveries and 33
      cesarean sections. Forty-two newborns had a platelet count within the normal
      range while nine had a platelet count less than or equal to 150 x 10(9)/l, while
      six had less than or equal to 100 x 10(9)/l and a further six less than or equal
      to 50 x 10(9)/l. The aim of this study is the evaluation of maternal risk and of
      possible feto-neonatal thrombocytopenia at birth. In this regard, the following
      parameters were considered: previous maternal splenectomy; the platelet count at
      the beginning of pregnancy; the platelet count and the titres of PA-IgG and SPB
      IgG at delivery. Preliminary statistical evaluation of these parameters enabled
      us to identify a risk score. From this it was possible to obtain an optimum
      management of the final stage of pregnancy regarding the therapeutic approach and
      the timing of delivery.

PMID- 1396229
TI  - The role of fetal blood sampling in prenatal diagnosis.
AB  - Fetal blood sampling via cordocentesis is being used with increased frequency. In
      our clinic, 125 fetal blood samplings (109 patients) have been performed for
      evaluation of a variety of clinical situations. Our experience confirms the
      efficacy of the procedure and suggests that it may be an important tool for fetal
      assessment.

PMID- 1396230
TI  - Effect of atrial natriuretic factor (ANF) on water homeostasis of the neonate.
AB  - Atrial natriuretic factor (ANF) has been well known as a potent natriuretic
      peptide. The purpose of this study was to clarify the physiological role of ANF
      in neonates. We designed two types of study to investigate the role of ANF in
      neonates. (i) The role of ANF in neonatal fluid homeostasis; (ii) ANF and
      spontaneous diuresis. As a result, ANF may be released to control the
      extracellular volume and may have a role in the complex mechanisms that regulate
      the water homeostasis in neonates.

PMID- 1396231
TI  - Perinatal adaptation of the cardiovascular system.
AB  - The perinatal changes in the cardiovascular system were studied in fetal rats.
      The changes in the cardiovascular system occurred earlier than in humans. The
      ductus arteriosus closes in the rat in one and a half hours.

PMID- 1396232
TI  - Neurological maladaptation in the neonate.
AB  - The development of neuronal dendrites dramatically changes in the medullary
      respiratory centers from prenatal to postnatal periods. The number of spines
      increases with gestation and decreases rapidly after birth in controls, but
      persist in sudden infant death syndrome patients. These abnormalities including
      neurotransmitters may cause a maladaptation in the development of
      cardiorespiratory control.

PMID- 1396233
TI  - The role of insulin in fetal growth.
AB  - Disturbances in fetal insulin secretion are associated with abnormalities in
      fetal growth in a variety of species: excessive insulin secretion can lead to
      fetal macrosomia while fetal hypoinsulinaemia invariably causes fetal growth
      retardation. Fetal insulin deficiency caused by pancreatectomy (PX) of the sheep
      fetus leads to reduced body weight, crown-rump length and limb lengths at
      delivery near term. The growth rate in utero fell by 40-50% after PX and could be
      restored to normal values by insulin replacement treatment. These changes in
      growth were accompanied by reductions of 30-40% in the rates of umbilical uptake,
      utilization and oxidation of glucose by the sheep fetus. Insulin is therefore a
      physiological regulator of fetal growth and acts in part by stimulating the
      cellular uptake of glucose and its preferential use for oxidative metabolism in
      the fetal tissues.

PMID- 1396235
TI  - Intrauterine feeding of the growth retarded fetus: can we help?
AB  - Intrauterine feeding of the growth retarded fetus appears an attractive
      therapeutic possibility. However the factors which determine the reversibility of
      intrauterine growth retardation are poorly understood. While fetal substrate
      supply is the final common pathway by which many factors restrict fetal growth,
      improving fetal substrate supply does not always lead to improved fetal growth.
      Similarly, fetal substrate supply is an important regulator of fetal endocrine
      status, such as circulating IGF-1 levels, but again, improving fetal substrate
      supply does not always alter fetal endocrine status or fetal growth. The
      relationship between substrate supply, endocrine status and growth is regulated
      in a complex way by placental function. Understanding the role of the placenta in
      this regulation is essential if in the future we are to help the growth retarded
      fetus.

PMID- 1396234
TI  - Fetal amino acids in normal pregnancies and in pregnancies complicated by
      intrauterine growth retardation.
AB  - Plasma amino acid concentrations were measured in normal (AGA) and intrauterine
      growth retarded (IUGR) percutaneous umbilical blood sampling (PUBS) performed for
      prenatal diagnosis or at elective cesarean section. IUGR fetuses present
      significantly lower concentrations of most amino acids, with a significant
      reduction of the umbilical veno-arterial difference for total alpha-amino
      nitrogen. These findings are present early in growth retarded fetuses and may be
      potentially responsible for the growth retardation.

PMID- 1396236
TI  - Perinatal computing design criteria for high tech support for clinical image
      services.

PMID- 1396237
TI  - Perinatal care in China.
AB  - China has a birth rate of 20/1000, maternal mortality of 48.8/100,000, perinatal
      mortality of 15-20/1000 in cities, and 30-35/1000 in rural areas, infant
      mortality of 34.68/1000 and a LWB rate of 6%. Among LWBI 50-60% are SGA. As a
      result the prematurity rate is also quite low, 3-4%, and the rate of VLBWI is
      only 0.3-0.4%. Therefore, attention should be paid first to bigger birth weight
      groups. Regionalized perinatal care is important in the cities, but the rural
      areas suffer more from low staffing levels and poor transportation. In view of
      the vast areas which are in need of techniques and the uneveness of the
      situation, sense of appropriate technology is very important. B-ultrasonic
      scanner versus gravidogram, FHR monitoring versus monitoring of fetal movement,
      and methods of keeping babies warm are discussed as examples.

PMID- 1396239
TI  - Frontiers in perinatal medicine.
AB  - A few of the topics of particular interest in perinatal medicine such as
      surfactants, erythropoietin, cordocentesis and computer assisted decision support
      are briefly reviewed. Asphyxia and oxygen toxicity are discussed as is the
      increase in the formation of free radicals which is part of reoxygenation. The
      infinitely larger problem of the poor in developing countries can best be
      improved--at least partially--by extending family planning techniques
      universally, otherwise the population explosion will counteract any other
      improvements.

PMID- 1396238
TI  - Training program in Japan for health caretakers from developing countries.
AB  - In 1979, the International Center for Medical Research was organized in Kobe
      University School of Medicine and promoted the scientific cooperation through
      invitation of foreign scientists from developing countries as the Core University
      of Medical Science of Japan Society for the Promotion of Science (JSPS).
      Perinatal medicine is one of the main subjects in this program and we have
      accepted more than thirty neonatologists from Indonesia, Philippines, Thailand
      and other developing countries.

PMID- 1396240
TI  - Primary health care and the perinatal period.

PMID- 1396241
TI  - HIV in women.
AB  - There are three patterns of HIV infection and AIDS. In industrial countries
      infection is between homosexual and bisexual males and intravenous drug users.
      Relatively few women are infected but the numbers are increasing. In sub-Saharan
      Africa the infection is heterosexual. More women are infected. AIDS incidence in
      other countries is low. Twenty-five percent of babies born to HIV positive women
      will be infected. Testing of infants at birth is difficult because of placental
      transmission of antibodies. Anonymous antenatal testing is important to establish
      prevalence which varies greatly in different areas. HIV infection is unique
      because of the social stigma, lack of vaccine and lack of effective therapy.
      There are profound social and psychological implications for the woman, her
      partner and her family. Therefore, a high level of caring and mature
      professionalism is required by all involved staff.

PMID- 1396242
TI  - Clinical presentation of HIV/AIDS in the high risk neonate in Zambia.
AB  - A prospective case series study was conducted Jan 1991-Oct 1991 on 108 neonates
      admitted to NICU, Lusaka. 90 patients satisfied inclusion criteria, 45 cases and
      45 controls. Symptomatic seropositive babies born to seropositive mothers
      presented with failure to thrive, fever, persistent or recurrent thrush, severe
      Sepsis and large liver. Tendency to prematurity among cases was high. Diarrhoea,
      Sepsis and Haemolytic Anaemia appear to be terminal signs. Neonates suffer the
      most aggressive form of HIV/AIDS, with symptomatic cases dying 3-4/52 of onset of
      symptoms. Over one quarter of the mothers were symptomatic. Congenital
      malformations and Lymphadenopathy were not significantly associated. Microcephaly
      occurred in association with failure to thrive and was not an isolated finding.

PMID- 1396244
TI  - Management of pregnancy of HIV infected woman.
AB  - The first case of HIV carrier pregnancy in Japan is reported. Fortunately this
      resulted in no apparent transmission of HIV to the baby and no manifestation of
      AIDS symptoms in the mother.

PMID- 1396243
TI  - Problems of AIDS in India especially in women.
AB  - According to the World Health Organisation survey, 3 million women are already
      infected with HIV all over the World, but in India the problem of AIDS as a whole
      is not that acute especially in women. At least it is not that alarming. India,
      having a very high incidence of STD, it will not take much time for the spread of
      the HIV infection. No case of mother-to-infant transmission of HIV and resultant
      clinical disease in the neonate and children has as yet been reported in India.
      Infected babies, however, face a short life--nearly all die before reaching 2
      years of age. Breast feeding is not a significant means of transmitting AIDS. The
      disease can spread only through sexual contact, use of infected syringe or
      transfusion of infected blood. Therefore, doctors, nurses and other paramedical
      staff in hospitals who may have to deal with AIDS patients need not fear the
      virus if they take adequate precautions. There is no known curative treatment for
      HIV infection causing AIDS, but improving literacy, avoiding sexual promiscuity
      and using condoms in heterosexual intercourse are positive steps in keeping HIV
      infection at a considerably low level.

PMID- 1396245
TI  - Hydrops fetalis caused by severe alpha-thalassemia.
AB  - Alpha-thalassemia is a prevalent condition in South East Asia and spreading
      because of increasing immigration. Hemodynamic study of Hb Bart's hydrops
      fetalis, the most severe form of alpha-thalassemia, showed the fetuses were in a
      hyperdynamic circulatory state and were also more acidotic, hypoxic, and
      hypercarvic than normal fetuses. The most common molecular defects of Hb Bart's
      hydrops fetalis was the Southeast Asia type deletion. Prenatal diagnosis of Hb
      Bart's hydrops fetalis and HbH diseases has been achieved using chorionic villi
      sampling or fetal blood sampling.

PMID- 1396246
TI  - Diagnosis and therapy in Rh-incompatibility.

PMID- 1396247
TI  - Intrauterine treatment on non-immune hydrops fetalis.
AB  - In 51 cases with non-immunologic hydrops fetalis (NIHF), perinatal management was
      performed based on our protocol. Twenty-two cases were treated by albumin and/or
      packed red cell (PRC) injection into the fetal abdominal cavity, and 9 cases by
      transplacental digitalization. Among the cases treated by albumin and/or PRC
      injection, 6 of 8 cases without pleural effusion recovered in utero, and all 6
      cases are alive. However, of 14 cases with pleural effusion, none recovered in
      utero, and only one case is alive. Of 9 cases treated by transplacental
      digitalization, 2 cases recovered in utero, and only one case is alive. All
      fetuses with congenital heart anomaly died. This evidence indicates that albumin
      and/or PRC injection into the fetal abdominal cavity is an effective procedure
      for in utero treatment of NIHF without pleural effusion, but suggests that in
      NIHF resulting from either congenital heart anomaly and/or heart failure, the
      survival rate may not be increased by transplacental digitalization.

PMID- 1396248
TI  - Longitudinal measurements of fetal heart rate (FHR) monitoring in second
      trimester.
AB  - We investigated the possibility of clinical diagnosis of preterm fetal well-being
      in the second trimester using the duration of LTVs of less than 4.5 beats/min and
      characteristic FHR acceleration. Fetuses between 24 and 32 weeks gestation,
      unlike near-term fetuses are seldom quiet and therefore the prolonged absence of
      fetal movement may be the best indicator of a sick fetus at these gestational
      ages. The amplitude and duration of the acceleration of the FHR were also
      clinically useful diagnostic tools for fetus well-being during the second
      trimester.

PMID- 1396249
TI  - The role of Doppler technology in the evaluation of fetal hypoxia.
AB  - Failing intrauterine support to the fetus can lead to intrauterine growth
      retardation (IUGR) and hypoxia and it is associated with a high risk of perinatal
      morbidity and mortality. The main effects of moderate to severe hypoxia on the
      fetus are different degrees of blood flow redistribution and reduction of oxygen
      consumption to maintain oxygen delivery to the central organs at the expenses of
      peripheral organs. The redistribution results in a 'brain sparing' effect.
      Recently, a Doppler ultrasonic technology (continuous wave, pulsed wave and
      colour flow imaging) has been developed for the non invasive measurement of flow.
      Doppler velocimetry detects the flow velocity waveform (FVW) which reflects the
      cardiac output, the vascular compliance and the resistance to the flow in a
      defined point of the vessel. Velocity waveform indices or even simpler criteria,
      such as the presence or absence of diastolic flow or flow reverse during
      diastole, have been applied to a number of fetal vessels. A significant
      relationship exists between blood oxygen, systemic lactic acidosis (determined by
      cordocentesis) and increase PI values in umbilical artery (UA), thoracic aorta
      (TA) and renal artery (RA). Moreover, in experimental animals during steady state
      hypoxia, several cardiovascular parameters are affected (heart rate/cardiac
      output decreases and blood pressure increases) while placental flow don't show a
      significant variation thus suggesting a raise in placental vascular resistance.
      Redistribution of the flow may be reliably evaluated by the cerebroplacental
      ratio (i.e. ratio between PI of MCA and PI of UA, c/p).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1396250
TI  - Fetal and neonatal cerebral oxygen monitoring with NIRS: theory and practice.
AB  - Near infra-red spectroscopy (NIRS) is a comparatively new method for monitoring
      the oxygenation in blood and tissue in the brain of the fetus and the neonate.
      Absorption of light in the wavelength range 700-1000 nm through such tissue is
      measured, which is then used to calculate changes in the concentration of
      cerebral oxygenated and de-oxygenated haemoglobin (HbO2 and Hb) and hence
      cerebral blood volume (CBV). Studies carried out on several groups of newborn
      babies have shown clear changes in HbO, Hb and CBV with hypoxia and bradycardia.
      These changes may well have implications in the occurrence of hypoxic/ischaemic
      brain injury. Intra partum NIR measurements on the fetal brain have demonstrated
      clear changes in HbO2, Hb and CBVm, coinciding with the onset of contractions.

PMID- 1396251
TI  - Intrauterine fetal reanimation in acute intrapartum fetal distress.
AB  - Uterine contractions during labour may produce acute intrapartum fetal distress.
      Intrauterine fetal reanimation is possible by reducing the strength of uterine
      contractions. Betamimetic therapy appears successful for this.

PMID- 1396253
TI  - Prenatal prevention of respiratory distress syndrome: new pharmacologic
      approaches.
AB  - A deficit of lung surfactant is known to be involved in the pathophysiology of
      the respiratory distress syndrome of the neonate (RDS), which is still
      responsible of about one fourth of total neonatal mortality. It has been well
      documented that maternal administration of corticosteroids enhances fetal lung
      maturity, promoting synthesis of surfactants and altering also the structure of
      the lung parenchyma. Although the beneficial effects of corticosteroids have been
      substantiated by a number of experimental evidences and clinical studies, about
      10% of the treated neonates remains affected by RDS. Corticosteroids affect the
      composition of lung parenchyma, by increasing elastin content and by decreasing
      alveolo-capillary permeability to serum proteins. Since thyrotropic releasing
      hormone (TRH) has been shown to potentiate the effects of corticosteroids a
      combination of the two drugs may be the treatment of choice for prenatal
      prevention of RDS.

PMID- 1396252
TI  - A prospective, randomized trial of early versus late administration of a single
      dose of surfactant-TA.
AB  - Thirty-two neonates weighing 500-1500 g with documented surfactant deficiency and
      without evidence of severe birth asphyxia, infection, prolonged rupture of
      membranes greater than or equal to 72 h, or oligohydramnios were randomly
      assigned to receive a single intratracheal dose of surfactant-TA (100 mg/kg)
      either within 30 min of birth (n = 16, early group) or at 6 h of age (n = 16,
      late group). By 6 h of age, all neonates of the late group had moderate/severe
      RDS, while none of the neonates of the early group had either clinical or
      radiological respiratory distress syndrome. The incidence of bronchopulmonary
      dysplasia was significantly lower in survivors of the early group than those of
      the late group (1/15 versus 7/14, a 43% reduction with a 95% confidence interval
      of 14-72%, P = 0.025). These beneficial effects of early surfactant treatment
      remained after controlling for the various confounding factors in the logistic
      models.

PMID- 1396254
TI  - Patent ductus arteriosus: how important to which babies?
AB  - An overview is presented of 21 randomised controlled trials of either surgical
      closure of the ductus arteriosus or indomethacin therapy in preterm infants. All
      trials included backup treatment if the ductus arteriosus persisted. Overall,
      there is no significant effect on mortality or chronic lung disease. In trials
      treating at a presymptomatic stage, there is a trend to reduce the incidence of
      chronic lung disease. Early treatment with indomethacin reduces the incidence of
      periventricular haemorrhage. An ultrasound study of 110 very low birth weight
      infants showed ductus arteriosus size at 3 days to be related to factors
      reflecting the infants' condition (ventilation indices, blood product
      administration), but not to birth weight or gestational age. Infants with a
      moderate to large ductus arteriosus at 3 days had a significantly lower blood
      pressure from 12 h of age onwards than those with a closed or small ductuses.

PMID- 1396255
TI  - Advances in mechanical ventilation: high frequency ventilation.
AB  - High frequency oscillatory ventilation (HFOV) is a technique in which a small
      tidal volume of airway gas is vibrated by moving a piston at an extremely fast
      rate (15 Hz). By this technique infants are ventilated in less traumatic ways
      compared to the conventional mechanical ventilation (CMV). The control study
      performed in Japan showed the efficacy and safety of HFOV compared to CMV.

PMID- 1396256
TI  - The use of high-frequency oscillatory ventilation (HFOV) and extracorporeal
      membrane oxygenation (ECMO) in the management of the term/near term infant with
      respiratory failure.
AB  - The use of high-frequency oscillatory ventilation (HFOV) was evaluated as a
      rescue intervention in 122 consecutive infants meeting criteria for
      extracorporeal membrane oxygenation (ECMO). Fifty-three percent responded to HFOV
      and never required ECMO, 3/65 died. Infants who ultimately required ECMO had
      lower aortic and pulmonary peak flow velocities, and lower pulmonary
      acceleration, circumferential fiber shortening and shortening fraction than those
      who were successfully managed with HFOV. The use of HFOV with an appropriate
      strategy decreased the need for ECMO in this patient population.

PMID- 1396257
TI  - Rationale for and work of the Perinatal Trials Service.
AB  - The Perinatal Trials Service provides a service to busy clinicians who wish to
      mount large simple-in-design randomized trials. The trials aim to identify
      moderate, but clinically useful, effects of promising treatments for the most
      important problems in perinatal care. A combination of a flexible five-person
      core resource and a cadre of staff employed to work on specific trials allows a
      programme of trials to be conducted successfully and efficiently. The Perinatal
      Trials Service has three main areas of work: prevention and treatment of
      immaturity and its consequent morbidity; identification and management of the
      compromised fetus or baby; and prevention and treatment of maternal morbidity.
      Examples of projects from each area are described.

PMID- 1396258
TI  - Evaluation of different policies for the management of labour.
AB  - Various policies of management of prolonged labour have been proposed to prevent
      its two main consequences--caesarean section and fetal distress. Two randomised
      controlled trials were organised; the first to assess the value of amniotomy with
      oxytocin compared to a more conservative approach. The second trial compared the
      effect of continuous professional support during labour with the intermittent
      presence of a member of staff. These were multicentre studies in several
      countries of Europe. Preliminary results of early amniotomy suggested no
      difference in the rate of operative delivery. Continuous professional support was
      associated with a significant reduction in operative deliveries.

PMID- 1396259
TI  - Multicentre collaboration in perinatal trials in Canada.
AB  - From a request of the Ministry of Health, the Canadian Association of Professors
      of Obstetrics and Gynecology and the Medical Research Council played a leadership
      role in convening perinatal investigators of all 16 university departments. The
      consensus was reached that the best means to improve the health of Canadians was
      to treat and/or prevent prematurity. In the last 10 years, several multicentre
      clinical trials were designed and carried out on perinatal interventions. This
      multicentre Canadian collaboration has recently evolved in the formation of a
      permanent perinatal clinical trial network of more than 100 members.

PMID- 1396260
TI  - Readiness of Japan to participate in international collaborative studies.
AB  - A significant improvement has been achieved in perinatal mortality figures during
      the last decade in Japan with a neonatal mortality rate of 2.6 and a stillbirth
      rate of 4.1 for 1989. With its unique obstetric and neonatal services, there are
      advantages and also disadvantages in respect of clinical and basic research. The
      outlook for Japanese neonatal medicine is shown and the prospects for
      international collaborative studies in the future are given.

PMID- 1396261
TI  - Randomized clinical trials in perinatology in Latin America.
AB  - Latin America needs means to obtain accurate figures about its health conditions
      in order to apply its resources to priority areas. In addition, health actions
      must be carefully evaluated to assess their impact, operation and costs. The
      randomized clinical trial (RCT) is the only design able to show the effectiveness
      of interventions of moderate effect. Also, it gives appropriate information about
      the expected effect of the interventions and implies an expediate implementation
      of interventions in the same places where the project has been performed. In a
      review of RCTs performed in Latin America on perinatal medicine it can be
      concluded that some of the focus of research is irrelevant to the region and
      there is not an orientation towards the cooperative solution of predominant
      problems in the area. It is imperative for researchers, in Latin America to
      initiate joint activities in order to assess which are the research priorities of
      the area, to focus their research on these priorities and to join their efforts
      in collaborative studies.

PMID- 1396262
TI  - Do breast milk derived hormones play a role in neonatal development?
AB  - Many hormones and several growth factors are present in significant
      concentrations in breast milk. That these substances are of physiologic
      significance has been suggested by many investigators. This review summarizes the
      biological roles of thyroid hormones and epidermal growth factor (EGF) derived
      from breast milk in a variety of developing mammals.

PMID- 1396263
TI  - Trace elements and mineral requirements for very low birth weight infants in
      rickets of prematurity.
AB  - To establish mineral and trace element requirements for very low birth it is
      important to prevent bone mineral disorder. Those infants fed mother's milk only
      are thought to be at higher risk of this disorder. Both calcium and phosphorus
      supplementation were thought to be needed to prevent it. Copper and zinc are
      important as cofactors of major enzymes involved in the synthesis of collagen.
      These trace elements especially zinc may not be enough for very low birth weight
      infants fed mother's milk. At present however the relationship between these
      trace elements and minerals, and bone metabolic disease in preterm infants is not
      completely clear.

PMID- 1396264
TI  - Fortified preterm human milk for very low birth weight infants.
AB  - We studied the nutritional effects of two types of human milk fortifiers for very
      low birth weight infants. These studies suggest that fortified human milk
      provides nutritional advantages for very low birth weight infants. However,
      providing calcium and phosphorus with supplementation is necessary for the
      improvement of bone density.

PMID- 1396265
TI  - Is mother's milk the most suitable food for very low birth weight infants?
AB  - Human milk feeding (HMF) as compared with formula feeding (FF) has the advantage
      of more effective utilization of proteins, fat, minerals and trace elements. HMF
      provides passive immunologic protection and active immunostimulation. It prevents
      the VLBWI from antigenic and toxic loads. The disadvantage of HMF is the high
      volume required tomeet the energy and protein needs of the VLBWI and the growing
      potential risk of AIDS, hepatitis and cytomegaly infections which makes human
      milk banking increasingly difficult. The current concept of VLBWI formula feeding
      (FF) is based on high protein, energy and mineral concentrations to compensate
      for the lower biological value, for lower bioavailability and for side effects
      related to the antigenicity of food proteins. FF as compared with HMF results is
      increased mineral and water retention, in high renal load and in a completely
      different body composition. The risk of necrotizing enteritis is significantly
      higher. All this has to be considered a challenge to further adapt LBWI formulas
      to the amino acid composition of human milk protein to induce bifidogenic effects
      and to provide sufficient amounts of essential fatty acids and carbohydrates
      which serve as building stones for normal brain development.

PMID- 1396266
TI  - Reproductive health: a global overview.
AB  - A global overview of reproductive health outlines major challenges for action.
      Worldwide, 60 million to 80 million couples suffer from infertility. At the same
      time, there is a striking unmet need for contraception in developing countries.
      Unsafe abortion practices result in between 115,000 and 204,000 deaths each year.
      Female genital mutilation in one form or another continues to exist in around 40
      countries. A second generation of organisms has now made sexually transmitted
      diseases the most common group of notifiable diseases in most countries. For the
      year 2000, it is projected that there will be a cumulative total of about 40
      million HIV infections in men, women and children. About half a million women die
      each year because of complications related to pregnancy and childbirth. A total
      of about 15 million infants and children die annually, mostly from preventable
      childhood diseases. At least 17% of all babies in developing countries are born
      with a low birth weight.

PMID- 1396267
TI  - Composition of premature breast-milk during lactation: constant digestible
      protein content (as in full term milk).
AB  - There is much discussion about the protein requirements of (very) preterm
      infants. The protein content of breast milk plays an important role in this
      discussion. For this reason, we took a close look at the protein content and its
      composition in premature breast milk. Complete 24 h expressions-were examined
      using the Kjedahl method, GPC, SDS-PAGGE and nephelometric detection of sIgA.
      Colostrum of premature breast milk contains a large amount of undigestible
      proteins, up to 70% of true protein, which decreases to 20-40% in transitory and
      mature preterm milk. The NPN fraction of mature preterm breast milk was,
      dependent on the degree of prematurity 20-25%; increasing during lactation from
      about 18% to 22-26%. This means that, depending on the lactation period only 30
      60% of the total protein content of breast milk is available for body protein
      synthesis. In absolute amounts, digestible protein is reasonably stable during
      lactation.

PMID- 1396268
TI  - Antenatal diagnosis of fetal abnormality by ultrasonic real time scanner.
AB  - Recent progress in antenatal diagnosis has made it possible to detect most fetal
      malformations which can be treated and cured by neonatal surgery. In this study
      an analysis of antenatal diagnosis by ultrasonography in the author's clinic is
      reported.

PMID- 1396270
TI  - Esophageal atresia (T-E fistula): an index for neonatal surgery.
AB  - During the period 1978-1990 (12.5 years), 929 neonatal general surgical
      emergencies were treated at the Seoul National University Children's Hospital.
      There were 308 anorectal malformations, 128 atresia/stenosis of the gut, 125
      neonatal Hirschsprung's disease, 75 gastroschisis and 67 esophageal atresias. The
      highest operative mortality rate of 26.9% was experienced in esophageal atresia
      with or without tracheo-esophageal atresia. Problems in respiratory care and
      surgical technical failure were the main causes of failure. Esophageal atresia
      can be used as an index for the status of neonatal surgical care since analysis
      of mortality of other operations indicates a similar but less exaggerated
      pattern.

PMID- 1396269
TI  - Antenatally detected ovarian cysts--a therapeutic dilemma.
AB  - Twenty-four instances of ovarian cysts detected antenatally are reported. Most
      cysts were functional in origin, histologically benign simple cysts. Pregnancy
      was clinically uncomplicated in all, followed by a spontaneous vaginal delivery
      in 20 cases between the 33rd and 41st week, four neonates were delivered by a
      cesarean section for obstetrical reasons. Nine cysts more than 5 cm in diameter
      at birth were treated surgically. The operative indications were as follows; 5
      neonates had clinical symptoms caused by abdominal distention or vomiting. The
      remaining four showed a sign of hemorrhage following torsion. Thirteen cysts less
      than 5 cm in diameter, and two cysts more than 5 cm in diameter began to regress
      spontaneously within 6 months after birth and finally 10 of them disappeared
      between 2 weeks and 2 years.

PMID- 1396271
TI  - Prenatal diagnosis of congenital diaphragmatic hernia and perinatal care:
      assessment of lung hypoplasia.
AB  - To assess the severity of lung hypoplasia, we have attempted to measure the lung
      thorax transverse area ratio (L/T) by using ultrasonic echography and to select
      immediate surgery after delivery by caesarean section. The evaluation of L/T for
      an index of lung hypoplasia was made by arterial blood gas data and clinical
      courses. Of 14 fetuses diagnosed, 13 had left sided CDH and one right sided case,
      from 11 to 38 weeks of pregnancy, 10 cases survived. The L/T in 14 fetuses with
      CDH was from 0.08 to 0.36 (mean 0.2 +/- 0.073) and was significantly lower than
      that of the controls. L/T was correlated best with data of arterial pH, PCO2,
      preductal A-aDO2 before operation and the duration of mechanical ventilation in
      survivors. Although L/T was also significantly low in the cases with severe
      grade, diaphragmatic patch closure and ECMO therapy, no significant differences
      were noted in L/T between survivors and non-survivors. These results indicated
      that L/T may predict the severity of lung hypoplasia in CDH and that the
      combination of perinatal management bases on prenatal diagnosis of CDH and ECMO
      support may improve the outcome of fatal CDH with severe lung hypoplasia.

PMID- 1396272
TI  - Transvaginal ultrasound in the first trimester of pregnancy.
AB  - Recent improvements in transvaginal ultrasound permit the extremely detailed
      observation of the morphology of the early conceptus in utero. It is possible to
      use the term "sonoembryology" for the delineation and observation of features
      such as brain vesicles and the neural tube as early as at the beginning of the
      7th week of gestation. In this paper, sonoembryology from 4 to 11 weeks of
      gestation is briefly described.

PMID- 1396274
TI  - A study on the development of sleep-wakefulness cycle in the human fetus.
AB  - We observed fetal behavior by using three ultrasonic real-time scanners
      simultaneously in 30 normal pregnant women between 20 and 40 weeks of gestation
      and analyzed developmental changes in behavioral pattern focussing the attention
      on the characteristics of REM and non-REM sleep and wakeful state. The frequency
      of REM significantly increased with gestational age, and its occurrences formed a
      group in late pregnancy. REM and non-REM periods, which were defined as the phase
      with uninterrupted appearance of rapid eye movements and the phase without them
      over 3 min, respectively, became clearly distinguishable between 28 and 31 weeks
      of gestation. The correlation between the occurrence of rapid eye movements and
      breathing movements was high after 27 weeks. These results demonstrate the course
      of the development of sleep-wakefulness cycle in the human fetus.

PMID- 1396273
TI  - Transvaginal color Doppler assessment of uteroplacental circulation in normal and
      abnormal early pregnancy.
AB  - Transvaginal color Doppler offers the potential to study uteroplacental
      circulation in early normal pregnancies and pregnancies associated with
      intrautine fibroids. A total of 62 patients (30 early pregnancies complicated by
      myoma and 32 normal pregnancies representing the control group) whose gestational
      age ranged from the 6th to the 14th week were examined. The equipment used was an
      Aloka color Doppler SSD-680 with 5.0 MHz curve-linear transvaginal transducer.
      The main uterine, radial and spiral arteries were identified in all patients.
      Peak systolic velocity and resistance index were measured and automatically
      calculated. Statistical analysis used was Student t-test. This study documents a
      physiological decrease in impedance in the uteroplacental circulation in
      pregnancy associated with fibroids, while the blood velocity of the radial
      arteries showed a significant increase between the 10th and 14th week of
      gestation.

PMID- 1396275
TI  - Ethical considerations in safe motherhood (SM) programs in developing countries.
AB  - There are still many maternal deaths in the world each year and over 98% are in
      developing countries. A program of safe motherhood is needed to make certain that
      every woman has the right of basic maternity care.

PMID- 1396276
TI  - Ethical problems in neonatal intensive care unit--medical decision making on the
      neonate with poor prognosis.
AB  - In current NICU (neonatal intensive care units), it is inevitable that ethical
      decisions on neonates with a poor prognosis will have to be made. At Tokyo
      Women's Medical College, we have been applying our own policy of medical decision
      making, which is somewhat different to those of most western countries. Most
      families are not asked to make final decisions, and the ethical committee is not
      actively involved. Staff in the NICU make the decision after plenary discussions.
      The position after decision making is not to discontinue the life supporting
      system but to observe, with no additional treatments and with routine care (class
      C). From October 1984 to September 1989, 58 out of 1589 neonates admitted to the
      NICU at Tokyo Women's Medical College died and 32 (55%) of them were classified
      as class C. The main causes of medical decision making were; non-viable (4/4,
      100%), lethal malformations (13/20, 65%) and birth asphyxia (15/19, 79%).

PMID- 1396277
TI  - A 50-year overview of perinatal medicine.
AB  - Infant mortality in 1990 was approximately one-tenth that of 1950 in most of the
      industrialized countries of the world. The forces of change included the social
      political climate, advent of neonatal intensive care, better insight into
      nutritional requirements of preterm infants and application of basic science to
      the study of events around the time of birth, and illnesses of the neonate.
      Attention has been paid to the advantages of human milk for the newborn infant,
      the importance of maternal bonding and involvement of both parents in care of the
      infant. Prenatal diagnosis, with option of abortion, has reduced the prevalence
      of some serious disorders of the fetus.

PMID- 1396279
TI  - Approaching the millennium: perinatal problems and software solutions.
AB  - Strategic planning for rational development of perinatal computing capabilities
      for the year 2000 should be driven by anticipated trends in (1) the health care
      business, (2) computer technology and (3) medicine, as well as (4) the needs of
      perinatal practitioners. In the USA, health care is the fastest growing segment
      of the economy. This will produce increasing attention from hardware and software
      developers, and vendors, and will lead to a proliferation of computing platforms,
      operating systems and specific medical application software. Desktop computers,
      already capable of 20 million instructions per second (MIPS) with massive storage
      capacities, will continue to evolve and fall in price. Increasingly,
      perinatologists will develop software packages to facilitate patient care in
      their own environments. All of these trends will lead to severe fragmentation in
      medical computing. Simultaneously, however, the need for integrated institutional
      computer-based data access for quality assurance and fiscal and operations
      management will increase. Perinatal care will be more regionalized, complex and
      rigorous with new clinical trial- and effectiveness research-based interventions,
      as well as molecular diagnosis and therapy. To practice appropriately, clinicians
      will need to be familiar with computer capabilities. Having been exposed to
      computer-aided instruction (CAI) at the undergraduate and postgraduate levels,
      they will except on-line access to detailed and accurate patient information with
      linkage to laboratory, radiology and other medical databases, as well as to
      reference databases, such as Medlines and the Oxford Database of Perinatal
      Trials. Artificial intelligence (AI) software may support perinatal decision
      making; computerized professional and facility billing will be available.

PMID- 1396278
TI  - Future horizons in perinatal medicine.

PMID- 1396280
TI  - Surfactant in the perinatal period.
AB  - Surfactant is now available for general clinical use in infants with RDS. While
      surfactant is effective, it does not prevent lung disease in many preterm infants
      because of other aspects of lung immaturity. In experimental models,
      corticosteroids alter the fetal lung by improving compliances, increasing lung
      volumes, decreasing pulmonary edema, and altering surfactant-compliance dose
      response curves. These effects are independent of changes in surfactant pools but
      augment the responses of the lungs to surfactant treatment. Optimal outcomes for
      the preterm require the combined use of fetal maturation strategies and postnatal
      surfactant.

PMID- 1396281
TI  - Non-ketotic hyperglycinemia: a life-threatening disorder in the neonate.
AB  - Non-ketotic hyperglycinemia (NKH) is a well-recognized metabolic cause of life
      threatening illness in the neonate. The fundamental defect is in the glycine
      cleavage enzyme (GCE), which consists of four protein components. Our study
      revealed that the majority of NKH patients had a specific defect in P-protein
      (glycine decarboxylase). The primary lesion of NKH in gene level was
      investigated, using cDNA encoding human glycine decarboxylase. A three-base
      deletion; resulting in deletion of Phe756 was found in a Japanese patient with
      NKH. In the majority of NKH patients in Finland, where there is a high incidence
      of NKH, it was found to be due to a common mutation--a point mutation resulting
      in amino acid alternation from Ser564 to Ile564. Prenatal diagnosis is possible
      by determining the activity of GCE and also by DNA analysis. Recent findings
      suggest that the high concentrations of glycine in the brain may contribute to
      the pathophysiology of NKH by overactivating NMDA receptors via an action at the
      associated glycine modulatory site. These provide a possibility that early
      treatment with NMDA receptor antagonist may prevent brain damage in NKH.

PMID- 1396282
TI  - Behavioral and neurochemical sequelae in young rats of antenal hypoxia.
AB  - To test the hypothesis that perinatal hypoxia may have postnatal consequences via
      a vis learning memory, and neurochemical sequelae, we exposed pregnant Sprague
      Dawley rats to 10.5% O2 for 4 h per day (0800-1200 h) or continuously from
      gestional day E15 to E20. On E20 we quantified ornithine decarboxylase activity
      and polyamine concentrations in fetal brain. We also conducted behavioral tests
      from postnatal day P3 to P110. Relatively mild antenatal hypoxia resulted in
      altered learning, memory, and delayed maturation of early developmental
      sensorimotor function. These behavioral changes disappeared at various postnatal
      ages, depending on the function. Perinatal hypoxia also altered the
      pharmacological response to dopaminergic drugs. In addition, antenatal hypoxia
      feminized a male nonreproductive sexual behavior, that of saccharin preference.
      Acute hypoxia also resulted in an increase in the enzyme ornithine decarboxylase
      and polyamines, which may affect brain development.

PMID- 1396283
TI  - Fetal biochemistry in growth retardation.
AB  - A substantial proportion of fetuses with severe early onset growth retardation
      are chromosomally abnormal and in these cases detailed ultrasound scanning will
      often demonstrate the presence of fetal anatomical defects. Chromosomally normal
      SGA fetuses with no biochemical abnormalities are likely to be normal small
      fetuses and seem to develop normally. SGA fetuses with evidence of impaired
      placental perfusion such as altered fetal cardiovascular dynamics and
      disturbances in biochemical, haematological, metabolic and endocrine status are
      at increased of neurodevelopmental delay. Although incomplete, the data collected
      so far suggest the biochemical changes may be caused by reduced placental
      transfer of nutrients (e.g. oxygen, glucose and essential amino-acids) and
      subsequent reduced fetal metabolism leading to high levels of substrates (e.g.
      triglycerides and non-essential amino-acids) and low levels of tissue products
      (e.g. thyroid hormone, insulin, platelets and white cells).

PMID- 1396284
TI  - Metabolic aspects of fetal and neonatal growth.
AB  - This review covers the transplacental transport of amino acids to the fetus and
      the role of placental metabolism and fetal metabolism in the utilization of amino
      acids. Particular attention is paid to the non-essential amino acids and to their
      rates of production within the fetus or placenta. The supply of amino acids is
      compared with their requirements for accretion in protein and for their use as
      metabolic fuels. Recent studies of protein synthesis in relation to gestational
      age are also reviewed.

PMID- 1396285
TI  - The effect of glucose on Doppler flow velocity waveforms and heart rate pattern
      in the human fetus.
AB  - Twenty-four healthy pregnant women were studied between 36 and 40 weeks gestation
      to determine the effect of glucose on the Doppler flow velocity waveform in the
      cerebral and umbilical arteries of the human fetus near term. The Resistance
      Index (RI), as an index of vascular resistance, was calculated for the anterior
      cerebral, internal carotid and umbilical arteries during a fasting control
      period, 45 min and again at 120 min after a 50-g maternal oral glucose drink or
      an equivalent amount of water. Fetal heart rate (FHR) pattern as determined by
      FHR variability was monitored as a measure of behavioural state. The RI of both
      cerebral vessels was significantly lower after the glucose drink, while that of
      the umbilical artery was little changed subsequent to either of the drinks.
      However the FHR mean min range, as an index of long term FHR variability was
      significantly increased when measured 30 to 60 min after the glucose drink and
      controlling for this change removed the effect of glucose on the RI of the
      cerebral vessels. We conclude that glucose does have an indirect effect on the
      cerebral Doppler waveform indices of the human fetus which is mediated through
      induced changes in behavioural state.

PMID- 1396286
TI  - The temporal relationship between the onset of rapid eye movement period and the
      first micturition thereafter in the human fetus with advance in gestation.
AB  - The objective of this study was to investigate whether micturition occurs,
      temporally related to the onset of the rapid eye movement (REM) period, in the
      human fetus. The study was made on 139 fetuses at 33-36 weeks and 153 at 37-41
      weeks gestation. The discrepancies between the expected (F(exp)) and observed
      (F(obs)) frequencies of time lag between the onset of the REM period and the
      first micturition thereafter were assessed using the goodness-of-fit test. At 33
      36 weeks gestation, there was no statistical difference between F(obs) and F(exp)
      (P greater than 0.05). At 37 weeks onwards, however, significant differences were
      noted between F(obs) and F(exp) (P less than 0.005). Seventy-two percent of all
      micturitions occurred within eight minutes after the onset of the REM period.
      This indicates that there is a temporal relationship between the onset of the REM
      period and the first micturition thereafter, at term, during 37-41 weeks of
      gestation.

PMID- 1396287
TI  - Two different low birth weight formulae compared.
AB  - The performance of two different, commercially available, low birth weight
      formulae feeds was compared in preterm infants. The aim of the study was to
      determine the effect of compositional differences on tolerance, stool frequency
      and consistency, fat balance and weight gain. Inborn infants with birth weight
      less than 1500 g were randomised at birth to receive Prematil or Osterprem.
      Thirty infants received more than 900 ml/kg per week of designated formula alone
      during a total of 70 weeks of study. Three day fat balance was performed on 23
      infants. Osterprem contains 40% more fat than Prematil. The composition of this
      fat is different in that Osterprem contains no medium chain triglycerides (MCT)
      compared to 30% in Prematil. Clinical evaluation demonstrated that Osterprem is
      associated with a significantly higher mean energy intake compared to Prematil
      (3442 and 3127 kJ/kg per week) but mean weight gain is not significantly
      different (123 and 112 g/kg per week). Mean stool frequency is higher on
      Osterprem (20.5 and 14.5 stool/week) and the consistency of stools firmer. This
      is attributable to a higher mean fat output (2.3 and 0.9 g/kg per day) secondary
      to the higher fat content of the feed and lower mean absorption (71.6 and 83.5%).
      Both feeds are well tolerated. The study also confirms that absorption of
      unsaturated fatty acids is inversely proportional to chain length.

PMID- 1396288
TI  - Fetal Doppler velocimetry in the internal carotid and umbilical artery during
      Braxton Hicks' contractions.
AB  - Using Doppler ultrasound, previous studies revealed a considerable increase in
      vascular resistance in the uteroplacental circulation during Braxton Hicks'
      contractions. Consequently, uteroplacental blood flow is reduced and this affects
      placental oxygen transfer to the fetus, causing a fall in fetal arterial PO2. In
      view of the important role of arterial PO2 in the regulation of cerebral blood
      flow in the fetus, we hypothesised that Braxton Hicks' contractions cause a
      decrease in cerebral vascular resistance. A study was undertaken in 16 healthy
      near term pregnancies, using pulsed-wave Doppler ultrasound to evaluate the
      influence of Braxton Hicks' contractions on cerebral vascular resistance of the
      fetus. Flow velocity waveforms (FVWs) were recorded of the fetal internal carotid
      and umbilical artery and the Pulsatility Index (PI) was calculated. During
      Braxton Hicks' contractions the PI in the recorded vessels did not change. Fetal
      heart rate showed also no changes during Braxton Hicks' contractions. These
      findings indicate that resistance to blood flow downstream of these arteries, is
      not significantly altered, suggesting that Braxton Hicks' contractions have
      little or no effect on fetal haemodynamics and on fetal oxygenation in the
      healthy near term fetus.

PMID- 1396289
TI  - Cerebral blood flow fluctuation in low-risk preterm newborns.
AB  - Cerebral blood flow (CBF) fluctuation was studied by analyzing Doppler internal
      carotid blood velocity recordings of 13 healthy preterm newborns obtained in the
      course of their first 5 days of life. As measures of fluctuation we used the
      interquartile range (IQR) and the coefficient of variation (CV) of the ensemble
      of heart beats of a 20-s recording. In this way we determined fluctuation of the
      following velocity curve parameters (VCPs): end diastolic velocity; mean
      velocity; peak systolic velocity and pulsatility index (PI). The pooled data 5
      95% intervals for fluctuation thus measured, were: 93-281% for CV; 0.6-3.7 cm/s
      for the IQR of the velocities; and 4-19% for the PI-IQR. Multiple regression
      analysis of IQR revealed significant relationships with: the VCP level; with
      restlessness; and with patency of the ductus arteriosus. Our findings imply that:
      (1) CBF has various qualities with different stability, mean velocity being the
      most stable; (2) for all the VCPs investigated, fluctuation is physiological in
      the early days after preterm birth; (3) most likely, there exists no age trend;
      (4) restlessness rather than wakefulness, enhances fluctuation; (5) patent ductus
      arteriosus destabilizes CBF; and (6) for a proper insight into fluctuation, the
      level of the VCP in question must be taken into account. We suggest that, the
      enhancing effect that patent ductus arteriosus has on fluctuation pays a
      contribution to the pathogenesis of brain damage. Finally, we conclude that the
      IQR represents fluctuation better than does the more commonly used CV.

PMID- 1396290
TI  - Maternal smoking and tooth formation in the foetus. I. Tooth crown size in the
      deciduous dentition.
AB  - Altogether 2159 pregnancies among black and white Americans in the Collaborative
      Perinatal Study and dental casts from the children at the age of 5-12 years were
      studied to find out the effect of maternal smoking on deciduous tooth crown
      growth. Minor crown size reduction (2-3%) in some dimensions was found in
      children whose mothers had smoked during pregnancy. The possible change in
      dimensions seems to be influenced by sex, race and smoking habit. The critical
      time periods of the gestational development (16th to 19th) weeks would possibly
      appear from these data to be targeted by the detrimental effect of maternal
      smoking. It is concluded that deciduous tooth sizes seem to be greatly unaffected
      when compared to reduction in birthweight.

PMID- 1396291
TI  - Development of the brainstem auditory pathway in low birthweight and perinatally
      asphyxiated children with neurological sequelae.
AB  - Low birthweight (LBW) and perinatal asphyxia are known to be high-risk factors
      for a number of neurodevelopmental deficits. In this study, we analyzed brainstem
      auditory evoked response (BAER) in 18 LBW and 36 perinatally asphyxiated children
      with non-progressive neurological sequelae after the age of 6 months to inspect
      and compare the long-term influence of LBW and perinatal asphyxia on the
      brainstem auditory pathway. The typical changes in the BAER of children born with
      LBW were slightly shorter III-V interpeak interval and smaller III-V/I-III
      interval ratio than normal controls. On the contrary, the abnormalities in the
      BAER of 36 children surviving perinatal asphyxia were characterized by a
      reduction of the amplitude of wave V with normal intervals. This discrepancy in
      the BAER between the children born with LBW and those with perinatal asphyxia
      implies that the two high-risk factors exert different long-term influences on
      the development of the brainstem auditory pathway. It is hypothesized that these
      characteristic changes may be indicative of a major influence of LBW on the
      generators contributing to wave III and that of asphyxia on the generators
      contributing to wave V. An increase in response threshold with abnormal latency
      intensity function was found in 11% of the LBW children and 19% of the
      asphyxiated children, suggesting that sensorineural hearing impairment occurred
      more frequently in children surviving perinatal asphyxia than in those born with
      LBW. Follow-up study demonstrates that the abnormalities in the brainstem
      auditory pathway of LBW and asphyxiated children after the age of 6 months is
      likely to be persistent.

PMID- 1396292
TI  - Ultrasonic dating of pregnancies: effect on incidence of SGA diagnoses. A
      randomised controlled trial.
AB  - In order to study the incidence of antenatal identification and postnatal
      diagnosis of small for gestational age (SGA) infants, 4997 women with optimal
      menstrual history were randomised. One group had the gestational age estimated
      from last menstrual period (LMP), the other from ultrasonographically measured
      biparietal diameter (BPD) in the second trimester. Both the incidence of
      antenatally suspected and postnatally diagnosed SGA infants were reduced by
      approximately 30% in the BPD-dated group. It is concluded that this was due to
      the shift in gestational age estimation.

PMID- 1396293
TI  - Chronic arsenic poisoning masquerading as Landry-Guillain-Barre syndrome.
AB  - Acute arsenic intoxication may present as Landry-Guillain-Barre syndrome because
      of similarities in clinical symptoms involving the gastrointestinal tract,
      weakness, and sensory symptoms. Electrodiagnostic findings may be similar with
      demyelinating changes predominating early in both diseases. A case is presented
      of repeated arsenic poisoning over two years misdiagnosed as Landry-Guillain
      Barre syndrome. Proximal F-loop latency (M-wave latency at wrist + F-wave latency
      at wrist - 2 M-wave latency at axilla) helped to establish the correct diagnosis.
      Serial electrodiagnostic studies were done documenting the evolution of chronic
      repeated arsenic poisoning from a picture showing demyelination to one with
      severe axonal loss.

PMID- 1396294
TI  - Ephaptic influence of the electrical activity of muscle on the neighboring nerve.
AB  - Experiments were performed on isolated nerve-muscle and leg preparations of frog
      in order to investigate the excitatory influence of the electrical activity of
      muscle on the contiguous nerve under various conditions. The results show that
      the active muscles are able to induce multiple transmission of excitation from
      muscle to nerve and to modify the excitation travelling in the nerve being in
      contact with the muscle. It is concluded that under some special circumstances
      the ephaptic influence of the electrical activity of muscle on the nerve in its
      neighborhood can play an occasional role in the processes related with the nerve
      and muscle excitation.

PMID- 1396295
TI  - Electrically elicited short and long-latency responses of intrinsic hand muscles
      in hereditary ataxias. Effects of isometric and ballistic isotonic voluntary
      contractions.
AB  - Short- and long-latency responses (HR and LLR) from thenar muscles were studied
      in patients with Friedreich's ataxia and pure cerebellar ataxia with later onset
      by applying electrical stimuli on the median nerve at the wrist. HR and LLR were
      examined during two different voluntary activities of the opponens pollicis
      muscle: isometric ("hold") and isotonic ballistic ("move") conditions. A
      preliminary conventional study of motor and sensory conduction of the median
      nerve was also carried out. Patients with Friedreich's ataxia had reduced or
      absent HR and LLR. Furthermore, those who preserved both responses had prolonged
      HR-LLR interpeak latency. All patients with Friedreich's ataxia also showed
      peripheral nerve conduction abnormalities, mainly in sensory fibers. These data
      can be accounted for by the widespread degeneration of many neural structures in
      this disorder. No abnormalities in HR were observed in pure cerebellar ataxia
      with later onset, whereas LLR was grossly enlarged in most patients, notably
      during "move" condition. Since cerebellar structures (especially the cerebellar
      cortex) are the only ones involved in this disorder, the cerebellum may play a
      role in modulating LLR. In particular, this effect could be more evident in
      isotonic ballistic movements.

PMID- 1396296
TI  - Myokymic discharges: prompt cessation following nerve root decompression during
      spine surgery.
AB  - In surgical cases during which spine nerve roots are at risk, we have found it
      useful to monitor EMG from the muscles supplied by those roots. Mechanical
      irritation of a root results in muscle activity, whose amplified signals can be
      broadcast over a loudspeaker, providing immediate feedback to the surgeon that
      the root is being irritated. We report here on a patient undergoing spinal canal
      decompression and fusion following a burst fracture of the L5 vertebral body
      sustained five days previously. EMG was continuously monitored from the tibialis
      anterior (TA) and medial gastrocnemius (MG) muscle groups bilaterally. During the
      period leading up to decompression, myokymic discharges from the left TA muscle
      were observed, whereas the other 3 muscles monitored did not show such activity.
      These semi-rhythmic and repetitive discharges from the left TA ceased immediately
      following surgical removal of a bone fragment compressing the left L5 nerve root.
      This indicates that the site of axonal irritation was the nerve root, and that
      myokymic discharges secondary to acute axonal compression can cease immediately
      upon nerve root decompression.

PMID- 1396297
TI  - Increased F-wave duration in patients with spasticity.
AB  - F-wave responses of the posterior tibial nerve have been studied in 22 patients
      with spasticity and in 18 normal control subjects with surface EMG. Mean
      amplitude and mean duration of the F-waves were significantly (p less than 0.001)
      longer in patients with spasticity than in healthy controls. These findings could
      be the result of an enhanced spinal excitability in spasticity. Based on the
      present results F-wave recording may be used as a simple and practical technique
      for detection and documentation of spasticity.

PMID- 1396298
TI  - Clinical application of spinal root neurograms for detection of conduction block
      in radiculopathy.
AB  - In order to assess effects on conductivity of the spinal nerve roots which were
      compressed due to lumbar disc herniation (LDH) and spinal canal stenosis (SCS) at
      the lumbosacral vertebrae, spinal nerve root potentials (SRP) were recorded
      epidurally at multiple levels upon stimulation of the tibial and peronea nerves.
      Subjects were five normal volunteers and fifteen clinical cases (10 LDH and 5
      SCS). Simultaneous recording of evoked EMGs was used to identify afferent and
      efferent components of SRPs. The shortest latency SRP consisted of orthodromic
      group I afferent and antidromic alpha-efferent potentials. The potential on
      liminal M-wave stimulation was regarded as representing exclusively group I
      volley and that on maximal M-wave stimulation as predominantly alpha-efferents. A
      centrifugally conducting nerve potential for H-reflex could be also recorded.
      Conduction blockage in the lumbar spinal roots of the clinical cases could be
      recognized as increased positivity and desynchronization. Quantitative assessment
      of these signs was devised in comparison to the control data. The present method
      revealed at least one of these signs in all clinical cases, and was found useful
      to determine the levels at which surgical decompression is indicated,
      supplementing radiological examination.

PMID- 1396299
TI  - Computer-aided EMG-analysis in patients with neurogenic lesions.
AB  - A new system for computer aided EMG-analysis was tested in 3 groups of patients
      with neurogenic lesions (ALS, ulnar nerve lesions, diabetic polyneuropathy). The
      system entails automatic segmentation and parametrization of the single MUAP as
      well as the automatic classification of the MUAP into motor units. Emphasis was
      placed on its practicability in an everyday clinical setting. All patient groups
      differed significantly from normal groups in most of the computed parameters of
      the motor units. Moreover, on the basis of the computer-aided analysis of the
      MUAP up to 90% of individual patients in the ALS and ulnar nerve lesion groups
      and up to 40% in the diabetic polyneuropathy group, who did not have any
      pathological spontaneous activity or paris, could be classified as pathological.
      It is concluded, that computer-aided EMG-analysis has become a practical tool for
      routine use in the clinical laboratory simplifying early diagnosis of subtle EMG
      changes, and aiding the less experienced examiner.

PMID- 1396300
TI  - Exteroceptive suppression of the trapezius muscle produced by mental nerve
      stimulation in normal subjects.
AB  - The purpose of the present study was to evaluate the similarities and differences
      in exteroceptive suppression produced by mental nerve stimulation between the
      masseter and trapezius muscles. Six normal subjects were studied using various
      intensities of stimulation. Although the duration and degree of exteroceptive
      suppression were increased with stimulus intensity in the masseter muscle, they
      did not correlate with stimulus intensity in the trapezius muscle. The latency
      and duration in the trapezius muscle were almost the same as those in the
      masseter muscle. The degrees in the masseter muscle were significantly larger
      than those in the trapezius muscle. Exteroceptive suppression of the trapezius
      muscle might have a similar mechanism as that of the masseter muscle, but it may
      be mediated by the separate interneurons. The projection from the trigeminal
      afferent to the trapezius motoneuron might be smaller than that to the masseter
      motoneuron.

PMID- 1396301
TI  - Proliferative retinopathy: value of the oscillatory potentials.
AB  - Oscillatory potentials (OPs) and retinal fluorescein angiography (RFA) were
      performed in 45 patients with diabetes mellitus. OPs were normal in 28 patients,
      altered (increased latencies and or inter-peak times) but with normal shape in 9,
      changes in morphology in 8: none of these patients had normal RFA, 2 had no
      proliferative retinopathy, 6 proliferative retinopathy (PR). In the authors'
      opinion OP changes in morphology are nearly always caused by a serious diabetic
      retinopathy, often by a PR. The authors emphasize the usefulness of OPs for
      studying the neurophysiologic properties of the retina of diabetic patients,
      particularly in PR.

PMID- 1396302
TI  - Remembrance: the story of inhibin--the Melbourne version.

PMID- 1396303
TI  - Remembrance: excerpta memorabilia.

PMID- 1396304
TI  - Effects of angiotensin converting enzyme inhibition, sodium depletion, calcium,
      isoproterenol, and angiotensin II on renin secretion by individual renocortical
      cells.
AB  - Angiotensin-converting enzyme inhibition with enalapril increases the number of
      glomeruli with juxtaglomerular cells and the number of cells in the afferent
      arteriole that express the renin gene and contain renin. However, renin release
      from these newly recruited renin-containing cells has not been demonstrated.
      Sodium depletion also has been shown to increase renal renin messenger RNA
      levels. The aim of these studies was to determine whether increases in renin
      secretion are a result of altered numbers of cells synthesizing/releasing renin
      or a change in the amount of renin release per cell, or both. Adult Wistar-Kyoto
      rats were treated with enalapril or sodium depleted and single cell renin
      secretion of enzymatically dispersed renal cortical cells was examined by reverse
      hemolytic plaque assay. Enalapril treatment increased the number of renin
      secreting cells by approximately 10-fold (P < 0.05). The newly recruited renin
      secreting cells were not responsive to changes in extracellular calcium
      concentration or the presence of isoproterenol. At physiological (2.5 mM)
      extracellular calcium concentration, the amount of renin secreted per cell was
      approximately 2-fold greater (P < 0.05) when cells from enalapril-treated rats
      were compared to controls and sodium depletion increased both the number of renin
      secreting cells and the amount of renin secreted by approximately 35% (P < 0.05).
      Angiotensin II (AII) inhibited the number of cells secreting renin in cortical
      cells prepared from enalapril-treated and control rats. In conclusion,
      angiotensin converting enzyme inhibition increased renin secretion predominantly
      by recruitment of additional renin-secreting cells and, to a lesser extent, by
      augmentation of the amount of renin released per cell. In contrast, sodium
      depletion increased renin secretion equally by both mechanisms. Newly recruited
      renin-secreting cells were not regulated by the extracellular calcium
      concentration or beta-adrenergic stimulation. Angiotensin II inhibited renin
      secretion directly by decreasing the number of individual cells releasing renin
      through a process which was independent of the extracellular calcium
      concentration.

PMID- 1396305
TI  - Production of mouse placental lactogen-I and placental lactogen-II by the same
      giant cell.
AB  - In previous studies, mouse placental lactogen I (mPL-I) and mPL-II were localized
      to trophoblast giant cells in the placenta at midpregnancy. The present study was
      undertaken to determine whether mPL-I and mPL-II are produced by two distinct
      populations of giant cells or by the same cells. A heterogeneous population of
      cells that included trophoblast giant cells was obtained by enzymatic dispersion
      and Percoll gradient centrifugation of placentas from days 7 and 9 of pregnancy.
      Cells from day 7 of pregnancy were cultured in serum-free medium for 5 days, and
      cells that contained mPL-I, mPL-II, or both mPL-I and mPL-II were identified by
      double-staining immunocytochemistry. The percentage of PL cells that contained
      both mPL-I and mPL-II increased from about 30% on the first day of culture to
      about 90% on the third, and then declined to zero by day 5. Between 50% and 60%
      of the PL cells contained only mPL-I on the first 2 days of culture, and then the
      percentage of PL cells containing only mPL-I declined. The percentage of cells
      that contained only mPL-II was low for 3 days (<10%) and then increased to about
      80% of the PL-containing cells by day 5. Cells from day 9 of pregnancy were
      analyzed for the release of mPL-I and/or mPL-II by sequential reverse hemolytic
      plaque assay. Cells that released only one of the PLs, as well as those that
      released both PLs, were identified. A shift was present in the type of PL
      released by the cells when they were followed for two consecutive days of
      culture. On day 1, most of the plaque-forming cells released only mPL-I, but by
      day 2, the fraction of plaque-forming cells that released only mPL-I declined
      whereas the fraction that released only mPL-II increased. Cells that released
      only mPL-I on the first day of culture and both mPL-I and mPL-II or only mPL-II
      on the second day of culture were observed. These data suggest that under these
      culture conditions, PL cells follow a pathway in which they initially produce
      only mPL-I, then both mPL-I and mPL-II, and finally only mPL-II. In vivo, there
      is a shift at midpregnancy in the type of PL that is produced by the mouse
      placenta, and these data suggest that this shift results, at least partly, from a
      change in gene expression in one population of giant cells.

PMID- 1396306
TI  - Effect of restricted feeding, fasting, and diabetes on the relationship between
      thyroid hormone receptor occupancy, growth hormone induction, and inhibition of
      thyrotropin release in thyroidectomized rats.
AB  - The present study was undertaken to test the effect of food restriction, fasting,
      and diabetes on the relationship between thyroid hormone receptor occupancy and
      two biological end points, GH production and the inhibition of TSH secretion, in
      thyroidectomized rats. The estimated maximal binding capacity (MBC) in diabetic
      (D) and fasting (F) rats and in animals limited to 25% (FR25) of the food
      consumption of normal (C) rats was decreased to 57%, 73%, and 76%, respectively,
      of C values (P < 0.01-0.001), whereas normal values were found in
      thyroidectomized (Tx) rats and in animals limited to 50% (FR50) of the food
      intake of C animals. The nuclear T3 content and T3 receptor occupancy were
      reduced, respectively, to 25% and 29% in Tx, 77% and 81% in FR50, 52% and 69% in
      FR25, 49% and 66% in F, and 36% and 64% in D rats of the corresponding C values
      (P < 0.05-0.001). Pituitaries from Tx, FR50, FR25, F, and D rats contained less
      GH than C pituitaries (0.14%, 81%, 69%, 88%, and 51%, respectively, of C
      pituitaries; P < 0.05-0.001). Plasma TSH was lower in FR50, FR25, F, and D rats
      than in C animals (78%, 57%, 52%, and 48%, respectively (P < 0.01-0.001)), and
      markedly increased in Tx animals. Administration of a single dose of 2, 5, or 10
      micrograms T3/100 g BW to Tx C, Tx FR50, TX FR25, Tx F, and Tx D rats resulted in
      a similar and progressive increase in nuclear T3 in all groups, except for lower
      values in Tx D animals. However, receptor occupancy did not differ among the
      different groups at each T3 dose. This treatment resulted in a progressive
      increase in pituitary GH in all groups; however, in Tx FR50, Tx FR25, Tx F, and
      Tx D pituitaries, the GH responses to 10 micrograms T3 were only 77%, 59%, 44%,
      and 27%, respectively, of that in Tx C rats. (P < 0.05-0.001). Moreover,
      significant differences in the GH response to 10 micrograms T3 were observed
      among Tx FR50, Tx FR25, Tx F, and Tx D animals (P < 0.01-0.001). In addition
      plasma TSH levels in untreated Tx FR50, Tx FR25, Tx F, and Tx D rats were only
      88%, 82%, 79%, and 72%, respectively, of that in Tx C animals (P < 0.05
      0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1396307
TI  - Tissue selective modulation of redox and phosphate potentials by beta,beta'
      methyl-substituted hexadecanedioic acid.
AB  - beta,beta'-Methyl-substituted hexadecanedioic acid (MEDICA 16) shares some of the
      calorigenic-hypolipidemic characteristics of thyroid hormones. In light of this
      similarity, MEDICA 16 was further evaluated here as a modulator of rat liver
      redox and phosphate potentials as well as an effector of cardiac high energy
      intermediates level in comparison to thyroid hormone. 1) Similarly to thyroid
      hormone, MEDICA 16 treatment resulted in 3.5-fold decrease in cytosolic redox
      potential. With both treatment modes, the induced decrease in cytosolic redox
      potential resulted in a concomitant increase in the liver capacity of handling an
      ethanol or xylitol load. 2) The apparent liver cytosolic phosphate potential
      calculated from the glycerol-3-phosphate 3-phosphoglyceric acid ratio evaluated
      under conditions of rapid equilibrium within the glycerol-3 phosphate/3
      phosphoglyceric acid metabolic section was found to remain unaffected by either
      MEDICA 16 or T3 treatment. However, the apparent cellular phosphate potential was
      substantially decreased by both treatment modes, thus reflecting a decrease in
      the apparent liver mitochondrial phosphate potential. 3) Similarly to thyroid
      hormone, the effect of MEDICA 16 on liver redox and phosphate potentials could be
      accounted for by induction of mitochondrial glycerol-3-phosphate dehydrogenase.
      4) In contrast to liver, heart high energy intermediates were affected by thyroid
      hormone but not by MEDICA 16 treatment. 5) The effect of T3 and MEDICA 16 with
      respect to liver redox and phosphate potentials may partially account for the
      calorigenic-hypolipidemic effect of both. MEDICA 16 may however serve as a
      selective liver thyromimetic agent lacking the cardiac affect induced by thyroid
      hormone.

PMID- 1396308
TI  - Expression of insulin-like growth factor-II (IGF-II) and IGF-II/mannose-6
      phosphate receptor in the rat hippocampus: an in situ hybridization and
      immunocytochemical study.
AB  - After 3 or 4 weeks of age, insulin-like growth factor-II (IGF-II) gene expression
      in normal rats has been detected only in mesenchymal tissue associated with the
      central nervous system. In contrast, the IGF-II/mannose-6-phosphate receptor has
      been reported to be widely distributed in adult rat brain. This study was
      performed in order to clarify the cellular localization of IGF-II and IGF
      II/mannose-6-phosphate receptor in rat brain by comparing an immunocytochemical
      map with the distribution of mRNAs by in situ hybridization. The highest levels
      of IGF-II mRNA were detected in the choroid plexus and meningeal membranes. In
      contrast, IGF-II receptor transcripts were mainly present in neuron-rich areas
      such as the hippocampus, with a lower signal present in the choroid plexus and
      meninges. Specific IGF-II receptor immunoreactivity was present in neurons
      throughout the forebrain, with the highest intensity in the pyramidal cell and
      polymorphic layers of the hippocampus and the granule cell layer of the dentate
      gyrus. This distribution was similar to that obtained with the in situ
      hybridization technique. No glial staining was detected. Although the role of IGF
      II in the adult rat brain, acting through its specific receptor, is not clear; in
      vitro and in vivo data suggest a possible neurotropic and/or neuromodulatory
      action.

PMID- 1396309
TI  - Interleukin-1 is both morphogenic and cytotoxic to cultured rat ovarian cells:
      obligatory role for heterologous, contact-independent cell-cell interaction.
AB  - An increasing body of information now suggests that intraovarian interleukin-1
      (IL-1) may play an intermediary role in the ovulatory process. Given that
      follicular rupture inevitably requires marked tissue remodeling and possibly cell
      death, we set out to examine the morphogenic potential of IL-1 under in vitro
      circumstances. Treatment of freshly plated whole ovarian dispersates from
      immature rats with any one of several batches of IL-1 (10 ng/ml) for up to 96 h
      produced marked time-dependent morphological alterations, including cellular
      retraction, rounding, clumping, aggregation, blebbing, swelling, and, ultimately,
      irreversible detachment. Evidence of (asynchronous) cell death consisted of
      reduced total cell number, diminished cellular protein content, enhanced cellular
      release of lactic dehydrogenase, failure to exclude trypan blue, and attenuated
      reduction of the tetrazolium dye 3-[4,5-dimethylthiazol-2-y]2,5
      diphenyltetrazolium bromide to spectrophotometrically detectable formazan.
      Comparable results were obtained when using established day 4 cultures, arguing
      against a possible critical action of IL-1 at the time of plating. Dose-response
      curves revealed IL-1 beta (EC50, 0.2-0.4 ng/ml) to be substantially more potent
      than IL-1 alpha (EC50, 2.7-2.8 ng/ml). Importantly, the concurrent provision of
      an IL-1 beta-directed polyclonal antibody yielded complete immunoneutralization
      of the IL-1 beta effect, arguing against the possible involvement of a non-IL-1
      contaminant. An unrelated polyclonal antiserum raised against insulin-like growth
      factor-I was without effect. IL-1 action proved relatively specific, in that
      tumor necrosis factor-alpha (10 ng/ml), a putative cytotoxic principle, as well
      as IL-1-inducible ILs (IL-2 and -6; 100 U/ml) were without effect. Although
      minimally effective at the level of the isolated granulosa or theca-interstitial
      cell, IL-1 proved highly potent in heterologous (but not homologous), contact
      dependent and independent cocultures of these somatic cell types, strongly
      suggesting obligatory cell-cell cooperation. These observations further indicate
      that IL-1 action is indirect and may require the induction of an intermediary
      soluble principle to serve as the final effector. Taken together, these findings
      indicate that relatively low concentrations of IL-1 (beta >> alpha), possible of
      somatic ovarian cell or resident ovarian macrophage origin, are capable of
      exerting specific dose- and time-dependent (immunoneutralizable) morphogenic as
      well as cytotoxic effects at the level of ovarian cells.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1396310
TI  - Transforming growth factor-alpha is a potential mediator of estrogen action in
      the mouse uterus.
AB  - To better understand the role of peptide growth factors in sex steroid hormone
      mediated growth of the female reproductive tract, the effect of estrogen on the
      expression of transforming growth factor-alpha (TGF alpha) in mouse uterus was
      investigated. Our results show that estrogen induces the expression of TGF alpha
      mRNA in the mouse uterus in a dose- and time-dependent manner. The up-regulation
      of TGF alpha transcripts occurs predominantly in uterine epithelial cells. RIA
      and Western blot analysis demonstrate that immunoreactive TGF alpha protein is
      secreted at high levels into mouse uterine luminal fluid after estrogen
      treatment. The induction of uterine TGF alpha mRNA is specific to estrogen;
      nonestrogenic steroids did not induce expression. Antibody specific to TGF alpha
      significantly reduces estrogen-mediated uterine growth, which supports the
      concept that TGF alpha is a mitogen for the reproductive tract. Analysis of TGF
      alpha/EGF receptors by binding, affinity labeling, and phosphorylation studies
      indicates that functional receptors are present in the mouse uterus after
      estrogen exposure. Thus, our data support a physiological role for TGF alpha and
      its receptor pathway in the female mouse reproductive tract.

PMID- 1396311
TI  - Photoperiodic modulation of luteinizing hormone secretion in orchidectomized
      Syrian hamsters and the influence of excitatory amino acids.
AB  - The effect of N-methyl-D,L-aspartate (NMA) on LH secretion was investigated in
      Syrian hamsters of the LSH/Ss Lak strain, maintained under either long days (14 h
      of light, 10 h of darkness) or short days (6 h of light, 18 h of darkness). After
      6 weeks of photoperiodic treatment, the animals were orchidectomized. Ten days
      later, 10-min blood samples were remotely collected from each animal, using
      surgically implanted intraatrial catheters, and individual pulsatile LH release
      profiles were subsequently determined by RIA. At the end of the 4-h sampling
      period, NMA was administered iv (30 mg/kg BW), and the LH response was determined
      in the next three plasma samples. Hamsters maintained under long days had very
      high mean plasma LH levels (453 +/- 46 ng/ml) and displayed episodic release
      patterns characterized by high amplitude pulses. In marked contrast, hamsters
      that were maintained under short days had significantly (P less than 0.001) lower
      mean plasma LH levels (90 +/- 12 ng/ml) and showed a significantly (P less than
      0.001) lower mean pulse amplitude. The interpulse interval was similar in both of
      the groups, with LH peaks occurring, on the average, once every 65 min. When
      challenged with NMA, the long-day hamsters showed only a 37% increase in mean
      plasma LH levels, which was not statistically significant. In contrast, the short
      day hamsters showed a highly significant (P less than 0.01) increase of 294%.
      Interestingly, the mean plasma LH levels after NMA administration were the same
      in the two photoperiodic groups despite a marked difference in the plasma levels
      that preceded the administration. These findings demonstrate that short days can
      inhibit the neuroendocrine activity of the hamster's reproductive axis
      independently of gonadal influences. They also suggest that the LHRH neurons have
      an intrinsic capacity to secrete very high levels of the neuropeptide, regardless
      of the photoperiod. Taken together, the results support the hypothesis that the
      breeding season in the hamster is regulated by a gonad-independent mechanism
      involving a photoperiodic modulation of neuroexcitatory inputs to the LHRH
      neurons.

PMID- 1396312
TI  - Apoptosis in atretic ovarian follicles is associated with selective decreases in
      messenger ribonucleic acid transcripts for gonadotropin receptors and cytochrome
      P450 aromatase.
AB  - Although atresia of ovarian follicles is of critical importance during
      preovulatory follicle selection as well as during normal and premature menopause,
      the mechanisms underlying atresia remain poorly understood. To study molecular
      events associated with atresia, we evaluated changes in mRNA levels for
      cytochrome P450 aromatase, FSH receptor, LH receptor, and a structural protein,
      beta-actin, during atresia in small (3-mm diameter) and large (6-mm diameter)
      porcine follicles. In addition, internucleosomal fragmentation of DNA
      characteristic of apoptosis ("programmed cell death") was assessed in individual
      healthy and atretic follicles using a sensitive autoradiographic method.
      Follicles were classified as morphologically healthy or atretic based on the
      absence or presence of follicular haemorrhagia and the degree of follicular
      clarity. Morphological signs of atresia in individual follicles were correlated
      with the occurrence of internucleosomal DNA fragmentation in granulosa cells as
      well as in thecal cells during advanced stages of atresia. The presence of
      apoptosis in atretic follicles was also associated with significant decreases in
      follicular fluid estrogen concentrations compared to those in healthy follicles
      of the same size. The decline in estrogen synthesis in degenerating follicles was
      further correlated with decreased levels of a predominant 2.6-kilobase aromatase
      mRNA. Moreover, substantial declines in both FSH receptor and LH receptor mRNAs
      were found in atretic follicles, consistent with previous reports of their
      decreased responsiveness to gonadotropins. The observed decreases in mRNAs for
      aromatase and gonadotropin receptors could not be attributed to a generalized
      degradation of cellular RNA during atresia, as evidenced by the presence of
      intact 18S and 28S ribosomal RNA as well as constitutive expression of beta-actin
      mRNA in atretic follicles. These data indicate that apoptotic cell death is
      initiated in both granulosa and thecal cells of porcine follicles during atresia.
      Associated with internucleosomal DNA fragmentation, decreased transcription of
      specific ovarian genes or destabilization of their transcripts leads to selective
      decreases in aromatase and gonadotropin receptor mRNAs. The atresia of ovarian
      follicles provides an interesting model to further study the molecular events
      associated with DNA fragmentation and selective mRNA down-regulation during
      apoptosis.

PMID- 1396313
TI  - Pretreatment with 1,25-dihydroxycholecalciferol enhances thyrotropin-releasing
      hormone- and inositol 1,4,5-trisphosphate-induced release of sequestered Ca2+ in
      permeabilized GH4C1 pituitary cells.
AB  - In GH4C1 cells 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] has been shown to
      enhance the TRH- and bombesin-induced increase in intracellular Ca2+ ([Ca2+]i).
      The aim of the present study was to investigate whether this increase in [Ca2+]i
      could be due to enhanced release of sequestered Ca2+ in cells pretreated with
      1,25-(OH)2D3. In digitonin-permeabilized cells, the addition of 10 microM
      inositol 1,4,5-trisphosphate (IP3) rapidly increased free Ca2+ ([Ca2+]) to 50 +/-
      10 nM (mean +/- SE) in cells pretreated with 1 nM 1,25-(OH)2D3 for 24 h, compared
      with 25 +/- 5 in control cells (P < 0.05). Furthermore, stimulating permeabilized
      cells with TRH increased [Ca2+]. The increase in control cells was 20 +/- 2,
      compared with 55 +/- 11 in cells pretreated with 1,25-(OH)2D3 (P < 0.05).
      Repeated additions of IP3 resulted in an attenuation of the response of [Ca2+] in
      both control cells and cells pretreated with 1,25-(OH)2D3. However, only the
      first addition of IP3 resulted in an enhanced increase in [Ca2+] in cells
      pretreated with 1,25-(OH)2D3 compared with control cells. If the cells were
      stimulated first with TRH and then with IP3, no difference in the [Ca2+] response
      was observed between control cells and cells pretreated with 1,25-(OH)2D3.
      Furthermore, if cells were stimulated with IP3 and then with TRH, no difference
      in the [Ca2+] response was observed between control cells and cells pretreated
      with 1,25-(OH)2D3. Stimulating the permeabilized cells with thapsigargin resulted
      in an increase in [Ca2+]. However, no difference in the response was observed
      between control cells and cells pretreated with 1,25-(OH)2D3. Addition of GTP or
      the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) had no effect
      on [Ca2+]. The results suggest that 1,25-(OH)2D3 has a modulatory effect on an
      IP3-sensitive intracellular Ca2+ pool in GH4C1 cells.

PMID- 1396314
TI  - Induction of type III deiodinase activity in astroglial cells by thyroid
      hormones.
AB  - The type III deiodinase (D-III) activity in astroglial cells is induced by
      multiple pathways activated by cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA),
      and fibroblast growth factors (FGFs). This study examines the effects of thyroid
      hormones on D-III activity in astroglial cells with or without induction by these
      factors. Addition of 10 nM T3 to the culture medium caused a slow increase in D
      III activity, which reached a plateau after 48 h. This increase was concentration
      dependent (maximal response at 10 nM). Doses as low as 0.3 nM caused significant
      increases in D-III activity. The effect of T3 was reversible. A dose of 10 nM L
      T3, D-T3, T4, 3,5,3'-triiodothyroacetic, or 3'-isopropyl-3,5-diiodothyronine
      produced 5- to 15-fold increases in D-III activity after 48 h. In contrast, 10 nM
      L-thyronine, 3-monoiodothyronine, 3,3'-diiodothyronine, 3,5-diiodothyronine, and
      rT3 were without effect. A dose of 10 nM T3 or T4 amplified the D-III activity
      stimulated by 0.1 microM TPA, 20 ng/ml acidic FGF, or 1 mM 8-bromo-cAMP 3- to 8
      fold. Otherwise, T3 rapidly inhibited D-II activity. This inhibition was
      concentration dependent, with a half-maximal effect around 10 nM. In conclusion,
      thyroid hormones induce D-III activity and potentiate the D-III activity induced
      by cAMP, TPA, and FGFs in astroglial cells. These reversible effects together
      with inhibition of D-II activity may contribute to protect the brain against
      hyperthyroidism.

PMID- 1396315
TI  - A study of metabolism of deaminated and sulfoconjugated iodothyronines by rat
      placental iodothyronine 5-monodeiodinase.
AB  - The interaction of the rat placental type III iodothyronine 5-monodeiodinase (5
      MD) with acetic acid (AA), propionic acid (PA), and sulfoconjugate (SA)
      derivatives of thyroid hormones has been investigated in comparison with hepatic
      iodothyronine type I MD. PA and AA derivatives of both T3 and T4 were potent
      inhibitors of 5-monodeiodination of [125I]T3 by rat placental microsomes. 3,5,3'
      Triiodothyroacetic acid (T3AA) and 3,5,3'-triiodothyropropionic acid (T3PA) were
      comparable to T3 in their ability to inhibit 5-monodeiodination of [125I]T3,
      whereas T4AA and T4PA were more potent than T4. 3,5,3'-triiodothyrosulfonic acid
      (T3SA), T4SA, and rT3SA caused little or no inhibition of placental 5-MD
      activity. Among various analogs of T3 or T4, the order of relative potency of
      inhibition of hepatic 5'-MD was PA > AA > SA > parent iodothyronine. The
      metabolism of T3 and its derivatives by rat placental microsomes was studied by
      determining the rates of disappearance of the various substrates and the
      production of the metabolites generated by inner ring monodeiodination of the
      substrate. T3AA and T3PA were metabolized at a rate comparable to that of T3.
      Under the same conditions, essentially 100% of T3SA remained intact. Kinetic
      studies of placental inner ring monodeiodination of T3, T3AA, and T3PA
      demonstrated comparable values for Km (1.3, 1.8, and 2.3 nM, respectively) and
      maximum velocity (44, 57, and 74 fmol/micrograms.h, respectively). All
      derivatives of T3 studied were deiodinated by hepatic type I MD more avidly than
      the parent iodothyronine. Our data suggest that 1) deamination does not
      appreciably influence, while sulfoconjugation markedly inhibits type III 5
      monodeiodination of T3; and 2) deamination may be even more conducive to
      degradation of thyroid hormone than sulfoconjugation.

PMID- 1396316
TI  - In vivo effects of interferon-alpha and interferon-gamma on lipolysis and
      ketogenesis.
AB  - The host response to infection and cancer produces disturbances in fatty acid
      (FA) oxidation and ketogenesis. Interferons (IFNs) stimulate lipolysis in
      cultured adipocytes. Since FA mobilization is a major stimulus for ketogenesis,
      we studied the effect of IFN alpha and IFN gamma on lipolysis and ketogenesis in
      intact mice. Both IFNs acutely stimulated lipolysis; however, their effects on
      ketogenesis differed. INF gamma increased serum and hepatic ketone body levels in
      parallel to its effect on serum FFA, whereas IFN alpha exerted a biphasic effect
      on ketogenesis. At low doses, IFN alpha increased serum and hepatic ketone body
      levels, whereas at higher doses, this ketogenic effect was abolished. To
      determine the mechanism of the biphasic response, we studied the effect of IFN
      alpha on hepatic malonyl-coenzyme-A (malonyl-CoA), the first committed
      intermediate in FA synthesis and an inhibitor of FA oxidation and ketogenesis. At
      low doses, IFN alpha had no effect on malonyl-CoA; however, higher doses of IFN
      alpha significantly increased malonyl-CoA levels, which could counterbalance its
      mobilization of FFA. In contrast, INF gamma had little effect on malonyl-CoA, and
      hence, the FA oxidation was not opposed. By using phenylisopropyladenosine to
      block IFN-induced lipolysis, we found that in the absence of increased FA flux,
      INF gamma did not exert a ketogenic effect. However, when IFN alpha-induced
      lipolysis was blocked, the higher doses of IFN alpha that raise malonyl-CoA
      levels were antiketogenic. These data suggest that both IFNs exert a ketogenic
      effect by stimulating lipolysis, but at higher doses the ketogenic effect of IFN
      alpha is counteracted by its effect on hepatic FA synthesis.

PMID- 1396317
TI  - Central C-type natriuretic peptide but not atrial natriuretic factor lowers blood
      pressure and adrenocortical secretion in normal conscious sheep.
AB  - C-type natriuretic peptide (CNP) and its specific receptor (ANPRB) are richly
      distributed throughout the brain, especially the anterior pituitary and
      hypothalamus but not in tissue of nonneural origin. These findings suggest that
      the actions of CNP, unlike atrial natriuretic factor (ANF), are largely confined
      to the brain where CNP may participate in the central regulation of hemodynamics
      and salt and water balance. Therefore, we have studied the hemodynamic, renal,
      and hormonal effects of continuous intracerebroventricular infusions of CNP (5
      micrograms/h for 4 h) in a vehicle-controlled study and compared the responses to
      those of ANF in normal conscious sheep. Hemodynamic and hormonal responses to ANF
      were not different from control infusions. There was a trend for urinary sodium
      and potassium excretion to increase throughout the control infusion but not on
      the ANF day. Water intake during control infusion (358 +/- 160 ml/4 h) was almost
      3-fold that ingested during ANF (127 +/- 89 ml/4 h, NS). In contrast, CNP induced
      a prompt fall in mean arterial pressure (mean decrement 5 mm Hg), arterial
      pressure remaining below time control values for the remainder of the infusion (P
      = 0.006). Rises in both heart rate and PRA observed on the control day tended to
      be attenuated by CNP. Urine electrolyte response to CNP was similar to that
      observed with ANF. Compared with control infusions, the responses of both plasma
      aldosterone (P = 0.006) and cortisol (P = 0.043) were significantly different.
      Following CNP-induced hypotension, plasma cortisol and aldosterone increased
      abruptly at 30 min after which values fell to control or lower levels until the
      infusion was terminated. These studies show that intracerebroventricular CNP
      lowers arterial pressure without increasing heart rate and also suppresses the
      adrenocortical response, whereas ANF given under the same conditions has no
      significant effects. These data support the hypothesis that CNP plays an
      important role in the central regulation of blood pressure and hormones.

PMID- 1396318
TI  - Impairment of glycosyl-phosphatidylinositol-dependent insulin signaling system in
      isolated rat hepatocytes by streptozotocin-induced diabetes.
AB  - The addition to different types of cells of an inositol-phosphate glycan,
      generated by the phospholipase C-catalyzed hydrolysis of a insulin-sensitive
      glycosyl-phosphatidylinositol (glycosyl-PI), mimics some of the biological
      effects of this hormone. Recently, a specific, time-, dose-, and energy-dependent
      transport system for this inositol-phosphate glycan has been identified in
      isolated rat hepatocytes. Here, we show that streptozotocin-induced diabetes
      mellitus reduced (by about 60%) the basal content of the insulin-sensitive
      glycosyl-PI in isolated rat hepatocytes. Moreover, streptozotocin-induced
      diabetes blocked the hydrolysis of the glycosyl-PI in response to insulin,
      diminished inositol phosphate-glycan uptake by the hepatocytes, and abolished the
      stimulatory effect of this compound on glycogen synthesis. All these metabolic
      changes caused by streptozotocin administration were reversed by treatment of the
      animals with insulin. Our results support the hypothesis that insulin resistance
      in streptozotocin-induced diabetic rats is related to the impairment of glycosyl
      PI metabolism.

PMID- 1396319
TI  - Characterization of the structure and glycosylation properties of intracellular
      and cell surface rat hepatic prolactin receptors.
AB  - In this study we examined the structure of the PRL receptor of rat liver. We used
      immunoblotting with monoclonal antibodies to binding and nonbinding site epitopes
      of the PRL receptor to assess receptor subtypes in different hepatic subcellular
      fractions. Analysis of frozen-thawed cell fractions revealed 40- and 42
      kilodalton (kDa) species. Digestion with neuraminidase indicated that both
      species were terminally sialylated. Freshly isolated membranes exhibited a single
      42-kDa species in all subcellular fractions, whereas freeze-thawing generated the
      40-kDa species. The carbohydrate linkages present in the PRL receptor were
      examined using enzymes to deglycosylate iodinated purified receptors. These
      studies indicated that oligosaccharides comprise about 7 kDa of receptor mass and
      that they are exclusively N-linked, consisting of tri- and/or tetra-antennary
      complex glycans. Monoclonal antibodies to the receptor recognized the
      deglycosylated receptor. Maximally deglycosylated receptors retained about 85% of
      their binding capacity. After in vivo tunicamycin treatment of rats, total PRL
      receptors (as determined by immunoblot analysis and binding activity) disappeared
      with a half-time of about 25 min. In this circumstance, no aglycosylated receptor
      species were recognized by monoclonal antibodies. Since deglycosylation of mature
      receptors did not markedly reduce binding capacity, we infer that mature
      receptors do not accumulate during the blockade of glycosylation by tunicamycin.
      Thus, glycosylation appears to be required for the acquisition of a mature
      receptor status, but is not necessary for the maintenance of that status.

PMID- 1396320
TI  - Thyroxine sulfate is a major thyroid hormone metabolite and a potential
      intermediate in the monodeiodination pathways in fetal sheep.
AB  - T3 and rT3 production rates in the fetus account for roughly only a third of the
      total T4 production rate; thus, the fate of the majority of T4 produced in the
      fetus is unknown (the "T4 disposal gap"). We developed sensitive and specific T4
      sulfate (T4S) and T3 sulfate (T3S) RIAs to investigate the roles of these
      compounds in fetal T4 metabolism. T3, T4, T3S, and T4S were determined in a
      variety of tissue fluid and/or serum samples obtained from fetal, newborn (n =
      6), and adult (n = 6) sheep. Four groups of fetal animals, with gestational ages
      of 94 days (n = 5), 110-111 days (n = 6), 130-131 days (n = 6), and 145 days (n =
      6; term = 150 days), were studied. In addition, type I 5'-monodeiodinase (5'-MDI)
      activity was quantified in liver and kidney tissues. 5'-MDI activities were lower
      in 94- to 131-day-old fetuses than in fetuses near term or in newborn animals.
      Mean serum T3 concentrations increased progressively from 94 days (19 ng/dl) to
      term (371 ng/dl), while mean T3S and T4S serum concentrations were highest at 130
      days gestation (237 and 989 ng/dl), decreasing to term. Serum T3S and T4S
      concentrations decreased further in newborns and adult sheep. T4S and T3S levels
      in allantoic fluid were significantly higher than those in urine and amniotic
      fluid in all fetal age groups studied. T4S levels in bile were high from 94-130
      days gestation (873-1006 ng/dl), decreasing by 50% at term (529 ng/dl). T4S
      concentrations in meconium were 46- to 83-fold higher than those in bile from 94
      days gestation to term. In contrast, bile T3S levels increased progressively from
      94-145 days gestation (191-605 ng/dl), while meconium T3S levels decreased during
      the same period (33-14 micrograms/100 g). These data demonstrate that 1) sulfated
      iodothyronines, particularly T4S, are major thyroid hormone metabolites in the
      fetus; 2) both T4S and T3S are excreted into bile and urine and concentrated in
      meconium and allantoic fluid; and 3) the high levels of T4S and T3S in serum and
      other fluids may reflect lower tissue type I 5'-MDI activities. We speculate that
      T4S and T3S may be further metabolized to other sulfated metabolites and may
      account in part for the T4 disposal gap in fetal sheep.

PMID- 1396321
TI  - Mechanisms of desensitization to parathyroid hormone in human osteoblast-like
      SaOS-2 cells.
AB  - Signal transduction by the PTH receptor is now known to involve generation of
      multiple second messengers. Desensitization of the adenylate cyclase response to
      PTH is a common feature of bone- and kidney-derived target cells; however, no
      single mechanism appears to explain desensitization in the different cell types
      studied. To examine the role of protein kinase-A (PKA) in homologous
      desensitization to PTH, we employed human SaOS-2 osteoblast-like cells and a
      mutant subclone (Ca 4A), which expresses an inducible cAMP-resistant form of PKA.
      Pretreatment of SaOS-2 cells with PTH for 4 h reduced by 60-80% the cAMP response
      to subsequent rechallenge with the hormone. This homologous desensitization was
      significantly, but not completely, inhibited in Ca 4A cells. Desensitization was
      not mimicked by pretreatment of the cells with forskolin. PTH binding to its
      receptor was reduced 50% in both SaOS-2 and Ca 4A cells after 4-h incubation with
      PTH (homologous down-regulation), whereas forskolin did not cause receptor down
      regulation. Pretreatment with the ionophore ionomycin for 4-24 h did not mimic
      desensitization to PTH. Both desensitization to PTH and receptor down-regulation
      were induced, however, by pretreatment with a phorbol ester (12-O-tetradecanoyl
      phorbol-13-acetate), and these effects were blocked completely by staurosporine.
      PTH-induced desensitization was not blocked by staurosporine, and receptor down
      regulation was enhanced by the drug. Pertussis toxin did not prevent
      desensitization induced by either PTH or 12-O-tetradecanoyl phorbol-13-acetate.
      We conclude that homologous desensitization to PTH in SaOS-2 cells involves both
      cAMP-dependent and -independent mechanisms. Homologous PTH receptor down
      regulation apparently is mediated by mechanisms independent of PKA activation.
      Neither pathway of homologous desensitization to PTH involves the action of
      pertussis toxin-sensitive G-proteins.

PMID- 1396322
TI  - The presence of glandular kallikrein in rabbit fetal placental conditioned
      medium.
AB  - Glandular (tissue) kallikreins are known to be involved in the posttranslational
      modification of protein hormones and growth factors in addition to their
      classical role as the bradykinin-releasing enzyme in tissues. They have been
      shown to be present in many tissues, such as the pancreas, salivary glands,
      pituitary, and testes. The objective of this study was to investigate the
      presence of kallikrein in the rabbit placenta. Day 21 pregnant rabbit fetal
      placentae were teased apart in medium 199, washed thoroughly, and incubated in
      fresh medium for 6 h at 37 C. The resulting placental conditioned medium (FPI)
      was found to have 31.35 +/- 4.3 U glandular kallikrein-like amidolytic
      activity/mg protein toward the chromogenic peptide substrate S-2266 (1 U is
      defined as the amount of p-nitroaniline liberated by 10 ng rat urinary
      kallikrein). Using an enzyme-linked immunosorbent assay with sheep serum raised
      against rat urinary kallikrein, the glandular kallikrein concentration of FPI was
      estimated to be 4.56 +/- 0.857 micrograms/mg protein. Upon Western blot analysis,
      FPI gave a positive band of 45,000 in the presence of beta-mercaptoethanol. In
      the absence of beta-mercaptoethanol, a band of 138,000 was observed, indicating
      that in FPI, kallikrein is present bound to a high mol wt binding protein. These
      results strongly indicate the presence of glandular kallikrein in rabbit fetal
      placentae.

PMID- 1396323
TI  - Plasma corticotropin-releasing factor concentrations in the baboon during
      pregnancy.
AB  - We have studied the secretion of placental CRF during pregnancy in the baboon, an
      animal model with many similarities to human pregnancy. Plasma CRF was measured
      in two groups of animals. In group 1, studies were performed in six anesthetized
      animals beginning 8 days postconception. In group 2, studies were performed in
      five unanesthetized chronically catheterized maternal and five fetal animals in
      the latter third of pregnancy. In the first study beginning early in pregnancy,
      CRF was undetectable in all animals on days 8 and 15 postconception. Plasma CRF
      became detectable in two animals on day 24 and in the remaining four on day 30.
      Plasma CRF rose significantly to a mean of 810 +/- 160 pg/ml at 37 days gestation
      (F = 4.20; P < 0.001). Mean maternal plasma CRF was 2452 +/- 1120 pg/ml on day 44
      and remained elevated, with a great deal of variability between subjects, until
      the end of the study period (128 days of gestation). Samples in this group were
      obtained after ketamine sedation. The effect of ketamine on CRF was studied in
      three chronically catheterized animals. Samples were obtained before and 2, 4, 6,
      and 24 h after ketamine administration (40 mg, iv). The baseline CRF
      concentration was 1168 +/- 131 pg/ml and did not change significantly over the
      time period studied. In the second study in the chronically catheterized animals,
      maternal plasma CRF was 1990 +/- 680 pg/ml at 131-140 days gestation and remained
      elevated until near term at 170 days (term = 175-180 days). Within 24 h after
      birth, plasma CRF became undetectable (< 60 pg/ml). CRF was also measured in
      chronically catheterized fetal baboons. The mean CRF concentration was 614 +/-
      224 pg/ml at 131-140 days and remained in this range until the end of the period
      studied (151-160 days gestation). To characterize the CRF immunoactivity in
      maternal baboon plasma, Sephadex chromatography was performed on an 8.4-ml plasma
      sample obtained at 160 days gestation. The majority of the CRF immunoactivity
      eluted in the same position as synthetic human CRF. We conclude that high levels
      of placental CRF are present in the systemic circulation of the maternal and
      fetal baboon during pregnancy. In contrast to human pregnancy, which is
      characterized by an exponential rise in maternal CRF concentrations in the final
      weeks before delivery, an exponential rise in maternal baboon CRF concentrations
      occurs early in pregnancy.

PMID- 1396324
TI  - Effects of selenium deficiency on thyroid hormone economy in rats.
AB  - In selenium-deficient rats, peripheral T4 to T3 conversion is markedly decreased
      due to the loss of the selenoprotein, type I iodothyronine 5'-deiodinase (5'D-I).
      Despite the marked increase in circulating T4 that results from this loss of 5'D
      I, serum T3 concentrations in selenium-deficient rats remain in the normal range.
      To determine the physiological mechanism(s) that maintains circulating T3 when
      peripheral T4 to T3 conversion is impaired, we examined the interrelationships
      between selenium intake and the metabolism of T3 and T4 in the rat. In euthyroid
      rats, selenium deficiency caused the expected loss of 5'D-I, with a 52% increase
      in serum T4, which paralleled an increase in the T4 biological half-life.
      Consistent with the prolonged t1/2 of T4, short term thyroidectomy (48 h) in
      selenium-deficient rats failed to decrease serum T4 concentrations to the levels
      observed in short term thyroidectomized, selenium-supplemented rats. Short term
      thyroidectomy also caused an expected 33% decrease in liver 5'D-I and a 44%
      increase in brain type II iodothyronine 5'-deiodinase (5'D-II) activities in
      selenium-supplemented rats. However, in selenium-deficient rats, short term
      thyroidectomy did not affect 5'D-I or 5'D-II activities. In contrast to the
      selenium-dependent changes in circulating T4 levels, little or no change in
      circulating T3 concentrations occurred. There was a 20% increase in the T3 half
      life in selenium-deficient rats. The serum T3 sulfate concentration was
      increased, and T3 deiodination was reciprocally decreased in the selenium
      deficient rats. These data suggest that increased T3 sulfate generation in
      selenium-deficient rats may lead to greater T3 availability through enterohepatic
      recycling of the iodothyronine and may explain why there are only minor changes
      in serum T3 concentrations in selenium-deficient rats.

PMID- 1396325
TI  - Growth hormone- and prolactin-binding proteins in mammalian serum.
AB  - The present study was undertaken to characterize the species specificity and
      diversity of lactogenic and somatogenic binding to serum among mammals and to
      classify GH-binding protein (GH-BP) in this group of species. Animal sera were
      characterized on the basis of human (h) GH and bovine (b) PRL binding levels,
      binding specificity toward GHs and PRLs, binding affinity constant (Ka), and the
      ability of a monoclonal antirabbit GH receptor antibody (MAb-7) to inhibit the
      binding to serum. Analyses of the results yielded a classification of the
      mammalian sera into five types of GH binding, which we elected to call GH-BP. The
      guinea pig had undetectable levels of GH-BP and was labeled type 0. Type I GH-BP
      was found in the mouse and the rat. hGH binding to GH-BP of type I serum was of
      low affinity (1.2-3.9 x 10(8) M-1) with high IC50 (approximately 100 ng/tube) and
      was purely somatogenic in nature. Type II GH-BP was found in the goat, sheep, and
      cow. Their IC50 of hGH binding was approximately 4-fold lower than that of type I
      GH-BP. Their binding of hGH was relatively specific and only marginally displaced
      by the PRLs. Type III GH-BP was found in the rabbit, horse, cat, dog, and pig.
      These animals' sera had high affinity binding toward hGH (4.7-9.2 x 10(9) M-1),
      with low IC50 (approximately 2 ng/tube) and dominant lactogenic binding. The
      great similarity of type III GH-BPs was further stressed by the ability of MAb-7
      to inhibit [125I]hGH binding to all type III sera, but not to the other mammalian
      sera tested. Type IV GH-BP was found in the human and rhesus monkey sera. These
      were characterized by binding affinities that were intermediate between those for
      types II and III GH-BP and by the inability of nonprimate GHs to compete with hGH
      binding. To directly confirm the potent effect of the lactogenic hormones in type
      III GH-BP, the specific binding of bPRL to sera of type III animals was studied.
      [125I]bPRL-specific binding was determined under optimized assay conditions and
      was the highest in rabbit serum, with the following rank order being observed:
      rabbit >> horse = dog = pig > cat. Scatchard analysis of [125I]bPRL binding
      revealed linear plots with similar affinity constants (Ka) of 1.7-3.3 x 10(9) M
      1.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1396326
TI  - The role of protein kinase-C in gonadotropin-induced ovulation in the in vitro
      perfused rabbit ovary.
AB  - Tumor-promoting phorbol esters are believed to affect ovarian granulosa cell
      progesterone and prostaglandin (PG) production and possibly ovulation by
      activating protein kinase-C (PKC). The effects of phorbol esters and PKC
      inhibitors on ovulation, progesterone, and PG production were examined in an in
      vitro perfused rabbit ovary. The effect of tranexamic acid, an inhibitor of the
      conversion of plasminogen activator to plasmin, on phorbol ester-induced
      ovulation was also examined. Phorbol 12,13-dibutyrate (PdBU), a PKC stimulator,
      induced ovulation in a dose-related manner in the absence of gonadotropins (56%,
      200 nM PdBU; 0%, 0 nM PdBU; P < 0.05). Perfusate progesterone levels were
      increased only after 600 nM PdBU treatment, and perfusate PGF2 alpha, PGE2, and 6
      keto-PGF1 alpha were increased in a dose-dependent fashion (P < 0.05).
      Staurosporine, a potent inhibitor of the catalytic domain of PKC, and calphostin
      C, a specific inhibitor of the diacylglycerol-binding region, inhibited hCG
      induced ovulation in a dose-related manner. Gonadotropin-induced ovulation
      decreased from 73% without staurosporine to 19% with 1.0 microM staurosporine (P
      < 0.01). Calphostin-C reduced ovulatory efficiency from 60% to 24% (P < 0.01).
      However, neither inhibitor decreased progesterone or PGF2 alpha production by
      ovaries exposed to hCG. hCG-induced oocyte maturation was also unaffected by
      exposure to either staurosporine or calphostin-C. Tranexamic acid reduced phorbol
      ester-induced ovulatory efficiency from 67% to 37% (P < 0.05). These findings
      demonstrate that the calcium-dependent PKC pathway is instrumental in
      gonadotropin-mediated follicular rupture in the rabbit. Although PGs may play an
      important role in ovulation, they do not appear to be directly responsible for
      PKC-mediated follicular rupture.

PMID- 1396327
TI  - Glyburide and tolbutamide induce desensitization of insulin release in rat
      pancreatic islets by different mechanisms.
AB  - Insulin secretion was studied in rat pancreatic islets after 24-h exposure to
      various glyburide or tolbutamide concentrations. Glucose-induced insulin release
      was significantly (P < 0.05) reduced in islets cultured with 0.1 microM glyburide
      or 100 microM tolbutamide (2098 +/- 187, 832 +/- 93, and 989 +/- 88 pg/islet.h in
      control, glyburide-exposed, and tolbutamide-exposed islets, respectively). When
      glyburide-treated islets were stimulated with glyburide or tolbutamide, insulin
      release was also impaired compared to that in control islets (P < 0.05). In
      contrast, tolbutamide-exposed islets showed an impaired response to tolbutamide,
      but a normal response to glyburide. To investigate the mechanism of the
      sulfonylurea-induced impairment of insulin secretion, we measured insulin release
      and Rb+ efflux (a marker of the K+ channel activity) in a perifusion system and
      islet Ca2+ uptake under static conditions. Insulin release in response to 16.7 mM
      glucose increased in control islets from 9.4 +/- 1.1 to 131 +/- 19 pg/islet.min
      (first phase secretion peak). Simultaneously, the fractional 86Rb+ efflux
      declined from 0.015 +/- 0.002% to 0.006 +/- 0.001% (change in decrement, -63.5%).
      Glucose-induced insulin release in glyburide- and tolbutamide-treated islets was
      significantly reduced (first phase peak, 22.1 +/- 5 and 39.7 +/- 8 pg/islet.min,
      respectively; P < 0.05), and the fractional 86Rb+ efflux decrement was -21 +/- 6%
      for glyburide (P < 0.005 vs. control islets) and -65 +/- 4% (not different from
      control) for tolbutamide. When glyburide- or tolbutamide-exposed islets were
      stimulated with the corresponding sulfonylurea, insulin release was impaired
      compared to that in control islets (P < 0.05), but, again, 86Rb+ efflux was
      impaired (P < 0.05) only in glyburide-exposed islets. When 45Ca2+ uptake was
      studied, the increase in glucose concentration from 2.8 to 16.7 mM increased
      calcium uptake in control islets from 1.76 +/- 0.58 to 7.27 +/- 1.36 pmol/islet.2
      min (n = 4). Preexposure to 0.1 microM glyburide did not change calcium uptake at
      a glucose concentration of 2.8 mM (1.44 +/- 0.45 pmol/islet.2 min) but
      significantly reduced calcium uptake stimulated by 16.7 mM glucose (3.21 +/- 0.35
      pmol/islet.2 min; n = 4; P < 0.005 compared to control islets). In contrast,
      preexposure to 100 microM tolbutamide did not change either basal or glucose
      stimulated calcium uptake (1.44 +/- 0.45 and 6.90 +/- 0.81 pmol/islet.2 min,
      respectively; n = 4). These data show that in vitro chronic exposure of
      pancreatic islets to the sulfonylureas glyburide and tolbutamide impairs their
      ability to respond to a subsequent glucose or sulfonylurea stimulation.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1396328
TI  - Alteration in the expression of GLUT-1 and GLUT-4 protein and messenger RNA
      levels in denervated rat muscles.
AB  - Denervation induces insulin resistance of the glucose transport process in
      skeletal muscle. To determine whether this is due to alterations in the
      expression of muscle glucose transporters (GLUT) in different fiber types, we
      evaluated the amount of GLUT-1 and GLUT-4 protein and messenger RNA (mRNA) in
      extensor digitorum longus (EDL) and soleus at 1, 2, and 3 days after sciatotomy.
      Denervation elevated the basal rate of 2-[1,2-3H]deoxy-D-glucose (2-DOG) uptake
      in the EDL and decreased the insulin-stimulated DOG uptake in both muscles.
      Denervation after 1 day did not modify the GLUT-1 or the GLUT-4 protein level in
      either muscle. However, it increased GLUT-1 mRNA by 66% and decreased GLUT-4 mRNA
      by 70% in the EDL, but not in the soleus (P < 0.05). After 2 days of denervation,
      by which time GLUT-1 mRNA was increased 2-fold and GLUT-4 mRNA was reduced by
      70%, we observed a 2-fold increase in GLUT-1 protein (P < 0.01) in the EDL and a
      40-45% decrease in GLUT-4 protein in both muscles (P < 0.01). These results
      indicate that modifications in the expression of GLUT-1 and GLUT-4 protein cannot
      explain the insulin resistance of the glucose transport process in the EDL or
      soleus 1 day after denervation. After 2 days of denervation, however, alterations
      in GLUT-1 and GLUT-4 protein levels may contribute to the change in basal and
      insulin-stimulated DOG uptake in both the EDL and the soleus muscles.

PMID- 1396329
TI  - Monoclonal antibodies specific for rat relaxin. VII. Passive immunization with
      monoclonal antibodies throughout the second half of pregnancy prevents
      development of normal mammary nipple morphology and function in rats.
AB  - We recently demonstrated that relaxin-dependent development of the mammary
      nipples during the second half of pregnancy is required for pup survival during
      lactation in the rat. The two related objectives of this investigation were to 1)
      characterize the effects of endogenous relaxin on the histological modifications
      that normally occur in the mammary nipples, and 2) test the hypothesis that the
      cause of lactational failure in relaxin-deficient rats is attributable to failure
      of the nipples to grow and develop during the second half of pregnancy.
      Endogenous relaxin was neutralized by daily iv injection of a highly purified
      monoclonal antibody specific for rat relaxin (MCA1) to intact rats from days 12
      22 of pregnancy. Mammary nipples were collected on day 22 of pregnancy and
      routinely prepared for light microscopy. Tissue cross-sections (6 microns)
      obtained from the midpoint of mammary nipples were stained with either Gomori's
      trichrome stain (to visualize collagen) or orcein (to visualize elastin). Nipple
      size as well as histological characteristics of nipple cross sections were
      determined by morphometric analysis. MCA1-treated rats were significantly
      different from controls with the following parameters: shorter length of the
      nipples; smaller cross-sectional areas of the entire nipple, lactiferous duct
      lumen, and blood vessels; greater percentage of the analysis field composed of
      collagen; lower percentage of the analysis field composed of amorphous ground
      substance; and longer elastin fibers. To test the hypothesis that the cause of
      lactational failure in relaxin-deficient rats is attributable to the failure of
      nipples to grow and develop, MCA1 and control rats were cesarean sectioned
      between 2100-2400 h on day 22 of pregnancy, and lactation was examined using
      normal foster pups from intact donor females. Unlike pups fostered to controls,
      pups fostered to MCA1-treated dams failed to grasp the nipples, stimulate PRL
      release, or have milk in their abdomens. This study demonstrates that endogenous
      relaxin promotes not only growth, but also modifications of the histological
      characteristics of the nipple that are consistent with relaxin's effects on the
      cervix and mammary glands. Additionally, this study provides evidence that
      lactational failure in relaxin-deficient rats is attributable to the small size
      and different histology of the mammary nipples, which results in the inability of
      the pups to attach to the nipple, stimulate PRL release, and obtain milk from the
      dams.

PMID- 1396330
TI  - Substitution of cysteine for selenocysteine in type I iodothyronine deiodinase
      reduces the catalytic efficiency of the protein but enhances its translation.
AB  - Type I iodothyronine 5' deiodinase (5'DI) contains selenocysteine, encoded by a
      UGA codon, and this amino acid is essential for maximum catalytic efficiency in
      this enzyme. We recently showed that translation of UGA as selenocysteine in this
      protein requires a specific sequence of about 250 nucleotides in the 3'
      untranslated region of the messenger RNA. Translation of a 5'DI cysteine mutant
      does not require the 3' untranslated region. To examine both the efficiency of
      UGA codon recognition and the relative catalytic efficiency of selenocysteine vs.
      cysteine in 5'DI, we used bromoacetyl 125I-T3 labeling to quantitate transiently
      expressed selenocysteine (wild type) and cysteine containing type I iodothyronine
      deiodinases in transfected COS-7 and JEG-3 cell lines. Kinetic analyses of the
      same cell sonicates were performed to determine the apparent maximum velocity and
      Michaelis-Menten constant values for reverse T3 5' deiodination. COS-7 cells
      express the cysteine mutant protein at about 20-fold and JEG-3 cells about 400
      fold higher levels than the selenoenzyme. However, in both cell types, the
      apparent catalytic constant values were at least 100-fold higher for the wild
      type enzyme, compared with the cysteine mutant. These results indicate that cell
      lines differ markedly in their capacity to translate UGA-containing messenger
      RNAs. The much higher catalytic constant values for the selenium-containing
      enzyme illustrate the biochemical advantage of this element as compared with
      sulfur in the catalysis of iodothyronine deiodination.

PMID- 1396331
TI  - Interleukin-1 stimulates deoxyribonucleic acid synthesis in immature rat Leydig
      cells in vitro.
AB  - The number of interstitial macrophages in the testis fluctuates according to age,
      increasing gradually during prepubertal development to reach 15-20% in the
      interstitial compartment in the adult rat. These macrophages are in close
      morphological association with Leydig cells. Macrophage products, interleukin-1
      (IL-1) and tumor necrosis factor alpha stimulate and/or inhibit steroid
      production in cultures of Leydig cells. We have studied the effects of macrophage
      products on DNA synthesis in rat Leydig cells to investigate a possible paracrine
      role of testicular macrophage products on the proliferation of Leydig cells.
      Leydig cells isolated from 10-, 20-, and 70-day-old rats were cultured for 48 h
      in serum-free medium, washed, and treated with different cytokines for 18 h. The
      medium was then removed, fresh medium containing 0.5 microCi [3H]thymidine was
      added, and cells were incubated for 4 h prior to determining the incorporation of
      [3H]thymidine into DNA. Human recombinant IL-1 beta caused a dose-dependent
      stimulation in the incorporation of [3H]thymidine into DNA in the Leydig cells
      from 10- and 20-day-old rats but had no effect on DNA synthesis in interstitial
      cells from adult rats. Maximum stimulation of DNA synthesis in immature Leydig
      cells was observed with 1-2 ng/ml IL-1 beta. Autoradiography after incubation
      with [3H]thymidine showed a dramatic increase in the number of labeled Leydig
      cells after treatment with IL-1 beta (19.27 +/- 3.77% vs. 1.44 +/- 0.52% in
      control cultures) indicating that IL-1 beta recruited more cells to enter the
      cell cycle and initiate DNA synthesis. Human recombinant IL-1 alpha and tumor
      necrosis factor alpha also caused significant stimulation of DNA synthesis in
      Leydig cells but these cytokines were much less potent (1-10%) than IL-1 beta. IL
      1 beta enhanced the effects of maximally effective concentrations of growth
      promoting agents previously known to stimulate DNA synthesis in immature rat
      Leydig cells, i.e. human CG, steroidogenesis-inducing protein, and transforming
      growth factor alpha plus insulin. On the basis of these results it is concluded
      that IL-1 may play an important role in the proliferation of Leydig cells during
      prepubertal development in immature rats.

PMID- 1396332
TI  - U-73122, an aminosteroid phospholipase C antagonist, noncompetitively inhibits
      thyrotropin-releasing hormone effects in GH3 rat pituitary cells.
AB  - TRH increases cytosolic-free calcium ([Ca2+]i) by activating phospholipase C(PL
      C), which induces phosphoinositol hydrolysis, leading to Ca2+ mobilization from
      inositol trisphosphate (IP3) sensitive stores, and by increasing Ca2+ influx.
      Increases in [Ca2+]i stimulate PRL secretion. We investigated the effects of U
      73122, an aminosteroid inhibitor of PL-C dependent processes, on TRH-stimulated
      second messenger pathways and on PRL secretion in GH3 rat pituitary cells.
      [Ca2+]i was monitored by Indo-1 fluorescence, and IP3 and metabolites separated
      on ion exchange columns. In Ca(2+)-free buffer, [Ca2+]i was 96 +/- 6 nM and
      increased to 323 +/- 23 nM (P less than 0.001) after TRH (100 nM). U-73122 dose
      dependently inhibited the TRH effect (IC50 = 967 nM; complete inhibition at 3-5
      microM). Subsequent addition of monensin (100 microM) increased [Ca2+]i from 107
      +/- 4 to 142 +/- 4 nM (P < 0.001), confirming our previous findings of a non-TRH
      regulated Ca2+ pool in GH3 cells. Pretreatment (15 sec) with U-73122 partly
      inhibited the TRH effect on [Ca2+]i; complete suppression occurred with 70 sec of
      pretreatment. An inactive analog (U-73343) had no inhibitory effect at 5 microM.
      U-73122 acted noncompetitively, as the mean maximum velocity (expressed as
      percent increase in [Ca2+]i after TRH) was reduced from 225 to 91 while the
      Michaelis-Menten constant for TRH was unchanged (15.4 vs. 13.8 nM, n = 3). Of
      note, U-73122, at 3-5 microM, increased basal [Ca2+]i from 109 +/- 5 to 120 +/- 5
      nM (P less than 0.001). In 1.3 mM Ca2+ buffer containing nifedipine (1 microM)
      and verapamil (50 microM), similar effects of U-73122 (5 microM) were observed on
      basal and TRH-stimulated [Ca2+]i. IP3, IP2, and IP1 increased to 241 +/- 12%, 148
      +/- 23%, and 167 +/- 39% of control, 30 sec after TRH (100 nM); these responses
      were prevented by 1 microM U-73122. At 5 microM, U-73122 also significantly
      increased IP3 levels. TRH (100 nM) increased 4-h PRL secretion from 16.3 +/- 1.4
      to 27.6 +/- 3.2 ng/well (P less than 0.05). U-73122 (5 microM) increased basal
      PRL secretion to 35.9 +/- 3.2 ng/well (P less than 0.05), but abolished the TRH
      effect. In contrast, U-73343 (with Ca2+ channel blockers) did not inhibit the TRH
      effect on PRL (control: 24.3 +/- 2.1; TRH: 51.0 +/- 6.3 ng/well).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 1396333
TI  - Parathyroid hormone activates protein kinase C of pancreatic islets.
AB  - Pancreatic islets are targets for PTH. The acute exposure of the islets to PTH
      results in a rise in their cytosolic calcium ([Ca2+]i). It also stimulates
      insulin secretion in a manner similar to that produced by phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC),
      suggesting that the hormone may stimulate the activity of this enzyme. The
      present study examined the effect of PTH (1-34) on both cytosolic and membrane
      bound PKC activity of pancreatic islets and compared it with that of glucose and
      TPA. In the basal state, PKC activity is predominantly found in the cytosol. Both
      PTH or high glucose concentration caused a significant increase in membrane-bound
      and total PKC activity, whereas cytosolic enzyme activity remained unchanged. The
      effects of these two agonists peaked at 5 min and declined thereafter. The effect
      of PTH on PKC activity was abolished by the PTH antagonist ([Tyr-34] bovine PTH
      (7-34) NH2). In contrast, TPA induced a rise in membrane-bound PKC activity with
      simultaneous decrease in cytosolic pool of PKC without a change in total PKC
      activity. Removal of calcium from the incubation media resulted in partial and
      significant loss of PTH-induced rise in membrane-bound PKC activity. The data
      demonstrated that 1) PTH stimulate PKC activity of pancreatic islets in a manner
      similar to that of glucose, 2) both of the agonists increases total PKC activity
      of islets and translocation of the enzyme activity to the membranes of the
      islets, and 3) the effect of PTH is mediated, in part, by its ability to augment
      calcium entry into the islets and is most likely receptor mediated.

PMID- 1396334
TI  - Effect of N-methyl-D,L-aspartate on isolated rat somatotrophs.
AB  - The effect of excitatory amino acid receptor agonists on GH secretion was tested
      in isolated male rat somatotrophs. N-Methyl-D,L-Aspartate (NMDA) had a dose
      dependent stimulatory effect on GH secretion in perifused somatotrophs. The
      effect was observed already during the first minute after exposure to NMDA and
      was reversible after its omission. The effect of 1 microM NMDA was inhibited by
      the NMDA receptor antagonists 10 microM AP7 and 5 microM MK801, and by 5 microM
      dextromethorphan. L-Glutamate, 100 microM, and 100 microM kainic acid also
      stimulated GH secretion. The stimulatory effect of NMDA on GH release was
      paralleled by an increase in 45Ca efflux and an increase in somatotroph
      intracellular calcium concentration. Efflux of 86Rb (tracer for potassium) was
      not affected by NMDA. It is concluded that excitatory amino acids can stimulate
      GH secretion in rats through a direct effect on the somatotrophs.

PMID- 1396335
TI  - Differential regulation of proenkephalin expression in astrocytes by cytokines.
AB  - Astrocytes have previously been shown to respond to cytokines such as interleukin
      1 beta, tumor necrosis factor-alpha, and gamma-interferon from multiple sources
      including microglia and astrocytes. Recently, astrocytes have also been shown to
      express the opioid precursor gene proenkephalin and proenkephalin-derived
      peptides. The objectives of the current study were to determine if immune
      cytokines regulate proenkephalin gene expression in primary cultures of neonatal
      rat cerebral astrocytes. Northern analysis of RNA from primary cultures of
      neonatal rat cerebral astrocytes indicated that proenkephalin transcript levels
      were decreased by approximately 50% with gamma-interferon treatment and increased
      approximately 100% by treatment with both tumor necrosis factor-alpha and
      interleukin-1 beta relative to untreated controls. Tumor necrosis factor-alpha
      treatment was unable to reverse the inhibitory effect of gamma-interferon
      pretreatment on proenkephalin messenger RNA levels in the astrocytes. In
      contrast, expression of the constitutively expressed glutamine synthetase gene
      was not altered by either tumor necrosis factor-alpha or gamma-interferon
      treatment. These cytokines also regulate the secretion of proenkephalin-derived
      peptides from astrocytes. The levels of immunoreactive Met-enkephalin-Arg6-Phe7
      were increased by approximately 50% with tumor necrosis factor-alpha and
      decreased by approximately 40% with gamma-interferon relative to untreated
      controls. Tumor necrosis factor-alpha was again unable to reverse the inhibitory
      effect of gamma-interferon pretreatment on the secretion of proenkephalin-derived
      peptides. These results provide additional support for the hypothesis that
      rapidly proliferating astrocytes may serve an important and pivotal role in
      mediating the bi-directional neuroimmune interactions during central nervous
      system disease, infection, or trauma.

PMID- 1396336
TI  - Growth hormone synergizes with serum growth factors in inducing c-fos
      transcription in 3T3-F442A cells.
AB  - GH is a major regulator of growth and metabolism, but cellular effects of GH
      alone have been difficult to demonstrate. Accordingly, suggestions have arisen
      that GH works in conjunction with other agents in producing its characteristic
      long term biological effects. In 3T3-F442A cells, in addition to eliciting long
      term changes, GH rapidly increases the transcription of c-fos. The present study
      uses this rapid response to examine whether GH interacts with other factors early
      in its action, and whether such interactions lead to changes in gene expression.
      The induction of c-fos mRNA in response to the combination of GH (2.2 nM) and 10%
      calf serum or fetal calf serum was more than 3 times the additive effects of GH
      and either of the sera alone, indicating synergism between GH and serum. Insulin
      like growth factor-I (IGF-I), which also induces c-fos, had an effect with GH
      that was greater than the additive responses to the two agents. Nuclear run-off
      experiments indicated that the synergism between GH and IGF-I occurred at the
      level of transcription of c-fos. However, synergism between GH and serum in
      inducing c-fos transcription was greater than synergism between GH and IGF-I,
      suggesting that factors in addition to IGF-I contribute to the interaction of GH
      with serum. Insulin and fibroblast growth factor also synergized with GH in
      inducing c-fos expression. Platelet-derived growth factor and epidermal growth
      factor appeared to induce c-fos additively with GH, suggesting that different
      types of interactions occur between GH and the various growth factors. In
      inducing c-jun, which works coordinately with c-fos in transcriptional
      regulation, the effect of GH was additive with that of IGF-I and synergistic with
      that of serum. These findings indicate that early in its action, GH interacts
      with other growth factors in inducing protooncogene expression in 3T3-F442A
      cells. Such interactions between GH and serum or specific growth factors result
      in synergistic induction of the expression of c-fos. These findings suggest a
      generalized mechanism in which a major contribution of GH to cellular growth
      regulation is to synergize with other growth-promoting signals early in
      transduction of such signals in targets cells, resulting in enhanced gene
      transcription.

PMID- 1396337
TI  - Effects of porcine follicular fluid, inhibin-A, and activin-A on goldfish
      gonadotropin release in vitro.
AB  - Inhibin and activin are important reproductive regulators in mammalian species
      and have been demonstrated to be highly conserved in structure. The present study
      examines the effects of porcine follicular fluid (pFF; a crude inhibin and
      activin preparation) and purified porcine inhibin-A and activin-A on goldfish
      gonadotropin-II (GTH-II) release. In studies using primary cultures of dispersed
      goldfish pituitary cells in static incubation, treatments with pFF, inhibin-A,
      and activin-A for 10 h caused dose-dependent increase in GTH-II release. In
      perifusion studies using goldfish pituitary fragments, basal GTH-II release was
      significantly elevated after 12-h exposure to 500 micrograms/ml pFF. Furthermore,
      GnRH-induced GTH-II secretion was potentiated by pretreatment with pFF. When pFF
      was applied in the form of 5-min pulses, a rapid dose-related stimulation of GTH
      II was observed. Similarly, challenges with 2-min pulses of 15, 150, and 1500 pM
      inhibin-A and activin-A stimulated GTH-II release by goldfish pituitary fragments
      in a rapid and dose-dependent manner. This acute stimulatory action of inhibin on
      goldfish GTH-II release was completely abolished after pretreatment with specific
      inhibin antibodies. The acute actions of inhibin and activin on GTH-II release
      are probably not due to the release of endogenous GnRH from nerve terminals in
      the pituitary fragments or binding to the GnRH receptors. First, a specific GnRH
      antagonist did not block the actions of inhibin and activin. Second, dopamine, a
      potent inhibitor of GnRH-stimulated GTH-II secretion in goldfish, was only
      partially effective in decreasing inhibin- and activin-induced GTH-II release.
      Third, the stimulatory effects of inhibin and GnRH on GTH-II release were
      additive. These lines of evidence also indicate that the mechanisms mediating
      inhibin and activin stimulation of goldfish GTH-II release may be somewhat
      different from those of GnRH. These results demonstrate that in contrast with the
      usual inhibitory effects of inhibin on GTH release in mammals, both inhibin and
      activin exert long term and acute stimulatory actions on GTH-II release in the
      goldfish.

PMID- 1396338
TI  - Involvement of protein kinase-C in the mitogenic effect of insulin-like growth
      factor-I on rat astrocytes.
AB  - Insulin-like growth factor-I (IGF-I) stimulates the proliferation of many cell
      types, including astrocytes. Astrocytes are a population of brain cells highly
      enriched in IGF-I receptors, which unlike neurons, retain the ability to
      proliferate in the adult brain. Although astrocyte proliferation in response to
      IGF-I is well documented, the intracellular mechanisms that mediate this
      phenomenon are poorly defined. Interestingly, activation of protein kinase-C
      (PKC) by IGF-I has been observed in several cell types. In this report we first
      characterized the mitogenic effects of IGF-I on highly purified type I rat
      astrocyte cultures. Next, we determined whether IGF-I activates PKC in our
      cultures. Finally, since astrocyte proliferation is stimulated by both IGF-I and
      the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA), we decided to test
      the possible involvement of PKC in the mitogenic activity of IGF-I on astrocytes.
      IGF-I stimulated the DNA synthesis rate in rat astrocytes. Analysis of the time
      course revealed that IGF-I (10 nM) induces maximal stimulation of [3H]thymidine
      incorporation (a 4-fold increase) 16-18 h after exposure. TPA also stimulated
      mitogenesis in our cultures. The dose-response of [3H]thymidine incorporation
      induced by IGF-I and TPA indicated that 10 nM was the lowest concentration
      producing a maximal effect for both agents. Analysis of proteins by Western blot
      revealed that 10 nM IGF-I translocates PKC(alpha), the predominant PKC isoform in
      astrocyte cultures, from the cytosol to the membrane fraction within 20 min. A
      similar activation of PKC was achieved with 100 nM TPA. When astrocytes were
      exposed to IGF-I (10 nM) and TPA (10 nM) in combination, [3H]thymidine uptake was
      significantly higher than the uptake induced by either IGF-I (10 nM) or TPA (10
      nM) alone. However, the effect of IGF-I plus TPA was not fully additive. In a
      second experiment, the mitogenic effect of IGF-I was partially abolished in cells
      depleted of PKC by preincubation with high concentrations of TPA (300 nM).
      Finally, incubation of astrocytes with the PKC inhibitor H-7 at 20 microM, a
      concentration that completely blocked the mitogenic action of TPA, only reduced
      the ability of IGF-I to stimulate DNA synthesis by 50%. In summary, our results
      demonstrate that IGF-I can rapidly activate PKC in astrocytes, and that PKC
      activation is involved in the mitogenic effect of IGF-I on these cells. However,
      we conclude that IGF-I also stimulates astrocyte proliferation through PKC
      independent pathways.

PMID- 1396339
TI  - Zonal distribution and regulation of adrenal renin in a transgenic model of
      hypertension in the rat.
AB  - The hypertensive transgenic rat [TGR (mRen-2)27] is a genetic model of
      hypertension in which transfection of the Ren-2 mouse renin gene into rats
      results in severe hypertension. These transgenic rats express a high level of
      renin in the adrenal gland, and the hypertension is ameliorated by treatment with
      angiotensin-converting enzyme inhibitors. In this study we investigated the
      distribution of adrenal renin in the TGR rat and examined the regulation of
      adrenal renin in a monolayer culture of adrenal cells. High concentrations of
      active renin and prorenin were found in the adrenal capsular (glomerulosa) and
      decapsular (fasciculata-medullary) portions of the TGR adrenal. This is in
      contrast with the Sprague-Dawley (S-D) rat, in which adrenal renin is found
      mostly in the active form and located primarily in the glomerulosa cells. The
      zonal distribution of aldosterone was also different in the TGR, with substantial
      amounts of aldosterone in the zona fasciculata as well as in the glomerulosa,
      while in the S-D rat, aldosterone is limited to the zona glomerulosa. In the
      primary monolayer culture of glomerulosa cells, TGR cells had significantly
      higher levels of active renin and prorenin and showed an increased response to
      ACTH and high potassium in the medium. Renin activity in the medium was
      predominantly in the form of prorenin and significantly higher than that in the S
      D rat. Cultured fasciculata cells from TGR also produce renin that is stimulated
      by ACTH, but not by a high potassium concentration. Renin activity in the adrenal
      homogenate, medium, and plasma from TGR rats was completely inhibited by the
      renin inhibitor (CP 71362; 1 microM), but only slightly inhibited (12.3 +/- 3%)
      by a monoclonal antibody that inhibits renin activity from S-D rat tissues by
      79.2 +/- 2.5%, suggesting that renin in the plasma and adrenal glands from TGR
      appears to derive primarily from mouse renin. In conclusion, the TGR (mRen-2)27
      rats have higher than normal levels of adrenal renin, and the cultured cells show
      an exaggerated renin response to ACTH and potassium. The distribution of the
      renin enzyme in the adrenal zones of the TGR is similar to the distribution of
      mouse adrenal renin.

PMID- 1396340
TI  - Growth hormone (GH) binding protein and GH interactions in vivo in the guinea
      pig.
AB  - GH binding proteins (GHBPs) are present in the blood of several species and by
      complexing with circulating GH may alter its clearance and distribution. The
      actions of human GHBP (hGHBP) have hitherto been studied indirectly via their
      effects on the clearance of hGH. In the present experiments, recombinant
      preparations of hGHBP and a shorter variant lacking exon 3 (delta 3hGHBP) were
      tested in vivo, either alone or after preincubation with recombinant hGH,
      recombinant 20K methionyl-hGH, or rat GH. Multiple serial blood sampling was
      performed in conscious chronically cannulated guinea pigs and both GHBP and GH
      variants monitored in the same samples by specific RIAs, unaffected by endogenous
      activities in this species. hGHBP, delta 3hGHBP, hGH, and 20K met-hGH (10-40
      micrograms) were all cleared rapidly when injected alone (t1/2 = 11-20 min).
      However, when the same amounts of hGHBP and hGH were incubated together for 60
      min and then injected, the clearance of both proteins was greatly prolonged (t1/2
      hGHBP = 75-94 min, hGH = 80-137 min). Similar results were obtained for hGH
      complexed with delta 3hGHBP, and over a range of GH:GHBP ratios from 0.3:1 to
      4:1. The effect was specific for 22K hGH; neither rat GH nor 20K met-hGH altered
      hGHBP clearance, nor were their clearances slowed by preincubation with hGHBP.
      Rapid complex formation also could be demonstrated in vivo. Injections of hGH 30
      min after delta 3hGHBP, or vice versa, altered the established plasma
      disappearance curve of hGHBP, and hGH clearance was slowed in parallel. During a
      continuous infusion of hGH to steady state, injections of delta 3hGHBP increased
      plateau hGH concentrations by forming a delta 3hGHBP/hGH complex in the
      circulation. These experiments show that the conscious chronically cannulated
      guinea pig provides a useful model in which the in vivo interaction between hGHBP
      and hGH can be studied dynamically. The results imply that the location, extent,
      and rate of complex formation between GHBP and GH may be an important determinant
      of the passage of GH between the intra- and extravascular compartments, which
      could affect the pattern of tissue exposure to GH.

PMID- 1396341
TI  - Prolactin-induced proliferation of the Nb2 T-lymphoma is associated with protein
      kinase-C-independent phosphorylation of stathmin.
AB  - Phosphorylation of stathmin, a 19-kDa protein found in many tissues, has been
      linked to cell differentiation and proliferation. This protein is present in
      lymphocytes, and both phosphorylation and expression of stathmin are regulated by
      lymphotropic agents. In this study an antibody specific for stathmin was used to
      examine phosphorylation in response to PRL. The results suggest that PRL
      stimulates stathmin phosphorylation in the Nb2 lymphoma and that phosphorylation
      correlates with PRL-induced cell proliferation. Stathmin expression does not
      change substantially as PRL-stimulated Nb2 cells move through the cell cycle and
      enter into the S-phase. Thus, stathmin phosphorylation, but not expression, is
      regulated by PRL. Activation of protein kinase-C (PKC) in Nb2 cells also induces
      phosphorylation of stathmin, but PKC does not appear to mediate phosphorylation
      in response to PRL. The pattern of phosphorylation in response to 12-O
      tetradecanoylphorbol-13-acetate differs from that in response to PRL, and down
      regulation of PKC does not inhibit PRL-induced phosphorylation or proliferation.
      In addition to stathmin, PRL increases phosphorylation of a group of stathmin
      like proteins. Phosphorylation of these proteins also correlates well with PRL
      induced proliferation. Taken together, the results suggest that phosphorylation
      of stathmin and stathmin-like proteins may mediate some actions of PRL in Nb2
      cells. The results further suggest that activation of PKC is not an important
      early event in PRL-stimulated mitogenesis in Nb2 cells.

PMID- 1396342
TI  - Diacylglycerol inhibits potassium-induced calcium influx and insulin release by a
      protein kinase-C-independent mechanism in HIT T-15 islet cells.
AB  - We reported previously that in pancreatic islet cells, certain diacylglycerols
      (DGs) evoke increases in cytosolic calcium ([Ca2+]i), mainly by intracellular
      mobilization. We now examined the effects of DGs on the increase in [Ca2+]i due
      to Ca2+ influx. In the insulin-secreting HIT T-15 islet cell line, cell membrane
      depolarization using 40 mM KCl evoked a 2- to 3-fold increase in [Ca2+]i, which
      lasted several minutes. A cell-permeable DG, 1,2-dioctanoylglycerol (DiC8; 10
      microM) induced a 12 +/- 4% rise in [Ca2+]i, which did not occur in the absence
      of extracellular Ca2+ or in the presence of verapamil; this effect was not
      protein kinase-C (PKC) dependent, because it was not altered by the addition of
      the PKC inhibitor staurosporine or by using PKC-depleted cells. When DiC8 was
      added first, the KCl-induced increase in [Ca2+]i was inhibited in a dose
      dependent manner (100% at 10-15 microM DiC8); this effect was PKC independent. At
      a concentration of 10 microM, other synthetic DGs, 1,2-dihexanoylglycerol (DiC6),
      1,2-didecanoylglycerol (DiC10), or 1-oleoyl-2-acetylglycerol, inhibited the KCl
      induced rise in [Ca2+]i to 15 +/- 4%, 47 +/- 7%, and 51 +/- 5% of the control
      value, respectively. R59022 (10 microM), which inhibits DG kinase and causes
      accumulation of endogenous DGs, inhibited the KCl-induced rise in [Ca2+]i to 2 +/
      0.2% of the control value; this inhibition was not affected by staurosporine. In
      anchored cells, KCl stimulated insulin release (959 +/- 88 microU/mg protein
      above the control value); 20 microM DiC6 or DiC8 attenuated KCl-induced insulin
      release by 68% and 31% of the control value, respectively; DiC10 or 1-oleoyl-2
      acetylglycerol had no effect. R59022 inhibited KCl-induced insulin release by 90%
      of the control value. We conclude that in HIT T-15 cells, DGs may serve as
      positive and negative modulators of [Ca2+]i, apparently by complex and PKC
      independent mechanisms. These divergent actions of DGs on islet cell Ca2+ balance
      together with the accompanying activation of PKC affect insulin release in a
      complex manner.

PMID- 1396343
TI  - Comparative mapping of human thyrotropin, gonadotropins, and free subunits with
      antipeptide antibodies.
AB  - To compare the structural topology of the human TSH to that of the structurally
      related gonadotropins, 10 peptides covering the entire primary sequence of the
      alpha- and beta-subunits of TSH were synthesized and used as antigens for the
      preparation of polyclonal antibodies. The alpha-subunit was synthesized as 4
      nonoverlapping peptides (1-25, 26-51, 49-73, 72-92) while the beta-subunit was
      segmented in 6 overlapping sequences (2-18, 10-38, 31-51, 53-76, 77-96, 92-112).
      Most of the peptide sequences were predicted to contain a putative antigenic
      determinant. All antipeptide antisera were found to bind to the corresponding
      synthetic sequence in an enzyme-linked immunosorbent assay as well as to
      denatured TSH subunits after Western blotting. The N-terminal half of the alpha
      subunit was found differentially accessible in TSH and gonadotropins compared to
      the free subunit: antipeptide-alpha 1-25 antibodies exhibited variable affinity
      for the four glycoprotein hormones whereas anti-alpha 26-51 displayed a
      remarkable recognition of free alpha-subunit. Four peptides proved to be
      accessible in the TSH beta-subunit: the N-terminal peptide (beta 2-18) elicited
      antibodies that bound to free TSH-beta and poorly to the dimer while antibodies
      against the C-terminal sequence (beta 92-112) recognized equally well free beta
      subunit and TSH. Antipeptide-beta 31-51 antibodies proved to be specific for TSH
      while the beta 53-76 contiguous peptide appeared accessible in both TSH and
      gonadotropins. The current findings therefore demonstrate that most of the
      sequences predicted to contain antigenic sites in the alpha- or the beta-subunits
      are indeed accessible at the surface of these proteins. Additionally, both
      subunits appear to contain amino acid sequences that are differentially expressed
      in TSH and gonadotropins as well as in free and combined subunits.

PMID- 1396344
TI  - Novel testis germ cell-specific transcript of the CREB gene contains an
      alternatively spliced exon with multiple in-frame stop codons.
AB  - The gene encoding the cAMP-responsive transcription factor CREB consists of
      multiple small exons some of which undergo alternative RNA splicing. We describe
      the finding of a novel transcript of the CREB gene expressed at high levels in
      the germ cells of the rat testis. The transcript contains an alternatively
      spliced exon inserted within the sequence encoding the transcriptional
      transactivation domain of CREB and this exon contains multiple in-frame stop
      codons. Furthermore, the exon is conserved in both rat and human genes (75%
      nucleotide identity). Although the function(s) of this RNA or the truncated CREB
      protein predicted to result from the translation of this unusual transcript is
      unknown, the high level of expression in the testicular germ cells and remarkable
      conservation of sequences in rat and human suggests that it may have a unique
      biological function in these cells.

PMID- 1396345
TI  - Growth response and androgen receptor expression in seminal vesicles from aging
      transgenic mice expressing human or bovine growth hormone genes.
AB  - Previous work has shown that expression of human (h) GH in transgenic mice is
      associated with significant age-related enlargement of seminal vesicles. To
      further explore this aberrant growth activity, we have characterized seminal
      vesicles from various GH transgenic lines and examined their androgen receptor
      (AR) content and distribution. Six groups of animals were initially studied:
      young adult (3-5 months) control mice, old (greater than 12 months) control mice,
      young adult hGH transgenic mice, old hGH transgenics, young adult bovine (b) GH
      transgenics, and old bGH transgenic mice. Young transgenic mice (hGH and bGH)
      possessed seminal vesicles with similar relative weights, DNA and protein
      contents, and AR levels as nontransgenic littermates. Histologically, the glands
      appeared similar. With aging, the hGH transgenic seminal vesicles exhibited
      massive stromal hyperplasia, whereas the glands from controls and bGH transgenic
      mice did not show this response. Seminal vesicles from old hGH mice presented
      with a marked increase in cell number (DNA content) and a marked decrease in cell
      size and/or glandular secretions (protein/DNA ratio) compared to those from old
      controls and young hGH transgenic mice. Tissue AR content was markedly reduced in
      old hyperplastic hGH seminal vesicles compared to that in seminal vesicles from
      young hGH transgenics, old controls, and old bGH transgenic mice.
      Immunohistochemistry indicated the absence of AR in the proliferating stromal
      cells, whereas acinar epithelial cells showed similar or moderately reduced AR
      staining intensity compared to control seminal vesicles. To examine whether the
      above results may be due to insertional mutagenesis rather than hGH itself, two
      additional GH transgenic lines were examined. Aged transgenic mice expressing bGH
      with an alternate promoter possessed seminal vesicle weights that were not
      different from those of old controls, whereas aged transgenic mice expressing an
      hGH. V gene (variant gene, placental origin) possessed significantly larger
      vesicles than the controls, which further suggests that vesicular hyperplasia is
      specifically related to hGH. To assess androgen responsiveness, aged control and
      hGH transgenic mice were castrated and examined after 15 days. While control
      seminal vesicles significantly decreased in size, glands from transgenic mice did
      not. Regressive changes were observed in the remaining epithelium of hGH
      transgenic mice; however, stromal tissue exhibited no response to androgen
      withdrawal. The present results suggest that the aging-associated seminal vesicle
      hyperplasia in hGH transgenic mice is a result of a massive increase in stromal
      tissue that is low or devoid of AR, suggesting a loss of direct androgen
      regulation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1396346
TI  - Estrogen synthesis by osteoblast cell lines.
AB  - Estrogens play a central role in modulating bone turnover and in the
      postmenopausal female are formed almost exclusively by peripheral conversion of
      sex steroid precursors derived from the adrenals. In this study we have
      demonstrated that three human osteoblastic cell lines [HOS, U20S (HTB96) and
      MG63] possess the enzymes necessary for estrogen synthesis and metabolism.
      Aromatase, estradiol 17 beta-hydroxysteroid dehydrogenase (reductive and
      oxidative) and estrone sulfatase activities were measured in whole cell
      monolayers over a 20 h period by isotopic assay techniques. Significant aromatase
      activity was detected in all three cell lines ranging from 1.8 +/- 0.2 fmol/20
      h/10(6) cells (mean +/- S.D., n = 3) for MG63 cells to 51 +/- 1.5 fmol/20 h/10(6)
      cells for HOS cells. The specific aromatase inhibitor, 4-hydroxyandrostenedione
      (1 mumol/L) completely inhibited aromatase activity in these cells. Two of the
      cell lines, HOS and MG63, had significant estradiol 17 beta-hydroxysteroid
      dehydrogenase activity with oxidative (32.7 +/- 1.9 and 1068.4 +/- 40.2 fmol/20
      h/10(6) cells respectively) predominant over reductive activity (1.6 +/- 0.4 and
      38.7 +/- 1.8 fmol/20 h/10(6) cells). All three cell lines were able to hydrolyse
      estrone sulfate to estrone with activities ranging from 13.3 +/- 1.5 fmol/20
      h/10(6) cells for U20S cells to 482.2 +/- 3.7 fmol/20 h/10(6) cells for MG63
      cells. Since estrogen has been implicated as a critical factor in the modulation
      of bone resorption and formation, the regulation of skeletal estrogen production,
      particularly at the time of the menopause, is likely to be an important mechanism
      by which bone volume is determined in physiological and pathological states.

PMID- 1396347
TI  - Gastrin releasing peptide immunoreactivity is present in ovine amniotic fluid and
      fetal and maternal circulations. MRC Group in Fetal and Neonatal Health and
      Development.
AB  - Using antisera directed towards the C-terminal region of gastrin releasing
      peptide (GRP), significant quantities of GRP-like immunoreactivity (GRPLI) were
      detected in ovine amniotic fluid and in the fetal and maternal circulations. The
      highest GRPLI levels were found in amniotic fluid (2135 +/- 829 fmol/ml, n = 12;
      mean +/- SEM), followed by those in ovine fetal (604 +/- 267 fmol/ml, n = 13) and
      maternal plasma (229 +/- 89 fmol/ml, n = 13). On gel filtration chromatography,
      the predominant GRPLI form in each fluid eluted in an identical position
      consistent with the entity being of apparently larger molecular size than porcine
      GRP1-27. Certain fetal plasma samples contained a second GRPLI peak eluting at
      the void volume. Hence, during ovine pregnancy a GRPLI entity circulates in fetal
      and maternal plasma; the entity is of apparently larger molecular size than GRP1
      27 but contains a structure immunologically indistinguishable from the bioactive
      c-terminal region of GRP1-27. Given the recognized bioactivities of GRP, this
      entity may be an important hormone during ovine fetal life.

PMID- 1396348
TI  - Adrenergic receptors and adenylate cyclase activity in hepatocytes of the
      streptozotocin-diabetic rat.
AB  - Effects of short and long exposure to the diabetic state induced by an injection
      of streptozotocin to young female rats on glucagon- and catecholamine-sensitive
      adenylate cyclase activity and adrenergic receptors of hepatic membranes have
      been studied. The short period of exposure to the diabetic state exhibited an
      increase in the sensitivity of the enzyme to isoproterenol without changes in the
      affinity and the number of beta-adrenergic receptors. The increased response of
      adenylate cyclase activity to isoproterenol was accompanied with a greater GTP
      induced lowering of the affinity to the beta-adrenergic agonist in diabetic
      membranes than in the controls. The chronic diabetic state produced a decrease in
      the adenylate cyclase activity to hormonal or non-hormonal stimuli with a fall in
      the number of alpha- and beta-adrenergic receptors. These results suggest that
      the observed effects of the diabetic state on hormonally sensitive adenylate
      cyclase activities and their receptor binding sites of the hepatic membranes
      would vary depending on the duration and/or severity of the diabetic state
      experimentally induced.

PMID- 1396350
TI  - Altered secretion of corticosteroids and prolactin in adrenal regeneration
      hypertensive rats.
AB  - To assess the possible role of mineralocorticoids in the onset and maintenance of
      hypertension in adrenal regeneration hypertensive (ARH) rats, the change in
      plasma mineralocorticoids, with adrenal regeneration after enucleation in ARH
      rats was investigated and compared with those in unilaterally
      nephroadrenalectomized, 1% saline-fed (UNA) rats, sham-operated, 1% saline-fed
      (1% NaCl) rats and water-fed (water) rats. Plasma aldosterone was determined by
      RIA and the other mineralocorticoids were measured by HPLC. How plasma PRL, a
      marker of central dopaminergic activity, affected aldosterone secretion was
      determined by RIA. In ARH, plasma corticosterone (B), 18-OH-DOC and aldosterone
      levels 2 weeks after operation were as low as 20-30% of corresponding values, but
      the plasma DOC level was almost 100% of the corresponding value in the other
      groups. Four weeks after operation plasma B increased to a level comparable with
      that in the other groups and the plasma aldosterone level remained low. However,
      plasma DOC and 18-OH-DOC levels 4 weeks after operation were as high as 120-200%
      of corresponding values in the other groups. Six weeks after operation, the
      plasma aldosterone level returned to a value comparable with that in UNA and 1%
      NaCl and plasma DOC and 18-OH-DOC levels returned to corresponding values in the
      other groups. The plasma PRL level 4 weeks after operation was significantly
      lower in ARH than in the other groups. These results suggest that transient DOC
      and 18-OH-DOC increases observed in ARH may be important in the onset of
      hypertension, while other factors may be involved in its maintenance and that the
      transient central dopaminergic hyperactivity observed in ARH may be responsible
      for a delayed return from aldosterone deficiency.

PMID- 1396349
TI  - A patient with a prolactinoma associated with an aldosterone producing adrenal
      adenoma: differences in dopaminergic regulation of PRL and aldosterone secretion.
AB  - A patient with a rare combination of prolactinoma and aldosterone producing
      adrenal adenoma (APA) was reported in relation to studies concerning dopaminergic
      regulation of PRL and aldosterone secretion. The patient is a 38-year-old female
      with plasma PRL and aldosterone concentrations (PAC) of 563 ng/ml and 54 ng/dl,
      respectively. A bolus of 10 mg of metoclopramide significantly increased plasma
      PRL in 6 normal subjects and in 4 patients with APA, whereas the responses were
      blunted in 7 patients with prolactinoma and in our patient. The response of
      aldosterone to metoclopramide was less than that of PRL, but similar in all
      studied subjects, indicating that the dopaminergic inhibition of aldosterone
      secretion is less than that of PRL in normal subjects and did not change in
      patients with APA or prolactinoma. Oral administration of 2.5 mg of bromocriptine
      suppressed plasma PRL significantly in all the subjects studied, but did not
      produce any consistent changes in PAC. Discrepancies in the response of PRL and
      aldosterone to metoclopramide and to bromocriptine suggest a difference in the
      dopaminergic regulation of PRL and aldosterone secretion in both normal subjects
      and patients with prolactinoma and APA. It is unlikely that reduced dopaminergic
      inhibition is the basis for hypersecretion of PRL and aldosterone in our patient.

PMID- 1396351
TI  - Recognition of a 56 kDa protein in partially purified rat hepatic nuclear thyroid
      hormone receptor by anti-human c-erb A beta antibody.
AB  - Human beta thyroid hormone receptor (c-erb A beta protein) produced by an
      Escherichia coli expression system was purified by sequential column
      chromatography followed by electroelution from an electrophoresis gel and an
      antibody was prepared. The antibody recognized a 56 kDa protein band in a
      partially purified rat hepatic nuclear thyroid hormone receptor fraction on
      Western blotting. Although multiple bands appeared on Western blotting of crude
      rat hepatic receptor preparations, a 56 kDa band was the most prominent and
      preadsorption of the antibody by purified c-erb A protein resulted in almost
      complete disappearance of the 56 kDa band, indicating that the 56 kDa band was
      formed by a specific antigen-antibody interaction. Furthermore, the 56 kDa
      protein appeared to co-elute with 3, 5, 3'-triiodo-L-thyronine binding activity
      in hydroxylapatite, Sephacryl S-200, and DNA-cellulose column chromatography of
      rat hepatic nuclear receptor, and sequential column purification resulted in
      selective enrichment of the 56 kDa band. These results suggest that the 56 kDa
      protein may be the major component of the rat hepatic thyroid hormone receptor.

PMID- 1396352
TI  - A partial characterization of a Sertoli cell-secreted protein stimulating Leydig
      cell testosterone production.
AB  - To examine whether immature rat Sertoli cells in culture secrete a factor(s)
      which stimulates testosterone production by mature mouse Leydig cells, Sertoli
      cell-enriched cultures were prepared from 3-week-old male rats with trypsin and
      collagenase. Sertoli cells were plated at an initial density of 3-5 x 10(6)
      cells/35 mm well and cultured in 3 ml serum free media supplemented with insulin
      (10 micrograms/ml). Sertoli cell culture medium (SCCM) collected every 3rd day
      was added to Leydig cells (10(6) cells in 1 ml of MEM with 2% steroid-free FCS)
      prepared from 10-week-old mice by mechanical separation and incubated for 3 h at
      34 degrees C. Secreted testosterone was determined by RIA. SCCM 15 times
      concentrated by Amicon YM10 membrane demonstrated a dose-dependent stimulation of
      testosterone production, whereas there was no effect on testosterone secretion
      when Leydig cells were maximally stimulated by LH. Leydig cell stimulating
      activity was retained by both a dialysis membrane with a pore size of 24 A and an
      ultrafiltration membrane with a molecular weight cut-off of 10 kDa. However,
      activity was reduced by heating at 60 degrees C for 30 min and almost lost after
      incubation with 0.1% trypsin for 1 h at 37 degrees C. This activity was not
      retained by means of a Con A-Agarose column and was demonstrated only in break
      through fractions. HPLC gel filtration of a 15 times concentrated SCCM
      preparation on a TSK gel G3000SW revealed Leydig cell-stimulating activity at
      approximately 13 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396353
TI  - Characterization of insulin receptors in the bovine adrenal cortex and medulla.
AB  - In order to identify insulin receptors in the bovine adrenal cortex and medulla,
      we have studied 125I-porcine insulin binding to the membrane preparations from
      the bovine adrenal cortex and medulla. 125I-porcine insulin bound not only to the
      bovine adrenal cortex but to the medulla in time-, temperature-, and pH-dependent
      manners. The maximum levels of 125I-porcine insulin binding in the two tissues
      were observed at 4 degrees C for 24 h of incubation, and its optimum pH ranged
      from 7.6 to 8.0. Under these conditions, at tracer concentration of porcine
      insulin (200 pg/ml), 10.4% and 6.6% of 125I-porcine insulin added to each
      reaction tube bound specifically to 10(5) x g-pellet fractions (microsomal
      membrane) from the cortical tissue (0.3 mg of protein) and from the medullary
      tissue (2 mg of protein), respectively. 125I-porcine insulin binding was observed
      predominantly in the microsomal membrane from the bovine adrenal cortex, and in a
      15,000 x g- pellet fraction (synaptosomal membrane) from the bovine adrenal
      medulla. Scatchard analysis of binding data yielded curvilinear plots in each
      tissue. Analysis of curvilinear plots based on two sites model revealed similar
      affinity constant between the cortex and medulla. Receptor concentration of the
      cortex was several times higher than that of the medulla. In the two bovine
      adrenal tissues, human proinsulin and insulin-like growth factor I (IGF-I) had
      about 1/100 potency compared to porcine insulin in displacing 125I-porcine
      insulin binding. Porcine glucagon added with concentration up to 10(-6) M did not
      inhibit 125I-porcine insulin binding to both the cortex and the medulla.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396354
TI  - Medication of the dental pulp: a review and proposals.
AB  - For years, dentists have desired to treat the intact dental pulp. Since it is
      well-known that many substances, including some drugs, are capable of permeating
      dentin, we believe it is possible to treat certain types of pulpitis by applying
      drugs at the base of cavity preparations. Useful drugs include local anesthetics
      to block pain transmission, glucocorticoids or non-steroidal anti-inflammatory
      agents (NSAIA) to treat inflammation, NSAIA or narcotic analgesics for pain
      control, and antibiotics to treat infection. The literature is reviewed and
      proposals are presented to study medication of the dental pulp.

PMID- 1396355
TI  - Effect of root canal infection and treatment of traumatized primary incisors on
      their permanent successors.
AB  - The purpose of the present retrospective study was to evaluate the effect of
      trauma, root canal infection and treatment of non-vital primary incisors on their
      permanent successors. A total of 117 permanent central incisors were examined
      clinically and radiographically for the presence of discolorations, hypoplasia,
      or disturbances in root development. Of these, 29 were succedaneous to
      traumatized, endodontically involved and treated primary incisors (Group A).
      Another 29 had their traumatized, endodontically involved, primary predecessors
      extracted or left untreated (Group B). The remaining 59 incisors were intact and
      had no history of trauma (Group C). Severe hypoplasia could not be observed in
      any of the teeth, and no disturbances in root development could be disclosed
      radiographically. The incidence of defects in Groups B and C was similar, whereas
      in Group A it was 2 or 3 times higher than in each of the other two groups.
      Despite this fact, root canal treatment of traumatized non-vital primary incisors
      should be considered a treatment option, as premature extraction of a primary
      incisor may lead to speech problems, premature eruption and/or malalignment of
      the permanent successor, or affect the child's self image.

PMID- 1396356
TI  - Effect of trichloracetic acid on the microhardness and surface morphology of
      human dentin and enamel.
AB  - Trichloracetic acid is recommended for the treatment of external cervical root
      resorption. The present study examined the effect of 90% trichloracetic acid on
      the microhardness and surface morphology of human dentin and enamel. Intact
      extracted human teeth were sectioned and embedded in acrylic resin. Each tooth
      was grinded and highly polished exposing a flat surface of dentin and enamel. The
      teeth were treated with 90% trichloracetic acid for 30, 60 and 90 s. Vicker's
      microhardness of the dentin and enamel was assessed for each tooth before and
      after each treatment. In addition the surface morphology of a trichloracetic acid
      treated tooth was examined via SEM. The results showed that 90% trichloracetic
      acid caused a second order type reduction of the microhardness, as well as
      structural changes in both dentin and enamel.

PMID- 1396357
TI  - Mobility and percussion sound of healthy upper incisors and canines.
AB  - In order to evaluate the correlation between mobility and percussion sound, 126
      upper incisors and canines in 21 student volunteers were measured by means of the
      Periotest (Siemens), by evaluating the percussion sound subjectively and by
      analyzing its spectrum. The attenuation time and frequency of the sound were
      measured for each tooth. A logical mobility and percussion sound existed in
      accordance with the sizes of the teeth. Spearman correlation coefficients close
      to 1.00 were noted in individual cases between the Periotest and the three other
      tests describing the percussion sounds.

PMID- 1396358
TI  - Influence of endodontic materials on the bonding of composite resin to dentin.
AB  - We assessed the bond strength of a composite resin to dentin that had been in
      contact with different materials. Flat dentin surfaces in freshly extracted human
      teeth were covered for 15 min or 48 h with a 1-mm layer of a variety of
      materials. The products were mechanically removed and a composite resin
      cylindrical specimen bonded to the dentin surface using the Prisma universal bond
      system. After 7 days immersion at 37 degrees C in water, the tensile bond
      strength was tested. The results were compared with those on dentin surfaces not
      in contact with any endodontic material. Statistical analysis showed that some
      materials (Grossmans Cement, IRM, Maisto's slowly resorbable paste) reduced the
      strength of the bond or even precluded bonding. It is necessary to develop
      techniques that will eliminate this when restoring endodontically treated teeth.

PMID- 1396359
TI  - Treatment of crown fractured incisors with laminate veneer restorations. An
      experimental study.
AB  - A method is described by which crown fractured incisors are restored with cast
      ceramic (Dicor) laminate veneers after initial treatment with either reattachment
      of the original crown fragment with a dentin bonding agent, with a composite
      resin build-up or no treatment (i.e. the veneer alone is used to restore the
      incisal edge). In order to elucidate the effect of the fragment/composite-tooth
      bonding interface on fracture strength of the restored teeth, the fracture
      strengths of the various treatment groups were compared to that of intact teeth
      supplied with Dicor laminate veneers. In an experimental investigation using
      central and lateral incisors from sheep, it was found that fracture strength
      (16.6 +/- 4.2 MPa) equal to that of intact incisors (16.1 +/- 2.6 MPa) could be
      achieved using laminate veneers made of porcelain on fractured teeth whose crown
      fragments were reattached using a dentin bonding agent (5). In the present
      investigation, using the same experimental model but using cast ceramic (Dicor)
      laminate veneers, the fracture strength of the restored incisors was
      significantly increased (21.0 +/- 3.7 MPa), exceeding that of intact teeth. The
      fracture strength of intact teeth was also exceeded in veneered incisors which
      were initially restored with a conventional composite resin build-up (20.2 +/-
      5.6 MPa). However, the greatest fracture strength (28.2 +/- 8.9 MPa) was achieved
      when a Dicor laminate veneer alone was used to restore the fractured incisal
      edge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396360
TI  - Treatment of root fracture with accompanying resorption using cermet cement.
AB  - A method of treating an apical root fracture with accompanying resorption at the
      junction of the fracture fragments using glass-cermet cement is described.
      Endodontically, the material had previously been used for repair of lateral
      resorptive root defects and retrograde root fillings. Complete bone regeneration
      was observed three years post-operatively following treatment of the root
      fracture in the conventional manner. The various advantages of glass-cermet
      cement as a root filling material used in the technique described are discussed.

PMID- 1396361
TI  - Plasmacytoma of anterior maxilla mimicking periapical cyst.
AB  - An unusual case of plasmacytoma mimicking a large periapical cyst in the anterior
      maxilla is described. Of the involved teeth, 22 was discoloured and had an open,
      immature apex, a feature strongly suggestive of the lesion being of pulpal
      origin. The case was treated by a conservative endodontic approach, but failed to
      show any improvement. Apical surgery comprising complete enucleation of the
      cystic lesion and extraction of the involved tooth was carried out. The
      unexpected histopathological finding was a plasmacytoma.

PMID- 1396362
TI  - Efficacy of different irrigation methods and concentrations of root canal
      irrigation solutions on bacteria in the root canal.
AB  - The effectiveness of two different root canal irrigating solutions, each in two
      different concentrations or formulations, with two different irrigation methods
      was compared in vitro by means of bacterial survival determinations. 75 human
      root canals were enlarged, sterilized and inoculated with a mixed culture of
      Escherichia coli and Streptococcus mutans. After inoculation, the root canals
      were irrigated either manually or with an ultrasonic device for equal times (20s)
      with the same amount (5 ml) of sodium hypochlorite (1% and 2%), Fokalhydran I and
      Fokalhydran II. Sodium hypochlorite (1% and 2%) was used in a 1:100 dilution.
      Fokalhydran I and II were used in a 1:10 dilution. In the sodium hypochlorite
      group, the 1% concentration applied with a syringe proved to be most effective
      against Escherichia coli and Streptococcus mutans. The least effective
      concentration and application method against both bacteria species was obtained
      with 2% NaOCL and ultrasonics. Against Escherichia coli and Streptococcus mutans,
      a significantly lower effectiveness was found with 2% NaOCL applied with
      ultrasonics with respect to the rest of the sodium hypochlorite group.
      Fokalhydran I was significantly better than Fokalhydran II against Escherichia
      coli. However, no significant differences could be seen against Streptococcus
      mutans within this group.

PMID- 1396363
TI  - Differentiation of inflammatory bowel conditions by endoscopy and biopsy.

PMID- 1396364
TI  - Crohn's disease of the upper gastrointestinal tract.

PMID- 1396365
TI  - Ultrasonography and endosonography in the diagnosis and management of
      inflammatory bowel disease.

PMID- 1396366
TI  - Infectious agents in inflammatory bowel disease.

PMID- 1396367
TI  - Immunological aspects of inflammatory bowel disease.

PMID- 1396368
TI  - Endoscopic treatment modalities in inflammatory bowel disease.

PMID- 1396369
TI  - Role of endoscopy in the follow-up of inflammatory bowel disease.

PMID- 1396371
TI  - Usefulness and limitations of laparoscopy in the diagnosis of tuberculous
      peritonitis.
AB  - The value of laparoscopy in the diagnosis of tuberculous peritonitis was
      determined in 32 patients diagnosed histologically as having the condition. In 27
      (85%) patients the diagnosis was obtained by laparoscopy combined with peritoneal
      biopsy. In five patients in whom laparoscopy was unsuccessful, the diagnosis was
      established by laparotomy. The visually established diagnosis was unreliable and
      needed histological confirmation. In the ascitic form of tuberculous peritonitis
      laparoscopy was a safe method which enabled a definitive diagnosis. In the
      fibroadhesive form of tuberculous peritonitis laparoscopy was risky and gave
      insufficient information, the diagnosis easily being established by laparotomy.

PMID- 1396370
TI  - A randomized, double-blind, placebo-controlled study to evaluate topical
      anaesthesia of the pharynx in upper gastrointestinal endoscopy.
AB  - Reduction of discomfort during diagnostic upper endoscopy may not be desired by
      patients if the medication has long-lasting and severe after-effects. The present
      study was designed to examine whether topical anaesthesia of the pharynx without
      concomitant sedation is of overall benefit to patients undergoing diagnostic
      upper endoscopy. Two hundred out-patients were randomized to receive in the form
      of a pharyngeal spray either 80-120 mg lidocaine or placebo. Patients assessed
      discomfort on a 100 mm visual analogue scale the day after examination. Patients
      undergoing endoscopy who received lidocaine spray experienced significantly less
      discomfort from the intubation (p = 0.0001), and discomfort induced by the rest
      of the examination was also reduced (p = 0.003). The outcome of the endoscopists'
      assessment was also in favour of lidocaine spray for intubation (p = 0.157) and
      ease of examination (p = 0.0014). The assessment of throat discomfort suffered by
      patients after endoscopy did not differ between the groups. A majority of
      patients, the same proportion in each group, stated they would prefer their next
      endoscopy to be performed with topical anaesthesia.

PMID- 1396372
TI  - Fractals in endoscopy.

PMID- 1396373
TI  - Russell percutaneous endoscopic gastrostomy technique as Sacks-Vine salvage
      option.

PMID- 1396374
TI  - Moschkowitz's disease with gastrointestinal purpura in thalassemia minor.

PMID- 1396375
TI  - A case of Burkitt's lymphoma of the stomach with unusual features.

PMID- 1396376
TI  - First United European Gastroenterology Week. Athens, September 25-30, 1992.
      Abstracts of the ESGE (European Society of Gastrointestinal Endoscopy).

PMID- 1396377
TI  - The OMED data base: standard for nomenclature.

PMID- 1396378
TI  - Modification of the OMED nomenclature: a system approach based on the SISCOPE
      data model.
AB  - The OMED nomenclature represented a turning point in endoscopic computer systems
      by supplying software developers with an internationally recognized scientific
      document on which prototypes could be based. The main pitfalls of the OMED system
      are related to its hierarchical structure, probably not the most effective design
      to represent endoscopic findings. Based on our experience during the development
      of SISCOPE, an integrated data management system for endoscopy, an alternative
      scheme is proposed: Endoscopic descriptions are modeled as a set of objects
      represented by a data structure whose elements are location, morphology,
      associated lesions and hemorrhage. 72 objects appear to be sufficient for an
      accurate representation of all endoscopic scenes and a consistent data model
      could be created with this approach. Efforts should be made to decrease
      redundancy in the OMED nomenclature, but extension to other endoscopic data
      types, such as clinical and pathological diagnosis, is more urgently required.
      Furthermore, if data exchange between systems is desired, the definition of an
      Endoscopy Metafile is an absolute requirement.

PMID- 1396379
TI  - A computerized system for recording data in gastrointestinal endoscopy.
AB  - Over the past five years, the authors have developed a computerized system to
      record and store all the data pertaining to an endoscopic examination of the
      upper digestive tract. The system was designed to permit the easy storage and
      retrieval of data by personnel who lack computer skills and who may only have
      limited typing ability. The system allows for the storage and rapid retrieval of
      patients' individual records, as well as correction and/or deletion of these
      records. The system prints out copies of preliminary endoscopic findings and
      produces a final copy which contains histological and cytological findings. The
      program utilizes a standardized nomenclature, which however permits the
      introduction of each user's code in 16 areas of classification. It is possible to
      analyze statistically and correlate the stored data, permitting easy use for
      clinical studies. The uniformity of the methods for storage of and access to
      patients' records and data, along with the support of a central computer, allows
      multi-centre studies in the field of epidemiology. As of January 1991 30
      endoscopic centres in Portugal have been equipped with this system. Overall the
      experience in these centres has been positive, with excellent or good
      participation in 76.7% of centres.

PMID- 1396380
TI  - System design: which requirements should be met?
AB  - An unsatisfactory start to a computerised endoscopy system is described. Methods
      to combat poor organization are set out. These include defining clinical
      information requirements and integrating these with managerial and computing
      department needs. Decisions need to be taken about the department's ability to
      share information and organization of supervision of the system. Two types of
      database are discussed in relation to their strengths and weaknesses, and
      hardware and software requirements for a typical endoscopy unit are defined.

PMID- 1396381
TI  - Integration into hospital information systems.

PMID- 1396382
TI  - Safety aspects of computerized endoscopic record systems.

PMID- 1396383
TI  - Computerization of endoscopic reports--an ASGE proposal. American Society for
      Gastrointestinal Endoscopy.

PMID- 1396385
TI  - Man--machine--communication.

PMID- 1396384
TI  - Clinical experience with computerised endoscopic record systems in the UK.

PMID- 1396386
TI  - Organization of data input--the importance of rapid/high quality data collection.

PMID- 1396387
TI  - The role of automated speech recognition in endoscopic data collection.
AB  - Speech recognition technology has developed substantially in the past half
      decade. Currently, large vocabulary, speaker independent, discrete recognizers
      are the state-of-the-art. This will change. Moderate sized, continuous
      recognition systems now exist in research settings. However, it is unlikely that
      such systems will be widely available until the mid to late 1990's. The accuracy
      rates of current speech recognition systems are high. Consequently, speech
      accuracy is not the current limiting aspect of using ASR. The limiting aspect of
      using ASR technology is the approach to integrating speech functionality into
      applications. One approach is to use ATNs as models of natural language to
      support both an input strategy and a text generation system. ATNs provide
      approaches to both syntactical correctness and semantic richness. This is an
      approach which plays to the strengths of the discrete nature of current speech
      technology and also provides a methodology for the capture and archiving of
      highly detailed information. The ATN approach avoids the natural language parsing
      problem created by a fully free form dictation interface. Evolving along with the
      underlying speech technology are standards in the definitions and criteria used
      in endoscopic practice. There are clear benefits from standards in this area.
      However, it is likely that this will also take several years and may never yield
      a universally accepted lexicon. Furthermore, there will be user interface
      barriers to surmount in any system attempting to use speech as an input modality.
      Because of the relatively large vocabularies used in medical discourse, the user
      interface will need to be carefully crafted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396388
TI  - Knowledge-based user guidance for endoscopic database systems.

PMID- 1396389
TI  - Current developments in electronic endoscopy.

PMID- 1396390
TI  - Image manipulation: digital versus analog.
AB  - A conceptual difference between "analog" and "digital" digitizing is reviewed.
      Analog and digital type image filing systems are discussed from a comparative
      point of view: The analog type is advantageous in the number of recordable
      images, the recording and reproducing speed, and the ability to record a moving
      picture, while the digital type, in which images are digitized when recorded, is
      capable of reproducing a higher quality image that does not deteriorate when
      copied repeatedly. It has the advantage that it easily interfaces with computer
      systems. As technology developed to compensate for the drawbacks of the digital
      type systems, image data compression was introduced. Finally, the possibility for
      recording a moving picture in a digital type system is discussed.

PMID- 1396391
TI  - Storage of endoscopic images.

PMID- 1396392
TI  - Image management: the viewpoint of the clinician.

PMID- 1396393
TI  - Endoscopic image manipulation: state of the art.
AB  - Fundamental techniques and commonly employed algorithms for image manipulation of
      endoscopic images were reviewed, but only in a few instances was any novel
      information obtained. New software was recently developed for medium-frequency
      band enhancement: From the correlation distribution of image data in the RGB
      color space (distribution 1), only those data components depicting the fine
      structure patterns were extracted. The correlation distribution of the latter
      components was subsequently studied in the same space (distribution 2); the
      original image data were so processed that distribution 1 would be enhanced along
      the axis of greatest variation seen in distribution 2. This algorithm of image
      processing was successful in detecting minute surface structures of the mucosa
      hidden by the overlying mucus in the original images. It seems to be the first
      successful algorithm of image processing that obtained specific effects of
      enhancement without simultaneous noise enhancement.

PMID- 1396394
TI  - Computer-assisted two-dimensional analysis of gastric mucosal hemoglobin
      distribution using electronic endoscopy.
AB  - An electronic endoscope was modified to assess the imaging of two-dimensional
      distribution of gastrointestinal mucosal hemoglobin with the aid of a computer
      and image analyzing system. The band-pass filters ranging from 530-470 nm (G'),
      and 770-830 nm (IR) replaced ordinary filters in a conventional electronic
      endoscope (Olympus V-10 or EVIS-200). As the hemoglobin is the most abundant
      biological pigment in the gastrointestinal mucosa absorbing the green light with
      little absorption in the infrared region, we used the algorithm of 32
      [log2(Vir/Vg)] as a reflection of hemoglobin content in the surface mucosa. The
      algorithm had a good correlation with the spectrophotometrically measured
      hemoglobin concentration. The mucosal distribution of hemoglobin was displayed in
      patients with gastric ulcer. In conclusion, the computer and image analyzing
      system were successfully applied in an attempt to determine gastric mucosal
      hemoglobin content and its distribution. The possible applications of computers
      in endoscopic image analysis are discussed.

PMID- 1396395
TI  - Quality assurance by computerized endoscopy record systems.
AB  - Quality assurance in gastrointestinal endoscopy, as a crucial diagnostic and
      therapeutic process in medical care, has become a matter of increasing interest.
      However, concrete measures and standards are still lacking. Quality assurance as
      "continuous improvement" and "improvement by inspection" are discussed. Examples
      for clinical measures in the fields of indication for endoscopy, accuracy to the
      diagnostic test, thoroughness of the procedure and assessment of complications
      are given, and educational problems are discussed. Such structural problems of
      quality assurance as handling of a vast amount of data and assessment of late
      complications by follow-up information are addressed. Electronic data processing
      seems to be the most economic way to solve these problems. Requirements to data
      processing in the view of quality assurance are defined. Transferral of data from
      other departments within a hospital information system is necessary for the
      assessment of long-term follow-up. Different methods of communication within a
      hospital information system are discussed.

PMID- 1396396
TI  - Computers in endoscopy--scientific aspects and research.

PMID- 1396397
TI  - Computer assisted training in endoscopy (C.A.T.E.): from a simulator to a
      learning station.

PMID- 1396398
TI  - Robotics interactive endoscopy simulation of ERCP/sphincterotomy and EGD.

PMID- 1396399
TI  - The future of endoscopy simulation: a Duke perspective.

PMID- 1396400
TI  - Computer simulation for teaching endoscopic procedures.

PMID- 1396401
TI  - Overview of interactive endoscopy simulators.

PMID- 1396402
TI  - Contrast variation studies of clathrin coated vesicles by small-angle neutron
      scattering.
AB  - Structural information on clathrin coated vesicles has been obtained by small
      angle neutron scattering using contrast variation. A characteristic peak in the
      neutron scattering profile, which is apparent in 75% D2O, as well as in H2O,
      disappears when contrast matching the protein component of the coated vesicles in
      42% D2O. Neutron, as well as dynamic, light scattering give a coated vesicle size
      of about 900 A in H2O and D2O, but for neutron scattering the diameter decreases
      when matching out the protein coat of the clathrin coated vesicles. From the
      match point for the clathrin coated vesicles it is demonstrated that the clathrin
      cages do contain internal membrane. The mass of 34 MD and composition of 75%
      protein and 25% lipid found from the analysis of the small-angle scattering data
      are both in good agreement with the values reported in the literature. Electron
      microscopy gives an average outer diameter of 880 A for the coated vesicles and
      an average diameter of 460 A for the vesicle itself.

PMID- 1396404
TI  - Influence of protein dynamics on the metal-sites of ovotransferrin.
AB  - Using the perturbed angular correlations (PAC) technique, the formation of
      hafnium-ovotransferrin complexes has been studied. Two binding configurations at
      each of the two specific binding-sites of the protein have been observed. They
      are characterized by well-defined electric quadrupole frequencies. Information
      about the dynamics of the protein was derived from temperature dependent
      measurements of the relaxation constant. The well-resolved spectra taken with
      fast BaF2-detectors allow a precise determination of the relaxation behaviour of
      the protein. The results are compared with the predictions from a hydrodynamic
      model for the reorientation of macromolecules. Thus the hydrodynamic volume of
      ovotransferrin and its N-terminal half-molecule were determined. The
      ovotransferrin volume is in agreement with a value derived for human serum
      transferrin from small angle neutron scattering. From experiments with
      immobilized protein material there is evidence for internal protein dynamics
      which is probed by the Hf-ion bound to the specific metal-sites.

PMID- 1396403
TI  - A theoretical study of glucosamine synthase. II. Combined quantum and molecular
      mechanics simulation of sulfhydryl attack on the carboxyamide group.
AB  - Continuing our theoretical studies of glucosamine synthase catalysis, we have
      carried out MNDO and ab initio calculations of the first stage of the reaction,
      which involves the attack of a cysteine thiol group from the enzyme active site
      on the side chain carboxyamide group of glutamine, producing ammonia and
      thioester. The reactants were modelled by methyl mercaptate and acetamide,
      respectively. For two considered mechanisms of the reaction the energy surfaces
      were evaluated. Mechanism I, proposed by Chmara et al. (1985) involves the
      nucleophilic attack of a deprotonated thiol group on the carbonyl carbon atom.
      Mechanism II, postulated in our previous work (Tempczyk et al. 1989), assumes the
      concerted binding of the mercaptate sulphur to the carbonyl carbon and the
      sulfhydryl hydrogen to the amide nitrogen with simultaneous breaking of the S-H
      bond. The energy surface of mechanism I shows no minimum on the approach of the
      mercaptide anion towards the carbonyl carbon, which is also consistent with ab
      initio calculations in a 4-31 G basis set. Therefore, mechanism I seems to be
      unlikely. The same analysis of mechanism II shows that it leads to the desired
      products: methyl thioacetate and ammonia. The presence of a sulfhydryl hydrogen
      causes apparent pyramidicity of the amido nitrogen and lengthening of the C-N
      bond in the transition state, making conditions for the release of the ammonia
      molecule. The MNDO calculated energy barrier of the reaction is 50.1 kcal/mol and
      the approximate 4-31 G ab initio barrier (at the MNDO geometries of the substrate
      complex and the transition state) is 63 kcal/mol.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1396405
TI  - Structural organization of guanosine derivatives in dilute solutions: small angle
      neutron scattering analysis.
AB  - Guanosine derivatives, dissolved in water, can form cholesteric and hexagonal
      mesophases. The common structural unit is a chiral rod-shaped aggregate
      consisting of a stack of Hoogsten-bonded guanosine tetrameric disks. In order to
      elucidate the self-association process, we decided to investigate, by small-angle
      neutron scattering, the structural properties of d(pG), d(GpG), d(GpGpG),
      d(GpGpGpG) and d(GpGpGpG pGpG) derivatives in very dilute solutions. Under our
      experimental conditions only d(pG) seems not to form detectable particles. On the
      other hand, the results for the other derivatives indicate that cylindrical
      aggregates, having a 10 A cross-section gyration radius and a length of about 70
      A, exist in the isotropic phase. According to the structure of the hexagonal and
      cholesteric phases, we fitted the experimental data by using a model of rod
      shaped aggregates formed by stacking about 18 to 20 guanosine tetramers.
      Moreover, from the measurement of the concentration of scattering particles, we
      deduced that guanosine derivatives are only partially aggregated, depending on
      their ability to form mesophases.

PMID- 1396406
TI  - Kinetics of the reconstitution of hemoglobin from semihemoglobins alpha and beta
      with heme.
AB  - Kinetics of the reconstitution of hemoglobin from semihemoglobins alpha and beta
      with hemin dicyanide have been investigated using three kinds of stopped-flow
      technique (Soret absorption, fluorescence quenching of tryptophan, and Soret CD).
      The semihemoglobins alpha and beta are occupied by heme in the alpha and beta
      chains, respectively, the other chain being heme-free. Based on the kinetic
      results, the following scheme for the reconstitution is proposed; First, hemin
      dicyanide enters the pocket-like site of the apo chains. Second, in
      semihemoglobin alpha, the CN-ligand in the fifth coordination position of iron is
      replaced by the imidazole ring of the proximal His immediately after the heme
      insertion. In contrast, semihemoglobin beta changes its conformation after the
      heme insertion, and this is followed by the ligand replacement. Finally, the
      partial structure changes induced by the ligand replacement propagate onto the
      whole molecule and the final conformation is attained. The results indicate that
      semihemoglobin alpha retains a more rigid and organized structure, and more
      closely approaches its final structure than does semihemoglobin beta.

PMID- 1396407
TI  - The effect of phloretin on single potassium channels in myelinated nerve.
AB  - The effect of phloretin, a dipolar organic compound, on single potassium channel
      currents of myelinated nerve fibres of Xenopus laevis has been investigated,
      using inside-out patches prepared by the method of Jonas et al. (1989). The I
      channel, a potential dependent K channel with intermediate deactivation kinetics,
      was reversibly blocked by 20 microM phloretin applied on the inside; the block
      was strongest at negative membrane potentials and less pronounced at positive
      potentials. Phloretin shifted the curve relating open probability to membrane
      potential towards more positive potentials and reduced its slope and maximum.
      This confirms previous findings on the effect of phloretin on the voltage
      dependence of the fast macroscopic K conductance. Single channel conductance and
      deactivation kinetics were not altered by phloretin.

PMID- 1396408
TI  - Eosinophils and major basic protein damage but do not detach human amniotic
      epithelial cells.
AB  - Damage and detachment of epithelial cells is thought to contribute to the
      pathologenesis of asthma. Both eosinophils and neutrophils are found in asthmatic
      airways and several studies have suggested that eosinophils may be responsible
      for the epithelial cell detachment of asthma. To compare the capacity of purified
      human eosinophils and neutrophils to mediate epithelial cell detachment, we
      utilized a human amniotic epithelial cell-basement membrane model that we have
      recently described. Activated eosinophils induced little detachment at 4 h (less
      than 10% detachment), which contrasted with that seen with equivalent numbers of
      identically handled neutrophils (29 +/- 6% detachment, p less than .05). In
      contrast, eosinophils did induce damage to epithelial cells to an extent similar
      to neutrophils when assessed using a 51Cr release assay (17 +/- 6% and 18 +/- 9%
      release of 51Cr, respectively). When purified preparations of the major
      eosinophil-derived protein major basic protein (MBP) were studied, similar
      effects on epithelial cells were observed, i.e., damage (77 +/- 13% release of
      51Cr) without detachment (less than 5% cell detachment). These data suggest that
      neutrophils are more effective in inducing detachment of human epithelial cells,
      whereas both eosinophils and neutrophils damage human epithelial cells.

PMID- 1396409
TI  - Passage of aerosolized BSA and the nona-peptide dDAVP via the respiratory tract
      in young and adult rats.
AB  - The passage of the protein marker, bovine serum albumin (BSA, MW = 67,000), and
      the nona-peptide, 1-deaminocysteine-8-D-arginine vasopressin (dDAVP, MW = 1067),
      from the respiratory tract into the blood when applied as an aerosol with a MMAD
      of 1.7 microns was studied in 14-, 30-, and 100-120-day-old (adult) healthy rats
      and in adult rats with lung injury. In blood serum of adult rats the levels of
      immunoreactive BSA reached its maximum 16-24 h after a 1-h aerosol exposure with
      a calculated total passage of 6.4 +/- 1.8% of the given dose. dDAVP serum levels
      measured by RIA peaked after 0.5-1 h, giving a total passage of 84.3 +/- 12.9%.
      With increasing exposure periods from 0.5 to 3 h, which thereby increased the
      lung burden, the serum levels of BSA and dDAVP increased linearly indicating
      passive transepithelial transport processes for both molecules. For the young
      rats, similar serum level-time curves were obtained like those of the adult, with
      similar total passages of BSA, 4.6 +/- 0.8% for the 14-day-old rats and 5.2 +/-
      1.6% for the 30-day-old rats. For dDAVP the total passage was significantly lower
      in both the 14-day-old rats, 40.9 +/- 12.1%, and the 30-day-old rats, 16.7 +/-
      6.1% (p less than .05), as compared to the adult rats. Acute lung inflammation
      induced in rats by intratracheal instillation of 5 mg ferritin/kg body wt prior
      to a 1-h marker aerosol exposure increased the passage of BSA (58.7 +/- 18.8%, p
      less than .05), while the dDAVP passage was less affected (99.2 +/- 25.2%, p
      greater than .05) as compared to the healthy adult rats. The results indicate
      that after aerosol exposure the total passage of dDAVP over the respiratory tract
      was higher than that of the macromolecule BSA, the passage appeared to increase
      with the maturity of the rats and by inflammatory changes in the lung tissue.

PMID- 1396410
TI  - Aerosol tracer study of gas convective transport to 0.1-cm airways by high
      frequency ventilation in a human lung airway cast.
AB  - A cast of human tracheobronchial airways, which is complete to airways less than
      0.1 cm in diameter, was employed for experimental studies of gas convective
      transport by high-frequency ventilation (HFV). The cast was ventilated with gases
      of different kinematic viscosity (He, air, and SF6) and tidal volumes of 10-60
      mL. The convective transport through the cast was followed by labeling the tidal
      volume with 0.5-micron aerosol particles. Such particles undergo little diffusion
      and have a short relaxation time and, therefore, can serve as tracers of stream
      flow. The time of arrival of particles transported to isolated peripheral
      segments of the cast during HFV was measured with an optical particle counter at
      various oscillatory tidal volumes and frequencies. Distally directed particle
      transport was found to be substantial in He and air, but weak in SF6. The extent
      of transport increased with increasing tidal volume. These results provide
      evidence for a distally directed axial flow during quasi-steady-state tidal
      breathing of lung airways over a wide range of frequency. This superimposed
      distal flow along the axial core is consistent with (1) the demonstrated efficacy
      of O2-CO2 exchange during HFV, and (2) concentrations of particles deposited on
      bifurcations of alveolar ducts as observed during normal breathing in small
      animal inhalation studies.

PMID- 1396411
TI  - Hydrogen peroxide release from alveolar macrophages and alveolar type II cells
      during adaptation to hyperoxia in vivo.
AB  - The effect of hyperoxia (1-14 days, 85% O2) on rat alveolar macrophage and
      alveolar type II cell oxidant and antioxidant characteristics was investigated.
      Unstimulated control macrophages (2 h ex vivo) released hydrogen peroxide at a
      rate of 3.5 +/- 1.3 nmol/min mg protein-1, which was a cyanide-sensitive process.
      H2O2 release from alveolar macrophages decreased slightly but not significantly
      after 1 day in hyperoxia and increased significantly after 3 days (180%, p less
      than .05) and 14 days (380%, p less than .01). When H2O2 release was expressed as
      nmol from total macrophages per animal, the increase after 14 days in hyperoxia
      was 760%. H2O2 generation by hyperoxic macrophages was cyanide resistant,
      indicating the involvement of active NADPH oxidase. In both control and hyperoxic
      macrophages H2O2 release could be significantly stimulated with phorbol myristate
      acetate (PMA). Comparisons of H2O2 release by freshly isolated alveolar
      macrophages and alveolar type II cells must be cautiously interpreted because
      some cell functions may change during the isolation procedure. Freshly isolated
      (6 h ex vivo) control alveolar type II cells were found to generate H2O2 at a
      rate of 0.26 +/- 0.05 nmol/min mg protein-1. In type II cells H2O2 release,
      calculated as nmol/mg protein, decreased during the first 7 days of hyperoxia to
      10% (p less than .01) of the control value and then returned back up to the
      control level after 14 days. A similar decrease was observed if H2O2 release was
      calculated as nmol/cell number. H2O2 release from control and hyperoxic type II
      cells was cyanide sensitive. The decrease in H2O2 release in type II cells was
      associated with cell membrane injury (as assessed by electron microscopy), while
      biochemical markers of cellular injury (trypan blue exclusion and cellular high
      energy phosphates ATP, ADP) were unchanged. The ability of type II cells to
      scavenge extracellular H2O2 did not change in acute hyperoxia, but it increased
      significantly during the second week in hyperoxia. These results indicate that
      macrophages but not type II cells are stimulated to produce H2O2 during prolonged
      exposure to hyperoxia.

PMID- 1396412
TI  - Effects of food deprivation on experimental emphysema in obese rats.
AB  - Obese male rats, with an average body weight of 530 g (approximately 30 weeks
      old), received either pancreatic elastase (75 microns/100 g) or saline
      intratracheally and were divided into fed and starved groups. Starved rats were
      given one-third of their measured daily food consumption. All groups were studied
      4 weeks after the initiation of starvation. In both elastase and saline exposed
      rats, the saline volume-pressure curves expressed as a percentage of maximal lung
      volume were similar in fed and starved groups. Mean linear intercept (Lm) and
      alveolar surface area (Sa) were not different between the control-fed and the
      control-starved rats. Lm was similar but Sa was significantly smaller in the
      elastase-starved compared with the elastase-fed groups. It is concluded that, in
      contrast to the aggravating affects of weight loss on experimental emphysema in
      adult nonobese rats, food restriction does not affect elastase-induced injury
      significantly in obese animals.

PMID- 1396413
TI  - Mineral particles in the human bronchial mucosa and lung parenchyma. II.
      Cigarette smokers without emphysema.
AB  - The effects of cigarette smoke on the microanatomic deposition and retention
      pattern of exogenous mineral particles is unknown. To determine how cigarette
      smoke affects long-term particle retention in those with minimal smoke-related
      disease, we selected autopsy lungs from ten smokers without evidence of emphysema
      at autopsy, and used analytical electron microscopy to examine exogenous mineral
      particle concentration in the mucosa of seven different bronchi of varying sizes
      and four parenchymal sites fed by those bronchi. These data were compared with
      values from twelve lifetime nonsmokers. Overall, total mean particle burden in
      the parenchyma in the smokers and nonsmokers was similar, but there was a
      markedly decreased particle load retained in the smokers' airways. The consistent
      increase in particle burden seen in nonsmokers as airways became narrower and
      more distant from the carina was lost in many, but not all, of the smokers,
      especially for particles larger than 1 micron, and this effect did not appear to
      depend on amount of smoking. Rare polonium particles were found but were too
      sparse to use as a smoke distribution marker. However, calcium-containing
      particles, previously suggested by us to represent calcium carbonate actually
      derived from the smoke, were present in greatest concentration in the larger
      airways and distal parenchyma. These observations indicate the following in
      smokers without parenchymal smoke-induced structural damage: (1) Overall,
      cigarette smoking disrupts the normal retention (? deposition) pattern of
      particles in the airways. (2) Cigarette smoking leads to markedly decreased long
      term retention of exogenous mineral particles in the airways without
      significantly affecting overall tissue particle retention. (3) The distribution
      of calcium particles in the airways and parenchyma in smokers is similar to that
      predicted in a recently published model of smoke particle deposition, and further
      supports the idea that calcium-containing particles can be used as a direct
      tracer of smoke particle deposition. In the present study this distribution
      indicates that the large airways and parenchyma receive the greatest smoke
      deposition. (4) Within the group of smokers, some people appear resistant to the
      disruptive effects of smoke on particle retention patterns, whereas other people
      smoking comparable amounts show markedly abnormal retention patterns. The latter
      may have unusual sensitivity to cigarette smoke and perhaps susceptibility to
      smoke-induced diseases.

PMID- 1396414
TI  - Inhibitory action of tetrandrine on macrophage production of interleukin-1 (IL-1)
      like activity and thymocyte proliferation.
AB  - Tetrandrine is a bisbenzylisoquinoline alkaloid which has been shown to exhibit
      antifibrotic activity against silicosis. Tetrandrine is characterized by its
      strong binding to alveolar macrophages and inhibition of particle-induced
      respiratory burst activity in these phagocytes. In contrast, tubocurine and
      tubocurarine are structurally similar to tetrandrine but exhibit little effect on
      fibrosis or activation of alveolar macrophages. The objective of the present
      study was to test the effect of tetrandrine on macrophage production of monokines
      in response to occupational dusts, and to determine tetrandrine's effect on
      monokine-medicated cell growth using a mouse thymocyte proliferation assay and
      lipopolysaccharide (LPS) as a positive control. Stimulation of alveolar
      macrophages by respirable silica dust resulted in a release of monokines which
      caused a fourfold increase in thymocyte proliferation. Coal dust, on the other
      hand, had no effect on macrophage production of this cytokine. Tetrandrine was
      found to exhibit a dose-dependent inhibition of monokine release from both silica
      and LPS-stimulated alveolar macrophages. In experiments where thymocytes were
      directly treated with tetrandrine, a dose-dependent inhibition of thymocyte
      proliferation was noted with both interleukin-1-(IL-1) specific and nonspecific
      mitogenic (concanavalin A) actions. In contrast to the inhibitory potency of
      tetrandrine, tubocurarine was found to have no effect on either the production of
      monokines by LPS-stimulated alveolar macrophages or IL-1-mediated thymocyte
      proliferation. These results provide a correlation between the antifibrotic
      effect of tetrandrine and inhibition of macrophage activation.

PMID- 1396415
TI  - Changes in the carbohydrate content of airway epithelium induced by human
      neutrophil elastase in the hamster.
AB  - Hamster airway epithelial secretory cells were investigated by light and electron
      microscopic cytochemistry to study possible changes in their carbohydrate content
      induced by human neutrophil elastase (HNE), an agent known to cause replacement
      of Clara cells by mucous cells in hamster bronchi. Characterization of secretory
      cell carbohydrates by the AB/PAS, PA-TCH-SP, HID-TCH-SP, and LID-TCH-SP sequences
      indicated the existence of periodate-reactive acidic glycoconjugates, but the
      absence of sulfated or carboxylated glycoconjugates in both treated and control
      animals. Differences were seen in the quality and quantity of historeactive
      carbohydrates throughout various regions in the lower respiratory tract. This was
      especially evident in the HNE-treated animals. It is concluded that the HNE
      induced expression of the mucous cell phenotype is associated with an increase in
      the amount of neutral and acidic nonsulfated and noncarboxylated polysaccharides
      stored in the secretory granules of these cells.

PMID- 1396416
TI  - Studies on pH regulatory mechanisms in cultured astrocytes of DBA and C57 mice.
AB  - pH regulatory mechanisms in primary cultures of astrocytes from the cerebral
      cortex of neonatal audiogenic-seizure-susceptible DBA/2J (DBA) and genetically
      controlled C57BL/6J (C57) mice were studied with [14C]dimethyloxazolidine-2-4
      dione (DMO) and [3H]-methyl-D-glucose (MDG). Effects of changing the
      concentration of Na+, K+, HCO3- or Cl- in medium, and/or of different transport
      blockers and metabolite inhibitor on intracellular pH (pHi) of cultured
      astrocytes were also studied. In nominal HCO3(-)-free HEPES-buffered Hanks'
      balanced salt solution (HEPES HBSS), when the pH of medium (pHo) was maintained
      at 7.4, the steady-state pHi of cultured astrocytes from DBA mice was 6.98 +/-
      0.03, and that from C57 mice was 7.01 +/- 0.03. When the cells were incubated in
      HBSS containing 25 mM HCO3- and equilibrated with 5% CO2 (HCO3- HBSS, pHo = 7.4),
      pHi of both DBA and C57 astrocytes was approximately 0.1-0.15 pH units higher
      than that in HEPES HBSS. Reducing the pH or the Na+ concentration in media (pHo,
      [Na+]o) of either HEPES HBSS or HCO3- HBSS, pHi of both DBA and C57 astrocytes
      decreased markedly (0.25-0.45 pH units lower than the controls). The decrease in
      pHi was greater in HEPES HBSS than in HCO3- HBSS. Reducing the Cl- concentration
      ([Cl-]o) in either HEPES or HCO3- HBSS, pHi of astrocytes increased by 0.05-0.1
      pH units. Increasing the K+ concentration ([K+]o) of or adding Ba2+ to the media
      increased the pHi of both DBA and C57 astrocytes accordingly. SITS, an anion
      transport inhibitor, decreased the pHi of both DBA and C57 astrocytes in HCO3-
      HBSS but not in HEPES HBSS. It enhanced the response of pHi to reduction in pHo.
      Amiloride, a Na(+)-H+ exchange inhibitor, decreased the pHi of both DBA and C57
      astrocytes more in HEPES HBSS than in HCO3- HBSS. It enhanced the response of pHi
      to reduction in pHo and [Na+]o. Ouabain, an Na+,K(+)-ATPase inhibitor, decreased
      the pHi of cultured astrocytes in HEPES HBSS, but not in HCO3- HBSS. It also
      enhanced the response of pHi to changing pHo and [Na+]o in HEPES HBSS.
      Acetazolamide, a carbonic anhydrase inhibitor, decreased the pHi of astrocytes in
      both HEPES and HCO3- HBSS. Both bumetanide, an Na+,K+/Cl- cotransport blocker,
      and KCN, a metabolic inhibitor, produced no significant effect on the steady
      state pHi or the response of pHi to changing ionic concentration in media in both
      DBA and C57 astrocytes.

PMID- 1396417
TI  - Monaural audiogenic seizures: evidence for control by parallel processes.
AB  - SJL/J mice were binaurally sensitized and monaurally tested for susceptibility to
      sound-induced seizure. Most control subjects exhibited the expected biphasic
      pattern of running. In mice in the experimental groups, the acoustic stimulation
      was interrupted for less than 20 s at the conclusion of the initial burst of
      running. During this quiet period, the side of the blocked ear was reversed for
      some mice. These mice had an independent biphasic seizure when acoustic
      stimulation was reintroduced, indicating that the biphasic seizure progression
      characteristic of monaural testing is the result of a lateralized process. We
      conclude that the locus of this process is probably at the level of the inferior
      colliculus (IC).

PMID- 1396418
TI  - Ontogeny of feline temporal lobe epilepsy, II: Stability of spontaneous sleep
      epilepsy in amygdala-kindled kittens.
AB  - We previously described a model of spontaneous "sleep epilepsy" in kindled
      kittens with temporal lobe epilepsy (TLE). We now describe the postkindling
      course of this model from preadolescence to maturity and suggest pathophysiologic
      mechanisms. Spontaneous epilepsy, particularly generalized tonic-clonic
      convulsions (GTCs), developed 1h to 4 months after amygdala kindling and
      persisted to adulthood. At first, GTCs were detected only in sleep; later,
      convulsions also occurred during wakefulness. Two factors were consistently
      associated with the sequential onset of sleep and waking GTCs: seizure clusters
      and anatomic seizure localization. (1) Seizure clusters. Cats with infrequent or
      unclustered GTCs continued to exhibit "sleep epilepsy," defined by convulsions
      occurring exclusively during sleep. In contrast, cats with frequent seizure
      clusters developed recurrent or terminal convulsive status in conjunction with
      GTCs during waking and sleep. Severe seizure manifestations therefore appeared to
      contribute to the dissociation of convulsions from the sleep-wake cycle. (2)
      Anatomical seizure localization. Focal seizure origin appeared to differentiate
      sleep from waking GTCs. Onset during sleep was first recorded in the kindled
      amygdala, whereas onset during waking was initially detected outside the temporal
      lobe. Findings thus suggest secondary "kindling" of multifocal epilepsy.
      Secondary epileptogenesis is consistent with "transsynaptic" kindling effects.
      This phenomenon is defined in mature animals by rapid secondary site kindling
      (transfer) and subtle morphologic changes distal to the stimulating electrode.
      Transfer may be accentuated by youth, because kittens developed spontaneous
      seizure foci in previously unstimulated tissue. Moreover, multifocal interactions
      and diffuse cell loss were implicated as possible mechanisms. Collectively, the
      findings indicate complications with early onset TLE in kindled cats. Onset
      during youth can have an unfavorable prognosis, reflected by recurrent status
      epilepticus and multifocal epilepsy with convulsions distributed throughout the
      sleep-wake cycle.

PMID- 1396420
TI  - Video-EEG analysis of drop seizures in myoclonic astatic epilepsy of early
      childhood (Doose syndrome).
AB  - We studied 36 drop seizures in 5 patients with myoclonic astatic epilepsy of
      early childhood (MAEE) with simultaneous split-screen video recording and
      polygraph. Sixteen were falling attacks and 20 were either less severe attacks
      exhibiting only deep head nodding or seizures equivalent to drop attacks in terms
      of ictal pattern but recorded in the supine position. All seizures except those
      that occurred in patients in the supine position showed sudden momentary head
      dropping or collapse of the whole body downward. Recovery to the preictal
      position was observed in 0.3-1 s. As a result of carefully repeated observations,
      the 36 seizures were classified as myoclonic flexor type in 9, myoclonic atonic
      type in 2, and atonic type, with and without transient preceding symptoms in the
      remaining 25. The MF seizure was characterized by sudden forward flexion of the
      head and trunk as well as both arms, which caused the patient to fall. In the
      myoclonic atonic seizure, patients showed brief myoclonic flexor spasms,
      immediately followed by atonic falling. The AT seizure showed abrupt atonic
      falling, with and without transient preceding facial expression change and/or
      twitching of extremities. The ictal EEGs of all 36 seizures exhibited generalized
      bilaterally synchronous single or multiple spike(s) and wave discharges. Atonic
      drop attacks appear to be a common cause of ictal epileptic falling in MAEE.

PMID- 1396419
TI  - Sleep microstructure and EEG epileptiform activity in patients with juvenile
      myoclonic epilepsy.
AB  - Clinical and EEG manifestations of juvenile myoclonic epilepsy (JME) occur in a
      strict relationship to the sleep-wake cycle, particularly to transition phases
      (awakening, falling asleep, afternoon relaxation after work). JME manifestations
      are deactivated during sleep. Because arousal fluctuations during NREM sleep may
      be controlled by the same neurophysiologic mechanisms regulating awakening, we
      studied the relationship between the cyclic alternating pattern (CAP) and JME
      manifestations. All-night polysomnographic recordings of 10 JME patients were
      analyzed for variations of epileptiform EEG abnormalities in relation to sleep
      stages and to different microstructural variables (NCAP, CAP, phases A and B).
      CAP rates (ratio between total CAP duration and total NREM sleep duration) were
      also calculated. Average CAP rate was 46.70%, significantly higher than that
      (23%) of an age-matched control group. Macrostructural analysis showed only a
      trend toward a slight predominance of EEG epileptiform activity during slow wave
      sleep but no significant correlation between spiking rates and sleep stages.
      Microstructural analysis confirmed the CAP modulation of EEG epileptiform
      activity, with maximum appearance of epileptiform abnormalities during phase A
      CAP (normalized spiking rate = 4.00 +/- 0.98) and strong inhibition during phase
      B (0.06 +/- 00.6). Intermediate values were noted during NCAP (0.54 +/- 0.27). No
      correlation was noted between spiking rates during NREM sleep and CAP rates,
      possibly indicating that in JME patients the increased CAP rate may be partially
      independent of epileptiform EEG activity. Our data suggest that in JME patients
      CAP may be a neurophysiologic oscillator organizing expression of the
      epileptiform discharges independent of the tendency of the individual patient to
      produce epileptiform EEG discharges.

PMID- 1396421
TI  - Possible association of juvenile myoclonic epilepsy with HLA-DRw6.
AB  - Juvenile myoclonic epilepsy (JME) is a clearly defined subform of idiopathic
      generalized epilepsy with a high aggregation of epilepsy in family members. With
      the HLA-system used as a genetic marker, a linkage between JME and the HLA region
      was demonstrated. Linkage with the HLA region suggests that JME may be associated
      with an HLA-antigen. An association could indicate that the gene lies in the HLA
      region and is in linkage disequilibrium with one of the HLA-antigens. Eighty
      eight unrelated patients with JME were typed for the HLA-A and HLA-B locus, 77
      were typed for the HLA-C locus, and 76 were typed for the DR locus. The antigen
      frequency was compared with those of healthy blood donors. The highest difference
      was noted in the frequency of DRw6 (39.5% in patients vs. 22.1% in controls).
      This weak association is open to question because DRw6 is known to split into
      DRw13 and DRw14.

PMID- 1396422
TI  - Neonatal hyperekplexia: a case report.
AB  - We report the case of a baby with transient generalized stiffness noticeable from
      the first days of life, hyperreflexia, massive jerks in response to sudden
      tactile and acoustic stimuli, and long-lasting myoclonic jerks closely resembling
      epileptic seizures. The father and paternal grandfather both had hyperekplexia.
      At age 3 years, the child had normal psychomotor development and persistent
      abnormal startle response to unexpected sounds or touch.

PMID- 1396423
TI  - Late-onset epilepsy and diffuse cryptogenous cerebral atrophy.
AB  - Diffuse cerebral atrophy (CA), a frequent computed tomography (CT) finding in
      late-onset epilepsy, is sometimes of unknown origin or cryptogenous (CCA). From a
      series of 228 patients with late-onset epilepsy with diffuse CA, we excluded
      patients with a presumed etiology. The remaining 73 (36.8%) patients were studied
      for a mean of 7.2 years; 15.1% had a family history of epilepsy. CCA was cortical
      in 50.7%, subcortical in 6.8%, and corticosubcortical in 42.5%. Seizures,
      generalized in 71.2%, and focal in 28.8% were generally of low occurrence with
      good therapeutic response. Background EEG activity was normal in most patients.
      During follow-up, the clinical and EEG features remained unchanged. In a control
      series of 92 nonepileptic subjects with diffuse CA, CCA was noted in only 4
      (4.3%). No variation in grade or distribution of CCA was noted in repeated CT
      scans of the two groups, except in 2 epileptic patients. Psychometric tests
      demonstrated no cognitive impairment during evolution. The results appear to
      confirm the hypothesis that late-onset epilepsy associated with CCA constitutes a
      syndrome that is related to the characteristics of the atrophy.

PMID- 1396424
TI  - Gyratory epilepsy in a patient with a thalamic neoplasm.
AB  - A patient with a right thalamic oligodendroglioma developed seizures
      characterized by circling behavior, speech arrest, and secondarily generalized
      seizures. Gyratory epilepsy is relatively uncommon and may either represent a
      benign form of primary generalized epilepsy or occur secondary to a focal
      cortical lesion. Thalamic stimulation has been shown experimentally to induce
      circling movements, but no other clinical cases with a thalamic lesion have been
      described.

PMID- 1396425
TI  - Nonconvulsive status epilepticus in adults: thirty-two consecutive patients from
      a general hospital population.
AB  - We studied all adult patients who between 1984 and 1989 were initially diagnosed
      at our hospital as having nonconvulsive status epilepticus. Thirty-two patients
      fulfilled the criteria, which included ictal EEG recordings. The annual incidence
      was 1.5 in 100,000 inhabitants. The median age at onset of status was 51 years.
      Ten patients had status as their first epileptic manifestation, but most patients
      had a previous history of epilepsy. Median duration of epilepsy at onset of
      status was 4 years. Fourteen patients had focal ictal seizure activity on EEG and
      thus met the criteria for complex partial status. Eighteen patients had
      generalized seizure activity on EEG, but only 6 of these had a history of absence
      epilepsy or juvenile myoclonic epilepsy. None had Lennox-Gastaut syndrome. The
      clinical features of status in the remaining 12 patients were in some respects
      similar to those of the patients with complex partial status. We hypothesize that
      the EEG seizure activity in these patients may have been generalized from an
      initial focus.

PMID- 1396426
TI  - Visuomotor coordination during focal and generalized EEG discharges.
AB  - A new computer-based method for continuous gauging of momentary, visuomotor
      coordination under simultaneous EEG control proved both effective and suitable
      for children. Thirty-eight patients (age 4-17 years) who had different types of
      hypersynchronous activity were examined: None of the patients with focal
      discharges showed significant impairment in the test performance. Slight losses
      were evident in less than 3-s generalized, irregular spike-wave paroxysms.
      Deterioration was particularly evident in the bilateral synchronous 3-Hz spike
      wave series, which lasted greater than 3 s.

PMID- 1396427
TI  - Placebo-controlled pilot study of centromedian thalamic stimulation in treatment
      of intractable seizures.
AB  - Stimulation of centromedian (CM) thalamic nuclei has been proposed as a treatment
      for seizures. We implanted programmable subcutaneous (s.c.) stimulators into CM
      bilaterally in 7 patients with intractable epilepsy to test feasibility and
      safety. Stimulation was on or off in 3-month blocks, with a 3-month washout
      period in a double-blind, cross-over protocol. Stimuli were delivered as 90
      microseconds pulses at 65 pulses/s, 1 min of each 5 min for 2 h/day, with voltage
      set to half the sensory threshold. Stimulation was safe and well-tolerated, with
      a mean reduction of tonic-clonic seizure frequency of 30% with respect to
      baseline when stimulator was on versus a decrease of 8% when the stimulator was
      off. There was no improvement in total number of generalized seizures with
      stimulation, and treatment differences were not statistically significant.
      Stimulation at low intensity did not alter the EEG acutely, but high-intensity
      stimulation induced slow waves or 2-3 Hz spike-waves with ipsilateral frontal
      maximum. In an open-label follow-up segment with stimulator trains continuing for
      24 h/day, 3 of 6 patients reported at least a 50% decrease in seizure frequency.
      There were no side effects. This pilot project demonstrated the feasibility of
      controlled study of thalamic stimulation in epilepsy, but further study will be
      needed to demonstrate efficacy.

PMID- 1396429
TI  - Anatomic correlates of interhippocampal seizure propagation time.
AB  - The relation between interhippocampal seizure propagation time (IHSPT) and
      anatomic alterations in the human epileptic hippocampus may provide insight into
      the pathophysiology of temporal lobe epilepsy (TLE). Using depth electrode
      recordings, we measured the time required for spontaneous seizures with onset in
      one hippocampus to become manifest in the contralateral hippocampus in 50
      patients who underwent resection of the temporal lobe of seizure origin. Cell
      densities in individual hippocampal subfields were determined and correlated with
      mean IHSPT for each patient. Mean IHSPT was significantly and inversely
      correlated with cell counts in CA4 only (r = -0.38, p less than 0.01, Pearson's
      product correlation; r = -0.52, p less than 0.001, Spearman's rank order
      correlation). In 5 patients with bilateral independent hippocampal seizure onset
      who had temporal lobectomy and a diagnosis of mesial temporal sclerosis, mean
      IHSPT was consistently longer from the sclerotic temporal lobe than to it. These
      observations suggest that anatomic changes associated with chronic epilepsy alter
      propagation patterns. Because CA4 is believed to modulate the output of dentate
      granule cells and also has commissural connections to the contralateral homotopic
      area, the association of decreased CA4 cells with prolongation of IHSPT suggests
      that the observed anatomic alterations may actively (through increased
      inhibition) or passively (through decreased recruitment) interfere with various
      routes of seizure propagation.

PMID- 1396428
TI  - Temporal neocorticectomy in management of intractable epilepsy: long-term outcome
      and predictive factors.
AB  - We report the results of a long-term follow-up study of 50 patients who underwent
      removal of temporal neocortex with preservation of deeper limbic structures as
      surgical therapy for intractable temporal lobe epilepsy. The follow-up period
      ranged from 3 to 15 years. Preoperative EEG investigations were based on
      interictal discharges alone. Three factors were predictive of a good outcome: (a)
      A clear unilateral anterior-midtemporal focus (p less than 0.01), (b)
      stereotypical onset of temporal lobe seizure (p less than 0.005), and (c) greater
      volume of tissue removed at operation (p less than 0.05). Overall results showed
      that 62% of patients experienced an outcome of "cure" or "almost cure," as
      classified according to a modified version of Crandall's criteria (Crandall's I
      and II). Those who experienced a significant reduction in seizures but who
      continued to have intractable epilepsy (Crandall's III) were not considered to
      have had a good result. Overall outcome compares favorably with other that of
      centers using different surgical approaches and indicates that neocorticectomy is
      a suitable procedure in a highly selected population even when limited resources
      are available.

PMID- 1396430
TI  - Ictal and interictal activity in partial epilepsy recorded with multichannel
      magnetoelectroencephalography: correlation of
      electroencephalography/electrocorticography, magnetic resonance imaging, single
      photon emission computed tomography, and positron emission tomography findings.
AB  - Ictal and interictal epileptic activity was recorded for the first time by
      multichannel magnetoencephalography (MEG) in three patients with partial
      epilepsy. Pre- and intra-operative localization of the epileptogenic region was
      compared. The interictal epileptic activity was localized at the same region of
      the temporal or frontal lobe as the ictal activity. Main zones of ictal activity
      were shown to evolve from the tissue at the centers of interictal activity. Pre-
      and intra-operative electrocorticography (ECoG) as well as postoperative outcome
      confirmed localization in the temporal and frontal lobe. Results also correlated
      with findings from scalp EEG, interictal and ictal single photon emission
      computed tomography (SPECT), positron emission tomography (PET), and magnetic
      resonance imaging (MRI). Combined multichannel MEG/EEG recording permitted dipole
      localization of interictal and ictal activity.

PMID- 1396431
TI  - Magnetic resonance imaging in localization of EEG depth electrodes for seizure
      monitoring.
AB  - Preoperative evaluation of patients with medically refractory complex partial
      seizures requires intensive EEG monitoring. Part of this process may include
      insertion of depth electrodes into temporal lobe structures. Although many
      imaging methods have been used for stereotactic placement of the electrodes, only
      computed tomography (CT) has been used to verify position after implantation. We
      studied 30 patients in whom magnetic resonance imaging (MRI) was used to
      visualize the position of stainless-steel electrodes stereotactically implanted
      in the temporal lobes. The procedure is noninvasive, does not utilize radiation,
      and has the additional advantages of multiplanar capability, increased soft
      tissue contrast, and lack of bony artifacts commonly associated with CT.

PMID- 1396432
TI  - Seizures during cognitive testing in patients with temporal lobe epilepsy:
      possibility of seizure induction by cognitive activation.
AB  - In 18 of 185 patients under consideration for epilepsy surgery, 20 seizures were
      observed during neuropsychological evaluation. We wished to determine whether the
      task at seizure onset corresponded neuropsychologically to lateralization of the
      epileptic focus. The patients' characteristics and the circumstances of the
      seizures were as follows: Fourteen patients had right temporal lobe epilepsy
      (RTE) and four had left temporal lobe epilepsy (LTE). Although a wide range of
      cognitive functions had been tested, all but one seizure occurred during
      assessment of memory performance. In the RTE patients, 12 of 16 seizures occurred
      during visual memory testing. Two seizures were observed during a verbal memory
      task, and one seizure was observed during mental rotation. In two LTE patients,
      seizures were elicited during verbal memory testing. Two LTE patients with
      seizures during visual memory testing had speech dominance of the right
      hemisphere. This high correspondence between the eliciting performance and the
      focus localization suggests that cognitive performances ipsilateral to the
      epileptic focus may affect seizure threshold in focal epilepsies.

PMID- 1396433
TI  - Psychosocial difficulties and outcome after temporal lobectomy.
AB  - One hundred fifteen consecutive patients in the Austin Hospital Comprehensive
      Epilepsy Program (Melbourne, Australia) were surveyed to document the
      psychosocial and rehabilitation difficulties after temporal lobectomy. During the
      follow-up period (mean 4 years) 3 patients died, 5 patients were lost to follow
      up, and 107 patients with family and friends were interviewed. Eighty-four
      patients (78%) had been seizure-free for the year preceding the interview; 13
      others had seizure reduction greater than 75%. Success in ablation or reduction
      in seizures correlated with the amount of postoperative gain, but in this series,
      analysis of work and dependency outcome did not emphasize areas of success.
      Although improvement in work and financial status, interpersonal relations and
      sexuality were all recorded, successful patients deemed that most advance had
      been made in the areas of newly acquired independence, enhanced career potential,
      and social freedom. Significant postoperative anxiety, especially after left
      temporal lobectomy, was noted, possibly explained by benzodiazepine antiepileptic
      drug (AED) discontinuation. Although 1 patient committed suicide, neither
      depression nor psychosis was common in the rehabilitation period, in contrast to
      results in previous series. Significant sociodomestic problems emerged from this
      survey, however: 35% of patients considered successes reported postoperative
      problems stemming from the necessity to restructure family dynamics; in 6%, this
      resulted in divorce. Moreover, 20% of patients and relatives reported significant
      behavioral problems in coping with the seizure-free lifestyle. Finally, the
      problems of the worsened situation after surgical failure indicated the
      counterproductive potential of ineffective lobectomy. These results indicate the
      necessity for a preoperative counseling program to prevent these problems.

PMID- 1396434
TI  - Antiepileptic drug treatment after temporal lobe epilepsy surgery: a randomized
      study comparing carbamazepine and polytherapy.
AB  - Temporal lobectomy is an effective treatment in selected patients with medically
      intractable temporal lobe epilepsy (TLE). Postoperative antiepileptic drug (AED)
      treatment guidelines have not been established, and patients are often treated
      with polytherapy postoperatively. We prospectively randomized 40 patients
      undergoing temporal lobectomy to monotherapy with carbamazepine (CBZ, 20) or to
      continuation of their presurgical polytherapy (20) to assess the efficacy and
      safety of each regimen during the first year after operation. No significant
      differences between groups were noted with respect to seizure recurrence rate and
      type or time of recurrence. Patients in the polytherapy group had a 30% incidence
      of drug-related side effects as compared with only 10% in the CBZ group. These
      results suggest that after temporal lobectomy for intractable epilepsy, patients
      can be safely treated with CBZ monotherapy and that treatment with multiple AEDs
      is not necessary.

PMID- 1396435
TI  - Lidocaine in refractory status epilepticus: confirmation of efficacy with
      continuous EEG monitoring.
AB  - Lidocaine was efficacious in 2 patients with refractory status epilepticus (RSE)
      unresponsive to several antiepileptic drugs (AEDs), including high-dose
      barbiturates. We confirmed the efficacy of lidocaine with, for the first time in
      adults, continuous EEG monitoring. Lidocaine, when properly used, may be a
      treatment option in RSE.

PMID- 1396436
TI  - Gamma-vinyl GABA (vigabatrin) in epilepsy: clinical, neurochemical, and
      neurophysiologic monitoring in epileptic patients.
AB  - We report long-term clinical, neurochemical, and electrophysiologic data of gamma
      vinyl GABA (GVG, vigabatrin) in three groups of patients. GVG was started as add
      on therapy for 75 patients with refractory complex partial seizures (group A) and
      for 36 mentally handicapped patients with severe epilepsy (group B). The third
      group (C) consisted of 20 patients with carbamazepine (CBZ) monotherapy, in half
      of whom GVG monotherapy was substituted. After 3 months, 55% of patients in group
      A and 42% in group B were responders (reduction in seizure frequency greater than
      50%). After 6 (group A) and 3 years (group B) of follow-up, 27 and 33% of the
      patients, respectively, still had good response to GVG. Neurochemical
      measurements showed a twofold increase in CSF GABA concentrations and minimal or
      no changes in other neurotransmitter-related parameters. In group C, substitution
      of GVG as medication tended to normalize the lengthened latencies in
      somatosensory evoked potentials (SEPs) observed during CBZ treatment.

PMID- 1396437
TI  - Gamma-vinyl GABA (vigabatrin): relationship between dosage, plasma
      concentrations, platelet GABA-transaminase inhibition, and seizure reduction in
      epileptic children.
AB  - The relationship between vigabatrin gamma-vinyl GABA (GVG, vigabatrin) daily
      dosage or steady-state plasma concentrations (CSS), platelet GABA-transaminase
      (GABA-T) inhibition, and seizure reduction were studied in 16 children with
      refractory epilepsy. After 2 months of observation and 1 month of single-blind
      add-on placebo, a fixed GVG dosage was added for 2 months. The dosage was then
      adjusted in two 2-month periods each, based on the patient's clinical response.
      In the fixed-dose period, GVG dosages of 56.8 mg/kg/day and CSS of 8.1 mg/L
      reduced GABA-T activity from 13.9 to 5.1 pmol/min/mg protein (p less than 0.001)
      and that of seizures from 51.4 to 22.3 seizures per month (p less than 0.01).
      Seizure reduction was correlated with dosage (r = 0.83, p less than 0.001), but
      not with CSS or with platelet GABA-T inhibition. After the GVG dose-adjustment
      periods, in which dosages of 84.4 mg/kg/day and CSS of 10.6 mg/L were reached,
      only a slight reduction was observed in both GABA-T activity (from 5.1 to 4.9
      pmol/min/mg protein) and seizures (from 22.3 to 18.1 seizures per month). In GVG
      responsive patients (excluding placebo-sensitive and GVG-resistant patients), a
      greater reduction of seizures was achieved (from 17.0 to 7.1 seizures per month,
      p less than 0.05), which was not accompanied by greater inhibition of GABA-T. GVG
      treatment in children should be started with a dosage of 50 mg/kg/day, increased
      to 75 or even 100 mg/kg/day when a partial response is observed. If seizures do
      not improve or if they become worse, the patient should be considered resistant
      and GVG should be discontinued.

PMID- 1396438
TI  - Total cholesterol, high-density lipoprotein cholesterol, and triglycerides in
      children receiving antiepileptic drugs.
AB  - The influence of antiepileptic drug (AED) therapy on total cholesterol (TC), high
      density lipoprotein (HDL) cholesterol, and triglycerides was studied in 208
      epileptic children compared with 175 normal children. A significant increase in
      TC plasma levels was observed with carbamazepine (CBZ), phenobarbital (PB), and
      phenytoin (PHT). The patients receiving valproate (VPA) showed levels very
      similar to those of the control population. The results may be explainable by the
      different biotransformation pathway of these drugs. HDL cholesterol and
      triglycerides were not altered by any of the AEDs. We recommend monitoring TC
      level in patients receiving CBZ, PB, and PHT and prescription of diet treatment,
      at least during the time of AED treatment.

PMID- 1396439
TI  - Electrochemistry of anticonvulsants: electron transfer as a possible mode of
      action.
AB  - Reduction potentials were determined for various anticonvulsants, including
      progabide, SL 75.102, CGS 9896, pyridazines, zonisamide, 1,2,3-triazoles, and
      copper complexes. The values generally were in the range of about -0.1 to -0.6 V
      for the protonated drugs and the metal complexes. Reduction potentials provide
      information on the feasibility of electron transfer (ET) in vivo. If the value is
      relatively positive (greater than about -0.6 V), the agent can act catalytically
      as an electron acceptor from an appropriate cellular donor. A concomitant
      favorable influence on abnormal neuronal processes associated with epilepsy could
      occur. We describe ET as a possible mode of action of anticonvulsants as well as
      some antiepileptic agents with no electrochemical data based on this hypothetical
      ET approach.

PMID- 1396440
TI  - Blood-brain barrier penetration of felbamate.
AB  - The brain uptake index (BUI) method of Oldendorf was used to examine blood-brain
      barrier (BBB) drug transport in mice, rats, and rabbits; felbamate (FBM)
      extraction (E) in a single transcapillary passage was 5-20%, and drug uptake in
      rat brain was not concentration-dependent. Like diazepam, FBM was retained in
      mouse brain. To ensure that radioactivity measurements reflected the disposition
      of parent drug and not some metabolite, extracts of mouse brain were prepared for
      further analysis. No FBM metabolites were detected in brain 5 min after
      administration: In silica gel thin-layer chromatography (TLC), a single [14C]FBM
      peak was detected--Rf = 0.504 (70:30 acetone:hexane). Confirmatory high
      performance liquid chromatography (HPLC) separations [30% methanol, 1.3 ml/min,
      C18 column, ultraviolet (UV) detection 254 nm] indicated a single peak containing
      greater than 93% of the radioactivity in the FBM fraction (12-min retention
      time). In a single transit through the liver (a nonbarrier tissue with
      fenestrated capillaries), FBM E was 82%. The octanol:buffered saline partition
      coefficient of FBM was (log PFBM =) 0.54 +/- 0.01. Thus, lipid-mediated BBB
      penetration of FBM is similar to that of phenytoin (PHT) and phenobarbital (PB).
      Plasma proteins do not affect FBM entry to the brain: neither human serum, nor
      bovine or human serum albumin (BSA, HSA), nor human alpha 1 acid glycoprotein
      (orosomucoid) significantly modified BBB FBM extraction. Erythrocyte-borne FBM
      may also dissociate and gain access to the brain in a single transcapillary
      passage. Differences between newborn and adult rabbit BBB FBM extraction and
      between different anesthetic agents are attributable to cerebral blood flow (CBF)
      rates. The permeability-surface area products (PS = [CBF].[E]) for FBM in rats,
      rabbits, and mice were 0.09, 0.16 and 0.30 ml/min/g, respectively. Preliminary
      autoradiographic analyses of frozen brain sections suggest that [14C]FBM
      distributes relatively uniformly throughout the brain and that minor variations
      apparently are a function of differing CBF rates.

PMID- 1396441
TI  - Pharmacokinetics of felbamate in pediatric and adult beagle dogs.
AB  - The relative bioavailability and pharmacokinetics of felbamate (FBM) after a
      single oral dose and after 10 once-daily oral doses of 60 mg/kg were investigated
      in adult and pediatric dogs of both sexes. The pediatric and adult dogs were aged
      4-6 weeks and 1-2 years, respectively. Analysis of variance (ANOVA) was performed
      on the bioavailability parameters among all groups and between the first and last
      doses. No sex-related differences in bioavailability and pharmacokinetic
      parameters were observed. The bioavailability of FBM in pediatric dogs was
      significantly less as compared with that in adult dogs. Rapid overall elimination
      of the drug in pediatric dogs appears to be responsible for the lower
      bioavailability. The bioavailability of FBM after the last dose was also
      significantly lower than after the first dose for both age groups. No major
      differences in the rate constant of FBM absorption (ka) and volume of
      distribution at steady state (VSS) were observed between the two age groups. As
      with other clinically useful antiepileptic drugs (AEDs), higher doses of FBM may
      be required in pediatric populations to achieve optimum drug levels, assuming
      that age-related changes in FBM disposition will also be confirmed in humans.

PMID- 1396442
TI  - Decreased sialidase activity in alveolar macrophages of guinea pigs exposed to
      coal mine dust.
AB  - The origin of immune dysfunctions that are observed in pneumoconiotic miners
      still remains unknown. There is evidence that the carbohydrate moiety of membrane
      glycoconjugates is of primary importance in many functions of immunocompetent
      cells. The glycosylation, and especially the sialylation level of membrane
      components of various lymphocyte and macrophage subsets, vary depending on the
      state of cellular differentiation and activation. Sialidases, which may regulate
      the amount of sialic acids exposed on the cell membrane, can thus be considered
      as immunoregulatory enzymes. In this report, the sialidase activity has been
      measured in alveolar macrophages (AM) and in cell-free bronchoalveolar lavage
      fluid (BALF) from guinea pigs exposed for 4 months to coal mine dust at a
      concentration of 300 mg/m3. The samples were collected by bronchoalveolar lavage
      2 months after cessation of exposure. The sialidase activity in the cell-free
      fluid and in the purified alveolar macrophages showed a 10-fold decrease (p less
      than 0.001). Kinetic parameters of the enzyme such as Km and optimum pH did not
      change. This changed activity was specific for sialidase, as two other lysosomal
      glycosidases, beta-galactosidase and N-acetylglucosaminidase, showed unchanged
      activities. These results suggest the possibility that, by inducing a decreased
      sialidase activity, exposure to coal mine dust may lead to a modified expression
      of AM membrane-associated sialic acids giving rise to altered immune functions
      (i. e., phagocytosis, antigen processing, response to cytokines, etc.).

PMID- 1396443
TI  - Factors affecting the in vitro dissolution of cobalt oxide.
AB  - In a recent interspecies comparison of the lung clearance of cobalt oxide
      (57Co3O4), differences of up to 4-fold were found in the translocation rates of
      57Co to blood between seven different animal species, including man. This study
      investigated some factors that could influence the dissolution of this material
      in vitro. The effect of bicarbonate and citrate concentrations (over
      physiological ranges) and medium pH on in vitro dissolution of 57Co from 57Co3O4
      particles was measured in a simple noncellular system. pH levels of 4.5, 6.1, and
      7.2 were used to correspond to those in the alveolar macrophage lysosome, its
      cytoplasm, and the extracellular lung fluid. Measurements of the fractional
      dissolution rate were made weekly for 3 months. pH had the greatest effect on
      dissolution rates, with particles suspended in the lowest pH medium (4.5)
      dissolving at a significantly faster rate than at higher pH values. Increasing
      citrate concentrations resulted in slightly higher dissolution rates, but there
      was no effect of bicarbonate concentration. There was no evidence of synergism
      between the factors studied.

PMID- 1396444
TI  - Recovery of rat alveolar macrophages by bronchoalveolar lavage under normal and
      activated conditions.
AB  - When rat (female Wistar) lungs were lavaged (bronchoalveolar lavage, BAL) six
      times with physiological saline, approximately the same number of alveolar
      macrophages (AM) were found in the first and second BAL, whereas in the third
      fourth, fifth, and sixth BAL, the number of AM decreased exponentially.
      Morphometric counting of the number of AM in histological sections of lung tissue
      showed that only 14% of the AM population had been recovered by BAL. Although
      additives to the BAL fluid such as lidocaine and/or fetal calf serum increased
      the AM count in the first washing considerably, the total number of AM washed out
      remained unaltered. Addition of the phagocytosis stimulant zymosan increased the
      AM count in BAL by a factor of more than 2. On stimulation of the lungs with an
      inert dust (silicon carbide), the AM count in the BAL and the lung was only
      slightly increased 8 weeks after intratracheal instillation. In contrast, after
      exposure to fibrogenic and cytotoxic quartz, the AM count in BAL and lung was
      significantly increased, and the recovery of AM had also increased by a factor of
      approximately 2. The experiments show that it is the micromilieu of the alveoli
      and the condition of the AM (certain physiological activation states, such as
      phagocytic activity) that essentially determine the degree of recovery.

PMID- 1396445
TI  - Intraphagolysosomal pH in canine and rat alveolar macrophages: flow cytometric
      measurements.
AB  - Intracellular dissolution of inhaled inorganic particles is an important
      clearance mechanism of the lung and occurs in phagolysosomal vacuoles of
      phagocytes. Flow cytometric measurements of intraphagolysosomal pH in alveolar
      macrophages (AM) obtained from beagle dogs, Wistar rats, and from a baboon were
      made using fluorescein isothiocyanate-labeled amorphous silica particles (FSP).
      AM were obtained by bronchoalveolar lavage. FSP were phagocytized by AM in cell
      suspensions incubated in full media for 24 hr up to 6 days. Dual laser flow
      cytometry was performed and six-parameter list mode data were recorded from
      forward scatter, side scatter, and fluorescence intensities at 530 nm excited at
      457 nm and 488 nm as well as logarithmic fluorescence intensity at wavelengths
      630 nm excited at 488 nm. In this way it was possible to discriminate viable AM
      with phagocytized FSP from lysing AM with phagocytized FSP and from cells without
      FSP and from free FSP. Viable cells were distinguished from lysing cells by
      staining with propidium iodide immediately before the flow cytometric
      measurement. A calibration curve for the pH value was determined from FSP
      suspended in buffered media at pH values ranging from 3.5 to 7.5. First flow
      cytometrical results indicated that after an incubation time of 24 hr, the mean
      intraphagolysosomal pH of viable AM was 4.7 +/- 0.3 for dogs and 5.1 +/- 0.5 for
      rats. The intraphagolysosomal pH of the baboon AM was 4.5.

PMID- 1396446
TI  - Intracellular particle dissolution in alveolar macrophages.
AB  - Aerosol particles deposited in the lungs that are not readily soluble in the
      epithelial lining fluid will be phagocytized by alveolar macrophages (AM). Inside
      the phagolysosomal vacuole, the constituents of the plasma allow dissolution of a
      variety of compounds at a higher rate than dissolution in extracellular lung
      fluids. Chelator concentration and a pH value of about 5 were found to control
      intracellular particle dissolution (IPD). Hence, IPD is the initial step of
      translocation of dissolved material to blood, which is an important lung
      clearance mechanism for particles retained long term. IPD rates of uniform test
      particles determined in human, baboon, and canine AM cultures were similar to
      initial translocation rates determined in lung clearance studies of the same
      species after inhalation of the same test particles. IPD rate in cultured AM
      proved to be a sensitive functional parameter of AM, which was used to identify
      changes in the clearance mechanism of translocation during different exposure
      conditions.

PMID- 1396447
TI  - In vitro dissolution of uranium oxide by baboon alveolar macrophages.
AB  - In vitro cellular dissolution tests for insoluble forms of uranium oxide are
      technically difficult with conventional methodology using adherent alveolar
      macrophages. The limited number of cells per flask and the slow dissolution rate
      in a large volume of nutritive medium are obvious restricting factors.
      Macrophages in suspension cannot be substituted because they represent different
      and poorly reproducible functional subtypes with regard to activation and enzyme
      secretion. Preliminary results on the dissolution of uranium oxide using
      immobilized alveolar macrophages are promising because large numbers of highly
      functional macrophages can be cultured in a limited volume. Cells were obtained
      by bronchoalveolar lavages performed on baboons (Papio papio) and then
      immobilized after the phagocytosis of uranium octoxide (U3O8) particles in
      alginate beads linked with Ca2+. The dissolution rate expressed as percentage of
      initial uranium content in cells was 0.039 +/- 0.016%/day for particles with a
      count median geometric diameter of 3.84 microns(sigma g = 1.84). A 2-fold
      increase in the dissolution rate was observed when the same number of particles
      was immobilized without macrophages. These results, obtained in vitro, suggest
      that the U3O8 preparation investigated should be assigned to inhalation class Y
      as recommended by the International Commission on Radiological Protection. Future
      experiments are intended to clarify this preliminary work and to examine the
      dissolution characteristics of other particles such as uranium dioxide. It is
      recommended that the dissolution rate should be measured over an interval of 3
      weeks, which is compatible with the survival time of immobilized cells in culture
      and may reveal transformation states occurring with aging of the particles.

PMID- 1396448
TI  - In vitro dissolution of curium oxide using a phagolysosomal simulant solvent
      system.
AB  - Detailed study of actinide oxide behavior in alveolar macrophages (AM) in vitro
      is limited because of the short life span of these cells in culture. We created
      an in vitro dissolution system that could mimic the acidic phagolysosomal
      environment for the actinide and be maintained for an indefinite period so that
      dissolution of more insoluble materials could be measured. The dissolution system
      for this investigation, consisting of nine different solutions of HCl and the
      chelating agent diethylenetriamine pentaacetate (DTPA) in distilled water, is
      called the phagolysosomal simulant solvent (PSS). In this system, both the pH and
      the amount of DTPA were varied. We could observe the effect of altering pH within
      a range of 4.0-6.0 (similar to that of the phagolysosome) and the effect of the
      molar ratio of DTPA to curium at 1000:1, 100:1, or 10:1. We chose curium
      sequioxide (244Cm2O3) to validate the PSS for actinide dissolution versus that
      occurring in AM in vitro because it dissolves significantly in less than 1 week.
      The polydisperse 244Cm2O3) aerosol was generated, collected on filters,
      resuspended, and added to the PSS solutions and to cultured canine AM. By
      comparing dissolution in the two systems directly, we hoped to arrive at an
      optimum PSS for future dissolution studies. PSS and cell culture samples were
      taken daily for 7 days after exposure and tested for the solubilized curium. The
      amount of soluble material was determined by ultracentrifugation to separate the
      insoluble Cm2O3 from the soluble curium in the PSS solutions and filtration for
      the cell-containing material.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396449
TI  - In vitro chemical and cellular tests applied to uranium trioxide with different
      hydration states.
AB  - A simple and rapid in vitro chemical solubility test applicable to industrial
      uranium trioxide (UO3) was developed together with two in vitro cellular tests
      using rat alveolar macrophages maintained either in gas phase or in alginate
      beads at 37 degrees C. Industrial UO3 was characterized by particle size, X-ray,
      and IR spectra, and chemical transformation (e.g., aging and hydration of the
      dust) was also studied. Solvents used for the in vitro chemical solubility study
      included carbonates, citrates, phosphates, water, Eagle's basal medium, and
      Gamble's solution (simulated lung fluid), alone, with oxygen, or with superoxide
      ions. Results, expressed in terms of the half-time of dissolution, according to
      International Commission on Radiological Protection (ICRP) classification
      (D,W,Y), varied for different hydration states of UO3, showing a lower solubility
      of hydrated UO3 in solvents compared to basic UO3 or UO3 heated at 450 degrees C.
      Two in vitro cellular tests on cultured rat alveolar macrophages (cells
      maintained in gas phase and cells immobilized in alginate beads) were used on the
      same UO3 samples and generally showed a lower solution transfer rate in the
      presence of macrophages than in the culture medium alone. The results of in vitro
      chemical and cellular tests were compared, with four main conclusions: a good
      reproducibility of the three tests in Eagle's basal medium the effect of
      hydration state on solubility, the classification of UO3 in terms of ICRP
      solubility criteria, and the ability of macrophages to decrease uranium
      solubility in medium.

PMID- 1396450
TI  - Role of alveolar macrophages in precipitation of mineral elements inhaled as
      soluble aerosols.
AB  - The lysosomes of several varieties of cells such as the tubular proximal cell of
      the kidney and the alveolar macrophage have the ability to concentrate and
      precipitate several elements inhaled in water-soluble form, usually as phosphate.
      The mechanism involved is attributed to the high acid phosphatase activity of
      lysosomes and can be considered as an in vivo Gomori reaction. Among the elements
      studied, most of them are chemotoxic or radiotoxic (Cr; group IIIA: Al, Ga, In;
      rare earths: La, Ce, Tm; actinides: Th, U). In the lung macrophage, this
      mechanism of intralysosomal concentration and precipitation may prevent the
      diffusion of these toxic elements through the alveolar membrane.

PMID- 1396451
TI  - Phagolysosomal pH and dissolution of cobalt oxide particles by alveolar
      macrophages.
AB  - We studied phagolysosomal pH in rabbit alveolar macrophages (AM) incubated with 0
      15 microM chloroquine. There was a dose-related increase in pH with chloroquine
      concentration. Electron microscopy showed that chloroquine increased lysosomal
      size. In a second experiment we studied dissolution of radiolabeled cobalt oxide
      particles by rabbit AM, phagolysosomal pH, and lysosomal size. The cells were
      incubated for 2 days with 0, 2.5, and 10 microM chloroquine. Size and pH
      increased with chloroquine concentration. Dissolution of cobalt particles by the
      AM did not clearly change with pH. In a third experiment, dissolution of cobalt
      oxide particles in 0.1 M acetate buffer in saline with pH 4.0, 5.0, and 6.0 was
      studied. At the same pH, dissolution in acetate buffer was faster than in the AM,
      and the dissolution appeared to decrease faster with increasing pH than in the
      AM. A simple model for dissolution of a particle in a phagolysosome was proposed.
      This model predicts the types of differences in dissolution between AM and
      buffered saline.

PMID- 1396452
TI  - The effect of gamma-irradiation on the adherent capacity and iron metabolism of
      alveolar macrophages in mice and rats.
AB  - The effect of external gamma-irradiation on the survival of alveolar macrophages
      (AM) and on the extracellular release of 59Fe from AM-ingested [59Fe]iron
      hydroxide colloid was investigated in vitro using cells from C3H mice and Wistar
      rats. 59Fe release from mouse AM was enhanced by irradiation in a dose-dependent
      fashion, but irradiation up to 112 Gy did not affect the release from rat AM.
      Cell survival of AM, measured by direct counting of cell nuclei of adherent AM or
      vital staining with crystal violet, decreased dose dependently in mice and rats,
      but mouse AM were more radiosensitive than rat AM.

PMID- 1396453
TI  - Effect of 60Co gamma-irradiation on the nonspecific cytotoxicity of alveolar
      macrophages in vitro.
AB  - This paper reports on the effect of radiation on the nonspecific cytotoxicity of
      rat alveolar macrophages (AM). AM (effector cells) of bacille Calmette-Guerin
      activated Wistar rats were irradiated with 60Co gamma rays in vitro to give doses
      of 0, 100, 300, and 500 Gy. Three hours after irradiation, the AM were cultured
      with human lung adenocarcinoma AGZY83-a and HeLa target cells in 125I
      deoxyuridine-containing media for 6 hr and the cytotoxicity indexes determined.
      The results indicated that the cytotoxicity indexes of AM against human lung
      adenocarcinoma cells and HeLa cells were 94.3 +/- 0.3% and 81.3 +/- 1.9%,
      respectively. The cytotoxicity indexes using an effector/target cell ratio (E/T)
      of 10 seemed to be greater than with ratios of 20 and 30. The cytotoxicity
      indexes of AM (7 rats), irradiated to give doses of 0, 100, 300, and 500 Gy,
      against adenocarcinoma cells at an E/T ratio of 10 were 87.9 +/- 8.4%, 65.4 +/-
      14.1%, 47.5 +/- 17.5%, and 36.7 +/- 9.7%, respectively. The significance of the
      nonspecific cytotoxicity of AM in the immunological elimination of tumors and the
      inhibitory effect of radiation on AM cytotoxicity are discussed.

PMID- 1396455
TI  - Activity testing of alveolar macrophages and changes in surfactant phospholipids
      after irradiation in bronchoalveolar lavage: experimental and clinical data.
AB  - This study presents results of bronchoalveolar lavage (BAL) after irradiation to
      the lungs in mice as well as clinical data. The number of BAL cells, mainly
      macrophages, lymphocytes, and granulocytes, changed in a time-dependent manner.
      The phagocytic activity of the macrophages measured as the phagocytosis of
      microbeads and measured as the esterase activity also showed a strong time
      dependent increase during the acute phase up to 21 days after irradiation. The
      contents of surfactant phospholipids (SF) and sphingomyelin (SPH; as a parameter
      for cell death) were quantified by HPLC. Both were significantly changed between
      day 2 and 21 after irradiation. Three BALs of a patient with idiopathic
      interstitial pneumonitis, who had received an allogenic bone marrow graft after
      total body irradiation with 10 Gy, showed similar effects in the cellular and
      surfactant parameters. These data indicate that there are positive interactions
      between the number of different BAL cells, macrophage activity, and SF and SPH
      content in the preclinical model of the mouse as well as in the clinical
      situation after lung irradiation.

PMID- 1396457
TI  - Irreversible pulmonary changes induced in rat lung by dust overload.
AB  - The objective of this study was to investigate whether the effects of dust
      overload are reversible upon cessation of subchronic exposure to test toner.
      Female rats were exposed 6 hr/day, 5 days/week for 3 months to a test toner at 0,
      10, and 40 mg/m3. The retained quantity of test toner in the lungs at the end of
      exposure was 0.4 and 3.0 mg for the low and high exposure groups, respectively.
      Fifteen months later, the corresponding values were 0.12 and 2.65 mg in the
      lungs. Alveolar clearance of tracer aerosols as well as cytologic and enzymatic
      parameters in the bronchoalveolar fluid was investigated at the end of exposure
      and subsequently up to 15 months later. The alveolar clearance of 59Fe2O3, 51Cr
      polystyrene, and 85Sr-polystyrene tracer aerosols was slightly retarded at the
      low and substantially impaired at the high exposure level. At the low exposure
      level, there was some recovery in the clearance behavior up to 6 months after
      exposure. In contrast, at the high exposure level there was no indication of a
      reversal of the impaired clearance. For the beta-glucuronidase activity and the
      number of polymorphonuclear cells, the pattern of the effects was similar to the
      effects on the half-time tracer particle clearance. In conclusion, the dust
      overload at a lung burden of 3 mg test toner in rats was persistent for at least
      15 months after termination of exposure.

PMID- 1396456
TI  - Reaction of alveolar macrophages to inhaled metal aerosols.
AB  - For more than a decade we have exposed rabbits to different metals, usually in
      soluble form, and investigated the effects on the lungs. The metal concentrations
      have been around 1 mg/m3,i.e., not more than a factor of 10 above occupational
      threshold limit values. The exposure periods have been 1-8 months (6 hr/day, 5
      days/week). We have studied especially the morphology and function of alveolar
      macrophages (AM), the morphology of alveolar type I and type II epithelial cells,
      and analyzed lung phospholipids. Several metals produce specific, complex
      effects. For example, metallic and soluble nickel (NiCl2) increase both number
      and size of the type II cells, increase the production of surfactant, and affect
      morphology and function of AM. Cobalt (CoCl2) induces a different effect on type
      II cells from nickel, causing the formation of nodules in these cells. Trivalent
      chromium [Cr(NO3)3] does not affect either type II cells or the amount of
      surfactant significantly, but markedly affects AM. The administered metals affect
      AM both directly and indirectly. For example, nickel induces an increased
      production of surfactant, resulting in overfed AM with an increased metabolic
      activity. However, nickel also induces a direct decrease in the release of
      lysozyme activity by AM. Our results emphasize the complexity of the effects on
      the lungs of inhaled agents, which can act both directly and indirectly on AM.

PMID- 1396458
TI  - Role of the alveolar macrophage in lung injury: studies with ultrafine particles.
AB  - We conducted a series of experiments with ultrafine particles (approximately 20
      nm) and larger particles (less than 200 nm) of "nuisance" dusts to evaluate the
      involvement of alveolar macrophages (AM) in particle-induced lung injury and
      particle translocation in rats. After intratracheal instillation of both
      ultrafine particles and larger particles of TiO2, we found a highly increased
      interstitial access of the ultrafine particles combined with a large acute
      inflammatory reaction as determined by lung lavage parameters. An additional
      experiment revealed that intratracheal instillation of phagocytized ultrafine
      TiO2 particles (inside AM) prevented both the pulmonary inflammatory reaction and
      the interstitial access of the ultrafine particles. Another experiment showed
      that the influx of polymorphonuclear cells (PMN) into the alveolar space
      unexpectedly decreased with higher doses of ultrafine particles, whereas alveolar
      epithelial permeability (protein leakage) increased. The divergence between PMN
      influx into the alveolar space and changes in alveolar epithelial permeability
      implies that they are separate events. Pulmonary inflammatory parameters
      determined by lung lavage analysis correlated best with the surface area of the
      retained particles rather than with their mass, volume, or numbers. Because
      higher doses resulted in an increased interstitialized fraction of particles, we
      suggest that inflammatory events induced by particles in the interstitial space
      can modify the inflammation in the alveolar space detectable by lung lavage. Our
      results demonstrate the dual role of AM for modifying particle-induced lung
      injury, i.e., both preventing such injury and contributing to it. We conclude
      that the increased pulmonary toxicity of ultrafine particles is related to their
      larger surface area and to their increased interstitial access.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396459
TI  - Dosimetric implications of pulmonary macrophage clusters observed within lungs of
      rats that have inhaled enriched UO2 particles.
AB  - Twenty-four Fischer 344 rats were exposed to enriched uranium dioxide (UO2)
      aerosols to give a mean initial lung burden of 291 +/- 89 (SD) micrograms. Groups
      of rats were killed at 1, 7, 180, 360, 540, and 720 days post-inhalation (PI).
      Their lungs were fixed and inflated. Sections cut from all five lung lobes were
      used to prepare CR-39 neutron-induced 235U fission fragment autoradiographs. A
      single traverse across a CR-39 autoradiograph of a tissue section, from the left
      lung of all the rats, was made using a motorized microscopic stage. The traverse
      was divided into 10 fields. The track counts per field were used to test for
      homogeneity of track distribution and to assess if there was any tendency for
      tracks to be related to the peripheral region of the lung. Full raster scans
      across the entire tissue image were made on left lung autoradiographs from two
      animals killed at each time point to assess the homogeneity of fission fragment
      track distribution throughout the entire section. There was no evidence of any
      temporal change in the proportion of tracks associated with the lung periphery.
      At all time points PI, the track distribution was significantly nonhomogeneous,
      suggesting a nonuniform pattern of tissue irradiation from the 234U alpha
      particles. At time points from 180 to 720 days PI, large clusters of macrophages
      were observed in some of the sections taken from all five lung lobes. The total
      number of macrophage clusters increased with time PI. These macrophage clusters
      produced many 235U fission fragment tracks within the CR-39
      autoradiographs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396454
TI  - Pulmonary and thoracic macrophage subpopulations and clearance of particles from
      the lung.
AB  - Pulmonary macrophages consist of several subpopulations that can be defined by
      their anatomical locations as well as by other criteria. In addition to the well
      known alveolar macrophages that reside on the alveolar surface, pulmonary
      macrophages also occur in the conducting airways, in various pulmonary
      interstitial regions, and, in some mammalian species, in the lung's intravascular
      compartment. Other thoracic macrophages of relevance to pulmonary defense and
      some lung disease processes are the pleural macrophages resident in the pleural
      space and macrophages present in regional lymph nodes that receive lymphatic
      drainage from the lung. Of the above subpopulations of pulmonary and thoracic
      macrophages, the alveolar macrophages have received the most experimental
      attention in the context of the pulmonary clearance and retention of deposited
      particles. Accordingly, less information is currently available regarding the
      roles other pulmonary and thoracic populations of macrophages may play in the
      removal of particles from the lower respiratory tract and associated tissue
      compartments. This report provides an overview of the various subpopulations of
      pulmonary and thoracic macrophages, as defined by their anatomical locations. The
      known and postulated roles of macrophages in the pulmonary clearance and
      retention of particles are reviewed, with particular emphasis on macrophage
      associated processes involved in the pulmonary clearance of relatively insoluble
      particles.

PMID- 1396460
TI  - Effect of bronchopulmonary lavage on lung retention and clearance of particulate
      material in hamsters.
AB  - Hamsters were exposed to an aerosol of fused aluminosilicate particles (FAP)
      labeled with 57Co. Three groups of animals were given bronchopulmonary lavage,
      beginning at either 1 week, 1 month, or 6 months after exposure. Each treated
      group was lavaged eight times over a period of 25 days. Each lavage involved 10
      saline washes of the lungs. For each group, about 60-70% of the body content of
      57Co at the start of lavage treatment was removed; nearly half of this was
      recovered in the first two lavages. A positive correlation was demonstrated
      between the macrophage content and 57Co activity of the washings. The subsequent
      fractional clearance rate of 57Co from lavaged animals was not significantly
      different from that in a group of untreated control animals.

PMID- 1396461
TI  - Alveolar macrophages and lung lesions after combined exposure to nickel, cobalt,
      and trivalent chromium.
AB  - In earlier inhalation exposures of rabbits, nickel increased the production of
      surfactant by type II cells, with secondary effects on morphology and function of
      alveolar macrophages. Cobalt induced mainly a nodular growth pattern of the type
      II cells. Trivalent chromium seemed to impair the capacity of macrophages to
      catabolize surfactant but did not affect the type II cells. We exposed rabbits by
      inhalation to combinations of nickel (0.6 mg/m3 as NiCl2) and trivalent chromium
      [1.2 mg/m3 as Cr(NO3)3] (Ni-Cr), cobalt (0.5 mg/m3 as CoCl2) and nickel (0.5
      mg/m3) (Co-Ni), or cobalt (0.5 mg/m3) and chromium (1.2 mg/m3) (Co-Cr) for 4
      months, 5 days/week, 6 hr/day. Alveolar macrophages, alveolar type II cells, and
      lung content of phospholipids were determined. All combined exposures induced
      more pronounced lung lesions than exposures for each of the metals. Phospholipid
      concentrations were significantly higher. There were significantly higher
      percentages of macrophages filled with surfactant-like inclusions and a smooth
      surface. Accumulations of macrophages in alveoli were more widespread. Chromium
      potentiated the effects of nickel and cobalt on the type II cells, which led to
      secondary effects on the macrophages. Nickel potentiated the specific effects of
      cobalt, i.e., type II cell nodule formation. The result indicates that noxious
      effects could also be induced in man by combined exposure to nickel, cobalt, and
      trivalent chromium in concentrations similar to those occurring in some
      occupational settings.

PMID- 1396462
TI  - Epithelial and extracellular matrix injury in quartz-inflamed lung: role of the
      alveolar macrophage.
AB  - The bronchoalveolar leukocytes from quartz-inflamed lung were separated into
      macrophage-enriched and neutrophil-enriched populations on density gradients.
      Neutrophil-enriched populations showed the greatest activity in causing injury to
      epithelial cells and fibronectin in vitro. Inflammatory macrophage-enriched
      populations from quartz-exposed lung had the ability to cause fibronectin
      degradation but could not cause detachment injury to epithelial cells over and
      above that caused by control alveolar macrophages. Fibronectin damage in vivo
      could be an important factor in disordering the connective tissue scaffold of the
      lung, thereby favoring fibrosis. In vitro quartz stimulated more production of
      cytokines by alveolar macrophages than the inert particulate titanium dioxide.
      Cytokines could be important in upregulating adhesion molecules in the membranes
      of lung cells in vivo; this process could aid leukocyte/lung cell contact,
      allowing epithelial injury to be expressed, and could also be a factor leading to
      pathological change.

PMID- 1396463
TI  - Sequential respiratory, psychologic, and immunologic studies in relation to
      methyl isocyanate exposure over two years with model development.
AB  - Of 113 methyl isocyanate (MIC)-exposed subjects studied initially at Bhopal,
      India, 79, 56, 68, and 87 were followed with clinical, lung function,
      radiographic, and immunologic tests at 3, 6, 12, 18, and 24 months. Though our
      cohort consisted of subjects at all ages showing a varied severity of initial
      illness, fewer females and young subjects were seen. Initially all had eye
      problems, but dominant symptoms were exertional dyspnea, cough, chest pain,
      sputum, and muscle weakness. A large number showed persistent depression mixed
      with anxiety, with disturbances of personality parameters. The early radiographic
      changes were lung edema, overinflation, enlarged heart, pleural scars, and
      consolidation. The persistent changes seen were interstitial deposits. Lung
      functions showed mainly restrictive changes with small airway obstruction; there
      was impairment of oxygen exchange. Oxygen exchange improved at 3-6 months, and
      spirometry improved at 12 months, only to decline later. The expiratory flow
      rates pertaining to large and medium airway function improved, but those for
      small airways remained low. There were changes of alveolitis in bronchoalveolar
      lavage fluid on fiber optic bronchoscopy, and in 11 cases positive MIC-specific
      antibodies to IgM, IgG, and IgE were demonstrated. On follow up, only 48% of the
      subjects were clinically stable, while 50% showed fluctuations. Thirty-two
      percent of the subjects had lung function fluctuations. Detailed sequential
      behavior over 2-4 years was predicted for dyspnea, forced vital capacity, maximum
      expiratory flow rate (0.25-0.75), peak expiratory flow rate, VO2, and depression
      score. A model for clinical behavior explained a total variance of 52.4% by using
      the factors of cough, PCO2 and X-ray zones in addition to above five parameters.
      The behavior of the railway colony group (1640 patients) revealed a similar
      pattern of illness. When this observed pattern of changes was transferred to the
      affected Bhopal city sections (with an equitable age-sex distribution), our model
      results were again validated. Thus the picture of MIC-induced disease seems
      similar despite the differences for age-sex and initial severity of illness in
      our cohort and in the population of Bhopal city as predicted by our model.

PMID- 1396464
TI  - Nonrandom distribution of breakpoints in the karyotypes of workers occupationally
      exposed to benzene.
AB  - The distribution of the breakpoints in the karyotypes of workers occupationally
      exposed to benzene was tested. Fifty-six workers exposed to benzene were
      investigated cytogenetically. A significant increase in chromosome aberrations
      was observed. The distribution of the breakpoints in the karyotypes of examined
      workers was significantly nonrandom (p less than or equal to 0.001). The
      breakpoints accumulated mainly on chromosomes 2, 4, and 7.

PMID- 1396466
TI  - Agricultural chemical utilization and human health.
AB  - The public is justifiably concerned about the human health effects of
      agricultural chemicals. The many gaps in information about the mechanisms of
      toxic action, human exposures, and the nature and extent of human health effects
      are large. Very few older pesticides, in particular, have been tested for human
      health effects. Workers who produce, harvest, store, transport, process, and
      prepare food and fibers are exposed to many chemicals that are potentially
      hazardous and that are used in agriculture. The occupational health of these
      workers has not been adequately studied, and protective efforts have sometimes
      been minimal. Valid and accurate risk assessment is best based on sound
      information about how chemicals, in this case agricultural chemicals, are
      involved in toxic events--their mechanisms of action. These health effects
      include tumor promotion, chronic and acute neurotoxicity, immunotoxicity, and
      reproductive and developmental toxicity. Another key part of risk assessment is
      exposure assessment. Fundamental studies of the toxicology of target organisms
      and nontarget organisms exposed to agricultural chemicals are needed to discover
      and develop better solutions to the problems of agricultural pest control,
      including better formulations, optimal application rates and public education in
      safety and alternative agricultural practices. The large number of pesticides
      that have never been adequately tested for effects on human health is
      particularly worrisome in light of emerging information about delayed nervous
      system effects.

PMID- 1396467
TI  - Nuclear testing and public health.

PMID- 1396465
TI  - Cancer risks from arsenic in drinking water.
AB  - Ingestion of arsenic, both from water supplies and medicinal preparations, is
      known to cause skin cancer. The evidence assessed here indicates that arsenic can
      also cause liver, lung, kidney, and bladder cancer and that the population cancer
      risks due to arsenic in U.S. water supplies may be comparable to those from
      environmental tobacco smoke and radon in homes. Large population studies in an
      area of Taiwan with high arsenic levels in well water (170-800 micrograms/L) were
      used to establish dose-response relationships between cancer risks and the
      concentration of inorganic arsenic naturally present in water supplies. It was
      estimated that at the current EPA standard of 50 micrograms/L, the lifetime risk
      of dying from cancer of the liver, lung, kidney, or bladder from drinking 1 L/day
      of water could be as high as 13 per 1000 persons. It has been estimated that more
      than 350,000 people in the United States may be supplied with water containing
      more than 50 micrograms/L arsenic, and more than 2.5 million people may be
      supplied with water with levels above 25 micrograms/L. For average arsenic levels
      and water consumption patterns in the United States, the risk estimate was around
      1/1000. Although further research is needed to validate these findings, measures
      to reduce arsenic levels in water supplies should be considered.

PMID- 1396468
TI  - Mechanisms, measurement, and significance of lung macrophage function.
AB  - Macrophages exist throughout the body. They have critical roles in the peritoneal
      cavity, bone marrow, skin, spleen, liver, and elsewhere. Their migratory
      patterns, phagocytic behavior, immunologic roles, and secretory potential are
      pivotal to both defense mechanisms and to the pathogenesis of disease.
      Macrophages have been implicated recently in such diverse disease processes as
      arthritis, AIDS, and juvenile onset diabetes. It is important to recognize the
      existence of other lung macrophages besides alveolar macrophages. Macrophages
      exist in small and large airways above and below the mucus. They may release
      chemotactic factors and a variety of mediators. They ingest and degrade antigens
      and are microbicidal. Interstitial macrophages are in direct contact with the
      extracellular matrix as well as other cells in pulmonary connective tissue such
      as fibroblasts. Thus, release of mediators or enzymes by interstitial macrophages
      can have a profound effect. Pulmonary intravascular macrophages are resident
      cells within the pulmonary capillaries of some species. They avidly remove
      particles and pathogens from circulating blood and secrete inflammatory
      mediators. Finally, pleural macrophages are involved in the fate and consequences
      of inhaled particles, especially fibers. A key attribute of macrophages is
      motility. Movement is an essential step in phagocytosis. There can be no particle
      binding or ingestion unless macrophage-particle contact occurs. To what extent
      and by what mechanisms do alveolar macrophages move on the alveolar epithelium?
      We have used optical methods as well as magnetometry to describe macrophage
      motility. Lung macrophages express an array of contractile proteins that are
      responsible for spreading, migration, phagocytosis, and the controlled
      intracellular motions of phagosomes and lysosomes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1396469
TI  - Heterogeneity of alveolar macrophages in experimental silicosis.
AB  - The alveolar macrophage (AM) population has been shown to be heterogeneous in
      composition as well as in function. The aim of our study was to assess
      morphological and functional features of AM in an experimental model of quartz
      induced lung fibrosis by flow cytometric methods. Twelve cynomolgus monkeys were
      exposed 8 hr/day, 5 days/week for 26 months to either normal atmosphere (n = 5)
      or 5 mg/m3 DQ12 less than 5 microns quartz dust (n = 7). After 20 months of
      exposure, we studied AM phagocytosis by incubating bronchoalveolar lavage cells
      with fluorescent polystyrene microspheres (mean diameter 1.91 microns). Using a
      fluorescence-activated cell sorter analyzer, AM subpopulations were identified
      via their volume/side scatter properties. After selective electronic "gating" of
      the AM populations, both the percentage of phagocytic AM and the mean number of
      ingested microspheres per AM were determined. In addition, a phagocytic index
      (microspheres/AM x % phagocytic AM x 10(-2) and a hypothetical total phagocytic
      capacity of one lung (phagocytic index x total number of AM x 10(-6) were
      calculated. The total bronchoalveolar lavage cell counts rose (75.6 +/- 11.3 x
      10(6) versus 10.1 +/- 0.8 x 10(6)) significantly after quartz exposure. In
      contrast, the percentage of phagocytic AM was significantly (p less than 0.05)
      reduced (43.5 +/- 5.0% versus 74.2 +/- 1.4%). Flow cytometric measurements
      revealed the appearance of an AM subpopulation characterized by size/granularity
      features identical to blood monocytes. Only minimal numbers of these cells were
      found under normal conditions, but they constituted 50% of the entire AM
      population in the quartz group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396470
TI  - Alveolar macrophage kinetics after inhalation of 239PuO2 by CBA/Ca mice: changes
      in synthesis of DNA.
AB  - For workers in the nuclear industry, the primary route for the entry of
      radioactive materials into the body is by inhalation, and the rate of clearance
      of particles from the pulmonary region of the lung is an important factor in
      determining radiation dose. It is the function of alveolar macrophages (AM) to
      maintain the sterility of the lung and to remove insoluble particles from the
      respiratory surfaces and airways. The AM population is not static, and under
      normal conditions the loss of macrophages from the alveoli via the conducting
      airways is balanced by renewal. Studies of the effects of external irradiation on
      the kinetics of AM are numerous, but to date little is known about the effects of
      inhaled radioactive particles. In this investigation the effects of inhaled
      239PuO2 (plutonium dioxide) particles on the synthesis of DNA by AM were studied
      at times up to 77 days after exposure. We also measured the number of cells
      recovered by bronchoalveolar lavage and the incidence of AM with nuclear
      aberrations. The latter provides a sensitive indicator of the effects of
      radiation. One of the earliest effects observed after exposure to 239PuO2 is a
      reduction in the number of AM recovered by lavage. This reduction is associated
      with a 3-fold reduction in the proportion of AM undergoing DNA synthesis at early
      times after exposure. The overall mean pulse labeling index of AM recovered from
      sham-exposed mice is 1.68%, and no trend is observed with time.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396471
TI  - Secretory and accessory cell functions of the alveolar macrophage.
AB  - We have attempted to address the requirements necessary for alveolar macrophage
      accessory cell function. We have also examined the in vitro and in vivo factors
      that must be taken into account when interpreting results from experimental
      studies. Differences in phenotypic expression by rat alveolar pleural and
      peritoneal macrophages are noted, as well as the differing expression of major
      histocompatibility complex (MHC) class II molecules. Furthermore, alveolar
      macrophages, harvested from rat lung, do not express the interleukin (IL)-1
      cytokines, and lipopolysaccharide (LPS) treatment of quiescent cells (after 24-hr
      in vitro culture) induces low levels of expression of IL-1 alpha and IL-1 beta.
      Short-term inhalation of refractory ceramic fibers, however, results in markedly
      increased IL-1 beta expression after stimulation with LPS. We suggest that, in
      vivo, IL-1 beta may be involved in the initial recruitment and activation of
      inflammatory cells rather than in induction of immune responses. We also
      postulate, based on recent published evidence, that alveolar macrophages activate
      the dendritic cells within the respiratory epithelium. Thus alveolar macrophages
      would release cytokines critical for the activation of dendritic cells during the
      afferent limb of the immune response, and they would respond to products of
      sensitized T-cells such as interferon-gamma and IL-4 to interact with T-helper
      cells in an antigen-specific MHC-restricted manner during the efferent limb of
      the response.

PMID- 1396472
TI  - Persistent inflammation and impaired chemotaxis of alveolar macrophages on
      cessation of dust exposure.
AB  - Rats were exposed by inhalation to coal mine dust, titanium dioxide, or quartz.
      The magnitude of the consequent inflammatory response was assessed by counting
      numbers and types of leukocytes in the bronchoalveolar lavage fluid. The
      magnitude of the inflammatory response reflected the toxicity of the dusts, with
      quartz eliciting the greatest recruitment of inflammatory leukocytes, coal mine
      dust less than quartz, and titanium dioxide eliciting no inflammation. To assess
      the persistence of the inflammation, groups of rats were maintained in room air
      for 30 or 60 days after cessation of dust exposure and then numbers of leukocytes
      were assessed. Bronchoalveolar leukocytes in rats exposed to coal mine dust were
      reduced after exposure, but in the quartz-exposed rats the numbers increased with
      time after exposure. The chemotactic responses of bronchoalveolar leukocytes from
      rats inhaling coal mine dust and quartz were reduced and remained so after a 30
      day recovery period. Their reduced ability to chemotact did not fully prevent
      macrophages from leaving the bronchoalveolar region of dust-exposed rats.
      However, it is likely that the delayed removal of inflammatory leukocytes with
      the potential to injure the lung tissue may contribute to septal damage and so
      contribute to the pathogenesis of pneumoconiosis.

PMID- 1396473
TI  - Effects of ozone exposure on lipid metabolism in human alveolar macrophages.
AB  - Alveolar macrophages (AM) store arachidonic acid (AA), which is esterified in
      cellular phospholipids until liberated by phospholipase A2 or C after exposure to
      inflammatory stimuli. After release, there can be subsequent metabolism of AA
      into various potent, biologically active mediators including prostaglandins and
      platelet-activating factor (PAF). To examine the possibility that these mediators
      may account for some of the pathophysiologic alterations seen in the lung after
      ozone (O3) exposure, human AM were collected by bronchoalveolar lavage of normal
      subjects, plated into tissue culture dishes, and the adherent cells were
      incubated with [3H]AA or [3H]lysoPAF. Human AM exposed to 1.0 ppm O3 for 2 hr
      released 65 +/- 12% more tritium, derived from [3H]AA, than paired, air-exposed
      controls into media supernatants. In other studies using a similar O3 exposure
      protocol, there was also a significant increase in human AM prostaglandin E2
      production (2.0 +/- 0.5-fold increase above air-exposure values, p less than
      0.01, n = 17). In additional studies, using a similar O3 exposure protocol (1.0
      ppm for 1 hr), there was also a significant increase in human AM PAF content (1.7
      +/- 0.2-fold increase above air-exposure values, p less than 0.02, n = 5). These
      potent lipid mediators, originally derived from human AM, may play an important
      role in the mechanisms of O3 lung toxicity.

PMID- 1396474
TI  - A new simplified dietary history method for measuring intake of energy and
      macronutrients.
AB  - In this dietary history method, which preserves the characteristic features of
      the full dietary history, the principle of simplification is to group several
      food items into common codes. This enables us to complete both an interview and
      all nutrient calculations within 35-45 min. In this study we investigated whether
      the method could replace a 4-day food record for assessing individual intakes of
      energy and macronutrients. Dietary data were collected from 75 individuals (57
      males and 18 females). Protein intake was validated by comparison with 24 h
      urinary nitrogen excretion (33 subjects), and energy intake was compared to
      weight maintenance energy intake from a later controlled diet study (19
      subjects). When average intakes according to the two methods were compared,
      dietary history intakes were slightly higher than food record results (0-13%)
      except for alcohol. Comparison with urinary nitrogen excretion and energy intake
      data indicate that this is due to an overestimation by the dietary history
      method, rather than an underestimation by the food record. For individuals most
      of the correlations between the two methods were in the range 0.5-0.7, but
      alcohol correlation was down to 0.2. About 75% (53-93%) of the individuals at the
      extremes of the intake distribution were classified similarly by both methods.
      Although the ability of the dietary history to predict the individual food record
      results was unreliable the two methods agreed better when classifying individuals
      relative to certain cut-off points (sensitivity and specificity values of 0.7
      0.9, relative to the food records).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396475
TI  - Metabolic responses to starch in bread containing intact kernels versus milled
      flour.
AB  - In the present study, the potential of including intact kernels from different
      cereals was evaluated as a means of developing bread with 'lente'
      characteristics. Postprandial glucose and insulin responses to bread products
      were studied in healthy subjects. In parallel, the in-vitro enzymic starch
      availability was investigated. Also studied were the contents of in-vitro
      indigestible starch. Coarse bread (CB) products composed of 80% pre-boiled
      kernels from wheat, rye, oats or barley and 20% white wheat flour were baked. In
      the case of barley, two forms for pre-treatments was used, boiling and scalding.
      A bread with 80% wholemeal barley flour and 20% white wheat flour (WMB) was also
      included and a white wheat bread (WWB) was used as reference. The glycaemic and
      insulinaemic indexes (GI and II, respectively) were calculated from the 95 and
      120 min incremental blood glucose and insulin areas. The GIs were significantly
      lower with CB from wheat, rye and barley than with WWB. In contrast, the GIs with
      CB from oats and WMB from barley were similar to that with WWB. The GIs and IIs
      were generally closely correlated. However, the II with CB from oats was
      significantly lower than with WWB despite similar GI. The GIs, and in particular
      IIs, were closely correlated with the hydrolysis rate index (HI) obtained in
      vitro, and this procedure can be recommended as a tool for ranking of starchy
      food. It is concluded that the botanical structure is an important determinant of
      the enzymic availability and hence of the metabolic responses. The in-vitro
      indigestible starch content was highest in CB from barley (1.2% dry weight basis)
      and lowest in CB from oats (0.5%).

PMID- 1396476
TI  - Postprandial thermogenesis in obese children before and after weight reduction.
AB  - The thermic effect of a meal (TEM) was measured in a group of 10 prepubertal
      obese children before (OB) and after (OA) weight reduction, and in a group of 10
      age-matched control children (C) of normal body weight. Following a hypocaloric
      balanced diet for 6 +/- 1 months, the obese children lost 5.2 +/- 1.3 kg i.e. 11%
      of their initial body weight. The thermic response to the mixed liquid meal - fed
      at an energy level corresponding to 30% of the 24 h premeal resting metabolic
      rate - was found to be significantly lower in OB than in C children (61 +/- 25
      kJ.3h-1 vs 79 +/- 21 kJ.3h-1, P less than 0.05), despite their higher test meal
      energy. After slimming, the TEM of obese children increased towards the controls'
      values (73 +/- 30 kJ.3h-1). These results support the hypothesis of the existence
      of a moderate thermogenic defect in some obese children which represents a
      consequence rather than an aetiological factor of obesity.

PMID- 1396478
TI  - Clinical signs of iron deficiency.

PMID- 1396477
TI  - The variation in blood lipid levels described by various measures of overall and
      abdominal obesity in Danish men and women aged 35-65 years.
AB  - The purpose of the study was to describe the proportion of the variation in blood
      lipid levels [high-density lipoprotein cholesterol (HDLC), low-density
      lipoprotein cholesterol (LDLC), total cholesterol, very-low-density lipoprotein
      cholesterol (VLDLC) and triglycerides] explained by different measures of overall
      obesity [body fat (kg), percentage body fat, or body mass index (kg/m2)] and
      abdominal obesity [waist/hip ratio, waist/thigh ratio or waist circumference
      (cm)]. This was done in a Danish population sample of 1523 men and 1464 women
      aged 35-65 years. This was done to assess, on a population level, the effects on
      the different lipid levels to be expected from a possible reduction in the level
      of obesity. The proportion of the variation in lipid levels explained by the
      various measures of overall obesity differed only slightly, as did the proportion
      of the variation in lipid levels explained by the various measures of abdominal
      obesity. In men more of the variation in the blood lipids could be explained by
      overall obesity than by abdominal obesity, whereas in women the reverse was true.
      More of the variation in the lipids was explained by overall obesity in men than
      in women, but more of the variation was explained by abdominal obesity in women
      than in men. In women the obesity measures predicted between 0% and 11% of the
      variation in lipid level, and in men the obesity measures predicted between 0%
      and 14% of the variation. Between 16% and 30% in women and between 5% and 21% in
      men of the variation in the lipid levels could be explained by obesity, age and
      several lifestyle variables.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396479
TI  - Obesity: an inherited metabolic deficiency in the control of macronutrient
      balance?
AB  - It has generally been assumed that the body is 'energy blind' and calories from
      all three macronutrients contribute with the same value to energy balance. There
      is, however, accumulating evidence to suggest that during ad-libitum conditions
      energy balance is achieved by a separate regulation of carbohydrate, fat and
      protein balances. Regulation of carbohydrate balance has the highest priority in
      the hierarchy, which is appropriate because the limited glycogen stores are only
      capable of covering the carbohydrate oxidation for a few days. Due to the higher
      satiating power of carbohydrate and protein compared with fat, a reduction in the
      dietary fat/carbohydrate ratio produces a negative fat balance in normal subjects
      consuming the diet ad libitum, while an increase in dietary fat/carbohydrate
      ratio results in a positive fat balance and weight gain. Subjects with a
      genetically determined predisposition to obesity become obese when they are
      exposed to a particular range of environmental conditions. The available
      knowledge suggests that the genetic propensity to weight gain is caused by a
      susceptibility to dietary fat due to an impaired capacity to increase their
      lipid/carbohydrate oxidation when fed a high-fat/low-carbohydrate diet. This in
      turn promotes lipid storage, depletion of carbohydrate stores and increases
      appetite. By enlarging the fat stores, the accompanying insulin resistance and
      higher levels of circulating non-esterified fatty acids increase lipid oxidation
      until it is commensurate with the dietary fat intake. The development of obesity
      may therefore be viewed as a regulatory mechanism by which the impaired lipid
      oxidation rate is raised to match a high fat intake. However, by decreasing the
      dietary ratio of fat to carbohydrate, macronutrient balance may be achieved with
      a high energy expenditure and a normal body composition. The results support
      current dietary recommendations, but with less emphasis on carbohydrate source,
      and they are also applicable for the prevention and treatment of obesity.

PMID- 1396481
TI  - Influence of sterilization, drying and oat bran enrichment of pasta on glucose
      and insulin responses in healthy subjects and on the rate and extent of in vitro
      starch digestion.
AB  - The effects of sterilization and oat bran enrichment of pasta on the glucose and
      insulin responses in healthy subjects were evaluated. Cooked and canned spaghetti
      and cooked fettucini without and with enrichment with oat bran (28%) were
      compared. Further, the effects of various low- and high-temperature drying
      conditions for spaghetti, cooking time and sterilization on the starch digestion
      rate and content of enzyme-resistant starch (RS) in vitro were also studied.
      Various cooking quality data were also determined to allow interpretation of
      results. The incremental glucose area (0-120 min) produced by canned spaghetti
      was twice the area of that produced by cooked spaghetti (69.03 vs 35.45 mmol/l x
      min, P less than 0.01). The incremental insulin area (0-120 min) was also
      significantly higher with canned spaghetti (17,500 vs 12,600 pmol/l x min, P less
      than 0.05). The rapid digestion was caused by excessive swelling of starch during
      sterilization that promoted a very soft texture of the spaghetti. Enrichment of
      fettucini with oat bran reduced slightly the incremental insulin area (15,600 vs
      20,100 pmol/l x min, P less than 0.05, for 0-120 min), but did not significantly
      reduce the glucose area. Drying conditions and cooking times could be varied
      within broad limits without affecting the rate of starch digestion in vitro of
      cooked spaghetti. In sterilized spaghetti the content of resistant starch was
      higher than that found in cooked 'al dente' spaghetti (2.2-3.4 vs 0.5 mg/100 mg
      total starch). In conclusion, sterilization influences the nutritional properties
      of starch in pasta by substantially increasing the glucose and insulin responses
      and by formation of resistant starch. The effect of oatbran environment is
      restricted mainly to a slight decrease in the insulin response.

PMID- 1396480
TI  - Effects of an oat bran concentrate on serum lipids in free-living men with mild
      to moderate hypercholesterolaemia.
AB  - An oat bran concentrate was prepared by removing non-fibre components by cold
      water wet-milling, resulting in a 2- to 3-fold concentration of soluble fibre,
      with beta-D-glucan as its main component. The concentrate was baked in bread
      which was consumed for 8 weeks by free-living men with mild to moderate
      hypercholesterolaemia. The effects on serum lipids were assessed in a randomized,
      double-blind, placebo-controlled trial. Despite the large daily dose (11.2 g) of
      beta-glucan, the beta-glucan-enriched bread had only a small and statistically
      non-significant effect on serum lipid concentrations. Probable reasons for the
      weakness of the effect could be the poor solubility of beta-glucan in the
      preparation, its enzymatic hydrolysis after ingestion, and the consequently low
      viscosity in the intestine.

PMID- 1396482
TI  - An in vitro procedure based on chewing to predict metabolic response to starch in
      cereal and legume products.
AB  - A new method for measuring the rate of in-vitro starch digestion in products with
      a structure 'as eaten' is introduced. An equivalent amount of potentially
      available starch from each product was chewed by subjects, expectorated into a
      beaker and incubated with pepsin. The incubate was thereafter transferred to a
      dialysis tubing and incubated with pancreatic alpha-amylase for 3 h. Samples were
      removed from the dialysate at time intervals and the degree of hydrolysis was
      calculated as the proportion of the potentially available starch degraded to
      maltose. A hydrolysis index (HI) was calculated as the area under the hydrolysis
      curve with the product as a percentage of the corresponding area with white wheat
      bread. The method was applied to 21 cereal and legume products, chosen to cover
      as wide a range as possible with respect to metabolic response, and to include
      several of the proposed mechanisms to differences in metabolic behaviour of
      starch. The accuracy of the in-vitro method was evaluated versus the metabolic
      responses obtained with the same products in healthy subjects. A significant
      correlation between HI and glycaemic index (GI) was obtained in cereal as well as
      in legume products. A significant correlation was also obtained between HI and
      insulin index (II) with pooled data from all products. However, in the case of II
      no correlation was obtained with the legume products only. It is concluded that
      the presently described in-vitro procedure offers a good potential to predict the
      metabolic behaviour of starchy foods.

PMID- 1396483
TI  - The effects of a 2-year switch from a mixed to a lactovegetarian diet on trace
      element status in hypertensive subjects.
AB  - Trace element status of 20 hypertensive subjects (14 women and 6 men, mean age 52
      years) was compared to that of normotensives. The changes in trace element
      status, body weight and blood pressure after a 2-year switch from a mixed to a
      lactovegetarian diet were also compared between these groups. The concentration
      of copper in plasma and that of lead in hair were higher in hypertensive subjects
      than in normotensives, but the concentrations of zinc, magnesium and selenium in
      plasma, urine and hair were similar to those of normotensives. In the
      hypertensive subjects, 3 months after the diet shift there was a decrease in the
      concentrations of zinc in plasma, hair and urine, that of copper in plasma and
      hair, of magnesium in urine, of selenium in plasma and hair, and an increase in
      the magnesium content in plasma and hair. Also the concentrations of mercury,
      lead and cadmium in hair decreased after the diet switch. Among the
      hypertensives, the relative increase of magnesium in plasma was greater than that
      of normotensives; their relative decreases of selenium and lead in hair were
      lower, that of cadmium greater and that of copper in urine was lower. Four years
      after the start of the experiment when most subjects had resumed a mixed diet,
      mineral and trace element concentrations in plasma, hair and urine were similar
      to their baseline levels. Three months after the diet switch the relative
      decrease in body weight was more marked among hypertensive women (5%) than in
      female normotensives (3%), but similar among men of both groups (5%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396484
TI  - Iodide excretion before and after revision of goiter prophylaxis (Dutch Nutrition
      Surveillance System).
AB  - To assess the iodine supply in The Netherlands after the revision of the goiter
      prophylaxis measures (Bread Act of 1982, with an increase of iodine content of
      bread salt) the data of a nationwide survey among Dutch elderly people conducted
      in 1984/1985 were analysed. Iodide excretion in 24 h urine samples was used as
      the main iodine status indicator. The data were compared with data on iodine
      nutriture obtained among an elderly population in The Netherlands before the
      revision of goiter prophylaxis. High prevalences (greater than or equal to 37%)
      of low iodine excretion (less than 0.78 mumol/24 h; 100 micrograms/24 h) were
      found for Dutch elderly people. Mean urinary iodide excretion was 0.95 mumol/24 h
      (121 micrograms/24 h) for men and 0.79 mumol/24 h (100 micrograms/24 h) for women
      which is low, especially among women, in comparison with the United States
      recommended dietary allowance (118 mumol/day = 150 micrograms/day). Consistent
      positive associations of iodide excretion were found with urinary potassium and
      sodium excretion, bread consumption and total iodine intake. Bread, as the iodine
      carrier chosen for goiter prophylaxis in The Netherlands, was found to be the
      main dietary iodine source. No improvement in iodine nutrition was found among
      the elderly studied in 1984/1985 in comparison with an elderly population seen in
      1981. Therefore, it is concluded that the present measures regarding goiter
      prophylaxis in The Netherlands might be of limited effectiveness.

PMID- 1396486
TI  - A simple hypothesis for the development of obesity.

PMID- 1396485
TI  - Elevated plasma vitamers of vitamin B6 in patients with chronic renal failure on
      regular haemodialysis.
AB  - Plasma pyridoxal-5'-phosphate (PL-5'-P), pyridoxal (PL), pyridoxine (PN), and 4
      pyridoxic acid (4-PA) were measured by high-performance liquid chromatography
      (HPLC) in 39 patients (15 male, 24 female) with chronic fenal failure undergoing
      regular haemodialysis and 46 healthy controls (28 male, 18 female). All three
      vitamers of vitamin B6 and the metabolite were significantly elevated in the
      haemodialysis patients. Mean PL-5'-P and PN concentrations were 20 times the mean
      in controls. Only one patient took a vitamin B6 supplement. In view of the
      neurotoxicity of supranutritional intakes of PN in normal humans we suggest that
      supplements of PN be carefully monitored when administered to patients with
      chronic renal failure.

PMID- 1396487
TI  - I know distraction works even though it doesn't!
AB  - Resistance is high to findings negating commonsense beliefs. If McCaul, Monson,
      and Maki's (1992) four studies are taken seriously, we will address new questions
      about the components of analgesic interventions--specifically, whether
      distraction works only when combined with a competing affect, an analgesic
      cognition, or both. Addressing these questions should increase our understanding
      of the mechanisms involved in pain processing and may increase our ability to
      intervene and modify chronic as well as acute pain. Laboratory studies offer an
      efficient route to such understanding, although the question of generalization
      will always lurk in the background.

PMID- 1396488
TI  - Does distraction reduce pain-produced distress among college students?
AB  - College students in four experiments placed their hands in ice water (the cold
      pressor task) and reported their distress. They simultaneously engaged in
      different reaction-time (RT) tasks that varied in the amount of attention
      required for successful performance. In each experiment, which differed in
      numerous procedural details, RT, error-rate, and self-report measures all
      demonstrated that the distraction tasks differed in the degree of attention
      required. Greater distraction, however, failed to reduce physiological, self
      report, or behavioral responses to the cold-pressor task. These data call into
      question the hypothesis that attention mediates the process whereby distraction
      tasks reduce pain-produced distress.

PMID- 1396489
TI  - Stress, coping, and high-risk sexual behavior.
AB  - We examined the relation between stress, coping, and a high-risk sexual behavior
      (unprotected anal intercourse) in 398 nonmonogamous gay and bisexual men from the
      AIDS Behavioral Research Project in San Francisco. Unprotected anal intercourse
      during the previous month, the amount of stress experienced during the previous
      month in each of 10 domains, six types of coping (self-controlling coping, escape
      avoidance, distancing, planful problem-solving, seeking social support, and
      positive reappraisal), and spiritual beliefs and spiritual activities were
      assessed through self-report. There was no relation between stress and
      unprotected anal intercourse. However, there was a relation between coping and
      unprotected anal intercourse. Subjects who reported unprotected anal intercourse
      used sex more of the time to help cope with stressful situations than did
      subjects who did not report unprotected anal intercourse. Unprotected anal
      intercourse was negatively associated with seeking social support and spiritual
      activities and positively associated with self-controlling coping, which involves
      keeping one's feelings to oneself, and positive reappraisal. The findings suggest
      that social aspects of coping may be a key to understanding differences between
      those who engage in high-risk sexual behavior and those who do not.

PMID- 1396490
TI  - Stress, reactivity, and immune function in healthy men.
AB  - We examined the effects of acute psychological stress on lymphocyte proliferation
      and circulating levels of interleukin-1 and -2. Healthy men were exposed to two
      viewings of a gruesome surgery film and were asked to recall details of the film
      twice during a 30-min period. These subjects were compared to a nonstress control
      group. Lymphocyte proliferation to the mitogen concanavalin A (Con A; 5
      micrograms/ml) was decreased during and after exposure to the stressor when
      compared to the control group. This decrease was more pronounced in subjects
      exhibiting greater blood pressure reactivity while viewing the film than in
      subjects showing smaller blood pressure responses. None of the other
      immunological measures was significantly affected by the stressor. Cortisol was
      not correlated with lymphocyte responsiveness. Possible explanations for these
      results and implications for further research are discussed.

PMID- 1396491
TI  - Cognitive coping strategies and blood pressure responses to real-life stress in
      healthy young men.
AB  - Coping style is an important feature in the understanding of the relation between
      real-life stress and associated blood pressure (BP) responses. In this study, 10
      high- and 10 low-"self-focused-coping" (SFC) male college students were tested
      with ambulatory BP monitoring on two typical schooldays, one of which included an
      examination. It was found that the high-SFC subjects, defined as those who tend
      to keep to themselves and/or blame themselves in stressful situations, showed
      higher BP responses than the low-SFC subjects, but only on the exam day. Further,
      the high-SFC subjects showed higher BP during the exam but also had BP elevations
      that were sustained during other activities throughout the same day, including
      evening rest. These results are discussed in terms of the relation between
      psychological and physiological responding.

PMID- 1396492
TI  - Adult-child interaction during invasive medical procedures.
AB  - Adult-child interactions during stressful medical procedures were investigated in
      43 pediatric patients videotaped during a venipuncture procedure in the course of
      cancer treatment. Relations among six adult behavior categories (explain,
      distract, command to engage in coping behavior, give control to the child,
      praise, and criticize/threat/bargain) and three child behavior categories
      (momentary distress, cry/scream, and cope) were examined using correlational and
      sequential analysis. Results indicated that adult distraction resulted in
      increased child coping and reduced momentary distress and crying. Adult
      explanations, although a likely response to child distress and crying, did not
      result in a reduction of these behaviors. Attempts to give the child control
      reduced child crying. Implications for clinical interventions during painful
      medical procedures are discussed.

PMID- 1396493
TI  - Comparing the effectiveness of behavioral treatment for chemotherapy-induced
      nausea and vomiting when administered by oncologists, oncology nurses, and
      clinical psychologists.
AB  - Adequate control of side effects during medical treatment of cancer increases
      patient compliance and quality of life. Antiemetic drugs are not an effective
      treatment for the one in three cancer patients on chemotherapy who experience
      anticipatory nausea and vomiting (ANV); the behavioral treatment of systematic
      desensitization has been found effective for ANV when delivered by clinical
      psychologists. This study examined the effectiveness of systematic
      desensitization when delivered by medical personnel versus clinical
      psychologists. Seventy-two consecutive cancer patients with ANV were randomly
      assigned to no-treatment control or to systematic desensitization from 5
      behaviorally trained clinical psychologists, 6 clinical oncologists, or 10
      oncology nurses. The treatment was found effective in reducing anticipatory
      nausea, anticipatory vomiting, posttreatment nausea, and posttreatment vomiting
      compared to control patients, with no significant differences in effectiveness
      found between clinical psychologists and oncology staff. Although medical
      personnel should not engage patients in psychotherapy or other interventions that
      cannot be completed successfully, they can treat patients effectively with
      systematic desensitization and should be encouraged to learn and use this and
      other behavioral intervention techniques to benefit total patient care.

PMID- 1396494
TI  - Assessing motivational readiness and decision making for exercise.
AB  - Motivational and cognitive processes of behavior change with respect to the area
      of exercise adoption were investigated. A total of 778 men and women, recruited
      from four worksites, answered a 40-item questionnaire consisting of statements
      based on constructs from the trans-theoretical model of behavior change.
      Principal-components analysis identified two factors--one a 6-item component
      representing avoidance of exercise (Cons), the other a 10-item component
      representing positive perceptions of exercise (Pros). Analysis of variance showed
      that the Pros, Cons, and a Decisional Balance measure (Pros minus Cons) were
      significantly associated with stage of exercise adoption. Results are consistent
      with applications of the model to smoking cessation and other areas of behavior
      change. Distinctions between exercise adoption and behaviors such as smoking
      cessation, weight loss, and alcoholism are discussed.

PMID- 1396495
TI  - Trait humor and longevity: do comics have the last laugh?
AB  - Four sets of biographical data were analyzed in order to test the hypothesis that
      the ability to generate humor is associated with longevity. Although steps were
      taken to ensure that tests had high levels of statistical power, analyses
      provided very little support for the idea that individuals with a well-developed
      sense of humor live longer than serious writers and other entertainers. In
      addition, a subsidiary analysis revealed that those in the business of
      entertaining others died at an earlier age than those in other lines of endeavor.
      These findings suggest that researchers should turn their attention from trait
      humor to the effects of humorous material.

PMID- 1396496
TI  - Culture and health-related schemas: a review and proposal for interdisciplinary
      integration.
AB  - We present a comprehensive review of anthropological, sociological, and
      psychological theory and data on the structure, content, and function of health
      related schemas. Health psychology's need to integrate specific variables and
      principles from the other disciplines is highlighted. Suggestions for future
      research are offered, and the importance of cultural factors in health beliefs is
      emphasized.

PMID- 1396497
TI  - Understanding the relations between smoking and body weight and their importance
      to smoking cessation and relapse.

PMID- 1396498
TI  - National working conference on smoking and body weight. Task Force 2: Methods of
      assessment, strategies for research.

PMID- 1396499
TI  - National working conference on smoking and body weight. Task Force 3:
      Implications with respect to intervention and prevention.

PMID- 1396500
TI  - Cigarette smoking and body weight: a personal journey through a complex field.

PMID- 1396501
TI  - Smoking and body weight: reactions and perspectives.

PMID- 1396502
TI  - National working conference on smoking and body weight. Task Force 1: Mechanisms
      relevant to the relations between cigarette smoking and body weight.
AB  - Careful, comprehensive, and empirical observations provide the building blocks of
      the sciences, whereas theory and mechanisms provide the "cement" to hold the
      blocks together and serve as blueprints to direct future building. This article
      resulted from several days of discussion regarding theories that may underlie the
      relation between cigarette smoking and body weight and the relation between
      smoking cessation and body weight. The working group composed of social and
      biological scientists who addressed this assignment considered what is already
      known within the smoking and body weight literature and also considered relevant
      findings from studies of smoking or body weight regulation that have not directly
      addressed the interaction of these variables. As expected, we were successful at
      listing some of what is not known and what is worth knowing. We also tried to
      identify fruitful possibilities for research activity that might clarify
      mechanisms of action and eventually lead to theoretical development. Because we
      do not believe that the present state of our deliberations merits the label of
      theories, we decided, instead, to report the summary of these deliberations as
      potential mechanisms relevant to the relation between smoking and body weight.

PMID- 1396503
TI  - Long bone fractures: evolving solutions.

PMID- 1396504
TI  - Is it possible to accelerate the restoration of a deficient skeleton?

PMID- 1396505
TI  - Readiness for birth; another piece of the puzzle.

PMID- 1396506
TI  - A comparison of congenital heart disease in horses and man.

PMID- 1396507
TI  - Plasma lipids, lipoproteins and post-heparin lipases in ponies with
      hyperlipaemia.
AB  - The metabolic origins of equine hyperlipaemia were investigated by analysing the
      concentration and composition of plasma lipoproteins in 18 ponies with the
      condition. The mean concentrations of cholesterol, triglyceride and very low
      density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively,
      compared with a control group of 18 healthy ponies. These increases were due to
      the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies.
      The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the
      particles were enriched in triglyceride and free cholesterol and depleted of
      cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100
      content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was
      1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but
      had normal complements of apoC-II and apoC-III. The conventional VLDL (called
      VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL
      contained increased amounts of apoE, apoC-II and apoC-III. The activities of
      lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism
      of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in
      response to the increased concentrations of their substrates. The composition of
      VLDL1 suggested that the liver was maximising the secretion of triglyceride by
      producing larger number of VLDL particles that accommodated a greater mass of
      triglyceride by having apoB-48 rather than apoB-100 as their structural protein.
      Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies,
      suggesting that increased FFA flux might be the stimulus for hepatic triglyceride
      synthesis and VLDL secretion. We conclude that overproduction, rather than
      defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid
      lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and
      FFA flux, are candidates for the management of hyperlipaemia.

PMID- 1396508
TI  - Five cases of gastrocnemius tendinitis in the horse.
AB  - The normal gastrocnemius tendon may contain some muscular tissue proximally. This
      results in a patchy echogenicity ultrasonographically where it lies caudal or
      lateral to the superficial digital flexor tendon (SDFT). When it has assumed a
      position dorsal (cranial) to the SDFT the gastrocnemius tendon has a more uniform
      echogenicity and its margins are well defined. Five horses had lameness
      associated with lesions identified ultrasonographically in the gastrocnemius
      tendon in the latter region. Lameness ranged from mild to severe and was
      characterised by reduced hock flexion, lowered arc of foot flight, shortened
      length of the cranial phase of the stride and in some horses a reduced duration
      of weight bearing during the caudal phase of the stride. Lameness was variably
      accentuated by flexion of the proximal or distal limb joints of the lame limb.
      Perineural analgesia of the tibial and fibular nerves or the tibial nerve alone
      substantially improved the lameness. All horses remained lame 2-3 months after
      initial examination, with minimal change in the ultrasonographic appearance of
      the lesion(s).

PMID- 1396509
TI  - Retrospective study of 38 cases of femur fractures in horses less than one year
      of age.
AB  - Medical records of 38 horses less than 1 year of age and diagnosed as having a
      fracture of the femoral diaphysis, metaphysis or distal physis were evaluated.
      Twenty-six foals had fractures of the femoral diaphysis or metaphysis with the
      most common fracture configuration being comminuted. Twelve foals had distal
      physeal fractures with the most common fracture configuration being a Salter
      Harris type II. Twenty-one foals with fractures of the capital femoral physis,
      neck or greater trochanter during the same time period were excluded from this
      study. Surgical repair was attempted in 16 diaphyseal and 2 distal physeal
      fractures. Most of the diaphyseal fractures were repaired by placing plates on
      the lateral and cranial surfaces of the bone. Dynamic condylar screw plates or
      angle blade plates were used for increased bone purchase in 4 foals with short
      distal fragments. Five foals with distal physeal fractures were treated; 2 were
      surgically treated by placing an angle blade plate on the lateral cortex, and 3
      foals with minimally displaced distal physeal fractures were managed with stall
      confinement. Eight of the 16 surgically repaired diaphyseal fractures healed.
      Fracture location and configuration was not a determinant of outcome, but the
      mean age of foals with successfully repaired diaphyseal fractures was 2 months
      compared with 4 months for the unsuccessful cases, indicating that the age and
      size of the foal was important. Long-term follow up revealed that 6 of the 8
      successfully repaired diaphyseal fractures had no residual effects of the
      fracture observed during performance of the horse for its intended use. Only 1 of
      the 2 surgically repaired distal physeal fractures healed, but this horse was
      eventually killed because of unthriftiness related to a malabsorption syndrome.
      Some form of complication developed in 13 of the 18 surgically repaired
      fractures. Infection was the primary cause of failure. The greatest determinant
      associated with infection was the inability to control post-surgical seroma
      formation.

PMID- 1396510
TI  - Tearing of the medial palmar intercarpal ligament in the equine midcarpal joint.
AB  - Tearing of the medial palmar intercarpal ligament is described in 45 intercarpal
      (midcarpal) joints in 42 horses (37 racehorses, 5 non-racehorses). Of the 37
      racehorses, there were 20 Quarter Horses, 14 Thoroughbreds and 3 Standardbreds.
      The patients had been referred for arthroscopic surgery for removal of
      osteochondral chip fragments that had been diagnosed radiographically or
      diagnostic arthroscopy of a persistent carpal problem. The problem was unilateral
      in 39 horses and bilateral in 3. The presenting clinical signs were lameness
      and/or persistent synovial effusion. In one instance, the presenting complaint
      was haemarthrosis. Osteochondral chip fragments were present in the joint
      affected with tearing in 23 horses. In 6 horses in which osteochondral fragments
      were present in other joints, the degree of synovial effusion was greatest in the
      midcarpal joint with ligamentous tearing. In most of the 22 midcarpal joints
      where carpal chip fragmentation and ligamentous tearing were present
      concomitantly, the degree of clinical compromise was greater than normally seen
      with that degree of osteochondral fragmentation. A ligament was designated as
      torn when a defect was present in the ligament. This usually took the form of
      frayed fibres suspended in the irrigating solution, presenting a transverse type
      of defect in the dorsal aspect of the lateral portion of ligament. However,
      longitudinal tearing was present in 1 case and tearing was noted in the palmar
      aspect of the ligament in 2 other cases. The shredded fibres were trimmed in most
      cases and this allowed better definition of the amount of ligament considered to
      be torn. The degree of damage ranged from 10% to 100% of the width considered to
      be torn.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396511
TI  - Idiopathic muscular hypertrophy of the equine small intestine: 11 cases (1980
      1991).
AB  - The medical records of 11 horses with idiopathic muscular hypertrophy (MH) of the
      small intestine were reviewed to determine the clinical and pathological features
      of the disease. The median age of affected horses was 10.0 years (range 5-18
      years). No breed or sex predisposition was apparent. Ten horses (91%) had chronic
      (23 days to 2.4 years) signs of mild, intermittent colic, and 1 horse had signs
      of severe colic of only 3 days' duration. Partial anorexia and chronic weight
      loss of variable duration (1-6 months) were prominent historical findings in 5
      (45%) horses. Diagnostic tests, with the exception of exploratory caeliotomy,
      were ineffective for definitive diagnosis of intestinal MH as a cause of colic.
      In 2 horses, however, a thickened, rigid ileum was detected by palpation per
      rectum, and in 5 horses, multiple loops of distended small intestine were
      detected by palpation per rectum. Hypertrophy of both the circular and
      longitudinal layers of muscularis was determined as the cause of intestinal
      thickening in all horses. Muscular hypertrophy of the ileum was present in 9
      (82%) horses. Two horses (18%) had MH of a section of jejunum only, and 4 (36%)
      horses had MH of the ileum in combination with MH of other sections of small
      intestine. Two (18%) horses had MH of the entire small intestine. In 9 (82%)
      horses, intestinal MH resulted in narrowing of the luminal diameter at the site
      of MH. Small diverticula were present on the mesenteric border of the
      hypertrophied ileum of 5 (45%) horses. Five linear (up to 150-cm) diverticula
      were present in the hypertrophied jejunum of 1 (9%) horse. Haemomelasma ilei was
      present on the antimesenteric serosal surface of affected intestine of 8 (73%)
      horses. Full-thickness rupture of the ileum with subsequent diffuse, septic
      peritonitis occurred in 3 (27%) horses.

PMID- 1396512
TI  - Arachidonate metabolites in bronchoalveolar lavage fluid from horses with and
      without COPD.
AB  - Arachidonate metabolites were measured in bronchoalveolar lavage fluid (BALF)
      from horses with (N = 4) and without (N = 7) chronic obstructive pulmonary
      disease (COPD). Prostaglandin (PG) D2, leukotriene (LT) B4 and LTC4 were present
      in highest concentrations in BALF from clinically normal horses. Concentrations
      of PGE2 and PGF were significantly higher in BALF from horses with COPD than in
      BALF from normal horses, but no differences were detected in thromboxane B2, 6
      keto-PGF1 alpha, PGD2, LTB4 or LTC4.

PMID- 1396513
TI  - Healing of full-thickness cartilage compared with full-thickness cartilage and
      subchondral bone defects in the equine third carpal bone.
AB  - The effect of lesion depth on the quality of third carpal bone cartilage repair
      was examined. A 1-cm diameter articular defect penetrating the calcified
      cartilage in one limb and the subchondral bone plate in the opposite limb was
      created in the radial facet of the third carpal bones. Clinical and
      xeroradiographic examinations were performed every 4 weeks until 4 months (3
      horses) and 6 months (3 horses) after surgery. The synovial membrane, non
      opposing articular surfaces and articular defects were examined grossly,
      histologically and histochemically. Grossly, deeper defects contained thicker,
      whiter tissue, but both joints contained generalised degenerative changes.
      Defects extending through calcified cartilage were filled deeply by
      fibrocartilage and superficially by fibrous connective tissue. Defects extending
      through subchondral bone were consistently filled with hyaline-like cartilage in
      the depths of the lesion, fibrocartilage in the intermediate layer and fibrous
      connective tissue superficially. The results indicate that subchondral bone is
      the source of hyaline-like cartilage repair tissue and suggest that quality of
      healing of cartilage defects may be improved by penetrating the subchondral bone
      plate. It also appears that the synovitis associated with the procedure must be
      controlled before the procedure can be advocated for treatment of clinical cases.

PMID- 1396514
TI  - Comparison of two grafting methods in 4.0-mm drill defects in the third
      metacarpal bone of horses.
AB  - In 6 horses, bilateral metacarpal vertical series of three 4.0-mm unicortical
      drill holes were made. At random, one of each series of 3 holes was filled using
      a sternal 4.0-mm cancellous bone cylinder or a slurry of cancellous bone injected
      into the hole or left as an empty control. All horses had lateral metacarpal
      xeroradiographs at monthly intervals. Three horses (6 metacarpi) were examined
      post mortem after 4 months and 3 others after 6 months. Immediate through 4-month
      post-operative xeroradiographs demonstrated increased density in the holes with
      cancellous cylinders and no difference could be seen between the untreated
      controls and holes injected with slurry. From 5 months, no radiographic
      difference could be seen between the treatment groups. No consistent histological
      difference between treatment groups could be detected. In conclusion, no
      justification for clinical grafting of 4.0-mm unicortical dorsal metacarpal drill
      holes could be found.

PMID- 1396515
TI  - Intravenous catheterisation of foetus and mare in late pregnancy: management and
      respiratory, circulatory and metabolic effects.
AB  - The uterine and umbilical vessels of 12 pregnant ponies were catheterised to
      study foetal metabolism. The effects of this procedure on maternal and foetal
      cardiovascular, respiratory, metabolic and adrenocortical activity were monitored
      during and after surgery. Premedication with acepromazine-butorphanol-detomidine
      was followed by induction of anaesthesia with detomidine and ketamine and
      maintenance, using mechanical ventilation, with halothane in oxygen and nitrous
      oxide. Mean maternal arterial blood pressure was greater than 70 mmHg during
      anaesthesia and arterial oxygen tension remained over 100 mmHg. The foetuses were
      adequately oxygenated but were hypercapnic and lactic acidaemic. Most maternal
      and foetal blood gases and metabolites had returned to normal by 24 h, although
      foetal plasma lactate fell more slowly. The maternal adrenocortical discharge was
      less severe than reported previously and plasma cortisol had fallen to basal
      levels by 48 h after surgery. Foetal plasma cortisol remained low and did not
      change during or after surgery. Arterio-venous metabolite and gas tension
      differences across the uterine and umbilical circulations were slightly greater
      at operation than in the recovery period, suggesting that uteroplacental
      perfusion may have been impaired during surgery. Post-operative recovery of the
      mare and foetus was satisfactory and subsequent problems associated with the
      foetal catheters were not related to the anaesthesia or surgery.

PMID- 1396516
TI  - A lateral approach for synovial fluid aspiration and joint injection of the
      femoropatellar joint of the horse.

PMID- 1396517
TI  - Mixed venous blood gases in recumbent and upright positions in foals from birth
      to 14 days of age.

PMID- 1396518
TI  - Double outlet right ventricle and other associated congenital cardiac anomalies
      in an American miniature horse foal.

PMID- 1396519
TI  - Bacteraemia and pneumonia in a neonatal foal caused by Streptococcus pneumoniae
      type 3.

PMID- 1396521
TI  - Steady-state heat transfer and thermal zone spreading in gel isoelectric
      focusing.
AB  - The zone spreading caused by a transverse pH profile due to a temperature
      gradient through the thickness of a gel slab is estimated. The temperature
      difference (delta T) between the upper and lower gel surfaces can be calculated
      as a function of the electric power dissipated in the gel and the gel dimensions.
      It is found that when delta T is only 1 degree C the zone spreading due to this
      thermal excursion is as high as 0.5 mm. Thus, an admissible delta T is found to
      be equal to 0.2 degrees C, since this corresponds to a thermal zone spreading of
      only 0.1 mm, i.e. the same order of magnitude as the spatial resolution of a
      laser scanner. A thermal zone spreading of 0.1 mm is compatible with a resolving
      power of 0.01 pH unit, the current limit of conventional isoelectric focusing in
      amphoteric buffers. A requirement for the thickness of a gel slab is formulated:
      e.g., at 40 W applied power (over a gel surface area of 25 x 11 cm), a thermal
      zone spreading limited to 0.1 mm can only be obtained with a gel thickness of
      approximately 170 microns.

PMID- 1396520
TI  - Production of mitogen-contamination free alginates with variable ratios of
      mannuronic acid to guluronic acid by free flow electrophoresis.
AB  - Commercial alginates consisting of variable homopolymeric regions of beta-D
      mannuronic acid and alpha-L-guluronic acid, interspaced with regions of
      alternating blocks, are potent stimulators of macrophages and lymphocytes.
      Therefore, inflammatory reactions and fibrotic overgrowth of the beads result if
      Langerhans islets are encapsulated in raw alginate hydrogel beads (cross-linked
      with divalent cations). The result is random failure of the islets some time
      after transplantation. Analysis of raw alginates by using free flow
      electrophoresis demonstrated that commercial alginates contained at least 10-20
      fractions (characterized by different electrophoretic mobilities) which showed
      mitogenic activity. These fractions could be quantitatively separated from the
      alginic acids by free flow electrophoresis on a preparative scale. The purified
      alginates cross-linked with Ca2+ ions exhibited no mitogenic reactions as proved
      by an in vitro assay. In addition, examination of purified Ba2+ alginate beads
      implanted intraperitoneally in rats or mice for three weeks showed no fibrotic
      overgrowth in contrast to implants made from unpurified alginate.

PMID- 1396523
TI  - Concave Ferguson plots of DNA fragments and convex Ferguson plots of
      bacteriophages: evaluation of molecular and fiber properties, using desktop
      computers.
AB  - A desktop computer program evaluating physical properties of DNA and
      bacteriophages is presented. The analysis is based on data obtained from
      capillary and submarine-type agarose electrophoresis. Native molecular/particle
      properties and properties of the gel (or polymer) medium can be derived from
      electrophoresis at several gel concentrations. This is done conveniently by a
      computerized evaluation of the semi-logarithmic plot of mobility vs. gel
      concentration, designated the Ferguson plot. In application to most proteins,
      this plot is linear and computer programs exist to evaluate it. However,
      nonlinear Ferguson plots have assumed great importance in view of the fact that
      the plots are concave for DNA. Similarly, convex plots are important since they
      prevail in the electrophoresis of large particles in agarose. The computer
      program reported here is the first to (i) address concave Ferguson plots and (ii)
      allow for the evaluation of both cases using a desktop computer. Program ELPHOFIT
      version 2.0, a Macintosh application, is available upon request.

PMID- 1396522
TI  - Temperature gradient gel electrophoresis: rapid detection of alpha-1-antitrypsin
      deficiency carriers.
AB  - The homozygous state of the alpha-1-antitrypsin (alpha 1AT) deficiency variant Z
      is associated with severe liver damage in early childhood and progressive lung
      emphysema in adulthood. A single base transition (G to A in codon 342) in exon V
      is causing the severe disease. The Glu342 to Lys342 mutation can be detected
      conventionally by isoelectric focusing (IEF) or on the DNA level by the newly
      developed method of temperature gradient gel electrophoresis (TGGE). It is the
      aim of this study to describe the TGGE technique, to compare the results with
      conventional IEF, and to discuss its efficiency for different diagnostic
      applications.

PMID- 1396524
TI  - Increased electrophoretic mobility of sodium sulfite-treated jack bean urease.
AB  - Sodium sulfite is a widely used activity-protective agent for the storage of
      urease. However, this reagent produces a 10% increase in the anodic
      electrophoretic mobility of native urease. Changes in the hydrodynamic properties
      of the enzyme are not involved in that modification. The observed change is
      related to an increased negative charge of the protein molecule in the presence
      of sodium sulfite. The results are discussed in terms of sulfitolysis of the
      single disulfide bond in the urease monomer. It is remarkable that the
      modification occurs at neutral pH. Our results show that removing sodium sulfite
      and reversing its effect by treatment with 2-mercaptoethanol are required prior
      to any study involving native urease.

PMID- 1396525
TI  - Two-dimensional electrophoretic analysis of transformation-sensitive polypeptides
      during chemically, spontaneously, and oncogene-induced transformation of rat
      liver epithelial cells.
AB  - Recently, we described the establishment of a computerized database of rat liver
      epithelial (RLE) cellular polypeptides (Wirth et al., Electrophoresis, 1991, 12,
      931-954). This database has now been expanded to include the analysis of cellular
      polypeptide alterations during chemically (aflatoxin B1; AFB), spontaneously, and
      oncogene (v-Ha-ras, v-raf, and v-myc/v-raf)-induced transformation of RLE cells.
      Two-dimensional mapping of [35S]methionine-labeled whole cell lysate, cell-free
      in vitro translation products and [32P]orthophosphate-labeled polypeptides
      revealed subsets of polypeptides specific for each transformation modality. A
      search of the RLE protein database indicated the specific subcellular location
      for the majority of these transformation-sensitive proteins. Significant
      alterations in the expression of the extracellular matrix protein, fibronectin,
      as well as tropomyosin- and intermediate filament-related polypeptides (vimentin,
      beta-tubulin, the cytokeratins, and actin) were observed among the various
      transformant cell lines. Immunoprecipitation and Western immunoblot analysis of
      tropomyosin expression in four individual AFB-, as well as four spontaneously
      induced, and each of the oncogene-transformed cell lines indicated that five
      major tropomyosin (Tm 1-5) isoforms were variably expressed in the various cell
      lines, including one polypeptide tentatively identified as Tm6. Whereas
      alterations in tropomyosin expression appeared to be transformation-specific,
      alterations in the individual intermediate filament polypeptides were related
      more to the differentiation state of the individual cell lines rather than to the
      transformation phenotype. These studies extend our earlier efforts toward the
      establishment of a comprehensive computerized database of RLE cellular proteins
      and demonstrates how such a database may serve as a useful source for studies
      concerning the regulation of growth and differentiation as well as transformation
      of RLE cells.

PMID- 1396526
TI  - High resolution two-dimensional gel analysis of proteins in the central nervous
      system of larvae of Drosophila melanogaster.
AB  - An improved method of high resolution two-dimensional gel electrophoresis was
      used to study the patterns of protein synthesis in the central nervous system
      (CNS) of late instar larvae of Drosophila melanogaster. A small number of CNSs
      was radiolabeled with a mixture of 14C-labeled amino acids or with
      [35S]methionine, and the pattern of labeled proteins was analyzed. One thousand
      and forty-five polypeptides, 800 acidic (IEF) and 245 basic (NEPHGE), from the
      CNS of several wild-type strains have so far been separated and cataloged. All
      these polypeptides were numbered and compared with our catalog of polypeptides
      from wing imaginal discs, and quantitative or qualitative changes were detected
      in more than 23% of the polypeptides. When comparing patterns of label of CNSs we
      found small quantitative differences in the rate of synthesis between individuals
      of the same strain, not due to sexual differences, and a minute number of
      quantitative and qualitative differences between groups of individuals of
      different strains.

PMID- 1396528
TI  - DNA-protein interaction analysis using polyacrylamide gel electrophoresis and a
      simple and sensitive UV crosslinking procedure.
AB  - A simple and reproducible technique for DNA-protein interaction analysis is
      described using UV crosslinking and polyacrylamide gel electrophoresis, leading
      to visualization of the complexes as distinct and strong signals. It avoids
      incorporation of bromodeoxyuridine (BrdU) into DNA and requires no special
      equipment. It was successfully applied to an oligonucleotide sequence from within
      the first intron of the mouse myb proto-oncogene and nuclear extracts from a myb
      expressing cell line.

PMID- 1396527
TI  - Two-dimensional polyacrylamide gel electrophoresis reveals differences between
      osteoblast and fibroblast extracellular proteins.
AB  - Normal human skin fibroblast primary cell lines secrete over 50 proteins into
      culture medium. These have been mapped previously using two-dimensional
      polyacrylamide gel electrophoresis (2-D PAGE) and this technique has now been
      used to investigate extracellular protein secretion by human osteoblasts in
      vitro. We report the mapping of a number of consistent markers specific to the
      osteoblast. In particular, one protein chain with posttranslational modifications
      was found to be unique to the osteoblast extracellular protein map. The absence
      of the N- and O-glycoforms of collagenase from the osteoblast profile in this
      study concurs with findings reported using the immunoprecipitation functional
      assay and Northern blot analysis. The use of 2-D PAGE in phenotypic assessment
      provides a more complete analysis than the standard range of single-parameter
      tests for osteoblasts. Mapping of extracellular and cellular proteins in addition
      to bone matrix protein analysis will allow a comprehensive analysis of normal
      osteoblast function. This technique may also be applied to the study of
      osteoblasts in relation to bone disease and in assessing the phenotypic shift
      within a normal osteoblast culture.

PMID- 1396529
TI  - An experimental study of the effect of isoflurane on epileptiform bursts.
AB  - The effect of isoflurane on penicillin- and picrotoxin-induced epileptiform
      activity was tested using hippocampal slice preparations. Isoflurane reduced both
      the frequency of spontaneous epileptiform bursts and the number of population
      spikes within each burst in a dose-dependent manner. The last population spikes
      in the burst were most sensitive to the anesthetic, whereas the first 4-6 spikes
      were quite resistant and persisted until spontaneous activity was abolished at 3%
      isoflurane. Isoflurane increased the stimulus current required to evoke
      epileptiform bursts and shifted the relationship between stimulus current and
      population spike amplitude to the right. At 3% isoflurane, a dose that usually
      causes iso-electric EEG and abolishes all spontaneous epileptiform activity,
      responses could still be evoked, and then invariably had an epileptiform pattern.
      The maximum response was reduced compared to control and 1.5% isoflurane. With
      isoflurane there was a reduced tendency for activity to be transmitted from one
      region within the hippocampus to the other. This effect was also dose-dependent.
      However, transmitted activity always retained a typical epileptiform character,
      although the number of population spikes within a train to some extent decreased
      with increasing concentrations of isoflurane.

PMID- 1396530
TI  - Positive transfer of audiogenic kindling to electrical hippocampal kindling in
      rats.
AB  - Audiogenic seizures in genetically susceptible rodents are provoked by intense
      acoustic stimulations which result in a tonic seizure associated with a short
      flattening of the EEG. These seizures have been shown to involve primarily
      brainstem structures. Daily exposure to sound for 30-40 days produced a permanent
      change in the evoked seizure with development of facial myoclonias, rearing and
      falling, or of tonic-clonic seizures accompanied by high amplitude cortical spike
      and-wave discharges. Kindled audiogenic seizures appear similar to seizures
      kindled from amygdala or hippocampus, suggesting that repeated auditory
      stimulations cause a progressive propagation of the epileptic discharge toward
      limbic structures. To verify this hypothesis, the behavioral and EEG development
      of electrical hippocampal kindling has been studied in 7 non epileptic controls
      (NE), 8 acoustic susceptible (AS), and 8 audiogenic kindled rats (KAS). The
      behavioral and EEG development of the electrical hippocampal kindling was similar
      in the AS and the NE rats. However, 2 animals in the AS group but no controls
      exhibited behavioral running and bouncing during the course of hippocampal
      kindling. In the KAS group, the hippocampal kindling was clearly facilitated as
      compared to NE and AS: behavioral stage greater than or equal to 5 was reached in
      a mean of 4 stimulations in KAS versus 30 and 22 stimulations respectively in NE
      and AS groups. This positive transfer phenomenon suggests that during kindling of
      audiogenic seizures, epileptic discharge spreads from the brainstem to the
      forebrain and progressively involves the hippocampus.

PMID- 1396531
TI  - Effects of 3-hydroxy,3-ethyl,3-phenylpropionamide (HEPP) on rat models of
      generalized and focal epilepsy.
AB  - The GABA withdrawal syndrome (GWS) is a new model of focal epilepsy in which
      paroxysmal activity is induced through the interruption of a chronic,
      intracortical infusion of GABA. Preliminary studies have shown extraordinary
      resistance of this epileptogenic activity to classic anticonvulsants including
      diazepam, the most effective agent for treating status epilepticus. However, GWS
      can be inhibited by GABA itself. The rat with petit mal-like seizures is a
      genetic model of generalized non-convulsive epilepsy (GNCE), with behavioral
      characteristics and electrical (spike-and-wave discharges) signs resembling
      absences. Moreover, GABAmimetics aggravate this type of seizure. Rats with GWS
      induced by cessation of a localized GABA infusion (50 micrograms/microliters/h
      for 24 h), and the rat model of GNCE, were treated with HEPP, a new
      anticonvulsant agent. In the case of GWS, the drug produced a significant
      decrease of focal spike activity in animals which started discharging at low
      frequencies while in rats with higher frequency discharge, HEPP was without
      effect. HEPP administered on the second day of the GWS in naive rats had no
      effect. In rats with GNCE, doses of 50 and 100 mg/kg i.p. blocked the spike-and
      wave discharges. The higher dose produced sedation in this absence seizures
      model. Although the mechanism of action of HEPP is still unknown, its unique
      antiepileptic profile deserves further studies.

PMID- 1396532
TI  - Section of the corpus callosum in kainic acid induced seizures in rats:
      behavioral, electroencephalographic and neuropathological study.
AB  - Clinical and experimental data suggest that the role of corpus callosum in
      epilepsy includes synchronization, spread, excitation and inhibition. Section of
      the corpus callosum (SCC) is known to be a useful therapy in selected types of
      generalized epilepsy, i.e., tonic, atonic and generalized convulsive seizures,
      but not partial seizures which may be exacerbated by this procedure. The goal of
      this study was to determine the effect of SCC in the kainic acid (KA) model of
      limbic seizures in rats. Using several doses of KA (2.5, 5 and 10 mg/kg) injected
      systemically, we found a potentiation of the behavioral, electrographic and
      histological effects of KA in the SCC group of animals compared to the sham
      operated control rats. A low dose of kainic acid (2.5 and 5 mg/kg) induced status
      epilepticus in the SCC animals, but not in the sham-operated control rats. These
      data demonstrate that in the KA model of temporal lobe seizures, SCC not only
      fails to protect, but actually intensifies seizures. This finding is compatible
      with the hypothesis that there is an inhibitory influence, via the corpus
      callosum, of the non epileptic neocortex on its contralateral homologue in the
      kainic acid model.

PMID- 1396533
TI  - Corpus callosotomy in the lithium-pilocarpine model of seizures and status
      epilepticus.
AB  - Section of the corpus callosum (SCC) is a useful surgical therapy in selected
      types of epilepsy, i.e., tonic, atonic, and intractable generalized convulsive
      seizures. Experimentally, the effects of SCC have been documented in animal
      models of focal seizures as well as generalized seizures. The object of this
      study was to determine the effect of SCC on behavioral and EEG symptomatology in
      the lithium-pilocarpine model of seizures and status epilepticus in the rat. SCC
      was well tolerated. Fifty-seven percent of SCC animals never developed status
      epilepticus, while all control animals developed status epilepticus. None of the
      SCC animals died after 24 h but 59% of control animals died within 24 h of
      status. Histology verified the extent of the SCC and demonstrated widespread
      brain damage in all animals who exhibited status epilepticus after 72 h. SCC was
      associated with a lesion of hippocampal commissure in 64% of animals in the SCC
      group. This protective effect was not related to lesion of the skull or the
      longitudinal sinus. The lesion of the hippocampal commissure may have contributed
      to the protective effect of SCC, since animals with an isolated lesion of the
      hippocampal commissure without SCC survived the status and showed an increased
      latency to seizure and status epilepticus. These data suggest that the lithium
      pilocarpine model of status epilepticus may be useful in the study of the
      mechanism of efficacy of SCC in the treatment of epilepsy.

PMID- 1396534
TI  - Variability and clinical relevance of the interaction between sodium valproate
      and carbamazepine in epileptic patients.
AB  - Twenty-four epileptic patients (16 females, 8 males; aged 13-62 years) were
      studied before and after the addition of sodium valproate (VPA) 500 mg twice
      daily for 5 days. All had been established previously on carbamazepine (CBZ) as
      monotherapy (300-1600 mg daily in divided doses). Sixteen of these patients
      undertook a battery of cognitive function tests before and after VPA
      introduction. VPA had no effect on total or free CBZ concentrations. However,
      median concentrations of the active metabolite, CBZ 10,11 epoxide (CBZ-E), were
      significantly increased (CBZ-E before VPA 1.3 mg/l, after VPA 2.1 mg/l, P less
      than 0.01). The median rise was 25%, although the extent of the interaction
      ranged from a 25% decrease to an increase of 123% in CBZ-E concentrations. This
      was related to the marked inter-individual variation in circulating VPA (mean 25
      69 mg/l), as CBZ-E concentrations correlated significantly with total (r = 0.5, P
      less than 0.05, 95% CI 0 to +0.08) and free (r = 0.7, P less than 0.001, 95% CI
      +0.09 to +0.25) VPA levels in individual patients. Although uncontrolled, no
      deterioration in performance of any of the cognitive function tests was observed
      following the addition of VPA. This study does not support immediate clinical
      relevance for this drug interaction between VPA and CBZ.

PMID- 1396535
TI  - Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed
      epilepsy: one year follow-up.
AB  - We evaluated the effect of initial oxcarbazepine (OXC) monotherapy on memory,
      attention and simple psychomotor speed in 14 patients; 15 patients with initial
      phenytoin (PHT) monotherapy served as reference patients. Neuropsychological
      assessments were performed before starting the treatment and after 6 and 12
      months follow-up with steady-state drug treatment. Differential cognitive effects
      of OXC and PHT were not apparent in our study. As the efficacy of present
      antiepileptic drugs in adult epilepsy is analogous, the choice of drug is
      determined by the comparative side effects of the drugs. In the present study the
      number of successfully treated patients was similar in both OXC and PHT groups.
      As far as cognitive side effects are concerned our results revealed no evidence
      favoring either antiepileptic over the other.

PMID- 1396536
TI  - Help-seeking strategies for epilepsy by previously untreated patients in northern
      Ecuador.
AB  - Two hundred and fifteen patients with epilepsy and 125 controls were given
      questions designed to elicit their help-seeking strategies for the condition.
      This was part of a large-scale medical intervention study in a rural area of a
      developing country (the provinces of El Carchi and Imbaburra, northern Ecuador).
      Local medical personnel were also surveyed. One hundred and forty-four patients
      and 98 controls were questioned again 12 months after they had been enrolled in
      the intervention programme to see if their attitudes and practices had changed.
      Over the study period, belief in medical remedies, particularly those offered by
      the study, rose significantly among both controls and patients. Control readiness
      to consult local healers for help and belief in their effectiveness also rose,
      whereas patient belief in healer help, already significantly less at baseline
      because of previous negative experiences, had declined still further. Though no
      patients treated were on antiepileptic treatment at baseline, 71% claimed to have
      sought the help of allopathic practitioners at some point in the past, 35% 'many
      times'. Of these only 21% had ever been given antiepileptic drugs; some
      consultations were not at local health facilities. Thirty-two per cent of
      patients also claimed to have consulted traditional healers. The high number of
      patients claiming to visit doctors was not entirely confirmed in the medical
      evidence. Even this source, however, suggested more consulted doctors than
      expected from the observation that only 10% were on any kind of treatment at the
      start of the study (none on antiepileptic drugs).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1396537
TI  - Properties of the convulsive threshold determined by direct cortical stimulation
      in rats.
AB  - The threshold for convulsions in rats can be determined by applying ramp-shaped
      pulse trains directly to the cerebral cortex in rats, which provides a convenient
      model for investigating anticonvulsant drug effects. This study was undertaken to
      extend a previous study on the properties of this model. Analysis of the cortical
      EEG, recorded from two motor areas and one somatosensory area, showed that the
      start of clonic forepaw movement, marking the convulsive threshold, is preceded
      by the appearance of sharp negative spikes at the electrodes in the two motor
      areas. There was a strong linear relation between the clinically determined
      threshold and the EEG derived threshold (r = 0.93, slope 0.99, SD 0.04),
      confirming the validity of the clonic movement threshold as an objective and
      accurate measure. Examination of the seizure patterns seen with various degrees
      of suprathreshold stimulation led to the distinction between a threshold for
      localized and for generalized seizure activity (TLS and TGS respectively).
      Carbamazepine selectively and strongly increased the TGS, whereas it only
      slightly affected the TLS, indicating that cortical stimulation can be used to
      select drugs that specifically prevent seizure spread, for which carbamazepine is
      a prototype. It was found that the TLS was not affected by testing at intervals
      as short as 1 min, provided that no self-sustained seizures were induced.
      However, if the TGS was passed, the TLS was increased substantially for at least
      10 min, while complete recovery could take several hours. The intensity of
      stimulation, rather than seizure duration, appeared to be the determinant for the
      TLS increase. There was no seasonal influence or effect of stimulation electrode
      depth. There may be a minor effect of experience in using the test. It was
      concluded that the observed variability was mainly an intrinsic property of the
      individual animal.

PMID- 1396538
TI  - Regional brain glucose metabolism in patients with complex partial seizures
      investigated by intracranial EEG.
AB  - We performed interictal 18F-2-fluoro-2-deoxy-D-glucose positron emission
      tomography (18FDG-PET) studies in 57 patients with complex partial epilepsy
      (CPE), not controlled by medical treatment and considered for surgical resection
      of their epileptic focus. A precise localization of the epileptic focus was
      obtained in 37 of these patients with a combination of subdural and depth
      electrodes. We visually inspected the metabolic images; we also measured glucose
      consumption in a number of brain regions and compared the values with those
      obtained in 17 normal controls. Eighty-two percent of the 57 patients had an area
      of glucose hypometabolism on the 18FDG-PET images. Six patients had a frontal
      epileptic focus, 3 of them had a frontal lobe hypometabolism. Twenty-six patients
      had a unilateral temporal lobe focus and all of them displayed a temporal lobe
      hypometabolism. The asymmetry was more pronounced in the lateral temporal cortex
      (-20%) than in the mesial part of the temporal lobe (-9.6%). In each cortical
      brain region on the side of the epileptic focus (except the sensorimotor cortex),
      glucose consumption rate was lower than in the contralateral region or than in
      controls. No differences could be found between patients with a seizure onset
      restricted to the hippocampus and patients with a seizure onset involving the
      hippocampus and the adjacent neocortex. Divergent metabolic patterns were
      obtained in 5 patients with bilateral temporal seizure foci. Combined with other
      non invasive techniques (EEG, neuroradiology), PET contributes increasingly to
      the selection of patients with CPE who could benefit from surgical
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396539
TI  - Single photon emission computed tomography using perfusion tracers in seizure
      disorders.
AB  - Single photon emission computed tomography (SPECT) using perfusion tracers makes
      it possible to estimate regional cerebral blood flow (rCBF) and, indirectly,
      local brain metabolism. It may be possible to detect and follow
      physiopathological alterations, such as may be seen in seizure disorders. The
      authors review the principles of and some data on perfusion SPECT in seizure
      disorders, stress advantages as well as major drawbacks and add their initial
      experience with Tc-99m hexamethylpropyleneamine oxime (HMPAO) SPECT in febrile
      convulsions.

PMID- 1396540
TI  - Polyamine metabolism in epileptic cortex.
AB  - Polyamine (tissue) concentrations have been studied in hippocampus and temporal
      neocortex from patients with temporal lobe epilepsy. Depth electrode recordings
      demonstrated hippocampal origin of the seizures, the temporal neocortex being
      involved during the discharge propagation. Neuropathological examination of
      excised tissues showed glial proliferation or glioma in Ammon's horn (CA),
      whereas the temporal neocortex did not exhibit any histological abnormality.
      Polyamine (putrescine or PUT, spermidine or SPD, spermine or SPM) concentrations
      were determined on surgical samples from the hippocampus and various areas of
      temporal neocortex. Human post-mortem tissue from temporal lobe regions was used
      for controls. In post-mortem controls and temporal neocortex specimens from
      epileptic patients, polyamine levels were similar (in nmol/g wet weight: PUT = 40
      100; SPD = 200-350; SPM = 100-200). In CA, polyamine levels exhibited striking
      changes: SPD content was significantly increased (350-700 nmol/g) while SPM was
      lowered (50-100). PUT was only increased in CA invaded by the tumoral process
      (100-180). Accordingly, a very high SPD/SPM molar ratio in the abnormal CA region
      was observed, indicating an acceleration of polyamine neosynthesis which is
      usually related to ornithine decarboxylase induction. Metabolic changes in
      polyamines appear to be selective of human epileptic hippocampus. A relationship
      between glial proliferation (gliosis or neoplasia), epileptic firing and
      polyamines is discussed.

PMID- 1396541
TI  - Aspects of pharmacotherapy in epilepsy.
AB  - Notwithstanding important advances in the treatment of epilepsy basic knowledge
      about the epilepsies and about the mechanism of action of antiepileptic drugs is
      still fragmentary. This statement is illustrated with examples from the
      laboratory and clinical practice. In particular it is emphasized that not only is
      little known about the mechanism of side-effects but also little work appears to
      be in progress to change that situation.

PMID- 1396542
TI  - A brief history of epilepsy and its therapy in the Western Hemisphere.
AB  - The history of epilepsy and its treatment in the western world dates back at
      least 4 millennia to the ancient civilization of the middle east. Past and
      present treatments have been empirical, usually reflecting the prevailing views
      of epilepsy, be they medical, theological or superstitious. Ancient physicians
      relied on clinical observation to distinguish between epileptic syndromes and
      infer their cause. Early pathophysiological theories of epilepsy correctly
      identified the brain as the site of the problem, but emphasized incorrect causes
      such as an excess of phlegm in the brain. Treatments consisted of prescribed
      diets or living conditions, occasional surgery such as bloodletting or skull
      trephination and medicinal herbs. These treatments, often ineffective, had the
      intellectual advantage of being based on pathophysiological principles, unlike
      current, more empirical, therapies. The unfortunate but widely held view of
      epilepsy as being due to occult or evil influences gained adherents even in the
      medical world during ancient times, and the later acceptance of Christianity
      allowed theological interpretations of seizures as well. Magical or religious
      treatments were more frequently prescribed as a result, practices which persist
      to this day. In the Renaissance an attempt was made to view epilepsy as a
      manifestation of physical illness rather than a moral or occult affliction, but
      it was during the Enlightenment that epilepsy was viewed along more modern lines,
      helped by advances in anatomy and pathology and the development of chemistry,
      pharmacy and physiology. The idea that focal irritation may cause seizures came
      about from clinical and experimental work, and was supported by the successful
      control of seizures by the (sedative) bromides and barbiturates in the late 19th
      century. The introduction of phenytoin showed that non-sedative drugs could be
      effective in controlling seizures as well, and the development of in vivo seizure
      models widened the scope of pharmaceutical agents tested for their efficacy
      against epilepsy. Increasing knowledge of the cellular mechanisms of epilepsy
      will, hopefully, allow the development and introduction of drugs with increasing
      specificity against seizure activity and the development of epilepsy.

PMID- 1396543
TI  - Genetic models of absence epilepsy, with emphasis on the WAG/Rij strain of rats.
AB  - In this review, the main characteristics of genetic models of absence epilepsy,
      in particular with respect to WAG/Rij rats, are presented. Genetic models are
      important and relevant, since evidence exists that these models mimic
      spontaneously occurring human epilepsy more than models in which epilepsy is
      artificially induced. Genetic models can be divided into models in which seizures
      are elicited and into those in which epilepsy appears without any sensory
      stimulation. The majority of genetic models show that absence type of epilepsy;
      during the last few years, we and others have noticed that rats of various
      strains exhibit spontaneously occurring spike-wave discharges in the EEG. Among
      the strains highly affected is the WAG/Rij strain, which is a fully inbred
      strain. Individuals are homozygous and because of this property, genetic studies
      are meaningful. Electrophysiological studies have indicated that abnormal
      discharges in the cortical EEG are generalized and that the hippocampus is not
      involved. Parts of the thalamus, together with the thalamic reticular nucleus,
      apparently act as a pacemaker for the abnormal discharges. There is a circadian
      modulation in the number of spike-wave discharges. Discharges mainly occur during
      intermediate levels of vigilance such as passive wakefulness and light slow-wave
      sleep and at transitions of sleep states. Pharmacological studies with clinically
      effective antiepileptic drugs have shown a close agreement in seizure response
      between man and rat. Studies with new compounds have emphasized the role of the
      GABAergic and glutamatergic system in this type of epilepsy. Particularly
      striking is the role of the GABAergic system. GABA agonists enhance and GABA
      antagonists reduce the occurrence of spike-wave discharges, which deviates from
      the effects of GABAergic drugs in non-convulsive epilepsy. Even more striking is
      the role of the benzodiazepines, generally seen as GABA agonists; these drugs do
      not act as such in absence epilepsy since they reduce spike-wave discharges. Also
      good evidence for an involvement of other neurotransmitters such as
      noradrenaline, dopamine and opioid peptides exists in absence epilepsy. Genetic
      data obtained from the WAG/Rij model for absence epilepsy show a relatively
      simple pattern of inheritance with one gene determining whether an individual is
      epileptic or not, and with other genes regulating the number and duration of
      seizures. This is in good agreement with the more restricted human data.
      Cognitive studies have shown two important features of epilepsy in the WAG/Rij
      strain: modulation of the number of spike-wave discharges by mental or physical
      activity and on the other hand, the disruption of cognitive activity by spike
      wave discharges.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1396544
TI  - Chemical models of epilepsy with some reference to their applicability in the
      development of anticonvulsants.
AB  - This paper reviews chemical models of epilepsy and their relevance in the
      identification and characterization of anticonvulsants. For each convulsant we
      discuss possible modes of administration, clinical type(s) of seizures induced,
      proposed mechanism(s) of epileptogenesis and, where available, responsiveness of
      the induced seizures to anticonvulsants. The following compounds are reviewed:
      pentylenetetrazol, bicuculline, penicillin, picrotoxin, beta-carbolines, 3
      mercaptopropionic acid, hydrazides, allylglycine; the glycine antagonist
      strychnine; gamma-hydroxybutyrate; excitatory amino acids (glutamate, aspartate,
      N-methyl-D-aspartate, quisqualate, kainate, quinolinic acid); monosubstituted
      guanidino compounds, metals (alumina, cobalt, zinc, iron); neuropeptides (opioid
      peptides, corticotropin releasing factor, somatostatin, vasopressin); cholinergic
      agents (acetylcholine, acetylcholinesterase inhibitors, pilocarpine); tetanus
      toxin; flurothyl; folates; homocysteine and colchicine. Although there are a
      multitude of chemical models of epilepsy, only a limited number are applied in
      the routine screening of potential anticonvulsants. Some chemical models have a
      predictive value with regard to the clinical profile of efficacy of the tested
      anticonvulsants. Some chemical models may contribute to a better understanding of
      possible mechanisms of epileptogenesis.

PMID- 1396546
TI  - Effects of antiepileptic drugs on 4-aminopyridine-induced epileptiform activity
      in young and adult rat hippocampus.
AB  - Extracellular field potential recordings were used to study the effects of the
      antiepileptic drugs (AEDs) carbamazepine (CBZ), phenytoin (PHT), phenobarbital
      (PhB) and valproic acid (VPA) on the epileptiform activity evoked by 4
      aminopyridine (4-AP, 50 microM) in the CA3 subfield of rat hippocampal slices
      obtained from young (8-23-day-old) and adult (> 60-day-old) male rats. Ictal
      (duration: 3-20 s; rate of occurrence: 3-12 x 10(-3) s-1) and interictal
      (duration: 0.2-0.8 s; rate of occurrence: 0.2-0.8 s-1) discharges were recorded
      in young slices, while only interictal activity (duration: 70-90 ms; rate of
      occurrence: 0.5-0.9 s-1) discharges were observed in adult slices. In addition,
      in both young and adult slices 4-AP disclosed a synchronous long-lasting
      potential (duration and rate of occurrence: 0.6-3 s, 7-70 x 10(-3) s-1 and 260
      660 ms, 8-60 x 10(-3) s-1, respectively) that was caused by the activation of the
      gamma-aminobutyric acid type A (GABAA) receptor. In young slices, ictal
      discharges were blocked by CBZ (0.05 mM), PHT (0.1 mM), PhB (0.5 mM) and VPA (0.5
      mM). With the exception of PhB, higher concentrations were necessary in these
      experiments for blocking the interictal activity (i.e., CBZ: 0.1 mM; PHT: > 0.2
      mM; VPA: 2 mM). At these concentrations, none of the AEDs blocked the interictal
      activity in the adult hippocampus, but only reduced the rate of occurrence. PhB
      enhanced the rate of occurrence of the synchronous GABA-mediated long-lasting
      potentials both in young (increase: 190%) and in adult (increase: 145%) slices,
      while VPA increased their occurrence by 54% only in young slices. CBZ decreased
      the rate of occurrence of this long-lasting potential only in adult hippocampus.
      Our data indicate that the effects of the AEDs on 4-AP-induced epileptiform
      discharges are both pattern- and age-dependent. The rank order of potencies of
      the four AEDs was: (a) in young: CBZ > PHT > PhB > VPA; (b) in adult: CBZ > PhB >
      PHT > VPA.

PMID- 1396545
TI  - Valproic acid treatment of experimental status epilepticus.
AB  - The efficacy of valproic acid (VPA) in control of generalized convulsive status
      epilepticus was tested in a rat model. Rats with cortical cobalt lesions were
      injected with homocysteine thiolactone to induce secondarily generalized tonic
      clonic seizures (GTCS). The median effective dose (ED50) for control of GTCS was
      211.9 mg/kg (270 micrograms/ml in serum 30 min post dose) when treatment was
      given intraperitoneally after the second GTCS. VPA entered both serum and brain
      very rapidly after injection, with little change in concentration from 5 to 30
      min post dose. In earlier experiments with phenytoin, phenobarbital, diazepam and
      lorazepam in this model, we found that the serum concentrations produced by the
      ED50s versus GTCS were very similar to those which have been reported to be
      effective in treating human status epilepticus. If this same relationship holds
      true for VPA, we would predict that a serum concentration of around 270
      micrograms/ml VPA would be required for control of generalized convulsive status
      epilepticus in human patients. The safety of this high a concentration of VPA has
      not been tested.

PMID- 1396547
TI  - Anticonvulsant profile of MDL 27,266: an orally active, broad-spectrum
      anticonvulsant agent.
AB  - The novel anticonvulsant substance MDL 27,266 was tested in a variety of
      anticonvulsant models to assess its anticonvulsant profile, behavioral toxicity
      and oral bioavailability. Intraperitoneally (i.p.) administered MDL 27,266
      afforded complete protection against sound-induced seizures in DBA/2J and Frings
      audiogenic-seizure (AGS)-susceptible mice (ED50s: 5.0 and 5.1 mg/kg,
      respectively). It was also effective following i.p. administration to CF#1 mice
      against maximal electroshock (MES)-, pentetrazole-, picrotoxin-, quisqualic acid
      , and strychnine-induced seizures (ED50s: 24.9, 13.8, 43.3, 8.05, and 60.5 mg/kg,
      respectively). MDL 27,266, in well tolerated oral doses, prevented the expression
      of stage 5 behavioral seizures in the corneal-kindled rat and myoclonic seizures
      in the photosensitive baboon, Papio papio. Chronic administration of MDL 27,266
      to AGS-susceptible mice did not markedly affect its anticonvulsant potency or
      efficacy against sound-induced seizures. These results suggest that MDL 27,266
      possesses a broad anticonvulsant profile which most closely approximates that of
      the broad-spectrum prototype antiepileptic drug valproate.

PMID- 1396548
TI  - Cerebrovascular responses to pentylenetetrazol: time and dose dependent effects.
AB  - The effects of subconvulsant and convulsant doses of pentylenetetrazol (PTZ) on
      cerebral blood flow (rCBF), permeability-capillary surface area products (rPS),
      and brain vascular spaces (BVS) were examined in 15 brain regions at 1 h, 24 h
      and 1 week after injection in male Sprague-Dawley rats. Brain histology was
      examined 3 days after injection. A dose of PTZ (50 mg/kg, i.p.), sufficient to
      trigger a single convulsive seizure, produced small regional changes in rCBF at 1
      h, but not at 24 h or 1 week after injection. No significant changes in rPS or
      BVS were found at any time, and only mild histologic changes were observed. In
      contrast, a dose of PTZ (25 mg/kg) which failed to cause either convulsions or
      significant electrocorticographic changes, markedly increased rCBF and rPS. Some
      of these regional effects were still observed 1 week later. Similarly, more
      severe and extensive cellular changes followed treatment with the subconvulsive
      dose. These findings indicate that PTZ treatment can have prolonged effects on
      cerebrovascular functions and neuronal integrity even in the absence of
      convulsive activity.

PMID- 1396549
TI  - Neuropathological changes during generalized seizures in newborn monkeys.
AB  - The brains of four 2-week-old marmoset monkeys were perfusion-fixed immediately
      after bicuculline-induced seizures lasting 1.5-4.3 h and were later examined by
      light and electron microscopy. Mean arterial blood pressure and rectal
      temperature measurements during seizures did not differ significantly from
      baseline. Plasma glucose concentrations decreased to the 1.5 mM range at the end
      of seizures, and arterial pH and bicarbonate were lower than in control animals,
      although arterial pO2 and pCO2 were maintained. Neuropathological changes were
      minimal. Swollen astrocytic processes surrounded some capillaries and some
      neurons in cerebral cortex, hippocampus, putamen and thalamus. Almost all the
      neurons examined looked normal, but mitochondrial swelling was present in a few.
      All but the most severe mitochondrial swelling, which occurred very rarely in one
      of four animals, is potentially reversible. The virtual absence of neuronal
      necrosis in these neonatal monkeys is consistent with the resistance to seizure
      induced brain damage found in immature rats, and stands in sharp contrast to the
      damage seen in older animals. Lack of neuronal damage, however, does not rule out
      potential adverse effects of prolonged seizure activity on subsequent brain
      growth and development.

PMID- 1396550
TI  - A compound score for estimating the influence of inattention and somnolence
      during the intracarotid amobarbital test.
AB  - Alterations in the level of consciousness may render the interpretation of the
      memory test results from the intracarotid amobarbital procedure difficult. The
      present study was designed to investigate the impact of inattention and
      somnolence on memory performance during the Amytal test. Nineteen consecutive
      patients undergoing the test were investigated. The memory test was constructed
      to comprise two consecutive parts with identical design, so as to make possible
      comparisons over time in the same patients. Reaction level and somnolence were
      continuously assessed during the procedure and a stimulus-task response test to
      evaluate the degree of attention was used. On the basis of these parameters a
      compound 'inattention score' was constructed. The results indicate that
      inattention and somnolence negatively influence memory performance and should be
      taken into account when evaluating the Amytal memory test results. In cases with
      poor memory results high inattention scores may speak in favour of preoperative
      hemisphere memory testing or a repeat injection with reduced Amytal dosage before
      deciding upon the extent of a planned resection. On the other hand, low
      inattention scores together with amnesia for the testing procedure may indicate
      that the memory test results can be relied on.

PMID- 1396551
TI  - Heavy metal tolerance in the fission yeast requires an ATP-binding cassette-type
      vacuolar membrane transporter.
AB  - In response to heavy metal stress, plants and certain fungi, such as the fission
      yeast Schizosaccharomyces pombe, synthesize small metal-binding peptides known as
      phytochelatins. We have identified a cadmium sensitive S. pombe mutant deficient
      in the accumulation of a sulfide-containing phytochelatin-cadmium complex, and
      have isolated the gene, designated hmt1, that complements this mutant. The
      deduced protein sequence of the hmt1 gene product shares sequence identity with
      the family of ABC (ATP-binding cassette)-type transport proteins which includes
      the mammalian P-glycoproteins and CFTR, suggesting that the encoded product is an
      integral membrane protein. Analysis of fractionated fission yeast cell components
      indicates that the HMT1 polypeptide is associated with the vacuolar membrane.
      Additionally, fission yeast strains harboring an hmt1-expressing multicopy
      plasmid exhibit enhanced metal tolerance along with a higher intracellular level
      of cadmium, implying a relationship between HMT1 mediated transport and
      compartmentalization of heavy metals. This suggests that tissue-specific
      overproduction of a functional hmt1 product in transgenic plants might be a means
      to alter the tissue localization of these elements, such as for sequestering
      heavy metals away from consumable parts of crop plants.

PMID- 1396553
TI  - Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor
      cytotoxicity.
AB  - Heat treatment and various other stresses render tumor cells resistant to
      cytotoxicity mediated by tumor necrosis factors (TNFs). Here, we elucidate the
      molecular basis of this phenomenon by demonstrating that the major heat shock
      protein, hsp70, protects tumor cells from TNF cytotoxicity even in the absence of
      stress. The human hsp70 gene was stably introduced into highly TNF-sensitive WEHI
      S tumor cells both in the sense and antisense orientation. All clones
      constitutively expressing the exogenous human hsp70 gene were protected from TNF
      mediated killing approximately 1000-fold. Remarkably, the growth of one clone was
      actually stimulated by low concentrations of TNF. Moreover, a clone expressing
      antisense hsp70 RNA was rendered extremely sensitive to TNFs. Hsp70-mediated
      protection from TNF cytotoxicity was confirmed in transient expression
      experiments employing retroviral vectors. Changes in cellular sensitivity to TNF
      were not associated with alterations in the binding of TNF to its receptors.
      Neither the transfection procedure itself nor overexpression of the low molecular
      weight heat shock protein, hsp27, had any effect on cellular susceptibility to
      TNFs. Our data suggest that hsp70 may increase the oncogenic potential of some
      tumor cells by providing them with an escape mechanism from immunological
      defense.

PMID- 1396552
TI  - Primary and secondary structure of the pore-forming peptide of pathogenic
      Entamoeba histolytica.
AB  - A pore-forming peptide is implicated in the potent cytolytic activity of
      pathogenic Entamoeba histolytica. Using NH2-terminal sequence information of this
      peptide, the corresponding cDNA was isolated. The cDNA-deduced amino acid
      sequence revealed a putative signal peptide and a mature peptide of 77 amino
      acids including six cysteine residues. Computer-aided secondary structure
      analysis predicted that the peptide would be composed of four adjacent alpha
      helices, and CD spectroscopy indicated an all alpha-helical conformation. The
      tertiary structure appears to be stabilized by three disulfide bonds; the pore
      forming activity was not sensitive to heat but was lost in the presence of
      reducing agents. Sequence homology was found to the saposins and to surfactant
      associated protein B, both mammalian polypeptides of similar size and secondary
      structure but of non-lytic function. In particular, the six cysteine residues
      were found to be conserved, suggesting a common motif for stabilizing a
      favourable tertiary structure. Compared with previously characterized toxic
      peptides also containing three disulfide bonds, the amoeba peptide may represent
      a distinct class of biologically active peptides.

PMID- 1396554
TI  - Interaction of heat-shock protein 70 with p53 translated in vitro: evidence for
      interaction with dimeric p53 and for a role in the regulation of p53
      conformation.
AB  - In intact cells, hsp70 proteins selectively complex with mutant p53. We report
      here that rabbit reticulocyte lysate contains hsp70 which selectively complexes
      with the mutant p53 translated in vitro. Hsp70 complexes with dimers and possibly
      monomers of p53 in a manner that requires the terminal 28 amino acids of p53.
      Using murine p53Val135, which is temperature-sensitive for phenotype, we
      demonstrate that p53-hsp70 complexes can occur after post-translational switching
      from wild-type to mutant p53 phenotype. Moreover, the temperature-induced switch
      of full-length p53Val135 from wild-type to mutant phenotype is ATP-independent,
      whereas the switch from mutant to wild-type form requires ATP hydrolysis and
      involves hsp70. These results imply that hsp70 is involved in the regulation of
      p53 conformation.

PMID- 1396555
TI  - Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3
      and IL-5 receptors for growth signal transduction and tyrosine phosphorylation.
AB  - The high-affinity receptors for human granulocyte-macrophage colony-stimulating
      factor (GM-CSF), interleukin 3 (IL-3) and interleukin 5 (IL-5) are composed of
      two distinct subunits, alpha and beta c. The alpha subunits are specific for each
      cytokine, whereas the beta subunit (beta c) is shared by the three receptors and
      is an essential component of signal transduction. We have made a series of mutant
      beta c cDNAs that delete various regions of the cytoplasmic domain and examined
      the function of these mutants by coexpressing them with the alpha subunit of the
      human GM-CSF receptor (hGMR) in an IL-3-dependent mouse pro-B cell line BaF3. Two
      domains in the membrane-proximal portion of beta c were found to be important for
      transducing the hGM-CSF-mediated growth signals: one domain between Arg456 and
      Phe487 appears to be essential for proliferation, and the second domain between
      Val518 and Asp544 enhances the response to GM-CSF, but is not absolutely required
      for proliferation. The region between Val518 and Leu626 was responsible for major
      tyrosine phosphorylation of 95 and 60 kDa proteins. Thus, beta c-mediated major
      tyrosine phosphorylation of these proteins was apparently separated from
      proliferation. However, the beta 517 mutant lacking residues downstream of Val518
      transmitted a herbimycin-sensitive proliferation signal, suggesting that beta 517
      still activates a tyrosine kinase(s). We also evaluated the role of the
      cytoplasmic domain of the GMR alpha subunit and the results suggest that it is
      involved in the hGM-CSF-mediated signal transduction, but is not
      essential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396556
TI  - Signal transduction between enteropathogenic Escherichia coli (EPEC) and
      epithelial cells: EPEC induces tyrosine phosphorylation of host cell proteins to
      initiate cytoskeletal rearrangement and bacterial uptake.
AB  - Upon attachment to cultured HeLa cells, enteropathogenic Escherichia coli (EPEC)
      induces assembly of a complex cytoskeletal structure within the eucaryotic cell,
      localized beneath the adherent bacterium. In addition, EPEC induces its own
      internalization by non-phagocytic epithelial cells. We found that after binding
      to the epithelial cell surface, EPEC induces tyrosine phosphorylation of three
      eucaryotic proteins. The major phosphorylation substrate is a 90 kDa protein
      (Hp90). In correlation with Hp90 tyrosine phosphorylation, the EPEC-induced
      cytoskeletal structure also contained tyrosine phosphorylated proteins. Using
      tyrosine protein kinase inhibitors and EPEC mutants (cfm) that fail to induce
      Hp90 phosphorylation, we demonstrate that induction of Hp90 phosphorylation is
      involved in initiation of the cytoskeletal structure assembly and in bacterial
      uptake. Other non-invasive EPEC mutants (eae) are still able to induce Hp90
      tyrosine phosphorylation and to initiate aggregation of the tyrosine
      phosphorylated proteins and some cytoskeleton components. However, eae mutants
      are deficient in nucleating the aggregates into an organized structure.

PMID- 1396557
TI  - Substrate inhibition of acetylcholinesterase: residues affecting signal
      transduction from the surface to the catalytic center.
AB  - Amino acids located within and around the 'active site gorge' of human
      acetylcholinesterase (AChE) were substituted. Replacement of W86 yielded inactive
      enzyme molecules, consistent with its proposed involvement in binding of the
      choline moiety in the active center. A decrease in affinity to propidium and a
      concomitant loss of substrate inhibition was observed in D74G, D74N, D74K and
      W286A mutants, supporting the idea that the site for substrate inhibition and the
      peripheral anionic site overlap. Mutations of amino acids neighboring the active
      center (E202, Y337 and F338) resulted in a decrease in the catalytic and the
      apparent bimolecular rate constants. A decrease in affinity to edrophonium was
      observed in D74, E202, Y337 and to a lesser extent in F338 and Y341 mutants.
      E202, Y337 and Y341 mutants were not inhibited efficiently by high substrate
      concentrations. We propose that binding of acetylcholine, on the surface of AChE,
      may trigger sequence of conformational changes extending from the peripheral
      anionic site through W286 to D74, at the entrance of the 'gorge', and down to the
      catalytic center (through Y341 to F338 and Y337). These changes, especially in
      Y337, could block the entrance/exit of the catalytic center and reduce the
      catalytic efficiency of AChE.

PMID- 1396558
TI  - Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release
      and protease activity depend on zinc.
AB  - Tetanus and botulinum neurotoxins are the most potent toxins known. They bind to
      nerve cells, penetrate the cytosol and block neurotransmitter release. Comparison
      of their predicted amino acid sequences reveals a highly conserved segment that
      contains the HexxH zinc binding motif of metalloendopeptidases. The metal content
      of tetanus toxin was then measured and it was found that one atom of zinc is
      bound to the light chain of tetanus toxin. Zinc could be reversibly removed by
      incubation with heavy metal chelators. Zn2+ is coordinated by two histidines with
      no involvement in cysteines, suggesting that it plays a catalytic rather than a
      structural role. Bound Zn2+ was found to be essential for the tetanus toxin
      inhibition of neurotransmitter release in Aplysia neurons injected with the light
      chain. The intracellular activity of the toxin was blocked by phosphoramidon, a
      very specific inhibitor of zinc endopeptidases. Purified preparations of light
      chain showed a highly specific proteolytic activity against synaptobrevin, an
      integral membrane protein of small synaptic vesicles. The present findings
      indicate that tetanus toxin, and possibly also the botulinum neurotoxins, are
      metalloproteases and that they block neurotransmitter release via this protease
      activity.

PMID- 1396559
TI  - Developmental modification of lipophosphoglycan during the differentiation of
      Leishmania major promastigotes to an infectious stage.
AB  - Protozoan parasites of the genus Leishmania produce the novel surface
      glycoconjugate, lipophosphoglycan (LPG), which is required for parasite
      infectivity. In this study we show that LPG structure is modified during the
      differentiation of L. major promastigotes from a less infectious form in
      logarithmic growth phase to a highly infectious 'metacyclic' form during
      stationary growth phase. In both stages, the LPGs comprise linear chains of
      phosphorylated oligosaccharide repeat units which are anchored to the membrane
      via a glycosyl-phosphatidylinositol glycolipid anchor. During metacyclogenesis
      there is (i) an approximate doubling in the average number of repeat units per
      molecule from 14 to 30, (ii) a pronounced decrease in the relative abundance of
      repeat units with side chains of beta Gal or Gal beta 1-3Gal beta 1-, and a
      corresponding increase in repeat units with either no side chains or with side
      chains of Arap alpha 1-2 Gal beta 1- and (iii) a decrease in the frequency with
      which the glycolipid anchor is substituted with a single glucose alpha 1
      phosphate residue. While the majority of the LPG phosphoglycan chains are capped
      with the neutral disaccharide, Man alpha 1-2Man, a significant minority of the
      chains appeared to terminate in non-phosphorylated repeat units and may represent
      incompletely capped species. We suggest that the developmental modification of
      LPG may be important in modulating the binding of promastigotes to receptors in
      the sandfly midgut and on human macrophages and in increasing the resistance of
      metacyclic promastigotes to complement-mediated lysis.

PMID- 1396560
TI  - A novel antifolate resistance gene on the amplified H circle of Leishmania.
AB  - In several Leishmania spp., resistance to methotrexate and other drugs is often
      associated with amplification of the chromosomal H region in the form of
      extrachromosomal H circles. We report here that the H circle of Leishmania
      tarentolae contains an 867 bp open reading frame, ltdh, which mediates high
      levels of resistance to methotrexate and other antifolates, after transfection.
      The predicted amino acid sequence of the ltdh gene product has significant
      similarities to a family of short-chain dehydrogenases, enzymes that are involved
      in several oxido-reduction reactions in a wide range of organisms. To resist
      antifolates, Leishmania amplifies the ltdh gene as part of the H circle. We
      propose that LTDH might be involved in an alternative pathway for the synthesis
      of reduced folates and that ltdh overproduction represents a novel mechanism for
      resistance to antifolates. Our results support the hypothesis that the H region
      of the Leishmania genome contains several drug resistance genes and that
      preferential amplification of this region has evolved as a defense mechanism
      against cytotoxic drugs.

PMID- 1396561
TI  - Bos1p, a membrane protein required for ER to Golgi transport in yeast, co
      purifies with the carrier vesicles and with Bet1p and the ER membrane.
AB  - BOS1 and BET1 are required for transport from the ER to the Golgi complex in
      yeast and genetically interact with each other and a subset of the other genes,
      whose products function at this stage of the secretory pathway. In a previous
      study, we reported that BOS1 encodes a putative 27 kDa membrane protein. Here we
      show that BET1 is structurally similar to the synaptobrevins and identical to the
      SLY12 gene product. Overexpression of SLY12 compensates for the loss of function
      of the ras-like GTP-binding protein Ypt1. Both Bos1p and Bet1p are
      cytoplasmically oriented membrane proteins. Bos1p co-purifies with the ER to
      Golgi transport vesicles and co-fractionates with Bet1p and the ER membrane.

PMID- 1396563
TI  - DNA transcription and repressor binding affect deletion formation in Escherichia
      coli plasmids.
AB  - Chimeric plasmids containing phage M13 and plasmid pBR322 sequences undergo
      deletions in Escherichia coli with a high frequency. In all plasmids one deletion
      endpoint is the M13 replication origin nick site. We examined the effects of
      transcription on the position of the other deletion end-point, by inserting in
      the plasmids an inducible promoter followed by a transcription terminator.
      Transcription dramatically affected deletions in an orientation-dependent way,
      such that greater than 95% of end-points were localized downstream from the
      inserted promoter when it faced the major plasmid transcripts. The end-points
      were not constrained to the transcribed region and were not affected by the
      orientation of pBR322 DNA replication. We propose that deletion events occur
      preferentially in a plasmid domain which is rendered positively supercoiled by
      convergent transcription. We also show that interaction of LacI repressor with
      the cognate operator generates a localized deletion hot spot. This hot spot is
      dependent on pBR322 replication, and therefore probably acts by arresting
      progression of DNA replication.

PMID- 1396562
TI  - MPI1, an essential gene encoding a mitochondrial membrane protein, is possibly
      involved in protein import into yeast mitochondria.
AB  - To identify components of the mitochondrial protein import pathway in yeast, we
      have adopted a positive selection procedure for isolating mutants disturbed in
      protein import. We have cloned and sequenced a gene, termed MPI1, that can rescue
      the genetic defect of one group of these mutants. MPI1 encodes a hydrophilic 48.8
      kDa protein that is essential for cell viability. Mpi1p is a low abundance and
      constitutively expressed mitochondrial protein. Mpi1p is synthesized with a
      characteristic mitochondrial targeting sequence at its amino-terminus, which is
      most probably proteolytically removed during import. It is a membrane protein,
      oriented with its carboxy-terminus facing the intermembrane space. In cells
      depleted of Mpi1p activity, import of the precursor proteins that we tested thus
      far, is arrested. We speculate that the Mpi1 protein is a component of a
      proteinaceous import channel for translocation of precursor proteins across the
      mitochondrial inner membrane.

PMID- 1396564
TI  - Trans regulation in the Ultrabithorax gene of Drosophila: alterations in the
      promoter enhance transvection.
AB  - We report a genetic and molecular study of UbxMX6 and Ubx195rx1, two mutations in
      the Ultrabithorax (Ubx) locus which appear to have a strong effect on the
      activity of the homologous Ubx gene. These mutations show the characteristic
      embryonic and adult phenotypes of Ubx null alleles, and also fail to produce any
      detectable Ubx product. Yet, genetic and phenotypic analyses involving a large
      number of trans heterozygous combinations of UbxMX6 and Ubx195rx1 with different
      classes of Ubx mutations, indicate that they hyperactivate the homologous gene.
      This effect is induced on wildtype or mutant forms of Ubx, provided that the
      pairing in the bithorax region is normal, i.e. these mutations have a strong
      positive effect on transvection. We also show that, unlike all the other known
      cases of transvection in Ubx, this is not zeste-dependent. Southern analyses
      indicate that UbxMX6 is a 3.4 kb deletion, and Ubx195rx1 is an approximately 11
      kb insertion of foreign DNA, both in the promoter region. We speculate that the
      region altered in the mutations may have a wildtype function to ensure cis
      autonomy of the regulation of Ubx transcription.

PMID- 1396565
TI  - Mouse rRNA gene transcription factor mUBF requires both HMG-box1 and an acidic
      tail for nucleolar accumulation: molecular analysis of the nucleolar targeting
      mechanism.
AB  - RNA polymerase I requires at least two nucleolar transcription factors, UBF and
      SL-1, for ribosomal RNA gene (rDNA) transcription. UBF requires SL-1 for the
      formation of a stable initiation complex on the rDNA promoter region. We have
      determined the region of mouse UBF (mUBF) required for nucleolar targeting.
      Although mUBF has a nuclear localization sequence, this sequence alone is not
      sufficient for mUBF to accumulate in the nucleolus. Deletion analyses show that
      mUBF requires a wide region except for the N-terminal 101 amino acids for
      nucleolar targeting. Deletion of either the HMG-box1, a region crucial for rDNA
      binding, or the acidic tail, a region that may interact with SL-1, results in the
      loss of nucleolar targeting. We show by DNA affinity analysis that the HMG-box1
      is absolutely necessary for mUBF to bind to the upstream control element of the
      rDNA. We also show that mUBFs with various internal deletions retain both
      nucleolar targeting and DNA binding ability. A clear correlation was demonstrated
      between the DNA binding and nucleolar targeting ability. These results suggest
      that UBF is transferred to the nucleus by its NLS and is sequestered in the
      nucleolus by its specific and stable binding to the rDNA promoter via HMG-boxes
      and the acidic tail.

PMID- 1396566
TI  - An SRY-related gene expressed during spermatogenesis in the mouse encodes a
      sequence-specific DNA-binding protein.
AB  - SRY, the testis determining gene, encodes a member of a family of DNA binding
      proteins characterized by an amino acid sequence motif known as the HMG box.
      Using degenerate primers and the polymerase chain reaction, we have isolated SRY
      related cDNAs from adult murine testis RNA. One of these, Sox-5, encodes a 43 kDa
      HMG-box protein with similarities to transcription activating proteins. Anti-Sox
      5 antibody was used to analyse expression of Sox-5 in pre-pubertal testis and in
      fractionated spermatogenic cells. Sox-5 is restricted to post-meiotic germ cells,
      being found at highest levels in round spermatids. Sox-5 is a DNA binding protein
      and binding site selection assays suggest that it can bind specifically to
      oligonucleotides containing the consensus motif AACAAT. Sry can also bind to this
      motif, indicating that the Sry family may have overlapping sequence
      specificities.

PMID- 1396569
TI  - Coding from a distance: dissection of the mRNA determinants required for the
      incorporation of selenocysteine into protein.
AB  - Incorporation of selenocysteine into proteins is directed by specifically
      'programmed' UGA codons. The determinants for recognition of the selenocysteine
      codon have been investigated by analysing the effect of mutations in fdhF, the
      gene for formate dehydrogenase H of Escherichia coli, on selenocysteine
      incorporation. It was found that selenocysteine was also encoded when the UGA
      codon was replaced by UAA and UAG, provided a proper codon-anticodon interaction
      was possible with tRNA(Sec). This indicates that none of the three termination
      codons can function as efficient translational stop signals in that particular
      mRNA position. The discrimination of the selenocysteine 'sense' codon from a
      regular stop codon has previously been shown to be dependent on an RNA secondary
      structure immediately 3' of the UGA codon in the fdhF mRNA. It is demonstrated
      here that the correct folding of this structure as well as the existence of
      primary sequence elements located within the loop portion at an appropriate
      distance to the UGA codon are absolutely required. A recognition sequence can be
      defined which mediates specific translation of a particular codon inside an mRNA
      with selenocysteine and a model is proposed in which translation factor SELB
      interacts with this recognition sequence, thus forming a quaternary complex at
      the mRNA together with GTP and selenocysteyl-tRNA(Sec).

PMID- 1396568
TI  - A yeast splicing factor is localized in discrete subnuclear domains.
AB  - Digital imaging microscopy has been used to visualize the splicing protein PRP6p
      and three other yeast nuclear proteins. The results show that PRP6p is uniquely
      localized to discrete subnuclear regions. A combination of cytological and
      biochemical assays suggests that these sites can be saturated when the protein is
      overexpressed and likely correspond to the location of U4/U6 snRNPs. The
      observations indicate that some splicing components are located in discrete
      subregions of the yeast nucleus, similar to the situation described for the
      mammalian nucleus.

PMID- 1396567
TI  - Roles of PRP8 protein in the assembly of splicing complexes.
AB  - Three different approaches have been used to investigate the roles of the yeast
      U5 snRNP protein PRP8 in spliceosome assembly: genetic depletion of PRP8 protein
      in vivo, heat inactivation of temperature-sensitive prp8 protein in protoplasts
      and inhibition of PRP8 function with antibodies in vitro. In each case, U5 and
      U4/U6 snRNPs failed to assemble into the forming spliceosomes. In addition,
      extract prepared from PRP8-depleted cells and extract containing inactivated PRP8
      protein had substantially reduced amounts of U4/U6.U5 triple snRNP complexes.
      Thus, functional PRP8 protein is required for the stable formation of U4/U6.U5
      complexes without which spliceosomes fail to form. As spliceosome formation was
      also blocked by anti-PRP8 antibodies that apparently do not disrupt triple
      snRNPs, PRP8 protein may play a separate role in the assembly of triple snRNPs
      into spliceosomes. As a consequence of PRP8 depletion the levels of the U4, U5
      and U6 snRNAs declined dramatically. We discuss this in the context of the known
      genetic interactions between PRP8 and putative RNA helicase (DEAD box protein)
      genes and propose that PRP8 protein plays a role in regulating dynamic RNA-RNA
      interactions in spliceosome assembly, possibly ensuring the correct
      directionality of these events.

PMID- 1396570
TI  - Mutations in T7 RNA polymerase that support the proposal for a common polymerase
      active site structure.
AB  - In order to test the proposal that most nucleotide polymerases share a common
      active site structure and folding topology, we have generated 22 mutations of
      residues within motifs A, B and C of T7 RNA polymerase (RNAP). Characterization
      of these T7 RNAP mutants showed the following: (i) most of the mutations resulted
      in moderate to drastic reductions in T7 RNAP transcriptional activity supporting
      the idea that motifs A, B and C identify part of the polymerase active site; (ii)
      the degree of conservation of an amino acid within these motifs correlated with
      the degree to which mutation of that amino acid reduced transcriptional activity,
      supporting the predictive ability of this alignment in identifying the most
      functionally critical residues; (iii) a comparison of DNAP I and T7 RNAP mutants
      revealed similarities (as well as differences) between corresponding mutant
      phenotypes; (iv) the Klenow fragment structure is shown to provide a reasonable
      basis for interpretation of the differential effects of mutating different amino
      acids within motifs A, B and C in T7 RNAP. These observations support the
      proposal that these polymerase active sites have similar three-dimensional
      structures.

PMID- 1396571
TI  - Alternating d(G-A) sequences form a parallel-stranded DNA homoduplex.
AB  - The oligonucleotides d[(G-A)7G] and d[(G-A)12G] self-associate under
      physiological conditions (10 mM MgCl2, neutral pH) into a stable double-helical
      structure (psRR-DNA) in which the two polypurine strands are in a parallel
      orientation in contrast to the antiparallel disposition of conventional B-DNA. We
      have characterized psRR-DNA by gel electrophoresis, UV absorption, vacuum UV
      circular dichroism, monomer-excimer fluorescence of oligonucleotides end-labelled
      with pyrene, and chemical probing with diethyl pyrocarbonate and dimethyl
      sulfate. The duplex is stable at pH 4-9, suggesting that the structure is
      compatible with, but does not require, protonation of the A residues. The data
      support a model derived from force-field analysis in which the parallel-stranded
      d(G-A)n helix is right-handed and constituted of alternating, symmetrical
      Gsyn.Gsyn and Aanti.Aanti base pairs with N1H...O6 and N6H...N7 hydrogen bonds,
      respectively. This dinucleotide structure may be the source of a negative peak
      observed at 190 nm in the vacuum UV CD spectrum, a feature previously reported
      only for left-handed Z-DNA. The related sequence d[(GAAGGA)4G] also forms a
      parallel-stranded duplex but one that is less stable and probably involves a
      slightly different secondary structure. We discuss the potential intervention of
      psRR-DNA in recombination, gene expression and the stabilization of genomic
      structure.

PMID- 1396574
TI  - Trypanosoma brucei glycosomal glyceraldehyde-3-phosphate dehydrogenase genes are
      stage-regulated at the transcription level.

PMID- 1396572
TI  - Zuotin, a putative Z-DNA binding protein in Saccharomyces cerevisiae.
AB  - A putative Z-DNA binding protein, named zuotin, was purified from a yeast nuclear
      extract by means of a Z-DNA binding assay using [32P]poly(dG-m5dC) and
      [32P]oligo(dG-Br5dC)22 in the presence of B-DNA competitor. Poly(dG-Br5dC) in the
      Z-form competed well for the binding of a zuotin containing fraction, but salmon
      sperm DNA, poly(dG-dC) and poly(dA-dT) were not effective. Negatively supercoiled
      plasmid pUC19 did not compete, whereas an otherwise identical plasmid pUC19(CG),
      which contained a (dG-dC)7 segment in the Z-form was an excellent competitor. A
      Southwestern blot using [32P]poly(dG-m5dC) as a probe in the presence of MgCl2
      identified a protein having a molecular weight of 51 kDa. The 51 kDa zuotin was
      partially sequenced at the N-terminal and the gene, ZUO1, was cloned, sequenced
      and expressed in Escherichia coli; the expressed zuotin showed similar Z-DNA
      binding activity, but with lower affinity than zuotin that had been partially
      purified from yeast. Zuotin was deduced to have a number of potential
      phosphorylation sites including two CDC28 (homologous to the human and
      Schizosaccharomyces pombe cdc2) phosphorylation sites. The hexapeptide motif
      KYHPDK was found in zuotin as well as in several yeast proteins, DnaJ of E.coli,
      csp29 and csp32 proteins of Drosophila and the small t and large T antigens of
      the polyoma virus. A 60 amino acid segment of zuotin has similarity to several
      histone H1 sequences. Disruption of ZUO1 in yeast resulted in a slow growth
      phenotype.

PMID- 1396573
TI  - Characterization of the bacteriophage lambda excisionase (Xis) protein: the C
      terminus is required for Xis-integrase cooperativity but not for DNA binding.
AB  - We have performed a mutational analysis of the xis gene of bacteriophage lambda.
      The Xis protein is 72 amino acids in length and required for excisive
      recombination. Twenty-six mutants of Xis were isolated that were impaired or
      deficient in lambda excision. Mutant proteins that contained amino acid
      substitutions in the N-terminal 49 amino acids of Xis were defective in excisive
      recombination and were unable to bind DNA. In contrast, one mutant protein
      containing a leucine to proline substitution at position 60 and two truncated
      proteins containing either the N-terminal 53 or 64 amino acids continued to bind
      lambda DNA, interact cooperatively with FIS and promote excision. However, these
      three mutants were unable to bind DNA cooperatively with Int. Cooperativity
      between wild-type Xis and Int required the presence of FIS, but not the Int core
      type binding sites. This study shows that Xis has at least two functional domains
      and also demonstrates the importance of the cooperativity in DNA binding of FIS,
      Xis and Int in lambda excision.

PMID- 1396575
TI  - The cooperative binding of fructose-1,6-bisphosphate to yeast pyruvate kinase.
AB  - The cooperative binding of the allosteric activator fructose-1,6-bisphosphate
      [Fru(1,6)P2] to yeast pyruvate kinase was investigated by equilibrium dialysis
      and fluorescence quench titration. The results show that yeast pyruvate kinase
      binds four molecules of Fru(1,6)P2 per tetramer and the observed fluorescence
      quench follows the binding of the ligand and not the cooperative T to R state
      transition. Additionally it is shown that the binding of Fru(1,6)P2 to yeast
      pyruvate kinase is compatible with the model of cooperativity that has been
      proposed and incorporates an intermediate state, R', with properties between
      those of the T and R states.

PMID- 1396576
TI  - Relatedness of penicillin-binding protein 1a genes from different clones of
      penicillin-resistant Streptococcus pneumoniae isolated in South Africa and Spain.
AB  - Penicillin-resistant strains of Streptococcus pneumoniae have been common in
      South Africa and Spain for several years. Multilocus enzyme electrophoresis
      identified one clone of capsular type 6B which was prevalent in Spain and another
      clone of type 23F that was present in both countries. Genes for penicillin
      binding proteins (PBPs) in penicillin-resistant strains are often mosaics where
      parts of the pneumococcal genes are replaced by homologous genes from other
      species. We have compared the mosaic structures of the PBP 1a genes from the two
      clones as well as from genetically distinct South African isolates. Four classes
      of mosaic PBP 1a genes were found that contained blocks of sequences divergent by
      6-22% from those of sensitive genes; two classes contained sequences coming from
      more than one external source. Data are presented showing that the PBP 1a genes
      from the 23F and the 6B clone are related, and that the two PBP 1a genes from the
      South African isolates are also related. We suggest that the type 23F clone
      originated in Spain prior to distribution into other continents.

PMID- 1396577
TI  - Only some members of a gene family in Trypanosoma cruzi encode proteins that
      express both trans-sialidase and neuraminidase activities.
AB  - Trypomastigotes, the blood stage form of the human parasite Trypanosoma cruzi,
      contain an enzyme on their surface, trans-sialidase, which catalyses the transfer
      of sialic acid from host glycoconjugates to acceptors on its own cell surface. At
      least a subset of the sialic acid-bearing acceptor molecules are involved in
      parasite invasion of host cells, an essential step in the life cycle of the
      parasite. Another trypomastigote surface enzyme that affects host cell invasion
      is neuraminidase and recent evidence suggests that both trans-sialidase and
      neuraminidase activities may be expressed by the same proteins on the parasite
      surface. We describe here the isolation and expression of several members of a
      trans-sialidase--neuraminidase gene family from T.cruzi. One of the isolated
      genes does indeed encode a protein with both trans-sialidase and neuraminidase
      activities, while other members of the gene family encode closely related
      proteins that express neither enzymatic activity. Chimeric protein constructs
      combining different portions of active and inactive genes identified a region of
      the gene necessary for enzymatic activity. Sequence analysis of this portion of
      the gene revealed a limited number of amino acid differences between the
      predicted active and inactive gene products.

PMID- 1396578
TI  - Involvement of a neutral glycolipid in differential cell adhesion in the Xenopus
      blastula.
AB  - Many different molecular species mediate cell adhesion during embryonic
      development. These can have either protein or carbohydrate functional groups,
      which can act in either a homophilic or a heterophilic manner, and often in
      concert. We report here that a monoclonal antibody, M4B, raised against Xenopus
      blastomere membranes, inhibits the calcium-dependent adhesion of dissociated
      blastomeres. M4B maintains its inhibitory effect on adhesion when converted into
      univalent fragments, and specifically affects calcium-dependent adhesion. The
      antigen is regulated in both space and time during early development. It is found
      on cell surfaces throughout the egg to blastula stages, but is more concentrated
      on cells in the animal and marginal zones of the blastula. It is dramatically
      downregulated during gastrulation, and becomes largely restricted to gut
      epithelium by the larval stages. We show also that M4B function is spatially
      differentiated at the blastula stage, since it inhibits the aggregation of
      dissociated animal cells to a greater extent than vegetal cells. This membrane
      antigen may therefore play a role in the differential adhesion observed between
      different regions of the blastula, and which we presume to underlie the
      segregation of the primary germ layers during gastrulation. M4B recognizes a
      complex of plasma membrane glycolipids. Periodate treatment destroys the ability
      of these glycolipids to react with the antibody, indicating that the epitope
      resides in the carbohydrate moiety of the glycolipids. Chemical characterization
      shows that it is a neutral glycolipid, and that the major component is of the
      glycoglycerolipid, rather than the more common glycosphingolipid class. Blocking
      experiments with oligosaccharides of defined structure, and antibody
      crossreactivity show that the M4B antibody does not recognize several known
      embryonic carbohydrate antigens. These results demonstrate that M4B antibody
      recognizes a novel group of developmentally regulated glycolipids which function
      in calcium-dependent cell--cell adhesion in the Xenopus blastula.

PMID- 1396579
TI  - Molecular analysis of mutations in the Caenorhabditis elegans collagen gene dpy
      7.
AB  - Collagens are a family of proteins contributing to the body structure of
      eukaryotes. They are encoded by a large and diverse gene family in the nematode
      Caenorhabditis elegans but by only a few genes in vertebrates. We have studied
      mutant alleles of the C. elegans dpy-7 gene, one of a large group of genes whose
      mutant phenotype is altered body form and several of which have previously been
      shown to encode cuticular collagens. We made use of the C. elegans physical map
      to screen specifically for collagen genes in the region of the X chromosome to
      which dpy-7 maps. This yielded a wild-type collagen gene clone which we showed,
      by micro-injection, could repair the dpy-7 mutant phenotype in transgenic
      animals. We cloned the homologous sequence from four dpy-7 mutant strains and by
      sequence analysis identified a single mutation in each case. All four mutations
      result in the substitution of a glycine with a larger residue in the conserved
      Gly-X-Y collagen domains. Similar substitutions in vertebrate collagens cause the
      heritable brittle bone disorder osteogenesis imperfecta. Whereas the human
      mutations are dominant, the dpy-7 mutations are recessive, and this may reflect
      different levels of complexity of collagenous macromolecular structures in the
      two organisms.

PMID- 1396580
TI  - Analysis of alpha 1 beta 1, alpha 2 beta 1 and alpha 3 beta 1 integrins in cell-
      collagen interactions: identification of conformation dependent alpha 1 beta 1
      binding sites in collagen type I.
AB  - Integrins can mediate the attachment of cells to collagen type I. In the present
      study we have investigated the possible differences in collagen type I
      recognition sites for the alpha 1 beta 1 and alpha 2 beta 1 integrins. Different
      cyanogen bromide (CB) fragments of the alpha 1 (I) collagen chain were used in
      cell attachment experiments with three rat cell types, defined with regard to
      expression of collagen binding integrins. Primary rat hepatocytes expressed alpha
      1 beta 1, primary rat cardiac fibroblasts alpha 1 beta 1 and alpha 2 beta 1, and
      Rat-1 cells only alpha 2 beta 1. All three cell types expressed alpha 3 beta 1
      but this integrin did not bind to collagen--Sepharose or to immobilized collagen
      type I in a radioreceptor assay. Hepatocytes and cardiac fibroblasts attached to
      substrata coated with alpha 1(I)CB3 and alpha 1(I)CB8; Rat-1 cells attached to
      alpha 1(I)CB3 but only poorly to alpha 1(I)CB8-coated substrata. Cardiac
      fibroblasts and Rat-1 cells spread and formed beta 1-integrin-containing focal
      adhesions when grown on substrata coated with native collagen or alpha 1(I)CB3;
      focal adhesions were also detected in cardiac fibroblasts cultured on alpha
      1(I)CB8. The rat alpha 1 specific monoclonal antibody 3A3 completely inhibited
      hepatocyte attachment to alpha 1(I)CB3 and alpha 1(I)CB8, as well as the
      attachment of cardiac fibroblasts to alpha 1(I)CB8, but only partially inhibited
      the attachment of cardiac fibroblasts to alpha 1(I)CB3. 3A3 IgG did not inhibit
      the attachment of Rat-1 cells to collagen type I or to alpha 1(I)CB3.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396581
TI  - Jurkat T cells express a functional neutral endopeptidase activity (CALLA)
      involved in T cell activation.
AB  - We have characterized a T lymphocyte endopeptidase activity that hydrolyses
      succinyl-alanine-alanine-phenylalanine-paranitroanilide (Suc-Ala-Ala-Phe-pNa).
      Hydrolysis of this substrate by intact Jurkat T cells was markedly enhanced when
      exogenous aminopeptidase N was added to the incubation medium. It thus appears
      that the release of paranitroaniline from Suc-Ala-Ala-Phe-pNA results from the
      combination of two distinct enzymatic activities: (i) an endopeptidase activity
      that cleaves the substrate at the alanyl bond and (ii) an aminopeptidase activity
      that ultimately cleaves the phenylalanyl bond. This cleavage was further
      confirmed by HPLC analysis. Specific endopeptidase 24.11 inhibitors were shown to
      inhibit the endopeptidase activity. These features are reminiscent of the
      characteristics of neutral endopeptidase (NEP, also known as endopeptidase 24.11,
      CALLA or CD10). Anti-CD10 monoclonal antibodies (mAbs) recognized the CD10+ B
      cell line Raji, but not Jurkat cells as assessed by FACS analysis. This is
      probably due to a lack of sensitivity of this method, the level of NEP activity
      in Jurkat T cells being 3-5% of that measured in B cell lines. Anti-CD10 mAbs
      immunoprecipitated endopeptidase 24.11 activities in both Jurkat T cells and Raji
      B cells, demonstrating that T lymphocytes express a CALLA-related endopeptidase.
      We also demonstrate that T and B cell endopeptidases have the same molecular
      weight, that T cells express less functional CALLA mRNA than B cells and that
      there are at least two shorter transcripts (1.8 and 0.8 kb) in both T and B
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396582
TI  - Induced expression of PD-1, a novel member of the immunoglobulin gene
      superfamily, upon programmed cell death.
AB  - The classical type of programmed cell death is characterized by its dependence on
      de novo RNA and protein synthesis and morphological features of apoptosis. We
      confirmed that stimulated 2B4.11 (a murine T-cell hybridoma) and interleukin-3
      (IL-3)-deprived LyD9 (a murine haematopoietic progenitor cell line) died by the
      classical type of programmed cell death. Assuming that common biochemical
      pathways might be involved in the deaths of 2B4.11 and LyD9, we isolated the PD-1
      gene, a novel member of the immunoglobulin gene superfamily, by using subtractive
      hybridization technique. The predicted PD-1 protein has a variant form of the
      consensus sequence found in cytoplasmic tails of signal transducing polypeptides
      associated with immune recognition receptors. The PD-1 gene was activated in both
      stimulated 2B4.11 and IL-3-deprived LyD9 cells, but not in other death-induced
      cell lines that did not show the characteristic features of the classical
      programmed cell death. Expression of the PD-1 mRNA in mouse was restricted to the
      thymus and increased when thymocyte death was augmented by in vivo injection of
      anti-CD3 antibody. These results suggest that activation of the PD-1 gene may be
      involved in the classical type of programmed cell death.

PMID- 1396584
TI  - Receptor antagonist and selective agonist derivatives of mouse interleukin-2.
AB  - Mouse interleukin-2 (mIL-2) proteins with substitutions at two residues (D34 and
      Q141) that interact specifically with different signalling subunits
      (respectively, beta and gamma) of the IL-2 receptor (IL-2R) were examined using
      several in vitro cellular assays. Proteins with specific substitutions at both
      residues were partial agonists and their maximal responses varied widely in
      different IL-2-responsive cell types. Two of these cell types had comparable
      numbers of IL-2R and similar affinities for wild-type mIL-2 and mutant mIL-2
      proteins. However, the more responsive cell type had 'spare' IL-2R. Various mIL-2
      proteins with substitutions at Q141 had modest defects in IL-2R-binding and were
      potent antagonists of native mIL-2 action. Proteins with bulky or basic
      substitutions at residue D34 were weak antagonists due to severely reduced IL-2
      binding and their reduced binding paralleled their defects in IL-2R activation.
      Our results suggest that interaction of mIL-2 with IL-2R beta is more important
      for binding than activation and that the converse holds for mIL-2 interaction
      with IL-2R gamma. Also genetic manipulation of the interaction of IL-2 with IL-2R
      beta and IL-2R gamma has led to the discovery of potentially useful IL-2
      antagonists and selective agonists.

PMID- 1396583
TI  - A new gene, BCM, on chromosome 16 is fused to the interleukin 2 gene by a
      t(4;16)(q26;p13) translocation in a malignant T cell lymphoma.
AB  - A t(4;16)(q26;p13.1) chromosome translocation found in tumour cells from a
      patient with a T cell lymphoma was shown to rearrange the interleukin 2 gene,
      normally located on chromosome band 4q26, with sequences from chromosome band
      16p13.1. A cDNA library of tumour cells was screened with an interleukin 2 gene
      specific probe. Three clones were isolated, which consisted, from 5' to 3', of
      the three first exons of the interleukin 2 gene followed by a 16p13 in-frame
      sequence encoding 181 amino acids. A probe derived from this sequence detected a
      1.2 kb transcript in various cell lines exhibiting mature B lymphoid cell
      features, but this was not detected in other cell lines representative of other
      haematopoietic lineages, or in other organs. For this reason, the novel gene was
      termed BCM for B cell maturation. The open reading frame of BCM normal cDNA
      predicted a 184 amino acid protein with a single transmembrane domain which had
      no homology with any protein sequence stored in data banks. Our data indicate
      that BCM is a new gene whose expression coincides with B cell terminal
      maturation.

PMID- 1396586
TI  - Crystal structure of human platelet-derived growth factor BB.
AB  - The crystal structure of the homodimeric BB isoform of human recombinant platelet
      derived growth factor (PDGF-BB) has been determined by X-ray analysis to 3.0 A
      resolution. The polypeptide chain is folded into two highly twisted antiparallel
      pairs of beta-strands and contains an unusual knotted arrangement of three
      intramolecular disulfide bonds. Dimerization leads to the clustering of three
      surface loops at each end of the elongated dimer, which most probably form the
      receptor recognition sites.

PMID- 1396585
TI  - Identification of two C-terminal autophosphorylation sites in the PDGF beta
      receptor: involvement in the interaction with phospholipase C-gamma.
AB  - Two novel sites of autophosphorylation were localized to the C-terminal tail of
      the PDGF beta-receptor. To evaluate the importance of these phosphorylation
      sites, receptor mutants in which Tyr1009, Tyr1021 or both were replaced with
      phenylalanine residues, were expressed in porcine aortic endothelial (PAE) cells.
      These mutants were similar to the wild type receptor with regard to protein
      tyrosine kinase activity and ability to induce mitogenicity in response to PDGF
      BB. However, both the Y1009F and Y1021F mutants showed a decreased ability to
      mediate association with and the tyrosine phosphorylation of phospholipase C
      gamma (PLC-gamma) compared to the wild type PDGF beta-receptor; in the case of
      the Y1009F/Y1021F double mutant, no association or phosphorylation of PLC-gamma
      could be detected. These data show that tyrosine phosphorylation of PLC-gamma is
      dependent on autophosphorylation of the PDGF beta-receptor at Tyr1009 and
      Tyr1021.

PMID- 1396587
TI  - Oncogenic v-Abl tyrosine kinase can inhibit or stimulate growth, depending on the
      cell context.
AB  - The v-abl oncogene of Abelson murine leukemia virus (A-MuLV) induces two opposite
      phenotypes in NIH3T3 cells. In the majority of cells, v-abl causes a growth
      arrest at the G1 phase of the cell cycle; while in a minority of cells, v-abl
      abrogates the requirement for growth factors. Using temperature sensitive
      mutants, it can be demonstrated that v-Abl tyrosine kinase is required for growth
      inhibition or stimulation. The two phenotypes are not caused by mutations or
      differences in the expression of v-Abl, but are dependent on the cell context.
      Two stable subclones of NIH3T3 cells have been isolated that exhibit similar
      morphology and growth characteristics. However, upon infection with A-MuLV, the
      'positive' cells become serum- and anchorage-independent, whereas the 'negative'
      cells become arrested in G1. The positive phenotype is dominant, shown by cell
      fusion, and treatment with 5-azacytidine converts the negative cells to the
      positive phenotype. Activation of v-Abl tyrosine kinase induces the serum
      responsive genes in the positive but not in the negative cells. Transactivation
      of the c-fos promoter by v-Abl in transient assays is also restricted to the
      positive cells. These results show that v-Abl tyrosine kinase is not an
      obligatory activator of growth, but requires a permissive cellular context to
      manifest its mitogenic function.

PMID- 1396588
TI  - Microtubule bundling by tau proteins in vivo: analysis of functional domains.
AB  - Tau varies both in the N-terminal region (three types) and in the C-terminal
      repeated microtubule binding domain (two types), generating six isoforms through
      alternative splicing. To understand the differences between the isoforms and to
      determine which domains are important for microtubule bundling, we performed
      transfection studies on fibroblasts using tau isoforms and deletion mutants to
      quantify their ability to bundle microtubules. By comparing the isoforms, we
      found that a longer N-terminal region induced microtubule bundling more
      efficiently, but changes in the microtubule binding domain did not. Mutants
      lacking the proline rich region or the repeated domain did not bind to
      microtubules. Although all the other mutants could bind to and bundle
      microtubules, deletion in the N-terminal neutral region or the first half of the
      C-terminal tail caused a significant decrease in microtubule bundling, indicating
      the importance of these regions in microtubule bundling.

PMID- 1396589
TI  - Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
AB  - We have examined the role of phosphorylation in the regulation of human cyclin
      dependent kinase-2 (CDK2), a protein closely related to the cell cycle regulatory
      kinase CDC2. We find that CDK2 from HeLa cells contains three major tryptic
      phosphopeptides. Analysis of site-directed mutant proteins, expressed by
      transient transfection of COS cells, demonstrates that the two major
      phosphorylation sites are Tyr15 (Y15) and Thr160 (T160). Additional
      phosphorylation probably occurs on Thr14 (T14). Replacement of T160 with alanine
      abolishes the kinase activity of CDK2, indicating that phosphorylation at this
      site (as in CDC2) is required for kinase activity. Mutation of Y15 and T14
      stimulates kinase activity, demonstrating that phosphorylation at these sites (as
      in CDC2) is inhibitory. Similarly, CDK2 is activated in vitro by
      dephosphorylation of Y15 and T14 by the phosphatase CDC25. Analysis of HeLa cells
      synchronized at various cell cycle stages indicates that CDK2 phosphorylation on
      T160 increases during S phase and G2, when CDK2 is most active. Phosphorylation
      on the inhibitory sites T14 and Y15 is also maximal during S phase and G2. Thus,
      the activity of a subpopulation of CDK2 molecules is inhibited at a time in the
      cell cycle when overall CDK2 activity is increased.

PMID- 1396590
TI  - Isolation of multiple mouse cDNAs with coding homology to Saccharomyces
      cerevisiae CDC25: identification of a region related to Bcr, Vav, Dbl and CDC24.
AB  - In Saccharomyces cerevisiae, the product of the CDC25 gene is an essential Ras
      activator that appears to function by stimulating guanine nucleotide exchange on
      Ras. Using the ability of a mouse cDNA expression library to complement yeast
      cells lacking functional CDC25, Martegani et al. have identified a 1.7 kb partial
      cDNA from a gene, designated CDC25Mm, with homology to CDC25. We have now
      screened a mouse brain cDNA library to identify full-length clones of CDC25Mm.
      This cloning has led to the isolation of six distinct full-length cDNAs, each of
      which appear to be derived from the CDC25Mm gene, since their 3' 2 kb appear to
      be identical and to encode the same 661 C-terminal amino acids. Three cDNAs are
      predicted to encode protein products of 666 or 667 amino acids. The other three
      cDNAs encode products that are 836, 1120 and 1260 amino acids, respectively. A
      241 amino acid region near the N-terminus of the two largest products was found
      to have homology to a domain shared by Bcr, Vav, Dbl and CDC24. Polyclonal
      antibodies raised to a peptide encoded by all the cDNAs have identified at least
      two protein products in NIH3T3 fibroblasts. Their apparent molecular weights are
      75 and 95 kDa, which correspond closely to those predicted to be encoded,
      respectively, by the two shorter classes of cDNAs. In NIH3T3, the 95 kDa form is
      much more abundant than the 75 kDa form, while PC-12 pheochromocytoma cells
      contain relatively high levels of the 75 kDa form. We conclude that CDC25Mm is a
      complex gene whose protein products are regulated in a tissue-specific manner.

PMID- 1396591
TI  - The Saccharomyces cerevisiae NPS1 gene, a novel CDC gene which encodes a 160 kDa
      nuclear protein involved in G2 phase control.
AB  - We have cloned the gene NPS1 (nuclear protein of Saccharomyces) which encodes a
      nuclear protein of mol. wt 156 735 Daltons (1359 amino acids) essential for cell
      growth. NPS1 contains a 2 kb sequence that is highly homologous to the S.
      cerevisiae SNF2/GAM1 gene known as a transcriptional regulator for multiple
      genes. However, the NPS1 gene was found to have a distinct function from
      SNF2/GAM1. The growth of the cells carrying a nps1 delta :: URA3 deletion allele
      and galactose-inducible NPS1 on a plasmid was arrested under NPS1-repressed
      conditions with a cell cycle arrest phenotype, being arrested at the large-bud
      stage with a single nucleus that had a DNA content of G2/M phase. When the
      arrested cells were further incubated under NPS1-repressed conditions, re
      replication of DNA occurred in some of the arrested cells without passage through
      mitosis. In the predicted amino acid sequence of NPS1, sequences homologous to
      the catalytic domain of protein kinases were found. We constructed a mutation
      which results in the substitution of a highly conserved lysine residue (Lys792)
      in the presumed ATP-binding site of this kinase-like domain with a glutamic acid
      codon. The mutant gene failed to rescue the growth defect caused by NPS1
      disruption, suggesting that Lys792 is essential for the function of NPS1.

PMID- 1396593
TI  - Erythroid-specific activity of the glycophorin B promoter requires GATA-1
      mediated displacement of a repressor.
AB  - We have performed a detailed analysis of the cis-acting sequences involved in the
      erythroid-specific expression of the human glycophorin B (GPB) promoter and found
      that this promoter could be divided into two regions. The proximal region, -1 to 
      60, contains a GATA binding sequence around -37 and an SP1 binding sequence
      around -50. This region is active in erythroid and non-erythroid cells. The
      distal region, -60 to -95, contains two overlapping protein binding sites around 
      75, one for hGATA-1 and one for ubiquitous proteins. This distal region
      completely represses the activity of the proximal promoter in non-erythroid cells
      and defines the -95 GPB construct as a GPB promoter that displays erythroid
      specificity. Using site directed mutagenesis, we show that the -37 GATA and the 
      50 SP1 binding sites are necessary for efficient activity of the -95 GPB
      construct. Mutations that impair the -75 GATA-1 binding result in extinction of
      the -95 GPB construct activity if the -75 ubiquitous binding site is not altered,
      or in loss of erythroid specificity if the -75 ubiquitous binding site is also
      mutated. Using a cotransfection assay, we found that hGATA-1 can efficiently
      activate transcription of the -95 GPB construct in non-erythroid cells. This
      transactivation is abolished by mutations that impair either the -37 GATA-1 or
      the -50 SP1 binding. Mutations that impair the -75 GATA-1 binding and still allow
      the -75 ubiquitous binding also abolish the transactivation of the -95 GPB
      construct, indicating that hGATA-1 can remove repression of the GPB promoter by
      displacement of the ubiquitous proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396592
TI  - The SCL gene product: a positive regulator of erythroid differentiation.
AB  - The SCL (tal-1, TCL5) gene is a member of the basic domain, helix-loop-helix
      (bHLH) class of putative transcription factors. We found that (i) the SCL
      promoter for exon Ia contains a potential recognition site for GATA-binding
      transcription factors, (ii) SCL mRNA is expressed in all erythroid tissues and
      cell lines examined, and (iii) SCL mRNA increases upon induced differentiation of
      murine erythroleukemia (MEL) cells, and inferred that SCL may play a physiologic
      role in erythroid differentiation. We used gel shift and transfection assays to
      demonstrate that the GATA motif in the SCL promoter binds GATA-1 (and GATA-2),
      and also mediates transcriptional transactivation. To identify a role for SCL in
      erythroid differentiation, we generated stable transfectants of MEL and K562 (a
      human chronic myelogenous leukemia cell line that can differentiate along the
      erythroid pathway) cells overexpressing wild-type, antisense or mutant SCL cDNA.
      Increasing the level of SCL expression in two independent MEL lines (F4-6 and
      C19, a 745 derivative) and K562 cells increased the rate of spontaneous (i.e. in
      the absence of inducer) erythroid differentiation. Conversely, induced
      differentiation was inhibited in MEL transfectants expressing either antisense
      SCL cDNA or a mutant SCL lacking the basic domain. Our experiments suggest that
      the SCL gene can be a target for the erythroid transcription factor GATA-1 and
      that the SCL gene product serves as a positive regulator of erythroid
      differentiation.

PMID- 1396594
TI  - GT-2: a transcription factor with twin autonomous DNA-binding domains of closely
      related but different target sequence specificity.
AB  - A triplet of adjacent, highly similar GT motifs in the phyA promoter of rice
      functions to support maximal expression of this gene. We have obtained a
      recombinant clone that encodes a full-length nuclear protein, designated GT-2,
      which binds specifically to these target sequences. This novel protein contains
      acidic, basic and proline- + glutamine-rich regions, as well as two autonomous
      DNA-binding domains, one NH2-terminal and the other COOH-terminal, that
      discriminate with high resolution between the three GT motifs. A duplicated
      sequence of 75 amino acids, present once in each DNA-binding domain, appears
      likely to mediate DNA target element recognition. Each copy of this duplicated
      protein sequence is predicted to form three amphipathic alpha-helices separated
      from each other by two short loops. The absence of sequence similarity to other
      known proteins suggests that this predicted structural unit, which we term the
      trihelix motif, might be representative of a new class of DNA-binding proteins.

PMID- 1396595
TI  - Two distinct yeast transcriptional activators require the function of the GCN5
      protein to promote normal levels of transcription.
AB  - When yeast cells are grown under conditions of amino acid limitation,
      transcription of amino acid biosynthetic genes is increased through the action of
      the GCN4 transcriptional regulator. gcn5 mutant strains exhibit poor growth under
      such conditions. We have established that GCN4 requires the function of GCN5 in
      order to promote normal levels of transcriptional activation. In addition, we
      have shown that GCN5 is also required for the activity of the HAP2--HAP3--HAP4
      transcriptional activation complex, which mediates the transcription of genes
      involved in respiratory functions. Thus, GCN5 is a new member of the recently
      revealed general class of transcriptional regulators that collaborate with
      certain specific DNA binding activators to promote high levels of transcription.
      We have cloned and sequenced the GCN5 gene. The deduced GCN5 protein contains a
      region conserved in other yeast, Drosophila and human proteins, all members of
      this new class of transcriptional activators.

PMID- 1396596
TI  - mRNAs containing extensive secondary structure in their 5' non-coding region
      translate efficiently in cells overexpressing initiation factor eIF-4E.
AB  - Cellular eukaryotic mRNAs (except organellar) contain at the 5' terminus the
      structure m7(5')Gppp(5')N (where N is any nucleotide), termed cap. Cap
      recognition by eukaryotic initiation factor eIF-4F plays an important role in
      regulating the overall rate of translation. eIF-4F is believed to mediate the
      melting of mRNA 5' end secondary structure and facilitate 43S ribosome binding to
      capped mRNAs. eIF-4E, the cap-binding subunit of eIF-4F, plays an important role
      in cell growth; its overexpression results in malignant transformation of rodent
      cells, and its phosphorylation is implicated in signal transduction pathways of
      mitogens and growth factors. The molecular mechanism by which eIF-4E transforms
      cells is not known. Here, we report that overexpression of eIF-4E facilitates the
      translation of mRNAs containing excessive secondary structure in their 5' non
      coding region. This effect may represent one mechanism by which eIF-4E regulates
      cell growth and transforms cells in culture.

PMID- 1396598
TI  - The leaky UGA termination codon of tobacco rattle virus RNA is suppressed by
      tobacco chloroplast and cytoplasmic tRNAs(Trp) with CmCA anticodon.
AB  - RNA-1 molecules from tobacco rattle virus (TRV) and pea early-browning virus
      (PEBV), two members of the tobravirus group, have recently been shown to contain
      internal, in-frame UGA termination codons which are suppressed in vitro. Our
      results suggest that a UGA stop codon also exists in RNA-1 of pepper ringspot
      virus (PRV), another tobravirus. UGA suppression may therefore be a universal
      feature of the expression of tobravirus genomes. We have isolated two natural
      suppressor tRNAs from uninfected tobacco plants on the basis of their ability to
      promote readthrough over the leaky UGA codon of TRV RNA-1 in a wheat germ extract
      depleted of endogenous mRNAs and tRNAs. Their amino acid acceptance and
      nucleotide sequences identify the two UGA-suppressor tRNAs as chloroplast (chl)
      and cytoplasmic (cyt) tryptophan-specific tRNAs with the anticodon CmCA. These
      are the first UGA suppressor tRNAs to be identified in plants. They have several
      interesting features. (i) Chl tRNA(Trp) suppresses the UGA stop codon more
      efficiently than cyt tRNA(Trp). (ii) Chl tRNA(Trp) contains an A24:U11 pair in
      the D-stem as does the mutated Escherichia coli UGA-suppressor tRNA(Trp) which is
      a more active suppressor than wild-type tRNA(Trp). (iii) The suppressor activity
      of chl tRNA(Trp) is dependent on the nucleotides surrounding the stop codon
      because it recognizes UGA in the TRV context but not the UGA in the beta-globin
      context.

PMID- 1396597
TI  - Recognition of bases in Escherichia coli tRNA(Gln) by glutaminyl-tRNA synthetase:
      a complete identity set.
AB  - The fidelity of protein biosynthesis rests largely on the correct aminoacylation
      of transfer RNAs by their cognate aminoacyl-tRNA synthetases. Previous studies
      have demonstrated that the interaction of Escherichia coli tRNA(Gln) with
      glutaminyl-tRNA synthetase (GlnRS) provides an excellent system for studying the
      basis of this highly specific recognition process. Correct aminoacylation depends
      on the set of nucleotides (identity elements) in tRNA(Gln) responsible for
      correct interaction with GlnRS. Specific contacts between tRNA(Gln) and GlnRS
      include the 2-amino group of guanosines. Therefore, we made a set of tRNA(Gln)
      variants in which specific guanosines were replaced by inosine using recombinant
      RNA technology. This resulted in a set of tRNAs that varied by single deletions
      of the amino group from guanine residues, thus allowing us to test the functional
      importance of these contacts. In addition, a number of mutants were made by
      transcription of mutated tRNA genes with base changes at position 10, 16 or 25.
      In vitro aminoacylation of these mutants showed decreases in the specificity
      constant (kcat/KM) of up to 300-fold, with kcat being the parameter most
      affected. These experiments reveal G10 as a new element of glutamine identity. In
      addition, the interaction of G2, G3 and G10 with GlnRS via the 2-amino group is
      significant for tRNA discrimination. Based on these results, and on earlier data,
      we propose a complete set of bases as identity elements for tRNA(Gln).

PMID- 1396599
TI  - Comparison of the expression of the seven ribosomal RNA operons in Escherichia
      coli.
AB  - We have compared the expression of the seven ribosomal RNA operons (rrn) of
      Escherichia coli and their responses to a variety of physiological and genetic
      perturbations. We used a set of rrn promoter fusion constructs in their native
      chromosomal positions to examine effects of chromosomal location on rrn operon
      expression and the same set of fusions on lambda lysogens to assay intrinsic
      promoter strengths independent of chromosome context. In its native chromosomal
      location, expression of the rrnH operon was significantly lower than expected.
      This effect was not attributable to weak promoter activity and was dependent on
      the growth medium. The rrnE operon had reduced promoter activity relative to the
      other ribosomal operons in minimal medium and thus appears to have abnormal
      growth rate regulation. The ribosomal RNA operons showed varied responses to
      amino acid starvation; expression of rrnD was inhibited most. There was only a
      slight increase in rrn transcription in response to a temperature shift (30
      degrees C to 42 degrees C) and the differences between individual operons was
      very small. The rrnG operon showed a significantly lower response than the other
      ribosomal RNA operons to a depletion of the rrn transcription activator, Fis, and
      thus appears to have decreased Fis-mediated transactivation. Finally, the
      chromosomal fusion strains were used to study the effect on growth rate of
      inactivating each rrn operon. In fast growth conditions, loss of certain rrn
      operons caused subtle decreases in growth rate on complex medium.

PMID- 1396600
TI  - The carboxy-terminal 10 amino acid residues of cytochrome b5 are necessary for
      its targeting to the endoplasmic reticulum.
AB  - Cytochrome b5 is an integral membrane protein located on the outer surface of the
      endoplasmic reticulum (ER). This cytochrome is considered to be synthesized on
      free ribosomes and to be inserted post-translationally into the ER membrane,
      without participation of a signal recognition particle. To elucidate the signal
      responsible for targeting of cytochrome b5 to the ER membrane in vivo, DNAs
      encoding various derivatives of the cytochrome were constructed and introduced
      into cultured mammalian COS cells, and the subcellular distributions of the
      derivatives expressed in the cells were then analyzed. The deletion of more than
      11 amino acid residues at the carboxy-terminal end of cytochrome b5 abolished the
      targeting and anchoring of the cytochrome to the ER membrane. Fusion proteins
      consisting of the carboxy-terminal 10 amino acid residues of cytochrome b5 and
      passenger proteins with the hydrophobic portion could be localized in the ER
      membrane. Thus, the last 10 amino acid residues of cytochrome b5 carry
      information necessary for the cytochrome to be targeted to the ER membrane.

PMID- 1396601
TI  - Fission yeast and a plant have functional homologues of the Sar1 and Sec12
      proteins involved in ER to Golgi traffic in budding yeast.
AB  - Sec12p and Sar1p are required for the formation of transport vesicles generated
      from the endoplasmic reticulum (ER) in the yeast Saccharomyces cerevisiae. Sec12p
      is an ER type II membrane protein that mediates the membrane attachment of the
      GTP-binding Sar1 protein. The SAR1 gene is a multi-copy suppressor of a
      thermosensitive sec12 mutation. In an attempt to identify functional homologues
      of Sec12p and Sar1p from other eukaryotic organisms, we screened cDNA expression
      libraries derived from the fission yeast Schizosaccharomyces pombe and from the
      plant Arabidopsis thaliana for complementation of the sec12ts mutation. Four
      individual cDNAs were isolated, two of which encode the S. pombe and A. thaliana
      homologues of Sar1p. The three Sar1 proteins are 67% identical on average. The
      two other cDNAs encode type II membrane proteins which were designated Stl1p for
      the S. pombe protein and Stl2p for the A. thaliana protein (Stl stands for Sec12p
      like). Both proteins have NH2-terminal cytoplasmic domains which resemble that of
      Sec12p: they are similar in size and present a significant degree of amino acid
      identity with the cytoplasmic domain of Sec12p. In contrast, the lumenal domains
      of Sec12p, Stl1p and Stl2p are very different in size and do not show any
      appreciable homology. That Stl1p and Stl2p are functional homologues of Sec12p
      was confirmed by showing that expression of either cloned gene complements a
      sec12 null mutation. Our results indicate that some of the mechanisms regulating
      vesicle formation at the ER are conserved not only in yeasts, but also in plants.

PMID- 1396602
TI  - DNA damage-inducible origins of DNA replication in Escherichia coli.
AB  - Upon induction of the SOS response in Escherichia coli, the mode of initiation of
      DNA replication is altered such that it can occur in the absence of normally
      required protein synthesis. This type of DNA replication has been termed induced
      stable DNA replication (iSDR). We examined the origin usage during iSDR and found
      that the initiation of iSDR occurs primarily in the oriC and terC regions of the
      chromosome in a manner completely independent of transcription, translation and
      DnaA protein. Minichromosomes (oriC plasmids) pOC23 and pOC81 were induced to
      replicate in the absence of DnaA protein and transcription after SOS induction.
      The results localized one of the iSDR origin activities in a 596 bp region which
      includes the minimal oriC.

PMID- 1396604
TI  - Transgenic mouse mutation assays: potential for confusion of genotoxic and non
      genotoxic carcinogenesis: a proposed solution.

PMID- 1396603
TI  - Site-directed mutagenesis at the Exo III motif of phi 29 DNA polymerase;
      overlapping structural domains for the 3'-5' exonuclease and strand-displacement
      activities.
AB  - In this report we present the alignment of one of the most conserved segments
      (Exo III) of the 3'-5' exonuclease domain in 39 DNA polymerase sequences,
      including prokaryotic and eukaryotic enzymes. Site-directed substitutions of the
      two most conserved residues, which form the Exo III motif Tyr-(X)3-Asp of phi 29
      DNA polymerase, did not affect single-stranded DNA binding, DNA polymerization,
      processivity or protein-primed initiation. In contrast, substitution of the
      highly conserved Tyr residue by Phe or Cys decreased the 3'-5' exonuclease
      activity to 7.5 and 4.1%, respectively, of the wild-type activity. Change of the
      highly conserved Asp residue into Ala resulted in almost complete inactivation
      (0.1%) of the 3'-5' exonuclease. In accordance with the contribution of the 3'-5'
      exonuclease to the fidelity of DNA replication, the three mutations in the Exo
      III motif (Y165F, Y165C and D169A) produced enzymes with an increased frequency
      of misinsertion and extension of DNA polymerization errors. Surprisingly, the
      three mutations in the Exo III motif strongly decreased (80- to 220-fold) the
      ability to replicate phi 29 DNA, this behaviour being due to a defect in the
      strand displacement activity, an intrinsic property of phi 29 DNA polymerase
      required for this process. Taking these results into account, we propose that the
      strand displacement activity of phi 29 DNA polymerase resides in the N-terminal
      domain, probably overlapping with the 3'-5' exonuclease active site.

PMID- 1396605
TI  - Tissue-specific genotoxic effects of acrylamide and acrylonitrile.
AB  - Acrylamide (AA) has been reported to induce dominant lethal mutations in male rat
      germ cells and tumors in a variety of organs, including the scrotum, thyroid and
      mammary glands, but not the liver of rats. The structurally similar vinyl monomer
      acrylonitrile (ACN) does not induce dominant lethal mutations but does induce
      tumors of the brain, Zymbal gland, forestomach and mammary gland, but not the
      liver of rats. Several in vitro and/or in vivo unscheduled DNA synthesis (UDS)
      assays were employed to examine the potential tissue-specific genotoxic activity
      of these compounds. Neither AA nor ACN induced DNA repair in either the in vitro
      or in vivo hepatocyte DNA repair assays. Glycidamide (GA), a mutagenic metabolite
      of AA, induced DNA repair in the in vitro hepatocyte DNA repair assay.
      Cyanoethylene oxide (CEO), a mutagenic metabolite of ACN, did not yield a DNA
      repair response in the in vitro hepatocyte DNA repair assay, but was highly toxic
      and could not be tested at doses equivalent to GA. AA, but not ACN, produced a
      DNA repair response in the in vivo spermatocyte DNA repair assay. AA produced a
      slight response in the in vitro human mammary epithelial cell (HMEC) DNA repair
      assay in normal cells derived from discarded surgical samples from five different
      women. GA produced a strong UDS response in all cases in the same assay. CEO, but
      not its parent compound ACN, produced a response in the HMEC DNA repair assay.
      These results show a highly tissue-specific pattern of genotoxic activity for AA
      and ACN that correlates, to the extent that it has been examined, with the tissue
      specific pattern of carcinogenic and dominant lethal activity. The induction of
      DNA repair by GA and CEO confirms the genotoxic potential of these metabolites.
      While the observation of genotoxic activity of AA in the HMEC DNA repair assay
      suggests that mammary cells might be a target for carcinogenic activity of this
      compound in humans, other factors such as pharmacokinetics and epidemiology must
      be evaluated to establish that effect.

PMID- 1396606
TI  - Posttreatment with sodium arsenite alters the mutational spectrum induced by
      ultraviolet light irradiation in Chinese hamster ovary cells.
AB  - Arsenic, a potent carcinogen, fails to induce gene mutations in mammalian cells.
      However, posttreatment of ultraviolet light (UV) irradiated cells with sodium
      arsenite synergistically enhances the mutation frequency on the hypoxanthine
      (guanine) phosphoribosyltransferase locus. To investigate the molecular mechanism
      of the comutagenic effects of sodium arsenite, we characterized the alterations
      of nucleotide sequences in 30 UV-induced and 39 sodium arsenite enhanced hprt
      mutants from Chinese hamster ovary K1 cells by direct sequencing of mRNA-PCR
      amplified cDNA. The majority of sequence alterations derived from UV irradiation
      (80%) and from sodium arsenite posttreatment (70%) were single base
      substitutions. UV irradiation induced all types of base substitutions. Among
      them, 57% were transversions. The frequency of transversions increased to 70% in
      sodium arsenite enhanced mutants. While base substitutions observed in UV-induced
      mutants were evenly distributed along with the whole coding region, exons 3 and 8
      were most frequently mutated in sodium arsenite enhanced mutants. Sodium arsenite
      posttreatment did not alter the strand bias for mutation induction, i.e., 73% and
      78%, of the mutations were located on the non-transcribed strand in UV-induced
      and sodium arsenite enhanced mutants, respectively. In contrast to UV-induced
      mutations, bases at the 5' position of TT and the 3' position of CT sequences
      were the most frequent mutation sites observed in sodium arsenite enhanced
      mutants. We hypothesize that sodium arsenite may interfere with the process of
      mutation fixation of TT and CT dimers during DNA replication.

PMID- 1396607
TI  - Optimization of the concurrent assay for gene mutations and chromosomal
      aberrations in vivo: expression time in rats.
AB  - Ethylnitrosourea was used as a model mutagen to determine the time at which the
      most mutants and chromosomal aberrations could be detected. Primary fibroblasts
      derived from Fischer (F344) rats that had been mutagenized by ethylnitrosourea in
      vivo, were grown in culture and sampled at increasing intervals to analyze,
      quantitatively, gene mutations and chromosomal aberrations. Since
      ethylnitrosourea reacts very quickly and the cells were isolated five hours after
      treatment, expression time represents the intracellular processes involved, not
      the pharmacokinetics of the mutagen. A thioguanine selection procedure was used
      to quantify gene mutations. A cytochalasin B technique for micronuclei was used
      to quantify chromosomal aberrations. A significant increase in the number of
      mutations was observed on the ninth day in an experiment wherein sampling was
      done at increasing intervals of three days. One of two experiments wherein
      sampling was done at increasing intervals of five days showed maximum number of
      mutations in dishes plated with cells, exposed to maximum dose (200 mg/kg), on
      the tenth day for selection. Cells that received dose 100 mg/kg on the contrary
      produced maximum number of mutant colonies in dishes that were plated on the 20th
      day for selection. A repeat of the 5-day interval experiment showed maximum
      number of mutant colonies in dishes selected on the tenth day, irrespective of
      the dose used. The number of micronuclei reached a maximum on the third day.

PMID- 1396608
TI  - Chromosomal breakage following treatment of CHO-K1 cells in vitro with U-68,553B
      is due to induction of undercondensation of heterochromatin.
AB  - Preferential breakage of chromosomes at specific sites (so-called "fragile
      sites") has been observed to occur spontaneously, and has been induced by some
      metal salts and chemicals. Furthermore, a heterochromatic region of the long arm
      of the Chinese hamster ovary (CHO) X-chromosome is known to be susceptible to a
      disproportionately high frequency of spontaneous breakage; unless there is
      physical displacement of chromatin the resulting achromatic lesions are not
      scored as structural aberrations. We have encountered such anomalous breakage
      associated with C-band positive regions of the chromosomes of a CHO-K1 cell line
      following exposure of the cells to toxic doses of U-68,553B and in this report
      present evidence that the apparent breaks are due to undercondensed
      heterochromatin (UH) and evidence that the phenomenon appears to occur at higher
      frequency in a particular cell line of Chinese hamster. This finding has
      important implications on the assessment of potential risk due to exposure to the
      drug. Such apparent breaks at sites of UH in chromosome 1 was not observed in an
      alternate CHO cell line (CHO-WBL) which supports the notion that the UH
      associated achromatic lesions in the CHO-K1 line may be a cell line specific
      phenomenon. Furthermore, careful electron microscopy of the chromosomes revealed
      chromatin fibers connecting the apparently broken chromosomes. The UH was not
      observed in the presence of added metabolic activation (S9), and thus the
      significance of the phenomenon in risk assessment is further reduced. The data
      presented here provide evidence that sites of UH occur preferentially at
      locations of C-band positive constitutive heterochromatin in CHO cells; we
      believe that this is the first report of induced fragile sites in rodent cells in
      vitro documented in this way. In addition, evidence is presented that U-68,553B
      lacks the ability to induce breakage in vivo in rodents and lacks the ability to
      induce chromosome breakage in human peripheral lymphocytes in vitro. Therefore,
      it is concluded that the positive results with CHO-K1 cells treated with U
      68,553B are unlikely to be predictive of a genotoxic hazard. This is a specific
      example of the importance of careful followup to an in vitro result in risk
      assessment.

PMID- 1396609
TI  - Evaluation of the mutagenicity of an N-nitroso contaminant of the sunscreen
      Padimate O: N-nitroso-N-methyl-p-aminobenzoic acid, 2-ethylhexyl ester (NPABAO).
AB  - The nitrosamine contaminant, N-nitroso-N-methyl-p-aminobenzoic acid, 2-ethylhexyl
      ester (NPABAO), of the major sunscreen ingredient Padimate O (4-N,N'
      dimethylamino-benzoic acid, 2-ethylhexyl ester) was synthesized and tested for
      mutagenicity in the Salmonella typhimurium and mouse lymphoma L5178Y TK +/-
      assays. In contrast to the previously reported positive responses in S.
      typhimurium tester strains TA100 and TA1535 [Loeppky et al., 1991], there were no
      increases in the number of revertants with strains TA98, TA100, TA1535, and
      TA1538 in either the Salmonella plate incorporation [Ames et al., 1975] or
      preincubation [Yahagi et al., 1977] assays. Additional testing with Salmonella,
      following the modified preincubation procedure [Rogan, 1990] that gave the
      initial positive response, was also negative. Data from the mouse lymphoma assays
      were also uniformly negative. During synthesis of NPABAO, small amounts of 4-N,N'
      dimethylamino-3-nitrobenzoic acid, 2-ethylhexyl ester (DMANBAO) can be formed. To
      determine whether the reported positive mutagenicity response of NPABAO could be
      the result of trace amounts of DMANBAO in the NPABAO, that compound was also
      synthesized and tested for mutagenicity with Salmonella. Positive responses were
      obtained with tester strains TA98 and TA 1538 but not with TA100 and TA1535,
      indicating that DMANBAO was not responsible for the increase in revertants
      originally reported.

PMID- 1396610
TI  - Chlorophyllin-enhanced excretion of urinary and fecal mutagens in rats given 2
      amino-3-methylimidazo[4,5-f]quinoline.
AB  - Sodium/copper chlorophyllin (CHL) is a water-soluble derivative of chlorophyll
      that exhibits antimutagenic activity in several short-term genotoxicity assays
      and inhibits carcinogen-DNA binding in vivo. The effect of CHL pretreatment on
      the excretion of mutagens in the urine and feces of male Sprague-Dawley rats has
      been studied using the Salmonella mutagenicity assay. Animals were given 1
      percent CHL in the drinking water for 2 days before administering a single dose
      of 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) by oral gavage. Rats pretreated
      with CHL had higher levels of mutagens in the urine and feces compared with
      animals given IQ alone; 48 hr after IQ administration, the total mutagenic dose
      excreted was < 4% in controls vs. 18% in rats given CHL. Mutagenicity required
      the presence of an activation system, was unaffected by treatment with beta
      glucuronidase or arylsulfatase, and in both the urine and feces was accounted for
      by increased elimination of unmetabolized parent compound. The results support
      the view that CHL may operate in vivo as a "desmutagen" or interceptor molecule,
      interacting with IQ in the gut and tissues, and reducing carcinogen
      bioavailability.

PMID- 1396611
TI  - Beta-carotene as a modulator of chromosomal aberrations induced in mouse bone
      marrow cells.
AB  - The inhibitory effects of beta-carotene on cyclophosphamide (CPA)-induced
      chromosomal aberrations in mouse bone marrow cells were investigated. Male Balb C
      mice, 8-10 weeks old, were treated with beta-carotene (0.5, 1.0, 2.0, 5.0, 10,
      25, 50, 100, and 200 mg/kg) or with corn oil (0.05 ml/10 g b.w.) by gavage for 5
      consecutive days. Four hours after the last treatment with or without beta
      carotene, the animals were intraperitoneally injected with CPA and killed 24 hr
      later for cytological preparations and analysis. The results obtained show that
      beta-carotene provides significant protection against the clastogenicity of CPA.
      The maximum reduction in the frequency of aberrant metaphases (26.9%) and in
      total number of chromosomal aberrations were observed when beta-carotene was used
      at 50 mg/kg. Nevertheless, no direct dose-response relationship was detected,
      suggesting that beta-carotene might act through different mechanisms at different
      doses. The results obtained in animals studies have served as part of the basis
      for the human intervention studies now underway to determine if beta-carotene
      does indeed function as a chemopreventive agent in human nutrition.

PMID- 1396612
TI  - The role of glutathione in the bacterial mutagenicity of vapour phase
      dichloromethane.
AB  - Dichloromethane (DCM) vapour by inhalation is carcinogenic to rodents and is an
      in vivo rodent cell clastogen and a bacterial mutagen. It has been suggested that
      the bacterial mutagenicity of DCM is mediated by glutathione (GSH) conjugation.
      The involvement of endogenous and exogenous GSH in the conversion of DCM to a
      bacterial mutagen has been studied in a vapour phase protocol using wild-type and
      GSH-deficient (NG54; gsh) Salmonella typhimurium TA100 strains in the presence
      and absence of various rat liver fractions. The effect of the duration of
      exposure was also investigated in these Salmonella strains and in E. coli WP2
      uvrA pKM101. Dose- and time-related increases in revertants occurred with all
      metabolic activation systems used (without exogenous metabolic activation; with
      Aroclor-induced rat liver S9, microsomes, or cytosol fractions), with minor
      quantitative differences among the 3 strains. Mutagenicity was marginally highest
      in the presence of cytosol at the highest DCM concentrations. Strain NG54 gsh,
      which contains approximately 25% of the TA100 level of GSH/microgram protein, was
      slightly less responsive to DCM-induced mutagenicity than TA100. Addition of 0.33
      mumoles/plate of GSH had little effect on the mutagenic responses of TA100 or
      NG54 in the presence or absence of S9. In these 2 strains, exogenous S9 produced
      small increases in mutagenicity at the highest concentrations of DCM (2 and 4%
      v/v). These results suggest that if an interaction between DCM and GSH is
      required for the activation of DCM to a bacterial mutagen, it occurs at low
      levels of endogenous GSH and is not significantly affected by GSH
      supplementation.

PMID- 1396613
TI  - Effect of permethrin on the induction of sister chromatid exchanges and
      micronuclei in cultured human lymphocytes.

PMID- 1396614
TI  - Hookworm infection among the Melka Sedi banana plantation residents, middle Awash
      Valley, Ethiopia.
AB  - A study of intestinal parasites was done among the people who lived within the
      banana plantation zone of the Melka Sedi Agricultural Enterprise, Awash Valley,
      Ethiopia in April 1987. The methods of parasite detection were the Ritchie formal
      ether and the charcoal culture method for hookworm larvae species identification.
      From the total 633 population, 311 were examined at random of whom 60.8% were
      positive for one or more intestinal parasites. Eight parasites were encountered,
      Ascaris lumbricoides in 1.3%, Trichuris trichiura in 6.4%, Strongyloides
      stercoralis in 3.9%, hookworm in 53.1%, Taenia sp. in 3.5%, Schistosoma mansoni
      in 1.9%, Entamoeba histolytica in 0.6% and Hymenolepis sp. in 0.6%. Prevalence of
      hookworm infection was significantly higher than that of any of the other
      parasites (p less than 0.001). In the hookworm infected individuals there were
      more males than females, and the 25 to 34 year age group had significantly higher
      infection rates (p less than 0.05). The majority of those with hookworm were
      banana plantation workers. This communication emphasizes the basic guidelines for
      control and prevention of hookworm and other related faecal/soil-borne infections
      in this and similar agricultural settings.

PMID- 1396615
TI  - Epidemic meningococcal meningitis in adult Ethiopians in Addis Abeba, Ethiopia,
      1988.
AB  - 278 patients with pyogenic meningitis admitted to the Tikur Anbessa Teaching
      Hospital in Addis Abeba, Ethiopia, between January and December 1988 were studied
      prospectively to describe the epidemiology, microbiology, clinical features and
      outcome of infection. Fifty-nine per cent of the patients were admitted in the
      hot dry season between January and the end of June. About half of the patients
      (57%) were in the age group 15 to 19 years; the male to female ratio was 1.8:1.
      Two hundred sixty-two specimens (94%) were examined by Gram stain/or culture. N.
      Meningitidis was cultured from 161 of 243 CSF specimens (65%) and the Gram stain
      was diagnostic in 108 of 140 CSF specimens (77%). Both Gram stain and culture
      were negative in 90 of 262 specimens (34%). Thirty-five of the isolates were sero
      grouped and all were found to belong to serogroup A. All 30 isolates tested for
      drug sensitivity were resistant to sulfadiazine but sensitive to penicillin.
      Forty-three of 204 patients died of their infection, a case fatality rate of 21%:
      60% of the deaths occurred in the first 24 hours after admission. Eleven of 13
      patients with meningococcaemia expired. The case fatality rates for meningitis
      and meningococcaemia were 16% and 85% respectively. Nine patients (4%) developed
      neurologic sequelae: 4 hemiplegia, 3 nerve deafness, 2 cranial nerve palsies.
      This high morbidity and mortality from meningococcal infection demonstrates the
      need for a national surveillance programme for the prevention and control of
      meningococcal disease in the country.

PMID- 1396616
TI  - Multiple myeloma in Ethiopians: analysis of 22 cases.
AB  - Twenty-two cases of multiple myeloma were seen in the Department of Internal
      Medicine, Tikur Anbessa (Black Lion) Hospital, a teaching and referral hospital
      in Addis Abeba, Ethiopia, from January 1983 to December 1990. The age range was
      38 to 76 (mean +/- SD = 51.5 +/- 12.2) years; a third were in the fifth decade.
      The male:female ratio was 1.75:1. The common clinical findings were bone pain in
      20 (91%), bone tenderness in 15 (68%), anaemia in 14 (64%) and spinal cord
      compression in 8 (36%). The erythrocyte sedimentation rate (ESR) was raised in
      21. Serum protein was raised in 17 (77%) and hyperglobulinaemia was seen in 20
      (91%). Serum uric acid, blood urea nitrogen (BUN) and calcium were elevated in
      10, 8 and 5 patients respectively, Bence-Jones proteinuria and albuminuria were
      each found in 9 patients. All patients had radiological abnormalities; 9 had a
      combination of lytic lesions, osteoporosis and pathological fractures (41%). Ten
      patients presented in clinical stage III. Four patients are being followed after
      3-84 (median 40.5) months; eight were lost to follow-up 1-8 (median 2.0) months
      after diagnosis. Ten patients have died after 1-55 (median 11) months. Multiple
      myeloma is not uncommon in Ethiopians. Except for a lower age at presentation,
      the clinical, haematological, biochemical, and radiological findings, and the
      response to therapy, are similar to those reported elsewhere.

PMID- 1396617
TI  - Attitude of medical students to future practice characteristics.
AB  - In November 1990, 14.5% of the 271 medical students of the Gonder College of
      Medical Science (G.C.M.S.), Gonder, Ethiopia, were of peasant background. Only
      10.2% of the 271 expressed willingness to serve for more than two years in the
      rural areas after graduation, and, of those not willing, a higher proportion
      (15.5%) were from the main towns than from rural areas (1.2%). Specialty choice
      of senior students showed obstetrics-gynaecology, other specialties such as
      dermatology, internal medicine and surgery as the most preferred career goals. In
      addition, 67.2% of the students agreed that there is a greater need for
      physicians in rural than urban settings, agreement being six times more frequent
      by Clinical Year I students than interns (referent group). Among twelve personal
      and professional variables suggested, continuing education, schools for children,
      and private practice were considered better in urban than in rural areas. The
      study has important implications for medical education.

PMID- 1396618
TI  - Childhood malignancies in an Ethiopian teaching hospital.
AB  - A retrospective study for the ten year period 1981 to 1990 was done to determine
      the pattern of childhood malignant diseases in the Paediatrics Department of the
      Gonder College of Medical Sciences, Gonder, Ethiopia. The 71 children identified
      represented 0.66% of the total paediatric admissions. Ages ranged between 4
      months and 14 years with the male to female ratio 3.4:1. Lymphoma was the
      commonest tumour (25.4%) followed by bone and soft tissue sarcomas (19.7%) and
      retinoblastoma (15.5%). Leukaemia accounted for 11.3% of the cases. The findings
      are compared with those from other countries.

PMID- 1396619
TI  - The efficacy of hydrochlorothiazide, timolol and enalapril in Ethiopians with
      essential hypertension.
AB  - A double-blind trial of hydrochlorothiazide, timolol and enalapril was carried
      out in Ethiopians with essential hypertension at the Tikur Anbessa Hospital,
      Addis Abeba, between 1987 and 1990. Patients with a supine diastolic blood
      pleasure of 95-120 mmHg after a washout period of 2 weeks were randomized to
      receive hydrochlorothiazide 25 mg daily, timolol 10 mg daily or enalapril 10 mg
      daily. Doses were doubled at 4 weeks if the diastolic blood pressure remained
      above 95 mmHg. At the end of 8 weeks of treatment, there were 9 patients taking
      hydrochlorothiazide, 10 patients taking timolol and 7 patients taking enalapril.
      Hydrochlorothiazide significantly lowered both systolic and diastolic blood
      pressure at 4 and 8 weeks compared with pre-treatment levels. Timolol and
      enalapril did not significantly lower the systolic blood pressure, but each
      lowered the diastolic blood pressure at 4 weeks and 8 weeks respectively. More
      patients on hydrochlorothiazide attained a diastolic blood pressure of less than
      90 mmHg while less patients required doubling of dosage compared to timolol and
      enalapril. It is concluded that Ethiopian hypertensives may respond better to
      diuretics than to beta-blockers or angiotensin converting enzyme inhibitors, as
      found in other black populations.

PMID- 1396620
TI  - Cryptococcal meningitis in a young Ethiopian woman with AIDS.
AB  - The case of a 20 year old Ethiopian woman with cryptococcal meningitis and
      acquired immunodeficiency syndrome (AIDS) is presented. Though cryptococcal
      infections have been reported from many countries throughout the world, this is
      the first case reported from Ethiopia in a patient with the acquired
      immunodeficiency syndrome (AIDS). The clinical manifestations, diagnosis, and
      treatment are discussed, with a review of recent literature.

PMID- 1396621
TI  - Tetracycline versus penicillin in the treatment of louse-borne relapsing fever.
AB  - A prospective study of 120 louse-borne relapsing fever (LBRF) patient admitted to
      Mekele Regional Hospital, Tigray, Ethiopia from September to November 1991 was
      done. The patients were assigned systematically to a single dose of either
      tetracycline or procaine penicillin (sixty each). Doses given were oral
      tetracycline 250 mg or intramuscular procaine penicillin 200,000 units for
      children ages 12 years or less, and 500 mg or 600,000 IU for adults,
      respectively. The aim of this study was to compare the clinical effectiveness of
      tetracycline to that of procaine penicillin. Both drugs induced a Jarisch
      Herxheimer (JH) like reaction, which was clinically similar in the two treatment
      groups, but peaked later and was more prolonged in the patients treated with
      procaine penicillin. Spirochaetes cleared more slowly and relapses were noticed
      only in the procaine penicillin treated group. Thus, tetracycline is recommended
      as first choice therapy and a single dose is sufficient for treatment of LBRF
      patients.

PMID- 1396622
TI  - Anaesthesia for laser surgery.

PMID- 1396623
TI  - Sources of variability in halothane and caffeine contracture tests for
      susceptibility to malignant hyperthermia.
AB  - In vitro contracture tests for susceptibility to malignant hyperthermia (MH) were
      performed in 96 patients according to the protocol of the European MH Group. In
      addition, tests were performed with halothane 0.44 mmol l-1 and 0.66 mmol l-1,
      and caffeine 2 mmol l-1, each added as a single bolus dose to fresh specimens.
      For all tests the size of contractures were recorded, and for the diagnostic
      tests the halothane and caffeine threshold concentrations were determined (i.e.
      the minimal concentrations eliciting a contracture of 0.2 g). The caffeine
      specific concentration (CSC, i.e. the concentration increasing force 1.0 g) and
      the % increase with caffeine 2 mmol l-1 were calculated from the dose response
      curves. Various diagnostic criteria in use by the North American MH Group were
      applied, and diagnostic outcome compared with the result obtained by the protocol
      of the European MH Group. Thirty-five patients were susceptible to MH (MHS), 33
      were non-susceptible (MHN), and 28 had equivocal results of the tests (MHE).
      Additional tests were made in 34 MHS, 32 MHN, and 26 MHE patients. Contractures
      elicited by bolus addition of halothane or caffeine were significantly larger
      than those observed following the same dose of drug added cumulatively (P less
      than 0.05). Contractures greater than or equal to 0.7 g following halothane 3%
      (bolus dose) were seen in 78% of MHS patients and 18% of MHN patients, A CSC less
      than 4 mmol l-1 was elicited in 86% of MHS and 30% of MHN patients, whereas an
      increase in force greater than or equal to 4% or greater than or equal to 7% was
      seen in 71% and 34% of MHS patients, respectively, and in none of the MHN
      patients. Using the criterion of greater than or equal to 0.7 g in the halothane
      test and greater than or equal to 4% increase in the caffeine test gave the best
      agreement between diagnostic outcome with the European and North American
      protocols: All 34 MHS patients (100%) were positive to one or more tests, but so
      were eight of 32 MHN patients (25%), giving an overall diagnostic agreement of
      88%. We conclude that, in our laboratory, the results obtained with the two major
      protocols for investigation of MH susceptibility are not identical. Patients
      surviving fulminant MH, however, react abnormally to nearly all the tests. For
      validation and possibly further standardization of the tests each laboratory must
      investigate a large number of normal controls and as many patients surviving
      fulminant MH as possible.

PMID- 1396624
TI  - Midazolam-flumazenil vs. propofol in ambulatory ENT endoscopic procedures.
AB  - Two total intravenous anaesthesia techniques were compared in an open study of 80
      ambulatory patients undergoing ENT endoscopic procedures randomly assigned to two
      groups: Group I midazolam-flumazenil n = 40, Group II propofol n = 40. The mean
      doses including induction were 0.75 +/- 0.31 mg kg-1 h-1 for midazolam and 171 +/
      64 micrograms kg-1 min-1 for propofol for 46.3 +/- 17.7 min and 50.3 +/- 24.8
      min respectively. At the end of the procedure flumazenil 8.1 +/- 1.9 micrograms
      kg-1 was administered to Group I patients followed by a flumazenil continuous
      infusion at a minimal arousal rate (MAR) of 0.24 +/- 0.1 micrograms kg-1 min-1,
      and propofol discontinued in Group II patients. Baseline mean arterial pressure
      (MAP) and heart rate (HR) were similar in both groups and remained so during the
      procedure and recovery. In patients with cardiovascular disease, large variations
      (greater than or equal to 40% of baseline values) occurred more frequently in the
      propofol group whereas large variations in patients with no cardiovascular
      disease occurred more frequently in the midazolam group (P less than 0.05). Early
      recovery was more rapid after midazolam (P less than 0.05) whereas late criteria
      for recovery (maze and ambulation tests) were met more rapidly after propofol (P
      less than 0.05). It is concluded that with the midazolam-flumazenil sequence,
      early recovery is faster and haemodynamic stability better maintained in poor
      cardiovascular risk patients, whereas with propofol, street-fitness is more
      rapidly obtained, and haemodynamic stability better maintained in good risk
      patients.

PMID- 1396625
TI  - Respiratory dead space under anaesthesia in patients with mitral stenosis.
AB  - Physiological deadspace (VDphys) and arterial to end-tidal carbon dioxide tension
      difference [P(a-E)CO2] were calculated under anaesthesia in 27 patients with
      mitral stenosis planned for close mitral commissurotomy and in 15 healthy
      individuals for elective non-thoracic surgical procedures. A square wave
      inspiratory flow pattern and an end-inspiratory pause (25% and 10% of cycle time
      respectively) were given with a SERVO 900B ventilator used at respiratory rate of
      approximately 16 per min. An infra-red CO2 analyser was used to measure CO2
      production and end-tidal CO2 concentration. Measurements were made prior to the
      start of the surgery after a minimum of 10 min of stable ventilation to avoid the
      effect of surgery. Patients with multiple stenosis had significantly higher
      VDphys (4.28 +/- 1.02 ml kg-1 as compared to 2.10 +/- 0.52 ml kg-1 in controls, P
      less than 0.001), higher P(a-E)CO2 [0.43 +/- 0.51 kPa as compared to -0.02 +/-
      0.23 kPa, P less than 0.01] and lower respiratory system compliance (Crs). Peco2
      was positively correlated with PaCO2 in both groups (P less than 0.01). PaO2 was
      lower in mitral stenosis patients and P(A-a)O2 negatively correlated to Crs (P
      less than 0.01).

PMID- 1396626
TI  - Topical anaesthesia of the larynx: cocaine or lignocaine?
AB  - A double-blind, randomized study compared the cardiovascular responses and
      extubation conditions using lignocaine or cocaine for topical anaesthesia of the
      larynx. Absorption of both agents from the trachea was quantified by serial
      venous plasma concentrations. Serial blood pressure, ECG, O2 saturation and end
      tidal carbon dioxide measurements were obtained. Conditions at extubation were
      assessed on duration of coughing, graded on a scale of 1-4 (1 = no coughing, 2 =
      single cough, 3 = coughing lasting less than 30 s, 4 = coughing lasting 30 s or
      more). No difference was found in cardiovascular measurements between the two
      groups. The patterns of absorption of cocaine and lignocaine from the laryngeal
      mucosa were very similar, with peak absorption occurring at 10-15 min after
      laryngeal spraying. Although cocaine reduced the incidence of post-operative
      coughing when compared with lignocaine, this did not reach statistical
      significance.

PMID- 1396628
TI  - Effects of nimodipine administration during cardiopulmonary resuscitation in
      pigs.
AB  - The haemodynamic effects of nimodipine during cardiopulmonary resuscitation (CPR)
      were investigated in 25 anaesthetized pigs. After 5 min of ventricular
      fibrillation (VF) and 5 min of closed-chest CPR, adrenaline (50 micrograms kg-1),
      either nimodipine (10 micrograms kg-1 as a bolus followed by 1 microgram kg-1 min
      1 continuously) or the equivalent volume of placebo (solvent for nimodipine) were
      administered followed by the first countershock. If this failed to restore
      spontaneous circulation, adrenaline and countershocks were repeated for a maximum
      of 30 min. CPR was successful in nine out of 10 nimodipine-treated animals, but
      only in six out of 15 placebo-treated animals (P less than 0.02). In resuscitated
      pigs there were no significant differences in the number of countershocks, the
      number of seconds required for restoration of spontaneous circulation and the
      total doses of adrenaline required for both nimodipine and placebo pigs. After
      restoration of spontaneous circulation haemodynamic responses to nimodipine were
      characterized by decreases in systemic vascular resistance and mean arterial
      pressure with consequent increases in heart rate and cardiac output, but they
      were not significantly different from those of the placebo-treated animals. We
      therefore conclude that high doses of nimodipine are well tolerated during and
      after CPR; nimodipine administration may even result in higher initial CPR
      success rates. The underlying mechanisms need further investigation.

PMID- 1396627
TI  - Hydroxypropyl-beta-cyclodextrin can modulate the activity of spinally
      administered sufentanil.
AB  - Hydroxypropyl-beta-cyclodextrin increased the effectiveness of sufentanil after
      epidural and intrathecal administration in rats, both in terms of a longer
      duration of analgesia after a fixed dose of sufentanil, and in a reduction of the
      lowest ED50s to produce analgesia. There was also an increase in specificity, as
      indicated by the greater dissociation between the ED50s for analgesia and for
      supra-spinal side-effects. Maximal activity was measured after inclusion
      complexation of sufentanil in 10% hydroxypropyl-beta-cyclodextrin. At higher
      concentrations of hydroxypropyl-beta-cyclodextrin, both the activity and the
      specificity were attenuated. The increased safety of sufentanil in 10%
      hydroxypropyl-beta-cyclodextrin after spinal administration was also confirmed in
      terms of opioid-induced deviations in arterial PO2, PCO2 and oxygen saturation.
      At a dose of twice the ED50 for deep surgical analgesia, the
      sufentanil/hydroxypropyl-beta-cyclodextrin complex produced no changes in these
      parameters. With sufentanil alone at comparable analgesic doses, significant
      shifts in all three parameters were present immediately after drug
      administration. At higher concentrations of sufentanil in hydroxypropyl-beta
      cyclodextrin changes in the three blood gases were present but the deviations
      were always smaller than those observed with comparable doses of plain
      sufentanil. These results support the notion that after complexation sufentanil
      is present longer at the spinal level after spinal administration. As a
      consequence, there is less free sufentanil available for redistribution into
      lipid tissue and into the circulatory system, producing less systemic side
      effects.

PMID- 1396629
TI  - Post-operative muscle rigidity in an infant.

PMID- 1396630
TI  - Pentazocine and naloxone as part of an anaesthetic technique for the seriously
      ill.

PMID- 1396631
TI  - Normotensive normoxic men undergoing water diuresis fail to respond to
      stimulation of their peripheral arterial chemoreceptors by almitrine with an
      increase in plasma concentrations of atrial natriuretic factor.
AB  - The purpose of this study was to investigate the possible participation of atrial
      natriuretic factor (ANF) in the natriuretic and diuretic response occurring after
      stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate in
      normoxic humans. The experiments were performed in 14 healthy male volunteers
      undergoing water diuresis. Each subject participated in two experiments. In one
      of them they ingested 100-mg almitrine at 12 p.m. The other study served as a
      control. Surprisingly, our subjects responded to almitrine with an elevation of
      urine flow only, whereas sodium excretion remained almost unchanged over the
      whole period of the experiments. As regards ANF plasma concentrations, no
      statistically significant differences between the control and the almitrine group
      could be observed. Moreover, no direct connection between ANF plasma
      concentrations and renal volume excretion was detectable. We conclude that a
      specific stimulation of peripheral arterial chemoreceptors by almitrine in humans
      undergoing water diuresis did not seem to raise ANF plasma concentrations as is
      the case at high altitude. Therefore we would suggest that there exists no
      specific reflex influence of these receptors on ANF release.

PMID- 1396632
TI  - Scaling physiological measurements for individuals of different body size.
AB  - This paper examines how selected physiological performance variables, such as
      maximal oxygen uptake, strength and power, might best be scaled for subject
      differences in body size. The apparent dilemma between using either ratio
      standards or a linear adjustment method to scale was investigated by considering
      how maximal oxygen uptake (l.min-1), peak and mean power output (W) might best be
      adjusted for differences in body mass (kg). A curvilinear power function model
      was shown to be theoretically, physiologically and empirically superior to the
      linear models. Based on the fitted power functions, the best method of scaling
      maximum oxygen uptake, peak and mean power output, required these variables to be
      divided by body mass, recorded in the units kg 2/3. Hence, the power function
      ratio standards (ml.kg-2/3.min-1) and (W.kg-2/3) were best able to describe a
      wide range of subjects in terms of their physiological capacity, i.e. their
      ability to utilise oxygen or record power maximally, independent of body size.
      The simple ratio standards (ml.kg-1.min-1) and (W.kg-1) were found to best
      describe the same subjects according to their performance capacities or ability
      to run which are highly dependent on body size. The appropriate model to explain
      the experimental design effects on such ratio standards was shown to be log
      normal rather than normal. Simply by taking logarithms of the power function
      ratio standard, identical solutions for the design effects are obtained using
      either ANOVA or, by taking the unscaled physiological variable as the dependent
      variable and the body size variable as the covariate, ANCOVA methods.

PMID- 1396633
TI  - The power-duration product--evaluation of a new reference system for
      cardiopulmonary exercise testing.
AB  - The aim of this study was to assess the discriminatory power of the new reference
      system, power-duration product (PDP), for the analysis of haemodynamic and
      metabolic variables derived from cardiopulmonary exercise tests. The PDP was
      calculated as the cumulative index of the product of power (W) times the duration
      (minutes) of each individual exercise step. The study comprised 30 healthy male
      volunteers, who were classified into three groups with respect to their regular
      physical activity: 10 untrained medical students (students), 10 sprinters and
      long-jumpers (athletes) and 10 endurance athletes performing triathlon
      (triathletes). Twenty metabolic and haemodynamic variables were recorded
      throughout exhaustion-limited cycling ergometry. The data were analysed with
      respect to five reference systems (heart rate, relative and absolute oxygen
      consumption/body surface area, power, and PDP). A total of 14 differences between
      modified time courses of haemodynamic and metabolic variables in the three groups
      of volunteers were observed by reference to PDP, 12 by reference to relative
      oxygen consumption/body surface area, 11 by reference to heart rate, 8 by
      reference to absolute oxygen consumption/body surface area, and 7 by reference to
      power. When using PDP as the reference, the time courses of 8 parameters differed
      significantly between students and triathletes, 5 between students and athletes,
      and 1 between athletes and triathletes. In addition to its discriminatory
      superiority for the comparison of different groups characterized by different
      cardiopulmonary training and endurance, it was found that PDP permitted a better
      characterization of the individually performed exercise than the consideration of
      power per se.

PMID- 1396634
TI  - Effects of whole body microwave exposure on the rat brain contents of biogenic
      amines.
AB  - The effects of whole body microwave exposure on the central nervous system (CNS)
      of the rat were investigated. Rats weighing from 250 to 320 g were exposed for 1
      h to whole body microwave with a frequency of 2450 MHz at power densities of 5
      and 10 mW.cm-2 at an ambient temperature of 21-23 degrees C. The rectal
      temperatures of the rats were measured just before and after microwave exposure
      and mono-amines and their metabolites in various discrete brain regions were
      determined after microwave exposure. Microwave exposure at power densities of 5
      and 10 mW.cm-2 increased the mean rectal temperature by 2.3 degrees C and 3.4
      degrees C, respectively. The noradrenaline content in the hypothalamus was
      significantly reduced after microwave exposure at a power density of 10 mW.cm-2.
      There were no differences in the dopamine (DA) content of any region of the brain
      between microwave exposed rats and control rats. The dihydroxyphenyl acetic acid
      (DOPAC) content, the main metabolite of DA, was significantly increased in the
      pons plus medulla oblongata only at a power density of 10 mW.cm-2. The DA
      turnover rates, the DOPAC:DA ratio, in the striatum and cerebral cortex were
      significantly increased only at a power density of 10 mW.cm-2. The serotonin (5
      hydroxytryptamine, 5-HT) content in all regions of the brain of microwave exposed
      rats was not different from that of the control rats. The 5-hydroxyindoleacetic
      acid (5-HIAA) content in the cerebral cortex of microwave exposed rats was
      significantly increased at power densities of 5 and 10 mW.cm-2.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396636
TI  - Plasma ammonia is the principal source of ammonia in sweat.
AB  - Sweat contains ammonia. However, neither its source nor factors affecting its
      concentration in the sweat are known. The aim of this study was to examine the
      effect of plasma concentrations of ammonia and urea on the concentration of
      ammonia in the sweat. Four groups of male volunteers were examined: one control,
      two after ingestion of ammonium chloride, three cirrhotic, hyperammonaemic, four
      uraemic. Sweat was collected from each subject from the palmar side of the
      forearm using gauze pads, after previous iontophoresis of pilocarpine. Ammonia
      and urea concentrations were determined in the sweat and in the plasma. It was
      found that elevated plasma ammonia concentration in healthy subjects after
      ingestion of ammonium chloride as well in the cirrhotic patients resulted in an
      increase of ammonia concentration in the sweat. High plasma and sweat urea
      concentration in the uraemic subjects did not affect the concentration of ammonia
      in the sweat. It was concluded that plasma ammonia was the principal source of
      ammonia in the sweat.

PMID- 1396635
TI  - Physiological strain due to load carrying in heavy footwear.
AB  - To determine the effects of wearing heavy footwear on physiological responses
      five male and five female subjects were measured while walking on a treadmill (4,
      5.25, and 6.5 km.h-1) with different external loads (barefooted, combat boots,
      and waist pack). While walking without an external load the oxygen uptake, as a
      percentage of maximal oxygen uptake (%VO2max) of the men increased from 25%
      VO2max at 4 km.h-1 to 31% VO2max at 5.25 km.h-1 and to 42% VO2max at 6.5 km.h-1.
      The women had a significantly higher oxygen uptake of 30%, 40%, and 55% VO2max,
      respectively. In the most strenuous condition, walking at 6.5 km.h-1 with combat
      boots and waist pack (12 kg), the oxygen uptake for the men and women amounted to
      53% and 75% VO2max, respectively. The heart rate showed a similar response to the
      oxygen uptake, the women having a heart rate which was 15-40 beats.min-1 higher
      than that of the men, depending on the experimental condition. The perceived
      exertion was shown to be greatly dependent on the oxygen uptake. From the results
      a regression formula was calculated predicting the oxygen uptake depending on the
      mass of the footwear, walking speed and body mass. It was concluded that the mass
      of footwear resulted in an increase in the energy expenditure which was a factor
      1.9-4.7 times greater than that of a kilogram of body mass, depending on sex and
      walking speed.

PMID- 1396637
TI  - Influence of ageing on aerobic parameters determined from a ramp test.
AB  - The purpose of this study was to examine the four parameters of aerobic function,
      the maximum oxygen uptake (VO2max), ventilation threshold (ThVE), efficiency, and
      the effective time constant for oxygen consumption (tau'VO2), across age. In
      particular, the study was designed to observe whether there may be accelerated
      declines in aerobic function beyond 60 years of age. Seventy-nine sedentary men
      aged 30-84 years were studied. Each subject performed two maximal cycle ramp
      function tests, and data were collected on a breath-by-breath basis. The VO2max,
      from a plateau in VO2, was achieved in 87% of the subjects using the ramp test.
      The VO2max showed a significant decrease with increasing age (from linear
      regression, r = -0.81) at a rate averaging 0.037 l.min-1.year-1. The ThVE also
      declined with increasing age, but at a slower rate (0.013 l.min-1.year-1). The
      tau'VO2 was significantly increased across the age groups from 69 s for those
      aged 30-40 years to 98 s for those aged 60 years or more. There was no evidence
      of accelerated decline in these aerobic parameters beyond age 60 years, and there
      were no differences in efficiency (27.5-29.9%) across age. Although other forcing
      functions should be used to confirm this characterization of the oxygen kinetics,
      this slowed response with age would result in greater oxygen deficit and possibly
      earlier fatigue in response to even light exercise in older individuals.

PMID- 1396638
TI  - Physiological responses to maximal intensity intermittent exercise.
AB  - Physiological responses to repeated bouts of short duration maximal-intensity
      exercise were evaluated. Seven male subjects performed three exercise protocols,
      on separate days, with either 15 (S15), 30 (S30) or 40 (S40) m sprints repeated
      every 30 s. Plasma hypoxanthine (HX) and uric acid (UA), and blood lactate
      concentrations were evaluated pre- and postexercise. Oxygen uptake was measured
      immediately after the last sprint in each protocol. Sprint times were recorded to
      analyse changes in performance over the trials. Mean plasma concentrations of HX
      and UA increased during S30 and S40 (P less than 0.05), HX increasing from 2.9
      (SEM 1.0) and 4.1 (SEM 0.9), to 25.4 (SEM 7.8) and 42.7 (SEM 7.5) mumol.l-1, and
      UA from 372.8 (SEM 19) and 382.8 (SEM 26), to 458.7 (SEM 40) and 534.6 (SEM 37)
      mumol.l-1, respectively. Postexercise blood lactate concentrations were higher
      than pretest values in all three protocols (P less than 0.05), increasing to 6.8
      (SEM 1.5), 13.9 (SEM 1.7) and 16.8 (SEM 1.1) mmol.l-1 in S15, S30 and S40,
      respectively. There was no significant difference between oxygen uptake
      immediately after S30 [3.2 (SEM 0.1) l.min-1] and S40 [3.3 (SEM 0.4) l.min-1],
      but a lower value [2.6 (SEM 0.1) l.min-1] was found after S15 (P less than 0.05).
      The time of the last sprint [2.63 (SEM 0.04) s] in S15 was not significantly
      different from that of the first [2.62 (SEM 0.02) s]. However, in S30 and S40
      sprint times increased from 4.46 (SEM 0.04) and 5.61 (SEM 0.07) s (first) to 4.66
      (SEM 0.05) and 6.19 (SEM 0.09) s (last), respectively (P less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396639
TI  - Oxygen uptake during running as related to body mass in circumpubertal boys: a
      longitudinal study.
AB  - To investigate the effect of endurance training on physiological characteristics
      during circumpubertal growth, eight young runners (mean starting age 12 years)
      were studied every 6 months for 8 years. Four other boys served as untrained
      controls. Oxygen uptake (VO2) and blood lactate concentrations were measured
      during submaximal and maximal treadmill running. The data were aligned with each
      individual's age of peak height velocity. The maximal oxygen uptake (VO2max;
      ml.kg-1.min-1) decreased with growth in the untrained group but remained almost
      constant in the training group. The oxygen cost of running at 15 km.h-1 (VO2 15,
      ml.kg-1.min-1) was persistently lower in the trained group but decreased
      similarly with age in both groups. The development of VO2max and VO2 15 (l.min-1)
      was related to each individual's increase in body mass so that power functions
      were obtained. The mean body mass scaling factor was 0.78 (SEM 0.07) and 1.01
      (SEM 0.04) for VO2max and 0.75 (SEM 0.09) and 0.75 (SEM 0.02) for VO2 15 in the
      untrained and trained groups, respectively. Therefore, expressed as ml.kg
      0.75.min-1, VO2 15 was unchanged in both groups and VO2max increased only in the
      trained group. The running velocity corresponding to 4 mmol.l-1 of blood lactate
      (nu la4) increased only in the trained group. Blood lactate concentration at
      exhaustion remained constant in both groups over the years studied. In
      conclusion, recent and the present findings would suggest that changes in the
      oxygen cost of running and VO2max (ml.kg-1.min-1) during growth may mainly be due
      to an overestimation of the body mass dependency of VO2 during running.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396641
TI  - Increased working capacity with hyperoxia in humans.
AB  - The purpose of the study was to examine the influence of oxygen-breathing on
      maximal oxygen uptake (VO2max) and submaximal endurance performance. Six young
      women and five men rode a cycle-ergometer while breathing compressed air
      (normoxia, NOX) or a 55% O2 in N2 mixture (hyperoxia, HOX). The VO2max increased
      significantly by 12% (P less than 0.01) with HOX in the women but not in the men
      (+4%; nonsignificant). Maximal heart rate was also increased with HOX in the
      women but not in the men. Endurance time during work to exhaustion at 80% of
      normoxic VO2max was 41% longer in HOX than in NOX (P less than 0.025) with no
      significant difference between the men and the women. The variation among
      individuals was large. The oxygen uptake and respiratory quotient were not
      different in the two endurance tests, but pulmonary ventilation (VE) and blood
      lactate concentration were lower in HOX than in NOX, especially during the latter
      part of the task. Plasma base deficit (BDpl) increased initially by 3.5 mmol.l-1
      during HOX and then stabilized. In NOX, a continuous increase was seen and the
      change was more than twice as large. Relative to BDpl, VE was higher in HOX than
      in NOX indicating a more efficient ventilatory compensation of the metabolic
      acidosis. The reduced ventilatory demand and lower metabolic acidosis in HOX in
      combination with lower relative exercise intensity may have contributed to the
      longer time to exhaustion. However, the pattern of individual variation suggested
      that other mechanisms were also involved.

PMID- 1396640
TI  - Adaptations in skeletal muscle capillarity following changes in oxygen supply and
      changes in oxygen demands.
AB  - The effects of changes in oxygen supply and oxygen demands on fiber cross
      sectional areas, capillary densities and capillary to fiber ratios were
      determined in three skeletal muscles of rat. The muscles examined were the vastus
      lateralis, soleus, and diaphragm. Reduced oxygen supply was produced by
      subjecting rats to ambient hypoxia, and increased oxygen demands were produced by
      subjecting rats to low ambient temperatures or treatment with thyroxin.
      Capillaries were visualized by injecting fluorescent dyes into the circulation.
      Muscles were quick frozen at resting lengths to preserve normal fiber geometry
      and were subsequently sectioned on a cryostat. All of the muscles sampled from
      animals in the experimental groups had elevated capillary densities. However,
      capillary to fiber ratios were not increased significantly in any muscle, for any
      experimental condition. Thus, all of the observed differences in capillarity were
      due to changes in the intrinsic rate of muscle fiber growth. Further, the
      relations of capillary density and capillary to fiber ratio to fiber area were
      the same as those obtained during normal maturation, suggesting that capillary
      growth is closely linked to the intrinsic rate of fiber growth.

PMID- 1396642
TI  - Intramuscular pressures during exercise: an evaluation of a fiber optic
      transducer-tipped catheter system.
AB  - The efficacy of a modified fibre optic transducer-tipped catheter system for
      measuring intramuscular pressures during exercise was determined. A
      microcapillary infusion technique using a catheter was employed as the standard
      of comparison due to its established dynamic properties. Pressures were measured
      in the tibialis anterior muscle of six healthy adults at rest before exercise,
      during isometric and concentric exercise, and at rest after exercise. The fibre
      optic system measured contraction pressures equal to the microcapillary infusion
      technique during all phases of the exercise protocols but recorded a lower
      relaxation pressure during isometric exercise and a lower rest pressure following
      20 min of concentric exercise. Negative relaxation pressures were recorded by the
      fibre optic system for two subjects during continuous concentric exercise. It is
      hypothesized that a piston effect, due to the sliding of muscle fibres at the
      catheter tip following a contraction, rendered falsely low pressures during
      relaxation and that this artefact was reflected in the subsequent rest pressure
      following exercise. The larger volume (157 mm3) and area (3.49 mm2) of the fibre
      optic catheter in the muscle made it more prone to this effect than the
      conventional catheter (39 mm3 and 0.87 mm2, respectively). The fibre optic system
      may be preferred when recording the muscle contraction pressures during complex
      limb movements but should not be used when assessing the relaxation pressures or
      the pressure at rest following exercise.

PMID- 1396643
TI  - Caffeine increases maximal anaerobic power and blood lactate concentration.
AB  - The aim of this study was to specify the effects of caffeine on maximal anaerobic
      power (Wmax). A group of 14 subjects ingested caffeine (250 mg) or placebo in
      random double-blind order. The Wmax was determined using a force-velocity
      exercise test. In addition, we measured blood lactate concentration for each load
      at the end of pedalling and after 5 min of recovery. We observed that caffeine
      increased Wmax [964 (SEM 65.77) W with caffeine vs 903.7 (SEM 52.62) W with
      placebo; P less than 0.02] and blood lactate concentration both at the end of
      pedalling [8.36 (SEM 0.95) mmol.l-1 with caffeine vs 7.17 (SEM 0.53) mmol.l-1
      with placebo; P less than 0.01] and after 5 min of recovery [10.23 (SEM 0.97)
      mmol.l-1 with caffeine vs 8.35 (SEM 0.66) mmol.l-1 with placebo; P less than
      0.04]. The quotient lactate concentration/power (mmol.l-1.W-1) also increased
      with caffeine at the end of pedalling [7.6.10(-3) (SEM 3.82.10(-5)) vs 6.85.10(
      3) (SEM 3.01.10(-5)); P less than 0.01] and after 5 min of recovery [9.82.10(-3)
      (SEM 4.28.10(-5)) vs 8.84.10(-3) (SEM 3.58.10(-5)); P less than 0.02]. We
      concluded that caffeine increased both Wmax and blood lactate concentration.

PMID- 1396644
TI  - Oxygen uptake during swimming in a hypobaric hypoxic environment.
AB  - The purpose of this study was to determine oxygen uptake (VO2) at various water
      flow rates and maximal oxygen uptake (VO2max) during swimming in a hypobaric
      hypoxic environment. Seven trained swimmers swam in normal [N; 751 mmHg (100.1
      kPa)] and hypobaric hypoxic [H; 601 mmHg (80.27 kPa)] environments in a chamber
      where atmospheric pressure could be regulated. Water flow rate started at 0.80
      m.s-1 and was increased by 0.05 m.s-1 every 2 min up to 1.00 m.s-1 and then by
      0.05 m.s-1 every minute until exhaustion. At submaximal water flow rates, carbon
      dioxide production (VCO2), pulmonary ventilation (VE) and tidal volume (VT) were
      significantly greater in H than in N. There were no significant differences in
      the response of submaximal VO2, heart rate (fc) or respiratory frequency (fR)
      between N and H. Maximal VE, fR, VT, fc, blood lactate concentration and water
      flow rate were not significantly different between N and H. However, VO2max under
      H [3.65 (SD 0.11) l.min-1] was significantly lower by 12.0% (SD 3.4)% than that
      in N [4.15 (SD 0.18) l.min-1]. This decrease agrees well with previous
      investigations that have studied centrally limited exercise, such as running and
      cycling, under similar levels of hypoxia.

PMID- 1396645
TI  - Phosphorus-31 nuclear magnetic resonance study on the effects of endurance
      training in rat skeletal muscle.
AB  - To evaluate changes in muscle energetics following endurance training, we
      measured phosphorus-31 nuclear magnetic resonance (31P NMR) spectra on rat muscle
      in vivo before and after training in the same animals. The endurance training
      lasted for 3 months. The 31P NMR spectra were obtained serially at rest, during
      exercise by electrical stimulation, and during recovery. Intramuscular
      phosphocreatine (PCr), inorganic phosphate (P(i)), adenosine 5'-triphosphate
      (ATP) and pH were determined from the NMR spectra. The ratio of PCr:(PCR + P(i)
      at rest showed no difference between the trained and control groups even after 3
      months of training. During exercise, however, this ratio was significantly higher
      in the trained group than in the control group. The ratio also recovered more
      rapidly after exercise in the trained group. The intramuscular pH decreased
      slightly by approximately 0.1 pH unit during exercise but did not show a
      significant difference between the groups. These results indicated that endurance
      training of 3 months duration improved the ATP supply system in the muscle. They
      also demonstrated that 31P NMR is a potent method for evaluating the effects of
      training in the same individuals.

PMID- 1396646
TI  - Comparison of heart rate monitoring combined with indirect calorimetry and the
      doubly labelled water (2H2(18)O) method for the measurement of energy expenditure
      in children.
AB  - The aim of the present study was to compare data on 24-h energy expenditure
      (EE24h) in nine boys and ten girls (mean age 9.3 and 8.1 years, respectively) by
      heart rates (fc) combined with energy expenditure obtained from a 1-day stay in
      an indirect calorimeter (EEcal) and a 2-week period of normal living using the
      doubly labelled water method (EEdlw). Individual calibration curves were derived
      from fc and oxygen uptake measured during sleep (in the calorimeter), standing
      and walking on a treadmill. An estimation of energy expenditure based on 24-h fc
      monitoring (EEfc) was made during the stay in the calorimeter and on a normal
      school-day. Mean results showed an overestimation in EEfc compared to EEcal and
      EEdlw of 10.4% and 12.3% respectively, varying from 6.3% to 16.2%. These results
      confirmed earlier observations in adults that for a group the fc method
      overestimates EE24h by about 10%.

PMID- 1396647
TI  - Cardiorespiratory adaptation with short term training in older men.
AB  - The purpose of this study was to assess the rate of training-induced
      cardiorespiratory adaptations in older men [mean (SD), 66.5 (1.2) years]. The
      eight subjects trained an average of 4.3 (0.3) times each week. The walk/jog
      training was in two phases with 4 weeks (phase 1) at a speed to elicit 70% of pre
      training maximal oxygen consumption (VO2max), and 5 weeks (phase 2) at 80%.
      Maximal exercise treadmill tests and a standardized submaximal protocol were
      performed prior to training, at weekly intervals during the training programme,
      and after training. VO2max (ml.kg-1.min-1) increased significantly over both
      phases: 6.6% after the first 4 weeks, and an additional 5.2% after the final 5
      weeks. The weekly changes in VO2max over phase 1 were well fitted by an
      exponential association curve (r = 0.75). The half-time for the rate of
      adaptation was 13.8 days, or 8.3 training sessions. Over phase 2, the change in
      VO2max did not plateau and a time course could not be determined. Submaximal
      exercise heart rate (fc) was reduced a significant 10 beats.min-1 after the first
      4 weeks, and further 6 beats.min-1 over the final 5 weeks. The fc reductions
      showed half-times of 9.1 days (phase 1) and 9.8 days (phase 2) (or 5-6 training
      sessions). The anaerobic ventilation threshold was increased 13.9% over the 9
      weeks of training and the respiratory exchange ratio during constant load heavy
      exercise was significantly reduced; however, these changes could not be described
      by an exponential time course. Thus, short-term exercise training of older men
      resulted in significant and rapid cardiorespiratory improvements.

PMID- 1396648
TI  - Blood ammonia and lactate concentrations during endurance exercise of differing
      intensities.
AB  - The purpose of this study was to examine the changes of blood ammonia
      concentration ([NH3]b) during endurance exercise of differing intensities on the
      cycle ergometer and to compare [NH3]b to the changes observed in the
      simultaneously monitored blood lactate acid concentrations ([la-]b) measurements.
      A group of 16 endurance-trained athletes participated in the first part of the
      study and performed exercise of 30 min duration in a randomized order at
      intensities of 85%, 95%, 100% and 105% of their individual anaerobic threshold
      (Th(an,ind); E85-E105) which had been determined beforehand by a cycle exercise
      test with stepwise increments in intensity. In the second part, 18 average
      endurance-trained sports students underwent exhausting intensive endurance
      exercise (IEE) with an intensity of 95% of Th(an,ind). An extensive endurance
      exercise (EEE) of the same duration at 85% of the Th(an,ind) was carried out 2
      days later. The [NH3]b increased constantly with increasingly duration of all
      exercise. However, [la-]b only increased during exercise with intensities above
      the Th(an,ind) (E105). The increase of [NH3]b was higher with higher exercise
      intensities. At IEE, [NH3]b was significantly higher from the 30th min than at
      EEE, whereas [la-]b increased from the 5th min. In conclusion, [la-]b responded
      more sensitively to the intensity of exercise than [NH3]b, but it is conceivable
      that in the future measurements of [NH3]b could be used to advise on the duration
      of endurance training. At present, however, the lack of experience and lack of
      appropriate values still hinders the systematic use of [NH3]b measurements in the
      physiological monitoring of sports training.

PMID- 1396649
TI  - Effect of heat stress on muscle blood flow during dynamic handgrip exercise.
AB  - During exercise in a hot environment, blood flow in the exercising muscles may be
      reduced in favour of the cutaneous circulation. The aim of our study was to
      examine whether an acute heat exposure (65-70 degrees C) in sauna conditions
      reduces the blood flow in forearm muscles during handgrip exercise in comparison
      to tests at thermoneutrality (25 degrees C). Nine healthy men performed dynamic
      handgrip exercise of the right hand by rhythmically squeezing a water-filled
      rubber tube at 13% (light), and at 34% (moderate) of maximal voluntary
      contraction. The left arm served as a control. The muscle blood flow was
      estimated as the difference in plethysmographic blood flow between the exercising
      and the control forearm. Skin blood flow was estimated by laser Doppler flowmetry
      in both forearms. Oesophageal temperature averaged 36.92 (SEM 0.08) degrees C at
      thermoneutrality, and 37.74 (SEM 0.07) degrees C (P less than 0.01) at the end of
      the heat stress. The corresponding values for heart rate were 58 (SEM 2) and 99
      (SEM 5) beats.min-1 (P less than 0.01), respectively. At 25 degrees C, handgrip
      exercise increased blood flow in the exercising forearm above the control forearm
      by 6.0 (SEM 0.8) ml.100 ml-1.min-1 during light exercise, and by 17.9 (SEM 2.5)
      ml.100 ml-1.min-1 during moderate exercise. In the heat, the increases were
      significantly higher: 12.5 (SEM 2.2) ml.100 ml-1.min-1 at the light exercise
      level (P less than 0.01), and 32.2 (SEM 5.9) ml.100 ml-1.min-1 (P less than 0.05)
      at the moderate exercise level.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396650
TI  - Reproducibility of isokinetic leg strength and endurance characteristics of adult
      men and women.
AB  - Day-to-day variability and single-measurement reliability of selected isokinetic
      knee extension-flexion strength and endurance indices were assessed in 10 adult
      men and 8 adult women. On three occasions separated by at least 5 days, the
      subjects completed 4 reciprocal maximal voluntary contractions (MVC) at different
      angular velocities (1.05 rad.s-1 and 3.14 rad.s-1). The men also completed a
      muscular endurance test consisting of 30 reciprocal, MVC at 3.14 rad.s-1.
      Coefficient of variation, intra-class correlation coefficient and standard error
      of single-measurement scores support the continued use of gravity corrected peak
      torque (PT) and average peak torque (APT) as indices of isokinetic leg strength.
      Similarly, gravity corrected APT and total work should be the recommended indices
      of isokinetic leg muscular endurance in men. The results suggest that these
      isokinetic indices must be assessed using multiple day-to-day trial protocols
      adequately to describe performance capacity. Composite indices such as the ratio
      of Knee flexion to extension PT and fatigue measurements offer considerably
      reduced reliability and a greater potential for misinterpretation. The
      reliability of knee extension indices generally exceeds that of flexion indices.
      Similar variability and reproducibility of responses were observed between men
      and women and between reciprocal contractions performed at angular velocities of
      1.05 rad.s-1 and 3.14 rad.s-1.

PMID- 1396651
TI  - Stimulation frequency and force potentiation in the human adductor pollicis
      muscle.
AB  - The effect of stimulation frequency on twitch force potentiation was examined in
      the adductor pollicis muscle of ten normal subjects. The ulnar nerve was
      supramaximally stimulated at the wrist and isometric twitch force was measured
      from a 3-Hz train lasting 1 s. Test stimulation frequencies of 5, 10, 20, 25, 30,
      40, 50 and 100 Hz were applied for 5 s each in random order (5 min apart) and the
      twitches (3 Hz) were applied immediately before and after (1 s) the test
      frequency and at intervals up to 5 min afterwards (10 s, and 1, 2 and 5 min).
      Poststimulation twitches were expressed as a percentage of the prestimulation
      twitch. Low frequency fatigue was not induced by the protocol since the 20:50 Hz
      ratio did not alter within each session. The degree of twitch potentiation was
      frequency dependent, with potentiation increasing up to 50 Hz [mean 173 (SD 16)%]
      but the effect was markedly less at 100 Hz [mean 133 (SD 25)%, P less than 0.01]
      for all subjects. The reduced potentiation at 100 Hz may have occurred due to
      high frequency fatigue produced by the 100-Hz test stimulation train. The optimal
      frequency of those examined in the experimental group was 50 Hz but this only
      produced maximal potentiation in six of the ten subjects and 100 Hz always
      produced less potentiation. These findings have implications for electrical
      stimulation of muscle in the clinical setting.

PMID- 1396652
TI  - Changes in ventilation at the start and end of moderate and heavy exercise of
      short and long duration.
AB  - These experiments examined the effect of exercise intensity and duration on the
      magnitude of the abrupt change in ventilation at the start (VE,start) and end
      (VE,end) of exercise. Five subjects performed constant load treadmill exercise at
      50% and 80% of their maximum oxygen consumption (VO2max) for 6 and 10 min while
      inspiring atmospheric air. The subjects also completed additional exercise tests
      at 80% VO2max for 10 min while inspiring an oxygen-enriched gas mixture. During
      each exercise trial ventilation was measured breath-by-breath. The VE,start and
      VE,end were determined by using non-linear curve-fitting techniques. The results
      showed that VE,start was greater at the start of the 80-% exercise tests compared
      to the 50-% tests and that VE,start at each level of exercise was greater than
      VE,end. The results also demonstrated that VE,end was inversely related to the
      intensity and duration of exercise. Furthermore, the VE,end was not altered
      subsequent to the inspiration of oxygen-enriched air. These findings have led us
      to postulate that the stimulus responsible for VE,start is reduced during
      exercise and that the degree of reduction is related to the intensity and
      duration of exercise. In addition, it was concluded that these changes might
      occur independently of peripheral chemoreceptor activity.

PMID- 1396653
TI  - The influence of moving auditory fields on postural sway behaviour in man.
AB  - Postural sway behaviour was assessed, using a standard biomechanical measuring
      platform, in 30 young subjects (15 men, 15 women) during 60 s of erect standing
      in various combinations of visual input and moving auditory fields. The sway
      parameters investigated were mean lateral, antero-posterior, radius and velocity
      of sway, the area within the sway profile and the length of the sway path. The
      findings support the view that moving auditory fields have a destabilising
      influence on postural sway behaviour, and suggest that under the appropriate
      conditions postural sway can be "driven" by the auditory environment.

PMID- 1396654
TI  - Relationship between plasma ammonia and blood lactate concentrations after
      maximal treadmill exercise in circumpubertal girls and boys.
AB  - The purpose of the study was to define a relationship between plasma ammonia
      [NH3]pl and blood lactate concentrations [la-]b after exercise in children and to
      find out whether the [NH3]pl, determined during laboratory treadmill tests, may
      be useful as a predictor of the children's sprint running ability. A group of 20
      girls and 14 boys trained in athletics or swimming and 8 untrained boys, aged
      13.2 to 13.7 years, participated in the study. Their [NH3]pl and [la-]b were
      measured before and after incremental maximal treadmill exercise. In addition,
      the subjects' running performance was tested in 30-, 60- and 600- or 1000-m runs
      under field conditions. The [NH3]pl during the treadmill runs increased by 20.1
      (SD 17.3), 24 (SD 16.7) and 10 (SD 4.3) mumol.l-1 in the girls, the trained boys
      and the untrained boys, respectively. The postexercise [NH3]pl correlated
      positively with [la-]b (r = 0.565 in the girls and 0.812 in the boys) and
      treadmill speed attained during the test (r = 0.489 in the girls and 0.490 in the
      boys). Significant correlations were also found between [NH3]pl obtained during
      the treadmill test and the times of 30- and 60-m runs (r = -0.676 and -0.648,
      respectively) in the boys but not in the girls. A comparison of the present data
      with those reported previously in adults showed that increases in [NH3]pl during
      maximal exercise in children would seem to be lower than in adult subjects both
      in absolute values and in relation to [la-]b.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396655
TI  - Electromyographic changes in work-related myalgia of the trapezius muscle.
AB  - In 11 patients, all women, 21-55 years of age, with unilateral work-related
      myalgia of the trapezius muscle, the right and left trapezius muscles were
      examined simultaneously for electromyogram (EMG) signs of localized muscle
      fatigue. All patients were tested with 0-kg hand load for 5 min, holding the arms
      straight at 90 degrees of elevation in the scapular plane. Only 4 of the patients
      tolerated exposure to higher load levels. They were tested with 1 kg hand load
      for 3 min and 2 kg hand load for 2 min, with a period of rest of 30 min between
      the trials. The EMG mean power frequency (MPF) and root mean square (rms) were
      calculated. Data were normalized with the initial value as a reference and
      regression analyses were performed. On both sides a decrease of MPF and an
      increase of rms were found with increasing time and load, i.e. classical EMG
      signs of localized muscle fatigue. Compared with the nonaffected side smaller
      changes were found on the affected side, possibly due to pain inhibition,
      impaired microcirculation and biochemical changes along the muscle fibres. At 0
      kg hand load we found no change of MPF on either side despite subjective feelings
      of fatigue and pain. We interpreted these findings as an indication of reduced
      capacity of the affected trapezius muscle to sustain static load with early
      development of pain-associated local fatigue.

PMID- 1396656
TI  - Assessment of skeletal muscle damage in successive biopsies from strength-trained
      and untrained men and women.
AB  - The effects of repeated biopsy sampling on muscle morphology was qualitatively
      and quantitatively assessed in strength-trained and untrained men and women.
      College-age men (13) and women (8) resistance trained twice a week for 8 weeks. A
      progressive resistance-training program was performed consisting of squats, leg
      presses, and leg extensions. Nontraining men (7) and women (5) served as
      controls. Muscle biopsy specimens and fasting bloods were obtained at the
      beginning and every 2 weeks and histochemical, biochemical, and ultrastructural
      methods were employed to assess the type and amount of damage. Except for a few
      scattered atrophic fibers in 2 of the 33 biopsy samples, all initial specimens
      were normal. In contrast, many of the subsequent biopsy samples from both
      untrained and resistance-trained men and women contained evidence of damage.
      Ultrastructural analysis confirmed that degenerative-regenerative processes were
      occurring in both groups. However, training subjects had a four-fold greater
      number of damaged fibers than nontraining subjects (8.53% vs 2.08%). In addition,
      only biopsy samples from training individuals contained fibers with internal
      disorganization (e.g., Z-line streaming, myofibrillar disruption). Calpain II
      levels in the biopsy samples and serum creatine kinase activity were not
      significantly affected supporting the light and electron microscopic observations
      that most of the damaged fibers were normal in appearance except for their small
      diameter. In summary, focal damage induced by the biopsy procedure is not
      completely repaired after 2 weeks and could affect the results, particularly
      cross-sectional area measurements. Moreover, resistance training appears to cause
      additional damage to the muscle and may delay repair of the biopsied region.

PMID- 1396657
TI  - Thermal responses of men and women during cold-water immersion: influence of
      exercise intensity.
AB  - The influence of exercise intensity on thermoregulation was studied in 8 men and
      8 women volunteers during three levels of arm-leg exercise (level I: 700 ml
      oxygen (O2).min-1; level II: 1250 ml O2.min-1; level III: 1700 ml O2.min-1) for 1
      h in water at 20 and 28 degrees C (Tw). For the men in Tw 28 degrees C the rectal
      temperature (Tre) fell 0.79 degree C (P less than 0.05) during immersion in both
      rest and level-I exercise. With level-II exercise a drop in Tre of 0.54 degree C
      (P less than 0.05) was noted, while at level-III exercise Tre did not change from
      the pre-immersion value. At Tw of 20 degrees C, Tre fell throughout immersion
      with no significant difference in final Tre observed between rest and any
      exercise level. For the women at rest at Tw 28 degrees C, Tre fell 0.80 degree C
      (P less than 0.05) below the pre-immersion value. With the two more intense
      levels of exercise Tre did not decrease during immersion. In Tw 20 degrees C, the
      women maintained higher Tre (P less than 0.05) during level-II and level-III
      exercise compared to rest and exercise at level I. The Tre responses were related
      to changes in tissue insulation (I(t)) between rest and exercise with the largest
      reductions in I(t) noted between rest and level-I exercise across Tw and gender.
      For mean and women of similar percentage body fat, decreases in Tre were greater
      for the women at rest and level-I exercise in Tw 20 degrees C (P less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396658
TI  - Adenine nucleotide degradation in the thoroughbred horse with increasing exercise
      duration.
AB  - Adenine nucleotide (AN) degradation has been shown to occur during intense
      exercise in the horse and in man, at or close to the point of fatigue. The aim of
      the study was to compare the concentrations of muscle inosine 5'-monophosphate
      (IMP) and plasma ammonia (NH3) during intense exercise with the concentrations of
      muscle and blood lactate. Seven trained thoroughbred horses were used in the
      study. Each exercised on a treadmill for periods of between 30 s and 150 s, at 11
      and/or 12 m.s-1. Blood and muscle samples were taken and analysed for lactate and
      NH3 and adenosine 5'-triphosphate (ATP), phosphorylcreatine (PCr), IMP, creatine,
      lactate and glycerol-3-phosphate respectively. Horses showed varying degrees of
      AN degradation as indicated by plasma [NH3] and muscle [ATP] and [IMP].
      Comparisons of [IMP] with muscle [lactate], and plasma [NH3] with that of blood
      [lactate] indicated a threshold to the start of AN degradation. This threshold
      corresponded to a lactate content of around 80 mmol.kg-1 dry muscle and 15 mmol.l
      1 in blood. We discuss the mechanisms which have been proposed to account for AN
      degradation and suggest that IMP formation occurs as a result of a sudden rise in
      the concentration of adenosine 5'-diphosphate (ADP) and consequently the
      concentration of adenosine 5'-monophosphate. The data suggest a critical pH below
      which there may be a substantial reduction in the kinetics of ADP
      rephosphorylation provided by PCr resulting in an increase in [ADP], which is the
      stimulus to AN degradation during intense exercise.

PMID- 1396659
TI  - Changes in haemorheology in the racing greyhound as related to oxygen delivery.
AB  - Arterial blood samples were obtained from six greyhounds during rest, immediately
      before, and after a 704-m (7/16th mile) race. Measurements were made of various
      haematological (red cell count, haemoglobin, packed cell volume, white cell
      count, plasma proteins) and haemorheological variables. Blood and plasma
      viscosity were determined at high wall shear stresses (67-200 dynes.cm-2, 670
      2000 microN.cm-2) in a 20-microns glass capillary device which was designed to
      take the diameter dependence of blood viscosity (Fahraeus-Lindqvist effect) into
      account. Compared to values at rest, substantial haemoconcentration occurred
      before the race, mainly due to splenic discharge of red cells. Additional
      haemoconcentration was found after the race. The increase of effective blood
      viscosity caused by elevation of packed cell volume was greater than the increase
      in O2 binding capacity resulting from the elevated haemoglobin concentration,
      suggesting that the haemoconcentration observed in the exercising greyhound does
      not enhance O2 delivery to skeletal muscle. The main physiological effect of red
      cell discharge from the contracting spleen appeared to be a consequence of the
      volume rather than the composition of the circulating blood.

PMID- 1396660
TI  - How should body heat storage be determined in humans: by thermometry or
      calorimetry?
AB  - The aim of this study was to determine whether in humans there are differences in
      the heat storage calculated by partitional calorimetry (S, the balance of heat
      gains and heat losses) compared to the heat storage obtained by conventional
      methods (thermometry) via either core temperature or mean body temperatures (Tb =
      0.8Tc + 0.2Tsk, where Tc is core temperature and Tsk is mean skin temperature)
      when two different sites are used as an index of Tc [rectal (T(re)) and auditory
      canal (T(ac)) temperatures]. Since women respond to the heat differently than
      men, both sexes were studied. After a stabilisation period at thermal neutrality,
      six men and seven women were exposed to a globe temperature of 50 degrees C,
      relative humidity of 17% and wind speed of 0.8-1.0 m.s-1 for 90 min semi-nude at
      rest, where T(re), T(ac), Tsk, metabolic rate, dry (radiant + convective heat
      exchange) and evaporative heat losses, S, heat storage by Tc (STc) and heat
      storage by Tb (STb) were assessed every minute. In the mean, S was equal to
      350.8(SEM 49.6) kJ whereas STc amounted to only 114.6(SEM 16.2) and 196.7(SEM
      32.3) kJ for T(re) and T(ac), respectively (P less than 0.05). Final STb(re)
      underestimated S by 49% [177.7(SEM 23.0) kJ; P less than 0.05] whereas STb(ac)
      was not significantly different than S [255.7(SEM 37.9) kJ]. In the women, S
      corresponded to a total of 294.3(SEM 23.2) kJ, a value that was very similar to
      the STb(ac) [262.6(SEM 31.0) kJ], whereas STb(re) under-predicated S by 35%
      [190.4(SEM 26.3) kJ; P less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396661
TI  - The protein kinase C family.
AB  - Protein kinase C represents a structurally homologous group of proteins similar
      in size, structure and mechanism of activation. They can modulate the biological
      function of proteins in a rapid and reversible manner. Protein kinase C
      participates in one of the major signal transduction systems triggered by the
      external stimulation of cells by various ligands including hormones,
      neurotransmitters and growth factors. Hydrolysis of membrane inositol
      phospholipids by phospholipase C or of phosphatidylcholine, generates sn-1,2
      diacylglycerol, considered the physiological activator of this kinase. Other
      agents, such as arachidonic acid, participate in the activation of some of these
      proteins. Activation of protein kinase C by phorbol esters and related compounds
      is not physiological and may be responsible, at least in part, for their tumor
      promoting activity. The cellular localization of the different calcium-activated
      protein kinases, their substrate and activator specificity are dissimilar and
      thus their role in signal transduction is unlike. A better understanding of the
      exact cellular function of the different protein kinase C isoenzymes requires the
      identification and characterization of their physiological substrates.

PMID- 1396662
TI  - The cytoskeletal lattice of muscle cells.

PMID- 1396663
TI  - Ring-substituted diaqua(1,2-diphenylethylenediamine)platinum(II) sulfate reacts
      with DNA through a dissociable complex.
AB  - Ring-substituted diaqua(1,2-diphenylethylenediamine)platinum(II) sulfate shows
      unusual kinetics in its reaction with salmon testis DNA. The mechanism for
      diaqua[meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]platinum(II)
      sulfate, [Pt(H2O)2(meso-6)]2+SO4(2-), a representative of this series, has been
      investigated and compared with that for cis-[Pt(NH3)2(H2O)2]2+. Reactions were
      followed by atomic absorption, analytical HPLC of Pt-DNA digests, arrest of
      enzymatic DNA synthesis/degradation, ultraviolet and fluorescence
      spectrophotometry. Except for the formation of monofunctional DNA adducts, the
      kinetics of the platinum(II) complexes are comparable. The pseudo-first-order
      rate constant for the attack of DNA by [Pt(H2O)2(meso-6)]2+ follows the
      concentration of DNA in a hyperbolic fashion, which is in contrast to the linear
      dependence for cis-[Pt(NH3)2(H2O)2]2+. The hyperbolic dependence is typical for a
      dissociable DNA/drug complex preceding the coordination reaction. By studying the
      binding of free ligand to DNA, and by correlating ligand structures and
      electrostatic charges with effects on adduct formation, both the phenyl residues
      and the positive charge of the platinum(II) complex are shown to be crucial for
      the stability of the dissociable complex. A non-intercalative mode of binding to
      the DNA backbone is suggested. At the high concentrations of DNA found in cell
      nuclei, the reaction of the dissociable complex can, principally, become rate
      limiting in the attack of DNA and thus reduce the cytotoxic efficiency of a drug.

PMID- 1396664
TI  - Interaction of initiation factors with the cap structure of chimaeric mRNA
      containing the 5'-untranslated regions of Semliki Forest virus RNA is related to
      translational efficiency.
AB  - Chimaeric chloramphenicol acetyltransferase (CAT) mRNA, containing the leader
      sequences of genomic 42S RNA and subgenomic 26S RNA of Semliki Forest virus (SFV)
      were synthesized by in-vitro transcription. These transcripts were translated
      with different efficiencies, as the authentic mRNA in SFV-infected cells.
      Therefore, they can be used as model mRNA species to study the mechanism
      underlying SFV-directed shut off of host protein synthesis. The interaction of
      translation initiation factors with the 5' cap structure was studied. Transcripts
      prepared in vitro using T7 RNA polymerase were capped and methylated
      posttranscriptionally with [32P]-GTP and S-adenosyl-L-methionine to yield cap
      labelled mRNA species. Irradiation with ultraviolet light of 26S CAT and 42S CAT
      transcripts, together with crude rabbit reticulocyte initiation factors, resulted
      in the cap-specific cross-linking of eukaryotic initiation factors (eIF) eIF-4E
      and eIF-4B. The relative binding efficiency of these two factors to the cap
      structure of the various transcripts was, however, markedly different; the cap
      structure present in 26S CAT mRNA interacted efficiently with cap-binding
      proteins, whereas the cap structure of 42S CAT mRNA hardly bound to these
      proteins. Comparable results were obtained under competitive conditions. Data are
      presented that the secondary structure close to the 5' cap structure determines
      the efficiency of recognition of the mRNA by these initiation factors. Using a
      chemical cross-linking assay, it was demonstrated that eIF-4F, and also eIF-4E,
      differentially interacted with the cap structure of the various transcripts. The
      data are discussed with respect to the possible mechanisms involved in SFV
      induced shut off of host cell protein synthesis.

PMID- 1396665
TI  - Splicing of the platelet-derived-growth-factor A-chain mRNA in human malignant
      mesothelioma cell lines and regulation of its expression.
AB  - Platelet-derived-growth-factor (PDGF) A-chain transcripts differing in the
      presence or absence of an alternative exon-derived sequence have been described.
      In some publications, the presence of PDGF A-chain transcripts with this exon-6
      derived sequence was suggested to be tumour specific. However, in this paper it
      was shown by reverse-transcription polymerase-chain-reaction (PCR) analysis that
      both normal mesothelial cells and malignant mesothelioma cell lines predominantly
      express the PDGF A-chain transcript without the exon-6-derived sequence. This
      sequence encodes a cell-retention signal, which means that the PDGF A-chain
      protein is most likely to be secreted by both cell types. In cultured normal
      mesothelial cells, the secreted PDGF A-chain protein might be involved in
      autocrine growth stimulation via PDGF alpha receptors. However, human malignant
      mesothelioma cell lines only possess PDGF beta receptors. If this also holds true
      in vivo, the PDGF A-chain protein produced and secreted by malignant mesothelial
      cells might have a paracrine function. In a previous paper, we described elevated
      expression of the PDGF A-chain transcript in human malignant mesothelioma cell
      lines, compared to normal mesothelial cells. In this paper, the possible reason
      for this elevation was studied. First, alterations at the genomic level were
      considered, but cytogenetic and Southern-blot analysis revealed neither
      consistent chromosomal aberrations, amplification nor structural rearrangement of
      the PDGF A-chain gene in the malignant cells. Possible differences in
      transcription rate of the PDGF A-chain gene, and stability of the transcript
      between normal and malignant cells, were therefore studied. The presence of a
      protein-synthesis inhibitor, cycloheximide, in the culture medium did not
      significantly influence the PDGF A-chain mRNA level in normal mesothelial and
      malignant mesothelioma cell lines. Furthermore, nuclear run-off analysis showed
      that nuclear PDGF A-chain mRNA levels varied in both cell types to the same
      extent as the levels observed in Northern blots. Taken together, this suggests
      that increased transcription is the most probable mechanism for the elevated mRNA
      level of the PDGF A-chain gene in human malignant mesothelioma cell lines.

PMID- 1396666
TI  - In vivo and in vitro modulation of the mRNA-binding activity of iron-regulatory
      factor. Tissue distribution and effects of cell proliferation, iron levels and
      redox state.
AB  - The mRNA-binding protein, iron-regulatory factor (IRF) has a central role in iron
      metabolism. It coordinately increases transferrin-receptor mRNA stability and
      inhibits translation of ferritin and erythroid delta-aminolevulinate synthase
      mRNA by binding to specific mRNA structures, the iron-responsive elements (IRE).
      In gel-retardation assays, IRF had a broad tissue distribution, showing activity
      in cytosolic extracts from 12 mouse organs tested. In all these extracts, IRF
      could be further activated in vitro by 2-mercaptoethanol. In cultured mouse 3T6
      fibroblasts, growth stimulation after low serum arrest increased IRF activity 10
      fold, mainly through activation of existing inactive IRF. No change was observed
      during progression of 3T6 cells through the cell cycle. IRF activation by iron
      chelators has been postulated to result in the reduction of an intramolecular
      sulfhydryl group. In a search for redox conditions that regulate IRE binding of
      IRF, we studied several compounds in vitro or in vivo. Hemin, known to inactivate
      IRF in vivo, showed a similar, reversible effect in vitro, presumably by
      oxidizing IRF. However, this did not appear to be relevant for the mode of IRF
      regulation in vivo. Addition of protoporphyrin IX to intact cells induced IRF
      activity almost to the same extent as desferrioxamine. This effect was inhibited
      by iron salts, indicating that IRF is activated in vivo through depletion of a
      chelatable iron pool. In vitro activation by reductants other than 2
      mercaptoethanol suggested some selectivity in their access to relevant sulfhydryl
      groups, but did not reveal which natural redox-sensitive compound might regulate
      IRF in vivo. However, in cultured cells, inactivation of free IRF by the
      sulfhydryl-specific oxidizing agent diamide was much more rapidly reversed than
      inactivation by iron salts. This indicates the direct involvement of a cellular
      reductant in setting IRF activity and suggests a rate-limiting IRF conformation
      that is reached only in the presence of iron, but not after diamide oxidation.

PMID- 1396667
TI  - The interaction of acetate and formate with cobalt carbonic anhydrase. An NMR
      study.
AB  - The interaction of formate and acetate ions with cobalt-substituted carbonic
      anhydrase (CA) has been investigated through 13C-NMR and one-dimensional and two
      dimensional 1H-NMR spectroscopy. 13C data on formate are consistent with a
      regularly coordinated ligand, as previously proposed for the acetate anion
      [Bertini, I., Luchinat, C. & Scozzafava, A. (1977) J. Chem. Soc. Dalton Trans.,
      1962-1965]. 1H-NOE experiments on both anions give evidence of through-space
      interactions between ligand protons and protein protons. The latter are assigned
      to specific residues in the active cavity through nuclear Overhauser effect
      spectroscopy (NOESY) experiments. The 13C-derived and 1H-derived constrains allow
      reliable docking of these ligands in the active-site cavity. The resulting
      geometries are similar to one another and consistent with five-coordinated
      structures around the metal ion, as previously proposed from electronic
      spectroscopy [Bertini, I., Canti, G., Luchinat, C. & Scozzafava, A. (1978) J. Am.
      Chem. Soc. 100, 4873-4877]. The results are discussed in light of the current
      debate on anion binding to metal ions in carbonic anhydrase [Lindahl, M.,
      Svensson, A. & Liljas, A. (1992) Proteins, in the press]; Bertini, I., Luchinat,
      C., Pierattelli, R. & Vila, A. J. (1992) Inorg. Chem., in the press; Banci, L. &
      Merz, K. (1992) unpublished results] and, in particular, of the proposed long Zn
      O distance found in the recent X-ray results on the formate adduct [Hakanson, K.,
      Carlsson, M., Svensson, A. & Liljas, A. (1992) J. Mol. Biol., in the press].

PMID- 1396668
TI  - Mechanism of the interaction of EcoRII restriction endonuclease with two
      recognition sites. Probing of modified DNA duplexes as activators of the enzyme.
AB  - The efficiency of cleavage of DNA duplexes with single EcoRII recognition sites
      by the EcoRII restriction endonuclease decreases with increasing substrate
      length. DNA duplexes of more than 215 bp are not effectively cleaved by this
      enzyme. Acceleration of the hydrolysis of long single-site substrates by EcoRII
      is observed in the presence of 11-14-bp substrates. The stimulation of hydrolysis
      depends on the length and concentration of the second substrate. To study the
      mechanism of EcoRII endonuclease stimulation, DNA duplexes with base analogs and
      modified internucleotide phosphate groups in the EcoRII site have been
      investigated as activators. These modified duplexes are cleaved by EcoRII enzyme
      with different efficiencies or are not cleaved at all. It has been discovered
      that the resistance of some of them can be overcome by incubation with a
      susceptible canonical substrate. The acceleration of cleavage of long single-site
      substrates depends on the type of modification of the activator. The modified DNA
      duplexes can activate EcoRII catalyzed hydrolysis if they can be cleaved by
      EcoRII themselves or in the presence of the second canonical substrate. It has
      been demonstrated that EcoRII endonuclease interacts in a cooperative way with
      two recognition sites in DNA. The cleavage of one of the recognition sites
      depends on the cleavage of the other. We suggest that the activator is not an
      allosteric effector but acts as a second substrate.

PMID- 1396669
TI  - Degradation of gangliosides by the lysosomal sialidase requires an activator
      protein.
AB  - Lysosomal sialidase, which was formerly believed to degrade only water-soluble
      substrates but not glycolipids, cleaves ganglioside substrates II3NeuNAc-LacCer,
      IV3NeuNAc, II3NeuNAc-GgOse4Cer, IV3 NeuNAc, II3(NeuNAc)2-GgOse4Cer when these are
      dispersed either with an appropriate detergent (taurodeoxycholate) or with the
      sulfatide activator protein, a physiologic lipid solubilizer required for the
      lysosomal hydrolysis of other glycolipids by water-soluble hydrolases. In the
      presence of the activator protein, time and protein dependence were linear within
      wide limits, while the detergent rapidly inactivated the enzyme. The disialo
      group of the b-series gangliosides was only poorly attacked by the enzyme when
      the lipids were dispersed with the activator protein, whereas in the presence of
      the detergent, they were hydrolyzed as fast as terminal sialic acid residues.
      With the appropriate assay method, significant ganglioside sialidase activity
      could be demonstrated in the secondary lysosome fraction of normal skin
      fibroblasts but not of sialidosis fibroblasts. Our results support the notion
      that there is only one lysosomal sialidase, which degrades both the water-soluble
      and the membrane-bound sialyl glycoconjugates.

PMID- 1396670
TI  - Studies on ribonucleoside-diphosphate reductase from Escherichia coli. The
      product dCDP is a competitive inhibitor and functions as a spectroscopic probe
      for the substrate binding site; demonstration by enzyme kinetics and 1H NMR.
AB  - Ribonucleoside-diphosphate reductase (EC 1.17.4.1) from Escherichia coli consists
      of two protein subunits, R1 of 171.5 kDa and R2 of 86.8 kDa, and catalyzes the
      reduction of all four common ribonucleoside diphosphates. In a search for ligands
      that bind weakly to the enzyme active site and may be in fast exchange suitable
      for NMR studies, we have found that the product dCDP is a competitive inhibitor.
      Kinetics with CDP as substrate shows Km = 4.8 x 10(-5) M and dCDP inhibits with
      Ki = 1.6 x 10(-4) M. With an assumed diffusion limited binding rate approximately
      less than 10(9) M-1s-1, the dissociation rate of dCDP would be approximately less
      than 10(5) s-1. In 1H-NMR experiments studying linewidths, i.e. spin-spin
      relaxation, dCDP is indeed demonstrated to be in fast exchange. Enzyme subunit R1
      causes a line broadening of dCDP resonances. Unexpectedly less broadening was
      observed when subunit R2 combined with R1. No paramagnetic interaction from the
      tyrosyl radical of R2 could be detected. It is concluded that dCDP is a promising
      NMR probe for studies of active-site properties of the enzyme.

PMID- 1396671
TI  - Binding of the competitive inhibitor dCDP to ribonucleoside-diphosphate reductase
      from Escherichia coli studied by 1H NMR. Different properties of the large
      protein subunit and the holoenzyme.
AB  - Ribonucleoside-diphosphate reductase (EC 1.17.4.1) from Escherichia coli consists
      of two nonidentical subunits, proteins R1 and R2. The binding of the product dCDP
      to protein R1 and to the holoenzyme R1R2 has been studied by means of 1H-NMR
      spectroscopy. In presence of the effector dTTP at 25 degrees C, dCDP was found to
      be in rapid exchange between the binding sites and the solvent which results in a
      broadening of the dCDP resonances. When both proteins R1 and R2 are present, so
      that the complex R1R2 is formed, a smaller broadening is observed than with
      protein R1 alone. No further linewidth decrease was observed when the [R2]/[R1]
      ratio exceeded 1. The binding constant of dCDP to R1 or R1R2 is the same, Kd =
      0.9 mM. The smaller broadening of the dCDP resonances observed with the complex
      R1R2 as compared with R1 may be explained by the combination of two effects: (a)
      the overall tumbling time of the protein will increase when going from R1 to
      R1R2, which will cause the broadening to increase correspondingly, and (b) a
      twofold decrease of the number of binding sites in rapid exchange, which will
      decrease the broadening by a factor of 0.5. The effect of R2 without iron (apoR2)
      is reduced compared with native R2, probably because of some denatured proteins,
      while a C-terminal peptide from R2 did not cause any narrowing at all.

PMID- 1396672
TI  - Purification and characterization of vanillyl-alcohol oxidase from Penicillium
      simplicissimum. A novel aromatic alcohol oxidase containing covalently bound FAD.
AB  - Vanillyl-alcohol oxidase was purified 32-fold from Penicillium simplicissimum,
      grown on veratryl alcohol as its sole source of carbon and energy. SDS/PAGE of
      the purified enzyme reveals a single fluorescent band of 65 kDa. Gel filtration
      and sedimentation-velocity experiments indicate that the purified enzyme exists
      in solution as an octamer, containing 1 molecule flavin/subunit. The covalently
      bound prosthetic group of the enzyme was identified as 8 alpha-(N3-histidyl)-FAD
      from pH-dependent fluorescence quenching (pKa = 4.85) and no decrease in
      fluorescence upon reduction with sodium borohydride. The enzyme shows a narrow
      substrate specificity, only vanillyl alcohol and 4-hydroxybenzyl alcohol are
      substrates for the enzyme. Cinnamyl alcohol is a strong competitive inhibitor of
      vanillyl-alcohol oxidation. The visible absorption spectrum of the oxidized
      enzyme shows maxima at 354 nm and 439 nm, and shoulders at 370, 417 and 461 nm.
      Under anaerobic conditions, the enzyme is easily reduced by vanillyl alcohol to
      the two-electron reduced form. Upon mixing with air, rapid reoxidation of the
      flavin occurs. Both with dithionite reduction and photoreduction in the presence
      of EDTA and 5-deazaflavin the red semiquinone flavin radical is transiently
      stabilized. Opposite to most flavoprotein oxidases, vanillyl-alcohol oxidase does
      not form a flavin N5-sulfite adduct. Photoreduction of the enzyme in the presence
      of the competitive inhibitor cinnamyl alcohol gives rise to a complete,
      irreversible bleaching of the flavin spectrum.

PMID- 1396674
TI  - Occurrence of alpha 1-2-fucosylation in membrane glycoproteins of Morris hepatoma
      7777 but not in liver. Aberrant type of fucosylation in a malignant tissue.
AB  - A comparative study was undertaken to characterize the linkages of L-fucose in N
      glycans of plasma membrane glycoproteins from Morris hepatoma 7777, host liver
      and kidney cortex, as well as from rat serum. After in-vivo radiolabelling of
      rats with L-[6-3H]fucose, the asparagine-linked carbohydrate chains were released
      from delipidated plasma membrane glycoproteins, as well as from serum
      glycoproteins, by enzymic digestion with peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase from Flavobacterium meningosepticum. They were
      then converted to their corresponding oligosaccharide alditols by reduction with
      sodium borohydride. Two specific alpha-L-fucosidases from almond emulsin and from
      Aspergillus niger, combined with affinity HPLC on immobilized Aleuria aurantia
      lectin were used to study the linkage of L-fucose in the oligosaccharide chains.
      Fucose alpha 1-2 linked to galactose, was present only in the plasma membrane of
      hepatoma 7777 (18% of total L-[3H]fucose in N-glycans), but was not expressed in
      host liver, kidney cortex and serum. None of the investigated sources contained
      an appreciable amount of fucose alpha 1-3/4 linked to N-acetyl-D-glucosamine. All
      the radioactively labelled oligosaccharides from host liver, kidney cortex and
      serum, but only 82% of these oligosaccharides from hepatoma, contained alpha
      fucosyl residues linked at the C6 position of the proximal N-acetyl-D
      glucosamine.

PMID- 1396673
TI  - Mechanistic studies on rhodopsin kinase. Light-dependent phosphorylation of C
      terminal peptides of rhodopsin.
AB  - The phosphorylation of a synthetic peptide, corresponding to the C-terminal 11
      amino acids of bovine rhodopsin (VII, residues 338-348), was studied under
      different conditions. The peptide was only phosphorylated in the presence of
      photoactivated rhodopsin. Using the same protocol, 12 other peptides, mapping in
      the rhodopsin C-terminal, were screened for their effectiveness as substrates for
      rhodopsin kinase. It was found that the peptides became poorer substrates with
      increasing length, and the best substrates comprised the most C-terminal 9-12
      amino acids as opposed to other parts of the C-terminus. It was noted that the
      absence of the two-terminal residues Pro347 and Ala348 impaired peptide
      phosphorylation. The effect of the decay of metarhodopsin II on the
      phosphorylation of rhodopsin and the peptides was determined, and it was found
      that the rhodopsin and peptide phosphorylations decayed with half times of
      approximately 33 min and 28 min, respectively. The sites of phosphorylation on
      the peptides were determined and in all cases the phosphorylation was found to be
      predominantly on serine residues. Only the 11-residue peptide (VII, residues 338
      348) contained significant threonine phosphorylation, which was about 25% that on
      serine residues. Cumulatively, the results suggest that Ser343 is the preferred
      site of phosphorylation in vitro. The reason for the poor substrate effectiveness
      of the larger peptides was examined by competitive experiments in which it was
      shown that a poorly phosphorylated larger peptide successfully inhibited the
      phosphorylation of a 'good' peptide substrate. The studies above support a
      mechanism for rhodopsin kinase that we have termed the 'kinase-activation
      hypothesis'. This requires that the kinase exists in an inactive form and is
      activated only after binding to photoactivated rhodopsin.

PMID- 1396675
TI  - Alkylacyl glycerophosphoinositol in human and bovine erythrocytes. Molecular
      species composition and comparison with glycosyl-inositolphospholipid anchors of
      erythrocyte acetylcholinesterases.
AB  - Glycosyl-inositolphospholipid (glycosyl-PtdIns) anchors of proteins in mammalian
      cells which have been analyzed so far are exclusively of the alkylacyl type.
      However, little is known about the putative precursor of glycosyl-PtdIns, the
      alkylacyl derivative of glycerophosphoinositol (GroPIns), in these cells since it
      is generally believed that cellular GroPIns consists of diacyl-type molecular
      species only. In this report, we describe the isolation and identification of
      alkylacyl GroPIns molecular species in both human and bovine erythrocytes, and
      compare it with the molecular species compositions of the glycosyl-PtdIns anchors
      of human and bovine erythrocyte acetylcholinesterase. Diradyl GroPIns was
      isolated from lipid extracts of ghost membranes and treated with phospholipase C.
      Diradylglycerols of the glycosyl-PtdIns anchors of affinity-purified human and
      bovine erythrocyte acetylcholinesterase were generated by sequential treatment
      with glycoprotein phospholipase D and acidic phosphatase and by PtdIns-specific
      phospholipase C, respectively. Diradylglycerols were subsequently converted into
      benzoate derivatives and separated into diacyl, alkylacyl, and
      alkenylacylglycerol subclasses. The molecular species compositions were
      quantitated and determined by combined HPLC/mass spectrometry. We found that
      human and bovine erythrocyte membrane diradyl GroPIns consist of 1.5-4.8%
      alkylacyl GroPIns. Molecular species analysis showed a heterogeneous species
      composition for both human and bovine erythrocyte alkylacyl GroPIns. Their
      compositions are distinctly different from those of human and bovine erythrocyte
      acetylcholinesterase glycosyl-PtdIns anchors. The number of alkylacyl GroPIns
      molecules/cell is roughly equal with the number of glycosyl-PtdIns-anchored
      proteins in human erythrocytes.

PMID- 1396676
TI  - Precursor of mitochondrial aspartate aminotransferase synthesized in Escherichia
      coli is complexed with heat-shock protein DnaK.
AB  - On expression of the cDNA encoding the precursor of chicken mitochondrial
      aspartate aminotransferase (pmAspAT) in Escherichia coli, the bulk of pmAspAT was
      found to be associated with the 70-kDa heat-shock protein DnaK which is closely
      related to mitochondrial 70-kDa heat-shock protein (HSP70). Purification
      protocols for the DnaK/pmAspAT complex and its individual components were
      elaborated. The complex dissociated on treatment with MgATP or at pH 5.5. Like
      the mature enzyme, pmAspAT is a dimer (2 x 47 kDa) and exhibits about a third of
      its enzyme activity. In the DnaK/pmAspAT complex, one DnaK molecule is bound to
      each subunit of pmAspAT; this tetramer may further aggregate to an octamer. The
      complex is catalytically almost as active as free pmAspAT. It could be
      reconstituted from isolated DnaK and pmAspAT. No complex was formed with mAspAT.
      Apparently, DnaK binds to the solvent-exposed presequence of folded pmAspAT
      without significantly changing the structure and functional properties of its
      mature moiety.

PMID- 1396677
TI  - Regulation of the activity of ribulose-1,5-bisphosphate carboxylase/oxygenase
      through cooperative binding of 6-phosphogluconate to its regulatory sites.
AB  - This study was attempted to elucidate the mechanism of the regulation of the
      turnover number on the catalytic sites by the regulatory sites of spinach
      ribulose-1,5-bisphosphate carboxylase/oxygenase [Rbu(1,5)P2CO]. To this end, we
      analyzed the effects of the binding of 6-phosphogluconate (6-P-Gln) to the
      regulatory sites of the enzyme on the progress in the subsequent catalysis
      assayed with 0.5 mM ribulose 1,5-bisphosphate [Rbu(1,5)P2]. This concentration of
      Rbu(1,5)P2 hardly binds to the regulatory sites but competes with 6-P-Gln for the
      catalytic sites. An equilibrium binding assay showed that Rbu(1,5)P2CO bound 8
      mol 6-P-Gln/mol enzyme in addition to the catalytic sites. The binding to the
      eight regulatory sites was positively cooperative. The biphasic reaction course,
      inherent in the carboxylase reaction of plant Rbu(1,5)P2CO and composed of a
      burst for an initial few minutes and a subsequent linear phase, became faint with
      increasing binding of 6-P-Gln to the sites. The change of the reaction progress
      from the biphasic to linear course was ascribed to the suppression of the
      functioning form of the enzyme from the high-activity to low-activity form and to
      the increased turnover number on the catalytic sites though the binding of 6-P
      Gln to the regulatory sites.

PMID- 1396678
TI  - Characterization of the cytochrome P-450IID subfamily in bovine liver. Nucleotide
      sequences and microheterogeneity.
AB  - To elucidate the molecular mechanisms underlying drug detoxification, the
      structures of the members of the microsomal cytochrome P-450IID subfamily were
      analyzed by isolating, mapping and sequencing cytochrome P-450IID (CYP2D) cDNA
      clones from bovine liver. The screening was performed under nonstringent
      conditions so that most of the P-450IID subfamily members could be obtained. 114
      of the 147 positive clones were classified into four groups on the basis of their
      restriction-enzyme maps. The maps of the four groups were highly similar,
      however, the clones of one group contained an insertion of approximately 500 bp
      in the coding region. Analysis of partial nucleotide sequences of several
      representative clones from each group showed that the bovine P-450IID subfamily
      in liver consisted of several, not many, highly similar members, differing by
      less than 7% in their nucleotide sequences. The location of the insertion found
      in the minor group corresponded to intron 7 and the GT/AG rule was found at the
      exon/intron boundary, suggesting that intron 7 was retained in this group. The
      complete nucleotide sequences of two clones from the major group were examined to
      determine the structures of the P-450IID subfamily in bovine liver. A full-length
      cDNA clone (1615 bp) and a partial cDNA clone (1538 bp) contained open reading
      frames encoding 500 and 487 amino acid residues, respectively. The partial clone
      lacked the nucleotide sequence corresponding to the first 13 N-terminal amino
      acid residues. The deduced amino acid sequences of the two clones were 98%
      similar, and 80% and 68% similar to those from human CYP2D6 and rat CYP2D1,
      respectively. Comparisons of the amino acid sequences of the P-450IID subfamily
      members showed the highly conserved C-terminal region of their molecules and the
      high similarity between the members in one species, especially in cattle and man.

PMID- 1396679
TI  - Transient activation of hepatic glycogenolysis by thrombin in perfused rat
      livers.
AB  - Thrombin, a peptide with native protease activity, caused a rapid (less than 1
      min) increase in glycogenolysis of about 30%, assessed from rates of production
      of glucose+lactate+pyruvate, and in oxygen uptake in perfused rat liver. These
      increases were followed by a rapid return to basal values within 5 min. The
      effect of thrombin on glycogenolysis was dose-dependent and was maximal at
      perfusate concentrations around 1 U/ml. Interestingly, the effect of thrombin on
      glycogenolysis could be elicited only once in any given liver. The activation of
      glycogenolysis by thrombin was diminished nearly 50% by prior infusion of the
      protease inhibitor, diisopropyl fluorophosphate (10 microM), and over 90% when
      thrombin was treated with diisopropyl fluorophosphate prior to infusion. The
      stimulation of glycogenolysis by thrombin could be detected in isolated
      hepatocytes or in livers stored for 24 h in cold Euro-Collins solution, a
      treatment which destroys endothelial cells. Further, thrombin stimulated
      production of prostaglandin D2 from arachidonic acid in cultured hepatic
      endothelial but not Kupffer cells. The effect of thrombin on carbohydrate output
      was also blocked by a phospholipase A2 inhibitor (quinacrine, 50 microM) and by
      an inhibitor of the cyclooxygenase (indomethacin, 20 microM), suggesting the
      involvement of cyclooxygenase in the mechanism of action of thrombin. In support
      of this idea, the transient kinetics of stimulation of glycogenolysis by thrombin
      and arachidonic acid was nearly identical to release of thromboxane B2 (80-420
      pg/ml) and prostaglandin D2 (300-900 pg/ml) from the perfused liver. Further, a
      second addition of thrombin failed to increase thromboxane and prostaglandin D2
      release as well as carbohydrate production, supporting a causal link between
      these phenomena. Taken together, these data support the hypothesis that thrombin
      interacts with receptors in the liver, possibly on endothelial cells, leading to
      activation of phospholipase A2 and subsequent transient production of
      prostaglandins and thromboxanes. These mediators subsequently interact with
      receptors on parenchymal cells, leading to a transient stimulation of
      glycogenolysis.

PMID- 1396680
TI  - Affinity purification of cytochrome c reductase from potato mitochondria.
AB  - Ubiquinol-cytochrome-c oxidoreductase has been isolated from potato (Solanum
      tuberosum L.) mitochondria by cytochrome-c affinity chromatography and gel
      filtration chromatography. The procedure, which up to now only proved applicable
      to Neurospora, yields a highly pure and active protein complex in monodisperse
      state. The molecular mass of the purified complex is about 650 kDa, indicating
      that potato cytochrome c reductase occurs as a dimer. Upon reconstitution into
      phospholipid membranes, the dimeric enzyme catalyzes electron transfer from a
      synthetic ubiquinol to equine cytochrome c with a turnover number of 50 s-1. The
      activity is inhibited by antimycin A and myxothiazol. A myxothiazol-insensitive
      and antimycin-sensitive transhydrogenation reaction, with a turnover number of 16
      s-1, can be demonstrated as well. The protein complex consists of ten subunits,
      most of which have molecular masses similar to those of the nine-subunit fungal
      enzyme. Individual subunits were identified immunologically and spectral
      properties of b and c cytochromes were monitored. Interestingly, an additional
      'core' polypeptide which is not present in other cytochrome bc1 complexes forms
      part of the enzyme from potato. Antibodies raised against individual polypeptides
      reveal that the core proteins are clearly immuno-distinguishable. The additional
      subunit may perform a specific function and contribute to the high molecular mass
      which exceeds those reported for other cytochrome-c-reductase dimers.

PMID- 1396682
TI  - Induction of H1(0)-gene expression in B16 murine melanoma cells.
AB  - Histone H1(0) accumulation is associated with the terminal stage of
      differentiation. Unlike other H1 histones, it is able to accumulate in the
      absence of DNA synthesis, however the transcription of its gene is cell-cycle
      dependent. The regulation of H1(0)-gene expression has been studied during the
      induced differentiation of B16 cells and during reversion of the process, which
      may be achieved when induced cells are released into an inducing-agent-free
      medium. During the earlier period of induced differentiation, H1(0) mRNA showed
      over-expression when the cells were still proliferating. Then the amount of H1(0)
      mRNA decreased as the cells became arrested in G0-G1. H1(0) mRNA half-life
      measurements and run-on experiments demonstrated that such modulation of the
      amount of mRNA originated from a transcriptional control of H1(0)-gene
      expression. When induced cells reverted to a proliferative undifferentiated
      state, H1(0) mRNA decreased very rapidly, indicating that an active process was
      involved in this decay. This behavior differed from that observed in rat liver
      hepatocytes allowed to proliferate and de-differentiate after partial
      hepatectomy, or in murine erythroleukemia cells when the inducing agent was
      removed from the culture.

PMID- 1396681
TI  - Characterization of the chicken alpha 1(VI) collagen promoter.
AB  - The promoter of the chicken alpha 1(VI) collagen gene resembles the 5'-flanking
      regions of many housekeeping genes. It lacks a canonical TATAA box but contains
      potential binding sites for transcription factors AP1 and SP1. The promoter
      region has a relatively high GC content and forms a typical CpG island. In
      accordance with the absence of a TATAA element, the gene contains multiple
      transcription-initiation sites distributed over 80 bp genomic DNA. A 621-bp
      fragment derived from the 5' end of the alpha 1(VI) collagen gene is able to
      direct transcription of a heterologous reporter gene in transient-expression
      assays. Other DNA fragments that are either shorter or longer than the 621-bp
      fragment show markedly reduced promoter activity. Thus, the basic promoter
      element of the alpha 1(VI) collagen gene must reside within this 621-bp fragment.

PMID- 1396683
TI  - Stoichiometry of interaction between interferon gamma and its receptor.
AB  - The biological response of interferon gamma is mediated by binding to a specific
      cell-surface receptor. We investigated the stoichiometry of this binding using
      soluble receptors produced in prokaryotic and eukaryotic expression systems
      comprising the extracellular ligand-binding domain of the native protein. The
      ligand-receptor complexes were analyzed by cross-linking, chromatography,
      analytical ultracentrifugation and laser-light scattering. Cross-linking and
      chromatography showed that the stoichiometry of the interaction between ligand
      and receptor depends on the molar ratios of the two components mixed. All
      approaches confirmed that mixtures of ligand-receptor complexes are formed with
      one interferon-gamma dimer bound by one or two receptors. The soluble receptor
      produced in Escherichia coli mainly showed a ligand/receptor stoichiometry of
      1:1, while the receptors produced in eukaryotic cells showed a stoichiometry of
      binding of 1:2. This apparent discrepancy is most likely due to the
      conformational heterogeneity of the Escherichia-coli-derived protein.

PMID- 1396684
TI  - Biochemical properties of the proteasome from Thermoplasma acidophilum.
AB  - We have purified proteasomes to apparent homogeneity from the archaebacterium
      Thermoplasma acidophilum. This proteinase has a molecular mass of about 650 kDa
      and an isoelectric point of 5.6. The proteasome hydrolyses peptide substrates
      containing an aromatic residue adjacent to the reporter group, as well as
      [14C]methylated casein optimally at pH 8.5 and 90 degrees C. The enzyme activity
      is enhanced severalfold by Mg2+ and Ca2+ at 25-500 mM. This increase in activity
      results primarily from a change in Km. The serine-proteinase inhibitors
      diisopropylfluorophosphate and 3,4-dichloroisocoumarin irreversibly inhibit the
      enzyme, obviously by modification of both the alpha and beta subunits in the
      proteasome. The inhibition of proteasomal activity by the peptidylchloromethanes,
      Cbz-Leu-Leu-CH2Cl and Cbz-Ala-Ala-Phe-CH2Cl (Cbz, benzyloxycarbonyl), is
      reversible and predominantly of a competitive type. The enzyme is not activated
      by any of the compounds that typically stimulate the activities of the eukaryotic
      proteasome.

PMID- 1396685
TI  - Cloning and overexpression of Lactobacillus helveticus D-lactate dehydrogenase
      gene in Escherichia coli.
AB  - NAD(+)-dependent D-lactate dehydrogenase from Lactobacillus helveticus was
      purified to apparent homogeneity, and the sequence of the first 36 amino acid
      residues determined. Using forward and reverse oligonucleotide primers, based on
      the N-terminal sequence and amino acid residues 220-215 of the Lactobacillus
      bulgaricus enzyme [Kochhar, S., Hunziker, P. E., Leong-Morgenthaler, P. &
      Hottinger, H. (1992) J. Biol. Chem. 267, 8499-8513], a 0.6-kbp DNA fragment was
      amplified from L. helveticus genomic DNA by the polymerase chain reaction. This
      amplified DNA fragment was used as a probe to identify two recombinant clones
      containing the D-lactate dehydrogenase gene. Both plasmids overexpressed D
      lactate dehydrogenase (greater than 60% total soluble cell protein) and were
      stable in Escherichia coli, compared to plasmids carrying the L. bulgaricus and
      Lactobacillus plantarum genes. The entire nucleotide sequence of the L.
      helveticus D-lactate dehydrogenase gene was determined. The deduced amino acid
      sequence indicated a polypeptide consisting of 336 amino acid residues, which
      showed significant amino acid sequence similarity to the recently identified
      family of D-2-hydroxy-acid dehydrogenases [Kochhar, S., Hunziker, P. E., Leong
      Morgenthaler, P. & Hottinger, H. (1992) Biochem. Biophys. Res. Commun. 184, 60
      66]. The physicochemical and catalytic properties of recombinant D-lactate
      dehydrogenase were identical to those of the wild-type enzyme, e.g. alpha 2
      dimeric subunit structure, isoelectric pH, Km and Kcat for pyruvate and other 2
      oxo-acid substrates. The kinetic profiles of 2-oxo-acid substrates showed some
      marked differences from that of L-lactate dehydrogenase, suggesting different
      mechanisms for substrate binding and specificity.

PMID- 1396686
TI  - Production of Fenton's reagent by cellobiose oxidase from cellulolytic cultures
      of Phanerochaete chrysosporium.
AB  - The reduction of dioxygen by cellobiose oxidase leads to accumulation of H2O2,
      with either cellobiose or microcrystalline cellulose as electron donor.
      Cellobiose oxidase will also reduce many Fe(III) complexes, including Fe(III)
      acetate. Many Fe(II) complexes react with H2O2 to produce hydroxyl radicals or a
      similarly reactive species in the Fenton reaction as shown: H2O2 + Fe2+----HO. +
      HO- + Fe3+. The hydroxylation of salicylic acid to 2,3-dihydroxybenzoic acid and
      2,5-dihydroxybenzoic acid is a standard test for hydroxyl radicals. Hydroxylation
      was observed in acetate buffer (pH 4.0), both with Fe(II) plus H2O2 and with
      cellobiose oxidase plus cellobiose, O2 and Fe(III). The hydroxylation was
      suppressed by addition of catalase or the absence of iron [Fe(II) or Fe(III) as
      appropriate]. Another test for hydroxyl radicals is the conversion of deoxyribose
      to malondialdehyde; this gave positive results under similar conditions. Further
      experiments used an O2 electrode. Addition of H2O2 to Fe(II) acetate (pH 4.0) or
      Fe(II) phosphate (pH 2.8) in the absence of enzyme led to a pulse of O2 uptake,
      as expected from production of hydroxyl radicals as shown: RH+HO.----R. + H2O; R.
      + O2----RO2.----products. With phosphate (pH 2.8) or 10 mM acetate (pH 4.0), the
      O2 uptake pulse was increased by Avicel, suggesting that the Avicel was being
      damaged. Oxygen uptake was monitored for mixtures of Avicel (5 g.1-1), cellobiose
      oxidase, O2 and Fe(III) (30 microM). An addition of catalase after 20-30 min
      indicated very little accumulation of H2O2, but caused a 70% inhibition of the O2
      uptake rate. This was observed with either phosphate (pH 2.8) or 10 mM acetate
      (pH 4.0) as buffer, and is further evidence that oxidative damage had been taking
      place, until the Fenton reaction was suppressed by catalase. A separate binding
      study established that with 10 mM acetate as buffer, almost all (98%) of the
      Fe(III) would have been bound to the Avicel. In the presence of Fe(III),
      cellobiose oxidase could provide a biological method for disrupting the
      crystalline structure of cellulose.

PMID- 1396687
TI  - Molecular cloning of the antibacterial protein of the giant African snail,
      Achatina fulica Ferussac.
AB  - An expression cDNA library was constructed with poly(A)-rich RNA extracted from
      the collar of the giant African snail, Achatina fulica Ferussac. A 1.9-kbp cDNA
      clone encoding a precursor of antibacterial glycoprotein of the snail, achacin,
      was isolated from the cDNA expression library. The cDNA sequence contains an open
      reading frame with 1593-nucleotide residues. The deduced amino acid sequence of
      this achacin precursor starts with a 29-residue leader peptide followed by a 502
      residue mature peptide (56 kDa) with four possible N-glycosylation sites, Asn-Xaa
      Ser or Asn-Xaa-Thr. The Northern-blot analysis proved that the achacin precursor
      was specifically expressed in the tissue of snail collar and processed to mature
      achacin. cDNA inserts encoding achacin precursor were subcloned into expression
      plasmids. Three kinds of expressed polypeptides were cross-reacted with rabbit
      antiserum raised against achacin. The largest polypeptide (M(r) 63,000) should be
      the achacin precursor.

PMID- 1396688
TI  - Purification, characterization and gene structure of (1-->3)-beta-glucanase
      isoenzyme GIII from barley (Hordeum vulgare).
AB  - A new member of the barley (1-->3)-beta-glucan glucanohydrolase family of enzymes
      has been purified from extracts of germinated grain and young seedlings by
      fractional precipitation with ammonium sulphate, ion-exchange chromatography,
      chromatofocussing and gel-filtration chromatography. The enzyme, which has been
      designated (1-->3)-beta-glucanase isoenzyme GIII, is a basic protein with an
      apparent molecular mass of 32 000 Da. Oligosaccharide products released by the
      enzyme during hydrolysis of the (1-->3)-beta-glucan, laminarin, indicate that the
      enzyme is an endohydrolase. A 2349-bp fragment of barley genomic DNA has been
      isolated and identified as the gene encoding the (1-->3)-beta-glucanase isoenzyme
      GIII. The open reading frame encoding the isoenzyme is interrupted by a single
      intron of 180 bp that splits a codon in the putative signal-peptide region.
      Northern-blot analyses with gene-specific probes indicate that the (1-->3)-beta
      glucanase isoenzyme GIII mRNA accumulates in developing leaves; no mRNA
      transcripts were detected in the aleurone or scutellum of germinated grain, or in
      mature vegetative tissues. Although plant (1-->3)-beta-glucanases are generally
      classified as 'pathogenesis-related' proteins, the physiological function of the
      barley (1-->3)-beta-glucanase isoenzyme GIII is unclear.

PMID- 1396689
TI  - Endocytosis of thyroglobulin is not mediated by mannose-6-phosphate receptors in
      thyrocytes. Evidence for low-affinity-binding sites operating in the uptake of
      thyroglobulin.
AB  - Thyroglobulin, the major secretory product of thyrocytes, is the macromolecular
      precursor of thyroid hormones. After its synthesis, thyroglobulin follows a
      complex secretion, storage and recapture pathway to lysosomes. Porcine
      thyroglobulin was shown to carry the mannose 6-phosphate-(Man6P)-recognition
      marker on its N-linked glycans. Since the cation-independent Man6P receptor could
      also be found on the apical plasma membrane of porcine thyrocytes, we examined
      the significance of the Man6P signal for the transport of thyroglobulin. Here, we
      present data implying that Man6P receptors are not relevant for endocytosis of
      thyroglobulin in thyrocytes. Instead, we provide evidence for the existence of
      specific, low-affinity-binding sites for thyroglobulin on the apical plasma
      membrane of thyrocytes responsible for endocytosis of thyroglobulin. Binding
      studies with intact, polar-organized porcine thyrocytes grown on collagen-coated
      filters revealed cooperative and saturable binding of thyroglobulin to the apical
      plasma-membrane domain at relatively high concentrations of thyroglobulin (20
      microM). These observations show that low-affinity interactions between
      thyroglobulin and the apical plasma membrane play a key role in endocytosis of
      thyroglobulin and hormone formation in the thyroid. The data in this publication
      have been published as an abstract [Lemansky, P. and Herzog, V. (1991) J. Cell
      Biol. 115, 261a].

PMID- 1396690
TI  - Gene cloning and characterization of a novel extracellular ribonuclease of
      Bacillus subtilis.
AB  - An extracellular nuclease gene of Bacillus subtilis was cloned in the same
      organism by detecting the amplified enzyme activity, which was secreted from the
      transformant cells on an RNA-containing agar medium. An open reading frame
      encoding 289 amino acids was identified within the cloned fragment. The
      transcriptional initiation site was determined by nuclease S1 mapping and the
      promoter region showed similarity to the conserved recognition sequences for the
      E sigma A and/or E sigma E RNA polymerases. The production of the nuclease by the
      B. subtilis transformants greatly depends on the liquid medium used. SDS/PAGE
      analysis of the purified enzyme showed two adjoining bands of molecular mass
      about 32 kDa, and the NH2-terminal amino acid sequence analysis suggested that
      the NH2-terminal portion of the nuclease was subjected to a limited proteolysis
      after or during secretion. The nuclease was uniquely characterized as a Mg(2+)
      activated ribonuclease which hydrolyzes RNA apparently nonspecifically into
      oligonucleotides with 5'-terminal phosphate. The deduced amino acid sequence of
      this enzyme shows no obvious similarity with other nuclease sequences.

PMID- 1396691
TI  - Isolation, sequence analysis and characterization of cDNA clones coding for the C
      chain of mouse C1q. Sequence similarity of complement subcomponent C1q, collagen
      type VIII and type X and precerebellin.
AB  - A mouse macrophage lambda gt11 cDNA library was screened using a genomic DNA
      clone coding for the C-chain gene of human C1q. Approximately 600,000 recombinant
      phage plaques were hybridized with peroxidase-labeled human C-chain probe and
      detected by enhanced chemiluminescence. Five positive clones were obtained. The
      size of the full-length cDNA is 1019 bp. The sequence identity of the nucleotide
      sequence with human C1q C chain is 79%, the identity of the deduced amino acid
      sequences is 73%. The mouse C1q C chain exhibits the same structural features as
      the human C chain, e.g. conservation of the cysteine residues. Like the mouse A
      chain, the mouse C chain has an RGD sequence that may be recognized by receptors
      of the integrin family. No RGD sequences have been found in any of the human C1q
      chains. The size of the C-chain mRNA (1.2 kb) and its tissue distribution
      (macrophages being the cell type with the highest mRNA concentration) are
      identical to the mRNA of the mouse A and B chains. Alignment of human and mouse
      C1q A, B and C chains exhibits two blocks of highly conserved residues within the
      C-terminal globular regions. Three other proteins, collagen type VIII and type X
      and precerebellin share this similarity with C1q, indicating the structural and
      probably functional importance of these regions within the non-collagenous
      domains of the molecules.

PMID- 1396692
TI  - Cloning and nucleotide sequences of genes relevant for biosynthesis of poly(3
      hydroxybutyric acid) in Chromatium vinosum strain D.
AB  - From a genomic library of Chromatium vinosum strain D in lambda L47, a 16.5-kbp
      EcoRI-restriction fragment was identified by hybridization with a DNA fragment
      harboring the operon for Alcaligenes eutrophus poly(3-hydroxyalkanoate) (PHA)
      synthesis. This fragment and subfragments thereof restored the ability to
      synthesize and accumulate PHA in PHA-negative mutants of A. eutrophus. A region
      of 6977 bp was sequenced; seven open reading frames (ORFs) were identified which
      probably represent coding regions; six of these are most probably relevant for
      PHA biosynthesis in C. vinosum. The structural genes for biosynthetic acetyl-CoA
      acyltransferase (beta-ketothiolase; phbACv, 1188 bp) and NADH-dependent
      acetoacetyl-CoA reductase (phbBCv, 741 bp) were separated by ORF4 (462 bp) and
      ORF5 (369 bp). Downstream of phbBCv ORF7 (471 pb) was identified which was not
      completed at the 3' terminus. The functions of ORF4, ORF5, and ORF7 are not
      known. The amino acid sequences of beta-ketothiolase and acetoacetyl-CoA
      reductase deduced from phbACv and phbBCv, exhibited a similarity of 68.2% and
      56.4% identical amino acids, respectively, to the corresponding enzymes of A.
      eutrophus. Antilinear to and upstream of the genes mentioned above, two genes
      were identified which were transcribed from a sigma 70-dependent promoter. This
      promoter overlapped with and was divergent to the phbACv promoter; the
      transcriptional start sites were mapped by S1 nuclease protection assays. These
      genes were ORF2 (1074 bp), whose function is not known but whose presence in
      Escherichia coli is essential for expression of PHA synthase activity, and the
      structural gene for a PHA synthase of low M(r) (phbCCv, 1068 bp). The gene
      products of ORF2 and phbCCv, with M(r) of 40,525 and 39,730, respectively, were
      expressed in E. coli applying the T7 RNA polymerase/promoter system. Although the
      amino acid sequence of PHA synthase deduced from phbCCv exhibited only 24.7%
      overall similarity with the PHA synthase of A. eutrophus, highly conserved
      regions were identified.

PMID- 1396693
TI  - Cloning and molecular analysis of the poly(3-hydroxyalkanoic acid) gene locus of
      Pseudomonas aeruginosa PAO1.
AB  - From genomic libraries, the polyhydroxyalkanoate gene locus of Pseudomonas
      aeruginosa PAO1 was cloned and characterised at the molecular level. Two genes
      coding for polyhydroxyalkanoate synthases, phaC1Pa and phaC2Pa, a
      polyhydroxyalkanoate depolymerase gene, phaDPa, and four adjacent open reading
      frames (ORF1, ORF2, ORF3 and ORF4) were identified from the nucleotide sequence.
      Two transcriptional start sites, which were preceded by sequences resembling the
      Escherichia coli consensus sequences for sigma 54 and sigma 70 promoters, were
      identified experimentally upstream of phaC1Pa, which was shown by Northern blot
      analysis to constitute an operon together with phaDPa. A third putative promoter
      resembling the E. coli consensus sequence for sigma 70-dependent promoters was
      proposed upstream of phaC2Pa, which is in a bicistronic operon with ORF3.
      Investigations of rpoN-negative mutants of related strains revealed that
      polyhydroxyalkanoate accumulation from gluconate required an intact rpoN locus in
      P. aeruginosa. Complementation experiments revealed multiple evidence that either
      polyhydroxyalkanoate synthase is involved in polyhydroylkanoate accumulation from
      gluconate as well as from octanoate. The P. aeruginosa PAO1 polyhydroxyalkanoate
      gene locus was expressed in the polyhydroxyalkanoate-negative mutant Alcaligenes
      eutrophus PHB-4 and in the poly(3-hydroxybutyrate)-accumulating strain P.
      oleovorans DSM1045. It conferred on the latter the ability to synthesize and
      accumulate polyhydroxyalkanoates consisting of medium-chain-length 3
      hydroxyalkanoic acids from unrelated substrates in addition to poly(3
      hydroxybutyrate). The sequence of the putative translational product of ORF1 was
      similar to those of the leukotoxin repressor of Pasteurella haemolytica and to
      the ORF9 product of Azotobacter vinelandii, and that of ORF4 was similar to the
      algP product of P. aeruginosa and to eukaryotic histone H1 proteins. The proteins
      of ORF2 and ORF3 appear to be previously unidentified.

PMID- 1396694
TI  - Efficiency of the 5'-terminal sequence (omega) of tobacco mosaic virus RNA for
      the initiation of eukaryotic gene translation in Escherichia coli.
AB  - Recent studies have demonstrated that the 5' leader (omega sequence) of tobacco
      mosaic virus RNA has a certain enhancing capacity for translation of mRNA in both
      prokaryotes and eukaryotes. In order to estimate the efficiency of omega to
      initiate translation of mRNA in Escherichia coli, in comparison to the Shine
      Dalgarno (S/D) sequence, we have inserted eight different eukaryotic genes into
      two types of E. coli expression vectors containing one constitutive promoter (P1)
      but different translation-initiation sites (S/D or omega delta 3 sequence,
      respectively). The efficiency of transcription and translation in vivo was
      evaluated for these vectors by measuring the yield of protein and both the level
      and stability of mRNA. We report that substitution of omega delta 3 for S/D
      decreases the yield of expressed protein 4-1900-fold and the content of gene
      specific mRNA is decreased by about sevenfold. However, in comparison with the
      S/D sequence, the level of protein expressed under the translational control of
      omega delta 3 is less sensitive to changes in the 5' coding region. We also
      report that the omega sequence contains a region of 10-12 nucleotides
      complementary to the small ribosomal subunit RNA (rRNA) of E. coli, Eikenella
      corrodens and Xenopus laevis, and to the rRNA of the (small ribosomal) subunit of
      Oryza sativa.

PMID- 1396695
TI  - A gene expressed preferentially in the globular stage of somatic embryogenesis
      encodes elongation-factor 1 alpha in carrot.
AB  - We have isolated cDNA of genes that are preferentially expressed during somatic
      embryogenesis of carrot (Daucus carota L.) by differential screening of globular
      embryos and cells that are dividing in an unorganized manner. As a result of
      Northern-blot analysis, one of the genes identified in this way, which we refer
      to as CEM1, was found to be expressed at high levels in somatic embryos at the
      globular and heart-shaped stages. In-situ hybridization using globular embryos
      revealed that the mRNA transcribed from CEM1 was located preferentially in the
      spherical region of the globular embryo. A homology search using the amino acid
      sequence deduced from the nucleotide sequence of the CEM1 cDNA revealed that CEM1
      encodes the eukaryotic translational elongation-factor 1 alpha.

PMID- 1396696
TI  - The structure of the mammalian antibacterial peptide cecropin P1 in solution,
      determined by proton-NMR.
AB  - Cecropins are peptides with antibacterial activity originally found in insects.
      Recently a cecropin-type peptide was isolated from pig intestine. This peptide,
      porcine cecropin P1, which has 31 amino acid residues and is not amidated in the
      C-terminus, has been synthesized, purified, and investigated by CD and two
      dimensional 1H-NMR at pH 5.0 in aqueous solution with 30% (by vol.) 1,1,1,3,3,3
      hexafluoro-2-propanol. All proton resonances have been assigned except for the N
      terminal serine. Using constraints derived from NOE connectivities and 3JNH alpha
      coupling constants, three-dimensional structures have been calculated by means of
      a distance-geometry program. Some of these structures have been refined by energy
      minimization and restrained molecular dynamics. The structures reveal an alpha
      helix of approximately seven turns along nearly the full length of the peptide.
      The central part of the helix is very well defined by the NMR constraints. Also
      the chemical shifts of the alpha protons and the results of CD measurements are
      in accord with this structure, which is different from the helix-hinge-helix
      structure earlier found in cecropin A and related peptides. In the alpha-helix of
      cecropin P1 there is a long amphipathic section, of 4-5 turns, and a short
      hydrophobic section of one to two turns, with an intervening Glu-Gly sequence,
      which is a potential bend-forming section. The helix can easily span a lipid
      membrane.

PMID- 1396697
TI  - The binding of mutant actins to profilin, ATP and DNase I.
AB  - Twenty-five mutations were created in the Drosophila melanogaster Act88F actin
      gene by in vitro mutagenesis and the mutant actins expressed in vitro. The
      affinity of the mutant actins for ATP, profilin and DNase I was determined. They
      were also tested for conformational changes by non-denaturing gel
      electrophoresis. Mutations at positions 364 (highly conserved) and 366
      (invariant) caused changes in conformation, reduced ATP binding and increased
      profilin binding. At position 362 (invariant) only the conservative change from
      tyrosine to phenylalanine had no effect; other changes at this position affected
      conformation, ATP and profilin binding. Although only glycine or serine occur
      naturally at position 368, changes to threonine or glutamine had no effect on the
      actin. The mutant in which Asp363 was replaced by His and that in which Glu364
      was replaced by Lys decreased DNase I binding, yet neither amino acid occurs in
      the DNase I binding site. Likewise several mutations affect ATP and profilin
      binding but are distant from the binding sites. We conclude that, although actin
      has a highly conserved amino acid sequence, individual amino acids can have
      variable tolerance for substitutions. Also amino acid changes can exert
      significant effects on the binding of ligands to distant parts of the actin
      structure.

PMID- 1396698
TI  - NMR study of the solution conformation of actinomycin D.
AB  - The solution conformation of actinomycin D, the Gram-positive antibiotic and DNA
      binding drug, has been determined by 1H-NMR in deuterated dimethyl sulfoxide. The
      structure determination is based on the experimental data set of NOE restraints.
      Four structures were obtained from the distance geometry and restrained molecular
      dynamics calculation. The resultant structures satisfy the experimental
      restraints very well. These structures are found to be compatible with the X-ray
      crystal structures.

PMID- 1396699
TI  - Characterization of a Xenopus laevis skin peptidylglycine alpha-hydroxylating
      monooxygenase expressed in insect-cell culture.
AB  - The C-terminal amide structure of peptide hormones and neurotransmitters is
      synthesized via a two-step reaction catalyzed by peptidylglycine alpha
      hydroxylating monooxygenase (PHM) and peptidylhydroxyglycine N-C lyase. A Xenopus
      laevis PHM expressed in insect-cell culture by the baculovirus-expression-vector
      system was purified to homogeneity and characterized. Using a newly established
      assay system for PHM, the kinetic features of this enzyme were investigated. As
      expected, the enzyme required copper ions, L-ascorbate and molecular oxygen for
      turnover. Salts like KI and KCl, and catalase stabilized the enzyme in the
      presence of L-ascorbate. The optimum pH value for the enzyme reaction was around
      six when Mes buffer was used and around seven when phosphate buffer was used
      under the same assay condition. Below pH 6, acetate, iodide and chloride ions
      activated the reaction. The kinetic analysis is consistent with a ping-pong
      mechanism with respect to peptide and L-ascorbate, and the peptide showed
      substrate inhibition. The substrate specificity of the enzyme at the penultimate
      position was examined by competitive assay using tripeptides with glycine at the
      C-termini and the inhibitory potency of these peptides in descending order was
      methionine > aromatic > non-polar amino acids.

PMID- 1396700
TI  - Effects of nutrients and hormones on gene expression of ATP citrate-lyase in rat
      liver.
AB  - Northern-blot analyses demonstrated a strong gene expression of ATp citrate-lyase
      in liver and adipose tissue of rat and a weak expression in brain, heart, small
      intestine and muscle. After refeeding a carbohydrate/protein diet to fasted rats,
      the transcriptional rate had already increased within 2 h, the mRNA concentration
      reached a maximal level of approximately 30-fold increased in 16 h, and the
      enzyme induction increased sixfold in 48 h. By feeding only carbohydrate without
      protein, the transcriptional rate was increased threefold, and the mRNA
      concentration and enzyme induction comparably, to the levels in the
      carbohydrate/protein diet. It appears that protein feeding is not necessary to
      induce ATP citrate-lyase. In diabetic rats fed on a glucose diet, the
      transcriptional rate, mRNA concentration and enzyme level were very low in
      comparison with the normal. By fructose feeding, however, the transcriptional
      rate was more greatly increased and the mRNA concentration increased comparably
      to the levels reached by insulin treatment, while the enzyme induction was not so
      increased. Thus, it is suggested that insulin is important in regulated
      translation in addition to transcription. However, triiodothyronine treatment did
      not have much effect on the gene expression. As a result of the present
      experiment, it is noted that ATP citrate-lyase-gene expression was greatly
      dependent on carbohydrate.

PMID- 1396701
TI  - Short-chain dehydrogenases. Proteolysis and chemical modification of prokaryotic
      3 alpha/20 beta-hydroxysteroid, insect alcohol and human 15-hydroxyprostaglandin
      dehydrogenases.
AB  - Prokaryotic 3 alpha/20 beta-hydroxysteroid dehydrogenase exhibits one segment
      sensitive to proteolysis with Glu-C protease and trypsin (cleaving after Glu192
      and Arg196, respectively). Cleavage is associated with dehydrogenase
      inactivation; the presence of NADH offers almost complete protection and
      substrate (cortisone) gives some protection. Distantly related insect alcohol
      dehydrogenase is more resistant to proteolysis, but cleavage in a corresponding
      segment is detectable with Asp-N protease (cleaving before Asp198), while a
      second site (at Glu243) is sensitive to cleavage with both Glu-C and Asp-N
      proteases. Combined, the results suggest the presence of limited regions
      especially sensitive to proteolysis and the possibility of some association
      between the enzyme active site and the sensitive site(s). Modification of the
      hydroxysteroid dehydrogenase with tetranitromethane is paralleled by enzyme
      inactivation. With a 10-fold excess of reagent, labeling corresponds to 1.2 nmol
      Tyr/nmol protein chain and is recovered largely in Tyr152, with lesser amounts in
      Tyr251. Tetranitromethane also rapidly inhibits the other two dehydrogenases, but
      they contain Cys residues, preventing direct correlation with Tyr modification.
      Together, the proteolysis and chemical modifications highlight three segments of
      short-chain dehydrogenase subunits, one mid-chain, containing Tyr152 of the
      steroid dehydrogenase (similar numbers in the other enzymes), strictly conserved
      and apparently close to the enzyme active site, the other around position 195,
      sensitive to proteolysis and affected by coenzyme binding, while the third is
      close to the C-terminus.

PMID- 1396702
TI  - Human placental alkaline phosphatase. An improved purification procedure and
      kinetic studies.
AB  - An improved method for the purification of human placental alkaline phosphatase
      is described. The partially purified enzyme from Sigma was further purified by
      successive Concanavalin A-Sepharose and Q-Sepharose chromatography. The whole
      procedure may be completed in one working day. Highly purified enzyme was
      obtained with a 39% yield. The intrinsic fluorescence of the enzyme decreased at
      elevated temperature. The conformation of the enzyme molecule was studied by the
      fluorescence quenching technique. Upward Stern-Volmer plots were obtained for the
      quenching data which suggested that, in addition to collisional quenching, static
      quenching was involved in the quenching mechanism. The dynamic and static
      quenching constants were found to be 0.7 +/- 0.16 M-1 and 0.44 +/- 0.1 M-1,
      respectively, using acrylamide as the quenching agent. The corresponding values
      were 0.43 +/- 0.23 M-1 and 0.84 +/- 0.18 M-1, respectively, with KI as the
      quenching agent. Mg2+ and PO4(3-) induced protein conformational changes which
      altered both the dynamic and static quenching constants. Mg2+ was found to be a
      non-essential activator for the placental alkaline-phosphatase-catalyzed
      hydrolysis of 4-nitrophenyl phosphate. At pH 9.8, Mg2+ increased Vmax by 1.2-fold
      without affecting the Kd of the substrate. The tetranitromethane-modified enzyme
      showed slower migration toward the anode on electrophoresis and increased Kd for
      Mg2+.

PMID- 1396703
TI  - 10N-nonyl acridine orange interacts with cardiolipin and allows the
      quantification of this phospholipid in isolated mitochondria.
AB  - The acridine orange derivative, 10N-nonyl acridine orange, is an appropriate
      marker of the inner mitochondrial membrane in whole cells. We use membrane model
      systems to demonstrate that 10N-nonyl acridine orange binds to negatively charged
      phospholipids (cardiolipin, phosphatidylinositol and phosphatidylserine). The
      stoichiometry has been found to be 2 mol 10N-nonyl acridine orange/mol
      cardiolipin and 1 mol dye/mol phosphatidylserine or phosphatidylinositol, while,
      with zwitterionic phospholipids, significant binding could not be detected. The
      affinity constants were 2 x 10(6) M-1 for cardiolipin-10N-nonyl-acridine-orange
      association and only 7 x 10(4) M-1 for that of phosphatidylserine and
      phosphatidylinositol association. The high affinity of the dye for cardiolipin
      may be explained by two essential interactions; firstly an electrostatic
      interaction between the quaternary ammonium of nonyl acridine orange and the
      ionized phosphate residues of cardiolipin and secondly, hydrophobic interactions
      between adjacent chromophores. A linear relationship was demonstrated between the
      cardiolipin content of model membranes and the incorporated dye. Consequently, a
      convenient and rapid method for cardiolipin quantification in membranes was
      established and applied to the cardiolipin-containing organelle, the
      mitochondrion.

PMID- 1396705
TI  - Isolation and structural characterization of a mono-sulfated
      isoglobotetraosylceramide, the first sulfoglycosphingolipid of the isoglobo
      series, from rat kidney.
AB  - A novel sulfoglycosphingolipid based on the isoglobo-series core structure was
      isolated from rat kidney and purified by column chromatographies with DEAE
      Sephadex and silica beads. The structure was characterized by solvolysis,
      compositional analysis, proton NMR spectroscopy, Fourier-transform infrared
      spectroscopy, methylation analysis and liquid secondary ion mass spectrometry
      (LSIMS). The characteristic fragment ions for a sulfate and a sulfated N
      acetylhexosamine were observed in LSIMS spectra. The two-dimensional chemical
      shift-correlated spectroscopy (COSY) and nuclear Overhauser enhancement
      spectroscopy experiments evidenced the presence of a 3-O-sulfated N
      acetylgalactosamine and a Gal alpha 1-3Gal structure in the molecule. The major
      ceramide consisted of 4-hydroxysphinganine linked to a C24 nonhydroxy fatty acid,
      deduced from both compositional analysis and LSIMS. From the above results, the
      following structure was established for this glycolipid: HSO3-3GalNAc beta 1-3Gal
      alpha 1-3Gal beta 1-4Glc beta 1-1Cer, isoglobotetraosylceramide (iGb4Cer) IV3
      sulfate. Rat kidney also contained globotetraosylceramide (Gb4Cer) IV3-sulfate
      which has a carbohydrate core identical to that from human kidney. The yields of
      iGb4Cer IV3-sulfate and Gb4Cer IV3-sulfate were 0.27 and 0.07 nmol/g wet tissue,
      respectively.

PMID- 1396704
TI  - Altered plasma membrane H(+)-ATPase from the Dio-9-resistant pma1-2 mutant of
      Schizosaccharomyces pombe.
AB  - The pma1-2 mutation affecting the plasma membrane H(+)-ATPase of
      Schizosaccharomyces pombe has been selected for resistance to the antibiotic Dio
      9. In membrane fractions purified from glucose-starved cells, the mutant ATPase
      activity is reduced by 96%, is insensitive to inhibition by vanadate and has a pH
      profile displaced in the acidic pH range when compared to the wild type. The
      maximum velocity of the H(+)-ATPase activity of plasma membranes from glucose
      activated pma1-2 cells is activated 20-fold. This is in striking contrast with
      the wild-type ATPase activity, the maximal velocity of which is not affected by
      glucose. However, similar to the wild-type enzyme, glucose activation of the pma1
      2 mutant H(+)-ATPase reduces the Km for MgATP 9-2 mM and shifts the optimal pH
      from 4.8 to 6.0-6.5. The pma1-2 mutation modifies Lys250 to a threonine, which is
      highly conserved in fungal and plant H(+)-ATPases. These results, compared to
      those reported for mutations of neighbour residues in yeast or mammalian P-type
      ATPases, suggest that Lys250 could play a significant role, not only in phosphate
      binding and/or in the E1P-E2P conformational isomerisation, but also in glucose
      activation of the H(+)-ATPase.

PMID- 1396706
TI  - Footprinting studies of DNA-sequence recognition by nogalamycin.
AB  - We have studied the DNA sequence binding preference of the antitumour antibiotic
      nogalamycin by DNase-I footprinting using a variety of DNA fragments. The DNA
      fragments were obtained by cloning synthetic oligonucleotides into longer DNA
      fragments and were designed to contain isolated ligand-binding sites surrounded
      by repetitive sequences such as (A)n.(T)n and (AT)n. Within regions of (A)n.(T)n,
      clear footprints are observed with low concentrations of nogalamycin (< 5
      microM), with apparent binding affinities for tetranucleotide sequences which
      decrease in the order TGCA > AGCT = ACGT > TCGA. In contrast, within regions of
      (AT)n, the ligand binds best to AGCT; binding to TCGA and TGCA is no stronger
      than to alternating AT. Within (ATT)n, the preference is for ACGT > TCGA.
      Although each of these binding sites contains all four base pairs, there is no
      apparent consensus sequence, suggesting that the selectivity is affected by local
      DNA dynamic and structural effects. At higher drug concentrations (> 25 microM),
      nogalamycin prevents DNAse-I cleavage of (AT)n but shows no interaction with
      regions of (AC)n.(GT)n. Regions of (A)n.(T)n, which are poorly cut by DNase I,
      show enhanced rates of cleavage in the presence of low concentrations of
      nogalamycin, but are protected from cleavage at higher concentrations. We suggest
      that this arises because drug binding to adjacent regions distorts the DNA to a
      structure which is more readily cut by the enzyme and which is better able to
      bind further ligand molecules.

PMID- 1396707
TI  - Tissue selectivity of pravastatin sodium, lovastatin and simvastatin. The
      relationship between inhibition of de novo sterol synthesis and active drug
      concentrations in the liver, spleen and testis in rat.
AB  - Tissue selectivity of pravastatin sodium (pravastatin), lovastatin and
      simvastatin, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors was examined by
      measuring inhibition of de novo sterol synthesis and active drug concentrations
      in the liver, spleen and testis in rats after a single oral administration (25
      mg/kg) of these drugs. Regarding tissue drug concentrations, all three drugs were
      liver selective: concentrations of drugs in the liver were about ten-times higher
      than those in the spleen and testis. On the other hand, pravastatin was far more
      liver selective in inhibiting sterol synthesis than two other inhibitors:
      pravastatin inhibited de novo sterol synthesis in the liver but minimally in the
      spleen and testis, whereas lovastatin and simvastatin inhibited in all three
      tissues. Microautoradiographic and in vitro cellular-uptake studies demonstrated
      that pravastatin remained in the extracellular space in the spleen, whereas the
      other drugs entered the cell. We conclude that pravastatin exhibits a liver
      selective inhibition of sterol synthesis because the agent permeates the cell
      membrane in the liver, but not in non-hepatic tissues.

PMID- 1396709
TI  - Purification and partial characterization of a thermostable trithionate hydrolase
      from the acidophilic sulphur oxidizer Thiobacillus acidophilus.
AB  - Cell-free extracts of Thiobacillus acidophilus catalysed the quantitative
      conversion of trithionate (S3O6(2-) to thiosulphate and sulphate. A continuous
      assay for quantification of experimental results was based on the difference in
      absorbance between trithionate and thiosulphate at 220 nm. Trithionate hydrolase
      was purified to near homogeneity from cell-free extracts of T. acidophilus. The
      molecular masses of the native enzyme and the subunit were 99 kDa (gel
      filtration) and 34 kDa (SDS/PAGE). The purified enzyme has a pH optimum of 3.5
      4.5 and a temperature optimum of 70 degrees C. Enzyme activity was stimulated by
      sulphate. The stimulation of the enzyme activity by sulphate was half maximal at
      a concentration of 0.23 M. The Km for trithionate is 70 microM at 30 degrees C
      and 270 microM at 70 degrees C. Enzyme activity was lost after 36 days at 0
      degrees C, 27 days at 70 degrees C; but after 97 days at 30 degrees C, 40% of the
      initial activity was still present: The enzyme activity was inhibited by mercury
      chloride, N-ethylmaleimide, thiosulphate and tetrathionate. Tetrathionate S4O6(2
      ) was not hydrolysed by trithionate hydrolase.

PMID- 1396708
TI  - Chicken vigilin gene organization and expression pattern. The domain structure of
      the protein is reflected by the exon structure.
AB  - Chicken vigilin was identified as a member of an evolutionary-conserved protein
      family with a unique repetitive domain structure. 14 tandemly repeated domains
      are found in chicken vigilin, all of which consist of a conserved sequence motif
      (subdomain A) and a potential alpha-helical region (subdomain B) [1]. We have
      established the physical structure of the chicken vigilin gene by restriction
      fragment analysis and DNA sequencing of overlapping clones isolated from a phage
      lambda genomic DNA library. The chicken vigilin gene is a single-copy gene with a
      total of 27 exons which are distributed over a region of some 22 kbp. Exon 1
      codes for a portion of the 5' untranslated region, exon 2 contains the
      translation start point and forms, along with exons 3 and 4, the N-terminal non
      domain region. Exons 5-25 encode the vigilin domains 1-14 and the remaining exons
      26 and 27 contain the non-domain C-terminal as well as the untranslated regions.
      The domain structure of the protein is reflected in the positioning of introns
      which demarcate individual domains. While domains 1-3 and 8-10 are each encoded
      by a single exon (5-7, 16-18); all other domains are contained in a set of two
      exons which are separated by introns interspersed at variable positions of the
      DNA segment coding for the conserved sequence motif. In conclusion, the data
      presented suggest that the chicken vigilin gene evolved by amplification of a
      primordial exon unit coding for the fundamental bipartite vigilin domain.

PMID- 1396710
TI  - Isolation of tocopherol-binding proteins from the cytosol of smooth muscle A7r5
      cells.
AB  - Cultured smooth muscle A7r5 cells were able to take up alpha-tocopherol (32 +/-
      1.2 nmol/mg protein) the largest part of which (60%) was present in the cytosolic
      fraction. Using a tocopherol-based affinity chromatography and alpha-, beta-,
      gamma-, and delta-tocopherols as eluants, three polypeptides of molecular masses
      81, 58 and 31 kDa were eluted. This preparation had alpha-[3H]tocopherol binding
      capability. The 58-kDa polypeptide could also be eluted by chromanol and the 81
      kDa polypeptide could be eluted also by phytol. The 81-kDa polypeptide had the
      unique P-E-E-D-Q-X-Q-Y N-terminal sequence.

PMID- 1396711
TI  - Purification and characterization of a novel enzyme, arylalkyl acylamidase, from
      Pseudomonas putida Sc2.
AB  - A novel enzyme, arylalkyl acylamidase, which shows a strict specificity for N
      acetyl arylalkylamines, but not acetanilide derivatives, was purified from the
      culture broth of Pseudomonas putida Sc2. The purified enzyme appeared to be
      homogeneous, as judged by native and SDS/PAGE. The enzyme has a molecular mass of
      approximately 150 kDa and consists of four identical subunits. The purified
      enzyme catalyzed the hydrolysis of N-acetyl-2-phenylethylamine to 2
      phenylethylamine and acetic acid at the rate of 6.25 mumol.min-1.mg-1 at 30
      degrees C. It also catalyzed the hydrolysis of various N-acetyl arylalkylamines
      containing a benzene or indole ring, and acetic acid arylalkyl esters. The enzyme
      did not hydrolyze acetanilide, N-acetyl aliphatic amines, N-acetyl amino acids, N
      acetyl amino sugars or acylthiocholine. The apparent Km for N-acetylbenzylamine,
      N-acetyl-2-phenylethylamine and N-acetyl-3-phenylpropylamine are 41 mM, 0.31 mM
      and 1.6 mM, respectively. The purified enzyme was sensitive to thiol reagents
      such as Ag2SO4, HgCl2 and p-chloromercuribenzoic acid, and its activity was
      enhanced by divalent metal ions such as Zn2+, Mg2+ and Mn2+.

PMID- 1396712
TI  - Purification and characterization of a novel lactonohydrolase, catalyzing the
      hydrolysis of aldonate lactones and aromatic lactones, from Fusarium oxysporum.
AB  - A novel lactonohydrolase, an enzyme that catalyzes the hydrolysis of aldonate
      lactones to the corresponding aldonic acids, was purified 10-fold to apparent
      homogeneity, with a 61% overall recovery, from Fusarium oxysporum AKU 3702,
      through a purification procedure comprising DEAE-Sephacel, octyl-Sepharose CL-4B
      and hydroxyapatite chromatographies and crystallization. The molecular mass of
      the native enzyme, as estimated by high-performance gel-permeation
      chromatography, is 125 kDa, and the subunit molecular mass is 60 kDa. The enzyme
      contains 15.4% (by mass) glucose equivalent of carbohydrate, and about 1 mol
      calcium/subunit. The enzyme hydrolyzes aldonate lactones, such as D-galactono
      gamma-lactone and L-mannono-gamma-lactone, stereospecifically. Furthermore, it
      can catalyze the asymmetric hydrolysis of D-pantoyl lactone, which is a promising
      chiral building block for the chemical synthesis of D-pantothenate. These
      reactions are reversible, and the reaction equilibrium at pH 6.0 has a molar
      ratio of nearly 1:1 with D-pantoyl lactone and D-pantoic acid. The Km and Vmax
      for D-galactono-gamma-lactone are 3.6 mM and 1440 U/mg, respectively, and those
      for D-galactonate are 52.6 mM and 216 U/mg, respectively. The enzyme also
      irreversibly hydrolyzes several aromatic lactones, such as dihydrocoumarin and
      homogentisic-acid lactone.

PMID- 1396713
TI  - Purification and biochemical characterization of the EcaI DNA methyltransferase.
AB  - The EcaI GGTNACC-specific DNA-adenine modification methyltransferase has been
      purified to apparent homogeneity. The active form of the DNA methyltransferase is
      a single polypeptide. The enzyme has a pH optimum at pH 8.0 and a temperature
      optimum at 25 degrees C. EcaI DNA methyltransferase transfers one methyl group to
      the adenine of the recognition site in a single binding event. The Km was 170 nM
      for DNA and 1.8 microM for the methyl donor S-adenosylmethionine. Methylated DNA
      is a competitive inhibitor with respect to DNA (Ki = 3.5 nM). The other product
      of the DNA-methylation reaction, S-adenosylhomocysteine was found to be a
      competitive inhibitor with respect to S-adenosylmethionine (Ki = 2.7 microM). The
      S-adenosylmethionine analog sinefungin was shown to be a very strong inhibitor
      (Ki = 3.5 nM) of the DNA methyltransferase reaction.

PMID- 1396714
TI  - Characterization and molecular cloning of a flavoprotein catalyzing the synthesis
      of phytofluene and zeta-carotene in Capsicum chromoplasts.
AB  - In plants, zeta-carotene is the first visible carotenoid formed in the
      biosynthetic pathway through the following two-step desaturation reaction:
      phytoene-->phytofluene--> zeta-carotene. Using Capsicum annuum chromoplast
      membranes and the reconstitution system previously described [Camara, B., Bardat,
      F. & Moneger, R. (1982) Eur. J. Biochem. 127, 255-258], we have attempted to
      purify the desaturase(s) catalyzing these reactions. The two activities were
      coincidental during all the purification procedures. Only a single polypeptide
      with 56 +/- 2 kDa was detected by SDS/PAGE of all active fractions. The enzyme
      contained protein-bound FAD. Antibodies raised against the purified polypeptide
      selectively precipitated the phytoene and the phytofluene desaturase activities,
      thus demonstrating that the enzyme is a bifunctional flavoprotein. The antibodies
      were used to isolate a full-length cDNA clone from which was deduced the primary
      structure of the desaturase which contains a characteristic dinucleotide-binding
      site. Overexpression of the cDNA in Escherichia coli allowed the production of a
      recombinant desaturase which had all the properties of the chromoplast
      desaturase. The phytoene/phytofluene desaturase mRNA levels were extremely low in
      green fruits and increased slightly before detectable carotenoid synthesis and
      remained constant throughout ripening. However, the desaturase activity and
      protein levels were found to increase significantly during the chloroplast to
      chromoplast transition in C. annuum fruits.

PMID- 1396715
TI  - Substrate specificity of small-intestinal lactase. Assessment of the role of the
      substrate hydroxyl groups.
AB  - Lactase-phlorizin hydrolase is a disaccharidase present in the small intestine of
      mammals. This enzyme has two active sites, one being responsible for the
      hydrolysis of lactose. Lactase activity is thought to be selective towards
      glycosides with a hydrophilic aglycon. In this work, we report a systematic study
      on the importance of each hydroxyl group in the substrate molecule for lactase
      activity. For this purpose, all of the monodeoxy derivatives of methyl beta
      lactoside and other lactose analogues are studied as lactase substrates. With
      respect to the galactose moiety, it is shown here that HO-3' and HO-2' are
      necessary for hydrolysis of the substrates by lactase. Using these chemically
      modified substrates, it has been confirmed that lactase does not behave as a
      typical beta-galactosidase, since it does not show an absolute selectivity with
      respect to substitution and stereochemistry at C4' in the galactose moiety of the
      substrate. However, the glucose moiety, in particular the HO-6, appears to be
      important for substrate hydrolysis, although none of the hydroxyl groups seemed
      to be essential. In order to differentiate both activities of the enzyme, a new
      assay for the phlorizin-hydrolase activity has also been developed.

PMID- 1396716
TI  - Fast kinetics studies of Escherichia coli electrotransformation.
AB  - Direct gene transfer is achieved in Escherichia coli by use of square wave
      electric pulsing. As observed by video monitoring, the field pulse causes
      bacteria to orientate parallel to the field lines. Rapid kinetic turbidity
      changes indicate that this process happens quickly. In these circumstances, and
      in pulsing conditions prone to inducing transformation, only caps are affected by
      the field. Considerable cytoplasmic ion leakage occurs during the pulse,
      affecting the interfacial ionic concentration. The pulsing-buffer osmolarity has
      to be close to that used with protoplasts. Contact between the plasmid and the
      bacteria can be very short before the pulse but must be present during the pulse.
      The plasmid remains accessible to externally added DNases up to 5 days after the
      pulse, suggesting that the transfer step is slow. Electric-field-mediated
      transfer can be described in two steps: the anchoring process during the pulse,
      followed by the crossing of the membrane.

PMID- 1396717
TI  - Effect of anisotonic cell-volume modulation on glutathione-S-conjugate release, t
      butylhydroperoxide metabolism and the pentose-phosphate shunt in perfused rat
      liver.
AB  - 1. Addition of 1-chloro-2,4-dinitrobenzene to isolated perfused rat liver results
      in the rapid formation of its glutathione-S-conjugate [S-(2,4
      dinitrophenyl)glutathione], which is released into both, bile and effluent
      perfusate. Anisotonic perfusion did not affect total S-conjugate formation, but
      release of the S-conjugate into the perfusate was increased (decreased) following
      hypertonic (hypotonic) exposure at the expense of excretion into bile.
      Stimulation of S-conjugate release into the perfusate following hypertonic
      exposure paralleled the time course of volume-regulatory net K+ uptake. 2. Basal
      steady-state release of oxidized glutathione (GSSG) into bile was 1.30 +/- 0.12
      nmol.g-1.min-1 (n = 18) during normotonic (305 mOsmol/l) perfusion and was 3.8 +/
      0.3 nmol.g-1.min-1 in the presence of t-butylhydroperoxide (50 mumol/l).
      Hypotonic exposure (225 mOsmol/1) lowered both, basal and t-butylhydroperoxide
      (50 mumol/l)-stimulated GSSG release into bile by 35% and 20%, respectively,
      whereas hypertonic exposure (385 mOsmol/l) increased. Anisotonic exposure was
      without effect on t-butylhydroperoxide removal by the liver. GSSG release into
      bile also decreased by 33% upon liver-cell swelling due to addition of glutamine
      plus glycine (2 mmol/l, each). 3. Hypotonic exposure led to a persistent
      stimulation 14CO2 production from [1-14C]glucose by about 80%, whereas 14CO2
      production from [6-14C]glucose increased by only 10%. Conversely, hypertonic
      exposure inhibited 14CO2 production from [1-14C]glucose by about 40%, whereas
      14CO2 production from [6-14C]glucose was unaffected. The effect of anisotonicity
      on 14CO2 production from [1-14C]glucose was also observed in presence of t
      butylhydroperoxide (50 mumol/l), which increased 14CO2 production from [1
      14C]glucose by about 40%. 4. t-Butylhydroperoxide (50 mumol/l) was without
      significant effect on volume-regulatory K+ fluxes following exposure to hypotonic
      (225 mOsmol/l) or hypertonic (385 mOsmol/l) perfusate. Lactate dehydrogenase
      release from perfused rat liver under the influence of t-butylhydroperoxide was
      increased by hypertonic exposure compared to hypotonic perfusions. 5. The data
      suggest that hypotonic cell swelling stimulates flux through the pentose
      phosphate pathway and diminishes loss of GSSG under conditions of mild oxidative
      stress. Hypotonically swollen cells are less prone to hydroperoxide-induced
      lactate dehydrogenase release than hypertonically shrunken cells. Hypertonic cell
      shrinkage stimulates the excretion of glutathione-S-conjugates into the
      sinusoidal circulation at the expense of biliary secretion.

PMID- 1396718
TI  - Regulation of insulin-like-growth-factor-II gene expression in rat liver cells.
AB  - The rat insulin-like-growth-factor-(IGF)-II gene is expressed at high levels
      during embryonic and fetal life and at low levels in adult animals. To study the
      regulation of IGF-II gene expression, we analyzed the synthesis and localization
      of the IGF-II transcripts in cultured rat liver cells either expressing (BRL3A
      cells) or not expressing (BRL30E and FAO cells) the IGF-II mRNA. The IGF-II gene
      is transcribed at a similar rate in expressing and non-expressing cells, whereas
      its nuclear and cytoplasmic RNA levels are diversely distributed in the cells.
      IGF-II RNA is more abundant in the cytoplasmic than in the nuclear RNA fraction
      of BRL3A cells and is present in the nucleus but not in the cytoplasm of the FAO
      cells. However, both precursor and mature IGF-II nuclear RNA levels are reduced
      in FAO cells. Our data indicate that the IGF-II gene expression is regulated by
      mechanisms affecting the subcellular distribution and the abundance of the
      transcripts.

PMID- 1396720
TI  - Relationship between the major protein kinase C substrates acidic 80-kDa protein
      kinase-C substrate (80K) and myristoylated alanine-rich C-kinase substrate
      (MARCKS). Members of a gene family or equivalent genes in different species.
AB  - Two major protein-kinase-C (PKC) substrates have been described in the
      literature; an 87-kDa bovine and human PKC substrate, called MARCKS, and an
      acidic 80-kDa PKC substrate, isolated from rat brain and Swiss 3T3 cells, termed
      80K. Since there is only 66-74% sequence similarity between MARCKS and 80K, we
      have further investigated their relationship in this study. Southern-blot
      experiments with gene-specific probes demonstrated the presence of the 80K, but
      not MARCKS, gene in the mouse genome. Furthermore, polymerase-chain-reaction
      (PCR) analyses using three pairs of primers that specifically recognise either
      80K, MARCKS or conserved sequences of both genes, revealed the presence of only
      the 80K gene in the mouse and rat genomes and only the MARCKS gene in the bovine
      and human genomes with mRNA expression in the corresponding brain tissues.
      Northern-blot analysis of a variety of tissues indicated that both 80K and MARCKS
      have similar patterns of expression. Most components of signal-transduction
      pathways are present in multiple molecular isoforms as members of a gene family.
      In contrast, the findings presented in this study indicate that rodent 80K and
      bovine and human MARCKS are not distinct members of a gene family, but represent
      the equivalent substrates in different species.

PMID- 1396719
TI  - Redox properties of the iron-sulfur clusters in activated Fe-hydrogenase from
      Desulfovibrio vulgaris (Hildenborough).
AB  - The periplasmic Fe-hydrogenase from Desulfovibrio vulgaris (Hildenborough)
      contains three iron-sulfur prosthetic groups: two putative electron transferring
      [4Fe-4S] ferredoxin-like cubanes (two F-clusters), and one putative Fe/S
      supercluster redox catalyst (one H-cluster). Combined elemental analysis by
      proton-induced X-ray emission, inductively coupled plasma mass spectrometry,
      instrumental neutron activation analysis, atomic absorption spectroscopy and
      colorimetry establishes that elements with Z > 21 (except for 12-15 Fe) are
      present in 0.001-0.1 mol/mol quantities, not correlating with activity.
      Isoelectric focussing reveals the existence of multiple charge conformers with pI
      in the range 5.7-6.4. Repeated re-chromatography results in small amounts of
      enzyme of very high H2-production activity determined under standardized
      conditions (approximately 7000 U/mg). The enzyme exists in two different
      catalytic forms: as isolated the protein is 'resting' and O2-insensitive; upon
      reduction the protein becomes active and O2-sensitive. EPR-monitored redox
      titrations have been carried out of both the resting and the activated enzyme. In
      the course of a reductive titration, the resting protein becomes activated and
      begins to produce molecular hydrogen at the expense of reduced titrant.
      Therefore, equilibrium potentials are undefined, and previously reported apparent
      Em and n values [Patil, D. S., Moura, J. J. G., He, S. H., Teixeira, M, Prickril,
      B. C., DerVartanian, D. V., Peck, H. D. Jr, LeGall, J. & Huynh, B.-H. (1988) J.
      Biol. Chem. 263, 18,732-18,738] are not thermodynamic quantities. In the
      activated enzyme an S = 1/2 signal (g = 2.11, 2.05, 2.00; 0.4 spin/protein
      molecule), attributed to the oxidized H cluster, exhibits a single reduction
      potential, Em,7 = -307 mV, just above the onset potential of H2 production. The
      midpoint potential of the two F clusters (2.0 spins/protein molecule) has been
      determined either by titrating active enzyme with the H2/H+ couple (E,m = -330
      mV) or by dithionite-titrating a recombinant protein that lacks the H-cluster
      active site (Em,7.5 = -340 mV). There is no significant redox interaction between
      the two F clusters (n approximately 1).

PMID- 1396721
TI  - Synovial protein kinase C and its apparent insensitivity to interleukin-1.
AB  - Lapine synovial fibroblasts produce prostaglandin E2 (PGE2) and neutral
      metalloproteinases in response to phorbol 12-myristate 13-acetate (PMA), human
      recombinant interleukin-1 (hrIL-1) and, in an autocrine fashion, in response to
      partially purified preparations of their own cytokines known as cell-activating
      factors (CAF). Here we have examined the possible role of protein kinase C (PKC)
      in these responses. Whereas the 80-kDa substrate for PKC could not be detected in
      synovial fibroblasts, these cells contained a 35-kDa protein which fulfilled the
      criteria for qualifying as a specific substrate of PKC. Translocation assays
      based upon phosphorylation of the 35-kDa protein and Western blotting techniques
      allowed the movement of PKC from the cytosolic to the particulate fraction in
      response to PMA and CAF to be detected but not in response to 4 alpha-PMA or hrIL
      1. Inhibitors of PKC suppressed synovial activation by PMA, partially blocked
      activation by CAF but had no effect on activation by hrIL-1. There thus appear to
      be PKC-dependent and PKC-independent routes to synovial cell activation. Our data
      suggest that IL-1 uses the latter, while CAF contains cytokines which utilize
      both routes.

PMID- 1396722
TI  - Phenotypic transformation of normal rat kidney cells by transforming growth
      factor beta is not paralleled by enhanced production of a platelet-derived growth
      factor.
AB  - Phenotypic transformation of normal rat kidney (NRK) cells requires the concerted
      action of multiple polypeptide growth factors. Serum-deprived NRK cells cultured
      in the presence of epidermal growth factor (EGF) become density-inhibited at
      confluence, but they can be restimulated by a number of defined polypeptide
      growth factors, resulting in phenotypic cellular transformation. Kinetic data
      show that restimulation by transforming growth factor beta (TGF-beta) and
      retinoic acid is delayed when compared to induction by platelet-derived growth
      factor (PDGF), indicating that both TGF beta and retinoic acid may exert their
      growth-stimulating action by an indirect mechanism. Northern blot analysis shows
      that NRK cells express the genes for various polypeptide growth factors,
      including TGF beta 1, PDGF A-chain and basic fibroblast growth factor, but that
      the levels of expression are not affected by TGF beta or retinoic acid treatment.
      NRK cells also secrete low amounts of a PDGF-like growth factor into their
      extracellular medium, but the levels of secretion are insufficient to induce
      mitogenic stimulation and are unaffected by agents inducing phenotypic
      transformation. In combination with studies on the effects of anti-PDGF
      antibodies, it is concluded that phenotypic transformation of NRK cells by TGF
      beta and retinoic acid is not the result of enhanced production of a PDGF-like
      growth factor.

PMID- 1396723
TI  - Regulatory protein phosphorylation of phosphoenolpyruvate carboxylase in the
      facultative crassulacean-acid-metabolism plant Mesembryanthemum crystallinum L.
AB  - Phosphoenolpyruvate PyrP carboxylase (PyrPC) and PyrPC kinase were copurified
      from dark-adapted leaves of the common ice plant Mesembryanthemum crystallinum L.
      with crassulacean-acid metabolism (CAM). Purification by (NH4)2SO4 fractionation,
      chromatography on Fractogel-DEAE and hydroxylapatite resulted in a PyrPC
      preparation with a specific activity of 23-25 U/mg protein and a protein kinase
      activity of 255 mumol Pi.mol-1 PyrPC.s-1. After in vitro phosphorylation, the
      most prominently phosphorylated polypeptide was identified as PyrPC by
      immunoblotting and sequencing. Phosphorylation of PyrPC in vitro by incubation
      with 400 microM MgATP decreased its sensitivity towards malate. When purified in
      the absence of the protease inhibitor chymostatin, PyrPC lost an N-terminal
      sequence of 128 amino acids. Although the carboxylation reaction was unaffected,
      the truncated PyrPC could neither be phosphorylated in vitro nor inhibited by
      malate. This result and data obtained by limited proteolysis concur with the
      hypothesis [Jiao, J.A. & Chollet, R. (1989) Arch. Biochem. Biophys. 283, 300-305]
      that Ser11 is the phosphorylation site of the CAM PyrPC of M. crystallinum. At pH
      7.0, the Km for ATP of the protein kinase was 25 microM; phosphorylation of PyrPC
      was maximal after 30 min at pH 7.0. The kinase showed also activity with histone
      III-S but not with dephosphorylated casein. It was inhibited by malate. The
      results show, that reversible protein phosphorylation is an important factor in
      the regulation of PyrPC in the facultative CAM plant M. crystallinum, similar to
      C4 and constitutive CAM plants.

PMID- 1396725
TI  - Cefuroxime and cefuroxime axetil versus amoxicillin plus clavulanic acid in the
      treatment of lower respiratory tract infections.
AB  - In a large multinational study, the clinical and bacteriological efficacy of
      intravenous cefuroxime 750 mg t.i.d. followed by oral cefuroxime axetil 500 mg
      b.i.d. was compared to that of amoxicillin plus clavulanic acid (CA) administered
      as 1.2 g intravenously t.i.d. followed by 625 mg orally t.i.d. in the treatment
      of lower respiratory tract infections in hospitalised patients. A total of 512
      patients were entered (256 in each treatment group). All were suffering from
      pneumonia or acute exacerbations of chronic bronchitis or bronchiectasis and
      required initial parenteral antibiotic therapy. Parenteral therapy lasted 48 to
      72 h and was followed by five days of oral therapy. The clinical responses in the
      two treatment groups were very similar: 223 of 256 (87.1%) patients were cured or
      improved with cefuroxime/cefuroxime axetil compared to 220 of 256 (85.9%) with
      amoxicillin/CA. Positive pre-treatment sputum samples were obtained from 44% of
      the patients. Clearance rates obtained were again similar: 72.8% with
      cefuroxime/cefuroxime axetil and 70% with amoxicillin/CA. Ten percent of the
      isolates were beta-lactamase producers, similar numbers of which were cleared in
      both groups. Both regimens were generally well tolerated, with only 5% of
      patients treated with the cefuroxime regimen and 4.3% of patients treated with
      amoxicillin/CA experiencing drug-related adverse events. Cefuroxime/cefuroxime
      axetil "follow-on" therapy produces clinical and bacteriological efficacy
      equivalent to that of amoxicillin/CA, with the advantage of twice daily oral
      administration.

PMID- 1396724
TI  - Survey of Escherichia coli septicemia over a six-year period.
AB  - Escherichia coli was the most frequent species isolated from blood cultures in
      the Hospital Covadonga of Oviedo (Spain) over a six-year period (474 episodes,
      15.3% of the total septicemias and 2.7 episodes per 1,000 patients). Escherichia
      coli strains were susceptible in greater than 95% of episodes to cefoxitin,
      cefotaxime, gentamicin, tobramycin and amikacin. In a series of 72 episodes,
      microbiological features and host factors were studied. No endemic stains were
      found. Type 1 fimbria was detected in 73.6% of strains and P-fimbriae in 12.5%,
      without correlation between P-fimbria and urinary infection; 84.7% of the strains
      were resistant to decomplement human serum; 61.1% produced aerobactin and 20.8%
      were hemolytic. Factors such as age, hospital location, metastatic focus and
      surgical treatment were significantly correlated with morbidity and mortality.
      The global mortality rate was 18%, and in 8.3% of cases was directly associated
      with septicemia.

PMID- 1396726
TI  - Cotrimoxazole therapy of Toxoplasma gondii encephalitis in AIDS patients.
AB  - Twenty-four consecutive HIV-positive patients affected by Toxoplasma gondii
      encephalitis received trimethoprim-sulfamethoxazole (cotrimoxazole) as acute
      phase treatment. Two dosage regimens of cotrimoxazole were used: 40 mg/kg/day (12
      patients) or 120 mg/kg/day (12 patients) of total compound (trimethoprim plus
      sulfamethoxazole). Clinical and radiological responses to treatment were
      evaluated, and the product-limit method for survival data analysis was used.
      Eighteen of 24 patients showed both a clinical and radiological response (75%
      response rate). There were no differences in response rates between patients
      receiving the two dosage regimens of cotrimoxazole. Adverse reaction consisted of
      leukopenia (two cases) and skin rash (three cases) which led to the
      discontinuation of the drug in one case. These results suggest that a randomized,
      controlled clinical trial should be carried out comparing cotrimoxazole versus
      sulfadiazine-pyrimethamine in AIDS patients with Toxoplasma gondii encephalitis.

PMID- 1396727
TI  - Prevalence of Chlamydia pneumoniae antibodies in Hungary.
AB  - Investigation of Chlamydia pneumoniae (TWAR) antibodies in paired sera of 120
      patients with various respiratory diseases revealed a prevalence of 4.2% of IgG
      seroconversion. IgG antibody without seroconversion was found in 83.3%. Sera of
      ten patients showed titers as high as 512-1024 or above. Children with no
      respiratory disease and blood donors in Budapest had specific IgG in 46.5% and
      75.2% respectively. Prevalence of IgG antibody in children from the rural areas
      of Hungary was about 50% lower than in children in the capital. The high
      prevalence of persistent IgG, indicating earlier infection, suggests that
      Chlamydia pneumoniae infection may be endemic in Budapest. The small number of
      the serologically confirmed acute infections in hospitalized patients with
      pneumonia leads to the conclusion that the majority of patients with chlamydial
      pneumonia responds to the therapeutic regimen administered by the general
      practitioner and referral to hospital rarely becomes necessary.

PMID- 1396728
TI  - Effects of fluconazole on the sterol and carbohydrate composition of four species
      of Candida.
AB  - The effects of fluconazole, a bis-triazole antifungal agent, on the sterol and
      carbohydrate composition of Candida albicans, Candida tropicalis, Candida krusei
      and Candida parapsilosis were investigated. Exposure of Candida species to
      fluconazole resulted in a profound depletion of ergosterol with a corresponding
      increase in lanosterol content versus control cells. Carbohydrate analysis
      revealed a significant increase in chitin and either a decrease (Candida
      albicans, Candida tropicalis and Candida parapsilosis) or an increase (Candida
      krusei) in glucan content in fluconazole-treated cells. The decreased ergosterol
      and increased lanosterol content is consistent with 14-alpha-demethylase
      inhibition by fluconazole. The increase in cell wall chitin is most likely due to
      deregulation of chitin synthesis secondary to ergosterol depletion in the cell
      membrane. Because chitin, glucan and ergosterol are critical components of the
      fungal cell, perturbation of the production and localization of these components
      by fluconazole is likely to contribute to the selective toxicity of this compound
      to Candida species and other fungi.

PMID- 1396729
TI  - Spleen abscess caused by Eikenella corrodens.
AB  - A case is reported of splenic abscess due to Eikenella corrodens, a gram-negative
      rod which is found as part of normal flora in human mucous surfaces. A 64-year
      old man presented with fever, chills, anorexia and abdominal pain. Abdominal
      ultrasound examination showed a perisplenic fluid collection which was considered
      to be either blood or a subcapsular spleen abscess. The presence of a splenic
      abscess was later confirmed during surgery and a splenectomy was performed.
      Splenic purulent material and blood cultures yielded Eikenella corrodens. The
      patient received cefotaxime for 19 days and was discharged asymptomatic.

PMID- 1396730
TI  - Monitoring of antibiotic resistance in shigellae isolated in The Netherlands 1984
      1989.
AB  - During surveillance of antimicrobial resistance in Shigella strains isolated in
      the Netherlands from 1984 to 1989 and forwarded to the National Institute of
      Public Health and Environmental Protection for typing, sensitivity to twelve
      antimicrobial agents was assessed. High rates of resistance to the older drugs of
      choice in treating shigellosis were found, i.e. ampicillin and trimethoprim
      sulfamethoxazole. Ampicillin resistance varied from 33 to 53% among Shigella
      flexneri strains and from 10 to 17% among Shigella sonnei strains. Trimethoprim
      and trimethoprim-sulfamethoxazole resistance increased from 8% to about 25% among
      Shigella flexneri and from 16 to 46% among Shigella sonnei isolates. All strains
      were susceptible to the newer quinolones, but five strains resistant to nalidixic
      acid showed decreased susceptibility to norfloxacin. Approximately 10% of the
      isolates were resistant to the combination of ampicillin, trimethoprim and
      sulfamethoxazole.

PMID- 1396731
TI  - Retrospective study to determine the diagnostic value of the Widal test in a non
      endemic country.
AB  - The purpose of this study was to determine the usefulness of the Widal test in
      the diagnosis of typhoid fever. Data were obtained by retrospective analysis of
      311 Widal requests covering a six-year period. Nine cases of typhoid infection
      were diagnosed culturally. Of these, only three patients had samples for
      serological examination, all giving indicative titres. Of the 274 evaluated sera,
      26 showed significant agglutinating titres; 23 of them were false positive. These
      results show that routine use of the Widal test is of limited value and should
      only be used for patients in whom repeated cultures remain negative.

PMID- 1396732
TI  - Differential effects of bismuth and salicylate salts on the antibiotic
      susceptibility of Pseudomonas aeruginosa.
AB  - The influence of salicylate or bismuth salts on antibiotic action against
      Pseudomonas aeruginosa was assessed in broth cultures. Sodium salicylate (2.5 mM)
      had no significant effect on the activity of any antibiotic tested. In contrast,
      bismuth compounds (0.5 mM) produced a significant change in the inhibitory
      activity of several antibiotics against all strains. Bismuth salts reduced
      imipenem activity by up to 20-fold, enhanced gentamicin or amikacin activity
      three to five-fold, and enhanced cefpirome or cefepime activity by as much as 10
      fold against antibiotic-sensitive and resistant strains. Bismuth salts had little
      effect on cefoperazone, ceftazidime, or mezlocillin activity. Combining bismuth
      salts with aminoglycosides or fourth-generation cephalosporin antibiotics may
      help to combat the growing problem of resistant Pseudomonas aeruginosa.

PMID- 1396733
TI  - Comparison of a new commercial enzyme immunoassay for rapid detection of
      respiratory syncytial virus.
AB  - Two rapid methods for detection of respiratory syncytial virus in respiratory
      specimens were compared: direct immunofluorescence assay (DFA) with monoclonal
      antibody and an enzyme immunoassay (EIA) (Test-Pack RSV). Ninety-five
      nasopharyngeal washings and aspirates from 51 children were examined; the
      patients were hospitalized during a winter outbreak of RSV infection in the first
      trimester of 1990. A total of 41.0% and 56.8% of these samples were positive by
      EIA and DFA respectively. Considering only the 51 specimens collected at the
      onset of illness, EIA detected 72.5% positive samples and DFA detected 78.4%. In
      comparison with DFA, EIA was 92.5% sensitive and 100% specific for the acute
      phase of illness. When all the samples were taken into account, specificity was
      maintained but sensitivity fell to 72.2%. The results show that both methods are
      useful during the acute phase of the illness, when the viral load is important.
      However, later on in the course of the infection DFA appears to be more sensitive
      than EIA.

PMID- 1396734
TI  - Evaluation of the E test in testing susceptibility of Pseudomonas aeruginosa to
      tobramycin.
AB  - The E test, a new technique for measuring MICs of antimicrobial agents with the
      ease of disc diffusion tests, was evaluated in testing the susceptibility of 94
      clinical isolates of Pseudomonas aeruginosa to tobramycin. The use of the E test
      was found acceptable; 93% of the MIC results were within one log2 dilution step
      and 100% were within two log2 dilution steps when the MICs obtained by the E test
      were compared to those obtained by the conventional agar dilution method. When
      the E test was compared to the broth microdilution method the corresponding
      figures were 84% and 100%, respectively.

PMID- 1396735
TI  - Antibacterial activity of the investigational oral and parenteral cephalosporin
      BK-218.
AB  - BK-218 is a novel cephalosporin with a dual route of administration and spectrum
      of activity most similar to that of second-generation cephalosporins. BK-218 was
      active against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
      catarrhalis but strains resistant to penicillins had higher MICs. BK-218 had
      greater activity (8-fold) than cefuroxime or cefaclor against oxacillin
      susceptible Staphylococcus spp. Moderate BK-218 activity was observed against
      Neisseria gonorrhoeae and commonly isolated Enterobacteriaceae such as
      Escherichia coli (MIC90, 1 mg/l), Klebsiella spp. (MIC90, 2 mg/l), and Proteus
      mirabilis (MIC90, 2 mg/l). The following organisms were generally BK-218
      resistant (MIC90, greater than 16 mg/l): Bacteroides fragilis, Pseudomonas spp.,
      Acinetobacter spp., Xanthomonas maltophilia, Citrobacter spp., Enterobacter spp.,
      indole-positive Proteus, Serratia spp., enterococci and oxacillin-resistant
      staphylococci.

PMID- 1396736
TI  - Septic arthritis due to Oligella urethralis.

PMID- 1396737
TI  - A case of Propionibacterium acnes spinal osteomyelitis.

PMID- 1396738
TI  - A case of biliary tract infection caused by Haemophilus parainfluenzae.

PMID- 1396739
TI  - Serratia fonticola as an infectious agent.

PMID- 1396740
TI  - A case of cellulitis, thrombophlebitis and bacteremia caused by Salmonella group
      E.

PMID- 1396742
TI  - Bacterial colonization of the non-pregnant uterus: a study of pre-menopausal
      abdominal hysterectomy specimens.

PMID- 1396741
TI  - Failure of fluconazole in systemic candidiasis.

PMID- 1396743
TI  - Silent spontaneous retroperitoneal abscess caused by M-type 18 Streptococcus
      pyogenes.

PMID- 1396744
TI  - Preliminary interpretive criteria for the Haemophilus Test Medium method using 30
      micrograms cefepime disks.

PMID- 1396745
TI  - Prevalence studies in nosocomial infections.

PMID- 1396747
TI  - Impact of the changing epidemiology of fungal infections in the 1990s.
AB  - The increase in fungal infections over the past decade is striking. This is
      particularly true for hospitalized patients where the rate of candidal
      bloodstream infection has increased by as much as 487% over the decade of the
      1980s. This increase in fungal infections is accompanied by a significant excess
      mortality and excess length of stay in hospital. The emergence of "new" fungal
      pathogens such as Candida krusei, Torulopsis glabrata, Fusarium and Trichosporon
      beigelii is now recognized as a significant problem in many patient populations.
      The documentation of nosocomial transmission of fungal pathogens and the
      recognition of resistance to both new and established anti-fungal agents poses a
      significant problem entering the 1990s. Continued effort is needed to develop new
      and better therapeutic agents and more effective strategies for prophylaxis of
      endogenous infections and prevention of transmission within the hospital setting.

PMID- 1396748
TI  - Antibiotic sensitivity of the Bacteroides fragilis group in Europe. European
      Study Group.
AB  - Rates of resistance to 12 antibiotics were determined for 1,289 isolates of
      Bacteroides fragilis group submitted in 1988-1989 by 22 laboratories in 15
      European countries. There was no resistance to metronidazole (breakpoint 8 mg/l)
      and only one isolate was resistant to chloramphenicol (breakpoint 8 mg/l).
      Resistance was uncommon for imipenem (0.3% at greater than 4 mg/l),
      amoxicillin/clavulanate (1% at greater than 8 mg/l), cefoxitin (3% at greater
      than 32 mg/l), mezlocillin (6% at greater than 64 mg/l) and clindamycin (9% at
      greater than 4 mg/l). Resistance was the rule for ampicillin (93% at greater than
      4 mg/l), ciprofloxacin (56% at greater than 4 mg/l) and tetracycline (64% at
      greater than 4 mg/l). Bacteroides fragilis, the commonest species, was generally
      the most sensitive: resistance of this organism was uncommon for cefotetan (4% at
      greater than 32 mg/l) and ceftazidime (12% at greater than 32 mg/l) to which the
      other species were more often resistant. There were small but significant
      differences between laboratories and countries for many of the antibiotics.
      Regionally the most striking differences were for clindamycin where resistance in
      Bacteroides fragilis was most common in the South and for tetracycline where
      resistance in Bacteroides fragilis, Bacteroides thetaiotaomicron and Bacteroides
      uniformis was least common in the North.

PMID- 1396746
TI  - Fungal infections in cancer patients: an international autopsy survey.
AB  - In an attempt to estimate the frequency of fungal infections among cancer
      patients, a survey of autopsy examinations was conducted in multiple institutions
      in Europe, Japan and Canada. Fungal infections were identified most often in
      leukemic patients and transplant recipients (25% each). Fifty-eight percent of
      fungal infections were caused by Candida spp. and 30% by Aspergillus spp. There
      was considerable variability in the frequency of fungal infections in different
      countries. Nevertheless, this study clearly demonstrates that fungal infections
      represent a common complication in cancer patients, especially in patients with
      leukemia.

PMID- 1396749
TI  - Use of molecular methods to characterize Moraxella catarrhalis strains in a
      suspected outbreak of nosocomial infection.
AB  - Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of whole cell protein,
      immunoblotting with normal human serum and restriction endonuclease analysis
      using Taq I enzyme were applied to 38 clinically significant isolates of
      Moraxella (Branhamella) catarrhalis obtained during a suspected outbreak of
      nosocomial infection. Each of 18 strains had individual profiles by at least two
      of the three methods (unique strains). The remaining 20 strains were assigned to
      five groups (A-E) on the basis of similarity by at least two of the three
      methods. Isolates within groups A, D and E were homologous by all three methods.
      Immunoblot groups B and C had two distinct whole cell protein profiles (B1 and
      B2) but indistinguishable restriction endonuclease profiles (group B/C). This
      emphasizes the need to use more than one technique in characterizing strains from
      suspected outbreaks of nosocomial infection. Grouped strains were more likely to
      originate from the same hospital ward than unique strains and were associated
      with a significantly longer median time from patient admission to strain
      isolation (14 versus 3.5 days, p less than 0.005). Furthermore, the beta
      lactamase activity was homologous within the groups. The results suggest that
      nosocomial infection involving several distinct Moraxella catarrhalis strains
      persisted over a period of months, involving at least 20 patients on three
      different wards. Such infection is probably common in wards harbouring suitably
      predisposed patients. The mode of transmission remains to be elucidated, but the
      above three techniques possess sufficient reproducibility and discriminatory
      ability to constitute suitable investigative tools.

PMID- 1396751
TI  - Use of a urea breath test versus invasive methods to determine the prevalence of
      Helicobacter pylori in Zaire.
AB  - The prevalence of Helicobacter pylori infection in Zaire was determined by means
      of a [14C] urea breath test in 133 asymptomatic subjects, by culture and
      histological examination of biopsies in 324 consecutive endoscopy patients with
      chronic epigastric complaints, and by both the breath test and culture/histology
      in a subset of 92 patients. Sixty healthy Belgian students or hospital laboratory
      workers were also included for comparison. The prevalence of Helicobacter pylori
      was significantly higher in asymptomatic Zairian subjects (77.4%) than in the
      Belgians (30%; p less than 10(-6)). Infection was also acquired much earlier in
      life in Africans, 66% of the children aged 5 to 9 years already being infected
      versus none of the Belgian subjects below the age of 20 years. In Zaire, however,
      the prevalence of Helicobacter pylori in patients with gastroduodenal disorders
      (87.5%) was similar to that in the group of asymptomatic subjects (77.5%) after
      adjustment for age and other epidemiological parameters (gender, place of
      residency, education level, smoking and drinking habits) in a multivariate
      analysis. The high rate of acquisition of Helicobacter pylori infection in Zaire
      emphasizes the need to consider the baseline prevalence of Helicobacter pylori in
      a defined population when studying its association with various diseases.

PMID- 1396750
TI  - Characterization of cell-bound papain-soluble beta-lactamases in BRO-1 and BRO-2
      producing strains of Moraxella (Branhamella) catarrhalis and Moraxella
      nonliquefaciens.
AB  - In Moraxella (Branhamella) catarrhalis and Moraxella nonliquefaciens strains
      isolated from clinical specimens in the south of Sweden two variants of beta
      lactamase were distinguished by isoelectric focusing (IEF). The BRO-1 (Ravasio
      type) enzyme was the most common in Branhamella catarrhalis, constituting about
      90% of the beta-lactamase found in this species, while the BRO-2 enzyme (1908
      type) was as common as BRO-1 in Moraxella nonliquefaciens. The determinants
      mediating the production of BRO-1 and BRO-2 were both transferable by
      conjugation. Cell-bound beta-lactamase from reference strains producing BRO-1 and
      BRO-2 could be solubilized by papain digestion. The isoelectric point of the
      solubilized enzymes differed distinctly between BRO-1 (pI 6.5) and BRO-2 (pI
      6.9). The molecular species of BRO-1 and BRO-2 released by papain digestion were
      purified by affinity chromatography with phenylboronic acid agarose gel. They had
      identical molecular weights of approximately 28,000. Their kinetic constants were
      indistinguishable for a number of substrates and beta-lactamase inhibitors.

PMID- 1396752
TI  - Prevalence of antibodies to human immunodeficiency virus type 1 and condom use
      among outpatients at a sexually transmitted disease clinic in Rome.
AB  - To assess the prevalence of HIV-1 infection and study selected risk factors among
      patients attending a clinic for sexually transmitted diseases in Rome, 1442
      outpatients seen consecutively between 20 February and 12 December 1989 were
      anonymously tested for anti-HIV-1. An evaluation of the trend of the HIV-1
      infection was attempted by comparing the results of the present study with those
      obtained from a similar sample studied in 1986 in the same clinic. The overall
      estimated prevalence of anti-HIV-1 was 1.2% among heterosexual non-drug user
      subjects and 16.1% among homosexual or bisexual men. The anti-HIV-1
      seropositivity was significantly higher in heterosexual subjects who reported
      sexual contact with intravenous drug users, as compared with those who did not
      report such exposure (12.5% vs 0.8%, p less than 0.005). Comparing the present
      data with those of a study conducted in 1986 in the same clinic, a lower
      prevalence of anti-HIV-1 was found among heterosexual subjects (1.2% in 1989 vs
      6.0% in 1986, p less than 0.001). The availability after 1986 of several
      outpatient facilities attracting seropositive subjects and a change in the sexual
      behaviour of anti-HIV-1 positive subjects could explain this finding. Twenty
      percent of the heterosexual subjects and 62% of the homosexual or bisexual men
      reported consistent use of condoms.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396754
TI  - Determination of neutralizing antibodies and specific immunoglobulin isotype
      levels in infants after vaccination against diphtheria.
AB  - Serum samples were obtained from 44 infants vaccinated against diphtheria at the
      ages of 3, 5 and 12 months with an aluminium-adsorbed diphtheria-tetanus toxoid
      vaccine containing 15 Lf units of diphtheria toxoid. Toxin-neutralizing
      antibodies (antitoxin) were measured by the Vero cell assay and IgG, IgM and IgA
      antibodies against diphtheria toxoid by enzyme-linked immunosorbent assay. A
      neutralizing antibody titer of 10 corresponded to 0.01 IU/ml, the level
      considered necessary for short-term protection. Geometric mean neutralizing
      antibody titers at 3, 5, 6, 12, 13 and 30 months were 28, 21, 173, 61, 1076 and
      61. All children had titers of greater than or equal to 10 (greater than or equal
      to 0.01 IU/ml) between 6 and 30 months of age. At 30 months only 48% had titers
      of greater than or equal to 100 (greater than or equal to 0.01 IU/ml), the level
      considered necessary for long-term protection. Geometric mean IgG antibody levels
      were 13, 36, 216, 64, 649 and 57. IgG antibodies significantly correlated with
      neutralizing titers and predicted neutralizing antibodies above or below 10 and
      100 with an accuracy of 96 and 82%, respectively. IgG antibodies could not,
      however, be used to predict individual neutralizing antibody titers with great
      accuracy. IgM antibodies were only detected after the third vaccination. IgA
      antibodies were not detected in any serum sample from ten infants tested. In
      conclusion, the Swedish vaccination schedule results in protective antibody
      levels in infants until at least 30 months of age. The decline of the antibody
      titers indicates a need for further studies to establish the duration of
      protection.

PMID- 1396753
TI  - Influence of vaccination schedules and host factors on antibody response
      following hepatitis B vaccination.
AB  - In a prospective multicentre trial, the influence of schedule, compliance, age,
      sex and weight on the antibody response to hepatitis B vaccination was
      investigated. Comparison of the vaccination schedules 0, 1, 6 months (group 1; n
      = 143) and 0, 1, 2, 12 months (group 2; n = 141) was performed in months 3, 7 and
      12. In addition, the antibody response was compared one month after the third and
      one and six months after the last vaccination. Seroprotection rates (anti-HBs
      greater than 10 IU/l) and antibody titres, given as geometric means (GMTs), were
      higher in group 1 at month 12 as well as one month after completion of three
      immunizations. More vaccinees of group 2, however, showed seroprotection at month
      3 with higher GMTs. In addition, GMTs in group 2 were higher both one month and
      six months after the last vaccine dose. Determination of parallel corrected
      correlation factors demonstrated that age was the most important single factor,
      followed by body weight and sex. However, no more than 3% of the variation in the
      GMT can be explained by the influence of age. Due to decreased compliance with
      the four-dose schedule with a drop-out rate of approximately 10% of the
      vaccinees, the total percentage of initial vaccinees who in the end developed
      protective antibody levels was higher in the 0, 1, 6 months schedule. Thus, it
      can be concluded that subjects likely to comply will benefit from the 0, 1, 2, 12
      months schedule as more rapid protection is obtained and the higher antibody
      levels after the booster vaccination at month 12 provide longer protection.
      However, vaccinees whose compliance might be questionable over a period of 12
      months, should be selected for the vaccination 0, 1, 6 months schedule as
      compliance is at a higher level over this period and advantage can be taken of
      the booster effect of the third dose given in month 6.

PMID- 1396755
TI  - Spontaneous bacterial peritonitis caused by Listeria monocytogenes: two case
      reports and literature review.
AB  - Two new cases of spontaneous bacterial peritonitis (SBP) caused by Listeria
      monocytogenes are reported. Listeria monocytogenes was recovered from the ascitic
      fluid but not from the blood cultures of two adult diabetic inpatients with
      hepatic cirrhosis and SBP that had been treated empirically with cefotaxime.
      These two cases add to the 17 cases of Listeria monocytogenes SBP reported
      previously, stressing the relevance of this microorganism to this clinical
      condition. The recovery of Listeria monocytogenes from blood has been achieved in
      only half of the cases reported, suggesting the possibility of a direct
      translocation mechanism. Combinations of amino- or ureidopenicillins with beta
      lactamase inhibitors or carbapenems might be more effective as empiric therapy of
      SBP in cirrhotic patients.

PMID- 1396756
TI  - Isolation of Klebsiella terrigena from clinical specimens.
AB  - In a three-year survey conducted from 1988 to 1990 Klebsiella isolates from human
      clinical specimens were subjected to additional tests to identify any Klebsiella
      terrigena strains. Ten strains of Klebsiella terrigena (0.4%) were found among
      2355 indole-negative Klebsiella isolates. Most of the isolates were recovered
      from the respiratory tract. In the API20EC system almost exclusively biotypes no.
      1777771 and 1777671 were observed. Serotyping revealed capsule types K2, K5 and
      K18 in two strains each. In antibiotic susceptibility tests the strains were
      shown to be comparable in sensitivity to Klebsiella pneumoniae.

PMID- 1396757
TI  - Changes in the susceptibility of Bacteroides fragilis group organisms to various
      antimicrobial agents 1979-1989.
AB  - The in vitro activity of metronidazole, chloramphenicol, clindamycin and 11 beta
      lactam antibiotics against 135 clinical isolates of the Bacteroides fragilis
      group was compared. In addition, changes in the resistance patterns of members of
      the Bacteroides fragilis group isolated at the Hospital Universitario San Carlos
      in Madrid, Spain, between 1979 and 1989 were documented. The most active beta
      lactam drugs were imipenem and beta-lactamase inhibitor combinations. In 1989,
      however, two strains were found to be resistant to imipenem and to all other beta
      lactam agents tested. There was no emergence of resistance to metronidazole.
      Chloramphenicol was very effective: only one resistant strain was detected in
      1979 and no chloramphenicol-resistant isolates were found during the rest of the
      study period. An outbreak of clindamycin resistance was noted in 1982, and the
      first cefoxitin resistant strains were recovered in 1985. The changing patterns
      of susceptibility of anaerobic bacteria to antimicrobial agents and the emergence
      of Bacteroides fragilis strains resistant to new beta-lactam agents suggest that
      periodic antimicrobial susceptibility tests should be performed in order to guide
      the selection of antimicrobial agents for therapy.

PMID- 1396758
TI  - New high-content disks for determination of high-level aminoglycoside resistance
      in clinical isolates of Enterococcus faecalis.
AB  - Disks impregnated with 500 and 1000 micrograms of streptomycin, 1000 micrograms
      of kanamycin and 250 and 500 micrograms of gentamicin were used for detection of
      high-level resistance to aminoglycosides in 120 clinical isolates of Enterococcus
      faecalis. Fifty-seven strains were highly resistant to streptomycin, 80 to
      kanamycin and 41 to gentamicin. Using disks containing 500 micrograms of
      streptomycin, 1000 micrograms of kanamycin and 500 micrograms of gentamicin
      strains resistant to high levels of these drugs (97.9%, 100% and 100%,
      respectively) were accurately detected. Better discrimination between high-level
      and low-level resistance was achieved with a 500 micrograms streptomycin or
      gentamicin disk. Zone-size breakpoints are proposed for detection of high-level
      resistance by disk diffusion.

PMID- 1396759
TI  - Evaluation of a commercial enzyme immunoassay kit for the detection of
      Clostridium difficile toxin A.
AB  - A new enzyme immunoassay (EIA) kit developed for the rapid detection of
      Clostridium difficile toxin A in faecal specimens, Premier (Meridian
      Diagnostics), was evaluated using 101 faecal specimens. Sixty-nine specimens were
      positive for Clostridium difficile by isolation of the organism and by
      cytotoxicity in tissue culture. The EIA for toxin A was positive in 49 of these
      69 cases. No specimen that was negative for cytotoxicity was positive by EIA.
      Eight of the 32 specimens negative by both EIA and cytotoxicity assay yielded
      Clostridium difficile by culture. In five of these cases the cytotoxigenic status
      of the isolate was determined, and four were positive. There was no direct
      relationship between cytotoxin titre and EIA reading.

PMID- 1396760
TI  - Activity of cefpirome combined with beta-lactamase inhibitors and affinity for
      the penicillin-binding proteins of methicillin-resistant Staphylococcus aureus.
AB  - The susceptibility of 47 clinical isolates of methicillin-resistant
      Staphylococcus aureus (MRSA) to cefpirome, ceftazidime and methicillin was
      determined with Isosensitest media, with/without 5% NaCl and incubation at 30
      degrees, 37 degrees and 44 degrees C for 24 and 48 h. At 24 h the MIC50 of
      cefpirome was 8 mg/l compared to 64 mg/l ceftazidime; at 48 h this increased to
      32 mg/l cefpirome. The addition of 10 mg/l clavulanic acid or sulbactam lowered
      the MIC of cefpirome (at 48 h) by greater than four-fold in 23% and 11% of the
      strains, respectively. Cefpirome had primary affinity for penicillin-binding
      protein (PBP) 1 and 2 in five MRSA and one methicillin-susceptible Staphylococcus
      aureus. PBP 2a was present in all MRSA and was not saturated by 64 mg/l
      cefpirome. Clavulanic acid at a concentration of 10 mg/l bound to PBP 2 by
      greater than 50% in all strains, and when combined with cefpirome, the density of
      PBP 2a was also reduced but not completely abolished. The data from this study
      suggests that the mechanism of synergy of a beta-lactamase inhibitor plus a
      cephalosporin for MRSA may be due to an additive effect against PBPs and not just
      inhibition of a beta-lactamase. No cefpirome-resistant mutants could be selected
      from a methicillin-susceptible Staphylococcus aureus, but mutants were selected
      from an MRSA (expressing homogeneous methicillin resistance) for which MICs of
      cefpirome were 8 to 32 mg/l.

PMID- 1396761
TI  - Bacteremia and biliary infection caused by Haemophilus influenzae type e in an
      adult.

PMID- 1396762
TI  - Characterization and antibiotic susceptibility of Pediococcus acidilactici
      strains isolated from neutropenic patients.

PMID- 1396763
TI  - An assessment of serological tests for detection of Helicobacter pylori.

PMID- 1396764
TI  - Effect of antimicrobial therapy on the specific serological response to
      Helicobacter pylori infection.
AB  - The systemic immune response to Helicobacter pylori was studied in 247 infected
      adult patients before antimicrobial therapy and at different intervals following
      therapy. Endoscopy with simultaneous collection of biopsies was performed in all
      patients immediately before treatment, 4 to 6 weeks after the end of therapy and
      6 to 12 months later. A 14C-urea breath test was performed 3 to 6 months after
      the end of treatment. Biopsy specimens were cultured and examined histologically
      using Giemsa stain. Sera were tested for Helicobacter pylori IgG antibodies with
      a commercial enzyme immunoassay using species-specific antigens. Overall,
      Helicobacter pylori was eradicated in 120 patients while the other 127 remained
      infected with the organism. The follow-up period ranged from 4 weeks to 33 months
      (mean 10.2 months). Pretreatment IgG levels did not differ significantly between
      the two groups of patients. Six weeks after the end of treatment a slight but
      definite decrease in the IgG antibody levels was seen irrespective of treatment
      success. In the 127 patients who remained Helicobacter pylori-positive, the level
      of IgG antibodies remained stable or increased with time. A continuous fall in
      antibody levels was observed following bacterial eradication in the other 120
      patients, but the difference in antibody levels between treatment responders and
      nonresponders became significant only more than six months after the end of
      treatment (p = 0.001). Serological testing may be useful for monitoring the
      outcome of long-term treatment of Helicobacter pylori infection and obviate the
      need for endoscopy.

PMID- 1396765
TI  - Serodiagnosis of Helicobacter pylori infections by detection of immunoglobulin G
      antibodies using an immunoblot technique and enzyme immunoassay.
AB  - A transferable solid phase enzyme immunoassay (TSP-EIA) and an immunoblot
      technique were evaluated for the detection of IgG antibodies against Helicobacter
      pylori. Using the biopsy urease test as reference method, the sensitivity and
      specificity of the EIA were 96% and 100%, respectively. Immunoblot analysis was
      carried out by testing sera from patients with a positive urease test who
      suffered from type B gastritis, gastric and duodenal ulcers, and a negative
      control group. The immunoblotted Helicobacter pylori proteins showed reproducible
      immunoreactive bands at molecular weights of 130, 93, 75 and 67 kDa. The
      molecular weight protein fractions of Helicobacter pylori of 180 kDa and higher
      were found to be of minor immunological significance. Proteins of less than 60
      kDa exhibited wide serum-specific variations in reactivity after immunostaining.
      No correlation between specific immunoblot patterns and clinical signs induced by
      Helicobacter pylori infection was observed.

PMID- 1396767
TI  - Evaluation of a fluorescent DNA hybridization assay for the detection of
      Neisseria gonorrhoeae.
AB  - This study evaluates a four-hour fluorescent DNA hybridization assay using both
      known bacterial isolates and clinical specimens. A biotinylated oligonucleotide
      probe from a sequence of the plasmid-encoded gene cppB was used. Hybrids were
      detected by addition of a streptavidin-alkaline phosphatase conjugate, followed
      by incubation for 30 min in a fluorescent substrate for alkaline phosphatase. The
      level of detection of the fluorescent assay was 0.1 pg of cryptic plasmid DNA or
      200 cfu of the plasmid-containing strain NG 34/85 of Neisseria gonorrhoeae. A
      total of 119 reference strains of Neisseria gonorrhoeae and other related
      bacteria were tested for reactivity with the probe. All Neisseria gonorrhoeae
      strains, including eight plasmid-free strains, hybridized with the probe.
      Fluorescence ratios were 2.67 for plasmid-free strains and 3.85 for plasmid
      containing strains. Of the heterologous microorganisms tested, only one of six
      strains of Neisseria cinerea gave a fluorescence ratio above the 2.0 cut-off
      value for positivity with the probe at a cell density of 1 x 10(4) cfu. The probe
      was also evaluated using clinical specimens from 100 patients attending a clinic
      for sexually transmitted diseases. The sensitivity of the assay was 100% while
      the specificity was 97.5%. Positive and negative predictive values were 91.2% and
      100%, respectively. The fluorescent DNA hybridization assay for the detection of
      Neisseria gonorrhoeae described here thus appears to be a highly specific and
      sensitive assay.

PMID- 1396768
TI  - Evaluation of a new commercial system for the identification of
      Enterobacteriaceae and non-fermentative bacteria.
AB  - The performance of a new commercial semi-automatic system (Cobas Micro, Becton
      Dickinson) for identification of gram-negative fermentative and non-fermentative
      bacilli was evaluated using strains of clinical origin belonging to 48 different
      species. Two groups of strains were tested: 510 strains using a long incubation
      period (21 hours) and 158 strains using a short incubation period (5 hours). The
      correct identification rate without additional tests was 95.5% and 94.3% for the
      tests using a long and short incubation period respectively. The findings suggest
      that the system is highly accurate in the identification of most clinically
      important gram-negative rods, but shows some shortcomings in the identification
      of non-fermentative bacteria. The system is easy to use, and with some changes in
      the database and the inclusion of gram-positive and anaerobic bacteria would
      offer a valuable alternative to currently available automatic identification
      systems.

PMID- 1396766
TI  - Serodiagnosis of Helicobacter pylori infections with an enzyme immunoassay using
      the chromatographically purified 120 kilodalton protein.
AB  - A membrane-associated 120 kDa protein of Helicobacter pylori with known species
      specificity was isolated and used in an enzyme immunoassay (EIA) for the
      detection of Helicobacter pylori-specific IgG antibodies in patient sera. The EIA
      was compared with two other methods used for serodiagnosis of Helicobacter pylori
      infections: an EIA using sonicated whole Helicobacter pylori cell antigen and
      Western immunoblot. In a prospective study 127 unselected patients (76 patients
      with antrum gastritis, 51 patients without gastritis) who underwent gastroscopy
      were studied histologically and serologically. The EIA using the purified 120 kDa
      protein had the highest specificity (92%) compared with the EIA using a whole
      cell sonicate of a single Helicobacter pylori strain as antigen (60.7%) and the
      immunoblot (90.2%). The sensitivity was 96%, 100% and 92%, respectively. Sera of
      three control patients reacted strongly in all three methods, indicating possible
      Helicobacter pylori infection with negative histological findings. The EIA using
      the 120 kDa protein as antigen was shown to be a specific and sensitive technique
      for the serodiagnosis of Helicobacter pylori infections.

PMID- 1396769
TI  - Outbreak of Chlamydia pneumoniae infection in four farm families.
AB  - The epidemiology of Chlamydia pneumoniae infection was studied in an outbreak in
      four farm families living close together in Denmark. Eleven of 20 members of the
      families studied had bronchitis or pneumonia characteristic of Chlamydia
      pneumoniae infection. Serologic evidence of Chlamydia pneumoniae as causative
      agent was strengthened by a high incidence of epidemic infection. Transmission
      within families and a high frequency of disease versus asymptomatic infection are
      two findings which deviate from epidemiological patterns of Chlamydia pneumoniae
      infection as currently known.

PMID- 1396770
TI  - Detection of Chlamydia trachomatis by the polymerase chain reaction in young
      patients with acute epididymitis.
AB  - Specimens from 11 patients presenting with acute epididymitis were tested for the
      presence of Chlamydia trachomatis by an enzyme immunoassay (EIA), growth in McCoy
      cells and the polymerase chain reaction (PCR), and for other microorganisms by
      standard laboratory techniques. Chlamydia trachomatis urethral infection was
      detected in four patients by tissue culture, in three patients by EIA and in nine
      patients by PCR. These findings confirm the usually low detection rate of
      Chlamydia trachomatis by conventional tissue culture and EIA. Detection by PCR
      indicated both the diagnostic value of this technique and the importance of this
      organism in epididymitis.

PMID- 1396772
TI  - A case of urinary tract infection caused by Corynebacterium urealyticum and
      coryneform group F1.
AB  - A case of urinary tract infection (UTI) caused by a fastidious, urea-splitting,
      antibiotic-sensitive coryneform, identified as CDC group F1, is described. The
      patient suffered from encrusted cystitis and had had previous and persistent UTIs
      caused by Corynebacterium urealyticum (formerly CDC group D2). Bacteriological
      cure was achieved after one month of treatment with amoxicillin plus
      acetohydroxamic acid.

PMID- 1396771
TI  - Septicemia and hepatic abscess caused by Pediococcus acidilactici.
AB  - A case of postoperative Pediococcus acidilactici septicemia with parallel
      isolation of the organism from hepatic specimens is presented. Laboratory methods
      to identify this vancomycin-resistant gram-positive cocci are described. Very few
      cases of documented infections due to this bacterium have been reported in the
      literature.

PMID- 1396773
TI  - Three cases of opportunistic infection caused by propionic acid producing
      Corynebacterium minutissimum.
AB  - Propionic acid producing strains of Corynebacterium minutissimum were isolated
      from three patients with opportunistic infections. One neutropenic patient was
      undergoing chemotherapy for prolymphocytic leukemia; the other two patients were
      undergoing hemodialysis and peritoneal dialysis respectively. An unusual feature
      of these three strains was their resistance to several antibiotics, which is
      seldom seen in diphtheroids other than Corynebacterium jeikeium and CDC group D2.

PMID- 1396774
TI  - Occurrence and phenotypic properties of verotoxin producing Escherichia coli in
      sporadic cases of gastroenteritis.
AB  - Five verotoxin producing Escherichia coli strains were detected in 405 patients
      with infectious gastroenteritis and 3 such strains were detected in 11 patients
      with the hemolytic uremic syndrome in Switzerland. Production of verotoxin 2 was
      associated with the latter three strains. Four strains reacted with the probe for
      the virulence plasmid of Escherichia coli O157:H7, and six reacted with a
      recently described probe for the eae gene of enteropathogenic Escherichia coli.
      None of the strains was of serotype O157:H7. The methods available at present for
      detecting toxins or toxin genes will reliably detect all such verotoxin producing
      strains.

PMID- 1396776
TI  - Sensitivity of seven commercial assays in the detection of hepatitis B virus type
      2-like infection.
AB  - Two hundred serum samples taken from patients with hepatitis B virus type 2-like
      infections were tested with seven commercial enzyme immunoassay methods for
      detection of HBsAg. Positive results were obtained with all methods in some
      samples, the rate of detection of HBsAg ranging from 9% to 90% for the different
      methods. A direct correlation was found between the analytical sensitivity of a
      method and its ability to yield positive results. It is suggested that these
      findings should be taken into consideration when selecting HBsAg detection
      methods in blood banks in order to avoid transmission of the HBV2 agent to
      recipients of blood or blood products.

PMID- 1396775
TI  - Evaluation of two commercial enzyme immunoassays for the diagnosis of
      Helicobacter pylori infection.
AB  - Sera from 65 patients with upper gastrointestinal tract symptoms and proven
      Helicobacter pylori infection, and from 42 negative controls were tested with two
      commercial EIAs (GAP test, BioRad; and ECP test, Biometra) and two non-commercial
      EIAs, one performed with whole sonicated cells and the other with acid extract of
      Helicobacter pylori as antigen. The GAP assay showed a sensitivity of 83.1% and a
      specificity of 47.6%. The ECP assay showed a sensitivity of 87.7% and a
      specificity of 61.9%. For both non-commercial EIAs these figures were 87.7% and
      88.1%, respectively. Independent of the interpretive criteria established by the
      manufacturers, receiver operating characteristic curves were plotted for better
      evaluation of the four methods. Both commercial tests showed a lower probability
      of yielding a correct diagnosis than the non-commercial tests (p less than 0.05).
      Although commercial EIAs are convenient for the diagnosis of Helicobacter pylori
      infection, the accuracy of the two commercial tests evaluated in this study was
      lower compared to that of the two non-commercial EIAs.

PMID- 1396777
TI  - Post-antibiotic effect of the new streptogramin RP 59500.
AB  - The post-antibiotic effect (PAE) of RP 59500, a new streptogramin antibiotic, was
      determined for Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus
      haemolyticus, Streptococcus pneumoniae, and Streptococcus pyogenes. A 30 min
      exposure of Staphylococcus aureus to 5 micrograms/ml of RP 59500 produced a PAE
      of 1.9-6.9 h, and a 60 min exposure of 2.5 micrograms/ml produced a PAE of 3.2-8
      h. A 30 min exposure of 5 micrograms/ml of RP 59500 of coagulase-negative
      staphylococci produced a PAE of 2.5-7.5 h. PAEs of constitutively erythromycin
      resistant staphylococcal isolates were shorter than were the PAEs of highly
      susceptible isolates. A 30 min exposure to 5 micrograms/ml of RP 59500 produced a
      PAE of 7.5-9.5 h for Streptococcus pneumoniae and a PAE of greater than 18 h for
      Streptococcus pyogenes. RP 59500 produced a longer PAE with Staphylococcus aureus
      than did vancomycin, oxacillin or erythromycin. These results suggest that RP
      59500 may be administered less frequently than would be suggested by its half
      life.

PMID- 1396778
TI  - Comparative in vitro activity of cefdinir (CI-983; FK-482) against staphylococci,
      gram-negative bacilli and respiratory tract pathogens.
AB  - The in vitro activity of cefdinir (CI-983; FK-482), a new oral cephalosporin, was
      compared with that of other antimicrobial agents against clinical isolates of
      staphylococci, gram-negative bacilli and common respiratory tract pathogens.
      Cefdinir (MIC90 less than or equal to 2.0 micrograms/ml) was more active than
      cefixime (MIC90 greater than 64 micrograms/ml) and equally as active as
      cefuroxime (MIC90 2.0 micrograms/ml) against oxacillin-susceptible staphylococci.
      Cefdinir was active against Haemophilus influenzae, including beta-lactamase
      producers (MIC90 0.5 microgram/ml), Moraxella catarrhalis (MIC90 less than or
      equal to 0.12 microgram/ml), Streptococcus pneumoniae (MIC90 less than or equal
      to 0.06 microgram/ml) and Streptococcus pyogenes (MIC90 less than or equal to
      0.06 microgram/ml). The activity of cefdinir against gram-negative bacilli was
      variable; organisms with chromosomal cephalosporinases were often resistant.

PMID- 1396779
TI  - Comparative in vitro activity and beta-lactamase stability of RU29246, the active
      metabolite of HR916B.
AB  - HR 916B is a new orally absorbed cephalosporin. In tests its active metabolite,
      RU29246, inhibited Streptococcus pyogenes, Streptococcus agalactiae and
      Streptococcus pneumoniae at less than or equal to 0.12 micrograms/ml, which is
      similar to the antibacterial activity of cefuroxime, and was more active than
      cefaclor. It was also more active (MIC 2 micrograms/ml) than cefixime,
      cefuroxime, cefaclor and cefotaxime against staphylococci. RU29246 inhibited
      Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, Klebsiella
      oxytoca, Proteus mirabilis, Providencia stuartii and Salmonella spp. at less than
      or equal to 1 microgram/ml, thus being more active than cefuroxime and cefaclor,
      but was less active than cefixime and cefotaxime. It did not inhibit Pseudomonas
      aeruginosa and other Pseudomonas spp., Enterobacter spp., Serratia marcescens or
      Bacteroides fragilis. RU29246 was not hydrolyzed by TEM-1, Staphylococcus aureus
      TEM-2 or Moraxella catarrhalis beta-lactamases, but was hydrolyzed by TEM-3 and
      the chromosomal beta-lactamases of Proteus vulgaris and Morganella morganii.
      Plasmid and chromosomal beta-lactamases were inhibited by RU29246.

PMID- 1396780
TI  - Prevalence of hepatitis A, B and C in Turkey.

PMID- 1396781
TI  - An anatomical filter for exposure equalization in mammography.
AB  - An anatomical filter has been designed, tested and subsequently used in clinical
      practice to equalize optical density over the entire mammographic image, thus
      eliminating the need for dual exposure whenever both the mammary gland and the
      peripheral structures of the breast must be clearly visualized. The use of the
      filter results in a reduction of the optical density, at the peripheral
      structures of the breast, with a simultaneous increase of the contrast, without
      causing deterioration of the mammary gland image. Improved visualization of the
      connective tissue, the skin, the nipple and the subcutaneous adipose tissue is
      achieved, as well as minimization of the radiation dose to the breast for
      patients with an indication of peripheral breast lesions.

PMID- 1396782
TI  - Radial scars detected mammographically in a breast cancer screening programme.
AB  - Radial scars are getting more and more common since the implementation of
      mammography as a diagnostic tool in screening women for breast cancer. At the
      Karolinska Hospital, 18,987 asymptomatic women, between the ages of 50 and 69,
      were screened for breast cancer by means of mammography during the period August
      1989 to May 1991. A total of 735 (3.87%) women were recalled for additional views
      after initial mammograms and 463 (2.44%) were assessed with the help of cytology.
      In all 175 (0.92%) women were selected for surgery and 146 (0.77%) had
      histologically verified cancers. The remaining 29 (0.15%) had non-malignant
      lesions of which 11 (0.06%) were radial scars. All radial scars were diagnosed on
      mammograms and later confirmed with histology. The radiologic characteristics
      were found to be (a) rather thick and long radiating structures accompanied by
      radiolucent linear structures parallel to some of the spicules, (b) absence of
      calcifications, (c) radiolucent areas in the central body of the lesion, (d) an
      average mean size of 6 mm and (e) changing image in different views. Most of the
      lesions, 73% (8/11), were in moderately dense breasts and there was no specific
      relation to the right or left breast. A majority of radial scars, 64% (7/11),
      were found in the upper outer quadrants, 27% (3/11) in the lower outer quadrants
      and 9% (1/11) in the lower inner quadrant. Literature shows that histology uses
      many synonyms for radial scars and therefore team work between the radiologists
      and pathologists is suggested for better conformity of the diagnosis.

PMID- 1396783
TI  - Talocalcaneal coalition: computed tomography and magnetic resonance imaging
      diagnosis.
AB  - A correct evaluation of site and extension of the talocalcaneal coalition
      inducing biomechanical ankle alterations is very important for planning therapy.
      Four male patients were submitted to computed tomography (CT) and three of them
      were also examined by means of magnetic resonance imaging (MRI). In one patient,
      studied by CT only, a bilateral talocalcaneal coalition was present, while the
      other three patients, controlled with CT and MRI, were affected by monolateral
      talocalcaneal coalition which was of osseous type in one case and
      fibrocartilaginous in two cases. CT and MRI provided detailed information on type
      and extension of the coalition and both helped in distinguishing between osseous
      and fibrocartilaginous forms. Only MRI showed an area of subchondral ischemic
      disease of the posterior subtalar joint in one patient with monolateral
      fibrocartilaginous talocalcaneal coalition. Compared with CT, MRI proved to be
      more accurate in evaluation of the talocalcaneal coalition, due to its wider
      display capability.

PMID- 1396784
TI  - Follow-up study of renal transplants by duplex Doppler and gray-scale ultrasound.
AB  - In the early postoperative period after renal transplantation 388 follow-up
      ultrasound examinations were performed in 77 patients. Over a period of 18 months
      standardized duplex indices (resistive index, pulsatility index) and gray-scale
      parameters (parenchyma/sinus index; medulla/cortex index) were sampled. These
      data were correlated retrospectively with clinical and pathological diagnoses. To
      delineate the individual course of duplex and gray-scale indices during different
      transplant diseases we created a new parameter: the MID (maximal index
      difference) which is a result of the difference between the highest index during
      the phase of renal dysfunction and the lowest index during the phase of normal
      renal function. This MID, calculated for duplex indices and for the
      parenchyma/sinus index, indicated significant differences in the behavior of
      renal transplants during the four main diseases: interstitial rejection, vascular
      rejection, acute tubular necrosis and Cyclosporine A nephrotoxicity. Using the
      MIDs, a table of cut-off values was established, which enables to differentiate
      retrospectively these four transplant complications with a sensitivity of 84% and
      specificity of 81%. In our opinion consequent follow-up examinations with duplex
      and gray-scale sonography should be performed, enabling sonography to become a
      helpful diagnostic instrument in the monitoring of renal transplants.

PMID- 1396785
TI  - Duplex ultrasound diagnosis of symptomatic proximal deep vein thrombosis of lower
      limbs.
AB  - Real time ultrasound (US) was used to examine 165 consecutive inpatients with
      clinically suspected deep vein thrombosis of lower limbs. In order to evaluate
      accuracy, the results of non-invasive techniques were compared with ascending
      venography, performed in all patients. Assessment included only femoro-popliteal
      veins, because of difficulty in visualizing calf vein with US. Diagnosis of
      thrombosis was based on noncompressibility of the examined veins; pulsed Doppler
      provided further information by evaluating blood flow. In our series Duplex
      ultrasound was very accurate in detecting acute thrombosis of the proximal veins,
      sensitivity being 97% and specificity 98%. With US it is also possible to detect
      conditions that mimic deep vein thrombosis, such as muscular rupture, hematoma,
      popliteal cyst or compressive tumors. In conclusion US is considered a valid
      alternative to contrast venography in the diagnosis of proximal vein thrombosis
      of lower limbs.

PMID- 1396786
TI  - Color Doppler imaging of the right gastroepiploic artery as an in situ coronary
      artery bypass graft.
AB  - In recent years the right gastroepiploic artery (GEA) has been used as an in situ
      graft in coronary artery bypass grafting (CABG). The specific anatomical course
      of the GEA graft enables the use of color Doppler imaging technique to evaluate
      its patency. The results in 21 patients demonstrate the efficiency of this
      technique; postoperative angiography to establish patency can therefore be
      avoided.

PMID- 1396787
TI  - Intrapericardial bronchogenic cyst: CT and MR demonstration.

PMID- 1396788
TI  - Computed tomographic staging of esophageal carcinoma: a study on interobserver
      variation and correlation with pathological findings.
AB  - Despite numerous reports on the efficacy of CT in the staging of esophageal
      carcinoma, no data are available on the reproducibility of the procedure. Three
      experienced radiologists independently reviewed the CT scans of 35 patients
      retrospectively. Calculation of interobserver variation was performed using the
      kappa statistic. The CT findings of each observer were subsequently correlated
      with the surgical and pathological findings of 17 patients. There was a large
      interobserver variation concerning involvement of the aorta, pulmonary vessels,
      vertebral column, stomach and lymph nodes, ranging from poor to excellent
      agreement. Agreement between observers on extension of the disease to the
      tracheobronchial tree, pericardium and liver was good or excellent. Agreement
      between the CT findings of all observers and the surgical findings for invasive
      growth was poor. CT pathological correlation of the three observers showed
      sensitivities ranging from 50 to 57%, specificities ranging from 50 to 60% and
      accuracies ranging from 46 to 71%. It can be concluded from this study that
      patients with positive CT findings for involvement of the tracheobronchial tree,
      the pericardium and the liver should be considered unresectable for cure.
      Negative findings, however, should be interpreted with caution, because
      involvement of other structures may still be present. Despite optimistic reports
      on the efficacy of CT in the pretherapy staging of esophageal neoplasms, this
      modality has its limitations.

PMID- 1396789
TI  - Flushable stent-system for internal drainage in occlusive jaundice.
AB  - The effectiveness of biliary stents may be reduced as a result of obstruction by
      tumor material, bile salts or detritus. To circumvent this problem we developed a
      prosthesis system, which allows flushing and repetitive radiological control via
      a subcutaneous port. Prostheses were implanted in 26 patients presenting with
      inoperable occlusive lesions of the bile duct. Patency was regularly monitored by
      checking the bilirubin and alkaline phosphatase levels and using port
      cholangiography. Catheter function was easily maintained in 92% of the patients
      and ended upon malignancy related death. In case of dysfunction, drainage could
      generally be restored with intensive flushing. This new flushable stent-system
      was easily implantable, could be exchanged without renewed percutaneous
      transhepatic puncture and allowed flushing, external drainage, bile probes for
      bacteriological examinations and follow up cholangiography via the subcutaneous
      placed port.

PMID- 1396790
TI  - Pneumocephalus as a complication of nasopharyngeal cannulation.

PMID- 1396791
TI  - Giant aneurysm of the posterior cerebral artery in a one-year-old child.

PMID- 1396792
TI  - Transbrachial approach for aortic and selective supraaortic vessel
      catheterization using a safe and easy technique to reform the Simmons II catheter
      tip.
AB  - A total of 286 patients (158 outpatients) were examined by intra-arterial DSA in
      the evaluation of cerebrovascular disease using a transbrachial approach. In all
      cases a 5F introducer sheath, a 5F pigtail catheter for aortic arch injection and
      a 5F Simmons II catheter for selective catheterization were used. Excellent
      demonstration of aortic arch and supraaortic arteries (including intracranial
      circulation) was obtained (92.2-100%). The complication rate was favorable, with
      only one major complication (thrombosis of an axillary artery). The use of an
      introducer sheath minimizes local complications and vessel wall damage during
      catheter exchange. Aortic arch injection must always be performed prior to
      selective catheterization. The results of selective catheterization prove the
      suitability of the Simmons II catheter, whose typical shape was easily and safely
      obtained using the configuration of the pigtail catheter and a 180 cm long guide
      wire for catheter exchange. Using the technique as described, the transbrachial
      approach is a safe and easy way for optimal vascular evaluation in
      cerebrovascular disease, especially useful in outpatients.

PMID- 1396793
TI  - Spinal cord ischemia complicating hepatic artery chemoembolization in a patient
      with prior hemihepatectomy.

PMID- 1396794
TI  - Tension mediastinal emphysema: emergency percutaneous drainage with CT guidance.
AB  - Four patients aged 8 to 54 years, under mechanical ventilation, presented with
      sudden tension mediastinal emphysema and exhibited typical clinical symptoms of
      compromised venous return. Diagnosis of tension mediastinal emphysema was
      confirmed by CT. A percutaneous catheter with a diameter varying from F12 to F20
      was inserted in the anterior mediastinal compartment with CT control and
      connected to a waterseal aspiration. Emergency treatment was efficient in all
      patients. Percutaneous aspiration was continued for 3 to 20 days.

PMID- 1396795
TI  - Neuroradiologic abnormalities in Marchiafava-Bignami disease of benign evolution.
AB  - Marchiafava-Bignami disease has been recognized since 1903, but only recently has
      it become possible to achieve a probable diagnosis before death occurs. Imaging
      of the central nervous system with MR and CT have contributed significantly to
      such a diagnosis. Two cases of the disease are reported in patients, aged 33 and
      59 years, with benign evolution of neurologic symptoms the diagnosis was
      confirmed by neurologic imaging with MR and CT and both were studied with evoked
      responses. Reversibility of the disease and possible prognostic indicators in
      these and other patients reported in the literature are discussed. The important
      role that diagnostic procedures, especially MR imaging, play in the management of
      this disease is emphasized.

PMID- 1396796
TI  - Comparative trial of Omnipaque 350 (iohexol) and Telebrix 350 (sodium-meglumine
      ioxithalamate) in left ventriculography and coronary arteriography.
AB  - In a double-blind randomized trial, the hemodynamic and electrophysiologic
      effects of the low-osmolar nonionic contrast medium iohexol (Omnipaque) and the
      standard high-osmolar ionic monomer sodium-meglumine-ioxithalamate (Telebrix) at
      left ventricular angiography and selective coronary arteriography were evaluated.
      Sixty patients were divided into two groups of 30 patients; one group received
      Omnipaque in a dosage of 350 mgI/ml and the other group received Telebrix in a
      dosage of 350 mgI/ml. The Omnipaque showed significantly less effects on heart
      rate and myocardial contractility, and induced less electrophysiological changes
      than did Telebrix. However, there was a significant increase of 10% in the
      diameter of the left coronary artery following selective coronary injection with
      Telebrix, while Omnipaque induced practically no change in vessel diameter. All
      hemodynamic and electrophysiologic effects proved to be short-lasting. We
      conclude that ionic and nonionic agents are similarly efficacious in providing
      adequate images with minimal risk to the patient. However, the nonionic agents
      exert slightly more alterations in cardiac hemodynamics and in
      electrocardiographic intervals. The vasodilatory effect on coronary artery
      diameter by Telebrix may entail a more rapid clearance of contrast medium from
      the coronary circulation, which might be of some advantage over nonionic contrast
      media.

PMID- 1396797
TI  - High-resolution MR imaging of the inner ear: findings in Meniere's disease.
AB  - Symptoms in Meniere's disease are characterized by hydrops of the endolymphatic
      system with recurrent rupture of the membranous labyrinth. The primary cause of
      the increased endolymphatic volume appears to be an imbalance between secretion
      and resorption of the endolymph which may be due to an obstruction of the
      membranous endolymphatic duct and sac, located in the vestibular aqueduct. The
      membranous endolymphatic duct and sac are not expected to be visualized using
      conventional tomography and high-resolution computed tomography (HR-CT), whereas,
      these are identified with high resolution MRI (HR-MRI). By HR-MRI, we proposed to
      demonstrate morphological alternation in 12 patients with Meniere's disease, this
      group was compared with a group of 20 healthy subjects. The degree of
      visualization on HR-MRI of the membranous endolymphatic duct and sac running
      through the vestibular aqueduct in the bony canal was assessed. There was a
      distinct decrease in visualization of the membranous endolymphatic duct and sac
      in the Meniere's group. The results confirm the value of the HR-MRI technique to
      identify an anatomical abnormality, which is directly correlated with the lesion
      in cases of unilateral Meniere's disease.

PMID- 1396799
TI  - The sympathetic system in evolution and in ischaemic heart disease--a
      controversy?

PMID- 1396798
TI  - Computed tomography and magnetic resonance imaging in the preoperative work-up
      for cochlear implantation.
AB  - The role of CT and MRI in the evaluation of patients for possible insertion of a
      multichannel intracochlear hearing device was appraised. The study included 52
      patients who underwent both CT and MRI examinations, 40 of whom were later
      operated on. Coronal and axial T2-weighted spin-echo sequences were performed in
      25 volunteers with normal hearing and in 47 adult patients. In 5 patients,
      instead of a T2-weighted spin-echo sequence, a T2*-weighted gradient echo 3D
      sequence with axial presaturation was used. In 39 patients with normal
      appearances on CT and MRI, the implant device was successfully inserted. One
      patient who underwent surgery had a reduced cochlear signal on MRI but a normal
      CT scan; however, at surgery, the implant device could only be inserted into the
      first turn of the cochlea, due to fibrous obliteration. In 3 of 12 patients who
      were not operated upon, the results of diagnostic imaging indicated that the
      insertion of an intracochlear hearing device was not useful. Our experience
      indicates that, with reduced cochlear fluid signal intensities on MRI, fibrous
      obliteration of the cochlear turns is likely to be present. MRI proved to be a
      useful adjunct to CT, but the latter was necessary for the evaluation of bony
      abnormalities. Gradient echo sequences can successfully replace time-consuming T2
      weighted spin-echo sequences.

PMID- 1396800
TI  - Guidelines for the use of implantable cardioverter defibrillators. A Task Force
      of the Working Groups on Cardiac Arrhythmias and Cardiac Pacing of the European
      Society of Cardiology.

PMID- 1396801
TI  - Family history as an independent risk factor of coronary artery disease.
AB  - The relationship between family history of ischaemic heart disease and the
      presence of coronary heart disease was studied in 387 patients undergoing routine
      coronary arteriography prior to valve replacement. One hundred and seven patients
      (27.6%) had a family history of ischaemic heart disease. Of these, 52 (48.6%) had
      significant coronary artery disease compared with 60 of 280 (21.4%) patients
      without a family history (P < 0.001). The overall severity (coronary score) and
      extent (number of vessels) of coronary artery disease was greater in those
      patients with a family history (P < 0.001). Moreover, the incidence of
      significant coronary disease increases as the number of relatives with ischaemic
      heart disease also increase (P < 0.001). Multiple logistic regression analysis
      suggests that family history is an independent predictor of the presence of
      significant coronary artery disease.

PMID- 1396802
TI  - Exercise-induced QRS changes in healthy men and women: a multivariate analysis on
      their relation to background data and exercise performance.
AB  - Changes in the QRS segment during exercise have repeatedly been suggested to
      provide diagnostic information with respect to ischaemic heart disease, but the
      subject is controversial. In order to study the possibly confounding effects of
      gender, age, resting ECG and exercise performance, 50 healthy subjects were
      investigated with computerized vectorcardiography during a maximal ergometer
      exercise test. The overall change in the QRS complex decreased significantly with
      age and female gender (P < 0.001). However, these responses were better explained
      by baseline QRS size, change in heart rate and systolic blood pressure (adjusted
      r2 > 0.70, vs adjusted r2 > 0.41). Effects of age were seen in the Y-lead, and
      gender effects in the X- and Z-leads (P < 0.0001). In multivariate analyses, X-
      and Y-lead alterations correlated negatively to change in heart rate and resting
      QRS size (X-lead; adjusted r2 > 0.50, Y-lead; r2 > 0.44). Z-lead alterations
      correlated negatively with female gender and resting Z-lead QRS size (adjusted r2
      > 0.31). ST changes correlated with QRS changes in the X- and Y-leads (P < 0.05).
      QRS changes immediately after exercise correlated with alterations during
      exercise (P < 0.004), maximal load (P < 0.01) and time to hypotension post
      exercise (X- and Z-lead; P < 0.02). In conclusion, QRS changes appear to be
      related to baseline QRS size, change in heart rate and ST change, factors which
      may have important confounding effects. Consideration of these factors may help
      in resolving the controversy surrounding QRS changes.

PMID- 1396803
TI  - Paradoxical early lengthening and subsequent linear shortening of the QT interval
      in response to exercise.
AB  - The QT responses to exercise during ventricular pacing were evaluated in 12
      patients in whom permanent pacemakers were implanted for complete heart block.
      The initial response of the QT to exercise was a paradoxical lengthening during
      the first minute of exercise (mean 4.8 ms P < 0.01). Thereafter, the QT was found
      to shorten in a linear fashion in response to increasing exercise, both in terms
      of exercise duration (r = 0.787; P < 0.001) and atrial rate (r = 0.712; P <
      0.001). The total QT shortening with exercise was small (20 ms for a mean
      increase in atrial rate of 60 beats.min-1) and displayed substantial inter
      individual variability (9-31 ms). These results explain some of the limitations
      of the QT pacemaker, and provide insights in to the dynamics of the QT response,
      which may help tailor the programming of these systems to the individual patient.

PMID- 1396804
TI  - Catheter ablation of free wall accessory atrioventricular pathways in 89 patients
      with Wolff-Parkinson-White syndrome--comparison of direct current and
      radiofrequency ablation.
AB  - To evaluate and compare the safety and efficacy of catheter-mediated direct
      current (DC) or radiofrequency (RF) ablation in patients with free wall accessory
      atrioventricular pathways, 89 patients with free wall accessory atrioventricular
      pathway (AP)-mediated tachyarrhythmias underwent catheter ablation.
      Electrophysiological parameters were similar in the patients with DC (group I, 29
      patients with 30 APs) or RF (group II, 60 patients with 64 APs) ablation.
      Immediately after ablation, it was seen that 27 of 30 APs (90%) had been ablated
      successfully with DC, but two of the 27 APs had early return of conduction and
      received a second ablation session; three of eight APs (38%) and 53 of 56 APs
      (95%) were ablated successfully with RF through a small-tip (2 mm) and a large
      tip (4 mm) electrode catheter, respectively. Seven of the eight APs who had a
      failed RF ablation later had a successful DC ablation. During the follow-up
      (group I, 14 to 27; group II, 8 to 14 months), all successfully ablated patients
      had no recurrence of tachycardia. Complications in DC ablation included transient
      hypotension (two patients), and pulmonary air-trapping (two patients); in RF
      ablation the complications included cardiac tamponade (1 patient) and suspicious
      aortic dissection (1 patient); myocardial injury (reflected by peak CK-MB, 34 +/-
      5 vs 15 +/- 4 IU.l-1) and pro-arrhythmic effects (new atrial and ventricular
      arrhythmias) were more severe in those who had DC ablation. Procedure and
      radiation exposure time were significantly longer in RF ablation (DC, 3.6 +/- 0.2
      h, 34 +/- 4 min; RF 4.0 +/- 0.4 h, 46 +/- 10 min). This study confirms that RF
      ablation with a large-tip electrode catheter is an effective and relatively safe
      non-surgical method for treatment of free wall accessory atrioventricular pathway
      mediated tachyarrhythmias.

PMID- 1396805
TI  - Too early for cardiac transplantation--the right decision?
AB  - In 109 out of 479 patients who were referred for cardiac transplantation it was
      considered to be too early to put them on the waiting list for a donor heart. The
      clinical course of these 109 patients was analysed in order to verify whether
      this decision had been right. The mean age of the patients was 43 years, half of
      them suffered from ischaemic heart disease. The systolic left ventricular
      function of the patients was severely depressed (mean left ventricular ejection
      fraction 21%) and the left ventricular cavity was markedly dilated (mean
      echocardiographic end diastolic dimension 73 mm). Functional capacity, measured
      by bicycle ergometry, was low: mean maximal workload 62% of the expected load for
      gender, height and age. The median follow-up duration was 31 months. The survival
      rate of the patients was better than that of 175 patients who were accepted for
      transplantation after referral, 92%, 87%, 81%, 71% and 73%, 73%, 71%, 68% after
      1, 2, 3 and 4 years respectively. Re-assessment was necessary in 29% of the
      patients within 1 year and in 52% within 3 years. Twenty patients died: 12
      patients died before re-assessment had been initiated (eight sudden deaths), six
      patients because of progressive heart failure before heart transplantation could
      be performed and two patients died after heart transplantation. Left ventricular
      ejection fraction, pulmonary capillary wedge pressure and transpulmonary gradient
      were not reliable predictors of the course of the patients.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1396806
TI  - Open heart surgery in Europe 1990.

PMID- 1396807
TI  - Usefulness of dipyridamole-echocardiographic test to identify jeopardized
      myocardium after thrombolysis. Limited clinical predictivity of dipyridamole
      echocardiographic test in convalescing acute myocardial infarction: correlation
      with coronary angiography.
AB  - A dipyridamole-echocardiographic test (DET) was carried out to find out how safe
      and useful it was in predicting clinical outcome and in identifying patients at
      risk. The test was performed in 107 asymptomatic patients early (5 to 8 days)
      after a first acute uncomplicated myocardial infarction managed with thrombolytic
      therapy. All patients were followed up for a mean of 15 months and 94 underwent
      coronary angiography. The test was considered positive if transient asynergy of
      contraction was newly detected either in the infarct and adjacent areas or in the
      remote zones; two subsets were studied, according to the dose of dipyridamole
      (0.56 or 0.84 mg.kg-1) needed to induce ischaemia. The test was accomplished
      satisfactorily in 96% of patients. Intra-inter-observer agreements were 88% and
      91% respectively. The test also proved safe at the high infusion dose. During the
      follow-up period, two patients died, one experienced re-infarction and 12 (12%)
      developed recurrence of angina. DET was abnormal in 32 patients (adjacent and
      remote asynergy in 28 and four patients respectively): 18 had a critical and two
      a non-critical stenosis in the infarct-related vessel, and nine had an occluded
      artery with collateral distal flow. Multivessel disease was present in 11
      patients considered positive, four in the remote and seven in the adjacent zones.
      However, 20 patients with negative DET results had multivessel disease. Of the
      positive DET patients, seven had angina. There were eight total events in the 71
      negative DET patients, five of whom had multivessel disease. Abnormality was more
      pronounced in positive DET patients, but did not influence the outcome.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396808
TI  - Pharmacological stress echocardiography in the diagnosis of coronary artery
      disease and myocardial ischaemia: a comparison between dobutamine and
      dipyridamole.
AB  - The objective of this study was to relate regional wall motion abnormalities
      assessed by dobutamine and dipyridamole stress echocardiography to quantitative
      measurements of coronary artery stenoses in consecutive patients referred for
      coronary angiography, and to compare haemodynamic effects of and complications
      related to the two agents. Patients underwent stress echoes on separate days in
      random sequence and had coronary angiography within 3 days of stress
      echocardiography. Echocardiograms were assessed by two investigators unaware of
      the patients' coronary anatomy. Coronary angiograms were also assessed
      quantitatively using the computer-assisted Cardiovascular Angiography Analysis
      System. There were 46 consecutive patients referred for coronary angiography; 28
      were using beta-antagonists. Main outcome measures were sensitivity and
      specificity for dobutamine and dipyridamole stress echocardiography for detection
      of coronary artery disease (wall motion abnormalities at rest or stress) and
      myocardial ischaemia (stress induced new wall motion abnormalities). Sensitivity
      for the detection of myocardial ischaemia was found to be 57% for dobutamine and
      64% for dipyridamole. Specificities were 78% and 89% respectively. Sensitivities
      for detection of coronary artery disease (lesion > or = 50% diameter stenosis)
      was 79% for dobutamine and 82% for dipyridamole; specificities were 78% and 89%
      respectively. These differences between the two agents are not significant. There
      were no severe side effects with either agent. Mean heart rate rose significantly
      with both tests but was higher with dobutamine; mean systolic blood pressure rose
      with dobutamine and fell with dipyridamole. It was concluded that dobutamine and
      dipyridamole stress echocardiography have similar sensitivities and specificities
      for detection of myocardial ischaemia and coronary artery disease although the
      haemodynamic effects of the two agents are different. Both are free from serious
      complications.

PMID- 1396809
TI  - The use of an exponential protocol for bicycle and treadmill exercise testing in
      patients with chronic cardiac failure.
AB  - We have studied a standardized exercise protocol suitable for use with a
      treadmill or bicycle (STEEP protocol) and compared it with a modified Bruce
      treadmill protocol in a group of patients with chronic cardiac failure. The STEEP
      protocol has been previously validated in normal subjects. Exercise time (6.79 +/
      2.42 vs 5.34 +/- 1.95 min, P < 0.05) and peak VO2 (16.66 +/- 4.09 vs 15.01 +/-
      3.72 ml.min-1.kg-1, P < 0.05) were greater with the STEEP treadmill compared with
      the bicycle protocol, but VO2 was very similar at equal exercise stages in both
      modalities. Heart rate and respiratory exchange ratio tended to be greater during
      bicycle exercise at equal stages. Exercise time was greater with the modified
      Bruce protocol (9.00 +/- 3.02 min, P < 0.05) than with either STEEP protocol, but
      peak VO2 (17.13 +/- 4.52 ml.min-1.kg-1) was similar to that obtained with the
      STEEP treadmill test. We conclude that the STEEP protocol may be used to test
      patients with chronic cardiac failure, and that exercise times relate well in
      both treadmill and bicycle. The protocol should prove useful in studies involving
      a wide range of exercise capacities or both bicycle and treadmill exercise.

PMID- 1396810
TI  - Cardiac involvement in thalassaemia major: altered atrial natriuretic peptide
      levels in asymptomatic patients.
AB  - Congestive heart failure is the most common cause of death in young adults with
      thalassaemia major. In the present study we compared atrial natriuretic peptide
      levels (ANP) in 30 asymptomatic patients with thalassaemia major (aged 16.6 +/-
      6.4 years), normal left ventricular diastolic cavity dimension and systolic
      function, with 30 aged and sex matched normal control subjects. ANP levels were
      significantly higher in patients with thalassaemia major compared to controls
      (93.9 +/- 26.3 pg.ml-1 vs 51.8 +/- 26.5 pg.ml-1; P < 0.001). Plasmatic renin
      activity, aldosterone, urinary sodium and catecholamine levels at basal
      conditions did not differ significantly in these two groups (ns). Blood volume
      stimulation (blood transfusion) in thalassaemic patients was followed by an
      increase of mean ANP values (93.9 +/- 26.3 to 109.1 +/- 40.5 pg.ml-1; P < 0.03).
      ANP basal levels above two standard deviations of the mean values obtained in
      normal control subjects were considered as abnormal and found to be in close
      correlation with the presence of diastolic dysfunction of the left ventricle
      identified by Doppler echocardiography. The method has a 57% sensitivity and a
      91% specificity for revealing pre-clinical cardiac involvement (P < 0.02).
      Although a longer observation period is necessary in order to define the clinical
      and prognostic significance of these data, our results show that an increase in
      ANP basal values is present in asymptomatic patients with thalassaemia major.
      This suggests initial myocardial involvement, while ANP response to volume
      overload is maintained.

PMID- 1396811
TI  - Automated versus observer blood pressure as determinants of left ventricular
      structure.
AB  - We studied the contribution of automated blood pressure measurements to the
      variation in left ventricular structural characteristics, independent of pressure
      measured by an observer. Thirty eight patients referred for hypertension
      underwent 24 h blood pressure monitoring. Echocardiography and repeated blood
      pressure measurements were taken on 2 different days by an observer and by the
      use of the Dinamap 845 device. Blood pressure by the observer averaged 157/101
      mmHg, Dinamap pressure 152/94 mmHg, 24 h pressure 137/92 mmHg, left ventricular
      mass 218 g and mean wall thickness 12.7 mm. Left ventricular mass and wall
      thickness were related (P < 0.05) to systolic observer (r = +0.46; r = +0.47),
      Dinamap (r = +0.42; r = +0.41) and 24 h blood pressure (r = +0.46; r = +0.53);
      the correlation coefficients were lower (r = +0.35 to +0.51; P < 0.05) for
      diastolic pressure. These relations were independent of age, gender, height,
      weight and heart rate. The Dinamap pressure did not contribute to the difference
      in the left ventricular structural characteristics, independent of the observer
      pressure. The 24 h ambulatory pressure explained a small but significant (P <
      0.05) fraction of the variation in mean wall thickness in addition to the
      observer pressure. Left ventricular mass and mean wall thickness were not related
      to the day-night difference in blood pressure (P > 0.25). In conclusion,
      observer, Dinamap and ambulatory pressures are significantly related to cardiac
      structural variables. Ambulatory pressure, but not Dinamap pressure, explains a
      small part of wall thickness variance in addition to well-standardized pressure
      measured by an observer.

PMID- 1396812
TI  - Effects of impaired lung function and pulmonary regurgitation on maximal exercise
      capacity in patients with repaired tetralogy of Fallot.
AB  - Long-term haemodynamic results and exercise capacity were studied in 34 patients
      with tetralogy of Fallot (24 men and 10 women) repaired 10.0 +/- 4.9 (mean +/-
      SD) years previously and compared to 34 healthy matched controls. All subjects
      were studied by resting spirometry, echocardiography and a symptom limited
      treadmill exercise test (modified Bruce protocol). The maximal oxygen consumption
      was 38.2 +/- 8.0 ml.kg-1.min-1 in patients and 48.1 +/- 8.1 ml.kg-1.min-1 in the
      control group (P < 0.001). Reduced maximal oxygen consumption was found in
      patients with low vital capacity (VC) and pulmonary regurgitation (PR). The
      ventilatory anaerobic threshold (VAT) was 23.8 +/- 0.6 ml.kg-1.min-1 and 29.9 +/-
      0.6 ml.kg-1.min-1 in patients and controls, respectively (P < 0.001). VC was 3.4
      +/- 1.21 in patients and 4.0 +/- 1.31 in controls (P < 0.02). In the patients,
      maximal ventilation was reduced and at submaximal exercise, the breathing
      frequency increased. Heart rates during exercise were similar in patients and
      controls. Tricuspid regurgitation (TR) was detected in 20 patients (58.8%);
      however, the exercise capacity was not reduced. Thus, impaired exercise capacity
      in tetralogy of Fallot is partly due to reduced resting lung function, pulmonary
      regurgitation and low ventilatory anaerobic threshold.

PMID- 1396813
TI  - Increased CKMB (mass concentration) in patients without traditional evidence of
      acute myocardial infarction. A risk indicator of coronary death.
AB  - A study of 102 patients consecutively admitted to a coronary care unit (CCU)
      investigated the clinical usefulness of three different immunoenzymometrical CKMB
      methods: NovoClone CK-MB, ICON QSR CKMB and IMx CK-MB. Blood samples were drawn
      on admission and then every 6 h for 48 h. The three different methods correlated
      very well (r = 0.93-0.96). With discrimination levels of 10 micrograms.l-1 for
      NovoClone CK-MB and 5 micrograms.l-1 for the other two methods, a sensitivity of
      1.0 and a still acceptable specificity (> 0.81) were achieved. In the group of
      patients (n = 53) with suspicion of acute myocardial infarction (AMI) but with no
      standard criteria for AMI, 14 patients were identified with small but significant
      increase of serum CKMB (mass concentration) and an increased CKMB (mass
      concentration)/CK ratio. During a 4 year follow-up nine out of these 14 patients
      died within 2 years, the majority being coronary deaths, as compared to only two
      out of the remaining 39 non-AMI patients with suspicion of AMI but with normal
      CKMB values (chi 2 = 18.47, P < 0.001). The finding of such a high mortality rate
      among patients with increased CKMB (mass concentration) has an important
      prognostic value even in patients without standard criteria for AMI.

PMID- 1396814
TI  - Cardiomyopathy in Friedreich's ataxia: a Doppler-echocardiographic study.
AB  - Heart involvement is frequent in Friedreich's ataxia (FA), the most prevalent of
      the spino-cerebellar degenerative diseases, which is inherited with an autosomal
      recessive pattern. However, the pathophysiological link between cardiac and
      neurological disorders is not yet clearly established. We compared a group of 10
      patients with FA to a control group (C) of 16 normal subjects, using Doppler
      echocardiography. To see whether cardiac involvement was specific to FA, the data
      of patients with FA were also compared to those of patients with autosomal
      dominant olivo-ponto-cerebellar atrophia (OPCA), another spino-cerebellar
      degenerative disease. There was an increase in left ventricular mass index in FA
      (154 +/- 9 g.m-2 vs 99 +/- 7 g. m-2 in C, P < 0.001), systolic function was
      normal, the ejection fraction (EF) slope and E/A ratio were decreased (85 +/- 9
      mm.s-1 vs 130 +/- 7 mm.s-1 in C, P < 0.001 and 1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P
      < 0.01, respectively), while the isovolumic relaxation period was increased (96
      +/- 3 ms vs 92 +/- 2 ms in C, P < 0.01). Deceleration time and time-velocity
      integrals of A wave to total mitral flow were not modified. In OPCA only the E/A
      ratio was decreased (1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.05). These data show
      the presence of cardiomyopathy in FA with left ventricular hypertrophy and
      suggest the presence of diastolic function abnormalities. The cardiomyopathy
      seems specifically associated with FA and not to spino-cerebellar degenerative
      disease in general.

PMID- 1396815
TI  - Regulatory peptides in the plasma of patients with chronic cardiac failure at
      rest and during exercise.
AB  - The levels of several regulatory peptides were measured in peripheral plasma
      samples from individuals with chronic cardiac failure (CCF) and matched controls
      in both the resting state and during a short period of maximal exercise. Basal
      levels of noradrenaline (NA; 705 +/- 114 vs 195 +/- 54 ng.l-1; mean +/- SEM; P <
      0.05), plasma renin activity (PRA; 12.9 +/- 2.9 vs 2.1 +/- 0.3 ng AI ml-1.h-1; P
      < 0.05) and aldosterone (ALDO; 325 +/- 49 vs 87 +/- 8 ng.l-1; P < 0.05) were all
      raised in the patients with CCF, and increased further with exercise. Basal
      circulating levels of atrial natriuretic peptide (ANP) were also significantly
      higher in the CCF group compared to controls (136 +/- 35 vs 27 +/- 5 ng.l-1; P <
      0.01), but the response to exercise was attenuated, so that at peak exercise, no
      significant difference was observed. Basal circulating levels of gastrin
      releasing peptide (GRP) (29 +/- 4 vs 40 +/- 4 ng.l-1; P < 0.05) and secretin (13
      +/- 1 vs 32 +/- 4 ng.l-1; P < 0.05) were significantly lower in the CCF group
      when compared to controls and there was no significant change in the levels of
      either peptide with exercise. Levels of neurokinin A (NKA), neuropeptide Y (NPY)
      and neurotensin (NT) were somewhat higher in patients, but the differences were
      not significant, and there were no changes during exercise. There were also no
      significant differences in the levels of vasoactive intestinal peptide (VIP),
      glucose-dependent insulinotropic polypeptide (GIP), insulin or glucagon in either
      experimental group both before and during exercise. We have therefore identified
      different circulating levels of certain regulatory peptides in patients with CCF,
      but the significance of these remains unclear.

PMID- 1396816
TI  - Lp(a) levels in patients undergoing aorto-coronary bypass surgery.
AB  - The aims of this study were to evaluate plasma lipid, apoprotein and Lp(a) levels
      in patients with severe coronary atherosclerosis undergoing aorto-coronary bypass
      surgery (BP) and to relate these parameters to the involvement of one or more
      vessels. Seventy-seven male patients and 77 cardiovascular disease-free controls,
      matched for sex, age and body weight were studied. Higher triglyceride and apo B
      levels with lower HDL-cholesterol and apo A-I levels were found in BP patients in
      comparison with the controls. Lp(a) levels were slightly, but not significantly,
      increased. Moreover BP patients presented a significantly higher prevalence of
      HDL-cholesterol levels below 35 mg dl-1 (49.3% vs 22.1%) and Lp(a) levels above
      70 mg dl-1 (10.4% vs 1.3%) than the controls. When patients were divided
      according to the number of coronary vessels involved (one, two or three), no
      significant difference was found, with a trend to increase in Lp(a) mean levels
      and in prevalence of Lp(a) levels above 30 and 70 mg dl-1 in more severely
      diseased patients. These results suggest that patients with severe coronary
      artery disease undergoing aorto-coronary bypass surgery show low HDL-cholesterol
      levels with high triglyceride levels. Moreover Lp(a) levels above 70 mg dl-1 are
      highly associated with severe coronary vessel stenosis.

PMID- 1396817
TI  - Atrial automatic tachycardia in infancy and childhood.
AB  - Twenty-one cases (13 male, eight female) of atrial automatic tachycardia (AAT)
      assessed by standard and Holter-ECG in otherwise healthy infants and children
      have been documented. AAT was incessant in 12 patients, repetitive in seven, and
      of undetermined type in the remaining two. The frontal P wave axis suggested an
      ectopic focus in the high right atrium or right atrial appendage in 13 patients,
      in the low right atrium in one patient, and in the left atrium in seven patients.
      Thirteen out of 14 patients with the incessant or undetermined type of AAT were
      symptomatic, in contrast to only two of seven patients with the repetitive type.
      All patients were treated with between one and eight (median three)
      antiarrhythmic drugs. The most effective drug was amiodarone, followed by the
      class I C antiarrhythmic drugs, propafenone and flecainide. At present, all
      patients are alive 4 months to 21 years (median 2.5 years) after diagnosis of
      AAT. Twelve patients are in sinus rhythm, five of them without any medication.
      Nine patients still have AAT, which, however, is repetitive or intermittent in
      all but one. In conclusion, AAT is an unusual, and in its incessant form often
      severely symptomatic arrhythmia, which is resistant to conventional
      antiarrhythmic medication. However, amiodarone and class I C antiarrhythmic drugs
      are frequently effective. Since medical treatment with these drugs is often
      successful, and AAT may resolve completely, a conservative approach is indicated
      in many cases.

PMID- 1396818
TI  - Prolonged cardiac arrest and complete AV block during upright tilt test in young
      patients with syncope of unknown origin--prognostic and therapeutic implications.
AB  - The purpose of this study was to define the history and prognosis of 12 patients
      (8 males, 4 females) with syncope of unknown origin (5 to 15 episodes), who
      developed prolonged asystole or complete AV block during the upright tilt test
      (UTT). The mean age (+/- SD) of the patients was 29 +/- 7.4 years, and all had
      normal neurological and cardiological findings on evaluation. These patients were
      selected from a larger group of 92 cases with positive UTT out of a total of 136
      subjects who were referred for recurrence of syncope. Neither clinical nor
      autonomic nervous system evaluation distinguished these 12 patients from those
      with positive UTT. Following UTT, therapy was initiated and consisted of
      transdermal scopolamine in four, disopyramide in two, and beta-blockers in four
      patients. During follow-up (mean, 17 +/- 5.4 months), four patients had
      recurrences but none experienced episodes of life-threatening syncope. These
      patients do not show an enhanced risk of sudden death, and drug therapy seems to
      improve their clinical course. Only long-term follow-up would correctly identify
      a subgroup at higher risk.

PMID- 1396819
TI  - Chlamydial endocarditis: a report on ten cases.
AB  - Over the period 1983-1990, 10 cases of infective native-valve endocarditis as a
      result of Chlamydia were seen. All patients were men, with a mean age of 42
      years, and none had a history of exposure to Chlamydia psittaci. Symptoms, such
      as weight loss and anorexia, with fever in eight cases, had persisted for at
      least 2 months before admission. Haemodynamic failure was present in seven
      patients, and neurological signs in four. The aortic valve was involved in seven
      cases, the mitral valve in one and both valves in two. Vegetations, often
      fingerlike, were observed by echocardiography in nine cases. All patients
      required valve replacement, and three died in the year following diagnosis. Blood
      cultures were consistently negative in all cases, and no antibiotics had been
      given before admission. Significant titres of complement fixing anti-chlamydial
      antibodies were present in six cases, and micro-immunofluorescence using the
      three chlamydial species showed cross-reacting antibodies in all nine cases
      studied, with transient IgM positivity in six cases. Histologically, the leaflets
      were fibrosed and infiltrated by large macrophages containing dark red granules
      after Machiavello staining. These granules were specifically stained by
      immunofluorescence using monoclonal antibody to Chlamydia common antigen, but not
      by that specific for C. pneumoniae. No organisms were seen after Gram staining,
      and no positive chlamydial immunofluorescence was seen on sections of valves from
      patients with staphylococcal or streptococcal endocarditis.

PMID- 1396820
TI  - The significance of myocardial ischaemia and verapamil treatment on the
      prevalence of supraventricular tachyarrhythmias in patients recovering from acute
      myocardial infarction. Danish Study Group on Verapamil in Myocardial Infarction.
AB  - Twenty-four hour Holter monitoring and symptom-limited exercise testing were
      carried out prior to discharge in 157 patients recovering from acute myocardial
      infarction. Supraventricular arrhythmias (SVT) during Holter monitoring were
      recorded in 15%, and ST segment depression during exercise in 27%. No association
      between exercise-provoked ischaemia and SVT was found in the late hospital phase
      of myocardial infarction. After the tests, patients were double-blindly
      randomized to treatment with verapamil 120 mg t.i.d. or placebo. One month after
      randomization 24 h Holter monitoring was repeated in 125 patients (verapamil =
      63, placebo = 62). At one month a significantly increased incidence of SVT was
      found in the placebo group (25%) compared to the verapamil-treated patients (9%)
      (P = 0.04). The increased prevalence in the placebo group was mainly due to an
      increased incidence of SVT in patients with exercise-induced ischaemia (P =
      0.03). This increment was blurred in the verapamil group. In conclusion, the
      prevalence of SVT increases during the first month after myocardial infarction.
      The increase is most pronounced in patients with residual myocardial ischaemia
      and seemed to be prevented by treatment with verapamil.

PMID- 1396821
TI  - Oxidative metabolism and myocardial blood flow changes after transthoracic DC
      countershocks in dogs.
AB  - Changes in oxidative metabolism and myocardial blood flow were investigated in
      adult greyhounds following transthoracic shocks from a DC cardiac defibrillator
      (400 Joules stored energy, damped sine wave, 0.5 min intervals). Myocardial
      lactate extraction became negative maximally at 1 min, following both two (mean 
      24% +/- SEM24) or five (-193% +/- 148) shocks and returned to baseline by 6-15
      min. Transient reductions were also observed in myocardial extraction of pyruvate
      and free fatty acids but not glucose. Myocardial necrosis assessed at 4 h
      following the shocks was 0.05 g (+/- 0.03) after two shocks, 6.5 g (+/- 1.5)
      after five shocks and zero in controls. Mean peak noradrenaline levels in
      arterial (785 +/- 319 pg.ml-1) and coronary sinus (916 +/- 313 pg.ml-1) blood at
      1 min after five shocks were higher than after 0 shocks (82 +/- 33 pg.ml-1 and
      201 +/- 63 pg.ml-1 respectively), P < 0.05. Great cardiac venous blood flow was
      measured by a thermodilution technique, with continuous infusion of 0.9% saline,
      before, during and after five shocks. Mean blood flow fell from 47 +/- 13 ml.min
      1 to a minimum of 36 +/- 7 ml.min-1 during shocks, and then rose to 83 +/- 17
      ml.min-1 at 2 min after the fifth shock (P < 0.05). Following damaging
      countershocks, oxidative metabolism is depressed, in keeping with a primary
      disturbance of mitochondrial function. These metabolic changes are not secondary
      to ischaemia, since an increase in blood flow in the great cardiac vein (GCV) is
      observed. Vasodilatation of the coronary vascular bed must occur to account for
      this.

PMID- 1396822
TI  - Infective right atrial thrombus: a rare complication of total parenteral
      nutrition in an adult.
AB  - We describe a case of an infective right atrial thrombus, following total
      parenteral nutrition, in a 21-year-old woman undergoing a surgical procedure for
      long-standing chronic ulcerative colitis. She presented with high temperature and
      the illness did not respond to antibiotic therapy. A 2-dimensional echocardiogram
      showed a mobile right atrial mass that at surgery was identified as a thrombus.
      Thrombus cultures grew coagulase-negative Staphylococcus aureus.

PMID- 1396824
TI  - The European ST-T database: standard for evaluating systems for the analysis of
      ST-T changes in ambulatory electrocardiography.
AB  - The project for the development of the European ST-T annotated Database
      originated from a 'Concerted Action' on Ambulatory Monitoring, set up by the
      European Community in 1985. The goal was to prototype an ECG database for
      assessing the quality of ambulatory ECG monitoring (AECG) systems. After the
      'concerted action', the development of the full database was coordinated by the
      Institute of Clinical Physiology of the National Research Council (CNR) in Pisa
      and the Thoraxcenter of Erasmus University in Rotterdam. Thirteen research groups
      from eight countries provided AECG tapes and annotated beat by beat the selected
      2-channel records, each 2 h in duration. ST segment (ST) and T-wave (T) changes
      were identified and their onset, offset and peak beats annotated in addition to
      QRSs, beat types, rhythm and signal quality changes. In 1989, the European
      Society of Cardiology sponsored the remainder of the project. Recently the 90
      records were completed and stored on CD-ROM. The records include 372 ST and 423 T
      changes. In cooperation with the Biomedical Engineering Centre of MIT (developers
      of the MIT-BIH arrhythmia database), the annotation scheme was revised to be
      consistent with both MIT-BIH and American Heart Association formats.

PMID- 1396823
TI  - High-density lipoprotein cholesterol and coronary, cardiovascular and all cause
      mortality among middle-aged Norwegian men and women.
AB  - From 1977 to 1982 screening for cardiovascular disease was performed in three
      Norwegian counties. All those aged between 40 and 54 years were invited, of whom
      23,690 men and 23,425 women (90%) attended. Smoking habits and previous
      cardiovascular disease were recorded; total cholesterol, high-density lipoprotein
      cholesterol (HDL cholesterol), triglycerides and blood pressure were measured.
      During subsequent follow-up (mean 6.8 years) 422 men and 54 women died from
      coronary heart disease, 514 and 114 from all cardiovascular diseases and 983 and
      404 from all causes, men and women respectively. For men, mortality decreased
      with increasing HDL cholesterol, to a minimum of around 1.5 mmol.l-1 (58 mg.dl
      1), whereafter mortality increased. This applies to coronary, cardiovascular and
      all causes of death, as well as to men with and without a history of disease. The
      association between mortality and HDL cholesterol in healthy men disappeared when
      total cholesterol was below 6.5 mmol.l-1 (251 mg.dl-1). The inverse association
      between mortality and HDL cholesterol in women was somewhat stronger than in men,
      both for coronary and cardiovascular diseases. The relative risks of coronary
      death, associated with an increase in HDL cholesterol of 0.5 mmol.l-1 (19 mg.dl
      1), from the Cox proportional hazards regression, with other major cardiovascular
      risk factors as covariates, were 0.8 (95% confidence interval: 0.6, 1.0) and 0.8
      (0.7, 1.0) for men with and without history of disease, respectively.
      Corresponding figures for women were 0.5 (0.3, 0.9) and 0.7 (0.4, 1.3).

PMID- 1396825
TI  - A possible mechanism for pacemaker-induced T-wave changes.
AB  - The genesis and the significance of pacemaker-induced T-wave changes remain
      unclear. Changes in body surface potential mapping (BSM) were observed and
      compared with resting thallium-201 myocardial scintigraphy (T1-SC) findings
      before, during and after ventricular pacing (VP) in 10 patients with various
      bradyarrhythmias. All studies were performed with the patients taking no
      medication. In all patients, isoarea QRST maps showed a characteristic abnormal
      dipolar pattern with positive values distributed over the upper chest and
      negative values over the lower chest during VP at a physiological rate for 14
      days or more. These abnormalities were preserved almost completely after pacing
      was terminated; and coincided with deep T-wave inversions in leads II, III, aVF
      and V4-6. In three patients, BSM performed before VP showed normal QRST isoarea
      maps with positive values distributed over the left lower chest. All patients in
      whom resting T1-SC was performed during chronic VP showed transient perfusion
      defects in the posteroinferior (seven cases) or inferolateral (one case) left
      ventricular wall. In three patients, T1-SC was performed before VP and showed a
      normal distribution. Both the pacing-induced perfusion defects and the T-wave
      abnormalities remained unchanged 2 h after ceasing VP, were attenuated 7 days
      later and disappeared within a month. These findings suggest that chronic
      ventricular pacing may produce myocardial ischaemia, and that it persists for a
      certain period after the cessation of pacing, resulting in post-pacing T-wave
      inversion.

PMID- 1396826
TI  - Efficacy of beta-blocking agents in reducing the number of shocks in patients
      implanted with first-generation automatic defibrillators.
AB  - The efficacy of beta-blockers was tested in 11 patients who avoided sudden death
      as a result of ventricular tachycardia or fibrillation due to coronary artery
      disease or non-ischaemic underlying heart disease, after implantation of an
      automatic defibrillator. Ten patients initially tolerated acebutolol despite
      prior class III or IV heart failure in six cases; nadolol replaced acebutolol in
      nine cases for long-term therapy. In these 10 patients, periods of treatment with
      and without beta-blocking agent were available, making possible a crossover
      comparison, during a follow-up lasting 31.6 +/- 17.8 months. One hundred and ten
      shocks were delivered: 14 were considered as probably inappropriate and ruled
      out, leaving the remaining 96 shocks to be analysed. The monthly rate of shocks
      was lower during beta-blocking treatment: 0.12 +/- 0.24 vs. 1.09 +/- 1.41 (P =
      0.03). While taking beta-blockers, only four patients received shocks, compared
      to 10 (i.e. all cases) not administered beta-blockers (P less than 0.01). Despite
      the technical limitations of the study, since only a few spontaneous shocks could
      be documented on ECG recordings, the efficacy of beta-blockers in preventing
      occurrence of severe ventricular tachyarrhythmias seems likely, and deserves
      further investigations using new implanted devices with improved memory
      functions.

PMID- 1396827
TI  - Prognosis of ventricular fibrillation in hospital.
AB  - In a retrospective study of 520 patients with in-hospital ventricular
      fibrillation 421 (81%) had acute myocardial infarction (MI), 66 (13%) had
      ischaemic heart disease (IHD) without MI, 33 (6%) had no signs of IHD. The in
      hospital mortality of these three groups was 51%, 52%, and 27%, respectively (P =
      0.01). Logistic regression analysis demonstrated that heart failure and
      cardiogenic shock were significant risk factors for in-hospital death among
      patients with IHD. Among discharged patients 1 and 5 years survival was 78% and
      51% for patients with MI, 63% and 25% for patients with IHD, 67% and 54% for
      patients without IHD. A proportional hazard model demonstrated old age, heart
      failure and cardiogenic shock as risk factors for long-term prognosis, while MI
      was associated with a reduced relative risk ratio = 0.58 of long-term mortality
      among patients with IHD. In conclusion, patients with known IHD suffering in
      hospital VF without AMI have a very poor short- and long-term prognosis. These
      patients need extensive cardiac examination.

PMID- 1396828
TI  - Improvement in the efficacy of exercise first-pass radionuclide angiocardiography
      in detecting coronary artery disease and the effect of patient age.
AB  - The most widely used criterion of normality during exercise radionuclide
      angiocardiography (a five EF units increase in left ventricular ejection fraction
      from rest to exercise) has been established in young, healthy volunteers
      resulting in a relatively low specificity when applied to older, less fit
      patients or in women. In a group of 57 patients ranging in age from 22 to 79
      years with a low likelihood of coronary artery disease, the age of the patient
      was the only independent variable predicting left ventricular ejection fraction
      change during exercise. The efficacy of a new age-based criterion for the
      diagnosis of coronary artery disease was then evaluated in 115 patients with
      chest pain undergoing both exercise first-pass radionuclide angiocardiography and
      coronary arteriography. Compared to the classic five EF unit criterion, the age
      based criterion had a higher specificity (73.2% vs 34.1% P less than 0.001)
      without significant loss in sensitivity (85.1% vs 92.6%; P = NS).

PMID- 1396830
TI  - Initial experience with a multiplane transoesophageal echo-transducer: assessment
      of diagnostic potential.
AB  - BACKGROUND: the prototype of a transoesophageal echocardiographic transducer with
      a rotatable cross-sectional scanning plane underwent initial evaluation. METHODS:
      the 5 MHz, phased array, 64 element transducer is incorporated into a 16 by 11 by
      40 mm echoscope tip. The instrument also has pulsed wave and colour flow Doppler
      capabilities. Exterior controls allow continuous mechanical rotation of the
      scanning plane from 0 degree, corresponding to the conventional transverse plane,
      through 180 degrees, thereby encompassing all possible planes. RESULTS: 103
      patients underwent examination without complications; two additional patients
      were excluded because of difficulty in swallowing the probe. Advantages include
      precise alignment of aortic valve long- and short-axis views, long-axis views of
      the ascending aorta (mean visualized length: 6 cm), and full scanning of the
      entire circumference of the mitral valve and the left ventricle. Separation of
      paravalvular and transvalvular leakage in prosthetic valves is distinctly
      improved. CONCLUSION: multiplanar transoesophageal imaging is feasible and
      increases the diagnostic yield, especially in mitral and aortic pathology and in
      the assessment of left ventricular wall motion. Three-dimensional reconstruction
      is an attractive potential application.

PMID- 1396829
TI  - Comparison of three methods of glomerular filtration rate measurement with and
      without captopril pretreatment in groups of patients with left ventricular
      dysfunction.
AB  - Methods of glomerular filtration rate measurement by 51Cr EDTA elimination,
      inulin clearance and creatinine clearance were compared with and without
      captopril pretreatment in 10 chronic heart failure patients and in 20 patients
      after transmural myocardial infarction. Strong intermethod correlations were
      found in chronic heart failure patients (EDTA: inulin r = 0.87; EDTA: creatinine
      r = 0.84; inulin: creatinine r = 0.9; all P less than 0.00001). Despite this,
      substantial absolute differences were observed in results obtained by different
      techniques. In particular, creatinine clearance significantly overestimated both
      51Cr EDTA (18.0 +/- 18.4 ml.min-1, mean difference +/- SD, P less than 0.001) and
      inulin clearance (26.8 +/- 17.0 ml.min-1, P less than 0.001). The slight
      reduction in 51Cr EDTA elimination on captopril versus placebo (-8.3 +/- 9.2
      ml.min-1, P less than 0.05) was related to a similar treatment difference in
      inulin clearance (r = 0.67, p = 0.03), but changes observed by either method were
      unrelated to captopril-induced changes in creatinine clearance. Thus, creatinine
      clearance is an unsatisfactory means of assessing the effect of angiotensin
      converting enzyme inhibition on glomerular filtration rate in chronic heart
      failure. In the post-myocardial infarction group, correlations between methods
      were poorer (EDTA: inulin r = 0.79; EDTA: creatinine r = 0.76; inulin: creatinine
      r = 0.67). In this group no significant effect of captopril on glomerular
      filtration rate was detected by any technique. As compared to the chronic heart
      failure patients, the weaker relationship between techniques post-myocardial
      infarction may be related to interference by thrombolytic or aspirin treatment.

PMID- 1396831
TI  - Compensatory regional contraction following coronary artery occlusion depends on
      subendocardial hyperaemia and hyperkinesis.
AB  - The effects of circumflex coronary artery occlusion on regional myocardial
      performance and blood flow in the left ventricular anterior wall was studied,
      using 16 thoracotomized pentobarbital-anaesthetized cats. Two pairs of ultrasonic
      crystals were placed in the midwall; one segment (longitudinal) parallel to the
      subendocardial fibres, the other (circumferential) being aligned to the fibres of
      the outer half-layer. A shunt line from the right subclavian artery to the main
      left coronary artery was unrestricted in eight cats (Group A) and clamped in
      another eight cats (Group B) until coronary perfusion pressure was clearly
      reduced with only a minor reduction in shunt flow, but without changes in global
      cardiac function. After circumflex coronary occlusion hyperkinesis was most
      pronounced in segments parallel to subendocardial fibres (longitudinal), also
      validated as a marked leftward shift in the end-systolic pressure-length relation
      of these segments. Such a shift may indicate decreased regional afterloading
      along the cardiac major axis. Hyperkinesis of longitudinal segments was
      attenuated in Group B where a fixed shunt stenosis hampered subendocardial and
      mid-myocardial hyperaemia. The lesser hyperkinesis of Group B was associated with
      decreased left ventricular systolic pressure and cardiac output. Thus, impaired
      compensatory contraction outside an acute ischaemic region was produced by a
      significant coronary stenosis which precluded the subendocardial hyperaemia and
      hyperkinesis of that region.

PMID- 1396832
TI  - Muscle energy metabolism in severe chronic congestive heart failure--effect of
      treatment with enalapril.
AB  - By using biopsies, skeletal muscle metabolism was investigated in 22 patients
      with severe chronic heart failure. All the patients were in New York Heart
      Association functional class IV and constituted a subgroup of the previously
      published CONSENSUS trial. After this initial investigation of muscle metabolism
      in patients with chronic heart failure, the influence of the angiotensin
      converting enzyme inhibitor, enalapril, on skeletal muscle metabolism was studied
      by randomizing the patients in a double-blind manner to receive either placebo (n
      = 11) or enalapril (n = 11) in addition to conventional treatment. At the time of
      inclusion, the muscle content of energy-rich compounds, i.e. glycogen and the
      high energy phosphates, adenosine triphosphate (ATP) and phosphocreatine, was
      reduced as compared with healthy subjects and muscle lactate content tended to be
      higher than normal. Following study treatment, no significant changes occurred,
      neither within nor between the two subgroups. Thus, patients with severe chronic
      congestive heart failure display metabolic derangement in muscle, which, in this
      study, was not corrected by treatment with enalapril.

PMID- 1396833
TI  - Rate of fibrinogen breakdown related to coronary patency and bleeding
      complications in patients with thrombolysis in acute myocardial infarction-
      results from the PRIMI trial.
AB  - Four hundred and one patients with acute myocardial infarction of less than 4 h
      duration were randomized to receive intravenous thrombolytic treatment with
      either 80 mg of full length unglycosylated single-chain-urokinase plasminogen
      activator (INN saruplase) or 1.5 million IU of streptokinase delivered over a 60
      min period. Angiographic patency rates were higher at 60 min in saruplase treated
      patients (71.8% vs 48%; P less than 0.001), but did not differ significantly at
      90 min (71.2% vs 63.9%; P = 0.15). Fibrinogen levels dropped markedly in both
      groups, the decrease being delayed and less pronounced with saruplase. Total
      fibrin and fibrinogen degradation products and D-dimer values rose earlier and to
      higher peak values in streptokinase treated patients. In both groups marked
      plasminogen and alpha 2-antiplasmin consumption was observed. Lower fibrinogen
      levels, and in particular the faster rate of fibrinogen breakdown, were
      associated with higher patency rates at 90 min (P less than 0.05). Patients with
      bleeding complications had lower 'lowest points' and a more rapid decrease in
      fibrinogen (P less than 0.05). These findings were not related to the drug used.
      Increased heparin levels at 6 to 12 h were correlated to bleeding complications
      in streptokinase treated patients. It is concluded that the rate of fibrinogen
      breakdown during and following thrombolytic treatment for acute myocardial
      infarction is related to early vessel patency and bleeding complications.

PMID- 1396834
TI  - Relationship among neuropeptide Y, catecholamines and haemodynamics in congestive
      heart failure.
AB  - The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was
      assessed both at baseline and during inotropic intervention in patients with
      congestive heart failure. Eighteen patients with idiopathic dilated
      cardiomyopathy (left ventricular ejection fraction (LVEF) = 26 +/- 10%) underwent
      both right and left catheterization. Haemodynamic parameters were recorded at
      baseline and during dobutamine infusion. To measure norepinephrine (NE),
      epinephrine (E) (nmol.l-1: radioenzymatic assay) and NPY (pmol.l-1:
      immunoradiometric assay) plasma concentrations, blood samples were drawn from the
      femoral artery and from the coronary sinus, both at baseline and during
      dobutamine infusion. At baseline, NPY concentration were 2.15 +/- 0.97 pmol.l-1
      in the femoral artery and 1.97 +/- 0.63 pmol.l-1 in the coronary sinus.
      Peripheral concentrations of NPY were, however, no different from those of
      patients without congestive heart failure: 2.4 +/- 2.7 pmol.l-1. Peripheral NE
      concentration was correlated to haemodynamic parameters: LVEF (r = -0.65; P less
      than 0.01), cardiac index (r = -0.54; P less than 0.05), LV end-diastolic
      pressure (r = +0.59; P less than 0.05), while peripheral NPY and E concentrations
      were not. Dobutamine improved haemodynamics, since cardiac index increased by 30%
      and LV end-diastolic pressure decreased by 40% (P less than 0.01). Peripheral NE
      concentration decreased from 6.48 +/- 4.5 to 4.82 +/- 2.69 nmol.l-1 (P less than
      0.05) but there was no change in E (0.99 +/- 0.61 vs 1.04 +/- 0.74 nmol.l-1) or
      NPY concentrations (2.41 +/- 0.99 pmol.l-1). In the coronary sinus, neither NE
      nor NPY concentrations changed during dobutamine infusion.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1396835
TI  - The heart in Duchenne muscular dystrophy: a non-invasive longitudinal study.
AB  - Sixteen boys with Duchenne muscular dystrophy (DMD) underwent serial
      investigations of echocardiographic left ventricular dimensions, systolic time
      intervals (STI), ECG and vectorcardiography (VCG). Spirometry with measurement of
      vital capacity and forced expiratory volume was also performed, as well as tests
      of muscle function. ECG was abnormal with high right precordial R-amplitudes even
      in the youngest patients. In contrast, VCG QRS area progressively diminished with
      age. STI and echocardiographic contractility indices decreased with increasing
      age. There was no clinically useful relationship between the various non-invasive
      variables on the one hand and results from skeletal muscle tests or lung function
      tests on the other, or between the different cardiac investigation methods. It is
      concluded that several non-invasive tests are needed during follow-up studies of
      Duchenne patients to evaluate the effects of treatment or assess prognosis.

PMID- 1396836
TI  - Comparison of diastolic blood pressure changes with dobutamine and exercise test.
AB  - A total of 80 patients (44 with stable angina and 36 during coronary angioplasty
      follow-up) underwent both exercise and dobutamine stress testing within one week.
      Dobutamine was infused in doses of 5 micrograms.kg-1.min-1, up to 70 every 5 min
      with blood pressure and electrocardiographic control. Treadmill exercise testing
      was performed with a maximal, symptom-limited Bruce protocol. Both systolic blood
      pressure and heart rate increased significantly with dobutamine and exercise, but
      the increase was higher with exercise (P = 0.00001). Mean blood pressure
      increased only with exercise, while diastolic blood pressure increased with
      exercise and decreased with dobutamine (P = 0.00001). A test was positive when
      either typical angina or an ST segment shift greater than or equal to 1 mm 80 ms
      after the J point was present. There were 28 positive tests with exercise and 38
      with dobutamine, 22 of them coinciding. In 36 patients both tests were negative.
      The concordance between both tests was 73%. When each test was related to
      coronary angiography, dobutamine showed greater sensitivity and efficacy than
      exercise. CONCLUSIONS: a dobutamine stress test induces a positive response in
      more patients than does an exercise stress test, although the increase in
      systolic blood pressure and heart rate is greater with exercise. The decrease in
      diastolic blood pressure with dobutamine probably plays a role in the positive
      response.

PMID- 1396837
TI  - A multicentre, randomized trial on the benefit/risk profile of amiodarone,
      flecainide and propafenone in patients with cardiac disease and complex
      ventricular arrhythmias. Antiarrhythmic Drug Evaluation Group (A.D.E.G.).
AB  - The long-term benefit/risk profiles of amiodarone, flecainide and propafenone
      were compared in 141 patients with complex ventricular arrhythmias and cardiac
      disease, in a trial designed to mimic the clinical decision-making process. The
      patients were randomized to various sequences of the three drugs, at two dose
      levels and followed for 2 years. Drug or doses were changed to deal with
      insufficient reduction of arrhythmias at 24 h ECG or severe adverse drug reaction
      (ADR). At 2 years 18 patients had died (9/18 suddenly), 19 had withdrawn because
      of major clinical events or severe ADR, 13 had dropped out, seven had been non
      responders throughout the entire sequence of drugs, whereas eight were non
      responders only at the last visit. Thus, 76 patients (54%) were responders after
      2 years. Of these, 57 were responders for 2 years with the first drug. Median
      exposure time to amiodarone, 518 days.patient-1, was higher than for flecainide
      and propafenone, 218 and 178, respectively, indicating better overall response to
      amiodarone (P less than 0.01). A total of 50 ADRs led to drug withdrawal, with
      cardiovascular ADR being less frequent (P less than 0.03) for amiodarone (2/11)
      than for flecainide (13/16) and propafenone (16/23). In conclusion, with
      sequences of amiodarone, flecainide and propafenone, an overall response rate of
      79% could be obtained in the short-term (7-28 days) and 54% at 2 years.
      Amiodarone has a more favourable therapeutic profile than flecainide and
      propafenone in these patients, having less tendency to worsen heart failure.

PMID- 1396838
TI  - Efficacy and safety of anticoagulant therapy started pre-operatively in
      preventing coronary vein graft occlusion.
AB  - Oral anticoagulant therapy with warfarin commenced pre-operatively (n = 102) to
      prevent coronary artery vein graft occlusions was compared in terms of efficacy
      and safety with dipyridamole and aspirin (n = 130) in a randomized consecutive
      series of patients. Anticoagulant therapy was started at least 2 weeks before
      coronary artery bypass surgery (CABG) and antiplatelet therapy was started at
      least 3 days before CABG with dipyridamole followed by a combination of 250 mg
      aspirin once a day via a nasogastric tube 6 h after CABG. Overall, vein graft
      patency at 3 months after surgery did not differ significantly between the
      anticoagulant group (203/275, 74%) and dipyridamole-aspirin group (238/311, 77%),
      but the occlusion rate for grafts with endarterectomy was higher in the
      anticoagulant (46%) than in the dipyridamole and aspirin group (16%), (P less
      than 0.05). The rate of peri-operative complications including deaths, re
      operation and myocardial infarction was higher in the anticoagulant than
      antiplatelet group (26.5% vs 13.8%, P less than 0.05). The occurrence of
      postoperative bleeding complications did not differ significantly between the
      groups. Thus, oral anticoagulant therapy commenced pre-operatively has no
      advantages over conventional antiplatelet therapy in patients who undergo CABG.
      Neither antithrombotic regimens proved to be satisfactory for preventing acute
      bypass vein graft occlusions in this patient population with advanced coronary
      artery disease.

PMID- 1396839
TI  - A comparison of the day-long antianginal effectiveness of nitroglycerin patches
      with that of three-times-daily isosorbide dinitrate: a double-blind study using
      dose titration.
AB  - Eight men with stable angina, a positive treadmill test, and demonstrated
      responsiveness to chronic oral isosorbide dinitrate (ISDN) were studied after
      they had been taking effective doses of ISDN t.i.d. for at least 2 weeks.
      Exercise tests were performed every 1-2 h until 19.00 hours over one day after
      the 08.00 hours application of nitroglycerin patches in a previously titrated
      dose; on another day after the administration of ISDN capsules q5h; and on a
      third day after placebo patches and capsules. The mean necessary effective patch
      dose was 125 cm2 (60-220 cm2). The mean exercise duration to angina rose from 271
      to 480 s 1 h after nitroglycerin patches (P less than 0.001). Nitroglycerin
      patches were superior to the placebo throughout the day, but in a declining
      degree--by 94 s at 19.00 hours (P less than 0.05). ISDN q5h provided peaks of
      increased walking time to angina 1 h after each dose, but after 3 h exercise time
      was down to placebo levels. Furthermore, the peaks were of diminishing amplitude:
      200 s at 09.00 hours, 150 s at 14.00 hours, but only 70 s at 19.00 hours. Thus,
      neither nitrate regimen provided continuous near-peak benefit throughout the 11 h
      period, although nitroglycerin patches had a significantly greater (P less than
      0.05) overall effect during the day.

PMID- 1396840
TI  - Effect of fentanyl on cardiac automaticity and conduction: direct or mediated
      action?
AB  - The effects of fentanyl at a dose of 100 micrograms.kg-1 on cardiac automaticity,
      refractoriness and conduction have been studied in a model of heterotopic heart
      transplantation which combines a denervated heart (donor) and a non-denervated
      heart (recipient) in each of 20 dogs employed. Once the surgical procedure had
      been completed, cycle length, sinoatrial conduction time, antegrade and
      retrograde A-V node block points, cycle length at which 1:1 conduction ceases to
      exist and the antegrade effective refractory period of the A-V node and
      ventricles were measured. These parameters were determined in hearts both in the
      basal situation and 10 min after fentanyl injection. In the recipient organs,
      fentanyl produced statistically significant prolongation of cycle length,
      sinoatrial conduction time, antegrade block point and antegrade effective
      refractory periods of the A-V node and ventricles, with respect to the basal
      situation (P less than 0.01 for all these parameters); in 20% of cases, a
      complete A-V block was produced. In the donor hearts (denervated), prolongations
      of cycle length (P less than 0.01) and the antegrade block point (P less than
      0.05), as compared with the basal situation, were recorded, but no other
      modifications were detected. To test whether these effects were due to the action
      of fentanyl, 10 animals were subsequently injected with naloxone, an agent which
      reverted the reported changes, although in the recipient organs, there persisted
      a slight prolongation of the cycle length with respect to basal measurements (P
      less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396841
TI  - A closed-chest myocardial occlusion-reperfusion model in the pig: techniques,
      morbidity and mortality.
AB  - Extensive preparative surgery and lengthy experimentation may lead to high rate
      of complications and mortality in myocardial ischaemia studies. These problems
      are particularly common when pigs are used as the subject as they are prone to
      develop lethal ventricular arrhythmias. Here, a closed-chest model is presented,
      in which the trauma of major preparative surgery is avoided. One-hundred and
      twelve pentobarbital-anaesthetized, mechanically ventilated pigs were used.
      Coronary occlusion was produced by injection of a 2 mm diameter ball via a
      modified coronary angiography catheter. Reperfusion was induced by retraction of
      the ball via a thin filament attached to the ball. The amount of the myocardium
      at risk (MAR) was 8.23 +/- 2.41% (mean +/- SD) of the left plus right ventricular
      weight. It was possible to carry out scheduled 24 h experiments in 87 out of 93
      animals (93.5%). Preparative mortality was 1.8% and 24 h mortality 6.5%.
      Ventricular fibrillation (VF) occurred during preparation in 3.6%, during
      coronary occlusion in 7.3% and during reperfusion in 5.0% of the animals. VF was
      significantly related to a large zone of MAR and insufficient premedication.
      Catheter- or ball-induced complications were found in 10.7%. Mortality and
      incidence of VF are considerably lower in this closed-chest model than in a
      previously reported open-chest pig preparation.

PMID- 1396842
TI  - Increase in radionuclide left ventricular ejection fraction after cardioversion
      of chronic atrial fibrillation in idiopathic dilated cardiomyopathy.
AB  - To assess the potential improvement in left ventricular ejection fraction after
      cardioversion of chronic atrial fibrillation to sinus rhythm in idiopathic
      dilated cardiomyopathy, we studied prospectively 17 patients, aged 58 +/- 6
      years, by radionuclide angiocardiography at rest. Left ventricular ejection
      fraction was determined before treatment and at a mean delay of 4.7 months after
      cardioversion. Return to sinus rhythm was obtained in 12 patients,
      pharmacologically or by electrical cardioversion. Five patients remained in
      atrial fibrillation. No clinical, echocardiographic or haemodynamic finding could
      predict the success of cardioversion. In chronic atrial fibrillation, the
      ejection fraction did not change significantly: 30.0 +/- 9.1% (19 to 44%) at the
      first evaluation and 29.5 +/- 8.3% (22 to 41%) after 4.7 months. After successful
      cardioversion, left ventricular ejection fraction improved from 32.1 +/- 5.3% (24
      to 41%) to 52.9 +/- 9.7% (37 to 71%) (P less than 0.001). The difference was 20.8
      +/- 11.3% and left ventricular ejection fraction was normalized in 50% (6/12) of
      the patients. There was a significant reduction in the cardiothoracic ratio on
      chest X-rays and of the left ventricular end-diastolic diameter on
      echocardiography; fractional shortening increased (27.7 +/- 4.3% vs 20.3 +/-
      2.7%, P less than 0.01). A third evaluation was realized after a mean delay of
      11.7 months in the patients with successful cardioversion. Sinus rhythm was
      present in 83% (10/12) of the patients: seven patients were reevaluated by
      radionuclide angiography. The improvement in left ventricular function observed
      at the 4.7 months evaluation was still present. In two patients with recurrence
      of atrial fibrillation, there was a severe deterioration of left ventricular
      systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396843
TI  - Laser-assisted tricuspid valve balloon dilation for acquired tricuspid valve
      atresia.
AB  - Acquired pulmonary valve atresia is a well-recognized but uncommon complication
      of surgical systemic-to-pulmonary artery shunts in patients with tetralogy of
      Fallot. Acquired atresia of the tricuspid valve, however, has not been reported
      previously. This complication developed in a 3-year-old girl, with pulmonary
      atresia and an intact ventricular septum, after a Blalock-Taussig shunt and right
      ventricular outflow tract reconstruction. Percutaneous transcatheter laser
      assisted balloon dilation re-established antegrade flow across the tricuspid
      valve.

PMID- 1396844
TI  - Cardiac failure secondary to hypocalcaemia of nutritional osteomalacia.

PMID- 1396845
TI  - Screening results used to assess the prevalence of haemochromatosis in a Swedish
      male pacemaker-treated population.

PMID- 1396846
TI  - Central control of blood pressure.

PMID- 1396847
TI  - Monitoring of sympathetic activity in man: physiology and pharmacology.

PMID- 1396848
TI  - Haemodynamic effects of a new multifactorial antihypertensive drug.

PMID- 1396849
TI  - Higher left ventricle mass in normotensives with exaggerated blood pressure
      responses to exercise associated with higher ambulatory blood pressure load and
      sympathetic activity.

PMID- 1396850
TI  - Cardiovascular risk factors and antihypertensive treatment.

PMID- 1396851
TI  - Influence of urapidil and other antihypertensive agents on lipids and glucose
      metabolism in hypertensive patients.

PMID- 1396852
TI  - Pharmacotherapeutic effects of antihypertensive agents on myocardium and coronary
      arteries in hypertension.
AB  - Hypertensive left ventricular hypertrophy comprises myocyte hypertrophy,
      interstitial fibrosis and structural alterations in the coronary
      microcirculation. This leads to impairment of diastolic function in the left
      ventricle and coronary flow reserve despite normal epicardial arteries.
      Consequently, antihypertensive treatment should aim at (1) reversing myocyte
      hypertrophy, (2) restoring myocardial structure and (3) improving coronary flow
      reserve without lowering blood pressure. In recent years many clinical studies
      have shown that regression of hypertensive hypertrophy can be induced by long
      term treatment with ACE inhibitors, calcium-channel blockers, beta-receptor
      blockers and antisympathonic drugs. However, vasodilators and diuretics, which
      stimulate adrenoceptor activity and increase angiotensin II levels, were found to
      be less effective in reversing left ventricular hypertrophy. The trophic
      influence of catecholamines and angiotensin II on the myocardium counteracts the
      effect of systolic wall stress reduction due to blood pressure lowering. As
      regards reversal of interstitial fibrosis, ACE inhibitors seem to be effective,
      because fibroblast growth was found to be stimulated by angiotensin II. Recently,
      clinical studies have confirmed previous experimental data that improvement in
      impaired coronary vasodilator reserve can be realized by long-term
      antihypertensive therapy. In adopting an antihypertensive treatment strategy
      prime consideration should be given to reversal of cardiac remodelling through
      restoration of myocardial structure and repair of the coronary microcirculation.

PMID- 1396853
TI  - Impact of regression of left ventricular hypertrophy on cardiac function in
      hypertension.
AB  - It is now established that regression of left ventricular hypertrophy (LVH)
      occurs following reduction of arterial pressure in patients with hypertension. A
      number of factors contribute towards this regression, including the fall in blood
      pressure itself, the drug therapy given, and the pre-existing degree of
      hypertrophy. LVH is in some senses a beneficial adaptive response in terms of
      systolic function, and therefore it is important to clarify whether or not
      regression of hypertrophy is damaging to cardiac function. Overall assessment of
      these effects has been more difficult because the antihypertensive drug therapy
      and the changes in blood pressure also contribute to left ventricular function.
      Current data indicate that systolic function is maintained both at rest and
      following exercise but not necessarily improved. In contrast, diastolic function
      in some but not all studies, has been shown to have been improved. Recent
      information has allayed fears that regression of LVH may cause a deterioration in
      function if blood pressure is allowed to return to its pretreatment levels. It
      would appear that in this situation function is maintained both at rest and
      during exercise. Finally, the assessment of cardiac function following regression
      of hypertrophy remains a surrogate end-point. The key information required
      remains the influence of regression of hypertrophy and its alteration in function
      on morbidity and mortality in patients with hypertension.

PMID- 1396854
TI  - Morphometric investigation of human myocardium in arterial hypertension and
      valvular aortic stenosis.
AB  - Both arterial hypertension and aortic stenosis lead to pressure overload of the
      left ventricle. As intramyocardial vasculature is confronted with pressure
      overload in hypertension but not in aortic stenosis, structural differences are
      to be expected in both forms of left ventricular hypertrophy. With the aid of
      morphometry, we investigated human myocardium from autopsied hearts from six
      patients with arterial hypertension and 10 controls, as well as myectomy
      specimens from cardiac surgery from 14 patients with aortic stenosis. Mean left
      ventricular myocytic diameter was significantly (P less than 0.05) increased
      compared with controls (12.4 +/- 1.5 microns) during hypertension (+27%) as well
      as aortic stenosis (+65%) (P less than 0.05). This was combined with a greater
      volume density of perimyocytic fibrosis (controls = 0.8 +/- 0.4 V upsilon %)
      during hypertension (+250%) and aortic stenosis (+587%) (P less than 0.05). Walls
      of intramyocardial arterioles (external diameter 20-40 and 40-80 microns) were
      thickened to 32% and 44% (P less than 0.05) during hypertension, but not during
      aortic stenosis. Compared with controls, perivascular fibrosis of these
      arterioles was increased by +215% and 61% (P less than 0.05), respectively,
      during hypertension, but not during aortic stenosis. CONCLUSIONS: Myocytic
      hypertrophy and increased perimyocytic fibrosis accompany intraventricular
      pressure overload (hypertension and aortic stenosis) in human hearts. Myocardial
      structure as a result of arterial hypertension, but not aortic stenosis, is also
      characterized by intramyocardial arteriole wall-thickening and increased
      perivascular fibrosis. Thus, distinct structural reaction patterns are noted in
      the cardiac hypertrophy associated with hypertension and aortic stenosis.

PMID- 1396855
TI  - Biological basis of diastolic dysfunction of the hypertensive heart.
AB  - To study the diastolic properties of the heart includes examining active
      relaxation, passive ventricular stiffness and atrial contraction. (i) The main
      determinant of active relaxation is the adenosine triphosphate (ATP)
      concentration. Relaxation needs to occur so that the ATP content of the cell can
      be decreased by activation of the myosin ATPase, which in turn depends upon an
      intracellular messenger, elevation of the calcium transient. In a model of
      cardiac hypertrophy active relaxation is always slower. This slowing accompanies
      a slowing of the calcium transient, a diminution in the activity of the Na+/Ca2+
      exchanger, a change in the properties of Na+, K+ ATPase and a decreased
      concentration of Ca2+ ATPase in the sarcoplasmic reticulum. (ii) Chamber
      stiffness is likely to be increased only in relation to the degree of ventricular
      hypertrophy. The main, if not unique, determinant of ventricular diastolic tissue
      stiffness is the structure and concentration of the collagen. Consequently tissue
      stiffness is augmented in cardiac hypertrophy in which the ventricular collagen
      concentration is elevated. It is important that both clinically and
      experimentally cases of cardiac hypertrophy, even those resulting from pressure
      overload in which myocardial stiffness and cardiac collagen concentration remain
      unchanged, have been documented. A good example of this is the DOCA-salt model of
      arterial hypertension. (iii) Atrial contraction is normally more rapid than
      ventricular contraction, the biological basis for which is the difference in
      isomyosin content.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396856
TI  - Myocardial collagen matrix remodelling in arterial hypertension.
AB  - The cardiac interstitium is composed of non-myocyte cells and a structural
      fibrillar protein network which plays a dominant role in governing the structure,
      architecture, and mechanical behaviour of the myocardium. Herein we review the
      fibrillar collagen network, its various components, and the functions they serve
      in the normal and structurally remodelled myocardium in arterial hypertension.
      The heterogeneity in myocardial structure, created by the altered behaviour of
      non-myocyte cells, particularly cardiac fibroblasts, which are responsible for
      collagen synthesis or degradation and thereby fibrous tissue accumulation, is a
      major determinant for the appearance of diastolic dysfunction and ultimately
      systolic myocardial failure. Regulatory mechanisms related to this fibrous tissue
      response are reviewed to draw attention to the hitherto neglected role of cardiac
      fibroblasts in mediating adverse structural remodelling of the myocardium and
      showing how this can be prevented through the use of pharmacological agents that
      interfere with the regulation of the myocardial collagen matrix. Several lines of
      evidence suggest that circulating and tissue renin-angiotensin-aldosterone
      systems (RAAS) are involved in the structural remodelling of the non-myocyte
      compartment. These include the cardioprotective effects of angiotensin converting
      enzyme (ACE) inhibition and aldosterone receptor antagonism that were found to
      prevent myocardial fibrosis in the rat with renovascular hypertension. In the rat
      with genetic hypertension, established left ventricular hypertrophy and abnormal
      myocardial diastolic stiffness due to interstitial fibrosis, RAAS inhibition
      resulted in restoration of myocardial structure and function to normal.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396857
TI  - Right ventricular performance in arterial hypertension.
AB  - To investigate right ventricular function, 24 patients with arterial hypertension
      and five normotensive controls underwent equilibrium radionuclide
      ventriculography with simultaneous right heart catheterization. In normal
      subjects, left ventricular ejection fraction was 57 +/- 2% at rest and 71 +/- 5%
      on effort, and right ventricular ejection fraction (RVEF) averaged 51 +/- 5% at
      rest and 65 +/- 2% during exercise. Pulmonary vessel resistance (PVR) was 56 +/-
      37 dyn.s.cm-5 at rest and 46 +/- 10 dyn.s.cm-5 on effort. Hypertensive patients
      were divided into three groups according to their left ventricular function:
      group 1 (n = 10) had normal left ventricular ejection fraction (LVEF) at rest and
      on effort (57 +/- 9%; 65 +/- 6%), in this group, right ventricular systolic
      reserve was reduced (RVEF 52 +/- 7% at rest, ns; RVEF 57 +/- 7% on effort, P less
      than 0.01 compared to controls). Pulmonary vessel resistance during exercise
      averaged 78 +/- 24 dyn.s.cm-5, which was significantly higher compared to
      controls (P less than 0.01). In group 2, left ventricular contractions were
      normal at rest (60 +/- 6%, ns) but deteriorated during exercise to 56 +/- 8% (P
      less than 0.001, compared to controls). These patients also showed a lack of
      right ventricular augmentation at ejection fraction (54 +/- 8% at rest, ns; 56 +/
      8% under exercise, P less than 0.05). PVR was significantly enhanced during
      exercise (88 +/- 40 dyn.s.cm-5, P less than 0.05 compared to controls).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396858
TI  - The role of coronary perfusion pressure.
AB  - Coronary flow is normally autoregulated so that within wide limits of changes in
      perfusion pressure (which approximate to diastolic BP) blood flow to the heart
      remains constant. Thus, as perfusion pressure falls, the coronary arterioles
      dilate to maintain flow; under basal conditions a five-fold increase in coronary
      flow can occur, i.e. a flow reserve of five. Coronary flow reserve is markedly
      impaired in the presence of severe coronary artery stenosis and/or LVH. In the
      presence of severe stenosis and LVH a fall in perfusion pressure (DBP), which
      would be normally well tolerated, results in a fall of coronary flow, ECG changes
      and ventricular dysfunction (fall in ejection fraction instead of the usual
      increase). The above mechanisms underlie the J-curve relationship between DBP and
      myocardial infarction (MI) in high risk hypertensives. In the absence of overt
      coronary artery disease (CAD) and LVH, the lower the DBP the better. However in
      the presence of CAD and LVH lowering the DBP (phase 5) to below the low-mid 80s
      results in an increased frequency of MI.

PMID- 1396859
TI  - Coronary haemodynamics in hypertensive heart disease.
AB  - Cardiac constituents affected in arterial hypertension comprise the myocardium,
      interstitium and coronary circulation. With regard to coronary circulation,
      arterial hypertension is an important risk factor in coronary artery disease, but
      even in the absence of coronary artery disease, hypertensive patients frequently
      have angina pectoris or reveal electrocardiographic abnormalities suggestive of
      myocardial ischaemia due to coronary insufficiency. Under clinical conditions,
      determination of coronary flow reserve (dipyridamole; Argon-method) allows for
      the evaluation of impairment of coronary regulatory reserve. In comparison to
      healthy normotensives, coronary haemodynamics in hypertensive patients with
      microvascular angina are characterized by a severely increased minimal coronary
      resistance and reduced maximal coronary blood flow to dipyridamole. Accordingly,
      coronary reserve is markedly reduced by about 40%, and metabolic, myocardial and
      vascular factors may be involved in this reduction. In the compensated stage of
      arterial hypertension, with concentric left ventricular hypertrophy, myocardial
      factors, such as myocyte hypertrophy, extravascular compressing forces and
      functional implications of impaired relaxation, as well as metabolic factors,
      contribute to impairment in coronary reserve to a minor extent. The reduction in
      coronary flow reserve is not proportional to the elevation in left ventricular
      muscle mass and thus the degree of left ventricular hypertrophy does not seem to
      determine the reduction in vasodilator reserve directly. Thus the reduction in
      coronary reserve seems to be primarily the consequence of an impaired
      vasodilating capacity of the coronary resistance vessels, as indicated by a
      severely increased minimum coronary resistance to dipyridamole, i.e. a severely
      reduced overall coronary conductance capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396860
TI  - Heterogeneity of endothelial dysfunction in hypertension.
AB  - The endothelium may play a role as a target and mediator of hypertension. Due to
      its anatomical position, it is very exposed to mechanical forces; as a source of
      vasoactive material it may participate in increasing peripheral vascular
      resistance and in promoting local ischaemia in the heart and brain. Morphological
      and functional changes in the endothelium occur in experimental and human
      hypertension. However, the severity of the defect and the mechanisms involved
      among vascular beds and models of hypertension are heterogeneous. Endothelium
      dependent relaxations are impaired in the aorta, carotid artery and in cerebral
      and mesenteric arterioles in hypertension. In the coronary circulation the defect
      is less pronounced. The mechanisms involve a reduced formation of nitric oxide,
      an enhanced production of prostaglandin H2 and an impaired responsiveness of
      vascular smooth muscle to nitric oxide. The role of endothelin in hypertension is
      controversial; circulating levels appear unaltered except in the presence of
      renal failure or atherosclerosis. The local vascular production of endothelin,
      however, may still be increased. The potentiating effects of threshold
      concentrations of endothelin on the vasoconstrictor response to noradrenaline are
      enhanced in hypertension. Thus, subtle and distinct endothelial function defects
      occur in hypertension, but not all vascular beds are similarly affected and
      different mechanisms contribute. Endothelial dysfunction may contribute to
      increased peripheral resistance, tissue ischaemia and cardiovascular
      complications.

PMID- 1396862
TI  - Transient myocardial ischaemia in hypertensives: missing link with left
      ventricular hypertrophy.
AB  - Hypertensive patients often complain of angina pectoris in spite of a normal
      coronary angiogram. The aim of this study was to establish whether
      electrographical signs of transient myocardial ischaemia during 24-h ST Holter
      monitoring are associated with an increased left ventricular muscle mass. Thirty
      five hypertensive patients were studied by 24-h Holter monitoring and M-mode and
      two-dimensional echocardiography. For control purposes nine normotensives were
      studied by the same protocol. Hypertensives with and without ST-segment
      depression did not differ in respect of blood pressure or left ventricular muscle
      mass (162.9 +/- 80 vs. 162.3 +/- 53 g m-2). Since both groups only showed a
      borderline left ventricular hypertrophy, the myocardial factor does not seem to
      be important for the occurrence of ST segment depression. Primary functional and
      structural alterations at the microcirculation level seem to be responsible for
      the occurrence of transient episodes of ST segment depression in the Holter
      electrocardiogram, indicating transient myocardial ischaemia.

PMID- 1396861
TI  - Metabolically-modulated growth and phenotype of the rat heart.
AB  - Heart muscle reacts to work overload and various neuroendocrine stimuli by
      inducing myocyte growth. A novel type of hypertrophy can be induced in the rat
      heart by etomoxir, which reduces fatty acid oxidation. This hypoglycaemic drug
      inhibits the mitochondrial carnitine palmitoyltransferase 1, and thus reduces the
      long-chain fatty acid uptake of mitochondria; in a compensatory manner, the
      glycolytic flux is enhanced. In rats, etomoxir induced a harmonious growth of the
      left and right ventricles of normal and pressure-overloaded hearts. To
      characterize the protein phenotype, myosin expression and sarcoplasmic reticulum
      (SR) Ca2+ pump activity were determined. In contrast to pressure-overloaded
      hearts, etomoxir increased the proportion of myosin V1, Ca(2+)-stimulated SR
      ATPase activity and the rate of SR Ca2+ uptake. Since etomoxir did not increase
      blood pressure, heart rate or circulating thyroid hormones, it appears that
      established mechanisms of other models of cardiac hypertrophy were not involved.
      The etomoxir-induced changes thus seem closely linked to the shift in energy
      metabolism.

PMID- 1396863
TI  - Hypertension, left ventricular hypertrophy, ventricular arrhythmias and sudden
      death.
AB  - LVH is a common sequela of arterial hypertension; it increases the risk of sudden
      death and other cardiovascular morbidity and mortality independent of arterial
      pressure and has been associated with ventricular arrhythmias.
      Electrophysiological studies suggest a connection between ventricular arrhythmias
      in patients with LVH and sudden death. LVH can be reduced by specific
      antihypertensive therapy, although not all drugs are equipotent in this regard. A
      reduction in LVH has been shown to diminish ventricular ectopy. Preliminary
      findings suggest that a reduction of LVH and associated arrhythmias may reduce
      its inherent cardiovascular risk.

PMID- 1396864
TI  - Electrophysiological and therapeutic implications of cardiac arrhythmias in
      hypertension.
AB  - Hypertension, especially if associated with left ventricular hypertrophy (LVH),
      is a risk factor in complex ventricular arrhythmia (VA) and sudden cardiac death
      (SCD). To determine the effectiveness of the clinical use of programmed
      ventricular stimulation (PVS) we studied 40 symptomatic hypertensive patients
      after excluding coronary heart disease (CHD), as characterized by dizziness and
      palpitation, syncope, aborted SCD and/or documented complex VA. PVS revealed a
      normal result, i.e. a maximum of six ventricular echobeats, in 70% (group A) and
      a pathological result, i.e. ventricular tachycardia (VT) or fibrillation (VF) in
      30% (group B). Both groups differed significantly with respect to LV (left
      ventricular) muscle mass: 158 +/- 45 (A) vs. 222 +/- 112 (B) g.m-2, LVEF (left
      ventricular ejection fraction): 71 +/- 17% (A) vs. 47 +/- 18% (B) and LV end
      systolic volume index: 34 +/- 25 (A) vs. 63 +/- 27 (B) ml.m-2. Coronary reserve
      was comparably reduced in both groups: 2.6 +/- 1.0 (A) vs. 2.3 +/- 0.6 (B). In
      3/8 (37%) patients with aborted SCD and VT/VF the clinical VA (2/2 VT and 1/6 VF)
      could be induced, whereas in the remaining five patients nsVT or no complex VA
      was induced. The therapeutic regimen included no drugs in 30%, beta-blockers in
      50%, serial drug testing in 12% and implantation of an automatic cardioverter
      defibrillator (AICD) in 8% of patients. Ventricular late potentials (LPs),
      detected by the signal averaging electrocardiogram, represent zones of delayed
      myocardial activation, which may become an origin of ventricular tachycardias.
      Three criteria constitute a positive LP: (1) QRS duration greater than 114 ms,
      (2) root mean square voltage of the last 40 ms less than 20 microV and (3)
      duration of low amplitude signal below 40 microV greater than 38 ms. To look for
      the prognostic value of LP in hypertension we investigated 43 hypertensive
      patients without evidence of CHD. All three criteria were positive in 4/43
      patients (9%), three of them demonstrating inducible monomorphic VT during PVS.
      17/30 patients (56%) with LVH had at least one positive criterion, whereas only
      one out of 13 patients without left ventricular hypertrophy (8%) had one positive
      criterion. Symptomatic patients presenting with syncope, aborted SCD or
      documented VT/VF differed significantly from patients without symptoms or complex
      arrhythmias in regard to all three criteria. CONCLUSION: In hypertensive heart
      disease clinical arrhythmias as well as the result of electrophysiological
      testing are closely related to left ventricular performance and
      hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1396865
TI  - Left ventricular hypertrophy as a risk factor in arterial hypertension.
AB  - Data on the evolution and prognostic implications of left ventricular hypertrophy
      (LVH) determined by ECG, chest X-ray and echocardiogram in the Framingham Study
      are reviewed. Echocardiographic examination provides the most sensitive and
      specific measure of left ventricular hypertrophy, providing a quantitative
      evaluation of the anatomical condition. Chest X-ray evaluation is also more
      sensitive than the ECG, but less specific than the echocardiogram. When ECG-LVH
      is present, X-ray and echocardiographic LVH are often found; but, when negative,
      the ECG clearly does not exclude anatomical LVH. The incidence of each variety of
      LVH increases with age, weight and blood pressure. Although it may also appear
      following coronary heart disease (CHD), valvular deformity and congenital cardiac
      defects, the former are the major determinants of LVH in the general population.
      Each contributes independently to the occurrence of LVH. LVH has emerged as a
      powerful non-invasive indicator of increased vulnerability to the occurrence of
      major cardiovascular disease outcomes in hypertension. It appears that X-ray and
      echocardiographic LVH measure anatomical hypertrophy, whereas the ECG variety is
      also indicative of ischaemic myocardial involvement when repolarization
      abnormality is present. Hypertension clearly predisposes to both anatomical and
      ECG-LVH which cannot be taken as an incidental compensatory feature since at any
      blood pressure those with ECG-LVH, X-ray or echo LVH are distinctly more prone to
      cardiovascular sequelae. ECG-LVH carries a greater risk than anatomical (X-ray)
      LVH. ECG-LVH with repolarization abnormality is more dangerous than that with
      voltage alone. The latter appears to reflect chiefly the severity and duration of
      accompanying hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396866
TI  - The role of hypertension, left ventricular hypertrophy and psychosocial risks in
      cardiovascular disease: prospective evidence from blue-collar men.
AB  - Epidemiological studies have demonstrated that, compared with the population as a
      whole, there is increased cardiovascular morbidity and mortality among lower
      socio-economic groups. To explore determinants of the increased risk within this
      group, a prospective 6.5 year investigation of a cohort of 416 middle-aged (40.8
      +/- 9.6 years) male blue-collar workers was undertaken. In addition to
      established somatic and behavioural risk factors, psychosocial influences that
      measured chronic occupational stress in terms of an imbalance between high effort
      and low reward were assessed. Multivariate logistic regression analysis shows
      that hypertension (odds ratio (o.r.) 3.85; 95% CI 1.59-9.34), left ventricular
      hypertrophy (o.r. 3.62; 95% CI 1.06-12.37), hyperlipidaemia (o.r. 2.55; 95% CI
      1.08-6.00), status inconsistency (measuring low reward at work) (o.r. 2.86; 95%
      CI 1.04-7.80) and 'immersion' (measuring high intrinsic effort at work) (o.r.
      3.57; 95% CI 1.22-10.47) independently contribute to the prediction of fatal or
      non-fatal cardiovascular events (acute myocardial infarction, stroke). Expected
      probabilities of cardiovascular events are clearly elevated if the combined
      effects of left ventricular hypertrophy and psychosocial risks are analysed. In
      conclusion, increased incidence of cardiovascular disease among lower socio
      economic groups is explained by a co-manifestation of established risk factors
      including left ventricular hypertrophy (by ECG) and psychosocial factors
      measuring chronic stress at work.

PMID- 1396867
TI  - The reorganization of the human and rabbit heart in response to haemodynamic
      overload.
AB  - A myothermal/mechanical analysis on non-failing and failing human hearts and
      normal and pressure overloaded rabbit hearts is reported. Heat production is
      partitioned into tension-dependent and tension-independent components together
      with force measurements to provide information about calcium and cross-bridge
      cycling. In the non-failing human heart the cross-bridge force-time integral is
      0.51 +/- 0.06 (ns). This value is increased to 0.97 +/- 0.09 (P less than 0.05 s)
      in failing hearts. In control as compared to pressure-overload rabbit hearts the
      cross-bridge force-time integral increases from 0.36 +/- 0.02 to 0.96 +/- 0.11 (P
      less than 0.05 s). The increase in force-time integral allows the heart muscle to
      develop force with greater economy (less high energy phosphate hydrolysis) but at
      the expense of velocity and power. The amount of calcium cycled following
      activation in non-failing human hearts is 32.2 +/- 8.17 nmoles.g-1.-beat-1. In
      the failing preparations calcium cycling is reduced to 16.7 +/- 1.72 nmoles.g-1.
      beat-1. In pressure-overloaded hypertrophied, as compared with control rabbit
      hearts, the calcium cycled per beat is reduced from 43.0 +/- 7.3 to 17.6 +/- 3.4
      nmoles.g-1. It is suggested that the alterations in cross-bridge cycling are more
      likely to be related to isoenzyme shifts in light chains or troponin T than to
      myosin isoforms. The calcium cycling changes are well correlated with changes in
      the sarcoplasmic reticular and sarcolemmal calcium transport proteins. The
      alterations in the contractile and excitation contractions coupling systems
      contribute to the functional changes observed in the failing human and pressure
      overload rabbit hearts.

PMID- 1396869
TI  - Toward a useful measure of flood-field uniformity: can the beauty in the eye of
      the beholder be quantified?

PMID- 1396868
TI  - Reduced peripheral and coronary vasomotion in systemic hypertension.
AB  - In 53 patients with a history of arterial hypertension and 16 normotensive
      control subjects, coronary blood flow reserve by means of the argon method, and
      peripheral vascular flow reserve by means of venous occlusion plethysmography,
      were studied. The coronary flow reserve, expressed as the ratio of coronary
      vascular resistance under resting conditions to the minimal coronary vascular
      resistance after the administration of dipyridamole, was 4.34 +/- 0.89 in the
      normotensive group and 2.18 +/- 0.60 in the hypertensive group. There was no
      significant difference in forearm peak flow after 3 min of arterial occlusion
      between normotensive and hypertensive patients, while the peripheral minimal
      vascular resistance was significantly higher in hypertensive patients (8.8 +/-
      3.8 mmHg x ml.min-1 x 100 ml-1 tissue) as compared to normotensive subjects (6.37
      +/- 2.37 mmHg x ml.min-1 x 100 ml-1 tissue). Parallel to the reduction in
      coronary reserve, the peripheral flow reserve, expressed as the ratio of
      peripheral resting vascular resistance to peripheral minimal vascular resistance
      after 3 min of arterial occlusion, was significantly lower (P less than 0.01) in
      hypertensive subjects (3.85 +/- 2.28) as compared to normotensive subjects (5.31
      +/- 1.72). These data suggest that in hypertensives an impaired vasodilator
      reserve of both coronary and peripheral microcirculation exists.

PMID- 1396870
TI  - In vitro and in vivo effects of diethylene triamine penta-acetic acid on the
      distribution of indium-111 monoclonal antibody metabolism.
AB  - The effects of diethylene triamine penta-acetic acid (DTPA) on indium-111
      monoclonal antibody (MoAb) metabolism were examined. Sequential analysis of 111In
      MoAb incubated in serum at 37 degrees C by high performance liquid chromatography
      (HPLC) and electrophoresis revealed that the radioactivity gradually moved from
      the MoAb to a 70-90 kDa molecular weight fraction. DTPA inhibited the
      transchelation of 111In to this fraction. It also decreased 111In uptake by
      isolated rat hepatocytes but did not remove 111In incorporated in hepatocytes.
      The daily in vivo administration of DTPA (0.5-2.0 mg/mouse daily) to athymic mice
      after 111In-MoAb injection significantly reduced the 111In uptake in the liver
      and kidney. The tumour uptake was decreased somewhat but not significantly. The
      serum radioactivity in the 70-90 kDa fraction was also decreased. Scintigraphic
      examination demonstrated a decreased liver uptake in the DTPA-treated group of
      mice. Our results show that 111In released from the DTPA-MoAb conjugate in serum
      binds to molecules of 70-90 kDa and that DTPA decreases the 111In uptake in this
      fraction, which induces a decrease of 111In accumulation in normal tissues.

PMID- 1396871
TI  - The effect of hydration on the dose to the urinary bladder wall during technetium
      99m diethylene triamine penta-acetic acid renography.
AB  - A spherical bladder dynamic model for the estimates of the radiation dose to the
      bladder walls from intravenously injected radionuclides was implemented to
      investigate in theory the effect of hydration on the reduction of the bladder
      dose in technetium-99m diethylene triamine penta-acetic acid (99mTc) DTPA
      renography. This model gives due consideration to the variation with time of the
      urine flow rate to the bladder, following a known fluid load. According to the
      model, the estimated dose depends on the renal function, the fluid load, the time
      elapsed from the fluid load to the i.v. DTPA injection, the micturition volume
      and the residual urine volume. Experimental data concerning the values of these
      parameters for normal individuals were obtained from the literature. Calculations
      cover the time period from i.v. injection up to the time of the ninth
      postinjection void. Results show that the patient's condition of hydration is
      critical for the radiation protection of the bladder. It is shown that optimum
      combinations of the values of the parameters involved in the calculations exist,
      which minimize the radiation dose. On the basis of these results, a general
      protocol is proposed, referring to the hydration conditions under which the renal
      dynamic study may be normally carried out, with a minimal absorbed dose to the
      bladder walls (less than 0.045 mGy/MBq).

PMID- 1396872
TI  - Heterogeneous myocardial distribution of iodine-123 15-(p-iodophenyl)-3-R,S
      methylpentadecanoic acid (BMIPP) in patients with hypertrophic cardiomyopathy.
AB  - IT has been proposed that iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic
      acid (123I-BMIPP) is an agent for myocardial fatty acid metabolism in animal
      models. The aim of the present study was to determine whether alterations in
      fatty acid uptake and/or utilization in patients with hypertrophic cardiomyopathy
      (HCM) could be detected by 123I-BMIPP. Myocardial imaging with 123I-BMIPP and
      thallium-201 (201Tl) was performed in 14 fasted patients. A dose of 111 MBq of
      123I-BMIPP was administered intravenously at rest, and myocardial emission
      computed tomography was obtained 20 min and 3 h after injection. The 201Tl
      imaging was also performed within 1 week after the 123I-BMIPP study. The regional
      myocardial uptake and clearance of 123I-BMIPP and 201Tl were assessed
      quantitatively. The myocardial distribution of 123I-BMIPP was more heterogeneous
      than that of 201Tl in patients with HCM. The myocardial uptake of 123I-BMIPP was
      lower in the anteroseptal region of the left ventricle than in the posterolateral
      region (74% vs. 85%, P less than 0.001). The anteroseptal wall showed a faster
      clearance of 123I-BMIPP than the posterolateral wall (33% vs. 27%, P less than
      0.01). Both a decreased uptake and rapid clearance of 123I-BMIPP were observed in
      the hypertrophied myocardium of the anteroseptal wall, where 201Tl uptake was
      normal or even increased. Myocardial segments with a markedly increased thickness
      showed a lower uptake and faster clearance of 123I-BMIPP than those with mild
      hypertrophy (uptake 73% vs. 82%, P less than 0.05; clearance 30% vs. 25%, P less
      than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1396873
TI  - The clinical impact of thallium-201 reinjection scintigraphy for detection of
      myocardial viability.
AB  - In a clinical study, the value of thallium-201 reinjection was studied in 139
      patients with suspected or known coronary artery disease who showed one or more
      persistent defects after conventional stress-redistribution imaging. Fifty-nine
      (42%) patients had sustained a Q-wave myocardial infarction. Sixty-eight (49%)
      patients showed a reversible defect in at least one myocardial segment at
      redistribution, while 71 (51%) had persistent defects only. Following reinjection
      additional segmental filling-in was seen in 95 (68%) patients, including 50 of
      the 68 (74%) patients with reversible defects and 45 of the 71 (63%) with
      persistent defects only. On the immediately post-exercise images, 458 (47%) of
      973 segments showed perfusion defects. At redistribution 105 (23%) of the 458
      defects showed filling-in, whereas of the remaining 353 persistent defects 164
      (46%) resolved additionally after reinjection. Thirteen (10%) of 133 Q-wave
      related defects showed filling-in at redistribution compared with 22 (27%) of 82
      remote defects (P = 0.001). After reinjection additional filling-in of defects
      was seen in 47 (39%) of 120 Q-wave related defects compared with 35 (58%) or 60
      remote defects (P = 0.015). Overall, 60 (45%) of 133 Q-wave related defects
      resolved compared with 57 (70%) of 82 remote defects (P = 0.005).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1396874
TI  - Thallium-201 single photon emission tomography of myocardium: additional
      information in reinjection studies is dependent on collateral circulation.
AB  - A second thallium-201 injection under resting conditions is able to improve the
      differentiation between myocardial scar and ischaemia when compared with simple
      redistribution imaging. The aim of this study was to evaluate the dependence of
      this improvement on the degree of stenosis and the presence of collaterals.
      Single photon emission tomography (SPET) studies under exercise, redistribution
      and reinjection conditions were performed on 84 patients with 181 stenotic
      vessels (70 left anterior descending, 47 left circumflex, 64 right coronary
      artery) and compared with angiography. An improvement of the 201Tl uptake in the
      reinjection image was observed in 53% of the myocardial areas served by a
      coronary artery with a stenosis of over 90%. This is compared with 13% of the
      areas served by a vessel with a stenosis between 50% and 90%. 90% of the
      collateralized areas showed a fill-in effect, but only 7 of the 118 without
      angiographically visible collateralization (6%). The dependence of the fill-in
      effect, collateralization and stenosis was highly significant (chi 2 test, p less
      than 0.0001). In our patient group, there was much greater benefit from the
      reinjection study in vessels with a greater than 90% narrowing. The fill-in
      effect was closely correlated to the presence of collaterals. In these cases, the
      fill-in may be an indication for hibernating myocardium.

PMID- 1396875
TI  - Prediction of reversible perfusion defects by quantitative analysis of post
      exercise electrocardiogram-gated acquisition of technetium-99m 2
      methoxyisobutylisonitrile myocardial perfusion scintigraphy.
AB  - The aim of this study was to assess the reliability of the quantitative analysis
      of regional wall thickening with electrocardiographic-gated technetium-99m 2
      methoxyisobutylisonitrile (SESTAMIBI) in predicting the reversibility of stress
      induced perfusion defects. The assumption was that a preserved resting wall
      thickening in a segment with stress-induced perfusion defect would predict normal
      resting perfusion. Twenty-five patients with suspected coronary artery disease
      underwent planar stress-rest SESTAMIBI scintigraphy. The wall thickening was
      quantitatively evaluated as percentage increase in counts from diastole to
      systole; a ratio defined as the wall thickening index (WTI) between patient and
      normal profile (mean - 2 SD) below 1 was considered abnormal. Improvement of the
      perfusion pattern at rest was observed in 76% (54/71) of segments with a stress
      induced perfusion defect; 90% of these segments had a (WTI) greater than 0.8.
      Five segments (9%) showed fixed perfusion defects despite a WTI value greater
      than 0.8. In conclusion, quantitative analysis of regional wall thickening by
      electrocardiographic-gated SESTAMIBI identifies segments with reversible
      perfusion defects; this may overcome the need for studies at rest and may direct
      the detection of hypoperfused but viable myocardium.

PMID- 1396876
TI  - Accuracy and repeatability of left ventricular systolic and diastolic function
      measurements using an ambulatory radionuclide monitor.
AB  - The accuracy and repeatability of a new ambulatory radionuclide detector (VEST)
      for left ventricular systolic (ejection fraction) and diastolic (peak filling
      rate) measurements were assessed. Seventeen patients underwent equilibrium
      radionuclide angiography immediately before and immediately after a VEST study.
      The accuracy was evaluated at the beginning and at the end of the VEST studies.
      Limits of agreement for the ejection fraction were -1%:2% at the beginning of the
      VEST study and -4%:4% at the end. Limits of agreement for the peak filling rate
      were -0.6:0.6 at the beginning of the VEST study and -0.7:0.5 at the end. For
      both measurements the limits of agreement were well within the clinical range.
      Repeatability was evaluated in a second group of 11 patients who underwent VEST
      studies in 2 separate days. The coefficient of repeatability (twice the standard
      deviation of the differences between the 2 studies) was 13 for the ejection
      fraction and 0.4 for the peak filling rate. Thus, the VEST is an accurate and
      repeatable method to measure both the ejection fraction and peak filling rate.

PMID- 1396877
TI  - The use of thallium-201 lung/heart ratios.
AB  - This survey gives an overview of the methodology of thallium-201 lung/heart
      uptake ratios often used as an independent factor in the assessment of patients
      with coronary artery disease undergoing myocardial perfusion scintigraphy.
      Different techniques have been used in the past. The most sensitive method is one
      which calculates a lung/heart ratio from scintigraphy obtained immediately after
      cessation of exercise. If single photon emission tomography (SPET) is routinely
      performed the anterior projection of the data set obtained during tomographic
      acquisition should be used in preference to a separate planar anterior static
      images recorded before or after the SPET procedure. The lung/heart ratio is
      useful as a prognostic indicator of outcome as it accurately mimics the degree of
      left ventricular dysfunction. With the increasing popularity of pharmacological
      stress testing there is evidence that this ratio still offer valid information.
      Additional work in this field is nevertheless required to further confirm this
      observation. In routine clinical practice, the lung/heart ratio should help and
      enable physicians to prioritise patients for urgent intervention.

PMID- 1396878
TI  - Scintigraphic quantitation of gastrointestinal motor activity and transport:
      oesophagus and stomach.
AB  - For the recognition and characterisation of oesophageal motor disorders,
      manometry represents the most reliable tool but yields no information on bolus
      transport. The transport can be quantitated by radionuclide techniques. The
      patient is positioned supine beneath a gamma-camera and instructed to swallow a
      radiolabelled bolus in a single gulp. Using a marker over the cricoid and the
      activity in the stomach as landmarks, regions of interest are drawn representing
      the upper, middle and lower third of the oesophagus and the gastric fundus.
      Activity-time curves enable one to recognise the clearance patterns in these
      regions. In combination, manometric and radionuclide transit studies recognise a
      higher number of motor disorders than either procedure alone. Radionuclide
      methods also are the most reliable and sensitive to quantitate gastric emptying.
      Procedure, meal size and composition as well as patient position must be
      standardised and correction techniques applied. The emptying of solid and liquid
      meal constituents can be evaluated concomitantly. Solids start to empty only
      after a lag phase of varying extent. With semi-solid meals, which are emptied at
      the same rate as solid meals of identical composition in the postlag phase, the
      recording time can be considerably shorter. Besides gastric emptying, the
      amplitude, frequency and propagation velocity of antral contractions can be
      recorded using serial images of short frame time and specially devised analytic
      techniques.

PMID- 1396879
TI  - A comparison of maximal exercise and dipyridamole thallium-201 planar gated
      scintigraphy.

PMID- 1396880
TI  - A simple method of estimating glomerular filtration rate.

PMID- 1396882
TI  - Short stature with normal growth hormone and elevated IGF-I.
AB  - We report on a Japanese girl with short stature, malar hypoplasia, up-slanting
      palpebral fissures, blue sclerae and thin, stiff and slightly brownish hair.
      Short stature started in utero and her psychomotor development was normal.
      Menarche appeared at 13 years 8 months. Height at 14 years 5 months was 132 cm (
      4.6 SD). Her growth hormone (GH) sleep pattern and responses to insulin, L-dopa,
      arginine, propranolol-glucagon and growth hormone-releasing hormone were normal.
      Plasma insulin-like growth factor I (IGF-I) was high (2170-4860 units/l) and
      increased from 4860 to 7080 units/l 20 h after biosynthetic GH injection. Gel
      infiltration patterns of the free and protein-bound IGF-I in plasma from the
      patient were not different from the controls; IGF-I fraction of the high and low
      molecular weight binding protein and the non-protein bound fraction were 75.5%,
      15.8% and 8.7%, respectively. IGF-I from the patient showed normal bioactivities
      when determined by [35S]sulphate and [3H]thymidine uptake into cultured rat
      chondrocytes, and by [3H]thymidine and [3H]alpha-aminoisobutyric acid uptake into
      the patient's skin fibroblasts. IGF-I binding to cultured skin fibroblasts from
      the patient was comparable to that of controls. These results suggest that tissue
      specific defects of IGF-I receptors may be the cause of increased IGF-I levels in
      the patient.

PMID- 1396881
TI  - Acute hydrops of the gallbladder in childhood.
AB  - Acute hydrops of the gallbladder (AHGB) is a rare paediatric disease being
      diagnosed with increased frequency due to its association with other illnesses
      and the availability of ultrasonography. The symptoms and signs of AHGB include
      abdominal pain, vomiting, abdominal mass and/or tenderness. As these clinical
      features mimic the more common surgical conditions such as acute appendicitis,
      intussusception and volvulus, some cases are still diagnosed only at laparotomy.
      Diagnosis is established by ultrasonography of the abdomen demonstrating normal
      biliary ducts and a distended gallbladder without calculi or congenital
      malformation. The aetiology of acute hydrops of the gallbladder is unknown but
      may be multifactorial. Treatment varies from non-operative management to surgical
      intervention.

PMID- 1396883
TI  - Upper gastro-intestinal tract bleeding in cirrhotic children candidates for liver
      transplantation.
AB  - Signs of portal hypertension, history of upper gastro-intestinal tract bleeding
      episodes and outcome of the latter were recorded in 76 cirrhotic children
      evaluated for liver transplantation. Fifty-three (70%) had varices and 22 (29%)
      had experienced upper gastro-intestinal tract bleeding. Of these 22, 19 bled from
      varices and 3 from ulcers. Non bleeding ulcers were also found in five patients
      bleeding from varices. Iterative sclerotherapy controlled acute variceal bleeding
      in all but one patient in whom emergency transplantation was performed. Six of
      the eight patients with ulcers were successfully treated by the H2 histamine
      receptor antagonist ranitidine. We conclude that iterative sclerotherapy is
      efficient to control acute variceal bleeding and prevents recurrent bleeding in
      children with end-stage liver diseases awaiting liver replacement. Bleeding
      asymptomatic ulcers are frequent and respond to H2 histamine receptor
      antagonists.

PMID- 1396884
TI  - A right lower quadrant mass in cystic fibrosis: a diagnostic challenge.
AB  - In a cystic fibrosis (CF) patient a right lower quadrant (RLQ) mass may be a
      difficult diagnostic problem. Most frequently it is due to a distal intestinal
      obstruction syndrome also called meconium ileus equivalent, but the possibility
      of intussusception and appendiceal abscess should also be considered. We describe
      three CF patients with an appendiceal abscess seen in a 4-year period. All three
      patients had a palpable RLQ mass. Chronicity and obliteration of the appendiceal
      lumen with abnormally viscid mucus may lead to concealed perforation and be
      responsible for the atypical presentation.

PMID- 1396885
TI  - Paraparesis secondary to a spinal mass as the presenting feature of
      erythroleukaemia in a 10-month-old child.
AB  - Severe neurological impairment as the first symptom of acute leukaemia is a
      rather uncommon finding. We report the case of a 10-month-old infant who
      presented with acute paralysis of the lower extremities due to cord compression
      by an epidural tumour composed of malignant erythrocyte precursor cells.
      Diagnosis of erythroleukaemia (EL) was made by needle biopsy of the spinal
      epidural mass and confirmed by bone marrow aspiration. Antileukaemic treatment in
      combination with radiotherapy to the epidural tumour led to haematological
      remission and neurological recovery with disappearance of the mass lesion as
      demonstrated by MRI. However, haematological relapse occurred with death of the
      patient 7 months after diagnosis. This is the first reported case of EL
      presenting with paraparesis due to an epidural tumour. The clinical symptoms,
      results of cytogenetic and immunological studies and the clinical course are
      described.

PMID- 1396886
TI  - Intracranial chordoma in a neonate.
AB  - We report the first case of a congenital intracranial chordoma. Hydrocephalus,
      sixth and seventh cranial nerve palsy, and torticollis were observed shortly
      after birth. The tumour was delineated by sonography, CT scans and MRI and the
      diagnosis confirmed after subtotal resection at the end of the newborn period.

PMID- 1396887
TI  - Disease patterns in early onset pauciarticular juvenile chronic arthritis.
AB  - A group of 76 children with early onset pauciarticular juvenile chronic arthritis
      (JCA) was studied in order to establish different disease patterns and to try and
      identify parameters associated with an unfavourable outcome. An intermittent
      pattern of disease was found in 60 children (79%). Of the remaining 16 patients
      continuous persistent pauciarticular disease activity was present in 7 (9.2%) and
      extended pauciarticular in 9 children (11.8%). An extended pauciarticular pattern
      was seen predominantly in children with continuous disease activity. It appeared
      to be impossible to predict the course of the disease on the basis of clinical
      parameters. The frequency of complications, such as local growth disturbances or
      psychosocial problems and of chronic anterior uveitis resulting in visual
      handicap correlated with continuous disease activity. The extended pauciarticular
      pattern, resulting in polyarthritis resembled seronegative polyarticular JCA,
      underlining previous reports that the joint pattern during the course of disease
      may be more important than joint pattern at onset of disease.

PMID- 1396888
TI  - Serious pertussis overlooked in infants.
AB  - Two infants with life-threatening pertussis are presented in whom the diagnosis
      was delayed. A review of pertinent literature suggests that the diagnosis of
      pertussis in infants is frequently missed and therefore the morbidity and
      mortality from this disease is underestimated.

PMID- 1396889
TI  - Exophiala dermatitidis pneumonia in cystic fibrosis.
AB  - The chest X-ray film of a girl with cystic fibrosis (CF) showed slowly increasing
      mottled densities during the 6th and 7th year of her life. Pulmonary symptoms and
      distress proceeded fast in spite of intensive treatment with antibiotics,
      corticosteroids, and physiotherapy. Three different fungal organisms were
      repeatedly cultured from the sputum: Candida albicans, Aspergillus fumigatus, and
      Exophiala dermatitidis. Antibodies against C. albicans were in the normal range.
      Candida antigen in blood and antibodies against A. fumigatus were absent.
      Antibodies against E. dermatitidis were detected by a recently developed indirect
      immunofluorescence assay. It seems most probable that E. dermatitidis was the
      causal agent for fungal pneumonia in this case. Under therapy with amphotericin B
      and flucytosine the clinical course and radiological appearance improved but
      definitive eradication of E. dermatitidis was only achieved after treatment with
      itraconazole. The isolation of this fungus from the sputum of a CF patient is
      reported for the first time. The significance of fungal infections in CF is
      discussed.

PMID- 1396890
TI  - Elastase alpha 1 proteinase inhibitor complex, granulocyte count, ratio of
      immature to total granulocyte count, and C-reactive protein in neonatal
      septicaemia.
AB  - In a prospective study elastase alpha 1-proteinase inhibitor (E alpha 1PI),
      polymorphonuclear (PMN) count, the immature to total neutrophil count ratio (I/T
      ratio), and C-reactive protein (CRP) were analysed in 74 patients (76 cases) with
      neonatal septicaemia at the time of initial clinical symptoms. At that early
      stage of the disease, 94% of the patients had abnormal values for E alpha 1PI,
      71% for I/T ratio, 61% for PMN count, and only 54% for CRP. PMN count was a poor
      indicator of septicaemia. Neutropenia, present in 26% of all patients, was
      related to normal E alpha 1PI in only 4 patients. The combined use of E alpha 1
      and I/T ratio was the most sensitive indicator. In all patients irrespective of
      causative bacteria or disease onset at least one of these parameters was
      elevated. In early-onset septicaemia (n = 31), normal CRP values occurred
      significantly more often (63%) than in late-onset sepsis (33%). Even in five of
      the seven fatal cases, initial CRP measurements were normal. The sensitivity of
      PMN count and I/T ratio did not differ significantly between early- and late
      onset septicaemia. Laboratory changes observed in 18 newborns during the first 3
      days of the septic episode show that the rate of pathological values for E alpha
      1PI and I/T ratio was highest at the time of initial clinical symptoms and
      decreased on days 2 and 3. In contrast, CRP reached maximal values as late as day
      2 (88% abnormal values), followed by a decrease on day 3. We conclude that the
      use of E alpha 1PI may improve the laboratory detection of neonatal septicaemia
      especially if used in combination with I/T ratio.

PMID- 1396891
TI  - Randomized double blind trial of Ambroxol for the treatment of respiratory
      distress syndrome.
AB  - In order to test the ability of Ambroxol to improve the clinical course of
      respiratory distress syndrome and to reduce the incidence of complications a
      multicentre, randomized, placebo-controlled double-blind trial was conducted.
      Entry was limited to infants with a birth weight below 1500 g. A total of 179
      neonates were enrolled, but 31 were later excluded because they had other
      diseases. Of the remaining 148 babies, 74 received Ambroxol (birth weight 1190 +/
      216 g; gestational age 29.1 +/- 1.9 weeks) and 74 placebo (birth weight 1168 +/-
      216 g; gestational age 28.9 +/- 1.9 weeks). In the Ambroxol group 23 (31%) and in
      the placebo group 27 (37%) infants died during the first 5 months of life. In 28
      day-survivors Ambroxol was able to significantly improve the PaO2/FiO2 ratio,
      mean airway pressure, phospholipid profile of tracheal effluent and pulmonary
      mechanics of spontaneously breathing infants. In addition, the incidences of
      bronchopulmonary dysplasia (29% vs 54%), intraventricular haemorrhage (25% vs
      44%) and postnatally acquired pneumonia (15% vs 36%) were significantly reduced
      in the Ambroxol group as compared to the control group. No adverse events
      attributed to the Ambroxol treatment were reported.

PMID- 1396892
TI  - Effect of dexamethasone on blood pressure--relationship to postnatal age.
AB  - The relationship of the change in blood pressure levels of very preterm infants
      treated with dexamethasone to postnatal age was investigated. Sixteen infants,
      median gestational age 26 weeks (range 23-33) (early treatment group), and 15
      infants, median gestational age 26 weeks (range 24-32) (late treatment group)
      were recruited. Dexamethasone was administered at a median postnatal age of 17
      days (range 3-26) and 50 days (range 29-112), respectively. The systolic blood
      pressure at the start of treatment and the maximum systolic blood pressure
      achieved during therapy were both significantly lower (P less than 0.01) in the
      early rather than the late treatment group. The change in blood pressure,
      however, that is, from the pre-treatment level to the maximum systolic blood
      pressure achieved during therapy, was similar in the two groups (median 38 mmHg,
      range 23-59 early treatment group and median 34 mmHg, range 16-66 late treatment
      group). We conclude that, even in the first 4 weeks of life, dexamethasone can
      cause a marked elevation of systolic blood pressure. As a consequence, regardless
      of the postnatal age at which dexamethasone is administered, blood pressure
      levels must be measured regularly.

PMID- 1396893
TI  - The relationship of fluid restriction during the 1st month of life to the
      occurrence and severity of bronchopulmonary dysplasia in low birth weight
      infants: a 1-year radiological follow up.
AB  - One hundred consecutive low birth weight (LBW) infants (less than 1751 g) were
      randomized into a study group having a restricted fluid intake until 4 weeks of
      age and a control group following the fluid regimen conventionally used in the
      hospital. Chest X-ray films were examined on admission, at the ages of 3 days, 7
      days, 2 weeks and 4 weeks and at 2-monthly visits to the outpatient clinic up to
      1 year of age or until the chest examinations were normal. The severity of
      hyaline membrane disease (HMD) and typical radiological abnormalities of
      bronchopulmonary dysplasia (BPD) were assessed. Twelve patients succumbed, one in
      the study group and 11 in the control group. The study group seemed experience
      less severe HMD than the controls. Fifty-four percent of the former and 32% of
      the latter were alive and had no radiological signs of BPD at 4 weeks of age (P
      less than 0.05). The difference between the groups in the cumulative number of
      normal chest X-ray examinations during the follow up was even more significant.
      The percentage of normal X-ray films at 1 year of age was 92% in the study group
      and 72% in the control group. These results suggest that fluid restriction for
      the first 4 weeks of life can lower the incidence of radiological abnormalities
      typical of BPD obtained during the 1st year of life in LBW infants. Pulmonary
      oedema seems to be a significant aetiological factor causing HMD to develop into
      chronic lung disease.

PMID- 1396895
TI  - Infectious and surgical complications of childhood continuous ambulatory
      peritoneal dialysis.
AB  - A 10-year retrospective study was performed with respect to the incidence of
      infectious and surgical complications in a young paediatric continuous ambulatory
      peritoneal dialysis population of 43 children (mean age 4.5 years [range 2.5
      months-15.8 years]). The incidence of infectious complications such as
      peritonitis and catheter-related infections correlated well with the results of
      other studies. A relatively high incidence of hernias (53%) was seen in our
      population, probably caused by the lower mean age of the children. Obstructions
      were caused by omental wrapping, peritonitis, or operative procedures and did not
      correlate with the period of catheter function. Early leakage occurred within 5
      days after catheter implantation. Later leakages were preceded by another
      complication, such as infection or obstruction. In early leakage, in contrast to
      later leakage, the catheter could be maintained.

PMID- 1396894
TI  - A 2-year follow up of babies enrolled in a European multicentre trial of porcine
      surfactant replacement for severe neonatal respiratory distress syndrome.
      Collaborative European Multicentre Study Group.
AB  - The postnatal growth, respiratory status and neurodevelopmental outcome of
      surviving babies enrolled in the first European multicentre trial of porcine
      surfactant (Curosurf) replacement for severe neonatal respiratory distress
      syndrome, were assessed at corrected ages of 1 and 2 years. Follow up rates of
      survivors were 93% at 1 year and 89% at 2 years. Treated and control groups were
      similar at both 1 and 2 years in terms of physical growth, the prevalence of
      persistent respiratory symptoms and the occurrence of major and minor disability.
      Serum antibodies recognising Curosurf and surfactant-anti-surfactant immune
      complexes were detected in both treated and control babies, the titres showing no
      difference between groups. Examination of histological lung sections from non
      survivors revealed a higher incidence of severe pulmonary interstitial emphysema
      in control babies than in those treated with surfactant. Surfactant treatment for
      severe respiratory distress syndrome reduces neonatal mortality and air leaks and
      is not associated with an increase in disability 2 years later.

PMID- 1396896
TI  - Evidence for intact V1-vasopressin receptors in congenital nephrogenic diabetes
      insipidus.
AB  - The binding of tritium-labelled arginine vasopressin to human platelet
      vasopressin receptors was investigated in patients with congenital nephrogenic
      diabetes insipidus. Binding characteristics, that is receptor affinity and the
      maximum number of binding sites, were not significantly different from those
      found in normal control individuals. The findings confirm the concept of intact
      V1 receptors in congenital nephrogenic diabetes insipidus. The defect in
      nephrogenic diabetes insipidus apparently only affects the cyclic adenosine
      monophosphate dependent V2 receptors.

PMID- 1396897
TI  - Tubular function and histological findings in ifosfamide-induced renal Fanconi
      syndrome--a report of two cases.
AB  - Two patients developed renal Fanconi syndrome (RFS) after intensive long-term
      chemotherapy for metastatic Ewing sarcoma and disseminated neuroblastoma. Whereas
      RFS was diagnosed in patient 1 before he developed osteomalacia, patient 2
      experienced severe rickets and growth retardation. Renal function studies
      revealed slight glomerular impairment and severe tubular defects leading to
      increased excretion of glucose, amino acids, inorganic phosphate and low
      molecular weight proteins, indicating proximal tubular damage. Patient 2
      additionally showed distal tubular dysfunction with acidosis and diminished
      concentrating capacity. Renal biopsy in patient 1 revealed marked proximal
      tubular defects without interstitial lymphocytic infiltration. In both patients
      renal damage could most likely be ascribed to previous ifosfamide (IFOS) therapy.
      Our patients showed no improvement in renal function after cessation of IFOS
      treatment, indicating a poor prognosis of once established RFS after IFOS
      therapy. Measurement of tubular reabsorption capacities provides exact
      information on the extent of tubular toxicity induced by IFOS and may be used to
      monitor IFOS treated patients.

PMID- 1396898
TI  - Airway obstruction in relapsing polychondritis: a case in childhood.

PMID- 1396899
TI  - Alkaptonuria detected by neuroblastoma screening system.

PMID- 1396900
TI  - Megadose methylprednisolone for diffuse infantile haemangiomatosis.

PMID- 1396901
TI  - Parvovirus B19 infection during pregnancy--an ongoing prognostic challenge.

PMID- 1396902
TI  - Granulomatous hepatitis.

PMID- 1396904
TI  - Joseph O'Dwyer (1841-1898).

PMID- 1396903
TI  - More evidence for hyperoxaluria in phosphate-treated X-linked familial
      hypophosphataemic rickets.

PMID- 1396905
TI  - Growth hormone treatment in Turner syndrome accelerates growth and skeletal
      maturation. Dutch Growth Hormone Working Group.
AB  - Sixteen girls with Turner syndrome (TS) were treated for 4 years with
      biosynthetic growth hormone (GH). The dosage was 4 IU/m2 body surface s.c. per
      day over the first 3 years. In the 4th year the dosage was increased to 6 IU/m2
      per day in the 6 girls with a poor height increment and in 1 girl oxandrolone was
      added. Ethinyl oestradiol was added after the age of 13. Mean (SD) growth
      velocities were 3.4 (0.9), 7.2 (1.7), 5.3 (1.3), 4.3 (2.0) and 3.6 (1.5) cm/year
      before and in the 1st, 2nd, 3rd and 4th year of treatment. Skeletal maturation
      advanced faster than usual in Turner patients especially in the younger children.
      Although the mean height prediction increased by 5.6 cm and 11 of the 16 girls
      have now exceeded their predicted height, the height of the 4 girls who stopped
      GH treatment exceeded the predicted adult height by only 0 to 3.4 cm.

PMID- 1396906
TI  - Gastrointestinal endoscopy in Henoch-Schonlein purpura.
AB  - Gastrointestinal (GI) endoscopy was performed in seven patients with Henoch
      Schonlein purpura (HSP). In two patients there were no cutaneous lesions at the
      time of endoscopy, but inflammation of the duodenum, especially of the second
      part, led to suspicion of the disease. Upper GI endoscopy showed abnormalities in
      six of seven cases, and sigmoidoscopy in one of four cases. The changes were more
      marked in the second part of the duodenum rather than in the bulb or the stomach.
      The endoscopic findings included redness, swelling, petechiae or haemorrhage,
      erosions and ulceration of the mucosa. Histology of the mucosal biopsy specimens
      revealed non-specific inflammation with positive staining for IgA in the
      capillaries, but failed to show vasculitis. Upper GI endoscopy, including study
      of IgA, can be useful in the diagnosis of HSP. Colonoscopy is less helpful,
      especially if limited to the sigmoid colon.

PMID- 1396907
TI  - Invasive aspergillosis complicating induction chemotherapy of childhood
      leukaemia.
AB  - Two children with acute leukaemia developed histologically confirmed invasive
      aspergillosis within 2 weeks after onset of polychemotherapy. One child had
      received only prednisone and one pulse of vincristine and daunorubicin before.
      This child showed classical roentgenographic signs of aspergilloma following an
      upper pulmonary lobe infiltration. The second patient developed caecal
      aspergillosis obscured by clinical signs of appendicitis. He died of disseminated
      aspergillosis several weeks later in spite of systemic antifungal therapy. Both
      case reports illustrate that the possibility of invasive aspergillosis must also
      be expected in young patients soon after onset of induction chemotherapy.

PMID- 1396908
TI  - The hepatic malignant mesenchymoma: a case report.
AB  - We report a case of hepatic mesenchymoma in an 8-year-old girl who presented with
      abdominal pain and ultrasonographic diagnosis of hepatic echinococcosis. Due to
      the good general condition of the patient and the diagnostic confirmation of
      liver hydatid disease by the CT scan, antiparasitic therapy with albendazole was
      started. After 1 month of therapy the girl's general condition worsened as did
      the ultrasonographic picture. On laparatomy a large cystic mass was observed
      within the right hepatic lobe and was removed. Pathological examination of the
      mass excluded an echinococcal cyst and demonstrated a malignant hepatic
      mesenchymoma.

PMID- 1396909
TI  - The inflammatory cytokines in measles: correlation between serum interferon-gamma
      levels and lymphocyte subpopulations.
AB  - Interleukin-1 (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and
      interferon gamma (IFN-gamma) were measured in serum from children with measles
      using an immunoradiometric assay. The IFN-gamma level was increased in 52 out of
      54 patients in the acute phase of measles (less than 7 days of illness), and then
      declined to an undetectable level in the convalescent phase. Neither IL-1 nor TNF
      could be detected during the course of the illness. The mean serum IFN-gamma
      level was at its peak on day 4 and could be detected over a 7-day period after
      the onset of fever, coinciding with the febrile period (6.9 +/- 1.5 days). In the
      acute phase, the phytohaemagglutinin responses, absolute number of platelets,
      total lymphocyte counts, CD3+, CD4+, CD8+ cell counts and the CD4/8 ratio were
      depressed, while stab cell number and lactate dehydrogenase levels were higher
      than those in the convalescent phase. Using Spearman rank sum test, the IFN-gamma
      level was correlated negatively with the peripheral lymphocyte (P less than
      0.01), CD3+ (P less than 0.05), CD4+ (P less than 0.05) cell counts and the CD4/8
      ratio (P less than 0.05) and correlated positively with the stab cell count (P
      less than 0.01) but not with any other parameter. When the acute phase findings
      were compared between 28 complicated and 40 uncomplicated patients, the former
      were younger (P less than 0.01) and had higher maximum body temperature during
      the illness (P less than 0.05) than the latter, there was no difference in their
      IFN-gamma levels. These results show that endogenous IFN-gamma appears in the
      circulation during the acute febrile phase of measles, but does not contribute
      directly to any complication of the disease.

PMID- 1396910
TI  - Pseudohyperkalaemia in Kawasaki disease.
AB  - Pseudohyperkalaemia was observed in 3 of 16 patients with Kawasaki disease
      showing remarkably increased platelet counts. Their plasma potassium
      concentration, which is not affected by in vitro coagulation, was in the normal
      range despite the increased serum level. A significant correlation was observed
      between the platelet count and the increase in the serum potassium level
      resulting from blood coagulation, which was estimated by subtracting the plasma
      potassium level from the serum level. This study indicates that
      pseudohyperkalaemia should be considered in patients with Kawasaki disease whose
      platelet counts are markedly increased.

PMID- 1396911
TI  - Plesiomonas shigelloides sepsis and meningoencephalitis in a neonate.
AB  - A newborn infant is described who presented with septicaemia and
      meningoencephalitis caused by Plesiomonas shigelloides, a Gram-negative rod
      belonging to the family Vibrionaceae. The patient in this case, the first to be
      documented in Europe, developed multilocular lysis of the brain despite immediate
      treatment with antibiotics active in vitro. A cranial CT revealed garland-like
      calcifications and a large amount of medullary necrosis was seen on MRI.

PMID- 1396912
TI  - Dipylidium caninum in an infant.
AB  - The tapeworm, Dipylidium caninum, occurs worldwide in dogs and cats. It may occur
      rarely in children, when the infection may be unrecognised or misdiagnosed. We
      report such a case.

PMID- 1396913
TI  - X-linked hydrocephalus: clinical heterogeneity at a single gene locus.
AB  - X-linked hydrocephalus-stenosis of the aqueduct of Sylvius sequence (H-SAS, MIM
      number 30007) is a rare genetic disorder characterized by hydrocephalus,
      macrocephaly, adducted thumbs, spasticity, agenesis of corpus callosum and mental
      retardation. We confirm here the localisation of the mutant gene on Xq (Xq 2.8)
      by linkage analysis in a 5-generation pedigree (maximum lod score of Z = 4.57 at
      theta = 0.04 with probe St14 at locus DXS52) and emphasise the phenotypic
      variability of the disease. Ventricular dilatation in affected males was either
      severe and diagnosed antenatally or moderate and consistent with a long survival
      with little or no macrocephaly. Since other X-linked syndromes of mental
      retardation with spasticity and flexion deformities of the thumbs have previously
      been shown to map to the Xq 2.8 region as well (e.g. MASA syndrome and spastic
      paraplegia), the present results raise the question of whether H-SAS syndrome,
      MASA syndrome and spastic paraplegia with mental retardation might represent
      different phenotypic expression of various mutations at the same locus.

PMID- 1396915
TI  - Psychological and social findings in adolescents with phenylketonuria.
AB  - In a retrospective study, 34 early treated, normally intelligent adolescents with
      phenylketonuria (PKU) and their parents were tested with several psychometric
      personality inventories and self-developed questionaires concerning their
      psychosocial situation and their disease- and diet-specific knowledge. Results
      show that the patients are characterized by less autonomy, a more negative
      evaluation of their scholastic ability, less achievement motivation, low
      frustration tolerance, more negative self description, less extraversion and
      impulsiveness, a feeling of not being quite healthy, more grave and a higher
      level of dependency from their families. The patients saw their whole social
      situation as being distinctly restricted. Their knowledge concerning disease and
      diet was alarmingly poor and the majority had great difficulties in managing the
      diet satisfactorily without parental help. Up to the age of 15 years the serum
      phenylalanine levels were persistently above the desired range.

PMID- 1396916
TI  - Is thoraco-abdominal phase relationship an indicator of sleep state?
AB  - The phase relationship between ribcage and abdominal movement in 1440 breaths
      from 12 infants (mean age 3.2 days) showed statistically significant differences
      between sleep states as judged by physiological criteria. The mean phase
      difference (+/- 1 SD) was 20 (+/- 16)% in active sleep, 9 (+/- 17)% in
      indeterminate sleep and 3 (+/- 5)% in quiet sleep (P less than 0.0005). However,
      the wide scatter within sleep states meant that even the mean value from 50
      breaths was not specific enough to delineate sleep state.

PMID- 1396914
TI  - Aplasia of the retinal vessels combined with optic nerve hypoplasia, neonatal
      epileptic seizures, and lactic acidosis due to mitochondrial complex I
      deficiency.
AB  - A newborn male with mitochondrial complex I deficiency suffered from neonatal
      epileptic seizures, which later developed into infantile spasms. The infant was
      blind due to aplasia of the retinal vessels and hypoplasia of the optic nerve.
      There was congenital lactic acidosis, which persisted in later life. The boy was
      microcephalic and retarded. Muscular hypotonia later shifted to spasticity.
      Succinic acid was increased in urine. We assume that the aplasia of the retinal
      vessels is due to damage of the retinal ganglion cells caused by the
      mitochondrial disease in the first 3 to 4 months of pregnancy.

PMID- 1396917
TI  - Ventilatory requirements for respiratory distress syndrome in small-for
      gestational-age infants.
AB  - Neonatal ventilatory requirements and outcome were examined in 135 very preterm,
      small-for-gestational age (SGA) infants to determine whether fetal growth
      retardation protects against severe respiratory distress syndrome (RDS) in very
      immature infants. Their results were compared to those from gestational age- and
      gender-matched controls. Although there was no significant difference in the
      median duration of mechanical ventilation between the two groups, more SGA
      infants required ventilation and were ventilated because of RDS. In a subgroup
      also matched for mode of delivery, there was no significant difference between
      the proportion of SGA infants requiring mechanical ventilation for RDS compared
      to their matched controls. The mortality was greater in the SGA group. We
      conclude that fetal growth retardation does not protect against severe RDS.

PMID- 1396918
TI  - Vacuum extraction, bone injury and neonatal subgaleal bleeding.
AB  - In a population of 27 flemish newborns with subgaleal bleeding encountered within
      a period of 6 years, we studied the obstetrical, clinical and radiological data.
      In contrast with controversial findings from the available literature, there is
      little doubt that difficult, often elective vacuum extraction is the main cause
      of this neonatal emergency. Disturbances in haemostasis, when documented, were
      attributed to focal intrahaematoma consumption, except for one boy who presented
      with haemophilia and neonatal subgaleal bleeding. Conventional X-ray examination
      continues to be of importance for the documentation of suture diastasis, fissures
      and fractures. CT scan reveals both the amount of extra-osseous bleeding, the
      degree of bone displacement and injury as well as the type and extent of
      associated intracranial damage. Subgaleal haemorrhage rarely hides a growing
      synchrondrosal rupture.

PMID- 1396919
TI  - Intraperitoneal administration of recombinant human erythropoietin in children on
      continuous ambulatory peritoneal dialysis.
AB  - In 16 children treated by continuous ambulatory peritoneal dialysis (CAPD)
      recombinant human erythropoietin was administered intraperitoneally for the
      treatment of renal anaemia. The mean treatment period was 8.3 months. Mean
      haemoglobin values increased from 4.9 mmol/l at start of therapy to 6.2 after 6
      months. While 11 out of 16 children needed a total of 22 transfusions during the
      6 months prior to therapy, no transfusions were needed after initiation of
      therapy. Patients started with a dose of 300 units/kg per week. After 6 months of
      therapy, the mean dose was 370 and after 12 months 279 units/kg per week. No
      major side-effects were observed. The incidence of peritonitis was not increased.
      We conclude that intraperitoneal administration of erythropoietin is effective in
      the treatment of renal anaemia in children treated by CAPD.

PMID- 1396920
TI  - Hypertension associated with skeletal traction in children.
AB  - Since traction-associated hypertension seems to be a relatively unknown
      phenomenon, a survey was done of its incidence in children treated with skeletal
      traction for fractures and orthopaedic diseases. The correlation with
      hypercalcaemia, a possible aetiological factor, was also explored. Blood pressure
      was recorded three times a day with an automatic oscillometric unit during the
      stay in the hospital. Serum calcium, creatinine and total protein concentrations
      were measured once a week. Patients with pre-existing diseases or renal trauma
      were excluded. Arterial hypertension (systolic and/or diastolic) was found in
      31/50 children (62%). In almost half of these the rise in systolic blood pressure
      was 10 mmHg or more above the 95th percentile. Hypertension occurred in most
      cases within the first 3 weeks of treatment; in 7 children it developed after 3
      or more weeks of traction. All children became normotensive within 1 week after
      discontinuation of traction. Clinical symptoms were rare: two children complained
      of headache. In no instance had traction to be discontinued before the planned
      date because of hypertension. In the hypertensive group were more preschool
      children and more humeral fractures as compared to the normotensive group (n =
      19). Hypercalcaemia occurred in 11 children and was equally distributed in
      hypertensive and in normotensive children. It is concluded that arterial
      hypertension is a frequent finding in children in traction, but its clinical
      relevance is uncertain. Hypercalcaemia is not a rare finding in immobilized
      children, but probably plays no causative role in traction-related hypertension.

PMID- 1396921
TI  - Dumping syndrome after combined pyloroplasty and fundoplication.

PMID- 1396922
TI  - C. Henry Kempe (1922-1984).

PMID- 1396924
TI  - Convulsions, hemiparesis and central retinal artery occlusion due to left atrial
      myxoma in child.
AB  - Multiple embolizations were the hallmark of the disease in an 8-year-old boy with
      a left atrial myxoma. Embolizations occurred initially in both hands and legs,
      later in the brain with generalized seizures and hemiparesis, and finally in the
      left eye with occlusion of the central retinal artery and consecutive severe
      visual impairment. Echocardiography demonstrated the tumour which was removed
      without complications.

PMID- 1396926
TI  - Solitary rectal ulcer: an unusual cause of rectal bleeding in children.
AB  - The solitary rectal ulcer syndrome (SRUS) is a disease which is commonly
      diagnosed in adults but only rarely described in children. Rectal prolapse and
      intussusception are frequently associated with this entity. A relationship
      between SRUS and chronic constipation due to spastic pelvic floor syndrome (SPFS)
      is often observed. Thus biofeedback defaecation training is an efficient
      treatment of both conditions. We describe two paediatric patients suffering from
      SRUS associated with SPFS who showed complete recovery after biofeedback
      defaecation training.

PMID- 1396925
TI  - The role of sonography in the evaluation of gastro-oesophageal reflux-
      correlation to pH-metry.
AB  - Sonography was compared to pH-metry and/or oesophagomanometry to evaluate the
      accuracy of sonography in the early diagnosis of gastro-oesophageal reflux.
      Thirty children with a mean age of 72 days (21-252 days) were studied. The
      results showed that specificity of sonographic diagnosis was 87.5% and
      sensitivity was 100% (with P less than 0.001). Sonography also proved helpful in
      providing both functional and morphological data in addition to pH-metric
      results. This study therefore suggests that sonography is useful as the first
      approach in the diagnosis of vomiting babies as it is non-invasive and provides
      sufficient diagnostic accuracy.

PMID- 1396927
TI  - Recombinant human erythropoietin in the treatment of infants with anaemia of
      prematurity.
AB  - Recombinant human erythropoietin (rHuEPO) was administered subcutaneously three
      times a week to 18 infants with the anaemia of prematurity at doses of 75, 150,
      300, or 600 units/kg per week for 4 weeks, starting at 3-4 weeks of postnatal
      age. A significant and dose-dependent increase in reticulocyte count was observed
      from a mean baseline value of 71 x 10(9)/l to 200 x 10(9)/l after 3 weeks of
      therapy, compared with a change from 69 to 97 x 10(9)/l in 66 historical
      controls. The haematocrit value remained unchanged during rHuEPO treatment,
      whereas it steadily declined until 9 weeks of postnatal age in the controls.
      These effects were accompanied by a marked reduction in serum iron concentration
      and transferrin saturation in patients receiving standard-dose iron supplements,
      but not in those given larger doses. Only 3 of 18 patients required a red blood
      cell transfusion. These infants were among the most anaemic at entry into the
      study and 2 of them were unable to complete rHuEPO therapy, while the third
      developed iron deficiency anaemia. These data indicate that rHuEPO with
      appropriate iron supplementation may accelerate the recovery from anaemia of
      prematurity. Larger scale placebo-controlled studies are now needed to confirm
      these findings and verify their impact on transfusion requirements of premature
      infants.

PMID- 1396929
TI  - Complement component deficiencies and infection: C5, C8 and C3 deficiencies in
      three families.
AB  - Three families are described with complement component deficiencies. In one
      family, five children had C5 deficiency; in a second family, two children had C8
      deficiency and one child in a third family had C3 deficiency. The index cases
      were identified during screening of patients with recurrent pyogenic infections,
      recurrent meningitis and meningococcaemia. Two of the five C5 deficient patients
      had recurrent meningitis and meningococcaemia, two had recurrent respiratory
      tract infections and otitis and one was healthy. One of the C8 deficient patients
      had meningitis, meningococcaemia and pneumonia, whereas his sibling with the same
      deficiency was healthy. The patient with C3 deficiency had four episodes of
      meningitis and recurrent otitis.

PMID- 1396928
TI  - May-Hegglin anomaly: a rare cause of thrombocytopenia.
AB  - A family with four and an unrelated family with three individuals affected by the
      May-Hegglin anomaly are described. Platelet counts were markedly reduced and were
      correctly determined only in the counting chamber. Bleeding time and platelet
      aggregation were always normal, but platelet nucleotide concentrations (ATP and
      ADP) were elevated. The platelet glycoprotein complexes Ib/IX, IIb/IIIa and
      Ia/IIa were quantitatively normal. Platelet-associated IgG was slightly elevated,
      although thrombocytopenia was presumably not caused by an immunological
      mechanism. Morphological investigations showed giant platelets and spindle-shaped
      inclusion bodies in the granulocytes, while their function (phagocytic capacity,
      radical production) was normal. To exclude hereditary types of thrombocytopenia,
      morphological and family investigations are required to avoid misdiagnosis with
      far-reaching diagnostic and therapeutic consequences.

PMID- 1396923
TI  - The respiratory syncitial virus and its role in acute bronchiolitis.

PMID- 1396930
TI  - Defective B-cell and regulatory T-cell function in Wiskott-Aldrich syndrome.
AB  - We report two Chinese boys with Wiskott-Aldrich syndrome presenting with gastro
      intestinal bleeding, eczema and recurrent infection. They had thrombocytopenia
      and the mean platelet volume was small. Serum IgG and IgA were elevated and
      lymphocyte proliferation in response to phytohaemagglutinin, concanavalin A and
      pokeweed mitogen was defective. Despite documented herpes simplex virus type 1
      and cytomegalovirus infection in one patient, he did not mount any humoral
      response. The generation of antibody-secreting cells in response to pokeweed
      mitogen was markedly defective in a plaque-forming cell assay. Both patients'
      regulatory T-cell and B-cell functions were defective in this assay. The genetic
      defect in Wiskott-Aldrich syndrome therefore affects T-cells, B-cells and
      platelets.

PMID- 1396931
TI  - Influence of the development of diabetes mellitus on clinical status in patients
      with cystic fibrosis.
AB  - The impact of pre-diabetes on clinical status was retrospectively studied in 38
      cystic fibrosis (CF) patients with diabetes mellitus (DM) and 38 non-diabetic CF
      patients (control patients), matched in pairs for age, sex, and chronic
      Pseudomonas aeruginosa lung infection. Quarterly parameters of CF clinical status
      were collected for 6 years prior to the diagnosis of DM in the index case.
      Compared to the control patients, decreases in body weight, body mass index
      (BMI), forced expiratory volume in 1s (FEV1), and forced vital capacity (FVC) and
      an increase in the daily intake of pancreatic enzyme capsules were found in the
      pre-diabetic patients. Statistically significant differences in body weight, BMI,
      FEV1, FVC, and intake of pancreatic enzyme capsules between pre-diabetic and
      control patients emerged 4, 4, 1.25, 3 and 4.5 years prior to the diagnosis of
      DM, respectively. The number of lung infections did not differ between the two
      groups of patients. Thus, when DM develops in CF patients, an insidious decline
      in overall clinical status is observed for years prior to its diagnosis. Whether
      clinical deterioration in CF leads to DM, or pre-diabetes results in declining CF
      clinical status is presently unknown. Accumulating evidence suggests that the
      latter may be the case since insulin therapy seems to improve lung function in
      CF.

PMID- 1396933
TI  - Neonatal complications of extreme prematurity in mechanically ventilated infants.
AB  - Previous data have suggested that neonatal complications amongst preterm
      ventilated infants increase with decreasing gestational age and thus are likely
      to be greatest among ventilated infants of less than 28 weeks gestational age.
      The aim of this study was to test that hypothesis, thus we report the neonatal
      complications of 175 extremely preterm mechanically ventilated infants
      (gestational age less than or equal to 28 weeks). Of the infants 152 were
      ventilated because of respiratory distress syndrome (RDS) or respiratory distress
      of severe prematurity, 41% of these infants died. Amongst infants with RDS or
      respiratory distress of extreme prematurity, mortality was significantly
      increased in infants of gestational age less than or equal to 24 weeks and birth
      weight less than or equal to 1000 g. In this group 20% developed a pneumothorax,
      and mortality was inversely related to gestational age. In infants with RDS, 43%
      developed a periventricular haemorrhage and 37% were still oxygen-dependent at 28
      days of age; neither of these complications was significantly related to birth
      weight or gestational age. Of infants with RDS 38% developed a patent ductus
      arteriosus and 16% developed retinopathy of prematurity. These data suggest that
      even amongst very immature infants there has been an impressive reduction in the
      neonatal complications of mechanical ventilation.

PMID- 1396932
TI  - Complement fragment C3a in plasma of asphyxiated neonates.
AB  - Recent clinical studies with adult polytrauma patients indicate that elevated
      plasma levels of anaphylatoxin C3a correlate with the subsequent development of
      the adult respiratory distress syndrome (ARDS). However, there are no parameters
      which allow a reliable diagnosis of ARDS in neonates. As the most predisposing
      condition for ARDS seems to be shock, plasma C3a was determined in 30 ventilated
      premature infants and neonates with respiratory distress syndrome (birth weights
      660-3350 g) within the first 24 h post partum or 6-24 h after acute asphyxia or
      shock during the neonatal period. The range of C3a, measured by ELISA, was
      between 57 and 1000 ng/ml. In the asphyxia group (n = 15) peak levels of C3a in
      plasma (mean 388 ng/ml) were significantly higher (P less than 0.001) than in the
      control group (mean 153 ng/ml). In some neonates with suspected ARDS, additional
      samples were taken. A rise in C3a between days 2 and 8 was associated with a
      fatal outcome of the disease. As in adults, C3a might be a useful indicator for
      ARDS in neonates.

PMID- 1396934
TI  - Acute deteriorations in neonatal chronic lung disease.
AB  - Preterm infants with chronic lung disease (CLD) have frequent respiratory
      relapses. The aim of this study was to assess the aetiology of such
      deteriorations and in particular the proportion due to viral infections. During
      the study period 118 preterm infants with birth weight less than 1500 g were
      consecutively admitted to the neonatal intensive care unit; 22 (18.6%) developed
      CLD. At the onset of all respiratory deteriorations, infants were examined for
      the presence of patent ductus arteriosus, apnoea or aspiration; they were also
      carefully screened for both viral and bacterial infection. The 22 infants had a
      total of 74 episodes of respiratory deterioration; median 3 per baby (range 1-8).
      Two episodes were associated with patent ductus arteriosus, 18 with apnoea and 5
      with aspiration. Infection was suspected or proven in association with all other
      episodes. On ten occasions the infants had positive blood cultures and on a
      further eight, bacteria were isolated only from the endotracheal or
      nasopharyngeal secretions. On the remaining 31 occasions, 27 associated with
      chest X-ray film abnormalities, infection was suspected, but no bacteria
      isolated. Viral infections were identified in association with 8 (11%) of these
      episodes. We conclude viral infection should be considered as a cause of
      otherwise unexplained respiratory deteriorations in infants with neonatal CLD.

PMID- 1396935
TI  - Energy and nutrient intake of patients with mild-to-moderate chronic renal
      failure compared with healthy children: an Italian multicentre study.
AB  - Nutritional counselling is important in the management of children with chronic
      renal failure (CRF). In 1988, a controlled European multicentre study was started
      to evaluate the effects of a low-protein diet on the progression of CRF in
      children. To assess the energy, macro- and micronutrient intake, 4-day weighed
      dietary records were obtained from 50 children with low to moderate CRF
      (creatinine clearance 65 to 15 ml/min per 1.73 m2) and from 93 healthy children.
      The mean energy intake was 90%-93% of the recommended dietary allowance for
      Italian children in controls and 76%-88% in CRF patients. The mean protein intake
      was 2.1-3.1 g/kg per day in controls and 1.6-2.7 g/kg per day in CRF patients.
      Overall, the energy intake was 10% and the protein intake 33% lower in CRF
      patients than in healthy children. Children with CRF consumed less cholesterol,
      calcium and phosphorus than healthy children. The lower spontaneous intake of
      energy, protein and other nutrients should be taken into account when planning
      the nutrition of children with CRF.

PMID- 1396937
TI  - Diagnosis of intralobar lung sequestration by colour-coded Doppler sonography.
AB  - Intralobar lung sequestration in a 5-month-old dyspnoeic infant was diagnosed by
      colour-coded Doppler sonography (CDS). Grey scale imaging showed an echogenic
      mass adjacent to the right hemidiaphragm. CDS demonstrated an abnormal arterial
      blood supply via a vessel originating from the descending aorta at the level of
      the diaphragm.

PMID- 1396936
TI  - Intracranial blood flow velocities during seizures and generalized epileptic
      discharges.
AB  - In 51 children with different types of epilepsy, blood flow velocities in the
      middle cerebral artery were recorded continuously by transcranial Doppler
      sonography during a standard electroencephalogram of 30 min duration. In 16
      children 33 epileptic seizures were recorded. During tonic seizures, the mean
      flow velocity increased to a maximum of 133%-191% (median 160%) of the baseline
      values. Tonic-clonic seizures were also accompanied by a velocity increase.
      During absence seizures the mean flow velocity decreased to a minimum of 46%-82%
      (median 71%) of the baseline values. Changes in cerebral metabolism and arterial
      blood pressure in the presence of disturbed autoregulation are thought to be
      factors causing these alterations. No alteration of the flow velocities occurred
      in cases of petit-mal status, electrical status epilepticus and in 35 children
      with generalized epileptic discharges of up to 5 s duration without clinical
      manifestations.

PMID- 1396938
TI  - Severe hepatorenal failure in a child receiving carbamazepine and erythromycin.

PMID- 1396939
TI  - Dup 3(q) syndrome and neuroblastoma.

PMID- 1396940
TI  - Unilateral leg cyanosis: an unusual complication of circumcision.

PMID- 1396941
TI  - Optimal BCG treatment of superficial bladder cancer as defined by American
      trials.
AB  - Immunotherapy provides an effective alternative approach to chemotherapy in the
      management of superficial bladder cancer. The first widely used immunotherapy,
      bacillus Calmette-Guerin (BCG), eradicates residual tumour bacillus Calmette
      Guerin (BCG), eradicates residual tumour in one half of patients with carcinoma
      in situ. Unlike chemotherapy, induction of immunity against transitional cell
      carcinoma has the potential of protecting patients from tumours which have not
      yet developed. Controlled trials suggest that BCG immunotherapy reduces disease
      progression, decreases the need for cystectomy and prolongs survival. While the
      optimal BCG treatment schedule remains unknown and may in fact vary from one
      patient to another, data clearly suggest that a single 6-week induction course is
      suboptimal. In 150 randomized patients with CIS treated with 120 mg Connaught
      BCG, Southwest Oncology Group (SWOG) investigators found that just 3 additional
      weekly treatments at week 12 increased complete response from 70 to 82% (p less
      than 0.05). Intravesical BCG is clearly superior to oral BCG, and controlled
      studies have demonstrated that percutaneous administration is not necessary.
      While evidence suggests that BCG is the best available treatment for superficial
      bladder cancer and 95% of patients have no significant toxicity, serious and even
      fatal toxicity can occur. Sepsis can occur with intravenous absorption and often
      appears to result from hypersensitivity. Limited clinical and animal model
      experience suggests that cycloserine improves survival over treatment with
      isoniazid and rifampicin, but optimal treatment of BCG sepsis is isoniazid 300
      mg, rifampicin 600 mg, and prednisolone 40 mg daily.

PMID- 1396942
TI  - Role of the immune response in BCG for bladder cancer.
AB  - Intravesical bacillus Calmette-Guerin (BCG) has been shown in prospective,
      randomized clinical trials to be the treatment of choice for superficial bladder
      cancer. In this treatment regimen, viable bacteria are introduced into the
      bladder, provoking an infection which induces the immunological response that
      initiates antitumour activity. The role of T-lymphocytes and the T-lymphocyte
      subsets, helper T cells (Th) and cytotoxic T-cells (Tc) in the antitumour
      response has been evaluated. Depletion of total T, Th or Tc subsets in mice
      eliminated BCG-mediated antitumour activity. Delayed type hypersensitivity was
      abrogated only in Th-depleted mice, but the presence of Th-mediated delayed-type
      hypersensitivity (DTH) was not sufficient for expression of BCG-mediated
      antitumour activity. There was no evidence for the induction of protective
      immunity to the tumour after BCG therapy. These results show that T-lymphocytes
      are required for BCG-mediated antitumour activity and suggest that the antitumour
      activity mediated by BCG is of a nonspecific immunological type. No specific
      tumour cell immunity was detected.

PMID- 1396943
TI  - From the 19th to the 21st centuries: BCG in the treatment of superficial bladder
      cancer.
AB  - In superficial bladder cancer, bacillus Calmette-Guerin (BCG) is effective in the
      prevention of tumour recurrences, in the destruction of papillary lesions and,
      particularly, in the eradication of carcinoma in situ. In comparative trials BCG
      is superior to chemotherapeutic agents. Recent statistics indicate that though
      the incidence of bladder cancer continues to increase, the mortality has begun to
      diminish. The use of BCG has been implicated as an important contributor to this
      change. The exact mechanisms of action of this anticancer agent remain obscure,
      but clarification should lead to the development of new, safer and more effective
      agents. Thus, BCG, an anachronism from the early days of tumour immunology, may
      lead cancer immunotherapy into the next century.

PMID- 1396945
TI  - BCG for carcinoma in situ.
AB  - Bacillus Calmette-Guerin (BCG) is the most effective intravesical therapy of
      carcinoma in situ of the urinary bladder. Six, weekly instillations of BCG result
      in a complete remission in about 70-80% of patients. The optimal dose however has
      still to be defined, and the value of maintenance therapy is also a matter of
      debate. Recurrent tumours after complete remission occur mainly in the distal
      ureter and prostatic urethra. In these patients, cystectomy may be required. In
      about 60-80% of patients, local (e.g. cystitis) and/or systemic (e.g. fever,
      malaise) side effects are observed. The occurrence of cystitis is associated with
      the number of instillations, BCG dose and a positive skin test. Systemic side
      effects are connected with pre-existing dysuria or bacterial cystitis and with
      traumatic catheterization. Severe toxicity occurs in about 5% of the patients.
      Prognostic parameters indicating complete remission have yet to be determined,
      but there is evidence that cytokines detected in the urine and immune-cell
      infiltration into the bladder wall revealed by immunohistochemistry, can be of
      value in this respect.

PMID- 1396944
TI  - Prospects for improving the efficacy of BCG.
AB  - Since 1976, when Morales, Eidinger and Bruce first published on the treatment of
      human urothelial bladder cancer, bacillus Calmette-Guerin has gained worldwide
      acceptance as a therapy against bladder carcinoma recurrences. However, there are
      many uncertainties with regard to patient selection, treatment protocol,
      reduction of side effects, mechanisms of action, and thus room enough for
      laboratory researchers and clinicians to contribute to the improvement of BCG
      therapy. Initiation of mycobacterial binding to urothelial cells may be promoted
      by methods which increase fibronectin exposure on target cells, reduce inhibitory
      factors in the instillate, or by identification of more avidly binding substrains
      of BCG. Quantification of the ensuing immune response focuses on the local rather
      than the systemic immune reaction of the host and may give the opportunity to
      predict a favourable response, or even the endpoint of therapy. For this purpose,
      assessment of local cytokine production seems to be a valuable tool. Ultimately,
      revealing the mode of action(s) of live BCG may render the use of potentially
      dangerous live bacilli unnecessary and lead to the application of derivatives
      with better results.

PMID- 1396946
TI  - BCG therapy in superficial bladder tumours--complications and precautions.
AB  - Bacillus Calmette-Guerin (BCG) immunotherapy represents a valuable treatment in
      the management of superficial bladder cancer, but the therapy is not without its
      risks. A total of 220 patients have been included in a review of local and
      systemic side effects associated with BCG immunotherapy. The majority of side
      effects are mild and self limiting, but potentially life threatening
      complications can arise with BCG immunotherapy. These systemic side effects
      include pneumonitis/hepatitis and systemic BCG infection. Recommendations are
      given for the use and administration of BCG, and if these rules are correctly
      applied, BCG may be administered safely, and with confidence.

PMID- 1396948
TI  - Development and preliminary psychometric properties of the Transition Competence
      Battery for Deaf Adolescents and Young Adults.
AB  - This article describes the development and preliminary psychometric properties of
      the Transition Competence Battery for Deaf Adolescents and Young Adults (TCB).
      The TCB includes three subtests on employment and three subtests on independent
      living, in a 3-option multiple-choice format and with both written and videotaped
      instructions. The TCB was standardized on students from both mainstreamed and
      residential settings (n ranged from 180 to 230 for the different subtests).
      Overall, the item statistics and subtest reliabilities were adequate. An initial
      study of the battery's construct validity was conducted. Results demonstrated the
      power of all of the TCB subtests to differentiate among various groups.

PMID- 1396947
TI  - BCG in superficial bladder cancer: a review of phase III European trials.
AB  - Shortly after Morales' original report, several phase II trials confirmed the
      effectiveness of intravesical bacillus Calmette-Guerin (BCG) in superficial
      bladder cancer therapy. Concerns have been expressed about the toxicity related
      to this new therapeutic modality. These phase II trial data led European
      urologists to try to answer some questions related to BCG therapy, such as the
      optimal schedule and dose, the most effective BCG strain and the value of BCG
      compared with current chemotherapeutic drugs. To date, phase III trials have
      shown that BCG is more effective than thiotepa and doxorubicin in reducing tumour
      recurrences and progression and that BCG seems to be as effective as mitomycin C.
      Toxicity is significantly higher with BCG compared to chemotherapeutic drugs; no
      strain of BCG seems to be superior in this respect. Further studies are required
      to identify the optimal schedule and dose, as well as the best therapeutic
      efficacy/toxicity ratio.

PMID- 1396949
TI  - Making sense of disability: low-income, Puerto Rican parents' theories of the
      problem.
AB  - This article reports findings from an ethnographic study of the views of 12 low
      income Puerto Rican parents whose children were classified as learning disabled
      or mildly mentally retarded. Different cultural meanings of disability and
      normalcy led parents to reject the notion of disability and focus on the impact
      of family identity, language confusion, and detrimental educational practices on
      children's school performance. Parents' views were in line with current arguments
      against labeling and English-only instruction.

PMID- 1396950
TI  - Implementing a successful writing program in public schools for students who are
      deaf.
AB  - A 2-year project to improve the writing skills of children who are deaf included
      instruction for teachers in the process approach to teaching writing. The project
      encompassed 10 public school programs for students who are deaf and included 325
      students in Grades 4-10 and 52 teachers. The project included specific training
      goals for teachers, a self-report procedure for the teachers, and a data
      collection and analysis phase to assess short-term effects on students' writing.
      Teacher self-reports indicated widespread involvement in the project, and pretest
      and posttest results showed dramatic improvement in students' writing-
      particularly in grammatical skills. Scoring systems for students' papers are
      included.

PMID- 1396951
TI  - The Task Demonstration Model: a concurrent model for teaching groups of students
      with severe disabilities.
AB  - This study investigated the use of the Task Demonstration Model (TDM) of group
      instruction for students with severe or moderate retardation. This model and the
      Standard Prompting Hierarchy (SPH) were tested against each other (and baseline)
      across three teachers and groups of students. Results on teacher variables showed
      that demands and praise were roughly equivalent for both procedures, but prompts
      were 12 times higher in SPH than in TDM. Data on student variables showed task
      engagement to be the same for SPH and TDM, percent correct to be 10% higher in
      TDM, but rate correct to be twice as much in TDM as in SPH.

PMID- 1396952
TI  - Grading secondary vocational education students with disabilities: a national
      perspective.
AB  - A nationwide purposive sample of secondary vocational educators completed a
      questionnaire that examined practices and perceptions toward grading students
      with disabilities. A variety of grading methods was reportedly used, but over two
      thirds of respondents included a competency-based grading component. An
      overwhelming majority believed that student effort should be used to determine
      grades. Two-thirds of vocational educators had never been involved in their
      students' IEP development. The most common changes teachers have made over time
      in their grading practices included becoming more flexible and individualized in
      grading. Overall, teachers displayed moderately positive attitudes toward grading
      students with disabilities.

PMID- 1396953
TI  - Teaching children with autism through task variation in physical education.
AB  - The purpose of the study was to determine whether the technique of task variation
      (with maintenance tasks interspersed) (TV) is more effective in the acquisition
      of gross motor skills for students with autism than a constant task (CT)
      condition in a physical education setting. Subjects were 12 male students with
      autism, ages 11 to 15 years. The study included pretest-posttest administration
      of the I CAN assessment of Gross Motor Skills to assess skills such as overhand
      throw, kick, and vertical jump. After a 6-week treatment period, the TV condition
      was significantly more effective than the CT condition, at the .05 level.

PMID- 1396954
TI  - Biochemical evidence of the physical association of the majority of CD3 delta
      chains with the accessory/co-receptor molecules CD4 and CD8 on nonactivated T
      lymphocytes.
AB  - The association of components of the CD3 complex with the accessory molecules CD4
      and CD8 was studied by immunoprecipitation experiments followed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. Enhanced surface
      iodination was achieved by a water-soluble derivative of the Bolton-Hunter
      reagent. Using freshly isolated nonactivated splenic T cells, we find that
      antibodies to CD4 and to CD8 strongly co-precipitate a 28-30-kDa band identical
      in mobility to the delta chain of the CD3 complex. Components corresponding in
      mobility to the epsilon and gamma chains of the CD3 complex are also co
      precipitated but to a much lesser extent. The identity of the co-precipitated 28
      30-kDa material with the CD3 delta chain was ascertained by two-dimensional
      nonreducing/reducing SDS-PAGE, by two-dimensional non-equilibrium pH gradient
      electrophoresis/SDS-PAGE and by one-dimensional peptide mapping with three
      different proteases. The co-precipitated 28-30-kDa material was identical to the
      CD3 delta chain by all these criteria. Quantitative analyses by densitometric gel
      tracing revealed that the amounts of CD3 delta co-precipitated with anti-CD4 and
      anti-CD8 add up to those in anti-V beta precipitates and to an average of 90% of
      those in anti-CD3 epsilon precipitates. We conclude that the majority of CD3
      delta chains are associated with the accessory/co-receptor molecules CD4 or CD8
      on resting T cells, and that this association is independent of antigen-specific
      recognition by the T cell receptor.

PMID- 1396955
TI  - Improved survival from potentially lethal graft-vs.-host disease by donor
      pretreatment with a recipient-specific blood transfusion. I. Requirements for
      induction and specificity of the effect.
AB  - Pretreatment of prospective donors of hemopoietic cells with a single recipient
      specific blood transfusion can significantly decrease the morbidity and mortality
      of graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically
      reconstituted mice. This beneficial effect of donor pretreatment could be
      demonstrated in donor-recipient strain combinations that were H-2 + non-H-2, H-2,
      or only class II-disparate, but not in the class I-disparate C57BL-B6.C-H-2bm1
      strain combination. The effect was proportional to the amount of recipient-strain
      blood used for transfusion. Donor transfusion with a single dose of 1 ml
      recipient-specific whole blood resulted in minimum GVHD, lower doses being less
      or not effective. The interval between donor pretreatment and the use of their
      hemopoietic cells for reconstitution appeared to be important. The best survival
      was found at an interval of 4 days. Multiple transfusion was not more effective
      than a single one. We compared the effectiveness of whole blood and irradiated
      spleen cells for donor pretreatment. Both protocols have been shown previously to
      suppress anti-recipient delayed-type hypersensitivity. It appeared that the blood
      transfusion protocol was superior to the spleen cell protocol. The beneficial
      effect appeared to be recipient specific, since a third-party blood transfusion
      did not improve GVHD. We found that the beneficial effect of donor blood
      transfusion was due to suppression of the anti-host immune response. The donor
      blood transfusion was able to induce bystander suppression to alloantigens that
      were not used for the induction of suppression, provided they were co-expressed
      with the specific alloantigens by the recipients. This also indicates that,
      although the induction of suppression is specific, the ultimate suppressive
      effect is non-specific.

PMID- 1396956
TI  - Inhibition of human immunodeficiency virus infection in human colon epithelial
      cells by recombinant interferon-gamma.
AB  - Pretreatment of human colon epithelial cells HT29 by recombinant gamma interferon
      (IFN)-gamma was found to protect the cells from infection with various isolates
      of human immunodeficiency virus (HIV)-1 and HIV-2, as assessed by co-cultivation
      with human T lymphoblastoid cells and gene amplification by polymerase chain
      reaction technique. Additionally, IFN-gamma induced a dose-dependent inhibition
      of HIV-1 and HIV-2 production in chronically infected HT29 cells. In situ
      hybridization studies demonstrated that IFN-treated cells were still able to
      synthesize viral messenger ribonucleic acid. However, the expression of the p24
      product of the gag gene was markedly decreased after IFN treatment as
      demonstrated by radio-immunoprecipitation assay. Taken together, these data
      suggested that the cytokine acted at the post-translational level by inhibiting
      the processing of structural viral proteins. It is concluded from this study that
      IFN-gamma has a potent anti-HIV effect on epithelial gastrointestinal cells.

PMID- 1396957
TI  - The microbicidal activity of interferon-gamma-treated macrophages against
      Trypanosoma cruzi involves an L-arginine-dependent, nitrogen oxide-mediated
      mechanism inhibitable by interleukin-10 and transforming growth factor-beta.
AB  - The present study was carried out to determine the effector mechanism of anti
      Trypanosoma cruzi activity by interferon (IFN)-gamma plus lipopolysaccharide
      (LPS)-treated macrophages. A macrophage cell line (IC-21) that failed to mount an
      appreciable oxidative burst was nevertheless found able to control T. cruzi
      growth after exposure to IFN-gamma alone or IFN-gamma plus LPS. Moreover,
      microbicidal functions of both inflammatory macrophages and IC-21 against T.
      cruzi was found to be inhibited in the presence of NG-monomethyl-L-arginine
      (NGMMA), a competitive inhibitor of L-arginine. Addition of supplemental L
      arginine to the culture overcame the capacity of NGMMA to block activated
      macrophage anti-T. cruzi functions. The ability of NGMMA to reverse both parasite
      growth inhibition and killing by IFN-gamma plus LPS-activated macrophages was
      found to correlate with the suppression of nitrite accumulation in the culture
      supernatants. Together, these results implicate the L-arginine-dependent
      production of nitric oxide in T. cruzi killing by activated macrophages. We also
      tested the ability of interleukin(IL)-10 and transforming growth factor (TGF)
      beta, to block regulation of T. cruzi growth in this system. Both IL-10 and TGF
      beta inhibited anti-parasite function by IFN-gamma-activated macrophages, with an
      optimal dose of 100 units/ml and 0.5 ng/ml, respectively. Moreover, when used in
      combination, suboptimal doses of IL-10 and TGF-beta were found to produce a
      synergistic inhibitory effect in the regulation of T. cruzi growth. The ability
      of IL-10 and TGF-beta to suppress microbicidal function was also positively
      correlated with inhibition of nitrite generation in macrophage culture
      supernatants. These results predict an in vivo role for IL-10 and TGF-beta in
      promoting parasite survival in the face of the host cell-mediated immune
      response.

PMID- 1396958
TI  - Membrane region of surface IgM is not sufficient for transducing growth
      inhibitory signals in an immature B cell line WEHI-231.
AB  - The murine B lymphoma line WEHI-231 is representative of immature B cells. Like
      normal immature B cells, WEHI-231 is susceptible to growth arrest following cross
      linking of surface IgM (sIgM). Previously, we have shown using a WEHI-231
      immunoglobulin (Ig) delta-transfectant that sIgD cross-linking failed to initiate
      growth arrest, in contrast to sIgM. In this report, we extend our research to
      investigate the structural requirement of Ig mu chain for regulating growth
      inhibition. Recombinant, chimeric Ig molecules delta/mu m and mu/delta m
      consisting of exons encoding extracellular delta and mu domains and membrane
      regions of different isotypes were constructed and introduced into WEHI-231
      cells. A similar approach was used for sIgG2b-expressing transfectants. Our
      findings indicate that the mu m region is not sufficient for regulation of growth
      inhibition in WEHI-231 cells and suggest that additional extracellular region(s)
      of mu chain may be required for this response.

PMID- 1396959
TI  - Modulation of restricted class II T cell responses by peptides derived from self
      class II molecule.
AB  - We have explored the possibility of using peptides derived from a major
      histocompatibility complex (MHC) class II (I-Ab) molecule to modulate I-Ab
      restricted T cell responses. Six peptides spanning the polymorphic regions of I
      Ab were analyzed for competitive binding to the I-Ab molecule, and for efficacies
      in blocking I-Ab-specific T cell response. Only PB1 (residues 75-91 of beta
      chain) bound the I-Ab molecule with high affinity. When these MHC-derived
      peptides were administered simultaneously with antigen, PB1 effectively inhibited
      I-Ab-restricted T cell responses as well as another peptide PB2 (residues 59-78
      of beta chain). PB2 inhibited specific T cell response only when it was
      administered simultaneously with antigen. Since PB2 is a weak binder of I-Ab, an
      additional mechanism must account for its inhibitory activity. Both PB1 and PB2
      peptides elicited specific T cell responses, indicating that these peptides were
      not tolerogenic in syngeneic mice. However, the induction of T cells in response
      to PB1 and PB2 did not increase reactivity to I-Ab. MHC class II-derived peptides
      thus can be used to regulate T cell responses without the risk of autoreactivity.

PMID- 1396960
TI  - Effects of the thymic microenvironment on the response of thymocytes to
      stimulation.
AB  - We show that, in vitro, the response of thymocytes to certain stimuli, and their
      survival largely depend on the nature of the culture environment, i.e. whether
      thymocytes are stimulated within intact thymus lobes or in cell suspension.
      Exposure of isolated thymocytes to 12-O-tetra-decanoylphorbol 13-acetate
      (TPA)+ionomycin rapidly abolishes the expression of recombination-activating gene
      1 (RAG-1) mRNA (3 h), down-regulates CD4 surface antigen expression (3 h), and
      enhances apoptosis (24 h). On the other hand, when thymocytes are cultured in
      intact lobes, TPA plus ionomycin down-regulate rather than abolish RAG-1 mRNA
      expression (3 h), have little effect on CD4 expression even following 24-h
      exposure, and only marginally induce apoptosis (24 h). Differences between the
      culture systems are less pronounced in response to anti-CD3 antibodies.
      Therefore, it appears that removing thymocytes from their thymic microenvironment
      makes the cells more susceptible to certain stimuli, possibly by altering their
      physiological status. In addition, it has been suggested that termination of RAG
      1 expression can be linked to thymocyte selection processes. We found that the
      down-regulation of RAG-1 expression was not dependent on the induction of
      apoptosis, supporting a proposed link with positive selection.

PMID- 1396961
TI  - Neurons and neuroblastoma as a source of macrophage colony-stimulating factor.
AB  - Accumulation of macrophages in brain tissue as observed in nervous system injury
      may be due to local production of hematopoietic colony-stimulating factors (CSF).
      The present work shows human neuroblastoma cells and murine neurons, namely
      granule cells of the cerebellum, to produce macrophage (M)-CSF which guides
      expansion and differentiation of macrophage lineage cells. The mRNA-encoding M
      CSF but not the respective protein is present in mouse brain including
      cerebellum. Neither granulocyte M-CSF nor IL-3 is produced by cerebellar neurons
      or neuroblastoma. By their production of M-CSF, neurons may regulate the
      macrophage response and lead to local expansion and enhanced function of
      macrophages in inflammatory diseases of the central nervous system.

PMID- 1396962
TI  - A trypsin-like serine protease activity on activated human B cells and various B
      cell lines.
AB  - We have studied the trypsin-like serine protease activity of human tonsillar B
      lymphocytes. The lysate of the low-density, in vivo activated B cells as well as
      the lysate of cells stimulated with anti-human IgM F(ab')2 show elevated trypsin
      like serine protease activity compared to the resting subset as monitored by the
      cleavage of Tos-Gly-Pro-Arg-pNA. The cleavage is sensitive to N-tosyl-L-lysyl
      chloromethyl ketone and benzamidine but not to iodoacetamide. Experiments with
      intact cells give similar results. The finding that the intact cells hydrolyze
      the substrate, while their supernatant does not, suggests that the protease
      activity is cell membrane associated. It is possible that C3 is a substrate of
      the enzyme since the activated B cells cleave C3, whereas the resting B cells do
      not, and also C3 inhibits the enzyme-substrate reaction. In addition to the ex
      vivo B cells, we studied the serine protease activity of certain well
      characterized B cell lines. The results show a correlation between the phenotype
      and the enzyme expression of the cell lines. BL41, an Epstein-Barr virus (EBV)
      negative Burkitt lymphoma line, with a resting phenotype, has low activity, while
      its EBV genome-carrying convertants E95-A-BL41, E95-C-BL41, EHR-A-BL41 and
      BL41/95 that have the phenotype of activated B cells, have high proteolytic
      activity. The lymphoblastoid cell line WW-1-LCL which has the phenotype of an
      immunoblast, has the highest serine protease activity. On the basis of the above
      data, we suggest that a rather tight correlation exists between the degree of
      activation and the appearance of serine protease(s) on the surface of human B
      cells.

PMID- 1396963
TI  - Genetics of nonspecific immunity: I. Bidirectional selective breeding of lines of
      mice endowed with maximal or minimal inflammatory responsiveness.
AB  - The genetic regulation of acute inflammatory reaction (AIR) was studied by the
      method of bidirectional selective breeding, used to produce a line of mice giving
      the maximal and a line of mice giving the minimal inflammatory reaction (AIR max
      and AIR min, respectively). The AIR was triggered by subcutaneous injection of a
      neutral substrate (suspension of polyacrylamide microbeads), and measured by the
      leukocyte and serum protein accumulation in the exudate. The two parameters are
      positively correlated and present a normal frequency distribution. The highly
      genetically heterogeneous foundation population was produced by the equipoised
      intercrossing of eight inbred strains of mice, and selective breeding carried out
      by assortative matings of extreme phenotypes. The response to selection in 11
      consecutive generations was highly asymmetrical: a marked AIR increase in the AIR
      max and no change in the AIR min line occurred. The mean value of realized
      heritability in the AIR max line was 0.26 and 0.18 for cell and protein
      concentrations, respectively. The response to selection must have resulted from
      the interaction of seven to nine independent gene loci endowed with additive
      effects. The lack of response to selection of the AIR min line is discussed. The
      large inter-line difference opens new possibilities for studying the biochemistry
      and molecular genetics of inflammation, and also for investigating the beneficial
      or detrimental effect of inflammatory responses.

PMID- 1396964
TI  - Tyrosine kinase activation in thymic epithelial cells: necessity of thymocyte
      contact through the gp23/45/90 adhesion complex.
AB  - Interactions between thymocytes and thymic stromal cells are necessary for T cell
      differentiation, maturation and proliferation. The signals required for these
      events to occur often necessitate close contact, and indeed adhesion, between the
      cell types involved. While the transmission of signals from stromal cells to
      thymocytes has been well documented, there is little evidence that binding of
      thymocytes to stromal cells can result in stromal cell activation. We have
      recently identified a novel thymic epithelial adhesion complex composed of three
      non-covalently associated glycoproteins (gp23, gp45 and gp90). While gp23 and
      gp45 are jointly required for adhesion to thymocytes, the function of gp90 is
      unknown. In the present work, we show that gp23/45-mediated contact with
      thymocytes induces de novo tyrosine phosphorylation of gp90. Furthermore, the
      protein tyrosine kinase responsible for gp90 neophosphorylation is itself an
      integral part of the adhesion complex.

PMID- 1396965
TI  - Evidence for oligoclonality of T cell receptor delta chain transcripts expressed
      in rheumatoid arthritis patients.
AB  - The inflamed synovium of rheumatoid arthritis (RA) patients contains gamma/delta
      T cells which express predominantly T cell receptor (TcR) variable (V) delta 1
      and V delta 2 chains. Such T cells may contribute to the pathogenesis of RA. To
      assess the extent of clonality among these T cell populations we sequenced the
      junctional regions of rearranged TcR V delta 1-C delta and V delta 2-C delta
      chain cDNA, after using the polymerase chain reaction (PCR) to amplify TcR delta
      chain transcripts isolated from synovial membrane mononuclear cells (SMC) of five
      RA patients. The sequences of these delta chain transcripts were compared with
      those found in peripheral blood mononuclear cells (PBMC) of the same patients and
      in PBMC of four healthy controls. In contrast to control PBMC, V delta 1 chain
      cDNA derived from PBMC of three patients showed a strong bias towards usage of
      the same V-joining (J) combination and junctional region sequences, although the
      specific sequences were unique in each patient. However, oligoclonality of the V
      delta 1 chain was less marked in SMC of two of these patients and absent in SMC
      of the other patients. For V delta 2, oligoclonality was detected in PBMC of two
      patients. In SMC of a single patient, a dominant V delta 2 transcript was
      detected that utilized the J delta 2 segment, which was rarely expressed in the
      normal TcR repertoire. These results indicate in vivo clonal expansion of V delta
      1- and V delta 2-expressing gamma/delta T cells in the peripheral blood of RA
      patients and a synovial T cell infiltrate which consists largely of polyclonally
      expanded gamma/delta T cells, but shows clonal dominance in some patients. Our
      data strongly support a role for V delta 1+ and V delta 2+ gamma/delta T cells in
      the pathogenesis of RA, and, although the nature of the antigen(s) recognized by
      these cells remains elusive, this report suggests the potential involvement of
      antigen(s) specific for the V region and V-J junction.

PMID- 1396966
TI  - Analysis of human/mouse interleukin-6 hybrid proteins: both amino and carboxy
      termini of human interleukin-6 are required for in vitro receptor binding.
AB  - The multifunctional cytokine interleukin-6 (IL-6) is a single polypeptide chain
      consisting of 184 amino acids in man and 187 amino acids in mouse. Despite the
      relatively high degree of sequence similarity of these two molecules (about 57%),
      the biological activity in mouse and human IL-6 shows species specificity.
      Starting with this observation, we constructed interspecies hybrids with the goal
      of defining which segments of the human IL-6 molecule are involved in human
      receptor binding. In this manner we generated multiple amino acid substitution
      mutants which do not contain insertions or deletions as compared with the
      parental proteins, and which, therefore, should not show dramatic changes in
      folding. Using two biological assays on cells of human and mouse origin and a
      recently developed in vitro binding assay to recombinant soluble human IL-6
      receptor, we obtained results which indicate that both the amino and carboxy
      termini are necessary and sufficient for efficient binding, but that the carboxy
      terminus plays the dominant role in receptor recognition.

PMID- 1396967
TI  - Lipopolysaccharide induces human interleukin-1 receptor antagonist and
      interleukin-1 production in the same cell.
AB  - A new member of the interleukin-1 (IL-1) family has recently been described.
      Human IL-1 receptor antagonist (IL-1ra) is structurally related to IL-1 alpha and
      IL-1 beta but binds to IL-1 receptors on various target cells without
      demonstrable agonist activity. Understanding the mechanisms of regulation of IL
      1ra production may clarify the biology of this unique cytokine as well as
      elucidate its possible role as a natural anti-inflammatory protein. The effects
      of lipopolysaccharide (LPS) on IL-1 alpha, IL-1 beta and IL-1ra production was
      studied at a single-cell level by use of cytokine-specific antibodies and
      indirect immunofluorescence technique. The peak synthesis of IL-1ra and IL-1
      alpha/beta occurred in peripheral blood monocytes obtained from healthy blood
      donors within 4 and 6 h of cell stimulation, respectively. By double-staining
      procedure all IL-1ra-positive cells were also IL-1 alpha and/or beta positive.
      Thus, endotoxin induced simultaneous synthesis of the IL-1 gene family in the
      same cells. Only monocytes contributed to the production of IL-1 alpha, beta and
      IL-1ra during the 96 h of cell culture. The maximum number of IL-1ra-producing
      monocytes was 48 +/- 16% as compared to peak production of IL-1 alpha and beta
      which occurred in 75 +/- 9% and 80 +/- 12% (p < 0.001), respectively, of all
      peripheral blood monocytes. The incidence of IL-1 alpha- and beta-containing
      cells was not only significantly higher but also occurred for a longer time
      period, 72 h as compared to 24 h for IL-1ra localized in the Golgi organelle.
      However, IL-1ra-containing cells with a diffuse cytoplasmic appearance were also
      evident (20%-30%) at a later stage, 12 to 72 h after stimulation. Blocking IL-1
      surface receptors by addition of exogenous recombinant IL-1 beta before
      stimulation could not inhibit the diffuse cytosolic localization. This indicates
      that the "late" staining pattern did not reflect IL-1ra being secreted and
      internalized after binding to extracellular receptors. Thus, perhaps IL-1ra
      modulates IL-1 effector mechanisms by receptor interactions both inside and
      outside the cell.

PMID- 1396968
TI  - T cell repertoire in tuberculosis: selective anergy to an immunodominant epitope
      of the 38-kDa antigen in patients with active disease.
AB  - It is generally accepted that both host protection and pathogenic reactions in
      tuberculosis are mediated by T lymphocytes. However, little is known about the
      structures and discreet functions of epitopes stimulating the immune response. In
      this study, proliferative responses of blood T lymphocytes to synthetic peptides
      derived from the sequence of the 38-kDa antigen from Mycobacterium tuberculosis
      have been investigated in 41 healthy individuals and in 36 patients with active
      tuberculosis. Of the healthy purified protein derivative (PPD)-positive donors,
      90% responded to a permissively recognized peptide, 38.G (residues 350-359),
      located at the carboxy terminus of the molecule. Four other permissively
      recognized epitopes of this molecule (38.A, 38.I, 38.E, 38.K) were stimulatory
      for more than 50% of healthy PPD-positive individuals. Patients with lymphatic
      tuberculosis responded to these peptides in a similar manner. In contrast, we
      observed a selective anergy to stimulation with peptide 38.G in the majority of
      patients with pulmonary (11% responders) and nonlymphatic extrapulmonary
      tuberculosis (25% responders). The lack of responsiveness to 38.G was epitope
      specific since the degree of responsiveness to the other four permissively
      recognized peptide epitopes was similar for patients and PPD-positive controls.
      Using the PEPSCAN technology and truncated peptides, the core epitope of 38.G was
      localized to a peptide 10 amino acids long (HFQPLPPAVV). This minimal structure
      was capable of inducing a proliferative response in all healthy 38.G responders
      tested. The mechanisms influencing this epitope-specific anergy in patients could
      give new insights into the immunopathogenesis of tuberculosis.

PMID- 1396969
TI  - Pore-forming protein in individual cytotoxic T lymphocytes: the effect of
      senescence provides a probe for understanding the lytic mechanism.
AB  - The senescent decline of cytolytic T lymphocyte (CTL) activity was examined (a)
      to learn more about the effect of aging on the immune system, and (b) to probe
      the mechanism of cell-mediated cytolysis. The effect of age on the generation of
      pore-forming protein (Pfp) was examined at the cellular level in a murine model
      using CTL stimulated in allogeneic mixed lymphocyte culture (MLC). Pfp expression
      was analyzed by immunocytochemistry and enzyme-linked immunosorbent assay
      (ELISA). Immunocytochemical analyses of Pfp in MLC-stimulated splenic T cells
      from a large number of mice revealed that although stimulated cells from aged
      mice exhibited fewer Pfp-producing cells than those from young, the diminution in
      the proportion of Pfp+ cells was small compared to the age-related decrease in
      lytic activities (approximately 2-fold vs. approximately 7.4-fold, respectively).
      Time-course analysis disclosed similar kinetics for the generation of Pfp+ cells
      among responding cells from young and aged mice. No significant age-related
      difference in the proportion of Pfp+ cells was observed in MLC-stimulated lymph
      node cells despite a large and significant difference in lytic activity
      (approximately 6.5-fold). Purified CD8+ T cells demonstrated a large age-related
      difference in CTL activity (approximately 3-11-fold) and accounted for virtually
      all the Pfp. Although little difference in the proportion of Pfp+ CD8+ T cells
      could be detected between age groups, stimulated CD8+ cells or whole splenic T
      cells from old mice consistently exhibited a striking reduction in both the
      intensity of Pfp staining and the apparent numbers of granules per cell. This
      difference in Pfp was examined by ELISA and total Pfp levels were found to be
      approximately 12-fold greater in CTL generated from splenic T cells of young
      compared to aged mice. The results demonstrate that Pfp levels are reduced in CTL
      from aged compared to young mice at the level of the individual cells and suggest
      the possibility that a threshold level of Pfp may be required for potency of
      effector cell function.

PMID- 1396970
TI  - Expression of major histocompatibility complex class I antigens at low levels in
      the thymus induces T cell tolerance via a non-deletional mechanism.
AB  - Transgenic CBA (H-2k haplotype) mice expressing the H-2 Kb major
      histocompatibility complex (MHC) class I gene under control of transcriptional
      promoter elements from a milk protein gene display high-level H-2 Kb
      transcription in lactating mammary glands and low-level transcription in skin and
      thymus of male and virgin female transgenic mice. However, H-2 Kb antigen could
      be detected only in lactating mammary gland epithelial cells by
      immunohistological methods. All transgenic mice are tolerant of H-2 Kb since they
      fail to reject skin grafts from mice expressing H-2 Kb molecules. Furthermore,
      anti-H-2 Kb cytotoxic responses could not be generated using responder T cells
      from transgenic mice but T cells from the same mice proliferated, in the presence
      of interleukin-2, in response to stimulator cells expressing H-2 Kb. Tolerance to
      H-2 Kb is induced in the thymus since CBA mice grafted with thymus tissue from
      transgenic mice fail to reject H-2 Kb disparate skin grafts. However, experiments
      with double-transgenic mice also expressing a T cell receptor with anti-H-2 Kb
      specificity reveal that tolerance induction is not brought about by elimination
      of thymocytes bearing H-2 Kb-reactive receptors. Instead, a non-deletional
      mechanism which results in down-modulation of both CD8 and T cell receptor
      expression in peripheral T cells correlates with the induction of tolerance in
      these mice. These data reveal that extremely low levels of self-antigen
      expression in the thymus are sufficient to induce tolerance via non-deletional
      mechanisms.

PMID- 1396971
TI  - Dissection of major histocompatibility complex (MHC) and T cell receptor contact
      residues in a Kb-restricted ovalbumin peptide and an assessment of the predictive
      power of MHC-binding motifs.
AB  - The effect of alanine substitution on the major histocompatibility complex (MHC)
      binding and T cell receptor recognition of the Kb-restricted ovalbumin 257-264
      peptide was investigated. Positions 3, 5 and 8 of the octamer were important for
      Kb binding, as predicted from the motifs found in Kb-associated peptides, while
      mutations at positions 4, 6 and 7 affected cytotoxic T lymphocyte recognition.
      Substitutions at positions 1 and 2 had very minor effects on T cell recognition.
      In addition, we tested the capacity of sequence motifs to predict MHC binding by
      analysis of a series of peptides which all bear the minimal Kb motif. We found
      that possession of good motifs was not always sufficient to give strong MHC
      binding, indicating secondary effects of the residues flanking the "MHC anchor"
      positions.

PMID- 1396972
TI  - The CD39 molecule defines distinct cytotoxic subsets within alloactivated human
      CD8-positive cells.
AB  - Lymphocyte activation induces or increases the expression of several surface
      structures, none of which is characteristic of an activated cell subset. In
      particular, structures such as CD45RO, CD25, CD26, CD49b, CD54, CD71 are
      expressed by the vast majority of lymphocytes at various times following in vitro
      activation. CD39 molecules were originally identified on activated B lymphocytes
      and have recently been described on activated T cell clones. In the present
      report, we have characterized phenotypically and functionally defined cell
      subsets generated during an in vitro allostimulation. Results indicated that the
      percentage of CD39+ cells reached a maximum at day 6 and remained stable
      thereafter. We demonstrate that CD39 expression allows the identification within
      the allosensitized CD8+ cytotoxic cells of distinct subsets of cells mediating
      allo cytotoxic T lymphocyte or natural killer (NK)-like reactivity. More
      precisely, CD8+CD39+ alloactivated cells mainly mediate specific killer activity,
      whereas CD8+CD39- alloactivated cells predominantly exhibit NK-like reactivity.
      Further, we show a high functional correlation associated with the lack of CD39
      expression on NK-like alloactivated CD8+ cells, while there is no association
      with CD56 or CD57 NK-associated structures.

PMID- 1396973
TI  - Alpha 1-acid glycoprotein potentiates lipopolysaccharide-induced secretion of
      interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha by human
      monocytes and alveolar and peritoneal macrophages.
AB  - Although the physiological role of alpha 1-acid glycoprotein (AGP), an acute
      phase protein, is poorly understood, several lines of evidence support a
      modulatory action on the immune response. In this study, we investigated the
      effect of AGP on the production of interleukin (IL)-1 beta, IL-6 and tumor
      necrosis factor (TNF)-alpha by human monocytes, macrophages and the monocytic THP
      1 cell line. AGP significantly enhanced (2- to 7-fold) the production of these
      cytokines in monocytes induced by suboptimal concentrations of lipopolysaccharide
      [E. coli lipopolysaccharide (LPS): 100 ng/ml] in serum-free conditions, whereas
      it had little or no effect in the absence of LPS. The potentiating effect of AGP
      was inhibited by specific antibodies. It was concentration dependent and the
      greatest enhancement was observed with 250-500 micrograms/ml. Moreover, AGP only
      potentiated the effect of suboptimal concentrations of LPS. AGP did not alter the
      time course of LPS-induced IL-1 beta, IL-6 or TNF-alpha secretion. AGP acts as a
      co-inducer and could also potentiate cytokine secretion triggered by Neisseria
      meningitidis LPS and muramyl dipeptide. The glycan moiety of AGP did not seem to
      be involved in its potentiating effect, since both its major glycoforms and
      asialo-AGP potentiated the effect of LPS to the same extent as native AGP.
      Possible differences in the effect of AGP according to cell maturation were
      investigated using isolated human macrophages: AGP potentiated LPS-induced
      cytokine production by both peritoneal and alveolar macrophages. These data
      suggest that AGP can modulate monocyte/macrophage functions, thereby contributing
      to the amplification and regulation of immune and inflammatory responses.

PMID- 1396974
TI  - Self tolerance to human A and B histo-blood group antigens exists at the B cell
      level and cannot be broken by potent polyclonal B cell activation in vitro.
AB  - It is generally considered that tolerance to self antigens is less complete in B
      than in T lymphocytes. However, B cell tolerance through either functional
      inactivation (anergy) or clonal deletion has been demonstrated in transgenic
      mice. In the present study, we investigated whether B cells specific for self A/B
      histo-blood group antigens can be detected in normal humans. It is a key feature
      of the ABO system that all normal individuals make natural antibodies against
      those A or B carbohydrates which are not present in their organism. To detect B
      cells by the limiting dilution approach we used a specific enzyme-linked
      immunosorbent assay for the quantitation of anti-A/B antibodies, and a culture
      system in which polyclonal B cell activation occurs through cell contact with EL4
      thymoma cells. As was reported for other B cell studies, we frequently detected
      "polyreactive" immunoglobulin (Ig)M (but not IgG) with apparent autoreactivity
      but of uncertain significance regarding physiologic conditions. However, A- or B
      specific B cell responses occurred with selective patterns in agreement with
      classical blood group serology in 14 individuals with A, B, AB or 0 blood group
      phenotypes: 1/11,600 B cells made anti-allo A/B IgM and 1/26,500 B cells such as
      IgG, while only 1/104,000 B cells apparently made anti-self A/B IgM and 1/350,000
      B cells such as IgG. This shows self tolerance at the B cell level. Since anergy
      of B cells can frequently be broken by polyclonal B cell activation in vitro, and
      EL4 cells are potent B cell stimulators, the present results argue for either a
      highly resistant anergic state or for clonal deletion of self-A/B histo-blood
      group-specific human B cells.

PMID- 1396975
TI  - Effects of HIV-1 Tat protein on human T cell proliferation.
AB  - In inducing immunodeficiency in human immunodeficiency virus (HIV)-1 infection, a
      role for the HIV-1 Tat protein has been suggested. In addition to effects on
      viral transcription, the protein has been ascribed immunosuppressive functions,
      which were investigated in this study. Proliferation of purified T cells to CD3
      monoclonal antibodies immobilized to plastic plates was inhibited up to 70% by
      addition of 5 micrograms/ml of the Tat protein. This inhibitory effect, however,
      was not observed in the presence of accessory cells. Furthermore, no effect of
      Tat protein could be observed on T cell proliferative responses to recall antigen
      which most likely is related to the presence of accessory cells in the cultures.
      Taken together, our results do not imply an important role for immunosuppressive
      effects of Tat in induction of immunodeficiency as observed in HIV infection in
      vivo.

PMID- 1396976
TI  - c-myc-induced natural killer cell sensitivity of human melanoma cells is reversed
      by HLA-B27 transfection.
AB  - In human melanoma, activation of the c-myc oncogene results in locus-specific
      down-modulation of the HLA-B antigen expression. Moreover, overexpression of c
      myc induces an increase of natural killer (NK) sensitivity of the tumor cells. To
      show that this effect on susceptibility to NK cells is mediated by the down
      modulation of the HLA-B expression rather than by the activation of the oncogene,
      we supertransfected a c-myc transfectant with the gene encoding the HLA-B27
      protein. The resulting supertransfectants with HLA-B27 surface expression were
      all less sensitive to NK cells than their parental cell line and showed a level
      of resistance equal to the original melanoma cell line with low c-myc expression.
      This indicates that the induction of NK sensitivity by c-myc activation in human
      melanoma cells is mediated through down-modulation of the HLA-B expression. These
      data also imply differential effects of HLA-A and HLA-B molecules on lysis by NK
      cells, because the level of NK susceptibility can apparently be defined by the
      level of HLA-B, irrespective of a substantial level of HLA-A expression present
      in the tumor cells.

PMID- 1396977
TI  - Nitric oxide mediates suppression of T cell responses in murine Trypanosoma
      brucei infection.
AB  - African trypanosomes induce a generalized state of immunosuppression in their
      mammalian hosts. One characteristic of this is a suppression of lymphocyte
      responses to mitogen, which is mediated by suppressor macrophages. We
      investigated the involvement of nitric oxide in this phenomenon. Both peritoneal
      and splenic cell cultures from infected mice released nitrite and this was
      inhibitable by NG-monomethyl L-arginine (L-NMMA). The release of nitrite
      correlated with suppressed splenic T cell proliferative responses to concanavalin
      A. It was shown that adherent spleen cells from infected mice mediate
      suppression, which could be abrogated by L-NMMA. These results suggest that in T.
      brucei infection, the activation of macrophages to produce nitric oxide leads to
      impaired lymphocyte responses and immunosuppression.

PMID- 1396978
TI  - A versatile method to produce antibodies to human T cell receptor V beta
      segments: frequency determination of human V beta 2+ T cells that react with
      toxic-shock syndrome toxin-1.
AB  - Human V beta (hV beta) regions have been expressed in the context of mouse T cell
      receptor (TcR)-CD3 complexes, and subsequently used to raise hV beta-specific
      monoclonal antibodies (mAb). The method of expression of hV beta outlined in this
      report contrasts in its versatility with the one reported by Choi et al. (Proc.
      Natl. Acad. Sci. USA 1991. 88: 8357). For instance, we have applied it
      successfully to the construction of mouse T cell transfectants expressing hV beta
      1, hV beta 2, hV beta 3, hV beta 8, hV beta 9, hV beta 13.5, hV beta 19, hV beta
      21, and hV beta 22 gene segments. mAb against the hV beta 2 and hV beta 19
      regions have been raised by using these transfectants as immunogens in mice.
      Here, we illustrate the application of the anti-hV beta 2 mAb to the measurement
      of human T cells that react with the staphylococcal toxic-shock syndrome toxin-1.

PMID- 1396979
TI  - The B29 and mb-1 polypeptides are differentially expressed during human B cell
      differentiation.
AB  - Surface immunoglobulin on mouse B cells is associated with a heterodimer
      comprising the products of the mb-1 and B29 genes. Here we report that antibodies
      raised against a peptide sequence from the intracytoplasmic C terminus of the B29
      murine gene product detect the 37-kDa component of the human heterodimer,
      indicating that this component in man is also encoded by the B29 gene. The
      immunocytochemical reactivity of these anti-B29 antibodies was compared with
      those of antibodies to the mb-1 protein. Of 25 cases of acute lymphoblastic
      leukaemia (ALL), 24 were positive for mb-1 whereas B29 was expressed in only 13
      cases. Most of these B29-positive ALL expressed immunoglobulin mu heavy chain in
      their cytoplasm (pre-B ALL). In lymphoid tissue sections, anti-B29-labeled B cell
      follicles in a similar fashion to anti-mb-1, with the striking exception that
      plasma cells were unreactive for B29, but positive for mb-1. These results
      suggest that the synthesis of B29 begins later in precursor B cells than that of
      mb-1, and ceases before the terminal plasmacyte phase.

PMID- 1396980
TI  - Quantitative analysis of the response of human T cell receptor V gamma 9+ cells
      to Plasmodium falciparum.
AB  - Plasmodium falciparum stimulates peripheral blood gamma delta + T cells from
      unexposed donors. The responding cells bear V gamma 9+ chains of the T cell
      receptor, the majority of which, but not all, are associated with V delta 2
      chains. We have analyzed whether the precursor frequency of these V gamma 9+
      cells approaches that expected of superantigens or mitogens and whether, like a
      superantigen, the response is major histocompatibility complex (MHC)
      unrestricted. Limiting dilution analyses of the response of enriched gamma delta
      + T cells to P.falciparum using autologous and heterologous antigen-presenting
      cells suggest that the response is more characteristic of an antigen-specific MHC
      restricted response. The frequencies are lower than would be expected if all V
      gamma 9+ cells respond, and there is a dramatically reduced response when
      allogeneic antigen-presenting cells are used.

PMID- 1396981
TI  - High frequency of somatically mutated IgM molecules in the human adult blood B
      cell repertoire.
AB  - Nucleotide sequence analysis of cDNA encoded by the single member of the human
      immunoglobulin VH6 gene family show that blood B cells in adults, but not in
      neonates, frequently express somatically mutated IgM molecules. The number of
      mutations in VH6-encoded cDNA from adult blood ranged from 2 to 19 mutations/VH
      gene (average 10.1/VH gene). The distribution of silent and replacement mutations
      suggests that at least some of the VH6 genes were derived from B cells that were
      activated and selected by antigen. We conclude that the blood B cell repertoire
      in adult humans, in contrast to its much-studied murine splenic counterpart, is a
      rich source of highly mutated IgM molecules.

PMID- 1396982
TI  - Electropharmacology of dofetilide, a new class III agent, in anaesthetised dogs.
AB  - In open chest anaesthetised dogs, dofetilide increased the ventricular effective
      refractory period over the dose range 1-100 micrograms/kg i.v. and the
      ventricular fibrillation threshold at doses between 3-100 micrograms/kg and was
      80-1000 times more potent than sematilide, racemic sotalol, d-sotalol or
      quinidine. The maximal increases in ventricular fibrillation threshold induced by
      sematilide and quinidine were less than that induced by the other drugs. A change
      in the character of the induced arrhythmia from true ventricular fibrillation to
      a rapid ventricular flutter, with frequent spontaneous conversion, was observed
      following all drugs. No adverse haemodynamic effects of dofetilide, sematilide or
      d-sotalol were observed, but quinidine induced marked cardiac depression and
      racemic sotalol also impaired left ventricular contractility. All drugs reduced
      heart rate, though the effect of racemic sotalol was clearly greater than that of
      the other agents. Dofetilide is a potent class III antiarrhythmic agent with
      antifibrillatory properties and a favourable haemodynamic profile.

PMID- 1396983
TI  - Effects of drugs on behavior before and during chronic diazepam administration.
AB  - The effects of diazepam, pentobarbital, and phencyclidine (PCP) were studied on
      punished and unpunished responding maintained by fixed-interval schedules before
      and during chronic administration of diazepam. Before chronic diazepam
      administration, increasing doses of diazepam and PCP increased and then decreased
      rates of both punished and unpunished responding. Increases in punished
      responding were larger than increases in unpunished responding. Pentobarbital
      only increased punished responding, while higher doses decreased both rates of
      punished and unpunished responding. During chronic diazepam administration, rates
      of punished and unpunished responding showed further increases with all three
      drugs and the dose-effect curves also shifted to the right. Analysis of local
      rates of responding within fixed-interval components suggested that increases in
      low rates early in the interval were responsible for the rate increases produced
      by these drugs before chronic diazepam administration. During chronic diazepam
      administration low rates early in the interval showed greater increases after all
      three drugs and their ability to produce rate-increasing effects extended further
      into the interval. The similar effects of these drugs before and during chronic
      diazepam administration suggests a similar mechanism despite the widely
      recognized differences in their interaction with receptors. This common mechanism
      may relate to rate-increasing effects more than to specific effects on punished
      responding.

PMID- 1396984
TI  - Chronic estrogen alters contractile responsiveness to angiotensin II and
      norepinephrine in female rat aorta.
AB  - Sex hormones have been postulated to play an important role in the modulation of
      vascular responsiveness to endogenous vasoactive substances. This study was
      designed to establish the effects of chronic treatment with estrogen in vivo on
      subsequent contractile responsiveness of aortic rings to angiotensin II or
      norepinephrine in vitro. Concentration-response curves for angiotensin II were
      compared in aortic rings with or without endothelium isolated from ovariectomized
      rats (275-299 g) pretreated with 17 beta-estradiol (approximately 1 mg/kg per
      day) or placebo for 14 days and from normal prepubertal female rats (125-149 g)
      pretreated with 17 beta-estradiol (approximately 5 mg/kg per day) or placebo for
      14 days. Whether or not endothelium was present, angiotensin II-induced
      contraction was significantly depressed in rings from 17 beta-estradiol-treated
      ovariectomized or prepubertal rats when compared to controls, and the pattern of
      the effects of 17 beta-estradiol-treatment on the concentration-response curves
      for angiotensin II was similar in the two models. In contrast to angiotensin II
      induced contraction, norepinephrine-induced contraction was significantly
      enhanced in aortic rings with or without endothelium from ovariectomized rats
      pretreated with 17 beta-estradiol (approximately 1 mg/kg per day, 14 days) and
      from normal prepubertal female rats pretreated with 17 beta-estradiol
      (approximately 5 mg/kg per day, 14 days) when compared to controls. The results
      demonstrate that chronic treatment with 17 beta-estradiol selectively reduced and
      enhanced contractile responsiveness of aortic rings to angiotensin II and
      norepinephrine, respectively. Further, the results indicate that the normal
      prepubertal female rat is an efficient model to investigate modulation by
      estrogen of aortic responsiveness to vasoactive agents in vitro.

PMID- 1396985
TI  - Effects of K+ channel blockers on the relaxant action of dihydralazine,
      cromakalim and nitroprusside in isolated rabbit femoral arteries.
AB  - The relaxant responses to dihydralazine and the influence of different K+ channel
      blockers were studied in isolated rabbit femoral arteries. The prototype K+
      channel opener, cromakalim, and nitroprusside, which does not produce relaxation
      by K+ channel activation were used for comparison. Dihydralazine was most
      effective on contractions induced by noradrenaline (EC50 = 1.1 microM; Emax =
      95%) and relaxed the contractions elicited by 20 mM K+ (EC50 = 2.0 microM; Emax =
      81% in preference to 124 mM K(+)-induced contractions (EC50 = 30.1 microM; Emax =
      54%). Cromakalim, but not nitroprusside, also selectively relaxed 20 mM K(+)
      induced contractions. In noradrenaline-contracted arteries, glibenclamide (10
      microM) completely suppressed the relaxant response to cromakalim but did not
      influence the vasorelaxation produced by dihydralazine or nitroprusside.
      Tetraethylammonium (8 mM) and Cs+ (4 mM) shifted the concentration-relaxation
      curve for dihydralazine 2-fold to the right, whereas Ba2+ (0.1 mM), 4
      aminopyridine (5 mM) and procaine (0.1 mM) failed to influence dihydralazine
      induced responses. Tetraethylammonium (8 mM) shifted the concentration-relaxation
      curve for cromakalim and nitroprusside 6-fold to the right and suppressed the
      maximal relaxant effects by about 30%. It is concluded that dihydralazine
      produces vascular smooth muscle relaxation by a mechanism different from the
      opening of glibenclamide- and ATP-sensitive K+ channels.

PMID- 1396986
TI  - Inhibition of [3H]paroxetine binding by various serotonin uptake inhibitors:
      structure-activity relationships.
AB  - Fifty-four compounds structurally related to zimeldine or alaproclate and eight
      reference substances were examined as inhibitors of the high affinity binding of
      [3H]paroxetine to rat cerebral cortical membranes as a measure of the affinity of
      the 5-hydroxytryptamine (5-HT) transporter. None of the compounds had an affinity
      as high as paroxetine (KD = 0.026 nM). The most potent compound, 3-(4
      methoxyphenyl)-1-methyl-3-phenylpropylamine (2) had a 5 times lower affinity than
      paroxetine. Some other diphenyl-1-methyl-propylamines displayed high affinity,
      e.g. the 4-bromo (4) and 2-bromo (7) derivatives. The primary amine analogue of
      zimeldine substituted with an alpha-methyl group (19) had an affinity only
      slightly less than that of norzimeldine (11) but an almost 100 times higher
      affinity than that of the unsubstituted primary zimeldine analogue (57). These
      observations indicate that a methyl group on the alpha-carbon and on the nitrogen
      both increase the affinity for the [3H]paroxetine binding site. The structure
      activity relationship for the compounds to inhibit [3H]paroxetine binding was
      highly significantly correlated to the inhibition of 5-HT uptake in mouse brain
      slices (P less than 0.01) and to the inhibition of noradrenaline uptake in the
      same slices (P less than 0.05). QSAR analysis of the zimeldine series of
      compounds indicates that substitution of halogens of the 2-position of the phenyl
      ring is unfavourable. The cis configuration promotes higher activity than the
      trans configuration.

PMID- 1396987
TI  - Anticonvulsant activity of competitive antagonists of NMDA receptor in
      genetically epilepsy-prone rats.
AB  - The potency of some competitive antagonists of N-methyl-D-aspartate (NMDA) to
      antagonize audiogenic seizures was evaluated in genetically epilepsy-prone rats
      following intraperitoneal or oral administration. The anticonvulsant effects were
      evaluated on seizures evoked by auditory stimulation (109 dB, 12-16 kHz) in
      animals placed singly under a perspex dome. Sixty and hundred-twenty minutes
      after intraperitoneal or 120 min after oral administration all compounds showed
      antiseizure activity with ED50 against clonus ranging from 11.6 to 384 mumol/kg
      after intraperitoneal and higher doses after oral administration. DL-(E)-2-Amino
      4-methyl-5-phosphono-3-pentenoic acid (CGP 37849) and its carboxyethylester (CGP
      39551) and 3-((+/-)-2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid
      (CPPene), were the most potent compounds when administered intraperitoneally and
      orally. 3-((+/-)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid ((-)-CPP) and
      (+)-CPP showed minor potency as anticonvulsants and 2-amino-7-phosphonoheptanoic
      acid (2AP7) was the least potent. Following oral treatment, the duration of
      action of CPPene was about 8 h, while CGP 39551 still protected against
      audiogenic seizures after 16 h. All compounds were anticonvulsant at doses below
      those at which overt behavioural side-effects were apparent. CPPene and (+/-)-CPP
      showed the best therapeutic index among the NMDA receptor antagonists studied.
      Since some of these compounds showed anticonvulsant properties after oral
      administration, potential use of these or other selective NMDA antagonists for
      antiepileptic therapy in man is suggested.

PMID- 1396988
TI  - Effects of imidazoline-related compounds on the mechanical response to nicorandil
      in the rat portal vein.
AB  - The purpose of this study was to investigate the interactions of compounds
      structurally related to imidazoline at K+ channels located in the rat portal
      vein. Nicorandil, a K+ channel activator, dose dependently inhibited spontaneous
      contractions of the isolated rat portal vein. Glibenclamide (0.1-1 microM), an
      ATP-sensitive K+ channel blocker, competitively antagonized the response to
      nicorandil, whereas methylene blue (10 microM), a guanylate cyclase inhibitor,
      did not. Phentolamine, antazoline, tolazoline, and midaglizole also shifted the
      dose-response curve for nicorandil to the right in the dose range of 1-100
      microM. The rank order of potency was glibenclamide much greater than
      phentolamine = antazoline = midaglizole greater than tolazoline. In contrast,
      clonidine, idazoxan, imidazole, 1-benzylimidazole, and yohimbine were
      ineffective. In addition, cromakalim (1-100 nM), a selective K+ channel
      activator, also inhibited spontaneous contractions of the rat portal vein, and
      this effect was antagonized by phentolamine in a similar way to that found with
      nicorandil. These results suggest that some 2-substituted imidazolines, including
      phentolamine, possibly act as K+ channel blockers, like glibenclamide, in
      vascular smooth muscle.

PMID- 1396989
TI  - Possible implication of peptidase activity in different potency of angiotensins
      II and III for displacing [125I]angiotensin II binding in pig aorta.
AB  - A single class of [125I]angiotensin II ([125I]AII) binding sites was found in
      porcine aortic smooth muscle membranes. Des-Asp1-AII (AIII) and des-Asp1
      [Ile8]AII were 20 times less potent than AII or [Sar1,Ile8]AII to displace
      [125I]AII binding. In contrast, AII and AIII equipotently induced an increase in
      cytosolic free Ca2+ concentration in cultured porcine aortic smooth muscle cells.
      Des-Asp1-[Ile8]AII and [Sar1,Ile8]AII equipotently inhibited the increase induced
      by either AII or AIII. In order to explain this discrepancy, we studied
      [125I]AIII binding. In the presence of amastatin or a potent inhibitor of
      aminopeptidase M, [125I]AII binding remained stable for 90 min, but [125I]AIII
      binding decreased gradually after the peak at 30 min. The decrease was completely
      blocked by the presence of amastatin and phenylmethylsulfonylfluoride.
      Consequently, AIII was as potent as AII to displace [125I]AII binding in the
      presence of these two protease inhibitors. These results suggest that the lower
      potency of AIII to displace [125I]AII binding is related primarily to AIII
      specific degradation by proteases.

PMID- 1396990
TI  - Extract of kava (Piper methysticum) and its methysticin constituents protect
      brain tissue against ischemic damage in rodents.
AB  - The purpose of the present study was to test whether kava extract and its
      constituents kawain, dihydrokawain, methysticin, dihydromethysticin and yangonin
      provide protection against ischemic brain damage. To this end, we used a model of
      focal cerebral ischemia in mice and rats. Ischemia was induced by microbipolar
      coagulation of the left middle cerebral artery (MCA). To quantify the size of the
      lesion in mice, the area of the infarct on the brain surface was assessed
      planimetrically 48 h after MCA occlusion by transcardial perfusion of carbon
      black. In the rat model infarct volume was determined 48 h after MCA occlusion by
      planimetric analysis and subsequent integration of the infarct areas on serial
      coronal slices. Compounds were administered i.p., except the kava extract, which
      was administered orally. The effects of the kava extract and its constituents
      were compared with those produced by the typical anticonvulsant, memantine. The
      kava extract, methysticin and dihydromethysticin produced effects similar to
      those of the reference substance memantine. The kava extract (150 mg/kg, 1 h
      before ischemia) diminished the infarct area (P less than 0.05) in mouse brains
      and the infarct volume (P less than 0.05) in rat brains. Methysticin,
      dihydromethysticin (both 10 and 30 mg/kg, 15 min before ischemia) and memantine
      (20 mg/kg, 30 min before ischemia) significantly reduced the infarct area in
      mouse brains. All other compounds failed to produce a beneficial effect on the
      infarct area in mouse brains. In conclusion, the kava extract exhibited
      neuroprotective activity, which was probably mediated by its constituents
      methysticin and dihydromethysticin.

PMID- 1396991
TI  - The effect of intravenous recombinant human renin on blood pressure in pithed
      spontaneously hypertensive rats.
AB  - The effect of highly purified recombinant human renin (rh-renin), expressed in
      Chinese hamster ovary cells, on mean blood pressure (MBP) was evaluated in pithed
      spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous
      bolus injection of rh-renin produced dose-dependent increases in MBP in pithed
      SHR and WKY. The pressor response to rh-renin in pithed SHR was about 3 times as
      potent as that in pithed WKY. Intravenous infusion of rh-renin produced dose
      dependent progressive increases in MBP during the first 40 min, reaching plateaus
      and thereafter MBP was maintained up to 120 min. This hypertensive response to rh
      renin was antagonized by renin inhibitors, YM-21095 and KRI-1314, which inhibited
      the reaction between rh-renin and tetradecapeptide competitively, with Ki values
      of 5.1 x 10(-10) and 4.3 x 10(-9) M, respectively. In rh-renin-infused pithed
      SHR, the hypotensive effect of YM-21095 was 37 times as potent as that of KRI
      1314. These results suggest that rh-renin can stimulate the rat renin-angiotensin
      system, thereby producing hypertension. Moreover, the rh-renin-infused rat model
      could be useful to evaluate the effect of renin inhibitor.

PMID- 1396993
TI  - Effect of aldose reductase inhibitor on the inhibition of platelet aggregation
      induced by diabetic rat plasma.
AB  - Plasma isolated from streptozotocin-induced diabetic rats inhibited platelet
      aggregation. Treatment of diabetic rats with an aldose reductase inhibitor, ONO
      2235, which did not improve hyperglycemia, prevented the antiaggregating activity
      of plasma as did insulin treatment. Both treatments reduced the elevated sorbitol
      concentrations in erythrocytes. Although the factor(s) accounting for the
      antiaggregatory effect of diabetic plasma has not yet been characterized, it is
      possible that the accumulation of sorbitol in erythrocytes is related to the
      generation of the factor(s).

PMID- 1396992
TI  - Inhibition of uptake of 1-methyl-4-phenylpyridinium ion and dopamine in striatal
      synaptosomes by tobacco smoke components.
AB  - To determine whether the attenuation of 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced neurotoxicity by tobacco smoke exposure is
      caused by inhibition of the neuronal uptake of 4-phenylpyridinium ion (MPP+),
      various tobacco components and a smoke extract were tested for inhibitory
      activity in striatal synaptosomes. A dimethylsulfoxide extract of tobacco smoke
      filtrate was found to inhibit the uptake of MPP+ and dopamine. These results
      suggest that inhibition of the neuronal dopamine uptake mechanism may account for
      the protective effects of smoke exposure on MPTP-induced neurotoxicity.

PMID- 1396994
TI  - Chronic morphine treatment causes down-regulation of spinal adenosine A1
      receptors in rats.
AB  - Recent studies suggest that the release of adenosine in the spinal cord may be a
      significant component of the morphine antinociceptive action. We wanted to know
      whether the spinal adenosine system is involved in morphine tolerance. Animals
      were rendered tolerant to morphine, and A1 adenosine receptor binding activity
      was measured. Treating Sprague-Dawley rats with multiple, increasing doses of
      morphine i.p. for 6 days resulted in an about 10-fold increase in the median
      antinociceptive dose (AD50) of morphine to elicit an antinociceptive response. On
      the other hand, this treatment also caused a 4 to 5-fold increase in the AD50 of
      cyclopentyladenosine (CPA). When A1 adenosine receptor binding was determined by
      using [3H]cyclohexyladenosine ([3H]CHA) a significant decrease in binding (P less
      than 0.05) in the spinal cord but not in the cortex was observed. Scatchard
      analysis of the [3H]CHA saturation binding data revealed a decrease in Bmax
      values (from 185.5 fmol/mg to 110.2 fmol/mg) and no significant change in Kd
      values.

PMID- 1396995
TI  - Antihypertensive and hormonal activity of MK 954 in spontaneously hypertensive
      rats.
AB  - MK 954 (DuP 753), a recently developed angiotensin II (Ang II) receptor
      antagonist, was administered orally for 2 weeks to spontaneously hypertensive
      (SHR) and Wistar-Kyoto rats (WKY). Whereas the basal levels of plasma Ang II were
      lower in SHR than in WKY, treatment with MK 954 markedly reduced blood pressure
      in SHR but not in WKY. Plasma renin activity, Ang I and Ang II were increased,
      while plasma aldosterone was decreased in both strains. These results no only
      indicate therapeutic efficacy of this agent in the chronic treatment of human
      hypertension, but also support the idea that the renin-angiotensin system plays
      an important role in the control of blood pressure in SHR.

PMID- 1396996
TI  - Release of immunoreactive [Met5]enkephalin and cholecystokinin from the spinal
      cord by beta-endorphin administered intraventricularly in the pentobarbital
      anesthetized rat.
AB  - Beta-endorphin (4 micrograms) injected i.v.t. induced the release of
      immunoreactive [Met5]enkephalin and sulfated cholecystokinin octapeptide (CCK-8s)
      from the spinal cord in the pentobarbital-anesthetized rat. The inhibition of the
      tail-flick response induced by beta-endorphin given i.v.t. was antagonized by
      i.t. injection of CCK-8s and potentiated by i.t. administration of the antibody
      to CCK-8s. The findings give support to the hypothesis that endogenous CCK-8s in
      the spinal cord may play a negative feedback role in modulating beta-endorphin
      induced antinociception.

PMID- 1396997
TI  - Striatal dopamine D1-like receptors have higher affinity for dopamine in ethanol
      treated rats.
AB  - Experiments were carried out with brain tissues of ethanol-experienced (long-term
      ethanol intake but withdrawn) vs. ethanol-naive animals. The in vitro 3H
      antagonist binding of [3H]SCH 23390 and of [3H]spiperone to striatal dopamine D1-
      and D2-like receptors revealed no significant changes in KD and Bmax values.
      Displacement of the 3H antagonist binding by dopamine indicated high- and low
      affinity states, which also showed no significant alteration at the D2-like
      receptor but a 5-fold increase of dopamine affinity at the high-affinity state of
      the D1-like receptor of the ethanol-experienced rats.

PMID- 1396998
TI  - Effects of omega-3, omega-6 and omega-9 fatty acids on vascular smooth muscle
      tone.
AB  - The comparative effects of omega-3, omega-6 and omega-9 fatty acids on vascular
      smooth muscle tone were investigated. Docosahexaenoic acid (1-255 microM) and
      eicosapentaenoic acid (31-255 microM) inhibited phenylephrine-induced
      contractions, (8-63%) and (20-65%), respectively, which were not altered by
      indomethacin, NDGA, or by removal of the endothelium. Linoleic acid (18:2n6) and
      arachidonic acid (20:4n6) also induced significant relaxation. Therefore, fatty
      acid-induced relaxation of the rat aorta is specific to polyunsaturated fatty
      acids, 20:5n3, 22:6n3, 18:2n6 and 20:4n6.

PMID- 1396999
TI  - Transmural pressure inhibits nitric oxide release from human endothelial cells.
AB  - We examined the effect of transmural pressure on histamine-stimulated nitric
      oxide release from cultured endothelial cells prepared from human umbilical cord
      veins. PO2 and pH were kept constant throughout the experiments. Various levels
      of transmural pressure and atmospheric pressure (40, 80, 120 and 160 mm Hg) were
      applied. Nitric oxide release was inhibited in a pressure-dependent manner. The
      inhibitory effects were reversible, and nitric oxide had no effect on the
      morphology of the cells. Our results suggest that transmural pressure-mediated
      inhibition of nitric oxide release contributes to pressure-induced
      vasoconstriction and reduced endothelium-dependent relaxation in patients with
      hypertension.

PMID- 1397000
TI  - Effect of naloxone-precipitated morphine withdrawal on noradrenaline release in
      rat hippocampus in vivo.
AB  - Here we investigated the effect of naloxone-precipitated morphine withdrawal on
      the release of noradrenaline in hippocampus of the anaesthetised rat. Naloxone (1
      mg/kg i.p.) injected 3 and 24 h, but not 3 weeks, after eight daily injections of
      morphine, induced an immediate increase in hippocampal noradrenaline release.
      This striking effect of naloxone was markedly attenuated by pretreatment with
      clonidine (0.1 mg/kg s.c.). These findings provide direct evidence for a marked
      release of noradrenaline in hippocampus during opiate withdrawal in vivo.

PMID- 1397001
TI  - C-type natriuretic peptide-22 differentiates between natriuretic peptide
      receptors in rat choroid plexus and subfornical organ.
AB  - Atrial natriuretic peptide (ANP) receptors in the rat choroid plexus and
      subfornical organ were characterized with C-type natriuretic peptide-22 (CNP-22)
      and 125I-Tyr0-CNP-22. The receptor autoradiographic method we used revealed that
      125I-Tyr0-CNP-22 specifically bound to the choroid plexus, but only slightly to
      the subfornical organ, areas densely labeled with 125I-alpha-rat ANP (125I-rANP).
      CNP-22 significantly inhibited 125I-rANP binding to the choroid plexus; however,
      the peptide did not affect 125I-rANP binding to the subfornical organ. Thus, the
      characteristics of ANP receptors in the rat choroid plexus and subfornical organ
      are probably different.

PMID- 1397002
TI  - Inhibition by azelastine of the effects of platelet-activating factor in lungs
      from actively sensitised guinea-pigs.
AB  - The effect of azelastine on platelet-activating factor (PAF)-induced
      bronchoconstriction and mediator release in isolated lungs from actively
      sensitised guinea-pigs was investigated. Guinea-pigs were actively sensitised
      with two s.c. injections of 10 micrograms ovalbumin in 1 mg Al (OH)3 at a 2-week
      interval. One week after the second injection, the lungs were removed and
      challenged intra-arterially with PAF or arachidonic acid. In some experiments
      lungs from non-immunised guinea-pigs were injected with PAF or histamine.
      Bronchoconstriction, the release of thromboxane (TX)B2 or leukotriene (LT)-like
      material and the histamine content of the effluent were evaluated. Azelastine was
      given s.c. at 10 or 100 micrograms/kg, 4 h before lung removal. Azelastine (100
      micrograms/kg) did not inhibit PAF-induced bronchoconstriction and mediator
      release from lungs from non-immunised guinea-pigs. In contrast, the
      hyperresponsiveness to 1 ng PAF observed in lungs from actively sensitised
      animals was dose dependently inhibited by azelastine. Azelastine did not reduce
      the histamine-induced bronchoconstriction and consequent TXB2 release from lungs
      from immunised guinea-pigs, indicating that the protective effect exerted against
      hyperresponsiveness to PAF was not due to histamine antagonism. Azelastine also
      reduced arachidonic acid-induced bronchoconstriction and LT-like material release
      from sensitised lungs, regardless of the presence of indomethacin. These results
      suggest that inhibition of lung hyperresponsiveness to PAF by azelastine may
      result from an interference with leukotriene synthesis.

PMID- 1397003
TI  - Effects of systemic morphine on diffuse noxious inhibitory controls: role of the
      periaqueductal grey.
AB  - The effects of systemic morphine (1 mg/kg i.v.) on diffuse noxious inhibitory
      controls (DNIC) were studied in both sham-operated animals and those with
      quinolinic acid-induced lesions of the periaqueductal grey (PAG). DNIC acting on
      convergent neurones in the dorsal horn of the spinal cord were similar in the
      sham-operated and lesioned animals. However, following morphine injection, DNIC
      were blocked in the sham-operated but not in the PAG-lesioned animals. It is
      concluded that, although the PAG is not directly involved in the supraspinal loop
      subserving DNIC, it can modulate these controls. In addition, as naloxone
      reversed the effects of morphine in the control group but reduced DNIC in the PAG
      lesioned animals, it is suggested that more than one opioidergic system is
      involved in DNIC.

PMID- 1397004
TI  - Effect of SR 27417 on oedema formation induced in rabbit skin by platelet
      activating factor or antigen.
AB  - SR 27417, the first member of a newly developed series of platelet activating
      factor (PAF) antagonists inhibited in a dose-dependent manner PAF-induced oedema
      formation in rabbit skin when administered i.d. premixed with PAF (ED50 = 3.3 +/-
      0.15 pmol/site i.d. (intradermally) (n = 5). The effect of SR 27417 was over 660
      times more potent than that of the triazolothienodiazepine, WEB-2086 (ED50 = 5.4
      +/- 0.71 nmol/site i.d.) (n = 5). SR 27417 protected rabbits from PAF-induced
      plasma extravasation with an ED50 value of 16 +/- 3 micrograms/kg when given i.v.
      1 h before PAF challenge. It was also effective when given p.o. 3 h before PAF
      i.d. administration (ED50 = 0.18 +/- 0.07 mg/kg p.o.) (n = 5). This effect of SR
      27417 was selective for PAF since inflammatory responses induced by other
      mediators (bradykinin, histamine, N-formyl-L-methionyl-L-leucyl-L-phenyl-alanine,
      leukotriene B4) were not affected. After i.v. or oral administration (1 and 5
      mg/kg respectively) SR 27417 had an extended duration of activity (between 72 and
      96 h). In presensitized rabbits, SR 27417 premixed with the allergen inhibited
      dose-dependently allergen-induced plasma exudation (ED50 = 12 +/- 0.08 nmol/site
      i.d.) (n = 5) (vs. 850 +/- 98 nmol/site (n = 5) for WEB-2086). Similarly, i.v.
      injection of SR 27417 (1 mg/kg i.v.) inhibited allergen-induced vascular
      permeability. These results confirm that PAF plays a major role in the
      development of cutaneous anaphylaxis and that SR 27417 may be an effective
      prophylactic drug.

PMID- 1397005
TI  - Protective effect of bepridil against veratrine-induced contracture in rat atria.
AB  - In isolated stimulated rat atria, superfusion with veratrine caused a marked
      contracture (VIC) which was absent in calcium-free medium and which was inhibited
      by tetrodotoxin (IC50VIC of 1.38 microM). Lowering the extracellular calcium
      concentration from 2.5 to 0.5 or 0.1 mM reduced the veratrine-induced contracture
      and delayed its onset. Superfusion of bepridil (1-10 microM) for 60 min before
      and during veratrine exposure markedly slowed the onset of contracture, reduced
      the maximum response (IC50VIC = 2.11 microM) and facilitated recovery upon
      washout of the alkaloid. The direct negative inotropic effect (NIE) of bepridil
      (IC50NIE = 10.96 microM) resulted in an VIC/NIE ratio of 5.19 for this drug. The
      protective effects of bepridil were rate-independent and were not modified by the
      presence of atropine (1.4 microM) and propranolol (0.3 microM) in the medium.
      Diltiazem, verapamil and nifedipine only reduced veratrine-induced contracture at
      concentrations much higher than those producing a negative inotropic effect,
      giving them negative NIE/VIC ratios of 0.31, 0.08 and 0.08 respectively. Like
      bepridil, flunarizine had a positive NIE/VIC ratio (15.87, IC50VIC = 3.71
      microM). The lack of effect of the quaternary derivative of bepridil CERM 11888
      indicated that intracellular sites of action may be involved in the activity of
      bepridil on veratrine-induced contracture. Given that veratrine-induced changes
      may mimic some of the pathological changes occurring in ischaemia, the results
      suggest that bepridil and flunarizine may be more effective than L-type, slow
      calcium ion-channel blockers in protecting against calcium overload during
      ischaemia and reperfusion injury.

PMID- 1397006
TI  - Blockade by trifluoperazine of a Ca(2+)-activated K+ channel in rat hippocampal
      pyramidal neurons.
AB  - The effects of trifluoperazine, a phenothiazine derivative, on the large
      conductance Ca(2+)-activated K+ channel (BKCa) in dissociated rat hippocampal
      pyramidal neurons were examined using the inside-out configuration of the patch
      clamp technique. The BKCa was activated by 12.6 microM Ca2+ on the internal
      surface of the membrane patch. The single channel conductance of the BKCa was 244
      +/- 17.5 pS (n = 10) in symmetrical solutions of 150 mM K+. Trifluoperazine,
      applied on the internal surface of the membrane, decreased the open probability
      of the channel without changing the single channel conductance. The reduction in
      the open probability was well described by a block of the open state of the
      channel in a simple sequential model. The apparent dissociation constant (KD) for
      the reduction was calculated to be 1.4 microM and the Hill coefficient 0.69 at
      +20 mV. The inhibition was voltage dependent, being more pronounced at
      depolarized voltages. The voltage dependence enabled us to estimate that the
      binding site for the agent in the channel lies about half way across the membrane
      electrical field. It is concluded that trifluoperazine blocks the open state of
      the BKCa, which is known to provide an outward current for repolarization and
      afterhyperpolarization of the neuronal action potential. This may result in a
      decrease in spike intervals during burst firing of neurons.

PMID- 1397007
TI  - Antagonism by beta-eudesmol of neostigmine-induced neuromuscular failure in mouse
      diaphragms.
AB  - beta-Eudesmol, a sesquiterpenol extracted from a Chinese herb, Atractylodes
      lancea, at 10-80 microM, did not affect muscle action potentials, miniature and
      evoked endplate potentials and acetylcholine-induced depolarization in the
      presence or absence of neostigmine in mouse phrenic nerve-diaphragms. However,
      the tetanic fade, muscle fasciculation and twitch potentiation induced by
      neostigmine were effectively antagonized by 20 microM beta-eudesmol. When trains
      of pulses were applied to the nerve in the presence of neostigmine, beta-eudesmol
      reduced the incidence of explosive depolarization of the endplate from 95% to 35
      67% of junctions, and shortened the duration when it occurred. Moreover, both the
      maximal and steady-state depolarizations during repetitive stimulation were
      reduced while the amplitudes of steady-state endplate potentials were increased.
      The results suggest that beta-eudesmol antagonized neostigmine-induced
      neuromuscular failure mainly by a presynaptic action to depress the regenerative
      release of acetylcholine during repetitive stimulation. The mechanism of
      antagonism is obviously not tubocurarine-like and it is unrelated to
      desensitization of acetylcholine channels.

PMID- 1397008
TI  - Characterization of antigastrin activity in vivo of CR 2194, a new R-4-benzamido
      5-oxo-pentanoic acid derivative.
AB  - The antigastrinic activity, in vivo, of CR 2194 (R-4-(3-chlorobenzamido)-5-(8
      azaspiro[4.5]decan-8-yl) -5-oxo pentanoic acid) was assessed in various animal
      species. CR 2194 antagonized pentagastrin-stimulated gastric acid secretion in
      the rat (ID50 = 11 mg/kg i.v.), dog (ID50 = 5.9 mk/kg i.v. or 28.8 mg/kg os) and
      cat (ID50 = 15.5 mg/kg i.v.). CR 2194, in the cat, inhibited both competitively
      and non-competitively the gastric acid secretion stimulated with increased doses
      of pentagastrin, with a pA2 of 4.89. In the rat and in the dog the antagonism
      seemed to be non-competitive and the respective pD'2 calculated were 4.54 and
      4.42. The interaction of CR 2194 with the gastrin receptors appeared reversible,
      as demonstrated by the return to normal values of the acid output after the
      conclusion of the i.v. infusion, during pentagastrin continuous stimulation in
      the dog. The antigastrin activity was specific: CR 2194 was unable to antagonize
      the gastric acid secretion stimulated by carbachol or histamine in the rat up to
      the dose of 100 mg/kg. CR 2194 was effective to antagonize the gastric acid
      secretion stimulated by gastrin release after meal ingestion in the Heidenhain
      pouch dog model. The ID50 calculated was 2.89 mg/kg after oral administration.
      All these characteristics make CR 2194 an important compound in the investigation
      of the biological effects of gastrin and a potential agent for diagnostic or
      therapeutic use.

PMID- 1397009
TI  - Pharmacological assessment of Ca2+ dependence of endothelin-1-induced response in
      rat aorta.
AB  - In rat aorta, endothelin-1 (ET-1) induced a slowly developing and sustained
      contraction in Ca(2+)-containing normal Krebs, nominally Ca(2+)-free Krebs, and
      Ca(2+)-free Krebs containing EGTA with a decreasing level of contraction. When ET
      1-precontracted tissues were washed with Ca(2+)-free Krebs +50 microM EGTA, the
      tissues spontaneously and slowly relaxed. Readministration of Ca2+ during the
      early spontaneous relaxation phase caused a rapidly developing tonic contraction.
      When added during the late spontaneous relaxation phase, Ca2+ evoked slowly
      developing or, sometimes, biphasic contractions. In the presence of sarcoplasmic
      reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, the above biphasic
      contraction brought about by readministration of Ca2+ converted to a rapidly
      developing monophasic response. Thus, the first component of the biphasic
      contraction may be due to refilling of ET-1-sensitive Ca2+ store via the internal
      membrane Ca(2+)-pump. Furthermore, the ability of the phenylephrine-sensitive
      pool of internal Ca2+ to refill in the presence of 10(-8) M ET-1 suggests that
      the phenylephrine-sensitive pool differs from ET-1-sensitive pool and cannot be
      depleted by ET-1.

PMID- 1397011
TI  - Displacement of in vivo binding of [3H]brofaromine to rat intestinal monoamine
      oxidase A by orally administered tyramine.
AB  - The reversibility of the interaction of inhibitors with monoamine oxidase (MAO)
      is thought to provide a safety valve with respect to tyramine potentiation. We
      sought experimental evidence for this concept by studying the binding of orally
      administered [3H]brofaromine to the A-form of MAO in the rat ileum. Specific
      binding, defined by pretreatment with 10 mg/kg clorgyline p.o., amounted to 70
      90% of total binding between 30 min and 6 h after administration of the
      radioligand. Brofaromine and clorgyline dose dependently displaced
      [3H]brofaromine with ED50 values of about 0.2 mg/kg when administered orally
      after the radioligand; so did orally administered tyramine in doses relevant for
      tyramine potentiation in the rat. It was also found that tyramine was relatively
      more effective in partially MAO-inhibited rats. The data suggest that the concept
      of reversibility functioning as a safety valve with respect to the potentially
      hazardous effects of tyramine ingestion is realistic.

PMID- 1397010
TI  - Relative agonist potencies of C2-substituted analogues of adenosine: evidence for
      adenosine A2B receptors in the guinea pig aorta.
AB  - Nine C2-substituted adenosine analogues that are potent and selective for the A2
      adenosine receptor were tested for their ability to induce relaxations of the
      guinea pig aorta. Compounds tested were 2-phenylethoxyadenosine (PEA), 2
      phenylethoxy-5'-N-ethylcarboxamidoadenosine (PENECA), 2-cyclohexylethoxyadenosine
      (CEA), 2-fluorophenylethoxyadenosine (FPEA), 2-methoxyphenylethoxyadenosine
      (MPEA), 2-naphthylethoxyadenosine (NEA), 2-phenylaminoadenosine (CV-1808), 2
      phenylethylaminoadenosine (PEAA) and 2-carboxyethylphenethylamino-5'-N
      ethylcarboxamidoadenosine (CGS21680). The responses to these agents were compared
      to those of three standard adenosine receptor agonists, 5'-N
      ethylcarboxamidoadenosine (NECA), N6-cyclohexyladenosine (CHA) and R-N6
      phenylisopropyladenosine (R-PIA). The C2-ethoxyadenosine analogues were 30- to
      140-fold less potent than NECA and the C2-amino-substituted analogues were 250 to
      1000-fold less potent than NECA at inducing relaxations of the guinea pig aorta.
      All of the analogues were also less potent than the A1-selective agonist R-PIA.
      However, only responses to NECA were competitively antagonized by the non
      selective adenosine receptor antagonist 8-phenyltheophylline (8-PT), pKB = 6.83
      +/- 0.05. The results suggest that the C2-substituted analogues produce
      relaxations of the guinea pig aorta through a combination of actions at A2
      adenosine receptors and at xanthine resistant sites. The lack of potency of these
      analogues at activating the xanthine sensitive A2-receptors in the guinea pig
      aorta suggests that these adenosine receptors may be of the A2b-subtype.

PMID- 1397012
TI  - Involvement of the cholinergic system in the effects of nefiracetam (DM-9384) on
      carbon monoxide (CO)-induced acute and delayed amnesia.
AB  - The effects of N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)-acetamide (DM
      9384, nefiracetam), a cyclic derivative of GABA, were investigated in the carbon
      monoxide (CO)-induced amnesia model in mice using the passive avoidance task.
      Memory deficiency occurred when mice were exposed to CO before memory was
      completely consolidated after training (acute amnesia), at 7 days before training
      and 7 days after training (delayed amnesia). DM-9384 prolonged the step-down
      latency in mice with CO-induced amnesia. Scopolamine blocked the anti-amnesic
      effect of DM-9384 on delayed amnesia that had been induced by pre- or post
      training exposure to CO. Bicuculline had a tendency to antagonize the anti
      amnesic effect of DM-9384, but this tendency was not significant. Under these
      conditions, no significant change in the activity of choline acetyltransferase
      and glutamic acid decarboxylase was observed in the frontal cortex, striatum and
      hippocampus. These results suggest that DM-9384 potentiates cholinergic neuronal
      function and that it may modify acquisition and/or consolidation of memory.

PMID- 1397013
TI  - Mechanical and ionic response of rat aorta to diazoxide.
AB  - Diazoxide provoked concentration-dependent and endothelium-independent
      relaxations of the mechanical responses evoked by low concentrations of KCl.
      Glibenclamide, tolbutamide and tetraethylammonium shifted the concentration
      response curve for diazoxide to the right. The drug also caused a dose-dependent
      stimulation of 86Rb outflow which was inhibited by glibenclamide and tolbutamide.
      Diazoxide (10(-4) and 10(-3) M) inhibited the contractions elicited by 10(-1) M
      K+ and provoked a concentration-dependent reduction in the contractile responses
      to Ca2+. Diazoxide also reduced the KCl (8 x 10(-2) M)-induced increase in 45Ca
      outflow. These data indicate that the vasorelaxant properties of diazoxide are
      probably related to an inhibition of Ca2+ entry into smooth muscle cells. The
      reduction in Ca2+ entry appears to result from K+ channel activation. At high
      concentrations, diazoxide also exhibited antagonistic actions on voltage
      sensitive Ca2+ channels.

PMID- 1397014
TI  - Hyperglucagonemia induced in mice by tryptamine: involvement of the peripheral 5
      HT2 receptors.
AB  - The effects of an indoleamine, tryptamine, on plasma glucagon levels were
      investigated in mice. Tryptamine induced dose-related increases in plasma
      glucagon levels. The hyperglucagonemia effects of tryptamine were completely
      antagonized by methysergide and ketanserin which have a high affinity to 5-HT2
      receptors. In addition, the peripheral 5-HT2 receptor antagonist, xylamidine,
      also strongly inhibited tryptamine-induced hyperglucagonemia. Our results
      indicate that the peripheral 5-HT2 receptors mediate the increase in plasma
      glucagon levels induced by tryptamine and that these receptors may have a role in
      the control of glucagon secretion.

PMID- 1397015
TI  - Contractile activity of vasotocin, oxytocin, and vasopressin on mammalian
      prostate.
AB  - The neurohypophyseal peptides arginine vasotocin, oxytocin and arginine
      vasopressin contracted guinea pig, rat, canine and human prostates with potencies
      and efficacies that were comparable to those of noradrenaline and methacholine.
      All three neuropeptides raised prostatic tone and elicited contractions at 10(-9)
      or 10(-8) M, with an order of efficacy: arginine vasotocin greater than oxytocin
      greater than arginine vasopressin. The findings suggest a physiological role for
      these peptides in prostatic smooth muscle contraction and possibly also in other
      aspects of male reproductive function.

PMID- 1397016
TI  - PF-5901 inhibits gastrointestinal platelet-activating factor synthesis in vivo.
AB  - PF-5901, a novel anti-inflammatory compound, has previously been shown to inhibit
      the synthesis of platelet-activating factor (PAF) by peritoneal mast cells in
      vitro. The purpose of the present study was to assess the effects of this
      compound on PAF synthesis in vivo using two animal models which are characterized
      by elevated levels of gastrointestinal PAF synthesis. In the first study, rats
      were infected with Nippostrongylus brasiliensis and killed 17 days later. Groups
      of infected rats were given PF-5901 at doses ranging from 0.1 to 100 mg/kg, and
      12 h later the effects on jejunal PAF synthesis were determined. PF-5901 reduced
      PAF synthesis in a concentration-dependent manner, with inhibition reaching 95%
      at the highest dose tested. In the second study, groups of rats were orally
      pretreated with PF-5901 (100 mg/kg) or vehicle 3 or 12 h prior to induction of
      endotoxic shock by i.v. administration of lipopolysaccharide from Salmonella
      typhosa. PAF synthesis in various regions of the gastrointestinal tract was
      assessed 15 min later. PF-5901 significantly reduced the hemoconcentration, but
      not the hypotension associated with endotoxic shock. Moreover, this compound
      significantly inhibited PAF synthesis in all tissues studied when a 12 h
      pretreatment time was used, and in all tissues except the duodenum when a 3 h
      pretreatment time was used. These studies demonstrate that PF-5901 inhibits
      gastrointestinal PAF synthesis in two in vivo models. This compound may therefore
      be a useful pharmacological tool for future studies on the role of PAF in
      inflammatory processes, and the effects of PF-5901 on PAF synthesis may
      contribute to its anti-inflammatory properties.

PMID- 1397017
TI  - Effects of verapamil on [3H]acetylcholine release in the striatum of
      spontaneously hypertensive rats.
AB  - In the present study, we describe the effects of Ca2+ channel antagonist
      (verapamil) on [3H]acetylcholine (ACh) release in the central nervous system of
      spontaneously hypertensive rats (SHR). The electrically stimulated release of
      [3H]ACh from striatal slices was not different between SHR and normotensive
      Wistar Kyoto (WKY) rats. Verapamil inhibited electrically stimulated [3H]ACh
      release in a dose-related fashion. The inhibitory effect of verapamil was
      significantly greater in SHR than in WKY rats. These results suggest that the
      Ca2+ sensitivity of central cholinergic neurons might be enhanced in SHR, which
      could attribute, at least partially, to the pathogenesis of hypertension.

PMID- 1397018
TI  - 8-Methoxypsoralen blocks ATP-sensitive potassium channels and stimulates insulin
      release.
AB  - 8-Methoxypsoralen (8-MOP) stimulated insulin release from HIT-T15 B-cells and
      inhibited the diazoxide-induced and sulfonylurea-sensitive 86Rb+ efflux from
      these cells. These results indicate that 8-MOP affects ATP-sensitive K+ channel
      activity. Patch-clamp experiments confirmed this view.

PMID- 1397019
TI  - Hippocampal lesions induced by microinjection of the nitric oxide donor
      nitroprusside.
AB  - Unilateral intrahippocampal microinjection of the nitric oxide (NO) donor, sodium
      nitroprusside (33 nmol in 1 microliter), in the rat resulted in a marked
      degeneration of the ipsilateral hippocampal formation characterised by a virtual
      absence of pyramidal cells and dentate granule cells. Damage was not observed
      contralateral to the injection site. Quinolinic acid (100 nmol in 1 microliter)
      also produced neuronal damage within the ipsilateral hippocampus although the
      lesion was considerably smaller and more discrete than that caused by sodium
      nitroprusside. Injection of equimolar amounts of potassium ferricyanide failed to
      mimic the neurotoxic effects of sodium nitroprusside suggesting that NO is
      responsible specifically for the neuronal damage observed.

PMID- 1397020
TI  - Activation of metabotropic receptors has a neuroprotective effect in a rodent
      model of focal ischaemia.
AB  - The role of the glutamate 'metabotropic' receptor was investigated in an
      experimental model of focal ischaemia-induced neurodegeneration. The metabotropic
      agonist, trans-1-amino cyclopentane-1,3-dicarboxylic acid (t-ACPD, 20 mg/kg
      i.p.), was administered to mice immediately after middle cerebral artery
      occlusion (MCAO), which causes cerebral infarct. Seven days after MCAO, the mean
      infarct volume value of the t-ACPD-treated group (mean +/- S.E. = 4.57 +/- 0.73
      mm3) was significantly reduced, by 34.3%, compared to the vehicle-treated group
      (mean +/- S.E. = 6.95 +/- 0.59 mm3, P less than 0.01). This suggests that
      metabotropic receptor activation in the adult brain reduces excitotoxicity.

PMID- 1397021
TI  - Competitive NMDA receptor antagonists attenuate phencyclidine-induced excitations
      of A10 dopamine neurons.
AB  - The binding of phencyclidine (PCP) within the channel gated by the NMDA-receptor
      complex can be positively or negatively modulated by compounds which facilitate
      or prevent the interaction of glutamate to the NMDA recognition site. In the
      present study extracellular recordings were used to evaluate the possibility that
      the negative modulation of NMDA channel function by the competitive NMDA
      antagonists (+/-)-CPP (3-((+/-)2-carboxypiperazin-4- yl)propyl-1-phosphonate) and
      CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylate) could affect the
      response of A10 dopamine neurons to PCP. Pretreatment with 40 mg/kg of (+/-)-CPP
      or CGS 19755 completely blocked the low-dose excitatory effects of PCP, whereas
      10 mg/kg of CGS 19755 produced only a partial blockade. However, neither CGS
      19755 or (+/-)-CPP affected the amount of attenuation of A10 firing occurring
      with large doses of PCP. (+/-)-CPP and CGS 19755 pretreatment also failed to
      alter the morphine-induced stimulation of dopamine activity. These findings not
      only provide further evidence that the low-dose PCP-induced activation of A10
      neurons is mediated through the NMDA-ion channel complex, but suggest that some
      physiological or behavioral effects evoked by PCP might be prevented by treatment
      with competitive NMDA receptor blockers.

PMID- 1397023
TI  - Dopamine and melatonin in the nucleus accumbens may be implicated in the mode of
      action of antidepressant drugs.
AB  - The effect of chronic systemic treatment (once a day for 2-3 weeks) with
      different antidepressant drugs (desipramine, mianserin, fluvoxamine 15 mg/kg per
      day i.p. or s.c.) on the behavioral responses elicited by intra-accumbens
      injection of graded doses (1-10,000 ng) of apomorphine and two doses (10 and 100
      ng) of melatonin was investigated in rats. Treatment with antidepressant drugs
      consistently facilitated apomorphine-induced hypermotility, but differentially
      influenced apomorphine-induced hypomotility. The drugs completely antagonized
      melatonin-induced behavioral changes (hypomotility and increased duration of
      sniffing). The data suggest that chronic treatment with antidepressant drugs
      results in postsynaptic dopamine receptor supersensitivity in the nucleus
      accumbens, a terminal area of the mesolimbic dopaminergic system. It is
      postulated that the development of supersensitivity may be mediated by the
      inhibition of melatonin-induced effects observed after acute and chronic
      treatment with these antidepressants. The present findings may be relevant for
      the mode of therapeutic action of antidepressant drugs.

PMID- 1397022
TI  - Effects of BY-1949 on evoked responses of cortical blood flow and Meynert
      neurons.
AB  - The effects of BY-1949, a novel dibenzoxazepine derivative, injected into the
      cerebral ventricle on noxious stimulus-induced responses of regional blood flow
      in the cortex and neuronal activity in the nucleus basalis of Meynert were
      studied in male rats. These induced responses were markedly enhanced by
      administration of BY-1949 (16.4 +/- 0.5 ng/100 g, S.E.M.). These data indicate
      that BY-1949 acts on the central nervous system to modulate the response to a
      noxious stimulus of regional cerebral blood flow and neuronal activity in the
      nucleus basalis of Meynert.

PMID- 1397024
TI  - Involvement of a phosphoramidon-sensitive endopeptidase in the processing of big
      endothelin-1 in the guinea-pig.
AB  - In anaesthetized and ventilated guinea-pigs, i.v. injection of 1 nmol/kg big
      endothelin-1 (big ET-1) did not evoke significant changes in pulmonary inflation
      pressure (PIP) and mean arterial blood pressure (MBP), whereas injection of the
      same dose of endothelin-1 (ET-1) induced marked and rapid bronchoconstrictor and
      pressor responses. Administered at the dose of 10 nmol/kg, big ET-1 provoked
      significant increases in PIP and MBP, which developed slowly and were long
      lasting as compared to those evoked by ET-1. When big ET-1 was incubated for 45
      min at 37 degrees C with alpha-chymotrypsin (2 mU/nmol) or pepsin (1
      microgram/nmol) and then injected into guinea-pigs at the dose of 1 nmol/kg,
      marked bronchoconstrictor and pressor responses were observed, with kinetics
      similar to those noted after administration of the same dose of ET-1. The
      magnitude of the alpha-chymotrypsin- or pepsin-treated big ET-1 responses was
      similar to that induced by ET-1, incubated or not with the enzymes. Injected i.v.
      at the dose of 5 mg/kg, 5 min before the challenge, phosphoramidon almost totally
      inhibited the bronchoconstrictor and pressor responses induced by 10 nmol/kg big
      ET-1, whereas thiorphan (5 mg/kg) partially reduced the increase in PIP and
      exerted a minimal effect on the changes in MBP. Administered at the dose of 20
      mg/kg per os, 1 h before i.v. administration of 10 nmol/kg big ET-1, enalapril
      maleate and captopril did not significantly alter the bronchoconstriction and the
      hypertensive response evoked by the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397025
TI  - Endothelin-1-induced prostaglandin E2 production: modulation of contractile
      response to endothelin-1 in porcine coronary artery.
AB  - Endothelin-1 (ET-1, 1 nM) increased the release of prostaglandin E2 (PGE2) in
      endothelium-denuded smooth muscle strips of porcine coronary arteries.
      Indomethacin enhanced the amplitude of contraction induced by ET-1 and inhibited
      the stimulated release of PGE2. PGE2 (0.1-100 nM) attenuated the amplitude of
      contraction induced by 1 nM ET-1. These results suggest that in the smooth muscle
      of porcine coronary arteries, ET-1 increased the synthesis of PGE2, which
      functionally antagonizes the direct vasoconstrictor actions of ET-1.

PMID- 1397026
TI  - Acetyl-L-carnitine releases dopamine in rat corpus striatum: an in vivo
      microdialysis study.
AB  - The effect of acetyl-L-carnitine, a compound reported to be beneficial for senile
      patients, on the release of dopamine (DA) from the striatum was studied by using
      in vivo brain dialysis in anesthetized rats coupled with HPLC-electrochemical
      detection. Striatal infusion of acetyl-L-carnitine increased the efflux of DA
      with no apparent changes in efflux of DA metabolites, 3,4-dihydroxyphenylacetic
      acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA). The DA-releasing
      effect of acetyl-L-carnitine was concentration- and Ca(2+)-dependent, and was
      abolished by omega-conotoxin fraction GVIA and tetrodotoxin, inhibitors of the
      voltage-dependent Ca2+ and Na+ channels, respectively. Nomifensine, an inhibitor
      of DA reuptake did not alter the DA-releasing property of acetyl-L-carnitine. DA
      released from the striatum by acetyl-L-carnitine was decreased by reserpine
      pretreatment whereas the d-amphetamine-evoked DA outflow was not affected. In
      contrast to acetyl-L-carnitine, d-amphetamine reduced the extracellular
      concentrations of DOPAC and HVA. We conclude from the present data that acetyl-L
      carnitine evokes DA release from the vesicular pools of the nigrostriatal
      dopaminergic neurons by a Ca(2+)-dependent, exocytotic process.

PMID- 1397028
TI  - Decreased activity of rat A10 dopamine neurons following withdrawal from repeated
      cocaine.
AB  - Electrophysiological techniques were used to determine the basal activity of A10
      dopamine (DA) neurons in the rat ventral tegmental area after a 10-14 day
      withdrawal from repeated cocaine treatment (10.0 mg/kg i.p. twice daily for 14
      days). The number of spontaneously active A10 DA cells was significantly
      decreased (42%) in the cocaine-treated rats. This decreased activity may underlie
      the diminished basal levels of synaptic DA within the nucleus accumbens
      previously reported in cocaine-withdrawn rats and may account for anhedonia,
      anergia and cocaine craving reported by withdrawn cocaine addicts.

PMID- 1397027
TI  - Discriminative stimulus properties of the muscarinic receptor agonists Lu 26-046
      and O-Me-THPO in rats: evidence for involvement of different muscarinic receptor
      subtypes.
AB  - The discriminative cues induced by the muscarinic receptor agonists Lu 26-046 ((
      )-7-methyl-3(2-propynyloxy)-4,5,6,7-tetrahydroisothiazolo [4,5-c]pyridine ) and O
      Me-THPO (3-methoxy-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine) were investigated.
      The results were compared with those obtained for the binding profiles of these
      agonists at central muscarinic receptors and with results concerning their
      functional effects at peripheral muscarinic receptors in vitro. Lu 26-046 had
      preferential affinity for M1 versus M2 receptors (Ki index [3H]quinuclidinyl
      benzilate ([3H]QNB/[3H]pirenzepine 4.2) and had partial agonistic activity at M1
      and M2 receptors in rat superior cervical ganglion and guinea pig left atrim,
      respectively. A weak antagonistic effect at M3 receptors in guinea pig ileum was
      observed. O-Me-THPO had non-selective agonistic effects at peripheral M1, M2 and
      M3 receptors and had a slight preference for central M2 receptors in binding
      experiments (M2/M1 index 0.31). Lu 26-046 dose dependently substituted for Lu 26
      046 and partially substituted for O-Me-THPO in rats trained to discriminate Lu 26
      046 and O-Me-THPO from saline, respectively. The (+)-enantiomer of Lu 26-046, Lu
      26-047, had weak partial M1 agonistic activity and M2/M3 antagonistic effects at
      peripheral receptors. Lu 26-047 also had a high M2/M1 index (9.3) in binding
      experiments. Lu 26-047 substituted for Lu 26-046, but preferentially inhibited
      the effect of O-Me-THPO. Pilocarpine had a preferential effect in Lu 26-046
      trained rats, while oxotremorine and arecoline had preferential effects in O-Me
      THPO-trained rats. Large increases in latency times or a disruption of responding
      was generally observed. These compounds were full agonists at peripheral M1, M2
      and M3 receptors. The muscarinic receptor antagonist scopolamine antagonized the
      effect of O-Me-THPO and partially inhibited the effect of Lu 26-046. Scopolamine
      partially substituted for Lu 26-046. The quaternary muscarinic receptor agonist N
      methyl atropine had no effect, indicating that the cues are mediated by central
      muscarinic receptors. It is suggested that the discriminative cues of Lu 26-046
      and O-Me-THPO are preferentially mediated by central M1 (partial) and M2 receptor
      stimulation, respectively. The role of central M3 receptors is not known.

PMID- 1397029
TI  - Dopamine transport: pharmacological distinction between the synaptic membrane and
      the vesicular transporter in rat striatum.
AB  - The pharmacological properties of the monoamine transporters in the synaptic
      vesicles and of the dopamine transporters in the synaptic plasma membrane were
      compared. Tetrabenazine, an inhibitor of the vesicular transporter did not block
      ligand binding to the plasma membrane transporter. Various potent cocaine
      analogues and other compounds active at the plasma membrane transporter did not
      block ligand binding to the vesicular transporter. These data indicate
      pharmacological differences between the vesicular and synaptic membrane
      transporters.

PMID- 1397030
TI  - The effect of calcium channel modulators on blood pressure and pressor responses
      to noradrenaline in the guinea-pig.
AB  - Selective L-type voltage-operated calcium channel (VOCC) antagonists nicardipine,
      diltiazem and verapamil all produced pronounced falls in mean arterial blood
      pressure (MAP) in the anaesthetized artificially ventilated guinea-pig. This fall
      in MAP was associated with a significant reduction of the pressor response
      induced by i.v. noradrenaline. omega-Conotoxin GVIA (CgTx) a preferential N-type
      VOCC antagonist produced a significant time-dependent fall in MAP, similar in
      magnitude to the L-type VOCC antagonist, but did not affect the noradrenaline
      induced pressor responses.

PMID- 1397031
TI  - Preferential small arteriolar vasodilatation by the potassium channel opener, BRL
      38227, in conscious spontaneously hypertensive rats.
AB  - The microvascular effects of the potassium channel opener, BRL 38227 (the active
      enantiomer of cromakalim), were investigated in conscious spontaneously
      hypertensive rats (SHR) provided with a chronic dorsal microcirculatory chamber.
      BRL 38227 decreased blood pressure and increased heart rate in a dose-dependent
      manner. It dilated arterioles of different sizes, with the most pronounced effect
      on the smallest precapillary arterioles. Venule diameters were not significantly
      affected by BRL 38227. The data show a preferential sensitivity of small
      precapillary arterioles for potassium channel opening.

PMID- 1397032
TI  - Neuroprotective effects of NG-nitro-L-arginine in focal stroke in the 7-day old
      rat.
AB  - Recent evidence in primary neuronal cell culture implicates nitric oxide (NO) as
      a mediator of glutamatergic neurotoxicity acting via N-methyl-D-aspartate (NMDA)
      receptors. We find that administration of the potent nitric oxide synthetase
      (NOS) inhibitor NG-nitro-L-arginine (NO-Arg) at 50 mg/kg to 100 mg/kg i.p. to 6
      day old Sprague-Dawley rat pups results in prompt and long-lasting in vivo
      inhibition of NOS. Fifteen hours after administration, NO-Arg produces
      essentially complete neuroprotection against hypoxic-ischemic in a standard (Rice
      Vanucci) model. These results support the hypothesis that NO may play a key
      mediatory role in brain damage attending focal ischemic stroke.

PMID- 1397033
TI  - Effect of Ca2+ modulators on acetylcholine-induced phasic and tonic contractions
      and A23187-induced contractions in ileal longitudinal muscle and IP3 production.
AB  - The influence of different sources of Ca2+ on the Emax and ED50 values of
      acetylcholine (ACh)-induced phasic and tonic contractions and on A23187-induced
      contractions was studied using different extracellular Ca2+ concentrations
      ([Ca2+]o) and the Ca2+ modulators TMB-8 and D600. IP3 production induced by both
      stimulants was also studied. The results are compatible with: (a) the
      mobilization of Ca2+ from an intracellular source as a primary event in the
      phasic response. (b) The primary involvement of a D600-sensitive inward Ca2+
      current in the ACh-tonic response. (c) An inward D600-sensitive Ca2+ current
      associated with the ionophore transported ion. (d) The involvement of an IP3
      independent, TMB-8 sensitive mechanism of Ca2+ mobilization involved in the
      A23187-induced responses.

PMID- 1397034
TI  - Characterization of BIBS 39 and BIBS 222: two new nonpeptide angiotensin II
      receptor antagonists.
AB  - Two new nonpeptide angiotensin II (AII) receptor antagonists, 4'-[(2-n-butyl-6
      cyclohexylaminocarbonylamino-benzimidazole-1-yl)- methyl ] biphenyl-2-carboxylic
      acid (BIBS 39) and 2-n-butyl-1-[4-(6-carboxy-2,5-dichlorobenzoylamino)-benzyl]-6
      N- (methylaminocarbonyl)-n-pentylamino-benzimidazole (BIBS 222) were
      characterized in radioligand binding assays, and in vitro and in vivo
      experiments. BIBS 39 displaced [125I] AII from its specific binding sites with a
      K(i) value of 29 +/- 7 nM for the AII subtype I (AT1) receptor and a K(i) value
      of 480 +/- 110 nM for the AII subtype 2 (AT2) receptor. BIBS 222 showed a K(i)
      value of 20 +/- 7 nM for the AT1 subtype and a K(i) value of 730 +/- 170 nM for
      the AT2 subtype. Thus BIBS 39 was 17 times more selective for the AT1 subtype and
      BIBS 222 37 times. Both compounds were specific for AII receptors as they did not
      show high affinity for other receptors. BIBS 39 shifted the AII concentration
      contractile response curves in isolated rabbit aorta to the right in a parallel
      fashion. A pA2 value of 8.14 +/- 0.08 and a slope of 1.06 +/- 0.07 were
      calculated. BIBS 222 caused nonparallel shifts to the right and reduced the
      maximal response induced by AII by about 25%. A KB value of 9.01 (+/- 3.22) x 10(
      8) M was determined. At 10(-5) M, neither compounds altered the contractile
      responses to noradrenaline and KCl. In pithed rats, BIBS 39 dose dependently
      shifted the dose-response curve of AII to the right without affecting the maximal
      response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397035
TI  - Modification of chlordiazepoxide's behavioural and neurochemical effects by
      handling and plus-maze experience.
AB  - The purpose of the present experiment was to determine how a rat's prior history
      (of repeated gentle handling and/or of the elevated plus-maze apparatus) modified
      the behavioural and neurochemical response to chlordiazepoxide. In handled
      animals one previous exposure to the plus-maze rendered the rats insensitive to
      the anxiolytic effects of chlordiazepoxide in this test. This phenomenon of 'one
      trial tolerance' was not seen in unhandled rats and thus both prior handling and
      prior maze experience were necessary to abolish the behavioural response to
      chlordiazepoxide. The effects of chlordiazepoxide on K(+)-evoked [14C]GABA (gamma
      aminobutyric acid) release were also modified by the rat's past history. The drug
      induced reduction of GABA release in the cortex was abolished by prior plus-maze
      experience; whereas handling modified chlordiazepoxide's effects on GABA release
      in the hippocampus (the drug decreased release in unhandled rats and increased
      release in those given repeated gentle handling). Thus an anxiolytic response to
      chlordiazepoxide in the plus-maze was accompanied by reduced GABA release in both
      cortex and hippocampus. The 5-HT system (5-hydroxytryptamine) also proved
      sensitive to the rats' past history. The effects of chlordiazepoxide on K(+)
      evoked [3H]5-HT release from the hippocampus depended on both prior handling and
      plus-maze experience and could be predicted from the undrugged level of evoked
      release; when this was low, chlordiazepoxide increased it, when it was high,
      chlordiazepoxide reduced it. These results raise the possibility that the
      beneficial effects of a benzodiazepine may depend on the baseline condition of
      the animals.

PMID- 1397036
TI  - Quinacainol, a new antiarrhythmic with class I antiarrhythmic actions in the rat.
AB  - The antiarrhythmic and electrophysiological actions of quinacainol, a new Class I
      antiarrhythmic, were assessed in rats. Electrophysiological actions of
      quinacainol were assessed in vivo in terms of drug-induced changes in ECG,
      responses to left ventricular electrical stimulation, and changes in epicardial
      intracellular potentials to precisely characterize the electrophysiological
      effects of this putative subclass Ic antiarrhythmic compound. Antiarrhythmic
      actions were assessed in conscious rats subjected to occlusion of the LAD
      coronary artery. Antiarrhythmic actions occurred with 2.0 and 4.0 mg/kg, whereas
      8.0 mg/kg was pro-arrhythmic. At doses of 0.5 mg/kg and above quinacainol
      increased threshold currents for capture and for ventricular fibrillation. Doses
      of 2.0 mg/kg and above increased ventricular refractoriness. From 1.0 to 8.0
      mg/kg, quinacainol reduced dV/dtmax of phase 0 of epicardial action potentials
      but only 8.0 mg/kg increased action potential duration. The Q-T interval was also
      increased with the highest dose. Quinacainol dose-relatedly increased P-R
      interval whereas QRS did not change. Thus the Class I electrophysiological
      properties of quinacainol over the dose range tested did not fit accurately into
      a single subclass of the various subclasses of Class I. However, the Class Ic
      actions seen with 2.0 and 4.0 mg/kg were associated with antiarrhythmic actions.

PMID- 1397037
TI  - Effects of the putative 5-HT1A receptor antagonist NAN-190 on free feeding and on
      feeding induced by the 5-HT1A receptor agonist 8-OH-DPAT in the rat.
AB  - The effects of the putative 5-HT1A receptor antagonist NAN-190 on feeding and
      spontaneous locomotor activity in rats were examined. The drug elicited a robust,
      dose-dependent (0.01-10 mg/kg) increase in food consumption in free feeding
      animals. Microstructural analysis of feeding induced by NAN-190 (3 mg/kg)
      revealed that the drug increased the duration of feeding and number of feeding
      bouts but decreased the feeding rate. The increase in feeding induced by 3 mg/kg
      of NAN-190 was not apparent until 2-4 h after injection. This prolonged latency
      to onset of the feeding response appeared to be due to response competition.
      Thus, a 'neuroleptic-like' action of the drug on spontaneous motor activity was
      observed during the the initial 2 h following injection. A dopamine receptor
      antagonist action of NAN-190 was also indicated by the results of studies in
      which the drug was observed to block oral stereotypy induced by the dopamine
      receptor agonist apomorphine. In interaction studies, NAN-190 (0.1 and 10 mg/kg)
      failed to block the feeding response induced by the prototypical 5-HT1A receptor
      agonist 8-OH-DPAT (0.0625 and 1.0 mg/kg) and indeed, appeared to have an additive
      effect with 8-OH-DPAT on consummatory behaviour. These data suggest that NAN-190
      may act as a partial agonist rather than an antagonist at the 5-HT1A receptor and
      also provide the first evidence that the drug has dopamine receptor antagonist
      properties in vivo.

PMID- 1397038
TI  - Effects of two different reversible monoamine oxidase-A inhibitors on nociceptive
      thresholds in the rat.
AB  - The acute effect of two different reversible inhibitors of monoamine oxidase-A on
      nociceptive thresholds was evaluated in the rat by the tail-flick and hot-plate
      tests. CGP 11305-A, a monoamine oxidase-A inhibitor that also blocks serotonin
      reuptake, elicited an increase of latency in the tail-flick and the hot-plate
      test. Ineffective doses of CGP 11305-A increased nociceptive thresholds when
      administered in combination with other serotoninergic agents, i.e.
      chlorimipramine or 5-hydroxytryptophan, at doses that were ineffective alone. CGP
      22364-A, a pure inhibitor of monoamine oxidase-A, increased latency only in the
      hot-plate test. Both compounds decreased spontaneous locomotor activity at the
      doses effective in the hot-plate test, suggesting that the responses observed in
      this test are not related to a pure effect on nociceptive thresholds. The data
      suggest that the increase in serotonin availability induced by monoamine oxidase
      A inhibition alone is not sufficient to affect nociceptive thresholds.

PMID- 1397039
TI  - 13,14-Dihydro-prostaglandin E1 decreases low-density lipoprotein influx into
      rabbit aorta.
AB  - The effect of 4-week daily administration of 13,14-dihydro-prostaglandin E1
      (13,14-DH-PGE1; 2 micrograms/kg) on LDL influx into the rabbit aortic wall was
      examined versus the effect of the same dose of PGE1 and sham-treatment in 108
      male animals fed an 1% cholesterol supplemented diet. Treatment was started after
      de-endothelialization of the abdominal aorta with a Fogarty catheter. After the 1
      month treatment period the animals were injected with 10 microCi 125I-low-density
      lipoprotein (LDL; 0.5 mg protein/ml). Uptake of the radiolabelled LDL was
      measured in morphologically verified endothelialized, re-endothelialized and de
      endothelialized abdominal aortic segments. The LDL influx into the aorta was
      significantly (P less than 0.001) lower in 13,14-DH-PGE1- and PGE1-treated
      rabbits than in the controls. This reduction was most pronounced in re- and de
      endothelialized segments. No significant difference between effect of PGE1 and of
      its biologically active derivative, 13,14-DH-PGE1, on arterial LDL entry was
      found. These data demonstrate a comparable beneficial effect of 13,14-DH-PGE1 and
      PGE1 on vascular wall lipid metabolism by decreasing LDL entry into the aortic
      wall in vivo.

PMID- 1397040
TI  - AS-5370 potently antagonizes 5-HT3 receptor-mediated responses on NG108-15 cells
      and on the rat vagus.
AB  - The action of a novel 5-HT3 receptor antagonist, AS-5370, has been studied on two
      electrophysiological models for 5-HT3 receptors: whole-cell patch-clamp
      recordings from mouse neuroblastoma-rat glioma (NG108-15) cells and grease-gap
      recordings from rat isolated vagus nerve. The 5-hydroxytryptamine (5-HT)-induced
      fast inward current of voltage-clamped NG108-15 cells was antagonized by 1 nM AS
      5370 in an insurmountable manner. On the rat vagus, AS-5370 reduced the maximum
      depolarizing response to 5-HT in a concentration-dependent manner. The IC50 for
      AS-5370 on the rat vagus was 0.3-1.0 nM. The EC50 for 5-HT on the rat vagus was
      not appreciably affected by AS-5370. On the rat vagus, the (R) enantiomer of AS
      5370 was about 30 times more potent than the (S) enantiomer. The antagonist
      action of AS-5370 on these two cell types was compared with that of (+)
      tubocurarine. Unlike tubocurarine, the effect of AS-5370 on NG108-15 cells was
      not readily reversed during wash. On the rat vagus, tubocurarine antagonized in a
      competitive manner with an IC50 of 0.3-1.0 microM (pKb = 7.2). It is concluded
      that AS-5370 is a potent 5-HT3 receptor antagonist on both NG108-15 cells and the
      rat vagus, but it does not act in a competitive manner.

PMID- 1397041
TI  - Direct and indirect effects of angiotensin II on venous tone in conscious rats.
AB  - The direct and indirect effects of angiotensin II (ANGII) on mean arterial
      pressure (MAP) and mean circulatory filling pressure (MCFP), an index of body
      venous tone, were investigated in conscious rats. Dose-response curves of ANGII
      were constructed in control rats (Group I), rats pretreated with saralasin
      (competitive ANGII antagonist, Group II), with guanethidine (inhibitor of
      sympathetic postganglionic neurons. Group III), or the ganglionic blocker
      hexamethonium (Group IV) and rats given unilateral right adrenalectomy two days
      prior to the study (Group V). The infusion of single doses of ANGII in control,
      adrenalectomized, guanethidine-treated and hexamethonium-treated rats dose
      dependently increased MAP to similar maxima; ED50 value was increased by
      adrenalectomy but unaffected by guanethidine nor hexamethonium. The pressor
      effects of ANGII was almost completely abolished by saralasin. ANGII dose
      dependently increased MCFP in control rats. In hexamethonium-treated rats, ANGII
      also dose relatedly increased MCFP which reached similar maximum as that in
      control rats, but the ED50 value was reduced. Saralasin almost completely
      abolished the MCFP response. Both guanethidine and adrenalectomy reduced maximum
      MCFP response to ANGII, but neither altered the ED50 value. Our results show that
      the sympathetic nervous system contributed greater to the MCFP than MAP effects
      of ANGII. Both direct and indirect effects of ANGII are mediated via the
      activation of ANGII receptors that are susceptible to blockade by saralasin.

PMID- 1397042
TI  - Losartan potassium, a nonpeptide antagonist of angiotensin II, chronically
      administered p.o. does not readily cross the blood-brain barrier.
AB  - Recently several novel nonpeptide antagonists of angiotensin II (Ang II) have
      been identified. One of these, losartan potassium (formerly DuP 753) was
      developed as an orally active and highly selective antagonist for Ang II. As it
      is inhibited by sulfhydryl agents, it is specific for the AT1 receptor subtype.
      Since Ang II has both central and peripheral effects, we investigated whether
      losartan, given p.o. chronically, crosses the blood-brain barrier. The effects of
      chronic administration of losartan orally (p.o.) at 3 mg/kg per day for three
      days on the dipsogenic and pressor responses to a pre-established dose of Ang II
      i.v.t. (50 ng) were studied. Three series of experiments were carried out using
      conscious normotensive Sprague-Dawley rats. The rats were injected with Ang II
      intraventricularly (i.v.t.) before and after treatment of losartan p.o. and blood
      pressure and drinking responses measured. The experiments established that 3
      mg/kg losartan p.o. for 3 days antagonized pressor effects of Ang II
      intravenously (i.v.), but did not antagonize the pressor or drinking effects of
      Ang II i.v.t. Daily water intake significantly increased with chronic losartan
      p.o.. Since chronic administration of losartan p.o. was able to block the effects
      of Ang II i.v. but had no effect on Ang II i.v.t. we conclude that losartan
      potassium does not readily cross the blood-brain barrier using this dose regimen.

PMID- 1397043
TI  - Effect of SCH 37224 on anti-IgE-induced formation of sulfidopeptide leukotrienes
      in human lung parenchyma.
AB  - SCH 37224, 1-(1,2-dihydro-4-hydroxy-2-oxo-1-phenyl-1,8-naphthyridin-3-yl)
      pyrrolidinium, is a structurally novel compound that had been shown to inhibit
      leukotriene D4 formation in guinea pig lung in vitro. We tested whether SCH 37224
      is able to inhibit both the formation of eicosanoids from human lung parenchyma
      in vitro and the binding of sulfidopeptide leukotrienes to membranes of lung
      parenchyma and bronchi. SCH 37224, at a concentration of 30 and 100 microM, was
      able to inhibit antigen-induced formation of sulfidopeptide leukotrienes,
      measured as leukotriene E4, while it did not significantly affect the formation
      of prostaglandin D2. At concentrations up to 100 microM, it did not affect either
      the binding of [3H]leukotriene C4 to membranes of human lung parenchyma or human
      bronchi, or the binding of [3H]leukotriene D4 to the parenchyma. In conclusion,
      SCH 37224 is a selective inhibitor of leukotriene formation in human lung in
      vitro, which might be of potential therapeutic interest in the treatment of
      asthma.

PMID- 1397044
TI  - 8-OH-DPAT-induced inhibition of renal sympathetic nerve activity and serotonin
      neuronal firing.
AB  - The effects of the 5-HT1A receptor 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH
      DPAT) administered i.v. on medullary 5-HT neuronal firing and renal sympathetic
      nerve activity were determined in spontaneously breathing anaesthetized cats. Low
      doses of 8-OH-DPAT (1-3 micrograms/kg) caused a similar reduction in 5-HT
      neuronal firing and renal nerve activity while high doses (10-30 micrograms/kg)
      completely inhibited neuronal firing but caused only 80% inhibition of renal
      nerve activity. These data are discussed in relationship to the mechanism of
      sympatholytic action of 8-OH-DPAT and the serotonergic regulation of sympathetic
      nerve activity.

PMID- 1397045
TI  - Inhibition of locus coeruleus neurons by the phencyclidine analog, N-[1-(2
      benzo(b)thiophenyl)cyclohexyl]piperidine: evidence for potent indirect
      adrenoceptor agonist properties.
AB  - The effects of the phencyclidine derivative, N-[1-(2
      benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), on the electrical activity of
      noradrenaline (NA) neurons of the locus coeruleus (LC) were studied in halothane
      anesthetized rats. Systemic administration of BTCP potently inhibited LC neurons
      (ID50 of 1.1 +/- 0.1 mg/kg i.v.). This effect was mimicked by local microejection
      of BTCP into the LC. Both the systemic and local effects of BTCP were blocked by
      alpha 2-adrenoceptor antagonists and prevented by prior depletion of
      catecholamines with reserpine. These and other data suggest that BTCP behaves as
      a potent indirect NA agonist (i.e. via NA re-uptake and/or release systems).

PMID- 1397046
TI  - Activation of the glutamate metabotropic receptor protects retina against N
      methyl-D-aspartate toxicity.
AB  - Intraocular pretreatment with the specific metabotropic glutamate receptor
      agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in the
      adult rat reduced the excitotoxic effects induced in the retina by a single
      intraocular injection of N-methyl-D-aspartate (NMDA). Damage was estimated by
      assessing NMDA-induced loss of retinal choline acetyltransferase (ChAT) activity.
      The interaction between metabotropic and ionotropic glutamate receptors may,
      therefore, be considered an important target for in vivo pharmacological
      neuroprotection.

PMID- 1397047
TI  - Effect of SCH 23390 and quinpirole on novelty-induced grooming behaviour in
      spontaneously hypertensive rats and Wistar-Kyoto rats.
AB  - Grooming behaviour induced by exposure to a novel environment was studied in
      spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY).
      The dopamine D1 receptor antagonist, SCH 23390, and the dopamine D2 receptor
      agonist, quinpirole, were used to study brain dopamine systems in these rat
      strains, via their effects on grooming behaviour. The total grooming behaviour
      displayed in a 50-min observation period was significantly lower in SHR than in
      WKY. Except for the paw licking component no differences between the two strains
      were observed in the separate behavioural elements of grooming behaviour. SCH
      23390 and quinpirole were found to suppress novelty-induced grooming behaviour of
      both strains. In SHR, grooming behaviour was less suppressed by SCH 23390,
      whereas the suppression by quinpirole was more pronounced than in WKY. These
      results indicate that there are alterations in central dopamine systems in SHR,
      probably involving changes both in dopamine D1 and D2 receptor mechanisms in the
      brain.

PMID- 1397048
TI  - Dopamine receptor occupancy in vivo: behavioral correlates using NNC-112, NNC-687
      and NNC-756, new selective dopamine D1 receptor antagonists.
AB  - The ability of dopamine D2, mixed D1/D2 and selective D1 receptor antagonists,
      including NNC-112, NNC-687, NNC-756, to inhibit the in vivo binding of [3H]SCH
      23390 or [3H]raclopride to dopamine receptors was studied in mice and rats.
      Furthermore, the dopamine-antagonistic effects of these drugs were also studied
      in various behavioral models. Significant levels of in vivo receptor blockade
      were required for antagonism of typical dopamine agonist-mediated behaviors.
      However, fewer D1 than D2 receptors had to be blocked to produce similar
      antagonistic effects. Thus, there may be a greater receptor reserve for D2
      receptors than for D1 receptors.

PMID- 1397049
TI  - NNC-112, NNC-687 and NNC-756, new selective and highly potent dopamine D1
      receptor antagonists.
AB  - The neurochemical properties of three novel benzazepine derivatives NNC-112, NNC
      687 and NNC-756 were assessed. These compounds inhibited dopamine D1 receptor
      binding in vitro with low nanomolar to picomolar dissociation constants whereas
      those for the D2 receptor were in the micromolar range. Contrary to classical
      neuroleptics, but similar to the atypical neuroleptics, clozapine and
      fluperlapine, NNC-112, NNC-687 and NNC-756 were relatively more potent in
      inhibiting dopamine-stimulated adenylyl cyclase than [3H]SCH 23390 binding. Both
      NNC-112 and NNC-756 had high affinity for the 5-HT2 receptor whereas NNC-687 had
      low affinity for this receptor. The affinity for other receptors or
      neurotransmitter transporters was very low. In vivo, the dopamine D1 receptor
      selective profile of NNC-112, NNC-687 and NNC-756 was evident from the potent
      inhibition of D1 receptor binding whereas no effect on D2 receptor binding was
      apparent. In addition, the compounds blocked D1 receptor-mediated rotation in
      unilaterally 6-hydroxydopamine-lesioned rats, but had no effect on D2-induced
      rotation. Thus, NNC-112, NNC-687 and NNC-756 are potent and selective dopamine D1
      receptor antagonists that may be useful in the treatment of schizophrenia.

PMID- 1397050
TI  - Amitriptyline, desipramine, cyproheptadine and carbamazepine, in concentrations
      used therapeutically, reduce kainate- and N-methyl-D-aspartate-induced
      intracellular Ca2+ levels in neuronal culture.
AB  - The glutamate receptor agonists, kainate and N-methyl-D-aspartate (NMDA) result
      in the elevation of intracellular calcium levels ([Ca2+]i) in primary cultures of
      cerebellar granule neurons. Several tricyclic antidepressants (TCAs),
      amitriptyline (0.5-1 microM), desipramine (1 microM) and doxepine (1 microM)
      partially prevent this elevation induced by both of these excitatory amino acids
      (EAAs), but not elevations of [Ca2+]i induced by another EAA, quisqualate.
      Evidence suggests that this EAA-tricyclic interaction may involve voltage
      dependent Ca2+ channels since amitriptyline also partially blocks the elevation
      of [Ca2+]i induced by membrane depolarization with 40 mM KCl. However, the
      blockade is not reversed in high concentrations of extracellular Ca2+ ([Ca2+]o)
      as would be predicted by a direct interaction with Ca2+ channels. Cyproheptadine
      (0.5-1 microM), a serotonin antagonist that is structurally similar to
      amitriptyline, causes similar effects as reported above for the TCAs; however,
      ketanserine (10 microM), also a serotonin antagonist but without the tricyclic
      nucleus, is less effective in this regard. Carbamazepine, an anticonvulsant with
      a tricyclic nucleus, produces similar effects as the above three compounds only
      in higher, yet therapeutic, concentrations (50 microM). Neither 5
      hydroxytryptamine nor norepinephrine (100 microM, each) had effects on the EAA
      induced elevation of [Ca2+]i. This is the first report to show an interaction of
      tricyclic antidepressants with the function of glutamate receptors in
      concentrations which are consistent with therapeutic dosages.

PMID- 1397052
TI  - Effects of clorgyline on the release of noradrenaline from rat vas deferens.
AB  - Release of endogenous noradrenaline (NA) and functional activity of presynaptic
      alpha 2-adrenoceptors were measured in isolated rat vas deferens following acute
      (2 mg/kg) or chronic (21 * 1 mg/kg daily, i.p.) treatment with clorgyline.
      Noradrenaline tissue content was higher in rats treated chronically with
      clorgyline than in those treated acutely. In vitro experiments done in the
      presence of 1 microM desipramine and 0.5 microM yohimbine showed that NA release,
      elicited by electrical field stimulation, was higher in chronic clorgyline rats
      than in controls, while no significant difference was found between acute
      clorgyline and control rats. Yohimbine enhanced evoked release of NA in all
      treatment groups, provided that desipramine was present in the Krebs solution,
      and the enhancement was non significantly higher in chronic clorgyline than in
      acute clorgyline and control rats. Efflux of 3,4-dihydroxyphenylglycol was lower
      in chronic clorgyline rats than in other groups. No difference was found between
      the treatment groups in a 1 min [3H]NA uptake into the tissue, nor in the ability
      of desipramine (1 microM) to block the uptake. The results indicate that
      following chronic treatment with clorgyline, evoked release of NA increased, and
      there was no reduction in the ability of the presynaptic alpha 2-adrenoceptor
      inhibitory mechanism to reduce nerve stimulation induced release of NA.

PMID- 1397051
TI  - Analysis of the relaxant action of SDZ PCO 400 in airway smooth muscle from the
      ox and guinea-pig.
AB  - SDZ PCO 400 (30 nM-100 microM) suppressed the spontaneous tone of guinea-pig
      isolated trachealis. Glibenclamide (1-10 microM), phentolamine (100 microM),
      guanethidine (50 microM) and bretylium (50 microM) each antagonized SDZ PCO 400
      without antagonizing isoprenaline or theophylline. Charybdotoxin (100 nM) failed
      to antagonize SDZ PCO 400 but antagonized theophylline. The relaxant action of
      SDZ PCO 400 was ablated when spasm was induced by a K(+)-rich (120 mM) medium. In
      bovine and guinea-pig trachea, SDZ PCO 400 (10 microM) suppressed spasm evoked by
      lower (less than 40 mM) but not higher (greater than 40 mM) concentrations of
      KCl. In guinea-pig trachea the relaxant action of SDZ PCO 400 was associated with
      suppression of electrical slow waves and with marked cellular hyperpolarisation.
      SDZ PCO 400 (0.5 and 10 microM) promoted the efflux of 86Rb+ from bovine
      trachealis, an effect inhibited by glibenclamide (1 microM). It is concluded that
      the tracheal relaxant action of SDZ PCO 400 is associated with the opening of a
      plasmalemmal K(+)-channel analogous to the ATP-sensitive K(+)-channel observed in
      insulin-secreting cells.

PMID- 1397053
TI  - Characterization of the novel 5-HT3 antagonists MDL 73147EF (dolasetron mesilate)
      and MDL 74156 in NG108-15 neuroblastoma x glioma cells.
AB  - In radioligand binding experiments, MDL 73147EF and MDL 74156 inhibited the
      binding of [3H]GR65630 to 5-hydroxy-tryptamine3 (5-HT3) binding sites on
      membranes prepared from NG108-15 neuroblastoma x glioma cells. The calculated
      dissociation constants (KI) were 20.03 +/- 6.58 and 0.44 +/- 0.18 nM,
      respectively (means +/- S.E.M., n = 6 and 9, respectively). Application of 5-HT
      (10-50 microM) to voltage-clamped NG108-15 cells elicited a rapidly desensitizing
      inward membrane current, characteristic for the activation of 5-HT3 receptors.
      The 5-HT-induced membrane current was suppressed in a reversible, concentration
      dependent manner by MDL 73147EF and MDL 74156EF. The concentrations required to
      block half the 5-HT response (IC50) were 3.8 and 0.1 nM, respectively. It is
      concluded that both compounds are potent and reversible antagonists at 5-HT3
      receptors in this neuroblastoma cell line.

PMID- 1397054
TI  - Eicosanoids modulate CR1- and Fc-dependent bacterial phagocytosis.
AB  - It is known that macrophages produce large amounts of eicosanoids during
      phagocytosis and that pharmacological concentrations of prostaglandin E2 (PGE2)
      inhibit phagocytosis in several models. However, the physiological effect on
      phagocytosis of endogenous prostaglandins, produced during CR1- or FcR-mediated
      bacterial phagocytosis, remains unclear. In this study, we show that indomethacin
      inhibits the CR1- but not the FcR-dependent phagocytosis of bacteria by rat
      peritoneal cells in the same range of concentrations that inhibit the synthesis
      of PGE2, PGI2 and thromboxane A2. An exogenous supply of PGE2 and PGE1 (10(-10)
      to 10(-8) M) restored the CR1-mediated phagocytosis; higher concentrations were
      inhibitory. Our data indicate that PGE2 and/or PGI2, produced by rat peritoneal
      cells, are involved in CR1-dependent bacterial phagocytosis.

PMID- 1397055
TI  - Conversion of DNA adducts of antitumour cis-diamminedichloroplatinum(II).
      Immunochemical analysis.
AB  - Polyclonal antibodies that bind selectively to DNA modified by antitumour
      cisplatin and its analogues were isolated. The reactivity of the antibodies with
      the epitope was enhanced by thermal denaturation of DNA that had been modified by
      cisplatin before its denaturation. On the other hand, denaturation of DNA before
      its modification resulted in considerably less reaction of the antibodies. The
      conversion of monofunctional cisplatin-DNA adducts to bifunctional lesions
      increased the capability of the modified DNA to competitively inhibit the
      antibodies. The double-helical oligonucleotides containing a unique bifunctional
      adduct formed by cisplatin at the d(GG) site cross-reacted with the antibodies in
      contrast to the oligonucleotide containing a single monofunctional adduct formed
      at the d(G) site. In addition, poly(dG-dC) . poly(dG-dC) modified by cisplatin
      did not react with the antibodies. It was concluded that the antibodies
      recognized monodentate lesions, intrastrand cross-links between two purine
      nucleosides separated by one or more nucleosides and interstrand cross-links
      negligibly. The antibodies apparently recognized a chemical nature of the
      bifunctional adduct formed between two adjacent purines and not an unusual
      conformational feature of DNA resulting from the formation of this adduct. The
      antibodies were used to analyse the adducts formed by cisplatin on DNA of
      cultured cells exposed to this drug. During the subsequent incubation of the
      already exposed cells in the drug-free medium, a part of the bifunctional adducts
      of cisplatin was completely removed from DNA or transformed to the adducts not
      recognized by the antibodies.

PMID- 1397056
TI  - Characterization of ouabain high-affinity binding to rat cerebral cortex.
      Modulation by melatonin.
AB  - High-affinity [3H]ouabain binding to membrane preparations of rat cerebral cortex
      was examined using a rapid filtration procedure. At 37 degrees C, binding reached
      equilibrium in about 60 min. Scatchard analyses of the data at equilibrium
      revealed a single population of binding sites with a dissociation constant of KD
      = 3.1 +/- 0.36 nM and a binding site concentration of Bmax = 246.4 +/- 18.4
      fmol/mg protein. Kinetic analyses of the association and dissociation curves
      indicated a kinetic KD = 4.6 nM, which is in good agreement with the value
      obtained at equilibrium. When various digitalis compounds were tested for their
      ability to inhibit [3H]ouabain binding, the following Ki values (nM) were
      obtained: ouabain (3.9); digoxin (18); acetyl-digitoxin (66); k-strophanthin
      (95); digitoxin (236). When melatonin was added to the incubation medium, the
      ability of ouabain to inhibit [3H]ouabain binding increased in a dose-related
      manner to yield the following Ki values (nM): melatonin 10 nM (2); melatonin 20
      nM (1.2); melatonin 40 nM (0.8). These data suggest the existence in the rat
      cerebral cortex of high-affinity ouabain binding sites which may be a locus for
      the molecular action of melatonin.

PMID- 1397057
TI  - Effect of amphotericin B on intracellular calcium levels in cultured glomerular
      mesangial cells.
AB  - Amphotericin B induces a reduction in the glomerular filtration rate due, in
      part, to a decrease in the glomerular capillary ultrafiltration coefficient (Kf),
      possibly resulting from mesangial cell contraction. The present study has
      examined the effect of amphotericin B on intracellular free calcium
      concentrations ([Ca2+]i) in cultured glomerular mesangial cells, using the
      fluorescent probe, fura-2. Under control conditions, amphotericin B caused a
      concentration-dependent increase in [Ca2+]i with a 231 +/- 52 nM increase at a
      concentration of 10(-6) M. This increase was almost completely inhibited when
      Ca2+ ions were omitted from the cell medium (an increase of 34 +/- 7 nM, P less
      than 0.0001). Replacement of extracellular Na+ ions with N-methylglucamine caused
      a marked inhibition of the amphotericin B-induced rise in [Ca2+]i (28 +/- 5 nM, P
      less than 0.0001). Diltiazem (20 microM) also suppressed the rise in [Ca2+]i seen
      with amphotericin B (36 +/- 6 nM, P less than 0.0001). In contrast, theophylline
      (20 microM) enhanced the response to amphotericin B (351 +/- 51 nM rise, P less
      than 0.001). The results suggest that amphotericin B-induced mesangial cell
      contraction is secondary to Ca2+ entry from the extracellular space through
      voltage-dependent calcium channels. The dependence of the response on
      extracellular Na+ suggests that Na+ entry induces depolarization of the membrane
      and opening of voltage-dependent calcium channels.

PMID- 1397058
TI  - ADP-ribosylation of rho proteins is inhibited by melittin, mast cell
      degranulating peptide and compound 48/80.
AB  - The amphiphilic agents melittin, mast cell degranulating peptide and compound
      48/80 inhibit the ADP-ribosylation of the small GTP-binding proteins rho by
      Clostridium botulinum exoenzyme C3. Half-maximal and maximal inhibition (greater
      than 90%) of ADP-ribosylation occurred at about 8 and 25 micrograms/ml for
      compound 48/80, at 10 and 45 microM for mast cell degranulating peptide and at 15
      and 50 microM for melittin, respectively. In addition, these compounds increase
      the steady state GTP hydrolysis and the association and dissociation rate of GTP
      binding of rho proteins through an increase of GDP/GTP exchange. The data suggest
      that the amphiphilic agents tested interact with small GTP-binding proteins of
      the rho protein family.

PMID- 1397059
TI  - Serotonin inhibits adenylate cyclase in human platelet membranes.
AB  - Serotonin (5-HT), the non-specific 5-HT1 receptor agonist methysergide, and the 5
      HT1B receptor agonist CGS 12066 dose-dependently inhibited forskolin-stimulated
      adenylate cyclase activity in membranes derived from human platelets. Buspirone
      and ipsapirone showed partial agonist activity. The effect of 5-HT to inhibit
      forskolin-stimulated activity was partially antagonised by spiperone, yohimbine
      and pindolol, with each of these compounds showing some partial agonist activity.
      It is concluded that human platelet membranes possess receptors for 5-HT coupled
      negatively to adenylate cyclase. The relationship of these receptors to other
      binding sites which have been shown for 5-HT on platelet membranes remains to be
      finally elucidated.

PMID- 1397060
TI  - Stereoisomerism and muscarinic receptor agonists: synthesis and effects of the
      stereoisomers of 3-[5-(3-amino-1,2,4-oxadiazol)yl]-1- azabicyclo[2.2.1]heptane.
AB  - The preparation and the biological activities of the four stereoisomers of 3-[5
      (3-amino-1,2,4-oxadiazol)yl]-1-azabicyclo[2.2.1]heptane are described. The most
      potent stereoisomer, 3a, has the 3R,4R configuration, and in vitro activities in
      (pD2(% efficacy): ileum 8.8 (87%), hippocampus 9.8 (116%) and ganglion 10.2
      (36%)). 3b (3S,4S) was weaker (ileum 8.1 (121%), hippocampus 8.5 (107%), ganglion
      9.0 (63%)). The other two stereoisomers, 4a (3S,4R; ileum 7.1 (108%), hippocampus
      8.2 (116%), ganglion 7.3 (31%)) and 4b (3R,4S; ileum 7.0 (100%), hippocampus 7.0
      (120%), ganglion 7.2 (67%)) are of comparable activity, with an analogous profile
      to that of the more potent stereoisomers. Thus, compounds 3a and 4a, possessing
      the 4R stereochemistry, showed selectivity for the hippocampus over the ileum.
      Compound 3a was, however, more potent in the ganglion than in the hippocampus.
      All four stereoisomers were full agonists in the hippocampus, indicating M1
      activity; however, they were partial agonists in the depolarisation of the rat
      superior cervical ganglion, another M1-mediated response. This may be due to M2
      mediated hyperpolarization. With 3a (0.01 mg/kg i.p.), expression of c-fos mRNA
      was observed in the hypothalamus and in brain areas involved in sensory
      processing; these effects were totally blocked by pretreatment with 2 mg/kg
      scopolamine. In particular, activation of the superior colliculus is consistent
      with potent M2 activity.

PMID- 1397061
TI  - Molecular modelling of asperlicin derived cholecystokinin A receptor antagonists.
AB  - The C3-substituted benzodiazepines derived from asperlicin, e.g. devazepide (L
      364,718, MK-329), constitute the most potent class of cholecystokinin A-type
      (CCKA) receptor antagonists. In order to gain insight into the prerequisites for
      binding, we examined the conformational properties of both potent and weak
      representatives of this class with computer assisted molecular modelling (CAMM)
      techniques. The CAMM results indicate that the binding site for the C3
      substituents is a planar slot on the CCKA receptor surface and, in addition,
      allow the proposal of a model which describes the relative binding mode of the
      less potent R isomers versus that of the S isomers. The latter model illustrates
      the unique spatial properties of the benzodiazepine moiety, which we suggest
      functions primarily as an invertible core which assures an optimal arrangement of
      attached substituents.

PMID- 1397062
TI  - Discrimination between two types of P2 purinoceptors by suramin in rat
      hepatocytes.
AB  - Suramin, currently reported as a P2 purinoceptor antagonist, competitively
      inhibited P2 purinoceptor agonist-induced phospholipase C (PLC) stimulation, but
      not P2 purinoceptor agonist-induced adenylate cyclase (AC) inhibition in rat
      hepatocytes. Suramin did not inhibit vasopressin-induced PLC activity. We
      conclude that there are two types of P2 purinoceptors; one is suramin-sensitive
      and coupled to PLC in a stimulatory manner, and the other is suramin-insensitive
      and coupled to AC in an inhibitory manner.

PMID- 1397063
TI  - Adenosine A1 receptor gene structure and regulation in normotensive and
      spontaneously hypertensive rats.
AB  - In spontaneously hypertensive rats (SHR), both the response to adenosine and the
      affinity of adenosine A1 receptors (A1R) are altered. We compared the coding
      sequences and the mRNA expression levels of A1R in SHR and normotensive Wistar
      rats (NWTR). Neither the nucleotide sequence nor the mRNA level of A1R are
      altered in SHR, so that gene mutations or an altered gene regulation of A1R
      cannot account for alterations in A1R function in SHR.

PMID- 1397064
TI  - Inhibition of human liver steroid sulfotransferase activities by drugs: a novel
      mechanism of drug toxicity?
AB  - The inhibition of steroid and phenol sulfotransferase activities in human liver
      cytosol by a wide range of commonly used drugs was studied.
      Dehydroepiandrosterone (DHEA) and estrone sulfotransferase activities were
      strongly inhibited by a number of compounds, with IC50 values ranging between 440
      pM and 147 microM. For DHEA sulfotransferase, clomiphene, testosterone, danazol
      and spironolactone were the best inhibitors, with IC50 values less than 5 microM,
      whereas for estrone sulfotransferase cyclizine, ibuprofen, chlorpheniramine and
      dimenhydrinate resulted in the strongest inhibition, again with IC50 values of
      less than 5 microM. The xenobiotic substrate 1-naphthol was refractory to
      substantial inhibition, with the exception of clomiphene. The majority of the
      drugs which inhibited steroid ST activities strongly were either synthetic
      steroids, antisteroidals or were tertiary amine drugs such as tricyclic
      antidepressants and antihistamines, many of which exhibit adverse side effects
      manifesting particularly as sexual dysfunction and disruption of hormone action
      in clinical use. The importance of these findings for our understanding of the
      molecular basis of adverse drug reactions is discussed.

PMID- 1397065
TI  - Dietary iron lowers the intestinal uptake of cadmium-metallothionein in rats.
AB  - It has been shown that addition of extra calcium/phosphorus (Ca/P), zinc (Zn) and
      iron (Fe2+) to the diet results in a significant protection against cadmium (Cd)
      accumulation and toxicity in rats fed inorganic Cd salt. However, it is not clear
      whether the presence of these mineral supplements in the diet also protects
      against the Cd uptake from cadmium-metallothionein. The present study examines
      the influence of Ca/P, Zn and Fe2+ on the Cd disposition in rats fed diets
      containing either 1.5 and 8 mg Cd/kg diet as cadmium-metallothionein (CdMt) or as
      cadmium chloride (CdCl2) for 4 weeks. The feeding of Cd resulted in a dose
      dependent increase of Cd in intestine, liver and kidneys. The total Cd uptake in
      liver and kidneys after exposure to CdMt was lower than after exposure to CdCl2.
      At the low dietary Cd level and after addition of the mineral supplement, the
      kidney/liver concentration ratio increased. However, this ratio was always higher
      with CdMt than with CdCl2, suggesting a selective renal disposition of dietary
      CdMt. The uptake of Cd from CdCl2 as well as from CdMt was significantly
      decreased by the presence of a combined mineral supplement of Ca/P, Zn and Fe2+.
      The protection which could be achieved was 72 and 75% for CdMt and 85 and 92% for
      CdCl2 after doses of 1.5 mg/kg and 8 mg/kg respectively. In a following
      experiment it was shown that the protective effect of the mineral mixture against
      CdMt was mainly due to the presence of Fe2+. It seems clear that Cd speciation
      and the mineral status of the diet have a considerable impact on the extent of Cd
      uptake in rats.

PMID- 1397066
TI  - Antihypercholesterolemic effect of dipyridamole in chickens.
AB  - The administration of a 4 mg/kg dose of dipyridamole daily in chickens fed a diet
      supplemented with 2% cholesterol reversed the hypercholesterolemic effects of the
      diet. In particular, it reduced the plasma cholesterol concentration in
      approximately 18%; the levels of very-low-density lipoproteins and intermediate
      density lipoproteins and the liver cholesterol content. Although the mechanism
      was not fully elucidated, the increased excretion of cholesterol seemed to be
      responsible for the lipid lowering effect. When dipyridamole was administered in
      chickens fed the same diet without cholesterol no significant changes were
      observed. Inasmuch as the chicken lipoprotein metabolism differs in several
      aspects to human, the extrapolation of the hypocholesterolemic effect of
      dipyridamole to man must be made with care.

PMID- 1397068
TI  - DNA adducts in carp exposed to artificial diesel-2 oil slicks.
AB  - In attempts to mimic field exposure, oil slicks prepared from diesel-2 oil/water
      emulsions were poured onto the surface of water in tanks prepared fresh every day
      and liver DNA adducts were analyzed by 32P-postlabeling in carp free-swimming in
      these tanks. 'Clusters' of lipophilic DNA adducts were detected, with five major
      and numerous minor adducts. Essentially a similar adduct pattern was found in the
      liver DNA of carp exposed to crude oil-polluted water. Diesel-2 adduct induction
      was observed slowly with a steady increase to greater than 3000 amol/microgram
      DNA at day 12. After this time fish were transferred to clean water. Adduct
      levels continued to increase through day 17 (approximately 10,000 amol/microgram
      DNA) despite the cessation of exposure, but a 30% and 80% decline was evident at
      day 22 and day 27, respectively. All major adducts were distinct from the known
      benzo[a]pyrene diolepoxide-dG. These results indicate that diesel-2 oil can cause
      extensive DNA damage in carp in vivo and the damage accumulates proportionately
      with time of exposure.

PMID- 1397067
TI  - Influence of age on epithelium-dependent responsiveness of guinea-pig and rat
      tracheal smooth muscle to spasmogens.
AB  - The current study describes the influence of age and the presence of the
      epithelium on guinea-pig and rat tracheal airway smooth muscle sensitivity to the
      spasmogens histamine, acetylcholine, carbachol and potassium. In guinea-pig
      trachea from animals aged 2-52 weeks the potency of each of these spasmogens
      decreased with increased animal age. In contrast, no age-dependent changes in the
      potency of acetylcholine, carbachol or potassium were seen in rat trachea.
      Removal of the tracheal epithelium was associated with significant increases in
      the potencies of histamine and acetylcholine in guinea-pig trachea and of
      acetylcholine in rat trachea, but not of carbachol or potassium in either
      species. For histamine in guinea-pig trachea, the largest potency increase (4.6
      fold) occurred in tissue from 6-week-old animals, with the smallest increases in
      tissue from the youngest (2 weeks) and the oldest (52 weeks) animals. Thus,
      although the sensitivity of airway smooth muscle to this spasmogen fell between 2
      and 12 weeks of age, the effect of epithelial removal on sensitivity to histamine
      was apparently increased during this period. Further studies are required to
      assess the reasons for increased histamine and acetylcholine potency in airway
      smooth muscle after epithelial ablation.

PMID- 1397069
TI  - In vitro metabolism of isaxonine phosphate: formation of two metabolites, 5
      hydroxyisaxonine and 2-aminopyrimidine, and covalent binding to microsomal
      proteins.
AB  - Isaxonine phosphate or Nerfactor (2-isopropylaminopyrimidine) has been implicated
      in several cases of hepatitis which is reversible after withdrawal of the drug.
      In order to understand the cause of such hepatitis, the metabolic activation of
      isaxonine phosphate with different liver microsomes was investigated. The major
      metabolites were 5-hydroxyisopropylaminopyrimidine and 2-aminopyrimidine.
      Covalent binding to microsomal proteins was also detected. In vitro metabolic
      activation required intact microsomes, NADPH and O2 as cofactors and was
      cytochrome P-450 dependent. A sensitive fluorimetric assay of 5-hydroxyisaxonine
      was developed. The metabolism of isaxonine phosphate was compared in liver
      microsomes from rat, rabbit, dog, monkey and man and found to be qualitatively
      similar. Treatment of rats with phenobarbital increased the formation of 5
      hydroxyisaxonine, while treatment with 3-methylcholanthrene increased the
      formation of 2-aminopyrimidine but decreased that of 5-hydroxyisaxonine.
      Inhibition and reconstitution experiments demonstrated that 5-hydroxylation of
      isaxonine was catalyzed by a cytochrome P-450. Metabolic oxidation of isaxonine
      phosphate using 5-[3H]isaxonine phosphate led to a total loss of tritium in 5
      hydroxyisaxonine and partial loss of tritium in 2-aminopyrimidine and covalent
      binding to proteins.

PMID- 1397070
TI  - Routes for renal transport of methylmercury in mice.
AB  - To clarify the routes for renal methylmercury uptake, the effects of ureter
      ligation and pretreatment of probenecid, an organic anion transport inhibitor, or
      acivicin, a gamma-glutamyltranspeptidase (gamma-GTP) inhibitor, on renal
      methylmercury content were investigated in mice. For 120 min after CH3HgCl (5
      mumol/kg, i.v.) injection, renal methylmercury content in bilateral ureter
      ligated mice was approximately 50% lower than that of sham-operate mice. The
      glomerular filtration rate was reduced to about 15% of the control by ureter
      ligation. These results suggest an important role of glomerular filtration in the
      renal methylmercury uptake. Pretreatment with probenecid (0.5 or 1.0 mmol/kg,
      i.p.) reduced the renal methylmercury accumulation 30 min after CH3HgCl injection
      in a dose-dependent manner in both ureter-ligated and sham-operated mice. Urinary
      methylmercury excretion was not affected by probenecid pretreatment. Renal
      methylmercury content of ureter-ligated mice was not changed by pretreatment with
      acivicin (0.5 or 1.0 mmol/kg. i.p.), which was previously reported to decrease
      the renal methylmercury content in mice. Coadministration of GSH (10 mumol/kg,
      i.v.) with CH3HgCl increased the renal methylmercury uptake determined 5 min
      after injection in ureter-ligated mice. These results suggest that at least two
      transport systems play major roles in renal methylmercury uptake: one is a route
      from the glomeruli through the brush border membrane which is dependent on the
      action of gamma-GTP, and the other route is the one using an organic anion
      transport system through the basolateral membrane.

PMID- 1397071
TI  - Immunohistochemical localization of epidermal growth factor and its receptor
      during odontogenesis in the rat.
AB  - The expression of epidermal growth factor (EGF) and epidermal growth factor
      receptor (EGFr) in developing teeth has been immunohistochemically studied in rat
      embryos (E-16 to E-21). Both EGF and EGFr showed a similar pattern of
      distribution. A very weak immunostaining was observed in the dental germ cells
      during the bud, cap, and bell teeth stages, as well as in few ectomesenchymal
      cells. In developed, but not erupted teeth, a moderate immunoreactivity for EGF
      and EGFr was present in the odontoblasts, in the ameloblasts and in the internal
      epithelial cells, but it was stronger in the dentine. In addition, the presence
      of EGF/EGFr was also observed in the intercalated ducts of salivary glands,
      primarily the submaxillary gland, in the maxillary bone cells, and in the cells
      of the peripheral and central nervous system. These results suggest that EGF has
      little or no effect during the early periods of tooth differentiation, whereas it
      is probably involved in the production of dentine. Moreover, EGF/EGFr seem to
      participate in the maturation and differentiation of other embryonic tissues such
      as tissues of the nervous system and bone.

PMID- 1397072
TI  - Muscle response to the oral-screen activator. An EMG study of the masseter,
      buccinator, and mentalis muscles.
AB  - The myofunctional changes that occur during orthodontic treatment with functional
      appliances constructed with vestibular screen elements, such as buccal shields
      and lip pads, have not been sufficiently investigated. The aim of this study was
      to examine electromyographically the response of the masseter, buccinator and
      mentalis muscles to the oral-screen activator (OSAC), which is a conventional
      activator constructed with buccal shields and lip pads. The material consisted of
      10 children, with Angle Class II, division 1 malocclusion and narrow dental
      arches (mean age 10.7 years), treated at the Department of Orthodontics, School
      of Dentistry, Malmo, Sweden. The group had a mean overjet of 8.5 mm, and a mean
      ANB angle of 6 degrees. Six out of the 10 cases had incompetent lips at relaxed
      lip position. The construction bite of the OSAC was taken with the anterior teeth
      in edge-to-edge position. The recording procedure included the following
      positions: (a) postural position of the mandible with lips relaxed and lips
      closed; (b) clenching; (c) swallowing saliva; and (d) spatula exercise. EMG
      recordings were made after 1, 2, and 3 months of appliance treatment. Differences
      between means were tested with a two-way analysis of variance (ANOVA). The
      results showed that during postural position with lips closed there was a
      statistically significant increase in mentalis EMG with the oral-screen activator
      in place. The buccinator and masseter muscles showed no EMG activity during rest
      with or without the appliance in the mouth. During clenching we found no
      statistically significant difference in masseter EMG with or without the
      appliance in place. During swallowing saliva a statistically significant decrease
      was recorded in mentalis EMG with the oral-screen activator in the mouth, while
      buccinator activities remained the same with and without the appliance. The
      masseter activity, on the other hand, increased significantly with the activator
      in place. During spatula exercise mentalis and buccinator were highly activated.
      The conclusions drawn from this study are that the oral screen activator (OSAC)
      increased masseter activity during swallowing, but it remained unchanged during
      clenching. Lip pads increase mentalis activity during lip closure, but reduce
      mentalis hyperactivity during swallowing. The buccinator activity was
      insignificant and buccal shields did not change that activity. Spatula exercise
      stimulates both mentalis and buccinator activity.

PMID- 1397073
TI  - Perception of malocclusion in 11-year-old children: a comparison between personal
      and parental awareness.
AB  - In orthodontic counselling an understanding of how individuals perceive their
      occlusal features is important to ensure effective communication and for
      provision of adequate advice on treatment need. The purpose of the present study
      was to assess personal and parental awareness of malocclusion in children, and to
      examine whether agreement existed between children and their parents on
      assessments of malocclusion traits. Of 104 randomly selected fourth-grade
      children 99 presented themselves at a public dental clinic. Ninety-three
      accompanying parents attended. Awareness was assessed by comparing the opinion of
      parents and children on the presence or absence of anterior malocclusion with
      direct measurements on dental study casts. The subjects' abilities to identify a
      polaroid of the child's dentition in a panel of 17 alternative photographs were
      also used as a measure of awareness. The findings revealed a moderate level of
      awareness among both the children and their parents. About half of the children
      and the parents identified the child's photograph on the first attempt. About
      three-quarters of the traits recorded as marked/severe malocclusion and about
      half of the mild/moderate traits were recognized. A significant association
      existed between the number of correct reports on traits given by the children and
      the parents. However, agreement across professional, child, and parental
      assessments varied for the different traits. The results indicated that the
      individual's comprehension of professional terms may be unclear and that
      professionally defined cut-off points often do not coincide with norms existing
      within the actual family unit.

PMID- 1397074
TI  - Need and demand for orthodontic treatment in an adult Swedish population.
AB  - The prevalence of malocclusion, the need for and the demand for orthodontic
      treatment was studied in a randomly selected adult Swedish population > or = 20
      years of age. Nine-hundred-and-twenty subjects were examined of whom 669 had
      their own teeth in occlusion. From those a group of 157 subjects was selected on
      the basis of objective need and/or subjective demand for orthodontic treatment.
      The various regimens of treatment required in this group were investigated. The
      prevalence of malocclusion ranged from 17 to 53 per cent in the various age
      groups. The spectrum of malocclusion was similar to that previously reported in
      Swedish children. The awareness of their malocclusion was higher among younger
      than older subjects and among those who had severe malocclusion. Objective
      treatment need, evaluated by two experienced orthodontists, was estimated at 11
      per cent of the total population, whilst orthodontic treatment was requested by
      approximately 5 per cent of the population studied.

PMID- 1397075
TI  - Ectopic eruption of maxillary first permanent molars and association with other
      tooth and developmental disturbances.
AB  - The associations between tooth and eruption disturbances in four groups of
      children selected primarily with only one diagnosed eruption or developmental
      disturbance in each group was analysed. Ninety-two children were primarily
      diagnosed with ectopic eruption of maxillary first permanent molars, 93 children
      with infra-occlusion and ankylosis of primary molars, 91 children with ectopic
      eruption of maxillary canines, and 97 children with aplasia of premolars. Of the
      children studied 69-79 per cent had only a single one of the four disturbances
      studied. In 18-28 per cent there was one additional disturbance and in 2-3 per
      cent two additional disturbances. From chi square contingency tests, it was found
      that infra-occlusion of primary molars and aplasia of premolars exhibited a
      higher prevalence in both directions compared to the expected population
      prevalence. Ectopic eruption of maxillary canines showed a significantly higher
      prevalence than expected in all the other three groups. Our interpretation is
      that these results support the hypothesis of a common, presumably hereditary,
      aetiology. Thus, the four conditions studied would be different manifestations of
      one syndrome, each manifestation having an incomplete penetrance. With closer
      follow-up of the maxillary canines during the eruption period in children with
      some of the other three disturbances, prophylactic, or early interceptive
      measures may be taken and complicated orthodontic treatment be reduced or
      avoided.

PMID- 1397076
TI  - Nuclear bodies (NBs): a newly "rediscovered" organelle.
AB  - Nuclear bodies (NBs) were first described in detail some 30 years ago, by
      conventional electron microscopy, as prominent interchromatin structures found
      primarily in the nuclei of malignant or hyperstimulated animal cells. Subsequent
      studies have shown that NBs are ubiquitous organelles, but they are numerically
      and morphologically quite varied. With the recent discovery of human
      autoantibodies against several key nuclear antigens present in some NBs, these
      structures are once again the subject of much attention. At least one class of
      NBs, coiled bodies, has been shown to be nucleolus-derived and to contain not
      only nucleolus-associated antigens, but also many of the snRNP components
      involved in pre-mRNA splicing. These data suggest that coiled bodies, and perhaps
      other NBs as well, are multifunctional and may be involved in the processing or
      transport of both pre-mRNA and pre-rRNA. Further evidence is provided showing
      that NBs constitute distinct nuclear domains whose functional significance is
      just now emerging.

PMID- 1397077
TI  - Reactivation of DNA replication in erythrocyte nuclei by Xenopus egg extract
      involves energy-dependent chromatin decondensation and changes in histone
      phosphorylation.
AB  - Reactivation of chicken erythrocyte nuclei for DNA replication in Xenopus egg
      extracts involves two phases of chromatin remodelling: a fast decondensation
      leading to a small volume increase and chromatin dispersion occurring within a
      few minutes (termed stage I decondensation), followed by a slower membrane
      dependent decondensation and enlargement of up to 40-fold from the initial volume
      (stage II decondensation). Chromatin decondensation as measured by nuclear
      swelling and micrococcal nuclease digestion required ATP. We observed a
      characteristic change in the phosphorylation pattern of erythrocyte proteins upon
      incubation in egg extract. While histones H5, H2A, and H4 became selectively
      phosphorylated during decondensation, the phosphorylation of histone H3 and of
      several nonhistone proteins was prevented. Furthermore, histone H5 was
      selectively released from erythrocyte nuclei in an energy-dependent reaction.
      These molecular changes already occurred during stage I decondensation and they
      persisted during stage II decondensation. DNA replication was confined to nuclei
      of stage II decondensation which incorporated lamin LIII from the egg extract.
      These results show that initiation of DNA replication in chicken erythrocytes
      requires in addition to ATP-dependent chromatin remodelling (stage I), further
      changes in chromatin structure that correlates with lamin LIII incorporation, and
      stage II decondensation.

PMID- 1397078
TI  - Splicing thermotolerance maintains Pre-mRNA transcripts in the splicing pathway
      during severe heat shock.
AB  - Thermotolerance, the ability of cells and organisms to withstand severe elevated
      temperatures after brief exposure to mild elevated temperatures, has been studied
      in numerous laboratories. Survival thermotolerance is defined as the increase in
      cell or organism survival at severe elevated temperatures after a pretreatment at
      mild elevated temperatures. This study examines splicing thermotolerance in
      Drosophila melanogaster, the ability to splice pre-mRNAs made at the severe
      temperature (38 degrees C) after a brief pretreatment at a milder temperature (35
      degrees C). It is probably one of a number of mechanisms by which cells adapt to
      heat shock. These experiments demonstrate that pre-mRNAs synthesized at the
      severe temperatures in splicing thermotolerant cells, although protected in
      splicing-competent complexes, are not actually processed to mature mRNAs until
      the cells are returned to their normal temperature. We have also studied the
      kinetics of acquisition and loss of splicing thermotolerance. As little as 10 min
      of pretreatment at 35 degrees C was sufficient to provide full splicing
      thermotolerance to a 30-min severe heat shock of 38 degrees C. Pretreatments of
      less than 10 min provide partial splicing thermotolerance for a 30-min severe
      heat shock. Full splicing thermotolerance activity begins to decay about 4 h
      after the cessation of the 35 degrees C incubation and is completely lost by 8 h
      after the pretreatment. The kinetics experiments of pre-mRNAs synthesized during
      the 38 degrees C treatment in splicing thermotolerant cells indicate that one or
      more splicing thermotolerance factors are synthesized during the 35 degrees C
      pretreatment which interact with pre-mRNA-containing complexes to keep them in a
      splicing-competent state. These kinetic experiments also indicate that in cells
      which are partially splicing thermotolerant, the pre-mRNAs synthesized early
      during the 38 degrees C incubation are protected, whereas those synthesized late
      are not. In the absence of splicing thermotolerant factors, the pre-mRNA
      containing complexes leave the normal splicing pathway and are allowed to exit to
      the cytoplasm.

PMID- 1397079
TI  - Heat shock-induced redistribution of a 160-kDa nuclear matrix protein.
AB  - In this paper we describe a 160-kDa protein (p160) which is present in the
      nuclear matrix of rat, mouse, and human cells. Biochemical and ultrastructural
      analysis shows that p160 is associated with the internal matrix and is not
      present in the lamina-pore complex. Immunoelectron microscopy shows that the
      protein is part of the extranucleolar, fibrogranular network of the nuclear
      matrix. During an in vivo 42 degrees C heat treatment of HeLa cells, A431 human
      epidermoid cells, and T24 human bladder carcinoma cells, p160 transiently formed
      large clusters inside the nucleus. These p160 clusters are associated with the
      nuclear matrix network, as judged by immunolabeling on isolated nuclear matrices.
      The percentage of cells showing p160 clusters increased proportionally with
      longer heat treatments, reaching a maximum after a period of 3 h. At this time 70
      +/- 5% of the cells displayed these clusters. Clustering decreased after longer
      heat treatments and the anti-p160 staining pattern became diffuse granular again.
      Other nuclear components, such as the A1 antigen of hnRNP (ribonucleoprotein),
      the Sm antigen of snRNPs, and lamins A and C, did not cluster during the 42
      degrees C treatment, indicating that this reallocation is characteristic for the
      p160 matrix protein. These results demonstrate that p160 is an internal nuclear
      matrix element with a dynamic spatial distribution.

PMID- 1397080
TI  - Temporal and spatial differences in glycosaminoglycan synthesis by fetal lung
      fibroblasts.
AB  - In studies of the ontogeny of fibroblast-epithelial interactions during late
      fetal lung rat lung development, we have identified two subpopulations of
      fibroblasts which differed in their ability to promote epithelial cell
      proliferation or differentiation. As glycosaminoglycans (GAGs) have been
      implicated in the regulation of these processes we have tested whether the two
      fibroblast populations synthesize different GAGs and whether the GAG pattern
      changes with development. Fibroblasts incorporate more [3H]glucosamine and Na2
      35SO4 into GAGs than epithelial cells. Both cell types deposited a significant
      amount of newly synthesized GAGs in the cell-matrix layer. GAGs were lost faster
      from the cell-matrix layer of fibroblasts (t1/2 = 12 h) than from that of
      epithelial cells (t1/2 = 48 h). Total GAG synthesis by fibroblasts did not change
      with advancing gestation, but synthesis of sulfated GAGs by epithelial cells
      declined with advancing gestation. Independent of gestational age epithelial
      cells synthesized predominantly heparan sulfate. Depending on their proximity to
      the epithelium, fibroblasts differed in their production of GAGs. Fibroblasts in
      close proximity to the epithelium mainly produced and secreted hyaluronan. More
      distant fibroblasts, from the pseudoglandular stage of lung development
      synthesized primarily heparan sulfate and chondroitin sulfate. This same
      population of fibroblasts from the canalicular stage of lung development,
      produced more hyaluronan. As the shift to hyaluronan occurs with the thinning of
      the alveolar septal wall, this finding suggests that developmentally regulated
      GAG production by fibroblasts may facilitate epithelial-fibroblast interaction,
      thus influencing fetal lung growth and differentiation.

PMID- 1397081
TI  - Deletions in the regulatory or kinase domains of protein kinase C-alpha cause
      association with the cell nucleus.
AB  - We have constructed expression plasmids carrying protein kinase C (PKC) cDNAs
      with deletions in the coding region. Two truncated molecules, consisting only of
      the kinase domain of PKC-alpha, were generated by removing parts of the cDNA
      coding for the regulatory region. Another mutant molecule was created by deleting
      95 amino acids from the C-terminal part of the molecule. The full-length cDNA
      coding for PKC-alpha and its deletion constructs was expressed in COS cells.
      Using cell fractionation experiments and immunofluorescence staining, we
      demonstrate here that in contrast to the cytosolic localization of full-length
      PKC-alpha, the truncated forms, coding only for the kinase domain, were found
      exclusively in the cell nucleus. Further subfractionation of nuclei isolated from
      these transfected cells indicated partial association with the nuclear envelopes.
      Expression of the cDNA lacking the C-terminal part of the molecule in COS cells
      encoded a truncated molecule that was found both in the cytosol and in the
      nucleus. We also show that translocation of full-length PKC-alpha molecules to
      the cell nucleus occurred in response to phorbol ester treatment. Thus, it
      appears that accumulation of PKC-alpha in the nucleus results either by phorbol
      ester activation or by deletions of specific regions of the molecule. A molecular
      mechanism for the nuclear translocation of phorbol ester-activated PKC-alpha or
      its truncated molecules is suggested.

PMID- 1397082
TI  - The attachment of nematocytes from the primitive invertebrate Hydra to
      fibronectin is specific and RGD-dependent.
AB  - The transient attachment of cells to components of the extracellular matrix is an
      important step in the complex molecular mechanisms involved in amoeboid cell
      locomotion. We have analyzed the attachment of nematocytes from the freshwater
      cnidarian Hydra to fibronectin which is a constituent of the mesoglea, the
      extracellular matrix, of the polyps. The percentage of attaching cells increased
      gradually in a concentration-dependent manner and reached a plateau value at a
      fibronectin concentration of 50 micrograms/ml. Attachment was inhibited by
      exposure of the fibronectin-coated surfaces to antibodies against the cell
      binding domain of fibronectin or by incubating the cells with peptides containing
      the recognition sequence Arg-Gly-Asp (RGD) known from vertebrate cells. This,
      together with data obtained by affinity chromatography, indicates that RGD
      dependent binding to fibronectin, mediated by a receptor which possibly belongs
      to the integrin family, already occurs in Hydra, a member of an evolutionary low
      invertebrate phylum.

PMID- 1397083
TI  - Expression of the calcium binding protein calretinin in WiDr cells and its
      correlation to their cell cycle.
AB  - Ca2+ ions intervene during different phases of the progression of the cell cycle,
      but only one calcium-binding protein, calmodulin, has been shown to be associated
      with dividing cells. We therefore screened cancer cells for the presence of other
      related calcium-binding proteins. Using molecular biological and
      immunohistochemical techniques we show that human tumor cells of epithelial
      origin, express calretinin. Calretinin immunoreactivity can be demonstrated at
      precise moments of the cell cycle and, in particular, in phase G1 and during
      mitosis. During mitosis calretinin is localized both in the cytoplasm and in the
      mitotic spindle. In the cytoplasm we find calretinin after prophase and until
      telophase. In the spindle apparatus, calretinin is already present in cells in
      prometaphase and persists in all the succeeding mitotic phases. It is associated
      with the kinetochore microtubules but, in contrast to calmodulin, also with the
      polar microtubules. The role that calretinin plays in well-defined moments of the
      cell cycle of these cells is as yet unknown, but our results strongly suggest
      that, in collaboration with other molecules, calretinin intervenes in the dynamic
      phenomena regulating the separation of the chromosomes.

PMID- 1397084
TI  - Cytochalasans and PMA induce IL-2 receptors on CD8+ lymphocytes.
AB  - The cytochalasans, fungal metabolites that interact with actin, can affect
      lymphocyte proliferation; high concentrations inhibit lectin-induced
      proliferation and low concentrations augment it. The phorbol ester tumor
      promoter, PMA, alone is not mitogenic for primary lymphocytes but enhances the
      activity of mitogenic lectins. Because the cytochalasans have been reported to
      increase intracellular Ca2+ and because PMA activates protein kinase C,
      lymphocytes were treated with PMA and cytochalasin B (CyB) to determine if this
      combination would induce DNA synthesis. While this treatment by itself did not
      cause proliferation, lymphocytes cultured with PMA and CyB overnight, washed, and
      recultured with IL-2 proliferated to the same degree as lymphocytes stimulated
      with Con A. Three different cytochalasans, cytochalasin B, cytochalasin D, and
      chaetoglobosin C, all of which bind to cellular actin with different affinities
      and only one of which affects glucose transport, induced IL-2 receptors in
      combination with PMA. Flow cytometric analysis with an antibody to the IL-2
      receptor alpha subunit confirmed the induction of receptors on CD8+ cells.
      However, no IL-2 was produced after the exposure of lymphocytes to the
      combination of cytochalasans and PMA. Therefore, there was sufficient signal to
      induce IL-2 receptor expression but not to induce IL-2.

PMID- 1397085
TI  - Effects of TGF beta 1 on the proliferation and differentiation of an immortalized
      astrocyte cell line: relationship with extracellular matrix.
AB  - The astrocyte cell line (C.LT.T.1.1.), which is immortalized and has retained a
      normal density-dependent regulation of growth, is a suitable model for studying
      the relationships between proliferation, differentiation, and the production of
      extracellular matrix. The growth factor TGF beta 1 was used to modulate these
      processes. When added to proliferative cells, it inhibited growth and caused
      morphological changes. It also suppressed the growth arrest at confluence, so
      that the cells formed multilayers of parallel spindle-shaped cells. Whereas
      untreated control cells expressed progressively the glial fibrillary acidic
      protein (GFAP) after arrest of multiplication, the addition of TGF beta 1 to
      proliferative cells prevented GFAP expression and accumulation of its mRNA.
      Concomitantly, it increased the amounts of laminin, fibronectin, and collagens
      synthesized during the growth phase and greatly altered the composition and the
      structure of the matrix deposited at confluence. In contrast, when added after
      cell differentiation had begun, TGF beta 1 did not alter the appearance of the
      matrix whereas it still stimulated, but to a lesser extent, extracellular matrix
      components production. The results show that TGF beta 1 prevents the transition
      from the proliferating to the differentiating state and correlatively alters the
      composition and structure of the extracellular matrix.

PMID- 1397086
TI  - Transferrin-receptor-independent but iron-dependent proliferation of variant
      Chinese hamster ovary cells.
AB  - The purpose of this study is to clarify the role of iron, transferrin, an iron
      binding protein in vertebrate plasma, and transferrin receptors in cell
      proliferation. Transferrin, which is indispensable for most cells growing in
      tissue culture, is frequently referred to as a "growth factor". Proliferating
      cells express high numbers of transferrin receptors, and the binding of
      transferrin to their receptors that is needed for cells to initiate and maintain
      their DNA synthesis is sometimes regarded as analogous to other growth factor
      receptor interactions. Although numerous previous experiments strongly indicate
      that the only function of transferrin in supporting cell proliferation is
      supplying cells with iron, they did not completely rule out some direct or
      signaling role transferrin receptors could play in cell proliferation. To address
      this issue, we exploited transferrin-receptor-deficient mutant Chinese hamster
      ovary (CHO) cells (McGraw, T. E., Greenfield, L., and Maxfield, F. R., 1987, J.
      Cell. Biol. 105, 207-214) in which various aspects of iron and transferrin
      metabolism in relation to their capacity to proliferate were investigated.
      Variant cells neither specifically bind transferrin nor do their extracts contain
      any detectable functional transferrin receptors, yet they proliferate and
      synthesize DNA with rates comparable to those observed with parent CHO cells.
      Desferrioxamine, an iron chelating agent, inhibits growth and DNA synthesis of
      both variant and control CHO cells. This inhibition can be fully alleviated, in
      both cell types, by ferric pyridoxal isonicotinoyl hydrazone, which can supply
      cells with a utilizable form of iron by a pathway not requiring transferrin and
      their receptors. Studies of 59Fe uptake and 125I-transferrin binding revealed
      that parent cells can take up iron by at least three mechanisms: from transferrin
      by receptor-dependent and -independent (nonspecific, nonsaturable, not requiring
      acidification) pathways and from inorganic iron salts (initially present in the
      medium as FeSO4). Although variant CHO cells are unable to acquire transferrin
      iron via the receptor pathway, two remaining mechanisms provide these cells with
      sufficient amounts of iron for DNA synthesis and cell proliferation. In
      conclusion, although transferrin receptors are dispensable in terms of their
      absolute requirement for proliferating cells, a supply of iron is still needed
      for their DNA synthesis. Transferrin-receptor-deficient CHO cells may be a useful
      model for investigating receptor-independent iron uptake from transferrin and
      nontransferrin iron sources.

PMID- 1397087
TI  - Phosphorylation of a 225-kDa centrosomal component in mitotic CHO cells and sea
      urchin eggs.
AB  - Components of centrosomes are those among cellular proteins that are
      phosphorylated at the transition from interphase to mitosis. Using an anti
      phosphoprotein antibody (CHO3) directed against isolated mitotic CHO spindles, we
      identified a 225-kDa centrosomal phosphocomponent in mitotic CHO cells and in
      cleaving sea urchin eggs. The 225-kDa protein is tightly attached to the
      centrosome, which allowed us to separate it from other spindle-associated factors
      by high salt extraction. Phosphorylation of the 225-kDa protein occurred during
      mitosis. This was shown by isotope labeling on gels as well as by visualization
      of thiophosphorylated centrosomes with an anti-thiophosphoprotein antibody (M.
      Cyert, T. Scherson, and M. W. Kirschner, 1988, Dev. Biol. 129, 209) after
      preincubation with ATP-gamma-S in vivo and in vitro. Mitotic spindles isolated
      from CHO cells retained their ability to phosphorylate the centrosomal component,
      whereas sea urchin spindles did not, possibly due to loss or inactivation of
      protein kinase(s) during spindle isolation. The enzyme associated with isolated
      CHO spindles was extractable by high salt treatment and was capable of
      phosphorylating many spindle components, including the 225-kDa centrosomal
      protein of CHO cells and sea urchin embryos. Such high salt extracts contain
      protein kinases, including cell cycle control protein kinase p34cdc2, suggesting
      that the enzyme responsible for centrosomal phosphorylation could be p34cdc2 or
      other downstream mitotic kinases activated by the action of p34cdc2.

PMID- 1397088
TI  - Differential regulation of thyroid cell-cell and cell-substrate adhesion by
      thyrotropin.
AB  - Preservation of cell aggregation is necessary for thyroid follicular
      differentiation in vitro and requires stimulation by thyrotropin (TSH). We have
      tested the hypothesis that TSH preferentially increases thyroid cell-cell
      adhesion relative to cell-substrate adhesion. Cell-cell adhesion was measured in
      short-term suspension cultures by the decrease in the fraction of single cells
      remaining in culture (free cell ratio, FCR). When incubated in medium alone
      freshly isolated cells showed a progressive fall in FCR but this was accelerated
      by TSH and the cyclic AMP analog, 8-(4-chlorophenylthio)cyclic AMP. Aggregation
      was dependent upon extracellular Ca2+ and also promoted by a cell-free membrane
      extract. In contrast, attachment of cells to plastic dishes treated for tissue
      culture was not affected by TSH. We conclude that thyroid cells possess a TSH
      sensitive cell adhesion system. The preferential increase in cell-cell adhesion
      may be one mechanism by which TSH stimulates the formation and preservation of
      follicles in vitro.

PMID- 1397089
TI  - Reduced tyrosine phosphorylation in polyamine-starved cells.
AB  - Onset of cell proliferation is associated with enhanced turnover of the
      polyamines putrescine, spermidine, and spermine, particularly evident in the
      massive increase in the activity of the rate-limiting enzyme in their production,
      ornithine decarboxylase (ODC). The physiological functions of these polyamines,
      however, have remained unclear. Here we report that treatment of LSTRA cells for
      2-18 h with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of
      ODC, decreased the amount of phosphotyrosine in several cellular substrates
      including the T cell protein tyrosine kinase p56lck. No reductions in the amount
      of p56lck, overall synthesis of protein and DNA, or cell viability were observed
      until much later. DFMO did not affect the catalytic activity of p56lck in vitro
      and the activity of p56lck immunoprecipitated from DFMO-treated cells was
      unaltered. Addition of putrescine, the reaction product of ODC, completely
      reversed the effect of DFMO on tyrosine phosphorylation. Finally, we provide
      evidence that polyamines reduce the activity of cellular protein tyrosine
      phosphatases toward endogenous substrates. Our results suggest that polyamines
      may influence the extent of tyrosine phosphorylation during cell proliferation
      and malignant transformation, perhaps by modulating the rate of dephosphorylation
      of specific target proteins.

PMID- 1397090
TI  - Hydrogen peroxide lethality is associated with a decreased ability to maintain
      positive DNA supercoiling.
AB  - Hydrogen peroxide is more toxic to mammalian cells at 37 degrees C than 0 degree
      C at all concentrations studied. Histone-free nuclei (nucleoids) extracted from
      treated cells have a reduced ability to maintain positive DNA supercoiling, with
      the maximum effect at the higher temperature. Prior exposure of cells to sodium
      ascorbate at 0 degree C increased both toxicity and the inhibition of nuclear
      supercoil rewinding. After exposure at 0 degrees C, normal levels of supercoiling
      returned with both a fast and a slow component, kinetics characteristic of DNA
      single-strand break repair; the fast component was eliminated when cells were
      exposed at 37 degrees C due to in situ rejoining. At least a portion of the
      lethal lesions induced by hydrogen peroxide are DNA double-strand breaks (dsb)
      because the dsb repair-deficient mutant, xrs-5, is approximately two to three
      times more sensitive than wild-type cells over the initial portion of the
      survival curve. However, the increased toxicity found after exposure at 37
      degrees C is observed equally in both cell lines, indicating that temperature
      dependent cell killing is not directly linked to DNA dsb. It is suggested that
      cell killing at 37 degrees C is mediated through two linked processes. First,
      hydrogen peroxide may disrupt cation-stabilized nuclear supercoiling by direct
      ion oxidation. Second, as a part of the oxidation process, hydrogen peroxide will
      produce potentially cytotoxic free radicals close to the DNA-linked metal site,
      limited in extent only by the presence of chemicals capable of reducing metal
      ions prior to reoxidation.

PMID- 1397092
TI  - Inhibition of cell adhesion to plastic substratum by phosphorothioate
      oligonucleotide.
AB  - Antisense oligonucleotides have been widely used to achieve specific inhibition
      of targeted gene expression. However, the mechanism of action is not well
      understood and in many systems sequence-independent effects occur. We have
      recently shown that chronic administration of an antisense c-myc phosphorothioate
      oligonucleotide can specifically inhibit expression of the c-myc protein and
      growth in human breast cancer cells. We now identify an additional effect of the
      same oligonucleotide on cell adhesion. Transient delivery through electroporation
      of 2.5 microM antisense-myc oligonucleotide to MCF-7 cells results in 85%
      inhibition of adhesion to plastic substratum within 24 h. Both the onset of this
      effect and the subsequent recovery occur without a change in cell viability,
      growth, or alteration of adhesion to Matrigel, collagen IV, laminin, or
      fibronectin. However, no parallel changes in c-myc mRNA or protein expression are
      detectable, suggesting that in this instance inhibition of adhesion caused by
      antisense-myc oligonucleotide may involve a mechanism independent of the target
      sequence.

PMID- 1397091
TI  - Stimulation of DNA synthesis in senescent human cells following incubation with
      plasma membranes.
AB  - DNA synthesis and mitosis were increased in mitogen-stimulated senescent WI-38
      cells following incubation with plasma membranes prepared from young or senescent
      WI-38 cells, A431 cells, 3T3 cells, or NR6 cells. The percentage of [3H]thymidine
      labeled nuclei in senescent cultures was two- to fivefold greater than that seen
      in controls in which cells were incubated in the absence of membranes or in the
      presence of boiled membranes. The effect was trypsin sensitive, suggesting that a
      protein moiety is necessary for stimulation of DNA synthesis. As the culture age
      increased, basal levels of DNA synthesis, as well as maximal stimulation of DNA
      synthesis following incubation with plasma membranes, decreased. These
      observations are consistent with the hypothesis that different subpopulations
      exist in senescing cultures and suggest a complex pattern of inhibitory and
      stimulatory regulation of cell proliferation.

PMID- 1397093
TI  - Intracellular localization of terminal transferase during the cell cycle.
AB  - Changes in the localization of terminal transferase during the cell cycle in
      random cultures of human pre-T leukemia line RPMI-8402 were examined by light and
      electron microscopy on immunoperoxidase-stained preparations. Paraformaldehyde
      fixed and saponin-permeabilized human cells were used with a monoclonal anti
      human terminal deoxynucleotidyl transferase (TdT) primary reagent to demonstrate
      changes in enzyme distribution occurring between interphase and mitosis. Nuclear
      localization is found uniformly during interphase. At metaphase, however, the
      majority of TdT staining appears randomly distributed in the cytoplasm and traces
      of TdT staining remain associated with mitotic chromatin. At later phases, when
      the daughter cells are forming, the enzyme again appears to be restricted to the
      new nuclear structure.

PMID- 1397095
TI  - Membrane aging during cell growth ascertained by Laurdan generalized
      polarization.
AB  - The sensitivity of the fluorescent probe Laurdan to the phase state of lipids has
      been utilized to detect modifications in the composition and physical state of
      cell membranes during cell growth. In phospholipid vesicles, the Laurdan emission
      spectrum shows a 50-nm red shift by passing from the gel to the liquid
      crystalline phase. The Generalized Polarization (GP) value has been used for the
      data treatment instead of the ratiometric method common in investigations
      utilizing other fluorescent probes that display spectral sensitivity to medium
      properties. The GP value can be measured easily and quickly and possesses all the
      properties of "classical" polarization, including the additivity rule. Once
      Laurdan limiting GP values have been established for the gel and the liquid
      crystalline phase of lipids, the quantitative determination of coexisting phases
      in natural samples is possible. In the present work the observation of a relevant
      decrease in the fractional intensity of the liquid-crystalline phase in K562 cell
      membranes during 5 days of asynchronous growth is reported. A decrease in the
      "fluidity" of cell membranes in K562 cells kept in culture for several months is
      also reported. The procedure developed for labeling cell membranes with Laurdan
      is reported and the influence of cell metabolism on fluorescence parameters is
      discussed. Also discussed is the influence of cholesterol on Laurdan GP.

PMID- 1397094
TI  - Stimulation by GH of IGF1 proforms synthesized by rabbit chondrocytes cultured
      with bFGF in serum-free medium.
AB  - The IR-IGF1 production by rabbit epiphyseal chondrocytes cultured in serum-free
      medium was analyzed. Cell proliferation was induced by the addition of 10 ng/ml
      basic fibroblast growth factor (bFGF) without or with 100 ng/ml recombinant human
      growth hormone (hGH). GH alone induced no cell multiplication. Chondrocytes
      treated with bFGF alone secreted an IR-IGF1 activity proportional to the mitotic
      activity of the cells. A specific positive IGF1 immunostaining was localized in
      the Golgi of control and hGH-treated cells. The IR-IGF1 activity recovered into
      culture medium was mainly composed of three fractions of apparent MW 6-8 kDa, 9
      14 kDa, and 16-18 kDa. [35S]Methionine pulse-chase experiments indicated that the
      radiolabeled 16-18 kDa IR-IGF1 fraction was partly converted into the 9-14 kDa
      and 6-8 kDa fractions. At equilibrium, 70% of the chondrocyte IR-IGF1 activity
      was recovered as 9- to 18-kDa forms which contained high IR-proIGF1A activity.
      The 6-8 kDa fraction had biochemical characteristics similar to those of the
      mature IGF1 peptide. Similar results were observed when 4% fetal calf serum was
      added to the culture. The addition of 100 ng/ml of hGH significantly and
      specifically increased IGF1 precursor material, which thus represented 90% of
      total IR-IGF1 activity. On Day 16 of the culture, when cells stopped dividing,
      the amount of chondrocyte IR-IGF1 was significantly lower than during cell
      proliferation, and hGH had no effect on this production. These data indicate that
      cultured chondrocytes produce more IGF1 precursors than mature IGF1 and that GH
      specifically stimulates biosynthesis of IGF1 precursors but not IGF1 per se. A GH
      dependent biological function of IGF1 proforms in chondrocytes remains to be
      demonstrated.

PMID- 1397096
TI  - Bradykinin and muscarine induce Ca(2+)-dependent oscillations of membrane
      potential in rat glioma cells indicating a rhythmic Ca2+ release from internal
      stores: thapsigargin and 2,5-di(tert-butyl)-1, 4-benzohydroquinone deplete InsP3
      sensitive Ca2+ stores in glioma and in neuroblastoma-glioma hybrid cells.
AB  - Continuous superfusion of rat glioma cells with medium containing bradykinin
      (from 0.2 nM) induced a transient hyperpolarization followed by regular
      hyperpolarizing oscillations of the membrane potential. Similar repetitive
      hyperpolarizing oscillations were caused by extracellularly applied bradykinin or
      muscarine or by intracellularly injected GTP-gamma-S. The frequency of the
      oscillations was 1 per minute at bradykinin concentrations ranging from 0.2 nM to
      2 microM, but the amplitude and duration increased with rising peptide
      concentration. The muscarine-induced oscillations were blocked by atropine. In
      the presence of extracellular Ca2+, the substances thapsigargin, 2,5-di(tert
      butyl)-1,4-benzohydroquinone (tBuBHQ), and ionomycin reversibly suppressed the
      bradykinin-induced oscillations. Thapsigargin and tBuBHA, which are known to
      block the Ca2+ ATPase of endoplasmic reticulum, caused a transient rise in
      cytosolic Ca2+ activity, monitored with Fura-2, in suspensions of rat glioma
      cells or of mouse neuroblastoma-rat glioma hybrid cells. After a transient Ca2+
      rise caused by thapsigargin, tBuBHQ, or ionomycin, the Ca2+ response to
      bradykinin which is known to be due to release of Ca2+ from internal stores was
      suppressed. This indicates that thapsigargin and tBuBHQ deplete internal Ca2+
      stores as already seen previously for ionomycin. Thus, the inhibition of the
      membrane potential oscillations by thapsigargin, tBuBHQ, and ionomycin indicates
      that the oscillations are associated with activation of InsP3-sensitive Ca2+
      stores. In some cells composite oscillation patterns which consisted of two
      independent oscillations with different amplitudes that overlapped additively
      were seen. We discuss that this pattern and the concentration dependency of the
      oscillations could be due to "quantal" Ca2+ release from stores with different
      inositol 1,4,5-triphosphate sensitivities. Subsidence of the oscillations after
      omission of extracellular Ca2+ seems to be due to a lack of replenishment of the
      intracellular stores with Ca2+, which comes from the extracellular compartment.

PMID- 1397097
TI  - Mitotic apparatus formation and cleavage induction by micromanipulation of the
      nucleus and centrosome: the centrosome forms a spindle together with only the
      chromosomes at a short distance.
AB  - We micromanipulated the nucleus and centrosomes in the zygote of the starfish,
      Asterina pectinifera, in order to investigate their roles in mitotic apparatus
      formation and cleavage induction. The zygote cleaved without spindle formation
      when its nucleus was removed. When one or two centrosomes were transplanted, they
      formed asters in the recipient cell, which cleaved into three or four blastomeres
      so that each blastomere might contain one centrosome or aster. When one
      centrosome was removed, a half-spindle formed in the manipulated cell, which did
      not cleave until the other centrosome was duplicated. When both centrosomes were
      removed, no microtubular structures such as the spindle and the aster appeared in
      the manipulated cell, which failed to cleave. These results indicate that two
      centrosomes or more in the cell induce cleavage with or without the nucleus and
      that one centrosome or less does not induce cleavage. It is also concluded that
      the centrosome(s) together with the nucleus forms a half-spindle or bipolar
      spindle. However, from the experiments of nucleus transplantation and
      displacement, spindle formation is found to depend on the distance between
      chromosomes and centrosomes. The half-spindle formed when the distance from the
      centrosome to the chromosomes was shorter than 22 microns; on the other hand,
      when the distance was longer than 22 microns, the nucleus remained apart from the
      aster, which means that the functional range of the astral microtubule's ability
      to engage chromosomes was 22 microns from the centrosome.

PMID- 1397098
TI  - Enolase is present at the centrosome of HeLa cells.
AB  - Antibodies raised against the C-terminus and N-terminus region of gamma gamma
      enolase, as well as a polyclonal antibody raised against bovine brain gamma gamma
      enolase, were used to study the distribution of this glycolytic enzyme during the
      cell cycle in HeLa cells. Enolase was found to be present throughout the
      cytoplasm of both interphase and dividing cells. In addition, a portion of
      cellular enolase was detected at the centrosome throughout the cell cycle. The
      capacity of glycolytic enzymes to play a structural as well as a glycolytic role
      suggests that the presence of enolase at the centrosome may be correlated with
      the organization of both the interphase cytoskeleton and the mitotic spindle.

PMID- 1397100
TI  - Mitosis-arresting effect of the calcium channel inhibitor SK&F 96365 on human
      leukemia cells.
AB  - The effect of SK&F 96365 (1-(beta-[3-(4-methoxyphenyl)propoxyl]-4-
      methoxyphenethyl)-1H-imidazole hydrochloride), a recently synthesized inhibitor
      of receptor-mediated calcium entry, was investigated on human hematopoietic cell
      lines. We found that treatment of the T-cell leukemia line Jurkat with SK&F 96365
      inhibited the Ca2+ influx triggered by antibodies against the CD3/TCR complex,
      while the inositol trisphosphate-dependent Ca2+ release from intracellular stores
      remained intact. A 50% inhibition of the Ca2+ influx was obtained with 5 microM
      SK&F 96365, while higher concentrations of the drug blocked the CD3-dependent
      Ca2+ influx completely. In addition to its blocking of the Ca2+ influx, treatment
      with SK&F 96365 was found to accumulate mitotic cells. The drug (5 microM)
      imposed a total cell cycle arrest in G2/M. The mitosis block could be reversed by
      removal of the inhibitor from the cultures, while elevation of intracellular or
      extracellular Ca2+ did not restore cell cycle progression. This suggests that the
      cell cycle block induced by SK&F 96365 is not directly related to its action as
      an inhibitor of receptor-mediated calcium entry. Our findings indicate that SK&F
      96365, in addition to its ability to inhibit receptor-triggered Ca2+ influx,
      offers a new method for imposing a reversible mitosis arrest in hematopoietic
      cell lines.

PMID- 1397099
TI  - Proteolytic processing of the 72,000-Da type IV collagenase by urokinase
      plasminogen activator.
AB  - Regulation of the activity of proteolytic enzymes is of major importance in the
      turnover of connective tissues. The search for physiologically relevant
      activation mechanisms of principal tissue-degrading enzymes, e.g.,
      metalloproteinases, has therefore been of wide interest. We have now studied
      whether the initiating factor of the fibrinolytic system, urokinase plasminogen
      activator (u-PA), may also function in the early steps of activation of one of
      the metalloproteinases, the M(r) 72,000 gelatinase/type IV collagenase produced
      by cultured fibroblasts. Treatment of the secreted M(r) 72,000 proteinase by u-PA
      yielded a cleavage product of M(r) 62,000 as revealed by fluorography of
      radioactively labeled proteins as well as by gelatin zymography SDS-PAGE gels.
      The u-PA-catalyzed cleavage of the M(r) 72,000 proteinase was blocked by anti-u
      PA antibodies, but was unaffected by the plasmin inhibitor aprotinin, thus
      indicating a specific action for the activator. On the contrary, the tissue
      activator of plasminogen, t-PA, did not cleave the type IV collagenase in similar
      assays. u-PA-catalyzed cleavage of recombinant type IV collagenase, produced in a
      baculovirus expression system, yielded a similar M(r) 62,000 activity in
      gelatinolysis assay. Zymograms of the isolated pericellular matrices of cultured
      fibroblasts also revealed M(r) 72,000 gelatinolytic polypeptide that was
      converted to an M(r) 62,000 form by u-PA. Both polypeptides were recognized in
      immunoblotting by antibodies against the gelatinase/type IV collagenase,
      suggesting immunological identity with the secreted enzyme. Thus the M(r) 72,000
      gelatinase/type IV collagenase is not only secreted, but also deposited into the
      pericellular fibroblast matrix, and both forms are substrates for u-PA. The
      results suggest a new potential role for u-PA as a direct regulator of
      metalloproteinase-mediated extracellular proteolysis via the cleavage of the M(r)
      72,000 gelatinase/type IV collagenase to an M(r) 62,000 form.

PMID- 1397101
TI  - Differential proliferative response of cultured fetal and regenerating
      hepatocytes to growth factors and hormones.
AB  - Upon epidermal growth factor (EGF) stimulation, fetal (20 days of gestation) and
      regenerating (44-48 h after partial hepatectomy) rat hepatocytes, isolated and
      cultured under identical conditions, increased DNA synthesis and entered into S
      phase and mitosis, measured as [3H]thymidine incorporation and DNA content per
      nucleus in a flow cytometer, respectively. Fetal hepatocytes consisted of a
      homogeneous population of diploid (2C) cells. Two different populations of cells
      were present in regenerating liver, diploid (2C) and tetraploid (4C) cells, that
      responded to EGF. Glucagon or norepinephrine did not affect EGF stimulation of
      DNA synthesis in fetal liver cells, but they potentiated EGF response in
      regenerating hepatocyte cultures. Glucocorticoid hormones (dexamethasone)
      inhibited DNA synthesis in fetal hepatocyte cultures, an effect potentiated by
      the presence of glucagon or norepinephrine. In contrast, in regenerating
      hepatocytes, dexamethasone increased EGF-induced proliferation. EGF-dependent DNA
      synthesis was inhibited by TGF-beta in both fetal and regenerating cultured
      hepatocytes. TGF-beta action was partially suppressed by norepinephrine in
      regenerating hepatocytes, but was without effect in fetal hepatocyte cultures,
      whereas a synergistic action between TGF-beta and dexamethasone inhibiting growth
      in fetal but not in regenerating hepatocytes was found. Taken together, these
      results may suggest that there are significant differences between fetal and
      regenerating hepatocyte growth in their response to various hormones.

PMID- 1397102
TI  - Spermidine nuclear acetylation in rat hepatocytes and in logarithmically growing
      rat hepatoma cells: comparison with histone acetylation.
AB  - Spermidine acetylation has been studied in nuclear homogenates and in entire
      nuclei from rat hepatocytes and rat hepatoma tissue culture (HTC) cells, isolated
      at different stages of logarithmic growth, and compared to histone acetylation.
      Under all experimental conditions, N8-acetylspermidine was the predominant
      product of the reaction (90%). Unlike histone, spermidine acetylation in HTC cell
      and hepatocyte entire nuclei was almost absent or strikingly reduced relative to
      acetylation using nuclear homogenates as the enzyme sources. This was due to the
      lack of a free minor pool of spermidine, most likely lost during the purification
      of entire nuclei. Thus, preincubation of intact nuclei in the presence of
      spermidine restored activities to values observed using nuclear sonicates.
      Spermidine acetylation in HTC cell nuclei fluctuated moderately during cell
      growth, being stimulated immediately after initiation of proliferation and
      decreasing progressively as cultures reached high cell density. This pattern
      corroborated that of N8-acetylspermidine intracellular accumulation induced by
      culturing cells in the presence of 1 mM 7-amino-2-heptanone, a competitive
      inhibitor of N8-acetylspermidine deacetylase. Histone acetylation during HTC cell
      growth was not markedly different qualitatively from that of spermidine.
      Moreover, spermidine and histone acetylations in hepatocyte nuclei were of the
      same order of magnitude as those seen in rat hepatoma cell nuclei. Finally,
      inhibition of deacetylation of N8-acetylspermidine had no apparent deleterious
      effects on cell and growth. It remains to be determined whether the acetylation
      step is of higher physiological importance, in particular, and as discussed in
      nuclear spermidine turnover.

PMID- 1397103
TI  - The relationship between hsp 70 localization and heat resistance.
AB  - Using indirect immunofluorescence we have investigated the kinetics of nuclear
      accumulation and removal of hsp 70 in HA-1 Chinese hamster fibroblasts exposed to
      elevated temperatures. The kinetics of accumulation of hsp 70 in the nuclei were
      found to be time/temperature dependent at all temperatures tested (42-45 degrees
      C). At a given temperature, the fraction of cells manifesting nuclear
      localization of hsp 70 increased with exposure time. For a given duration of
      heating, the fraction of cells manifesting nuclear localization of hsp 70
      increased with the temperature. The kinetics of the nuclear accumulation of hsp
      70 were similar for normal HA-1 cells, their heat-resistant variants, and
      transiently thermotolerant cells (triggered by prior exposure to a brief heat
      shock or to sodium arsenite). Upon return to 37 degrees C after heat shock, the
      kinetics of removal of the hsp 70 associated with the nucleus was dependent on
      the severity of the initial heat challenge. However, for a given heat dose, the
      decay of nuclear localization of hsp 70 was more rapid in thermotolerant and heat
      resistant cells than in their normal counterparts. These results suggest that the
      increased levels of hsp 70 associated with the transient or permanently heat
      resistant state may play a direct role in restoring and/or repairing heat-induced
      nuclear and nucleolar alterations associated with heat-induced cell killing.
      Furthermore, they also suggest that the heat-resistant state may involve
      ameliorated repair of heat-induced cellular alterations.

PMID- 1397105
TI  - Induction of peroxisomal enzymes and a 64-kDa peptide in cultured mouse
      macrophages treated with clofibrate.
AB  - The presence of catalase-containing particles was demonstrated in mouse
      macrophages of the cell line J774.3. These cells were incubated with clofibrate,
      a hypolipidemic drug known to cause peroxisome proliferation in rodent
      hepatocytes. The specific activities of catalase and fatty acid oxidase were
      significantly increased after 48 h incubation with 2 mM clofibrate. This response
      proved to be time and dose dependent. Other organelle marker enzymes showed
      little change in activity. Unexpectedly, clofibrate treatment also produced an
      increase in a 64-kDa peptide in these cells.

PMID- 1397104
TI  - Basal levels of max are sufficient for the cotransformation of C3H10T1/2 cells by
      ras and myc.
AB  - The ras and myc oncoproteins cooperate to transform the established murine
      fibroblast cell line C3H10T1/2. To determine the impact of overexpression of the
      myc oncoprotein on the phenotype of C3H10T1/2 cells, two C3H10T1/2-myc clonal
      cell lines, SVc-myc 11A and myc neo 13A, were isolated and characterized.
      Although both C3H10T1/2-myc cell lines are morphologically indistinguishable from
      wild-type C3H10T1/2 cells and possess growth properties similar to those of
      C3H10T1/2 cells, each displays a predisposition to transformation following
      transfection with the activated form of the human H-ras gene. In C3H10T1/2 cells
      overexpressing the v-myc or H-ras oncogenes, the levels of mRNA encoding max, the
      recently identified oligomerization partner of myc, remain unchanged, suggesting
      that the endogenous level of max in C3H10T1/2 cells is sufficient for a high
      frequency of transformation by ras and myc. Based on these studies, the C3H10T1/2
      myc clonal cell lines we describe are suitable model systems for examining the
      molecular role of the myc protein in transformation and for characterizing
      additional factors that synergize with myc in multistep transformation.

PMID- 1397107
TI  - The phase of sperm flagellar beating is not conserved over a brief imposed
      interruption.
AB  - We have studied the phase component of flagellar beating by holding the head of a
      sea urchin sperm in the tip of a sinusoidally vibrating micropipet and then
      abruptly displacing the pipet laterally at a speed of 2.5 microns/ms for various
      durations. This rapid displacement of the pipet delayed the initiation of the
      next bend for as long as the displacement continued, up to a duration of 1 beat
      cycle, corresponding to a delay of 0.5 beat cycle. At the end of this
      displacement, the movement of the pipet was stopped completely without resumption
      of the initial vibration. Analysis of the flagellar waveform showed that
      immediately when the pipet was stopped, the flagellum started to beat by
      spontaneously initiating the bend that had been delayed. The flagellum then
      continued steady-state beating, with normal waveform and a new phase that was
      independent of the original phase of beating. These data suggest that the
      information on the phase of beating is located only at the basal end of the
      flagellum, and not in oscillators distributed along the axoneme. After this
      information has been lost, the flagellum can resume beating at any arbitrary
      phase relative to its original phase.

PMID- 1397106
TI  - Phosphorylation of Xenopus elongation factor-1 gamma by cdc2 protein kinase:
      identification of the phosphorylation site.
AB  - The cdc2 protein kinase phosphorylates elongation factor-1 gamma (EF-1 gamma)
      during meiotic maturation of Xenopus oocytes. A synthetic peptide P2:
      PKKETPKKEKPA matching the cDNA-deduced sequence of EF-1 gamma was an in vitro
      substrate for cdc2 protein kinase and inhibited phosphorylation of EF-1 gamma.
      Tryptic hydrolysis of EF-1 gamma and the P2 peptide, both phosphorylated by cdc2
      protein kinase, resulted in multiple partial digestion products generated by the
      presence of barely hydrolysable bonds. The two peptides obtained from the
      hydrolysis of EF-1 gamma comigrated exactly in two-dimensional separation with
      two of the P2 peptide hydrolysates. EF-1 gamma therefore contains one unique
      phosphoacceptor for cdc2 protein kinase, identified as threonine-230.

PMID- 1397108
TI  - Streptococcal infection in general practice.

PMID- 1397109
TI  - Streptococcal pharyngitis in general practice. 1. Some unusual features of the
      epidemiology.
AB  - This report is based on a study of acute infections of the upper respiratory
      tract in 1965 and detailed records of such infections in 1963 and 1964. A change
      from illnesses mainly yielding viruses to illnesses mainly yielding group A
      streptococci was noted around the age of 5 years. A positive culture for group A
      streptococci in patients over 4 years of age was highly correlated with a
      complaint of sore throat and with serological evidence of streptococcal
      infection. A bimodal age distribution curve for pharyngitis associated with a
      positive culture for group A streptococci was consistently noted. The incidence
      was highest in children aged 5-9 but a second smaller peak occurred among adults
      in the 30-39 age group. The evidence suggests that being female increases the
      risk of acquiring group A streptococci and of experiencing sore throat.

PMID- 1397110
TI  - Streptococcal pharyngitis in general practice. 2. A note on dual infection and
      transient urinary abnormalities.
AB  - In an incomplete study in 1965 microscopic haematuria in the second or third week
      after acute pharyngitis was found four times more often in patients with either
      microbiological or clinical evidence of dual infection with both group A
      streptococci and a virus than in patients with evidence only of infection with
      group A streptococci. Prospective studies of the role of viruses in the aetiology
      of transient haematuria and of acute post streptococcal glomerulonephritis are
      feasible in general practice and would be most productive if concentrated in
      children 5-9 years of age.

PMID- 1397111
TI  - Splenomegaly in acute infections due to group A streptococci and viruses.
AB  - Over a period of 9 years in general practice temporary enlargement of the spleen
      was found in 29 episodes of pharyngitis or tonsillitis, in 2 episodes of acute
      upper respiratory tract infection other than pharyngitis and in 6 episodes of
      acute cervical lymphadenitis. In five patients more than one episode of illness
      associated with splenomegaly was recorded. In 26 of the 37 episodes a possible
      aetiology was identified. Evidence only of infection with group A streptococci
      was found in 14 episodes, adenoviruses or coxsackie B viruses were isolated alone
      in 4 episodes and in 4 episodes the only finding was the presence in the blood of
      more than occasional atypical mononuclear cells; in 4 episodes there was evidence
      of both streptococcal and viral infection. Episodes with evidence of
      streptococcal infection only tended to be of shorter duration and to be more
      evenly distributed over the year than were episodes without such evidence.
      Temporary splenomegaly was noted also in two children with varicella (one of whom
      also had streptococcal infection) and in an adult with probable rubella.

PMID- 1397113
TI  - Transmission of Neisseria meningitidis among asymptomatic military recruits and
      antibody analysis.
AB  - Following the occurrence of a case of systemic meningococcal disease in a
      military camp in Norway, throat cultures and blood samples were collected from 33
      healthy individuals belonging to the same troop as the patient (troop A) and from
      29 individuals from a different troop (troop B) in the same camp. Serological
      studies showed that 91% of the recruits had bactericidal antibodies against the
      disease-causing strain. The isolates of Neisseria meningitidis recovered from the
      throat cultures were serogrouped, serotyped, and assigned to a clone on the basis
      of an analysis of the electrophoretic mobilities of 14 metabolic enzymes. None of
      the 23 carriers in troop A harboured the clone responsible for the case of
      disease, but 6 carried isolates of the same electrophoretic type, ET-7, which was
      not identified in any of the 19 carriers of troop B. Individuals in troop A were
      resampled 2 and 17 weeks after the meningococcal disease episode. Five of the
      carriers had acquired different clones and one of them changed clone twice in
      that period. Four of the six newly acquired clones had previously been identified
      in other carriers of troop A, demonstrating transmission of clones among
      individuals living and working in close proximity.

PMID- 1397112
TI  - A one-year study of streptococcal infections and their complications among
      Ethiopian children.
AB  - Post-streptococcal complications are known to be common among Ethiopian children.
      Little is known, however, about the epidemiology of beta-haemolytic streptococci
      in Ethiopia. A total of 816 children were studied during a one-year period: 24
      cases of acute rheumatic fever (ARF), 44 chronic rheumatic heart disease (CRHD),
      44 acute post streptococcal glomerulonephritis (APSGN), 143 tonsillitis, 55
      impetigo, and 506 were apparently healthy children. Both ARF and APSGN occurred
      throughout the year with two peaks during the rainy and cold seasons. The
      female:male ratio among ARF patients was 1.4:1 and 1:1.9 among APSGN. The monthly
      carrier rate of beta-haemolytic streptococci group A varied from 7.5-39%, average
      being 17%. T type 2 was the most frequent serotype. Marked seasonal fluctuations
      were noted in the distribution of serogroups among apparently healthy children.
      Beta-haemolytic streptococci group A dominated during the hot and humid months of
      February-May. Strains were susceptible to commonly used antibiotics, except for
      tetracycline.

PMID- 1397114
TI  - The serological grouping system for Serpulina (Treponema) hyodysenteriae.
AB  - Lipopolysaccharide from serostrains of Serpulina (Treponema) hyodysenteriae for
      serogroups A to I was characterized using sodium dodecylsulphate polyacrylamide
      gel electrophoresis and silver staining. All strains had lipopolysaccharide
      components ranging from 10 to 16 kDa that represented lipid A-core polysaccharide
      regions, and short O-antigen side chain were also recognized in certain
      immunoblots. Serological reactions between lipopolysaccharide and antisera
      against each of these serostrains were examined by Western immunoblotting. There
      was relatively little antigenic cross-reactivity between LPS from the nine
      strains, thus confirming their suitability as serostrains. Using cross-absorbed
      sera, isolates within serogroups A and E were shown to possess unique epitopes on
      the core lipopolysaccharide, distinct from serogroup reactivities. These isolates
      were therefore identified as serovars within the serogroups. This study confirmed
      the usefulness of the serotyping scheme for S. hyodysenteriae, in which the
      bacteria can be placed into serogroups using unabsorbed sera, and into serovars
      within these using cross-absorbed sera.

PMID- 1397115
TI  - Concordance of auxotype/serovar classes of Neisseria gonorrhoeae between sexual
      contacts.
AB  - One hundred and three known sexual-contact pairs of patients with culture-proven
      gonorrhoea who attended St Mary's Hospital, London between May 1989 and February
      1991 were identified. All isolates from these patients were serotyped and
      auxotyped and compared for type concordance within sexual-contact pairs. Serotype
      was concordant in 80 (78%) of 103 sexual-contact pairs, auxotype in 88 (85%) and
      auxotype/serovar (A/S) class in 66 (64%) on the first screening. All pairs of
      isolates showed concordance in both serotype and auxotype when typing was
      repeated using a single set of serotyping reagents and of auxotyping media.
      Seventeen serovars, 9 auxotypes and 36 A/S classes were found in this population.
      Our results suggest that both serotyping and auxotyping may be used as markers to
      allow tracing of sexual-contact pairs, but that a single set of reagents should
      be used to ensure maximum reliability.

PMID- 1397117
TI  - Serological cross-reaction between Legionella pneumophila and campylobacter in
      the indirect fluorescent antibody test.
AB  - Sera from 50 patients with culture-proven campylobacter gastroenteritis were
      examined for the presence of antibodies to Legionella pneumophila. Ten patients
      (20%) had a positive titre (> or = 16) as measured by indirect
      immunofluorescence. Antibodies were detected in only 1 of 36 acute sera but in 10
      of 14 (71%) sera obtained more than 10 days after the onset of symptoms. All
      positive sera contained specific IgM antibodies but specific IgG or IgA could not
      be detected in any sample. No legionella antibodies could be detected in sera
      from 42 similar patients with salmonella gastroenteritis. These results were
      shown to be due to serological cross-reaction between L. pneumophila and
      campylobacter.

PMID- 1397116
TI  - Virulence factors of enteric Escherichia coli in young Aboriginal children in
      north-west Australia.
AB  - Enterotoxigenic Escherichia coli (ETEC) were the most frequently identified
      enteric pathogens associated with diarrhoea in 0-5 year old Aboriginal children
      in tropical north-west Australia with an incidence similar to those from other
      tropical regions. Heat-stable toxin-producing (ST+) strains were associated with
      diarrhoea throughout the year but heat-labile toxin-producing (LT+) strains were
      more important in the monsoonal summer season. ST+ strains were commonest in
      children with diarrhoea between 6 and 18 months of age while LT+ strains were
      associated with diarrhoea in children aged 18-24 months. Vero-toxigenic E. coli
      (VTEC) which produced VT1, but not VT2, and enteroadherent (EAF+) E. coli were
      significant causes of diarrhoea, mainly in children below 18 months but without a
      seasonal pattern.

PMID- 1397118
TI  - Serological responses of chickens experimentally infected with Salmonella
      enteritidis PT4 by different routes.
AB  - Commercially reared chickens were challenged with Salmonella enteritidis phage
      type (PT) 4 by aerosol, or via the conjunctiva. Inhalation of 2.9 x 10(2) or 4.2
      x 10(3) S. enteritidis resulted in the production of IgG antibodies to the
      lipopolysaccharide (LPS) of S. enteritidis PT4. When the aerosol inoculum was
      increased to 2.4 x 10(5) bacteria per bird the antibody produced were
      predominantly of the IgM-class. Chickens challenged with 10(3) S. enteritidis PT4
      via the conjunctiva mounted only a poor immune response. Increasing the challenge
      dose to 10(8) S. enteritidis resulted in the production of high-titre serum
      antibodies of both the IgG and IgM classes. Results from this study suggest that
      aerosols containing small numbers of S. enteritidis PT4 might be responsible for
      intraflock infection of poultry.

PMID- 1397119
TI  - Accumulation of crystallin in developing chicken lens.
AB  - Separation and quantitation of crystallin subunits in embryonic and post-hatched
      chicken lens were carried out by two-dimensional gel electrophoresis and an image
      analysing system in order to elucidate detail in the accumulation process of each
      crystallin subunit in lens differentiation. Complete separation of the subunits
      was possible when 7 M urea was included in the second dimension gel of the
      electrophoresis. In particular, beta-crystallin could be separated into more than
      24 spots on the gel. These experiments showed that delta-crystallin accumulated
      rapidly during early development up to more than 80% of total crystallins, while
      beta-crystallin accumulated quickly only after hatching. In contrast with the
      contents of beta- and delta-crystallins, alpha-crystallin content in total
      crystallins was kept at approximately 18% throughout lens development. Therefore,
      it was concluded that crystallins accumulated in several different ways. This
      suggests that different regulation mechanisms work on the accumulation of each
      crystallin subunit and that the subunit composition of lens proteins is specific
      to each state of lens development.

PMID- 1397120
TI  - Oxygen kinetics in preretinal perfluorotributylamine.
AB  - Previous studies have relied on various electrodes or probes to monitor
      preretinal oxygen tension in an effort to gain insight into retinal oxygenation.
      In order to corroborate and extend the results of such studies, we developed a
      relatively non-invasive method of determining preretinal oxygen tension using 19F
      nuclear magnetic resonance (NMR) spectroscopy. Small liquid perfluorocarbon
      (LPFC) droplets were injected into the preretinal vitreous space of the rabbit
      eye. The T1 value obtained from the fluorine nuclide could then be used to
      determine preretinal oxygen tension (PO2) with a high degree of sensitivity,
      since the fluorine spin-lattice relaxation rate (T1)-1 in LPFCs is directly
      proportional to PO2 under conditions of no flow and known temperature. In the
      present study, we investigated the oxygen uptake and clearance rates from small
      preretinal droplets of the LPFC perfluorotributylamine (FTBA) in response to step
      changes in arterial PO2. At all FTBA volumes examined (2, 10 and 100
      microliters), the oxygen uptake and clearance curves were well approximated by a
      simple exponential equation with mean time constants 9.8/15.3, 21.4/19.4 and
      77.7/45.3 min (uptake/clearance), respectively. Following return to normoxemic
      (baseline) conditions, FTBA droplets provided a preretinal PO2 of 39.4 +/- 9.2
      mmHg (mean +/- S.D., n = 12). The 19F NMR method provides a measure of steady
      state preretinal PO2 that independently verifies and complements information
      obtained using oxygen-sensitive microelectrodes or probes. However, the long time
      constants for oxygen uptake and clearance, particularly in FTBA volumes on the
      order of 10 microliters and greater, may represent a practical limitation of this
      method for determining rapid oxygen flux in the preretinal vitreous
      space.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397121
TI  - Structural studies on beta H-crystallin from bovine eye lens.
AB  - Bovine lens beta H-crystallin, isolated at pH 6.7, undergoes reversible
      dissociation into dimers and an intermediate size of oligomer (peak A) at pH 5.4.
      Peak A is enriched in the beta B1 subunit but lacks beta B2, whereas beta B2 is a
      major component of the dimers. A method for isolation of beta B1 from peak A is
      described. The pH dependence of the dissociation-reassociation suggests that
      histidines on the surface of the dimers become buried in the assembly of beta H
      crystallin. The positions of the four histidines on the surface of the compact
      domains of each subunit of the beta B2 homodimer are shown. The beta B1-enriched
      oligomer has a much lower solubility compared with the beta B2 containing beta H
      crystallin. It is possible that beta B2 plays a role in solubilizing beta
      crystallin aggregates.

PMID- 1397122
TI  - Concerning the symmetry of the 'hexagonal' cells of the corneal endothelium.
AB  - Modeling studies are presented to show how the figure coefficient and hexagon
      deviation index values decrease as a six-sided endothelial cell is systematically
      distorted from a completely symmetrical geometric shape (a regular hexagon). By
      use of scanning electron micrographs of rabbit corneal endothelium and an
      analysis of published specular micrographs of rabbit corneal endothelium, it is
      shown that the six-sided cells are not necessarily very symmetrical. Such cells
      should thus be reported as six-sided cells rather than as 'hexagons' which
      carries the inherent risk of implying regularity (and thus supposed stability in
      a tesselated mosaic) of such cells.

PMID- 1397123
TI  - Changes in Muller cell plasma membrane specializations during subretinal scar
      formation in the rabbit.
AB  - The aim of this study was to identify changes in Muller cell plasma membrane
      specializations during experimentally induced subretinal gliosis in rabbits. When
      rabbits are dosed with sodium iodate, large expanses of retinal pigment
      epithelium and photoreceptors are destroyed. They are replaced by a subretinal
      scar consisting mainly of the ascending processes of Muller cells. These
      processes transform from the slender, highly polarized structures seen in normal
      animals into irregular processes that form a glia limitans along the basement
      membrane of the pigment epithelium, left bare following its degeneration. As the
      scar processes extend through the subretinal space and contract this basement
      membrane, they undergo dramatic changes in shape that are especially apparent in
      three-dimensional computer reconstructions of serial thick sections examined by
      high-voltage electron microscopy. Other changes involve the intercellular
      junctions and apical microvilli normally associated with the external limiting
      membrane. These structures become scattered over the surfaces of the ascending
      processes and are eventually lost. Loss of microvilli is associated with
      disappearance of immunostaining for a specific glycoconjugate normally associated
      with the microvillar plasma membrane. The observations document profound changes
      in Muller cell structural and functional polarity during subretinal scar
      formation.

PMID- 1397124
TI  - Enhanced expression of the growth-regulated calcyclin gene during corneal wound
      healing.

PMID- 1397125
TI  - Histone deposition and metabolism in embryonic chick lenses during
      differentiation.

PMID- 1397127
TI  - Transplantation of embryonic retina to the subretinal space in rabbits.
AB  - Embryonic rabbit retina can be transplanted to the subretinal space of adult
      rabbit with a new method, which gives a high rate of successful short-term
      transplants. Embryonic (stage E 15) neural retina cells were injected through an
      incision just behind the sclerocorneal border with a thin (inner diameter 0.15
      0.4 mm, outer diameter 0.3-0.5 mm) plastic tube attached to a specially designed
      instrument, by which the length of the protruding plastic tip could be
      controlled. The retina was penetrated from the vitreous side and the donor tissue
      was injected into the subretinal space. The cells survived in the host for at
      least 5 months, although the long-term survival rate tended to decrease. The
      transplanted cells matured and differentiated, forming an approximation of the
      layered, retinal structure with some anomalies (e.g. rosettes). The subretinal
      location offers an interesting and convenient way of studying the development of
      retinal cell transplants in rabbits. Large transplants can be produced, and the
      risk for failures due to erroneous vitreous placement is small.

PMID- 1397126
TI  - CD68 antigen expression by human retinal pigment epithelial cells.
AB  - Although a primary role of the retinal pigment epithelium (RPE) is the
      phagocytosis of aged outer segment membranes, the RPE may also phagocytize
      particulates via several specific receptors that are characteristically present
      on mononuclear phagocytes of bone marrow origin. In recent immunophenotypic
      studies, CD68 monoclonal antibodies (mAb) have been shown to react selectively
      with a specific 110 kDa cytoplasmic glycoprotein present in mononuclear
      phagocytes from various sources. Designated as anti-macrophage antibodies that
      react with this macrophage-associated antigen, CD68 antibodies are now widely
      used for immunohistochemical identification of mononuclear phagocytes. Using a
      panel of CD68 mAb (KP1, EMB11, Ki-M6, Y1/82A, and Y2/131) we performed
      immunohistochemistry on three cytospin preparations of freshly isolated human RPE
      cells, three primary human RPE cultures, and 12 human RPE cell lines maintained
      in culture for up to 40 passages. Cytospin preparations of freshly isolated RPE
      cells demonstrated heavy reactivity in 5% of cells. Five- to 7-day-old primary
      RPE cultures exhibited uniform, heavy staining of all cells. Strong
      immunohistochemical reactivity persisted in all 12 cell lines at various passages
      up to and including passage 40. Stimulation of cultured RPE cells with interferon
      gamma (100 U ml-1) for 24 and 48 hr did not produce observable differences in
      CD68 staining. RPE cells failed to stain when control mAb or mouse serum were
      substituted for the primary antibody. The constitutive expression of CD68 by
      neuroectodermally-derived RPE cells extends their immunophenotypic similarities
      with mesenchymally-derived mononuclear phagocytes and provides an additional
      antigenic marker to identify RPE cells in vitro.

PMID- 1397129
TI  - Two cone types of rat retina detected by anti-visual pigment antibodies.
AB  - The presence of two distinct cone types was demonstrated in the retina of the rat
      using two cone-specific monoclonal anti-visual pigment antibodies. Cones labelled
      by antibody COS-1 constituted the large majority (about 93%) of cones, and are
      most probably responsible for the green photopic sensitivity of the rat. About 7%
      of the cones were recognized by antibody OS-2, and are thought to be blue
      sensitive elements. While OS-2 positive cones were evenly distributed throughout
      the retina, there were slight differences in the distribution of COS-1 positive
      cones. The cones made up about 0.85% of all photoreceptor cells. Although the OS
      2 positive cones occur in a very low number (0.05% of all photoreceptors) and
      probably do not appreciably contribute to the photopic system of the rat, their
      presence in the rat strengthens the presumption that most mammalian species
      exhibit a dual cone system with a shortwave and a middle-to-longwave sensitivity.

PMID- 1397128
TI  - Ischaemia- and reperfusion-induced Na+, K+, Ca2+ and Mg2+ shifts in rat retina:
      effects of two free radical scavengers, SOD and EGB 761.
AB  - Using Sprague-Dawley rats with transient (90-min) regional ischaemia induced by
      retinal artery occlusion in the eye, we have shown that superoxide dismutase
      (SOD) and EGB 761 (IPSEN, France), two free radical scavengers, can dramatically
      reduce the reperfusion-induced sodium and calcium gains, and potassium loss in
      retinal tissue. Investigating whether this was a 'direct' protective effect,
      operating during reperfusion, or an 'indirect' effect arising from the action of
      SOD or EBG 761 on the tissue during ischaemia. SOD (15,000 U kg-1) and EGB 761
      (100 mg kg-1) were added to the rats at the moment of reperfusion (after an
      ischaemic insult). Eyes were subjected to 90 min ischaemia followed by 4 and 24
      hr of reperfusion, respectively. In the drug-free control group, 90 min of
      ischaemia resulted in an accumulation of retinal sodium (2-fold) and calcium (3
      fold), and a loss of cell potassium (by 40%) and magnesium (by 40%). During the
      first 4 hr of reperfusion the ionic imbalance was unchanged, while after 24 hrs
      of reperfusion a normalization was observed and the ion content of the retina
      almost returned to their preischaemic values. SOD and EGB 761 treatment
      significantly reduced the reperfusion-induced ionic imbalance (magnesium was an
      exception) and improved the recovery of retinal ion contents. Our results
      indicate that the elimination of oxygen radicals by free radical scavengers may
      reduce the reperfusion-induced ionic imbalance and improve the ionic homeostasis
      in the injured retinal cells.

PMID- 1397130
TI  - Kynurenine identified as the short-wave absorbing lens pigment in the deep-sea
      fish Stylephorus chordatus.
AB  - A number of deep-sea fish have bright yellow lenses whose coloration is
      attributable to a variety of largely unidentified short-wave absorbing pigments.
      Here the pigment of the deep-sea fish Stylephorus chordatus has been isolated and
      identified by NMR and mass spectroscopy as kynurenine; a pigment also found in
      the human lens. The degree of this pigmentation is greater in older animals. The
      fact that the lenses of both a deep-sea fish and man contain the same pigment is
      of interest, given the vastly different light environments they inhabit.

PMID- 1397131
TI  - The effects of isovolumic hemodilution on ocular blood flow.
AB  - Techniques by which retinal blood flow may be increased safely are potentially
      important in the treatment of retinal vascular disease. It was hypothesized that
      hemodilution, which increases cerebral blood flow, would also increase retinal
      blood flow. To investigate the physiological effects of hemodilution in the eye,
      ocular blood flow was measured in 14 cats using the radioactively labeled
      microsphere method. After the animals were anesthetized with halothane and
      oxygen, intraocular and systemic arterial pressure were recorded; blood flows
      were measured before and after isovolumic hemodilution to a hematocrit of 20-22%
      using 6% hydroxyethyl starch (a synthetic plasma expander with a molecular weight
      of 450 in 0.9% saline). In hemodiluted cats, retinal blood flow increased 71%
      from its baseline value (36.7 +/- 6.4 ml 100 g-1 min-1 to 62.9 +/- 6.4 ml 100 g-1
      min-1, mean +/- S.E.M., P < 0.0001). Calculated retinal O2 delivery remained
      approximately constant, as the increased blood flow countered a significant
      decrease in arterial O2 content. Choroidal blood flow decreased (1297 +/- 140 ml
      100 g-1 min-1 to 1051 +/- 144 ml 100 g-1 min-1) but the change was not
      statistically significant. Blood flows in the iris and sclera were not
      significantly altered. Hemodilution increased retinal blood flow without causing
      a redistribution in ocular blood flow.

PMID- 1397132
TI  - Morphologic and molecular changes during the post-natal development of the rabbit
      vitreous.
AB  - Rabbits aged 1, 4, 10, 15, and 20 days, and 4 months were anesthetized and
      perfused with 4% formaldehyde. One eye of each rabbit was processed for paraffin
      embedding, while the other eye was embedded intact in methacrylate. Rabbits aged
      1 and 15 days and 4 months were perfused with 2.5% glutaraldehyde, and the eyes
      were processed for Epon embedding. The paraffin sections were immunostained to
      allow detection of a high molecular weight cartilage matrix glycoprotein (CMGP),
      which is synthesized by the ciliary body and found in the vitreous in adult
      animals, using a specific mouse monoclonal antibody. CMGP was identified in the
      vitreous and in the inner layer of the ciliary epithelium only after the
      fifteenth day of life in amounts comparable to those detected in adult rabbits.
      Before this time immunostaining with the monoclonal antibody was seen only in the
      apical region of the inner ciliary epithelial cells. However, electron
      microscopic observations revealed that the cytoplasmic organelles responsible for
      the secretion of glycoproteins, i.e. the rough endoplasmic reticulum, Golgi
      apparatus, and vesicles, were present in the inner layer of ciliary epithelial
      cells as early as the first day of life. Anteroposterior sections of whole eyes
      embedded in methacrylate revealed a relatively dense meshwork of vitreous fibrils
      on the first day of life. The blood vessels were concentrated at the posterior
      region of the lens, and isolated cells were visible. The blood vessels were not
      seen after the age of 15 days, and the fiber meshwork and cells were
      inconspicuous by then.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397133
TI  - Relations among IOP reduction, ocular disposition and pharmacology of the
      carbonic anhydrase inhibitor ethoxzolamide.
AB  - We have measured sequentially the concentrations of ethoxzolamide (6
      ethoxybenzothiazole-2-sulfonamide) in ocular tissues following its intravenous or
      topical administration to normal albino rabbits. This was done in parallel with
      determinations of intraocular pressure (IOP) measured by tonometer or direct
      manometry. Ethoxzolamide was used because of its very high activity against
      carbonic anhydrase and experience showing that there is little or no other
      receptor in tissues. During the course of these experiments it was discovered
      that the lipid-soluble ethoxzolamide is converted in vivo to a water-soluble
      metabolite, while retaining high activity against the enzyme. Presumably this is
      the 6-O-glucuronide adduct. At the minimal dose for maximal effect (4 mg kg-1
      i.v. at 45 min) the IOP lowering was 4.2 mmHg, the concentration in anterior uvea
      was 2.5 mumol kg-1, and the fractional inhibition of the enzyme (i) was 0.9995.
      The effect of free drug in the anterior uvea and other tissues. Following topical
      administration i was measured as a function of drug and enzyme in ciliary
      process. IOP lowering at 1 hr was -1.9 mmHg and i = 0.9993. By 4 hr i = 0.9980
      and the pharmacological effect disappeared. At 8 hr the concentration of
      ethoxzolamide in the ciliary process is 0.4 mumol kg-1, essentially that of
      enzyme, with no free drug present: drug is now a marker for enzyme. Ethoxzolamide
      also labels the red cell carbonic anhydrases in the rabbit as well as other
      species including man. There appears to be no ethoxzolamide receptor other than
      carbonic anhydrase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397134
TI  - Ocular pharmacokinetics of lens epithelial cell-specific immunotoxin 4197X-RA.
AB  - The ocular clearance, stability and systemic distribution of a lens epithelial
      cell-specific immunotoxin were evaluated in adult Dutch Belted rabbits.
      Immunotoxin 4197X-RA was prepared from a murine monoclonal antibody conjugated by
      a disulfide linkage to ricin A. After intracameral (i.c.) injection, clearance of
      the immunotoxin from the eye followed a first-order process. The half-life (t1/2)
      of immunotoxin in the aqueous humor was 51 min. Accumulation of the immunotoxin
      in ocular tissues appeared to be associated with aqueous outflow tracts, as it
      was primarily confined to the iris and the limbal regions of the cornea. No acute
      metabolism of immunotoxin was observed in the anterior chamber. The immunotoxin
      was detected in the blood 20 min post-injection and achieved a steady-state level
      after 40 to 180 min. A slow decline in labeled protein was then observed from 180
      min to 24 hr. Systemic clearance of the immunotoxin appeared to occur primarily
      by way of the kidneys. The present data indicate that immunotoxin 4197X-RA, like
      other large proteins, is passively cleared from the anterior chamber by aqueous
      flow, and that little or no acute breakdown occurs in the anterior chamber. It is
      anticipated that these data, along with results from cytotoxicity studies, will
      result in the determination of optimal doses and frequency of administration for
      the use of immunotoxin in human clinical trials.

PMID- 1397135
TI  - Aqueous humor hydrogen peroxide analysis with dichlorophenol-indophenol.
AB  - Hydrogen peroxide is now reported to be a normal aqueous humor component present,
      in the low microM concentration range, in the animal species which have been
      studied. This finding was established with the exclusive use of the
      dichlorophenol-indophenol method of analysis. In this procedure, aqueous humor is
      added to a blue, oxidized dichlorophenol-indophenol solution. The 605 nm
      absorbance of this solution immediately decreases in response to the reducing
      action of ascorbate present in the sample. The extent of reoxidation of the
      solution upon the addition of peroxidase, as measured by the increase in its 605
      nm absorbance, can be quantitatively related to the concentration of H2O2 in the
      sample. A close examination of this method revealed that reduced dichlorophenol
      indophenol spontaneously reoxidizes at a rate of 0.03 nmol min-1 microM-1, with
      generation of H2O2. H2O2 generation was unequivocally established by analysis of
      the temporal dependency of the absorbance increase produced by peroxidase in the
      absence of added H2O2 and by the sensitivity of this phenomenon to catalase. This
      spontaneous production of H2O2, on the other hand, cannot be attributed to
      ascorbate auto-oxidation because added ascorbate quantitatively reacts with
      dichlorophenol-indophenol, provided that an excess of the latter is maintained.
      This method then has an enormous potential to overestimate H2O2 in any sample. On
      the other hand, the response of the assay system to a given level of H2O2 depends
      on the level of reduction previously produced by ascorbate. This results in an
      artifactual positive correlation between ascorbate and H2O2 levels in samples
      containing variable amounts of ascorbate. In spite of these serious limitations
      the method can still be useful to measure H2O2 if appropriate precautions are
      taken. When using it for the analysis of rabbit aqueous humor H2O2 without
      correcting for the H2O2 generated during the assay and ignoring differences in
      the level of ascorbate in the samples, we obtained an average value of 25.3
      microM H2O2, which coincides with that reported in the literature for the rabbit,
      but is obviously incorrect. When analysing aqueous humor there was the additional
      variable of the aqueous humor itself inhibiting the rate of dichlorophenol
      indophenol auto-oxidation and so the final, corrected figure for H2O2
      concentration in the aqueous humor became uncertain, since the auto-oxidation of
      the substrate could not be properly subtracted.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1397136
TI  - Docosahexaenoic acid increases in frog retinal pigment epithelium following rod
      photoreceptor shedding.
AB  - The vertebrate retina conserves docosahexaenoic acid (22:6n-3) during n-3 fatty
      acid deficiency. The mechanism of conservation is not known, although recycling
      of this fatty acid between the retinal pigment epithelium (RPE) and retina is one
      possibility. We examined the role of the RPE in conservation of 22:6n-3 by
      quantitating the fatty acids and phospholipid molecular species (PLMS) in frog
      RPE before and after light-stimulated shedding of rod outer segments (ROS). RPE
      cells were dissociated with brush agitation and purified by a discontinuous
      ficoll density gradient. One hour after the light-induced shedding of ROS, the
      phagocytosed ROS tip and opsin content of RPE had increased. Simultaneously, the
      levels of 22:6n-3 and 22:6(n-3)-containing PLMS were increased in the RPE. Within
      8 hr following the shedding event, 22:6n-3 in the RPE had returned to the dark
      level. These findings indicate that the phagocytosed ROS tips contain 22:6n-3 and
      that the RPE metabolizes these ROS tips and eliminates 22: 6n-3 from the cell.
      Thus, the RPE is intimately involved in the metabolism of 22: 6n-3 in the retina.
      The recycling of 22: 6n-3 from the RPE to the retina is a possible means of
      conserving this important fatty acid in the retina.

PMID- 1397137
TI  - Synaptic potentials produced in jaw-closer and jaw-opener motoneurons by palatal
      stimulation.
AB  - Excitation and inhibition of temporal and digastric motoneurons (Temp. and Dig.
      Mns) during transient jaw closing, the so-called jaw-closing reflex, were studied
      in cats. Application of diffuse pressure stimulation to the posterior palatal
      surface produced the jaw-closing reflex and it was found that mechanosensory
      inputs from the posterior palatal mucosa produce depolarizing potentials on the
      Temp. Mns responsible for jaw closure during the jaw-closing reflex. We have
      demonstrated that in one-third of 27 explored Temp. Mns the initial bursts of
      spikes were elicited before the onset of jaw closure, suggesting that these cells
      contribute to initiate jaw closure during the jaw-closing reflex. The remaining
      cells probably contributed to maintain the occlusal phase. Furthermore, it was
      found that mechanosensory inputs from the posterior palatal mucosa produce a
      hyperpolarization-depolarization sequence in the Dig. Mns responsible for the jaw
      closing reflex. In addition, when pressure stimulation was applied to the
      anterior palatal mucosa, sustained jaw opening was elicited and an increase of
      firing frequency of Dig. Mns occurred 40 ms before the onset of jaw opening and
      continued for 80 ms.

PMID- 1397139
TI  - Induction of high frequency activity in the somatosensory thalamus of rats in
      vivo results in long-term potentiation of responses in SI cortex.
AB  - Extracellular single-unit techniques were employed to record unitary activity
      simultaneously from the thalamic ventral posterior medial (VPM) nucleus and the
      ipsilateral primary somatosensory cortex of adult rats. Cross-correlation
      analysis triggered by the spontaneous firing of thalamocortical relay neurons in
      VPM and the discharge of layer IV neurons in the corresponding ipsilateral
      cortical barrel indicated that the paired-units included in this study were
      strongly correlated in their activity. The baseline responses of highly
      correlated cortical/thalamic pairs to a 10 ms deflection of a vibrissa on the
      contralateral side were measured using poststimulus time histograms. After
      establishing the baseline response, high frequency activity in VPM was induced in
      one of two ways: i) direct electrical stimulation of thalamic neurons or ii)
      whisker stimulation in the presence of bicuculline methiodide (BIC) released near
      the thalamic neurons. Both methods resulted in a conditioning stimulus (CS)
      paradigm consisting of "burst" of high-frequency activity (50-100 Hz) with an
      inter-burst interval of 150 ms (approximately 7 Hz). Almost immediately following
      the presentation of the CS, the response of layer IV cortical neurons to vibrissa
      stimulation increased by 37-62% over baseline values, which was maintained after
      the effects of BIC had worn off in VPM. This enhancement in the response of the
      cortical neurons was not accompanied by a concomitant increase in the thalamic
      responses. Thus, these results strongly suggest that the potentiation first
      occurred at the thalamocortical synapse.

PMID- 1397138
TI  - Two modes of cerebellar input to the parietal cortex in the cat.
AB  - The characteristics of cerebellar input to the parietal cortex through the
      ventroanterior-ventrolateral (VA-VL) complex of the thalamus were investigated in
      the adult cat by using combined electrophysiological and anatomical methods. Two
      distinct parietal regions were activated by stimulation of the cerebellar nuclei
      (CN). In the first region located in the depth of the bank of the ansate sulcus,
      stimulation of the CN induced early surface positive-deep negative potentials and
      late surface negative-deep positive potentials. In this cortical area, potentials
      of similar shape and time course were evoked at a shorter latency by stimulation
      of the ventrolateral part of the VA-VL complex where large negative field
      potentials were evoked by stimulation of the CN. After injection of the
      anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in this part of the
      VA-VL complex, axon terminals of thalamocortical (TC) fibers were found in layers
      I, III and IV in the depth of the bank of the ansate sulcus and layers I and III
      in the motor cortex. In the second region located in the suprasylvian gyrus, late
      surface negative-deep positive potentials were evoked by stimulation of the CN
      and similar potentials were evoked at a shorter latency from the dorsomedial part
      of the VA-VL complex where large cerebellar-evoked potentials could be recorded.
      PHA-L injection in this thalamic region stained TC fibers and their terminals in
      layer I of the suprasylvian gyrus, and in layers I and III of the motor cortex.
      The laminar distribution of TC axon terminals in two different regions of the
      parietal cortex could account for the depth profiles of the cerebellar- and the
      thalamic-evoked potentials in each region. These results show that cerebellar
      information is conveyed to two separate areas in the parietal cortex by two
      different TC pathways.

PMID- 1397140
TI  - Neurons of the motor trigeminal nucleus project to the hypoglossal nucleus in the
      rat.
AB  - The hypoglossal nucleus (Mo12) contains motoneurons that innervate the tongue,
      while the motor trigeminal nucleus (Mo5) contains motoneurons that elevate or
      depress the mandible. Previous studies have revealed lateral and medial tegmental
      field neuronal afferents to the Mo12 adjacent to, but not within, the motor
      trigeminal nucleus (Mo5). The current studies demonstrate the presence of
      retrogradely labeled neuronal afferents to the Mo12 within the Mo5 produced by as
      little as 10 nl of Fast Blue (FB) injected into the Mo12. Retrograde labeling of
      Mo5 afferents to the Mo12 with injections of Diamidino Yellow (DY) combined with
      injections of FB into the lumbar spinal cord showed these neuronal afferents to
      the Mo12 are not part of the diffuse projections to motoneurons from the nucleus
      subcoeruleus. Retrograde labeling of Mo5 afferents to the Mo12 with DY combined
      with injections of FB into the masseter revealed these neuronal afferents to the
      Mo12 are not trigeminal motoneurons. These results indicate that Mo5 interneurons
      are part of the lateral tegmental field projections to the Mo12, and are likely
      to comprise part of the neural substrate coordinating the motor activity of the
      jaw and tongue.

PMID- 1397141
TI  - The area postrema is not involved in osmotic activation of neurosecretory cells
      in the supraoptic nucleus.
AB  - Experiments were performed to examine whether or not the area postrema (AP) is
      involved in the osmotic control of neurohypophysial hormone release. In control
      rats and in rats bearing extensive lesions of AP, extracellular action potentials
      were recorded from neurosecretory cells in the supraoptic nucleus (SON) and
      firing rates determined before and after the intraperitoneal (i.p.) injection of
      1.5 M-NaCl solution. Lesion of the AP significantly (p less than or equal to
      0.05, Mann-Whitney's U-test) lowered firing rate of putative vasopressin (phasic)
      cells but not that of oxytocin (non-phasic) cells. In lesioned animals, i.p.
      injection of hypertonic saline, however, caused similar changes in plasma osmotic
      pressure, plasma oxytocin concentration and mean firing rates of both putative
      oxytocin and vasopressin cells to those in control rats. The results suggest that
      the osmotic control of SON neurosecretory cell activity in the rat can take place
      in the absence of the AP.

PMID- 1397142
TI  - Cortex, striatum and cerebellum: control of serial order in a grooming sequence.
AB  - Rats emit grooming actions in sequences that follow characteristic patterns of
      serial order. One of these patterns, a syntactic chain, has a particularly
      stereotyped order that recurs spontaneously during grooming thousands of times
      more often than could occur by chance. Previous studies have shown that
      performance of this sequence is impaired by excitotoxin lesions of the corpus
      striatum. In this study we examined whether the striatum is unique in its
      importance to this behavioral sequence or whether control of the sequence instead
      depends equally upon the cortex and cerebellum. In two experiments, a fine
      grained behavioral analysis compared the effects of striatal ablation to the
      effects of motor cortex ablation, ablation of the entire neocortex, or ablation
      of the cerebellum. Cortical and cerebellar aspiration produced mere temporary
      deficits in grooming sequences, which appeared to reflect a general factor that
      was nonsequential in nature. Only striatal damage produced a permanent sequential
      deficit in the coordination of this syntactic grooming chain. We conclude that
      the striatum has a unique role in the control of behavioral serial order. This
      striatal role may be related to a number of sequential disorders observed in
      human diseases involving the striatum.

PMID- 1397143
TI  - Similarities and differences between cholinergic systems in the superior
      colliculus of guinea pig and rat.
AB  - We studied the distribution of acetylcholinesterase activity and choline
      acetyltransferase immunoreactivity in the superior colliculus of the guinea pig
      and the albino rat, using enzyme histochemical and immunohistochemical methods.
      Choline acetyltransferase-like immunoreactivity was localized in the neuropil
      throughout the colliculi, but the density of the immunoreactive neuropil varied
      among layers as well as between species. In the intermediate collicular layers
      the pattern of choline acetyltransferase immunoreactivity was closely matched by
      the distribution of acetylcholinesterase activity in guinea pig and rat,
      confirming our previous findings in the cat. Furthermore, in the guinea pig, but
      not in the rat, choline acetyltransferase-like immunoreactivity was localized in
      a prominent population of perikarya of the superficial gray layer.

PMID- 1397144
TI  - Supplementary eye field: influence of eye position on neural signals of fixation.
AB  - Single units were recorded in the supplementary eye field of monkeys performing
      visual-oculomotor tasks. Two patterns of unit activity were observed while the
      animals fixated photic stimuli. One consisted of a step in tonic firing frequency
      (either an increase or a decrease, depending on the cell), lasting as long as
      fixation. The occurrence of this pattern did not require the continuous presence
      of a stimulus but the animal had to be provided with an incentive to fixate a
      given location. The other pattern was a monotonically varying firing rate
      dependent on the eye orientation along a particular axis, indicative of eye
      eccentricity in orbit.

PMID- 1397146
TI  - Barbiturate depression of a K+ dependent inhibitory synapse is independent of
      dendritic cable filtering.
AB  - Technical limitations with intracellular electrophysiological methods usually
      restrict recording of postsynaptic potentials only from neuronal soma, a site
      remote from the actual synapse. The intervening dendritic cable interposed
      between the actual synapse and the site of recording can significantly filter the
      synaptic signal. Therefore, investigations of drug effect on synaptic mechanisms,
      based on postsynaptic recordings obtained at the soma, must be interpreted with
      care. The potential role of dendritic cable filtering in the atypical
      pentobarbital depression of a K(+)-dependent inhibitory synapse between the P to
      Nut cell in the posterior packet of the leech was investigated. The effective
      electrical geometry under the conditions of control and 0.5 mM PNB sufficient to
      completely abolish the postsynaptic potential were determined from analyses of
      the membrane charging curves assuming the lumped-soma-short-cable model. Under
      the control condition, the postsynaptic Nut cell exhibits dendritic dominance
      with rho = 2.52, normalized equivalent cable length L = 1.08, and a membrane time
      constant tau o = 52 ms. With phenobarbital application, changes in the
      geometrical parameters consistent with a decrease in the specific membrane
      resistance Rm are observed. Simulation of the drug induced change in the
      electrical geometry demonstrates that the decrease in the post synaptic potential
      is largely due to the decrease in the soma input resistance and an increase in
      the cable filter contributes little to the observed depression of the
      postsynaptic potential. However, the combined effect of the decrease in the input
      resistance and the increase in the cable filtering of synaptic current is
      insufficient in explaining the observed total block of the synaptic potential by
      PNB.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397145
TI  - Longitudinal neuronal organization of defensive reactions in the midbrain
      periaqueductal gray region of the rat.
AB  - In a previous study we investigated the intraspecific defensive reactions evoked
      by excitation of neurons in the intermediate third of the midbrain periaqueductal
      gray matter (PAG) of the rat. Experiments revealed that activation of neurons in
      this region of the PAG mediated: (i) backward defensive behavior, characterized
      by upright postures and backward movements, and (ii) reactive immobility
      ("freezing"), in which the rat remained immobile, but reacted with backward
      defensive behavior to investigative, non-aggressive contact initiated by the
      partner. In the present study, we aimed to extend our understanding of PAG
      mediation of defensive behavior by observing: (i) in a non-aggressive social
      interaction test, the behavioral effects of microinjections of low doses of
      kainic acid (40 pmol in 200 nl) made in the caudal third of the PAG; and (ii) the
      behavioral and cardiovascular effects of microinjections of D,L-homocysteic acid
      (5-10 nmol in 50-100 nl) made in the PAG of the unanesthetized decerebrate rat.
      Kainic acid injections into the area lateral to the midbrain aqueduct in the
      caudal third of the PAG evoked: (i) forward avoidance behavior, characterized by
      forward locomotion and occasional hop/jumps; (ii) reactive immobility
      ("freezing"), in which the rat remained immobile, but reacted with forward
      avoidance behavior to investigative, non-aggressive contact initiated by the
      partner; and (iii) 22-28 kHz ultrasonic vocalizations. These injections also
      evoked a dramatic increase in defensive responsiveness to tactile stimuli on the
      half of the body contralateral, but not ipsilateral, to the site of injection.
      Electroencephalographic measurements indicated that none of these effects were
      secondary to seizure activity. In the decerebrate rat, D,L-homocysteic acid
      injections in the caudal third of the PAG evoked forward running movements along
      with increased blood pressure and heart rate, the strongest effects being evoked
      from the region lateral to the midbrain aqueduct. More rostrally, sites in the
      intermediate PAG evoked backward "defensive" movements, which were also
      associated with increased blood pressure and heart rate.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1397148
TI  - Constancy of motor axon conduction time during growth in rats.
AB  - Axon conduction distance, conduction velocity, and conduction time were measured
      for individual triceps surae motoneurons in Sprague-Dawley rats weighing 230-630
      g (i.e., age range 6-16 weeks). Both conduction distance (nerve length) and
      velocity were closely correlated with weight (r = 0.95 and r = 0.82,
      respectively). In contrast, conduction time did not change as weight increased
      nearly threefold. This striking constancy is probably due to a corresponding
      increase in axon diameter. It could contribute to maintenance of stable motor
      performance during rapid growth.

PMID- 1397147
TI  - Increased expression of GAD mRNA during the chronic epileptic syndrome due to
      intrahippocampal tetanus toxin.
AB  - A few mouse minimum lethal doses (MLD) of tetanus toxin injected into rat
      hippocampus triggers prolonged changes in neuronal function. Spontaneously
      recurring epileptic discharges arise in both the injected and the contralateral,
      uninjected hippocampus. The seizures remit after about 6 weeks, to be succeeded
      by a permanent depression of hippocampal neuronal responses. There is no evidence
      of any loss of pyramidal cells at this low dose of toxin. Here we studied
      presumptive inhibitory, GABAergic neurons, using in situ hybridization (ISH) with
      a probe directed against the mRNA encoding glutamic acid decarboxylase (GAD), at
      each of 1, 2, 4 and 8 weeks after injection of tetanus toxin. Epileptic activity
      was recorded from hippocampal slices prepared from both injected and
      contralateral hippocampi of rats at each time point, unexpectedly persisting
      until 8 weeks. There were no significant differences in the numbers of neurons
      containing GAD mRNA between toxin- and vehicle-injected and control rats in any
      hippocampal subfield, at any survival time, except for an apparently transient
      loss of hilar signal in vehicle-injected rats at 1 and 2 weeks which we attribute
      to a significant, transient loss of neuronal GAD mRNA to below the threshold for
      detection by ISH using this probe. In contrast there was a marked increase in GAD
      mRNA in the toxin-injected group, which reached a peak at 4 weeks, and returned
      to control levels by 8 weeks. The changes were bilateral and were most marked in
      the hilus of the dentate area, but were also significant in CA3 and CA1.
      Upregulation of GAD mRNA was preceded by an increase in the levels of the mRNA
      for the alpha subunit of the GTP binding protein, Gs (Gs alpha), at 2 weeks which
      affected the GABAergic neurons selectively, and not the pyramidal or granule
      cells. These marked changes in GAD mRNA may contribute to putative adaptive
      responses within GABAergic neurons, which would help contain epileptic activity
      in these chronic foci. The changes in GAD expression may be due to mechanisms
      acting through an increase in mRNA encoding Gs alpha.

PMID- 1397149
TI  - Development of parvalbumin immunoreactive neurons in normal and intracranially
      transplanted retinas in the rat.
AB  - Retinas from embryonic day 14 Sprague-Dawley rats were transplanted to the
      midbrain or cerebral cortex of newborn (P0) rats of which the right eye was
      enucleated at the time of transplantation. Parvalbumin immunoreactive (PV-I)
      neurons were studied in the developing retinal transplants, and in the remaining
      retina of the host, as well as in normal retinas. PV-I neurons were identifiable
      in retinas of normal and host rats from postnatal day 5 (P5) onward, with the PV
      I somata primarily in the inner half of the inner nuclear layer and in the
      ganglion cell layer. An adult-like distribution of PV-I neurons was attained at
      P35, as judged by cell packing density, intensity of immunostaining, laminar
      distribution and soma size of subpopulations of PV-I cells. A similar time course
      of development and distribution of PV-I somata was observed in the retinal
      transplants, except for some minor differences such as a slight delay in PV-I
      cells achieving their final distribution. These findings provide evidence that PV
      I neurons can survive, differentiate and mature according to predetermined
      programmes intrinsic to the retinal tissue following transplantation to a new and
      foreign environment.

PMID- 1397150
TI  - Sprouting of fusimotor neurones after partial denervation of the cat soleus
      muscle.
AB  - Normally, gamma motoneurones innervate only the intrafusal fibres of muscle
      spindles. This is a report of sprouting of gamma motoneurones to innervate
      extrafusal muscle fibres following partial denervation of the soleus muscle of
      kittens. In eight newborn animals, the L7 ventral root was cut on one side under
      anaesthesia and the animals were then allowed to recover. At approximately 100
      days of age animals were reanaesthetised and a study made of mechanical
      properties of motor units whose axons ran in the S1 ventral root and supplied the
      partially denervated soleus muscle. Evidence was obtained for sprouting of all
      surviving alpha motoneurones. In addition, in four experiments axons conducting
      within the gamma range, on stimulation, produced measurable tension. In one
      experiment, stimulation of one such gamma axon also produced specific fusimotor
      effects on four afferents identified as coming from primary endings of muscle
      spindles. The gamma axon was therefore a fusimotor axon. The effect observed on
      stimulation of the gamma axon suggested a largely dynamic action. Other examples
      of gamma axons were encountered that on stimulation produced tension, but which
      could not be specifically associated with spindles. In addition, a number of
      gamma axons that did not develop tension were shown, on stimulation, to have
      fusimotor effects that were static in action. It is concluded that in extensively
      denervated muscles gamma motoneurones may sometimes sprout to innervate
      extrafusal fibres. The mechanical properties of the extrafusal fibres innervated
      by such gamma axons were similar to those of ordinary alpha motor units.

PMID- 1397151
TI  - Respiratory network remains functional in a mature guinea pig brainstem isolated
      in vitro.
AB  - We previously developed a perfused isolated brainstem preparation in the adult
      guinea pig (Morin-Surun and Denavit-Saubie 1989a) which permitted us to describe
      several types of rhythmic neuronal discharge. In the present study, we
      demonstrate that nearly all the periodic neuronal activity we recorded in the
      ventral respiratory areas were directly related to the respiratory-like periodic
      output of the hypoglossal nerve. This respiratory-like activity lasted several
      hours only when the brainstem was perfused by the basilar artery. This shows the
      necessity of the intraarterial perfusion to preserve a functional respiratory
      network. Analysis of the characteristics of hypoglossal respiratory-like activity
      shows that (1) two types of respiratory rhythms can be recorded; one with long
      respiratory phases (inspiratory and expiratory) and one with short respiratory
      phases. Depending on the preparation, either type occurs alone or intermingled
      with the other. (2) The shape of the inspiratory-like activity can change
      throughout the recording period while the periodicity remains stable. This
      preparation generates a respiratory rhythm and enables us to dissociate the
      different mechanisms involved in respiratory neurogenesis.

PMID- 1397153
TI  - Development of human precision grip. II. Anticipatory control of isometric forces
      targeted for object's weight.
AB  - The development of anticipatory control during lifts with the precision grip was
      examined in 100 children aged 1 to 15 years and in 15 adults. The children were
      instructed to lift an instrumented test object by using the precision grip
      between the thumb and index finger. The employed grip force, load force (vertical
      lifting force), vertical position and their corresponding time derivatives (i.e.,
      grip and load force rates and acceleration) were recorded. The weight of the
      object was varied between trials to access the influence of the object's weight
      in the previous trial on the isometric force output. Already by the second year,
      children began to use information pertaining to the object's weight in the
      previous lift, i.e., they began to use an anticipatory control strategy. This
      occurred concomitant to the development of mainly bell shaped force rate profiles
      (Forssberg et al. 1991). The succeeding development of a more mature anticipatory
      control was gradual and adult-like capacity was not reached until 8-11 years of
      age.

PMID- 1397152
TI  - Corticofugal actions on lemniscal neurons of the cuneate, gracile and lateral
      cervical nuclei of the cat.
AB  - Extracellular records were made from single identified lemniscal neurons of the
      cell-cluster regions of the cuneate and gracile nuclei, and of the lateral
      cervical nucleus, in pentobarbitone-anaesthetized cats. Forepaw, hind paw or face
      regions of the contralateral Sm I cortex were identified by recording through an
      inserted microelectrode which was then used for stimulation. The effect of a
      double cortical shock or train of shocks was usually inhibition: occasionally
      facilitation was observed, or mixed effects with facilitation preceding
      inhibition. Effects were seen in about half the cells studied in all three
      nuclei. Some cells of the lateral cervical nucleus were strongly excited, an
      effect not seen in the other nuclei. No component of these responses depended on
      suprathreshold stimulus intensities. Some lateral cervical cells were studied
      after deafferentiation by section of the dorsolateral spinal white matter; the
      same pattern of effects was seen. With an upper stimulus limit of 200 microA,
      cuneate but not gracile cells were affected from the cortical forepaw region, and
      gracile but not cuneate cells from the hind paw region. With threshold stimuli in
      an identified part of the forepaw cortical representation it was clear that
      cuneate cells with cutaneous receptive fields in corresponding parts of the
      forepaw had the lowest thresholds (minimum 6 microA). Threshold rose steeply with
      distance across the paw, suggesting quite sharp focusing of corticofugal effects
      in this system. When using similar procedures with the lateral cervical nucleus,
      with an upper limit of 200 microA, stimulation of forelimb cortex, or of facial
      cortex, affected both neurons with forelimb and those with hind limb
      fields.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397154
TI  - Development of human precision grip. III. Integration of visual size cues during
      the programming of isometric forces.
AB  - Recent evidence has shown that visual and haptical size information can be used
      by adults to estimate the weight of the object, forming the basis of the force
      programming during precision grip (Gordon et al. 1991a, b,). The present study
      examined the development of the capacity to use visual size information. In the
      first experiment, 30 children (age 1-7 years) and 10 adults performed a series of
      lifts with two boxes presented in an unpredictable order. The boxes were equal in
      weight but unequal in size and were attached to an instrumented grip handle which
      measured the employed grip force, load force, position and their corresponding
      time derivatives. The isometric force development was not influenced by the box
      size before the age of 3. However, the children aged 3 years and older
      demonstrated greater visual influences on the force programming than adults. To
      determine more precisely when children began to use visual size information, a
      second experiment in which the size and weight covaried was performed on 15
      children. Children still did not use the size information during the force
      programming until the later half of the third year. It is concluded that this
      ability, probably involving associative transformations between the size and
      weight of objects, emerges around one year after anticipatory control based on
      somatosensory information pertaining to the weight of the object.

PMID- 1397155
TI  - Phase-dependent reversal of reflexly induced movements during human gait.
AB  - To investigate whether phase-dependent reversals in reflex responses on
      electromyography (EMG) are accompanied by movement reversals, a series of human
      volunteers were studied for their behavioural responses to sural nerve
      stimulation during running or walking on a treadmill. Low-intensity stimulation
      (less than 2.5 x perception threshold, T) of the sural nerve yielded facilitatory
      responses in the tibialis anterior muscle (TA), correlated with an induced ankle
      dorsiflexion (mean maximum 4 degrees) in early swing. The same stimuli yielded
      primarily TA suppression and weak ankle plantar flexion (mean maximum 1 degree)
      at end swing. The correlated induced knee angle changes did not precede the ankle
      changes, and they were relatively small. Mean maximum flexion in early swing was
      6.2 degrees, while mean maximum extension was 3.7 degrees. High-intensity
      stimulation of the sural nerve (greater than 2.5 x T) always gave rise to
      suppression of the ongoing activity. This resulted in a second type of movement
      reversal. During late stance and early swing the responses in TA were suppressive
      (i.e. below background activity) and related to ankle plantar flexion. In
      contrast, the responses during early and middle stance consisted of suppression
      in extensor activity (gastrocnemius medialis and soleus) and ankle dorsiflexion.
      The data are discussed in terms of a new hypothesis, which states that the
      responses to electrical stimulation of cutaneous nerves during locomotion do not
      correspond directly to corrections for stumbling following mechanical
      perturbations during the step cycle. Instead, the data invite a reinterpretation
      in terms of the opening and closing of reflex pathways, presumably by a central
      pattern generator for locomotion.

PMID- 1397156
TI  - The control of arm pointing movements in three dimensions.
AB  - In this study we investigated pointing movements made with an extended arm.
      Despite the large number of mechanical degrees of freedom, limb orientation
      adopted during pointing could be described by rotation axes contained on a two
      dimensional curved surface. As a result of the curvature, the orientation of a
      linear plane approximating a small region of the curved surface was dependent on
      the location of the movements within the full workspace. These results account
      for earlier suggestions that limb orientation could be described by coplanar
      rotation vectors and that the orientation of the plane moved with the workspace.
      Despite the additional complexity, our results indicate that the number of
      degrees of freedom used to position the extended forearm is reduced from four to
      two for normal pointing movements. Contributions to orientation of the wrist and
      hand by supination/pronation of the forearm were minor for changes in shoulder
      yaw angle. However, supination/pronation added significantly to orientation of
      the hand for changes in shoulder pitch angle.

PMID- 1397157
TI  - Motor strategies in landing from a jump: the role of skill in task execution.
AB  - A motor performance which involves multijoint coordination and belongs to the
      natural repertoire of motor behavior has been studied. Displacements have been
      related to EMG in the lower limb when taking off and landing from a jump down (45
      cm) onto two surfaces of differing compliance in two populations of teenage
      girls: skilled and unskilled. To evaluate the performance, an index was defined
      taking into account: 1) the time required for reaching stability (1 body weight)
      after landing, and 2) the amount of sway during the stabilization time. Despite
      the apparent intra and inter subject similarities in performing the jump-down,
      slight differences were observed in both the kinematics and electromyogram
      patterns. During takeoff, two strategies were identified that were not related to
      either skill or landing surface compliance. The most common strategy, "Push Off",
      is characterized by almost full joint extension when departing from the jump
      platform and includes a swing period during flight. The other strategy, "Roll
      Off", is characterized by joint flexion at departure and continual extension
      during midflight. While the ankle dorsiflexor, tibialis anterior, is active in
      preparation for the takeoff phase in both strategies, it is followed by
      activation of the ankle plantarflexors, lateral gastrocnemious and soleus and the
      hip/knee musculature, rectus femoris, biceps femoris, and vastus lateralis, only
      in the push off strategy. The roll off strategy is characterized by a lack of
      other muscle activation prior to takeoff. At landing, regardless of the strategy
      used in takeoff, onset of muscles followed the same sequence for both landing
      surfaces; ankle musculature activity began first followed by activity in the knee
      and hip musculature. The onset of the musculature occurred closer to landing when
      landing on the more compliant surface. Skilled subjects were characterized by
      adjustments in amount of ankle extension present at landing and concomitant
      flexion post-landing with respect to landing surface. When landing on the rigid
      surface, the ankle was more plantarflexed and onset of the dorsiflexor occurred
      after that of the plantarflexors; on foam, dorsiflexor activity was coincident
      with the plantarflexors. Ankle joint range of motion post-landing was
      subsequently larger when landing on the rigid surface. In contrast, unskilled
      individuals used a default strategy for landing on both surfaces where the ankle
      position and movement was between that seen for the two conditions in the skilled
      individual. It is suggested the landing and takeoff phases are programmed
      independently in both skilled and unskilled subjects.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1397158
TI  - cFos labeling in rat superior colliculus: activation by normal retinal pathways
      and pathways from intracranial retinal transplants.
AB  - Previous studies in this laboratory have shown that intracranial retinal
      transplants can establish both anatomical and functional connections with the
      host brain. Embryonic rat retinae transplanted intracranially into neonatal host
      brains are capable of evoking appropriate physiological and behavioral responses
      when illuminated. The present study employs the specific expression of the cFos
      protein to identify brain regions in which immediate-early gene activation can be
      recognized in response to flash stimuli delivered to retinal transplants and to
      normal intact retinae. Stimulation of the intact eye induced significant cFos
      expression in various visual centers, including the stratum griseum superficiale
      of the superior colliculus and the pretectal area, but not in the dLGN,
      suprachiasmatic nucleus, or retina. Animals with functional transplants expressed
      cFos throughout the depth of the stratum griseum superficiale and stratum opticum
      of the superior colliculus, thus apparently activating an additional population
      of superior collicular cells. Like the eye-stimulated animals, animals with
      functional transplants failed to elicit significant cFos expression in the dLGN
      or transplanted retina. This study indicates that intracranial retinal
      transplants are capable of forming functional connections with the host superior
      colliculus which not only mediate transient changes in electrical activity but
      also may affect gene expression through the induction of the c-fos gene.

PMID- 1397159
TI  - Immunohistochemical changes of neuronal calcium-binding proteins parvalbumin and
      calbindin-D-28k following unilateral deafferentation in the rat visual system.
AB  - The neuron-specific calcium-binding proteins, parvalbumin and calbindin-D-28k,
      were studied in the subcortical visual system of normal and unilaterally
      deafferented albino rats. Immunohistochemistry with monoclonal antibodies was
      used on vibratome sections through optic tract (OT), dorsal lateral geniculate
      nucleus (dLGN), olivary pretectal nucleus (OPN), and superior colliculus (SC). In
      controls, OT stained strongly for parvalbumin and weakly for calbindin-D-28k. The
      dLGN contained a plexus of parvalbumin-positive fibers. In dLGN, calbindin-D-28k
      antibodies showed strong labeling of some neurons with long dendrites and weak
      staining of the cytoplasm in other neurons. In OPN, parvalbumin stained a ring of
      neurons and terminals in the shell region, whereas calbindin-D-28k was contained
      in medial cell populations. In SC, parvalbumin was contained in fibers,
      terminals, and neurons throughout the visual layer. Calbindin-D-28k showed a
      laminar distribution of neurons with a predominance in deep portions of
      superficial grey matter and in ventral portions of stratum opticum. Following
      unilateral deafferentation induced by optic nerve section, retinal axons showed
      immunohistochemical changes related to Wallerian degeneration and target neurons
      reacted by changes of calcium-binding proteins. Parvalbumin and calbindin-D-28k
      immunostaining decreased during Wallerian degeneration of OT. In the deafferented
      dLGN, immunohistochemical labeling for calbindin-D-28k declined in strongly
      stained neurons from 4 to 21 days after lesion. Measurement of dendritic length
      per number of cells or per area of dLGN showed a significant decline for the
      contralateral side at 4, 8, and 21 days (ANOVA, P less than 0.05). In
      deafferented OPN, terminal-like staining for parvalbumin decreased and neuronal
      labeling was enhanced. In deafferented SC, the neuronal and dendritic staining
      for parvalbumin increased beginning from Day 1 on and persisting at Day 21,
      whereas fibers and terminal-like elements decreased in staining. Measurement of
      parvalbumin-positive neurons per area of SC showed a significant increase of
      labeling in the contralateral side from Day 1 to Day 21 (ANOVA, P less than
      0.05). These studies show that cellular responses to deafferentation of visual
      neurons involve a regulation of calcium-binding proteins. The decline in staining
      for calbindin-D-28k in dLGN may relate to reduced retinal afferent activity. The
      progressive cellular changes in parvalbumin staining may be related to unmasking
      of intrinsic neurons after removal of parvalbumin-containing, afferent fibers and
      terminals. Additionally, the changes of parvalbumin labeling in SC neurons may
      reflect a plastic reorganization of local circuits known to occur in rat SC in
      response to deafferentation.

PMID- 1397160
TI  - Observation of the blood-brain barrier function and vasomotor response in rat
      microcirculation using intravital fluorescence microscopy.
AB  - The blood-brain barrier function and the vasomotor response in rat
      microcirculation was studied using a closed cranial window technique and an
      intravital fluorescence microscope with an attempt to reduce both the light
      intensity and the amount of 2% Na(+)-fluorescein to as little as possible. The
      light intensities in the focus were less than or equal to 2.5 mW/cm2, and with
      the low-light TV camera we were able to reduce the total amount of the dye to
      less than or equal to 0.7 ml during 6-h experiments. Observing the brain surface
      every 30 min showed that the barrier function remained intact for up to 6.0 h
      following the first iv administration of the dye. This study has reconfirmed that
      the pial vessels have physiological vasomotor responses (e.g., CO2 reactivity).
      The osmotic barrier disruption started at a small venule 10 min after the start
      of superfusion with mannitol (1000 mOsm/liter). In conclusion, the microscope
      system and the small animal model used in this study were useful in studying the
      blood-brain barrier function and the vasomotor response simultaneously under
      various experimental conditions.

PMID- 1397162
TI  - Extracellular proteins of goldfish optic tectum labeled by intraocular injection
      of 3H-proline.
AB  - A prominent group of soluble glycoproteins with a molecular weight of 30K-40K and
      pI 5.0-5.6 was detected in various parts of the goldfish brain as well as in the
      optic nerves. Since these proteins are readily liberated from the tissue, we have
      designated them exoglycoproteins (X-GPs). The X-GPs in the optic tectum were
      found to be labeled after intraocular injection of radioactive tracers, in a
      manner consistent with the labeling of proteins transported in the optic axons.
      However, the labeling of X-GPs was blocked by intracranial injection of a protein
      synthesis inhibitor, whereas the labeling of axonally transported proteins was
      unaffected. This shows that the X-GPs can be synthesized locally within the
      brain. Nevertheless, when protein synthesis in the retina was blocked, the
      labeling of the X-GPs in the tectum was prevented, like the labeling of axonally
      transported proteins. Thus precursors for the synthesis of X-GPs can be derived
      from materials transported in the optic axons. This synthesis can occur in
      nonneuronal cells, as indicated by the incorporation of labeled amino acid into X
      GPs in optic nerves directly exposed to the label. The synthesis of X-GPs was
      increased in regenerating nerves, suggesting that these proteins may play a role
      in regeneration. Partial amino acid sequencing of the proteins showed that they
      are identical to the proteins previously identified as "ependymins," which have
      been implicated in neuronal plasticity. There are minor differences in amino acid
      sequence among some individual spots.

PMID- 1397161
TI  - Alteration of second-messenger ligand binding following 2-hr hemispheric ischemia
      in the gerbil brain.
AB  - The alterations of second-messenger ligand binding and cerebral blood flow (CBF)
      were evaluated in the gerbil brain after 2-h unilateral common carotid artery
      occlusion. [3H]Forskolin (FK) and [3H]phorbol-12,13-dibutyrate (PDBu) were used
      as specific ligands for adenylate cyclase (AC) and protein kinase C (PKC)
      activity estimation, respectively. CBF was determined at the end of the
      experiment by the [14C]iodoantipyrine method. A quantitative autoradiographic
      method permitted simultaneous measurement of the three parameters in the same
      brain. The levels in the caudate-putamen, globus pallidus, and hippocampus were
      analyzed. The animals were divided into three groups: Group 1 with severe
      ischemia (CBF in the lateral nuclei of the thalamus (CBFt) less than 50 ml/100
      g/min), Group 2 with mild ischemia (CBFt greater than or equal to 50 ml/100
      g/min), and the Sham Group. The PDBu binding revealed a statistically significant
      increase in the caudate-putamen, lateral nuclei of the thalamus and hippocampus
      (CA1 and CA3 regions and dentate gyrus) on the ischemic side in Group 1 as
      compared to that in Group 2 and the Sham Group. In contrast, the FK binding did
      not show any significant changes in any of the regions. These data and our
      previous findings for 6-h ischemia suggest that (1) PKC translocation to the cell
      membrane may occur at the early ischemic phase in particular regions including
      the caudate-putamen, lateral nuclei of the thalamus and hippocampus, with the
      translocated PKC gradually diminishing during the subsequent ischemic period; and
      (2) the suppression of the AC system observed in 6-h ischemia may not appear in
      the early ischemic phase.

PMID- 1397163
TI  - Quisqualic acid-induced lesion of the nucleus basalis of Meynert in young and
      aging rats: plasticity of surviving NGF receptor-positive cholinergic neurons.
AB  - Previous studies have demonstrated that cholinergic neurons in the adult rat
      forebrain, i.e., septal region, are able to respond and regenerate after damage
      followed by exogenous treatment with beta-nerve growth factor. Furthermore, it
      has been shown that an age-related loss of NGF-receptor (NGFr) immunoreactivity
      occurs in cholinergic septal neurons. Since the regenerative capacity of
      cholinergic neurons is of importance for potential therapeutic strategies during
      the course of age-related neurodegenerative diseases, we have compared NGFr
      positive neurons in young adult (3 months old) and in aging (18-24 months old)
      rats in their ability to produce a physiological plasticity response after
      surviving an excitotoxic lesion of the nucleus basalis of Meynert (NBM). In aging
      control rats, NGFr immunoreactivity within NBM neurons was significantly reduced,
      in analogy to data obtained earlier from studies about septal neurons in aged
      rats. After lesion with quisqualic acid, a severe cell loss as well as atrophy of
      remaining cholinergic neurons was observed in both groups. Investigation of the
      NBM at various times after the lesion demonstrated signs of axonal or dendritic
      sprouting and local regeneration, with a maximum seen 3 months after the lesion.
      No age-related differences in the response could be found. However, despite local
      fiber growth, no reinnervation of the frontal and parietal cortex could be noted,
      as demonstrated by acetylcholinesterase histochemistry. Our findings suggest
      that, despite a relatively early onset of NGFr decline during lifetime,
      cholinergic cells keep the capacity for a plastic response, although they
      ultimately fail to reinnervate the neocortex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397164
TI  - Spreading depression induces prolonged reduction of cortical blood flow
      reactivity in the rat.
AB  - The purpose of the present study was to examine the dynamic aspects of the
      cerebrovascular events occurring during and up to 2 h following cortical
      spreading depression (CSD) in the rat, using the mass spectrometry technique
      which enables continuous measurements of the cortical tissue PO2 and PCO2 and
      repeated blood flow measurements (CoBF) by helium clearance. We mostly sought to
      determine whether cortical perforation by a stimulation electrode induced long
      lasting perturbation of the cortical vasoreactivity to hypercapnia and basal
      forebrain electrical stimulation. Cortical perforation in the animal under alpha
      chloralose anesthesia, chronically implanted with mass spectrometry probes, was
      associated with biphasic changes in tissue gases. PO2 first briefly decreased (
      7.8%) and then strongly increased (+79%) while PCO2 changed in the opposite
      direction (+7%, -13%) in the ipsilateral frontal cortex. Qualitatively similar
      changes occurred in the ipsilateral parietal cortex. The CoBF measurements showed
      a marked vasodilation (131 and 108% in the frontal and parietal cortex,
      respectively) in parallel with the PO2 increase, followed by a prolonged (60
      min), moderate hypoperfusion (maximum -17% at 20 min after CSD). There was a
      pronounced reduction of vascular reactivity to both hypercapnia (20.3% of the
      control response) and substantia innominata stimulation (1/6 of the response
      obtained 80 min later) at 10 min after CSD. Both reactivities progressively
      recovered in approximately 2 h. Since the issue of CSD in human has become a
      popular hypothesis for migraine, the reduced cerebrovascular reactivity could
      constitute the basis of a test for the involvement of CSD in migraine.

PMID- 1397165
TI  - Forelimb motor performance following cervical spinal cord contusion injury in the
      rat.
AB  - The purpose of this study was to examine the degree, persistence, and nature of
      forelimb behavioral deficits following cervical spinal cord contusion injury in
      the rat. Forelimb reaching and pellet retrieval, forehead adhesive sticker
      removal, and vibrissae-induced forelimb placing were examined for 16 weeks
      following a weight-drop injury (10.0 g-2.5 cm) at the C4-C5 spinal level. Nine of
      13 rats studied were unable to perform the pellet retrieval task due to
      pronounced forelimb extension hypometria. However, these animals did carry out
      the forehead sticker removal and vibrissae-induced placing tasks. Therefore, the
      loss of reaching ability related to pellet retrieval was not due to generalized
      paralysis. This interpretation was further supported by evaluation of the
      rostrocaudal extent of relative motoneuron loss from 1-mm divisions through the
      lesion zone. The extent of motoneuron pathology ranged from 2 to 6 mm but was
      largely confined to the C4-C5 spinal segments. Morphometric assessments of axonal
      sparing revealed that pellet retrieval performance during the last month of
      observation was significantly correlated with fiber sparing in the dorsal columns
      and ventral white matter, whereas no significant correlation could be
      demonstrated with regard to dorsolateral white matter. While there were no
      conspicuous differences in qualitative assessments of damage to interneuron pools
      (i.e., laminae V to VII) between the nonreaching and retrieval-recovered rats,
      the possibility of combined white and gray matter pathology contributing to this
      deficit still exists. These initial findings thus demonstrate that the weight
      drop contusion injury model can be adopted to studies of cervical spinal cord
      trauma in the rat. Such lesions yield permanent deficits in forelimb function
      lending to future studies of possible therapeutic interventions. Furthermore,
      performance deficits observed at 1 week postinjury in the placing and forehead
      sticker removal tasks can be predictive of any potential for long-range
      spontaneous recovery in pellet retrieval ability.

PMID- 1397166
TI  - Axonal conduction and electrical coupling in regenerating earthworm giant axons.
AB  - Severed halves of medial giant axons (MGAs) and lateral giant axons (LGAs) in
      earthworms survive and are functionally reconnected as early as the first
      postoperative week. During the first 150 postoperative days, there is an increase
      in conduction velocity of action potentials and strength of electrotonic coupling
      between the severed axonal stumps across the lesion site. Electrophysiological
      analyses suggest that this functional reconnection occurs by transmission of
      action potentials through the lesion site by active propagation along neurites
      which make electrotonic connections rather than chemical synapses. The
      regenerated connections restore the original connectivity pattern for conduction
      of action potentials or spread of electrotonic potentials; i.e., MGA stumps
      reconnect with MGA stumps, and LGA stumps with LGA stumps. These and other data
      suggest that the mechanisms responsible for establishing appropriate functional
      reconnection of severed earthworm giant axons requires cell-specific matching of
      axons and neurites, rather than a competition between appropriate and
      inappropriate functional connections.

PMID- 1397167
TI  - Restoration of orbicularis oculi function by contralateral orbicularis oculi
      innervated muscle flap vs neuromuscular pedicle technique.
AB  - In preliminary experiments with dogs and cats, unilateral paralysis of the
      orbicularis oculi muscle group was produced by a section of the seventh nerve
      that included the posterior auricular branch. Either one of two procedures was
      then employed in attempts to reinnervate the paralyzed eyelid. In one group of
      animals, a neuromuscular pedicle was employed and in another, a contralateral
      orbicularis innervated muscle flap was used. Both methods restored synchronous,
      reflex blinking to the denervated eyelid. Of the two procedures, neurotization
      appears to offer the greater promise because the use of a neuromuscular pedicle
      requires an expendable nerve that is functional, and no such suitable substitute
      is available in humans.

PMID- 1397168
TI  - Long-latency auditory-evoked potentials: role of polysensory association cortex
      in the cat.
AB  - The objective of this study has been to define the role of polysensory
      association cortex in the generation of "wave NA" and of "wave C," long-latency
      auditory-evoked potentials recorded from the vertex of conscious cats as,
      respectively, a marked negative potential of latency 30-48 msec followed by a
      broad positive wave of latency 50-75 msec. Wave C may represent the feline
      analogue of the longer latency human auditory-evoked potential wave P2, insofar
      as both waveforms are very large amplitude, long duration positivities
      characterized by long recovery cycles. Based on previous studies of wave C and
      the generators of other middle-latency evoked potentials, we hypothesized that
      both wave NA and wave C might reflect, at least in part, the cortical culmination
      of a nonlemniscal line auditory association system arising in reticulothalamic
      projections to intralaminar and associated ventral thalamic regions. Relays from
      these thalamic areas are known to project to polysensory association cortex,
      including pericruciate gyrus, anterolateral gyrus, and medial suprasylvian gyrus.
      Therefore we implemented a series of lesion experiments to characterize the role
      of each of these cortical areas in the production of wave NA and wave C. Our
      results indicate that all three polysensory association areas contribute
      significantly to both waves NA and C, although the largest effects followed
      ablation of the pericruciate area alone. Thus, the generator substrates of waves
      NA and C appear to involve a long-recovery cycle system which functionally
      incorporates activation of association cortex.

PMID- 1397169
TI  - Threshold relationship between cerebral blood flow, glucose utilization, and
      energy metabolites during development of stroke in gerbils.
AB  - Focal brain ischemia was produced in halothane-anesthetized Mongolian gerbils by
      occluding the right common and the left external carotid artery. Ninety minutes
      after vascular occlusion the following regional hemodynamic and metabolic
      parameters were evaluated in adjacent cryostat sections taken from seven
      different coronal planes of each brain: cerebral blood flow (CBF), glucose
      utilization (CMRG), and the tissue content of ATP and glucose. NADH fluorescence
      was recorded from the surface of the cryostat block. In addition, tissue slices
      were taken from each brain to determine the rate of phosphorylation of 2
      deoxyglucose in ischemic and nonischemic regions. Depending on the density of
      ischemia, the following metabolic disturbances were observed. At CBF values below
      35 ml x 100 g-1 x min-1 CMRG increased and at values below 25 ml x 100 g-1 x min
      1 it declined sharply. Glucose content declined when CBF was below 35 ml x 100 g
      1 x min-1 and ATP fell at CBF below 20 ml x 100 g-1 x min-1. At 10 ml x 100 g-1 x
      min-1 ATP was completely depleted. NADH fluorescence was found elevated at flow
      rates that caused an increase of glucose utilization and was maximal when CBF
      stopped. The ischemic thresholds for the initial increase in CMRG and the
      complete depletion of ATP content represent the metabolic equivalent of the
      penumbra zone and provide a basis for the evaluation of therapeutic procedures
      for the treatment of stroke.

PMID- 1397170
TI  - MR imaging for measurements of ventricles and cerebral cortex in postnatal rats
      (H-Tx strain) with progressive inherited hydrocephalus.
AB  - As part of a wider investigation on brain structure and function in young rats
      with inherited hydrocephalus, this study was undertaken to develop a technique to
      monitor, and quantify, progressive changes in ventricle and cortical dimensions
      in hydrocephalic rats in vivo. Magnetic resonance images were obtained with a T1
      weighted protocol and a multislice variant of the inversion recovery sequence
      which displayed optimal contrast between cerebrospinal fluid and brain
      parenchyma. Rats were imaged at 7, 14, and 21 days after birth by taking 10
      contiguous 2.0-mm coronal slices. Area and distance measurements were taken from
      the displayed images, enabling calculation of ventricle volumes, cortical length,
      and cortical thickness. The lateral ventricle volume, which was already 100-fold
      larger than control at 7 days, increased to over 1000 mm3 at 21 days. The
      anterior-posterior length of the cortex was up to 27% larger in hydrocephalics
      and the cortical mantle was up to 75% thinner, particularly in the posterior
      cortex. Subsequent fixation and histological sectioning of two 21-day-old rats
      showed that the smaller dimensions, which were obtained from analysis of the
      sections, could be accounted for by shrinkage of the tissue during dehydration
      and wax embedding.

PMID- 1397171
TI  - Disappearance of astrocytes and invasion of macrophages following crush injury of
      adult rodent optic nerves: implications for regeneration.
AB  - Injury to the mammalian central nervous system results in loss of function
      because of its inability to regenerate. It has been postulated that some axons in
      the mammalian central nervous system have the ability to regenerate but fail to
      do so because of the inhospitable nature of surrounding glial cells. For example,
      mature oligodendrocytes were shown to inhibit axonal growth, and astrocytes were
      shown to form scar tissue that is nonsupportive for growth. In the present study
      we report an additional phenomenon which might explain the failure of axons to
      elongate across the site of the injury, namely, the absence of astrocytes from
      the crush site between the glial scar and the distal stump. Astrocytes began to
      disappear from the injury site as early as 2 days after the injury. After 1 week
      the site was necrotic and contained very few glial cells and numerous
      macrophages. Disappearance of glial cells was demonstrated in both rabbit and rat
      optic nerves by light microscopy, using antibodies directed against glial
      fibrillary acidic protein, and by transmission electron microscopy. Results are
      discussed with reference to possible implications of the long-lasting absence of
      astrocytes from the injury site, especially in view of the differences between
      the present findings in rodents and our recent observations in fish.

PMID- 1397172
TI  - Magnetic resonance imaging to monitor pathology of caudate-putamen after
      excitotoxin-induced neuronal loss in the nonhuman primate brain.
AB  - We used MR imaging to locate and monitor in vivo the pathological events taking
      place 2 to 4 weeks after unilateral striatal injections of ibotenic acid (IA) in
      the Papio papio baboon. As early as 2 weeks after IA injections, excitotoxic
      lesions in the caudate and the putamen were directly visualized on T1-weighted
      images as small areas of low signal intensity. On T2-weighted images, the lesion
      sites were visualized as areas of high-intensity signal, spreading over larger
      areas than the corresponding regions in T1-weighted images. These alterations of
      T2-values in the lesioned striatum persisted 4 weeks after surgery. However, as
      the striatal degeneration progressed from 2 to 4 weeks after lesion, the size of
      the areas of high signal intensity on T2-weighted images decreased, whereas the
      same regions appeared essentially unmodified on T1-weighted images. A marked
      enlargement of the ipsilateral lateral ventricle (a characteristic of excitotoxic
      striatal lesions) could be detected 4 weeks after surgery, on both axial T1- and
      T2-weighted images. Comparisons of MR images with postmortem anatomical data
      indicated that areas of increased T1 values corresponded to regions of severe
      neuronal depletion (a direct result of the excitotoxic lesion), whereas areas of
      increased T2 values corresponded to regions of increased content in astrocytes
      and ferritin and probably in the early period following lesion (2 weeks) to a
      superimposed edema.

PMID- 1397173
TI  - Effects of adrenal medulla grafts on plasma catecholamines and rotational
      behavior.
AB  - The mechanisms by which adrenal medulla grafts influence the function of host
      brains in animal models of Parkinson's disease are unclear. To explore this
      issue, fragments of adrenal medulla or sciatic nerve were transplanted into the
      lateral ventricle of bilaterally adrenalectomized (ADX) or sham-ADX rats with
      unilateral 6-hydroxydopamine lesions of the substantia nigra. Additional control
      group received sham-transplantation surgery. Behavioral effects of these
      procedures were tested following administration of apomorphine, amphetamine, or
      nicotine. Plasma catecholamines were measured before and after transplantation
      surgery. In both ADX and sham-ADX rats, adrenal medulla grafts produced greater
      decreases in apomorphine-induced rotational behavior than did sciatic nerve
      grafts or sham-transplanted groups. Decreases in rotation were smaller in ADX
      than in sham-ADX animals, regardless of graft treatment. Plasma catecholamines
      increased after transplantation surgery in each of the sham-ADX groups,
      regardless of graft type. Increases in plasma dopamine concentrations were
      associated with decreases in rotational behavior. Five months after
      transplantation, grafted chromaffin cells demonstrated catecholamine
      fluorescence, tyrosine hydroxylase (TH) and chromogranin A immunoreactivities,
      and expression of TH mRNA. It is concluded that adrenal medulla grafts produce
      decreases in apomorphine-induced rotation through a combination of two
      independent effects. One is a specific effect of adrenal medulla grafts. The
      second is a nonspecific effect that requires an intact adrenal gland and may be
      related to increases in plasma catecholamine concentrations.

PMID- 1397174
TI  - Basic fibroblast growth factor prevents neuronal death and atrophy of
      retrogradely labeled preganglionic neurons in vivo.
AB  - We have used retrograde fluorescent tracing (fast blue) both before (prelabeling)
      and at time points after selective unilateral adrenomedullectomy in vivo (post
      labeling) in order to investigate the survival and morphology of sympathoadrenal
      preganglionic (SAP) neurons located in the lower thoracic intermediolateral (IML)
      cell column of the adult rat spinal cord. By prelabeling with fast blue it was
      found that the majority (i.e., more than 85%) of the SAP neurons underwent
      degeneration and were lost from the IML cell column within 4 weeks after
      peripheral target lesion and administration of intramedullary gelfoam implants
      containing a nontrophic control protein cytochrome c. By contrast, atrophy and
      loss of SAP neurons was largely prevented by local treatment (intramedullary
      implants) with recombinant basic fibroblast growth factor (bFGF) as determined
      from counts of large and "healthy-looking" prelabeled neurons within the IML
      column ipsilateral to the lesioned (i.e., operated) side 4 weeks
      postimplantation. The time course of withdrawal of preganglionic axons from their
      lesioned target area was investigated by fast blue injections into intramedullary
      (control or bFGF) implants at weekly intervals postimplantation (postlabeling)
      and was documented by counting the number of healthy SAP neurons that retained
      the label. Without bFGF treatment, progressive numerical loss of SAP neurons was
      evident within 1 to 4 weeks postlesioning, indicative of pronounced retrograde
      cell degeneration. Retrograde cell degeneration was insignificant during the
      first 2 weeks postimplantation after early postlesion treatment with exogenous
      bFGF; it was apparently postponed to occur after 1 month. Implantation of gelfoam
      containing neutralizing anti-bFGF-antibodies resulted in accelerated retrograde
      axon degeneration implying that bFGF is an endogenous trophic factor for SAP
      neurons. The results are consistent with the idea that SAP neurons actually die
      following peripheral target lesion and are not supported from other trophic
      sources. However, these neurons can be prevented from disconnection-induced death
      by providing exogenous bFGF. Limited amounts of endogenous FGF may also become
      available to SAP axons by disintegration of nerve terminal-surrounding cells
      delaying the process of retrograde SAP neuron death.

PMID- 1397175
TI  - Neurotrophic effects of steroids on lesion-induced growth in the hippocampus. II.
      Hormone replacement.
AB  - The mediation of lesion-induced sprouting in the nervous system is a complex
      interaction of local membrane factors and circulating hormones. This series of
      studies examines the reactivity of the sprouting response of both male and female
      subjects under different hormonal conditions. Young adult male and female Sprague
      Dawley rats which were gonadectomized (GDX) and adrenalectomized (ADX) underwent
      a unilateral entorhinal cortex lesion, which partially denervates the molecular
      layer of the ipsilateral hippocampal denate gyrus. At the time of the lesion,
      each animal received hormonal therapy. Fifteen days post-ERC-ablation the brains
      were analyzed for changes in reactive fiber outgrowth in the hippocampal
      commissural/associational afferents. Fiber outgrowth in females in the
      "asteroidal" (GDX/ADX) condition was unaffected. Asteroidal males demonstrated a
      decreased response. Gonadal steroid replacement, estrogen or testosterone,
      enhanced outgrowth in both asteroidal males and females. Glucocorticoid
      replacement suppressed outgrowth in both asteroidal males and females. Gonadal
      steroids clearly have neurotrophic activity which is interactive with
      glucocorticoid activity. Glucocorticoids under the GDX/ADX conditions in vivo
      have a negative impact on fiber outgrowth in both sexes. The effect of
      glucocorticoids is most dramatic when compared to the outgrowth of asteroidal
      animals without additional hormonal supplementation.

PMID- 1397176
TI  - Myelinated fiber regeneration after sciatic nerve crush: morphometric
      observations in young adult and aging mice and the effects of macrophage
      suppression and conditioning lesions.
AB  - To study myelinated nerve fiber regeneration during aging, the right sciatic
      nerves of 6- and 24-month-old mice were crushed at the sciatic notch. Two, 4, and
      8 weeks later, both groups of mice were perfused. The sciatic nerves were
      processed so that the transverse sections of each nerve subsequently studied by
      light and electron microscopy included the entire posterior tibial fascicle 5 mm
      distal to the crush site. Two weeks after axotomy, fascicles of aging mice
      contained significantly fewer regenerated myelinated fibers than those of young
      adults. After 4 weeks, the difference in the number of myelinated fibers was
      less. However, measurements of myelinated fibers in fascicles of aging mice
      showed that areas of Schwann cell cytoplasm and myelin were significantly reduced
      at all intervals. In contrast, although axon diameters in aging mice were
      somewhat less 2 weeks after crushing, the difference decreased with time,
      suggesting that in nerves of aging mice, regenerative responses of Schwann cells
      were more affected than those of axons. Other experiments in young mice showed
      that myelinated fiber regeneration could be retarded by suppressing macrophage
      responses and was not significantly changed by conditioning lesions before crush
      injury.

PMID- 1397177
TI  - Divergent effects of astroglial and microglial secretions on neuron growth and
      survival.
AB  - Brain glia have a secretory capacity which can modulate neuronal function.
      Astrocytes release proteins which enhance neuronal survival and induce neuronal
      growth and differentiation. These effects can be blocked by antagonists of
      voltage-dependent calcium channels and may be partly mimicked by Bay K 8644, a
      calcium channel agonist. Two of these neurotrophic proteins appear, on the basis
      of their physical properties and effects on ciliary ganglion neurons, to be
      ciliary neurotrophic factor and basic fibroblast growth factor. Activated
      microglia release a heat- and protease-stable neurotoxin of low molecular weight.
      This neurotoxicity is blocked by NMDA receptor antagonists. Ciliary neurons
      exposed to the microglial neurotoxin exhibit an abnormal distribution of
      neurofilament immunoreactivity, which becomes concentrated in a perinuclear
      region, while the astroglial growth factors induce neurofilament organization
      into an extensive neuritic network. The astrocyte-released growth factors can
      counteract the effect of the microglial neurotoxin and lead to unimpaired neural
      differentiation in the presence of the neurotoxin.

PMID- 1397178
TI  - Human fetal xenografts of brainstem tissue containing locus coeruleus neurons:
      functional and structural studies of intraocular grafts in athymic nude rats.
AB  - Fetal human brainstem tissue including the nucleus locus coeruleus was
      transplanted to the anterior eye chamber of athymic nude rats. Most transplants
      survived and grew in the anterior chamber of the eye. After 9-15 months, the host
      animals were anesthetized and electrophysiological or in vivo electrochemical
      recordings were performed. The brainstem transplants contained spontaneously
      active neurons with regular single-spike firing patterns. The neurons responded
      to ipsilateral light stimulation with an increase in firing rate and to the alpha
      2-receptor agonist clonidine with significantly decreased firing rates. In vivo
      electrochemical studies demonstrated reproducible noradrenergic overflow after
      local application of potassium. Immunohistochemical evaluation of the brainstem
      transplants showed an abundance of tyrosine hydroxylase-positive neurons and
      neurites in all transplants and a dense network of neurofilament-, synapsin-, and
      glial fibrillary acidic protein-positive profiles throughout the grafts. Taken
      together, the present physiological and histochemical data indicate that it is
      possible to obtain transplants containing a specific monoaminergic population
      within the brainstem from human fetal fragments and to maintain these transplants
      in oculo in athymic nude rats for at least 15 months, during which time
      noradrenergic neurons develop.

PMID- 1397179
TI  - Transynaptic regulation of low-affinity p75 nerve growth factor receptor mRNA
      precedes and accompanies lesion-induced collateral neuronal sprouting.
AB  - The bilateral sympathetic innervation of the rat pineal gland from the two
      superior cervical ganglia (SCG) is a useful model system to investigate the
      mechanisms by which intact neurons compensate for neuronal losses. Cutting of the
      internal carotid nerve (ICN) on one side has been shown to result in the removal
      of approximately one-half of the innervation to the pineal gland within 2 days.
      This denervation is followed by the development of collateral neuronal sprouting
      from the contralateral "intact" SCG, most of which takes place during the next 2
      days. Using a solution hybridization protection assay, levels of low-affinity NGF
      receptor p75NGFR mRNA (pg/microgram total RNA) were found to be increased 25%,
      with no change in cyclophilin mRNA, in the SCG contralateral to the lesion
      performed 1 or 3 days earlier. In situ hybridization with a 35S riboprobe
      complementary to p75NGFR mRNA demonstrated a large increase in this mRNA in some
      cells of this intact SCG at both 1 and 3 days after a contralateral ICN cut
      lesion. The clustering of these cells toward the rostral portion of the SCG
      suggests that they may overlap with the population of sympathetic neurons which
      provides innervation to bilaterally innervated structures such as the pineal
      gland. The nature of the signals involved in the regulation of NGF receptor mRNA
      levels and their role in initiating and maintaining collateral sprouting remain
      to be fully established. Nevertheless, the time course of the changes in mRNA
      levels suggests that regulation of the low-affinity NGF receptor gene may be
      involved in the sequence of events associated with the collateral sprouting
      response by intact sympathetic nerve cells following partial denervation.

PMID- 1397180
TI  - Sensory nerves impair sympathetic reinnervation and recovery of smooth muscle
      function.
AB  - Neuronal populations projecting to a common target may compete for neurotrophic
      substances. To determine if competition impairs target reinnervation, we examined
      the effect of capsaicin-induced sensory denervation on sympathetic nerve ingrowth
      to the sympathectomized rat superior tarsal smooth muscle. In tarsal muscles with
      intact sympathetic innervation, capsaicin injection on Day 2 reduced numbers of
      perimuscular CGRP-ir sensory nerves by 68% at 3-4 months; however, it did not
      alter dopamine-beta-hydroxylase-ir nerve density, response to nerve stimulation,
      or tarsal muscle adrenoceptor-mediated contraction. Tarsal muscles denervated by
      ipsilateral superior cervical ganglionectomy on Postnatal Day 4 were partially
      reinnervated by fibers from the contralateral ganglion, as noted in previous
      studies. Sensory denervation by capsaicin improved sympathetic reinnervation, as
      evidenced by a 174% increase in numbers of DBH-ir nerves and a 62% increase in
      neurally mediated smooth muscle contraction evoked by electrical stimulation of
      the contralateral pathway relative to reinnervated muscles of vehicle-injected
      rats; smooth muscle function was also influenced, as indicated by a decrease
      toward normal in adrenoceptor sensitivity. Tarsal muscles denervated at 30 days
      were not reinnervated in either vehicle-injected or capsaicin-treated rats,
      indicating that sensory denervation does not extend the developmental window
      during which contralateral reinnervation can occur. Both the vehicle-injected and
      capsaicin-treated preparations with sustained juvenile sympathectomy showed
      sensory hyperinnervation as adults; thus, a chronic reduction in competition from
      sympathetics is a sufficiently powerful stimulus to overcome the decreased nerve
      density induced by neonatal capsaicin treatment. We conclude that sensory nerves
      limit the extent of sympathetic reinnervation and functional recovery that can
      occur following neonatal sympathetic denervation.

PMID- 1397181
TI  - Abnormal cerebellar output in rats with an inherited movement disorder.
AB  - Biochemical and metabolic mapping techniques have consistently identified the
      deep cerebellar nuclei (DCN) of the genetically dystonic rat as a site of
      abnormality. Extracellular single-unit recording techniques were used to assess
      the functional significance of these findings in affected rats and normal
      littermates between 16 and 25 days of age. Cells in the medial nucleus of the
      mutant rats had significantly increased spontaneous firing rates in comparison
      with cells from normal rats. In both the medial and the interpositus nuclei,
      cells from the mutants fired more rhythmically than those from the normal rats.
      When harmaline was administered systemically to activate the olivo-cerebellar
      system, in normal rats, increased firing rate and bursting patterns of activity
      were seen. There was no reliable change in the average firing rate or rhythmicity
      of cells in the medial nucleus of the dystonic rats, although previous studies
      have shown that harmaline activates neurons in the inferior olive in the mutants.
      It is likely that naturally stimulated olivary activity also fails to modulate
      cerebellar output in this model of inherited movement disorder. Anatomical
      studies did not reveal any consistent changes in the number of Purkinje cells,
      the volume of the DCN, or the soma size of DCN neurons. Since the
      electrophysiological findings cannot be ascribed to a loss of the Purkinje cells
      that normally provide an inhibitory input to the cerebellar nuclei, the results
      of this study indicate the presence of a functional defect in the control of
      cerebellar output in the dystonic rat that accounts for the failure of these
      animals to display harmaline tremor and which may be critical to the motor
      syndrome.

PMID- 1397182
TI  - Mechanisms of circulatory homeostasis and response in Aplysia.
AB  - This review concerns the organization and function of arterial vasculature in
      Aplysia californica, especially the vasomotor reflexes that support circulatory
      homeostasis, and fixed patterns of response that may reroute blood flow during
      changes in behavioral state. The observations presented here raise three
      hypotheses for further study: 1) Arterial vasculature is functionally organized
      with precisely structured, independently regulated subdivisions; these are most
      evident for arterial systems serving digestive and reproductive processes; 2)
      arterial musculature is inherently responsive to local pressure changes, having
      both static and dynamic reflexes that promote efficient, evenly-distributed flow
      of blood; and 3) complex, long-lasting behaviors like egg laying have, as part of
      their makeup, equally prolonged and stereotypical changes in the pattern of
      circulation. Taken together, these observations support the view that maintenance
      and adjustment of blood flow in gastropod molluscs is an unexpectedly complex and
      highly integrated component of behavior.

PMID- 1397183
TI  - Evidence for the induction and release of pancreatic folylpolyglutamate hydrolase
      by the ingestion of folyl polyglutamates in the rat.
AB  - Pteroyl polyglutamate hydrolase (folyl conjugase), which hydrolyses the dietary
      polyglutamyl folates into simple forms prior to absorption, has been shown to be
      induced in rat pancreas in response to dietary polyglutamyl folates but not by
      ingestion of synthetic unconjugated folates. Folate absorption, as measured by
      the rise in serum folate levels after ingestion, of dietary conjugated folates is
      impaired in pancreatectomised animals whereas absorption of synthetic simple
      folate is not. A severe build-up of folyl conjugase is observed in the lumen of
      control but not in pancreatectomised animals after dietary folate ingestion.
      These results taken together would suggest that dietary folates are hydrolysed to
      monoglutamyl forms suitable for absorption in the lumen; the hydrolysis is
      catalysed by a luminal folyl conjugase of pancreatic origin induced by dietary
      conjugated folates.

PMID- 1397184
TI  - Short cerebral ischemia and subsequent reperfusion and treatment with stobadine.
AB  - Lipid peroxidation and activities of antioxidative enzymes were studied in the
      brain cortex after short (15 min) cerebral ischemia and reperfusion (10 min) in
      rats. Conjugated dienes (CD) and thiobarbituric acid-reactive substances (TBARS)
      were significantly elevated in the group of rats with ischemia followed by
      reperfusion in comparison to the ischemic animals. Superoxide dismutase (SOD)
      activity significantly increased in the group of animals with ischemia and
      reperfusion. No significant changes in the activities of glutathione peroxidase
      (GP) were observed. Stobadine administered before ischemia or before reperfusion
      decreased the level of TBARS. Stobadine probably prevents malondialdehyde (MDA)
      formation from hydroperoxide or might elevate the activity of aldehyde
      dehydrogenase. In contradiction to the findings after long-lasting (4 h) ischemia
      and subsequent reperfusion, no decrease in the concentration of CD or in the
      activity of SOD or GP was found.

PMID- 1397185
TI  - Phase response curve to anisomycin in tau mutant hamsters.
AB  - Administration of the protein synthesis inhibitor, anisomycin, to wild type
      hamsters produces phase shifts in their circadian rhythms that have similarities
      to shifts produced by non-photic behavioral stimulation. A mutation that shortens
      the period of rhythms in hamsters results in altered responsiveness to non-photic
      input. However, responses of the mutants to anisomycin are unaffected: their
      phase response curve (PRC) for anisomycin is similar to that of wild types. This
      suggests that 1) anisomycin is not acting on mechanisms specifically involved in
      non-photic behavioral phase shifting, and 2) the mutation affects the non-photic
      input pathway or the pacemaker itself at a point that is upstream from
      anisomycin's site of action.

PMID- 1397186
TI  - Anti-muscarinic activity of a family of C11N5 compounds isolated from Agelas
      sponges.
AB  - In a search for potential target sites for C11N5 compounds obtained from marine
      sponges of the genus Agelas we evaluated their interaction with muscarinic
      acetylcholine receptors from rat brain membranes. In competition experiments with
      3H-QNB these compounds displayed the following rank order of potency: sceptrin
      greater than oroidin greater than or equal to dibromosceptrin greater than or
      equal to clathrodin. Sceptrin (50 microM) was shown to be a competitive inhibitor
      of 3H-QNB binding as revealed by Scatchard analysis. The results demonstrate the
      ability of these compounds to interact with multiple target molecules in the
      micromolar range.

PMID- 1397187
TI  - Isometachromin, a new cytotoxic sesquiterpenoid from a deep water sponge of the
      family Spongiidae.
AB  - Isometachromin (1), a new sesquiterpene-quinone that is related structurally to
      metachromin C (2), and the known compounds ilimaquinone (3) and 5-epi
      ilimaquinone (4), were isolated from a deep water sponge in the family
      Spongiidae; the structure of isometachromin was elucidated by spectral methods.
      Isometachromin exhibits in vitro cytotoxicity against the human lung cancer cell
      line A549 (IC50 = 2.6 micrograms/ml), but not against P388 murine leukemia (IC 50
      > or equal to 10 micrograms/ml) and also exhibits antimicrobial activity.

PMID- 1397189
TI  - Adhesive grass spikelet with mammalian hair in Dominican amber: first fossil
      evidence of epizoochory.
AB  - Discovery of a female spikelet of the grass genus Pharus (Gramineae:
      Bambusoideae: Phareae) in association with mammalian hair in Dominican Republic
      amber provides the first fossil evidence of epizoochory. Hooked macrohairs on the
      lemma of the spikelet show that morphological modifications in grasses for
      dispersal by attachment to the surface of animals were present in the Late
      Eocene. The fossil also represents 1) the second-oldest undoubted macrofossil
      record of the Gramineae, 2) the earliest record of a fossil grass that can be
      assigned to an extant genus, 3) the earliest undoubted record of a member of the
      bamboo subfamily and 4) the only known fossil of Pharus.

PMID- 1397188
TI  - Differential olfactory perception of enantiomeric compounds by blind subterranean
      mole rats (Spalax ehrenbergi).
AB  - The behavior of mole rats (Spalax ehrenbergi) near pairs of enantiomeric
      compounds was examined in 901 two-choice experimental tests. Positioning of the
      nest and food store and the preferred location of the tested animal were used to
      assess attraction or aversion to the tested odorants. The results indicated that
      mole rats respond differentially to odors of stereoisomers (enantiomers of
      carvone, citronellol, and fechone). They responded to one enantiomer of each
      tested pair but were indifferent to or did not smell the other. Both sexes were
      attracted to the odor of R-(-)-carvone and repelled by the odor of (+)
      citronellol. Females were attracted to the odor of (-)-fenchone while males had
      no preference. By contrast, all animals were indifferent to or did not smell the
      odor of S-(+)-carvone, (-)-citronellol, and (+)-fenchone. Further research to
      distinguish between these alternatives (indifference vs hyposmia/anosmia) is
      suggested.

PMID- 1397190
TI  - Ancylostoma ceylanicum infection in female hamsters: an observation on altered
      reproductive function.
AB  - Reproductive performances of female hamsters were investigated during Ancylostoma
      ceylanicum (hookworm) infection. Animals having the highest levels of infection
      (34.96 +/- 1.11 worms) showed degenerative changes in the reproductive system.
      Ovaries of infected animals contained a few primary or secondary follicles. On
      cocaging with males of proven fertility, only 7-8% (80% in controls) of the
      infected females mated but did not conceive as evidenced by the absence of
      corpora lutea or implantation sites on day 10 postcoitum. Animals with low worm
      burdens (5.94 +/- 0.65 worms), however, showed almost normal fertility. The
      uterine weight bioassay and compensatory ovarian hypertrophy suggest strong
      suppression of pituitary gonadotrophin contents in infected females. Resorptive
      effects on the pregnancy outcome of infected female hamsters were also recorded.

PMID- 1397191
TI  - Lipid-laden white blood cells in the circulation of patients with coronary heart
      disease.
AB  - The total lipid content of white blood cells from healthy donors and patients
      with angiographically documented atherosclerosis of coronary arteries (CHD
      patients) was determined by flow cytofluorometry. The cells of donors were
      homogeneous with respect to intracellular lipid level. However, two
      subpopulations of white blood cells were identified in CHD patients based on
      their lipid content. The first population was identical to cells of donors with
      regard to lipid content, whereas cells of the second subpopulation (10 to 60% of
      the total cell number) had a four- to eightfold greater amount of intracellular
      lipid. The main classes of lipids accumulated in these cells were triglycerides
      and cholesteryl esters. It is postulated that the occurrence of lipid-laden cells
      in the blood may be used as an indicator of the presence of atherosclerotic
      lesions in human coronary arteries.

PMID- 1397192
TI  - Tight junction permeability and liver plasma membrane fluidity in lithocholate
      induced cholestasis.
AB  - The present study correlated the reversibility of bile flow (BF) impairment with
      biochemical and morphological changes in the liver after injection of a
      cholestatic dose (12 mumole/100 g body weight) of lithocholic acid (LCA). BF
      declined maximally at 60 min but recovered totally at 210 min after LCA
      treatment. During the cholestatic period, there was an increase in tight junction
      permeability as measured by the bile to plasma (B/P) ratio of inulin and using
      lanthanum as a tracer. Cholesterol content and the cholesterol/phospholipid ratio
      in liver plasma membranes (LPM) were augmented while the fluidity of bile
      canalicular membranes (BCM) was decreased at 30 and 60 min after LCA injection.
      These changes in cholesterol content and membrane fluidity seemed to be
      correlated with LCA incorporation in LPM; their reversal at 120 min preceded the
      recovery of BF (210 min). Some biochemical disorders were evident after LCA
      injection, but they did not correlate with the variation in BF. These data
      suggest that increased tight junction permeability and decreased BCM fluidity are
      important pathogenic steps in LCA-induced cholestasis.

PMID- 1397193
TI  - Antiatherosclerotic effects of antioxidants are lesion-specific when evaluated in
      hypercholesterolemic New Zealand white rabbits.
AB  - Oxidative modification of LDL may represent an initiating event in the formation
      of monocyte-macrophage foam cells, a major cell present in fatty streaks and
      atherosclerotic fibrous plaques. Therefore, we studied the effect of such
      antioxidants as probucol (500 mg/kg) and vitamins E and C (500 mg/kg each) on the
      regression of induced iliac-femoral lesions and progression of naturally
      occurring thoracic aortic fatty streak lesions in hypercholesterolemic New
      Zealand White rabbits. Following an initial 9-week lesion induction phase, both
      therapies were evaluated for 8 weeks. Probucol lowered plasma cholesterol 47%
      while vitamins E and C had no effect on plasma cholesterol. Probucol decreased
      the cholesteryl ester (CE) content of the thoracic aorta by 31% without changing
      the thoracic aortic lesion coverage. Vitamins E and C decreased thoracic aortic
      CE content by 40% and lesion coverage by 46%. Neither probucol nor vitamins E and
      C altered the CE content, lesion size, or macrophage/lesion ratio of the iliac
      femoral artery. Thus, we conclude that the effects of antioxidants are specific
      to the stage of atherosclerotic lesion development. Antioxidant therapy alters
      the progression and cholesteryl ester enrichment of diet-induced thoracic aortic
      fatty streaks but has no effect on the progression and/or regression of more
      complicated injury-induced iliac-femoral lesions.

PMID- 1397194
TI  - Detection of migration stimulating activity in wound fluid.
AB  - Fetal skin fibroblasts produce a soluble "migration stimulating factor" (MSF)
      which is not made by their normal adult counterparts. MSF stimulates the
      migration of adult skin fibroblasts into 3D collagen gels, thus providing the
      basis of a convenient bioassay for its presence. We have previously reported that
      MSF stimulates hyaluronic acid (HA) synthesis by adult skin fibroblasts and that
      this effect on matrix deposition appears to be responsible for the observed
      increase in cell motility. In the present study, wound fluid samples were
      collected from 18 patients undergoing surgery for various nonmalignant conditions
      and these were then fractionated according to the protocol used to isolate MSF
      from fetal fibroblast-conditioned medium. Detectable levels of migration
      stimulating activity were present in 17/18 (94%) of these samples. Paired serum
      samples obtained both pre- and postoperatively from five patients with positive
      wound fluid samples were also analyzed for MSF activity; such activity was found
      in only 1/5 (20%) of the preoperative and 0/5 (0%) of the postoperative serum
      samples. These data suggest that the MSF present in wound fluid is not derived
      from a plasma transudate or from platelet degranulation, but may reflect the
      transient and localized reinitiation of MSF production by adult fibroblasts in
      response to wounding. Taken together with previous observations regarding the
      effect of MSF on fibroblast migration and HA synthesis, our data suggest a
      possible physiological function of MSF in the wound healing response. Previous
      studies have revealed that MSF is produced by a subpopulation of apparently
      persistent fetal-like skin fibroblasts obtained from breast cancer patients and
      is also found in the serum of these individuals. Wound fluid and serum samples
      were accordingly collected from patients undergoing surgery for various types of
      malignant conditions or with a previous history of cancer; detectable levels of
      MSF activity were found in 8/10 (80%) of these wound fluid samples, 2/3 (66.6%)
      of the preoperative, and 3/3 (100%) of the postoperative paired serum samples.
      These findings suggest that the presence of detectable serum levels of MSF is not
      restricted to breast cancer and may be a general feature of malignant disease.

PMID- 1397195
TI  - The ecology of Cryptococcus neoformans.
AB  - Environmental isolations have established that Cryptococcus neoformans var.
      gattii serotype B appears to have a specific ecological association with
      Eucalyptus camaldulensis. The global distribution of the tree appears to
      correspond to the epidemiologic distribution of cryptococcosis caused by C.
      neoformans var. gattii. The epidemiology of cryptococcosis can primarily be
      explained by exposure to an infective aerosolized inoculum, such as basidiospores
      released from specific host plants and/or desiccated blastoconidia (yeast cells)
      disseminated from accumulations of dried pigeon dung. The ecology of C.
      neoformans still remains largely unresolved, studies on the host-parasite
      interaction between serotype B and E. camaldulensis are still in progress, and
      extensive environmental searches are now underway to determine the natural
      habitats of serotypes A, C and D.

PMID- 1397196
TI  - Incidence of dermatophytoses in rabbit farms in Catalonia, Spain, and its
      repercussion on human health.
AB  - Over the past decades there has been an important increase in the incidence of
      dermatophytoses in humans as a result of contact with animals, although
      etiological agents can vary as can the animals transmitting the disease. A large
      scale study was carried out in 220 farms raising rabbits for consumption. Most of
      the farms (85%) were located in the autonomous community of Catalonia (Spain).
      Mycological studies showed that 79.5% of the rabbits were infected with
      Trichophyton mentagrophytes var. granulosum. Microsporum canis was isolated in
      only two animals, which had been imported from France. Healthy animal carriers
      were detected in 3.2% of the apparently non-infected farms. T. mentagrophytes
      were also found in samples taken from rabbits' nests and from the surrounding
      environment of the two infected farms. In a survey carried out among the staff
      responsible for the care of the animals, 77% of those working on infected farms
      suffered or had suffered dermatophytic lesions. This was confirmed in 8 out of 10
      cases sampled. Attention is drawn to the high incidence of dermatophytoses in
      rabbits on farms and the importance of T. mentagrophytes as the etiological agent
      of tinea in people in close contact with infected animals.

PMID- 1397198
TI  - Genetic susceptibility to dermatophytosis.
AB  - Clustering of cases of dermatophytosis suggests that inherited susceptibility may
      play a part in determining the epidemiology of some forms of this infection,
      notably tinea imbricata. Some studies of T. concentricum infection show that
      autosomal recessive susceptibility may provide an answer although this is not the
      case in all endemic areas. Further support comes from the association between
      dermatophytosis in man and inherited conditions such as atopy, chronic
      mucocutaneous candidosis and tylosis as well as experimental data showing that
      susceptibility to dermatophytosis in mice varies in different inbred strains.
      Possible mechanisms are discussed.

PMID- 1397197
TI  - Morphological and biochemical variability of Microsporum canis strains.
AB  - Seventy-two strains of Microsporum canis, of different origins, were examined
      from a morphological point of view and tested in relation to their hydrolytic
      activity on tyrosine, xanthine, casein, gelatin, their ureasic activity and their
      capacity to assimilate different nitrogenous substances. The morphological
      aspects, that vary within the M. canis isolates, were constant in the strains
      isolated from rabbits. A strain with particular features was isolated many times
      from the dogs and cats coming from the same breeder. In one case of
      pseudomycetoma, different isolates suggested the co-existence in animals of two
      different strains, one present on fur, the other responsible for deep lesions.

PMID- 1397199
TI  - Inhibition of adherence of Candida albicans to acrylic by a chitin derivative.
AB  - The purpose of this study was to assess the effect of a chitin derivative (CSE)
      on the adherence of Candida albicans to acrylic. Fungal adherence to acrylic
      dentures is considered an essential step in the development of denture
      stomatitis. Adherence of C. albicans to acrylic pieces (5 x 5mm) was assessed
      microscopically using a calibrated ocular objective and expressed as number of
      adherent yeasts/mm2 of acrylic. CSE was prepared from commercial chitin (crab
      shell) and from chitin isolated from C. albicans blastospores. The effect of both
      CSE types on the adherence of C. albicans to acrylic was examined in two
      experimental systems: CSE present during the adherence assay and acrylic pieces
      pretreated with CSE prior to the assay. Both CSE types exerted a significant
      inhibitory effect when tested in the two experimental systems. These findings are
      significant for possible prevention of denture stomatitis.

PMID- 1397200
TI  - Immunohistologic diagnosis of systemic mycoses: an update.
AB  - Fluorescent antibody, immunoperoxidase and gold-silver staining methods for the
      rapid and accurate diagnosis of systemic mycotic infections are currently
      performed in a few specialized laboratories. These methods have proved applicable
      to formalin-fixed, paraffin-embedded tissues, and are reliable for identifying
      therein antigens of infectious dimorphic, monomorphic filamentous, and yeast-like
      fungal pathogens, i.e., Aspergillus spp., Blastomyces dermatitidis, Candida spp.,
      Coccidioides immitis, Cryptococcus neoformans, Fusarium spp., Histoplasma
      capsulatum, Paracoccidioides brasiliensis, Pseudallescheria boydii, and
      Sporothrix schenckii. Most of the available reagents are derived from multiple
      adsorbed polyclonal antisera. However, problems occur in the production of
      uniform and standardized species- or genus- specific antibodies. Monoclonal
      antibodies, although promising, have to date not eliminated these problems.
      Immunohistologic methods will become more routinely used in clinical laboratories
      as these problems are resolved and more sensitive and specific reagents become
      commercially available.

PMID- 1397201
TI  - Phaeohyphomycosis caused by Bipolaris spicifera: an informative case.
AB  - A case of phaeohyphomycosis caused by Bipolaris spicifera involving the brain and
      sinuses is presented. The patient survived following surgery and ketoconazole
      therapy, which successfully treated both the sinus and the brain infections.

PMID- 1397202
TI  - Cerebral phaeohyphomycosis caused by Xylohypha bantiana, with a review of the
      literature.
AB  - A 76-year-old male with chief complaints of back and right leg sciatica was
      hospitalized. His abdominal CT scan revealed lumber spondylitic stenosis. A
      laminectomy was performed. Postoperatively, he became febrile, aphasic and had
      grand mal seizure. A left craniotomy of the front abscess, seen in the CT scan,
      was performed. H and E stained smears of drainage revealed dematiaceous, septate
      hyphae. Cultures of the abscess drainage grew an olivaceous-grey fungus. Based on
      macro- and micro-morphological characters, growth at 42 degrees C, and
      exoantigenic analysis, the patient's fungus was identified as Xylohypha bantiana.
      Treatment with amphotericin B and 5-fluorocytosine was initiated. Despite
      surgical procedures and antifungal therapy, the patient's condition deteriorated
      and he died a few weeks later due to cerebral edema. The case reported here is
      the first microscopically, culturally, histopathologically and exoantigenically
      proven case of phaeohyphomycosis caused by X. bantiana in the province of Alberta
      and from Canada. A review of the literature on cases of X. bantiana infections
      has also been presented.

PMID- 1397203
TI  - Entomophthoromycosis due to Conidiobolus.
AB  - Entomophthoromycosis due to Conidiobolus coronatus is a granulomatous infection
      characterized by lesions that originate in the inferior turbinate, spread through
      ostia and foramina to involve the facial and subcutaneous tissues and paranasal
      sinuses. The majority of the cases have been described from areas of tropical
      rainforest in West Africa, agricultural and outdoor workers (aged 20-60 years)
      being the ones most frequently affected. The fungus is common in soil and
      decaying vegetation. Infection probably occurs by implantation of the spores of
      the fungus in nasal mucosa. C. incongruus is a rare agent of the disease, so far
      known only from two cases with lesions involving the pericardium, mediastinum,
      lungs, liver, oesophagus and jejunum. C. coronatus is known to cause a clinically
      similar disease in horses, mules, a dolphin and a chimpanzee. A characteristic
      histological feature is the presence of thin-walled, broad, often septate hyphae
      or hyphal fragments with a thick eosinophilic sheath, frequently phagocytosed
      within giant cells. The fungus is known to produce in vitro several enzymes,
      e.g., elastase, esterase, collagenase and lipase, which have a possible role in
      pathogenicity. A concentrated brain heart infusion culture filtrate antigen is
      useful for immunodiagnosis. Several drugs e.g., potassium iodide, cotrimoxazole,
      amphotericin B, ketoconazole and itraconazole have been tried with varying
      success. Investigations on the immunology of disease and the role of proteases
      and lipases in the pathogenesis of infection is an important area of further
      research.

PMID- 1397204
TI  - Protothecosis: a report of two cases in Japan and a review of the literature.
AB  - Protothecosis is an emerging opportunistic infection caused by species belonging
      to the genus Prototheca. Two Japanese cases of protothecosis are documented with
      a critical review of the literature. A current perspective concerning the
      microbiology and disease entity of protothecosis is described in detail.

PMID- 1397206
TI  - In vitro sensitivity of Penicillium marneffei and Pythium insidiosum to various
      antifungal agents.
AB  - Ten isolates of Penicillium marneffei and eight of Pythium insidiosum were tested
      for their in vitro sensitivity to amphotericin B, hamycin (a polyene heptaene),
      two water-soluble analogs of amphotericin B and hamycin, namely, JAI-Amb, and JAI
      hamycin,5-fluorocytosine, fluconazole, itraconazole,ketoconazole and miconazole.
      Itraconazole manifested the strongest activity against all of the 10 isolates of
      P. marneffei and would be the drug of choice in the treatment of penicilliosis
      due to P. marneffei. The polyene antibiotics amphotericin B and hamycin and their
      water-soluble analogs showed no appreciable activity against P. insidiosum.
      Pytium insidiosum isolates were sensitive to fluconazole, ketoconazole, and
      miconazole. Miconazole exhibited the strongest in vitro activity against all of
      the 8 isolates of P. insidiosum, followed by ketoconazole.

PMID- 1397207
TI  - Surveillance and treatment of liver transplant recipients for candidiasis and
      aspergillosis.
AB  - Between June 1988 and May 1991 88 orthotopic liver transplants and 1 liver and
      pancreas transplant were performed at the Liver Transplantation Department of the
      Ospedale Maggiore of Milan. All the patients underwent mycological surveillance
      and received antifungal prophylaxis with oral amphotericin B (6000 mg/day) or
      oral or intravenous fluconazole (200 mg/day) from the time of their transplant.
      The incidence of Candida colonization was 67%. Fluconazole was superior to oral
      amphotericin B in the treatment of C. albicans colonization (9/9 vs 6/15), but
      less effective in the treatment of colonization by other Candida spp. (0/3 vs
      3/3). Deep-seated candidiasis developed in 5 patients, caused by C. albicans in 4
      cases and C. krusei in 1. C. albicans infection resolved rapidly with fluconazole
      in 2 subjects, with intravenous amphotericin B alone in 1, and with amphotericin
      B plus flucytosine in the other. On the contrary, C. krusei infection did not
      respond to treatment with amphotericin B combined with flucytosine. Aspergillosis
      was diagnosed in 11 patients, of whom 4 died from invasive aspergillosis, despite
      15 and 26 days of amphotericin B treatment in 2. In another patient invasive
      aspergillosis, diagnosed a few hours before retransplantation, improved with
      liposomal amphotericin B, but this man died from cytomegalovirus infection one
      month later. Aspergillosis was eradicated by itraconazole in 4 other patients and
      by topical amphotericin B in 2 whose infection was localized to surgical wound.

PMID- 1397205
TI  - Drug resistance in human pathogenic fungi.
AB  - Since the therapy of the mycoses, particularly the systemic mycoses, is
      relatively long-term in nature, emergence of resistance to antifungal drugs
      during the treatment of period would be of considerable clinical importance.
      However, most reports of resistance to antifungal agents among human pathogenic
      fungi indicate that naturally-occurring resistance is very rare, and that the
      induction of resistant mutants or variants is much more difficult to achieve in
      vitro and in vivo than with bacteria. As a matter of fact, amphotericin B and
      some other classic antifungals have not as yet posed a broadly significant
      problem relative to drug resistance despite their widespread and frequent use.
      Fungal resistance has thus received little attention, in contrast to the critical
      importance of bacterial resistance frequently caused by a variety of
      antibacterial chemotherapeutic agents, until a single exception to this
      generalization arose with the advent of flucytosine. This new development has
      aroused great interest in the problem of fungal resistance among the scientists
      involved with medical mycology. It is generally believed that fungi, like
      bacteria, are intrinsically capable of developing resistance to antifungal
      agents. As illustrated by flucytosine, inherently resistant mutants to
      antifungals occur within sensitive strains of human pathogenic fungi with
      significant frequency. Given the relatively high degree of such primary
      resistance, these mutants should develop secondary resistance during therapy,
      thus resulting in considerable limitations in the clinical usefulness of the
      antifungals. Virtually, all unsuccessful cases of mycoses treated with some of
      the recently exploited antifungal drugs, albeit scarce to date, would obviously
      be attributable to the occurrence of secondary resistance. The exploitation of
      new antifungal drugs thus requires investigations of their resistance as one of
      the most important research projects to be undertaken before receiving approval
      for use on humans. This paper reviews from various aspects the literature on
      resistance to various classic and novel antifungal agents among human pathogenic
      fungi. The resistance of some nonpathogenic fungi to these agents will also be
      described from genetic and biochemical points of view.

PMID- 1397208
TI  - Distribution and antimicrobial susceptibility of Rhodococcus equi from clinical
      specimens.
AB  - Rhodococcus equi, an unusual gram positive aerobic actinomycete, was first
      described as a respiratory pathogen of livestock in 1923. Reports of human
      clinical illness have emphasized R. equi as a cause of invasive pulmonary
      infection in severely immunocompromised patients and, recently, have implicated
      it as a cause of pneumonia, bacteremia and disseminated infection in HIV-infected
      patients. To determine the distribution of R. equi we evaluated 107 isolates
      referred to the Centers for Disease Control (CDC) during the period January 1973
      through December 1990. The sites of these 107 isolates (101 patient and 6 animal
      isolates) were: blood (32 isolates), sputum (30), lung tissue (13) and other site
      (32). Before 1983, when the first R. equi isolate from an HIV-infected patient
      was received, CDC received a total of 52 patient isolates. In addition, during
      this 10 year period, R. equi isolates were received from more than one site from
      only one patient. However, during the two year period 1989-1990, we identified 8
      patients with underlying HIV infection and R. equi pneumonia who accounted for 29
      of 35 (83%) R. equi patient isolates; 6 of these patients also had bacteremia and
      three died with disseminated R. equi infection. No isolates were resistant to
      amoxicillin-clavulanate, ampicillin-sulbactam, gentamicin or imipenem, and few
      (less than 5%) isolates were resistant to erythromycin, rifampin, tetracycline,
      and trimethoprim-sulfamethoxazole. These results suggest that HIV-infected
      patients, in particular, are predisposed to develop invasive pulmonary, fatal
      disseminated R. equi infection (or both), and appropriate antimicrobial
      susceptibility testing of clinical isolates may improve the effectiveness of
      therapy of R. equi-infected patients.

PMID- 1397209
TI  - DNA relatedness, karyotyping and gene probing of Candida tropicalis, Candida
      albicans and its synonyms Candida stellatoidea and Candida claussenii.
AB  - Isolates of Candida albicans with varied phenotypes, including sucrose-negative
      variants (C. stellatoidea, serotypes A and B) and avirulent germ tube-negative
      forms (C. claussenii) showed significant (greater than 90%) DNA relatedness to
      classical C. albicans, but insignificant relatedness to C. tropicalis and sucrose
      negative C. tropicalis. A transverse alternating-field gel electrophoresis
      procedure (TAFE) showed discrete karyotype patterns among the phenotypic variants
      of C. albicans including the sucrose-negative C. stellatoidea. The number of
      chromosome-sized DNA bands for C. tropicalis (7 bands) were within the range of
      bands observed for C. albicans (5 to 10 bands). The general DNA-migration pattern
      for C. albicans appeared distinct from that of C. tropicalis. An aspartyl
      proteinase (PrA) gene probe from C. albicans hybridized with chromosomal DNA from
      C. albicans, C. claussenii and C. stellatoidea but not with that from C.
      tropicalis.

PMID- 1397211
TI  - Anaerobic yeast killer systems.
AB  - The influence of anaerobic conditions on the expression of the killer phenomenon
      of several yeast isolates belonging to recognized killer systems coded by
      different genetic determinants (Pichia spp., Kluyveromyces lactis, Saccharomyces
      cerevisiae) was studied. Anaerobiosis influenced the activity of killer toxins
      from some individual isolates of the genera Pichia and Saccharomyces on sensitive
      strains of P. anomala, K. lactis and Candida albicans. However, no influence was
      detectable on a S. cerevisiae sensitive isolate. Thus, anaerobic conditions seem
      to interfere more with the metabolic process of sensitive strains than with toxin
      production by killer yeasts. The selection of a panel of killer yeasts, able to
      display their activity against reference sensitive yeast isolates under anaerobic
      conditions in a medium that favored the growth of anaerobes, allowed the use of
      the killer system to type Bacteroides fragilis isolates for epidemiological
      purposes.

PMID- 1397210
TI  - Is Pneumocystis carinii a deep mycosis-like agent?
AB  - Pneumocystis carinii is a widespread eukaryotic microorganism found in the lungs
      of healthy mammals, including humans. It is able to proliferate extensively in
      the alveoli, becoming an important agent of severe pneumonitis in
      immunosuppressed hosts, especially in persons suffering from AIDS. The taxonomic
      position of P. carinii is uncertain. Typical cytoplasmic organelles of eukaryotic
      cells have been found and described in the parasite. Biochemical research is
      hindered by the lack of an efficient in vitro culture system. Results of
      comparative study of nucleic acid sequences suggest that Pneumocystis is a
      fungus. However, ultrastructural, biochemical and nucleic acid homology insights
      appear as clearly insufficient to class Pneumocystis. Pneumocystis infection
      might be acquired, as deep mycoses, from environmental sources through the
      respiratory tract. Thus, the hypothesis of an environmental stage of the parasite
      must be considered. Pneumocystis might be seen as a widespread pathogenic
      dimorphous fungus. As fungal agents, P. carinii is able to disseminate from the
      infected lung to other organs. However, deep mycoses and pneumocystosis induce
      different histopathological changes in the host. Furthermore, deep fungal
      infections, unlike pneumocystosis, cannot be transmitted from one infested host
      to another one. Beside these two aspects, pneumocystosis shares many features
      with deep mycoses. Research on the epidemiology of pneumocystosis is needed.

PMID- 1397212
TI  - Experimental gastrointestinal and disseminated candidiasis in immunocompromised
      animals.

PMID- 1397213
TI  - Five years of sentinel surveillance of acute respiratory infections (1985-1990):
      the benefits of an influenza early warning system.
AB  - For the last five years, the Brussels Institute of Hygiene and Epidemiology has
      been involved in the surveillance of acute respiratory infections (ARI). The four
      indicators used (number of encounters of ARI by GP's/100 encounters, virus
      isolations, absenteeism and mortality) are discussed. A regression procedure is
      applied to the data collected by a sentinel network of general practitioners
      (GP's). This procedure permits the baseline to be visualized and an epidemic
      threshold to be determined in order to recognize early an influenza outbreak. The
      traditional use of flu-like illnesses as an indicator might be improved by the
      addition of non-specific ARI which are more precocious, especially in children.
      The criteria for an accurate definition of an influenza epidemic are discussed.
      The same mathematical model can be used for the analysis of mortality linked with
      an outbreak. It shows that the last epidemic in the winter 1989-1990 was
      responsible for about 4900 deaths directly or indirectly related to influenza.

PMID- 1397214
TI  - Immunization of elderly volunteers with the 1988-89 inactivated whole influenza
      vaccine: assessment of antibody responses by haemagglutination inhibition and
      single radial haemolysis tests.
AB  - The immunogenicity of inactivated whole trivalent influenza vaccines
      (A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2), and B ijing/1/87) recommended for
      the 1988-89 winter season was evaluated in 236 elderly (mean age 71 years) high
      risk volunteers. An overall significant increase in the number of subjects with
      protective haemagglutination inhibiting (HI) antibodies (titer > 1:40) against
      vaccine components was observed after vaccination. Nevertheless, a percentage of
      individuals (ranging from 56% to 62%) remained without protective antibodies and
      the number of people showing a positive response was limited (from 32% to 41%).
      By the comparative analysis of the results obtained examining the presence of
      protective levels of antibody in the sera from 91 volunteers using HI versus the
      single radial haemolysis (SRH) test, we obtained evidence for a higher
      sensitivity of SRH technique especially against B antigen.

PMID- 1397215
TI  - The role of breast self-examination in early breast cancer detection (results of
      the 5-years USSR/WHO randomized study in Leningrad).
AB  - A randomized population-based study has been carried out since 1985 in Leningrad
      in order to evaluate the efficacy of breast self-examination (BSE) in early
      breast cancer detection. The population under study covers 120,310 women aged 40
      64 years with no history of breast cancer. About half of these women were exposed
      to BSE training (60,221) and 60,098 women constituted the control group. BSE
      teaching was carried out on a person-to-person basis and each patient received
      the BSE calendar. BSE education sessions resulted in a higher frequency of visits
      to specialists with complaints about "pathology" of the breast, a higher rate of
      referral to a specialized institution for an examination, and a higher number of
      excision biopsies due to a benign lesion (RR = 1.5; 95% C.I. = 1.1 - 1.9) as
      compared with the control group. As a result of examination, 190 breast cancer
      patients in the BSE group and 192 patients in the control group were detected.
      Comparisons of patients from both groups with regard to the size of primary tumor
      and the incidence of metastatic lesion in the regional lymph nodes showed no
      differences. The study is ongoing and all cases of breast cancer in the BSE group
      will be registered up to 1994 and followed-up to 1999; information will then be
      available on the impact of BSE upon breast cancer mortality.

PMID- 1397216
TI  - Maternal diabetes: the risk for specific birth defects.
AB  - We studied the risk for specific birth defects among infants of mothers with
      gestational and chronic diabetes using data collected by the Spanish
      Collaborative Study of Congenital Malformations (ECEMC). For the years 1976 to
      1985, we identified 10,087 infants with malformations and 9,994 control infants;
      155 of the case infants and 89 of the controls were born to diabetic mothers. The
      crude odds ratio for any minor or major defect and insulin-treated diabetes was
      5.5 (95% CI = 1.2, 24.8), and for major malformations it was 8.7 (95% CI = 1.8,
      34.7). The risk for defects involving the central nervous system (CNS), skeletal
      system and cardiovascular system were significantly increased. Infants of non
      insulin-treated diabetic mothers were 2.9 times more likely to have a major
      congenital birth defect (95% CI = 1.2, 7.2). The crude odds ratio for any major
      or minor defect and mothers with gestational diabetes requiring insulin was 1.9
      (95% CI = 1.1, 3.4). Similar risk was observed for major defects (OR = 1.9, 95%
      CI = 1.0, 3.7). These results suggest that infants of insulin-treated diabetic
      mothers have an increased risk of developing malformations of the CNS,
      cardiovascular system and skeletal system. We also found an increased risk for
      specific defect categories among infants of mothers with gestational diabetes
      treated with insulin.

PMID- 1397217
TI  - Risk factors for atrial septal defect.
AB  - The possible effect of environmental factors during pregnancy on the occurrence
      of atrial septal defect (ASD-secundum) in the offspring was studied in 50 cases
      and 756 controls. The cases represented all verified ASDs in Finland during 1982
      1983. The controls were randomly selected from all infants born during the same
      period. Case and control mothers were interviewed by midwives using a structured
      questionnaire approximately three months after delivery. Congenital heart disease
      was more prevalent among parents of cases than those of controls. Maternal
      alcohol consumption during the first trimester of pregnancy appeared to double
      the risk of atrial septal defect (OR = 1.9, CI98 = 1.1 - 3.4). Maternal exposure
      to chemicals at work during the first trimester was more prevalent among the ASD
      group (40.0%) than the control group (26.2%). The risk of ASD was not associated
      with maternal smoking, or coffee, tea or acetosalicylic acid consumption.
      Maternal exposure to video display terminals, microwave ovens, organic solvents,
      anesthetic gases, pesticides or wood preservatives during the first trimester of
      pregnancy were not associated with the risk of an atrial septal defect. It is
      concluded that some common physical and chemical exposures during early pregnancy
      should not necessarily be considered risk factors for atrial septal defect.

PMID- 1397218
TI  - Incidence of congenital toxoplasmosis in live Guatemalan newborns.
AB  - Five hundred and fifty samples of blood collected from the umbilical cords of an
      equivalent number of newborns were analyzed for serological evidence of
      congenital toxoplasmosis based on the detection of IgG and IgM. Six newborns
      presented serological evidence of congenital toxoplasmosis (IgM > 1:5, < 80
      IU/ml), which represents an incidence of 10.9 per 1000 live births. During
      pregnancy four of the mothers of these six newborns were asymptomatic, whereas
      the other two mothers presented non-specific signs and symptoms. The six newborns
      did not present positive signs of acute toxoplasmosis at birth. Three false
      positive were identified, all secondary to the presence of a rheumatoid (RF)
      and/or antinuclear factor (ANF). And in one of them the diagnosis of congenital
      syphilis was confirmed. The percentage of women that tested serum positive for
      IgG antibodies increased with age, with 55.8% of the pregnant women testing serum
      negative, therefore carrying the risk of acquired toxoplasmosis in future
      pregnancies.

PMID- 1397219
TI  - The prediction of coronary heart disease in different population samples.
AB  - Two population samples of men aged 46-65 years were examined for the measurement
      of some cardiovascular risk factors and followed up for 6.5 years. The two groups
      were: 1) 3338 men belonging to occupational groups examined in Rome (ROG) in 1979
      81 and 2) 1543 men belonging to two demographic samples of rural areas located in
      northern and central Italy (IRA) examined in 1965. In men free from previous
      myocardial infarction the rate of fatal coronary events was 18.0 in the ROG group
      and 17.5 per 1000 in the IRA group. Five established risk factors (age, systolic
      blood pressure, serum cholesterol, cigarette consumption and body mass index)
      were used in a multivariate model for predicting coronary deaths. The
      coefficients of the multiple logistic function were similar in the two
      populations group. However, when the IRA coefficients were applied to the ROG
      factors, they predicted 43 events instead of 58 (under-estimation of 26%; p <
      0.05), whereas the ROG coefficients predicted 31 events instead of 26 in the IRA
      sample (over-estimation of 19%; p = n.s.). A model which included the pool of the
      two populations and a dummy-variable for the identification of each of them,
      suggested that being a member of the ROG group is accompained, everything else
      being equal, by an extra risk of 26%.

PMID- 1397220
TI  - Characteristics of alcoholics attending "Alcoholics in treatment" clubs in
      northeastern Italy.
AB  - A study on the characteristics of alcoholics attending the "Alcoholics in
      treatment" clubs, a community and family-oriented programme against alcoholism,
      has been conducted in the Friuli-Venezia Giulia region, Northeastern Italy. A
      total of 598 individuals (93% of those contacted) completed the questionnaire,
      431 (72%) were males and 167 (28%) were females. With respect to marital status,
      never married men and widows seemed to be at high risk of alcoholism. Total
      alcohol consumption in males significantly exceeded that in females (X2(1) trend
      18.86 p < 0.001) and this excess mainly seemed to be primarily associated with
      wine (X2(1) trend 32.81 p < 0.001). Younger individuals (< 50 yrs) tended to
      begin drinking earlier and to report higher intake from alcoholic beverages other
      than wine as compared to older individuals (< 50 yrs) (X2(1) trend = 25.25 p <
      0.001). A high percentage of males (30%) reported heavier alcohol intake in their
      father as compared to themselves while only 12 of females reported heavier intake
      in their mother as compared to themselves. Health complaints seemed to be the
      chief reason which prompted individuals, particularly above age 50, to attend
      "Alcoholics in treatment" clubs but awareness of alcohol-related health problems
      played a substantial role, as shown by the very common overestimation of alcohol
      as the primary cause of death in Italy by the individuals attending the club.

PMID- 1397221
TI  - Possible confounders of the relationship between occupational swine contact and
      Yersinia enterocolitica 0:3 and 0:9 antibodies.
AB  - Increased risk of high Yersinia enterocolitica 0:3 and 0:9 antibody content has
      been previously reported in occupations with swine contact. In this study several
      possible confounders of this elevated risk among pig farmers and abattoir workers
      were considered. Only in three instances the standardized risk ratio was
      decreased close to unity, namely after the standardization of Y. enterocolitica
      0:3 IgG antibody positivity for age among abattoir workers, after the
      standardization of Y. enterocolitica 0:9 IgG antibody positivity for farm
      butchering among pig farmers and for smoking among abattoir workers. As the
      decrease did not apply for both pig farmers and abattoir workers and for both 0:3
      and 0:9 serotypes considered, it seems reasonable to assume that the three
      decreases represent products of multiple testing inherent in this kind of search
      of confounders rather than any true effects. In view of the present knowledge on
      the determinants of yersinia antibodies in populations, the crude risk ratios for
      elevated yersinia antibodies can be held to be reasonably unconfounded.

PMID- 1397222
TI  - Typhoid fever in the Neapolitan area: a case-control study.
AB  - Typhoid fever is endemic in the Neapolitan area, where its yearly incidence rate
      largely exceeds the corresponding national figure. During the period from January
      to June, 1990, a matched case-control study was carried out in order to identify
      risk factors of the disease in this area; 51 subjects (mean age 27.2 years) with
      typhoid fever were compared with 102 controls matched with respect to age, sex
      and educational level. Consumption of raw shellfish was reported by 76.5% of the
      cases, as opposed to 19.6% of the controls (P < 0.01). Subjects who had eaten
      this food item had a 13.3-fold risk (C.I. 95% = 5.5 - 32.8) of contracting
      typhoid fever. In contrast, no risk was found to be associated with consumption
      of cooked shellfish, raw vegetables, ice-cream, non-potable water, or
      unpasteurized milk. The risk factor identified in this study shows that hazardous
      dietary habits and inadequate sewage treatment facilities, combined with lack of
      sanitation in the harvesting and marketing of shellfish, play a major role in the
      endemicity of typhoid fever in the Neapolitan area.

PMID- 1397223
TI  - Heterogeneity among heat-labile enterotoxins produced by porcine enterotoxigenic
      Escherichia coli.
AB  - The heat-labile enterotoxins (LT) produced by various porcine strains (LTp) of
      enterotoxigenic Escherichia coli were purified to homogeneity and their molecular
      properties were compared with each other. By double gel diffusion and rabbit skin
      permeability test, LTps from WT-1 (LTp-WT-1) and BO-149 (LTp-BO-149) strains were
      antigenically and biologically identical. By polyacrylamide gel electrophoresis
      with sodium dodecyl sulfate (SDS), the mobilities of A and B subunits of LTp (BO
      149) were identical to those of LTp (WT-1). However, on polyacrylamide gel
      electrophoresis without SDS, LTp (BO-149) and LTp (WT-1) differed in mobility,
      suggesting their molecular differences. Though the pI value of the B subunit of
      LTp (BO-149) was identical to that of LTp (WT-1), the pI value of the A subunit
      of LTp (BO-149) was higher than that of LTp (WT-1). These data suggest that there
      is molecular heterogeneity among LTps produced by the two porcine enterotoxigenic
      Escherichia coli strains.

PMID- 1397224
TI  - Enterotoxigenic and necrotizing Escherichia coli in human diarrhoea in Spain.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains of serotype 0153: K-:H45 CFA/I+
      STa+ were associated with two outbreaks of neonatal diarrhoea that occurred in
      two different hospitals of Madrid, in one of which several children died. Two
      other outbreaks were associated with ETEC strains of serotypes 0159: K-:H21 (LT+)
      and 0159: K-:H4 (LT+ STa+) without CFA/I and CFA/II colonization factors.
      Necrotizing E. coli (NTEC) strains of serotype 06:K13, producing the cytotoxic
      necrotizing factor CNF1 and alpha-haemolysin, were also associated with two
      outbreaks of neonatal diarrhoea that occurred in a hospital in Madrid and in a
      hospital in Talavera de la Reina. The results of the characterization of some
      ETEC and NTEC strains isolated from sporadic cases of diarrhoea are also
      discussed.

PMID- 1397225
TI  - Epidemiology and clinical significance of Blastocystis hominis in different
      population groups in Salamanca (Spain).
AB  - A prospective study was carried out to investigate the epidemiology and clinical
      significance of Blastocystis hominis in the following groups of the population of
      the city of Salamanca (Spain): in children attending 11 day care centres and 7
      primary schools, two fecal samples were obtained from each child, and in 1231
      patients attending the Clinical Hospital. A B. hominis incidence of 5.3-10.3% was
      found in the day care centres and an incidence rate of 13.4-19.4% was found in
      the primary schools. All the cases were observed in asymptomatic children. The
      incidence of B. hominis was greater in children older than 3 years in the day
      care centres and in the 10-14 year-old group in the primary schools. A heavier
      parasitization was observed in the boys than in the girls and in the students of
      schools in areas of low socio-economic level. B. hominis was identified in 40
      patients attending the Clinical Hospital (3.25% of all those studied). The
      maximum peak of incidence was found in subjects with ages between 10 and 14
      years. A follow up study was performed on 18 patients parasitized exclusively by
      B. hominis; 7 of these were considered to have acute gastroenteritis and one
      chronic gastroenteritis associated with the protozoan. No statistically
      significant association was observed between the number of B. hominis cells and
      the presence of diarrhoea. Our results show that despite the high number of
      asymptomatic carriers of B. hominis in the juvenile population, this protozoan
      may be, on other occasions, responsible for gastrointestinal symptoms.

PMID- 1397227
TI  - Monoclonal antibody based capture ELISA/ELIFA for detection of Coxiella burnetii
      in clinical specimens.
AB  - A CAPTURE ELISA/ELIFA system based on monoclonal capture and biotinylated
      monoclonal detection antibody is described. The assay is fast, highly specific
      and detects a minimum dose of 2500 Coxiella (C.) burnetii particles. In contrast
      to the sophisticated and cumbersome isolation procedures, even non-specialized
      laboratories could use this assay system for investigating clinical samples of
      different origin for C. burnetii within a short period of time.

PMID- 1397226
TI  - Molecular epidemiology of nasopharyngeal corynebacteria in healthy adults from an
      area where diphtheria vaccination has been extensively practiced.
AB  - In addition to conventional biochemical tests, a DNA probe specific for
      Corynebacterium diphtheriae was used to characterize 53 cystinase-positive and
      urease-negative corynebacteria strains isolated from pharyngeal and nasal swabs
      obtained from 515 healthy adults living in an urban area of central Italy. No
      Corynebacterium diphtheriae strain was found. Six "atypical" strains were
      isolated, which could not be classified in any of the species so far defined in
      the Corynebacterium genus. These strains appeared to be biochemically close to
      Corynebacterium pseudodiphtheriticum and genetically close to Corynebacterium
      diphtheriae, since their DNAs strongly hybridized, under relatively low
      stringency conditions, with a Corynebacterium diphtheriae-specific probe and
      since insertion sequences which are usually found in Corynebacterium diphtheriae
      genomes were also found to be present in their genomes. No one of these six
      strains was either toxigenic or susceptible to lysogenization by beta-corynephage
      carrying the tox gene. Therefore, they do not seem to have any epidemiological
      relevance as possible hosts for beta-phages.

PMID- 1397228
TI  - Evidence of the presence of spotted fever group rickettsiae in dogs and dog ticks
      of the central provinces in Spain.
AB  - To assess canine exposure to spotted fever group rickettsiae in the central
      provinces of Spain, ticks removed from dogs were studied by immunofluorescence
      (IF) staining. Twenty-eight out of 65 (43.0%) samples from ticks were positive.
      Sera from 58 dogs were also collected and the presence of antibodies to
      Rickettsia conorii studied. Thirty-four (58.6%) dogs presented significant titers
      by IF. Surveillance data from these provinces show the presence of Boutonneuse
      fever cases during recent years, evidence that dogs could serve as an indicator
      of rickettsial activity in these areas.

PMID- 1397229
TI  - An AIDS model with distributed incubation and variable infectiousness:
      applications to i.v. drug users in Latium, Italy.
AB  - An AIDS model with distributed incubation and variable infectiousness is
      considered and simulated via a second-order numerical method. The method is
      applied to the HIV epidemic among IV drug users in the Latium region of Italy,
      using available data on the length of the incubation period before the onset of
      AIDS, on the infectivity of infected individuals during that period, and on the
      demography of drug users. The contact rate is adjusted to match the actual number
      of AIDS cases. The sensitivity of the model to uncertainties in the parameters is
      finally investigated, by performing several simulations.

PMID- 1397230
TI  - Iron miners--a ten year follow-up.
AB  - 1167 workers of Lorraine (France) iron mines, a random sample of 5600 workers
      aged 35 to 55 years, at work in 1975 constituted the initial cohort that was
      examined twice at 5-year intervals after the first examination. A questionnaire
      on respiratory symptoms and smoking habits (MRC questionnaire) plus questions on
      the work history of each participant was completed, vital capacity (VC), forced
      expiratory volume in one second (FEV1.0), residual volume (RV) and fractional
      uptake of CO (FuCO) were measured at the first examination and repeated five and
      ten years later. At the end of the ten year follow-up, 522 subjects were re
      examined, 186 were lost to follow-up, 328 answered a mail questionnaire, and 111
      had died. The total number of deaths was not different from that of the general
      population, but for lung cancer the standardized mortality ratio (SMR) was
      significantly increased (SMR = 3.7). For the miners re-examined, frequency of
      bronchitis and decrease of functional tests were more related to age and smoking
      habits than to occupation.

PMID- 1397231
TI  - Progetto ATENA, a study on the etiology of major chronic diseases in women:
      design, rationale and objectives.
AB  - In spite of their important impact on populations, a number of diseases--all
      types of cancer and coronary heart disease in women--are "rare" events for
      statistical analysis and often analyzed in designs affected by selection and
      information biases, such as case-control studies. Large cohort studies based on
      the storage of biological specimens appear to be the most suitable solution for
      identifying risks for those diseases. Progetto ATENA, a study on the etiology of
      major chronic diseases in women is based on this design. Ten thousand women, aged
      30-69 years, living in the area of the city of Naples, free of cancer and
      cardiovascular disease, are being recruited over a four-year period. Ten per cent
      of the cohort is being randomly selected from the electoral roles, the rest will
      be volunteers. Information on dietary habits, reproductive history, familiarity
      for chronic disease, active smoking habits and passive smoking exposure, physical
      activity, and socio-demographic data are being collected. Clinical data such as
      blood pressure, anthropometry, and electrocardiogram are also taken. All the
      participants provide biological samples of blood (fasting drawing) and urine
      (timed morning spot). The biological samples are processed in order to explore
      the main areas under study (nutritional markers, metabolism, endocrinology,
      genetics, environmental exposure markers, thrombogenesis). The samples are stored
      in liquid nitrogen (-196 degrees C) as soon as the blood and urine processing
      have been finished. An appropriate follow-up information system on the health
      status of the participants is being set up to estimate incidence and mortality
      rates.

PMID- 1397233
TI  - Epidemiologic surveys of dog and cat bites in the Lyon area, France.
AB  - The urban pet population has increased considerably in France during the last
      twenty years. Two main questions need to be answered regarding rabies and other
      bite transmitted zoonoses: What is the actual incidence rate of dog and cat bites
      in an urban area; and how sensitive is the animal bite reporting system? To
      answer these questions, four surveys were conducted in the Lyon area, France, in
      1989: 1) an analysis of the consultation reports to the Pasteur Institute and of
      the bite reports sent by veterinarians to the local veterinary services for 1987
      and 1988; 2) a survey of 10 veterinary clinics located in the Lyon area and an
      analysis of their bite reports for the period May 1987-April 1989; 3) a
      questionnaire survey to 175 clients of these veterinary clinics; 4) a street
      survey of a random sample of the Lyon adult population (310 questionnaires). Bite
      incidence rates ranged from 10/100,000 persons/year for rabies post-exposure
      treatments to 37.5/100,000 persons/year for reported bites. However, less than
      half of the bite reports from the ten veterinary clinics were submitted to the
      veterinary services. The surveys conducted among pet owners and the general
      population indicated that, overall, bites were common events (3.4%) and occurred
      more often in pet owners (8.6%). In 74% of the cases, victims belonged to the pet
      owner's family and one fourth of the accidents occurred when playing with the
      pet. However, 12% of the accidents resulted from apparently unprovoked
      aggressions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397232
TI  - A study of the incidence of urogenital Chlamydia trachomatis in patients
      attending specialized departments of Rome, Milan and Turin, Italy.
AB  - A study of Chlamydia trachomatis was conducted in 5270 subjects seen at clinics
      of the Faculty of Medicine and Surgery at La Sapienza University in Rome, the S.
      Anna Hospital in Turin, and the Provincial Maternity Hospital Institute in Milan.
      In these areas, C. trachomatis was present in 5.8% of the cases examined; in
      addition it was present with statistically significant frequencies in cases of
      salpingitis (49.1) and epididymitis (21.7). It may also be found in cases of
      extrauterine pregnancy, sterility and abortion. Those most affected were women
      who had begun their sexual activity at an early age, were under 25, had several
      sexual partners and who used the coil and/or spermicides. A routine check for C.
      trachomatis should be considered for those women with those risk factors.

PMID- 1397234
TI  - The third epidemiological revolution.

PMID- 1397235
TI  - Urease production in Vibrio parahaemolyticus: a potential marker for virulence.

PMID- 1397236
TI  - Evaluation of bone marrow cellularity by magnetic resonance imaging in patients
      with myelodysplastic syndrome.
AB  - Magnetic resonance imaging (MRI) is a safe modality for examining the bone marrow
      and it is quite effective in revealing marrow involvement in hematological
      malignancies. MRI has been compared with needle marrow biopsy in 22 patients with
      myelodysplastic disorders. A fairly good concordance has been demonstrated in 79%
      of cases. However, in 5 patients MRI revealed that bone marrow hyperplasia was
      not generalized. Therefore in elderly patients with MDS, MRI of the spine allows
      the quantification of bone marrow hyperplasia with a greater accuracy than bone
      marrow biopsy and this may be useful for monitoring the effect of cytostatic
      treatment.

PMID- 1397237
TI  - Extramedullary progression of multiple myeloma following GM-CSF treatment-
      grounds for caution?

PMID- 1397238
TI  - Platelet activation by antiplatelet autoantibodies in immune thrombocytopenic
      purpura.

PMID- 1397239
TI  - Effectiveness of partial splenic embolization as treatment for hypersplenism in
      thalassaemia major: a 7-year follow up.
AB  - Partial splenic embolization is an alternative procedure to total splenectomy in
      patients with hypersplenism, and was performed in 10 patients with beta
      thalassaemia major who were then followed for 5 to 7 years. The results were
      compared with those of a 7-yr follow-up of 6 splenectomized thalassaemics. The
      blood consumption decreased and the leucocyte counts increased in both groups of
      patients. However, after partial splenic embolization, severe thrombocytosis-
      which is typical of splenectomized patients--did not develop and there were no
      severe complications from the operation, such as infections or reappearance of
      hypersplenism. In addition, the minor surgical injury and avoidance of abdominal
      scars were further advantages of partial splenic embolization over total
      splenectomy.

PMID- 1397240
TI  - Treatment of acute lymphoblastic leukaemia (ALL).
AB  - Forty-six consecutive patients with acute lymphoblastic leukaemia (ALL), having a
      median age of 23 years (range 14 to 64), underwent induction and consolidation
      chemotherapy with weekly parenteral vincristine, adriamycin, l-asparaginase and
      daily oral prednisone (VAAP), followed by standard central nervous system (CNS)
      prophylaxis. Maintenance therapy was given for 3 years and consisted of daily 6
      mercaptopurine, weekly methotrexate, and monthly intrathecal chemotherapy, with
      drug intensification comprising either vincristine, adriamycin and l-asparaginase
      (VAA) or cyclophosphamide, vincristine, cytosine arabinoside and prednisone
      (COAP). Complete remission (CR) was achieved in 36 patients (78%) and only the
      FAB L1 morphology was a significant predictive factor (Chi-squared = 3.91: p <
      0.05). Eight of the 10 non-responders had significant drug resistance and 3
      deaths were associated with marrow hypoplasia. Median follow-up is 52 months.
      Median duration of CR is 28 months, median survival of all patients is 16 months,
      and for those who achieved CR is 44 months. There was no difference between the
      two maintenance arms. Significant prognostic factors for survival are French
      American-British (FAB) subtype, in which the L1 is better than L2 (p = 0.05), and
      age (p = 0.035). Nineteen patients have experienced medullary relapse and 7 (37%)
      achieved subsequent CR; this is durable in a single patient who underwent
      allogeneic bone marrow transplantation. Eight patients (17%) had CNS disease at
      diagnosis; 5 achieved CR and 1 is alive and disease-free at 65+ months. There has
      been 1 CNS relapse. These results demonstrate that prolonged remissions and
      survival can be achieved with this protocol and many patients possibly cured. The
      level of toxicity is acceptable and the pattern of induction failure indicates
      that a margin exists for intensifying chemotherapy and thereby possibly further
      improving results.

PMID- 1397241
TI  - Erythropoietin response in anaemic patients with multiple myeloma and other
      lymphoid malignancies infiltrating the bone marrow.
AB  - Immunoreactive erythropoietin levels were measured in 42 patients with lymphoid
      malignancies with anaemia and bone marrow involvement. Results were compared to a
      control group of 16 patients suffering from anaemia due to other causes.
      Significant inverse correlations between serum erythropoietin level and
      haemoglobin concentration were shown for the patients with lymphoid malignancies
      and also for the control subjects. Overall, the erythropoietin levels of patients
      with lymphoid malignancies with bone marrow infiltration and with normal renal
      function did not differ significantly from erythropoietin levels of the anaemic
      controls. We conclude that anaemia in patients with lymphoproliferative disorders
      with bone marrow infiltration and normal renal function is caused primarily by a
      diminished/inadequate response to erythropoietin at the level of the target cell.

PMID- 1397243
TI  - Initial cytoreduction by mitoxantrone and cytarabine has no impact on the outcome
      of interferon-alfa-2b therapy in chronic myelogenous leukemia.
AB  - Eleven previously untreated patients with chronic-phase Philadelphia-chromosome
      positive chronic myelogenous leukemia were treated with cytotoxic chemotherapy
      followed by interferon-alfa-2b (IFN-alpha) maintenance. Initial chemotherapy
      consisted of three cycles of mitoxantrone 10 mg/m2 on day 1 and 2, and cytarabine
      100 mg/m2 daily for 5 d. Complete hematological response was obtained in 9 (82%)
      patients with moderately associated toxicity. However, cytogenetic responses
      after three cycles were poor and transient (1 partial suppression and 2 minor
      suppression of Ph chromosome). Maintenance therapy with IFN-alpha was started in
      10 patients at 5 x 10(6) U/m2 daily with dose reduction if hematologic toxicity
      or severe side-effects occurred. Of 9 evaluable patients treated for more than 3
      months, 6 patients maintained a complete hematological response, whereas 1
      patient remained in partial remission and 2 patients showed progressive disease.
      Cytogenetic evaluation showed partial suppression of Ph chromosome in 1 patient,
      whereas 1 patient had a minor response and 5 patients had no change or evolution
      of new chromosome abnormalities. As the results are not superior to IFN-alpha
      treatment alone, it is concluded that initial cytoreduction by mitoxantrone and
      cytarabine has no impact on the outcome of therapy in CML.

PMID- 1397242
TI  - Incidence of thrombotic complications in adult patients with acute lymphoblastic
      leukaemia receiving L-asparaginase during induction therapy: a retrospective
      study. The GIMEMA Group.
AB  - The incidence of thrombotic complications chronologically related to L
      asparaginase administration is retrospectively analyzed in 238 adult ALL patients
      treated according to the GIMEMA protocol ALL 0288. The patients (126 males and
      112 females, aged 12-68 years, median 29) received E. coli L-asparaginase (L-ase)
      in the induction phase at a dosage of 6000 U/m2/day x 7 d starting on d 15, as
      well as vincristine, prednisone, daunorubicin and cyclophosphamide, the last
      named by random 1:1. Ten patients (4.2%) developed thrombotic complications 5-15
      d (median 11 d) after the start of L-ase treatment. The thrombotic events, which
      were lethal in 5 patients, involved the cerebral sinus (5 cases), the cerebral
      arteria (2 cases), the portal vein (1 case), the pulmonary district (1 case), and
      a deep vein in the lower extremity (1 case). The occurrence of these
      complications was not related to the general thrombotic risk factors, nor to the
      main clinical and laboratory data registered at diagnosis and immediately before
      the start of L-asparaginase treatment. The present study documents for the first
      time in a sufficiently large series of adult ALL patients that the incidence and
      the severity of thrombotic events related to L-ase administration are relevant
      and need further consideration.

PMID- 1397244
TI  - A randomized trial comparing the use of fresh and stored platelets in the
      treatment of bone marrow transplant recipients.
AB  - Patients undergoing allogeneic bone marrow transplantation (BMT) were randomized
      into two groups. One group (n = 21) received single donor platelet concentrates
      (PC) that were as fresh as possible, the other group (n = 18) received single
      donor PC stored for 2 to 5 days. Actual mean storage times for PC were 1.12 +/-
      1.25 (mean +/- SD) and 2.67 +/- 1.30 d, respectively (p < 0.001). The total need
      for platelets during 60 d after BMT in patients receiving fresh PC was 22.1 +/-
      17.8 x 10(9) platelet/liter blood volume/d, and for stored PC 29.2 +/- 19.2 x
      10(9) platelets/liter blood volume/d (n.s.). A multiple regression analysis of
      the data showed no correlation between PC storage time and the PC requirement (p
      = 0.85). Posttransfusion corrected count increment (CCI) at 1 hour was 10.4 +/-
      5.1 for PC stored 0-1 d, 10.3 +/- 7.0 for PC stored 2-3 d, and 11.4 +/- 9.2 for
      PC stored 4-5 d. The corresponding CCI, at 18 h were 6.5 +/- 4.4, 5.4 +/- 3.3 and
      6.8 +/- 4.6. We conclude that there is no major difference between fresh and
      stored single donor PC.

PMID- 1397246
TI  - Multiple myeloma: intensified maintenance therapy with recombinant interferon
      alpha-2b plus glucocorticoids.
AB  - Interferon-alpha-2b has been demonstrated to prolong remission duration and
      survival in responding multiple myeloma patients. The aim of this study was to
      evaluate intensification of this maintenance therapy through the addition of
      glucocorticoids. Eighteen myeloma patients at diagnosis received six-12 courses
      of conventional chemotherapy and then interferon + glucocorticoids. This
      treatment included 3 megaunits of interferon three times a week, plus 4 days of
      pulsed high-dose dexamethasone (40 mg/d for 4 d every 28 d for 6 months/year) in
      patients < 70 yr old, or oral prednisone (50 mg three times a wk) in patients >
      70 yr old. Conventional chemotherapy induced an objective response in 13/18
      patients and a further reduction of the M component (> 50%) was achieved during
      interferon + glucocorticoids treatment in 7/13. 4/18 patients relapsed with a
      median follow-up of 22 months (range 13-40). These findings indicate that
      interferon + glucocorticoids, after inductional chemotherapy, further reduces
      tumor burden and may prolong remission.

PMID- 1397247
TI  - Elastase activity in leukaemic cells and plasma in patients with acute leukaemia.
AB  - Proteolysis of coagulation factors and inhibitors resulting in haemorrhage can be
      mediated by elastase. Indirect signs of this are elevated levels of elastase
      complexed to its inhibitor in plasma, alpha 1-antitrypsin (E alpha 1-AT). We have
      measured intracellular elastase activity in leukaemic cells from 60 patients with
      acute leukaemia. Elastase activity was detected in 92% of the patients with acute
      nonlymphoblastic leukaemia (ANL), no activity was found in the patients with
      acute lymphoblastic leukaemia (ALL). High levels were found in cells from
      patients with promyelocytic leukaemia. Moderate to high total circulating blast
      elastase activity was measured in 70% of the ANL patients with haemorrhage
      compared with 36% of the patients without bleeding complications (p < 0.05). The
      available intracellular elastase activity was correlated to the level of E alpha
      1-AT (rs = 0.42, p < 0.01) but not to the elastase specific split product of
      fibrinogen, B beta 30-43. In complete remission the levels of E alpha 1-AT were
      normalized. Intracellular elastase activity might be a useful supplement to
      differentiate ANL and ALL.

PMID- 1397249
TI  - The reflexive loop of past, present, and future in systemic therapy and
      consultation.
AB  - Time is one of the most basic social constructions. There are several different
      "times" (individual, social, cultural). This article deals with the time variable
      in systemic therapy--a most important variable, but often underestimated by
      therapists--and seeks to illustrate, with clinical examples, the peculiar
      interplay of past, present, and future in the therapy session. The co-creation of
      the past and future in the therapeutic system is also considered, together with
      the different temporal horizons of the family therapist and the observation team.
      In our view, time is one of the key issues in successful therapy: consideration
      of time can open new perspectives in both therapy and research.

PMID- 1397245
TI  - Erythrocyte pyruvate kinase deficiency: relations of residual enzyme activity,
      altered regulation of defective enzymes and concentrations of high-energy
      phosphates with the severity of clinical manifestation.
AB  - The defective enzymes of 54 patients with pyruvate kinase (PK) deficiency were
      characterized according to the recommendations of the International Committee for
      Standardization in Haematology (ICSH). The erythrocyte PK activity in whole blood
      was calculated considering the 16-fold higher activity of the reticulocyte enzyme
      (AR) compared to the erythrocyte enzyme (AE). The following parameters turned out
      to give a good correlation to the degree of haemolytic anaemia and can therefore
      serve as a prognostic tool: All patients with a severe course of the disease had
      residual erythrocyte PK activities less than 33% of the normal enzymes
      (percentage activity), and patients with mild haemolytic anaemia exhibited
      residual activity values below and above this threshold value. Studies of enzyme
      cooperative showed that positive cooperative or mixed cooperative
      phosphoenolpyruvate (PEP) binding with a predominant positive cooperative part
      appeared in all cases with a mild clinical course, and about one-third of the
      severe ones. Negative cooperativity or mixed cooperativity with predominant
      negative cooperative part was observed only with severe haemolytic anaemia.
      Furthermore, the determination of glucose-6-phosphate (G-6-P) turned out to be a
      good prognostic criterion, i.e. all patients with mild clinical course exhibited
      G-6-P-concentrations lower than 0.11 mumol/l red blood cells. In the case of
      patients with severe haemolytic anaemia, about 80% showed values higher than 0.11
      mumol/l RBC.

PMID- 1397248
TI  - Cultural and integrative therapy issues in the treatment of a Jamaican woman with
      panic disorder.
AB  - This article examines the treatment of a Jamaican woman with panic disorder, with
      a specific focus on the role of culture and the use of multiple formulations of
      the clinical problem. The work suggests that complex decisions are sometimes
      called for in assessing whether treatment should advocate against a cultural norm
      of the clients. The work further suggests that conceptualization of the problem
      from the vantage point of multiple frameworks is warranted in some instances, but
      that it requires considerable thought in order to achieve an integrated, coherent
      treatment plan.

PMID- 1397250
TI  - In-home treatment of families with seriously disturbed adolescents in crisis.
AB  - This article describes an innovative Adolescent In-Home Treatment Program that
      was designed as a hospital alternative for families with adolescents in serious
      crises. Using multiple-impact, in-home, and in-office techniques, a mental health
      team systemically intervenes with families to assist them in resolving this major
      developmental event. Since the program's inception, over 160 high-risk
      adolescents have completed the 90-day course of treatment. Preliminary data
      gathered from an early group of families and clinicians suggest the potential of
      significant improvements in family and adolescent functioning, and the attainment
      of clinical goals among the majority of families served.

PMID- 1397251
TI  - Dimensions of family rituals across two generations: relation to adolescent
      identity.
AB  - Family rituals are considered part of a generational process that fosters a sense
      of identity for individual members and is reflective of the family's shared
      belief system. The symbolic significance attached to family rituals is considered
      central to the force of family rituals. Three questions were addressed in the
      study: (1) Are the dimensions of family rituals viewed similarly across
      generations?; (2) Is level of ritualization related to adolescent identity?; (3)
      If there is disagreement about the relative level of ritualization in a family,
      is there a negative relation to adolescent identity? A total of 77 families with
      an adolescent member completed the Family Ritual Questionnaire, and the
      adolescents completed a measure of self-esteem. Results of a factor analysis
      demonstrated shared representation of family rituals across two generations, with
      one factor loading on the symbolic qualities of family rituals and the second
      factor loading on the routine aspects of family rituals. Positive relations were
      found between adolescent identity and the family's report of symbolic
      significance and affect associated with family rituals. A negative relation was
      found between mother-adolescent disagreement about family rituals and adolescent
      feelings of belonging. Distinguishing between meaning and routine aspects of
      family rituals is discussed as well as clinical implications.

PMID- 1397252
TI  - Expressed emotion in depressed patients and their partners.
AB  - This study was designed to assess the expressed emotion (EE) status in the
      spouses of depressed patients and the patients themselves, to relate the EE
      status to the severity of depression as measured by the Beck Depression Inventory
      (BDI), and to compare the prevalence of high EE between the target and control
      group. Seventeen depressed patients and their spouses, and 20 control couples
      participated in the study. The Five-Minute Speech Sample was used to assess the
      EE status. High EE was significantly more common in spouses of depressed patients
      and the patients themselves than in controls. There was a significant
      relationship between the EE status of the patients and their spouses. High EE in
      the patient and in the spouse corresponded significantly with a high BDI score of
      the patient. These findings underline the importance that in EE research the
      patients' EE status as well as their present mental health state must also be
      taken into account.

PMID- 1397253
TI  - Therapists' ratings of fundamentalist and nonfundamentalist families in therapy:
      an empirical comparison.
AB  - Using the Family Health Scale, Part I of an instrument developed for this study,
      two randomly selected groups of certified family therapists rated either
      nonfundamentalist or fundamentalist families in therapy on eight recognized
      indicators of family health. Factor analysis yielded eight factors accounting for
      66% of the variance between groups. Cannonical discriminant function analysis
      revealed that therapists rated fundamentalist families as significantly less
      healthy on three of the eight factors and more healthy on one factor. Part II of
      this instrument, the Religion Impact Scale assessed the effects of church
      community and church teachings upon families. For fundamentalists, the church and
      concomitant belief system had a significant impact upon family organization and
      functioning. Theoretical and clinical implications of these findings are
      discussed.

PMID- 1397255
TI  - Do cultures clarify models or do models clarify cultures?

PMID- 1397254
TI  - Truth in [sic] consequences.

PMID- 1397256
TI  - The inverted hexagonal phase is more sensitive to hydroperoxidation than the
      multilamellar phase in phosphatidylcholine and phosphatidylethanolamine aqueous
      dispersions.
AB  - The effect of phase behaviour (hexagonal II phase and lamellar phase) on the
      peroxidation of membrane phospholipids has been investigated in dilinoleoyl
      phosphatidylcholine (DLPC)/dilinoleoyl phosphatidylethanolamine (DLPE) aqueous
      dispersions. Peroxidation was initiated with a water-soluble radical inducer 2,2'
      azobis (2-amidino-propane) dihydrochloride (AAPN). The phospholipid morphology
      was monitored by 31P-nuclear magnetic resonance (NMR). Phospholipid
      hydroperoxides (PCOOH and PEOOH) were determined by chemiluminescence high
      performance liquid chromatography (CL-HPLC). In pH-induced phase transition
      systems, DLPE in the bilayer state was much less oxidized than in the hexagonal
      II state. In composition-induced phase transition systems, the formation of total
      hydroperoxides and the consumption of alpha-tocopherol in the hexagonal II phase
      were greater than in the bilayer phase. These data suggest that the hexagonal II
      phase is more sensitive to hydroperoxidation than the bilayer phase in
      phospholipid aqueous dispersions.

PMID- 1397257
TI  - RNA editing of atp6 transcripts from male-sterile and normal cytoplasms of
      rapeseed (Brassica napus L.).
AB  - The complete cDNA sequence corresponding to the rapeseed atp6 gene transcript
      (coding for subunit 6 of F0-ATPase) has been determined by a method involving
      cDNA synthesis, using specific oligonucleotides as primers, followed by PCR
      amplification, cloning and sequencing of the amplification products. Only one
      modification, a C-to-U conversion, has been found when compared to the genomic
      mitochondrial DNA sequence. Comparison of the extent and frequency of RNA editing
      of the pol cytoplasmic male sterile (cms) atp6 transcript with those of normal
      atp6 transcript indicates that there is no variation between the editing status
      of the atp6 transcripts from pol cms and normal cytoplasms.

PMID- 1397258
TI  - Localization of the steroid-binding site of the human sex steroid-binding protein
      of plasma (SBP or SHBG) by site-directed mutagenesis.
AB  - The amino-terminal region of the human sex steroid-binding protein of plasma (SBP
      or SHBG) containing K134 and M139 was found to represent part of the steroid
      binding site. This was accomplished by constructing and expressing site-directed
      mutants having the following replacements: M139L, M139K, M139S, K134A, H235S, and
      Y57F. The results indicated that M139L and H235S were fully-active, K134A and
      Y57F were 50 and 67% active, M139K was 7% active, and M139S was inactive. These
      results support affinity-labeling data indicating that both K134 and M139 are
      located in or near the site, and suggest that Y57 may play a role in steroid
      binding. The fully active H235S mutant reveals that H235 is not involved in the
      steroid-binding process.

PMID- 1397259
TI  - The 26 S proteasome is activated at two points in the ascidian cell cycle.
AB  - The proteasome undergoes cell cycle-dependent changes in its subcellular
      distribution during ascidian embryonic development [(1992) Dev. Biol. 151, 27
      33]. In this study, we demonstrate that the 26 S proteasome is markedly activated
      in both prophase and metaphase of the mitotic cell cycle in the ascidian embryos
      in comparison with the case of the 20 S proteasome. These results suggest that
      the 26 S proteasome is activated and participates in proteolysis at the
      restricted stages of the cell cycle.

PMID- 1397260
TI  - Fc epsilon receptor mediated Ca2+ influx into mast cells is modulated by the
      concentration of cytosolic free Ca2+ ions.
AB  - The relationship between the Fc epsilon receptor mediated stimulation of mast
      cells and the Ca2+ signal it induces were studied using thapsigargin (TG), a
      blocker of the endoplasmic reticulum Ca2+ pump. TG induced, in mucosal mast cells
      (RBL-2H3 line), a dose-dependent and an InsP3-independent increase in [Ca2+]i
      (from resting levels of 83-150 nM to 600-680 nM), and a secretory response
      amounting to 30-50% of that observed upon Fc epsilon RI clustering. The TG
      induced rise of [Ca2+]i is most probably provided by both arrest of its uptake by
      the endoplasmic reticulum and influx from the medium. Thus, Ca2+ influx in mast
      cells may be modulated by the [Ca2+]i level.

PMID- 1397261
TI  - Regulatory light-chain Cys-55 sites on the two heads of myosin can come within 2A
      of each other.
AB  - The di-thiol reagent, 5,5'-dithiobis (2-nitrobenzoic acid) is shown to induce
      disulfide bond formation between Mercenaria regulatory light-chain Cys-55 sites
      on either head of scallop hybrid myosin. This indicates that these two sites on
      opposite heads of myosin can come within 2A of each other and this confirms a
      prediction based on earlier data [Chantler, Tao and Stafford (1991) Biophys. J.
      59, 1242-1250]. Results demonstrate that myosin heads in solution show a
      considerable mutual freedom of movement which can be monitored by probes in the
      vicinity of regulatory light-chain residue 55. Implications for light-chain
      movement on the myosin head are discussed.

PMID- 1397262
TI  - Involvement of DNA polymerase beta in proliferation of rat liver induced by lead
      nitrate or partial hepatectomy.
AB  - We have studied the expression pattern of DNA polymerase beta in two different
      models of in vivo cell proliferation. Both mRNA levels and enzyme activity of DNA
      polymerase beta markedly increased before and/or during DNA synthesis in
      proliferating hepatocytes in mitogen-treated and partially hepatectomized rats.
      The time-courses of the expression of the gene coding for DNA polymerase beta
      were significantly different in the two cell systems. A 5-fold increase in DNA
      polymerase beta mRNA was observed 8 h after lead nitrate administration, i.e.
      well before the onset of DNA synthesis. In the regenerative liver cells a 3-fold
      increase in the amount of mRNA was observed 24-48 h after partial hepatectomy,
      the event being coincident with extensive DNA synthesis. In both systems, the
      increase of mRNA levels was always paralleled by an increase in enzyme activity,
      suggesting that DNA polymerase beta activity may be regulated at a pre
      translational level.

PMID- 1397263
TI  - Selective binding of anchorin CII (annexin V) to type II and X collagen and to
      chondrocalcin (C-propeptide of type II collagen). Implications for anchoring
      function between matrix vesicles and matrix proteins.
AB  - Anchorin CII is a collagen binding protein of the annexin family associated with
      plasma membranes of chondrocytes, osteoblasts, and many other cells. As a major
      constituent of cartilage-derived matrix vesicles it has been shown to bind to
      native type II and X collagen. In accordance with this observation, here we show
      the localization of anchorin CII in the extracellular matrix of calcifying
      cartilage in the fetal human growth plate, and that it was restricted to the
      chondrocyte surface in proliferating and resting cartilage. Furthermore, we
      present evidence, using a slot blot assay, that anchorin CII not only binds to
      native type II and X collagen, but also to chondrocalcin, the carboxy-terminal
      extension of type II procollagen, in a calcium-independent manner. Pepsin
      digestion of type II collagen results in loss of anchorin CII binding, confirming
      our previous notion that the telopeptide region of type II collagen carries
      anchorin CII binding sites.

PMID- 1397264
TI  - Simultaneous synthesis of enzymatically active luciferase and biologically active
      beta subunit of human chorionic gonadotropin in caterpillars infected with a
      recombinant baculovirus.
AB  - The beta subunit of human chorionic gonadotropin (beta hCG), a secretory and
      extensively glycosylated hormone, and firefly luciferase, a non-secretory enzyme,
      were simultaneously synthesized in Spodoptera larvae upon infection with a dual
      expression recombinant baculovirus, vAc beta hCG-luc. Luciferase was retained
      predominantly in the body tissue while beta hCG was secreted into the hemolymph
      of infected larvae. Both the proteins were similar to their authentic
      counterparts in terms of immunoreactivity and bioactivity. The caterpillar
      derived recombinant hCG exhibited reduced electrophoretic mobility on SDS-PAGE
      and increased biological activity as compared to the hCG expressed in insect
      cells in culture. The implications of using the larval system for expressing an
      extensively glycosylated protein are discussed.

PMID- 1397265
TI  - The purification and amino acid sequences of four Tx2 neurotoxins from the venom
      of the Brazilian 'armed' spider Phoneutria nigriventer (Keys).
AB  - Four neurotoxic polypeptides (Tx2-1, Txt2-5, Tx2-6 and Tx2-9) were purified from
      the venom of the South American 'armed' spider Phoneutria nigriventer (Keys) by
      gel filtration and reverse phase FPLC and HPLC. These cysteine-rich polypeptides
      exhibited different levels of neurotoxicity in mice after intracerebroventricular
      injection. Tx2-1, Tx2-5 and Tx2-6 caused spastic paralysis and death, but the
      less toxic Tx2-9 produced only tail erection and scratching. The molecular
      weights of the polypeptides as determined by desorption mass spectroscoopy were
      5838.8 for Tx2-1, 5116.6 (Tx2-5), 5291.3 (Tx2-6) and 3742.1 (Tx2-9). The complete
      amino acid sequences of the neurotoxins were determined by automated Edman
      degradation and by manual DABITC-PITC microsequence analysis of peptides obtained
      after digestions with various proteases. The amino acid sequences of Tx2-1 (53
      residues), Tx2-5 (49 residues) and Tx2-6 (48 residues) were homologous, but had
      only limited similarities to the less toxic Tx2-9 (32 residues). All four
      polypeptides had varying sequence identities with other neurotoxins from
      different spider species and biologically active peptides from scorpions, a sea
      snail and seeds of Mirabilis jalapa.

PMID- 1397266
TI  - A new crystal form of the complex between seryl-tRNA synthetase and tRNA(Ser)
      from Thermus thermophilus that diffracts to 2.8 A resolution.
AB  - Two distinct complexes between seryl-tRNA synthetase and tRNA(Ser) from Thermus
      thermophilus have been crystallized using ammonium sulphate as a precipitant.
      Form III crystals grow from solutions containing a 1:2.5 stoichiometry of
      synthetase dimer to tRNA. They are of monoclinic space group C2 with unit cell
      dimensions a = 211.6 A, b = 126.8 A, c = 197.1 A, beta = 132.4 degrees and
      diffract to about 3.5 A. Preliminary crystallographic results show that the
      crystallographic asymmetric unit contains two synthetase dimers. Form IV crystals
      grow from solutions containing a 1:1.5 stoichiometry of synthetase dimer to tRNA.
      They are of orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions a =
      124.5 A, b = 128.9 A, c = 121.2 A and diffract to 2.8 A resolution. Preliminary
      crystallographic results show that these crystals contain only one tRNA molecule
      bound to a synthetase dimer.

PMID- 1397267
TI  - Cloning and sequencing of glutamate mutase component S from Clostridium
      tetanomorphum. Homologies with other cobalamin-dependent enzymes.
AB  - The gene encoding component S, the small subunit, of glutamate mutase, an
      adenosylcobalamin (coenzyme B12)-dependent enzyme from Clostridium tetanomorphum
      has been cloned and its nucleotide sequence determined. The mutS gene encodes a
      protein of 137 amino acid residues, with M(r) 14,748. The deduced amino acid
      sequence showed homology with the C-terminal portion of adenosylcobalamin
      dependent methylmalonyl-CoA mutase [1989, Biochem. J. 260, 345-352] and a region
      of cobalamin-dependent methionine synthase which has been shown to bind cobalamin
      [1989, J. Biol. Chem 264, 13888-13895].

PMID- 1397268
TI  - Phosphate derivatives of AZT display enhanced selectivity of action against HIV 1
      by comparison to the parent nucleoside.
AB  - Novel phosphate derivatives of the anti-HIV nucleoside analogue AZT have been
      prepared by phosphorochloridate chemistry. In particular, phosphates carrying
      ester-containing side-chains are described. These materials are designed to act
      as membrane-soluble pro-drugs of the bio-active free nucleotides. In vitro
      evaluation revealed the compounds to have a pronounced, selective antiviral
      activity. In several cases the phosphate derivatives are more selective in their
      action than the parent nucleoside AZT. In particular, this arises from the low
      toxicity of the phosphate pro-drugs by comparison to AZT. These data support the
      suggestion that the phosphate derivatives exert their biological effects via
      intracellular release of the nucleotide forms, and suggests that such pro-drug
      forms may be worthy of further study.

PMID- 1397269
TI  - De novo synthesis and desaturation of fatty acids at the mitochondrial acyl
      carrier protein, a subunit of NADH:ubiquinone oxidoreductase in Neurospora
      crassa.
AB  - We have cultivated the cel mutant of Neurospora crassa defective in cytosolic
      fatty acid synthesis with [2-14C]malonate and found radioactivity covalently
      attached to the mitochondrial acyl-carrier protein (ACP), a subunit of the
      respiratory chain NADH:ubiquinone oxidoreductase. We purified the ACP by reverse
      phase HPLC: the bound acyl groups were trans-esterified to methylesters and
      analyzed by gas chromatography. The saturated C6 to C18 fatty acids and oleic
      acid were detected. De novo synthesis and desaturation of fatty acids at the ACP
      subunit of NADH:ubiquinone oxidoreductase and use of the products of this
      mitochondrial synthetic pathway for cardiolipin synthesis is discussed.

PMID- 1397270
TI  - Glycogen metabolism in a Saccharomyces cerevisiae phosphoglucose isomerase (pgil)
      disruption mutant.
AB  - Disruption of the gene pgil of Saccharomyces cerevisiae, which codes for
      phosphoglucose isomerase, results in a dramatic increase in the amount of
      intracellular glycogen in early exponential cultures. The level of glucose 6
      phosphate was much higher in mutant than in wild-type cells. Phosphorylase a
      activity and the state of activation of glycogen synthase were also investigated.
      Phosphorylase a activity was rather low along the culture in wild-type cells,
      whereas it was consistently higher in mutants. Glycogen synthase was mostly in
      the active form in early-medium exponential cultures in wild-type cells whereas
      the activation state of this enzyme in mutant cells, although lower at the
      earlier steps of the culture, did not differ from wild-type cells at later
      stages. The fact that the intracellular levels of UDP-glucose are markedly
      increased in mutant cells suggest that the observed accumulation of glycogen
      results from a rise in substrate availability rather than from the activation of
      the enzyme responsible for the synthesis of the polysaccharide.

PMID- 1397272
TI  - Single cell observation of ligand-induced desensitization of B-cell membrane
      immunoglobulin-mediated calcium signals.
AB  - Using a digital imaging fluorescence microscope we have observed the membrane
      immunoglobulin (mIg)-induced desensitization of calcium signals in individual
      BAL17 B lymphoma cells which express two kinds of antigen receptors, mIgM and
      mIgD. The mIgD-mediated desensitization was partly abrogated by pretreating the
      cells with phorbol 12-myristate 13-acetate (PMA) for 24 h, however, the mIgM
      mediated one was not affected by the pretreatment. This supports the idea that at
      least two mechanisms are operative for mIg-induced desensitization in B cells.

PMID- 1397271
TI  - Modulation of rat liver peroxisomal and microsomal fatty acid oxidation by
      starvation.
AB  - In this work the microsomal lauric acid omega-hydroxylation, fatty acid
      peroxisomal beta-oxidation, and the levels of cytochrome P-450 IVA1 were studied
      in liver tissue from starved rats. Starvation increased the peroxisomal beta
      oxidation and the microsomal hydroxylation of fatty acids. The correlation
      between these activities would support the proposal that both processes are
      linked, contributing in part to catabolism of fatty acids in liver of starved
      rats.

PMID- 1397273
TI  - Cloning and sequence analysis of the phenylalanyl-trna synthetase genes (pheST)
      from Thermus thermophilus.

PMID- 1397274
TI  - Reversal of peptide backbone direction may result in the mirroring of protein
      structure.
AB  - In linear polypeptides, inversion of amino acid chirality (all-L to all-D)
      achieves a mirroring of side chain positions and interactions in conformational
      space. A similar mirroring of side chain positions is independently achieved by a
      reversal of the direction of the peptide backbone (retro modification). Thus,
      while an all-D chain could be expected to adopt a perfect 'mirror image' of the
      three-dimensional structure of its parent all-L protein, the retro-all-L chain
      could be expected to adopt a topological equivalent of such a mirror image,
      through the symmetry transformations of side chain interactions. These notions,
      supported by sequence analyses, modelling studies, and evidence relating to the
      activity of 'retro-inverso' peptides, are extended towards the proposal, that the
      backbone reversed chain of a large globular protein might recognize the chiral
      opposite of the parent protein's substrate(s).

PMID- 1397275
TI  - A mutant alpha-amylase with enhanced activity specific for short substrates.
AB  - The 210th lysine (K210) at the active site in Saccharomycopsis fibuligera alpha
      amylase was altered to arginine (R) or asparagine (N) by site-directed
      mutagenesis. Replacement of K210 by R strengthened the 7th and weakened the 8th
      subsite affinities. K210 was found to contribute to both the 8th and the 7th
      subsites. The catalytic activity of the K210R enzyme for the hydrolysis of
      maltose (G2) was three-times higher than that of the native enzyme due to an
      increase in the affinity of the 7th subsite adjacent to the catalytic site,
      whereas the activity of the K210N enzyme for G2 was decreased to 1% of that of
      the native enzyme by a reduction in the 7th subsite affinity.

PMID- 1397276
TI  - Novel ion channels in the protists, Mougeotia and Saprolegnia, using sub
      gigaseals.
AB  - Protoplasts of the filamentous alga, Mougeotia, and the filamentous fungal
      oomycete, Saprolegnia ferax, exhibit two K+ ion channels (2-6 pA) using the patch
      clamp technique when the seals are less than 1 G omega (about 100 M omega). The
      membrane potential of the protoplasts was near 0 mV as measured intracellularly
      with double-barreled micropipettes; thus, inward K+ flux is due solely to
      concentration differences. Although conductances are in the range expected for K+
      channels, the activity at 0 mV is not seen in other organisms under gigaseal
      conditions. This paper draws attention to the usefulness of this subsidiary patch
      clamp technique and the novel characteristics of ion channels in Mougeotia and
      Saprolegnia.

PMID- 1397277
TI  - Molecular basis for low temperature compartment formation by transitional
      endoplasmic reticulum of rat liver.
AB  - The molecular basis for temperature compartment formation was investigated using
      a cell-free system from rat liver. The donor was from liver slices prelabeled
      with [3H]acetate. Unlabeled Golgi apparatus membranes were immobilized on
      nitrocellulose as the acceptor. When transfer was determined as a function of
      temperature, a transition in transfer activity was observed at low temperatures
      (less than or equal to 20 degrees C) similar to that seen in vivo. The decrease
      in transfer efficiency correlated with a decrease in phosphatidylethanolamine and
      phosphatidylserine content of the transition vesicles formed. By adding lipid
      mixtures enriched in these lipids to the vesicles, their ability to fuse with the
      cis Golgi apparatus was reconstituted. These findings provide evidence for a role
      for lipids in low temperature compartment formation.

PMID- 1397278
TI  - Troponin replacement in permeabilized cardiac muscle. Reversible extraction of
      troponin I by incubation with vanadate.
AB  - Calcium-dependent regulation of tension and ATPase activity in permeabilized
      porcine ventricular muscle was lost after incubation with 10 mM vanadate. After
      transfer from vanadate to a vanadate-free, low-Ca2+ solution (pCa greater than
      8), the permeabilized muscle produced 84.8% +/- 20.1% (+/- S.D., n = 98) of the
      isometric force elicited by high Ca2+ (pCa approximately 4.5) prior to incubation
      with vanadate. Transfer back to a high Ca2+ solution elicited no additional force
      (83.2% +/- 18.7% of control force). SDS-PAGE and immunoblot analysis of fibers
      and solutions demonstrated substantial extraction (greater than 90%) of Troponin
      I (TnI). Calcium dependence was restored after incubation with solutions
      containing either whole cardiac troponin or a combination of TnI and troponin C
      subunits. This reversible extraction of troponin directly demonstrates the role
      of TnI in the regulation of striated muscle contractility and permits specific
      substitution of the native TnI with exogenously supplied protein.

PMID- 1397279
TI  - The cDNA structure of the porcine pro-hormone convertase PC2 and the comparative
      processing by PC1 and PC2 of the N-terminal glycopeptide segment of porcine POMC.
AB  - The complete cDNA structure of the porcine (p) pro-protein and pro-hormone
      convertase PC2 (pPC2) was obtained from a cDNA library of pituitary
      neurointermediate lobes mRNA. The deduced amino acid sequence revealed that pPC2
      exhibits a 99-97% sequence identity to the human, mouse and rat homologues. The
      3' end of the 2.1 kb cDNA is the least conserved segment. On Northern blots of
      pars intermedia poly A+ RNA two transcripts of 3 and 5 kb were detected.
      Molecular analysis of the N-terminal glycopeptide products of porcine pro
      opiomelanocortin (pPOMC) co-expressed with vaccinia virus recombinants of PC1 or
      PC2, revealed that in cells devoid or containing secretory granules both
      convertases can cleave pPOMC with PC1 releasing the 1-80, 1-107 and 1-148
      glycopeptide fragments, and PC2 cleaving pPOMC directly into pPOMC 1-107.

PMID- 1397280
TI  - Accumulation of protoporphyrin IX in light-sensitive mutants of Escherichia coli.
AB  - The accumulation of protoporphyrin IX (Proto IX) in light-sensitive mutants of
      Escherichia coli was detected by spectrofluorimetry. Fluorescence emission and
      excitation spectra were recorded from extracts of bacterial cells. Proto IX
      clearly accumulated in cells with mutations in the visA (hemH) gene but not in
      the wild-type strain CA274 or in visA mutants that had been rendered light
      resistant by introduction of the wild-type visA+ gene. Accumulation of Proto IX
      was also not observed in cells with a mutation in the visB gene. These results
      confirm the hypothesis that the sensitivity of the visA mutants to light is
      caused by the abnormal accumulation of Proto IX, a substrate of ferrochelatase,
      as the result of a genetic defect in the gene for ferrochelatase.

PMID- 1397281
TI  - Manganese deficiency and transcriptional regulation of mitochondrial superoxide
      dismutase in hepatomas.
AB  - The presumed involvement of the transition metals manganese and copper in the
      regulation of the expression of the Mn- and CuZn-containing superoxide dismutase
      genes has been investigated in normal and neoplastic tissues of the rat. Two
      hepatomas of the Morris line have been employed, the slow growing, highly
      differentiated 9618A and the fast growing, poorly differentiated 3924A. The data
      obtained indicate a control at the pretranslational level of the Mn-containing
      enzyme, presumably exerted by the manganese ion. The CuZn-containing superoxide
      dismutase is also regulated pretranslationally in the normal tissues examined and
      in the hepatoma 3924A. However, there is no indication for the involvement of the
      copper ion, which in the liver is mostly located in the cytosol bound to CuZnSOD,
      in such regulation. The possible role of a reduced redox state, concomitant to
      the manganese deficiency in hepatoma tissues, in the down regulation of Mn
      containing superoxide dismutase is discussed.

PMID- 1397282
TI  - Tyrosine phosphorylation is an early and requisite signal induced by interferon
      gamma in HL-60 cells.
AB  - Interferon-gamma (IFN gamma) is a potent immunomodulatory cytokine. However, the
      early mechanisms which mediate the pleiotropic effects of IFN gamma on different
      cells are as yet poorly understood. Therefore, we tested the role of tyrosine
      phosphorylation in signalling induced by IFN gamma. IFN gamma was found to induce
      rapid tyrosine phosphorylation of several proteins in HL-60 cells. This effect
      was detectable by 2 min, reached a maximum by about 4-16 min and thereafter
      declined. Tyrosine phosphorylation was dependent on receptor occupation and was
      maximally stimulated by 10 ng/ml IFN gamma. Treatment of HL-60 cells with the
      tyrosine kinase inhibitors, genistein and herbimycin A, inhibited both IFN gamma
      stimulated tyrosine phosphorylation and IFN gamma-induced Fc receptor expression.
      Thus, increased tyrosine phosphorylation appears to be an obligatory early and
      proximal signal mediating at least some of the later cellular responses induced
      by IFN gamma in HL-60 cells.

PMID- 1397283
TI  - Suppression of peroxisomal lipid beta-oxidation enzymes of TNF-alpha.
AB  - TNF-alpha is a potent cytokine which induces marked hyperlipidemia. Because of
      the important role of peroxisomes in lipid metabolism we investigated the effects
      of human recombinant TNF-alpha upon rat liver peroxisomal enzymes. Sixteen hours
      after the administration of a single dose of 25 micrograms of TNF-alpha to male
      rats the activity of peroxisomal fatty acyl-CoA oxidase was reduced by 50%. This
      was confirmed also by immunoblotting and by quantitative immunoelectron
      microscopy which in addition revealed substantial reduction of the trifunctional
      protein (hydratase-dehydrogenase-isomerase) in peroxisomes. These observations
      suggest that the suppression of peroxisomal beta-oxidation may contribute to the
      perturbation of the isomerase) in peroxisomes. These observations suggest that
      the suppression of peroxisomal beta-oxidation may contribute to the perturbation
      of the lipid metabolism induced by TNF-alpha.

PMID- 1397284
TI  - Protein-tyrosine kinase activity of alternate protein products of the Drosophila
      Dsrc28C locus.
AB  - The Dsrc28C gene is a unique member of the extensive tyrosine kinase family. Two
      proteins, p66Dsrc28C and p55Dsrc28C, are encoded by the gene. Each contains a
      highly conserved tyrosine kinase domain and each lacks the usual amino-terminal
      myristylation signal. The protein-tyrosine kinase activity of the two proteins
      was investigated through a recombinant baculovirus expression system. p66Dsrc28C
      expressed from a recombinant baculovirus phosphorylated a large number of Sf9
      cell proteins on tyrosine. A group of proteins of approximately 100 kDa were the
      preferred substrates. No evidence of p66Dsrc28C autophosphorylation was found. In
      contrast to p66Dsrc28C, p55Dsrc28C did not exhibit protein-tyrosine kinase
      activity when expressed from a recombinant baculovirus. A deletion derivative of
      p66Dsrc28C lacking the SH3 and SH2 domains also failed to phosphorylate Sf9 cell
      proteins. These results suggest that the protein-tyrosine kinase activity of
      Dsrc28C proteins is tightly regulated.

PMID- 1397286
TI  - Light-induced degradation of D2 protein in isolated photosystem II reaction
      center complex.
AB  - When isolated photosystem II reaction centers from spinach are exposed to
      photoinhibitory light in the presence of an electron acceptor, breakdown products
      of the D2 protein at 28, 25, 23, 18, 9, 5 and 4.5 kDa are detected by
      immunoblotting with a monospecific anti-D2 polyclonal antibody. In a time-course
      experiment the 23 and 4.5 kDa fragments show a transient appearance, whilst the
      others are photoaccumulated. The regions of the D2 protein containing the
      cleavage sites for the 28 and 18 kDa photoinduced fragments have been identified.
      Significant degradation of D2 takes place only in the presence of an electron
      acceptor, and breakdown of the protein is partially prevented by serine-type
      protease inhibitors.

PMID- 1397285
TI  - An endothelin B receptor-selective antagonist: IRL 1038, [Cys11-Cys15]-endothelin
      1(11-21)
AB  - In the inhibition of specific binding of [125I]endothelins (ETs) to membrane from
      various tissues of rats, guinea pigs, pigs and humans, [Cys11-Cys15]-ET-1(11-21),
      IRL 1038, has a much higher affinity for ETB receptors (Ki = 6-11 nM) than for
      ETA receptors (Ki = 0.4-0.7 microM). In contraction assays, with ET-3 as a
      stimulant, 3 microM IRL 1038 antagonized the ETB receptor-mediated contraction of
      guinea pig ileal and tracheal smooth muscle without any significant agonistic
      activity, but did not effect the ETA receptor-mediated contraction of rat aortic
      smooth muscle. IRL 1038 is therefore, considered to be the first antagonist
      selective to the ETB receptor.

PMID- 1397287
TI  - Transforming growth factor-beta 1 rapidly activates phosphorylase in a calcium
      dependent manner in rat hepatocytes.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) rapidly activated phosphorylase in
      isolated rat hepatocytes (half-maximal rate of activation with approximately 0.1
      ng/ml). Removal of Ca2+ from the external medium just before TGF-beta 1 addition
      markedly attenuated phosphorylase activation. TGF-beta 1 (1 ng/ml) produced a
      small increase in [Ca2+]i (approximately 10% increase after 30 s), which appears
      sufficient to account for phosphorylase activation. These observations indicate
      that activation of the TGF-beta 1 signal transduction system in hepatocytes is
      linked with a small increase in [Ca2+]i, and external Ca2+ may contribute in part
      to this increase.

PMID- 1397288
TI  - Okadaic acid and calyculin A enhance the effect of thyrotropin-releasing hormone
      on GH3 rat anterior pituitary cells excitability.
AB  - Thyrotropin-releasing hormone (TRH) causes a transient hyperpolarization followed
      by several minutes of increased action potential frequency in patch-perforated
      current-clamped GH3 cells. Treatment of cells for 5 min with either 2 or 100 nM
      of the protein phosphatase inhibitor okadaic acid does not affect electrical
      activity of the cells, but potentiates the enhancement of action potential
      frequency elicited by a subsequent addition of TRH. Alternatively, 100 nM (but
      not 2 nM) of okadaic acid added during the second phase of TRH action, further
      increases the frequency of firing above that produced by the hormone. Similar
      effects to those of 2 nM okadaic acid are observed with 20 nM calyculin A. These
      data suggest that a protein phosphatase plays a major role in regulating the
      delayed effects of TRH on cell excitability in GH3 cells.

PMID- 1397289
TI  - Cloning and sequencing of the cDNA encoding rice elongation factor 1 beta'.
AB  - A cDNA clone coding for rice elongation factor 1 beta' (EF-1 beta') was isolated
      from a rice anther cDNA library. The clone, named RB', was 980 bp long and
      contained a single open reading frame coding for 223 amino acids; the first 31
      amino acids, except for the first methionine, which is absent in the mature
      protein, are identical to those of the purified protein determined with a protein
      sequencer. The amino acid sequence of rice EF-1 beta' shows homology to the C
      terminal half of Artemia salina EF-1 beta (59%) and human EF-1 beta (63%), but
      might not have a phosphorylation site for casein kinase II which has been
      conserved in Artemia saline EF-1 beta and EF-1 delta, human EF-1 beta and
      silkworm EF-1 beta'.

PMID- 1397290
TI  - Evidence for a hydroxy-aluminium polymer (Al13) in synaptosomes.
AB  - The presence of the hydroxy-aluminium polymer (Al13-(OH)24O4(H2O)12(7+)) was
      noticed inside synaptosomes when synaptosomes were incubated with Al(NO3)3 at
      neutral pH values. Dysprosium nitrate (Dy(NO3)3)--a shift reagent--facilities the
      identification of the Al13 species distinctly inside the synaptosomes. 27Al NMR
      was used as a tool to detect the Al13 complex inside and outside the
      synaptosomes.

PMID- 1397291
TI  - Enzymatic and immunological detection of G protein alpha-subunits in the
      pathogenic fungus Candida albicans.
AB  - GTP stimulation of adenylyl cyclase from the dimorphic pathogenic fungus Candida
      albicans is greatly enhanced by preincubation of membrane proteins with cholera
      toxin, NAD and ATP. In the presence of [32P]NAD the toxin catalyzes the covalent
      incorporation of radioactivity into a membrane protein of 40 kDa. Pertussis toxin
      catalyzes the transference of the radioactivity from [32P]NAD to a 32 kDa
      protein. Two major proteins of 40-42 and 30-32 kDa can also be recognized in
      Western blots by an anti G alpha-common antibody. The results support the idea
      that G proteins are part of the hormone sensory transduction chain of Candida
      [(1990) Biochem. Biophys. Res. Commun. 167, 1177-1183].

PMID- 1397292
TI  - Processing of mutated proinsulin with tetrabasic cleavage sites to bioactive
      insulin in the non-endocrine cell line, COS-7.
AB  - The amino acid sequence, Arg-4-X-3-Lys/Arg-2-Arg-1 decreases X+1, is thought to
      be a consensus processing site for a constitutive secretory pathway in non
      endocrine cells. We created a mutant proinsulin DNA with a peptide structure of B
      chain-Arg-Arg-Lys-Arg-C peptide-Arg-Arg-Lys-Arg-A chain, which compares to the
      native proinsulin structure of B chain-Arg-Arg-C peptide-Lys-Arg-A chain. When
      the mutant insulin was expressed in a monkey kidney-derived cell line, COS-7,
      approximately 60% of the total immunoreactive insulin appeared as mature insulin
      in the culture medium. This conversion to the mature form was strikingly
      facilitated by co-expressing the mutant proinsulin with furin, a homologue of the
      yeast endoprotease, Kex2.

PMID- 1397293
TI  - Effect of thiamin on cordycepin sensitivity in Saccharomyces cerevisiae.
AB  - The sensitivity of Saccharomyces cerevisiae to the antibiotic cordycepin (3'
      deoxyadenosine) was found to be decreased by the addition of thiamin to the
      growth medium. A thiamin transport mutant of S. cerevisiae was also found to be
      resistant to the growth inhibitory effect of cordycepin. Not only the thiamin
      uptake but also adenosine uptake by this mutant cell was markedly reduced
      compared to those by the parent yeast cells. This strongly suggested that
      cordycepin, an analog of adenosine, is virtually taken up by the thiamin
      transport system of growing yeast cells; thus the drug sensitivity is decreased
      by the presence of thiamin in the growth medium.

PMID- 1397295
TI  - Muscarinic acetylcholine receptor produced in recombinant baculovirus infected
      Sf9 insect cells couples with endogenous G-proteins to activate ion channels.
AB  - Following the infection of insect ovarian cells (Sf9) with recombinant bearing
      the cDNA coding for the rat muscarinic acetylcholine (ACh) receptor subtype m3,
      ionic flux across the membrane in response to the application of ACh was examined
      electrophysiologically. We show that ACh activates potassium currents. The
      response is abolished when cells are treated with pertussis toxin. No ACh-induced
      currents are observed from uninfected cells or cells infected with virus which do
      not contain the cDNA coding for ACh receptors in its genome. The characteristics
      of single channel currents show time-dependent changes following the application
      of ACh. Initially, ACh activates brief channel currents with a conductance of
      about 5 pS. The conductance level of channels gradually increases in steps to 10
      pS and then to 20 pS and 40 pS. At the same time, channel open probability also
      increases. Thereafter, additional channels appear, opening and closing
      independently of, or at times in synchrony with, the original channel.

PMID- 1397294
TI  - Enhanced IgG- and complement-independent phagocytosis of sulfatide-enriched human
      erythrocytes by human monocytes.
AB  - Phagocytosis by adherent human monocytes of human erythrocytes (RBC), sulfatide
      enriched by incubation with 10(-12) to 10(-9) M cerebroside sulfate, was enhanced
      approx. 6-fold. Increased phagocytosis was observed only in RBC opsonized with
      fresh plasma, and not in non-opsonized or serum-opsonized RBC. Increased
      phagocytosis was immunoglobulin- and complement independent. Thrombospondin and
      von Willebrand factor, present in plasma but not in serum, and binding
      selectively to sulfatides, are likely mediators of the enhanced phagocytosis.

PMID- 1397296
TI  - Protein kinase C mutants in the auto-inhibitory region exhibit two distinct
      properties.
AB  - To define the role of the auto-inhibitory region of protein kinase C (PKC), Arg22
      Lys23-Gly24-Ala25-Leu26-Arg27, site-directed mutations were introduced into the
      basic residues. Three mutants, PKCAla22,23, PKCAla27, and PKCAla22,23,27,
      apparently fell into two distinct types with regard to their biochemical
      properties and biological activities, as judged by the enhancement of a c-fos
      promoter in Jurkat cells and by the initiation of germinal vesicle breakdown
      (GVBD) in Xenopus laevis oocytes. (i) PKCAla22,23 and PKCAla27 had activators
      independent in vitro kinase activity, high phosphorylation levels in vivo, and
      localized in both cytosolic and particulate fractions. These mutants were not
      fully biologically active. (ii) PKCAla22,23,27 had a low phosphorylation level in
      vivo, was found predominantly in the particulate fraction and was the most
      biologically active. These results suggest that basic residues in the auto
      inhibitory domain account for the regulation of kinase activity and the cytosolic
      retention of PKC. The particulate association or the cytosolic clearance of PKC
      may facilitate signal transduction in the cell.

PMID- 1397297
TI  - Binding of HIV-1 gp120 to the nicotinic receptor.
AB  - We previously described a significant sequence homology between HIV-1 gp120 and
      the functional sites responsible for the specific binding of snake curare-mimetic
      neurotoxins and rabies virus glycoprotein to the nicotinic acetylcholine
      receptor. Here we report findings about the existence of a mechanism of
      functional molecular mimicry which could enable the binding of HIV-1 gp120 to
      nicotinic acetylcholine receptors in muscle cells and neurons.

PMID- 1397299
TI  - Characterization of a multi-copy gene for a major stage-specific cysteine
      proteinase of Leishmania mexicana.
AB  - lmcpb, a gene from Leishmania mexicana that encodes a major cysteine proteinase
      in the parasite, has been cloned and sequenced. LmCPb is related more to cysteine
      proteinases from Trypanosoma brucei and Trypanosoma cruzi than to a previously
      characterized cysteine proteinase, LmCPa, of L. mexicana. It contains a long C
      terminal extension characteristic of similar enzymes of T. brucei and T. cruzi.
      The gene is multi-copy and tandemly arranged. lmcpb RNA levels are
      developmentally regulated with steady state levels being high in amastigotes, low
      in metacyclic promastigotes and undetectable in multiplicative promastigotes.
      This variation correlates with and may account for the stage-specific expression
      of LmCPb enzyme activity.

PMID- 1397298
TI  - Molecular cloning of a cDNA clone for tobacco lipid transfer protein and
      expression of the functional protein in Escherichia coli.
AB  - A cDNA clone encoding a lipid transfer protein (LTP) was isolated from tobacco by
      screening a library with a PCR-amplified spinach LTP gene. DNA sequence analysis
      showed a large open reading frame (344 bp) encoding a polypeptide of 114 amino
      acids. The first 23 amino acids of the deduced protein have the characteristics
      of a signal peptide for protein secretion or targeting into dense microbody-like
      vesicles. The cDNA clone was then inserted into an expression vector, pMAL, and
      expressed in E. coli as a fusion with the maltose binding protein (MBP). The MBP
      LTP fusion protein was purified to homogeneity and subjected to factor Xa
      cleavage to yield the LTP domain. A lipid transfer assay demonstrated that the
      resulting LTP was functional. The availability of the expression system in E.
      coli will facilitate the elucidation of in vivo function(s) of plant LTPs.

PMID- 1397300
TI  - The light-harvesting core-complex and the B820-subunit from Rhodopseudomonas
      marina. Part I. Purification and characterisation.
AB  - The BChla-containing B880-complex (core-complex) of Rhodopseudomonas marina
      (Rhodospirillaceae) was isolated with a new purification method. The isolation of
      the B880-complex was performed by solubilisation of the photosynthetic membranes
      with the detergent LDAO and subsequent fractionated ammonium-sulfate
      precipitation with about 50% recovery. The B880-complex retained its original
      spectral properties as revealed with absorption, fluorescence and circular
      dichroism spectroscopy. Furthermore, we dissociated the B880-complex with the
      detergent n-octyl-beta-glucoside (OG) and purified the developed subcomplex by
      the method of Miller et al. [1], which showed an absorption maximum at 820 nm
      (B820). The alpha- to beta-polypeptide ratio and the alpha- or beta-polypeptide
      to BChla ratio, respectively, were estimated to be 1:1 in both complexes. The
      molecular weights of the B880 and the B820-complexes, determined by gel
      filtration chromatography, were 181 and 32 kDa, respectively. Thus, it appears
      that the B880-complex of Rp. marina consists of 24 polypeptides and the B820
      complex of four polypeptides. Six B820-complexes or possible subunits could form
      the B880-complex. On the basis of these data we propose a model for the structure
      of BChla containing core-complexes.

PMID- 1397301
TI  - The light-harvesting core-complex and the B820-subunit from Rhodopseudomonas
      marina. Part II. Electron microscopic characterisation.
AB  - Electron micrographs of photosynthetic membranes of the BChla-containing
      bacterium Rp. marina showed a quasi-crystalline structure. The photoreceptor
      units are arranged in a hexagonal lattice with a reaction center to reaction
      center distance of 102 +/- 3 A. Purified B880-complex was concentrated up to an
      OD880 of 60 which induced the formation of large protein vesicles. The protein
      complexes within these vesicles were highly ordered and showed a hexagonal
      lattice with the same center to center distance of 102 +/- 3 A as was observed in
      the native membranes. Image processing of the micrographs revealed a ring-like
      structure of the B880-complex at 26 A resolution and suggests that the B880
      complex consists of 5 or 6 subunits. For the first time it can be shown that an
      isolated core-complex is in a stable, ring-like structure even without the
      reaction center which is supposed to be located in the middle of the B880-ring.
      The data indicate that the isolated B880-complex exhibits the same structure as
      in the native membrane.

PMID- 1397302
TI  - Identification by 1H NMR spectroscopy of flexible C-terminal extensions in bovine
      lens alpha-crystallin.
AB  - Two-dimensional 1H NMR spectroscopy of bovine eye lens alpha-crystallin and its
      isolated alpha A and alpha B subunits reveals that these aggregates have short
      and very flexible C-terminal extensions of eight (alpha A) and ten (alpha B)
      amino acids which adopt little preferred conformation in solution. Total alpha
      crystallin forms a tighter aggregate than the isolated alpha A and alpha B
      subunit aggregates. Our results are consistent with a micelle model for alpha
      crystallin quaternary structure. The presence of terminal extensions is a general
      feature of those crystallins, alpha and beta, which form aggregates.

PMID- 1397303
TI  - A cell free system reveals that capacitation is a prerequisite for membrane
      fusion during the acrosome reaction.
AB  - Plasma and outer acrosomal membranes were extracted from bovine spermatozoa and
      used in an in vitro fusion assay. Fusion was revealed by monitoring the merging
      of lipids using the chlorophyll a-N,N'-dioctadecyloxacarbocyanine-p-toluene
      sulfonate (DCY) method [(1984) Biochim. Biophys. Acta 769, 531-542]. The
      requirement for capacitation, as well as the effects of pH, calcium and spermine,
      on membrane fusion in our cell-free system were similar to those observed in vivo
      on the acrosomal reaction. This demonstrates for the first time that capacitation
      and alterations in intracellular pH and calcium concentration, which must precede
      the acrosomal reaction, are required for the membrane fusion event.

PMID- 1397304
TI  - Ascorbic acid oxidation: a potential cause of the elevated severity of
      atherosclerosis in diabetes mellitus?
AB  - The exposure of mouse peritoneal macrophages to cholesterol linoleate-containing
      artificial lipoproteins can lead to intracellular ceroid accumulation. This can
      be used as a model to study the role of oxidation in macrophage uptake of
      lipoproteins containing unsaturated fatty acids, considered by many as a primary
      event in atherosclerotic plaque formation. Our studies show that ascorbic acid
      can both inhibit and promote the formation of ceroid in such a model system. The
      transition metal copper (Cu(II)) further elevates ceroid accumulation and EDTA, a
      metal chelator, inhibits it. When trace levels of transition metals are present,
      low concentrations of ascorbic acid can elevate ceroid formation. This pro- and
      antioxidant characteristic of ascorbic acid was confirmed by monitoring the
      generation of oxidants by various concentrations of ascorbic acid, assessed by
      benzoic acid hydroxylation or the fragmentation of BSA. We discuss these
      observations in the context of an apparent increase in ascorbic acid oxidation
      and elevated severity of atherosclerosis in diabetes mellitus.

PMID- 1397305
TI  - Selective dehydrogenation (oxidation) of 3,4-dimethoxybenzyl alcohol by a non
      heme iron lignin-peroxidase reaction mimic.
AB  - In pyridine, bis(2,2'-bipyridine)iron(II) (Fe(bpy)2+(2)) activates hydrogen
      peroxide for the efficient and selective catalytic dehydrogenation (oxidation) of
      veratryl alcohol (model-substrate monomer for lignin; 3,4-(MeO)2PhCH2OH). Several
      other complexes (FeII(OPPh3)2+(4), FeII(O2bpy)2+(2), FeII(MeCN)2+(4), FeII(PA)2,
      FeIIICl3) are effective catalysts for the dehydrogenation of veratryl alcohol and
      benzyl alcohol, but their selectivity (relative reactivity with 3,4-(MeO)2PhCH2OH
      vs. PhCH2OH) is less than the 6.1 ratio that is observed for the optimized
      FeII(bpy)2+(2)/H2O2/pyridine (py) system. The reactivities have been determined
      for several other methoxybenzyl alcohols that are model substrates for lignin
      (e.g., 4-MeOPhCH2OH and (MeO)3PhCH2OH).

PMID- 1397306
TI  - The PSI-E subunit of photosystem I binds ferredoxin:NADP+ oxidoreductase.
AB  - A photosystem I complex containing the polypeptides PSI-A to PSI-L, light
      harvesting complex I and ferredoxin:NADP+ oxidoreductase has been isolated from
      barley using the non-ionic detergent n-decyl-beta-D-maltopyranoside. The ratio
      between bound ferredoxin:NADP+ oxidoreductase and P700 is 0.4 +/- 0.2. The
      complex is highly active in catalyzing light-induced transfer of electrons from
      plastocyanin to NADP+ at rates of 280 +/- 150 and 1800 +/- 800 mumol NADPH/(mg
      chl.h), without and in the presence of saturating amounts of exogenously added
      ferredoxin:NADP+ oxidoreductase, respectively. Endogenously bound
      ferredoxin:NADP+ oxidoreductase interacts with the PSI-E subunit as demonstrated
      by cross-linking experiments using two different types of cross-linkers and
      identification of the products by Western blotting and the use of monospecific
      antibodies.

PMID- 1397307
TI  - Identification of a domain of ETA receptor required for ligand binding.
AB  - Various chimeric ETA and ETB receptors were produced in CHO cells for the
      elucidation of a specific domain which influences the affinity of the receptor
      toward BQ-123, a selective ETA antagonist. Replacement of the first extracellular
      loop domain (B-loop) of the ETA receptor with the corresponding domain of the ETB
      receptor, reduced the inhibition by BQ-123 drastically, while the replacements of
      other extracellular domains of ETA did not. By contrast, the introduction of the
      B-loop of ETA in place of the corresponding domain of the ETB receptor endowed
      the ETB-based chimeric receptor with a sensitivity to BQ-123. These observations
      suggest that the B-loop domain of the ETA receptor is involved in ligand binding.

PMID- 1397308
TI  - A comment on: 'effect of starvation on glucose transport and membrane fluidity in
      rat intestinal epithelial cells', by: P.D. Gupta and A.A. Wahead (FEBS Letters,
      300: 263-267).

PMID- 1397309
TI  - Ligand-activated ion channels may share common gating mechanisms with the Shaker
      potassium channel.
AB  - This paper proposes a detailed gating mechanism for the N-methyl-D-aspartate
      (NMDA) channel. In the NMDAR1 subunit, the signal of agonist binding may be
      carried from Y456 to W590 through an electron transport chain, including W480
      which could be the glycine modulatory site. The channel's opening may arise from
      repulsion between negatively charged W590s, analogous to W435s of the Shaker K+
      channel. The cyclic nucleotide-gated channels may be activated by a similar
      mechanism, but the opening of nicotinic acetylcholine receptor (nAChR) channels
      is likely to be initiated by the formation of tyrosine radicals. The role of
      disulfide-bonded cysteines in the redox modulation can also be explained.

PMID- 1397310
TI  - Localization of myosin IIB at the leading edge of growth cones from rat dorsal
      root ganglionic cells.
AB  - Primary cultures of rat dorsal root ganglionic (DRG) cells were stained with
      isoform-specific antibodies against non-muscle myosin II. Antibodies against the
      brain type myosin (MIIB) stained the peripheries of growth cones and non-neuronal
      cells. Double staining of the cells with the anti-myosin antibodies and rhodamine
      phalloidin or anti-actin antibodies indicated that MIIB co-exists, with F-actin,
      at the leading edge. Antibodies against platelet myosin stained neither leading
      edges nor neurites, but stained the cell bodies of neurons and the stress fibers
      of non-neuronal cells. These results suggest that MIIB functions in the motility
      of the leading edge of DRG cells.

PMID- 1397311
TI  - Pulsed electric current enhances the phorbol ester induced oxidative burst in
      human neutrophils.
AB  - Oxidative burst (OB) response in human neutrophils, measured with
      chemiluminescence (CL), has been used to determine whether pulsed electric
      current (PEC) might induce a functional response in these electrically
      nonexcitable cells, and also whether it might modify cellular response to tumor
      promoting phorbol ester (PMA). Five minutes of PEC treatment caused no
      significant changes in neutrophil CL levels in HBSS (1.2 mM Ca2+ concentration)
      as well as in HBSS-EGTA, where the extracellular Ca2+ concentration was reduced
      to less than 30 nM. The CL level of PMA-activated neutrophils in HBSS was 52%
      higher than in HBSS-EGTA. In HBSS the CL level, after the combined PMA and PEC
      treatment, was 53% higher than in PMA-alone-treated neutrophils. Activation of
      the OB in HBSS-EGTA with PMA and PEC was 13% higher than in solely PMA treated
      neutrophils. The results suggest that in neutrophil OB response, the PEC effect
      is closely related with cellular calcium mobilization, since depletion of
      extracellular Ca2+ decreased the PEC effect.

PMID- 1397312
TI  - Plasma membrane redox activity correlates with N-myc expression in neuroblastoma
      cells.
AB  - In different neuroblastoma cell lines and transfected clones, an increasing
      plasma membrane redox activity correlates with amplification and enhanced
      expression of the N-myc oncogene. Furthermore, plasma membrane redox activity is
      partially inhibited by retinoic acid in neuroblastoma cells with multiple copies
      of the N-myc oncogene but not in neuroblastoma cells with only one copy of this
      gene.

PMID- 1397313
TI  - Magnesium deficiency in vitro enhances free radical-induced intracellular
      oxidation and cytotoxicity in endothelial cells.
AB  - The effect of magnesium (Mg)-deficient culture on endothelial cell susceptibility
      to oxidative stress was examined. Bovine endothelial cells were cultured in
      either control sufficient (0.8 mM) or deficient (0.4 mM) levels of MgCl2. Oxygen
      radicals were produced extracellularly by the addition of dihydroxyfumarate and
      Fe(3+)-ADP. Isolated Mg-deficient endothelial cells produced 2- to 3-fold higher
      levels of thiobarbituric acid (TBA)-reactive materials when incubated with this
      free radical system. Additional studies were performed using digitized video
      microscopy and 2',7'-dichlorofluorescein diacetate (DCFDA) as an intracellular
      indicator for oxidative events at the single cell level. In response to the
      exogenous oxidative stress, endothelial cells exhibited a time-dependent increase
      in fluorescence, suggestive of intracellular lipid peroxidation. The increase in
      cellular fluorescence began within 1 min of free radical addition; the Mg
      deficient cells exhibited a more rapid increase in fluorescence than that of Mg
      sufficient cells. In separate experiments, cellular viability was assessed using
      the Trypan blue exclusion assay. Mg deficiency increased cytotoxicity of the
      added oxyradicals, but the loss of cellular viability began to occur only after
      15 min of free radical exposure, lagging behind the detection of intracellular
      oxidation products. These results suggest that increased oxidative endothelial
      cell injury may contribute to vascular injury during Mg deficiency.

PMID- 1397314
TI  - Phenylalanyl-tRNA synthetase from Thermus thermophilus can attach two molecules
      of phenylalanine to tRNA(Phe).
AB  - Phenylalanyl-tRNA synthetase from the extreme thermophilic bacterium Thermus
      thermophilus can incorporate more than one molecule of phenylalanine into the
      tRNA(Phe). It is shown that the 'hyperaminoacylated' tRNA(Phe) is the bis-2',3'-O
      phenylalanyl-tRNA(Phe), and its formation is typical for the thermophilic enzyme
      but does not occur for E. coli phenylalanyl-tRNA synthetase under the same
      conditions.

PMID- 1397315
TI  - Ribosomal localization of the mRNA in the 30S initiation complex as revealed by
      UV crosslinking.
AB  - Translation initiation complexes consisting of 30S ribosomal subunits, 32P
      labelled mRNA (002 mRNA), fMet-tRNA and the three initiation factors were
      subjected to UV-crosslinking to determine the protein and rRNA neighbors of the
      bound mRNA by immunochemical methods and by nucleic acid hybridization
      techniques. The mRNA was found to be crosslinked to a specific region of the 16S
      rRNA spanning from nucleotide 418 to 615 and to ribosomal proteins S1 and S21
      (the main targets), S3, S10, S12 and S14; a low level of crosslinking was also
      detected with S2, S7, S13, S18 and S19.

PMID- 1397316
TI  - p33, an endogenous target protein for arginine-specific ADP-ribosyltransferase in
      chicken polymorphonuclear leukocytes, is highly homologous to mim-1 protein (myb
      induced myeloid protein-1).
AB  - We have determined the partial amino acid sequence of p33, an endogenous
      substrate protein for arginine-specific ADP-ribosyltransferase in chicken
      polymorphonuclear leukocytes (heterophils), and found that the sequence was
      completely identical with the regions of amino acid sequences deduced from mim-1
      (named for myb-induced myeloid protein-1, which is expressed in chicken
      promyelocytes) cDNA [(1989) Cell, 59, 1115-1125], except for one amino acid
      difference (Tyr297-->Ile). These results together with data on cellular and
      subcellular distributions of p33 in heterophils suggest that mim-1 may encode the
      precursor protein of p33.

PMID- 1397317
TI  - Glycine and beta-branched residues support and modulate peptide helicity in
      membrane environments.
AB  - Transmembrane (TM) segments of integral membrane proteins are putatively alpha
      helical in conformation once inserted into the membrane, yet consist of primary
      sequences rich in residues known in soluble proteins as helix-breakers (Gly) and
      beta-sheet promoters (Ile, Val, Thr). To examine the specific 2 degrees structure
      propensities of such residues in membrane environments, we have designed and
      synthesized a series of 20-residue peptides with 'guest' hydrophobic segments-
      expected to provide three turns of incipient alpha-helix content--embedded in
      'host' hydrophilic (Lys-Ser) matrices. Circular dichroism (CD) spectra of the
      model peptides in water showed that significant helical content was observed only
      for peptides with high Ala content; others behaved as 'random coils'. However, in
      the membrane-mimetic environment of sodium dodecylsulfate (SDS) micelles, it was
      found that Gly can be accommodated as readily as Ala, and Ile or Val as readily
      as Leu, in hydrophobic alpha-helices. Further subtleties of structural
      preferences could be observed in electrically-neutral lyso-phosphatidylcholine
      (LPC) micelles, where helical propensity decreased in the order Ala-Leu-rich >
      Gly-Leu-rich > Gly-Ile(Val)-rich hydrophobic segments. The results conjure a role
      of environment-dependent helix-modulation for Gly, Ile, and Val residues--and
      suggest that these residues may provide, in part, the structural basis for
      conformational transitions within or adjacent to membrane domains, such as those
      accompanying membrane insertion and/or required for transport or signalling
      functions.

PMID- 1397318
TI  - A long-lived state for influenza virus-erythrocyte complexes committed to fusion
      at neutral pH.
AB  - The low pH-induced fusion of influenza virus with intact erythrocyte plasma
      membranes is preceded by a delay time following pH reduction, that is itself pH-
      and temperature dependent. At 37 degrees C/pH 4.8, lipid mixing between virus and
      target membranes begins < 2 s after pH reduction, whereas at 4 degrees C/pH 4.8,
      fusion does not commence until > 10 min after pH reduction. We have found that
      within this time period at 4 degrees C, a population of virus acquires the
      capacity to subsequently undergo fusion with high efficiency at elevated
      temperatures and pH 7.4. Both the kinetics and the extent of this pH 7.4 fusion
      depend upon the time of pre-incubation at pH 4.8/4 degrees C. Incubation at pH
      7.4/4 degrees C, following this pre-incubation does not result in fusion, but the
      capacity to fuse at pH 7.4/37 degrees C is retained for a time period exceeding 1
      h. The longevity of this fusion committed state makes it amenable to biochemical
      and immunological analysis. We have shown that it is insensitive to
      dithiothreitol, neuraminidase and trypsin, but is incapacitated by thermolysin or
      protease K. We conclude that only the HA2 sub-unit of influenza haemagglutinin is
      a necessary protein component of later stages of the fusion pathway.

PMID- 1397319
TI  - Conformation and length of the signal sequence affect processing of secretory
      protein.
AB  - Processing of human lysozyme with artificially designed signal sequences was
      examined in an in vitro translation-translocation system and compared with their
      secretory capabilities in yeast. It has been shown that the conformation of the C
      terminal region of the signal sequence and the length of the hydrophobic segment
      are important factors for efficient cleavage of the signal sequence.

PMID- 1397320
TI  - Malarial toxic antigens synergistically enhance insulin signalling.
AB  - Hypoglycaemia is a major complication of severe malaria [(1990) Trans. Roy. Soc.
      Trop. Med. 84 (suppl. 2) 1-65], especially cerebral malaria, in which it is
      associated with increased mortality [(1990) Lancet 336, 1039-1043; (1989) Quart.
      J. Med. (New series) 71, 441-459]; however, the mechanisms responsible have not
      been fully explained. Preparations containing toxic malaria antigens (TMA)
      released by blood stage Plasmodium yoelii malaria parasites have been shown to
      induce hypoglycaemia in mice lasting at least 8 h [(1992) Clin. Exp. Immunol. (in
      press)]. Here we report that TMAs can act synergistically with insulin in both
      stimulating lipogenesis and inhibiting lipolysis in rat adipocytes in vitro, and,
      furthermore, that they act synergistically with insulin in the induction of
      hypoglycaemia in vivo.

PMID- 1397321
TI  - Chemically synthesized 182-235 segment of tau protein and analogue peptides are
      efficient in vitro microtubule assembly inducers of low apparent sequence
      specificity.
AB  - A 54-amino acid peptide reproducing the first and second repeats and intervening
      spacer sequence of the tubulin binding motif (residues 182-235) of murine tau
      protein, and several congeners representing different degrees of sequence
      scrambling have been prepared by solid phase methods and fully characterized
      chemically. These double-repeat peptides have been shown to induce microtubule
      formation at concentrations about one order of magnitude lower than single-repeat
      controls, under conditions close to the critical concentration needed for tubulin
      self-assembly. On the other hand, partial loss of microtubule-inducing capacity
      was observed for peptides with primary structures increasingly disorganized with
      respect to the canonical peptide. These results call into question the assumption
      that a high degree of primary structure specificity is involved in the tau
      tubulin interaction leading to in vitro microtubule formation.

PMID- 1397322
TI  - Hepatocyte swelling leads to rapid decrease of the G-/total actin ratio and
      increases actin mRNA levels.
AB  - Exposure of isolated rat hepatocytes to hypotonic (190 mosmol/l) incubation media
      lowered the cellular G-actin level without affecting the total actin content:
      here the G-/total actin ratio decreased by 15.5 +/- 1.4% (n = 7). Similar effects
      were observed following isotonic cell swelling by either addition of glutamine
      (10 mM) or insulin (100 nM), resulting in a decrease of the G-/total actin ratios
      by 13.5 +/- 2.1% (n = 5) and 14.1 +/- 1.1% (n = 11), respectively. The effects of
      hypotonic exposure, glutamine and insulin on the G-/total actin ratio largely
      occurred within 1 min and persisted for at least 2 h in presence of the
      respective effectors. After a 120 min exposure to hypotonic media, glutamine or
      insulin the actin mRNA levels were increased 2.4-, 2.0- and 3.6-fold,
      respectively. Hypertonic exposure lowered the G-/total actin ratio by only 4.9 +/
      2.5% (n = 4) and increased actin mRNA levels only 1.2-fold. There was a close
      relationship between glutamine- and hypotonicity-induced cell swelling and the
      decrease of G-/total actin ratios. The data suggest that cell swelling exerts
      rapid and marked effects on the state of actin polymerization and increases actin
      mRNA levels. Thus, cytoskeletal alterations in response to cell swelling may be
      involved in the regulation of hepatic metabolism by cell volume.

PMID- 1397323
TI  - Modulation of the glucagon-dependent activation of the phosphoenolpyruvate
      carboxykinase gene by oxygen in rat hepatocyte cultures. Evidence for a heme
      protein as oxygen sensor.
AB  - The glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK)
      gene is modulated by oxygen. It was proposed that heme proteins might function as
      O2 sensors; their actions are impaired after replacement of the central Fe2+ ion
      by Co2+ and inhibition of heme synthesis by succinylacetone (SA). Therefore, the
      effects of CoCl2 and SA, alone and in combination, on the glucagon-dependent
      induction of PCK activity and PCK mRNA were investigated at different
      physiological oxygen tensions in primary rat hepatocyte cultures. The cells were
      exposed to 50 microM CoCl2 and/or 2 mM SA from 4-24 h. After addition of fresh
      media without CoCl2 or SA, PCK was induced with 1 nM glucagon. PCK activity and
      PCK mRNA were elevated to 100% at 16% O2 and to about 65% at 8% O2. CoCl2 reduced
      these increases to about 45% at 16% O2 and to about 35% at 8% O2. SA lowered the
      inductions to about 50% and 40% each at 16% and 8% O2. CoCl2 plus SA diminished
      the elevations to about 5% at both oxygen tensions. In the presence of CoCl2
      and/or SA, ornithine decarboxylase induction by insulin was not impaired; lactate
      dehydrogenase did not leak from the cells, which in electron microscopical
      inspections had normal cell structures. These findings support the hypothesis
      that a heme protein is involved in the activation of the PCK gene and that it
      acts as an O2 sensor.

PMID- 1397325
TI  - Nucleocapsid protein of HIV-1 and its Zn2+ complex formation analysis with
      electrospray mass spectrometry.
AB  - The Zn2+ binding properties of the synthetic nucleocapsid protein (Ncp7) of HIV
      1, containing two zinc-binding domains, have been studied using electrospray mass
      spectrometry (ES-MS). ES-MS measurements revealed strong binding of Zn2+ by Ncp7.
      Its shorter fragments, Ncp7-(1-35)- and (29-55)-peptides, each containing only
      one zinc-binding domain, bind one equivalent of Zn2+ ions tightly. ES-MS studies
      allows these fragments to be distinguished in terms of their binding affinity:
      they showed stronger binding of Zn2+ by Ncp7-(1-35)-peptide. Surprisingly, in
      addition to the expected two zinc-binding domains, a third metal binding site was
      detected in Ncp7. However, this site appears to bind different metal ions without
      selectivity and most probably reflects salt formation at the C-terminal acidic
      residues.

PMID- 1397324
TI  - The secondary structure of influenza A M2 transmembrane domain. A circular
      dichroism study.
AB  - Using circular dichroism, this study investigated the secondary structure of the
      influenza A M2 transmembrane domain. When reconstituted into 1,2-dioleoyl-sn
      glycero-3-phosphocholine liposomes, the M2 transmembrane domain was found to
      adopt a predominantly alpha-helical secondary structure which was unaffected by
      both temperature and the addition of 1-aminoadamantane hydrochloride.
      Reconstitution into 1,2-dioleoyl-sn-glycero-3-phosphoglycerol liposomes resulted
      in a marked decrease in helical content.

PMID- 1397326
TI  - Effects of 1,3-chelation induced by cis-diamminedichloroplatinum(II) on the
      stability of DNA duplexes.
AB  - Several 1,3-intra-strand cross-linked decadeoxynucleotide duplexes, modified with
      cis-diamminedichloroplatinum(II) (cis-DDP), and their base substitution analogues
      at the complementary site to the intervening base of the coordination sites, were
      synthesized and measured for UV-melting profiles to determine melting temperature
      (Tm) values. The results indicated the thermal stability of the oligonucleotide
      duplexes containing Pt-induced 1,3-intra-strand cross-linking did not depend on
      the kind of intervening base of the coordination site but rather on its
      complementary base. These results may explain the mutagenicity of cis-DDP from a
      chemical aspect.

PMID- 1397327
TI  - Kinetics of the N intermediate and the two pathways of recovery of the ground
      state of bacteriorhodopsin.
AB  - Absorption kinetic measurements at alkaline pH, in which bacteriorhodopsin (BR)
      is pre-excited by another flash, indicate that a part of the recovery of the BR
      ground-state is faster than the decay of the N intermediate of the photocycle.
      This fact proves the existence of a parallel pathway in the late part of the BR
      photocycle (the decay of Ms into BR), which does not include the N intermediate.
      We demonstrate that the decay of the Mf intermediate does not lead to any direct
      recovery of the BR ground-state, and that excitation of N does not form an M-like
      intermediate. Mf decays directly into the N intermediate, and photoexcitation of
      N leads to the formation of a red-shifted form, O*. The kinetics of this red
      shifted intermediate are also presented.

PMID- 1397328
TI  - Sequence analysis of pigeon delta-crystallin gene and its deduced primary
      structure. Comparison of avian delta-crystallins with and without endogenous
      argininosuccinate lyase activity.
AB  - delta-Crystallin is a major lens protein present in the avian and reptilian
      lenses. To facilitate the cloning of the delta-crystallin gene, cDNA was
      constructed from the poly(A)+ RNA of pigeon lenses, amplified by the polymerase
      chain reaction (PCR). The PCR product was then subcloned into pUC19 vector and
      transformed into E. coli strain JM109. Plasmids purified from the positive clones
      were prepared for nucleotide sequencing by the dideoxynucleotide chain
      termination method. Sequencing two clones, containing 1.4 kb DNA inserts coding
      for delta-crystallin allowed the construction of a complete, full-length reading
      frame of 1,417 bp covering a deduced protein sequence of 466 amino acids,
      including the universal translation-initiating methionine. The pigeon delta
      crystallin shows 88, 83 and 69% sequence identity to duck delta 2, chicken delta
      1 crystallins and human argininosuccinate lyase respectively. It is also shown
      that, in contrast to duck delta 2 crystallin which has a high argininosuccinate
      lyase activity, pigeon delta-crystallin appears to contain very low activity of
      this enzyme, despite the fact that they share a highly homologous structure. A
      structural comparison of delta-crystallins with or without enzymatic activity
      suggested several amino acid replacements which may account for the loss of
      argininosuccinate lyase activity in the lenses of certain avian species.

PMID- 1397329
TI  - Structural relationship between lipases and peptidases of the prolyl
      oligopeptidase family.
AB  - In prolyl oligopeptidase and its homologues, which constitute a new serine
      protease family, the order of the catalytic Ser and His residues in the amino
      acid sequence is the reverse of what is found in the trypsin and subtilisin
      families. The exact position of the third member of the catalytic triad, an Asp
      residue, has not yet been identified in the new family. Recent determination of
      the three-dimensional structures of pancreatic and microbial lipases has shown
      that the order of their catalytic residues is Ser, Asp, His, and this fits the
      order Ser, His of prolyl oligopeptidase. However, there is no sequence homology
      between lipases and peptidases, except for a 10-residue segment, which
      encompasses the essential Ser, and for the immediate vicinity of the catalytic
      Asp and His residues. This comparison identifies the catalytic Asp residue in the
      prolyl oligopeptidase family. The relative positions of the three catalytic
      residues in peptidases and microbial lipases were the same and this indicated
      structural and possibly evolutionary relationship between the two families.

PMID- 1397330
TI  - Cloning and expression of a novel mouse somatostatin receptor (SSTR2B).
AB  - A mouse somatostatin (SS) receptor cDNA was cloned from neuroblastoma x glioma
      (NG108-15) cells. The sequence is almost identical to that of the mouse SSTR2
      receptor [(1992) Proc. Natl. Acad. Sci. USA 89, 251)] but lacks about 300
      nucleotides between transmembrane domain VII and the C-terminus. This spliced
      variant of SSTR2 (designated SSTR2B) encodes a protein which is 23 residues
      shorter than that predicted from the SSTR2 sequence, and differs in 15 amino
      acids at the C-terminus. mRNA corresponding to SSTR2B occurs in mouse tissues in
      higher abundance than that of SSTR2. SSTR2B binds SS peptides with high affinity
      when expressed in mammalian cells.

PMID- 1397331
TI  - Regulation of arachidonate-mobilizing phospholipase A2 by phosphorylation via
      protein kinase C in macrophages.
AB  - Stimulation of 32P-labeled macrophages with phorbol ester caused an increase in
      phosphorylation of the intracellular, high molecular weight phospholipase A2.
      This increase in phosphorylation was accompanied by an increase in enzyme
      activity, but led to no detectable shift in the concentration dependence for
      Ca(2+)-induced activation. The phosphorylated phospholipase A2 could be
      dephosphorylated by treatment with acid phosphatase, and such treatment also
      reduced its catalytic activity. Together with previous data, these results
      indicate that the arachidonate-mobilizing phospholipase A2 is dually regulated by
      Ca2+ (membrane interaction) and by phosphorylation (catalytic activity).

PMID- 1397332
TI  - No evidence for calpain I involvement in fodrin rearrangements linked to
      regulated secretion.
AB  - Stimulation of secretion in chromaffin and parotid acinar cells is associated
      with dramatic rearrangements of the subplasmalemmal cytoskeleton, notably of
      fodrin and F-actin. It has been proposed that a proteolytic cleavage of fodrin
      resulting from an activation of the neutral calcium activated protease (calpain)
      could be responsible for these changes. Using an affinity-purified anti-alpha
      fodrin antibody, several cleavage products of fodrin could clearly be detected
      following incubation of total cell homogenates from chromaffin and parotid acinar
      cells with purified calpain I. On the other hand, maximum stimulation of
      secretion of chromaffin cells by nicotine, and of parotid acinar cells by
      carbachol plus isoproterenol, was not associated with an increased appearance of
      cleavage products of fodrin. This result is not compatible with the 'proteolytic
      cleavage' hypothesis.

PMID- 1397333
TI  - Genomic organization and full-length cDNA sequence of human collagen X.
AB  - We have determined the full-length cDNA sequence of the human alpha 1(X) collagen
      gene by sequence analysis of a genomic clone ERG [(1991) Dev. Biol. 148, 562
      572], and of cDNA fragments generated from a reverse transcribed as alpha 1(X)
      mRNA by PCR. We defined the promoter region, the transcription initiation site
      and the full-length 5'-untranslated region. We also report the exon/intron
      boundaries of the transcript and the complete 3'-untranslated region as well as a
      3'-flanking sequence containing two additional polyadenylation signals. The
      promoter region is homologous to chicken and mouse type X promoters within
      several highly conserved regions. The genomic organization shows high homologies
      to chicken and mouse.

PMID- 1397334
TI  - Deletion of internal twenty-one amino acid residues of Escherichia coli
      prolipoprotein does not affect the formation of the murein-bound lipoprotein.
AB  - Mutation pgsA affecting the phosphatidylglycerol phosphate synthesis is lethal
      for all but certain E. coli strains such as strains deleted for the lpp gene or
      strains containing unmodifiable prolipoprotein like lppD14. Strain SD312 pgsA3 is
      tolerant to pgsA mutation, which suggests the lpp alleles in strain SD312 pgsA3
      and its parental strain SD12 may be defective. DNA sequence analysis of the lpp
      genes in Escherichia coli strains SD12 and SD312 pgsA using asymmetric polymerase
      chain reaction showed that the lpp alleles in these two strains contained a 63
      base pair deletion corresponding to the 37th to 57th codons of the wild-type lpp
      gene. [3H]Palmitate labeling of strains SD12 and SDS312 showed that the mutant
      lipoprotein in SD12 strain was modified with lipid, while the prolipoprotein in
      SD312 was not modified. The shortened mature lipoprotein in SD12 and the lipid
      modified prolipoprotein in globomycin-treated SD12 were found to be covalently
      attached to the peptidoglycan, while the unmodified prolipoprotein in SD312 did
      not form significant amounts of murein-bound lipoprotein.

PMID- 1397335
TI  - Pulmonary embolism in surgical practice.

PMID- 1397337
TI  - Unresolved pulmonary embolism: the value of surgical management with extensive
      thrombo-endarterectomy.
AB  - In a small but definite number of patients with pulmonary embolism, either
      gradual resolution of the embolus does not occur or recurrent showers of emboli
      follow the acute onset, leading to a state of chronic pulmonary hypertension. Two
      new cases treated surgically without the use of cardiopulmonary bypass are
      described. The results were excellent in both cases with relief of the dyspnoea
      and an improvement in the PO2, a result that has been documented in the follow-up
      of 2-6 years. The only definite treatment of this chronic obstructive pulmonary
      hypertension is pulmonary thrombo-endarterectomy.

PMID- 1397336
TI  - Surveillance of lower extremity vein grafts.
AB  - Development of stenosis in lower extremity vein grafts or its anastomotic
      segments is responsible for most graft failures. While these lesions can be
      treated by minor procedures, timely identification may improve long-term graft
      patency. In this review, diagnostic methods that are currently applied for vein
      graft surveillance, criteria for stenosis and recommendations for intervention
      are discussed.

PMID- 1397338
TI  - Non-invasive monitoring of cardiac output changes during aortic cross-clamping
      for infrarenal reconstruction--a new technique using suprasternal Doppler-derived
      cardiac output.
AB  - There is a significant morbidity and mortality associated with elective
      infrarenal aortic reconstruction. To examine the value of continuous cardiac
      output monitoring for predicting those at risk, 40 consecutive patients were
      monitored using Doppler-derived cardiac output. The anaesthetist was blind to all
      information from the monitor and managed the patients using standard techniques.
      In 28 patients there were no observed changes, while in seven, cardiac output
      rose after aortic cross-clamping. In five patients a fall in cardiac output
      occurred after cross-clamping. No cardiac events or cardiac deaths occurred in
      the 35 patients who showed a rise or no change in cardiac output. However, there
      were three cardiac events, including one cardiac death in the group of five
      patients in whom a fall in cardiac output was observed. It would appear that
      intraoperative non-invasive Doppler-derived cardiac output monitoring
      successfully predicts high-risk patients who would perhaps benefit from more
      intensive pre-, peri- and postoperative care.

PMID- 1397339
TI  - Fibro-muscular renal artery disease treated by extracorporeal vascular
      reconstruction and renal autotransplantation: short- and long-term results.
AB  - Over a 16-year period (1973-1989), 63 renal autotransplants were performed in 59
      patients for fibro-muscular dysplasia (FMD) with renal artery stenoses (42
      kidneys) or aneurysms (21 kidneys). About two-thirds of the autotransplants were
      performed before percutaneous transluminal angioplasty (PTA) was established for
      clinical use. However, vascular disease at a site or type not suitable for PTA
      was present in 57 (90%) of the kidneys. Hypertension was the leading symptom in
      56 patients, including four in whom renal autotransplantation was performed as an
      emergency for acute renal artery occlusion or malignant hypertension. Blood
      pressure returned to normal or improved in 51 (91%) and remained unchanged in
      five patients (9%) following autotransplantation. Three patients with renal
      artery aneurysm in whom haematuria and loin pain were the indications for
      treatment, became asymptomatic following surgical intervention. Bilateral renal
      autotransplantation was performed synchronously in one and sequentially in three
      patients. There were no operative deaths, but two kidneys were lost
      postoperatively in two 2-year-old children owing to renal vascular thrombosis. In
      the follow-up period (mean 4.3 years), one additional kidney was lost at 3 months
      owing to progressive FMD. Blood pressure and renal function remained stable in
      all other patients. Based on the excellent results achieved in this series, it is
      concluded that extracorporeal vascular repair and renal autotransplantation is a
      safe procedure for the patient as well as the kidney affected by FMD. The
      procedure is advocated as an alternative to in situ reconstruction in patients
      with renal artery disease not accessible to PTA, such as aneurysms and complex
      branch renal artery stenoses.

PMID- 1397340
TI  - Renal artery aneurysm: surgical indications and results.
AB  - The clinical course of 23 patients with 28 renal artery aneurysms (RAAs) is
      reported. The RAAs were recorded over a period of 10 years. Thirty-five per cent
      of the RAAs (eight of 23 patients) were detected during the investigation of
      hypertension, whereas 26% (six of 23 patients) were discovered incidentally while
      imaging atherosclerotic arterial disease in the aorto-iliac region by
      angiography. Twenty-two aneurysms were treated surgically and primary nephrectomy
      was necessary in one case. The surgical technique used was excision of the
      aneurysm with bypass grafting in 13 cases (seven Dacron, five vein, one arterial
      bypass), a running suture following aneurysm excision in four cases and an end-to
      end anastomosis in two cases. The results (for a period of 1-10 years) were
      excellent in all but three cases: two early graft occlusions (vein interposition)
      and one late occlusion (Dacron bypass) in the course of a re-operation which had
      become necessary because of a ruptured aneurysm of the gastro-epiploic artery
      after 3 months. Three of 23 patients were treated by embolisation of four
      intraparenchymal aneurysms. The follow-up of a non-treated saccular aneurysm
      showed a total thrombosis of the aneurysm within 4 years and fixed renal
      hypertension developed later in this patient. We suggest surgical repair of an
      RAA regardless of its size and the clinical symptoms, in order to prevent
      microembolism into the renal parenchyma and to avoid the development of fixed
      renal hypertension. Intrarenal aneurysms can be treated by embolisation to stop
      severe haematuria thus preserving the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397342
TI  - Wound infection after arterial surgical procedures.
AB  - During the period October 1983 to March 1987, 603 patients who underwent arterial
      surgical procedures were studied to determine the incidence and treatment of
      wound infections. Bypass procedures were performed in 395 patients (65.5%), in
      which autogenous vein was used for 158 grafts (26%), synthetic Dacron for 216
      grafts (36%), and umbilical vein for 21 grafts (3.5%). Thrombo-endarterectomies,
      embolectomies and patch-grafts were performed in 208 patients (34.5%). An
      Infection Control Nurse examined and registered the wounds. The definition of
      wound infection used in our study is equivalent to Szilagyi grade II infection.
      Vascular surgery is classified as clean surgery, the clean wound infection rate
      being a useful measurement to evaluate preventative measures and surgical
      technique. Thirty-one patients (5.1%) developed a wound infection as a
      postoperative complication. The overall incidence of wound complications
      including haematoma and seroma following arterial reconstruction was 13%. The
      site of wound infection was predominantly the groin. The most common pathogen was
      Staphylococcus aureus which was found in 17 patients (2.8%). All infections
      resolved without further surgical intervention. The influence of possible
      aetiological factors is considered and the importance of prophylactic antibiotics
      and good surgical technique is stressed.

PMID- 1397341
TI  - Endothelial cell seeding of damaged native vascular surfaces: prostacyclin
      production.
AB  - Endothelial cell seeding has been successful in reducing the thrombogenicity of
      prosthetic vascular grafts in animal and clinical studies. The reduction in
      thrombogenicity may be attributed to the intrinsic properties of endothelial
      cells themselves, and their ability to produce anti-thrombogenic mediators such
      as prostacyclin, and endothelium-derived relaxing factor. Endothelial seeding of
      damaged vascular surfaces produced during percutaneous transluminal angioplasty
      and endarterectomy is an attractive possibility due to the excellent attachment
      characteristics of the sub-endothelial tissue exposed during these procedures.
      The ability of endothelial seeded damaged vascular surfaces to produce
      prostacyclin was measured in an in vitro model of vascular injury. Endothelial
      seeded damaged surfaces produced significantly higher prostacyclin release than
      did vessels damaged by balloon dilatation (265.5 pg cm-2 min-1 and 87.5 pg cm-2
      min-1 respectively). This study provides evidence that endothelial seeding of
      damaged native vascular surfaces is technically feasible and that seeding may
      reduce the thrombogenicity of vascular surfaces following balloon dilatation.

PMID- 1397343
TI  - Prostacyclin is produced from endothelial cell-seeded grafts: an experimental
      study in sheep.
AB  - Endothelial cell seeding might be of value in reducing the thrombogenicity of
      small-diameter vascular grafts. We investigated the capacity of endothelial cell
      seeded grafts to produce prostacyclin and compared this with that of the unseeded
      graft as well as the native artery. Twelve sheep were operated on with carotid
      interposition of externally supported knitted dacron grafts. On one side of the
      neck the graft was seeded with endothelial cells, enzymatically harvested from
      the left jugular vein. After 3 weeks, three out of 12 seeded grafts, and one out
      of 12 unseeded grafts were occluded (N.S.). After excision, the grafts were
      mounted and perfused ex vivo for five 15-min periods. During the last period,
      arachidonic acid (4 micrograms/ml) was added to the perfusate. The resected
      carotid artery was used as a control. Prostacyclin was determined as the stable
      degradation product 6-keto-PGF1 alpha using radio-immunoassay, and expressed as
      pg mm-2 luminal surface. The native artery had a significantly higher release of
      prostacyclin than the seeded graft, which in turn had a significantly higher
      release than the unseeded graft. Histological examination showed weakly positive
      staining for factor VIII-related antigen on the luminal surface of seeded grafts.
      Scanning electron microscopy showed endothelial cells with typical endothelial
      tufts and was evaluated blindly from 10 areas of each graft. The extent of
      endothelial cell coverage was evaluated and scored from 0 to 2.5. The median
      score for the unseeded grafts was 0.3 and for the seeded grafts 1.5 (p = 0.008).
      Prostacyclin production was higher in seeded than unseeded grafts, but did not
      influence patency in this model.

PMID- 1397344
TI  - Revascularisation of distal tibial and pedal arteries.
AB  - The results of 1062 reconstructive operations performed on the tibial and
      peroneal arteries in patients with Fontaine stage III or stage IV disease are
      presented. A group of 121 patients in whom the anastomosis was to the tibial or
      peroneal artery with no direct flow to the foot, and a group of 59 patients with
      direct anastomoses to the pedal arteries, are analysed in detail.

PMID- 1397345
TI  - The aetiology of vein graft strictures: a prospective marker study.
AB  - In a prospective series of 74 femoro-popliteal vein grafts (34 in situ and 40
      reversed), 22 strictures were identified by duplex scanning in 18 grafts (24.3%).
      Thirteen strictures were identified in 10 of 40 reversed grafts and 9 strictures
      were identified in 8 of 34 in situ grafts. Grafts were marked at operation using
      surgical clips at sites of all valves, tributaries, clamps and venotomies, since
      these have all been suggested as potential sources of graft strictures. These
      were prospectively studied as part of a detailed graft surveillance programme by
      intravenous digital subtraction angiography and duplex scanning. A total of 377
      valves, 681 tributaries, 15 clamps and 2 venotomies were identified. Twenty-two
      strictures were detected in 18 grafts, an incidence of 24.3%, but only one
      lesions coincided with a specific marked area (a valve site). Duplex examination
      in 34 in situ grafts identified 10 residual valve cusps in seven grafts. In none
      of these was there any evidence of turbulence or flow disturbance, and none
      progressed to form a stricture. It is concluded that there is no correlation
      between valve sites, tributaries, clamp sites or residual valve cusps and the
      development of vein graft strictures.

PMID- 1397346
TI  - The morphology of recurrent varicose veins.
AB  - Over an 18-month period, of 444 patients referred for treatment for varicose
      veins, 95 (21%) had had previous surgery. By means of clinical hand-held Doppler
      and in selected venographic evaluation these were subdivided into three groups as
      follows. Type 1:29 of the 95 patients had recurrence through thigh perforators.
      Type 2:10 patients had developed incompetence through a second saphenous system,
      in nine of the 10 in the short saphenous having had previous long saphenous
      surgery. Type 3:46 patients had recurrent sapheno-femoral incompetence and 10
      sapheno-popliteal incompetence. A persistent long saphenous trunk in the thigh
      was present in approximately two-thirds of cases of types 1 and 3. In over half
      of the type 3 patients saphenofemoral recurrence was by reconstitution of the
      junction by neovascularisation. These morphological studies demonstrate why there
      may be an increased risk of recurrence if the long saphenous trunk is not excised
      at the time of primary surgery.

PMID- 1397347
TI  - Intraoperative prediction of ischaemic injury of the bowel: a comparison of laser
      Doppler flowmetry and tissue oximetry to histological analysis.
AB  - Intraoperative diagnosis of inadequate colonic perfusion would contribute to
      prevention of ischaemic colitis after abdominal aortic reconstructions. The aim
      of this study was to evaluate laser Doppler flowmetry (LDF) and tissue oximetry
      (TpO2) as predictors of the development of bowel necrosis. Devascularised loops
      of colon and ileum in anaesthetised pigs were divided into 10-20 mm segments and
      measurements of laser Doppler flux and TpO2 were performed in each segment. After
      7 h of ischaemia the segments were resected for histological and biochemical
      analysis. In 65 colonic and 58 ileal segments a significantly lower flux was
      found in segments with necrosis of greater than or equal to 30% of the mucosal
      thickness compared to segments with necrosis of less than or equal to 10% (p less
      than 0.01). The discriminant flux value was 50 perfusion units, confirming a
      previous clinical study. The specificity was 0.96 and the sensitivity 0.94. Flux
      was inversely correlated to tissue lactate concentration. Significantly lower
      TpO2 was found in 19 colonic segments with necrosis of greater than or equal to
      30% of mucosa compared to 19 colonic segments with necrosis of less than or equal
      to 10% (p less than 0.01). Using a discriminant value of 5kPa, a specificity of
      0.79, and a sensitivity of 0.95 were calculated. In 27 ileum segments no
      significant difference in TpO2 between different histological groups was found (p
      greater than 0.30). The results show that LDF and TpO2 can predict ischaemic
      injury of the colon, and LDF also of the small bowel.

PMID- 1397348
TI  - The relevance of posturally induced microvascular constriction after
      revascularisation in patients with chronic leg ischaemia.
AB  - In patients with severe chronic lower limb ischaemia, postural vasoconstriction
      is disturbed, resulting in enhanced skin microcirculatory perfusion on leg
      dependency. After vascular reconstructive surgery, postoperative oedema formation
      is frequently seen. In 31 patients with leg ischaemia undergoing
      revascularisation we investigated whether and, if so, for how long after surgery
      postural vasoconstriction would take to recover, and whether disturbed
      vasoconstriction correlates with the occurrence of postoperative oedema.
      Capillary microscopy and laser Doppler fluxmetry were used to assess nutritional
      and total skin perfusion, respectively. The measurements were performed before
      and up to 37 days after surgery. After revascularisation, the mean ankle blood
      pressure index rose from 40 to 82%. All patients, except those with persistently
      disturbed vasoconstriction showed improved microcirculatory parameters. Postural
      vasoconstriction was restored in 24 patients, occurring approximately on the
      eighth postoperative day. All patients who failed to recover vasoconstriction
      developed postoperative oedema. This study shows that the disturbance in postural
      vasoconstriction can be reversible, probably due to recovery of arteriolar smooth
      muscle tone, and that patients with persistently disturbed postural
      vasoconstriction, are prone to develop postoperative oedema.

PMID- 1397349
TI  - In situ saphenous vein bypass surgery in diabetic patients.
AB  - From 1986 through to 1990 a total of 483 consecutive in situ infra-inguinal vein
      bypass procedures were performed in 444 patients, of whom 112 (25%) were
      diabetics (57 insulin dependent diabetes mellitus and 55 non-insulin-dependent
      diabetes mellitus). Based on a prospective vascular data registry this material
      was analysed to determine the influence of diabetes on the outcome. Preoperative
      risk factors were equally distributed among diabetic and non-diabetic patients,
      except for smoking habits (diabetics: 48%; non-diabetics: 64%, p = 0.002) and
      cardiac disease (diabetics: 45%; non-diabetics: 29%, p = 0.005). Indication for
      surgery was gangrene or ulceration in 57% of diabetics, as opposed to 36% in non
      diabetic patients (p = 0.0002). A femoro-popliteal bypass was performed in 18% of
      patients, whereas 82% received an infrapopliteal procedure, of which 42% were to
      the distal third of the calf or foot. Diabetic patients had a significantly lower
      distal anastomosis than non-diabetic patients (p = 0.0001). The overall 3-year
      primary and secondary patency rates were 58 and 64%, respectively, with no
      differences between non-diabetics, non-insulin-dependent diabetics and insulin
      dependent diabetics. Neither did limb survival differ among the three groups.
      However, the rate of minor amputations was significantly higher in insulin
      dependent compared with non-insulin-dependent diabetics, who in turn had a higher
      rate than non-diabetic patients (p less than 0.00001). A markedly decreased
      survival rate was found in diabetics (p less than 0.0005).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1397350
TI  - The importance of vascular surgical audit to surgeons, patients and purchasers.
AB  - This audit of vascular surgical operations from a Teaching Hospital vascular unit
      was facilitated by computerised data collection. A total of 2075 patients had
      2628 procedures over the 6-year period 1985-1990. Vascular workload increased by
      50% to almost 350 primary reconstructions per year. In Bristol, vascular patients
      now occupy 19% of surgical bed-days. Mean stay for vascular patients is twice as
      long as for general surgical patients (14 days vs. 6 days) and three times as
      long for patients having secondary reconstructions (18 days) or those with
      critical limb ischaemia (21 days). Mortality and reoperation rates remained
      relatively constant throughout the study period. The overall mortality rate was
      10.4%, being highest for ruptured aortic aneurysms (31.9%) and lowest for carotid
      endarterectomy (1.7%). Early reoperation for the complications of vascular
      reconstruction was required in 9.1% cases, being most frequent for femoro-tibial
      grafts (26.1%) and least for carotid endarterectomy (1.7%). Vascular surgery is
      expensive, time consuming and on the increase in Bristol. Comprehensive
      computerised audit of vascular operating is essential both for patients who
      benefit from the maintenance of high standards, and also for surgeons whose
      results this year will determine the cost and volume of next year's contracts.

PMID- 1397351
TI  - Re-intervention after vascular surgery for critical leg ischaemia.
AB  - Re-operation after arterial bypass in the leg is common, may be seen as failure
      by many and can appear expensive to budget holders. Secondary reconstruction may
      not be undertaken for these reasons. The indications for and outcome of further
      intervention have been studied in 395 primary presentations with critical leg
      ischaemia, all of whom underwent arterial reconstruction. During the study period
      the primary amputation rate was 3%, and 10% of reconstructed patients presented
      with skin necrosis or gangrene. One hundred and twenty-nine reconstructions (32%)
      were to crural vessels in the lower third of the calf. Mean follow-up was 3
      years, 1 month mortality was 2% and overall mortality 20%. One hundred and
      seventy-three (44%) patients required further intervention: 118 (30%) for
      recurrence of ipsilateral ischaemic symptoms and 55 (14%) in the presence of a
      patent primary graft (mostly operations on the contralateral leg). A total of 695
      secondary operations were required over follow-up, a mean 1.75 additional
      operations per patient per 3 years. Following recurrence of ischaemia, graft
      revision or secondary revascularisation was undertaken in 98 of 118 (84%) legs
      whilst the remaining 19 legs had an amputation performed after primary graft
      failure. Secondary reconstruction was successful in salvaging 63 limbs to mean
      follow-up, a 64% success rate from revisional surgery. At mean follow-up 339 of
      395 limbs remain viable (86% limb salvage), secondary graft patency is 79% and
      primary graft patency 63%. Failure to re-intervene after primary graft failure
      would reduce limb salvage at 3 years to 70% with corresponding loss of 63
      legs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397352
TI  - The management of small abdominal aortic aneurysms: a computer simulation using
      Monte Carlo methods.
AB  - Many small abdominal aortic aneurysms can now be identified by ultrasound
      screening and it is necessary to decide whether the risks of enlargement and
      rupture justify elective surgery. A computer simulation of the behaviour of small
      aneurysms has been constructed using Monte Carlo methods to model patterns of
      enlargement and rupture. The effect of policy with regard to the observation and
      timing of intervention has been evaluated for different patient groups. The
      results demonstrate the value of early intervention in otherwise fit patients
      with expected operative mortality rates of 5% or below, whereas, for older
      patients (over 70 years old) 6-monthly screening and operation if the aneurysm
      exceeds 5 cm is suggested. Higher risk patients with expected operative mortality
      of over 10% may be better treated conservatively up to an aneurysm diameter of 7
      or 8 cm. The method used for simulation is flexible, being easily adjusted to
      take account of new information, and may have applications in other areas of
      clinical decision making.

PMID- 1397353
TI  - Endoscopic transthoracic sympathectomy: experience in the south west of England.
AB  - Thoracic sympathectomy has an established role in the management of primary
      palmar and axillary hyperhidrosis, Raynaud's phenomenon and occlusive vascular
      disease. Potential problems with traditional surgical approaches to the
      sympathetic chain include poor exposure, risk of damage to adjacent structures
      and postoperative pain. A minimally invasive endoscopic approach helps to
      overcome these problems. Using this technique, 45 procedures have been performed
      on 26 patients in two districts in the South West of England over the past five
      years. Follow-up information was available for 39 procedures. All 27 procedures
      for hyperhidrosis and both for occlusive vascular disease have produced a long
      term improvement. Nine of the 10 procedures for Raynaud's phenomenon have also
      produced some degree of long-term improvement. Complications included four
      asymptomatic pneumothoraces, two patients with temporary unilateral Horner's
      syndrome and two instances of intercosto-brachial numbness. On the positive side,
      patients expressed satisfaction with the efficacy, rapid recovery and small
      unobtrusive scars produced by the procedure. Endoscopic transthoracic
      sympathectomy is effective, safe and well accepted by patients and we believe is
      now the method of choice for this procedure.

PMID- 1397354
TI  - A head box to protect transcranial Doppler transducers during carotid surgery.

PMID- 1397355
TI  - Gas gangrene following intra-arterial injection of oral medication in a drug
      abuser.
AB  - We report a patient in whom intra-arterial injection of oral medication led to
      the development of fulminating gas gangrene and death, despite the initial
      clinical symptoms being minor. We believe that prophylactic antibiotics should be
      administered to patients following intra-arterial injection of oral medication
      especially if immunocompetence, such as from human immunodeficiency virus (HIV)
      infection, is likely.

PMID- 1397356
TI  - Peritonitis causing acute limb ischaemia.
AB  - A patient presented with an acutely ischaemic leg and mild abdominal pain.
      Arteriography showed an iliac occlusion and some distal occlusive disease. At
      laparotomy a perforated gastric ulcer was found, and by the end of this operation
      the foot was well perfused. This case exemplifies the serious reduction in limb
      blood supply which can be caused by an acute illness, without thrombosis of
      vessels. It emphasises the importance of general assessment and treatment of any
      associated acute condition, in cases of acute limb ischaemia.

PMID- 1397357
TI  - [Diphtheria].

PMID- 1397358
TI  - [The effect of harmful factors on the fetus].

PMID- 1397359
TI  - [The examination of women with menstrual cycle disorders].

PMID- 1397360
TI  - [The conditions for decreasing the risk and increasing the efficacy of infusion
      therapy].

PMID- 1397361
TI  - [The radiodiagnosis of the bone changes in a lower extremity stump].

PMID- 1397362
TI  - [The characteristics of trauma in motorcyclists].

PMID- 1397363
TI  - [Medical first aid for victims with separation of segments of the extremities].

PMID- 1397364
TI  - [The changeover of public health institutions to economic management methods
      under the conditions of the transition of this branch to the principles of
      medical insurance].

PMID- 1397365
TI  - [Dr. Berle wins the prize].

PMID- 1397366
TI  - Guidelines for human embryology laboratories. The American Fertility Society.

PMID- 1397368
TI  - American Nurses Association endorses Clinton/Gore ticket.

PMID- 1397367
TI  - Guidelines for human andrology laboratories. The American Fertility Society.

PMID- 1397369
TI  - FNA responds as hurricane Andrew hits South Florida.

PMID- 1397370
TI  - The legal regulation of nursing practice.

PMID- 1397371
TI  - Third party reimbursement: Part II. Medicare.

PMID- 1397372
TI  - About nurse anesthesia.

PMID- 1397373
TI  - Assisted living--an alternate choice.

PMID- 1397374
TI  - Correctional nursing: protective barrier for our communities.

PMID- 1397375
TI  - Advance directives--blessing or burden?

PMID- 1397376
TI  - The ethics of care: agency nurses are people too.

PMID- 1397377
TI  - Enhance nursing through professionalism.

PMID- 1397379
TI  - Discard nursing stereotype image.

PMID- 1397378
TI  - UCF students reach out through community project.

PMID- 1397380
TI  - After graduation.

PMID- 1397381
TI  - Preschool vision screening: FNSA resolution to be implemented.

PMID- 1397383
TI  - [Biology of trophoblast and its endocrinological profiles].
AB  - The trophoblast of human placenta is composed of syncytiotrophoblast (S-cell) and
      cytotrophoblast (C-cell). C-cell displays proliferative properties, while S-cell
      displays little potential for proliferation. A close similarity between cytologic
      localization of myc product and [3H]thymidine labeling suggests that myc
      expression is linked to trophoblast proliferation. In situ hybridization with
      cDNA probes revealed that mRNA expression of hCG alpha and hCG beta are initiated
      before syncytial formation, whereas hPL mRNA is expressed only in fully
      differentiated S-cell. EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were
      localized to C-cell, whereas EGF and EGF-R in 6-12 weeks placenta were localized
      to S-cell. Consistent with these findings, EGF exerted gestational age dependent
      dual action on early placenta: one was to stimulate trophoblast proliferation in
      4-5 weeks placenta and the other was to stimulate differentiated trophoblast
      function in 6-12 weeks placenta. An optimal dose of thyroid hormone stimulated
      progesterone, estradiol, hCG and hPL production in early placental tissues.
      Furthermore, women with unfavorable outcome of threatened abortion had lower T4,
      T3, free T4 and free T3 levels, as compared to women with favorable outcome.
      These data imply a role for thyroid hormone in maintaining early pregnancy. On
      the other hand, progesterone selectively inhibited hCG (alpha, beta) mRNAs
      expression and decreased hCG secretion in normal placental tissues, whereas
      choriocarcinoma did not respond to progesterone. This suggests that inhibitory
      regulation of hCG synthesis in choriocarcinoma is different from normal placenta.
      Characterization of choriocarcinoma hCG revealed that there are striking
      differences in carbohydrate structures between normal hCG and choriocarcinoma
      hCG. Sialic acid content in choriocarcinoma hCG was extremely lower compared to
      that in normal hCG. The biochemical detection of the alteration in hCG sugar
      chains is useful for early diagnosis of choriocarcinoma.

PMID- 1397382
TI  - [Treatment of pituitary adenomas].
AB  - There has been a dramatic development in the treatment of pituitary adenomas
      during the last two decades. The main factors which led to this development were
      the introduction of transsphenoidal surgery, the development of new imaging
      modalities such as computed tomography (CT) and magnetic resonance imaging (MRI)
      and the introduction of newer dopaminergic agents. Present status of the
      treatment of pituitary adenoma is reported here. This report is based on the
      experiences of 381 cases of pituitary adenomas treated at the Department of
      Neurosurgery, Hiroshima University School of Medicine within the last 16 years.
      There are some problems which have to be solved in order to achieve further
      development in the treatment of pituitary adenomas. Our experience in this field
      and a need for future development are listed below. 1) The transsphenoidal
      adenomectomy gives high cure rates in cases of micro and expansive prolactinomas
      and growth hormone secreting adenomas. 2) Results of the transsphenoidal surgery
      in cases of ACTH secreting adenomas is not satisfactory. In order to get higher
      cure rate, a more elaborate operative techniques and an introduction of more
      effective drug therapy are needed. 3) Further safety and curability in pituitary
      surgery will be achieved by the exploitation of new imaging modalities such as
      MRI.

PMID- 1397384
TI  - [Identification of a 3' splice site mutation in the thyroglobulin gene in a case
      of congenital familial goiter].
AB  - A case of congenital familial goiter with impaired thyroglobulin (Tg) synthesis
      has been reported. The patient is the fifth in a family of six children, three of
      whom have a goiter. The parents are cousins. The patient's thyroid function tests
      showed low T4 (1.0 microgram g/dl) and free T4 (0.2 ng/dl), normal or slightly
      increased T3 (1.8 ng/ml) and free T3 (7.4 pg/ml), and high TSH (57 micrograms
      U/ml). Serum Tg was 5.1 ng/ml (normal less than 30). The thyroidal 123I-uptake
      was 59.8% before and 54.5% after perchlorate test. Gel filtration with Bio-Gel A
      5m demonstrated the presence of albumin-like protein probably iodinated as a
      major protein in the thyroid and very low content of Tg which was smaller than
      the normal 19S Tg. Histologically microfollicular adenoma and negative Tg
      immunostaining were the dominant findings. Segregation of Tg alleles in the
      family was studied by Southern blotting with a probe revealing a diallelic RFLP.
      The results demonstrated that the affected siblings had received the same alleles
      from both parents and were homozygous for the RFLP. Northern blotting analysis of
      the goiter RNA with a Tg probe revealed that, whereas the amount of Tg mRNA was
      normal, its size seemed slightly reduced. PCR amplification of Tg mRNA as six
      overlapping cDNA fragments demonstrated that a 200bp fragment was missing from
      the 5' region of the goiter mRNA. Subcloning and sequencing of the cDNA
      fragments, and of the patient's genomic DNA amplified from this region, revealed
      that this aberrant splicing is due to a cytosine to guanine transversion at
      position minus 3 in the acceptor splice site of intron 3. The presence in exon 4
      of a putative donor tyrosine residue (tyr 130) involved in thyroid hormone
      formation provides a coherent explanation of the hypothyroid status of the
      patient. To our knowledge, this is the first identified mutation responsible for
      congenital familial goiter in humans.

PMID- 1397385
TI  - [Metastatic carcinoma of the sigmoid colon to the thyroid gland].
AB  - A case of metastatic thyroid cancer from sigmoid colon cancer is presented. A 52
      year-old woman had a sigmoidectomy due to adenocarcinoma of the sigmoid colon in
      April 1988. Serum carcinoembryonic antigen (CEA) levels gradually rose from July
      1990 along with multiple metastatic lesions which appeared in the lung. They were
      resected in January 1991. Two months later the subject noticed a painless and
      firm lump on the left anterior neck. She was found to have a solitary mass in the
      left thyroid lobe. Thyroid function remained within normal range. Cytological
      findings obtained by fine-needle aspiration biopsy showed tall columnar carcinoma
      cells with an acinar pattern. Subtotal thyroidectomy was performed, and
      histological examination revealed metastatic adenocarcinoma from colon cancer.
      Immunohistochemical staining by anti-CEA was positive but anti-thyroglobulin was
      negative.

PMID- 1397386
TI  - [Characterization of thyroglobulin in a patient with functioning and non
      functioning benign thyroid tumors].
AB  - The chemical and immunological properties of thyroglobulin (Tg) in tissue
      obtained from a patient co-existed with two types of thyroid tumors, i.e.,
      functioning and non-functioning, and were compared with the properties of Tg that
      was isolated from adjacent peripheral tissue. In the present observations, the Tg
      content was markedly increased in the non-functioning thyroid tumor. On the other
      hand, the Tg content in the functioning tumor was at the normal level. The iodine
      content of Tg was significantly lower in the non-functioning tumor than in
      peripheral tissues. Affinity with Lectins differed among Tg preparations,
      suggesting that the carbohydrate chain in the Tg was different in each nodule in
      a single individual.

PMID- 1397387
TI  - Relationship between dietary retinol and alpha-tocopherol and lipid peroxidation
      in rat liver cytosol.
AB  - The effects of retinol and alpha-tocopherol-deficient and supplemented diets on
      the cytosolic concentration of thiobarbituric acid reactive substances (TBARS) in
      rat liver have been studied. Physiological lipoperoxidation (LPO) was observed in
      liver cytosol of control rats (TBARS = 0.315 +/- 0.034 nmol of MDA equivalents/mg
      of liver cytosolic proteins). In retinol-deficient diets there was a decrease in
      retinolaemia and the absence of retinol in liver cytosol while cytosolic TBARS
      increased significantly (P less than 0.001). Vitamin E was not found in cytosolic
      fractions, except in alpha-tocopherol-supplemented diet rats. alpha-Tocopherol
      deficient diets induced an absence of vitamin E in the serum and cytosolic TBARS
      were increased compared to controls (P less than 0.001). Supplementation of the
      diet with retinol and alpha-tocopherol or both in combination induced a
      significant decrease in liver cytosolic TBARS (P less than 0.001). Finally the
      combination of low dietary supplementation with retinol and alpha-tocopherol (ten
      times the normal diet each) induced the maximum anti-LPO effect.

PMID- 1397388
TI  - An improved olive oil overall migration test for plastics using Karl Fischer
      titration.
AB  - Karl Fischer titration has been used to eliminate the need to humidity-condition
      food contact plastics under test for overall migration into olive oil. The water
      content of the oil is measured before and after the migration test. This direct
      measure of the loss (or uptake) of water by the test plastic is then used in
      calculations of the overall migration. The use of Karl Fischer titration gives
      faster analysis with reduced labour input. The time savings varied from a few
      days to several weeks depending on the type of plastic. Karl Fischer titration is
      particularly useful in the high temperature testing of polar plastics where
      incomplete humidity conditioning can lead to erroneous results. The technique
      should be equally valuable when employing sunflower oil or the triglyceride HB307
      in place of olive oil.

PMID- 1397389
TI  - The effect of microwave energy on specific migration from food contact plastics.
AB  - Experiments have been carried out with (a) microwave treatment of plastics
      followed by migration testing using the food simulant, olive oil, and (b)
      microwave treatment of plastics in direct contact with an organic extractant (iso
      octane). In neither of these complementary approaches was there evidence of any
      difference in migration from plastics that had been microwave-treated compared
      with plastics that had received an equivalent thermal treatment. Five plastics
      commonly employed in microwave applications were tested and oligomers,
      plasticizer, antioxidant and volatile contaminants were monitored as
      representatives of typical migration species.

PMID- 1397390
TI  - N-nitrosamine and mutagenicity formation in Chinese salted fish after digestion.
AB  - Salted and dried fish (Nemipterus virgatus), acquired from Hong Kong, was treated
      with 0.43-110 mM nitrite during in vitro digestion using gastric enzymes and the
      volatile N-nitrosamine content and mutagenicity on Salmonella typhimurium TA100
      assayed without concentration. N-Nitrosodimethylamine (NDMA; the only nitrosamine
      detected) formation was second order in nitrite concentration. When 10 g of fish
      was treated with 6.96 mM nitrite, 394 nM NDMA was formed. Thiocyanate was
      catalytic for NDMA formation at nitrite concentration greater than 0.87 mM and
      when the ratio of thiocyanate to nitrite was greater than 1. Approximately a 50%
      inhibition in NDMA formation by ascorbic acid was seen when the ratio of
      ascorbate to nitrite was approximately 2 or greater and the nitrite concentration
      was 1.74 mM. Mutagenicity increased with increasing nitrite concentration but the
      addition of thiocyanate did not increase mutagenicity over nitrite alone.
      Ascorbate increased mutagenicity even though NDMA formation was inhibited. Even
      at nitrite concentrations greater than 100-fold higher than expected in vivo,
      there was insufficient NDMA formed to account for the observed mutagenicity.
      These data do not exclude the possibility that the observed mutagenicity was due
      to non-volatile N-nitroso compounds, however, this possibility seems unlikely
      given the effects of ascorbate and thiocyanate which would be expected to inhibit
      and enhance non-volatile N-nitroso compound formation.

PMID- 1397392
TI  - Deoxynivalenol in wheat and maize flour reference materials. 1. An
      intercomparison of methods.
AB  - To provide a basis for the certification of wheat and maize flour reference
      materials containing deoxynivalenol, a series of three preliminary
      intercomparisons of methods was carried out between 1985 and 1988. The first
      intercomparison, involving 10 laboratories was designed to examine the
      determinative step and used a solution of deoxynivalenol in ethyl acetate and a
      spiked wheat extract solution. The second intercomparison involving 13
      laboratories established minimum extraction times for naturally contaminated
      samples, demonstrated the absence of matrix effects in purified extracts and
      showed that there was no evidence of differences in the use of any of three
      different end determinations. The third intercomparison involving 15 laboratories
      used naturally contaminated cereals and acted as a preliminary to the final
      certification exercise. Over a period of four years there was a steady
      improvement in the range of results submitted by participants thought to be due
      to the application of improved analytical methods, increased expertise in the
      analysis and through experience gained through the intercomparisons.

PMID- 1397391
TI  - Review of the occurrence and formation of non-volatile N-nitroso compounds in
      foods.
AB  - A review of the literature published prior to July 1991 covers the occurrence and
      formation of non-volatile N-nitrosamines occurring in foods and beverages. The
      presence of identified volatile and non-volatile N-nitrosamines accounts for less
      than 10% of the total apparent N-nitrosamine concentration. N-Nitrosoproline and
      N-nitrosothiazolidine-4-carboxylic acid are the most commonly identified non
      volatile N-nitrosamines in the diet. Non-volatile N-nitrosamines account for 12
      of the 21 currently identified N-nitroso compounds in foods and beverages.

PMID- 1397393
TI  - Tetrahydro-beta-carboline carboxylic acids in smoked foods.
AB  - This paper reports for the first time in smoked foods the presence of three
      tetrahydro-beta-carboline carboxylic acids. One of these, 1-hydroxymethyl
      tetrahydro-beta-carboline-3-carboxylic acid, which is derived from the
      interaction of tryptophan and glycolaldehyde, and which has not previously been
      reported in foods, was observed in 20 samples at levels up to 444 micrograms/kg.
      The corresponding products which are derived from tryptophan and formaldehyde or
      tryptophan and acetaldehyde were found respectively in 28 samples at levels up to
      22 mg/kg and in 16 samples at levels up to 881 micrograms/kg. Greater
      concentrations were generally found in those smoked foods having a lower pH value
      and produced by using a longer fermentation or maturation. Only 1-methyl
      tetrahydro-beta-carboline carboxylic acid (156-574 micrograms/kg) was found in
      the four unsmoked samples analysed.

PMID- 1397394
TI  - A preliminary study of the bioavailability of iron- and zinc-glycine chelates.
AB  - Groups of rats were fed diets containing marginal levels of Fe and Zn as glycine
      chelates (tradename 'Chelazome', Albion Laboratories, Verona, New Jersey, USA),
      or the same level of mineral as ferrous sulphate or zinc carbonate. The Fe diets
      were fed to weanling rats for 4 weeks and the Zn diets to young adult rats for 5
      weeks. Blood Hb concentrations were significantly higher in the group fed Fe
      chelazome than ferrous sulphate, 149 and 128 g/l respectively (P less than
      0.001), but PCV and liver Fe concentrations were similar between the two groups.
      No difference in plasma Zn, pancreas, testes or femur Zn concentrations were
      observed between the two Zn groups, indicating that Zn-chelazome has no advantage
      over zinc carbonate. The results of this preliminary study indicate that Fe
      chelazome has a higher bioavailability than ferrous sulphate and merits further
      study.

PMID- 1397395
TI  - Studies into the transfer and migration of phthalate esters from aluminium foil
      paper laminates to butter and margarine.
AB  - Retail samples of Canadian butter and margarine wrapped in aluminium foil-paper
      laminate were found to contain dibutyl, butyl benzyl and/or di-2-ethylhexyl
      phthalate (DBP, BBP, DEHP) as packaging migrants at levels up to 10.6, 47.8 and
      11.9 micrograms/g, respectively. These phthalates were determined by capillary
      gas chromatography with flame ionization detection (GC-FID) after clean-up of the
      separated oil by sweep co-distillation. The phthalate esters found in the
      contacted butter or margarine were also found in the contacting wrappers. They
      were determined in wrapper extracts by liquid chromatography with diode array
      detection or by GC-FID. Analysis of unused wrappers showed 76-88% of the total
      DBP and DEHP to be present on the foil (outer) surface as a component of the
      protective coating (washcoat). The remainder of the DBP and DEHP was found on the
      food-contacting paper surface, presumably by transfer from the outer to inner
      surface during storage in tightly wound rolls, although transfer of phthalate
      esters, if present in the paper-foil adhesive, cannot be ruled out. Food
      contacting surface concentrations of DBP and DEHP were found to be 2.4 to 4.7 and
      2.8 to 3.6 micrograms/cm2, respectively. Samples of each packaging component:
      paper, foil, adhesive, washcoat and inks were analysed for phthalate esters and
      only the washcoat was found to contain phthalate esters.

PMID- 1397396
TI  - Leaching of aluminium from aluminium dishes and packages.
AB  - A study was carried out of the leaching of aluminium from aluminium cooking
      vessels and packages. Very small or undetectable levels of aluminium leached from
      packaging materials into foodstuffs. In boiling tests with neutral porridge no
      migration of aluminium into the test matrix was observed from the pan. When
      boiling milk, the leaching of aluminium was 0.2-0.8 mg/kg. The aluminium content
      of tap water in aluminium pans when reaching boiling point was 0.54-4.3 mg/l and
      increased with increasing boiling time to 6.3-17 mg/l. Aluminium dissolved in
      foods based on acidic fruit juice rose to levels of 2.9-35 mg/kg when the foods
      were boiled in aluminium pans. Steaming of currant berries in an aluminium vessel
      gave aluminium concentrations of 19-77 mg/kg in the resulting juice. The highest
      aluminium concentration of 170 mg/kg was measured in rhubarb juice prepared in
      the steaming vessel. Aluminium dissolved in water to levels of 0.81-1.4 mg/l when
      heated for the first time in new coffee percolators. The aluminium concentration
      of water heated in older percolators was 0.09-0.78 mg/l.

PMID- 1397397
TI  - Lead contamination during domestic preparation and cooking of potatoes and
      leaching of bone-derived lead on roasting, marinading and boiling beef.
AB  - Lead concentrations were measured in boiled, mashed potatoes and in baked
      potatoes that had been prepared and cooked in domestic kitchens. Levels of lead
      in the boiled, mashed potatoes ranged from below the 1 microgram/kg limit of
      detection up to 18 micrograms/kg with a mean of 6 micrograms/kg (wet weight). In
      the large majority of cases the lead in the tap water was the predominant source
      of the metal. Higher amounts of lead (range 11 micrograms/kg to 56 micrograms/kg,
      mean 27 micrograms/kg) were present in baked potatoes and this was attributed to
      soil adhering to the potato skin. The extent of leaching of lead from bone during
      cooking has also been investigated. For beef stocks there was little evidence to
      suggest that significant migration of bone lead occurred. For beef casseroles,
      marinaded in red wine, some leaching did occur from beef joints containing
      elevated amounts of bone lead; however the levels were all below 350
      micrograms/kg and, on average, less than double that found in casseroles prepared
      from normal joints where the bone lead levels were an order of magnitude less.

PMID- 1397398
TI  - Survey of animal livers for vitamin A content.
AB  - Retail samples of livers from calf (23), ox (18), lamb (17), pig (15), chicken
      (16) and turkey (1) were analysed to determine levels of vitamin A (all trans
      retinol) and to aid assessment of the effects of using vitamin supplemented
      compound feedingstuffs for livestock. For comparison, 22 liver samples from lambs
      reared on diets not containing vitamin-supplemented compound feedingstuffs and
      four samples of liver from ox which had received supplemented feed but not during
      the last four months prior to slaughter were also analysed. The chosen method of
      analysis utilized saponification, solvent extraction and normal-phase high
      performance liquid chromatography with fluorescence detection. For all species
      analysed, the levels of vitamin A ranged from 10 to 1100 mg/kg, with all but
      seven at or below 400 mg/kg. For lamb and ox livers, the mean levels were 310
      mg/kg and 200 mg/kg respectively for retail samples. The mean levels were 220
      mg/kg (lamb) and 120 mg/kg (ox) in liver samples from animals fed controlled
      diets. The results are of the same order as those reported over recent years.

PMID- 1397400
TI  - Total diet studies: the identification of core foods in the United States food
      supply.
AB  - Some total diet studies are based on the selection and analysis of core foods in
      a national or regional food supply. One way to select core foods is by
      computerized evaluation of the daily food intakes reported by subjects
      participating in national food consumption surveys. The foods consumed by the
      population groups of concern may be aggregated into core food groups. The foods
      within each group may be ranked according to daily intake and weight percentage
      of the total diet. The food that best represents each group may then be
      identified as a core food, and the daily consumption levels for each food group
      may then be assigned to the core food representing the group. Consumption levels
      may be determined for the specific age-sex categories of concern. To assess the
      representativeness of core foods identified in this manner, the food composition
      database of the national survey may be used to determine nutrient intakes based
      on the full range of foods in the database versus nutrient intakes based on the
      core foods.

PMID- 1397399
TI  - Comparison of HPTLC and HPLC procedures for the determination of certain
      xenobiotic residues in apples and pears.
AB  - HPTLC was used to check for residues of benomyl, carbendazim, ethoxyquin and
      thiabendazole in apples and pears. The method used showed good precision with a
      percentage coefficient of variation of less than 5%; recoveries were always
      greater than 90%. The limits of determination using HPTLC were always at least
      four times lower than Italian statutory limits. Selectivity with respect to other
      matrix components was excellent for all fruit varieties tested. Comparison with
      HPLC confirmed the validity of the results.

PMID- 1397401
TI  - Proposal for an international interface standard for food databases.
AB  - A database interface standard incorporating the food description language LANGUAL
      is under development to allow international exchange of food composition, food
      consumption, and other food-related data. The first step in this project is the
      refinement and implementation of a schema for the interface standard. This schema
      includes descriptive terms for LANGUAL factors and other aspects of foods. The
      second step is the development of a repertoire of personal computer programs for
      retrieval of food data, using the standard interface. The third step calls for
      the dissemination of the results of this project to an international audience
      through demonstration projects for international symposia and pilot tests for
      scientific applications.

PMID- 1397402
TI  - Malignant mesothelioma.

PMID- 1397404
TI  - Second antiviral drug approved for AIDS.

PMID- 1397403
TI  - Sensory symptoms of multiple sclerosis may be clues to causation: review and a
      hypothesis.
AB  - Sensory signs and symptoms occur in 75 percent of patients with multiple
      sclerosis (MS), ranking second to coordination defects. After intensive research
      into MS began in the 1930s, most attention was devoted to central nervous system
      demyelination. Some studies were done on peripheral nerve, but none on the
      sensory ganglia of the cord or brain. An original and thus far uninvestigated
      hypothesis is presented here that an unidentified organism might reside and
      multiply in various dorsal root and cranial sensory ganglia (DRG). This review
      summarizes the sensory signs and symptoms of multiple sclerosis, traces the
      embryology and physiology of DRG, and describes the present day research status
      of human demyelination produced by a number of viral infections. If the
      infectious agent for MS exists in a latent state in the DRG, low spinal fluid
      viral titers and sporadic cultures of certain viruses might be explained by the
      occasional contact of spinal and cranial sensory ganglia with spinal fluid flow.
      Research techniques available to test the hypothesis are as follows: various
      heating reactions and evoked potential testing of patients, and viral
      hybridization-transcription techniques applied to DRG obtained at autopsy. The
      "Decade of the Brain" became law on July 25, 1989, when President Bush signed
      Joint House Resolution 174. The forward looking declaration calls upon citizens
      and scientists alike to dedicate themselves for the next ten years to the task of
      eliminating various neuropsychiatric diseases that decimate many populations.
      High on the list is multiple sclerosis (MS), the subject of a new hypothesis
      presented here.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397405
TI  - School health talks program.

PMID- 1397406
TI  - Clinical applications of magnetic resonance angiography.
AB  - Recent technical advances in magnetic resonance imaging (MRI) now allow for the
      noninvasive study of blood flow in vessels, or magnetic resonance angiography
      (MRA). We describe several case reports involving the use of MRA and discuss its
      advantages in evaluating patients for carotid artery stenosis, intracerebral
      aneurysms, and arteriovenous malformations (AVMs).

PMID- 1397407
TI  - Laparoscopic cholecystectomy: the Medical Center of Delaware experience.

PMID- 1397408
TI  - Quality assurance and continuous quality improvement: history, current practice,
      and future directions.
AB  - Quality Assurance (QA) provides opportunities for physicians and allied health
      professionals to improve patient care and disease outcomes. Its goals are
      increased efficiency and efficacy in healthcare. QA activities are based upon
      objective criteria and systematic review and make important contributions to the
      effectiveness of hospitals and other care facilities. Successful programs help to
      maximize health status of patients while minimizing resource utilization.
      Beginning in 1917, early QA efforts were often informal and subjective but now
      include standards for QA and strategies for monitoring and evaluating patient
      care. Central to its new "Agenda for Change," the Joint Commission on
      Accreditation of Healthcare Organizations has embraced the concept of continuous
      quality improvement (CQI). This moves the focus of review away from department-
      or practitioner-specific activities and toward a "systems" form of evaluation.
      CQI is rooted in patient-care realities, is easy to implement, is based upon
      scientific assessments, and solves practical problems in an incremental and
      ongoing fashion.

PMID- 1397409
TI  - International Consensus Report urges changes in asthma treatment.

PMID- 1397410
TI  - Health care, right or privilege.

PMID- 1397411
TI  - School health talks program, 1992.

PMID- 1397412
TI  - Implementation of the Haemophilus B vaccine for infants by family physicians.
AB  - This study surveyed the members of the Department of Family Practice in a
      community hospital regarding the implementation of the newly recommended
      immunization protocol using Haemophilus Influenzae B Vaccine (HbOC) for infants
      at 2, 4, and 6 months of age. The purpose was to assess the ability of the
      physicians to alter their established practices in a timely fashion. The results
      show that initially 38/66 (58 percent) of the family physicians who care for
      infants and children were using the new vaccine already (eight to 10 weeks after
      FDA release). An additional 11 (17 percent) had begun using the vaccine by a
      second interview four weeks later. Another six (nine percent) responded to a call
      by a family practice resident. The remaining 16 percent preferred to await
      governmental regulations or did not respond to interview. Despite uncertain
      communications to family physicians in this community, the majority were aware of
      and adapted readily to new immunization recommendations. Prompt notification of
      all physicians regarding important new vaccine protocols can have a significant
      impact on the health of infants and children.

PMID- 1397413
TI  - Delaware Emergency Medical Services System: cardiac resuscitation.
AB  - The Delaware EMS system has been in existence for 20 years. Initially begun as
      one paramedic unit serving New Castle County, it now comprises 15 units in a
      statewide system. The goal of this report is to detail the EMS system's impact on
      prehospital cardiac resuscitation and airway management. Emergency Medical
      Services (EMS) encompass all aspects of managing a sick or injured patient prior
      to arrival to the hospital. From the time a patient dials 911 until they arrive
      in the care of a doctor in an emergency room, the EMS system provides initial
      medical evaluation and care as well as transportation to the hospital. The
      components of Delaware's EMS system include: 1. Bystanders--the public is often
      called upon to perform CPR until trained rescuers arrive. 2. Medical Dispatchers-
      they receive incoming 911 calls and determine the personnel needed. 3. First
      responders--ambulance crews trained in basic life support (BLS). 4. Second
      responders--ambulance crews trained in advanced life support (ALS), paramedics.
      5. Medical Control--doctors who are in radio contact with paramedics to provide
      medical advice.

PMID- 1397414
TI  - Physicians' office practice.

PMID- 1397415
TI  - Brain and central nervous system tumors Delaware, 1980 to 1989.

PMID- 1397416
TI  - Radiograph of the month. Adult supraglottitis (epiglottitis).

PMID- 1397417
TI  - Improving access to good medical care.

PMID- 1397418
TI  - Update on asthma: the Asthma Initiative.

PMID- 1397419
TI  - "Incidental hepatic hemangioma" reprised.

PMID- 1397420
TI  - More on "primary care physicians".

PMID- 1397421
TI  - Response to "Changes in community psychiatry during the past 50 years".

PMID- 1397422
TI  - U.S. doctors said to be hesitant on AIDS care.

PMID- 1397423
TI  - A preliminary diagnostic and treatment protocol.
AB  - The objectives of the preliminary diagnostic and treatment protocol are 1. To
      reveal retention or resistance form deficiencies. 2. To reveal need for
      augmentive periodontal crown-lengthening surgical procedures. 3. To evaluate
      pontic form for the existing space. 4. To preplan occlusal plane deficiencies and
      methods of corrective treatment to establish Curve of Spee. 5. To preplan
      occlusal scheme, i.e., canine guidance, group function, mutually protected
      occlusion, and cross-bite conditions. 6. To aid in preplanning sequence of
      treatment and method of preservation of occlusal vertical dimension. 7. To serve
      as a visual aid for discussion of treatment recommendations with patient prior to
      actual treatment. 8. To act as a medicolegal record to document the clinician's
      pretreatment planning in complex treatment situations for possible use in peer
      review or litigation. 9. To aid in fabrication of an elastomer reduction guide
      for use during crown preparation. 10. To aid in fabrication of a vacuum-formed
      template for provisional restoration of crown and abutment teeth after
      preparation.

PMID- 1397424
TI  - Comprehensive fixed prosthodontics.

PMID- 1397425
TI  - Clinical decision analysis in fixed prosthodontics.
AB  - Structured clinical decision analysis in dentistry in fixed prosthodontics, as in
      any branch of dentistry, allows the practitioner to think through more clearly
      the problems at hand based on the clinical data and extenuating factors presented
      by the patient. This discipline of decision making is intended to complement the
      experience level and educational background of the clinician in assisting him or
      her through the decision process. Additionally, CDA helps the clinician define
      not only the pre-existing condition of the patient prior to irreversible therapy,
      but also which treatment strategies may best be suited for that individual over
      an extended period. The systematic nature of decision analysis stimulates the
      focusing of one's attention on those factors considered to be germane to the
      overall complexity of the case and, at the same time, excluding those factors
      having little or no influence on its final outcome. With further implementation
      of computerized databases and procedural outcome probabilities based on clinical
      and laboratory studies as well as the clinical experience of those choosing to
      use it, the future for structured, formalized clinical decision analysis seems
      quite promising.

PMID- 1397426
TI  - Prosthetic rehabilitation in temporomandibular disorder and orofacial pain
      patients. Clinical problem solving.
AB  - Good clinical decision making represents an integral part of quality care. A
      definition of the dental problem and its significance from a dental point of
      view, in combination with a good working hypothesis of the nature of the
      concurrent TMD condition are prerequisites of any successful clinical problem
      solving. It is hoped that, with time, we will be in a position to call upon hard
      data on the probability and utility of successful outcome for each treatment
      alternative. This will bring the needed structure and scientific validity to a
      terribly complex albeit clinically important problem.

PMID- 1397427
TI  - Pontic design and localized ridge augmentation in fixed partial denture design.
AB  - The endpoint of fixed prosthesis design is an esthetic and functional pontic that
      is compatible with soft-tissue health. In the posterior segment, where esthetics
      is not as critical, a sanitary pontic form is most compatible with function and
      hygiene. In the maxillary anterior region, a properly contoured modified ridge
      lap pontic design constructed of glazed porcelain most readily fulfills both the
      esthetic and physiologic requirements. Although the ovate pontic form may satisfy
      esthetic demands to a greater degree, this is often at the expense of underlying
      soft-tissue health. In maxillary edentulous regions, ridge deformities may
      preclude a good pontic fit and esthetic result and dictate the need for surgical
      augmentation of the collapsed ridge. Selection of the appropriate surgical
      procedure and graft material depends on the nature and extent of the defect and
      availability of donor tissue. The subepithelial graft employing the tunnel
      approach is appropriate when augmentation in only a labial dimension is
      necessary. When the employing the trapdoor approach or full thickness gingival
      onlay graft may be employed. In large defects, sequential grafting procedures may
      be necessary to achieve the desired result. An esthetic and functional result can
      be attained through proper execution of an appropriate surgical technique and
      adherence to the principles of proper pontic design.

PMID- 1397428
TI  - Orthodontic adjunctive treatment in fixed prosthodontics.
AB  - The purpose of this article has been to increase the restorative dentist's
      appreciation for the rationale justifying preprosthodontic orthodontic treatment.
      It has not been intended to identify all the specific indications for the use of
      orthodontic treatment to enhance prosthodontic treatment nor has it been intended
      as a reference to assist the restorative dentist in placing and using orthodontic
      appliances. Figure 12 illustrates a typical case in which the combination of
      orthodontic and prosthodontic treatment resulted in a more favorable outcome than
      prosthodontic treatment alone. When planning prosthodontic treatment, the dentist
      should embrace a dynamic view of tooth position and determine whether restorative
      treatment can be enhanced by tooth movement. Improved tooth position can
      eliminate potentially pathologic occlusion and create a healthier periodontal
      environment that is easier to maintain. In addition, it permits the dentist to
      place restorations that often require less natural tooth reduction during
      preparation, and that are more esthetic, functional, stable, and durable.
      Orthodontic treatment that accomplishes these benefits may be limited to a
      partial fixed appliance localized to one segment of an arch or require a more
      extensive fixed appliance. Much of this treatment can be accomplished by the
      interested restorative dentist. Addressing more comprehensive orthodontic
      problems in patients requiring prosthodontic care is best managed through a
      restorative dentist and orthodontist team approach to treatment.

PMID- 1397429
TI  - Restoration of endodontically treated teeth.
AB  - Criteria have been presented for the evaluation of and treatment planning for
      endodontically treated teeth for final restoration. The dentist must consider the
      advantages and disadvantages of saving teeth according to their eventual role in
      restoring occlusal function, arch integrity, and esthetics. The prognosis is
      dependent on successful endodontic therapy, the presence of sound periodontal
      support, and an acceptable restorative effort. Currently accepted post and core
      systems and materials have been reviewed.

PMID- 1397430
TI  - Restoration of the vertical dimension of occlusion in the severely worn
      dentition.
AB  - The guidelines presented in this article for diagnosis and treatment of extreme
      tooth wear are not meant to be all inclusive. Every patient has unique treatment
      needs, and all of these needs may not be addressed specifically in this article.
      We believe, however, that careful adherence to the guidelines presented should
      facilitate a successful treatment of most if not all patients with moderate or
      severe tooth wear. The general guidelines for treatment of these patients include
      the following: 1. A comprehensive examination, including a thorough medical and
      dental history, orofacial and dental clinical examination, dental radiographs,
      TMD screening history and examination, impressions and jaw relation records for
      mounting casts in a semi-adjustable articulator, 2. A diagnostic wax-up and
      diagnostic occlusal adjustment on additional or duplicated mounted casts, 3.
      Careful planning and consultation regarding the need for preparatory treatment.
      Careful integration and sequencing of the different areas of treatment needed to
      enhance the finished result, 4. Discussion with the patient of the different
      treatment alternatives and sequences possible for his or her individual case,
      with presentation of advantages and disadvantages and prognosis for each, 5.
      Finally, careful execution of the agreed upon treatment plan by the dentist.
      Although not specifically mentioned, treatment success requires a highly
      motivated patient and skilled dental laboratory technicians. These "treatment
      partners" should be included in the planning stages of treatment as early as
      possible to enhance the possibility of having a successful treatment result.

PMID- 1397431
TI  - The clinical use of glass-ionomer cements.
AB  - The use of glass-ionomer cements in clinical dentistry has expanded greatly over
      the last decade. Their use in treating early carious or erosion lesions has been
      investigated widely and established techniques include fissure filling,
      restoration of erosion lesions without cavity preparation, and the internal or
      tunnel restoration. Because of their adhesion to moist tooth structure, biologic
      compatibility, and fluoride release, increasing use also has been made of their
      anticariogenic properties in treating geriatric patients. Glass-ionomers have
      proved very successful as dentin substitutes for attaching composites to enamel
      without involving risk of pulpal damage in the deeper cavity. The deficiencies of
      glass-ionomer cements are well known, including lack of toughness, early water
      sensitivity, low abrasion resistance, and porosity, leading to poor surface
      polish. Solving these problems is formidable because inherently the strength of
      these cements is related to their water content. The clinician should be aware of
      these deficiencies and stay within the parameters of the techniques outlined in
      this article. In particular, clinical success depends on early protection of the
      cement from hydration or dehydration and the current use of light-cured bonding
      agents largely has solved this problem. The future probably lies in using
      laminate techniques in which materials that attach to dentin and form a biologic
      seal can be covered by tougher and harder enamel veneers, thus mimicking the
      structure of the tooth. It is possible that future materials will be developed on
      the lines of these polyelectrolyte cements in which higher molecular weight
      polymers are used in conjunction with polymers that contain photoinitiators to
      effect light curing and toughen the matrix. In addition, the possibility of
      developing laboratory-cured glass-ionomer inlays in which porosity can be reduced
      and tougher polymers used should be considered.

PMID- 1397432
TI  - Esthetic and biomechanical considerations in reconstructions using dental
      implants.
AB  - The single-tooth implant-supported restoration can provide an outstanding service
      to many patients. It requires an understanding of the biomechanical principles
      involved and attention to the many details involved with the diagnosis and
      treatment planning for these restorations. The clinician should realize that this
      restorative approach is contraindicated in many circumstances. As Peter K. Thomas
      said, "Spend more time planning than doing and doing becomes easier."

PMID- 1397433
TI  - Alternative crown systems. Is the metal-ceramic crown always the restoration of
      choice?
AB  - The metal-ceramic crown system still is selected the most frequently because of
      its strength and versatility. The ability to select metals for color or strength
      for single units or fixed partial dentures gives great flexibility, but when
      esthetics of the anterior region are a prime concern, the all-ceramic crown is
      still an excellent choice. Choice of which all-ceramic system to use is dependent
      on the strength demands, esthetic needs, amount of tooth structure that can be
      preserved, and laboratory support available. Where good tooth structure remains
      but some color, contour, or incisal length changes are desired, the porcelain
      laminate veneer is an outstanding esthetic and restorative choice. When good
      labial tooth structure remains but lingual structure is inadequate, a partial
      veneer gold crown can be an excellent esthetic choice. If moderate tooth
      structure is lost or moderate staining is present, the Dicor crown is a superb
      choice. In those instances in which heavy staining is present, a foil or core
      system should be considered to completely block out the background colors. As the
      occlusal forces become more of a factor, selection of a restorative system will
      depend more on strength than esthetic demands. The aluminous porcelain jacket
      crown still offers great strength and esthetics at a reasonable price. When most
      of the color is on the surface of the teeth, or when there is a high translucency
      to the teeth, Dicor can provide very esthetic results, and the Dicor Plus crown
      offers the opportunity to develop intrinsic shading. When greater strength is
      required, selection of a foil and core system is suggested, as might be a system
      that provides a stronger core material, like Alceram or Inceram. These stronger
      core materials will render improved flexural and compressive strengths, but some
      increases in brightness may occur with the increased alumina content of the
      cores. The future in ceramic restorative dentistry may be in the computer
      generated crown if ways to develop internal coloring and layered building can be
      developed and cost can be controlled. Ceramic crowns are best limited to the
      anterior region of the mouth where occlusal forces normally are less than those
      found in the posterior region. In selected cases, in which there is no evidence
      of parafunctional habits, and when the dentist and technician are well versed in
      functional occlusion and have maximum restorative control of the occlusion,
      posterior ceramic restorations will be successful. It is important to remember in
      these cases that porcelain is harder than enamel and very strong in
      compression.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1397434
TI  - Fixed prosthodontics in the elderly population. Life expectancy of fixed
      restorations, failures, and retreatment methods.
AB  - The restorative needs of older dental patients challenge the ingenuity, anatomic
      knowledge, artistic skills, occlusal philosophies, and material knowledge of the
      clinician. Achieving the most secure foundation while simultaneously eliminating
      imperfections and incorporating a design that promotes good oral hygiene and a
      natural and attractive appearance are significant contributors to a patient's
      welfare. The treatment decision regarding fixed prosthodontics for elderly
      patients requires the balancing of two opposing arguments: 1. In patients who are
      older, and who are perhaps medically or physically compromised, and, in addition,
      who may be on a limited budget (or perceived limited budget), it is important to
      fabricate dental prostheses that are as good as possible to minimize the
      likelihood that the prosthesis will need to be remade in the future when the
      patient is likely to be even more compromised financially, medically, or
      physically, and also to minimize the stress on the patient of accommodating to
      something that is less than an optimal dental solution. 2. Patients in this age
      group often anticipate financial strain in the future, perhaps realistically in
      view of the increasing percent of older adults who are institutionalized (5% of
      persons 65 years old or older, 20% of persons 80 years old or older). Also, many
      are reluctant to invest large amounts of money in their teeth when they are
      already quite elderly and realize they may not live long enough to make the
      investment "worthwhile." Educating the patient regarding average life expectancy
      is sometimes helpful, but the experience of many clinical dentists is that many
      elderly persons either do not believe the numbers, require greater certainty in
      their "investments," or do not place as high a value on their dental health as
      they do other aspects of their lives (in a context in which there are more needs
      than resources to pay for them). Finally, many older adults, contrary to the
      popular bumper sticker, are trying to preserve as many resources for their
      children and grandchildren as possible. The final decision should be made with
      sensitivity to the overall needs of the patient, and with the assistance of a
      well-informed patient or other responsible party.

PMID- 1397435
TI  - Computerized design and manufacturing of esthetic dental restorations.
AB  - The "high-tech race" in restorative and esthetic dentistry is underway. The Cerec
      System, which currently leads the race, is reviewed. Other systems, which soon
      will be available, are discussed briefly. New and innovative technologies are
      sure to become a significant part of dentistry, both today and in the future.
      Many traditional methodologies and materials will be replaced by these new
      developments.

PMID- 1397436
TI  - Infection control in fixed prosthodontics.
AB  - The breadth and depth of our knowledge of infection control continues to increase
      in dramatic proportions. The literature is already massive and there is nothing
      to suggest an abatement of this situation. In truth, we can expect the very
      opposite; an escalation in attention at every level of concern, from the
      effectiveness of the chemical agents as actually used in the dental environment,
      to our methods of delivery, as well as the effects on the materials, equipment,
      and even the personnel in the dental setting. This trend undoubtedly will
      continue as our understanding of disease processes and the mechanisms of disease
      transmission increases. This will, in part, directly impact the scope and
      direction of future study of infection control practices in dentistry.

PMID- 1397437
TI  - Diagnostic considerations for the medically complex patient.
AB  - As advances in medical diagnostic and treatment modalities continue to increase
      the life expectancy of the population, the likelihood of encountering patients in
      dental practice with concomitant medical problems will also rise. Thus it will
      become increasingly important for practicing dentists to take thorough medical
      histories, recognize signs of systemic disorders, and work closely with their
      medical colleagues to ensure that safe dental care is rendered to these medically
      complex patients. Although acutely ill or severely compromised individuals may be
      best treated in a hospital setting by those with special training, all dental
      practitioners should possess the diagnostic and communicative skills needed to
      manage those who are receiving out-patient medical care.

PMID- 1397438
TI  - Candida and candidosis. Epidemiology, diagnosis and therapeutic management.
AB  - Infections caused by Candida species comprise one of the most common oral disease
      conditions encountered in the practice of dentistry. Gradual changes in
      population demographics have been accompanied by an increased incidence in
      candidal and related opportunistic infection rates. Candida albicans and other
      candidal species traditionally have been recognized as opportunistic pathogens.
      Recent advances in both the scientific basis for and the clinical significance of
      candidal organisms, however, have demonstrated these fungi to be distributed
      widely and to be important contributors to a broad range of mucosal and systemic
      disease conditions. These factors have allowed for a better understanding of
      fungal pathogenesis as it affects human oral disease through improvements in
      clinical and laboratory diagnosis and the therapeutic management of candidosis.

PMID- 1397439
TI  - Diagnosis and management of orofacial herpes simplex virus infections.
AB  - HSV disease remains a significant problem for the dental profession because of
      its widespread occurrence and ready transmission. Fortunately, available
      diagnostic techniques are highly sensitive and specific, antiviral therapy is
      effective in limiting the course of infection, and contemporary infection control
      procedures adequately safeguard dental personnel and the patient. Unfortunately,
      there is still a large segment of the population already infected with HSV-1 and
      the number of immunosuppressed latently infected patients continues to increase.
      Thus, patients will continue to need the help of the knowledgeable and willing
      dentist who can diagnose HSV-1 infection, provide effective treatment, and
      prevent transmission.

PMID- 1397440
TI  - Diagnosis and management of autoimmune and idiopathic mucosal diseases.
AB  - Several autoimmune and idiopathic diseases directly affect the oral mucosa.
      Current therapeutic management is aimed primarily at the control and prevention
      of symptoms. It is important for patients to understand the goals of therapeutic
      management because these diseases often are characterized by periods of remission
      and exacerbation that require long-term follow-up.

PMID- 1397441
TI  - Oral cancer. Etiology, recognition, and management.
AB  - The cure rate for oral cancers remains dismally low at approximately 50%. The
      dental profession is, to a large extent, responsible for decreasing the morbidity
      and mortality of oral cancer even though 50% of the population do not present for
      routine examination and care. The dental office team must accept the charge of
      educating all patients concerning the devastating role of tobacco and ethanol in
      promoting oral cancer, as well as malignancies at other sites. Dental clinicians
      play a vital role on the oral cancer team. Therefore, they must make themselves
      well aware of the diverse nature of oral cancer and must have an appropriate
      triage protocol in place so that lesions will be identified and managed correctly
      or referred promptly to the correct tertiary health care professionals. Early
      detection and prompt proper management can make a difference as we await the
      development of new and better ways of treating oral and oropharyngeal cancers.

PMID- 1397442
TI  - Diagnosis and management of acute and chronic oral complications of nonsurgical
      cancer therapies.
AB  - This article has reviewed selected oral complications that can develop in the
      myelosuppressed or head and neck radiation cancer patient. Many of these
      complications can be prevented by treating diseased oral sites prior to
      initiation of cancer therapy. Further, cancer treatment often causes changes in
      oral tissues that require long-term management. The dentist thus can play an
      important role in the overall care of many cancer patients.

PMID- 1397443
TI  - Recognition of worrisome facial conditions by the dentist.
AB  - We can see that there are a number of conditions that commonly occur on the skin
      of the face, and that these may be of little or great consequence to our
      patients. Dentists enjoy an ideal situation for the detection and management or
      referral of the more worrisome lesions. By paying close attention to the faces of
      dental patients, asking appropriate questions about the lesions discovered, and
      following up on the results of advise given to patients, dentists can play an
      important role as health care advisors concerning dermatologic conditions of the
      face.

PMID- 1397444
TI  - A clinical approach to the diagnosis of facial pain.
AB  - Following completion of the patient history, physical evaluation, and cranial
      nerve assessment, the next step should be a thorough dental evaluation with
      appropriate radiographs to evaluate caries, periodontal disease, and any other
      hard- or soft-tissue pathology. If indicated, a thorough evaluation of the
      craniomandibular complex also should be performed. At this point, the clinician
      should have a general idea as to the cause of the patient's facial pain and the
      appropriate course of treatment can then be instituted. If the problem is not
      solely dental in etiology, the diagnosis and management must be coordinated
      between the dentist and the appropriate medical specialties.

PMID- 1397445
TI  - Infection control for dental radiographic procedures in US dental hygiene
      programmes.
AB  - Infection control in dental radiographic procedures in US dental hygiene
      programmes has been investigated by means of a questionnaire and 76% (n = 148)
      responded. For intra-oral radiography, all but two programmes required the use of
      gloves during exposure procedures and 94% also required them during processing.
      Glasses, masks and other protective clothing were required less frequently than
      gloves. Equipment and working surfaces in the radiographic operatory were
      generally either disinfected or draped. Equipment and working surfaces in the
      darkroom were not usually afforded the same degree of diligence in disinfection.
      Most programmes dried film packets before processing and gave no special
      treatment to films after processing. Waste products were generally either tied
      off and marked as a biohazard or sterilized.

PMID- 1397446
TI  - Radiological characteristics of lead foils in dental film packets: analysis of
      components and shielding effect.
AB  - The radiological characteristics of the lead in five different dental film
      packets currently on the market in Japan were studied with monochromatic X-rays.
      Four packets were of a foil type while in the fifth, the lead was incorporated in
      the vinyl of the film packet. The samples were analysed by polychromatic photon
      absorptiometry, and the main component found to be lead with tin and/or antimony
      in smaller amounts. The shielding effect was calculated and, with the exception
      of the lead vinyl type, all found to exceed the ISO standard 3665. The lead foils
      attenuated the primary beam by, on average, 77% and 56% at 60 and 90 kVp
      respectively: in contrast, the reduction with the lead vinyl packet was only 38%
      and 23%. Using a 7 cm round beam, the lead foils reduced the dose by an average
      of 15% compared with 30% with a rectangular beam; the average dose reduction with
      the lead vinyl type was 8% and 15% respectively. These data show that the lead
      vinyl packet is unsuitable for clinical use and confirm the importance of optimum
      beam collimation for the reduction of patient risk.

PMID- 1397448
TI  - Radiographic selection criteria: the need for continued leadership.

PMID- 1397447
TI  - Measurements of tooth length in panoramic radiographs. 1. The use of indicators.
AB  - The aim of this study was to investigate both the actual and the radiographic
      tooth lengths of the maxillary first molar and second premolar and the mandibular
      premolars in panoramic radiographs. The actual length of 64 extracted teeth was
      measured. Steel balls were then attached to the cusp and apex and the teeth
      embedded in plastic moulds. Each pair of plaster casts with their set of teeth
      was radiographed with an Orthopantomograph twice at an interval of 1 month. The
      actual and the radiographic tooth length was measured twice by one observer. The
      mean tooth length of the molar was shorter than that of the premolars. The mean
      difference between the repeated measurements of the actual tooth length was small
      and ranged between 0.47 and 1.16% of the tooth length. The mean difference
      between repeated measurements of the radiographic tooth length was also small,
      with a method error of 0.13-0.21 mm. The vertical magnification in panoramic
      radiography was lower for mandibular premolars (13-15%) than for the maxillary
      second premolar and first molar (17-28%). The palatal root of the maxillary first
      molar had the highest vertical magnification (28%). Following the second set of
      radiographs, the mean difference between the measurements was small, except for
      the palatal root of the maxillary first molar (P < 0.001). Radiographic
      measurements of this root should therefore be used with caution. The results for
      the other roots examined indicate that these could be measured with high
      reproducibility.

PMID- 1397449
TI  - Measurements of tooth length in panoramic radiographs. 2: Observer performance.
AB  - Observer performance in tooth-length measurements in panoramic radiography has
      been examined. Sixty-four teeth, evenly distributed between maxillary first
      molars, second premolars and mandibular first and second premolars, were fixed in
      plastic moulds. Each cast was radiographed with an Orthopantomograph, twice with
      steel balls indicating the cusps and apices of the teeth and once without them.
      One observer measured the radiographic tooth length twice in both radiographs
      with indicators in order to estimate the true radiographic tooth length and the
      repositioning error, and twice in the radiographs without indicators. Seven other
      observers measured the tooth length on the radiographs without indicators, twice
      applying their own criteria and twice using defined criteria. The accuracy of the
      tooth-length measurements was calculated by comparing the true radiographic tooth
      length with the measurements of the seven observers. The intra-observer variation
      was defined as the difference between two measurements on the same radiograph.
      The accuracy and the precision of the tooth-length measurements were highly
      influenced by the observer performance. The mean radiographic tooth length of the
      seven observers was closer to the true radiographic tooth length when the
      observers applied the defined criteria. The inter- and intra-observer variation
      was higher for the measurements of the maxillary teeth (0.3-1.9 mm) compared with
      the mandibular teeth (0.3-0.9 mm) for most observers. The highest intra-observer
      variation was found for the palatal root of the maxillary first molar. The intra
      observer variation of four observers decreased somewhat when the defined criteria
      were used; for the other three observers, however, the variation
      increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397450
TI  - Radiological survey of the cervical spine in cleft lip and palate.
AB  - Cleft lip and palate is known to be associated with a number of other skeletal
      anomalies. The purpose of this study was to investigate the prevalence of
      possible malformations of the cervical spine and their relationship to
      velopharyngeal incompetence. The lateral cephalometric radiographs of 30 patients
      aged between 14 and 27 years of age with cleft lip and palate were compared with
      these of a control group, who had been involved in cycle accidents. The
      radiographs were assessed for morphological anomalies of the first and second
      cervical vertebrate and, in addition, longitudinal and angular measurements
      performed. Speech was assessed by electromagnetic articulography. A greater
      number of cervical spine anomalies were found in patients with cleft lip and
      palate and these were also associated with significantly (P < 0.05) greater
      osseous-nasopharyngeal depth.

PMID- 1397451
TI  - Comparison of photodensitometric with high-resolution digital analysis of bone
      density from serial dental radiographs.
AB  - Photodensitometry is known to provide high spatial resolution and continuous
      measurement of optical density for the analysis of dental radiographs, whereas
      digitization allows powerful image manipulations but, when using conventional
      video cameras, gives less spatial resolution and fewer grey levels. The aim of
      this study was therefore to develop a technique of high-resolution digital
      analysis for the measurement of bone density following the same principles as
      those of photodensitometry and based upon the use of a CCD Scanner Camera which
      provides up to 4096 grey levels and a spatial resolution of 4096 x 4096 pixels.
      Twenty-four zones were analysed with both techniques in five serial dental
      radiographs taken before and after periodontal therapy in eight patients.
      Statistical comparison of the results obtained by digital analysis and
      photodensitometry shows that the two techniques have the same accuracy.

PMID- 1397452
TI  - Rosette formation of impacted molar teeth in mucopolysaccharidoses and related
      disorders.
AB  - The radiographic features of the jaws in the mucopolysaccharidoses and related
      disorders (MPS) have been reviewed and three further cases are reported here,
      with particular reference to a novel dental anomaly, not previously described in
      detail, in two of them. The dental changes appear to be fully developed by the
      third decade and are characterized by bilateral multiple impacted molar teeth,
      which conglomerate in a single follicle to form a characteristic rosette of
      teeth. Rosetting was present only in relatively mature cases of MPS. However, it
      was also seen in the fourth patient, where we could not detect any other abnormal
      clinical or radiographic features. We therefore propose that since multiple
      rosetting of molar teeth can also occur in an isolated form, it is only
      suggestive of MPS.

PMID- 1397453
TI  - Effects of niobium filtration and constant potential on image quality in dental
      radiography. 2. Objective assessment.
AB  - The effects of niobium filtration and constant potential on image quality were
      explored by asking observers to identify numbers of circular areas of small
      density differences in zones of high and low density. Successful identification
      was related negatively to half-value layer. This relationship was particularly
      strong in the case of self-rectified units without additional niobium filtration
      and the constant potential units (r2 = 0.994, P < 0.0005). Constant potential had
      no effect other than in relation to half-value layer. Additional niobium
      filtration detracted from successful identification, but slightly less than would
      be predicted by the half-value layer. Whether this difference is significant or
      relevant has not been established. The findings of this study, in conjunction
      with our previous investigations, have failed to demonstrate any clear
      indications for preferring constant potential supply over self-rectification or
      for using niobium as an additional filter material. Half-value layer has been
      shown to be a reliable indicator of the effects of beam quality on emulsion
      speed, attenuation in water, and image quality. It appears that the methods
      employed to change the beam quality have no specific effects.

PMID- 1397454
TI  - Adenomatoid odontogenic tumour. Report of an unusual lesion in the posterior
      maxilla.
AB  - The adenomatoid odontogenic tumour most commonly presents as a 1.5-3 cm
      radiolucency in the anterior maxilla, and often associated with an unerupted
      tooth. It is very unusual for these tumours to occur behind the premolar region
      and the few reports of much bigger lesions have been in black African patients.
      This article describes an unusually large example of this tumour associated with
      an unerupted maxillary third molar tooth in a white female.

PMID- 1397455
TI  - Comprehensive oral X-ray diagnosis: Scanora multimodal radiography. A preliminary
      description.
AB  - Scanora (Soredex, Orion Corporation, Helsinki, Finland) is a multimodal
      radiography system which utilizes the principles of narrow beam radiography and
      spiral tomography. The system includes an integrated multifunction X-ray unit, a
      coordinate system for object localization and a wide selection of dental and
      maxillofacial imaging problems. All imaging procedures are computer controlled
      and executed automatically. Clinical experience and preliminary results show that
      the multimodal imaging system has great potential in the detection of
      pathological conditions of the maxillofacial region.

PMID- 1397456
TI  - The value of magnetic resonance imaging in the assessment of a sublingual
      epidermoid cyst.
AB  - A case is presented demonstrating the value of magnetic resonance imaging (MRI)
      in the assessment of a midline sublingual epidermoid cyst in a 22-year-old
      female. The advantages of MRI compared with CT in the evaluation of soft-tissue
      lesions in the sublingual space are discussed.

PMID- 1397458
TI  - Absorbed doses and energy imparted from tomography for dental implant
      installation. Spiral tomography using the Scanora technique compared with
      hypocycloidal tomography.
AB  - Tomography is sometimes needed to obtain information on the amount of bone
      available in the maxilla and in the posterior parts of the mandible prior to
      implant surgery. Both conventional and computed tomography can be employed.
      Recently a new imaging device, the Scanora, has been introduced which can be used
      for spiral tomography. The aim of this study was to compare absorbed doses and
      energy imparted from this new unit with those from conventional hypocycloidal
      tomography using the Philips Universal Polytome. A multi-film cassette with five
      pairs of calcium tungstate screens was used in the latter while a single film
      technique was used with the Scanora. The absorbed dose measurements were made on
      an anthropomorphic phantom. Most absorbed doses were found to be below 0.2 mGy
      except those to the major salivary glands. The absorbed doses with the Scanora
      were higher than with the Polytome. The beam direction and shorter focus-object
      distance in the Scanora influenced the absorbed dose distribution. The energy
      imparted was found to be low for both techniques, 1.8-1.9 mJ with the Scanora for
      both jaws, and for hypocycloidal tomography 0.78 mJ in the maxilla and 1.3 mJ in
      the mandible.

PMID- 1397457
TI  - Digital subtraction radiography in artificial recurrent caries detection.
AB  - The diagnostic accuracy of digital subtraction radiography in detection of
      artificial recurrent caries lesions was assessed in this project. The use of
      digital subtraction radiography has been shown to markedly increase the accuracy
      of the detection of destruction in the periodontal bone, but the method has not
      been evaluated in secondary caries detection. Defects of three different sizes,
      simulating recurrent caries, were sequentially prepared in the interproximal
      cavity preparation margins of 28 teeth. Two composite restorative materials with
      different radiographic densities were used as posterior restorations, and a
      radiograph was obtained of each defect size and restorative material. The
      radiographs were digitized and subtracted from the reference images, and the
      conventional radiographs and the subtraction images were evaluated by seven
      observers. The data were analysed with ROC statistics. Subtraction radiography
      was found to be superior to conventional radiography in recurrent caries
      detection, mainly by reducing the false-positive diagnoses. The radiopacity of
      the restorative material had a significant effect on accuracy with conventional
      but not with subtraction radiography.

PMID- 1397459
TI  - Orbital volume measured by a low-dose CT scanning technique.
AB  - A method for measuring orbital volume using low-dose CT with contiguous 3 mm
      transaxial sections is described. The accuracy of the method is 1.6%, as
      demonstrated by comparing CT volume measurements with those derived directly from
      alginate impressions and on repeat scanning the precision of the measurement was
      judged as 1.3%. Within the same individual, the right and left orbital volumes
      were observed to be within 0.6 cm3 (s.d. +/- 0.33 cm3) of each other. This study
      demonstrates that low-dose CT scanning is a practical method of determining
      orbital volume and could be used to advantage in the management of traumatic
      enophthalmos and blow-out fractures of the orbit.

PMID- 1397460
TI  - Effects of additional filtration on image quality in dental radiography:
      comparison of niobium with aluminium.
AB  - Niobium filtration was compared with additional aluminium filtration with respect
      to the image quality of dental radiographs. An aluminium phantom was constructed
      which produced densities similar to those found in periapical regions and in
      enamel. Eight beam qualities were investigated and objective evaluation of the
      films was made by 20 observers with respect to any effects on radiographic
      contrast and successful identification of a pattern of holes in the phantom.
      Radiographic contrast decreased linearly as the half-value layer increased (r2 =
      0.960, P < 0.0005), confirming the negative relationship between contrast and
      half-value layer as previously shown. No specific effect of niobium filtration on
      radiographic contrast was demonstrated. The number of successful identifications
      decreased with increasing half-value layer. A regression analysis in the total
      and dark zones yielded r2 values of 0.937 and 0.943 (P < 0.0005). Similar
      analyses for both the light and overall zones showed weaker relationships (r2 =
      0.734 and 0.742: P = 0.007 and 0.006 respectively). Niobium reduces successful
      identification to the same extent as equivalent aluminium filtration.

PMID- 1397461
TI  - The contribution of frontal tomography to the diagnosis of temporomandibular
      joint osteoarthritis.
AB  - The contribution of frontal tomography to the diagnosis of temporomandibular
      joint (TMJ) osteoarthritis has been investigated. Ninety-one patients with
      clinically defined TMJ disorders were examined by simultaneous lateral and
      frontal TMJ tomograms taken in the intercuspal position. Abnormal findings were
      observed on frontal tomograms in 31 joints and suspicious findings in 22 joints.
      On the other hand, there were 41 joints with abnormal findings and 22 joints with
      suspicious findings on the lateral tomograms. Suspicious or abnormal findings
      were found on frontal tomograms alone in 14 joints (7.7%) of 14 patients (15.4%).
      It is concluded that simultaneous lateral and frontal tomography produces a more
      accurate radiographic diagnosis of TMJ osteoarthritis.

PMID- 1397462
TI  - Accuracy of quantification of mandibular condyle displacement in digitally
      subtracted linear tomograms.
AB  - Using a TMJ skeletal phantom, we assessed validity and reliability of digitally
      subtracted linear tomographic images to quantify condylar position changes.
      Horizontally corrected frontal and lateral tomographic images were made with the
      condyle in a 'centred' position and displaced by 1, 2 and 3 mm increments in two
      of three directions (inferior, and posterior, or lateral). Film images were
      sequentially subtracted and then randomized so that observers were blinded to the
      amount and direction of condylar movement. Averages of three measurements of the
      dark bands representing condylar shifts were made using a digitizing tablet. The
      study utilized a nested design where the series of film images was subtracted
      twice and each subtraction was read twice by two examiners. We repeated the study
      with a second series of films treated in an identical manner. Average differences
      from expected values were similar for frontal and lateral techniques and all
      directions and increments of displacement. Typical average difference for any
      increment was less than 0.1 mm. Standard deviations in measures were similar
      across techniques and increments and were typically less than 0.1 mm. Significant
      variation in the absolute value of differences between measured and expected
      values by direction of condylar displacement was attributed to greater accuracy
      of registration on the vertical axis for frontal images. A significant source of
      variation in the study design element 'film set' was attributed to errors in
      repositioning the phantom.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397463
TI  - Standardized lateral oblique projection of the mandible for digital subtraction
      radiography.
AB  - A special apparatus was developed for standardization of the lateral oblique
      projection of the mandible (LOPM) in order to apply the digital subtraction
      method. Geometric reproducibility was examined over an 8-week period using a dry
      skull. Angulation errors were determined by the relation to image noise in the
      subtraction image. It was found that the relation between image noise and
      angulation error was approximated by a second-order polynomial. Geometric
      reproducibility was within 1 degree over the experimental period. These results
      suggest that this standardized LOPM is satisfactory for clinical application of
      digital subtraction. Two cases are presented where this technique was used to
      demonstrate longitudinal changes in bone density.

PMID- 1397464
TI  - Localization of a displaced root fragment by stereoscopy and pluridirecitonal
      tomography.
AB  - The case reported describes two methods used with the Scanora integrated imaging
      system to locate a root fragment thought to be displaced into the maxillary sinus
      -rotational narrow beam stereoscopic scanning and wide angle cross-sectional
      pluridirectional tomography. While the stereo scans located the fragment within
      the sinus, a more accurate determination of its site, in relation to an object of
      known position, was obtained from the tomograms.

PMID- 1397465
TI  - Achieving efficacy in oral radiology--out of the woods, and into decision trees?

PMID- 1397466
TI  - 1992 assessment of radiation risk from dental radiography.
AB  - Recent studies suggest that the lifetime cancer risks from exposure to low levels
      of ionizing radiation may be greater than previously estimated. This review first
      summarizes the findings of these studies as they pertain to dental radiology,
      then uses their concepts in combination with dosimetry from the dental literature
      to estimate the radiation risk from dental radiology. Estimation of risk from
      groups of exposed individuals requires use of mathematical models that fit the
      epidemiological data. The ICRP estimates that a single brief whole-body exposure
      of 1 Gy to 10,000 people results in about 500 additional cancer deaths over the
      lifetime of the exposed individuals, assuming a dose rate effectiveness factor of
      2 for cancers other than leukaemia. Leukaemias are seen as a wave from 5 to 30
      years following exposure. Cancers other than leukaemia typically start to appear
      about 10 years following exposure and remain in excess for as long as most
      exposed populations are followed, presumably for the lifetime of the exposed
      individuals. The gonadal dose is so small from dental radiography that the risk
      of heritable defects is negligible in comparison with the somatic risk. The
      dental literature contains several studies reporting sufficient dosimetric data
      for radiosensitive sites in the head and neck to allow estimation of the risk of
      fatal cancers from intra-oral and panoramic radiography. The highest estimated
      risks (using the ICRP data) are for leukaemia (bone marrow), thyroid and bone
      surface cancer. The total risk is estimated to be 2.5 fatal malignancies per
      10(6) full-mouth examinations made with D-speed film and round
      collimation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397467
TI  - A comparison of conventional intra-oral radiography and computer imaging
      techniques for the detection of proximal surface dental caries.
AB  - The detection of proximal surface caries by the visual interpretation of bitewing
      radiographs is known to be relatively inaccurate. The present study was designed
      to examine whether computer image processing could improve the diagnostic
      accuracy. A computer-aided, software-driven, TV-based system was used to digitize
      conventional radiographs and digitally process the images using histogram
      equalization and grey-scale inversion to enhance the images. The computer
      enhanced images were compared with conventional intra-oral radiographs for the
      detection of proximal surface caries using receiver operating characteristic
      analysis. The results indicate that the digital image processing techniques used
      did not improve the diagnostic accuracy of dental radiographs. No significant
      difference in diagnostic accuracy could be detected between the non-enhanced
      digital images and conventional film-based images for the detection of proximal
      surface caries.

PMID- 1397468
TI  - Individualized periapical radiography determined by clinical and panoramic
      examination.
AB  - The efficiency of panoramic radiography compared with full-mouth periapical
      examination is an unresolved problem. The diagnostic yield of periapical lesions
      when the clinical signs and symptoms and the findings from a panoramic radiograph
      served as the basis for an individualized periapical radiographic examination was
      studied. Two hundred patients were examined clinically and radiographically. The
      periapical status was assessed step by step with access to increasing numbers of
      radiographs. For the clinical examination, the sensitivity was 0.24, the positive
      predictive value 0.62, the specificity 0.98, the negative predictive value 0.90
      and the likelihood ratio for the positive test result 12. For radiographs
      indicated by the clinical examination plus the panoramic radiograph and selected
      periapical radiographs, both the sensitivity and the positive predictive value
      were 0.91, the specificity and the negative predictive value 0.99 each and the
      likelihood ratio was 91. False findings were twice as frequent in the upper as in
      the lower arch and particularly found in the incisor and premolar regions. In 30%
      of the patients no periapical radiograph was needed to supplement the panoramic
      radiograph. In the other patients, two supplementary periapical radiographs were
      needed on average. We conclude that the information obtained from the clinical
      and panoramic examinations supplemented with no more than two periapical
      radiographs will result in a high diagnostic yield on the periapical status.

PMID- 1397469
TI  - Recognizing invariant geometric structure in dental radiographs.
AB  - The dental radiograph is a non-invasive tool that is used to view internal
      structures for the diagnosis of caries, periapical lesions and periodontal
      disease. The requirement for a standardized image is most prominent in
      periodontal disease since the diagnosis is best done with a difference
      radiograph. The difficulty is that exact registration for subtraction requires
      exact reproduction of imaging geometry. A new model of imaging geometry, based on
      the correspondence of 3D structures, to describe the radiograph formation process
      is presented. The experimental results show that 3D measurements can be made in
      dental radiographs (P < 0.01) with up to 16-mm translation errors and angulation
      errors of up to 32 degrees.

PMID- 1397470
TI  - Three-dimensional reconstruction of magnetic resonance images of the
      temporomandibular joint by I-DEAS.
AB  - Evaluation of the temporomandibular joint has been limited by the inability of
      current technology to image complex morphology and motion in three dimensions. An
      engineering design program, I-DEAS, has been used to construct solid models from
      magnetic resonance images. A dried skull with an acrylic resin temporomandibular
      disc replica, immersed in water, provided sagittal and coronal MR images. Linear
      dimensions and disc volumes obtained from the models were compared with the
      original and found to be consistent, within the limits imposed by the slice
      thickness. We have applied the method to the living joint in an asymptomatic
      volunteer, and report our initial experience in demonstrating the spatial
      relationships and motion of the joint components.

PMID- 1397471
TI  - Cost-effectiveness decision analysis of obtaining periapical radiographs of
      traumatized maxillary incisors.
AB  - A long-term decision analysis approach has been applied to the problem of whether
      or not periapical radiographs should be taken routinely of patients presenting
      with simple fractures of otherwise asymptomatic maxillary incisors. Information
      from the literature concerning the accuracy of cold, hot and electrical tests for
      pulp vitality, combined with data on the accuracy of radiographic diagnosis of
      periapical pathology, and therefore vitality, has been used in the analysis of
      the diagnostic problem structured in the form of a decision tree. By adding
      information concerning the direct costs of examining and treating patients over a
      10-year period to the analysis and varying the likely prevalence of periapical
      lesions in a three-way sensitivity analysis, the following results were arrived
      at: (1) if the disease prevalence in teenage patients is < 5%, it is economically
      justifiable to make a visual inspection only and then to proceed with simple
      restorative treatment; (2) if there is evidence from the clinical examination or
      patient history that the prevalence of pulp necrosis is between 5% and 50% then,
      in our case, radiographs were the most appropriate single diagnostic test.

PMID- 1397472
TI  - Digital dental image processing of alveolar bone: Macintosh II personal computer
      software.
AB  - Dental radiographs are amenable to digital image processing and analysis for both
      subjective interpretation and quantification of scene features. Four general
      purpose image processing programs for the Apple Macintosh II computer (NIH Image,
      Enhance, IP Lab and DIP Station) were applied to digital analysis of dental
      radiographs. These programs can manipulate and quantitatively analyse the gray
      scale and spatial data of dental images and improve their subjective quality.
      They can interactively make geometric measurements of features. The programs were
      evaluated for their versatility and applicability in the quantification of
      alveolar bone. Overall, NIH Image was judged most suitable for current dental
      imaging needs. Each of the other programs offered unique features that may be
      valuable in specific applications.

PMID- 1397473
TI  - Impaired immune responses in diabetes mellitus: analysis of the factors and
      mechanisms involved. Relevance to the increased susceptibility of diabetic
      patients to specific infections.
AB  - The reasons why diabetic patients present with an increased susceptibility to
      frequent and protracted infections remain unclear. The virtual absence of
      epidemiological studies of the independent risk factors involved contrasts with
      the multitude of in vitro models focused on the metabolism and function of immune
      cells from diabetic patients. This review analyzes some of these models and their
      clinical relevance. The different levels of diabetes pathogenesis: genetic (Type
      1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for
      immune abnormalities demonstrated in in vitro models. The participation of
      genetic and autoimmune factors has been mainly characterized on T lymphocyte
      function. The B8 DR3 haplotype is associated with several minor immunologic
      abnormalities in vitro. However, the high frequency of this haplotype in healthy
      individuals argues against its involvement in significant defects of
      antimicrobial immunity. Genetic deficiency of C4, present in 25% of Type 1
      diabetic patients could, on the other hand, be responsible for opsonization
      defects against encapsulated pathogens. Several immunological abnormalities
      related to the autoimmune process preceding the onset of Type 1 diabetes
      mellitus, such as the depletion of memory CD4+ cells and the defective natural
      killer activity could transiently impair host defences against viral diseases.
      Several in vitro functional defects of the immune system have been correlated
      with the metabolic control of diabetic patients. This suggests the involvement of
      insulinopenia in some of the abnormalities observed. Insulinopenia-induced
      enzymatic defects have often been proposed to inhibit energy-requiring functions
      of phagocytes and lymphocytes. However, the relevance of this mechanism could be
      confined to patients with extremely severe metabolic abnormalities. The
      importance of systemic consequences of insulinopenia such as hyperglycaemia and
      ketosis has also been addressed. Usually, the defects induced in vitro by these
      factors are slight and require supraphysiologic concentrations of glucose or
      ketone bodies. Recent studies have shown abnormalities of signal transduction
      mechanisms in which insulinopenia itself and other factors such as circulating
      immune complexes could be involved. Despite numerous controversies, many in vitro
      studies of the immune cells of diabetic patients have demonstrated significant
      defects which bear quantitative similarities with abnormalities described in
      other immunodeficiency syndromes. Furthermore, several mechanisms have been
      proposed to link the different defects observed with the specific infections
      encountered in diabetic patients.

PMID- 1397474
TI  - Role of prostaglandin E2 (PGE2) in the growth hormone releasing hormone action on
      growth hormone, insulin and C-peptide in normal men.
AB  - Fourteen healthy men were placed in two treatment groups. 1. Seven men received
      growth releasing hormone (1 microgram/kg BW) intravenously during either saline
      or prostaglandin E2 (10 micrograms/min) infusion which were started 60 minutes
      before testing. Growth hormone response to growth releasing hormone was greater
      during prostaglandin E2 infusion compared to the control study. These data
      suggest that exogenous prostaglandin E2 positively modulates growth hormone
      response to growth releasing hormone. In the second group consisting also of 7
      men a GRH test was performed before and after 3 days administration of
      meclofenamate. Meclofenamate significantly reduced plasma levels of stable
      metabolites of prostaglandin E2 as well as the growth hormone to growth releasing
      hormone, suggesting that the GRH effect on GH was at least partly under
      prostaglandin E2 control. GRH significantly reduced serum insulin in the two
      treatment groups. PGE2 infusion or meclofenamate did not change insulin response
      to GRH. Serum C-peptide and blood glucose did not change after GRH injection
      during saline or PGE2 infusions.

PMID- 1397475
TI  - Increased muscular phospholipase A2 activity in diabetic rats.
AB  - Anomalies in prostaglandin (PG) synthesis have been suggested in both
      experimental and human diabetes mellitus; increased levels of plasma and tissue
      eicosanoids has been recently reported by several investigators. One step in
      prostaglandin synthesis is the enzymatic hydrolysis of membrane phospholipids by
      Phospholipase A2 (PLA2). Nevertheless the alternative pathway involving
      Phospholipase C must be considered. An evaluation of PLA2 activity is therefore a
      useful method for studying prostaglandin synthesis in the peripheral target
      tissues of insulin activity. We studied PLA2 activity in normal and diabetic rat
      muscle. Streptozotocin-induced diabetic rats showed significantly higher muscular
      PLA2 activity when compared with controls (3.04 x 10(-2) +/- 0.50 x 10(-2) versus
      1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1 (p less
      than 0.01). This effect was not observed in diabetic animals successfully treated
      with insulin (1.78 x 10(-2) +/- 0.5 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(
      2) arachidonic acid pMol.mg protein-1.min-1), and a significant correlation was
      found between blood glucose and muscular PLA2 activity (r = 0.42; p less than
      0.05). Our results clearly show that in streptozotocin-induced diabetic rats
      muscular PLA2 activity is significantly higher. The relationship between blood
      glucose levels and muscular PLA2 activity and the decrease of PLA2 activity after
      insulin treatment suggest that these changes may be related to a defect in
      insulin effect.

PMID- 1397476
TI  - Neuropathy target esterase is not reduced in neural tissues of diabetic rats.
AB  - Marked (greater than 70%) reduction of the neuropathy target enzyme (NTE) shortly
      after exposure to organophosphorus compounds heralds the onset of delayed
      neuropathic damage in animals and humans. One previous study reported that
      lymphocyte NTE from diabetic patients was depressed by greater than 70%; such a
      reduction was considered to be a biological marker of diabetic polyneuropathy. To
      ascertain whether NTE from target tissues might be involved in diabetic
      neuropathy, we measured NTE activity in the brain, spinal cord and peripheral
      nerves of streptozotocin-diabetic rats. No reduction in NTE activity was detected
      in these neural specimens. Therefore, it is concluded that NTE is not involved in
      diabetic nerve damage and that the meaning of low NTE activity in peripheral
      lymphocytes of diabetic patients remains unclear.

PMID- 1397477
TI  - Comparison of the effects of bezafibrate and acipimox on the lipid pattern and
      plasma fibrinogen in hyperlipidaemic type 2 (non-insulin-dependent) diabetic
      patients.
AB  - Correction of cardiovascular risk factors is of particular significance in a high
      risk population, such as that of diabetic patients. This paper reports the
      effects of one-month administration of 400 mg/day Bezafibrate (BZF), followed by
      a two-month wash-out and one-month administration of 500 mg/day Acipimox (APX) or
      vice versa in a random order in 16 Type 2 diabetic patients with diet-resistant
      hyperlipidaemia and in good metabolic control (HbA1c less than 8%), on plasma
      fibrinogen and on their lipid pattern. Metabolic control displayed a
      nonsignificant improvement (HbA1c) during both treatments (stable body weight).
      Both BZF and APX produced a 14% decrease in total CHOL (p less than 0.01),
      whereas BZF was more effective in reducing triglycerides (tg) (-37% vs -15%). The
      marked BZF-induced Tg reduction was associated with a proportional decrease in
      Apo B, while an increase in total HDL-, HDL2 and HDL3-CHOL, together with a
      significant increase in Apo AI, was observed. APX treatment resulted in a HDL2
      CHOL increase only (+29%). Both drugs reduced VLDL-CHOL (BZF -37%; APX -15%) and
      VLDL-Tg (-56% and -34%). In BZF treated patients Apo CIII fell indicating a
      possible reduction of specific inhibition of lipoprotein lipase activity, while
      APX affected both Apo CII (+23%) and Apo CIII (-26%) and led to a 62% Apo
      CII/CIII ratio increase. BZF alone led to a significant 25% decrease in plasma
      fibrinogen (from 415 +/- 14.3 to 312.1 +/- 18.1 SEM mg/dl, p less than
      0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397479
TI  - [The role of lipoprotein(a) dose in diabetes mellitus].

PMID- 1397478
TI  - [Known diabetes mellitus in Algeria: frequency and sequelae].
AB  - A sampling survey was carried out in Algiers in order to assess the frequency of
      the previously known diabetes mellitus and to appraise the handicap resulting
      from this disease. This study was undertaken among 1,302 households, i.e., 9,384
      inhabitants. A questionnaire was used to identify people with diabetes. The
      overall prevalence of diabetes was 21.7 per thousand inhabitants while the annual
      incidence was estimated as 2.0 per thousand. 18.1% of previously known diabetics
      were insulin-treated. Diabetes became strikingly more prevalent with advancing
      age, being over 140 per thousand among women after 60 years. There was no
      significant difference in the prevalence rates of diabetes among the different
      social levels. Diabetes was scarcely revealed by a systematic examination (20%).
      More than one third of the diabetic patients were without any handicap. The most
      serious handicaps were notably observed among old people. Significant differences
      between the mean ridits of handicap were observed only when people over 60 were
      compared to the other age groups for physical independence, mobility and
      occupation.

PMID- 1397480
TI  - Iodothyronine 5'-deiodinating activity in the pineal gland.
AB  - 1. The presence of an iodothyronine 5'-deiodinating activity has been described
      in the pineal gland of various rodents, and it has been identified as a type II
      5'-deiodinase isoenzyme since it is relatively insensitive to inhibition by
      propylthiouracil and its activity increases during hypothyroidism. 2. 5'
      Deiodinase activity in the rat pineal gland follows a nyctohemeral profile,
      exhibiting basal values during the day and maximal values at night. The nocturnal
      increase is dependent on the noradrenergic input from the superior cervical
      ganglia, and both in vivo and in vitro studies show that beta-adrenergic
      receptors are primarily involved in the activation of the enzyme. 3. Day-night
      differences in rat pineal 5'-deiodinase activity are found beginning at 2 weeks
      of age, with rhythms increasing in amplitude until maximal differences are
      reached in adult animals. During the maturation of the rhythm, changes in
      regulation of enzyme activation are observed. Thus, during the first 2-3 weeks of
      age, alpha-adrenergic receptors appear to be as important as beta-adrenergic
      receptors in regulating the deiodinating activity of the pineal. However, in
      adults, no role of alpha-adrenergic receptors has been described. 4. Although
      regulation of 5'-deiodinase activity in the pineal gland is well established, few
      data are available concerning the physiological significance of the enzyme in the
      gland. Of the studies that have been performed, those attempting to demonstrate a
      relationship between pineal 5'-deiodinase activity and other pineal rhythms, e.g.
      those of melatonin production and N-acetyltransferase activity, indicates that
      the latter rhythms do not rely on the cyclic production of T3. The alternate
      possibility that the 5'D rhythm depends on the cyclic production of melatonin
      remains to be examined.

PMID- 1397481
TI  - 31P NMR of Mg-ATP in dilute solutions: complexation and exchange.
AB  - 1. Monovalent-cation [(CH3)4N+, K(I), Na(I)] ATP, 1 mM in nucleotide, in aqueous
      solutions at pH 7.2, 24 degrees C, generates 2 different 31P NMR spectra,
      depending upon the salt content of the solution. At salt concentrations below 10
      mM, the 31P NMR signals are chemically-shifted upfield (Na salt: alpha, -11.44
      delta; beta, -22.91 delta; gamma, -8.36 delta) and the beta- and gamma-groups are
      broadened (at half-height: alpha, 3.5 Hz; beta, 9.6 Hz; gamma, 69 Hz). Above 10
      mM salt, the signals are shifted downfield and are narrow (Na salt: alpha, -11.09
      delta, 1.9 Hz; beta, -21.75 delta, 3.3 Hz; gamma, -6.30 delta, 3.9 Hz). 2. The Na
      Mg-ATP complex, corresponding to the composition Na6Mg1ATP2, yields a single set
      of 31P resonances at concentrations of nucleotide of 100 mM, that upon dilution
      to 0.2 mM, resolve into 2 sets of ATP resonances characterized by low-field and
      high-field beta- and gamma-group resonance pairs. This set of ATP resonances, in
      contrast to the resonance set at 100 mM ATP, are broad (100 mM in ATP: alpha, 
      10.7 delta, 3.7 Hz; beta, -20.1 delta, 15 Hz; gamma, -5.7 delta, 7.3 Hz. 0.2 mM
      in ATP: alpha, -10.7 delta, 47 Hz; beta, -18.8 and -21.6 delta, 316 and 274 Hz;
      gamma, -5.5 and -8.7 delta, 460 and 374 Hz). 3. This new data, in combination
      with data derived from a survey of metal-ion-ATP studies, are interpreted in
      terms of ATP dimers, incorporating 2 molecules of ATP and 2 metal cations, that
      exist in water under the physiological conditions of neutral pH, high salt
      content [135 mM K(I)] and ATP concentrations in the range of 3 mM. 4. A
      compilation of 31P in vivo and ex vivo data compared to a reference Mg-ATP
      chemical shift vs Mg/ATP ratio plot indicates that ATP is not fully Mg-saturated
      in living systems and that 41% exists as the Mg(ATP)2 complex.

PMID- 1397482
TI  - Purification of lysosomal arylsulfatase B from rat liver and its reactivity with
      lectins in affinity immunoelectrophoresis.
AB  - 1. Arylsulfatase B (ASB) from lysosomal fraction of rat liver were isolated and
      purified 260-fold with a recovery of about 5%. 2. The enzyme in gradient PAGE 4
      30% followed by immunoelectrophoresis migrated as a single peak of M(r) 84,000.
      The pI, measured by isoelectrofocusing in agarose followed by
      immunoelectrophoresis, was equal to 6.7. 3. ASB reacted with Con A, LCA, PSA,
      LTL, WGA, RCAI and did not react with PHA, SBA, HPA, CAA and PAL in crossed
      affino-immunoelectrophoresis or rocket immunoelectrophoresis. These results
      permit of preliminary elucidation of ASB glycan structure.

PMID- 1397483
TI  - Isolation and characterization of bovine gingival proteoglycans versican and
      decorin.
AB  - 1. We have isolated, chemically and immunologically characterized versican and
      decorin from bovine gingiva. 2. Versican was of large molecular weight and the
      molecular size of the core protein was estimated to be greater than 200 kDa. 3.
      The glycosaminoglycan chains were susceptible to chondroitinase ABC and N-linked
      oligosaccharides were present on the protein core of the molecule. 4.
      Immunological studies provided evidence that a hyaluronic acid binding region was
      present in the core protein of versican. 5. The overall structure was similar to
      that of versican isolated from bovine sclera. 6. Decorin had a molecular weight
      of 102 kDa and its glycosaminoglycan chain was completely digested by specific
      glycosidases. 7. The partially deglycosylated core protein had a molecular weight
      of 55 kDa and N-linked oligosaccharides were present on the molecule.

PMID- 1397484
TI  - Use of an immobilized human endogenous lectin for the purification of
      complementary ligands.
AB  - 1. A galactoside-specific endogenous lectin isolated from human brain was
      covalently immobilized on divinylsulfone-activated agarose. This highly selective
      affinity adsorbent proved to be useful in purifying soluble protein ligands. 2.
      The maximum binding capacity of the adsorbent for complementary proteins was
      calculated to be 618 micrograms per g of gel (wet resin). 3. Sequential elutions
      using 0.1 M lactose, 0.3 M lactose and 0.5 M NaCl, and competition assays using
      incorporation in the presence 0.1 M lactose revealed differences in lectin-ligand
      interactions.

PMID- 1397485
TI  - Metabolism of very low density lipoproteins in the pig. An in vivo study.
AB  - 1. The metabolism of apolipoprotein B (apoB) was investigated in pigs injected
      with [125I]very low density lipoproteins (VLDL) to determine to which extent the
      two distinct low density lipoprotein subclasses (LDL1 and LDL2) derive from VLDL.
      2. The lipoproteins were isolated by density gradient ultracentrifugation and the
      transfer of radioactivity from VLDL into LDL1 and LDL2 apoB was measured. 3. Only
      a minor portion of VLDL apoB was converted to LDL1 (7.7 +/- 3.2%) and LDL2 (3.6
      +/- 1.5%), respectively. Thus, we conclude that the major portion of LDL,
      especially LDL2, is synthesized independently from VLDL catabolism.

PMID- 1397486
TI  - Pregnancy modulates the expression of beta-N-acetylhexosaminidase in rat serum
      and tissues.
AB  - 1. beta-N-Acetylhexosaminidases in maternal rat serum were separated by DEAE
      cellulose chromatography and compared with those of adult rat serum. 2. In
      pregnant serum there is an increase of the isoenzymes which are entirely composed
      of beta-subunits (B and intermediate forms). 3. These alterations could be
      compared to those already described in human pregnancy. 4. The levels of beta-N
      acetylhexosaminidase and the relative expression of alpha- and beta-subunits in
      normal and pregnant serum correlate with the above isoenzyme expression. 5. The
      increase of B and intermediate forms as well as the increase of specific activity
      during pregnancy was not peculiar to maternal serum but was also demonstrated in
      several foetal tissues and in maternal tissues, in which cases the beta-N
      acetylhexosaminidase isoenzyme patterns closely resemble the foetal ones rather
      than those of the adult rat tissues. 6. These analogies strongly suggest that the
      expression of beta-subunit of beta-N-acetylhexosaminidase is regulated by
      hormones or other factors related to pregnancy.

PMID- 1397487
TI  - Lipoxygenase activity in the brain regions of young chicks: isolation and some
      properties.
AB  - 1. The lipoxygenase (LOX) oxygenation pathway of arachidonic acid was
      investigated in the cerebellum and cerebral hemispheres of young chicks. 2.
      Lipoxygenase products consisted mainly of 15-hydroxyeicosatetraenoic acid (15
      HETE), accompanied by the 15-hydroperoxy analog (15-HPETE) and the 5-HETE
      product. 3. The yield of 15-HETE was 3 times greater in the cerebellar system
      than in the cerebrum. 4. PLA2 activity of the cerebellum was twice that of the
      cerebrum. 5. Affinity chromatography revealed 2 brain fractions with LOX activity
      which were assayed with either linoleic or arachidonic acid as substrate. 6. The
      fraction eluted with 0.2 M sodium acetate pH 5.0, produced a higher yield and
      enrichment of LOX activity than the eluate obtained with 0.1 M Tris-HCl buffer
      (pH 8.0). 7. A considerably higher yield and enrichment of the enzyme was
      achieved when the starting material was the cerebellum, compared to the cerebrum.
      8. The optimal pH for both purified fractions from cerebrum and cerebellum was
      6.5, with either linoleic or arachidonic acid as substrate. 9. The cerebral LOX
      yielded Michaelis-Menten kinetics when linoleic acid was the substrate, while the
      corresponding plots for the cerebellar enzyme were sigmoidal. 10. Arachidonic
      acid as substrate produced sigmoidal plots, except at pH 5.0, where Michaelis
      Menten kinetics were observed. 11. These results and the elevated activities of
      PLA2 and 15-LOX could be significant in relation to the special vulnerability of
      the cerebellum in chick nutritional encephalomalacia.

PMID- 1397488
TI  - Inhibition by aluminum ion of NAD- and NADP-dependent isocitrate dehydrogenases
      from yeast.
AB  - 1. NADP-dependent isocitrate dehydrogenase from yeast was potently inhibited by
      aluminum ion competitively with respect to the substrate isocitrate, and
      noncompetitively with the other substrate NADP. Ki value was determined to be
      0.43 microM. 2. Aluminum ion acted as only a weak allosteric inhibitor of yeast
      NAD-dependent isocitrate dehydrogenase toward isocitrate, and as a noncompetitive
      inhibitor toward NAD. 3. Inhibition by aluminum ion of NADP- and NAD-isocitrate
      dehydrogenases can reduce the aerobic energy production in yeast, and may
      contribute to the biological toxicity of aluminum in ecosystems and human life.

PMID- 1397489
TI  - Acid phosphatases in mammalian tissues. Evidence for the existence of a 57 kDa
      Zn(2+)-dependent acid phosphatase form.
AB  - 1. A comparative study of multiple forms of acid phosphatase (AcPase) in various
      organs of mammals was carried out. 2. These studies indicated that the high
      molecular weight AcPase is preferentially expressed by tissues which undergo cell
      proliferation such as epithelial tissues; on the contrary, the low-molecular
      weight enzyme seems to be characteristic of highly differentiated tissues such as
      nervous, muscle and blood erythrocytes. 3. The existence of a new AcPase
      activated by Zn2+ ions was observed in all tissues studied with the exception of
      erythrocytes. 4. The enzyme shows a molecular weight of 57 kDa, is insensitive to
      NaF, hydrolyzes p-nitro-phenylphosphate and o-c-phenylphosphate; ATP, a-naphthyl
      phosphate and beta-glycerolphosphate are also dephosphorylated.

PMID- 1397490
TI  - Modulation of ribonuclease P expression in Escherichia coli by polyamines.
AB  - 1. The presence of polyamines in the growth medium of Escherichia coli can
      modulate the activity of the RNA-processing enzyme, ribonucleoprotein
      ribonuclease P (RNase P), by altering the expression of the rnpA and rnpB genes,
      which encode its C5 protein and M1 RNA subunits, respectively. 2. Following
      growth in the presence of 1 mM spermidine the levels of C5 protein mRNA and
      catalytic M1 RNA were significantly elevated in the wild type E. coli K-12 strain
      MG1655. 3. The rnpA mRNA, together with the ribosomal protein L34 (rpmH) mRNA,
      was found to constitute a dicistronic rpmH-rnpA message whose half-life did not
      change upon Escherichia coli growth in the presence of spermidine. 4. This
      suggests that the spermidine effect is on the transcriptional level. 5. Increased
      expression of the rnpA and rnpB genes was reflected in the activity of RNase P,
      which almost doubled. 6. These results identify yet another component of the
      protein synthetic machinery which is specifically affected by polyamines.

PMID- 1397491
TI  - Rat guanidinoacetate methyltransferase: mutation of amino acids within a common
      sequence motif of mammalian methyltransferase does not affect catalytic activity
      but alters proteolytic susceptibility.
AB  - 1. Manual alignment of amino acid sequences of mammalian S-adenosylmethionine
      dependent methyltransferases of known sequence revealed the presence of 2
      homologous regions. 2. The sequence of the region at the C-terminal side is
      unique to mammalian methyltransferases, and in guanidinoacetate methyltransferase
      this sequence occurs at residues 159-165. 3. Mutagenesis of 5 conserved residues
      in this sequence did not affect the catalytic activity but altered tryptic
      susceptibility at Arg20.

PMID- 1397492
TI  - The control of protein degradation in monolayer cultures of cat hepatocytes.
AB  - 1. Isolated cat hepatocytes were established in monolayer culture, cell proteins
      labelled with tritiated leucine and the effects of amino acids and hormones on
      the regulation of intracellular protein breakdown were studied. 2. Mixtures of
      essential and non-essential amino acids inhibited the breakdown of long-lived
      protein, but when tested individually, amino acids except for tryptophan were
      ineffective. 3. The rate of breakdown of short-lived protein was not regulated by
      amino acids or hormones, a finding which was similar to that in rat liver cells.
      4. The known stimulatory hormones of proteolysis in rat liver such as glucagon,
      dexamethasone and corticosteroids failed to enhance protein degradation in cat
      liver cells. 5. These results support the contention that the control of protein
      degradation in the cat is different to that in the rat and these differences may
      reflect the unusual protein metabolism of the cat.

PMID- 1397494
TI  - Phorbol ester induction of rat hepatic metallothionein in vivo and in vitro.
AB  - 1. The induction of metallothionein (MT) protein by TPA (O-tetradecanoyl phorbol
      acetate), a protein kinase C activator, was demonstrated in vivo in rat liver and
      in vitro in rat hepatocytes in primary culture. In vivo half maximal induction at
      25 hr was seen at 26 nmol TPA/kg body wt. Five- to seven-fold inductions were
      seen in vivo. De novo protein synthesis was required for this induction as
      demonstrated by cycloheximide inhibition of [35S]cysteine incorporation into MT
      protein. 2. TPA induction of MT protein in primary cultures of rat hepatocytes
      reached levels of 2.6-4.1-fold, as assessed by [35S]cysteine incorporation, 1.34
      2.20-fold, as assessed by 109Cd binding in a metal displacement/HPLC assay, and
      2.5-5-fold, as assessed by 109Cd binding in a metal displacement/Sephadex G-75
      Superfine assay. 3. The induction of MT mRNA by TPA was demonstrated in vivo in
      rat liver and in vitro in 2 rat hepatoma cell lines, EC3 and 2M. MT mRNA was
      quantitated using dot blot and Northern gel assays. In vivo TPA induced hepatic
      MT mRNA 2.36-5.88-fold (dot blot) and 7.4-22-fold (Northern gels). In vitro TPA
      induced MT mRNA 1.71-15.26-fold in EC3 cells and 2.23-8.43-fold in 2M cells. MT
      mRNA was 0.54 kb, and alpha-tubulin mRNA was 1.62 kb in size on Northern gels. 4.
      TPA induction of MT protein and mRNA in vivo and in vitro is rapid and persistent
      and occurs at low concentrations. The 2 rat hepatoma cell lines provide a useful
      system in which to study MT induction in vitro without confounding secondary
      effects which can occur in vivo.

PMID- 1397493
TI  - Sequence of insulin effects on cytoskeletal and cytosolic phosphofructokinase,
      mitochondrial hexokinase, glucose 1,6-bisphosphate and fructose 2,6-bisphosphate
      levels, and the antagonistic action of calmodulin inhibitors, in diaphragm
      muscle.
AB  - 1. Time-curves of insulin effects on energy-producing systems in different
      cellular compartments of rat diaphragm muscle have revealed: (a) a rapid (within
      minutes) and transient stimulatory effect of insulin on cytoskeletal
      phosphofructokinase and aldolase and mitochondrial hexokinase. (b) A slower and
      consistent stimulatory effect on glucose 1,6-bisphosphate level, with concomitant
      gradual activation of cytosolic phosphofructokinase. Fructose 2,6-bisphosphate
      levels were not changed by insulin. (c) Lactate concentration correlated with the
      stimulation of cytoskeletal and cytosolic glycolysis. 2. Calmodulin antagonists,
      trifluoperazine or CGS 9343B, prevented all these effects of insulin. 3. These
      results suggest that cytoskeletal glycolysis and mitochondrial oxidation are the
      source of ATP for the rapid actions of insulin, whereas cytosolic glycolysis is
      the source of ATP for the slow actions of insulin. Calmodulin is involved in all
      these effects of insulin.

PMID- 1397495
TI  - The effects of propionate and butyrate on acetate metabolism in rat hepatocytes.
AB  - 1. Two mM propionate or butyrate inhibited the mitochondrial uptake of acetate by
      rat hepatocytes. 2. With propionate the inhibition was so strong that the net
      formation of acetate in the cytoplasm, usually masked by the mitochondrial
      uptake, appeared directly as a net output of acetate into the medium; showing
      that this net formation of acetate, reported by [Crabtree B., Gordon M.-J. and
      Christie S. L. (1990) Biochem. J. 270, 219-225] is not an artefact arising from a
      misinterpretation of isotopic data. 3. The results also suggest that propionate
      and butyrate inhibit peroxisomal metabolism.

PMID- 1397496
TI  - Hemolysis of phosphatidylcholine-containing erythrocytes by serratamic acid from
      Serratia marcescens.
AB  - 1. The hemolysis by serratamic acid, "N-(D-3-hydroxydecanoyl)-L-serine and N-(D-3
      hydroxydodecanoyl)-L-serine", was investigated with human and animal erythrocytes
      using serratamic acid-containing liposomes. 2. The hemolytic activity was found
      to depend on the incubation temperature and the concentration of the liposomes.
      3. The concentration of serratamic acid for 50% hemolysis was 0.17 mM at 37
      degrees C for 0.2% human erythrocyte suspension in the liposomes which composed
      of phosphatidylserine, cholesteryl nervonate and serratamic acid (1:0.50:0.37 by
      mol). 4. The hemolysis was shown specifically in human, horse and rabbit
      erythrocytes containing phosphatidylcholine, but not in sheep or bovine
      erythrocytes lacking phosphatidylcholine. 5. The hemolytic activity was strongly
      inhibited by the exogenous addition of phosphatidylcholine. It was suggested that
      the hemolysis by serratamic acid-containing liposomes was specific for
      phosphatidylcholine-containing erythrocyte membranes.

PMID- 1397497
TI  - The effect of L-carnitine on cholesterol metabolism in rat (Rattus bubalus)
      hepatocyte cells.
AB  - 1. This paper concerns the study of the effect of L-carnitine on cholesterol
      metabolism in rat hepatocyte cells BRL-3A. In this research the binding of
      [125I]human low density lipoprotein (LDL) to BRL-3A cells and 3-hydroxy 3
      methylglutaryl CoA reductase activity (HMG-CoA reductase activity) after L
      carnitine incubation were studied. 2. It was found that L-carnitine is able to
      increase either the [125I]LDL binding or inhibit the HMG-CoA reductase activity
      in BRL-3A cells. 3. These results indicate that L-carnitine affects the
      cholesterol metabolism through an inhibition of HMG-CoA reductase activity that
      could be responsible for the increased [125I]LDL binding in rat hepatocytes.

PMID- 1397498
TI  - Kinetic evidence for the existence of an unstable intermediate in the
      trinitrophenylation-induced rhodanese inactivation reaction.
AB  - 1. Rhodanese inactivation by 2,4,6-trinitrobenzenesulphonate, in the presence of
      n-butylamine in the reaction medium, has been studied by a kinetic analysis of
      the data, based on the assumption that enzyme inactivation is brought about by
      direct reaction of this with the modifying agent. 2. Initial reaction rates for
      rhodanese activity loss were determined by a mathematical analysis of the first
      three recorded values of rhodanese residual activity. 3. It was found that
      fractional rhodanese activity values, at infinite reaction time with 2,4,6
      trinitrobenzenesulphonate (end-point values), were significantly lower than the
      values calculated on the assumption of rhodanese inactivation being entirely due
      to direct trinitrophenylation of enzyme protein. 4. Also, initial enzyme
      inactivation values were higher in the presence, rather than in the absence, of n
      butylamine. 5. These results indicate that 2,4,6-trinitrobenzenesulphonate
      induced rhodanese inactivation, in the presence of n-butylamine in the reaction
      medium, is due to the generation of a highly reactive, unstable intermediate,
      probably a free radical species.

PMID- 1397499
TI  - Characterization of 130 kDa protein from rat cerebellum synaptosomal membranes
      phosphorylated by PKC.
AB  - 1. The effect of endogenous PMA-stimulated phosphorylation of the protein in the
      molecular weight range of 130 kDa in rat cerebellum synaptosomal membranes was
      examined. 2. The 50% inhibition of the phosphorylation of 130 kDa protein by 5
      microM polymyxin B was observed after 6 min of preincubation. 3. The sensitivity
      of 130 kDa protein for phosphorylation in the presence of exogenous protein
      kinase C suggests, that this protein could serve as a physiological substrate of
      protein kinase C. 4. Partial characterization of 130 kDa protein was performed.
      Upon incubation with [gamma-32P]ATP the 130 kDa protein formed Ca(2+)-dependent,
      hydroxylamine-sensitive phosphointermediate, which was inhibited by 50 microM
      vanadate, but not 0.5 mM vanadyl. 5. One-dimensional peptide mapping by
      proteolysis of 130 kDa protein with V8 protease was obtained.

PMID- 1397500
TI  - In vivo effects of cadmium on rat liver glucocorticoid receptor functional
      properties.
AB  - 1. Cadmium (Cd2+) administered in vivo induced a 40% reduction of rat liver
      glucocorticoid receptor (GR) capacity and inhibition of glucocorticoid-receptor
      complexes binding to mouse mammary tumor virus (MMTV) DNA fragment containing GR
      consensus sequence. 2. The effect of Cd2+ on the GR binding activity can be
      reversed with DTT, suggesting Cd2+ interaction with thiol groups. 3. Cd(2+)
      related GR modification seems to be mediated by Cd2+ binding to cytoplasmic
      components included in the regulation of the receptor function, although the
      direct binding of the metal to the receptor thiols could not be ruled out.

PMID- 1397501
TI  - Purification and characterization of streptolysin O from Streptococcus pyogenes.
AB  - 1. Streptolysin O, an exotoxin produced by group A beta-hemolytic streptococci,
      has been purified from Streptococcus pyogenes culture supernatants. 2. The
      isolation and purification procedure involved ammonium sulphate and polyethylene
      glycol precipitations, and ion-exchange chromatographies on CM-Sepharose and Mono
      Q. 3. The proposed procedure introduces two ion-exchange chromatography steps
      making the purification process simpler and, especially, more reproducible than
      other described protocols. 4. The purified streptolysin O was hemolytically
      active, had a specific activity of 415,000 HU/mg, an optimum pH of 7.0, a
      relative molecular mass of 60,100 and an isoelectric pH of 7.5.

PMID- 1397502
TI  - Changes in the properties of honeybee haemolymph alpha-glucosidases following
      dithiothreitol dissociation of native complexes.
AB  - 1. The higher relative molecular mass (M(r)) forms of larval honeybee haemolymph
      alpha-glucosidases are dissociated by dithiothreitol (DTT) into lower M(r)
      electrophoretic forms, without any important loss of activity. 2. The maximum
      velocity remains unchanged and the apparent dissociation constant is slightly
      increased, with Ki approximately equal to 247 mM and I50 approximately equal to
      730 mM. 3. By contrast, the major changes affect the Hill coefficient which
      decreases from 1.0 in controls to 0.7 in presence of 600 mM DTT. 4. In the
      absence of both DTT and substrate, the major native enzyme form, isolated by gel
      filtration, spontaneously rearranges to give three additional minor forms, one of
      lower M(r) and two of higher M(r). 5. These data are consistent with the
      hypothesis of substrate-directed aggregation of enzyme protomers into functional
      complexes.

PMID- 1397503
TI  - The isolation and partial characterization of catalase and a peroxidase active
      fraction from human white adipose tissue.
AB  - 1. A procedure is described for the purification of catalase and a peroxidase
      active fraction from human white adipose tissue. 2. Gel electrophoresis on SDS
      PAGE revealed relative molecular masses of 202,900 and 208,600 for the active
      catalase and peroxidase molecules respectively (nonreducing conditions), as
      compared to 56,800 and 49,800 for the monomers under reducing conditions, thus
      indicating the likelihood of tetramers in the intact state. 3. The two purified
      enzymes differ with regard to pH optima (5-9 for catalase and 3 for peroxidase),
      temperature stability (up to 50 degrees C for catalase and 70 degrees C for
      peroxidase) and Km values towards H2O2 (38.9 mM for catalase and 7.69 mM for
      peroxidase, which was also active in oxidizing a number of o-dihydricphenols as
      second substrates). 4. The catalase enzyme showed uncompetitive inhibition by the
      irreversible inhibitor 3-amino-1,2,4-triazole (AT), Ki = 5.4 mM.

PMID- 1397504
TI  - Beta-oxidation as channeled reaction linked to citric acid cycle: evidence from
      measurements of mitochondrial pyruvate oxidation during fatty acid degradation.
AB  - 1. The kinetics of mitochondrial mammalian pyruvate dehydrogenase multienzyme
      complex (PDHC) is studied by the formation of CO2 using tracer amounts of [1
      14C]pyruvate. It is found that the Hill plot results in a (pseudo-)cooperativity
      with a transition of n-1----3 at a pyruvate concentration about Ks. 2. Addition
      of L-carnitine, octanoate, palmitoyl-CoA or palmitate + L-carnitine + fatty acid
      binding protein results in a Hill coefficient of n = 2 following the kinetics of
      pyruvate oxidation. 3. Addition of fatty acid-binding protein to an assay system
      oxidizing palmitate in presence of L-carnitine alters the pattern of the kinetics
      in the Hill plot so that an apparently lower level of L-carnitine is necessary
      for the reaction course of beta-degradation. 4. It is concluded that beta
      degradation is a coordinated, multienzyme-complex based mechanism tightly linked
      to citric acid cycle and it is proposed that L-carnitine is actively involved
      into the reaction and not only functioning as carrier-molecule for transmembrane
      transport.

PMID- 1397505
TI  - Physiological state and the sensitivity of liver mitochondrial outer membrane
      carnitine palmitoyltransferase to malonyl-CoA. Correlations with assay
      temperature, salt concentration and membrane lipid composition.
AB  - 1. Liver mitochondrial outer membranes were pre-exposed to media of low (20 mM
      phosphate) or high salt concentration (20 mM phosphate + 0.3 M KCl) before assay
      of carnitine palmitoyltransferase (CPT) at 25 degrees C. 2. With membranes from
      fed rats, exposure to high salt decreased sensitivity of CPT to malonyl-CoA
      whereas high salt increased sensitivity of CPT to malonyl-CoA in membranes from
      48 hr-fasted rats. These changes were paralleled by alterations in the KD for
      high affinity binding of [14C]malonyl-CoA to outer membranes. 3. Decreasing the
      CPT assay temperatures from 25 to 10 degrees C caused qualitatively similar
      changes to those seen on exposure to high salt. 4. The relative content of
      sphingomyelin was increased 2-fold and 4-fold in liver mitochondrial outer
      membranes from fasted and diabetic rats respectively. Fasting had no effect on
      the content of cholesterol whereas diabetes decreased this by a third.

PMID- 1397507
TI  - Proteolysis at pressure and HPLC peptide mapping of M4-lactate dehydrogenase
      homologs from marine fishes living at different depths.
AB  - 1. The effects at 10 degrees C of moderate hydrostatic pressure (136 atm) on
      trypsinolysis of muscle-type (M4) lactate dehydrogenase homologs (LDH, EC
      1.1.1.27, L-lactate:NAD+ oxidoreductase) from shallow- and deep-occurring marine
      fishes were examined by mapping the partial digests by reverse phase HPLC. 2.
      Comparison of peptide maps of digests generated at 1 and 136 atm revealed that
      increased pressure did not expose new cleavage sites in homologs of any of the
      species; no new peptides were generated. 3. Increased pressure did alter the
      relative amounts of peptides produced. The net effect of increased pressure was
      to increase the amount of peptides generated in the shallow-occurring species.
      For deep-living species pressure did not alter the net amount of peptides
      produced compared to the 15 min atmospheric pressure samples, although the
      relative amounts of some of the peptides changed. Incubation at 136 atm for 30
      min decreased the net amount of peptides produced. 4. It is suggested that the
      effects of pressure on trypsinolysis may result from slight conformational
      changes in the substrate proteins.

PMID- 1397506
TI  - Ribosomes from trichomonad protozoa have prokaryotic characteristics.
AB  - 1. Ribosomes from cells of the genera Trichomonas and Tritrichomonas have been
      isolated and characterized. The ribosomes from each organism had a sedimentation
      coefficient of 70S in calibrated sucrose gradients and the subunits sedimented as
      50S and 30S particles under the same conditions. 2. The major ribosomal RNAs from
      each species were identical in size to prokaryotic ribosomal RNAs when examined
      by denaturing gel electrophoresis. The ribosomes contained both 5.8S and 5S RNAs.
      3. The ribosomal proteins were compared by the methods of two-dimensional gel
      electrophoresis and reversed phase HPLC. Electrophoresis of the ribosomal
      proteins in two different gel systems indicated the presence of 56 proteins in T.
      gallinae, 40 in T. bactrachorum and 45 in the Tritrichomonas sp. The protein
      molecular mass range was 8.5-40 kDa. 4. The HPLC analysis confirmed the protein
      number established by the gel methods. 5. Both methods of analysis revealed
      greater similarities between the ribosomal proteins of the 2 Tritrichomonas sp.
      than between those of the more distantly related T. gallinae and T. bactrachorum.

PMID- 1397508
TI  - Purification and characterization of a glycosylated proline-rich protein from
      human parotid saliva.
AB  - 1. A glycosylated proline-rich protein (GPRP) was purified to homogeneity by
      subjecting parotid saliva to immunoaffinity, cation exchange, affinity and
      hydrophobic chromatography. 2. The purified GPRP had a molecular weight of 78 kDa
      as analyzed by SDS-PAGE. 3. The amino acid analysis revealed a preponderance of
      proline, glycine and glutamic acid/glutamine, which accounted for 77% of the
      total amino acids. 4. Cysteine, tyrosine or phenylalanine residues were not
      detected. 5. The glycoprotein contained 34% neutral sugars and the
      oligosaccharides were rich in mannose and N-acetylglucosamine, indicating that N
      linked oligosaccharides were the predominant type of oligosaccharides in the
      molecule. 6. These observations were confirmed by treatment of the purified
      glycoprotein with specific N-glycosidase which removed the N-linked
      oligosaccharides leaving a core protein with an apparent molecular weight of 51
      kDa. 7. The isoelectric point of GPRP was approx 7.0 and the molecule was not
      affected by reduction with 2-mercaptoethanol, indicating that no disulfide
      linkages were present. 8. The GPRP bound to hydroxyapatite and this binding could
      be partially inhibited by preincubation of the hydroxyapatite with parotid or
      submandibular saliva. 9. The purified GPRP also bound to a protein with an
      apparent molecular weight of 95 kDa present in submandibular saliva.

PMID- 1397509
TI  - Kinetic behaviour and properties of aldehyde dehydrogenase from rat testis
      mitochondria. Effect of Mg2+ ions.
AB  - 1. Mitochondrial aldehyde dehydrogenase is purified to near homogeneity by
      hydroxylapatite-, affinity- and hydrophobic interaction-chromatography. 2. The
      enzyme is an oligomeric protein and its molecular weight, as determined by gel
      filtration, is 117,000 +/- 5000. 3. Active only in the presence of exogenous
      sulfhydryl compounds and NAD(+)-dependent, aldehyde dehydrogenase works optimally
      with linear-chain aliphatic aldehydes and is practically inactive with
      benzaldehyde. The pH-optimum is at about pH 8.5. 4. Km-Values for aliphatic
      aldehydes (C2-C6) range between 0.17 and 0.32 microM. The Km for NAD+ increases
      from 16 microM with acetaldehyde to 71 microM with capronaldehyde. 5. Millimolar
      concentrations of Mg2+ promote high increases of both V and Km for NAD+. At the
      same time, saturation curves with C4-C6 aldehydes can be simulated with a
      substrate inhibition model. 6. Inhibition by NADH is competitive: with
      capronaldehyde, the inhibition constant for NADH is 52 microM in the absence of
      Mg2+ and 14 microM in the presence of 4 mM Mg2+; with acetaldehyde, the
      inhibition constant is about three times higher (36 and 159 microM,
      respectively).

PMID- 1397510
TI  - Cholesterol metabolism in cultured hamster hepatocytes.

PMID- 1397511
TI  - Direct measurement of apo B-100 production rate in fed and fasted normolipidaemic
      adult male volunteers.

PMID- 1397512
TI  - Very low density lipoprotein apolipoproteins B-100 and E turnover in control
      subjects using L-[1-13C]-leucine.

PMID- 1397513
TI  - Fractional and absolute synthetic rate of very low density lipoprotein apo B-100
      in lipoprotein lipase deficient patients.

PMID- 1397514
TI  - Metabolic comparison of small chylomicrons (intestinal VLDL) and large
      chylomicrons.

PMID- 1397515
TI  - Removal of cholesterol from the rat spleen by phospholipid-apolipoprotein
      mixtures.

PMID- 1397516
TI  - Arylamine N-acetyl transferase in mice.

PMID- 1397517
TI  - Measurement of human brain aspartate N-acetyl transferase flux in vivo.

PMID- 1397518
TI  - Homology between cellobiose oxidase from Phanerochaete chrysosporium and other
      proteins.

PMID- 1397519
TI  - Expression of active horseradish peroxidase in Saccharomyces cerevisiae.

PMID- 1397520
TI  - Properties of the oxygenase responsible for plant ethylene production.

PMID- 1397521
TI  - N-glycosylation of horseradish peroxidase from cell culture.

PMID- 1397522
TI  - Investigation of native and mutant plant peroxidases by NMR spectroscopy.

PMID- 1397523
TI  - Mechanism of pyrimidine nucleoside uptake in intestinal brush border membrane
      vesicles.

PMID- 1397524
TI  - Identification of a fatty acid-binding protein in human prostatic tissue.

PMID- 1397525
TI  - Membrane accommodation in hypo-osmotically-treated, and in giant electrofused
      cells.

PMID- 1397526
TI  - Talin-lipid interaction.

PMID- 1397527
TI  - FT-IR study of the hydrogen bonding interaction between cholesterol and DPPC.

PMID- 1397528
TI  - Characterisation of diffusion and flow of receptors on cell membranes by digital
      fluorescence microscopy.

PMID- 1397529
TI  - Production of HETEs in human neutrophils; dependence of arachidonic acid.

PMID- 1397530
TI  - ATP and glutathione mediated inhibition of lipid peroxidation in rat liver
      systems.

PMID- 1397531
TI  - Evidence for a novel mechanism of activation of phospholipase D by endothelin-1
      in neuroblastoma cells.

PMID- 1397532
TI  - Activation by anserine and inhibition by carnosine of Ca(2+)-uptake by mammalian
      mitochondria.

PMID- 1397533
TI  - Properties and [32P] phosphorylation targets of a novel form of protein kinase C
      in pituitary.

PMID- 1397534
TI  - Blackcurrant seed oil as a source of polyunsaturated fatty acids in the treatment
      of inflammatory disease.

PMID- 1397535
TI  - Purinergic stimulation of phosphatidic acid accumulation is via two pathways in
      bovine aorta endothelial cells.

PMID- 1397536
TI  - Effect of staurosporine derivatives on IL-1-stimulated prostaglandin E
      production.

PMID- 1397537
TI  - Expression of recombinant firefly luciferase in prokaryotic and eukaryotic cells.

PMID- 1397538
TI  - Engineering aequorin to measure Ca2+ in defined compartments of living cells.

PMID- 1397539
TI  - Pharmacological characterisation of the 5-HT1A serotonin receptor using the
      agonist [3H]8-OH-DPAT, and the antagonist [3H]spiperone.

PMID- 1397540
TI  - Structural analysis of the D2 dopamine receptor.

PMID- 1397541
TI  - Receptor-specific antisera as probes for the D2-dopamine receptor.

PMID- 1397542
TI  - Three dimensional models of the rat D2, D3 and D4 dopamine receptors.

PMID- 1397543
TI  - Molecular biology of calmodulin in the Eucestoda.

PMID- 1397544
TI  - Fast atom bombardment mass spectrometric analysis of cyclic nucleotides.

PMID- 1397545
TI  - Characterisation of two novel glycoproteins in the membrane skeleton of the
      growth cone.

PMID- 1397546
TI  - The structural relationship between the two synapse enriched glycoproteins, GP65
      and GP55.

PMID- 1397547
TI  - Benzodiazepine-induced changes in biomembrane fluidity.

PMID- 1397548
TI  - Anchorage of asymmetric acetylcholinesterase by isodipeptide crosslinking in
      muscle cells.

PMID- 1397549
TI  - Cloning, expression, and mutagenesis of SIVmac proteinase in E. coli.

PMID- 1397550
TI  - Use of chemical cleavage to release active HIV-1 proteinase from a fusion protein
      produced in the form of insoluble inclusion bodies.

PMID- 1397551
TI  - Sulphated polysaccharides exert anti-HIV activity at differing sites.

PMID- 1397552
TI  - A specific antibody to apolipoprotein B-48: a novel approach.

PMID- 1397553
TI  - Purification of human foetal hepatic bile acid sulphotransferase (BAST).

PMID- 1397554
TI  - Glycerol 3-phosphate acylation by microsomal fractions from avocado mesocarp.

PMID- 1397555
TI  - Induction of delta 12-desaturase activity during temperature adaptation in
      Acanthamoeba castellanii.

PMID- 1397556
TI  - Triacylglycerol synthesis by microsomal fractions from olive cultures.

PMID- 1397558
TI  - The effect of coronary artery ligation on the energy status of the rat heart.

PMID- 1397557
TI  - Changes in the myocardial creatine kinase isozyme profile with progression and
      regression of volume overload eccentric hypertrophy.

PMID- 1397559
TI  - Phosphatidylserine decarboxylase activity during the early phases of regeneration
      in the rat liver.

PMID- 1397560
TI  - Immunomodulatory action of amino acids on lymphocyte blastogenesis.

PMID- 1397562
TI  - Determination of the presence of low levels of male DNA against high level female
      DNA background.

PMID- 1397561
TI  - Partial characterisation of brushborder membrane bound iron binding protein of
      guinea pig enterocytes.

PMID- 1397563
TI  - Reaction of some beta-amino acids with ninhydrin and with two related triketones.

PMID- 1397564
TI  - A study of the phospholipid composition of vegetables by using 31P-NMR.

PMID- 1397565
TI  - The mutation in the normal F variant of alpha-1-antitrypsin (Arg223----Cys)
      determined by DNA amplification and direct sequencing.

PMID- 1397566
TI  - The expression of the Na+/glucose cotransporter in the lamb small intestine.

PMID- 1397567
TI  - Fractionation of rat urinary proteins by sequential ultrafiltration.

PMID- 1397568
TI  - Urinary protein patterns in autism as revealed by high resolution two-dimensional
      electrophoresis.

PMID- 1397570
TI  - Clenbuterol induces a propranolol-sensitive accumulation of actin message in rat
      skeletal muscle.

PMID- 1397569
TI  - Isolation and biochemical characterization of protein kinase C from rat mammary
      gland.

PMID- 1397571
TI  - A modified method for the isolation of beta B2-crystallin from the bovine lens:
      removal of glutathione.

PMID- 1397572
TI  - Iron chelate affinity chromatography of brush border membrane proteins.

PMID- 1397573
TI  - Cardiac glucose metabolism during pregnancy.

PMID- 1397574
TI  - Skeletal muscle glucose utilization in response to a decreased meal frequency.

PMID- 1397575
TI  - Glucose utilization by skeletal muscle during pregnancy.

PMID- 1397577
TI  - Conformational studies on human transferrin.

PMID- 1397576
TI  - Studies on the role of ascorbic acid in olfactory tissue.

PMID- 1397578
TI  - Binding of 5 alpha-androst-16-en-3-one to pig olfactory tissue.

PMID- 1397579
TI  - Proteoglycans: a regulatory role in the proliferation of intestinal epithelia.

PMID- 1397580
TI  - Heparin modulation of cellular proliferative responses: kinetic and concentration
      dependency.

PMID- 1397581
TI  - Identification of a human brain peptidase with the specificity to generate the N
      terminus of A4/beta-amyloid protein from its precursor.

PMID- 1397582
TI  - Effect of dexamethasone on collagen synthesis in fibroblasts cultured in collagen
      lattice.

PMID- 1397583
TI  - Heat-stabilizing factor of lactate dehydrogenase in the skeletal muscle of
      Uromastix.

PMID- 1397584
TI  - Low molecular weight proteoglycans from renal stones.

PMID- 1397585
TI  - Attempts to provide an insight into the anti-cataract effect of ibuprofen.

PMID- 1397586
TI  - Toxicity of dipropyl sulphoxide.

PMID- 1397587
TI  - 13C-n.m.r. spectroscopy of Cu(2+)-heparin suggests phase separation of the
      complex from Cu2+ in aqueous solution.

PMID- 1397588
TI  - Examination of cation-heparin interaction by potentiometric titration.

PMID- 1397589
TI  - Effect of chemically modified heparins, and of heparin fragments, on Fe(II)
      catalyzed peroxidation of linolenic acid.

PMID- 1397591
TI  - Purification of ent-kaurene oxidase from Gibberella fujikuroi and Cucurbita
      maxima.

PMID- 1397590
TI  - Purification and characterization of 5-HT3 receptors from NG108-15 neuroblastoma
      x glioma cells.

PMID- 1397592
TI  - 2-Aminoethylphosphonic acid is the main phosphorus compound in locust haemolymph.

PMID- 1397593
TI  - Microbial-dependent gamma delta receptor-bearing T-cell localization?

PMID- 1397594
TI  - The leukocyte common antigen T200 glycoprotein in T-cell triggering.

PMID- 1397595
TI  - Properties of plant peroxygenase.

PMID- 1397596
TI  - CATS and biochemistry at Wolverhampton Polytechnic.

PMID- 1397597
TI  - Ligninolytic enzymes produced by two white-rot fungi.

PMID- 1397598
TI  - Production of cellulases by an isolated fungus and its mutant strain.

PMID- 1397599
TI  - Cellulase production by thermophilic fungi.

PMID- 1397601
TI  - Evidence for coniferyl-alcohol oxidase promotion of lignification in developing
      xylem of conifers.

PMID- 1397600
TI  - Does an antibody molecule act as a template directing (determining) its
      glycosylation?

PMID- 1397602
TI  - The use of specific antivasopressin antisera to detect immunoreactive vasopressin
      in human skeletal muscle.

PMID- 1397603
TI  - Effect of aspirin, flurbiprofen and indomethacin on porcine testicular
      steroidogenesis.

PMID- 1397604
TI  - Antioxidants protect against reoxygenation-induced cell damage in ventricular
      myocytes.

PMID- 1397605
TI  - Ciba Medal Lecture. Eukaryotic cell-cycle control.

PMID- 1397606
TI  - Colworth Medal Lecture. Glycosyl-phosphatidylinositol membrane anchors: the tale
      of a tail.
AB  - Over the last few years we have learned of a new type of membrane anchorage for
      cell-surface proteins, the GPI anchors. We now have a good idea of their
      structure and biosynthesis, and indications of their specific functions in
      protozoa and mammals. The widespread distribution of GPI membrane anchors
      throughout the eukaryotes has led many researchers to work on various aspects of
      GPI anchors. This has led to the widespread exchange of data, ideas and
      techniques which has made the field a pleasure to work in.

PMID- 1397607
TI  - A tribute to Elvin A. Kabat.

PMID- 1397608
TI  - Studies of oligosaccharide and glycoprotein conformation.

PMID- 1397609
TI  - Glycosylation of nuclear and cytoplasmic proteins is ubiquitous and dynamic.

PMID- 1397611
TI  - Role of glycosylation in cell interactions with extracellular matrix.

PMID- 1397610
TI  - Nuclear and cytoplasmic localization of a lectin-ribonucleoprotein complex.

PMID- 1397613
TI  - The lipo-oligosaccharidic symbiotic signals of Rhizobium meliloti.

PMID- 1397612
TI  - Changes in cell-surface carbohydrate during terminal differentiation of human
      epidermal keratinocytes.

PMID- 1397614
TI  - Sulphated glycoconjugates in the immune system.

PMID- 1397615
TI  - Regulation of pineal serotonin N-acetyltransferase activity.

PMID- 1397616
TI  - Arylamine N-acetyltransferase.

PMID- 1397617
TI  - Breast cancer: a model system for studying the neuroendocrine role of pineal
      melatonin in oncology.

PMID- 1397618
TI  - Melatonin: the clinical perspective in man.

PMID- 1397619
TI  - An overview of CATs development across the U.K.

PMID- 1397620
TI  - Credit accumulation and transfer schemes.

PMID- 1397621
TI  - Credit accumulation and transfer: a view from the chalkface.

PMID- 1397622
TI  - An institutional view of credit accumulation and transfer.

PMID- 1397623
TI  - Credit accumulation and transfer schemes--the European and company dimensions.

PMID- 1397624
TI  - Plant peroxidase gene expression and function.

PMID- 1397625
TI  - Structure of plant and fungal peroxidases.

PMID- 1397626
TI  - Probing the mechanism of horseradish peroxidase by site-directed mutagenesis.

PMID- 1397627
TI  - Catalytic mechanisms and regulation of lignin peroxidase.
AB  - Lignin peroxidase (LiP) is a fungal haemoprotein similar to the lignin
      synthesizing plant peroxidases, but it has a higher oxidation potential and
      oxidizes dimethoxylated aromatic compounds to radical cations. It catalyses the
      degradation of lignin models but in vitro the outcome is net lignin
      polymerization. LiP oxidizes veratryl alcohol to radical cations which are
      proposed to act by charge transfer to mediate in the oxidation of lignin.
      Phenolic compounds are, however, preferentially oxidized, but transiently
      inactivate the enzyme. Analysis of the catalytic cycle of LiP shows that in the
      presence of veratryl alcohol the steady-state turnover intermediate is Compound
      II. We propose that veratryl alcohol is oxidized by the enzyme intermediate
      Compound I to a radical cation which now participates in charge-transfer
      reactions with either veratryl alcohol or another reductant, when present.
      Reduction of Compound II to native state may involve a radical product of
      veratryl alcohol or radical product of charge transfer. Phenoxy radicals, by
      contrast, cannot engage in charge-transfer reactions and reaction of Compound II
      with H2O2 ensues to form the peroxidatically inactive intermediate, Compound III.
      Regulation of LiP activity by phenolic compounds suggests feedback control, since
      many of the products of lignin degradation are phenolic. Such control would lower
      the concentration of phenolics relative to oxygen and favour degradative ring
      opening reactions.

PMID- 1397628
TI  - A comparison of peroxidase and cytochrome P-450.
AB  - A peroxidase has 1-electron oxidation as its characteristic activity, while that
      of cytochrome P-450 is hydroxylation. Both catalytic cycles involve similar high
      valency states of iron. However, a peroxidase can only accept electrons at the
      haem edge, while the substrate for cytochrome P-450 is bound in a precise
      orientation before the active state is created.

PMID- 1397629
TI  - Function, mechanism and regulation of cytochrome P-450 enzymes in plants.

PMID- 1397631
TI  - The nature and regulation of the alternative oxidase of plant mitochondria.

PMID- 1397630
TI  - Endogenous and engineered cytochrome P-450 mono-oxygenases in plants.

PMID- 1397632
TI  - Structural studies on copper-containing plant oxidases.

PMID- 1397633
TI  - Copper-containing plant oxidases.

PMID- 1397634
TI  - Molecular cloning of neuronal calmodulin mRNA species.

PMID- 1397635
TI  - Comparative glycosylation in neural adhesion molecules.

PMID- 1397636
TI  - Glycoproteins of the growth-cone membrane skeleton.

PMID- 1397637
TI  - Contact inhibition of growth-cone motility during peripheral nerve segmentation.

PMID- 1397639
TI  - The changing role of NCAM as a neurite outgrowth-promoting molecule during
      development.

PMID- 1397638
TI  - Glycoproteins implicated in neural cell adhesion and axonal growth.

PMID- 1397640
TI  - Glycoproteins modulate changes in synaptic connectivity in memory formation.

PMID- 1397641
TI  - Protein kinase C.

PMID- 1397642
TI  - The design and biological properties of potent and selective inhibitors of
      protein kinase C.

PMID- 1397643
TI  - Polyisoprenoid synthesis and metabolism.

PMID- 1397644
TI  - Geranylgeranylated proteins.

PMID- 1397645
TI  - Expression of polyisoprenylated Ras proteins in the insect/baculovirus system.

PMID- 1397646
TI  - p21ras farnesyltransferase: purification and properties of the enzyme.

PMID- 1397647
TI  - Protein prenyltransferases.

PMID- 1397648
TI  - Partial characterization of p21ras farnesyltransferase present in human placental
      tissue.

PMID- 1397649
TI  - Lipid modifications and function of the ras superfamily of proteins.

PMID- 1397651
TI  - HIV proteinase inhibitors.

PMID- 1397650
TI  - Targeting lamin proteins to the nuclear envelope: the role of CaaX box
      modifications.

PMID- 1397652
TI  - The HIV-1 nef gene product.

PMID- 1397653
TI  - CD4 antagonists.

PMID- 1397654
TI  - Discovery and characterization of an HIV-1 Tat antagonist.
AB  - Ro 5-3335, 7-chloro-5-(2-pyrryl)-3H-1,4-benzo-diazepin-2-(H)-one, has been shown
      to inhibit gene expression controlled by the human immunodeficiency virus-1 (HIV
      1) LTR promoter. The inhibition was specific for the viral transcriptional
      transactivator Tat. The compound did not inhibit the basal activity of the HIV-1
      LTR or the activity of promoters not responsive to Tat. Consistent with its mode
      of action, Ro 5-3335 inhibited HIV-1 replication (IC50 = 0.1-1 microM) by
      reducing viral RNA synthesis in acutely, as well as chronically, infected cells
      in vitro. The compound was active against HIV-1 and HIV-2, and AZT-resistant
      clinical isolates.

PMID- 1397655
TI  - Thermodynamics of filamin-actin interaction.

PMID- 1397656
TI  - Characterisation of formic acid-derived cell membrane complex proteins from wool.

PMID- 1397657
TI  - Glycosylation of recombinant chimeric and human serum IgA1.

PMID- 1397658
TI  - Changes in concentrations of ATP and other nucleotides in erythrocytes during
      erythropoietin treatment in haemodialysis patients.

PMID- 1397659
TI  - Loss of sialic acid O-acetylation in human colorectal cancer cells.

PMID- 1397660
TI  - Loss of sulphate in human colonic mucins during ulcerative colitis.

PMID- 1397661
TI  - Proteoglycan synthesis by human mesangial cells is depressed by hyperglycaemic
      glucose concentrations.

PMID- 1397662
TI  - Steady state measurement of glomerular proteoglycan synthesis in streptozotocin
      induced diabetes.

PMID- 1397663
TI  - Secretion of multiple forms of tissue kallikrein in rat submandibular gland is
      influenced by the animals' sex and type of autonomic nerve impulse.

PMID- 1397664
TI  - Isolation of triacylglycerol synthase activity from Streptomyces lividans.

PMID- 1397665
TI  - Postprandial lipoprotein metabolism in obese patients with moderate
      hypertriglyceridaemia: effects of gemfibrozil.
AB  - After an oral fat load of 1 g/kg body weight in 10 obese females with
      hyperlipoproteinaemia type IV, serum triglycerides concentrations were maximal at
      4 h with a slight decline at 6 h, whereas serum cholesterol concentrations rose
      slightly at 4 h and 6 h. After 6 h, concentrations of triglycerides and
      cholesterol were significantly increased in chylomicrons and very low-density
      lipoprotein (VLDL), whereas cholesterol concentrations were decreased in high
      density lipoprotein 2 (HDL2) plus HDL3. After oral treatment with 450 mg
      gemfibrozil twice daily for 28 days, triglyceride concentrations were reduced in
      serum, chylomicrons, VLDL and low-density lipoprotein, and total cholesterol
      concentrations were reduced in serum, chylomicrons and VLDL, and increased in
      HDL2 plus HDL3. At 6 h after a fat load following 28 days' gemfibrozil treatment,
      triglyceride and cholesterol concentrations were reduced in serum, chylomicrons
      and VLDL when compared with pretreatment results. It is concluded that
      gemfibrozil is effective in lowering triglycerides and cholesterol, particularly
      in triglyceride-rich particles, and raising the cholesterol content of HDL2 plus
      HDL3. After an oral fat load gemfibrozil inhibits the increase in serum
      cholesterol and partly prevents postprandial hypertriglyceridaemia.

PMID- 1397666
TI  - A comparative study of nicardipine and pindolol as second-line treatments in
      essential hypertension.
AB  - A controlled, randomized, single-blind, parallel-group study compared the effects
      of nicardipine hydrochloride/hydrochlorothiazide (HCTZ) with those of
      pindolol/HCTZ in treatment of essential hypertension. The study included 43
      patients aged 30-64 years with supine diastolic blood pressures between 95 and
      125 mmHg at baseline. Patients initially received 50 mg/day HCTZ for 6 weeks and
      those patients whose diastolic blood pressure remained at or above 90 mmHg at
      week 6 (n = 29) completed a 6-week comparative phase in which they were given, in
      addition, either 30 mg nicardipine hydrochloride or 5 mg pindolol three times
      daily. Nicardipine was more effective than pindolol as a second-line treatment in
      controlling blood pressure but, because patients who were treated with
      nicardipine/HCTZ had higher baseline blood pressures, significance was lost when
      results were adjusted for the baseline blood pressure values. Treatment was
      described as 'very good' by 71.4% of patients in the nicardipine/HCTZ group and
      by 53.9% of those in the pindolol/HCTZ group; thus, both second-line
      antihypertensives were well accepted. Although 45% of patients in of each
      treatment group reported treatment-related adverse events, none experienced
      postural hypotension and no adverse event was unexpected.

PMID- 1397667
TI  - Natural cartilage polysaccharides for the treatment of sun-damaged skin in
      females: a double-blind comparison of Vivida and Imedeen.
AB  - Evidence is accumulating that cartilage polysaccharides derived from marine fish
      have a repairing effect on solar elastosis. In a double-blind trial, the efficacy
      and safety of two commercial preparations, Vivida and Imedeen, were compared in
      the treatment of sun-damaged skin in women aged 40-60 years. A group of 15 women
      received 500 mg/day Vivida and another 15 women received 380 mg/day Imedeen
      orally for 90 days. Subjective assessment revealed statistically significant
      improvements in skin condition in both treatment groups but Vivida was
      significantly (P less than 0.01) more effective than Imedeen for all parameters.
      In the Vivida group, mean epidermal thickness increased from 0.14 to 0.26 mm,
      dermal thickness from 0.90 to 1.51 mm and the elasticity index from 47% to 71%.
      In the Imedeen group, epidermal thickness increased from 0.13 to 0.18 mm, dermal
      thickness from 0.80 to 0.97 mm and the elasticity index from 48% to 56%. After 90
      days, the differences between the two groups for all three parameters were
      statistically significant (P less than 0.001). The mean erythemal index decreased
      from 0.24 to 0.20 in the Vidida group, but increased from 0.23 to 0.25 in the
      Imedeen group. In the Vivida group, five patients developed transient, mild
      pimples during the first weeks of treatment, but no other adverse effects
      occurred.

PMID- 1397668
TI  - Zinc gluconate and the common cold: a controlled clinical study.
AB  - A report in 1984 on the success of zinc gluconate against common cold symptoms
      could not be confirmed in three subsequent studies, which are now known to have
      used formulations that inactivated zinc. A non-chelating formulation including
      glycine, which releases 93% of contained zinc into saliva, was tested in a
      randomized, placebo-controlled, double-blind trial in 73 young adults. Efficacy
      was recorded in symptom diaries using a symptom severity rating. Patients'
      symptoms first appeared 1.34 days prior to entry to the study in both groups.
      Disappearance of symptoms occurred after an additional 4.9 days for zinc-treated
      patients versus 6.1 days for placebo-treated patients. A difference was noted in
      the efficacy of treatment if it was started 1 day after symptom onset: cold
      duration was an additional 4.3 days in zinc-treated patients compared with 9.2
      days for placebo-treated patients. Cough, nasal drainage and congestion were the
      symptoms most affected, and only mild side-effects were noted.

PMID- 1397669
TI  - Typhoid Vi: a less reactogenic vaccine.
AB  - A typhoid vaccine derived from the purified Vi capsular polysaccharide (CPS)
      antigen of Salmonella typhi was compared with a heat-killed whole-cell typhoid
      vaccine in 637 healthy male volunteers. The individuals were placed in three
      groups: group 1 received two doses of heat-killed whole-cell typhoid vaccine, at
      an interval of 28 days; group 2 received a single dose of typhoid Vi CPS vaccine
      followed after 28 days by water for injection; and group 3 received water for
      injection on the first occasion and a single dose of typhoid Vi CPS vaccine 28
      days later. Local and systemic adverse reactions were recorded for 5 days
      following each injection. Subjects receiving the typhoid Vi CPS vaccine
      complained of fewer local adverse reactions on each of the first 3 days following
      immunization: on day 1, 18.6% of subjects given typhoid Vi CPS vaccine reported
      local reactions compared with 59.7% of those receiving heat-killed whole-cell
      vaccine (P less than 0.001). The percentage of subjects receiving the heat-killed
      whole-cell vaccine who complained of systemic reactions was more than twice that
      of subjects receiving the Vi CPS vaccine (7.9% and 3.4%, respectively, on day 1;
      P less than 0.01).

PMID- 1397670
TI  - Cytogenetic analysis of bone marrow from patients with primary myelodysplastic
      syndrome.
AB  - Of 34 patients with primary myelodysplastic syndrome (MDS), 26 (76.5%) were found
      to have chromosome defects using an improved bone marrow culture method and high
      resolution G-banding technique induced by actinomycin D. The frequency of
      abnormalities varied among the subtypes: 1/2 in refractory anaemia with ringed
      sideroblasts; 18/24 in refractory anaemia; 5/6 in refractory anaemia with excess
      of blasts (RAEB); and 2/2 in refractory anaemia with excess of blasts in
      transformation. The most frequent abnormalities, either single, double or complex
      defects, were -5/5q-, -7, +8 and +21; 16q-/16p-, +19 and -X were also common. The
      percentage of aneuploid cells, in particular hypodiploid cells, was increased.
      The abnormalities were detected more frequently in complex aberrations associated
      with RAEB and RAEB in transformation. The presence of -5/5q- as a sole aberration
      was associated with longer mean survival time (greater than 18 months) but
      multiple (more than two) chromosomal abnormalities were associated with a poorer
      prognosis and a mean survival time of only 7.5 months. Chromosome follow-up
      studies indicated that patients with -7, +8, +21, -X and complex defects,
      increased hypodiploid cells and karyotpic evolution were likely to have a high
      risk of transformation to leukaemia or to a more severe subtype of MDS with a
      short overall mean survival time. These defects, mostly of the deleted type, are
      assumed to play a specific role in the pathogenesis of myelodysplasia. Repeated
      chromosomal analyses during the clinical course convey more accurate prognostic
      criteria for patients.

PMID- 1397671
TI  - Effects of pimobendan (UDCG 115) on renal function in healthy volunteers.
AB  - A phase I, double-blind, single-dose, randomized, two-period crossover study was
      conducted to investigate the effects of pimobendan on renal function to assess
      whether renal events were a contra-indication to its administration. Results in
      eight healthy volunteers indicated no significant adverse events on renal plasma
      flow, glomerular filtration rate, or laboratory safety screens; side-effects were
      also found to be minimal. Further studies are indicated to assess whether, in the
      proposed treatment group, i.e. patients with heart failure (in whom compromised
      renal function is common), pimobendan similarly elicits no serious adverse renal
      effects.

PMID- 1397672
TI  - An oral approach to the treatment of photodamaged skin: a pilot study.
AB  - In recent publications much attention has focused on skin changes as a
      consequence of ageing. During life many internal and external factors have an
      influence on the condition of the skin but ultraviolet radiation seems to be a
      major factor in both benign and malignant alterations. To retard the
      deterioration process, more than cosmetic concern is necessary. In a pilot study,
      a fish protein product is shown to have the capacity to ameliorate, both
      objectively and subjectively, the symptoms of photo-aged skin. Recommendations
      are made for further evaluation.

PMID- 1397673
TI  - Results of long-term follow-up after compensated fixed-dose therapy for
      thyrotoxicosis.
AB  - To evaluate the effects of simple compensated fixed-dose iodine-131 therapy for
      thyrotoxicosis, the long-term results for 74 patients treated with a fixed dose
      of iodine-131 ranging from 5 to 12 mCi (185 to 444 MBq) were evaluated in the
      first 2 years of a trial. The dose selected was loosely based on the gross size
      of the thyroid gland. Routine antithyroid drug therapy was given for a minimum of
      3 months after iodine-131 therapy. The mean (+/- SD) duration of follow-up was
      74.5 +/- 42 months. The results indicated that roughly 25% of patients treated in
      this way will become hypothyroid after 5 years and that 85% are cured (need no
      further therapy during the follow-up period) using a single dose of iodine-131.
      Of those cured using a single iodine-131 dose, 81% were no longer receiving drugs
      after 6 months and 85% after 1 year. Such a regimen seems currently to be among
      the best available where prolonged periods of medication-free euthyroidism after
      therapy are sought.

PMID- 1397674
TI  - Platelet angiotensin II in cerebrovascular accident and the effect of angiotensin
      converting enzyme inhibitors.
AB  - Platelet angiotensin II concentrations were significantly (P less than 0.01)
      elevated in 16 patients with a history of cerebral infarction, compared with 12
      control subjects. The angiotensin-converting enzyme inhibitors, captopril,
      enalapril and delapril hydrochloride, were evaluated in 20 hypertensive patients
      with a history of cerebral infarction. Each agent was administered orally each
      day for 12 weeks using an open randomized crossover design. After 4 weeks'
      treatment, 75 mg/kg captopril significantly (P less than 0.01) increased platelet
      angiotensin II concentrations and the increase was maintained for a further 8
      weeks. Treatment with 5 mg/day enalapril resulted in no significant change in
      angiotensin II. Treatment with 30 mg/day delapril hydrochloride significantly (P
      less than 0.05) decreased platelet angiotensin II concentrations at 4 weeks and
      the change persisted for 12 weeks (P less than 0.01). During delapril
      hydrochloride treatment platelet angiotensin II concentrations approached normal
      values. It is concluded that delapril hydrochloride may be used to treat patients
      with arteriosclerosis disorders and may inhibit the tendency for atherosclerotic
      changes and thrombosis.

PMID- 1397675
TI  - Combined zidovudine and interferon-alpha 2a therapy in children with acquired
      immune deficiency syndrome.
AB  - A study was carried out in five children with acquired immune deficiency syndrome
      to assess the effect of combined zidovudine/interferon-alpha 2a therapy with that
      of zidovudine given alone on immunological profiles and plasma zidovudine
      concentrations. Immunoglobulins A, G and M, total and absolute CD4 lymphocyte
      counts, and p24 antigen concentrations did not differ significantly when children
      were treated with 300 mg/m2 zidovudine given orally once every 12 h, or with 150
      mg/m2 zidovudine plus 1.5 or 3 MIU interferon-alpha 2a given intramuscularly
      three times weekly. Peak plasma zidovudine concentrations were significantly (P
      less than 0.05) lower when combined treatment with 150 mg/m2 zidovudine/1.5 MIU
      interferon-alpha 2a was administered compared with 300 mg/m2 zidovudine alone, or
      combined 150 mg/m2 zidovudine/3 MIU interferon-alpha 2a. The results suggest that
      combination zidovudine/interferon-alpha 2a therapy may be more efficacious than
      zidovudine alone and that the normal zidovudine dose may be reduced if interferon
      alpha 2a is given in addition, thus reducing the side-effects associated with
      zidovudine.

PMID- 1397676
TI  - Phenotypic changes of human smooth muscle cells during development: late
      expression of heavy caldesmon and calponin.
AB  - Expression of the regulatory contractile proteins, heavy caldesmon (h-caldesmon)
      and calponin was studied in human aortic smooth muscle cells (SMCs) during
      development and compared with the expression of alpha-SM-actin and smooth muscle
      myosin heavy chain (SM-MHCs). For this study, novel monoclonal antibodies
      specific to SM-MHCs, h-caldesmon, and calponin were developed and characterized.
      Aortic SMCs from fetuses of 8-10 and 20-22 weeks of gestation express alpha-SM
      actin and SM-MHCs, but neither h-caldesmon nor calponin were expressed as
      demonstrated by immunoblotting and immunofluorescence techniques. In the adult
      aortic tunica media, SMCs contain all four markers. Thus, the expression of
      calponin, similar to the expression of alpha-SM-actin, SM-MHCs, and h-caldesmon,
      is developmentally regulated in aortic SMCs. In the adult aortic subendothelial
      (preluminal) part of tunica intima, numerous cells containing SM-MHCs, but
      lacking h-caldesmon and calponin, were found. These results illustrate the
      similarity of SMCs from intimal thickenings and immature (fetal) SMCs. Expression
      of contractile proteins in the developing SMCs is coordinately regulated;
      however, distinct groups of proteins appear to exist whose expression is
      regulated differently. Actin and myosin, being major contractile proteins, also
      play a structural role and appear rather early in development, whereas caldesmon
      and calponin, being involved in regulation of contraction, can serve as markers
      of higher SMC differentiation steps. In contrast, h-caldesmon and calponin were
      already present in visceral SMCs (trachea, esophagus) of the 10-week-old fetus.
      These results demonstrate that the time course of maturation of visceral SMCs is
      different from that of vascular SMCs.

PMID- 1397677
TI  - Factors necessary for restoring an evolutionary change in an anural ascidian
      embryo.
AB  - The ascidian Molgula oculata has a tailed (or urodele) larva, whereas Molgula
      occulta develops directly via a tailless (or anural) embryo. Interspecific hybrid
      embryos produced by fertilizing M. occulta eggs with M. oculata sperm (M. occulta
      x M. oculata hybrids) can develop urodele larval structures, including a brain
      pigment cell and a short tail containing a small notochord. Development of larval
      features differs in individual M. occulta clutches: some eggs develop into
      hybrids with both a brain pigment cell and a tail, some into hybrids with either
      a brain pigment cell or a tail, and others into hybrids without urodele features.
      The expression of a 58-kDa protein (p58), which is present in eggs and embryos of
      urodele ascidians but lacking in those of most anural species, also varies in
      expression between different clutches of M. occulta eggs. Western blot and
      immunofluorescence studies show that p58 expression is correlated with the
      ability of hybrid embryos to express urodele features. For example, clutches of
      M. occulta eggs containing relatively high levels of p58 produce many hybrids
      with both a brain pigment cell and a tail. Differential expression of p58 occurs
      during oogenesis in M. occulta individuals: p58 is found at similar levels in
      previtellogenic oocytes, but in some animals it disappears during vitellogenesis,
      while in others it persists throughout oogenesis and is present in mature eggs.
      When M. occulta eggs are extracted with Triton X-100, p58 remains in the
      detergent-insoluble fraction, suggesting that it is associated with the
      cytoskeleton. In most unfertilized M. occulta eggs, p58 is uniformly distributed,
      but after fertilization it is localized in the uncleaved zygote and then
      concentrated in embryonic ectoderm, notochord, and muscle lineage cells. Despite
      containing high levels of p58, gynogenetic hybrid embryos, produced by
      fertilizing M. occulta eggs with uv-irradiated M. oculata sperm, develop into
      hybrids without a brain pigment cell or a tail. The results suggest that both a
      functional paternal genome and p58 are necessary for restoration of larval
      features in M. occulta x M. oculata hybrids. The cytoskeletal complex containing
      p58 may mediate the localization of key maternal factors in the egg or may be
      involved in cellular interactions during embryogenesis which are responsible for
      development of urodele cell fates.

PMID- 1397678
TI  - Skeletal muscle satellite cells appear during late chicken embryogenesis.
AB  - The emergence of avian satellite cells during development has been studied using
      markers that distinguish adult from fetal cells. Previous studies by us have
      shown that myogenic cultures from fetal (Embryonic Day 10) and adult 12-16 weeks)
      chicken pectoralis muscle (PM) each regulate expression of the embryonic isoform
      of fast myosin heavy chain (MHC) differently. In fetal cultures, embryonic MHC is
      coexpressed with a ventricular MHC in both myocytes (differentiated myoblasts)
      and myotubes. In contrast, myocytes and newly formed myotubes in adult cultures
      express ventricular but not embryonic MHC. In the current study, the appearance
      of myocytes and myotubes which express ventricular but not embryonic MHC was used
      to determine when adult myoblasts first emerge during avian development. By
      examining patterns of MHC expression in mass and clonal cultures prepared from
      embryonic and posthatch chicken skeletal muscle using double-label
      immunofluorescence with isoform-specific monoclonal antibodies, we show that a
      significant number of myocytes and myotubes which stain for ventricular but not
      embryonic MHC are first seen in cultures derived from PM during fetal development
      (Embryonic Day 18) and comprise the majority, if not all, of the myoblasts
      present at hatching and beyond. These results suggest that adult type myoblasts
      become dominant in late embryogenesis. We also show that satellite cell cultures
      derived from adult slow muscle give results similar to those of cultures derived
      from adult fast muscle. Cultures derived from Embryonic Day 10 hindlimb form
      myocytes and myotubes that coexpress ventricular and embryonic MHCs in a manner
      similar to cells of the Embryonic Day 10 PM. Thus, adult and fetal expression
      patterns of ventricular and embryonic MHCs are correlated with developmental age
      but not muscle fiber type.

PMID- 1397679
TI  - Temporal appearance of satellite cells during myogenesis.
AB  - In this study, differences between fetal and adult myoblasts in clonal and high
      density culture have been used to determine when adult myoblasts can first be
      detected during avian development. The results indicate that avian adult
      myoblasts are apparent as a distinct population of myoblasts during the midfetal
      stage of development. Three different criteria were used to differentiate fetal
      and adult myoblasts and demonstrate when adult myoblasts become a major
      proportion of the myoblast population: (1) differences in slow myosin heavy chain
      1 (MHC1) isoform expression, (2) initiation of DNA synthetic activity, and (3)
      average myoblast length. Fetal chicken (ED10-12) pectoralis muscle (PM) myoblasts
      form myotubes that express slow MHC1 after prolonged culture, while adult chicken
      PM myoblasts do not. Fetal avian myoblasts were active in DNA synthesis and large
      when first isolated, reaching peak rates of synthesis by 24 hr in culture, while
      adult myoblasts were inactive in DNA synthesis and small when first isolated,
      only reaching peak rates of DNA synthesis and size at 3 days of incubation. A
      dramatic decrease in the percentage of muscle colonies with fibers that expressed
      slow MHC1 was observed between the midfetal stage and hatching in the chicken,
      along with a corresponding decrease in myoblast DNA synthetic activity and
      average length during this same period in both the chicken and the quail.
      Myoblast activity and average length increased again 3-4 days posthatch and a
      small transient increase in the number of slow MHC1-expressing clones was also
      associated with the massive growth of muscle that occurs in the neonatal bird. We
      conclude that adult myoblasts are present as a distinct population of myoblasts
      at least as early as the midfetal stages of avian development.

PMID- 1397680
TI  - The fertilization potential and associated membrane potential oscillations during
      the resumption of meiosis in the egg of the ascidian Phallusia mammillata.
AB  - The fertilization potential in Phallusia mammillata consisted of an initial rapid
      depolarization. This initial sperm-triggered depolarization was followed by a
      phase of membrane depolarization which was of either long or short duration,
      depending on the eggs. When of long duration, the phase of membrane
      depolarization was divided into two periods: the first one began with a plateau
      (Em = +20.2 +/- 1.1 mV; duration = 1.7 +/- 0.14 min) which was followed by a
      series of membrane potential oscillations (n = 3.1 +/- 0.25) lasting 2.4 +/- 0.2
      min. The second period also began as a plateau (Em = approximately 0 mV; duration
      = 3.40 +/- 0.20 min) which was followed by a series of oscillations (n = 11.5 +/-
      0.5) lasting 11.8 +/- 0.6 min, followed by a membrane repolarization. The second
      series of oscillations often continued rising from the resting potential value.
      In the eggs displaying a short duration of membrane depolarization, the second
      period of depolarization was shortened (lasting only 3.5 +/- 0.5 min) since it
      lacked the second plateau. In addition it displayed a smaller number of
      oscillations (n = 4.7 +/- 0.6). As a consequence of this shortening, the membrane
      repolarized sooner. After repolarization, the membrane displayed several
      potential oscillations that started from the repolarization level. Regardless of
      the length of the depolarized plateau phases, the total number of membrane
      oscillations and the time period during which they occurred were constant. Eggs
      displaying a long depolarization phase had 15.9 +/- 0.6 oscillations in a 19.5 +/
      0.6 min interval, while eggs having a short depolarization phase had 16.0 +/-
      0.8 oscillations in a 18.1 +/- 0.3 min interval. The time period during which the
      potential oscillations occurred corresponded remarkably well with the time of the
      meiotic divisions: the formation of the first polar body was detected about 80
      sec after the end of the first series of oscillations; the second polar body was
      extruded about 85 sec after the last membrane oscillation occurred.

PMID- 1397681
TI  - Differentiation of retinal precursor cells born in vitro.
AB  - It is not known whether the differentiated fate of retinal precursor cells is
      determined before, during, or after terminal mitosis. Previous studies from this
      laboratory led to the hypothesis that retinal precursor cells remain plastic
      after final mitosis and will follow a photoreceptor "default pathway" unless
      induced to develop as neurons by intraretinal factors. This hypothesis predicts
      that isolated precursors undergoing terminal mitosis and differentiation in cell
      culture, in the absence of the retinal microenvironment, should become
      photoreceptors, regardless of embryonic age. To test this prediction precursor
      cells were dissociated from 5- to 8-day chick embryo retinas and grown as single
      cells in vitro. Bromodeoxyuridine (BRDU)- and [3H]thymidine-labeling techniques,
      coupled with serial photography of precursor development in culture, showed that
      at all donor ages some of the isolated cells divided one or more times and became
      postmitotic in vitro. Analysis of cell phenotype by phase-contrast microscopy,
      sequential photography, autoradiography, and immunocytochemistry showed that the
      majority of precursors from all donor ages differentiated as photoreceptors.
      These observations support a prediction derived from the "photoreceptor default"
      hypothesis.

PMID- 1397682
TI  - Isolation of cDNAs for LCE and HCE, two constituent proteases of the hatching
      enzyme of Oryzias latipes, and concurrent expression of their mRNAs during
      development.
AB  - The hatching enzyme of medaka consists of two types of proteases (HCE, LCE). cDNA
      clones for LCE and HCE were isolated from a lambda gt11 cDNA library constructed
      with poly(A)+ RNA of Day 3 embryos. LCE cDNA is 936 bp long and contains an 813
      bp open reading frame encoding a preproenzyme with a 20-amino-acid signal
      sequence, a 51-amino-acid propeptide, and a 200-amino-acid mature enzyme. For
      HCE, two distinct cDNAs (HCE21, HCE23) having nucleotide sequences with 92.8%
      similarity were obtained. These cDNAs contain open reading frames encoding
      preproenzymes of 279 and 270 amino acids, respectively. The mature enzyme forms
      of both consist of 200 amino acids, the similarity between them being 95.5%. On
      Northern blotting analysis, the transcripts of LCE and HCE genes were first
      detected coincidentally in Day 2 embryos shortly before the production of LCE and
      HCE, accumulated thereafter in parallel, and dramatically decreased after
      hatching. The amino acid sequence, the HExxH motif, which is known to constitute
      an active site in some Zn proteases, is also found in LCE and HCE. However, the
      sequence analyses strongly suggest that both the enzymes belong to the astacin
      (protease) family, being distinct from sea urchin hatching enzyme, which is
      reportedly similar to collagenase.

PMID- 1397684
TI  - Changes in voltage-dependent ion currents during meiosis and first mitosis in
      eggs of an ascidian.
AB  - Different patterns of voltage-dependent ion currents are present in mature eggs
      and in early embryos of the ascidian Boltenia villosa, as if each ion current is
      regulated in a different manner between fertilization and the early cleavages of
      embryogenesis. The ion currents appear and/or disappear with precise timing
      suggesting that they play important roles at specific times during early
      development. We investigated changes in three voltage-dependent ion currents (an
      inwardly rectifying chloride current, a calcium current, and a sodium current)
      and membrane surface area over time between the resumption of meiosis (with
      fertilization or activation) and the first mitotic cleavage. Using time-lapse
      video recordings made during whole-cell patch-clamp experiments, we were able to
      correlate electrophysiological changes with morphological changes and cell cycle
      related events. Between fertilization and first cleavage, INa was lost
      exponentially, the density of ICa remained relatively constant, and the
      amplitudes of both ICl and membrane surface area fluctuated in time with the cell
      cycle. ICl and surface area increased whenever the cell began dividing--with the
      polar body extrusions and the formation of the first cleavage furrow. This
      suggested that the values of ICl and surface area were largest during interphase
      and smallest during M-phase of each cell cycle. This hypothesis was supported by
      an experiment in which entry into M-phase was blocked in fertilized eggs by
      inhibiting protein synthesis. This prevented the decreases of ICl and surface
      area but allowed the increases to occur normally. Patterns of change in ion
      currents are current specific and, as is the case with ICl, are tightly
      correlated with developmental events.

PMID- 1397683
TI  - The repetitive calcium waves in the fertilized ascidian egg are initiated near
      the vegetal pole by a cortical pacemaker.
AB  - Ascidian eggs respond to fertilization with a series of repetitive calcium waves
      that originate mostly from the vegetal/contraction pole region (J. E.
      Speksnijder, C. Sardet, and L. F. Jaffe, 1990, Dev. Biol. 142, 246-249), where
      the myoplasm is concentrated during the first phase of ooplasmic segregation.
      This suggests that the myoplasm may be involved in initiating these calcium
      waves. To test this possibility, the starting position of the calcium waves was
      determined in eggs that had the subcortical, mitochondria-rich part of the
      myoplasm displaced by centrifugation. Such centrifuged eggs display four
      cytoplasmic layers: a large centrifugal yolk zone, a narrow clear zone, a
      mitochondria-rich layer, and a small clear zone at the centripetal pole. Imaging
      of the cytosolic calcium in centrifuged eggs that were injected with the calcium
      specific photoprotein aequorin reveals a series of repetitive calcium waves after
      fertilization. About 70% of these waves start in the vegetal/contraction pole
      area, which is similar to the number of waves previously found to start in this
      area in uncentrifuged eggs. In contrast, only about 25% of the waves start close
      to the displaced mitochondria-rich layer. From this result it is concluded that
      the main wave initiation site is not displaced by the centrifugal forces that
      displace the subcortical, mitochondria-rich part of the myoplasm. Moreover, the
      observation that the animal-vegetal polarity of cortical components such as actin
      filaments and the endoplasmic reticulum has been retained after centrifugation
      further suggests that a cortical component located in the vegetal hemisphere-
      most likely the endoplasmic reticulum network in the cortical region of the
      myoplasm--is involved in initiating the repetitive calcium waves in the
      fertilized ascidian egg.

PMID- 1397685
TI  - Maturation-specific deadenylation in Xenopus oocytes requires nuclear and
      cytoplasmic factors.
AB  - During the meiotic maturation of Xenopus oocytes, maternal mRNAs that lack a
      cytoplasmic polyadenylation element are deadenylated and translationally
      inactivated. In this report, we have characterized the regulation of poly(A)
      removal during maturation. Deadenylation in vivo is detected only after germinal
      vesicle breakdown and does not require de novo protein synthesis. Enucleated
      oocytes do not deadenylate either endogenous or microinjected RNAs upon
      maturation, indicating that a nuclear component is required for poly(A) removal.
      Whole cell extracts prepared from both immature and mature oocytes deadenylate
      exogenous RNA substrates in vitro. Deadenylation activity is not detected in
      isolated nuclear or cytoplasmic extracts obtained from immature oocytes, but is
      reconstituted when these fractions are combined in vitro. These results indicate
      that the factors required for deadenylation activity are present in immature
      oocytes, but that poly(A) removal is prevented by the sequestration of one or
      more of these components within the nucleus. Maturation-specific deadenylation of
      maternal mRNAs occurs upon the release of nuclear factors into the cytoplasm at
      germinal vesicle breakdown.

PMID- 1397686
TI  - Effects of antibodies against N-cadherin and N-CAM on the cranial neural crest
      and neural tube.
AB  - We have examined the distribution and function of the defined cell adhesion
      molecules, N-cadherin and N-CAM, in the emigration of cranial neural crest cells
      from the neural tube in vivo. By immunocytochemical analysis, both N-cadherin and
      N-CAM were detected on the cranial neural folds prior to neural tube closure.
      After closure of the neural tube, presumptive cranial neural crest cells within
      the dorsal aspect of the neural tube had bright N-CAM and weak N-cadherin
      immunoreactivity. By the 10- to 11-somite stage, N-cadherin was prominent on all
      neural tube cells with the exception of the dorsal-most cells, which had little
      or no detectable immunoreactivity. N-CAM, but not N-cadherin, was observed on
      some migrating neural crest cells after their departure from the cranial neural
      tube. To examine the functional significance of these molecules, perturbation
      experiments were performed by injecting antibodies against N-CAM or N-cadherin
      into the cranial mesenchyme adjacent to the midbrain. Fab' fragments or whole
      IgGs of monoclonal and polyclonal antibodies against N-CAM caused abnormalities
      in the cranial neural tube and neural crest. Predominantly observed defects
      included neural crest cells in ectopic locations, both within and external to the
      neural tube, and mildly deformed neural tubes containing some dissociating cells.
      A monoclonal antibody against N-cadherin also disrupted cranial development, with
      the major defect being grossly distorted neural tubes and some ectopic neural
      crest cells outside of the neural tube. In contrast, nonblocking N-CAM antibodies
      and control IgGs had few effects. Embryos appeared to be sensitive to the N-CAM
      and N-cadherin antibodies for a limited developmental period from the neural fold
      to the 9-somite stage, with older embryos no longer displaying defects after
      antibody injection. These results suggest that the cell adhesion molecules N-CAM
      and N-cadherin are important for the normal integrity of the cranial neural tube
      and for the emigration of neural crest cells. Because cell-matrix interactions
      also are required for proper emigration of cranial neural crest cells, the
      results suggest that the balance between cell-cell and cell-matrix adhesion may
      be critical for this process.

PMID- 1397687
TI  - Spatial and temporal transcellular current patterns during oogenesis.
AB  - We have used the two-dimensional vibrating probe to examine spatial and temporal
      patterns in the transcellular current flow around telotrophic ovarioles of the
      insect Rhodnius prolixus. We demonstrate a dynamic pattern of currents which
      correlates with various stages of vitellogenesis. Asymmetries exist in the radial
      current pattern around intact ovarioles, particularly around the terminal
      follicle, and may correlate with early developmental axes. The extra-cellular
      current pattern is largely reflected by a similar, though weaker pattern of
      currents over the germ cell membranes, indicating that both germ cell and somatic
      cell membranes are involved in current generation. Current enters previtellogenic
      oocytes and leaves oocytes entering vitellogenesis. We speculate that current
      reversal and loss of trophic cord contact may represent an electrophysiological
      feedback control mechanism during oogenesis.

PMID- 1397688
TI  - Exogenous transferrin is taken up and localized by the neurulation-stage mouse
      embryo in vitro.
AB  - We have screened neurulation-stage mouse embryos for regional differences in
      protein distribution, by two-dimensional sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. The screen has revealed an 83-kD protein (pI 6.8) that is
      present in embryo regions where neurulation is in progress but not in regions
      where neurulation is complete. The 83-kD protein is not synthesized in the
      neurulation-stage embryo or in the yolk sac, but is taken up from the culture
      serum in vitro and, probably, from the maternal serum in utero. The 83-kD protein
      has been identified as transferrin on the basis of its electrophoretic migration
      and recognition on Western blots by an antitransferrin antibody. Culture of
      embryos in serum containing 125I-transferrin, followed by autoradiography of
      embryo sections, shows that transferrin is taken up and localized in the gut
      beneath the closing neural folds at several levels of the body axis in 8.5- and
      9.5-day embryos. In situ hybridization studies show that the transferrin receptor
      mRNA is expressed in all cells of the 9.5-day embryo, including the gut endoderm.
      These findings are consistent with a role for transferrin in development of the
      gut and perhaps, indirectly, in completion of neurulation during early mouse
      embryogenesis.

PMID- 1397689
TI  - Transforming growth factor beta 1 is an epithelial-derived signal peptide that
      influences otic capsule formation.
AB  - Interactions between epithelial and mesenchymal tissues in the developing inner
      ear direct the formation of its cartilaginous capsule. Recent work indicates that
      many growth factors are distributed in the early embryo in vivo in a temporal
      spatial pattern that correlates with sites of ongoing morphogenetic events. We
      report here that the localization of transforming growth factor beta 1 (TGF-beta
      1) in both epithelial and mesenchymal tissues of the mouse inner ear between 10
      and 16 days of embryonic development (E10-E16). In addition, utilizing a high
      density culture system as an in vitro model of otic capsule chondrogenesis, we
      show that modulation of chondrogenesis by TGF-beta 1 in cultured mouse periotic
      mesenchyme mimics the in vitro effects of otic epithelium on the expression of
      chondrogenic potential. We provide evidence of a causal relationship of this
      growth factor to otic capsule formation in situ by demonstrating that the actual
      sequence of chondrogenic events that occur in the developing embryo is reproduced
      in culture by the addition of exogenous TGF-beta 1 peptide. Furthermore, in
      cultures of mesenchyme containing otic epithelium, we demonstrate the
      localization of endogenous TGF-beta 1, first within the epithelial tissue and
      later within both the epithelium and its surrounding periotic mesenchyme,
      contrasted to an absence of endogenous TGF-beta 1 in cultures of mesenchyme
      alone. Our results suggest that TGF-beta 1 is one of the signal molecules that
      mediate the effects of otic epithelium in influencing the formation of the
      cartilaginous otic capsule.

PMID- 1397690
TI  - The armadillo homologs beta-catenin and plakoglobin are differentially expressed
      during early development of Xenopus laevis.
AB  - Plakoglobin and beta-catenin are cytoplasmic proteins associated with the
      intracellular plaques of cell adhesive junctions. While plakoglobin is present in
      both adherens junctions and desmosomes, beta-catenin is associated with the
      cadherins that accumulate only in adherens junctions. Both beta-catenin and
      plakoglobin are homologs of armadillo, a Drosophila segment polarity gene that is
      considered to be in the wingless signaling pathway. We have characterized the
      expression and distribution of both plakoglobin and beta-catenin in Xenopus
      embryos. As shown by RNA blot analysis, beta-catenin and plakoglobin transcripts
      are present in fertilized eggs and in embryos through to tadpole stage. Whole
      mount in situ hybridization indicates that both genes are expressed in the dorsal
      ectoderm and mesoderm of tailbud- and tadpole-stage embryos and that beta-catenin
      is expressed in the midbrain. Both plakoglobin and beta-catenin polypeptides are
      present during early Xenopus development; however, differences exist in the
      timing of maximal expression. Plakoglobin is present in the fertilized egg,
      increases in abundance by neurula stage, then declines at the tailbud and tadpole
      stages. beta-Catenin, recognized by an anti-arm antibody, is also present in the
      fertilized egg and in blastula-stage embryos. However, beta-catenin continues to
      be detected at the neurula, tailbud, and tadpole stages when levels of
      plakoglobin decline. The presence of multiple homologs of armadillo in Xenopus
      embryos and the differences in their patterns of expression suggest distinct
      roles for these proteins in processes affected by cell adhesion.

PMID- 1397691
TI  - Expression of a mouse zinc finger protein gene in both spermatocytes and oocytes
      during meiosis.
AB  - In order to identify genes regulating meiosis, a mouse spermatocyte cDNA library
      was screened for sequences encoding proteins with C2H2-type zinc finger motifs
      which are typically expressed by the Drosophila Kruppel gene. Three new cDNAs
      were isolated, and they were designated CTfin33, CTfin51, and CTfin92. Among
      them, CTfin51 was selected for further study. The deduced amino acid sequence
      revealed seven zinc finger motifs in its C-terminal region. Northern blot and in
      situ hybridization showed CTfin51 mRNA expression in spermatocytes after the
      pachytene stage and in early stage round spermatids of prepuberal and adult
      males. Immunocytochemical staining with an antiserum against beta-gal-CTfin51
      fusion protein was localized within nuclei of spermatocytes and spermatids.
      Oocyte nuclei after the pachytene stage also were immunoreactive for CTfin51
      protein. Immunoblots revealed a band at M(r) 75,000 in protein extracts from the
      testis and the ovary. These results suggest that the CTfin51 gene encodes a DNA
      binding regulatory protein functionally associated with meiosis in both male and
      female gametogenesis.

PMID- 1397692
TI  - Altered morphology in transgenic tobacco plants that overproduce cytokinins in
      specific tissues and organs.
AB  - An auxin-inducible bidirectional promoter from the soybean SAUR gene locus was
      fused to a reporter gene in one direction and a cytokinin biosynthetic gene in
      the opposite direction and the expression of these fused genes was examined in
      transgenic tobacco. The Escherichia coli uidA gene, which encodes the enzyme beta
      glucuronidase (GUS), was used as the reporter gene and the Agrobacterium
      tumefaciens ipt gene, which encodes the enzyme isopentenyl transferase, was used
      as the cytokinin biosynthetic gene. These constructs allowed the overproduction
      of cytokinins in tobacco in a tissue- and organ-specific manner. Localized
      overproduction of cytokinins was monitored using the GUS reporter gene and
      measured by an ELISA assay. The tissue- and organ-specific overproduction of
      cytokinins produced a number of morphological and physiological changes,
      including stunting, loss of apical dominance, reduction in root initiation and
      growth, either acceleration or prolonged delayed senescence in leaves depending
      on the growth conditions, adventitious shoot formation from unwounded leaf veins
      and petioles, altered nutrient distribution, and abnormal tissue development in
      stems. While some of these morphological changes result directly from the
      localized overproduction of cytokinins, other changes probably result from the
      mobilization of plant nutrients to tissues rich in cytokinins.

PMID- 1397693
TI  - Histone H2A.F/Z mRNA is stored in the egg cytoplasm and basally regulated in the
      sea urchin embryo.
AB  - The sea urchin H2A.F/Z histone is a member of a subclass of highly conserved H2A
      variants. Sequence analysis confirms that H2A.F/Z mRNA is polyadenylated. In situ
      hybridization studies demonstrate that maternal H2A.F/Z message is stored in the
      egg cytoplasm and present at equal levels in all cells of the mesenchyme blastula
      stage embryo, suggesting that H2A.F/Z is not coordinately regulated with DNA
      synthesis. When blastula-stage embryos were exposed to DNA synthesis inhibitors,
      no effect on the steady-state level of H2A.F/Z mRNA was observed, while the level
      of late class H2B mRNA decreased substantially. These results provide evidence
      that the basal mode of regulation of this unusual histone variant is conserved
      evolutionarily.

PMID- 1397694
TI  - Myb p75 oncoprotein is expressed in developing otic and epibranchial placodes.
AB  - The c-myb proto-oncogene encodes a transcriptional regulatory protein which is
      highly conserved throughout evolution. Myb has been considered to be normally
      restricted to hematopoietic tissues, but there are indications that this might
      not always be the case. The present work shows the expression of a p75 Myb
      oncoprotein in the otic vesicle and epibranchial placodes of the early chick
      embryo. Expression was sequential and followed the same time course as the
      formation of placode-derived cranial ganglia. The results suggest a potential
      role for c-myb in regulation of placode development and neurogenesis.

PMID- 1397695
TI  - Membrane-associated neurotransmitter stimulating factor is very similar to
      ciliary neurotrophic factor.
AB  - Membrane-associated neurotransmitter stimulating factor (MANS) can modulate
      sympathetic neurotransmitter expression and promote ciliary neuron survival in
      cell culture. Previous studies have shown that its biological effects and
      biochemical properties are similar to those of ciliary neurotrophic factor
      (CNTF). In addition, CNTF is present in spinal cord, the source of MANS. These
      observations raised the possibility that MANS preparations contain CNTF. We find
      that partially purified MANS fractions contain a 24-kD protein that is recognized
      in Western blots by an antiserum generated against recombinant rat CNTF (rCNTF).
      This antiserum immunoprecipitates virtually all the cholinergic-inducing and the
      ciliary neurotrophic activities present in MANS preparations. When iodinated
      rCNTF is incubated with spinal cord membranes, a significant proportion of the
      labeled CNTF segregates with the membrane pellet. The membrane-associated
      exogenous CNTF can be eluted from the membrane fraction by treatment with high
      salt solutions, similar to that used to solubilize MANS from spinal cord
      membranes. Our data suggest that a substantial portion of the cholinergic
      differentiation and ciliary neurotrophic activities present in MANS preparations
      can be attributed to CNTF or a CNTF-like molecule.

PMID- 1397696
TI  - Electrophysiology of stimulus-secretion coupling in human beta-cells.
AB  - Herein, we review the applicability to human beta-cells of an
      electrophysiologically based hypothesis of the coupling of glucose metabolism to
      insulin secretion. According to this hypothesis, glucose metabolism leads to the
      generation of intracellular intermediates (including ATP), which leads to closure
      of ATP-sensitive K+ channels. Channel closure results in membrane depolarization,
      the onset of electrical activity, and voltage-dependent Ca2+ entry. The resultant
      rise in cytosolic Ca2+ leads to Ca(2+)-dependent exocytosis of insulin granules.
      We found that most of the published experimental evidence for human beta-cells
      supports this hypothesis. In addition, we present three other emerging lines of
      evidence in support of this hypothesis for human islet beta-cells: 1) the effects
      of pHi-altering maneuvers on insulin secretion and electrical activity; 2)
      preliminary identification of LVA and HVA single Ca2+ channel currents; and 3)
      validation of the feasibility of Cm measurements to track insulin granule
      exocytosis. On the basis of this last new line of evidence, we suggest that
      combinations of Cm measurements and electrical activity/membrane current
      measurements may help define the roles of diverse electrical activity patterns,
      displayed by human beta-cells, in stimulus-induced insulin secretion.

PMID- 1397697
TI  - Insulin is required for the liver to respond to intraportal glucose delivery in
      the conscious dog.
AB  - To determine whether insulin is essential for the augmented hepatic glucose
      uptake observed in the presence of intraportal glucose delivery, SRIF was used to
      induce acute insulin deficiency in 5 conscious dogs, and glucose was infused into
      the portal vein or a peripheral vein in two sequential, randomized periods.
      Insulin and C-peptide levels were below the limits of detection after SRIF
      infusion, and the load of glucose presented to the liver was approximately
      doubled and equivalent during the portal and peripheral periods. Net hepatic
      glucose output was 2.9 +/- 0.9 and 2.1 +/- 1.1 mumol.kg-1.min-1 during portal and
      peripheral glucose delivery, respectively. In an additional set of protocols,
      pancreatectomized dogs were used to investigate the effects of prolonged insulin
      deficiency (n = 5) and acute insulin replacement (n = 4) on the hepatic response
      to intraportal glucose delivery. In the prolonged insulin deficiency protocol,
      SRIF was used to lower glucagon and thereby reduce circulating glucose levels,
      and glucose was infused into the portal or peripheral circulations in two
      sequential, randomized periods. As with acute insulin deficiency, net hepatic
      glucose output was still evident and similar (3.6 +/- 1.1 and 4.2 +/- 1.3
      mumol.kg-1.min-1) during portal and peripheral glucose delivery, respectively.
      When the pancreatectomized dogs were restudied using a similar protocol, but one
      in which insulin was replaced (4X-basal), and the glucose load to the liver was
      matched to that which occurred in the prolonged insulin deficiency protocol, net
      hepatic glucose uptake was 23.6 +/- 6.1 mumol.kg-1.min-1 during portal glucose
      delivery but only 10.3 +/- 3.5 mumol.kg-1.min-1 during peripheral glucose
      delivery. These results suggest that the induction of net hepatic glucose uptake
      and the augmented hepatic response to intraportal glucose delivery require the
      presence of insulin.

PMID- 1397698
TI  - Evidence for distinctive and intrinsic defects in insulin action in polycystic
      ovary syndrome.
AB  - Women with PCO have a unique but poorly characterized disorder of insulin action.
      Obese (n = 16) and nonobese (n = 14) PCO women and age- and weight-matched
      normal, nondiabetic ovulatory women (obese, n = 15; nonobese, n = 17) had insulin
      action determined in vivo with sequential multiple insulin dose euglycemic clamps
      and in isolated abdominal adipocytes to clarify the mechanisms of insulin
      resistance. PCO resulted in significant increases in the ED50 insulin for glucose
      utilization in vivo (P less than 0.001) and in adipocytes (P less than 0.01),
      without significant changes in adipocyte insulin-binding sites. PCO also resulted
      in significant decreases in maximal insulin-stimulated rates of glucose
      utilization in vivo (P less than 0.01) and in adipocytes (P less than 0.01).
      Obesity resulted in smaller decreases in insulin sensitivity than PCO (ED50
      insulin, P less than 0.001 in vivo and P less than 0.05 in adipocytes), but
      greater decreases in insulin responsiveness (Vmax, P less than 0.001 in vivo and
      in adipocytes). The ED50 insulin for suppression of HGP was increased only in
      obese PCO women (P less than 0.001), and the interactions between PCO and obesity
      on this parameter were statistically significant. No significant correlations
      between androgen or estrogen levels and adipocyte insulin binding or action were
      found. Because insulin binding was not changed, we conclude that the major lesion
      causing insulin resistance in PCO is a striking decrease in insulin sensitivity
      secondary to a defect in the insulin receptor and/or postreceptor signal
      transduction. PCO also is associated with modest but significant decreases in
      glucose transport. These defects in insulin action appear to represent intrinsic
      abnormalities that are independent of obesity, metabolic derangements, body fat
      topography, and sex hormone levels. Conversely, changes in hepatic insulin
      sensitivity appear to be acquired with obesity.

PMID- 1397699
TI  - Lp(a) concentrations in NIDDM.
AB  - NIDDM patients have a two- to fourfold increased risk of CHD relative to
      nondiabetic subjects. This excess risk is explained only partially by increased
      levels of standard risk factors. We compared the plasma concentrations of Lp(a)
      in NIDDM patients (n = 260) and nondiabetic subjects (n = 336) who participated
      in a population-based study (San Antonio Heart Study). Lp(a) was measured using a
      monoclonal anti-Lp(a) antibody. NIDDM patients and nondiabetic subjects had
      similar Lp(a) concentrations for both men (13.6 +/- 1.5 vs. 16.1 +/- 1.4 mg/dl)
      and women (12.6 +/- 0.8 vs. 15.9 +/- 1.3 mg/dl) (P = 0.361). Duration of diabetes
      and level of fasting glycemia were not significantly related to Lp(a)
      concentrations. Lp(a) levels were significantly higher in patients who had higher
      total and LDL cholesterol levels. We conclude that in a large population-based
      study, Lp(a) levels are not increased in NIDDM patients.

PMID- 1397700
TI  - Prevention of adoptive transfer in BB rats by prophylactic insulin treatment.
AB  - Prophylactic insulin can prevent diabetes in the BB rat. We evaluated its use to
      prevent adoptive transfer of diabetes by activated splenocytes. ConA-activated
      spleen cells from acutely diabetic BB rats were divided into two equal aliquots
      and injected intravenously in paired diabetes-prone BB rat littermates. At the
      time of cell injection, subcutaneous insulin injections (15 U.kg-1.day-1) were
      started in one of each pair (n = 21) of littermates, and the control littermates
      (n = 21) were injected with saline. The incidence of diabetes, observed 35 days
      after cell injection, was 95% in control rats compared with 29% in insulin
      treated rats (P less than 0.05). To confirm the absence of diabetes, insulin was
      stopped in all nondiabetic insulin-treated rats at 63 days of age. An OGTT was
      performed at 65 days of age: 4 rats were glucose intolerant. All rats received
      comparable numbers of ConA-activated splenocytes. At the time the rats were
      killed, 3 insulin-treated rats had a completely normal morphology and a normal
      glucose tolerance. All control rats had insulitis whether they were diabetic or
      not. No significant difference in any mononuclear subset was observed in relation
      to insulin treatment. We conclude that prophylactic insulin can prevent adoptive
      transfer of diabetes in the BB rat without inducing changes in the mononuclear
      cell subsets.

PMID- 1397701
TI  - Comparison of effects of high and low carbohydrate diets on plasma lipoproteins
      and insulin sensitivity in patients with mild NIDDM.
AB  - Previous studies indicate that diets rich in digestible carbohydrates improve
      glucose tolerance in nondiabetic individuals, but may worsen glycemic control in
      NIDDM patients with moderately severe hyperglycemia. The effects of such high
      carbohydrate diets on glucose metabolism in patients with mild NIDDM have not
      been studied adequately. This study compares responses to an isocaloric high
      carbohydrate diet (60% of total energy from carbohydrates) and a low-carbohydrate
      diet (35% of total energy from carbohydrates) in 8 men with mild NIDDM. Both
      diets were low in saturated fatty acids, whereas the low-carbohydrate diet was
      rich in monounsaturated fatty acids. The two diets were matched for dietary fiber
      content (25 g/day). All patients were randomly assigned to receive first one and
      then the other diet, each for a period of 21 days, in a metabolic ward. Compared
      with the low-carbohydrate diet, the high-carbohydrate diet caused a 27.5%
      increase in plasma triglycerides and a similar increase in VLDL-cholesterol
      levels; it also reduced levels of HDL cholesterol by 11%. Plasma glucose and
      insulin responses to identical standard breakfast meals were studied on days 4
      and 21 of each period, and these did not differ significantly between the two
      diets. At the end of each period, a euglycemic hyperinsulinemic glucose clamp
      study with simultaneous infusion of [3-3H]glucose revealed no significant changes
      in hepatic insulin sensitivity; and peripheral insulin-mediated glucose disposal
      remained unchanged (14.7 +/- 1.4 vs. 16.5 +/- 2.3 microM.kg-1.min-1 on the high
      carbohydrate and low-carbohydrate diets, respectively).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1397702
TI  - Pentosidine formation in skin correlates with severity of complications in
      individuals with long-standing IDDM.
AB  - Pentosidine is an advanced glycosylation end product and protein cross-link that
      results from the reaction of pentoses with proteins. Recent data indicate that
      long-term glycation of proteins with glucose also leads to pentosidine formation
      through sugar fragmentation. In this study, the relationship between the severity
      of diabetic complications and pentosidine formation was investigated in collagen
      from skin-punch biopsies from 25 nondiabetic control subjects and 41 IDDM
      patients with diabetes duration greater than 17 yr. Pentosidine was significantly
      elevated in all IDDM patients versus control subjects (P less than 0.0001). It
      correlated strongly with age (P less than 0.0001) and weakly with duration (P
      less than 0.082). Age-adjusted pentosidine levels were highest in grade 2
      (severe) versus grade 1 and 0 complication in all four parameters tested
      (retinopathy, proteinuria, arterial stiffness, and joint stiffness). Significant
      differences were found for retinopathy (P less than 0.014) and joint stiffness (P
      less than 0.041). The highest degree of association was with the cumulative grade
      of individual complication (P less than 0.005), determined by summing indexes of
      all four parameters. Pentosidine also was significantly elevated in the serum of
      IDDM patients compared with control subjects (P less than 0.0001), but levels
      were not significantly correlated with age, diabetes duration, complication, or
      skin collagen pentosidine (P greater than 0.05). A high correlation between
      pentosidine levels and long-wave collagen-linked fluorescence also was observed,
      suggesting that pentosidine is a generalized marker of accelerated tissue
      modification by the advanced glycosylation/Maillard reaction, which is enhanced
      in IDDM patients with severe complications.

PMID- 1397703
TI  - Heterogeneity of messenger RNA that encodes the rat insulin receptor is limited
      to the domain of exon 11. Analysis by RNA heteroduplex mapping, amplification of
      cDNA, and in vitro translation.
AB  - Structural isoforms of the insulin receptor that occur in various tissues have
      been postulated to be involved in certain actions of insulin in target cells. To
      determine whether these insulin-receptor subtypes are caused by alterations in
      the receptor primary structure, we used RNA heteroduplex mapping and
      amplification of cDNA to detect variation in the coding region of insulin
      receptor mRNA from 5 rat tissues. A complete series of overlapping antisense
      [32P]RNA probes was prepared from plasmids containing segments of a full-length
      rat insulin-receptor cDNA, and probes were hybridized individually in solution
      with polyadenylated RNA from rat brain, kidney, liver, skeletal muscle, and
      spleen. After ribonuclease digestion, probe fragments were analyzed by denaturing
      gel electrophoresis. Tissue-specific cleavage of the mRNA:RNA probe heteroduplex,
      attributable to sequence mismatch, was detected only for a single probe covering
      the distal alpha-subunit, as expected for the known alternative splicing of rat
      insulin-receptor mRNA in this region. No evidence for additional heterogeneity of
      the receptor mRNA coding region was observed in the 5 tissues studied either by
      RNA heteroduplex mapping or, in some areas, by regional amplification of insulin
      receptor cDNA. Cell-free translation of size-fractionated polyadenylated RNA was
      used to further demonstrate that each of the major insulin-receptor mRNA size
      classes in rat liver contained both forms of the alternatively spliced mRNA
      transcripts and produced two insulin-proreceptor polypeptides. These results
      suggest that heterogeneity of the insulin-receptor mRNA coding region affecting
      the receptor primary structure is limited to the distal alpha-subunit near the
      subunit cleavage site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397704
TI  - Influence of glycemic control on interaction of very-low- and low-density
      lipoproteins isolated from type I diabetic patients with human monocyte-derived
      macrophages.
AB  - The VLDL and LDL fractions were isolated from 29 patients with type 1 diabetes at
      the time of admission to the hospital to restore glycemic control and again at
      discharge. These lipoprotein fractions were incubated with human monocyte-derived
      macrophages, and the rates of macrophage CE synthesis were determined. The rates
      of CE synthesis in human macrophages were significantly greater (P less than
      0.005) when incubated with VLDL isolated from type I diabetic patients before
      compared with after glycemic control was attained and averaged 1.84 +/- 0.52 and
      1.09 +/- 0.27 nmol (1.20 +/- 0.34 and 0.71 +/- 0.18 micrograms) [14C]cholesteryl
      oleate synthesized.mg cell protein-1 x 20 h-1, respectively. In contrast, when
      LDL isolated from the same patient during the same period was incubated with
      human macrophages, the rates of cellular cholesteryl ester synthesis did not
      differ significantly and averaged 4.23 +/- 1.26 and 3.91 +/- 0.96 nmol (2.75 +/-
      0.82 and 2.55 +/- 0.63 micrograms) [14C]cholesteryl oleate synthesized.mg-1 cell
      protein.20 h-1, respectively. There was a significant increase in the total
      cholesterol content of VLDL isolated before glycemic control compared with that
      isolated after glycemic control was attained (P less than 0.05) resulting from a
      significant increase in the FC and CE (P less than 0.05) contents of these VLDL
      particles. There was a significant decrease in the ratio of FC to PL in VLDL, but
      not LDL, isolated after glycemic control (P less than 0.05). The percentage of
      apoE in VLDL was significantly decreased (P less than 0.05) after glycemic
      control was attained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397705
TI  - Relationship between decrements in glucose level and metabolic response to
      hypoglycemia in absence of counterregulatory hormones in the conscious dog.
AB  - To determine the relationship between decreases in glucose and metabolic
      regulation in the absence of counterregulatory hormones, we infused overnight
      fasted, conscious, adrenalectomized dogs (lacking cortisol and EPI) with
      somatostatin (to eliminate glucagon and growth hormone) and intraportal insulin
      (30 pmol.kg-1.min-1), creating arterial insulin levels of approximately 2000 pM.
      Glucose was infused during one 120-min period, two 90-min periods, and one 45-min
      period to establish levels of 5.9 +/- 0.1, 3.4 +/- 0.1, 2.5 +/- 0.1, and 1.7 +/-
      0.1 mM, respectively. NE levels were 1.24 +/- 0.23, 1.85 +/- 0.27, 2.04 +/- 0.26,
      and 2.50 +/- 0.20 nM, respectively. During the euglycemic control period, the
      liver took up glucose (7.5 +/- 1.9 mumol.kg-1.min-1), but hypoglycemia triggered
      successively greater rates of net hepatic glucose output (3.0 +/- 0.7, 4.6 +/-
      0.9, and 6.9 +/- 1.4 mumol.kg-1.min-1). Total gluconeogenic precursor uptake by
      the liver increased with hypoglycemia. Intrahepatic gluconeogenic efficiency rose
      progressively (by 106 +/- 42, 199 +/- 56, and 268 +/- 55%). Both glycerol and
      NEFA levels rose, indicating lipolysis was enhanced. Net hepatic NEFA uptake and
      ketone production increased proportionally, but the ketone level rose only with
      severe hypoglycemia. In conclusion, despite marked hyperinsulinemia and the
      absence of glucagon, EPI, and cortisol, we observed that lipolysis and glucose
      and ketone production increase in response to decreases in glucose. This suggests
      that neural and/or autoregulatory mechanisms can play a role in combating
      hypoglycemia.

PMID- 1397706
TI  - Recovery of glucose-induced insulin secretion in a rat model of NIDDM is not
      accompanied by return of the B-cell GLUT2 glucose transporter.
AB  - The NSTZ rat model combines loss of glucose-induced insulin secretion with a
      reduced amount of the high Km B-cell glucose transporter, GLUT2. The purpose of
      this study was to determine whether the restoration of glucose-induced insulin
      secretion was paralleled by an increase of GLUT2. Rats injected at 2 days of age
      with 90 mg/kg STZ were studied at 8-13 wk of age. Insulin secretion was assessed
      in the isolated perfused pancreas with 16.7 mM glucose preceded by 40 min of 0 or
      5.5 mM glucose. In control rats, 16.7 mM glucose caused the same large biphasic
      insulin response whether preceded by 0 or 5.5 mM glucose. In NSTZ rats, after 5.5
      mM glucose, 16.7 mM glucose elicited virtually no rise in insulin release. In
      contrast, after 0 mM glucose, a large insulin response to the glucose challenge
      occurred that was equal to that of the control groups when the differences in B
      cell mass were taken into account. However, the dose-response curve for glucose
      induced insulin secretion was shifted to the left, and no second phase of insulin
      secretion was observed. GLUT2 was assessed after the perfusions by indirect
      immunofluorescence with anti-GLUT2 antisera. Both control groups showed
      homogenous staining in all B-cells. NSTZ rats perfused with 5.5 mM glucose had a
      marked diminution in GLUT2 staining. We observed no increase in GLUT2 staining in
      the NSTZ rats perfused with 0 mM glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397707
TI  - Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic
      resonance spectroscopy.
AB  - In spontaneously diabetic BB rats, the effect of chronically maintained blood
      glucose levels on the degree of energy failure and brain pH change during an
      ischemic insult, and on subsequent recovery after reperfusion, was studied with
      in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia
      (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic
      and nondiabetic male BB rats whose blood glucose levels were maintained with
      insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after
      ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic
      rats had an increased Pi peak intensity, with no significant pH change, compared
      with other groups. During ischemia, the rate and extent of hydrolysis of high
      energy phosphate metabolites (as measured by an increase in Pi) decreased, and
      the severity of tissue acidosis increased as preischemia blood glucose
      concentration increased. Among hyperglycemic BB rats, similar ischemia-induced
      changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and
      20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites
      associated with chronic hyperglycemia. Decline in PCr level during ischemia was
      not significantly different between groups. With reperfusion, both Pi and pH
      values rapidly returned to preischemia values. PCr levels, however, did not
      recover in hyperglycemic diabetic animals, with the degree of residual impairment
      dependent on the preischemia glucose level. Results suggest that optimal
      management of diabetes may lessen the degree of injury within the ischemic
      penumbra in diabetic patients who suffer a stroke.

PMID- 1397708
TI  - Further defects in counterregulatory responses induced by recurrent hypoglycemia
      in IDDM.
AB  - We evaluated the effect of previous experimental hypoglycemia on
      counterregulatory responses to hypoglycemia in 13 IDDM patients. These patients
      had defects in counterregulatory responses to hypoglycemia compared with 7
      nondiabetic control subjects. Plasma EPI and glucagon responses to hypoglycemia
      in IDDM patients were approximately 60% of levels in nondiabetic subjects (P less
      than 0.02 and P less than 0.001, respectively). Hepatic glucose output ([3
      3H]glucose) was reduced by approximately 60% of normal (P less than 0.005), and
      the glucose infusion rate required to maintain plasma glucose was correspondingly
      greater in people with IDDM (P less than 0.001). With a modified glucose clamp
      (plasma insulin approximately 330 pM), the diabetic subjects underwent two
      sequential 120-min periods of hypoglycemia (approximately 3.0 mM) with an
      intervening 60-min euglycemic recovery period. In the IDDM patients, there were
      30-50% decreases in plasma GH (P less than 0.005) and cortisol (P less than
      0.001) responses during the second hypoglycemic period compared with the first.
      In addition, glucose output, already defective compared with that in nondiabetic
      subjects, was further reduced by 33% (P = 0.03) during the second period of
      experimental hypoglycemia. There was no effect of repeated hypoglycemia on the
      responses of plasma glucagon, EPI, or NE, though plasma EPI was correlated
      directly with glucose output (P less than 0.001) and inversely with glucose
      uptake (P less than 0.05). There was no correlation between the rise in glucose
      output during hypoglycemia and antecedent glycemic control as measured by
      HbA1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397709
TI  - Inverse relationship between serum Lp(a) levels and first-phase insulin
      secretion.
AB  - Relationships between serum Lp(a) levels and insulin metabolism were investigated
      in 147 healthy nonobese men attending an executive health-screening program. Each
      subject received an IVGTT with measurement of plasma levels of glucose, insulin,
      and C-peptide. An inverse relationship was seen with the first-phase plasma
      insulin response when subjects were stratified into quartile ranges of the serum
      Lp(a) distribution. This relationship was supported by mathematical modeling
      analyses of these data, which revealed an inverse relationship between serum
      Lp(a) levels and first-phase pancreatic insulin secretion and plasma insulin
      responsiveness to glucose.

PMID- 1397710
TI  - Insulin secretory profiles and C-peptide clearance kinetics at 6 months and 2
      years after kidney-pancreas transplantation.
AB  - Glucose, insulin secretion, and insulin secretory pulses were measured by
      deconvolution of peripheral C-peptide concentrations in 10 IDDM recipients of a
      combined kidney-pancreas allograft 6 mo post-transplantation and were compared
      with 10 matched nondiabetic control subjects. Seven of the 10 recipients were
      restudied 2 yr post-transplantation. To control for immunosuppressive therapy, 6
      patients with a kidney allograft also were studied. Pancreatic insulin secretion
      rates were evaluated over a 24-h period with three mixed meals. Six months post
      transplantation, fasting (5.3 +/- 0.1 vs. 5.3 +/- 0.1 mM), average 24-h (6.0 +/-
      0.1 vs. 5.7 +/- 0.1 mM), and meal-related (6.1 +/- 0.3 vs. 5.8 +/- 0.2 mM) plasma
      glucose levels were not different in control subjects and recipients,
      respectively. Total 24-h insulin secretion rates were similar between the two
      groups (150 +/- 15 vs. 182 +/- 24 nmol.m-2.24 h-1). However, post
      transplantation, the relationship between basal and meal-stimulated insulin
      secretion was altered with increased basal insulin secretion (52.2 +/- 6.4 vs.
      97.4 +/- 12.5 pmol.m-2.min-1, P less than 0.004) and reduced meal-related
      secretion. The proportion of total 24-h insulin secretion comprised by basal
      secretion was 44 +/- 4% in the control subjects vs. 73 +/- 5% in recipients. The
      number of ultradian oscillations of insulin secretion identified in each 24-h
      period by pulse analysis was similar in control subjects and recipients (11.9 +/-
      0.9 vs. 10.4 +/- 0.5 oscillations/24 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397711
TI  - Recombinant glutamic acid decarboxylase (representing the single isoform
      expressed in human islets) detects IDDM-associated 64,000-M(r) autoantibodies.
AB  - GAD is an autoantigen in IDDM. Molecular cloning and specific antibodies allowed
      us to demonstrate that only the lower M(r) GAD64 isoform is expressed in human
      islets, in contrast to human brain, rat islets, and rat brain, all of which
      express both GAD64 and GAD67. Expression of the human islet GAD64 isoform in COS
      7 and BHK cells resulted in an enzymatically active rGAD64, which is
      immunoreactive with diabetic sera comparable with that of the islet 64,000-M(r)
      autoantigen. Immunoprecipitation analyses showed that 21/28 (75%) IDDM sera had
      rGA D64 antibodies compared with only 1/59 (1.7%) of the healthy control sera. In
      immunoblot analyses, an SMS serum--but only 1/10 randomly selected IDDM sera-
      recognized the blotted rGAD64 without relation to immunoprecipitation titers. In
      conclusion, only the GA D64 isoform is expressed in human islets, in contrast to
      rat islets, which also express the GAD67 isoform. The immunological properties of
      human rGAD64 are comparable with the native 64,000-M(r) islet autoantigen,
      allowing further studies of the immunopathogenesis of IDDM.

PMID- 1397712
TI  - Human small intestine facilitative fructose/glucose transporter (GLUT5) is also
      present in insulin-responsive tissues and brain. Investigation of biochemical
      characteristics and translocation.
AB  - A recent study by C.F. Burant et al. (13) demonstrates that GLUT5 is a high
      affinity fructose transporter with a much lower capacity to transport glucose. To
      characterize the potential role of GLUT5 in fructose and glucose transport in
      insulin-sensitive tissues, we investigated the distribution and insulin
      stimulated translocation of the GLUT5 protein in human tissues by immunoblotting
      with an antibody to the COOH-terminus of the human GLUT5 sequence. GLUT5 was
      detected in postnuclear membranes from the small intestine, kidney, heart, four
      different skeletal muscle groups, and the brain, and in plasma membranes from
      adipocytes. Cytochalasin-B photolabeled a 53,000-M(r) protein in small intestine
      membranes that was immunoprecipitated by the GLUT5 antibody; labeling was
      inhibited by D- but not L-glucose. N-glycanase treatment resulted in a band of
      45,000 M(r) in all tissues. Plasma membranes were prepared from isolated
      adipocytes from 5 nonobese and 4 obese subjects. Incubation of adipocytes from
      either group with 7 nM insulin did not recruit GLUT5 to the plasma membrane, in
      spite of a 54% insulin-stimulated increase in GLUT4 in nonobese subjects. Thus,
      GLUT5 appears to be a constitutive sugar transporter that is expressed in many
      tissues. Further studies are needed to define its overall contribution to
      fructose and glucose transport in insulin-responsive tissues and brain.

PMID- 1397714
TI  - Beta-cell antigen-specific lysis of macrophages by CD4 T-cell clones from newly
      diagnosed IDDM patient. A putative mechanism of T-cell-mediated autoimmune islet
      cell destruction.
AB  - Immunophenotyping of the early lesion in the pancreatic islets of Langerhans
      demonstrates a predominance of CD4+ lymphocytes, which may be preceded by an
      increase in islet macrophages. This observation implies that both types of cells
      may be involved in autoimmune-mediated beta-cell destruction leading to IDDM. In
      an attempt to attribute a role to beta-cell antigen-specific CD4-expressing T
      cell clones recently isolated from a newly diagnosed IDDM patient, we
      investigated whether such CD4 T-cells may be pathogenic in an in vitro
      cytotoxicity assay with HLA-DR-matched antigen-presenting macrophages as target.
      We report herein that, indeed, beta-cell antigen-specific CD4+ T-cells are
      capable of lysing macrophages in an antigen-specific fashion. This cytotoxicity
      is HLA-DR restricted, T-cell receptor complex mediated, and CD4 dependent. These
      observations imply that both helper T-cells and macrophages may be involved in
      the disease process via interaction between T-cells and macrophages pulsed with
      beta-cell antigen.

PMID- 1397713
TI  - Glucokinase and NIDDM. A candidate gene that paid off.
AB  - Glucokinase, the major enzyme that phosphorylates glucose upon entry into liver
      and islet beta-cells, has been considered a prime candidate for inherited defects
      predisposing to NIDDM. Now that the human gene has been isolated, this question
      has been addressed directly. Polymorphic markers flanking the gene were
      identified. These markers (microsatellites) are composed of variable numbers of
      dinucleotide repeats that vary in size, resulting in different alleles. Variably
      sized alleles can be typed rapidly from genomic DNA of individuals by the PCR.
      Studies of inheritance of glucokinase genes have revealed significant linkage in
      families with early-onset NIDDM, or MODY, and mutations have been identified
      within the coding region of the gene in some families. These studies are
      extremely encouraging, as they indicate that genes can be identified even in this
      heterogeneous genetic disorder. This study considers the phenotypes that result
      from glucokinase defects and the relationship of MODY to NIDDM, and it estimates
      the role of glucokinase defects in NIDDM in general.

PMID- 1397715
TI  - Features of insulin-resistance syndrome in men from French Caribbean Islands. The
      Telecom Study.
AB  - The prevalence of diabetes is known to be high in the West Indies, whereas CVD
      seems relatively rare. This apparently contradicts the existence of the insulin
      resistance syndrome, a cluster of metabolic abnormalities supposedly favoring
      both diabetes and cardiovascular complications. To address the question of
      whether this contradiction could be accounted for by specific features of this
      syndrome, we compared 1505 Caucasian and 181 Afro-Caribbean men, all participants
      in the French Telecom Study. The Afro-Caribbeans were of the same age and had the
      same BMI as the Caucasians; they also had significantly higher subscapular skin
      fold thickness and fasting insulin level, but similar BP and blood glucose level,
      and significantly lower plasma triglyceride level. Thus, although some features
      of the insulin-resistance syndrome were present (central adiposity and high
      insulin levels), none of the associated metabolic abnormalities were present.
      However, within the Afro-Caribbean group, subjects with plasma insulin
      concentrations above the median (> 52 pM) had higher mean BP and glucose and
      triglyceride levels compared with subjects with insulin concentrations < or = 52
      pM (P < 0.001). After adjustment for age and BMI, these differences, though
      smaller, still were statistically significant. These findings confirm that higher
      insulin concentrations are associated with higher levels of potentially
      atherogenic and diabetogenic metabolic parameters. However, depending on ethnic
      origin, the mean levels of these parameters seem to be different, with the
      consequence that, even if they are elevated with increasing insulin levels, they
      may not reach values high enough to determine a substantial risk of disease.

PMID- 1397716
TI  - Metabolic effects of suppression of nonesterified fatty acid levels with acipimox
      in obese NIDDM subjects.
AB  - NEFAs characteristically are elevated in obese NIDDM patients in both the basal
      state and after insulin. This elevation might aggravate glycemic control both by
      decreasing peripheral glucose disposal (glucose-fatty acid cycle), and by
      increasing HGO. Thus, lowering plasma NEFA levels might improve carbohydrate
      metabolism. We therefore measured HGO and fuel use (by indirect calorimetry) both
      in the basal state and during the last 30 min of a hyperinsulinemic clamp
      (0.025U.kg-1.h-1) in 8 obese NIDDM patients (BMI 34.8 +/- 1.0 kg/m2) after
      complete overnight suppression of plasma NEFA levels with acipimox, a new
      nicotinic acid analogue. After acipimox, mean basal plasma NEFA and glycerol
      levels were lower than control values (0.11 +/- 0.02 vs. 0.65 +/- 0.04 mM, P <
      0.001; and 16 +/- 3 vs. 68 +/- 7 microM, P = 0.004, respectively) and were
      accompanied by a fall in lipid oxidation (acipimox vs. placebo: 16.1 +/- 1.2 vs.
      38.8 +/- 2.4 mg.m-2 x min-1; P < 0.001) and a rise in glucose oxidation (91.1 +/-
      6.2 vs. 54.1 +/- 9.0 mg.m-2 x min-1; P = 0.002). Basal HGO and fasting plasma
      glucose levels were lower (94.1 +/- 9.2 vs. 118.5 +/- 9.5 mg.m-2 x min-1, P =
      0.01; and 8.3 +/- 1.2 vs. 9.8 +/- 1.2 mM; P < 0.001), respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1397717
TI  - Glycation of albumin, not glomerular basement membrane, alters permeability in an
      in vitro model.
AB  - The effects of glycation of either albumin, a plasma protein, or GBM were
      examined in an in vitro model of GBM permeability. Albumin was incubated with
      glucose in vitro, and nonglycated and glycated albumin were separated by affinity
      chromatography. Rat GBM was glycated either in vivo after the induction of
      diabetes or in vitro after incubation with 25 mM glucose. 150 micrograms of GBM
      was consolidated in an ultrafiltration cell, and albumin permeability across the
      GBM filter was assessed at an applied pressure (50 mmHg) selected to approximate
      glomerular capillary pressure in vivo. The sieving coefficient of glycated
      albumin was greater than the sieving coefficient of nonglycated albumin (0.25 +/-
      0.03 vs. 0.10 +/- 0.02; P < 0.05). GBM glycated in vivo in diabetic rats
      exhibited native albumin and water permeability that was indistinguishable from
      that for GBM from control rats. Similarly, GBM glycated in vitro by incubation
      with 25 mM glucose exhibited water and albumin permeability identical to that for
      GBM incubated in buffer. Thus, the glycation of albumin, but not of GBM, leads to
      enhanced permeability in an in vitro GBM filtration system. Increased
      permeability of glycated albumin may contribute to albuminuria and/or renal
      injury in states of increased circulating glycated albumin such as diabetes and
      experimental galactosemia.

PMID- 1397718
TI  - Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long
      Evans Tokushima Fatty (OLETF) strain.
AB  - A spontaneously diabetic rat with polyuria, polydipsia, and mild obesity was
      discovered in 1984 in an outbred colony of Long-Evans rats, which had been
      purchased from Charles River Canada (St. Constant, Quebec, Canada) in 1982. A
      strain of rats developed from this rat by selective breeding has since been
      maintained at the Tokushima Research Institute (Otsuka Pharmaceutical, Tokushima,
      Japan) and named OLETF. The characteristic features of OLETF rats are 1) late
      onset of hyperglycemia (after 18 wk of age); 2) a chronic course of disease; 3)
      mild obesity; 4) inheritance by males; 5) hyperplastic foci of pancreatic islets;
      and 6) renal complication (nodular lesions). Histologically, the changes of
      pancreatic islets can be classified into three stages: 1) an early stage (6-20 wk
      of age) of cellular infiltration and degeneration; 2) a hyperplastic stage (20-40
      wk of age); and 3) a final stage (at > 40 wk of age). These clinical and
      pathological features of disease in OLETF rats resemble those of human NIDDM.

PMID- 1397720
TI  - Effects of acute and chronic counterregulatory hormone infusions on glucose
      tolerance and insulin sensitivity in diabetic dogs.
AB  - The effects of elevated EPI and CORT levels on KG, SI, and SG were studied in
      dogs with alloxan-induced diabetes. Conscious dogs received SAL, EPI 20 ng.kg
      1.min-1 for 30 min (short EPI) or 72 h (long EPI), or CORT 200 micrograms.kg
      1.min-1 for 60 min (short CORT) or 72 h (long CORT) before assessment of glucose
      metabolism by rapid sampling for glucose and insulin levels after 300 mg/kg i.v.
      glucose and exogenous insulin infusion designed to simulate the normal secretory
      pattern. With EPI infusion, KG fell acutely from 2.9 +/- 0.4 to 2.0 +/- 0.2%/min
      (SAL vs. short EPI, P < 0.05), but rose to 3.4 +/- 0.4%/min during long EPI.
      Minimal-model analysis of the glucose response with the insulin data as input
      showed that SI decreased acutely from 4.7 +/- 1.8 to 2.5 +/- 0.6 x 10(-5) min
      1/pM (SAL vs. short EPI, P < 0.05), but rose to 4.5 +/- 2.5 x 10(-5) min-1/pM
      during long EPI. The effects of EPI on SG paralleled the results for KG and SI,
      with acute decline from 3.9 +/- 0.4 to 2.1 +/- 0.4 x 10(-2) min-1 (SAL vs. short
      EPI, P < 0.05) and recovery to 3.3 +/- 0.3 x 10(-2) min-1 during long EPI. During
      CORT infusion, KG tended to fall (SAL 2.9 +/- 0.4 vs. short CORT 2.5 +/- 0.5 vs.
      long CORT 2.2 +/- 0.5%/min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397719
TI  - Human GLUT4/muscle-fat glucose-transporter gene. Characterization and genetic
      variation.
AB  - Four overlapping DNA fragments spanning 32 kb containing the human GLUT4
      facilitative glucose-transporter gene were isolated and characterized. The
      sequence of the GLUT4 gene (approximately 6.3 kb) and 2.0 kb of the promoter
      region was determined. The sequence of the promoter revealed potential binding
      sites for transcription factors known to regulate gene expression in muscle cells
      and adipocytes. However, transfection of constructs including 2 kb of the GLUT4
      promoter fused to the bacterial CAT gene into 3T3-L1 adipocytes displayed only
      weak promoter activity. Because insulin resistance plays a prominent role in the
      development of NIDDM, genetic variation in the sequence of GLUT4 also was
      evaluated. Oligonucleotide primer pairs were selected that allowed the protein
      coding region of the human GLUT4 gene to be amplified by PCR. The sequence of the
      protein-coding region of the GLUT4 gene and all intron-exon junctions was
      determined for a single diabetic Pima Indian and was identical to that of the
      cloned gene and cDNA. SSCP analysis was used to screen patients with diabetes
      mellitus and normal, healthy nondiabetic individuals for mutations at the GLUT4
      locus. In addition to the silent substitution in the codon for Asn130 (AAC or
      AAT) and a Val383 (GTC)-->Ile(ATC) replacement described previously, two new
      variants were identified. One was a T-->A substitution in intron 1 that was found
      in 1 of 36 NIDDM patients who were typed for this variant. The second was a
      Ile385(ATT)-->Thr(ACT) replacement that occurred in 1 normal individual and was
      not found in any of 676 other normal and diabetic subjects. A large and racially
      diverse group of normal and diabetic individuals also was screened for the Ile383
      polymorphism. It occurred in both diabetic and nondiabetic subjects. There is no
      indication from our data that these polymorphisms are associated with NIDDM.

PMID- 1397721
TI  - Hyperglycemia markedly enhances skeletal muscle glycogen synthase activity in
      diabetic, but not in normal conscious rats.
AB  - Both hyperinsulinemia and hyperglycemia stimulate skeletal muscle glucose uptake.
      However, the intracellular metabolic fate of the phosphorylated glucose may be
      different when the prevalent stimulus for glucose uptake is hyperinsulinemia or
      hyperglycemia. To define the impact of hyperglycemia on the intracellular glucose
      disposal, we studied control and diabetic conscious rats under four experimental
      conditions: 1) basal insulin and basal glucose; 2) basal insulin and high
      glucose; 3) high insulin and basal glucose; and 4) high insulin and high glucose.
      Under both basal insulin (130 pM) and high insulin (2500 pM), hyperglycemia (15
      mM) increased glucose uptake and muscle and liver glycogen synthesis similarly in
      control and diabetic rats. Hyperglycemia resulted in a more significant decline
      in the muscle G-6-P concentration in diabetic rats than in control rats,
      suggesting activation of intracellular glucose metabolism. The diabetic skeletal
      muscle glycogen synthase was severely resistant to insulin stimulation compared
      with control (FV0.1 = 0.31 +/- 0.04 vs. 0.49 +/- 0.03; Km = 0.19 +/- 0.05 vs.
      0.10 +/- 0.01 mM; P < 0.01), but it was markedly responsive to glucose
      stimulation under both basal (FV0.1 = 0.38 +/- 0.03 vs. 0.21 +/- 0.03; Km = 0.10
      +/- 0.01 vs. 0.35 +/- 0.08 mM) and high insulin (FV0.1 = 0.65 +/- 0.07 vs. 0.31
      +/- 0.04; Km = 0.11 +/- 0.02 vs. 0.19 +/- 0.05 mM). By contrast, in control rats,
      hyperglycemia did not exert any stimulatory effect on skeletal muscle glycogen
      synthase. Thus, some metabolic alteration associated with the diabetic state
      renders the skeletal muscle glycogen synthase selectively responsive to glucose
      stimulation. This may represent a compensatory mechanism for the severe
      impairment in insulin's activation of this enzyme in diabetes.

PMID- 1397722
TI  - Characterization of glucose-induced in situ protein kinase C activity in cultured
      vascular smooth muscle cells.
AB  - The VSMC is an important target for the injurious effects of hyperglycemia in
      vivo. PKC plays a key role in the regulation of VSMC contraction and growth. This
      study examines whether elevated extracellular glucose concentrations (10-30 mM
      [180-540 mg/dl]) activate PKC in cultured rat VSMCs in vitro. A new, rapid, and
      highly specific assay was used to determine in situ PKC activity in digitonin
      permeabilized VSMCs. PKC activity in VSMCs responded rapidly to variations in
      extracellular glucose concentrations. PKC was activated significantly within 10
      min of exposure to D-glucose (20 mM) versus glucose (5 mM). Moreover, with
      continued exposure to D-glucose (20 mM), PKC activation was sustained for up to
      48 h. Reducing D-glucose concentrations to 5 mM restored PKC activity to control
      values within 1 h. PKC activation was also glucose-concentration dependent. A
      threshold of only 15 mM (270 mg/dl) was required to significantly and maximally
      activate PKC in VSMC. PKC was not activated in the presence of osmotic control
      media that contained either elevated mannitol or L-glucose concentrations. In
      marked contrast to the sustained PKC activation induced by D-glucose in VSMCs,
      the normal physiological PKC response to the pressor hormones, AII and AVP, was
      short-lived and returned to base line within minutes. Sustained PKC activation in
      the presence of elevated D-glucose concentrations in vitro could disturb the
      normal physiological regulation of VSMC function and growth and thereby may
      contribute to the apparent vasotoxicity of hyperglycemia in vivo.

PMID- 1397723
TI  - 1,25-Dihydroxyvitamin D3 prevents insulitis in NOD mice.
AB  - The active form of vitamin D, 1,25(OH)2D3, can prevent various forms of
      experimentally induced autoimmune disorders. The aim of this study was to confirm
      these findings in NOD mice that spontaneously develop an autoimmune type of
      diabetes mellitus. Therefore, the effect of a long-term 1,25(OH)2D3 treatment on
      the incidence of insulitis, the histological lesion preceding diabetes, was
      studied. Forty-three NOD mice were treated with 1,25(OH)2D3 (5 micrograms/kg)
      i.p. every other day from age 21 days on, when no insulitis was present yet. At
      day 100, 16 control mice receiving the treatment vehicle (arachis oil) had an
      incidence of insulitis of 75%, whereas only 41% of the 1,25(OH)2D3-treated
      animals developed insulitis (P < 0.025). Calcemia, determined 24 h after the last
      1,25(OH)2D3 injection was 2.5 +/- 0.1 mM, which was higher than in control
      animals (2.3 +/- 0.1 mM), but was well tolerated. Cellular immunity, as assessed
      with the mixed lymphocyte reaction performed at day 100, was not impaired
      significantly. This study demonstrates that long-term treatment with high doses
      of 1,25(OH)2D3 is able to decrease the incidence of insulitis in spontaneous
      autoimmune diabetes without major side effects.

PMID- 1397724
TI  - Linkage analysis of glucokinase gene with NIDDM in Caucasian pedigrees.
AB  - NIDDM has a strong genetic component, as evidenced by the high level of
      concordance between identical twins. The nature of the genetic predisposition has
      remained largely unknown. Recently, the glucokinase gene locus on chromosome 7p
      has been shown to be linked to a subtype of NIDDM known as MODY in French and
      British pedigrees, and glucokinase mutations have been identified. To study the
      relationship between the glucokinase gene and NIDDM, we performed a linkage
      analysis in 12 Caucasian pedigrees ascertained through a proband with classical
      NIDDM. The LINKAGE program was used under four models, including autosomal
      dominant and recessive, with individuals with glucose intolerance counted as
      either affected or of unknown status. Linkage was significantly rejected with the
      dominant models (LOD scores -4.65, -4.25), and was unlikely with the recessive
      model when glucose intolerance was considered as affected (LOD score -1.38).
      These findings suggest that mutations in or near the glucokinase gene are
      unlikely to be the major cause of the inherited predisposition to NIDDM in
      Caucasian pedigrees, but do not exclude a role for this locus with a polygenic
      model, or a major role in some pedigrees.

PMID- 1397725
TI  - Drooling.

PMID- 1397726
TI  - Drooling in the developmentally disabled: management practices and
      recommendations. Consortium on Drooling.

PMID- 1397727
TI  - Cerebral arterial and venous flow-velocity measurements in post-haemorrhagic
      ventricular dilatation and hydrocephalus.
AB  - Simultaneous anterior cerebral artery (ACA) and internal cerebral vein (ICV) flow
      velocities were measured in 18 babies with post-haemorrhagic ventricular
      dilatation (PHVD) and hydrocephalus (PHH). Compared with a control group matched
      for post-conceptional age, the resistance index of the ACA was increased. This
      was shown to occur at an early stage of PHVD in a longitudinal study of seven of
      the babies. There were no significant changes in ACA or ICV time-averaged
      velocities. Eight babies with PHH had ventricular taps on 18 occasions to relieve
      raised intracranial pressure. There was a significant decrease in the resistance
      index of the ACA, accompanied by an increase in the ACA time-averaged velocity,
      but no change in the ICV time-averaged velocity.

PMID- 1397728
TI  - Assessment of post-traumatic amnesia in young children.
AB  - To assess the duration of post-traumatic amnesia (PTA) in children, a new
      procedure is described, derived from a method described previously for adults.
      The procedure was tested on 70 healthy children between 3.5 and 10 years of age,
      then applied in a longitudinal prospective study of 54 children with brain damage
      resulting from closed head-injury. The procedure consistently measured PTA in
      children of various ages. The duration of PTA was found to be as good a
      prognostic indicator for the occurrence of long-term residual sequelae as is
      duration of coma.

PMID- 1397729
TI  - Rolandic spikes in the inter-ictal EEG of children: contribution to diagnosis,
      classification and prognosis of epilepsy.
AB  - The clinical correlates of Rolandic spikes were studied in 47 children to
      determine the significance of this EEG finding to the diagnosis and
      classification of epilepsy. The children were classified into 'functional' and
      'organic' groups, with and without epilepsy. Children with epilepsy were further
      subdivided into those with Rulandic and those with non-Rulandic seizures. In
      children without neurological abnormalities, the EEG finding of Rolandic spikes
      plays a decisive role in the diagnosis of an epileptic syndrome as benign focal
      epilepsy of childhood with centro-temporal spikes (BECT), a diagnosis with an
      excellent prognosis. Neurological and neuroradiological examinations of the
      'functional' group revealed that the Rolandic spike may occur as a true
      'functional' spike. The frequency of a family history of epilepsy among
      neurologically normal children with Rolandic spikes suggests, in addition to the
      inheritance of BECT and the EEG trait, the existence of a hereditary
      susceptibility to epilepsy.

PMID- 1397730
TI  - Planning an outing from hospital for ventilator-dependent children.
AB  - Returning ventilator-dependent children to the home environment has become a well
      accepted occurrence. The success of a home program depends on careful pre
      discharge planning in order to ensure the child's medical safety, and adequate
      preparation to ensure the child's and family's adjustment to an active community
      life after discharge. To achieve this, involvement in community activities must
      begin while the child is still in hospital. As part of a complete rehabilitation
      program, nine ventilator-dependent children were taken on an inpatient outing to
      Disneyland. The planning and goals of the outing are described.

PMID- 1397731
TI  - Medical cure of a brainstem abscess and serial brainstem auditory evoked
      potentials.
AB  - The brainstem abscess of a nine-year-old girl with tetralogy of Fallot was cured
      after six weeks of parenteral antibiotic therapy, without surgical intervention.
      Serial studies of brainstem auditory evoked potentials were undertaken until the
      patient was clinically normal. To the authors' knowledge, this is only the second
      medically cured case reported in the literature, and it is the first case studied
      with serial brainstem auditory evoked potentials. If the clinical status allows,
      medical treatment of a brainstem abscess with appropriate antibiotics could be
      tried before surgical intervention such as stereotactic aspiration for reducing
      the mass.

PMID- 1397732
TI  - What is the ideal sleeping position for infants?

PMID- 1397734
TI  - George Eliot and specific learning disorders.

PMID- 1397733
TI  - Evolution of plantigrade gait: is there a neuronal correlate?

PMID- 1397735
TI  - Effect of phospholipase A2 and ethanol on the survival of acinar cells isolated
      from the rat pancreas.
AB  - The study was undertaken to investigate the effect of phospholipase A2 (PLA2) on
      the viability of isolated pancreatic acinar cells (PACs) and its possible synergy
      with ethanol. The survival of PACs may be reduced by PLA2 in a dose-dependent
      manner. In the presence of 0.25 microgram PLA2.(10(6) cells)-1, all cells died
      within less than 4 h of incubation at 37 degrees C. A quantity of 180 mM ethanol,
      which alone was not lethal for PACs, increased the rate of cell death induced by
      PLA2 at a certain concentration of this enzyme. The present results imply that
      (1) PLA2 is able to damage PACs in the absence of additional substrates, and (2)
      at an appropriate activity of PLA2, ethanol may amplify the toxic effects of this
      lytic enzyme and force autodigestion of the pancreas.

PMID- 1397736
TI  - Effect of duodenal mucosal blood flow on duodenal alkaline secretion in rats.
AB  - To investigate the role of duodenal mucosal blood flow (DMBF) in the regulation
      of duodenal alkaline secretion (DAS), both parameters were measured before and
      after the administration of various drugs in rats. The DMBF was determined using
      an electrolytically generated hydrogen gas clearance technique, and the DAS was
      measured by the perfusion method. The administration of dulcerozine, a potent
      duodenal ulcerogenic agent, at a dose of 250 mg/kg and serotonin at a dose of 20
      mg/kg, which produces duodenal ulcerations with an acid load, decreased both DMBF
      and DAS. On the other hand, the administration of secretin at a dose of 10 U/kg
      increased both parameters. There were parallel changes in DMBF and DAS. It is
      concluded, therefore, that DAS may be regulated by DMBF and that both parameters
      may be involved in the defense mechanism of duodenal mucosa.

PMID- 1397737
TI  - Induction of duodenal ulcers in sensory deafferented rats following histamine
      infusion.
AB  - We used capsaicin as a selective probe for sensory neuronal mechanisms and
      examined in rats whether defunctionalization of the sensory nerves caused
      duodenal ulcers in the presence of acid hypersecretion. Chemical deafferentation
      was performed by subcutaneous injection of capsaicin for 3 days (total dose: 100
      mg/kg) 2 weeks before the experiment. This treatment did not cause by itself any
      damage in the duodenum. However, intravenous infusion of histamine (4, 8 and 16
      mg/kg/h) in these animals caused hemorrhagic lesions in the proximal duodenum
      within 6 h in a dose-dependent manner with an incidence of 100%. Histamine alone
      in the control animals did not induce macroscopically visible lesions at lower
      doses and caused only slight damage at the highest dose (16 mg/kg/h), although
      acid secretion was stimulated to the maximal degree at 8 mg/kg/h. Ablation of
      capsaicin-sensitive sensory neurons did not have any effect on acid secretion
      induced by histamine (8 mg/kg/h), but significantly inhibited the increase in
      duodenal HCO3- secretion in response to mucosal acidification. We conclude that
      functional ablation of capsaicin-sensitive sensory nerves impairs duodenal HCO3-
      secretory response to acid and results in duodenal ulcers if acid hypersecretion
      is present. These sensory nerves may be important in the defense mechanism of the
      duodenum against luminal acid.

PMID- 1397738
TI  - Nervous control of distension-induced relaxation of the porcine lower oesophageal
      sphincter.
AB  - The mechanisms involved in the relaxation of the lower oesophageal sphincter
      induced by distension of the oesophagus and different parts of the stomach, were
      studied in an anaesthetized porcine model. A computer technique was developed
      allowing on-line digitizing of lower oesophageal sphincter (sleeve device) and
      intragastric pressures. Basal sphincter tone was slightly reduced by truncal
      vagotomy, an effect which seemed to be reversed by sectioning of the
      vagosympathetic trunks in the neck. Balloon distension of the body of the
      oesophagus, relaxed the sphincter irrespective of the denervation procedures
      carried out. Distension of the whole stomach with increasing amounts of air
      induced a dose-dependent relaxatory lower oesophageal sphincter response, which
      was also closely associated with the subsequent increases in intragastric
      pressure. Denervation procedures did not alter this dose-response relationship.
      The importance of intramural mechanisms was illustrated by the abolition of
      distension-induced effects in most animals studied after transection of the
      gastro-oesophageal junction distal to the sphincter. Balloon distension of the
      antrum elicited a smaller but significant sphincter relaxation, but the
      mechanisms behind this response seemed to be more complex than after insufflation
      of air.

PMID- 1397739
TI  - Clinical significance of hypergastrinaemia: relevance to gastrin monitoring
      during omeprazole therapy.
AB  - During the early experience with omeprazole, it was recommended that plasma
      gastrin levels be monitored to identify patients with 4-5-fold increases above
      baseline. Such patients were thought to be at an increased risk of developing
      gastric carcinoid tumours. Studies have established that plasma gastrin levels
      usually rise 2-4-fold during omeprazole therapy, there being considerable inter-
      and intra-individual variation. Approximately 3.3% of patients have plasma
      gastrin levels above 400 pg/ml when treated continuously for 1 year. In clinical
      practice, it is not cost-effective to screen all patients to detect such a small
      percentage, particularly given the paucity of realistic treatment options in such
      patients, and the growing evidence that hypergastrinaemia during omeprazole
      treatment is of little, if any, clinical significance.

PMID- 1397740
TI  - Helicobacter pylori, peptic ulcer disease and inhibition of gastric acid
      secretion.
AB  - Recent studies have been reviewed to establish the possible importance of the
      interaction between Helicobacter pylori infection and gastric acid secretion. H.
      pylori infection results in increased gastrin release, but this does not lead to
      gastric acid hypersecretion and gastrin normalizes after eradication of the
      infection. An optimal, well-tolerated treatment strategy against H. pylori
      infection has not yet been clearly defined. One potentially useful approach may
      be to improve the antibacterial efficacy of antibiotics by effectively regulating
      gastric acidity. H2-receptor antagonists have no effect against H. pylori
      infection, while omeprazole (an acid pump inhibitor) appears to have a
      bacteriostatic action. Combination therapy with omeprazole and amoxycillin has
      been found to eradicate H. pylori in 50-80% of patients with duodenal ulcer,
      leading to a significant reduction in ulcer recurrence.

PMID- 1397741
TI  - Is endoscopy helpful in patient monitoring?
AB  - The safety issues involved in patients on long-term treatment with omeprazole
      will determine whether endoscopic monitoring is necessary. In a review of 646
      patients who have undergone regular gastric biopsies during continuous treatment
      with omeprazole, 10-120 mg daily, for periods of up to 5.5 years, there were no
      overall patterns to the changes in gastric endocrine cells. Apparent gastric
      endocrine cell hyperplasia in 72% of patients correlated with the development of
      chronic atrophic corpus gastritis. The only macroscopic changes to be reported
      were endocrine tumours in 4 out of 184 patients on long-term omeprazole for
      Zollinger-Ellison syndrome, and at least 3 of these patients had multiple
      endocrine neoplasia (MEN) type 1 syndrome. In patients with other low acid
      states, such as pernicious anaemia or after gastric irradiation or gastric
      surgery, in which drug therapy is not a confounding factor, there is a very low
      risk of developing macroscopic lesions within the stomach, and endoscopic
      surveillance is not routine practice. In conclusion, upper gastrointestinal
      endoscopic monitoring to identify microscopic or macroscopic changes cannot be
      justified during at least the first 5 years of continuous treatment with
      omeprazole.

PMID- 1397742
TI  - The potential clinical role of intravenous omeprazole.
AB  - The efficacy of intravenous omeprazole has been investigated in a number of
      clinical applications. In critically ill patients with bleeding peptic ulcer,
      which developed despite prophylactic measures for stress ulcer, bleeding stopped
      in 16 out of 19 patients treated with omeprazole given as a 40-mg i.v. bolus
      twice daily for up to 5 days. By contrast, bleeding stopped in only 3 out of 20
      such patients given a continuous infusion of ranitidine, 400 mg daily for the
      same time period. Dose-finding studies in volunteers showed that an initial bolus
      of omeprazole, 80 mg, followed by continuous infusion for 48 hours (8 mg/hour for
      the first 24 hours and 4 mg/hour for the subsequent 24 hours) produced elevation
      of gastric pH to 6 or above. This high-dose regimen when combined with infusion
      of large amounts of fluid was accompanied by peripheral oedema in three females,
      but did not occur when the dose was reduced to 4 mg/hour. In patients with non
      bleeding ulcers who were unable to take oral medication, treatment with an
      intravenous bolus of omeprazole, 40 mg twice daily, healed 91% of gastric ulcers
      and 88% of duodenal ulcers in 2 weeks. In patients with temporary impairment of
      gastric emptying, resulting from pyloric oedema secondary to an ulcer in this
      region, an intravenous bolus of omeprazole, 40 mg three times daily, led to
      resolution of pyloric stenosis in seven out of nine patients with pre- and intra
      pyloric ulcers, and in three out of five patients with post-pyloric
      ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397743
TI  - Epidemiology and natural history of gastro-oesophageal reflux disease.
AB  - Epidemiological studies of gastro-oesophageal reflux disease (GORD) are
      confounded by the lack of a standardized definition and a diagnostic 'gold
      standard' for the disorder. In Western countries, 20-40% of the adult population
      experience heartburn, which is the cardinal symptom of GORD, but only some 2% of
      adults have objective evidence of reflux oesophagitis. The incidence of GORD
      increases with age, rising dramatically after 40 years of age. There is also wide
      geographical variation in prevalence. Complications, including oesophageal ulcer
      and stricture, and Barrett's oesophagus, are found in up to 20% of patients with
      verified reflux oesophagitis. The signs and symptoms of GORD often wax and wane
      in intensity, and spontaneous remissions have been reported. In most cases,
      however, GORD is a chronic condition that returns shortly after discontinuing
      therapy. Although GORD causes substantial morbidity, the annual mortality rate
      due to GORD is very low (approximately 1 death per 100,000 patients), and even
      severe GORD has no apparent effect on longevity, although the quality of life can
      be significantly impaired. There are data to suggest that the use of non
      steroidal anti-inflammatory drugs (NSAIDs) contributes to oesophagitis and
      stricture formation in patients with GORD. Although these data are not
      conclusive, it seems prudent, if possible, to avoid the use of NSAIDs in patients
      with GORD, particularly those with oesophageal stricture.

PMID- 1397744
TI  - Long-term aims of treatment of reflux disease, and the role of non-drug measures.
AB  - Recent opinion about the long-term aims of treatment of reflux disease has been
      influenced substantially by the development of highly effective drugs that have
      minimal side-effects. The success of these drugs has emphasized the importance of
      gains in lifestyle resulting from relief of heartburn and other reflux-induced
      symptoms. Such relief is seldom achieved by traditional non-drug measures, which
      can also significantly impair lifestyle. In many patients with reflux disease,
      the effective relief of symptoms is a major aim. Oesophagitis, particularly when
      severe, carries a risk of developing peptic stricture or Barrett's oesophagus,
      but the risk factors associated with the development of these significant
      complications are not well identified. There is also no direct evidence that
      successful healing of oesophagitis by drug therapy is associated with prevention
      of local complications of oesophagitis, although many anecdotes regarding the
      resolution of peptic stricture by successful anti-reflux surgery support this
      possibility. Similarly, the linkage between development of Barrett's oesophagus
      and severe oesophagitis suggests that in some patients maintained healing of
      oesophagitis will prevent development or progression of Barrett's oesophagus.
      These considerations support the aim of healing of severe oesophagitis (i.e. more
      than patchy erosions), quite independently of the need to achieve effective
      symptom relief.

PMID- 1397745
TI  - Controlled clinical trials of omeprazole in the long-term management of reflux
      disease.
AB  - Reflux oesophagitis is a chronic relapsing disorder. When treatment is stopped
      after successful short-term healing of oesophagitis, high relapse rates (80%
      within 6 months) indicate that prolonged treatment is necessary in order to
      maintain remission. The results of three long-term, multicentre, controlled,
      double-blind clinical trials comparing different regimens of omeprazole with
      ranitidine are reviewed. Omeprazole, 20 mg daily, was found to be a highly
      effective maintenance therapy in patients with ulcerative oesophagitis, keeping
      67-89% of patients in remission for 1 year, compared with 10-25% of patients
      treated with ranitidine, 150 mg twice daily. Weekend omeprazole therapy, 20 mg
      daily every Friday, Saturday and Sunday, was, as with daily ranitidine,
      relatively ineffective. All treatment regimens were well tolerated and gastric
      mucosal biopsies showed no qualitative changes in gastric enterochromaffin-like
      cells.

PMID- 1397746
TI  - Appropriate acid suppression for the management of gastro-oesophageal reflux
      disease.
AB  - Gastro-oesophageal reflux disease (GORD) results from an abnormally prolonged
      dwell time of acidic gastric contents in the oesophagus. Although GORD is
      primarily a motor disorder, the injurious effects of gastric acid are central to
      the pathogenic process of oesophagitis, and the severity of disease correlates
      with the degree and duration of oesophageal acid exposure. In the majority of
      patients with mild disease, oesophageal acid exposure occurs predominantly during
      post-prandial periods. Conventional doses of H2-receptor antagonists cannot
      overcome the integrated stimulus to acid secretion resulting from a meal, and are
      thus relatively ineffective in preventing daytime, post-prandial oesophageal acid
      exposure. In patients with more severe grades of oesophagitis, there are
      abnormally high levels of nocturnal acid exposure, with the intra-oesophageal pH
      being less than 4.0 for 36% of the time, compared with 5% of the time in patients
      with mild GORD. Control of nocturnal acid secretion thus becomes increasingly
      important. This may be made worse by relative gastric acid hypersecretion in some
      patients with severe GORD. The long duration of action and effective inhibition
      of meal-stimulated acid secretion probably explains the superiority of omeprazole
      in treating GORD. Preliminary meta-analysis shows that the healing rate of
      erosive oesophagitis at 8 weeks by antisecretory agents is directly related to
      the duration of suppression of gastric acid secretion achieved over a 24-hour
      period (r = 0.87; p less than 0.05).

PMID- 1397747
TI  - Natural history of gastritis and its relationship to peptic ulcer disease.
AB  - Chronic gastritis is a common inflammatory disease. In a number of patients, the
      inflamed gastric mucosa shows a gradual tendency to become atrophic (atrophic
      gastritis). Gastritis tends to be lifelong, and spontaneous healing is rare. With
      very few exceptions (e.g. in patients with autoimmune chronic corpus gastritis),
      gastritis is associated with the presence of the bacterium Helicobacter pylori.
      Inflammation and atrophy of the gastric mucosa result in impairment of gastric
      secretory functions (e.g. secretion of gastric acid, pepsin and gastrin). Such
      impairment is dependent on the topographic type of gastritis; i.e. whether the
      inflammation and atrophy occur in the antrum (chronic antral gastritis), corpus
      (chronic corpus gastritis) or in both the antrum and corpus simultaneously
      (chronic pangastritis). Gastritis of different topographic types associates with
      different gastric diseases. In patients with H. pylori-related antral or
      pangastritis, peptic ulcer disease, and in particular duodenal ulcer, is common
      (with an incidence exceeding 20% after 10 years' follow-up), as compared with
      peptic ulcer disease, which is very rare in patients with a normal stomach.
      Gastric ulcer may sometimes occur in patients with a rather atrophic stomach, but
      both gastric and duodenal ulcers are extremely rare in patients in whom the
      gastritis accompanies severe atrophic changes in the corpus mucosa. Routine
      biopsies from the antrum and corpus, and interpretation of the results in the
      light of the data on gastritis and its atrophic sequelae, allow the
      gastroenterologist to predict the risk and likelihood of peptic ulcer disease in
      patients with gastritis.

PMID- 1397748
TI  - Inter-relationship between serum gastrin levels, gastric mucosal histology and
      gastric endocrine cell growth.
AB  - The development of gastric enterochromaffin-like (ECL)-cell hyperplasia in humans
      may be associated with extreme hypergastrinaemia, as occurs in Zollinger-Ellison
      syndrome (ZES) and pernicious anaemia (type A gastritis). More recently,
      endocrine cell hyperplasia has been found in all forms of chronic atrophic
      gastritis and even in cases of focal atrophy. Serum gastrin levels, non-antral
      gastric endocrine (argyrophil) cell growth, and the severity and type of
      concomitant gastritis were monitored in 66 unoperated and 8 antrectomized
      patients with poorly responsive peptic ulcer or reflux oesophagitis during up to
      5 years' treatment with high-dose omeprazole, 40 mg daily. A small subgroup of
      patients (23%) had serum gastrin concentrations of more than four times the
      normal upper limit. These patients also had hyperplasia of the gastric argyrophil
      cells. More importantly, the same subgroup of patients had high-grade (atrophic)
      gastritis. Micronodular hyperplasia of argyrophil cells was significantly more
      frequent in biopsies showing atrophic gastritis (48%) than in biopsies showing
      only superficial gastritis (3.6%). It is concluded that, as previously
      demonstrated in untreated patients with gastric ulcer, the argyrophil cell
      hyperplasia observed during high-dose omeprazole therapy is related to the
      progression of chronic atrophic gastritis rather than to serum gastrin levels.

PMID- 1397749
TI  - Gastric endocrine cells and gastritis in patients receiving long-term omeprazole
      treatment.
AB  - Both argyrophil endocrine cells and gastritis were investigated in 2,120 biopsies
      of gastric corpus mucosa from 443 out of 448 patients receiving long-term (for
      periods ranging from several months to 4 years) omeprazole treatment. None of the
      patients showed neoplasia or dysplasia, either endocrine or non-endocrine. In 123
      out of 443 patients (27.8%), endocrine hyperplasia of diffuse (9.3%), linear
      (4.1%) or micronodular (14.4%) type was detected either before or at some time
      during treatment. Chronic atrophic gastritis was found in 45 (10.2%) patients,
      60% of whom also showed micronodular hyperplasia. In patients with chronic
      atrophic gastritis, micronodular hyperplasia occurred in 49% of 96 biopsies,
      compared with 6% of 1,083 biopsies from patients with non-atrophic chronic
      gastritis and 2% of 941 biopsies from patients with no evidence of gastritis. In
      202 patients treated with omeprazole for at least 330 days, the incidence of
      micronodular hyperplasia increased from 2.5% at the first biopsy to 10.4% at the
      final biopsy, while the incidence of chronic atrophic gastritis increased from
      1.0% to 13.0%. The present and parallel studies suggest that progression of
      gastritis is inherent in the natural history of acid-related diseases, while
      endocrine cell changes are mostly secondary to gastritis-related gland atrophy
      and have no tumorigenic potential.

PMID- 1397750
TI  - Safety experience from long-term treatment with omeprazole.
AB  - Omeprazole was administered for up to 6 years in 859 patients for 'prevention of
      relapse in patients with poorly responsive peptic ulcer or reflux oesophagitis'.
      The pattern of adverse events reported during long-term treatment was similar to
      the adverse-event profile in short-term treatment with omeprazole (n = 2,818),
      ranitidine (n = 1,572) and cimetidine (n = 891). Omeprazole had essentially the
      same adverse-event profile as the two H2-receptor antagonists. The adverse-event
      profile for omeprazole during long-term treatment did not differ from that seen
      during short-term treatment with either omeprazole or the H2-receptor
      antagonists. The rate of occurrence of any specific adverse event decreased with
      time, and no previously unidentified adverse event occurred with long-term
      omeprazole therapy. There were no serious adverse events that were considered to
      be causally related to omeprazole therapy. Thus, omeprazole has been shown to be
      well tolerated in both short- and long-term treatment.

PMID- 1397751
TI  - EPC. European Pancreatic Club. XXIVth meeting. Ulm, Germany, October 11-14, 1992.
      Abstracts.

PMID- 1397752
TI  - Maturation of hearing aid benefit: objective and subjective measurements.
AB  - The goals of this investigation were to determine whether hearing aid benefit
      improved significantly over the first 10 weeks of hearing aid use and whether
      time-related changes in benefit (if any) were affected by the type of benefit
      measurement (i.e., objective or subjective). A total of 17 hearing-impaired
      subjects participated, with different subjects completing different phases of the
      study. Benefit was measured soon after the hearing aid fitting and again after 10
      weeks of adjustment to hearing aid use. Objective benefit data were determined
      using the Connected Speech Test. No significant changes in objective benefit were
      noted in noisy or reverberant listening environments when visual cues were
      available. However, in a low-noise setting and in a noisy setting without visual
      cues, improvements in objective benefit were seen over time. Subjective benefit
      data were derived from responses to the Profile of Hearing Aid Benefit. These
      data indicated significant benefit improvement over time in all five types of
      daily life situations assessed, although the improvement was small in reverberant
      and noisy environments. Significant, but modest, correlations were found between
      objective and subjective data for low-noise and reverberant listening
      environments. Comparison of experienced and novice hearing aid wearers suggested
      that although experienced wearers obtain more benefit than novice wearers, they
      evidence similar time-related changes in benefit during the first 10 weeks of new
      hearing aid use.

PMID- 1397753
TI  - Comparison of two methods for estimating the sensation level of amplified speech.
AB  - Several methods have been proposed to estimate the sensation level (SL) at which
      children receive amplified speech from their hearing aids. The present study
      compared the SL estimates obtained with two such methods: (1) a sound field aided
      audiogram approach, and (2) an electroacoustic approach that incorporated the use
      of a probe tube microphone system (Seewald, Ross, & Stelmachowicz, 1987). Sound
      field aided thresholds were obtained for 13 hearing-impaired subjects at eight
      audiometric frequencies. For the electroacoustic approach, in situ thresholds
      were obtained using a button-type hearing aid receiver attached to a custom
      earmold. Real ear aided responses were measured using a 70 dB RMS speech-weighted
      composite noise signal (Frye, 1986). A comparison of the frequency-specific SL
      estimates derived from the two different methods revealed that the sound field
      aided audiogram approach yielded higher SL estimates for 74% of the individual
      comparisons. A detailed analysis of the findings obtained from two subjects
      suggested that when the results of the two methods did not agree, the differences
      were due to an interaction between signal level and the unique input/output
      characteristics of the subjects' hearing aids. A precautionary measure is
      suggested for those who wish to use sound field aided threshold data to estimate
      the SLs at which children receive amplified conversational speech.

PMID- 1397754
TI  - Spectral distribution of /s/ and the frequency response of hearing aids.
AB  - The purpose was to determine a target for the upper frequency limit of a hearing
      aid that will provide access to the important spectral cues for all the sounds of
      English. The sibilant /s/ was studied because of its high-frequency content.
      Repeated tokens of /s/ were recorded from five men and five women before and
      between the vowels /u/, /a/, and /i/. Using fast Fourier transform analysis, the
      prominent spectral peak with the lowest frequency was identified and its center
      frequency determined for each token. This frequency averaged around 4.9 kHz for
      the /u/ context, 5.6 kHz for the /a/ context, and 6.0 kHz for the /i/ context.
      There were dramatic differences among talkers, with subject means ranging from
      3.2 to 8.4 kHz. The women generated consistently higher frequency /s/ sounds than
      the men, but there were also large differences within gender groups. These data
      suggest that the upper frequency limit of a high-fidelity hearing aid should be
      in the region of 10 kHz. If this cannot be accomplished with direct
      amplification, an alternative might be the selective use of frequency
      transposition.

PMID- 1397755
TI  - Mismatch negativity event-related potential elicited by speech stimuli.
AB  - The mismatch negativity (MMN) is a passively elicited event-related potential
      that is extremely sensitive to acoustic stimulus properties. The MMN was
      characterized in normal adults and school-age children in response to speech
      stimuli differing minimally in the onset frequency of the second and third
      formant transitions. The speech-evoked MMN consists of a negative waveform at
      about 230 msec that occurs in response to the deviant stimulus when it is
      presented in an oddball paradigm. It is absent in response to that same stimulus
      when presented alone. The MMN was clearly present in all adults and children
      tested. Using the procedures developed in this study, this event-related
      potential was found to be robust enough in individual subjects to be considered a
      potential clinical measure for assessing central auditory function in school-age
      children and adults.

PMID- 1397756
TI  - Threshold estimation using the "chained stimuli" auditory brain stem response
      technique.
AB  - The chained stimuli ABR method, which allows acquisition of data for a seven
      point latency-intensity function for both ears in approximately 35 min, is
      described. Testing of 22 ears with a simulated conductive loss, and 20 ears with
      sensorineural impairment, indicates that the chained stimuli method provides
      equivalent threshold estimates to that obtained with the conventional ABR
      measurement technique.

PMID- 1397757
TI  - Effect of hearing loss of cochlear origin on the auditory brain stem response.
AB  - Auditory brain stem response (ABR) testing is widely used to detect lesions of
      the auditory neural pathways. The ABR waves depend not only on the integrity of
      the neural pathways, but also on the condition of the cochlea. To properly
      interpret the ABR response, it is necessary to understand the effects of cochlear
      hearing loss on the ABR wave latencies. We studied two populations of subjects
      with cochlear hearing loss: one with varying degrees of high-frequency hearing
      loss and the other with varying degrees of flat configuration hearing loss. The
      degree of cochlear hearing loss was quantified in several different ways and
      subjected to one linear and three nonlinear regression analyses to test for
      accuracy in predicting ABR wave latencies and interpeak intervals (waves I, III,
      V, I-V, I-III, and III-V) for three click intensities. Hearing loss levels from 2
      to 6 kHz, in particular 4 kHz, were superior to other audiometric test
      frequencies as predictors of ABR wave latencies for the group with the high
      frequency losses. No particular characterization was found to be superior for the
      flat hearing loss configurations. From these results, modeled predictions of wave
      latencies as a function of degree and configuration of hearing loss were made.
      The modeled predictions are then used to suggest guidelines for interpretations
      of ABR results where hearing impaired patients are involved.

PMID- 1397758
TI  - A comparison of acoustic reflex and auditory brain stem response screening of
      high-risk infants.
AB  - This investigation was undertaken to explore the feasibility of screening for
      hearing impairment in an intensive care nursery population with a combined
      acoustic stapedius reflex-ABR approach. Acoustic reflex threshold measurements
      (AR) were made on intensive care nursery patients in an existing ABR screening
      program. Pass-fail results were determined for the two methods, separately and in
      combination. AR screening identified all 10 ears that failed the ABR screen. The
      cost savings of screening with a combined AR-ABR approach was determined for
      various pass-fail criteria. The results suggest that the AR-ABR approach can
      produce a significant cost savings without compromising the sensitivity and
      specificity of the screening program.

PMID- 1397759
TI  - Auditory responsiveness of premature infants utilizing visual reinforcement
      audiometry (VRA).
AB  - The purpose of this investigation was to study the relationship between visual
      reinforcement audiometry (VRA) performance and age (i.e., corrected and mental)
      with 60 premature infants. VRA performance was classified as unacceptable,
      marginal, or acceptable based on conditionability and number of responses
      obtained before habituation to the task. The results indicated that mental age
      and corrected age were significantly related to VRA performance. It was found
      that a corrected age of 8 mo and/or a mental age of 6 mo is typically required
      for acceptable performance using VRA. A lack of responsiveness to the VRA
      procedure at these ages would most likely be due to hearing loss as opposed to a
      general developmental delay. The data from this study would not support a large
      scale behavioral hearing screening program for premature infants below 8 mo
      corrected age or 6 mo mental age.

PMID- 1397760
TI  - Auditory perception changes after reimplantation in a child cochlear implant
      user.
AB  - The ability to remove cochlear implants from children and subsequently reimplant
      a more complex device in the same ear was the concern of this single case study.
      A postlinguistically deafened child, J.L., received a single-channel cochlear
      implant 1 yr after contracting meningitis and suffering a profound bilateral
      sensorineural hearing loss. After 3 yr of successful implant use, J.L. suffered
      an internal coil failure. She was then explanted and reimplanted with a
      multichannel cochlear implant in the same ear. This case report details her
      speech perception skills with her single-channel cochlear implant, a vibrotactile
      aid, and a multichannel cochlear implant. Results from auditory perceptual
      measures suggest that the explantation/reimplantation process was technically
      feasible with no adverse effects on J.L.'s ability to utilize a more
      sophisticated device and to exceed her previous performance levels.

PMID- 1397761
TI  - Performance over time with a nucleus or Ineraid cochlear implant.
AB  - This investigation determined whether the audiological performance of cochlear
      implant users varied with experience. Thirteen Nucleus and 14 Ineraid subjects
      were evaluated at 1, 9, and 18 mo after cochlear implant connection. Ten Nucleus
      and five Ineraid subjects were tested at 30 mo. On average, the ability of the
      subjects to recognize words and phonemes in an audition-only condition improved
      during the first 9 mo, as did their ability to recognize spondees in noise. The
      phoneme scores continued to improve during the next 9 mo. Environmental sound
      recognition improved gradually; significant improvement from the 1 mo scores was
      not noted until 18 mo. About half of the subjects who demonstrated poor word
      recognition at 1 mo showed significantly improved percent word correct scores by
      18 mo. The Nucleus and Ineraid subjects did not differ in their patterns of
      change over time. An information transmission analysis performed on the subjects'
      consonant confusion matrices showed relatively little change for the nasality and
      place features during the first 18 mo, and relatively large change for the voice,
      duration, and frication features. Most improvement in the feature scores occurred
      during the first 9 mo.

PMID- 1397762
TI  - Correlations of neuroanatomical measures to auditory brain stem response
      latencies.
AB  - Magnetic resonance imaging (MRI) was used to obtain measures presumed to scale
      the dimensions of the lower auditory pathway in humans for the purpose of further
      defining the relationship between length of the auditory pathway and auditory
      brain stem response (ABR) latencies. Specifically, measurements of soft tissue
      structures, that is, the eighth nerve and brain stem, were made for comparison
      with skull dimensions and ABR latencies. It was hypothesized that the brain stem
      dimensions covary significantly with skull dimensions and that the ABR parameters
      covary with both skull and brain stem dimensions. In general, only weak
      correlations were obtained with coefficients failing to reach statistical
      significance for most comparisons. These findings suggest that variance in ABR
      latencies cannot be attributed completely to variance in brain stem dimensions
      and raise suspicion that skull dimensions do not directly reflect brain stem
      dimensions.

PMID- 1397763
TI  - Improving the frequency specificity of the auditory brain stem response.
AB  - Several investigators have suggested that the use of tonal stimuli shaped with
      nonlinear windowing functions can improve the frequency specificity of the
      auditory brain stem response (ABR). This study investigated the effects of
      different windowing functions on the ABR for 30 normal-hearing adults and 30
      adults with high-frequency hearing loss. These hearing-impaired patients often
      produce an abnormal click-evoked ABR because of the influence of the high
      frequency loss. Each subject was evaluated using a click stimulus and a 500 Hz
      tone burst gated with one linear and four nonlinear windowing functions. There
      were no significant differences in wave V latency between the groups for any of
      the five windowed tone burst conditions. These results suggest that any of the
      windowing functions used would be effective for 500 Hz tonal ABRs with this
      population of hearing-impaired adults.

PMID- 1397764
TI  - The frequency-following response and the onset response: evaluation of frequency
      specificity using a forward-masking paradigm.
AB  - The onset and frequency-following response (FFR) components of the auditory brain
      stem response were investigated using a tone on tone forward-masking paradigm, as
      an alternate strategy to simultaneous masking, in an effort to further clarify
      the issue of place specificity of these components when elicited by a low
      frequency stimulus (500 Hz tone burst). The results of this preliminary
      investigation suggest that both the onset and FFR components yield frequency
      specific information, that is, they reflect activity along a limited apicalward
      region of the cochlea, but both are biased somewhat basalward to the place of the
      probe frequency. Also, of the two, the FFR is the relatively more place-specific
      response.

PMID- 1397765
TI  - The effect of cochlear hearing loss on auditory brain stem response latency.
AB  - The effect of audiometric configuration on the auditory brain stem response was
      studied in a large patient sample, and wave I latencies, wave V latencies, and
      the I-V interwave intervals were compared to those from a previous report.
      Patients with notched hearing losses showed longer wave V latencies and I-V
      interwave intervals than those with other audiometric configurations, but the
      magnitude of the effect was relatively small, and the confidence limit for
      cochlear diagnosis was essentially the same as that based upon a cochlear hearing
      loss population without regard to audiometric configuration.

PMID- 1397767
TI  - The clinical assessment of "Obscure Auditory Dysfunction" (OAD) 2. Case control
      analysis of determining factors.
AB  - Obscure Auditory Dysfunction (OAD) is defined as a clinical referral for self
      reported auditory disability with no audiometric abnormality by stringent
      criteria. In stage 2 of a case control study of OAD, we have confirmed the
      general finding of stage 1 that OAD is multifactorial; compared with controls,
      patients as a group have a genuine performance deficit for understanding speech
      in noise, accompanied by personality-related factors. Paired logistic regression
      analysis optimally differentiated the 50 patients from their 50 matched controls
      on the basis of variables from three different domains: masked thresholds
      (psychoacoustic domain), dichotic listening ability (central/cognitive domain),
      and underestimation of own hearing ability (personality domain). A further and
      influential contributing variable was understanding of speech in noise
      supplementing the variables in both the psychoacoustic and the cognitive domains.
      With this model, 82.7% of the total group deviance was explained (i.e., the
      binary variable of case/control). A corresponding discriminant function analysis
      correctly classified 80% of patients and 90% of controls. When factors underlying
      the performance and personality-related variables were investigated with multiple
      linear regression within the two groups separately, relatively little of the
      within-group variance among OADs was explained. This is consistent with the
      multifactorial nature of OAD, in that the combinations of factors leading to OAD
      status differ between individuals. The research findings have been used to design
      a clinical test package to provide diagnostic information on the basis of OAD in
      individuals.

PMID- 1397766
TI  - Strategies for increasing response behavior of 1- and 2-year-old children during
      visual reinforcement audiometry (VRA).
AB  - This study investigated strategies for increasing the number of responses that
      can be obtained from young children during visual reinforcement audiometry.
      Subjects included normal 1- and 2-yr-old children. Responses before habituation
      were studied as a function of age, reinforcer conditions, and test sessions. It
      was found that: (1) using two reinforcers led to more responses before
      habituation than use of a single reinforcer; (2) after habituation in test
      session 1 and a 10-min break, most 1-yr-olds demonstrated a minimum of five
      additional responses in test session 2; and (3) 2-yr-olds habituated more rapidly
      than 1-yr-olds.

PMID- 1397768
TI  - Performance with an adaptive frequency response hearing aid in a sample of
      elderly hearing-impaired listeners.
AB  - This study assessed the efficacy of an adaptive frequency response hearing aid
      (AFR) for improving speech perception ability in noise among a group of elderly
      hearing-impaired listeners. A speech recognition task, self-assessed speech
      intelligibility task, and qualitative judgment task were administered to examine
      subtle differences in the effects of the AFR "signal processing" versus linear
      amplification. Group scores showed statistically significant improvement with AFR
      processing on the speech recognition task involving high-predictability
      sentences, but not on any other measures. However, there was a trend toward
      improved scores with AFR processing for low-predictability sentences as well.
      These results suggest that AFR circuitry may be most useful for enhancing
      recognition of speech in high-cue contexts. Wide individual subject variability
      was observed on all measures. This demonstrates the importance of evaluating the
      effectiveness of noise reduction hearing aids on an individual basis and with
      more than one task.

PMID- 1397770
TI  - Age-related asymmetry on a cued-listening task.
AB  - We report results on a cued-listening task designed to simulate the listening
      problems commonly described by individuals with sensorineural hearing loss,
      especially those experienced by elderly persons. Against a background of
      multitalker babble, the subject detected targets embedded in continuous
      discourse. Noncoherent segments of this discourse were presented simultaneously
      from loudspeakers on the right and left sides. A signal light cued the side to be
      monitored during a listening trial. The overall difficulty of the task was
      manipulated by variation of the message to competition intensity ratio. A
      sequence of listening trials, half-cued to the right side, half cued to the left
      side, was executed at each of four message to competition intensity ratios.
      Nineteen young adults with normal hearing and 28 elderly persons with
      presbyacusic hearing loss were evaluated. All subjects, young and elderly, were
      able to complete the cued-listening task successfully. Results showed a small but
      significant right-side advantage in the young group and a substantial right-side
      advantage in the elderly group. The application of the testing technique to the
      evaluation of hearing aid performance is illustrated in two elderly persons.

PMID- 1397769
TI  - Effects of noise and noise suppression on speech perception by cochlear implant
      users.
AB  - The recognition of phonemes in consonant-vowel-consonant words, presented in
      speech-shaped random noise, was measured as a function of signal to noise ratio
      (S/N) in 10 normally hearing adults and 10 successful adult users of the Nucleus
      cochlear implant. Optimal scores (measured at a S/N of +25 dB) were 98% for the
      average normal subject and 42% for the average implantee. Phoneme recognition
      threshold was defined as the S/N at which the phoneme recognition score fell to
      50% of its optimal value. This threshold was -2 dB for the average normal subject
      and +9 dB for the average implantee. Application of a digital noise suppression
      algorithm (INTEL) to the mixed speech plus noise signal had no effect on the
      optimal phoneme recognition score of either group or on the phoneme recognition
      threshold of the normal group. It did, however, improve the phoneme recognition
      threshold of the implant group by an average of 4 to 5 dB. These findings
      illustrate the noise susceptibility of Nucleus cochlear implant users and suggest
      that single-channel digital noise reduction techniques may offer some relief from
      this problem.

PMID- 1397771
TI  - Central auditory processing disorders in the elderly: the effects of pure tone
      average and maximum word recognition.
AB  - We previously examined central auditory processing disorders and the effect of
      age in 1026 64- to 93-yr-olds. Here, we correlated three indices of central
      auditory processing disorders with age, pure tone averages (PTA) and maximum word
      recognition scores. With one exception, correlations of indices with PTA equaled
      or exceeded those with age. With one exception, correlations with word
      recognition scores were insignificant or smaller than those with age. Although
      statistically significant, the magnitudes of most effects were small (0.003 less
      than r2 less than 0.146). However, PTA accounted for approximately 30% of the
      variability in corrected Staggered Spondaic Word test error scores.

PMID- 1397772
TI  - Comparison of continuous and pulsed stimuli in contralateral acoustic reflex
      threshold measurements.
AB  - Continuous pure-tone stimuli are traditionally used for contralateral acoustic
      reflex threshold (ART) testing. The GSI-33 middle ear analyzer provides an option
      of pulsed stimuli for contralateral ART testing. This study compared ARTs for the
      steady and the pulsed stimuli for 100 ears. Lower ARTs were consistently obtained
      with the continuous rather than the pulsed stimulus for more than 90% of the
      thresholds.

PMID- 1397773
TI  - Addendum to "transfer functions and correction factors used in hearing aid
      evaluation and research".
AB  - In an earlier publication, various transformations used in hearing aid research
      and its application were summarized. As a result of continued interest and
      requests, additional transfer functions are provided in this addendum.

PMID- 1397774
TI  - Glomerular structural changes in type 1 (insulin-dependent) diabetes mellitus:
      causes, consequences, and prevention.
AB  - Diabetic nephropathy is caused primarily by advanced glomerulopathy, the renal
      expression of diabetic microangiopathy. With stereological methods a quantitative
      description of the structural changes is achieved. The glomerulopathy is
      characterized by an increase in basement membrane material: thickening of the
      capillary wall and an increase in mesangial volume relative to glomerular volume,
      comprising increase in matrix. Among groups of patients conformity between renal
      function stage and structure exists. The parameters measuring glomerulopathy are
      normal at the onset of diabetes; patients with normoalbuminuria may show slight
      basement membrane thickening, or normal parameters; the microalbuminuric group
      shows a measurable, but moderate glomerulopathy; patients with overt nephropathy
      have advanced lesions; at this stage heterogeneity among glomeruli makes the
      estimates weaker. Recent data indicate that the changes in peripheral basement
      membrane and in mesangial matrix develop in concert and both contribute to the
      early stage of glomerulopathy in patients with microalbuminuria. As to the
      consequences of the structural changes the mechanism of albuminuria is not clear.
      It is suggested that the early glomerulopathy entails other structural
      modifications, including formation of new vessels which may be the site of
      leakage. The marked deviations in glomerular filtration rate correspond well with
      estimates of filtration surface area: in the early hyperfunction state it is
      increased; in advanced nephropathy it is decreased, due to advanced
      glomerulopathy in conjunction with glomerular occlusion. The diabetic state is
      the necessary condition for the glomerulopathy. In relating structural changes to
      presumed contributing causes no supporting evidence of a relationship with
      glomerular hyperfunction or hypertrophy was observed. The structural parameters
      may be useful tools in clinical trials aiming at arresting the development of
      glomerulopathy, and thereby providing a prevention of diabetic nephropathy.

PMID- 1397775
TI  - Potential use of glutathione for the prevention and treatment of diabetic
      neuropathy in the streptozotocin-induced diabetic rat.
AB  - It has been shown that parameters of oxidative stress are increased in
      experimental diabetic neuropathy. The glutathione redox system is one of the
      intracellular scavenger systems for neutralizing free oxygen radicals. In this
      investigation we studied the effect of glutathione-treatment on the development
      of diabetic neuropathy in streptozotocin-induced diabetic rats by measuring
      sensory and motor nerve conduction velocities. The total study period was 10
      weeks. Four groups of rats were studied: Group 1 consisted of non-diabetic, age
      matched control rats; Group 2, of diabetic rats treated with placebo from week 0
      to 10; Group 3, of diabetic rats treated with 200 mg glutathione/kg body weight
      i.v. two times per week from weeks 0 to 10; and Group 4, of diabetic rats treated
      with placebo from weeks 0 to 4 and as Group 3 from weeks 4 to 10. The sensory and
      motor nerve conduction velocity of rats treated prophylactically with glutathione
      (Group 3) were significantly different from those of rats treated with placebo
      (Group 2) or with glutathione administered at a later time point (Group 4).
      Complete restoration of sensory and motor nerve conduction velocity was not
      reached. There was a significant improvement in motor nerve conduction velocity
      from weeks 4 to 6 (p less than 0.005), but not in sensory nerve conduction
      velocity in the delayed treatment group (Group 4). In conclusion, treatment with
      glutathione, a free radical scavenger, is partially effective in the prevention
      of diabetic neuropathy in streptozotocin-induced diabetic rats, but is of limited
      value when the neuropathy is already present.

PMID- 1397776
TI  - Differential growth of brain and retinal bovine pericytes.
AB  - Within the central nervous system, pericyte degeneration in diabetes mellitus
      occurs only in the retinal microcirculation and is not seen in the brain. This
      study sought to elucidate differences between bovine retinal and brain pericytes.
      When pairs of retinal and brain pericytes from individual calves were cultured in
      vitro, the morphological organisation of early post-confluent retinal pericyte
      cultures was consistently different from that of brain pericyte cultures. When
      retinal and brain pericyte cultures were grown to second passage in high or
      normal glucose medium supplemented with fetal calf serum, brain pericyte cultures
      grew significantly faster than retinal pericytes in either medium (p less than
      0.0001). Brain pericytes thus appeared to grow intrinsically faster than retinal
      pericytes and this effect was largely independent of glucose concentration. Brain
      pericytes also grew faster than retinal pericytes in high glucose medium
      containing human diabetic or control serum (p less than 0.002). The proliferative
      effect of serum from diabetic patients with non-proliferative diabetic
      retinopathy on pericytes grown in high glucose medium was not significantly
      different from that of control serum. Both brain and retinal pericytes showed
      variation in their ability to replicate in high concentrations of glucose. The
      selectivity of pericyte degeneration to the retinal circulation does not appear
      to be due to changes in the mitogenic activity of diabetic serum for retinal
      pericytes, but may relate to the intrinsic relative inability of the retinal
      pericyte to reproliferate in response to the metabolic injury of diabetes
      mellitus.

PMID- 1397777
TI  - Effects of previous glycaemic control on the onset and magnitude of cognitive
      dysfunction during hypoglycaemia in type 1 (insulin-dependent) diabetic patients.
AB  - To determine whether the degree of previous glycaemic control may modify
      cognitive responses to hypoglycaemia, the glycaemic thresholds for, and magnitude
      of cognitive dysfunction as assessed by P300 event-related potentials as well as
      subjective and hormonal responses during hypoglycaemia were evaluated.
      Hypoglycaemia was induced by intravenous insulin infusion in 18 Type 1 (insulin
      dependent) diabetic patients, 7 of whom were strictly controlled (HbA1c: 6.3 +/-
      0.3%; mean +/- SEM; Group 1) and 11 of whom were poorly controlled (HbA1c: 9.1 +/
      0.4%; Group 2). Within 60 min, mean blood glucose declined from 5.6 and 5.7
      mmol/l (baseline) to a nadir of 1.6 and 1.8 mmol/l followed by an increase to 5.6
      and 4.3 mmol/l after 120 min in Group 1 and 2, respectively. There was no
      significant difference between the groups in regard to P300 latency at baseline,
      but between 50 and 70 min a significant prolongation of this component was noted
      in Group 2 as compared with Group 1 at blood glucose levels between 1.6 and 2.3
      mmol/l (p less than 0.05). The glycaemic thresholds at which a significant
      increase of P300 latency over baseline was first noted were 1.6 +/- 0.2 mmol/l in
      Group 1 and 3.5 +/- 0.2 mmol/l in Group 2 (p less than 0.05). The glucose
      thresholds at which this prolongation was no longer demonstrable were 1.9 +/- 0.1
      mmol/l in Group 1 and 3.8 +/- 1.4 mmol/l in Group 2, respectively (p less than
      0.05). The glycaemic threshold at which the P300 amplitude was first
      significantly reduced was 2.2 mmol/l in Group 2, whereas no such reduction was
      observed in Group 1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397779
TI  - The number of glomeruli in type 1 (insulin-dependent) and type 2 (non-insulin
      dependent) diabetic patients.
AB  - The number of glomeruli per kidney in Type 1 (insulin-dependent) and Type 2 (non
      insulin-dependent) diabetic patients was estimated by an unbiased stereological
      method: the fractionator. No significant differences were observed between Type 1
      and Type 2 diabetic patients without severe diabetic glomerulopathy and non
      diabetic patients. Diabetic patients with proteinuria who were in the early
      stages of diabetic nephropathy also had a normal number of glomeruli. On the
      other hand, a subgroup classified as Type 1 diabetic patients with severe
      diabetic glomerulopathy had significantly less glomeruli compared with Type 1
      diabetic patients with mild or no glomerulopathy. A probable explanation is that
      Type 1 diabetic patients lose glomeruli in relation to the progression of
      diabetic glomerulopathy. A more theoretical alternative is, however, that
      development of diabetic glomerulopathy is facilitated by a low number of
      glomeruli.

PMID- 1397778
TI  - The effects of sympathetic nervous system activation and psychological stress on
      glucose metabolism and blood pressure in subjects with type 2 (non-insulin
      dependent) diabetes mellitus.
AB  - The sympathetic nervous system may contribute to excessive hepatic glucose output
      in Type 2 (non-insulin dependent) diabetes mellitus and could be implicated in
      the interrelated problem of hypertension. The aim of these studies was to
      determine whether subjects with Type 2 diabetes had normal sensitivity (compared
      with age- and weight-matched non-diabetic subjects) to noradrenaline infusion (60
      ng.kg-1.min-1 for 60 min) and to compare the responses with oral tyramine
      administration (800 mg), and psychological stress (using competitive computer
      games). Noradrenaline infusion caused significantly greater plasma glucose (mean
      increment 2.1 +/- 0.4 vs 0.6 +/- 0.1 mmol/l, p less than 0.005) and pressor
      responses (mean systolic increment 21 +/- 3 vs 11 +/- 1 mmHg, p less than 0.02)
      in the diabetic subjects. The excessive glycaemia was due to increased hepatic
      glucose output rather than reduced glucose disposal. Tyramine administration
      caused significantly increased hepatic glucose output and plasma glucose levels,
      but with similar responses in the diabetic and non-diabetic subjects; the pulse
      and pressor responses were also similar between the groups. The psychological
      stressor induced significant increases in pulse, blood pressure and non
      esterified fatty acid levels in the combined group of subjects (p less than 0.01)
      but did not influence plasma glucose levels in either diabetic or non-diabetic
      subjects. We conclude that pharmacologically-induced sympathetic nervous
      stimulation can induce hyperglycaemia. Subjects with uncomplicated Type 2
      diabetes have increased sensitivity to exogenous noradrenaline but may not
      hyperrespond to endogenous sympathetic activation.

PMID- 1397780
TI  - A population-based prevalence survey of known diabetes mellitus in northern Italy
      based upon multiple independent sources of ascertainment.
AB  - The aims of this survey were (1) to estimate the prevalence of known diabetes
      mellitus in 1988 in Casale Monferrato (Northern Italy); (2) to validate different
      data sources available in Italy; (3) to identify a population-based cohort of
      diabetic patients. Multiple independent data sources were used and the capture
      recapture method was applied to estimate the completeness of ascertainment of the
      survey. The primary data source was the list of all patients attending the
      diabetic clinic or those referred by family physicians and paediatricians of the
      area. The secondary data sources were the list of hospital discharges, the
      prescriptions data source and the list of all people using reagent strips and
      insulin syringes. On 1 October 1988 (the cut-off date) 2,069 cases of known
      diabetes were identified. The estimated completeness of ascertainment of the
      survey was 91%. Prevalence of known diabetes, Type 1 (insulin-dependent), Type 2
      (non-insulin-dependent) and insulin-treated diabetes were, respectively, 2.21%
      (95% CI 2.13-2.29), 0.80/1,000 (0.62-0.98) and 2.10% (2.01-2.19), 2.92/1,000
      (2.57-3.27). A higher prevalence of Type 2 diabetes was observed in women (2.30%,
      2.18-2.42) than in men (1.88%, 1.76-2.00). Age-specific prevalence of Type 2
      diabetes increased with age. Computerized data sources routinely available in the
      Piedmont Region (hospital discharges and prescriptions data sources) showed a low
      completeness of ascertainment when considered together (65%, 1,338 of 2,069),
      indicating the need to involve the diabetic clinic and family physicians in the
      ascertainment of known diabetes. In conclusion, the prevalence of known diabetes
      in Italy was lower than in Northern Europe and the United States.

PMID- 1397781
TI  - Renal excretion of kallikrein and eicosanoids in patients with type 1 (insulin
      dependent) diabetes mellitus. Relationship to glomerular and tubular function.
AB  - Glomerular filtration rate, renal plasma flow, renal tubular sodium reabsorption
      (derived from lithium clearance) and renal excretion rates of kallikrein,
      prostaglandin E2 and systemic and renally-derived metabolites of prostacyclin and
      thromboxane A2 were measured in patients with Type 1 (insulin-dependent) diabetes
      mellitus and in normal subjects. Diabetic patients with glomerular
      hyperfiltration had greater active kallikrein and prostaglandin E2 excretion than
      patients with normal glomerular filtration rate or than normal control subjects.
      Both active kallikrein and prostaglandin E2 excretion correlated directly with
      glomerular filtration rate. Active kallikrein excretion correlated directly with
      the reabsorption of sodium in the distal tubule. The excretion rates of 6-keto
      prostaglandin F1 alpha, 2,3 dinor 6-keto prostaglandin F1 alpha, thromboxane B2,
      2,3 dinor thromboxane B2 and 11-dehydro thromboxane B2 excretion were not
      different between the groups. This study confirms in man our previous finding of
      increased renal kallikrein production in the hyperfiltering streptozotocin
      diabetic rat model. Given that kinins generated by kallikrein are extremely
      potent vasodilators and stimulate the renal production of eicosanoids that also
      regulate glomerular function, our findings suggest that increased kallikrein
      activity and prostaglandin E2 production may contribute to renal vasodilatation
      and hyperfiltration in human diabetes. The localization of kallikrein in the
      distal connecting tubule makes it plausible that altered sodium transport in the
      distal tubule may be a signal to increase generation of kallikrein.

PMID- 1397782
TI  - Generation of thrombin activity in relation to factor VIII:C concentrations and
      vascular complications in type 1 (insulin-dependent) diabetes mellitus.
AB  - A possible association between plasma coagulant activity and the presence of
      vascular complications in patients with diabetes mellitus was studied by
      measuring the generation of thrombin in plasma of 20 control subjects and 50
      diabetic patients classified according to the presence or absence of
      microvascular complications. Thrombin production was determined in defibrinated
      plasma using a semi-automated technique with measurement of thrombin activity
      using chromogenic peptide S2238. Values determined were the lag time to
      appearance of thrombin activity and time taken to generate 50% maximal thrombin
      activity. Thrombin activity was related to concentrations of coagulant factor
      VIII activity and fibrinopeptide A and these were correlated with HbA1C levels.
      The median time to generate 50% maximal thrombin activity was not significantly
      reduced in diabetic patients compared with control subjects (53 vs 54 s, p =
      0.076) and there were no significant differences between patients with and
      without microvascular complications. There were no differences in median
      fibrinopeptide A concentrations between the diabetic and control subjects (1.5 vs
      2.2 nmol/l, p = 0.169). Time to 50% maximal thrombin activity correlated
      inversely with factor VIII:C concentrations in diabetic patients (r = -0.344, p =
      0.015, n = 50) and both this and lag time correlated with factor VIII:C in
      diabetic patients and control subjects combined (r = -0.395, p less than 0.01; r
      = -0.327, p = 0.006, n = 70). Factor VIII:C concentrations increased with age of
      the subject and with HbA1C concentrations. The results failed to show enhancement
      of coagulation in contact-activated diabetic plasma compared with control plasma
      and suggest that a relationship between high levels of factor VIII:C in diabetes
      and the development of mcirovascular complications is unlikely to be mediated
      through procoagulant activity in plasma.

PMID- 1397784
TI  - Incidence and prevalence of type 1 (insulin-dependent) diabetes mellitus in
      Icelandic children 1970-1989.
AB  - Through use of primary and secondary data sources for registration and
      validation, the incidence and prevalence of Type 1 (insulin-dependent) diabetes
      mellitus in children aged 0-14 years in Iceland has been completely ascertained
      for the years 1970-1989. The age-adjusted mean annual incidence per 100,000 for
      the 20-year period was 9.4 (95% confidence interval 7.8-11.3); similar for boys
      (9.9; 7.7-12.7) and girls (8.8; 6.7-11.5). Between 1970-1979 the incidence was
      8.0 (6.0-10.6) and between 1980-1989 it was comparable at 10.8 (8.4-13.8) (p
      greater than 0.10). By Poisson regression analysis the variation in incidence was
      related to age at diagnosis (p less than 0.001), while a linear trend for
      calendar year at diagnosis did not reach statistical significance (p = 0.07). A
      quadratic curve, however, better described the temporal variation in incidence (p
      less than 0.05). The total prevalence per 1,000 by the end of 1979 and 1989 was
      similar, 0.45 (0.30-0.65) and 0.57 (0.40-0.79), respectively. In conclusion, this
      study confirms that both the incidence and prevalence of childhood Type 1
      diabetes in Iceland are low compared to the other Nordic countries. The findings
      may suggest a causative role for environmental factors that are not related to
      latitude or ambient temperature.

PMID- 1397785
TI  - Cyclosporin A treatment of young children with newly-diagnosed type 1 (insulin
      dependent) diabetes mellitus. London Diabetes Study Group.
AB  - Several studies have demonstrated the efficacy of cyclosporin A in modifying the
      initial course of Type 1 (insulin-dependent) diabetes mellitus in older children
      and adults but none have reported the effects in very young children. We treated
      14 newly-diagnosed Type 1 diabetic patients aged 22 months to 95 months with
      cyclosporin A. Mean insulin dose at entry was 0.7 +/- 0.07 IU.kg-1.day-1. Initial
      cyclosporin A dose was 10 mg.kg-1.day-1. Insulin dose reached a nadir of 0.13
      IU.kg-1.day-1 by 180 days. Mean glucagon-stimulated connecting peptide levels
      were maximal at 6 months (0.75 nmol/l) and were maintained while on cyclosporin
      A. Insulin was discontinued in four patients for 4, 12, 15 and 30 months
      respectively. In five other patients the insulin dose was less than 0.15 IU.kg
      1.day-1 for at least 3 months. Glycated haemoglobin levels for all patients were
      within the normal range. Side effects included anorexia, stomach pains, poor
      weight gain, hypertrichosis, gum hyperplasia, mild anaemia and elevated
      creatinine. All patients have now discontinued cyclosporin A and all but one have
      been followed for 5 years after discontinuation. Reasons for discontinuing
      cyclosporin A included exposure to chicken pox (varicella), non-resolving otitis
      media, incomplete or no response and relapse. All side effects have resolved
      since the treatment was discontinued. Following discontinuation of cyclosporin A
      insulin requirements and glycated hemoglobin levels increased while glucagon
      stimulated connecting peptide levels declined dramatically.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1397783
TI  - The sympathetic response to euglycaemic hyperinsulinaemia. Evidence from
      microelectrode nerve recordings in healthy subjects.
AB  - Sympathetic nervous system activation by insulin has been suggested as a
      mechanism explaining the association between insulin resistance and hypertension.
      We further examined the effect of insulin by direct microneurographic muscle and
      skin nerve sympathetic activity recordings during euglycaemic insulin clamps in
      healthy subjects. The mean plasma insulin level was elevated from 5.3 +/- 0.7 to
      92.2 +/- 2.2 mU/l in seven subjects during a 90-min one-step clamp. In six other
      subjects plasma insulin was further raised from 85.7 +/- 4.0 mU/l to 747 +/- 53
      mU/l between 45-90 min (two-step clamp). Four of the latter subjects received a
      sham clamp with NaCl infusions only on a second recording session. At the low
      dose of insulin muscle nerve sympathetic activity increased from a resting level
      of 22.7 +/- 5.0 bursts per min to 27.7 +/- 5.0 bursts per min at 15 min (p less
      than 0.05). The increases in muscle nerve sympathetic activity were significant
      (p less than 0.001; ANOVA) throughout insulin infusion, with a slight further
      increase (from 29.2 +/- 1.6 to 32.3 +/- 1.9 bursts per min) at the
      supraphysiological insulin concentration. During sham clamps muscle nerve
      sympathetic activity did not increase. Both insulin clamps induced minor, but
      significant, increases in forearm venous plasma noradrenaline concentrations.
      Skin nerve sympathetic activity (n = 3) did not change during insulin infusions.
      Heart rate increased slightly but significantly (p less than 0.005), during the
      insulin clamps. Blood pressure was not notably affected. In conclusion,
      hyperinsulinaemia was associated with increased vasoconstrictor nerve activity to
      skeletal muscle and with no change of sympathetic outflow to skin.

PMID- 1397786
TI  - Immunohistochemical measurements of nerves and neuropeptides in diabetic skin:
      relationship to tests of neurological function.
AB  - Image-analysis was used to measure nerves immunoreactive to the general neuronal
      marker protein gene product 9.5 (PGP 9.5-IR) and the neuropeptides calcitonin
      gene-related peptide and vasoactive intestinal polypeptide in standardised leg
      skin biopsies of three age-matched groups of young subjects: non-diabetic (n =
      14), diabetic patients with normal small fibre function ("non-neuropathic", (n =
      11) and diabetic patients with abnormal small fibre function ("neuropathic", n =
      11). Depletion of nerves and neuropeptides was most marked in the epidermis,
      where calcitonin gene-related peptide-immunoreactivity was more frequently absent
      than PGP 9.5-IR in diabetic patients. Epidermal PGP 9.5-IR nerve area and counts
      were reduced in neuropathic compared with normal subjects (p less than 0.001), as
      were epidermal calcitonin gene-related peptide nerve counts (p = 0.003). Sweat
      gland PGP 9.5 and vasoactive intestinal polypeptide, which may be involved in
      sweat production, showed no diminution in diabetic patients (area: p = 0.160, p =
      0.372 by ANOVA). Two diabetic patients showed elevated sweat gland PGP 9.5-IR and
      three had increased sweat gland vasoactive intestinal polypeptide; this may
      represent nerve proliferation. In local sweat tests, acetylcholine-stimulated
      sweat output was associated with increased immunoreactivity, while the
      sympathetic skin response showed inverse correlations with immunoreactivity.
      There were no consistent changes with other commonly-used neurophysiological
      tests. HbA1 correlated negatively with immunohistochemical measurements.
      Neuropeptide changes were seen in the absence of macro- and microvascular
      disease, and epidermal nerve depletion occurred in patients with normal thermal
      thresholds and cardiac autonomic function.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397788
TI  - Hypomagnesaemia and type 2 (non-insulin-dependent) diabetes mellitus.

PMID- 1397787
TI  - Cognitive function in type 1 (insulin-dependent) diabetic patients after
      nocturnal hypoglycaemia.
AB  - Eight Type 1 (insulin-dependent) diabetic patients with no diabetic complications
      were studied on two consecutive and one subsequent overnight occasions. The aim
      was to evaluate the influence of nocturnal hypoglycaemia on neuropsychological
      and reaction time tests the following morning. Hypoglycaemia was induced by i.v.
      insulin infusion, blood glucose nadir was 1.5 +/- 0.3 mmol/l. Duration of
      hypoglycaemia (blood glucose less than 3 mmol/l) was 101 +/- 38 min. Whole night
      sleep statistics for all patients showed no statistical differences between the
      normoglycaemic and hypoglycaemic nights, however, there was a tendency of
      prolongation of the second sleep cycle in the nights with hypoglycaemia. Each
      patient was used as his own control and periods with blood glucose concentration
      less than 3 mmol/l were compared to exactly the same periods in nights with blood
      glucose level over 5 mmol/l. During hypoglycaemia the amount of deep sleep was
      reduced and replaced by superficial sleep and arousals of short duration.
      Further, the reduction in deep sleep was replaced later at night.
      Neuropsychological test scores and reaction time measurements in the morning
      showed no differences between the normoglycaemic and hypoglycaemic nights. IN
      CONCLUSION: despite sleep disturbances, nocturnal hypoglycaemia did not impair
      cognitive function the following morning in Type 1 (insulin-dependent) diabetic
      patients.

PMID- 1397789
TI  - In vitro percutaneous absorption of cadmium from water and soil into human skin.
AB  - The objective was to determine percutaneous absorption of cadmium as the chloride
      salt from water and soil into and through human skin. Soil (Yolo County 65
      California-57-8) was passed through 10-, 20-, and 48-mesh sieves. Soil retained
      by 80 mesh was mixed with radioactive cadmium-109 at 13 ppb. Water solutions of
      cadmium-109 at 116 ppb were prepared for comparative analysis. Human cadaver skin
      was dermatomed to 500-microns, and used in glass diffusion cells with human
      plasma as the receptor fluid (3 ml/hr flow rate) for a 16-hr skin application
      time. Cadmium in water (5 microliters/cm2) penetrated skin to concentrations of
      8.8 +/- 0.6 and 12.7 +/- 11.7% of the applied dose from two human skin sources.
      Percentage doses absorbed into plasma were 0.5 +/- 0.2 and 0.6 +/- 0.6%,
      respectively. Cadmium from soil (0.04 g soil/cm2) penetrated skin at
      concentrations of 0.06 +/- 0.02 and 0.13 +/- 0.05% for the two human skin
      sources. Amounts absorbed into plasma were 0.01 +/- 0.01 and 0.07 +/- 0.03%. Most
      of the nonabsorbed cadmium was recovered in the soap and water skin surface wash.
      Binding of cadmium from water to soil was greater than binding from water to
      powdered human stratum corneum, supporting the lower absorption from soil than
      from water. Short-term exposure of cadmium in water to human skin for 30 min
      (bath or swim) resulted in skin uptake, which upon further perfusion (48 hr),
      absorbed into the plasma receptor fluid (systemic). Cadmium in soil was increased
      from 6.5 to 65 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397790
TI  - Effects of a GnRH agonist on fertility following administration to prepubertal
      male and female rats.
AB  - Leuprolide, a GnRH agonist, was administered daily to male and female rats for 90
      days. Animals were sexually immature (25 days old) at the outset. Dosages were 20
      and 200 micrograms/kg/day. Five males and five females were euthanized on Day 91.
      Sex organs were weighed and evaluated for histopathologic changes. These
      procedures were repeated 140 days later. Following a recovery period lasting 45
      days (onset of normal-appearing estrous cycles) in females and 140 days (two
      spermatogenic cycles) in males, the fertility of these rats was assessed by
      mating with untreated animals. Treated males gained less weight while treated
      females gained more weight than controls. Weights of primary and secondary sex
      organs were reduced below control, but returned to normal following 140 days of
      recovery. Treated males were fertile and produced normal litters. Reproductive
      performance of low-dosage (20 micrograms/kg/day) females was normal 45 days after
      treatment cessation, but half of the high-dosage (200 micrograms/kg/day) females
      failed to become pregnant. However, reproductive performance of this group
      compared well with control performance after an additional 6 weeks of recovery.
      Atrophic changes were noted in male and female sex organs. Following 140 days of
      recovery, ovaries, uterus, vagina, prostate, and seminal vesicle were normal.
      Although testes and epididymides showed partial recovery at this time, multifocal
      or segmental atrophy and mineralization were noted in portions of some
      seminiferous tubules.

PMID- 1397791
TI  - Quantitative plasma disposition of retinol and retinyl esters after high-dose
      oral vitamin A administration in the cynomolgus monkey.
AB  - A solid-phase extraction technique followed by automated high-performance liquid
      chromatography sample elution was successfully used to evaluate the effect of
      three pharmaceutical parameters on the plasma profile of various forms of vitamin
      A after an oral dose to cynomolgus monkeys. The three parameters evaluated were
      the chemical form of vitamin A (retinol versus retinyl acetate), the vehicle
      (acetone/Tween 20/water versus acetone/soybean oil), and the retinol dose (2, 10,
      and 50 x 10(3) retinol equivalents/kg). The form of the administered compound,
      retinol or retinyl acetate, appeared to have no major effect on the formation of
      nonpolar retinoids. The ester profile in plasma differed depending on whether the
      dose was administered in the water-based or the oil-based vehicle. Irrespective
      of the vehicle type the predominant retinoid formed was retinyl palmitate/oleate.
      However, retinol doses in the water-based vehicle formed relatively high
      concentrations of retinyl laurate and retinyl myristate but no retinyl
      linolenate. The retinol dose in the oil-based vehicle formed consistent, but
      relatively minor, concentrations of retinyl linolenate, higher relative
      concentrations of retinyl linoleate, and no retinyl laurate or myristate. The
      dose of retinol administered had an impact on the diversity of the nonpolar
      retinoid profile. The low dose led to the presence of almost exclusively retinyl
      palmitate/oleate and retinyl stearate, whereas at higher doses the other retinyl
      esters became major retinol constituents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397792
TI  - Acute respiratory effects of endotoxin-contaminated machining fluid aerosols in
      guinea pigs.
AB  - Exposure to machining fluid aerosols in the automotive industry is associated
      with a variety of respiratory symptoms including cross-shift changes in pulmonary
      function, cough, asthma, and phlegm. Lubricating and cooling fluids used in
      machining operations are predominantly water and thus are susceptible to
      microbial growth. In the present study, the role of endotoxin in the acute
      pulmonary injury produced by machining fluid aerosols was examined in guinea
      pigs. Animals were exposed to nebulized water, unused machining fluid, or used
      machining fluid. At the end of a 3-hr exposure, specific airway conductance
      (SGaw) was not affected by exposure to the vehicle water, but was decreased in a
      dose-dependent manner by exposure to aerosols of the used machining fluid. SGaw
      decreased from preexposure baseline values by 0, 7, and 40% in animals exposed to
      1, 10, and 100 mg/m3 used machining fluid, respectively. These exposure levels
      also produced acute lung injury as evidenced by changes in cellular and
      biochemical indices in lavage fluid. These adverse respiratory effects may have
      been due to microbial contamination of the used machining fluid as the aerosol
      exposures were associated with airborne endotoxin concentrations of 0.3, 1.9, and
      5.3 micrograms/m3, respectively. Animals exposed to aerosols of the endotoxin
      free unused machining fluid had no statistically significant adverse functional,
      cellular, or biochemical effects except for a fourfold increase in neutrophils at
      100 mg/m3. These results suggest that contamination of machining fluid during use
      or storage may lead to the adverse respiratory effects of aerosolized machining
      fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397793
TI  - Effect of dose on the disposition of methoxyethanol, ethoxyethanol, and
      butoxyethanol administered dermally to male F344/N rats.
AB  - The glycol ethers methoxyethanol (ME), ethoxyethanol (EE), and butoxyethanol (BE)
      are widely used in industrial and household products. Rodent studies indicate the
      ME and EE are potentially toxic compounds causing teratogenic, fetotoxic,
      hematotoxic, and testicular effects. Exposure of rodents to high concentrations
      of BE resulted in anemia due to hemolysis of blood cells, leukopenia,
      hemoglobinuria, and liver and kidney damage. The purpose of this study was to
      determine the uptake, metabolism, and excretion of dermally administered glycol
      ethers as a function of the externally applied dose. Three different amounts of
      the 14C-labeled glycol ethers (450-4000 mumole/kg) were applied to same-sized
      areas on the clipped backs of F344/N rats, and nonoccluded percutaneous
      absorption was measured. The rates of excretion of the 14C-labeled parent
      compound and metabolites by different routes were measured, as well as the amount
      of 14C remaining in the carcass. Within the dose range studied, the absorption
      and metabolism of these three glycol ethers by F344/N rats was linearly related
      to the dermally applied dose. The absorption of all three glycol ethers was
      approximately 20-25%, regardless of the chain length of the alkyl group or the
      dose administered. The majority of the absorbed dose was excreted in the urine.
      Feces and exhaled CO2 represented minor routes of excretion. The alkoxyacetic
      acid was a major metabolite for all three glycol ethers. The formation of small
      amounts of ethylene glycol indicated cleavage of the ether bond.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1397794
TI  - Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke
      from a reference cigarette. I. Inhalation toxicology and histopathology.
AB  - Sprague-Dawley rats were exposed 6 hr per day for 14 consecutive days to aged and
      diluted sidestream smoke (ADSS), used as a surrogate for Environmental Tobacco
      Smoke (ETS), at concentrations of 0.1 (typical), 1 (extreme), or 10 (exaggerated)
      mg of particulates per cubic meter. Animals were exposed nose-only, inside whole
      body chambers, to ADSS from the 1R4F reference cigarette. End-points included
      histopathology, CO-oximetry, plasma nicotine and cotinine, clinical pathology,
      and organ and body weights. The only pathological response observed was slight to
      mild epithelial hyperplasia and inflammation in the most rostral part of the
      nasal cavity, in the high-exposure group only. No effects were noted at medium or
      low exposures. The minimal changes noted were reversible, using a subgroup of
      animals kept without further treatment for an additional 14 days. Overall, the
      end-points used in the study demonstrated that there was no detectable biological
      activity of ADSS at typical or even 10-fold ETS concentrations and that the
      activity was only minimal at very exaggerated concentrations (particle
      concentrations 100 times higher than typical real-world concentrations).

PMID- 1397796
TI  - Sequential study in rats of nasal and hepatic lesions induced by N
      nitrosodimethylamine and N-nitrosopyrrolidine.
AB  - Female Sprague-Dawley rats were given an ip dose of N-nitrosodimethylamine (NDMA)
      and N-nitrosopyrrolidine (NPYR), singly or in combination, and the sequential
      development of lesions in the liver and nasal cavity was characterized. Liver and
      nasal tissues were collected from rats given either NDMA or NPYR and killed at 6
      or 12 hr and 1, 3, 10, or 30 days. After combination exposure, rats were killed
      at 3 or 30 days. Olfactory epithelium and adjacent Bowman's glands were
      specifically targeted by each chemical. Lesions were seen as early as 6 hr and
      were most severe by 3 days. At the high doses (60 mg/kg NDMA or 100 mg/kg NPYR)
      regeneration was not complete by 30 days. Hepatic necrosis was seen at 1 and 3
      days with NDMA but was not seen with NPYR. Combination exposure appeared to cause
      additive effects in both the liver and the nasal cavity. Results indicate that a
      single ip administration of NDMA or NPYR can induce severe and prolonged toxic
      effects on nasal tissues in rats.

PMID- 1397795
TI  - Fourteen-day inhalation study in rats, using aged and diluted sidestream smoke
      from a reference cigarette. II. DNA adducts and alveolar macrophage cytogenetics.
AB  - The chemical constituents of cigarette smoke are greatly diluted in environmental
      tobacco smoke (ETS). In the typical indoor environment where cigarettes are
      smoked, the mean value of respirable suspended particles is approximately 0.1
      mg/m3. In this study, we used aged and diluted sidestream smoke (ADSS) of 1R4F
      University of Kentucky research cigarettes as a surrogate for ETS and exposed
      Sprague-Dawley rats nose-only to 0, 0.1, 1.0, and 10 mg wet total particulate
      matter (WTPM)/m3 for 6 hr per day for 14 consecutive days. DNA from lung, heart,
      larynx, and liver was tested for adduct formation after 7 and 14 days of exposure
      and after 14 days of recovery. In addition, alveolar macrophages from animals
      exposed for 7 days were examined for chromosomal aberrations. Exposure-related
      DNA adducts were not observed in any of the animals at 0.1 or 1.0 mg WTPM/m3,
      which represent ambient and 10-fold exaggerated ETS concentrations, respectively.
      Slight diagonal radioactive zones, characteristic of adducts observed in human
      smokers and in animals exposed to mainstream smoke, were observed, but only in
      lung and heart DNA of animals exposed to the highest concentration of ADSS (10 mg
      WTPM/m3), a 100-fold exaggeration of typical field measurements of ETS. The mean
      relative adduct labeling values (+/- SE) were 8.7 (+/- 0.2) adducts per 10(9)
      nucleotides for lung DNA and 5.7 (+/- 0.7) adducts per 10(9) nucleotides for
      heart DNA after 14 days of exposure. No elevation in chromosomal aberrations was
      observed in alveolar macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397797
TI  - The developmental toxicity of ethylene glycol diethyl ether in mice and rabbits.
AB  - Timed-pregnant CD-1 outbred Albino Swiss mice and New Zealand White rabbits were
      dosed by gavage with ethylene glycol diethyl ether (EGdiEE) in distilled water
      during major organogenesis. Mice were dosed on Gestational Days (gd) 6 through 15
      (0, 50, 150, 500, or 1000 mg/kg/day) and rabbits on gd 6 through 19 (0, 25, 50,
      or 100 mg/kg/day). Maternal clinical status was monitored daily during treatment.
      At termination (gd 17, mice; gd 30, rabbits), confirmed-pregnant females (22-24
      per group, mice; 26-32 per group, rabbits) were evaluated for clinical status and
      gestational outcome; each live fetus was examined for external, visceral, and
      skeletal malformations. In mice, no maternal mortality was observed, but maternal
      body weight gain during gestation and treatment, and at termination was reduced
      at 1000 mg/kg/day. The reduction of maternal body weight gain during gestation
      was secondary to embryo/fetal toxicity, i.e., reduced gravid uterine weight as a
      consequence of decreased litter size and fetal weight. The no-observed adverse
      effect level (NOAEL) for developmental toxicity was 50 mg/kg/day. At greater than
      or equal to 150 mg/kg/day the number of litters of mice with malformed fetuses
      was increased. At greater than or equal to 500 mg/kg/day fetal body weight was
      reduced, and malformation incidence was significantly increased. Exencephaly and
      fused ribs were observed most often. In rabbits, maternal body weight was
      unaffected by treatment even though 6% maternal mortality was observed at 100
      mg/kg/day. The developmental NOAEL was 25 mg/kg/day. Malformations were increased
      at greater than or equal to 50 mg/kg/day; short tail, small spleen, fused
      sternebrae, and fused rib cartilage were observed most often. In summary, oral
      administration of EGdiEE to mice and rabbits during organogenesis produced
      profound adverse developmental effects even in the absence of significant
      maternal toxicity. Developmental effects in rabbits were more varied.

PMID- 1397798
TI  - Mouse ear swelling test (MEST)

PMID- 1397799
TI  - Reproductive and developmental toxicity of N,N-diethyl-m-toluamide in rats.
AB  - N,N-Diethyl-m-toluamide (mDET, DEET) is widely used as a topical insect
      repellent. It is the active ingredient in many consumer formulations, which
      usually contain 10-25% mDET in an alcohol base. More concentrated consumer
      products are also available, including some that are pure technical grade mDET.
      Persons living or employed in mosquito-infested areas may have very high seasonal
      exposures to mDET. Because contradictory reports had been published on the
      reproductive and developmental toxicity of mDET, a series of studies was
      conducted in male and female Sprague-Dawley rats. All treatments were
      administered by daily subcutaneous injections of undiluted mDET. A dose finding
      study was done using 12 time-mated females per group treated on Gestational Days
      (GD) 6-15 with 0.50, 0.62, 0.78, 0.92, or 1.2 ml mDET/kg/day. No females survived
      10 days of mDET dosing with 1.2 ml/kg/day. Deaths occurred in all other groups
      except the low dose (0.50 ml/kg/day). Pregnant females treated on GD 6-15 with 0
      or 0.30 ml/kg/day were used for the teratology study. Half of each group was
      euthanized on GD 20: the second half was singly housed in nesting boxes and
      allowed to deliver litters. Live pups were counted and weighed soon after birth
      on Postnatal Day (PD) 0 and again on PD 3, 9, and 14. Proven fertile males were
      treated 5 days/week for 9 weeks with 0, 0.30, 0.73, 1.15, or 1.80 ml mDET/kg/day
      for a male dose-finding study. Each group consisted of 20 males. No males
      survived the 1.80 ml/kg/day. Deaths occurred in all remaining dose groups except
      the 0.30 ml/kg/day and control group. Immediately following the final treatment
      of the male dose study, 11 males were randomly selected from the 0.30 and 0.73
      ml/kg/day groups. They were cohabited for 7 days with 4 females per male during
      post-treatment Weeks 1 and 2. Half of the females were euthanized 12-14 days
      after the last day of cohabitation for a dominant lethal study; the remaining
      females were singly housed in nesting boxes and allowed to deliver litters. Live
      pups were counted and weighted on PD 0 and 3. There was no evidence of
      reproductive or developmental toxicity in any of these assays, but there were
      signs of neurotoxicity in treated adult male and female rats, which may relate to
      reports of neurotoxicity in humans heavily exposed to mDET-containing insect
      repellents.

PMID- 1397801
TI  - Effect of p-xylene inhalation on the bioactivation of bromobenzene in rat lung
      and liver.
AB  - It is unclear whether the pneumotoxicity observed with bromobenzene (BB) in
      phenobarbital-induced rats is related to BB bioactivation in lung, liver or both.
      To help differentiate pulmonary from hepatic bioactivation, BB was administered
      alone and in combination with p-xylene, which inhibits pulmonary but induces
      hepatic cytochromes P450. Exposure to p-xylene alone (3400 ppm for 4 hr) produced
      no changes in bronchoalveolar lavage fluid (BALF) measurements (gamma-glutamyl
      transpeptidase, lactate dehydrogenase, protein, white blood cell count) or serum
      sorbitol dehydrogenase. p-Xylene increased hepatic microsomal benzyloxy- (BROD),
      pentoxy- (PROD), and ethoxy- (EROD) resorfuin O-dealkylase activities but
      decreased pulmonary microsomal BROD and PROD. Immunoblot analysis revealed an
      induction of hepatic but not pulmonary microsomal P450IIB apoprotein. When rats
      were exposed to p-xylene (2800 ppm) or room air for 4 hr, treated 12 hr later
      with BB (0.5 ml/kg, ip) or corn oil, and killed after 12 hr, p-xylene increased
      hepatic P450IIB (27-fold) concomittant with a similar increase in BROD activity.
      p-Xylene also increased hepatic P450IA apoprotein (3.4-fold) with a complimentary
      increase in EROD activity. p-Xylene potentiated BB-induced hepatotoxicity. In
      pulmonary microsomes p-xylene and BB each produced similar decreases in both EROD
      and BROD activities. The combination of p-xylene and BB had an additive effect on
      pulmonary P450IA1 reduction. BALF analysis and histopathology revealed no
      pneumotoxicity with any treatment. p-Xylene potentiation of BB-induced
      hepatotoxicity without pneumotoxicity suggests that the liver does not produce
      metabolites of BB which are directly involved in pulmonary damage.

PMID- 1397800
TI  - 1-Aminobenzotriazole-induced destruction of hepatic and renal cytochromes P450 in
      male Sprague-Dawley rats.
AB  - 1-Aminobenzotriazole (ABT) is a suicide substrate of both hepatic and pulmonary
      cytochromes P450. The present studies were designed to compare the effects of ABT
      on hepatic and renal metabolism. Hepatic and renal microsomes and cytosol were
      prepared from male Sprague-Dawley rats following ABT pretreatment (0-100 mg/kg
      ip) for various times. Administration of 100 mg ABT/kg produced profound
      reductions in P450 content in both liver and kidney within 2 hr; loss of P450 in
      both tissues persisted for at least 48 hours. ABT-induced destruction of P450 was
      dose-dependent. Maximal destruction of about 80% of total hepatic P450 occurred
      at dosages of ABT equal to or greater than 10 mg/kg. Maximal destruction of about
      80% of total renal P450 occurred at dosages of ABT equal to or greater than 50
      mg/kg. In vitro, ABT rapidly and efficiently destroyed P450 in both hepatic and
      renal microsomes prepared from naive male Sprague-Dawley rats. Incubation of
      hepatic or renal microsomes in vitro with ABT produced detectable destruction of
      P450 within 5 min. Maximal destruction of P450 occurred within 10 min in both
      hepatic and renal microsomes during in vitro incubation with ABT. ABT-induced
      destruction of P450 in vitro was concentration-dependent. For hepatic microsomes,
      maximal destruction of about 70% of P450 required concentrations of ABT equal to
      or greater than 10 mM. For renal microsomes, maximal destruction of about 80% of
      P450 required concentrations of ABT equal to or greater than 10 mM. In both liver
      and kidney, only P450 content and P450-dependent activities were significantly
      decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397802
TI  - Adverse male reproductive effects following subchronic exposure of rats to sodium
      dichloroacetate.
AB  - Dichloroacetate (DCA) activates the pyruvate dehydrogenase complex enhancing
      carbohydrate and lactate utilization in animals. As a result it is used
      clinically in the treatment of acute lactic acidosis and has therapeutic
      potential in the treatment of stroke. Adverse effects of chronic DCA treatment
      include polyneuropathy and testicular degeneration. Since DCA is a principal
      product of the aqueous chlorination of fulvic acids concern has arisen regarding
      the agent's impact on environmental health. We treated male Long-Evans rats with
      0, 31.25, 62.5, or 125 mg DCA/kg/day by oral gavage for 10 weeks. Compared to
      controls, preputial gland and epididymis weights were reduced at 31.25 mg/kg,
      body and liver weights at 62.5 mg/kg, and accessory organ weights at 125 mg/kg.
      Epididymal sperm counts were reduced and sperm morphology was impacted at the
      62.5 and 125 mg/kg doses levels. Histologic examination of the testis and
      epididymis revealed inhibited spermiation in testes at the 125 mg/kg dose level.
      Computer-assisted sperm motion analysis revealed reductions in percentage motile
      sperm, curvilinear and straight-line velocity, linearity, and amplitude of
      lateral head displacement at both the 62.5 and the 125 mg/kg dose levels. In the
      assessment of fertility after an overnight mating, the number of viable implants
      on Day 14 of gestation was decreased only in the highest dose group. These
      studies demonstrate adverse effects of NaDCA treatment on the rat male
      reproductive system, primarily on the accessory organs and sperm within them at
      lower doses (31.25 and 62.5 mg/kg), and on the testis at the highest dose (125
      mg/kg).

PMID- 1397803
TI  - Chronic toxicity of the anticancer agent trimetrexate in rats.
AB  - Trimetrexate was administered to rats in an interrupted treatment regimen
      comparable to proposed human clinical treatment. Forty-five rats of each sex were
      dosed intravenously with trimetrexate at 0, 1, 10, or 30 mg/kg (0, 6, 60, or 180
      mg/m2), once daily for 5 consecutive days, followed by a 23-day recovery period.
      This cycle of dosing and recovery was repeated for a total of six cycles.
      Hematology, urinalysis, clinical chemistry, and gross and microscopic pathology
      examinations were conducted for animals euthanatized 3 and 21 days after dosing
      cycles 1, 3, and 6. Additional rats in each group were maintained without dosing
      for an additional 56 days (77 days after the last trimetrexate dose) to assess
      the long-term reversibility of pathologic changes. Target organs were typical for
      an antifolate and included gastrointestinal tract, lymphoid tissues, and the
      hematopoietic and male reproductive systems. No toxicity was observed at 1 mg/kg.
      Treatment-related changes in hematology parameters following 10 and 30 mg/kg were
      fully reversible within 3 weeks of each dosing cycle. Except for testis and
      cecum, histopathological changes were also reversible within 21 days of dosing.
      Trimetrexate-induced testicular changes persisting during the course of multiple
      cycles of dosing were not reversible within 21 days, but required an additional
      56 days for essentially complete recovery.

PMID- 1397804
TI  - Noninvasive measurement of blood pressure in conscious cynomolgus monkeys.
AB  - Systolic (SP), diastolic (DP), and mean arterial blood pressures (MAP) and pulse
      rate (PR) were recorded on treated and untreated conscious cynomolgus monkeys by
      the oscillometric method (Dinamap 1846SX/P). Each monkey was placed in a
      restraining tube with the cuff placed on the base on the shaved tail.
      Measurements were taken on untreated animals once or twice a day for 4 weeks. The
      mean and standard deviations for SP, DP, MAP, and PR were approximately 121 +/-
      17, 60 +/- 14, and 84 +/- 17 mm Hg and 193 +/- 18 pulses/min, respectively. One
      male and one female cynomolgus monkey were treated with isoproterenol,
      norepinephrine, and nitroprusside. Blood pressure was measured indirectly with
      the cuff on the tail and directly with an indwelling catheter in the descending
      thoracic aorta. Although the oscillometric method was not as sensitive as the
      catheter, the oscillometric method detected a change in the same direction of SP,
      DP, MAP, and PR compared with the direct method for all drugs administered. The
      monitor was reliable and sufficiently accurate to conclude that it may be useful
      in toxicology studies for evaluation of blood pressure parameters in conscious
      cynomolgus monkeys.

PMID- 1397805
TI  - Toxicity of calcium sodium metaphosphate fiber. I. In vitro and in vivo
      degradation and clearance studies.
AB  - In an experiment to ascertain the degradability of calcium sodium metaphosphate
      (CSM) fiber in vitro, 32P-labeled CSM fiber was incubated in media with or
      without rat lung epithelial cells (LEC) or rat alveolar macrophages (RAM). The
      amount of radioactivity appearing in the filtrate of the media in the presence of
      cells minus the radioactivity in the media in the absence of cells was considered
      to reflect cell-aided dissolution of the fiber. LEC and RAM cells increased the
      degree of dissolution two- and sevenfold, respectively, compared to their
      respective media controls in a 7-day time period. In a separate experiment, male
      Fischer rats were given 32P-labeled CSM fiber either by intraperitoneal injection
      or by intratracheal instillation and the amount of radioactivity appearing in the
      urine and feces was measured over a period of 60 days. Selected animals from this
      experiment were also subjected to whole-body autoradiography 0, 1, 5, 15, 30, and
      60 days postexposure. After intraperitoneal injection, approximately 0.9% of the
      administered dose appeared in the urine. A similar percentage of the dose was
      eliminated in the urine when the fibers were administered by intratracheal
      instillation; however, the amount of radioactivity in the feces after
      intratracheal instillation, i.e., 11.6% of the administered dose, was much higher
      than that after intraperitoneal dose, i.e., 0.24% of the administered dose. Whole
      body autoradiographs showed a time-related increase in radioactivity at a site
      other than the site of administration, and the location of this radioactivity
      appeared to be exclusively associated with mineralized tissue. The clearance of
      nonradiolabeled CSM fiber (approximately 200,000 fibers) from rat lung after
      intratracheal inhalation (IH) and intratracheal instillation (IT) was monitored.
      Approximately 93% of the initial fiber load after IH and approximately 84% of the
      initial fiber load after IT was cleared from the lung in 6 months. Histological
      and biochemical evaluation of the rat lungs did not reveal any indication of
      fibrosis up to a period of 6 months. All the studies discussed indicate that CSM
      is degradable in biological systems and is cleared from the lung after IT and IH
      administration. These attributes of CSM fiber should reduce the potential for
      chronic adverse effects in the lung after inhalation.

PMID- 1397806
TI  - Toxicity of calcium sodium metaphosphate fiber. II. Chronic inhalation and
      oncogenicity study.
AB  - Male and female Fischer 344 rats (80/sex/group) were exposed to CSM fiber 6
      hr/day, 5 days/week at target-exposure levels of 0, 1, 5, or 25 mg/m3 for 24
      months, corresponding to 0, 27, 80, and 513 fibers/cc, respectively. Number and
      size of the airborne fibers were determined during the course of the study. At 3
      and 12 months, 10 rats/sex/group were euthanized and at 18 and 24 months 5
      rats/sex/group were euthanized. In addition, 5 rats/sex/group were removed from
      exposure at 18 months and maintained for a 6-month recovery period. All animals
      surviving at the completion of the exposure period were maintained in a clean
      environment for up to 5 additional months. Clinical laboratory examinations were
      performed on 10 animals/sex/group at 3, 12, and 24 months. The number of fibers
      in the lung were also determined at 3, 12, 18, and 24 months. Body weight and
      survival did not appear to be affected by treatment. There were no biologically
      significant effects on clinical parameters. There was a dose-related increase in
      lung weight during the exposure period which was generally reversible during the
      recovery periods. There also was a dose-related increase in the number of
      fibers/milligram of lung, but no increase in lung fiber burden after the first 3
      months. The number of fibers in the lungs of animals exposed to CSM fiber for 18
      months and allowed 6-month recovery period showed a decrease especially at the
      high dose. No increase in tumors (benign or malignant) was observed in this
      study. Microscopic changes considered reflective of an irritant response were
      observed in the nasal turbinates notably at the 5 and 25 mg/m3 levels.
      Histological changes were also observed in the lungs at the 5 and 25 mg/m3
      levels. The incidence and/or severity of histopathological changes in the 1 mg/m3
      group was considered to be essentially comparable to controls.

PMID- 1397809
TI  - Pregnancy care problems in the rural southeast.

PMID- 1397808
TI  - A benzodiazepine sketch of a war.

PMID- 1397807
TI  - Subchronic toxicity studies of t-butyl alcohol in rats and mice.
AB  - The purpose of this study was to evaluate the toxicity of t-butyl alcohol, an
      important commodity chemical, an additive to unleaded gasoline, and a contaminant
      of drinking water. Ninety-day toxicity studies were conducted in B6C3F1 mice and
      Fischer 344 (F344) rats of both sexes using dosed water. Dose levels of t-butyl
      alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v). Lethality was observed at the 4%
      level of both sexes and species. Weight-gain depression was present in all dose
      levels of male rats; 4% female rats; 1, 2, and 4% male mice; and 2 and 4% female
      mice. Water consumption was increased at lower dose levels in male rats and
      decreased in the higher dose levels of both sexes of rats and female mice.
      Clinical signs in rats were ataxia in both sexes and hypoactivity in males.
      Clinical signs in mice were ataxia, abnormal posture, and hypoactivity. In rats,
      urine volumes were reduced, in association with crystalluria. Gross lesions at
      necropsy were urinary tract calculi, renal pelvic and ureteral dilatation, and
      thickening of the urinary bladder mucosa. Microscopic lesions were hyperplasia of
      transitional epithelia and inflammation of the urinary bladder. In male rats
      treated with t-butyl alcohol, microscopic renal changes were suggestive of alpha
      2 mu-globulin nephropathy. No-effect levels for the urinary tract lesions were 1%
      in male rats and mice (803.7 mg/kg/day for the male rats and 1565.8 mg/kg/day for
      the male mice) and 2% in female rats and mice (1451.5 mg/kg/day for the female
      rats and 4362.9 mg/kg/day for the female mice). The results indicate that in
      rodents the urinary tract is the target organ for t-butyl alcohol toxicity, and
      males are more sensitive to t-butyl alcohol toxicity than females.

PMID- 1397810
TI  - Establishing an academic department of family medicine at the Albert Einstein
      College of Medicine.

PMID- 1397811
TI  - A survey of formal training in the care of children in family practice residency
      programs.
AB  - BACKGROUND: Declining hospitalization rates for children and an increased
      emphasis on ambulatory care may be affecting the way family practice residency
      programs train their residents in the care of children. METHODS: We surveyed all
      US family practice residency program directors to determine the nature of the
      child care training that programs currently provide to residents. RESULTS:
      Responses were received from 78% of the programs. Residencies required a mean of
      5.2 months of formal pediatric training (range: 1 to 11 months). Thirty percent
      of programs noted a declining inpatient census on inpatient pediatric teaching
      services, but since 1978, the mean duration of inpatient pediatric training
      increased by 0.4 months to a required mean of 2.7 months of general pediatric
      inpatient training (range: 0 to 6 months). The mean time devoted to structured
      outpatient pediatric training was only 1.6 months (range: 0 to 6 months). Nine
      percent of responding programs required no formal pediatric outpatient training
      other than family health center experience. CONCLUSIONS: Despite declining
      inpatient census and increased emphasis on comprehensive ambulatory care, family
      practice residencies require more formal inpatient pediatric training than formal
      outpatient training.

PMID- 1397812
TI  - Policy recommendations for pharmaceutical representative-resident interactions.
AB  - Based on our review of existing written policies regarding pharmaceutical
      representative-resident interactions, we believe that residencies should develop
      more comprehensive policies. We present six topic areas that programs should
      address in formulating policies: 1) policy tone, 2) traffic control, 3) samples,
      4) gifts, 5) screening of educational and promotional materials and events, and
      6) honoraria, research funding, and other monetary exchanges.

PMID- 1397813
TI  - A survey method for investigating ethical decision making in family practice.
AB  - BACKGROUND: The tension between respect for patient autonomy versus concern for
      patient welfare is a challenging ethical issue for physicians. The purpose of
      this research was to describe a method for analyzing ethical decisions and to
      report the results of a survey of ethical decision making among family
      physicians. METHODS: We developed a survey instrument that used simulated case
      scenarios, each of which posed an ethical dilemma. The ethical problems on the
      survey included the extent to which diagnostic information should be revealed to
      patients, the extent to which physicians should become involved in patients' life
      style issues, and how to deal with patients' family problems. We mailed the
      questionnaire to 1,300 US family physicians. RESULTS: Six hundred seventy-four
      physicians responded. Respondents did not deal with the simulated ethical
      problems in a uniform manner and often tended to respond more to specific details
      of a case rather than the overall ethical dilemma posed. Physicians who chose a
      course of action giving patients more control were motivated by factors that
      showed respect for patient autonomy. On the other hand, physicians who chose a
      course of action giving patients less control were not motivated by factors
      suggesting a concern for patient welfare. CONCLUSIONS: Based on responses to
      simulated case scenarios, family physicians did not demonstrate a uniform
      approach but rather a more contextual one. Respect for patient autonomy was
      linked to family physicians' reported courses of action.

PMID- 1397814
TI  - A clinical trial to reduce the rate of low birth weight in an inner-city black
      population.
AB  - BACKGROUND: The goal of our study was to measure the effectiveness of a home
      based intervention for prevention of low birth weight with 154 high-risk, low
      income black women attending a prenatal clinic in Cleveland. METHODS: Based on
      previous research, risk was defined by clinic registration between the 17th and
      28th weeks of gestation, low family functioning score, and experience of at least
      one stressful life event prior to registration. Optional factors included being a
      smoker, a low maternal weight-height ratio, being age 27 or older, and a previous
      premature birth. A 21-item family function screen previously validated in a
      similar population was the primary determinant of psychosocial risk. Low birth
      weight was defined as weight less than 2,500 g regardless of gestational age.
      RESULTS: There was no decrease in the rate of low birth weight for women who
      received four home visits focusing on smoking, drug and nutrition education,
      support, and links with community services, compared to women who received no
      visits. The number of prenatal visits was significantly higher in the
      intervention group, but an increased number of prenatal visits did not correlate
      with a reduced rate of low birth weight. Despite previous research, the family
      function screen was not an effective predictor of low birth weight in our study.
      A revised equation involving a history of previous premature birth, smoking, and
      a low maternal weight-height ratio did predict low birth weight. CONCLUSIONS:
      These findings question the utility of short-term psychosocial interventions for
      influencing low birth-weight rates in low-income black clinic populations. The
      family function screen was not cross validated. Integration of any psychosocial
      intervention with the routine prenatal care occurring in the obstetrical clinic
      is suggested for future research.

PMID- 1397815
TI  - Inflammation on the cervical Papanicolaou smear: the predictive value for
      infection in asymptomatic women.
AB  - BACKGROUND: The clinical significance of inflammation on the cervical
      Papanicolaou (Pap) smear of asymptomatic women is unknown. This study assessed
      the possible association between inflammation on Pap smears with the presence of
      cervical/vaginal pathogens. METHODS: A questionnaire was given to 290
      asymptomatic women seen for routine gynecologic examination, including Pap smear,
      in a primary care setting. The women were tested for the presence of Candida
      species, Trichomonas vaginalis, Gardnerella vaginalis, Neisseria gonnorrhoeae,
      and Chlamydia trachomatis. RESULTS: Recovery of Chlamydia and Trichomonas was
      more frequent in women with inflammation on Pap smear than in women without
      inflammation, but the positive predictive value of inflammation was only 7% for
      Chlamydia and 14% for Trichomonas. Seventy-one percent of the women with
      inflammation had no evidence of any of the organisms. After a 6-month follow-up
      period, women with inflammation on Pap smear were no more likely than their
      matched counterparts without inflammation to return for a clinic visit with
      symptoms of vaginitis. CONCLUSIONS: In this study, inflammation on Pap smear had
      a relatively low predictive value for the presence of vaginal pathogens in
      asymptomatic women.

PMID- 1397816
TI  - Use of comprehensive geriatric assessment techniques by community physicians.
AB  - BACKGROUND: Research has shown that comprehensive assessment techniques have
      several clinical benefits for geriatric patients. The purpose of this study was
      to determine how frequently community practitioners used comprehensive geriatric
      assessment techniques to identify factors related to use of those techniques.
      METHODS: The study group included 54% of the 100 community-based family physician
      preceptors who participate in the University of Mississippi's family medicine
      training programs. On-site interviews were conducted in each physician's office
      to measure the percentage of physicians who performed comprehensive geriatric
      assessment. RESULTS: The majority of physicians employed some selected age
      related assessment techniques, but less than 25% performed functional assessment
      techniques considered unique to the geriatric patient, such as mental status
      assessment and evaluation of activities of daily living. Most physicians'
      personal and practice characteristics were unrelated to the use of assessment
      techniques. CONCLUSIONS: Although many physicians use some techniques of
      geriatric assessment, most practicing physicians do not perform comprehensive
      assessment of geriatric patients.

PMID- 1397817
TI  - From hospital to home: elderly patients' discharge experiences.
AB  - BACKGROUND: Little is known about the effect on elderly patients of the
      transition that occurs upon discharge from the hospital to the patients' homes.
      This report describes hospital discharge as experienced by a group of elderly
      patients. METHODS: Qualitative research techniques were used to study the effect
      of hospital discharge on 12 patients, 12 caregivers, and 62 health professionals
      involved in the process. Research methods included interviews, observation of
      participants, and review of pertinent documents. RESULTS: Findings indicate that
      the patients' mindsets and family relationships contribute to the discharge
      experience. Problems with communication among members of the health care team
      created problems in the discharge process. The opinions of health professionals
      and patients' family members sometimes differed regarding appropriateness of
      various facets of the discharge process. CONCLUSIONS: The findings suggest that
      there is a need to better facilitate communication and coordination of the
      hospital discharge process for elderly patients.

PMID- 1397818
TI  - Voices from family medicine: Theodore Phillips. Interview by William B. Ventres
      and John J. Frey.
AB  - Ted Phillips has had a remarkable career in medicine. He practiced in a rural
      Alaskan town, helped build the University of Washington's Department of Family
      Medicine as its founding chair, labored as an associate and acting dean at the
      university, and, more recently, returned to clinical practice part time on a
      small island in Washington state and travels to the University of Washington to
      direct the course on introduction to clinical medicine. Dr. Phillips was
      president of the Society of Teachers of Family Medicine in 1978-1979 and received
      the Society's Certificate of Excellence in 1981. He currently serves as the only
      community-based physician on the National Advisory Council of the Agency for
      Health Care Policy and Research. This transcript is an abridged version of
      interviews conducted in April and June 1992.

PMID- 1397819
TI  - The recruiting war.

PMID- 1397820
TI  - Increased substance abuse education.

PMID- 1397821
TI  - Resident recruiting.

PMID- 1397822
TI  - Guidelines on ethical recruitment of residents.

PMID- 1397823
TI  - Entry of US medical school graduates into family practice residencies: 1991-1992
      and 11-year summary.
AB  - This is the 11th report prepared by the American Academy of Family Physicians on
      the percentage of each medical school's graduates entering family practice
      residency programs. Approximately 10.3% of the 15,499 graduates of US medical
      schools between July 1990 and June 1991 were first-year residents in family
      practice in October 1991. This compares to 10.7% the previous year. The West
      North Central region reported the highest percentage of medical school graduates
      who were first-year residents in family practice programs in October 1991 at
      15.3%; the Middle Atlantic and New England regions continued with the lowest
      percentages. Graduates from publicly funded medical schools were more than twice
      as likely as those from privately funded schools to be first-year residents in
      family practice in October 1991, 12.9% compared to 6.2%. Approximately half of
      medical school graduates entering their first year of family practice residency
      training in October 1991 selected a program in the same state as their medical
      schools. This report includes the average percentage for each medical school for
      the last 11 years, as well as the number and percentage of graduates from
      osteopathic schools who entered ACGME-accredited family practice residency
      programs.

PMID- 1397824
TI  - Results of the 1992 National Resident Matching Program.
AB  - After 4 years of declining fill rates through the National Resident Matching
      Program (NRMP), 74 more positions in family practice residencies were filled in
      1992 than in 1991, including 24 more filled with US seniors. The March fill rate
      (67.5%) increased for the first time since 1987, while the July fill rate (90.7%)
      increased for the first time since 1984. The Mountain and Pacific regions had the
      highest fill rates (89.1% and 88.5%, respectively) through the NRMP. Community
      based, unaffiliated and university-affiliated programs filled 71.0% and 70.3% of
      positions offered through the NRMP. University-based and community-based,
      university administered programs filled 63.8% and 61.0% of positions offered
      through the NRMP. The other commonly defined primary care specialties of internal
      medicine and pediatrics also filled increased numbers of positions offered
      through the NRMP. This is the first year since 1984 in which all three primary
      care specialties matched more positions than in the previous year. The demand for
      family physicians in the United States is increasing. Evidence presented here
      suggests that 1992 may mark the beginning of a new trend toward increased
      interest in careers in family practice.

PMID- 1397825
TI  - Upper respiratory infection: stress, support, and the medical encounter.
AB  - BACKGROUND: The purpose of this study was to examine the relationship between
      stress and social support to behaviors of patients and physicians during an
      episode of upper respiratory infection (URI). METHODS: This was a cross-sectional
      study of 104 patients older than age 14 from three family practice sites; all of
      the patients had experienced a URI during an 8-week period. Stress scores were
      calculated for each patient's family using several standard instruments. Clinical
      and medical care utilization data were also reviewed. Data were analyzed to
      determine if there were relationships among stress and support scores and
      measures of patient and physician behaviors. RESULTS: Measures of stress and
      support were related to the use of medical services, seeking additional medical
      care, extra phone calls, and longer perceived duration of illness. Physicians
      prescribed more medications, ordered more laboratory tests, and scheduled more
      return visits for patients with high stress or low support scores. CONCLUSIONS:
      Stress and support are related to patient utilization of health services and
      perception of illness severity. Physicians respond to patients with high stress
      and low support by offering more medical services.

PMID- 1397826
TI  - Prescribing behaviors of family physicians in the treatment of osteoarthritis.
AB  - BACKGROUND: Patients with osteoarthritis are frequently managed by family
      physicians. New evidence suggests that nonsteroidal anti-inflammatory drugs
      (NSAIDs) are no more effective than simple analgesics for treating
      osteoarthritis. The purpose of this study was to characterize the pharmacologic
      prescribing practices of family physicians for treatment of osteoarthritis.
      METHODS: One hundred eleven Indian family physicians were asked to provide their
      initial treatment recommendations for a hypothetical patient who had
      uncomplicated osteoarthritis. Responses were analyzed and subsequently validated
      by an audit of actual cases managed by family physicians. RESULTS: The response
      rate was 78%. Of those responding, 97% chose NSAIDs as their first line of
      therapy. Physicians were more than twice as likely to use anti-inflammatory doses
      of these agents as they were to use analgesic doses. There were no significant
      differences between the results of the written simulation and the actual case
      audit (P = .4216). CONCLUSIONS: Family physicians generally treat osteoarthritis
      with NSAIDs, and they prescribe anti-inflammatory doses more than twice as often
      as analgesic doses. An audit of the actual practice behaviors of family
      physicians corroborated this prescribing pattern. This prescribing behavior may
      be inappropriate given evidence that simple analgesics are as effective as
      NSAIDs.

PMID- 1397828
TI  - Short-term training in geriatrics: an alternative for family medicine?
AB  - BACKGROUND: Family medicine has responded to the need for training in geriatrics
      by creating geriatric fellowships and by including geriatric education in
      residency and medical school curricula. Fellowships, in particular, require
      extensive time commitment by participating physicians. METHODS: We developed a 1
      month geriatric training experience for academic family physicians. We surveyed
      previous participants in this short course to determine their subsequent level of
      activity in geriatrics, whether they had become certified in geriatrics, and
      other information about their academic experience in geriatrics. RESULTS: Eighty
      one percent of graduates of this 1-month course had passed the geriatrics
      certification examination, compared to only 56% nationally. Graduates of the
      program were active as geriatric program directors and teachers of geriatrics,
      but there was limited activity in research or other scholarly activities related
      to geriatrics. CONCLUSION: Intensive short-term training in geriatrics meets some
      but not all of the needs for academic competency and productivity in geriatrics.

PMID- 1397827
TI  - The effect of a medical journal club on residents' knowledge of clinical
      epidemiology and biostatistics.
AB  - BACKGROUND: We performed a prospective controlled trial of a monthly journal club
      to determine if it would increase pediatric residents' knowledge of clinical
      epidemiology and biostatistics. METHODS: Intervention residents received two
      didactic sessions before the journal club started. Eight monthly journal club
      sessions followed. Pediatric residents at another institution served as controls.
      Intervention and control residents completed a pre- and post-test on clinical
      epidemiology and biostatistics. RESULTS: Neither the intervention nor the control
      group showed a significant change in test scores over the 9-month period.
      CONCLUSION: A more intensive and more structured approach is needed to
      effectively teach clinical epidemiology and biostatistics to residents.

PMID- 1397829
TI  - Health promotion/disease prevention in family practice residency training:
      results of a national survey.
AB  - BACKGROUND: Patient screening criteria for health promotion/disease prevention
      have become widely available in recent years, but their effect on day-to-day
      practice has been somewhat limited, highlighting the importance of emphasizing
      health promotion in family practice residency training. METHODS: To determine the
      extent and content of health promotion education in residency curricula and
      perceived shortcomings in this area, we conducted a survey of all 386 accredited
      family practice residency programs in the United States and Puerto Rico in
      February and April 1991, with a response rate of 80%. Program directors completed
      a two-page questionnaire on curriculum coverage of health promotion, subject
      areas included, and resources used. RESULTS: The survey found that 88% of
      residencies had a formal health promotion curriculum, with the most common topics
      being immunization protocols and hyperlipidemia and the least common topics being
      behavior change and compliance. American Academy of Family Physicians materials
      are the most common resources available in residencies, but the most frequently
      used is the US Preventive Services Task Force Report. Use of the latter resource
      varies by geographic location. CONCLUSION: Our study demonstrates that health
      promotion education is part of virtually all family practice residency training
      programs but also shows that use of available resources varies and that program
      directors find it difficult to help residents incorporate health promotion into
      day-to-day medical practice.

PMID- 1397830
TI  - Toward a good death: an interpretive investigation of family practice residents'
      practices with dying patients.
AB  - BACKGROUND: Physicians' encounters with dying patients are often problematic.
      This study was designed to facilitate understanding of what happens when
      residents encounter dying patients. METHODS: The research involved observing and
      interviewing 28 family practice residents as they worked with dying patients. The
      primary research technique was that of a grounded interpretive investigation.
      RESULTS: We found that working toward a "good death" was a central theme of the
      residents' everyday actions. At critical points, however, two important forces
      steered residents away from this central theme: biomedical technology and
      anxiety. Residents reacted to these forces by distancing, moving back toward a
      good death, or moving further from a good death. CONCLUSION: Understanding the
      oscillating course toward a good death will help residents, medical educators,
      and other physicians deal with dying patients and their families in more
      meaningful and satisfying ways.

PMID- 1397831
TI  - Voices from family medicine: Thomas Leaman. Interview by William B. Ventres and
      John J. Frey.
AB  - Thomas Leaman's relationship with the community of Hershey, Pa., extends over a
      period of 42 years. He began his commitment to that small central Pennsylvania
      community as one of its doctors; later he served as the first chair of the
      Department of Community and Family Medicine at the Pennsylvania State University
      School of Medicine in Hershey. He chaired the department from 1967 to 1987 and
      has been professor emeritus since that time. Dr. Leaman was president of the
      Society of Teachers of Family Medicine in 1982 and has continued to have an
      active role in many aspects of the Society, including the Long Range Planning and
      Medical Records Committees. He also served as a founding member of the
      Association of Departments of Family Medicine. This article is edited from
      interviews that occurred in May 1991 and July 1992.

PMID- 1397832
TI  - Biomedical research funding: view of the National Caucus of Basic Biomedical
      Science Chairs.

PMID- 1397833
TI  - Biophysics of the nineties: on the road to Budapest.

PMID- 1397834
TI  - Creating our children's NIH and other strategic challenges.

PMID- 1397835
TI  - Basic research: the lifeline of medicine.

PMID- 1397836
TI  - Gene expression: nutrient control of pre- and posttranscriptional events.
AB  - Regulation of gene expression by specific nutrients has become a major frontier
      for the next generation of nutrition scientists. The techniques of molecular
      biology allow us to define nutrient needs, as well as the outcomes of nutrient
      excesses, in terms of events that govern gene transcription, mRNA processing,
      mRNA stability, and mRNA translation. Evidence is presented showing that dietary
      constituents specifically modulate the nuclear events governing gene
      transcription and transcript processing. For example, fatty acid synthase gene
      transcription is inhibited by specific polyunsaturated fatty acids; S14 and
      pyruvate kinase genes contain a specific carbohydrate response element; and
      editing of apo B-100 to apo B-48 is enhanced by dietary carbohydrate. Nutrients
      such as iron and glucose are shown to control mRNA stability and translational
      rates of certain transcripts by regulating the interaction of cytosolic proteins
      with specific nucleotide sequences. The data of this review clearly demonstrate
      that nutrients play an active and specific role in governing the expression of
      select genes.

PMID- 1397837
TI  - Aerobic fermentation of glucose by trypanosomatids.
AB  - The consumption of glucose by trypanosomatid protozoa such as Trypanosoma brucei,
      Trypanosoma cruzi, Leishmania spp., and Crithidia spp. is characterized by the
      excretion of reduced products such as succinate, pyruvate, ethanol, L-alanine, or
      lactate (depending on the species) not only in anaerobiosis, but also under
      aerobic conditions. The "aerobic fermentation" of glucose is accompanied by a
      complete lack, or even a reversal, of the Pasteur effect. This peculiar
      catabolism is mediated by a so-far unique compartmentation of the glycolytic
      enzymes, most of which are placed in an organelle called the glycosome; by an
      almost complete lack of inhibitory controls at the level of hexokinase and
      phosphofructokinase; and by a central role of CO2 fixation through the reaction
      catalyzed by phosphoenolpyruvate carboxykinase. The production of fermentative
      products seems to be due to a relative inefficiency of the respiratory chain,
      which lacks NADH dehydrogenase and the first phosphorylation site and
      preferentially uses succinate as substrate.

PMID- 1397838
TI  - p53: the ultimate tumor suppressor gene?
AB  - Alterations in the gene encoding the cellular p53 protein are perhaps the most
      frequent type of genetic lesions in human cancer. At the heart of these
      alterations is the abrogation of the tumor suppressor activity of the normal p53.
      In many cases this is achieved through point mutations in p53, which often result
      in pronounced conformational changes. Such mutant polypeptides, which tend to
      accumulate to high levels in cancer cells, are believed to exert a dominant
      negative effect over coexpressed normal p53. Extensive research on p53,
      especially in the course of the last 3 years, has already provided much insight
      into the biological and biochemical mechanisms that underlie its capacity to act
      as a potent tumor suppressor. There are now many indications that p53 may play a
      central role in the control of cell proliferation, cell survival, and
      differentiation. Nevertheless, despite the purported importance of p53 for such
      crucial processes, mice can develop apparently without any defect in the total
      absence of p53. This raises the possibility that p53 may become critically
      limiting only when normal growth control is lost.

PMID- 1397839
TI  - Electromagnetic field effects on cells of the immune system: the role of calcium
      signaling.
AB  - During the past decade considerable evidence has accumulated demonstrating that
      nonthermal exposures of cells of the immune system to extremely low-frequency
      (ELF) electromagnetic fields (< 300 Hz) can elicit cellular changes that might be
      relevant to in vivo immune activity. A similar responsiveness to nonionizing
      electromagnetic energy in this frequency range has also been documented for
      tissues of the neuroendocrine and musculoskeletal system. However, knowledge
      about the underlying biological mechanisms by which such fields can induce
      cellular changes is still very limited. It is generally believed that the cell
      membrane and Ca(2+)-regulated activity is involved in bioactive ELF field
      coupling to living systems. This article begins with a short review of the
      current state of knowledge concerning the effects of nonthermal levels of ELF
      electromagnetic fields on the biochemistry and activity of immune cells and then
      closely examines new results that suggest a role for Ca2+ in the induction of
      these cellular field effects. Based on these findings it is proposed that
      membrane-mediated Ca2+ signaling processes are involved in the mediation of field
      effects on the immune system.

PMID- 1397840
TI  - mRNA degradation in procaryotes.
AB  - The fast turnover of mRNA permits rapid changes in the pattern of gene
      expression. In procaryotes, many enzymes involved in mRNA degradation have been
      identified and some of these endo- and exo-ribonucleases are now being
      intensively studied. Some of the structural features of mRNA that influence decay
      rates have also recently been defined. Although important components of the decay
      pathway are still elusive, a coherent and simple model for mRNA decay has emerged
      in the last few years.

PMID- 1397841
TI  - Biochemistry of carbohydrate-protein interaction.
AB  - Recognition of glycoconjugates is an important event in biological systems, and
      is frequently in the form of carbohydrate-protein interactions. To thoroughly
      understand these interactions, well-defined carbohydrate ligands must be
      available. Naturally derived glycoconjugates can be highly purified, and their
      structures (including conformational structures) can be elucidated to provide
      such ligands. This requires highly effective methods of separation, such as
      various forms of high-performance liquid chromatography. Alternatively,
      structurally well-defined glycoconjugates can be synthesized for this purpose.
      These include conjugates of carbohydrate derivatives to proteins, lipids, and
      nonbiological carriers and polymers. The efficacy of these conjugates is amply
      demonstrated in the studies of carbohydrate-binding proteins from animals.
      Hepatic carbohydrate receptors, requiring calcium for binding, recognize only the
      terminal sugar residues. Although different sugar specificities are manifested by
      different species, there is some commonality in the requirement of the
      substituents of the sugar rings. Clustering of the target sugars in proper
      geometric arrangement greatly enhances the binding by these proteins. Some other
      animal carbohydrate-binding proteins, however, may require penultimate sugars for
      optimal binding.

PMID- 1397842
TI  - Mechanisms of lead neurotoxicity, or looking beyond the lamppost.
AB  - Despite several decades of research on the neurotoxicology of lead and its
      continued prominence as a major environmental and occupational health hazard, the
      mechanisms of its toxic action in the nervous system are still unknown. The
      differential effects of lead exposure in young children and adults, as well as
      inconsistencies between in vivo and in vitro studies, suggest that lead toxicity
      may have multiple mechanisms in the central nervous system (CNS). Two are:
      neurodevelopmental toxicity, possibly involving interference with cell adhesion
      molecules, resulting in miswiring of the CNS during early development and
      possibly permanent dysfunction; and neuropharmacological toxicity, which might
      involve interactions between lead and calcium and lead and zinc, resulting in
      interference with neurotransmission at the synapse. This may be reversible.

PMID- 1397843
TI  - Membrane immunoglobulin and its accomplices: new lessons from an old receptor.
AB  - B lymphocytes express multisubunit receptors for antigen that play multiple roles
      in generation of the immune response. These receptors act as transmembrane signal
      transducers but also act to capture, concentrate, and internalize antigen for
      subsequent proteolytic processing and presentation to T cells. During the past
      decade great progress has been made in our understanding of the extended
      structure of the receptor and the molecular basis by which it transduces signals.
      It is now clear that the B cell antigen receptor is a complex structure composed
      of antigen binding and transducer/transporter substructures. The antigen binding
      substructure is composed of disulfide-linked immunoglobulin H and L chains, and
      is noncovalently associated with transducer/transporter substructures composed of
      disulfide-linked heterodimers of alpha, beta, and gamma chain products of the mb
      1 (alpha) and B29 (beta and gamma) genes. The cytoplasmic tails of these chains
      associate with src-family tyrosine kinases including fyn, lyn, blk, and lck and
      other SH2-containing molecules such as phosphatidylinositol 3-kinase. Available
      evidence indicates that these interactions are mediated via an amino acid
      sequence motif of approximately 22 amino acids that is found in both alpha and
      beta chains. Receptor ligation triggers the activation of multiple receptor
      associated src-family kinases leading to phosphorylation and activation of PLC
      gamma 1 and PLC gamma 2. Subsequent phosphoinositide hydrolysis and calcium
      mobilization, presumably acting in concert with other tyrosine kinase-activated
      mechanisms, leads to transcriptional activation of a number of immediate early
      genes and, ultimately, to B cell proliferation.

PMID- 1397844
TI  - On the initiation of glycogen and starch synthesis.

PMID- 1397845
TI  - [Cytochrome P-450IIIA, cyclosporine and drug interactions].

PMID- 1397846
TI  - [The estrogen-androgen profile is unchanged in men with cholelithiasis].
AB  - It is well established that cholelithiasis is more frequent in women than in men.
      This difference is usually explained by the effects of estrogens and progesterone
      on the metabolism of bile acids, biliary cholesterol secretion and saturation,
      and gallbladder motility. Another explanation could be a protective effect of
      androgens against cholelithiasis in men. To test this hypothesis, we determined
      the hormonal, androgenic and estrogenic, status of 15 male patients with
      asymptomatic gallstone disease and in 15 control patients with normal gallbladder
      matched for age and body weight. No significant difference in the plasma
      concentrations and the urinary excretion rate of sex hormones (testosterone,
      dihydrotestosterone, androstenedione, testosterone and androstanediol
      glucuronides, estradiol, estrone, total estrogens), as well as in the plasma sex
      hormone binding globulin, was found between the 2 groups of patients. The
      development of cholelithiasis in men, therefore, does not appear to be related to
      modification of sex steroids.

PMID- 1397847
TI  - [Celioscopic cholecystectomy. A survey of the French Society of Endoscopic
      Surgery and Operative Radiology. Apropos of 937 cases].
AB  - Twenty-eight surgeons, members of the Societe Francaise de Chirurgie Endoscopique
      et de Radiologie Operatoire, took part in this multicenter study, carried out
      between March 1989 and January 1991. Nine hundred and thirty-seven patients were
      entered into the study, 934 of whom presented with biliary lithiasis and 3 with
      gallbladder polyps. Biliary colic was found in 918 (98 percent) of patients. One
      hundred and twenty-five patients (13.3 percent) presented with acute
      cholecystitis. Laparoscopic cholecystectomy had to be converted to traditional
      laparotomy in 50 cases (5.3 percent). The most frequent causes of conversion were
      the presence of cholecystitis (34 percent) and the occurrence of hemorrhage which
      could not be controlled laparoscopically (18 percent). There was one death
      (mortality rate: 0.1 percent) and there were 37 postoperative complications
      (morbidity rate: 3.9 percent) which required reoperation in 11 instances: 4
      laparatomies, 5 laparoscopies and 2 ultrasonography guided drainages. The mean
      duration of postoperative hospital stay for patients without complications or
      conversion was 3.8 days. These results show both the limits and the advantages of
      laparoscopic cholecystectomy. This new technique is now well established and
      should be added to other therapies used in the treatment of patients with biliary
      lithiasis.

PMID- 1397849
TI  - [Pharmacokinetics and hepatic effects of cyclosporine A].

PMID- 1397848
TI  - [Effect of the severity of liver disease on renal hemodynamics and renal oxygen
      consumption in patients with cirrhosis].
AB  - In patients with cirrhosis, it has been shown that abnormal systemic and
      splanchnic hemodynamics and systemic oxygen (O2) consumption are related to the
      severity of liver disease. Little is known on the relationship between the
      severity of cirrhosis, on one hand, and renal hemodynamics and O2 consumption, on
      the other. We measured renal hemodynamics and renal O2 consumption in 31 patients
      Pugh's grade A and B and in 13 patients grade C. Systemic and splanchnic
      hemodynamics as well as systemic O2 consumption were studied. Renal blood flow,
      glomerular filtration rate, and renal O2 consumption were not significantly
      different between grades A and B and grade C patients. The renal fraction of
      systemic O2 consumption was higher (11.4 +/- 5.9 vs 7.9 +/- 4.1 percent
      respectively; P less than 0.05) and the systemic O2 consumption (111 +/- 23 vs
      128 +/- 26 ml.min-1.m-2 respectively; P less than 0.05) lower in patients with
      grade C than in grades A and B patients. The degree of systemic hyperkineticism
      and portal hypertension was related to the severity of cirrhosis. In our
      patients, renal hemodynamics and renal O2 consumption were not related to the
      severity of cirrhosis. However, liver failure was associated with an increased
      renal fraction of systemic O2 consumption due to unchanged renal O2 consumption
      and decreased systemic O2 consumption.

PMID- 1397850
TI  - [Anal incontinence: a new field of clinical and epidemiological research to
      invest].

PMID- 1397851
TI  - [Surgery of the esophagus under thoracoscopy. Study of feasibility].
AB  - An experimental study of thoracoscopic surgery on the esophagus was conducted in
      11 animals. Complete dissection of the esophagus was carried out in the ten last
      cases. Other procedures performed included mode picking, truncal vagotomies, and
      myotomies. The thoracoscopic esophageal surgery might allow to decrease the
      morbidity of thoracotomy. Its interest, compared with other methods of dissection
      without thoracotomy, has to be evaluated.

PMID- 1397852
TI  - A prospective study on duodenogastric reflux and on histological changes in
      gastric mucosa after cholecystectomy.
AB  - The authors carried out a prospective study to evaluate variations with time in
      postcholecystectomy duodenogastric reflux (expressed as "fasting bile reflux" in
      mumol/h) and in gastric mucosal damage. Ten patients underwent (before
      cholecystectomy, 6 months after surgery and after a median period of 4 years from
      surgery) a gastric drainage to assess total (enzymatic method) and single (high
      performance liquid chromatography) intragastric bile acids, and a gastroscopy
      with biopsies of the antrum and gastric body to assess histological damage to the
      mucosa. The results showed that there was a progressive increase in the fasting
      bile reflux of total bile acids with time (precholecystectomy median value 0.295
      mumol/h; 6 months control median value 12.045 mumol/h; late control medial value
      19.9 mumol/h; Friedman test, P = 0.0022). Examination of the gastric mucosa at
      the three moments of the study showed that histological damage worsened
      progressively. In fact chronic atrophic gastritis of the antrum was present in 10
      percent of cases before surgery and in 50 percent 4 years after, and the
      prevalence of chronic superficial gastritis of the body progressed from 0 to 40
      percent. Studies on larger groups of patients are necessary to evaluate whether
      these two phenomena are correlated.

PMID- 1397853
TI  - Effects of alverine on the spontaneous electrical activity and nervous control of
      the proximal colon of the rabbit.
AB  - To analyse the mechanisms of the antispasmodic action of alverine, the effects of
      this drug on the spontaneous motility and nervous control of the proximal colon
      of the rabbit were studied in vivo. The electrical activity of the colonic smooth
      muscle was recorded using extracellular electrodes. The parasympathetic efferents
      were activated by electrical stimulation of distal ends of the vagus nerves.
      Alverine given intravenously inhibits spike potentials without modifying the slow
      waves. Excitatory and inhibitory responses induced by parasympathetic efferent
      stimulations, as well as the hyperpolarization due to intraluminal distension,
      were also blocked after drug injection. Our results show that alverine is able to
      block the spontaneous contractions and the nervous control of rabbit proximal
      colon, indicating that this drug has powerful antispasmodic effects.

PMID- 1397854
TI  - [Assessment of the practice of adjuvant radiotherapy in cancer of the rectum in
      the department of Calvados].
AB  - The effectiveness of adjuvant radiotherapy (ART) in the treatment of rectal
      cancer (RC) is established for the local control of the tumor, but doubt remains
      as concerns improvement in survival. The aim of this work was to assess the
      present techniques and trends of ART in a French department based on a population
      based study. From 1978 to 1986, 616 cases of RC were diagnosed in the department
      of Calvados (France). Tumor was removed in 346 patients (56 percent). Of these
      346 cases, 29 percent were irradiated, 3/4 postoperatively and one forth
      preoperatively. Besides sex and age, the type of surgery (anal sphincter saving
      or not) and Dukes' tumor stade had an influence on the performance of ART. Thirty
      one percent Dukes B tumors and 42.1 percent of Dukes C tumors were irradiated.
      The practice of ART for these tumors increased significantly from 1978 (18.5
      percent) to 1986 (60 percent) (P less than 10(-4)). However, the practice and the
      distribution of centers performing ART were heterogenous within the department of
      Calvados. This heterogeneity was neither due to the environment (urban/rural) of
      the patient nor to the distance between the place of residence and the radiation
      therapy center. Such an heterogeneity could be explained only by the lack of
      consensus concerning the practice of ART. Such a consensus could be found
      considering the results of the latest controlled clinical trials, but definitive
      conclusions are needed about the effectiveness of ART on the improvement of
      survival.

PMID- 1397855
TI  - [Prevalence of anal incontinence in adults].
AB  - Inquiries were conducted to determine the prevalence of anal incontinence in a)
      the general population over 45 by a gallup poll studying 1,100 persons (A); b)
      3,914 patients seen by their general practitioner or their gastroenterologist
      during the same week (B); c) 500 patients consulting for urinary stress
      incontinence (C1); d) 1,136 neurological patients suffering from micturation
      disorders (C2); and e) 10,157 elderly persons living in retirement homes or in
      hospital (D). In the general community (A), the prevalence of anal incontinence,
      including gas and stool incontinence, was 11 percent, the prevalence of fecal
      incontinence, 6 percent, the prevalence of daily or weekly fecal incontinence, 2
      percent; prevalences were respectively 15.5 percent, 7.9 percent, and 3.2 percent
      in group B, and 27 percent, 9 percent and 3.8 percent in group C1. The prevalence
      of fecal incontinence was 18 percent in group C2 and 33 percent in group D.
      Prevalence did not depend on age in group A and C1, but was twofold higher in
      group C1 than in group A. The prevalence increased with age in groups B and D.

PMID- 1397856
TI  - [Severe hepatitis with encephalopathy induced by acetylsalicylic acid in a case
      of lupus erythematosus disseminatus].
AB  - The observation of a 62 year-old woman who had been suffering from arthritis for
      several years and in whom treatment with high doses of acetylsalicylic acid
      resulted in severe acute hepatitis is reported. Clinical and serological findings
      led to the diagnosis of systemic lupus erythematosus complicated by acute drug
      induced hepatitis.

PMID- 1397857
TI  - [Rupture of the distal thoracic esophagus by closed trauma].
AB  - Closed traumatic rupture of the esophagus is uncommon, usually located in the
      upper third of the esophagus. We report a case occurring in the lower third. This
      diagnosis must be envisaged when faced with delayed clinical and radiological
      signs. The prognosis is severe and the therapeutic decisions are controversial.

PMID- 1397858
TI  - [Primary malignant melanoma of the small intestine].
AB  - The small intestine is a frequent site for metastases of cutaneous or ocular
      melanoma. When the latter are absent, the diagnosis of primary intestinal
      melanoma can be proposed. Primary malignant melanoma of the small intestine
      arises from melanoblastic cells of the neural crests, which migrate to the distal
      ileum through the omphalomesenteric canal. Incomplete regression of the later
      leads to persistence of Meckel's diverticulum. We report herein a case of
      malignant melanoma of the small intestine without evidence of a cutaneous and/or
      ocular origin. Based on its location in the distal ileum, we propose that this
      tumor be classified as a primary malignant melanoma of the small intestine.

PMID- 1397859
TI  - [Immediate acute hepatic cytolysis after the administration of a single amineptin
      tablet].

PMID- 1397860
TI  - [Cytolytic hepatitis induced by cisapride].

PMID- 1397861
TI  - Anti-HCV RIBA II test in non-A, non-B chronic active hepatitis.

PMID- 1397862
TI  - [Partially reversible secondary achalasia after thoracic radiation. Value of
      nifedipine].

PMID- 1397863
TI  - [Is graded esophageal balloon distension harmless?].

PMID- 1397864
TI  - [Treatment of pseudocyst in chronic pancreatitis by puncture-drainage and
      octreotide combination].

PMID- 1397866
TI  - [Primary acute panniculitis: value of celioscopy].

PMID- 1397865
TI  - [Cirkan-induced chronic diarrhea].

PMID- 1397867
TI  - [Rectal lymphoma: endorectal ultrasound aspect].

PMID- 1397868
TI  - [Postoperative gastroparesis after partial gastrectomy for ulcer: should total
      gastrectomy be preferred?].

PMID- 1397869
TI  - AGA governing board policy statement on training and education.

PMID- 1397870
TI  - Human gastric and jejunal transit and motility after Roux gastrojejunostomy.
AB  - Upper gut transit and motility among 10 symptomatic and 9 asymptomatic patients
      with Roux gastrectomy were compared with those among 10 healthy, unoperated
      controls. Gastric emptying of solids and Roux limb and small intestinal transit
      of liquids were assessed scintigraphically. Motor patterns in the Roux limb or
      healthy jejunum were recorded manometrically. Whereas gastric emptying was
      sometimes faster and sometimes unchanged after Roux gastrectomy compared with
      controls, Roux limb transit in patients was consistently slower than jejunal
      transit in controls. Postprandially, the Roux limb showed decreased overall
      motility, fewer clustered waves, and less aboral migration of clustered waves
      than the healthy jejunum. Symptomatic Roux patients had jejunal transit and motor
      patterns similar to those of asymptomatic patients. Nonetheless, reflux from Roux
      limb to gastric remnant occurred in 4 of 10 symptomatic patients but in none of
      the asymptomatic patients. In conclusion, stasis and dysmotility are present in
      the Roux limb after Roux gastrectomy and Roux-gastric reflux can occur. Other
      factors, however, must have a role in determining whether symptoms appear.

PMID- 1397871
TI  - Short-chain fatty acids in pouch contents from patients with and without
      pouchitis after ileal pouch-anal anastomosis.
AB  - Fecal concentrations of short-chain fatty acids were markedly reduced in 6
      patients with pouchitis (mean +/- SE, 56.2 +/- 13.3 mmol/L) compared with 28
      patients without pouchitis (139.0 +/- 8.5 mmol/L; P less than 10(-3)). The ratios
      of acetate to propionate to butyrate were not changed (pouchitis, 75:12:11%;
      normal pouches, 76:12:11%), i.e., all acids were equally reduced. The 24-hour
      production of total short-chain fatty acids in 16.6% fecal homogenates from
      patients with pouchitis was decreased (17.5 +/- 5.3 mmol/L) compared with
      patients without pouchitis (33.3 +/- 3.4 mmol/L; P less than 0.05), which could
      be overcome by the addition of saccharides to the homogenates. Pouch excretions
      of saccharides were similar in the two groups, but dilution occurred during
      pouchitis because of the increased outputs. Concentrations and productions of
      short-chain fatty acids correlated with pouch concentrations and excretions of
      sodium and saccharides. L-Lactate was elevated in pouchitis outputs, but
      differences in stool culture counts, mucosal histology, fecal concentration,
      assimilation or production of ammonia, nitrogen excretion, pH, and osmolality
      were not found. Pouchitis is characterized by decreased fecal concentrations and
      productions of short-chain fatty acids possibly caused by low pouch
      concentrations of fermentable saccharides.

PMID- 1397872
TI  - Lactase gene expression during early development of rat small intestine.
AB  - Expression of lactase messenger (m) RNA and protein in rat small intestine during
      fetal and postnatal development was analyzed using in situ hybridization and
      immunohistochemistry. Lactase mRNA was first identified at 18 days of
      development, and lactase protein was first detected at day 20. Lactase mRNA and
      protein were present along the entire villus. Lactase mRNA increased, reaching a
      maximum at day 20. Just before birth a decrease in lactase mRNA was observed. In
      newborn intestine, lactase mRNA was present only from the base of the villus up
      to the mid-villus region and was undetectable up to the villus tips. Lactase
      protein continued to be expressed along the entire villus. These data show that
      expression of lactase mRNA and protein do not parallel, indicating a
      posttranscriptional control in fetal development. Lactase gene transcription is
      initiated late in gestation concomitant with villus formation and is exclusively
      seen in villus epithelial cells. The restriction after birth of lactase mRNA
      expression to cells at the villus base suggests the occurrence of a previously
      unknown step in postnatal differentiation of the enterocyte.

PMID- 1397873
TI  - Boosted mucosal immune responsiveness in the rat intestine by actively
      transported hexose.
AB  - Anaphylaxis-mediated intestinal fluid secretion was measured in Trichinella
      spiralis- or ovalbumin-immunized rats challenged intraduodenally with T. spiralis
      somatic antigen (1 mg protein/0.5 mL saline) or ovalbumin (1 mg/0.5 mL saline),
      respectively. Intestinal fluid volume was measured 30 minutes after challenge as
      an index of net secretion. Challenge with the antigenic bolus containing 40
      mmol/L D-glucose induced twice the fluid secretion as that induced by either
      antigen alone. L-Glucose was an ineffective substitute for D-glucose. The
      enhancement of secretion by D-glucose was dependent on prior immunologic
      sensitization, was diminished in the presence of phlorizin, and was mimicked by
      beta-methyl glucoside. Results indicate that the active transport of D-glucose
      augments the antigen-mediated fluid secretion, possibly by enhancing permeation
      of the intestinal epithelium to antigen, thereby providing greater access to the
      mucosal immune system.

PMID- 1397874
TI  - Scintigraphic demonstration of lactulose-induced accelerated proximal colon
      transit.
AB  - Although lactulose, a widely used cathartic, is known to increase stool
      frequency, details of its site of action in the colon are obscure. In the present
      study a noninvasive scintigraphic technique was used to closely follow the
      movements of proximal colonic contents. Lactulose, 10-20 mL three times daily,
      significantly accelerated mean transit through the ascending colon from 12.9 +/-
      3.7 to 7.0 +/- 2.5 hours (n = 11; P less than 0.01). This was associated with the
      occurrence of mass movements, with six such events seen during lactulose
      treatment whereas only one was seen during the control study (P less than 0.05).
      Lactulose also accelerated movement through the rest of the colon so that at 24
      hours after dosing the geometric center of the isotope bolus was distal to that
      seen during the control study (6.6 +/- 1.2 vs. 4.7 +/- 1.3; n = 11, P less than
      0.001). This model of diarrhea in otherwise normal subjects was subsequently used
      to study the effects of viscous gels in diarrhea. The viscous and relatively
      poorly fermented gel ispaghula, 3.5 g three times daily, abolished mass movements
      and was associated with a small but significant increase in proximal colonic
      transit time, which increased from 6.1 +/- 2.1 to 7.7 +/- 1.5 hours (n = 8; P
      less than 0.05). By contrast, the viscous but readily fermentable gelling agent
      guar gum, 5 g three times daily, further accelerated the cathartic effect of
      lactulose, with the mean transit time decreasing from 6.4 +/- 2.3 to 4.7 +/- 1.7
      hours (n = 8; P less than 0.05). The acceleration of proximal colonic transit by
      lactulose may be a useful model to study diarrhea and its modification by
      therapy.

PMID- 1397875
TI  - In vivo bicarbonate secretion by human esophagus.
AB  - The capacity of the human esophagus to secrete bicarbonate was studied in vivo in
      10 healthy subjects. A 10-cm segment of the lower esophagus was isolated between
      two balloons, and the segment was perfused with an unbuffered isotonic saline
      solution (pH 7) for 30 minutes. The perfusate was collected, pooled, and analyzed
      for bicarbonate using a sensitive back-titration method. Measurements of aspirate
      amylase and salivary amylase and bicarbonate permitted correction of perfusate
      bicarbonate values for contamination by swallowed saliva. The esophagus of all 10
      subjects were found to secrete bicarbonate in amounts ranging from 10 to 274
      microEq/30 min (average, 78 microEq/30 min); based on in vitro studies, these
      amounts of bicarbonate were shown to be capable of neutralizing enough residual
      acid from an episode of reflux to increase pH from 2.5 almost to neutrality (pH 6
      7). These findings document the presence within the human esophagus of an
      additional mechanism for defense against (acid) reflux damage, namely, through
      enhanced luminal acid clearance by the secretion of bicarbonate ions.

PMID- 1397876
TI  - Effects of chronic superficial injury on the rat gastric mucosa.
AB  - The effects of chronic superficial injury on the stomach were studied in rats
      dosed with a mild irritant (2 mol/L NaCl intragastrically) every 48 hours for 1
      month followed by 1-month recovery. A single exposure to this mild irritant
      induced gross protection against 6 mol/L NaCl for 1 but not 2 days. Leukotriene
      C4 (LTC4) levels increased slightly. Prostaglandin E2 (PGE2) concentration was
      unchanged. After 2-week dosing, protection was concomitant with markedly elevated
      PGE2 concentration. LTC4 values remained unchanged. Superficial epithelial cells
      were more resistant to damage. After 4-week dosing, protection occurred at 1 but
      not 2 days after the dose with an inverse correlation of PGE2. LTC4 concentration
      increased significantly at both times. Chronic injury for 1 month did not alter
      rapid epithelial restitution or PGE2 and LTC4 released 15 minutes after challenge
      with 6 mol/L NaCl. The recovery period showed loss of protection. PGE2 values
      returned to control levels but LTC4 values remained slightly elevated. It is
      concluded that short- or long-term (4-week) "adaptive cytoprotection" is not
      mediated by endogenous PGE2. Only extremely high levels of LTC4 correlated with
      loss of protection. The role of the more resistant superficial epithelium remains
      unknown.

PMID- 1397877
TI  - Monthly variation of hospital admission and mortality of peptic ulcer disease: a
      reappraisal of ulcer periodicity.
AB  - The occurrence of peptic ulcer is characterized by a seasonal variation, the
      meaning of which is poorly understood. The present study examined the periodicity
      of hospital admissions and mortality resulting from gastric and duodenal ulcer to
      determine its etiologic relevance. Ulcer periodicity was studied in the
      nationwide data sets of the Department of Veterans Affairs, the Health Care
      Financing Administration, and the Vital Statistics. Both ulcer types were
      characterized by similar patterns of periodicity. Hospital admissions peaked
      during the first 3 months of the year, followed by a marked decline during summer
      and a second smaller peak around October. This pattern occurred independently of
      age, sex, race, and place of residence. It also pertained to ulcers complicated
      by hemorrhage or perforation. Although total admissions peaked earlier during the
      year and showed a less consistent peak in October, there was a close resemblance
      between the periodicity of all diseases and that of peptic ulcer. Mortality was
      highest in January and lowest in July for all disease and ulcer diseases alike.
      The similarity between the periodicity of peptic ulcer and other diseases
      suggests that the major factors responsible for the cyclic behavior of gastric
      and duodenal ulcer are not particular to these diseases but affect other
      unrelated diseases alike.

PMID- 1397878
TI  - Effect of loxiglumide on basal and gastrin- and bombesin-stimulated gastric acid
      and serum gastrin levels.
AB  - The effect of the specific cholecystokinin-receptor antagonist loxiglumide on
      basal and bombesin-, and gastrin 17-I-stimulated gastric acid secretion and serum
      gastrin levels was studied in 12 healthy subjects. Loxiglumide (10 mg.kg-1.h-1)
      significantly augmented basal gastric acid output from 1.8 +/- 0.3 to 3.9 +/- 0.6
      mmol H+/h (P less than 0.005) but did not significantly influence integrated
      basal serum gastrin concentrations (2 +/- 21 vs. 32 +/- 21 pmol L-1.h-1). Both
      gastric acid secretion and integrated serum gastrin concentrations stimulated by
      bombesin infusion (92.6 pmol.kg-1.h-1) were significantly augmented by
      loxiglumide [from 4.0 +/- 0.3 to 10.0 +/- 1.3 mmol H+/h (P less than 0.005) and
      from 1251 +/- 93 to 2558 +/- 206 pmol.L-1.h-1 (P less than 0.005), respectively].
      Gastric acid output and serum gastrin concentrations during infusion of 5 pmol.kg
      1.h-1 of synthetic human gastrin 17-I (9.6 +/- 2.9 mmol H+/h and 1045 +/- 177
      pmol.L-1.h-1) and during infusion of 15 pmol.kg-1.h-1 of gastrin 17-I (14.5 +/-
      3.1 mmol H+/h and 2412 +/- 312 pmol.L-1.h-1) were not significantly influenced by
      loxiglumide (10.3 +/- 2.3 mmol H+/h and 1291 +/- 257 pmol.L-1.h-1 for the 5
      pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide and 13.6 +/- 3.4 mmol
      H+/h and 2611 +/- 305 pmol.L-1.h-1 for the 15-pmol.kg-1.h-1 gastrin 17-I infusion
      dose with loxiglumide). These data indicate that endogenous cholecystokinin
      inhibits gastric acid secretion under basal conditions and gastrin release and
      gastric acid secretion during infusion of bombesin in humans and suggest that the
      augmented effect of loxiglumide on bombesin-stimulated gastric acid secretion may
      be explained largely by enhanced gastrin release.

PMID- 1397879
TI  - Pharyngeal (Zenker's) diverticulum is a disorder of upper esophageal sphincter
      opening.
AB  - Pharyngeal coordination, sphincter opening, and flow pressures during swallowing
      were investigated in patients with pharyngeal (Zenker's) diverticula. Fourteen
      patients with diverticula and 9 healthy age-matched controls were studied using
      simultaneous videoradiography and manometry. Pharyngeal and upper esophageal
      sphincter pressures were recorded by a perfused side hole/sleeve assembly.
      Temporal relationships among swallowing events, extent of sphincter opening
      during swallowing, and intrabolus pressure during bolus passage across the
      sphincter were measured. The timing among pharyngeal contraction and sphincter
      relaxation, opening, and closure did not differ between patients and controls.
      Sphincter opening was significantly reduced in patients compared with controls in
      sagittal (P = 0.0003) and transverse (P = 0.005) planes. Manometric sphincter
      relaxation was normal in patients. Intrabolus pressure was significantly greater
      in patients than in controls (P = 0.001). It is concluded that Zenker's
      diverticulum is a disorder of diminished upper esophageal sphincter opening that
      is not caused by pharyngosphincteric incoordination or failed sphincter
      relaxation. Incomplete sphincter opening is likely to cause dysphagia. Increased
      hypopharyngeal pressures during swallowing are probably important in the
      pathogenesis of the diverticulum.

PMID- 1397880
TI  - Effect of a catheter in the pharynx on the frequency of transient lower
      esophageal sphincter relaxations.
AB  - Transient relaxation of the lower esophageal sphincter (LES) is observed fairly
      frequently during prolonged continuous monitoring of the LES. The aim of this
      study was to test whether the presence of a catheter in the pharynx through the
      stimulation of mechanoreceptors may induce transient LES relaxation. LES and
      esophageal pressure recordings were obtained for 1 hour in six subjects with a
      manometric catheter placed via a gastrostomy tube. Swallowing was monitored by
      submental electromyographic recording. Additional recordings were obtained in
      these subjects with a catheter placed in the pharynx for 1 additional hour.
      Transient LES relaxations were recorded in both study periods, i.e., with and
      without a catheter in the pharynx. The frequency of transient LES relaxations was
      significantly higher in the presence of manometric catheters in the pharynx (6.4
      +/- 2.2 vs. 2.0 +/- 1.1 total LES relaxations). The frequency of transient LES
      relaxation during the first and second hour after placement of the manometric
      catheter in a group of seven healthy subjects was not significant different. It
      is concluded that the pharynx is one of the sites that may mediate the induction
      of transient LES relaxation.

PMID- 1397881
TI  - Barrett's esophagus: age, prevalence, and extent of columnar epithelium.
AB  - The development of Barrett's esophagus was studied using data from 51,311
      patients undergoing upper gastrointestinal endoscopy between 1976 and 1989. Three
      hundred seventy-seven patients had greater than or equal to 3-cm columnar
      epithelium in the esophagus and no carcinoma. The prevalence of Barrett's
      esophagus increased with age to reach a plateau by the seventh decade. Half of
      the maximum prevalence was reached by age 40 years, the estimated median age of
      development of the disorder. Unlike prevalence, the mean length of columnar
      epithelium did not increase with age. No significant change in length was found
      in 21 patients followed up for a mean of 7.3 years (mean initial length, 8.29 +/-
      0.85 cm; mean final length, 8.33 +/- 0.77 cm). The length of columnar epithelium
      did not increase in the presence of esophagitis or decrease when esophagitis was
      absent. Mean age at diagnosis of Barrett's esophagus was 63 years without
      carcinoma and 64 years in a separate group of patients with adenocarcinoma. The
      data are consistent with a fairly rapid evolution of Barrett's esophagus to its
      full length with little subsequent change. Barrett's esophagus may develop more
      than 20 years before the mean age of clinical recognition or the development of
      esophageal adenocarcinoma.

PMID- 1397882
TI  - Effect of neurotensin on gut mucosal growth in rats with jejunal and ileal Thiry
      Vella fistulas.
AB  - Neurotensin (NT) stimulates growth of normal and atrophic small bowel mucosa; the
      mechanisms for this trophic effect of NT are not completely known. The purpose of
      this study was to (a) determine whether the trophic effect of NT is mediated by
      mechanisms involving luminal or nonluminal factors and (b) determine whether NT
      exerts a differential trophic effect on either jejunal or ileal mucosa. Twenty
      eight male Sprague-Dawley rats underwent construction of either a jejunal or
      ileal Thiry-Vella fistula (TVF). After a 1-week recovery period, rats were
      further subdivided into groups to receive either saline (control) or NT (300
      micrograms/kg). Rats were killed on day 6, and TVF as well as corresponding
      segments of intact jejunum or ileum were removed. Mucosa was scraped, weighed,
      and analyzed for DNA and protein content. In addition, representative sections of
      full-thickness bowel from each group were examined histologically. In the jejunal
      TVF group, NT increased mucosal growth measurements in both the TVF and the
      intact jejunum. However, in the ileal TVF group, NT stimulated proliferation of
      intact ileal mucosa only; it had no effect on ileal mucosa in the TVF. These
      results suggest that NT exerts a systemic effect independent of luminal factors
      on the proliferation of proximal gut mucosa in addition to an indirect effect
      produced by stimulation of endogenous luminal secretions. In contrast, an
      indirect mechanism appears to be the predominant action of NT on growth of distal
      gut mucosa.

PMID- 1397883
TI  - Neutrophil-mediated nitrosamine formation: role of nitric oxide in rats.
AB  - It is well known that chronic inflammation of the colon and rectum is associated
      with an increased risk of colorectal cancer, but the mechanisms by which
      inflammation promotes neoplasia remain undefined. The authors propose that
      inflammatory neutrophils may produce carcinogenic nitrosamines via the L-arginine
      dependent formation of nitrogen oxides such as nitric oxide. Therefore, the
      objectives of the study were to characterize the L-arginine-dependent formation
      of nitrogen oxides by inflammatory (elicited) neutrophils using conditions that
      more closely mimic the extravascular (i.e., interstitial) compartment of the gut
      and to characterize the neutrophil-dependent N-nitrosation of a model amine to
      yield its nitrosamine derivative. In the absence of any metabolic activation,
      adherent, inflammatory neutrophils (2 x 10(6) cells) produced 12.8 +/- 1.4
      mumol/L of nitrite during a 4-hour incubation period. Omission of L-arginine
      and/or inhibition of nitric oxide synthase by the addition of 1 mmol/L NG-nitro-L
      arginine methyl ester (L-NAME) resulted in 35%-78% inhibition of nitrite
      production, suggesting that nitrite was derived from nitric oxide. By comparison,
      neither circulating rat neutrophils nor elicited rat macrophages produced
      significant amounts of nitrite under the same conditions. Furthermore, elicited
      neutrophils (2 x 10(6) cells) were capable of N-nitrosating 2,3
      diaminonaphthalene to yield its nitrosamine derivative 1-naphtho-2,3-triazole
      (282 +/- 12 nmol/L) in a time- and cell-dependent pattern similar to that of
      nitrite production. Addition of a variety of antioxidants (e.g., ascorbic acid,
      reduced glutathione, alpha-tocopherol analog), 5-aminosalicylic acid, or L-NAME
      resulted in 80%-85% inhibition of neutrophil-mediated nitrosamine formation.
      Taken together, these data suggest that inflammatory neutrophils may represent an
      important metabolic source of endogenous carcinogens during times of active
      intestinal inflammation.

PMID- 1397884
TI  - Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal
      hemorrhage.
AB  - To assess the efficacy of selective intestinal decontamination with norfloxacin
      in the prevention of bacterial infections in cirrhotic patients with
      gastrointestinal hemorrhage, 119 patients were included in a prospective
      randomized study. Group 1 (n = 60) received norfloxacin orally or through a
      nasogastric tube, 400 mg twice daily for 7 days beginning immediately after
      emergency gastroscopy; group 2 (n = 59) was the control group. We found a
      significantly lower incidence of infections (10% vs. 37.2%; P = 0.001),
      bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than
      0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving
      norfloxacin, as a consequence of decrease in the incidence of infections caused
      by aerobic gram-negative bacilli. The decrease in mortality observed in the
      treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost
      for antibiotic treatment showed a 62% reduction in the treated group compared
      with the control group. The results show that selective intestinal
      decontamination with norfloxacin is useful in preventing bacterial infections in
      cirrhotics with gastrointestinal hemorrhage.

PMID- 1397885
TI  - Bromobenzene accelerates hepatocyte streaming in rats.
AB  - Sixty male adult rats weighing between 250 and 300 g were divided in two equal
      experimental groups. The first experiment was designed to evaluate hepatocyte
      streaming. Animals were injected with 0.5 microCi [3H]thymidine and 1 hour later
      received one intraperitoneal injection of bromobenzene (3.8 mmol/kg, dissolved in
      corn oil). The animals were then killed in groups of five at 1 hour and 2, 4, 7,
      14, and 30 days. The aim of the second experiment was to evaluate labeling index
      changes with time. Animals received one intraperitoneal injection of bromobenzene
      and were killed in groups of five at 1, 2, 3, 4, 7, and 14 days. They received
      [3H]thymidine 1 hour before killing. Bromobenzene induced a necrosis in the third
      acinus zone that disappeared within a week. On day 0 the labeling index of
      hepatocytes and littoral cells was 0.3% +/- 0.04% and 0.4% +/- 0.05%,
      respectively. On the second day, it reached 14.6% +/- 2.6% and 10.1% +/- 3.1% and
      returned to its initial value after 1 week. Dead cells in the third zone were
      replaced by inflowing cells from the intact zones. Hepatocytes and littoral cells
      streamed at the same velocity of 6 +/- 0.5 micron/day, faster than in untreated
      animals with velocity of 3.2 microns/day. Parenchyma and stroma responded to
      injury in a coordinated fashion. From the functional point of view, hepatocytes
      and littoral cells operate as a unit that is called proliferon. The maximal
      proliferon life span was 57 days after bromobenzene treatment and 108 days in
      controls.

PMID- 1397886
TI  - Inhibition of nucleation and crystal growth of calcium carbonate by human
      lithostathine.
AB  - Pancreatic juice is naturally supersaturated in calcium and bicarbonate ions. A
      mechanism controlling CaCO3 crystal formation and growth is therefore necessary
      to prevent duct clogging. The present study shows that lithostathine, a
      glycoprotein present in human pancreatic juice at a concentration in the range of
      10 mumol/L, could be involved in such a control. Lithostathine in concentrations
      greater than 1.5 mumol/L significantly delayed crystal nucleation and inhibited
      growth of preformed CaCO3 crystals from supersaturated solutions. Adsorption of
      lithostathine on crystals was shown by immunodetection. Albumin also adsorbed on
      CaCO3 crystals, but neither albumin nor other pancreatic secretory proteins
      inhibited crystal nucleation or growth. Lithostathine adsorbed to sites
      specifically inhibiting crystal growth with a dissociation constant (Kd) = 0.9 x
      10(-6) mol/L. The glycosylated amino-terminal undecapeptide generated by limited
      trypsin hydrolysis inhibited CaCO3 crystal growth with a Kd = 3.0 x 10(-6) mol/L,
      similar to that of lithostathine. On the contrary, the carboxy-terminal
      polypeptide was inactive. A synthetic undecapeptide identical to the N-terminal
      end but not glycosylated was equally active. The activity disappeared upon
      digestion of the undecapeptide with V8 protease. The N-terminal undecapeptide of
      lithostathine is therefore essential to the inhibitory activity of the protein on
      CaCO3 crystal growth.

PMID- 1397887
TI  - Frequency and significance of antibodies to liver/kidney microsome type 1 in
      adults with chronic active hepatitis.
AB  - To assess the frequency of antibodies to liver/kidney microsome type 1 (anti
      LKM1) in patients with chronic active hepatitis, 131 such patients were tested by
      an indirect immunofluorescence assay. Of 62 patients with type 1 autoimmune
      hepatitis, none were seropositive. In contrast, 3 of 11 patients with autoimmune
      hepatitis and antimitochondrial antibodies (27%) were seropositive for anti-LKM1.
      Each had responded to corticosteroid therapy, and retesting of sera confirmed
      that each had been misclassified as antimitochondrial antibody positive. None of
      the patients with chronic active hepatitis B (14 patients) or C (24 patients) had
      anti-LKM1. Similarly, none of the 20 patients with cryptogenic disease had these
      antibodies. It is concluded that anti-LKM1 is specific for type 2 autoimmune
      hepatitis and is infrequent in adult patients seen at a referral center in the
      United States for chronic active hepatitis. Anti-LKM1 reactivity may be
      misinterpreted as antimitochondrial antibody reactivity by indirect
      immunofluorescence. Chronic hepatitis B and C virus infections are not important
      stimuli for the production of anti-LKM1, and testing for anti-LKM 1 is unlikely
      to clarify the nature of cryptogenic disease.

PMID- 1397888
TI  - Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a
      study of normal subjects and alcoholic cirrhotics.
AB  - Patients with alcoholic liver cirrhosis (ALC) have high serum levels and
      spontaneous in vitro production of immunoglobulin (Ig) A. Deposits of IgA are
      also found in liver sinusoids. Increased interleukin 6 (IL-6) production is
      another feature of this disease. This study shows a linear correlation between
      increased lipopolysaccharide (LPS)-induced IL-6 production and increased
      spontaneous IgA and IgG secretion by peripheral blood mononuclear cells (PBMCs).
      PBMCs and purified monocytes isolated from healthy control subjects and patients
      with ALC contain elevated IL-6 messenger RNA levels and produce IL-6 in response
      to stimulation with soluble polymeric IgA (p-IgA) or attached monomeric IgA (m
      IgA) but not with soluble m-IgA. The addition of monospecific antibody to human
      IL-6 inhibits spontaneous IgA production by PBMC. This inhibition is more
      pronounced in patients with ALC. These data provide evidence that IgA, possibly
      by attachment to cells possessing Fc alpha receptors and secreting IL-6, is
      involved in the production of this major mediator and the amplification of Ig
      secretion. Circulating IgA and IgA deposits could therefore initiate a process of
      autoamplification implicated in the development of hypergammaglobulinemia in ALC.

PMID- 1397889
TI  - Mobilization of malignant ascites with diuretics is dependent on ascitic fluid
      characteristics.
AB  - Serial ascites and plasma volumes were measured during diuresis in nine patients
      with ascites caused by peritoneal carcinomatosis, four patients with chylous
      malignant ascites, and three patients with portal hypertension-related ascites
      caused by massive hepatic metastases. Oral diuretics were given to achieve an
      adequate natriuresis on a sodium-restricted diet. During the study period (7.8 +/
      3.2 days), patients with peritoneal carcinomatosis and chylous ascites lost 0.49
      +/- 0.31 and 0.51 +/- 0.42 kg/day in weight, respectively, with negligible change
      in ascites volumes (-0.03 +/- 0.11 and 0.02 +/- 0.09 L/day). Patients with
      ascites caused by massive hepatic metastasis lost 1.06 +/- 0.15 kg/day in weight
      (P = 0.01 for massive hepatic metastasis vs. peritoneal carcinomatosis) and 0.23
      +/- 0.13 L/day of ascites (P less than 0.05 vs. other groups). Plasma volume
      changes were not significantly different among the three groups. Patients with
      edema (9/16) had a greater natriuresis and daily weight loss. Three patients with
      peritoneal carcinomatosis and one with chylous ascites developed renal
      dysfunction or symptomatic hypotension. No patient with massive hepatic
      metastasis developed these complications. In patients with ascites caused by
      peritoneal carcinomatosis or chylous malignant ascites there is no mobilization
      of ascites, whereas in patients with massive hepatic metastasis, ascites may be
      mobilized with diuretics.

PMID- 1397891
TI  - Synthesis of cellular fibronectin by rat liver fat-storing (Ito) cells:
      regulation by cytokines.
AB  - Fibronectins are multifunctional extracellular matrix glycoproteins that seem to
      play a pacemaker role in liver fibrogenesis. The expression of cellular
      fibronectin by rat liver fat-storing cells in primary culture and their
      modulation by cytokines was studied. Cellular fibronectin was localized in the
      cytoplasm and on the surface of cultured fat-storing cells as well as in
      extracellular matrix fibrils by indirect immunofluorescence. Immunoprecipitation
      of endogenously labeled fibronectin using type specific antibodies showed the
      synthesis and secretion of cellular fibronectin by fat-storing cells in vitro.
      ED1 positive sequences specific for cellular fibronectin and absent in plasma
      fibronectin were detected within the total RNA of fat-storing cells. Cellular
      fibronectin synthesis was severalfold enhanced in "activated" vs. "resting" fat
      storing cells. Treatment of fat-storing cells with transforming growth factor
      beta 1 resulted in a dose dependent increase of fibronectin synthesis. In
      contrast, interferon gamma inhibited the synthesis of fibronectin. The
      stimulation of fibronectin synthesis by transforming growth factor beta 1 and the
      inhibition by interferon gamma might be of importance for pathophysiology and
      therapy of liver fibrogenesis.

PMID- 1397890
TI  - Fibrosing cytolytic liver failure secondary to recurrent hepatitis B after liver
      transplantation.
AB  - Four patients who underwent transplantation for hepatitis B virus-related liver
      disease developed rapidly progressive liver failure attributable to recurrent
      hepatitis B disease typified by hyperbilirubinemia and distinctive hepatocyte
      ballooning and progressive fibrosis consistent with recently reported fibrosing
      cholestatic hepatitis. Among these four patients, the mean interval from
      transplantation to redocumentation of hepatitis B surface antigen (HBsAg) and
      hepatitis B e antigen (HBeAg) was 5 months, to development of malaise and
      jaundice 6 months, to histological diagnosis 7 months, and to graft failure 8
      months. The only patient who underwent retransplantation had accelerated
      recurrence of the same syndrome with biopsy documentation 1 month later and graft
      failure 2 months later. Distinctive histological features included confluent
      hepatocellular ballooning and progressive periportal fibrosis followed by lobular
      collapse over 4-6 weeks without significant inflammation. Immunohistochemical
      staining showed marked HBsAg and hepatitis B core antigen (HBcAg)
      immunoreactivity. The rapid development of cytolytic hepatocellular necrosis and
      lobular collapse with prominent HBcAg immunoreactivity without significant
      inflammation suggests a cytolytic rather than immune pathogenesis for this unique
      and devastating form of recurrent hepatitis B that might better be termed
      "fibrosing cytolytic hepatitis."

PMID- 1397892
TI  - Manometric characteristics of cervical dysphagia in a patient with the Kearns
      Sayre syndrome.
AB  - The manometric findings of deglutitive pharyngoesophageal function in a patient
      with the Kearns-Sayre syndrome and cervical dysphagia are described. These
      findings indicate that striated muscles of the pharynx, upper esophageal
      sphincter (UES), and proximal esophagus are involved. Near absence of pharyngeal
      peristalsis, abnormally low UES resting pressure, and absence of proximal
      esophageal peristalsis characterize the manometric findings in this patient. It
      is conceivable that in mild cases, a combination of various degrees of severity
      of the above findings may exist.

PMID- 1397893
TI  - Fatal neonatal liver failure and mitochondrial cytopathy: an observation with
      antenatal ascites.
AB  - Mitochondrial cytopathies are multisystemic diseases of extremely variable
      expression caused by a deficiency in oxidative phosphorylation. Only five cases
      of neonatal liver failure in the context of mitochondrial cytopathy have been
      reported, with incomplete morphological data of the liver in three. In the case
      presented here, ascites had been diagnosed prenatally and liver failure was
      particularly severe (factor V less than 15% with fatal coma the fourth day).
      Histologically there were incomplete cirrhosis, microvesicular steatosis, major
      canalicular cholestasis with proliferative neocholangioles, and bile duct
      thrombi. There were also some iron pigments in the periportal area and partial
      glycogen depletion. By electron microscopy, mitochondria in numerous hepatocytes
      appeared abnormal with occasional cristae in a fluffy matrix, some containing
      dense inclusions. Study of respiratory chain activity showed a defect in
      cytochrome c oxidase (complex IV), revealed by oxygraphic measurement on fresh
      muscle biopsy and confirmed by spectrophotometric enzymatic assays performed on
      muscle and liver homogenates. The association of neonatal liver failure with
      hyperlactacidemia warrants investigation into a deficiency in oxidative
      phosphorylation.

PMID- 1397894
TI  - Bloody diarrhea, jaundice, and sepsis in a septuagenarian.

PMID- 1397895
TI  - Hepatitis B after liver transplantation: new names for unusual presentations.

PMID- 1397896
TI  - Intrahepatic portacaval shunts: a new era?

PMID- 1397897
TI  - Injection therapy for bleeding ulcers: which solution is best?

PMID- 1397899
TI  - Hypergastrinemia and colonic neoplasia: coincidental or related?

PMID- 1397900
TI  - Braving the elementals in Crohn's disease.

PMID- 1397898
TI  - Prognosis in chronic liver diseases: Cox models, quantitative liver function
      tests, or both?

PMID- 1397901
TI  - Septicemia after endoscopic retrograde cholangiopancreatography.

PMID- 1397903
TI  - Is prostacyclin synthesis greater in cirrhotic patients?

PMID- 1397902
TI  - Quantitative discrimination of glomerular B and C receptors.

PMID- 1397904
TI  - Smoking and adenomatous colorectal polyps.

PMID- 1397905
TI  - The American Motility Society meeting. Lake Tahoe, California, September 13-17,
      1992. Abstracts.

PMID- 1397906
TI  - The effect of guidewires during electrosurgical sphincterotomy.
AB  - We describe six electrosurgical incidents and one complication which occurred
      during guidewire-assisted sphincterotomy. Studies were conducted on three types
      of guidewires: Teflon painted, Teflon sheathed, and polymer coated. Scanning
      electron micrographs demonstrated surface imperfections in the painted Teflon
      guidewire coating, which allowed for potential electrical short circuits between
      cutting wire and guidewire through a septal defect in a double channel catheter.
      Septal defects were found in 25% (1 of the 4 tested) of the factory fresh
      sphincterotomes that were used in this study, and in 10% (6 of 57) of those used
      clinically. Induced current (capacitively coupled) present on the guidewires was
      measured at 13 to 30 mA for typical sphincterotomy settings. The induced current
      on sheathed guidewires, without any insulation defects, was measured at less than
      1 mA at typical operating powers. As both short circuits and induced currents
      place the patient at risk for burns or perforation at the distal end of the
      guidewire, we suggest the use of a Teflon-sheathed rather than Teflon-painted
      guidewire, if the wire is to be left in place during sphincterotomy. The Teflon
      sheath offers the thickest insulation, a very low probability of surface defects,
      and therefore a high index of safety.

PMID- 1397907
TI  - Mechanical lithotripsy of large gallstones: correlation with CT characteristics.
AB  - The CT characteristics of gallstones were correlated with mechanical forces
      required to fragment calculi in vitro. Forty-two gallstones > or = 11 mm in
      largest diameter were subjected to in vitro CT scanning and categorized as
      isodense, faint, laminated, rimmed, or dense as compared with saline. A
      mechanical lithotripter, attached to a dynamometer, was utilized simulating in
      vivo technique to accomplish lithotripsy. Significantly more force was required
      to fracture CT-dense (p < 0.02) and CT-rimmed (p < 0.05) gallstones than was
      required to fracture CT-isodense gallstones.

PMID- 1397908
TI  - Clinical features and endoscopic management of Dieulafoy's disease.
AB  - The experience of a specialized management team using urgent endoscopy in the
      management of acute gastrointestinal bleeding from Dieulafoy's disease is
      presented. Dieulafoy's disease was found in 19 of 1124 consecutive patients with
      upper gastrointestinal bleeding. Most patients with Dieulafoy's disease were
      elderly men with severe acute upper gastrointestinal hemorrhage. Endoscopic
      diagnosis was possible in all patients, but required multiple endoscopies in 37%.
      The lesions were in the proximal stomach (79%) and duodenal bulb (21%).
      Endoscopic therapy included epinephrine injection, then heater probe coagulation
      in 17 patients, bipolar electrocoagulation in 1, and Nd:YAG laser
      photocoagulation in 1. Endoscopic therapy was successful in 18 patients (95%);
      one patient had successful surgery after endoscopic therapy failed. There were no
      deaths due to bleeding and no endoscopic complications. Dieulafoy's disease is an
      unusual cause of acute gastrointestinal bleeding. Endoscopic diagnosis is
      sometimes difficult, but primary endoscopic therapy is safe, successful, and
      should be attempted.

PMID- 1397909
TI  - Barrett's esophagus: lack of association with adjuvant chemotherapy for localized
      breast carcinoma.
AB  - This study was designed to prospectively, endoscopically, and histologically
      determine the prevalence of Barrett's esophagus in patients who had received
      adjuvant chemotherapy for localized breast carcinoma. Fifteen white women who
      received cyclophosphamide, methotrexate, and 5-fluorouracil (N = 8) or
      cyclophosphamide, adriamycin, and 5-fluorouracil (N = 7) chemotherapy underwent
      esophagogastroduodenoscopy and esophageal biopsy a mean 31.1 months (median, 11
      months) after completion of full-course chemotherapy. Twelve of 15 patients had
      experienced oral ulcerations, diarrhea, or odynophagia during chemotherapy. In no
      patient was Barrett's esophagus identified endoscopically or histologically. This
      study fails to demonstrate an increased prevalence of Barrett's esophagus in
      breast carcinoma patients who had received adjuvant chemotherapy.

PMID- 1397910
TI  - Accuracy of assessment of the extent of examination by experienced
      colonoscopists.
AB  - One hundred colonoscopies were done. The colonoscopist noted whether the cecum
      had been intubated as well as the markers used to make this determination. With
      the colonoscope in position at maximum penetration, a radiologist independently
      determined its position using fluoroscopy, with a contrast agent delivered
      through the colonoscope. The cecum was entered in 86 of 100 cases. The tip of the
      colonoscope was at the level of the ileocecal valve in nine additional cases; the
      colonoscopist judged that the cecum was well seen in five of these nine. In one
      case, the colonoscopist overestimated the extent of the examination when
      transillumination in the right lower quadrant was the only confirming marker.
      When the more reliable markers (ileocecal valve, appendiceal orifice, converging
      indentations of the taenia coli in the cecal pole) were seen, no errors were
      made. Experienced colonoscopists are accurate in assessing the extent of
      colonoscopy and fluoroscopic confirmation is not routinely needed. When reliable
      markers are not seen during the examination, a barium enema, preferably with air
      contrast, should be done.

PMID- 1397911
TI  - Pain following colonoscopy: elimination with carbon dioxide.
AB  - Fifty-six patients have been examined in a prospective randomized study on the
      effects of air and carbon dioxide on post-procedural discomfort following
      colonoscopy. A significant reduction in post-procedural pain was observed at 6
      hours (p = < 0.0005) and was still present the next day (p = 0.01). This was
      associated with a difference in the grading of flatus at 6 and 24 hours (p = <
      0.0001 and < 0.05, respectively). An abdominal radiograph 1 hour after the
      procedure showed minimal gas in the CO2 patients, while the patients who had air
      showed distention of large and small bowel (p = < 0.0001 and < 0.01,
      respectively). Seventeen of 29 patients who had air suffered post-procedural
      pain, compared with 2 of 27 of the CO2 patients. Fifty-seven percent of the
      patients who were given air had colonic diameters over 6 cm on a 1-hour post
      colonoscopy radiograph and 18% over 10-cm diameter. Provision by equipment
      manufacturers of simple and safe devices for routine delivery of CO2 for lower
      gastrointestinal endoscopy is long overdue.

PMID- 1397912
TI  - Endoscopic diagnosis of colonic endometriosis.
AB  - Involvement of the colon or rectum with endometriosis is uncommon but may be a
      cause of gastrointestinal symptoms such as diarrhea, pain, and bleeding. To
      determine whether endoscopy has a role in evaluating endometriosis of the colon,
      we reviewed all cases of endometriosis undergoing colonic resection from 1984 to
      1989. There were nine patients, six of whom had intermittent hematochezia. All
      had lesions detected at endoscopy described as a polyp, mass, or stricture. Five
      of the six patients with symptoms of hematochezia had mucosal involvement in the
      resected specimen. Four of these five had a visible lesion at endoscopy with
      endometriosis on biopsy. The three patients without hematochezia had no mucosal
      endometriosis in the resected colonic specimen or endometrial tissue on biopsy.
      In patients with colonic endometriosis and hematochezia, endoscopy and biopsy can
      confirm the diagnosis of colonic endometriosis.

PMID- 1397913
TI  - Endoscopic diagnosis of segmental colonic tuberculosis.
AB  - We report colonoscopic findings in 29 proven cases of segmental colonic
      tuberculosis. The colonoscopic appearances of tuberculosis included: mucosal
      nodules and ulcers, stricture with nodules and ulcerations, and mucosal nodules
      with or without pseudopolypoid folds. In 12 (41%) of 29 patients colonoscopy
      biopsies enabled a histologic diagnosis to be made on the basis of typical
      granulomas. Culture of biopsy tissue on Lowenstein Jensen media isolated
      Mycobacterium tuberculosis in six (40%) of 15 patients. Combined histologic and
      bacteriologic evaluation established the diagnosis in 60% of patients. We
      conclude that even though target biopsy is an effective method of diagnosis, anti
      tuberculous chemotherapy may be started on the basis of the endoscopic appearance
      if there is a high clinical suspicion of tuberculosis.

PMID- 1397914
TI  - Serum electrolyte, mineral, and blood pH changes after phosphate enema, water
      enema, and electrolyte lavage solution enema for flexible sigmoidoscopy.
AB  - Hypertonic sodium phosphate (Fleet) enema is a commonly used preparation for
      fiberoptic flexible sigmoidoscopy. Unfortunately, Fleet has been associated with
      complications in children and adults. The purpose of this study was to compare
      the serum electrolytes, mineral, and blood pH changes before and after the
      administration of Fleet with water and polyethylene glycol electrolyte lavage
      solution (Golytely) as enemas in an adult population undergoing flexible
      sigmoidoscopy. Sixty-six patients were randomized in a double-blind fashion to
      receive two enemas of either Fleet (N = 22), water (N = 20), or Golytely (N =
      24). The cleansing ability was graded from 1 to 4 (1 = poor, 4 = excellent). The
      Fleet had significantly better optimal cleansing efficacy compared with water (p
      < 0.05) but not to Golytely (p > 0.05). There was a significant increase in the
      serum phosphorus in the Fleet group compared with water (p < 0.001) or Golytely
      (p < 0.001). However, absolute serum phosphorus values after Fleet enema always
      remained within normal range in all but one patient. The changes in other
      electrolytes, minerals, and venous pH were insignificant.

PMID- 1397915
TI  - Low sodium solution for colonic cleansing: a double-blind, controlled, randomized
      prospective study.
AB  - The standard polyethylene glycol electrolyte solution for colonic cleansing has a
      salty unpleasant taste resulting in limited patient acceptance. Introduced as a
      major advance allegedly providing a distinctly better taste, a new low sodium
      cleansing solution was recently described. In a double-blind controlled fashion,
      66 colonoscopy outpatients were interviewed about general palatability and
      tolerance of the solution they had ingested for the preparation of endoscopy.
      Preparation quality was assessed endoscopically. Similar results were obtained
      for both solutions concerning palatability, tolerance, and cleansing quality.
      Furthermore, a small quantity of both solutions was tasted and directly compared
      for taste qualities before endoscopy. Fifty-one and one-half percent of patients
      preferred the new solution and 48.5% preferred the standard solution or had no
      preference (not significant). Of the patients, 39.2% were unable to differentiate
      between the more and the less salty solution. Moreover, 39.6% of patients
      preferred the solution they judged more salty. We conclude that the new low
      sodium lavage solution is not superior to the standard solution regarding patient
      acceptance, compliance, and cleansing quality. Thus, the reduction of salt
      concentration does not appear to be the appropriate approach to improve patients
      compliance with colonic cleansing solutions.

PMID- 1397916
TI  - Effects of endoscopic injection sclerotherapy on portal hypertensive gastropathy:
      a prospective study.
AB  - The effect of endoscopic injection sclerotherapy (EIS) for esophageal varices on
      portal hypertensive gastropathy (PHG) was investigated in 137 patients who
      underwent EIS from July 1987 to March 1990. Two groups, PHG(+) (N = 35) and PHG(
      ) (N = 102) were distinguished by endoscopic findings obtained before EIS. PHG
      was classified into four grades by endoscopy scored as 0, 1, 2, or 3. The PHG
      score significantly worsened after EIS (p < 0.01), and PHG became worse 6 to 9
      months after the eradication of varices followed by gradual improvement.
      Recurrent small veins, which required additional EIS, appeared more frequently in
      the PHG(+) group (p < 0.05). New gastric varices appeared or gastric varices
      enlarged after EIS more frequently in the PHG(+) group (7 patients, 20.0%) than
      in the PHG(-) group (12 patients, 11.8%), but this was not statistically
      significant. Thus, frequent endoscopy after EIS is needed with special attention
      directed to development of PHG and gastric varices, especially for patients with
      PHG prior to treatment.

PMID- 1397918
TI  - A new double lumen, direct irrigation injection therapy catheter.

PMID- 1397919
TI  - Transnasal endoscopic technique for feeding tube placement.

PMID- 1397917
TI  - Pancreatic rendez-vous.

PMID- 1397920
TI  - A new endoscopic technique for introducing pneumatic dilators in patients with
      achalasia.

PMID- 1397921
TI  - Two fatal complications related to gastrostomy "button" placement.

PMID- 1397922
TI  - Endoscopic management of a pancreatic pseudocyst during pregnancy.

PMID- 1397923
TI  - Cystic duct clip migration into the common bile duct: a complication of
      laparoscopic cholecystectomy treated by endoscopic biliary sphincterotomy.

PMID- 1397924
TI  - Surgical clip as a nidus for common bile duct stone formation and successful
      endoscopic therapy.

PMID- 1397925
TI  - Ileal Kock pouch obstruction secondary to retained medicoliths.

PMID- 1397926
TI  - Laparoscopic diagnosis of retractile mesenteritis.

PMID- 1397927
TI  - Gallstone ileus treated by electrohydraulic lithotripsy.

PMID- 1397928
TI  - Laser-induced transient regression of Barrett's epithelium.

PMID- 1397929
TI  - Pre-cut papillotomy.

PMID- 1397930
TI  - Safety first, simplicity second.

PMID- 1397931
TI  - A/S/G/E presidential address--1992.

PMID- 1397932
TI  - Advanced endoscopic training: teaching us older dogs some new tricks.

PMID- 1397933
TI  - Costs in the evaluation of dyspepsia.

PMID- 1397934
TI  - Marked wire-guided esophageal dilation and the need for fluoroscopy.

PMID- 1397935
TI  - Aluminum phosphide-induced gastroduodenitis.

PMID- 1397936
TI  - Gastrointestinal bleeding after cold biopsy.

PMID- 1397937
TI  - Endoscopic examination of the common hepatic duct and cholangiography in a
      patient with previous Roux-en-Y hepaticojejunostomy and Billroth I operation.

PMID- 1397938
TI  - Bleeding from a jejunal hemangioendothelioma.

PMID- 1397939
TI  - [Myelomeningocele--what can be done? Aids for evaluating rehabilitation from the
      orthopedic viewpoint].
AB  - Shortly before or shortly after the delivery of a child suffering from congenital
      paraplegia (myelomeningocele or spina bifida) the obstetrician is obliged to give
      advice as to what will follow after neurosurgical closure of the cele and
      shunting of the hydrocephalus. The parents' understanding of therapy and
      integration of the patient is developed to assess and utilise the future chances
      of the disabled child. Integration of children with congenital paraplegia is
      performed by an interdisciplinary team of therapists. However, the obstetrician's
      advice is of great value in preparing the parents for their decision for or
      against total care post partum. They must in fact be fully aware of the chances,
      that the disabled child actually has with regard to integration in life, and of
      what can be done in this respect. Besides the neurological, paediatric and
      urological care, it is the task of the orthopaedist to preserve or even to
      improve verticalization and mobility in paraplegic patients. In this manner he
      exercises an influence on the quality of life of the disabled children and on
      their social integration. Improvement and further development of physiological
      orthoses for walking enable even children suffering from a thoracic level of
      paralysis to walk independently and to achieve integration into society.
      Orthopaedic aspects of integration must be part of the information given to the
      parents by the obstetrician, so that they may be able to assess in what way their
      disabled children can participate in the future at various levels of everyday
      life.

PMID- 1397940
TI  - [Follow-up of 551 patients with node-negative breast cancer].
AB  - To evaluate the prognostic significance of established clinical, histological,
      and biochemical factors, we examined the survival data of 551 node-negative
      breast cancer patients. At a median follow-up of 5 years, we found 114
      recurrences, 79 of them at distant sites. 41 patients died. 84 patients with less
      than 8 examined lymph nodes, adjuvant systemic treatment, or treatment differing
      from standard procedures, had a statistically significant shorter overall
      survival and were excluded from further analysis. With regard to relapse-free and
      overall survival univariate and multivariate analyses of the remaining 467
      patients revealed only few factors with prognostic significance. In multivariate
      analysis of overall survival by the Cox regression model, statistically
      significant prognostic value was limited to three factors: lymphangiosis
      carcinomatosa (relative risk 4.8, 95%-confidence interval 2.0-11.7),
      postmenopausal status (0.38, 0.17-0.84), and positive progesterone receptor
      status (0.37, 0.14-1.0). In addition, there was a trend (p = 0.075) of prolonged
      survival in patients with Bloom and Richardson grade I cancers. The few
      prognostic factors found were able to identify patients with very good, as well
      as very bad prognosis. However, for the majority of node-negative breast cancer
      patients, estimation of prognosis remains unsatisfactory. Therefore, further
      independent prognostic factors are necessary.

PMID- 1397941
TI  - [Recurrence of vulvar cancer--treatment, experiences and results].
AB  - At the University Hospitals of Heidelberg (1970-1988) and Homburg/Saar (1988
      1990), 182 patients with vulvar carcinoma were treated. 51 patients had a
      recurrence of vulvar carcinoma and 21 patients showed a persistence of this
      tumour. 19 women had a second recurrence of vulvar disease. In these cases,
      therapy ranged from local surgery to exenteration, depending on the site and
      tumour extension. 18 patients underwent successful reconstructive surgery.
      Prognosis was better in cases with local recurrence in comparison to distant
      sites of metastatic progression (i.e. inguinal nodes or disseminated disease) (p
      less than 0.001). The five-year survival (after diagnosis of recurrent disease)
      for patients with early onset of recurrence (less than 20 months after initial
      therapy) was 28% compared to 68% for patients with late onset of recurrent
      disease (p less than 0.01).

PMID- 1397942
TI  - [Status of fractionated abrasion and vaginal endocervical cytology in diagnosis
      of endometrial cancer].
AB  - The predictive value of cervical cytology and uterine curettage in 150
      endometrial carcinoma was investigated. Cytology proved negative in 56% of all
      carcinomas and in 42.2% of those in stage 2 or 3. Uterine curettage was found to
      have a false-negative rate of 6%, endocervical curettage of 5.3%. By contrast, we
      found a high false-positive rate of 70.8% for endocervical curettage. 13.2% of
      the 129 endometrial carcinoma stage 1 had a false-positive endocervical fraction.
      No residual disease was found in 4.7% of all 150 hysterectomy specimens. Negative
      cervical cytology seems to be a reasonably good predictor of actual cervical
      involvement, if a positive endocervical curettage is to be interpreted.

PMID- 1397943
TI  - [The significance of prostaglandin F2 alpha (PGFM)--and plasma oxytocin level in
      patients with premature labor].
AB  - In the present study, plasma oxytocin and prostaglandin F2 alpha metabolite
      (PGFM) concentrations were measured in 46 patients admitted for preterm labour.
      Gestational age ranged from 20-34 weeks. Samples were collected 12 hours before
      and after initiation of tocolysis. Patients with a premature rupture of the
      membranes and/or intra-amniotic infection were excluded in this study. There was
      a significant difference in the oxytocin (p = 0.05) and PGFM levels (p = 0.007,
      after 12 hours: p = 0.004) between a control group without preterm labour and
      women with preterm labour. No differences were seen between the successfully
      treated (delivery more than 5 days after start of tocolysis) and the failure
      group. There was no significantly different increase or decrease in PGFM and
      Oxytocin plasma levels between treatment failures and successfully treated
      patients.

PMID- 1397944
TI  - [Cytogenetics of unfertilized or uncleaved oocytes within the scope of in vitro
      fertilization. Relations to hormone content of follicular fluid].
AB  - Constituents of the follicular fluid (FF) have been suspected to influence
      fertilizability and cytogenetic constitution of human oocytes. Therefore, we
      analysed the FF concentrations of 17 beta-estradiol (E2), progesterone (P),
      testosterone (T), and prolactin (PRL) of 114 oocytes recovered for in vitro
      fertilisation (IVF). 46 of these oocytes were fertilised and transferred to the
      maternal uterus. Among the unfertilized gametes, 27 were not analysable. 30 were
      normal haploid, and 11 were classified as abnormal. There was no significant
      difference between fertilised and unfertilized oocytes for FF concentrations of
      E2, P, T, and PRL and for the E2/P ratios. Similarly, we detected no significant
      difference between normal and abnormal oocytes for these parameters.

PMID- 1397945
TI  - [Steroid and protein hormone concentrations in serum and follicular fluid after
      stimulation for in vitro fertilization].
AB  - Sixty patients with tubal infertility were stimulated for IVF with a fixed
      schedule consisting of clomiphene and pure follicle stimulating hormone. They
      responded with an optimal estradiol increase and 2 to 4 embryos were transferred.
      Conception cycles (n = 17) could be differentiated from non-conception cycles (n
      = 43) by serum estradiol, serum progesterone, the serum progesterone/estradiol
      ratio and serum LH concentrations. Testosterone, androstenedione and FSH in serum
      and follicular fluid showed no significant relation to a possible therapy
      outcome. We conclude from our findings, that, during the peri-implantation
      period, certain LH patterns followed by an optimal progesterone/estradiol-ratio
      in the serum support an embryo survival after transfer to the uterus.

PMID- 1397946
TI  - [Spontaneous conception after laparoscopic coagulation of the ovarian surfaces in
      a patient with primary normogonadotropic hyperandrogenemic amenorrhea].
AB  - A patient with primary amenorrhoea was kept under hormonal replacement therapy
      and oral contraceptives since the age of sixteen. At the age of 30 she first
      consulted the endocrinologist because of infertility after one year of "post-pill
      amenorrhoea". This first hormone check detected a severe hypertestosteronaemia
      (1.3 ng/ml). During four stimulation cycles using gonadotropins she showed a
      polyfollicular reaction and finally developed a hyperstimulation WHO II. During
      the following cycle she underwent hystero- and laparoscopy; laparoscopic
      electrocoagulation of the ovarian surface (LEOS) was carried out during this
      treatment. She subsequently conceived spontaneously twice.

PMID- 1397947
TI  - [Infiltrating tubo-ovarian abscess in IUD-associated actinomycosis].
AB  - We report on a case of a 55-year old patient with a great adnexal tumour (10 x 5
      x 8 cm), on the left side with infiltration of the bladder and the pelvis with
      recurring urinary retention in the kidney. Histological examination revealed an
      intrauterine device-associated actinomycosis. Following a 6-month high dose
      penicillin therapy, the abdominal hysterectomy with adnexectomy and partial
      resection of the bladder with new implantation of the ureter (Boari) was
      performed. The postoperative period was uneventful, the urogram normal.

PMID- 1397948
TI  - [Struma ovarii maligna].
AB  - Benign and malignant struma ovarii are very rare ovarian teratomas. Specific
      therapy guidelines should be established. A case of a malignant struma ovarii is
      presented and results of therapy discussed.

PMID- 1397949
TI  - [Mastopathy in partial testicular feminization].
AB  - We report on a patient with synchrony of mastopathic alterations and incomplete
      testicular feminization. In the 54-year old patient, typical climacteric
      complaints as well as mastopathy-associated symptoms occurred. After orchiectomy
      and subsequent oestrogen substitution, clinical symptoms disappeared.

PMID- 1397950
TI  - [Harmful substances and infertility. Substances of abuse].
AB  - Contaminants exercise an influence on different levels of reproduction, resulting
      in disturbances of the cycle, abortion and diverse complications during pregnancy
      among women, whereas, in the case of men, alterations of the spermiogram have
      been observed. Numerous unfavourable influences on reproduction are known from
      toxins such as alcohol, cigarettes and caffeine. By means of a survey of
      references and own results, these secondary effects are demonstrated in order to
      warn couples of the serious consequences with regard to the abuse of toxins, e.g.
      coffee, tobacco etc., when seeking advice in questions of infertility and
      pregnancy.

PMID- 1397951
TI  - [Clinical and immune hematologic problems in prenatal prevention of Rhesus
      sensitization].
AB  - Various studies have provided impressive evidence of the efficacy of antenatally
      administered anti-D in the prevention of rhesus (D) alloimmunisation in rhesus
      negative women. However, possible clinical and immunohaematological problems
      associated with this prophylactic therapy have received little attention. We
      describe perinatal and immunohaematological problems, which occurred in four
      cases after antenatal rhesus prophylaxis. Classical immunohaematological
      techniques were employed, to detect and specify irregular red cell antibodies. It
      was found, that the antenatal administration of anti-D could mask sensitization
      to other red cell antigens or the production of maternal immune anti-D antibodies
      later in pregnancy. A further problem encountered was that of neonates with a
      positive direct Coombs' test (the uncertainty in the individual case being,
      whether this is a result of the antenatal administration of anti-D) and marked
      hyperbilirubinaemia. Antenatal immunoprophylaxis for rhesus disease can give rise
      to immunohaematological and clinical findings, of which the interpretation is
      extremely difficult and requires intensive cooperation between the obstetrician,
      neonatologist, and haematologist/clinical biochemist.

PMID- 1397952
TI  - [Three-dimensional ultrasound imaging of benign and malignant breast tumors-
      initial clinical experiences].
AB  - Previous experimental and clinical studies showed, that three-dimensional (3-D),
      i.e. dynamic spatial reconstruction of 2-D ultrasound images is feasible. A
      rotating acoustic plane helps to visualise the cross-sections serially and in a
      coordinated manner. When reconstructing the 2-D ultrasound images, surface
      reconstruction from planar contours of each cross-section is performed (so that
      the organ limits are defined) and the cross-sectional pictures are reconstructed
      into 3-D organ images. This approach had been described by the authors on a
      previous occasion. Another step forward is "transparent" spatial imaging
      eliminates the source of error involved in contouring. It is important to
      emphasise, that the 3-D system now described by the authors, yields a spatial
      image of the organ in question, and does not just present 3 planes of the organ
      (some authors have been claiming, that such an imaging method is also three
      dimensional). Our system enables the imaging of several cross-sectional planes
      cut through the spatially calculated organ. This results in cross-sections, which
      cannot be performed by conventional sonography, thus disclosing new perspectives
      and possibilities. In the present article, the authors describe a clinical pilot
      study in the diagnosis of carcinomas of the breast. In our opinion, 3-D imaging
      of the tumours enables the physician to diagnose the status of the tumours; this
      is demonstrated by the examples of 35 malignant and benign tumours of the breast.
      In 95% of the cases of malignant tumours and 80% of the benign tumours, the
      diagnosis proved correct. This paper describes the fundamental possibilities and
      limitations of the new method.

PMID- 1397954
TI  - [Primary, papillary serous carcinoma of the peritoneum; a report of experiences].
AB  - A total of fourteen patients with primary papillary serous carcinoma of the
      peritoneum (PPSCP) were treated at the Department of Obstetrics and Gynaecology
      of the University of Graz between 1980 and 1991. The presence of tumours from
      other sites, particularly the pancreas and the ovary, had been excluded. Due to
      extensive spreading of the disease mainly in the upper abdomen, only seven of the
      14 patients underwent exploratory laparotomy. The median overall survival time
      was 10 months (range, 1-28 months). These results are due to the extent of
      spreading of the disease at diagnosis, and also to the fact, that optimal
      cytoreductive surgery was possible only in four of the 14 patients. The four
      patients with optimal cytoreduction showed a better survival than those, who
      underwent less radical surgery. These results seem to indicate, that, as in
      primary ovarian cancer, the amount of residual disease may be an important
      prognostic determining factor in PPSCP.

PMID- 1397953
TI  - [Prognostic significance of the CA 125 half-life for the further outcome of
      ovarian cancer].
AB  - Since only approx. 30% of patients with ovarian carcinoma present themselves in
      the early stages, and as a result of the lack of effective screening methods,
      primary interest has been applied to the improvement of the treatment quality in
      the later stages. Improvement of therapeutic strategies implies an adaptation of
      specific characteristics of the patient and the tumour. For instance, in cases of
      primary progression during chemotherapy, it is not justified to continue an
      aggressive treatment, which causes additional serious side effects. Surprisingly,
      it has not been possible, to utilize established or suspected prognostic factors
      for treatment strategies in ovarian cancer. This might result, in part, from the
      uncertainty of criteria such as stage of disease, residual tumour and
      histological grading. The single most relevant prognostic factor today is the
      residual tumour mass. In 1988 van der Burg suggested for the first time a
      potential prognostic relevance of the CA 125 half-life. This study was designed,
      to investigate the use of CA 125 half-life in therapeutic strategies. From
      January 1984 to June 1990, 346 patients with primary ovarian cancer were treated
      at our institution. Preoperative CA 125 levels were determined in 292 patients;
      in 220 patients the levels were complete for a period of more than 6 months so
      that the CA 125 half-life could be calculated. Survival times of patients with a
      half-life of less than 20 days were significantly (p less than 0.0001) different
      from patients with a half-life of more than 20 days.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1397955
TI  - [Retrospective comparative study of the treatment of tubal pregnancy by
      pelviscopic surgery or prostaglandin injection].
AB  - The incidence of tubal pregnancy has been increasing in recent years. The
      improvement in diagnostic procedures leads to an early detection of tubal
      pregnancies. As a result, conservative treatment modalities are more feasible
      today. In this study, we compared the treatment of tubal pregnancy by means of
      locally applied prostaglandin with pelviscopic surgery. 75 patients with an early
      tubal pregnancy were included in each group. The comparison between the two
      groups showed, that prostaglandin treatment has a higher failure rate, than
      treatment by pelviscopic surgery. However, postoperative fertility indicated
      better results in the prostaglandin treated patients.

PMID- 1397956
TI  - [Adolescent primiparous women, 17-years-old and younger].
AB  - Between January 1, 1983 and June 30, 1991, 107,420 primiparae were recorded in
      the Swiss Statistics, which cover approx. 60 hospitals. 573 primiparae were 17
      years of age or less (= Group I). The control group consisted of 106,855
      primiparae between 18 and 35 years of age (Group II). Comparison of these 2
      groups showed the following results: A significantly higher risk in prematurity
      in Group I. There was no significant difference in perinatal mortality or in
      birth weight under 2,500 g. A significantly lower rate of caesarean sections and
      of surgical assisted vaginal deliveries were recorded in Group I.

PMID- 1397957
TI  - [Fetal outcome of premature infants less than 1,500 g birth weight with special
      reference to surfactant requirements].
AB  - The objective of our study was to examine therapeutic success within a study
      group of 108 premature babies weighing less than 1500 g at birth. The foetal
      outcome was divided according to intrauterine betamethasone administration,
      method of birth and surfactant requirement. 59 of the babies did not require a
      surfactant factor, because within 12 hours it was possible, to reduce respiration
      to an O2 partial pressure of 20%. In 49 of the premature babies, this was not
      possible, and therefore, surfactant substitution was required, whereby this
      subject group was divided into surfactant responders and surfactant non
      responders. In addition, we examined the influence of the method of birth on
      later survival and the occurrence of intraventricular haemorrhages in the
      children. A noticeably higher survival rate was determined in 81% of the
      children, born via Caesarean section, compared with 63% of premature babies, born
      via vaginal delivery. Likewise, detectable intraventricular haemorrhages (IVH)
      were significantly lower amongst premature babies delivered via Caesarean section
      (25%) than those delivered vaginally (37.5%). A considerable improvement in
      survival rates and a reduction in IVH was achieved by means of completed lung
      maturation with betamethasone (16 mg in 48 hours). 62% of premature infants with
      completed prepartal lung maturity did not require the administration of a
      surfactant due to the favourable respiratory situation. However, for those cases,
      where it was no longer possible to conduct lung maturation, only 46% did not
      require surfactant substitution. Therefore, it would appear advisable, to delay
      the delivery of premature babies weighing less than 1500 g in order to carry out
      lung maturity treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397958
TI  - [The effect of smoking on the resistance index of the umbilical artery and the
      middle cerebral artery].
AB  - 23 healthy smokers with uneventful singleton pregnancies underwent Doppler-flow
      measurements of the foetal umbilical artery and middle cerebral artery before and
      ten minutes after smoking one cigarette. In both arteries the resistance indices
      (RI) did not change significantly. Maternal mean arterial blood pressure and
      heart rate increased significantly after the smoking of the cigarette. Neither
      the group with an RI increase of greater than or equal to 5% in the foetal
      umbilical artery (n = 7) nor the group with an increase of the RI in the foetal
      umbilical artery and, at the same time, a decrease of the RI in the arteria
      cerebri media (n = 5), showed a significant difference concerning maternal
      haemodynamic parameters and the number of cigarettes smoked before and during
      pregnancy. The results suggest, that the smoking of one cigarette in uneventful
      pregnancy does not produce acute haemodynamic effects in the foetus.

PMID- 1397959
TI  - [Spontaneous abortion after vaginal hemorrhage in intact early pregnancy--an
      etiologic analysis].
AB  - 283 patients with vaginal bleeding before a gestational age of 16 weeks and
      positive foetal heart action were followed up by mean of ultrasound examination
      until termination of pregnancy. 18 pregnancies (7.5%) ended in spontaneous
      abortion. 44.4% of these abortions showed histological parameters of an
      infection, and in 16.6%, a sub-chorionic haematoma was diagnosed. In one case
      only a chromosomal anomaly (triploidy), was found. In 25 percent of the
      abortions, there was no evidence of histological abnormality. Since it could be
      demonstrated, that a bacteriological infection a possible cause of live abortions
      before 16 weeks of pregnancy, it could be concluded, that it might be possible to
      reduce live abortions by bacteriological examinations of the cervix and vagina
      followed by specific antibiotic treatment. If vaginal bleeding stopped during
      follow-up, the pregnancy outcome was normal.

PMID- 1397960
TI  - [Operation of acute dissecting aortic aneurysm in the 25th week of pregnancy
      using hypothermic extracorporeal circulation].
AB  - We report on a 24 + 2 weeks pregnant woman with Marfan's syndrome, who acutely
      developed a dissecting aortic aneurysm with aortic valve insufficiency. Emergency
      surgery was performed by using hypothermic extracorporeal circulation, whilst the
      aortic valve and ascending aorta were replaced by a synthetic graft. Foetal heart
      rates, continuously monitored by using Doppler ultrasound, were shown to be
      closely correlated with perfusion pressures. By applying perfusion pressures of
      90-100 mmHg, we were able to maintain foetal heart rates of approximately
      100/min. During the first postoperative day, the CTG was normal for gestational
      age and no contractions were noted. During the second postoperative night, the
      patient prematurely delivered a dead 820 g infant (Apgar score 0/0/0/0). In view
      of this case report, opportunities and problems associated with an application of
      extracorporeal circulation during pregnancy are discussed.

PMID- 1397961
TI  - [Fatal course of peracute fatty liver of pregnancy].
AB  - A fatal case of acute fatty liver of pregnancy (AFLP) is reported. After
      admission, the patient was delivered within 3 hours. Routine laboratory
      investigation revealed acute liver insufficiency with advanced coagulopathy.
      Despite substitution therapy, the severe coagulation defect progressed to lethal
      intracerebral bleeding. Advanced AFLP can only be satisfactorily diagnosed in
      time, if non-specific symptoms or icterus lead to studies of blood chemistry,
      especially liver function tests, coagulation parameters (including platelet
      count, fibrinogen, AT III), blood glucose and renal function (including uric
      acid). This will enable an adequate management of the patient. The clinical
      problem of AFLP still remains that of early diagnosis.

PMID- 1397962
TI  - [Deformed ear after chorionic villi biopsy. Is there a causal relationship?].
AB  - A case of a deformed ear following chorion villus sampling is described. The
      possibility of a relation between the described malformation and other
      malformations following chorion villus sampling is discussed.

PMID- 1397963
TI  - ["Production" and "reduction" of high degree multiple pregnancies from the legal
      viewpoint].

PMID- 1397964
TI  - [Limits of physician's treatment responsibility of severely handicapped newborn
      infants. Revised form].

PMID- 1397965
TI  - Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor
      and anti-AIDS activities from Cucurbitaceae plants.
AB  - 1. The biochemical characteristics and biological activities of eight
      Cucurbitaceae plant proteins designated trichosanthin (isolated from tubers of
      Trichosanthes kirilowii), beta-trichosanthin (isolated from tubers of
      Trichosanthes cucumeroides), alpha- and beta-momorcharins (isolated from seeds of
      Momordica charantia), momorchochin (isolated from tubers of Momordica
      cochinchinensis), luffaculin (isolated from seeds of Luffa acutangula) and luffin
      a and luffin-b (isolated from seeds of Luffa cylindrica), were reviewed. 2. The
      isolation procedures for all eight proteins are based on aqueous extraction,
      acetone fractionation and ion exchange chromatography. Ammonium sulfate
      precipitation and gel filtration are steps which may be included to improve
      purification. 3. The proteins are basic in nature and possess a molecular weight
      of approx. 30,000. All except trichosanthin are glycoproteins. The content of Asx
      and Glx residues is high. The N-terminal amino acid residue is Asp. Their amino
      acid compositions and N-terminal amino acid sequences are similar. 4. Circular
      dichroism spectroscopic studies revealed that trichosanthin, alpha- and beta
      momorcharins possess similar secondary but different tertiary structures. 5. Most
      of the proteins are immunologically distinct. 6. The proteins exhibit
      abortifacient, antitumor, ribosome inactivating and immunomodulatory activities.
      Trichosanthin manifests anti-human immunodeficiency virus activity.

PMID- 1397967
TI  - Effects of aminophylline on contractions and 45Ca uptake in isolated rat vascular
      smooth muscle.
AB  - 1. Aminophylline inhibited the contractions induced in rat isolated aorta by high
      K and noradrenaline (NA) as well as the transient contraction induced by NA in Ca
      free media and suppressed the spontaneous myogenic activity in portal vein
      segments. 2. Aminophylline had no significant effects on 45Ca influx in resting
      aorta but inhibited 45Ca influx stimulated by high K or NA. 3. It is concluded
      that aminophylline inhibited Ca entry through voltage- and receptor-operated
      channels and NA-induced Ca release from intracellular stores. A part of the
      vascular inhibitory effects of aminophylline may be mediated by a cAMP-dependent
      mechanism.

PMID- 1397966
TI  - Contractile effect and tissue content of arginine vasopressin in the urinary
      bladder of Brattleboro rats with hereditary diabetes insipidus.
AB  - 1. Urinary bladders from male rats of the Brattleboro strain with hereditary
      diabetes insipidus (DI) were analyzed for presence of immunoreactive arginine
      vasopressin (ir-AVP). Healthy rats were used as controls. 2. Bladders from the DI
      rats were heavier than controls. Concentration of ir-AVP was lower in DI
      bladders, but total amount of ir-AVP was similar to that in controls. 3. EC50
      values for the AVP concentration-response relations were similar for control and
      DI bladder strips. Maximum response to AVP relative to response to K+ high
      solution was lower in the DI group. 4. An AVP receptor antagonist that
      significantly blocked response to exogenous AVP had no effect on response to
      field stimulation. 5. We suggest that AVP is synthetized locally and that AVP is
      not the non-adrenergic non-cholinergic transmitter responsible for the atropine
      resistant contraction in rat bladder.

PMID- 1397968
TI  - Developmental changes in morphine and clonidine sensitivity of isolated chick
      oesophagus.
AB  - 1. Electrically evoked contractions of isolated newly-hatched and over 6 week-old
      chicks cervical oesophagus (pre-crop) were inhibited by morphine and clonidine in
      a dose-dependent manner. 2. The inhibitory effects of morphine and clonidine were
      antagonized by naloxone (3 x 10(-6) M) and yohimbine (10(-7) M), respectively. 3.
      IC50 for morphine was 1.01 x 10(-7) M for newly-hatched and 5.19 x 10(-6) M for
      adult chicks. 4. IC50 for clonidine was 2.34 x 10(-9) M for newly-hatched and
      1.19 x 10(-8) M for adult chicks. 5. These findings indicate a significant
      decrease in inhibitory effect of morphine and clonidine during developmental
      stages.

PMID- 1397969
TI  - Pancreastatin and its 33-49 C-terminal fragment inhibit glucagon-stimulated
      insulin in vivo.
AB  - 1. Pancreastatin, a 49 amino acid peptide derived from chromogranin A, has been
      shown to have an inhibitory effect on insulin secretion in the perfused pancreas
      and isolated islets. 2. We have studied the effect of pancreastatin on glucagon
      stimulated insulin release and the hyperglycemic of glucagon effect in vivo. 3.
      When administered in the mesenteric vein, pancreastatin inhibited the increase in
      insulin levels induced by glucagon stimulation, thereby potentiating the
      hyperglycemic effect of glucagon. 4. This study describes a regulatory role of
      pancreastatin on glucagon-induced insulin release in vivo.

PMID- 1397970
TI  - Cefaclor concentrations in human serum, gingiva, mandibular bone, and dental
      follicle following a single oral administration.
AB  - 1. Cefaclor concentrations in human serum (n = 59), gingiva (n = 46), mandibular
      bone (n = 39), and dental follicle (n = 42) following a single oral
      administration of cefaclor (500 mg) were measured by the paper disk method. 2.
      The peak times of serum, gingiva, mandibular bone, and dental follicle were 1.5,
      2, 2, and 1.5 hr, respectively. 3. The mean peak concentrations of serum,
      gingiva, mandibular bone, and dental follicle were 7.58 micrograms/ml, 3.71, 1.59
      and 2.42 micrograms/g, respectively. 4. The concentration ratios of
      gingiva/serum, mandibular bone/serum, and dental follicle/serum at peak times of
      the tissues were 0.49, 0.18, and 0.32, respectively. 5. Mean cefaclor
      concentrations in gingiva, mandibular bone, and dental follicle at peak times
      exceeded MIC for 90% for clinically isolated strains of alpha-hemolytic
      Streptococci.

PMID- 1397971
TI  - Effects of antiandrogens and progesterone on isolated rat uterus.
AB  - 1. The effect of progesterone (P, 6 x 10(-6)-6 x 10(-5) M) and the antiandrogens
      cyproterone acetate (CPA, 10(-7)-10(-5) M), flutamide (F, 10(-6)-6 x 10(-5) M)
      and spironolactone (S, 10(-6)-6 x 10(-5) M) on the KCl-induced tonic contraction
      of the isolated rat uterus have been assayed. 2. The antiandrogens relaxed, in a
      dose-dependent way, the KCl-induced contraction (EC50, 2.804 +/- 0.506 x 10(-6);
      1.671 +/- 0.308 x 10(-5); and 3.042 +/- 0.14 x 10(-5) M, respectively for CPA, S
      and F). P also relaxed the KCl-induced contraction (EC50, 2.436 +/- 0.524 x 10(
      5) M). 3. CaCl2 (0.1-10 mM) counteracted the relaxing effect of CPA, S, F, and P,
      respectively, up to 100, 80.63, 60.66 and 90.57%. 4. The 17-OH-progesterone
      derivative CPA, but not S or F, reduces at small doses (6 x 10(-8) M), but not at
      higher concentrations (6 x 10(-7)-6 x 10(-6) M), the relaxing effect of
      progesterone.

PMID- 1397972
TI  - Antimuscarinic activity of telenzepine on isolated human urinary bladder: no role
      for M1-muscarinic receptors.
AB  - 1. The antimuscarinic activity of the selective M1-blocking drug, telenzepine,
      was investigated on the isolated human urinary bladder, contracted with exogenous
      muscarinic agonists and with field stimulation. 2. Telenzepine (3 x 10(-8)-10(-5)
      M) concentration-dependently shifted to the right the dose-response curves of
      bethanechol, acetylcholine and McN-A343, and partially depressed the electrically
      evoked twitch responses. 3. pA2 values of telenzepine against bethanechol and McN
      A343 were very close. 4. McN-A343 did not modify twitch responses elicited by
      field stimulation up to 10(-5) M. 5. The lack of muscarinic M1 receptors in human
      detrusor muscle is confirmed.

PMID- 1397973
TI  - Porphyrinogenic properties of the anesthetic enflurane.
AB  - 1. The effect of enflurane, a volatile anesthetic, on heme metabolism was
      studied. Different doses (0.5-6.0 ml/kg) of this anesthetic were administered
      i.p. to mice and animals sacrificed at different times after administration (5
      240 min). 2. The dose of 2 ml/kg was chosen as the optimum anesthetic dose
      producing more alterations in the heme pathway. 3. ALA-S was significantly
      induced at earlier times of anesthesia. 4. Blood PBGase and deaminase was greatly
      reduced. 5. This diminution coupled with ALA-S induction are in accordance with
      the known biochemical changes occurring in acute intermittent porphyria and
      include enflurane in the list of porphyrinogenic drugs, the use of which is not
      recommended for the management of anesthesia in porphyric patients.

PMID- 1397974
TI  - Differential effects of hypothermia upon blood acid-base state and blood gases in
      sodium pentobarbital and urethane anaesthetised rats.
AB  - 1. The effects of two anaesthetics, sodium pentobarbital and urethane, and the
      effects of anaesthesia-associated hypothermia on acid-base status and blood gases
      were studied in rats without assisted ventilation. 2. Manipulation of conscious
      rats produces a progressive increase in arterial lactate associated with slight
      hyperventilation. 3. Sodium pentobarbital anaesthesia produces mild respiratory
      acidosis accompanied by increase in lactate arterial values. Urethane anaesthesia
      leads to partially compensated metabolic acidosis. 4. Hypothermia reduces
      metabolic acidosis and hypercapnia induced by sodium pentobarbital anaesthesia.
      No difference between hypothermic and normothermic values was observed in
      urethane anaesthesia.

PMID- 1397975
TI  - Selected biological activities of novel selenonium choline analogs.
AB  - 1. The novel choline analogs selenonium choline (SeCh) and acetylselenonium
      choline (ASeCh) have been examined for selected biological activities. 2. ASeCh
      was found to be an alternative substrate for acetylcholine esterase with Km and
      Vmax values similar to acetylcholine. 3. ASeCh and SeCh inhibited
      acetylthiocholine hydrolysis by acetylcholinesterase with IC50 values similar to
      acetylcholine and choline. 4. SeCh exerted a protective action against
      physostigmine and DFP induced toxicity. 5. SeCh (85 mg/kg) was found to be 3
      times more toxic in mice than choline.

PMID- 1397976
TI  - Estrogen binding sites in peripheral blood monocytes and effects of danazol on
      their sites in vitro.
AB  - 1. This study was designed to investigate the presence of estrogen type I (high
      affinity, low capacity) and type II (low affinity, high capacity) binding sites
      in human peripheral blood monocytes and the effects of danazol on these sites. 2.
      These two types of estrogen binding sites existed in human peripheral blood
      monocytes. 3. Danazol bound to these sites in high concentration (10(-6) M,
      clinical serum concentration during danazol therapy) and decreased the number of
      both sites. 4. It is suggested that danazol has an anti-estrogenic action to the
      monocytes through the competition and suppression of estrogen binding sites as
      seen in the estrogen target organ.

PMID- 1397977
TI  - Isolation of sesbanimide from the seed of Sesbania vesicaria.
AB  - 1. The HPLC separation of a water-soluble toxic fraction isolated from the seed
      of Sesbania vesicaria provided a potent antileukemic compound which was
      identified as sesbanimide (or sesbanimide A). The identity was established by
      comparison of the proton magnetic resonance spectra of the isolated sesbanimide
      and the authentic sample. 2. The IC50 value determined by the activity against
      the growth of murine leukemia (L1210) cells in vitro was 0.8 ng/ml.

PMID- 1397978
TI  - Biphasic effect of histamine on spontaneously beating rat atria.
AB  - 1. Effect of histamine (HA) (10(-4)-10(-2) M) on spontaneously beating rat atrium
      was investigated. HA produced a biphasic effect which is composed of an initial
      negative chronotropy followed by a positive chronotropic phase, at each single
      dose. 2. At a submaximal dose of HA (3 x 10(-3) M) we have investigated the
      effects of some antagonists on the biphasic effect profile. 3. Propranolol (10(
      7) M) depressed the secondary phase by abolishing the biphasic pattern of the
      effect of HA leading it to a monophasic one (negative chronotropy). 4. On the
      other hand, combination with atropine (10(-7) M) was shown to reduce the negative
      inotropic effect (in the secondary phase) which was produced by HA in the
      presence of propranolol. 5. The initial negative chronotropic phase was
      significantly enhanced by propranolol and reduced by pheniramine (10(-6) M). 6.
      Pheniramine also potentiated the positive chronotropy at the secondary phase of
      the response, but cimetidine (10(-4) M) has no significant effect on both phases.
      7. Theophylline (10(-4) M) abolished the initial negative chronotropic phase, but
      did not influence the secondary phase. Dipyridamole (10(-5) M) did not affect the
      secondary phase of the response of HA, but increased the initial negative
      chronotropic effect.

PMID- 1397980
TI  - Effects of oxazolidines derived from (-) ephedrine in the rat.
AB  - 1. Five oxazolidines were synthesized by reaction of (-) ephedrine with aliphatic
      aldehydes. The aldehydes used were formaldehyde, propionaldehyde, butyraldehyde,
      isobutyraldehyde and trimethylacetaldehye. 2. These five oxazolidines were tested
      in rats for ephedrine-like pharmacological activity using the hyperthermia and
      anorexia models. 3. All five oxazolidines caused significant elevation of body
      temperature in the hyperthermia model. The oxazolidine synthesized from (-)
      ephedrine and butyraldehyde caused greatest hyperthermia. 4. Four oxazolidines
      caused significant anorectic responses. The oxazolidine synthesized from (-)
      ephedrine and isobutyraldehyde caused greatest anorexia. 5. A possible tolerance
      to the anorectic effects of some of the compounds was observed.

PMID- 1397979
TI  - Enhancement of gastric mucosal epidermal growth factor and platelet-derived
      growth factor receptor expression by sucralfate.
AB  - 1. The effect of an anti-ulcer agent, sucralfate, on the expression of gastric
      mucosal epidermal growth factor (EGF) and platelet derived growth factor (PDGF)
      receptors was investigated. 2. Gastric mucosal cell membranes, isolated from the
      stomach of groups of rats, one receiving twice daily for 3 consecutive days a
      dose of 100 mg/kg sucralfate, and the other only the vehicle, were used as source
      for EGF and PDGF receptors. 3. Binding assays revealed the presence of both types
      of receptors, activation of which led to the elevation of tyrosine kinase
      activity as evidenced by a marked increase in membrane protein tyrosine
      phosphorylation patterns. 4. The specific receptor binding in the control group
      was 2.46 fmol/mg protein for EGF and 1.46 fmol/mg protein for PDGF, whereas the
      respective binding values in the sucralfate treated group increased by 61 and
      65%. 5. The results suggest that sucralfate is capable of enhancement of
      epithelial proliferative activities through the stimulation of gastric mucosal
      EGF and PDGF receptors.

PMID- 1397982
TI  - Dexamethasone modifies morphine-, atropine-, verapamil-induced constipation in
      mice.
AB  - 1. The effect of dexamethasone in gastrointestinal constipation induced by
      morphine, verapamil and atropine in mice has been studied. 2. These drugs caused
      a dose-related inhibition of charcoal meal transit, which was reversed by
      dexamethasone. 3. Dexamethasone resulted more active in reversing morphine and
      atropine constipation, than in modifying verapamil effect. 4. The authors
      concluded that the interaction of dexamethasone on its receptor could release a
      larger amount of acetylcholine resulting in a reversion of atropine- or morphine
      induced constipation. 5. The minor effect of dexamethasone on verapamil-induced
      constipation suggest a reduced involvement of calcium influx. 6. The above
      results suggest a role for steroid in gastrointestinal transit and propose a
      possible mechanism through which dexamethasone could reverse morphine- and
      atropine-induced constipation.

PMID- 1397981
TI  - Calcium ion itself inhibits Ca-free contraction of various smooth muscles in
      response to adrenergic and cholinergic stimulations and to TPA in the absence of
      Ca channel blocker and EGTA.
AB  - 1. Smooth muscles such as thoracic aorta, stomach and vas deferens contract
      tonically in the absence of Ca ion (Ca) in response to various agonists such as
      norepinephrine, carbachol and TPA. 2. Addition of Ca alone to the Ca-free medium
      relaxes the muscle that has been contracting in response to the agonist in the Ca
      free medium. 3. Ca itself has an inhibitory action on the contraction. 4.
      Acidification of the medium relaxes the muscle as Ca does, but weakly.

PMID- 1397983
TI  - One- and two-electron reduction of menadione in guinea-pig and rat cardiac
      tissue.
AB  - 1. In both guinea-pig and rat heart, mitochondrial NADH-ubiquinone-reductase and
      soluble DT-diaphorase accounted for 49-50% and 48-50% of menadione metabolism,
      respectively. Microsomal NADPH-cytochrome P450-reductase was responsible for less
      than 1% of menadione reduction. 2. Menadione was a high-affinity substrate for
      all reductases (Km values from 1 to 10 microM). 3. Marked amounts of O2-.
      (superoxide anion) were generated as a consequence of cardiac metabolism of
      menadione. 4. Menadione-induced O2-. generation was about 3-fold higher in guinea
      pig than in rat heart. 5. All results were compared with data obtained on guinea
      pig and rat liver.

PMID- 1397984
TI  - Effect of lithium on gastro-intestinal complications in alloxan-diabetic rats.
AB  - 1. Decreased beta-adrenergic and serotonergic responses have been reported in
      gastro-intestinal tract of experimentally diabetic rats. Effects of lithium on
      the decreased beta-adrenergic and serotonergic responsiveness of the gastro
      intestinal tract due to diabetes were investigated using gastric fundus strips
      and proximal duodenum from alloxan diabetic rats. 2. A 6-day treatment with
      lithium chloride (2 mEq/kg i.p. in saline) normalized the decreased gastro
      intestinal responses of the alloxan-diabetic rats, whereas the lithium treatment
      did not affect the elevated blood glucose levels due to experimental diabetes. 3.
      Furthermore, the lithium treatments of control and alloxan-diabetic rats did not
      alter the relaxing effect of manganese chloride on the isolated duodenum. 4.
      These results strongly suggest that the improving effect of lithium is not
      related to adenylate cyclase activation and may be as a consequence of its direct
      action on the diabetic gastro-intestinal smooth muscles.

PMID- 1397985
TI  - Vasomotor responses in the isolated perfused external and internal carotid
      vascular beds of the rat.
AB  - 1. The external (ECB) or the internal (ICB) carotid vascular beds of the rat were
      isolated and perfused with Krebs-Henseleit solution at constant flow (1 ml/min).
      Changes in perfusion pressure (PP) were recorded after cervical sympathetic
      stimulation and after the administration of norepinephrine (NE) and serotonin (5
      HT). 2. Sympathetic stimulation induced an increase in PP (vasoconstriction) in
      both vascular beds, however, this effect was significantly higher in the ECB than
      in the ICB. 3. Exogenous NE also induced a significantly higher contractile
      response in the ECB. 4. Prazosin (10(-8) M) significantly inhibited the response
      to sympathetic stimulation and to NE both in the ECB and in the ICB, but
      yohimbine (10(-7) M) had no effect, suggesting that the vasoconstriction was
      mainly due to the activation of alpha 1-adrenoceptors. 5. 5-HT induced a
      contractile response both in the ECB and the ICB. In contrast with the response
      to NE, the contraction induced by 5-HT in the ICB was significantly higher than
      in the ECB. 6. Ketanserine (10(-8) M) antagonised both responses, indicating the
      involvement of 5-HT2 receptors. 7. The contractile effect of 5-HT in the ECB was
      significantly enhanced by a subthreshold sympathetic stimulation that did not
      modify the PP by itself. This effect was not seen in the ICB. 8. The differential
      perfusions of the ECB or the ICB demonstrated a different reactivity of ECB and
      ICB, both to sympathetic stimulation and to the administration of exogenous NE or
      5-HT. 9. Furthermore, the response to 5-HT in the ECB was modulated by a
      subthreshold sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1397986
TI  - Effect of methyl methacrylate on isolated atria and interaction with
      isoproterenol, atropine and calcium chloride.
AB  - 1. Spontaneous rate and contractile force of isolated rat and rabbit atria
      suspended in a tissue bath were recorded before and after drugs. Methyl
      methacrylate monomer (MMA) alone both decreased force and increased rate dose
      dependently. 2. Concentrations of calcium chloride or isoproterenol that alone
      increased both rate and force of rat atrial contraction were fully and only
      partially able, respectively, to restore force to normal after MMA. 3. Atropine
      prevented changes in rat atrial function from low-effective doses of MMA, but not
      higher ones; it also failed to prevent the reduction of contractile force by a
      calcium channel blocker, verapamil. 4. There are similarities but also
      differences between actions of MMA and verapamil on rat atria.

PMID- 1397988
TI  - A challenge to doctor-patient confidentiality: when HIV-positive patients refuse
      disclosure to spouses.

PMID- 1397987
TI  - Footshock stress-induced supersensitivity to isoprenaline in the isolated
      pacemaker of the rat: effects of the compounds RU-38486 and RU-28362.
AB  - 1. Three daily sessions of inescapable footshock stress of 30 min duration each
      increased the sensitivity of the isolated pacemaker of the rat to the
      chronotropic effect of isoprenaline. 2. The effect of inescapable footshock
      stress on the sensitivity of the isolated rat pacemaker to the chronotropic
      effect of isoprenaline was prevented by the daily administration of the compound
      RU-38486, a potent antiglucocorticoid which blocks the cytosolic receptor for
      corticosterone. 3. The administration of the compound RU-28362, a potent agonist
      of the cytosolic receptor for corticosterone, during 3 days to rats which were
      not submitted to footshock stress induces supersensitivity to the chronotropic
      effect of isoprenaline. 4. It is concluded that corticosterone plays an important
      role in the qualitative control of the rat pacemaker beta-adrenoceptor population
      during adaptation to repeated footshock stress.

PMID- 1397989
TI  - Drugs approved by the FDA in 1991.

PMID- 1397990
TI  - A review of local anesthetics.

PMID- 1397991
TI  - Route of entry of vapors into anesthetic cartridges.

PMID- 1397992
TI  - Corticosteroid therapy in general dental practice.

PMID- 1397993
TI  - Management of dens evaginatus.

PMID- 1397995
TI  - Dental management of a patient with aplastic anemia.

PMID- 1397994
TI  - Dental management of patients who receive chemo- and radiation therapy.

PMID- 1397996
TI  - Transitional dentures: a better immediate prosthesis leads to successful
      restoration.

PMID- 1397997
TI  - Subcutaneous emphysema in dental practice.

PMID- 1397998
TI  - State radiation safety laws and the dental office.

PMID- 1397999
TI  - The effects of daily injections of L-dihydroxyphenylalanine and 5
      hydroxytryptophan in different temporal relationships on thyroid-gonadal
      interaction in an Indian finch, spotted munia, Lonchura punctulata.
AB  - Daily injection of L-dihydroxyphenylalanine (L-DOPA, a dopamine precursor) given
      12 hr after 5-hydroxytryptophan (5-HTP, a serotonin precursor) stimulated
      testicular growth and body weight increase in the spotted munia Lonchura
      punctulata. Daily injections of the same drugs given 8 hr apart had the opposite
      effect, inhibiting both testicular growth and body weight gain. These responses
      were not observed when either of the drugs were given alone, indicating that the
      effect was due to temporal synergism between serotonergic and dopaminergic
      functions. The inhibitory effect of daily injections of thyroxine on testicular
      and body growth were negated by injections of 5-HTP and L-DOPA separated by 12
      hr. Conversely, the stimulatory effects of thyroidectomy in maintaining full
      testicular size and body weight after the breeding seasons were negated by daily
      injections of 5-HTP and L-DOPA separated by 8 hr. It is concluded that the
      inverse relationship between seasonal changes in thyroidal and reproductive
      functions may involve seasonal changes in phase relationships between daily
      rhythm in serotonergic and dopaminergic activity in the central nervous system.

PMID- 1398000
TI  - Effects of fasting, medium glucose, and amino acid concentrations on prolactin
      and growth hormone release, in vitro, from the pituitary of the tilapia
      Oreochromis mossambicus.
AB  - Previous investigations have shown that the release of PRL and GH from the
      tilapia pituitary is directly sensitive to osmotic pressure and a variety of
      endocrine and neuroendocrine factors. The present studies were aimed at
      determining whether the spontaneous release of PRL and GH, in vitro, is: (1)
      sensitive to the nutritional status of the fish, and (2) responsive to variations
      in the D-glucose and total amino acid content of the incubation medium. In the
      first series of experiments, male fish (50 to 60 g) were divided into two groups.
      One group was fed twice daily for 2 weeks while the second received no food. A
      nearly homogeneous mass of PRL-secreting cells was dissected from the rostral
      pars distalis (RPD) and incubated for 18 to 20 hr in either hyposmotic (300
      mOsmolal) or hyperosmotic (355 mOsmolal) medium. Similarly, a mass of GH
      secreting cells was dissected from the proximal pars distalis (PPD) and incubated
      for 18 to 20 hr in isosmotic (320 mOsmolal) medium. Fasting was found to alter
      the total amount of PRL and GH in the culture well (tissue + medium) at the end
      of the incubations, decreasing PRL and increasing GH. Fasting was also found to
      both reduce spontaneous PRL release in vitro and suppress its stimulation by
      reduced osmotic pressure (P less than 0.01). By contrast, fasting resulted in a
      substantial increase in spontaneous GH release from the PPD in vitro (P less than
      0.01). In the second series of experiments, GH release was found to increase as
      the D-glucose concentration of the medium decreased (P less than 0.01), while
      prolactin release was unresponsive.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398001
TI  - In vitro induction of vitellogenin synthesis in Rana esculenta: role of the
      pituitary.
AB  - Vitellogenin (VTG), a complex protein, is a precursor of yolk protein
      (lipovitellin and phosvitin) in all oviparous vertebrates studied to date. In
      amphibians, as in other oviparous vertebrates, VTG synthesis is hormonally
      dependent; estradiol-17 beta (E2) is especially important, although in vivo in
      the frog Rana esculenta the pituitary may be involved in hepatic VTG synthesis
      and secretion. The present in vitro experiments carried out during the main
      phases of the annual reproductive cycle of this frog showed that homologous
      pituitary homogenate (HPH), as well as E2, stimulated VTG synthesis in male and
      female livers, although their patterns of VTG secretion showed some differences
      with respect to the induction time and the rate of VTG secretion. The hepatic
      response to HPH occurred after a longer time than that of E2 VTG induction, and
      no cooperation between HPH and E2 was found in the VTG synthesizing response. It
      should be emphasized that during the refractory period (July), hepatic VTG
      synthesis in males and females could only be induced by HPH. These data
      demonstrate, for the first time, a direct action of HPH on VTG synthesis in male
      and female frog livers in all the periods tested; hepatic responsiveness to HPH
      and E2 varies with season and sex.

PMID- 1398002
TI  - Steroid metabolism by ovarian follicles and extrafollicular tissue of the guppy
      (Poecilia reticulata) during oocyte growth and gestation.
AB  - In the viviparous guppy, fertilization and gestation are intrafollicular. Fully
      developed embryos are ovulated at the end of gestation just prior to parturition.
      The metabolism in vitro of various radiolabeled steroid precursors by isolated
      ovarian follicles at various stages of the reproductive cycle and extrafollicular
      (EF) tissue of the guppy was investigated. While estradiol-17 beta was one of the
      end products of metabolism in vitellogenic follicles, 17 alpha, 20 beta-P and
      several 5-reduced metabolites were synthesized by postvitellogenic follicles. The
      yield of 17 alpha, 20 beta-P, however, was much lower than some 5 beta-reduced
      metabolites synthesized by postvitellogenic follicles. Gestation stage follicles
      rapidly converted the precursors into 5-reduced and polar 7-hydroxylated
      steroids, and their glucuronides. Although postpartum follicles showed very poor
      potential for steroid metabolism, they synthesized estradiol-17 beta from
      testosterone. These results demonstrate distinct changes occurring in the
      steroidogenic potential of the follicles during the reproductive cycle. Unlike in
      other viviparous vertebrates, no particular steroid seems to be involved in
      maintaining gestation in the guppy; all the steroid precursors are converted into
      highly polar metabolites and their conjugates during gestation, thereby
      facilitating their excretion. The EF ovarian tissue also synthesized 7
      hydroxylated steroids and their glucuronides, providing evidence for the first
      time that the teleost ovarian EF tissue plays a role in steroidogenesis. The
      possible physiological significance of the synthesis of the novel polar steroids
      by the follicles and the EF tissue is discussed.

PMID- 1398003
TI  - Parathyroid and ultimobranchial glands of the estuarine snake, Cerberus rhynchops
      (Schneider).

PMID- 1398004
TI  - Stimulation of coho salmon growth by insulin-like growth factor I.
AB  - The effect of insulin-like growth factor I on growth rate of coho salmon
      (Oncorhynchus kisutch) was examined. Juvenile coho salmon received implants of
      osmotic minipumps containing recombinant bovine insulin-like growth factor I
      (rbIGF-I) or saline for a period of 3 to 4 weeks. High doses of rbIGF-I (greater
      than 0.13 microgram.g-1.d-1) resulted in hypoglycemia and death. In 2-year-old
      coho salmon, 0.09 microgram.g-1.d-1 rbIGF-I administered for 25 days doubled
      linear growth rate and increased growth rate in weight by 40%. In rapidly
      growing, 1-year-old coho salmon, growth rate was not altered by rbIGF-I at 0.01
      or 0.05 micrograms.g-1.d-1 for 31 days. In ration-limited fish exhibiting slow
      growth in the control group, rbIGF-I (0.02 microgram.g-1.d-1) increased linear
      growth rate by up to threefold and growth rate in weight by up to fourfold. The
      results indicate that exogenous treatment with mammalian IGF-I can stimulate coho
      salmon growth under some conditions, and that endogenous IGF-I may be an
      important factor in regulating growth of teleosts.

PMID- 1398005
TI  - Neuropeptide Y-like immunoreactivity in the dogfish gastroenteropancreatic tract:
      light and electron microscopical study.
AB  - The 36 amino acid neuropeptide Y (NPY) has been examined in mammals and is mainly
      located in the nerves. Its distribution in nonmammalian vertebrate and in some
      invertebrate nervous systems has been confirmed. Using antisera raised to porcine
      NPY, NPY immunoreactivity has been localized in endocrine cells of the pancreas
      and gastrointestinal tract of two dogfish, Scyliorhinus stellaris and
      Scyliorhinus canicula. Immunostained serial sections and cross-absorption
      experiments with related peptides, including avian and bovine pancreatic
      polypeptide and peptide tyrosine tyrosine, excluded any cross-reactivity. The
      fine structure of the cells containing NPY-like substance is described.

PMID- 1398006
TI  - Regulation of calbindin D 28K and its mRNA in the intestine of the domestic hen.
AB  - Intestinal calbindin synthesis in laying hens was analyzed to assess controlling
      factors operating during egg formation. In the absence of vitamin D, calbindin
      was not induced by estrogen and testosterone. In immature vitamin D-replete
      pullet, blood levels of 1,25(OH)2D3 increased in response to estrogen but the
      duodenal concentration of calbindin and its mRNA were increased only when
      testosterone was given together with estrogen. The plasma concentration of
      1,25(OH)2D3 and the duodenal levels of calbindin and its mRNA were substantially
      higher in laying hens than in immature pullets. No differences in these
      parameters were observed between the stages of the ovulatory cycle. Suppression
      of shell formation for a week decreased the concentration of 1,25(OH)2D3 and of
      duodenal calbindin but did not affect the level of its mRNA. When egg shell
      formation resumed in hens previously laying shell-less eggs, the concentrations
      of 1,25(OH)2D3 and of calbindin and its mRNA increased toward the end of shell
      formation. A most important factor regulating intestinal calbindin synthesis in
      laying hens turned out to be 1,25(OH)2D3. Intestinal calbindin mRNA is more
      stable in laying hens than in young birds as its concentration declines more
      slowly when the stimulation provided by 1,25(OH)2D3 is withdrawn, as occurs
      following suppression of shell formation and after parathyroidectomy in laying
      birds. Intestinal calbindin mRNA is therefore increased by a process other than
      increasing 1,25(OH)2D3 formation. The factor influencing the stability of this
      mRNA in laying hens could be calcium. It is concluded that in hens the increased
      duodenal calbindin synthesis elicited by plasma 1,25(OH)2D3 at sexual maturity
      primarily involves a transcriptional process and the stabilization of the
      mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398007
TI  - Characterization of a sustained-release estrogen implant on oviduct development
      and plasma Ca concentrations in broiler breeder chicks: modulation by feed
      restriction and thyroid state.
AB  - The effect of estradiol-17 beta (E2) given as a sustained-release implant
      (Compudose 200) on concentrations of plasma calcium (Ca) and the development of
      the chick shell gland has been investigated in food-restricted and thyroid
      hormone-treated 6- to 8-week-old broiler breeder pullets. Chicks implanted with
      0, 0.5, 1.0, 1.5, 2.0, and 3.0 Compudose pellets for 24 days (n = 6/group)
      revealed a dose-response relationship between plasma E2 and Ca and on oviduct
      growth. Plasma E2 concentrations were characterized by an initial burst phase for
      approximately 17 days, followed by a constant release phase. Histologic
      examination of shell gland tissue confirmed the dose related E2-induced
      development of microvilliated epithelium and tubular glands over time. Feed
      restriction initiated at 2 weeks of age markedly increased the response to the E2
      implants. Birds (n = 8/group) implanted with 2 pellets and feed restricted had
      increased plasma concentrations of E2 and Ca, and increased growth of the oviduct
      (P less than 0.01) as compared to ad libitum implanted birds. In a separate study
      birds (n = 6/group) had restricted access to feed from 8 weeks of age and were
      implanted with 0, 2, 4, or 8 pellets. At intervals from 9 to 45 days after
      implantation one bird from each group was killed. Although concentrations of
      plasma Ca were significantly greater in feed-restricted birds (P less than 0.01),
      oviduct growth was only marginally increased by the food restriction program.
      Plasma Ca concentrations in broiler breeder pullets (n = 8/group) implanted with
      1 or 3 pellets and injected with T3/T4 (100 micrograms/day) were significantly
      decreased (P less than 0.05). Injection of thyroid hormone also marginally
      decreased shell gland epithelial cell height (P less than 0.05) and development
      of microvilli (P less than 0.05). There was no effect of the administration of
      the goitrogen, propylthiouracil (10 micrograms/day im), on the E2 induced
      development of the shell gland.

PMID- 1398008
TI  - A reduction in pituitary dopamine turnover is associated with sex pheromone
      induced gonadotropin secretion in male goldfish.
AB  - In goldfish, the gonadal steroid, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one
      (17,20 beta-P), functions as a potent preovulatory female sex pheromone which
      stimulates rapid elevations in serum gonadotropin (GtH) levels and subsequent
      increases in milt production in males. GtH secretion in goldfish is known to be
      regulated by the stimulatory actions of gonadotropin-releasing hormone (GnRH) and
      the inhibitory actions of dopamine (DA). This study specifically examined whether
      the 17,20 beta-P-induced elevation in male GtH is caused by pheromone-mediated
      changes in DA inhibition at the level of the pituitary. First, we have
      demonstrated that dihydroxyphenylacetic acid (DOPAC) is the primary metabolite of
      DA catabolism in the brain and pituitary gland of goldfish. Second, we measured
      changes in circulating levels of GtH and changes in pituitary content of DA and
      its metabolite, DOPAC, as well as possible alterations in DA turnover rate
      (DOPAC/DA ratio) following short-term exposure of male goldfish to water-borne
      17,20 beta-P. Water-borne 17,20 beta-P consistently increased serum GtH levels in
      males within 20 min of exposure and maintained elevated levels for up to 120 min.
      Although changes in pituitary DA content were not observed during periods of high
      GtH release, coincident reductions in pituitary levels of DOPAC were measured
      within 45 min of exposure to the pheromone. More importantly, there was a
      significant decrease in the rate of DA turnover in the pituitary, as assessed by
      comparing the ratio of DOPAC to DA present, at 20, 45, and 120 min of exposure.
      Since the reduction of DA turnover in the pituitary is inversely correlated with
      periods of increased GtH release, the present results suggest that water-borne
      17,20 beta-P causes an abatement of DA release to the pituitary. Based on the
      latency of the GtH response to water-borne 17,20 beta-P, a rapid reduction of DA
      turnover in the pituitary appears to be at least part of the neuroendocrine
      trigger for 17,20 beta-P-induced GtH release in male goldfish.

PMID- 1398009
TI  - Structure-cardiovascular activity relationships of parathyroid hormone.
AB  - The effects of parathyroid hormone (PTH) analogues on isolated rat tail arteries
      and frog arteries and heart were examined. Synthetic bovine PTH fragment 1 to 34
      [bPTH-(1-34)], porcine PTH-(1-34), [Ala1] pPTH-(1-34), and [Nle8] pPTH-(1-34)
      were tested for vasorelaxant activity on helical strips of the rat tail artery
      and the frog iliac and femoral artery, preconstricted with arginine vasopressin
      or arginine vasotocin in the rat and the frog, respectively. For cardiac
      activity, PTH analogues were administered to isolated frog atria, and atrial rate
      and atrial tension (AT) were measured. The N-terminal amino acid alanine appears
      to be pivotal for vasorelaxant activity of PTH molecules on the rat tail artery
      strips. Data from the frog preparations supported the finding in the rat,
      although the iliac and femoral arterial preparations differed in their responses.
      The N-terminal serine in pPTH-(1-34), compared with the other PTH analogues,
      appeared to be responsible for different cardiac responses, being negatively
      chronotropic and without effect on AT.

PMID- 1398010
TI  - A possible involvement of prostaglandin F2 alpha (PGF2 alpha) in Rana esculenta
      ovulation: effects of mammalian gonadotropin-releasing hormone on in vitro PGF2
      alpha and 17 beta-estradiol production from ovary and oviduct.
AB  - The present work studied the PGF2 alpha and 17 beta-estradiol plasma levels
      during ovulation, and the in vitro effects of mammalian gonadotropin-releasing
      hormone (mGnRH) on ovarian and oviductal production of prostaglandin F2 alpha
      (PGF2 alpha) and 17 beta-estradiol during four different stages of the annual
      sexual cycle in water frog, Rana esculenta. Plasma levels of PGF2 alpha increased
      in ovulating frogs, with respect to preovulatory and postovulatory levels, while
      estradiol did not change. In addition, mGnRH increased PGF2 alpha and 17 beta
      estradiol in the incubation media of ovaries taken during the recovery stage.
      Moreover, mGnRH increased PGF2 alpha in incubation media of oviducts collected
      during the reproductive stage. These findings suggest that PGF2 alpha could be
      involved in the control of egg deposition in the female R.

PMID- 1398011
TI  - Plasma progesterone levels in the pregnant female rat-kangaroo (Bettongia
      gaimardi).
AB  - Plasma progesterone levels were measured in female bettongs (small macropodid
      marsupials) under two natural regimes: (1) during "delayed" gestation (initiated
      by removal of pouch young, RPY) and (2) during the pregnancy prior to pouch
      vacation when a young still occupies the pouch (i.e., during lactation). Basal
      levels of progesterone were 0.15-0.5 ng/ml. There was a transient peak of
      progesterone (0.7 ng/ml) early in gestation at Day 4 RPY. After Day 6 RPY,
      progesterone levels remained elevated (1.2-1.5 ng/ml) until they dropped sharply
      to basal levels on the day of birth. This pattern of progesterone secretion
      during delayed gestation is similar to that seen in other marsupials, such as the
      tammar wallaby. There was no significant difference between the progesterone
      profiles of the two experimental groups. We deduce, then, that lactation had no
      effect on corpus luteum function (as assessed by plasma progesterone levels) in
      the pregnant bettong.

PMID- 1398012
TI  - Lack of effect of TRH on alpha-MSH release from the neurointermediate lobe of the
      lizard Lacerta vivipara.
AB  - Thyrotropin-releasing hormone (TRH) is a potent stimulator of melanotropin (alpha
      MSH) release from pituitary melanotrophs in pig, frog, and fish. Concurrently, it
      has recently been shown that injection of TRH induces skin darkening in the
      lizard Anolis carolinensis (Licht and Denver, 1988). In the present study, we
      have thus investigated in vitro the possible effect of TRH on alpha-MSH release
      from the lizard (Lacerta vivipara) neurointermediate lobe, by means of the
      perifusion technique. Using our radioimmunoassay procedure, we found that serial
      dilutions of L. vivipara NIL extracts and synthetic alpha-MSH gave parallel
      binding curves. Administration of graded doses of TRH (10(-8)-10(-6) M) did not
      cause any modification of alpha-MSH release. In contrast, infusion of a
      depolarizing concentration of K+ induced a robust stimulation of alpha-MSH
      secretion. These results indicate that, in the lizard L. vivipara, the
      neuropeptide TRH does not stimulate pituitary melanotrophs.

PMID- 1398013
TI  - In vitro effects of homologous prolactins on testosterone production by testes of
      tilapia (Oreochromis mossambicus).
AB  - The tilapia, Oreochromis mossambicus, produces two prolactins designated tPRL177
      and tPRL188 to indicate the number of amino acid residues in each. The direct in
      vitro actions of tPRL177 and tPRL188 on basal and ovine luteinizing hormone (LH)
      induced testosterone production in minced testes of courting and noncourting
      (bachelor) tilapia were examined. Courting males were housed with females and
      were used as soon as they built a spawning pit; noncourting males were housed
      with other males and were used when they appeared female-like in coloration. The
      in vitro culture system consisted of two phases. In phase 1 (0-10 hr), testicular
      tissue was incubated without (control) or with the tPRLs--both alone and together
      and in doses ranging from 0.5 to 32 microM. In phase 2 (10-16 hr), the culture
      medium was replaced with medium containing 6.25 microM (0.25 micrograms/ml) ovine
      LH. Testosterone production during both phases was determined by radioimmunoassay
      of the medium. The tPRLs stimulated testosterone production during phase 1 in
      courting males (by 25%) but not in noncourting males. Exposure to either or both
      tPRLs in phase 1 enhanced the response of testicular tissue from courting males
      to ovine LH (by 10%) and inhibited the response of minced testes taken from
      noncourting males (by 12%). This is the first evidence to demonstrate direct
      gonadal activity of homologous PRL in a teleost.

PMID- 1398014
TI  - Inhibition of protein kinase C antagonizes in vitro tadpole tail fin regression
      induced by thyroxine.
AB  - Tail fin regression can be induced in anuran amphibians with L-thyroxine (T4).
      This regression can be antagonized with prolactin (PRL). Previous work had
      suggested that protein kinase C (PKC) was involved in PRL action. To address this
      issue further, the effect of a potent and selective inhibitor of protein kinase C
      on in vitro tail fin regression was investigated. T4-induced regression of tail
      fin pieces from Rana pipiens tadpoles could be antagonized by adding PRL or the
      PKC inhibitor H-7 to the medium. H-7 inhibited fin regression in a dose-dependent
      manner, with a half-maximal effective concentration of about 10(-5) M. The H-7
      analogue, HA-1004 (which is not a selective inhibitor of PKC), was without
      effect. These results suggest a possible role for PKC in tail fin regression and
      may be useful in elucidating the antimetamorphic action of PRL.

PMID- 1398015
TI  - Effects of nutritional state, insulin, and glucagon on lipid mobilization in
      rainbow trout, Oncorhynchus mykiss.
AB  - The effects of nutritional state, insulin, and glucagon on lipid mobilization
      were determined in rainbow trout, Oncorhynchus mykiss. In nutritional state
      experiments, fish were either fed continuously (except 24 to 36 hr prior to
      experimentation) with commercial trout chow or fasted for 4 weeks. Lipase
      activity in liver tissue isolated from fasted fish and cultured for 5 hr was
      greater than that in tissue isolated from fed fish and cultured. The presence of
      glucose (5.55 mM) in the incubation medium accentuates lipolytic activity in both
      liver and adipose tissue. Hormone response was assessed both in vivo and in
      vitro. Salmon insulin was injected into anesthetized fish (fed continuously
      except 24 hr prior to injections) in 10 microliters of saline/g body weight;
      final hormone dose was 100 ng/g body weight. Tissue and plasma were sampled 1 and
      3 hr after injection. Insulin resulted in depressed plasma FA concentration and
      reduced hepatic triacylglycerol lipase activity. In vitro effects of hormones
      were evaluated by incubating liver and adipose tissue pieces in Hanks-MEM.
      Glucagon (bovine/porcine) directly stimulated lipid breakdown in both liver and
      adipose tissue. These actions were manifested by enhanced FA and glycerol
      released into the culture medium and by elevated triacylglycerol lipase activity.
      Insulin (bovine) generally appeared antilipolytic as this agent inhibited
      glucagon-stimulated lipase activity and glucagon-stimulated FA release.
      Furthermore, insulin (in the presence of glucose) reduced net lipolysis, as
      indicated by glycerol release, compared to control cultures. These results
      indicate that nutritional state and glucose are important modulators of lipid
      mobilization and that glucagon and insulin act directly on lipid storage sites to
      coordinate lipolysis in rainbow trout.

PMID- 1398016
TI  - Liver and brain glucocorticoid receptor in rainbow trout, Oncorhynchus mykiss:
      down-regulation by dexamethasone.
AB  - Total glucocorticoid binding sites were identified and quantitated in liver and
      brain of rainbow trout using an exchange method and [3H]dexamethasone as the
      ligand. Both tissues contained a predominantly cytosolic moiety that bound
      dexamethasone with high specificity. Binding was saturable, time dependent, and
      completely reversible. Scatchard analysis showed a linear relationship suggesting
      that receptors belong to a single class. Dexamethasone down-regulated both liver
      and brain receptors. Down-regulation was rapid (within hours) and dose dependent
      (ED50 = 1.5 mg/kg body weight). Dexamethasone-induced down-regulation was not a
      result of cytoplasm to nuclei translocation or due to increases in tissue
      concentrations of steroid. Dexamethasone administration resulted in a lowering of
      Bmax (82.3 +/- 2.5 to 20.6 +/- 10.5 fmol/mg protein) and an increase in Kd (15.6
      +/- 0.2 to 44.3 +/- 5.0 nM) suggesting a conformational change in the receptor
      molecule as part of the mechanism. The brain and liver of the rainbow trout thus
      have glucocorticoid receptors similar to those described in the mammalian system.
      Further, these receptors are subjected to autologous regulation similar to their
      counterparts in other systems.

PMID- 1398017
TI  - Plasma sex steroid binding proteins (SSBP) in the male lizard, Podarcis s.
      sicula, during the reproductive cycle.
AB  - In male Podarcis s. sicula plasma, a sex steroid binding protein [SSBP(s)] binds
      testosterone (T) and estradiol-17 beta (E2) with moderate affinity (Kd = 0.23 +/-
      0.08 x 10(-8) for 3H-E2, and 0.24 +/- 0.07 x 10(-8) for 3H-T) and high capacity.
      The SSBP binding affinity is unchanged throughout the sexual cycle, although its
      capacity is higher in nonreproductive males (winter and postreproductive period).
      This change may be related to changes in plasma T and E2 levels, and is likely to
      be involved in mechanisms whereby free steroid is delivered to target organs.
      SSBP, under isoelectrofocusing, is distributed between pH 5.5-6.5 and pH 7.1-7.5.
      The concentration of these two forms varies during the annual cycle.

PMID- 1398019
TI  - Molecular cloning of silver carp and bighead carp prolactin.
AB  - The cDNAs encoding the prolactin of silver carp (scPRL) and bighead carp (bcPRL)
      have been cloned. Deduced from the nucleotide sequences, both scPRL and bcPRL are
      composed of 187 amino acid residues. Only one residue is different between scPRL
      and bcPRL. Homology analysis indicates that scPRL and bcPRL are highly homologous
      to carp PRL (97%), relatively conserved in relation to PRLs of salmon, trout, and
      tilapia (64-69%), and diversified from avian and mammalian PRL (30-35%). Similar
      to PRLs of other species of fish, scPRL and bcPRL lack the first 12 N-terminal
      residues of avian and mammalian PRLs.

PMID- 1398018
TI  - Mammalian GnRH involvement in prostaglandin F2 alpha and sex steroid hormones
      testicular release in two amphibian species: the anuran water frog, Rana
      esculenta, and the urodele crested newt, Triturus carnifex.
AB  - The present work was carried out to study the in vitro effects of mammalian
      gonadotropin-releasing hormone (mGnRH) on Rana esculenta and Triturus carnifex
      testis production of prostaglandin F2 alpha (PGF2 alpha) and sex steroid hormones
      during the prereproduction, reproduction, and postreproduction periods. In R.
      esculenta, testicular PGF2 alpha release was lower during postreproduction, and
      mGnRH increased PGF2 alpha in prereproduction and reproduction. Androgens were
      higher during prereproduction, and mGnRH induced an androgens increase in
      prereproduction and reproduction. In T. carnifex testicular PGF2 alpha release
      was lower during reproduction, and mGnRH increased PGF2 alpha in prereproduction
      and reproduction. Androgens were higher in reproduction and lower in
      postreproduction, and mGnRH induced an androgens increase in reproduction.
      Estradiol-17 beta release was higher in postreproduction, and mGnRH induced an
      estradiol decrease in reproduction and an increase in postreproduction. These
      results seem to indicate the involvement of PGF2 alpha in the testicular
      reproductive activity, and a similar mGnRH mechanism of action, both in R.
      esculenta and in T. carnifex. In addition, taken together with previous studies,
      they seem to suggest that the relationship found between mGnRH and PGF2 alpha or
      sex steroids could be widespread in amphibians.

PMID- 1398020
TI  - Gonadotropin-releasing hormone from thai catfish: chromatographic and
      physiological studies.
AB  - Two forms of immunoreactive gonadotropin-releasing hormone (GnRH) were extracted
      from brain-pituitary tissues of Thai catfish, Clarias macrocephalus and C.
      batrachus. The peptides were detected using high performance liquid
      chromatography (HPLC) and radioimmunoassay (RIA). In both the HPLC systems,
      catfish GnRH-I eluted earlier than catfish GnRH-II and also eluted before the
      synthetic standards of mammalian, lamprey, chicken I, chicken II, and salmon
      GnRH. Hence, catfish GnRH-I appears to be the most hydrophilic GnRH family member
      because of this early elution from the HPLC. Catfish GnRH-II eluted in a position
      similar to that of chicken GnRH-II. This study suggests that catfish GnRH-I is a
      novel form of GnRH, whereas catfish GnRH-II is the same as chicken GnRH-II.
      Indirect evidence suggests that the catfish molecule is 10 amino acids in length
      and has an amide at the C-terminus. Moreover, the novel catfish GnRH appears to
      be different within the domain of amino acids 5 to 10 compared with mammalian
      GnRH because it is not recognized by antiserum B-6. An injection of native
      chicken GnRH-II was more effective than salmon or mammalian GnRH for induced
      ovulation in C. macrocephalus.

PMID- 1398021
TI  - Isolation and amino acid sequence of urotensin II from the sturgeon Acipenser
      ruthenus.
AB  - Urotensin II (UII) peptides have previously been isolated from the urophysis (the
      neurohemal organ of the caudal neurosecretory system) of several teleost fish,
      and the UII amino acid sequences have been determined. Chondrostean fish, such as
      the Acipenseridae (sturgeon), though without a distinct urophysis, also have a
      caudal neurosecretory system, which has been indicated by bioassay and
      immunological evidence to contain UII-like peptides. In the present studies, we
      investigated by UII radioimmunoassay the UII-like peptides in the spinal cord of
      three Acipenser species, and isolated and sequenced UII from one of them. As
      expected, much more UII immunoreactivity (UII-IR) was found in caudal than in
      anterior spinal cord extracts. In addition, caudal extracts from A. ruthenus were
      found to contain much more UII-IR (whether determined on a UII-IR/weight or UII
      IR/fish basis) than those from the larger A. stellatus and A. guldenstadti. UII
      was therefore isolated from A. ruthenus and its amino acid sequence was shown to
      be H-Gly-Ser-Thr-Ser-Glu-Cys-Phe-Trp-Lys-Tyr-Cys-Val-OH. This sequence is
      identical at positions 6-11 (the disulfide ring) with the known teleost UII
      peptides, and has acidic and hydrophobic amino acids at positions 5 and 12,
      respectively, as do the teleost UII peptides. Overall sequence identity with the
      various forms of teleost UII was 58-83%.

PMID- 1398023
TI  - Progesterone metabolism in vitro in the decapod crustacean, Penaeus monodon.
AB  - Thin-layer chromatography (TLC) and reversed-phase high-performance liquid
      chromatography (RP-HPLC) with on-line detection of radioactive steroids were
      applied to identify metabolites of [4-14C]progesterone incubated in vitro with
      prawn ovary. There was extensive metabolism of progesterone by stage II
      (vitellogenic) ovary of Penaeus monodon. The most abundant metabolites were 5
      alpha-pregnane derivatives together with two minor metabolites, 20 alpha
      hydroxypregn-4-en-3-one and 1,4-pregnadiene-3,20-dione. In contrast, a much lower
      level of progesterone metabolism was observed in stage 0 (immature) ovary of this
      species. The hepatopancreas, gill, and abdominal muscle of P. monodon all
      metabolised [4-14C]progesterone to varying degrees, generating materials similar
      to those produced by the ovary. A comparative study of progesterone metabolism in
      stage II ovary of Nephrops norvegicus indicated that one metabolite, 20 alpha
      hydroxypregn-4-en-3-one, was produced.

PMID- 1398022
TI  - Changes of LH level in the pituitary gland and plasma in hibernating frogs, Rana
      temporaria.
AB  - Pituitary and plasma luteinizing hormone (LH) levels were measured in female
      frogs, Rana temporaria, during and immediately after hibernation (0-4 degrees in
      darkness; 22-25 weeks) to study regulation of gonadotropin leading to
      posthibernation ovulation. Pituitary LH content began to rise progressively
      during the last third of hibernation (e.g., from starting levels of 5.3 +/- 0.09
      micrograms/gland, 1.5 micrograms/mg between 8 and 11 weeks, to 18.6 +/- 9.7
      micrograms/gland, 5.0 +/- 2.7 micrograms/mg at 19-22 weeks). Plasma LH increased
      in parallel, but with some delay (from 10 +/- 8 to 25 +/- 24 ng/ml). Frogs kept
      in light at low temperatures showed similar responses. Release of LH (rise in
      plasma levels with a drop in pituitary content) was observed during 32 hr
      immediately after termination of hibernation in association with the onset of
      ovulation. These data indicate the existence of regulatory mechanisms operating
      during hibernation under conditions of constant cold. Altogether, these and our
      previous results obtained after surgical deafferentiation of median eminence
      support the hypothesis of a progressive reduction of a CNS inhibition that
      results in the release of GnRH during hibernation in this frog.

PMID- 1398024
TI  - Growth and behavior of thyroid-deficient lizards (Sceloporus undulatus).
AB  - This study investigates thyroid control of growth and energy metabolism plus
      growth-dependent and growth-independent behavioral effects of thyroid
      manipulation in lizards. Experiments were done on surgically thyroidectomized
      (Tx) and sham-operated (Sh) yearling Sceloporus undulatus enclosed in their
      natural habitat. Lizards were placed in an outdoor enclosure in early August.
      Growth rate was measured and behavior was observed until mid-October.
      Subsequently, lizards were returned to the lab for measurements of plasma
      thyroxine (T4), standard metabolic rate (SMR), and running endurance.
      Thyroidectomy reduced plasma T4 from 4.3 +/- 0.56 ng/ml to undetectable levels (P
      = 0.006) and SMR by 44% (P less than 0.0001). Thyroid deficiency produced a
      threefold reduction in growth rate (Tx: 0.04 +/- 0.010 mm/day, n = 12 vs Sh: 0.11
      +/- 0.006 mm/day, n = 11, P less than 0.0001). Growth rate was correlated with
      SMR among individuals (length-specific: r = 0.55, P = 0.027, n = 16), even after
      statistical removal of mass and treatment effects. The total volume of oxygen
      consumed for standard metabolism during the growth period, as estimated from
      allometric equations, was correlated with cumulative growth (R2 = 0.94, P =
      0.013) and was significantly lower for thyroid-deficient lizards than for
      controls (P less than 0.0001). Distance moved in the field and running endurance
      on a treadmill both scaled on body mass (M0.98 +/- 0.418, P = 0.030 and M1.72 +/-
      0.763, P = 0.040, respectively), indicating that larger lizards moved farther and
      had greater stamina than their smaller counterparts. Neither of these behavioral
      factors was affected directly by thyroid status. Thyroid-deficient lizards were
      active for a smaller percentage of the day than controls (Tx: 42.6 +/- 5.7%, n =
      11 vs Sh: 57.4 +/- 3.2%, n = 12, P = 0.040), independent of differences in body
      size. On an interindividual basis, the frequency of activity was significantly
      correlated with SMR (r = 0.57, P = 0.020, n = 16) and growth rate (mass-specific:
      r = 0.47, P = 0.025, n = 23).

PMID- 1398025
TI  - Stably inherited killer activity in industrial yeast strains obtained by
      electrotransformation.
AB  - Killer-sensitive strains of Saccharomyces cerevisiae and Saccharomyces
      carlsbergensis were transformed by electroinjection using double-stranded RNA
      isolated from a superkiller strain. Various recipient strains were used: both
      thermo-resistant and thermo-sensitive as well as mutants of industrial strains.
      Conversion of respiratory competent (rho+) into respiratory deficient (rho-)
      strains (mutants) resulted in a significant increase of the yield of
      electrotransformants and/or of longterm killer stability. Electrotransformation
      of rho- mutants of distillery and brewery strains resulted in more than 100
      clones, which exhibited weak or strong killer activity over some or all of the
      experimental period of 10 months.

PMID- 1398026
TI  - The serotyping of Azospirillum spp. by cell-gold immunoblotting.
AB  - Ten Azospirillum strains were serotyped using the method of cell-gold
      immunoblotting (dot-blot immune-overlay assay). Colloidal gold-protein A
      conjugate was used. Antibodies raised against the whole cells showed strain
      specificity and interacted mainly with carbohydrate antigens on the cell surface.
      Immunological identity for A. brasilense Sp 245 and Sp 107 strains was found.
      Cell-gold immunoblotting can be recommended for serotyping of a wide variety of
      bacterial strains.

PMID- 1398027
TI  - Esterase electrophoresis compared with biotyping for epidemiological typing of
      Acinetobacter baumannii strains.
AB  - Forty-nine Acinetobacter baumannii strains belonging to three biotypes and
      isolated from four hospitals were differentiated by electrophoretic typing of
      their esterases. Six main kinds of esterases were distinguished by their spectra
      of hydrolytic activity toward seven synthetic substrates. The electrophoretic
      variations of these enzymes were used to define ten zymotypes among the three
      biotypes. Esterase electrophoresis appeared to be more sensitive than biotyping,
      and could represent an additional marker for epidemiological analysis.

PMID- 1398028
TI  - Plasmid involvement in the formation of a spontaneous bacteriophage insensitive
      mutant of Lactococcus lactis.
AB  - Lactococcus lactis subsp. lactis biovar. diacetylactis DPC721 is a spontaneous
      bacteriophage insensitive mutant of strain DPC220, isolated after challenge with
      an industrial bacteriophage, phi D1. Plasmid analysis demonstrated that the
      bacteriophage insensitivity was associated with the absence of two native DPC220
      plasmids (pAH82 and pAH33), and the presence of a novel plasmid (pAH90) in
      DPC721. The plasmids were transferred by conjugative mobilization to a plasmid
      free background where it was confirmed by restriction mapping that pAH90 is a co
      integrate formed by the precise recombination of pAH82 and pAH33. The resistance
      phenotype encoded by pAH90 was also active against two bacteriophage homologous
      for the plasmid-free strain. Plasmid pAH90 was shown to encode at least two
      independent resistance mechanisms, including an adsorption-inhibition mechanism
      and a restriction and modification system. The adsorption-inhibition mechanism
      encoded by the co-integrate plasmid was specific for one of the phage used in
      this study.

PMID- 1398029
TI  - Mode of replication, size and distribution of naturally occurring plasmids in
      Bacillus thuringiensis.
AB  - Cloned replication origin regions, derived from both small (4.9-7.5 MDa) and
      large (43-60 MDa) plasmids of Bacillus thuringiensis subspecies kurstaki strains
      HD73 and HD263 were used as hybridization probes in a Southern-blot analysis to
      assess both the size and horizontal distribution of native plasmid replicon
      groups among different subspecies of B. thuringiensis. In general, resident
      plasmids hybridizing to the replication origin regions derived from strains HD263
      and HD73 were more commonly found in kurstaki strains than in non-kurstaki
      strains, suggesting a non-random distribution of plasmid incompatibility groups.
      Replication origin regions derived from the large HD263 plasmids (43-60 MDa)
      hybridized almost exclusively with large plasmids (greater than 30 MDa) of widely
      varying sizes. In contrast, replication origin regions derived from small
      plasmids hybridized exclusively with small plasmids (less than 10 MDa) showing
      little size variation. These results are consistent with previous observations
      concerning the relationship between plasmid size, mode of replication, and
      structural stability.

PMID- 1398030
TI  - Efflux of choline and glycine betaine from osmoregulating cells of Escherichia
      coli.
AB  - We present evidence that glycine betaine (betaine) which was synthesized from
      choline was excreted and reaccumulated in osmoregulating cells of Escherichia
      coli. Choline which was accumulated in bet mutants defective in betaine synthesis
      was shown to be excreted in response to betaine uptake. Our data suggest that E.
      coli has efflux systems for betaine and choline which are independent of the
      uptake systems for these metabolites. The ProU system of E. coli, but not that of
      Salmonella typhimurium, can mediate low-affinity choline uptake.

PMID- 1398031
TI  - Serogroups of Escherichia coli strains producing cytotoxic necrotizing factors
      CNF1 and CNF2.
AB  - The serogroups of 396 necrotizing Escherichia coli of human and bovine origin
      isolated in Spain between 1979 and 1991 have been determined. The 270 cytotoxic
      necrotizing factor strains belonged to 22 different O serogroups; however, 84%
      (226 of 270) were of one of seven serogroups (O2, O4, O6, O14, O22, O75 and O83).
      Although necrotizing E. coli producing cytotoxic necrotizing factor 2 belonged to
      28 different serogroups, only six of them (O1, O3, O15, O55, O88 and O123)
      accounted for 60% (76 of 126) of cytotoxic necrotizing factor 2 strains.
      Furthermore, only 3% (4 of 126) of cytotoxic necrotizing factor 2 strains
      belonged to serogroups most common among strains producing cytotoxic necrotizing
      factor 1. The majority of necrotizing E. coli producing cytotoxic necrotizing
      factor 1 were obtained from human extraintestinal infections, whereas cytotoxic
      necrotizing factor 2 strains were isolated from stools of healthy and diarrhoeic
      calves.

PMID- 1398032
TI  - Sequence and functional analysis of the cloned Neisseria meningitidis CMP-NeuNAc
      synthetase.
AB  - The CMP-N-acetylneuraminic acid (CMP-NeuNAc) synthetase gene of Neisseria
      meningitidis group B is located on a 2.3-kb EcoRI fragment within the cps gene
      cluster. Nucleotide sequence determination of the gene encoding the CMP-NeuNAc
      synthetase revealed a 515-bp open reading frame that can encode a 18.9-kDA
      protein. A computer data base scan revealed a 59.4% identity to the CMP-NeuNAc
      synthetase gene of E. coli K1. Enzymatic activity was confirmed in vitro and in
      vivo. Transformation of the CMP-NeuNAc defective E. coli K1 strain EV5 with the
      meningococcal CMP-NeuNAc synthetase could complement the defect in E. coli.

PMID- 1398033
TI  - Cloning and characterization of an amplified DNA sequence in chromosomal DNA of
      Streptomyces aureofaciens 2201.
AB  - In strain 2201 of Streptomyces aureofaciens, a high copy number amplified DNA
      sequence (ADS-Sa2201) was found and characterized. The amplified sequence in the
      chromosomal DNA of this strain forms a stretch of about 10 kb tandemly repeated
      100-500 times. In this strain also, extrachromosomal copies of the repeated unit
      of the ADS-Sa2201 were found. In cloning experiments any autonomous replicon was
      found on ADS-Sa2201 and it thus can be presumed that the presence of the
      extrachromosomal copies of the repeated unit of ADS-Sa2201 is only a result of
      its excision from the chromosome. A part of the repeated unit of ADS-Sa2201 was
      also found in chromosomal DNA of strain 13 of S. aureofaciens. In this strain no
      part of ADS-Sa2201 is present extrachromosomally.

PMID- 1398034
TI  - Hydrogenase mutants of Alcaligenes eutrophus H16 show alterations in the electron
      transport system.
AB  - Mutations in the genes coding for the soluble and the membrane-bound hydrogenase
      of Alcaligenes eutrophus strain H16 significantly affected the expression of
      respiratory chain components. In lithoautotrophically grown wild type cells
      electron flow mainly proceeded via the cytochrome c oxidases. Mutants defective
      in the membrane-bound hydrogenase contained a 2- to 3-fold higher cytochrome a
      content than the wild type and cytochrome c oxidase of the aa3-type was
      preferentially used by these cells for substrate oxidation. Mutants impaired in
      the soluble hydrogenase revealed slow growth on hydrogen, presumably due to
      inefficient reverse electron flow mechanisms which provide the cells with NADH
      for autotrophic CO2-fixation. In this class of mutants the two quinol oxidases of
      the o- and d-type in addition to the co-type oxidase were the predominant
      electron-transport branches.

PMID- 1398036
TI  - Occurrence of cold-labile NAD-specific glutamate dehydrogenase in Bacillus
      species.
AB  - A nicotinamide adenine dinucleotide-specific glutamate dehydrogenase (NAD-GluDH;
      EC 1.4.1.3) inactivated by incubation at low temperatures was detected in several
      species of the genus Bacillus, including strains of B. cereus, B. laterosporus,
      B. lentus, B. panthotenicus, B. pasteurii, B. sphaericus, B. stearothermophilus,
      B. subtilis and B. thuringiensis. Incubation of cell-free extracts of these
      strains at 0 degrees C resulted in an 80-100% inactivation of NAD-GluDH activity
      within 120 min. The addition of 20% glycerol protected the enzyme from this
      inactivation in the cold. Strains of B. fastidiosus, B. licheniformis, B.
      macerans, B. megaterium and B. pumilus were found to lack NAD-GluDH activity.

PMID- 1398035
TI  - Characterisation of a novel repetitive DNA sequence from Mycobacterium bovis.
AB  - We report characterisation of three copies of a novel repeat sequence isolated
      from a Mycobacterium bovis genomic library. The repeat occurs within open reading
      frames, potentially encoding a conserved tandem array of a pentapeptide sequence
      with the consensus X-Gly-Asn-X-Gly. The tandem array is present up to five times
      in M. bovis and it is proposed that they may occur in a family of genes
      expressing functionally related proteins. We postulate that these proteins may
      play a role in binding of M. bovis to host cell receptors.

PMID- 1398037
TI  - Cosmid pJAR4, a novel Streptomyces-Escherichia coli shuttle vector for the
      cloning of Streptomyces operons.
AB  - A novel shuttle cosmid vector (pJAR4), based on pK505, was constructed for the
      cloning of Streptomyces DNA. It is a low-copy-number vector which determines
      hygromycin B-resistance as a selective marker and was used to clone the puromycin
      biosynthesis pathway from Streptomyces alboniger. Cosmids pJAR4 and pKC505 (which
      determines apramycin-resistance) stably co-transform both Streptomyces lividans
      and Streptomyces griseofuscus.

PMID- 1398038
TI  - Metal ion-catalysed hydrolysis of ampicillin in microbiological growth media.
AB  - Anodic stripping voltammetry of bacterial growth medium containing copper(II) and
      ampicillin shows that Cu(II) is complexed by the antibiotic and that this complex
      decomposes to give Cu(II) complexes with ligands derived from ampicillin. At pH
      7, substantial decomposition of ampicillin occurs over a few minutes, and even
      the very low levels of Cu(II) in Chelex-extracted medium are able effectively to
      catalyse the decomposition. The significance of this observation was shown during
      the screening of an Escherichia coli cosmid library for clones exhibiting
      increased resistance to Zn(II), Co(II) or Cd(II); the unexpected growth of the
      ampicillin-sensitive host E. coli strain on Luria-Bertani plates containing
      ampicillin and any of these metals was attributed to metal ion-catalysed
      decomposition of ampicillin. The instability of ampicillin (and other beta-lactam
      antibiotics) to metal ion-catalysed hydrolysis means that great care must be
      taken to ensure that such reactions do not occur in growth media. Furthermore, it
      is clear that double selection for resistance to ampicillin and metals such as
      Cu(II), Zn(II), Co(II) and Cd(II) is impossible.

PMID- 1398039
TI  - Heterotrophic sulfur reduction by Thermotoga sp. strain FjSS3.B1.
AB  - Thermotoga sp. strain FjSS3.B1 was able to reduce sulfur to sulfide when grown on
      a mineral medium with glucose as the sole carbon and energy source. There was no
      increase in specific growth yield coupled to sulfur reduction, but the specific
      growth rate, final growth yield, and tolerance of H2 were all increased in the
      presence of sulfur. At dissolved H2 concentrations, of 550 to 600 mumol/l (at 77
      degrees C) growth was not possible unless sulfur was added. Glucose was fermented
      via the Embden-Meyerhof-Parnas pathway to lactate, acetate, H2 and CO2 (and other
      unidentified minor products). The thermodynamic problems associated with the
      relatively high redox potential electrons from the 1,3
      bisphosphoglycerate/glyceraldehyde 3-phosphate couple (E'0 = -350 mV) are
      overcome by reducing sulfur to sulfide (E'0 = -270 mV) rather than the
      energetically unfavourable production of H2 (E'0 = -414 mV). Under high hydrogen
      partial pressures there was increased production of lactate as an alternative
      electron sink. The results indicate that sulfur reduction operates primarily as
      an electron sink rather than as a detoxification reaction or energy-generating
      mechanism.

PMID- 1398040
TI  - Sequence of the gene encoding type F neurotoxin of Clostridium botulinum.
AB  - Primers designed to conserved regions of botulinum and tetanus clostridial toxins
      were used to amplify DNA fragments from non-proteolytic Clostridium botulinum
      type F (202F) DNA using polymerase chain reaction technology. The fragments were
      cloned and the complete nucleotide sequence of the gene encoding type F toxin
      determined. Analysis of the nucleotide sequence demonstrated the presence of an
      open frame encoding a protein of 1274 amino acids, similar to other botulinum
      neurotoxins. Upstream of the toxin gene is the end of an open reading frame which
      encodes the C-terminus of a protein with homology to non-toxic-non-hemagglutinin
      component of type C progenitor toxin.

PMID- 1398041
TI  - Tris-dependent site-specific cleavage of Streptomyces lividans DNA.
AB  - During conventional gel electrophoresis, Streptomyces lividans DNA undergoes site
      specific double-strand cleavage at the positions of closely opposed unstable
      modifications introduced into the DNA in vivo. We investigated this
      electrophoretic instability and demonstrated that it was dependent on Tris. Tris
      buffer was activated at the anode to generate a nucleolytic species; prior to
      activation, Tris was not able to cleave the DNA. The nucleolytic species was
      shown to react with thiourea, which could thus protect the DNA from strand
      cleavage. Non-degradative electrophoresis of the DNA could also be achieved in an
      alternative buffer such as Hepes.

PMID- 1398042
TI  - Metabolism of 3-methyldiphenyl ether by Sphingomonas sp. SS31.
AB  - The bacterium Sphingomonas sp. SS31, which was obtained from the diphenyl ether
      degrading strain Sphingomonas sp. SS3 by an adaptation process, utilized 3
      methyldiphenyl ether for growth in addition to diphenyl ether. The initial
      enzymatic attack onto this compound proceeded by a regioselective, but non
      specific dioxygenation at the carbon carrying the ether bridge and the adjacent
      carbon of the unsubstituted as well as the methyl-substituted aromatic nucleus.
      Upon spontaneous decomposition, the resulting unstable hemiacetal structure
      yielded 3-methylphenol and catechol, or phenol, 3-methylcatechol, and 4
      methylcatechol, respectively. Phenol and 3-methylphenol were oxidized to the
      corresponding catechols which, after subsequent ortho-cleavage, were channeled
      into the oxoadipate pathway.

PMID- 1398043
TI  - Pedigree analysis of blood pressure in subjects from rural Greece and relatives
      who migrated to Melbourne, Australia.
AB  - Diastolic blood pressure readings taken in 1983-1984 on 1,474 Greek individuals
      (628 living on the island of Levkada, 846 relatives having migrated to Melbourne,
      Australia) from 204 two generational pedigrees were analysed. Blood pressure was
      regressed as a quadratic in age by sex and migrant status, and on temperature.
      Variance increased with age and was greater in migrant males. The covariance
      between relatives in different countries was significant. Variation was modeled
      by a multivariate normal model for pedigree analysis in terms of genetic effects,
      a common environment effect, and effects particular to an individual. The genetic
      component was 25.9 mm Hg2, independent of sex and migrant status. Importantly,
      the common environment component was not significant. The third component was
      greatest in migrant males. Spouse correlation was -0.09 (SE = 0.03). Exclusion of
      86 individuals who reported currently receiving medication for elevated blood
      pressure stabilised the variance and decreased the genetic component. The data
      suggest that familial aggregation of diastolic blood pressure is due to genetic
      factors which produce the same variation in males and females, living on Levkada
      or in Melbourne. Nongenetic factors explain the greater variation in blood
      pressure of migrant males living in Melbourne.

PMID- 1398044
TI  - Estimation of the frequency of isoform-genotype discrepancies at the
      apolipoprotein E locus in heterozygotes for the isoforms.
AB  - Estimates of the impact of apolipoprotein E (apo E) alleles coding for the three
      common isoforms on plasma lipid levels assume genetic homogeneity among the
      genotype classes. To test this assumption, we have determined the apo E genotype
      at the two common polymorphic sites (amino acids 112 and 158) by DNA
      amplification and hybridisation with allele-specific oligoprobes, in 195
      unrelated Caucasian participants of the Rochester Family Heart Study previously
      classified as heterozygotes by isoelectric focusing (IEF). Fourteen discordant
      samples were initially detected. Repeat typing of these samples by both methods
      resolved nine discrepancies and analysis of additional blood samples from the
      remaining five individuals eliminated a further four discrepancies. The only
      truly discordant allele was found in a female subject who had an E3 isoform with
      the common E2 (Cys112, Cys158) genotype. Transmission of this allele from the
      mother was demonstrated. From these results, we estimate the frequency of
      discrepancies between isoforms and common genotypes to be 0.25% in this
      population. Allele misclassification was caused by poor amplification of the DNA
      in six samples and superimposition of glycosylated and nonglycosylated apo E
      isoforms on isoelectric focusing gels in five samples. We conclude that the
      assumption of genetic homogeneity among genotype classes is valid and that
      misclassification due to technical difficulties is more frequent than true
      discordancies.

PMID- 1398045
TI  - Effect of cohort differences in smoking prevalence on models of lung cancer
      susceptibility.
AB  - Data on 337 lung cancer families were analyzed to determine if known cohort
      differences in parental cigarette consumption influence parameters from a
      segregation analysis. Previous results suggested that, after allowing for an
      individual's pack-years of tobacco exposure, Mendelian codominant inheritance of
      an allele that produced an earlier age of onset provided a good fit to the data.
      In the present study, the data were split into two groups of families: probands
      age 60 and over (born before WWI) and probands younger than age 60. This
      partition of the data by age of the proband was done to separate families in
      which there were parents who were less likely to smoke from those with parents
      more likely to smoke--predicated on the known increase of smoking prevalence
      after World War I. For the younger proband families (those with parents more
      likely to smoke), only Mendelian codominant inheritance adequately fit the data.
      The hypotheses of no major type, environmental transmission, and Mendelian
      dominant or recessive inheritance were rejected. In contrast to our earlier
      findings, the estimate of population susceptibility increased from 28% in the
      total data to 60% in this subset. In the older proband families (those with
      parents less likely to smoke), the no major type and environmental hypotheses
      were rejected; further, none of the Mendelian models could be distinguished. Our
      results demonstrate that cohort differences, probably in exposure to tobacco, can
      confound parameters of a segregation analysis, and suggest that the genetic
      component of lung cancer may be greater than previously estimated. It further
      suggests that susceptibility to lung cancer occurs as a function of
      susceptibility to the effects of tobacco smoking.

PMID- 1398046
TI  - Elementary methods for the analysis of dichotomous outcomes in unselected samples
      of twins.
AB  - This paper presents an elementary statistical method for analyzing dichotomous
      outcomes in unselected samples of twin pairs using stratified estimators of the
      odds ratio. The methodology begins by first randomly designating one member of
      each twin pair as an "index" twin and the other member as the "co-twin."
      Stratifying on zygosity, odds ratios are used to measure the association between
      disease in the index twin and disease in the co-twin. From these zygosity
      specific tables we calculate the Woolf-Haldane estimator of the common odds ratio
      (psi F, the weighted average of the zygosity-specific odds ratios), the Mantel
      Haenszel test statistic (chi 2M-H) for the common odds ratio, and a test (chi 2G)
      for the difference in the zygosity-specific odds ratios. In this application, psi
      F provides an estimate of the familial association for disease and the
      accompanying chi 2M-H provides a test of the null hypothesis, psi F = 1 (i.e.,
      there is no evidence for a familial influence on disease). The chi 2G is a test
      of the null hypothesis that psi MZ = psi DZ; a significant value for chi 2G
      suggests a genetic influence on disease (assuming that the observed odds ratios
      follow a pattern where psi MZ greater than psi DZ). A new test statistic (chi 2c)
      is proposed that incorporates the expectation that psi MZ = psi 2DZ under a
      purely additive genetic model with no common environmental effects. A significant
      value of chi c2 indicates that the different odds ratios across zygosity are
      partly due to common environmental influences. Conversely, a nonsignificant value
      of chi 2c is an indication that the zygosity-specific odds ratios are due solely
      to additive genetic effects and not to common environment. This basic approach is
      extended to examine the effects of measured indicators of the specific
      environment and the assessment of certain forms of gene by environment
      interaction. All of the methods are easily understood, highly flexible, readily
      computed using a hand calculator, and incorporate the inherent genetic
      information contained within twin samples.

PMID- 1398047
TI  - On the beginnings of somatic cell hybridization: Boris Ephrussi and chromosome
      transplantation.

PMID- 1398048
TI  - Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces
      cerevisiae.
AB  - Heteroduplexes formed between genes on homologous chromosomes are intermediates
      in meiotic recombination. In the HIS4 gene of Saccharomyces cerevisiae, most
      mutant alleles at the 5' end of the gene have a higher rate of meiotic
      recombination (gene conversion) than mutant alleles at the 3' end of the gene.
      Such gradients are usually interpreted as indicating a higher frequency of
      heteroduplex formation at the high conversion end of the gene. We present
      evidence indicating that the gradient of conversion at HIS4 primarily reflects
      the direction of mismatch repair rather than the frequency of heteroduplex
      formation. We also identify a site located between the 5' end of HIS4 and the 3'
      end of BIK1 that stimulates heteroduplex formation at HIS4 and BIK1.

PMID- 1398049
TI  - Isolation of Neurospora crassa A mating type mutants by repeat induced point
      (RIP) mutation.
AB  - In the filamentous fungus, Neurospora crassa, mating type is regulated by a
      single locus with alternate alleles, termed A and a. The mating type alleles
      control entry into the sexual cycle, but during vegetative growth they function
      to elicit heterokaryon incompatibility, such that fusion of A and a hypha results
      in death of cells along the fusion point. Previous studies have shown that the A
      allele consists of 5301 bp and has no similarity to the a allele; it is found as
      a single copy and only within the A genome. The a allele is 3235 bp in length and
      it, too, is found as a single copy within the a genome. Within the A sequence, a
      single open reading frame (ORF) of 288 amino acids (mt A-1) is thought to confer
      fertility and heterokaryon incompatibility. In this study, we have used repeat
      induced point (RIP) mutation to identify functional regions of the A idiomorph.
      RIP mutations in mt A-1 resulted in the isolation of sterile, heterokaryon
      compatible mutants, while RIP mutations generated in a region outside of mt A-1
      resulted in the isolation of mutants capable of mating, but deficient in
      ascospore formation.

PMID- 1398050
TI  - Correlation between pairing initiation sites, recombination nodules and meiotic
      recombination in Sordaria macrospora.
AB  - The decrease of meiotic exchanges (crossing over and conversion) in two mutants
      of Sordaria macrospora correlated strongly with a reduction of chiasmata and of
      both types of "recombination nodules." Serial section reconstruction electron
      microscopy was used to compare the synapsis pattern of meiotic prophase I in wild
      type and mutants. First, synapsis occurred but the number of synaptonemal complex
      initiation sites was reduced in both mutants. Second, this reduction was
      accompanied by, or resulted in, modifications of the pattern of synapsis. Genetic
      and synaptonemal complex maps were compared in three regions along one chromosome
      arm divided into well marked intervals. Reciprocal exchange frequencies and
      number of recombination nodules correlated in wild type in the three analyzed
      intervals, but disparity was found between the location of recombination nodules
      and exchanges in the mutants. Despite the twofold exchange decrease, sections of
      the genome such as the short arm of chromosome 2 and telomere regions were
      sheltered from nodule decrease and from pairing modifications. This indicated a
      certain amount of diversity in the control of these features and suggested that
      exchange frequency was dependent not only on the amount of effective pairing but
      also on the localization of the pairing sites, as revealed by the synaptonemal
      complex progression in the mutants.

PMID- 1398051
TI  - Molecular population genetics of an electrophoretically monomorphic protein in
      the alcohol dehydrogenase region of Drosophila pseudoobscura.
AB  - Nucleotide sequence data from the alcohol dehydrogenase (Adh) region of 18
      isochromosomal strains of Drosophila pseudoobscura were used to determine whether
      the lack of amino acid polymorphism in ADH results from a low neutral mutation
      rate or a recent directional selection event. We estimated the neutral mutation
      parameter, 4Nmu, in synonymous sites for 17 subregions of Adh. The nucleotide
      diversity data were tested for departures from an equilibrium neutral model with
      two statistical tests. The Tajima test and the Hudson, Kreitman and Aguade test
      each failed to reject a neutral model. These results suggest that the ADH enzyme
      of D. pseudoobscura lacks amino acid polymorphisms because the neutral mutation
      rate of nonsynonymous sites is low. The neutral mutation parameter for synonymous
      sites is heterogeneous between domains of the Adh region. These data indicate
      that selective constrains on synonymous sites can vary between functional
      domains.

PMID- 1398052
TI  - Differentiation of a male-specific muscle in Drosophila melanogaster does not
      require the sex-determining genes doublesex or intersex.
AB  - A pair of muscles span the fifth abdominal segment of male but not female
      Drosophila melanogaster adults. To establish whether genes involved in the
      development of other sexually dimorphic tissues controlled the differentiation of
      sex-specific muscles, flies mutant for five known sex-determining genes were
      examined for the occurrence of male-specific abdominal muscles. Female flies
      mutant for alleles of Sex-lethal, defective in sex determination, or null alleles
      of transformer or transformer-2 are converted into phenotypic males that formed
      male-specific abdominal muscles. Both male and female flies, when mutant for null
      alleles of doublesex, develop as nearly identical intersexes in other somatic
      characteristics. Male doublesex flies produced the male-specific muscles, whereas
      female doublesex flies lacked them. Female flies, even when they inappropriately
      expressed the male-specific form of doublesex mRNA, failed to produce the male
      specific muscles. Therefore, the wild-type products of the genes Sex-lethal,
      transformer and transformer-2 act to prevent the differentiation of male-specific
      muscles in female flies. However, there is no role for the genes doublesex or
      intersex in either the generation of the male-specific muscles in males or their
      suppression in females.

PMID- 1398054
TI  - Frequencies of mitochondrial DNA haplotypes in laboratory cage populations of the
      mosquito, Aedes albopictus.
AB  - A laboratory cage experiment was undertaken to study changes over time in the
      frequencies of two mitochondrial DNA (mtDNA) haplotypes in the mosquito, Aedes
      albopictus, under two conditions: bidirectionally compatible matings and
      unidirectionally incompatible matings. Frequencies were monitored for 10
      generations in three replicate cages for each of the two conditions above. In
      cages with bidirectionally compatible strains, changes in haplotype frequencies
      were nondirectional and neither haplotype increased in frequency. Statistical
      analysis of relative proportions of the two haplotypes in each generation
      indicated that the magnitude of the observed fluctuations could be expected under
      an assumption of random genetic drift alone. In cages with unidirectionally
      incompatible matings, mtDNA of females that lay inviable eggs upon mating with
      males of another strain, decreased significantly in the F1 generation and was
      completely replaced in the F2 generation.

PMID- 1398055
TI  - Mitochondrial DNA length variation and heteroplasmy in populations of white
      sturgeon (Acipenser transmontanus).
AB  - Southern blot analysis was used to quantify the extent of mtDNA D-loop length
      variation in two populations of white sturgeon, Acipenser transmontanus. Over 42%
      of individuals were heteroplasmic for up to six different mtDNA length variants
      attributable to varying copy numbers of an 82-bp repeat sequence. Chi-square
      analyses revealed that the frequencies of length genotypes and the incidence of
      heteroplasmy were significantly different between Fraser and Columbia River
      sturgeon populations but not between restriction site haplotypes. Heteroplasmic
      fish have, on average, higher copy number than homoplasmic fish. Forty-five of
      101 homoplasmic individuals carry only a single copy of the repeat, while none of
      the 73 heteroplasmic fish has the single repeat as the predominant variant. On
      the basis of differences in frequency distributions of copy number within and
      between fish, we suggest that (1) heteroplasmy is maintained by high recurrent
      mutation of multiple copy genomes, favoring increased copy number and (2) the
      mutation pressure toward higher copy number heteroplasmy is partially offset by
      selection to reduced genome size and segregation to the homoplasmic condition.

PMID- 1398053
TI  - Variable rates of evolution among Drosophila opsin genes.
AB  - DNA sequences and chromosomal locations of four Drosophila pseudoobscura opsin
      genes were compared with those from Drosophila melanogaster, to determine factors
      that influence the evolution of multigene families. Although the opsin proteins
      perform the same primary functions, the comparisons reveal a wide range of
      evolutionary rates. Amino acid identities for the opsins range from 90% for Rh2
      to more than 95% for Rh1 and Rh4. Variation in the rate of synonymous site
      substitution is especially striking: the major opsin, encoded by the Rh1 locus,
      differs at only 26.1% of synonymous sites between D. pseudoobscura and D.
      melanogaster, while the other opsin loci differ by as much as 39.2% at synonymous
      sites. Rh3 and Rh4 have similar levels of synonymous nucleotide substitution but
      significantly different amounts of amino acid replacement. This decoupling of
      nucleotide substitution and amino acid replacement suggests that different
      selective pressures are acting on these similar genes. There is significant
      heterogeneity in base composition and codon usage bias among the opsin genes in
      both species, but there are no consistent relationships between these factors and
      the rate of evolution of the opsins. In addition to exhibiting variation in
      evolutionary rates, the opsin loci in these species reveal rearrangements of
      chromosome elements.

PMID- 1398056
TI  - Traits that influence longevity in mice: a second look.
AB  - Analysis of genetic interactions in the F2 of an intercross of (C57BL/6 x DBA/2)
      F1J revealed influences of genetic factors on life span. Females lived longer
      than males. Dilute brown females died sooner than females of other colors. H-2b/H
      2b males died sooner than H-2b/H-2d or H-2d/H-2d males, except that among dilute
      brown males those of typeH-2b/H-2d died sooner. Cluster analysis suggested that
      male and female genotypes each fall into two groups, with female dilute brown
      mice having shorter lives than other females, and male H-2b/H-2b mice except
      dilute brown and dilute brown H-2b/H-2d mice having shorter lives than other
      males. The association of heterozygosity with life span was clearer in females
      than in males, yet the longest-lived female genotype was homozygous H-2d/H-2d, of
      dominant Black phenotype at the Brown locus of chromosome 4, and homozygous dd at
      the Dilute locus of chromosome 9. The shortest-lived females were dilute brown H
      2b/H-2b. The longest-lived and shortest-lived male genotypes were dilute brown H
      2d/H-2d and dilute brown H-2b/H-2d, respectively. Although histological findings
      at postmortem differed between the sexes, there was no association of particular
      disorders with other genetic markers. The importance of H-2 in males was
      confirmed, but the allelic effects were perturbed, possibly by the absence of
      Sendai infection in this experiment. Overall our studies suggest that genetic
      influences on life span involve interactions between loci, and allelic
      interactions may change with viral infections or other environmental factors.

PMID- 1398058
TI  - Simulation study of a multigene family, with special reference to the evolution
      of compensatory advantageous mutations.
AB  - We investigate the evolution of a multigene family incorporating the forces of
      drift, mutation, gene conversion, unequal crossing over and selection. The use of
      simulation studies is required due to the complexity of the model. Selection is
      modeled in two modes: positive selection as a function of the number of different
      beneficial alleles and negative selection against deleterious alleles. We assume
      that gene conversion is unbiased, and that all mutations are initially
      deleterious. Compensation between mutants creates beneficial and neutral alleles,
      and allowances are made for compensatory mutations either within or between the
      members of a multigene family. We find that gene conversion can enhance the rate
      of acquisition of compensatory advantageous mutations when genes are redundant.

PMID- 1398057
TI  - The polar-lethal Ovum mutant gene maps to the distal portion of mouse chromosome
      11.
AB  - Genome imprinting is the process by which identical alleles at a particular locus
      may be rendered functionally different depending on the sex of the parent
      contributing the allele. While several mutations in imprinted genes have been
      defined, no variants in the regulatory system that gives rise to imprinting have
      been described. Here we report our genetic analysis of the behavior of the
      interstrain, polar, embryonic-lethal phenotype known as the "DDK syndrome." We
      have mapped the interstrain, polar-lethal region of the genome to the distal
      portion of mouse chromosome 11, near the Xmv-42 locus. We propose that the lethal
      phenotype is not caused by a standard mutation, but by aberrant imprinting of a
      gene within this region.

PMID- 1398059
TI  - Comparative effects of pollen and seed migration on the cytonuclear structure of
      plant populations. II. Paternal cytoplasmic inheritance.
AB  - We continue our study of the effects of pollen and seed migration on the
      cytonuclear structure of mixed-mating plant populations by analyzing two
      deterministic continent-island models under the critical assumption of paternal
      cytoplasmic inheritance. The major results of this study that contrast with our
      previous conclusions based on maternal cytoplasmic inheritance are (i) pollen
      gene flow can significantly affect the cytonuclear structure of the island
      population, and in particular can help to generate cytonuclear disequilibria that
      greatly exceed the magnitude of those that would be produced by seed migration or
      mixed mating alone; (ii) with simultaneous pollen and seed migration, nonzero
      cytonuclear disequilibria will be maintained not only when there is
      disequilibrium in the immigrant pollen or seeds, but also through a variety of
      intermigrant admixture effects when the two pools of immigrants differ
      appropriately in their cytonuclear compositions; (iii) either immigrant pollen or
      immigrant seeds can generate disequilibria de novo in populations with initially
      random cytonuclear associations, but pollen migration alone generally produces
      lower levels of disequilibrium than does comparable seed migration, especially at
      high levels of self-fertilization when the overall fraction of immigrant pollen
      is low; (iv) the equilibrium state of the island population will be influenced by
      the rate of pollen gene flow whenever there is either allelic disequilibrium in
      the immigrant pollen or simultaneous seed migration coupled with different
      cytoplasmic or nuclear allele frequencies in immigrant pollen and seeds or
      nonzero allelic disequilibrium in either immigrant pool. The estimation of pollen
      migration should therefore be facilitated with paternal cytoplasmic inheritance
      relative to the case of maternal cytoplasmic inheritance. These basic conclusions
      hold whether the population is censused as seeds or as adults, but with
      simultaneous pollen and seed migration, the relationship between census time and
      the ability to detect nonrandom cytonuclear associations is complex. When
      migration is through pollen alone, however, the cytonuclear structure of the
      island population is independent of the life stage censused.

PMID- 1398060
TI  - Testing for equality of evolutionary rates.
AB  - A likelihood ratio test is presented for comparing rates of evolutionary change
      in the paths of descent leading to two species. The test is compared to previous
      relative rate tests based on variances of estimated numbers of base
      substitutions. The likelihood approach allows for different transversion and
      transition rates, and when these rates are actually different, the likelihood
      ratio test can be much more powerful than the variance-based tests. For single
      parameter mutation models, however, the two tests have similar power. The tests
      are applied to a set of chloroplast sequences from several species of grasses,
      and additional indications of significantly different rates leading to barley
      were found with the likelihood ratio test.

PMID- 1398061
TI  - Inferring selective history from multilocus frequency data: Wright meets the
      Hamiltonian.
AB  - We describe a method to study characteristics of the dynamics of multilocus
      population genetic models without specifying the form of selection a priori. Our
      approach consists of specifying initial and final genotypic frequencies (either
      completely or partially) and then determining the minimum time to go from the
      initial condition to the final condition according to a continuous time genetic
      model, with arbitrary constraints on the strength and possibly the form of
      selection. In analyzing a two-locus, two-allele model with this approach, we show
      that--so long as r is not much larger than s--substantial linkage disequilibrium
      can be generated from an initial state of linkage equilibrium in a few hundred
      generations. We also show that unless recombination is much larger than
      selection, there is only weak dependence on r of the minimum time to reach a
      specified state. Thus, similar strengths of selection can lead to similar levels
      of disequilibrium over a fixed time and a range of small recombination rates.
      This implies that, within the level of a single gene, selection cannot in general
      be assumed to lead to any particular relationship between recombination rate and
      levels of disequilibrium. We indicate a number of other ways in which our method
      can be useful in asking theoretical questions and in interpreting data.

PMID- 1398062
TI  - A colony color assay for Saccharomyces cerevisiae mutants defective in
      kinetochore structure and function.
AB  - We have designed a colony color assay for monitoring centromere DNA-protein
      interactions in yeast (Saccharomyces cerevisiae). The assay is based on the
      ability of centromere DNA sequences to block (in cis) transcription initiated
      from a hybrid CEN-GAL1 promoter. Using a IacZ reporter gene under control of the
      CEN-GAL1 promoter, we screened colonies derived from mutagenized cells for a blue
      color phenotype indicative of derepression of the hybrid construct. A limited
      screen in which a 61-bp CEN11 DNA fragment containing an intact CDEIII subregion
      plus flanking sequences was used as the "pseudo-operator" led to the
      identification of mutations (blu) in three complementation groups. The blu1
      mutants exhibited a decrease in activity of the major CEN DNA-binding proteins in
      vitro. The BLU1 gene was shown to be identical to the previously isolated SPT3
      gene, known to be involved in the transcriptional regulation of a subset of yeast
      genes. Our results indicate that the BLU1/SPT3 gene product may also be required
      to maintain optimal levels of functional centromere DNA-binding proteins.

PMID- 1398063
TI  - Molecular genetic studies of the Cdc7 protein kinase and induced mutagenesis in
      yeast.
AB  - The Saccharomyces cerevisiae CDC7 gene encodes a protein kinase that functions in
      DNA replication, repair, and meiotic recombination. The sequence of several
      temperature-sensitive (ts) cdc7 mutations was determined and correlated with
      protein kinase consensus domain structure. The positions of these ts alleles
      suggests some general principles for predicting ts protein kinase mutations.
      Pedigree segregation lag analysis demonstrated that all of the mutant proteins
      are less active or less stable than wild-type Cdc7p. Two new mutations were
      constructed, one by site-directed and the other by insertional mutagenesis. All
      of the cdc7 mutants were assayed for induced mutagenesis in response to mutagenic
      agents at the permissive temperature. Some cdc7 mutants were found to be
      hypomutable, while others are hypermutable. The differences in mutability are
      observed most clearly when log phase cells are used. Both hypo- and
      hypermutability are recessive to wild type. Cdc7p may participate in DNA repair
      by phosphorylating repair enzymes or by altering chromatin structure to allow
      accessibility to DNA lesions.

PMID- 1398064
TI  - Possible cross-regulation of phosphate and sulfate metabolism in Saccharomyces
      cerevisiae.
AB  - CP1 (encoded by the gene CEP1) is a sequence-specific DNA binding protein of
      Saccharomyces cerevisiae that recognizes a sequence element (CDEI) found in both
      yeast centromeres and gene promoters. Strains lacking CP1 exhibit defects in
      growth, chromosome segregation and methionine biosynthesis. A YEp24-based yeast
      genomic library was screened for plasmids which suppressed the methionine
      auxotrophy of a cep1 null mutant. The suppressing plasmids contained either CEP1
      or DNA derived from the PHO4 locus. Subcloning experiments confirmed that
      suppression correlated with increased dosage of PHO4. PHO4c, pho80 and pho84
      mutations, all of which lead to constitutive activation of the PHO4 transcription
      factor, also suppressed cep1 methionine auxotrophy. The suppression appeared to
      be a direct effect of PHO4, not a secondary effect of PHO regulon derepression,
      and was PHO2-dependent. Spontaneously arising extragenic suppressors of cep1
      methionine auxotrophy were also isolated; approximately one-third of them were
      alleles of pho80. While PHO4 overexpression suppressed the methionine auxotrophy
      of a cep1 mutant, CEP1 overexpression failed to suppress the phenotype of a pho4
      mutant; however, a cep1 null mutation suppressed the low inorganic phosphate
      growth deficiency of a pho84 mutant. The results may suggest that phosphate and
      sulfate metabolism are cross-regulated.

PMID- 1398065
TI  - MAK10, a glucose-repressible gene necessary for replication of a dsRNA virus of
      Saccharomyces cerevisiae, has T cell receptor alpha-subunit motifs.
AB  - The MAK10 gene is necessary for the propagation of the L-A dsRNA virus of the
      yeast Saccharomyces cerevisiae. We have isolated MAK10 from selected phage lambda
      genomic DNA clones that map near MAK10. This gene encodes a 733-amino acid
      protein with several regions of similarity to T cell receptor alpha-subunit V
      (variable) regions. We show that MAK10 is essential for optimal growth on
      nonfermentable carbon sources independent of its effect on L-A. Although loss of
      L-A by mak10-1 mutants is partially suppressed by loss of the mitochondrial
      genome, no such suppression of a mak10::URA3 mutation was observed. Using MAK10
      lacZ fusions we show that MAK10 is expressed at a very low level and that it is
      glucose repressed. The highest levels of expression were seen in tup1 and cyc8
      mutants, known to be defective in glucose repression. These results suggest that
      the mitochondrial genome and L-A dsRNA compete for the MAK10 protein.

PMID- 1398066
TI  - An examination of adaptive reversion in Saccharomyces cerevisiae.
AB  - Reversion to Lys+ prototrophy in a haploid yeast strain containing a defined lys2
      frameshift mutation has been examined. When cells were plated on synthetic
      complete medium lacking only lysine, the numbers of Lys+ revertant colonies
      accumulated in a time-dependent manner in the absence of any detectable increase
      in cell number. An examination of the distribution of the numbers of early
      appearing Lys+ colonies from independent cultures suggests that the mutations to
      prototrophy occurred randomly during nonselective growth. In contrast, an
      examination of the distribution of late appearing Lys+ colonies indicates that
      the underlying reversion events occurred after selective plating. No accumulation
      of Lys+ revertants occurred when cells were starved for tryptophan, leucine or
      both lysine and tryptophan prior to plating selectively for Lys+ revertants.
      These results indicate that mutations accumulate more frequently when they confer
      a selective advantage, and are thus consistent with the occurrence of adaptive
      mutations in yeast.

PMID- 1398067
TI  - Cyclin E/cdk2 and cyclin A/cdk2 kinases associate with p107 and E2F in a
      temporally distinct manner.
AB  - Cyclin E is classified as a putative G1 cyclin on the basis of its cyclic pattern
      of mRNA expression, with maximal levels being detected near the G1/S boundary. We
      report here that cyclin E is found associated with the transcription factor E2F
      in a temporally regulated fashion. E2F is known to be a critical transcription
      factor for the expression of some S phase-specific proteins and is thought to be
      important for a series of others. Antisera specific for cyclin E were raised and
      used to demonstrate an association between cyclin E and E2F. This cyclin E/E2F
      complex was seen in a variety of human cell lines from various tissues, but its
      appearance was detected primarily during the G1 phase of the cell cycle. The
      cyclin E/E2F association decreased as cells entered S phase, just as the
      association of E2F with cyclin A became detectable. We characterized the cyclin E
      E2F complex further to show that both the cyclin-dependent kinase-2 (cdk2) and
      p107 were present. Therefore, the p107/E2F complex is associated with two
      different cdk2 kinase complexes--one containing cyclin A and the other containing
      cyclin E--and the appearance of these complexes is temporally regulated during
      the cell cycle. The presence of cyclin E/E2F complexes in the G1 phase suggests a
      role for cyclin E in the control of genes required for the G1-to-S transition.

PMID- 1398068
TI  - Site-specific binding of wild-type p53 to cellular DNA is inhibited by SV40 T
      antigen and mutant p53.
AB  - Wild-type p53 protein was shown to bind specifically to DNA sequences within SV40
      (Bargonetti et al. 1991), the human ribosomal gene cluster (RGC) (Kern et al.
      1991a), and the murine muscle creatine kinase gene (MCK) (Zambetti et al. 1992).
      However, a direct comparison of these three sites was not performed. Here we
      demonstrate, by filter binding and gel mobility-shift assays, that wild-type p53
      binds with similar affinities to MCK and RGC sites but less tightly to the SV40
      site. We examined the effects of two candidate regulators of p53 function, SV40
      large T antigen and oncogenic mutant p53, on the binding of wild-type p53 to RGC
      DNA. We show that wild-type T antigen prevents p53 from binding to the RGC site
      under all conditions tested. Moreover, two temperature-sensitive mutant SV40 T
      antigens, which fail to transform cells at the nonpermissive temperature, prevent
      p53 from binding to the RGC site at the permissive, but not at the restrictive,
      temperature. The ability of complexes containing wild-type p53 and tumor-derived
      mutant p53 proteins to bind to RGC DNA varies according to the position of the
      mutation. Complexes containing wild-type and either his175 or his273 mutant p53
      proteins are completely unable to bind to the RGC DNA sequence. Interestingly, a
      complex containing wild-type p53 and the trp248 mutant p53 characteristic of Li
      Fraumeni syndrome patients displays nearly wild-type levels of binding. Perhaps
      this mutant allele can be tolerated in these individuals because the wild-type
      mutant p53 complex maintains the ability to bind to DNA. Our data indicate that
      the oncogenic potential of both T antigen and some mutant p53 proteins is the
      result of their ability to block binding of wild-type p53 to DNA.

PMID- 1398069
TI  - Defects in mRNA 3'-end formation, transcription initiation, and mRNA transport
      associated with the yeast mutation prp20: possible coupling of mRNA processing
      and chromatin structure.
AB  - A temperature-sensitive lethal mutation in Saccharomyces cerevisiae, prp20-1,
      causes defects in several different steps in mRNA metabolism, including mRNA 3'
      end formation, transcription initiation, and mRNA transport. Previous work has
      demonstrated that prp20 mutants are defective in actin pre-mRNA splicing. PRP20
      is related, both in structure and function, to the RCC1 gene of mammals and the
      PIM1 gene of Schizosaccharomyces pombe, both of which appear to regulate entry
      into mitosis and chromosome condensation. In this report we demonstrate that,
      after a shift of prp20 mutants to the restrictive temperature, transcripts of
      several genes (CUP1, CYH2, and GAL10) are produced that extend 1-10 kb beyond
      their normal polyadenylation sites. The failure in 3'-end formation occurs within
      1-2 min of the temperature shift. Transcription initiation also is disrupted, in
      that initiation sites upstream of the normal cap site are used. mRNA transport
      from nucleus to cytoplasm also is perturbed: In situ hybridization using an
      oligo(dT) probe demonstrates accumulation of poly(A) in the nucleus, consistent
      with the accumulation of longer bulk poly(A) (up to approximately 90-100
      nucleotides) and with a failure to transport newly synthesized RNA to the
      cytoplasm. We demonstrate that prp20 and rna1 mutants are very similar, if not
      identical, with respect to each of these biochemical phenotypes. In light of the
      putative role of PRP20 in mitotic control, our results suggest a common step in
      that process and multiple steps in mRNA synthesis and maturation. We speculate
      that the perturbations in mRNA processing are the result of effects on the
      chromatin-nascent RNP-transcription complex or misregulation of a cell cycle
      component that modifies multiple mRNA-processing activities.

PMID- 1398070
TI  - Evidence for instability of mRNAs containing AUUUA motifs mediated through
      translation-dependent assembly of a > 20S degradation complex.
AB  - Many short-lived mRNAs, including those encoding lymphokines, cytokines, and
      proto-oncogenes, contain an AU-rich sequence in their 3'-untranslated regions.
      These AU domains and, more specifically, AUUUA motifs within them, are widely
      thought to mediate the extreme instability of the corresponding mRNAs. This is
      most clearly true for granulocyte monocyte colony stimulating factor (GM-CSF)
      mRNA whose AUUUA motifs are conserved phylogenetically and whose presence in an
      otherwise stable beta-globin mRNA results in a 50-fold decrease in accumulated
      mRNA level. We show that RNA instability conferred by the GM-CSF AU motif
      requires the mRNA to be actively translated and the AU motif to be within the 3'
      untranslated region. By analysis of the sedimentation characteristics, we
      identify a large (> 20S), divalent cation-independent complex found only on
      unstable RNAs. Like instability, complex formation (1) is dependent on
      translation of the RNA, (2) requires intact AUUUA motifs, and (3) is blocked by
      ribosome translocation across the AU-rich motif. We propose that RNA instability
      mediated by the AU motif is achieved through translation-dependent assembly of
      this large mRNA-destabilizing complex.

PMID- 1398071
TI  - A yeast TFIIB-related factor involved in RNA polymerase III transcription.
AB  - A suppressor gene was identified, which in high copy number rescues a temperature
      sensitive mutation in yeast TATA-binding protein (TBP). Suppression was allele
      specific because the suppressor did not rescue the temperature-sensitive
      phenotype of another TBP mutant. This suppressor gene encodes a 596-amino-acid
      protein of which the amino-terminal half is homologous to the Pol II-specific
      factor TFIIB. Disruption of this gene, termed BRF1, showed it to be essential for
      growth of yeast. Deletion of sequences at either the amino or carboxyl terminus
      of BRF1 gave both temperature- and cold-sensitive phenotypes. These temperature-
      and cold-sensitive strains were used to prepare extracts deficient in BRF1
      activity and were tested for transcriptional activity by RNA polymerases I, II,
      and III in vitro. BRF1-deficient extracts are defective in Pol III transcription
      and can be reconstituted for Pol III transcription by the addition of recombinant
      BRF1. Western analysis shows that BRF1 is present in TFIIIB but not the TFIIIC
      fraction, suggesting that it is a component of TFIIIB. We propose that BRF1 plays
      a role in Pol III initiation analogous to the role played by TFIIB for Pol II in
      its interaction with TBP and polymerase. The identification of a Pol III-specific
      TFIIB-like factor extends the previously noted similarity of transcriptional
      initiation by the three nuclear polymerases.

PMID- 1398072
TI  - Multiple domains of the RNA polymerase I activator hUBF interact with the TATA
      binding protein complex hSL1 to mediate transcription.
AB  - Recent evidence suggests that transcription initiation by all three eukaryotic
      RNA polymerases involves a complex of the TATA-binding protein (TBP) and multiple
      TBP-associated factors (TAFs). Here, we map the functional domains of the
      nucleolar HMG box protein hUBF, which binds to the human rRNA promoter and
      stimulates transcription by RNA polymerase I through cooperative interactions
      with a distinct TBP-TAF complex, hSL1. DNase I footprint analysis of mutant hUBF
      proteins and of a synthetic peptide of 84 amino acids reveals that HMG box 1 is
      necessary and sufficient for DNA sequence specificity, whereas other HMG boxes
      and the amino terminus modulate the binding efficiency. hUBF contains multiple
      activation domains that include the acidic carboxyl terminus and three HMG boxes.
      HMG boxes 3 and 4 and the acidic tail contribute significantly to an extended
      footprinting pattern in the presence of hSL1, suggestive of specific protein
      protein interactions. Moreover, the inability of xUBF from Xenopus laevis to form
      an initiation complex with hSL1 can be overcome by hybrid proteins containing
      human HMG box 4 and the acidic carboxyl terminus. These results strongly suggest
      an important role of transcription activation domains of hUBF in mediating
      interactions with the TBP-TAF complex hSL1.

PMID- 1398073
TI  - Holo-TFIID supports transcriptional stimulation by diverse activators and from a
      TATA-less promoter.
AB  - Transcription factor IID (TFIID) binds to TATA boxes, nucleating the assembly of
      initiation complexes containing several general transcription factors and RNA
      polymerase II. Recently, TFIID was shown to be a multisubunit complex containing
      a TATA box-binding polypeptide (TBP) and several tightly associated polypeptides
      (TAFs), which are required for transcriptional stimulation by activator proteins.
      Here, we report the development of a human cell line expressing an epitope-tagged
      TBP and the immunopurification of a native, high-molecular-weight form of TFIID
      that supports transcriptional stimulation by several different classes of
      activation domains. Recovery of basal and activated TFIID transcriptional
      specific activity was close to approximately 100%. Electrophoretic mobility-shift
      analysis demonstrated a single major DNA-protein complex. This holo-TFIID
      contains TAFs of approximately 250, 125, 95, 78, and 50 kD and sediments at 17S.
      Holo-TFIID produced an extended footprint over the adenovirus major late promoter
      TATA box and initiator sequence and supported transcriptional activation from a
      promoter lacking a TATA box. These results lead us to hypothesize that a single
      multisubunit TFIID protein supports transcriptional stimulation by diverse
      activation domains and from a TATA-less promoter.

PMID- 1398074
TI  - Yeast site-specific ribonucleoprotein endoribonuclease MRP contains an RNA
      component homologous to mammalian RNase MRP RNA and essential for cell viability.
AB  - RNase MRP is a site-specific ribonucleoprotein endoribonuclease that cleaves RNA
      sequence complementary to mammalian mitochondrial origins of replication in a
      manner consistent with a role in primer RNA metabolism. The same activity in the
      yeast Saccharomyces cerevisiae has recently been identified; it cleaves an RNA
      substrate complementary to a yeast mitochondrial origin of replication at an
      exact site of linkage of RNA to DNA. We have purified this yeast enzyme further
      and detect a single, novel RNA of 340 nucleotides associated with the enzymatic
      activity. The single-copy nuclear gene for this RNA was sequenced and mapped to
      the right arm of chromosome XIV. The identity of the clone, as encoding the RNA
      copurifying with enzymatic activity, was confirmed by a match to the directly
      determined sequence of the RNA. The gene sequence also identified a 340
      nucleotide RNA in total yeast RNA and in purified RNase MRP enzyme preparations.
      Inspection of the sequence of the yeast RNA revealed homologies to the RNA
      component of mouse RNase MRP, 49% overall with specific regions of much greater
      similarity. The flanking regions of the gene showed characteristics of an RNA
      polymerase II transcription unit, including a TATAAA box and a 7/8 match to the
      yeast cell cycle box UAS. The RNase MRP RNA gene was deleted by insertional
      replacement and found to be essential for cellular viability, indicating a
      critical nuclear role for RNase MRP.

PMID- 1398075
TI  - Protein components specifically associated with prespliceosome and spliceosome
      complexes.
AB  - We have carried out a systematic analysis of the protein composition of highly
      purified mammalian spliceosomes. We show that > 30 distinct proteins, including
      20 previously unidentified components [designated spliceosome-associated proteins
      (SAPs)], are specifically associated with the spliceosome in a salt-resistant
      complex. In contrast to these spliceosome-specific proteins, we show that hnRNP
      proteins are not tightly associated with purified prespliceosome and spliceosome
      complexes. The splicing factor U2AF65, U1 snRNP-specific proteins, and several
      SAPs are present in the earliest prespliceosome complex (E). A set of 10 proteins
      is then added to the first ATP-dependent prespliceosome complex (A), and
      concomitantly, a significant decrease in the level of U2AF65 is observed. The
      fully assembled spliceosome is formed by the addition of 12 proteins in a
      reaction that requires ATP and both the 5' and 3' splice sites.

PMID- 1398076
TI  - The Escherichia coli rna gene encoding RNase I: sequence and unusual promoter
      structure.
AB  - A clone containing the Escherichia coli rna gene encoding the nonspecific
      endoribonuclease, RNase I, was isolated and sequenced. The sequence of the 1070
      nucleotide (nt) fragment agreed completely with that of a rna clone recently
      reported by Meador and Kennell [Gene 95 (1990) 1-7]. The transcription start
      point (tsp) of rna was identified using primer extension analysis, and its
      promoter sequence was established by comparison of RNase I expression levels in
      various deletion mutants. Our results indicate that the rna promoter is highly
      unusual. Its -35 region shows a poor match to the consensus sequence, and
      moreover, it is located within a stem-loop structure that apparently is a Rho
      independent transcription termination site for an upstream gene.

PMID- 1398077
TI  - Sequence analysis of a DNA fragment from Buchnera aphidicola (an endosymbiont of
      aphids) containing genes homologous to dnaG, rpoD, cysE, and secB.
AB  - The aphid, Schizaphis graminum, contains a prokaryotic, obligately intracellular
      endosymbiont, Buchnera aphidicola, which is necessary for the survival of the
      host. A recent study of Bu. aphidicola 16S rRNA has indicated that it is a member
      of the gamma-3 subdivision of the eubacterial class, Proteobacteria, which
      includes Escherichia coli. In order to further characterize the endosymbiont and
      establish its similarity to free-living eubacteria and/or organelles, we have
      cloned and sequenced a 4534-bp DNA fragment containing dnaG-rpoD-cysE-secB. The
      deduced amino acid (aa) sequence identity to the homologous E. coli proteins
      ranged from 47 to 80%. The close proximity of the pair, dnaG-rpoD, to the pair,
      cysE-secB, on the Bu. aphidicola DNA, differed from E. coli, in which these two
      pairs of genes are 14 min apart on the bacterial chromosome. The results of past
      physiological studies of the endosymbiont were consistent with the presence and
      function of DNA primase (DnaG), sigma factor (RpoD) and components of the
      secretory system (SecB). Comparison of the deduced aa sequence of Bu. aphidicola
      CysE (serine acetyltransferase, a key allosterically regulated enzyme in cysteine
      biosynthesis) with the E. coli wild-type enzyme and a mutant defective in
      feedback inhibition suggested that the endosymbiont CysE may not be regulated. By
      analogy with E. coli, the lack of feedback inhibition may lead to overproduction
      of cysteine by the endosymbiont. The results of this and previous investigations
      indicate that Bu. aphidicola has many of the properties of free-living bacteria
      and not of organelles.

PMID- 1398078
TI  - Production of an enzymatically inactive analog of phospholipase D from
      Corynebacterium pseudotuberculosis.
AB  - The gene pld, encoding the phospholipase D (PLD) of Corynebacterium
      pseudotuberculosis, was mutagenized using formic acid and then expressed in
      Escherichia coli. Mutagenesis was targeted at the coding region of pld, so as to
      produce only one or a limited number of point mutations. Transformants were
      screened for the enzymatic and immunological properties of their PLD products.
      One clone was found to produce a protein which was enzymatically inactive, but
      which was comparable to the wild-type PLD in size and antigenicity. The sequence
      of the pld mutant revealed a single base change. As a consequence, the codon for
      His20 was converted to Tyr. These results suggest that His20 forms part of the
      active site of the PLD molecule. If this protein is immunogenic in sheep, it
      would form the basis of a genetically inactivated vaccine.

PMID- 1398080
TI  - Genetic transformation of a halophilic archaebacterium with a gas vesicle gene
      cluster restores its ability to float.
AB  - The halophilic archaebacterium, Halobacterium halobium, and many other aquatic
      bacteria synthesize gas-filled vesicles for flotation. We recently identified a
      cluster of 13 genes (gvpMLKJIHGFEDACN) on a 200-kb H. halobium plasmid, pNRC100,
      involved in gas vesicle synthesis. We have cloned and reconstructed the gvp gene
      cluster on an H. halobium-E. coli shuttle plasmid. Transformation of H. halobium
      Vac- mutants lacking the entire gas vesicle gene region with the gvp gene cluster
      results in restoration of their ability to float. These results open the way
      toward further genetic analysis of gas vesicle gene functions and directed
      flotation of other microorganisms with potential biotechnological applications.

PMID- 1398079
TI  - Isolation and complete sequence of the purL gene encoding FGAM synthase II in
      Lactobacillus casei.
AB  - The purL gene from Lactobacillus casei, encoding
      phosphoribosylformylglycinamidine synthase II involved in the de novo synthesis
      of purines, was cloned and sequenced. The putative purL product of 741 amino
      acids (M(r) of 79,575) shows 25% and 53% identity to the homologous enzymes from
      Escherichia coli and Bacillus subtilis, respectively. In addition, partial
      sequences of two other pur genes (purQ and purF) and a possible third gene (purC)
      were obtained. All these genes are organized in an operon similar to that of B.
      subtilis. In contrast, the corresponding genes from E. coli and Salmonella
      typhimurium are scattered through the genome.

PMID- 1398081
TI  - pYLZ vectors: Saccharomyces cerevisiae/Escherichia coli shuttle plasmids to
      analyze yeast promoters.
AB  - Two yeast/Escherichia coli shuttle vectors have been constructed to analyze
      promoter structures in Saccharomyces cerevisiae: the multicopy vector, pYLZ-2,
      and the centromere-based vector, pYLZ-6. Both plasmids contain the coding region
      of lacZ from E. coli lacking the N-terminal eight amino acids. The truncated
      reporter gene is preceded by a short polylinker (MCS) suitable for the insertion
      of promoter fragments. The vectors allow for the study of expression from
      complete promoters containing UAS and TATA elements, transcriptional start
      point(s) and the original context of the ATG start codon of a yeast gene. A yeast
      terminator fragment has been inserted 3' of the lacZ coding region. It contains
      the transcription termination region of the convergently transcribed yeast genes,
      GCY1 and PFY1, together with sequences corresponding to the mapped 3'-ends of the
      respective mRNAs. As an example, reporter activity was measured with promoter
      fragments from three yeast genes (GCY1, PFY1 and LEO1). The results demonstrate
      the efficiency of the plasmids for studying constitutive and regulated
      transcription, both at high and low levels of expression.

PMID- 1398082
TI  - Sequence of the subtilisin-encoding gene from an antarctic psychrotroph Bacillus
      TA41.
AB  - The nucleotide sequence of the subtilisin-encoding gene from the antarctic
      psychrotroph, Bacillus TA41, was determined. The primary structure of the
      subtilisin precursor corresponds to a preproenzyme of 419 amino acids. Asp144,
      His181 and Ser359 are the proposed catalytic residues of the protease active
      site.

PMID- 1398083
TI  - Sequence encoding ribosomal protein L33 of Lactococcus lactis.
AB  - A cloned fragment from Lactococcus lactis chromosome encoding the L33 ribosomal
      protein was sequenced. Two incomplete open reading frames (ORFs) were also found:
      the upstream ORF shows similarity to the tetracycline-resistance protein (Tet) of
      Bacillus stearothermophilus, and the downstream ORF shows homology to a protein
      of Bacillus subtilis participating in sporulation (SpoVE), and to proteins of
      Escherichia coli involved in cell division (FtsW) and the maintenance of cell
      shape (RodA).

PMID- 1398084
TI  - Cloning and sequencing of the gene encoding a ribonuclease from Streptomyces
      aureofaciens CCM3239.
AB  - A ribonuclease-encoding gene (rnaSa3) from Streptomyces aureofaciens CCM3239 has
      been isolated and sequenced. The deduced amino acid sequence shows 77% homology
      with RNase Sa from S. aureofaciens.

PMID- 1398085
TI  - Vectors for generating nested deletions and facilitating subcloning G+C-rich DNA
      between Escherichia coli and Streptomyces sp.
AB  - New multiple cloning sites (MCS), which facilitate the subcloning of G+C-rich
      DNA, were added to pUC18, M13mp18, pVE616 (a pBR322-derived insertion vector),
      and the low-copy-number Streptomyces vector, pIJ922. The MCS in these vectors
      contain sites found infrequently in Streptomyces DNA, facilitating the exchange
      of subclones between the vectors. The MCS added to M13mp18 and pUC18 was also
      designed to generate nested deletions within subcloned fragments.

PMID- 1398086
TI  - Sequence of the 5-aminolevulinic acid dehydratase-encoding gene from the
      hyperthermophilic methanogen, Methanothermus sociabilis.
AB  - We report on the sequence of the Methanothermus sociabilis aladh gene, which
      encodes the 5'-aminolevulinic acid dehydratase. The identity of the enzyme was
      determined by sequence comparison and by expression in Escherichia coli.

PMID- 1398087
TI  - Sequence analysis of a gene cluster encoding cellulases from Clostridium
      cellulolyticum.
AB  - The sequence of a 5633-bp EcoRI-PvuII DNA fragment from Clostridium
      cellulolyticum was determined. This fragment contains two complete endo-beta-1,4
      glucanase-encoding genes, designated celCCC and celCCG. These two genes are
      flanked by two other partial open reading frames (ORF1 and celCCE) that probably
      encode two cellulases or related enzymes. The celCCC and celCCG genes appear to
      be present in a polycistronic transcriptional unit. Northern blot hybridisations
      with intragenic probes derived from celCCC and celCCG gave similar patterns. Two
      transcripts of about 5 and 6 kb were identified. The celCCC and celCCG ORFs
      extend over 1380 bp and 2175 bp, respectively. They are separated by only 87 nt.
      A typical signal sequence is present at the N terminus of the deduced
      polypeptides. The mature CelCCC and CelCCG proteins have M(r)s 47,201 and 76,101,
      respectively. Comparisons between their amino acid (aa) sequences and other known
      cellulase sequences revealed that: first, they both contain the repeated 24-aa
      sequence characteristic of clostridial beta-glycanases, secondly, the N-terminal
      catalytic domains of CelCCC and CelCCG can be classified into the D and E2
      families, respectively, and thirdly, the largest CelCCG contains an additional
      internal domain which is very similar to that of the Bacillus-type cellulose
      binding domain (CBD). The ORF1-C-terminal-encoded sequence also contains the
      clostridial 24-aa repeat. The CelCCE N-terminus consists of a typical signal
      sequence followed by a 168-aa domain homologous to the N-terminal repeated domain
      of Cellulomonas fimi CenC. This domain is connected to an incomplete catalytic
      domain of family E1 by a Pro-rich junction linker.

PMID- 1398088
TI  - Cloning and sequencing of the aculeacin A acylase-encoding gene from Actinoplanes
      utahensis and expression in Streptomyces lividans.
AB  - Aculeacin A acylase (AAC), produced by Actinoplanes utahensis, catalyzes the
      hydrolysis of the palmitoyl moiety of the antifungal antibiotic, aculeacin A.
      Using mixed oligodeoxyribonucleotide probes based on the N-terminal amino acid
      (aa) sequences of the two subunits of AAC, overlapping clones were identified in
      a cosmid library of A. utahensis DNA. After the sub-cloning of a 3.0-kb fragment
      into Streptomyces lividans, the recombinant produced AAC extracellularly. The
      nucleotide sequence of this fragment predicted an open reading frame of 2358 bp
      with GTG start and TGA stop codons. The deduced 786-aa sequence should correspond
      to a single polypeptide chain, indicating that this polypeptide is processed to
      the active form which is composed of the two subunits. Threefold more AAC was
      obtained from the S. lividans recombinant carrying the cloned gene than the
      original A. utahensis strain.

PMID- 1398090
TI  - A multisite integrative cassette for the yeast Saccharomyces cerevisiae.
AB  - We have developed a cassette for the integration of cloned DNA sequences at
      multiple sites in the Saccharomyces cerevisiae genome, taking advantage of the
      naturally repeated sigma sequences. This cassette contains one engineered sigma
      element which allows the targeting of an embedded gene at different genomic sigma
      elements by gene replacement. Two yeast genes, ARG4 and URA3, were thus
      integrated in the absence of any bacterial sequences, individually or
      sequentially on twelve chromosomes. Consequently, these studies led to the
      genetical tagging of individual members of the sigma family.

PMID- 1398089
TI  - Bending-incompetent variants of Flp recombinase mediate strand transfer in half
      site recombinations: role of DNA bending in recombination.
AB  - One key feature of the interaction of Flp recombinase with its target site (FRT)
      is the large bend introduced in the substrate as a result of protein binding. The
      extent of bending was found to depend on the phasing and spacing of the Flp
      monomers occupying the two Flp-binding elements (FBE) bordering the strand
      exchange region (spacer) of the substrate. The relative mobilities of the Flp
      complexes formed by the two permuted substrate fragments, containing the FRT site
      near the end or in the middle, corresponded to a DNA bend of approx. 140 degrees
      when each of the two FBEs flanking the spacer was occupied by a protein monomer.
      The estimated bend angle was the same when the reference DNA fragment with the
      FRT site at the end was substituted by one with the site in the middle, but
      containing a 4-bp insertion within the spacer. We used a combination of wild-type
      Flp and Flp variants that were competent or incompetent in DNA bending, together
      with full, or half FRT sites, to ask whether bending is a conformational
      requirement for catalysis, namely cleavage and exchange of strands. We obtained
      the following results: in full-site (FRT) vs. full-site recombinations or in full
      site vs. half-site (half FRT) recombinations, there was a large difference in the
      reactivity between Flp and a bending-incompetent Flp variant. This difference
      virtually disappeared when reactions were done with half-FRT sites. We conclude
      that bending is not a prerequisite for catalysis, but represents the manner in
      which the substrate accommodates the Flp protomer-protomer interactions that are
      pertinent to catalysis.

PMID- 1398091
TI  - Characterization of the tRNA(Trp) genes of Saccharomyces cerevisiae.
AB  - The purpose of this work was to examine the tRNA(Trp)-encoding genes (tRNA(Trp))
      of Saccharomyces cerevisiae to gain insight as to why tRNA(Trp) amber
      suppressors, isolated by conventional genetic techniques, have not been reported.
      The results herein indicate that the haploid yeast genome contains six tRNA(Trp)
      genes which map to five or six chromosomes. Not only do the six genes have
      identical coding sequences but their introns are also identical. Gene replacement
      experiments indicate that five copies of tRNA(Trp) are sufficient for cell
      viability. Thus, mutation of one tRNA(Trp) gene to a suppressor in vivo, lowering
      the functional number of tRNA(Trp) genes, would not be expected to be lethal.

PMID- 1398092
TI  - Kluyveromyces lactis rDNA as a target for multiple integration by homologous
      recombination.
AB  - Gene targeting to a single chromosomal locus has been extensively used in
      Saccharomyces cerevisiae. In this study, we have analyzed targeting of a
      repetitive sequence, the 25S rDNA gene, to the chromosomal rDNA cluster of
      Kluyveromyces lactis by the use of a replacement vector. We have obtained K.
      lactis transformants carrying multiple copies of the replacement cassette
      inserted into the rDNA chromosomal locus. Analysis of several transformants has
      shown that the number of integrated copies could range from 4 to 40. Moreover,
      the distribution of integration sites within the rDNA locus was found to differ
      in most transformants. Single-copy integration at multiple sites, rather than
      multicopy integration at a very limited number of sites, was found to be the most
      frequent event. Also, in most transformants, integration sites were distributed
      at random as well as in an orderly fashion, i.e., in contiguous or alternate rDNA
      repeats, suggesting that amplification of the integrated sequences, rather than
      multiple integration events, may account for the copy number of insertions.

PMID- 1398093
TI  - Isolation and characterization of the Schizosaccharomyces pombe rad3 gene,
      involved in the DNA damage and DNA synthesis checkpoints.
AB  - We have cloned the Schizosaccharomyces pombe rad3 gene which is involved in G2
      arrest following DNA damage, and in the dependence of mitosis on the completion
      of DNA replication. The gene was cloned by complementation of the sensitivity to
      UV light and gamma rays of the rad3-136 mutant with an Sz. pombe genomic library.
      Sublocalization of the complementing activity and sequencing of the clone
      identified an intronless 3210-bp open reading frame capable of encoding a 1070
      amino acid protein with an M(r) of 121974. The rad3 gene is a new gene with no
      homologs in existing sequence databases. The gene is poorly expressed, with a
      codon bias index of -0.01. A disruption mutant affecting the coding region was
      only slightly more sensitive to UV light than the original rad3-136 mutant. The
      rad3 gene was mapped to NotI fragment C on chromosome II.

PMID- 1398094
TI  - Stable incorporation of genetic material into the chromosome of Rhizobium
      meliloti 41: construction of an integrative vector system.
AB  - An integrative vector system has been developed from the site-specific
      recombination elements of temperate phage 16-3. The system can be used for highly
      efficient stable introduction of genetic material into the chromosome of the
      symbiotic nitrogen-fixing organism, Rhizobium meliloti 41 (Rm41) at the attB
      site. Vectors carrying the phage-borne attachment site were constructed, and
      helper phages providing the site-specific recombination functions in trans were
      isolated. Other possible applications of the system are discussed.

PMID- 1398095
TI  - Stabilization of T7-promoter-based pARHS expression vectors using the parB locus.
AB  - We describe a modification of the pAR3040 vector which results in its efficient
      stabilization during cell division. The parB locus of the plasmid R1 was
      introduced into the plasmid, pAR3040, to construct the pARHS vectors. These
      vectors are stable for at least 60 cell generations, even in the absence of
      selection by an antibiotic present in the culture media, both with or without
      IPTG induction.

PMID- 1398096
TI  - Characterization of the rRNA-encoding genes and transcripts, and a group-I self
      splicing intron in Pneumocystis carinii.
AB  - Although Pneumocystis carinii is the most common opportunistic pathogen infecting
      individuals with AIDS, very little is known of the basic biology of the organism.
      We have examined the ribosomal RNA (rRNA) and the DNA encoding it (rDNA) in P.
      carinii in an attempt to clarify its taxonomic position and to begin to study its
      genetic processes. Electrophoretic analysis showed that the sizes of the P.
      carinii rRNAs are quite similar to the sizes of the corresponding rRNAs from
      Saccharomyces cerevisiae. Direct sequence analysis of approx. 60% of the 18S
      small subunit-rRNA (Ss-rRNA) confirmed that its sequence is similar to that of
      yeast-like fungi and that a putative group-I intron previously observed in the
      18S rDNA is, in fact, excised from the mature rRNA. PCR analysis of the intron in
      P. carinii genomic DNA showed that each of the multiple rDNA genes bears the
      group-I intron and in vitro transcripts of the intron autocatalytically excise
      from the rRNA primary transcript in the presence of GTP. Finally, analogues of
      GTP inhibit the self-splicing reaction, indicating that the guanosine-binding
      site of the intron closely resembles that of other well-characterized group-I
      introns. Since no group-I introns have been found in higher eukaryotes, this self
      splicing process represents a viable target for chemotherapy of P. carinii
      pneumonia (PCP).

PMID- 1398097
TI  - Cloning, sequence and expression of a beta-tubulin-encoding gene in the
      homobasidiomycete Schizophyllum commune.
AB  - The beta-tubulin (beta Tub)-encoding gene (tub-2) of Schizophyllum commune is the
      first tubulin gene isolated, cloned and sequenced from higher filamentous fungi
      (homobasidiomycetes). The S. commune tub-2 gene is organized into nine exons and
      eight introns. The introns vary from 48 to 107 nt in length, and are distributed
      throughout the gene. The tub-2 exons code for a protein of 445 amino acids (aa),
      which shows great homology with beta Tubs of filamentous ascomycetes, plants, and
      animals, but less homology with yeasts. The codon usage of tub-2 from S. commune
      is biased, as it is in most beta Tub-encoding genes of filamentous fungi. The S.
      commune beta Tub shows a conserved aa sequence in the C-terminal domain, which is
      suggested to interact with microtubule-associated proteins in animals. In
      contrast, the S. commune beta Tub deviates from most known beta Tubs by having a
      Cys165 residue, which might be significant for the insensitivity of S. commune
      haploid strains to the antimicrotubule drug, benomyl. In tub-2 of different
      haploid strains, sequence polymorphisms occur in the 5' and 3' flanking regions.
      The expression of tub-2 is high in young mycelium, which has a high number of
      extending apical cells, but decreases with the aging of the mycelium. No
      significant difference in the hybridization signal intensity for the tub-2
      transcripts was recorded either during intercellular nuclear migration at early
      mating, or in mycelia with a mutation in the B mating-type gene.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1398098
TI  - Isolation and characterization of a cellulose-growth-specific gene from Agaricus
      bisporus.
AB  - The edible basidiomycete, Agaricus bisporus, produces extracellular
      endoglucanase. Endoglucanase production is induced by cellulose and repressed by
      fructose in A. bisporus grown on minimal medium, and is regulated in activity
      during fruiting body development. An anti-endoglucanase antibody was used to
      isolate cellulase-related genes. Three main polypeptides of 38, 58, and 60 kDa
      were immunoprecipitated by the antibody from products of in vitro cell-free
      translation of mRNAs isolated from cellulose-grown mycelium. No cross-reaction
      was detected with the translated products from fructose-grown mycelium. This
      antibody was used to immunoscreen a lambda ZAPII-cDNA expression library made
      from mRNA isolated from cellulose-grown mycelium. Two cDNA cross-reacting clones,
      pSRc110 and pSRc200, were isolated. Clones pSRc110 and pSRc200 cross-hybridized
      and had the same restriction map. Clone pSRc200 hybrid selected an mRNA that on
      cell-free translation produced a 38-kDa polypeptide. The cDNA fragment from
      pSRc200 hybridized to a 1.3-kb mRNA from cellulose-grown mycelium. No
      hybridization was observed when using fructose-grown mycelium mRNA. Thus, the
      gene (cel1) expressing the 1.3-kb mRNA, is differentially regulated by the carbon
      source of the culture medium. The cell gene was isolated in a 8.9-kb EcoRI
      genomic fragment after hybridization to pSRc200. Sequences similar to those in
      the egl1 and cbh2 genes from Trichoderma reesi were found upstream from the ATG
      start codon in cel1. Nine short intervening sequences disrupt the cel1 coding
      sequence, and a strong bias against codons ending with G and A was
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398099
TI  - Primary structure of a gene-sized DNA encoding calmodulin from the hypotrichous
      ciliate Stylonychia lemnae.
AB  - We have isolated and characterized a gene-sized DNA encoding calmodulin (Clm)
      from macronuclear (MA) DNA of the hypotrichous ciliate, Stylonychia lemnae. The
      gene has 3500 copies per macronucleus. The length of the gene was deduced by
      agarose-gel electrophoresis of MA DNA and Southern blot analysis using a Clm cDNA
      probe from chicken. We then isolated the gene from a MA library. The overall
      length of the gene is 821 bp with a 450-bp intronless coding region. The deduced
      amino acid (aa) sequence of ciliate Clm has 149 aa and an M(r) of 16,819. Both
      ends of the cloned gene have the hypotrichous telomeric C4A4 repeat. The coding
      region is flanked by a 158-bp 5'-leader sequence and a 3'-trailer sequence of 213
      bp. S1 analysis was used to locate the transcription start point (tsp) 49 bp
      upstream from the start codon. No common eukaryotic transcription signals were
      found upstream from the tsp. A second gene-sized DNA, detected by its cross
      hybridization with the Clm DNA, predicts the existence of a second Ca(2+)-binding
      protein with only one Ca(2+)-binding site. It's function and biological
      significance is yet unknown.

PMID- 1398100
TI  - Expression of a downstream gene from a bicistronic transcription unit in
      transgenic tobacco plants.
AB  - We have constructed a set of plasmids carrying an artificial compact stop-start
      codon sequence, TGATGTAACATGA, between an upstream open reading frame,
      terminating at one of the stop codons, and a downstream kanamycin-resistance
      (KmR)-encoding gene (nptII) initiating at the second ATG. These plasmids were
      introduced into tobacco protoplasts by direct gene transfer. The efficiency of
      expression of the downstream nptII gene was measured by scoring the number of KmR
      transformants. With a closer distance between the functional stop and start
      codons, a tendency to less efficient expression of nptII was found. The
      integration and expression of both genes as a bicistronic transcription unit were
      verified by Southern- and Northern-blot analyses. A possible application of the
      compact stop-start codon sequence for insertional mutagenesis is discussed.

PMID- 1398101
TI  - Compositional bimodality and evolution of retroviral genomes.
AB  - The compositional distributions of genomes, genes (and their third codon
      positions) and long terminal repeats from retroviruses of warm-blooded
      vertebrates are characterized by a striking bimodality which is accompanied by a
      remarkable compositional homogeneity within each retroviral genome. A first,
      major class of retroviral genomes is GC-rich, whereas a second, minor class is GC
      poor. Representative expressed viral genomes from the two classes integrate in GC
      rich and GC-poor isochores, respectively, of host genomes. The first class
      comprises all oncoviruses (except B-types and some D-types), the second,
      lentiviruses, spumaviruses, as well as B-type and some D-type oncoviruses (e.g.,
      mouse mammary tumor virus and simian retroviruses type D, respectively). The
      compositional bimodal distribution of retroviral genomes and the accompanying
      compositional homogeneity within each retroviral genome appear to be the result
      of the compositional evolution of retroviral genomes in their integrated form.

PMID- 1398102
TI  - The structure and complete sequence of the gene encoding chicken ribosomal
      protein L5.
AB  - The nucleotide (nt) sequence of the gene encoding chicken ribosomal protein L5,
      which associates with 5S rRNA, was determined. The gene contains eight exons and
      seven introns which spread over 7252 bp. The transcription start point (tsp) is a
      C residue in a tract of 13 pyrimidines, and its 5'-flanking region lacks
      canonical TATA and CAAT boxes. The G+C content of the region around the tsp is
      calculated as high as 78%, and nine GC boxes exist within the 5'-flanking region
      and the first intron. The nt sequence at positions -36 to -22 is similar to an
      internal sequence at positions 56-70 of the gene encoding chicken 5S rRNA, which
      corresponds to the transcriptional internal control region of the 5S rRNA
      encoding gene of Xenopus laevis. This region might contribute to the coordinate
      expression of the genes encoding protein L5 and 5S rRNA.

PMID- 1398103
TI  - Cloning and expression analysis of two ZFY-related zinc finger genes from
      Alligator mississippiensis, a species with temperature-dependent sex
      determination.
AB  - In order to investigate the molecular mechanism of temperature-dependent sex
      determination, a human zinc finger gene (ZFY), known to be highly conserved
      amongst other species, was used to isolate homologues from the genome of the
      American alligator, Alligator mississippiensis. ZFY was originally a candidate
      for the primary testis-determining gene in man, but is now thought to function
      further down the sex-determining cascade. Two alligator genes are described, Zfc
      and Znc6. Both code for zinc finger proteins and exhibit amino acid (aa)
      homologies to ZFY of 91% and 73%, respectively. Znc6 shows aa homology of 88% to
      the protein encoded by the zinc finger exon of the human ZFY-related gene, ZNF6,
      recently found on the X chromosome. Analysis of Zfc and Znc6 expression during
      embryonic development identified two major transcripts of 5.9 kb and 2.7 kb
      coding for Zfc, whilst only one transcript of 4.8 kb was detected for Znc6. Both
      genes are transcribed at all stages tested, from day 3 (post egg laying)
      throughout gestation. The expression level of all transcripts appears to decline
      towards the time of hatching (65-72 days). No sex-specific differences in the
      expression were observed. The extensive sequence conservation of the genes
      between reptiles and humans suggests major functional constraints. The expression
      patterns indicate that these genes do not play a primary role in temperature
      dependent sex determination.

PMID- 1398104
TI  - A protein binding to CArG box motifs and to single-stranded DNA functions as a
      transcriptional repressor.
AB  - A CArG box motif [CC(A+T-rich)6GG] is one of the DNA elements required for muscle
      specific gene transcription. Nuclear factors in mouse C2 myogenic cells strongly
      bind to the CArG box in the first intron of the gene (Sm alpha-A) encoding human
      smooth muscle alpha-actin. To clone cDNAs of the CArG box-binding factor (CBF),
      lambda gt11 cDNA expression libraries from C2 cells were screened for in situ DNA
      binding specific for this CArG box sequence. The 1.6-kb cDNA (CBF-A) encoding 285
      amino acids (aa) was obtained, and a beta-galactosidase fusion protein,
      bacterially produced from the cDNA, bound to DNA fragments containing several
      CArG boxes. When the expression level of CBF-A in C2 cells increased by
      transfection of CBF-A expression plasmids, Sm alpha-A transcription was
      repressed. The deduced aa sequence of CBF-A is similar to some single-stranded
      (ss) nucleic acid-binding proteins. The fusion protein could bind to ssDNA,
      whereas CBF in C2 cell nuclear extracts could not. From these results, CBF-A is a
      novel CArG box-, ssDNA- and RNA-binding protein, as well as a repressive
      transcriptional factor.

PMID- 1398105
TI  - Functional analysis of the human estrogen receptor using a phenotypic
      transactivation assay in yeast.
AB  - We have constructed yeast strains in which the expression of the Saccharomyces
      cerevisiae URA3 gene is induced by the human estrogen receptor (hER). Promoter
      sequences required for both basal and activated transcription of URA3 were
      replaced with one or three estrogen-response elements (EREs) positioned upstream
      of the native TATA box. These constructs were each integrated at the TRP1 locus
      of a yeast strain in which the natural URA3 gene had been deleted, and the
      integrants were transformed with low- or high-copy-number shuttle plasmids
      expressing wild-type or truncated derivatives of hER. Transformants were assayed
      for growth on uracil-deficient medium plus or minus estradiol (E2), for
      resistance to 5-fluoroorotic acid (5-FOA) and for activity of OMPdecase
      (orotidine-5'-monophosphate decarboxylase), the product of the URA3 gene. We show
      that the growth and 5-FOA-resistance (5-FOAR) phenotypes of these strains are
      strictly dependent upon the function of the receptor derivatives. Induction of
      URA3, measured by OMPdecase activity, was observed over a 20- to 2500-fold range
      depending on the receptor derivative, its expression level and the number of EREs
      in the responsive promoter. Both one- and three-ERE reporter strains expressing
      the full-length receptor are completely E2-dependent for growth, and display a 5
      FOAR phenotype in the absence of the hormone. We demonstrate that the individual
      hER transactivation functions, TAF1 and TAF2, are both functional in yeast, and
      that the hormone-dependent TAF2 is the more potent activator on our reporters. We
      show that hER displays strong homosynergism in yeast, and discuss the
      contributions of the two TAFs in hER synergism.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398106
TI  - Cleavage and recognition pattern of a double-strand-specific endonuclease (I
      creI) encoded by the chloroplast 23S rRNA intron of Chlamydomonas reinhardtii.
AB  - Several group-I introns have been shown to specifically invade intron-minus
      alleles of the genes that contain them. This type of intron mobility is referred
      to as 'intron homing', and depends on restriction endonucleases (ENases) encoded
      by the mobile introns. The ENase cleaves the intron-minus allele near the site of
      intron insertion, thereby initiating gene conversion. The 23S (LSU) rRNA-encoding
      gene (LSU) of the chloroplast genome of Chlamydomonas reinhardtii contains a self
      splicing group-I intron (CrLSU) that has a free-standing open reading frame (ORF)
      of 163 codons. Translation of CrLSU intron RNA in cell-free systems produces a
      polypeptide of approx. 18 kDa, the size expected for correct translation of the
      ORF. The in vitro-synthesized 18-kDa protein cleaves plasmid DNA that contains a
      portion of LSU where the intron normally resides, but lacking the intron itself.
      Cleavage by the intron-encoded enzyme (I-CreI) occurs 5 bp and 1 bp 3' to the
      intron insertion site (in the 3'-exon) in the top (/) and bottom (,) strands,
      respectively, resulting in 4-nt single-stranded overhangs with 3'-OH termini. We
      also show that the recognition sequence of I-CreI spans the cleavage site and is
      24 bp in length (5'-CAAAACGTC,GTGA/GACAGTTTGGT).

PMID- 1398107
TI  - Amplification and characterization of an inverted repeat from the Chlamydomonas
      reinhardtii mitochondrial genome.
AB  - Based on the nucleotide (nt) sequences of cob and L2a, two
      oligodeoxyribonucleotides (oligos) were synthesized and used in the polymerase
      chain reaction (PCR) to amplify the termini of the Chlamydomonas reinhardtii
      mitochondrial (mt) genome. A 0.8-kb PCR product was detected by agarose-gel
      electrophoresis when using unligated mt DNA as the template for PCR. This may
      have indicated the presence of a naturally occurring circular mt DNA molecule
      that acted as the PCR template. The 0.8-kb DNA could also be amplified from the
      linear mt DNA via an intramolecular jump during PCR. The sequence data from the
      0.8-kb PCR product, and the right 0.6-kb and left 1-kb terminal fragments of the
      linear mt DNA, along with Southern hybridization analysis, indicated that a 0.49
      kb inverted repeat (IR) sequence is present at the right and left termini of the
      linear mt DNA. The IR contains A+T-rich clusters, as well as numerous short
      direct repeats (DR) and IR, and might be involved in the recombination,
      replication and expression of the C. reinhardtii mt genome.

PMID- 1398108
TI  - Myristoylation-dependent membrane targeting and release of the HTLV-I Gag
      precursor, Pr53gag, in yeast.
AB  - The unprocessed HTLV-I Gag precursor, Pr53gag, was synthesized in yeast,
      Saccharomyces cerevisiae. The synthesized Pr53gag was myristoylated, associated
      with the cellular membrane, and released into the culture medium. The released
      Pr53gag was pelleted by centrifugation at 100,000 x g for 2 h. Conversion of Gly2
      to Ala allowed synthesis of a non-myristoylated soluble Pr53gag which was not
      released into the culture medium. These results suggest that the release of the
      HTLV-I Gag precursors Pr53gag, occurs in yeast in a myristoylation-dependent
      manner.

PMID- 1398110
TI  - The pyrimidine sequence encompassing the transcription start point of Xenopus
      laevis ribosomal-protein-encoding genes is not obligatory for activity in
      oocytes.
AB  - The genes coding for ribosomal proteins (r-proteins) in Xenopus laevis have a
      stretch of about 20 pyrimidines (Y) at their 5' end, in the middle of which is
      localized the main transcription start point (tsp). To obtain information about
      its possible functional significance, we have introduced by site-directed
      mutagenesis one or more purines at various positions within the oligo(Y) tract
      present at the 5' end of the gene coding for r-protein S19 of X. laevis. The
      effect of these mutations on transcription and translation of a reporter-coding
      sequence has been evaluated by DNA microinjection in X. laevis oocytes. We show
      that an uninterrupted stretch of pyrimidines is not necessary for efficient
      transcription and translation of the reporter gene in the X. laevis oocyte. This
      finding does not exclude the possibility that this sequence is involved in
      transcription and/or translation regulation in some developmental situations
      different from oogenesis.

PMID- 1398109
TI  - Four synonymous genes encode calmodulin in the teleost fish, medaka (Oryzias
      latipes): conservation of the multigene one-protein principle.
AB  - We cloned four distinct calmodulin (CaM)-encoding cDNAs from a small teleost
      fish, medaka (Oryzias latipes). The deduced amino acid (aa) sequences were
      exactly the same in these four genes and identical to the aa sequence of
      mammalian CaM, because of synonymous codon usages. The four cDNAs from medaka,
      termed CaM-A, -B, -C and -D, corresponded to mRNAs of 1.8, 1.4, 2.5 and 1.8 kb,
      respectively, in Northern blot analysis. Our results demonstrated that the
      'multigene one-protein' principle of CaM synthesis is applicable to medaka, as
      well as to mammals whose CaM is encoded by at least three different genes.

PMID- 1398111
TI  - Isolation and characterization of the mouse alpha-lactalbumin-encoding gene:
      interspecies comparison, tissue- and stage-specific expression.
AB  - The murine alpha-lactalbumin-encoding gene (m alpha La) was isolated and
      completely sequenced. The 2.3-kb transcription unit shared a similar organization
      with that of its counterparts from other species. Sequence comparison for the
      proximal 5'-flanking region indicated the presence of a consensus motif that
      occurs in all milk-protein-encoding genes, except the kappa-casein-encoding gene.
      This may correspond to the binding site for the recently identified mammary-gland
      specific factor. The m alpha La gene occurs in a single copy per haploid genome
      and is specifically expressed in the mammary gland where it is induced during
      late pregnancy.

PMID- 1398112
TI  - A silencer-like cis element for the testis-specific phosphoglycerate-kinase-2
      encoding gene.
AB  - Phosphoglycerate kinase (PGK), a glycolytic enzyme, possesses two isozymes:
      somatic-type PGK-1 and testis-specific PGK-2, encoded by distinct genes. Tissue
      specific expression of the two PGK-encoding genes (Pgk) seems to be
      transcriptionally controlled, since tissue distribution of the mRNAs coincides
      well with that of the proteins. In the present study, we determined the cis
      acting DNA elements that regulate the transcription of mouse Pgk-2. A transient
      expression assay of DNAs having various portions of the Pgk-2 upstream region
      linked to the chloramphenicol acetyltransferase (CAT)-encoding gene (cat) was
      performed using mouse cell lines that exclusively express Pgk-1. A substantial
      increase in cat expression was observed when the region between nucleotides (nt) 
      1404 and -685, relative to the most distal transcription start point at nt +1,
      was lost. This cis-acting region appeared to function as a silencer, since it
      repressed cat expression independently of either orientation to or distance from
      the Pgk-2 promoter. Moreover, the cis element inhibited Pgk-2 transcription with
      no effect on Pgk-1 transcription in a cell-free system using nuclear extracts of
      rat liver. These results suggest that a silencer-like negative cis element is
      responsible, at least partly, for tissue-specific transcription of Pgk-2.

PMID- 1398113
TI  - Human ribosomal protein S3a: cloning of the cDNA and primary structure of the
      protein.
AB  - The amino acid (aa) sequence of human ribosomal protein S3a (hRPS3a) was deduced
      partially from the nucleotide sequence of the corresponding cDNA and confirmed by
      direct aa sequencing from the N terminus of the purified hRPS3a protein. The cDNA
      clone was isolated from a cDNA expression library in the pEX vector using
      antibodies. The hRPS3a protein has 263 aa and its calculated M(r) is 29 813.

PMID- 1398114
TI  - Cloning and chromosomal mapping of nuclear genes encoding chloroplast and
      cytosolic glyceraldehyde-3-phosphate-dehydrogenase from Arabidopsis thaliana.

PMID- 1398115
TI  - Sequence of the vanY gene required for production of a vancomycin-inducible D,D
      carboxypeptidase in Enterococcus faecium BM4147.
AB  - Cloning and nucleotide sequencing identified the vanY gene as a member of the
      vancomycin-resistance van gene cluster of enterococcal plasmid, pIP816. The vanY
      gene was necessary for synthesis of the vancomycin-inducible D,D-carboxypeptidase
      activity previously proposed to be responsible for glycopeptide resistance.
      However, this activity was not required for peptidoglycan synthesis in the
      presence of glycopeptides. The deduced product of vanY did not display
      significant similarity with other D,D-carboxypeptidases.

PMID- 1398117
TI  - Cloning and regulatory analysis of starvation-stress gene, ssgA, encoding a
      hydrophobin-like protein from the entomopathogenic fungus, Metarhizium
      anisopliae.
AB  - The nucleotide (nt) sequence of a starvation-stress gene (ssgA) of the
      entomopathogenic fungus, Metarhizium anisopliae, and its deduced amino acid (aa)
      sequence were determined. The primary structure of the SSGA (96 aa; deduced M(r)
      = 9925; pI = 4.1) protein shares extensive similarities with fungal wall proteins
      of the 'hydrophobin' class, and the eight Cys residues and putative signal
      sequences are conserved. Secondary structure predictions suggest an additional
      resemblance to low-M(r) toxins and agglutinins. Northern (RNA) blot analysis and
      nuclear run-on assays demonstrated transcriptional control of expression of ssgA
      during nutrient deprivation and during formation of infection structures.
      Hybridizations of M. anisopliae genomic DNA indicate that there is only one form
      of ssgA in the genome.

PMID- 1398116
TI  - Characterization of the ilv-2 gene from Neurospora crassa encoding alpha-keto
      beta-hydroxylacyl reductoisomerase.
AB  - We have isolated the cDNA and corresponding genomic DNA for the ilv-2 locus of
      Neurospora crassa. This gene encodes alpha-keto-beta-hydroxylacyl
      reductoisomerase (Ilv-2), required for the synthesis of isoleucine and valine.
      The gene contains four introns, maps to the right arm of chromosome V, and
      encodes a protein of 400 amino acids (aa). Alignment of the aa sequence of Ilv-2
      with the two other known eukaryotic sequences encoding this enzyme reveals two
      conserved regions.

PMID- 1398118
TI  - Sequence of the complete osp operon encoding two major outer membrane proteins of
      a European Borrelia burgdorferi isolate (B29)
AB  - The nucleotide sequence of the operon encoding the major outer surface proteins,
      OspA and OspB, of a European isolate of Borrelia burgdorferi (strain B29) was
      determined and compared to the osp operon of the American strain, B31. An amino
      acid (aa) identity of 80.7% was found when comparing the OspA of B29 with that of
      B31, whereas the aa sequence of the OspB of B29 reveals only 61.3% identity with
      the OspB of B31. Thus, strains B31 and B29 can be regarded as representatives of
      different B. burgdorferi groups.

PMID- 1398119
TI  - Complete sequence of the major outer membrane protein-encoding gene of Chlamydia
      trachomatis serovar Da.
AB  - The complete nucleotide sequence of the gene omp1 encoding the major outer
      membrane protein (MOMP) of Chlamydia trachomatis serovar Da was determined
      following amplification by the polymerase chain reaction. The most closely
      related complete sequence published to date is that encoding the C. trachomatis
      L1 MOMP. When the L1 and Da MOMP deduced amino acid (aa) sequences were compared,
      16 single-aa differences located mostly in the variable domains I, II, and IV
      were detected. These regions contain the B-cell epitopes. Additional differences
      were found in the constant domains I and II, thought to participate in the T-cell
      response.

PMID- 1398120
TI  - Protein V, a novel type-II IgG receptor from Streptococcus sp.: sequence,
      homologies and putative Fc-binding site.
AB  - We have cloned and sequenced the Fc-receptor-encoding gene, fcrV, from a group G
      streptococcus. Considerable similarity was revealed between the FcRV, FcRA76 and
      M proteins of group A streptococci in their signal sequences and 3' termini, and
      between the Fc-binding regions of FcRV and FcRA76. The promoter and terminator
      regions showed no homology with those of the fcrA76 and M protein-encoding genes.
      The A1-A4 domains of FcrV (protein V) exhibit a heptapeptide repeat motif which
      is characteristic of alpha-helical coiled-coil proteins. The sequence, Ser-Asn
      Arg-Ala-Ala, in the outer position, 'f' of each domain is highly conserved and
      may be involved in FcR-IgG interactions.

PMID- 1398121
TI  - The sequence of the gene encoding elongation factor Tu from Chlamydia trachomatis
      compared with those of other organisms.
AB  - Nucleotide (nt) sequences encoding the elongation factor Tu (EF-Tu), tRNA(Thr)
      and tRNA(Trp) from Chlamydia trachomatis have been determined. The environment of
      the EF-Tu-encoding gene (tuf), between two tRNA gene sequences, suggests that it
      is part of a tufB locus. The nt sequence and the deduced amino acid (aa) sequence
      were aligned with comparable sequences from other organisms and the resulting
      data bases were used to infer phylogenies. Phylogenetic trees based on aa
      sequences and nt sequences are similar, but not completely congruent with rRNA
      gene-based phylogenies. Both the nt and aa sequence trees concur on the early
      divergence of Thermotoga and Chlamydia from the bacterial root. The aa alignment
      highlights the presence of four unique Cys residues in the chlamydial sequence
      which are found at strictly conserved positions in other sequences. Further
      peculiarities of the chlamydial and eubacterial sequences have been mapped to the
      X-ray crystallographic structure of the protein.

PMID- 1398122
TI  - The cell division cycle gene CDC60 encodes cytosolic leucyl-tRNA synthetase in
      Saccharomyces cerevisiae.
AB  - The cdc60 mutation (for cell division cycle) of the yeast, Saccharomyces
      cerevisiae, confers arrest at the START point of the cell cycle upon shift to the
      restrictive temperature [Bedard et al., Curr. Genet. 4 (1981) 205-214]. We have
      cloned the CDC60 gene by complementation of the temperature-sensitive phenotype.
      Sequence analysis revealed a single open reading frame of 3270 bp and the deduced
      amino acid sequence showed 50.5% sequence identity to the cytosolic leucyl-tRNA
      synthetase (LeuRS) from Neurospora crassa, implying that CDC60 encodes the
      corresponding yeast protein. Thus, CDC60 does not appear to be involved directly
      in the regulation of the cell cycle. Rather, the cdc60 mutation leads to cell
      cycle arrest at the nutrient control point START due to a deficiency of charged
      leucyl-tRNA. The CDC60 gene product also shows homology to LeuRSs from other
      organisms and to aminoacyl-RS for isoleucine, valine and methionine.

PMID- 1398123
TI  - Characterization of the XRN1 gene encoding a 5'-->3' exoribonuclease: sequence
      data and analysis of disparate protein and mRNA levels of gene-disrupted yeast
      cells.
AB  - Sequencing of the XRN1 gene of Saccharomyces cerevisiae, cloned in this
      laboratory as a gene encoding a 160-kDa 5'-->3' exoribonuclease (XRN1), shows
      that it is identical to a gene (DST2 or SEP1) encoding a DNA strand transferase
      and to genes involved in nuclear fusion, KEM1, and plasmid stability, RAR5. To
      better understand the various phenotypes associated with loss of XRN1 and the
      enzymatic activities associated with the protein, certain characteristics of our
      yeast cells lacking an active gene (xrn1) have been examined. Cells are larger
      (average volume is x 1.5-1.8) and have an increased doubling time (x1.9-2.1). The
      protein synthesis rate per cell is 80-90% that of wild-type (wt) cells, and the
      resultant cellular protein levels are higher. The rate of the 25S and 18S rRNA
      synthesis is approximately 45% that of wt cells and its cellular level is about
      90% that of wt cells. Levels of protein bands resolved by one-dimensional PAGE
      show substantial differences. Synthesis rates observed for the same protein
      bands, as well as measurements of several specific mRNA levels by Northern
      analysis, suggest disparities in mRNA levels. Results show two to four times
      longer half-lives of specific short-lived mRNAs. The variations in levels of
      protein and RNA species found in the xrn1 cells may be the cause of some of the
      phenotypes found associated with gene loss.

PMID- 1398124
TI  - Differential expression of the invertase-encoding SUC genes in Saccharomyces
      cerevisiae.
AB  - Invertase (INV) is encoded in Saccharomyces cerevisiae by a family of genes,
      comprising SUC1-SUC5 and SUC7. Production of INV is highly variable, dependent on
      the strain and SUC gene present in the cell. The differences in INV production
      derive from the structure of the genes or are dependent on the genetic background
      of the strain. Centromeric plasmids (based on YCp50) carrying one of the SUC
      genes (except SUC7) were introduced into a strain (SEY2101) lacking SUC genes.
      The INV produced by the transformants was dependent on the individual SUC genes,
      and correlated with INV mRNA levels. Plasmids in which SUC2 had been placed under
      control of promoters from the other SUC genes, were used to transform SEY2101
      cells. The amounts of INV produced by cells carrying hybrid SUC genes were in
      agreement with the levels expected if the promoter controlled the expression of
      the SUC2 structural region. It is suggested that the differences in expression
      are a function of the transcription efficiency of the different SUC gene
      promoters, based on the divergence of 5' sequences.

PMID- 1398125
TI  - An upstream activating sequence from the Aspergillus nidulans gpdA gene.
AB  - Introduction of a previously identified promoter element of the Aspergillus
      nidulans gpdA gene (encoding glyceraldehyde-3-phosphate dehydrogenase), the so
      called gpd box, into the upstream region of the highly regulated A. nidulans amdS
      gene (encoding acetamidase), significantly increased (up to 30-fold) the
      expression of the lacZ reporter gene fused to these expression signals. This
      increase was dependent on the orientation of the gpd box and on the site of
      introduction into the amdS upstream region. The presence of additional gpdA
      sequences which flank the gpd box reduced or even extinguished positive effects
      of the gpd box. omega-Amino acid and carbon catabolite regulation of the amdS
      promoter were retained after introduction of the gpd box, indicating that the gpd
      box does not abolish interactions of the regulatory proteins, AmdR and CreA, with
      the amdS transcription control sequences. Based on the results, it is suggested
      that the gpd box comprises at least two separate activities: one being
      orientation dependent, but relatively independent of position of the gpd box in
      the upstream region, and the other is only functional near other sites of
      transcriptional control. Most likely, both activities are not involved in
      regulation of the amdS promoter.

PMID- 1398126
TI  - The nitrate reductase-encoding gene of Volvox carteri: map location, sequence and
      induction kinetics.
AB  - The nitrate reductase (NR) structural gene (nitA) of Volvox carteri has been
      cloned and characterized. There is a single copy of this gene in the genome, and
      RFLP (restriction-fragment length polymorphism) analysis assigns it to the
      previously defined nitA/chlR locus on linkage group IX, 20-30 cM from the two
      beta-tubulin-encoding loci. Determination of the 5871-nt sequence of the coding
      region of genomic clones, and comparisons to a cDNA sequence, revealed ten
      introns and eleven exons that encode a 864-aa polypeptide. Detailed comparisons
      with higher-plant and fungal NRs indicate that, whereas the aa sequence is
      strongly conserved within functional domains for the flavin adenine dinucleotide
      , heme- and molybdenum-pterin cofactor-binding sites, substantial differences in
      the aa sequence occur in the N-terminal end and the two inter-domain regions. Two
      potential transcription start points 439 and 452 nt upstream from the start codon
      and a polyadenylation signal 355 nt downstream from the stop codon have been
      identified by primer-extension analysis and cDNA sequencing, respectively.
      Accumulation of the nitA transcript is both induced by nitrate and repressed by
      ammonium and urea: after the organism is transferred from ammonium to nitrate as
      the nitrogen source, a 3.6-kb NR transcript is readily detectable on Northern
      blots by 10 min, reaches maximum abundance by 30 min, and then rapidly declines
      to an intermediate level that is subsequently maintained. Substantial induction
      by nitrate is observed at the end of the dark portion of the daily light/dark
      cycle, but the inductive response peaks in the first hour of the light
      period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398127
TI  - Construction of lambda gt103, a derivative of phage lambda gt10 that has unique
      EcoRI, NotI, SacI and SpeI sites and retains positive selection for recombinants.
AB  - A phage vector, lambda gt103, that has unique EcoRI, NotI, SacI and SpeI sites
      within the imm434 cI repressor gene, was constructed by PCR-aided site-directed
      mutagenesis of lambda gt10 [Huynh et al., DNA Cloning Techniques: A Practical
      Approach, 1985, pp. 49-78]. This vector allows directional cloning and retains
      positive selection for recombinants on Escherichia coli C600hfl strains (since
      only phages with disrupted cI genes plate on this host). Libraries made with this
      phage vector can be efficiently screened for clones in which a part of the insert
      is homologous to probe DNAs derived from a plasmid-based library, without cross
      hybridization.

PMID- 1398128
TI  - Derivation of a mathematical expression useful for the construction of complete
      genomic libraries.
AB  - We present and derive a formula that is useful for the design and evaluation of
      gene cloning experiments in which a complete gene library of the entire genome of
      an organism is desired. The formula n = ln(1-phi f)/ln(1-f) (in which n is the
      number of recombinant clones required to ensure a probability, phi, of obtaining
      at least one of each of all possible gene sequences, and f is the fraction of the
      genome contained in an average-sized DNA fragment) applies to construction of
      libraries, in which at least one copy of all the genetic information of a genome
      is required. The use of this formula for quantitative evaluation of genomic
      libraries should give greater assurance that a given library would be complete.

PMID- 1398129
TI  - Comparison of the complete sequence of the str operon in Salmonella typhimurium
      and Escherichia coli.
AB  - The nucleotide (nt) sequences of the str operon in Escherichia coli K-12 and
      Salmonella typhimurium LT2 were completed and compared at the nt and amino acid
      (aa) level. The order of conservation at the nt and aa level is rpsL greater than
      tufA greater than rpsG greater than f usA. A striking difference is that the rpsG
      encoded ribosomal protein, S7, in E. coli K-12 is 23 aa longer than in S.
      typhimurium. The very low (0.18) codon adaptation index of this part of the E.
      coli K-12-encoding gene and the unusual stop codon (UGA) suggest that this is a
      relatively recent extension. A trend towards a higher G+C content in fusA (gene
      encoding elongation factor (EF)-G) and tufA (gene encoding EF-Tu) in S.
      typhimurium is noted. In fusA, nt substitutions at all three positions in a codon
      occur at a much higher frequency than expected from the number of nt
      substitutions in the gene, assuming they are random and independent events. An
      analysis of substitutions in this and other genes suggests that the triple
      substitutions in fusA, and some other genes, are the result of the sequential
      accumulation of individual mutations, probably driven by selection pressure for
      particular codons or aa.

PMID- 1398130
TI  - Acanthamoeba castellanii RNA polymerase II transcription in vitro: accurate
      initiation at the adenovirus major late promoter.
AB  - We have developed and characterized an efficient in vitro system from the
      protozoan, Acanthamoeba castellanii, that accurately initiates transcription from
      the adenovirus-2 major late promoter (AdMLP). Transcription by A. castellanii RNA
      polymerase II (pol II) is initiated at the same nucleotide (nt) that is used by
      HeLa extracts and is dependent upon adenovirus sequences located between nt -51
      and the region around the transcription start point (tsp). The results suggest
      that the A. castellanii transcription factors for pol II which determine the tsp
      and the promoter elements that they recognize have been functionally conserved
      during evolution.

PMID- 1398131
TI  - The flax ribosomal RNA-encoding genes are arranged in tandem at a single locus
      interspersed by 'non-rDNA' sequences.
AB  - The ribosomal RNA (rRNA)-encoding genes (rDNA) in flax, estimated to be present
      in about 2400 copies per diploid nucleus, have been reported as a single
      homogeneous repeat unit of 8.6 kb. In situ hybridization analysis indicated that
      these genes were located at a single site on one pair of chromosomes. However, an
      analysis of a flax variety, CI 1303, has revealed heterogeneity in the intergenic
      spacer of the rDNA repeat unit. A genetic analysis of rDNA inheritance in two
      flax lines, Stormont Cirrus and CI 1303, has again supported the observation that
      there is a single rDNA locus in this plant species. Screening of four different
      genomic libraries made in methylation-sensitive and -insensitive systems, and the
      analysis of 40 phage clones, demonstrate a much higher number than that expected
      of junctions between rDNA and non-rDNA. Direct evidence of rRNA-encoding genes
      being present in tandem comes from a few phage clones that contain more than two
      rDNA repeats. The evidence presented here indicates that rDNA, although present
      at a single locus in tandem arrays, may be interrupted frequently by other non
      rDNA sequences, thus giving rise to questions about their organization into long
      tandem arrays.

PMID- 1398132
TI  - Evolution and differential expression of the (1-->3)-beta-glucan endohydrolase
      encoding gene family in barley, Hordeum vulgare.
AB  - The (1-->3)-beta-D-glucan glucanohydrolases [(1-->3)-GGH; EC 3.2.1.39] of barley
      (Hordeum vulgare L., cv Clipper) are encoded by a small gene family. Amino acid
      sequences deduced from cDNA and genomic clones for six members of the family
      exhibit overall positional identities ranging from 44% to 78%. Specific DNA and
      oligodeoxyribonucleotide (oligo) probes have been used to demonstrate that the (1
      ->3)-GGH-encoding genes are differentially transcribed in young roots, young
      leaves and the aleurone of germinated grain. The high degree of sequence
      homology, coupled with characteristic patterns of codon usage and insertion of a
      single intron at a highly conserved position in the signal peptide region,
      indicate that the genes have shared a common evolutionary history. Similar
      structural features in genes encoding barley (1-->3,1-->4)-beta-glucan 4
      glucanohydrolases [(1-->3,1-->4)-GGH; EC 3.2.1.73] further indicate that the (1-
      >3)-GGHs and (1-->3,1-->4)-GGHs are derived from a single 'super' gene family, in
      which genes encoding enzymes with related yet quite distinct substrate
      specificities have evolved, with an associated specialization of function. The (1
      ->3,1-->4)-GGHs mediate in plant cell wall metabolism through their ability to
      hydrolyse the (1-->3,1-->4)-beta-glucans that are the major constituents in
      barley walls, while the (1-->3)-GGHs, which are unable to degrade the plant (1-
      >3,1-->4)-beta-glucans, can hydrolyse the (1-->3)- and (1-->3,1-->6)-beta-glucans
      of fungal cell walls.

PMID- 1398133
TI  - Construction of a chimeric viral gene expressing plum pox virus coat protein.
AB  - The capsid-encoding gene of plum pox virus (PPV) was fused with the leader
      sequence of the coat protein mRNA (cp) of tobacco mosaic virus by a novel
      mutagenesis technique which involves reverse transcription of minus-strand RNA
      [synthesized by in vitro transcription of a double-stranded (ds) cDNA clone],
      using an ad hoc synthetic oligodeoxynucleotide as primer. The resulting cDNA was
      rendered ds and cloned into the plasmid, pBluescribe M13+. Transcription of this
      chimeric construction produced RNA molecules of 1250 nucleotides in length, which
      were used as messengers in the in vitro protein-synthesizing systems. The major
      product of this transcript consists of a 36-kDa polypeptide and was identified as
      the PPV coat protein (CP) by molecular weight estimation and by
      immunoprecipitation with a polyclonal antiserum to PPV. Transfer of this cDNA via
      Agrobacterium tumefaciens into plants was successfully performed. Transgenic
      Nicotiana plants producing the PPV CP were subsequently obtained.

PMID- 1398134
TI  - Comparison of the sequence and structure of transcription factor IIIA from Bufo
      americanus and Rana pipiens.
AB  - Amino acid (aa) sequences of transcription factor IIIA (TFIIIA) from the toad,
      Bufo americanus, and the grass frog, Rana pipiens, were determined by cDNA
      cloning and DNA sequencing. The 3'-untranslated regions of the cDNAs reveal that
      the TFIIIA gene polyadenylation signal is ATTAAA, rather than the conventional
      AATAAA. The B. americanus and R. pipiens proteins share about 60% aa sequence
      homology with each other and with Xenopus laevis TFIIIA. Although these results
      indicate that TFIIIA has more sequence variation than other DNA-binding proteins,
      a number of conserved features are evident and of likely functional significance.
      These include potential guanine nucleotide-binding sites at arginines in zinc
      fingers (ZnF) II, V, and IX, acidic residues between metal-coordinating
      cysteines, and a basic region in the C-terminal tail possibly involved in
      transcription promotion. Sequence similarity also exists in an aa stretch
      bridging the ninth ZnF and C-terminal tail of both TFIIIA and the 5S RNA-binding
      protein, p43. DNase I protection analyses demonstrate that B. americanus and R.
      pipiens TFIIIA interact with the internal control region (ICR) of the Xenopus
      borealis 5S RNA-encoding gene (5S) in different manners: the B. americanus
      interaction is similar to X. laevis TFIIIA, protecting the entire 5S gene ICR (nt
      +96 to +43) from DNase I digestion, whereas the R. pipiens TFIIIA strongly
      protects the ICR from nt +96 up to +78 and less strongly from +78 to +43.
      Possibly accounting for the binding differences observed, R. pipiens and R.
      catesbeiana oocyte 5S RNAs (and by inference 5S genes) were found to contain a G
      or U at nt position 50 while B. americanus, X. laevis, and other eukaryotic 5S
      RNAs have an A in the analogous position (nt 53 in generalized eukaryotic
      structure).

PMID- 1398135
TI  - Determination of the sequence of an expressible cDNA clone encoding
      ERp60/calregulin by the use of a novel nested set method.
AB  - An analysis of the N-terminal sequence of the luminal endoplasmic reticulum
      protein, ERp60, showed that it was identical to the well-characterized Ca2+
      binding protein, calregulin. A full-length, expressible cDNA clone encoding this
      protein was isolated from a mouse fibroblast cDNA library. A novel nested set
      strategy for the production of overlapping fragments for DNA sequencing was used
      to determine the complete nucleotide (nt) sequence of both strands of the ERp60
      clone. This method utilizes a series of nonspecific deletion primers in
      conjunction with a specific site primer to generate the nested set fragments.
      This procedure possesses several advantages over other nested set techniques,
      since it does not require (i) the re-cloning of the DNA insert into other
      vectors, (ii) any prior knowledge of the restriction sites of the nt sequence, or
      (iii) the transformation and analysis of bacterial subclones. ERp60 has a 17
      amino acid (aa) signal sequence and the mature protein contains 399 aa with a
      calculated M(r) of 46,347.

PMID- 1398136
TI  - Two mRNAs exist for the Hs PROS-30 gene encoding a component of human prosomes.
AB  - Screening of a lambda gt11 cDNA expression library of the HeLa cell genome with a
      monoclonal antibody that specifically recognizes prosomal 30-33-kDa proteins,
      allowed isolation of a 1264-nucleotide (nt) recombinant cDNA containing a 327-nt
      untranslated 5'-end. The amino acid (aa) sequence deduced from this cDNA revealed
      a protein of 269 aa (M(r) of 30,227) that includes a consensus box characteristic
      for Tyr phosphorylation, also observed in other prosomal proteins. Comparison
      with another prosomal 27-kDa protein, cloned in our laboratory, indicated the
      presence of three prosome-specific homology boxes observed in these proteins from
      archaebacteria to man. Interestingly, except for the untranslated 5'-end, as well
      as the sequence coding for the N-terminal six aa, this cDNA is identical to two
      recently published cDNAs encoding subunit C2 of human liver proteasome [Tamura et
      al., Biochim. Biophys. Acta 1089 (1991) 95-102] and subunit NU of human
      erythrocyte macropain [DeMartino et al., Biochim. Biophys. Acta 1079 (1991) 29
      38]. Primer extension and Northern blot analysis using two specific 18-mer
      oligodeoxyribonucleotides indicated the presence of two mRNAs that have divergent
      5'-ends. These results, as confirmed by the polymerase chain reaction, establish
      the existence of two distinct Hs PROS-30 mRNAs, differing in their 5'-noncoding
      regions and in the N-terminal six aa of their protein products.

PMID- 1398137
TI  - Primary structure of a chitinase-encoding gene (chi1) from the filamentous fungus
      Aphanocladium album: similarity to bacterial chitinases.
AB  - Chitinase 1 (Chi1) is the major extracellular chitinase from the hyperparasitic
      fungus, Aphanocladium album. We determined the complete sequence of the
      chromosomal and cDNA copies of the structural gene (chi1) coding for Chi1. The
      coding region is interrupted by three short introns (55, 53 and 49 bp long). Chi1
      is 423 aa long and begins with a stretch of 34 aa not found in the mature
      protein. The Chi1 sequence presents overall similarities with bacterial
      chitinases from Serratia marcescens and Bacillus circulans. Compared with other
      chitinases, A. album Chi1 has only two short similarity regions (12 and 8 aa
      long), which are also found in bacterial, yeast and some plant chitinases.

PMID- 1398138
TI  - Sequence comparison of the Caenorhabditis elegans dpy-13 and col-34 genes, and
      their deduced collagen products.
AB  - A 2232-nucleotide sequence spanning the col-34 gene from the nematode,
      Caenorhabditis elegans, is presented. This gene, which encodes a collagen protein
      (Clg), is transcribed from right to left with respect to the genetic map, and
      convergently with the nearby dpy-13 gene which also encodes a Clg. Both col-34
      and dpy-13 have 5'-flanking elements in common with each other and also with
      other nematode Clg-encoding genes (clg). One element, variants of which are
      shared by col-7, col-19 and dpy-13, is predicted to be a target for a number of
      regulatory molecules, possibly including the ceh-18 product, a nematode POU
      domain protein. The deduced amino acid sequence of Col-34 has a high degree of
      homology with the Dpy-13 collagen, although there are significant differences. In
      particular, one region of Dpy-13, which is predicted to have secondary structure
      different from Col-34, is altered by the recessive dpy-13(e225) mutation.

PMID- 1398139
TI  - Cloning and characterization of KM190, a specific satellite DNA family of
      Drosophila kitumensis and D. microlabis.
AB  - The nucleotide sequences of nine clones, pKA191/1-4 from Drosophila kitumensis
      and pMR190/1-5 from D. microlabis, were determined. They represent a tandemly
      arranged and highly repetitive satellite DNA family, KM190, which is specific for
      the two species.

PMID- 1398140
TI  - The Xenopus U7 snRNA-encoding gene has an unusually compact structure.
AB  - A subclone containing a single Xenopus borealis U7 snRNA-encoding gene has been
      microinjected into X. laevis oocyte nuclei to examine its expression using
      [32P]GTP as an in vivo label. Only two U7 snRNA bands were detected after
      incubation, and subsequent fractionation of the oocyte showed that only the
      larger transcript is present in the nucleus. The sequence of this functional U7
      gene shows that, in addition to the coding region, it contains, in the
      appropriate locations, the 3'-box and proximal sequence element (PSE) which are
      typical of Pol II-transcribed snRNA genes. Surprisingly, the Xenopus U7 gene
      contains two adjacent octamer-binding motifs located only 12 and 24 bp upstream
      from the PSE, instead of the usual location around 150-200 bp upstream. No other
      cis-acting elements appear to be present. A 5' deletion analysis shows that the
      transcription level of this U7 gene remains constant if sequences upstream of the
      two octamer motifs are removed, yet is undetectable when an additional 34 bp
      containing both octamers and the PSE are removed. This confirms that the Xenopus
      U7 gene is the most compact snRNA-encoding gene isolated to date. A comparison of
      U7 sequences shows there is a much greater conservation in the 5' half of the
      molecule, which contains sequences that base-pair with target pre-mRNA, than in
      the 3' half which can form a single stem-loop structure that varies in size.

PMID- 1398141
TI  - Structure of the rainbow trout metallothionein A gene.
AB  - To investigate the regulation of metallothionein-encoding genes in fish, we have
      isolated and sequenced the rainbow trout metallothionein-A-encoding gene (tMT-A)
      by polymerase chain reaction. This gene spans about 1.1 kb, consists of three
      exons and two introns, and has an A+T-rich 5'-region which contains a TATAAA
      signal, and two metal responsive elements (MREs). The transcription start point
      is centered around an A residue 81 nt upstream of the ATG codon.

PMID- 1398142
TI  - A high-level expression vector for human cells.
AB  - We have developed a vector (pSupexp), for high-level expression of genes, that is
      dependent on transactivation of the human immunodeficiency virus 1 (HIV-1) long
      terminal repeat (LTR) by the HIV-1 transactivator protein, Tat. The foreign gene,
      expressed under transcriptional control of the HIV-1 LTR, and the tat gene,
      expressed under transcriptional control of SV40 early promoter, are expressed
      from the same plasmid. The vector also has the neomycin resistance-encoding gene
      (neo), with G418 being used as a dominant selection marker for stable expression.
      We have cloned the bacterial cat gene into pSupexp and measured transient CAT
      production in human HeLa and A549 cells. Our results indicate that pSupexpCAT
      expresses about 25- to 68-fold higher levels of CAT activity as compared to other
      standard SV40- and Rous sarcoma virus-based vectors, and three- to fivefold more
      activity than the cytomegalovirus-based vector. Immunoprecipitation of the CAT
      protein also revealed a high level of production in human cells.

PMID- 1398143
TI  - Cloning, expression and tissue distribution of the gene encoding rat fibroblast
      growth factor receptor subtype 4.
AB  - The rat homologue of the gene encoding the fibroblast growth factor receptor
      subtype 4 (FGFR4) was cloned from rat lung mRNA, and the cDNA sequence was found
      to be 95% similar and 92% identical to the human homologue. Northern blot
      analysis of adult rat tissues demonstrated that a 3.1-kb mRNA encoding FGFR4 is
      detectable only in the lung and kidney. The receptor variant described here
      encodes two potential immunoglobulin-like domains, 21 hydrophobic amino acids
      encoding a potential transmembrane domain, and a split tyrosine kinase motif.
      However, the acidic box and hydrophobic signal peptide domains are not present in
      this cDNA isolate.

PMID- 1398144
TI  - Regulatory elements for the tissue-specific expression of the rat serine
      dehydratase-encoding gene.
AB  - L-Serine dehydratase (SDH; EC 4.2.1.13), the key enzyme for serine utilization in
      the rat, is synthesized primarily in the liver. Cis-acting DNA elements required
      for liver-specific expression of the SDH gene were identified by two approaches:
      (1) transient expression assays in primary cultured rat hepatocytes, and in rat
      fibrosarcoma and normal rat kidney epithelial (NRK-52E) cell lines; and (2) in
      vitro transcription assays with nuclear extracts prepared from rat liver and
      spleen. Deletion analyses of the 5' flanking sequences of the gene have defined
      two functionally different regions: (a) a cell-type-specific promoter located
      between positions -62 and +10, which is sufficient for liver-specific expression;
      and (b) a distal promoter region between bp -133 and -63 containing positive cis
      acting elements that regulate the promoter activity in a non-tissue-specific
      fashion. No other cis-acting elements essential for liver-specific expression
      were found in the region of -134 to 2.1 kb upstream relative to the cap site of
      SDH.

PMID- 1398145
TI  - Sequences for two cDNAs encoding Arabidopsis thaliana eukaryotic protein
      synthesis initiation factor 4A.
AB  - Two distinct cDNAs encoding protein synthesis initiation factor 4A (eIF-4A) were
      isolated from an Arabidopsis thaliana cDNA library and sequenced. The deduced
      amino acid sequences from the two cDNAs were compared to eIF-4A from tobacco,
      mouse and Saccharomyces cerevisiae. The putative ATP-binding sites and RNA
      helicase motifs were identified.

PMID- 1398146
TI  - Sequence of a cDNA encoding the alpha-subunit of wheat translation elongation
      factor 1.
AB  - A cDNA encoding the alpha-subunit of wheat protein synthesis elongation factor 1
      (EF-1 alpha) was isolated from a wheat cDNA expression library and sequenced. The
      deduced amino acid sequence is compared to EF-1 alpha from other species and to
      elongation factor Tu (EF-Tu) from Escherichia coli. Putative GTP-binding sites
      are identified.

PMID- 1398147
TI  - Sequence analysis of a second cDNA encoding Atlantic salmon (Salmo salar) serum
      albumin.
AB  - Two similar, but distinct, cDNAs for Atlantic salmon serum albumin have been
      isolated from the same salmon liver. Comparison between the asSA-1 and asSA-2
      sequences reveals 1% overall sequence difference.

PMID- 1398148
TI  - Cloning and sequencing of a cDNA encoding mouse stromelysin 1.
AB  - A cDNA encoding mouse stromelysin 1 was cloned and the 1740-bp sequence was
      determined. The deduced amino acid (aa) sequence was compared with stromelysin 1
      sequences of other mammals. Comparison with a previously published incomplete aa
      sequence of mouse stromelysin 1 revealed three single aa differences.

PMID- 1398149
TI  - A rabbit AldA pseudogene derived from a partially spliced primary aldolase A
      transcript.
AB  - The entire AldA processed pseudogene of rabbit was isolated and characterized.
      The pseudogene encodes the C-terminal portion of the protein from amino acids
      (aa) 126-363. There are deletions, insertions and nucleotide (nt) substitutions
      distributed throughout the 931 bp of identity shared with the 1.4-kb mRNA. There
      are 21 replacement codon substitutions, including a clearly deleterious change in
      the stop codon. This processed pseudogene has several uncommon features: (i) it
      has a 5'-boundary coincident with an intron/exon junction and does not encode the
      entire mRNA, (ii) there is a broken direct repeat that overlaps the region of
      shared identity with the mRNA rather than flanking it, and (iii) there is no
      poly(A) sequence. This processed pseudogene probably arose by integration of a
      DNA copy of a partially spliced primary transcript. The structure of this gene
      has added implications for the timing of posttranscriptional processing events.

PMID- 1398151
TI  - First South-North Human Genome Conference--Caxambu, Brazil, 12-15 May 1992.

PMID- 1398150
TI  - Sequence of a canine cDNA clone encoding a Ran/TC4 GTP-binding protein.
AB  - We report the isolation and characterization of a canine cDNA encoding a 216
      amino acid GTP-binding protein of the Ras superfamily. The protein is almost
      identical to the human TC4 [Drivas et al., Mol. Cell. Biol. 10 (1990) 1793-1798]
      and Ran [Bischoff and Ponstingl, Proc. Natl. Acad. Sci. USA 88 (1991) 10830
      10834; Nature 354 (1991) 80-82] proteins, the latter of which has been found to
      be involved in cell cycle control. Furthermore, the protein is highly similar to
      the fission yeast spi1 gene product [Matsumoto and Beach, Cell 66 (1991) 347
      360]. The high degree of evolutionary conservation in this protein suggests that
      it plays a vital role in the eukaryotic cell.

PMID- 1398152
TI  - [Theodor Kocher: surgery and ethics].
AB  - Theodor Kocher's (1841-1917) creative participation in the rise of modern surgery
      and his internationally prominent standing therein at the turn of the century are
      briefly outlined. Kocher experienced, however, the last decade of his career as a
      period of transition. First new developments within medicine and surgery
      questioned some of the new "radical" operations by then seen as sole progressive
      therapeutic possibilities. Second, new emotional and ethical conflicts ensued for
      the solution of which the traditional ethos (viz. "to help and to do no harm")
      was felt to be insufficient: The choice between two therapeutic possibilities and
      the unjustice of socially stratified treatment. Kocher tried to cope with this
      transition scientifically by promoting basic research, emotionally and ethically
      by explicitly stressing his long familiar Christian faith.

PMID- 1398153
TI  - The emergence of endocrinology.
AB  - Endocrinology was recognized as a new branch of biological science mainly as a
      result of events which took place between about 1890 and 1905, but ideas and
      discoveries dating from antiquity contributed to it also. Experiments supporting
      the concept of internal secretions by the testicles were described by Aristotle
      (4th c. B.C.) and by Hunter (18th c.) and Berthold (19th c.). In 1855 Bernard
      described glucose as an internal secretion of the liver and Addison reported the
      effects of adrenal disease in man. Adrenalectomy was fatal in animals. Goitre was
      known in antiquity and cretinism had been described by Paracelsus. Myxoedema was
      reported by Gull in 1873, and Kocher described cachexia strumipriva in 1883. In
      1888 cretinism, myxoedema and cachexia strumipriva were attributed to thyroid
      insufficiency. In the 1890s Gley found that tetany after thyroidectomy was due to
      removal of the parathyroids. In 1884 Rehn proposed that toxic goitre was due to
      thyroid excess. In 1889 Brown-Sequard claimed that injections of testicular
      extract rejuvenated the elderly, and in 1893 he introduced organotherapy. In 1891
      Murray treated myxoedema successfully with thyroid extract. In 1893 Oliver and
      Schafer found that an adrenal extract raised the blood pressure, and soon
      adrenaline was extracted from the adrenal medulla. Adrenocortical deficiency was
      proposed as the cause of Addison's disease, and in 1896 Osler prepared an extract
      which relieved one patient. Diabetes mellitus, described in the first century,
      was usually fatal. Thirst and polyuria followed experimental pancreatectomy, and
      pancreatic lesions were found in some human diabetics. In the 19th century
      workers in France and Germany found that diabetes resulted from absence of an
      internal secretion by the islets of Langerhans and, in 1893, Laguesse described
      the function of the islets as "endocrine". In 1895 Beatson treated advanced
      breast cancer successfully by oophorectomy. In 1895 Schafer commended study of
      the internal secretions to physiologists. In 1902 Bayliss and Starling discovered
      secretin, a chemical messenger secreted by the intestinal mucosa. In 1905
      Starling proposed the name "hormone" for this class of internal secretions. By
      then endocrinology had been launched as a new branch of science. The crucial
      events which led to the recognition of endocrinology as a new branch of
      biological science took place between about 1890 and 1905. Many ideas and
      discoveries dating from antiquity and apparently unrelated at first had, however,
      contributed to it. Most of the organs and tissues that form the endocrine system
      were recognized over 100 years ago.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1398155
TI  - [Theodor Kocher and the beginnings of radiology in Switzerland].
AB  - Already in January 1896, Kocher ordered his first clinical radiography. It was
      executed by Aime Forster, professor of physics at the University ob Berne.
      Together, Forster and Kocher elaborated the plans for the Rontgen Institute of
      the Inselspital, which opened on January 1st, 1898.

PMID- 1398154
TI  - [The research of Theodor Kocher on the etiology of osteomyelitis and acute
      struma].
AB  - In 1879, Kocher demonstrated experimentally that osteomyelitis is an infectious
      disease which is caused by a non-specific microorganism (the "micrococcus"). He
      showed that the infection of the bone marrow is the consequence of a hematogenous
      dissemination of a local infection, either cutaneous or mucous. The clinical and
      pathological form of the disease depends not only on the virulence of the
      microorganism, but also on the state of the tissue in which it develops. In the
      same year, Kocher suggested that acute strumitis (inflammation of the goitre) has
      the same aetiology; he did not, however, produce any experimental evidence for
      this. Thus, Kocher defined in an original way infection as the result of an
      interaction between a microorganism and his host.

PMID- 1398156
TI  - [Theodor Kocher and Zurich].
AB  - Theodor Kocher was linked to Zurich by many relationships. It was in this town
      that he spent his last semester at university, and his contacts with his teachers
      Friedrich Horner and Theodor Billroth were of some importance with regard to his
      election as a professor at Berne. Kocher was on friendly terms with his Zurich
      colleagues Rudolf Ulrich Kronlein and Ferdinand Sauerbruch. In spite of many
      common views, however, the two Swiss surgeons Kocher and Kronlein were not always
      of the same opinion.

PMID- 1398157
TI  - [Theodor Kocher and Cesar Roux].
AB  - 96 letters addressed by Cesar Roux (1857-1934), the most prestigious surgeon from
      the Canton of Vaud, to his fiancee, Anna Begoune, native of Russia, allow us to
      evoke Roux's training in Kocher's department of surgery. The letters shed light
      on Roux's relationship with Theodor Kocher, whom he compares successively with
      Billroth and von Volkmann.

PMID- 1398158
TI  - [The inclusion of Theodor Kocher in the work of the Trieste surgeon Gustavo
      Usiglio on thyroid gland tumors (1894)].
AB  - Gustavo Usiglio (1855-1933), a pupil of Billroth, was a surgeon of high
      qualities. The present author analyzes his main scientific work "On the tumours
      of the thyroid and their cure"; the book, which deals essentially with goitre,
      was published in 1894 at Milan and, in a 2nd edition, in 1895 at Trieste.
      Especially in the final chapter on therapeutics, Usiglio reveals himself as a
      fervent follower of Kocher.

PMID- 1398159
TI  - Surgery for exophthalmic goitre in Australia, 1907.
AB  - Thomas Dunhill 1876-1957, Australian born surgeon (Melbourne 1907-1914 and London
      1920-1941) performed partial thyroidectomy for exophthalmic goitre using Th.
      Kocher's method of local anaesthesia on seven consecutive severely toxic patients
      in 1907 with a successful outcome in all seven. A brief outline of the life and
      achievements of Thomas Dunhill is appended.

PMID- 1398160
TI  - [Relations of Theodor Kocher with the "International Society of Surgery". His
      role as the 1st congress president].
AB  - With the aim of promoting progress in surgery through the friendly exchange of
      views and experience, the first International Society of Surgery was founded at
      Brussels in 1902, hereby helping to overcome the narrow boundaries of that times'
      nationalism. At its first congress, the "International Society of Surgery (ISS)",
      otherwise known by its French name "Societe Internationale de Chirurgie (SIC)",
      numbered already 638 members, amongst them the most important surgeons from all
      over the world. Theodor Kocher was the president of the first congress, held at
      Brussels in 1905, and was also responsible for the choice of topics. His
      presidential address clearly reflected the high aims the Society set itself.
      Kocher's personal and professional authority, his surgical skill, which he liked
      so much to communicate to his colleagues, and his internationally minded thinking
      shaped the young society. He remained in the international committee of the ISS
      until his death in 1917.

PMID- 1398161
TI  - [The Zurich lazarette in the wars of 1798/99. A manuscript by the hospital
      physician Johann Ludwig Meyer].
AB  - A manuscript, written about 1825, by the Zurich surgeon Johann Ludwig Meyer (1782
      1852), is kept at the Institute and Museum of Medical History of the University
      of Zurich. The author describes his surgical observations in the makeshift
      military hospitals in Zurich during the French occupation of 1798 and the 2nd
      Coalition War in 1799. Together with Johannes Grimm, the then 16-year-old Meyer
      worked as an assistant to his father Konrad Meyer, the senior surgeon of Zurich,
      giving surgical treatment to wounded officers and soldiers in the French,
      Austrian and Russian military hospitals.

PMID- 1398162
TI  - [Rural physician 300 years ago. The Lucerne surgeon and obstetrician Klaus
      Melchior Brundler (1721)].

PMID- 1398163
TI  - [Heavy metals in the mother-newborn infant biological system in the technology
      related biogeochemical environment].
AB  - High levels of the lead, cadmium and zinc content in the mother and newborn
      blood, placenta, meconium and breast milk in the zinc production metallurgical
      works area were shown. Intoxication of newborns may be caused by breast feeding
      with milk containing heavy metals.

PMID- 1398164
TI  - [Urinary excretion of chemical elements in technology-related environmental
      pollution].

PMID- 1398165
TI  - [Air pollution in the region of petroleum-processing plant].

PMID- 1398166
TI  - [Hygienic evaluation of the level and activity of mercury in reservoir water].

PMID- 1398167
TI  - [Hygienic evaluation of the effectiveness of removing pesticides during water
      purification].

PMID- 1398168
TI  - [Combined effects of styrol vapors and general vibration in a subacute
      experiment].

PMID- 1398169
TI  - [Hygienic characteristics of working conditions and morbidity at the present-day
      cotton seed-processing industry].

PMID- 1398170
TI  - [Hygienic evaluation of the physical activity programs for schoolchildren].
AB  - Theoretical prerequisites for a complex approach to making the hygienic standards
      of schoolchildren's motor regimes are discussed. Experimental evidence for the
      impact of the regimes on the development of schoolchildren is given.

PMID- 1398171
TI  - [Estimation of current maximum permissible levels of total specific activity of
      radionuclide mixture in the liquid forms of drugs and medicinal raw materials].
AB  - Algorithm of assessment of allowable levels of the total specific activity of
      radionuclides in liquid medicaments and medical raw materials was worked up. The
      key radionuclides were Strontium-90, Caesium-134 and -137.

PMID- 1398172
TI  - [Hygienic evaluation of the effect of high-frequency electromagnetic field on the
      immunologic reactivity of the body].

PMID- 1398173
TI  - [Evaluation of the neurobiological defense system of the body after exposure to
      complex environmental factors].
AB  - Effect of the air and water pollution complex on the rat neurobiological defense
      system (emotional reactivity, aggressiveness, forming and keeping of memory
      "traces", social and sexual options and so on) was investigated. Changes in
      behavioral reactions were noted. These changes correlated with the level of
      pollution.

PMID- 1398174
TI  - [Allergological examination of the population living in the territory of the Amur
      Yakut railroad].

PMID- 1398175
TI  - [Problems and prospects of morphological studies in hygiene].

PMID- 1398176
TI  - [Mechanism of the toxic effect of T-2 toxin].

PMID- 1398177
TI  - [Experimental study of benzotrichloride metabolism].

PMID- 1398178
TI  - [European Charter on the Protection of the Environment and Human Health].

PMID- 1398179
TI  - [History of the sanitary epidemiological services in the railroad
      transportation].

PMID- 1398180
TI  - [Introduction of the contract method to the activities of a sanitary
      epidemiological station].

PMID- 1398181
TI  - [Determining the levels of lead in urine and blood by a chrono- potentiometric
      method].

PMID- 1398182
TI  - [Principles of substantiation of biological safety in working with pathogenic
      microorganisms].

PMID- 1398183
TI  - [Use of thin layer chromatography for analysis of plasticizers of cellulose
      ethers].

PMID- 1398185
TI  - [Analysis of resins in the air, water and sugar beet leaves and roots by the
      method of thin layer chromatography].

PMID- 1398184
TI  - [Heavy metals in the environment and their effects on the body (review of the
      literature)].

PMID- 1398186
TI  - [Calculation of the median effective dose and median effective time using a
      generalized model based on the Waibull distribution].

PMID- 1398188
TI  - [Ionometric analysis of fluorides in the soil].

PMID- 1398187
TI  - [Changes in specific reaction of erythrocytes to the antigen after administration
      of methylene blue and sodium azide].

PMID- 1398190
TI  - [Rapid evaluation of embryotoxic properties of substances in the culture of
      preimplantation zygote].

PMID- 1398189
TI  - [A method of calculating the time of death of laboratory animals in an acute
      experiment].

PMID- 1398191
TI  - [Use of an automated complex of the "filter" type for evaluation of the status of
      the autonomic nervous system].

PMID- 1398192
TI  - [A method of rapid evaluation of the levels of chemical substances using
      biological testing].

PMID- 1398193
TI  - [Evaluation of the levels of heavy metals in hair].

PMID- 1398195
TI  - [Systems analysis of toxico-kinetic laws based on the chamber modeling in the
      light of the tasks of hygienic toxicology].

PMID- 1398194
TI  - [Concerning the article by A.D. Frolova, E.L. Dolgopolova and T.G. Martinson
      "Rapid prediction of the safe degree of action of poorly soluble dusts"].

PMID- 1398196
TI  - [Epidemiology of abortion. A one-year prospective study].
AB  - This study evaluates the epidemiological characteristics of patients attended at
      the Hospital Central Militar (Service of Obstetrics), who had diagnosis of
      abortion. The study was prospective and was conducted through one year. There
      were 316 cases of abortion (12.4%) among 2,550 obstetrical patients. The most
      frequent type of abortion was the incomplete one (58.6%). Only 38 (12.0%) women
      had an septic abortion. From an epidemiological point of view, patients with
      abortion were young (mean age 26.45 +/- 6.49 years); married (87.4%); with mean
      parity of 2.20 +/- 2.16; 26.3% of them had their first pregnancy and 78.2% had
      their first abortion. Abortion were more frequent between 9 and 12 weeks of
      pregnancy. After the 10th week, the D&C had more complications than before. The
      conclusion from this study is that in this group of population, abortion is not
      an important problem of health.

PMID- 1398197
TI  - [Correlation of creatine phosphokinase blood level with prenatal fetal heart rate
      as a prognostic factor in tissue hypoxia].
AB  - The presence of a high serum activity of the creatinine phosphokinase enzyme
      (CPK) could be the result of an hypoxic tissue event. The existence of an ominous
      fetal heart rate tracing is a reliable method which indicates the presence of an
      hypoxic state in variable degrees. Thirty-five pregnancies between 34 and 41
      weeks of gestation were prospectively studied to correlate both, CPK activity and
      cardiotocography, with perinatal morbidity and mortality. All the patients had
      antepartum fetal heart rate testing and pregnancy was terminated by cesarean
      section within seven days to the last fetal heart tracing. As soon as the baby
      was born, we took an umbilical cord sample to measure CPK activity and a second
      sample was also taken at 36 hours of life. All the neonates had pediatric,
      neurologic, electrocardiographic and sonographic evaluation within their 48 hours
      of extrauterine life. Two groups were created: Group A included 14 neonates with
      normal cardiotocographic tracings (control group) and Group B had 21 infants with
      abnormal tracings (study group). We found an elevated serum CPK activity with
      statistic significance in the next three conditions: a) In the sample at 36 hours
      of life when compared to the cord sample in the control group, p less than 0.001;
      b) In the neonatal sample at 36 hours of age when compared to the cord sample in
      the study group, p less than 0.001; c) In the neonates of the study group
      compared to the neonates of the control group at 36 hours of extrauterine life, p
      less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398198
TI  - [Laparoscopic findings during bilateral tubal obstruction].
AB  - During the period 1987 to 1990 at Hospital Luis Castelazo Ayala, IMSS, a
      prospective study was carried out. For this study 374 bilateral tubal
      obstructions (BTO) were included in interval of gestation by means of laparoscopy
      with silastic rings. The objective was to observe the status presented by the
      organs contained in the pelvic cavity of women considered healthy; so, as to
      present pathology, opportunely treat it. Main findings were: Pelvic adhesions 37
      cases (9.8%), uterine myomatosis 33 cases (8.8%), tubal pathology 18 cases
      (4.8%), ovarian cysts 11 cases (2.9%), and endometriosis 9 cases (2.4%). Global
      pathology was 108 cases (28.8%). The use of laparoscopy in BTO allows to find non
      expected pathology in apparently healthy women and offers them the opportunity of
      receiving treatment immediately, avoiding thus to attribute to BTO symptomatology
      that could be derived from existing pathology.

PMID- 1398200
TI  - [Nosocomial infection during puerperium].
AB  - Material and methods used to assess the epidemiology of puerperal infection (PI)
      in the National Institute of Perinatology (Mexico) between 1984 and 1990, are
      described. We observed that the general rate of PI ranged between 1.6 and 3.1;
      post-cesarean section posed a higher risk of infection than vaginal partum.
      Endometritis, associated with cesarean section, was the most frequent form of PI
      and gram positive flora was the most frequently found etiological agent. In
      general terms, we found that the rate of PI remained constant through the years
      of study, even when there was a significant increase in the practice of cesarean
      operations. Finally, we emphasize the need for the standardization of clinical
      norms used to assess the epidemiology of infection events. Standard norms will
      allow health-service institutions to compare results, observe tendencies, predict
      changes and take preventive actions.

PMID- 1398199
TI  - [Kallmann syndrome: report of a pregnancy case and review of the literature].
AB  - We report the case of a pregnancy in a patient with Kallmann's syndrome. The
      patient responded adequately to gonadotropin releasing hormone (GnRH) stimulation
      test, and after the third cycle of stimulation the patient became refractory to
      the treatment. The patient did not respond to exogenous follicle stimulating
      hormone (FSH) or human menopausal gonadotropins (hMG) for ovulation induction.
      For these reasons, we used a short course of leuprolide acetate (LUPRON) followed
      by hMG, which resulted in ovulation and a subsequent pregnancy which was carried
      to term. We present an alternate approach to ovulation induction in patients with
      Kallmann's syndrome and a review of the literature.

PMID- 1398201
TI  - [Radiotherapy of cancer of the endometrium. Analysis of 53 cases].
AB  - Fifty three patients with endometrial carcinoma received radiotherapy from 1986
      to 1987, at the Hospital de Oncologia Centro Medico Nacional. Radiotherapy was
      given preoperatively in five patients, postoperatively in thirty nine patients,
      and radical in nine cases. Obesity, Hypertension and Diabetes were present in
      60%. The patients have been in control from 3 to 44 months, with average of 18
      months. Diagnosis was realized for genital bleeding 45/53 (85%), and increased
      uterine size 6/53 (11%). There were stage I 24/53 (45%), stage II 13/53 (24%)
      patients. Non classified eight cases, five of them were without tumoral activity
      at initial valoration, and three had tumor present. We analyzed stage treatment
      utilized, correlated with morbidity, tumoral response, free survival. We
      concluded that staging surgery is effective to chose the type of treatment.

PMID- 1398202
TI  - [Tuberculosis in the pregnant woman].
AB  - The prevalence of tuberculosis (TB) in Mexico as in the rest of the developing
      countries is high and no reduction has been noted in the past years. This article
      describe the clinical features of the disease during the gestational period. We
      studied 15 cases of TB and pregnancy treated at the Infectious Diseases
      Department of the Instituto Nacional de Perinatologia, from January 1990 to June
      1991. At our Institute the incidence was 1.54 cases by 1000 obstetric patients
      discharged, with a lethality rate of 6.6 deaths by 100 infected patients. We
      treated 15 women, nine had pulmonary TB, three renal TB, two TB of the cervical
      lymph node and one cutaneous TB. In seven patients the diagnosis was made before
      pregnancy, other seven were diagnosed during gestation, and one during
      puerperium. All patients were treated with antituberculous drugs; the most
      frequent combination was isoniazid, ethambutol and rifampin. Twelve women had no
      complications, one died, another developed preeclampsia, and in one case the
      patient had a low birth weight neonate. No cases of congenital TB were identified
      and none of the neonates had abnormalities at birth.

PMID- 1398203
TI  - [Changes in glucose metabolism during pregnancy: hospital experience].
AB  - The clinical heterogeneity of Diabetes Mellitus (DM) is also evident during the
      gestational period and thus, pregnancy could be complicated by a previously
      diagnosed DM or by diabetes that is first diagnosed during pregnancy (gestational
      diabetes or gestational alteration of the oral glucose tolerance test according
      with the degree of hyperglycemia). Independently of the stage at time of maternal
      diagnosis, the conceptus is at greater risk (probably since the time of
      conception) for abortion, genetic malformations, perinatal metabolic
      complications and death; these risks are apparently directly related with the
      time at diagnosis, duration and degree of metabolic alteration on the mother
      (mainly hyperglycemia) and the adaptive mechanisms on the product
      (hyperinsulinemia). Retrospectively, 412 pregnancies complicated with any type of
      carbohydrate metabolism alteration were studied in our service. The results
      demonstrated a high frequency of Gestational diabetes (42.2%) and of type II
      diabetes (35.9%); there was a good agreement with previous reports regarding the
      personal and family histories in the patients already known diabetic before
      pregnancy. The types of obstetric complications were similar to previous reports,
      but some of them with a greater frequency in our patients, namely hydramnios,
      toxemia, and urinary tract infection, and ketoacidosis with a minor frequency. We
      also observed an increased frequency of congenital malformations on the products.
      On the other hand, the metabolic complications of the newborn were similar to
      other reports with a slight predominance on the babies of known diabetic mothers
      prior to gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398204
TI  - [Effect of primary ovarian insufficiency on the molecular heterogeneity of
      pituitary gonadotropins].
AB  - It is known that hypophysial gonadotropins circulate in different molecular forms
      which are provided with different biological activity and that the proportion of
      such varieties keep a relation with the concentrations of estrogens in
      circulation. In physiological menopause predominate the great molecular forms
      which have a lesser biological activity and when estrogens are administrated a
      change is produced to smaller molecular forms. The present study tries to
      determine if in cases of ovarian insufficiency of long duration as in precocious
      menopause and the syndrome of refractory ovary the chromatographic conduct of
      gonadotropin is similar. Six patients with precocious menopause, and three with
      the syndrome of refractory ovary, were studied, in order to make a comparison of
      chromatographic pattern of FSF and LH in serum, with the one found in women with
      normal ovarian function and with physiologic menopause. The chromatographic
      analysis was done by filtration in gel of the serum and the subsequent
      determination of LH and FSH by RIA of double antibody. It was found that the
      chromatographic pattern of patients with ovarian insufficiency of long duration,
      characteristically presents larger molecular forms, specially in the refractory
      ovary syndrome with a greater alteration in the profile of LH. With base on these
      results it is concluded that the duration of ovarian insufficiency determine the
      type of molecular form, predominant, of gonadotropins. Also it is suggested that
      for the syndrome of refractory ovary, the greater heterogenicity of gonadotropins
      may explain part of physiopathogeny.

PMID- 1398206
TI  - [Ovarian cancer (experience with 186 patients)].
AB  - An experience with 186 ovarian carcinomas seen at the Oncology Service of The
      General Hospital of Mexico, between 1981 to 1990 is reported. Fifty patients,
      (26.9%) were in stage I; 2, (1.0%) were in stage II; 113 in stage III, (60.7%)
      and 21, (11.2%) were in stage IV. Epidemiological and clinical aspects are
      reviewed as well as results of treatment. In 137 cases, (73.6%) we have follow up
      and it was without evidence of disease between 12 and 60 months with a mean of 18
      months in 32, (23.3%). This number includes 22 of 26 patients in stage I,
      (84.6%); 1 of 2 in stage II; 9 of 89, (10.1%) in stage III and 0 of 20 in stage
      IV. There were not significant differences in prognosis for stage I with the
      schemes of treatment employed: only surgery, postoperative radiotherapy and
      postoperative chemotherapy. Patients in stage III evolutioned without evidence of
      disease when the surgery left residual disease of 2 cms or less for unit: There
      were 1 of 59 patients treated only with surgery (1.6%); 3 of 15, (20%) treated
      with radiotherapy to whole abdomen plus over dosage to pelvis and 5 of 15,
      (33.3%) treated with two agents of chemotherapy. (cyclophosphamide plus
      adriamycin of cyclophosphamide plus cisplatin). In 3 of 11 stage III patients,
      (27.2%) with second look surgeries, we found macroscopic residual tumor.

PMID- 1398205
TI  - [Mechanism of action of steroid hormones. I. Estrogens].
AB  - The steroid hormone are very versatile molecules: although they are related among
      them by their chemical structure, they have very diverse functions and including
      antagonic. Their action mechanism is not completely cleared. The estrogens
      participate in the regulation of practically all the reproductive and sexual
      events of the female, although the intracellular actions by which they take place
      are not well known and the proposed models do not adequately satisfy the
      questions. Currently it is accepted the existence of a cytoplasmic and/or nuclear
      receptor, without explaining satisfactorily how the hormones come to the nucleus.
      The endocrine events that are rapidly expressed (seconds) are due to a possible
      interaction with cellular membrane. The purpose of this review is to analyze and
      concilliate the reported data on the mechanism of action of estrogens.

PMID- 1398207
TI  - [Premature membrane rupture: morbidity-mortality in pregnancies under 36 weeks].
AB  - The incidence of premature rupture of membranes in pregnancies of 36 weeks or
      less, in relation to the total births (3,796) is 1.3%; in relation to pregnancies
      less than 36 weeks (49 cases) 21.5%, and in pregnancies of less than 34 weeks (17
      cases) of 0.47%. Infectious mortality was 2.2%. There was no maternal mortality.
      Cesarean section incidence was 43%. Neonatal infectious morbidity was present in
      16.3%. Neonatal mortality on 4/30 cases was 13.0%; global mortality at two years
      was 5/30 cases, 17.0%.

PMID- 1398208
TI  - [Nifedipine in gynecology and obstetrics].
AB  - Nifedipine has both vasodilator and relaxant actions in arterial smooth muscle
      and other tissues, like uterus. The goal of this review is describe the potential
      uses of this calcium antagonist in two clinical features in pregnancy. First, in
      premature labor, nifedipine is an appropriate alternative related with beta
      mimetic or prostaglandin synthetase inhibitors agents, with good tocolytic
      properties and safe for both mother and baby. Second, in the treatment of
      hypertension in pregnancy or preeclampsia, where, according literature,
      nifedipine would be a valuable therapeutic gun. It is exposed the nifedipine
      advantages and disadvantages in pregnancy found by the authors from the reports
      reviewed here. It is analyzed the ethics of nifedipine use in pregnancy.
      Moreover, it is pointed out the nifedipine clinical usefulness in the treatment
      of primary dysmenorrhea and it is analyzed some nifedipine hemodynamic aspects on
      uterine blood flow.

PMID- 1398209
TI  - [Report of a case of deferred abortion in cervical pregnancy].
AB  - A patient with cervical pregnancy by clinical and ultrasonographic criteria
      underwent cervical and uterine curettage without complications. The histological
      study showed hyalinized corial villous with inflammatory infiltration and the
      material from uterine cavity showed decidual changes. The spontaneous and
      previous embryo death induce a scanty bleeding following curettage and thus,
      corroborate in a natural way the efficacy of any substance used to desvitalize
      the pregnancy and in consequence, diminish the vascular blood flow before
      evacuation in order to get a good result following conservative management.

PMID- 1398210
TI  - [Quantification of deoxyribonucleic acid and collagen as biological markers in
      uterine leiomyoma].
AB  - The uterine leiomyomas (UL) are tumors compound by smooth muscle connective
      tissue. Growth depends mainly of two basic mechanisms: hypertrophy of myometrial
      cells and connective tissue deposit. The quantification of the basic elements of
      the tumor permits to try its application as biochemical markers of disease,
      auxiliary diagnostic criteria, or in medical therapeutical monitorization,
      alternative that lately has become very important. In the present study 33
      patients are included, in two groups. Group I women with uterine leiomyomatosis
      (n = 17) and Group II (n = 16) without UL. A prospective, double blind,
      transversal of cases and control study. Connective tissue concentration was
      evaluated based on collagen determination. The evaluation of muscular tissue was
      done by desoxyribonucleic acid (DNA) measurement. The results showed a
      significant increase in connective tissue concentration (until 500%) and a
      significant diminution of cellularity (DNA) in women with UL, as compared with
      control group. The main biochemical and clinical implications of these findings,
      are commented upon.

PMID- 1398211
TI  - [National Congress of Gynecology and Obstetrics. 27 September--2 October 1992.
      Abstracts].

PMID- 1398212
TI  - In memoriam Trevor Frank Slater (1931-1992).

PMID- 1398213
TI  - Human plasma lipid peroxide levels show a strong transient increase after
      successful revascularization operations.
AB  - This study was performed to evaluate the hypothesis that oxygen radicals/lipid
      peroxidation are involved in reperfusion injury in humans. The study included 37
      patients, who underwent surgical revascularization operations for kidney
      transplantation (9 subjects) or limb salvage (28 subjects). Peripheral venous
      blood samples were taken 30 min before starting reperfusion (baseline) and 1, 2,
      3, 4, and occasionally 6 to 18 h after revascularization. The amount of plasma
      malonaldehyde formed in the reaction with thiobarbituric acid (MDA-TBA) was
      determined by high-performance liquid chromatography (HPLC). The baseline MDA-TBA
      values of the patients were very close to the value determined for 20 age-matched
      healthy subjects (i.e. mean +/- SD 0.689 +/- 0.294 nmol/mL plasma [range 0.2 to
      1.37] vs. 0.700 +/- 0.209 nmol/mL plasma [range 0.385 to 1.29]). All patients
      responded to successful revascularization with significant increase of the plasma
      MDA-TBA within about 1 h after onset of reperfusion. Thereafter the values
      decreased nearly to the preoperative state. The mean increase of MDA-TBA was 107%
      in kidney transplantation and 54% in limb revascularization. In a few patients
      with severe arteriosclerosis, revascularization was not optimal and no increase
      in the MDA-TBA value occurred. The results of this study indicate that
      therapeutic intervention to prevent lipid-peroxidation-mediated reperfusion
      injury is confined to a rather narrow time window and must be undertaken either
      prior to or immediately after revascularization.

PMID- 1398214
TI  - Selection and analysis of superoxide dismutase mutants of Neurospora.
AB  - A survey of 12 genetically distinct, heat-sensitive mutants of Neurospora
      revealed three (un-1, un-3, and un-17) that are specifically deficient in the
      superoxide dismutase (SOD) isozymes SOD-2 (mitochondrial), SOD-3 (mitochondrial),
      SOD-4 (exocellular), respectively. Genetic analysis of the three mutants
      indicates that the enzyme deficiencies are probably the cause of the heat
      sensitive phenotype. The phenotypes of the mutants are (1) no growth at the
      normally optimal temperature 35 degrees C and comparatively inferior growth at 15
      30 degrees C; (2) inferior resistance to the oxidants paraquat or oxygen; (3)
      female sterility; and (4) inferior conidial viability and longevity. Paraquat or
      O2 inhibition is alleviated respectively by desferrioxamine-Mn (a SOD mimic) and
      tocopherol. Diverse antioxidants, including tocopherol, are therapeutic for the
      heat-sensitive and female-sterile phenotypes, and for inferior growth of wild
      type at stressfully high temperatures. The results support previous theories that
      heat stress is a form of oxyradical/oxidant stress and that antioxidant enzymes
      such as SOD are essential for normal growth, development, and longevity. Since
      the three genes may encode the three enzymes and are not closely linked to either
      one another or the family of antioxidant-enzyme regulatory genes Age-1, the
      latter apparently trans-regulate their expression.

PMID- 1398215
TI  - Formation of hydrogen peroxide by lens proteins: protein-derived hydrogen
      peroxide as a potential mechanism of oxidative insult to the lens.
AB  - The exposure of dialyzed preparations of lens crystallins to copper (II) ions
      causes a decrease in protein surface thiol and the production of hydrogen
      peroxide (H2O2). H2O2 production by gamma and beta crystallin subfractions (which
      contain the greatest level of thiol) is the predominant source of this H2O2.
      Protein surface thiols are probable sources of H2O2 formation since N-ethyl
      maleimide treatment of lens proteins and zinc ions inhibit H2O2 production. These
      data are consistent with a hypothesis that transition metal-catalyzed oxidation
      of protein contributes to cataractogenic lens protein oxidations.

PMID- 1398216
TI  - Brown fat thermogenesis and exercise: two examples of physiological oxidative
      stress?
AB  - Both brown fat tissue (BAT) and skeletal muscle experience large increases of
      oxygen consumption and oxygen radical generation during activation. This,
      together with the relatively low activities of antioxidant enzymes in these two
      tissues and the high lipid content and free fatty acid liberation of BAT, can
      produce a physiological oxidative stress. Increases of in vivo or in vitro (BAT)
      lipid peroxidation have been described in these tissues after activation. They
      react to this oxidative stress in an adaptive way after chronic stimulation. Cold
      acclimation increases antioxidant enzymes, ascorbate, and especially reduced
      glutathione (GSH) in BAT. There is controversy about the variations of
      antioxidants in skeletal muscle after acute exercise. Nevertheless, exercise
      training seems to increase muscle antioxidant enzymes and GSH. Many reports show
      that vitamin E levels decrease in the muscle and increase in plasma during
      exercise. Studies of vitamin E deficiency and supplementation strongly suggest
      that this vitamin is of protective value during exercise.

PMID- 1398217
TI  - The role of lipid peroxidation and antioxidants in oxidative modification of LDL.
AB  - The purpose of this study is to provide a comprehensive survey on the
      compositional properties of LDL (e.g., lipid classes, fatty acids, antioxidants)
      relevant for its susceptibility to oxidation, on the mechanism and kinetics of
      LDL oxidation, and on the chemical and physico-chemical properties of LDL
      oxidized by exposure to copper ions. Studies on the occurrence of oxidized LDL in
      plasma, arteries, and plaques of humans and experimental animals are discussed
      with particular focus on the use of poly- and monoclonal antibodies for
      immunochemical demonstration of apolipoprotein B modifications characteristic for
      lipid peroxidation. Apart from uptake of oxidized LDL by macrophages, studies
      describing biological effects of heavily or minimally oxidized LDL are only
      briefly addressed, since several reviews dealing with this subject were recently
      published. This article is concluded with a section on the role of natural and
      synthetic antioxidants in protecting LDL against oxidation, as well as some
      previously unpublished material from our laboratories.

PMID- 1398218
TI  - Biochemical and toxicological properties of the oxidation products of
      catecholamines.
AB  - The normal catabolism of catecholamines proceeds through enzymatic pathways
      (monoaminooxidase, catechol-o-methyltranserase, and phenolsulphotransferase). In
      addition, nonenzymatic oxidative pathways might take place since catechols are
      readily oxidized. In this review article, the pathways of formation of the
      oxidation products of catecholamines and their reactions are described. The
      interactions of these products with different biological systems and their
      toxicity are examined. Among the reactions known to occur is that with
      sulfhydryls, which results in either a covalently linked adduct or disulfide
      production. Another interesting pathway to toxicity involves the oxidation of
      these catecholamine products by oxygen, with the formation of damaging oxygen
      derived species. The action of the oxidation products of catecholamines is
      outlined, with special attention to the nervous and cardiac systems.

PMID- 1398219
TI  - Protection by beta-carotene and related compounds against oxygen-mediated
      cytotoxicity and genotoxicity: implications for carcinogenesis and
      anticarcinogenesis.
AB  - beta-Carotene protects against photooxidative dermatitis in porphyric humans and
      mice by quenching of photoactivated species. Other actions of beta-carotene in
      vivo are explained on the basis of its ability to scavenge free radicals in
      vitro. For example, in guinea pigs treated with CCl4, beta-carotene decreases
      pentane and ethane production. Epidemiological studies link low serum beta
      carotene levels to elevated risk of lung and other cancers, and in intervention
      trials, beta-carotene diminishes preneoplastic lesions. However, the
      dose/response relationships are not well established, and antineoplastic
      mechanisms await clarification. Given a radical quenching mechanism, beta
      carotene should block tumor promotion, but more typically the site of action is
      progression and an even later role in invasion has not been ruled out. Some
      antineoplastic actions of carotenoids (such as increased rejection of
      fibrosarcomas in mice) are attributed to immunoenhancement; others may reflect
      conversion to retinoids and subsequent gene regulation. Carotenoids other than
      beta-carotene may act at an earlier stage of carcinogenesis or be more effective
      as anticarcinogens at certain target sites. As scavengers of hydroxyl radicals,
      canthaxanthin and astaxanthin are more effective than beta-carotene.
      Canthaxanthin is sometimes more effective than beta-carotene in chemoprevention,
      but it is sometimes completely ineffective. Lycopene quenches singlet oxygen more
      than twice as effectively as beta-carotene. However, the antineoplastic actions
      of lycopene or astaxanthin remain untested. Explorations of the interactions of
      carotenoids with other nutrients are just beginning. Dietary fat increases
      absorption of carotene but decreases antineoplastic effectiveness. Research is
      hampered by technical problems, including the unavailability of rigorous
      controls, the instability of carotenoids, and the heterogeneous phase structure
      induced by hydrophobic compounds in aqueous media. Areas of current controversy
      and promising approaches for future research are identified.

PMID- 1398220
TI  - Antioxidant potential of ferulic acid.
AB  - Ferulic acid is a ubiquitous plant constituent that arises from the metabolism of
      phenylalanine and tyrosine. It occurs primarily in seeds and leaves both in its
      free form and covalently linked to lignin and other biopolymers. Due to its
      phenolic nucleus and an extended side chain conjugation, it readily forms a
      resonance stabilized phenoxy radical which accounts for its potent antioxidant
      potential. UV absorption by ferulic acid catalyzes stable phenoxy radical
      formation and thereby potentiates its ability to terminate free radical chain
      reactions. By virtue of effectively scavenging deleterious radicals and
      suppressing radiation-induced oxidative reactions, ferulic acid may serve an
      important antioxidant function in preserving physiological integrity of cells
      exposed to both air and impinging UV radiation. Similar photoprotection is
      afforded to skin by ferulic acid dissolved in cosmetic lotions. Its addition to
      foods inhibits lipid peroxidation and subsequent oxidative spoilage. By the same
      mechanism ferulic acid may protect against various inflammatory diseases. A
      number of other industrial applications are based on the antioxidant potential of
      ferulic acid.

PMID- 1398221
TI  - Reduction of sperm whale ferrylmyoglobin by endogenous reducing agents: potential
      reducible loci of ferrylmyoglobin.
AB  - The reactivity of the endogenous antioxidants ascorbate, ergothioneine, and urate
      toward the high oxidation state of sperm whale myoglobin, ferrylmyoglobin-formed
      upon oxidation of metmyoglobin by H2O2--was evaluated by optical spectroscopy and
      SDS-PAGE analysis. Depending on whether these antioxidants were present in the
      reaction mixture before or after the addition of H2O2 to a metmyoglobin
      suspension, two different effects were observed: (a) In the former instances,
      ascorbate, ergothioneine, and urate reduced efficiently the oxoferryl moiety in
      ferrylmyoglobin to metmyoglobin and prevented dimer formation, a process which
      requires intermolecular cross-link involving specific tyrosyl residues. In
      addition, all the reducing compounds inhibited--albeit with different
      efficiencies--dityorosine-dependent fluorescence build up produced via
      dimerization of photogenerated tyrosyl radicals. (b) In the latter instances, the
      antioxidants reduced the preformed sperm whale ferrylmyoglobin to a modified
      metmyoglobin, the spectral profile of which was characterized by a blue shift of
      the typical 633 nm absorbance of native metmyoglobin. In addition, under these
      experimental conditions, the antioxidants did not affect dimer formation, thus
      indicating the irreversible character of the process. The dimeric form of sperm
      whale myoglobin--separated from the monomeric form by gel electrophoresis of a
      solution in which ergothioneine was added to preformed ferrylmyoglobin--revealed
      optical spectral properties in the visible region identical to that of the
      modified myoglobin. This suggests that the dimeric form of the hemoprotein is
      redox active, inasmuch as the oxoferryl complex can be reduced to its ferric
      form. These results are discussed in terms of the potential reactivity of these
      endogenous antioxidants toward the reducible loci of ferrylmyoglobin, the
      oxoferryl moiety, and the apoprotein radical.

PMID- 1398222
TI  - The British Society of Gastroenterology, 1992 annual meeting. 9-11 September
      1992. Abstracts.

PMID- 1398224
TI  - Helicobacter pylori secretes a chemotactic factor for monocytes and neutrophils.
AB  - Helicobacter pylori is associated with an inflammatory reaction in the stomach
      and duodenum, yet the mechanism of this inflammatory infiltrate is unknown. The
      ability of Helicobacter pylori to secrete a factor that attracts leucocytes is
      investigated. Helicobacter pylori conditioned supernatant attracted neutrophils
      and monocytes with 50-100% of the activity of control chemotactic factor, 10(-8)
      M formyl-methionine-leucine-phenylalanine. Strains derived from individuals with
      ulcer or non-ulcer associated H pylori infections displayed similar chemotactic
      activity. Preliminary characterisation shows that the factor has a molecular
      weight of less than 3000, is heat stable, is acid resistant, and can be diluted
      at least 10-fold. Checkerboard analysis confirmed that the activity was
      chemotactic rather than chemokinetic. This chemotactic activity could play a role
      in the pathogenesis of Helicobacter pylori gastritis.

PMID- 1398223
TI  - Five year prospective study of the incidence, clinical features, and diagnosis of
      achalasia in Edinburgh.
AB  - With the increasing availability of manometry, patients with achalasia are often
      referred at an early stage when they lack the classic features of established
      disease. A prospective five year study of the presenting features of untreated
      achalasia referred to our department was undertaken. Twenty men and 18 women
      presented throughout adult life, with a mean age at the time of diagnosis of 44
      years (range 17 to 76 years). The presenting symptoms were dysphagia: for solids
      (100%) and for liquids (97%), chest pain (74%), and weight loss (60%). Endoscopy
      was reported as normal in 15 patients and achalasia was suggested in only 21 of
      33 barium examinations. Fourteen had been treated for gastrooesophageal reflux
      but none had been misdiagnosed as having cardiac or psychiatric disease. The
      annual incidence of achalasia in the Lothian region is 0.8/100,000 of population.
      Persistent dysphagia is the cardinal symptom of achalasia which presents
      throughout adult life. Nevertheless, recent onset achalasia is often misdiagnosed
      as gastrooesophageal reflux disease. Because endoscopy is frequently normal and
      the diagnosis is often not made by radiology, manometric investigation is
      necessary if the condition is to be recognised and treated at an early stage.

PMID- 1398225
TI  - Effect of Helicobacter pylori infection on 24 hour intragastric acidity in
      patients with gastritis and duodenal ulcer.
AB  - Helicobacter pylori status, gastric histology, and 24 hour acidity were studied
      in 35 gastritis patients, 21 duodenal ulcer patients, and 14 subjects with normal
      gastric mucosa. H pylori was identified in 21 of 35 patients with chronic active
      gastritis and in 19 of 21 duodenal ulcer patients, but in none of those with
      normal gastric mucosa. Mean scores of activity of gastritis were similar in H
      pylori positive gastritis and duodenal ulcer patients, but were significantly
      lower in H pylori negative gastritis patients (2.1 (0.8) and 2.3 (0.9) v 1.4
      (0.7); p < 0.01, respectively). Median 24 hour hydrogen ion activity
      (interquartile range) was 21 (8.9-38.0) mmol/l in normal subjects and 23 (11.2
      49.0) mmol/l, 19 (7.1-33.1) mmol/l, 44 (25.1-63.1) mmol/l, and 36 (31.6-39.8)
      mmol/l respectively in gastritis and duodenal ulcer patients with and without H
      pylori infection. During all predefined time periods, intragastric acidity was
      significantly higher in patients with H pylori positive duodenal ulcers compared
      with gastritis patients and normal subjects. However, there was no significant
      difference in intragastric acidity between the H pylori positive and negative
      gastritis patients. These results suggest that most of the subjects with chronic
      H pylori infection have normal gastric acidity.

PMID- 1398226
TI  - Helicobacter pylori and gastric cancer: correlation with gastritis, intestinal
      metaplasia, and tumour histology.
AB  - This study aimed to examine the association between Helicobacter pylori,
      histological gastritis, and intestinal metaplasia in gastric cancers of different
      histological types. A total of 169 gastrectomy specimens received in one
      pathology department were studied. Altogether 156 were adenocarcinomas
      (intestinal type 87, diffuse type 50, mixed type 19). Gastritis occurred in 137
      of 163 body specimens (84%) and in 126 of 131 antral specimens (96%). Its
      presence was unrelated to tumour histology. Atrophic gastritis was more common in
      both body and antral mucosa in intestinal type compared with diffuse type
      carcinoma. This was also true for intestinal metaplasia of the body, but not of
      the antral mucosa. H pylori was present in 101 of 163 (62%) body specimens and 56
      of 131 (43%) antral specimens. In intestinal type carcinoma, H pylori was found
      in 52/84 (62%) body specimens and in 24/70 (34%) antral specimens, while the
      corresponding figures for diffuse type carcinoma were 29/48 (60%) and 17/38 (45%)
      respectively. Tumour histology therefore had no influence on the occurrence of H
      pylori. Tumour site had no effect on the presence or absence of gastritis,
      atrophic changes, intestinal metaplasia, or H pylori. While both H pylori and
      gastritis are associated with gastric cancer, the association is unrelated to
      tumour histology and may not be a causal one.

PMID- 1398227
TI  - Oncogenes and onco-suppressor gene in adenocarcinoma of the oesophagus.
AB  - While the activation of the proto-oncogenes has been implicated in the
      development and progression of cancer of many tissues, the role of oncogenes in
      the development of oesophageal adenocarcinoma has not been defined. Fifteen
      patients who had undergone resection for oesophageal adenocarcinoma and 15 who
      had undergone oesophagectomy or biopsy for Barrett's oesophagus were studied. The
      latter patients also had adjacent normal gastric mucosa biopsied for comparison
      with the metaplastic oesophageal mucosa. The mucosal samples were snap frozen and
      subsequently stained with monoclonal antibodies to the following oncogene
      associated proteins; c-erbB2 (neu and CE-1) (external domain), c-erbB2 (NCL-CB11)
      (internal domain), c-src, c-ras, c-myc, c-fos, c-jun, and the onco-suppressor
      gene--p53. All tumours were well or moderately differentiated adenocarcinomas
      arising from the lower third of the oesophagus. Eleven specimens showed strong
      membraneous staining with both c-erbB2 (neu) and c-erbB2 (CBL-CB11). Seven
      specimens showed strong nuclear staining with p53 onco-suppressor gene. Three
      specimens were positive for c-ras and c-src, and two were positive for c-jun. In
      Barrett's epithelium, nine specimens were positive for c-erbB2 (neu and CB11),
      three were positive for c-src, two were positive for c-ras and c-jun, and one was
      positive for c-fos. Two of the gastric mucosal biopsy specimens expressed c-erbB2
      weakly but no other oncogenes were found. The frequency of positive staining for
      c-erbB2 is very high, compared with the expression of these genes in other
      tumours. It is also concluded that errors in the onco-suppressor gene p53, and
      especially in the external and internal domains of c-erbB2, which is also often
      expressed in Barrett's mucosa, may be implicated in the development of
      adenocarcinoma of the oesophagus.

PMID- 1398228
TI  - Gastric mucosal barrier: barrier to hydrogen ions imparted by gastric surfactant
      in vitro.
AB  - A simple experiment is described which shows how the highly surface active
      ingredient of gastric surfactant (DPPC) can be deposited on a filter paper to
      reduce the rate of transmission of hydrogen ions by one to two orders of
      magnitude. This finding is compatible with previous studies implying that the
      hydrophobic layer of surface active phospholipid provides the gastric mucosal
      barrier as a distinct physical entity.

PMID- 1398229
TI  - Correlation between echographic gastric emptying and appetite: influence of
      psyllium.
AB  - The correlation between ultrasonographic gastric emptying and appetite was
      studied. Echographic evaluation of gastric emptying by measurement of the antral
      vertical diameter and assessment of sensations of hunger and satiety using
      analogue visual scales were performed simultaneously in 12 healthy volunteers.
      Measurements were carried out after the intake of 10.8 g psyllium or placebo in a
      randomised, crossover, double blind trial. The correlation between echographic
      gastric emptying and sensations of hunger and satiety was excellent (p < 0.001)
      after the intake of either psyllium or placebo. Psyllium significantly delayed
      gastric emptying from the third hour after a meal. It increased the sensation of
      satiety and decreased hunger at the sixth hour after the meal. The association
      between echographic measurement and visual scales is a simple method of
      evaluating the relationship between the stomach and appetite. The pharmacodynamic
      effect of psyllium should be confirmed by longterm therapeutic trials.

PMID- 1398230
TI  - Cryptosporidium, chronic diarrhoea and the proximal small intestinal mucosa.
AB  - The association between Cryptosporidium, chronic diarrhoea and a proximal small
      intestinal mucosal enteropathy was reviewed over a six and a half year period.
      One hundred and twenty three children with cryptosporidiosis and no clinical
      evidence of immune deficiency were identified. 50% of children excreting only
      Cryptosporidium had chronic diarrhoea. Most cases (63%) of chronic diarrhoea
      occurred in the first two years of life. A mild to moderate enteropathy was
      present in all nine children undergoing a small intestinal biopsy and seven
      showed the presence of Cryptosporidium adhering to villous epithelium. All
      patients eventually recovered spontaneously. Cryptosporidium is a cause of
      chronic diarrhoea and a proximal small intestinal mucosal enteropathy in children
      without immune deficiency. Screening for the parasite should be part of the
      investigative procedures in children with chronic diarrhoea.

PMID- 1398231
TI  - Antibodies to Saccharomyces cerevisiae in patients with Crohn's disease and their
      possible pathogenic importance.
AB  - Saccharomyces cerevisiae (baker's yeast) may play an important part in the
      pathogenesis of Crohn's disease. Because of this the levels of IgG and IgA
      antibodies against three S cerevisiae strains (NCYC 77, NCYC 79, and NCYC 1108)
      were assayed in 49 patients with Crohn's disease, 43 with ulcerative colitis, 14
      with coeliac disease, and 21 healthy controls. Coded serum samples were tested by
      ELISA. Similar antibody patterns to all three strains were found. IgG and IgA
      antibody levels were significantly raised in patients with Crohn's disease
      compared with healthy controls (p < 0.001 and p < 0.0001 respectively) and with
      ulcerative colitis patients (p < 0.0001 and p < 0.0006 respectively). Raised IgA,
      but not IgG, yeast antibody levels were found in two patients with Crohn's
      disease who were intolerant to yeast, but these values were similar to those in
      other patients without yeast intolerance. In ulcerative colitis, both IgG and IgA
      levels were similar to normal controls. Patients with small bowel Crohn's disease
      had significantly higher IgG antibody levels than those with colonic disease (p <
      0.01). High levels of IgG, but not IgA, antibody were present in patients with
      coeliac disease, the antibody responses being indistinguishable from those found
      in Crohn's disease. It is concluded that the presence of IgG antibody to S
      cerevisiae is characteristic but not specific to Crohn's disease. Although raised
      IgA antibody levels are more frequently found in Crohn's disease, their
      pathogenic importance remains to be established.

PMID- 1398232
TI  - Epidemiological study of abdominal tuberculosis among Indian migrants and the
      indigenous population of Leicester, 1972-1989.
AB  - A retrospective, epidemiological study of abdominal tuberculosis in the city of
      Leicester from 1972 to 1989 is reported. Potential cases were identified from
      hospital medical records and endoscopy lists, in addition to the county
      notification register. The city population of 280,000 included over 75,000 South
      Asians. There were 146 cases among South Asians and six in Europeans, four of
      whom were British. The standardised incidence of abdominal tuberculosis in South
      Asians decreased significantly from 22.3 cases/10(5)/year during the 1970s to 9.2
      cases/10(5)/year in the 1980s (chi 2 = 42, p < 0.001). The incidence during the
      1980s was 10.7/10(5)/year in Hindus, 8.7/10(5)/year in Sikhs, and 4.6/10(5)/year
      in Muslims. The relative risk to Hindus was 2.3 fold greater, and for Sikhs 1.9
      fold greater, than that for Muslims, a finding similar to that in pulmonary
      tuberculosis. The standardised incidence in Europeans was 0.2/10(5)/year and they
      had significantly less abdominal tuberculosis than South Asians (Z = 8.6, p <
      0.001 and relative risk = 46). The standardised mortality ratio was significantly
      increased in Europeans (standardised mortality ratio = 755, 95% confidence
      interval 90-2730, chi 2 = 11.4, p < 0.001), but not in South Asians (standardised
      mortality ratio = 68, 95% confidence interval 20-160). Resection rates were
      similar between the two ethnic groups. Abdominal tuberculosis still occurs among
      migrants, and clinicians should remain alert to this in South Asians.

PMID- 1398233
TI  - Epithelial cells bearing class II molecules stimulate allogeneic human colonic
      intraepithelial lymphocytes.
AB  - HLA-DR+ gut epithelial cells may present antigen to intraepithelial lymphocytes
      (IEL). This study aimed to isolate an IEL population from the human colon to
      activate CD3 + IEL by a human colonic epithelial cell line (HT-29), bearing
      different concentrations of class II antigen (HLA-DR). IEL were isolated by a
      mechanical method from six patients with ulcerative colitis (UC) and from 14
      control patients. IEL were cocultured with HT-29 which had been induced to
      express class II molecules by gamma-interferon (IFN-gamma) in a dose dependent
      manner. The phenotype and the subsequent expression of activation markers by the
      IEL were determined to two colour flow cytometry. The IEL population had a
      CD4/CD8 ratio similar to that seen in tissue sections. In the mixed cell culture,
      the degree of IEL activation showed a positive correlation with the degree of HLA
      DR expression by the HT29 cells and the IEL secreted a IFN-gamma like factor that
      in turn stimulated the HT-29. Thus, depending on their expression of HLA
      molecules, colonic epithelial cells are able to activate CD3+CD8+IEL.

PMID- 1398234
TI  - Antiviral effect of prolonged intermittent lymphoblastoid alpha interferon
      treatment in chronic hepatitis B.
AB  - In a European multicentre study 40 patients with HBeAg positive chronic hepatitis
      B virus (HBV) infection were treated with 5 mega units of lymphoblastoid alpha
      interferon daily according to the following regimen: a four week primer course,
      four weeks of rest and a second course lasting 16 to 30 weeks. After 52 weeks of
      follow up, a response (HBeAg seroconversion and HBV-DNA negativity) was observed
      in 22 patients (55%). HBsAg seroconversion occurred in five patients (12.5%). One
      patient exhibited a relapse for serum HBeAg and HBV-DNA after cessation of
      treatment. According to a response prediction model, the observed response rate
      was not related to the selection of patients likely to respond. The initial
      interferon course induced a reduction of the serum HBV-DNA and HBeAg levels of
      87% and 18%, respectively, leading to a significantly lower level of viral
      replication activity at the start of the second longterm course compared with
      baseline. After 24 weeks of follow up (week 16 of the second course), 19 (48%)
      patients exhibited a response, 13 (32%) a partial response (HBeAg < 50% of
      initial level or HBV-DNA negative) and 8 (20%) no response. For eight of the 13
      partial responders treatment was stopped at week 24 and viral replication
      rebounded to pretreatment values. In the last five partial responders
      prolongation of therapy up to week 38 led to a definite response and HBsAg
      seroconversion in three of the five patients. The results of this study suggest
      that a short primer course and prolongation of therapy may help to enhance the
      response rate of alpha-interferon therapy for chronic hepatitis type B.

PMID- 1398236
TI  - Raised urea clearance in cirrhotic patients with high uric acid clearance is
      related to low salt excretion.
AB  - In cirrhotic patients without renal failure, salt retention could result from a
      decreased effective intravascular volume or could be a primary event leading to
      increased intravascular volume. Clearance of urea and uric acid depend on an
      effective intravascular volume. In the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH)--a state of increased intravascular volume--uric
      acid clearance is increased and that of urea is increased only when salt
      excretion is low. The intravascular volume of 60 consecutive cirrhotic patients
      without renal failure was estimated indirectly by studying the relationship
      between fractional excretion of filtered (FE) sodium, urea, and uric acid. Forty
      five per cent had a high FE uric acid (> 12%), which could mean a high
      intravascular volume, and presented with an FE urea that was inversely correlated
      with FE sodium (r = 0, 62; p < 0.001) as in SIADH, while in the controls the FE
      urea was positively correlated with FE sodium (r = +0, 46; p < 0.01). In patients
      who had a normal FE uric acid and low FE sodium (< 0.2%), the FE urea was
      significantly lower (40 (13)%, n = 20) than in subjects with high FE uric acid
      and a low FE sodium (61 (9)%, n = 16, p < 0.001); this last group also presented
      with lower mean blood urea concentrations (3.1 (1.2) mmol/l and 4.0 (1.8) mmol/l;
      p < 0.05) and a lower supine renin activity (p < 0.01). As observed in the SIADH,
      cirrhotic patient with high FE uric acid have raised FE urea only when salt
      excretion is low. It is believed that the low salt excretion is not caused by a
      decrease in effective intravascular volume and that this is increased in
      cirrhotic patients with raised FE uric acid.

PMID- 1398235
TI  - Effects of ethanol, acetaldehyde and cholesteryl esters on pancreatic lysosomes.
AB  - Recent studies indicate that altered lysosomal function may be involved in the
      early stages of pancreatic injury. Chronic consumption of ethanol increases rat
      pancreatic lysosomal fragility. The aim of this study is to determine whether the
      lysosomal fragility observed after chronic ethanol consumption is mediated by
      ethanol per se, its oxidative metabolite acetaldehyde or cholesteryl esters
      (substances which accumulate in the pancreas after ethanol consumption).
      Pancreatic lysosomes from chow fed rats were incubated for 30 minutes at 37
      degrees C with ethanol, acetaldehyde or phosphatidylcholine vesicles containing
      cholesteryl oleate. Lysosomal stability was then assessed by determination of:
      (a) Latency--that is, the per cent increase in lysosomal enzyme activity after
      addition of Triton X-100 and (b) Supernatant activity--that is, the proportion of
      lysosomal enzyme remaining in the supernatant after resedimentation of lysosomes.
      Acid phosphatase, N-acetyl glucosaminidase, beta-glucuronidase and cathepsin B
      were assayed as lysosomal marker enzymes. Lysosomes incubated with homogenising
      medium alone or equivalent volumes of phosphatidylcholine vesicles without
      cholesteryl oleate were used as controls. Cholesteryl oleate at concentrations of
      15 and 20 mM increased pancreatic lysosomal fragility as shown by decreased
      latency and increased supernatant enzyme. In contrast, ethanol (150 mM) and
      acetaldehyde (5 mM) had no effect on lysosomal stability in vitro. These results
      suggest that increased pancreatic lysosomal fragility observed with ethanol may
      be mediated by cholesteryl ester accumulation rather than by ethanol or
      acetaldehyde.

PMID- 1398237
TI  - Mucus glycoprotein biosynthesis in the human gall bladder: inhibition by aspirin.
AB  - Aspirin, which inhibits mucin secretion in the gastrointestinal tract prevents
      gall stone formation in animals and may reduce gall stone recurrence in man. This
      study examines the effect of aspirin on mucin synthesis in human gall bladder
      explants. Two hundred explants were cultured with 3H-glucosamine (74 kBq/ml) for
      24 hours at 37 degrees C. Mucin and other glycoproteins were isolated by papain
      digestion (72 hours) and exhaustive dialysis (144 hours) to remove non
      incorporated radioactivity and digested protein. 3H-glucosamine was readily
      incorporated into glycoprotein. Pooled gall bladder explants were fractionated on
      a CsCl density gradient and by gel filtration on Sepharose 2B and 4B to confirm
      that >90% radioactivity was incorporated into mucin. Acetylsalicylic acid (230
      666 micrograms/ml) significantly reduced total 3H-glucosamine incorporation (43
      89%), p<0.01 (unpaired t test). Diclofenac (125-1250 micrograms/ml), similarly
      reduced incorporation by 45-97% p<0.001 (unpaired t test). Inhibition of mucin
      glycoprotein biosynthesis was irreversible with both drugs. Analysis of pooled
      samples on Sepharose 4B showed abolition of radioactive incorporation into mucin
      but no effect on incorporation into low molecular weight glycoprotein material
      (10% of total incorporation). This study provides a method for measuring human
      gall bladder mucin synthesis and shows its irreversible inhibition by
      acetylsalicylic acid and diclofenac at concentrations compatible with a
      therapeutic dose.

PMID- 1398239
TI  - Postoperative bile leakage: endoscopic management.
AB  - Bile leakage is an infrequent but serious complication after biliary tract
      surgery. This non-randomised single centre study evaluated the endoscopic
      management of this problem in 55 consecutive cases. Treatment consisted of
      standard sphincterotomy and, if needed, subsequent stone extraction with or
      without endoprosthesis placement. The aim of all treatments was to facilitate
      bile flow into the duodenum. The biliary tract and the site of the leakage were
      visualised during endoscopic retrograde cholangiopancreatography (ERCP) in 98%.
      There was distal obstruction in 33--caused by retained gall stones in 15 patients
      and concomitant strictures in 18. Overall, 48 of 55 patients were treated
      endoscopically. An excellent outcome (clinical and radiological resolution of the
      bile leak) was achieved in 43 patients (90%). Five patients (10%) had continuing
      sepsis from which they died. Postoperative bile leakage can be diagnosed safely
      and effectively by ERCP and subsequent endoscopic management is successful in
      most cases.

PMID- 1398238
TI  - Inhibition of human gall bladder mucus synthesis in patients undergoing
      cholecystectomy.
AB  - Hypersection of gall bladder mucus is associated with gall stone formation in
      animal models. Aspirin inhibits both mucus synthesis and secretion, prevents gall
      stone formation in animals and reduces gall stone recurrence in man after
      dissolution therapy. Mucus biosynthesis in human gall bladder mucosal explants is
      inhibited by aspirin in vitro. We have studied the effects of aspirin in vivo.
      Fifty five patients with functioning gall bladder and stones have been
      randomised, 27 to group 1 (aspirin EC 300 mg once daily for seven days before
      cholecystectomy) and 28 to group 2 (controls). Gall bladder bile composition was
      analysed and mucus synthesis rates measured using 3H-glucosamine incorporation
      into mucosal explants cultured for 24 hours. Patient age, sex, and gall bladder
      histology were similar in both groups. There were no differences in stone
      composition, gall bladder bile calcium concentration, cholesterol saturation and
      cholesterol nucleation time. The mean 3H-glucosamine incorporation in aspirin
      treated patients was 1347 fmol/g wet weight as compared with 2008 fmol/g wet
      weight in controls (95% confidence interval 222-1100, p<0.005, unpaired t test).
      This reduction in biosynthesis was associated with gall bladder bile mucus
      concentrations of 7.6 mg/ml in patients and 7.1 mg/ml in controls (ns). Treatment
      with aspirin led to a significant reduction in mucus biosynthesis by the gall
      bladder mucosa. This action is consistent with a role for aspirin in the
      prevention of gall stones.

PMID- 1398240
TI  - Development of biliary sludge in patients on intensive care unit: results of a
      prospective ultrasonographic study.
AB  - Biliary sludge may be a precursor of gall stones in man. The aim of this study
      was to determine the incidence of biliary sludge in a prospective study of 36
      patients admitted to the intensive care unit for longer than two days. The
      presence of biliary sludge was determined by ultrasonography. Biliary sludge
      developed in 17 patients (47%), after a mean of 5.5 days in the intensive care
      unit. Patients who developed biliary sludge spent longer in the intensive care
      unit (14.2 d (1.3)), compared with patients who did not (8.3 d (1.4)); (p =
      0.003). Ten of the patients with biliary sludge had a recognised risk factor:
      total parenteral nutrition (five), abdominal surgery (two), or both (three). All
      neurosurgical patients (four) who required total parenteral nutrition developed
      biliary sludge. Seven patients with biliary sludge had no previously recognised
      risk factor, five of whom had severe head trauma or neurosurgery. In conclusion,
      biliary sludge develops frequently and rapidly in patients admitted to an
      intensive care unit. Neurosurgical procedures are associated with biliary sludge
      formation. (Sludge is commonly associated with the development of cholestatic
      liver biochemistry.)

PMID- 1398241
TI  - Endotoxaemia and serum tumour necrosis factor as prognostic markers in severe
      acute pancreatitis.
AB  - Endotoxaemia and circulating tumour necrosis factor are important prognostic
      factors in severe sepsis and are implicated in the pathogenesis of septic shock.
      Because clinical and pathological features in acute pancreatitis are similar to
      septic shock this study sought to determine whether endotoxin and tumour necrosis
      factor were prognostic factors in 38 patients with prognostically severe acute
      pancreatitis. Endotoxaemia, present in 19/37 (51%) patients on day 1, was more
      common in nonsurvivors than survivors (10/11, 91% v 9/26, 35%, p = 0.003). Day 1
      serum endotoxin concentrations were higher in patients with a severe outcome
      (median (interquartile range) 314 (173-563) pg/ml v 0 (0-185) pg/ml, p<0.01) and
      in non-survivors (266 (173-586) pg/ml v 0 (0-165) pg/ml, p<0.01). Serum tumour
      necrosis factor was detectable in 47 of 109 samples (43%) from 38 patients
      (median 35 pg/ml, range 5-943 pg/ml). Day 1 serum tumour necrosis factor
      correlated with a worse prognostic score and a severe outcome in all patients (n
      = 38, r = 0.36, p = 0.027; r = 0.33, p<0.05) and with mortality in patients with
      gall stones (n = 23, r = 0.50, p = 0.02). Our data suggest that endotoxin and
      tumour necrosis factor could be prognostic factors in severe acute pancreatitis.

PMID- 1398243
TI  - Rectal motor activity.

PMID- 1398244
TI  - Rectal motor activity.

PMID- 1398245
TI  - Increased intestinal permeability in ankylosing spondylitis.

PMID- 1398242
TI  - Acid-base transport systems in gastrointestinal epithelia.

PMID- 1398246
TI  - Crohn's disease after ileocolic resection.

PMID- 1398247
TI  - Osteomalacia after gastrectomy.

PMID- 1398248
TI  - Papillary cystic neoplasm of the pancreas.

PMID- 1398249
TI  - [Prostaglandins and prostacyclin].

PMID- 1398250
TI  - [Current developments in the use of antibiotics in gynecology and obstetrics].

PMID- 1398251
TI  - [Progesterone antagonists--pharmacology and perspectives of use].

PMID- 1398252
TI  - [Current developments in hormonal contraception].

PMID- 1398254
TI  - [Current status of medicamentous modification of the lower urinary tract].

PMID- 1398253
TI  - [Pharmacology and possibilities for use of gonadotropin releasing hormone
      analogs].

PMID- 1398255
TI  - [Pharmacologic developments for the therapeutic use of biological response
      modifiers].

PMID- 1398257
TI  - [Comments on the contribution by W. Kunzel, The ante-partum CTG (II)].

PMID- 1398256
TI  - [Tumor seeding after laparoscopic cyst puncture].

PMID- 1398258
TI  - [Are gestational hormones for decreasing the membrane potential of the uterine
      muscle cell and saving on the need for betamimetics suitable?].

PMID- 1398259
TI  - [Importance of MR-mammography. Satellite symposium following the 73rd German
      Radiology Congress. Wiesbaden, 17 May 1992].

PMID- 1398260
TI  - Veralipride for hot flushes during gonadotropin-releasing hormone agonist
      treatment.
AB  - Hot flushes are the commonest symptom induced by gonadotropin-releasing hormone
      agonists (GnRHa). We performed an open observational trial to evaluate the
      efficacy of veralipride, an antidopaminergic drug, in reducing hot flushes in 25
      premenopausal women treated with a GnRHa for endometriosis (8 subjects) or
      menorrhagia (17 subjects). The patients received goserelin depot for 6 months and
      veralipride was added for the third month. Hot flushes, severe in all women at 2
      months, improved in both frequency and intensity in 92% of the subjects during
      veralipride administration. The benefit obtained persisted until the end of the
      GnRHa treatment.

PMID- 1398262
TI  - Lymphocyte subset and NK activity in cervical intra-epithelial neoplasia.
AB  - We have studied the systemic T-lymphocyte subset and, in particular, the natural
      killer (NK) activity in 23 patients with cervical intra-epithelial neoplasia
      (CIN), and 11 controls (a history of normal cervical PAP smears and colposcopy
      patterns). The lymphocyte phenotypes were studied using a panel of monoclonal
      antibodies, and NK activity was evaluated as the percentage lysis of K 562 target
      cells. In patients with CIN we found a significant decrease in NK activity (p =
      0.002) which was directly correlated with the grade of CIN, with no alterations
      in the absolute number of NK cells.

PMID- 1398261
TI  - Effect of testosterone on the development of bladder tumors and calculi in female
      rats.
AB  - In order to study the effect of testosterone on bladder calculi and tumor
      formation in female rats, Wistar rats were administered testosterone for 12, 18
      or 24 weeks. Testosterone was found to increase the incidence of both bladder
      calculi and tumors in intact, but not in oophorectomized rats. It is suggested
      that testosterone in combination with estrogen may contribute to hyperplasia
      formation, in turn leading to an increased incidence of bladder calculi and
      tumors.

PMID- 1398263
TI  - Prenatal cytogenetic diagnosis of 1,400 consecutive amniocenteses.
AB  - We report on the incidence of chromosomal abnormalities in 1,400 amniocenteses.
      Thirty-one cases (2.21%) were found to have various types of chromosomal
      abnormality. The majority of abnormal cases (54.84%) were trisomies. All
      individuals with trisomic fetuses chose to terminate the pregnancy with the
      exception of one who gave birth to a Down's syndrome child. However, fetuses with
      apparently balanced translocations were phenotypically normal at birth.

PMID- 1398264
TI  - Successful delivery of twins in a woman with a unicornuate uterus.
AB  - The presence of a unicornuate uterus is a rare congenital condition which
      represents only 1-2% of uterovaginal anomalies. Previous reports have
      demonstrated an increase in the number of cases of primary infertility, pregnancy
      loss and preterm labor associated with the unicornuate uterus. Herein, we present
      a case in which a patient conceived following a thawed frozen embryo transfer.
      She had been given the option of selective reduction, because of the high risk
      associated with this pregnancy, but refused and her pregnancy successfully
      continued to 35 weeks and delivery of twins.

PMID- 1398265
TI  - A lactating adenoma of the breast.
AB  - A lactating adenoma of the breast was first examined at the 24th week of
      gestation, and had doubled in size by the 37th week. After delivery,
      administration of bromocriptine (5 mg/day) reduced its size, and it was
      surgically removed on the 10th day. Histologically, the glandular epithelial
      cells of the adenoma showed the physiological changes normally seen during
      lactation, and retained much of their lactating activity (especially protein
      secretion). The myoepithelial cells contained an increased number of lysosomes
      and also some autophagosomes, implying that the tumor had partly undergone
      involution similarly to the normal breast tissue.

PMID- 1398266
TI  - Tumor markers in gynecologic cancer.
AB  - The development of biochemical tumor markers has increased the use of antibody
      dependent tumor marker assays in gynecologic oncology. Several monoclonal
      antibodies directed against novel epitopes on tumor-associated antigens have
      allowed the development of sensitive assays for serum markers. Assays for human
      chorionic gonadotrophin and TA-4 have been improved. CA 125 has provided a useful
      first-generation markers. Ovarian cystoadenocarcinoma-associated antigen and
      lipid-associated sialic acid have been developed for ovarian cancer, transforming
      growth factor for squamous cancer, and placenta protein 4 for endometrial and
      cervical cancer. The most widely applied procedures to identify these markers are
      immunofluorescent microscopy and immunocytochemical staining. Multiple markers
      and modalities may be required to increase the sensitivity of tumor detection. CA
      15-3 and GCDFP-15 markers have been useful in detecting breast cancer. The
      application of radionuclide imaging will provide a new field for the diagnosis of
      gynecologic malignancies.

PMID- 1398267
TI  - Vulvar oedema among pregnant Mozambican women.
AB  - During a 3-year period, a total of 22 pregnant women with vulvar oedema were
      observed in a high-risk antenatal clinic (ANC) in Maputo. They were compared with
      22 unselected normal ANC attenders, matched for age, parity, gestational length
      and area of living. Reported and observed genital ulcers were more prevalent in
      the oedema group than in the referent group. Reported and observed vaginal
      discharge was also significantly more common in the oedema group. Syphilis
      screening by VDRL was positive in 61.9% of oedema cases while positivity reached
      5.0% in referents (p < 0.005). Cases found seropositive on screening were
      confirmed using Wassermann reaction (WR) in a reference laboratory, in which WR
      positive cases underwent FTA-ABS analysis and IgM assay with solid-phase
      haemadsorption. IgM-positive individuals were significantly more prevalent among
      WR-positive oedema cases than among WR-positive referents (p < 0.05). It is
      concluded that among antenatal attenders in Maputo presenting with vulvar oedema,
      a significant proportion is associated with recent syphilis. Vulvar oedema should
      be considered as an important marker for seropositive syphilis during pregnancy.

PMID- 1398268
TI  - Puerperal measurement of the symphysis-fundus distance.
AB  - Three groups of puerperal women were compared. The first group comprised 51 women
      with clinically evident endometritis-myometritis. This group was compared to 51
      referents (group 2), matched for age, parity and days after delivery. Group 3
      comprised 69 randomly selected, healthy puerperal women coming for postnatal
      check-up of their newborns. Groups 1 and 2 were compared regarding symphysis
      fundus (SF) distance. It was found that puerperal women with clinical signs of
      endometritis-myometritis and healthy, matched referents (groups 1 and 2) did not
      differ in uterine size as measured by the SF distance. The uterine involution can
      be followed by simple anthropometry by assessment of the SF distance over the
      puerperal period. It is concluded that the allegedly swollen and enlarged uterus
      in puerpera with endometritis-myometritis post partum does not differ in fundal
      height from the uterus of healthy, normal puerpera.

PMID- 1398269
TI  - Prepregnancy low body mass index is not a predictor of labor complications.
AB  - The course of delivery and fetal outcome in 149 women with forecoming normal
      pregnancy and a prepregnancy body mass index (BMI) less than 20.0 were compared
      to a similar group of women with BMI between 20.0 and 24.9 after matching for age
      and parity. None of the women was undernourished. Suspected intrauterine asphyxia
      was significantly more common in primipara with BMI below 18.0 than in their
      controls (6/12 vs. 1/12), and there was a trend towards fewer babies weighing at
      least 4,000 g in the women with low BMI. No other significant differences related
      to BMI were found. It is concluded, that constitutional low weight for height is
      not a predictor of complications during delivery, and no special observation of
      this group is recommended.

PMID- 1398270
TI  - Reference values for resistance index and pulsatility index of uteroplacental
      Doppler flow velocity waveforms based on 612 uneventful pregnancies.
AB  - Using a 4-MHz continuous-wave Doppler device, standard rates were established for
      resistance index (RI) and pulsatility index (PI) of uterine and arcuate arteries
      of 612 patients with uneventful pregnancies and deliveries. From 18 to 41 weeks
      of gestation, neither RI nor PI of uterine or arcuate arteries proved to vary
      with gestational age, maternal heart rate, or maternal age. By contrast, a
      significant effect of placental location on the measurement results was found in
      both uterine and arcuate arteries. The differences between measurements on the
      placental or opposite site are more distinct in arcuate than in uterine arteries.
      Taking the 90th percentile as a localization gauge, cutoff levels of 0.52 (RI)
      and 0.98 (PI) were found in uterine arteries. In arcuate arteries, cutoff levels
      of 0.45 (RI) and 0.82 (PI) were found on the placental site or with a placenta
      without lateralization. On the nonplacental site of a lateralized placenta, the
      cutoff levels were 0.51 (RI) and 0.92 (PI).

PMID- 1398271
TI  - Very high collagen increase in placentae of smoking mothers.
AB  - In 55 placentae, collected at term from clinically normal pregnancies,
      hydroxyproline was assayed. Thirty were from mothers who smoke and 25 from
      nonsmokers. In placentae of smokers, hydroxyproline concentration was 42.77 +/-
      8.77 micrograms/mg of tissue and in these of nonsmokers 22.52 +/- 7.46
      micrograms/mg. Such high a difference discloses a large increment in placental
      collagen production in smokers, which may account for some of the noxious effects
      of tobacco on pregnancy.

PMID- 1398273
TI  - Psychological reactions and sexual life after hysterectomy with and without
      oophorectomy.
AB  - A total of 678 women were interviewed about psychological reactions and sexual
      adjustment after abdominal hysterectomy with and without simultaneous
      oophorectomy. The response rate was high and complete questionnaires were
      returned by 86% of the women. A more positive attitude towards the operation was
      found in the group of women where the ovaries had been preserved. Women who had
      undergone oophorectomy experienced a deteriorated sexual life compared to women
      with preserved ovaries. This was observed regardless of age and in different
      parameters such as 'coital frequency' and 'experience of intercourse'. The
      negative effects of sexual life as a result of hysterectomy with simultaneous
      oophorectomy are important to bear in mind and should be discussed with the woman
      prior to surgery.

PMID- 1398272
TI  - Labor characteristics of uncomplicated prolonged pregnancies after induction with
      intracervical prostaglandin E2 gel versus intravenous oxytocin.
AB  - Labor characteristics after intracervical application of 0.5 mg prostaglandin
      (PG) E2 gel (n = 83) versus intravenous administration of oxytocin (n = 82) for
      labor induction were investigated in uncomplicated prolonged pregnancies with
      unripe cervix. The induction to delivery time as well as the total oxytocin dose
      were significantly reduced in the PGE2 group (p < 0.001). Cesarean sections,
      instrumental deliveries and fetal distress had the same frequency, but the
      failures of trial were significantly higher in the oxytocin group than in the
      PGE2 group (20.7 vs. 6%, p < 0.01). Twenty-four percent of women needed a second
      PGE2 dose, and almost half of the women in the PGE2 group experienced
      'spontaneous' labor. More neonates in the oxytocin group had 5-min Apgar scores <
      7 (p < 0.05). Intracervical PGE2 gel application is superior to intravenous
      oxytocin in terms of shortening the induction-delivery interval and increasing
      the frequency of successful vaginal delivery. In addition, it is safe for mother
      and fetus.

PMID- 1398274
TI  - The soluble transferrin receptor: biological aspects and clinical usefulness as
      quantitative measure of erythropoiesis.
AB  - Iron transport in plasma is carried out by transferrin, which donates iron to
      cells through interaction with a specific membrane receptor. In this review, we
      summarize the current knowledge on the structure, intracellular cycle,
      distribution, and regulation of the tissue transferrin receptor. A soluble form
      of the transferrin receptor has been identified in animal and human serum. We
      review the molecular form and origin of the soluble receptor, its dosage in
      normal serum and its relationship with erythropoiesis, iron status, and cancer.
      Lastly, we discuss the clinical usefulness of the soluble transferrin receptor
      for the quantitative determination of marrow erythropoietic activity.

PMID- 1398275
TI  - Functional depletion of T cells by vincristine and methylprednisolone as an in
      vitro model for the prevention of graft versus host disease.
AB  - BACKGROUND AND METHODS. The outcome of mismatched bone marrow transplantation is
      still severely hampered by graft versus host disease (GVHD) and graft rejection.
      Procedures for the recognition and selective elimination of T cells are still
      unsatisfactory due to the increased incidence of graft failure and late
      rejection. Lymphocyte proliferation and generation of cytotoxic T cells (CTL) in
      response to allogeneic cells are considered good in vitro correlates of GVHD and
      have been used in the present study to asses the capacity of two drugs
      (vincristine, VCR, and methylprednisolone, MP) to affect the T cells involved in
      these reactions. RESULTS AND CONCLUSION. Treatment in vitro with VCR and MP has
      been shown to inhibit the functional capacity of peripheral blood lymphocytes to
      proliferate (mean reduction 95.8%) and to generate CTL in response to
      haploidentical stimulator cells. Responsiveness to antigens and mitogens was
      affected to a minor extent (mean reduction 40% and 65.5%, respectively), and the
      method allowed recovery of hemopoietic precursors. The results suggest that
      treatment of donor bone marrow with VCR and MP is worth studying as a new
      approach to the prevention of GVHD in haploidentical bone marrow transplantation.

PMID- 1398276
TI  - M-BCR breakpoint location does not predict survival in Philadelphia chromosome
      positive chronic myeloid leukemia.
AB  - BACKGROUND: Some reports in the recent literature have shown that the site of
      molecular rearrangement within the M-BCR area may have a prognostic value in Ph1
      + CML patients. A number of studies have, however, failed to demonstrate this
      finding. Here we report the molecular rearrangements of 107 patients and their
      clinical follow-up. METHODS: Localization of the breakpoints was determined
      according to conventional criteria, after digestion with 2 to 4 restriction
      endonucleases and hybridization with 1 or 2 molecular probes. RESULTS: Sixty two
      patients were rearranged in the 5' area and 45 in the 3' area: there was no
      difference between the survival curves of the two groups, at least not after 3
      years of follow-up. CONCLUSIONS: The site of the breakpoint within the M-BCR has
      no prognostic significance in our series.

PMID- 1398278
TI  - Proliferation and maturation effects of in-vivo granulocyte-macrophage colony
      stimulating factor in acute non-lymphocytic leukaemia.
AB  - BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) can affect
      the treatment of acute non-lymphocytic leukaemia (ANLL) by supporting normal
      haemopoiesis and by enhancing the proliferation and the maturation of leukaemic
      cells. METHODS: A human recombinant E. Coli synthesized GM-CSF was administered
      to 7 patients with ANLL at a dose of 5 or 10 micrograms/kg/day for 7 days, prior
      to antileukaemic treatment. Peripheral blood neutrophil and blast cell count was
      monitored daily. Changes in marrow blast cell morphologic features, mitotic
      index, and the reactivity to a panel of monoclonal antibodies were assessed after
      3 and 7 days of treatment. RESULTS: Peripheral blood neutrophil and blast cell
      count increased in 6/7 cases. The mitotic index of marrow cells increased in 6/7
      cases. A significant maturation occurred along the granulocytic line (2 cases)
      and the monocytic line (1 case). Mild to moderate eosinophilia developed in 3/7
      cases. Early stem cell markers (CD 34 and HLA-DR) were not lost, or actually
      increased. Myelomonocytic markers (CD 33, CD 13, and CD 14) rose and fell.
      Expression of the multidrug resistance-associated 170 kd glycoprotein remained
      stable. CONCLUSIONS: These data showed that in vivo GM-CSF more consistently
      enhanced the proliferation than the maturation of leukaemic cells.

PMID- 1398277
TI  - Time-dependent sensitivity of rat CFU-GM to total body irradiation.
AB  - BACKGROUND: It has been shown that the light-darkness cycle affects the
      proliferative activity of the hemopoietic system, possibly acting on the
      distribution of the cells in the cell-cycle phases at different hours of the day.
      This could determine time-dependent modifications in ionizing radiation damage to
      hemopoietic progenitors. METHODS: In this study the influence of the irradiation
      time on the radiosensitivity of rat CFU-GM was assessed by in vitro clonogenic
      assay. Rats were exposed to 3 Gy gamma rays at four time points (00:00, 06:00,
      12:00, 18:00 hours). Bone marrow CFU-GM cultures were performed at various
      intervals ranging between 12 hours and 45 days after irradiation and compared
      with unirradiated controls. RESULTS: A marked decrease of femoral CFU-GM was
      observed in the five days following total body irradiation, regardless of the
      irradiation time point. From this interval on all the irradiated groups showed an
      increasing proliferation of CFU, which was particularly evident in the group
      irradiated during the day light period. At the latest intervals (45 days) the
      post-acute damage to hematopoietic progenitors lacked any evidence of time
      dependence. CONCLUSIONS: With the experimental model used, time scheduling does
      not seem to affect markedly either the acute depletion of CFU-GM in the 5 days
      following total body irradiation or the late consequence to the CFU-GM
      compartment.

PMID- 1398279
TI  - Retrospective analysis of platelet serology investigations performed in 1990 by
      twenty laboratories belonging to the "Cooperative Group for the Study of Platelet
      Immunology".
AB  - BACKGROUND: Retrospective co-operative analysis of platelet serology
      investigations was performed during 1990 by twenty laboratories from eighteen
      institutions. METHODS: Data regarding the serological investigations, the methods
      used and the clinical diagnosis of the patients investigated during 1990 were
      collected and analyzed. RESULTS: A total of 2591 patients was investigated,
      including 505 potentially alloimmunized subjects and 2086 subjects with
      autoimmune disease-related conditions. Alloantibodies were detected in 46% of the
      patients, while autoantibodies were detectable in 30% of the autoimmune
      conditions. The antibodies were mostly of the IgG class; however, IgM were
      detected in 19% of alloimmunized patients and in 28% of those with detectable
      autoantibodies. Each laboratory used one or more methods. In all nine methods
      were used. CONCLUSIONS: Collection of the multi-center retrospective results gave
      an approximate picture of the diagnostic potential of the Group, which is ready
      for the next phase of the cooperative activities that will consist of serological
      workshops for technical standardization and antibody characterization.

PMID- 1398280
TI  - Effect of anagrelide on platelet count and function in patients with
      thrombocytosis and myeloproliferative disorders.
AB  - BACKGROUND: Anagrelide is a quinazolin compound developed initially as an
      inhibitor of platelet aggregation. Since "in vivo" studies demonstrated that it
      was responsible for thrombocytopenia in humans, anagrelide has been used recently
      in a small number of patients with thrombocytosis and myeloproliferative
      disorders. Platelet count was well controlled in the large majority of patients,
      and only minimal side effects were observed. PATIENTS: Eight patients (5 with
      essential thrombocythemia, 2 with chronic granulocytic leukemia, and 1 with
      idiopathic myelofibrosis) received anagrelide (induction dose 4 mg/die; mean
      maintenance dose 2 mg/die; mean observation time 26 weeks). Complete blood counts
      were determined 4 times during the first month, and subsequently every month. "In
      vivo" and "ex vivo" platelet function was studied before anagrelide and after 4
      and 10 days of therapy. RESULTS: Platelet count was reduced and maintained below
      500 x 10(9)/L in 5 of 8 patients. Headache, palpitation/tachycardia,
      gastrointestinal symptoms and a decrease in hemoglobin were the side effects.
      Anagrelide did not modify the leukocyte count or "in vivo"/"ex vivo" platelet
      function. CONCLUSIONS: Anagrelide may control thrombocytosis in patients with
      myeloproliferative disorders, even when traditional drugs have failed. When
      required, anti-aggregating drugs may be associated with anagrelide, since it has
      no effect on platelet function.

PMID- 1398282
TI  - High-dose methotrexate administration and acute liver damage in children treated
      for acute lymphoblastic leukemia. A prospective study.
AB  - BACKGROUND: Methotrexate-induced hepatotoxicity following chronic low-dose
      administration has been extensively reported. Current protocols now include high
      dose methotrexate (HDMTX), but there are few studies providing data on its acute
      hepatotoxicity in childhood leukemia. METHODS: To evaluate the prevalence of
      HDMTX-induced acute hepatotoxicity, sixty-eight consecutive children with ALL
      were prospectively studied from diagnosis to the end of HDMTX courses with
      biochemical and clinical evaluation performed at regular intervals. RESULTS:
      Prevalence of HDMTX-induced acute hepatotoxicity was 1.47% (1/68 patients). ALT
      values did not change in 22% (15/68) and decreased in 76.4% (52/68) after HDMTX
      infusion. Mean ALT levels calculated in all the patients decreased significantly
      during HDMTX administration when compared to the values reached during induction
      (p less than 0.0001). Direct hyperbilirubinemia was present only in the child
      with HDMTX-related hepatotoxicity. CONCLUSIONS: The use of HDMTX in the treatment
      of childhood ALL is not associated with major evidence of direct acute
      hepatotoxic effects, while it may modify the pattern of preexisting liver
      diseases.

PMID- 1398281
TI  - Prophylaxis of venous thrombosis after gynaecological surgery: a controlled pilot
      study of defibrotide.
AB  - BACKGROUND: Defibrotide (Def), a new antithrombotic drug, has been proposed as a
      prophylactic agent in postoperative DVT. Most of the studies to date, however,
      have either not been controlled or have used unverifiable systems for
      asymptomatic DVT diagnosis. This randomized pilot study compared Def versus
      standard low-dose calcium heparin (CH) prophylaxis after gynaecological surgery,
      using objective criteria for DVT diagnosis. METHODS: Forty-one pts received 400
      mg Def intramuscularly twice a day starting the day before surgery; 40 pts
      received 5000 IU CH s.c. twice daily beginning 2h before surgery. The two groups
      were well matched for all relevant risk factors. DVT was diagnosed by means of
      the 125I fibrinogen uptake test (FUT) and venography. Blood coagulation and
      fibrinolysis tests were also carried out perioperatively. RESULTS: Isotopic DVT
      (FUT-positive for two consecutive days) was recorded in 6 (14.6%) of the Def and
      5 (12.5%) of the CH groups. In cases where FUT was positive for at least three
      consecutive days (4 in Def and 1 in CH), venography confirmed DVT in 3 cases (all
      in the Def group). No side-effects were recorded in either group and the amounts
      of transfused blood were not different. No significant differences in blood
      coagulation or fibrinolysis tests were recorded, except for higher fibrinogen
      levels on the 8th post-operative day in the Def group. CONCLUSIONS: These results
      do not indicate any trend suggesting that Def, as a prophylactic agent in
      gynaecological surgery, offers any clinical or practical advantages over standard
      low-dose heparin prophylaxis.

PMID- 1398283
TI  - Post-transfusional human retrovirus infection in 41 Italian beta-thalassemic
      patients.
AB  - BACKGROUND: Previous studies have demonstrated that HTLV-I is present in Italy
      both in endemic form in Southern Apulia and in epidemic form among the population
      of intravenous drug addicts. In the present paper we intend to evaluate the risk
      for transfusional HTLV-I transmission in our country, as well as the already
      known risk for HIV1. METHODS: A population of 41 polytransfused Italian beta
      thalassemic patients was examined by serological methods and PCR (polymerase
      chain reaction) for human retrovirus infection. Genomic DNA from PBMCs was
      analyzed by PCR with primer pairs specific for the HTLV-I gag, pol and env
      regions, and the HTLV-II env region. RESULTS: Two patients were found to be
      weakly seroreactive to p19 and p24 HTLV-I/HTLV-II proteins by Western blot. The
      analysis of genomic DNA from PBMCs by PCR revealed sequence homology to HTLV-I
      only in these two patients. On the contrary, PCR with primer pairs specific for
      HTLV-II showed no beta-thalassemic patient was infected by this retrovirus.
      Surprisingly, Western blot analysis for detecting anti-HIV1 antibodies in these
      polytransfused subjects showed a seropositivity in two patients (not the same
      found to be infected with HTLV-I) in spite of a screening for HIV1 antibodies in
      the blood bank. CONCLUSIONS: These findings suggest that in Italy polytransfused
      people should still be considered at risk for HIV1 as well as HTLV-I infection,
      even if the incidence cannot be evaluated from such a small sample. The authors
      stress the importance of a through medical history of potential blood donors to
      eliminate possibly infected subjects.

PMID- 1398284
TI  - Successful use of high-dose cyclophosphamide in a child with severe autoimmune
      hemolytic anemia.
AB  - We report the case of a five-month-old boy with a life-threatening autoimmune
      hemolytic anemia that was unresponsive to conventional therapy with steroids,
      high-dose immunoglobulin, azathioprine and splenectomy. Despite these therapies,
      the patient's condition worsened, requiring 2-3 blood transfusions/day, since the
      hemoglobin level was constantly below 4 g/dl. We eventually increased
      immunosuppression by giving high-dose cyclophosphamide and the child showed a
      striking, sudden improvement, followed by complete recovery. No major long-term
      complications were observed.

PMID- 1398285
TI  - Long-term treatment of refractory HIV-related immune thrombocytopenia in a
      patient with haemophilia A.
AB  - Haemophilia A patient developed symptomatic immune thrombocytopenia 5 years after
      HIV seroconversion without any progression of the viral disease. He displayed
      major bleeding with less than 30 x 10(9) platelets/l. No increase in platelet
      count was obtained using steroids, azidothymidine and alpha-interferon, while the
      patient was responsive only to high-dose intravenous immunoglobulins (IVGG). The
      patient remained responsive to IVGG for 1 year, and the repeated infusions of
      immunoglobulins were effective in safely maintaining the platelet count, with
      peak counts above 100 x 10(9)/l. On the contrary, after a single course of six
      plasma exchanges the patient became symptomatic and completely refractory to IVGG
      during the next month. In conclusion, IVGG could be effectively used in a long
      term regimen in haemophiliacs with refractory HIV-ITP to avoid the risk of
      haemorrhages and to delay splenectomy.

PMID- 1398286
TI  - Delta + 27 homozygosis in a Sicilian family.
AB  - During a screening program to identify at risk couples for beta-thalassemia first
      trimester prenatal diagnosis, we were able to detect, by polymerase chain
      reaction (PCR) and direct genomic sequencing of the PCR product, a homozygosis
      for the G-T substitution at the first nucleotide of codon 27 of the delta-globin
      gene in a pregnant Sicilian woman. The possibility of showing an interaction
      between delta and beta thalassemia is relevant for a thalassemia prevention
      program because it may hide a beta-thal carrier state.

PMID- 1398287
TI  - Prognostic relevance of ploidy and proliferative activity evaluation by flow
      cytometry in poor prognosis non-Hodgkin's lymphomas.
AB  - The DNA content and S-phase fraction (SPF) of pathological paraffin-embedded
      lymph node tissue from 47 patients with poor prognosis non-Hodgkin's lymphoma
      (NHL) were analyzed by flow cytometry (FCM). Fifteen of 42 evaluable cases proved
      to be aneuploid. The DNA aneuploidy was not correlated with age, histology,
      stage, presence of systemic symptoms, clinical response or overall survival (OS)
      of patients. Mean SPF evaluated in 35 cases was 22.9%. After 78 months of follow
      up, nine patients with diploid low SPF tumors had a significantly longer disease
      free survival (DSF) with respect to the group of patients (33 cases) with
      aneuploid or diploid high SPF tumors (100% vs 59%; log rank test, p = 0.04).

PMID- 1398288
TI  - Age as a prognostic factor in primary non Hodgkin lymphoma of the stomach.
AB  - We present 20 cases of primary non-Hodgkin lymphoma of the stomach. Histological
      classification, staging, age of patients and therapeutical approach were
      evaluated. Median overall survival was 30 months, and 5-year survival was 44%. In
      our small series, the age of the patients plays an important role: median overall
      survival is 18 months in patients greater than 60 y.o. (compared to 90 months in
      patients less than 60 y.o.) and 5-year survival 12.5% (compared to 62%).

PMID- 1398289
TI  - Colloidal gold immunostaining for the detection of platelet reactive allo- and
      autoantibodies. Use on fresh and frozen cells.
AB  - BACKGROUND: Fresh washed platelets are commonly used as target cells for the
      detection of platelet reactive antibodies. The use of stored platelets would
      allow a faster execution of the tests and a rapid selection of phenotyped cells.
      METHODS: Glass-adherent platelet monolayers were freeze stored. The antigen
      antibody reaction between platelet antigens and platelet reactive allo- or
      autoantibodies was revealed by a modified antiglobulin test, using colloidal gold
      labeled anti-human IgG. Immunogold staining (IGS) was compared with the platelet
      suspension immunofluorescence test (PSIFT) and with the solid-phase red cell
      adherence assay (SPRCA). The reactivity of fresh and freeze-stored platelets was
      compared. RESULTS: IGS proved to be slightly less sensitive (10%) than PSIFT and
      SPRCA: The results obtained with fresh and freeze-stored cells were scored
      identically. CONCLUSIONS: The immunogold staining assay on freeze-stored
      platelets seems to be a convenient technical approach for platelet serology.

PMID- 1398290
TI  - Ascorbic acid for the treatment of chronic refractory idiopathic thrombocytopenic
      purpura (ITP).
AB  - We describe our experience with ascorbic acid in the treatment of chronic
      refractory ITP. Nine patients, 5 males and 4 females aged 27-74 years, 4 of whom
      were previously splenectomized, received the drug at a daily dose of 2 grams.
      After 2-12 months (median 4) of treatment, a partial response was observed in
      only one patient, while no response was registered in the other eight. Our data,
      analyzed together with those of the literature, allow us to conclude that
      ascorbic acid may not be considered a drug of interest in the treatment of
      chronic refractory ITP.

PMID- 1398291
TI  - G6PD deficiency and diabetes mellitus in northern Sardinian subjects.

PMID- 1398292
TI  - Hodgkin's disease presenting as hemolytic anemia.

PMID- 1398293
TI  - Danazol therapy in myelodysplastic syndromes.

PMID- 1398295
TI  - Hb-M "Hyde Park": a de novo mutation, identified by mass spectrometry and DNA
      analysis.
AB  - BACKGROUND: Structural hemoglobinopathies usually are inherited as autosomic
      dominant traits; de novo mutations are uncommon. Analytical and preparative
      procedures for the characterization of an abnormal hemoglobin are complex and
      time-consuming. Mass spectrometer analysis allows a rapid identification of the
      amino acid substitution. METHODS AND RESULTS: A cyanotic 7-year-old girl was
      found to have 16% methemoglobin. Laboratory data showed the presence of an
      abnormal hemoglobin, which was isolated by collecting the abnormal peak from DEAE
      and globin chains from CM52. The amino acid substitution was rapidly identified
      by FAB mass spectroscopic analysis, leading to the recognition of HbM Hyde Park.
      These data were confirmed by molecular analysis (Southern blot and DNA
      sequencing). Neither the parents nor a sister showed any abnormality; non
      paternity was excluded by blood group serology and HLA typing. CONCLUSIONS: This
      is a case of HbM Hyde-Park arising as a de novo mutation. FAB mass spectroscopic
      analysis is a rapid and useful analytical method for identifying aminoacid
      substitution.

PMID- 1398294
TI  - More on paraproteinemia and hairy cell leukemia.

PMID- 1398296
TI  - A new mutation in the beta-globin gene (IVS II-850 G-C) found in a Yugoslavian
      beta-thalassemia heterozygote.
AB  - BACKGROUND: The recent development of laboratory techniques that can rapidly
      characterize the molecular defects of beta-thalassemia has resulted in the
      discovery of more than 100 different point mutations in the beta-globin gene.
      These mutations are population specific. About 20 of them account for over 90% of
      beta-thal genes in the world. The other mutations are usually found in single
      families. In this paper we describe a case with a novel mutation at position IVS
      II-850 (G-C) as a cause of beta-thalassemia. METHODS: Direct sequencing of PCR
      amplified DNA was used for the detection of the mutation. ASO probes were
      synthesized for dot-blot hybridization. Expression of the mutated allele was
      evaluated through Northern blot and RNA-PCR analyses. RESULTS: This mutation was
      found in four members of a family, who exhibited severe microcytosis and
      hypochromic anemia, with an average alpha/beta ratio of 2.0. The sequencing of
      PCR amplified DNA showed a G-C mutation at position IVS II-850 of the beta-globin
      gene. Dot blot analyses confirmed the presence of this substitution in all four
      carriers. Northern blot and RNA-PCR analyses did not reveal any abnormally
      spliced mRNA species. DISCUSSION: The G-C substitution at position IVS II-850 is
      the third mutation in the invariant AG dinucleotide of the acceptor splice site
      of the second intron of the beta-globin gene. It abolishes normal splicing, which
      leads to abnormally processed mRNA. It is a relatively rare mutation since it was
      not detected among the uncharacterized beta-thal chromosomes from Yugoslavia.

PMID- 1398297
TI  - Loss of surface HLA class I molecules in leukemic myeloblasts is correlated with
      an increased leukocyte concentration at onset.
AB  - BACKGROUND: Reduced expression of HLA class I molecules has been demonstrated for
      many human neoplasias and is correlated with increased malignancy. METHODS: We
      investigated the correlation between HLA expression on blasts and the number of
      peripheral blood leukocytes (WBC) at onset in 34 patients with acute non
      lymphoblastic (ANLL) leukemia. Leukemic blasts at onset were serologically typed
      for HLA-A,B specificities, and the patients were classified in three groups
      according to the number of detectable surface HLA antigens. RESULTS: The amount
      of WBC at onset in patients lacking HLA antigens was significantly higher than in
      patients with no antigenic loss. CONCLUSIONS: A decrease in HLA class I molecules
      on the cell surface is correlated with a greater expansion of the leukemic clone.

PMID- 1398298
TI  - Evidence for the co-existence of immunocomplexes and platelet specific antibodies
      in HIV infection-related thrombocytopenia in narcotic drug addicts. Experimental
      results and immunopathogenetic discussion.
AB  - BACKGROUND: The development of symptomatic or asymptomatic thrombocytopenia is
      not uncommon in HIV seropositive drug addicts. METHODS: Platelet binding
      immunoglobulins, as immune complexes or as platelet specific antibodies, were
      studied in eleven patients. Whole sera anche serum factions obtained by PEG
      sedimentation and gel filtration were investigated using methods able to
      characterize the IgG and IgM immunoglobulin classes. Immune complexes-containing
      fractions were used in competition assays with some monoclonal antibodies with
      receptor specificities. RESULTS: Immune complexes able to bind both autologous
      and allogenic platelets were detected in all patients, while platelet specific
      IgG or IgM autoantibodies were detected in most, but not in all, patients. The
      results obtained with the various individual tests were sometimes discrepant,
      owing to the low avidity binding of platelet-reacting immunoglobulins. Anti-low
      affinity FcRII monoclonal antibody moderately reduced the platelet binding of IgG
      containing immune-complex fractions. CONCLUSIONS: In thrombocytopenic, HIV
      seropositive drug addicts immunecomplexes and platelet specific antibodies
      usually coexist and possibly have different pathogenetic potential in the
      development of thrombocytopenia.

PMID- 1398299
TI  - Cytotoxic effects of dacarbazine in patients with acute myelogenous leukemia: a
      pilot study.
AB  - BACKGROUND AND METHODS: Preclinical studies performed in our laboratory showed
      that mouse leukemias become highly immunogenic following in vivo treatment with
      Decarbazine. This observation led to a successful immunochemotherapy protocol in
      mice using Dacarbazine plus cytoreductive chemotherapy. Therefore an in vivo and
      in vitro pilot study was conducted in patients (pts) with resistant or relapsed
      acute myelogenous leukemia (AML). The DNA-repair enzyme O6-alkylguanine-DNA-alkyl
      transferase (OGAT) and the in vitro chemosensitivity to Temozolomide, a
      Dacarbazine derivative, were evaluated in leukemic blasts. RESULTS: Nine pts
      received Dacarbazine (0.4-0.8 g/sqm/day) on days 0, 1 and 2. On day 7, noticeable
      blast reduction occurred in 4 pts: pt 1 was in partial remission on day 21, pt 6
      still showed bone marrow leukemia, pt 8 died of sepsis on day 8, pt 9 is still in
      aplasia on day 25. Low OGAT levels and consistent sensitivity to Temozolomide in
      vitro were found in the blasts of pts responsive to Dacarbazine. Subsequently,
      pts 1-7 underwent Ara-C (1g/sqm/day) plus Mitoxantrone (6mg/sqm/day) treatment
      for 6 days. Four pts entered complete remission after 27-45 days of aplasia.
      Failures were due to hypoplastic death, absolute drug resistance, or hypoplasia
      followed by blast cell regrowth. CONCLUSIONS: These data point out that
      Dacarbazine can induce a marked reduction of blast cells as well as severe
      myelotoxicity in leukemic patients.

PMID- 1398300
TI  - B-cell acute lymphoblastic leukemia (B-ALL): a report of 17 pediatric cases.
AB  - BACKGROUND AND METHODS: B-cell acute lymphoblastic leukemia (B-ALL) presents FAB
      L3 morphology and surface Ig, CD19, CD20, CD24. This pattern may show some
      morphological and immunological heterogeneity. Seventeen pediatric cases of B-ALL
      at onset, treated in twelve AIEOP Centers (Italian Association for Pediatric
      Hematology and Oncology), are presented. RESULTS AND CONCLUSIONS: Clinical and
      hematological features were characterized by low WBC counts at presentation, high
      M/F ratio, older age and association with extramedullary involvement. The overall
      survival curve at 78 months is 40%. All patients showed blasts positive for
      surface Ig (sIg), DR, CD19, and CD24. Ten/17 cases presented the classical
      features of B-ALL: FAB L3 morphology, sIg+ restricted to light chains, CD20+,
      cytoplasm mu (c mu)-, CD10-, TdT-. The remainder showed some differences in this
      pattern, such as non-L3 morphology (3 cases), absence of CD20 (3 cases), CD10+ (4
      cases), TdT+ (3 cases), c mu+ (1 case), lack of surface light chains (1 case).
      This rare ALL subset seems to be characterized by a high phenotype heterogeneity,
      indicating various degrees of differentiation.

PMID- 1398301
TI  - Primary gastrointestinal lymphoma: a clinicopathological study of 58 cases.
AB  - BACKGROUND: Primary non Hodgkin's lymphoma (NHL) of the gastrointestinal tract
      (GI) is the most frequent extranodal lymphoma accounting for approximately 40% of
      all extranodal primary NHL. The role of surgery and other treatment modalities in
      the management of these patients is still controversial. PATIENTS AND METHODS: We
      reviewed the records of 68 patients with primary GI-NHL. Ten patients had
      incomplete records and were excluded from further evaluation. The records of 58
      patients were considered, and all were available for analysis and follow-up.
      RESULTS: The most frequent site of involvement was the stomach (47 patients),
      followed by ileum (7 patients), large bowel (3 patients) and duodenum (1
      patient). Malignant lymphomas of follicular center cell origin represented the
      most prevalent histologic types, accounting for 58% (34 of 58) of all cases.
      Stage, evaluated according to the criteria of Musshoff, was Ie in 15 cases, IIe
      in 16, IIIe in 7, and IV in the remaining 20 cases. The median survival for the
      entire group of 58 patients was 54 months, with 46% of patients surviving at 5
      years. The median survival was 71 months for patients in stage I-II, 60 for
      patients in stage III, and 25 for patients in stage IV (p = 0.016). Moreover, we
      found significantly improved survival in patients undergoing surgical tumor
      resection (p = 0.003). CONCLUSIONS: Even if at the present time the optimal
      management of primary GI-NHL is difficult to assess, our data suggest that it is
      prudent to advise resection followed by adjuvant CT in most patients, whereas CT
      alone should be considered only when surgery cannot be performed.

PMID- 1398302
TI  - Prolymphocytic leukemia: a very satisfactory response to treatment with
      recombinant interferon alpha.
AB  - We report the case of a patient with prolymphocytic leukemia in whom a lengthy
      survival of 5 years was observed after treatment with splenic irradiation and
      chemotherapy. The patient obtained a surprising improvement with a significant
      reduction in the absolute count of the prolymphocytes and considerable reduction
      in splenomegaly after 3 months' therapy with interferon alpha.

PMID- 1398303
TI  - Chronic lymphocytic leukemia coexisting with chronic myelomonocytic leukemia.
AB  - A case with coexisting chronic lymphocytic leukemia (CLL) and chronic
      myelomonocytic leukemia (CMML) is described. A 74-year-old man with a typical B
      CLL also showed sustained peripheral blood and bone marrow monocytosis. Typical
      myelodysplastic changes and monosomy 7 were also found. Cytographic and
      immunophenotypic analysis confirmed the presence of two distinct cell
      populations, i.e., lymphoid and monocytoid. Both malignancies presented an
      extraordinarily benign prognosis. It remains uncertain whether monocytosis was
      either the expression of a distinct myelomonocytic clone or the progeny of a
      B/monocytic bipotential precursor able to feed both leukemic phenotypes.

PMID- 1398304
TI  - An unusually prolonged case of heparin-induced thrombocytopenia and disseminated
      intravascular coagulation.
AB  - An unusually prolonged case of heparin-induced severe thrombocytopenia and
      decompensated disseminated intravascular coagulation (DIC) is described. The
      patient, treated with heparin at a dosage of 25,000 units/day for 3 days and
      12,500 units/day for an additional 4 days because of a clinically suspected deep
      venous thrombosis, developed (4 days after the discontinuation of heparin) a
      clinical and laboratory picture of severe DIC, manifested by subcutaneous
      hematomas and ecchymoses. Platelet count was 24 x 10(9)/l, fibrinogen level 89
      mg/dl and fibrin-degradation products between 3,200 to 6,400 ng/ml. A thorough
      laboratory and instrumental evaluation failed to demonstrate any underlying
      disorder. No heparin-dependent aggregating factor was detected in the serum of
      the patient. The patient recovered spontaneously. Whereas fibrinogen and fibrin
      degradation products reverted to normality within four weeks, platelet count
      normalization was delayed until the sixth week after heparin discontinuation.

PMID- 1398305
TI  - Antithrombin III biological activity and emotional stress in patients with
      coronary artery disease.
AB  - We studied the effect of emotional stress (mental arithmetic for 10 minutes) in
      ten postinfarction patients and in ten age-matched, apparently healthy subjects
      as controls. Blood samples for the determination of epinephrine and AT III levels
      were taken in basal conditions, at the end of mental stress and after 30 minutes
      of recovery. Mental stress induced a significant increase in epinephrine levels
      and a significant decrease in AT III levels in control subjects. Both parameters
      returned to baseline values after 30 minutes of recovery. On the contrary, in
      postinfarction patients AT III levels of recovery were still significantly lower
      than those of baseline, suggesting a reduced ability to restore the original
      concentration of this physiologic inhibitor. Our data can contribute to a better
      understanding of the complex relationships among phychosocial factors, the
      haemostatic system and vascular disease.

PMID- 1398306
TI  - Recombinant erythropoietin for refractory anemia with ring sideroblasts.

PMID- 1398307
TI  - Monoclonal antibody-induced platelet aggregation does not require interaction
      between antibody and platelet Fc receptor.

PMID- 1398308
TI  - Ascorbic acid for the treatment of autoimmune thrombocytopenic purpura.

PMID- 1398309
TI  - CNS toxicity and high-dose busulphan in three patients undergoing bone marrow
      transplantation.

PMID- 1398310
TI  - [Cochlear implantation].
AB  - Since the Israeli cochlear implant program was started in June 1989, 74
      candidates have been evaluated for implantation. The main causes for hearing loss
      were meningitis (16 patients), aminoglycoside toxicity (9), congenital (6), viral
      (e.g. mumps) (6), and middle ear infection. Candidates were rejected mainly due
      to psychosocial factors (40%) and audiological parameters (30%). 16 postlingual
      deaf were implanted. In 7 of them (43.7%) the results were excellent, in 4
      (25.0%) good, in 3 (18.7%) fair; 1 case is currently in a training program and 1
      is a failure. There were 2 major complications: facial nerve palsy which
      necessitated surgical decompression, and insertion of the electrodes into the
      hypotympanic air cells, corrected by reoperation.

PMID- 1398311
TI  - [Psychological aspects of cochlear implantation].
AB  - Psychological aspects of cochlear implantation were studied in 20 adults and
      children. Patients were interviewed before admission and were given tests and
      questionnaires to answer with regard to overall wellbeing, intellectual
      functioning, hopes and beliefs, expectations with regard to the implant and the
      support they were getting (last 2 also for a family member). Those who passed the
      screening were referred for surgery, and those who didn't were referred for
      therapy. 6 months after implantation the patient and the family member were again
      interviewed and answered questionnaires with regard to adjustment to the implant
      and the patient's satisfaction with it. In those who benefitted from the implant
      there were no psychopathological features, there was good cognitive functioning,
      a moderate level of concentration and attention span and a great degree of
      flexibility in personality traits. Crucial to better adjustment was quality of
      family support. Following cochlear implantation there was considerable
      improvement in life style.

PMID- 1398312
TI  - [Psychosocial characteristics of phenylketonuric women: birth defect prevention].
AB  - Women with phenylketonuria (PKU) are at high risk for having offspring with
      mental retardation, microcephaly, heart defects and low birth weight. These
      adverse outcomes can be prevented by a low-phenylalanine diet started before
      conception and continued throughout pregnancy. In view of the frequency of poor
      dietary compliance in women with PKU, a psychosocial model was developed that
      delineates developmental stages with specific behavioral goals for them to
      follow. In the present study 15 women with PKU over the age of 16 were followed
      for 3 years and compared to groups of their healthy acquaintances and of diabetic
      women. Structured interviews and standard questionnaires were used to study
      factors hypothesized as being related to the subjects' adjustment and to
      achievement of their PKU-related behavioral goals. After 1 year most of the PKU
      subjects were not planning a pregnancy, making their main behavioral goal the
      prevention of an unplanned pregnancy. Their knowledge of the risks of maternal
      PKU and family planning was unsatisfactory. PKU subjects had more conservative
      attitudes about sex and contraception than the controls. The psychosocial profile
      of PKU subjects pinpointed their special needs and indicated the kinds of
      specific intervention that might help them adhere to the recommended treatment
      and prevent birth defects in their offspring.

PMID- 1398313
TI  - [Physical training in coronary patients with poor left ventricular function].
AB  - Physical training is beneficial in patients with coronary artery disease, and in
      those after myocardial infarction in whom left ventricular function and ejection
      fraction (LVEF) are relatively well preserved. However, little is known about the
      effect of physical training in coronary patients with impaired left ventricular
      function. 12 patients after myocardial infarction (range 42-60 years) with LVEF
      of 30% or less at rest were evaluated after 11 months of isotonic physical
      training. Mean LVEF increased from 28.0% to 33.0% (p less than 0.002) at rest and
      from 29.4% to 33.2% (p less than 0.002) on effort. Exercise tolerance increased
      228 seconds by the end of the study (p less than 0.001); the double product at
      symptom limit effort increased (p less than 0.001) and the double product at the
      same work load decreased (p less than 0.002). During training there was no
      cardiovascular deterioration and all patients returned to work within a mean of
      3.7 months. The results show that patients with severe left ventricular
      impairment should not necessarily be excluded from cardiac rehabilitation
      programs involving physical training.

PMID- 1398315
TI  - [Complications of laparoscopic cholecystectomy].
AB  - 92% of our first 60 laparoscopic cholecystectomies were successful. Postoperative
      complications included fever in 10 cases (17%), urinary retention in 5 (8%),
      intraabdominal abscess in 2 (3%), biliary leakage in 1 (2%) and unexplained
      abdominal pain in 10 (17%). Although laparoscopic cholecystectomy has obvious
      advantages, it also has major as well as minor complications.

PMID- 1398314
TI  - [Calcific periarthritis in patients with endstage renal disease on chronic
      dialysis].
AB  - 2 patients with end-stage renal disease undergoing dialysis developed calcific
      periarthritis. A 25-year-old man on hemodialysis developed arthritis of 2 right
      metacarpophalangeal joints and a 65-year-old man on chronic ambulatory peritoneal
      dialysis suffered from pain and tenderness in the left buttock. Treatment with
      nonsteroidal antiinflammatory drugs in the first case and periarticular injection
      of methylprednisolone (Depomedrol) in the second were successful.

PMID- 1398316
TI  - [Echinococcus cyst of the breast imitating carcinoma].
AB  - A 3 x 4 cm breast mass in a 38-year-old woman was surgically removed and was
      found to be an echinococcal cyst; thorough investigation failed to reveal any
      other hydatid cysts. Echinococcal cyst should be considered in the differential
      diagnosis of the much more common malignant breast mass.

PMID- 1398317
TI  - [Acute dopamine deficiency and malignant neuroleptic-like syndrome].
AB  - A 60-year-old woman, under treatment for parkinsonism with dopicar, was
      hospitalized in a stuporous catatonic state. After several days, while dopicar
      was being tapered off, she developed a clinical picture similar to malignant
      neuroleptic-like syndrome, including continuous high fever, elevated blood
      pressure and increased perspiration, and the parkinsonian symptoms became more
      severe. Neuroleptic medication was not used, but renewal of dopicar treatment
      relieved this typical syndrome. It is suggested that a relative deficiency of
      dopamine is involved in the pathogenesis of malignant neuroleptic-like syndromes.

PMID- 1398318
TI  - [Bloody nipple discharge in an infant].
AB  - A milky discharge from the nipple and breast hypertrophy are often seen in mature
      infants, but bloody nipple discharge is very rare in infancy and childhood. In
      adults, a bloody discharge may be associated with breast carcinoma, but in
      infants it is a benign, self-limited condition that should be managed
      conservatively. Surgical procedures should be avoided, because injury to the
      breast bud may cause permanent damage. We report a 3-month-old girl who presented
      with a bloody discharge from the left nipple. The discharge diminished gradually
      in the course of time and ceased completely at the age of 9 months.

PMID- 1398319
TI  - [Institutions and homes for the disabled and handicapped: the present and the
      ideal].

PMID- 1398321
TI  - [Anticoagulants after myocardial infarction].

PMID- 1398320
TI  - [Screening tests for cystic fibrosis in the neonate].

PMID- 1398322
TI  - [The role of sympathetic nervous system in heart failure].

PMID- 1398323
TI  - [Infection and human parturition].

PMID- 1398324
TI  - [Viral gastroenteritis in Israel].

PMID- 1398325
TI  - [Iodine-131 meta-iodobenzylguanidine for the diagnosis and treatment of
      pheochromocytoma and tumors of neural crest origin].

PMID- 1398327
TI  - [Lactase deficiency--symptomatology and diagnosis].

PMID- 1398326
TI  - [Occupational scleroderma due to organic solvent exposure].
AB  - Progressive systemic sclerosis (PSS; scleroderma) is a multisystem disease
      characterized by inflammation, fibrosis and degeneration of the integument, with
      similar changes and vascular lesions in the heart, lungs, kidneys,
      gastrointestinal tract and synovia. Its etiology is not clear. Several
      occupational exposures have been implicated as potential causes of PSS and
      scleroderma-like diseases. Among them are vinyl chloride monomer, silica dust,
      epoxy resin, and benzene and other solvents, aromatic and aliphatic, specifically
      chlorinated (trichloroethylene, perchloroethylene and trichloromethane). We
      present a patient whose illness was diagnosed as occupationally induced PSS.
      During 13 years of work renovating carburetors he was heavily exposed to
      trichloromethane. To the best of our knowledge this is the first reported case of
      PSS due to exposure to organic solvents in Israel; very few cases have been
      reported from abroad.

PMID- 1398328
TI  - [Treatment of the sleep apnea syndrome].

PMID- 1398329
TI  - [Cochlear implantation].

PMID- 1398330
TI  - [Hypertonicity in the neonate and infant].

PMID- 1398331
TI  - [Peripheral serotonin receptors: respiratory and circulatory modulation].
AB  - The wide distribution of serotonin (5-HT) receptors and 5-HT-mediated effects
      suggest that 5-HT has important physiological and/or pathophysiological roles in
      the peripheral nervous system. Recent studies about the localization and release
      of 5-HT in the peripheral nervous system suggest that 5-HT likely plays a
      functional role in regulating discharge of autonomic neurons and modulating
      sensory afferent neurons. The electrophysiological approach has the merit of
      measuring a direct effect of 5-HT on its receptor. In this review, much of our
      described work focuses on effects mediated via 5-HT3-receptors on respiration and
      circulation using electrophysiological techniques, and we consider whether these
      actions of 5-HT have physiological and/or pathophysiological significance.

PMID- 1398332
TI  - [Molecular pharmacology of endothelin in the cardiovascular system].
AB  - Endothelin-1 (ET-1), ET-2 and ET-3 are 21-amino acid peptides that act to
      stimulate contraction of many smooth muscle tissues including blood vessels,
      uterus, bladder, and intestine. In the case of each ET, the 21-amino acid
      bioactive form is produced from each precursor (referred to as big ET) via
      specific conversion between Trp-Val (ET-1, ET-2) or Trp-Ile (ET-3). Northern blot
      analysis of the mRNA for the ET isoform as well as determination of the peptide
      itself revealed that they are independently expressed in various tissues,
      indicating that each isoform may play separate physiological or
      pathophysiological roles. However, the vascular endothelial cells appear to
      produce only ET-1. Since ET-1 was first discovered, the majority of
      investigations so far reported have been concerned with this particular peptide.
      This review will focus on ET-1 with respect to the regulation of its biosynthesis
      in endothelial cells and its precise pharmacological actions on the
      cardiovascular system including the cerebral, coronary and renal circulations.
      Sub-classification of ET receptors was made from molecular biological,
      biochemical as well as pharmacological points of view. The signal transduction
      for mechanisms of action was also explained in detail.

PMID- 1398333
TI  - [The recent development and the present status of K+ channel opener].
AB  - The development of vasodilator drugs that open the K+ channels in blood vessels
      has been of great academic and practical interest. The discoveries of the ATP
      sensitive K+ channel and the glibenclamide-sensitive K+ channel have promoted
      these interests. In relation to this channel, the cardioprotective effectiveness
      of a K+ channel opener (Aprikalim) in doses that did not change haemodynamics or
      collateral blood flow were demonstrated in infarct dog heart. The effects were
      antagonized by glibenclamide. Thus, ATP-sensitive K+ channels seem to play an
      important role in this effect. Clinical evaluations of the K+ channel openers are
      reviewed. The hypotensive effects of the drugs are well-recognized. At present,
      however, the clinical usefulness of K+ channel openers has not been accepted
      widely, because of their side-effects including reflex tachycardia, edema,
      flushing and headache. An approach to reduce these side-effects is critical if
      these K+ channel openers are to be used as good hypotensive drugs. The K+ channel
      opener nicorandil has been evaluated as a highly effective antianginal drug. It
      seems likely that the clinical benefits of nicorandil result from both its K+
      channel opening properties and its ability to stimulate smooth muscle guanylate
      cyclase. Clinical data on the pure-selective K+ channel opener cromakalim
      (lemakalim) as an antianginal drug is limited. However, on the basis of the
      vasodilator profile of this drug, it is expected to be useful for this purpose.
      The application of K+ channel openers to treat other disorders such as bladder
      instability is limited because of its hypotensive action.

PMID- 1398334
TI  - [Molecular pharmacology of intracellular Ca2+ messenger system in cardiovascular
      function: development and application of selective inhibitors].
AB  - The importance of Ca2+ for the transmission of information inside living cells is
      well-recognized. The mobilized Ca2+ binds to the intracellular Ca2+ binding
      proteins to transmit the Ca2+ signal. Calmodulin is the most important Ca2+
      binding protein to exert pleiotropic effects on various cellular functions by
      activating multiple enzymes. To determine the physiological significance of the
      Ca2+ messenger system, specific inhibitors are quite essential. We have been
      originally developing novel and selective inhibitors, and analyzing the several
      processes involved in information flow in the Ca(2+)-dependent regulatory system
      of cell functions. The aim of this review is to introduce our research strategy
      for the production of selective inhibitors towards calmodulin-dependent enzymes
      and to discuss recent progress in the understanding of the multiple calmodulin
      dependent pathways that mediate the action of exogenous physiological stimuli. We
      summarize much of the pharmacological evidence that has led to our current
      knowledge of calmodulin-regulated cell functions, with emphasis on aspects that
      may be relevant to drug design. These H-series inhibitors are one of the most
      powerful tools as molecular probes for pharmacological approaches, and will shed
      light on the physiological significance and molecular mechanisms of the
      calmodulin-dependent pathways in various cell functions.

PMID- 1398335
TI  - [Central effect of Ca2+ channel blockers: multiple sites of action].
AB  - To develop a new concept of central acting drugs, the modulation of brain Ca2+
      flux must be considered as one of the important factors. This is because
      excessive Ca2+ influx to neuronal cells damages or kills these cells, and also
      because abnormal intracellular Ca2+ concentrations induce several types of mental
      disorders. Recently, both pre-clinical and clinical studies indicated that some
      Ca2+ channel blockers (Ca antagonists) will be useful for the treatment of grand
      mal, manic depressive insanity, panic disorder and anxiety. Furthermore, it has
      been estimated by animal studies and clinical pharmacology that ischemia-induced
      neuronal death can be prevented by the treatment with a Ca antagonist. However,
      the latter data, especially, has been mainly explained by pharmacological effects
      on the cerebrovascular system, not because of possible direct central actions. To
      invoke the notion of direct central action, it must be assumed that Ca
      antagonists might pass the blood-brain barrier (BBB). This potentiality that some
      Ca antagonists (i.e., flunarizine, nicardipine, nimodipine, etc.) can pass the
      BBB has been initially explored. If substantiated, such direct central effects of
      Ca antagonists may explain both the psychotropic effects and neuronal protection
      by these agents. To investigate the actual therapeutic effects of Ca2+
      antagonists on psychotropic disorders and neuronal death, a suitable animal model
      and reasonable methods and criteria must be established. Then, both preclinical
      and clinical studies can be expected to relate to atypical central acting drugs
      modulating the brain Ca2+ channels, and also to the development of new
      pharmacological properties of Ca2+ antagonists.

PMID- 1398336
TI  - [Novel types of cardiotonic drugs].
AB  - Since the use of cardiac glycosides for heart failure therapy is limited by their
      narrow margin of safety, numerous efforts have been made to find and develop
      novel cardiotonic agents that are superior to the cardiotonic glycosides.
      Positive inotropic drugs acting on beta-adrenoceptors and inhibitors of cAMP
      phosphodiesterase have been extensively studied for the treatment of patients
      with heart failure. The main mechanism of these agents is elevation of cAMP
      tissue levels. Furthermore, Ca sensitizers such as sulmazol, pimobendan, MCI-154,
      END 53998 and DPI 201-106 are of interest, since such a mechanism of action may
      be beneficial for the failing heart. Recently, cardiotonic substances with a
      novel mechanism of action such as gingerol and xestoquinone have been isolated
      from natural sources. Natural products, purealin, goniodomin and okadaic acid,
      have proven to be valuable pharmacological tools for studies on cardiac muscle
      contraction.

PMID- 1398337
TI  - [Thrombus models and mechanisms of action of anti-platelet drugs].
AB  - Thrombus formation is initiated by platelet aggregation, followed by activation
      of the blood coagulation system, so that anti-thrombotic drugs can be classified
      into anti-platelet drugs, anti-coagulation drugs and fibrinolytic drugs. A
      variety of thrombus models in animals have been reported. Microthrombus formation
      in arterioles in the microcirculation is useful for analyzing the nature of the
      thrombus and the process of thrombus formation. Platelet aggregation can be
      divided into two types: (a) reversible aggregation (Rev-Aggr), in which platelets
      do not release their granular contents and are able to return to the resting
      discoid shape and (b) irreversible aggregation (Irrev-Aggr), in which platelets
      release their granular contents. Irrev-Aggr is inhibited by aspirin and not by
      PGI2 at the maximum aggregation, whereas Rev-Aggr is not inhibited by aspirin and
      inhibited by PGI2 even at the maximum aggregation. Thrombi corresponding to
      either type of platelet aggregation can be produced in arterioles in the
      microcirculation. An ADP-induced thrombus, which is composed of Rev-Aggr of
      platelets and disaggregated automatically, is not inhibited by indomethacin, but
      inhibited by PGI2. In contrast, a stable thrombus, which is composed of Irrev
      Aggr of platelets and keeps its initial shape for a longer period, is sensitive
      to indomethacin, but resistant to PGI2. Thus, anti-thrombotic drugs should be
      developed and used for targeting the individual processes of thrombus formation.

PMID- 1398338
TI  - [Studies on anti-nephritic effects of plant components (5). Effects of
      pherodendrin on original and crescentic-type anti-GBM nephritis in rats].
AB  - Effects of pherodendrin (OB-5) on anti-GBM nephritis were investigated. OB-5 (50
      mg/kg/day, i.p.) prevented the urinary protein excretion in original and
      crescentic-type anti-GBM nephritis in rats. In addition, OB-5 also inhibited the
      elevation of serum creatinine, urea nitrogen and cholesterol contents in both
      models of nephritis. Histopathological observations indicated that OB-5 prevented
      the hypercellularity, crescent formation, adhesion and fibrinoid necrosis in the
      glomeruli of nephritic rats. OB-5 and cyclosporine A, a positive control drug,
      prevented the increase in the number of OX-1, CD8 and ED-1 positive cells in the
      glomeruli. These results indicated that OB-5 may be effective in human
      glomerulonephritis, and anti-nephritic mechanisms of OB-5 may be due to its
      inhibition of the activation of macrophages or cytotoxic T cells.

PMID- 1398340
TI  - [Effects of KW-6055, a novel benzylpyridine derivative, on central cholinergic
      systems].
AB  - We examined the effect of KW-6055 [alpha-(p-butyrylamino-o-nitrobenzyl)
      pyridine], which has anti-amnesic activity, on the central cholinergic systems of
      rat frontal cortex using in vivo brain microdialysis. 1) KW-6055 (40, 160 mg/kg,
      p.o.) increased the extracellular level of ACh in normal rats (257 +/- 23, 202 +/
      24%). The stimulating effect of KW-6055 on ACh release was abolished by
      tetrodotoxin treatment, supporting that the released ACh was due to neuronal
      firing. Reserpine pretreatment decreased the effect of KW-6055, indicating that
      KW-6055 acted on cholinergic neurons through catecholaminergic neurons. 2) In
      basal forebrain-lesioned rats, KW-6055 (40 mg/kg, p.o.) significantly increased
      the extracellular level of ACh (251 +/- 22%) for more than 2 hr, which was longer
      than in normal rats. In conclusion, these results suggest that the stimulating
      activity on ACh release may be involved in the mechanism of the anti-amnesic
      effects of KW-6055.

PMID- 1398339
TI  - [Effects of the new cardiotonic agent loprinone hydrochloride (E-1020) on left
      ventricular diameter in normal and experimental heart failure dogs and its action
      potential characteristics in isolated guinea pig cardiac muscles and sinus
      nodes].
AB  - In anesthetized dogs, loprinone hydrochloride (LP, 10 approximately 100
      micrograms/kg, i.v.) dose-relatedly increased cardiac contractility (LV dP/dt
      max), enhanced cardiac index and decreased systemic vascular resistance with
      relatively small reduction in mean aortic pressure (MAP) and a mild increase in
      heart rate (HR). LP also decreased left ventricular internal diameter (ID),
      increased fractional shortening (LVFS) and caused a leftward shift and an
      increase in the slope of the LV end-systolic pressure-ID relation. In the heart
      failure models induced by propranolol, LP rapidly reversed the cardiac depression
      and the enlargement in cardiac size. The extent of changes in MAP and HR by LP
      was smaller than those observed with several other cardiotonic agents. In guinea
      pig cardiac muscles, LP (10(-6)-10(-4) M) produced a concentration-related
      increase in contractile force and the maximum rate of rise of Ca(2+)-action
      potential. In the sinus nodes, LP induced a concentration-related decrease in
      action potential duration and increase in the slope of slow diastolic
      depolarization, resulting in an increase in beating rate. These influences of LP
      on sinus nodes were smaller than those of milrinone. These results indicate that
      LP increases LVFS, reduces cardiac size and improves the heart failure due to its
      cardiotonic and vasodilating properties. Moreover, electrophysiological studies
      suggest that at least a part of the lower chronotropic effects of LP may be due
      to the mildness of its direct stimulating effects on sinus nodes.

PMID- 1398341
TI  - [Study on the kinetics of bradykinin level in the wound produced by thermal
      injury in the ear burn model in mice].
AB  - The kinetics of bradykinin derived from localized thermal injury on vascular
      permeability were investigated in mice with experimental ear burn. The leakage of
      plasma into the ear tissue by accelerated vascular-permeability reached the
      maximum at 3 hr and decreased gradually until 6 hr after the thermal injury. The
      contents of bradykinin increased by the thermal injury and the increment
      continued up to 24 hr. Although the bradykinin contents in the burned ear
      decreased by using a protease inhibitor, the hyperpermeability of injured ear
      vessels was unchanged by protease inhibitors. These results suggest that
      bradykinin is concerned with the pain reaction rather than vascular-permeability.

PMID- 1398342
TI  - Chromosomal rearrangements and speciation of sportive lemurs (Lepilemur species).
AB  - Theoretical configurations of meiotic chromosomes of potential hybrids between
      the different Lepilemur species were examined, and the classification of this
      genus was reviewed in the light of this information. Among the chromosomal
      rearrangements that occurred during the chromosomal evolution of the sportive
      lemurs, only those which would generate a pronounced reproductive barrier were
      considered in relation to the geographic distribution of this genus. The analysis
      showed that the pattern of geographic distribution is compatible with the
      inferred chronological occurrence of these chromosomal rearrangements in the
      phylogenetic tree of the genus Lepilemur.

PMID- 1398343
TI  - The size of the neocortex in relation to ecology and social structure in monkeys
      and apes.
AB  - In an attempt to reveal factors associated with neocortical development in
      monkeys and apes (anthropoids), relationships between the relative size of the
      neocortex and differences in ecology and social structure were examined for 24
      genera of 11 subfamilies. Relative sizes of the neocortex (RSNs) in a given group
      were assessed as the difference between actual neocortical volume and the volume
      expected from an allometric relationship between neocortical volume and the
      volume of the rest of the brain. We found that RSNs are related to diet and
      social structure: frugivorous anthropoids had higher values of RSNs than
      folivorous anthropoids, and polygynous anthropoids had significantly higher
      values of RSNs than monogynous anthropoids. Furthermore, RSNs were positively
      correlated with the size of the troop. These results suggest that development of
      the neocortex is associated with both diet and social structure in anthropoids.

PMID- 1398344
TI  - Functional significance of female Japanese macaque copulatory calls.

PMID- 1398345
TI  - Agonistic tactics in competition for grooming and feeding among Japanese
      macaques.

PMID- 1398346
TI  - Competitive utilization of Bagassa fruits by sympatric howler and spider monkeys.

PMID- 1398347
TI  - Genotoxicity and cell transformation studies with sorbates in Syrian hamster
      embryo fibroblasts.
AB  - Sorbic acid, sodium sorbate and potassium sorbate were tested for their genotoxic
      potential in the Syrian hamster embryo (SHE) fibroblast micronucleus assay and
      the SHE cell transformation test in vitro. Sorbic acid and potassium sorbate
      showed no activity in either test system. When freshly prepared sodium sorbate
      solutions were used, no genotoxic or cell-transforming activity was detected.
      However, sodium sorbate as stored solution, which previously had been heated and
      sonicated to facilitate solubilization, yielded a positive response in both test
      systems. It is concluded that oxidation products of sodium sorbate that possess
      genotoxic and cell-transforming properties are formed under conditions of
      heating, sonication and storage.

PMID- 1398348
TI  - Lack of carcinogenicity of tragacanth gum in B6C3F1 mice.
AB  - Tragacanth gum was administered at dietary levels of 0 (control), 1.25 and 5.0%
      to groups of 50 male and 50 female B6C3F1 mice for 96 wk after which all animals
      were maintained on a basal diet without tragacanth gum for a further 10 wk. Mean
      body weights of females in the 5.0% and 1.25% groups were lower than those of the
      controls after 11 and 16 wk, respectively. However, there were no treatment
      related clinical signs or adverse effects on survival rate, urinalysis,
      haematology, blood biochemistry and organ weight. While detailed histopathology
      revealed the development of squamous cell hyperplasias, papillomas and one
      carcinoma in the forestomach, there was no significant treatment-related increase
      in the incidence of any preneoplastic or neoplastic lesion. Thus, under the
      experimental conditions used, tragacanth gum was not carcinogenic in B6C3F1 mice
      of either sex.

PMID- 1398349
TI  - Inhibitory effect of carbohydrates on the formation of mutagens in fried beef
      patties.
AB  - Beef patties were prepared by mixing minced meat with water and either glucose
      (1, 2 or 4%), lactose (1, 2 or 4%) or powdered milk (2, 4 or 8%) before frying.
      In another experiment, minced meat was mixed with starch from golden bread crumbs
      (3%) or potatoes (4%), with and without glucose (1, 2 or 4%). The patties (100 g)
      were fried for 3 min at 150 or 180 degrees C in a double-sided fryer. The
      mutagenic activity in the crust was determined using the Ames test. With the
      addition of glucose or lactose (1-4%), the mutagenic activity was inhibited by 34
      76%. A similar inhibition of the mutagenic activity was obtained with powdered
      milk. However, starch from golden bread crumbs or potatoes caused only a slight
      (not significant) decrease in mutagenic activity whereas adding both starch and
      glucose to the beef patties inhibited mutagenic activity by up to 54%.

PMID- 1398350
TI  - Absence of genotoxicity of potato alkaloids alpha-chaconine, alpha-solanine and
      solanidine in the Ames Salmonella and adult and foetal erythrocyte micronucleus
      assays.
AB  - To assess whether reported toxicities of potato-derived glycoalkaloids could be
      the result of interactions with cellular DNA, the genotoxic effects of alpha
      solanine, alpha-chaconine and solanidine were studied, using the Ames test
      (Salmonella strains TA98 and TA100), the mouse peripheral blood micronucleus test
      and the mouse transplacental micronucleus test. The Ames test for mutagenicity
      with alpha-solanine was weakly positive in TA100 with S-9 activation (29
      revertants per millimole per plate). However, pooled data from duplicate tests
      gave a negative effect. Pooled data from two experiments with alpha-chaconine
      gave a weak positive response in TA98 without microsomes (17 revertants per
      millimole per plate). The micronucleus tests for clastogenicity using male mouse
      and foetal blood were negative. The absence of mutagenicity and clastogenicity
      suggests lack of damage to intracellular DNA for potato alkaloid toxicity.

PMID- 1398351
TI  - Effects of dietary lipids on whole-body retention and organ distribution of
      organic and inorganic mercury in mice.
AB  - The effect has been investigated of dietary lipids on the whole-body retention
      and organ distribution of organic and inorganic mercury in mice. A single oral
      dose of methylmercury chloride or mercuric chloride labelled with 203Hg was given
      to female NMRI mice fed semi-synthetic diets containing varying amounts (5, 10,
      20 or 50%) of energy derived from lipid (coconut oil, soya oil, or cod liver
      oil). The whole-body retention and relative organ distribution of mercury
      depended on diet composition. Thus, a significant reduction of the whole-body
      retention of mercury was seen in mice fed a diet containing 50% cod liver oil
      compared with mice fed a diet containing 50% coconut oil. After oral
      administration of mercuric chloride the relative deposition of mercury in the
      kidneys increased while that in the liver decreased with increasing
      concentrations of soya oil or coconut oil in the diet. The whole-body retention
      of mercury after treatment with methylmercury chloride was significantly
      decreased in mice fed cod liver oil compared with mice fed coconut oil; there was
      no difference between mice fed cod liver oil and those fed soya oil. The relative
      disposition of mercury was significantly higher in all organs of mice fed a diet
      containing 20% energy from cod liver oil compared with mice fed a diet containing
      20% energy from soya oil. The present study demonstrates that diet composition is
      of major importance to the toxicokinetics of methylmercury and mercuric mercury.

PMID- 1398352
TI  - Effect of dietary cholestyramine on the elimination pattern of ochratoxin A in
      rats.
AB  - Three experiments with rats established the effects of dietary cholestyramine on
      the disposition of ochratoxin A (OA) and its hydrolysed metabolite, alpha
      ochratoxin (O alpha). In the first experiment OA (1 mg/kg) was incorporated into
      a diet that contained 0, 0.5, 1.0 and 2.0% cholestyramine. Cholestyramine
      markedly reduced blood concentrations of OA (1.6 to 0.75 micrograms/ml, P less
      than 0.0001) for all concentrations of the resin. The second experiment
      demonstrated that 2% cholestyramine added to the diet of rats markedly reduced
      cumulative urinary OA excretion (26 to 6 micrograms, P less than 0.01) and
      increased cumulative faecal OA excretion (8 to 38 micrograms, P less than 0.001).
      The third experiment established the efficacy of cholestyramine (2%) when added
      to diets containing two concentrations (0 and 6%) of a saturated fat (tallow).
      The bioavailability of OA as determined by area under the blood concentration
      curve over 216 hr was 424 micrograms/ml/hr for the control rats and 186
      micrograms/ml/hr for the cholestyramine-treated rats (P less than 0.0001).
      Cholestyramine treatment increased the recovery of OA plus O alpha in the faeces
      plus urine over a 5-day period from 65.5 to 96.2% (P less than 0.0001).
      Cholestyramine also greatly increased the amount of OA plus O alpha and
      particularly of OA excretion in the faeces (105 to 160 micrograms, P less than
      0.0001 for OA plus O alpha and 82 to 150 micrograms, P less than 0.0001 for OA)
      and resulted in a corresponding decrease in the excretion of these compounds in
      the urine. The concentration of fat in the diet had a much less dramatic effect
      than cholestyramine, was mainly detected in the urine and was affected by an
      interaction with cholestyramine (P less than 0.0001). Cholestyramine greatly
      reduced the concentration of OA plus O alpha (37 v. 8 micrograms) when the
      content of dietary fat was low but to a much lesser degree when it was high (19
      v. 12 micrograms). These results suggest that the concentration of fat in the
      diet may affect the pattern of OA excretion in the urine. Cholestyramine added to
      the diet greatly increases the amount of OA eliminated in the faeces and reduces
      the amount in the urine, and as a result it decreases the amount present in the
      systemic circulation.

PMID- 1398353
TI  - Effect of subchronic bis(tri-n-butyltin)oxide (TBTO) oral administration on
      haematological parameters in monkeys: a preliminary report.
AB  - A preliminary study was conducted on adult male crab-eating monkeys (Macaca
      fascicularis) orally exposed to bis(tri-n-butyltin)oxide (TBTO) at doses of 0 and
      160 micrograms/kg/day, 6 days/wk, for 22 wk. No treatment-related signs of
      toxicity or changes in body weight gain were detected during the course of the
      study. The haematological analyses performed every 2 wk indicated a decrease in
      total leucocyte count in the treated animals with significant values in wk 8, 10
      and 22 of treatment. No differences from controls were noted in clinical
      chemistry and total tin concentration in blood. These preliminary data on the
      toxicity of TBTO in the primate model are intended to be an initial contribution
      towards a better evaluation of the potential toxicological hazard of TBTO to
      humans.

PMID- 1398354
TI  - Effect of prototypic polychlorinated biphenyls on hepatic and renal vitamin
      contents and on drug-metabolizing enzymes in rats fed diets containing low or
      high levels of retinyl palmitate.
AB  - Two groups of weanling male Sprague-Dawley rats fed a diet supplemented with
      either 0.6 or 6 retinol equivalents/g diet were each separated into three further
      groups receiving 300 mumol 2,2',4,4',5,5'-hexachlorobiphenyl/kg body weight, 300
      mumol 3,3',4,4'-tetrachlorobiphenyl kg/body weight or vehicle only (corn oil).
      Only the coplanar (3,4)2Cl congener caused a slight reduction in food intake,
      thymic atrophy and led to a significant decrease in the liver vitamin A storage.
      The vitamin A lost by the liver was approximately the same in both dietary
      groups; however an increased renal accumulation of vitamin A was observed in the
      high vitamin A group. Serum retinol was reduced by (3,4)2Cl treatment but
      remained unchanged by (2,4,5)2Cl exposure. Total amounts of ascorbic acid and its
      oxidation products were increased in the liver and in the kidney by both
      xenobiotics while niacin and thiamine concentrations were lowered by (3,4)2Cl
      only. Microsomes from vitamin A-deficient rats exhibited a marked decrease in the
      anisotropy parameter. After (2,4,5)2Cl exposure, an increase in membrane fluidity
      was observed linked to a decrease in cholesterol/phospholipid (C/P) ratio.
      Treatment with (3,4)2Cl caused a significant decrease in the index of
      fluorescence polarization only in the low vitamin A group even if the C/P ratio
      was enhanced in both dietary groups. This study shows that the polychlorinated
      biphenyl with the 3-methylcholanthrene-type pattern of induction of cytochrome P
      450 has more profound effects on B group vitamins and particularly vitamin A
      homeostasis than does the phenobarbital-type inducer. Moreover, this situation,
      which has been found to be similar to that in vitamin A deficiency, is not
      ameliorated by a high dietary vitamin A intake.

PMID- 1398355
TI  - Is dietary ergotamine atherogenic in the rabbit?
AB  - The effect of dietary ergotamine on pre-lesional indicators of atherosclerosis
      was studied in rabbits. The experimental purified diets contained 0.08% (w/w)
      cholesterol and either 0, 40 or 200 mg ergotamine-tartrate/kg. After 6 wk, serum
      total cholesterol concentration and the ratio of serum total cholesterol: high
      density lipoprotein-cholesterol were significantly increased by ergotamine in a
      dose-dependent manner. Dietary ergotamine raised the total level of
      glycosaminoglycans and the relative proportion of chondroitin sulphate in the
      abdominal aorta. It is suggested that dietary ergotamine is atherogenic in the
      rabbit.

PMID- 1398356
TI  - Long-term follow-up of the Conaxial (Beck-Steffee) total ankle arthroplasty.
AB  - Between 1975 and 1977, 30 patients with traumatic arthritis or rheumatoid
      arthritis underwent 36 Conaxial (Beck-Steffee) ankle replacements (DePuy, Warsaw,
      IN). Thirty-two were primary replacements and four were revisions of previous
      ankle arthroplasties. Twelve patients had traumatic osteoarthritis and 18
      patients had rheumatoid arthritis. The average age at operation of patients with
      rheumatoid arthritis was 61 years (range 28-67 years) and with osteoarthritis was
      52.9 years (range 32-72 years). The average follow-up was 10.8 years, with a
      range of 10 to 13 years. Early postoperative complications included wound
      dehiscence in 39% of patients (14 patients), deep wound infection in 6%,
      fractures of the medial or lateral malleolus in 22%, and painful talofibular
      impingement in 14%. At 2-year follow-up, 27% of the ankle replacements were
      loose. Sixty percent were loose at 5 years and 90% were loose at the 10-year
      follow-up. Ten patients had implant removal and attempted fusion. Six, or 60%,
      fused in an average of 5 months. Of those patients who achieved ankle fusion,
      four had internal fixation and iliac crest autografting, one had a Charnley
      compression apparatus with allograft bone, and one had internal fixation with
      allograft bone. The constrained Conaxial ankle replacement should no longer be
      implanted because of a 90% loosening rate at 10 years and an overall complication
      rate of 60%.

PMID- 1398357
TI  - Ankle arthrodesis: a long-term study.
AB  - Few studies of ankle arthrodesis have assessed tarsal mobility. This study was
      performed to evaluate radiographically the effect of ankle arthrodesis on tarsal
      motion. Thirty patients (31 ankles) returned for clinical and radiographic
      examination, review of charts, and completion of questionnaire forms. Radiographs
      were evaluated for success of fusion, position of fusion, tarsal motion, hindfoot
      position, and subtalar and midtarsal arthritis. The median follow-up time was 7.0
      years (range 2-20 years). Results showed that fusion was achieved in 22 patients
      (71%). The evaluation score based on the grading system of Mazur et al.
      correlated with success of fusion and patient satisfaction. However, no
      correlation existed between evaluation score and tarsal motion or position of
      fusion in the sagittal or coronal planes. Radiographic evaluation showed no
      significant difference between tarsal motion of the fused side and the unfused
      side. Tarsal mobility was not affected by ankle arthrodesis or by the techniques
      performed to achieve fusion.

PMID- 1398358
TI  - Talonavicular arthrodesis in the rheumatoid foot.
AB  - Arthrodesis of the talonavicular joint with a cylindrical dowel was performed in
      19 feet in 17 rheumatoid patients with arthritic destruction of the talonavicular
      joint, but without fixed hindfoot deformity. Osseous union was achieved in 12
      feet, but all patients experienced pain relief and no foot showed progressive
      valgus deformity of the hindfoot during follow-up. Staple fixation seemed to
      promote osseous union. The procedure, easy to perform and requiring only 6 weeks
      of immobilization, may, in the absence of fixed hindfoot deformity, supersede
      triple arthrodesis in rheumatoid patients with hindfoot arthritis.

PMID- 1398359
TI  - Excision arthroplasty for hallux valgus in the elderly: a comparison between the
      Keller and modified Mayo operations.
AB  - A retrospective clinical and radiological review of 51 patients (mean age 66
      years) was performed to assess the outcome of excision arthroplasty for hallux
      valgus in an elderly population and to compare the results of the Keller, which
      is still used frequently in many centers in the United Kingdom, and modified Mayo
      operations. Although significant correction of the deformity was obtained with
      both procedures, this was incomplete and the mean residual hallux valgus angle
      was greater than 20 degrees. Lateral metatarsalgia was present in over 40% of
      patients. Both procedures provided good pain relief, and considerable narrowing
      of the forefoot was obtained with the modified Mayo operation. Excision
      arthroplasty in the elderly should be reserved for the low demand patient with
      symptomatic degenerative changes in the first MP joint in the absence of lateral
      metatarsalgia.

PMID- 1398360
TI  - Hallux valgus correction with proximal metatarsal osteotomy: two-year follow-up.
AB  - We evaluated the results of 33 feet in 23 patients who underwent a basilar
      crescentic osteotomy with a modified McBride procedure with a minimum 24-month
      follow-up. The average hallux valgus improved from 37.5 degrees to 13.8 degrees
      and the intermetatarsal 1-2 angle from 14.9 degrees to 4.7 degrees. The angle of
      declination of the first metatarsal was found to have dorsiflexed an average of
      6.2 degrees. Unfortunately, osteotomies secured with staples dorsiflexed to a
      greater degree. Bilateral foot surgery produced results similar to those with
      unilateral procedures. Four of our patients developed a hallux varus (range 2-8
      degrees); however, none were dissatisfied at the time of evaluation. Although
      this bunion procedure resulted in more prolonged swelling and pain than a distal
      osteotomy, it should be considered for more complex deformities to avoid the
      failure that a distal metatarsal osteotomy might produce given a high 1-2
      intermetatarsal angle or a high hallux valgus angle.

PMID- 1398361
TI  - Adult acquired flatfoot deformity at the talonavicular joint: reconstruction of
      the spring ligament in an in vitro model.
AB  - The mobile unilateral flatfoot deformity of chronic posterior tibial tendon
      insufficiency has been difficult to correct by soft tissue procedures. The
      procedures can decrease pain, but they do not always correct the longitudinal
      arch or relieve all the symptoms. Using 10 fresh frozen cadaveric specimens and a
      rig for stimulation of weightbearing, the deformity associated with chronic
      posterior tibial tendon insufficiency was produced by multiple ligamentous
      release and documented by AP and lateral radiographs. Reconstruction of the
      spring ligament using a ligament bone autograft from the superficial deltoid
      ligament was then performed and tested under load. The mean correction was within
      2.5 degrees of normal (over or undercorrection) on both the AP and lateral
      radiographs with the specimens under load. Clinical Relevance. In posterior
      tibial tendon insufficiency, it may be possible to address the ligament as well
      as tendon insufficiency to gain a corrected arch. The success of such a procedure
      will depend upon adequate tendon and ligament reconstruction in a fully mobile
      deformity. Questions remain as to the adequacy of this ligament graft, and a
      stronger free ligament graft, as well as correction of any bony malalignment, may
      be required.

PMID- 1398362
TI  - Arthrodesis of the first metatarsophalangeal joint using interfragmentary screw
      and plate.

PMID- 1398364
TI  - The pneumatic ankle tourniquet with ankle block anesthesia for foot surgery.
AB  - The use of a pneumatic ankle tourniquet applied to the supramalleolar ankle
      region is a useful method of obtaining a bloodless field in surgery of the foot.
      The pneumatic ankle tourniquet allows for more accurate and reproducible control
      of circumferential compression than the standard Esmarch bandage, when used in
      conjunction with the regional ankle block. Between March 1987 and October 1990,
      84 foot surgeries were performed using the pneumatic tourniquet and ankle block
      technique on 76 patients by one surgeon. Tourniquet ischemia lasted from 30 to
      105 min. Tourniquet pressure was set to 100 to 150 mm of mercury above systolic
      blood pressure without exceeding 325 mm of mercury. Two patients reported mild
      pain directly beneath the tourniquet after 45 and 70 min, respectively. Neither
      patient required deflation of the tourniquet to complete the procedure. The
      clinical and electrophysiologic evidence showed that no neurologic or vascular
      damage occurs. The use of the pneumatic tourniquet in conjunction with regional
      ankle block anesthesia provides a reasonable alternative to the standard thigh
      tourniquet for surgery of the foot.

PMID- 1398363
TI  - Range of motion of the foot as a function of age.
AB  - Movement of the foot is essential for human locomotion. The purpose of this paper
      was to quantify the range of motion of the foot as a function of age and to
      compare the rage of motion measurements for the foot in a laboratory coordinate
      system and a coordinate system fixed to the tibia. The measurements were taken in
      vivo using a range of motion instrument developed by Allinger (University of
      Calgary, Canada, 1990) from 121 subjects. The results suggest that: (1) the range
      of motion in general is greater for women than for men in the young adult group;
      (2) the range of motion in general is in the same order of magnitude for women
      and men in the oldest age group; and (3) the range of motion is about 8 degrees
      smaller in dorsiflexion and about 8 degrees higher in plantarflexion for women
      than for men in the oldest age group. It is speculated that physical activity and
      common shoe wear are factors influencing the age- and gender-dependent
      differences in range of motion. Furthermore, it has been shown that the range of
      motion values measured in a laboratory coordinate system and in a coordinate
      system fixed in the tibia are different in all directions except inversion. The
      differences in plantarflexion and dorsiflexion and inversion and eversion are
      relatively small. However, they are substantial for adduction and abduction. In
      all cases, the results were bigger for measurements in the laboratory coordinate
      system compared with the tibia coordinate system, because the movement of the
      lower leg was included in the measurements in the laboratory coordinate
      system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398365
TI  - Percutaneous suture of Achilles tendon ruptures.

PMID- 1398366
TI  - Calcaneal spurs in a black African population.
AB  - The radiological incidence of calcaneal spurs in a black African population was
      studied. Our findings show that spur incidence increased with age and was greater
      in females than in males. These results, the first from a large, exclusively
      African population, are similar to those from previous studies of individuals
      from other continents.

PMID- 1398367
TI  - Coalition of the hallux sesamoids: a case report.
AB  - Multiple variations in partition of the hallux sesamoids have been described;
      however, to our knowledge, a coalition of the hallux sesamoids has never been
      presented. A case of coalition of the hallux sesamoids is presented and the
      literature is reviewed with respect to the possible significance of this anomaly.

PMID- 1398368
TI  - The microvasculature of the sesamoid complex: its clinical significance.
AB  - The microvascular anatomy of the sesamoid complex was investigated in 15 cadaver
      specimens using histology and tissue clearing (Spalteholz) techniques. It was
      found that both sesamoids appeared equally well vascularized and the vascular
      supply to each sesamoid originated from two major sources (proximal and plantar)
      and one minor source (distal). Proximally, vessels originating from the first
      plantar metatarsal artery enter the sesamoid at its attachment to the flexor
      hallucis brevis. In addition, vessels enter the plantar surface of the sesamoid
      near the midline and arborize throughout the bone, anastamosing with the proximal
      vessels. The distal vascular supply to the sesamoids originates from its distal
      capsular attachment and appears to contribute minimally to the overall vascular
      scheme. The lateral attachments of the sesamoids to the plantar plate and joint
      capsule were relatively avascular. In two bipartite specimens examined, the major
      blood supply originated from the proximal and distal poles of the sesamoid. No
      vessels were observed entering the plantar surface of these specimens. The
      results of this study suggest that injury to the proximal or plantar aspects of
      the sesamoids could disrupt the vascular supply to these bones. These areas
      should, therefore, be avoided during the surgical approach to the sesamoids.

PMID- 1398369
TI  - Dislocation of the posterior tibial tendon.

PMID- 1398370
TI  - An investigation into pellet dispersion ballistics.
AB  - Existing works on pellet dispersion ballistics are confined to some data-based
      models derived from statistical analysis of observed patterns on targets but the
      underlying process causing the dispersion lacks due attention. The present
      article delves into the relatively unexplored areas of dispersion phenomena, and
      attempts to develop a theoretical model for general application. The radial
      velocity distribution of pellets has been worked out by probing into the physical
      process of dispersion based on transfer of momentum from undispersed shot mass to
      dispersed pellets. The ratio 2u/v0 (u = root mean square (r.m.s.) radial velocity
      and v0 = muzzle velocity of the pellets) is found to be fairly constant for a
      fixed gun-ammunition combination and has been suitably designated as 'Dispersion
      Index' (DI) characterising its dispersion capability. The present model
      adequately accounts for pellet distribution on targets and it appears that
      'Effective Shot Dispersion' (ESD) as introduced by Mattoo and Nabar [ESD =
      [(4/N0)sigma Ri2]1/2, where N(0) is the total number of pellets and Ri is the
      radial distance of the i-th pellet from centre of pattern], gives a faithful
      numerical measure of overall dispersion at a given distance. A relationship
      between ESD and firing distance, incorporating the effects of air resistance and
      gravity has been worked out, which reveals that DI controls the dispersion at a
      given distance. For small distances (less than 20 m) the relation reduces to a
      linear one, as already observed empirically and looks like ESD = E0+DI x firing
      distance, E0 being a parameter dependent on gun and ammunition. The present
      model, unlike earlier ones, is versatile enough to explain the natures of the
      dependence of dispersion on firing distance as well as on gun-ammunition
      parameters, which are essential for a faithful reconstruction of a crime scene.
      The model has been tested with such experimental data as are available and
      reasonable agreement is observed.

PMID- 1398371
TI  - SEM analysis of red blood cells in aged human bloodstains.
AB  - Mammal red blood cells (RBC) in bloodstains have been previously detected by
      light microscopy on stone tools from as early as 100,000 +/- 25,000 years ago. In
      order to evaluate the degree of morphological preservation of erythrocytes in
      bloodstains, an accidental human blood smear on white chert and several
      experimental bloodstains on hard substrates (the same stone-white chert; another
      type of stone-graywacke; a non-stone support-stainless steel), were stored in a
      room, in non-sterile and fluctuating conditions, for lengths of time ranging from
      3 to 18 months. Afterwards, the specimens were coated with gold and examined by a
      Cambridge Stereoscan 120 scanning electron microscope. Results revealed a high
      preservation of RBC integrity, with the maintenance of several discocytary
      shapes, a low tendency to echinocytosis and a frequent appearance of a moon-like
      erythrocytary shape in the thinner areas of the bloodstains.

PMID- 1398372
TI  - Rapists' behaviour: a three aspect model as a basis for analysis and the
      identification of serial crime.
AB  - In this paper it is proposed that the behaviour of an offender during a sexual
      assault can be considered as consisting of three main groupings or 'aspects'.
      These have been termed 'Modus Operandi', 'Sexual and Personal Gratification' and
      'Attitude and Intimacy'. Although an oversimplification, such a model facilitates
      a preliminary description of the offender which can be of direct assistance to an
      investigating officer. Various factors affect the consistency and variability of
      behaviour and the model has formed a basis for the development of a concept as to
      which behaviours might be the more useful for identifying linked offences. This
      more systematic approach to the investigative and intelligence processes is
      reliant on a victim's statement containing very detailed information about the
      offender's actions, together with a record of as much of his speech as can be
      recollected. The material required is described using the model and the text is
      illustrated with case examples. Instances are quoted of the possible inferences
      and their relevance to the investigation of sexual offences.

PMID- 1398373
TI  - Discrepancy between estimated and actual time elapsed after death of a severed
      head.
AB  - A severed head which had been wrapped in seven plastic bags and set in concrete
      in an airtight insulated plastic box was found approximately 22 months after the
      occurrence of death. Ammonium magnesium phosphate had formed and on the basis of
      this and other observed postmortem changes, time elapsed after death was
      estimated to be from 2 weeks to 6 months. The absence of oxygen is thought to
      have contributed significantly to the great discrepancy between estimated and
      actual time elapsed after death.

PMID- 1398374
TI  - Sex allocation of skeletal material by analysis of the proximal tibia.
AB  - In this study we contrasted the confidence with which individuals may be grouped
      and then reallocated on the basis of a set of measurements from the proximal
      tibia. The data were derived from 100 Caucasoid (50 male) and 102 Negro (50 male)
      tibia housed in the R.A. Dart Collection. Multivariate discrimination was
      effected by means of canonical and stepwise discriminant analyses, whilst
      probabalistic models were used to allocate individuals. High levels of correct
      classification (84.62-92%) were matched by high levels of reallocation,
      suggesting that, in contrast to dental or craniobasal measurements, those of the
      proximal tibia may be usefully employed to allocate an individual on the basis of
      sex.

PMID- 1398375
TI  - A fatal case of poisoning with cantharidin.
AB  - A case of fatal poisoning due to voluntary ingestion of cantharides powder for
      aphrodisiac purposes is reported. Clinical history, autopsy and analytical
      findings are described. Blood and urine samples collected during the 30 h of
      survival, as well as the cantharides product, were analyzed by gas chromatography
      mass spectrometry. On the basis of the percentage of the active principle
      measured in the powder, an ingested dose of 26-45 mg of cantharidin could be
      estimated.

PMID- 1398377
TI  - Death by greyhound.
AB  - We present the case of a man who was last seen leaving to feed his greyhound
      dogs. He was found dead lying in a yard just outside the gate to one of the dog
      pens. Holes were present in the fence on both sides of the gate. The holes were
      of sufficient size to allow the passage of the head and neck of a greyhound to
      the shoulders. To open the gate one had to bend down to unfasten a latch 45 cm
      above ground level. Leaning down to unfasten the latch brought one into close
      proximity to the holes on either side of the gate. The scene and clothing
      appeared undisturbed. Autopsy (K.A.L.) revealed the cause of death to be blunt
      throat trauma. The throat trauma was of marked degree and consistent with at
      least a single heavy crushing injury directed from the front and somewhat below.
      In addition there were a series of almost vertical light abrasions on one side of
      the neck. There were minimal injuries to the rest of the body. There were no
      injuries specific for assault. In an attempt to explain the almost vertical
      abrasions on the side of the neck, the scene was re-examined by the pathologist.
      This revealed loose wire strands on the gate post. It is consistent that a fall
      against this area could account for the almost vertical abrasions on one side of
      the neck.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398376
TI  - An exceptional case of lethal disulfiram-alcohol reaction.
AB  - A case of fatal disulfiram-alcohol reaction due to ingestion of ethanol and
      antabuse is presented. Unusual autopsy findings and toxicological results are
      described. This case represents a report of corrosion lesion in the lower
      oesophagus and stomach due to a violent chemical reaction in situ and also the
      highest blood concentration of acetaldehyde (41 mg/l) ever recorded.

PMID- 1398378
TI  - Firearm fatalities.
AB  - One hundred and twenty eight cases of shooting fatalities were investigated
      during an 11-year period. Of these 57% were homicidal shootings with 34% suicidal
      in nature. Only two suicidal fatalities were female. Analysis of the sites of
      entrance wounds confirmed the 'sites of election' in suicidal shootings, whilst
      homicidal wounds showed a much wider distribution. Multiple entrance wounds were
      seen in 42% of homicidal shootings. Injuries to hands were seen in 7 homicidal
      fatalities.

PMID- 1398379
TI  - Identification of the skeletal remains of Josef Mengele by DNA analysis.
AB  - There has been considerable controversy over the identity of the skeletal remains
      exhumed in Brazil in 1985 and believed to be those of Dr Josef Mengele, the
      Auschwitz 'Angel of Death'. Bone DNA analysis was therefore conducted in an
      attempt to provide independent evidence of identity. Trace amounts of highly
      degraded human DNA were successfully extracted from the shaft of the femur.
      Despite the presence of a potent inhibitor of DNA amplification, microsatellite
      alleles could be reproducibly amplified from the femur DNA. Comparison of the
      femur DNA with DNA from Josef Mengele's son and wife revealed a bone genotype
      across 10 different loci fully compatible with paternity of Mengele's son. Less
      than 1 in 1800 Caucasian individuals unrelated to Mengele's son would by chance
      show full paternal inclusion. DNA analysis therefore provides very strong
      independent evidence that the remains exhumed from Brazil are indeed those of
      Josef Mengele.

PMID- 1398380
TI  - Retinal hemorrhages: replicating the clinician's view of the eye.
AB  - The authors describe a technique for the gross examination of postmortem eyes of
      children who are suspected to have been the victims of deliberate trauma. By
      removing the anterior segment (cornea, iris, lens and pars plicata of the ciliary
      body) en bloc by a coronal incision through the pars plana just anterior to the
      ora serrata, the pathologist may view and photograph the fundus exactly as it
      would have been seen clinically. The photographs obtained with this technique
      correlate more closely with antemortem clinical examinations and photographs than
      conventional gross examination procedures and have been introduced as evidence in
      trials concerning the issue of retinal hemorrhages in injured children. The
      anterior segment and optic nerve are also examined to facilitate a comprehensive
      description of ocular findings.

PMID- 1398381
TI  - Sudden unexpected death due to Taxus poisoning. A report of five cases, with
      review of the literature.
AB  - The toxicity of yew (Taxus) has been known since antiquity. However, in the past
      31 years, to our knowledge only six cases of Taxus poisoning have been reported
      in the literature. In the present paper we add five cases. From a forensic point
      of view, intoxication with Taxus has three important aspects: (i) the clinical
      presentation, which among other causes should suggest Taxus intoxication; (ii)
      the fact that the diagnosis may often be easily made by examination of the
      contents of stomach, duodenum and small bowel and (iii) the widespread
      availability in the near future of Taxol, an anti-neoplastic drug which is an
      alkaloid extracted from Taxus. The clinical and autopsy findings are summarized,
      the diagnostic aspects are discussed and the literature concerning Taxus is
      reviewed.

PMID- 1398382
TI  - Suicide by self-stabbing.

PMID- 1398383
TI  - [Iatrogenic origin of pleural effusion. A rare complication of the central venous
      catheter].
AB  - CASE REPORT: A 47-year-old woman with unremarkable plain chest X-rays in whom the
      Seldinger technique was employed to place a central venous line via the jugular
      vein, a catheter-related pleural effusion developed. CONCLUSIONS: This case
      points up the need to exercise care when placing a central venous line, and
      suggests the need to use contrast medium for the radiological follow-up
      examination.

PMID- 1398384
TI  - [Diagnosis of female urinary incontinence. Progress with urodynamic functional
      diagnosis].
AB  - PROBLEM: Owing to its frequency and severe consequences for the women affected,
      urinary incontinence poses a considerable problem. Our knowledge about its
      pathophysiology, as also the diagnostic and therapeutic possibilities, remain
      remarkably limited. TYPES OF INCONTINENCE: The main types of incontinence are
      stress, urge, reflex and overflow incontinence. Other forms are rare. A major
      diagnostic and therapeutic problem is posed by the mixed type, which can account
      for up to 60 percent. DIAGNOSTIC EVALUATION: Owing to the morphologically and
      functionally complex nature of the lower urinary tract, the diagnostic approach
      to incontinence must involve various levels, and comprises careful history
      taking, a thorough physical examination, and special urodynamic evaluation.
      THERAPEUTIC CONCEPTS: Abundant therapeutic approaches, both pharmacological and
      surgical, are available, but opinion as to what constitutes the best therapeutic
      concept varies greatly. CONCLUSION: Despite the only moderate chances of
      successful treatment under realistic conditions, our present knowledge about the
      diagnosis and treatment of female urinary incontinence needs to become more
      widespread.

PMID- 1398385
TI  - [Duplex ultrasound studies of the portal vein system. Hemodynamic changes in
      liver cirrhosis].

PMID- 1398386
TI  - [Ambulatory surgery. Part 4. Wound management--wound classification].

PMID- 1398387
TI  - [Isotretinoin treatment of acne conglobata. Andrologic follow-up].
AB  - Twenty patients (21.4 +/- 4.3 years) with extensive acne conglobata affecting the
      face, chest and back, were treated for a period of six months with isotretinoin
      (13-cis retinoic acid, 13-cis RA) at a dosage of 1 mg/kg body weight/day (mean
      daily dose 72.7 +/- 9.8 mg 13-cis RA). In all cases, the acne conglobata cleared
      up completely. With the exception of symptoms produced by mucocutaneous
      exsiccation, no side effects were observed; the laboratory parameters were all
      within normal limits during the anti-acne treatment phase. There was no
      recurrence of the disease within a period of one year after cessation of
      treatment (n = 13). Screening spermatograms performed at two-month intervals
      during the treatment phase revealed, from the fourth month of treatment onward, a
      statistically significant increase in the mean sperm density with sperm
      morphology and motility unchanged as compared with the situation prior to
      treatment. One year after conclusion of treatment, all measured spermatogram
      parameters had returned to the initial values. The investigations revealed no
      evidence of any negative influence of the 6-month treatment with isotretinoin on
      spermatogenesis.

PMID- 1398388
TI  - [Renal cell carcinoma--diagnosis, differential diagnosis and prognosis].
AB  - OBJECTIVES: Consideration of the approach to the diagnosis and differential
      diagnosis of renal cell carcinoma and the criteria needed for an assessment of
      prognosis. MAJOR POINTS: Thanks to the comprehensive use of ultrasonography and
      abdominal CT, asymptomatic renal cell carcinomas confined within the renal
      capsule are now more often being discovered and treated by curative surgery. With
      the aid of ultrasonography, abdominal CT and NMR imaging, pre-operative
      visualization of tumor spread is now better, although, with the exception of
      angiomyolipoma, it is still not possible to adequately differentiate the rare
      benign tumors of the kidney, for example oncocytoma, from renal cell carcinomas
      with these procedures. The TNM classification permits a highly differentiated
      prognostic classification of the renal cell carcinomas. The additional prognostic
      parameters, triploidy and hypertetraploidy determinable by flow cytophotometry,
      are also considered. CONCLUSIONS: Early detection of renal cell carcinomas in an
      asymptomatic stage decisively influences the further prognosis, so that for all
      upper abdominal ultrasonographic explorations, performed for whatever reason,
      attention should be paid to such incidental findings.

PMID- 1398389
TI  - [Chances for the success of cytokine therapy in metastatic renal cell cancer].

PMID- 1398391
TI  - [Ambulatory surgery. Part 5: Wound management--tetanus].

PMID- 1398390
TI  - [Concepts in surgical therapy of kidney cancer].
AB  - Three new aspects of the operative treatment of renal cell carcinoma can be made
      out: 1. for the removal of tumor thrombus extending to the right atrium, the
      surgical technique of choice involves whole-body hypothermia and extra-corporeal
      circulation. Only in this way can these tumors be removed completely under good
      vision. 2. Provided the patient's contralateral kidney is healthy, even small
      peripheral renal tumors should be submitted to radical nephrectomy. The rate of
      concomitant small tumors is reported to be as high as 20, while the recurrent
      rate associated with local incision is just on 7%, and the risk of carcinomas
      developing in the contralateral kidney is only 1.8-3.8%. 3. Radical nephrectomy
      for tumor should continue to include the ipsilateral adrenal gland. Although in
      our own patients the incidence of simultaneous adrenal metastasis was only 1.4%,
      if the adrenal gland is left in situ, part of the renal capsule also has to be
      left behind, and the upper pole of the kidney dissected free, with the associated
      risk of disseminating tumor cells.

PMID- 1398392
TI  - [Effect of nilvadipine on diurnal blood pressure profile. Use of a new calcium
      channel blocker in mild to intermediate hypertension].
AB  - QUERY: Influence of Nilvadipine, a new calcium channel blocker on the daytime
      blood pressure profile and 24-hour blood pressure values in patients with mild-to
      moderate hypertension. METHOD: Single-blind study in 20 hospitalized
      hypertensives over a period of 23 days (10 days placebo, 8 days 1 x 8 mg
      Nilvadipine, 5 days placebo). Blood pressure was measured at 7.00 a.m. prior to
      drug ingestion and daytime blood pressure profiles obtained on days 10, 11, 18,
      19 and 23. The objectives were to lower the median diastolic blood pressure or
      daytime blood pressure profiles on the last day vis-a-vis the baseline values,
      and to establish the response rate (blood pressure diastolic less than 90 mmHg)
      24 hours after the last dose of Nilvadipine. RESULTS: After 8 days on
      Nilvadipine, the median diastolic daytime blood pressure profile had decreased by
      almost 10 mmHg. The response rate was 42%. In the same period, the systolic blood
      pressure decreased by 30 mmHg. Six out of 20 patients manifested transient side
      effects typical of calcium channel blockers.

PMID- 1398393
TI  - [Ambulatory cataract operation--a new concept becomes established].
AB  - Outpatient cataract surgery, in particular employing phacoemulsification, has now
      become established practice in Germany. It is as safe as the inpatient procedure
      but for most cataract patients less stressful, cheaper and associated with
      shorter waiting lists. As experience in more than 2,500 cases has shown, the
      outpatient procedure is fully acceptable--also with respect to complications.

PMID- 1398394
TI  - [Recognizing and treating suicidal behavior. Part 1. Results of scientific
      suicide research, relevant for general practice].
AB  - PROBLEM: Whatever his specialty, every medical practitioner will at some time
      encounter patients at risk of suicide. MAJOR TOPICS: Medical research into
      suicide has produced a wealth of knowledge with which the practitioner should be
      familiar if he is to provide such patients with adequate care. Great importance
      attaches to a knowledge of groups at a particularly high risk, of motivations,
      and of the phases of psychodynamic development leading to a suicidal crisis.
      CONCLUSIONS: On the basis of the particular features of the suicide risk, the
      family doctor, who is often consulted shortly before an attempt at suicide is
      enabled to recognize the mental distress of the patient.

PMID- 1398395
TI  - [Self-instruction expert systems in medicine. Presentation of knowledge,
      acquisition of knowledge, prediction of suicide as an example].
AB  - AIMS: 1. Description of how self-learning expert systems work, and 2. comparison
      of various algorithms for the establishment of a data base for suicide
      prediction. POINTS DISCUSSED: from exemplary patient data, self-learning expert
      systems obtain their expert knowledge which they subsequently employ to establish
      the diagnosis in new patients. Various possibilities of storing knowledge may be
      employed, for example the decision tree, classes of rules or neuronal networks.
      The various forms of representing knowledge are also presented. Taking the
      prediction of suicidal risk as an example, the effectiveness of the algorithm is
      tested with the aid of a patient questionnaire. CONCLUSIONS: Different fields of
      application require different systems. The diagnosis of such expert systems can
      at least prompt the care-providing physician to reconsider his own diagnosis.

PMID- 1398396
TI  - [Ambulatory surgery. Part 6: Wound management--rabies].

PMID- 1398397
TI  - [Prevention of coronary heart disease by therapy of hyperlipidemia. Between
      cholesterol hysteria and therapeutic realism].
AB  - OBJECTIVES: The present paper is intended to provide an overview of the arguments
      for and against drug treatment of hyperlipidemia. MAJOR TOPICS: An argument in
      support of lipid-lowering prophylactic and therapeutic programs is the close
      relationship between lipid levels and coronary heart disease, which has been
      documented both epidemiologically and by interventional studies. Arguments
      against comprehensive treatment of hyperlipidemia have to do with the fact that
      although large interventional studies have shown a reduction in mortality from
      coronary heart disease, there has been no reduction in overall mortality. Of
      decisive importance for the decision to apply lipid-lowering treatment is the
      overall risk profile of the patient concerned. This includes not only
      pathological lipid levels, but also numerous other factors that must be taken
      into account when considering the indication. CONCLUSIONS: Whether to initiate
      lipid-lowering treatment or not should be determined on the basis of the
      individual patient's risk profile, with additional consideration being given to
      age and sex.

PMID- 1398398
TI  - [HIV infection increases the rate of tuberculosis. Vaccination--chemotherapy].

PMID- 1398399
TI  - [Recognition and treatment of suicidal risk. Part 2: Diagnostic and therapeutic
      procedure in medical practice].
AB  - The knowledge gained by medical suicide research and clinical experience provides
      a practical basis for diagnostic and therapeutic guidelines for the care
      providing physician. Practical approach: The danger of suicide can be estimated
      on the basis of mental abnormalities and the health or social situation, and the
      level of risk approximately assessed. The appropriate therapeutic approach is
      determined in talks with the patient, which often decide his/her subsequent fate
      and that of the immediate family. The question as to whether to refer the patient
      to institutional psychiatric care--a step that should rarely have to be taken
      against the patient's will--must be carefully considered. CONCLUSIONS: The
      provision of care to suicidal patients on an outpatient basis requires from the
      physician a high level of knowledge, sensitivity and commitment that goes beyond
      mere specialized expertise.

PMID- 1398400
TI  - [TENS: fiction and fact].
AB  - TENS (transcutaneous electrical nerve stimulation) is a widely used therapeutic
      principle that is aimed at ameliorating pain of various genesis. Its
      effectiveness had been more or less accepted, when a study denying this very
      point was published and gave rise to considerable international uncertainty. The
      result was general rejection of TENS (at least in the USA). This reaction is,
      however, certainly not justified. An analysis of the international literature
      shows that most original data are favorable to TENS. It is to be hoped that the
      matter will again receive intensive international research and that within a few
      years we will have identified the indications for this form of therapy.

PMID- 1398401
TI  - [How (un)toxic is tamoxifen? Risks and side effects during its use].

PMID- 1398402
TI  - [Life-threatening hyponatremia. Part 1: Diagnosis of hypotonic dehydration and
      hyperhydration].

PMID- 1398403
TI  - [Effect of acarbose on injection-eating interval in type I diabetes. Preliminary
      contribution].
AB  - In a pilot study, 7 patients with Type I diabetes received three daily doses of
      100 mg acarbose for three days within the framework of intensified insulin
      therapy. At the same time, the 30 minute interval normally observed between
      injection and eating was abandoned. The blood glucose levels measured one hour
      post-prandial in diabetics taking acarbose and not observing the injection-eating
      interval were lower than those measured prior to acarbose and while observing the
      interval. Large-scale controlled studies are needed to investigated the theory
      that in insulin-dependent diabetics taking acarbose, observation of the injection
      eating interval can be abandoned.

PMID- 1398405
TI  - [Climate therapy--more than the "right" climate. Prevention--cardiac
      rehabilitation].

PMID- 1398404
TI  - [Didanosine as an alternative for HIV infection. AIDS--disease progression].

PMID- 1398406
TI  - [Strategies against AIDS have hardly progressed. Are cancer prevention programs
      suitable as a model?].

PMID- 1398407
TI  - [Ambulatory follow-up care in laparoscopic cholecystectomy].
AB  - FUNDAMENTAL CONSIDERATIONS: With increasing frequency, laparoscopic procedures
      are now replacing conventional cholecystectomy. Given the choice, patients with
      cholecystolithiasis almost always opt for the former procedure. MAJOR POINTS:
      Because the laparoscopic procedure offers considerable advantages as compared
      with open surgery, the increased risk of local complications associated with it
      tends to be ignored. For example, injuries to the biliary ducts are about ten
      times as common as in the case of conventional cholecystectomy. Injuries to the
      bowel, previously unknown, are increasingly being observed. Symptoms associated
      with undetected injuries usually do not occur until the patient has been
      discharged. CONCLUSIONS: Ambulatory aftercare is particularly important following
      laparoscopic cholecystectomy. Complications need to be detected in good time in
      order to be able to institute appropriate counter-measures.

PMID- 1398408
TI  - [Methodological deficiencies in clinical trials].
AB  - In many cases, the results obtained with clinical trials are out of all
      proportion to the time, money and effort invested by those participating in them.
      The reasons for this are to be sought, for the most part, in readily avoidable
      errors at the planning stage, during evaluation and during preparation for
      publication. Common weak points prove to be the design of the trial, patient
      numbers, selection of end points, characteristics of case material, blinding,
      randomization, exclusion from evaluation, test efficiency (power 1-beta),
      subgroup analyses and interim analyses.

PMID- 1398409
TI  - [Chronic gastritis--does it need treatment and is it curable?].
AB  - FUNDAMENTAL CONSIDERATIONS: Addition to our medical knowledge of chronic
      gastritis and its sequelae; changes in nomenclature. METHODS/CONTENT:
      Presentation of the pathophysiological situation (processes) oft colonization of
      the gastric mucosa by Helicobacter pylori with particular consideration being
      given to histomorphological findings. Discussion of the relative risk of
      gastritis patients contracting a gastric or duodenal ulcer, or possibly
      developing carcinoma of the stomach. CONCLUSIONS: On account of the possible
      sequela of ulcer and its potential complications, and also the presumably
      elevated risk of carcinoma, Helicobacter pylori associated chronic gastritis
      should be submitted to a diagnostic work-up and then treated.

PMID- 1398410
TI  - [The OPM syndrome (Occult primary malignancy)--malignancy with unknown primary
      tumor. 1: Diagnostic procedures].

PMID- 1398411
TI  - [Effects of cholecystokinin and its antagonists on the GI tract. Potent
      inhibition of gastrointestinal motility by loxiglumide].

PMID- 1398412
TI  - [Gemfibrozil in the differential therapy of disorders of fat metabolism].
AB  - In addition to high concentrations of LDL cholesterol, high levels of
      triglycerides and low concentrations of HDL cholesterol are now known to be
      independent risk factors in the development of atherosclerosis. The use of
      Gemfibrozil, with its LDL cholesterol-reducing, HDL cholesterol-raising, and
      triglyceride-lowering effects, would thus appear to make good sense for the
      treatment of lipid metabolism anomalies with no selective elevation of LDL
      cholesterol; it would thus also appear to be superior to HMG-CoA-reductase
      inhibitors.

PMID- 1398413
TI  - [Advances in the treatment of lipid metabolism disorders. Role of CSE-inhibitors.
      Report from the 11th International Symposium on Drug Affecting Lipid Metabolism.
      Florence, 13-16 May 1991].

PMID- 1398414
TI  - [The history of German psychiatry from the viewpoint of French psychiatrists].
AB  - The reception of German psychiatry by the French psychiatrists has been
      influenced by material elements, such as the knowledge of the German language
      and/or the disposability of translations, but even more by factors of a general
      nature. The main reason has been the perception by the French psychiatrists of
      the progressive loss of influence of their own school, initially the leading one
      in the world, in favour of the German, a change which began with Griesinger and
      became evident at the time of Kraepelin. Around 1850, as demonstrated by many
      papers written by leading French psychiatrists, the interest both for the
      theoretical aspects of German psychiatry and for its care system was great. The
      judgements were extremely positive, although French authors tended to contrast
      the philosophical outlook of the Germans with their own concrete clinical
      approach. The war of 1870-71 produced no radical change. But the growing
      influence of German psychiatry induced negative reactions whose main target was
      the work of Kraepelin, and especially his synthesis of Dementia praecox which was
      in direct opposition with the then dominant concepts of Magnan. The French
      opinion was divided between defenders and adversaries of Kraepelin's ideas. In
      the years immediately preceding World War I the attacks increased. The alleged
      contrast between the descriptive clinical (and according to a German author like
      Jaspers literary and superficial) French psychiatry and the scientific
      theoretical (and for the most aggressive French authors valueless) German one was
      a recurrent theme. The nationalistic tone reached on the French side its apex
      during the war years, some faint traces remaining several years after 1920. But
      on the whole the influence of the concepts proposed by German speaking authors,
      not only Kraepelin, but also Bleuler, Kretschmer, Freud among others was then on
      the increase. After 1945, contrasting with the years after World War I, no
      hostility against German psychiatry can be detected, as testified by the choice
      of the main speakers by the French organizers of the First World Congress of
      Psychiatry in 1950. The creation in 1984 of the Association of European
      Psychiatrists, an initiative taken jointly by the French and German
      psychiatrists, can be considered as the symbolic conclusion of the relations
      between the two national schools.

PMID- 1398415
TI  - [Important asylums in France, Germany and England (1800-1900)].
AB  - This study contains a list of the most significant institutions for the care of
      the insane and also, at a later date, for mentally ill patients. We had to
      restrict it to the 19th century only and to the areas of Europe where French,
      German and English are spoken. Many of the most renowned psychiatrists and their
      publications are classified according to the asylums where they worked. The
      author refrained on purpose from any analysis or interpretation, glorifying
      encomiums or accusations, because from the scientific point of view it is more
      important to place on record the many names, dates and above all the
      architectural structures of monuments before they get fallen into oblivion.

PMID- 1398416
TI  - [Endangerment and dangerousness of psychiatry].
AB  - Psychiatry is more influenced by the "Zeitgeist" than other medical disciplines.
      One important reason is the lack of biological data despite large efforts. In
      this situation ideological factors may become more relevant than they deserve.
      Temptations of a "pure" doctrine are dangerous. New developments (methadone
      substitution, active euthanasia) add to the possible dangerousness of psychiatry.
      Psychiatrists will have to be careful to avoid this dangerousness and the
      endangering of their discipline.

PMID- 1398417
TI  - [Introduction of shock therapy and psychiatric emigration].
AB  - The introduction and general acceptance of shock treatment was intimately
      connected with the emigration of psychiatrists from the German speaking countries
      in 1933-1938. In 1934 Manfred Sakel began in Vienna, possibly already in 1933 in
      Berlin, with insulin shock treatment, and later emigrated to the US. From 1936
      Max Muller in Munsingen, Switzerland, practised and propagated the same
      treatment. Many psychiatric emigrants, on their way to their new countries,
      visited Munsingen to learn the methods and take them to their future countries of
      residence (e.g. Lucie Jessner, Gertrude May-Gross, Martin Gross, Ruth Wilmanns,
      Arthur Kronfeld, Justin Hans Adler and Jacob Peter Frostig). In 1934 Ladislas von
      Meduna, who emigrated to Chicago in 1939, using campher and Cardiazol also
      introduced the convulsion treatment. After Cerletti and Bini in Rome had changed
      the method of provoking convulsions by using electric current, other psychiatric
      emigrants (Lothar Kalinowsky, Fritz Kant, William Karlinger, Lilly Ottenheimer,
      Max Rinkel, among others) introduced this method to many countries. In addition,
      Wagner-Jauregg's best known collaborators for the well-introduced malaria
      therapy, also had to emigrate. Among these are Helene Deutsch, Josef Gerstmann,
      Bernhard Dattner and Martha Brunner-Ornstein. The review of life and work of the
      psychiatrists concerned, before and after emigration, has been complemented by
      unpublished material.

PMID- 1398418
TI  - [Jubilee congress of the DGPN. German Society for Biological Psychiatry. 150
      years of psychiatry. A multiform psychiatry for the world of tomorrow. 26-30
      September 1992, Cologne. Abstracts].

PMID- 1398419
TI  - My experience as a courier.

PMID- 1398420
TI  - [Endothelium derived relaxing factor].

PMID- 1398421
TI  - Utility of the latex agglutination nephelometric immunoassay (Albusure Test) in
      screening for microalbuminuria in patients with diabetes mellitus.
AB  - All diabetic patients should be screened for early signs of diabetic nephropathy,
      because it is a prognostic factor in the disease. The albusure test (AT), a latex
      agglutination nephelometric immunoassay, is a rapid and low cost test for the
      detection of microalbuminuria of 30 mg/L or more. We compared the results of AT
      and of radioimmunoassay (RIA) for urinary albumin to evaluate the clinical
      utility of AT using fresh urine samples from 74 diabetic patients without
      persistent proteinuria and from 11 healthy subjects. Urinary albumin levels were
      6.0 +/- 2.3 mg/L in the healthy subjects, 11.0 +/- 8.7 mg/L in the AT-negative
      group (n = 61), and 38.1 +/- 10.2 mg/L in the AT-positive group (n = 13). Using a
      cut-off value of 30 mg/L by RIA, the rate of coincidence between AT and RIA was
      89.2%, although five subjects were false-positive by AT, and three were false
      negative. These results show that AT may provide a useful monitor for
      microalbuminuria, a reliable early marker of diabetic nephropathy.

PMID- 1398422
TI  - [Clinical evaluation of the intraluminal ultrasonography].
AB  - Although for the diagnosis of rectal diseases barium-enema and colonoscopy have
      been commonly carried out, by the methods neither information on the layer
      structure of the intestinal wall nor swelling of the regional lymphnodes can be
      provided. Therefore we tried intraluminal ultrasonography (IUS) for further
      evaluation of the rectum and peri-rectal lesion, and the usefulness of IUS in the
      rectal disease was described. In 46 cases of rectal cancer, the following results
      were obtained. Five layer structures were distinguished in the normal rectal wall
      by the IUS. Intraluminal invasion showed destruction of the layer structures of
      the colonic wall. The swelling of the regional lymphnodes was revealed as low
      echoic round mass. In 43 cases with benign diseases, characteristic variations of
      the layer structures in the colonic wall can be distinguished by the IUS. In
      conclusion, the IUS was of great use to observe the variation of the layer
      structure of colonic wall and to provide valuable information on metastasis into
      the regional lymphnodes.

PMID- 1398423
TI  - [A case of obstructive ileus following the upper Gi barium swallow study with
      condensed barium due to severe constipation].
AB  - A 64-year-old woman visited my clinic with complaints of abdominal distension,
      constipation, and nausea. Since abdominal X-ray showed severe obstructive ileus
      following the upper GI barium swallow study, the patient was sent immediately to
      Saga Medical School Hospital for the emergency operation. As the result of the
      left hemicolectomy, two obstructive lesions were found at the sigmoid colon and
      the transverse colon. Nowadays, as the population of aged people increases and
      Japanese diet changes, colon cancers are increasing more rapidly. Since the half
      of colon cancers doesn't have any clinical symptoms of obstruction, the upper GI
      barium swallow study with condensed barium might lead a patient to some type of
      dangerous situation.

PMID- 1398424
TI  - [Successful intrauterine digoxin therapy for fetal complete atrioventricular
      block with endocardial cushion defect: a case report].
AB  - We report herein a case of fetal complete atrioventricular block accompanied with
      endocardial cushion defect, successfully diagnosed and treated, in utero, with
      transplacental digitalization. A 23-year-old Japanese woman, at 20 weeks of
      gestation, was referred to the Maternity and Perinatal Care Unit of Kyushu
      University Hospital because of fetal continuous bradycardia. B-mode scanning and
      dual M-mode echocardiography revealed that the fetus had complete
      atrioventricular block with endocardial cushion defect with a ventricular rate of
      60 beats per minute. At 23 weeks of gestation, it was found that the fractional
      shortenings (FSs) in both ventricles and the ventricular rate had decreased, with
      an increase in pericardial effusion. Thus, we diagnosed the fetus as having
      cardiac failure. Transplacental digoxin treatment was started and continued for
      10 weeks, after which fetal pericardial effusion, as well as FSs ameliorated. The
      pregnancy was interrupted by cesarean section at 33 weeks of gestation due to a
      decrease in FSs with an accumulation of fetal ascites. A 1780g female infant was
      delivered and a pacemaker was implanted surgically, immediately after birth. She
      is alive and well at the time of writing.

PMID- 1398425
TI  - [A case of hyperparathyroid bone disease and the review of renal osteodystrophy].
AB  - We report here a typical case of hyperparathyroid bone disease associated with
      CRF on maintenance HD and review on Renal Osteodystrophy. A 39 year-old female
      patient was admitted because of polyarthralgia and pruritus. She had a history of
      HD due to CGN for about 13 years. Laboratory data showed an increase in serum PTH
      and Alkaline phosphatase level. The evidence of osteitis fibrosa was revealed by
      bone Xp and scintigraphy. Enlarged solid masses were found in her neck by
      echogram and parathyroid scintigraphy. She was diagnosed as hyperparathyroid bone
      disease and total parathyroidectomy c autoplantation was done. Shortly after the
      surgical treatment, subjective symptoms were relieved and PTH level was
      normalized. The bone Xp findings improved gradually.

PMID- 1398426
TI  - [Senile osteoporosis in normal women examination using dual energy X-ray
      absorptiometry].
AB  - Osteoporosis is now one of the most serious problems in aged Japanese women. We
      investigated bone mineral contents of the vertebrae of 132 adult women (28
      94y.o.) using dual energy X-ray absorptiometry (DEXA) in order to clarify the
      change of the bone mineral densities (BMD) with aging, and the influences of a
      diet and exercise on osteoporosis. In the women, BMD of the vertebrae increase to
      maximum level in 3 rd or 4 th decade of life, and then reduce with aging. The
      level of BMD is well matched with the index of osteopenia using the lateral view
      of vertebral X-ray. According as the BMD reduce, the number of bone fractures and
      the number of patients with bone fractures increase. More than 80% of the women
      whose BMD are less than 0.7 g/cm2 have bone fractures. In aged women, over 65
      year's old, exercise had significant positive effect with BMD, but that was no
      evidence for influence of calcium intake to BMD.

PMID- 1398427
TI  - [Jaw movement and the cortico-mesencephalic pathway].

PMID- 1398428
TI  - How blood viscosity influences changes in circulation during pregnancy?
AB  - The changes of whole blood viscosity and plasma viscosity were studied in 15
      normal non-pregnant women, and 120 normal pregnant women ranging from 8 to 39
      weeks of gestation. The values of whole blood viscosity during normal pregnancy
      were significantly lower from 20 to 31 weeks of gestation than those in the other
      periods of gestation, and there was a positive correlation between whole blood
      viscosity and hematocrit. Plasma viscosity, however, did not change significantly
      during pregnancy. There was no correlation between whole blood viscosity and
      plasma viscosity, and there was also no correlation between plasma viscosity and
      plasma fibrinogen concentration. These findings suggest that decreases in whole
      blood viscosity, resulting from the change of packed-cell volume, may strongly
      contribute hemorheologically to the decrease in peripheral resistance during the
      second trimester.

PMID- 1398429
TI  - [Effective continuous hemofiltration and plasma exchange for the treatment of
      subacute type fulminant hepatic failure].
AB  - By combination of continuous hemofiltration (CHF) with plasma exchange therapy we
      successfully treated a patient with subacute type fulminant hepatitis to keep her
      consciousness alert. The patient was a 55-year-old woman who admitted because of
      severe jaundice. On the 51st day after the onset she had consciousness
      disturbance and was transferred to our hospital. We started the therapy of CHF
      and plasma exchange at the patient's hepatic coma grade 4. On the 5th day her
      consciousness level recovered to grade 2 and we could keep the level for almost 2
      weeks. This combination therapy seemed good not only for the improvement of
      consciousness of patients in hepatic coma but also to support the hepatic
      function of almost ahepatic patients.

PMID- 1398430
TI  - The history of right heart bypass before Fontan.
AB  - Numerous clinical and experimental studies have suggested that adequate pulmonary
      blood flow and normal central venous pressure may be maintained without
      significant contribution of right ventricular function. These data induced
      experimental and clinical research in the quest for complete bypass of the right
      heart. More than 40 different operations have been designed to bypass the right
      ventricle. Partial right ventricular bypass was achieved in 1949 by anastomosing
      the superior vena cava to the pulmonary artery in animal experiments. In 1950
      such as operation was successfully performed clinically for the first time.
      Complete bypass of the right heart was accomplished for the first time
      experimentally in 1954 by performing a superior vena cava-to-right pulmonary
      artery anastomosis and implanting the inferior vena cava into the left atrium.
      Successful clinical bypass of the right heart was carried out later by implanting
      both vena cavae into the pulmonary circulation. Until the cavopulmonary shunt
      conclusively proved the validity of the concept that compensated circulation is
      possible without participation of the right ventricle, surgeons did not fully
      understand its possible relevance in clinical situations. The development of
      partial and complete right heart bypass procedures, both experimental and
      clinical, not only presented us with viable alternatives to aortopulmonary shunts
      like the Blalock-Taussig or Potts anastomosis, but it also opened the way to
      development of new operations such as the Fontan procedure which are based on the
      principle of low pressure pulmonary flow and right ventricular bypass.

PMID- 1398431
TI  - Pre-operative assessment of ventricular function in patients considered for
      Fontan procedure.
AB  - In 1978 Choussat and Fontan established ten criteria, which should be fulfilled
      to achieve a successful outcome in Fontan operation. Recent data suggest that
      while some of these ten criteria need not be necessarrily be fulfilled, new
      criteria should be added. These include 1. good diastolic function, 2. normal or
      only slightly increased ventricular mass, and 3. absence of systemic outflow
      obstruction. In addition the morphology of the single ventricle may be important
      as long-term results in patients with single ventricle of right ventricular
      morphology may be worse than results in patients with single ventricle of left
      ventricular morphology. Ventricular size and pump function can be assessed by
      cardiac catherization, echocardiography or magnetic resonance imaging. Estimation
      of ejection fraction under stress by nuclear angiography may be indicated.
      Diastolic function can be examined using Doppler echocardiography or nuclear
      angiography. Myocardial mass may be assessed by echocardiography or magnetic
      resonance imaging. Normal reference values for different parameters of systolic
      and diastolic function are listed in the enclosed tables. Patients scheduled for
      a Fontan operation should have an ejection fraction less than 50%. Patients with
      borderline ejection fraction should be examined by echocardiography to determine
      the end-systolic wall stress, a parameter of ventricular contraction, which is
      independent of pre- and afterload. As afterload may decrease after a Fontan
      operation some patients with reduced ejection fraction but normal end-systolic
      wall stress may still be suitable candidates for Fontan operation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1398432
TI  - The relation between ventricular hypertrophy and clinical outcome in patients
      with double inlet left ventricle after atrial to pulmonary anastomosis.
AB  - To clarify differences between pre- and postoperative volumetric and hemodynamic
      variables from patients with clinically good and poor outcomes after a Fontan
      procedure, 40 patients with univentricular heart (double inlet left ventricle)
      (mean age: 5.7 +/- 3.3 years) were studied using the ventricular cineangiography.
      According to postoperative clinical findings, patients were classified into two
      groups: 26 patients with good outcomes and 14 patients with poor outcomes
      (including five with early and two with intermediate deaths) and compared with a
      control population. Age at surgery, pre-operative cardiac index, wall mass and
      systolic ejection phase parameters were not different between the two patient
      groups, however, end-diastolic volume index in poor outcomes was significantly
      smaller than those with good outcomes (100 +/- 24, 78 +/- 22, 64 +/- 14 ml/m2:
      good, poor outcomes and controls, respectively, p less than 0.05), and the
      mass/volume ratio in this group significantly elevated (1.00 +/- 0.18, 1.19 +/-
      0.33, 0.97 +/- 0.19 g/ml, p less than 0.05). Postoperatively, both ventricular
      volume and mass in good outcomes returned toward the normal and the mass/volume
      ratio remained within normal range (1.07 +/- 0.22). In contrast, the
      hypertrophied ventricular mass in those patients with poor outcomes did not
      decrease in parallel with ventricular volume, thus contributing to a further
      increased ratio (1.48 +/- 0.19). Although there were no significant differences
      between pre-operative hemodynamic variables among the two groups, the mass/volume
      ratio in those with poor outcomes was increased pre-operatively and further
      increased after the Fontan procedure due to rapid and acute reduction of
      preload.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398433
TI  - Pathophysiological and metabolic manifestations of pulmonary vascular disease in
      children.
AB  - In children with congenital heart disease pulmonary vascular disease can be fatal
      for a variety of reasons. Even before the classical changes of advanced pulmonary
      vascular obstructive disease have developed, a marked increase in pulmonary
      vascular smooth muscle can be fatal due to pulmonary hypertensive crises. After
      the Fontan procedure, a modest increase in muscularity can jeopardise the outcome
      since there is no subpulmonary ventricle to support the pulmonary circulation.
      Following heart transplantation, a slight increase in muscularity can cause
      failure of the donor right ventricle unless that heart is already hypertrophied
      as in the domino procedure. In all children with pulmonary hypertension, either
      persistent pulmonary hypertension of the newborn or secondary to congenital heart
      disease the pulmonary vasculature fails to remodel normally after birth. Newborn
      vessels are characterized by the immaturity of the smooth muscle cells and the
      paucity of connective tissue. In the hypertensive lung smooth muscle
      differentiation and connective tissue deposition is accelerated. In children with
      congenital heart disease intimal changes follow. In these children the potential
      reversibility of disease following intracardiac repair is determined by the type
      of pathological change present at the time of repair. However, pulmonary
      hypertensive crises can occur in young children with potentially reversible
      disease. Operability is not synonymous with the potential reversibility of
      pathological lesions. Correlations between structural findings at lung biopsy and
      haemodynamic findings at cardiac catheterization have improved the accuracy with
      which the natural and unnatural history of pulmonary vascular disease can be
      predicted, but is still inadequate because we do not understand the functional
      implications of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398434
TI  - Promoting and sustaining the health of the mind.

PMID- 1398435
TI  - Challenges for child and adolescent mental health.

PMID- 1398436
TI  - Insurance coverage for drug abuse.

PMID- 1398438
TI  - Pharmacology: policy implications of new psychiatric drugs.

PMID- 1398437
TI  - Treating depression and anxiety in the primary care setting.

PMID- 1398439
TI  - Psychiatric rehabilitation: key issues and future policy.

PMID- 1398440
TI  - On the abolishment of the case manager.
AB  - Stabilizing clients in the midst of a psychotic episode in the hospital can be a
      difficult task that requires a multidisciplinary team. The task of helping those
      persons to live stable lives of decent quality after they leave the hospital is
      at least as difficult, and much more complex. Thus, it is not surprising that the
      case management model, which is not multidisciplinary and is available only on
      weekdays, is inadequate to deliver well-integrated, constantly available services
      to difficult clients. The effect on clients is that few are receiving adequate
      rehabilitation, and many are unstable and frequently rehospitalized. The effect
      on the system is that a large portion of the mental health budget goes to
      hospital care, frustrating attempts to reallocate dollars to develop
      comprehensive services in the community.

PMID- 1398441
TI  - Patterns of use and costs among severely mentally ill people.

PMID- 1398442
TI  - Public attitudes toward persons with mental illness.

PMID- 1398443
TI  - Impact of managed care on mental health services.

PMID- 1398444
TI  - A five-nation perspective on the elderly.

PMID- 1398446
TI  - Observations from the program on chronic mental illness.

PMID- 1398445
TI  - Impact of the Medicare physician fee schedule.

PMID- 1398447
TI  - Measuring the need for mental health care.

PMID- 1398448
TI  - The Americans with Disabilities Act and the U.S. health system.

PMID- 1398449
TI  - Return to constructive debate on U.S./Canadian health spending.

PMID- 1398450
TI  - A case for community rating.

PMID- 1398451
TI  - Case management in Washington, D.C.

PMID- 1398452
TI  - Challenges in state mental health policy and administration.

PMID- 1398454
TI  - New futures for mental health care: the case of Ohio.

PMID- 1398453
TI  - Lessons from the program on chronic mental illness.

PMID- 1398455
TI  - Mental health policy in America: myths and realities.

PMID- 1398456
TI  - Reform issues for insuring mental health care.

PMID- 1398457
TI  - A model mental health benefit in private health insurance.

PMID- 1398458
TI  - Recent advances in studies of the molecular basis of endocrine disease.
AB  - The molecular basis for a number of endocrine disorders has been determined in
      the last several years. Mutations have been described at multiple different steps
      in the pathways of hormone action. There are now examples of mutations in
      hormones themselves, hormone receptors, second messenger signalling pathways, and
      the transcription factors that transduce hormone signals. Several common themes
      emerge even from the relatively small number of mutations that have been
      described to date. First, the phenotypic variability that characterizes many
      endocrine diseases is also reflected in genetic heterogeneity. Some clinical
      phenotypes that were thought previously to represent distinct diseases can now be
      interpreted as manifestations of different types of mutations within a single
      gene. Second, the propensity of certain genes to be targets for frequent
      mutations may be explained in part by gene structure and organization. Third,
      although many of the mutations reported initially have been associated with
      severely affected patients, it is likely that mutations with less severe
      consequences will also be identified. Genetic polymorphisms within the normal
      population could also cause subtle differences in hormone or receptor activity,
      thereby constituting part of the basis for variability in hormone levels and
      activity. Finally, one can predict continued rapid advances in this field with
      transfer of genetic testing into clinical practice in the near future.

PMID- 1398459
TI  - The role of ras proteins in insulin signal transduction.
AB  - Ras-proteins are guanine nucleotide binding proteins, which, in the GTP bound
      state emit a strong mitogenic signal. In the GDP bound state, the protein appears
      inactive. We have found that stimulation by insulin of cells expressing elevated
      levels of insulin receptors results in a rapid conversion of Ras-GDP into Ras
      GTP. This process is part of the signalling pathway leading to immediate-early
      gene expression and a mitogenic response. There seems to be no involvement of Ras
      GTP formation in the process of insulin stimulated glucose transport. Though the
      precise mechanism by which Ras is converted to the GTP bound state remains to be
      established, a tight correlation exists between receptor autophosphorylation and
      Ras-GTP formation.

PMID- 1398460
TI  - Pathophysiological aspects of non-tyrosine kinase signal transduction.

PMID- 1398461
TI  - Insulin, at physiological concentrations, enhances the polymorphonuclear
      leukocyte chemotactic properties.
AB  - We investigated the influence of insulin on human polymorphonuclear leukocyte
      (PMN) chemotaxis induced by mediators in a microchamber assay. Insulin increased,
      with a dose-response relationship, chemotaxis induced by formyl-methionyl-leucyl
      phenylalanine, calcium ionophore and phorbol-miristyl acetate (p = 0.0057, p =
      0.0001 and p = 0.0215, respectively). The hormone effect was present also at the
      physiological concentration of 40 microU/ml. Our data show that insulin affects
      PMN activity in normal subjects and therefore support the hypothesis that insulin
      deficiency may be responsible for the impaired PMN function observed in diabetic
      patients in poor metabolic control.

PMID- 1398463
TI  - Differential effect of adrenalectomy on rat liver metallothionein mRNA levels in
      basal and stress conditions.
AB  - Liver metallothionein (MT) mRNA and serum MT levels of adrenalectomized (ADX) and
      sham-ADX rats in basal and stress (1, 3 or 6 h of restraint) conditions have been
      measured. Serum MT levels were overall lower in ADX than in sham-ADX rats. Basal
      liver MT mRNA levels were increased in ADX rats, suggesting that glucocorticoids
      have an inhibitory role on the regulation of liver MT synthesis. In contrast,
      liver MT mRNA levels were increased by stress in sham-ADX but not in ADX rats,
      suggesting a stimulatory role for glucocorticoids. These results suggest that
      glucocorticoids have a different role in liver MT regulation depending on the
      physiological situation.

PMID- 1398462
TI  - Effect of melatonin on pulsatile release of luteinizing hormone in female lambs.
AB  - This study investigated the effect of melatonin treatment of ewe lambs on LH
      pulsatility in an attempt to examine the mechanism whereby melatonin advances the
      onset of puberty. Six ewe lambs were given intravaginal melatonin implants at
      12.8 weeks of age. Another six lambs received empty implants. All lambs were
      serially blood sampled every 15 minutes for six hours on several occasions prior
      to the onset of puberty. One week after implantation LH pulse frequency and mean
      LH levels were higher in treated lambs than the control lambs (pulse frequency
      0.13/h vs 0.03/h; mean LH levels 2.0 +/- 0.2 ng/ml vs 1.3 +/- 0.1 ng/ml; p less
      than 0.05). Melatonin treatment failed to alter pulse frequency after the initial
      increase. Puberty was advanced by 3 weeks in the treated group. In the second
      experiment six lambs received melatonin implants at 13 weeks of age and another
      six lambs served as control. In this experiment blood samples were taken
      intensively during the first few weeks after treatment. Results of this study
      show that mean plasma LH levels and LH pulse frequency were again higher during
      the first week after implantation. This transient increase in LH release may be
      part of the mechanism initiating the eventual advancement of puberty although the
      significance of this increase is questionable. In both experiments the LH
      response to estradiol injection was monitored at various times after treatment,
      but no effects of melatonin were found, although the magnitude of the response
      increased with age.

PMID- 1398464
TI  - SMS 201-995 and thyroid function in acromegaly: acute, intermediate and long-term
      effects.
AB  - The acute (TRH-stimulation test), intermediate (0-6 days administration), and
      long-term (0-30 months administration) effects of SMS 201-995 (octreotide)
      treatment on thyroid function were studied. Subcutaneous injection of 100
      micrograms SMS 201-995 one hour before 200 micrograms TRH intravenously reduced
      serum TSH response area by more than 50% in 8 healthy volunteers. After 3 days of
      continuous subcutaneous infusion (CSI) of SMS 201-995 in 9 acromegalic patients
      (100 micrograms/24 h) a slight but significant decrease in serum total
      triiodothyronine (TT3) and a concomitant increase in serum TSH were demonstrated,
      indicating an initial inhibitory effect on peripheral deiodination of thyroxine.
      After a further 3 days treatment serum T3 and TSH had returned to prevalues. Six
      of the nine acromegalics were treated with SMS 201-995 (100-1500 micrograms/24 h)
      and admitted for diurnal hormone profiles on 13 occasions over 30 months. Apart
      from a barely significant increase in serum TSH, no changes in thyroid function
      were noted. The study was especially designed to detect minute changes over time
      in thyroid hormones. The only long-term effect of SMS 201-995 was the barely
      significant clinically irrelevant increase in serum TSH, possibly caused by a
      slight inhibition of peripheral deiodination of thyroxine.

PMID- 1398465
TI  - Comparative effect of clonidine and growth hormone (GH)-releasing hormone on GH
      secretion in adult patients on chronic glucocorticoid therapy.
AB  - Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an
      enhancement of endogenous somatostatin tone. The aim of our study was to evaluate
      the effects of GH-releasing hormone (GHRH) and clonidine, an alpha-2-adrenergic
      agonist which increases GH secretion acting at the hypothalamic level with an
      unknown mechanism, on GH secretion in seven adult patients (3M, 4F) with non
      endocrine diseases and on daily immunosuppressive glucocorticoid therapy. Eleven
      normal subjects (7M, 4F) served as controls. Steroid-treated patients showed a
      blunted GH response to GHRH (GH peak 8.3 +/- 3 micrograms/L) with respect to
      normal subjects (GH peak 19.3 +/- 2.4 micrograms/L). The GH responses to
      clonidine were also blunted (p less than 0.05) in steroid-treated patients (GH
      peak 5.8 +/- 2.8 micrograms/L) with respect to normal subjects (GH peak 17.6 +/-
      2.3 micrograms/L). No significant differences between the GH responses to GHRH
      and clonidine were observed either in steroid-treated or in normal subjects.
      Clonidine is not able to enhance GH secretion similar to GHRH in patients
      chronically treated with steroids. It can be hypothesized that clonidine does not
      elicit GH secretion decreasing hypothalamic somatostatin tone.

PMID- 1398466
TI  - Effect of the aquaretic vasopressin antagonists d(CH2)5[D-Tyr(Et)2-Val4]AVP and
      d(CH2)5[D-Phe2-Phe4]AVP on urine production in healthy dogs.

PMID- 1398467
TI  - Plasma of Walker-256 carcinosarcoma bearing rats contains parathormone related
      peptide.

PMID- 1398468
TI  - Effect of pretreatment with pyridostigmine on the thyrotropin response to
      thyrotropin-releasing hormone in patients with Cushing's disease.

PMID- 1398469
TI  - Endocrine disorders in 66 suprasellar and pineal tumors of patients with
      prepubertal and pubertal ages.
AB  - Tumor oncotypes, initial symptoms and endocrine disturbances before and/or 1
      month after surgery were studied in 66 patients with prepubertal and pubertal
      ages having suprasellar or pineal intracranial tumors. Neoplasms found in
      patients of prepubertal age were: 15 craniopharyngiomas (CRA), 24 neuroepithelial
      cell-derived tumors (NEC), 5 germ cell tumors (GERM) and 4 other lesions (OTHER).
      In patients of pubertal age, there were 7 CRA, 7 pituitary tumors (PIT), 2 NEC, 1
      GERM and 1 OTHER. Approximately 90% of patients had visual abnormalities as one
      of the initial signs and symptoms, while 59% had increased intracranial pressure.
      Short stature was observed in only 10% of patients. Before surgery, somatotropic
      function was found to be deficient (by 2 pharmacological tests) in 90-100% of
      patients with CRA, PIT or GERM and in 40% of patients with NEC. Overt
      hypothyroidism was found in 5-25% of CRA, NEC or GERM but in 40% of PIT. Abnormal
      TSH responses to TRH were observed in 64% of CRA and in 29% of NEC. Low basal
      serum cortisol was found in 21 or 6% of patients with CRA or NEC, but in 100 or
      60% of patients with PIT or GERM, respectively. Diabetes insipidus was diagnosed
      in 13.6% of all patients. Surgery produced few additional disturbances in
      endocrine function, except for the incidence of diabetes insipidus which was
      doubled. Gonadotropic deficiency was found in most patients of pubertal age with
      CRA and PIT. They were readily differentiated by the high prolactin or growth
      hormone (GH) levels of the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398470
TI  - Growth hormone response to thyrotropin-releasing hormone in acromegalic patients:
      reproducibility and dose-response study.
AB  - The aim of the study was to analyze 14 consecutive patients with active
      acromegaly who had not undergone any therapy, the dose response of growth hormone
      (GH) to thyrotropin-releasing hormone (TRH), the existence of reproducibility of
      such response as well as to rule out the possibility of spontaneous fluctuations
      of GH which would mimic this response. On several nonconsecutive days, we
      investigated the GH response to saline serum, 100, 200 (twice) and 400 micrograms
      of TRH administration. We also studied both basal serum prolactin, serum
      prolactin after TRH administration and thyrotropin values. Our results show an
      absence of GH response after saline serum infusion, whereas after TRH doses, 36.3
      42.8 and 45.4% positive responses were obtained, respectively. All GH responders
      were concordant to the different doses administered. The mean of GH
      concentrations of the different doses at different times did not reach
      significant differences. The response to the administration of the same dose
      brought about a significative increase, although it was not identical. It
      demonstrated a progressive increase of the area under the response curve, as did
      the means of increments after each TRH administration, albeit without reaching
      statistical significance. Between the GH-responding and GH-nonresponding groups
      there were no differences in either basal serum prolactin or serum prolactin and
      thyroid-stimulating hormone levels after TRH stimulation. The present study
      clearly shows that TRH elicits serum GH release from GH-secreting pituitary
      tumors. The response was reproducible in qualitative terms rather than
      quantitative, and no dose-response relationship was found between the TRH
      concentrations and the amounts of GH secreted.

PMID- 1398472
TI  - Histology of skeletal muscle in adults with GH deficiency: comparison with normal
      muscle and response to GH treatment.
AB  - The histology of needle biopsy specimens of skeletal muscle from the vastus
      lateralis was quantitatively assessed in a group of adults with growth hormone
      (GH) deficiency, most of whom had hypopituitarism treated with conventional
      pituitary hormone replacement. The mean age of the 21 patients (16 males and 5
      females) was 39 +/- 2 (SEM). Comparisons were made with age- and sex-matched
      controls following six months double-blind, placebo-controlled treatment with
      recombinant human GH (rhGH) in the GH-deficient patients. Before treatment,
      needle muscle biopsies from patients with GH deficiency showed mean type I and II
      fibre areas of 5,153 +/- 273 and 4,828 +/- 312 microns 2 respectively, which did
      not differ from the controls (4,482 +/- 306 and 4,699 +/- 310 microns 2).
      Percentages of type I fibres were similar in the two groups (47.2 +/- 2.5% in GH
      deficiency and 45.3 +/- 2.2% in controls). No difference in the variability of
      type I or II fibre areas was demonstrated between the groups. Correlations
      between the relative contribution to total fibre area by type I fibres (mean
      fibre area x percent) and maximal oxygen uptake (p = 0.006), and between type II
      fibres and quadriceps force (p = 0.035) were noted in GH-deficient adults before
      treatment. Following rhGH treatment, no change was noted in mean fibre areas,
      variability of fibre areas, or percentage of either fibre type.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1398471
TI  - Evaluation of GH paradoxical responses to TRH and LHRH in acromegalic patients
      during long-term treatment with octreotide.
AB  - In some acromegalics, GH release can be induced by TRH and/or LHRH
      administration. The pathogenesis of these GH paradoxical responses was supposed
      to be a somatotroph-reduced sensitivity to somatostatin, somatotrophin release
      inhibiting factor (SRIF), or an hypothalamic derangement of the SRIF release. In
      this study, this hypothesis was investigated by means of GH suppression during
      chronic therapy with octreotide [Somatostatin analogue (SMS)] in order to
      evaluate the possible correlation between GH and insulin-like growth factor 1
      (IGF-1) normalization and the disappearance of these paradoxical responses in 15
      acromegalic patients: 15/15 with a paradoxical GH rise after TRH and 7/15 with a
      paradoxical GH rise after LHRH. SMS therapy was administered subcutaneously at
      the dose of 150-450 micrograms/day. During the treatment, GH and IGF-1 levels
      normalized in 12 patients and were reduced in the remaining 3 others. The GH
      response to TRH disappeared in 7 patients, while the GH response to LHRH
      disappeared in 4 patients. chi 2 analysis failed to show any significant
      correlation between GH and IGF-1 normalization and the disappearance of GH
      response to TRH and LHRH (chi 2 = 0.00686). No linear correlation existed between
      GH/IGF-1 decrease and GH peak or area under the curve at any time ('r' values:
      TRH test, GH -0.47, IGF-1 -0.48; LHRH test, GH -0.50, IGF-1 -0.49). The absence
      of any significant correlation between GH/IGF-1 normalization and the
      disappearance of GH paradoxical responses during chronic octreotide
      administration suggests that other factors apart from SRIF sensitivity are
      involved in the genesis of these responses.

PMID- 1398473
TI  - Serum osteocalcin levels do not change during rapidly induced hypercalcemia in
      healthy subjects.
AB  - Since osteocalcin has been suggested to play a role in calcium homeostasis, we
      investigated its serum levels in 6 healthy subjects during a rapid calcium
      infusion. Serum levels of intact parathyroid hormone (PTH), 25-hydroxyvitamin D
      [25-(OH) D3] and 1,25-dihydroxyvitamin D [1,25-(OH)2 D3] were also determined.
      The calcium infusion increased plasma-ionized calcium levels from 1.25 +/- 0.04
      to 1.54 +/- 0.07 mmol/l at 30 min (p less than 0.05). Concomitantly, serum levels
      of intact PTH declined from 2.1 +/- 0.9 to 0.2 +/- 0.3 mmol/l (p less than 0.05).
      In contrast, serum osteocalcin levels did not change. Further, during calcium
      infusion, serum levels of 1,25-(OH)2 D3 decreased from 81 +/- 17 to 75 +/- 15
      pmol/l (p less than 0.05) whereas serum levels of 25-(OH) D3 did not change. The
      results therefore suggest that calcium per se does not influence osteocalcin
      secretion.

PMID- 1398474
TI  - Mechanisms of vasopressin secretion.
AB  - The magnocellular vasopressin system of the rat has been studied intensively in
      recent years. This review outlines the electrophysiological characteristics of
      vasopressin neurons, the characteristics of stimulus-secretion coupling in the
      neural lobe, and describes some of the major features of the neural regulation of
      this system which underlie physiological regulation of vasopressin release by
      osmoregulatory stimuli. The major afferent pathways to the magnocellular system
      are now well characterised. Those involved in osmoregulation have been mapped
      using expression of the primary response gene c-fos as a marker for neuronal
      activation.

PMID- 1398475
TI  - Effect of growth hormone on liver glycogen accumulation in suckling rats.
AB  - The regulation of liver glycogen turnover in the neonatal period differs from
      that of the adult state. Little is also known about the regulation exerted by GH
      in the first period of life. To shed light on the regulation of glycogen
      production and in particular to study the role of GH on liver glycogen
      accumulation, we investigated the effect of GH administration in control or GH
      deficient neonatal rats. A slow-release GH preparation was injected
      subcutaneously on days 9 and 12 of life, in normal and neonatally treated rats
      with thyroxine or cortisol. Seventy-two hours after the last GH administration,
      liver glycogen was increased without concomitant elevation of plasma insulin and
      corticosterone levels and in addition without sequential inactivation of glycogen
      synthase. These data strongly suggest that the current concepts on the regulation
      of the hepatic synthesis of glycogen should be revised.

PMID- 1398476
TI  - Smoking effects on the hormonal balance of fertile women.
AB  - We evaluated serum pituitary hormones (prolactin, follicle-stimulating hormone,
      luteinizing hormone), gonadal hormones (estrone, estradiol, progesterone), sex
      steroid binding protein (SBP) and urine estrogens in 684 healthy fertile women,
      subdivided into smokers (n = 237) and nonsmokers (n = 447). The aim of the work
      was to elucidate whether smoking habits can affect hormonal balance. Smoking
      interference of estrogen metabolism has been postulated, but no unequivocal data
      have been reported. A protective role against breast cancer has even been
      suggested on the basis of a reduced estrogenic activity found in smokers. Our
      data showed a considerable interference of smoking on PRL secretion, probably
      related to a direct inhibiting activity of nicotine. Estrogen catabolism could
      also be involved, and a catabolic shift of 16 alpha-hydroxylation in favour of 2
      alpha-hydroxylated catabolites, via the hepatic cytochrome P-450 system could be
      hypothesized.

PMID- 1398477
TI  - Adrenal- and ovarian-vein steroids and LH response to GnRH in two patients with
      virilizing adrenocortical adenoma studied by selective catheterizations.
AB  - Two women with androgen-secreting adrenal adenomas were studied by selective
      adrenal- and ovarian-vein catheterization. Blood samples were collected for
      determination of testosterone, androstenedione, dehydroepiandrosterone sulfate
      and cortisol. In a preoperative stimulation test with gonadotropin-releasing
      hormone, the response of luteinizing hormone was enhanced in both subjects. In
      catheterization studies, the venous gradients for the hormones were not
      diagnostic for the source of hyperandrogenism in either of the patients.

PMID- 1398478
TI  - Calcinosis and metastatic calcification due to vitamin D intoxication. A case
      report and review.
AB  - Vitamin D, a fat-soluble vitamin, can be associated with significant morbidity
      when prescribed in large doses. We describe a hypoparathyroid patient with
      vitamin D intoxication who developed painful periarticular calcinosis,
      nephrocalcinosis with hypertension and chronic renal failure in addition to band
      keratopathy and hearing loss. He was treated with combination therapy including
      prednisone, phosphate-binding antacid, phenytoin and disodium etidronate. After
      20 months of follow-up there was a significant reduction of periarticular
      calcinosis, but no improvement in renal function, band keratopathy or hearing
      loss and possible calcification of the ossicles. The clinicopathologic features
      of metastatic calcification and the various treatment modalities are reviewed.

PMID- 1398479
TI  - Autoimmune insulin syndrome in a patient with progressive systemic sclerosis
      receiving penicillamine.
AB  - The case of a patient with progressive systemic sclerosis, who developed
      hypoglycaemia and insulin autoantibodies, is described. Repeated blood glucose
      measurements showed levels less than 2.8 mmol/l. High immunoreactive insulin
      levels, with undetectable free insulin, led to the discovery of anti-insulin
      antibodies in the patient's serum. He had no history of exogenous insulin use and
      was receiving penicillamine treatment. A double mechanism for the autoimmune
      insulin syndrome in this case is proposed: acting in a patient with increased
      humoral immunoresponsiveness, penicillamine might have induced the development of
      insulin autoantibodies.

PMID- 1398481
TI  - Vitamin E dietary supplementation protects against carbon tetrachloride-induced
      chronic liver damage and cirrhosis.
AB  - Previous studies have shown that alpha-tocopherol (vitamin E) pretreatment of
      experimental animals can protect against acute liver necrosis induced by carbon
      tetrachloride. In this study we investigated whether the increase of vitamin E
      liver content by dietary supplementation influences chronic liver damage and
      cirrhosis induced by carbon tetrachloride in the rat. Our data indicate that
      vitamin E supplementation did not interfere with the growth rate of the animals
      and increased about threefold the liver's content of the vitamin. Vitamin E
      supplementation significantly reduced oxidative liver damage, but it was not
      effective in protecting against development of fatty liver and did not interfere
      with metabolic activation of carbon tetrachloride. Moreover, vitamin E-fed
      animals showed incomplete but significant prevention of liver necrosis and
      cirrhosis induced by carbon tetrachloride. This has been shown by means of
      histological examination, analysis of serum parameters and biochemical evaluation
      of collagen content. These results show that an increased liver content of
      vitamin E can afford a significant degree of protection against carbon
      tetrachloride-induced chronic liver damage and cirrhosis.

PMID- 1398482
TI  - S-adenosylmethionine treatment prevents carbon tetrachloride-induced S
      adenosylmethionine synthetase inactivation and attenuates liver injury.
AB  - Administration of carbon tetrachloride to rats resulted in induction of hepatic
      fibrosis and a 60% reduction of hepatic S-adenosylmethionine synthetase activity
      without producing any significant modification of hepatic levels of S
      adenosylmethionine synthetase messenger RNA. The reduction of S
      adenosylmethionine synthetase activity was corrected by treatment with S
      adenosylmethionine (3 mg/kg/day, intramuscularly). Administration of carbon
      tetrachloride also produced a 45% depletion of liver glutathione (reduced form)
      that was corrected by S-adenosylmethionine treatment. After the rats received
      carbon tetrachloride, a 2.3-fold increase in liver collagen was observed; prolyl
      hydroxylase activity was 2.5 times greater than that seen in controls. These
      increases were attenuated in animals treated with carbon tetrachloride and S
      adenosylmethionine. The attenuation by S-adenosylmethionine treatment of the
      fibrogenic effect of carbon tetrachloride was associated with a decrease in the
      number of rats in which cirrhosis developed.

PMID- 1398480
TI  - Ethanol-induced vasoconstriction causes focal hepatocellular injury in the
      isolated perfused rat liver.
AB  - The role of microcirculation in the pathogenesis of alcoholic liver injury was
      investigated in isolated perfused livers from fed rats. Infusion of ethanol into
      the portal vein at concentrations ranging from 25 to 200 mmol/L increased portal
      pressure, which is an indicator of hepatic vasoconstriction, in a concentration
      dependent fashion. Portal pressure started to rise immediately on initiation of
      ethanol load and remained at higher than basal levels throughout the period of
      ethanol infusion. Release of lactate dehydrogenase, an indicator of cell injury,
      into the effluent perfusate began to increase after 20 to 30 min of ethanol
      infusion and continued to increase until the end of the experiment (60 min after
      the initiation of ethanol infusion). The lactate dehydrogenase level in the
      effluent perfusate at 60 min was dependent on the ethanol concentration (0
      mmol/L, 8 +/- 3 IU/L; 25 mmol/L, 22 +/- 3 IU/L; 50 mmol/L, 51 +/- 11 IU/L; 100
      mmol/L, 60 +/- 7 IU/L; 200 mmol/L, 120 +/- 7 IU/L). Simultaneous infusion of
      sodium nitroprusside (100 mumol/L), a known vasodilator, inhibited significantly
      the ethanol-induced increases in portal pressure and lactate dehydrogenase
      release by abolishing hepatic vasoconstriction. In histological examinations
      focal hepatocellular necrosis, evidenced by trypan blue staining of cell nuclei,
      was detected predominantly in midzonal and pericentral areas of the liver lobule
      after 60 min of ethanol infusion. Change in portal pressure during 60 min of
      ethanol infusion correlated significantly with levels of lactate dehydrogenase
      after ethanol infusion (r = 0.82; p less than 0.001).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1398483
TI  - Papaverine inhibits transcytotic vesicle transport and lipid excretion into bile
      in isolated perfused rat liver.
AB  - Papaverine is a nonspecific smooth muscle relaxant and a phosphodiesterase
      inhibitor. Its effects on biliary excretion of lipids and horseradish peroxidase
      were investigated in a single-pass isolated perfused rat liver model. A constant
      infusion of papaverine (1.6 mumol/min; 40 mumol/L) significantly increased bile
      flow (microliters per minute per gram of liver) before (2.03 +/- 0.09 vs. 1.0 +/-
      0.06) and after sodium taurocholate infusion (2.77 +/- 0.10 vs. 1.88 +/- 0.11).
      However, papaverine significantly and reversibly reduced biliary excretion of
      phospholipids and cholesterol (nanomoles per minute per gram of liver) after a
      1.0 mumol/min sodium taurocholate infusion, from 7.45 +/- 0.83 and 1.42 +/- 0.15
      to 1.75 +/- 0.18 and 0.39 +/- 0.06, respectively (p less than 0.01), whereas
      secretion of bile acids was unaffected. When a 1-min pulse of horseradish
      peroxidase (25 mg) was infused in isolated perfused rat liver after a continuous
      infusion of N6,O-2'-dibutyryladenosine 3',5'-cyclic monophosphate (0.25
      mumol/min; 6.25 mumol/L), horseradish peroxidase appeared in bile in an early (4
      to 6 min) and late (20 to 25 min) peak. Papaverine significantly reduced the late
      peak, from 1.211 +/- 0.264 to 0.498 +/- 0.107 (p less than 0.01). Papaverine had
      no significant effects on either cyclic AMP or cyclic GMP in the liver and bile,
      although it has been reported that papaverine is a phosphodiesterase inhibitor.
      These findings indicate that papaverine inhibits biliary excretion of lipids but
      not bile acids, and they suggest that papaverine has an inhibitory effect on
      transcytotic vesicle transport independent of an increase of cyclic nucleotides
      in hepatocytes.

PMID- 1398484
TI  - The role of nitric oxide in the vascular hyporesponsiveness to methoxamine in
      portal hypertensive rats.
AB  - This study examined whether an increased activity of the endothelium-derived
      relaxing factor, nitric oxide, may account for the hyporesponsiveness to
      vasoconstrictors in portal hypertension. We performed dose-response curves to
      methoxamine, an alpha-adrenoceptor agonist, with and without N omega-nitro-L
      arginine, a specific inhibitor of nitric oxide synthesis, in experimental portal
      hypertension. Partial portal vein-ligated or sham-operated rats were pretreated
      with a continuous intravenous infusion of either N omega-nitro-L-arginine (50
      micrograms.kg-1.min-1) or saline. Thirty minutes after starting the infusion of N
      omega-nitro-L-arginine or saline an infusion of methoxamine (10, 30 and 100
      micrograms.kg-1.min-1) was added. Total peripheral resistance was calculated from
      mean arterial pressure and cardiac index. Repeated measurements of cardiac index
      were performed by a thermodilution technique. In portal vein-ligated rats
      pretreated with saline, the increase in total peripheral resistance after
      methoxamine infusion was significantly less than that of sham-operated rats (0.2
      +/- 0.1 vs. 1.0 +/- 0.3, 0.6 +/- 0.1 vs. 1.6 +/- 0.3 and 3.7 +/- 0.5 vs. 6.1 +/-
      0.7 mm Hg.ml-1.min.100 gm, p less than 0.05, methoxamine 10, 30 and 100
      micrograms.kg-1.min-1, respectively). In the presence of N omega-nitro-L
      arginine, the change in total peripheral resistance after methoxamine infusion
      was similar in both groups (p greater than 0.05). In conclusion, this study
      demonstrates that a vascular hyporesponsiveness to methoxamine is present in
      portal vein-ligated rats and that this hyporesponsiveness is reversed by blockade
      of nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398485
TI  - The perfused liver is capable of producing all transferrin glycan variants found
      in the sera of intact rats.
AB  - The single oligosaccharide attachment in rat transferrin exhibits marked
      structural microheterogeneity. In this study we examined whether all
      microheterogeneous forms of rat transferrin found in plasma are derived from a
      single organ, such as the liver. To this end we analyzed the glycans of rat
      transferrin synthesized by the isolated perfused rat liver by a method
      established earlier for rat transferrin isolated from rat plasma. Our
      observations provide evidence that the liver can and does produce all variant rat
      transferrin glycans present in plasma. However, this discovery does not preclude
      the possibility that extrahepatic sources with an active rat transferrin gene may
      contribute to the circulation rat transferrin molecules, which bear glycan
      variants identical to those made by the liver. The glycan spectra of rat
      transferrin in plasma and in liver perfusate compared closely with each other in
      a quantitative sense. Nevertheless, rat transferrin in the perfusate was
      sialylated to a lesser extent and fucosylated to a greater extent than rat
      transferrin in plasma. These differences could not be eliminated by
      supplementation of the medium with insulin, dexamethasone, pyruvate and adenine
      or adenosine either alone or in combinations, nor could it be eliminated by use
      of a fluorocarbon O2 carrier. In contrast, epidermal growth factor normalized
      both parameters. The pH of the perfusing medium also influenced sialylation and
      fucosylation in such a way that higher pH brought these parameters closer to
      their values in plasma rat transferrin. Lower pH, on the other hand, reduced
      sialylation and left the fucosylation index unchanged.

PMID- 1398486
TI  - Regenerative stimulus increases hepatocyte tight junctional permeability.
AB  - Experience with young animals, animals administered certain hepatotoxins and
      animals with two-thirds hepatectomy suggests that tight junctional permeability
      is increased in states characterized by architectural remodeling in the liver. In
      this work we correlate changes in tight junctional morphometry induced by two
      thirds hepatectomy with changes in biliary permeability assessed by sucrose and
      horseradish peroxidase permeation and by alterations in biliary outputs of
      anionic and cationic cholephilic probes. By freeze-fracture examination tight
      junctional strand counts, density and orientation parallel to canaliculi were all
      reduced 24 hr after two-thirds hepatectomy. Occasionally, strands were
      perpendicular to the canaliculi, creating an unobstructed communication between
      bile and intercellular spaces. These morphological changes correlated with
      increased sucrose and paracellular horseradish peroxidase access into bile, with
      reduced biliary outputs of low molecular weight and especially with cationic
      cholephilic probes. The data support an increased but still charge-selective
      permeability of the biliary tree, which was induced by two-thirds hepatectomy 24
      hr before. Presumably, fixed intercellular connections (tight junctions and gap
      junctions) must be loosened or lysed to allow the architectural reorganization
      required by the hepatocellular regenerative process.

PMID- 1398487
TI  - Congenital diseases of intrahepatic bile ducts: variations on the theme "ductal
      plate malformation".

PMID- 1398488
TI  - Guidelines for training in hepatology.

PMID- 1398489
TI  - The making of a hepatologist.

PMID- 1398490
TI  - Nitric oxide: the elusive mediator of the hyperdynamic circulation of cirrhosis?

PMID- 1398491
TI  - Nitric oxide and hyperdynamic circulation in portal hypertension.

PMID- 1398492
TI  - The p53 "knockout": gone but not forgotten.

PMID- 1398493
TI  - Hepatology elsewhere: twenty years after!

PMID- 1398494
TI  - A pilot study of 2',3'-dideoxyinosine for the treatment of chronic hepatitis B.
AB  - The nucleoside analog 2',3'-dideoxyinosine, currently being used to treat
      patients infected with the human immunodeficiency virus, has been shown to
      inhibit viral replication in certain cell culture systems of hepatitis B virus
      and the duck model of chronic hepatitis B infection. We studied the effect of
      dideoxyinosine on viral replication in patients with chronic hepatitis B. In the
      initial dose-finding phase, patients received sequential 2-wk courses of
      dideoxyinosine in escalating doses of 3, 6 and 9 mg/kg/day. In the second, long
      term treatment phase, patients received dideoxyinosine at a dose of 9 mg/kg/day
      for 12 wk. Dideoxyinosine was given orally in three divided doses. The effects of
      dideoxyinosine on hepatitis B were assessed by serial measurements of ALT,
      hepatitis B virus DNA and DNA polymerase activity in serum. Six patients
      completed the dose-finding phase, and five patients continued into the long-term
      treatment phase. No significant differences were seen in serum aminotransferases,
      hepatitis B virus DNA levels or DNA polymerase activity at any time during
      treatment when compared with pretreatment levels. All patients remained positive
      for HBeAg during treatment and during 6 mo of follow-up. Thus at the doses
      tested, dideoxyinosine had no appreciable effect on viral replication in patients
      with chronic hepatitis B.

PMID- 1398495
TI  - Characterization of the liver cytosol antigen type 1 reacting with autoantibodies
      in chronic active hepatitis.
AB  - An autoantibody to liver cytosol was previously described in childhood autoimmune
      chronic active hepatitis type 2. The antigen, liver cytosol antigen type 1, was
      for the first time partially purified using gel filtration and ion exchange
      chromatography, and it was characterized using immunodiffusion, immunoblot and
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the
      immunoprecipitate. Immunoblot detected a unique antigenic peptide at 62 kD from
      human cytosol and at 58 kD from rat cytosol. The same peptides were also detected
      when immunoprecipitates of liver cytosol antigen type 1 and autoantibodies to
      liver cytosol antigen were submitted to sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. A polymeric structure, probably a tetramer, is suggested for
      native liver cytosol antigen type 1 because in gel filtration chromatography
      liver cytosol antigen type 1 was eluted as a protein of a molecular weight
      between 240 and 290 kD when human liver cytosol was fractionated and between 220
      and 270 kD from rat liver cytosol. Liver cytosol antigen type 1 is probably poor
      in carbohydrates because it was not stained by periodic acid-Schiff stain. The
      autoantibodies to liver cytosol were frequently found in association with
      antiliver kidney microsomal autoantibodies type 1, which are directed against the
      cytochrome P-450 of the IID6 subfamily. Antiliver kidney microsomal
      autoantibodies type 1 but not antiliver cytosol autoantibodies were found in
      association with antibodies to hepatitis C virus. Autoantibodies to liver cytosol
      antigen type 1 seem to be a more specific marker for autoimmune hepatitis type 2
      than antiliver kidney microsomal antibodies type 1 autoantibodies.

PMID- 1398496
TI  - Antimitochondrial antibodies in kindreds of patients with primary biliary
      cirrhosis: antimitochondrial antibodies are unique to clinical disease and are
      absent in asymptomatic family members.
AB  - The 2-oxo-acid dehydrogenase family of enzymes have been identified as the major
      mitochondrial autoantigens of primary biliary cirrhosis. Using immunoblotting,
      enzyme-linked immunosorbent assay and enzyme inhibition with both purified
      mitochondrial proteins and recombinant autoantigens, we have studied family
      members and spouses of patients with primary biliary cirrhosis for the presence
      of antimitochondrial antibodies. Antimitochondrial antibodies and other common
      autoantigens were also tested for by indirect immunofluorescence. This study
      included 27 index patients with primary biliary cirrhosis, 15 spouses and 48
      first- and second-degree relatives. Overall, 7 relatives (11%) were positive for
      autoantibodies to nuclear and cytoplasmic antigens by indirect immunofluorescence
      against mouse liver and stomach sections. However, with immunofluorescence, the
      reactivity strictly paralleled that of antimitochondrial antibodies in only one
      of these (1:640)--a sibling with mild pruritus and a liver biopsy specimen
      diagnostic of primary biliary cirrhosis despite normal levels of serum alkaline
      phosphatase. In addition, one of the mothers, who had a history of sarcoidosis,
      was positive by immunoblotting for antibodies to the E2 subunit of the pyruvate
      dehydrogenase complex and protein X. All other relatives were negative for all of
      the assays. Antibodies to neither the 2-oxo-acid dehydrogenase enzymes nor the
      recently proposed family of naturally occurring mitochondrial antibodies were
      found in spouses or healthy relatives. Three other first-degree relatives
      suffered from liver disease: two died (one from primary biliary cirrhosis and the
      other from an unknown type of liver disease) and one (a sibling with primary
      biliary cirrhosis) was unavailable for testing. Our results are consistent with a
      familial predisposition to primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1398497
TI  - Does elective sclerotherapy improve the efficacy of long-term propranolol for
      prevention of recurrent bleeding in patients with severe cirrhosis? A prospective
      multicenter, randomized trial.
AB  - We conducted a prospective, multicenter, randomized trial to compare the efficacy
      of sclerotherapy plus propranolol with that of propranolol alone in the
      prevention of recurrent gastroesophageal bleeding in severely cirrhotic patients.
      For 2 yr (1987 to 1988) 131 patients (96% of whom were alcoholic) with Child-Pugh
      class B or C cirrhosis (56% were class B and 44% were class C) were randomly
      assigned to one of our two treatment groups after cessation of variceal bleeding,
      without hemostatic sclerosis, and were observed for at least 2 yr. Treatment
      observance was good in 89% of cases; alcohol withdrawal was observed in 62% of
      cases. Sclerotherapy was performed weekly with 1% polidocanol, and variceal
      obliteration was obtained in 83% of cases, in a mean number of four sessions. The
      cumulative percentages (expressed as mean +/- S.D.) of recurrent bleeding at 2 yr
      were 42% +/- 6% for propranolol plus sclerotherapy and 59% +/- 6% for propranolol
      alone (a nonsignificant difference). Twenty-eight patients from the propranolol
      group but only 12 patients from the propranolol-plus-sclerotherapy group had
      recurrent bleeding from esophageal variceal rupture (p less than 0.01). The total
      number of blood units per patient with recurrent bleeding was slightly but not
      significantly more important in the propranolol group (8 +/- 7) than in the
      propranolol-plus-sclerotherapy group (5 +/- 5; p = 0.09).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1398498
TI  - Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease: a dose
      response study.
AB  - Previous studies from our groups have demonstrated improvements in biochemical
      markers of liver function when cystic fibrosis patients with associated liver
      disease were administered oral ursodeoxycholic acid. The magnitude of the
      response was somewhat less than that found when comparable doses (10 to 15 mg/kg
      body wt/day) of ursodeoxycholic acid are given to other liver disease patients;
      this may be explained by the bile acid malabsorption that is characteristic of
      the disease. For this reason a dose-response study was carried out in nine cystic
      fibrosis patients with liver disease to establish whether improved efficacy could
      be obtained with higher doses. Ursodeoxycholic acid in doses of 5, 10 and 15
      mg/kg body wt/day was given orally for consecutive 2-mo periods in a replicated
      Latin-square design. After this, all patients received 20 mg/kg body wt/day.
      Liver function, individual serum bile acids and biliary bile acid composition
      were determined at entry and at the end of each treatment period. Our data
      demonstrate that the magnitude of the biochemical improvement in serum liver
      enzymes was significantly greater with higher doses of ursodeoxycholic acid; at
      20 mg/kg body wt/day it was similar to that reported for patients with other
      liver diseases administered lower doses. Biliary ursodeoxycholic acid enrichment
      increased with increasing doses, attaining 42% +/- 6% of the total biliary bile
      acids with the highest dose. Fasting serum ursodeoxycholic acid concentrations
      increased during ursodeoxycholic acid administration but were variable and
      correlated poorly with the dose of ursodeoxycholic acid administered, whereas no
      correlation was found between serum ursodeoxycholic acid concentration and the
      proportion of ursodeoxycholic acid in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398499
TI  - Deficient interleukin-2 responsiveness of T lymphocytes from patients with
      primary biliary cirrhosis.
AB  - There is increasing evidence that primary biliary cirrhosis is associated with an
      alteration of the immune system. Although the cause remains unknown, it has been
      suggested that the immune system of patients with primary biliary cirrhosis is
      involved in the pathogenesis of their disease. We have investigated the T-cell
      function in patients with primary biliary cirrhosis and have found defective
      phytohemagglutinin-induced T-cell mitogenesis. Likewise, their blastogenic
      response to CD3 monoclonal antibody was also depressed, although the DNA
      synthesis induced by stimulation with phorbol esters (12-O-tetradecanoil-phorbol
      13-acetate) plus ionophore (ionomycin) was normal. These alterations could not be
      ascribed either to a decreased synthesis of interleukin-2 or to a defective
      expression of interleukin-2 receptor after cellular activation. Moreover, this
      defective proliferative response of T lymphocytes was observed even in the
      presence of saturating concentrations of exogenous interleukin-2. These results
      represent evidence of the deficiency in the interleukin-2-dependent pathway found
      in T lymphocytes from patients with primary biliary cirrhosis.

PMID- 1398500
TI  - Effect of loxiglumide and atropine on erythromycin-induced reduction in
      gallbladder volume in human subjects.
AB  - This study was undertaken to investigate the effect of erythromycin, a motilin
      agonist with prokinetic activity, on fasting gallbladder volume. To evaluate the
      mechanism of action of erythromycin on gallbladder motility, erythromycin (3.5
      mg/kg.20 min, intravenously) was infused on three separate occasions: during
      cholinergic blockage with atropine (0.005 mg/kg.hr), during cholecystokinin
      receptor blockade with loxiglumide (10 mg/kg.hr) and during saline solution
      infusion (control). Atropine, loxiglumide and saline solution infusions were
      started 3 hr before administration of erythromycin and were continued for 3 hr
      thereafter. Gallbladder volumes (measured by ultrasonography), plasma
      cholecystokinin levels (radioimmunoassay) and plasma pancreatic polypeptide
      levels (radioimmunoassay) were determined at regular intervals for 6 hr in six
      healthy volunteers. During the 3-hr infusion before administration of
      erythromycin, both loxiglumide and atropine significantly increased gallbladder
      volumes--from 18 +/- 2 to 37 +/- 3 cm3 (p less than 0.05) and from 17 +/- 3 to 24
      +/- 2 cm3 (p less than 0.05), respectively--whereas saline solution did not
      significantly affect gallbladder volume. During control saline solution infusion,
      erythromycin induced prolonged gallbladder contraction that was significant (p
      less than 0.05) between 60 and 180 min and reached a maximum of 45% +/- 8% at 150
      min. Plasma cholecystokinin levels were not affected by erythromycin.
      Erythromycin induced a significant (p less than 0.05) increase in plasma
      pancreatic polypeptide levels, from 12 +/- 1 pmol/L to 34 +/- 3 pmol/L.
      Loxiglumide did not prevent the erythromycin-induced reduction in gallbladder
      volume. Atropine markedly reduced the effect of erythromycin, causing slight but
      significant (p less than 0.05) gallbladder volume reductions (18% +/- 4%) between
      150 and 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398501
TI  - 31P magnetic resonance spectroscopy detects a functional abnormality in liver
      metabolism after acetaminophen poisoning.
AB  - Eighteen patients with acetaminophen poisoning were studied with 31P magnetic
      resonance spectroscopy to measure phosphorus-containing metabolites in their
      livers. The concentrations of all magnetic resonance-detectable metabolites fell
      in parallel with a decrease in the synthetic ability of the liver, indicated by
      the prothrombin time ratio (international normalized ratio). In particular, ATP
      fell to about 20% of its normal concentration in severely affected patients, as
      did the phosphodiester signal, which is thought to arise mainly from the
      endoplasmic reticulum in the liver. The correlation between ATP levels and
      international normalized ratio suggests that the international normalized ratio
      is a more accurate measure of the number of viable hepatocytes than are other
      biochemical tests.

PMID- 1398502
TI  - Saturability of hepatic iron deposits in genetic hemochromatosis.
AB  - The relationship of pretreatment serum ferritin and hepatic iron concentration to
      body iron removed by venesections was evaluated in 33 patients with genetic
      hemochromatosis. The median values of the three variables considered were 1,950
      micrograms/L (range = 255 to 10,000), 1,175 micrograms/100 mg dry weight (range =
      270 to 4,310) and 10 gm (range = 2 to 41), respectively. At basal liver biopsy 18
      patients had cirrhosis, 6 patients had fibrosis and 9 patients had a normal
      pattern; siderosis was degree 3 in 6 patients and degree 4 in 27 patients. The
      results of fitting a polynomial regression of second degree showed that the curve
      of serum ferritin on iron removed was a straight line (R2 = 0.79, with a
      significant coefficient of linearity, p less than 0.01, and a nonsignificant
      coefficient of curvature), whereas that of hepatic iron concentration on iron
      removed showed a curvature (R2 = 0.62, with significant coefficient of linearity
      and curvature, p less than 0.01) and reached a plateau. The sigmoid model fit the
      curve of hepatic iron concentration on iron removed (R2 = 0.61), which suggested
      a saturation of hepatic iron storage capability; the asymptote corresponded to a
      hepatic iron concentration of about 2,000 micrograms/100 mg. In alcoholic
      patients (17 cases) the location of the sigmoid was greater than in nonalcoholic
      patients. Our results suggest that iron deposition occurs in the liver before
      other organs are involved and that with massive iron overload hepatic deposits
      reach saturation, after which hepatic iron concentration does not always reflect
      the amount of total stores. Alcohol consumption could slow the saturation of
      hepatic iron deposits.

PMID- 1398503
TI  - Dietary N-3 polyunsaturated fatty acids decrease biliary cholesterol saturation
      in gallstone disease.
AB  - Because fatty acid composition of biliary phospholipids influences cholesterol
      secretion into bile, we investigated whether replacement of n-1 monounsaturated
      or n-6 polyunsaturated fatty acids with n-3 polyunsaturated fatty acids in
      biliary phosphatidylcholines reduces supersaturation with cholesterol and
      prevents precipitation of cholesterol crystals in bile of gallstone patients.
      Seven patients with radiolucent gallstones in functioning gallbladders were
      studied before (control) and after 5 wk of dietary supplementation with marine
      fish oil (11.3 gm/day = 3.75 gm n-3 polyunsaturated fatty acids/day). Duodenal
      bile was collected for analysis during intravenous infusion of cholecystokinin.
      Gallbladder emptying in response to cholecystokinin was comparable before and
      during intake of n-3 polyunsaturated fatty acids. Intake of n-3 polyunsaturated
      fatty acids increased (p less than 0.001) the fractions of eicosapentaenoic and
      docosahexaenoic acids and decreased the fractions of linoleic (p less than 0.001)
      and arachidonic acids (p less than 0.02) in biliary phospholipids. Concomitantly,
      the molar ratio of cholesterol to phospholipids decreased (-19%; p less than
      0.05). As a consequence, the cholesterol saturation index was reduced by -25% (p
      = 0.01), from 1.60 +/- 0.44 to 1.24 +/- 0.38. However, in vitro nucleation time
      of duodenal bile was not prolonged. The decrease in cholesterol saturation was
      not sufficient to prevent nucleation of cholesterol crystals in bile of gallstone
      patients. In conclusion, our data suggest that cholesterol saturation can be
      influenced by the fatty acid composition of the phosphatidylcholines secreted in
      bile.

PMID- 1398504
TI  - Analysis of hepatocellular proliferation: study of archival liver tissue is
      facilitated by an endogenous marker of DNA replication.
AB  - Assessment of liver regeneration with endogenous genes that are expressed during
      DNA replication is physiological, specific and direct. To determine whether H3
      histone messenger RNA expression (which is tightly coupled with DNA synthesis)
      could be used for this purpose, we initially examined liver regeneration in a
      mouse model. After partial hepatectomy, RNA transblot studies showed induction of
      H3 histone messenger RNA expression in regenerating mouse livers. In situ
      molecular hybridization demonstrated that the overall pattern of H3 histone
      messenger RNA expression correlated with [3H]thymidine labeling of hepatocytes.
      After partial hepatectomy, H3 histone messenger RNA expression in hepatocytes
      peaked at 48 hr (greater than 60 times greater than at 24 hr; p less than 0.001)
      and then rapidly declined. Although hepatocyte labeling with [3H]thymidine showed
      similar kinetics of liver regeneration, use of this parameter resulted in
      overestimation of the proliferative compartment when it was compared with H3
      histone messenger RNA expression. Next we determined whether H3 histone messenger
      RNA expression could be used to study hepatocellular proliferation in archival
      human material. H3 histone messenger RNA-expressing hepatocytes were identified
      on in situ hybridization in patients with acute or chronic active hepatitis and
      active cirrhosis, but not inactive cirrhosis. These studies demonstrate that H3
      histone messenger RNA is expressed in a phasic manner during liver regeneration.
      Use of H3 histone messenger RNA expression to evaluate hepatocellular
      proliferation should facilitate clinical studies and greatly advance our
      understanding of the pathophysiology of liver regeneration.

PMID- 1398505
TI  - Metabolic clearance rate of arginine vasopressin in patients with cirrhosis.
AB  - Metabolic clearance rate and half-time of arginine vasopressin were measured in
      43 cirrhotic patients and 10 control subjects. Synthetic arginine vasopressin was
      infused intravenously at a rate of 500 pg/min/kg of body weight for 75 min. The
      metabolic clearance rate was significantly reduced, and the half-time of arginine
      vasopressin after stopping the infusion was significantly increased in patients
      with cirrhosis, particularly in those with ascites and in those with moderate or
      severe liver dysfunction. Changes in metabolic clearance rate and half-time of
      arginine vasopressin correlated with the score of the liver dysfunction,
      prothrombin activity and levels of serum albumin and bilirubin but not with
      parameters of kidney function (serum creatinine levels and clearance of
      creatinine). We conclude that reduced metabolic clearance rate and prolonged half
      time of vasopressin in plasma are frequent findings in cirrhotic patients with
      poor liver function. This impaired catabolism of antidiuretic hormone may
      contribute to maintaining elevated plasma levels of this hormone in these
      patients and may be an additional factor leading to fluid retention and to
      dilutional hyponatremia.

PMID- 1398506
TI  - Acute effects of topical methyl tert-butyl ether or ethyl propionate on
      gallbladder histology in animals: a comparison of two solvents for contact
      dissolution of cholesterol gallstones.
AB  - Experiments were performed in anesthetized rabbits and piglets to assess
      gallbladder mucosal injury during irrigation with methyl tert-butyl ether, a C5
      ether, or ethyl propionate, a C5 ester--two organic solvents used in the contact
      dissolution of cholesterol gallstones. In 44 New Zealand White rabbits, the
      gallbladder was exposed to individual solvents or saline solution through a
      transhepatic catheter for 2 hr. Gallbladders were then harvested and fixed
      immediately or after a recovery period of 1, 4 or 8 days. Tissue sections were
      examined under light microscopy, and severity of injury was graded with
      predefined criteria by two pathologists blinded to the animals' treatment
      regimens. Histological assessment showed severe mucosal injury such as necrosis
      of the cells at the villus tips immediately after 2 hr of exposure to either
      solvent. After 4 days, injury had decreased significantly; after 8 days, complete
      mucosal healing had taken place. A similar study was performed in 32 piglets.
      Solvent or saline solution was oscillated in and out of the gallbladders of these
      piglets with a computer-controlled syringe pump at a pressure less than the
      leakage pressure of the gallbladder. Histological assessment was performed on
      tissue samples obtained immediately after the procedure or 8 days later. Both
      solvents caused severe mucosal injury; however, after 8 days complete mucosal
      healing had occurred, so that gallbladders exposed to solvent were
      indistinguishable from gallbladders exposed to saline solution, which was used as
      control. We conclude that both methyl tert-butyl ether and ethyl propionate cause
      moderate to severe epithelial injury but that the gallbladder epithelium
      regenerates within a few days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398507
TI  - Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron
      dependent microsomal lipid peroxidation.
AB  - This study investigated the role of cytochrome P-450 2E1 in enhanced microsomal
      lipid peroxidation in experimental alcoholic liver disease. We also examined the
      contribution of this isoform to the increased microsomal injury in alcoholic
      liver disease caused by carbon tetrachloride-induced or iron-induced oxidant
      stress. Adult male Wistar rats were intragastrically infused with a high-fat diet
      and ethanol or glucose for 16 wk; this resulted in hepatic lipid peroxidation and
      fibrogenesis in the ethanol-fed animals. Microsomes were isolated by differential
      centrifugation in the presence of 100 mumol/L deferoxamine, washed twice in
      buffer without deferoxamine and incubated in the absence or presence of ethanol
      (50 mmol/L), carbon tetrachloride (150 mumol/L), ferric citrate (50 mumol/L) or
      ferric citrate plus ethanol at 37 degrees C for 30 min in an NADPH-generating
      system. The basal rate of lipid peroxidation in microsomes isolated from ethanol
      fed rats was increased by 52% compared with that in microsomes from controls.
      Carbon tetrachloride-induced and ferric citrate-induced lipid peroxidation were
      also accentuated in microsomes from ethanol-fed rats, by 76% and 108%,
      respectively. Ethanol added in vitro significantly reduced basal (-58%) and
      ferric citrate-induced (-48%) lipid peroxidation in microsomes from ethanol-fed
      rats, whereas it had an insignificant effect on that in control microsomes. In
      fact, this protective effect of ethanol on microsomes from ethanol-fed rats
      resulted in attenuation of the difference in the level of microsomal lipid
      peroxidation between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398508
TI  - Hepatic accumulation of lysosomes and defective transcytotic vesicular pathways
      in cirrhotic rat liver.
AB  - To investigate the potential role of lysosomes in cirrhosis, we analyzed the
      activity of lysosomal enzymes in rats exposed long-term to phenobarbital and
      carbon tetrachloride. The activity of lysosomal enzymes was markedly increased in
      the homogenate of cirrhotic livers (e.g., arylsulfatase 9 +/- S.D.2 vs. 16 +/- 6
      nmoles.min-1.mg-1 in control rats and cirrhotic rats, respectively; p less than
      0.001). The corresponding plasma levels were also increased (7 +/- 1 vs. 12 +/- 3
      nmoles.min-1.mg-1; p less than 0.01), whereas biliary excretion was diminished
      (16 +/- 7 vs. 7 +/- 2 pmol.min-1.gm liver-1; p less than 0.05) in cirrhotic rats.
      Stereological quantification of lysosomes visualized cytochemically revealed an
      increase of pericanalicular lysosomes averaging 1.5 +/- 0.4 around a canaliculus
      in controls and 3.7 +/- 1.0 in cirrhotic rats (p less than 0.01). Because this
      suggested a defect in the transcellular vesicular pathway, we investigated the
      biliary excretion of horseradish peroxidase and epidermal growth factor in
      perfused livers. Bile flow and total horseradish peroxidase excretion were
      similar in control rats and cirrhotic rats. However, the early peak of biliary
      horseradish peroxidase excretion--usually taken as evidence of paracellular
      transport--was increased in cirrhotic rats (13 +/- 7 vs. 57 +/- 22%; p less than
      0.01), whereas the second peak--reflecting the transcellular vesicular pathway(s)
      -was markedly reduced (87 +/- 7 vs. 43 +/- 22%; p less than 0.001). A similar
      reduction in the biliary excretion of intact epidermal growth factor and of its
      degradation products was found. These results demonstrate an increased number of
      lysosomes in hepatocytes of cirrhotic livers; this appears to be the result of
      accumulation rather than proliferation, in view of the reduced transcellular
      vesicular movement of different markers into bile.

PMID- 1398509
TI  - The prognostic factors for peripheral T-cell lymphomas.
AB  - The peripheral T-cell lymphomas of 50 patients were classified by histological
      type and tumour cell size, the latter as described by the Nebraska Group. There
      was no difference in the pattern of their clinical features among the various
      histological subtypes and their clinical outcome was similar. Cell size and other
      factors including sex, age, presence of B symptoms, sites of primary disease,
      histological subtypes according to the Japanese classification, lactate
      dehydrogenase level and presence of bulky disease did not appear to correlate
      with clinical outcome. However, patients with stage IV disease had significantly
      lower CR rate (9/29 versus 16/21, p = 0.01) and poorer survival at 3 years (p =
      0.05) than those with stage I, II and III disease. Patients receiving COPP, the
      less intensive chemotherapy regimen, appeared to have poorer clinical outcome but
      the difference observed was not statistically significant because of the number
      of patients in each subgroup.

PMID- 1398510
TI  - Angiocentric T-cell lymphoma of the nose, paranasal sinuses and hard palate.
AB  - Sixty-five cases of malignant lymphoma of the nose, paranasal sinuses and hard
      palate were retrospectively analysed to identify the presence or absence of
      angiocentric lesions. We observed that the 23 patients with angiocentric lesions
      had a worse prognosis with a shorter duration of response and also a shorter
      duration of survival, compared with 42 cases of malignant lymphoma of the same
      anatomical region but without angiocentric lesions. Patients with angiocentric
      lymphoma were associated with other bad prognostic factors such as elevated
      levels of lactic dehydrogenase and beta 2 microglobulin, local bone destruction
      and lymphopenia. Immunophenotyping studies showed that most patients with
      angiocentric lesions had T cell lymphomas (18 of 23, 78 per cent). We believe
      that patients with angiocentric T cell lymphomas of the nose, paranasal sinuses
      and hard palate represent a distinctive clinico-pathological entity with
      different clinical presentation and outcome. Patients with angiocentric T cell
      lymphomas had frequent relapse at extranodal sites and combined therapy should be
      considered as the initial therapeutic approach.

PMID- 1398511
TI  - Detection of immunoglobulin gene rearrangement in B-cell lymphomas by polymerase
      chain reaction gene amplification.
AB  - This is a report on our attempt to use polymerase chain reaction (PCR) to detect
      rearrangement of the immunoglobulin gene in the tissue specimens obtained from 30
      patients with non-Hodgkin's lymphomas. There were 20 B-cell lymphomas and 10 T
      cell. All 20 B-cell lymphomas but none of the 10 T-cell lymphomas had JH
      rearrangement by Southern analysis. Two pairs of primers (V670/OL-4 and VH26/OL
      4) were designed to amplify the CDR3 region of the immunoglobulin gene heavy
      chain. The PCR analysis was positive using either one or both pairs of primers in
      11 of the the 20 cases (55 per cent) of B-cell lymphomas which all had positive
      rearrangement by Southern analysis. The two pairs of primers seemed to produce
      complementary results as the specimens may be positive to one pair but negative
      to the other. The false negative rate of 45 per cent is however much higher than
      the respective figures of 18 per cent and 0 per cent observed in our patients
      with acute lymphoblastic leukemia and chronic lymphocytic leukemia in a previous
      study. Peripheral blood and bone marrow biopsy specimens obtained at the time of
      initial diagnosis were available from 10 patients with B-cell lymphomas whose
      lymph node biopsy specimens at the time of diagnosis were positive by both
      Southern analysis and PCR. All these peripheral blood and marrow specimens had no
      microscopic evidence of involvement by lymphoma cells and JH rearrangement was
      not detected by Southern analysis. However, rearranged bands identical to that of
      the lymph node biopsy specimen were detected by PCR in the peripheral and marrow
      blood of one of them. This PCR technique has been shown to have a sensitivity of
      0.1 per cent in our previous report and may be more useful than morphology alone
      or Southern analysis in detecting minimal lymphomatous involvement in the
      peripheral blood and bone marrow at the time of initial diagnosis. Further
      clinical correlation is required to confirm the finding.

PMID- 1398512
TI  - Proliferation in non-Hodgkin's lymphomas as determined by immunohistochemical
      double staining for Ki-67.
AB  - The authors have studied proliferation (growth fractions) in non-Hodgkin's
      lymphomas (NHL) using an immunohistochemical double staining technique with the
      monoclonal antibody (MoAb), Ki-67, in order to clarify the relationships between
      histologic type, proliferation and prognosis. The percentages of Ki-67 positive
      (Ki-67+) cells in B cell lymphomas were higher for diffuse lymphomas than for
      follicular lymphomas and increased in order from small to large cell types. In
      addition, the percentage of Ki-67+ cells in B cell lymphomas inversely correlated
      with survival in months (n = 33 r = -0.54 p < 0.01). These results indicate that
      the percentage of Ki-67+ cells in B cell lymphomas correlates with histologic
      type and prognosis. Although the prognosis of T cell lymphomas is considered
      worse than that of B cell lymphomas, the percentage of Ki-67+ cells was lower, in
      general, in T cell lymphomas than in B cell lymphomas. These data indicate that
      proliferation in T cell lymphomas does not correlate with survival.

PMID- 1398513
TI  - 'Aggressive' low grade lymphocytic lymphomas can be identified by flow cytometric
      S-phase determinations.
AB  - Forty-five patients with low grade non-Hodgkin's lymphomas were studied with
      respect to the fraction of S-phase cells in fresh tumour material by flow
      cytometric analysis. Patients with stage I lymphomas were treated with
      radiotherapy, patients with stage II-IV lymphomas with Prednimustine (Sterecyt).
      Patients with lymphocytic lymphomas of CLL type were only treated if they had
      symptoms. Median S-phase fraction in the samples was 2.0 per cent. A
      significantly shorter survival was found for patients with lymphocytic lymphomas
      with S-phase fractions > 2.0 per cent compared with cases showing lower S-phase
      fractions. No significant difference in survival was found in the subgroups of
      immunocytic or follicular and follicular/diffuse centroblastic/centrocytic
      lymphomas. In a Cox multivariate analysis, in which also age, constitutional
      symptoms, stage and morphology were included, the fraction of S-phase cells was
      found to be a statistically significant, prognostic parameter for low grade
      lymphomas, mainly due to the result in the subgroup of lymphocytic lymphomas.

PMID- 1398515
TI  - In vitro differentiation of a Hodgkin's disease derived cell line.
AB  - We have examined the Hodgkin's disease derived cell line Co in terms of its
      capacity to differentiate in vitro. Co cells show the characteristics of immature
      T cells and express CD3 molecules in the cytoplasm. On activation with 12-O
      tetradecanoylphorbol-13-acetate (TPA) these cells express the CD3 antigen and the
      T cell receptor alpha beta (TCR alpha beta) on the cell surface. Surface
      expression of the activation marker CD25 (IL2 receptor) was also greatly
      increased, whereas CD4 and CD8 levels were not altered. Supernatants of TPA
      stimulated Co cells contained the cytokines IL2, IL3, IL4 and IL8, whereas these
      cytokines were not detected in the supernatants of untreated cells. Different
      subclones of the Co cell line differed in their response to TPA with respect to
      the induced CD3 and TCR expression. Our data demonstrate that a Hodgkin's disease
      derived cell line can be induced to differentiate in vitro from a pre-T cell
      phenotype towards a more mature T cell. It is possible that similar processes may
      occur in Hodgkin's disease in vivo.

PMID- 1398516
TI  - Solitary plasmacytoma of bone: clinical features, treatment and survival.
AB  - Eleven patients with solitary plasmacytoma of bone were seen between 1978 and
      1991. A retrospective review of the clinical features, treatment and survival of
      these patients was made with the aim of helping to define those at risk for early
      development of myeloma. Nine patients (82 per cent) had paraparoteinemia at
      diagnosis. Treatment consisted of local irradiation plus or minus surgery (nine
      patients) and surgery alone (two patients). No patient received adjuvant
      chemotherapy. One patient had evidence of both generalized osteopenia and
      immunoparesis, and progressed to myeloma within six months. Four patients (36 per
      cent) progressed to myeloma. All of these had paraprotein levels which continued
      to rise following initial treatment. Three patients died of myeloma at 12, 81 and
      144 months and the other patient is alive with myeloma at 76 months. Patients
      without paraproteinemia at presentation or whose paraprotein decreased after
      treatment did not progress to myeloma. Three patients have been followed for 8,
      11 and 19 years with no evidence of myeloma. Failure of paraprotein to clear
      after local treatment suggests occult disseminated disease and is predictive of
      later development of overt myeloma.

PMID- 1398514
TI  - Bone mineral density (BMD) in patients with lymphoma: the effects of
      chemotherapy, intermittent corticosteroids and premature menopause.
AB  - Young women with a chemotherapy-induced early menopause are theoretically at
      considerable risk of developing post-menopausal osteoporosis with problems
      developing earlier and more severely. In this study bone mineral density (BMD)
      measurements were made, using a dual-energy X-ray absorptiometer (DXA), at the
      spine and hip of 50 young women who had been treated for lymphoma, 24 of whom
      were post-menopausal and 78, healthy age-matched controls. On analysis of the
      results, there was no significant difference between the control group and the 26
      post-treatment, pre-menopausal patients, but the BMD levels were significantly
      lower than the controls in the post-menopausal group particularly in 16 patients
      who had been menopausal greater than 18 months. The results confirm that these
      young women with treatment-induced premature menopause are at considerable risk
      of developing osteoporotic problems. Early recognition of this is important so
      that preventative measures with hormone replacement therapy can be initiated
      where this is safely possible. The results also indicate that chemotherapy for
      lymphoma (cytotoxics and high dose intermittent steroids), are unlikely to
      contribute directly to the lowering of the BMD of these patients.

PMID- 1398518
TI  - Verapamil preferentially potentiates in-vitro cytotoxicity of vincristine on
      malignant lymphoid cells.
AB  - Verapamil has been shown to overcome acquired drug resistance to vincristine in
      P388 leukemia both in vitro and in vivo. To study the selectivity of this action,
      the effect of addition of verapamil on the cytotoxicity of vincristine was
      studied using lymphocytes from eight patients with chronic lymphocytic leukemia
      (CLL), lymphoblasts from a T-acute lymphoblastic leukemia (T-ALL) cell line (GM
      3639), and peripheral blood lymphocytes (PBL) from eight normal healthy
      volunteers. Using the differential staining cytotoxicity (DiSC) assay, we
      demonstrated that verapamil at 1 microM concentration potentiated the in-vitro
      cytotoxicity of vincristine on CLL and GM 3639 cells in concentrations of 0.04
      0.25 micrograms/l. There was however, no enhancement of cytotoxicity noted
      against the control PBL. The data demonstrate that verapamil preferentially
      enhances the in-vitro cytotoxicity of vincristine on CLL and GM 3639 cells but no
      enhancement of cytotoxicity is seen against PBL.

PMID- 1398517
TI  - Acute myelogenous leukemia (AML) and diabetes insipidus (DI): further association
      with monosomy 7.
AB  - Diabetes insipidus (DI) is a rare complication of acute myelogenous leukemia
      (AML). Five of the six such cases described in the literature who had banded
      chromosomal studies performed had monosomy 7 and the sixth patient had
      del(7)(q22). A further case of AML complicated by DI in whom banded chromosomal
      studies revealed a complex karyotypic abnormality, including monosomy 7, is
      reported. The association between monosomy 7 and DI in AML appears specific but
      the reason for this association remains unclear.

PMID- 1398519
TI  - Diagnostic difficulties in 'non-mycotic' cutaneous lymphoproliferative diseases.
AB  - The diagnosis of cutaneous lymphoproliferative diseases is an area of bewildering
      complexity to many histopathologists. This article concentrates on 'non-mycotic'
      cutaneous diseases. The 'current state of the diagnostic art' is critically
      assessed. Cutaneous 'pseudolymphoma' is relegated to the position of an aid
      memoire and is not a diagnosis. Inadequacies in the classification of cutaneous
      lymphoma are discussed and the non-specificity of many histopathological features
      is highlighted. The status of specific entities is analysed and the contribution
      of modern investigative techniques in diagnosis is evaluated. This includes
      cutaneous T-cell lymphomas with a detailed consideration of large cell lymphoma
      heterogeneity. Cutaneous B-cell diseases are shown to be an unresolved diagnostic
      maze and the necessity for new clearly defined diagnostic criteria is emphasized.
      Evidence is presented to show that many cutaneous lymphoproliferative diseases
      lie on continuous spectra that, initially, are probably antigenically driven, and
      that a diagnosis is best achieved by a multifaceted approach. This is exemplified
      by cutaneous diseases that have origins from both B- (cutaneous lymphoid
      hyperplasia/lymphoma) and T-cells (lymphomatoid papulosis, lymphomatoid
      granulomatosis and mycosis fungoides). The future diagnostic role of the
      polymerase chain reaction and cytogenetic analysis is discussed. Intriguingly,
      recent molecular evidence has shown that lymphomatoid papulosis, cutaneous T-cell
      lymphoma, CD30 positive large cell lymphoma and Hodgkin's disease can originate
      from a single T-cell clone and display an identical chromosomal translocation and
      T-cell receptor rearrangement. Careful clinico-pathological correlation combined
      with prolonged patient follow-up remains the gold standard for diagnosis.

PMID- 1398520
TI  - Stereological estimates of nuclear volume in carcinoma of the ampulla of Vater.
AB  - The stereological estimate of mean nuclear volume is an objective and
      reproducible method of measurement of nuclear size in terms of absolute volume.
      We have used this method to study carcinomas of the ampulla of Vater. Our study
      includes 21 cases--five papillary and 16 intestinal--all treated by the same
      surgical procedure. The volume-weighted mean nuclear volume (nuclear nu v) and
      the mean nuclear area were calculated. The mean volumes of nuclear nu v were
      significantly different (P less than 0.01) between the papillary and intestinal
      carcinomas, but no differences were found between normal mucosa and papillary
      carcinoma. The variance was significantly larger in the intestinal group than the
      papillary and normal groups. The nuclear nu v showed a significant association
      with survival, larger nuclear nu v (greater than 150 microns 3) being associated
      with a lower survival rate.

PMID- 1398521
TI  - A major solid undifferentiated carcinoma pattern correlates with tumour
      progression in locally advanced prostatic carcinoma.
AB  - Solid undifferentiated carcinoma was the major microscopic pattern in 24
      prostatic carcinomas, 12 of which were clinically recurrent. Tumour cells were
      uniform, with moderately hyperchromatic nuclei and indistinct cytoplasm, and were
      arranged in solid or focally irregular aggregates. In areas, the tumour cells
      were large with vesicular nuclei, nucleoli and more abundant cytoplasm. In
      previous specimens, solid undifferentiated carcinoma was absent or was a minor
      pattern. Twenty of 23 cases showed prostate specific antigen and prostatic acid
      phosphatase immunoreactivity, and nine of 17 cases contained scattered
      argyrophilic or chromogranin-immunoreactive cells. On proliferating cell nuclear
      antigen immunostaining of 12 specimens, the mean tumour proliferative fraction in
      solid undifferentiated carcinoma (range: 10.5-18%) was greater than in areas of
      grade 3 prostatic carcinoma (range: 3-6%). In all 22 stage C and D cases, there
      was a close correlation with clinical evidence of tumour progression, and the
      overall 2-year survival rate was only 16.7%. It is concluded that a major solid
      undifferentiated pattern correlates with increased biological aggressiveness and
      a poor prognosis in locally advanced prostatic carcinoma.

PMID- 1398522
TI  - Intra-patient variation between breast cancer axillary lymph node metastases
      using quantifiable features.
AB  - The intra-patient variations of some clinically relevant quantifiable features,
      between axillary lymph node metastases were evaluated in 44 breast cancer
      patients. In all lymph node metastases detected (range 2-33 per patient), the
      mitotic figures were counted, the volume percentage epithelium was assessed and
      the mean nuclear area was measured. The intra-patient variation for each
      quantifiable feature was expressed by the coefficient of variation (CV). Since
      the measurement techniques used introduce a certain, well known variation
      themselves because of sampling and measurement errors, the CVs found had to be
      greater than methodological tolerance limits (established in previous studies) to
      be interpreted as indicating biological variation. The CVs exceeded the
      methodological tolerance limits in 86% of the cases for the mitotic count, in 48%
      of the cases for the volume percentage epithelium, and in 47% of the cases for
      the mean nuclear area. This indicated that in these cases, the variation found in
      the quantifiable features could not be explained by sampling or measurement
      errors and should be regarded as real biological variation. Furthermore, the
      variation in the quantifiable features studied showed a significant positive
      correlation with the number of lymph node metastases. Thus, there may be
      considerable intra-patient variation in quantifiable features between axillary
      lymph node metastases in breast cancer. This may indicate that these lymph node
      metastases originate independently from different clones within the primary
      tumour, that they are independently formed in different stages of tumour
      development, or that they, as an expression of intrinsic tumour heterogeneity,
      may develop in different directions from the start.

PMID- 1398523
TI  - Thymic carcinosarcoma associated with a spindle cell thymoma: an
      immunohistochemical study.
AB  - A case of thymic carcinosarcoma associated with a spindle cell thymoma in a 71
      year-old woman is reported. Histological and immunohistochemical studies of the
      carcinosarcoma showed two quite different components: the sarcomatous component
      included cells with myoid differentiation which stained for desmin and muscle
      specific actin, and some isolated cells which stained positively for low
      molecular weight cytokeratin, while the carcinomatous component, which formed
      less than 10% of the tumour, showed an epithelial phenotype, being positive for
      low and high molecular weight cytokeratin and epithelial membrane antigen. The
      thymoma cells showed epithelial markers, and a few cells were also positive for
      desmin and muscle specific actin. The rarity of this tumour and its possible
      histogenesis are discussed.

PMID- 1398524
TI  - Design of an expert system and its application to dermatopathology.
AB  - Expert systems are computer programs which use inference and knowledge to solve
      problems which usually require the expertise of a human specialist. This paper
      examines the application of expert systems to histopathology and explains their
      construction by describing the design of an expert system 'dermdx', intended to
      aid in the interpretation and diagnosis of biopsies of inflammatory diseases of
      the skin. The system consists of an expert shell, which performs the inference,
      and a rule-base, which contains the knowledge with which the system operates. The
      system can be easily updated or adapted to other tasks.

PMID- 1398525
TI  - Chronic neurological dysfunction attributable to a ganglioglioma.

PMID- 1398526
TI  - Sebaceous glands and hair follicles in the cervix uteri.
AB  - We report a case of ectopic ectodermal structures in the ectocervix of a 51-year
      old female. Sebaceous glands and numerous abnormal hair follicles were present in
      the stroma of an otherwise normal cervix.

PMID- 1398527
TI  - Necrotizing sialometaplasia (adenometaplasia) of the trachea.
AB  - Necrotizing sialometaplasia is a benign condition first described in minor
      salivary glands of the soft palate with morphological changes which can be
      misinterpreted as squamous-cell carcinoma. Similar lesions have been subsequently
      reported in other locations including major salivary glands, lip, breast and skin
      (the term syringometaplasia has been applied for the latter). We report three
      cases of such a process involving submucosal glands in the trachea following
      prolonged translaryngeal intubation.

PMID- 1398528
TI  - Ceroid granuloma of the uterine cervix.
AB  - An excision biopsy was taken from a 59-year-old woman with a small dark-brown
      lesion on the anterior lip of the cervix. The histology revealed an ulcerated
      surface epithelium with a band-like infiltrate of pigment containing macrophages
      in the subepithelial zone. Histochemical examination of the specimen revealed
      that the pigment was ceroid. This is, to the best of our knowledge, the first
      case report of ceroid granuloma of the uterine cervix.

PMID- 1398529
TI  - An unusual pulmonary plasmacytoma.

PMID- 1398530
TI  - From slow virus to prion.

PMID- 1398532
TI  - Recurrent epidermal cysts of the breast.

PMID- 1398531
TI  - Giemsa stain for histological diagnosis of bacillary angiomatosis.

PMID- 1398533
TI  - Recombinant DNA technology and its diagnostic applications.
AB  - As yet recombinant DNA technology does not appear to have widespread diagnostic
      application in pathology. However, it does have a useful role to play in specific
      circumstances in at least three main areas: a it can provide precise diagnostic
      information about genetic diseases, allowing appropriate counselling, and
      indicating future directions for research on therapeutic intervention, e.g. gene
      therapy; b micro-organisms can be identified more sensitively and specifically,
      in fresh or fixed tissue samples, and their genomes can be analysed in fine
      detail, providing information relevant to the aetiology, epidemiology and
      pathogenesis of many diseases; c in tumour pathology the main application so far
      has been to resolve diagnostic problems associated with leukaemias and lymphomas,
      when other diagnostic procedures have been inconclusive. Specific chromosomal
      translocations, involving recognized genes, are particularly amenable to
      diagnosis by these means. Diagnostic applications to solid tumours are yet to be
      identified, although significant insights into tumorigenesis have been obtained,
      and these may ultimately lead to the development of useful markers for prognostic
      and therapeutic purposes.

PMID- 1398534
TI  - Pathogenesis of congenital cystic adenomatoid malformation of the lung.
AB  - Congenital cystic adenomatoid malformation is a rare developmental abnormality of
      the lung. In most earlier reported cases, the anatomy of the bronchial tree was
      poorly documented. We describe four cases studied following autopsy. Post-mortem
      bronchography or serial microscopical examination showed segmental bronchial
      absence or atresia in each of them. Our observations provide further evidence
      pointing to bronchial atresia as being the primary defect leading to the
      development of congenital cystic adenomatoid malformation. The morphology of the
      lesion, i.e. the type of malformation, is determined by the extent of dysplastic
      lung growth beyond the atretic segment. The aetiology of the bronchial atresia is
      probably heterogeneous and may either represent a primary malformation, or be the
      result of vascular disruption.

PMID- 1398535
TI  - p53 expression is common in malignant mesothelioma.
AB  - The p53 tumour suppressor gene has been shown to be frequently mutated in a wide
      range of human neoplasms. This is accompanied by increased levels of p53 protein
      which become immunologically detectable in pathological material. We have
      investigated the possibility that the differential diagnosis between reactive and
      neoplastic mesothelium might be resolved using a polyclonal serum raised to human
      p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed
      p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma
      showed p53 staining. We can thus infer that abnormalities of p53 appear to be a
      common event in malignant mesothelioma and that p53 immunostaining may be of
      value in the distinction of malignant mesothelioma from reactive hyperplasia.

PMID- 1398536
TI  - Light microscopic and ultrastructural distribution of type VI collagen in human
      liver: alterations in chronic biliary disease.
AB  - We have investigated the distribution of type VI collagen in normal human liver
      obtained from cadaveric renal transplant donors, using a peroxidase
      antiperoxidase method for light microscopic visualization, and an immunogold
      labelling method for ultrastructural localization. The distribution was compared
      with that of the more abundant interstitial collagen type III, using antibodies
      to amino terminal procollagen type III. Staining for type VI collagen was
      identified in Glisson's capsule, in portal tract stroma and within the space of
      Disse. Perisinusoidal staining showed intra-acinar heterogeneity with the
      intensity in acinar zones 2 and 3 being greater than in zone 1. Type III collagen
      was also found in the space of Disse although no significant intra-acinar
      variation in staining intensity was noted. Immuno-gold labelling for type VI
      collagen was demonstrated on amorphous or microfilamentous material lying
      between, and occasionally appearing to interconnect, cross-striated collagen
      fibrils, whereas labelling for amino terminal procollagen type III was
      exclusively on fibrils. Intracellular staining for type VI collagen was noted in
      perisinusoidal (lto) cells. These results confirm that type VI collagen is a
      ubiquitous constituent of the normal hepatic extracellular matrix and suggest
      that it may be synthesized by perisinusoidal (lto) cells. The distribution of
      type VI collagen was also studied in biopsy material from patients with different
      histological stages of primary biliary cirrhosis. Intense staining was noted
      around proliferating bile ductules within developing fibrous septa and in
      established septa of cirrhotic liver. These observations indicate that this
      'minor' matrix component may play an important role in hepatic fibrogenesis.

PMID- 1398537
TI  - Collagenous and basement membrane proteins of chordoma: immunohistochemical
      analysis.
AB  - Tissue localization of collagenous and basement membrane proteins in the
      extracellular matrix of five sacro-coccygeal chordomas and human fetal notochords
      was examined immunohistochemically to assess the implications for the
      histogenesis and histological diagnosis of chordoma. Human fetal notochords and
      conventional chordomas both exhibited basement membrane proteins (such as type IV
      collagen and laminin) and type VI collagen on the surfaces of cellular cords.
      Type II collagen, a main structural protein of cartilage, was also present in
      both tissues. In the chordomas, however, type II collagen was not so widespread
      as it was in the notochords, and the predominant collagenous protein was type I.
      In contrast, an altered deposition of these proteins was noticed in a recurrent
      tumour which, histologically, showed considerable atypia and eventually
      metastasized to the liver. The characteristic cartilage-type and basement
      membrane proteins disappeared and unusual collagen types, such as types III and
      V, appeared in the stroma. The results further support the notochordal origin of
      chordoma and suggest that the immunohistochemistry of collagenous and basement
      membrane proteins may be a helpful criterion for the histological diagnosis and
      prediction of the biological aggressiveness of chordomas.

PMID- 1398538
TI  - Detection of immunoglobulin light chain mRNA in nodular sclerosing Hodgkin's
      disease by in situ hybridization with biotinylated oligonucleotide probes
      compared with immunohistochemical staining with poly- and monoclonal antibodies.
AB  - In order to elucidate the origin of the Hodgkin's and Reed-Sternberg cells, the
      expression of immunoglobulin kappa- and lambda light chain mRNA in 23 cases of
      nodular sclerosing and two cases of mixed cellularity Hodgkin's disease was
      examined by in situ hybridization using biotinylated oligonucleotide probes and
      compared with immunohistochemical staining with mono- and polyclonal antibodies
      against immunoglobulin kappa- and lambda light chains. No hybridization signals
      were seen in Hodgkin's or Reed-Sternberg cells in any of the cases. Polyclonal
      staining with polyclonal anti-immunoglobulin light chain antibodies was seen in
      Hodgkin's and Reed-Sternberg cells in 12 cases of nodular sclerosis and in two
      cases of mixed cellularity and with monoclonal antibodies in three cases of
      nodular sclerosis, but in no cases of mixed cellularity. In all cases, there was
      polyclonal labelling of plasma cells with both the oligonucleotide probes and the
      antibodies. In five cases, the Hodgkin's and Reed-Sternberg cells were also
      stained with one of the B-cell antibodies L26, MB2 or LN1. Lack of mRNA signals
      in Hodgkin's and Reed-Sternberg cells might indicate that these cells in
      Hodgkin's disease of the nodular sclerosis subtype are either not B-cell derived
      or they are early B-cells (precursor B-cells) not yet able to produce
      immunoglobulin light chain mRNA, at least not at a level detectable by in situ
      hybridization. Immunohistochemical staining of Hodgkin's and Reed-Sternberg
      cells, however, with antibodies against immunoglobulin kappa and lambda light
      chains may be explained by cellular uptake of the light chains, but the
      difference in reactivity between poly- and monoclonal antibodies cannot be
      explained at present.

PMID- 1398539
TI  - Focal oxyntic gland atrophy with endocrine cell hyperplasia in Zollinger-Ellison
      syndrome during omeprazole treatment.
AB  - Development of focal gland atrophy of the oxyntic mucosa was found in two
      patients with the Zollinger-Ellison syndrome undergoing long-term treatment with
      omeprazole. The atrophic areas revealed florid proliferation of endocrine cells
      in the form of both intraglandular crescents and micronodular hyperplasia. This
      proliferation was significantly more pronounced than in the remaining non
      atrophic mucosa. The possible relationship of these changes to long-standing
      pharmacological therapy for gastric acid suppression is discussed.

PMID- 1398540
TI  - Sporadic medullary microcarcinoma of the thyroid.

PMID- 1398541
TI  - Concurrence of a symptomatic encapsulated follicular carcinoma, an occult
      papillary carcinoma and a medullary carcinoma in the same patient.

PMID- 1398542
TI  - Spontaneous post-partum rupture of a patent ductus arteriosus.

PMID- 1398543
TI  - Intracellular calcification: an unusual histological feature of acute
      myocarditis.

PMID- 1398544
TI  - Carcinoma arising in a diverticulum of sigmoid colon.

PMID- 1398545
TI  - Sex cord-like pattern leiomyomatosis peritonealis disseminata: a hitherto
      undescribed feature.

PMID- 1398546
TI  - Post-operative necrotizing granulomas of the thyroid.

PMID- 1398547
TI  - The histiocytoses of childhood.

PMID- 1398548
TI  - Spongiform encephalopathies (or prion diseases)

PMID- 1398549
TI  - Sclerosing lymphocytic lobulitis and autoimmune mastitides.

PMID- 1398550
TI  - Antiphonal duetting and sex hormones in the tropical bush shrike Laniarius
      funebris (HARTLAUB).
AB  - We investigated changes in antiphonal duetting with phases of reproduction and
      circulating levels of luteinizing hormone, testosterone, and estradiol in slate
      colored boubous (Laniarius funebris) breeding in aviaries. Frequency of overall
      male singing did not vary with reproductive phase while frequencies of female
      singing and female vocal responses to male song were reduced during incubation
      and feeding of nestlings. This resulted in significant changes in frequency of
      duetting. Males sang the sexual song type M1 more often during courtship and nest
      building than during the nestlings phase. Their territorial song types M2 and M4
      did not vary with breeding phase. Females were less responsive to M1 during
      incubation and to M2 during the nest building and nestlings than during the
      courtship phase. Plasma levels of luteinizing hormone and testosterone increased
      in males from the prebreeding to the courtship phase. While testosterone
      decreased already during nest building and remained low during subsequent phases
      of reproduction, luteinizing hormone decreased during incubation and feeding of
      nestlings. Female luteinizing hormone levels were highest during nest building.
      Female estradiol levels decreased from nest building to incubation and increased
      again during subsequent nest building. Female testosterone levels were low but
      not basal and did not vary with phase. Neither the overall male and female
      singing frequencies nor the frequencies of male song types were correlated with
      hormonal state. However, female participation in territorial duets M4 correlated
      positively with their testosterone levels. It is suggested that in this
      monogamous, duetting species with prolonged pairbonds behavioral cues between the
      mates are more important than the hormonal state in control of male and female
      singing.

PMID- 1398551
TI  - Social influences on reproductive development and fertility in female Djungarian
      hamsters (Phodopus campbelli).
AB  - Social influences on the sexual maturation of female Djungarian hamsters were
      investigated in two experiments. In the first experiment females were housed from
      weaning with an adult male, by themselves, or with a weanling sister. Maturation
      was accelerated in females housed with males as indicated by younger age at first
      ovulation, increased rates of ovarian and uterine growth, and lower LH levels at
      some ages. Maturation was delayed in females housed with sisters compared to
      those housed alone as measured by time of first ovulation and by lower estradiol
      levels at some ages. The most marked differences between groups occurred 8 to 12
      days after weaning, suggesting that events during this period are particularly
      important in the social mediation of sexual maturation. In the second experiment
      the effects of reproductive suppression (caused by living with a sister) on the
      subsequent fertility of females housed with males were examined. If male-female
      pairs were housed in clean cages, no effects were observed; however, pairs housed
      in cages previously soiled by the female and her sister had fewer young surviving
      until 1 week of age despite no differences in the age of pregnancy onset or in
      the initial litter size. Thus, even cues present in unrenewed soiled bedding may
      have subtle but long lasting effects on reproductive function.

PMID- 1398552
TI  - Influences of exogenous epinephrine on two reproductive parameters in female
      mice: disruption of receptivity but not implantation.
AB  - Diverse stressors impede female receptivity and fertility. Since epinephrine is
      released from the adrenal during stress, it might play a role in stress-induced
      disruptions of female reproductive parameters. Experiment 1 examined whether
      exogenous epinephrine would disrupt lordosis behavior in estrogen- and
      progesterone-treated ovariectomized female mice. Single dosages of 20 and 40
      micrograms almost eliminated sexual receptivity. Experiments 2 and 3 examined
      whether chronic dosages of epinephrine shortly after insemination would lead to a
      failure of implantation of mouse embryos. Results indicated that epinephrine had
      little effect on the number of dams delivering pups, the number of pups born,
      litter weight, or the number of stillbirths.

PMID- 1398553
TI  - Development of partner preferences in female prairie voles (Microtus
      ochrogaster): the role of social and sexual experience.
AB  - Prairie voles (Microtus ochrogaster) exhibit a monogamous mating system
      characterized by long-term pair bonds between mates. The purpose of this study
      was to examine the effect of cohabitation time and sexual experience on the
      development of pair bond formation in female prairie voles. Females that were
      allowed to cohabit for 24 hr or more, with or without mating, exhibited a strong
      social preference for a familiar partner versus a strange male. Females that
      cohabited and mated for 6 hr showed strong preferences for a familiar partner,
      while cohabitation for less than 24 hr, without mating, did not result in
      preferences for the familiar male. These results indicate that mating was not
      essential for partner preference formation; however, preferences developed more
      rapidly when mating occurred.

PMID- 1398554
TI  - Role of glucocorticoids in the stress-induced suppression of testicular
      steroidogenesis in adult male rats.
AB  - We have examined the role of glucocorticoids in the stress-induced inhibition of
      testicular steroidogenesis. Immobilization (3 hr) reduced plasma testosterone (T)
      levels to 24% of control values but did not affect plasma LH levels. This
      reduction was partially reversed by in vivo injections of the antiglucocorticoid,
      RU486, prior to the stress session at a dose of 10 mg/kg BW, but not at 1.0 or 50
      mg/kg BW. Stressed rats that were treated with 10 mg/kg BW RU486 had twofold
      higher plasma T levels than vehicle-treated stressed animals. Injections of RU486
      did not affect plasma LH levels in control or stressed rats and did not affect T
      levels of unstressed rats. Stressed rats had eightfold higher plasma
      corticosterone levels than controls, and RU486 had no effect on control or stress
      levels of corticosterone. The possible role of glucocorticoids in mediating the
      effect of stress on testicular T production was investigated also in vitro by
      incubating testicular interstitial cells from unstressed rats for 3 hr with
      corticosterone (0, 0.01, 0.1, or 1.0 microM) or dexamethasone (0, 0.001, 0.01, or
      0.1 microM), followed by an additional 2 hr with hCG (0, 25, 50, or 100 microIU).
      Both corticosterone and dexamethasone inhibited hCG-stimulated T production in a
      dose-dependent manner. Cells incubated with the highest concentration of either
      of the glucocorticoids showed significantly reduced responses to hCG stimulation.
      In the absence of hCG, in vitro T production was not affected by dexamethasone or
      0.01 and 0.1 microM corticosterone. However, the highest dose of corticosterone
      (1.0 microM) produced a 63% elevation in basal T production. Coincubation of
      testicular interstitial cells with corticosterone (1.0 microM) or dexamethasone
      (0.1 microM) and RU486 (0.01, 0.1, and 1.0 microM) reversed the glucocorticoid
      induced suppressions of T production in a dose-dependent manner. Our results
      suggest that during stress increases in plasma levels of glucocorticoids in male
      rats act via glucocorticoid receptors on testicular interstitial cells to
      suppress the testicular response to gonadotropins, and that the decline of
      testosterone production during immobilization stress is in part mediated by a
      direct action of glucocorticoids on the testis.

PMID- 1398555
TI  - The effect of estrogen treatment on scopolamine inhibition of lordosis.
AB  - Previous evidence indicates that the cholinergic muscarinic antagonist,
      scopolamine, inhibits lordosis in female rats. In the experiments reported here,
      the effects of various doses and repeated administrations of estrogen on the
      scopolamine inhibition of lordosis were examined. In the first experiment,
      intraperitoneal injections of scopolamine (1 mg/rat) completely inhibited
      lordosis in ovariectomized rats primed with low doses of estradiol benzoate (0.25
      or 0.5 micrograms for 3 days) and progesterone (500 micrograms). However,
      scopolamine was significantly less effective in inhibiting lordosis in females
      primed with a higher dose of estradiol benzoate (25 micrograms for 3 days) and
      progesterone (500 micrograms). When hormone priming was repeated on subsequent
      weeks, scopolamine continued to inhibit lordosis in females that received 0.25
      micrograms estradiol benzoate but was less effective in females primed with 0.5
      micrograms. Scopolamine failed to inhibit lordosis in females treated with 25
      micrograms estradiol benzoate on these later tests. In the second experiment,
      various doses of scopolamine (1, 2, or 4 mg/rat) were administered
      intraperitoneally to females primed with the highest dose of estradiol benzoate
      (25 micrograms) and progesterone (500 micrograms). Lordosis was inhibited equally
      by all scopolamine doses during the first week. As in the first experiment,
      scopolamine failed to inhibit lordosis at all doses on subsequent weeks of
      testing. These results indicate that the ability of scopolamine to inhibit
      lordosis is reduced by increasing the dose or the number of estrogen exposures.
      Because higher doses of scopolamine failed to restore its inhibitory effect on
      lordosis an upregulation of muscarinic receptors by estrogen cannot account for
      the reduced effectiveness of scopolamine.

PMID- 1398556
TI  - Behavioral and cardiac responses after intracerebroventricular corticotropin
      releasing hormone (CRH) administration: role of adrenal cortical hormones.
AB  - Intracerebroventricularly (icv) administered corticotropin-releasing hormone
      (CRH) produces a dose-dependent increase in heart rate in association with
      behavioral activation. The present study was designed to investigate whether
      these CRH-induced responses are dependent on adrenal function. The effects of
      adrenalectomy (ADX) and subsequent corticosterone replacement were studied.
      Administration icv of 300 ng of CRH failed to produce behavioral activation and
      tachycardia in ADX rats. Corticosterone replacement restored the CRH-induced
      behavioral response to preoperative levels, whereas the CRH-induced tachycardia
      was partially restored. This latter result may be related to the fact that the
      baseline heart rate of ADX animals appeared to be significantly higher than that
      of corticosterone-treated ADX animals. It is concluded that circulating adrenal
      corticosterone in ADX rats is involved in the expression of the behavioral and
      cardiac effect of central CRH.

PMID- 1398557
TI  - Fear and distress in Japanese quail chicks of two lines genetically selected for
      low or high adrenocortical response to immobilization stress.
AB  - Behavioral and adrenocortical reactivity to stressful stimulation was examined in
      12- and 13-day-old chicks of two lines of Japanese quail selected over several
      generations for exaggerated (HS: high stress) or reduced (LS: low stress) plasma
      corticosterone (B) response to brief immobilization stress. Plasma B
      concentrations and tonic immobility (TI) fear reactions were measured in
      unstressed (control) and stressed (overnight cooping) chicks of both lines. The
      stress treatment was applied over a period of 12-20 hr and it involved capture by
      the experimenter, inescapable exposure to an unfamiliar environment and to
      strange conspecifics, reductions in ambient temperature and floor space, and the
      deprivation of food and water. Chicks of the HS line were more susceptible to the
      induction of TI and they remained immobile longer than did LS chicks. Therefore
      HS chicks were considered to be more fearful than their LS counterparts. Stress
      treatment elicited a marked adrenocortical response that was more pronounced in
      HS than in LS chicks. Stress treatment also increased susceptibility to TI but
      did not significantly affect the duration of immobility. These findings suggest
      that selecting the quail for differential corticosterone response to a particular
      stressor had exerted an unconscious and concomitant effect on underlying
      fearfulness as well as on their adrenocortical reactivity to several other
      stressful situations. The results are further discussed in terms of a putative
      relationship between adrenocortical activation and fearfulness.

PMID- 1398558
TI  - Testosterone and opioids interact to regulate feeding in a male migratory
      songbird.
AB  - A male migratory songbird (dark-eyed junco, Junco hyemalis) was used as a model
      for studies on the influence of testosterone (T) on feeding, and on interactive
      effects on this behavior between T and the opioid antagonist naloxone
      hydrochloride (Nal). Administered chronically to birds exposed to nonstimulating
      photoperiods, T increased food intake by 30-58% without altering the body mass,
      the fat index, or the standard metabolic rate. An intramuscular injection of Nal
      decreased feeding temporarily in a dose-related manner. T-treated juncos
      exhibited a decreased sensitivity to the anorexic influence of Nal
      administration, demonstrating that T interacts with opioids to control food
      consumption. Neuroendocrine mechanisms that potentially account for this
      interaction are discussed.

PMID- 1398559
TI  - Erectile function and bulbospongiosus EMG activity in estrogen-maintained
      castrated rats vary with behavioral context.
AB  - Electromyographic (EMG) activity in the bulbospongiosus muscles (BS) was recorded
      to monitor potential castration-induced alterations in muscle activity during
      copulation and reflexive erections. EMG recordings were made from intact male
      rats and from castrated rats maintained from 7 to 50 days on estradiol benzoate
      (300 micrograms/day) or testosterone (200 micrograms/day). Despite a 40-50%
      postcastration reduction in the weight of the BS and accessory sexual glands in
      estrogen-treated rats, the pattern of EMG activity during copulation was similar
      across groups. In estradiol-treated males, the EMG burst frequency during mounts
      and burst duration during intromissions exceeded the parameters of intact males
      and of castrated males maintained on testosterone. Between intromissions, and
      following ejaculatory patterns, estrogen-treated males displayed spontaneous
      muscle bursts accompanied by visually confirmed erection of the glans penis, but
      these males quickly lost the capacity for reflexive erections. These data
      demonstrate that despite castration-induced atrophy of the penile muscles and,
      presumably, their spinal motor nuclei, the motor output to these muscles is
      maintained following androgen removal. The capacity for substantial penile
      erection is retained during copulation long after reflexive erections have
      diminished.

PMID- 1398560
TI  - Year-to-year patterns of circulating levels of testosterone and corticosterone in
      relation to breeding density, experience, and reproductive success of the
      polygynous red-winged blackbird.
AB  - To determine across-year patterns in plasma testosterone (T) and corticosterone
      (B) levels in free-living birds, we took blood samples in the same 2-week
      breeding period during 4 consecutive years from territorial male red-winged
      blackbirds. We used our data to test predictions of the "challenge hypothesis" of
      T secretion and also to examine hormonal correlations with age, breeding
      experience, breeding density, and reproductive success. Average T and B levels
      across years were not significantly different. Within individuals, T levels
      between years were, in general, highly variable. T levels of males with
      territories in high-density breeding areas were significantly higher than those
      of males with territories in low-density areas. T levels were positively
      correlated with harem size and there was a trend for males with high T levels to
      fledge more offspring. We found no relationships between T and B levels and male
      age or breeding experience. Some results of the study were consistent with the
      predictions of the challenge hypothesis. This study constitutes one of the few
      examinations of across-year patterns in circulating hormone levels in wild
      populations.

PMID- 1398561
TI  - Prenatal diethylstilbestrol exposure and performance on college entrance
      examinations.
AB  - The fetal rodent brain is permanently altered by exposure to sex hormones. Long
      term effects of prenatal sex hormones on the human brain are far less clear. In
      order to explore such effects, we studied a measure of cognitive function among
      young adults who had been exposed in utero to a powerful synthetic estrogen. In a
      randomized clinical trial conducted at the University of Chicago in 1950-1952,
      1646 pregnant women were randomly assigned to receive either high doses of
      diethylstilbestrol or placebo. Women in this study gave birth to 1653 liveborn
      infants, of whom 1603 (820 sons and 783 daughters) survived to their fifteenth
      birthday. College entrance examination scores were obtained for 42% of these
      offspring. No differences in test performance were seen among exposed daughters.
      Among sons, test scores were marginally higher among the exposed, probably due to
      chance.

PMID- 1398562
TI  - Management of early postdischarge adjustment reactions following psychiatric
      hospitalization.
AB  - Psychiatric patients frequently experience serious symptoms and demonstrate
      disturbed behaviors in the very early postdischarge period. Based on 25 years of
      clinical experience, the author reviews symptoms and behaviors that can occur and
      notes that they should most often be viewed as adjustment reactions rather than
      as exacerbations of the primary illness. A team approach to management of early
      postdischarge reactions that uses a psychiatrist and psychiatric nurse is
      effective. Interventions include forewarning inpatients that problems may occur
      and helping them identify potential problems. Social skills training, learning
      therapies, and family counseling help patients prepare to cope. Accompanying
      patients home on passes during hospitalization is helpful, as is inviting them to
      visit the hospital during their first days at home. Scheduling initial office
      visits within three days of discharge is another way of easing a difficult
      transition.

PMID- 1398563
TI  - Experimental comparison of the effects of three treatment programs for homeless
      mentally ill people.
AB  - A longitudinal experimental design was used to compare the effectiveness of three
      community-based treatment programs serving homeless mentally ill people:
      traditional outpatient treatment offered by a mental health clinic, a daytime
      drop-in center, and a continuous treatment team program that included assertive
      outreach, a high staff-to-client ratio, and intensive case management. At 12
      month follow-up, clients in all three treatment programs spent fewer days per
      month homeless, showed fewer psychiatric symptoms, and had increased income,
      interpersonal adjustment, and self-esteem. Clients in the continuous treatment
      program had more contact with their treatment program, were more satisfied with
      their program, spent fewer days homeless, and used more community services and
      resources than clients in the other two programs.

PMID- 1398564
TI  - Posttraumatic stress disorder among homeless men and women.
AB  - Six hundred homeless men and 300 homeless women in St. Louis were systematically
      interviewed using the revised Diagnostic Interview Schedule that includes a
      module for assessment of posttraumatic stress disorder (PTSD). Most subjects with
      PTSD had an additional life-time psychiatric diagnosis. No consistent pattern of
      association was apparent, however, between individual diagnoses and either
      traumatic events or PTSD. In almost three-fourths of both men and women, the
      onset of PTSD had preceded the onset of homelessness. Childhood histories of
      abuse and family fighting were predictive of both traumatic events and PTSD. The
      results suggest that factors leading to PTSD in the study sample began long
      before the onset of homelessness and may overlap with factors operative in the
      genesis of homelessness.

PMID- 1398565
TI  - Homeless adults without apparent medical and psychiatric impairment: onset of
      morbidity over time.
AB  - A cross-sectional study compared characteristics of homeless adults with and
      without substance abuse, physical health problems, and history of psychiatric
      hospitalization when they first became homeless. Self-report data on demographic
      characteristics, adverse events in childhood, and history of medical disorders
      were collected from 1,399 homeless adults who used three shelters in Santa Clara
      County, California, during a five-month winter period in 1989 and 1990 (96
      percent response rate). A total of 45.6 percent of the respondents reported no
      impairments when they first became homeless. They were distinguished from those
      with impairments at onset of homelessness by their younger age, minority status,
      lower educational attainment, and lower frequency of adverse events in childhood.
      Respondents who reported no impairments when they first became homeless were
      likely to develop addictive and psychiatric disorders over time. Those who had
      been homeless five years or more reported high rates of alcohol abuse (34.5
      percent), illegal drug use (24.1 percent), and psychiatric hospitalization (20.7
      percent).

PMID- 1398566
TI  - Privilege and discharge decisions for psychiatric inpatients with dysphagia.
AB  - Psychiatric patients have an increased risk for choking compared with the general
      population because of risk factors such as medication side effects and food
      gorging. A state hospital program for managing patients with dysphagia, or
      difficulty swallowing, includes interventions such as modified diets, mealtime
      monitoring, and adjusting psychotropic medications. Clinicians may find it
      difficult to make decisions about privileges and placement for dysphagic patients
      who do not comply with dietary modifications in unsupervised settings. For many
      such patients, close supervision and even placement on a locked ward may seem
      necessary. The authors recommend a risk-benefit approach: clinicians must balance
      the safety afforded by restrictions against the benefits of increased privileges
      or placement in a less restrictive setting. Quality of life and patients'
      preferences must also be considered.

PMID- 1398567
TI  - Mental illness among homeless female veterans.

PMID- 1398568
TI  - A typology of difficult patients with long-term stays on a secure ward in Japan.

PMID- 1398569
TI  - Clinical review panels versus court hearings in treatment refusal by involuntary
      patients.

PMID- 1398570
TI  - Family attitudes that predict home placement of hospitalized psychiatric
      patients.

PMID- 1398571
TI  - Fear-based advertising and the increase in psychiatric hospitalization of
      adolescents.

PMID- 1398572
TI  - A state-university collaboration to improve state hospital nursing care.

PMID- 1398573
TI  - Partial hospitalization.

PMID- 1398575
TI  - Deinstitutionalization.

PMID- 1398574
TI  - Partial hospitalization.

PMID- 1398576
TI  - Consensus panel calls for vigorous treatment of depression in elderly.

PMID- 1398577
TI  - Research must guide services for children and adolescents.

PMID- 1398579
TI  - The practice of emergency psychiatry in rural areas.

PMID- 1398578
TI  - The educational implications of managed mental health care.

PMID- 1398581
TI  - Alcoholism in older persons: a review of the literature.
AB  - Alcohol abuse and dependence in elderly persons is of growing social concern. The
      most consistent findings of cross-sectional and longitudinal studies are that the
      quantity and frequency of alcohol consumption is higher in elderly men than in
      elderly women, as is the prevalence of alcohol-related problems. Most studies
      show a decrease with age in consumption and alcohol-related problems among heavy
      drinkers. Longitudinal studies show no changes in consumption among light
      drinkers. Elderly persons with lower incomes consume less alcohol than those with
      higher incomes. Hospitalized and outpatient populations have more problem
      drinkers, and the elderly alcoholic is at greater risk for medical and
      psychiatric comorbidity. About one-third to one-half of elderly alcoholics
      experience the onset of problem drinking in middle or late life. Outcomes seem to
      be better for those who have late-onset drinking and may be improved for those
      treated in same-age rather than mixed-age groups.

PMID- 1398580
TI  - Psychiatrists and access to abortion.

PMID- 1398582
TI  - State-university collaboration to enhance public psychiatric services in western
      Pennsylvania.
AB  - A collaboration established in 1974 between the Pennsylvania State Office of
      Mental Health and Western Psychiatric Institute and Clinic of the University of
      Pittsburgh Medical Center provides a comprehensive program of continuing mental
      health education, skills development, and program consultation to state hospitals
      and publicly funded community programs in rural and semirural western
      Pennsylvania. The authors describe the development of the program and discuss its
      current organization and activities. In 1990-91 a total of 60 faculty and 150
      staff members from the institute contributed more than 1,200 hours of direct
      programming. The collaboration's activities have broadened in both hospital and
      community sectors and currently involve all of the university's health and
      medical care schools.

PMID- 1398583
TI  - Second-quarter data from AHA Monitrend II.

PMID- 1398584
TI  - Health care reform.

PMID- 1398586
TI  - The new finance department: CQI triggers big changes in role.
AB  - As hospitals implement total quality management and CQI programs and experiment
      with patient-centered care initiatives, financial officers are moving away from
      their traditional "bean-counter" role toward a broader role as part of a
      leadership team crafting a vision of the future.

PMID- 1398585
TI  - State health reform. Five trends that will transform hospitals.
AB  - As states struggle to forge health care reform plans that meet the opposing
      objectives of cutting costs and improving access, one thing is certain: Their
      initiatives will create profound changes to health care and to hospital
      operations. In fact, five factors emerging from the state reform debate could
      drastically transform hospitals: reregulation, explosive managed care growth,
      uncertain state funding mechanisms, new insurance measures, and greater hospital
      accountability for cost and quality. "This is a wake-up call for hospitals to get
      very realistic about the cost concerns that are out there," says one hospital
      executive. Especially since these state efforts are a precursor to national
      reform.

PMID- 1398587
TI  - Making mandatory medical staff meetings more physician-friendly.
AB  - In an effort to improve hospital-medical staff relations, a number of hospitals
      are making changes in their medical staff meetings structures--putting time
      limits on meetings, modifying attendance requirements, even timing comments. One
      California hospital even uses an egg timer to facilitate the monthly meetings of
      its medical staff executive committee.

PMID- 1398588
TI  - Work redesign calls for new pay and performance plans.
AB  - TQM/CQI and patient-centered care initiatives are also spurring changes in
      hospitals' employee payment and performance systems. The tricky part is that
      those systems have to change at the same time delivery systems are changing. "We
      feel we can't first develop new care delivery systems and then spend the next two
      years adjusting compensation systems," says one executive.

PMID- 1398590
TI  - Hospitals recognize link between art and healing.

PMID- 1398589
TI  - JCAHO introduces three new areas of survey concentration.
AB  - The Joint Commission has released a new and improved 1993 Accreditation Manual
      for Hospitals. New to the manual are three chapters of standards that will be
      used to survey areas that include patient and family education and staff training
      and orientation. The manual is also shorter.

PMID- 1398592
TI  - Increased turnover ahead for hospital CEOs.

PMID- 1398591
TI  - More hospitals move toward bedside systems.

PMID- 1398593
TI  - Quality coordinator: on cutting edge of change.

PMID- 1398595
TI  - How to get your money's worth from consultants.

PMID- 1398594
TI  - Bond investors show new interest in quality of care.

PMID- 1398596
TI  - Outpatient use of cardiac caths poised for growth.

PMID- 1398598
TI  - Data watch. Trends in the use of cancer screening tests.

PMID- 1398597
TI  - Rejection of Oregon plan a setback to reform.

PMID- 1398599
TI  - Smart moves. Good management, not technology, will steer movement to outpatient
      care.

PMID- 1398600
TI  - Hospitals and medical staffs: the concept of planning takes on new meaning.
AB  - Broad trends in health care are redefining medical staff planning. Hospital CEOs
      are recognizing the critical need to involve their physicians in hospital
      strategic planning at many levels. Gone are the days when it was sufficient to
      invite medical staff members to annual planning retreats and add individual
      physicians to boards; hospitals that thrive in the 1990s will be those that have
      created strong strategic links with their physicians. At the same time, medical
      staff development planning is changing in important ways. Recent federal
      government alerts on fraud and abuse and inurement in physician-recruiting
      activities are leading hospitals to document community benefit in their
      recruitment efforts. And hospital executives now realize that changes in the
      physician market will require them to plan carefully in order to ensure a strong
      base of primary care and other much-needed physicians. These two trends present
      CEOs with multilayered challenges. Following are reports on what leading-edge
      hospitals are doing in both areas.

PMID- 1398601
TI  - Hospitals find ways to integrate risk-management functions.
AB  - Hospitals that have successfully integrated the risk-management function with
      other hospital departments say that the process requires both education and
      teamwork. Among the major challenges: overcoming physician reluctance to
      participate in risk-management activities, and linking risk management to quality
      assurance.

PMID- 1398602
TI  - Hospitals begin to implement worker drug-testing programs.

PMID- 1398603
TI  - White House moving ahead on reform. Interview by Mark Hagland.

PMID- 1398604
TI  - Pharmacists work on pediatric dosage problems.

PMID- 1398605
TI  - Keeping patient data secure within hospitals.

PMID- 1398606
TI  - HMO contracting: how to minimize UR liability.

PMID- 1398607
TI  - Rochester: community rating = insurance access.
AB  - Despite opposition from some quarters, the New York State Legislature recently
      passed a small-group reform bill requiring community rating in health insurance
      throughout that state. The health care system of Rochester, NY, the author
      contends, proves that community rating is both good public policy and good
      business practice.

PMID- 1398608
TI  - Polymorphism and differential selection for the sexes.
AB  - Various genetic models with different fitnesses for the sexes are investigated.
      Only a limited set of fitness values will result in a stable polymorphism, and
      the rate of approach to these equilibrium frequencies is extremely slow. These
      results indicate that there are problems associated with the interpretation of
      some human genetic traits by such models.

PMID- 1398609
TI  - Inbreeding effects on reproductive outcome: a study based on a large sample from
      the endogamous Vadde of Kolleru Lake, Andhra Pradesh, India.
AB  - Inbreeding effects on reproductive outcome vis-a-vis fertility, prenatal loss and
      prereproductive mortality, and secondary sex ratio of live and dead children were
      examined in a large sample of 2078 women of the Vadde fishing population of
      Kolleru Lake in Andhra Pradesh, India. Demographically, this population is a
      single endogamous unit. By using an exponential regression model with the
      proportion of offspring survival as a dependent variable and the inbreeding
      coefficient as an independent variable, I further examined the inbreeding
      effects. The results were compared with results from other fishing groups and
      other southern Indian and non-Indian populations. The results among the Vadde
      were consistent with those found for other groups of Telugu-speaking fishermen
      and several other southern Indian populations in that the effects were neither
      perceptible nor significant. The average B value and the number of lethal
      equivalents found for the highly inbred southern Indian populations in general
      and for the Vadde in particular were much smaller than those from other parts of
      the world, providing empirical support to Sanghvi's hypothesis on long-term
      effects of inbreeding.

PMID- 1398610
TI  - Digital dermatoglyphic patterns of Eskimo and Amerindian populations:
      relationships between geographic, dermatoglyphic, genetic, and linguistic
      distances.
AB  - Dermatoglyphic traits have been used to assess population affinities and
      structure. Here, we describe the digital patterns of four Eskimo populations from
      Alaska: two Yupik-speaking villages from St. Lawrence Island and two Inupik
      groups presently residing on mainland Alaska. For a broader evolutionary
      perspective, these four Eskimo populations are compared to other Inuit groups, to
      North American Indian populations, and to Siberian aggregates. The genetic
      structures of 18 New and Old World populations were explored using R-matrix plots
      and Wright's FST values. The relationships between dermatoglyphic, blood genetic,
      geographic, and linguistic distances were assessed by comparing matrices through
      Mantel correlations and through partial and multiple correlations. Statistically
      significant relationships between dermatoglyphics and genetics, genetics and
      geography, and geography and language were revealed. In addition, significant
      correlations between dermatoglyphics and geography, with linguistic variation
      constant, were noted for females but not for males. These results attest to the
      usefulness of dermatoglyphics in resolving various evolutionary questions
      concerning normal human variation.

PMID- 1398611
TI  - Genetic and dermatoglyphic distances among Basque Valleys.
AB  - Palmar dermatoglyphics of a sample including 552 males and 701 females from 8
      Basque valleys were analyzed. We studied the frequency of palmar pattern types
      and compared them using correspondence the frequency of palmar pattern types and
      compared them using correspondence analysis. The results of this comparative
      study show that there is diversity among valleys and also that this diversity
      depends on the trait and on sex. Genetic drift could explain this variability
      found in the Basque population.

PMID- 1398612
TI  - Nonmetric tooth crown traits in the Ami tribe, Taiwan aborigines: comparisons
      with other east Asian populations.
AB  - The frequencies of occurrence of 17 tooth crown traits in the living Ami tribe,
      which inhabits the east coast of Taiwan, were investigated and compared with
      other East Asian populations based on Turner's (1987) Mongoloid dental variation
      theory. Principal coordinate analysis based on Smith's mean measure of divergence
      using frequencies of the 17 traits suggests that the Ami tribe together with the
      Yami tribe and the Bunun tribe is included in the sinodont group typical of the
      Chinese mainland and northeast Asia. In light of these results and the estimated
      distribution of sinodonty and sundadonty in the past and the present, we
      speculate that the gene flow from Chinese mainlanders to native sundadonts, who
      seem to have migrated northward to Taiwan, contributed significantly to the
      formation of the living Taiwan aboriginal groups, sinodonts. Among the aboriginal
      tribes of Taiwan, the Ami have characteristics intermediate between those of the
      Yami and the Bunun. The relative positions of these tribes in East Asian
      populations suggests that the extent of sinodontification and of genetic
      isolation is one of the causes of the intertribal variation.

PMID- 1398613
TI  - Rate of growth in length of Bangladeshi infants as a function of attained length.
AB  - We examine variation in the rate of growth in length of breast-feeding infants
      from rural Bangladesh. These data were collected between November 1985 and
      February 1986 from two rural sites. Eighty-eight infants, ranging from birth to 4
      months of age at the start of the study and their mothers were measured monthly
      for 4 months. Length increased linearly with age over this 4-month period
      (infants' average bias-adjusted R2 = 0.90). The relationship between infant rate
      of growth in length and attained length was analyzed by two different methods:
      Oldham's (1962) method of regressing rate of growth on mean length and
      Blomqvist's (1977) method of regressing rate of growth on estimated initial
      length. The methods gave similar results. The rate of growth was negatively
      associated with mean infant length over the 4-month period (p less than 0.001);
      that is, shorter infants grew at a faster rate than longer infants. For every
      centimeter shorter the infant was, the rate of growth was 0.1 cm/mo faster on
      average; the effect was greater among males than among females. The average rate
      of growth was greater for males than for females and greater in financially
      solvent households and varied by site. Infant growth rate was slower among older
      infants than among younger infants, as expected. However, after adjusting for
      mean infant length, age was no longer significantly associated with infant growth
      rate, although mean infant length remained highly significant. Forty-one percent
      of the variation in infant rate of growth in length was explained by mean infant
      length, sex, sex by length interaction, household financial solvency, and site.

PMID- 1398614
TI  - Short-term projections of AIDS cases in Mexico.
AB  - We attempt to analyze and predict the behavior of the AIDS epidemic in Mexico.
      The reporting delay is corrected by using a cluster analysis, and the corrected
      data are used to make short-term projections by extrapolation, by fitting linear
      and log-linear models, and by back-calculation. The incubation period is assumed
      to have a Weibull distribution, and step functions are used for the infection
      functions. Most of the methods predict a mean of 25,000 accumulated cases by the
      end of 1993, and a comparison of the predictions with actual data up to November
      1990 shows good agreement in all cases except the log-transformation linear
      model. The data for 1990 also show the reporting delay correction to be adequate
      in most cases.

PMID- 1398615
TI  - Y-chromosome-specific haplotypes of Jews detected by probes 49f and 49a.
AB  - A sample of Ashkenazic and Sephardic Jews has been studied with respect to
      haplotypes at the 49f-49a Y-specific DNA probes. Only seven haplotypes were found
      in Jews, three of them (VII, VIII, and XI) being the most widespread. Haplotype
      distribution in the European non-Jewish population is different.

PMID- 1398616
TI  - [Homology study of leptospires by molecular hybridization].
AB  - Nick translation and random primer labelling method were applied to prepare three
      genomic DNA probes from Leptospira interrogans strain 017, Leptospira biflexa
      strain Patoc I and Leptonema illini strain 3055, and then hybridized with DNA of
      17 strains leptospires from different genus, species, serogroup and serovar. The
      results showed no homology between Leptospira and Leptonema, and only a low
      degree of homology between L. interrogans and L. biflexa but it showed a high
      degree of homology among L. interrogans. The study also proved the possibility to
      establish a DNA probe prepared from a single leptospira strain to detect
      different serovars.

PMID- 1398617
TI  - [A mid-infrared spectra study of a series of benzocrown ether and macrocyclic
      polyether diester].
AB  - With a Nicolet 20 SX B Fourier Transform infrared spectrometer, the mid-infrared
      spectra in region of 4000-400 cm-1 were observed for a series of benzocrown ether
      and macrocyclic polyether diester. A difference in the wavelength of absorption
      of the ether bond was found between benzocrown ether and macrocyclic polyether
      diester. The wavelength of absorption of the ether bond of the compounds I-IV
      moved down about 25 cm-1, as compared with that of the compounds V-IX.

PMID- 1398618
TI  - [Solid phase clean-up and determination of vesnarinone in plasma by high
      performance liquid chromatography].
AB  - Vesnarinone, a new positive inotropic agent, was synthesized by Tominaga et al of
      the Otsuka Pharmaceutical Co. Ltd. Institute in 1982. Determination of
      Vesnarinone plasma level in dogs by reversed-phase HPLC was developed and
      presented in this paper. A plasma sample preparation was carried out by solid
      phase cleaned-up through neutral aluminum column (10 x 1 cm I.D.) eluting with
      methanol. The chromatography consisted of a slim-pack CLC ODS column (150 x 6.0
      mm I.D.) with methanol: 1 mmol/L HAc (55:45) as the mobile phase at a flow rate
      of 0.8 ml/min. Spectrophotometric detection was at 271 nm, and column temperature
      was at 25 degrees C. Using 3,4-dihydro-6-(4-(4-methoxybenzoyl)-1-piperazinyl)-2
      (1H) quinolinone as an internal standard. The cleaned-up procedure is simple,
      rapid and satisfactory. The detection limit of vesnarinone was 0.5 ng/ml (R/N,
      3:1). The calibration curve was liner (r = 0.99998) in the concentration range of
      5-500 ng/10 microliters. Within-day and day-to-day precisions (CV%) were 1.56 and
      1.98. The recoveries obtained from cleaned-up and spiked plasma samples were up
      to 86.52 +/- 2.77% and 96.26 +/- 5.46%, respectively.

PMID- 1398619
TI  - [Preparation of a new tissue-based biosensor].
AB  - A new adenosine electrode using rabbit thymus tissue as catalyst is described.
      The tissue membrane was immobilized at the surface of an ammonia gassensing
      electrode for determination of adenosine in body fluid or tissue samples. This
      tissue-based biosensor showed excellent selectivity, and sensitivity, with a
      response slope of 51.2mV/decade, linear range of 3.16 x 10(-5)-5.62 x 10(-3)
      mol/L, coefficients of variation ranging from 1% to 5.72% (n = 7, m = 5),
      recoveries of adenosine in rabbit blood from 94.9% to 108.4% (n = 5, m = 5), and
      response time of 7 min. The life-time of the electrode was 25 days and 14
      analogous compounds showed no significant interference.

PMID- 1398620
TI  - [Plasmid analysis and antibiotic resistance pattern measurement of Shigella in
      Chengdu].
AB  - A total of 81 strains of Shigella isolated from sporadic cases and cases in an
      outbreak of Shigella sonnei infection was analysed by plasmid profiles and
      antibiotic resistance patterns. The strains had a high resistance patterns. The
      strains had a high resistance of ampicillin, tetracycline, trimethoprim
      sulfamethoxazole and chloramphenicol; while 97.2% of the strains were susceptible
      to gentamicin, kanamycin. The results showed that 50% of the strains harbored
      plasmid patterns within each species, which indicated that many genetically
      different strains of Shigella were responsible for dysentery epidemics in
      Chengdu. According to the results of the plasmid analysis and antibiotic
      resistance pattern measurement made in the outbreak strains, it was clearly seen
      that most of the strains were similar or fundamentally similar, which suggested
      that one or two strains with genetical homology were the main causative agent for
      the outbreak. We think that plasmid profiles and antibiotic resistance patterns
      are applicable to the identification of the outbreak strains of dysentery as an
      efficient epidemiologic tool.

PMID- 1398621
TI  - [Biochemical studies of the temporomandibular ligament in dogs].
AB  - The purpose of this investigation was to determine the biochemical composition of
      the normal adult dog's temporomandibular ligament (TML) along its ligament (TML)
      along its length. Water content and hexosamine concentration as an index of
      glycosaminoglycan content and collagen concentration were quantified; and the
      results compared statistically with anatomically identified TML segments. The TML
      contained lower water content and higher collagen, hexosamine concentration than
      capsule (P less than 0.05). All the contents of these components in different
      locations along the ligament were not significantly different, with the exception
      that on the insertion site of the temporal eminence the concentration of the
      hexosamine was less than that in other areas (P less than 0.05). This study
      provided useful data for the analysis of TML functions and its mechanical
      properties.

PMID- 1398622
TI  - [Technique of measuring esophageal pressure in rabbits and its application to
      measurement of pulmonary compliance and resistance].
AB  - Esophageal pressure (Pes) was measured under non-invasive condition by an
      esophageal balloon made by ourselves, and the optimal position of rabbits for
      measuring Pes was explored. The correspondence between Pes and pleural pressure
      (Ppl) was examined in rabbits during different depths of breathing with varied
      lengths of balloon and varied depths of insertion of balloon into the esophagus.
      The results showed that the amplitude of Pes only on supine position was higher
      than that on the left and right lateral and prone positions, but no significant
      difference was noticed among the 3 positions. The optimal balloon length was 4-6
      cm. The optimal depth of insertion of balloon into the esophagus was 20 cm. The
      pulmonary dynamic compliance and pulmonary resistance were measured in 11 white
      rabbits with 5 cm balloon, 20 cm depth of insertion, on the left lateral
      position. The results were correspondent with other authors. No significant
      difference was noticed in repeated measurements on 8 of the 11 rabbits 5 days
      later.

PMID- 1398623
TI  - [Study on variation of plasma gamma-aminobutyric acid concentration in rat model
      of hepatic encephalopathy due to fulminant hepatic failure].
AB  - The plasma gamma-aminobutyric acid (GABA) concentration was measured by a radio
      receptor assay in rat model of hepatic encephalopathy due to fulminant hepatic
      failure (FHF) induced by intraperitoneal injection of D-galactosamine (GalN). The
      results showed that, in FHF group, the plasma GABA increased parallelly with the
      degree of hepatic encephalopathy after GalN i.p. (r = 0.944, P less than 0.05).
      In about 48 h, mean plasma GABA concentration was elevated nearly 8-fold. These
      findings suggest that, in liver failure, elevated plasma GABA concentration may
      play a role in the pathogenesis of hepatic encephalopathy.

PMID- 1398624
TI  - [A preliminary study of the chord and specific time constants in 342 healthy
      children].
AB  - Using Knudson's method, the chord time constant, tau ch, tau ch75, tau ch50, tau
      ch25, and specific time constant, S tau, 1/V75, 1/V50, 1/V25, at high, middle and
      low lung volumes were calculated from V75, V50 and V25 of the MEFV curves
      measured previously from 342 healthy children of 3-6 years of age in a nursery.
      The multiple stepwise regression equation were built with age, height and FVC as
      independent variables by the IBM-XT/PC computer. The result showed that the S tau
      corrected by volume from tau ch could reflect the time required for change of
      unit lung volume more precisely than tau ch owing to the elimination of the
      influence of lung volume. The S tau was shortened with the increase of age, and
      was negatively correlate with age and FVC. These facts reflected the growth of
      lung elastic pressure (PLel) and airway conductance (Gaw) with the increase of
      age. The prolongation of S tau with the decay of lung volume just reflected the
      decrease of PLel and Gaw with the decay of lung volume. No regular changes of tau
      h were observed with age and lung volume. Probably, it was concerned with the
      complexity of factors affecting the tau ch.

PMID- 1398625
TI  - [Observation of monoclonal antibody E4B7D5 inhibitory effect on leptospiral
      adherence using scanning electron microscope].
AB  - BALB/c mice were immunized intraperitoneally with outer envelopes of serogroup
      icterohaemorrhagiae lai serovar strain 017 leptospires. Monoclonal antibody
      (McAb) E4B7D5 against outer envelopes (IgG1, agglutinating titre 1:25,600) was
      produced by hybridoma technique. Passive immunoprotection experiments have
      demonstrated the immunoprotection of McAb E4B7D5 against strain 017 leptospires.
      Effect of McAb E4B7D5 on leptospiral adherence to the surface of normal human
      pulmonary embryonic fibroblasts was observed by using scanning electron
      microscope. The results indicated that the leptospiral adherence noted in various
      agglutinating titre McAb E4B7D5 groups was less frequent than that in the three
      control groups. It was concluded that the inhibitory effect of McAb E4B7D5 on
      leptospiral adherence may play a role in the immunoprotection.

PMID- 1398626
TI  - [Effects of tian-ma injection on myocardial ischemia and lipid peroxidation in
      rabbits].
AB  - Lipid peroxidation initiated by oxygen free radicals played an important role in
      the pathogenesis of coronary heart disease. The purpose of this study was to
      explore the effects of Tian-Ma (Gastrodia elata Bl.) injection on myocardial
      infarct size and lipid peroxidation by observing serum malondialdehyde (MDA)
      levels. Twenty-six New Zealand rabbits were divided into control group (n = 6),
      ischemic group (n = 10), and Tian-Ma treated group (n = 10). Left ventricular
      branch (LVB) of coronary artery was ligated at its middle third in ischemic and
      treated groups. LVB was not ligated in control group. Tian-Ma injection was given
      intravenously (1 mg/kg) every 8 hours after ligation in treated group for 48
      hours. Precordial 12-lead ECG mapping was recorded before operation and at 3, 24
      and 48 hours after occlusion. Hemodynamic changes (HR, LVP) were monitored before
      and 0.5, 3 and 48 hours after ligation. Serum MDA levels were determined by
      thiobarbituric acid spectrophotometry before operation, and 0.5, 3, 9, 24, and 48
      hours after ligation. Dual staining technique was used 48 hours after ligation to
      determine the area at risk and infarct size. The results showed that Tian-Ma
      injection did not decrease sigma ST elevation (P greater than 0.05), but NQ was
      significantly lower during ischemia in treated group (P less than 0.01), Tian-Ma
      injection reduced the area at risk by 23.5% (P less than 0.05) and infarct size
      by 34.5% (P less than 0.01). Tian-Ma injection significantly decreased the levels
      of serum MDA 24 and 48 hours after occlusion (P less than 0.01).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1398627
TI  - [Detection of G2m(n) factor in bloodstains using ELISA inhibition test].
AB  - For the purpose of detecting G2m(n) factor in human bloodstains, an ELISA
      inhibition test using mouse antihuman G2m(n) monoclonal antibody was established.
      The results revealed that the correctness rate for G2m(n) factor detection was
      100%. The minimal amount of bloodstain required for detecting G2m(n) factor was
      0.25 cm x 0.125 cm. This approach provided a new method for individual
      identification of human bloodstains.

PMID- 1398629
TI  - [Study of the estrogen receptor and progesterone receptor in human cervical
      carcinoma].
AB  - Three hundred and twelve different cervical specimens have been tested for
      estrogen (ER) and progesterone receptor (PR) content with dextran-coated charcoal
      method (DCC). The results showed that the concentrations of ER and PR in normal
      cervical tissues were higher than those in malignant cervical tissues, and that
      the percentage of positive scores for ER and PR in cervical squamous epithelial
      tissues were higher than that in malignant cervical tissues. That the variances
      of ER and PR in cervical malignant tumors were not parallel suggested that the
      production or/and the mechanism of receptor action might be impaired. The
      percentage of positive scores for ER was not correlated with the clinical stages
      whereas that of PR was inversely proportional to clinical stages. That some
      patient with cervical cancer had high level of PR and had both ER and PR positive
      implied the possibility for endocrine therapy. The content and distribution of ER
      and PR in normal cervical tissues are consistent with the effects of sex hormone.

PMID- 1398628
TI  - [Clinical significance on expression of the ras gene product P21 in human
      cervical carcinoma tissues].
AB  - Using MAB-P21 as a probe, the expression of gene product was studied by
      immunohistochemical ABC method, ABC staining of gel electrophoresis and ELISA
      quantitative analysis. The expression of P21 was detected in 107 cases of uterine
      cervix tissues, among which 70 were cervical carcinoma, 30 were chronic
      cervicitis and 7 normal cervix. Experimental results showed that obviously
      positive expression was noted in the specimens of cervical carcinoma and its
      positive rate was 72.8% (51/70). It was observed that the expression of P21
      varied with grades of cell differentiation in cervical carcinoma. The level of
      P21 expression in high differentiated type was higher than that of the middle and
      low differentiated types. On the contrary, there was no detectable ras P21 in the
      normal cervix tissue and only 2 cases of cervicitis expressed positively (2/30).
      The results of ABC staining of electrophoresis showed that there was a P21
      special staining band in cervical carcinoma tissues. And the contents of P21
      protein were higher in cervical carcinoma than in normal cervix and cervicitis (t
      test, P less than 0.001). The expression of P21 was considerably enhanced in
      malignant tissue as compared with that in benign lesion.

PMID- 1398630
TI  - [Estrogen and progesterone receptors in laryngeal carcinoma].
AB  - The existence of hormone receptors on or within neoplastic tissue has potential
      diagnostic, therapeutic, and prognostic importance. It has now been demonstrated
      in many reports that cancers of the breast and prostate often express hormone
      receptors and can be controlled by hormone manipulation. The fact that larynx is
      a target organ for androgenic steroids has long been known. The question of
      whether laryngeal carcinoma expresses hormone receptors has been a matter of
      interest. We adopted the fluorescent hormone conjugate method to measure the
      estrogen receptor (ER) and progesterone receptor (PR) in 25 patients with
      laryngeal cancer. Our findings indicated that in 25 samples of laryngeal cancer
      48% were ER positive, and 68% were PR positive. Cells of the laryngeal cancer not
      only contain ER and PR but also have relationship between the presence of
      receptors and the degree of histologic differentiation. Low differentiated
      cancers are inclinable to contain low level receptors. From this initial survey
      it appears that the hormone receptors could play an important role in the cancer
      of larynx. The presence of receptors in some laryngeal carcinoma implicates that
      these tumors are possibly hormone sensitive.

PMID- 1398631
TI  - [Study of quantitative diagnosis of cerebral arteriosclerosis].
AB  - On the basis of clinical diagnostic criterion of cerebral arteriosclerosis, we
      selected, 72 patients with cerebral arteriosclerosis, 72 patients with suspected
      cerebral arteriosclerosis and 70 healthy individuals and screened 42 variables
      obtained from clinical and accessory examination with a stepwise discriminant
      analysis and a stepwise regression analysis. Finally we performed a logistic
      discriminant analysis of 15 selected variables in order to establish diagnostic
      discriminant formulas, Ya and Yc. It was found that a diagnostic coincidence rate
      for rediscriminant analysis of 212 individuals with the formulas was 100%. Very
      high sensitivity (96.7%), specificity (100%), positive predicted value (100%),
      negative predicted value (83.3%) and accuracy (97.1%) were noted in a prospective
      double-blind test on 34 subjects. The authors suggest that the discriminant
      formulas Ya and Yc established for diagnosis of cerebral arteriosclerosis be
      widely applicated.

PMID- 1398632
TI  - [Relationship between height, collagen metabolism, hair zinc and excessive
      fluoride intake].
AB  - After eliminating confounding factors, the study was made on the relationship
      between height, collagen metabolism, hair zinc and excessive fluoride intake. 140
      schoolchildren aged 12-13 years born and reared in endemic fluorosis areas were
      surveyed. The results were as follows: 1. The average height of children with
      dental fluorosis III degree (DF III degree) was appreciably smaller than that of
      children without dental fluorosis. Among children with excessive fluoride intake,
      a negative correlation between the height and fluoride level in staple foods was
      seen. 2. The more the fluoride ingested, the higher the urinary THP excreted,
      showing that fluoride intoxication interfered with the collagen metabolism. 3.
      Among children with excessive fluoride intake, the height showed negative
      correlation with urinary THP/Cr, suggesting that the effect of fluoride on
      collagen metabolism indicated the mechanism of height retardation. 4. As compared
      to control group with the excessive fluoride intake but without dental fluorosis
      group, there was a significant reduction in hair zinc in group with DF III
      degree, suggesting that the zinc in the body decreased because of zinc metabolism
      disturbance by excessive fluoride intake. But among cases with excessive fluoride
      intake, no appreciable correlation between hair zinc and height was found.
      Therefore, it could not be confirmed that the effect of fluoride on zinc
      metabolism affected the height development.

PMID- 1398634
TI  - [The expression of oncogenes in the development of human brain].
AB  - Seven oncogenes (c-myc, L-myc, N-myc, v-erbB, c-fos, Ha-ras and mos) were used as
      the probe to detect the total RNA of every part (cerebellum, temporal folium,
      frontal folium and occipital folium) in human brain from 2 cases of 6 mon fetus
      and the total RNA in fetal development (4 mon, 5 mon, 6 mon, 7 mon, and newborn)
      of human brain tissue by RNA dot hybridization analysis. The results showed that
      most oncogenes were expressed at high level in cerebellum and occipital folium of
      6 mon fetus and at low level in temporal folium; there was similar expression of
      c-myc, L-myc and N-myc in fetal development of human brain tissue, and the
      highest level was in the 5 mon fetal brain. There was no expression of erbB gene
      in normal human brain. The high level expression of Ha-ras and c-fos genes was in
      the middle and later stages of fetal development. These results suggested that c
      myc, L-myc, N-myc, erbB, Ha-ras, c-fos and mos genes might play an important role
      in the fetal development of human brain.

PMID- 1398633
TI  - [Relationship among dosages of aminophylline, plasma levels of theophylline and
      variation of pulmonary arterial pressure].
AB  - The relationship among the dosages of aminophylline, plasma levels of
      theophylline and variations of mean pulmonary arterial pressure (mPAP) in 72
      patients with COPD was investigated. The results showed that after a different
      loading dosage of aminophylline (6 mg/kg, 5 mg/kg and 4 mg/kg) was administered
      by intravenous injection, mPAP in the 6 mg/kg group was decreased more
      significantly (P less than 0.01) than that in the 4 mg/kg group. In the 6 mg/kg
      group, the decreased mPAP period sustained for 120 min, which was longer than
      that in the other 2 groups. The plasma levels of theophylline in the 6 mg/kg
      group of patients 30 to 120 min after loading dose injected were 115.54-79.04
      mumol/L, which were higher than that in the others. Within the 120 min period of
      observation after the drug was administered no patients in any of these groups
      showed severe untoward effects. According to the results of this experiment, we
      suggest that the 6 mg/kg as a loading dose should be advised for the treatment of
      pulmonary hypertension in COPD. The optimum time to give the maintenance dosage
      should be set within 2 h after the loading dose. It is necessary to monitor the
      plasma levels of theophylline while aminophylline is administered, so that
      optimal therapeutic effects could be achieved without side effects.

PMID- 1398635
TI  - [Plasma fibronectin determination in acute bacterial pneumonia].
AB  - Plasma fibronectin (PFn) level was measured with immunoelectrophoresis in 40
      healthy adults and 30 patients with acute bacterial pneumonia. The results showed
      that PFn was considerably lowered in acute bacterial pneumonia (214.49 +/- 77.84
      micrograms/ml) when compared with that of healthy controls (292.48 +/- 43.11
      micrograms/ml), (P less than 0.001). In the pneumonia group (10 severe cases) the
      level of PFn was significantly lowered than that in the moderate or mild cases
      (127.45 +/- 31.03 micrograms/ml vs. 255.11 +/- 54.16 micrograms/ml), (P less than
      0.001). In 11 cases of recovering pneumonia, PFn was significantly higher than
      that in exacerbation period (213.13 +/- 41.32 micrograms/ml vs. 154.52 +/- 51.27
      micrograms/ml) (P less than 0.001). We think that PFn level is helpful to
      evaluate the clinical course and prognosis of acute bacterial pneumonia.

PMID- 1398636
TI  - [The variations of PRL, LH, FSH and testosterone in renal disease].
AB  - Blood PRL was measured with RIA in 22 males and 19 females with various degrees
      of renal insufficiency. At the same time, blood LH, FSH, testosterone were
      studied in all the male patients and 20 sex-age matched healthy subjects. The
      results showed that the levels of PRL and LH were increased, and the level of
      testosterone was decreased significantly in male uremic patients. There was a
      significant negative correlation between PRL and testosterone. All the above
      parameters were measured again 8-25 days after continuous ambulatory peritoneal
      dialysis (CAPD) therapy in 5 male uremic patients. The BUN and Cr levels
      decreased and the clinical manifestations of uremia improved, but the levels of
      PRL, LH, FSH and testosterone showed no significant changes. The mechanisms of
      these variations were discussed.

PMID- 1398637
TI  - [The antigastroulcerative activity of beta-sitosterol-beta-D-glucoside and its
      aglycone in rats].
AB  - Beta-sitosterol-beta-D-glucoside and its aglycone (the major constituent of the
      seed oil of Hippophae rhamnoides L.) were investigated for their
      antigastroulcerative activity in rats. Two experimental gastric ulcer models were
      selected: chronic acetic acid-induced ulcers and cold stress-induced ulcers. Both
      the glucoside and its aglycone showed antiulcerative activity in chronic acetic
      acid-induced gastric ulcer models, and their effects were at least comparable to
      the effects of wishupin in combination with cimetidine. The effect of aglycone
      appears better than the glucoside's. Glucoside also showed visibly antiulcerative
      effects on cold stress-induced ulcers, but wishupin combined with cimetidine did
      not have such effects.

PMID- 1398638
TI  - Environmental pathology: the pathologist's responsibility?

PMID- 1398639
TI  - Slateworker's pneumoconiosis.
AB  - Slate is a metamorphic rock comprising silica, aluminum silicates, and small
      amounts of chlorite, hematite, magnetite, and various carbonates. In the United
      States slate is quarried in Virginia, Pennsylvania, New York, and Vermont.
      Workers are exposed during mining and processing of the slate and in crushing
      mills that prepare gravel. We have conducted detailed mineralogic and pathologic
      studies on the lungs of 12 workers who developed a pneumoconiosis while employed
      in the quarries of west central Vermont and adjacent areas of New York.
      Perivascular and peribronchial lesions accompanied by interstitial fibrosis and
      macules were scattered diffusely in the lungs. The lesions were associated with a
      variable number of silicotic nodules. Scanning electron microscopy combined with
      energy-dispersive x-ray spectrometry demonstrated aluminum and silicon-containing
      particles with variable cationic constituents and silicon alone in a pattern
      typical of free crystalline quartz. By x-ray diffraction analysis the majority of
      the mineral particulates were free crystalline quartz and muscovite, an aluminum
      silicate in the mica group of minerals. Slateworkers are exposed to respirable
      airborne dust that has the capacity to produce a pneumoconiosis that differs from
      classic silicosis.

PMID- 1398640
TI  - Neuropathology of the spinal cord in the acquired immunodeficiency syndrome.
AB  - The neuropathologic findings in the spinal cord were reviewed in 138 consecutive
      autopsies of patients with the acquired immunodeficiency syndrome. In all cases
      both the brain and spinal cord were examined by conventional histologic
      techniques, and in 63 cases immunohistochemistry was used to detect human
      immunodeficiency virus (HIV), Toxoplasma gondii, cytomegalovirus, and JC
      papovavirus antigens. The most common observation was a normal spinal cord (60%).
      Vacuolar myelopathy (VM) was observed in 23 (17%) cases. Human immunodeficiency
      virus myelitis was evident in 8% of cases. Human immunodeficiency virus myelitis
      was associated with HIV encephalitis in 65% of the cases. Opportunistic
      infections of the spinal cord were uncommon, consisting of cryptococcosis (five
      cases), cytomegalovirus (four cases), toxoplasmosis (one case), and progressive
      multifocal leukoencephalopathy (one case), and almost always were seen with
      cerebral and/or systemic infection by these agents. Malignant lymphoma rarely
      involved the spinal cord (four cases); all were B-cell lymphomas and were
      associated with cerebral and/or systemic lymphoma. Other abnormalities rarely
      observed were Wallerian degeneration of the corticospinal tracts or posterior
      columns (6%) and focal microinfarcts. Most cases of VM (78%) were not associated
      with HIV myelitis, and in the five patients with both VM and HIV myelitis, HIV
      infected cells were not found in the regions affected by VM. In contrast, 65% of
      cases with VM were associated with HIV encephalitis. The pathogenesis of VM
      remains unknown; it is probably not due to direct infection by HIV.

PMID- 1398641
TI  - Nodular lymphocyte-predominant Hodgkin's disease: study of immunoglobulin light
      chain protein and mRNA expression.
AB  - The techniques of immunohistochemistry and in situ hybridization were applied to
      10 formalin- or B5-fixed, paraffin-embedded cases of nodular lymphocyte
      predominant Hodgkin's disease to determine whether lymphohistiocytic (L&H) cells
      contain any detectable amount of immunoglobulin light chain protein or messenger
      RNA. None of the cases studied demonstrated any detectable amount of either kappa
      or lambda light chain mRNA within L&H cells or Reed-Sternberg cells despite
      positive labeling of plasma cells, immunoblasts, and germinal center cells.
      Polyclonal kappa light chain antibody studies showed positive staining of L&H
      cells in seven cases, including three costaining with polyclonal lambda light
      chain antibody. Monoclonal kappa and lambda light chain antibody studies,
      however, showed no staining of L&H cells despite positive staining of
      immunoblasts and plasma cells. It is suggested that L&H cells do not synthesize
      appreciable amounts of light chain immunoglobulin protein and are not closely
      related to reactive immunoblasts or germinal center cells.

PMID- 1398642
TI  - Cardiac histologic pathology characteristic of trisomies 13 and 21.
AB  - To identify fetal histologic features characteristic of specific chromosomal
      anomalies, we reviewed histologic slides of 415 cases, including therapeutic and
      spontaneous abortuses, stillbirths, and perinatal deaths. These included 126
      cases (30%) with karyotypically confirmed trisomy 21 and 23 cases (5.5%) with
      trisomy 13. Two histologic abnormalities of the fetal heart were identified that
      correlated with specific karyotypic abnormalities: (1) a discrete central
      papillary muscle calcification was present in 14 of 85 (16%) cases with trisomy
      21, in seven of 18 (39%) cases with trisomy 13, and in six of 255 (2%) controls
      (P less than .001); and (2) a focal ventricular epicardial lymphocytic infiltrate
      was present in 22 of 93 (24%) cases with trisomy 21 versus nine of 284 (3%)
      controls (P less than .001). When both histologic abnormalities coexisted,
      trisomy 21 was present in five of six cases (83%). Neither histologic finding was
      significantly associated with fetal or maternal infection or congenital heart
      defects. In a restricted prospective study of the hearts of fetuses with trisomy
      21, papillary muscle calcification was demonstrated by specimen radiographs in
      four of six (67%) cases; one case was studied by specimen ultrasonogram, which
      identified a papillary muscle echodensity. We conclude that (1) a focal
      ventricular epicardial lymphocytic infiltrate is characteristic of trisomy 21,
      (2) papillary muscle microcalcifications are characteristic of trisomies 13 and
      21, and (3) further studies are needed to determine whether papillary muscle
      calcification might be useful in antenatal ultrasonographic screening for
      chromosomal anomalies.

PMID- 1398644
TI  - Pleomorphic variant of invasive lobular carcinoma of the breast.
AB  - Infiltrating lobular carcinoma (ILC) of the classic type is well recognized; less
      well appreciated is a group of variant forms of ILC, which includes solid,
      alveolar, mixed, apocrine, signet-ring, histiocytoid, and tubulolobular variants.
      In addition, Page et al (Diagnostic Histopathology of the Breast, Churchill
      Livingstone, 1987, pp 219-226) recently have emphasized the pleomorphic variant
      of ILC, which demonstrates the infiltrating pattern of classic ILC; however, the
      nuclei are more pleomorphic and have features that may overlap with those of
      infiltrating duct carcinoma. To determine whether pleomorphic ILC shows
      significant prognostic differences from classic ILC, we reviewed the clinical
      courses of 25 patients with classic ILC and compared them with 16 patients with
      pleomorphic ILC. The major determinant in placing ILC into the pleomorphic
      category was the presence of nuclei of nuclear grade 2 or 3. All classic ILCs had
      nuclei of grade 1 by the Scarff-Bloom-Richardson criteria. Survival to recurrence
      was significantly worse (P less than or equal to .05) for the patients with
      pleomorphic ILC at lengths of survival greater than 30 months. In addition, node
      negative patients with pleomorphic ILC were four times more likely to experience
      recurrence than node-negative patients with classic ILC; those with positive
      nodes and pleomorphic histology were 30 times more likely to experience
      recurrence. Although there appeared to be a trend toward decreased overall length
      of survival for those patients with pleomorphic ILC when compared with patients
      with classic ILC, this difference was not statistically significant.

PMID- 1398643
TI  - The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and
      review of Japanese Autopsy Registry Data.
AB  - We present pathologic findings for 52 livers (51 autopsy specimens and one wedge
      biopsy specimen) from patients with systemic lupus erythematosus (SLE). Hepatic
      congestion was the most common disease (40 livers), followed by fatty liver (38),
      arteritis (11), cholestasis (nine), peliosis hepatis (six), chronic persistent
      hepatitis (six), nonspecific reactive hepatitis (five), cholangiolitis (four),
      nodular regenerative hyperplasia of the liver (three), and hemangioma (three).
      The data obtained here suggest that arteritis of the SLE liver is more common
      than has been recognized previously. One patient had hepatic infarction
      complications induced by arteritis. On the basis of the findings in the present
      study and a review of the literature, we suggest that hepatic infarction
      resulting from arteritis is rare in SLE. On the other hand, while occurrence of
      nodular regenerative hyperplasia of the liver in SLE patients has been considered
      to be rare, our findings suggest that it may be more common than has been
      recognized previously. Although congestion and cholestasis may be acute terminal
      illnesses, fatty change is considered to be specific to the SLE liver.
      Statistical analysis indicates that exposure to a large dosage of glucocorticoids
      is a significant factor in the etiology of severe fatty liver. In addition, our
      review of Japanese autopsy registry data for 1,468 patients with SLE indicates
      that the incidence of chronic liver diseases in SLE autopsy cases is as follows:
      chronic hepatitis, 2.4%; cirrhosis, 1.1%; and liver fibrosis, 0.8%.

PMID- 1398645
TI  - Graft eosinophilia in lung transplantation.
AB  - Graft eosinophilia was observed in lung biopsies from nine patients who received
      lung allografts. Five cases were associated with moderate to severe acute
      cellular rejection and responded well to steroid therapy. In this group the
      eosinophilia occurred early after transplantation and was associated with an
      elevated white blood cell count and occasional peripheral blood (one of five
      cases) and bronchoalveolar lavage (one of five cases) eosinophilia. A second
      group of four patients had graft eosinophilia due to infectious agents. In these
      cases patients frequently had underlying bronchiolitis obliterans (two of four
      cases) and developed tissue eosinophilia late after transplantation.
      Bronchoalveolar lavage cell profiles often demonstrated dramatic eosinophilia.
      Histologically, the biopsy specimens displayed an acute eosinophilic pneumonia,
      which was attributed to Aspergillus sp (two cases), coxsackie A2 virus (one
      case), and Pseudomonas maltophilia (one case). Two patients in this group died
      from infection. While eosinophils are a frequent cellular component of acute
      rejection reactions, they also may be the dominant cellular component in graft
      infection.

PMID- 1398646
TI  - Lectin-binding profile of plasmacytoid monocytes.
AB  - The lectin-binding profile of plasmacytoid monocytes, also known as plasmacytoid
      T cells, was studied in 18 axillary lymph nodes draining invasive breast
      carcinomas. The plasmacytoid monocytes bound fluorescein-conjugated lectins from
      Canavalia ensiformis (Con A), Phaseolus vulgaris (PHA-L), Arachis hypogaea (PNA),
      Ricinus communis (RCA I and II), and Triticum vulgaris (WGA), but no reaction was
      found with those from Dolichos biflorus (DBA) and Ulex europaeus (UEA I).
      Fluorescence was bright and the reactivity was distributed in a granular pattern
      in the cytoplasm of plasmacytoid monocytes, a staining pattern similar to that of
      monocytes and macrophages. B and T lymphocytes usually exhibited weak staining
      with the same lectins, and this was limited to the cell membrane. Plasmacytoid
      monocytes were originally thought to be closely related to the T-cell system. The
      results of recent immunocytologic studies and the lectin-binding profile of
      plasmacytoid monocytes observed in this study, however, suggest that these cells
      are related to the mononuclear phagocytic system.

PMID- 1398647
TI  - Anomalous right coronary artery associated with sudden death: an example of a
      neural crest migration defect.
AB  - A unique right coronary artery anomaly of hemodynamic significance was discovered
      in a young adult who suddenly died. In addition, abnormally migrated, or
      supernumerary, thymic tissue with embedded parathyroid glands was present. This
      combination of congenital malformations suggests that the pathogenesis of this
      rare cardiac anomaly may be explained by a cranial neural crest defect.

PMID- 1398648
TI  - Primary large cell lymphoma of the splenic sinuses: a variant of angiotropic B
      cell lymphoma (neoplastic angioendotheliomatosis)?
AB  - A case of large cell lymphoma of B-cell lineage originating in the splenic
      sinuses is described. In addition to widening the spectrum of primary malignant
      lymphomas of the spleen, this case raises the possibility that variants of
      angiotropic large cell lymphomas may exist that do not involve blood vessels but
      do involve the spleen and lymph node sinuses.

PMID- 1398649
TI  - Adrenocortical blastoma.
AB  - We report a previously undescribed virilizing malignant adrenocortical tumor in
      an 21-month-old infant with elevated serum alphafetoprotein. The tumor consists
      of a peculiar mixture of immature epithelial and mesenchymal elements as well as
      slit-like spaces partially lined by primitive epithelial cells. Focally, the
      tumor has features reminiscent of the normal embryologic development of the
      adrenal cortex. A panel of immunohistochemical stains revealed only vimentin
      reactivity. We propose the term "adrenocortical blastoma" for this unusual
      neoplasm.

PMID- 1398650
TI  - Benign lymphocytic angiitis and granulomatosis: a T-cell lymphoma?
AB  - Benign lymphocytic angiitis and granulomatosis is a T-cell lymphoproliferative
      disorder confined to the lung and corresponding to a low-grade angiocentric
      immunoproliferative lesion. Controversy remains as to whether these lesions are
      lymphomas. We report such a case in an 8-year-old patient with Burkitt's lymphoma
      in remission who presented with persistent bronchopneumopathy and bilateral
      pulmonary infiltrates on tomodensitometry. Surgical resection revealed the
      histologic changes of benign lymphocytic angiitis and granulomatosis.
      Immunohistochemistry showed no aberrant pan T-cell marker loss. Genetic analysis
      of frozen tissue by Southern blot DNA hybridization with probes to T-cell
      receptor beta- and gamma-chain genes and to the immunoglobulin heavy chain
      joining region gene (JH) identified no clonal rearrangement. Search for Epstein
      Barr virus-DNA sequences by in situ hybridization and Southern blot analysis
      provided negative results. Our data imply that lowgrade angiocentric
      immunoproliferative lesions are not exclusively lymphomas but might represent a
      borderline lymphoproliferative disease (seen in the course of many diseases),
      perhaps corresponding to host immune response.

PMID- 1398651
TI  - Adenocarcinoma of the prostate: diagnostic techniques.

PMID- 1398652
TI  - Clinical audit in genitourinary medicine "why, who, what, how and when?".

PMID- 1398653
TI  - "The health of the nation": a challenge for genitourinary medicine.

PMID- 1398655
TI  - Factors associated with genital chlamydial and gonococcal infection in females.
AB  - BACKGROUND: Predictors of chlamydia and gonorrhoea can be used to increase the
      cost-effectiveness and acceptability of screening programmes, and allow targeting
      of control strategies. METHODS: All women attending an STD clinic in 1988-1990
      were offered screening for chlamydia and gonorrhoea, and the test results
      correlated with a wide range of potential predictors using multiple logistic
      regression. RESULTS: Of 4822 attenders, 3533 (73.3%) were tested for chlamydia
      over a total of 5430 episodes, yielding 348 (6.4%) positives, and 3510 (72.8%)
      were tested for gonorrhoea over a total of 5450 episodes, yielding 100 (1.0%)
      positives. Independent predictors of chlamydial infection were being an STD
      contact, having endocervical gonorrhoea, being under 25, not having genital
      herpes, being Aboriginal, using oral contraception, not having a steady partner
      and having vaginal discharge or dysuria. For gonorrhoea such predictors were
      being Aboriginal, an STD contact, under 25, tattooed, having vaginal discharge or
      dysuria, and having had sex outside the state in the past three months. Selective
      screening criteria for gonorrhoea provided 91% of positives, eliminated the need
      for 42% of tests and resulted in an increased yield ratio of 1.5 whereas the
      corresponding outcomes for screening criteria for chlamydia were 91%, 29% and
      1.3, respectively. CONCLUSIONS: The diversity of STD epidemiology requires
      development of empirical screening guidelines for diverse settings.
      Standardisation of methodology to facilitate comparisons and extrapolation should
      include investigation of a wide range of variables, available before patient
      examination, by multivariate analysis, and choice of selective criteria to cover
      at least 90% of the infected population as well as resulting in a substantially
      increased yield (preferably an increased yield ratio of at least 1.5).

PMID- 1398654
TI  - Chlamydia trachomatis and oral contraceptive use: a quantitative review.
AB  - OBJECTIVES: Chlamydia trachomatis is now recognised as a major sexually
      transmitted disease; oral contraceptive use is rapidly increasing particularly in
      developing countries. There are thus important public health implications of the
      many reports that isolation of C trachomatis is more frequent among users of oral
      contraceptives. The aim of this analysis was to assess the strength and
      consistency of this association by summarising published studies between 1972 and
      1990. DESIGN: Studies identified were grouped according to whether they were
      prospective or case-control studies. Data were extracted and pooled estimates of
      the unadjusted odds ratios were made for all studies, as well as for sub-groups
      defined by an index of study quality, background prevalence of C trachomatis, and
      the contraceptive comparison being made. LOCATION: Studies in the analysis were
      mainly conducted in Europe and North America; the meta-analysis was done at the
      Harvard School of Public Health, Boston, MA, USA. RESULTS: The pooled estimated
      unadjusted odds ratio for 29 case-control studies examined was 1.93 (95% CI, 1.77
      2.11), indicating an almost twofold increased risk of chlamydial infection for
      oral contraceptive users. Neither study quality nor prevalence of C trachomatis
      modified this risk. When compared to the use of barrier contraceptives, however,
      the risk of infection for women using oral contraceptives increased to 2.91 (95%
      CI, 1.86-4.55). The pooled estimated protective effect of barrier methods in
      these studies was 0.34 (95% CI, 0.22-0.54). CONCLUSIONS: Cross-study comparisons
      of the relationship between oral contraceptive use and chlamydial infection are
      limited by the design and analysis of many component studies which did not
      control for confounding factors such as sexual behaviour and age. The almost
      twofold risk of increased chlamydial infection for oral contraceptive users,
      supported by the findings of two prospective studies, however, points to the
      importance of considering the risks and benefits of oral contraceptive use in
      women who are likely to be exposed to C trachomatis and other STDs. The
      protective effect of barrier methods emphasizes the continued need for promoting
      barrier methods of contraception.

PMID- 1398656
TI  - Seroepidemiological and socioeconomic studies of genital chlamydial infection in
      Ethiopian women.
AB  - OBJECTIVE: To measure the prevalence of chlamydial genital infection in Ethiopian
      women attending gynaecological, obstetric and family planning clinics; to
      identify the epidemiological, social and economic factors affecting the
      prevalence of infection in a country where routine laboratory culture and
      serological tests for chlamydial species are unavailable; to determine the risk
      factors for genital chlamydial infection in those with serological evidence of
      other sexually transmitted diseases. SUBJECTS: 1846 Ethiopian women, outpatient
      attenders at two teaching hospitals and a mother and child health centre in Addis
      Ababa, Ethiopia. SETTING: Gynaecological outpatient department, antenatal,
      postnatal and family planning clinics. METHODS: Sera were tested for type
      specific anti-chlamydial antibodies using purified chlamydial antigens (C.
      trachomatis A-C (CTA-C), C. trachomatis D-K (CTD-K), Lymphogranuloma venereum
      (LGV1-3), and C. pneumoniae (CPn)), in a micro-immunofluorescence test. The
      genital chlamydia seropositivity was analysed against patient's age, clinic
      attended, ethnic group, religion, origin of residence, age at first marriage and
      first coitus, income, number of sexual partners, duration of sexual activity,
      marital status/profession, obstetric and contraceptive history, and
      seropositivity for other sexually transmitted diseases. RESULTS: Overall exposure
      to chlamydia species was found in 84%, genital chlamydial infection in 62%, and
      titres suggestive of recent or present genital infection in 42% of those studied.
      Genital chlamydial infection was highest (64%) in family planning and lowest
      (54%) in antenatal clinic attenders. Exposure to genital chlamydia species was
      influenced by ethnic group and religion. Those married and sexually active under
      13 years of age had greater exposure (69%) to genital chlamydial infection than
      those first sexually active aged over 18 (46%). Prevalence of infection was
      highest in those with more than five sexual partners (78%) and in bargirls (84%).
      The lowest income groups had a higher prevalence (65%) of genital chlamydial
      infection than the wealthiest (48%). Multivariate analysis showed the most
      important factors to be age at first coitus, religion, prostitution and present
      age of the woman in that order. Risk for genital chlamydial infection was
      increased in those with seropositivity for syphilis, gonorrhoea, HSV-2 but not
      HBV infection. CONCLUSION/APPLICATION: Chlamydial genital infections are highly
      prevalent in both symptomatic and asymptomatic Ethiopian women. The high
      prevalence of infection reported reflects a complexity of socioeconomic factors:
      very early age at first marriage and first coitus, instability of first marriage,
      subsequent divorce and remarriage or drift into prostitution, all of which are
      influenced by ethnic group, religion and poverty--together with transmission from
      an infected group of prostitutes by promiscuous males to their wives, lack of
      diagnostic facilities and inadequate treatment of both symptomatic and
      asymptomatic men and women. The problem of chlamydial disease in Ethiopia needs
      to be addressed urgently in the context of control of STD.

PMID- 1398657
TI  - Incorporating patients' views in planning services for women with HIV infection.
AB  - OBJECTIVES: To determine the preferences of HIV seropositive women for out
      patient care facilities. DESIGN: Cross sectional survey. SETTING: An HIV out
      patient clinic, a genitourinary medicine (GUM) clinic and a self support group
      for HIV seropositive women. SUBJECTS: Fifty consecutive HIV seropositive women
      attending the out-patient clinic and 18 women attending the self support group.
      RESULTS: Eighty percent of the women were comfortable in the HIV clinic. The
      discomfort felt by the remainder related to time spent in the waiting room. All
      the women reported feeling comfortable in the GUM clinic. However, 46% indicated
      a preference for a clinic attended only by female patients and 34% stated that
      they preferred only female staff. At the time of the survey only 61% of women
      attending the self support group were attending an outpatient clinic. An HIV
      clinic with integrated family planning, gynaecology, social workers and a creche
      was a universal preference expressed by these women. They also indicated a
      preference for female doctors (83%). CONCLUSION: Women with HIV infection have
      clear views on the facilities which they would prefer to be available in regard
      to their out-patient care. In response to these wishes and particularly because
      of the high percentage of women not currently attending for outpatient care we
      have commenced a women only clinic.

PMID- 1398658
TI  - AIDS related primary intrathoracic lymphoma.

PMID- 1398659
TI  - Teenagers and the risks of sexually transmitted diseases: a need for the
      provision of balanced information.
AB  - OBJECTIVE: Evaluation of teenagers' knowledge and understanding about sexually
      transmitted disease, conception and contraception. DESIGN: A questionnaire study.
      SETTING: Schools SUBJECTS: 1025 teenagers aged 15/16 years (mean 16.00). MAIN
      OUTCOME MEASURES: Scores attained in response to questions about sexually
      transmitted disease related to the sources of information given as most helpful.
      RESULTS: Teenagers have an incorrect understanding of the risks of sexually
      transmitted diseases. CONCLUSIONS: Teenagers may substantially underestimate
      their personal risk of contracting sexually transmitted diseases following the
      promotion of information about HIV/AIDS. Apparently simple messages about HIV and
      AIDS given in mass media advertising programmes may have unwanted results and
      need to be balanced by appropriate professional interpretation to teenagers.

PMID- 1398662
TI  - Transmission of HIV-1 infection by oroanal intercourse.
AB  - We report the cases of two homosexual men, one of whom is believed to have been
      infected with HIV-1 during oroanal intercourse with the other, his only current
      sexual partner. Both patients had sero-conversion illnesses with similar symptoms
      and signs, and of similar duration. The practise of oroanal intercourse is known
      to be associated with the transmission of enteric infections and has been
      implicated in the epidemiology of Kaposi's sarcoma. These well-documented cases
      indicate that HIV-1 may also be transmitted by this route and supports a cautious
      approach to recommendations regarding "safer" sex.

PMID- 1398660
TI  - Sexual behaviour in Zulu men and women with genital ulcer disease.
AB  - OBJECTIVE--To investigate patterns of sexual behaviour in men and women with
      genital ulcer disease (GUD) and their relevance to HIV-1 transmission. METHODS--A
      sexual behaviour questionnaire was administered by the same interviewer to all
      participants who were also entered into a study of the microbial aetiology of
      GUD. SETTING--City Health Sexually Transmitted Diseases Clinic, King Edward VIII
      Hospital, Durban, South Africa. PARTICIPANTS--100 Zulu men and 100 Zulu women.
      RESULTS--36 (%) of men and 36 (%) of women had continued with sexual intercourse
      despite GUD. Patients with donovanosis and secondary syphilis were more likely
      than those with other causes of GUD to have intercourse despite ulcers. During
      swab collection bleeding was observed from ulcers in 59 women and 26 men.
      Prostitutes were not identified and were rarely named as source contacts. Men had
      more sexual partners (190) than women (122) during the previous three months.
      Condom use was minimal. Men who migrated between urban and rural areas appeared
      to have the most sexual partners. Urban women had more partners than women from
      rural areas. CONCLUSIONS--Men and women with GUD are practising riskful sexual
      behaviour and could benefit from behaviour modification programmes. In this
      community men who travel between urban and rural areas and who present late with
      GUD that bleeds easily are probably the most important high-frequency HIV
      transmitter core group. A significant potential risk of blood to blood contact
      during sexual intercourse exists in patients with GUD.

PMID- 1398663
TI  - Concurrent salmonellosis and histoplasmosis in AIDS: an unusual co-existence in
      Britain.
AB  - A patient is described with systemic salmonellosis which was unresponsive to
      therapy. Histoplasma capsulatum was isolated after death and we suggest that
      dysfunction of the reticuloendothelial system by H. capsulatum may have altered
      the prognosis.

PMID- 1398661
TI  - IgM rheumatoid factor removal and performance of the FTA-ABS (IgM) test in
      congenital syphilis.
AB  - OBJECTIVE: To determine the performance of the FTA-ABS (IgM) test in congenital
      syphilis after eliminating interference by IgM rheumatoid factor (RF) and
      preventing competitive inhibition by IgG. DESIGN: The FTA-ABS (IgM) test was
      carried out before and after RF removal (achieved by immunoprecipitation of the
      IgG) in infants with congenital syphilis and controls. SETTING: Newborns
      delivered in the Peninsula Maternal and Neonatal Services in Cape Town and
      infants presenting at Red Cross War Memorial Children's Hospital. SUBJECTS:
      Infants with congenital syphilis aged 0-4 months were divided into those with
      clinical signs at presentation and those who were asymptomatic at delivery. In
      addition, patients without congenital syphilis but with similar clinical signs at
      presentation were investigated as were control infants. OUTCOME MEASURE: The
      diagnosis of congenital syphilis was based on the criteria suggested by Kaufman
      et al (1977). RESULTS: Amongst symptomatic infants with congenital syphilis the
      FTA-ABS (IgM) test was positive in 34 (92%) of 37 cases prior to abolishing the
      RF effect and in 29 (78.4%) of 37 cases afterwards (p = 0.19). In 12 cases of
      congenital syphilis who were asymptomatic at birth, 10 had positive FTA-ABS (IgM)
      tests before RF removal and only three had positive tests afterwards (p = 0.006).
      False positive tests were not found amongst 15 symptomatic infants whose clinical
      features mimicked those of the infants with congenital syphilis. Among 51 healthy
      infants the test had a false-positive rate of 2% in newborns and 13% in older
      infants. The false positive reactions were eradicated by IgG precipitation.
      CONCLUSIONS: Following IgG and RF removal there was an improvement in the
      specificity of the FTA-ABS (IgM) test but this was at the expense of a loss of
      sensitivity, particularly in asymptomatic newborns. For newborns, if the FTA-ABS
      (IgM) test was positive, the patient was likely to require treatment for
      congenital syphilis, regardless of whether the result was due to the presence of
      RF or specific IgM.

PMID- 1398665
TI  - A serological test for granuloma inguinale.
AB  - OBJECTIVES: An indirect immunofluorescence technique applied to paraffin embedded
      tissue sections of lesions containing Donovan bodies was evaluated as a
      serological test for the diagnosis of granuloma inguinale. METHODS: Sera from
      patients with proven granuloma inguinale, other sexually acquired genital
      ulcerations and blood donors from areas where granuloma inguinale is rarely
      encountered as well as from disease-endemic regions were tested. Sera were tested
      either unabsorbed or following absorption with whole Klebsiella pneumoniae
      bacteria. RESULTS: Using unabsorbed sera at a dilution of 1:160 the test was
      found to have a sensitivity of 100%, specificity of 98%, positive predictive
      value (PPV) of 89% and negative predictive value (NPV) of 100%. There proved to
      be no advantage in preabsorbing sera with K. pneumoniae antigen. CONCLUSIONS: In
      the absence of culture methods for Calymmatobacterium granulomatis, an indirect
      immunofluorescence technique may prove valuable for the diagnosis of individual
      cases of granuloma inguinale and as an epidemiological tool in studies of the
      disease.

PMID- 1398664
TI  - Laboratory techniques in the diagnosis and assessment of hepatitis B virus
      infection.

PMID- 1398666
TI  - Multifocal bone tuberculosis in one AIDS patient.

PMID- 1398667
TI  - Terminology in cervical cytology/cervical histopathology.

PMID- 1398668
TI  - Treatment failure using double dose ciprofloxacin in a case of highly resistant
      gonorrhoea.

PMID- 1398669
TI  - HIV testing in genitourinary medicine--sustained increased demand in 1991.

PMID- 1398670
TI  - In search of an optimum method for the sterilization of a cryoprobe in a sexually
      transmissible diseases clinic.

PMID- 1398671
TI  - World-wide distribution of high level tetracycline-resistant Neisseria
      gonorrhoeae.

PMID- 1398672
TI  - Health in education for all: enabling school-age children and adults for healthy
      living.
AB  - The goals of Education for All and Health for All are inseparably linked. Both
      aim at equity and must be achieved concurrently. Good health is essential for
      effective learning, and education is a powerful means of enabling children and
      adults to attain and maintain health and wellbeing.

PMID- 1398673
TI  - School health education at the crossroads.
AB  - There are about one billion [corrected] young people of school age in the world
      today. Out of this number, hundreds of millions are actually attending school.
      They constitute the greatest single readily reachable population group providing
      the ideal opportunity for achieving a brighter health future.

PMID- 1398674
TI  - Life, health and the community. Making education truly comprehensive.

PMID- 1398675
TI  - Teacher support for comprehensive school health education.

PMID- 1398676
TI  - School health education in Scotland: the health promoting school encouraging
      parental involvement.

PMID- 1398677
TI  - Primary school health. Where are we and where are we going? Realities in the life
      of schoolchildren in the Third World.

PMID- 1398679
TI  - Implementing comprehensive school health education/promotion programmes.

PMID- 1398678
TI  - The role of the European Community in school health education.

PMID- 1398680
TI  - Comprehensive school health education: suggested guidelines for action.
AB  - This document is an outcome of the WHO/UNESCO/UNICEF Consultation on Strategies
      for Implementing Comprehensive School Health Education/Promotion Programmes held
      in WHO, Geneva from 25 to 29 November 1991. Twenty-five experts attended from the
      health education sectors of sixteen countries, as well as six NGOs together with
      the three cosponsors WHO, UNESCO and UNICEF plus UNFPA. The Consultation arrived
      at a consensus on a comprehensive approach to school health education and guiding
      principles for action.

PMID- 1398681
TI  - Selecting measures for human factors research.
AB  - Selecting measures is a necessary component of human factors research. Proper
      selection must take into account the representation problem (how is the
      assignment of numbers to objects or phenomena justified?) and the uniqueness
      problem (to what degree is this assignment unique?). Other key human factors
      measurement issues include subject representativeness, variable
      representativeness, and setting representativeness. It is difficult to create a
      single measure that captures essential characteristics of complex systems.
      Several examples illustrate how theory can guide measurement selection in such
      diverse human factors research as vigilance, turning off warning alarms,
      information requirements for military command centers, subjective workload, heart
      rate signal analysis, and heat stress in nuclear power plants.

PMID- 1398682
TI  - Establishment and characterization of monoclonal antibodies to carbohydrate
      antigens on peanut agglutinin receptor glycoprotein of gastric cancer KATO-III.
AB  - Eight mouse monoclonal antibodies, GOM-1, GOM-2, GOM-3, GOM-5, GOM-6, GOM-7, GOM
      8 and GOM-9 were established that recognized carbohydrate antigens on the human
      gastric cancer cell line KATO-III. Their binding specificities were studied by
      enzyme-linked immunosorbent assay, cellular enzyme-linked immunosorbent assay,
      flow cytometry analysis and thin layer chromatography immunostaining. All these
      monoclonal antibodies bound to peanut agglutinin receptor glycoproteins and
      neutral glycolipids extracted from KATO-III cells, but they could be divided into
      three groups, namely GOM-1, -3, -9 group, GOM-5 and GOM-2, -6, -7, -8 group. GOM
      3 specifically bound to the Le(a) structure, Gal beta 1-3 (Fuc alpha 1-4) GlcNAc
      beta 1-, and GOM-5 specifically bound to the Lec structure, Gal beta 1-3GlcNAc
      beta-. GOM-2 showed specific binding to KATO-III, but little or no binding to
      various other cell lines examined or to normal human leukocytic cells. It also
      did not bind to the synthetic glycoconjugates tested, carrying 10 different
      terminal sugar chains including T, Tn, Le(a), Lec and Le(x) structures. The
      binding specificity of GOM-2 was also different from those of the monoclonal
      antibodies anti-Le(x), anti-Leb and anti-Ley. These results suggest that GOM-2
      recognizes a new carbohydrate antigen on KATO-III cells that is distinct from
      Le(a), Leb, Lec, Le(x), Ley, T and Tn structures.

PMID- 1398683
TI  - Quadroma-secreted bi(interferon alpha 2--peroxidase) specific antibody suitable
      for one-step immunoassay.
AB  - A mouse hybridoma (quadroma) was prepared by fusing hybridomas producing
      monoclonal antibody of G1-isotype to human interferon-alpha 2 with hybridomas
      producing monoclonal antibody of G2a-isotype against horseradish peroxidase. The
      established quadroma line secreted immunoglobulins of both G1/G2a-isotypes which
      manifested parental and bispecific binding characteristics. Culture supernatant
      containing the bifunctional antibody cross-linking interferon and peroxidase was
      used for a one-step immunoassay. The developed sandwich ELISA was able to detect
      the human interferon-alpha 2 at a concentration of 10 units/ml (0, 1 ng/ml)
      within 2-3 hours.

PMID- 1398684
TI  - Human hybridoma generation by hypo-osmolar electrofusion: characterization of
      human monoclonal antibodies to Schistosoma mansoni parasite antigens.
AB  - Human monoclonal antibodies which bind Schistosoma mansoni worm and egg antigens
      were identified and characterized from hybridomas generated using the hypo
      osmolar electrofusion technique of somatic cell fusion. Splenocytes from S.
      mansoni infected individuals were mitogen-activated in vitro and subsequently
      fused by electrofusion. The greatest number of HAT resistant hybridomas per
      helical fusion chamber was obtained with unfrozen splenocytes cultured for 4-6
      days after introduction of mitogen. Hybridomas secreting IgG antibodies
      recognizing parasite antigens were identified by ELISA. Twenty-one cloned cell
      lines secreting IgG antibody were maintained for at least 6 months.
      Characterization of antigen reactivity by Western blot analysis of nien cloned
      cell lines revealed antibodies which bound stage specific parasitic antigens. The
      data show that the technique of hypo-osmolar electrofusion produces stable,
      antibody producing hybridomas. The human monoclonal antibodies screened represent
      candidate molecules useful in the investigations of the human pathogen S.
      mansoni.

PMID- 1398685
TI  - Preparation of monoclonal antibodies against acid alpha-D-glucosidase for study
      of Chinese glycogenosis type II patients.
AB  - Two monoclonal antibodies (Mabs), 8-23 and 4-6, against human acid alpha-D
      glucosidase were generated to analyse the intracellular alpha-D-glucosidase from
      seven Chinese Pompe's disease families with the following study design: [1]
      Purified alpha-D-glucosidase from normal human urine was used as antigen for
      immunization of mice. [2] The splenic cells of immunized mice were isolated and
      fused with myeloma cells NS-1 for generation of hybridomas and production of anti
      human alpha-D-glucosidase Mabs and detection of presence of the enzyme in skin
      fibroblasts obtained from the Pompe's disease families and normal controls. [3]
      Functional assay of acid alpha-D-glucosidase was done. Both generated Mabs were
      IgG1 with a kappa light chain. Mabs 8-23 and 4-6 can recognize 70 kd
      (kilodaltons) alpha-D-glucosidase evidenced by radioimmunoprecipitation (RIP).
      Our results showed that alpha-D-glucosidase did exist in the skin fibroblasts of
      all seven Pompe's disease patients by RIP and in the hepatic cells by
      immunohistological study. However, functional assay of alpha-D-glucosidase of the
      seven patients with Pompe's disease showed that the enzyme function of alpha-D
      glucosidase was defective. This finding is at variance with the results of other
      workers which indicated that the amount of mature enzyme was reduced or totally
      absent in most of the juvenile and adult Caucasian and South African patients.
      The discordance may imply that the cause of alpha-D-glucosidase deficiency in
      Chinese patients is quite different from that in Caucasian and South African
      patients. This needs further study to clarify.

PMID- 1398687
TI  - The development of new pacemaker electrodes.

PMID- 1398686
TI  - Quantification of glomerular epithelial cell adhesion by using anti-DNA
      antibodies in ELISA.
AB  - A sensitive and reproducible microassay is described for quantification of
      adhesion of cells to matrix-coated 96-wells plates under different experimental
      conditions. For this purpose glomerular visceral epithelial cells (GVEC) were
      used. Attached GVEC were fixed with methanol and incubated with a monoclonal anti
      DNA antibody. Following standard procedures, the amount of bound antibody was
      quantified by ELISA. A positive linear relationship in the range of 800-5000
      cells per well was found between OD values and cell numbers obtained by hand
      counting (r = 0.94, p less than 0.001). The assay is 10 to 100 times more
      sensitive than most other adhesion assays. The applicability of the ELISA assay
      was demonstrated by manipulation of the temperature during adhesion and by using
      different concentrations of the matrix-molecules fibronectin, EHS-laminin and
      collagen type I. The ELISA assay was found to be unaffected by non-specific
      interaction of anti-DNA antibodies with the matrix molecules used for coating.
      The assay was neither affected by potential release of DNA from the GVEC under
      these different experimental conditions. In conclusion, this cell adhesion
      microassay is simple, reliable, sensitive, and cost-effective, since it requires
      small amounts of GVEC and reagents.

PMID- 1398688
TI  - Angioplasty of total coronary occlusions using combination of intracoronary
      Probing Catheter and balloon on wire Probe.
AB  - We describe our experience with a technique for PTCA of total coronary occlusions
      using the ultra low profile balloon on wire Probe. An intracoronary Probing
      Catheter was used to facilitate crossing the stenosis with a guide wire. This was
      followed by exchanging the guide wire for the Probe into the obstruction for
      balloon dilatation. This technique was used in 22 consecutive patients undergoing
      PTCA for chronic total occlusion. The total obstruction could be crossed by guide
      wire (0.014 flex or 0.016 standard) passed through Probing Catheter in 19
      patients (86%). The obstruction could be successfully dilated by the Probe,
      delivered through the probing catheter, in 17 of these patients. Of the remaining
      2 patients, one could be dilated by sequential dilatation using over the wire low
      profile balloon system and the other one by dilatation with the Probe,
      respectively. The Probing Catheter technique offers a new method to apply balloon
      on wire technology to the dilatation of chronic total coronary occlusions with
      very promising results.

PMID- 1398689
TI  - Angioplasty of total coronary occlusions.

PMID- 1398690
TI  - Do hemodynamic indices correlate with maximum exercise capacity and oxygen
      consumption in chronic congestive heart failure?
AB  - The mechanism of exercise intolerance in chronic congestive heart failure remains
      unclear. We correlated resting haemodynamic variables with the peak exercise
      capacity and maximum oxygen consumption (VO2 max) in patients with congestive
      heart failure in 27 studies on treadmill exercise testing using the modified
      Bruce protocol. VO2 max was measured using breath by breath expiratory gas
      analysis. The patients were in severe congestive heart failure (NYHA class II and
      III, pulmonary artery wedge pressure 23 +/- 2 mmHg, cardiac index 2.4 +/- 0.21
      l/min/m2). VO2 max was 23 +/- 2 ml/kg/min. Fatigue was the commonest symptom
      limiting the exercise. None of the hemodynamic variables correlated well with VO2
      max. [right atrial pressure (r = 0.08), pulmonary artery pressure (r = 0.05),
      pulmonary artery wedge pressure (r = 0.08), aortic pressure (r = -0.3) & cardiac
      index (r = 0.29)]. Both uni- and multi-variate analysis failed to show any
      relation between VO2 max and resting hemodynamic variables. We conclude that
      unlike the acute heart failure syndromes, resting hemodynamic variables do not
      correlate with exercise capacity in patients with chronic congestive heart
      failure. The abnormal resting haemodynamics do not limit exercise in these
      patients. Peripheral mechanisms may thus be more important.

PMID- 1398691
TI  - Cross sectional echocardiographic left ventricular ejection fraction: method
      based variability.
AB  - Cross-sectional echocardiographic left ventricular ejection fraction (LVEF) by
      five different Methods (Teichholz, Area-length, single-plane Simpson, Bullet and
      Baran Formulae) was determined in 24 normal healthy volunteers (male-17, female
      7, age range 16-80 years, mean 37 +/- 13) to assess the method-dependent
      variability in left ventricular volumes and LVEF. Although the Teichholz and
      Bullet methods gave somewhat higher values, there was no significant difference
      between LVEF determined by any of the methods (F = 0.16, p greater than 0.50).
      There was an a symmetrical distribution of LVEF in this normal group with an
      absolute mean positive skewness of 6 per cent (range 4-7 percent, coefficient of
      skewness = +0.43 to +0.87). A cut-off normal lower limit of LVEF at 50 per cent
      encompassed 88-100 per cent (mean 93.3) of subject population depending upon the
      method used. Similarly there was no significant difference between left
      ventricular volumes obtained by various methods. Therefore all the above five
      methods for quantitation of left ventricular global function are equally useful
      in clinical studies in patients with normal left ventricular geometry and in
      absence of segmental asynergy.

PMID- 1398692
TI  - Assessment of left ventricular diastolic function in young diabetics--a two
      dimensional echo Doppler study.
AB  - Left ventricular diastolic function was assessed in 21 young diabetic subjects
      (less than 35 years) by Doppler transmitral flow velocity examination and
      compared with an equal number of matched controls. Diabetic subjects had higher
      heart rates (89 +/- 2 vs 79 +/- 4 beats/minute, p less than 0.015), peak late
      diastolic (A) velocity and a velocity time integral (56.6 +/- 13.4 vs 45.3 +/-
      11.4 cm/sec. p less than 0.005 and 7.3 +/- 5.2 vs 6.5 +/- 2.5 cm p less than 0.03
      respectively) and total transmitral flow velocity integral (25.8 +/- 5 vs 22 +/-
      3.2 cm, p less than 0.05). Peak E velocities, E velocity time integrals, E/A
      ratio, and peak filling rates were similar in two groups (p = not significant).
      These data suggests that young patients with diabetes mellitus have normal left
      ventricular diastolic function. The minor transmitral flow abnormalities are
      possibly due to autonomic dysfunction, e.g. increased sympathetic activity
      resulting in increased heart rate and cardiac output.

PMID- 1398693
TI  - Semi-quantitative planar scintigraphy using thallium 201 for detection and
      localization of coronary artery disease: correlation with coronary angiography.
AB  - Thallium 201 exercise redistribution planar myocardial perfusion scan using
      semiquantitative technique was performed in 80 symptomatic patients undergoing
      coronary angiography. Out of the 240 vessels studied by angiography, more than
      70% luminal narrowing was detected in 87 vessels, borderline stenosis was found
      in 49 arteries and the remaining 104 vessels were normal. Thallium scan correctly
      identified the significant stenosis in 76 vessels and the absence of stenosis in
      102 vessels. In addition, perfusion abnormality was found in relation with 21
      vessels of borderline stenosis. The sensitivity and specificity of Thallium scan
      were estimated as 92% and 95% for left anterior descending artery (LAD), 79% and
      98% for left circumflex artery (LCX), 88% and 100% for right coronary artery
      (RCA) and 87% and 98% for all coronary arteries combined together (ACA).

PMID- 1398694
TI  - A comparative evaluation of metoprolol and methyldopa in the management of
      pregnancy induced hypertension.
AB  - Thirty patients matched for age, parity, socioeconomic status and severity of
      pregnancy induced hypertension (PIH) were randomly allocated to treatment with
      metoprolol or methyldopa. The average fall in diastolic blood pressure was
      significant in the group treated with metoprolol as compared with the methyldopa
      group (p less than 0.01). There were 3 perinatal deaths in the methyldopa group
      and 1 in the metoprolol group; the mean birth weight of the babies was higher in
      cases treated with metoprolol. The results suggest metoprolol to be more
      efficacious with regard to control of hypertension and fetal outcome in cases of
      pregnancy induced hypertension.

PMID- 1398695
TI  - Congenital complete heart block in structurally normal heart--a study of 44
      cases.
AB  - Data of 44 patients with congenital complete heart block and structurally normal
      heart have been analysed. Thirty one patients were asymptomatic (group I) and 13
      patients had symptoms of low cerebral perfusion like syncope, near syncope or
      convulsions (group II). A ventricular rate on surface ECG was found to be
      significantly lower in the symptomatic group (56.7 +/- 13.2 beats per minute,
      bpm, in group I and 46.5 +/- 6.0 bpm in group II). Similarly wide QRS escape
      rhythm of greater than 0.10 seconds was more often seen in group II (2/13) as
      compared to group I (2/31) though the difference did not reach statistical
      significance. Presence of pauses of more than 3.0 seconds on ambulatory ECG
      monitoring were infrequent in both the groups (group I 1/7, group II 2/7),
      however more often seen in group II. Electrophysiological studies carried out in
      11 patients were not helpful in differentiating the two groups and all the
      patients including two with a wide QRS escape rhythm on surface ECG showed
      suprahisian level of block. The corrected junctional recovery time in two groups
      did not show any statistical difference. A persistently slow ventricular rate of
      less than 50 bpm during waking hours, wide QRS escape rhythm and pauses of
      greater than 3 seconds on ambulatory monitoring are suggestive of high risk to
      the patient and may justify implantation of permanent pacemaker even in
      asymptomatic patients.

PMID- 1398696
TI  - Low dose amiodarone in refractory tachyarrhythmias.
AB  - Fifty patients with drug resistant tachyarrhythmias were treated with amiodarone
      for 6-22 months; 16 for recurrent ventricular tachycardia (VT), 2 for VT followed
      by ventricular fibrillation (VF), 14 for complex ventricular ectopics, and 18 for
      supraventricular tachyarrhythmias (SVT). Amiodarone was administered in a dose
      much lower than that used in western trials. The actual incidence of successful
      amiodarone therapy was 81.2% at 22 months for patients with VT. Among the
      patients with SVT, 88.6% patients were successfully treated for 22 months (range
      3-22 months). Amiodarone toxicity appeared in 22 of 50 patients (44%) treated for
      more than 12 weeks. Withdrawal of therapy was required in 4 patients. Despite the
      lower dose, clinical efficacy and onset of action were comparable to the western
      experience.

PMID- 1398697
TI  - Carpentier's technique for repair of Ebstein's anomaly.

PMID- 1398698
TI  - Unusual response of pulmonary vasculature after Senning operation for complete
      transposition, intact ventricular septum and elevated pulmonary vascular
      resistance--a report of 2 cases.

PMID- 1398699
TI  - Salmonella myopericarditis presenting with acute pulmonary oedema.

PMID- 1398700
TI  - Chronic rheumatoid pericarditis.

PMID- 1398701
TI  - An analysis of initial results of percutaneous transluminal coronary angioplasty
      for totally occluded coronary arteries.
AB  - A retrospective analysis of 680 Percutaneous Transluminal Coronary Angioplasties
      (PTCA) performed from April 1986 to October 1990 revealed that 81 patients had
      PTCA performed on 86 totally occluded coronary arteries (1.06 lesions/patient).
      Four of the 86 were acute occlusions. Angiographic success in the group as a
      whole was achieved in 57 (66%). Multivariate analysis identified only the target
      vessel as a statistically significant factor predictive of angiographic success
      from among a host of clinical and angiographic morphologic variables. Left
      anterior descending artery lesions were identified with the highest success. In
      addition the duration of occlusion was significantly lower for the successfully
      versus the unsuccessfully dilated chronic occlusions.

PMID- 1398702
TI  - Membrane instability in respiring mitochondria: role of phosphate.
AB  - Metabolically-induced (spontaneous) high amplitude swelling of mitochondria has
      been shown to be due to a serial disruption of the mitochondrial membranes [D.
      Sambasivarao & V. Sitaramam (1985), Biochim Biophys Acta, 806, 195-209].
      Phosphate- and arsenate-induced swelling was investigated in mitochondria to
      evaluate the role of phosphate transport in the instability created in the
      mitochondrial membranes. Phosphate-induced swelling in respiring mitochondria was
      similar to spontaneous swelling. Both represent essentially colloidal swelling
      due to the variable porosity induced in the inner membrane to polyols by
      respiration. Swelling of non-respiring mitochondria at high ammonium phosphate
      concentrations was, on the other hand, primarily due to high permeability to
      phosphate. This membrane instability created by phosphate transport in the
      surrounding lipid involves neither the endogenous nor the exogenous Ca2+.

PMID- 1398703
TI  - Membrane skeletal protein structure and interactions in human erythrocytes after
      their treatment with diamide and calcium.
AB  - To analyse the role of native structures of membrane proteins in their structural
      modifications induced by the elevated intracellular free Ca2+ levels, we have
      studied the Ca(2+)-mediated effects on membrane skeletal proteins in human
      erythrocytes that were loaded with Ca2+ using the ionophore A23187 after their
      pretreatment with the sulphydryl oxidizing agent, diamide. The diamide treatment
      not only induced polymerization of the major membrane skeletal protein, spectrin,
      in the erythrocytes, but it also promoted intersubunit crosslinking within the
      tetramers and dimers of this protein. Loading of these diamide-treated cells with
      Ca2+ failed to induce significant structural modifications of spectrin as well as
      polypeptide 4.1, another major membrane skeletal protein, as compared to the
      erythrocytes that were loaded with Ca2+ without the diamide pretreatment. These
      results have been interpreted to suggest that the Ca(2+)-induced membrane
      skeletal protein changes in erythrocytes depend on both the shape and relative
      orientation of these proteins within the membrane skeleton.

PMID- 1398704
TI  - Molecular anatomy of the transcription complex of Escherichia coli during
      initiation.
AB  - Transcription is the foremost event in gene expression in which the enzyme RNA
      polymerase copies the genetic information from DNA to RNA. Much of our
      understanding of this process have come from studies carried out in Escherichia
      coli. A faithful and efficient transcription machinery of E. coli can be
      reconstituted in vitro with purified RNA polymerase and promoter-containing DNA.
      It is generally believed that in E. coli and most other organisms, the control of
      gene expression lies with the initiation of transcription. In this review, an
      attempt has been made to understand the mechanistic details of the initiation of
      transcription from the structural point of view of the promoter and the RNA
      polymerase. Allosteric nature of the enzyme has also been discussed at the end.

PMID- 1398705
TI  - Absolute reaction rate and kinetics of protein adsorption at solid-liquid
      interfaces.
AB  - Extents of adsorption of bovine serum albumin from aqueous solution to the
      surface of alumina, silica, carbon and chromium powder have been studied as
      function of time for various values of bulk protein concentration, pH, ionic
      strength and temperature. The rates of adsorption in all cases have been observed
      to fit in the first order rate equation with two different rate constants Ka1 and
      Ka2. Effects of addition of SDS, CTAB and neutral salts on values of Ka1 and Ka2
      have also been studied. Using Arrhenius equation the activation energy values Ea1
      and Ea2 have been evaluated from the values of Ka1 and Ka2 at three different
      temperatures, respectively. The corresponding values of enthalpy of activation
      (delta H*), entropy of activation (delta S*), and free energy of activation
      (delta G*) have been evaluated using Eyring's equation of absolute reaction rate.
      The mechanism of protein adsorption has been discussed in the light of basic
      principles of absolute reaction rate. It has been found that for Ka1 the delta
      H*1 greater than T delta S*1 and for Ka2 T delta S*2 greater than H*2, i.e. the
      anchorage and binding of protein to the surface are enthalpy controlled processes
      whereas the surface denaturation as well as rearrangement and folding is an
      entropy controlled process. The role of diffusion on rate of adsorption has also
      been discussed.

PMID- 1398706
TI  - Amphiphilic properties of polysaccharides: dextrin chains as example.
AB  - Polysaccharide chains are usually considered to be highly hydrophilic, since they
      contain no obvious apolar moieties. However, it is possible for even these chains
      to display hydrophobic character, arising out of stereochemical constraints in
      the chain. We had earlier shown that linear dextrin chains display amphiphilic
      properties, since all the hydroxyl groups are disposed on one side or face of the
      chain and the hydrogens disposed on the other. We provide further evidence here
      for this conclusion that dextrins are amphiphilic chains. In contrast, dextrans
      and cellulosic chains do not display amphiphilicity. Oligosaccharides that can
      adopt incipient helical structures might display amphiphilicity. This property
      might be relevant to intermolecular recognition on cell surfaces, lectin-sugar
      binding, antigen-antibody interactions and the like, and might be manifested more
      in a heteromolecular recognition process than as homomolecular self-aggregation.

PMID- 1398707
TI  - Mechanism of ribosomal subunit association: oligodeoxynucleotides as probes.
AB  - From the kethoxal treatment data [Herr, W.; Chapman, N.M.; Noller, H.F. (1979) J.
      Mol. Biol. 130, 433-439] some regions of ribosomal RNAs are thought to be
      responsible for the association of 30S and 50S ribosomes of E. coli to form 70S
      ribosomes. In order to test this possibility about a dozen oligodeoxynucleotides
      complementary to the suspected regions of rRNAs were synthesised. Their
      association with ribosomes and naked rRNAs was tested by the gel filtration
      technique. In order to check the effects on the ribosomal subunit association or
      rRNA association either intact 30S and 50S ribosomes or naked 16S and 23S rRNAs
      were preincubated with the individual oligodeoxynucleotide and its effect was
      checked by density gradient centrifugation followed by UV absorbance monitoring.
      Some oligodeoxynucleotides interfered with either subunit association or 16S RNA
      and 23S RNA association, some with both. These data clearly indicate that RNA-RNA
      interaction plays the major role in ribosomal subunit association.

PMID- 1398708
TI  - Effect of different proteolytic enzymes on the nature of subunit composition of
      arachins from groundnut (Arachis hypogaea L.).
AB  - Arachin, the major protein from groundnut, was isolated from three varieties of
      groundnut (Spanish Improved, TMV-2 and DH-3-30) using a modified procedure
      involving precipitation with 18% ammonium sulphate to obtain homogeneous protein.
      The homogeneity was judged by polyacrylamide gel electrophoresis, gel filtration
      and sedimentation velocity techniques as well as correlation with amino acid
      composition. Rates of hydrolysis of arachins by trypsin (pH 7.6) and alpha
      chymotrypsin (pH 7.8) were significantly different between the three varieties.
      Arachin from the Spanish Improved variety contained higher amounts of alanine and
      phenylalanine and lower amounts of carbohydrate and phosphorus as compared to TMV
      2 and DH-3-30. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis pattern
      of arachin from TMV-2 showed only seven bands of which the ones with low
      molecular weight were more intense than those of the other two varieties. The far
      ultraviolet circular dichroic spectra showed no significant differences among the
      three varieties in respect of alpha-helix content (5 +/- 2%), beta-structure (19
      +/- 2%) and the aperiodic structure. The observed differences in hydrolysis rates
      have been explained as due to the differences in the acidic and basic subunits of
      arachins.

PMID- 1398709
TI  - Heterogeneity in buffalo lutropin.
AB  - Lutropin (LH-1) from water buffaloes has been shown to exhibit microheterogeneity
      in the N-terminal amino-acid sequence of its alpha-subunit. The beta-subunit did
      not exhibit such microheterogeneity. Another protocol of purification yielded a
      preparation of buffalo LH (bu LH-2) different from the buffalo LH-1 in certain
      physico-chemical properties like ease of dissociation into subunits, sugar
      composition, isoelectric point, and elution profile on S-200. Data appear to
      indicate the presence of more than one form of buffalo lutropin.

PMID- 1398710
TI  - A stoichiometric analysis of bovine serum albumin-gossypol interactions: a
      fluorescence quenching study.
AB  - The interaction of gossypol with bovine serum albumin, human serum albumin and n
      bromosuccinimide-modified bovine serum albumin has been followed by fluorescence
      quenching measurements. The presence of a high affinity site (association
      constant K = 2.2 x 10(6) M-1) for gossypol on bovine serum albumin and human
      serum albumin is indicated. The stoichiometry of binding for the high affinity
      site was evaluated using Job's method of continuous variation, thereby suggesting
      the formation of 1:1 complex. Modification of the tryptophan residues on bovine
      serum albumin does not affect the binding of gossypol to either high or low
      affinity site of albumin.

PMID- 1398712
TI  - Involvement of active site in self-association of proteins: a case of alpha
      chymotrypsin.
AB  - The self-association of proteolytic enzymes can be looked upon as an interesting
      possibility of the manifestation of enzyme-substrate complex. Hence the
      involvement of active site in such processes is a centre of investigation for
      many years. In the case of alpha-chymotrypsin, considerable controversy exists
      with regard to the involvement of active site of the enzyme in its self
      association. A historical perspective of the problem and an overview of the
      available evidence, for and against, is presented and critically analysed.
      Despite contradicting observations, accumulated evidence indicates that His-57
      and Ser-195 at the active site are involved, at least partially, in the self
      association; a few other groups such as Tyr-146 and Met-192 are also involved in
      such processes.

PMID- 1398711
TI  - Partial amino acid sequence of sheep liver serine hydroxymethyltransferase and
      comparison of peptide maps of the enzyme from human, ox livers and Escherichia
      coli.
AB  - A comparison of the tryptic peptide maps of serine hydroxymethyltransferase from
      sheep, human, ox livers and Escherichia coli revealed that the mammalian enzymes
      were similar, while the bacterial enzyme exhibited differences in the primary
      structure. N-terminus of the reduced carboxymethylated sheep liver enzyme was
      acetylated. Serine hydroxymethyltransferase was hydrolyzed with trypsin and
      fragments of peptides were separated by high performance liquid chromatography
      using a combination of gel permeation, reverse phase and ion-pair chromatography.
      The peptides were sequenced manually using the 4-N,N'-dimethyl aminoazobenzene-4'
      isothiocyanate/phenyl isothiocyanate double coupling method. The tryptic peptides
      with 80% homology or above were aligned on the rabbit liver enzyme sequence.

PMID- 1398713
TI  - In vitro stimulation of microsomal diethyl nitrosamine deethylase activity by
      vitamin K3 (menadione).
AB  - Vitamin K3 (menadione) has been found to stimulate diethyl nitrosamine (DEN)
      deethylase activity in rat liver microsomes. The vitamin also takes care of the
      inhibitory effect of the anaerobic conditions as well as those of cytochrome
      poisons like sodium azide and sodium cyanide, possibly through production of
      active oxygen species. The enzyme was also stimulated by H2O2 and SOD and
      inhibited by catalase, thereby suggesting that H2O2 or some derivatives of it may
      be the active oxygen species involved in the reaction.

PMID- 1398714
TI  - Isolation and characterization of 5'-nucleotidase inhibitor from rat liver.
AB  - 5'-Nucleotidase (EC 3.1.3.5) is widely distributed in nature. However, it could
      not be detected in rat liver, because of the presence of specific inhibitors.
      Such inhibitors were also found in other tissues of rat, but at lower
      concentrations than that in the liver. The inhibitor activity was enriched in the
      membrane fraction and was also present in the cytosol fraction. It was sensitive
      to treatment with 6M urea and trypsin, while heating in a boiling water bath for
      10 min or dialysis reduced the activity only slightly. Gel filtration or Sephadex
      G-50 yielded two types of inhibitors. Inhibitor I inhibited brain 5'-nucleotidase
      while inhibitor II inhibited both the brain and liver enzymes. Inhibitor II on
      further purification on CM Sephadex C-25 yielded five fractions with inhibitor
      activity of which inhibitor IIC was electrophoretically homogeneous. It had a
      molecular weight of 8500 by SDS gel electrophoresis, was rich in basic amino
      acids and had a high proportion of beta structure. Interaction of the inhibitor
      with 5'-nucleotidase brought about modifications in the secondary structure of
      the inhibitor as seen from the circular dichroism spectrum.

PMID- 1398715
TI  - Microenvironment at the substrate binding subsite of the active site of
      UDPglucose 4-epimerase from Kluyveromyces fragilis using a fluorescent analog of
      UMP.
AB  - A chromophorics and fluorescent analog of uridine 5'-monophosphate (UMP), a known
      competitive inhibitor of UDPglucose 4-epimerase was synthesised. This analog,
      namely 2',3'-O-(2,4,6-trinitrocyclohexadienylidene) uridine 5'-monophosphate, was
      found to be a powerful reversible inhibitor of UDPglucose 4-epimerase indicating
      its interaction with the substrate binding site of the enzyme. The extreme
      sensitivity of the fluorescence emission spectrum of this analog to solvent
      polarity makes it an excellent probe for the study of the environment at the
      active site of the enzyme. We report here the effective use of this UMP analog to
      demonstrate that the hydroxyl groups of the ribose moiety of UMP and presumably
      the substrates (UDPgalactose and UDPglucose) do not reside in a hydrophobic
      milieu.

PMID- 1398716
TI  - Studies on the role of iron binding ligands and the intestinal brush border
      receptors in iron absorption.
AB  - With a view to identifying ligands that could be used as promoters of iron
      absorption, the affinity of a number of iron chelating agents and the efficiency
      with which they can donate iron to the brush border receptors has been studied. A
      number of organic and inorganic compounds were found to chelate iron and keep it
      soluble at pH 7.5 of the intestinal lumen. This ligand-bound iron was taken up by
      the intestinal brush border receptors with varying degree of efficiency; ascorbic
      acid being the most effective and EDTA and citrate the least effective in
      donating the chelated iron to the receptors. Several polyphosphate compounds,
      used as food additives, chelated iron and kept it in solution but showed moderate
      potency for donating iron to the receptors.

PMID- 1398717
TI  - Mechanism of lectin-cell interactions: thermodynamic and kinetic analysis of the
      binding of winged bean acidic lectin (WBA II) to human erythrocytes.
AB  - In order to identify the forces involved in the binding and to understand the
      mechanism involved, equilibrium and kinetic studies were performed on the binding
      of the winged bean acidic lectin to human erythrocytes. The magnitudes of delta S
      and delta H were positive and negative respectively, an observation differing
      markedly from the lectin-simple sugar interactions where delta S and delta H are
      generally negative. Analysis of the sign and magnitudes of these values indicate
      that ionic and hydrogen bonded interactions prevail over hydrophobic interactions
      resulting in net -ve delta H (-37.12 kJ.mol-1) and +ve delta S (14.4 J.mole-1 K-1
      at 20 degrees C), thereby suggesting that this entropy driven reaction also
      reflects conformational changes in the lectin and/or the receptor. Presence of
      two kinds of receptors for WBA II on erythrocytes, as observed by equilibrium
      studies, is consistent with the biexponential dissociation rate constants (at 20
      degrees C K1 = 1.67 x 10(-3) M-1 sec-1 and K2 = 11.1 x 10(-3) M-1 sec-1). These
      two rate constants differed by an order of magnitude accounting for the
      difference in the association constants of the two receptors of WBA II. However,
      the association process remains monoexponential suggesting no observable
      difference in the association rates of the lectin molecule with both the
      receptors, under the experimental conditions studied. The thermodynamic
      parameters calculated from kinetic data correlate well with those observed by
      equilibrium. A two-step binding mechanism is proposed based on the kinetic
      parameters for WBA II-receptor interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398718
TI  - The critical micelle condition revisited.
AB  - Several simple alternatives have been examined as a possible basis for micellar
      size distributions which are internally consistent with the experimentally
      required concept of a threshold concentration, the critical micelle condition.
      Among these are the two-state system, monomer in equilibrium with a single high
      polymer, indefinite self-association, and continuous self-association with an
      arbitrary upper limit beyond which all further association is absolutely
      prohibited. Of these, only the last is a possible choice, although lacking
      experimental support. This report considers in deeper detail a thermodynamic
      model for micelle distributions, the so-called shell model of the present author,
      which is in basic agreement with an earlier statistic-mechanical study [Hoeve CA
      & Benson GC (1957), Colloid Polym Sci, 252, 56] in predicting the possibility of
      broad distributions of micellar species. A self-consistent distribution model
      which predicts a critical micelle condition must also predict a location with
      respect to degree of polymerization having a minimum concentration. Thus, the
      molar distribution function for the shell model satisfies this requirement,
      whereas the equivalent concentration distribution function fails to do so, as
      would the statistical models for multiple ligand binding. Moreover, the position
      of this minimum is predicted to change with concentration.

PMID- 1398719
TI  - Structure-function relationships in proteins and peptides--a symposium in print.
      In honour of late Dr. M.S. Narasinga Rao and late Professor L.K. Ramachandran.

PMID- 1398720
TI  - Germ-cell tumours of the ovary--treatment and results at Cancer Institute,
      Madras.

PMID- 1398721
TI  - Congenital granular-cell myoblastoma.
AB  - Congenital granular-cell myoblastoma is a rare jaw tumor presenting in the
      neonatal period. The differentiation between congenital epulis and granular cell
      myoblastoma is a controversial issue amongst pathologists. It is a benign
      swelling in which simple excision is the treatment of choice. Here we report two
      cases with a brief review of literature.

PMID- 1398722
TI  - Malignant rhabdoid tumour of kidney. A case report.
AB  - A case of malignant rhabdoid tumour of kidney is reported. Interesting features
      are bony metastasis at presentation and FNAB diagnosis of metastasis.

PMID- 1398723
TI  - Malignant granular cell tumour. A case report and review of literature.
AB  - A rare case of malignant granular cell tumour of the anterior abdominal wall in a
      woman of 30 years is reported and and the relevent literature is briefly
      reviewed.

PMID- 1398724
TI  - Heterotopic bone formation in renal cell carcinoma (a case report).
AB  - A case of renal cell carcinoma with heterotopic bone formation occurring in a
      female aged 55 years has been reported. There was no haematuria and the
      morphological picture showed only ossified stroma and no sarcomatoid appearance.

PMID- 1398725
TI  - Mesenchymal chondrosarcoma of the paraspinal region: a case report.
AB  - Mesenchymal chondrosarcoma is a very uncommon tumor. An extremely rare
      presentation of the tumor i.e. arising from the paraspinal region is being
      presented.

PMID- 1398726
TI  - Colonic lipoma, masquerading as malignant tumour.
AB  - A case of symptomatic colonic lipoma, mimicking malignant tumour on colonoscopy,
      barium contrast studies and at laparotomy, is reported. The diagnosis was
      established on histopathology after left hemicolectomy.

PMID- 1398728
TI  - Aspergillosis of the paranasal air sinuses (case reports and review of
      literature).
AB  - Aspergillosis of the paranasal air sinuses is a rare entity. It is endemic in
      Sudan and a few states in South America. It affects healthy and immunocompromised
      individuals alike. It presents in two forms--the invasive and non-invasive
      Aspergillosis. The former is difficult to distinguish from carcinoma on clinical
      examination. Conventional radiographs of the sinus, a CT scan evaluation and a
      selective culture of the sinus fluid for fungus aid in achieving a positive
      diagnosis. The treatment of invasive Aspergillosis is always surgical--some form
      of antrostomy to facilitate sinus drainage or sinus excision supplemented with
      topical and/or systemic anti-fungal chemotherapy. The authors report two cases of
      Invasive Aspergillosis, clinically type 'benign' and 'malignant' of the paranasal
      air sinuses, affecting non-immunocompromised individuals. In both the cases,
      complete surgical excision was achieved.

PMID- 1398727
TI  - Synchronous bilateral parotid metastases from renal cell carcinoma. A case
      report.
AB  - An unusual case of bilateral synchronous parotid metastases from renal cell
      carcinoma presenting seven years after nephrectomy is reported. The patient
      underwent bilateral superficial parotidectomy and is alive free of disease three
      and half years after the metastatectomy.

PMID- 1398729
TI  - [Systematic lupus erythematosus and pregnancy].
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that affects
      primarily women of childbearing age. 20-30 years ago it was common belief that
      SLE is exacerbated during pregnancy. Recent studies, however, could not support
      this notion. The likelihood of an increase in clinical activity of SLE is similar
      during pregnancy and in nonpregnant patients. It correlates directly with the
      activity of disease at the time of conception. The pregnancy outcome in patients
      with SLE has improved considerably in recent years. The frequency of fetal loss,
      however, still remains higher in SLE patients than in healthy women. In most of
      the cases fetal loss is due to habitual abortions, intrauterine death and
      premature labors. The main reasons are anti-phospholipid antibodies and the
      activity of SLE at the onset of pregnancy, respectively during the pregnancy. For
      monitoring disease activity and especially for distinguishing between the
      development of eclampsia and exacerbation of SLE, periodic determinations of
      complement proteins CH50, C3, C4 and C3d are helpful. A prophylactic therapy e.g.
      with prednisone in pregnant SLE patients is not justified. However, when SLE is
      exacerbating immunosuppressive therapy with prednisone and, if needed in
      combination with azathioprine, should be administered. In cases with high
      antiphospholipid antibody titers and prior fetal loss a treatment with low-dose
      acetylsalicylic acid can be considered.

PMID- 1398730
TI  - [Neonatal lupus erythematosus as an example of passively acquired autoimmunity].
AB  - Neonatal lupus erythematosus is a typical example of passively acquired
      autoimmune disease. Congenital heart block is the main complication caused by
      transplacentally transferred maternal IgG antibodies directed against SS-A- or SS
      B-antigen. While the transient lupus dermatitis occurs post partum and is often
      triggered by UV-light exposition, the irreversible cardial damage takes place
      between the 18. and 24, week of pregnancy. During this period 52-kD-SS-A- and 48
      kD-SS-B-antigen are expressed in the fetal cardial tissue. The autoimmune
      reaction leads to an irreversible fibrotic destruction of the atrioventricular
      node. The resulting AV block and an antibody-induced perimyocarditis support the
      development of fetal bradyarrhythmia and hydrops. The very early diagnosis of a
      fetal heart block in bradycardiac fetus by echocardiography is essential for a
      consecutive therapy with steroids. By a reduction of the maternal antibodies an
      improvement of cardial symptoms in the fetus may be achieved in cases with fetal
      hydrops. Pregnant women at high risk with known connective tissue disease,
      previous children with congenital heart block, high titers of SS-A-/SS-B
      antibodies and immunogenetic predisposition (HLA-DR3) have to be monitored
      intensively because of the possibility of a prophylaxis with dexamethasone and,
      in some selected cases, plasmapheresis.

PMID- 1398731
TI  - [Antiphospholipid syndrome].
AB  - Antibodies against phospholipids in serum, lupus anticoagulant and
      anticardiolipin antibodies, are strongly associated with venous and arterial
      thrombosis. A syndrome characterized by these symptoms and the autoantibodies,
      the antiphospholipid syndrome, is found mostly in patients with systemic lupus
      erythematosus or related autoimmune disease, but is also found primary without a
      systemic disease.

PMID- 1398732
TI  - [Thirty years of cellular immunity].
AB  - Mackaness' original article about cellular resistance to infection, published in
      1962, is recalled. These experiments laid the foundation of the analysis of
      immune mechanisms against infection with facultatively intracellular
      microorganisms. Based on a simple murine model with Listeria monocytogenes, an
      array of data was compiled during three decades, clarifying the mechanism of
      inborn resistance and acquired immunity to this type of parasites. The idea of
      various immune cell populations cooperating via cytokines was developed and
      experimentally proven. Different forms of immunodeficiencies were conceived in
      the same model, and therapeutic approaches were evaluated. Thus, thirty years
      after the first publication, Mackaness' concept of cell-mediated immunity to
      infection is solidly based on experimental data, and is an integral part of our
      understanding of the mammal immune system.

PMID- 1398733
TI  - [The role of interleukin 1 in infection and sepsis].
AB  - Interleukin(IL-)-1 is the prototype of a proinflammatory cytokine, produced in
      response to infection and other forms of trauma. At low concentrations IL-1
      brings about increases in a number of defense mechanisms, particularly
      immunologic and inflammatory responses. However, over- or continued production of
      IL-1, as seen for example during septic infection, significantly contributes to
      pathological reactions such as hemodynamic shock. Thus, it is not surprising that
      IL-1 activities are tightly regulated, most notably at the levels of
      transcription and secretion. Additional regulation is provided by the action of a
      protein, that blocks the binding of IL-1 to its receptors. This protein, termed
      IL-1-receptor antagonist (IL-1ra) has been cloned recently, and may provide the
      possibility of specific therapeutic measures.

PMID- 1398735
TI  - [Ambulant atypical pneumonia: clinical diagnosis and therapy].
AB  - Atypical pneumonias are caused by mycoplasma, chlamydia and legionella species.
      From a clinical point of view the disease is comparable to influenza-like
      infections. Macrolide antibiotics covered the species which are most important.
      Especially new macrolides displayed better pharmacokinetic properties, allowing
      dose reduction and reduced frequency of intake. For legionella infections also
      therapy with modern quinolones is possible.

PMID- 1398734
TI  - [In vitro proliferation of human bone marrow cells--inhibition by components of
      Candida albicans].
AB  - Candida albicans (CA) components influence the proliferation of human bone marrow
      cells in vitro (colony-forming assay). Number of colonies per 10(5) bone marrow
      cells after cultivation with rHuGM-CSF (maximal plateau colony formation): 46.2
      +/- 9.1 (n = 6); after cultivation with rHuGM-CSF in combination with CA
      proteins: 0.05 mg protein/ml: 33.4 +/- 4.6 (n = 3); 0.10 mg protein/ml: 20.8 +/-
      3.6 (n = 3).

PMID- 1398736
TI  - Entamoeba histolytica extract and interferon-gamma activation of macrophage
      mediated amoebicidal function.
AB  - The effect of recombinant murine interferon-gamma (IFN-gamma) and E. histolytica
      extract (E.h.E.) on macrophage (M phi) activation for amoebicidal activity was
      examined. Peritoneal macrophages were harvested from C57BL/6 and A/J mice and
      preincubated with IFN-gamma and/or E.h.E. It was found that amoebicidal activity
      could be induced in both C57BL/6 and A/J-derived macrophages by pretreatment with
      IFN-gamma and E.h.E. Pretreatment of the M phi with E. histolytica extract or IFN
      gamma alone did not result in the activation of significant cytotoxic activity
      against E. histolytica trophozoites. In the presence of IFN-gamma, E.h.E. had a
      dose-dependent effect on the activation of M phi amoebicidal function.

PMID- 1398737
TI  - Modulation of type II collagen-induced arthritis in DBA/1 mice by intravenous
      application of a peptide from the C1q-A chain.
AB  - In this report we are able to show that intravenous (i.v.) application (day 0) of
      a nonapeptide (residues 26-34) from the human C1q A-chain (designated peptide A
      C1q) prior to intradermal (i.d.) administration of chicken type II collagen (CII)
      in arthritis-susceptible DBA/1 mice (H2q), leads to abrogation of
      polymorphonuclear neutrophil (PMN) invasion into the joints. This nonapeptide
      exhibits epitope characteristics and high homology to residues 137-147 of CB11 (a
      cyanogen bromide fragment of chicken CII, known to contain both arthritis
      inducing and suppressing determinants). Arthritis index was lowest in animals
      pretreated i.v. with CII (as internal control), though animals pretreated i.v.
      with peptide K (residues 137-147 with an additional glycine residue from CB11) or
      peptide A-C1q exhibited comparative arthritic indices. Only in the arthritis
      positive control group (day 0: PBS i.v.) did i.d. application of CII lead to
      invasion of PMN into the synovial layer and the joint space. Analysis of antibody
      (Ab) responses at day 48 after i.v. immunization (day 0) and CII challenge (day
      7) revealed IgE-Abs to native CII and also to native C1q. IgG titers to CII were
      highest in animals pretreated with peptide A-C1q. Abs from this group, exhibiting
      activity to peptide A-C1q (immunizing antigen), were of mainly IgG1 and IgG3
      isotypes. Evaluation of the immune response following i.v. application of peptide
      A-C1q or CII, prior to i.d. CII administration, in DBA/1 mice, revealed IgM
      responses to peptide A-C1q and peptide K, but not to CII. Intravenous application
      of peptide A-C1q led to generation of IgG3-Abs reacting only with peptide A-C1q
      and peptide K, but not with native CII. Additionally, i.v. application of peptide
      A-C1q elicited IgG responses to a pentapeptide, resembling amino acid residues 26
      30 (K-G-E-Q-G) of the C1q A-chain. This five residue antigenic determinant is
      present in peptide K, in chicken and human CII as well as in human C1q. No
      specific IgE response to any of the antigens tested could be detected. Since a
      peptide from the C1q A-chain is both capable of eliciting immune responses and
      modulating CII-induced arthritis in mice, we postulate that the collagen-like
      complement component C1q is involved in the development of CII-induced
      inflammatory arthritic lesions, and may represent, in vivo, the early antigen
      responsible for inducing anticollagen antibodies prior to CII in hyaline
      cartilage becoming available as antigen.

PMID- 1398738
TI  - Liposome mediated affection of monocytes.
AB  - Dichloromethylene diphosphonate (Cl2MDP) enclosed in liposomes, when injected
      intravenously, selectively eliminates all phagocytizing macrophages that are in
      direct contact with the blood circulation of the spleen and the liver. We
      examined whether Cl2MDP containing liposomes affect, in addition, rat monocytes
      and bone marrow macrophage precursors (BMMP's). In addition to
      Phosphatidylcholine-Cholesterol liposomes (PC liposomes), we also used
      mannosylated PC liposomes (PCMAN liposomes), which are reported to bind more
      efficiently to macrophages. Monocytes appeared to be affected 24 h after
      injections of 2 ml of Cl2MDP containing PC as well as PCMAN liposomes. In
      addition, almost no macrophages could be detected in one week cultures of blood
      leukocytes isolated from these animals; cultures from control animals contained
      +/- 50% macrophages. Bone marrow macrophage precursors did not appear to be
      affected.

PMID- 1398739
TI  - In vivo presentation of Mls-1 antigen by T and B lymphocytes.
AB  - Previous studies of minor lymphocyte stimulatory (Mls) presenting lymphoid cells
      had shown that B cells rather than T cells present stimulatory Mls-1 antigen in
      vitro whereas B as well as T cells present Mls-1 antigen in vivo. Deletion of Mls
      1 reactive T cells in the thymus of newborn mice is induced by T cells rather
      than by B cells. Applying a recently developed method for measuring the Mls-1
      response in Mls-1- mice we assessed the Mls-1 stimulatory activity of T and B
      cells quantitatively. B cells are significantly more effective than T cells in
      this process. Both Mls-1+ T and B cells are also capable of inducing Mls-1 anergy
      in Mls-1- mice. Remarkably few lymphoid cells from Mls-1+ animals are needed for
      this effect: a few thousand B cells or 10(4) to 10(5) T cells per mouse induce
      substantial Mls-1 anergy in Mls-1- mice. These low cellular requirements for Mls
      1 anergy production correspond well to the low T cell requirements described for
      the induction of Mls-1 tolerance in newborn mice. However, the high efficacy of B
      cells in inducing peripheral Mls-1 anergy contrasts with their failure to induce
      neonatal tolerance in newborn animals. We attribute this discrepancy to the
      previous notion that stimulatory Mls-1 antigen is not delivered to the thymus and
      that B cells and T cells present qualitatively different Mls-1 related signals to
      Mls-1 reactive T cells.

PMID- 1398740
TI  - Analysis of CD16+dim and CD16+bright lymphocytes--comparison of peripheral and
      clonal non-MHC-restricted T cells and NK cells.
AB  - The Fc gamma RIII receptor (CD16) has been described on natural killer cells and
      a small subset of T lymphocytes. CD16+bright lymphocytes represent the typical
      population of peripheral blood CD3- NK cells. In these studies in addition to
      CD16+bright NK cells Fc gamma RIII expressing cytotoxic T lymphocytes in
      peripheral blood from one healthy individual are characterized as CD16+dim non
      MHC-restricted CTLs either expressing the alpha/beta (80%) or the gamma/delta T
      cell receptor (20%). Both CD16+ subsets are clearly distinct in their functional
      capacity performing NK and ADCC activity. Freshly isolated CD16+dim T cells exert
      higher ADCC, CD16+bright NK cells higher NK activity. They are also
      differentially activated by interleukin-2 since CD16+bright NK cells reveal a
      bright expression of the p75 IL-2 receptor beta-chain in contrast to the very low
      p75 expression on CD16+dim T cells. This activation leads to a gradual increase
      of ADCC by NK cells. Finally the CD16 expression pattern with low and bright
      intensity represents a stable phenotype expressed by clones generated from these
      different subpopulations. On a clonal level CD16+dim non-MHC-restricted T cells
      can be distinguished from CD16+bright NK cells by their lower capacity in NK
      killing, but they are equally potent in ADCC. Finally these CD3+CD16+dim clones
      provide the basis for studies of Fc gamma RIII and TcR interaction.

PMID- 1398741
TI  - Human C5a anaphylatoxin: gene cloning and expression in Escherichia coli.
AB  - A gene coding for the human anaphylatoxin C5a was cloned and expressed in
      Escherichia coli. A combination of reverse transcription of mRNA of the U937 cell
      line with subsequent preparative polymerase chain reaction was employed to obtain
      the gene. The sequence was cloned into the plasmid vector pKK 233-2 behind an ATG
      initiation codon under the control of a trc promotor. After purification by ion
      exchange chromatography and reversed phase FPLC a mixture of predominantly non
      glycosylated recombinant human C5a with a beta-mercaptoethanol adduct at cysteine
      27 and the N-methionyl derivative was obtained which was homogeneous on silver
      stained gels, immunoreactive with C5a-specific monoclonal antibodies and
      functionally active in releasing myeloperoxidase from human granulocytes and ATP
      from guinea pig platelets. The final yield was about 0.4-0.8 mg purified
      recombinant C5a per liter bacterial culture.

PMID- 1398742
TI  - Resistance of different tumor cells to lysis by lymphokine activated killer cells
      can be mediated by distinct mechanisms.
AB  - Lymphokine activated killer (LAK) cells have been shown to exert a potent
      cytotoxic effect on many histologically different tumors and virally infected
      targets. Most normal cells but very few tumors have proven resistant to LAK
      lysis. The availability of two LAK resistant tumors, P815r, a murine mastocytoma,
      and SNUC-1, a human colon carcinoma, allowed us to study the phenomenon of LAK
      lysis. We examined the role of surface molecules on targets, which mediate
      binding to LAK cells, by cold target competition experiments and lectin dependent
      cellular cytotoxicity assays. The results showed that in the murine system, P815r
      cells do not compete for lysis of the LAK sensitive target B16 whereas other LAK
      sensitive murine targets compete. Alternatively, in the human system, SNUC-1
      cells compete for lysis of the LAK sensitive target SNUC-4 as do other LAK
      sensitive human tumor cells. Furthermore, inducing binding of target and effector
      cells with lectin reverted the resistance of P815r but not SNUC-1 targets to
      lysis by LAK cells. These results imply that distinct stages of the lytic pathway
      might be involved in the resistance of different tumors to killing by LAK cells.
      The murine cell line is resistant to lysis because it cannot bind LAK cells. The
      human target, which does bind LAK, was insensitive to the effects of tumor
      necrosis factor alpha (TNF-alpha), a lymphokine released by LAK effectors and
      possibly involved in their lysis. Resistance to TNF-alpha was not mediated by the
      presence of endogenous short-lived proteins in the SNUC-1 targets. The
      elucidation of mechanisms of resistance may provide a tool to improve current
      protocols of adoptive immunotherapy as well as insights as to how tumor cells are
      or are not killed by LAK effectors.

PMID- 1398743
TI  - Measurement of lymphocyte proliferation: critical analysis of radioactive and
      photometric methods.
AB  - Different methods of lymphocyte proliferation are compared to identify a non
      radioactive alternative to 3H-thymidine-test. The enzymatic assays evaluating the
      turnover of mitochondrial dehydrogenases (MTT-test) and lysosomal hexosaminidase
      (NAG-test) proved not sensitive enough to substitute for 3H-thymidine
      incorporation. The incorporation of the nucleotide analog 5-bromodeoxyuridine
      (BrdU) can be exploited using an ELISA-system (enzyme linked immunosorbent assay)
      employing a monoclonal anti-BrdU antibody to measure cell proliferation. An
      optimized test protocol of the BrdU-ELISA which fulfills the requirements for a
      sensitive and practicable non-radioactive alternative to 3H-thymidine-test is
      presented.

PMID- 1398744
TI  - Functional properties of heterogeneous human asialo-C4 and its isotypes C4A and
      C4B.
AB  - The fourth component of human complement (C4) is encoded at two separate but
      closely linked loci within the MHC on the short arm of chromosome 6. Thus, there
      are two types of C4 protein in most individual and pooled normal human sera
      (NHS): C4A and C4B. Incubation of individual sera, pooled NHS, or purified
      heterogeneous C4 (C4A/C4B) with bacterial sialidase at 37 degrees C increased C
      mediated hemolysis of antibody-sensitized sheep erythrocytes 1.54- to 1.93-fold.
      Comparative studies of Tmax of human C2, using asialo-C4 or buffer-treated C4 on
      EAC1gp and extrapolation to time 0 indicated a z value 4-fold higher with asialo
      C4. This indicated that more hemolytically active C42 complexes are available
      with sialidase-treated C4 compared to untreated C4. There was no appreciable
      difference in the % 125I-C4 bound to EAC1gp (sialidase- or buffer-treated). Sera
      from two different blood donors with C4A3 phenotype (C4BQ0), two different donors
      with C4B1 phenotype (C4AQ0), and serum from an individual heterozygous deficient
      at both C4A3 and C4B1 regions (A3, AQ0; B1, BQ0) were investigated. The C4
      allotypes, purified from these sera, were treated with sialidase; the C4A3 was
      enhanced in hemolytic assays by sialidase-treatment (1.52- to 2.3-fold), whereas
      the C4B1 allotype was not enhanced. Fluorometric determinations revealed that
      approximately the same percentage of sialic acid was released from sialidase
      treated C4A3 and C4B1. Therefore, the increase in hemolytic titer observed after
      treatment of NHS or purified heterogeneous C4 with sialidase is a property of
      C4A3 but not a property of C4B1.

PMID- 1398745
TI  - Relative expression of surface IgM, IgD and the Ig-associating alpha(mb-1) and
      beta(B-29) polypeptide chains.
AB  - Membrane immunoglobulins are associated with a transmembrane disulphide-linked
      heterodimer composed of an alpha-chain (mb-1) and a beta-chain (B-29). The
      relative surface expression of all of the polypeptide chains comprising the Ig
      alpha beta complex has been investigated using surface labelling coprecipitation
      analysis and two-colour flow cytometric analysis. The main conclusions are that
      mb-1 and B-29 are B-cell surface markers on immature and mature B cells, and that
      all components of the surface Ig-alpha beta complex are expressed in
      stoichiometrically equivalent amounts. Thus the complex was quantitatively
      precipitated from digitonin lysates of 125I-surface-labelled cells with anti-B
      29, anti-mb-1 or anti-Ig. Secondly, by two-colour FACS analysis there was a
      proportionality between the relative amounts of cell surface mb-1 or B-29 and
      surface IgM or IgD, but not other B-cell markers (class II, B220, FcR gamma, FcR
      epsilon). Finally there was an insignificant number of B cells expressing
      membrane Ig without alpha- and beta-chains, and vice versa. Thus there appears to
      be a closely controlled relative synthesis and surface expression of all
      components of the B-cell receptor complex.

PMID- 1398746
TI  - Production of rheumatoid factor in adoptively immune guinea-pigs after challenge
      with Treponema pallidum.
AB  - Guinea-pigs of inbred strains 2 and C4D were infused with various concentrations
      (1 x 10(8) to 4 x 10(8) of syngeneic nylon wool-purified Treponema pallidum
      immune T lymphocytes (TPI-T) and challenged 24 hr later with virulent T. pallidum
      (10(8) organisms). The degree of protection depended on the number of infused T
      cells and was associated with an accelerated production of IgM rheumatoid factor
      (RF). Fully protected animals (4 x 10(8) TPI-T) did not produce treponemal
      antibodies or circulating immune complexes (CIC) but produced IgM RF detectable
      10 days after infection. Partially protected animals (< or = 2 x 10(8) TPI-T)
      produced, 30 days post-infection, relatively low levels of treponemal antibodies
      but high levels of CIC and RF. Control animals infused with 2 x 10(8) TPI-T
      lymphocytes but not infected with T. pallidum, when monitored for a period of 6
      weeks, did not produce treponemal antibodies, CIC, or RF, excluding the
      possibility that IgM RF could be generated by the donor's B cells contaminating
      (circa 3%) the TPI-T lymphocytes. Moreover, unprotected syngeneic control animals
      infused, prior to infection, with T. phagedenis biotype Reiter-immune T cells or
      with T. pallidum-free testicular inflammatory fluid-immune T cells responded with
      increasing levels of treponemal antibodies; only a few animals produced RF and
      CIC 5 months after infection similarly to control guinea-pigs infected only. The
      production of RF in partially protected animals responding to infection with
      treponemal antibodies and CIC was apparently associated with the presence of the
      CIC; but the mechanism of RF production in fully protected animals in which no
      antibodies or CIC were detected is currently unknown.

PMID- 1398747
TI  - Kinetics of tumour necrosis factor and prostaglandin production by murine
      resident peritoneal macrophages as affected by dietary n-3 polyunsaturated fatty
      acids.
AB  - Cell-associated and secreted tumour necrosis factor (TNF), prostaglandin (PG) E2,
      and 6-keto PGF1 alpha were monitored at various times following in vitro
      stimulation of resident peritoneal macrophages with lipopolysaccharide (LPS).
      Macrophages were obtained from mice maintained on diets containing 1.5 wt% n-3
      polyunsaturated fatty acids (PUFA)+ 1.5 wt% n-6 fatty acids; 1.5 wt% n-6 fatty
      acids; or 3 wt% n-6 fatty acids, for 4 weeks. Cell-associated TNF increased
      transiently in the resident peritoneal macrophages from mice consuming all diets
      and decreased after TNF secretion had reached maximum and plateaued. Macrophages
      from mice consuming the n-3 PUFA contained more cell-associated TNF and secreted
      more TNF than macrophages from mice consuming diets containing n-6 fatty acids
      only, at all time-points studied. Macrophages from mice consuming the n-3 PUFA
      showed an earlier increase in cell-associated and secreted TNF compared with
      macrophages from mice consuming n-6 fatty acids only. Kinetics of maximum TNF
      production was not affected by the diets and dietary n-3 PUFA did not cause a
      prolonged increase in TNF secretion. Macrophages from mice consuming the n-3 PUFA
      produced less PG than macrophages from mice consuming the n-6 fatty acids only.
      PG secretion increased following appearance of cell-associated TNF but when PG
      had accumulated in the medium there was no further increase in TNF production.

PMID- 1398748
TI  - Adult T-cell leukaemia-derived factor/thioredoxin expression on the HTLV-I
      transformed T-cell lines: heterogeneous expression in ALT-2 cells.
AB  - Adult T-cell leukaemia (ATL)-derived factor (ADF), originally described as an
      inducer of interleukin-2 receptor-alpha (IL-2R alpha/Tac), has homology with the
      co-enzyme thioredoxin which is involved in many dithiol-dependent reducing
      processes. Using antibody against the C-terminal synthetic polypeptide of ADF and
      RNA probe of ADF, we examined the expression of ADF in various cell lines by
      immunofluorescence, immunohistochemical staining, Western blotting and in situ
      hybridization. ADF was intensely expressed on HTLV-I+ T-cell lines as compared
      with HTLV-I- T-cell lines. While the Epstein-Barr virus (EBV)+ B-lymphoblastoid
      cell lines were intensely positive for ADF, Burkitt-derived B cell line Jijoye
      with defective EBV was negative for ADF. Electron microscopic and
      photomicroscopic analysis of HTLV-I+ ATL-2 cells showed that ADF was localized on
      both the cell membrane and cytosol. In ATL-2 cells, a marked heterogeneity of ADF
      expression was observed. In in situ hybridization, heterogeneity of ADF messenger
      RNA (mRNA) expression was also demonstrated, indicating that ADF expression was
      regulated in the transcriptional level.

PMID- 1398749
TI  - Palmitic acid conjugation of a protein antigen enhances major histocompatibility
      complex class II-restricted presentation to T cells.
AB  - The effect on antigenicity of covalent attachment of lipid groups to a protein
      antigen was investigated. Coupling of palmitic acid to ovalbumin (OVA) enhanced
      major histocompatibility complex (MHC) class II-restricted presentation to most
      OVA-specific murine T-cell clones in vitro. The enhanced antigenicity of
      palmitoylated antigen was localized to the level of presentation of the synthetic
      peptide epitope, OVA 323-339. T-cell responses to palmitoylated antigen were more
      difficult to block with anti-MHC class II antibodies than responses to native
      antigen. However, T-cell proliferation to palmitoyl (p)-OVA and native (n)-OVA
      were blocked equally by anti-CD4 antibodies. Taken together, the results suggest
      that lipid conjugation of a protein antigen leads to the formation of a
      lipopeptide T-cell epitope with increased affinity of binding to MHC class II
      and/or T-cell receptor (TcR). These results have implications for the design of
      synthetic peptide vaccines.

PMID- 1398750
TI  - Identification of a human endothelial cell activation antigen that is co
      expressed by germinal follicle centre B lymphocytes.
AB  - Endothelial cell activation antigens may play important roles in immune responses
      and in inflammation. This report describes the identification and
      characterization of a monoclonal antibody, named EAA-B, which reacts specifically
      with human umbilical vein endothelial (HUVE) cells pre-treated with tumour
      necrosis factor-alpha (TNF-alpha) but not with untreated cells. The expression of
      the EAA-B antigen on HUVE cells could also be induced by interleukin-1 (IL-1),
      bacterial lipopolysaccharide (LPS), and phorbol esters but not by interferon
      gamma (IFN-gamma). By contrast, EAA-B antigen expression on neonatal foreskin and
      rheumatoid synovial fibroblasts, whether pre-treated with TNF-alpha or not, was
      not detectable. Peripheral blood leucocytes and the leukaemic cell lines U937, HL
      60, Raji and Molt 4 showed no detectable expression of the EAA-B antigen. Kinetic
      studies demonstrated that the EAA-B antigen was rapidly expressed, peaked at 6 hr
      and declined to basal level by 24 hr. Western blotting revealed that monoclonal
      antibody EAA-B recognized a polypeptide of approximately 80,000-90,000 MW. EAA-B
      partially blocked the augmented adhesion of HL-60 cells to TNF-treated HUVE
      cells. However, it failed to inhibit the enhanced binding of peripheral blood
      leucocytes, U937, Raji and Molt 4 Cells to TNF-treated HUVE cells. In situ, the
      EAA-B antigen was detected on some vascular endothelium in tonsils, lymph nodes,
      psoriatic skin and rheumatoid synovium but not in normal non-lymphoid tissues.
      Interestingly EAA-B antigen is also expressed by B lymphocytes in germinal
      follicle centres (GFC) of lymphoid tissues. The co-expression of this endothelial
      activation antigen by GFC B lymphocytes may have significant implications for
      immune responses and in B-lymphocyte differentiation.

PMID- 1398752
TI  - Lymphoid precursor cell lines have capacity to migrate to multiple lymphoid
      sites.
AB  - Cell lines have been isolated which phenotypically resemble natural killer
      (NK)/lymphoid precursor cells. These cell lines were derived by in vitro culture
      and represent continuously replicating cell lines. Since they do not grow as
      tumours in vivo, it was anticipated that they may have maintained the migratory
      capacity of their normal cell counterpart. Capacity to migrate to various
      lymphoid sites, i.e. spleen, bone marrow, thymus and mesenteric lymph node, has
      been analysed in a short-term 3-hr homing assay following intravenous injection
      of cells into a syngeneic irradiated host. Frequency of cells localizing in these
      organs was estimated by limit dilution cloning analysis. Three out of four cell
      lines were found to migrate to all four organs, while the C6VL/1 T-cell lymphoma
      was detected in spleen and bone marrow only, and did not enter thymus and
      mesenteric lymph nodes. This suggests that NK/lymphoid precursor cells may exist
      which have capacity to recirculate widely through the lymphoid system.

PMID- 1398751
TI  - Identification and tissue distribution of rabbit leucocyte antigens recognized by
      monoclonal antibodies.
AB  - Three monoclonal antibodies which recognize rabbit leucocytes have been
      characterized by immunofluorescence staining of a variety of cell populations and
      also by immunochemical techniques. The evidence obtained suggests that these
      antibodies recognize the rabbit equivalents of the CD58/LFA-3 (VC21),
      CD43/leukosialin (L11/135) and CD9 (MM2/57) antigens. A fourth antibody, RPN3/57,
      recognizes an antigen expressed strongly on T cells, thymocytes and neutrophils
      and at lower levels on platelets. It has not, however been possible to
      characterize the antigen recognized by RPN3/57 in molecular terms. Both L11/135
      and RPN3/57 are useful reagents for the detection of T cells both by flow
      cytometry and by immunohistochemistry.

PMID- 1398753
TI  - Regulation of leucocyte subpopulations in the sheep endometrium by progesterone.
AB  - To determine whether progesterone causes a change in lymphocyte subpopulations in
      the endometrium, frozen sections of intercaruncular and caruncular endometrium
      from ewes receiving daily i.m. injections of 100 mg/day progesterone were
      evaluated by immunohistochemistry for the presence of lymphoid cells bearing
      CD45, major histocompatibility complex (MHC) class II, CD45R, CD4 and CD8
      antigens. The pattern of lymphocyte distribution in the uterine endometrium of
      untreated ewes was similar to previous reports. Progesterone treatment,
      particularly after 60 days, caused reductions in numbers of CD45+ cells in the
      glandular epithelium and associated subepithelial stroma, MHC class II+ cells in
      all regions of the intercaruncular endometrium and CD45R+ cells in all epithelial
      regions of intercaruncular and caruncular endometrium. These data demonstrate a
      role for progesterone in regulating migration or proliferation of endometrial
      lymphocyte populations; this action of progesterone may represent an important
      mechanism by which progesterone modifies uterine immune function.

PMID- 1398754
TI  - The contribution of LFA-1 (CD11a/CD18) and MAC-1 (CD11b/CD18) to the in vivo
      migration of polymorphonuclear leucocytes to inflammatory reactions in the rat.
AB  - Recently the critical requirement for the CD18 family of adhesion molecules on
      leucocytes for their adhesion and migration to inflammatory reactions has been
      recognized in humans and several animal models. The in vivo studies have mostly
      utilized antibodies to CD18, the common beta-subunit of CD11a,b,c/CD18 molecules
      and thus have blocked the function of all three family members, making evaluation
      of the role of individual subunits impossible. Furthermore, none of the reagents
      used were suitable for studies in rats. Here we report the effects on
      polymorphonuclear leucocyte (PMNL) adhesion and in vivo migration of a new
      monoclonal antibody (mAb) TA3, which recognizes and blocks rat CD11a/CD18 (LFA
      1). These studies also evaluated mAb MRC OX42, which reacts with rat CD11b/CD18
      (CR3, MAC-1). Neither antibody alone inhibited rat PMNL adhesion to interleukin-1
      (IL-1)-activated rat endothelium, but the combination inhibited adhesion by 44%.
      OX42 treatment of rat PMNL inhibited phorbol myristate acetate (PMA) activated
      adhesion by 88%, while TA3 only inhibited this adhesion in combination with OX42,
      resulting in 99% inhibition of PMA-induced PMNL adhesion. Treatment of rats with
      TA3 alone partially inhibited 51Cr-labelled rat blood PMNL migration into zymosan
      activated serum (C5adesArg; ZAS), but not IL-1, or endotoxin [lipopolysaccharide
      (LPS)] induced dermal inflammatory reactions. MAb OX42 had no such effect in
      vivo. However, treatment with both antibodies virtually eliminated any PMNL
      accumulation in all three types of inflammatory reactions. Ex vivo treatment of
      the 51Cr-labelled PMNL, prior to i.v. infusion showed that mAb TA3 again
      preferentially inhibited PMNL migration to ZAS. These results suggest that in the
      rat, CD11a/CD18 plays a major role in PMNL migration to C5a and that either CD11a
      or CD11b/CD18 can function to maintain normal PMNL migration to IL-1 or LPS
      dermal inflammatory reactions. More than one member of this adhesion family or
      their ligands may need to be targeted for effective modulation of PMNL
      infiltration, at least in this species.

PMID- 1398755
TI  - Native and recombinant soluble CD23 fragments with IgE suppressive activity.
AB  - CD23-bearing cells are known to release 37,000 33,000 and 25,000 MW soluble CD23
      (sCD23) fragments that were reported to display multiple biological activities,
      including the potentiation of IgE synthesis. We previously reported that
      tunicamycin treatment of RPMI-8866 cells switched the biological activity of the
      sCD23 released by these cells from IgE potentiation to IgE suppression. In this
      study we show that tunicamycin-treated cells release small CD23 fragments with a
      MW of 16,000. These fragments are formed by truncation of the N-terminal 160
      amino acids and truncation of the carboxy-terminal end of CD23. Two observations
      indicate that the cleavage of surface CD23 into 16,000 MW fragments is not caused
      by tunicamycin-mediated inhibition of the N-glycosylation of CD23 but rather by
      the deletion of the carboxy terminal end of the molecule: (1) Chinese hamster
      ovary (CHO) transfectants expressing a CD23 mutant lacking the N-glycosylation
      site release 37,000-33,000 MW sCD23 unless they are treated with tunicamycin; (2)
      transfectants expressing a CD23 deletion mutant lacking the last 33 carboxy
      terminal amino acids release 16,000 MW sCD23. Highly purified native and
      recombinant 16,000 MW sCD23 bind to IgE and down-regulate the ongoing and the
      interleukin-4 (IL-4)-stimulated synthesis of IgE.

PMID- 1398756
TI  - Lymphocytes bearing the gamma delta T-cell receptor in acute toxoplasmosis.
AB  - Although the relative and absolute numbers of CD3+ cells (T lymphocytes) were
      similar in eight children with acquired Toxoplasma gondii infection and 10
      uninfected age- and sex-matched healthy controls, the proportion of cells bearing
      the gamma delta T-cell receptor was significantly higher in the subjects with
      acute toxoplasmosis. The great majority of gamma delta T cells from the infected
      patients expressed covalently bound gamma delta chains on their surface, i.e.
      were BB3+ lymphocytes. Since the gamma delta T-cell subsets exert both restricted
      and unrestricted major histocompatibility complex cytotoxicity, further research
      is needed to elucidate the role of gamma delta T cells in the control of this
      coccidian protozoan infection.

PMID- 1398758
TI  - Liposome potentiation of humoral immune response to lipopolysaccharide and O
      polysaccharide antigens of Brucella abortus.
AB  - Liposomes were evaluated for their effectiveness as vaccine carriers in the
      potentiation of the mouse humoral response to the lipopolysaccharide (LPS) and O
      polysaccharide (OPS) antigens of Brucella abortus. LPS and OPS were extracted
      from a pathogenic strain of B. abortus and were encapsulated within multilamellar
      vesicles. Groups of mice, immunized with liposome-encapsulated and free LPS or
      OPS, were bled weekly and the specific IgM and IgG levels in the sera were
      determined by an indirect fluorogenic enzyme-linked immunosorbent assay. Humoral
      response to these antigens were found to be dose-dependent. Mice immunized with
      LPS and OPS encapsulated within liposomes were found to have significantly higher
      IgG levels than mice immunized with free LPS and OPS. In addition, the antibody
      levels in mice that were immunized with liposome-encapsulated LPS and OPS were
      more sustained and remained at elevated levels--even after 5 weeks post
      immunization. As expected, OPS was found to be less immunogenic than LPS, but
      multiple injections of OPS encapsulated within liposomes greatly improved the
      immunogenicity. These results indicate that the humoral response to LPS and OPS
      of B. abortus can be enhanced when these antigens are encapsulated within
      liposomes.

PMID- 1398757
TI  - Abnormal TNF production in prediabetic BB rats is linked to defective CD45R
      expression.
AB  - The genetic basis and diabetes association of aberrant tumour necrosis factor
      alpha (TNF-alpha) production by activated peritoneal macrophages in diabetes
      prone (dp) biobreeding (BB) rats was analysed. Southern blot analysis could not
      detect a restriction fragment length polymorphism for the TNF gene distinguishing
      dp BB rats from Wistar (Wi) rats and diabetes resistant (dr) BB rats. The
      contiguous genetic arrangement of lymphotoxin (LT) and TNF genes described in
      mouse and man was also found in the rat by cloning a chromosomal region covering
      both genes. In search of a polymorphic marker we amplified a (CA)n:(GT)n
      microsatellite in the TNF promoter region by polymerase chain reaction (PCR). We
      detected two alleles, (CA)26 and (CA)33, but no correlation with diabetes risk
      was seen. Crosses between dp BB rats and Wi or Lewis. 1A (Lew. 1A) rats,
      respectively, indicated that aberrant TNF-alpha production of activated
      macrophages is inherited dominantly with only weak penetrance. Analysis of the F2
      generation and backcrosses with the two parental strains showed that aberrant TNF
      production co-segregates with lymphopaenia and defective CD45R expression,
      markers known to reflect a diabetes predisposing gene(s) outside the RT1 complex.
      We conclude that a single linkage group is responsible for both aberrant TNF
      production and defective T-cell maturation in dp BB rats.

PMID- 1398759
TI  - Control of Langerhans' cell density by a skin tumour-derived cytokine.
AB  - Langerhans' cells (LC) are bone marrow-derived dendritic antigen-presenting cells
      (APC) found in the epidermis of mammals. It is not known why they accumulate in
      the epidermis. Human and murine skin tumours are infiltrated with large numbers
      of LC, however previous experiments have shown that this does not seem to be
      associated with immune responses against the tumours. Here we show that a
      squamous-derived tumour cell line (T7) produces a cytokine which increases the
      number of LC in normal epidermis. T7 supernatant increased the density of LC in
      both mice syngeneic to the T7 cells (Skh:HR-1) as well as in BALB/c mice,
      indicating that the cytokine is not genetically restricted. The cytokine is a
      protein, not a prostaglandin, with a MW of > 12,000 as its production was
      inhibited by cycloheximide but not indomethacin and it could not be removed by
      dialysis against a 12,000 MW cut-off membrane. The increased numbers of LC found
      in tumour supernatant-treated epidermis expressed Ia as well as the molecule
      defined by the J11d monoclonal antibody, which is expressed by LC but not
      macrophages, confirming that these cells are LC. Another squamous-derived skin
      tumour, T79, which is not infiltrated with large numbers of LC when inoculated
      into syngeneic mice, did not produce a factor capable of increasing the density
      of LC. Hence these studies demonstrate either the activity of a novel cytokine or
      a new biological activity of a previously described cytokine. It is most likely
      that this cytokine increased the number of LC by attracting precursors into the
      epidermis. As the cytokine was produced by transformed squamous cells it is also
      possible that this cytokine is responsible for attracting LC into normal
      epidermis.

PMID- 1398761
TI  - Down-regulation of a spontaneous arthritis in male DBA/1 mice after
      administration of monoclonal anti-idiotypic antibodies to a cross-reactive
      idiotope on anti-collagen antibodies.
AB  - We recently described a spontaneously occurring, inflammatory and erosive joint
      disease in male DBA/1 mice. A major question is whether specific immune reactions
      are involved in eliciting this disease. The possibility that collagen
      autoimmunity might constitute one pathogenic factor was particularly interesting
      as this spontaneous arthritis appears to be genetically restricted in a way
      similar to collagen-induced arthritis. In the present study, we demonstrate
      increased serum antibody levels to collagen II in a fraction of the male DBA/1
      mice, but not in age-matched female controls. Administration of antibodies with
      an anti-idiotypic activity to anti-collagen II antibodies and with an affinity
      for determinants present on isolated syngeneic IgG Fc but not on intact IgG, was
      shown to interfere with the development of the spontaneous arthritis in a manner
      similar to that earlier documented for collagen arthritis. These observations
      suggest that mechanisms similar to those operating in collagen-induced arthritis
      may also be found in the spontaneously occurring arthritis in male DBA/1 mice.

PMID- 1398760
TI  - Characterization of human mast cells developed in vitro from fetal liver cells
      cocultured with murine 3T3 fibroblasts.
AB  - Cocultures of dispersed human fetal liver cells with murine Swiss 3T3 fibroblasts
      resulted in the development of human mast cells after 1 to 4 weeks of culture.
      Mast cells were detected by immunohistochemistry using a murine monoclonal anti
      tryptase antibody, before metachromasia appeared with toluidine blue. When
      subjected to double immunohistochemistry using murine monoclonal anti-chymase and
      anti-tryptase antibodies, 94% +/- 10% (SD) of the mast cells seen at day 30 of
      culture were of the MCT type. These results contrast with those obtained with
      human mast cells derived from cord blood mononuclear cells cocultured with murine
      3T3 fibroblasts which are comprised of substantially greater numbers of MCTC
      cells, averaging 48% +/- 31% (SD) at day 30 of culture. Mast cells developed in
      vitro from fetal liver cells or cord blood mononuclear cells contained similar
      amounts (+/- SD) of histamine (0.9 +/- 0.5 pg/cell and 1.1 +/- 1 pg/cell,
      respectively) and tryptase (1.7 +/- 0.4 pg/cell and 1.9 +/- 1.2 pg/cell,
      respectively) on day 30 of culture. Fetal-liver-derived mast cells from a 30-day
      old culture were identified by immunoelectron microscopy using gold-labelled
      antitryptase antibody. Typically, these mast cells appeared immature as they had
      large nuclear to cytoplasmic ratio and a small number of ill-formed cytoplasmic
      granules. For both fetal-liver- and cord-blood-derived mast cells, there was no
      evidence of conversion of the MCT type into the MCTC type provided by this study.
      These results suggest that commitment to develop as an MCT or MCTC type of mast
      cell may have occurred in mast cell precursors present in fetal liver and cord
      blood mononuclear cells, prior to granulation.

PMID- 1398762
TI  - Neutrophil priming by hepatocyte growth factor, a novel cytokine.
AB  - We demonstrate here that the recently defined cytokine hepatocyte growth factor
      (HGF) 'primes' human neutrophils. Recombinant human HGF over the concentration
      range 0.1-20 ng/ml increased the neutrophil response to f-met-leu-phe by up to
      200%, and required only a short preincubation, 10 min producing the maximum
      effect. Priming was independent of changes in cytosolic-free calcium homeostasis.
      We conclude that HGF may be a physiologically important cytokine with 'priming'
      activity for neutrophils.

PMID- 1398763
TI  - Development and characterization of a monoclonal antibody specific for the bovine
      low-affinity interleukin-2 receptor, BoCD25.
AB  - An IgM monoclonal antibody, UC-2C2 was produced using splenocytes from mice
      immunized with cultures of interleukin-2 (IL-2)-dependent bovine peripheral blood
      lymphocytes. UC-2C2 was found to recognize a cell surface antigen of apparent
      molecular weight 52,000-54,000 present on activated bovine peripheral blood
      mononuclear leucocytes (PBML) but not on resting PBML or cells of the bovine
      lymphoblastoid cell line BL3. The 52,000-54,000 MW antigen was expressed early
      following activation of PBML by mitogens or alloantigens, with the majority of
      cells positive by 48 h of culture. UC-2C2 was unable to block binding of
      phycoerythrin (PE)-conjugated human recombinant IL-2 to PHA-stimulated bovine
      PBML as determined by flow cytometric analysis. However, two-colour analyses
      indicated that the antigen recognized by UC-2C2 was present on the same cell
      population that expressed IL-2 receptors. All activated T lymphocytes of BoCD4,
      BoCD8 and gamma delta receptor positive phenotypes expressed the target antigen
      of UC-2C2 and IL-2 receptors. Monocytes and B lymphocytes expressed the target
      antigen of UC-2C2 and IL-2 receptors at a lower density. This differential
      expression by the various PBML subpopulations parallels that described for
      expression of the low-affinity IL-2 receptor (CD25) on human leucocyte
      subpopulations. Based upon the relative molecular weight, time-course of
      expression and cellular distribution of the antigen identified by UC-2C2, it is
      inferred that UC-2C2 recognizes an epitope on the bovine homologue of CD25 which
      is not involved in binding IL-2.

PMID- 1398764
TI  - Interactions between interleukin-2-activated lymphocytes and vascular
      endothelium: binding to and migration across specialized and non-specialized
      endothelia.
AB  - A prerequisite for the successful immunotherapy of solid tumours with interleukin
      2 (IL-2)-activated lymphocytes is their ability to home to the tumour tissue.
      Lymphocyte homing is a complex process which is known to involve at least two
      independently regulated events: adhesion to the luminal surface of vascular
      endothelium and the subsequent transendothelial migration of lymphocytes. In this
      study we have used an in vitro model of lymphocyte homing which employs
      specialized high endothelium to ask whether IL-2-activated lymphocytes are able
      to migrate across vascular endothelium in order to leave the blood vessel. Both
      the adhesion of IL-2-activated cells and their migration across monolayers of
      cultured high endothelial cells (HEC) were increased in comparison with non
      activated lymphocytes. The adhesion of IL-2-activated lymphocytes was mediated by
      lymphocyte function-associated antigen-1 (LFA-1) and a very late activation
      antigen-4 (VLA-4)-related pathway. LFA-1-dependent adhesion was mediated by
      ligands on HEC other than the intercellular adhesion molecule-1 (ICAM-1) and the
      VLA-4-related pathway was mediated by ligands other than the CS1 domain of
      fibronectin. HEC-adherent lymphocytes were enriched in natural killer (NK) cells
      and CD8+ T cells which are known to be the tumour-cytotoxic cells in IL-2
      activated lymphocytes. However, there was no evidence of cytotoxicity towards the
      endothelial layer using a syngeneic model. The interaction of IL-2-activated
      lymphocytes and endothelial cells was not specific for high endothelium since
      equal numbers of activated lymphocytes bound to and migrated across aortic
      endothelium. The inability of IL-2-activated lymphocytes to discriminate between
      high endothelium and non-specialized 'flat' endothelium could be responsible for
      the widespread dissemination of the cells throughout the body following their
      adoptive transfer and the unwanted side-effects at non-involved sites.

PMID- 1398765
TI  - Inhibition of CD25 (IL-2R alpha) expression and T-cell proliferation by
      polyclonal anti-thymocyte globulins.
AB  - Anti-lymphocyte and anti-thymocyte globulins (ATG) are currently used as
      immunosuppressive agents in organ transplantation. Their administration in vivo
      may induce not only lymphocyte depletion but also functional effects which were
      investigated in the present study. In vitro ATG inhibited T-cell proliferation
      induced by monocyte-dependent T-cell mitogens, like CD3 antibodies,
      phytohaemagglutinin (PHA) and concanavalin A (Con A), by monocyte-independent
      mitogens, like CD2 antibodies, or by protein kinase C activators (phorbol esters)
      associated with a calcium ionophore. The inhibitory effect of ATG was therefore
      not solely accounted for by a suppression of co-stimulatory signals delivered by
      monocytes, but rather implied a direct action on T cells. Addition of recombinant
      human interleukin-2 (rIL-2) did not overcome the inhibition. Suppression of T
      cell proliferation by ATG was characterized by normal RNA synthesis and IL-2
      secretion contrasting with markedly reduced expression of the CD25 protein [p55,
      the alpha-chain of interleukin-2 receptor (IL-2R)] both in cytoplasm and on T
      cell membrane, as well as a decreased secretion of interferon-gamma (IFN-gamma).
      Northern blot analysis revealed increased levels of CD25 and IFN-gamma mRNA,
      suggesting a post-transcriptional inhibition of these molecules, whereas IL-2
      mRNA levels were unchanged. These data demonstrate that inhibition of T-cell
      proliferation by ATG can be attributed primarily to a post-transcriptional defect
      of CD25 expression, implying a novel mechanism different from those described
      with other immunosuppressive agents. Blocking of T-cell proliferation in the late
      G1 phase of the cell cycle may contribute to the immunosuppressive activity of
      ATG in prophylactic treatment of allograft rejection.

PMID- 1398766
TI  - Transforming growth factor-beta enhances interleukin-6 secretion by intestinal
      epithelial cells.
AB  - Recent reports have suggested that transforming growth factor-beta (TGF-beta) may
      have an important role in IgA immune responses, e.g. induction of surface IgM+ B
      cells to commit to IgA. TGF-beta is also an important regulatory cytokine for the
      maturation of intestinal epithelial cells. Using the IEC-6 rat intestinal
      epithelial cell line as a model system, TGF-beta 1 was found to enhance
      interleukin-6 (IL-6) secretion by the IEC-6 cells. The IL-6 was produced in a
      dose-dependent manner and secretion could be specifically inhibited by an anti
      TGF-beta 1 antibody. IL-6 production by the IEC-6 cells was confirmed by using a
      rabbit anti-mouse IL-6 antibody which completely neutralized the IL-6 present in
      the IEC-6 cell supernatant. The enhancement of IL-6 secretion was found to
      involve a low-level enhancement in the expression of RNA for IL-6. The induction
      of IL-6 secretion was also reversible when TGF-beta was removed. These results
      suggest that the action of TGF-beta on intestinal epithelial cells may play an
      important role in immune responses at the intestinal mucosa.

PMID- 1398767
TI  - Histological and functional differentiation of non-lymphoid cells in the chicken
      spleen.
AB  - The phenotypes and functions of various populations of non-lymphoid cells in the
      chicken spleen were investigated with monoclonal antibodies and after in vivo
      administration of antigens. Monoclonal antibody CVI-ChNL-68.1 was used to detect
      red pulp macrophages, interdigitating cells, and monocytes, whereas CVI-ChNL-68.2
      was used to detect ellipsoid-associated non-lymphoid cells (EANC). Two new
      monoclonal antibodies were developed: CVI-ChNL-74.2, which specifically
      recognized red pulp macrophages and a ring of macrophages surrounding the peri
      ellipsoid lymphocyte sheath; and CVI-ChNL-74.3, which specifically recognized
      follicular dendritic cells (FDC) in germinal centres and small clusters of
      stromal cells in T-cell areas. After intravenous injection of lipopolysaccharide
      (LPS), the number of 68.1+ and 74.2+ macrophages decreased dramatically, whereas
      68.2+ EANC and 74.3+ FDC were unaffected. After intravenous injection of heat
      inactivated Brucella abortus, the numbers of both macrophages and EANC decreased.
      In contrast, a significant increase of 74.3+ cells was observed in the T-cell
      areas outside the germinal centres. As expected, intravenous injection of non
      mitogenic antigens, such as keyhole limpet haemocyanin and Ficoll, and
      carrageenan did not affect the non-lymphoid cell populations. At least six
      subpopulations of non-lymphoid cells in the chicken spleen can now be
      discriminated with monoclonal antibodies. Our results show that mononuclear
      phagocytes are sensitive for mitogenic stimulators such as LPS and Brucella
      abortus. In contrast, stromal non-lymphoid cells are only sensitive to the
      particulate mitogen Brucella abortus. We conclude that the complex formed by
      ellipsoid cells, the peri-ellipsoid B-cell sheath, and the surrounding
      macrophages, is the functional equivalent of the mammalian marginal zone.

PMID- 1398768
TI  - The role of antigen-presenting cells in the regulation of delayed-type
      hypersensitivity. I. Spleen dendritic cells.
AB  - A previously unreported mechanism for the induction of delayed-type
      hypersensitivity (DTH) was studied in detail. The subcutaneous injection (without
      adjuvant) of spleen dendritic cells (DC) pulsed with keyhole limpet haemocyanin
      (KLH) into syngeneic BALB/c mice caused DTH when the ear was later injected with
      the same antigen. When KLH-pulsed DC were transferred intravenously, DTH was not
      induced, although the titre of anti-KLH antibodies rose after such transfer. The
      intravenous transfer of KLH-pulsed DC into mice immunized subcutaneously with KLH
      in complete Freund's adjuvant (CFA) at the same time (in the sensitization
      phase), but not when the ear was challenged with KLH (in the effector phase), had
      a suppressive effect on DTH, in an H-2-restricted way. When radiolabelled DC were
      transferred intravenously, they migrated into the spleen, but when transferred by
      subcutaneous injection, they stayed in the skin or migrated into the lymph nodes.
      In splenectomized mice immunized with KLH, the intravenous transfer of KLH-pulsed
      DC did not cause production of anti-KLH antibodies and did not suppress DTH.
      These findings suggest that the anatomical sites in which antigens are presented
      (i.e. the spleen or lymph nodes) rather than the type of cell that first presents
      antigens to the immune system governs whether DTH or antibody production is
      induced. Antibody production was induced when antigens were presented in the
      spleen.

PMID- 1398769
TI  - Modulation of thymocyte subsets during acute and chronic phases of experimental
      Trypanosoma cruzi infection.
AB  - Several observations have demonstrated the importance of T-cell-mediated
      mechanisms in experimental Chagas' disease. In previous studies, we have shown
      that mice acutely infected by Trypanosoma cruzi develop a progressive thymic
      atrophy with severe alterations in the lymphoid compartment. In this report we
      performed a kinetic analysis of the murine thymic lymphocytes comparing acute and
      chronic phases of infection. At the chronic phase, we observed that total
      thymocyte numbers returned to age-matched control values. Additionally, the
      decrease in the percentage of CD4+CD8+, in parallel with an increase of CD4+CD8-,
      CD4-CD8+, CD3high, TcR alpha beta and TcR gamma delta cells detected in the acute
      infection, was also restored in chronically infected mice. This thymocyte
      recovering is probably linked to the increase in the percentage of thymocyte
      precursors, such as CD4lowCD8- and CD4-CD8low cells, together with the increase
      in the number of IL-2R+ and cycling cells, appearing in the late stages of acute
      infection.

PMID- 1398770
TI  - A role for tumour necrosis factor-alpha in the human mixed lymphocyte culture
      reaction.
AB  - The possible role and influence of tumour necrosis factor-alpha (TNF-alpha) in
      the human mixed lymphocyte culture (MLC) reaction was investigated. Polyclonal
      rabbit sera to recombinant human-TNF-alpha (rhTNF-alpha) consistently inhibited
      the MLC, and this could be reversed by simultaneous addition of rhTNF-alpha to
      the culture medium. Under optimal cell culture conditions, the exogenous addition
      of 1000 U/mL of rh TNF-alpha had a variable but generally small enhancing effect
      on the MLC reaction. Additional studies have clearly highlighted the importance
      of MLC assay conditions in influencing the effect of exogenous rhTNF-alpha.
      Enhancement of the MLC reaction was only consistently observed under suboptimal
      cell culture conditions. While the present study clearly supports an important
      role for TNF in controlling the proliferative response in the human MLC reaction
      it also highlights the influence of in vitro tissue culture conditions in
      determining the effect of exogenous TNF-alpha in this assay.

PMID- 1398771
TI  - Alistair Cunningham and the generation of antibody diversity after antigen.

PMID- 1398772
TI  - The dynamics of T cell-dependent B cell responses in vivo.

PMID- 1398773
TI  - Defining the nucleic acid substrate for somatic hypermutation.
AB  - Recent reports have more precisely defined the distribution of somatic mutations
      around rearranged mouse V-D-J genes. The 5' boundary of mutation is most likely
      in the region of the transcription start site (cap) and/or the promoter (P),
      implying that transcription may be a prerequisite for mutations to be generated.
      As more than 95% of somatic mutations lie downstream of the cap site, the
      transcription unit itself is implicated as the target of the mutational
      machinery. For heavy chain genes, the 3' boundary can extend into the enhancer
      region (E). For kappa light chain genes, the 3' boundary extends to approximately
      700 bp beyond J kappa-5 (approximately 700 bp upstream of E). In a single study
      on mutated derivatives of the rearranged mouse lambda 1 light chain V-J gene, it
      was claimed that the 3' boundary fell within the constant region (C) exon.
      Although more data are required, the frequency of mutations around V-D-J genes
      appears asymmetrical, being positively skewed with a single mode centred near the
      V-D-J coding region and a long tail extending into the 3' non-translated region
      of the J-C intron. Such a distribution may place constraints on possible
      molecular mechanisms. It is suggested that the apparent asymmetrical pattern of
      mutation is best explained by models that assume localized error-prone DNA
      synthesis generating variable fragment lengths of mutated DNA or cDNA
      retrotranscripts. The frequency distribution of these lengths of mutated DNA is
      positively skewed into the 3' J-C intron, with a common terminus at or near the
      cap site. It is then assumed that they can be integrated into the target V-D-J
      region via a gene conversion or homologous recombination process. The model
      invoking reverse transcription may be preferred as it best explains the data
      without too many ad hoc assumptions.

PMID- 1398774
TI  - In situ studies of the antigen-driven somatic hypermutation of immunoglobulin
      genes.

PMID- 1398775
TI  - The mechanism of T and B cell collaboration.

PMID- 1398776
TI  - Expression of the high responder/non-responder human Fc gamma RII. Analysis by
      PCR and transfection into FcR-COS cells.
AB  - Distinct differences in the capacity of monocyte Fc gamma RII of different
      individuals to bind or not bind mouse IgG1 defines a polymorphism of Fc gamma
      RIIa and has previously been defined as the high responder (HR) or low responder
      (LR) polymorphism of Fc gamma RII. The precise definition of the molecular basis
      of the human HR/LR polymorphism of Fc gamma RIIa from the peripheral blood
      mononuclear cells of normal individuals has been determined by anti-CD3 induction
      of T cell proliferation, the polymerase chain reaction (PCR), nucleotide
      sequencing, transfection and IgG binding. Amplification of first strand cDNA from
      mRNA isolated from mononuclear cells was performed by PCR using primers specific
      for the sequences encoding the leader and cytoplasmic sequences of PCR using
      primers specific for the sequences encoding the leader and cytoplasmic sequences
      of Fc gamma RIIa, which is normally expressed in monocytes. Sequencing of the PCR
      products and transfection of these to Fc gamma R- cells indicated that in Fc
      gamma RIIa of HR or LR individuals: (i) three nucleotide substitutions (CA to TG
      and G to A) resulted in the change of glutamine to tryptophan at position 27
      (first extracellular domain) and arginine to histidine at position 131 (second
      extracellular domain); (ii) expression of cDNA encoding the various combinations
      of these indicated that arginine at position 131 was essential for IgG1 binding
      whereas the amino acid changes at position 27 had no effect; and (iii) IgG1 at
      high concentration bound to all allomorphic forms of Fc gamma RIIa.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1398777
TI  - Pattern of the action of a suppressor factor produced by a human macrophage-like
      cell line, U937.
AB  - A U937 suppressor factor (U937SF) was purified from crude supernatant by
      sequential chromatography using fast protein liquid chromatography. The molecular
      weight and isoelectric point of U937SF were 69 kDa and 4.5, respectively. The
      U937SF preparation inhibited the proliferative response in human PBMC stimulated
      with an antigen tuberculin purified protein derivative, tetanus toxoid) or a
      mitogen (phytohaemagglutinin concanavalin-A). U937SF depressed both interleukin-2
      (IL-2) production and IL-2 receptor (CD25) expression in peripheral blood
      mononuclear cells (PBMC) stimulated with an antigen but not with a mitogen. Anti
      CD3 monoclonal antibody-induced responses including a proliferative response, IL
      2 production and CD25 expression were suppressed by U937SF. In contrast, U937SF
      did not affect monocyte functions such as antigen processing and IL-1 production.
      Neither did it modulate the expression of T cell receptor (TCR) or CD3 molecules
      on the surface of lymphocytes. Moreover it did not inhibit CD25 expression in
      PBMC stimulated with phorbol myristate acetate plus A23187. These results suggest
      that U937SF prevents both IL-2 production and CD25 expression in lymphocytes
      activated through the TCR/CD3, but not through the other receptors or molecules.
      In addition, U937SF does not block the early activation events following TCR
      mediated stimulation, nor affect the pre-TCR activation steps.

PMID- 1398778
TI  - Immunomodulatory activity of a peptide isolated from Viscum album extract (NSC
      635 089).
AB  - A peptide isolated from Viscum album extract (Iscador) has been earlier reported
      to have cytotoxic and tumour reducing activity. Administration of the peptide (2
      micrograms/ml) was found to produce increased natural killer cell activity (NK
      activity) in the normal animals and tumour bearing animals. The peak activity was
      observed on the 3rd day after the administration of the peptide. Administration
      of the peptide also stimulated antibody dependent cellular cytotoxicity (ADCC)
      which was expressed maximally on the fourth day. There was also an increase in
      antibody forming cells in the spleen, and antibody titers were increased in the
      animals treated with the peptide. Activity of the crude plant extract coincided
      with the activity of the peptide, indicating that the isolated peptide is mainly
      responsible for the immunostimulatory activity present in Viscum album extract.

PMID- 1398779
TI  - Human lymphocyte stimulation by legume lectins from the Diocleae tribe.
AB  - Lectins from eight leguminous seeds from the Diocleae tribe were compared to
      Concanavalin A (Con A), a well known T cell mitogen, on the stimulation of
      lymphocyte proliferation and Interferon gamma (IFN-gamma) production by
      peripheral blood mononuclear cells (PBMC) from normal volunteers. Lectins from
      Canavalia brasiliensis and Dioclea virgata induced the highest lymphocyte
      proliferation, both much higher than levels obtained with Con A, whereas lectins
      from Dioclea guianensis var. lasiophylla and from Canavalia bonariensis induced
      the lowest stimulation. Lectins from Dioclea rostrata, D. grandiflora, D.
      violacea and Cratylia floribunda induced intermediate levels of proliferation.
      The highest stimulation for IFN-gamma production was obtained with the lectin
      from D. rostrata, followed by those of C. floribunda and C. brasiliensis; only
      the lectins from D. virgata and C. bonariensis induced an IFN-gamma production
      lower than the one obtained by Con A-stimulation. Since all these legumes belong
      to the same tribe of C. ensiformis (Con A), and all are supposed to exhibit very
      similar lectins, it is interesting the high variation in the stimulation of
      lymphocyte proliferation. It is also noteworthy the dissociation between this
      parameter and IFN-gamma production in the case of D. virgata. A detailed analysis
      on the structure of such lectins, and their ligand sugars on lymphocyte surface
      is necessary to further explore such differences.

PMID- 1398780
TI  - Dysregulated proteolysis in AIDS.
AB  - Plasmin activity induced by different concentrations of added urokinase (UK) in
      serum from 20 patients with AIDS (P) and 10 healthy control (HC) subjects was
      measured using the fibrin plate assay. 125I-fibrin coated 24 well plates were
      exposed to UK (0.34-6.8 ng/ml) or to trypsin (T) (2.5 micrograms/ml) in the
      presence of serum (10%) from P or HC. Control wells were exposed to either T or
      tris buffer (pH 8.1) alone. Volumes were adjusted to 1 ml with buffer and after 1
      hr at 37 degrees C, radioactivity (cpm) released into the medium was determined
      using a gamma counter. Data are expressed as % plasmin activity or as %
      inhibition of plasmin activity. All sera from HC totally abrogated (greater than
      98%) the plasmin activating ability of UK (1.7 ng/ml). In contrast, sera from
      approximately 50% of P were less able to inhibit plasmin activation (to 26%). The
      inability of P sera to inhibit plasmin activation was specific since P and HC
      sera were equally capable of inhibiting T. Mixing experiments using P and HC sera
      demonstrated that P sera did not block the ability of HC sera to inhibit plasmin
      activation. The inhibitory activity of HC and active P sera eluted in the void
      volume of a spehadex G100 column (MW greater than 100,000 daltons) and is acid
      sensitive, however HC sera also contains an acid stable inhibitor(s) of plasmin
      activation not detected in P sera. These data suggest dysregulation of UK
      dependent proteolysis may be associated with AIDS.

PMID- 1398781
TI  - Profile of cytokines in synovial fluid specimens from patients with arthritis.
      Interleukin 8 (IL-8) and IL-6 correlate with inflammatory arthritides.
AB  - The synovial fluid aspirated from patients with symptomatic arthritis was
      analyzed for the presence of tumor necrosis factor (TNF), interleukin 6 (IL-6)
      and interleukin 8 (IL-8). All three cytokines were found in both inflammatory and
      non-inflammatory arthritides: IL-8 levels ranged from less than 20 to 38,990
      pg/ml, IL-6 from less than 10 to 72,300 pg/ml and TNF from less than 4 to 61
      pg/ml. No inhibitors of cytokine activity were found. IL-8 and IL-6 were present
      in significantly higher levels in patients with inflammatory arthritis compared
      to patients with osteoarthritis, and there was significant correlation between
      the IL-6 and IL-8 levels. These findings document the presence of multiple
      cytokines in the synovial fluid specimens of patients with arthritis, and
      demonstrate that higher cytokine levels accompany inflammatory arthritis.

PMID- 1398782
TI  - The effect of divalent metal ions on the thermostability of C3.
AB  - Thermostability studies on human complement component C3 showed that saturation
      of the electronegative sites in the C3 molecule with divalent cations offered
      some protection against heat denaturation, a finding not previously reported in
      the literature. To inactive C3 in about 30 minutes, the required temperature was
      61 degrees C in the presence of excess Ca2+ ions, 59.5 degrees C in the presence
      of excess of Mg2+ ions, but only 54 degrees C in the absence of these ionized
      metal ions.

PMID- 1398784
TI  - Effectiveness of an oral enteric coated vibrio vaccine for use in salmonid fish.
AB  - An oral enteric-coated Vibrio anguillarum vaccine was developed by initially
      coating lyophilized bacteria onto 0.9 mm diameter dextrose sugar beads followed
      by an Eudragit L-30D coat to serve as enteric protection. Vaccine efficacy was
      determined by both an in vivo challenge with live pathogen and measurements of
      serum and mucus antibody levels by ELISA. Survival rates after challenge were
      80.3%, 83.3% and 70.3% among the vaccine group, positive and negative controls
      respectively. Serum and mucus antibody levels were found to be significantly
      greater in the vaccine group (p less than 0.01). In cases where equivalent
      survival among tested groups is observed, determination of antibody titer by
      ELISA may be a preferable indicator of vaccine efficacy.

PMID- 1398783
TI  - Negative regulation of interleukin-1 in immune reactive cells.
AB  - Interleukin-1 (IL-1) is an immunological regulator with a multitude of effects.
      Recently, IL-1 inhibitors from urine, monocytes, or monocytic cell lines have
      been described. We previously demonstrated an IL-1 inhibitor from human monocytes
      under immune complex or immunoglobulin stimulation. The present studies were
      initiated to determine the production of IL-1 inhibitor from human
      polymorphonuclear cells (PMN), B and T lymphocytes in response to certain stimuli
      using a murine thymocyte system responsive to IL-1. My results indicated that the
      inhibitor is constitutively present in PMN because unstimulated PMN supernatants
      also show inhibitory activity. B and T lymphocytes can not produce IL-1 inhibitor
      under zymosan, immunoglobulin, or immune complex stimulation. The presence of
      this PMN inhibitor may also be important in the negative regulation of IL-1.

PMID- 1398785
TI  - Augmentation of natural cell-mediated cytotoxic activity by supernatant from in
      vitro mitogen-stimulated, in vivo hormone-treated lymphocytes in immature male (K
      strain) chickens.
AB  - Newly hatched White Leghorn male chicks were used in this study. Triiodothyronine
      (T3; 0.1 or 1 ppm) and Thyrotropin Releasing Hormone (TRH; 1 or 5 ppm) were added
      to the feed for an 8-week period starting at hatch. A fifth group received the
      unsupplemented diet and served as controls. Peripheral blood lymphocytes from
      each treatment group were cultured in vitro with or without different mitogens
      (PHA, Con-A, or LPS), and the culture supernatants were tested for the presence
      of lymphokines (LK). The natural cell-mediated cytotoxicity (NCMC) assay was
      carried out with or without supernatant using the standard chromium (Cr51)
      release assay. Control untreated chicks were used as donors for effector cells
      and the P815 mouse mastocytoma was used as a target. Supernatant from in vivo 1
      ppm T3- or 5 ppm TRH-treated lymphocytes significantly suppressed NCMC (or cells
      mediating NCMC, e.g., NK cells). However, supernatant from 1 ppm T3-treated, PHA
      stimulated lymphocytes significantly enhanced NK cells cytotoxicity, while
      supernatant from 5 ppm TRH-treated lymphocytes with PHA stimulation tended to
      suppress cytotoxicity. These results provide evidence supporting a regulatory
      role of the hypothalamo-pituitary thyroid axis on lymphokine (LK) production. The
      results also suggest that these hormones act on different subpopulation of
      lymphocytes, and therefore, the mediators released by them.

PMID- 1398786
TI  - An autopsy study of relationship between perinatal stomach capacity and birth
      weight.
AB  - BACKGROUND: Aspiration pneumonia is a common complication of overfeeding in
      neonates. Since overfeeding may be related to neonatal stomach capacity, it was
      considered worthwhile to obtain such data. AIMS: To measure the capacity of
      stomach obtained from fresh stillbirths and liveborn infants at autopsy and
      correlate the same with their birth weights. METHODS: Stomach capacity was
      measured at autopsy in 63 stillborn and 37 newborn infants with birth weights
      ranging from 500 g to 3500 g. RESULTS: Stomach capacity had a significant
      positive correlation with birth weight (r = 0.56, p < 0.001). A formula and a
      nomogram have been derived to estimate stomach capacity from birth weight. There
      was no significant difference in stomach capacity between liveborn and stillborn
      infants in any of the weight groups, except in the 1501-2000 g weight group (p <
      0.001). CONCLUSIONS: Our results have provided normative data on stomach capacity
      across a wide birth weight range in the perinatal period.

PMID- 1398787
TI  - Transjugular intrahepatic portacaval shunts (TIPS).

PMID- 1398788
TI  - Sodium and potassium content of liquid antacids.
AB  - Sodium and potassium contents of 37 commercially available liquid antacid
      preparations were estimated. Only nine preparations had sodium content below 60
      mmol/L. The potassium content was below 1 mmol/L in 26 preparations. We conclude
      that caution should be exercised in selecting liquid antacid preparations in whom
      critically ill patients for electrolyte overload could prove harmful.

PMID- 1398790
TI  - Unusual gall bladder perforation--definition of a new type.

PMID- 1398789
TI  - Effect of blockade of transdiaphragmatic absorption of bacteria on survival in
      peritonitis: an experimental study in rats.
AB  - An experimental rat model of established peritonitis was used to test the effect
      of intraperitoneal injection of platelet rich plasma (PRP) on blood and
      peritoneal fluid culture positivity and survival rates. Thirty animals divided
      into two groups of 15 each were studied. The first group served as control while
      animals in the second group received intraperitoneal injection of PRP. The use of
      PRP in established. Peritonitis was of no significant benefit.

PMID- 1398791
TI  - Gluteal fistula--an unusual manifestation of carcinoma colon.
AB  - A case of carcinoma cecum presented as a gluteal enterocutaneous fistula. Tumor
      excision provided effective palliation for nearly three years.

PMID- 1398792
TI  - Transmural bowel infarction: a rare complication of aortic dissection.
AB  - A 50 year old hypertensive man presented with acute epigastric pain associated
      with massive gastrointestinal bleed and died within 48 hours of admission.
      Autopsy revealed transmural infarction of the gut due to a long aortic
      dissection.

PMID- 1398794
TI  - Large single candidal liver abscess treated with aspiration and antifungal drugs.

PMID- 1398793
TI  - Benign non-traumatic inflammatory stricture of the common bile duct.
AB  - A case of isolated benign non-traumatic inflammatory stricture of the mid portion
      of the common bile duct presenting with recurrent jaundice and cholangitis is
      reported. The histological features suggested that this was not due to sclerosing
      cholangitis.

PMID- 1398795
TI  - Primary malignant hemangioendothelioma of jejunum.
AB  - Primary malignant hemangioendothelioma is a rare tumor. We report a patient with
      a malignant jejunal hemangioendothelioma which had metastasized to the regional
      lymph nodes and the liver.

PMID- 1398796
TI  - Prepancreatic preduodenal portal vein.
AB  - We report a 17 year old girl with prepancreatic and preduodenal portal vein. She
      presented with recurrent vomiting. Barium study revealed malrotation of the gut.
      Laparotomy confirmed malrotation of the gut with a prepancreatic and preduodenal
      portal vein. The patient is asymptomatic after gastrojejunostomy and vagotomy.

PMID- 1398797
TI  - Endoscope disinfection: are the referees watching?

PMID- 1398798
TI  - On training and testing in gastroenterology.

PMID- 1398799
TI  - Colopathy in portal hypertension.

PMID- 1398800
TI  - Oral 4-ASA in ulcerative colitis.

PMID- 1398801
TI  - Genetics of cholera toxin.
AB  - Cholera is caused by the toxin secreted by Vibrio cholerae 01. Cholera toxin (CT)
      is a protein consisting of A and B subunits. The former contributes to
      intracellular toxicity whereas the B subunit is required for binding of CT to
      eukaryotic cell surface receptor. The structural genes encoding A and B subunits
      are designated as ctxA and ctxB respectively. These genes are located on the
      chromosome forming an operon in which ctxA precedes ctxB. The ctxAB have been
      cloned and sequenced. Classical strains contain two full copies of unlinked
      ctxAB. Most el tors have single copy. However, in some strains there are two
      copies which are arranged in tandem. The tandem duplication and amplification of
      ctxAB is controlled by a transposable element like DNA sequence called RS1. A
      number of genes have been identified which regulate the expression of ctx operon.
      V. cholerae seems to elaborate more than one toxin which are different from the
      one encoded by ctxAB genes.

PMID- 1398802
TI  - Serum beta 2 microglobulin levels in HIV seropositive persons.
AB  - As beta 2 microglobulin (B2M) has been found to be elevated in immunological
      disorders and also in HIV infection, its levels were studied in 475 HIV
      seropositive, asymptomatic persons; 101 HIV seronegative persons from high risk
      groups for HIV and 99 healthy controls. The B2M levels in asymptomatic HIV
      seropositives are found to be significantly higher than healthy controls (1.0
      mg/1 to 2.7 mg/1, P less than 0.001) and HIV seronegatives from high risk groups
      (1.1 mg/1 to 2.7 mg/1, P less than 0.001). Two hundred and thirty four (49.26%)
      seropositives showed increased levels of serum B2M. Thus, quantitative analysis
      of B2M may be useful as an early nonspecific marker of HIV infection and immune
      dysfunction. The prognostic value of B2M was assessed in a follow up study of 54
      HIV seropositives in a 2 yr period. Within this period, B2M levels were found to
      be significantly increased in these subjects (1.2 mg/1 to 4.6 mg/1, P less than
      0.001). Three of the subjects who showed high increase in the B2M levels,
      progressed to AIDS-related condition, whereas one progressed to persistent
      generalised lymphadenopathy. Thus, the rising levels of B2M appears to correlate
      well with disease progression.

PMID- 1398803
TI  - HIV infection in patients of liver cirrhosis.
AB  - A total of 130 patients of liver cirrhosis (97 males, 33 females; aged 9-70 yr)
      of various etiologies were subjected to anti HIV antibodies testing by ELISA and
      supplementary Western Blot (WB) tests. Eleven patients were positive by ELISA. Of
      these 11 patients, 5 were WB positive, 4 were WB negative and 2 were
      indeterminate. Of the 5 WB positive patients none had received blood transfusions
      and one was a homosexual. These results indicate that HIV infection was present
      in 3.8 per cent patients of liver cirrhosis. Further studies are required on a
      large number of patients to recommend HIV testing routinely in cirrhotic
      patients.

PMID- 1398804
TI  - Polymerase chain reaction based diagnostic assay for identification of hepatitis
      B virus.
AB  - A highly sensitive polymerase chain reaction (PCR)-based diagnostic assay was
      developed to detect the presence of hepatitis B virus (HBV) in human serum. The
      assay involved amplification of HBV DNA sequences using primers specific to HBV.
      This in vitro enzymatic amplification technique, when used in combination with
      molecular hybridization assay can detect HBV genome in the patient's serum, with
      a higher degree of sensitivity than achieved with dot blot assay. The assay can
      identify samples containing 3-10 virus particles.

PMID- 1398805
TI  - Occurrence of multi-drug resistant Salmonella typhi in Calcutta.
AB  - Blood and faecal samples were collected from 122 hospitalised patients of
      Calcutta clinically suspected to have enteric fever, for isolation of S. typhi.
      It was isolated from 34.4, 4.9 and 4.1 per cent patients by blood culture, stool
      culture and by both respectively. The in vitro drug susceptibility testing showed
      that all the isolates were resistant to chloramphenicol, ampicillin and
      trimethoprim-sulphamethoxazole, but were uniformly susceptible to ciprofloxacin,
      norfloxacin and furazolidone. In view of the appearance of multi-drug resistant
      S. typhi in Calcutta, great care should be exercised in the use of newer
      quinolone derivatives.

PMID- 1398806
TI  - Comparison of selective media for optimal recovery of Clostridium difficile from
      diarrhoeal stools.
AB  - Five selective media were compared for their efficacy in the recovery of C.
      difficile from stool specimens. Of 341 diarrhoeic stool samples, 38 (11%) yielded
      C. difficile. Eighty per cent of the isolates were detected on modified
      taurocholate cycloserine cefoxitin fructose agar (MTCCFA) and 73 per cent were
      detected on taurocholate cycloserine cefoxitin fructose agar (TCCFA). MTCCFA was
      also found superior to the other four media as it supported better growth of C.
      difficile colonies, by effectively suppressing the competing microflora. These
      results suggest that the recovery rate of C. difficile could be enhanced when
      routine media, incorporated with taurocholate and lower concentration of
      cycloserine and cefoxitin, is used for the isolation of C. difficile from
      diarrhoeic stool.

PMID- 1398807
TI  - Mannose-resistant haemagglutination by Campylobacter jejuni--a preliminary
      communication.
AB  - Ten strains of C. jejuni each isolated respectively from patients with diarrhoea
      and from chicken intestine (10 strains from each source) were examined for
      presumptive colonization factor(s) by measuring their cell surface hydrophobicity
      and haemagglutination. None of the strains expressed cell surface hydrophobicity.
      However, 14 strains (7 from either source) showed variable haemagglutination
      pattern with human, sheep and rabbit erythrocytes in the presence of 0.5 per cent
      D-mannose. Thus, mannose resistant haemagglutinin(s) may be involved in the
      colonization of intestinal mucosal surfaces by C. jejuni.

PMID- 1398808
TI  - Multiply resistant Haemophilus influenzae type b causing meningitis.
AB  - The isolation from patients of meningitis, of two multidrug resistant strains of
      H. influenzae is of relevance to the empirical treatment of meningitis patients.
      The isolates produced beta lactamase and had higher MICs as compared to the four
      H. influenzae strains sensitive to the drugs commonly used for the treatment of
      meningitis. The cephalosporins and gentamicin were found to be effective
      antibiotic agents. The occurrence of resistance to ampicillin, chloramphenicol,
      cloxacillin, cotrimoxazole, tetracycline, penicillin and erythromycin is of
      concern.

PMID- 1398809
TI  - Kinetics of specific IgM in patients of hepatic amoebiasis.
AB  - Entamoeba histolytica (EH) specific IgM was measured in 54 patients with
      diagnosed amoebic liver abscess (ALA), 13 with non-suppurative hepatic amoebiasis
      (NSHA) and 50 controls. The mean levels of EH specific IgM, estimated by ELISA
      were significantly raised in patients of invasive amoebiasis (both ALA and NSHA)
      compared to controls (P less than 0.05). EH specific IgG was also raised in both
      groups of patients. Follow up of patients with ALA showed a significant decline
      (P less than 0.05) in the specific IgM levels three months after treatment while
      the specific IgG antibodies persisted in high titres (1:160). Only four patients
      of NSHA could be followed up and all showed a decline in specific IgM levels.
      Raised specific serum IgM seems to be an indicator of active (invasive)
      amoebiasis.

PMID- 1398810
TI  - Mosquito repellent activity of oils from Vitex negundo Linn. leaves.
AB  - Oil obtained from stream distillate of V. negundo leaves was fractionated by
      column chromatography. Mosquito repellence activity, as evaluated against Aedes
      aegypti was mainly confined to the most polar fractions. The protection period
      against mosquito bites by polar fractions ranged between 1-3 h. However, the mean
      protection period values of these fractions did not show significant increase in
      the subsequent subfractions.

PMID- 1398811
TI  - Laboratory assessment of indigenous plant extracts for anti-juvenile hormone
      activity in Culex quinquefasciatus.
AB  - Of 15 plants tested, five plant extracts showed anti-juvenile hormone-like
      activity against laboratory colonised late fourth instar larvae and adult female
      mosquitoes. Petroleum ether extract of Eichhornia crassipes and acetone extracts
      of Ageratum conyzoides, Cleome icosandra, Tagetes erectes and Tridax procumbens
      showed growth inhibitory (P less than 0.001) and juvenile hormone mimicing
      activity to the treated larvae of C. quinquefasciatus.. Larval pupal
      intermediates, demalanised pupae, defective egg rafts and adult with deformed
      flight muscles were few noticeable changes. Biting behaviour was observed to be
      affected only in Ageratum, Cleome and Tridax extracts (P less than 0.001). Loss
      of fecundity was observed in the treated mosquitoes but no sterilant effects
      could be seen. Adults, obtained from larvae exposed to the plant extracts
      produced significantly shorter egg-rafts (P less than 0.005) than in control.

PMID- 1398812
TI  - Seasonal abundance, natural survival & resting behaviour of Phlebotomus papatasi
      (Diptera: Phlebotomidae) in Pondicherry.
AB  - A study was carried out on the seasonal abundance, natural survival and resting
      behaviour of Ph. papatasi in four ecologically different areas of Pondicherry.
      The average indoor resting density ranged from 2.25 (May 1989) to 16.70/man hour
      (October 1989). Ph. papatasi was observed to be predominantly endophilic in its
      resting behaviour. A significant positive correlation was observed between
      rainfall and relative density. The daily survival of adult population ranged from
      0.893 to 0.949 and showed significant positive correlation with relative
      humidity. Examination of the abdomen of indoor resting females showed that the
      entire period of gonotrophic cycle was spent indoors.

PMID- 1398813
TI  - Non-oliguric acute renal failure in gout.
AB  - Four patients of pure gouty nephropathy are presented. Gout was of over five
      years duration and asymptomatic nephropathy manifested as non-oliguric acute
      renal failure. Diseases commonly associated with it like uric acid stones,
      urinary tract infections, hypertension, diabetes mellitus, hyperlipidemid,
      obesity and nephrosclerosis were absent. Reduction in serum uric acid level
      resulted in prompt improvement in renal functions. Early detection and control of
      hyperuricemia may help in restoration of renal functions.

PMID- 1398814
TI  - A retrospective study on scorpion sting in a pediatric age group in a hospital in
      Calcutta.
AB  - During 1985-1989, in Calcutta Medical College Hospitals, of 152 children of 1-6
      year age group admitted with the history of scorpion sting 18 (11.8%) died.
      Maximum numbers of stings were inflicted in the fingers. Important clinical
      features recorded were circulatory failure, breathlessness, profuse sweating,
      vomiting, local oedema and convulsion. Incidences of scorpion stings were much
      more frequent in the summer and rainy seasons than in the winter season.

PMID- 1398815
TI  - Bilateral anterior fracture dislocation shoulder--two case reports.

PMID- 1398816
TI  - Genetic red cell defects and malaria.

PMID- 1398817
TI  - A new Branemark single tooth abutment: handling and early clinical experiences.
AB  - A new prosthetic concept, today available under the name CeraOne, for single
      tooth replacement with the Branemark system is described. This concept is
      characterized by a new design of the prefabricated components. A mechanical
      torque driver is used together with a gold screw and a special counter-torque
      device to ensure that the screw is tightened in an optimal manner to resist screw
      loosening and only transmit minor stress to the fixture interface. Another
      characteristic is the use of a prefabricated cap of sintered aluminum oxide as
      the basis for the ceramic crown. The crown is cemented to provide better esthetic
      possibilities even in situations of somewhat unfavorable fixture placement.

PMID- 1398818
TI  - Management of an anterior defect with a removable partial denture supported by
      implants and residual teeth: a case report.
AB  - The treatment of a patient with a major defect in the anterior region of the
      mandible is described. A large part of the anterior dental arch and underlying
      mandibular bone was involved in the defect. A removable partial denture supported
      by implants as well as residual teeth was used to restore the defect. Compared
      with a traditional removable partial denture, which was used by the patient for
      several years as an interim prosthesis, the application of implants resulted in
      improved functional comfort and stability.

PMID- 1398819
TI  - Titanium implants in irradiated tissue: benefits from hyperbaric oxygen.
AB  - Since the introduction of osseointegrated titanium implants for bone-anchored
      facial and dental prostheses, an increasing number of irradiated patients are
      being treated with this technique. Although the number of patients who have had
      titanium implants after irradiation is limited, available statistics point to a
      tendency of a higher implant loss frequency as compared with nonirradiated
      patients. This review discusses factors behind deleterious tissue effects and
      implant failures from irradiation and points to possibilities to improve the
      surgical outcome with special reference to hyperbaric oxygen therapy.

PMID- 1398820
TI  - Theoretical analysis of the fatigue life of fixture screws in osseointegrated
      dental implants.
AB  - Metal fatigue failure of the gold screw used to retain a fixed prosthesis to
      Branemark osseointegrated fixtures/abutments has been analyzed theoretically.
      Mechanical engineering principles show the importance of appropriate preload
      being applied through the gold screw to the gold cylinder and abutment. The
      significance of the screw design and necessity of applying the correct torque to
      achieve a long fatigue life for the screw are also described. The consequence of
      misalignment of a gold cylinder to an abutment is discussed.

PMID- 1398821
TI  - Implant superstructures: a comparison of ultimate failure force.
AB  - Because of reported prosthodontic failures, alternative implant abutments and
      screws with suggested strength superiority have been manufactured. However,
      little quantitative data are available to support these claims. This study
      compared the force necessary to cause failure in many of the more commonly used
      implant and abutment combinations. An 18-mm cantilever test prosthesis was
      constructed for each system and loaded on an MTS machine until failure occurred
      (n = 5 for each sample). The mean failure forces ranged from 1.22 to 17.23 kg.
      The failure force and location of failure for each individual system are
      reported.

PMID- 1398823
TI  - Fixture placement posterior to the mental foramen with transpositioning of the
      inferior alveolar nerve.
AB  - The results of 10 fixture placement operations with transpositioning of the
      inferior alveolar nerve are presented. Nerve transpositioning increased the
      operating time, but with experience this time should be reduced. Neurosensory
      dysfunction of the inferior alveolar nerve was found in 7 of 10 operated sites 1
      week after surgery. Six months postoperatively, altered sensation was still
      present in 2 patients. Nerve function was normal in all patients 1 year
      postoperatively. The stability of fixtures was satisfactory throughout the
      examination period and the procedure should prove useful in treatment of the
      resorbed mandible posterior to the mental foramina.

PMID- 1398822
TI  - Failures and complications in 127 consecutively placed fixed partial prostheses
      supported by Branemark implants: from prosthetic treatment to first annual
      checkup.
AB  - Ninety-six partially edentulous maxillae and mandibles were consecutively treated
      with 127 freestanding fixed prostheses supported by 354 implants. The patients
      were followed for 1 year and the overall success rate was 98.6% for the examined
      implants. None of the inserted prostheses was lost during the observation period.
      The most commonly reported problems during the first year of function were
      related to loose gold screws and esthetic complaints, complications that were
      easily resolved. Furthermore, the total number of complications was low and was
      less than has been reported for routine full-arch fixed prostheses.

PMID- 1398824
TI  - Patient satisfaction with overdentures supported by one-stage TPS implants.
AB  - Sixty-four edentulous patients with severe conventional denture problems who had
      been treated with 218 one-stage titanium plasma sprayed (TPS) screw implants and
      new overdentures were clinically evaluated and questioned on their experiences
      with treatment up to 6 years after implant insertion. The results demonstrated
      that only seven of the implants had failed during this period, resulting in a
      success rate of 97%. Most of the patients (95%) were satisfied with their new
      overdentures, and almost all patients (98%) found that their new dentures fit
      comfortably. Only 3% of the patients treated would not recommend that others
      undergo similar treatment.

PMID- 1398825
TI  - Prosthesis fabrication using electrical discharge machining.
AB  - Fixed-removable implant prostheses provide solutions for some of the problems
      associated with implant dentistry, especially in the maxilla. The technique for
      using electrical discharge machining to create a precise passive fit between the
      substructure bar and the removable suprastructure is presented. The advantages,
      disadvantages, and complications associated with this type of prosthesis are
      discussed.

PMID- 1398826
TI  - A morphometric and biomechanic comparison of titanium implants inserted in rabbit
      cortical and cancellous bone.
AB  - The removal torques for screw-shaped pure titanium implants inserted in rabbit
      tibia and the femoral part of the knee joint and the tissue response to these
      implants, as quantitated with light microscopic morphometry on ground sections,
      were compared after 6 weeks, 3 months, and 6 months. The bone surrounding the
      femoral intra-articular implants was mostly cancellous, while cortical bone was
      formed around the tibial implants. The torque needed to remove the intra
      articular implants increased with time, but there was no such increase for the
      tibial implants. At 6 weeks, significantly less torque was needed to remove the
      intra-articular implants in spite of the fact that significantly more bone was
      found in the threads of these implants as compared with the tibial implants. When
      calculating the amount of bone in threads situated in the cortical and
      subchondral passage, more was found in the threads of the tibial implants, which
      corresponded to the higher removal torque. Additional light microscopic
      observations on implants unscrewed after 12 months in rabbit tibia indicated that
      rupture occurred between the implant surface and calcified bone. Findings
      indicate that the resistance to unscrewing is dependent on the amount of compact
      bone surrounding a titanium implant.

PMID- 1398827
TI  - Osteogenesis of hydroxyapatite and tricalcium phosphate used as a bone
      substitute.
AB  - Hydroxyapatite (HA) and tricalcium phosphate (TCP) are useful for grafting and
      augmentation of bone tissue. In this study, conventional and histochemical
      transmission electron microscopy were used to study osteogenic events at the
      interface between the implanted materials and adjacent tissue from 1 to 4 weeks
      postoperatively. The microscopic results indicated that TCP was resorbed more
      rapidly than HA after implantation, with a notable breakdown of material and
      replacement by mesenchymal cells with ultrastructural features resembling
      osteoprogenitor cells and collagen up to 4 weeks postoperatively. Alkaline
      phosphatase and acid phosphatase reactivity in the tissues helped to identify and
      differentiate the histologic differences observed between HA and TCP.

PMID- 1398828
TI  - A new self-tapping Branemark implant: clinical and radiographic evaluation.
AB  - A new self-tapping Branemark implant designed for denser bone qualities was
      evaluated with regard to insertion technique, complications, marginal bone
      remodeling, and survival rate. Thirty patients, representing 21 mandibles and 9
      maxillae, participated in the study. In each patient both standard and self
      tapping implants were placed, and a total of 179 implants, 88 self-tapping and 91
      standard, were inserted. Thirteen of 62 mandibular self-tapping implants reached
      their correct positions only after using the screw tap or the cylinder wrench for
      manual insertion. No such problems were noted when using standard fixtures after
      bone pre-tapping. In the maxillae, neither of the two implant designs presented
      any problems. One standard and one self-tapping fixture failed to osseointegrate.
      Radiolucencies were seen in the bone around the apical portion of two fixtures,
      one of each design. The mean marginal bone resorption after 1 year of follow-up
      was 0.5 to 0.6 mm for the two fixture types.

PMID- 1398829
TI  - Reconstructing the atrophic mandible with inferior border grafting and implants:
      a preliminary report.
AB  - Advanced mandibular atrophy is a serious surgical reconstruction challenge.
      Previous experience with an inferior border approach has been favorable.
      Predictably successful osseointegrated implants ultimately allow loading of the
      healed grafts. The technique described uses a freeze-dried, gamma-irradiated
      cadaver mandible packed with autogenous iliac crest bone. An extraoral approach
      allows augmentation without disrupting use of an intraoral prosthesis during
      healing. The incidence of infection and resorption can be reduced. Fewer problems
      with neurosensory disturbances common with some of the superior border, or
      sandwich osteotomy, grafting techniques were experienced. The use of implants to
      ultimately load the bone should result in less resorption than in those
      techniques using a conventional removable prosthesis.

PMID- 1398830
TI  - Comparative surface microanalysis of failed Branemark implants.
AB  - The chemical composition and topography of an implant surface determine the human
      immunologic system response. This study compared the surfaces of 13 Branemark
      oral implants, 11 that came from retrieved specimens which failed initially or
      did not osseointegrate and 2 that were never implanted (controls). The period of
      implantation in human jaws varied between 3 and 20 months. After cleaning and
      sterilization, the topography, surface chemical composition, and thickness of the
      oxide layer were studied. The results obtained with scanning electron microscopy
      did not show any significant topographic differences among the specimens. X-ray
      spectrographic microanalysis showed very similar composition (titanium and
      amounts less than 0.5% of other elements) in the outermost layer of the analyzed
      specimens. The Auger spectroscope revealed considerable percentage differences in
      the amount of carbon and silicon in the last monolayers, which could be
      attributed to handling or to an inadequate cleaning process. This places the
      retrieved specimens out of the acceptable statistical limits of contamination by
      introducing a factor of doubt for long-term prognosis in the hypothetical
      situation of their re-use.

PMID- 1398831
TI  - Visualization and initial characterization of the titanium boundary of the bone
      implant interface of osseointegrated implants.
AB  - A simple procedure has allowed consistent visualization of the titanium boundary
      of the bone-implant interface of osseointegrated titanium implants at the
      electron microscope level. This was accomplished by embedding the intact bone
      implant specimen block with low-viscosity resin prior to removal of the device in
      preparation for sectioning. The titanium boundary consisted of either a thin,
      compact amorphous electron dense layer, a broad layer of dense amorphous
      granules, or both. This material was removed by decalcification in formic acid
      (prior to embedding) and did not diffract electrons (ie, was noncrystalline).
      Scanning-transmission electron microscopy-EDX analysis indicated the presence of
      titanium, calcium, and phosphorus in the electron dense material. Field emission
      scanning electron microscopy-EDX dot-mapping analysis confirmed the presence of
      these elements and mapped them to the same locations at the implant-interface
      boundary.

PMID- 1398832
TI  - Failures and complications in 92 consecutively inserted overdentures supported by
      Branemark implants in severely resorbed edentulous maxillae: a study from
      prosthetic treatment to first annual check-up.
AB  - Overdentures were consecutively inserted in 92 severely resorbed maxillae and
      followed for 1 year. The dentures were supported by a total of 430 implants. Of
      these, 69 (16%) became loose and were removed during the follow-up period. The
      mobile implants caused 7 complete failures of the overdenture treatment.
      Postinsertion maintenance was more extensive for the overdentures than for fixed
      prostheses supported by implants. Problems arose in relation to the mucosa around
      the implants, and there were also fatigue fractures of the acrylic resin and the
      retentive clips. Fewer speech problems were reported in the overdenture group
      when compared to those with fixed prostheses.

PMID- 1398833
TI  - Surface analysis of an original Branemark implant and three related clones.
AB  - Selected surface characteristics of screw-type titanium dental implants from four
      different manufacturers were evaluated. Considerable differences in surface and
      near-surface contaminants were demonstrated. The fixture treated with
      radiofrequency glow discharge (plasma) demonstrated the thinnest titanium oxide
      layer and the cleanest surface.

PMID- 1398834
TI  - Mandibular ridge augmentation with simultaneous onlay iliac bone graft and
      endosseous implants: a preliminary report.
AB  - Mandibular onlay composite grafts (autogenous iliac bone and titanium cylindrical
      threaded endosseous dental implants) were placed in seven patients with advanced
      bone resorption. All seven patients have experienced uncomplicated healing and
      continuous, uninterrupted prosthesis use without soft tissue or mechanical
      complications for 1 to 4 years. This preliminary report includes a discussion of
      the indications for the procedure, potential alternative management of the
      severely resorbed mandible, and details of the surgical procedure illustrated by
      two patients who received this treatment modality.

PMID- 1398835
TI  - Three-dimensional force measurements on mandibular implants supporting
      overdentures.
AB  - The purpose of this study was to determine masticatory and functional forces in
      three axes on mandibular implants supporting overdentures. Five edentulous test
      subjects were selected, each having two mandibular implants. Three-dimensional
      piezoelectric force transducers were mounted on the two-part ITI Bonefit implants
      and rigidly connected to the denture. Forces in vertical, lateromedial, and
      anteroposterior directions were measured by means of electrostatic plotter
      records. The test modalities were light tapping, grinding, maximal occlusal
      force, and chewing test food. Results showed that the five subjects developed
      similar stress patterns but quantitatively different occlusal and chewing forces.
      In all but one subject, reduced maximal occlusal force was found compared to
      dentate subjects and edentulous subjects with fixed partial prostheses supported
      by implants. The recordings of chewing cycles when eating test food resulted in
      very regular rhythmic strokes, similar to those of dentate subjects but with
      slightly reduced speed. All stress patterns showed that occlusal and chewing
      forces were mainly directed in vertical, medial, and anterior dimensions. The
      dominating component was vertical.

PMID- 1398836
TI  - A retrospective evaluation of endosseous titanium implants in the partially
      edentulous patient.
AB  - Partial edentulism in 34 patients was consecutively treated using the Branemark
      osseointegration technique. A total of 102 implants was tested for mobility,
      signs and symptoms of infection, and radiographic bone levels. All patients had
      at least a 6-month follow-up of prosthesis function (mean 22.5 months). An
      overall success rate of 88.2% was observed. Twenty-five of 28 maxillary implants
      and 65 of 74 mandibular implants were successfully placed and restored. Twelve
      failures were observed; 7 were not integrated at the time of stage 2 surgery
      while 5 occurred after prosthetic reconstruction. The results of this study
      suggest that the Branemark osseointegration procedure can be used to treat
      partially edentulous patients with a high degree of success.

PMID- 1398837
TI  - Nasofacial prostheses supported by osseointegrated implants.
AB  - Surgical ablation in the nasofacial area may lead to defects that can be treated
      with maxillofacial prosthetic restorations retained by osseointegrated implants.
      When the prosthesis is large or impacted by masticatory or orbicularis muscle
      forces, the use of implants placed in available facial skeleton bone may be
      desirable. Available sites for implant placement in the facial skeleton are
      described, and a craniofacial site classification is suggested. Two examples of
      patients treated for nasofacial defects are presented.

PMID- 1398838
TI  - Heat distribution in bone during preparation of implant sites: heat analysis by
      real-time thermography.
AB  - The purpose of this experiment was to observe and measure the distribution of
      heat to bones and the maximum temperature that developed when cutting bone with
      drills. Generation of heat that spread in the presence or absence of irrigation
      when drilling with IMZ, Branemark, and ITI implant (F type) drills was observed
      in the pig rib via thermography. Without irrigation, the condition of heat spread
      in each drill and bur differed according to bur shape and drilling site. Maximum
      heat temperature without irrigation was higher than that with irrigation for any
      IMZ, ITI, and Branemark drill.

PMID- 1398839
TI  - Clinical parameters of evaluation during implant maintenance.
AB  - This paper reviews investigations concerning the clinical parameters of
      evaluating dental implants during the maintenance phase of therapy. Clinical
      parameters that are discussed include mobility, gingival alterations, tissue
      movement, probing and attachment level measurements, bleeding upon probing,
      occlusion, and microbial monitoring. The role of implant radiology is discussed
      and encompasses radiographic interpretation, interval, and technique.

PMID- 1398840
TI  - Public awareness and acceptance of dental implants.
AB  - To investigate public awareness and acceptance of dental implants, 120 adult US
      citizens were asked to answer a questionnaire. Of the 109 persons who completed
      the questionnaire, 77% had heard about dental implants, mostly through media and
      lay persons. Only 17% named a dentist or physician as the source of information.
      Persons with many missing teeth were not more aware of implants than those with
      fewer missing teeth. Of 19 removable denture prosthesis wearers, 15 knew about
      implants but only one third learned of them from their dentist or physician. Of
      84 persons with information about implants, 51 would consider implant treatment,
      17 would not, and 16 were undecided. Esthetics was the most frequent motivating
      factor favoring implants, while high cost was the most frequent argument against
      them. Younger interviewees were significantly more often in favor of implants
      than older persons. It was concluded that public awareness and acceptance of
      dental implants are high. Dentists and physicians, however, play only a minor
      role as sources of information.

PMID- 1398841
TI  - Bone regeneration around titanium dental implants in dehisced defect sites: a
      clinical study.
AB  - Insufficient bone volume can be a significant problem when placing dental
      implants. This clinical study was designed to evaluate bone regeneration
      potential at dehisced dental implant sites. Nineteen titanium dental implants
      with exposed threads were studied. To create a secluded space for bone formation,
      an expanded polytetrafluoroethylene (e-PTFE) membrane was placed over the exposed
      implant sites secured with an implant cover screw and completely covered with the
      flap. Three membranes perforated the overlying soft tissue during the healing
      time and were removed prematurely. The remaining membranes were removed after an
      uneventful healing period of 4.5 to 6 months. Fourteen of 19 dehisced implant
      sites were completely covered with newly formed bonelike tissue; 4 implants
      demonstrated partial bone fill at reentry and 1 implant showed partial fill with
      soft tissue. In five implant sites a reentry was performed between 6 and 9 weeks;
      nonmineralized fibrous tissue was found to fill the space under the membrane. At
      16 of the 19 implant sites there were similar dehiscence-type defects that were
      evaluated as a group. These dehiscences varied from 2.0 to 9.0 mm. The percentage
      of bone fill at reentry ranged from 28.4% to 100% (mean 89.6%; SD 22.51; SE 5.63)
      and was highly significant (P < .0001). Six to 12 months after prosthesis
      connection, 12 of the 19 implants were available for radiographic interpretation
      and an average bone loss of 1.73 mm (SD = 0.43) was measured. This surgical
      application of an e-PTFE membrane suggested a viable clinical method for
      enhancing bone formation around dental implants.

PMID- 1398842
TI  - Presurgical tomographic assessment for dental implants. 1. A modified imaging
      technique.
AB  - A modified technique for presurgical evaluation of intraosseous implant placement
      using linear tomography has been developed. The simplified technique is
      applicable to tomographic systems equipped with a cephalometric head positioner
      (cephalostat) and a fiberoptic positioning light system. It provides precise
      cross-sectional images for the assessment of bone morphology and associated
      anatomic structures. This technique is more comfortable for patients who are
      unable to tolerate the positioning of submentovertex projections used to estimate
      horizontal angulation of the head position and to determine the depth of
      radiographic cut. Instead, the positioning light and casts are used to make these
      two determinations.

PMID- 1398843
TI  - Implant and prosthetic treatment of the edentulous maxilla using a bar-supported
      prosthesis.
AB  - Functional and anatomical considerations led to a new concept of an implant
      supported bar prosthesis in the edentulous maxilla. The cantilever situation is
      avoided by the placement of endosseous cylindrical implants (type IMZ) in the
      maxillary tuberosities distal to the maxillary sinus. Full arch support is
      provided by the symmetrical insertion of six IMZ implants in the tuberosity,
      canine, and incisor regions. After 4 months of healing, a milled precision bar
      and removable prosthesis are fabricated and supported by the implants.

PMID- 1398844
TI  - Osseointegrated Branemark implants used to retreat a fractured mandibular bone
      plate staple implant: a case report.
AB  - This article describes postimplant follow-up and retreatment of a 66-year-old
      patient with an esthetically compromising fixed maxillary tissue-integrated
      prosthesis and a mobile mandibular overdenture stabilized by precision
      attachments with a gold clip bar cemented to the transmucosal posts of a bone
      plate staple implant. Following successful completion of prosthodontic treatment,
      the patient returned with a fracture of the left transmucosal pin in the
      mandibular bone plate staple implant that was retreated with Branemark implants
      and a fixed prosthesis.

PMID- 1398845
TI  - Developmental progress of infants in the early years.

PMID- 1398846
TI  - Assessment of cerebral palsy.

PMID- 1398847
TI  - Changing the delivery of speech therapy.
AB  - The paper seeks to describe the way in which changes were brought about in the
      delivery of speech therapy to children in special schools. Changes were necessary
      in order to make most use of existing staff resources and to investigate the
      effects of treatment. Both aims were achieved, but improvements to practice are
      continuing. A change in service organisation across the two state services of
      Health and Education takes time to bring about.

PMID- 1398848
TI  - Infant feeding practices among patients of pediatricians and general
      practitioners.
AB  - In an attempt to document the infant feeding practices among patients of
      pediatricians and general practitioners, a study was carried over a period of one
      month and data of 10,374 infants were recorded using a pre-printed proforma
      marked by a simple 'tick' for each patient. The results showed: (i) initiation of
      breastfeeding was delayed in nearly half of the cases beyond 24 hours; (ii)
      introduction of bottle feeding in more than half of infants by the age of 4
      months and (iii) introduction of solid foods later than eight months in almost
      half of infants. While breastfeeding is practised by 78% of women, only one in
      five practice exclusive breastfeeding till 4-6 months, and very few avoid bottle
      feeds. Much education and change in behaviour is needed if optimal benefit of
      breastfeeding in India is to be realised.

PMID- 1398849
TI  - Determination of bone width in malnourished children under 5, and its inter
      relationship with mid arm muscle thickness, subcutaneous fat thickness and the
      mid upper arm girth.
AB  - The mid upper arm of 516 malnourished children (one to five years) were studied
      radiographically for changes in bone width, muscle mass and subcutaneous fat, of
      malnutrition at different ages. The data was studied by statistical analysis,
      determining the correlation coefficients of each of the factors. The findings
      indicate that previous assumptions about the components and the changes of the
      mid upper arm girth (MUG) in chronic severe malnutrition, were perhaps too
      simplistic.

PMID- 1398850
TI  - Iron nutritional status of preschool children.
AB  - Low hemoglobin and low MCHC levels were indicative of high incidence of iron
      deficiency in preschool children. The extent of iron deficiency as assessed by
      serum ferritin and free erythrocyte protoporphyrin showed a different trend.
      While FEP levels were highly suggestive of extensive iron deficiency (in 40-45%
      of children below the age of 5 years), low serum ferritin was seen in only 16-20%
      of children. The discrepant finding of high serum ferritin, and high erythrocyte
      protoporphyrin despite low MCHC in the present study, possibly reflects iron
      deficiency status along with chronic infection resulting in hyperferritinemia and
      hyperprotoporphyrinemia. It may be also due to associated folate deficiency
      resulting in non utilization of iron leading to the elevated levels of
      protoporphyrin.

PMID- 1398851
TI  - Chloramphenicol clearance in typhoid fever: implications for therapy.
AB  - We prospectively studied the pharmacokinetics of intravenous Chloramphenicol
      succinate (CS) in children (age 6 months-14 years) with culture proven typhoid
      fever (n = 30) and non typhoidal illnesses (n = 10). CS was administered in three
      different dosage regimens (50, 75 and 100 mg/kg/d-q 6 hourly). Liver function
      tests were monitored. Plasma trough and peak chloramphenicol concentrations were
      measured by HPLC analysis after 42 hrs. The 50 mg/kg/day dosage schedule was
      terminated midway through the study, as blood levels were consistently low and
      two patients with typhoid relapsed, children with typhoid had significantly lower
      clearance of CS in comparison with those with non-typhoidal illness (0.29 +/- 0.1
      versus 0.5 +/- 0.37 1/kg/hr, P 0.05). There was no significant difference between
      mean peak and trough concentrations of chloramphenicol on 100 mg/kg/day and 75
      mg/kg/day in children with typhoid. However, two children on 100 mg/kg/day dosage
      developed trough concentrations greater than 20 mcg/ml. No correlation was found
      between CS clearance and serum bilirubin, SGPT (alanine transaminase) and
      alkaline phosphatase. Our data show altered clearance of CS in children with
      typhoid and suggests that 75 mg/kg/day may be a safer dose in children with
      hepatic dysfunction in typhoid.

PMID- 1398852
TI  - Multidrug resistant Salmonella typhi in Delhi.
AB  - In 1990, we isolated 158 strains of Salmonella typhi from blood cultures of
      patients suffering from typhoid fever. Seventy nine (50%) of these isolates were
      found to be simultaneously resistant to chloramphenicol, ampicillin and
      cotrimoxazole. These strains were also resistant to streptomycin and
      tetracycline, but sensitive to gentamicin, amikacin and cephalexin. The minimum
      inhibitory concentrations of chloramphenicol and trimethoprim for a
      representative number of these strains were found to be greater than 1024
      micrograms/ml and greater than 128 micrograms/ml respectively. Majority of the
      multidrug resistant (MDR) strains tested against cefotaxime (23/23),
      ciprofloxacin (38/38) and amoxycillin plus clavulanic acid (23/24) were sensitive
      to these drugs.

PMID- 1398854
TI  - Attitude of children towards medication and health in urban and rural schools of
      Tamil Nadu.
AB  - In most cases of Pediatric practice, medicine is prescribed to the child without
      taking into consideration his likes and dislikes. The medicines are usually
      thrust upon them. Though our foremost aim is to cure the patient, we should give
      due importance to make the process of cure as comfortable as possible. Keeping
      this in mind, opinion poll of around nine hundred school students from rural and
      urban population of age ranging from 11 years to 16 years was taken. The result
      is analysed and suggestion is given to rationalise the treatment for better
      compliance.

PMID- 1398853
TI  - Circulating immune complexes in leukaemias and lymphomas.
AB  - Circulating immune complexes (ClC) were estimated in 78 patients of leukaemias
      and lymphomas by Clq deviation ELISA and PEG assay. In all leukaemias a
      significant elevation in ClC was seen at the time of first presentation. While in
      ALL a decrease occurred on therapy as partial or complete remission was achieved,
      no such fall was seen in AML or CML-BC when treated. ClC levels were much higher
      in non-Hodgkins lymphoma than in Hodgkins disease and showed a direct correlation
      with B symptoms and activity of the disease. The ClC levels were highest in null
      ALL followed by those in common ALL and T-ALL. The mean duration of remission in
      patients of ALL without elevation in ClC was much longer than in those with ClC.

PMID- 1398855
TI  - Hemostatic profile in neonatal septicemia.
AB  - Hemostatic profile was studied in 25 full term non-asphyxiated neonates with
      blood culture-proven septicemia. Observations were compared with that of 25
      healthy, non-asphyxiated, full term, birth weight and age-matched controls.
      Detailed coagulation tests & platelet studies were done in each of the 50
      neonates by standard techniques. Hemostatic defects occurred in 96% of the
      septicemic neonates and none in the control group irrespective of the occurrence
      of clinical bleeding. The coagulation tests were deranged in 805 and platelet
      function tests in 92% of patients. These tests were significantly deranged in
      septicemic neonates as compared to control group.

PMID- 1398856
TI  - Participatory health communication and action through women groups in rural
      areas.
AB  - Twelve women groups in 10 villages of block Beri were identified and activized
      through participatory health communication actions for mother and child
      development. Women could undertaken responsibilities on key health problems
      concerning mothers and children. In these villages over 58% of antenatal mothers
      now used home made clean packets for delivery and chose right place for delivery.
      Most of them (60%) now initiate breast feeding immediately after delivery as
      against 23% in the year 1988. Over 54% of women now drink chlorinated water and
      almost same proportion used sugar salt solution in diarrheal diseases. Thus women
      have become self reliant in chlorination of wells and pots as also in diarrheal
      diseases management. Practice of hand washing has been almost universalized.

PMID- 1398857
TI  - Prevalence and abuse of psychoactive substances in children and adolescents.
AB  - The present study has been carried out in the slum areas of Gorakhpur city,
      covering a population of 10,187 in the four colleges of Gorakhpur. Five hundred
      and eighty children and adolescents in urban slums, and 750 college students
      between 10-18 years were studied by means of a questionnaire card for detection
      of prevalence rate and various others co-relates of abuse of psychoactive
      substances. Overall, prevalence of abuse of psychoactive substances was 25% in
      slum areas, and 18% in college students. Abuse of tobacco was most frequent
      (50.3% & 72.5%) followed by that of alcohol (11.7% & 16.2%) in both the groups
      respectively. Cannabis was also used by some children (0.6%). More abusers were
      from Hindu families with low educational status and low family income.
      Surprisingly no one was found to be abusing tablets and street drugs.

PMID- 1398858
TI  - Successful management of Bland--White-Garland syndrome in infancy.

PMID- 1398859
TI  - Action plan for revamping the family welfare programme in India.

PMID- 1398860
TI  - Early contact and the bonding phenomenon.

PMID- 1398861
TI  - Epidemiological co-relates of low birth weight in rural Tamil Nadu.
AB  - A total of 328 consecutive births born between July and September 1990 were
      analysed. The rate of LBW was 24.6%. The mean birth weight was 2.72 kg (+/- 0.44
      kg). Association between LBW and parity, mother's age, mother's height,
      gestational weight, risk status at pregnancy and antenatal care was observed.
      These results indicate that there is a need to strengthen maternal services to
      address the problem of LBW in India.

PMID- 1398862
TI  - Failure to isolate verotoxin producing Escherichia coli from patients of
      haemolytic uremic syndrome.
AB  - Haemolytic Uremic Syndrome (HUS) been defined as the simultaneous occurrence of
      acute renal failure in children with haemolytic anemia and thrombocytopenia. This
      clinical condition that has been recognized is an important cause of acute renal
      failure in children.

PMID- 1398863
TI  - Citrobacter sepsis in infants.
AB  - A study of blood cultures from 320 cases of neonatal sepsis showed 136 (42.5%) to
      be positive for bacterial growth; of these 82 (60.29%) isolates being gram
      negative bacilli. Citrobacter was the commonest gram negative bacilli isolated.
      Other commonly isolated gram negative organisms were Pseudomonas, Klebsiella,
      Salmonella typhimurium, Acinetobacter and Escherichia coli. Antibiotics
      susceptibility pattern revealed the isolates to be resistant to commonly used
      antibiotics.

PMID- 1398864
TI  - Oral rehydration therapy in severely malnourished children with diarrheal
      dehydration.
AB  - Fifty patients of grade III & IV malnutrition with diarrhoeal dehydration were
      rehydrated using the WHO recommended ORS. Serum sodium and potassium levels were
      estimated at admission and 24 hours later. Forty seven patients were successfully
      rehydrated orally. In 7 patients the level of dehydration at initial assessment
      was overestimated. Periorbital edema developed in 25.5% of the patients
      rehydrated. No patient had cardiac failure or convulsions during therapy. Though
      persistent hyponatremia and hypokalemia were found in 10.6% and 19.15% cases
      respectively after rehydration, the incidence decreased as compared to the pre
      hydration levels and was comparable to that found in malnourished children
      without diarrhea who served as controls in the present study. Oral rehydration
      was discontinued in three patients due to development of excessive vomiting in
      one case and paralytic ileus in two. Thus WHO ORS can be used safely in children
      with severe malnutrition but constant monitoring is required.

PMID- 1398865
TI  - Epidemiological evaluation of oral polio vaccine efficacy in Delhi.
AB  - Forty seven cases of poliomyelitis and 94 controls were studied for immunization
      status. Unmatched analysis with one control per case and two controls per case
      was done to find out the ratio of the odds of immunization in diseased
      individuals as compared with the nondiseased (odds ratio). This ratio (OR) was
      used further to calculate oral polio vaccine efficacy. OPV efficacy was found to
      be 93% with 95% confidence limits of 75-98%.

PMID- 1398866
TI  - Influence of maternal nutritional status on mode of delivery and asphyxia
      neonatorum.
AB  - To assess the influence of maternal malnutrition on the mode of delivery and
      asphyxia neonatorum, a cross sectional survey of 615 women in the age group of 20
      28 yrs at the time of delivery was done. Women with chronic ailments and
      complicated pregnancies were excluded. The mothers were then classified into
      three groups based on Weight Height Product Index (WHPI) namely well nourished
      (WN), moderately malnourished (MMN) and severely malnourished (SMN). The
      proportion of asphyxiated babies among the three groups did not differ (P greater
      than 0.05). Abnormal deliveries like caesarean section were more common among SMN
      group compared to WN group ((P less than 0.01). No such difference was made out
      between MMN and WN groups (P greater than 0.05).

PMID- 1398867
TI  - Effect of G-6 PD deficiency on sickle cell disease in Saudi Arabia.
AB  - High incidence of G6PD deficiency has been reported in areas of the eastern
      province of Saudi Arabia where sickle cell gene is also prevalent. This study was
      conducted to assess the co-incidence of this enzymopathy with Hb S and its
      influence upon the clinical and hematological expression of sickle cell disease.
      Eighty three children with SS disease, 145 patients with sickle cell trait and
      100 random cord blood as samples with normal Hb AF, and an FS electrophoretic
      pattern respectively were examined. The frequency of interaction of G6PD
      deficiency with Hb S was found significantly increased but no effect of this
      enzyme defect was discerned on the clinical and hematological status of
      homozygous sickle cell disease.

PMID- 1398868
TI  - Perinatal risk factors in neonatal infections.
AB  - Perinatal risk factors were studied among 50 cases of neonatal septicemia and 200
      matched normal neonates during one year period. The consanguinity among parents,
      birth order and sex of the baby did not increase the risk for developing
      septicemia. There was significant increase in the risk for septicemia when the
      duration of labour was more than 24 hours (P less than 0.01), time interval
      between rupture of membrane and delivery of baby was more than 12 hours (P less
      than 0.001), liquor was meconium stained or foul smelling (P less than 0.001) and
      delivery was operative (P less than 0.01). The neonatal factors identified with
      risk for septicemia were preterm delivery (P less than 0.01), low birth weight (P
      less than 0.01), birth asphyxia (P less than 0.001) assisted ventilation (P less
      than 0.001) and intravenous alimentation (P less than 0.02). Identification of
      high risk pregnancies and appropriate management can minimize many of the above
      risk factors which in turn will reduce the occurrence of neonatal sepsis.

PMID- 1398869
TI  - Otitis media of childhood.

PMID- 1398871
TI  - Nasal polyposis in children.

PMID- 1398870
TI  - Foreign body in ear and upper aerodigestive tract.

PMID- 1398872
TI  - Auditory brainstem evoked responses in infants and children.

PMID- 1398873
TI  - Rehabilitation of a deaf child.

PMID- 1398874
TI  - The tricho-rhino-phalangeal syndromes I and II.

PMID- 1398875
TI  - Primary non-Hodgkins lymphoma of the rectum.

PMID- 1398876
TI  - Association of antral, jejuno-ileal atresias and biliary peritonitis--an unusual
      case.

PMID- 1398877
TI  - L-thyroxine therapy for congenital hypothyroidism and Marfan syndrome.

PMID- 1398878
TI  - Bladder diverticulum causing acute urinary retention.

PMID- 1398879
TI  - Association of Giardia lamblia with Vibrio in cholera cases.

PMID- 1398880
TI  - Syrinomelia bipus (mermaid) with meningocele.

PMID- 1398881
TI  - Contrasting excitatory and inhibitory effects of adenosine in blood pressure
      regulation.
AB  - Administration of adenosine results in profound hypotension without the expected
      activation of reflex sympathetic and renin mechanisms in most animal models. This
      action can be explained by the vasodilatory and neuroinhibitory effects of
      adenosine. It is generally considered an inhibitory neuromodulator because it
      inhibits the release of virtually all neurotransmitters studied and produces
      hyperpolarization of neurons. In contrast, adenosine produces vasoconstriction of
      some vascular beds, including the renal and pulmonary circulations. Renal
      vasoconstriction is caused by activation of A1 receptors and involves an
      interaction with angiotensin II. In other vascular beds adenosine releases
      eicosanoids, including thromboxane, also resulting in vasoconstriction. Adenosine
      induced vasoconstriction is transient and species dependent. Neither the receptor
      type, the molecular mechanisms of these actions, nor their significance to
      pathophysiological processes have been defined. Adenosine also has an apparent
      excitatory effect in the nucleus tractus solitarii. Microinjections of adenosine
      into this brain stem nucleus lead to decreased sympathetic tone and hypotension
      similar to those produced by the excitatory amino acid glutamate. The mechanism
      that explains this action has recently been explored and involves the release of
      glutamate by adenosine. Adenosine also stimulates afferent fibers mediating
      sympathetic activity, including renal and myocardial afferent nerves, and carotid
      and aortic chemoreceptors. Afferent nerve activation seems to be more pronounced
      in humans and may explain most of the cardiovascular and respiratory actions of
      adenosine in this species. Finally, animal studies suggest that endogenous
      adenosine plays a role in the regulation of the baroreceptor reflex and restrains
      the full expression of renin-dependent hypertension.

PMID- 1398882
TI  - Trandolapril inhibits atherosclerosis in the Watanabe heritable hyperlipidemic
      rabbit.
AB  - The effects of trandolapril (0.25 mg/kg body wt per 48 hours) on aortic
      atherosclerosis were examined in the Watanabe heritable hyperlipidemic rabbit
      treated from 3 to 12 months of age. Trandolapril caused a significant decrease in
      atherosclerotic involvement of the intimal surface of total aorta from 56.3 +/-
      5.0% in control Watanabe rabbits to 35.0 +/- 4.1% with treatment (p less than
      0.01). The largest reductions were observed in descending thoracic aorta where
      21.8 +/- 5.7% of intimal surface was involved in the trandolapril-treated animals
      versus 54.4 +/- 7.7% in the control group (p less than 0.01). Significant
      decreases also occurred in ascending aorta/arch and abdominal aortic segments.
      Cholesterol content of descending thoracic aorta was also significantly reduced
      in the trandolapril-treated rabbits. The atherosclerotic plaques in aorta from
      trandolapril-treated rabbits appeared to contain less foam cells and relatively
      greater amounts of connective tissue than those from control animals. These
      studies indicate that trandolapril inhibits aortic atherosclerosis in the
      Watanabe heritable hyperlipidemic rabbit. The similarity in results between the
      current study and that using captopril suggests that the antiatherosclerotic
      action of trandolapril and captopril represents a class effect related to
      angiotensin converting enzyme inhibition.

PMID- 1398883
TI  - Renin expression in renal ablation.
AB  - To determine whether expression of the renin-angiotensin system (RAS) is
      influenced by the degree of renal ablation, male Sprague-Dawley rats underwent
      uninephrectomy, 1 1/3 nephrectomy, or sham operation. Renin and angiotensinogen
      messenger RNA (mRNA) were not different among the three groups 2 weeks after
      surgery. The time course of expression of renin mRNA after 1 1/3 nephrectomy
      showed no difference versus controls at 2 and 4 weeks and a decrease at 6 weeks
      after surgical ablation. Because nephrons adjacent to the infarcted area in the 1
      1/3 nephrectomy may be hypoperfused and a source of increased renin synthesis,
      intrarenal distribution of tissue renin content, renin mRNA, and immunostainable
      renin were examined in separate groups of rats subjected to 1 1/3 nephrectomy.
      The kidney was divided into two pieces, one containing the scar and scar-adjacent
      tissue and the other portion the tissue distant from the scar. Tissue renin
      content, renin mRNA, and immunostainable renin were significantly greater in the
      scar-adjacent tissue compared with the nonscar tissue. Immunoreactive renin was
      seen in the juxtaglomerular apparatuses as well as in vascular elements proximal
      to the juxtaglomerular apparatus and within mesangial cells of some glomeruli of
      the scar-adjacent tissue. In conclusion, immunostainable renin, tissue renin
      content, and renin mRNA were increased in scar-adjacent tissue after 1 1/3
      nephrectomy. We speculate that this unique scar-associated redistribution of
      renin may play a pathophysiological role in the progression of renal disease.

PMID- 1398884
TI  - Collagen deposition and the reversal of coronary reserve in cardiac hypertrophy.
AB  - The aim of this study was to clarify how collagen deposition or medial
      hypertrophy of the vascular wall affects the coronary dilator reserve in pressure
      overloaded hearts and whether inhibition of collagen deposition reverses the
      abnormalities after relief of pressure overload. We used ascending aortic banding
      and debanding methods and superimposed beta-aminopropionitrile in some of the
      banded rats (50 mg/kg i.p., twice a day). Ten weeks of banding increased in vivo
      peak systolic left ventricular pressure and produced medial hypertrophy, an
      increase in collagen deposition in the myocardial and perivascular tissues, and
      myocardial hypertrophy in the banded group without beta-aminopropionitrile
      treatment. Superimposition of beta-aminopropionitrile treatment on banding
      inhibited the increase in collagen deposition. In the groups debanded after the
      10-week banding period, both with and without beta-amino-propionitrile treatment,
      medial and myocardial hypertrophy regressed 4 weeks after debanding. We estimated
      coronary dilator reserve in Langendorff preparations perfused with modified
      Tyrode's solution containing oxygenated bovine red blood cells and serum albumin.
      The ratio of reactive peak flow after brief ischemia-to-resting flow decreased in
      both of the banded groups. After debanding, the ratio remained lower in the
      banded group without beta-aminopropionitrile treatment than in the control group.
      However, debanding in the group with beta-aminopropionitrile treatment increased
      the ratio to a level similar to that of the control group. Thus, in pressure
      overloaded cardiac hypertrophy with coronary hypertension, coronary reserve seems
      to be determined by medial hypertrophy independently of collagen deposition, but
      collagen deposition plays an important role in the reversal of vasodilator
      reserve after relief of the overload.

PMID- 1398885
TI  - Cerebral glucose utilization and blood flow in adult spontaneously hypertensive
      rats.
AB  - Not only blood pressure but also behavioral activity, brain morphology, and
      cerebral ventricular size differ between young spontaneously hypertensive rats
      (SHR) and normotensive Wistar-Kyoto (WKY) rats. This suggests that cerebral blood
      flow and cerebral metabolism may vary between these two rat strains. To test this
      hypothesis, we measured local cerebral glucose utilization in 31 brain areas of
      26-30-week-old rats. Local cerebral blood flow was also assessed in these same
      areas. Cerebral glucose utilization was measured by the 2-deoxyglucose method;
      cerebral blood flow was determined by the iodoantipyrene method. In virtually all
      gray matter structures, the apparent rate of glucose utilization was lower in SHR
      than in normotensive WKY rats; the interstrain differences varied significantly
      among structures and were statistically significant (uncorrected t tests) in 14
      of 28 gray matter areas. Local cerebral blood flow was fairly similar in the two
      rat strains. The coupling of blood flow to glucose utilization varied
      significantly among brain areas in normotensive WKY rats as well as in SHR. In a
      number of gray matter structures, the coupling of flow to metabolism differed
      between hypertensive and normotensive animals. These data suggest that for many
      brain areas, either glucose utilization or glucose partitioning differs between
      WKY rats and SHR.

PMID- 1398886
TI  - Effects of L-arginine on forearm vessels and responses to acetylcholine.
AB  - This study was designed to investigate the effects of L-arginine (the substrate
      of endothelium-derived nitric oxide) in human forearm vessels. We examined
      whether intra-arterial infusion of L-arginine dilated forearm vessels and
      augmented vasodilatory responses to acetylcholine in young, healthy humans. The
      left brachial artery was cannulated for drug infusions and direct measurement of
      arterial pressure. Forearm blood flow was measured by a strain gauge
      plethysmograph. Intra-arterial infusions of L-arginine at 10, 20, 40, and 60
      mg/min increased forearm blood flow from 4.7 +/- 0.6 to 4.9 +/- 0.5, 5.7 +/- 0.5,
      7.2 +/- 0.8, and 8.2 +/- 0.9 ml.min-1.100 ml-1, respectively (n = 8, p less than
      0.01), whereas D-arginine at the same doses did not alter forearm blood flow (n =
      7). Intra-arterial infusions of acetylcholine (n = 7) (4, 8, 16, and 24
      micrograms/min) and sodium nitroprusside (n = 5) (0.2, 0.4, 0.8, and 1.2
      micrograms/min) increased forearm blood flow dose dependently (p less than 0.01
      for both). Arterial pressure was not altered with infusions of these drugs.
      Responses to acetylcholine were augmented with simultaneous intra-arterial
      infusion of L-arginine at 10 mg/ml (p less than 0.01) but not with D-arginine.
      Responses to sodium nitroprusside were not altered by L-arginine. These results
      in human forearm resistance vessels support the notion that vasodilation induced
      by acetylcholine is a result of the conversion from L-arginine to endothelium
      derived nitric oxide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398887
TI  - Phosphoramidon-sensitive effects of big endothelins in the perfused rabbit
      kidney.
AB  - The enzymatic conversion of human big endothelins (1, 2, and 3) to their
      respective active metabolites (endothelin-1, -2, and -3) was investigated in the
      perfused rabbit kidney through the pressor- and eicosanoid-releasing properties
      of these peptides. Intra-arterial bolus injections of endothelin-1 and -2 (5-50
      pmol), endothelin-3 (100-250 pmol), and big endothelin-1 and -2 (100-250 pmol)
      into the kidney produced dose-dependent increases of perfusion pressure, whereas
      big endothelin-3 was inactive at doses up to 1,000 pmol. Endothelin-1 and -2 (10
      nM), endothelin-3 (100 nM), and big endothelin-1 and -2 (100 nM) are potent
      enhancers of prostacyclin release without inducing any release of thromboxane B2
      in the perfused kidney. In contrast, big endothelin-3 did not trigger the release
      of eicosanoids. A metalloprotease inhibitor, phosphoramidon (100 microM, 60
      minutes), reduced the prostanoid release and pressor responses induced by big
      endothelin-1 and -2 without affecting the response induced by endothelin-1, -2,
      and -3. These results suggest the presence of a phosphoramidon-sensitive
      endothelin converting enzyme that converts the precursors of endothelin-1 and -2,
      but not of endothelin-3, in the renal vasculature of the rabbit.

PMID- 1398888
TI  - Impaired renal vascular reactivity in prehypertensive Dahl salt-sensitive rats.
AB  - We have previously shown that renal vascular resistance is less in Dahl salt
      sensitive rats than salt-resistant rats fed 1% NaCl diets; however, renal
      vascular resistance increases before nonrenal vascular resistance as salt
      sensitive rats develop hypertension when fed 8% NaCl diets. When salt-resistant
      rats are given 8% NaCl diets, renal vascular resistance decreases. The current
      study reports effects of atrial natriuretic peptide, nitroprusside,
      norepinephrine, angiotensin II, and endothelin-1 on renal and nonrenal vascular
      resistance in prehypertensive salt-sensitive and salt-resistant rats given 1%
      NaCl diets; doses used did not affect blood pressure. Resistance of nonrenal
      vessels in salt-sensitive and salt-resistant rats responded similarly to dilators
      or constrictors. However, atrial natriuretic peptide and nitroprusside decreased
      renal vascular resistance of salt-resistant rats (by 65%, p less than 0.01) but
      not that of salt-sensitive rats. Norepinephrine, angiotensin II, and endothelin-1
      increased renal vascular resistance in salt-sensitive rats by 126%, 135%, and
      135%, respectively (p less than 0.01); norepinephrine and angiotensin II did not
      change renal vascular resistance of salt-resistant rats, but endothelin-1
      decreased renal vascular resistance in salt-resistant rats by 30% (p less than
      0.01). Reactivity of nonrenal blood vessels in prehypertensive salt-sensitive and
      salt-resistant rats was similar when infused with dilators or constrictors in
      doses used. By contrast, renal vessels of salt-sensitive rats did not dilate in
      response to atrial natriuretic peptide and nitroprusside but were hypersensitive
      to norepinephrine and angiotensin II. Endothelin-1 caused renal vasoconstriction
      in salt-sensitive rats and renal vasodilation in salt-resistant rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1398889
TI  - Cardiovascular and plasma catecholamine responses to exercise in blacks and
      whites.
AB  - The purpose of the present study was to assess possible racial differences in
      cardiovascular and plasma catecholamine responses to dynamic exercise. A biracial
      group of normotensive college-age men (15 blacks, 15 whites) were tested for
      maximal oxygen uptake, resting blood pressure, and heart rate. Subjects then rode
      a cycle ergometer at 25%, 50%, and 75% of peak oxygen uptake (6 minutes at each
      stage). Blood pressure and heart rate were measured during supine rest, seated
      rest, and at each stage of exercise with an automated blood pressure monitor. At
      each stage, venous blood was sampled to allow determination of plasma
      norepinephrine and epinephrine, and cardiac output was measured with the carbon
      dioxide rebreathing technique. The results indicated that resting blood pressure
      was similar for blacks and whites (114/68 versus 115/68 mm Hg, respectively).
      Blacks exhibited greater systolic and diastolic blood pressures during submaximal
      dynamic exercise. However, blacks also showed a trend toward a positive parental
      history of hypertension, which has been associated with an increased pressor
      response. Racial differences did not exist for heart rate or cardiac output, but
      blacks had higher values for total peripheral resistance both at rest and during
      exercise. Although no overall racial differences were seen for plasma
      catecholamine concentrations at rest, blacks had significantly lower levels of
      norepinephrine (1,275 versus 1,556 pg/ml) and higher levels of epinephrine (306
      versus 216 pg/ml) than whites at the highest work rate. The current study
      confirms the increased pressor response to exercise in normotensive blacks.
      Blacks had an elevation in total peripheral resistance that was not accompanied
      by an increase in plasma norepinephrine levels.

PMID- 1398890
TI  - Variability between current definitions of 'normal' ambulatory blood pressure.
      Implications in the assessment of white coat hypertension.
AB  - The assessment of white coat hypertension is complicated by the lack of generally
      agreed-on normal limits of ambulatory blood pressure. To assess the influence of
      four of these limits on the prevalence of white coat hypertension and the
      corresponding distribution of left ventricular hypertrophy, we performed 24-hour
      ambulatory blood pressure monitoring and echocardiographic studies in 346
      untreated patients with essential hypertension and 47 age-matched normotensive
      control subjects. The upper limits of normal daytime ambulatory blood pressure
      were lower using standards drawn from clinically normotensive populations than
      using standards drawn, partly or entirely, from general populations. The
      prevalence of white coat hypertension differed markedly using the different
      standards, being 12.1%, 16.5%, 28.9%, and 53.2% (chi 2 = 346.0, p less than
      0.0001). Left ventricular mass index averaged 77 g/m2 in the control group, 85
      g/m2 in the two groups with white coat hypertension defined by using standards
      drawn from normotensive populations (both comparisons not significant versus
      control group), and 90 and 98 g/m2 in the two groups with white coat hypertension
      defined by using the other two standards (both p less than 0.01 versus control
      group). The prevalence of echocardiographic left ventricular hypertrophy was 0%
      in the control group, 2.4% and 3.5% in the two groups with white coat
      hypertension defined by using standards drawn from normotensive populations, and
      9.0% and 14.7% in the other two groups with white coat hypertension (p less than
      0.05 and p less than 0.01, respectively, versus control group).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1398891
TI  - Increased waist/hip ratio, metabolic disturbances, and family history of
      hypertension.
AB  - To test whether nonhypertensive subjects with a two-generation positive family
      history of hypertension (PFH) are characterized by disturbed glucose metabolism,
      16 men (38 +/- 6 years old) with PFH and 25 subjects matched for age and with
      negative family histories of hypertension (NFH) were recruited. Blood pressure;
      serum lipids; erythrocyte transmembrane sodium transport; and the glucose, plasma
      insulin, and C-peptide responses to an oral glucose tolerance test were
      investigated. Subjects with PFH had higher blood pressure, body weight, body mass
      index (BMI), waist/hip ratio (WHR), and abdominal sagittal diameter than subjects
      with NFH. Baseline blood glucose, plasma insulin, serum lipids, and transmembrane
      sodium transport did not differ between the two groups. Blood glucose levels at
      90 and 120 minutes after oral glucose were significantly higher in subjects with
      PFH than in controls. Blood glucose adjusted for BMI and WHR at 90 minutes was
      significantly related to a PFH. Plasma insulin level at 90 minutes during the
      glucose load was significantly higher in subjects with PFH. In multivariate
      analysis, WHR was significantly related to baseline blood pressure, insulin, and
      cholesterol, whereas BMI was significantly associated with the insulin response
      to the oral glucose tolerance test. Transmembrane sodium transport was
      significantly related to blood pressure only. In conclusion, subjects with PFH
      are characterized by increased body weight and BMI, increased visceral fat
      accumulation, and an altered blood glucose response to an oral glucose load. It
      was also shown that WHR was related to blood pressure and that BMI was more
      related to cholesterol and response to glucose loading than a PFH was.

PMID- 1398892
TI  - Regulation of vasopressin receptors in deoxycorticosterone acetate-salt
      hypertension.
AB  - Since arginine vasopressin may play a role in mineralocorticoid hypertension, we
      examined the effects of deoxycorticosterone acetate (DOCA)-salt on vasopressin V1
      and V2 receptor binding and their second messengers, inositol phosphate and
      adenylate cyclase, respectively, in liver and kidney to determine whether altered
      vasopressin receptor binding is pathogenetic in mineralocorticoid hypertension.
      The mean arterial blood pressure of mineralocorticoid (DOCA-salt)-treated rats
      (163 +/- 1 mm Hg) was increased compared with control salt-treated rats (salt)
      (122 +/- 1 mm Hg) and water-treated rats (120 +/- 1 mm Hg; p less than 0.001).
      Mineralocorticoid treatment also increased plasma sodium, osmolality, and
      vasopressin concentration (p less than 0.001). In the hypertensive animals, there
      was a reduction in hepatic V1 (DOCA-salt, 91 +/- 12; salt, 132 +/- 13; and water,
      145 +/- 13 fmol/mg protein; p less than 0.05) and renal V2 receptor binding
      density (DOCA-salt, 53 +/- 5; salt, 93 +/- 9; and water, 95 +/- 9 fmol/mg
      protein; p less than 0.01), although receptor affinities remained unaltered. In
      contrast, the density of renal V1 receptors was increased by mineralocorticoid
      treatment (DOCA-salt, 24 +/- 2; salt, 16 +/- 2; water, 18 +/- 1 fmol/mg protein;
      p less than 0.05), although the affinity was unchanged. Downregulation of V2
      receptors was associated with a decrease in maximum cyclic adenosine
      monophosphate levels (DOCA-salt, 19 +/- 4; salt, 49 +/- 6; water, 53 +/- 9
      pmol.mg protein-1.10 min-1; p less than 0.05), whereas changes in V1 receptor
      levels were not associated with changes in maximum inositol phosphate
      levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1398893
TI  - Association of red blood cell sodium leak with blood pressure in recombinant
      inbred strains.
AB  - Red blood cell Na+ content as well as ouabain-resistant Na+ and Rb+ (K+)
      transport (susceptible or resistant to inhibition by loop diuretics) were
      determined in spontaneously hypertensive rats (SHR) and normotensive Brown Norway
      (BN) rats the erythrocytes of which were incubated in either saline or Mg(2+)
      sucrose medium. Elevated ouabain-resistant Na+ net uptake contrasted with
      slightly decreased red blood cell Na+ content in SHR compared with BN rats.
      Acceleration of furosemide- and bumetanide-sensitive Na+ fluxes contributed to
      enhanced ouabain-resistant Na+ influx into SHR erythrocytes in saline medium,
      whereas higher furosemide- or bumetanide-resistant Na+ efflux caused greater
      ouabain-resistant Na+ efflux in Mg(2+)-sucrose medium. Furosemide- and bumetanide
      resistant Rb+ leaks were augmented in SHR erythrocytes. The association of the
      disclosed ion transport alterations with blood pressure was examined in 20
      recombinant inbred strains derived from F2 SHR x BN hybrids. Ouabain-resistant
      Na+ uptake as well as furosemide- and bumetanide-resistant Na+ inward leaks (but
      not red blood cell Na+ content or furosemide- and bumetanide-sensitive Na+ net
      uptake) cosegregated with systolic and pulse pressures but not diastolic pressure
      of the recombinant inbred strains. In contrast, neither ouabain-resistant Na+
      efflux nor any component of ouabain-resistant Rb+ uptake correlated positively
      with blood pressure of the recombinant inbred strains. Increased ouabain
      resistant Na+ influx was compensated for by accelerated ouabain-sensitive Na+
      extrusion because red blood cell Na+ content was not elevated in the hypertensive
      strains. Thus, high cell Na+ turnover rates might be related to genetic
      hypertension if an altered Na+ inward leak would be less effectively compensated
      for in tissues involved in cardiovascular regulation.

PMID- 1398894
TI  - Epinephrine and the genesis of hypertension.

PMID- 1398895
TI  - Oligodendrocytes and myelin formation along the optic tract of the developing
      hamster: an immunohistochemical study using the Rip antibody.
AB  - The monoclonal antibody Rip recognizes an antigen specific to oligodendrocytes
      and their processes (Friedman et al: Glia 2:380, 1989). We have used this
      antibody to document the appearance of oligodendrocytes and the sequence of
      ensheathment of axons along the optic tract (OT) and within its major target
      areas in neonatal (P3-P21) and adult hamsters. Myelination of axons in the visual
      pathway follows an overall proximo-distal gradient. On P3, immunopositive, pre
      ensheathing oligodendrocytes are detected in the OT ventral to the lateral
      geniculate body (LGB) whereas myelin segments are present around OT axons by P5.
      The first pre-ensheathing oligodendrocytes are detected medially in the LGB on P7
      and myelinated axons in the overlying OT by P11. In the superior colliculus, pre
      ensheathing oligodendrocytes are present in the optic fiber layer (SO) on P7, but
      not in the superficial gray layer (SGS) until P11. Myelination of axons within SO
      proceeds along a marked rostro-caudal gradient. On P14, axons in rostral SO are
      heavily myelinated; thereafter, ensheathment continues caudally within the SO and
      the SGS. The progressive invasion of oligodendrocytes along the proximo-distal
      axis of the optic pathway, and the corresponding myelination of OT axons, are
      discussed in the context of a possible inhibitory role of oligodendrocytes in
      regulating the regenerative propensity of retinotectal axons.

PMID- 1398896
TI  - Immuno-electron microscopical localization of vimentin and glial fibrillary
      acidic protein in mouse astrocytes and their precursor cells in culture.
AB  - Immuno-electron microscopy was used to localize the distribution of vimentin and
      glial fibrillary acidic protein (GFAP) in mouse astrocytes and their precursor
      cells in primary cultures. In astroblasts and astrocytes, vimentin and GFAP form
      intermediate filaments (IF), which are heteropolymers, as previously observed in
      gliomas. Astrocytes and their precursor cells may have IF composed of GFAP
      vimentin heteropolymer or vimentin alone, but IF composed of GFAP only were not
      seen. It seems that the formation of IF that are GFAP-vimentin heteropolymers is
      a feature of normal astroglia development and that the ratio of GFAP to vimentin
      in these IF reflects the degree of differentiation and functional state of the
      cell.

PMID- 1398897
TI  - Serotonin uptake by astrocytes in situ.
AB  - Co-localization of glial fibrillary acidic protein (GFAP) and radioactivity was
      examined after intraventricular injection of [3H]5-HT in adult rat brains.
      Radioactivity localized over GFAP-positive astrocytes was seen, especially when
      image-enhancing techniques were applied to the data. Also slices prepared from
      astrogliotic hippocampi of rats pretreated with kainic acid showed a twofold
      increased uptake of [3H]5-HT compared to control slices. This indicates that the
      uptake of [3H]5-HT seen in primary astrocyte cultures also occurs for astrocytes
      in situ. Also, as with astrocyte cultures, only some of the GFAP(+) astrocytes in
      situ showed localization of radioactivity, supporting the concept of
      intraregional heterogeneity of astrocyte functions.

PMID- 1398898
TI  - Glial response to dorsal root lesion in the irradiated spinal cord.
AB  - Exposure of the rat lumbar spinal cord to X-rays during the early postnatal
      period results in a marked reduction in the glial populations within the
      irradiated region. The present study was undertaken to determine what effects
      this reduction of glia, particularly astrocytes, has on the pattern and
      characteristics of the scar formation that follows root injury in the normal
      spinal cord. Morphological assessments 60 days following injury of the right L4
      dorsal root revealed a distinct difference in the extent of the astrocyte
      response between the irradiated and the nonirradiated rats. In the nonirradiated
      animals, a thick astrocytic scar composed of multiple layers of astrocyte
      processes formed over the dorsal horn and adjacent portions of the dorsal surface
      of the cord. This astrocytic response was not confined to the surface of the
      spinal cord but extended also into the root, i.e., into regions normally
      considered as PNS. In irradiated rats, the astrocytes did not form a thick scar
      nor did they extend into the injured root. Instead, they formed a glia limitans
      and were at most only one or two layers thick over the region of cord comparable
      to that occupied by the thick astrocytic scar in the nonirradiated rats.
      Mechanisms involved in the glial response of the irradiated spinal cord to dorsal
      root injury are discussed, particularly with regard to the possible positive
      effect that this reduction in scar formation may have on regrowth of injured
      dorsal root axons into the spinal cord environment.

PMID- 1398899
TI  - The practical effects of health care reform.

PMID- 1398900
TI  - Let states take the lead.

PMID- 1398901
TI  - Current issues in profiling quality of care.
AB  - Profiling provider performance for the assessment of quality involves a number of
      issues related to selection of appropriate quality measures, subsequent data
      collection and analysis, and selection of standards of comparison. This article
      emphasizes the limitations of current data systems for this purpose and discusses
      hierarchical modeling as the optimal analytic approach for analyzing resulting
      data. Mention is made of the difficulties of achieving large enough sample sizes
      for statistical significance at the individual provider level. Finally, the
      article discusses feasible options for profiling quality.

PMID- 1398902
TI  - Physician-based measures of Medicare access.
AB  - Physician payment reforms implemented in January 1992 have dramatically changed
      the way payments for services are determined under the Medicare Part B program.
      This paper presents new measures of access using physician-level data that
      provide a baseline for monitoring changes in access that might occur as these
      payment reforms unfold and that allow us to examine recent access trends. Our
      results suggest that Medicare beneficiaries as a group currently have a high
      degree of access to care, and that access generally improved between 1986 and
      1990.

PMID- 1398903
TI  - Rural and urban hospital closures, 1985-1988: operating and environmental
      characteristics that affect risk.
AB  - Due to congressional concern that rural hospitals were particularly disadvantaged
      by Medicare's Prospective Payment System, the U.S. General Accounting Office
      investigated the role of Medicare and other factors in hospitals' risk of
      closure. This paper reports on the findings of that study, which compared the
      risk of closure among urban and rural hospitals during 1985 to 1988, the period
      after implementation of PPS. When hospital operating and environmental
      characteristics were held constant, the odds of closure in rural and urban areas
      differed significantly only for private nonprofit hospitals. Although a number of
      factors were associated with hospitals' higher risk of closure, we did not find
      evidence that Medicare was a major factor associated with financial distress or
      closure during the 1985 to 1988 period.

PMID- 1398904
TI  - Zidovudine's impact on resource use by patients with symptomatic HIV illness: a
      large sample analysis.
AB  - This study used a longitudinal data set of 4,957 patients and 39,455 patient
      months of observation, drawn from 17 months of data on patients with symptomatic
      HIV disease identified from the New York State Medicaid Program. Multivariate
      regression analysis was used to evaluate the effect of AZT on the use of several
      medical services. The results show that AZT produced substantial reductions in
      resource use. Patients who took AZT were hospitalized fewer days per month and,
      including the cost of the drug, had Medicaid expenditures that were several
      hundred dollars lower per month. The reduction in total expenditures is largely
      accounted for by a reduction in inpatient expenditures and an increase in
      pharmacy expenditures. These effects were temporary, however, as the impact of
      the drug decreased with each month of use. There were no declines in expenditures
      and utilization after approximately 7 to 9 months of AZT use.

PMID- 1398905
TI  - The process and outcome of hospital care for Medicaid versus privately insured
      hospital patients.
AB  - Some have argued that low Medicaid payment rates compromise the accessibility and
      quality of medical care for Medicaid beneficiaries. In this study we compare the
      process and outcome of hospital care for Medicaid versus privately insured
      hospital patients. We studied 4,033 emergency patients admitted with a principal
      diagnosis of acute myocardial infarction, to Massachusetts hospitals in 1987.
      After we statistically adjusted for differences among patients relating to
      clinical and demographic characteristics and the type of hospital where treatment
      occurred, we found that the Medicaid patients had longer hospital stays but were
      less likely to receive three selected coronary procedures. Moreover, after
      controlling for confounding variables, we found the risk of death for Medicaid
      patients to be almost twice as high as for privately insured patients.

PMID- 1398906
TI  - Improving organ donation: compensation versus markets.
AB  - Proposals suggesting monetary compensation of organ donors to increase donation
      rates for transplantation are founded on the ethical premise that the principal
      criterion for organ procurement policy should be patients' health and not the
      personal preferences and philosophies of policymakers. In this paper, we argue
      that a market-based organ procurement system is superior to both the current
      altruistic-based system and a system based on compensation without a market. A
      market system would address both the problem of potential donors refusing to
      donate and that of their never being asked, whereas the altruistic system
      addresses neither problem and a system of compensation addresses only the former.
      Empirical evidence suggests that the latter (not being asked) is the predominant
      cause of the current shortage of organs. Our discussion shows that collection
      rates are likely to be substantially higher under a market system.

PMID- 1398907
TI  - Enteropathogenic Escherichia coli.

PMID- 1398908
TI  - Mucin degradation in the human colon: production of sialidase, sialate O
      acetylesterase, N-acetylneuraminate lyase, arylesterase, and glycosulfatase
      activities by strains of fecal bacteria.
AB  - Oligosaccharide side chains of human colonic mucins contain O-acetylated sialic
      acids and glycosulfate esters. Although these substituents are considered to
      protect the chains against degradation by bacterial glycosidases, sialate O
      acetylesterase, N-acetylneuraminate lyase, and glycosulfatase activities have
      been found in fecal extracts. To better define the source of these activities, we
      measured extracellular and cell-bound sialidase, sialate O-acetylesterase, N
      acetylneuraminate lyase, arylesterase, and glycosulfatase activities produced by
      23 isolates of human fecal bacteria grown anaerobically in a hog gastric mucin
      culture medium; these represented dominant populations of fecal anaerobes,
      facultative anaerobes, and the subset of mucin oligosaccharide-degrading
      bacteria. Every strain produced sialidase and high levels of arylesterase, and
      all but five facultative anaerobes produced sialate O-acetylesterase. Sialic
      acids containing 2 mol or more of O-acetyl ester per mol of sialic acid were
      cleaved from mucin glycoproteins more slowly by sialidases of mucin
      oligosaccharide-degrading stains than were sialic acids containing 1 or 0 mol,
      and only N-acetyl- and mono-O-acetylated sialic acids were recovered from enzyme
      digests of a mucin containing di-O-acetylated sialic acids. No detectable N
      acetylneuraminate lyase activity was produced by any strain, but low activity was
      induced by increasing the glycoprotein-bound sialic acid concentration in the
      culture medium of six Escherichia coli strains. Using lactitol-6-sulfate as a
      substrate, we found weak glycosulfatase activity in the partially purified,
      concentrated enzyme mixture in the culture supernatants of four mucin
      oligosaccharide-degrading strains but in none of the unconcentrated culture
      fractions. We conclude that the presence of two or more O-acetyl groups on sialic
      acids inhibits enteric bacterial sialidases but that production of sialate O
      acetylesterases by several populations of enteric bacteria lessens the likelihood
      that mucin oligosaccharide chains terminating in O-acetylated sialic acids are
      protected from degradation. Sialate O-acetylesterases have a role in bacterial
      degradation of mucin glycoproteins in the human colon.

PMID- 1398909
TI  - Effects of alginase on the natural history and antibiotic therapy of experimental
      endocarditis caused by mucoid Pseudomonas aeruginosa.
AB  - The exopolysaccharide (alginate) of mucoid strains of Pseudomonas aeruginosa is
      believed to be an important virulence factor. The ability of an alginate
      deploymerizing enzyme (alginase) to modify the polymorphonuclear leukocyte (PMN)
      directed and antibiotic-mediated phagocytosis and killing of mucoid P. aeruginosa
      was studied both in vitro and in vivo. In vitro, pretreatment of a mucoid P.
      aeruginosa strain (144MR) resulted in a significant enhancement of PMN
      phagocytosis and killing of the organism (P less than 0.05), to levels similar to
      that observed with its nonmucoid mate, strain 144NM. Moreover, alginase treatment
      of the mucoid strain 144MR caused a substantial removal of bacterial cell surface
      alginate as assessed by immunofluorescence staining with a murine monoclonal
      antialginate antibody. The experimental endocarditis model was used to evaluate
      the in vivo effect of alginase in modifying the course of a deep-seated
      pseudomonal infection caused by mucoid strain 144MR. In right-sided endocarditis,
      in which PMNs normally mediate spontaneous clearance of the organism from cardiac
      vegetations (A. S. Bayer, J. Yih, C. Y. Chiu, and C. C. Nast, Chemotherapy 35:278
      288, 1989), the presence of the alginate exopolysaccharide on strain 144MR was
      associated with an inability to reduce intravegetation pseudomonal counts over a
      13-day postinfection period; in contrast, right-sided vegetations infected with
      the nonmucoid strain 144NM underwent significant reductions in bacterial
      densities over this same time (P less than 0.05). Administration of alginase
      intravenously (i.v.) (750 enzyme units per day for 7 days) to animals with right
      sided endocarditis caused by the mucoid strain 144MR was associated with a
      significant reduction in intravegetation pseudomonal counts (P less than 0.05),
      to levels similar to that seen with endocarditis caused by the nonmucoid strain.
      In left-sided endocarditis caused by mucoid strain 144MR, animals received either
      no therapy, amikacin (20 or 40 mg/kg twice a day for 7 or 14 days), or amikacin
      plus alginase (750 U/day [i.v.]). The coadministration of alginase for 14 days
      with the higher-dose amikacin regimen rendered more left-sided vegetations
      culture negative than those in animals receiving the antibiotic alone for 7 or 14
      days (P = 0.001 and 0.056, respectively). These salutary effects of alginase in
      vivo were paralleled by the ability of the enzyme to remove the exopolysaccharide
      from the surface of mucoid pseudomonal cells within cardiac vegetations, as
      assessed by transmission electron microscopy.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1398910
TI  - Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism
      of type III group B streptococci.
AB  - Strains of type III group B streptococci isolated from patients with neonatal
      sepsis are generally resistant to complement-mediated phagocytic killing in the
      absence of specific antibody. It has been suggested that the resistance of type
      III group B streptococci to phagocytosis results from inhibition of alternative
      complement-pathway activation by sialic acid residues of the type III
      polysaccharide. To better define the relationship between structural features of
      the type III capsule and resistance of type III group B streptococci to
      complement-mediated phagocytic killing, we measured deposition of human C3 on
      group B streptococcal strains with altered capsule phenotypes. C3 binding was
      quantified by incubating bacteria with purified human 125I-C3 in 10% serum. Wild
      type group B Streptococcus sp. strain COH1 bound eightfold fewer C3 molecules
      than did either of two isogenic mutant strains, one expressing a sialic acid
      deficient capsule and the other lacking capsule completely. Similar results were
      obtained when the incubation with 125I-C3 was performed in serum chelated with Mg
      ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'- tetraacetic acid (MgEGTA),
      suggesting that the majority of C3 deposition occurred via the alternative
      pathway. In contrast to the wild-type strain, which was relatively resistant,
      both mutant strains were killed by human leukocytes in 10% serum with or without
      MgEGTA. We also measured C3 binding to 14 wild-type strains of type III group B
      streptococci expressing various amounts of capsule. Comparison of degree of
      encapsulation with C3 binding revealed a significant inverse correlation (r = 
      0.72; P less than 0.01). C3 fragments released by methylamine treatment of wild
      type strain COH1 were predominantly in the form of C3bi, while those released
      from the acapsular mutant were predominantly C3b and those from the asialo mutant
      represented approximately equal amounts of C3b and C3bi. We conclude from these
      studies that the sialylated type III capsular polysaccharide inhibits alternative
      pathway activation, prevents C3 deposition on group B streptococci, and protects
      the organisms from phagocytic killing.

PMID- 1398911
TI  - Characterization of a Salmonella typhimurium aro vaccine strain expressing the
      P.69 antigen of Bordetella pertussis.
AB  - The P.69 Bordetella pertussis protective antigen was expressed by use of the trc
      promoter from the chromosome of a Salmonella typhimurium aro vaccine strain,
      BRD509, by integrating the prn gene, encoding the 93-kDa precursor of this
      protein, into the aroC locus. P.69 was detected on the cell surface of the S.
      typhimurium strain (BRD640) by agglutination and immunoelectron microscopy.
      BALB/c mice immunized orally or intravenously with BRD640 showed a significant
      level of protection against an aerosol challenge with virulent B. pertussis,
      compared with control animals. No anti-P.69 antibodies in the serum or anti-P.69
      antibody-secreting cells in the lungs were detected in BRD640-vaccinated animals,
      although cells isolated from spleens showed a P.69-dependent cell proliferative
      response. In contrast, low levels of anti-P.69 antibodies in the serum and anti
      P.69 antibody-secreting cells in the lungs were detected in immunized mice
      following a B. pertussis challenge.

PMID- 1398912
TI  - Tumor necrosis factor and interleukin-6 in Candida albicans infection in normal
      and granulocytopenic mice.
AB  - We administered a neutralizing monoclonal antibody to tumor necrosis factor (TNF)
      during infection with Candida albicans in normal and granulocytopenic mice. Mice
      were rendered granulocytopenic (less than 0.1 x 10(9) granulocytes per liter)
      with cyclophosphamide. Growth of C. albicans from the kidneys was significantly
      increased in normal mice treated with the antibody to TNF, compared with that in
      control mice, after 36 h (3.6 x 10(4) +/- 1.2 x 10(4) CFU per kidney versus 9.1 x
      10(3) +/- 6.2 x 10(3) CFU per kidney; P less than 0.05) and after 72 h (3.7 x
      10(6) +/- 2.7 x 10(6) CFU per kidney versus 2.3 x 10(4) +/- 1.3 x 10(4) CFU per
      kidney; P less than 0.01). In granulocytopenic mice, the antibody to TNF had no
      effect on the growth of C. albicans from the kidneys. Furthermore, our study
      showed that the cytokines TNF and interleukin-6 (IL-6) were produced in a dose
      dependent manner during C. albicans infection. TNF was detectable between 6 and
      60 h, with peak levels at 24 h. Both TNF and IL-6 levels were significantly
      higher in cyclophosphamide-treated mice than in normal mice. Heat-inactivated C.
      albicans induced a TNF response different from that induced by viable C.
      albicans, with an early peak occurring at 3 to 4 h and declining to non
      detectable levels after 15 to 24 h. Peak levels of TNF obtained with heat
      inactivated C. albicans were lower than those obtained with viable C. albicans.
      Our study demonstrates that TNF and IL-6 are produced systemically during C.
      albicans infection and suggests that TNF is essential for granulocyte antifungal
      activity in vivo.

PMID- 1398913
TI  - Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine.
AB  - Group B streptococci (GBS) are the most common cause of bacterial sepsis and
      meningitis in neonates in the United States. Although the capsular polysaccharide
      of GBS is an important virulence factor, it is variably immunogenic in humans. In
      this report, we have increased the immunogenicity of GBS type II polysaccharide
      by coupling it to tetanus toxoid (TT). Like other GBS capsular polysaccharides,
      the type II polysaccharide has side chains terminating in sialic acid. Controlled
      periodate oxidation of native II polysaccharide resulted in the conversion of 7%
      of sialic acid residues to an analog of sialic acid, 5-acetamido-3,5-dideoxy-D
      galactosyloctulosonic acid. TT was conjugated to free aldehyde groups created on
      the oxidized sialic acid residues by reductive amination. Serum from rabbits
      vaccinated with type II-TT conjugate (II-TT) vaccine contained antibodies
      specific to type II polysaccharide as well as to TT, whereas rabbits vaccinated
      with uncoupled native type II polysaccharide failed to produce a type-specific
      antibody response. Antibodies elicited by II-TT vaccine were serotype specific
      and mediated phagocytosis and killing in vitro of type II GBS by human peripheral
      blood leukocytes. Serum from rabbits vaccinated with II-TT vaccine provided 100%
      protection in a mouse model of GBS type II infection. Antibodies induced by II-TT
      vaccine were specific for the native but not desialylated type II polysaccharide,
      suggesting that an important antigenic epitope of II-TT vaccine was dependent on
      the presence of sialic acid. Therefore, the coupling strategy which selectively
      modified a portion of the sialic acid residues of types II polysaccharide before
      coupling the polysaccharide to TT preserved the epitope essential to protective
      immunity and enhanced the immunogenicity of the polysaccharide.

PMID- 1398914
TI  - Immunoelectron microscopic studies reveal differences in distribution of sialo
      oligosaccharide receptors for Mycoplasma pneumoniae on the epithelium of human
      and hamster bronchi.
AB  - Long-chain sialo-oligosaccharides with poly-N-acetyllactosamine backbones (Ii
      antigen type) are major host cell receptors for the human pathogen Mycoplasma
      pneumoniae. Previous immunofluorescence studies of the human bronchial
      epithelium, using sequence-specific monoclonal antibodies to the branched I-type
      and linear i-type backbones, have indicated that sialylated and nonsialylated
      long-chain sequences of both types are richly expressed on the ciliated cells,
      where they are polarized at the apical aspects. These sequences are lacking in
      the goblet cells. In the present study, the display of these oligosaccharides has
      been investigated by electron microscopy (immunogold labelling) in the human
      bronchial epithelium and in that of the hamster, an animal model commonly used
      for M. pneumoniae infection. In the human bronchial epithelium, the long-chain
      branched sequences have been detected along the entire length of the cilia and on
      microvilli, whereas the linear sequences are confined to the microvilli and the
      basal aspects of the cilia. On the ciliated epithelial cells of the hamster, by
      contrast, the branched and linear sequences (sialo- and asialo-) have been
      detected exclusively on microvilli. A further striking difference is that in the
      hamster these structures are expressed in abundance on the goblet cells and in
      the intracellular globules. We suggest that the latter finding may partly explain
      the relatively large doses of M. pneumoniae required to establish experimental
      infection in the hamster, as the receptor-bearing secreted mucus may have a
      protective role in binding to the microorganisms, leading to their clearance by
      bronchociliary action.

PMID- 1398915
TI  - Identification and characterization of a surface protein-releasing activity in
      Streptococcus mutans and other pathogenic streptococci.
AB  - Surface proteins of Streptococcus mutans have been reported to be released into
      the culture filtrate at concentrations that vary with the growth conditions. The
      reason for this is not clear. The present study attempts to investigate the
      mechanism of the protein release. The results showed that whole cells and
      raffinose-stabilized protoplasts of S. mutans NG8, when incubated in buffers,
      were capable of releasing their surface proteins in a pH-dependent manner with
      optimal release at pH 5 to 6. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis revealed that the released proteins were very complex.
      Two proteins, adhesin P1, which has been previously shown to interact with a
      human salivary agglutinin, and glucosyltransferase have been identified among the
      released proteins. The release of adhesin P1 and other proteins was found to be
      inhibited by heat, Cu2+,Zn2+, and thiol-blocking reagents. The inhibition by heat
      and Cu2+ was irreversible, whereas that by the thiol-blocking reagents was
      reversible. EDTA, phenylmethylsulfonyl fluoride, and N-p-tosyl-L-lysyl
      chloromethyl ketone had no effect on the release of P1, indicating that the
      release was probably not due to proteolytic activity. Adhesin P1 from Cu(2+)
      inactivated S. mutans NG8 protoplasts could be released by mixing with fresh
      whole cells and protoplasts, but not the culture filtrate, of a P1-negative
      mutant of NG8, suggesting that the enzyme is located on the cell surface. This P1
      releasing activity was also detected in two other strains of S. mutans and one
      strain each of S. gordonii, S. agalactiae, S. pneumoniae, and S. pyogenes. The
      biological role(s) of this enzyme activity remains to be determined. However,
      owing to its ability to release virulent surface proteins from the cell, it may
      play an important role in cell surface modulation among the pathogenic
      streptococci.

PMID- 1398916
TI  - Identification of tumor necrosis factor as a transcriptional regulator of the
      phosphoenolpyruvate carboxykinase gene following endotoxin treatment of mice.
AB  - The decreased synthesis of hepatic phosphoenolpyruvate carboxykinase (PEPCK), the
      rate-limiting enzyme of gluconeogenesis, that occurs during endotoxemia was shown
      previously in rats to occur at the transcriptional level. In the current study,
      the exogenous administration of human recombinant tumor necrosis factor (TNF), a
      proximal mediator of endotoxic shock, reduced the PEPCK transcription rate,
      mRNAPEPCK levels, and PEPCK enzyme activity in a time- and dose-dependent manner
      in CD-1 mice. Comparable amounts of circulating TNF were measured in mice 2 h
      after injection of human recombinant TNF (10(5) U) or a 50% lethal dose of
      Escherichia coli endotoxin (20 mg/kg). Direct action of TNF to decrease the PEPCK
      transcription rate was confirmed in vitro with H-4-II-E Reuber hepatoma cells, in
      which a dose-dependent inhibition of PEPCK transcription was observed with 1 to
      100 U of TNF per ml. A role for TNF-elicited changes in PEPCK gene expression
      during endotoxemia was confirmed by the protective effect of rabbit polyclonal
      antibodies to recombinant murine TNF. C57BL/6 mice passively immunized with anti
      TNF 4 h prior to endotoxin challenge exhibited normal PEPCK enzyme activity.
      Neutralization of circulating TNF with anti-TNF failed, however, to prevent the
      hypoglycemia commonly observed during endotoxemia, suggesting the participation
      of other mediators. Anti-TNF treatment reduced circulating interleukins 1 and 6
      at 3 and 6 h after endotoxin treatment, respectively. These results suggest that
      during endotoxemia, the development of hypoglycemia is multifaceted and that
      several cytokines are most likely involved. The findings from the Reuber hepatoma
      cell model afford an opportunity in future work to map putative cytokine response
      elements in the PEPCK promoter responsible for perturbed hormonal regulation of
      the gene during endotoxemia.

PMID- 1398917
TI  - Adhesion to and invasion of cultured human cells by Bartonella bacilliformis.
AB  - Bartonella bacilliformis was tested for its ability to adhere to and invade
      tissue culture cell monolayers. The parasite was able to efficiently bind and
      penetrate human dermal fibroblasts, human laryngeal epithelium, and human
      umbilical vein endothelial cells. Exposure of the organism to immune serum
      prepared against a crude Bartonella extract containing cell wall and membranous
      material resulted in decreased ability of the parasite to invade host cells.
      There was also an overall reduction in the invasiveness of bartonellae and total
      host cell association when human laryngeal epithelial cells and human umbilical
      vein endothelial cells were preexposed to cytochalasin D, indicating an active
      involvement of host cells in the uptake of bartonellae. Transmission electron
      microscopy revealed the presence of bartonellae inside and outside intracellular
      vacuoles. These data suggest that a surface-associated factor is involved in the
      invasion process and that internalization of the parasite by host cells involves
      a microfilament-dependent process similar to phagocytosis.

PMID- 1398918
TI  - Purification and characterization of Listeria monocytogenes phosphatidylinositol
      specific phospholipase C.
AB  - We have purified to homogeneity the 33-kDa phosphatidylinositol-specific
      phospholipase C (PI-PLC) from the culture fluid of Listeria monocytogenes, a
      facultative intracellular pathogen. The protein was overexpressed, and secretion
      of PI-PLC was further enhanced by the addition of divalent cations to the culture
      medium. The basic protein (pI, approximately 9.4) was complexed with anionic
      proteins in the crude culture fluid. It bound to DEAE-Sepharose and was eluted
      from Sephacryl S-200 near the void volume in low-ionic-strength buffer,
      suggesting aggregates of greater than or equal to 150 kDa. Gel filtration
      chromatography on Sephacryl S-200 in the presence of 1 M ammonium sulfate
      resulted in disaggregation and complete separation of PI-PLC, which interacted
      with the column matrix. Amino-terminal sequencing of the pure protein gave
      results consistent with the previously deduced sequence and showed that the
      signal cleavage site was between alanine 29 and tyrosine 30. The enzyme was
      specific for PI and showed no activity with phosphatidylethanolamine,
      phosphatidylcholine, or phosphatidylserine. It did not cleave PI-4-phosphate or
      PI-4,5-bisphosphate, but it was active on the membrane form of the variable
      surface glycoprotein from Trypanosoma brucei, a PI-glycan-anchored protein. When
      assayed with deoxycholate-mixed micelles of PI, activity was highly dependent on
      added salt. Activation by salt was also observed with Triton X-100-mixed
      micelles. The optimal concentration of CaCl2 or MgCl2 was lower than that of KCl
      or (NH4)2SO4, but activity was not specifically dependent on divalent cations and
      was not inhibited by addition of EDTA. With deoxycholate, the optimum pH was 7.0.
      A broader pH optimum ranging from 5.5 to 6.5 was observed with Triton X-100-mixed
      micelles. These results are consistent with a postulated role for secreted PI-PLC
      in the acidified primary phagocytic vesicle of infected cells.

PMID- 1398919
TI  - Early expression of cytokine mRNA in mice infected with Listeria monocytogenes.
AB  - Protective immunity first becomes evident at 3 to 4 days after inoculation of
      mice with a sublethal dose of Listeria monocytogenes. Recent evidence suggests
      that production of gamma interferon (IFN-gamma) occurs earlier (within the first
      24 h of infection). The purpose of this study was to define better the sequence
      of cytokine mRNA expression during the early stages of L. monocytogenes
      infection. Cytokine mRNA expression was detected by polymerase chain reaction
      assisted amplification of RNA extracted from the spleen cells of individual mice
      euthanized at 0.5 to 120 h after L. monocytogenes challenge. By using this
      method, mRNAs for tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha),
      IL-2, IL-4, IL-5, and IFN-gamma were detected in RNA from the spleen cells of
      uninfected mice. The intensity of the bands for IFN-gamma, however, was increased
      greatly at 16 h after intravenous injection of 5 x 10(4) CFU (nearly 1 50% lethal
      dose) of L. monocytogenes. IL-6 and granulocyte-macrophage colony-stimulating
      factor mRNAs were not detected in spleen cell RNA from uninfected mice but were
      induced within 30 and 60 min, respectively, after inoculation with L.
      monocytogenes. Increased amounts of mRNAs for IFN-gamma, IL-6, and granulocyte
      macrophage colony-stimulating factor were detected after injection of viable, but
      not killed, L. monocytogenes. IL-3 mRNA was not detected at any time in RNA
      extracted from the spleen cells of uninfected or L. monocytogenes infected mice.
      These results suggest that infection with L. monocytogenes elicits a detectable
      cytokine mRNA response within the first few hours of infection.

PMID- 1398920
TI  - Experimental infection of severe combined immunodeficient beige mice with
      Mycobacterium paratuberculosis of bovine origin.
AB  - Severe combined immunodeficient beige mice were inoculated orally and
      intraperitoneally with a bovine strain of Mycobacterium paratuberculosis to
      explore their potential as laboratory animal models in the study of
      paratuberculosis (Johne's disease). Control animals were similarly inoculated
      with heat-killed M. paratuberculosis. In the mice inoculated intraperitoneally,
      focal lesions and acid-fast bacilli were first detected in the livers (4 weeks
      postinfection) and later in the spleens and intestines of the test but not the
      control animals. No bacteria were seen in the hearts, kidneys, or lungs. At 12
      weeks postinfection, all test mice had significant losses in body weight compared
      with those in controls (P less than 0.05), a characteristic sign of bovine
      paratuberculosis. Tumor necrosis factor alpha was not detected in the serum.
      Histologic lesions were seen in the intestines, livers, and spleens of the
      animals in the orally inoculated test group after 26 weeks of infection. Our
      results suggest that the severe combined immunodeficient beige mouse may be a
      useful model for the investigation of paratuberculosis and cachexia and the
      evaluation of antimycobacterial drugs.

PMID- 1398921
TI  - The glucuronoxylomannan of Cryptococcus neoformans serotype A is a type 2 T-cell
      independent antigen.
AB  - The humoral immune response of inbred mice to immunization with the
      glucuronoxylomannan (GXM) of Cryptococcus neoformans was investigated both
      serologically and in plaque-forming cells (PFCs). The T-helper-cell-independent
      quality of the GXM was demonstrated by using BALB/c nu/nu mice. Primary and
      secondary dose responses to three antigenic forms of GXM, (i) the native antigen,
      (ii) a GXM-bovine serum albumin protein conjugate, and (iii) a cryptococcal whole
      cell vaccine, revealed a lack of isotype class switching and anamnestic
      responses. Both the levels of complement-fixing anti-GXM antibody in serum and
      the PFC responses in the athymic mice showed no significant differences from
      those in the wild-type controls. However, T cells are involved in the suppression
      of the primary response to GXM. When BALB/cBy mice were given rabbit anti-mouse
      thymocyte serum along with 0.5 microgram of GXM, both antibody levels in serum
      and PFC responses were significantly increased over those of control mice that
      received GXM and normal rabbit serum. In addition, T cells were also shown to
      enhance the primary immune response to GXM. BALB/cBy mice were given GXM and anti
      mouse thymocyte serum on day 1. On day 2, the experimental group was given anti
      mouse thymocyte serum and the control group was given saline. On day 5,
      comparison of the PFC responses and anti-GXM antibody titers of the two groups
      revealed a significant increase in the immune response of the control over the
      experimental group. The type 2 T-cell-independent quality of GXM was also
      demonstrated in CBA/cHN xid mice. These mice lack the Lyb+ subset of B cells and
      are unable to respond to type 2 T-independent antigens but respond normally to
      type 1 T-independent antigens. Type III pneumococcal polysaccharide, a type 2 T
      independent antigen, was used as a negative control, and trinitrophenyl
      lipopolysaccharide, a type 1 T-independent antigen, was used as a positive
      control. The CBA/cHN xid mice failed to respond to either type III pneumococcal
      polysaccharide or GXM but did not respond to immunization with trinitrophenyl
      lipopolysaccharide. BALB/cBy mice responded normally to all three antigens.

PMID- 1398922
TI  - Unipolar reorganization of F-actin layer at bacterial division and bundling of
      actin filaments by plastin correlate with movement of Shigella flexneri within
      HeLa cells.
AB  - Shigella flexneri causes bacillary dysentery, an invasive disease of colonic
      epithelial cells in humans. The capacity of bacteria, once they have entered into
      a cell and escaped the phagocytic vacuole, to spread intracellularly and directly
      to adjacent cells without further extracellular passage is a key factor in
      invasion of the epithelial layer. Movement of intracellular bacteria is dependent
      upon the polymerization of actin; concentration of the formed filaments to one
      end of the bacterium is associated with initiation of movement. This movement may
      lead to the formation of a protrusion at the cell surface through which the
      bacterium passes to an adjacent cell. Development of these protrusions in
      infected HeLa cells is described, with emphasis on two critical observations.
      First, initiation of movement is coupled with bacterial division since elongation
      of the bacterial body is associated with relocalization of the previously
      uniformly distributed layer of actin to one pole of the bacterium. Second, the
      actin-bundling protein plastin appears to bundle the actin filaments just
      posterior to the bacterium, producing an ongoing contraction of the cylindrical
      actin tail that may be associated with forward movement of the bacterium within
      the protrusion.

PMID- 1398923
TI  - Genetic relationships of penicillin-susceptible and -resistant Streptococcus
      pneumoniae strains isolated on different continents.
AB  - Sixty-six strains of Streptococcus pneumoniae isolated in different parts of the
      world, 46 resistant and 22 susceptible to penicillin, were subdivided by
      multilocus enzyme electrophoresis into 28 distinct electrophoretic types (ETs).
      The ETs to which penicillin-susceptible strains were assigned differed from those
      containing resistant isolates of the same serotype. Five common clones could be
      recognized among the penicillin-resistant bacteria by combining the ETs, the
      antigenic properties of penicillin-binding proteins PBP 1a and 2b, and the
      tetracycline and chloramphenicol resistance profiles. Two clones were found in
      Finland and were associated with capsular serotypes 6B and 23F, respectively. Two
      clones were from Spain (type 6B and 9V, respectively). The fifth clone was
      isolated in South Africa and in Spain and contained both serotype 23F isolates
      and one type 19F strain. The other resistant strains were represented by rare
      isolates distributed among 12 other ETs, confirming that resistance to penicillin
      has evolved by multiple branches. Because capsular type was mixed in several ETs,
      the results also demonstrate that it may vary among very closely related
      pneumococci.

PMID- 1398924
TI  - Staphylococcus saprophyticus hemagglutinin is a 160-kilodalton surface
      polypeptide.
AB  - Many strains of Staphylococcus saprophyticus cause direct hemagglutination of
      sheep erythrocytes. For a high proportion of clinical isolates, a surface protein
      (Ssp) that is apparently not involved in this property has been described. In
      this study, S. saprophyticus CCM883, a hemagglutinating but Ssp-negative strain,
      was used for the identification, purification, and characterization of a 160-kDa
      surface polypeptide that appears to be the major component of the hemagglutinin.
      Expression of the protein required the addition to the growth medium of EDTA in
      micromolar quantities, suggesting an inhibitory role for some unidentified metal
      ion. The protein was purified by means of Sephacryl S-300 chromatography, and
      antisera were raised in rabbits. Antibody against this protein inhibited the
      hemagglutination of two other, unrelated strains and was used to demonstrate, by
      electron microscopy, the presence of the protein on the surface of the cells. In
      a confirmatory experiment, the purified antigen was incubated with erythrocytes
      and binding was detected by the Western immunoblot technique with the antibody to
      the 160-kDa polypeptide. These experiments indicate that this surface protein is
      the hemagglutinin of S. saprophyticus.

PMID- 1398925
TI  - SCID-Hu mice immunized with a pneumococcal vaccine produce specific human
      antibodies and show increased resistance to infection.
AB  - Seventy-eight severe combined immunodeficiency (SCID) mice were administered
      intraperitoneally 1 x 10(7) to 9 x 10(7) human peripheral blood mononuclear cells
      (PBL) in five experiments. Human immunoglobulin G (IgG) was detected in 70 to 88%
      of these SCID-PBL-Hu mice after cell transplantation, and all four subclasses
      were present. The total concentration of human IgG varied from less than 1 to
      10.2 g/liter. The SCID-PBL-Hu mice with high concentrations of human IgG
      regularly had mono- or oligoclonal human IgG bands in serum, as demonstrated by
      agarose gel electrophoresis. Of the SCID-PBL-Hu mice that were immunized with a
      23-valent pneumococcal polysaccharide vaccine, 63 to 78% developed a significant
      human IgG antipneumococcal antibody response, whereas only very low levels of
      human IgM and no human IgA antipneumococcal antibodies could be detected. Twelve
      to twenty-two percent of the SCID-PBL-Hu mice showed signs of leakiness; these
      mice developed a significant mouse IgM antipneumococcal antibody response and no
      human antibodies. SCID-PBL-Hu mice were challenged intraperitoneally with 10 50%
      lethal doses of Streptococcus pneumoniae serotype 4 to study the protective
      effect of immunization with pneumococcal vaccine. The immunized SCID-PBL-Hu mice
      showed less bacteremia than did all control groups, and survival was 45 to 60%.
      None of the unimmunized SCID-PBL-Hu mice survived.

PMID- 1398926
TI  - Experimental verocytotoxemia in rabbits.
AB  - The clinicopathologic effects of intravenously administered purified
      verocytotoxin 1 (VT1; Shiga-like toxin 1) in 2-kg male rabbits was studied. The
      50% lethal dose was 0.2 micrograms of protein per kg of body weight (2 x 10(4)
      50% cytotoxic doses per kg). The clinical features included nonbloody diarrhea
      and a progressive flaccid paresis, usually culminating in death. The
      histopathology was characterized by edema and hemorrhage in the mucosa and
      submucosa of the cecum and edema, hemorrhage, and neuronal necrosis in the brain
      and gray matter of the spinal cord. Thrombotic microangiopathy, the
      characteristic histopathologic renal lesion in the hemolytic-uremic syndrome, was
      also found to be the underlying lesion in verocytotoxemic rabbits. To determine
      the specific distribution of VT1 in rabbit tissues, purified 125I-labelled VT1
      was administered intravenously to 20 rabbits (both immunologically naive and VT1
      immune rabbits). The highest specific uptake of 125I-VT1 was in the spinal cord,
      brain, cecum, colon, and small bowel in unimmunized animals but in the liver,
      spleen, and lungs in immune animals. Immunofluorescent staining of cecal and
      spinal cord tissues after intravenous administration of VT1 showed evidence of
      specific vascular endothelial cell binding of the toxin. The striking correlation
      of the central nervous system and gastrointestinal localization of 125I-VT1 with
      the sites of known histopathology is consistent with direct toxin-mediated injury
      to these tissues, initiated by the specific binding of VT1 to the vascular
      endothelium. We conclude that the vascular damage induced by VT1 in affected
      rabbit tissues is similar to that seen in the kidneys and other tissues in
      patients with verocytotoxin-producing Escherichia coli-associated hemolytic
      uremic syndrome. This suggests that although the rabbit model fails to replicate
      human hemolytic-uremic syndrome, it is useful for studying the pathogenesis of
      the vascular lesions in verocytotoxin-producing E. coli-associated diseases.

PMID- 1398927
TI  - Retrovirus-induced immunodeficiency in mice exacerbates gastrointestinal
      candidiasis.
AB  - Dysfunction of neutrophils in patients infected with human immunodeficiency virus
      is at least partly responsible for secondary microbial diseases in these
      individuals, including invasive gastrointestinal (GI) candidiasis.
      Immunoregulatory disturbances associated with the development of AIDS in human
      immunodeficiency virus-infected patients exacerbates Candida albicans infection
      of the upper GI tract and frequently leads to oropharyngeal and esophageal
      candidiasis. In this article, we present the first report of a murine model of
      invasive GI candidiasis associated with an AIDS-related murine immunodeficiency
      syndrome that results from infection of C57BL/6 mice with a previously described
      retrovirus complex (LP-BM5). Mice of the inbred strain were infected with C.
      albicans by oral-intragastric inoculation as infants and with the retrovirus by
      the intraperitoneal route 30 days later. Control mice of the same strain were
      infected with C. albicans as above and subsequently infected with the avirulent,
      ecotropic helper virus (MBI-5). Animals were killed 90 days after retroviral
      challenge. Total and differential blood cell counts, CD4+ T-cell counts in the
      spleen, and the histopathology of the gastric mucosa of experimental and control
      animals were determined. The virulent LP-BM5-infected animals developed murine
      AIDS and showed eruptive and suppurative lesions, with associated C. albicans
      mainly in regions of the cardial-atrium fold of the stomach. Well-defined
      abscesses with entrapped C. albicans hyphae were observed in the region of the
      cardial-atrium fold of control mice. A significant increase in the number of C.
      albicans CFU in homogenized and plated segments of the GI tract was recognized in
      mice with murine AIDS versus the control animals. The murine model of GI
      candidiasis reported here permits examination of the nature of C. albicans
      interaction with the gastric mucosa both in the immunocompetent host under
      conditions in which the yeast exists predominantly as a commensal organism and in
      the immunosuppressed host during progressive stages of AIDS induced by a
      retroviral infection.

PMID- 1398928
TI  - Induction of procoagulant activity on human endothelial cells by Streptococcus
      pneumoniae.
AB  - The inflammatory response in infection caused by gram-negative organisms involves
      induction of procoagulant activity (PCA) on human endothelial cells. Although
      infections caused by gram-positive organisms are also associated with fibrin
      formation and thrombosis, the bacterial determinants inducing PCA are unknown.
      This study shows that intact pneumococci and the pneumococcal cell wall
      efficiently induce PCA on human endothelial cells. Upon exposure of endothelial
      cells to pneumococci, PCA was first detectable at 30 min, peaked at 2 h, and
      disappeared by 6 h. The specific activities of encapsulated and unencapsulated
      strains for induction of PCA were equivalent. Purified pneumococcal cell walls
      were as potent as endotoxin in induction of PCA. The ability to induce a
      procoagulant state on endothelial cells is a new biological activity of gram
      positive cell walls which promotes the participation of the coagulation cascade
      in the inflammatory response to disease caused by gram-positive organisms.

PMID- 1398929
TI  - Immunocytological responses in porcine proliferative enteropathies.
AB  - The ileum, colon, and mesenteric lymph nodes of pigs naturally affected by either
      of the two major forms of proliferative enteropathy, namely, intestinal
      adenomatosis or hemorrhagic enteropathy, were examined for immunocytological
      responses to infection by immunocytochemistry, using antibodies directed against
      elements of the porcine immune system. In both forms, there was mucosal
      proliferation of immature enterocytes which lacked substantial major
      histocompatibility complex class II expression and a marked accumulation of
      immunoglobulin A (IgA) at the apical cytoplasm of affected enterocytes in
      association with intracellular Campylobacter-like organisms. In intestinal
      adenomatosis, there was only a mild infiltration of CD8+ and CD25+ T cells in the
      intestinal lamina propria. In hemorrhagic enteropathy, there was a moderate
      infiltration of CD8+ and CD25+ T cells and IgM+ B cells in the lamina propria. In
      rats and humans, villous enterocytes are thought to act as antigen-presenting
      cells, with major histocompatibility complex class II molecules present on their
      surface, capable of initiating a T-cell response (particularly of CD8+ T cells)
      in response to bacterial antigens. Therefore, the selection of immature crypt
      cells by the intracellular Campylobacter-like organisms for entry and
      multiplication may represent a remarkable microbial adaptation associated with
      local immunomodulation and enhanced bacterial survival. The accumulation of IgA
      within affected enterocytes may represent a reduced capability of the cells to
      process nonspecific IgA or an accumulation of specific IgA.

PMID- 1398930
TI  - Molecular, immunological, and biological characterization of a toxin A-negative,
      toxin B-positive strain of Clostridium difficile.
AB  - A cytotoxigenic Clostridium difficile strain that fails to produce toxin A but
      causes hemorrhage and bloody fluid accumulation in ligated ileal loops of rabbits
      and hemorrhage and diarrhea in hamsters is described. The lack of reaction of DNA
      from this strain in hybridization studies with a toxin A gene-specific 4.5-kb
      probe and polymerase chain reaction studies with six toxin A-specific primers
      indicate the absence of the toxin A gene. The cytotoxin produced by this strain
      was not responsible for the enterotoxic or hemorrhagic activity and shared
      characteristics with toxin B, i.e., its cytotoxicity was neutralized by
      antibodies to toxigenic strains of C. difficile and Clostridium sordellii.
      Polymerase chain reaction studies with toxin B-specific primers showed that the
      DNA from this strain produced a 690-bp product in addition to the expected 591-bp
      product.

PMID- 1398931
TI  - Killing of Coccidioides immitis by human peripheral blood mononuclear cells.
AB  - The ability of human peripheral blood mononuclear cells (MNL) obtained from
      healthy donors to kill the fungus Coccidioides immitis was examined in vitro with
      an assay that uses a single fungal particle per well. MNL killed 25.0% +/- 3.5%
      of a coccidioidal arthroconidial target, compared with the 4.7% +/- 2.9% killed
      by polymorphonuclear leukocytes obtained from the same donors (P = 0.012).
      Arthroconidial killing by MNL was not dependent on donor delayed dermal
      hypersensitivity to spherulin. Killing of another fungal target, Candida
      glabrata, was not significantly different between MNL and polymorphonuclear
      leukocytes (P = 0.783). Depletion of monocytes from MNL with Sephadex G-10
      resulted in a significant reduction in arthroconidial killing (21.4% +/- 13.6%
      versus 2.4% +/- 3.4%; P = 0.025), while enrichment of monocytes by Percoll
      density gradient centrifugation or plastic adherence resulted in significantly
      increased arthroconidial killing compared with that by MNL (P = 0.005 and 0.001,
      respectively). Killing of 96-h spherules by MNL was 7.3% +/- 3.1%, significantly
      less than the 21.4% +/- 2.8% killing of arthroconidia in the same experiments (P
      = 0.016). Incubation of MNL with human recombinant gamma interferon or tumor
      necrosis factor alpha did not result in increased MNL killing of coccidioidal
      arthroconidia under various conditions. These results suggest that MNL have an
      inherent ability to kill coccidioidal arthroconidia in vitro which is not
      dependent on prior host exposure to C. immitis. This activity appears to reside
      in peripheral blood monocytes.

PMID- 1398932
TI  - Coiling phagocytosis is the preferential phagocytic mechanism for Borrelia
      burgdorferi.
AB  - The uptake mechanism for the spirochete Borrelia burgdorferi, the causative agent
      of Lyme disease, was investigated by electron microscopy for human and murine
      phagocytes. Spirochetes of both a low- and a high-passage strain were
      preferentially internalized by coiling rather than by conventional phagocytosis.
      The spirochetes engulfed by coiling phagocytosis were found to disintegrate in an
      organelle exclusion zone without evident participation of lysosomes.
      Preincubation of B. burgdorferi with monoclonal antibody to the spirochetal OspA
      enhanced phagocytosis in general but did not consistently influence the uptake
      mechanism. Quantitative and kinetic differences concerning the phagocytic rate
      and mechanism were evident between cells from different lineages, different human
      individuals, and mice and humans. In general, when few phagocytes participated in
      spirochete uptake, the active cells displayed a high ratio of coiling versus
      conventional phagocytosis. These results suggest that coiling phagocytosis of B.
      burgdorferi plays a critical role in the control of spirochetal infection. More
      detailed studies on the molecular basis of this phagocytic mechanism may lead to
      new insights into the pathogenesis of Lyme borreliosis, a disease which is
      frequently characterized by the host's inability to eliminate the pathogenic
      spirochete.

PMID- 1398933
TI  - Identification of a 58-kilodalton cell surface fibrinogen-binding mannoprotein
      from Candida albicans.
AB  - Treatment of both yeast (blastoconidia) and hyphal (blastoconidia with germ
      tubes) cells of Candida albicans with beta-mercaptoethanol (beta ME) releases a
      complex array of cell wall-bound proteins and glycoproteins. Analysis by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting
      with fibrinogen-anti-fibrinogen antibody allowed the identification of a 58-kDa
      mannoprotein (mp58) in both extracts which specifically interacts with human
      fibrinogen. Treatment of intact cells with low concentrations of beta-glucanase
      (Zymolyase 20T) for short periods or with beta ME abolished or significantly
      reduced binding of fibrinogen. A rabbit polyclonal antiserum was raised against
      the purified mp58 species released by beta ME from germinated blastoconidia (PAb
      anti-mp58). By Western blotting, the antiserum cross-reacted with the homologous
      58-kDa fibrinogen-binding mannoprotein present in beta ME extracts from
      blastoconidia, and by indirect immunofluorescence, the antiserum labelled both
      yeast cells and hyphae, yet reactivity was found primarily on the cell surface of
      filamentous forms. Immunostaining of human infected tissue sections with PAb anti
      mp58 showed that the mp58 species is also expressed in vivo; in this case, the
      species is in the forms of both yeast and hyphal elements similarly labelled by
      the antiserum. Purified immunoglobulin G fraction from the antiserum did not
      alter the binding of fibrinogen as determined by a modified enzyme-linked
      immunosorbent assay and Western blotting. The N- and O-glycosidically linked
      carbohydrates represent 18 to 20% and 3 to 4%, respectively, of the molecular
      mass of the mp58. O-linked sugar residues may be involved in the interaction of
      the molecule with fibrinogen.

PMID- 1398934
TI  - Early activation of splenic macrophages by tumor necrosis factor alpha is
      important in determining the outcome of experimental histoplasmosis in mice.
AB  - Experimental infection of animals with Histoplasma capsulatum caused a massive
      macrophage infiltration into the spleen and induced the production of tumor
      necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in
      vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast
      cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha
      antibody was detrimental to sublethally infected mice. Fungous burdens in the
      spleens of TNF-alpha-depleted mice were higher than they were in the infected
      control mice at days 2, 7, and 9 after infection, and the antibody-treated
      animals succumbed to the infection. Histopathological study of spleen sections
      revealed that splenic macrophages were not able to control proliferation of
      intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha
      plays a role in early activation of splenic macrophages which is important in
      controlling the outcome of an infection.

PMID- 1398935
TI  - Similarity between the group B and A streptococcal C5a peptidase genes.
AB  - Group B streptococci (GBS) and group A streptococci (GAS) are known to have
      surface-associated peptidase activity which specifically cleaves C5a (C5a-ase),
      the primary chemotaxin for polymorphonuclear leukocytes. Amplification products
      were obtained from GBS genomic DNA template by using the polymerase chain
      reaction and primers corresponding to the C5a peptidase gene of GAS (scpA12). A
      restriction map of the GBS full-length amplified gene (scpB) was developed. The
      scpB restriction map was found to be highly similar to that of the analogous gene
      in GAS. A 50-bp deletion was located near the 5' end of scpB in a region where
      repeat sequences are found in scpA12. Hybridization experiments confirmed that
      other serotypes of GBS also carry an scpB-like gene. These results show that GBS
      contain a gene, scpB, which is very similar to that harbored by M12 GAS. The
      probability that scpB encodes the C5a-ase protein is discussed.

PMID- 1398936
TI  - Analysis of adhesion and cytotoxicity of Tritrichomonas foetus to mammalian cells
      by use of monoclonal antibodies.
AB  - The relationship of Tritrichomonas foetus adhesion to mammalian cells and
      cytotoxicity to these targets was investigated. High-adherence and low-adherence
      lines of T. foetus, derived by repeated adhesion to HeLa cells, showed high and
      low cytotoxicity, respectively, to HeLa cells. When parasites were separated from
      targets by membranes (0.4-microns pore size), no cytotoxicity was detectable.
      Monoclonal antibodies elicited against T. foetus that lowered adhesion also
      lowered parasite-mediated cytotoxicity. Flow cytometry experiments revealed that
      the levels of an adhesion- and cytotoxicity-blocking antibody bound to the
      surface of high-adherence clones of T. foetus were higher than those in low
      adherence clones. Western blots of parasite extracts separated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis were probed with an anti-T. foetus
      antibody. A molecule with a molecular weight of approximately 190,000 composed of
      subunits with molecular weights of approximately 140,000 to 150,000 and
      approximately 65,000 was identified. Immunoprecipitation experiments with
      metabolically labeled T. foetus and the same antibody confirmed that similar
      subunits were synthesized by the parasite. These results indicate that adhesion
      of T. foetus to mammalian cells is an important step in cytotoxic damage of these
      targets and that a surface adhesin on the parasite is involved in the adhesion
      mechanism.

PMID- 1398937
TI  - Specific lung mucosal and systemic immune responses after oral immunization of
      mice with Salmonella typhimurium aroA, Salmonella typhi Ty21a, and invasive
      Escherichia coli expressing recombinant pertussis toxin S1 subunit.
AB  - Pertussis toxin (PT) is considered an essential protective component for
      incorporation into new generation vaccines against Bordetella pertussis, the
      causative agent of whooping cough. Traditionally, antipertussis vaccination has
      employed an intramuscular route. An alternative to this approach is to stimulate
      mucosal and systemic immune responses by oral immunization with live vaccine
      carrier strains of Salmonella spp. or Escherichia coli. Recombinant S1 subunit of
      pertussis toxin was expressed in the attenuated aroA mutant of Salmonella
      typhimurium, SL3261, in the human typhoid vaccine strain Salmonella typhi Ty21a,
      and in E. coli CAG629 containing the Shigella flexneri plasmid pWR110, which
      encodes bacterial invasiveness of epithelial cells. Expression of recombinant PT
      S1 subunit (rPT-S1) did not affect in vitro invasiveness of the tested strains,
      which retained the ability to adhere to and invade the embryonic human intestinal
      cell line HI-407. Following oral immunization of mice with the live vaccine
      strains expressing rPT-S1, immunoglobulin G (IgG), IgA, and IgM responses were
      monitored. IgG specific to PT was detected in serum samples of mice, while IgG
      and IgA specific to PT were detected in lung washes after oral immunization with
      living Salmonella spp. or E. coli (pWR110) expressing rPT-S1. Utilization of live
      oral vaccines expressing B. pertussis antigens, which stimulate both a systemic
      and lung mucosal response, may provide an attractive alternative to purified
      component vaccines against whooping cough.

PMID- 1398939
TI  - Rhodopseudomonas sphaeroides lipid A derivatives block in vitro induction of
      tumor necrosis factor and endotoxin tolerance by smooth lipopolysaccharide and
      monophosphoryl lipid A.
AB  - Rhodopseudomonas (Rhodobacter) sphaeroides diphosphoryl lipid A is a relatively
      inert species of lipid A but has been shown to antagonize the effects of toxic
      lipopolysaccharide (LPS) both in vivo and in vitro. The antagonist and its
      monophosphoryl derivative were examined for the ability to block tumor necrosis
      factor synthesis and reverse tolerance induction in vitro in macrophage cultures
      stimulated with bioactive preparations of smooth LPS, rough LPS, diphosphoryl
      lipid A, and monophosphoryl lipid A. Inhibition of agonist activity and reversal
      of tolerance by these novel penta-acylated lipid A antagonists provides new
      insight into macrophage-LPS interactions.

PMID- 1398938
TI  - Role of Yersinia enterocolitica Yst toxin in experimental infection of young
      rabbits.
AB  - We constructed a Yst-negative mutant of Yersinia enterocolitica W1024 by reverse
      genetics, and we compared the virulence of the yst+ and yst isogenic strains in
      an experimental oral infection of the young rabbit. The rabbits infected with the
      yst+ strain suffered from the diarrhea and lost weight, and most of them died. By
      contrast, the occurrence of diarrhea, weight loss, and death in the group of
      rabbits infected with the yst mutant was as low as that in the group of
      uninfected rabbits. Bacteria from both strains were excreted in the feces and
      induced a serum antibody response against Yop proteins. The yst mutant
      disappeared more rapidly from the feces. We conclude that the enterotoxin Yst is
      a major factor involved in the Y. enterocolitica-associated diarrhea in the young
      rabbit. Given the similarity with the symptoms observed for children, this result
      suggests that Yst could also be an important factor in diarrhea in young children
      infected with Y. enterocolitica.

PMID- 1398940
TI  - Adhesion of glucosyltransferase phase variants to Streptococcus gordonii
      bacterium-glucan substrata may involve lipoteichoic acid.
AB  - Growing Streptococcus gordonii Spp+ phase variants, which have normal levels of
      glucosyltransferase (GTF) activity, use sucrose to promote their accumulation on
      surfaces by forming a cohesive bacterium-insoluble glucan polymer mass (BPM). Spp
      phase variants, which have lower levels of GTF activity, do not form BPMs and do
      not remain in BPMs formed by Spp+ cells when grown in mixed cultures. To test the
      hypothesis that segregation of attached Spp+ and unattached Spp- cells was due to
      differences in adhesiveness, adhesion between washed, [3H]thymidine-labeled cells
      and preformed BPM substrata was measured. Unexpectedly, the results showed that
      cells of both phenotypes, as well as GTF-negative cells, attached equally well to
      preformed BPMs, indicating that attachment to BPMs was independent of cell
      surface GTF activity. Initial characterization of this binding interaction
      suggested that a protease-sensitive component on the washed cells may be binding
      to lipoteichoic acids sequestered in the BPM, since exogenous lipoteichoic acid
      inhibited adhesion. Surprisingly, the adhesion of both Spp+ and Spp- cells was
      markedly inhibited in the presence of sucrose, which also released lipoteichoic
      acid from the BPM. These in vitro findings suggest that, in vivo, sucrose and
      lipoteichoic acid may modify dental plaque development by enhancing or inhibiting
      the attachment of additional bacteria.

PMID- 1398941
TI  - The 93-kilodalton protein of Borrelia burgdorferi: an immunodominant protoplasmic
      cylinder antigen.
AB  - Using immunoblots, we identified proteins of Borrelia burgdorferi recognized by
      sera from 62 patients with either acute or chronic Lyme disease. In all groups
      studied, the 41-kDa flagellar protein and a relatively minor 93-kDa protein (p93)
      were the most commonly recognized antigens in patients with acute and chronic
      disease due to B. burgdorferi. A murine monoclonal antibody (MAb 181.1) was
      developed against p93, and the antigen was detected by immunoblot analysis in
      four European and American strains of B. burgdorferi. On two-dimensional gel
      electrophoresis, p93 had an apparent pI of 6.8. Immunoelectronmicroscopy with MAb
      181.1 demonstrated that p93 is located within the protoplasmic cylinder
      compartment of the organism. The gene encoding p93 was retrieved from a phage
      expression library. The derived amino acid sequence of p93 confirmed chemical
      characterization of the antigen, including its amino-terminal peptide sequence.
      The derived amino acid sequence predicted it to be predominantly alpha helical. A
      prominent antigenic domain located at the carboxy portion of the protein was
      recognized by human and rabbit polyclonal antisera and human (MAb D4) and mouse
      (MAb 181.1) MAbs.

PMID- 1398943
TI  - Influence of Actinobacillus pleuropneumoniae serotype 2 and its cytolysins on
      porcine neutrophil chemiluminescence.
AB  - The effects of Actinobacillus pleuropneumoniae serotype 2 and its metabolites on
      the oxidative activity of porcine neutrophils were studied by using a
      chemiluminescence technique. Viable A. pleuropneumoniae stimulated the production
      of oxygen radicals by neutrophils. After having reached a peak value, the
      oxidative activity decreased until a total inhibition of the oxidative activity
      of the neutrophils was achieved. All effects were neutralized with homologous
      convalescent-phase pig sera which had been adsorbed by heat-inactivated A.
      pleuropneumoniae. Inactivated bacteria and bacteria in the presence of
      chloramphenicol each had no influence on the oxidative activity of neutrophils.
      In contrast, a heat-labile factor in A. pleuropneumoniae culture supernatants
      stimulated and inhibited the oxidative activity of the neutrophils in a dose
      dependent manner. Undiluted and low dilutions of culture supernatants were toxic
      for the phagocytes, while high dilutions stimulated the oxygen radical production
      of the neutrophils. These effects were neutralized with homologous convalescent
      phase pig sera. In order to investigate whether the heat-labile factors in the
      culture supernatant could be cytolysins, we repeated the experiments with
      cytolysin II and cytolysin III produced by recombinant Escherichia coli. It was
      demonstrated that stimulation and inhibition could be reproduced by both
      cytolysins. In conclusion, the observations made in this study showed that A.
      pleuropneumoniae secretes heat-labile metabolites that stimulate neutrophil
      oxidative metabolism at relatively low concentrations and kill the neutrophils at
      higher concentrations. Cytolysins may be responsible, at least in part, for these
      effects.

PMID- 1398942
TI  - Hemagglutination and adherence to plastic by Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is an important nosocomial pathogen responsible for
      intravenous catheter-related bacteremia and infections of other prosthetic
      medical devices. We found that the ability of S. epidermidis to hemagglutinate
      erythrocytes correlated with the adherence of bacteria to plastic and to
      intravenous catheters. S. epidermidis isolates responsible for prosthetic-valve
      endocarditis (n = 61) and isolates from intravenous catheters (n = 59) were
      significantly more likely to cause hemagglutination than isolates from the skin
      of preoperative cardiac surgery patients (n = 19) (P = 0.027). S. epidermidis
      isolates (n = 23) recovered from the skin of patients 7 to 10 days after cardiac
      surgery were significantly more likely to exhibit hemagglutination than the
      preoperative isolates (P = 0.015). By a quantitative adherence assay, we also
      observed that the hemagglutination titer and number of species of erythrocytes
      agglutinated correlated directly with adherence to polystyrene (P less than
      0.001). In addition, hemagglutinating isolates were significantly more likely to
      be recovered in high number from intravenous catheters when semiquantitative
      catheter culture techniques were used (P less than 0.001). We speculate that
      hemagglutinin(s) either plays a direct role in adherence to polymers and thus
      prosthetic-device infection or serves as an easily demonstrable marker for
      adherence-prone isolates.

PMID- 1398944
TI  - Leishmania donovani infection in scid mice: lack of tissue response and in vivo
      macrophage activation correlates with failure to trigger natural killer cell
      derived gamma interferon production in vitro.
AB  - Infection of immunocompetent mice with Leishmania donovani is characterized by
      the development of a tissue granulomatous response, in vivo macrophage
      activation, and a predominantly Th1-type CD4+ T-cell response. To determine
      whether a recently described T-cell-independent pathway of gamma interferon (IFN
      gamma) production involving the collaboration of macrophages and natural killer
      (NK) cells contributed to this pattern of events, we have investigated the
      responses of scid mice to L. donovani infection. The multiplication of parasites
      in the livers of scid mice progressed at a rate equivalent to that seen in BALB/c
      mice over the first 14 days of infection, but by day 28 scid mice had a fivefold
      higher parasite burden. This infection was not, however, accompanied by any
      demonstrable histological response in the liver or by elevated major
      histocompatibility complex class II expression on splenic macrophages. In vitro,
      L. donovani was unable to trigger IFN-gamma production from scid spleen cell
      cultures under conditions which allowed efficient triggering by bacterial
      stimuli. Although L. donovani also failed to stimulate the release of tumor
      necrosis factor, an important macrophage-derived cofactor for IFN-gamma secretion
      by NK cells, exogenous recombinant tumor necrosis factor alpha could not restore
      the IFN-gamma response. Even with the potent synergistic effect of exogenous
      interleukin-2, L. donovani was unable to stimulate this pathway to the same
      extent as Listeria monocytogenes. Indeed, L. donovani inhibited the response to
      L. monocytogenes in a dose-dependent fashion. Experiments involving the transfer
      of supernatants and the use of neutralizing monoclonal antibodies have failed to
      find evidence that interleukin-10 is involved in this inhibition. These data
      suggest that NK cell-derived IFN-gamma is unlikely to participate in the early
      regulation of visceral leishmaniasis in the mouse.

PMID- 1398946
TI  - A seroreactive 120-kilodalton beta-1,3-glucanase of Coccidioides immitis which
      may participate in spherule morphogenesis.
AB  - A beta-glucosidase of Coccidioides immitis was identified in electrophoresis gel
      separations of the concanavalin A-bound mycelial culture-filtrate-plus-lysate
      preparation. p-Nitrophenol-beta-D-glucopyranoside was used as the substrate to
      visualize the enzymatically active fraction in nonreducing gels. The gel
      isolated, chromatographically purified enzyme has an optimal pH of 8.0 and
      cleaves beta-1,3-glycosyl linkages. The alkaline beta-glucosidase was further
      characterized by a pI of 3.8 to 4.0, optimal activity at 37 to 40 degrees C, and
      molecular size of 120 kDa as identified by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis. The purified beta-glucosidase is identical to a previously
      reported 120-kDa antigen (Ag) which reacts with immunoglobulin M (IgM) tube
      precipitin (TP) antibody in sera from patients with coccidioidomycosis. The TP-Ag
      was described as a valuable serodiagnostic reagent for detection of specific IgM
      in patients with early coccidioidal infections. The beta-glucosidase, like the TP
      Ag, was localized in the cell wall and cytoplasmic vesicles of parasitic cells
      (spherules) by immunofluorescence and immunoelectron microscopy with specific
      antiserum raised against the purified enzyme. The boiled cell wall fraction
      isolated from these same young (presegmented) spherules was partially digested by
      the beta-glucosidase. Addition of a potent beta-glucosidase inhibitor, 1
      deoxynojirimycin, to the parasitic-phase culture medium at a concentration of 200
      microM blocked or retarded conversion of arthroconidia to spherules. Antibody was
      raised in guinea pigs against chromatographically purified 1-deoxynojirimycin
      which was conjugated with bovine serum albumin. The inhibitor was localized by
      immunofluorescence in the wall of the 1-deoxynojirimycin-treated cells. We
      suggest that the spherule wall-associated, alkaline hydrolase functions as a beta
      1,3-glucanase to provide for wall plasticity as well as intussusception of newly
      synthesized wall polymers during the period of rapid diametric growth of
      parasitic cells of C. immitis.

PMID- 1398945
TI  - Effect of growth temperature on outer membrane components and virulence of
      Aeromonas hydrophila strains of serotype O:34.
AB  - Growth of Aeromonas hydrophila strains from serotype O:34 at 20 and 37 degrees C
      in tryptic soy broth resulted in changes in the lipids, lipopolysaccharide (LPS),
      and virulence of the strains tested. Cells grown at 20 degrees C contained,
      relative to those cultured at 37 degrees C, increased levels of the phospholipid
      fatty acids hexadecanoate and octadecanoate and reduced levels of the
      corresponding saturated fatty acids. Furthermore, the lipid A fatty acids also
      showed thermoadaptation. In addition, LPS extracted from cells cultivated at 20
      degrees C was smooth, while the LPS extracted from the same cells cultivated at
      37 degrees C was rough. Finally, the strains were more virulent for fish and mice
      when they were grown at 20 degrees C than when they were grown at 37 degrees C
      and also showed increased different extracellular activities when they were grown
      at 20 degrees C.

PMID- 1398947
TI  - S-layer-mediated association of Aeromonas salmonicida with murine macrophages.
AB  - The interaction of Aeromonas salmonicida with the murine macrophage (M phi) cell
      line P388D1 was used as a convenient model to study the involvement of the
      bacterial crystalline surface array (or A-layer) in the association with M phi s.
      A-layer-positive (A+) cells readily associated with M phi s in phosphate-buffered
      saline, whereas A- mutants were unable to do so, even when the bacterium-M phi
      interaction was forced by centrifugation. M phi s selectively interacted with A+
      cells when challenged with mixtures of A+ and excess A- cells. Electron
      microscopy indicated that in phosphate-buffered saline only A+ bacteria were
      readily internalized, although by a nonconventional mechanism, suggesting that
      efficient phagocytosis in the absence of opsonins was A-layer mediated. Latex
      beads coated with a partially assembled A-layer were more efficiently taken up
      than uncoated or A-protein-coated beads, indicating that an organized A-layer was
      essential for M phi uptake. The reduced ability of M phi s plated on a substratum
      coated with the A-layer to bind A+ bacteria also suggested that association was
      both A-layer and receptor mediated. In the presence of tissue culture medium,
      competent M phi s interacted efficiently with A- bacteria and internalized them
      through conventional phagocytosis. A+ cells were markedly cytotoxic to M phi s,
      whereas the A-protein or A-layer was not. A- cells were cytotoxic to a lesser
      extent, suggesting that cytotoxicity was targeted.

PMID- 1398948
TI  - Lipid A in Helicobacter pylori.
AB  - Free lipid A of Helicobacter pylori was characterized with regard to chemical
      composition, reactivity with anti-lipid A antibodies, and activity in a Limulus
      lysate assay. The predominant fatty acids of H. pylori lipid A were 3-OH-18:0,
      18:0, 3-OH-16:0, 16:0, and 14:0. Hexosamine was present in amounts similar to
      those in Campylobacter jejuni or Salmonella typhimurium lipid A. The
      lipopolysaccharide of H. pylori contained 2-keto-3-deoxyoctonic acid, a common
      constituent of enterobacterial and C. jejuni lipopolysaccharides. In the enzyme
      linked immunosorbent assay, the doses of lipid A required to inhibit anti-lipid A
      by 50% (EI50 values) by absorption of the immune (rabbit) serum were 7.9, 1.2,
      and 1.4 micrograms of O-deacylated lipid A's from H. pylori, C. jejuni, and S.
      typhimurium per ml, respectively. The lower reactivity of H. pylori lipid A
      compared with those of the other two lipid A preparations (as shown by the higher
      EI50 value) was underscored by the use of a murine monoclonal anti-lipid A
      antibody in the inhibition assay. An EI50 value was not obtained at the
      concentrations tested for H. pylori lipid A; the corresponding figures for C.
      jejuni and S. typhimurium lipid A's were 13 and 14 micrograms/ml, respectively.
      No inhibition was obtained with H. pylori lipopolysaccharide, which showed a low
      molecular-weight profile on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The activity of H. pylori lipid A in the Limulus assay was
      approximately 71 and 650 times lower than those of C. jejuni and S. typhimurium
      lipid A's, respectively. These findings suggest that lipid A is an integral part
      of the outer cell wall of H. pylori. The lower reactivity of H. pylori lipid A
      with anti-lipid A antibodies and in the Limulus assay compared with that of C.
      jejuni or S. typhimurium lipid A may be explained by a different composition of
      the fatty acids, especially the 3-hydroxy fatty acids, and a possible deviating
      phosphorylation pattern.

PMID- 1398949
TI  - Recombinant interleukin-6 protects mice against experimental bacterial infection.
AB  - Because of reports of high levels of interleukin-6 (IL-6) in patients during
      infection, we studied the role of IL-6 in experimental infection. Mice infected
      with the facultative intracellular pathogen Listeria monocytogenes displayed high
      levels of IL-6 in their sera and tissues, particularly the spleen, 1 to 3 days
      after infection. At this time, the IL-6 titers correlated with bacterial numbers
      in individual mice and in groups of mice given graded doses of Listeria
      organisms. However, the presence of IL-6 in serum declined after 4 days, even
      when a large initial dose of bacteria meant that bacterial numbers were still
      increasing at this time. Recombinant mouse IL-6 injected intraperitoneally before
      infection protected mice in a dose-dependent manner. It was effective when given
      4 h before infection but not when administration was delayed for 24 h
      postinfection. It is therefore believed that IL-6 plays a role in early priming
      of the immune response to infection. Its exact function in this model is being
      investigated.

PMID- 1398950
TI  - Effects of gamma interferon and indomethacin in preventing Brucella abortus
      infections in mice.
AB  - Increased resistance to infection with Brucella abortus 2308 resulted when
      recombinant murine gamma interferon (rMuIFN-gamma) was given to mice both before
      and during infection but not when given only before infection. Mice given rMuIFN
      gamma had enhanced peritoneal and splenic macrophage bactericidal activity
      against B. abortus. Treatment of mice with rMuIFN-gamma plus indomethacin did not
      further enhance resistance to infection or macrophage bactericidal activity
      compared with that after treatment of mice with rMuIFN-gamma alone.

PMID- 1398951
TI  - Capacity of Mycobacterium avium isolates to grow well or poorly in murine
      macrophages resides in their ability to induce secretion of tumor necrosis
      factor.
AB  - The results of this study show that clinical isolates of Mycobacterium avium fall
      into two categories in terms of their capacity to grow within murine bone marrow
      derived macrophage cultures: those that grow progressively and those that are
      incapable of growing within such cells. Members of the first category were
      invariably of the smooth-transparent colonial type, while most of the second were
      of the smooth-doomed type. In addition, this paper shows that although all
      isolates induced tumor necrosis factor (TNF) secretion by host cells to some
      extent, this production was always delayed in isolates that subsequently grew
      well in the host cells. This observation, coupled with the demonstration that the
      growth of the latter isolates was inhibited by the exogenous addition of TNF,
      leads us to hypothesize that the ability of a given isolate to somehow avoid host
      macrophage TNF production early during the course of the infection is a key
      factor in the pathogenesis of the disease.

PMID- 1398952
TI  - Invasin expression in Yersinia pseudotuberculosis.
AB  - A 3.2-kb region on the chromosome of Yersinia pseudotuberculosis, called inv,
      encodes invasin, a 103-kDa protein of the bacterial outer membrane. Invasin
      mediates bacterial entry into cultured animal cells. Six Y. pseudotuberculosis
      strains isolated from animal or human infections were analyzed for the presence
      of inv-related sequences with a radiolabeled inv clone, pRI203. We found that inv
      specific sequences were present in all strains studied. Strains cured of
      virulence plasmid pYV were studied by Western immunoblot analysis with a
      monoclonal antibody directed against invasin. All but one strain produced
      invasin, but some strains produced more invasin than others. A strong correlation
      was found between the level of invasin production by these strains and their
      ability to enter into HEp-2 or CHO cells. The virulence of these strains was
      assessed in a murine model by measuring the number of bacteria in the spleen
      after intravenous challenge or in the mesenteric lymph nodes after intragastric
      challenge. The capacities of strains to invade cultured mammalian cells and to
      colonize the spleen were strongly correlative. In contrast, the ability of
      strains to translocate from the intestinal lumen to the mesenteric lymph nodes
      after intragastric inoculation did not correlate with their in vitro
      invasiveness.

PMID- 1398953
TI  - Depletion of tryptophan is not involved in expression of tryptophanyl-tRNA
      synthetase mediated by interferon.
AB  - Gamma interferon (IFN-gamma) affects tryptophan metabolism by mediating the
      expression of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA synthetase. In
      the present study, we investigated the role of indoleamine 2,3-dioxygenase
      mediated tryptophan depletion in the induction of tryptophanyl-tRNA synthetase by
      IFN-gamma. The addition of excess tryptophan to the culture medium did not affect
      the induction of tryptophanyl-tRNA synthetase by IFN-gamma, indicating that
      tryptophan degradation is not directly involved in the IFN-gamma-mediated
      expression of tryptophanyl-tRNA synthetase.

PMID- 1398954
TI  - Recombinant interleukin-1 alpha augments granuloma formation and cytokine
      production but not parasite clearance in mice infected with Leishmania donovani.
AB  - In vivo administration of various doses of recombinant interleukin-1 alpha to
      B10.D2/n mice chronically infected with Leishmania donovani resulted in enhanced
      formation of granulomas and in vitro production of gamma interferon. By direct
      microscopical enumeration, reduction in gross parasite burden in the viscera was
      not observed, however. These data highlight an important discordance between
      granuloma formation per se and parasite elimination and suggest that interleukin
      1 deficiency alone cannot account for the chronicity of this disease.

PMID- 1398955
TI  - Effect of gamma interferon on resolution of murine chlamydial genital infection.
AB  - Mice infected in the genital tract with the Chlamydia trachomatis agent of mouse
      pneumonitis were treated with monoclonal rat anti-gamma interferon (anti-IFN
      gamma) antibody to determine whether IFN-gamma participated in the resolution of
      the infection. In two experiments, anti-IFN-gamma antibody treatment resulted in
      significantly prolonged infections. In support of these data, passive
      administration of recombinant IFN-gamma to chronically infected nu/nu mice was
      able to bring about resolution of the infection in some animals.

PMID- 1398956
TI  - Safety and immunogenicity in North Americans of a single dose of live oral
      cholera vaccine CVD 103-HgR: results of a randomized, placebo-controlled, double
      blind crossover trial.
AB  - We conducted a double-blind, placebo-controlled, randomized crossover study to
      evaluate the safety and immunogenicity of a single 5 x 10(8)-CFU dose of live
      oral recombinant cholera vaccine CVD 103-HgR in 94 North American adults. The
      vaccine was well tolerated without associated adverse reactions. Despite minimal
      fecal excretion of vaccine, 97% of subjects exhibited serum vibriocidal antibody
      and 72% had antitoxin responses.

PMID- 1398957
TI  - Staining of surface antigens of Chlamydia trachomatis L2 in tissue culture.
AB  - Surface labeling of chlamydial elementary and reticulate bodies in L929 cells
      infected with Chlamydia trachomatis serotype L2 was monitored by using monoclonal
      antibodies (MAb) against the major outer membrane protein and lipopolysaccharide
      (LPS). Different staining and fixation procedures were used to detect these
      surface antigens during the developmental cycle. Anti-major outer membrane
      protein MAb yielded a clear staining pattern of exclusively chlamydial inclusions
      independent of the fixation or staining technique used. Anti-LPS MAb gave a faint
      staining pattern of reticulate bodies when methanol fixation was used and showed
      that LPS was released from chlamydiae into the host cell cytoplasm and into the
      surroundings of the infected host cell. However, when paraformaldehyde
      glutardialdehyde fixation was used, extracellular LPS staining was not observed.
      The data show that chlamydial LPS is loosely bound in the bacterial outer
      membrane but suggest that shedding of LPS is a fixation artifact.

PMID- 1398958
TI  - Effect of exogenous sialylation of the lipooligosaccharide of Neisseria
      gonorrhoeae on opsonophagocytosis.
AB  - Serum-sensitive Neisseria gonorrhoeae strains become serum resistant when grown
      in the presence of a sialic acid precursor, cytidine monophospho-N
      acetylneuraminic acid. We examined the abilities of human neutrophils to
      phagocytose sialylated and nonsialylated gonococci and observed a decrease in the
      complement-dependent phagocytosis of sialylated gonococci compared with that of
      nonsialylated gonococci (50.7 versus 25.9% survival at 30 min). This decrease in
      opsonophagocytosis after sialylation may contribute to the pathogenicity of
      gonococcal infections.

PMID- 1398959
TI  - Mycobacterium leprae produces extracellular homologs of the antigen 85 complex.
AB  - The antigen 85 complex is a set of at least three closely related secreted
      proteins (85A, 85B, and 85C) of 30 to 32 kDa produced by Mycobacterium
      tuberculosis and other mycobacteria. Their prominence in Mycobacterium leprae,
      the one obligate intracellular pathogen of the genus, had been assumed on the
      basis of immunological evidence and proof of the existence of the gene encoding
      the 85B protein of the complex. We have now observed the production of this
      family of proteins by M. leprae through analysis of various fractions by Western
      blotting (immunoblotting) with monospecific rabbit antisera raised against the
      individual Mycobacterium bovis BCG 85A, 85B, and 85C proteins. A predominant
      cross-reactive band with an apparent molecular mass of 30 kDa was detected in
      extracts of nondisrupted whole M. leprae and in soluble fractions prepared from
      the tissues of M. leprae-infected armadillos. Further studies of the subcellular
      distribution of this protein within the bacterium confirmed that it is secreted
      by the organism, an observation that explains past difficulties in detecting the
      antigen 85 complex in M. leprae. Confirmation that the M. leprae product is a
      member of the antigen 85 complex was obtained by comparison of peptide
      fingerprints with those from the BCG product. The pattern of reactivity of the M.
      leprae antigen 85 complex with anti-M. bovis BCG 85B serum, as well as two
      dimensional electrophoresis, established that the 85B component was the
      predominant member of the complex in M. leprae. The fibronectin-binding capacity
      of the M. leprae and BCG 85 complexes was reinvestigated by new approaches and is
      questioned. Nevertheless, the results obtained with the native proteins reinforce
      previous reports, derived primarily from the use of homologous proteins, that the
      antigen 85 complex is one of the dominant protein immunogens of the leprosy
      bacillus.

PMID- 1398960
TI  - Role of crl in avian pathogenic Escherichia coli: a knockout mutation of crl does
      not affect hemagglutination activity, fibronectin binding, or Curli production.
AB  - This study determined the role of crl in the production of curli by, the
      hemagglutination activity of, and fibronectin binding by avian pathogenic
      Escherichia coli chi 7122. Curli, an extracellular structure that binds
      fibronectin, was recently described (A. Olsen, A. Jonsson, and S. Normark, Nature
      [London] 338:652-655, 1989). The crl gene product was hypothesized to be the
      subunit monomer of curli and to bind fibronectin. E. coli HB101, which does not
      contain crl, binds fibronectin and produces curli when harboring a plasmid
      containing the crl gene. We show that HB101 hemagglutinates chicken erythrocytes
      when harboring the crl gene and that chi 7122 hemagglutinates chicken
      erythrocytes, binds fibronectin, and produces curli. Hemagglutination activity,
      fibronectin binding, and curli production are best expressed by chi 7122 and
      HB101 harboring the crl gene when the bacteria are grown on colonization factor
      antigen agar at 26 degrees C. The expression of hemagglutination activity,
      fibronectin binding, and curli production by both strains is decreased by growth
      on this agar at an increased temperature, of an increased osmolarity, or in an
      anaerobic atmosphere. This results indicates that the crl gene plays a role in
      the expression of the three phenotypes in HB101 and possibly in chi 7122 as well.
      We inactivated crl in chi 7122 by allele replacement in the expectation of
      abolishing hemagglutination activity, fibronectin binding, and curli production.
      The mutation was verified by Southern blot analysis and by a polymerase chain
      reaction, and there was no evidence of a second crl gene in chi 7122. However,
      the mutant of chi 7122 lacking crl hemagglutinated chicken erythrocytes, bound
      fibronectin, and produced curli at wild-type levels. This result indicates that
      crl plays a nonessential role in the expression of these three phenotypes in chi
      7122.

PMID- 1398961
TI  - Some properties of purified Escherichia coli heat-stable enterotoxin II.
AB  - We examined the biological properties of purified Escherichia coli heat-stable
      enterotoxin II (STII) using mouse intestinal loop assays and compared these
      properties with those of heat-stable enterotoxin I (STI) and cholera toxin (CT).
      The action of STII over time differed from those of STI and CT. STII did not
      alter cyclic GMP or cyclic AMP levels in intestinal mucosal cells. Our results
      supported the idea that the mechanism of action of STII in inducing fluid
      secretion is different from the mechanisms of action of STI and CT. This
      hypothesis was further supported by the fact that an anti-STII neutralizing serum
      did not neutralize the activities of STI and CT. Subsequently, we examined the
      involvement of prostaglandins in the action of STII. The level of prostaglandin
      E2 in the fluid accumulated as a result of the action of STII increased, and the
      prostaglandin synthesis inhibitors aspirin and indomethacin significantly reduced
      the response to STII. These results implicate prostaglandin E2 in the mechanism
      of action of STII.

PMID- 1398962
TI  - A novel neutrophil-activating factor released by Trichomonas vaginalis.
AB  - We have investigated the effects of a novel neutrophil-activating factor released
      by Trichomonas vaginalis (TV-NAF) on neutrophil chemotaxis. TV-NAF was present in
      the supernatant from 10(7) T. vaginalis (STV) cultured in 1 ml of serum-free
      Hanks' balanced salt solution (HBSS) at 37 degrees C for 30 min. With a
      multichamber chemotactic assay, we found that there were 112 +/- 15 migrated
      neutrophils (mean +/- standard deviation, n = 7) for STV and 11 +/- 4 for HBSS
      per high-power field (x 400). STV was also able to induce neutrophil actin
      assembly (increased 1.5-fold), enhance expression of complement receptor type 3
      (increased 5-fold), and promote intracellular calcium mobilization (increased 2.5
      fold). There was no chemotactic activity in the preparation of STV from killed
      trichomonads. The fact that heating up to 100 degrees C or deproteinization by
      treatment with proteinase K at 65 degrees C for 1 h did not abolish its
      chemotactic activity suggests that the TV-NAF involved was not a protein. The
      chemotactic activity of TV-NAF was associated with the fraction containing small
      molecules of less than 3,000 Da. Therefore, the possibility that eicosanoid
      production by trichomonads is responsible for neutrophil activation was
      investigated. Leukotriene B4 (LTB4; 500 pg/ml) but not thromboxane B2 (< 20
      pg/ml) or prostaglandin E2 (< 8 pg/ml) was found in the STV by radioimmunoassay.
      Production of LTB4 by trichomonads was time dependent and increased twofold when
      arachidonic acid (100 microM) was added but was not decreased when eicosanoid
      inhibitors were present. Evidence for the presence of LTB4 in STV was further
      provided by the fact that rabbit anti-LTB4 antiserum could abolish the
      chemotactic activity of STV. These studies suggest that the spontaneous release
      of TV-NAF, which is most likely LTB4, may activate neutrophils, presumably
      through a different arachidonate metabolic pathway than that in mammalian cells.

PMID- 1398963
TI  - Identification of proteases from periodontopathogenic bacteria as activators of
      latent human neutrophil and fibroblast-type interstitial collagenases.
AB  - Activation of latent human fibroblast-type and neutrophil interstitial
      procollagenases as well as degradation of native type I collagen by supra- and
      subgingival dental plaque extracts, an 80-kDa trypsinlike protease from
      Porphyromas gingivalis (ATCC 33277), a 95-kDa chymotrypsinlike protease from
      Treponema denticola (ATCC 29522), and selected bacterial species commonly
      isolated in periodontitis was studied. The bacteria included were Prevotella
      intermedia (ATCC 25261), Prevotella buccae (ES 57), Prevotella oris (ATCC 33573),
      Porphyromonas endodontalis (ES 54b), Actinobacillus actinomycetemcomitans (ATCC
      295222), Fusobacterium nucleatum (ATCC 10953), Mitsuokella dentalis (DSM 3688),
      and Streptococcus mitis (ATCC 15909). None of the bacteria activated latent
      procollagenases; however, both sub- and supragingival dental plaque extracts
      (neutral salt extraction) and proteases isolated from cell extracts from
      potentially periodontopathogenic bacteria P. gingivalis and T. denticola were
      found to activate latent human fibroblast-type and neutrophil interstitial
      procollagenases. The fibroblast-type interstitial collagenase was more
      efficiently activated by bacterial proteases than the neutrophil counterpart,
      which instead preferred nonproteolytic activation by the oxidative agent
      hypochlorous acid. The proteases were not able to convert collagenase tissue
      inhibitor of metalloproteinase (TIMP-1) complexes into active form or to change
      the ability of TIMP-1 to inhibit interstitial collagenase. None of the studied
      bacteria, proteases from P. gingivalis and T. denticola, or extracts of supra-
      and subgingival dental plaque showed any significant collagenolytic activity.
      However, the proteases degraded native and denatured collagen fragments after
      cleavage by interstitial collagenase and gelatinase. Our results indicate that
      proteases from periodontopathogenic bacteria can act as direct proteolytic
      activators of human procollagenases and degrade collagen fragments. Thus, in
      concert with host enzymes the bacterial proteases may participate in periodontal
      tissue destruction.

PMID- 1398964
TI  - Identification of 2,3-dihydroxybenzoic acid as a Brucella abortus siderophore.
AB  - Brucella abortus grown in low-iron medium or in the presence of iron chelators
      [ethylenediamine-di(o-hydroxyphenylacetic acid) and 2,2-dipyridyl] showed reduced
      cell yields and released a material positive in chemical and biological assays
      for catechols. This material was purified from culture fluids of B. abortus 2308
      by chromatography on agarose-iminodiacetic acid-Fe3+ and identified as 2,3
      dihydroxybenzoic acid (2,3-DHBA) by thin-layer chromatography, paper
      electrophoresis, and UV-visible nuclear magnetic resonance and mass spectroscopy.
      No other major catechols were observed at different stages of growth, and 2,3
      DHBA was also produced upon iron limitation by representative strains of B.
      abortus biotypes 1, 5, 6, and 9. Both synthetic 2,3-DHBA and the natural catechol
      relieved the growth inhibition of B. abortus 2308 by ethylenediamine-di(o
      hydroxyphenylacetic acid), and 2,3-DHBA promoted 55Fe uptake by B. abortus 2308
      by an energy-dependent mechanism. Two other monocatechols tested, 2,3
      dihydroxybenzoyl-Ser and 2,3-dihydroxybenzoyl-Gly, also promoted 55Fe uptake.
      More complex catechol siderophores (agrobactin and enterobactin), hydroxamate
      siderophores (aerobactin, ferrichrome, and deferriferrioxamine mesylate
      [Desferal]), and an EDTA-related siderophore (rhizobactin) failed to mediate 55Fe
      uptake. B. abortus cells grown in low-iron medium or in medium with iron had
      similar rates of iron uptake when supplied with 55Fe-2,3-DHBA, and the release of
      2,3-DHBA under iron starvation was not associated with the expression of new
      outer membrane proteins. These results suggest an uptake system in which only the
      synthesis of the siderophore is regulated by the iron available for growth.

PMID- 1398965
TI  - Antibodies to meningococcal class 1 outer membrane proteins in South African
      complement-deficient and complement-sufficient subjects.
AB  - Inhibition assays were used to investigate human serum antibodies to the
      meningococcal class 1 outer membrane proteins. We adapted the whole-cell enzyme
      linked immunosorbent assay technique to determine the ability of sera to inhibit
      the binding of murine subtyping monoclonal antibodies. Serum samples from 33
      South African subjects with a deficiency in the sixth component of complement as
      well as serum samples from various groups of complement-sufficient subjects were
      investigated. Subjects were subdivided according to whether they were (i)
      convalescent from Neisseria meningitidis infections, (ii) nonconvalescent, or
      (iii) controls. Preliminary subtyping investigations had shown that P1.2 was
      present on 36% of meningococcal clinical isolates from Cape Province, South
      Africa. Assays with the anti-P1.2 antibodies showed the presence of high antibody
      levels in many deficient sera and moderately elevated levels in some sera from
      the complement-sufficient convalescent patients. P1.2, P1.4, P1.15, and P1.16 are
      epitopes situated on loop 4 of the class 1 outer membrane proteins, whereas P1.7
      is on loop 1. Inhibition assays showed that human sera that inhibited binding by
      P1.2 monoclonal antibodies tended to inhibit the other monoclonal antibodies
      directed to loop 4 epitopes. This suggests that the epitopes recognized by the
      human antibodies are not exactly the same as the epitopes recognized by the
      murine monoclonal antibodies and raises the possibility of the importance of
      other epitopes.

PMID- 1398967
TI  - Influence of serotype of group B streptococci on C3 degradation.
AB  - Serotype III strains of group B streptococci (GBS) are isolated from the majority
      of young infants with bacteremia or meningitis. We hypothesized that serotype
      associated differences in structure of the type-specific capsular polysaccharide
      or the presence of c protein would influence the extent to which C3 degradation
      occurs on GBS and that type-specific antibody would alter C3 deposition or
      degradation patterns. When clinical isolates of GBS representing serotypes Ia,
      Ib/c, II (with or without c protein) and III were employed with
      hypogammaglobulinemic serum as an opsonic source, a remarkable similarity was
      observed in patterns of C3 deposition and degradation for each of the four GBS
      serotypes and between strains with or without c protein. Both C3b and iC3b were
      detected by 5 min and throughout a 90-min opsonization interval. Less deposition
      occurred at 5 min on serotypes Ia and Ib/c than on types II and III GBS. Minimal
      degradation to C3d or smaller fragments was observed. Type-specific antibody
      facilitated C3b deposition on GBS and C3b degradation to iC3b early in
      opsonization. Possibly, accessibility of C3 fragments to neutrophil receptors,
      rather than the extent to which the surface permits C3 degradation, accounts for
      differential virulence among GBS serotypes.

PMID- 1398966
TI  - Protective murine monoclonal antibodies to Cryptococcus neoformans.
AB  - Several murine monoclonal antibodies (MAbs) specific for the capsular
      glucuronoxylomannan of Cryptococcus neoformans were studied for their capacity to
      confer protection when passively administered to lethally infected mice. The MAb
      group studied recognized at least three distinct epitopes and included
      immunoglobulin M (IgM), IgG3, IgG1, and IgA isotypes. The protection model used
      A/J and BALB/c mice infected intraperitoneally with 10(8) cryptococci. The MAbs
      were administered either immediately preceding or, in one experiment, 24 to 48 h
      prior to infection. Protective efficacy was assessed by the ability of passively
      administered MAbs to prolong the survival of lethally infected mice. Three IgM
      MAbs, each of which recognized a distinct epitope, were able to prolong survival
      of lethally infected mice to different extents. A set of IgM, IgG3, IgG1 and IgA
      MAbs which utilize the same immunoglobulin gene elements and were derived from
      the same B-cell clone exhibited significant class differences in protective
      efficacy with IgA, IgG1 > IgM > IgG3. The results confirm that protective MAbs
      against C. neoformans capsular polysaccharide exist and strongly suggest that
      both epitope specificity and isotype are important determinants of protective
      efficacy.

PMID- 1398968
TI  - Proliferative responses and gamma interferon and tumor necrosis factor production
      by lymphocytes isolated from tracheobroncheal lymph nodes and spleen of mice
      aerosol infected with Bordetella pertussis.
AB  - A group of mice was aerosol infected with live, virulent Bordetella pertussis
      bacteria. During a period of 7 weeks following the infection, with intervals of 1
      week, lymphocytes were isolated from the tracheobroncheal lymph nodes (TBL) and
      the spleens (SPL) of the infected mice. The in vitro proliferative responses as
      well as the gamma interferon and tumor necrosis factor production levels of the
      isolated lymphocytes in response to stimulation with whole killed B. pertussis
      bacteria were measured as parameters for cell-mediated immunity (CMI). The course
      of the infection was monitored by counting of CFU in the lungs of the mice.
      Moreover, antibody responses in serum against a range of B. pertussis antigens
      were assessed. The results showed that a vigorous proliferative response of the
      TBL and SPL to stimulation with whole killed B. pertussis bacteria was induced by
      the infection. The proliferative response of the TBL was significantly higher
      than the response of the SPL. The proliferative responses were maximal 3 to 4
      weeks after the infection and were paralleled by in vitro gamma interferon and
      tumor necrosis factor production upon specific stimulation. The development of
      the CMI was observed simultaneously with the clearance of the infection from the
      lungs. Antibody responses became measurable in the sera only after the infection
      was cleared. A specific CMI against pertussis toxin, the filamentous
      hemagglutinin, the 69-kDa outer membrane protein, and the agglutinogens 2 and 3,
      antigens which are under consideration for inclusion in future acellular
      pertussis vaccines, was successfully demonstrated in mice 3 weeks after the
      infection.

PMID- 1398969
TI  - Rapid generation of specific protective immunity to Francisella tularensis.
AB  - Mice inoculated either subcutaneously (s.c.) or intradermally (i.d.) with a
      sublethal dose of Francisella tularensis LVS are immune to a lethal
      intraperitoneal (i.p.) or intravenous (i.v.) challenge of LVS. Here, we show that
      this immunity developed quite rapidly: mice given a sublethal dose of live LVS
      s.c. or i.d. (but not i.v.) withstood lethal i.p., i.v., or i.d. challenge as
      early as 2 days after the initial inoculation, despite the presence of bacterial
      burdens already in tissues. The magnitude of this early protection was quite
      impressive. The i.p. 50% lethal dose (LD50) in naive C3H/HeN mice was only 2
      bacteria, while the i.p. LD50 in mice given 10(4) LVS i.d. 3 days previously was
      3 x 10(6) bacteria. Similarly, the i.v. LD50 in C3H/HeN mice shifted from 3 x
      10(2) in naive mice to 5 x 10(6) in primed mice within 3 days after i.d. LVS
      infection. Comparable changes in the i.p. and i.v. LD50 were observed in C57BL/6J
      mice. This rapid generation of protective immunity was specific for LVS, in that
      mice given a sublethal i.d. inoculation of LVS did not survive a lethal challenge
      with either Salmonella typhimurium W118 or Escherichia coli O118 BORT at any
      time, nor could mice given sublethal doses of S. typhimurium, E. coli, or
      Mycobacterium bovis BCG survive lethal doses of LVS. Although an increase in the
      mean time to death from S. typhimurium infection was noted when mice were given a
      sublethal i.d. dose of LVS 4 to 14 days earlier, no overall increase in
      protection or change in the S. typhimurium LD50 was observed. Thus, sublethal
      infection with LVS at skin sites induced rapid and specific protective immunity.

PMID- 1398971
TI  - Molecular characterization of a genomic region associated with virulence in
      Dichelobacter nodosus.
AB  - The major pathogen implicated in footrot, a highly contagious disease of sheep,
      is the strict anaerobe Dichelobacter nodosus (formerly Bacteroides nodosus).
      Sequence analysis of a 2,262-bp segment of the D. nodosus genome which is more
      prevalent in virulent isolates than in other isolates showed the presence of four
      open reading frames which appeared to have consensus transcriptional and
      translational start signals. These virulence-associated genes have been
      designated vapABCD. Two of the three copies of the vap region in the genome of
      the reference strain D. nodosus A198 were shown to carry all of the vap genes,
      whereas one copy contained only the vapD gene. The VapD protein was gel purified,
      shown to contain the predicted amino-terminal sequence, and used to raise rabbit
      antibodies. Western blots (immunoblots) showed that all of the D. nodosus strains
      tested that contained the vap region produced the VapD protein. The VapD protein
      had significant amino acid sequence identity with open reading frame 5 from the
      cryptic plasmid of Neisseria gonorrhoeae, and the vapBC operon had sequence
      similarity with the trbH region of the Escherichia coli F plasmid. It is proposed
      that these gene regions evolved from the integration of a conjugative plasmid
      from another bacterial species into the D. nodosus chromosome.

PMID- 1398970
TI  - Uptake and intracellular survival of Bordetella pertussis in human macrophages.
AB  - Recent reports have demonstrated that Bordetella pertussis has invasive behavior
      in vivo and in vitro. In this study, we investigated the ability of a virulent
      strain, avirulent mutants, and mutants deficient in specific virulence factors to
      enter and survive intracellularly in human macrophages in vitro. Uptake of
      virulent B. pertussis was dose dependent and occurred in the absence of serum or
      specific antibody, with entry occurring via a microfilament-dependent phagocytic
      process. The virulent wild-type parental strain was internalized and persisted
      intracellularly over the 3 days of experiments, as determined by transmission
      electron microscopy and by recovery of viable plate counts. This is the first
      report of long-term survival of B. pertussis in human macrophages. Avirulent
      mutants entered macrophages, but at only an average of 1.5% of virulent parental
      levels, and did not survive intracellularly. Mutants which did not express
      adenylate cyclase toxin, filamentous hemagglutinin, or pertussis toxin had
      decreased abilities to enter and to survive inside macrophages. The results
      suggest that the internalization process, as well as intracellular survival, is
      virulence dependent and that mutations which inactivate expression of virulence
      factors may affect both. The ability of B. pertussis to enter and persist inside
      macrophages may be important not only for survival of the bacteria but also in
      the pathogenesis of whooping cough.

PMID- 1398972
TI  - Colony-stimulating factors activate human macrophages to inhibit intracellular
      growth of Histoplasma capsulatum yeasts.
AB  - Recombinant cytokines and colony-stimulating factors (CSFs) were tested for their
      abilities to activate human monocytes/macrophages (M phi) to inhibit the
      intracellular growth of or kill Histoplasma capsulatum yeasts. None of the
      cytokines or CSFs or combinations of cytokines and CSFs activated M phi
      fungistatic activity when they were added to M phi monolayers concurrently with
      yeasts. In contrast, culture of monocytes for 7 days in the presence of
      interleukin 3, granulocyte-M phi CSF, or M phi CSF stimulated M phi fungistatic
      (but not fungicidal) activity against H. capsulatum yeasts in a concentration
      dependent manner. Optimal activation of M phi by CSFs required 5 days of
      coculture, and the cultures had to be initiated with freshly isolated peripheral
      blood monocytes. Culture of monocytes with combinations of CSFs or addition of
      CSFs during the 24 h of coculture with the yeasts did not further enhance M phi
      fungistatic activity for H. capsulatum. Addition of gamma interferon or tumor
      necrosis factor alpha to CSF-activated M phi also did not enhance M phi
      fungistatic activity. These results suggest that interleukin 3, granulocyte-M phi
      CSF, and M phi CSF may play a role in the cell-mediated immune response to H.
      capsulatum by enhancing monocyte/M phi fungistatic activity.

PMID- 1398973
TI  - Identification of Chlamydia trachomatis antigens by use of murine T-cell lines.
AB  - Chlamydia-specific short-term T-cell lines were used in conjunction with
      immunoblot techniques to examine Chlamydia trachomatis proteins for T-cell
      stimulatory activity. This study was undertaken because of the known role of T
      cells in the resolution and pathogenesis of chlamydial infections. Therefore,
      determination of which chlamydial proteins are T-cell antigens and whether they
      evoke protective immunity or contribute to immunopathology is crucial. Immune
      lymph node cells were stimulated with whole chlamydial organism (elementary body)
      to derive predominantly CD4+ T-cell lines. Proteins from the elementary body and
      the outer membrane and cloned proteins were examined for antigenicity with these
      T-cell lines in a proliferation assay. Although a majority of the elementary body
      protein fractions were positive in this assay, only four of the outer membrane
      fractions were stimulatory. The cloned major outer membrane protein and outer
      membrane protein 2 were stimulatory in the assay and may account for the
      reactivity in three of the four positive outer membrane fractions. The C.
      trachomatis heat shock protein 60, examined because of its putative role in
      causing delayed-type hypersensitivity, was found to stimulate the CD4+ T cells.
      This approach with short-term T-cell lines with polyclonal reactivity was
      sensitive and specific in identifying chlamydial proteins as T-cell antigens.

PMID- 1398975
TI  - Interaction of the fish pathogen Aeromonas salmonicida with rainbow trout
      macrophages.
AB  - A procedure was developed to culture rainbow trout macrophages (M phi) on
      supported glass coverslips. Using this method and a variety of well-characterized
      Aeromonas salmonicida strains with normal or altered cell surfaces, we
      investigated the role of this unusual bacterial surface in the bacterium-M phi
      interaction. An intact crystalline protein array, the A-layer, mediated adherence
      of A. salmonicida cells to M phi even in the absence of opsonins. In contrast,
      unopsonized cells of an A-layer-negative (A-) mutant with a smooth
      lipopolysaccharide (LPS) layer were unable to interact with M phi. However, this
      ability was recovered when the A-layer was reconstituted onto the smooth LPS
      surface of these A- LPS+ cells. Two A. salmonicida mutants possessing the A-layer
      in different disorganized states had a reduced ability to interact with M phi. A+
      cells grown under calcium limitation produced A-layers locked into an alternative
      conformation which mediated the highest levels of M phi association in the
      absence of opsonins or any other surface coating. Coating A+ cells with hemin
      greatly increased their levels of M phi association, and bacterial cells grown on
      trout blood agar plates also had a dramatic increase in their ability to interact
      with M phi. Only A+ A. salmonicida cells were highly cytotoxic to trout M phi,
      especially after being coated with hemin, presumably due to a more focused
      targeting of the bacterial cell onto the M phi surface and/or into the
      intracellular regions of the M phi.

PMID- 1398974
TI  - Lactoferrin release and interleukin-1, interleukin-6, and tumor necrosis factor
      production by human polymorphonuclear cells stimulated by various
      lipopolysaccharides: relationship to growth inhibition of Candida albicans.
AB  - Lipopolysaccharides (LPSs) from Escherichia coli, Serratia marcescens, and
      Salmonella typhimurium, at doses from 1 to 100 ng/ml, strongly enhanced growth
      inhibition of Candida albicans by human polymorphonuclear leukocytes (PMN) in
      vitro. Flow cytometry analysis demonstrated that LPS markedly augmented
      phagocytosis of Candida cells by increasing the number of yeasts ingested per
      neutrophil as well as the number of neutrophils capable of ingesting fungal
      cells. LPS activation caused augmented release of lactoferrin, an iron-binding
      protein which itself could inhibit the growth of C. albicans in vitro. Antibodies
      against lactoferrin effectively and specifically reduced the anti-C. albicans
      activity of both LPS-stimulated and unstimulated PMN. Northern (RNA blot)
      analysis showed enhanced production of mRNAs for interleukin-1 beta, tumor
      necrosis factor alpha, and interleukin-6 and in neutrophils within 1 h of
      stimulation with LPS. The cytokines were also detected in the supernatant of the
      activated PMN, and their synthesis was prevented by pretreatment of LPS
      stimulated PMN with protein synthesis inhibitors, such as emetine and
      cycloheximide. These inhibitors, however, did not block either lactoferrin
      release or the anti-Candida activity of LPS-stimulated PMN. These results
      demonstrate the ability of various bacterial LPSs to augment neutrophil function
      against C. albicans and suggest that the release of a candidastatic, iron-binding
      protein, lactoferrin, may contribute to the antifungal effect of PMN. Moreover,
      the ability to produce cytokines upon stimulation by ubiquitous microbial
      products such as the endotoxins points to an extraphagocytic, immunomodulatory
      role of PMN during infection.

PMID- 1398977
TI  - Characterization of a toxin A-negative, toxin B-positive strain of Clostridium
      difficile.
AB  - This study was undertaken to examine toxin production by Clostridium difficile
      8864, a naturally occurring isolate that has been reported to produce toxin B in
      the absence of toxin A. To date, this is the only strain of C. difficile reported
      to produce only one of the toxins. The results of our initial studies with
      antibodies against toxins A and B confirmed these observations. Toxin B from
      strain 8864 and from VPI strain 10463, a strain that produces high levels of both
      toxin A and toxin B, was purified to homogeneity by sequential anion-exchange
      chromatography on DEAE-Sepharose CL-6B, gel filtration on Ultrogel AcA22, and
      immunoadsorption chromatography, and their toxic activities were compared. Our
      results showed that toxin B from strain 8864 and toxin B from C. difficile VPI
      strain 10463 were comparable in their cytotoxic activities and that the 8864
      toxin B was more lethal. In addition, we observed that toxin B from strain 8864
      was weakly enterotoxic, which may explain the ability of this strain to cause
      intestinal disease in hamsters treated with antibiotics. Analysis with specific
      antibodies showed that the toxin B molecules from these strains were highly
      related but contained distinct epitopes. The results of hybridization studies
      with probes specific for the toxin B gene of VPI strain 10463 demonstrated
      differences between the toxin B genes of the two strains. In addition, probes
      specific for the toxin A gene of VPI strain 10463 showed that strain 8864
      contains a region which shows identity with the 5' end of the toxin A gene but
      not the region of the gene which encodes a hydrophobic region and the repeating
      units.

PMID- 1398976
TI  - Characterization of the Streptococcus mutans GS-5 fruA gene encoding exo-beta-D
      fructosidase.
AB  - The complete nucleotide sequence (5,010 bp) of the fructanase gene (fruA) and
      flanking regions of the chromosome of Streptococcus mutans GS-5 was determined.
      The fruA gene appears to be the sole transcript arising from a proximal promoter.
      The presumed precursor of the secreted FruA protein consists of 1,423 amino
      acids, and it has an M(r) of 158,656 and a pI of 4.82. The N terminus of FruA has
      characteristics in common with signal peptides of gram-positive organisms. The C
      terminus consists of a serine- and threonine-rich region, followed by the peptide
      LPDTGD, 4 charged amino acids, 21 amino acids with a strongly hydrophobic
      character, and a charged pentapeptide tail, which are proposed to correspond to
      the wall-spanning region, the LPXTGX consensus sequence, and the membrane
      spanning domains of surface-associated proteins of gram-positive cocci. The FruA
      protein has significant homology with the Bacillus subtilis levanase (SacC), the
      Bacteroides fragilis levanase (ScrL), yeast invertases, and a number of other
      beta-fructosidases but not with fructosyltransferase, glucosyltransferases, or
      glucan-binding proteins of oral streptococci. Genes with homology to fruA were
      detected in S. mutans serotype c, e, and f strains, Streptococcus rattus,
      Streptococcus salivarius, and Streptococcus sanguis. A deletion derivative of
      FruA lacking the C-terminal 437 amino acids was still functional and could
      hydrolyze beta-(2,6)- and beta-(2,1)-linked sugars, but with altered preference
      for substrates. The data begin to define functional domains of the FruA protein
      and potential regulatory sites for induction, repression, growth rate control,
      and posttranslational localization of this multifunctional enzyme.

PMID- 1398978
TI  - Visualizations of binding and internalization of two nonlinked protein components
      of botulinum C2 toxin in tissue culture cells.
AB  - Binding and internalization of two nonlinked components of botulinum C2 toxin
      were visualized in tissue culture cells with components directly labeled with
      fluorescence. The binding of both untrypsinized and trypsinized component II (UT
      II and T-II, respectively) to common specific sites on the cell membrane was
      evidenced by competitive binding between fluorescence-labeled and unlabeled
      components. The distribution patterns of fluorescence-labeled T-II and UT-II
      after binding to cells at 37 degrees C were different; T-II clustered on the cell
      membrane and entered the cells in endosomes, whereas UT-II entered the cells
      inefficiently and not in vesicles and was distributed on the nuclear surface. The
      difference may be due to the multivalent property of T-II, which is not shared
      with UT-II. Fluorescence-labeled component I, which binds only to cells bound
      with T-II, entered cells by the same route as T-II did; both colocated on the
      same clusters on the cell membrane and also in the same vesicles in the
      cytoplasm. The present results suggest that component I of C2 toxin, which ADP
      ribosylates cytoplasmic actin, directly binds to T-II but not to UT-II on the
      cell membrane and is internalized into cells together with T-II in the same
      endosomes.

PMID- 1398979
TI  - Transfer of a dense granule protein of Plasmodium falciparum to the membrane of
      ring stages and isolation of dense granules.
AB  - A 14-kDa protein was localized to the dense granules of Plasmodium falciparum by
      immunoelectron microscopy with monoclonal antibody 1H1. The protein was present
      in dense granules in late-stage schizonts and free merozoites. After invasion,
      the protein was localized exclusively on the membrane of the newly invaded ring.
      The protein is referred to as RIMA, for ring membrane antigen. The 14-kDa protein
      was synthesized late in schizogony as determined by immunofluorescence microscopy
      and immunoblotting. At the late schizont stage it was distributed diffusely
      throughout the intracellular schizont. Only at the segmenter stage was the
      protein localized in defined spots that correspond to dense granules. Dense
      granules were isolated from schizont-infected erythrocytes by subcellular
      fractionation on a sucrose gradient. Fractions containing the 14-kDa protein were
      detected by immunoblotting with monoclonal antibody 1H1. The 14-kDa protein was
      first detected in vesicles at the late (8-nucleus) schizont stage. Mature dense
      granules sedimented with a peak density of 1.17 g/ml, which is similar to the
      density of rhoptries isolated by the same procedure.

PMID- 1398981
TI  - The major anaerobically induced outer membrane protein of Neisseria gonorrhoeae,
      Pan 1, is a lipoprotein.
AB  - Pan 1 is an acidic outer membrane protein of Neisseria gonorrhoeae that is
      expressed only when gonococci are grown anaerobically. On silver-stained sodium
      dodecyl sulfate-polyacrylamide gels, Pan 1 migrates as an intense but diffuse 54
      kDa protein. The deduced amino acid sequence of Pan 1 from the aniA
      (anaerobically induced protein) open reading frame reveals a lipoprotein
      consensus sequence, Ala-Leu-Ala-Ala-Cys, and a processed molecular mass of 39
      kDa. Furthermore, there is strong homology at the N terminus and C terminus of
      Pan 1 to the termini of the gonococcal outer membrane lipoproteins Lip and Laz.
      [3H]palmitic acid labeling of gonococci grown under oxygen-limited conditions
      demonstrated specific incorporation of label into Pan 1, suggesting further that
      Pan 1 is a lipoprotein.

PMID- 1398980
TI  - Low-passage-associated proteins of Borrelia burgdorferi B31: characterization and
      molecular cloning of OspD, a surface-exposed, plasmid-encoded lipoprotein.
AB  - Borrelia burgdorferi, the causative agent of Lyme disease, loses its ability to
      infect and cause disease in mammalian hosts after repeated in vitro passage. To
      identify proteins preferentially expressed by the low-passage strain and thus
      representing potential virulence factors, the polypeptide profiles of virulent,
      low-passage and nonvirulent, high-passage forms of B. burgdorferi B31 were
      compared by nonequilibrium pH gradient two-dimensional gel electrophoresis. Four
      low-passage-associated proteins with relative molecular masses (M(r)s) of 35,000,
      28,000, 24,000, and 20,000 were identified. Of these, the 28- and 35-kDa
      polypeptides were not expressed in detectable quantities in the high-passage B31
      strain, whereas the 24- and 20-kDa proteins were present in reduced quantities.
      All four of these proteins were lipoproteins, as determined by labelling with
      [3H]palmitate. The abundant 28-kDa component, called outer surface protein D
      (OspD), is surface exposed on the basis of its proteolysis during treatment of
      intact organisms with proteinase K. The ospD gene is located on a 38-kb linear
      plasmid present in seven of nine low-passage strains of B. burgdorferi examined
      but absent in most high-passage, nonvirulent strains tested. Molecular cloning
      and sequence analysis of the ospD gene locus revealed an open reading frame
      encoding a 28,436-Da polypeptide with a putative signal peptidase II leader
      sequence. An unusual feature of the region upstream of the gene was the presence
      of seven contiguous, direct repeats of a 17-bp sequence that includes consensus 
      35 and -10 transcription initiation signals; however, only one transcription
      initiation site was active as determined by primer extension analysis. Further
      study of these and other polypeptides associated with low-passage strains may
      lead to identification of B. burgdorferi gene products required for infection and
      pathogenesis in mammalian hosts.

PMID- 1398982
TI  - Activity of defensins from human neutrophilic granulocytes against Mycobacterium
      avium-Mycobacterium intracellulare.
AB  - We have examined the activity of defensins from human neutrophilic granulocytes
      against Mycobacterium avium-Mycobacterium intracellulare. M. avium-M.
      intracellulare at 2.5 x 10(6)/ml or 2.5 x 10(8)/ml was cultured in the presence
      of defensins at 37 degrees C from 4 to 48 h. After incubation, CFU were
      enumerated. Human neutrophil peptide 1 (HNP-1) at 5 micrograms/ml had the ability
      to kill M. avium-M. intracellulare. Treatment with HNP-1 resulted in significant
      (96.3 to 97.7%) killing of M. avium-M. intracellulare, even after taking clumping
      into consideration. This activity was not affected by the presence of calcium
      (0.5 and 1.0 mM), magnesium (0.5 and 1.0 mM), or sodium chloride (25, 50, and 100
      mM). The optimal pH for bactericidal activity was higher than 5. We tested
      numerous M. avium-M. intracellulare strains, and HNP-1 was successful in killing
      every strain, although the degree of killing varied among them (34.2 to 87.2%).
      Additionally, this activity was independent of colonial morphology. We also
      examined the activity of HNP-2 and HNP-3 against M. avium-M. intracellulare and
      found that they were as effective in killing M. avium-M. intracellulare as HNP-1
      was. These observations suggest that defensins may play an important role in the
      host defense against M. avium-M. intracellulare.

PMID- 1398983
TI  - Characterization of a fucoside-binding adhesin of Candida albicans.
AB  - Candida albicans GDH 2346 produces extracellular polymeric material (EP) which
      contains a mannoprotein adhesin with a lectin-like affinity for fucose-containing
      glycosides. EP isolated from culture supernatants of this strain was used as
      starting material for purification of the adhesin. The purification protocol
      involved a stepwise treatment of EP with N-glycanase, papain, and dilute alkali
      to cleave the protein and carbohydrate portions of the mannoprotein molecule.
      Fucoside-binding protein fragments were then recovered by affinity adsorption
      with the trisaccharide determinant of the H (type 2) blood group antigen which
      terminates in a residue of L-fucose. The purified adhesin was devoid of
      carbohydrate and inhibited yeast adhesion to buccal epithelial cells 221 times
      more efficiently, on a protein weight basis, than did EP. Adhesion inhibition
      reached a maximum of 78 to 80% at an adhesin concentration of 10 micrograms ml-1.
      Our results indicate that this protein is the major adhesin of yeast-phase cells
      of C. albicans GDH 2346 but that one or more secondary adhesion mechanisms may
      operate.

PMID- 1398985
TI  - High-affinity binding of the bactericidal/permeability-increasing protein and a
      recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide.
AB  - Bactericidal/permeability-increasing protein (BPI) is a 55-kDa cationic protein
      (nBPI55) elaborated by polymorphonuclear neutrophils (PMN). BPI has potent
      bactericidal activity against a wide variety of gram-negative organisms and
      neutralizes endotoxin activities. An N-terminal fragment of nBPI55 exhibits the
      bactericidal and antiendotoxin properties of the holoprotein. To further
      characterize the biological activities of the N-terminal fragment, a recombinant
      protein (rBPI23) corresponding to the first 199 amino acids of human BPI was
      produced and purified. rBPI23 had antibacterial activity equivalent to that of
      nBPI55 against Escherichia coli J5. Furthermore, both rBPI23 and nBPI55 bound
      identically to a broad range of R- and S-form lipopolysaccharides (LPS) and to
      natural and synthetic lipid A. Binding of radiolabeled nBPI55 to LPS was
      inhibited in an identical fashion by either nBPI55 or rBPI23. The binding of both
      proteins to immobilized E. coli J5 lipid A was inhibited in a comparable fashion
      by long- or short-chain LPS or lipid A. The binding of both rBPI23 and nBPI55 was
      specific, saturable, and of high affinity, with an apparent Kd of approximately 2
      to 5 nM for all ligands tested. These results demonstrate that BPI recognizes the
      highly conserved lipid A region of bacterial LPS via residues contained within
      the amino-terminal portion of the BPI molecule.

PMID- 1398986
TI  - Growth characteristics of recent sputum isolates of Mycobacterium tuberculosis in
      guinea pigs infected by the respiratory route.
AB  - The consideration of virulence must distinguish between infectivity and the
      ability to cause progressive disease once the infection is established. Several
      investigators have reported the presence of naturally occurring isolates which
      differ in virulence for guinea pigs. Isolates from south India which differed
      with respect to gross disease and number of bacilli recovered from spleen after
      an intramuscular infection also differed in their efficiencies to initiate an
      infection, once inhaled and retained. Also, this difference was correlated with
      differences in the rate of multiplication at the site of implantation and rate of
      multiplication at sites of hematogenous seeding, as well as the extent of
      hematogenous seeding. The number of metastatic foci was identified as a
      quantitative measure of hematogenous seeding, which was not confounded by the
      rate of multiplication of bacilli. Even allowing for the fourfold-reduced
      efficiency of low-virulence tubercle bacilli to produce a lesion, this measure
      clearly revealed a significantly reduced ability of the low-virulence tubercle
      bacilli to disseminate via the bloodstream.

PMID- 1398984
TI  - Ability of Proteus mirabilis to invade human urothelial cells is coupled to
      motility and swarming differentiation.
AB  - Proteus mirabilis causes serious kidney infections which can involve invasion of
      host urothelial cells. We present data showing that the ability to invade host
      urothelial cells is closely coupled to swarming, a form of cyclical multicellular
      behavior in which vegetative bacteria differentiate into hyperflagellated,
      filamentous swarm cells capable of coordinated and rapid population migration.
      Entry into the human urothelial cell line EJ/28 by P. mirabilis U6450 isolated at
      different stages throughout the swarming cycle was measured by the antibiotic
      protection assay method and confirmed by electron microscopy. Differentiated
      filaments entered urothelial cells within 30 min and were 15-fold more invasive
      (ca. 0.18% entry in 2 h) than an equivalent dry weight of vegetative cells
      isolated before differentiation, which attained only ca. 0.012% entry in the 2-h
      assay. The invasive ability of P. mirabilis was modulated in parallel with
      flagellin levels throughout two cycles of swarming. Septation and division of
      intracellular swarm cells produced between 50 and 300 vegetative bacteria per
      human cell, compared with 4 to 12 intracellular bacteria after incubation with
      vegetative cells. Transposon (Tn5) mutants of P. mirabilis with specific defects
      in motility and multicellular behavior were compared with the wild-type for the
      ability to invade. Mutants which lacked flagella (nonmotile nonswarming) were
      entirely noninvasive, and those which were motile but defective in swarm cell
      formation (motile nonswarming) were 25-fold less invasive than wild-type
      vegetative cells. Mutants with defects in the coordination of multicellular
      migration and the temporal control of consolidation (cyclical reversion of swarm
      cells to vegetative cells) were reduced ca. 3- to 12-fold in the ability to enter
      urothelial cells. In contrast, a nonhemolytic transposon mutant which swarmed
      normally retained over 80% of wild-type invasive ability. Swarm cells and early
      consolidation cells were at least 10-fold more cytolytic than vegetative cells as
      a result of their high-level production of hemolysin.

PMID- 1398987
TI  - A murine model of chronic mucosal colonization by Pseudomonas aeruginosa.
AB  - Chronic mucosal colonization by Pseudomonas aeruginosa is an integral part of the
      pathologic process associated with disease due to infection with this organism.
      We have adapted the streptomycin-treated murine model of chronic mucosal
      colonization by enteric pathogens to study colonization by P. aeruginosa. Mice
      first received 1 mg of streptomycin per ml of drinking water for 2 to 5 days and
      then ingested 10(7) CFU of P. aeruginosa per ml of drinking water for a minimum
      of 5 days. The result of this regimen was chronic mucosal colonization with P.
      aeruginosa for up to 10 weeks, which was determined by fecal cultures and
      confirmed by culture of the intestines after killing of the experimental animals.
      Bacterial counts were highest in the cecum and colon, with some evidence for
      extraintestinal bacterial translocation as well. Use of P. aeruginosa mutants
      deficient in the production of colonization factors such as pili and those
      dependent on the rpoN gene product resulted in a lower level of chronic
      colonization. Immune responses to type-specific lipopolysaccharide, pili, and
      flagellar antigens were measured, and increases in both serum and intestinal
      antibodies were usually elicited when a strain elaborated a given antigen. This
      model represents an easy method of routinely achieving chronic mucosal
      colonization by P. aeruginosa and should prove useful for the study of both
      bacterial virulence factors and host responses associated with this infectious
      process.

PMID- 1398988
TI  - Purification and characterization of a peptide essential for formation of
      streptolysin S by Streptococcus pyogenes.
AB  - Peptides in a pronase digest of bovine serum albumin were required for
      streptolysin S formation by Streptococcus pyogenes besides maltose and a carrier
      (the oligonucleotide fraction obtained by treatment of Saccharomyces cerevisiae
      RNA with RNase A). A peptide essential for streptolysin S formation was purified
      to homogeneity from a pronase digest of bovine serum albumin by Sephadex G-25
      column chromatography, and anion-exchange, reverse-phase, and gel filtration high
      performance liquid chromatography. The purified peptide was divided into more
      than two peptides by HCOOOH oxidation and was composed of four residues of
      cysteine, three of leucine, and one each of aspartic acid and glutamic acid.
      Leucine and cysteine were detected as amino-terminal residues, and leucine and
      glutamic acid were detected as carboxyl-terminal residues, suggesting that two or
      three peptides are linked by a disulfide bond(s). A disulfide bond structure in
      the peptide seemed to be required for streptolysin S formation.

PMID- 1398989
TI  - Immunization with extracellular proteins of Mycobacterium tuberculosis induces
      cell-mediated immune responses and substantial protective immunity in a guinea
      pig model of pulmonary tuberculosis.
AB  - We have studied the capacity of a selected fraction of Mycobacterium tuberculosis
      extracellular proteins (EP) released into broth culture by mid-logarithmic-growth
      phase organisms to induce cell-mediated immune responses and protective immunity
      in a guinea pig model of pulmonary tuberculosis. Guinea pigs infected with M.
      tuberculosis by aerosol but not uninfected control guinea pigs exhibit strong
      cell-mediated immune responses to EP, manifest by dose-dependent cutaneous
      delayed-type hypersensitivity and splenic lymphocyte proliferation. Guinea pigs
      immunized subcutaneously with EP but not sham-immunized control guinea pigs also
      develop strong cell-mediated immune responses to EP, manifest by dose-dependent
      cutaneous delayed-type hypersensitivity and splenic lymphocyte proliferation. EP
      is nonlethal and nontoxic to guinea pigs upon subcutaneous immunization. Guinea
      pigs immunized with EP and then challenged with aerosolized M. tuberculosis
      exhibit protective immunity. In five independent experiments, EP-immunized guinea
      pigs were consistently protected against clinical illness, including weight loss.
      Compared with EP-immunized guinea pigs, sham-immunized control guinea pigs lost
      12.9 +/- 2.0% (mean +/- SE) of their total weight. EP-immunized guinea pigs also
      had a 10-fold reduction in viable M. tuberculosis bacilli in their lungs and
      spleens (P = 0.004 and 0.001, respectively) compared with sham-immunized control
      animals. In the two experiments in which some guinea pigs died after aerosol
      challenge, EP-immunized animals were protected from death. Whereas all 12 (100%)
      EP-immunized guinea pigs survived challenge with aerosolized M. tuberculosis,
      only 6 of 12 (50%) sham-immunized control guinea pigs survived challenge (P =
      0.007, Fisher exact test). This study demonstrates that actively growing M.
      tuberculosis cells release immunoprotective molecules extracellularly, that a
      subunit vaccine against tuberculosis is feasible, and that extracellular
      molecules of M. tuberculosis are potential candidates for a subunit vaccine.

PMID- 1398990
TI  - Pathogen and host differences in bacterial adherence to human buccal epithelial
      cells in a northeast Brazilian community.
AB  - The adherence of several strains of Escherichia coli to human buccal epithelial
      cells was studied, using cells obtained from five groups: healthy adults, healthy
      children, children with acute diarrhea, children with persistent diarrhea
      associated with cryptosporidial parasites, and children with noncryptosporidial
      persistent diarrhea. All groups lived or worked in an urban slum in northeastern
      Brazil. Samples of buccal epithelial cells from subjects in each of these groups
      were incubated with wild-type E. coli K-12 (strain C600), the enteroaggregative
      E. coli strains 17-2 and PDAS 30-5, CFA/II-positive E. coli 1392+ and its plasmid
      cured derivative 1392-, and hydrophobic E. coli 132-3. Samples were evaluated
      microscopically to determine background contamination and the percentage of cells
      with more than 15% of their surface area obscured by adherent bacteria after
      incubation and washing. The assay was tested under field conditions and was shown
      to produce reliable and consistent results. Both enteroaggregative strains of E.
      coli were shown to adhere to a significantly higher percentage of all groups of
      human buccal epithelial cells than any of the other tested strains. In addition,
      buccal epithelial cells from children with nonparasitic persistent diarrhea
      showed substantially more bacterial adherence in both the native state and with
      all tested strains of E. coli than did cells from children with persistent
      cryptosporidial diarrhea or acute diarrhea or from healthy controls. This study
      provides evidence that enteroaggregative strains of E. coli demonstrate increased
      adherence to human buccal epithelial cells (as well as to cultured HEp-2 cells)
      and that buccal epithelial cells from children with noncryptosporidial persistent
      diarrhea appear to be more susceptible to bacterial adherence and colonization
      than buccal epithelial cells from control groups. These findings suggest that
      host differences as well as pathogen differences are important in the
      pathogenesis of persistent diarrhea and have implications for a potential role
      for buccal epithelial cell analysis in the diagnosis or risk stratification of
      children susceptible to noncryptosporidial persistent diarrhea.

PMID- 1398991
TI  - Opsonization of Streptococcus agalactiae of bovine origin by complement and
      antibodies against group B polysaccharide.
AB  - The contribution of bovine complement and antibodies (Ab) against the group B
      polysaccharidic antigen (GBA) to the opsonization of Streptococcus agalactiae
      isolated from bovine mastitis cases was investigated by using affinity-purified
      Ab. GBA-specific Ab were not opsonic by themselves, but in the presence of
      complement (precolostral calf serum) with an opsonization time of 15 min, they
      exhibited a dose-dependent opsonic activity in a polymorphonuclear leukocyte
      chemiluminescence assay. Kinetic studies of the deposition of complement
      component C3 on protein X-bearing nontypeable (NT/X) strains with an enzyme
      linked immunosorbent assay showed that C3 was deposited on bacteria in the
      absence of Ab but that GBA-specific Ab markedly accelerated the process by
      reducing the lag phase, which extended up to 15 min when Ab were absent. In the
      absence of Ab, C3 deposition was inhibited by 5 mM salicylaldoxime or heat
      treatment at 56 degrees C for 3 min and necessitated Mg2+ ions but not Ca2+ ions,
      suggesting that activation of complement was effected by the alternative pathway
      only. When GBA-specific Ab were added to complement, the inhibitory treatments
      lost much of their efficacy, suggesting that the classical pathway was recruited.
      Deposition of C3 on NT/X strains in the absence of Ab induced chemiluminescence
      and phagocytic killing. With the addition of GBA-specific Ab, the numbers of
      surviving bacteria were halved (P < 0.05) compared with killing in the presence
      of complement alone. It can be concluded that NT/X strains are activators of the
      alternative pathway of complement and that GBA-specific Ab reinforce the opsonic
      efficiency of serum by recruiting the classical pathway and slightly enhancing
      phagocytic killing.

PMID- 1398992
TI  - The platelet interactivity phenotype of Streptococcus sanguis influences the
      course of experimental endocarditis.
AB  - A strain of Streptococcus sanguis that induced rabbit platelets to aggregate in
      vitro (Agg+ phenotype) was hypothesized to be a more virulent pathogen than an
      Agg- strain in experimental endocarditis in rabbits. A left ventricular catheter
      was implanted, and then an Agg+ or Agg- strain was inoculated intravenously.
      Vegetations formed on the aortic semilunar valves but were unaffected by the
      duration of implantation of the catheter. Vegetations enlarged by accumulating
      platelets and their mass increased directly with the duration of endocarditis.
      Inoculation of the Agg+ strain consistently caused endocarditis with
      significantly larger vegetations, a more severe clinical course (including
      febrile episodes, hematological changes, and signs of myocardial ischemia), more
      gross lesions in major organs, and greater mortality than inoculation with the
      Agg- strain, saline, or the Agg+ strain pretreated with monospecific rabbit
      immunoglobulin G or Fab fragments against its platelet aggregation-associated
      protein (PAAP; class II). In experimental endocarditis, PAAP expressed by Agg+ S.
      sanguis appeared to be an important virulence factor.

PMID- 1398994
TI  - Feedback suppression of staphylococcal enterotoxin-stimulated T-lymphocyte
      proliferation by macrophages through inductive nitric oxide synthesis.
AB  - Staphylococcal enterotoxin A (SEA)- or SEB-stimulated T-lymphocyte proliferation
      was suppressed by the addition of high numbers of murine peritoneal macrophages
      or rat peritoneal or alveolar macrophages, whereas lower numbers of murine
      peritoneal macrophages enhanced the T-lymphocyte response. Suppression was
      associated with the increase of accumulation of nitrite, a product of nitric
      oxide, in the culture supernatants. This macrophage-mediated suppression was
      totally reversed by the addition of NG-monomethyl-L-arginine, a homolog of L
      arginine, indicating that macrophage-mediated suppression of T-lymphocyte
      proliferation was mediated through the nitric oxide-synthesizing pathway
      activity. Macrophages in large numbers spontaneously produced nitric oxide in
      culture supernatant fluids. By the addition of autologous or allogeneic spleen
      cells but not thymocytes to SEA- or SEB-stimulated macrophage culture, nitric
      oxide production was greatly increased. When T lymphocytes in spleen cells were
      killed by antibody before addition to macrophage culture, nitric oxide production
      was diminished to the basal level. These results suggest that in addition to the
      action to support the process of T-lymphocyte activation by SEA or SEB,
      macrophages display a feedback regulatory action on the SEA- or SEB-stimulated T
      cell proliferative response by releasing nitric oxide through interaction between
      macrophages and activated T lymphocytes.

PMID- 1398993
TI  - Opsonic antibody activity against Actinobacillus actinomycetemcomitans in
      patients with rapidly progressive periodontitis.
AB  - Actinobacillus actinomycetemcomitans has been closely associated with early
      onset, severe periodontitis, and such patients often have serum immunoglobulin G
      (IgG) antibodies reactive with antigens of this gram-negative pathogen. We
      examined the functionality and potential importance of these antibodies. The
      opsonic activity against A. actinomycetemcomitans of sera from 30 patients with
      rapidly progressive periodontitis (RPP) and from 28 periodontally normal subjects
      was tested by using polymorphonuclear leukocyte (PMN) chemiluminescence and
      bactericidal assays. Peak chemiluminescence values correlated strongly with
      killing observed in the PMN-dependent bactericidal assay (r = 0.88; P < 0.001).
      Neither the mean IgG titer nor the mean peak chemiluminescence differed
      significantly between the two groups. However, when the relationship between
      chemiluminescence and titer was examined, regression analysis showed that
      antibodies present in low-titer normal sera were significantly more effective at
      opsonizing A. actinomycetemcomitans than antibodies present in low-titer RPP
      patient sera (P = 0.04). Thus, periodontally normal individuals may be better
      able than RPP patients to clear A. actinomycetemcomitans in early stages of
      colonization, and anti-A. actinomycetemcomitans antibodies in RPP patients may be
      relatively ineffective in preventing infection by this organism.

PMID- 1398995
TI  - Complement activation by polyclonal immunoglobulin G1 and G2 antibodies against
      Staphylococcus aureus, Haemophilus influenzae type b, and tetanus toxoid.
AB  - To obtain information on effector functions of human immunoglobulin G2 (IgG2), we
      have measured the complement-activating properties of polyclonal IgG subclass
      antibodies against bacterial antigens. IgG1 and IgG2 were purified from serum
      samples from five healthy individuals, and complement activation was measured
      with different bacterial antigens. We used Staphylococcus aureus Wood 46 (STAW),
      which is a common antigen, Haemophilus influenzae type b (Hib), which is a common
      pathogenic microorganism in children, and formaldehyde-inactivated tetanus toxin
      (TT). Bacteria were incubated with antibodies and then incubated with sera from
      agammaglobulinemic patients as a complement source, and C3c deposition was
      measured by enzyme-linked immunosorbent assay. We found that anti-STAW IgG2
      activated complement to a level similar to that of anti-STAW IgG1. Anti-Hib IgG1
      complement activation was as much as seven times higher than that of anti-Hib
      IgG2 in four individuals. In one individual, anti-Hib IgG2 was more effective in
      complement activation than anti-Hib IgG1. Anti-TT antibodies showed patterns
      similar to those of anti-Hib. Our results indicate that IgG2 antibodies may
      contribute significantly to antibacterial defense. Also, individual differences
      in antibody effector functions should be taken into account when evaluating the
      immune status of patients and during early phase 1 studies of new vaccines.

PMID- 1398996
TI  - Major outer membrane proteins of Vibrio cholerae and their role in induction of
      protective immunity through inhibition of intestinal colonization.
AB  - Vibrio cholerae O1 organisms belonging to different biotypes and serotypes were
      shown to express major outer membrane proteins (MOMPs) with subunit molecular
      masses of 48 to 50, 40 to 43, 35 to 36, 27 to 28, and 20 kDa. Antisera raised
      against individual MOMPs of a V. cholerae O1 strain recognized MOMPs of
      corresponding molecular masses in other O1 and non-O1 strains. Serological data
      also suggested possible differences in the cell surface exposition of these
      MOMPs. However, no marked differences between V. cholerae cells grown in vitro
      and in vivo could be noted in respect to the expression or surface exposition of
      these MOMPs. Of five MOMPs studied in this work, 40- to 43- and 20-kDa cell
      surface proteins were shown to be of considerable importance, as antisera to
      these proteins induced significant protection against V. cholerae challenge in
      the suckling mouse model. Similar protection, although to a lesser extent, was
      demonstrable with the antiserum to the 27- to 28-kDa protein. These results were
      corroborated with the Fab (immunoglobulin G) [Fab(IgG)] fragments of the
      antisera, thereby suggesting that the observed protection induced by anti-MOMP
      antibodies did not arise as a result of bacterial clumping. Subsequent studies
      demonstrated that these antisera as well as their Fab (IgG) fragments induced
      significant inhibition of intestinal colonization of V. cholerae. The 40- to 43-
      and 27- to 28-kDa proteins appeared to be porinlike, while the 20-kDa protein was
      found to be antigenically related to TcpA (subunit A of toxin-coregulated pilus).
      All these results demonstrate the involvement of more than one cell surface
      antigen of V. cholerae in the induction of protective immunity through inhibition
      of intestinal colonization of vibrios.

PMID- 1398997
TI  - Phagocytosis and killing of Actinobacillus pleuropneumoniae by alveolar
      macrophages and polymorphonuclear leukocytes isolated from pigs.
AB  - To study the cellular response of phagocytic cells to Actinobacillus
      pleuropneumoniae, we investigated whether porcine alveolar macrophages (AM) and
      polymorphonuclear leukocytes (PMN) are able to phagocytize and intracellularly
      kill A. pleuropneumoniae in vitro. Bacterial cultivation methods of A.
      pleuropneumoniae were used to assess in vitro phagocytosis and the ability to
      kill. A specific-pathogen-free pig was killed, blood was collected, and PMN were
      isolated and counted. The AM were isolated by lung lavage of the same animal and
      counted. In addition, convalescent-stage serum was collected from a specific
      pathogen-free pig that was infected with A. pleuropneumoniae. Both porcine AM and
      porcine PMN effectively phagocytized A. pleuropneumoniae in the presence of
      convalescent-stage pig serum. PMN killed 90 to 99% of the bacteria
      intracellularly, whereas AM did not. Because A. pleuropneumoniae produces
      exotoxins that kill porcine AM and porcine PMN, we incubated equal amounts of
      bacteria and phagocytic cells and tested the viability of the cells 120 min
      later. In the presence of convalescent-stage pig serum, A. pleuropneumoniae was
      toxic to AM but not to PMN. Probably in porcine AM, intracellular released toxins
      of A. pleuropneumoniae lessen the ability of the cell to kill the bacterium.
      Consecutive lysis of AM and release of viable A. pleuropneumoniae may initiate
      the characteristic porcine pleuropneumonia.

PMID- 1398998
TI  - Electrophoretic karyotypes of clinical isolates of Coccidioides immitis.
AB  - Chromosomes of the fungal respiratory pathogen, Coccidioides immitis, were
      separated by contour-clamped homogeneous electric field gel electrophoresis.
      Twelve isolates were examined, the majority of which showed four chromosomes with
      a range of molecular size from 11.5 to 3.2 Mb. Three isolates (C634, C735, and L)
      revealed three chromosomal bands under the conditions employed for
      electrophoretic separation. However, in two of these isolates (C634 and C735),
      four chromosomes were visible on membrane transfers of pulsed-field gels after
      Southern hybridization between the chromosomal DNA and selected DNA probes. The
      probes included a conserved ribosomal gene and three previously described cDNAs
      isolated from C. immitis expression libraries. The L isolate was determined to
      have the same genome size as a typical four-chromosome isolate on the basis of
      microspectrophotometric comparison of fluorescence intensity of the ethidium
      bromide-stained nuclear DNA. The genome size of C. immitis determined by
      microspectrophotometry was approximately 28.2 +/- 2.6 Mb. The calculated genome
      size based on addition of the average molecular weights of chromosomal bands
      separated by contour-clamped homogeneous electric field gel electrophoresis was
      approximately equal to the estimate derived from the spectrophotometric analyses.
      This is the first report of the electrophoretic karyotype of C. immitis.

PMID- 1398999
TI  - Characterization and protective properties of attenuated mutants of Salmonella
      choleraesuis.
AB  - We have constructed crp::Tn10 and cya::Tn10 Salmonella choleraesuis mutants and
      their fusaric acid-resistant derivatives with deletions (delta) of the Tn10 and
      adjacent DNA sequences and found them to be avirulent and able to induce
      protection against a wild-type challenge in 8-week-old BALB/c mice. Mice survived
      infection with the crp and cya mutants at doses of more than 7 x 10(3) times the
      oral (p.o.) 50% lethal dose (LD50) and more than 8 x 10(2) times the
      intraperitoneal LD50 of the wild-type S. choleraesuis parent. Mice vaccinated
      with attenuated strains were protected against challenge with more than 1.6 x
      10(4) times the p.o. LD50 and more than 80 times the intraperitoneal LD50 of the
      wild-type virulent S. choleraesuis parent. One deletion mutation isolated in the
      crp region extends to an adjacent gene(s) that was shown to be associated with
      avirulence. This gene or operon has been designated cdt (colonization of deep
      tissues). A delta (crp-cdt)19 strain, when complemented with the wild-type crp
      gene and promoter on a pBR-derived plasmid, had p.o. LD50 values 10(3) times
      higher than those for the wild type. A delta cya delta (crp-cdt)19 double mutant
      was less virulent than and afforded more complete protection against a challenge
      with the wild-type strain than a delta crp-11 delta cya double mutant or the
      individual cya, crp, or crp+/cdt mutants. The deletion derivatives exhibited
      reduced invasion of CHO cells in vitro, and the numbers of the mutants recovered
      from mouse tissues were less than that of the parent strain. These studies
      suggest that one or more of the genes involved in cell attachment to and/or
      invasion of S. choleraesuis may be under catabolite repression. In addition, we
      describe a new deletion of a gene(s) located in the crp region between cysG and
      argD that is associated with virulence in S. choleraesuis.

PMID- 1399000
TI  - Roles of peripheral leukocytes and tissue macrophages in antibacterial resistance
      induced by free or liposome-encapsulated muramyl tripeptide
      phosphatidylethanolamide.
AB  - Administration of free muramyl tripeptide phosphatidylethanolamide (MTPPE) or
      liposome-encapsulated MTPPE (LE-MTPPE) in a twofold-lower dose at 24 h before
      bacterial inoculation resulted in clearance of intravenously inoculated
      Klebsiella pneumoniae by tissue macrophages, whereas in control mice, bacteria
      were not effectively cleared from the blood. In addition, MTPPE and LE-MTPPE led
      to increased numbers of leukocytes in the blood, which could compensate for the
      leukopenia in mice resulting from infection with K. pneumoniae. In an attempt to
      elucidate the relative contributions of the activation of tissue macrophages and
      the recruitment of leukocytes to the antibacterial resistance induced by MTPPE
      and LE-MTPPE, mice were infected intraperitoneally with K. pneumoniae. In these
      MTPPE- and LE-MTPPE treated mice, intraperitoneal influx of leukocytes and the
      phagocytic capacity of leukocytes were not higher than in untreated control mice.
      However, MTPPE- and LE-MTPPE-treated mice survived much longer; eventually 33% of
      the LE-MTPPE-treated mice survived, whereas all untreated control mice died as a
      result of bacterial septicemia. This prevention of early death appeared to be the
      result of an increased clearance of bacteria from the blood by activated tissue
      macrophages. It was observed that depletion of these tissue macrophages in liver
      and spleen abrogates the effect of LE-MTPPE treatment, indicating that tissue
      macrophages are of major importance in the LE-MTPPE-induced resistance against K.
      pneumoniae infection.

PMID- 1399001
TI  - Gastrointestinal colonization and systemic dissemination by Candida albicans and
      Candida tropicalis in intact and immunocompromised mice.
AB  - Gastrointestinal colonization and systemic dissemination by Candida albicans and
      Candida tropicalis were compared in intact and immunocompromised mice. Five-day
      old CFW mice were inoculated by the oral-intragastric route with 1.0 x 10(7) CFU
      of two C. albicans and two C. tropicalis strains isolated from the blood of
      patients with acute leukemia and with C. albicans 4918 and its cerulenin
      resistant mutant 4918-10. C. albicans and C. tropicalis spread to the lungs,
      liver, and kidneys within 30 min postinoculation, and organ CFU of the two
      species were comparable over the following 10 days. Close association of
      blastoconidia with the villous surface of the small intestine resulted in lysis
      of microvilli and then progressive invasion of villi. Blastoconidia within villi
      were surrounded by a conspicuous zone of clearing. Persistent colonization of the
      small and large intestines by C. albicans blood isolates and strains 4918 and
      4918-10 was similar for 31 days after inoculation, but consistently exceeded that
      of C. tropicalis. In mice colonized with C. albicans, immunosuppression with
      cortisone acetate and cyclophosphamide on days 30 and 33 after inoculation
      increased stomach CFU 40- to 370-fold and intestinal CFU 30- to 80-fold. In
      contrast, persistent colonization by C. tropicalis was undetectable before
      immunosuppression and only became apparent after treatment. C. albicans
      disseminated more frequently and with higher organ CFU than C. tropicalis.
      Despite this fact, 20% of mice infected with C. tropicalis died, compared with 4%
      infected with C. albicans blood isolates. Indirect immunofluorescence revealed
      penetrative growth by Candida hyphae exclusively in the mucosa and submucosa of
      the stomach from immunosuppressed, persistently colonized mice. Taken together,
      the data indicate that C. tropicalis appears to be more virulent than C. albicans
      and that factors responsible for gastrointestinal colonization, systemic
      dissemination, and mortality in immunocompromised mice may not be identical.

PMID- 1399002
TI  - Fusion proteins containing the A2 domain of cholera toxin assemble with B
      polypeptides of cholera toxin to form immunoreactive and functional holotoxin
      like chimeras.
AB  - Cholera enterotoxin (CT) is produced by Vibrio cholerae and excreted into the
      culture medium as an extracellular protein. CT consists of one A polypeptide and
      five B polypeptides associated by noncovalent bonds, and CT-B interacts with CT-A
      primarily via the A2 domain. Treatment of CT with trypsin cleaves CT-A into A1
      and A2 fragments that are linked by a disulfide bond. CT-B binds to ganglioside
      GM1, which functions as the plasma membrane receptor for CT, and the enzymatic
      activity of A1 causes the toxic effects of CT on target cells. We constructed
      translational fusions that joined foreign proteins via their carboxyl termini to
      the A2 domain of CT-A, and we studied the interactions of the fusion proteins
      with CT-B. The A2 domain was necessary and sufficient to enable bacterial
      alkaline phosphatase (BAP), maltose-binding protein (MBP) or beta-lactamase (BLA)
      to associate with CT-B to form stable, immunoreactive, holotoxin-like chimeras.
      Each holotoxin-like chimera was able to bind to ganglioside GM1. Holotoxin-like
      chimeras containing the BAP-A2 and BLA-A2 fusion proteins had BAP activity and
      BLA activity, respectively. We constructed BAP-A2 mutants with altered carboxyl
      terminal sequences and tested their ability to assemble into holotoxin-like
      chimeras. Although the carboxyl-terminal QDEL sequence of the BAP-A2 fusion
      protein was not required for interaction with CT-B, most BAP-A2 mutants with
      altered carboxyl termini did not form holotoxin-like chimeras. When holotoxin
      like chimeras containing BAP-A2, MBP-A2, or BLA-A2 were synthesized in V.
      cholerae, they were found predominantly in the periplasm. The toxin secretory
      apparatus of V. cholerae was not able, therefore, to translocate these holotoxin
      like chimeras across the outer membrane.

PMID- 1399003
TI  - Laminin on Toxoplasma gondii mediates parasite binding to the beta 1 integrin
      receptor alpha 6 beta 1 on human foreskin fibroblasts and Chinese hamster ovary
      cells.
AB  - We investigated the role of parasite-bound laminin and the host cell beta 1
      integrin receptors for this extracellular matrix protein in Toxoplasma gondii
      binding to fibroblasts. Laminin but not fibronectin was detected on extracellular
      tachyzoites by immunofluorescence and immunoblotting. Binding of parasites to CHO
      cells was inhibited by polyclonal antibodies to laminin and by a monoclonal
      antibody directed against the globular carboxyl-terminal portion of the long arm
      of laminin (at or near the suggested ligand-binding sites for alpha 3 beta 1 and
      alpha 6 beta 1), but not by a monoclonal antibody directed against the lateral
      short arms of laminin near the cross region of the molecule. Antibodies to the
      alpha 6 but not the alpha 2, alpha 3, or alpha 5 chains of the beta 1 family of
      integrins blocked parasite attachment to human foreskin fibroblasts and CHO
      cells. Attachment of T. gondii to cells via laminin on the parasite surface and
      laminin receptors on the mammalian cell is consistent with the capacity of the
      parasite to invade almost all nucleated cells.

PMID- 1399004
TI  - Human immune response to Campylobacter jejuni proteins expressed in vivo.
AB  - Campylobacter jejuni 81-176 grown in vivo in rabbit ileal loops expresses novel
      proteins that are not expressed under standard laboratory culture conditions. A
      new protein with a molecular mass of ca. 180 kDa is expressed at 14, 24, and 48 h
      of infection. Three other proteins, with molecular masses of ca. 66, 43, and 35
      kDa, are overexpressed during different phases of infection. Expression of these
      proteins stops immediately during the first passage in laboratory media, and they
      do not elicit a human immune response. Two other proteins, with molecular masses
      of ca. 84 and 47 kDa, expressed 48 h after infection can be identified by using
      convalescent sera from human volunteers who were immune to C. jejuni infection
      upon rechallenge; these proteins were not visualized on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis gels by Coomassie blue staining or silver
      staining. Antibodies to the 84- and 47-kDa proteins are of the immunoglobulin G
      class. Both preinfection and convalescent human sera react strongly to the C.
      jejuni flagellin (a 58-kDa protein), suggesting the presence of cross-reactive
      antibodies to this protein in healthy humans. Major outer membrane protein and
      flagella may play a role in providing protection against C. jejuni disease, but
      our data suggest that there are other proteins expressed only during in vivo
      growth of the organism that elicit a strong immune response in human C. jejuni
      infections.

PMID- 1399005
TI  - Altered synthetic response of Campylobacter jejuni to cocultivation with human
      epithelial cells is associated with enhanced internalization.
AB  - Campylobacter jejuni has been shown to bind to and enter epithelial cells in
      culture. The interaction of C. jejuni with INT 407 epithelial cells was examined
      to determine whether bacterial protein synthesis is required for either binding
      or internalization. Chloramphenicol, a selective inhibitor of bacterial protein
      synthesis, significantly reduced the internalization, but not binding, of C.
      jejuni compared with untreated controls as determined by protection from
      gentamicin. Electrophoretic analysis of metabolically labeled proteins revealed
      that C. jejuni cultured with INT 407 cells synthesized 14 proteins that were not
      detected in organisms cultured in medium alone. The inhibitory effect of
      chloramphenicol on internalization was reduced by preincubation of C. jejuni with
      INT 407 cells. The results indicate that C. jejuni, like some other enteric
      pathogens, engages in a directed response to cocultivation with epithelial cells
      by synthesizing one or more proteins that facilitate internalization and suggest
      that this phenomenon is relevant to the pathogenesis of enteritis caused by C.
      jejuni.

PMID- 1399007
TI  - Effect of immunization with Freund's adjuvant and pneumolysin on histologic
      features of pneumococcal infection in the rat lung in vivo.
AB  - Immunization with Freund's adjuvant and pneumolysin and stimulation with Freund's
      adjuvant alone both reduced the severity of the pneumonia caused by injections of
      bacteria into the apical lobe bronchi of rats. Neither protocol influenced the
      incidence of pneumococcal bacteremia. Illness sufficiently severe to require
      sacrifice was delayed from 2.8 days in nonimmunized animals to 5.7 days in those
      immunized with Freund's adjuvant and pneumolysin (P < 0.05) and 4.5 days in those
      stimulated with Freund's adjuvant alone (P, not significant).

PMID- 1399006
TI  - Role of the adhesion molecule lymphocyte function associated antigen 1 in toxic
      shock syndrome toxin 1-induced tumor necrosis factor alpha and interleukin-1 beta
      secretion by human monocytes.
AB  - We previously demonstrated that the induction by staphylococcal toxic shock
      syndrome toxin 1 (TSST-1) of tumor necrosis factor alpha (TNF-alpha) and
      interleukin-1 beta (IL-1 beta) secretion by human monocytes requires direct T
      cell-monocyte contact. In the present study, a role for the adhesion molecule
      lymphocyte function associated antigen 1 (LFA-1) in TSST-1-induced cytokine
      secretion by human monocytes among 12 normal healthy donors was investigated.
      Monoclonal antibodies to the alpha chain (anti-CD11a) and to the beta chain (anti
      CD18) of LFA-1 significantly inhibited TSST-1-induced TNF-alpha and IL-1 beta
      secretion (P < 0.025; Wilcoxon signed-rank test, two tailed), while a control
      monoclonal antibody directed against the monocyte CD14 antigen had no effect.
      These results suggest that LFA-1 may play an important role in the secretion of
      TNF-alpha and IL-1 beta by TSST-1-stimulated human monocytes, likely by promoting
      cell-cell adhesion between monocytes and lymphocytes.

PMID- 1399008
TI  - Human neutrophil azurocidin synergizes with leukocyte elastase and cathepsin G in
      the killing of Capnocytophaga sputigena.
AB  - Azurocidin was purified in the presence of phenylmethylsulfonyl fluoride.
      Electrophoresis revealed at least seven species which exhibited N-terminal
      sequences consistent with azurocidin. Azurocidin exhibited no bactericidal
      activity against Capnocytophaga sputigena or other oral bacteria but synergized
      the bactericidal activity of enzymatically active elastase. Azurocidin also
      interacted synergistically with cathepsin G.

PMID- 1399011
TI  - Use of pharmaceuticals in industrial workers--possible implications for
      epidemiological studies.
AB  - A total of 129 workers exposed to carbon disulphide (CS2) and 81 non-exposed
      controls were asked about their current use of pharmaceuticals, using a self
      administered questionnaire. In all, 31% of the exposed and 19.8% of the non
      exposed used some medicine (P = 0.08). The average number of pharmaceuticals per
      subject amounted to 0.71 in the exposed vs. 0.36 in the non-exposed (P = 0.049).
      Predominant types of medicines used were analgesics (12.4% in the exposed vs.
      8.6% in the non-exposed, P = 0.50) and sedatives/hypnotics (10.1% in the exposed
      vs. 4.9% in the non-exposed, P = 0.21). The pharmaceuticals consumed can cause
      numerous (side) effects that are similar to the toxic effects of CS2. To take
      into account these possibly confounding agents, a classification system for
      possible (side) effects of pharmaceuticals was developed, taking the dose into
      account. According to this method, many (side) effects of pharmaceuticals that
      could occur were recorded with higher frequency and intensity in the exposed
      subjects. Potential (side) effects that occurred significantly more frequently in
      the exposed than in the non-exposed were: tiredness, sedation, dizziness (20.9%
      vs. 4.9%, P = 0.001), excitation, anxiety (10.9% vs. 2.5%, P = 0.03), vision
      disturbances (7.0% vs. 0%, P = 0.01), and erection decrease (5.4% vs. 0%, P =
      0.045). The implications of these findings for epidemiological studies are
      discussed.

PMID- 1399010
TI  - Exposure to soluble barium compounds: an interventional study in arc welders.
AB  - Soluble barium (Ba) compounds are well-known toxicants. Intoxications are mainly
      known in an acute form from casual or suicidal oral ingestion. No scientifically
      based data are available on possible health effects of inhalative exposure to
      soluble Ba salts at the workplace. Therefore, we investigated 18 welders in an
      interventional study over 1 week. They performed welding of Ba-containing stick
      electrodes and self-shielded flux cored wires under conditions similar to real
      working conditions. The welding fumes contained 31%-37% Ba, more than 90% of
      which was soluble in acids. Without appropriate preventive measures, a high rate
      of measurements exceeded the TLV values for total welding fumes of 5 mg/m3 and
      for soluble Ba of 0.5 mg/m3. The median fume concentrations were 13.2 mg/m3 in
      stick electrode welding and 12.3 mg/m3 in flux cored wire welding. The median Ba
      concentrations were 4.4 and 2.0 mg/m3 respectively. An integrated exhaust system
      built into the gun proved to be efficient in flux cored wire welding. The
      internal exposure to Ba reached median urine levels up to 101.7 micrograms/l
      (normal: below 20 micrograms/l) and median plasma concentrations of up to 24.7
      micrograms/l (normal: below 8 micrograms/l). No health impact on the welders
      could be proven, but hypokalemia may have occurred as a result of the Ba
      exposure.

PMID- 1399009
TI  - Human factors in firefighting: ergonomic-, cardiopulmonary-, and psychogenic
      stress-related issues.
AB  - There are many issues in firefighting that involve human factors and
      cardiopulmonary conditioning. Population-based mortality and disability
      surveillance studies suggest a relatively small but significant excess of
      disability but not mortality from nonmalignant cardiovascular disease for
      firefighters. More targeted cohort and case-control studies do not support such
      an excess and instead suggest a strong healthy worker effect. Pulmonary function
      among firefighters has been extensively studied, with contradictory findings.
      Extreme exposures and long-term exposure in combination with cigarette smoking
      may be risk factors for respiratory disorders and accelerated decline in airflow.
      It appears likely that individual firefighters who show early signs of illness
      are often selectively transferred out of active firefighting positions. Despite
      exposure to substances such as carbon monoxide that may predispose to
      cardiovascular mortality and morbidity, excesses are not consistently shown in
      mortality studies. Clinical studies of individual firefighters do suggest an
      elevated risk for myocardial ischemia. The ergonomic demands of firefighting are
      extreme at peak activity because of high energy costs for activities such as
      climbing aerial ladders, the positive heat balance from endogenous and absorbed
      environmental heat, and encumbrance by bulky but necessary protective equipment.
      The psychological stresses of firefighting include long periods of relative
      inactivity punctuated by highly stressful alarms and extremely stressful
      situations such as rescues, as reflected in physiological and biochemical
      indicators. Firefighters are at risk for depression and post-traumatic stress
      disorder, although morale overall is generally much higher than in comparable
      occupations. Women firefighter candidates as a group perform less well on
      selection test simulating the demands of active firefighting, but some individual
      women perform very well.

PMID- 1399013
TI  - Changing cancer risk pattern among Finnish hairdressers.
AB  - A cohort of 3637 female and 168 male hair-dressers in Finland was followed up for
      cancer through the Finnish Cancer Registry in 1970-1987. Compared with the total
      population, the women had a significantly elevated risk (standardized incidence
      ratio 1.7) during the first third of the observation period, but not thereafter.
      For the total follow-up period, the relative risks were highest for nonmelanoma
      skin cancer (2.0), lung cancer (1.7), ovarian cancer (1.6), cervical cancer
      (1.5), and cancer of the pancreas (1.5); only the risk of ovarian cancer was
      statistically significant. A decrease in relative risk with time was observed for
      many primary sites, e.g., pancreas, cervix uteri, central nervous system, and
      thyroid. The opposite was true for lung and skin: An increased risk was found
      only in 1982-1987. The excess was most prominent in the oldest age groups with
      the longest time span since the first employment as a hairdresser. Among men,
      too, the general cancer risk was highest (1.6) during the first third of the
      observation period. An excess of cancers of the lung and the pancreas was
      observed. The small numbers, however, did not allow any further conclusions. The
      changes in the cancer risk pattern over time may be associated with changes in
      working conditions in hairdressing salons.

PMID- 1399012
TI  - Immunological findings and respiratory function in cotton textile workers.
AB  - Immunological parameters were studied in a group of 24 cotton textile workers.
      These were volunteers from a cohort of 106 (83 women and 23 men) previously
      studied textile workers. A group of 30 employees from a bottle packing plant
      served as a control for the immunologic studies. The subgroup of volunteers
      undergoing immunologic testing did not differ from the original cohort of textile
      workers in age, sex, smoking history, or prevalence of most chronic respiratory
      symptoms, nor were there any significant differences in baseline lung function or
      across-shift changes. The 24 cotton worker volunteers underwent skin testing with
      extracts of cotton dust and cotton seed. Eight of these 24 (33.3%) had positive
      tests, and 5 of the 8 had elevated serum immunoglobulin E (IgE) levels. Only one
      of the 8 skin-test-positive workers had symptoms of byssinosis. Only 1 of 30
      control workers' skin tested with cotton extract reacted, and none had an
      increased serum IgE level (P less than 0.01). Both baseline lung function and
      across-shift changes did not differ between workers with positive and negative
      skin test reactions or between workers with normal and elevated IgE levels.
      Additionally, we studied the response in vitro of nonsensitized guinea pig
      trachea to cotton bract extract and demonstrated a dose-dependent contractile
      response. These data suggest that while immunological findings are frequent in
      textile workers, they correlate poorly with respiratory symptoms and function and
      may not be the basis for the airway obstruction seen in this disease.

PMID- 1399014
TI  - Investigations on health hazards of chimney sweeps in Germany: results of a
      follow-up study.
AB  - Within the framework of a longitudinal study, 127 chimney sweeps from the area of
      Upper and Middle Franconia (Bavaria, Germany), who had participated in a first
      medical check-up in 1974, were offered follow-up examinations in 1990. Eighty-one
      subjects participated in these examinations; in addition individual occupational
      case histories and medical case histories were obtained for a further 15 and 35
      chimney sweeps, respectively. Five test subjects had died before the evaluation
      deadline (August 15, 1990). The causes of death were a non-Hodgkin's lymphoma, a
      bladder carcinoma, pulmonary metastases with unknown primary tumour, a suicide
      and an acute myocardial infarction. Conspicuous results were carcinoma of the
      oesophagus in one case and leucoplakia of the mucous membranes in the mouth and
      pharyngeal region in three cases; furthermore one chimney sweep had two
      haemorrhagic lumps on his vocal cords. Taking into account important non
      occupational hazards (alcohol and nicotine abuse) as possible causes of these
      changes and the lack of relevant occupational exposure to products of
      incineration over a number of years, none of these cases nor any of the other
      ascertained results could be considered likely to be causally related to
      occupational activities. Due to the small number of cases, an epidemiological
      risk evaluation did not seem useful. Comparison with the results of other chimney
      sweep studies published in the international literature is not helpful due to the
      differences in study design, the varying case frequencies, and the different
      conditions of exposure.

PMID- 1399015
TI  - Assessment of thyroid, testes, kidney and autonomic nervous system function in
      lead-exposed workers.
AB  - The objective of the study was to assess whether moderate occupational exposure
      to lead may be associated with early changes in potential target organs (thyroid,
      testes, kidney, autonomic nervous system). Workers exposed to lead in a lead acid
      battery factory (n = 98; mean blood lead 51 micrograms/dl, range 40-75
      micrograms/dl) and 85 control workers were examined. None of the indicators of
      kidney function (in urine: retinol-binding protein, beta 2-microglobulin,
      albumin, N-acetyl-beta-D-glucosaminidase; in serum: creatinine, beta 2
      microglobulin), endocrine function (follicle-stimulating hormone, luteinizing
      hormone, thyroid-stimulating hormone, thyroxine, triiodothyronine) and autonomic
      nervous system (R-R interval variations on the electrocardiogram) were correlated
      with lead exposure (blood lead or duration of exposure) or showed significantly
      different mean values between the exposed group and controls. These results and
      an assessment of the published data suggest that compliance with the Directive of
      the Council of the European Communities on lead exposure (health surveillance in
      workers whose lead in blood exceeds 40 micrograms/dl and removal from exposure
      when blood lead exceeds 70-80 micrograms/dl) would prevent the occurrence of
      significant biological changes in the majority of lead-exposed workers.

PMID- 1399016
TI  - Occupational risk factors for congenital heart disease.
AB  - To investigate possible associations between cardiovascular malformations and
      maternal occupational exposure to various factors during the first trimester of
      pregnancy, 406 cases and 756 controls were studied retrospectively. The cases
      were taken from all infants diagnosed with cardiovascular malformations born in
      Finland during 1982 and 1983. The controls were randomly selected from all normal
      births in the country during the same period. All mothers were interviewed
      approximately 3 months after delivery by a midwife, using a structured
      questionnaire. Maternal overall exposure to chemicals at work was more prevalent
      among the case group (35.8%) than the control group (26.2%, P less than 0.01).
      Among the specific chemical groups, maternal exposure to dyes, lacquers, or
      paints was significantly associated with the risk of congenital heart disease.
      Exposure to organic solvents during the first trimester seemed to increase to
      risk of ventricular septal defect (P less than 0.05). Work at video display
      terminals was slightly more prevalent among the case group (6.3%) than among the
      control group (5.0%). The mothers' education level, regular exposure to passive
      smoking at work, or temperature at the workplace were not risk factors for
      congenital heart disease in the offspring, neither was maternal exposure to
      microwave ovens, disinfectants, pesticides, or anesthetic gases. It is concluded
      that many maternal exposures at work seem not to have a teratogenic effect on the
      fetal heart, although the limited power of this investigation needs to be borne
      in mind.

PMID- 1399017
TI  - Increase in sister chromatid exchange rates in association with occupational
      exposure to N,N-dimethylformamide.
AB  - The effects of occupational exposure to N,N-dimethylformamide (DMF) on sister
      chromatid exchange (SCE) rates were studied in peripheral lymphocytes from 22 DMF
      exposed women (aged 22-52 years) in comparison with 22 sex-, age-, and residence
      matched controls. All subjects were nonsmokers and nondrinkers as confirmed by
      medical interview. The 22 pairs were divided by the intensity of exposure to DMF
      into 3 subgroups of high-exposed (8 pairs with mean DMF exposure at 5.8 ppm),
      middle-exposed (5 pairs with DMF at 0.7 ppm in combination with toluene at 0.9
      ppm), and low-exposed (9 pairs with DMF at 0.3 ppm). The SCE rates were
      significantly higher in the high (P less than 0.005) and middle (P less than
      0.01) exposed than in their matched pairs, and the increase was related to the
      intensity of DMF exposure.

PMID- 1399018
TI  - Elevated urinary thioether excretion among bidi rollers exposed occupationally to
      processed tobacco.
AB  - Manufacture of bidis - the Indian version of cigarettes - is one of the largest
      cottage industries in India. Bidi rollers handle 225-450 g of bidi tobacco per
      day and inhale tobacco dust and volatile components present in the work
      environment. Since tobacco is known to be mutagenic and carcinogenic, urinary
      cotinine was estimated in bidi rollers and control subjects as an index of
      tobacco-specific exposure while the concentration of urinary thioethers was
      determined to ascertain exposure to electrophilic moieties. Detection of cotinine
      in urine samples from bidi rollers with no tobacco habits indicated that
      occupational exposure leads to cutaneous absorption of tobacco constituents and
      the resultant increase in exposure to alkylating agents was evident from elevated
      urinary thioether levels.

PMID- 1399019
TI  - Occupational exposure to antineoplastic agents at several departments in a
      hospital. Environmental contamination and excretion of cyclophosphamide and
      ifosfamide in urine of exposed workers.
AB  - The occupational exposure to cyclophosphamide (CP), ifosfamide (IF), 5
      fluorouracil (5FU), and methotrexate (MTX) of 25 pharmacy technicians and nurses
      from four departments of a hospital was investigated. Previously developed
      methods for the detection of exposure to some antineoplastic agents were
      validated. Exposure to CP, IF, 5FU, and MTX was measured by the analysis of these
      compounds in the environment (air samples and wipe samples from possible
      contaminated surfaces and objects). Contamination of the work environment was
      found not only on the working trays of the hoods and on the floors of the
      different rooms but also on other objects like tables, the sink unit, cleaned
      urinals and chamber pots, and drug vials and ampules used for preparation and
      packing of drugs. The gloves used during preparation of the drugs and during
      cleaning of the hoods were always contaminated. The uptake of CP or IF was
      determined by the analysis of both compounds in urine. CP or IF was detected in
      the urine of eight pharmacy technicians and nurses. The amounts ranged from less
      than 0.01 to 0.5 micrograms (median: 0.1 microgram). CP and IF were found not
      only in the urine of pharmacy technicians and nurses actively handling these
      compounds (n = 2) but also in the urine of pharmacy technicians and nurses not
      directly involved in the preparation and administration of these two drugs (n =
      6). CP and IF were excreted during different periods ranging from 1.40 to 24.15h
      after the beginning of the working day, suggesting different times of exposure,
      different exposure routes, and/or interindividual differences in
      biotransformation and excretion rate for these compounds.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1399020
TI  - Absence of blue-yellow color vision loss among workers exposed to toluene or
      tetrachloroethylene, mostly at levels below occupational exposure limits.
AB  - Possible color vision loss was examined with Lanthony's new color test and
      Ishihara's color vision test in 261 solvent workers and 120 controls (48 men and
      72 women). The solvent workers were exposed to either predominantly toluene [46
      ppm as geometric mean (GM); 63 men and 111 women], tetrachloroethylene alone (13
      ppm; 30 men and 34 women), or a mixture (14 men and 9 women) of
      tetrachloroethylene (12 ppm) and trichloroethylene (7 ppm). The only instances of
      color vision loss that were detected in either the exposed workers or the
      controls were six cases of red-green loss (all in men). These six cases of red
      green loss showed an unbiased distribution between the exposed workers and the
      nonexposed controls.

PMID- 1399022
TI  - Shiftwork: its impact on the length and quality of sleep among nurses of the
      Valencian region in Spain.
AB  - Previous research has shown the repercussions of shiftwork for workers' sleep.
      The objective of the present work is to evaluate the impact of shiftwork on the
      length and quality of sleep among nurses and on the intake of psychotropic drugs.
      A cross-sectional epidemiological study was carried out in 606 female nurses and
      367 male nurses selected at random from the public hospitals in the Valencian
      region. Information was collected by means of a questionnaire. Univariate and
      multivariate statistical analysis techniques were used. For both female and male
      nurses, shiftwork led to a reduction in the length of sleep (by 2 h in those
      permanently on night shifts and by 30 min in those on a rotating night shift
      system) and an alteration in the quality of sleep (difficulty in sleeping,
      intermittent sleep, early waking, etc. occurred 10% more frequently), but it did
      not lead to an increase in the consumption of psychotropic drugs.

PMID- 1399021
TI  - Detection of carbon disulfide in breath and air: a possible new risk factor for
      coronary artery disease.
AB  - Carbon disulfide (CS2) is toxic to the heart and arteries; chronic exposure can
      result in accelerated atherosclerosis and coronary artery disease in humans and
      animals. Exposure to CS2 was investigated in normal volunteers working in New
      York City, using a new and highly sensitive assay. Volatile organic compounds in
      breath and air were captured in adsorbent traps containing graphitized carbon and
      molecular sieve, then thermally desorbed, concentrated by two-stage cryofocusing,
      and assayed for CS2 by gas chromatography/mass spectroscopy. Breath CS2 assays
      were performed in 42 normal volunteers, as well as in room air and in outdoor air
      collected at sites in and around New York City. The assay was linear,
      reproducible, and sensitive to picomolar (10(-12) mol/l) quantities. CS2 was
      detected in all samples of breath and indoor and outdoor air (mean concentrations
      were 5.25 pmol/l, SD = 3.89 in breath, 8.26 pmol/l in indoor air, and 3.92 pmol/l
      in outdoor air) (NS). The alveolar CS2 gradient (alveolar-inspired CS2) ranged
      from -20.0 to 8.0 nmol/l, separating subjects into either "excreters" or
      "retainers" of CS2. In view of the known toxicity of CS2, atmospheric pollution
      with CS2 merits attention as a possible new risk factor for the development of
      accelerated atherosclerosis and coronary artery disease.

PMID- 1399023
TI  - Aptitude for physical exercise in a population of female hospital workers.
AB  - The aim of this study was to evaluate the level of physical capacity in a female
      hospital population of Paris and its suburbs. A total of 1505 women working in
      the selected departments filled in a questionnaire concerning their working
      conditions, life habits and health and also attended a medical examination. The
      effort test performed consisted in flexing the legs 20 times with the chest held
      straight, in 40 s. The heart rates were measured for the first, the second and
      the third minutes of recovery (first 15 s multiplied by 4). The blood pressure
      was measured just after the heart rate, for the first and the third minute.
      Recovery indices have been constituted from the results. The respective weights
      of anthropometric and sociodemographic risk factors for recovery indices were
      studied in multiple logistic regression models. The classification enables us to
      consider about 25%-30% of our population as having a satisfactory physical
      capacity, about 26%-27% as having an acceptable capacity, and about 24%-27% as
      having a weak capacity. About 21% of the population presented an excessive
      pressure reaction and 44% a questionable pressure reaction. Our results
      concerning the level of physical capacity of the female nursing staff should be
      taken into account especially in the future planning of work loads and
      architectural choices, which must avoid excessive physical burdens in relation to
      this level. An improvement in the level of physical capacity could be envisaged
      as well.

PMID- 1399024
TI  - Clinical studies in workers engaged in maintenance of watermark moulds in a paper
      mill.
AB  - Thirty subjects engaged in maintenance and repair of moulds used for producing
      watermarks on paper were studied, along with 27 control subjects from the same
      paper mill. The workers were simultaneously exposed to copper, chromium, zinc,
      xylol, and fumes of sulphuric acid in the course of their work. The study
      subjects were investigated for clinical, occupational, radiological
      haematological and psychological details. The aforementioned combined exposure
      was found to be responsible for a high prevalence of symptoms pertaining to the
      respiratory system and higher nervous functions. Breathlessness (26.7%),
      expectoration (10.0%) and emphysema (10.0%) were significantly higher among the
      exposed subjects. The exposed subjects also showed lowered visuomotor
      coordination and delayed reaction to light and sound stimuli.

PMID- 1399025
TI  - Rheological and immunological findings in dockers with vibration-induced white
      fingers.
AB  - The aim of the present study was to characterize rheological and immunological
      features involved in the pathogenesis of vibration-induced white fingers (VWF).
      Plasma viscosity, at two shear rates (580 s-1 and 1164 s-1), levels of
      immunoglobulins (IgG, IgM, IgA), circulating immune complexes, rheumatoid factor,
      antinuclear antibodies, fibronectin, fibrinogen, hemoglobin and erythrocyte
      sedimentation rate were analysed in 30 male dockers with VWF and in 30 healthy
      male referents unexposed for hand-arm vibrations. Decreased plasma viscosity was
      observed among the men with VWF, although formal significance (P less than 0.05)
      was only obtained at shear rate 580 s-1. The decrease was mainly seen among
      smokers. In the study there were no significant differences between the VWF group
      and the referents with regard to immunoglobulin levels, autoantibodies and other
      plasma proteins. From the study it is concluded that workers with VWF may have a
      decreased plasma viscosity. The biological relevance of this observation is
      uncertain and deserves further study.

PMID- 1399026
TI  - Stereometabolism of ethylbenzene in man: gas chromatographic determination of
      urinary excreted mandelic acid enantiomers and phenylglyoxylic acid and their
      relation to the height of occupational exposure.
AB  - Ethylbenzene is an important industrial solvent and a key substance in styrene
      production. Ethylbenzene metabolism leads to the formation of mandelic acid,
      which occurs in two enantiomeric forms, and phenylglyoxylic acid. To decide which
      enantiomer is preferably formed, 70 urine samples of exposed workers were taken
      at the end of shifts and--after 3-pentyl ester derivatisation--gas
      chromatographically analysed. The R/S ratio of mandelic acid enantiomers in urine
      amounts to 19:1, which means that R-mandelic acid is a major metabolite and S
      mandelic acid is one of the minor urinary metabolites of ethylbenzene in man. The
      R/S ratio is independent of ambient air concentration of ethylbenzene within the
      investigated range. Compared to an ethylbenzene monoexposure the height of total
      mandelic acid excretion is decreased in the case of coexposure to other aromatic
      solvents.

PMID- 1399027
TI  - Percutaneous absorption of N,N-dimethylformamide in humans.
AB  - Skin penetration fo N,N-dimethylformamide (DMF) liquid or vapour was studied in
      volunteers. Exposure to liquid DMF was performed in two ways: in a "dipping
      experiment", one hand was dipped up to the wrist in DMF for 2-20 min, while in a
      "patch experiment", 2 mmol DMF was applied to the skin and allowed to be absorbed
      completely. The period of exposure to DMF vapour (50 mg.m-3) was 4 h. The DMF
      metabolites N-hydroxymethyl-N-methylformamide ("MF"), N-hydroxymethylformamide
      ("F"), and N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) were monitored in the
      urine. Liquid DMF was absorbed through the skin at a rate of 9.4 mg.cm-2.h-1.
      Percutaneous absorption of DMF vapour depended strongly on ambient temperature
      and humidity and accounted for 13%-36% of totally excreted "MF". The results
      suggest that skin absorption of liquid DMF is likely to contribute to
      occupational exposure substantially more than penetration of DMF vapour. The
      yield of metabolites after transdermal DMF absorption was only half of that seen
      after pulmonary absorption. Elimination of "MF" and "F" but not that of AMCC was
      delayed, which supports the contention that AMCC should be used instead of "MF"
      as the most suitable biomarker of DMF in cases where percutaneous intake can
      occur.

PMID- 1399028
TI  - Absorption, metabolism and elimination of N,N-dimethylformamide in humans.
AB  - Excretion of N,N-dimethylformamide (DMF) and DMF metabolites N-hydroxymethyl-N
      methylformamide ("MF"), N-hydroxymethyl-formamide ("F") and N-acetyl-S-(N
      methylcarbamoyl)cysteine (AMCC) has been monitored in the urine of volunteers
      during and after their 8-h exposure to DMF vapour at a concentration of 10, 30
      and 60 mg.m-3. The pulmonary ventilation in these experiments was typically about
      10 l.min-1 and the retention in the respiratory tract was 90%. After exposure to
      30mg DMF.m-3, the yield of compound determined in the urine represented 0.3%
      (DMF), 22.3% ("MF"), 13.2% ("F") and 13.4% (AMCC) of the dose absorbed via the
      respiratory tract. The excretion curves of the particular compounds attained
      their maximum 6-8h (DMF), 6-8h ("MF"), 8-14h ("F") and 24-34h (AMCC) after the
      start of the exposure. The half-times of excretion were approximately 2, 4, 7 and
      23 h respectively. In contrast to slow elimination of AMCC after exposure to DMF,
      AMCC was eliminated rapidly after AMCC intake. This discrepancy could be
      explained by rate-limiting reversible protein binding of a reactive metabolic
      intermediate of DMF, possibly methylisocyanate.

PMID- 1399029
TI  - Hand-arm vibration syndrome and its prevalence in the present status of private
      forestry enterprises in Japan.
AB  - Currently there are no limitations on age of employment on private forestries in
      Japan. Hence, it was hypothesized that in these kind of enterprises, elderly
      chain saw operators, or those with long-term exposure, might be at higher risk of
      developing hand-arm vibration syndrome (HAVS). We consequently investigated the
      prevalence of HAVS in 447 chain saw workers on private forestries in Gifu
      Prefecture, Japan, with particular reference to age and exposure period. Of this
      population, 43 (9.6%) had signs and symptoms of vibration-induced white finger
      (VWF), and among these workers the severity of finger blanching was significantly
      correlated (P less than 0.01) with the exposure period. Classification of all
      subjects by exposure period showed that workers with greater than or equal to 30
      years' exposure had higher prevalences of VWF (20.9%) and numbness of the hands
      (25.4%) compared to other groups. Significant differences (P less than 0.01) were
      found between the functional capacities of workers with VWF and those of control
      subjects. We concluded that (a) the elderly chain saw operators and those with
      longer exposure should be moved to other jobs with a lower or no risk of exposure
      to vibration, and (b) the results of screening tests, even without cold water
      immersion (which we did not employ, in order to protect workers' hands), could be
      helpful for the identification of workers with VWF.

PMID- 1399030
TI  - Reference values for blood benzene in the occupationally unexposed general
      population.
AB  - Blood benzene was determined by gas chromatography-mass spectrometry in 431
      "normal" subjects, subdivided into 155 rural subjects and 276 urban subjects.
      Blood benzene (mean value 262 ng/l) was significantly lower in rural (200 ng/l)
      than in urban (296 ng/l) workers, as well as differing significantly between 293
      non-smokers and 138 smokers (205 ng/l and 381 ng/l, respectively). Among non
      smokers, values were significantly higher (307 ng/l) in 76 chemical workers. In
      the total study population, in 95% of cases blood benzene was less than 718 ng/l,
      the 95th percentile being 514 ng/l in non-smokers vs 901 ng/l in smokers and 576
      ng/l in rural vs 822 ng/l in urban subjects. Within each population subgroup, the
      difference between non-smokers and smokers was statistically significant, except
      among office workers (non-smokers 234 ng/l, smokers 304 ng/l). Blood benzene (y)
      was directly proportional to the number of cigarettes smoked (x) (y = 201 + 12x;
      r = 0.44; n = 431), and inversely proportional to the interval between the last
      cigarette and the time at which the blood samples was taken (z) (log y = 6.167
      0.0015z; r = -0.461; n = 135). The blood half-life of benzene was about 8h. The
      multiple correlation between blood benzene (Cb), number of cigarettes per day (x)
      and time since the last cigarette (z) is: Cb = 417 + 7.2x - 0.41z (n = 135; R =
      0.20; P less than 0.00001).

PMID- 1399031
TI  - Insect hemoglobins (Chi tI) of the diptera family Chironomidae are relevant
      environmental, occupational, and hobby-related allergens.
AB  - Six hundred and forty-two persons with hobby-related (n = 205), occupational (n =
      85), or environmental contact (n = 352) to the midge and larval allergen Chi tI
      were studied. Frequencies of IgE-mediated sensitization in these selected
      populations were 36.1%, 24.7%, and 9.6% respectively. Occupationally sensitized
      subjects who had been heavily exposed showed higher levels of antibodies, were
      more frequently diagnosed as having bronchial asthma and less frequently as
      having conjunctivitis, and had a significantly shorter latency period when
      compared to environmentally exposed people or aquarists. Our results are evidence
      for a higher risk of sensitization and of bronchial asthma in highly exposed
      subjects.

PMID- 1399032
TI  - Decreased excretion of thioethers in urine of smokers after the use of beta
      carotene.
AB  - Epidemiologic studies have demonstrated an inverse relation between vitamin A
      intake and lung cancer rate. There is strong evidence that the provitamin A, beta
      carotene, plays a more important role in the protective effect than vitamin A
      itself. The anticarcinogenic properties of beta-carotene have so far been
      attributed to its scavenger properties in deactivating or trapping reactive
      chemical species such as singlet oxygen and certain organic free radicals.
      Smoking results in increased excretion of detoxification products of
      electrophilic agents (mercapturic acids) in urine. Since reactive electrophilic
      intermediates are involved in carcinogenesis, we performed a double-blind,
      placebo-controlled intervention trial to investigate whether the intake of beta
      carotene by smokers would affect urinary thioether excretion. Before the
      intervention the beta-carotene group (n = 62) and the placebo group (n = 61) had
      similar thioether excretion levels in urine (4.2 vs 4.3 mmolSH/mol creatinine).
      During the intervention (20 mg beta-carotene daily for 14 weeks) the placebo
      group showed a 12% increase, whereas the beta-carotene group showed a 5% decrease
      (P = 0.004). After the intervention the beta-carotene group had a 15% lower
      thioether excretion level than the placebo group (4.1 vs 4.7 mmolSH/mol
      creatinine; P = 0.0017). Our study shows that urinary thioether excretion varies
      considerably over time, and that smokers have a decreased excretion of thioethers
      in urine after the use of beta-carotene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399033
TI  - Role of occupational exposure to airway irritants in the development of asthma.
AB  - In order to study the role of occupational exposure in the etiology of asthma, 78
      asthmatics and 56 nonasthmatics from the Finnish twin cohort were investigated by
      means of a postal questionnaire. Among those studied were 31 identical twin pairs
      discordant with regard to asthma (i.e., only one member of the pair had asthma).
      The questionnaire inquired into the diagnosis and status of the asthma, smoking
      habits, atopic background, smoking history of the parents, and history as regards
      pets, and requested a detailed description of occupational exposure to airway
      allergens and irritants. Classification into asthmatics and nonasthmatics was
      based on the information gathered with the questionnaire, supplemented by other
      information whenever possible. Estimation of exposure was based on the subject's
      own report, on the work descriptions, and on the general knowledge about the
      exposure levels associated with work tasks in question. Exposure to organic
      solvents was found only in the asthmatic members of the discordant pairs, and
      none of the nonasthmatic persons had been exposed to solvents. There were no
      statistically significant differences as regards exposure to other unspecific
      irritants. Combined exposure to organic allergens and airway irritants was more
      common in the asthmatics than in the nonasthmatics (P = 0.009). Exposure to
      irritants was also more common among the asthmatics than the nonasthmatics with
      similar exposure to organic allergens (P = 0.004).

PMID- 1399035
TI  - Porcelain laminate veneers with three-dimensional shade reproduction.
AB  - A new system for creating porcelain veneers with three-dimensional shade options
      is described. The development of a new porcelain consisting of an intense colour
      which provides natural tooth aesthetics in layers of only 0.5 mm has made the
      system possible. In addition a masking porcelain may be used over discoloured
      tooth tissue. The new system is claimed to supersede the sometimes less aesthetic
      shades created with other laminate systems, as well as enhancing the marginal
      integrity of the veneer.

PMID- 1399036
TI  - Saliva and dental caries: diagnostic tests for normal dental practice.
AB  - Salivary diagnostics is now entering the surgery of the modern dentist, although
      no test yet available is so specific and sensitive that caries can be diagnosed
      from saliva samples only. The present tests are useful for estimating the caries
      activity due to bad dietary habits (salivary lactobacilli), establishing the
      presence of infection (salivary mutans streptococci), and identification of
      salivary yeasts for the determination of the medical condition of the patient.
      Buffer capacity reveals the most important host response factor acting against
      caries, while measures of flow rate form the diagnostic basis for treatment
      planning. These tests, alone or in combination, are now so easy to perform that
      they should be used in every dental practice.

PMID- 1399034
TI  - Chromosome aberrations and micronuclei in lymphocytes of workers exposed to low
      and medium levels of styrene.
AB  - In the present study we analysed 19 workers exposed to styrene in two factories
      where polyester resins were used. Because of the different sizes of the pieces
      undergoing resin processing, the environmental styrene concentrations and urinary
      mandelic acid (MA) levels of the analysed subjects were quite different in the
      two plants examined. Cytogenetic monitoring was performed by analysis of
      chromosome aberrations (CAs) and micronuclei (Mn) in peripheral blood
      lymphocytes. Cytogenetic analysis revealed a significant increase in the
      percentage of aberrant cells and total aberrations in the group with higher
      styrene exposure (group 2) and no increase in the group with lower exposure
      (group 1), as compared with matched controls. Mn frequencies were not
      significantly increased in the two exposed populations. No correlations between
      length of exposure and CA or Mn frequency were found, and a weak correlation was
      found between exposure levels, measured as urinary MA, and Mn frequencies. Only 5
      of the 12 exposed workers examined in group 2 had urinary MA levels higher than
      the limit recommended by the ACGIH in 1990-91 [1]. Significant increases in DNA
      damage are therefore already found at urinary MA levels lower than the
      internationally suggested exposure limits.

PMID- 1399037
TI  - Is there a need for gerodontology?
AB  - One of the major criteria of successful ageing is maintaining a natural, healthy,
      functional dentition throughout life, including all the social and biological
      benefits such as aesthetics and comfort, and the ability to chew, taste and
      speak. However, the oral health of elderly people is far from optimal. The
      treatment needs are high due to edentulism, missing teeth, caries, periodontal
      diseases and tooth wear resulting in impaired oral functions. The demand for
      treatment is much lower than the need. In the future the elderly will retain
      their natural dentition and more teeth per individual will be present. Despite
      this there will be a rise in edentulousness due to the sharp rise in numbers of
      the elderly population. The 'new elderly' will be more critical and more
      demanding of oral health care services. The dental profession and governments in
      all industrialised countries must be aware of these trends which should be
      reflected in undergraduate and postgraduate education of dentists and in
      research. The European College of Gerodontology has been founded to contribute to
      solving all problems related to oral health and oral health care of the elderly.

PMID- 1399038
TI  - A comparison of patients' perception of dental care offered by male or female
      dentists in New Zealand.
AB  - Recent increases in women dentists in New Zealand follow similar trends in other
      Western countries. The career patterns of female dentists, and male dentists'
      attitudes towards women dentists in New Zealand have been previously studied. The
      aim of this study was to compare the attitudes and preferences of patients
      towards dental care offered by either male or female dentists, to determine what
      influences these preferences, and to discover whether or not these opinions
      differed between regular or irregular attenders.

PMID- 1399039
TI  - The role of the dental team in promoting dental health and general health through
      oral health.
AB  - The two major dental diseases are related to diet and dirt. These are common risk
      factors for a number of chronic diseases. A logical approach to the prevention of
      chronic diseases is to focus on risk factors rather than on specific diseases, a
      common risk factor approach using health promotion. Health promotion is the
      process of enabling individuals and communities to increase control over the
      determinants of health and thereby improve their health. The concepts
      incorporated in health promotion include a promotion of health through public
      policy, creating supportive environments, developing personal skills,
      strengthening community action and reorienting health services. The dental team
      should incorporate the following principles: integration with general health
      education, encouraging participation of the community, the public and staff in
      the planning process; making healthy choices the easier choices. By adopting a
      Common Risk Factor Strategy incorporated into Primary Health Care, dental teams
      can promote dental health and general health. The latter objective will be
      achieved by reducing pain and suffering related to dental diseases. A much
      broader remit for dental teams is outlined, one which will do justice to the
      abilities and training of all members of the team.

PMID- 1399040
TI  - Disturbances caused by dental materials in magnetic resonance imaging.
AB  - Nuclear Magnetic Resonance (NMR) is the latest addition to medical imaging
      technology. This technique plays an important role in head and neck diagnosis.
      Radiologists may encounter patients with fixed dental prostheses that may produce
      image distortion on MRI scans of the face. The MRI appearances of dental
      prosthetic materials was studied in vitro, including precious alloys, non
      precious alloys, ceramic prostheses, dental amalgam and composite materials. It
      was found that non-precious alloys produce large image deformations, whereas
      precious alloys had no effect on MRI images. An in vivo study showed the
      anatomical zones that were most affected on MRI scans.

PMID- 1399041
TI  - Racial differences in perception of oral health and oral health behaviours in
      Singapore.
AB  - Knowledge of prevention can influence preventive dental behaviours. This study
      surveyed knowledge and preventive dental behaviours on the prevention of dental
      caries and gum disease among the adult population of the three major racial
      groups in Singapore. Respondents were asked to rate the importance of several
      preventive measures against dental caries and gum disease. Questions were also
      fielded on dental behaviours such as preventive visits to the dentist,
      toothbrushing and flossing. Results showed that there was a general lack of
      appreciation for the use of flossing, dental sealants and fluoride supplements.
      Although a majority of respondents thought that regular dental checkups would be
      essential for prevention, the proportion who actually saw the dentist for
      preventive care was significantly lower. Respondents provided inappropriate
      reasons for brushing their teeth. Differences in both preventive knowledge and
      preventive dental behaviours among racial groups were evident although these were
      attributed to differences in education and exposure to product information rather
      than to racial or cultural factors.

PMID- 1399042
TI  - Disinfection and sterilisation: the duties and responsibilities of dentists and
      dental hygienists.
AB  - Disinfection and sterilisation have received a considerable amount of attention
      due to the spread of AIDS in the past few years. There appears to be a low risk
      of occupational transmission of HIV, but this is not the case with other
      transmissible diseases. There are about 40 infection hazards for the patient and
      dental personnel in the dental surgery. Disinfection and cleaning are important
      in disease containment and cross-infection control, and all members of the dental
      team must bear responsibility for this. Disinfection of hands, surfaces,
      instruments, impression materials, radiographic units and suction systems are
      discussed. In addition, sterilisation and hygiene management of the reception
      area are considered. The duties and responsibilities of the dental team are
      emphasised.

PMID- 1399043
TI  - Symposium. Chemotherapeutic mouthrinses for the control of oral diseases.

PMID- 1399044
TI  - Rinses for the control of dental caries.
AB  - Fluoride mouthrinsing at two different strengths and two different rinse
      frequencies has proven a versatile method of caries control for individual home
      based programmes and community school-based programmes. An advantage of
      mouthrinsing is that the vehicle is not complex and does not interfere with the
      intraoral distribution of fluoride ions to caries predilection sites. An average
      caries reduction of about 30 per cent can be expected from use of this method.
      The percentage caries reduction, which is a relative figure, is considered to be
      a property that is intrinsic to the preventive regimen itself, in this case
      fluoride mouthrinsing, and is unaffected by the caries attack rate of the
      population being served. On the other hand, the benefit of the procedure is a
      function of the numerical caries reduction achieved by the intervention.
      Numerical reductions are absolute figures which do depend upon the caries rate of
      the population. High caries attack rates increase the numerical caries reduction
      because there are more lesions to inhibit; low attack rates produce low numerical
      reductions and consequently low benefits. Therefore, the decision to use fluoride
      mouthrinsing for either an individual or a community must be based upon knowledge
      of the caries risk of the targeted individual or group.

PMID- 1399045
TI  - Rinses to control plaque and gingivitis.
AB  - The dental profession and the public have two different perceptions when it comes
      to oral hygiene. The profession has oral health as its main objective whereas the
      public is more concerned with personal cleanliness and social acceptability.
      Nevertheless the desired outcome is the same, namely to remove supragingival
      plaque. The concept of using a mouthrinse as an adjunct to brushing with a
      dentifrice is a sound one. In recent years there has been a rapid increase in the
      use of mouthrinses and this review considers the relative merits of those
      currently on the market. It is evident that some progress has been made in
      satisfying the priorities of the consumer and clinician.

PMID- 1399046
TI  - Subgingival irrigation systems for the control of oral infections.
AB  - The use of subgingival irrigation systems for the control of oral infections is
      an attractive possibility. The main advantage would seem to be that it would
      provide a means of delivering therapeutic agents to sites otherwise inaccessible
      to the effects of mouthrinses. Much research has therefore concentrated on the
      methods of delivery and the agents so delivered. The effects of various trials on
      individuals with good and poor oral hygiene and using a variety of different
      agents is reviewed.

PMID- 1399047
TI  - Saliva: its role in health and disease. Working Group 10 of the Commission on
      Oral Health, Research and Epidemiology (CORE)

PMID- 1399048
TI  - Microbiological evaluation of the efficacy of chlorhexidine in a sustained
      release device for dentine sterilization.
AB  - The aim of this in-vitro study was to evaluate the effect of chlorhexidine in
      solution and in a sustained-release device as an intracanal medication. Hollow
      cylindrical dentine specimens prepared from bovine incisors were incubated with
      Streptococcus faecalis for a period of 3 weeks. The intracanal medicaments tested
      were 0.2% chlorhexidine gluconate solution (CH), chlorhexidine in a sustained
      release device (1.2 mg) (SBD), camphorated paramonochlorophenol (CMCP), and a
      control (no medication). Each medicament was introduced into the lumen of one
      dentine specimen and incubated for 5 min, 24 h, 48 h or 7 days at 37 degrees C.
      The bacteriological samples were taken by shaving the dentine inside the lumen
      with dental burs ranging in size from ISO 023-033. The dentine powder was
      collected in test-tubes containing growth medium and incubated for 24 h. The
      optical density of the medium was recorded by means of a spectrophotometer at a
      wavelength of 540 nm. There was a statistically significant difference between
      the control group and all the medicaments tested.

PMID- 1399049
TI  - Bacterial invasion of non-exposed dental pulp.
AB  - Anaerobic procedures were adopted to demonstrate the early bacterial invasion of
      non-exposed dental pulps, and to isolate and identify the bacteria. Of 19 freshly
      extracted teeth which originally exhibited deep dentinal lesions, clinical
      examination and electric pulp testing showed that nine of them had no pulpal
      exposure. Thus the pulps of these teeth were covered by clinically sound dentine
      beneath the carious lesion. Bacteria were found to have invaded the pulps of six
      of these nine teeth. The predominant bacteria were obligate anaerobes belonging
      to the genera Eubacterium, Propionibacterium and Actinomyces. Other obligate
      anaerobes were Lactobacillus, Peptostreptococcus, Veillonella and Streptococcus.
      The bacterial composition resembled that of the deep layers of dentinal lesions
      described previously, suggesting that the bacteria isolated in this study had
      passed through some individual dentinal tubules, to invade the dental pulp.

PMID- 1399050
TI  - Efficacy of a sustained-release device containing chlorhexidine and Ca(OH)2 in
      preventing secondary infection of dentinal tubules.
AB  - This study was conducted to evaluate the efficacy of the antibacterial activity
      of Ca(OH)2 and a sustained-release device containing chlorhexidine (SRD) in both
      sterilization and prevention of secondary infection of the root canal system.
      Bovine root dentine specimens previously incubated with Streptococcus faecalis
      were used in this experiment. Two different formulations of the SRD (differing in
      their cross-linkage), Ca(OH)2 and normal saline (control) were evaluated. The
      degree of bacterial infection of the root canal was tested after incubation
      periods of 24 h, 72 h and 7 days with these medicaments. Their efficacy in
      preventing secondary infection after recontamination was tested after 72 h and 7
      days. The results demonstrated that both formulations of the SRD significantly
      reduced the bacterial population in the primary infected groups, as well as
      preventing secondary infection of the dentinal tubules in the recontaminated
      group. By contrast, Ca(OH)2 did not show any antibacterial activity, and failed
      to sterilize the dentinal tubules or prevent secondary infection after
      recontamination at the time periods examined.

PMID- 1399051
TI  - A survey of endodontic procedures performed by practitioners in limited practice.
AB  - Patients are sometimes referred for treatment to dentists who limit their
      practices to endodontics. A survey of consecutive referrals to seven such
      dentists was undertaken. The most common reasons for such referrals were (i) for
      the retreatment of a tooth with a previous root filling, (ii) because the
      referring dentist was unable to control pain and/or swelling, or (iii) because
      the referring dentist was unable to diagnose the endodontic problem. Only 60
      (12.8%) of the 469 reasons reviewed were in teeth that were symptomless,
      uncomplicated and untouched by the referring dentist.

PMID- 1399052
TI  - Dentine-removing characteristics of K-files energized by the Piezon-Endo.
AB  - This in-vitro study evaluated the pattern of dentine removal when a size 25 K
      file energized by the Piezon-Endo was applied to flat surfaces of dentine under
      standardized conditions. The effects of power setting, interfacial force between
      file and dentine, direction of file oscillation and operator-assisted movement
      were examined. Vinyl polysiloxane impressions of the instrumented surfaces
      revealed characteristic patterns consisting of a series of oblique crests,
      similar to those observed in a previous study using the Cavi-Endo. Each crest was
      parallel to the next and separated by a relatively constant distance. These
      crests were disposed along the line of contact with the file. The Reflex
      microscope was used to determine the height, width and separation of these
      crests. There were differences in the amount and pattern of dentine removal
      compared with the study on the Cavi-Endo. When the file was held against the
      dentine surface using the minimum power setting and an interfacial force of 30 g,
      the pattern of dentine removal was very similar to that produced by the Cavi
      Endo. Increasing the power setting to the maximum recommended for endodontics
      produced a slight but statistically non-significant increase in dentine removal.
      Further increase of the power setting to the absolute maximum produced
      significantly deeper and wider areas of dentine removal by the apical part of the
      file.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399053
TI  - Diagnostic dilemma: an unusual presentation of an infected nasopalatine duct
      cyst.
AB  - The pertinent literature on nasopalatine duct cysts is reviewed. A case is
      reported in which a nasopalatine duct cyst infected by Actinomyces presented
      clinically with unusual features. The clinical findings could have been confused
      with an early acute periapical abscess arising from an incisor tooth. The
      relevant aspects of diagnosis are discussed.

PMID- 1399054
TI  - Comparison of six files to prepare simulated root canals. 1.
AB  - A total of 300 simulated root canals of various angles and positions of curvature
      in clear resin blocks were prepared by hand using either K-files, K-Flex files,
      Flexofiles, Flex-R files, Hedstrom files or Unifiles. Each file type was used to
      prepare 50 canals employing a linear filing motion and an anticurvature stepback
      technique. Part 1 of this two-part report describes the efficacy of the files in
      terms of preparation time, instrument failure, loss of canal length and weight
      loss from the blocks. Two-way analysis of variance confirmed that there was
      significant variation for each parameter between instruments, between canal
      types, and with interaction between instruments and canal types. Overall,
      preparation with Hedstrom files was significantly quicker than with any other
      file, whilst preparation with K-files and K-Flex files took significantly longer.
      Fracture and deformation of instruments occurred substantially less often with
      Flex-R and Hedstrom files, but significantly more often with Unifiles. Loss of
      working distance occurred with all file types, but was significantly greater in
      canals prepared with K-files. Unifiles and Hedstrom files were responsible for
      significantly more weight loss than the other files, whilst K-files produced
      significantly less weight loss. Canals with rough undulating walls were created
      most often by Hedstrom files and Unifiles. Overall, under the conditions of this
      study, Flexofiles, Flex-R files and Hedstrom files appeared to be substantially
      more effective than K-files, K-Flex files and Unifiles.

PMID- 1399055
TI  - Comparison of six files to prepare simulated root canals. 2.
AB  - A total of 300 simulated root canals of various angles and positions of curvature
      in clear resin blocks were prepared by hand using either K-files, K-Flex files,
      Flexofiles, Flex-R files, Hedstrom files or Unifiles. Each file type was used to
      prepare 50 canals employing a linear filing motion and an anticurvature stepback
      technique. Part 2 of this two-part report describes the efficacy of the files in
      terms of the prevalence of canal aberrations, the amount and direction of canal
      transportation and the overall postoperative canal shape. Hourglass shaped canals
      were found in 4.5% of curved canals, the majority of these being created by K
      files and K-Flex files. Perforations were seen in 6.3% of curved canals, the
      majority being produced by Flex-R files and K-files. Excessive removal of
      material from along the inner aspect of the canal curve occurred in 10.4% of
      canals, by far the majority being created by Hedstrom files. Transportation of
      canals was a consistent finding with all instruments. Two-way analysis of
      variance revealed how significant differences in the absolute magnitude of
      transportation occurred between instruments, between canal types and by an
      interaction between instrument and canal type. In general, transportation was
      towards the outer aspect of the canal curve at the end-point of preparation and
      the zip and elbow, but towards the inner aspect at the beginning of the curve.
      Further towards the orifice, transportation reverted to the outer aspect of the
      canal curve.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399057
TI  - Variables affecting electronic root canal measurement.
AB  - This study was conducted in two parts. In the first part, 20 single-rooted teeth
      that had been scheduled for extraction were investigated. The electronic root
      canal lengths were measured in vivo with a Dental Sono-Explorer type Y-III, and
      the actual canal lengths were measured after extraction of the teeth. The rate of
      agreement of the two measurements was 77.5% within a range of +/- 0.5 mm, while
      it was 100% at +/- 2.0 mm, which is acceptable clinically. In the second part,
      there were 19 simulated canals whose lengths and apical foramen sizes were known
      beforehand. Experiments revealed a negative correlation between the areas of the
      apical foramina and the difference between the electronic and the actual root
      canal lengths. This relationship was shown by the linear regression equation: y =
      0.6-1.6x. With the exception of the smallest areas of foramina, electronic root
      canal length measurements were less than the actual lengths.

PMID- 1399056
TI  - Blood flow changes in the dental pulp during limited exercise measured by laser
      Doppler flowmetry.
AB  - The effect of limited exercise on pulpal blood flow was assessed by laser Doppler
      flowmetry (LDF). The primary aim of the investigation was to determine whether
      clinically significant changes could be induced by mild exercise when LDF was
      used to monitor pulpal blood flow. Blood flow readings were obtained from the
      coronal pulps of 17 upper central incisor teeth of 10 human volunteers before,
      during and after limited exercise. Readings were also obtained from the adjacent
      attached gingivae. Pulse rate was recorded concurrently. Pulpal blood flow was
      found to vary during exercise, with a mean percentage change of 38% from the
      level at rest; the range was from a 100% decrease to a 200% increase. The mean
      percentage increase in gingival blood flow was 65%, with a range of 6-300%. The
      main indication that blood flow was being assessed was the pulsatile nature of
      the output. Results were compared only within individual teeth. The pulse rate
      increased during exercise (mean percentage increase 54%, range 11-98%). There was
      no direct relationship between increased pulse rate and pulpal blood flow. It was
      evident that the mechanisms controlling pulpal and gingival blood flows differed.
      Laser Doppler flowmetry readings were only reproducible in individual teeth
      provided that the patient was at rest, and this should be taken into account in
      clinical or research measurements.

PMID- 1399058
TI  - A method for experimental dental radiography.
AB  - An apparatus was designed for experimental dental radiography, which permitted
      separate adjustment of the subject, target and film. The precision of the
      apparatus was tested by radiographing a test subject, consisting of small steel
      globes embedded in a plastic plate. The subject was placed in the apparatus and
      exposed 30 times on dental X-ray film with different adjustments of angles and
      distances. All exposures were repeated after readjustment of the same form. Three
      linear distances between pairs of the projected steel globes were selected and
      measured on each radiograph. Depending on the different orientations of film,
      target and subject, the distances measured ranged from 9.0-11.1 mm, from 7.0-10.7
      mm and from 12.7-17.3 mm, respectively. From the measurements on the radiographs
      the error of method was calculated to be 0.07-0.08 mm and the error of
      measurement to be 0.05-0.06 mm. The precision of the apparatus was thus found to
      be adequate for measurement of differences in small, but clinically relevant,
      distances.

PMID- 1399059
TI  - The role of intracanal medication in root canal treatment.
AB  - The role of intracanal medication as a root canal dressing is re-examined. In
      pulpectomy and some root canal treatments, where the root canal contains vital
      pulp tissue, it is doubtful whether a routine intracanal medicament is needed. In
      infected root canals, intracanal medication has been advocated for many purposes.
      An intracanal medicament is used to: (i) eliminate any remaining bacteria after
      canal instrumentation; (ii) reduce inflammation of periapical tissues and pulp
      remnants; (iii) render canal contents inert and neutralize tissue debris; (iv)
      act as a barrier against leakage from the temporary filling; (v) help to dry
      persistently wet canals. However, most of the indications for intracanal
      medicaments are questionable. Intracanal medicaments should only be used for root
      canal disinfection as part of controlled asepsis in infected root canals, and
      their role is secondary to cleaning and shaping of the root canal. Thorough canal
      debridement and adequate canal preparation are more pertinent, and their
      importance is emphasized. Bacteriological sampling may be necessary if a tooth
      does not respond to treatment, to help in the choice of intracanal medicament.

PMID- 1399060
TI  - Failure characteristics of endodontically treated premolars restored with a post
      and direct restorative material.
AB  - Ninety-one extracted maxillary premolar teeth were restored with a prefabricated
      post and amalgam, composite resin or glass-cermet core. Each group was again
      divided into three groups of 9-13 teeth to be subjected to an increasing load in
      one of three standardized directions (10, 45 and 90 degrees to the long axis of
      the tooth). Failure load and characteristics of failure were recorded. The glass
      cermet-restored teeth had a lower strength than the other groups for every load
      direction (Student's t-test: P less than 0.01). Amalgam and composite resin
      groups showed a significant difference only for the 10 degrees loading condition
      (Student's t-test: P less than 0.02). Teeth restored with amalgam cores displayed
      a higher mean failure load, in combination with a 46% occurrence of root
      fracture.

PMID- 1399061
TI  - The physical properties of a new sealing cement.
AB  - This study was performed on a newly developed sealing cement, TS60, to evaluate
      its physical properties, namely sealing, setting time, compressive strength,
      solubility and ease of removal. It was compared with Temporary Stopping (GC
      Dental Industrial Corp., Tokyo, Japan), Eugedain (zinc oxide-eugenol based
      material, Showa Yakuhin Kako Co. Ltd, Tokyo, Japan) and Cavit-G (calcium sulphate
      based material, Espe Gmbh, Seefeld, Germany), which are typical commercially
      available sealing cements. The results of the study revealed that TS60 had
      excellent sealing properties, good compressive strength, low solubility, and was
      readily removable by heating and melting.

PMID- 1399062
TI  - Pulp responses to two strains of bacteria isolated from human carious dentine (L.
      plantarum) (NCTC 1406) and S. mutans (NCTC 10919).
AB  - A series of studies has been conducted in which monoinfected gnotobiotic rats
      were used to study the responses of the dental pulp to micro-organisms isolated
      from carious lesions in dentine. In this study pulp responses to L. plantarum
      (formerly odontolyticus) (NCTC 1406) in pure culture and in combination with S.
      mutans (NCTC 10919) are reported. The incidence of inflammation/necrosis/dentine
      bridge formation observed in animals monoinfected with L. plantarum was similar
      to that reported in previous germ-free studies. There was a greater incidence of
      dentine bridge formation in rats monoinfected with L. plantarum compared with
      those monoinfected with S. mutans. When the two organisms were combined,
      periapical inflammation was observed in 14% of the teeth examined after 28 days,
      but there was no significant difference in the incidence of dentine bridge
      formation. Considerable variation in the density of staining of the two
      microorganisms in histological sections was observed.

PMID- 1399063
TI  - Pulp response to, and cariogenicity of, a further strain of Streptococcus mutans
      (NCTC 10832).
AB  - The pulpal response to and cariogenicity of a third strain of Streptococcus
      mutans, namely S. mutans (NCTC 10832), was studied in monoinfected gnotobiotic
      rats of the Fischer strain using the techniques described previously by the
      present authors. Unlike S. mutans (NCTC 10449 and 10919), S. mutans (NCTC 10832)
      was associated with the presence of inflammatory cell infiltrates in the coronal
      pulp of a small number of teeth and extensive periapical inflammation 28 days
      after the creation of untreated pulpal exposures. S. mutans (NCTC 10832) was
      associated with the presence of extensive pulpal necrosis and reduced dentine
      bridge formation. These changes were similar to those noted with the other two
      strains of S. mutans. S. mutans (NCTC 10832) was non-cariogenic in monoinfected
      gnotobiotic rats of the Fischer strain.

PMID- 1399064
TI  - Root fractures in permanent teeth: a clinical review.
AB  - A retrospective study of 22 root fractures in 21 patients was performed. Ten
      patients were less than 11 years of age, and boys were involved more often than
      girls. Ten patients had more than one injured tooth, but there was no case of
      alveolar fracture. Twenty-one of the teeth were upper central incisors. Only 11
      teeth were seen within the first week, so that not all teeth were splinted and
      not all displaced teeth were repositioned. Long-term clinical and radiographic
      review showed that loss of vitality of the coronal pulp could not be reliably
      detected for at least 1 year. No tooth became abscessed or developed a sinus
      tract, and resorption of bone at the fracture line was observed in only one out
      of five non-vital teeth. Lack of displacement and placing of a splint increased
      the chances of the pulp remaining vital and healing of the fracture occurring
      with hard tissue. Sclerosis of the coronal pulp occurred mainly when healing was
      by connective tissue. The apical pulp always remained vital, and there was
      sclerosis of the apical pulp in almost every case.

PMID- 1399065
TI  - Asymmetry of the root canal foramen.
AB  - Deviation of the major apical foramen from the anatomical root apex is a
      recognized phenomenon. To determine the frequency, position and mean distance of
      the major apical foramen from the anatomical root apex, 230 roots of permanent
      teeth were examined stereomicroscopically and radiographically. Radiographic
      analysis was used to establish how accurate the conventional radiograph was in
      displaying such a deviation. The frequency of deviation of the major foramen,
      determined stereomicroscopically, was 76%, and depended on the type of teeth
      examined. Radiographic analysis of the same sample revealed 57% of root canals
      had asymmetry of the root canal foramen. Agreement of stereomicroscopic and
      radiographic findings was found to be 61%. The most frequent deviation of the
      major foramen was on the distal root surface (29%), but this was not
      statistically significant. The mean distance between the deviation of the major
      foramen and the anatomical root apex was 0.99 mm. The study indicates that the
      clinician should consider deviation of the foramen during root canal treatment,
      as the deviation could not easily be detected radiographically.

PMID- 1399066
TI  - Garre's osteomyelitis: a case report.
AB  - This is a case report of Garre's osteomyelitis caused by infection from a lower
      left molar which was successfully managed by root treatment following several
      unsuccessful attempts with antibiotic therapy alone. After 18 months there was
      complete resolution of the bony lesion.

PMID- 1399067
TI  - Undergraduate curriculum guidelines for endodontology. European Society of
      Endodontology.

PMID- 1399068
TI  - Quantitative radioactive analysis of microleakage of four different retrograde
      fillings.
AB  - Sealing properties of four different retrograde filling materials were
      investigated in vitro. Radioactive isotopes were applied in the root canal, and
      leakage into an extraradicular fluid was measured at regular intervals. The
      method permitted repeated observation of the specimens over prolonged periods of
      time. Forty single-rooted human teeth were biomechanically instrumented and
      obturated using calcium-hydroxide paste. Following obturation, an apicectomy was
      performed and retrograde cavities were filled with four different materials:
      group 1, non gamma 2 amalgam (Amalcap); group 2, glass ionomer cement (Ketac
      Silver); group 3, calcium-hydroxide-based root canal sealer (Sealapex); group 4,
      composite resin (Palfique Light-S). After removal of the calcium hydroxide, the
      teeth were immersed in a fluid. An isotope solution was then placed in the root
      canals. Samples were taken from the fluid at 0, 3, 7, 28, 56, 105, 210, 285 and
      376 days to determine the radioactivity. It was found that Sealapex and Palfique
      Light-S showed significantly less leakage than amalgam and glass ionomer cement,
      which had the highest apical leakage.

PMID- 1399069
TI  - Systemic release of corticosteroids following intra-dental use.
AB  - Concern has been expressed in the past that the use of corticosteroids within
      root canal medicaments or pulp capping agents may lead to deleterious systemic
      effects. Calculations of the highest possible amounts that could be used, plus an
      analysis of the release and diffusion characteristics, and comparisons with known
      endogenous levels of corticosteroids, reveal that the intradental use of Ledermix
      paste and Ledermix cement is unlikely to result in any systemic side-effects.

PMID- 1399070
TI  - Tissue responses to Hydron, assessed by intraosseous implantation.
AB  - Teflon tubes containing freshly mixed, polymerized Hydron root canal filling
      material, fully set AH26 or Teflon were implanted into the mandible of guinea
      pigs and assessed histologically at 2 days, 1, 2, 4, 12 and 26 weeks. None of the
      materials tested elicited signs of overt or significant tissue damage, and
      polymerized Hydron was assessed to be as biocompatible as fully set AH26 and
      Teflon. Bone formed in very close apposition to the polymerized Hydron, whereas a
      soft tissue capsule separated the regenerated bone from implants of AH26 and
      Teflon.

PMID- 1399071
TI  - Tissue responses to Hydron, assessed by intramuscular implantation.
AB  - Freshly mixed polymerized Hydron root canal filling material, fully set AH26 and
      Teflon were implanted in the quadriceps muscle of guinea pigs and assessed
      histologically at 2 days, 1, 2, 3, 12 and 26 weeks after implantation. All
      materials were characterized by peri-implant fibrous connective tissue capsule
      formation. Von Kossa-positive calcific material was observed at the implant
      tissue interface of Hydron implants. The amount of apparently calcified material
      increased with time. Inflammation was not a prominent tissue response for any of
      the test materials, nor was a foreign body giant cell response.

PMID- 1399072
TI  - Cell responses to Hydron by a new in-vitro method.
AB  - An in-vitro biotoxicity test system, suitable for the assessment of endodontic
      filling materials, has been developed and used to test cell responses to Hydron,
      AH26 and Tubliseal. A robust, well-characterized and stable cell line (L-cells)
      which was grown as uniform cultures on Millipore filters, has been used as
      indicator cells. As they approached confluence they were exposed to test
      substances for 24 h and biosynthetic activities were measured. The test system is
      a modification of that described by Wennberg et al. (1979). By inverting the
      cultures on organ-culture rafts, cells were separated from the test material,
      which was placed on top of the Millipore filters. Freshly mixed polymerizing
      Hydron and prepolymerized Hydron were tested. The cell responses were compared
      with those of cultures exposed to freshly mixed AH26 and Tubliseal. Polymerizing
      and prepolymerized Hydron depressed both cell division, assessed by 3H-thymidine
      incorporation, and the synthesis and secretion of matrix material as measured by
      precipitable 35S-sulphate. Prepolymerized Hydron decreased cell functions by 59%
      and 56% of live cell controls, respectively, while the freshly mixed polymerizing
      Hydron inhibited biosynthesis by 89% and 94%, respectively. The data for
      polymerizing Hydron were compared with results for other root-filling materials
      and showed similar values to those for Tubliseal (92% and 95%), but greater
      inhibition of biosynthesis than for AH26 (53% and 50%). The AH26 values were
      similar to those obtained from cultures exposed to the prepolymerized Hydron.
      Recovery of biosynthetic capacity by these cultures after removal of all
      endodontic material was also assessed. Partial biosynthetic recovery of cell
      cultures was observed 24 h after removal of preopolymerized Hydron.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1399074
TI  - Assessments of social support exchanges: cognitions of the old-old.
AB  - In this study of the old-old, perceptions of thirty-one individuals regarding
      exchanges in their social relationships are explored. Two questions are
      addressed: 1) What cognitive mechanisms are used to assess equity in social
      exchanges? 2) What is the relationship between these mechanisms and other
      psychological phenomena? Using a qualitative methodology, six cognitive
      mechanisms are identified. Their use appears to be associated with both
      beneficial and detrimental subjective reactions. Findings from this study suggest
      that cognitive mechanisms are an important focus of inquiry because they may
      mediate the relationship between social exchanges and well-being.

PMID- 1399073
TI  - A five-year study of Hydron root canal fillings.
AB  - A prospective clinical and radiographic study was conducted in order to compare
      Hydron and laterally condensed gutta-percha/AH-26 root canal fillings.
      Paralleling technique periapical radiographs were taken preoperatively,
      postoperatively and at recall appointments at post-treatment intervals of 6
      months, 1 year, 2 years, 3 years and 5 years. Clinical examination at the recall
      appointments revealed no adverse signs or symptoms amongst all the patients who
      attended (mean attendance 44.5% at each interval). Radiographs were scored
      according to the periapical status of the treated root, and comparable bone
      healing rates were observed between the two root-filling materials. Among the
      patients attending recall appointments, there were no radiographic signs of
      failure of any of the 39 gutta-percha/AH-26 root canal fillings. However, three
      of the 35 canals filled with Hydron were classified as failures, and four
      required further assessment after the 5-year recall appointment. This study
      indicated that Hydron and gutta-percha/AH-26 root canal fillings were well
      accepted but, on the basis of radiographic assessment, success with gutta
      percha/AH-26 was more predictable.

PMID- 1399075
TI  - Employment, social networks, and health in the retirement years.
AB  - The impact of employment on the health of retirees is examined, with particular
      attention to the hypothesis that social roles affect health through their impact
      on social networks. Data are based on comprehensive assessment questionnaires
      completed by 175 participants of a corporate sponsored geriatric clinic. Results
      indicate that employment in the retirement years is related to larger social
      networks and indirectly, through this relationship, to better perceived health.
      Of the three social network factors identified through factor analysis: family,
      friends, and confidant relationships, employment was significantly related only
      to the friendship component. A summary analytic model is presented and
      implication for interventions are discussed.

PMID- 1399076
TI  - Quality in grandparent/grandchild relationships.
AB  - Five elements identified from the literature as expressive of quality in
      grandparent/grandchild relationships were used in this study. Three hundred
      ninety-one young adults at a midwest university responded to questions concerning
      the quality of their relationships with their "most close" grandparent. Responses
      of the students validated the following five elements of quality as being
      associated with successful grandparent/grandchild relationships: 1) a fairly high
      degree of closeness, 2) a strong sense of being known by the grandparent, 3) a
      strong sense of the young adult's knowing the grandparent, 4) a sense of the
      grandparent being a fairly strong influence in the life of the grandchild, 5) a
      sense of an authentic or independent grandparent/grandchild relationship not
      dominated by, but supported by, the middle generation. Analysis of variance
      identified the impact of seven independent variables on the quality of
      grandparent/grandchild relationships.

PMID- 1399077
TI  - The impact of stressful life events and social support on drinking among older
      adults: a general population survey.
AB  - This article is an analysis of stressful life events, the buffering hypothesis,
      and alcohol use in a national sample of 1,418 respondents 60 years of age and
      over. The results indicate that older adults who experience stressful losses are
      significantly more likely to drink excessively than those who have not
      experienced such losses or who have experienced them to a lesser extent.
      Increased drinking among older adults may therefore be a reaction to life
      circumstances in which alcohol represents an attempt to cope with traumatic loss,
      personal as well as within the kinship network. Supportive resources of spouse,
      family, friends, and church appear to have a stress-buffering effects that
      reduces the excessive-drinking response to life crisis. Data suggest, however,
      that older persons are vulnerable to the magnitude of losses experienced as they
      grow older and lose more of their family, friends, and peers. These stressors
      appear to seriously impact their drinking behavior and are not effectively
      buffered. Respondents report that drinking may increase during periods of
      prolonged exposure to emotionally depleting life change and loss, when supportive
      needs may exceed the capacities of personal and social support resources.

PMID- 1399078
TI  - African-American, Anglo-American, and Anglo-Canadian grade 4 children's concepts
      of old people and of extended family.
AB  - A cross-national study of 104 fourth grade children's concepts of old people and
      extended family was conducted in Canada and the United States, using the
      Children's Attitudes Toward the Elderly Scale (CATE), and a modified version of
      the Gilby and Pederson (1982) Family Concept Interview. Both Anglo-American and
      African-American children were included in the U.S. sample. Results indicated
      that Anglo-American and Anglo-Canadian children were significantly more similar
      in their attitudes toward the elderly and their concepts of family than African
      American and Anglo-American children. In comparison with the other two cultural
      groups, Anglo-American children were significantly more likely to include
      extended family members in their concept of who is family; Anglo-Canadian
      children had a significantly higher level of age discrimination ability; and
      African-American children showed a trend toward more positive attitudes toward
      older people. Overall findings of negative attitudes toward old people were
      consistent with earlier studies. The implications of children's ageist attitudes
      for increasingly aging Western societies are noted, particularly given
      impoverished children's potential need for extrafamilial social supports.

PMID- 1399079
TI  - Service utilization by well-organized frail elderly individuals.
AB  - In spite of extensive legislation intended to provide social services for elderly
      individuals, there is a lingering question about how much elderly persons
      actually use these services. This article reports findings from a study involving
      an innovative program called STAES (System to Assure Elderly Services), located
      in downtown St. Louis, Missouri and in particular finds that frail elderly
      individuals in the STAES program are using services in greater numbers than the
      review of the literature seems to suggest. In-home services such as homemaker
      services and visiting nurses' services are indeed used by elderly individuals who
      are in greater need than others. Through discussing the objective and operation
      of this program, the article explains why elderly individuals participating in
      the STAES program are effective users of publicly provided social services.

PMID- 1399080
TI  - Development of an interview-based geriatric depression rating scale.
AB  - The geriatric depression rating scale (GDRS) is a new interview-based depression
      rating scale designed for use with adults 60 years of age or older. The scale was
      developed to fill a need for an instrument that would be sensitive to the
      problems encountered in assessing depression among older adults. The GDRS was
      designed by using items from the self-report Geriatric Depression Scale (GDS) as
      topic areas in a structured clinical interview similar to that of the Hamilton
      Rating Scale for Depression (HRSD). The 35-item rating scale was administered to
      68 older individuals with a range of affective disturbance. The scale was found
      to have internal consistency and split-half reliability comparable to the HRSD
      and GDS. Concurrent validity, construct validity, external criterion validity,
      sensitivity, and specificity were all found to be acceptable.

PMID- 1399081
TI  - Socio-cognitive skills as a determinant of life satisfaction in aged persons.
AB  - The purpose of this study was to explore the viability of a revised model of
      elderly life satisfaction, specifically evaluating the contribution of socio
      cognitive skills. The role of such skills in relation to life satisfaction among
      aged persons has not been explored in research to date. Pilot data gathered from
      60 community-living aged individuals indicated that numerous variables (e.g.,
      subjective/objective health, education, financial satisfaction, role
      participation, subjective integration) significantly correlated with life
      satisfaction. However, the combined effects of two variables, persons' feelings
      of loneliness and isolation from their families and a measure of socio-cognitive
      skill, accounted for 49 percent of the variability in elderly life satisfaction.
      The effects of each on life satisfaction were unique however. Implications of
      these data and possible interventions for increasing elderly persons' life
      satisfaction are discussed.

PMID- 1399082
TI  - A comparison of office and adult day care center older volunteers: social
      psychological and demographic differences.
AB  - Numerous researchers have compared older adults who volunteer with those who do
      not volunteer on several demographic variables. In contrast, in the present study
      we compared older adults (minimum age = 55 years old) who volunteered to work for
      a community organization at an office or in a day care center on social
      psychological and demographic predictors. It was hypothesized that day care
      center volunteers would have higher scores than office volunteers on sympathy,
      role taking, and self-based salience of volunteer role (i.e., personal identity).
      In addition, office volunteers were expected to have higher scores than day care
      center volunteers on other-based salience of volunteer role (i.e., social
      identity). Discriminant function analysis indicated that day care center
      volunteers were higher than office volunteers on sympathy whereas office
      volunteers were higher than day care center volunteers on educational attainment,
      involvement in clubs and organizations, and role taking.

PMID- 1399083
TI  - Monitoring of spermatogenesis in man--measurement of Sertoli cell- or germ cell
      secreted proteins in semen or blood.

PMID- 1399084
TI  - Enhanced detection of reactive oxygen species produced by human spermatozoa with
      7-dimethyl amino-naphthalin-1, 2-dicarbonic acid hydrazide.
AB  - A new chemiluminescence technique has been assessed for the detection of reactive
      oxygen species generated by purified populations of human sperm. This revised
      protocol involves the use of horse-radish peroxidase (HRP) in combination with a
      luminol analogue, 7-dimethyl amino-naphthalin-1,2-dicarbonic acid hydrazide
      (DNDH), that exhibits two-three times the quantal efficiency of luminol itself.
      The chemiluminescent signal generated with these reagents was significantly (P
      less than 0.001) greater than that obtained with the conventional luminol-based
      methodology for both the steady-state situation and following stimulation of the
      sperm with PMA and A23187. Dose-response analyses indicated that the DNDH/HRP
      chemiluminescence system could give linear standard curves with hydrogen peroxide
      concentrations into the nmol l-1 range. In contrast, the exponential rise in
      chemiluminescence recorded with luminol was not observed until hydrogen peroxide
      concentrations exceeded 10 mumol l-1. It is concluded that the enhanced
      sensitivity of the DNDH/HRP system to low levels of hydrogen peroxide should
      facilitate the application of chemiluminescent techniques to the diagnosis of
      oxidative stress in cases of male infertility.

PMID- 1399085
TI  - Effect of isotypes of antisperm antibodies on semen quality.
AB  - A direct immunobead test (IBT) was performed on 233 men who attended an
      immunological centre. Thirty-four (14.6%) of these men were found to be positive
      (greater than 20% binding) for antisperm antibodies (ASA). IgA, IgG and IgM were
      the most common sperm-associated immunoglobulins. In 50% of men with ASA
      asthenozoospermia, teratozoospermia, leukocytospermia or hypofunction of the
      seminal vesicles was observed. Semen parameters were altered most frequently when
      IgM was present in association with IgA and/or IgG. This suggests that there is
      an active inflammatory process in the reproductive tract, as evidenced by
      leukocytospermia, and this could be responsible for the abnormal semen
      parameters. ASA generation could be a consequence of this process rather than
      being the cause of the abnormal semen quality. If ASA do affect fertility, this
      could take place in the female reproductive tract.

PMID- 1399086
TI  - Effect of zinc on human sperm motility and the acrosome reaction.
AB  - This study has assessed the effect of zinc on human sperm motility and the
      acrosome reaction in vitro. Progressively motile human sperm were selected by
      swim-up and by glass bead columns and then incubated in a medium in which
      capacitation happened in an asynchronous way. Different doses of zinc (1, 10, 100
      and 1000 microM) were added for periods of 2, 4 or 6 h. Other samples were
      incubated with zinc (1000 microM), and after 1 h incubation, the zinc was
      removed. Aliquots of each culture were used to evaluate progressive motility and
      the acrosome reaction using a triple-stain technique. Sperm motility was reduced
      when the amount of zinc added was greater than or equal to 100 microM, and these
      doses also caused a significant reduction in the % of sperm undergoing the
      acrosome reaction. After removal of zinc and further incubation in zinc-free
      medium for 1 h, an increase in the percentage of motile and acrosome-reacted
      sperm was observed. However, the increase in acrosome reaction did not reach the
      values observed in controls. Results suggest that extracellular zinc acts as an
      inhibitor of human sperm motility and the acrosome reaction (and/or capacitation
      and the acrosome reaction). This inhibitory effect is reversible and occurs in a
      dose-dependent fashion. The probable mechanisms involved are discussed.

PMID- 1399087
TI  - Acidification of testicular and epididymal fluids in the rat after surgically
      induced varicocele.
AB  - Experimental left varicocele (ELV) in adult rats produces a bilateral increase in
      testicular blood-flow and temperature which may alter the intraluminal
      environment in which sperm mature. The purpose of the present study was to
      evaluate the effect of ELV on the in-situ pH, PCO2 and bicarbonate concentration
      ([HCO3-]) in seminiferous tubules (ST), initial segment (IS), proximal caput
      (PCP), middle caput (MCP), middle corpus (MCR), and proximal cauda epididymidis
      (PCD) of the rat employing pH and PCO2 microelectrodes. Adult male rats with ELV
      or sham-surgeries (control) were studied after 30 days. Relative to controls, ELV
      significantly reduced the in-situ PCO2 in the testicular artery, ST, IS, PCP,
      MCP, MCR and PCD. In spite of this reduction, all values remained significantly
      higher than the systemic arterial blood PCO2. Values for in-situ pH in ST, IS,
      PCP, MCP, MCR, and PCD of control rats were significantly more acidic than
      systemic arterial blood. Furthermore, ELV decreased the pH in ST, IS, PCP, and
      MCP when compared to control values. The calculated [HCO3-] in ST from control
      animals was less than half that in systemic arterial blood and was reduced
      further in IS, PCP, and MCP. Varicocele did not change the [HCO3-] in systemic
      arterial blood but reduced markedly the values in ST, IS, PCP, and MCP. These
      alterations in the in-situ pH, PCO2, and [HCO3-] in structures of the rat testis
      and epididymis may play a role in the anti-spermatic effect of ELV.

PMID- 1399088
TI  - Effects of induced peripheral anosmia on gonadal maturation in prepubertal male
      rabbits.
AB  - The effect of induced peripheral anosmia on gonadal development and maturation
      was investigated in sexually immature male rabbits. Furthermore, the effect of
      agents promoting gonadal maturation (LHRH, hMG or methyl testosterone) on
      testicular development was examined in anosmic rabbits. Peripheral anosmia was
      induced by spraying the olfactory mucosa with 5% ZnSO4 solution; its effects were
      evaluated after a 45-day period, corresponding to the duration of
      spermatogenesis. Evaluation was based on measurement of body-weight, testicular
      size, testicular biopsy score count (TBSC) and a standard LHRH test (0 and 30
      min) involving measurement of the blood levels of FSH, LH and testosterone before
      and at the end of the test. Markedly lower final and incremental values were
      noted in anosmic, compared to intact, animals for body-weight (P less than
      0.001), TBSC (P less than 0.001), FSH (P less than 0.01) and LH (P less than
      0.05). On the other hand, treatment of the anosmic rabbits with 0.9% saline,
      resulted in lower FSH, TBSC and testicular size increments than in rabbits
      treated with LHRH, hMG or testosterone, while testosterone levels and body-weight
      increments were similar in all groups. These findings indicate that induced
      peripheral anosmia is probably responsible for the inadequate gonadal maturation
      in prepubertal anosmic male rabbits. This relationship was confirmed by the
      observed stimulatory effect of administration of agents activating pituitary
      gonadotrophin secretion or gonadal function in anosmic animals.

PMID- 1399089
TI  - Possible involvement of the accessory sex glands in the regulation of pituitary
      hormones.
AB  - A time-course alteration in the blood levels of gonadotrophin was evaluated in
      male rats aged 49 days after: (a) removal of the seminal vesicles, (b) bilateral
      orchidectomy, or (c) bilateral orchidectomy together with removal of the seminal
      vesicles. Age-matched sham-operated animals served as controls. Removal of the
      seminal vesicles resulted in elevation in the blood levels of LH, FSH and
      prolactin compared to controls. As expected, bilateral orchidectomy also resulted
      in the elevation of serum gonadotrophins. In the absence of both the seminal
      vesicles and the testes, LH and FSH levels were increased further compared to
      orchidectomy alone. Thus the present study suggests the presence of a feedback
      mechanism between the seminal vesicles and pituitary which is more pronounced in
      the absence of the testes.

PMID- 1399091
TI  - Model-based decision support system for individual prescription of the dialysate
      bicarbonate concentration in hemodialysis.
AB  - A decision support system has been developed that determines the optimal
      dialysate bicarbonate concentration in hemodialysis therapy for each patient
      individually. The knowledge about the behavior of the acid-base state during
      treatment has been provided by a mathematical model for the description of
      dynamic exchange processes during hemodialysis. This model simulates the sodium
      and water distribution, the acid-base state as well as the ventilation. The
      decision support system uses the model for the prediction of the end-dialysis
      acid-base state and calculates by means of linear optimization the dialysate
      bicarbonate concentration which is necessary to reach a specified end-dialysis
      state. If the aspired acid-base state can not be reached, the system varies the
      dialysate sodium concentration and the treatment time. The whole program can be
      used on a PC and is easy to use. One decision making process lasts between 10
      seconds and 5 minutes depending on the computer.

PMID- 1399090
TI  - Isolation and culture of testicular macrophages from a seasonally breeding
      species, Phodopus sungorus. Evidence for functional differences between
      macrophages from active and regressed testes.
AB  - We have developed an isolation and cultivation protocol for testicular
      macrophages from the seasonally breeding Siberian hamster, Phodopus sungorus
      which allows serum-free culture. Macrophages were isolated from the active testes
      of adult Phodopus kept in long photoperiod (LD, 18hL:6hD), and from the inactive
      testes of animals with gonadal regression induced by exposure to a short
      photoperiod (SD, 6hL;18hD; for 10 weeks). The isolated cells were identified as
      macrophages by (a) electron microscopy, (b) non-specific phagocytosis, and (c)
      the presence of Fc-receptors. Treatment of the cultures with oFSH (at 0.5 and 1
      micrograms ml-1 for 1 and 4 days) significantly stimulated lactate secretion by
      testicular macrophages from LD hamsters, as expected from studies in the rat. In
      marked contrast, oFSH did not affect lactate secretion by testicular macrophages
      from SD hamsters, or by peritoneal macrophages. To test possible macrophage
      Leydig cell interactions, the influence of testicular macrophage-conditioned
      medium (TM-CM) from FSH-responsive LD macrophage cultures was assessed and
      compared with the effect of peritoneal macrophage-conditioned medium (PM-CM) on
      testosterone production by testicular parenchyma from LD hamsters. Unexpectedly,
      and in contrast to previous reports in rats, testosterone production by testes
      was inhibited significantly by TM-CM from cultures pretreated with either 0.1 or
      0.5 micrograms FSH ml-1. FSH alone stimulated testosterone production (due either
      to LH contamination or to possible paracrine effects). PM-CM from cultures
      pretreated with FSH did have an inhibitory effect. It is concluded that: (i)
      There is indirect evidence for the presence of functional FSH receptors on
      macrophages from the active testes of Phodopus. (ii) Testicular macrophages from
      inactive testes of Phodopus are not responsive to FSH, implicating impaired
      macrophage function in the regressed testes of Phodopus exposed to SD. (iii)
      Testicular macrophages produce a factor which can inhibit testosterone production
      by incubated testicular tissue.

PMID- 1399092
TI  - Biocompatibility of high-flux membranes.
AB  - Standard dialysis with cuprophane membranes is known to stimulate the immune
      system. As a result of activation of macrophages various interleukins and tumor
      necrosis factor (TNF) are secreted, presenting further evidence of the poor
      biocompatibility of cuprophane. We investigated the immunogenic properties of
      three modern high-flux membranes. Seven patients were studied during
      hemodiafiltration sessions using either a polysulfone (F60, Fresenius), a
      polymethylmetacrylate (BK 2.1, Toray) or a cellulose triacetate (FB-210 U, Nipro)
      dialyzer in a hemodiafiltration procedure. Serial measurements were made during
      each treatment of interleukin-1 beta (II-1 beta), TNF, soluble IL-2 receptor (sII
      2r), soluble CD4 (sCD4), soluble CD8 (sCD8), interferon gamma (IFNg) and
      neopterin. In contrast to the known increase of IL-1 beta, IL-2r and TNF with
      cuprophane membranes, none of the modern high-flux dialyzers stimulated the
      production of these factors. Significant decreases of neopterin and sCD4 were
      observed. IFNg and sCD8 did not change significantly. Our results suggest that
      the modern high-flux dialyzers are non-immunogenic, and thus provide further
      evidence of the superior biocompatibility of synthetic or semisynthetic membranes
      over the conventional cuprophane.

PMID- 1399093
TI  - Disinfection of regenerated dialyzers with ozone.
AB  - Regenerated, ozone-disinfected dialyzers were use for a total of 190 hemodialyses
      in 35 patients without the occurrence of any complication or pyrogen reactions;
      the efficiency of hemodialysis was identical with that of new or formalin
      disinfected dialyzers. The priming fluid contained in both compartments of ozone
      disinfected dialyzers proved to be sterile. The ozone did not damage the dialyzer
      membrane or the supporting structure of dialyzer. Ozone can effectively
      substitute formalin and other chemical sterilants as a disinfectant of
      regenerated capillary dialyzers. The process can also be automated.

PMID- 1399094
TI  - Differences between KT/V measured during dialysis and KT/V predicted from
      manufacturer clearance data.
AB  - We retrospectively analyzed data from 3,863 dialysis treatments in 329 end-stage
      renal disease patients over a period of 33 months to evaluate the accuracy of in
      vitro KT/V estimated by manufacturer's urea clearance data in relation to in vivo
      measured KT/V. In 1,087 urea clearances measured, mean actual clearance was 87%
      of predicted. At all blood flows, actual clearances were significantly lower than
      predicted (8-16% lower than predicted). In 2,807 KT/V measurements, predicted
      KT/V was 1.238 +/- 0.005 whereas the mean of actual measured KT/V was 16% lower
      or 1.024 +/- 0.005 (P less than 0.0001). At different blood flows and with
      different dialyzers, predicted KT/V overestimated actual values. With increasing
      numbers of reuse, actual/predicted clearance ratios and actual/predicted KT/V
      ratios progressively dropped. Prescribing dialysis treatments using
      manufacturer's in vitro generated clearance data can lead to marked underdialysis
      of patients.

PMID- 1399095
TI  - Blood flow rate and access recirculation in hemodialysis.
AB  - We studied the effect of extracorporeal blood flow rate (BFR) on access
      recirculation (recirc) in 19 hemodialysis patients. BUN was determined in
      simultaneous peripheral (P), arterial (A), and venous (V) blood obtained at BFRs
      of 200, 400, and 600 ml/min. Percent recirc was calculated for each BFR using the
      formula (P-A)/(P-V) x 100. Venous drip-chamber (VP) and pre-blood-pump (AP)
      pressures were measured at each BFR. Fistulograms were performed in 10 patients,
      and stenoses were identified in 5, all at the proximal (arterial) end of the
      access. Recirc increased with increasing BFR from 200 to 400 ml/min but increased
      little from 400 to 600 ml/min. At all BFRs recirc in the stenotic patients was
      higher than that of non-stenotic or unstudied patients. Urea clearance, corrected
      for recirc, rose with blood flow both in stenotic and non-stenotic patients.
      There were no differences in AP or in VP between stenotic and non-stenotic
      patients. At BFR greater than or equal to 400 ml/min, a recirc threshold of 15%
      identified stenoses with sensitivity 100% and specificity 71%. We conclude (1)
      recirc increases with increasing BFR but not enough to outweight the concomitant
      increase in urea clearance; (2) significant access stenosis and recirc may be
      present even with low VP; (3) recirc was associated with arterial side stenoses;
      (4) at BFR greater than or equal to 400 ml/min, access stenosis is associated
      with recirc greater than 15%.

PMID- 1399096
TI  - Prolonged extracorporeal circulation for acute myocarditis.
AB  - Total circulatory support for acute reversible myocardial failure is rarely used
      in clinical situations outside the postoperative period following cardiac
      surgery. We treated an 8-year-old girl who suffered acute viral myocarditis and
      sustained cardiac arrest requiring cardiopulmonary bypass for resuscitation. This
      was accomplished with the use of the portable cardiopulmonary support system
      (CPS), which consists of a centrifugal pump and a membrane oxygenator. This
      patient was placed on CPS in Hawaii and transported after 3 days to San Diego
      (4200 km) for further mechanical support and possible heart transplantation.
      Adequate cardiac function returned and CPS was stopped after 6 days. She is alive
      and well, attending school two and a half years after the event. Prolonged use of
      CPS for acute myocardial failure outside the operating room, including long
      distance transportation, is effective and easily accomplished with currently and
      widely available equipment, and should be used in acute, reversible catastrophic
      heart disease.

PMID- 1399097
TI  - Electromechanical artificial heart with a new gear type and angled pump chambers.
AB  - The intrathoracic anatomical situation after explantation of the natural heart
      defines the maximum available space for the design of the housing as well as of
      the inlet- and outlet connectors of a fully implantable electromechanical
      artificial heart. Based on computer-assisted anatomical studies, a total
      artificial heart housing is designed which facilitates an oblique orientation of
      the pumping chambers for a better fluidmechanical and anatomical arrangement of
      the in- and outlet connectors. The pumping chamber geometry is based on
      modifications of an existing cardiac assist-system. Subsequently a mechanical
      gear which conforms to this anatomically adapted housing is developed.

PMID- 1399098
TI  - Dynamic cardiomyoplasty in a patient with end-stage cardiomyopathy.
AB  - Dynamic cardiomyoplasty is a relatively new surgical procedure by which a
      transformed fatigue-resistant skeletal muscle wrapped around the heart is
      stimulated to contract in synchrony with it, thereby augmenting the ventricular
      functions of a failing heart. We performed a cardiomyoplasty with latissimus
      dorsii (LD) in a patient who was refused the heart transplant programme because
      of pulmonary hypertension and psychosocial contraindications. The patient was 34
      years old, functional class grade IV of the New York Heart Association (NYHA),
      with a three-month history, due to ischemic cardiomyopathy with multiple vessels
      affected, 10% ejection fraction, arteriolar pulmonary resistance of 7.5 U Wood.
      Cardiomyoplasty was performed after training the LD muscle for four weeks. One
      week later the pacemaker was programmed in a DDD mode: amplitude 3.75 V, pulse
      duration 0.50 ms, AV delay 175 ms. The patient reached functional class grade I
      II (NYHA). Inotrope support was discontinued and great clinical improvement was
      noted. The ejection fraction rose from 10% to 30%. Echocardiographic left
      ventricular outflow tract velocity increased from 0.33 m/s to 0.60 m/s. These
      values were compared with radionuclide angiocardiography and echocardiography
      evaluations. The great clinical improvement and positive changes in left
      ventricular parameters suggest that cardiomyoplasty is useful in the treatment of
      some cases of dilated or ischemic cardiomyopathy as an alternative to heart
      transplantation. Long term follow-up is necessary to evaluate this procedure.

PMID- 1399099
TI  - Dynamic pumping performance of the Hemopump--a small intraventricular blood pump.
AB  - We studied the pumping characteristics of the Hemopump, a commercially available
      miniature intraventricular blood pump for temporary support of failing hearts.
      The Hemopump is an axial flow pump of which the characteristics can be described
      by turbomachine theory. Experiments with water and a mock circulation verified
      that the pumping characteristics of the Hemopump in terms of both pressure head
      and flow as a function of rotational speed, very well can be described by a first
      order differential equation. The influence of blood with its non-Newtonian
      character is being investigated.

PMID- 1399100
TI  - Is calcium carbonate a safe phosphate binder in children with chronic renal
      failure?

PMID- 1399101
TI  - Abstracts of the XIXth ESAO Congress. European Society for Artificial Organs.
      Rodos, Greece, 14-17 October 1992.

PMID- 1399102
TI  - Changes of intraocular pressure in patients with open-angle glaucoma in relation
      to the passage of atmospheric fronts and environmental contamination.
AB  - Effects of atmospheric frontal passages on intraocular pressure (IOP) in patients
      with open-angle glaucoma are statistically investigated to show the
      meteorotropism of this disease. Changes in IOP caused by frontal passages are
      evident; the response is not identical in all the patients near the day of the
      passage of a warm front, while on the third day following the passage of the
      front a well pronounced drop in IOP occurs. Anomalous increases of IOP over
      several months' duration occurred in the years 1986-7. This finding is explained
      in relation to the hypothesis of environmental contamination in Central Europe by
      radioactive cesium nuclides due to the Chernobyl accident.

PMID- 1399103
TI  - Effect of inspiratory resistance to prolonged exercise in a hot environment
      wearing protective clothing.
AB  - The effects of inspiratory resistance on prolonged work in a hot environment
      wearing a nuclear, bacteriological and chemical warfare (NBCW) mask and
      overgarment were assessed in 10 males. Subjects walked on a treadmill at 5 km/hr,
      2% gradient, until their core temperature reached 39 degrees C or for a duration
      of 90 min. Rectal temperature, heart rate, ventilation, oxygen consumption and
      rate of perceived breathing were measured. There were no differences between
      break-point time without the canister (62.2 +/- 21 min) and with the canister
      (58.9 +/- 17 min). Regression analysis indicated that the mean core temperature
      increased by 0.02 degrees C for every minute of work performed and heart rate by
      6 beats/min for every increase of 0.2 degrees C in core temperature. Reduction in
      heat transfer brought about by wearing the protective overgarment and mask with
      or without the canister will significantly increase core temperature and limit
      the performance of moderate work to approximately 1 h in a moderately fit
      individual.

PMID- 1399104
TI  - Correlation analysis between some blood properties and atmospheric environmental
      parameters.
AB  - S.W. Tromp made investigations of a weather effect on erythrocyte sedimentation
      rates (ESR) of human blood by routine checks of the blood of donor groups in
      Leiden from 1955 to 1985. A higher ESR was found for the summer season and lower
      ESR for winter and low values occurred soon after a strong cooling spell. In this
      report, we have continued his work using data for the years 1971-1985 from Leiden
      (The Netherlands). An influence of the weather on ESR was also found, but this
      seems to be more complicated than Tromp supposed. Some new aspects are described
      and elaborated, e.g. ESR already increases before warming is noticed at the
      ground layer. This is possibly caused by changes in the upper atmosphere, a
      suggestion that requires further studies. For periods of low ESR, there was a
      greater number of occlusion fronts passing the Netherlands. The long-term
      fluctuations of ESR that were found were correlated with sun spot relative
      numbers only in a few periods. The results of our study justify further research
      for a variety of other locations around the world.

PMID- 1399105
TI  - Influence of season and microclimate on fertility of dairy cows in a hot-arid
      environment.
AB  - Records were obtained over a 3 year period from six Holstein dairy farms of 300
      to 500 cows each in the Phoenix, Ariz. area. Dairies were selected on the basis
      of similar management practices, herd size, milk production and facilities (with
      the exception of cooling systems). Microclimatic modifications (two dairies each)
      were shade only (approximately 3.7 m2/cow), evaporative-cooled shades and low
      pressure water foggers under the shades. Data were categorized by season of
      calving (spring, Feb.-May; summer, June-Sept.; and fall, Oct.-Jan.). Traits
      evaluated were calving interval, days open and services/conception. Calving
      interval was shortest for cows calving in the spring (378 days), intermediate in
      fall (382 days) and longest in summer (396 days). Similar seasonal trends were
      observed for days open (103, 103 and 119 days, respectively) and
      services/conception (1.54, 1.81 and 1.93, respectively). All differences between
      spring and summer were significant (P less than 0.05). Calving interval and days
      open were less for evaporative-cooled groups (374 and 98 days, respectively),
      with no difference between shade only and foggers (391 and 392 days, 112 and 116
      days, respectively). Services/conception were similar for all groups (1.72 to
      1.79). A significant interaction between microclimate and season for
      services/conception could be interpreted as (i) smaller season differences for
      evaporative-cooled groups than for shade or foggers, or (ii) a change in the
      ranking of control and fogger groups during summer versus fall. Evaporative
      cooling was more effective than fogging for reducing the detrimental effects of
      seasonal high temperatures on fertility.

PMID- 1399106
TI  - The influence of thermal conditions on rectal temperature, respiration rate and
      pulse rate of lactating Holstein-Friesian cows in the humid tropics.
AB  - The effect of minimum, maximum and mean ambient air temperatures and the
      temperature-humidity index (THI) of the same and the previous day on morning
      (a.m.) and afternoon (p.m.) rectal temperatures (RT), respiration rates (RR) and
      pulse rates (PR) were studied in 17 Holstein-Friesian cows over the first 125
      days in the 3rd and 4th lactations. Physiological responses showed a diurnal
      pattern, being lower in the mornings than the afternoons: 38.6 vs 39.0 degrees C
      for RT, 52.2 vs 60.7 breaths/min for RR and 58.1 vs 64.1 beats/min for PR.
      Correlations between RT and RR (r = -0.043 to -0.046) and RT and PR (r = -0.178
      to -0.261) were low (P greater than 0.05). Correlations between RR and PR (r =
      0.353 to 0.365) were moderate (P less than 0.05). Weather variables, especially
      ambient temperature of the previous day, were more important and influenced
      physiological responses to a greater extent than other thermal factors the same
      day. Generally, physiological responses were influenced to a greater extent by
      ambient temperature than THI. Weather variables explained variations in RT (5.1
      59.6%), in RR (13.0-17.8%) and in PR (22.1-25.4%). Relationships between weather
      variables the previous day and physiological responses were contradictory, with
      minimum and maximum values showing a negative relationship in contrast with a
      positive relationship for mean values.

PMID- 1399107
TI  - Plasma hormonal and electrolyte alterations in cycling buffaloes (Bubalus
      bubalis) during hot summer months.
AB  - Plasma levels of progesterone, prolactin, luteinizing hormone, and electrolytes
      were monitored by radioimmunoassay in ten cycling buffaloes maintained at Punjab
      Agricultural University, Ludhiana during the hot summer months of June-July. The
      plasma progesterone concentration ranged from 0.28 +/- 0.04 to 3.09 +/- 0.03
      ng/ml at various stages of the oestrous cycle. Prolactin values ranged from 319
      +/- 23 to 371 +/- 25 ng/ml and LH levels from 0.95 +/- 0.05 to 1.35 +/- 0.08
      ng/ml. Concentrations differed significantly (P less than or equal to 0.05) at
      various stages of the cycle. Levels of electrolytes, viz. Ca++, Na+ and K+, were
      well within the normal range. The high levels of prolactin, progesterone and LH
      during the hot summer were assessed in relation to poor reproductive efficiency
      in buffaloes.

PMID- 1399109
TI  - Lipoprotein(a) and CA125 levels in the plasma of patients with benign and
      malignant ovarian disease.
AB  - Elevated plasma levels of apolipoprotein (a) have been reported earlier in cancer
      patients. In order to investigate the potential of apolipoprotein(a) as an
      ovarian tumour marker, plasma apolipoprotein(a) and CA125 levels were measured in
      healthy women and women with benign or malignant pelvic masses. Among women
      younger than 49 years, 80% of healthy controls and ovarian cancer patients had
      apolipoprotein(a) levels below 350 U/l. Among women aged 49 years or older, 46%
      of healthy controls but 73% of ovarian cancer patients and 77% of women with
      successfully treated ovarian cancer, had low apolipoprotein(a) levels. For both
      age groups, apolipoprotein(a) is not a suitable marker for ovarian cancer. No
      correlation was found between apolipoprotein(a), triglyceride or cholesterol in
      plasma. Healthy women younger than 49 years had significantly higher CA125 levels
      than women 49 years or older (20 +/- 14 U/ml vs. 13 +/- 12 U/ml, p less than
      0.005). Levels of CA125 above 35 U/ml were found in 12% of the younger and 4% of
      the older healthy women, 73% of the younger and 61% of the older patients with
      untreated or residual tumours, and in 33% of the younger and 31% of older
      patients with no evidence of disease, as well as in 58% of women of both age
      groups with benign pelvic masses. The sensitivity and specificity of CA125 levels
      for the detection of cancer were 73% and 74% respectively for women younger than
      49 years, and 62% and 78% respectively for women 49 years or older.

PMID- 1399108
TI  - Interaction between heat acclimation and exogenous insulin in brown adipose
      tissue of rats.
AB  - Seventy-one male Wistar strain rats (7 weeks old) were kept at 5, 25, or 34
      degrees C, respectively, for 2 weeks with or without insulin administration.
      Insulin (Novo Lente MC) was given subcutaneously in a dose of 3.62 nmol/125
      microliters saline per 100 g body weight. An apparent effect of insulin treatment
      was noted only in heat-exposed rats, resulting in a remarkable gain in
      interscapular brown adipose tissue (BAT) mass of heat-acclimated, insulin-treated
      rats in terms of weight or weight per unit body weight. The BAT from heat
      acclimated, insulin-treated rats had significantly higher levels of protein, DNA,
      RNA, and triglyceride than BAT from heat-acclimated, saline-treated rats.
      Therefore, it seems likely that the growth of BAT in heat-acclimated, insulin
      treated rats was mostly due to the anabolic effects of insulin. The uncoupling
      protein mRNA was, however, present in BAT of heat-acclimated, insulin-treated
      rats at rather a depressed level, explaining a corresponding decrease in cold
      tolerance. On the other hand, the expression of insulin receptor mRNA was
      attenuated in BAT of rats from all the insulin-treated groups, possibly due to
      the down-regulation of insulin. Thus, there appeared to be some linkage among
      BAT, heat acclimation, and insulin.

PMID- 1399110
TI  - Ornithine decarboxylase assay in human colorectal mucosa. Methodologic issues of
      importance to quality control.
AB  - Ornithine decarboxylase may be a useful biomarker for risk of neoplasia in
      colorectal tissues. Investigators have reported enzyme activities varying by as
      much as 10- to 20-fold using variations of the usual 14CO2 release assay. We have
      examined the effect of different methodologic factors on calculated ornithine
      decarboxylase activity. Major effects on the assay result (greater than 20%
      change) were produced by: (1) use of Tris vs. phosphate buffer, the former
      yielding 1.5- to 4-fold greater activity; (2) protein content of the reaction
      mixture with significant error if less than 50 micrograms; (3) use of alpha
      difluoro-methylornithine-inhibited blank versus buffer-only blank. Other changes
      in assay conditions, including addition of sucrose, detergent, protease
      inhibitors, specific activity of 14C-ornithine, the nature of the trapping agent
      used, and incorporation of a sonication step, did not have a significant effect
      on ODC quantification (less than or equal to 20%). Thus, seemingly minor
      variations in assay conditions can greatly affect the results, which may provide
      a partial explanation for the variability of ODC activities reported in the
      literature. Strict quality control measures are mandatory in the interpretation
      of clinical observations utilizing this marker as an endpoint.

PMID- 1399112
TI  - Immunogenic tumor variants induced by drug treatment of the L5178Y lymphoma:
      search for serologically defined antigens at the clonal level.
AB  - Highly immunogenic tumor variants are generated by in vitro or in vivo treatment
      of the murine L5178Y lymphoma line with triazene derivatives. Most of these
      variants express new transplantation- and antibody-defined antigens that previous
      studies have shown to be closely related. One such 80-kDa protein on the surface
      of clone-D cells was found to be related to xenotropic MuLV gp70 molecules. To
      investigate the possible relevance of clone-D data to general properties of
      immunogenic variants in this tumor model system, polyclonal syngeneic antisera
      raised to a panel of immunogenic clones (including clone D) of the drug-treated
      L5178Y lymphoma line were employed in the immunoprecipitation of cell-surface and
      intrinsically labeled variant cells. In all clones, 1- and 2-dimensional
      electrophoretic analysis of the immunoprecipitates detected an antigen of
      approximately 80 kDa, and 35S-labeled 80-kDa molecules could be cross
      precipitated from all clones by the panel of clone-specific antisera. In
      addition, 45- and 30-kDa components were also found in metabolically labeled
      variant cells. While the surface 80-kDa component was reactive with anti
      xenotropic gp70 antibodies, the 30-kDa molecule was removed by anti-gag p30
      antibody in sequential immunoprecipitation experiments. These data suggest that
      expression of aberrant, retrovirus-related proteins is a common finding in
      immunogenic cells of the drug-treated L5178Y lymphoma line.

PMID- 1399111
TI  - Secretion of gelatinases and tissue inhibitors of metalloproteinases by human
      lung cancer cell lines and revertant cell lines: not an invariant correlation
      with metastasis.
AB  - Numerous studies have reported a correlation between production of 72-kDa (MMP-2)
      and 92-kDa (MMP-9) type-IV collagenases/gelatinases and the metastatic potential
      of cancer cells. An abrogating effect of tissue inhibitors of metalloproteinases
      (TIMP-1 and TIMP-2) on metastases has also been noted. In this report we have
      used sensitive enzyme-linked immunoassays to measure MMP-2, MMP-9, TIMP-1 and
      TIMP-2 levels in eight human lung-cancer cell lines which were characterized for
      biological behavior in nude mice. We demonstrated that the Calu-6 and A549 cell
      lines with the highest metastatic, invasive and tumorigenic potential secreted
      the highest levels of MMP-2. MMP-9 and TIMP-1 secretions were comparatively low
      in all cell lines. TIMP-2 secretion, which exceeded MMP-2 secretion for all cell
      lines, did not correlate with metastatic potential. To further explore these
      correlations, the metastatic Calu-6 cell line was transfected with a K-rev-1 cDNA
      expression construct. The K-rev revertant cell lines demonstrated a more
      differentiated phenotype and were less tumorigenic, invasive and metastatic in
      nude mice. Nonetheless, the Calu-6 revertant cell lines secreted higher levels of
      MMP-2 than the parent cell line. In conclusion, invasion and metastasis by lung
      cancer cells requires not only enhanced MMP production, but also other less well
      understood tumorigenic characteristics. The multiplicity of factors required by
      cancer cells for dissemination helps to explain the minute fraction of cancer
      cells from a primary tumor that ever develop into a metastasis.

PMID- 1399113
TI  - A basement-membrane permeability assay which correlates with the metastatic
      potential of tumour cells.
AB  - We describe an in vitro assay for measuring the ability of tumour cells to
      permeabilize basement membranes, using transwell chambers coated with the
      reconstituted basement membrane, matrigel. Unlike previous matrigel-based
      procedures which quantified passage of tumour cells across a matrigel barrier,
      the new assay measures the ability of tumour cells to degrade the basement
      membrane and increase the diffusion rate of fluorescent (FL) dextran through the
      barrier. The procedure has the major advantage that permeability can be rapidly
      and accurately quantified, either by fluorometry or by the use of radiolabelled
      dextran, thus avoiding tedious and subjective scoring methods. Optimal conditions
      for the assay are described. In addition, it is demonstrated that the assay can
      clearly discriminate between metastatic and non-metastatic tumour cell lines,
      metastatic tumours permeabilizing the basement membrane and non-metastatic
      counterparts failing to do so. A range of enzyme inhibitors suggested that the
      increase in basement-membrane permeability caused by the metastatic mammary
      adenocarcinoma 13762 MAT is probably dependent upon the synergistic action of
      several degradative enzymes, namely proteases, type-IV collagenase, and
      heparanase. Furthermore, the ability to permeabilize the basement membrane was
      dependent upon intact tumour cells; tumour cell extracts, lysates and
      supernatants were inactive.

PMID- 1399114
TI  - Glucose depletion enhances the anti-tumor effect of TNF.
AB  - Treatment of human carcinoma xenotransplants in athymic mice with recombinant
      human tumor necrosis factor (rh TNF) causes necrosis mainly in the central parts
      of the tumors, while peripheral sections remain mitotically active. As tumors are
      known to be supplied with adequate glucose exclusively in their periphery, the
      influence of the lack of glucose on the cytotoxic activity of rh TNF was studied.
      The absence of glucose enhanced the killing of tumor cell lines by rh TNF in
      tissue culture. Meth-A, a cell line known to be resistant to TNF in vitro but
      highly sensitive to it in vivo, was readily killed in tissue-culture medium
      lacking glucose. All non-transformed cell lines tested were found to be resistant
      to rh TNF, regardless of the presence or absence of glucose. In tumor-bearing
      mice a reduction of the blood glucose content augmented by insulin led to
      increased anti-tumor efficiency of rh TNF. The enhanced anti-tumor activity was
      reflected both in histological sections of the tumor xenotransplants, by
      extensive central necroses, and by reduction of the tumor volumes.

PMID- 1399115
TI  - Induction of protein kinase C down-regulation by the phorbol ester TPA in a
      calpain/protein kinase C complex.
AB  - Using a calpain/protein kinase C (PKC) complex, we were able to reproduce, in
      vitro, the induction of PKC down-regulation by the phorbol ester 12-O
      tetradecanoyl-phorbol-13-acetate (TPA) which had been previously observed in
      cells. We show that TPA initiates this phenomenon by promoting a calpain
      dependent conversion of PKC to the Ca2+ phospholipid-independent protein kinase M
      (PKM), at physiological calcium concentrations. This effect of TPA was dependent
      upon the presence of phosphatidylserine and was observed only when PKC was the
      substrate for the protease, inactivation of calpain by autolysis not being
      modified by the presence of TPA. Moreover, PKM generated from the calpain-PKC
      complex was resistant to calpain, even after addition of TPA. These results
      suggest that TPA induces a conformational change in PKC, increasing the affinity
      of the kinase for calpain and consequently permitting its proteolysis for the
      basal level of calcium in cells.

PMID- 1399117
TI  - Production of stable phenotypes from 9L rat brain tumor multicellular spheroids
      treated with 1,3-bis(2-chloroethyl)-1-nitrosourea.
AB  - During chemotherapy and regrowth of brain tumors, tumor-cell heterogeneity, and
      possibly tumor progression, may change as a result of both the selective forces
      and mutagenic effects of treatment. We have isolated and characterized drug
      response variants of multicellular rat 9L brain-tumor spheroids exposed to 1,3
      bis(2-chloroethyl)-1-nitrosourea (BCNU). Ten colonies were isolated from
      spheroids disaggregated immediately after treatment, and 10 colonies were
      isolated from treated spheroids disaggregated after 1 week in suspension culture.
      The sensitivity to BCNU was determined by assays of sister chromatid exchange and
      colony-forming efficiency in monolayer cultures of each subline after a 1-hr
      exposure to graded doses of BCNU. Three classes of response were found: BCNU
      sensitivity increased, decreased, or was comparable to that of uncloned, parent
      9L cells. Resistant phenotypes were predominant (8/10) in sublines from spheroids
      disaggregated immediately after treatment, whereas hypersensitive phenotypes
      (4/8) were isolated only from spheroids disaggregated after 1 week of regrowth.
      Since subpopulations isolated immediately after treatment do not have the same
      biological characteristics as those isolated after a period of regrowth, these
      data suggest that tumor-cell heterogeneity may be generated by distinct processes
      at various times during therapy. The predominance of hypersensitive sublines
      obtained by the regrowth protocol may have resulted from the recovery of cells
      that would have died if isolated but were instead able to repair the drug-induced
      damage when left in contact with neighboring, possibly resistant cells. Two
      resistant and two hypersensitive sublines were studied further.

PMID- 1399116
TI  - Insulin-like growth factor II in two human colon-carcinoma cell lines: gene
      structure and expression, and protein secretion.
AB  - Abnormal expression and structural modification of the IGF-II gene in correlation
      with high IGF-II production have recently been described in human colorectal
      tumors in comparison with normal adjacent tissues. Here, we have studied IGF-II
      in 2 human colon-carcinoma cell lines, HT29 and COLO 320DM. RFLP analyses
      revealed no apparent alteration at the IGF-II locus in these 2 cell lines. HT29
      cells weakly expressed IGF-II mRNA in comparison with the high over-expression
      previously observed in some colorectal tumors, and only the 4.8-kb mRNA species
      was present. In addition, the serum-free medium conditioned by HT29 cells
      contained high IGF-II levels (approx. 900 ng/10(8) cells), as measured in a
      specific IGF-II radioimmunoassay (RIA). After chromatography on Bio-Gel P-60, we
      observed that 64% of the total IGF-II secreted by HT29 cells were present as a
      high-molecular-weight form of about 17 kDa. In contrast, no detectable expression
      of the IGF-II gene was observed in COLO 320DM cells, and low IGF-II levels were
      secreted by these cells in the serum-free medium, with only 9% total IGF-II
      represented by the large species.

PMID- 1399118
TI  - Influence of the estrous cycle at gamma-ray exposure on radiation-induced mammary
      tumorigenesis in virgin rats.
AB  - Wistar rats received whole body irradiation with 260 cGy gamma-rays at 10 a.m. of
      individual phases of their estrous cycle and then had diethylstilbestrol pellets
      implanted for 1 year. When the radiation was given during di-estrus II, the
      highest incidence (73.3%) of mammary tumorigenesis was observed, and mean latency
      until the first tumor appearance was 8.5 +/- 0.7 months. Also, rats irradiated on
      estrus had significantly lower incidence (35.3%) of mammary tumors than those
      irradiated on pro-estrus and di-estrus II, but there was no significant
      difference in latency period. Iball's indices of total mammary tumors,
      fibroadenoma plus adenocarcinoma, were 14.3 +/- 0.9, 28.8 +/- 2.1, 23.3 +/- 0.8
      and 12.2 +/- 0.2 in rats irradiated during di-estrus I, di-estrus II, pro-estrus
      and estrus respectively. The percentage of adenocarcinomas was comparatively
      uniform (25.0 to 34.8%) throughout the various phases of the estrous cycles.
      Also, Iball's indices calculated from adenocarcinoma indicated no significant
      differences between all groups. From our results, the highest incidence of
      mammary tumors arose in rats after irradiation at di-estrus II with minimum level
      of prolactin in serum. We discuss different mechanisms of radiation-induced and
      chemical-carcinogen-induced tumorigenesis of mammary glands.

PMID- 1399119
TI  - Enhanced epidermal growth factor receptor synthesis in human squamous carcinoma
      cells exposed to low levels of oxygen.
AB  - Exposure of human A431 squamous carcinoma cells to levels of hypoxia found in
      some solid tumors causes 2-fold increases in epidermal growth-factor receptor
      (EGF-R) mRNA levels and rate of receptor protein synthesis compared with aerobic
      cells. Similar results are shown for receptor message from other squamous
      carcinoma cells, human keratinocytes, and human W138 fibroblasts. Less basal
      tyrosine phosphorylation of the receptor occurs in hypoxic compared with aerobic
      A431 cells. Scatchard analysis also shows that reoxygenated A431 cells display
      enhanced surface expression of the EGF-R compared with aerobic control cells.
      Possible mechanisms and implications for tumor therapy are discussed.

PMID- 1399120
TI  - Distribution and photosensitizing efficiency of porphyrins induced by application
      of exogenous 5-aminolevulinic acid in mice bearing mammary carcinoma.
AB  - By means of a chemical extraction procedure and confocal laser scanning
      microscopy, we investigated the kinetic patterns of uptake and biolocalization of
      5-aminolevulinic acid (ALA)-induced porphyrins in s.c. transplanted tumors,
      adjacent normal skin and muscle, and liver of mice bearing mammary carcinoma,
      after i.p. injection of 250 mg/kg ALA or topical application of ALA (20% in an
      oil-in-water emulsion). Furthermore, we evaluated the tumor responses after
      either i.p. injection or topical application of 5-ALA followed by laser
      irradiation (632 nm, 150 mW/cm2, 25 min) by measuring the treated tumor
      regression/regrowth time and by light and electron microscopy. Strong
      fluorescence of ALA-induced porphyrins was detected in the tumor, skin and liver
      tissues, while little fluorescence was seen in the adjacent muscle tissue.
      Moreover, the highest amounts of ALA-induced porphyrins in the tumor and skin
      tissues were found 1 hr after i.p. injection, whereas the amounts of the
      porphyrins in both tissues increased with increasing time after topical
      application of ALA. The fluorescence of the porphyrins was localized in several
      components of the skin tissue (epidermis, hair follicles and their associated
      sebaceous glands). Furthermore, the fluorescence was diffusely distributed in the
      s.c. transplanted tumor tissue. Little could be observed under a confocal laser
      scan microscope (CLSM) in the muscle tissue. The uptake and biolocalization data
      correlate well with the results of PCT efficiency of the same tumor model with
      ALA-induced porphyrins. Light and electron microscopy showed that the
      mitochondria of the tumor cells and of the endothelial cells and the basal lamina
      of vascular walls beneath the endothelium in the tumor tissue were initially
      extensively destroyed after PCT with ALA-induced porphyrins. Thereafter, diffuse
      degeneration followed by local and/or diffuse severe necrosis of the tumor cells
      was found. This may be due mainly to the initial damage to mitochondria in the
      cancerous and endothelial cells and also to the destruction of the vascular wall
      in the tumor tissue.

PMID- 1399121
TI  - Bile acids, non-phorbol-ester-type tumor promoters, stimulate the phosphorylation
      of protein kinase C substrates in human platelets and colon cell line HT29.
AB  - Protein kinase C (PKC) is the target for a number of tumor promoters. The
      mechanism underlying the promoting effects of bile acids in colorectal cancer is
      not understood. We report that sodium deoxycholate (DOC) triggered activation of
      PKC in physiological conditions. The biphasic effects of DOC upon PKC activation
      were Ca(2+)-stimulated and did not require phosphatidylserine (PtdSer) as
      phospholipid co-factor. The optimal rate of activation was obtained at 0.4 mM DOC
      and reached approximately half the maximal rate of activation obtained in the
      presence of PtdSer. Similarly to PtdSer, DOC supported diacylglycerol- as well as
      phorbol-ester-mediated PKC activation. The reciprocal effects of PtdSer and DOC
      upon PKC in either 0.5 mM CaCl2 or 0.5 mM EGTA suggest that DOC interacts with
      the phospholipid-binding domain to elicit PKC activation. DOC-supported enzyme
      activation exhibited substrate specificity different from that of PtdSer
      supported enzyme activation. All tested primary and secondary bile acids
      activated PKC to various extents, with DOC being the most potent. We suggest that
      amphipathic bile acids acting in a PtdSer-like manner provide the hydrophobic
      environment required for PKC activation. Treatment of 32P-labeled platelets and
      colonic cells HT29 Cl.19A with DOC enhanced the phosphorylation of endogenous
      substrates for PKC. Colonic cells responsive at 50 microM DOC, appeared to be 10
      fold more sensitive than platelets. We suggest that direct or indirect activation
      of PKC by bile acids may account for the promoting effects of these non-phorbol
      ester-type tumor promoters.

PMID- 1399122
TI  - Spontaneously transformed rat-liver epithelial-cell line producing autocrine and
      paracrine growth factors.
AB  - A spontaneously transformed rat-liver epithelial-cell line that could
      proliferative in unsupplemented, serum-free medium and be passaged with
      trypsinization has been established. At the time of writing, the line has
      undergone more than 100 passages in serum-free culture. This cell line produced
      an autocrine growth-stimulatory factor (AGSF) and a paracrine growth-stimulatory
      factor (PGSF). AGSF had a remarkable growth-stimulatory effect on transformed rat
      liver epithelial-cells, but had no such effect on non-transformed rat-liver
      epithelial-cells that could not proliferate in serum-free medium. AGSF did not
      show a growth-inhibitory or stimulatory effect on normal rat kidney (NRK) cells
      in monolayer culture, and did not induce anchorage-independent growth in soft
      agar culture even with epidermal growth factor (EGF) or transforming growth
      factor (TGF)-beta. AGSF was protease-sensitive, but heat- and acid-stable. The
      molecular weight was about 700 Dalton (Da) on size-exclusion chromatography. PGSF
      showed a growth-stimulatory effect on NRK cells and induced anchorage-independent
      growth in soft-agar culture without EGF or TGF-beta. On the other hand, PGSF
      slightly inhibited the growth of the spontaneously transformed rat-liver
      epithelial cells. PGSF was heat-, protease- and acid-sensitive. The molecular
      weight was 30 kDa on size-exclusion chromatography.

PMID- 1399123
TI  - Specific growth stimulation in the absence of specific cellular adhesion in lung
      colonization by retinoic-acid-treated F9 teratocarcinoma cells.
AB  - In most studies concerning organ-specific metastasis, different or selected lines
      are compared with one another. Here we report results with the same cell line
      (the F9 murine teratocarcinoma) which can be directed towards liver or lung,
      depending on whether or not it is treated with retinoic acid and cyclic AMP.
      Thus, organ-specific colonization by tail-vein-injected murine F9 teratocarcinoma
      cells shows a particular pattern: unselected, undifferentiated F9 cells
      preferentially colonize the liver of the syngeneic animal. The lungs, the first
      capillary bed encountered by cells thus injected, are only very rarely colonized.
      By contrast, the lungs become the main target organ of F9 cells induced to
      differentiate by treatment with retinoic acid and cyclic AMP. We have recently
      shown that liver colonization by undifferentiated F9 cells correlated with the
      adhesiveness of the cells (higher to fibronectin and liver-derived extracellular
      matrix than to laminin and lung-derived extracellular matrix) as well as with
      their growth response to organ-derived extracts (no response with lung extracts
      and good response with liver extracts). The data reported below indicate that
      induction of differentiation causes at most a decreased adhesiveness of F9 cells
      to all the substrata tested (laminin, fibronectin, type-IV collagen, organ
      derived extracellular matrix), suggesting that the shift in organ colonization
      observed with differentiated F9 cells is not due to an enhancement of the
      specific adhesion to the lung matrix. On the other hand, differentiated cells,
      but not undifferentiated ones, were able to respond to growth stimulation
      mediated by lung-derived extracts, thereby implying a relevant role for organ
      specific growth stimulation in lung colonization by differentiated F9 cells.

PMID- 1399125
TI  - TGF-alpha production correlates with tumorigenicity in clones of the SW613-S
      human colon carcinoma cell line.
AB  - The c-myc gene is amplified and the c-Ki-ras gene is mutated in the SW613-S human
      colon carcinoma cell line. Two cell types with different levels of c-myc
      amplification are present in the SW613-S cell population and representative cell
      clones can be isolated. The clones with a high level of amplification and
      expression of the c-myc gene are tumorigenic in nude mice whereas those with a
      low level are not. The tumorigenic clones secrete transforming growth factor
      alpha (TGF-alpha) in the culture medium whereas the non-tumorigenic clones do not
      produce any detectable amount. Accordingly the level of TGF-alpha mRNA is higher
      and the transcription rate of the gene is increased in the tumorigenic clones.
      The acquisition of the tumorigenic phenotype by cells of non-tumorigenic clones,
      following introduction of c-myc gene copies by transfection, is accompanied by an
      increase in the steady-state level of TGF-alpha mRNA. These findings suggest a
      role for an elevated level of TGF-alpha production in the tumorigenic phenotype
      of SW613-S cells. The possibility that this role is indirect is discussed.

PMID- 1399124
TI  - Activation of c-fos and c-fes in metastatic lympho-macrophage hybrids.
AB  - The expression of proto-oncogenes involved in myelomonocytic differentiation was
      studied in 3 metastatic murine lympho-macrophage hybrids (ESb, EbF1, EbF2-C4)
      which display several antigenic and functional macrophage properties.
      Constitutive expressions of fos and fesmRNA, which were not detectable in the
      weakly metastatic parent lymphoma (Eb), was shown in all the proliferating hybrid
      lines. By contrast, c-myc and c-myc expressions were shared by the tumor parent
      and the hybrids. The c-fos transcripts observed in the hybrids were atypical in
      size, 2.3 kb, but standard 2.2-kb transcripts could be detected in serum-induced
      cells, even in the non-expressing Eb lymphoma. The kinetics of the induced fos
      mRNA was found to conform to the features reported in the literature for a large
      variety of cells. No structural alteration of the c-fos gene was detected by
      Southern analysis. PCR amplification of the 2.3- and 2.2-kb fos mRNA showed that
      they are identical in size in both the coding and the 3' untranscribed region. A
      longer poly A tail is thought to account for the additional 100 bp in the 2.3-kb
      fos mRNA, as both the 2.3- and 2.2-kb transcripts attain the same size following
      de-adenylation.

PMID- 1399126
TI  - Experimental photodynamic therapy with a copper metal vapor laser in colorectal
      cancer.
AB  - In an attempt to define the best conditions for an adjunctive treatment of
      residual colonic microtumors by photodynamic therapy (PDT), an experimental model
      has been defined. S.c. HT29 colonic-cancer-cell tumors grown in nude mice were
      used and, 48 hr after i.p. administration of 30 mg/kg Photofrin (PH), laser
      illumination was performed with 75 or 150 Joules/cm2. The efficiencies of 2
      lasers, the classically used rhodamine laser (RL) and a copper metal vapor laser
      (CMVL), were compared. The effects of PDT were assessed by histological and
      immunocytochemical (detection of a digestive enzyme, dipeptidyl-peptidase IV, as
      a marker of cell viability) follow-up and by the growth curve of the tumors after
      illumination. We conclude that, although the depth of necrosis resulting from PDT
      was nearly 3 mm at 75 J/cm2 and nearly 4-5 mm at 150 J/cm2 with both lasers,
      complete necrosis was obtained only with the CMVL at 150 J/cm2 (in 50% of the
      tumors). Under the other conditions, a layer of unaffected cells persisted at the
      pole opposite to laser illumination, resulting in growth curves lower than but
      parallel to those of the controls. Analysis of drug concentrations in the tumors
      and various organs, 48 hr after injection, i.e., at the time of laser
      illumination, revealed the presence of 21 micrograms/g dry weight PH in the
      tumors. The tumor vs. host-organ ratios were equal to or higher than 1 for the
      small bowel, colon, stomach, lung, skin and muscle. In contrast, the ratios were
      below 1 for the spleen, pancreas, kidney and liver.

PMID- 1399127
TI  - Human melanoma cell-derived factor(s) stimulate fibroblast glycosaminoglycan
      synthesis.
AB  - Conditioned media from cultures of human metastatic Hs294T melanoma cells contain
      a factor/factors that promote(s) fibroblast-mediated contraction of collagen
      lattices, and stimulate(s) fibroblast glycosaminoglycan (GAG) synthesis. Complete
      medium from melanoma cell cultures stimulated fibroblast hyaluronate synthesis
      9.3-fold, and sulphated GAG synthesis 2.6-fold, as measured by 3H-glucosamine
      incorporation. 35SO4 incorporation into sulphated GAGS was essentially unaltered,
      the net result being a decrease in the degree of sulphation. Fibroblasts
      synthesized hyaluronate with an increased molecular weight when grown in the
      presence of the melanoma-cell culture medium, while the molecular weights of
      heparan and chondroitin sulphates remained essentially unaltered. Our results
      indicate that the tumour-cell-derived factor(s) stimulate(s) changes in
      fibroblast glycosaminoglycan synthesis, and that these changes may facilitate
      tumour cell invasion in vivo.

PMID- 1399128
TI  - Insulin resistance and breast-cancer risk.
AB  - Life-style has a major influence on the incidence of breast cancer. To evaluate
      the effects of life-style related metabolic-endocrine factors on breast cancer
      risk we conducted a case-control study comparing 223 women aged 38 to 75 years
      presenting with operable (stage I or II) breast cancer and 441 women of the same
      age having no breast cancer, who participated in a population-based breast cancer
      screening program. Women reporting diabetes mellitus were excluded. Sera from 110
      women of the same age group presenting with early stage melanoma, lymphoma or
      cervical cancer were used as a second 'other-cancer control group'. Serum levels
      of C-peptide were significantly higher in early breast cancer cases compared to
      controls. The same was found for the ratios C-peptide to glucose or C-peptide to
      fructosamine, indicating insulin resistance. Sex hormone binding globulin was
      inversely, triglycerides and available estradiol were positively related to C
      peptide. Serum C-peptide levels were related to body mass index (BMI), and to
      waist/hip ratio (WHR), in particular in controls. However, the relative increase
      of C-peptide, C-peptide to glucose or C-peptide to fructosamine in cases was
      independent of BMI or WHR. The log relative risk was linearly related to the log
      C-peptide levels. Relative risk according to quintiles, and adjusted for age,
      family history, BMI and WHR, for women at the 80% level was 2.9 as compared with
      those at the 20% level for C-peptide. Elevated C-peptide or C-peptide to
      fructosamine values were not observed in the sera from women belonging to the
      'other-cancer control group'. This study suggests that hyperinsulinemia with
      insulin resistance is a significant risk factor for breast cancer independent of
      general adiposity or body fat distribution.

PMID- 1399130
TI  - Characterization of a lung-cancer-associated auto-antigen.
AB  - An antigen, protein X (Px), was purified from immune complexes isolated from
      malignant pleural effusions from patients with adenocarcinoma of the lung by EDTA
      treatment, PEG 8000 precipitation, protein A affinity chromatography, and
      Sephadex G-200 separation in the presence of 3 M NaCl. The purified antigen had a
      M(r) 17,000 by SDS-PAGE, and consisted of isoelectric species of pI 6.3 and 6.6.
      Purified Px recombined with Ig isolated from pleural fluids from patients with
      lung adenocarcinoma, but not with Ig from patients with breast carcinoma. Using
      an autologous human and heterologous chicken antibody, Px was found, by
      immunohistology, in the cytoplasm of some of the well-differentiated lung
      adenocarcinoma cells, but was not seen in normal lung or a variety of other
      malignant tissues. A liquid-phase competitive-inhibition RIA was developed. Over
      30 ng/ml of Px were found in 9 of 15 pleural fluids from patients with lung
      carcinoma, none of 20 from patients with breast, ovary, stomach or colon cancer,
      and in 3 of 15 patients with unknown primary tumor. Our data suggest that Px may
      be a lung-cancer-associated autoantigen which can elicit a host humoral response
      in vivo.

PMID- 1399129
TI  - HLA-B5-restricted auto-tumor-specific cytotoxic T cells generated in mixed
      lymphocyte-tumor-cell culture.
AB  - T-cell-enriched lymphocyte populations derived from the malignant exudate of a
      patient with ovarian carcinoma were exposed to autologous tumor cells in the
      mixed lymphocyte-tumor-cell culture (MLTC) and propagated for 42 days.
      Proliferation of lymphocytes depended on exposures to autologous tumor cells and
      on the presence of IL-2. After 7 days, the MLTC-lymphocytes lysed K562 and the
      autologous tumor cells. The latter effect was not inhibited by monoclonal
      antibodies (MAbs) reactive with MHC class-I antigens or with CD3. After 7
      restimulations, the culture was enriched in CD8+ cells (92%) and showed selective
      lytic activity against the autologous tumor. This function was inhibited by the
      alpha-class I or alpha-CD3 MAbs, and also by antibodies reactive with the HLA B
      locus or B5 allele products. The antibodies reactive with HLA A molecules had no
      such effect. It seems therefore that the function of the CTLs was restricted by
      HLA B5. Analysis of the TCR beta genes indicated clonal T-cell expansion in this
      culture. This MLTC was 1 of 21 initiated with 11 blood- and 10 tumor-derived
      lymphocyte (TIL) populations prepared from the malignant effusions of ovarian
      carcinoma patients. None of these ex-vivo lymphocytes lysed autologous tumor
      cells. In 17 MLTCs the lymphocytes did not proliferate, and in 3 cultures the
      proliferation was maintained only for 2-3 weeks. In 3 of 4 cultures auto-tumor
      cytotoxicity was induced.

PMID- 1399131
TI  - Carcinogenic effect of tobacco smoking and alcohol drinking on anatomic sites of
      the oral cavity and oropharynx.
AB  - A series of 359 male patients with 424 cancer lesions of the oral cavity and
      oropharynx identified at a US Department of Veterans Affairs Medical Center were
      divided according to site of origin of the lesion and compared with 2,280
      controls from the same hospital with respect to exposure to tobacco smoking and
      alcohol drinking. Sites of origin were: floor of the mouth (153), oral tongue
      (50), anterior tonsillar pillar (49), soft palate (44), lingual aspect of
      retromolar trigone (11), alveolar ridge (5), buccal mucosa (4), and hard palate
      (2). Forty-one patients had cancers in multiple sites. Tobacco smoking was more
      strongly associated with soft-palate lesions than with lesions in more anterior
      sites. Patients with cancer of floor of the mouth and oral tongue had higher odds
      ratios for alcohol drinking than subjects with cancers of other sites. This study
      supports the hypothesis of the carcinogenic effect of tobacco smoke and alcoholic
      beverages on the oral mucosa through direct contact.

PMID- 1399132
TI  - Expression of the matrix Gla protein in urogenital malignancies.
AB  - Matrix Gla protein (MGP), is a vitamin-K-dependent protein which is synthesized
      in a variety of tissues such as lung, heart, kidney, cartilage and bone. The
      function of MGP in these tissues is unclear. We have previously reported elevated
      MGP mRNA levels in a breast-cancer cell line, 600PEI, as compared to normal
      breast epithelium. Here we describe high MGP expression in primary renal-cell
      carcinomas, prostate carcinomas and testicular germ-cell tumors, as determined by
      Northern analysis. MGP was over-expressed in 21 out of 28 patients with renal
      cell carcinoma, and in 16 out of 29 patients with testicular germ-cell tumors, as
      compared to matched normal tissues. For the renal-cell carcinomas, a
      statistically significant inverse correlation was observed between the level of
      MGP expression and tumor size, lymph-node metastasis and tumor grade. MGP was
      also highly expressed in 13 primary prostatic carcinomas as compared to prostate
      cell lines derived from metastatic tumors, and to lymph-node metastasis. Our
      findings indicate that the loss of MGP expression may be associated wih tumor
      progression and metastasis.

PMID- 1399133
TI  - International variations in the incidence of neuroblastoma.
AB  - The International Agency for Research on Cancer has coordinated a worldwide study
      of childhood cancer incidence, with data from over 50 countries. We present here
      the results for neuroblastoma. In predominantly white Caucasian populations the
      age-standardized rate was 7-12 per million, and 6-10% of all childhood cancers
      were neuroblastomas. Rates were highest in the first year of life (25-50 per
      million, 30% of total neuroblastoma incidence), and decreased with age to 15-20
      per million (50% of the total) at age 1-4, 2-4 per million (15%) at 5-9 and 1-1.5
      per million (5%) at 10-14. In the United States, black children had an incidence
      of 8.5 per million compared with 11.5 among Whites; Blacks tended to be older
      than Whites at diagnosis. The highest rate in Africa was in Bulawayo, Zimbabwe
      (8.0 per million) and the lowest in West Nile, Uganda, with no cases registered.
      Incidence in Israel was similar to that in many white populations, with Jews
      having a particularly high rate. In other parts of West Asia neuroblastoma had a
      low relative frequency, suggesting that incidence is low. Rates were also low
      throughout much of southern and eastern Asia, including India and China.
      Incidence in Japan was somewhat higher, though less than in Western countries,
      with the deficit most pronounced in the first year of life; these data relate to
      the period before mass screening of infants for neuroblastoma in the regions
      concerned. Incidence was generally higher in regions and among ethnic groups
      enjoying a higher standard of living, though previous studies within single
      countries had suggested that neuroblastoma is more common among less affluent
      groups. Blacks in Africa and the United States may have a weaker genetic
      predisposition to neuroblastoma, but some of the deficit in many developing
      countries is likely to be due to under-diagnosis.

PMID- 1399134
TI  - PCR assay for chromosome 1p deletion in small neuroblastoma samples.
AB  - Deletion of the short arm of chromosome 1 is among the most recurrent cytogenetic
      alterations found in neuroblastoma and has been associated with short survival.
      However, this prognostic information, which relies on time-consuming techniques,
      is not yet routinely exploited. In order to set up a reliable and simple routine
      test to determine 1p deletion in neuroblastoma, we have used the polymerase chain
      reaction to genotype neuroblastoma DNA at 2 loci containing a variable number of
      tandem repeats and located on the distal part of the short arm of chromosome 1.
      Agarose gel electrophoresis and ethidium bromide staining of the amplification
      products enable a simple determination of constitutional and tumor genotypes at
      these loci to be made. A total of 37 samples from 29 patients were studied with
      this technique. Loss of heterozygosity (LOH) could be identified in 8 cases. In
      each case the results obtained were in agreement with those achieved by the
      Southern procedure. This technique will be of particular interest in the
      pretherapeutic analysis of 1p deletions in small tumor samples obtained by fine
      needle aspirates of the primary tumor. It should also enable retrospective
      studies from paraffin-embedded tumor fragments to be made and provide information
      for the analysis of tumor heterogeneity in neuroblastoma and in other tumors with
      1p deletions.

PMID- 1399135
TI  - Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the
      United States.
AB  - Population-based incidence data on nasopharyngeal carcinomas (NPC) from the
      Surveillance, Epidemiology and End Results program in the United States were
      examined for the years 1973-1986. The 1,645 cases showed incidence rates varying
      according to ethnic origin, with chinese having the highest, followed by
      Filipinos, Blacks and Whites. In females the incidence was about half of that
      seen in males, in each of these groups. There was no evidence of changes in
      incidence rates during the study period. An analysis of survival with NPC was
      undertaken using hazard function regression models to allow for control of
      multiple variables. Survival was found to be independently influenced by age and
      stage at diagnosis, histologic type, grade and sex. Significant ethnic
      differences in survival remained after adjustment for these factors, with Chinese
      surviving longest followed by Filipinos, Whites and Blacks. These difference in
      survival remained after control for the variation in population-wide mortality
      rates associated with age, ethnicity, sex and calendar year. We present evidence
      that survival has improved for this disease over time.

PMID- 1399136
TI  - A population-based case-control study of cancers of the nasal cavity and
      paranasal sinuses in Shanghai.
AB  - A population-based case-control study of cancer of the nasal cavity and sinuses,
      involving interviews of 60 incident cases and 414 controls, was conducted in
      Shanghai. Cigarette smoking was associated with a mild elevation in risk of
      squamous-cell carcinoma but not cancers of other cell types. Occupational
      exposures to wood and silica dusts and to petroleum products, and the use of wood
      and straw as cooking fuel, were linked to moderate increases in risk, while 4
      fold or greater increases were associated with a history of chronic nasal
      diseases, including those occurring 10 or more years prior to cancer diagnosis.
      Dietary analyses revealed a significant protective effect of consumption of
      allium vegetables, oranges and tangerines, with a 50% reduced risk of nasal
      cancer among individuals in the highest intake group of these foods. Consumption
      of salt-preserved vegetables, meat and fish was associated with a significantly
      increased risk of nasal cancer in a dose-response fashion, with a 5-fold excess
      observed for the heaviest intake of these salted foods. These findings suggest
      that dietary factors may contribute to the development of nasal cancer.

PMID- 1399137
TI  - Risk factors for renal-cell cancer in Shanghai, China.
AB  - A population-based case-control study of 154 histologically verified renal-cell
      cancer patients and 157 controls was performed in Shanghai, China, an area with
      low rates for this tumor. Elevated risks were observed for cigarette smoking
      (odds ratio (OR) = 2.3; 95% confidence interval (CI): 1.1 to 4.9), and for
      increasing categories of body weight and meat consumption, while reduced risks
      were seen for increasing categories of fruit and vegetable intake. An increased
      risk was also observed for regular use of phenacetin-containing analgesics (OR =
      2.3; 95% CI:0.7 to 7.0). These findings are consistent with earlier studies in
      Western countries, and indicate that many of the same etiologic factors for renal
      cell cancer operate in low- and high-risk societies.

PMID- 1399138
TI  - Effect of smoking on folate levels in buccal mucosal cells.
AB  - The objective of the study was to document the existence of localized deficiency
      of folate in a tissue exposed to cigarette smoke, by analysis of oral and
      circulatory levels of this vitamin in smokers and non-smokers. Buccal mucosal
      cells and blood samples were collected from 25 smokers and 34 non-smokers. The
      Health Habits and History Questionnaire was completed by each subject. A 96-well
      plate L. casei assay, along with preincubation with a folate-free chick pancreas
      pteroyl-gamma-glutamyl hydrolase, was used to quantitate total buccal mucosal
      cell folates. The reproducibility (CV 5 to 7%) and recovery (95 to 106%) of the
      folate assay were satisfactory. Smokers had significantly lower buccal mucosal
      cell folate levels than did non-smokers. The mean plasma folate level of smokers
      although within normal limits, was also significantly lower than that of non
      smokers. There were no significant differences in mean dietary folate intake or
      in alcohol consumption between the 2 groups. The strength of the positive
      association between smoking and plasma and buccal mucosal cell folate deficiency
      (by any definition) was moderate to strong and statistically significant. Our
      results indicate that cigarette smoking may result in a localized folate
      deficiency in buccal mucosal cells, independent of the plasma folate levels.

PMID- 1399139
TI  - Frequent loss of heterozygosity on chromosomes Xp and 13q in human ovarian
      cancer.
AB  - Loss of heterozygosity (LOH) was examined at 27 loci on chromosomes 3p, 6q, 11p,
      13q, 17 and X in 42 human ovarian tumors. LOH was detected in 12 of 26 (46%) and
      5 of 12 (42%) informative cases at 2 chromosome 13q loci, D13S32 and D13S34
      respectively. On chromosome Xp, tumor-specific allele loss was observed in 9 out
      of 15 informative cases (60%) at the ornithine transcarbamylase (OTC) gene locus.
      Examination of 12 additional Xp and 13q loci has mapped the common deletion
      regions to Xp21.1-->p11.4 and 13q33-->q34. The observation of significant LOH on
      Xp represents a strong indication of genetic changes in the X chromosome in a
      human malignancy. The allele losses on 13q which have been reported for other
      cancers suggest that chromosome 13, in addition to the retinoblastoma gene, may
      contain other growth-regulating gene(s) important in the development of several
      tumor types, including ovarian malignancies.

PMID- 1399140
TI  - Immunohistochemical determination of androgen receptors in relation to oestrogen
      and progesterone receptors in female breast cancer.
AB  - The expression of oestrogen (ER), progesterone (PR) and androgen (AR) receptors
      in female breast cancer was investigated by immunohistochemistry on snap-frozen
      tissue specimens of a series of 100 breast cancers. For detection of the AR we
      used a recently developed mouse monoclonal antibody specific for the N-terminal
      domain of the human AR. Expression of AR was compared with that of ER and PR as
      well as with tumour grade and age. Of the breast cancers investigated, 76% were
      AR-positive. This high percentage corresponds well with previous data on AR
      expression in breast cancer determined with ligand-binding assays. In 53% of the
      tumours AR, ER and PR were present, while 9% of the tumours were positive for AR
      and negative for ER and PR. In 13% of the tumours no ER, PR or AR expression was
      seen; these were all grade-III tumours. A positive correlation was found between
      age and ER expression, but no correlation was seen between age and PR or AR.
      Future studies should establish the prognostic value of the combination ER, PR
      and AR determinations on female breast cancer with regard to biological behaviour
      and response rate to hormonal therapy.

PMID- 1399141
TI  - The gene encoding for MC56 determinant (drug-sensitivity marker) is located on
      the short arm of human chromosome 11.
AB  - A panel of mouse x human B- and T-cell hybrids was analyzed for the expression of
      MC56 determinant which marks the drug-sensitive state of CEM cells. Karyotypic
      and phenotypic analyses of the tested clones showed that the expression of MC56
      determinant correlated to the presence of human chromosome 11 and segregated
      concordantly to the epitopes recognized by monoclonal antibodies in the CD44
      cluster. By using a particular class of interspecific rodent x human-cell hybrids
      in which the human genome counterpart is represented in the different clones only
      by human chromosome 11 or its fragments, we showed that the gene encoding for
      MC56 determinant is located on the region p13-pter of the short arm of chromosome
      11. Therefore, the hypothesized homology between the drug-sensitivity marker MC56
      and the CD44 determinant is supported also by gene mapping studies.

PMID- 1399142
TI  - Characterization of a mouse-human chimeric antibody to a cancer-associated
      antigen.
AB  - In an attempt to obtain a therapeutic antibody, the murine monoclonal antibody
      (MAb) MBrI (IgM,k), directed against human carcinomas, was converted in a
      mouse/human chimeric MAb of gamma I isotype. The chimeric MAb, gamma I CHI-MBrI,
      retains the ability to specifically bind tumor cells and tissues with no
      modification in its binding to the normal material tested. gamma I CHI-MBrI
      recognizes mucins and high-molecular-weight glycoproteins carrying the antigenic
      determinant and stains a neutral glycolipid extracted from MCF-7 cells. The
      chimeric and the murine MBrI efficiently cross-inhibit each other on the
      reference cell line MCF-7 and the calculated affinity constants amount to 3.8 x
      10(7) and 1.7 x 10(8) M-1, respectively. The human constant region allows gamma I
      CHI-MBrI to bind with the FcR on the human monocytic cell line U937 and to
      efficiently mediate antibody-dependent cellular cytotoxicity in the presence of
      human lymphocytes activated by IL2. In addition, gamma I CHI-MBrI, like the
      murine MBrI, mediates complement-dependent tumor-cell lysis. Thus, by modelling a
      molecule with reduced size and increased functional characteristics, we have
      obtained a reagent which is more suitable for in vivo therapeutic approaches.

PMID- 1399143
TI  - The lipoxygenase metabolite 12(S)-HETE promotes alpha IIb beta 3 integrin
      mediated tumor-cell spreading on fibronectin.
AB  - Tumor-cell interaction with the vessel wall during metastasis involves adhesion,
      induction of endothelial-cell retraction and spreading on the exposed sub
      endothelial matrix. The signals for initiation of tumor-cell spreading and the
      receptors involved are unknown. A protocol was developed to distinguish between
      initial tumor-cell (B16 amelanotic melanoma; B16a) adhesion to and spreading on
      fibronectin. The time for maximum spreading was 50 min. Treatment with a
      lipoxygenase metabolite of arachidonic acid [12(S)-HETE] resulted in maximum
      spreading in 15 min (max. effect approx. 0.1 microM). Other lipoxygenase
      metabolites were ineffective. 12(S)-HETE treatment induced a rearrangement of F
      actin, vinculin, vimentin intermediate filaments and integrin alpha IIb beta 3,
      but not integrin alpha 5 beta 1. Antibodies to alpha IIb beta 3 but not alpha 5
      beta 1 blocked the 12(S)-HETE effect on B16a spreading. B16a-cell attachment to
      fibronectin resulted in increased metabolism of arachidonic acid to 12(S)-HETE,
      which was inhibited by lipoxygenase but not by cyclo-oxygenase inhibitors.
      Accordingly, lipoxygenase inhibitors but not cyclo-oxygenase inhibitors blocked
      spontaneous B16a-cell spreading. The protein-kinase-C inhibitors calphostin C, H7
      and staurosporine also inhibited spreading, while the protein-kinase-A inhibitor
      H8 was ineffective. These data suggest that B16a-cell spreading on fibronectin is
      initiated by a lipoxygenase metabolite [12(S)-HETE] of arachidonic acid and is
      mediated by protein kinase C.

PMID- 1399144
TI  - Involvement of histo-blood-group antigens in the susceptibility of colon
      carcinoma cells to natural killer-mediated cytotoxicity.
AB  - The susceptibility to natural-killer-cell lysis and expression of histo-blood
      group antigens of 2 clones from a rat colon adenocarcinoma, of variants derived
      from them and of 17 human colon carcinoma cell lines were assessed in an attempt
      to determine if the major glycosidic tissue antigens of epithelial cells could
      influence the NK susceptibility of tumor target cells of epithelial origin. The
      rat REGb clone, which is relatively NK-sensitive, expressed higher levels of
      precursor structures T and Tn and lower levels of H antigenic determinants than
      the PROb clone, which displays higher resistance to NK-cell lysis. Cell variants
      were obtained from these 2 clones; it appeared that whether the cell variants
      were selected on the basis of expression of a blood-group antigenic determinant
      or on the basis of altered susceptibility to NK-cell lysis, there was a link
      between increased resistance and higher expression of cell-surface A and H histo
      blood-group antigens, or conversely, between increased sensitivity and higher
      expression of precursor structures. Similar conclusions were obtained upon study
      of the human cell lines, since a significant correlation was found between the
      level of expression of T or Tn antigens and sensitivity to NK-cell lysis. A
      significant relationship was found between the expression of Lewis antigens and
      increased resistance to NK-cell-mediated cytotoxicity.

PMID- 1399145
TI  - Cytotoxicity of a transferrin-adriamycin conjugate to anthracycline-resistant
      cells.
AB  - Conjugates of adriamycin coupled to transferrin by glutaraldehyde are cytotoxic
      to human promyelocytic (HL-60) and erythroleukemic (K562) cells. Growth
      inhibition of adriamycin-sensitive cells, as evaluated by thymidine incorporation
      and the MTT-assay, was higher for conjugates than for free adriamycin. The
      cytotoxicity toward adriamycin-resistant K562 and HL-60 cells was 3-fold and more
      than 10-fold higher, respectively, for the transferrin-adriamycin conjugate than
      for the free drug. The effect of the conjugate was dependent on its adriamycin
      content, i.e., on its conjugation number.

PMID- 1399146
TI  - Immunotoxins directed against the high-molecular-weight melanoma-associated
      antigen. Identification of potent antibody-toxin combinations.
AB  - To study factors influencing the cytotoxicity of immunotoxins (ITs), we compared
      the in vitro cytotoxicity of conjugates in which the plant toxin abrin and the
      bacterial toxin Pseudomonas exotoxin A (PE) were coupled by 2 different
      procedures to 2 MAbs, 9.2.27 and NR-ML-05, which bind to different epitopes on
      the melanoma-associated antigen p250. The individual target cell lines differed
      widely in sensitivity to the different ITs, as assessed by measurement of protein
      synthesis inhibition. The action of the ITs was highly specific, as the toxicity
      of abrin and PE conjugates was respectively 20-540 and 2,200-550,000 times higher
      in antigen-positive cell lines (FEMX, SESX, OHS) than in the antigen-negative
      line KPDX. The PE conjugates prepared with the 2 different MAbs differed in
      potency by factors of 16-126 in the target-cell lines, but were consistently more
      toxic than the abrin ITs. The results demonstrate that the cytotoxicity of ITs
      varies with the nature of both of its moieties and that optimal results require
      that toxins and MAbs be matched. Moreover, the 2 coupling procedures affected
      differentially the binding and potency of some ITs. Each of the 2 toxins was
      conjugated to a sheep anti-mouse antibody (SAM) and the toxicity of these 2
      conjugates was tested in an indirect approach using 9.2.27 and NR-ML-05 as
      primary MAbs. The results showed that the indirect procedure would have correctly
      predicted the most potent antibody-toxin pair, indicating that the approach may
      be valid for selecting suitable combinations of MAbs and toxins for use as direct
      ITs.

PMID- 1399147
TI  - Cystatin C and cathepsin B in human colon carcinoma: expression by cell lines and
      matrix degradation.
AB  - Expression of the cysteine proteinase cathepsin B and its physiological inhibitor
      cystatin C was analyzed in vitro in 1 human fibrosarcoma and 4 human colon
      carcinoma cell lines. Cystatin C antigen as well as cathepsin B activity were
      detected in the conditioned media of the 5 cell lines. The corresponding cell
      extracts expressed high levels of cathepsin B activity, whereas only trace
      amounts of cystatin C antigen could be found. Northern-blot analysis revealed the
      presence in the 5 cell lines of a 0.8-kb cystatin C mRNA transcript and 2
      cathepsin B transcripts of 2.3 and 4.3 kb. Pepsin treatment of tumor-cell
      released cathepsin B induced an average 7.3-fold increase in activity, indicating
      that the enzyme was mainly present as a latent form in conditioned medium. The
      pepsin-activated cathepsin B from one colon carcinoma cell line was further
      characterized using the cysteine proteinase inhibitors E-64, recombinant cystatin
      C, a cystatin-C-derived peptidyl inhibitor (Z-LVG-CHN2), and cathepsin-B-specific
      diazomethyl ketone inhibitors (Z-FT(OBzl)-CHN2, Z-FS(OBzl)-CHN2). This activity
      was totally neutralized by recombinant cystatin C, suggesting a potential for
      interaction between released extracellular cathepsin B and cystatin C. In vitro
      assays of degradation of extracellular matrix showed that cysteine proteinase
      inhibitors could decrease matrix degradation induced by pepsin-activated
      conditioned media. With colon cells, this inhibition was not observed, indicating
      a requirement for an extracellular activation of latent cathepsin B. Our data
      provide evidence that cystatin C and latent cathepsin B are both released
      extracellularly by colon carcinoma cells in vitro. They suggest that cystatin C
      and cathepsin B interactions may participate, in an as yet unelucidated way, in
      the modulation of the invasive phenotype of human colonic tumors.

PMID- 1399148
TI  - Genes involved in tumor invasion and metastasis are differentially modulated by
      estradiol and progestin in human breast-cancer cells.
AB  - Invasion of basement membranes by cancer cells is a critical step in metastasis,
      which requires the coordinated expression of specific genes such as laminin
      receptors and metalloproteinases. Estradiol and progesterone modulate the
      clinical progression of steroid-sensitive breast cancers; however, little is
      known about the molecular regulation of the invasive phenotype by these hormones.
      We therefore examined the effects of 10 nM estradiol and/or 10 nM progestin R5020
      on the expression of 2 non-integrin laminin binding proteins, the 67-kDa laminin
      receptor (67LR) and HLBP31 as well as the 72-kDa type-IV collagenase (MMP-2) and
      its inhibitor, TIMP-2, in steroid-receptor-positive (T47D and MCF-7) and 
      negative (MDA-MB 231) human breast-cancer cells. The relative steady-state level
      of 67LR mRNA was increased 2- to 3-fold by estradiol in both MCF-7 (p < 0.001)
      and T47D (p < 0.001) cells, also by R5020, alone or in combination with
      estradiol, in T47D cells (p < 0.001) and to a much less extent in MCF-7 cells.
      HLBP31 mRNA and protein levels were increased 2- to 3-fold (p < 0.001) by R5020
      alone or in combination with estradiol, but not by estradiol alone. None of the
      steroid treatments affected the expression or activity of MMP-2. Interestingly,
      however, TIMP-2 mRNA levels and protein expression in MCF-7 and T47D cells were
      50% down-regulated (p < 0.001) by treatment with R5020 or R5020 plus estradiol,
      but not by treatment with estradiol alone. None of these genes were modulated in
      steroid-independent MDA-MB231 cells. The data suggest that estradiol and
      progesterone might act as coordinators regulating specific genes in the steroid
      sensitive breast-cancer cell, leading to the acquisition of the metastatic
      phenotype.

PMID- 1399149
TI  - Phosphoprotein B23 translocation and modulation of actinomycin D and doxorubicin
      cytotoxicity by dipyridamole in HeLa cells.
AB  - During continuous exposure, cells were more responsive to doxorubicin (DOX) in
      the presence of dipyridamole (DPM). Translocation of nucleolar phosphoprotein B23
      and inhibition of cell growth occurred with a lower dose of DOX and in a shorter
      incubation time in the presence of DPM. DPM did not change translocation induced
      by actinomycin D (Act-D). Short exposure of HeLa cells to Act-D induced
      "reversible" translocation of protein B23 as well as "reversible" inhibition of
      cell growth. DPM included in the cell culture after removal of Act-D inhibited
      the recovery of cell growth as well as the corresponding relocalization of
      protein B23 from the nucleoplasm to nucleoli. DPM administered in the fresh
      medium after 30 min exposure to DOX had little effect on the potentiation of the
      induced translocation of protein B23 and inhibition of cell growth. Our results
      indicated that "B23 translocation" is closely associated with states of cell
      growth. The potentiation of the inhibition of cell growth by DPM is associated
      with the extent of enhanced protein B23 translocation. "B23 translocation" may
      therefore be a simple and rapid method for assessing the inhibition of cell
      growth and for determining the efficacy of combination cancer chemotherapy.

PMID- 1399150
TI  - The presence of concanavalin-A(Con-A)-like molecules on natural-killer (NK)
      sensitive target cells: their possible role in swainsonine-augmented human NK
      cytotoxicity.
AB  - In the present study we examined the expression of concanavalin-A(Con-A)-like
      molecules on natural-killer (NK)-sensitive target cells and investigated their
      possible role in the human NK-cell phenomenon. The incubation of either
      peripheral-blood lymphocytes (PBL) or large granular lymphocytes (LGL) with
      swainsonine (SW), an inhibitor of mannosidase II, resulted in the augmentation of
      cytotoxicity against K562 leukemia cells. The enhanced cytotoxicity was
      associated with increased binding of fluorescein isothiocyanate-conjugated Con-A
      to SW-treated effector cells, and immunofluorescence staining of the target K562
      cells using goat anti-Con-A antibody (Ab) showed a significant positive shift in
      the flow cytometric pattern. Electrophoretic separation and immunoblotting
      analysis revealed that 4 components with a molecular weight of approximately 95,
      80, 60 and 50 kDa were recognized by anti-Con-A Ab from the detergent-extract of
      K562 cells. The addition of Con-A during the antibody incubation step of the
      Western blotting abolished their expression, thus excluding non-specific binding
      of the antibody. The addition of Con-A also strongly inhibited the cytotoxicity
      of SW-treated effector cells (PBL or LGL) against K562 cells, and this inhibition
      was abolished by 40 mM alpha-methyl-mannopyranoside (alpha-MM), which binds to
      Con-A. Furthermore, Con-A increased the binding frequency of SW-treated LGL to
      K562, in spite of the inhibited cytotoxicity, and this effect could be
      neutralized by the further addition of alpha-MM. Our results suggest that Con A
      like molecules might play an important role in cell-cell interactions between SW
      treated effector cells and NK target cells.

PMID- 1399151
TI  - Lethal midline granuloma in Seoul (Korea) and Shanghai (China)

PMID- 1399152
TI  - Inadvertent hypnosis during interrogation: false confession due to dissociative
      state; mis-identified multiple personality and the Satanic cult hypothesis.
AB  - Induction of a dissociative state followed by suggestion during interrogation
      caused a suspect to develop pseudo-memories of raping his daughters and of
      participation in a baby-murdering Satanic cult. The pseudo-memories coupled with
      influence from authority figures convinced him of his guilt for 6 months. During
      this time, the suspect, the witnesses, and all the evidence in the case were
      studied. No evidence supported an inference of guilt and substantial evidence
      supported the conclusion that no crime had been committed. An experiment
      demonstrated the suspect's extreme suggestibility. The conclusion reached was
      that the cult did not exist and the suspect's confessions were coerced
      internalized false confessions. During the investigation, 2 psychologists
      diagnosed the suspect as suffering from a dissociative disorder similar to
      multiple personality. Both psychologists were predisposed to find Satanic cult
      activity. Each concluded that the disorder was due to "programming" by the non
      existent Satanic cult.

PMID- 1399153
TI  - Effects of "deepening" techniques on hypnotic depth and responding.
AB  - The present study attempted to assess the effectiveness of commonly used
      deepening techniques and of surreptitiously provided stimulation on
      hypnotizability scores, in-hypnosis depth reports, retrospective realness
      ratings, and the Field Inventory of Hypnotic Depth (Field, 1965). High, medium,
      and low hypnotizables were assigned in equal numbers to 1 of 3 groups, each
      containing 54 Ss. Controls were compared to Ss receiving 2 deepening techniques
      or 2 suggestions for positive and negative hallucinations that were
      surreptitiously enhanced. Of the 4 dependent measures employed, the only
      significant difference between groups related to a change in depth reports for
      the manipulation items themselves, leading to the conclusion that the effect of
      the techniques was at best minimal and transient. Some methodological and
      conceptual issues are also discussed.

PMID- 1399154
TI  - Prospective time estimation and hypnotizability in a simulator design.
AB  - The present study of prospective time estimation examined the effects of hypnosis
      on short time intervals using a real-simulator design. The major hypothesis
      predicted a 2-way interaction between group (high hypnotizable, low hypnotizable,
      and simulator) and condition (waking and hypnotic) across all 4 time intervals
      (30, 60, 120, and 240 seconds). It was further hypothesized that on a "suggested"
      task (a measure of hypnotic depth), high hypnotizable Ss and simulators would not
      differ from each other but would differ from low hypnotizable Ss. 42
      undergraduates were screened on both the Creative Imagination Scale (Wilson &
      Barber, 1977) and the Stanford Hypnotic Clinical Scale for Adults (Morgan & J. R.
      Hilgard, 1975, 1979) and assigned to 1 of 3 groups (high hypnotizable, low
      hypnotizable, simulator) based on combined hypnotizability scores. Ss verbally
      estimated time intervals of 30, 60, 120, and 240 seconds, 3 times each, both
      while in a waking and a hypnotic condition. Hypnotic depth was assessed once
      following each time interval. Partial support was found for the first hypothesis
      where, for both the 60- and 120-second intervals, high hypnotizable Ss increased
      their overestimation in the hypnotic condition. Low hypnotizable and simulator Ss
      showed no such increase. The second hypothesis, that high hypnotizable and
      simulator Ss would differ from low hypnotizables on the "suggested" task, was
      confirmed. The partial replication of previous research was examined in the
      context of choice of hypnotizability measure and reliability of time estimation.

PMID- 1399155
TI  - Experience of peripheral temperature change during hypnotic analgesia.
AB  - Many Ss who experience hypnotic analgesia in a portion of their body often report
      that it is accompanied by sensations of coldness in the affected area.
      Experiments were conducted to determine if such reports are the result of a
      physical change in peripheral temperature or are due to psychological factors.
      When analgesia was induced in a limb or in the back of the neck, a concomitant
      physical change in temperature was not observed. Ss did report experiencing
      coldness, however, in the affected body part. Such experiences were attributed to
      associations that Ss developed between numbness or analgesia and a drop in
      peripheral temperature. As a result, coldness as an associate of hypnotic
      analgesia is suggested as a manipulation check for the presence of such sensation
      reduction.

PMID- 1399156
TI  - Smokeless tobacco consumption in Grant County, New Mexico.
AB  - A telephone survey was conducted in order to assess the prevalence of smokeless
      tobacco consumption in Grant County, New Mexico. Systematic random sampling was
      used, and 1 out of 25 phone numbers were selected from the county telephone
      directory. One hundred seventy-eight respondents were surveyed. Thirty-three
      percent of 96 males and 7% of 82 females identified themselves as smokeless
      tobacco users.

PMID- 1399157
TI  - Psychosocial consequences of alcohol misuse in the family of origin.

PMID- 1399158
TI  - Perceptions of drinking problems among undergraduate students in the United
      States and Scotland.
AB  - This study compares the perceptions of problem drinking and preferred
      explanations for problem drinking held by 440 undergraduate students in the
      United States and 185 in Scotland. Respondents' drinking habits influenced
      perceptions of drinking problems in both nations. The Scottish sample, with
      drinking habits statistically controlled, was less likely to perceive drinking
      problems than the United States sample and was less likely to endorse a
      physiological explanation for drinking problems. The importance of different
      perceptions in influencing decisions to seek help is discussed.

PMID- 1399159
TI  - Conscious and unconscious perceptions of self in children of alcoholics.
AB  - The conscious and unconscious self-concept was examined in three groups of
      children: 23 children of alcoholics (COA), 19 children from nonalcoholic but
      dysfunctional families, and 23 children from normal families without alcoholism
      or family dysfunction. Self-concept was assessed both objectively, using the
      Piers-Harris Children's Self Concept Scale, and subjectively, using the Draw-A
      Person Test and the Thematic Apperception Test from rating systems designed to
      tap unconscious dimensions of self. The COAs and normal controls were also
      compared for behavioral problems with the Achenbach Child Behavior Checklist. We
      found that COAs made more positive self-statements on objective measures of self
      concept than children from families without alcoholism, whether or not the
      families were dysfunctional. Subjective analyses of projective test responses
      revealed unconscious differences in self-concept among the COAs, though this was
      not corroborated with objective scores, probably due to the crudeness of the
      rating instrument in failing to tap these dimensions. Also COAs had significantly
      more behavior problems, based on parental reports, which contrasts with their
      objective reports of self. Implications of these findings were discussed.

PMID- 1399161
TI  - Young heavy drinkers and their drinking experiences: predictors of later alcohol
      use.
AB  - This study illustrated the impact of late adolescent and young adult alcohol
      experiences on current level of alcohol use. Additional factors investigated
      include reported age of problem onset, initial age of alcohol use, marital
      status, and life-span risk-taking behavior. A stepwise discriminant analysis was
      used to determine the importance of various subtypes of drinking experiences and
      combinations of these subtypes. Correct classification of current light and heavy
      alcohol drinkers by use of these experiences was 83.7% for late adolescent
      experiences and 77.5% for young adulthood experiences. The results suggest that
      early drinking experiences are useful predictors of future drinking patterns.

PMID- 1399160
TI  - Family structure and adolescent risk-taking behavior: a comparison of Mexican,
      Cuban, and Puerto Rican Americans.
AB  - We use the Hispanic HANES to examine whether family structure is related to
      alcohol and drug use among Mexican, Puerto Rican, and Cuban American adolescents.
      Mexicans adolescents living in female headed households have higher rates of
      drinking, drug use, and overall risk-taking behaviors than those living with both
      parents. Puerto Ricans adolescents living in female-headed households have higher
      rates of overall risk-taking behaviors than those living with both parents.
      Family structure is unrelated to Cuban adolescent risk-taking behavior. There is
      no evidence that gender modifies the effect of family structure for adolescent
      risk-taking behaviors.

PMID- 1399162
TI  - Recommendations for improving drug treatment.
AB  - Recognizing that drug use is both chronic and relapsing once an individual is
      addicted, and that treatment is effective in reducing drug use/misuse, improving
      drug misuse treatment is examined and research as well as practice
      recommendations are presented. Drug misuse treatment is now recognized in the
      United States to meet the expanding drug use problem and for reducing the spread
      of HIV. With that background, the current status of drug misuse treatment is
      reviewed, clinical issues are emphasized, and policy issues are noted.
      Recommendations include the need for uniform funding, linkage with community
      agencies, technology transfer, training, and expanding research and evaluation
      efforts.

PMID- 1399163
TI  - NIAAA and the new epidemiology.

PMID- 1399164
TI  - The role of significant life events in discriminating help-seeking among illicit
      drug users.
AB  - This paper examines the role of significant life events in distinguishing two
      samples of illicit drug users: 120 help-seekers (the "agency group") and 120 not
      seeking help (the "non-agency group"). We examined 10 life areas clustered around
      the general categories of "substance use," "social functioning," and "emotional
      and interpersonal functioning." A range of objective and self-reported
      information was collected regarding each life area covering the 12 months prior
      to interview. Analysis revealed that the agency group experienced a greater
      number of negatively perceived drug-related life events than the non-agency
      group. These life events were also more likely to have occurred in recent months,
      prompting reported "concern" and "need for help" among the agency group.
      Additionally, length of use of current primary drug was seen to be a contributory
      variable in distinguishing between the groups.

PMID- 1399165
TI  - Acculturation, alcohol consumption, and casualties among United States Hispanics
      in the emergency room.
AB  - The association of alcohol consumption and casualties was analyzed among Hispanic
      emergency room patients to determine whether level of acculturation and
      accompanying changes in drinking patterns influence risk of alcohol-related
      injuries. A sample of patients admitted to a county hospital emergency room
      during a 1-year period was breathalyzed and interviewed (N = 1,102). Of these,
      112 identified themselves as Hispanic. Hispanic males were more likely than non
      Hispanics to have positive breathalyzer readings, to report drinking prior to the
      event, and to attribute a causal association of drinking with the event. These
      findings were most pronounced among those in the moderate and high acculturation
      groups.

PMID- 1399166
TI  - Relationships between mood around slip-up and recovery of abstinence in smoking
      cessation attempts.
AB  - Data are presented from 201 slip-up episodes in attempts at smoking cessation.
      Analysis as a function of whether the person recovered and resumed abstinence
      broadly confirmed previous findings. Emotions immediately before and after the
      slip-up episode were assessed, as were feelings about having slipped-up. Feeling
      bad prior to the slip-up cigarette was associated with reduced recovery. By
      contrast, reporting that the slip-up cigarette made the person feel worse was
      associated with increased recovery. Feeling bad about slipping-up was not
      associated with relapse, contrary to predictions from Marlatt and Gordon's
      theorizing about the Abstinence Violation Effect.

PMID- 1399167
TI  - The prediction of long-term outcome of male alcoholics after inpatient treatment:
      the case of a clinical population in German-speaking Switzerland.
AB  - 373 out of 497 patients treated between 1975 and 1984 in a Swiss clinic for male
      alcoholics could be traced for a follow-up study in 1988. Of these, 24% died
      between the time of leaving the clinic and the time of the interview. Among the
      survivors, almost 50% reported abstinence for at least the last 12 months.
      However, 132 (26%) of the former patients could not be traced. In many studies
      the majority of those lost cases are supposed to have died or to be unremitted,
      thus the effective results of the follow-up study are supposed to be less
      favorable had those cases been traced. In order to clarify this hypothesis, a
      discriminant analysis was performed to designate the actual life status/drinking
      status of those unknown cases using sociodemographic and drinking-style data of
      the statistical records of the clinic as independent (predictor) variables. The
      results show that the number of survivors among the untraced cases is estimated
      to be equal to those traced. However, the number of problem drinkers among the
      survivors is estimated to be higher amid the untraced than among those
      interviewed in the follow-up.

PMID- 1399168
TI  - A case-control study of risk factors of alcohol misuse in Czech women: are there
      four types of female alcoholism?
AB  - Three samples of Prague women aged 20-49 were interviewed with regard to
      hypothetical risk factors of alcoholism: 139 inpatients diagnosed as alcohol
      dependent, 39 inebriated females admitted for 1-day detoxification, and 718
      randomly selected women (the controls). Irrespective of case definition, father's
      alcoholism, incomplete family of origin, conduct disorders in childhood and
      adolescence, and social surroundings marked by heavy drinking were supported as
      risk factors of alcoholism. A factor analysis of alcohol-related problems led to
      two dimensions (dependence, disruptiveness) and consequently to four types of
      female alcoholism with different patterns of risk factors.

PMID- 1399169
TI  - Young people, alcohol, and driving in two Australian states.
AB  - Road traffic accidents are the single largest cause of death in Australia among
      people aged 15-24. The proposition that a broadly based deterrence measure, such
      as random breath testing (RBT), would be sufficient to change the behavior of
      young drivers was tested in a comparison of young drivers in New South Wales
      (NSW), which has had RBT for 6 years, with young drivers in Western Australia
      (WA), where there was no RBT. The results demonstrated that NSW young drivers
      were less likely to drink and drive and more likely to believe their peers would
      disapprove of drink-driving than were their counterparts in WA. It was concluded
      that RBT had altered the drink-driving behavior and possibly the beliefs about
      drink-driving of young people in NSW.

PMID- 1399170
TI  - Has socialism failed? An analysis of health indicators under socialism.
AB  - This article analyzes the widely held assumption in academia and the mainstream
      press that capitalism has proven superior to socialism in responding to human
      needs. The author surveys the health conditions of the world's populations,
      continent by continent, and shows that, contrary to dominant ideology, socialism
      and socialist forces have been, for the most part, better able to improve health
      conditions than have capitalism and capitalist forces. In the underdeveloped
      world, socialist forces and regimes have, more frequently than not, improved
      health and social indicators better than capitalist forces and regimes, and in
      the developed world, countries with strong socialist forces have been better able
      to improve health conditions than those countries lacking or with weak socialist
      forces. The socialist experience has, of course, also included negative
      developments that have negated important components of the socialist project.
      Still, the evidence presented in this article shows that the historical
      experience of socialism has not been one of failure. To the contrary: it has
      been, for the most part, more successful than capitalism in improving the health
      conditions of the world's populations.

PMID- 1399171
TI  - Capitalism has not won.

PMID- 1399172
TI  - Myths and realities: Latin America's free markets.

PMID- 1399173
TI  - Why the United States does not have a national health program: the medical
      industry complex and its PAC contributions to congressional candidates, January
      1, 1981, through June 30, 1991. Common Cause.
AB  - The Common Cause study presents data on medical-industry PAC contributions to
      Members of Congress during the period January 1, 1981, through June 30, 1991.
      Included are listings of the top 25 congressional recipients, the top 25 Senate
      recipients, and the top 50 House recipients of contributions from medical
      industry PACs; medical-industry PAC contributions to members of the four key
      congressional committees and to the congressional leadership; top congressional
      recipients of contributions from medical professionals' PACs, including the
      American Medical Association, from health insurance PACs from pharmaceutical
      PACs, and from hospitals and care-provider PACs; and the top medical-industry
      PACs. State-by-state lists of medical-industry PAC contributions to Senators and
      to Representatives, including breakdowns of insurance, AMA, and pharmaceutical
      contributions, are given in the appendixes.

PMID- 1399174
TI  - From equal access to health care to equitable access to health: a review of
      Canadian provincial health commissions and reports.
AB  - Having achieved equality of access to health care, Canadian policymakers are
      setting new policy goals, within resource constraints, primarily to achieve
      equity of access to health. Across the country, provincial royal commissions have
      explored a number of policy options to achieve this goal. These options are
      reviewed and critically analyzed within the context of such challenges in health
      policy as insufficient access to high-technology care and the limits of medical
      care, and such external challenges as economic and demographic trends, federal
      provincial disputes, and ideological beliefs. Particular attention is given to
      the implications of a broader definition of health and the concept of regional
      health authorities. Based on the provincial reviews, the authors conclude that
      Canada wants to achieve equitable access to health. With the shift of health
      policy away from the formerly protected arena of medical care, achieving
      equitable access to health will require both an alteration of priorities and
      values and considerable political will. Canada will be forced to meet these new
      challenges to maintain current achievements and to make its system even more
      successful.

PMID- 1399175
TI  - Employer control and the work environment: a study of the Swedish Public Dental
      Service.
AB  - The Public Dental Service in Sweden has a system of surveillance and supervision
      based on time studies, piecework wages for dentists, and detailed time reporting.
      This control system and its development are described in this article. The focus
      is on the effects of the system on the staff. A representative group of Swedish
      dentists (n = 896) and dental nurses (n = 600) was asked to participate in a
      questionnaire study exploring the work environment in the Public Dental Service.
      The response rate was 87 percent. The dentists reported that they felt constantly
      supervised and evaluated. Their work tempo was related to surveillance,
      competition, and demands of the employer. There was no correlation between work
      tempo and piecework results. A high percentage of the staff mentioned weaknesses
      in the charging and piecework system that they thought could result in an
      undesirable influence on dentists' work. A majority would have preferred fixed
      salaries. The results are discussed in terms of gender, motivation,
      proletarianization, and management style.

PMID- 1399176
TI  - Leaving it up to the workers: sociological perspective on the management of
      health and safety in small workplaces.
AB  - Small workplaces present particular challenges for the promotion of occupational
      health and safety. However, little is known about the social organization of work
      in such settings and how it relates to matters of health and safety. The research
      on which this article is based relates patterns of occupational health behavior
      to the nature of social relationships within the workplace. From a qualitative
      analysis of interviews with 53 small business owners, the author describes the
      most common approach to managing workplace health and safety: leaving it up to
      the workers. This posture is explained in terms of the owners' perception of
      risk, particularly their understanding of workplace hazards, and their assessment
      of the social costs of ignoring or addressing such issues. Owners tended to
      discount or normalize health hazards, and to believe that management intervention
      in employee health behavior was paternalistic and inconsistent with prevailing
      patterns of labor relations and norms respecting individual autonomy. Many owners
      understood health and safety not as a bureaucratic function of management but as
      a personal moral enterprise in which they did not have legitimate authority. The
      conceptualization of the owners' responses in terms of "social rationality" has
      implications for addressing problems of health and safety in small workplaces.

PMID- 1399177
TI  - The industrial safety professionals: a comparative analysis from World War I
      until the 1980s.
AB  - The birth of industrial society produced demand for the services of professionals
      specialized in matters related to industrial safety. Three professions--safety
      engineering, industrial medicine, and ergonomics--are examined. These professions
      are observed to either submit to single sets of demands, to integrate
      contradictory demands, or to experience scission. Until the late 1960s their
      growth appears to have been relatively peaceful and uncontroversial. From this
      period onward, controversy breaks out over questions related to industrial
      safety, and professions and government administrations grow. Increasingly, the
      traditional approach of safety professionals is called into question, and they
      adopt new orientations. These changes are mapped through the examination of data
      drawn principally from the United States, France, Great Britain, and to a lesser
      extent Brazil. The traditional standards approach competes with cost-benefit
      analysis and with systemic safety for influence; in addition, an emergent
      approach that analyzes accident causes in terms of social relations of work is
      detected. From Bhopal to Chernobyl, new technologies subject civilian populations
      to risks of catastrophic accidents, and the action of safety professionals comes
      under the spotlight. The analysis constructed permits new understandings of the
      past and the future of these professions.

PMID- 1399179
TI  - The cancer war and its critics. The Washington Post.

PMID- 1399178
TI  - Environmental justice, regulation, and the local community.
AB  - This article examines the sociological significance of the concept of
      "environmental justice" for grassroots groups responding to toxic contamination
      in their local communities. Taking into account nationwide mobilization patterns
      in such communities, the author documents a precedent-setting episode in the city
      of Jacksonville, Arkansas, where citizen protests and support from national
      environmental groups led the Environmental Protection Agency to withdraw three
      Technical Assistance Grants inappropriately awarded to a group with links to a
      polluting industry, and subsequently to rewrite the rules for participation in
      such grants. As the first such challenge nationally, the Jacksonville scenario is
      an important "test case" and permits a theoretical and practical evaluation of
      the relationship between social groups, technology, and the governmental
      regulatory process. More particularly, it gives insight into the Technical
      Assistance Grants program, which was set up to enable citizens living close to
      contaminated sites to interpret and evaluate technical information relating to
      such sites, but which has been undercut by a weak EPA and cooptation efforts by
      industries. The article concludes with an exploration of the concept of community
      in relation to the new construction of environmental justice engaged in by
      grassroots groups fighting contamination locally and nationally.

PMID- 1399180
TI  - Nurses' professionalism in Canada: a labor process analysis.
AB  - This article draws on a body of research conducted by the author over the past
      ten years on the social organization of nursing work. It explores questions
      surrounding nurses' contemporary labor process control and its meaning for
      nurses' professionalization and proletarianization. Both are dynamic processes,
      changing as public administration of the Canadian health care system changes and
      as nurses are successful in winning more complete self-regulation. Nurses are
      currently being articulated more and more securely to dominant ideas of public
      sector management through textually mediated technologies. Nurses find new
      upwardly mobile careers and challenging, responsible, and more respected work.
      However, as the generation of objective information for professional
      accountability, cost-accounting, and managerial decision-making becomes unified
      in computerized patient information systems, producing and using such information
      becomes a central and determining core of everyday nursing work. It organizes
      nurses into a "managed" practice of patient care, contradictory for them in many
      ways. Outstanding among these contradictions is a new professionalized standpoint
      of cost-efficiency that subordinates nurses' traditional interests and grounding
      of their work in the standpoint of care.

PMID- 1399181
TI  - From a policy of inequality to a proposal of equity: political processes and
      health care in the municipality of Sao Paulo.
AB  - A tentative analysis is made of the recent Sao Paulo experience in health care
      management, in which the chief guideline has been to create institutional space
      for grass-roots and health worker participation within the State apparatus. The
      analysis takes Brazil's recent health policies and the so-called Sanitary Reform
      movement as reference points. The issue is approached from the angle of democracy
      and democracy's possibilities in the context of a society characterized by
      tremendous social inequalities, and in the context of the current international
      and national neoliberal offensive.

PMID- 1399182
TI  - Comments on the thoughts of Gail Wilensky (advisor to President Bush on health
      and welfare reform) on the Canadian health system.

PMID- 1399183
TI  - Sources of disagreement among clinicians' assessments of dangerousness in a
      psychiatric emergency room.

PMID- 1399184
TI  - A review of arrests among psychiatric patients.

PMID- 1399185
TI  - Interactions between civil commitment and protective placement: an empirical
      assessment.

PMID- 1399186
TI  - Pathological firesetting in adults.

PMID- 1399187
TI  - Neuropsychology, personality, and substance abuse in the head injury case:
      clinical and forensic issues.

PMID- 1399189
TI  - On narcissism and veiled innocence: prolegomena to a critique of criminal law.

PMID- 1399188
TI  - The need to commute the death sentence: competency for execution and ethical
      dilemmas for mental health professionals.

PMID- 1399190
TI  - Nail cosmetics.

PMID- 1399191
TI  - Esophageal manifestations in autoimmune bullous diseases.

PMID- 1399192
TI  - Ethics of organ transplantation.

PMID- 1399193
TI  - Drug delay and the FDA.

PMID- 1399194
TI  - Tsutsugamushi disease (scrub typhus).
AB  - Two patients with Tsutsugamushi disease (fever) were successfully treated with
      tetracycline derivatives after typical eschars were found, although one of the
      patients was initially misdiagnosed as having a drug reaction eruption. Prompt
      diagnosis and treatment are important because this disease can be associated with
      considerable morbidity and simple effective treatment is easily available.

PMID- 1399195
TI  - Granuloma inguinale: three cases diagnosed in Toronto, Canada.
AB  - Granuloma inguinale (GI) is a sexually transmitted disease seldom seen in the
      United States and Canada. We are reporting three cases recently seen in Toronto,
      Ontario, two in immigrants, and one in a native born Canadian who had an intimate
      relationship with a foreign visitor. The basic features of the disease are
      discussed.

PMID- 1399196
TI  - Microbiology of secondarily infected diaper dermatitis.
AB  - Specimens obtained from 67 infants with secondarily infected diaper dermatitis
      were cultured for aerobic and anaerobic bacteria. Bacteria growth was obtained in
      58. Aerobic facultative bacteria or Candida sp. only were present in 28 patients
      (48%), anaerobic bacteria only in 11 (19%), and mixed anaerobic with aerobic,
      facultative, or yeast flora was present in 19 (33%). Ninety-one bacterial or
      fungal isolates were recovered (1.6 per specimen), 54 (0.9 per specimen) aerobic
      or facultative bacteria, 8 (0.1 per specimen) Candida sp., and 31 (0.6 per
      specimen) strict anaerobes. The predominant aerobic and facultative bacteria were
      Staphylococcus aureus (23 isolates), Streptococcus sp. (16), and Escherichia coli
      (6). The predominant anaerobes included Bacteroides sp. (12, including 9
      Bacteroides fragilis group) and Peptostreptococcus sp. (11). Single bacterial
      isolates were recovered in 32 (55%) patients, 18 of which were S. aureus. Twenty
      five beta-lactamase-producing bacteria were detected in 22 (51%) of the 43 tested
      patients. These included 16 S. aureus and 6 B. fragilis group. These data
      highlight the importance of anaerobic bacteria in the polymicrobial nature of
      secondarily infected diaper dermatitis.

PMID- 1399198
TI  - Trichorhinophalangeal syndrome.

PMID- 1399197
TI  - Pilomatricoma: a retrospective study.
AB  - A study of 53 Pakistani patients with pilomatricoma diagnosed at AFIP during 1985
      1989 is presented. It constituted 37.2% of all benign adnexal tumors, during the
      same period. 56.2% of patients were more than 30 years of age. Differences in
      site, sex, and age distribution from Western reports were observed. Unusual
      clinical presentations were also noted. This study outlines the clinicopathologic
      features of pilomatricoma in Pakistan.

PMID- 1399199
TI  - Ascher's syndrome: an unusual case with entropion.

PMID- 1399200
TI  - Intravascular papillary endothelial hyperplasia: a reorganizing thrombus.

PMID- 1399201
TI  - Leukodermic macules in keratosis follicularis (Darier's disease).

PMID- 1399202
TI  - Granulomatous rosacea associated with Demodex folliculorum.

PMID- 1399203
TI  - Terbinafine: efficacy and safety in the treatment of dermatophytosis.
AB  - A double-blind study with terbinafine was performed in 39 patients with
      dermatophyte infection, between 1987 and 1989, to compare the safety and efficacy
      of two dosage schedules of 125 mg twice daily versus 250 mg once daily. Mycologic
      assessments were negative by microscopic examination and Sabouraud's culture in
      59% and 100% of patients in the first and the fourth weeks of treatment,
      respectively. There was no statistically significant difference between the two
      groups of patients receiving 125 mg b.i.d. and 250 mg q.d. with respect to the
      safety and efficacy of the treatment; however, the differences between the sums
      of clinical scores before and after the treatment were statistically significant.
      There were no adverse effects, and the drug was well tolerated.

PMID- 1399204
TI  - Enalapril: a powerful in vitro non-thiol acantholytic agent.
AB  - Drugs containing sulfhydryl groups (thiol drugs) (e.g., penicillamine, captopril,
      thiopronine) can induce pemphigus in vivo and provoke acantholysis in vitro.
      Enalapril, like captopril, is an angiotensin-converting enzyme (ACE) inhibitor
      largely used as an antihypertensive drug; it has recently been reported to induce
      pemphigus, though it is not a thiol drug. In this study we investigated the
      possible in vitro acantholytic effect of enalapril on normal human skin from
      donors. The drug induced severe acantholytic changes of keratinocytes and
      complete suprabasal splitting at one tenth the concentration required by thiol
      drugs in similar experiments, even after a shorter period of culture. All skin
      samples from different donors was highly susceptible to the acantholytic effect
      of enalapril. In our experience, enalapril is the most powerful acantholytic drug
      in vitro.

PMID- 1399205
TI  - Saperconazole in the treatment of systemic and subcutaneous mycoses.
AB  - In a 2-year period, 30 patients with culture-proven mycoses (chromoblastomycosis,
      sporotrichosis, and paracoccidioidomycosis) were treated with the new orally
      administered triazole, saperconazole (SPZ) (R66905). The daily dose varied from
      100 to 200 mg. All patients responded to treatment; the mean time required to
      heal the lesions and convert the cultures to negative was 3.5 months for
      sporotrichosis, 4.6 for paracoccidioidomycosis, and 9.0 for chromoblastomycosis.
      Evaluation by a scoring system indicated that 36.6% of the patients achieved
      complete resolution of the pretherapy abnormalities, while the remaining (63.3%)
      experienced major improvement. No collateral effects were reported; there were no
      bone-marrow or liver toxicities. SPZ is an effective drug for the treatment of
      the above-mentioned mycoses and appears to be suitable for the control of
      chromoblastomycosis.

PMID- 1399206
TI  - Recessive dystrophic epidermolysis bullosa treated with phenytoin.
AB  - Three patients with severe recessive dystrophic epidermolysis bullosa were
      treated with oral phenytoin and palliative and supportive measures for variable
      periods. Their progress was compared with that of three milder cases managed only
      with palliative and supportive measures. The phenytoin-treated group showed
      marked decrease in blister count, increase in trauma tolerance, a rise in
      hemoglobin level, and considerable weight gain. The results support earlier
      reports that collagenase inhibitors are useful in controlling blister formation
      in recessive dystrophic epidermolysis bullosa.

PMID- 1399208
TI  - Warfarin in the treatment of psoriasis.

PMID- 1399207
TI  - Professor Sir Thomas McCall Anderson (1836-1908).

PMID- 1399209
TI  - Buruli ulcer and HIV infection.

PMID- 1399210
TI  - Pityriasis rotunda and G6PD deficiency.

PMID- 1399211
TI  - Granuloma annulare arising after herpes zoster.

PMID- 1399213
TI  - Non-itchy lichen amyloidosus.

PMID- 1399212
TI  - Perifolliculitis capitis abscedens et suffodiens.

PMID- 1399214
TI  - Pentoxifylline treatment for beta-thalassemia intermedia leg ulcer.

PMID- 1399215
TI  - Maternal alcohol consumption and child development.
AB  - Studies of development and behaviour from shortly after birth up to the age of 7
      years are reviewed. Maternal alcohol consumption above 150-200 g/week is related
      to behaviour in many studies, but below this level there is little
      epidemiological evidence of association. There is no evidence that the levels of
      consumption associated with adverse behaviour are lower than those associated
      with adverse pregnancy outcome.

PMID- 1399216
TI  - Animal models of prenatal alcohol exposure.
AB  - Since the first reports of fetal alcohol syndrome (FAS), thousands of studies
      have examined the effects of antenatal alcohol exposure in humans and in animal
      models. Research with animal models has led to discoveries which would be
      difficult if not impossible in human subjects. Most importantly, these models
      have resulted in valuable insights into the actions of alcohol on various parts
      of the developing embryo and have helped researchers come closer to identifying
      the mechanisms of its teratogenic action. Both the direct and indirect biological
      effects of alcohol exposure in utero appear to work in conjunction with other
      concurrent and predisposing factors such as genotype, nutritional status, pattern
      of exposure and use of other drugs such as nicotine and cocaine. At present
      animal research indicates a multifactorial mechanism of the teratogenicity of
      alcohol resulting from nutrient deficiencies, fetal hypoxia and alterations in
      enzyme activities and cell function important in cell division and membrane
      integrity. This review examines how animal models are used to clarify issues
      associated with alcohol-related birth defects and to shed light on the underlying
      mechanisms.

PMID- 1399217
TI  - The impact of alcohol misclassification on the relationship between alcohol and
      pregnancy outcome.
AB  - Underreporting, more than overreporting, is a problem in studies of the effects
      of alcohol consumption using self-reported data. Numerical examples illustrate
      that in studies of the effect of alcohol, nondifferential misclassification of
      alcohol consumption due to underreporting may lead to a bias away from the null
      value. It may also cause a true threshold level for alcohol to appear as a dose
      response relationship. It is shown that the effect of misclassification on effect
      estimates will depend on the true frequency of abstainers in the studied
      population.

PMID- 1399218
TI  - EUROMAC. A European concerted action: maternal alcohol consumption and its
      relation to the outcome of pregnancy and child development at 18 months. Methods.

PMID- 1399219
TI  - EUROMAC. A European concerted action: maternal alcohol consumption and its
      relation to the outcome of pregnancy and child development at 18 months. Methods-
      comparison between centres.

PMID- 1399220
TI  - EUROMAC. A European concerted action: maternal alcohol consumption and its
      relation to the outcome of pregnancy and child development at 18 months. Results-
      strategy of analysis and analysis of pregnancy outcome.
AB  - Analyses were made of the relation between maternal alcohol consumption before
      and in early pregnancy and five infant outcome variables: birthweight, crown-heel
      length, occipitofrontal circumference and the Apgar scores at 1 and 5 minutes.
      The data were analysed for all centres combined and separately. From tabulation
      of the mean values of the outcome variables by alcohol consumption, it appeared
      that a poorer outcome was related to consumption of 120 g/week absolute alcohol
      or more. Multiple regression analysis was used to allow for possible confounding
      by the child's gestational age at birth and sex, the mother's age, parity and
      smoking habit, and survey centre. Two threshold models were applied to the
      combined data, taking the confounders into account. The offset threshold model
      (assuming no effect of alcohol up to a threshold value, and then a constant
      multiplicative effect at higher levels) suggested a negative effect on
      birthweight at about 60 g/week absolute alcohol, but with a wide 85% confidence
      interval of 5-130 g/week. A step function threshold model, which assumes a
      constant effect above the threshold value, behaved erratically. Similar analyses
      for crown-heel length and occipitofrontal circumference provided only a very poor
      fit to the data. Data on reported congenital anomalies are presented by survey
      centre and maternal alcohol consumption, but due to the unstandardized method of
      collection they were not analysed further.

PMID- 1399221
TI  - EUROMAC. A European concerted action: maternal alcohol consumption and its
      relation to the outcome of pregnancy and child development at 18 months. Results-
      child development at age 18 months.
AB  - Children seen in the first part of the study in Berlin, Dundee and Odense were
      followed up at age 18 months and tested using the Bayley Scales of Infant
      Development. Five scores were recorded: the Mental Development Index (MDI), the
      Psychomotor Development Index (PDI) and scores for responsiveness, attention span
      and activity. The data were analysed for the centres combined and separately,
      allowing for confounding variables as in the previous chapter. In none of the
      comparisons was the mean score found to be significantly less in the children of
      drinkers than in those of abstainers. In many of the comparisons the children of
      abstainers had the lowest mean scores. In a number of comparisons in Berlin and
      Dundee, the MDI or PDI was found to be significantly higher in the children of
      women who had drunk at the upper end of the consumption distribution.

PMID- 1399222
TI  - EUROMAC. A European concerted action: maternal alcohol consumption and its
      relation to the outcome of pregnancy and child development at 18 months. Relation
      of findings to other studies.

PMID- 1399223
TI  - Alcohol and the fetus.
AB  - The teratogenic effects of alcohol have been recognized in the fetal alcohol
      syndrome. The syndrome is associated with very high levels of maternal
      consumption. Studies of the relation between much lower levels of consumption and
      pregnancy outcome seem to indicate consistently lower birthweight among children
      born to mothers drinking more than 140 g absolute alcohol per week, or about two
      drinks a day.

PMID- 1399224
TI  - EUROMAC. A European concerted action: maternal alcohol consumption and its
      relation to the outcome of pregnancy and child development at 18 months.
      Recommendations.

PMID- 1399225
TI  - Endometrial stromal sarcomas of the uterus with extensive endometrioid glandular
      differentiation: a report of three cases that caused problems in differential
      diagnosis.
AB  - Three cases of endometrial stromal sarcoma (ESS) with prominent glandular
      differentiation within the primary or recurrent tumors are described. Each case
      posed a problem in diagnosis and classification. The patients, who ranged in age
      from 41 to 47 years, presented with abnormal uterine bleeding, a pelvic mass, or
      a combination thereof. All the patients underwent hysterectomy with or without
      bilateral salpingo-oophorectomy. There was no evidence of extrauterine spread of
      tumor in any case. Polypoid tumors involved the endometrium in two cases, and in
      one of them, tumor deeply invaded the myometrium. The tumor in the third case was
      an infiltrative mass that was confined to the myometrium and its vessels. On
      microscopic examination, the tumors were low-grade ESSs that contained large
      numbers of endometrioid glands, which were benign appearing in two cases, and in
      the third varied from atypical to carcinomatous. In one of the cases in the first
      group, the glandular component was present only in recurrent tumor excised 10
      years after hysterectomy; prominent foci of sex-cord-like differentiation were
      also present in the recurrent tumor. This patient was clinically free of tumor 27
      months later; follow-up in the other two patients was uneventful. ESSs with
      prominent numbers of benign-appearing glands should be distinguished from
      adenomyosis, endometriosis, ESSs arising in adenomyosis or endometriosis, ESSs
      with sex-cord-like differentiation, and mullerian adenosarcomas. ESSs with
      carcinomatous glands should be distinguished from endometrial adenocarcinomas and
      malignant mullerian mixed tumors (carcinosarcomas). Extrauterine lesions that
      have been designated "aggressive endometriosis" may be examples of extrauterine
      ESS with prominent glandular differentiation.

PMID- 1399226
TI  - Nd:YAG laser endometrial ablation: histological aspects of uterine healing.
AB  - Laser ablation of the endometrium performed under hysteroscopic control is a
      novel procedure for the conservative management of menorrhagia in cases of
      dysfunctional uterine bleeding. The effect this has on the uterine cavity and the
      mechanism of reepithelialisation and endometrial regeneration have been examined
      by means of histological examination of endometrial biopsies and four
      hysterectomy specimens obtained for various indications at varying time intervals
      after laser endometrial ablation. During the first 3 months, fragments of
      necrotic and granulation tissue are found surrounded by a limited polymorph
      response. By 3 months, the uterine cavity appears to be completely
      reepithelialised. After 6 months, areas of normal-appearing endometrium may
      persist, but in other areas there is an attenuated cuboidal surface epithelium
      closely applied, to the underlying myometrium. Stromal fibrosis reminiscent of
      Asherman syndrome is also apparent.

PMID- 1399227
TI  - Hereditary ovarian cancer: a clinicopathological study.
AB  - Hereditary ovarian cancer (HOC) is rare and little recognized. Over the years, we
      have identified 37 HOC patients from HOC syndrome kindreds with documented
      cancers of ovary, breast, colon, or endometrium in two or more first-degree
      relatives. The age and clinical stage at diagnosis and overall 5-year survival of
      HOC patients were compared with those of ovarian cancers in the unselected
      patients. The gross and microscopic features of the tumors are compared with a
      set of 34 consecutively chosen ovarian cancer cases with documented negative
      family histories. The mean age of HOC patients at diagnosis was significantly
      lower (50.2 years) than that of the unselected control population (59 years) (p
      less than 0.001). Detailed pedigree analysis breaks down the HOC group into (a)
      site-specific ovarian cancer, 5 cases, 56.4 years mean age; (b) breast-ovarian
      cancer syndrome, 28 cases, 50.46 years mean age; and (c) Lynch syndrome II
      (colon/endometrial cancer), 4 cases, mean age 41 years. The age differences were
      statistically significant (p = 0.050). The most prevalent International
      Federation of Gynecology and Obstetrics clinical stage at diagnosis of HOC (stage
      III) was the same as for the control group. Histologically, all (100%) HOC tumors
      were surface epithelial cancers with predominance of serous papillary type
      moderate to high grade (89 versus 71% in control, p = 0.07). No other pathologic
      features appeared to be significant. In conclusion, HOC is a serous papillary
      tumor and characterized by early age of onset and excess of breast/ovary/colon
      endometrial cancers in first-degree relatives of patients with specific HOC
      syndromes.

PMID- 1399228
TI  - Flow cytometric DNA analysis of ovarian Brenner tumors and transitional cell
      carcinomas.
AB  - Flow cytometry has been previously used as a method of obtaining prognostic
      information about ovarian carcinomas using ploidy, DNA index, and S-phase
      fraction. DNA content has also been assessed in ovarian tumors of low malignant
      potential. Brenner tumor variants such as metaplastic, proliferating, and low
      malignant potential, recently designated as intermediate Brenner tumors, and
      malignant Brenner tumors are unusual tumors that present classification problems.
      Their histological appearance may not accurately reflect biological activity. We
      used flow cytometry to analyze paraffin-embedded tissue for DNA content and S
      phase in 34 Brenner tumors, three ovarian transitional cell (urothelial)
      carcinomas (TCCs), and nine normal control ovaries. We correlated histological
      and clinical features with DNA analysis. Twenty-five Brenner tumors and three
      ovarian TCCs were acceptable for histogram analysis (coefficient of variation
      less than 7.0). Thirteen typical, three metaplastic (extensive mucinous or
      glandular metaplasia), and two proliferating (papillary formation with increased
      cellularity) Brenner tumors were diploid. One proliferating tumor was tetraploid.
      The single Brenner tumor of low malignant potential was diploid but had an
      increased S-phase. Four of five malignant Brenner tumors were aneuploid, and one
      was diploid. All the TCCs were aneuploid. S-phase was elevated in intermediate
      and malignant Brenner tumors and TCC. Limited numbers of cases available preclude
      prognostic prediction based on ploidy in malignant Brenner tumors or primary
      ovarian TCCs. DNA ploidy and S-phase reflect the intermediate status of
      metaplastic, proliferating, and low malignant potential Brenner tumors.

PMID- 1399229
TI  - Distribution of tumor-associated glycoprotein-72 (TAG-72) expression throughout
      the normal female reproductive tract.
AB  - Compared with the degree of investigation of stage-specific expression of tumor
      associated glycoprotein-72 (TAG-72) in fundal endometrium, other regions of the
      female reproductive tract have not received comparable attention. Regional, cell
      type-specific, and temporal differences in estrogen receptor and progesterone
      receptor distribution and concentration among these tissues should make such
      examination beneficial to our understanding of hormonal regulation of TAG-72
      expression. The pattern of monoclonal antibody (MAb) B72.3 recognition in the
      cervix, uterus, oviduct, and ovary was examined by immunohistochemistry during
      both the proliferative and secretory intervals of the normal menstrual cycle.
      Intense immunoreactivity in fundal endometrium was limited to the secretory
      menstrual interval. Conversely, TAG-72 expression was generally weaker,
      sporadically distributed, and not stage specific in the lower uterine segment,
      endocervix, and cervix; no expression was detected in the oviduct or ovary. The
      disparity in both temporal and spatial distribution of TAG-72 expression
      throughout the female reproductive tract does not appear to be directly
      associated with the well-described changes in circulating estradiol or
      progesterone or the receptors for these steroids. Results suggest that regulation
      of TAG-72 expression may involve local paracrine/autocrine mechanisms, which in
      turn may be subject to hormonal influence.

PMID- 1399230
TI  - Epithelioid hemangioendothelioma of the clitoris: a case report with
      immunohistochemical and ultrastructural findings.
AB  - A 30-year-old woman was referred for evaluation of a small nodule of the
      clitoris. This was subsequently diagnosed as epithelioid hemangioendothelioma.
      This rare vascular tumor of intermediate malignancy has not been previously
      described in the vulva. The patient underwent a modified radical vulvectomy and
      bilateral inguinal lymph node dissection, and subsequently received photon
      therapy. She is alive with no evidence of disease 27 months after diagnosis.

PMID- 1399231
TI  - Polypoid cystic adenomyosis of the uterus: report of a case.
AB  - A case of focal adenomyosis of the uterus with unusual gross features is
      presented. The patient, a 43-year-old woman, had experienced abnormal vaginal
      bleeding for 8 years. Hysteroscopy revealed a polypoid mass compatible with a
      submucosal leiomyoma, and a hysterectomy was performed. The uterus showed a 7 x 5
      x 3-cm firm polypoid mass attached to the anterior wall that occupied most of the
      uterine cavity and protruded through the cervical os. It contained a large,
      central, cystic cavity filled with bloody fluid that communicated with the
      endometrial cavity through a fistula-like tract. Both the surface of the mass and
      the inside of the cystic cavity were covered by endometrial mucosa, and there
      were endometrial islands in the intervening wall. The differential diagnosis of
      this unique form of adenomyosis included polypoid submucosal leiomyoma with
      invagination of endometrium, endometrial polyp, submucosal leiomyoma with
      invagination of endometrium, endometrial polyp, and uterine diverticulum.

PMID- 1399232
TI  - Expression of epidermal growth factor receptor in normal ovary and in ovarian
      tumors.
AB  - Increased expression of epidermal growth factor (EGF) receptor has been recorded
      in many types of human tumors and has been associated with reduced survival in
      ovarian carcinoma. The purpose of this study was to examine the
      immunocytochemical distribution of the EGF receptor in normal ovaries (n = 30)
      and in ovarian tumors (n = 126). Staining was observed in two normal ovaries, in
      the granulosa cells of a developing follicle, and in surface epithelium. Forty
      seven of 103 malignant common epithelial tumors were immunopositive. Staining was
      usually focal, always confined to the neoplastic epithelium, and showed a
      cytoplasmic distribution. There was a slight trend for increased EGF receptor
      expression in more advanced common epithelial malignancies, but this was not
      statistically significant. No correlation between immunoreactivity and
      histological subtype or grade of tumor was seen. A few other tumors were also
      examined: one each of Brenner tumor, mature teratoma, mature teratoma with
      squamous carcinoma, borderline serous tumor and fibroma; all were immunopositive.

PMID- 1399233
TI  - Clomiphene's effect on endometrium in infertility.
AB  - Secretory-phase endometrium from patients receiving clomiphene has an
      identifiable, distinctive character. We reviewed 710 endometrial biopsies from
      566 infertility patients, including 108 from 79 patients receiving clomiphene.
      Endometrial glands in biopsies from clomiphene-treated patients were straight,
      narrow, and less tortuous than normal. Gland-to-stroma ratio was decreased. In
      the early secretory phase, glands had crisp subnuclear vacuoles and distinct
      glandular lumenal borders. Secretions were scant throughout the secretory phase,
      with few apical snouts. Lumenal secretions appeared inspissated and hyaline-like.
      Late secretory epithelium was generally low cuboidal and rarely showed
      hypersecretory change. Stromal predecidualization in the late phase showed
      progression, but in some cases decidual cells were smaller than usual. All of
      these features are consistent with a hypoestrogenic effect.

PMID- 1399234
TI  - Diffuse adenomatoid tumor of the uterus with a serosal papillary cystic
      component.
AB  - A 39-year-old woman undergoing immunosuppressive therapy following kidney
      transplantation for systemic lupus erythematosus presented with a uterine
      adenomatoid tumor that diffusely infiltrated the entire myometrium and contained
      a serosal papillary cystic component that resembled a cystic mesothelioma. This
      is the first reported case of an adenomatoid tumor showing both of these
      features. Although adenomatoid tumors are considered benign, the patient may be
      at risk for recurrence of the papillary cystic component (which is known to recur
      in 50% of cases) if this tumor reflects an inability to limit neoplastic
      processes.

PMID- 1399235
TI  - Endometrial stromal nodule with smooth and skeletal muscle components simulating
      stromal sarcoma.
AB  - A stromal nodule was found in a hysterectomy specimen from a 29-year-old woman
      with a history of menometrorrhagia. Endometrial curettings had revealed stromal
      cells admixed with well-defined bundles of smooth muscle cells, a finding that
      had led to the erroneous diagnosis of stromal sarcoma invading the myometrium.
      Ultrastructural and immunohistochemical studies demonstrated several components:
      stromal cells, smooth muscle cells, sex-cord-like structures, and a hitherto
      undescribed component of skeletal muscle cells.

PMID- 1399236
TI  - Cytologic features of malignant ovarian monodermal teratoma with an ependymal
      component in peritoneal washings.
AB  - A case of malignant neuroectodermal tumor of the ovary (monodermal teratoma) with
      a predominant ependymal component in the peritoneal washings of a 27-year-old
      woman obtained on second-look laparotomy is presented and discussed. The smear
      and cell block preparations showed sheets and clusters of cells containing oval
      nuclei with finely granular chromatin and small nucleoli. The cell
      nuclear/cytoplasmic ratio was within normal limits, and minimal cytologic atypia
      was observed. The clusters were rimmed by columnar-oriented cells lined by cilia.
      This is the first reported case of this rare ovarian neoplasm present on fluid
      cytology. Its bland cytologic appearance could be confused with endosalpingiosis.

PMID- 1399237
TI  - The Bancroft-Mackerras Medal of the Australian Society for Parasitology. 1991
      Award to R. C. A. Thompson.

PMID- 1399239
TI  - The partial characterization of proteases present in the excretory/secretory
      products and exsheathing fluid of the infective (L3) larva of Necator americanus.
AB  - Following the observation that live third-stage larvae (L3) could digest gelatin
      in vitro, gelatinolytic protease activity has been demonstrated at pH 8.5, in
      both exsheathing fluid (EF) and excretory/secretory (ES) products of infective L3
      of Necator americanus. EF resolved as a single band of proteolytic activity, with
      a mol. wt of 116 kDa, while L3 ES products exhibited multiple bands of
      proteolysis, at 219, 200, 195, 166, 137, 92, 72 and 62 kDa; weak bands were
      detectable at 92 and 72 kDa. The EF protease was characterized as cysteine,
      whereas ES apparently possessed one serine (195 kDa) and seven (219, 200, 166,
      137, 92, 72 and 62 kDa) cysteine protease bands and a combination of metallo- and
      cysteine proteases of approximately the same mol. wts (62, 137 and 219 kDa).
      Though EF was not able to cleave immunoglobulins, ES was shown to cleave IgG, IgA
      and IgM, but not IgD or IgE. The activity appeared to be directed toward the Fc
      portion of the molecule, and was inhibited by PMSF, which is indicative of serine
      protease activity. The significance of the presence of such apparently diverse
      proteases in larval products is discussed.

PMID- 1399238
TI  - Parasitic zoonoses--problems created by people, not animals.

PMID- 1399241
TI  - Allozyme variation between laboratory reared and wild populations of Teladorsagia
      circumcincta.
AB  - The technique of allozyme electrophoresis was applied to two laboratory strains
      (isolated from the center or south-east of France) and wild populations of
      Teladorsagia circumcincta from the center of France. Five systems out of 13 (GPI,
      MPI, MDH, LDH, PGM) could be interpreted. By means of a multivariate analysis, it
      was shown that the laboratory strains were very similar with each other and
      genetically different from the wild populations. A deficiency of heterozygotes
      was recorded for each enzyme locus (except for MDH) in all populations studied.

PMID- 1399240
TI  - Skin penetration by ensheathed third-stage infective larvae of Necator
      americanus, and the host's immune response to larval antigens.
AB  - In vitro experiments were conducted to assess skin penetration by ensheathed
      third-stage infective larvae (L3) of Necator americanus. The fact that only a
      small proportion of larval sheaths was recoverable from the outer skin surface
      suggested that some larvae penetrate mouse skin without undergoing exsheathment.
      Penetration by ensheathed larvae was confirmed visually using a novel fluorescein
      isothiocyanate (FITC)-labelling technique in which viable ensheathed larvae were
      fluoresceinated, applied onto intact mouse skin, and their progress monitored in
      frozen skin sections. This direct observation that the L2-derived sheath can
      present antigens to the host's immune system was also monitored by immunoassay to
      provide confirmatory information regarding skin penetration by ensheathed larvae.
      Sera from humans infected with Necator americanus were shown to react in ELISA
      against antigens stripped by detergent (cetyltrimethylammonium bromide) from the
      sheath surface, and with antigens contained in L3-exsheathing fluid. These data
      suggest that the host's immune response, as a result of antigenic stimulation by
      the cast sheath and exsheathing fluid, could in fact be diverted away from the
      potentially vulnerable L3 stage.

PMID- 1399242
TI  - Incorporation of radiolabelled amino acids by adult Schistosoma japonicum:
      further characterization of a putative eggshell precursor protein.
AB  - The synthesis patterns of female-specific proteins of Schistosoma japonicum were
      further investigated with particular reference to the 34 kDa putative eggshell
      precursor protein. Adult male and female worms of S. japonicum were metabolically
      labelled with 14C-tyrosine, 14C-glycine and 35S-methionine in vitro. The rates of
      amino acid incorporation for female worms were significantly higher than for
      males in all radiolabelling experiments. Labelled proteins were resolved by two
      dimensional gel electrophoresis and visualized by fluorography. By using 14C
      tyrosine and 14C-glycine, the 34 kDa female protein band resolved into three
      major spots with pI 6.0, 5.8 and 5.6. On the other hand, labelling studies using
      35S-methionine failed to reveal synthesis of any corresponding spots at Mr 34
      kDa. These results, together with the observations that eggshell hydrolysates are
      very rich in glycine but poor in methionine, suggested that the 34 kDa putative
      eggshell precursor protein of S. japonicum consists of at least three isoelectric
      forms. In addition, we have demonstrated several other female-specific
      polypeptides synthesized by this worm.

PMID- 1399243
TI  - Patent infections of Ascaris suum in pigs: effect of previous exposure to
      multiple, high doses of eggs and various treatment regimes.
AB  - Fifty-four crossbred, 4-week-old pigs divided into nine equal groups were used to
      test whether multiple inoculations with high numbers of A. suum eggs with or
      without anthelmintic would result in patent infections. All pigs exposed to
      multiple prechallenge inoculations of 500, 1000, 2000, 5000, 10,000 and 20,000
      and challenged orally 2 weeks later with 10,000 eggs harboured adult worms. When
      prechallenge infections were removed by pyrantel tartrate treatment the animals
      were more susceptible to challenge than controls not previously exposed to
      infections. The same drug used from 2 days before until 10 days after the last
      prechallenge infection eliminated that effect. Pigs subjected to the same
      multiple egg dosing regimen but given feed containing fenbendazole immediately
      before, during and for 10 days after multiple dosing developed significantly more
      adult intestinal worms after challenge than any other group. These worms were,
      however, significantly shorter than those that developed in any group of pigs.
      Adult worms from all these groups produced eggs that after embryonation were
      infective to mice.

PMID- 1399244
TI  - Identification of immunodominant Trypanosoma musculi antigens recognized by
      monoclonal antibody and curative immunoglobulin G2a antibody.
AB  - Trypanosoma musculi obtained from normal or irradiated (900 rad) hosts or from in
      vitro cultures were lysed and analysed by sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis (SDS-PAGE). Similar protein banding patterns with a molecular
      weight (mol. wt) range from 34 to 68 kDa were observed between the two
      bloodstream forms. In comparison, lysates of cultured parasites showed a unique
      banding pattern of antigens within the same mol. wt range. Western blot of
      bloodstream form lysates, probed with immune plasma (IP), revealed a wide range
      of parasite proteins. However, when probed with the IgG2a-enriched fraction of
      IP, a major band of approximately 66 kDa was detected on the blot. Several bands
      of higher mol. wt were also observed. When anti-T. musculi monoclonal antibodies
      were used to probe the blot, the 66 kDa protein was again recognized. Using
      indirect fluorescence, live bloodstream form parasites were analysed by flow
      cytometry and the p66 protein was determined to be a surface molecule. Finally,
      lysates of 35S-methionine-labelled trypanosomes were immunoprecipitated with
      Sepharose linked anti-T. musculi monoclonal antibodies and the eluted ligand
      analysed by SDS-PAGE and autoradiographed. The 66 kDa band was identified,
      therefore confirming that this protein was of parasite origin.

PMID- 1399245
TI  - Ultrastructural observations on the marginal hooklets of the monogenean gill
      parasite Cichlidogyrus halli typicus.
AB  - The marginal hooklets of adult Cichlidogyrus halli typicus have the same
      morphology, each being composed of a handle, a curved blade with a tapering guard
      and an accessory domus. In addition, all the hooklets except those of pair II
      have a long extension attached to the proximal end of the handle. Ultrastructural
      observations reveal that the handle consists of three distinct layers whereas
      both the guard and the proximal region of the blade lack the outer electron-dense
      layer. The dense core is absent from the rest of the blade. The extension has a
      fibrous structure and an affinity for eosin, unlike the rest of the hooklet.
      There is a conspicuous cavity associated with each hooklet. The cavity is partly
      lined with a syncytial cytoplasmic epithelium containing secretory bodies. The
      lining is completed by the cytoplasmic covering of the handle; this covering may
      be the surviving oncoblast cell and has knob-like structures of unknown function
      projecting into the cavity. The domus has the appearance of two filaments with
      the light microscope but with the electron microscope these are seen to be the
      thickened edges of a single gutter-shaped sclerite.

PMID- 1399246
TI  - Vaccination of cattle with dextran sulphate-binding Babesia bigemina antigens.
AB  - Dextran sulphate-bound Babesia bigemina antigens were used in a preliminary
      vaccination study and were shown to elicit a protective immune response in
      cattle. A dextran sulphate-binding fraction of B. bigemina was further
      subfractionated on a Phenyl Sepharose column to give two fractions--one that
      strongly bound to the column (bound fraction) and one that did not (unbound
      fraction). Two groups of cattle were each vaccinated with either the bound or the
      unbound fraction. These two groups of animals along with a control group were
      then challenged with B. bigemina-infected erythrocytes. Both groups of vaccinated
      animals showed considerably lower mean daily parasitaemias as compared to the
      control group.

PMID- 1399247
TI  - Demonstration of the humoral immune response of horses to Babesia caballi by
      western blotting.
AB  - Babesia caballi-infected or normal equine erythrocytes were solubilized in sodium
      dodecyl sulfate (SDS) buffer and analyzed by SDS-polyacrylamide gel
      electrophoresis (SDS-PAGE) and Western blotting. Antigens were allowed to react
      with sera from horses experimentally or field-infected with B. caballi and with
      sera from non-infected horses. Major babesial antigens recognized by immune sera
      had apparent mol. wts of 141, 112, 70, 50, 48, 34, and 30 kDa. The polypeptides
      at 50 and 48 kDa were recognized earliest and throughout infection, but also
      weakly by 3/100 equine sera tested negative and 1/33 sera tested false positive
      by the complement fixation test (CFT) and immunofluorescence antibody test
      (IFAT). Thus, further characterization and purification of B. caballi antigens
      are required to identify target antigens for an improved enzyme immuno assay.
      Until such an assay is available, Western blotting can provide a specific tool
      for the diagnosis of B. caballi infections, particularly in cases of
      contradicting CFT and IFAT results.

PMID- 1399248
TI  - Sparganum proliferum: an overview of its structure and ultrastructure.
AB  - A detailed study of the structure and ultrastructure of Sparganum proliferum was
      made possible for the first time thanks to the successful in vitro and in vivo
      maintenance of this rare parasite. Although S. proliferum exhibits many of the
      classical tegumental and parenchymal structures previously described for other
      larval cestodes, these are either arranged in a distinct fashion or, in some
      cases, may be completely different. Among the latter and of special interest are
      the single or multiple parenchymal cavities, surrounded by tegument, which in
      some instances appear to act as a primitive digestive tract.

PMID- 1399249
TI  - The development and mortality of the free-living stages of Haemonchus contortus
      in laboratory culture.
AB  - Haemonchus contortus eggs were cultured in intact fecal pellets at various
      temperatures (5-35 degrees C) for 22 days. Temperature and relative humidity were
      kept constant throughout the incubation period. Nl larval development occurred at
      5 degrees C; peak third-stage larval recovery occurred at 20 degrees C. Egg
      mortality was an age-dependent phenomenon, whereas larval mortality remained
      constant irrespective of larval age. Development was characterized by a minimum
      development time followed by a transition to the next stage which occurred at a
      constant rate. All rates were temperature dependent. The minimum development
      times reported here are much less than those previously reported. Based on these
      results a mathematical model was used to describe the demography of the free
      living stages of H. contortus at various temperatures.

PMID- 1399250
TI  - Biology and pathogenicity of Eimeria spinosa Henry, 1931 in experimentally
      infected pigs.
AB  - A single-species isolate of E. spinosa from a diarrheic weaned pig was used to
      determine the endogenous development and pathogenicity of this swine coccidium.
      Seven out of 14 inoculated pigs developed endogenous stages or passed oocysts of
      E. spinosa in their feces. Immunosuppressive treatment with cyclophosphamide had
      no effect on the susceptibility to infection with E. spinosa in young pigs. The
      endogenous stages developed within the apical cytoplasm of the enterocytes lining
      the distal part of the villi in the posterior jejunum. The asexual development
      comprised three generations of meronts, which were seen at 5, 7 and 9 days post
      infection (DPI). Meronts of the first generation measured 6-8 microns and
      produced 10-14 merozoites 4-6 microns in length. The second generation of meronts
      measured 6-8 microns and contained 10-20 merozoites 4-6 microns in length. Third
      generation mature meronts (8-10 microns) on DPI 9 contained 12-20 merozoites
      measuring 5-7 microns, which were more crescent-shaped and less blunt than the
      merozoites at 5 and 7 DPI. Merogony continued after formation of the gametes and
      the first fully developed macrogametes (10-14 microns), microgametes (9-12
      microns), and oocysts were also seen at 9 DPI. The prepatent period was 8 or 9
      days, but the patent period was not determined. In the present study E. spinosa
      infection did not produce overt clinical signs. Pathological changes consisted of
      an inflammatory infiltration in the lamina propria of the posterior jejunum,
      Peyer's patches activation and sporadic erosions scattered at the villous tips.
      No villous atrophy in association with a large number of endogenous stages was
      observed.

PMID- 1399251
TI  - The importance of sculpin (Myoxocephalus scorpius) as intermediate host and
      transmitter of the sealworm Pseudoterranova decipiens.
AB  - A total of 186 sculpins (Myoxocephalus scorpius) were caught at Vega, Nordland,
      Norway, and examined for sealworm larvae (Pseudoterranova decipiens). Over 80% of
      the fish were infected. Very high infections were found with a maximum of nearly
      300 larvae in one sculpin. Infections of this magnitude have so far not been
      reported from sculpins or any other fish species of this size. The importance of
      the sculpin in the life cycle and in the transmission of P. decipiens to seals or
      other fish species is briefly discussed.

PMID- 1399252
TI  - Seasonal intensity of Angiostrongylus cantonensis in the intermediate host,
      Laevicaulis alte.
AB  - The slug, Laevicaulis alte, is a vector of Angiostrongylus cantonensis in the
      Greater Bombay area. The seasonal prevalence of A. cantonensis was investigated
      to determine the maximum intensity of the parasite in a field population
      occupying an area of approximately 400 m2. The maximum intensity of larvae was
      observed in the rainy months, June-November. Investigations showed that
      individual L. alte could tolerate an infecting dose of 150 first-stage A.
      cantonensis larvae before mortalities occurred.

PMID- 1399253
TI  - Responses of Echinostoma caproni miracidia to gravity, light, and chemicals.
AB  - In a four-tube vertical system, Echinostoma caproni miracidia exhibited a strong
      negative geotaxis which was dominated by a positive phototaxis. In horizontal
      chambers a positive phototactic response was also demonstrated. These miracidia
      showed a positive chemoresponse, as determined in phi-chambers, to glutamic and
      aspartic acids but not leucine. Positive responses were also elicited to snail
      conditioned water and sulfuric and acetic acids. Ammonia, Mg2+, and HCl produced
      no significant reactions. Responses of E. caproni and Schistosoma mansoni
      miracidia, both of which develop in Biomphalaria glabrata snails, were similar
      providing further evidence that miracidia mimic the behavioral patterns of
      compatible snail species.

PMID- 1399254
TI  - Natural Echinococcus multilocularis infection in a Norway rat, Rattus norvegicus,
      in southern Hokkaido, Japan.
AB  - Forty-two rats, Rattus norvegicus, captured at a garbage dump in southern
      Hokkaido, Japan, were examined, and one was found to be infected with
      Echinococcus multilocularis. The lesions were found in the liver, lung,
      mesenteric lymph nodes, greater omentum and also free in the abdominal cavity. No
      necrosis was observed in any of the lesions, and inflammatory reactions were
      mild. Protoscoleces were observed in the large liver cysts. A homogenate of these
      cysts, when transplanted into the abdominal cavity of three Mongolian gerbils and
      a rat, yielded numerous fully developed protoscoleces at 4-7 months post
      inoculation. Judging from this, it is postulated that the rat could become a
      natural intermediate host for E. multilocularis in this area.

PMID- 1399255
TI  - Nucleotide sequence of a cDNA from Onchocerca gibsoni encoding a novel repetitive
      antigen.
AB  - mRNA from uterine microfilariae of the cattle parasite Onchocerca gibsoni was
      used for the construction of cDNA libraries. A cDNA clone encoding an antigen
      recognized by serum from human individuals infected with O. volvulus was found to
      contain five copies of an 87 bp unit. These 87 bp units were present in the
      genome in high copy number as long tandem arrays. These are the first cDNA
      sequence data obtained directly from larvae of any Onchocerca species.

PMID- 1399256
TI  - An episode in the history of protein chemistry: Pehr Edman's method for the
      sequential degradation of peptides.

PMID- 1399257
TI  - Orthogonal solid-phase synthesis of a monobiotinylated analog of neuropeptide Y.
AB  - Analogs of Neuropeptide Y (NPY) were synthesized with conventional Boc/benzyl
      protective group strategy. Instead of Asn7 in the native sequence, Boc-Lys(Alloc)
      OH was incorporated. At the end of the synthesis the Alloc group was selectively
      removed by palladium-catalyzed hydrostannolysis and biotin coupled to the epsilon
      amino group of Lys7. After cleavage and characterization with plasma desorption
      mass spectrometry the N epsilon,7-biotinyl-[Lys7]-NPY and the nonbiotinylated
      analog [Lys7]-NPY were investigated as ligands to the NPY receptor from rat
      cerebral cortex. Both analogs were found to be high affinity ligands to the NPY
      receptor and bound with essentially the same affinity as unmodified NPY.

PMID- 1399258
TI  - Fmoc-amino acid chlorides in solid phase synthesis of opioid peptides.
AB  - Fmoc-amino acid chlorides were employed in the solid phase synthesis of the
      opioid peptides [Leu]enkephalin, [Leu]enkephalin amide, and dermorphin. The
      conventional polystyrene-based Merrifield resin or Wang's resin served as solid
      support. A binary salt of either triethylamine or diisopropylethylamine in the
      presence of 1-hydroxybenzotriazole or pivalic acid was used for acylation. The
      coupling rates were quite fast, being comparatively faster when 1
      hydroxybenzotriazole was used along with triethylamine or diisopropylethylamine.
      The peptides obtained in good yields showed, after purification, biological and
      spectral properties identical with those of the natural peptides.

PMID- 1399259
TI  - Potent agonists of growth hormone-releasing hormone. Part I.
AB  - Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH)
      with agmatine (Agm) in position 29 have been synthesized by the solid phase
      method, purified, and tested in vitro and in vivo. The majority of the analogs
      contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N
      MeTyr1. Some peptides contained one or more additional L- or D-amino acid
      substitutions in positions 2, 12, 15, 21, 27, and/or 28. Compared to the natural
      sequence of GH-RH(1-29)NH2, [Dat1,Ala15]GH-RH(1-28)Agm (MZ-3-191) and [D
      Ala2,Ala15]GH-RH(1-28)Agm (MZ-3-201) were 8.2 and 7.1 times more potent in vitro,
      respectively. These two peptides contained Met27. Their Nle27 analogs,
      [Dat1,Ala15,Nle27]GH-RH(1-28)Agm(MZ-2-51), prepared previously (9), and [D
      Ala2,Ala15,Nle28]GH-RH(1-28)Agm(MZ-3-195) showed relative in vitro potencies of
      10.5 and 2.4, respectively. These data indicate that replacement of Met27 by
      Nle27 enhanced the GH-releasing activity of the analog when the molecule
      contained Dat1-Ala2 residues at the N-terminus, but peptides containing Tyr1-D
      Ala2 in addition to Nle27 showed decreased potencies. Replacement of Ser28 with
      Asp in multi-substituted analogs of GH-RH(1-28)Agm resulted in a decrease in in
      vitro potencies compared to the parent compound. Thus, the Ser28-containing MZ-2
      51, and [Dat1,Ala15,D-Lys21,Nle27]GH-RH(1-28)Agm, its Asp28 homolog (MZ-3-149),
      possessed relative activities of 10.5 and 5.6, respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1399260
TI  - Conformational investigation of alpha, beta-dehydropeptides. Part III. Molecular
      and crystal structure of acetyl-L-prolyl-alpha, beta-dehydrovaline methylamide.
AB  - The crystal structure of Ac-Pro-delta Val-NHCH3 was examined to determine the
      influence of the alpha,beta-dehydrovaline residue on the nature of peptide
      conformation. The peptide crystallizes from methanol-diethyl ether solution at 4
      degrees in needle-shaped form in orthorhombic space group P2(1)2(1)2(1) with a =
      11.384(2) A, b = 13.277(2) A, c = 9.942(1) A, V = 1502.7(4) A3, Z = 4, Dm = 1.17
      g.cm-3 and Dc = 1.18 g.cm-3. The structure was solved by direct methods using
      SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The
      peptide is found to adopt a beta-bend between the type I and the type III
      conformation with phi 1 = -68.3(4) degrees, psi 1 = -20.1(4) degrees, phi 2 = 
      73.5(4) degrees and psi 2 = -14.1(4) degrees. An intramolecular hydrogen bond
      between the carbonyl oxygen of ith residue and the NH of (i + 3)th residue
      stabilizes the beta-bend. An additional intermolecular N...O hydrogen bond joins
      molecules into infinite chains. In the literature described crystal structures of
      peptides having a single alpha,beta-dehydroamino acid residue in the (i + 2)
      position and forming a beta-bend reveal a type II conformation.

PMID- 1399261
TI  - Crystal structure and conformation of a highly constrained linear tetrapeptide
      Boc-Leu-dehydro Phe-Ala-Leu-OCH3.
AB  - The conformation of a tetrapeptide containing a dehydro amino acid, delta ZPhe,
      in its sequence has been determined in the crystalline state using X-ray
      crystallographic techniques. The tetrapeptide, Boc-Leu-delta ZPhe-Ala-Leu-OCH3,
      crystallizes in the orthorhombic space group P2(1)2(1)2(1) with four molecules in
      a unit cell of dimensions a = 11.655(1) A, b = 15.698(6) A and c = 18.651(3) A V
      = 3414.9 A and Dcalc = 1.12 g/cm-3. The asymmetric unit contains one tetrapeptide
      molecule, C30H46N4O7, a total of 41 nonhydrogen atoms. The structure was
      determined using the direct methods program SHELXS86 and refined to an R-factor
      of 0.049 for 3347 reflections (I3.0(I). The linear tetrapeptide in the crystal
      exhibits a double bend of the Type III-I, with Leu1 (phi = -54.1 degrees, psi = 
      34.5 degrees) and delta ZPhe2 (phi = -59.9 degrees, psi = -17.1 degrees) as the
      corner residues of Type III turn and delta ZPhe2 (phi = -59.9 degrees, psi = 
      17.1 degrees) and Ala3 (phi = -80.4 degrees, psi = 0.5 degrees) residues
      occupying the corners of Type I turn, with delta ZPhe as the common residue in
      the double bend. The turn structures are further stabilized by two intramolecular
      4----1 type hydrogen bonds.

PMID- 1399262
TI  - Racemization studies in peptide synthesis through the separation of protected
      epimeric peptides by reversed-phase high performance liquid chromatography.
AB  - Separation of protected epimeric peptides, Z-Gly-Xaa-Xbb-OMe (where Xaa and Xbb =
      chiral amino acid residues), by reversed-phase HPLC was utilized for studying
      racemization in peptide synthesis. Thus, the following factors which might affect
      the extent of racemization during the coupling by the carbodiimide method were
      investigated: the combination of amino acid residues to be coupled, coexisting
      tertiary amine salts, and the relative configuration of the amino acid residues.
      The following points were revealed: the combination of bulky residues at the
      coupling site results in extensive racemization in a polar solvent such as DMF,
      the amine hydrochlorides cause less racemization than the p-toluene-sulfonates in
      DMF, and the influence of relative configuration differs depending on the solvent
      and the individuality of the amino components. Furthermore, the racemization
      suppressing effect of some additives in the carbodiimide method was reevaluated
      by employing the same procedure.

PMID- 1399263
TI  - Effect of copper(II) chloride on suppression of racemization in peptide synthesis
      by the carbodiimide method.
AB  - Copper(II) chloride was found to be an extremely efficient racemization
      suppressing additive in the DCC method as compared with the hitherto known ones,
      by employing the model coupling Z-Gly-L-Val-OH + H-L-Val-OMe in DMF. Although
      some other copper salts also had a profound effect, copper(II) chloride was the
      best from the viewpoint of both racemization suppression and coupling efficiency.
      The effectiveness of copper(II) chloride was further confirmed by employing the
      EDC-mediated couplings of Z-Gly-containing dipeptides with amino acid esters or
      dipeptide esters, and those of Z-L-Ala (or L-Val)-L-Val-OH with amino acid esters
      or dipeptide esters. In almost all the cases studied, no detectable amount (less
      than 0.1%) of epimer was observed by the HPLC analysis in the presence of
      copper(II) chloride. This was also the case even with an extremely stringent
      coupling system Z-L-Pro-L-Val-OH + H-L-Pro-OMe. With reference to the mechanism
      of racemization suppression, it was found that copper(II) chloride has a strong
      ability to suppress the racemization of the 5(4H)-oxazolone, which may be formed
      from an activated carboxyl component during the coupling.

PMID- 1399264
TI  - Isolation and characterization of glycosylated and non-glycosylated prolactins
      from alligator and crocodile.
AB  - Two molecular forms of prolactin (PRL), glycosylated and non-glycosylated, were
      isolated from pituitary glands of two reptiles, alligator and crocodile. The
      reptilian PRLs were extracted under alkaline conditions from the precipitate
      obtained after pituitaries were first extracted with 0.25 M sucrose, 1 mM
      NH4HCO3, pH 6.3. Purification was performed by ion exchange chromatography on DE
      52, gel filtration on Sephadex G-75 superfine, and reversed phase high
      performance liquid chromatography. Two forms of both alligator and crocodile PRL,
      designated PRLI and PRLII, with molecular weights of 26,000 and 24,000 were
      isolated. Alligator and crocodile PRLI and PRLII were stained specifically in
      immunoblots with anti-sea turtle PRL and anti-ostrich PRL. Sequence analysis
      revealed that both forms of alligator and crocodile PRLs consisted of 199 amino
      acid residues with a glycosylation consensus sequence (Asn-Ala-Ser) at position
      60 in alligator and crocodile PRLs with a molecular weight of 26,000 (PRLI). In
      contrast, Thr was substituted for Asn at position 60 in the PRLs with a molecular
      weight of 24,000 (PRLII). The sequences of alligator PRLs differed from crocodile
      PRLs only in position 134: Val for alligator PRLs and Ile for crocodile PRLs.
      There is a high degree of structural conservation between the reptilian PRLs
      isolated in this study and avian PRL; each showed 92% sequence identity with
      chicken PRL and 89% with turkey PRL.

PMID- 1399265
TI  - Crystal structure and molecular conformation of achatin-I (H-Gly-D-Phe-Ala-Asp
      OH), an endogenous neuropeptide containing a D-amino acid residue.
AB  - In order to investigate the active conformation of achatin-I (H-Gly-D-Phe-Ala-Asp
      OH), an endogenous neuropeptide from the Achatina fulica ganglia, its crystal
      structure and molecular conformation were analysed by the X-ray diffraction
      method. Crystals from methanol/dioxane are monoclinic, space group P2(1) with a =
      5.083(1), b = 9.125(1), c = 20.939(3) A, beta = 94.73(1) degrees. The structure
      was solved by direct methods and refined to R = 0.051 for 1714 independent
      reflections with /Fo/ greater than sigma (Fo). The molecule exists as a
      zwitterion with the Gly N-terminal end protonated and Asp beta-carboxyl
      deprotonated; the C-terminal of Asp is in a neutral state. The molecule takes a
      kind of beta turn structure with the D-Phe-Ala residues at the corner of the
      bend. This turn conformation is primarily formed by the strong intramolecular
      hydrogen bonds of NH(Gly)...O delta 1 (Asp) and NH(Asp)...O delta 1 (Asp) pairs,
      thus forming a 15-membered ring structure. Judging from the published data
      concerning the structure-activity relationship, this turn conformation may
      reflect an important feature related to the neuroexcitatory activity of achatin
      I.

PMID- 1399266
TI  - Studies on cell-clearing activity in alpha-lactalbumin. Effects of calcium
      removal on activity and conformation.
AB  - Effects of calcium removal on the cell-clearing activity of alpha-lactalbumin
      (alpha-LA) and concomitant changes in conformational structure have been
      investigated as part of a continuing study of the activity found earlier
      [McKenzie, H.A. & White, F.H., Jr. (1987) Biochem. Int. 14, 347]. This activity
      is similar to that of lysozyme, whereby lysis of the bacterial cell wall is
      catalyzed. However, the specific activity of alpha-LA is on the order of 10(-6)
      that of lysozyme. Under conditions where activities of apo and native alpha-LA
      were approximately linear functions of the protein concentration, the maximal
      ratio of apo to native activity was 5.7:1, determined by comparison of second
      order velocity constants. The CD spectrum of apo alpha-LA is intermediate between
      that of the A state and the native protein. By NMR, the conformation of apo alpha
      LA is similar to, but distinctly different from, that of the native protein. The
      apo form did not revert completely to the native state when Ca(II) was
      resupplied, consistent with a role for this cation in folding. It is suggested
      that the activity increase may result from a diminished constriction of the
      "cleft" region in alpha-LA.

PMID- 1399267
TI  - "Carba" peptide bond surrogates. Different approaches to Gly-psi(CH2-CH2)-D,L-Xaa
      pseudo-dipeptide units.
AB  - Racemic "carba" pseudo-dipeptide units such as Gly-psi(CH2-CH2)-D,L-Xaa were
      obtained either through the Horner-Emmons condensation of N-tert.
      butyloxycarbonyl-beta alaninal with the appropriate substituted triethyl
      phosphonacetate, or from commercially available 3-carbethoxy-2-piperidone.

PMID- 1399268
TI  - Continuous flow synthesis of peptides using a polyacrylamide gel resin
      (Expansin).
AB  - The continuous flow syntheses of endothelin 1, proendothelin 2, ATP binding site
      of the CDC2 kinase 3, and fragment 18-30 of an actin 4, have been performed by
      using a polyacrylamide gel resin Expansin (about 0.6 mmol NH2/g) with the
      glycolamidic ester handle as labile anchorage. In addition, we report here a
      method of air oxidation which reduces the formation of side-products related to
      the formation of intermolecular disulfide bridges.

PMID- 1399269
TI  - Survey of conformational role of ester bonds in a cyclic depsipeptide. Study on
      cyclo(-L-Ala-L-Hmb-)2 by energy calculation and NMR spectroscopy.
AB  - The effect of ester bond on the conformation of peptide molecule was studied by
      designing and synthesizing a model tetradepsipeptide cyclo(-L-Ala-L-Hmb-)2 and by
      analyzing the conformation both theoretically and experimentally. Theoretical
      analysis showed that both ester and peptide bonds in the calculated low-energy
      conformations within 3 kcal/mol of the global minimum take a trans but distorted
      configuration. The distortion is larger in ester bonds than in peptide bonds.
      Further, the four carbonyls project from one side of the plane of the cyclic
      backbone, whereas the side chains project from the other side. These results are
      consistent with the experimental results obtained by NMR measurement; first, the
      coupling constant deduced from 1H-NMR species in DMSO-d6 is consistent with the
      dihedral angles of the calculated low-energy conformations; second, results of
      NOE measurement can reproduce the calculated configuration of the carbonyls and
      side chains. From the consistency between theoretical and experimental results,
      it is concluded that this model tetradepsipeptide takes an all-trans backbone
      conformation in solution and this backbone conformation is stabilized by large
      distortion in the ester bond, which compensates the strain resulted from the 12
      membered cyclic backbone structure consisting only of L-residues.

PMID- 1399270
TI  - Use of tetrabutylammonium salts of amino acids in peptide synthesis.
AB  - Tetrabutylammonium (TBA) salts of amino acids and peptides have increased
      solubility, as compared with that of alkali metals salts, in organic solvents. We
      have compared the reaction rates for tripeptide formation in methylene chloride
      from Boc-Gly-Phe activated with various phenols, N-oxysuccinimide and azide, and
      TBA-salt of tryptophan, as well as Trp-OCH3. H-Trp-O-.TBA+ as an amino component
      significantly accelerates the rate of reaction. Although a significant degree of
      racemization has been found, the use of TBA-salt of amino acids and peptides is
      justified in many cases due to high conversion rates.

PMID- 1399272
TI  - Racemization free coupling of peptide segments. Synthesis of an insect
      neuropeptide.
AB  - The total synthesis of the insect neuropeptide derivative Z-Gly-Gly-Ser-Leu-Tyr
      Ser-Phe-Gly-Leu-NH2 has been carried out by a convergent solid phase strategy.
      For the coupling of the N-terminal pentapeptide to the C-terminal tetrapeptide,
      three different methods were assayed. Racemization of the acyl activated amino
      acid during the fragment condensation reaction was monitored by HPLC. Best
      results were obtained by enzymatic coupling in a low water containing media using
      adsorbed alpha-chymotrypsin. An optically pure product was obtained in 82% yield
      after 1 h of reaction. Chemical methods such as DIC/HOBt and BOP/HOBt/NMM always
      rendered highly optically impure products containing 10-20% of the D-epimer.

PMID- 1399271
TI  - Peptide inhibitors of E. collagenolyticum bacterial collagenase--effect of N
      methylation. Consequences on biological activity and conformational properties.
AB  - Peptide inhibitors of E. collagenolyticum bacterial collagenase, HS-CH2-CH2-CO
      Pro-Yaa (Yaa = Ala, Leu, Nle), have been N-methylated at the Yaa position. The N
      methylation slightly increases the inhibitory potency of the modified peptides as
      compared to the parent compounds. The conformational effects of the N-methylation
      have been investigated by both 1H 2D-NMR and molecular mechanics energy
      minimization. Three low-energy conformers have been predicted for the
      unmethylated parent compounds (Yaa = Ala, Leu, Nle). They are characterized by
      the psi value of the central proline residue: psi Pro = 150 degrees (trans'
      conformation), psi Pro = 70 degrees (C7 conformation) and psi Pro = -50 degrees
      (cis' conformation). The N-methylation has been found to strongly increase the
      energy of the C7 conformer and to a less extent the energy of the cis' conformer.
      This leaves the trans' conformation as the only low-energy conformer. The ROESY
      experiments have established that both the N-methyl peptides and the parent
      compounds adopt the same preferred backbone conformation in water solution, i.e.
      the trans' conformation. Based on these results, the activities of the N-methyl
      peptides are discussed and a possible conformation of the inhibitor in the bound
      state is proposed.

PMID- 1399273
TI  - Novel cyclization chemistry especially suited for biologically derived,
      unprotected peptides.
AB  - A novel method is described for the cyclization of peptides--or segments of
      polypeptides--which requires a free N-terminal alpha-amino group and a distal
      amino acid residue containing a nucleophilic side chain. The reaction is
      conducted in two steps, both in the aqueous phase. The first step involves
      acylation of the N-terminal alpha-amino group with iodoacetic anhydride at pH 6.
      This acylation reaction has greater than 90% specificity for peptide alpha-amino
      groups and gives no alkylation of Arg, His, Lys or Met by the iodoacetate side
      product (R. Wetzel et al., Bioconjugate Chem., 1, 114-122, 1990). In the second
      step, the acylation reaction mixture or the isolated iodoacetyl-peptide is
      incubated at room temperature to give the cyclic peptide formed by reaction of
      the nucleophilic side chain with the iodoacetyl moiety. The pH dependence of the
      cyclization reaction by Met, Lys, Arg or His is consistent with the pKa of the
      nucleophilic side chain. Thus, peptides containing Met plus other nucleophilic
      amino acids should preferentially cyclize via Met at low pH. In this paper,
      preparation of cyclic peptides containing 3-6 amino acids is described; the full
      range of ring sizes and sequences which can undergo this cyclization has not been
      further explored. Preliminary results suggest that this method is also fairly
      general with respect to the amino acid sequence being cyclized. The reaction
      appears to be particularly suited for cyclization via Lys and Met side chains.
      All of the cyclized products are sufficiently stable for many biological
      applications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399274
TI  - Design of hydropathically complementary peptides for Big Endothelin affinity
      purification.
AB  - Molecular recognition between Big Endothelin (Big ET) and a computer generated
      peptide hydropathically complementary to Big ET[16-29] sequence has been studied
      by analytical high performance liquid affinity chromatography (HPLAC), circular
      dichroism (CD) and nuclear magnetic resonance (NMR) experiments. Specific binding
      was observed between solid support immobilized complementary peptide and Big ET[1
      38], [1-32], and [16-32], but not with Big ET fragments [1-21], [16-21], [22-32],
      and [22-38], obtained by chymotrypsin proteolytic degradation. Selectivity in the
      recognition process was clearly demonstrated by the ability of complementary
      peptide affinity column to purify the Big ET molecule from complex peptide
      mixtures, even when present in very low concentrations. Similar selectivity was
      evidenced with the Big ET fragment [16-32], [NH2-HLDIIWVNTPEHIVPYG-COOH]
      containing the entire hydropathically complementary sequence. Binding was
      followed by marked spectroscopic changes, as monitored by circular dichroism and
      one- and two-dimensional nuclear magnetic resonance experiments. The NMR spectra
      of the complementary peptides 1:1 mixture showed variations in the chemical
      shifts of proton resonances in several residues, both in the main chain (amide
      protons) and in the side chains (aliphatic and aromatic protons). These data
      support the hypothesis of a multilocalized type of interaction between
      complementary peptides, where many residues along the peptide chains participate
      in co-operative stabilizing contacts in the forming complex.

PMID- 1399275
TI  - Affinity enhancement of complementary peptide recognition.
AB  - A peptide hydropathically complementary to Big Endothelin [Big ET] residues 16-29
      has been synthesized in a multimeric form starting from an octadentate polylysine
      core, essentially in a way similar to the procedure used for the production of
      multiple antigenic peptides [MAP's]. Interaction between the multimeric
      complementary peptide [8 delta ET] and the Big ET fragment 16-32 containing the
      target complementary region, also synthesized in a multimeric form [8ET], was
      evaluated by analytical high performance affinity chromatography and solid phase
      binding assays. While the binding interaction between the monomerics peptide pair
      was in the micromolar range, the recognition between the corresponding multimeric
      form was characterized by enhanced binding affinity of at least two orders of
      magnitude. In solution, complex formation between multimeric complementary
      peptide and target Big ET sequence in the monomeric and multimeric form was
      accompanied by precipitation at concentrations higher than 0.5 mg/mL and 0.1
      mg/mL, respectively. Polyclonal antibodies raised against the multimeric target
      sequence recognized multimeric and monomeric ET target sequences with binding
      affinities similar to binding affinities exhibited by the multimeric
      complementary peptide. Multimerization of hydropathically complementary peptides
      could provide an improved opportunity to measure and thus probe quantitative
      binding properties of complementary peptides.

PMID- 1399276
TI  - The psychoanalytic theory of change.
AB  - The concept of change by psychoanalysis has undergone an historical process
      related to the course and development of psychoanalytic theory. Change has
      changed from an effect on symptoms, to underlying etiologic conflicts, to
      background character, to the functioning of psychic structural systems. The
      psychoanalytic process does not overlap with the process of change. The former
      may be present without the latter. The will to recover is accompanied by the
      unconscious need to cover. The methodology of change is examined with regard to
      process, agent(s), and intrapsychic results. Every analysis is a training and
      supervised analysis. With increasing autonomy of the ego, the patient,
      identifying with the analysing functioning of the analyst, becomes his own
      analyst. The theory of change is related to the psychoanalytic theory of neurosis
      of which it is part, and differs in alternative theories extant today. The
      dynamic occurrences I have described as bringing about change rest upon my view
      of 'total composite psychoanalytic theory' as evolved to the present.

PMID- 1399277
TI  - Interpretation between determinism and hermeneutics: a restatement of the
      problem.
AB  - The author opposes the two principal conceptions of interpretation: the
      deterministic conception predominant in Freud, in which the present is determined
      by the subject's actual past; and the creative hermeneutic conception, which
      traces its origins back not only to Heidegger and Ricoeur but also to Jung; in
      the latter view, interpretation cannot but be retroactive, assigning significance
      to a meaningless past. The author shows that Freud, in exactly the same way as
      the hermeneuts in the opposing camp, remains the prisoner of the antithesis of
      factual reality and a purely subjective interpretation close to fantasy. He lacks
      a third category, that of the message whose meaning is immanent, in particular
      taking the form of the mostly non-verbal sexual messages conveyed by the adult to
      the small child. The development of the human individual is to be understood as
      an attempt to master, to translate, these enigmatic, traumatizing messages.
      Analysis is first and foremost a method of deconstruction (ana-lysis), with the
      aim of clearing the way for a new construction, which is the task of the
      analysand.

PMID- 1399279
TI  - From acting out to words and meaning.
AB  - This paper presents an explanation and illustration of the behavioural phenomenon
      of concretization through acting out. The phenomenon refers to the realization of
      fantasies and psychic conflicts pertaining to the traumatic past of Holocaust
      survivor parents, which might have been transmitted to the next generation
      narratively or beyond words. I have illustrated this phenomenon by material taken
      from the first stages of the analysis of a young man who shot and wounded his
      father during the latter's attempt to save him from suicide. The analytic
      experience facilitated the stabilization of ego boundaries and the emergence of a
      more secure sense of self.

PMID- 1399278
TI  - An infantile trauma, a trauma during analysis, and their psychic connexion.
AB  - The case described here involves a patient who suffered a trauma while in the
      final stages of a successful analysis. The trauma temporarily eclipsed many of
      the gains of the analysis. Surprisingly, however, the regression caused by this
      trauma led to further lifting of repression. This resulted in new information,
      greater affective expression and a greater therapeutic gain than would have
      otherwise been possible. The clinical technique devised for this special
      situation is described.

PMID- 1399280
TI  - Love and male impotence.
AB  - This paper deals with male impotence in relation to love. A detailed clinical
      presentation attempts to show how the symptom was embedded in faulty processes of
      separation-individuation, whereby regression in the service of intercourse,
      passion and love is hindered by the fears and fantasies underlying merging
      experiences. These problems are examined as they appear interwoven in
      transference and counter-transference phenomena. The clinical case presentation
      is followed by a discussion of different forms of male impotence from a more
      general viewpoint; its relation not only to castration and phallic anxiety, but
      also to earlier developmental aspects. Finally, some reflections about male and
      female gender differences in relation to symbiotic experience.

PMID- 1399281
TI  - The Isakower phenomenon revisited: a case study.
AB  - The Isakower phenomenon is a situation in which an individual typically
      experiences perceptions of enlargement or thickening, altered states of
      consciousness, sensations of floating, and impressions of the emergence and
      disappearance of an oral mass. This paper defines the phenomenon, reviews the
      literature, and describes a case in which a patient experienced it. The patient
      manifested the phenomenon symptomatically in the aftermath of a toxic state, and
      the elements were analysed for several years. There was support for Isakower's
      original thesis that the regressive states serve to defend against threatening
      incestuous fantasies. However, the Isakower phenomenon in this patient was the
      result of a multiplicity of determinants, largely defensive, involving many
      developmental levels.

PMID- 1399282
TI  - Problems in the psychoanalysis of certain narcissistic disorders.
AB  - This paper considers the psychopathology and treatment of a particular group of
      narcissistic disorders which can be characterized by their use of 'simulation' in
      their attempt to resolve the conflicts of the Core Complex. The invasive,
      narcissistic mother's demand for success is responded to with an evident
      compliance but with a covert rebellion manifested in failure, accompanied by
      intense feelings of shame and low self-esteem. This is seen in the analysis in
      the patient's apparently positive response being followed by a Negative
      Therapeutic Reaction. The structure is seen to be as much concerned with
      protecting the mother from the infant's destructiveness as it is with protecting
      the infant from the colonizing mother (cf. Winnicott's 'False Self'). What is
      regarded as the hallmark of narcissistic disorders, namely shame, is found to be
      part of a defensive structure concerned with the exclusion of extreme violence
      and intolerable guilt. The significance of the father is discussed. Difficulties
      that arise in the analysis of such patients are considered.

PMID- 1399283
TI  - The child and/or the picture. Motherhood and creativity: their vicissitudes.
AB  - The development of this clinical case, that of a young mother who was a painter,
      illustrates the link between motherhood and sublimated creativity. The importance
      of male identifications, the difficulties of identification with the mother and
      the guilt connected with penis envy are emphasized. Castration anxiety is
      attached to the child, experienced as a penis equivalent. Anal fixation also
      plays a crucial part, aggravating the refusal of an excessively guilt-ridden
      genital sexuality. The vicissitudes and conditions of female sublimation are
      discussed.

PMID- 1399284
TI  - The dialectically constituted/decentred subject of psychoanalysis. I. The
      Freudian subject.
AB  - Central among the irreducible elements that define a psychoanalytic understanding
      of man is Freud's conception of the subject, and yet this theme remained a
      largely implicit one in Freud's writing. The Freudian conception of the process
      by which the subject is constituted is fundamentally dialectical in nature and
      involves the notion that the subject is created and sustained (and at the same
      time decentred from itself) through the dialectical interplay of consciousness
      and unconsciousness. The contribution of psychoanalysis to a theory of
      subjectivity involves the formation of a concept of the subject in which neither
      consciousness nor unconsciousness holds a privileged position in relation to the
      other; the two coexist in a mutually creating, preserving and negating
      relationship to one another. The principle of presence-in-absence and absence-in
      presence subtends the dialectical movement between conscious and unconscious
      dimensions of subjectivity.

PMID- 1399285
TI  - Mourning and erotic transference.
AB  - This article proposes that the clinical mourning process is a critical factor in
      transforming an aggressively-laden erotic transference, and its potential for use
      as resistance, into a conscious erotic transference that progressively mobilizes
      the psychoanalytic treatment process. A psychoanalytic case is used to illustrate
      that the mourning of the pre-oedipal object allows an erotic transference to
      emerge into consciousness in treatment. The case also demonstrates that the
      erotic transference takes the form, not only of desiring, but also of mourning
      the oedipal level object. The case serves as a case in point in illustrating that
      erotic transference appears in cases in which female analysts treat male
      analysands. Further, it illustrates that erotic transference remains a primarily
      object-related phenomenon as opposed to being a merely narcissistic phenomenon.
      Finally, it illustrates the course of working through the erotic transference in
      an analytic treatment in which the therapeutic object relationship facilitates
      mourning.

PMID- 1399286
TI  - The countertransference position and the countertransference.
AB  - The concept of countertransference assumes different meanings depending on the
      context in which it is used. And yet it is an essential concept whose absence
      would have important theoretical and practical consequences. At the risk of
      increasing the psychoanalytic Babel, I propose the concept of the counter
      transferential position which, in my view, allows a better understanding of the
      multiple determinations which impinge upon the analyst during the session. In a
      brief clinical example, I examine a 'countertransferential symptom' and the
      analyst's function of 'listening to listening'.

PMID- 1399287
TI  - On the survival function of autistic manoeuvres in adult patients.
AB  - This paper highlights features of the work on autism of Tustin and others
      pertaining to the analysis of adult patients. Several clinical illustrations from
      the analysis of neurotic, borderline and psychotic patients emphasizing the
      survival function of autistic shapes, objects and delusions are presented. The
      need for further discrimination between autistic states of mind and other
      primitive mental states is recommended.

PMID- 1399288
TI  - Transference and countertransference. From deployment against feelings of loss-
      through psychotic regressions--to a better capacity to feel and to mourn.
AB  - Problems relating to the treatment of deployed patients are described and
      discussed through the case material on David Fisher. Since the deployments are
      not merely the defences or resistances we meet in neurotics, but a way of life
      with which these persons are strongly identified--deploying forces against the
      subjective experience of psychic pain--a different approach is felt to be
      required. I call this an affect-focused approach. Some of the major curative
      factors which have been found useful in persons with deployment are described and
      illustrated.

PMID- 1399289
TI  - John D. Sutherland (1905-1991).

PMID- 1399290
TI  - The wish for a sex change.

PMID- 1399291
TI  - Countertransference.

PMID- 1399292
TI  - [Management of patient flows. Evaluation of the hospital supply].
AB  - To propose a decision analysis model from the analysis of care process and
      management indicators. After defining institutional purpose and with the
      Hospital's structural size and activity analysis, this model allows to know the
      hospital supply related to demand. According to the knowledge of the frequency of
      the activity to perform, it could be possible to avoid inefficacy.

PMID- 1399293
TI  - [Length of stay in the hospital emergency department].
AB  - We evaluated the overall time spent by patients in the emergency department as
      well as the time employed in the different steps of emergency care and their
      relationship to patient's diagnosis. Data from 2421 patients, randomly selected,
      amongst those who attended hospital's emergency department units between november
      22-28th 1990 were collected data in a specially designed form. The mean time
      required for examination was 13 minutes and this procedure was carried out, in
      average, 18 minutes after admission. The mean length of stay in emergency area
      was 127 minutes with a significant increase in those cases rated as "true"
      emergencies.

PMID- 1399294
TI  - [Risk for injuries in traffic accidents among drivers under the effect of alcohol
      in Navarra].
AB  - We conducted a retrospective analysis of the levels of alcohol in the blood of a
      group of 54 drivers who required hospital emergency care after having suffered a
      traffic accident on roads in the Health Area III of Navarra (Spain) from June to
      September 1989, and compared them to another group of 219 drivers, not victims of
      traffic accidents, submitted to the breathalyser (test of alcoholaemia) on the
      roads of the same Health Area over the same period of time. In the group of 54
      accident victims, the median alcoholaemia was 100 mg/dl, with a quartile
      deviation of 88 mg/dl, and the percentage of positives (alcoholaemia equal to or
      greater than 80 mg/dl) was 50.9%. In the group of 219 drivers not victims of
      traffic accidents, the median alcoholaemia was 16 mg/dl, the quartile deviation
      18.5 mg/dl and the percentage of positive alcoholaemia was 1.8%. Drivers with a
      level of blood alcohol equal to or greater than 80 mg/dl have an estimated risk
      (Odds Ratio) of being injured in a traffic accident 55.82 times higher than
      drivers with a lower level.

PMID- 1399295
TI  - [The effectiveness of breast cancer screening in our country].
AB  - The aim of this paper is to review the current state of breast cancer screening
      in our country, as well as to discuss the most appropriate approaches for its
      development. Firstly, the impact of breast cancer in Spain is presented, as well
      as the current evidence about the efficacy of the screening. The major programs
      and initiatives addressed to promote screening are described. Finally, a few
      recommendations are given in order to achieve that breast cancer screening be,
      not only efficacious, but also effective. It is concluded that it is necessary
      that health and professional authorities coordinate and monitor breast cancer
      screening programs.

PMID- 1399296
TI  - [Alcoholism in hospitals in Valladolid].

PMID- 1399297
TI  - [Age-period-cohort analysis of mortality caused by ischemic cardiopathy in Spain
      1965-1985].
AB  - With the objective of studying the temporal evolution of ischaemic cardiopathy
      (IC), or coronary heart disease mortality, in Spain, we carried out a cohort
      analysis with conventional graphic techniques and modern statistical methods.
      This permits better understanding and quantification of the age-period-cohort
      effects and identification of the potential factors operating upon them. To this
      end, loglineal (Poisson regression) models were constructed of the IC mortality
      rates for both sexes, using the GLIM package, in which the regression
      coefficients are the natural Relative Risk (RR) logarithms of the various age
      groups (35-74 years), period of death (1970-1985) and birth cohort (1985-1960)
      with respect to the reference group mortality, controlled by the effect of other
      groups. In respect of the results, the maximum RR value corresponds to decrease
      year 1975, and falls progressively to 1985, though at all times remaining above
      the 1970 value. The effect of 1985, though less than 1980, does not present
      significant differences from the latter. Nevertheless, no clear cohort effect was
      found. As a probable explanation for the pattern observed, this would suggest
      recent changes in life style and in medical attention. There is a discussion of
      the consistency of the models selected with the graphical results and with
      present knowledge of the natural history of IC and with the evolution of its
      determining factors, together with validation of the models. In summary, the IC
      mortality patterns observed show an increase up to the mid-seventies, and
      stabilization from that date onwards, in all age and sex groups, which is
      consistent with an age-period effect.

PMID- 1399299
TI  - Childhood deafness in Malaysia.
AB  - One hundred and fifty-five children with childhood deafness were examined over a
      period of 4 years in order to assess the aetiology of hearing disorder. In 21
      (13%) children, deafness was a sequel of meningitis. Perinatal pathology
      accounted for 34 (22%) cases. The aetiology of deafness was unknown in 44 (28.4%)
      children. The percentage of unknown causes can be reduced if the deafness is
      detected early. Hearing loss was diagnosed only in 30 (19%) children by the age
      of 2 years. The early detection of deafness can be achieved by screening the high
      risk infants and educating the general practitioners and health assistants.

PMID- 1399298
TI  - On criteria for hearing impairment in children.
AB  - As objective criteria concerning hearing impairment/disability may be poorly
      related to the behavioral patterns of children with hearing deficits, the present
      investigation was performed. A consecutive series of 172 children, who were
      examined for the first time at the Audiological Department, was subdivided
      according to age into two groups: one comprising 98 children at an age from 49 to
      84 months, the other comprising 74 children greater than 84 months of age. This
      second group is supposed to complain of hearing problems if present, and thus
      constitutes a reference group. Using the criterion for hearing impairment: BEHL
      0.5-4 kHz greater than 20 dB HL, the data demonstrated that the frequency of
      correct and false positive suspicion (detection) of a hearing impairment is
      similar in parents and professionals with an observer sensitivity of 88%. In
      addition the frequency of suspicion in parents and professionals in relation to
      degree of hearing loss corresponds to the frequency of hearing problems, as
      experienced in the reference group of older children. A certain discrepancy
      exists between the applied criterion of BEHL 0.5-4 kHz greater than 20 dB and the
      hearing level resulting in deviating behavioral pattern or experienced hearing
      deficit in children. This may be ascribed to the predominantly conductive hearing
      loss in the examined sample. It is concluded that additional investigations on
      criteria for hearing impairment/disability, including also children with
      sensorineural hearing loss should be undertaken.

PMID- 1399300
TI  - Parental smoking and persistent otitis media with effusion in children.
AB  - A total of 163 children were entered into a case-control study to determine
      whether any causal relationship exists between otitis media with effusion (OME)
      requiring grommet insertion and parental smoking. One hundred children with
      persistent OME formed the case group and 63 children with normal ears formed the
      control group. The prevalence of parental smoking in each group was then
      compared. Information was collected by questionnaire and further details about
      the subjects with regard to surgery of the upper respiratory tract were also
      gathered. Analysis of findings in this study and previous reports has failed to
      demonstrate a significantly increased prevalence of smoking in at least one
      parent, amongst children with persistent otitis media with effusion requiring
      surgical intervention.

PMID- 1399301
TI  - Medical treatment of chronic suppurative otitis media without cholesteatoma in
      children--a two-year follow-up.
AB  - A prospective long-term study was carried out in 48 infants and children with
      chronic suppurative otitis media without cholesteatoma treated initially with
      wide spectrum intravenous antibiotics and suction and debridement. Patients were
      followed for a period of two years. All children were cured after completion of
      therapy. At 3 and 6 months follow-up 75% of the children were still free of
      discharge and at 12, 18 and 24 months the proportion of dry ears dropped to 71%,
      66% and 52%, respectively. Eighty percent of all recurrences developed already
      during the first 6 months of follow-up. Pseudomonas aeruginosa was the most
      common pathogen isolated, both in the initial and recurrent bouts of the disease,
      and was commonly associated with other pathogens. Children with early
      reappearance of ear discharge were less likely to benefit from further
      antimicrobial or surgical treatment. The recurrence rate was not affected by the
      antibiotic regimen, age, duration of drainage before treatment or the presence of
      granulation tissue. No intracranial or intratemporal complications were observed
      during the follow-up period.

PMID- 1399302
TI  - Fiberoptic examination of the nasal cavity and nasopharynx in children.
AB  - In this prospective study, a flexible fiberoptic nasolaryngoscope with color
      video camera was used to examine the nasal cavity and nasopharynx in 180
      pediatric patients. The relative size of the adenoid tissue was judged by
      endoscopy, which lead to a classification into 3 types according to the distance
      from the vomer to the adenoid tissue. The condition of the nasopharyngeal orifice
      of the Eustachian tube was also described and differentiated into 3 types
      relating to the condition of adenoid tissue. Assessment was performed by
      correlating these measurements with the tympanogram, lateral X-ray and clinical
      complaints. The authors conclude that: (1) fiberoptic examination allows direct
      visualization of the size and condition of the adenoid tissue, as well as of the
      condition of the nasopharyngeal orifice of the Eustachian tube. (2) The size of
      the adenoid tissue correlates very well with the nasal obstruction complaints as
      well as with the type of tympanogram. (3) The condition of the nasopharyngeal
      orifice of the Eustachian tube significantly corresponds with the type of
      tympanogram. (4) For the indication of adenoidectomy, fiberscopy gives more
      accurate information than standard X-ray. (5) With a correct choice of
      premedication and local anesthesia, it is a minor invasive technique which is
      very well tolerated by children. It is possible in all cases, provided it is
      performed by a skilled endoscopist and preceded by careful explanation to the
      child. (6) Finally, thanks to the possibility of direct visualization of the
      fiberscopic image via a monitor, it allows a better explanation of the indication
      for adenoidectomy to the child's parents.

PMID- 1399303
TI  - Change in velopharyngeal valving after speech therapy in cleft palate patients. A
      videonasopharyngoscopic and multi-view videofluoroscopic study.
AB  - Thirty-one cleft palate patients with velopharyngeal insufficiency and
      compensatory articulation in association with hypernasality after palate closure
      were studied. Videonasopharyngoscopy and multi-view videofluoroscopy were
      performed to all patients before and after speech therapy for correcting
      compensatory articulation. The ratios of movement of velopharyngeal structures
      were significantly increased after compensatory articulation had been corrected.
      Furthermore, the size of the gap at the velopharyngeal sphincter during closure
      was significantly reduced. The results in this study support the statement that
      articulation disorders in association with hypernasality in cleft palate patients
      should be corrected prior to the implementation of surgery for velopharyngeal
      insufficiency after palate closure.

PMID- 1399304
TI  - Body growth in relation to tonsillar enlargement and tonsillectomy.
AB  - Severe airway obstruction caused by tonsillar enlargement can result in
      disturbances in body growth. The effect of this interference and of tonsillectomy
      in the child with only moderate symptoms have been less satisfactoril evaluated.
      In this study, 122 children with symptoms and signs of tonsillar obstruction were
      investigated concerning the height and weight before and after tonsillectomy.
      None of the individuals demonstrated cardiopulmonary complications of tonsillar
      obstruction. Altogether 10% of the children exhibited abnormalities in body
      weight and/or length prior to surgery. Especially during the first postoperative
      year, the weight and height gain exceeded the expected in 75% of the patients.
      The accelerated weight gain increased with tonsil size, but there was no relation
      to the extent of difficulties in swallowing or sleeping disruptions. The results
      support the hypothesis that tonsillar hypertrophy frequently is associated with
      disturbances in body growth and that this is seldom demonstrable prior to
      tonsillectomy.

PMID- 1399305
TI  - Swallowing disorders in a population of children with cerebral palsy.
AB  - One of the disabilities in patients with cerebral palsy (CP) is dysphagia. To
      establish the prevalence of dysphagia in a population of children with CP, and to
      determine if any factors are related to dysphagia, we studied 56 CP patients, 5
      21 years, enrolled in a primary school for the disabled. Fifteen patients (27%)
      had either radiographic or clinical evidence of dysphagia. These 15 patients were
      compared to the remaining 41 patients without dysphagia. Using data obtained from
      chart review and interviews with speech pathologists, several factors that
      contributed to dysphagia were found. These included: bite reflexes, slowness of
      oral intake, poor trunk control, inability to feed independently, anticonvulsant
      medication, coughing with meals, choking, and pneumonia. We also noted trends in
      the following factors: presence of tongue thrusting, presence of drooling,
      severity of CP, poor head control, severity of mental retardation, seizures, and
      speech disorders. Factors not related to the presence of dysphagia include:
      subject age, cause of CP, and type of CP. Early, aggressive work-up and
      identification in CP patients with the risk factors outlined above can reduce the
      associated pulmonary complications.

PMID- 1399306
TI  - Pediatric laryngobronchoscopy. 1332 procedures stored in a data base.
AB  - Laryngobronchoscopy (LBS), using both rigid and flexible bronchoscopes, has
      become a frequently performed operation in children. A data base was established
      to enable retrospective evaluation of a large number of LBSs carried out in a
      pediatric center. Experience with 1332 cases of LBS involving 808 patients over
      an 8-year period is presented. The main indications for LBS were inspiratory
      stridor, atelectasis, and suspected foreign body aspiration. Most frequent
      diagnoses at LBS were bronchopneumonia, intubation trauma, tracheomalacia,
      laryngomalacia, and foreign body aspiration. Only 25 complications occurred
      (1.9%) including two cases of xylometazoline intoxication.

PMID- 1399308
TI  - Long-term results of surgery for childhood cholesteatoma.
AB  - The study includes 54 cholesteatomatous ears in 50 children aged 16 years or
      less. The mean follow-up period after surgery was 7.1 years. In 26% of the ears
      the cholesteatoma was 'huge' involving the middle ear and the attic and filling
      the entire mastoid air cell system. A patient had lateral sinus thrombophlebitis.
      Patients with large cholesteatomas underwent canal wall down mastoidectomy with
      simultaneous tympanoplasty and, in most cases, cavity obliteration. Limited
      cholesteatomas were removed using either intact canal wall mastoidectomy or
      tympanotomy approach. Recurrence rate (including both residual and recurrent
      cholesteatomas) for the total series was 15% and 12% for the 50 cases undergoing
      one-stage surgery. Serviceable hearing (< or = 30 dB) was achieved in 57% of the
      ears. A reoperation was necessary in 26% and a third operation in 2%. At last
      follow-up examination, 94% of the ears had intact tympanic membranes but 4
      patients (8%) suffered from cavity-related problems. Possible reasons for the
      disappointing results of surgical treatment for childhood cholesteatoma are
      discussed.

PMID- 1399307
TI  - Urgent adenotonsillectomy for upper airway obstruction.
AB  - Adenotonsillar hypertrophy has been documented to cause chronic upper airway
      obstruction resulting in cardiopulmonary sequelae in children. It has been less
      recognized that long-term adenotonsillar hypertrophy may additionally cause
      acute, life-threatening airway obstruction. A review of 5000 adenotonsillectomies
      performed at 3 New York Medical College affiliated hospitals from 1982 to 1989
      showed 6 pediatric patients with progressive upper airway obstruction severe
      enough to necessitate intubation in the emergency room or operating room, and
      subsequent urgent adenotonsillectomy after cardiorespiratory stabilization.
      Patients were monitored in the ICU with pre- and postoperative blood gases.
      Observations of cyanosis, cor pulmonale, and use of accessory respiratory muscles
      were carefully recorded. This study illustrates that life-threatening upper
      airway obstruction may be due to chronic adenotonsillar enlargement and require
      treatment by urgent adenotonsillectomy.

PMID- 1399309
TI  - Results of surgical treatment for chronic noncholesteatomatous otitis media in
      the pediatric population.
AB  - The long-term results of surgery for chronic otitis media without cholesteatoma
      were analyzed in 76 ears of children aged 16 years or less. The mean follow-up
      period was 6.0 years. Thirty-four ears were subjected to mastoid surgery for
      chronic otorrhea; at final follow-up examination the disease was found to be
      cured in all but one patient. Forty-two patients with sequelae to chronic otitis
      media underwent tympanoplasty without mastoidectomy which was successful in 38
      (91%) of these. At follow-up, 84% of the patients had hearing levels of 20 dB or
      better. Outcome of surgery and hearing results in children were as good as or
      even better than those obtained in adult patients. Complications of surgery were
      rare.

PMID- 1399310
TI  - Central nervous system complications secondary to oto-rhinologic infections. An
      analysis of 39 pediatric cases.
AB  - Fifty-eight central nervous system complications were noted in 39 pediatric
      patients with a primary oto-rhinological infection. The ages ranged from 1 to 15
      years. Eleven patients (25%) had more than one complication. 12.8% of the cases
      died. Leptomeningitis was the most common intracranial complication (54%) Lateral
      sinus thrombosis (LST) occurring in 10 patients (26%) was accompanied with other
      intracranial abnormalities in 80% of cases. Brain abscess as an initial or
      concomitant complication was associated with the highest mortality rates (40%).
      In two of these fatal cases multiple brain abscesses were detected. The low
      incidence of intracranial infections secondary to oto-rhinologic infections and
      the masking effect of antibiotics present difficulties in the early recognition
      of the CNS complication. Despite the value of the modern imaging techniques in
      the investigation of the CNS complication, the clinical oto-rhinologic
      examination is of paramount importance in detecting the original infection in the
      pneumatic spaces of the upper respiratory tract. Additionally, bone scans were
      found of value in demonstrating the osteitic process of these cases.

PMID- 1399312
TI  - Tissue-integrated implants in children.
AB  - The aim of this study is to present our clinical experience with tissue
      integrated extra-oral implants in children. Thirty consecutive cases of children
      with a total of 59 standard titanium fixtures inserted in the temporal bones and
      used as bone-anchorage for auricular epistheses (14 cases) and hearing aids (16
      cases) were studied. The surgical procedure is performed in two steps and
      involves an extremely gentle handling of the soft tissue and bone. The patients
      were followed with regular check-ups for an average of 40 months after hearing
      aid/prosthesis fitting. The fixture survival rate was 96.6% for the whole group.
      The hearing aids had a reaction-free skin penetration in 91.67% of the
      postoperative observations and the prostheses had a reaction-free skin
      penetration in 75.00% of the postoperative observations. It is concluded that the
      use of 'osseointegrated', implants in carefully selected cases, in children,
      appears to be a reliable method for bone anchorage of epistheses and bone
      conduction hearing aids. A close follow-up and control of this patient category
      is especially important with respect to the long-term results.

PMID- 1399311
TI  - Long-term results of Goode's tympanostomy tubes in children.
AB  - The results of a retrospective study of the complications of middle ear
      ventilation by Goode's T-tubes in children are presented. 248 T-tubes were
      inserted into 119 patients. 16.9% progressed to spontaneous extrusion with a mean
      period of ventilation approaching 20 months. 54.9% of patients experienced
      otorrhoea which was found to be significantly more common in those ears with a
      mucoid effusion at the time of T-tube insertion. 21.1% of ears developed a
      persistent perforation where spontaneous extrusion had occurred or the T-tubes
      had been removed. Perforation also occurred more frequently in those with
      otorrhoea.

PMID- 1399313
TI  - Otolaryngology and infectious disease team approach for outpatient management of
      serious pediatric infections requiring parenteral antibiotic therapy.
AB  - Children with community-acquired serious otolaryngologic infections are
      conventionally hospitalized for parenteral antibiotic therapy. However, effective
      and safe outpatient therapy is desirable since it is less traumatic and less
      costly. During a 24-month period outpatient parenteral antibiotic therapy,
      usually once daily i.m. ceftriaxone, was evaluated in 41 children with serious
      otolaryngologic infections (acute mastoiditis, complicated otitis media, severe
      external otitis and severe sinusitis with orbital or periorbital involvement).
      Daily visits and compliant capable parents were considered essential for
      outpatient management. Diagnosis, plan for management and daily follow-up
      evaluations were carried out in cooperation by otolaryngology and infectious
      disease specialists. Nineteen children (45%) were treated initially in the
      hospital and 22 children (55%) were treated entirely as outpatients. The mean
      duration of outpatient treatment, using once daily i.m. ceftriaxone was 5.7 days
      (range 1-13). The overall clinical cure rate was 98% and no serious side effects
      were observed. One case of sinusitis-orbital cellulitis relapsed during therapy.
      Most patients and parents returned to normal life activities within 72 h from
      starting outpatient therapy. Our data suggest that many children with serious
      otolaryngologic infections can be managed successfully and safely as outpatients
      by a combined team of otolaryngology and infectious disease specialists.

PMID- 1399314
TI  - The management of neonatal rhinitis.
AB  - Life-threatening upper airway obstruction secondary to neonatal rhinitis is a
      rare and poorly understood condition. Despite potential lethal effects, there has
      been no basic scientific research investigating the nature of this curious
      condition. This paper retrospectively reviews 8 patients suffering from neonatal
      rhinitis. Both the medical and surgical management of neonatal rhinitis and
      possible aetiological factors involved are discussed. Increasing clinical
      awareness of this condition may, therefore, serve as inspiration for future
      research of both an epidemiological and basic scientific nature.

PMID- 1399315
TI  - Teratoma of the tongue: a case report and review of the literature.
AB  - Teratoma of the tongue is a rare tumor of the oral cavity with only six reported
      cases in the literature. Teratomas are composed of ectoderm, mesoderm and
      endoderm with differentiation to identifiable tissues and organs.
      Embryologically, they are thought to occur as a result of displacement of cells
      from normal tissue during fetal life. In the tongue, the teratoma may result from
      misplaced cells from the tuberculum impar. Differential diagnosis of tongue
      lesions includes thyroglossal duct cyst, lingual thyroid, lymphangioma,
      hemangioma, dermoid cyst, granular cell myoblastoma and heterotopic gastric
      mucosal cyst. Computerized tomography is useful in differential diagnosis and
      defining extent of disease. Surgical excision with laser is curative and
      recurrence is rare.

PMID- 1399316
TI  - Endodermal sinus (yolk sac) tumor of the parotid gland: a case report.
AB  - Malignant salivary gland neoplasms in children are rare, most common being
      mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma and
      adenocarcinoma. Most germ-cell neoplasms of head and neck in children are
      teratomas. The authors report a case of endodermal sinus tumor (EST) of the
      parotid gland in a 2-year-old girl, which recurred after chemotherapy. The role
      of alpha-fetoprotein (AFP) serum level as a helpful marker in differential
      diagnosis and in evaluating tumor progression is underlined.

PMID- 1399317
TI  - Adenosine and carnitine derivatives and calcium movements in rat heart
      sarcoplasmic reticulum.
AB  - Many researches indicate that some Ca antagonists modulate Ca fluxes not only at
      the level of the cytoplasmic membrane but also across the sarcoplasmic reticulum.
      The present study investigates whether certain compounds like propionylcarnitine
      or acetylcarnitine which have the capacity to influence cardiac activity might
      interfere with intracellular Ca movements. The results demonstrate that
      acetylcarnitine and propionylcarnitine do not affect the calcium intracellular
      movement in sarcoplasmic reticulum.

PMID- 1399318
TI  - In-vitro immune response of splenic lymphocytes to portal serum agents from rats
      undergoing hepatic regeneration or hepatic carcinogenesis.
AB  - To clarify the physiologic response of splenic lymphocytes to liver damage and
      the role of this response in regeneration versus malignant transformation, we
      cultured rat spleen lymphocytes with portal sera from rats subjected either to
      partial (70%) hepatectomy or to long-term oral administration of the hepatic
      carcinogen 3'-methyl-4-dimethylaminoazobenzene. Sera taken within 24h after
      partial hepatectomy contained a previously described signal protein which serves
      as a marker of liver damage. The MW 5,000-10,000 serum fraction also contained a
      factor that promoted cell growth, DNA synthesis, glucose utilization, and the
      production of anti-sheep erythrocyte plaque-forming cells in cultures of rat
      splenic lymphocytes. In contrast, the sera of rats subjected to liver damage by
      the carcinogen had no more effect on the cultured lymphocytes than sera from sham
      operated or untreated controls. The signal protein was present initially in
      portal sera from carcinogen-treated rats, but decreased as hepatitis gave way to
      cirrhosis. Subsequent malignant transformation was marked by the appearance of
      serum alpha-fetoprotein. Our results suggest that activation of splenic
      lymphocytes by serum factor(s) is involved in hepatic regeneration and that this
      process is deranged in carcinogenesis.

PMID- 1399319
TI  - Eel calcitonin induces creatine kinase BB activity in the rat kidney medulla.
AB  - We have studied the effect of intravenous injection of eel calcitonin (ECT) on
      creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats.
      CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel
      calcitonin increased CKBB immunoreactivity in the renal medulla in a dose
      dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The
      distribution of activated CKBB in the kidney occurs in the same areas where
      highly specific CT-binding sites have been previously demonstrated, and is in
      agreement with the current concepts on renal actions of this hormone.

PMID- 1399320
TI  - Somatosensory and autonomic deficiencies following trauma in man; evaluation of
      symptomatology by studying peripheral neural correlates and induced tissue
      reactions.
AB  - Careful clinical and experimental studies in well-diagnosed groups of selected
      patients can give valuable information concerning unknown mechanisms involved in
      certain disease states. In particular, microneurographic techniques can be
      applied to assess the underlying neural pathophysiology. It is anticipated that
      future studies performed along these guidelines will contribute to an improved
      diagnosis and/or therapy in a number of clinical conditions.

PMID- 1399321
TI  - Biochemical approach to new medications.
AB  - In this plenary symposium address, the author describes historically his progress
      from the antimetabolite 2,6-diaminopurine to 6-mercaptopurine as a useful drug
      against tumours and leukaemia. Subsequently a 6-mercaptopurine derivative, and
      eventually azathioprine, were discovered to be useful drugs to ensure kidney
      transplant acceptance. Several of his group's diaminopurines proved to be
      selective antifolates in combatting pathogenic bacteria when combined with
      sulfanilamide, a useful drug combination already estimated to have saved a
      million lives.

PMID- 1399323
TI  - Reduction of inflammation by decreasing production of interleukin-1 or by
      specific receptor antagonism.
AB  - Interleukin-1 (IL-1) is a 17-kDa pro-inflammatory cytokine synthesized from a
      variety of cell types primarily in association with disease states or during host
      perturbation such as immune responses. At pM or even fM concentrations, IL-1
      triggers various responses in nearly all cells. It appears that there is little
      or no major role for IL-1 in homoeostatic mechanisms. There are two IL-1's (alpha
      and beta) each with its distinct sequence; there are two IL-1 receptors. Disease
      states such as local and systemic infection, septic shock, degenerative arthritis
      and autoimmune diseases such as nephritis, vasculitis and inflammatory bowel
      disease appear to be mediated, in part, by IL-1. Organ failure, capillary leak
      and death occur in animals after a combination of tumour necrosis factor (TNF)
      and IL-1 which is more effective in inducing these changes than either cytokine
      alone. IL-1 is also a potent inducer of endothelial cell adhesion molecules, IL
      6, and IL-8, a neutrophil chemotactic and activating factor. Strategies for
      reducing the effects of IL-1 have been based on suppression of transcription,
      translation, or secretion; more recently, receptor blockade has been a new
      approach. A naturally occurring IL-1-specific receptor antagonist (IL-1ra), which
      shares 40% conserved amino-acid homology with IL-1 beta, binds to IL-1 surface
      receptors with the same affinity as IL-1 but does not possess agonist activity
      and acts as a competitive inhibitor of IL-1. Studies using the IL-1ra to block
      endogenous IL-1 in a variety of animal disease models suggest that IL-1 plays a
      key role in triggering the cascade of inflammatory responses. In addition, the IL
      1ra reduces the spontaneous production of growth factors and proliferation of
      leukaemic cells. The IL-1ra may be an advantageous therapy in patients with
      sepsis, diabetes, inflammatory bowel, arthritis and cancer.

PMID- 1399322
TI  - The role of chemical mediators released by the endothelium in the control of the
      cardiovascular system.
AB  - The vascular endothelium is much more than just a lining for blood vessels. It
      inactivates many mediators and produces a host of active substances. The
      production of these substances is modulated by interactions between the
      endothelial cells and white blood cells, platelets or constituents of plasma. The
      endothelial cells can be activated by amines, peptides, proteins, nucleotides,
      arachidonic acid and its metabolites, as well as by physical changes such as
      pulse pressure. This activation of endothelial cells is often mediated by
      specific receptors which respond in a variety of ways including the generation of
      prostacyclin and endothelium-derived relaxing factor (EDRF). Both of these
      mediators inhibit platelet aggregation and cause vascular dilatation,
      prostacyclin through increasing cyclic AMP, and EDRF through increasing cyclic
      GMP. EDRF has been identified as nitric oxide (NO) derived from the guanidino
      group of L-arginine. Inhibitors of NO formation cause a strong increase in blood
      pressure, showing that under normal conditions there is a constant formation of
      NO to dilate the vasculature. Endothelin is another agent made by endothelial
      cells; characterized and synthesized in 1988, it is the most potent
      vasoconstrictor so far discovered. Three endothelin isomers have been identified;
      paradoxically, ET-1 strongly releases both prostacyclin and NO, thus modulating
      its own vasoconstrictor activities.

PMID- 1399324
TI  - Inflammatory joint disease: clinical spectra and assessment.

PMID- 1399325
TI  - The intensive care unit. The unfolding ambiguities of survival therapy.
AB  - The intensive care unit (ICU), one of the great achievements of modern medicine,
      is both a set of technologies and a space with a special function. This essay
      traces the evolution of the ICU's crucial technologies, and how the space bearing
      this name was carved out in the hospital. Ethical, legal, and social
      developments, an important part of this story, are incorporated in it.

PMID- 1399326
TI  - Epidemiology of intensive care.
AB  - It is difficult to study the epidemiology of ICUs, as they lack a uniform
      nomenclature and/or classification. The organization and distribution of
      intensive care medicine depend on the size and function of the hospital. The
      patients in ICUs are predominantly men, with a high proportion of elderly
      patients (greater than or equal to 70 years) constituting 25-30% of the total.
      Case-mix, severity of illness and outcome differ from one unit to another, and
      can be compared only if the patients are classified with a common classification
      system. Most survivors of intensive care seem to return to normal or near normal
      functional level within one year. Compared to Western Europe, the United States
      has more ICU beds and a nearly ten times higher admission rate to intensive care.
      These variations can be seen as a result of a fundamental difference in the
      attitudes toward withdrawing or withholding life support.

PMID- 1399328
TI  - Problems in assessing the technology of critical care medicine.
AB  - Technology assessment is becoming increasingly important in the area of critical
      care due both to the explosion of technology associated with this discipline and
      to the realization that future demand for these health care resources will
      undoubtedly exceed the ability to pay. Technology assessment remains both
      confusing and controversial to many physicians. This review tries to address some
      of the confusion by reviewing the basic strategies involved in this process. From
      there, problems and prospects for the evaluation of critical care as a program
      are presented, followed by the assessment of components within the area of
      critical care. Finally, recommendations are made on how technology assessment
      could proceed in the future to best achieve the efficient provision of this
      service.

PMID- 1399327
TI  - An ethical assessment of intensive care.
AB  - Any evaluation of intensive care must include an ethical assessment of that
      technology. This allows us to consider the use of technology in light of the ends
      that we desire. The most pressing ethical issues in intensive care are: forgoing
      life-sustaining treatment, dehumanization of patients and staff within the
      technological environment, and the allocation of the technology that is integral
      to intensive care.

PMID- 1399329
TI  - Critically examining intensive care.
AB  - The economic recession of the last decade brought intensive care systems under
      the light of cost-effectiveness analysis, making use of several instruments
      available in medical practice, and others adapted from for-profit enterprises.
      The present concept of intensive care, particularly its functional and
      organizational interactions with traditional specialties, is at the brink of an
      important revaluation. Studies of the cost-effectiveness of therapeutic actions
      may be grossly biased if they do not consider the complete process of care
      (before, during, and after treatment), analyzing even its smallest elements.

PMID- 1399330
TI  - Neonatal intensive care. When and where is it justified?
AB  - There is a wide panorama of disorders in the newborn infant where neonatal
      intensive care has been proven effective in reducing mortality. Although modern
      neonatal intensive care can be very costly, short and simple interventions for
      support and resuscitation still can be highly beneficial. In reviewing the field
      of neonatal intensive care during the 1980s, it becomes evident that a major
      challenge for the future will be to apply physiological principles of great and
      proven value for the newborn baby to more simple devices. Only thereby can the
      technology of neonatal care defined as a complex of actions-not only equipment
      and techniques-become justified for future generations.

PMID- 1399331
TI  - Inborn errors of amino acid metabolism. The best strategy for their diagnosis.
AB  - We performed a cost-effectiveness analysis to evaluate whether a pediatrician who
      suspects an inherited disease of amino acid metabolism should refer the child to
      a specialist in inborn errors of amino acid metabolism or should prescribe the
      usual screening test, chromatography of amino acids. Actual hospital costs were
      used to value the referral, the tests, and the complications that occur when the
      diagnosis is not recognized. The percent of confirmed diagnoses was chosen as a
      measure of effectiveness. We conclude that it is more cost-effective for a
      pediatrician to refer the child to a specialist, that the best strategy in the
      absence of a referral is to prescribe thin-layer chromatography, and that the
      least cost-effective strategy is to perform ion-exchange chromatography
      immediately.

PMID- 1399332
TI  - Quality assessment of medical research and education.
AB  - Different aspects of the process of evaluating research and education are
      discussed, using the discipline of medicine as a model. The focus is primarily on
      potential problems in the design of an evaluation. The most important aspects of
      an assessment are: to create confidence in the evaluation among scientists and/or
      teachers who are being assessed before beginning; to find experts for whom the
      scientists and/or teachers have professional respect; to choose assessment
      methods in relation to the focus, level, and objectives of the evaluation; and to
      make the report of the evaluation's findings short and explicit.

PMID- 1399333
TI  - Volume and outcome of organ transplantation.
AB  - In general, technically demanding medical procedures are associated with better
      outcomes when they are carried out in institutions and by physicians with higher
      volumes of practice. This paper examines the evidence for a volume-outcome
      relationship in the case of organ transplantation. Although few studies have been
      done on this subject, existing evidence is consistent with improved outcomes at
      higher volumes. Therefore, evidence supports policies that regionalize
      transplantation services.

PMID- 1399334
TI  - Economic evaluation of hypertension treatment.
AB  - A computer simulation model shows that the cost-effectiveness of treating
      hypertension is highly sensitive to different assumptions about the effectiveness
      of treatment, the outcome measure, the cost concept, the discounting of effects,
      and the duration of therapy. Cost-effectiveness analysis should be supplemented
      by another approach--cost-benefit analysis based on the contingent valuation (CV)
      method (the measurement, by survey, of willingness to pay). The CV method is
      tested in two empirical applications that indicate that it is possible to use the
      method in this area. Its results should be interpreted with caution, however,
      since the reliability and validity of the method is not yet established.

PMID- 1399335
TI  - The use of risk-adjusted complication rates to compare hospitals performing
      coronary artery bypass surgery or angioplasty.
AB  - A hospital's quality of care is generally assessed by a review of individual
      records. This study used unadjusted and risk-adjusted complication rates to
      measure the quality of care for hospitals that perform coronary artery bypass
      surgery or angioplasty. Hospitals differed greatly in their complication rates.
      Only a small percentage of this difference was due to differences in the risks
      that patients faced.

PMID- 1399337
TI  - Cochlear implants.

PMID- 1399336
TI  - A methodology for simulating the impact of DNA-probe services on the outcomes of
      pregnancies.
AB  - For certain single-gene disorders, DNA probes allow individuals to make more
      informed decisions about family size and the outcomes of pregnancies. They may
      also have important psychological effects. We present a method of assessing their
      impact on the outcomes of pregnancy. We conclude that the traditional approach,
      which focuses solely on the potential of prenatal diagnostic services to reduce
      affected births, is limited. It neglects the potential of such services to
      promote an increase in unaffected births by reducing the number of unnecessary
      terminations.

PMID- 1399339
TI  - Gallstone therapies.

PMID- 1399338
TI  - CT scanning.

PMID- 1399340
TI  - Extremely preterm infants.

PMID- 1399341
TI  - Complications associated with local and general ophthalmic anesthesia.

PMID- 1399342
TI  - Complications of ocular surgery.

PMID- 1399343
TI  - Complications of glaucoma filtration surgery.

PMID- 1399345
TI  - Complications of surgery associated with ocular trauma.

PMID- 1399344
TI  - Complications of cataract surgery.

PMID- 1399347
TI  - Complications of enucleation and evisceration: prevention and treatment.

PMID- 1399346
TI  - Complications of laser surgery.

PMID- 1399348
TI  - Complications of local ocular anesthesia.

PMID- 1399349
TI  - Complications of pediatric ophthalmic surgery.

PMID- 1399350
TI  - Complications of conjunctival surgery.

PMID- 1399351
TI  - Complications of lacrimal surgery.

PMID- 1399352
TI  - Complications of upper and lower blepharoplasty.

PMID- 1399353
TI  - Complications of corneal surgery.

PMID- 1399354
TI  - Complications of corneal refractive surgery.

PMID- 1399355
TI  - Over-tube is preferable to free-hand technique to avoid recurrence of varices
      after endoscopic injection sclerotherapy. Prospective randomized trial.
AB  - One hundred and two patients undergoing sclerotherapy of esophageal varices,
      using 5% ethanolamine oleate, were randomly allocated to either the over-tube (O
      T) or the free-hand (F-H) group, and 100 patients could be followed at monthly
      intervals for a period of 30.8 +/- 14.7 months (mean +/- SD) after the varices
      had been eradicated. Endoscopy performed one month after the final session of
      sclerotherapy revealed circumferential ulcers and scarring in the lower esophagus
      in 42 of 50 patients (84%) in the O-T group and in 16 of 50 patients (32%) of the
      F-H group, the difference being statistically significant (P less than 0.01). In
      the remaining 8 and 34 patients in the O-T and the F-H groups, respectively, a
      partly fibrotic residual mucosa was seen. There was a recurrence of the varices
      in the residual mucosa in 14 (28%) in the F-H group during the mean follow-up
      period of 25.6 months, while there were five patients (10%) with a recurrence of
      varices in the O-T group, the difference being statistically significant (P less
      than 0.05). The survival rates showed no statistical significance. Two patients
      in the F-H group had recurrent bleeding. We conclude that the over-tube technique
      of sclerosing esophageal varices reduces the rate of recurrence of the varices,
      in the long term follow-up, and after formation of a circumferential scarring in
      the lower esophagus.

PMID- 1399356
TI  - Transmediastinal esophagectomy and colon interposition without thoracotomy.
AB  - In the Central Hospital of Central Finland (responsibility for 250,000
      inhabitants) the technique of transmediastinal esophagectomy and colon
      interposition without thoracotomy was used on 19 consecutive patients in the
      years 1983-1988. Fourteen of the patients had a malignant and five a benign
      disease. The type of cancer was squamous cell cancer in 13, and adenocancer in 1
      case. All five patients with a benign disease had an etiology of corrosion by
      various agents. Two of them had a spontaneous rupture. In three cases the
      perforation occurred as a complication of endoscopic dilatation. There were no
      peroperative but one postoperative death. Six minor complications were well under
      control. The survival rate of cancer patients is comparable with the results
      reported by other authors. All five patients with a benign disease are in
      excellent condition with a follow up time from 4 to 100 months (mean 44 mo).

PMID- 1399357
TI  - Gastrectomy for advanced gastric carcinoma with invasion to the serosa.
AB  - A review of gastrectomy for 332 patients who had advanced gastric cancer with
      serosal exposed (S2) or adjacent organs invaded (S3) was made. Simple gastrectomy
      (SG) was carried out in 144 patients while radical gastrectomy (RG), which
      consisted of systemic lymphadenectomy in addition to SG, was used for the other
      188 patients. The type of gastrectomy was chosen arbitrarily by the surgeons
      except that SG was usually selected when some non-curable factors were present.
      The operative mortality of SG was 2.7% and that of RG was 3.2%. More lymphnodes
      could be obtained by RG. Of the 152 patients with S2 who received RG, 46.7% of
      metastatic lymphnodes could not be identified by SG, while of the 36 patients
      with S3, 75% of metastatic nodes would be misjudged if SG was carried out. The 5
      year-survival rate of RG for stage 3 patients was 42.4% and that for stage 4
      patients was 28.2%. Better postoperative long-term-survival was achieved by RG
      than SG in both stage 3 and 4 patients. When considering the curability of the
      gastrectomy, the best outcome in stage 3 patients was found in those who
      underwent an absolute curative resection. Of the stage 4 patients those who
      received an absolute non-curative resection had the worst result. We recommend
      that RG be the procedure of choice in treatment of serosal gastric cancer in the
      absence of non-curable factors. Other adjuvant therapies may be considered after
      an absolute non-curative gastrectomy in stage 4 serosal cancer patients when
      multiple non-curable factors were present.

PMID- 1399358
TI  - Laparoscopic cholecystectomy in India.
AB  - The first 100 cases of laparoscopic cholecystectomy carried out in a "developing
      country" are studied. There were 77 females and 23 males. The mean age was 48
      years (24-82 years). There was no mortality and 2% morbidity. The mean operative
      time was two hours and 15 minutes in the first 50 cases, one hour and 50 minutes
      in the subsequent 50. Twelve cases were converted to open surgery, nine within
      the first 50 cases, three in the subsequent 50. In developing countries the
      challenge of financial constraints as also a different spectrum of abdominal
      pathology calls for greater efforts of innovation and improvization. However, the
      rewards of laparoscopic cholecystectomy as compared to open cholecystectomy are
      significant in developing countries in terms of shorter hospitalisation (3.6 vs.
      13 days), early return to work (12 vs. 36 days), better hospital bed utilization,
      and reduced expense.

PMID- 1399359
TI  - Hepatic fascioliasis and biliary surgery.
AB  - This series represents seven cases of hepatic fascioliasis (HF), two diagnosed as
      the sequelae of the disease and five showing the parasite itself at the time of
      the primary surgical intervention. The mean history of the symptoms was 42.6
      mths. All of the patients were initially misdiagnosed as having cholecysto-
      and/or coledocho-lithiasis or hepatitis. Definite diagnosis was established
      intraoperatively in each instant. At surgery cholecystectomy, choledochotomy with
      extirpation of the flukes from the biliary tree and T-tube biliary drainage was
      performed without any complications in five patients. The remaining two patients
      were suffering from recurrent cholangitic episodes and were regarded as sequelae
      and therefore treated with hepatic peri-arterial neurectomy with favourable
      results. Six patients received medical treatment involving emetine hydrochloride.
      Two patients failed to return for follow-up while others were seen to be well 6,
      12, 24 mths and 13 and 24 yrs postoperatively, implying promising long-term
      results both in the active and chronic stages of HF.

PMID- 1399360
TI  - Colostomy complications in infants and children.
AB  - Seventy-seven colostomies were performed in 74 patients: 35 for high anorectal
      agenesis, 34 for Hirschsprung's disease, 2 for necrotizing enterocolitis, 2 for
      small left colon syndrome, and 1 for volvulus neonatorum with perforation. There
      were 55 boys and 19 girls with a mean age of 0.8 years. The different types of
      colostomies performed were: transverse loop in 48, sigmoid loop in 21, transverse
      end in 4, descending end in 2, sigmoid end in 1, and transverse double barrel in
      1. Forty-seven patients developed stomal complications (74.6%). Eleven patients
      died, but only in 2 (2.7%) were the deaths directly related to colostomy
      formation. Five patients required stomal revision (6.8%). The incidence of
      complications was neither related to the age nor to the primary indication for
      the colostomy, but sigmoid colostomy was associated with a lower complication
      rate compared to transverse colostomy (52% versus 81% 0.02 greater than p greater
      than 0.01). A sigmoid loop colostomy should be used whenever possible.

PMID- 1399361
TI  - Immediate return to unrestricted work after inguinal herniorrhaphy. Personal
      experiences with 27,267 cases, local anesthesia, and mesh.
AB  - Complete safety of the patient and unblemished success without recurrence or
      complication may be assured after inguinal herniorrhaphy as an out-patient if
      uncompromising intimate attention is paid to the surgical technique in which
      local anesthesia, polyvinyl ester mesh, and rectus abdominis tendon transfer are
      used instead of coaptive techniques, and if the post-operative regimen of
      immediate post-operative ambulation and unrestricted activity is employed. Return
      to work requiring heavy lifting the same day reduces tension on the mesh,
      increases the strength of the incision, prevents complications and minimizes
      pain. The surgical procedure and the virtues of the regimen, which has been
      eminently successful in 27,267 personal cases, with mesh employed in 18,214
      patients, are described.

PMID- 1399362
TI  - Inguinal hernia repair in infants less than six months of age.
AB  - Previous studies reviewing the morbidity and mortality of infant inguinal hernia
      surgery have all been done in university hospital settings. From our community
      based tertiary hospital, 100 consecutive cases on infants less than six months of
      age, undergoing inguinal hernia repair, were reviewed. No infants were excluded.
      Sixty-eight were full term and 32 were premature. A number of different variables
      were analyzed and none appeared to affect outcome. Infants were followed for
      three to five years. There were no true complications in any infant in this
      series, although six infants developed wound erythema that resolved
      spontaneously. Parents were given a questionnaire to subjectively evaluate the
      infant before and after surgery with 78% showing improvement.

PMID- 1399363
TI  - Metastatic lung tumors and extended indications for surgery.
AB  - From 1973 to 1989, 110 thoracotomies for metastatic lung tumors were done on 85
      patients, in our institution. The overall actuarial five-year survival rate was
      31%. The five-year survival rate for carcinoma was 40% and for sarcoma was 11%
      (less than 0.05). A favorable outcome was obtained in the group with primary
      tumors of the breast, head-neck, and chorion. The outcome for patients with bone
      and soft tissue tumors was poor. The significant predictors of a better long-term
      survival for metastatic lung tumors were disease-free interval (DFI) greater than
      12 months, tumor size less than or equal to 30 mm in diameter, and tumor doubling
      time (TDT) greater than 40 days (p less than 0.05). The number of nodules and the
      laterality of the sites of recurrence did not relate to survival time. Of 22
      patients undergoing regional lymph node dissection, seven (32%) had positive
      nodes. Even in cases of a recurrent pulmonary metastasis, the three-year survival
      in those with multiple thoracotomies was 16%. We wish to draw attention to the
      finding that a prolonged survival time can be achieved for patients undergoing
      regional lymph node dissection or even repeated resections for a recurrent
      pulmonary metastases.

PMID- 1399364
TI  - Does total thyroidectomy induce metabolic bone disturbance?
AB  - Bone mineral content of 38 thyroidectomized patients with well differentiated
      thyroid carcinoma were determined. Seventeen patients were totally
      thyroidectomized and 21 patients were non-totally thyroidectomized (lobectomy).
      Thirty-eight healthy males and females were served as age-matched controls.
      Trabecular bone mineral content of lumbar vertebra was evaluated by quantitative
      CT method. Bone metabolic parameters in serum were measured. No significant
      differences were observed in the mean bone mineral content and BMC-index of
      totally thyroidectomized patients compared with non-totally thyroidectomized
      patients and control. Serum calcitonin level was not reduced in totally
      thyroidectomized. It is concluded that after total thyroidectomy, bone metabolic
      disturbance was not significant, and that when calcitonin remained at its basal
      level, it had no effects on bone metabolism.

PMID- 1399366
TI  - The nature of inner cellular lining of the expanded polytetrafluoroethylene
      vascular graft: immunohistochemical study.
AB  - Histological and immunohistochemical studies of the healing processes of expanded
      polytetrafluoroethylene (PTFE) vascular graft were performed. In the animal
      experiment, endothelial cell lining, confirmed by immunohistochemical staining
      for anti-Factor VIII related antigen, existed nearly over all of the pannus. The
      endothelial cells also formed to some extent over the graft without pannus.
      Endothelialization showed a close dependency on the surface condition of the
      underlying tissue rather than on a time factor. In the human experiment, an
      endothelial island was observed in the middle portion of the graft in one case,
      supporting the hypothesis of the blood stream origin of endothelial cells.

PMID- 1399365
TI  - Calcitonin gene-related peptide as a tumor marker for medullary thyroid
      carcinoma.
AB  - We have established a radioimmunoassay method for calcitonin gene-related peptide
      (CGRP) to monitor changes in plasma CGRP levels in patients with medullary
      thyroid carcinoma (MTC). Preoperative plasma CGRP levels (normal level less than
      12.7 pg/ml) were as high as 128 pg/ml to 2,010 pg/ml in all five patients with
      MTC. Ten of 17 postoperative patients with MTC were positive for CGRP. A
      provocation test was performed in 12 patients with MTC. Plasma CGRP changes
      roughly paralleled serum calcitonin levels. In particular, in three patients with
      poorly-differentiated MTC which progressed aggressively, plasma CGRP levels were
      increased to 1.4 to 2.0 times levels before the test, i.e., lower than the 2.8-
      to 23.3-fold increase in nine patients with the well-differentiated MTC. These
      results suggest that CGRP may be a humoral marker of medullary carcinoma and be
      related to degree of malignancy.

PMID- 1399367
TI  - Fecoflowmetry: a new parameter assessing rectal function.
AB  - Fecoflowmetry is a new technique by which the fecal flow rate is studied through
      recorded curves representing the changes which occur in the rate against time.
      Fecal flow rate is the product of rectal detrusor action against outlet
      resistance. The technique was performed on 36 normal volunteers and 8 chronically
      constipated patients. A one liter water enema was given to the individual. On
      feeling the desire to defecate, he or she was placed on the commode of a
      fecoflowmeter and was asked to defecate. Defecation flow curves were obtained.
      Evaluation of the curve comprises reporting on the defecated volume, flow time,
      maximum and mean flow rates and the shape of the curve. The technique was
      developed to stimulate natural defecation. It provides quantitative and
      qualitative data concerning the act of defecation. It assesses all objective
      parameters in one test. The procedure is simple, non-invasive and constitutes a
      useful screening tool in defecation and rectal disorders.

PMID- 1399368
TI  - Primary colonic non-Hodgkin lymphomas: a retrospective clinicopathologic study of
      14 cases.
AB  - Fourteen cases of primary colonic non-Hodgkin lymphomas (NHL) with a mean age of
      51.5 yrs and 64.3% of them female, are reported. While diagnoses were only
      obtained by cytologic or histopathologic means, 35.5% of the cases were in Stage
      1e (S1e) and a further 42.6% in Stage 2e (S2e) and 7.1% in Stage 3e (S3e)
      according to the modified Manchester classification. 63.9% were of immunoblastic
      and 21.3% lymphoblastic type according to the Kiel classification. 85.2% of the
      tumours were located at the caecum. While acute abdomen required surgery in two
      patients, 85.2% of the series underwent radical interventions. 14.2% were able to
      receive chemotherapy with a subsequent total morbidity and mortality figures of
      21.3% each. It is the authors' argument that prognosis is not solely dependent on
      the age, sex or the malignancy state of the tumour but more on its infiltrative
      stage and on the advent of treatment, whether by radical surgery and/or medical
      means.

PMID- 1399369
TI  - Factors affecting postoperative mortality in abdominal trauma.
AB  - Records of 345 patients in whom laparatomies were performed because of blunt and
      penetrating abdominal trauma were reviewed retrospectively with respect to
      factors affecting mortality. One hundred and twenty-eight patients had blunt
      abdominal trauma (Group I), 114 patients had gunshot wounds of the abdomen (Group
      II), and 103 patients had stab wounds of the abdomen (Group III). Mortality rates
      were 14.8%, 12.3% and 1.9% in groups I, II and III respectively. The presence of
      head trauma especially if accompanied by hypotension in group I, and the presence
      of chest trauma (hemothorax and/or pneumothorax) and hypotension (less than 90
      mmHg) in group II were associated with a high mortality rate (p less than 0.05).
      Of the two patients who died in group III, one had septic shock due to massive
      intestinal necrosis and the other had hemorrhagic shock due to multiple organ
      injury and bleeding from an injured internal thoracic artery as the cause of
      death.

PMID- 1399370
TI  - Selective approach to repair of ureteropelvic junction obstruction: results of
      126 pyeloplasties assessed on clinical and radiological bases.
AB  - Record-files of 126 pyeloplasties of different types performed on 119 patients (7
      bilaterally), between 1966 and 1989, have been reviewed in an attempt to
      illustrate the selective approach to hydronephrosis due to ureteropelvic junction
      obstruction. Clinical success was achieved in all cases. A new grading system for
      assessing urographic impairment has been suggested. Radiological success was
      obtained in 123 (97.6%) renal units. The near total success is attributed to the
      theme of selective approach.

PMID- 1399371
TI  - Pelvic lymphadenoscopy. A simple reliable method for the staging of pelvic
      cancers.
AB  - The staging of pelvic cancers using imaging techniques is not very precise, even
      with the most recent methods. However, optimal treatment depends on the results
      of this staging. In our experiment, we carried out a pelvioscopy prior to any
      curative treatment on all our patients who had had pelvic cancer for at least
      three years. Seventy-eight pelvioscopies were performed with 48 patients,
      entailing minimum morbidity and no mortality. For 23 patients, the lymph nodes
      were metastasized even though the C.T. were considered normal. With this simple
      method, staging of pelvic cancers can be improved and this extensive, unnecessary
      surgery can be avoided in many cases.

PMID- 1399372
TI  - Free-hand CT-guided needle for biopsy and drainage of intracerebral lesions. Ten
      years experience.
AB  - A series of 227 needle procedures monitored by serial CT scans was performed by
      free-hand technique on 147 patients at two suburban hospitals over a 10 year
      period. Under local anesthesia, 75 suspected brain tumors were biopsied; 52
      intracerebral hematomas were evacuated, and 28 cerebral abscesses were drained.
      There was one complication of postoperative hemorrhage.

PMID- 1399373
TI  - Evaluation of an intensive care unit in a teaching hospital in Saudi Arabia.
AB  - Intensive Care Units (ICU) in general hospitals have become a standard
      requirement in tertiary care centres. However, the appropriateness of their use
      is not widely known. We have used the Therapeutic Intervention Scoring System
      (TISS) to evaluate a multidisciplinary ICU in a teaching hospital in Saudi
      Arabia. The average occupancy rate was 79%, the nurse: patient ratio was 1:1.4,
      duration of stay 4.1 +/- 3.5 days, and mortality was 1.4%. The distribution of
      severity of illness was as follows: Classes I & II, 82%, and Classes III & IV,
      18%. The average TISS points were: daily per patient 15.1 +/- 2.7 (range 11.5
      21.7), total per day 125.6 +/- 38.2 (range 35-211), and patient points per nurse
      was 21.1. We conclude that, although less than 20% of patients required unique
      ICU services, the use of our ICU was appropriate to the current medical and
      manpower training needs of the community it was designed to serve, but the basis
      of nurses' complaints of overwork remains to be determined.

PMID- 1399374
TI  - Spontaneous pneumoperitoneum without peritonitis.
AB  - Spontaneous pneumoperitoneum without peritonitis is a rare phenomenon which poses
      a dilemma to the surgeon faced with this problem. Two such cases and their
      outcome are presented. The first case was caused by barotrauma during positive
      pressure ventilation and was treated by laparotomy. No perforated viscus was
      found. The second case was caused by tracheal rupture during emergency intubation
      and was treated by observation until complete resolution. Both patients died for
      reasons unrelated to the pneumoperitoneum. The mechanisms for passage of air from
      the chest into the abdominal cavity were through the diaphragm in the first case
      and along the great vessels in the second. A compilation of other etiologies of
      pneumoperitoneum without peritonitis as extracted from the literature is
      presented. In the presence of pneumoperitoneum without peritonitis and when the
      clinical history does not suggest perforation of a viscus, we advise performing
      an abdominal tap. If negative, continued observation is advised.

PMID- 1399375
TI  - Spontaneous intracerebral hemorrhage following carotid endarterectomy. Experience
      of 328 operations from 1983-1988.
AB  - In a consecutive series of 328 carotid endarterectomies there were two cases of
      postoperative intracerebral hemorrhage. The patients with transient ischemic
      attacks and subsequent major cerebral infarction had repair of their very tight
      carotid stenosis. Each developed intracerebral hemorrhage after a symptom free
      interval and hypertension was uncontrolled during the postoperative period.
      Hypertension is a significant complication of carotid endarterectomy and may be a
      prominent factor in the development of intracerebral hemorrhage after carotid
      endarterectomy. Also defective cerebrovascular autoregulation in chronic ischemic
      brain regions may predispose patients to intracerebral hemorrhage.

PMID- 1399376
TI  - Diagnosis and treatment of cortical tumours of the suprarenal gland.
AB  - The authors report on their own groups of benign (20 patients) and malignant (14
      patients) cortical tumours of the suprarenal gland. In both kinds of tumour the
      occurrence is higher in females. Adenoma occurred more often in the left adrenal
      gland and cancer in the right one. Some tumours manifested themselves by an
      increased production of suprarenal hormones, others were hormonally inactive and
      did not become manifest until the later stage of development. In the therapy of
      adenomas the classical lumbar approach through the 11th intercostal space is
      adequate, in the case of cancer and extended lumbotomy laparotomy or thoracotomy
      is necessary. The need of participation of other specialists in the treatment
      (endocrinologist, radiologist, oncologist, anaesthesiologist) is emphasized.

PMID- 1399377
TI  - A comparative trial of aztreonam versus gentamicin in the treatment of urinary
      tract infections.
AB  - A prospective, randomized trial was conducted to compare the efficacy of
      aztreonam, a monobactam antibiotic, and gentamicin in the treatment of serious
      urinary tract infections. Fifty-five patients with a suspected or confirmed
      infection were randomized, 28 received aztreonam and 27 received gentamicin. Both
      antibiotics had a high clinical response rate (aztreonam 92%, gentamicin 85%).
      However, the duration of treatment was significantly shorter (p = 0.037, Wilcoxon
      Rank Sum Test) when aztreonam was used. There were no cases of toxicity with
      either antibiotic but 5 patients who received gentamicin required dose
      alteration. Aztreonam is well tolerated and is no less effective than gentamicin
      in the treatment of urinary tract infections and has advantages in convenience of
      use and duration of treatment.

PMID- 1399380
TI  - The flexible cystoscope.
AB  - We have been using the flexible cystoscope since 1987. Detailed information is
      given concerning the technique of flexible cystoscopy, its indications,
      advantages and disadvantages. A comparison is made with the results obtained
      using the rigid cystoscope in an initial series of 100 patients, yielding false
      negative results in only 8% of cases during the learning period. The flexible
      scope can be successfully employed for Neodymium YAG laser coagulation of
      superficial bladder tumours. The conclusion is reached that once the urologist
      has learned how to use it, he will consider the flexible cystoscope as a
      fundamental tool in his diagnostic armamentarium and false negative results will
      decrease almost to zero, especially if additional investigations, namely
      cytology, are routinely adopted.

PMID- 1399379
TI  - Low ureteral obstruction caused by umbilical ligament in a 37 year old man: a
      case report.
AB  - Arterial vascular anomalies rarely cause extrinsic ureteral obstruction and only
      11 cases have been reported so far. This paper deals with an unusual extrinsic
      obstruction of the left ureter caused by a residue of the umbilical artery in a
      37 years old man. The patient had left flank pain due to serious hydronephrosis
      on the same side. At operation a fibrous cord, a residue of the left umbilical
      artery, partially obstructed the distal left ureter. Partial left terminal
      ureterectomy with ureteroneocystostomy was performed. In the differential
      diagnosis of low extrinsic ureteral obstructions also the uncommon vascular
      anomalies of the umbilical artery should be taken into consideration.

PMID- 1399378
TI  - A double-blind placebo-controlled trial of omeprazole on urinary pH in healthy
      subjects.
AB  - Urinary pH is related to urinary calculus formation as well as urinary infection.
      Omeprazole is an effective inhibitor of gastric acid secretion through inhibition
      of the parietal cell H+K+ATPase. In this study we have evaluated a possible
      effect of omeprazole on urine acidification. Ten healthy male subjects took
      placebo and omeprazole, 40 mg o.m., for 10 days in a double-blind placebo
      controlled trial. Morning fasting urinary pH was measured on day 10 of each
      treatment course using a pH meter. No effect of omeprazole on urinary pH could be
      demonstrated. It is thus unlikely that it is necessary to take omeprazole
      treatment into consideration in stone screening. As omeprazole did not affect
      urinary pH, no urological side effects related to changes in urinary pH can be
      expected.

PMID- 1399381
TI  - Clinical assessment of carcinoma in situ of the human urinary bladder.
AB  - Recent interest in intravesical instillation of bacillus Calmette-Guerin for the
      management of carcinoma in situ (CIS) of the bladder prompted us to review our
      results of total immediate cystourethrectomy. From 1975 to 1987, we surgically
      treated 302 patients with primary bladder tumours. Of these, 21 bladder tumours
      were histologically diagnosed as CIS, and total immediate cystourethrectomy was
      performed in all cases. The lesions were classified into three types: primary CIS
      accompanied by neither previous nor simultaneous tumours of the urinary tract
      (Type 1, 9 patients), concomitant CIS associated with superficial papillary
      tumour (Type 2, 6 patients), and secondary CIS detected during the follow-up
      period after treatment of the superficial papillary tumour (Type 3, 6 patients).
      Primary CIS was more often diagnosed according to subjective symptoms such as
      micturition pain than concomitant CIS. Secondary CIS was diagnosed in all
      patients by routine examinations including cytology and cystoscopy. There was no
      particular relationship between the time of recurrence of the tumour and the
      occurrence of secondary CIS. Within the same period, 60 patients with stage T1
      bladder tumour were treated by total cystourethrectomy. The actuarial 5-year
      survival rate was 77% for T1 and 75% for CIS. The 5-year survival rate was 71%
      for Type 1, 83% for Type 2, and 67% for Type 3 CIS with no difference among the
      CIS types. Tumour invasion to the bladder, prostate, ureter, or lymph nodes was
      observed in 9 (42.9%) of the 21 patients, although cystourethrectomy was
      performed within 3 months of the diagnosis. Examination of ABH antigens did not
      allow prediction of invasion of CIS. Our findings suggest that the invasive
      potential of CIS may seriously limit the indications of conservative treatment
      against carcinoma in situ.

PMID- 1399383
TI  - Superficial bladder cancer treated by total cystectomy: tumour characteristics
      and patient survival.
AB  - Of 113 patients with bladder cancer who underwent total cystectomy from January
      1980 to December 1990, 30 (27%) had superficial tumours (pTa, pTis, and pT1).
      Nineteen of these 30 patients (63%) were primarily treated by total cystectomy
      and the remaining 11 (37%) had a past history of treatment for bladder cancer.
      Major reasons for choice of total cystectomy were multifocal tumours, frequent
      recurrence, and diffuse carcinoma in situ. Histologically stage pT1, grade 3
      tumours were frequently accompanied by carcinoma in situ and often by lymphatic
      invasion. None of the 24 patients undergoing pelvic lymphadenectomy had lymph
      node metastasis. Of 25 male patients 15 (60%) underwent simultaneous prophylactic
      urethrectomy. Two of the remaining 10 males (20%) not undergoing this additional
      operation died of subsequent urethral recurrence. The 5-year actuarial survival
      rate was 80% for the 30 patients when all causes of death were considered. It was
      concluded that patients with superficial bladder cancer who undergo total
      cystectomy without prophylactic urethrectomy require close follow-up with
      urethral washings for cytology to detect early urethral recurrence, an important
      determinant for survival.

PMID- 1399382
TI  - Detection of blood group surface antigens of urinary bladder tumours using
      monoclonal antibodies with the avidin-biotin complex technique.
AB  - We examined 8 normal bladder transitional epithelia and 65 transitional cell
      carcinomas of the urinary bladder of various stages and grades for the presence
      of ABO(H) blood group surface isoantigens using the immunoperoxidase staining via
      the Avidin-Biotin Complex (ABC) methods. It was found that 27% of patients with
      grade I tumours, 50% with grade II tumours and 82% with grade III tumours had
      loss of cell surface isoantigens. When correlated with the clinical stage the
      tumours showed no surface isoantigens in stage D, while 65% of patients with
      stage A tumours were positive for surface antigens. From among 37 patients (57%),
      28 (43%) survived for more than five years. Our results suggest that surface
      antigens of transitional cell carcinoma of the urinary bladder tended to
      disappear as the histologic changes of the tumour progressed. It also was noted
      that a loss of ABH(O) surface isoantigens was a bad prognostic sign.

PMID- 1399384
TI  - Post-herniorrhaphy paravesical granuloma simulating pelvic metastasis in a
      patient with bladder cancer.
AB  - We describe a rare case of bladder cancer associated with paravesical post
      herniorrhaphy foreign body granuloma with abscess formation which simulated a
      lymph node metastasis. Management of this particular case is discussed and the
      literature is reviewed.

PMID- 1399385
TI  - Electrical stimulation of pelvic floor musculature by percutaneous implantable
      electrodes: a case report.
AB  - A forty-year-old man with reflex urinary incontinence due to spinal cord injury
      was treated with electrical stimulation of the pelvic floor musculature. In this
      case we employed percutaneous implantable electrodes and an external pulse
      regulator. After 4 weeks of stimulation incontinence was improved and
      urodynamically maximum cystometric capacity increased from 220 ml to 350 ml. Our
      method is easy and not invasive. This technique can be an alternative for the
      electrical stimulation for urinary incontinence.

PMID- 1399386
TI  - Acute experimental unilateral orchitis in the rabbit and its effect on fertility.
AB  - We examined the nature of contralateral damage following unilateral orchitis to
      see if an immunologically mediated mechanism was present. Experimentally induced
      orchitis in 18 white New Zealand rabbits were examined and compared to 20 in the
      control groups. Serum antisperm antibody presence and bilateral testicular
      biopsies (Johansen biopsy score, mean seminiferous tubule diameter) were examined
      and pregnancy rates were noted. Acute orchitis seemed to be a causative factor in
      production of antisperm antibody and the presence of antisperm antibody caused
      histologic changes in contralateral testicles and therefore impaired fertility.

PMID- 1399387
TI  - Primary chemotherapy in the management of low stage (IIA and IIB) non
      seminomatous germ cell testicular tumours.
AB  - In a prospective study a total of 65 patients in clinical stages IIA and IIB
      nonseminomatous testicular tumours were treated by primary chemotherapy followed
      by retroperitoneal lymphadenectomy in cases with residual disease. The patients
      were given a combination of cisplatin, vinblastine and bleomycin, or also
      etoposide. Sixty-two patients (95.4%) achieved complete response: 39 (60%) by
      chemotherapy alone and 23 (35.4%) following surgical removal of residual disease.
      Three patients died; there were two drug-related deaths during PVB chemotherapy,
      one patient had progression of disease following chemotherapy and died as a
      result of disease dissemination. Three patients relapsed from complete response
      following chemotherapy, two of them died within 19 and 29 months after the onset
      of therapy. The third patient received second-line chemotherapy and gained
      complete response again. Of the 65 patients, 60 (92.3%) survive with no evidence
      of disease. The follow-up period ranged from 6 to 79 months (mean 39.4 months,
      median 39 months).

PMID- 1399388
TI  - Renal tubular epithelial antigen-containing immune complexes stimulate
      interleukin-1 production by monocytes from patients with glomerulonephritis.
AB  - We have investigated the effect of immune complexes (IC) derived from human renal
      tubular epithelial (RTE) antigen on the release of interleukin-1 (IL-1) in
      monocyte cultures from patients with glomerulonephritis (GN). When peripheral
      blood monocytes (PBM) were activated by IC, substantial amounts of IL-1 could be
      detected in the supernatants as measured by mouse thymocyte assay. The IC-induced
      IL-1 activity was significantly higher in patients with GN than in normal
      controls. To avoid the effect of prostaglandins on the IL-1 assay, we cultured
      PBM with addition of indomethacin and assayed IL-1 activity in the culture
      supernatants. This cyclooxygenase inhibitor augmented IC-induced IL-1 production.
      The results suggest that IC are involved in stimulating IL-1 production by PBM
      and thus play a role in the immune response in GN.

PMID- 1399389
TI  - Catheter types and their abdominal implantation in peritoneal dialysis.
AB  - In the period 1976-1990 a total of 282 chronic uraemic patients were put to
      peritoneal dialysis by means of abdominally implanted Tenckhoff catheters, out of
      which 170 had to be replaced. Description of the catheter types is followed by a
      summary of the rules of surgical implantation and postoperative treatment that
      should be observed for the peritoneal dialysis to be effective. Discussed are the
      causes and percentage distribution of changes that call for catheter replacement,
      finally the alternatives of conservative therapy.

PMID- 1399390
TI  - [Arthralgia].

PMID- 1399391
TI  - [Principles of virus diagnosis].

PMID- 1399392
TI  - [Current vaccination strategies].

PMID- 1399393
TI  - [New aspects in diagnosis and therapy of viral hepatitis].

PMID- 1399394
TI  - [18-year-old patient with petechial hemorrhage].

PMID- 1399395
TI  - [Omeprazole].

PMID- 1399396
TI  - [Can a serum calcium deficiency develop in transfusion of larger amounts of
      erythrocyte concentrates and fresh frozen plasma and should it then be
      corrected?].

PMID- 1399397
TI  - [Hemodilution in the therapeutic overall plan in acute cerebral ischemia].

PMID- 1399398
TI  - [Dyslipoproteinemia. Satellite symposium following the 3rd German Physicians'
      Congress. Dresden, 22 May 1992].

PMID- 1399399
TI  - Adhesion molecules involved in the trafficking of normal and malignant
      leukocytes.
AB  - Adhesion molecules involved in leukocyte recruitment and lymphocyte recirculation
      impact on several aspects of tumor biology--the primary host response, the
      delivery of effective adoptive immunotherapy and the hematogenous spread of
      malignant cells. Common to all three processes are receptor-mediated adhesive
      interactions between circulating cells and the vessel wall. Recruitment of
      circulating lymphocytes, monocytes and natural killer cells is essential for an
      effective host response or successful adoptive immunotherapy. Thus poor induction
      or blockade of leukocyte binding sites on the microvasculature of tumor implants
      may help malignancies evade natural defenses. In addition, perturbation of
      adhesion receptor function during ex vivo expansion may alter the behavior of
      infused cells in adoptive immunotherapy protocols. Finally, circulating malignant
      cells may utilize receptors normally involved in recruitment and recirculation.
      This paper reviews the function and regulation of adhesion molecules involved in
      normal leukocyte trafficking. The evidence implicating specific adhesion
      receptors in the spread of lymphoid malignancies through the bloodstream is then
      discussed.

PMID- 1399400
TI  - Expression of heparanase by platelets and circulating cells of the immune system:
      possible involvement in diapedesis and extravasation.
AB  - Interaction of T and B lymphocytes, platelets, granulocytes, macrophages and mast
      cells with the subendothelial extracellular matrix (ECM) is associated with
      degradation of heparan sulfate (HS) by a specific endoglycosidase (heparanase)
      activity. The enzyme is released from intracellular compartments (i.e.,
      lysosomes, specific granules) in response to various activation signals (i.e.,
      thrombin, calcium ionophore, immune complexes, antigens, mitogens), suggesting
      its regulated involvement in inflammation and cellular immunity. In contrast,
      various tumor cells appear to express and secrete heparanase in a constitutive
      manner, in correlation with their metastatic potential. Heparanase enzymes
      produced by different cell types may exhibit different molecular properties and
      substrate cleavage specificities. The platelet enzyme appears also in a latent
      form. It can be activated by tumor cells and thereby facilitate their
      extravasation in the process of metastasis. Degradation of ECM-HS by all cell
      types was facilitated by a proteolytic activity residing in the ECM and/or
      expressed by the invading cells. This proteolytic activity produced a more
      accessible substrate for the heparanase enzymes. Heparanase-inhibiting,
      nonanticoagulant species of heparin markedly reduced the incidence of lung
      metastasis in experimental animals. These species of heparin also significantly
      impaired the traffic of T lymphocytes and suppressed cellular immune reactivity
      and experimental autoimmune diseases. Heparanase activity expressed by intact
      cells (i.e., platelets, mast cells, neutrophils, lymphoma cells) was found to
      release active HS-bound basic fibroblast growth factor from ECM and basement
      membranes. Heparanase may thus elicit an indirect neovascular response in
      processes such as wound repair, inflammation and tumor development. The
      significant anticancerous effect of heparanase-inhibiting molecules may therefore
      be attributed to their potential inhibition of both tumor invasion and
      angiogenesis. Both normal leukocytic cells and metastatic tumor cells can enter
      the bloodstream, travel to distant sites and extravasate to the parenchyma at
      these sites. We suggest that heparanase is utilized for this purpose by both
      types of cells. Other functions (i.e., enzyme activities, adhesive interactions,
      chemotactic and proliferative responses) of metastatic tumor cells seem to mimic
      the equivalent functions of leukocytes as they migrate across blood vessels to
      gain access to sites of inflammation.

PMID- 1399401
TI  - Extravasation of antitumor effector cells.
AB  - Development of effective local immune responses depends on the ability of
      lymphocytes to extravasate and migrate into nonlymphoid solid tissues. Different
      lymphocyte subpopulations seem to vary in their abilities to extravasate. In this
      review, recent advances made in understanding lymphocyte extravasation,
      interactions between lymphocytes and vascular endothelial cells, receptors on
      lymphocytes which are involved in their movement through the extracellular
      matrix, and cytokines, which regulate lymphocyte mobility through tissue, are
      described. In pathologic conditions, lymphocyte extravasation may be compromised,
      and delivery of immune effector cells to the site of injury is an important
      therapeutic end point. Adoptive therapy of solid tumors with antitumor effector
      cells depends on their successful delivery to the tumor. Although parameters
      which determine this delivery are not yet defined, considerable progress has been
      made in studies of the mechanisms involved in lymphocyte movement through
      tissues.

PMID- 1399402
TI  - Exploring the boundaries between lymphocyte traffic and tumor metastasis.

PMID- 1399404
TI  - Hyaluronic acid in the rabbit cornea after excimer laser superficial keratectomy.
AB  - Hyaluronic acid (HA) is not normally found in the corneal stroma. Rabbit corneas
      were examined for the presence of stromal HA after excimer laser treatment. One
      eye in each of 28 rabbits received a 60 microns deep superficial keratectomy with
      the excimer laser. After 1, 8, 21, and 60 days, the corneas were analyzed by
      quantitative and histochemical methods specific for HA. A statistically
      significant increase in the HA concentration compared to the baseline amount in
      the untreated fellow eye was seen at 8, 21, and 60 days. HA was visualized
      histochemically in the anterior stroma of the excimer-treated eyes at all times
      tested. The presence of HA after excimer surgery may influence the hydration,
      thickness, and transparency of the cornea. The reactive production of HA in the
      stroma may represent a nonspecific corneal tissue response to injury.

PMID- 1399403
TI  - Lymphocyte migration through extracellular matrix.
AB  - The movement of lymphocytes through extracellular matrix (ECM) is an essential
      component of normal traffic and infiltration into inflammatory sites. This review
      surveys current knowledge of the mechanisms of lymphocyte migration through ECM,
      most of which was derived from work with in vitro models of basement membranes,
      interstitial stroma, or their constituent components. Normal lymphocyte motility
      is an extremely plastic property. Naive lymphocytes tend to be unresponsive to
      ECM components and many chemoattractants, but when exposed to antigens,
      artificial mitogens and certain lymphokines, they rapidly acquire locomotory
      capacity, which is expressed as increased polarity, adhesiveness, invasiveness
      and chemotactic response. Acquisition of locomotory capacity is associated with
      the G0/G1 transition, and activation of protein kinase C appears to be a key
      event. Preliminary evidence indicates that mitogenesis and differentiation to the
      memory phenotype trigger a long-lasting, possibly permanent elevation of
      locomotory response to ECM. Receptors for fibronectin, laminin and collagens I
      and IV have been implicated as mediators of lymphocyte motility, but these
      receptors have not been characterized in detail. Heparanases facilitate T cell
      movement through the basement membrane, but the role of proteases has not yet
      been defined. Major gaps remain in our understanding of the connection between in
      vitro models and specific stages of the infiltration process in vivo and of
      motility regulation at the molecular level.

PMID- 1399405
TI  - Topical antibiotic therapy for the treatment of experimental Staphylococcus
      aureus keratitis.
AB  - A rabbit model of Staphylococcus aureus keratitis was developed to study the
      chemotherapeutic efficacy of ciprofloxacin, vancomycin, and cefazolin.
      Intrastromal injection of 100 colony forming units of log phase S. aureus ATCC
      strain 25923 resulted in rapid growth in the cornea, peaking at 10(7) cfu/cornea
      by 12 hr post-infection. Slit-lamp examination revealed that infected eyes
      reached 30% of maximum inflammation by 10 hr and 60% by 22 hr post-infection.
      Antibiotic therapy (one drop every 15 min for 5 hr) was initiated at 4 hr post
      infection (experiment 1) or 10 hr post-infection (experiment 2). Another group
      was initiated at 10 hr post-infection and treated for 10 hr (experiment 3). In
      experiment 1, treatment from 4-9 hr post-infection with 0.3% ciprofloxacin drops
      decreased the cfu per cornea 6.1 logs, compared to placebo-treated controls (P =
      0.0001), and rendered 50% of inoculated eyes sterile. Vancomycin (5.0%) and
      cefazolin (5.0%) each lowered the cfu per cornea 4.6 logs (P = 0.0187) but did
      not sterilize any eyes. In experiment 2, therapy from 10-15 hr post-infection
      with 0.3% ciprofloxacin reduced the cfu per cornea 0.9 logs (P = 0.0001).
      Vancomycin (5.0%) and cefazolin (5.0%) decreased the cfu per cornea 0.2 logs (P =
      0.3973) and 0.3 logs (P = 0.1307), respectively. In experiment 3, therapy from 10
      20 hr post-infection with 0.3% ciprofloxacin reduced the cfu per cornea 3.9 logs
      (P < 0.0001). In this keratitis model, ciprofloxacin was more effective than
      vancomycin or cefazolin in killing S. aureus.

PMID- 1399406
TI  - A new in vitro corneal preparation to study epithelial wound healing.
AB  - Corneal epithelial wound healing is an important process necessary for
      maintenance of visual integrity. Corneal epithelial wound healing occurs by
      cellular migration and proliferation. However, the molecular basis of
      reepithelialization is not known. To investigate individual molecular
      contributions to the wound healing process, an in vitro corneal preparation
      comparable to the in vivo condition is needed. This investigation developed a new
      whole mount in vitro rabbit cornea preparation and studied epithelial wound
      healing rates for epithelial and subepithelial wounds. The wound closure rates
      obtained in this study for epithelial and subepithelial wound healing (52 +/- 14
      microns/hr and 38 +/- 7 microns/hr, respectively) are comparable to in vivo rates
      of wound healing determined by other laboratories for rabbits. This preparation,
      achieved by functionally separating the epithelial and endothelial sides of the
      cornea, allows application of agents to the cornea in a manner that approximates
      the in vivo condition. This in vitro system is promising for future studies
      designed to investigate corneal wound healing while reducing potential ocular
      discomfort associated with in vivo corneal wounding.

PMID- 1399407
TI  - Concentration-dependent effects of lidocaine on corneal epithelial wound healing.
AB  - Local anesthetic toxicity is a recognized clinical problem that has limited the
      use of topical corneal anesthetics for pain relief after corneal abrasion.
      Studies have shown clinically administered concentrations (0.5-2%) of local
      anesthetics impair corneal reepithelialization. Unfortunately, instillation of
      local anesthetic drops into an eye does not provide a measurable, steady-state
      concentration of drug. Thus, it has not been possible to evaluate whether there
      is an analgesic concentration of local anesthetic that does not impair corneal
      wound healing. Using the new in vitro rabbit cornea wound healing model, the
      effect of steady-state lidocaine concentrations on epithelial wound healing was
      examined. At lidocaine concentrations below 100 micrograms/ml, wound healing was
      not impaired. Higher concentrations (250-1000 micrograms/ml) resulted in dose
      dependent impairment of epithelial wound healing. Combined with
      electrophysiologic evidence that corneal nerve injury discharge can be abolished
      by lidocaine concentrations less than 100 micrograms/ml, this research suggests
      that topical lidocaine in low concentration may be a safe topical corneal
      analgesic.

PMID- 1399408
TI  - Rabbit corneal epithelial cells adhere to two distinct heparin-binding synthetic
      peptides derived from fibronectin.
AB  - Fibronectin plays an important role in corneal reepithelialization during corneal
      wound healing. In this study, rabbit corneal epithelial (RCE) cell adhesion to
      fibronectin was further defined using proteolytic fragments of fibronectin and
      chemically synthesized peptides derived from the amino acid sequence of
      fibronectin. RCE cells adhere to intact fibronectin, the 75 kD fragment
      containing the RGDS (Arg-Gly-Asp-Ser) cell adhesion-promoting sequence, and the
      33/66 kD cell adhesion promoting/heparin-binding fragments of fibronectin. The 75
      kD fragment and the 33/66 kD fragments partially inhibited RCE cell adhesion to
      intact fibronectin, suggesting that these fragments represent distinct sites used
      by RCE cells to adhere to intact fibronectin. Two chemically synthesized peptides
      derived from the amino acid sequence of the 33/66 kD fragments of fibronectin, FN
      C/H-I (YEKPGSPPREVVPRPRPGV) and FN-C/H-III (YRVRVTPKEKTGPMKE), directly promoted
      the adhesion of RCE cells. As further evidence that FN-C/H-I and FN-C/H-III play
      a role in the adhesion of RCE cells to the 33/66 kD fragments of fibronectin, we
      have shown that soluble FN-C/H-I and FN-C/H-III inhibited RCE cell adhesion on
      surfaces coated with the 33/66 kD fragments. In addition, polyclonal IgG against
      FN-C/H-I and FN-C/H-III partially blocked RCE cell adhesion to the 33/66 kD
      fragments, confirming that these sequences represent adhesion-promoting sites
      within these fragments. In contrast, two previously described peptides from the
      33/66 kD fragments of fibronectin, which promoted the adhesion of a variety of
      cell types, FN-C/H-II (KNNQKSEPLIGRKKT) and CS-1 (DELPQLVTLPHPNLHG-PEILDVPST),
      did not support RCE cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399409
TI  - Formation of capillary-like tubes by vascular endothelial cells cocultivated with
      keratocytes.
AB  - This report describes an in vitro system that could be useful for investigating
      corneal neovascularization. When isolated bovine capillary endothelial cells
      (CEC) were cocultivated with rabbit corneal keratocytes, capillary-like cords
      extended actively from the endothelial cells in the multilayers of the
      keratocytes. The developing cords continued to elongate, branch out, and
      anastomose with each other, forming a capillary-like network by the 12th day of
      coculturing. Electron microscopic observation revealed that the cords were
      tubular structures composed of three to seven endothelial cells in the
      multilayers of keratocytes, and that a basal lamina-like matrix was situated at
      the abluminal face of the endothelial cells. The growth of cellular cords from
      the cloned CEC also occurred when CEC were seeded onto a cell-free extracellular
      matrix that had been synthesized by keratocytes. Keratocyte-conditioned medium
      alone did not stimulate proliferation of CEC. These observations clearly indicate
      that the formation of capillary-like structures by CEC depended upon the presence
      of an extracellular matrix produced by keratocytes, rather than upon the
      keratocytes themselves or any other keratocyte byproduct. This simple in vitro
      experimental system is proposed as a useful tool for studying corneal
      neovascularization.

PMID- 1399410
TI  - Intracellular pH regulation in fresh and cultured bovine corneal endothelium. II.
      Na+:HCO3- cotransport and Cl-/HCO3- exchange.
AB  - The comparison of intracellular pH (pHi) regulation between fresh (FBCE) and
      cultured (CBCE) bovine corneal endothelium was extended to HCO3- transport
      mechanisms. Upon introduction of CO2/HCO3- Ringer's solution, there was a small,
      sharp acidification followed by an alkalinization .09 and .18 pH U above the HCO3
      free resting pHi for FBCE and CBCE, respectively. This increase in pHi totally
      depended upon the presence of Na+, independent of Cl- and blocked by the anion
      transport inhibitor, H2DIDS (0.5 mmol/l). Recovery from an (NH4)2SO4-induced acid
      load also was blocked by Na+ removal and inhibited 62% and 84% by 0.5 mmol/l
      H2DIDS for FBCE and CBCE, respectively. These results indicate the presence of a
      Na+ dependent HCO3- transporter. Additions of 22 mmol/l K+ or 5 mmol/l Ba2+ led
      to substantial H2DIDS-inhibitable base influx in HCO3- Ringer's, which was
      significantly reduced in the absence of HCO3- for FBCE and CBCE, consistent with
      the presence of electrogenic Na+:nHCO3- cotransport. Using the Na+ sensitive
      intracellular dye, SBFI, we confirmed that the addition of HCO3- resulted in a
      H2DIDS-sensitive Na+ influx. The mean steady-state [Na+i] = 14 +/- 3 mmol/l in
      bicarbonate-free Ringer's and 31.5 +/- 2 mmol/l in CO2/HCO3-. HCO3- induced Na+
      influx was reduced 74% by 0.5 mmol/l H2DIDS. Removal of Cl- from bicarbonate
      Ringer's alkalinized FBCE and CBCE by .12 +/- .01 and .21 +/- .03, respectively.
      The increased pHi was completely blocked by 0.5 mmol/l H2DIDS. Similar
      alkalinizations were seen when Cl- was removed from air equilibrated bicarbonate
      free Ringer's. However, because of the lowered buffering capacity in the absence
      of HCO3-, the flux was reduced by 80%. Cl- free alkalinizations were eliminated
      by equilibrating the bicarbonate-free Ringer's with 100% nitrogen gas, indicating
      that residual CO2 can act as a substrate. Bicarbonate efflux on readdition of Cl-
      was Na+ independent and pHi sensitive (inactivated by low pHi), and showed simple
      saturating kinetics with respect to bath Cl, K1/2 = 22 and 16 mmol/l for FBCE and
      CBCE, respectively. These data are consistent with the presence of Cl-/HCO3-
      exchange in FBCE and CBCE. Application of 0.5 mmol/l H2DIDS to resting cells in
      HCO3- Ringer's significantly reduced pHi by .23 +/- .03 and .18 +/- .02 in FBCE
      and CBCE, respectively, indicating net HCO3- influx in resting cells and
      suggesting that the stoichiometry of the Na+:nHCO3- cotransporter favors Na+ and
      HCO3- uptake, ie, n < or = 2.

PMID- 1399411
TI  - Central and peripheral corneal thickness in full-term newborns by ultrasonic
      pachymetry.
AB  - To establish a standard of normality, the authors studied the central and
      peripheral (superior, inferior, nasal, and temporal) corneal thickness of 152
      healthy, white race, full-term newborns (304 eyes) between 1 and 6 days old,
      using ultrasonic pachymetry. The mean central corneal thickness (CCT) was 585 +/-
      52 microns (ranging from 446-706 microns). The mean peripheral corneal thickness
      (PCT), significantly thicker than CCT (P = 0.0001), was: superior (SCT) 696 +/-
      55 microns, inferior (ICT) 744 +/- 62 microns, nasal (NCT) 742 +/- 58 microns,
      and temporal (TCT) 748 +/- 55 microns. The SCT was significantly thinner than the
      ICT, NCT, and TCT (P = 0.0001). Differences among ICT, NCT, and TCT were not
      statistically significant. The mean CCT of the 1-day-old group was 611 +/- 58
      microns, this being thicker than those of the other age groups (P = 0.0001). The
      differences between male and female babies and between right and left eyes were
      not statistically significant. This is the first study on peripheral corneal
      thickness at the limbus in the four meridians in live newborns.

PMID- 1399412
TI  - Visual function and the subsequent development of exudative age-related macular
      degeneration.
AB  - The eyes of 47 subjects with exudative age-related macular degeneration in the
      fellow eye were tested with a battery of visual function tests at baseline and
      followed for at least 18 mo. Fundus photographs also were obtained at baseline.
      These photographs were used to verify the absence of exudative lesions in the 47
      eyes tested. Functional and funduscopic baseline data each were compared against
      outcome data obtained typically at 18 mo. The baseline data were analyzed for
      their ability to distinguish eyes that had developed detectable exudative age
      related macular degeneration from eyes that had not. Eyes with relatively slow
      foveal dark adaptation rates despite low foveal quantum absorption capabilities
      (as inferred from the effects of test area on the Rayleigh color match) were
      especially likely to develop subretinal neovascularization. The resulting
      sensitivity/specificity and odds ratios were comparable to those of the most
      effective funduscopic risk indicators. Low S (blue) cone-mediated sensitivity
      also was associated with an exudative outcome.

PMID- 1399413
TI  - Immunogold localization of myosin in the photoreceptor cilium.
AB  - The photoreceptor outer segment (OS) develops from the distal end of a nonmotile
      cilium and exhibits a continuous renewal of its disc structures throughout life.
      Immunocytochemical studies have localized an actin-rich domain to the ciliary
      axoneme at the base of the OS, and recent ultrastructural studies of detergent
      extracted retinas have demonstrated actin filaments at this site. These filaments
      are believed to participate in the formation of new outer segment discs. In this
      study, rat neural retinas were treated with the detergent saponin, fixed with
      aldehydes, and embedded in London resin white resin for immunoelectron
      microscopy. In thin tissue sections, actin filaments were observed within the
      appropriate ciliary domain and these filaments could be positively stained with
      anti-actin antibodies. When this tissue was immunogold labeled with anti-myosin
      antibodies, myosin also was found in this locale. The results of this study
      demonstrate that saponin-extracted retinas can be used for immunoelectron
      microscopy studies of the photoreceptor cytoskeleton. In addition, the presence
      of myosin within the actin-filament-containing portion of the cilium suggests
      that an actomyosin contractile mechanism may play a role in outer segment disc
      morphogenesis.

PMID- 1399414
TI  - Transient increase of b-wave in the mouse retina after sodium iodate injection.
AB  - Twenty C57 black mice received an injection of 40 mg/kg of sodium iodate through
      the caudal vein. The electroretinograms (ERGs) were recorded before and after
      injection. Flash stimuli with the maximum illuminance, 30,000 lux, were given at
      increasing levels of illuminance in 0.6 log U steps for 13 levels of intensity.
      The a- and b-wave amplitudes increased linearly with increased stimulus intensity
      for approximately 5.0 log U before being saturated. Twenty four hours after
      injection, the intensity-amplitude curve shifted toward the higher intensity
      region. It was calculated that the sensitivity loss of the b-wave after injection
      was 2.0 log U, although the maximum amplitude was larger and the peak latency was
      delayed. The same results were seen less obviously in the ERGs 48 hr after
      injection. After 96 hr, both waves were greatly attenuated and even abolished. At
      the time the increased ERGs were recorded, the histopathologic findings exhibited
      severe damage of the retina in the pigment epithelium and in the outer layer.

PMID- 1399415
TI  - Impoverished stimulus input does not simulate the slowed visual kinetics of
      retinal damage.
AB  - In the rat with normal sight, the acoustic startle reflex to a sound burst is
      suppressed when the sound is preceded by a brief light pulse. This effect of
      light in the rat with retinal damage is reduced and peak suppression is seen at a
      greater delay. Both observations are expected consequences of the loss of visual
      sensitivity that should accompany photoreceptor loss. However, in an early stage
      of retinal damage, the peak of the suppressive effect is so delayed that at long
      lead times the light flash is a more effective stimulus in the rat with the
      damaged retina than in the normal rat. Two experiments tested the hypothesis that
      this crossing over of the two groups is a secondary consequence of a nonspecific
      loss of visual sensitivity in the visually impaired rat. If the hypothesis is
      correct, reductions in the intensity or duration of the light flash and the
      degree of dark adaptation should model the effect in normal rats. The overall
      amount of reflex suppression was diminished with these manipulations, but none
      diminished the temporal development of reflex suppression to a degree sufficient
      to produce the paradoxical crossover effect characteristic of retinal damage.
      These data indicate that decrements in the speed of visual processing are not
      secondary to the changes in sensitivity that accompany retinal damage, but should
      be viewed as a separate and independent form of visual impairment.

PMID- 1399416
TI  - Biodegradable microspheres containing adriamycin in the treatment of
      proliferative vitreoretinopathy.
AB  - The use of biodegradable polymer microspheres containing adriamycin for the
      treatment of proliferative vitreoretinopathy (PVR) in an experimental rabbit
      model was investigated. A single injection of microspheres containing 10
      micrograms of adriamycin effectively decreased traction retinal detachment to 10%
      (n = 10), whereas 50% of eyes injected with blank microspheres (n = 10) developed
      retinal detachment (P < 0.05). A single injection of microspheres, containing 3
      micrograms of adriamycin, did not suppress retinal detachment.
      Electroretinographic and histologic studies confirmed that the 10 micrograms
      injection of adriamycin in microspheres was not toxic to the retina, although the
      injection of the same amount of free adriamycin caused retinal necrosis and
      detachment. Thus, microspheres containing adriamycin hold promise as a new
      treatment modality for PVR.

PMID- 1399417
TI  - Superoxide dismutase in the anterior chamber and the vitreous of diabetic
      patients.
AB  - Total superoxide dismutase (SOD) activity was examined in the anterior humor of
      32 diabetic patients and 34 nondiabetic controls during cataract extraction.
      Median age (95% confidence interval) was 77.5 yr (73.3-81.0) and 79.3 yr (76.0
      83.2), respectively. The SOD activity also was examined in posterior vitreous
      sampled peroperatively in 10 diabetics with proliferative retinopathy and post
      mortem in seven diabetic patients and 35 nondiabetic controls. Ages were 57.2 yr
      (35.0-73.9), 74.4 yr (40.7-83.6), and 73.8 yr (65.0-80.2), respectively. In
      nondiabetic patients, the total SOD activity was much lower in the anterior
      chamber, 9.9 U/ml (8.1-12.6), than in the posterior vitreous, 106.3 U/ml (range
      65.6-119.0), P < 0.001. We found no difference between the SOD levels in the
      anterior chamber of nondiabetic controls and diabetic patients, who had 9.6 U/ml
      (7.6-13.7). The SOD activity in posterior vitreous in diabetic patients sampled
      peroperatively, 23.9 U/ml (8.9-39.2), P < 0.0001, and post-mortem, 39.5 U/ml (6.5
      214.2), P < 0.04, was significantly lower than in the controls sampled post
      mortem, 106.3 U/ml (65.6-119.0). Low levels of SOD in the anterior chamber may be
      involved in cataract development, in diabetic patients and nondiabetic controls.
      That diabetics had decreased SOD activity in the posterior vitreous points to a
      possible role of SOD in the complex process of diabetic retinopathy development.

PMID- 1399418
TI  - Mid-frequency loss of foveal flicker sensitivity in early stages of age-related
      maculopathy.
AB  - Temporal contrast sensitivity in eyes at risk for exudative age-related
      maculopathy (ARM) was compared to that in age-matched healthy older eyes. The
      test stimulus was a foveally viewed, flickering, long-wavelength 2.8 degrees
      diameter circle in an equiluminant (photopic) surround. Retinal illuminance and
      decision criterion differences were experimentally controlled. Eyes in the
      healthy and ARM-risk groups had 20/30 or better Snellen acuity and intraocular
      pressure of less than 22 mmHg. Nevertheless, the ARM-risk patients were less
      sensitive to flicker contrast, especially for mid-temporal frequencies. This
      suggests that flicker sensitivity may be useful in identifying patients at risk
      for exudative ARM. In addition, comparison with other research reveals a paradox:
      Mid-temporal frequency sensitivity losses may be attributable primarily to a
      "high temporal frequency" mechanism.

PMID- 1399419
TI  - Foveal flicker sensitivity discriminates ARM-risk from healthy eyes.
AB  - The "good" eyes of 13 patients with monocular exudative ARM were compared with
      age-matched healthy eyes of 19 subjects. Membership in the two study groups was
      based upon careful clinical evaluation of the tested eye as well as upon status
      of the fellow eye. We asked whether temporal contrast sensitivity for a long
      wavelength, low spatial frequency stimulus can be used to identify the group in
      which a given eye belongs. Using step-wise discriminant analysis, we found that
      the ARM-risk and healthy eyes could be classified with 78% accuracy on the basis
      of foveal flicker sensitivity at two temporal frequencies--14 and 10 Hz (in order
      of estimated weight.)

PMID- 1399420
TI  - Preliminary evaluation of flicker sensitivity as a predictive test for exudative
      age-related maculopathy.
AB  - Flicker contrast sensitivity was tested in the "good" eyes of 13 patients with
      monocular exudative age-related maculopathy (ARM). The stimulus was a foveal,
      long-wavelength, low spatial frequency 2.8 degrees circle in an equiluminant
      (photopic) surround. Two of these ARM-risk eyes have since developed exudative
      ARM. Compared to healthy age-matched eyes, the two eyes that developed exudative
      ARM had significantly lower sensitivity at 10-40 Hz up to 9 mo before exudative
      symptoms appeared. The implications of these results regarding the time-course of
      ARM and the predictive value of foveal contrast sensitivity testing are
      considered. Based upon data and theoretical considerations, the authors speculate
      that sensitivity loss between 10 and 40 Hz is a good predictor of which eyes will
      develop exudative ARM. This proposal will be tested by new data from current as
      well as new ARM-risk subjects.

PMID- 1399421
TI  - Infant VEP and preferential looking acuity measured with phase alternating
      gratings.
AB  - Previously, infants' grating acuity was found to be temporally tuned, but adults'
      grating acuity was not. In infants, acuity was higher for gratings phase
      alternating at 7.5 and 14 reversals/sec than for stationary gratings and gratings
      alternating at 2.5 or 23 reversals/sec. Also, when preferential looking (PL) and
      visually evoked potential (VEP) acuity were estimated with phase alternating
      gratings (14 reversals/sec), the acuity difference between the two techniques was
      smaller than that obtained when phase alternating gratings were used to estimate
      VEP acuity and stationary gratings were used to estimate PL acuity. In the
      present study, it was determined if PL grating acuity was tuned in older children
      and if the smaller difference between VEP and PL acuity found when infants were
      tested with phase alternating gratings was independent of temporal rate. Grating
      acuity in infants older than 2 yr was found to be not tuned, and the smaller
      difference between VEP and PL grating acuity in infants when both were measured
      with phase-alternating gratings was not rate dependent. VEP acuity and PL acuity
      for phase alternating gratings developed at different rates, converging to nearly
      equivalent levels by 12 mo of age.

PMID- 1399422
TI  - Assessment of physiologic statokinetic dissociation by automated perimetry.
AB  - The effects of age, stimulus size, meridian, and eccentricity on physiologic
      statokinetic dissociation were investigated in clinically normal subjects using
      the Humphrey field analyzer (HFA, model 640), an automated perimeter capable of
      both static and kinetic perimetry. The right eyes of 20 age-matched young and 20
      age-matched elderly volunteers was examined along the 15 degrees and 195 degrees
      meridians with six Goldmann size I and five size III kinetic stimuli. These were
      chosen to produce a spread of discrete eccentricities. Kinetic sensitivity was
      determined seven times for each stimulus, and the mean stimulus locations were
      expressed in terms of their x and y coordinates. Static sensitivity for each
      stimulus size then was determined seven times at each of the corresponding
      locations using a custom threshold program. The area under each sensitivity
      gradient was determined using the trapezium rule. Group mean kinetic sensitivity
      was greater than group mean static sensitivity (P < 0.001), and this difference
      was largely independent of age, stimulus size, meridian, and eccentricity.

PMID- 1399423
TI  - Comparison of computer-assisted versus manual optic nerve head pallor
      measurement.
AB  - Computerized methods of examining the optic nerve head offer the possibility of
      providing consistent, reliable, and accurate measurements of the nerve head. The
      reliability and accuracy of such instruments must be examined to confirm this.
      This research was undertaken to gain an insight into the accuracy of such a
      system, which takes its measurements by tracking the luminance boundaries of the
      pallor area and the optic nerve head after an observer marks the starting points.
      Measurements made using the computer-tracked boundary were compared with those
      made using a boundary tracked by an image-processing system of greater
      sophistication, the human visual system. The comparison was made with images from
      one eye from each of 30 subjects (10 normal, 10 ocular hypertensive, and 10
      glaucomatous). The measurements were made by two observers. Each observer made
      each set of measurements twice, and the results were analyzed with a five-factor
      analysis of variance. The measurements made using the computerized method did not
      differ significantly from those made using the manual boundary tracking for the
      two observers, and they were highly correlated (r = 0.99 for the area pallor-disc
      ratio). Significant differences (P < 0.05) were found between the two observers
      in both the manual and computerized boundary tracking. The computerized method,
      however, did not find differences between the two sets of measurements made by
      each observer; the manual method did show such differences. The computerized
      method appeared to trace the luminance boundaries successfully in the image, and
      it might reduce errors related to the observer marking the starting points on
      different occasions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399424
TI  - Effect of acute increases in intraocular pressure on intravascular optic nerve
      head oxygen tension in cats.
AB  - A newly developed phosphorescence imaging technique was used to generate two
      dimensional maps of intravascular oxygen tension (PO2) in the optic nerve head
      (ONH) and retina of the cat to study the effects of acute moderate increases in
      intraocular pressure (IOP) on the ONH and retinal PO2. Both the ONH and retinal
      PO2 were remarkably well maintained as the IOP increased; hypoxia developed only
      after the blood flow to the eye was stopped. Because ONH hypoxia was not observed
      during IOP elevation, a lack of oxygen may not be a major cause of glaucomatous
      damage, although the effects of chronically elevated IOP on the PO2 remain to be
      evaluated. Because this imaging technique was noninvasive and required only a
      small bolus injection of a nontoxic oxygen probe, the authors anticipate that it
      will find significant application in the study of many ocular vascular diseases
      and glaucoma.

PMID- 1399425
TI  - Autosomal dominant mouse cataract (Lop-10). Consistent differences of expression
      in heterozygotes.
AB  - The clinical and histologic features are reported of an autosomal dominant mouse
      cataract that was first observed as a new mutation in a cross between BALB/cJ and
      AKR/J. In the homozygous state, the eyes were microphthalmic, and a dense white
      cataract was present when the eyes opened at day 12. Histologic changes were
      apparent from birth and as early as 18 days' gestation. Liquefaction started by
      day 4, and herniation of lens contents posteriorly was seen at day 11.
      Heterozygous mice had variable expression depending both on their genetic
      background and age. When the single gene was expressed fully, the cataract
      appeared as a fetal nuclear white opacity; partial expression gave a nuclear haze
      to snowflake nuclear opacities. Lop-10 appeared to be an excellent model for
      studying variable expression of a dominant gene.

PMID- 1399426
TI  - Cellular architecture in age-related human nuclear cataracts.
AB  - Age-related or senile human nuclear cataracts were examined using electron
      microscopy of thin sections prepared from thick vibrating-knife microtome
      sections of nuclei extracted by extracapsular surgery. The use of extended
      aldehyde-tannic acid fixation of 80-120-microns thick vibrating-knife microtome
      sections overcame the difficult problem of preserving the hardened nuclear core
      of aged lenses. Comparisons were made between a typical nuclear cataract,
      containing a central opacity and a transparent rim, and a more advanced, or
      mature, completely opaque nuclear cataract. The typical nuclear cataract
      contained no obvious cell disruption, cellular debris, or objects that readily
      could explain the central opacity. The fiber cells had intact uniformly stained
      cytoplasms with well-defined plasma membrane borders and gap junctions. The
      transparent rim and the nuclear core appeared similar, except that fiber cells in
      the nucleus were more condensed with more elaborate intercellular
      interdigitations. The mature cataract showed various types of cell disruption in
      the perimeter but not in the core of the nucleus. These disruptions were
      globules, vacuoles, multilamellar membranes, and clusters of highly undulating
      membranes. Because these potential scattering centers were not found in the
      nuclear core, they probably were not the sole cause of the observed opacity.
      Other potential scattering centers found throughout the mature cataract nucleus
      included variations in staining density between adjacent cells, enlarged
      extracellular spaces between undulating membrane pairs, and protein-like deposits
      in the extracellular space. Similar features, although less pronounced, were
      present in the typical nuclear cataract. It was concluded that massive cell
      disruption is not essential to the formation of a central nuclear opacity. Subtle
      structural changes, especially small fluctuations in protein density between
      adjacent cells and alterations of the membranes and the extracellular space,
      probably contribute significantly to the central opacities in human nuclear
      cataracts.

PMID- 1399427
TI  - Verapamil substantially increases the chemomyectomy effect of doxorubicin
      injected into rabbit or monkey eyelid.
AB  - Local doxorubicin injections have been used clinically to treat blepharospasm,
      hemifacial spasm, and other related disorders permanently and nonsurgically.
      Doxorubicin is an effective myotoxic agent for the removal of the orbicularis
      oculi muscle in the eyelid after local injection. Injections of this drug alone
      resulted in removal of up to 70% of the muscle fibers from the treated eyelids in
      monkeys. The authors attempted to optimize the conditions for doxorubicin
      myotoxicity of the orbicularis oculi. Doxorubicin was injected shortly after
      local verapamil injection in rabbits and a monkey in an attempt to maximize the
      muscle injury in the eyelid. Verapamil (dose, 0.5 mg or 1.6 mg in the rabbits),
      injected with a range of doses of doxorubicin, caused substantially increased
      muscle loss in the eyelid compared with doxorubicin alone. In the monkey,
      verapamil (dose, 0.25 mg) injection was followed by an injection of 1 mg of
      doxorubicin. Verapamil cotreatment resulted in increased muscle loss over that
      caused by doxorubicin alone in both rabbits and the monkey. Injection of
      verapamil alone also caused muscle loss, and this was quantified. The muscle loss
      with doxorubicin and verapamil injections included muscle in the preseptal
      portion of the muscle and even in the pretarsal muscle (which previously was
      difficult to destroy). This technique clinically might be used to decrease the
      dose of doxorubicin injected and/or decrease the total number of injections
      necessary but still retain a clinically effective treatment for blepharospasm and
      hemifacial spasm. The reduction in the dose of doxorubicin also may decrease the
      risk of skin injury from doxorubicin chemomyectomy in these patients.

PMID- 1399428
TI  - Cytoskeletal antigen expression in ocular mucosa-associated lymphoid tissue.
AB  - The human lacrimal gland (LG) and ocular surface contain discrete regions of
      epithelial cells with specific functions and at different stages of cellular
      differentiation. Epithelial cells contain cytoskeletal antigens that show a
      differentiation-dependent pattern of expression. The objective of this study was
      to characterize the various epithelial cell populations in normal human ocular
      mucosa-associated lymphoid tissue (MALT; LG, conjunctiva, and cornea) based on
      their immunohistochemical staining patterns with anticytoskeletal monoclonal
      antibodies (MoAbs) reactive with cytokeratins (AE-1, AE-2, AE-3, AE-5, AE-14,
      PKK1, and 34 beta E12), muscle-specific actin (HHF35), and vimentin. AE-1 stained
      LG (acini, ducts, and myoepithelia) and the full thickness of corneal and
      conjunctival epithelia. It stained only the superficial and basal limbal
      epithelium. AE-2 weakly stained all epithelia, except LG acini and proximal
      intralobular ducts. AE-3 and 34 beta E12 MoAbs had strong immunoreactivity with
      all MALT epithelia. AE-5 strongly stained the inner cells (suprabasal) of LG
      central intra- and interlobular ducts and the suprabasal epithelial layers of the
      cornea. It weakly stained LG myoepithelia and the superficial conjunctival
      epithelium. AE-14 stained the outer (basal) cells of LG central intra- and
      interlobular ducts, LG myoepithelia, basal epithelial layers of the limbus and
      conjunctiva, and all corneal epithelia. PKK1 stained all epithelia, except the
      basal limbus. HHF35 and the antivimentin MoAbs stained only the LG myoepithelia.
      The results of these studies indicate that the different epithelia in human
      ocular MALT may be differentiated by specific patterns of immunoreactivity with
      anticytoskeletal MoAbs. These MoAbs may be useful molecular markers for
      identifying ocular MALT epithelia.

PMID- 1399429
TI  - Dietary essential fatty acid supply and visual acuity development.
AB  - The influence of dietary omega-3 fatty acid supply on visual acuity development
      was evaluated in very low birth weight (VLBW) infants using visual-evoked
      potential (VEP) and forced-choice preferential-looking (FPL) procedures at 36 and
      57 wk postconception. The VLBW infants born at 27-33 wk postconception were
      randomized to one of three diet groups: corn oil, which provided solely linoleic
      acid; soy oil, which provided linoleic and alpha-linolenic acids; or soy/marine
      oil; which was similar to the soy oil formula but also provided preformed long
      chain omega-3 fatty acids. The VLBW infants in the soy/marine oil group had
      higher omega-3 levels in erythrocyte membranes and better VEP and FPL acuities at
      36 and 57 wk than infants in the corn oil group. The soy oil group had
      intermediate omega-3 levels in erythrocyte membranes and significantly poorer VEP
      acuity at 57 wk compared with the soy/marine oil group. Only the soy/marine oil
      group had acuities comparable to the "gold standards" of VLBW infants fed human
      milk and preterm infants who were born and tested at 35-36 wk postconception. In
      addition, VEP and FPL acuity were poorer in a nonrandomized group of formula-fed
      full-term infants than in breast-fed full-term infants. The results suggest that
      dietary omega-3 fatty acid supply may play an important role in early human
      visual development.

PMID- 1399430
TI  - Effects of angiographic needle size and subsequent catheter insertion on arterial
      walls. An in vitro experiment in human cadavers.
AB  - RATIONALE AND OBJECTIVES: It is widely believed that down-sizing catheters, and
      possibly needles, will decrease damage to the entry vessel in the performance of
      angiography. The purposes of this in vitro experiment are to determine if smaller
      needles produce less arterial wall damage than larger needles and to assess the
      influence of subsequent catheter insertion. METHODS: Each iliac artery pair from
      35 fresh human cadavers was punctured three times with an 18-g needle and three
      times with a 21-g needle, for a total of 210 punctures. In two of each set of
      three, a 5- or 7-F dilator was passed. One hundred ninety-eight puncture tracts
      were usable and examined microscopically. They were graded on a scale of 1 to 3
      in each of four categories: size of tract, margin irregularity, approximation of
      edges, and shape of tract. RESULTS: Chi-square analysis of the grading scores
      showed a significant shift of cases into lower damage grades when the smaller
      gauge needle was used for initial punctures (P < .0005). The subsequent insertion
      of a dilator, however, imposed further damage, such that the initial differences
      due to needle gauge were obliterated (P > .2). CONCLUSION: These data indicate
      that a 21-g needle produces less arterial wall damage than an 18-g needle, but
      that any safety conferred by the smaller needle is eliminated by the subsequent
      insertion of a 5- or 7-F catheter.

PMID- 1399431
TI  - Efficacy of metaiodobenzylguanidine as a scintigraphic agent for the detection of
      neuroblastoma.
AB  - RATIONALE AND OBJECTIVES: Metaiodobenzylguanidine (MIBG) has been shown to be
      both sensitive and highly specific for the detection of neuroblastoma. However,
      controversy surrounds its sensitivity in detecting neuroblastoma when compared
      with radionuclide (technetium 99m-methylene diphosphonate [99mTc]-MDP) bone
      scans. Because a diagnostic test ideally should be easy to interpret in addition
      to being sensitive and specific, this study aims to determine the most
      efficacious scintigraphic agent for diagnostic use in neuroblastoma. METHODS:
      Twenty patients with neuroblastoma had a total of 26 paired MIBG and 99mTc-MDP
      bone scans obtained less than 4 weeks apart. Each study was evaluated
      independently of its counterpart by six separate observers (3 experienced and 3
      inexperienced in MIBG scintigraphy) to determine the presence or absence of
      disease and the tumor burden. RESULTS: Inexperienced observers reported more
      confidence in their interpretations of 99mTc-MDP bone scans; however, seven false
      positive bone scans were reported. Using MIBG, all true-positive and true
      negative scans, as well as significantly more sites of both primary and
      metastatic disease, were identified by all observers. CONCLUSION: This study
      suggests that MIBG is the more efficacious agent for the scintigraphic evaluation
      of neuroblastoma.

PMID- 1399432
TI  - The estimate of glomerular filtration rate during urography. Acceptability of a
      nonionic contrast medium as a marker of renal function.
AB  - RATIONALE AND OBJECTIVES: An estimate of glomerular filtration rate (GFR) may be
      obtained at the same time as urography by measuring the plasma clearance of the
      radiographic contrast medium using an x-ray fluorescence technique. It must be
      established whether the function measured or one modified by an effect of the
      contrast medium itself represents a true value. METHODS: Technetium 99m-DTPA
      (99mTc-DTPA) plasma clearance was measured in 21 patients using a single
      injection technique, before, during, and after an intravenous injection of 50 mL
      of 350 mg I/mL iohexol. Iohexol clearance also was determined using an
      alternative single-injection, two-sample technique. RESULTS: The mean 99mTc-DTPA
      clearances before, during, and after contrast were 71.2, 71.5, and 70.7
      mL/minute, respectively. The within-patient standard deviation in clearance
      values was 3.84 mL/minute. One factor repeat measures analysis of variance
      indicated no significant difference between the three measurements (F ratio =
      0.24). Contrast and 99mTc-DTPA clearances performed simultaneously agreed closely
      (r = .976; ClDTPA = 1.02ClCon - 1.35). CONCLUSION: The authors conclude that no
      change in function is observed during or 48 hours after contrast injection.
      Imaging doses of iohexol can be used for GFR measurement during urography.

PMID- 1399433
TI  - Impact of a primary reader's opinion on the detection of rib fractures.
AB  - RATIONALE AND OBJECTIVES: The authors assessed the influence of a prior reader's
      opinion on the detectability of rib fractures. METHODS: Six pairs of observers
      read the chest PA radiographs of 92 subjects with rib fracture(s) and 28 normal
      subjects to detect rib fracture(s) according to a five-point rating of confidence
      with three methods. In method A, each reader read films as a primary reader. In
      method B, each reader read films after knowing his or her partner's opinion. In
      method C, each reader initially observed films and then made the final decision
      after knowing his or her partner's opinion. RESULTS: Methods B and C were
      superior to method A in sensitivity. There was no difference in performance
      between methods B and C. Method C required a significantly longer time than the
      other methods. CONCLUSION: Detection of rib fractures is improved by seeking the
      opinion of other observers.

PMID- 1399434
TI  - Fractal dimensions of ductal patterns in the parotid glands of normal subjects
      and patients with Sjogren syndrome.
AB  - RATIONALE AND OBJECTIVES: The sialographic ductal patterns of the parotid glands
      in patients with Sjogren syndrome were compared with those of normal patients by
      measuring the fractal dimensions. METHODS: Fractal dimensions were estimated
      using the modified pixel dilation method. RESULTS: The mean fractal dimension was
      1.64 +/- 0.06 for the normal glands and 1.39 +/- 0.10 for the glands with Sjogren
      syndrome (P < .005). No correlation between the age or sex and fractal dimension
      was observed for both groups. In Sjogren syndrome, a significant difference in
      the fractal dimension was observed between the subgroup having punctuate fillings
      with a diameter less than 1 mm and the subgroup from 1 to 2 mm (P < .001).
      CONCLUSION: The fractal dimension is useful as a numeric grading of the
      complexity of the ductal pattern and the progression of parotid disease.

PMID- 1399436
TI  - Sonographic changes during hepatic interstitial laser photocoagulation. An
      investigation of three optical fiber tips.
AB  - RATIONALE AND OBJECTIVES: Interstitial laser photocoagulation (ILP) destroys
      tumors thermally, using laser energy delivered from implanted optical fibers. The
      objectives of the study are to identify a fiber tip/delivered energy combination
      which produces lesions of useful size, visible on ultrasound (US) during ILP, and
      to compare ILP lesions and their US images. METHODS: Hepatic ILP was performed at
      laparotomy in six pigs, using three different fiber tips (cylindrical diffusing,
      spherical diffusing, plane-cut). US images were obtained during ILP, immediately
      after ("early" images), and before the animals were killed (2-2.5 hours, "late"
      images). Actual lesions were assessed histopathologically. RESULTS: Few US
      changes were seen around cylindrical diffusing and spherical diffusing tips until
      tip destruction. Plane-cut tips, at 1.5 to 2.0 W, produced prominent US images of
      the 1- to 2-cm thermal lesions. Early images tended to overestimate necrosis.
      Late images approximated necrosis. CONCLUSION: For US-controlled ILP, plane-cut
      tips are better than currently available cylindrical diffusing or spherical
      diffusing tips. Lesion image growth periods might enable control of lesion size.
      Further studies are needed to determine the consistency of the described
      relationship between lesion images and actual lesions.

PMID- 1399435
TI  - Extracorporeal liver ablation using sonography-guided high-intensity focused
      ultrasound.
AB  - RATIONALE AND OBJECTIVES: High-intensity focused ultrasound (HIFU) is the only
      radiation beam that can remotely destroy deep-seated tissue targets without
      causing damage to the intervening tissues. This study evaluates the ability of
      sonography-guided HIFU to extracorporeally induce liver ablation in a rabbit
      model. METHODS: Under sonographic guidance, the HIFU beam was transcutaneously
      focused at the target tissue in the liver through a subcostal approach. A
      computer controlled the HIFU exposure and transducer movement to destroy a
      preselected tissue volume. Simultaneous sonography monitored the tissue response.
      Ten insonated rabbits were killed from days 0 to 10, and the liver and
      intervening tissues were examined histologically. RESULTS: A sharply demarcated
      sonolesion of coagulation necrosis was produced in the liver in 9 of 10 animals.
      No damage was found in the intervening tissues (n = 6) when adequate acoustic
      coupling and proper beam path was applied. CONCLUSION: Sonography-guided HIFU
      might be a potential new modality for extracorporeal inducement of liver cancer
      ablation without resorting to laparatomy.

PMID- 1399437
TI  - Magnetic resonance imaging of the acute effects of interstitial neodymium:YAG
      laser irradiation on tissues.
AB  - RATIONALE AND OBJECTIVES: Laser irradiation therapy in deep tissues requires a
      monitoring method other than visual guidance. Magnetic resonance imaging (MRI)
      can be used for this purpose because it visualizes soft tissue structures and
      heat distribution. METHODS: The authors performed interstitial laser irradiations
      in rat livers with various laser outputs and measured the sizes of laser-induced
      lesions. MRI of these lesions was done ex vivo and compared with the histologic
      findings. Laser-induced lesions also were studied in rabbit brain, liver, and
      skeletal muscle to show the influences of tissue optical and thermal properties.
      Imaging of interstitial laser irradiation also was performed in vivo in rabbit
      brains. RESULTS: MRI depicted the laser-induced lesions produced with different
      laser outputs and tissue types. MRIs of rabbit brain in vivo effectively
      demonstrated the signal decrease during heating and acute tissue changes.
      CONCLUSION: MRI has potential for monitoring interstitial laser surgery or
      hyperthermia.

PMID- 1399438
TI  - Digital radiography with photostimulable storage phosphors. Control of detector
      latitude in chest imaging.
AB  - RATIONALE AND OBJECTIVES: A widely used digital radiography system based on a
      photostimulable storage phosphor (PSP) detector was analyzed with regard to
      radiographic contrast changes that result from the adjustment of detector
      latitude (x-ray sensitivity range) in the normal processing of chest images.
      METHODS: Images of an acrylic step wedge were acquired using the digital system
      in a mode that permitted direct control of effective detector latitude. The
      images were post-processed in conditions duplicating those used for portable
      chest examinations, and contrast was measured. RESULTS: Increases in effective
      detector latitude provided only marginal radiographic contrast gains in the
      subdiaphragm-equivalent areas of the laser-printed digital film image, while
      causing large reductions in radiographic contrast in the lung-equivalent region.
      CONCLUSION: Detector latitude is an important variable that should be monitored
      or controlled in investigations that compare reader performance using
      conventional and digital systems.

PMID- 1399439
TI  - Experimental pulmonary infarction in a pig model.
AB  - RATIONALE AND OBJECTIVES: The authors sought to develop a reliable animal model
      for experimental pulmonary infarction, to evaluate it with radiologic-pathologic
      correlation, and to determine the use of high-resolution computed tomography
      (HRCT) in monitoring parenchymal lung damage due to infarction. METHODS:
      Selective left lower lobe pulmonary artery occlusion was performed in seven
      Yorkshire pigs with transcatheter silicone elastomer injection. After occlusion,
      99m technetium (99mTc) macroaggregated albumin perfusion lung scans and
      sequential in vivo HRCT lung scans were obtained from days 0 to 46. The in vivo
      radiologic findings were correlated with specimen radiography, specimen HRCT, and
      histologic findings. RESULTS: A complete and permanent arterial occlusion was
      achieved, involving up to three orders of branching distal to the catheter. An
      anatomically defined perfusion defect was seen on 99mTc lung scans corresponding
      to the occluded area. HRCT changes consisted of confluent densities progressing
      to mixed alveolar and interstitial opacities within the first week after
      embolization. In the follow-up period, marked parenchymal clearing was observed.
      In all cases after pulmonary artery occlusion, the histologic findings were
      characteristic of pulmonary infarction and demonstrated alveolar edema,
      hemorrhage, limited alveolar wall damage, and septal thickening followed by
      residual fibrosis. CONCLUSION: Using this model, it is feasible to produce
      pulmonary infarction in the pig which may potentially be useful to study the
      pathophysiologic and radiologic changes of pulmonary infarction.

PMID- 1399440
TI  - Alteration of human tumor cell adhesion by high-strength static magnetic fields.
AB  - RATIONALE AND OBJECTIVES: The authors investigated whether the ability of human
      malignant melanoma cells to increase in cell number or their ability to remain
      viable was compromised by high-field strength static magnetic fields. Normal
      human fibroblasts also were studied to determine if any magnetic field-related
      alterations were unique to tumor populations. METHODS: Human cell lines were
      grown in monolayer culture in vitro and subjected to a static magnetic field
      using a 4.7-Tesla superconducting magnetic resonance imaging (MRI) magnet with
      the gradient coils removed. The number of cells within the total population was
      determined using an electronic particle counter. Cell viability was estimated by
      trypan blue exclusion, and the cellular morphology of the attached cells was
      documented using microscopy. RESULTS: Both the human malignant melanoma cells and
      the normal human cells were unaffected by the presence of a high-strength
      magnetic field in terms of increasing their cell numbers or their viability.
      However, the ability of the malignant melanoma cells to remain attached to the
      tissue culture surface was impaired. Normal fibroblasts were not affected in this
      regard. CONCLUSION: High-strength static magnetic fields alter the ability of
      human malignant melanoma cells to remain adherent to the tissue culture surface,
      but have no effect on normal human fibroblasts. This may affect the ability of
      tumor cells to successfully interact with their environment.

PMID- 1399441
TI  - Phantom evaluation of imaging modalities for silicone breast implants.
AB  - RATIONALE AND OBJECTIVES: Recent concern regarding possible adverse effects from
      silicone breast implants has increased the role of radiologists in assessing
      augmented breasts. The authors compare the commonly available imaging modalities
      in evaluating the intact silicone implant as well as free silicone in the
      adjacent tissue. METHODS: A contrast resolution phantom and breast of veal
      phantom were tested. Fat was used as a reference material. The phantoms were
      imaged with xeromammography, film-screen mammography, ultrasound, computed
      tomography (CT), and magnetic resonance imaging (MRI). Proton MRI spectroscopy
      also was performed on fat, silicone, water, and water/gelatin samples. The
      consensus of two radiologists determined whether free silicone was present.
      RESULTS: CT and MRI provided the best images of the implant and the free
      silicone. Several features of MRI were useful: spin-density scans and the fast
      low-angle shot (FLASH) and fast imaging with steady-state precision (FISP)
      techniques provided excellent resolution, a consistent chemical shift artifact
      appeared around the silicone, and frequency selective pre-saturation techniques
      resulted in marked suppression of the silicone. CONCLUSION: Additional testing in
      a more realistic setting, breast coil design, and improvement of various MRI
      techniques, particularly the frequency selective pre-saturation techniques, all
      appear promising in evaluating breast implants, the presence of free silicone,
      and the adjacent tissues.

PMID- 1399442
TI  - Factor analysis of dynamic magnetic resonance imaging in predicting the response
      of osteosarcoma to chemotherapy.
AB  - RATIONALE AND OBJECTIVES: The response of osteosarcoma to preoperative
      chemotherapy was assessed using dynamic magnetic resonance imaging (MRI)
      processed by factor analysis of medical image sequences (FAMIS). METHODS: Forty
      nine dynamic image sequences, acquired after a bolus injection of gadolinium in
      10 patients, were processed by FAMIS: FAMIS is a means whereby physiologic
      contrast enhancement kinetics, called factors, and their spatial distribution,
      termed factor images, are estimated. Tumor volumes were measured on static MRIs,
      and factor images were compared with histologic maps of the resected specimens.
      RESULTS: A substantial increase in tumor volume reflected a poor response to
      chemotherapy. Viable tumor was precisely depicted by the early vascular factor
      image, reflecting rapid uptake by tumor vessels. This early uptake disappeared in
      all five patients who responded to chemotherapy, whereas it persisted in four of
      five nonresponders. CONCLUSION: FAMIS of dynamic MRI is proposed as a possible
      means of predicting the response of osteosarcoma to chemotherapy.

PMID- 1399443
TI  - Magnetic resonance image synthesis from analytic solutions of spin-echo and radio
      frequency-spoiled gradient-echo images.
AB  - RATIONALE AND OBJECTIVES: To synthesize magnetic resonance images (MRI) in real
      time using a minimal data set obtained with routine clinical protocols and stored
      in a picture archiving and communication system (PACS) database. METHODS:
      Analytic solutions for T1 and T2 were obtained from a double and a single spin
      echo set, with routine parameters. Analytic solutions from radio frequency
      spoiled gradient-echo images, with TRs as low as 33 mseconds, also were used to
      synthesize gradient-echo images. RESULTS: Phantom studies showed that the errors
      in the synthesized images were significantly smaller than the errors in the T1-
      and T2-calculated images and similar to the source images. The gradient-echo
      images resulted in significant scan time savings. CONCLUSION: MRI synthesis from
      analytic solutions of T1, T2, and rho saves computational time and yields
      accurate values for the intrinsic parameters while allowing the use of routine
      clinical protocols. The availability of clinical images in the PACS database and
      the ability to synthesize images in real-time has allowed the development of a
      practical interactive teaching module.

PMID- 1399444
TI  - Proton (fat/water) chemical shift imaging in medical magnetic resonance imaging.
      Current status.
AB  - Fat/water CSI has recently been transformed from an experimental method to a
      routine clinical MRI approach, particularly for evaluating paramagnetic contrast
      enhancement in fat-rich regions and as a piggyback method for decreasing MRI
      artifacts, such as in MR angiographic and echo-planar imaging. The full and
      appropriate use of CSI in medical MRI requires consideration of the factors and
      strategies outlined in this review. As the commercial implementation of fat/water
      CSI continues, we can expect further applications in clinical and experimental
      studies. For example, in imaging areas where MRI has been of limited efficacy,
      such as pancreas imaging, skin microimaging and vascular imaging, there are
      indications that these CSI methods may have practical importance. It seems
      reasonable to project that for high chemically specific detail, medical fat/water
      CSI will ultimately be supplanted by SI methods, and certainly by localized
      spectroscopy. The power of the fat/water CSI method remains its extremely high
      anatomic resolution, which cannot be achieved by current spectroscopy or SI
      methods. The fat/water CSI methods provide a means for clinically relevant MRI
      with more accurate and chemically specific information. Expansion of these
      methods into three-dimensional and fast imaging formats is already taking place
      at or near the commercial level. For example, the feasibility of combining echo
      planar imaging and CSI methods has already been demonstrated. Methods based on
      the phase-contrast techniques, such as susceptibility mapping and interferometry,
      are additional implementations that can provide detailed and more specific
      information in a high anatomic detail format.

PMID- 1399445
TI  - Student and faculty perceptions of interactive learning in the radiology
      clerkship.
AB  - RATIONALE AND OBJECTIVES: The objective of this research is to develop and
      evaluate medical students' perceptions of interactive learning techniques for
      teaching the role of radiology in medical diagnosis to senior medical students.
      METHODS: Students in a 4-week radiology clerkship were given specific learning
      objectives and tasks that enabled them to be actively involved in radiology.
      Students rotated through six specialty areas in small groups. Some areas used the
      interactive format, whereas others used the traditional observation method. In
      the interactive format, clinical faculty involved student groups in examining
      patients, checking histories, making clinical/radiologic correlations, and
      discussing cases. RESULTS: Students consistently rated the interactive rotations
      higher (4.6 on a 5-point scale) than the observer format (3.3). The faculty and
      residents found the interactive format to be manageable and conducive to
      learning. CONCLUSION: Involving students in appropriate decision making and
      problem solving has proven to be a preferred way to teach radiology to medical
      students.

PMID- 1399446
TI  - An aid to image interpretation and differential diagnosis.
AB  - RATIONALE AND OBJECTIVES: Proven case conference is a weekly 1-hour session
      designed to aid diagnostic radiology residents in their ability to interpret
      images and formulate differential diagnoses. This article provides a detailed
      description of the format of this conference and its use in evaluating resident
      performance. METHODS: The scores of all residents on the written portion of this
      conference over a 2-year period were compiled. Results were divided according to
      each residency class, and each resident was compared with the mean of his or her
      class and with previous performance. RESULTS: There was overall improvement of
      the group over the course of residency. All individual scores showed improvement
      during the 2-year period studied. CONCLUSION: Proven case conference is a simply
      performed, well-accepted aid to image interpretation and differential diagnosis.
      It affords residents an ongoing opportunity for practical learning and provides
      the residency program director with an objective tool for resident evaluation.

PMID- 1399447
TI  - Image reconstruction of the interior of bodies that diffuse radiation.

PMID- 1399448
TI  - An artificial neural network for lesion detection on single-photon emission
      computed tomographic images.
AB  - RATIONALE AND OBJECTIVES: An artificial neural network (ANN) has been developed
      to detect nonactive circular lesions on single-slice, single-photon emission
      computed tomographic (SPECT) images reconstructed using filtered back projection
      (FBP). METHODS: The neural network is a single-layer perception which learns to
      identify features on the SPECT image using supervised training with a modified
      delta rule. The network was trained on a set of SPECT images containing
      clinically realistic levels of noise. The trained network was applied to a set of
      120 images, and the detection performance was evaluated at several decision
      thresholds using receiver operating characteristic (ROC) analysis. RESULTS: The
      trained neural network performed better than human observers for the same
      detection task with the same images as reflected by a significantly larger ROC
      curve area. CONCLUSIONS: ANN can be trained successfully to perform lesion
      detection on reconstructed SPECT images.

PMID- 1399449
TI  - T1 in subacute and chronic brain infarctions. Time-dependent development.
AB  - RATIONALE AND OBJECTIVES: Time-dependent behavior of T1 in brain infarcts and in
      brain tissue of the contralateral hemisphere was studied in the subacute and
      early chronic stages of stroke. METHODS: T1 was measured from magnetic resonance
      images (MRIs) of 29 patients as a function of infarct location and age. Another
      group of 11 patients was studied with consecutive MRI studies during the first 5
      weeks after the onset of infarct, and the distribution of T1 in the infarctions
      was analyzed from T1 maps using a histographic method. RESULTS: During the first
      2 months after a stroke, T1 was longer in the infarcted gray matter than in the
      infarcted white matter (P = .002), and prolonged linearly in both. The
      histographic analysis showed a component arising from tissue breakdown products
      that could be identified for up to 5 weeks. A transient lengthening in T1 of the
      contralateral hemisphere, reaching a maximum at 3 weeks, also was observed.
      CONCLUSIONS: These characteristics of recent infarctions differentiate them from
      older, gliotic lesions. The lengthening of T1 in the contralateral hemisphere may
      reflect remote flow and metabolic effects of brain infarctions.

PMID- 1399450
TI  - Magnetic resonance evaluation of regional left ventricular function. Effect of
      through-plane motion.
AB  - RATIONALE AND OBJECTIVES: Measurements of segmental contraction of the left
      ventricle by standard magnetic resonance imaging (MRI) and two-dimensional
      echocardiography involve the comparison of diastolic and systolic time frames
      acquired from the same imaging plane in space. As the cone-shaped left ventricle
      shortens along its long axis during systole, the observed contraction may differ
      from the true myocardial contraction. METHODS: Spin-echo MRI examinations in 21
      healthy subjects were performed to evaluate the error caused by failing to
      compensate for through-plane motion. RESULTS: The authors found that at the base
      and the mid-ventricle the observed contraction systematically underestimates true
      contraction by an average of 16% and 21%, respectively (P less than .001). At the
      apex, the segmental contraction may be overestimated or underestimated.
      CONCLUSIONS: Because of this error, standard MRI and echocardiography are less
      suited for basic research on cardiac contraction patterns. However, standard
      imaging techniques are valuable in clinical studies comparing groups of patients,
      because all measurements will suffer from the same systematic error.

PMID- 1399451
TI  - The anticoagulant effects of ionic and nonionic low-osmolar contrast media in
      dogs.
AB  - RATIONALE AND OBJECTIVES: The anticoagulant effects of ionic and nonionic low
      osmolar contrast media were evaluated in vivo. METHODS: The amount of clot
      deposited on guide wires placed in the femoral vessels of dogs was weighed 30
      minutes after the injection of 2 mL/kg of different contrast media. Six dogs were
      examined after injection of ioxaglate (ioxaglate group), six after injection of
      iopamidol (iopamidol group), and five after injection of saline (saline group).
      RESULTS: The mean weights of clot deposited on the guide wires in dogs in the
      ioxaglate group, the iopamidol group, and saline group were 30.5, 63.1, and 74.2
      mg, respectively. The mean weight of clot deposition on the guide wires in the
      ioxaglate group was significantly less than in the iopamidol and saline groups,
      whereas there was no statistical difference in the mean weight of clot deposition
      on the guide wires in the iopamidol and saline groups. CONCLUSIONS: Ioxaglate, a
      low-osmolar, ionic contrast medium, has a greater anticoagulant effect than a low
      osmolar, nonionic contrast agent, such as iopamidol.

PMID- 1399452
TI  - Magnetic resonance imaging, microangiography, and histology in a rat model of
      primary liver cancer.
AB  - RATIONALE AND OBJECTIVES: N-nitrosodiethylamine is able to induce various benign
      and malignant liver lesions in rats with a high success rate and a low mortality
      rate. It provides a more appropriate model that better simulates the various
      lesions occurring in patients than the usual model of tumor implantations.
      METHODS: Hepatic carcinogenesis was induced in 58 Wistar rats using oral N
      nitrosodiethylamine. The rats subsequently were studied by liver magnetic
      resonance imaging (MRI), postmortem microangiography, and histologic examination.
      RESULTS: Hepatic tumors developed in 57 rats. A wide variety of the tumors in the
      degree of vascularization, the type of vessels, the areas of intratumoral
      secretion and necrosis, and the tumor cell differentiation resulted from the
      tumor model. The authors were able to assess the contribution of the vascular,
      extravascular, and cellular components in the final pattern of contrast
      enhancement in MRI. CONCLUSIONS: The N-nitrosoethylamine model for hepatic tumor
      induction is simple, and provides a more representative range of tumors for
      experimental evaluation.

PMID- 1399453
TI  - Computed tomographic enhancement of the liver, liver abscesses, spleen, and major
      vessels with perfluorooctylbromide emulsion. Influence of dosage and injection
      velocity in an animal model.
AB  - RATIONALE AND OBJECTIVES: Computed tomographic (CT) enhancement of the liver,
      liver abscess, spleen, and major vessels was investigated between 2 and 48 hours
      after intravenous administration of perfluorooctylbromide (PFOB emulsion) in an
      animal model of 63 rabbits. METHODS: Twenty-one animals received 3 g/kg PFOB as a
      fast bolus injection. Using a slow infusion rate, the same number of animals
      received either the same dose (3 g/kg) or half the dose (1.5 g/kg). RESULTS:
      Vascular enhancement was best after bolus injection of 3 g/kg emulsion. The
      density peak occurred after 2 hours. A continuous enhancement of approximately
      100 Hounsfield units (HU) was observed up to 24 hours in the animals receiving 3
      g/kg, independent of the injection velocity. A density peak of 70 HU was found 2
      hours after the infusion of 1.5 g/kg. The density peak of the liver, the spleen,
      and the abscess wall was observed 48 hours after emulsion administration in all
      groups receiving 3 g/kg. The peak was approximately 150 HU for the liver, 400 HU
      for the spleen, and 150 HU for the abscess wall. In animals receiving only 1.5
      g/kg perflubron, the peak density of the abscess wall was 132 HU after 12 hours,
      approximately 80 HU for the liver between 2 and 48 hours, and approximately 280
      HU after 48 hours for the spleen. CONCLUSIONS: PFOB emulsion produces the highest
      vascular enhancement within the first 2 hours after the bolus injection of 3
      g/kg. For spleen and abscess wall imaging, even the relatively low dose of 1.5
      g/kg produced a satisfactory enhancement level for a significant length of time,
      whereas liver enhancement was best after administration of the higher dose.

PMID- 1399454
TI  - Quantitative evaluation of sialograms.
AB  - RATIONALE AND OBJECTIVES: The authors developed and evaluated a quantitative
      analytic method for interpreting clinical sialograms. METHODS: Images were
      obtained by digital subtraction sialography and transformed into binary form. The
      duct width of the image was calculated and represented as a normalized histogram.
      The effects of the volume of contrast medium injected and of the inclination
      angle of the objects on the histogram were examined. RESULTS: In model studies,
      the normalized histogram was affected insignificantly by these factors. Clinical
      sialograms of 18 patients with normal results, 12 patients with parotitis, and 5
      patients with Sjogren syndrome were preliminarily analyzed by the histogram
      method and four representative parameters of the histogram. Discriminant analysis
      showed a relatively high correct-predictive rate in the distinction between
      patients with normal and abnormal results. CONCLUSIONS: This method reduces the
      effect of observer variation in diagnosing sialograms, and improves diagnostic
      accuracy for assessing the presence of inflammatory diseases of the parotid
      gland.

PMID- 1399455
TI  - Vertebral body fractures in child abuse. Radiologic-histopathologic correlates.
AB  - RATIONALE AND OBJECTIVES: Vertebral injuries are rarely reported sequelae of
      child abuse, and little is known concerning the mechanisms of injury and healing.
      A preliminary investigation of these issues included correlating radiologic and
      histologic findings in children with vertebral injuries who died of complications
      relating to physical abuse. METHODS: Ten vertebral body fractures from four
      abused infants and young children were studied radiologically and
      histopathologically. RESULTS: Infants ranged in age from 7 to 36 months (mean, 21
      months). Three patients died of associated head injuries. One child died after
      abandonment. There were three pure vertebral body compression fractures, two
      superior end-plate fractures without compression deformity, and five
      anterosuperior end-plate fractures with associated compression deformity.
      Vertebral compression was generally mild (less than 25%). Typically, end-plate
      injuries were manifest histologically by extension of the fracture through the
      medullary trabeculae into the proliferative zone of the superior end plate. The
      resultant pattern was analogous to that described in a previous study, and could
      potentially result in a growth disturbance at the vertebral end plate.
      CONCLUSIONS: Observed radiologic patterns and histologic correlates may help
      explain previously described findings, such as vertebral notching, in abused
      infants.

PMID- 1399456
TI  - Receiver operating characteristic rating analysis. Generalization to the
      population of readers and patients with the jackknife method.

PMID- 1399457
TI  - Evaluation of a digital workstation for interpreting neonatal examinations. A
      receiver operating characteristic study.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to compare the diagnostic
      accuracy of interpreting clinical neonatal radiographs using a commercially
      available digital workstation versus conventional radiographic images. METHODS:
      The case sample consists of 100 chest or abdominal radiographs from the neonatal
      intensive care unit in which diagnosis was confirmed. Four radiologists served as
      observers. During two initial reading sessions, half of the studies were viewed
      on digital radiography monitors and the other half by plain film. Observers
      indicated whether each patient had normal or abnormal findings and their degree
      of confidence in this judgment. Six weeks later, observers viewed cases on the
      alternate presentation system. Two statistical analyses were performed: the data
      from each observer were treated as a separate experiment in the first analysis;
      the data from all observers were combined using a new method in the second
      analysis. RESULTS: No differences between areas under receiver operating
      characteristic (ROC) curves for viewing on the picture archiving and
      communication system (PACS) console and plain film were found for any observer
      (0.86 versus 0.86, 0.89 versus 0.86, 0.88 versus 0.85, 0.83 versus 0.82).
      CONCLUSIONS: The study suggests that for pediatric plain film images, video
      images offer diagnostic information comparable with that of conventional
      radiographs for neonatal examinations.

PMID- 1399458
TI  - Modeling approaches for the analysis of observer agreement.

PMID- 1399459
TI  - Retroperitoneal mass and anemia in an adolescent.

PMID- 1399460
TI  - A resident's perspective on the Introduction to Research Program (or ... how I
      spent one heck of a week in Chicago).

PMID- 1399461
TI  - An organizer's perspective to the Introduction to Research Program (or how a cold
      week in Chicago can be made most worthwhile).

PMID- 1399462
TI  - Medical coverage for the Iowa Games, 1987-1990.
AB  - The author summarizes the experience of the medical staff of the Iowa Games
      competition from 1987-90. The rate of injuries decreased each year, perhaps
      because of the increased conditioning and experience of the athletes.

PMID- 1399463
TI  - Patient confidentiality.

PMID- 1399464
TI  - Management consultants and the group practice.

PMID- 1399465
TI  - Victims of family violence are everywhere, say Iowa experts.
AB  - Family violence has become such a pervasive problem that every physician must be
      educated on how to diagnose and assist its victims. Iowa experts discuss family
      violence, particularly child abuse and elderly abuse.

PMID- 1399466
TI  - Gun control: Iowa physicians have opposing views.

PMID- 1399467
TI  - AMA fights back.
AB  - The vice chairman of the AMA Board fo trustees discusses the AMA's renewed
      campaign against family violence, including release of protocols for primary care
      physicians and formation of the Physicians Coalition Against Family Violence.

PMID- 1399468
TI  - Thoughts on spelling and writing.

PMID- 1399470
TI  - Combined meeting of the Association of Surgeons of Great Britain and Ireland and
      Trinity College Dublin, Medical School. Ireland, 20-23 September 1992. Abstracts.

PMID- 1399469
TI  - A vital link for physicians, staff.

PMID- 1399471
TI  - The use of baseline investigations in patients admitted from an accident and
      emergency department.
AB  - We studied the use of four investigations on patients admitted from our Accident
      and Emergency Department: full blood count, urea and electrolytes, chest x-ray
      and electrocardiogram. We found 1) that these investigations were performed on a
      high proportion of patients admitted 2) that a high percentage of these
      investigations yielded normal results. We suggest that a greater emphasis should
      be placed on clinical assessment, rather than the 'routine' use of
      investigations.

PMID- 1399472
TI  - Phlebotomy practices/needles stick injuries/hepatitis B status/among interns in a
      Dublin hospital.
AB  - Needlestick injury is the most important risk event for human immunodeficiency
      virus (HIV) and hepatitis B Virus (HBV) transmission to health-care workers. We
      examined phlebotomy practices, the frequency of needle stick injuries, the
      reporting of such injuries and hepatitis B status among interns in St James's
      Hospital during a six month period. This study took the form of a questionnaire.
      The response rate was 100%. 72% had at least one needlestick injury during this
      time period, 23% had injuries from known HIV sero-positive or hepatitis B surface
      antigen positive patients, less than 5% of all injuries were reported and only
      41% of interns were definitely hepatitis B immune. The majority (77%) resheated
      needles by hand.

PMID- 1399473
TI  - Communication skills training in undergraduate medicine: attitudes and attitude
      change.
AB  - The importance of communication skills training in undergraduate medical
      education is now widely accepted. However little is known about student attitudes
      towards their own communication skills and whether their attitudes changes as a
      result of participating in communication skills courses. The aim of the present
      study was to identify these attitudes prior to commencing such a course and to
      further evaluate changes in these attitudes on completion of the course. Results
      demonstrated an improvement in perceived confidence regarding a number of
      specific communication skills. The study provides further evidence of the value
      of such courses in undergraduate medical training.

PMID- 1399474
TI  - Continuous ambulatory peritoneal dialysis in children.
AB  - Fifteen children with end-stage renal failure (ESRF) were treated with continuous
      ambulatory peritoneal dialysis (CAPD) in the Children's Hospital Temple Street
      Dublin between July 1984 and December 1988. These fifteen children had 150.5
      treatment months, an average of 10.03 treatment months for each child. The
      children grew well during CAPD at an average of 0.59 cm per month. Blood pressure
      control was satisfactory with five out of 15 children requiring antihypertensive
      treatment during CAPD. The main complications of CAPD were peritonitis and
      catheter related problems. These 15 children experienced 47 episodes of
      peritonitis during 150.5 treatment months on CAPD with an average of one episode
      every 3.2 treatment months. Two of these children had a very high frequency of
      peritonitis (16 and 13 episodes each). If we exclude them from analysis, the
      remaining 13 children had frequency of one episode every 5.7 treatment months.
      During 150.5 treatment months, ten children required catheter replacement that is
      one catheter every 15 treatment months. One child died of candida peritonitis and
      to date twelve have proceeded to renal transplantation.

PMID- 1399476
TI  - Passive smoking and hearing loss in infants.
AB  - A cohort of infants scheduled to attend the 10 month developmental assessment
      were studied to determine whether hearing deficits are more common in those
      exposed to cigarette smoke. Hearing was assessed by the standard distraction test
      and those with persistent abnormalities were referred to a medical audiologist.
      Overall 77% of infants were exposed to cigarette smoke and 40% failed the initial
      hearing tests. Exposure to cigarette smoke was associated with a 4.9 times
      increase in the prevalence of hearing deficits and 75% of the cases of hearing
      loss were statistically attributable to exposure to cigarette smoke. The results
      of this study lend further weight to the hypothesis that exposure to cigarette
      smoke is a cause of hearing deficits in children.

PMID- 1399477
TI  - Consultation liaison psychiatry within the general hospital: referral pattern and
      management.
AB  - The emergence of consultation psychiatry as an important psychiatric subspecialty
      is in part due to the siting of psychiatric units in general hospitals, the
      manifest advances in medical technology and the increasing elderly population
      needing specialist care. This paper describes an evaluation of all referrals to a
      liaison psychiatry unit in a 550 bed general hospital over a six month period.
      205 requests for psychiatric consultation were received, which represented 2% of
      all admissions. There was considerable variation between departments with regard
      to the referral rate. Management most often consisted of advice, with over 50% of
      patients being subsequently referred for ongoing psychiatric care.

PMID- 1399475
TI  - Home intravenous therapy using a silastic long line catheter in cystic fibrosis
      patients.
AB  - Young patients with cystic fibrosis are now accustomed to having regular periods
      of intravenous therapy to help in the management of their recurring respiratory
      infections particularly due to pseudomonas organisms. Most patients will
      eventually experience difficulties in accepting recurring intravenous
      cannulations and the life span of the conventional intravenous cannula is
      frequently brief. We have compared percutaneous long line silastic catheters with
      conventional intravenous cannulas as intravenous access in children with cystic
      fibrosis being treated for pulmonary exacerbations. We conclude that silastic
      long lines are superior to conventional cannulas in terms of patient tolerance,
      reduction in the number of hospital admissions, reduction in the number of repeat
      venepunctures/cannulations and reduction in local complications. The high degree
      of patient acceptability has been impressive and has increased with the
      enthusiasm of children with cystic fibrosis for more frequent intravenous
      therapy.

PMID- 1399478
TI  - Herpes zoster oticus-diagnosis and treatment.
AB  - Four cases of Herpes Zoster Oticus (HZO) with facial paralysis are presented. HZO
      is a Herpes Zoster viral infection of the Geniculate Ganglion of the facial
      nerve. It presents classically with severe otalgia, a vesicular rash in the
      Concha or on the Pinna of the affected ear in association with a lower motor
      neurone lesion of the homolateral facial nerve. There also may be labyrinthine
      symptoms, sensineural hearing loss and vesicular eruptions in the regions
      supplied by the vagus and glossopharyngeal nerves viz, hypopharynx and oropharynx
      as these nerves communicate with the facial nerve. Treatment consists of
      Acyclovir. One reference in the past refers to a clustering of the condition and
      its predisposition for females. Interestingly all cases presented were referred
      with incorrect diagnoses.

PMID- 1399479
TI  - Asymptomatic abdominal aortic aneurysm.

PMID- 1399480
TI  - Comparison of the ease of handling of four different drug dispenser types in
      rheumatoid arthritis.

PMID- 1399481
TI  - Changes in blood pressure after stay at healthfarm.

PMID- 1399483
TI  - Parent held records an evaluation.

PMID- 1399482
TI  - Delayed diagnosis of a femoral neck fracture.

PMID- 1399484
TI  - Incidence of childhood-onset insulin-dependent diabetes mellitus.

PMID- 1399485
TI  - Salmeterol, a long acting bronchodilator, in the treatment of asthma.

PMID- 1399486
TI  - The changing face of malignant melanoma.

PMID- 1399487
TI  - Whiplash syndrome.

PMID- 1399488
TI  - Modern approach to the poorly grown fetus.

PMID- 1399489
TI  - Palpating enlarged kidneys.

PMID- 1399490
TI  - Committal procedures in Ireland.
AB  - The study aims to describe current committal practice in an Irish public
      psychiatric service and to establish the role of 'dangerousness' in determining
      practice. A six month retrospective review was undertaken using casenotes and
      original temporary forms of all patients committed to St Brendan's Hospital,
      Dublin within a six month period in 1990. A total of 136 cases were examined. In
      65% of cases the application for detention was initiated by a spouse or relative.
      The recommending physician was identified as a General Practitioner in 80% of
      cases, although most were locum GP's. The number of male and female patients were
      almost equal. There was a wide age range with the largest group (42%) in the
      range 26-40 years. Previous contact with the psychiatric service was found in 89%
      of cases. There was a wide range of diagnoses with the largest category (56%)
      suffering from schizophrenia. Of those not admitted with alcohol or drug related
      illness 66% showed evidence of acute psychotic symptoms. Length of admission was
      relatively short with 84% of patients being discharged within three months. A
      total of 43% showed evidence of being a danger to themselves or others.
      Significant differences were found between these patients and the non-dangerous
      group, the latter being more likely to be older and to suffer from a major
      psychotic illness. These findings indicate that a committal law based purely on
      'dangerousness' criteria would be likely to significantly affect committal
      practice in Ireland. These findings are discussed in relation to proposed changes
      in mental health legislation in Ireland.

PMID- 1399491
TI  - Awareness of heart attack signals and cardiac risk markers amongst the general
      public in Dublin.
AB  - Following myocardial infarction, early access to medical care is essential. In
      order to assess the ability to recognise and manage heart attack and its risk
      factors, 302 members of the public were surveyed. A surprisingly comprehensive
      knowledge base was revealed, together with apparently appropriate ideas about the
      management of myocardial infarction and its risk factors. The significance of
      this finding is discussed in the light of the well documented delays by members
      of the public in summoning help when they suspect heart attack.

PMID- 1399492
TI  - Intrapartum asphyxia in term and post term infants.
AB  - Many attempts have been made to identify infants at risk of suffering asphyxial
      brain damage. In a retrospective review of records at the Rotunda Hospital over a
      five year period all infants who died or suffered seizures, presumed secondary to
      asphyxia, were compared with the general hospital population. Out of 28,655
      deliveries reviewed, there were 13 deaths in infants at or after term associated
      with perinatal asphyxia, and 32 surviving infants had asphyxial seizures.
      Seizures were regarded as asphyxial in origin if they occurred in the first forty
      eight hours of life and were associated with other clinical evidence of asphyxia.
      The incidence of abnormal presentations, assisted breech deliveries, instrumental
      deliveries and emergency caesarean sections was all increased in the asphyxial
      categories compared to the control population. Referral to the fetal assessment
      unit was associated with a seizure rate of 0.16/1000 live births compared with a
      rate of 1.4/1000 in the remaining non referred hospital population. Nineteen
      percent of the infants who seized subsequently developed cerebral palsy. It would
      appear from our data that referral to the fetal assessment unit and the
      consequent assignment to "high risk" status is associated with low risk in terms
      of asphyxial outcome.

PMID- 1399493
TI  - "Rational" suicide and people with terminal conditions or disabilities.

PMID- 1399494
TI  - Life-prolonging and life-terminating treatment of severely handicapped newborn
      babies: a discussion of the Report of the Royal Dutch Society of Medicine on
      "Life-Terminating Actions with Incompetent Patients: Part I: Severely Handicapped
      Newborns".

PMID- 1399495
TI  - The role of the clear and convincing standard of proof in right to die cases.

PMID- 1399496
TI  - Cruzan and the demands of due process.

PMID- 1399497
TI  - Permitting the destruction of unworthy life. Its extent and form.

PMID- 1399498
TI  - Effect of nisoldipine on ambulatory blood pressure under 24-hour noninvasive
      monitoring.
AB  - The antihypertensive effect of nisoldipine on ambulatory blood pressure was
      investigated using continuous noninvasive monitoring in 12 patients with moderate
      essential hypertension. Treatment with nisoldipine 5 mg twice a day for 2 weeks
      resulted in a decrease in the average of each patient's mean arterial pressure
      for the whole day from 110.3 +/- 6.8 to 103.2 +/- 8.8 mm Hg (P = 0.0007). This
      decrease in mean arterial pressure was due to a decrease in both systolic and
      diastolic pressures. The reduction in blood pressure was most marked at the time
      of the originally high blood pressure readings. Comparisons of consecutive means
      of 2-hourly mean arterial pressure readings showed a statistically significant
      effect from 6:00 AM to midnight. Blood pressures between midnight and 6:00 AM
      were similarly low, before and during nisoldipine therapy. There was no change in
      heart rate. Untoward symptoms were reported with similar frequency, and of
      similar severity, both before and during therapy. Nisoldipine 5 mg twice a day is
      an effective antihypertensive agent, reducing moderately elevated blood pressure
      in ambulatory, working patients with essential hypertension. At the dosage used,
      it had no demonstrable effect on heart rate and minimal, if any, side effects.

PMID- 1399499
TI  - Vitamin A loading--an indicator of post-prandial lipoprotein clearance in healthy
      and hypertriglyceridemic subjects.
AB  - To study post-prandial lipoprotein metabolism in normolipidemic and
      hypertriglyceridemic subjects, a vitamin A fat loading test was used. This method
      specifically labels dietary fat particles with retinyl palmitate (RP). Following
      RP concentrations, metabolic behavior of chylomicrons and chylomicron remnants
      were studied. In normal subjects, post-prandial lipoproteins were present for
      more than 10 h. Total RP increased rapidly between 1 and 4 h, peaked at 6 h and
      declined rapidly between 6 and 10 h. The chylomicron and chylomicron remnant
      fractions behaved differently, showing precursor product relationship. The
      hypertriglyceridemic patients demonstrated a very severe defect in chylomicron
      clearance. This fraction was 2.8-fold higher than in normal subjects, which was
      7,260 vs. 2,600 micrograms/l, respectively. The large magnitude and long duration
      of post-prandial lipemia in normal and hypertriglyceridemic patients support the
      hypothesis that these atherogenic particles may play a role in the development of
      coronary heart disease.

PMID- 1399500
TI  - Late presentation of Bochdalek hernia: our experience and review of the
      literature.
AB  - During the last 18 years, 81 patients were diagnosed in the Department of
      Pediatric Surgery, Rambam Medical Center, as having congenital diaphragmatic
      hernia, 11 of whom (13.5%) presented after the first 24 h of life. In this
      retrospective study we describe our experience with late presentation (beyond 8
      weeks after birth) of Bochdalek hernia in 5 of the 11 patients, and we review the
      literature.

PMID- 1399501
TI  - The quality assurance committee in a general hospital: its use in improvement of
      the medical record.
AB  - A twice-yearly audit of a sample of medical records from each department of a
      general hospital was initiated by a quality assurance committee and pursued for 8
      years. Missing entries that were considered obligatory for good medical
      performance of each service were identified, and the results (expressed as
      percent of missing entries of the total) were communicated in graphic form to the
      specific departments and the senior staff of the hospital. This approach led to
      an improvement in the medical records (decrease of missing entries), which may
      reflect a higher quality of medical care. Thus, a sequential audit of medical
      records by a quality assurance committee may constitute a simple and effective
      method of monitoring and improving physicians' knowledge and performance.

PMID- 1399502
TI  - Recent trends in drug utilization in Israel.
AB  - There has been a considerable increase in the rate of medicine expenditure and
      consumption in Israel in the latter half of the 1980s in dollar terms compared to
      the previous decade both in total and per capita expenditure. At constant
      medicine prices there has been only a slight increase, reaching an average 9.4%
      annual growth in per capita consumption in the latter half of the 1980s. From the
      late 1970s to the late 1980s Israel had one of the highest rates of growth in
      total expenditure and per capita consumption at constant prices compared to OECD
      countries (Organization for Economic Cooperation and Development). The driving
      forces behind the real growth in overall expenditure continue to be the
      introduction of new drugs and changes in drug therapy. However, mainly as a
      result of substantial quantitative growth in per capita consumption in the
      private pharmacy sector, there was a greater growth in this sector than in Kupat
      Holim Klalit (Medical Insurance Scheme of the General Federation of Labor). An
      attempt to break down the aggregate into private pharmacy and Kupat Holim Klalit,
      according to expenditure, prices and consumption, indicate that although the
      latter has a much lower per capita expenditure, the price adjusted per capita
      consumption is similar in both sectors. Price adjusted per capita consumption is
      well below that of France and Italy, and close to that of the USA, the UK, West
      Germany and Switzerland. These findings are briefly discussed in terms of
      demographic differences.

PMID- 1399503
TI  - Primary biliary cirrhosis: increasing problem, approaching solution.

PMID- 1399504
TI  - Drug utilization: national and international comparisons.

PMID- 1399505
TI  - High dose of histamine required for gastric acid secretion in the common African
      toad, Bufo regularis.

PMID- 1399506
TI  - Prevalence of antibodies against measles, mumps and rubella in Israeli young
      adults.

PMID- 1399507
TI  - Strongyloides stercoralis hyperinfection in Israel--a case report.

PMID- 1399508
TI  - Prevalence of Chlamydia psittaci infection among persons who work with birds.

PMID- 1399509
TI  - Quinidine-induced uveitis.

PMID- 1399510
TI  - Pulmonary metastases from carcinoma of the cervix.

PMID- 1399511
TI  - Comparative study of Klebsiella oxytoca and Klebsiella pneumoniae isolates in a
      general hospital.

PMID- 1399512
TI  - Coronary artery bypass surgery.

PMID- 1399513
TI  - Reduction of hospital costs and administration of prophylactic antibiotherapy in
      gynecological surgery.

PMID- 1399514
TI  - Negligence of activated charcoal due to lack of current information.

PMID- 1399515
TI  - Increase in frequency of serious group A streptococcal infections.

PMID- 1399516
TI  - Use of informed consent with therapeutic paradox.
AB  - Debate persists in the literature and among clinicians about the ethical
      appropriateness of paradoxical interventions. It has been suggested that informed
      consent with therapeutic paradox would alleviate ethical concerns of deception,
      manipulation, harm to the client, and withholding of information from the client
      in therapy. The purpose of this study was to explore health care consumer
      reactions to the benefits and risks of therapeutic paradox as stated in a consent
      for treatment form. The study explored the responses of 32 medical patients to a
      hypothetical consent for treatment form for therapeutic paradox. Data were
      collected in a brief semistructured interview after subjects read the
      hypothetical consent form. Utilizing a case study, the investigator then offered
      an example of a successful paradoxical intervention and additional subject
      comments were solicited. Content analysis of the responses was made. Health care
      consumers had mixed responses to the consent form. While the consent form served
      as an obstacle for some consumers, many were willing to sign the consent form and
      accept treatment even though they had internal reservations and questions.
      Appropriateness of the consent form format is discussed.

PMID- 1399517
TI  - Psychological adaptation of nurses post-disaster.
AB  - Disasters have the potential to cause major disruptions in lifeline services and
      family support systems. As caregivers, nurses are required to make difficult
      choices during national emergencies and may be at risk for experiencing
      psychological distress following a disaster. This study describes the responses
      of a group of nurses following Hurricane Hugo, and makes recommendations to
      minimize the stress placed on nurses working in a time of disaster.

PMID- 1399518
TI  - Stressors and coping in adolescents exposed to Hurricane Hugo.

PMID- 1399520
TI  - Noncompliance with medication regimens in severely and persistently mentally ill
      schizophrenic patients.
AB  - Medication noncompliance contributes significantly to recurrence of symptoms and
      readmission to the hospital of schizophrenic patients. The purpose of this study
      was to determine factors identified by patients, family members, and nurses for
      patients' noncompliance. The Health Belief Model provided a theoretical
      framework. The sample consisted of 11 triads with a noncompliant schizophrenic
      patient, a family member, and a primary nurse in each triad. A structured
      interview was developed to assess stated reasons for noncompliance and factors
      relating to the patient's illness, medication practices, stressors, life-style,
      and support systems. Results showed that many patients stated they did not need
      medication or needed less than the amount prescribed. Family members and nurses
      agreed that the majority of patients did not believe that they needed medication.
      When asked if they thought they had a mental illness, most patients denied that
      they were ill. Other stated reasons for noncompliance were drug/alcohol use, and,
      for one patient, medication side effects. Additional findings were patients' low
      self-esteem; lack of knowledge about medications; inability to identify stressors
      in patients' lives; inability to identify early symptoms of relapse; patients'
      need for support from families; and families' stress from patients' abusive,
      unpredictable behavior. Use of the Health Belief Model is appropriate to study
      noncompliance in mentally ill patients if perception of illness threat is
      assessed. Conclusions were that patients and families could benefit from more
      knowledge of schizophrenia and its treatment, more awareness of stressors and
      signs of relapse, and improved mutual problem solving. Studies are needed to
      assess the effects of patients' denial of illness, denial of need for medication,
      and self-image/self-esteem on medication noncompliance.

PMID- 1399519
TI  - The individual who is severely and persistently mentally ill: directions for
      research and practice.
AB  - Psychiatric mental health nursing has not invested time and resources in the care
      of those with severe and persistent mental illness. In this article, current
      nursing research is reviewed and practice/research directions are delineated in
      the following areas: acute and chronic manifestations of symptoms, behavioral
      manifestations related to institutionalization, responses to psychiatric
      disorders over time, the long-term effects of psychotropic medication on
      behavior, and the impact of physical illnesses on psychiatric disorders.
      Knowledge is sorely needed in all of these areas to improve the nursing care of
      those persons with severe and persistent mental illness.

PMID- 1399521
TI  - Relocation appraisal, functional independence, morale, and health of nursing home
      residents.
AB  - Relocation to a nursing home can be stressful and may result in mental and
      physical illness. Appraisal, or the meaning assigned to relocation, can influence
      relocation outcome. This study examined the relationships between appraisal of
      relocation and 30 nursing home residents' psychological and physical health,
      morale, functional independence, and demographic and situational factors,
      including age, gender, income, education, prior residence, participation in the
      decision to relocate, and preparation for the move. Positive, benign, and
      challenge appraisals were related to higher morale and functional independence.
      Threat appraisal was related to poorer psychological health and lower morale.
      Harm-loss appraisal was associated with lower morale and lower functional
      independence. Preparation for the move was related to higher positive appraisal,
      higher morale, functional independence, and lower harm-loss scores. Implications
      include the need to assess people's appraisal of relocation so as to plan
      strategies that prevent relocation stress.

PMID- 1399522
TI  - Group therapy for people with borderline personality disorder: interventions
      associated with positive outcomes.
AB  - Group psychotherapy is becoming a more prevalent treatment option for people with
      borderline personality disorder. Various types of group approaches have been
      discussed; however, data about specific interventions and their relationship to
      outcomes for subgroups of people with borderline personality disorder are
      lacking. The purpose of this study was to explicate the interventions used in a
      successful group therapy program developed for community mental health center
      clients with borderline personality disorder. Two independent raters used the
      Hill Counselor Verbal Response Category System-Revised to describe and categorize
      the therapists' verbal responses. Coding of eight videotaped sessions indicated
      that the therapists' level and type of verbal activity did not change over time.
      The most frequently utilized interventions across sessions were providing
      information and seeking information. These responses are indicative of a moderate
      and high degree of structure. The results suggest that clinicians must consider
      the unique needs of serious and persistently ill people with borderline
      personality disorder and plan group interventions accordingly.

PMID- 1399524
TI  - Knee arthroscopy in a case of ochronotic arthropathy.

PMID- 1399523
TI  - Living with dying: coping with HIV disease.
AB  - People diagnosed with HIV disease experience multiple and severe stressors;
      however, little is known about these stressors and coping among this population.
      This phenomenological study was undertaken to (1) gain an understanding of the
      informants' lived experiences of coping with HIV disease and (2) develop a
      disease-specific instrument to measure stress and coping. The study involved
      interviews with 36 people with HIV disease. The interviews were analyzed and
      synthesized to (1) derive the structure of the experience through
      phenomenological analysis and (2) identify stress and coping themes through
      content analysis. Only the findings from the phenomenological analysis are
      reported here. The structure of the lived experience of coping with HIV disease
      unfolds from the initial diagnosis of being HIV-seropositive through the
      diagnosis of AIDS to impending death. The processes involved in this structure
      were labeled Living with Dying, Fighting the Sickness, and Getting Worn Out.

PMID- 1399525
TI  - Extra-articular synovial chondromatosis. Description of a rare localization in
      the arm.
AB  - The author presents a rare instance of extra-articular chondromatosis located
      around the tendon of the long head of the biceps brachii. The tendon subsequently
      tore and retracted, resulting in the formation of numerous cartilaginous loose
      bodies which collected in a mid-brachial cavity communicating with the canal
      which had previously housed the tendon. The author comments on the peculiar
      mechanism of production of this rare case of synovial chondromatosis as well as
      possible interpretations.

PMID- 1399526
TI  - The role of magnetic resonance imaging in lumbar disc disease.
AB  - The authors analyze 30 cases of herniated lumbar disc, comparing the clinical
      features with the magnetic resonance images and the intraoperative findings. In
      10 cases it was possible to compare MRI with computerized tomography as well.
      This paper confirms, in agreement with the international literature, the great
      diagnostic value of this new imaging study. While MRI is non-invasive and does
      not expose the patient to ionizing radiation, it provides an amount of
      information that could previously be obtained only by combining CT with
      myelography and discography.

PMID- 1399527
TI  - MR imaging in the diagnosis of carpal tunnel syndrome.
AB  - Diagnosis of carpal tunnel syndrome (CTS) is usually made on the basis of
      clinical and electrophysiologic data. Other tests, however, such as ultrasound
      and CT, have enabled us to acquire additional information regarding the
      anatomical definition of the structures inside the carpal tunnel. The superior
      quality of MRIs soft-tissue definition led us to employ it in cases of median
      nerve compression at the wrist in order to determine its true diagnostic value.
      We compared the preoperative electrophysiologic and MRI findings in 23 cases of
      CTS which had undergone surgical decompression of the median nerve at the wrist.
      Exact correspondence with the intraoperative findings confirmed the reliability
      of the anatomical information provided by MRI, yet the same comparison revealed
      that correct "functional" information could be provided only by the
      electrophysiologic tests.

PMID- 1399528
TI  - Ledderhose's disease: case study with histologic and ultrastructural analysis.
AB  - Two cases of Ledderhose's disease (plantar fibromatosis) are described with
      emphasis on histologic features. This disorder has three histologic stages: in
      the first, or proliferative, stage, numerous fibroblasts associated with a small
      amount of collagen are observed; in the second, or active, stage, the cells are
      more mature and the collagen is more evident; in the third, or maturation, stage,
      the extracellular matrix is composed of dense bundles of collagen fibers with few
      fibroblasts. Ultrastructural analysis revealed filamentous aggregation of an
      unknown nature among the collagen fiber bundles. The authors discuss some
      clinical, physiological, and pathologic aspects of a disorder which is similar to
      Dupuytren's disease but does not involve retraction of the surrounding anatomical
      structures.

PMID- 1399529
TI  - False aneurysm of the anterior tibial artery in lower leg fractures treated with
      the Ilizarov external fixator. Case report.
AB  - A case of open segmental fracture of the right lower leg treated with an Ilizarov
      external fixator in emergency surgery is presented. Approximately two months
      after operation, swelling in the anterior compartment of the tibia and repeated
      episodes of bleeding from one of the Kirschner wire holes led the authors to
      perform an angiography, which revealed the presence of a false aneurysm of the
      anterior tibial artery. The intraoperative finding of a double lesion in the
      anterior tibial artery confirmed the iatrogenous nature of the injury.

PMID- 1399530
TI  - Surgical treatment of arthritic varus knee by tibial corticotomy and angular
      distraction with an external fixator.
AB  - The authors report their experience in surgical treatment of the arthritic varus
      knee. After a comparative study of the most commonly used osteotomy techniques,
      they describe the results of their first cases of metaphyseal tibial corticotomy
      and angular distraction using an external fixator (25 cases).

PMID- 1399531
TI  - Recurrent dislocation of patella: three kinds of surgical treatment.
AB  - The authors compare three surgical techniques for treatment of recurrent
      dislocation of patella. The best results, even in the correction of lateral
      patellar displacement, were achieved with proximal realignment, while the worst
      results occurred when lateral retinacular release was used alone. In distal
      realignment, the degree of correction necessary must be ascertained by thorough
      preoperative assessment of both patellar height and malalignment between femoral
      groove and tibial tubercle. If the medial retinacular structures are weakened, it
      may be necessary to perform proximal realignment. We believe that a single
      surgical option is insufficient, and that the best solution for each individual
      case should be chosen according to precise indications. The choices include
      proximal realignment, distal realignment, or a combination of both, while lateral
      release should always be used in combination with another technique.

PMID- 1399532
TI  - Rotation of a skin flap from the side of the finger to the volar surface in the
      treatment of Dupuytren's disease.
AB  - The authors illustrate the technique of rotation of a skin flap from the side of
      a finger in the treatment of severe Dupuytren's disease especially when localized
      in the fourth or fifth ray. The results in 20 cases with an average follow-up of
      8 months are evaluated, and the indications and advantages over other surgical
      techniques are stated.

PMID- 1399533
TI  - Surgical treatment of traumatic lesions of the middle and lower cervical spine
      with Roy-Camille plates.
AB  - The authors report their experience in surgical treatment of traumatic lesions of
      the middle and lower cervical spine using the Roy-Camille method, discussing in
      detail the mechanism of injury according to the previously reported
      classification as well as the surgical technique. Special mention is given to the
      treatment of separation fracture of the articular mass and the results achieved
      with the "en-tuile" plate. The authors conclude that the Roy-Camille method
      yields satisfactory short and long-term results provided that the indications are
      closely followed.

PMID- 1399534
TI  - Microdiscectomy in treatment of herniated lumbar disc.
AB  - The authors studied 122 patients who had undergone microsurgery for herniated
      lumbar disc or isolated nerve root canal stenosis. The patients were reviewed one
      month and three months after surgery and then returned for a final evaluation
      after an average of 1.4 years. Intraoperative or postoperative complications
      occurred in 13 cases and consisted of misdiagnosis (discovered intraoperatively)
      of the level of the herniated disc (7 cases), dural laceration (3 cases), and
      discitis (3 cases). Limited discectomy was performed in 16 cases and complete
      discectomy in the others. Two patients who had undergone limited discectomy
      experienced recurrence; this did not occur when complete discectomy was
      performed. Discitis occurred in patients who had undergone complete discectomy.
      Most of the patients who underwent operation for disc herniation at one lumbar
      level with no complications began walking within 24 hours, and 72% were
      discharged within 36 hours. Eighty-five percent of the patients had a
      satisfactory result one month after surgery, and 91% had a satisfactory result at
      the final follow-up. There was no significant difference between patients with
      protruded herniation and patients with sequestered herniation. In the patients
      with nerve root canal stenosis the proportion of satisfactory results was 72% at
      one month and 88% at the final follow-up. The main advantage of microsurgery is
      the full illumination of the operative field, and this technique is strongly
      indicated in cases of single-level herniated disc. Over the short-term,
      microdiscectomy achieves a higher proportion of satisfactory results, requires a
      shorter hospitalization period, and allows an earlier return to work than
      traditional surgery. However, no significant difference was found between
      microsurgery and traditional surgery over the long-term.

PMID- 1399535
TI  - Middle and long-term results of flexion osteotomy for avascular necrosis of the
      femoral head.
AB  - The authors present the results of 19 flexion osteotomies performed in cases of
      avascular necrosis of the femoral head and followed up after an average of 8 1/2
      years. Significant clinical improvement was achieved in 85% of the patients. The
      radiographic picture is not quite as positive, but only 26% of the patients
      developed severe degenerative arthritis. The authors therefore consider this
      technique to be a valid alternative to immediate prosthetic replacement in
      selected patients.

PMID- 1399536
TI  - Intra-articular osteoid osteoma.
AB  - The joint is a relatively rare localization for osteoid osteoma. The location of
      the tumor and the concomitant synovitis-explain the peculiarity of the clinical
      features, which makes differential diagnosis with inflammatory diseases of the
      joint difficult. The authors report the results of three cases of intra-articular
      osteoid osteoma in which it was possible to determine the levels of prostaglandin
      (PGE2) and prostacyclin (PGI2), which are synthesized by the tumoral tissue. The
      increased production of these substances, which can reach up to 70 times their
      production in normal tissue, explain both the character of the pain and the
      origin of the synovitis which is so commonly found in this kind of tumor. The
      results of this study confirm the ability of the neoplastic tissue to produce
      high quantities of mediators of inflammation and enable the authors to formulate
      a theory as to the pathogenesis of the concomitant reactive synovitis observed in
      cases of intra-articular osteoid osteoma.

PMID- 1399537
TI  - Stress analysis of the growing femur: effects of frontal axial deviation.
AB  - Both the pathogenesis and the evolution of lower limb deformity secondary to
      primitive axial deviation during the growth period are affected by biomechanical
      factors which direct the remaining skeletal growth along abnormal lines. This
      study, limited to the femur, aims to analyze these factors from a practical as
      well as abstract standpoint, with references to prevention and surgical
      treatment. For this biomechanical study the authors applied finite element
      analysis to 16 models of the femur with various deformities in the frontal plane-
      proximal, distal, valgus, and varus. Analysis of the results shows significant
      variations in the physiologic status of stress on the femur associated with axial
      deviation in the frontal plane. These variations have special characteristics
      according to the type and level of the deviation. Furthermore, the stress
      imbalances seem to be concentrated in the distal metaphyseal region, even in
      cases of proximal deformity.

PMID- 1399538
TI  - The effects of lengthening on nerves.
AB  - Use of external fixators in limb lengthening and skin expanders in plastic
      surgery are well-known operative techniques. In some cases neurologic
      complications arise due to distraction which is either excessive or too fast.
      What happens to the nerve in these cases has not yet been thoroughly
      investigated. We therefore conducted an experiment on the sciatic nerve of rats.
      In one group of animals the nerve was studied after lengthening the femur, and in
      the other group after lengthening the nerve itself with a skin expander.
      Electrophysiologic and histologic studies (optic microscopy and axon teasing)
      were used to examine the effects of tension on the sciatic nerve. The results
      suggest that if distraction is performed gradually, the nerve does not undergo
      any electrophysiologic functional changes. It does, however, undergo some
      morphologic changes, such as a decrease in both the areas of the axons and the
      myelin sheaths, an increase in the distances between the nodes, and proliferation
      of Schwann cells.

PMID- 1399539
TI  - Relationship between femoral neck fractures and osteoporosis in the elderly:
      densitometric analysis.
AB  - The authors report the findings of densitometric analysis performed on 25
      patients from of 70 to 90 years of age with fractures of the proximal femur.
      Although bone density decreased progressively with age, there was not a close
      correlation between bone density and fracture, as the latter occurred even when
      the densitometric values were relatively high for the patient's sex and age.

PMID- 1399540
TI  - Metabolic changes in bone in old age.
AB  - The authors conducted a study on the effect of aging upon the factors which
      regulate calcium metabolism. Hormonal and biochemical tests were performed on
      samples from patients selected on the basis of sex, age, and other
      characteristics in order to determine the trend of these regulatory factors in
      middle and old age, with particular attention to osteoporosis in women. The
      authors propose several theories regarding the pathogenetic mechanisms of
      osteoporosis on the basis of this study as well as the literature.

PMID- 1399541
TI  - Implementation of new managed care rules by our major insurance provider.

PMID- 1399542
TI  - Acute rheumatic fever in Hawaii: 1966 to 1988.
AB  - Seventy five children with acute rheumatic fever (ARF) were hospitalized on Oahu
      from 1984 to 1988. The annual incidence rate was 9.5 (all rates are per 100,000
      children per year). The first attack and recurrent attack rates were 7.9 and 1.6.
      Polyarthritis occurred in 84%, chorea in 7%, and carditis in 32%. Mitral
      insufficiency was the most common valvular lesion (88%). Hawaiians/part Hawaiians
      and Samoans had the highest incidence rates (relative risk 3 and 56,
      respectively). Polynesian children were 84 times more likely to develop carditis.
      Five hundred thirty nine ARF cases were hospitalized on Oahu, 1966 to 1974 and
      from 1976 to 1988. The annual incidence rate of ARF on Oahu has remained fairly
      constant at about 12.4. The incidence rates in all ethnic groups have decreased
      except in Samoan children.

PMID- 1399543
TI  - Health matters: social, economic and philosophical aspects of health care.

PMID- 1399544
TI  - Cardiopulmonary exercise: a recently discovered secret of tai chi.
AB  - Every piece of literature or book about tai chi claims it to be the supreme
      martial art (soft style) and a therapeutic exercise. Nevertheless, none of the
      authors can describe scientifically how and why it works. Many people did not
      gain any health benefit in practicing tai chi and only very few people were able
      to apply its legendary secret power. During the last 10 years, the author thought
      he had discovered the secret in Hong Kong and brought it to Los Angeles. The
      secret lies in the fundamental movements of the body, called tai chi basic
      exercise routines. The entry level of the exercise has many similarities with
      medical treatments for respiratory illness and with walking exercise--the most
      recommended aerobic exercise for coronary artery disease.

PMID- 1399545
TI  - Tuberculosis: a personal commentary.
AB  - Tuberculosis is another of those diseases from which our attention has been
      diverted in recent decades, and which may now come back to plague us. I refer to
      the timely warning in Dr Frankel's report and Dr Reppun's editorial comment in
      the Hawaii Medical Journal of December 1991.

PMID- 1399546
TI  - Childhood onset cluster headaches.
AB  - Cluster headaches are rare in childhood. We identified 35 patients with cluster
      headaches starting at or before 18 years of age, including 7 patients with onset
      prior to age 10. All patients met the criteria of the International Headache
      Society for episodic or chronic cluster headaches. Patients experienced cluster
      headaches for as long as 20 years before seeking medical attention and required
      many medical contacts to establish the correct diagnosis. The clinical features
      of cluster headaches during childhood were similar to those which typically occur
      in adult life. Cluster headache patterns changed over 18 years of follow up. The
      frequency and duration of cluster periods increased in 14 subjects. The frequency
      of single headache attacks during cluster periods also increased in a similar
      number of subjects. We conclude that cluster headaches starting in childhood or
      adolescence closely resemble the adult form of the disease. In many patients, the
      frequency and duration of cluster periods and the frequency of the individual
      headache episodes increased over time. Cluster headache represent a treatable
      under-recognized cause of severe headaches in childhood and adolescence.

PMID- 1399547
TI  - Naproxen sodium versus ergotamine tartrate in the treatment of acute migraine
      attacks.
AB  - A double-blind parallel study compared the efficacy and safety of naproxen sodium
      (NPX) and ergotamine tartrate (ERG) as abortive therapy for acute headache in 79
      patients with classical or common migraine. The design study was of the double
      blind design. Forty-two patients completed the study. Discontinuation of
      treatment was generally due to lack of efficacy or adverse reactions. NPX was
      significantly better than ERG in the overall efficacy of treatment rated by the
      patients (p less than 004). NPX was comparable to ERG in reducing the severity
      and duration of the headache and its associated symptoms. In classical migraine,
      NPX was better than ERG in alleviating the severity of headache. Patients in the
      NPX group tended to use less rescue medication. There was no significant
      difference in the frequency of side-effects reported by the patients under NPX or
      ERG. This study demonstrates that NPX is as safe as ERG, and somewhat more
      effective in acute migraine attacks (although the difference is not statistically
      significant) and that migrainous patients tend to prefer NPX to ERG in treating
      their acute migraine headaches.

PMID- 1399548
TI  - Fear of pain in recurrent headache sufferers.
AB  - We investigated the role of fear of pain in headache sufferers using the Fear of
      Pain Questionnaire (FPQ). Seventy-six headache sufferers and 58 controls
      completed the FPQ and measures of depression, anxiety, and anger. Headache
      sufferers also completed measures of stress-related physical symptoms and coping
      with pain. We found that the FPQ has excellent internal consistency as well as
      good concurrent and construct validity indicated by the high correlations between
      the FPQ subscales and both anxiety and depression but low correlations with
      anger. There were marked differences between headache sufferers and controls on
      the FPQ; headache sufferers showed much greater fear of severe and medical pain
      and lower fear of minor pain. Fear of pain was generally not related to headache
      characteristics such as frequency, severity, or duration. On the other hand, it
      was related to headache impact such as disruption of pleasurable activities.
      These results are consistent with models of chronic pain disorders which
      emphasize the role of fear of pain over the nociceptive intensity of the pain
      stimulus.

PMID- 1399549
TI  - The prevalence of cerebral damage varies with migraine type: a MRI study.
AB  - Studies on the prevalence of MRI signal abnormalities in the brains of
      migraineurs have yielded controversial results. In order to provide further data
      on this issue we reviewed the MRI scans of 38 migraine patients without current
      neurologic symptoms (mean age 35.8 +/- 11.9 years). In addition, we compared the
      findings in those 24 migraineurs under 50 years without major cerebrovascular
      risk factors (mean age 30.1 +/- 9.0 years) to that in 14 headache and risk factor
      free volunteers (mean age 37.8 +/- 5.3 years). Overall, focal areas of
      hyperintense signal were seen in 15 (39%) patients. They were present on both
      proton density and T2-weighted spin-echo sequences. Lesion prevalence varied
      according to the type of headache (18% in migraine without aura, 53% in migraine
      with typical aura, 38% in basilar migraine). The subset of migraine patients
      under 50 years exhibited MRI signal abnormalities more than twice as often as
      controls (33% vs. 14%). Punctate white matter hyperintensities were the
      predominant finding and were seen in 10 of 15 individuals with MRI lesions. More
      striking signal abnormalities consisted of symmetrical areas of hyperintensity
      lateral to the posterior horns in two 24 year old patients and of extensive white
      matter damage with lacunar infarcts in a 59 year old woman. Our findings confirm
      a higher prevalence of MRI lesions in a mixed group of migraineurs than in
      headache free individuals. Signal abnormalities are most often non-specific,
      however their occurrence relates to the type of migraine.

PMID- 1399550
TI  - The relationship of ovarian steroids, headache activity and menstrual distress: a
      pilot study with female migraineurs.
AB  - Fourteen female volunteers who met diagnostic criteria for migraine headache
      monitored their headache activity and menstrual distress symptoms for one
      menstrual cycle. Serum estradiol and progesterone levels, and menstrual distress
      measures were collected at four points of the menstrual cycle: menstrual,
      ovulatory, luteal and premenstrual. Results indicated that one patient (7.1%) had
      menstrual migraine, 10 patients (71.4%) had menstrually-related headache and 3
      (21.4%) had migraine headache unrelated to their menstrual cycle: subsequent
      analyses were conducted with the first two groups. Headache activity for the
      sample was highest during the premenstrual phase. Headache activity during the
      luteal and premenstrual phases was related to luteal phase progesterone levels.
      Menstrual distress was highest during the menstrual and premenstrual phases of
      the cycle, and these symptoms were related to higher estradiol levels, higher
      estradiol/progesterone ratios, and increased headache activity. These results
      indicated that for women with menstrual migraine or menstrually-related migraine,
      luteal progesterone and estradiol and the estradiol/progesterone ratio may be
      significantly related to menstrual distress during the premenstrual phase of the
      cycle. The estradiol/progesterone ratio was not more related to headache or
      menstrual distress than either of these ovarian hormones alone. Suggestions for
      future research in this area are offered.

PMID- 1399551
TI  - Flunarizine is effective in prophylaxis of headache associated with scleroderma.
AB  - Migraine-like headaches may occasionally be seen in patients with scleroderma.
      The mechanism of these headaches is not well established but may be secondary to
      central "Raynaud's phenomenon". We report a patient with such headaches that
      responded dramatically to the centrally acting calcium channel blocker,
      flunarizine. We suggest that flunarizine should be considered in the management
      of patients with scleroderma and migraine-like headaches.

PMID- 1399552
TI  - Migraine-associated dizziness.
AB  - We reviewed the clinical histories, examinations and results of quantitative
      vestibular testing in 91 patients with migraine-associated dizziness. Nausea and
      vomiting, hypersensitivity to motion and postural instability accompanied the
      dizziness. In the majority of patients, the temporal profile of the dizziness was
      more typical of the headache phase of migraine than of the aura phase. Nineteen
      patients (20.9%) had unilateral hypoexcitability to caloric stimulation, which
      represents a modestly increased risk of damage to the peripheral vestibular
      apparatus. We propose two separate pathophysiologic mechanisms for the production
      of dizziness with migraine: Short-duration vertiginous attacks lasting minutes to
      2 hours and temporally associated with headache are due to the same mechanism as
      other aura phenomena (spreading wave of depression and/or transient vasospasm).
      Longer-duration attacks of vertigo and motion sickness lasting days, with or
      without headache, result from the release of neuroactive peptides into peripheral
      and central vestibular structures, causing an increased baseline firing of
      primary afferent neurons and increased sensitivity to motion.

PMID- 1399554
TI  - Menstrual migraine.

PMID- 1399553
TI  - Handling of 5-hydroxytryptamine by platelets in migraine.
AB  - There is little dispute that a link exists between 5-hydroxytryptamine (5HT) and
      migraine but the exact mechanism of an attack has yet to be established. The
      handling of 5HT by the platelet is regarded as a simple model of the handling of
      5HT by nerve terminals. If differences are seen in how the platelets from
      migraineurs handle 5HT compared to those from a control population, it is
      possible that a similar difference exists in the nerve terminal. The
      Haemostatometer allows the rapid and simultaneous in vitro assessment of platelet
      function (shear-induced haemostasis), coagulation and thrombolysis from non
      anticoagulated blood samples. In this study, a baseline comparison of haemostasis
      was made on 20 migraineurs between attacks and 20 controls. No differences were
      found in the results from each of the two groups. 5 microM of 5HT was then added
      to blood taken from 10 migraineurs and 10 controls and the recordings were
      repeated. Again, no differences were found between the results from the two
      groups. In blood taken from both migraineurs and controls, the effect of 5HT was
      to significantly enhance clotting time and clot lysis. No effect was seen on
      primary aggregation. The possible reasons for and significance of these findings
      is discussed.

PMID- 1399555
TI  - Ritanserin is not effective in tension headache.

PMID- 1399556
TI  - Clomiphene and migraine.

PMID- 1399557
TI  - Tachyphylaxis in migraine prophylaxis.

PMID- 1399558
TI  - Short-lasting, unilateral, neuralgiform headache attacks with conjunctival
      injection and tearing (SUNCT syndrome): IV. Respiratory sinus arrhythmia during
      and outside paroxysms.
AB  - SUNCT is a headache syndrome characterized by short-lasting (usually 15-120 sec),
      unilateral head pain paroxysms localized in the peri-ocular area, accompanied by
      conjunctival injection, lacrimation, nasal stuffiness, rhinorrhea, and
      subclinical forehead sweating, all on the symptomatic side. A relative
      bradycardia seems to be an integral part of the paroxysm; a parasympathetic
      stimulation could theoretically be the causative factor for the bradycardia. In 3
      SUNCT patients, vagal nerve function (E:I ratio) has been monitored outside and
      during pain paroxysms, while 3 other patients could be studied in the attack-free
      period only. E:I ratio is obtainable in the course of a maximally deep breath and
      represents the ratio of the longest R-R interval during a 5 sec long expiration
      to the shortest R-R interval during a 5 sec long expiration. The mean E:I ratio
      of SUNCT patients outside paroxysms was significantly higher than the mean E:I
      ratio in an aged-matched control group. The E:I ratio was, however, significantly
      decreased during paroxysms in comparison with ratios obtained outside the pain
      paroxysms. After 0.6 mg atropine administration s.c. to one of the patients in
      the symptomatic phase, the heart rate increased, and the relative bradycardia
      during headache paroxysm was diminished (but not completely abolished). The E:I
      ratio was lowered but it was still slightly larger outside than during attacks.
      The reason for the abrupt and seemingly clear attack-related decrement in E:I
      ratio together with the previously described relative bradycardia remains
      enigmatic, however the possibility of increased parasympathetic tone cannot be
      excluded.

PMID- 1399559
TI  - SUNCT may be another manifestation of orbital venous vasculitis.
AB  - A patient with more than 20 years of SUNCT, i.e., long lasting periods with
      frequent attacks of intense orbital pain with a duration of about one minute,
      associated with ipsilateral conjunctival injection, lacrimation, rhinorrhea and
      facial sweating is described. Some attacks were possibly related to increased
      cerebral blood flow but could also be triggered from the oral area. Orbital
      phlebography showed pathologic changes on the side of the pain, changes which
      were normalized when these attacks ceased to appear. Due to these findings in
      conjunction with serum evidence of inflammation, associated systemic symptoms and
      susceptibility to steroids and azathioprine, venous vasculitis is suggested to be
      the cause of SUNCT in this patient. Carbamazepine and sumatriptan decreased the
      frequency, intensity and duration of attacks, although not completely.

PMID- 1399560
TI  - Low dose flunarizine in the prophylaxis of migraine.
AB  - In a period of one year (1990) we selected 40 patients suffering from migraine.
      For an open randomized study there were 2 groups of patients: the first were
      treated with 10mg of flunarizine per day and the second with 3 mg per day. The
      patients were treated for 4 months consecutively. There were 11 drop outs
      (27.5%): nine for poor compliance and 2 due to side effects. The efficacy of
      flunarizine in the prophylaxis of migraine was essentially identical in the two
      dosage groups while the incidence of side effects was considerably reduced in the
      patients treated with the lower dose.

PMID- 1399561
TI  - Non-pharmacological treatment of headache: is less more?
AB  - A twenty-six article review of the literature pertaining to non-pharmacological
      treatment of headache was undertaken. The data supports no significant difference
      in the efficacy of hypnosis, biofeedback and relaxation training. These studies
      demonstrated no relationship between hypnotizability or capacity for temperature
      elevation and headache improvement. The literature reviewed suggests the
      mechanism for improvement with non-pharmacological treatment may be
      physiologically nonspecific, with patient age, perceived locus of control and
      motivation likely to predict successful treatment. Home-based, minimal therapist
      contact, biofeedback and relaxation treatment appear to work as effectively as
      intensive clinic-based treatment.

PMID- 1399562
TI  - Evaluation and emergency treatment of headache.
AB  - Headache is a common complaint in patients presenting to the emergency
      department. Most such headaches are benign, but some have a more severe organic
      cause. Occasionally, patients present with a chronic headache disorder with which
      they can no longer cope. The new International Headache Society Classification of
      Headache is reviewed along with the differential diagnosis of benign headache
      disorders. Headache diagnosis by history is examined in detail followed by a
      discussion of the emergency presentation of headache patients. Causes for concern
      are presented, along with a detailed discussion of differential diagnosis,
      including subarachnoid hemorrhage, meningitis, sinusitis, glaucoma, internal
      carotid artery dissection, and cerebro-vascular disease. Also discussed are
      medications used for the symptomatic treatment of headache, including analgesics,
      NSAIDs, narcotics, and ergotamine preparations. Approaches to the treatment of
      the severe, persistent headache in the emergency department are outlined and
      treatment options suggested. Headache medication overuse is discussed and
      guidelines are presented to recognize the condition and prevent its recurrence.

PMID- 1399563
TI  - Orbital phlebography: a comparison between cluster headache and other headaches.
AB  - Orbital phlebography has previously been found to be pathologic in 8 of 13
      patients with episodic cluster headache. To compare the frequency and pattern of
      the pathologic findings in cluster headache with those in other headache
      categories, orbital phlebographies were carried out in patients with cluster
      headache, cervicogenic headache, migraine and tension-type headache (tension
      headache). The investigations were evaluated independently by two radiologists,
      one of whom had no knowledge of the diagnoses. The frequencies of pathologic
      findings were at maximal 2/12 in the cluster headache group, 2/11 in the
      cervicogenic headache group, 5/12 in the migraine group and 5/15 in the tension
      type headache group. The investigators agreed completely in the evaluation of
      39/50 phlebograms, with lesser disagreements in 7. In conclusion, the frequency
      of pathologic findings at orbital phlebography in cluster headache was not higher
      than in the other diagnostic categories investigated, and the pattern of the
      pathology was generally the same.

PMID- 1399564
TI  - Great auricular neuralgia.
AB  - An unusual neuralgia of the great auricular nerve resulting from a skin incision
      to insert a cardiac pacemaker is described. The anatomy and presumed
      pathophysiology are discussed.

PMID- 1399565
TI  - Selegeline, a MAO B inhibitor, is not effective in the prophylaxis of migraine
      without aura--an open study.

PMID- 1399566
TI  - Association between malignancies of the upper aerodigestive tract and uterine
      cervix.
AB  - Cancers of the cervix and buccal cavity share histologic, epidemiologic, and
      exposure characteristics. In particular, cigarette smoking and human
      papillomavirus (HPV) have been cited as etiologic cofactors of both malignancies.
      Using incidence data from the Surveillance, Epidemiology, and End Results (SEER)
      program of the National Cancer Institute for the years 1973 through 1984, we
      evaluated the incidence of second cancers of the buccal cavity following an
      initial cervical cancer. Standardized incidence ratios (SIR) were uniformly
      elevated for both white (SIR = 2.0), and black (SIR = 3.5) women. There were also
      elevated risks for the development of cervical cancer following an initial buccal
      cavity cancer (SIRs = 3.3 and 2.5, respectively). A similar pattern was evident
      for laryngeal cancer among white women. HPV transmission could account in part
      for the paired occurrence of these two anatomically distinct cancer sites.
      Cigarette smoking could act as a synergistic cofactor in the malignant
      transformation of viral genome-harboring tissue.

PMID- 1399567
TI  - Videofluoroscopy of the pharyngoesophageal segment during tracheoesophageal and
      esophageal speech.
AB  - The purpose of this preliminary investigation was to identify the location and
      length of the pharyngoesophageal (PE) segment during esophageal and
      tracheoesophageal (TE) speech among laryngectomees who were proficient in both
      methods of vocalization. Four patients who had undergone total laryngectomy and
      tracheoesophageal puncture served as subjects. Voice recordings were obtained and
      played to listeners of varying experience with laryngectomees. Videofluoroscopy
      was performed while the patients sustained "ah" in both modes of speech. Results
      of these analyses revealed that TE speech was rated as more effective than
      esophageal speech in all 4 subjects. However, only minimal differences were found
      in the length and the location of the PE segment during TE and esophageal speech
      when within subject comparisons were made. This study is the first to compare the
      physical characteristics of the PE segment during esophageal speech and TE speech
      as produced by the same speaker.

PMID- 1399568
TI  - Occult lymph node metastasis in small oral tongue cancers.
AB  - The need to treat the neck in patients with a small primary cancer in the tongue
      remains controversial. Twenty-eight patients with stage I or II oral tongue
      squamous carcinomas were retrospectively reviewed. They had not received previous
      treatment. The tongue primary was excised via the transoral route and the neck
      was observed closely during follow-up. Thirteen patients developed ipsilateral
      nodal metastases during follow-up, three of whom also had simultaneous recurrence
      at the primary site. An additional patient had recurrence at the primary site
      alone. The incidence of occult neck metastasis was 42% (10 of 24). No tumor
      related death occurred in the group without nodal metastasis. The salvage rate
      after appearance of nodal metastasis was 30%. In oral tongue cancers, elective
      neck treatment should be considered regardless of a small primary and negative
      neck examination because of the high incidence of occult nodal metastasis and the
      poor outcome after salvage treatment.

PMID- 1399569
TI  - Rapid superselective high-dose cisplatin infusion for advanced head and neck
      malignancies.
AB  - Advances in vascular radiology techniques for superselective arterial infusions
      and methods to overcome systemic toxicity from high-dose cisplatin chemotherapy
      encouraged us to reevaluate the effects of rapid regional cisplatin infusion for
      patients with head and neck malignancies. Twenty patients (17 carcinomas, three
      sarcomas) received high-dose cisplatin (100-200 mg/m2) by this method. Fifteen of
      the 17 patients with upper aerodigestive tract carcinoma are part of an ongoing
      phase I dose escalation of cisplatin with sodium thiosulfate neutralization.
      Three additional patients with sarcomas were treated with intra-arterial (IA)
      cisplatin and systemic Adriamycin. Fifty-three IA infusions were performed
      without any complications. Only minimal toxicity related to the chemotherapy was
      observed. The overall response rate for previously untreated patients was nine of
      10 (90%) [complete response (CR) 67%; partial response (PR) 33%]. The response
      rate for patients with recurrent disease was five of eight (63%) (CR 20%, PR
      80%). The average length of follow-up is 9.5 months and the actuarial survival
      rate is 56%. Superselective rapid infusion of high-dose cisplatin for patients
      with advanced head and neck malignancies is feasible, relatively nontoxic, and
      may have important applications in multimodality therapy, particularly for
      patients with bulky primary disease.

PMID- 1399570
TI  - Embolization of a life-threatening mandibular vascular malformation by direct
      percutaneous transmandibular puncture.
AB  - Vascular malformations of the mandible are uncommon, but often present with
      significant hemorrhage. Transarterial vessel occlusion has become a valuable
      primary or adjunctive treatment for such lesions, as well as for most other
      symptomatic congenital and acquired head and neck vascular anomalies. Permanent
      embolic obliteration of the malformation requires placement of occlusive material
      directly into the nidus (core) of the lesion. Prohibitively complex proximal
      vasculature may prevent successful catheter positioning and lead to failure of
      traditional embolotherapy. Even optimal placement of arterial embolic material
      may fail to fully obliterate the nidus, allowing eventual restoration of flow to
      the lesion due to arterial recanalization. Under such circumstances it may be
      possible to obliterate the malformation and control lesional hemorrhage by
      occlusion of the malformation or its venous drainage by direct percutaneous
      mandibular puncture. In our case, multiple transarterial embolizations failed to
      sufficiently manage a symptomatic vascular malformation. Successful embolotherapy
      was performed via direct puncture of the venous side of the malformation through
      the mandibular cortex. Venous thrombosis induced concomitant occlusion of
      abnormal arteriovenous shunts, resulting in long-term control of life-threatening
      oral hemorrhage.

PMID- 1399571
TI  - Surgical anatomy of the external branch of the superior laryngeal nerve.
AB  - Iatrogenic lesions of the external branch of the superior laryngeal nerve (EBSLN)
      during thyroidectomies are not infrequent due to the possibility of anatomic
      variations of the relationships of this nerve with the superior thyroid vessels.
      Therefore, based on an anatomic analysis of 30 superior thyroid poles from 15
      fresh cadavers, a new classification of the EBSLN was proposed, considering the
      jeopardy during a thyroidectomy. Thirty-seven percent of the nerves were type 2,
      ie, crossing the superior thyroid pedicle less than 1 cm above the superior
      thyroid pole. It is notable that 20% were type 2b, ie, crossing the vessels below
      the upper border of the pole, having been considered "high risk." This incidence
      was comparable with other series, which found dangerous anatomic variations of
      the EBSLN in the range of 15% to 68%, confirming that a significant proportion of
      these nerves might be at risk during surgery on the superior thyroid pole.

PMID- 1399572
TI  - Sarcoidosis masquerading as a parathyroid adenoma.
AB  - Two patients presented with a presumptive diagnosis of hyperparathyroidism.
      Surgically excised "parathyroid glands" were found to be, in fact, large lymph
      nodes with sarcoid granulomata. In one patient, the preoperative localization of
      the "parathyroid adenoma" was based on scintigraphy (thallium-technetium
      subtraction imaging) and sonography procedures. The differential diagnosis of
      hypercalcemia, and positive scintigraphy-sonography studies, must include
      sarcoidosis in an isolated cervical lymph nodes.

PMID- 1399573
TI  - Basaloid squamous carcinoma of the buccal cavity.
AB  - Basaloid-squamous carcinoma was first recognized as a separate pathologic entity
      in 1986. It has been described in the hypopharynx, larynx, base of tongue, and
      nasal cavity. We report the first case of this rare tumor occurring in the buccal
      cavity and review the atypical squamous cell carcinomas that occurred in these
      sites.

PMID- 1399574
TI  - Curative irradiation of the entire orbit in rhabdomyosarcoma: a case report.
AB  - Rhabdomyosarcoma (RMS) is a relatively frequent tumor in children. Judicious
      combinations have markedly improved treatment results in recent years. Orbital
      localizations are treated with chemotherapy and radiotherapy. It has been
      advocated that radiotherapy be limited to the original tumor bed. This case
      report illustrates the danger of shielding part of the orbit: in a clinically
      tumor-free region before chemotherapy, which was shielded during radiotherapy, a
      local recurrence was seen while the original tumor bed remained controlled.
      Therefore, the whole content of the orbit should be irradiated in orbital RMS.

PMID- 1399575
TI  - Multifocal adult rhabdomyomas of the head and neck.
AB  - Rhabdomyomas are usually found in the myocardium. Of the extracardiac sites, the
      head and neck is the most frequent region where this rare tumor arises.
      Multifocal head and neck lesions have only been described in 11 cases. We herein
      present two additional multifocal lesions.

PMID- 1399576
TI  - Epithelial-myoepithelial carcinoma of salivary gland with metastasis to lung:
      report of a case and review of the literature.
AB  - A 63-year-old man was initially seen with multiple pulmonary nodules 14 years
      after a left parotidectomy for an epithelial-myoepithelial carcinoma of salivary
      gland. Eight and 18 months after parotidectomy, the patient had local recurrence
      of his salivary gland tumor. He remained disease-free before being seen with
      pulmonary nodules, which were evaluated by open lung biopsy. The pathologic
      features of the pulmonary nodules were identical to the salivary gland tumor
      resected 14 years earlier. This is the fourth reported case of epithelial
      myoepithelial carcinoma of salivary gland metastasizing to a distant site.

PMID- 1399577
TI  - Tumor suppressor genes.
AB  - Tumor suppressor genes are negative regulators of cell growth. When their normal
      function is compromised, absence of their inhibitory effects can lead to
      unrestrained cell cycling and growth. Strong evidence now confirms that loss of
      proper function of these genes is a common occurrence leading to cancer. Their
      failure can be caused by alterations in the gene DNA or malfunction of their
      protein products. The recent extraordinary accumulation of knowledge about these
      genes reveals that normal carcinogenesis represents breakdown of normal
      regulatory processes.

PMID- 1399578
TI  - Nasal mass in a pediatric patient.
AB  - The consultants agreed that the differential diagnosis should focus on congenital
      masses, including an encephalocele, glioma, dermoid, hamartoma, hemangioma,
      rhabdomyosarcoma, neurofibroma, and nasolacrimal duct cyst. There was some
      disagreement as to which is the best way to evaluate the mass, ranging from an
      MRI (Dr. Reilly), to CT scan (Dr. Cotton), to both MRI and CT (Dr. Koopman).
      Blood tests to evaluate pituitary function could be indicated if there was a
      sphenoid defect (Dr. Reilly). None of the experts would biopsy this lesion. All
      would proceed with a definitive resection. One surgeon would defer surgery for
      several months and then perform the resection via a biocoronal craniotomy (Dr.
      Reilly). A combined anterior craniotomy and external ethmoidectomy would be
      planned by another (Dr. Koopman). The third consultant would combine an anterior
      craniotomy with a mid-face degloving, external rhinoplasty, or lateral rhinotomy
      approach (Dr. Cotton). Routine perioperative antibiotics would only be used by
      two of the surgeons (Drs. Reilly and Koopman). If a CSF leak were encountered
      there are several options. A small lesion could be allowed to close on its own
      (Dr. Reilly). If the leak occurred while the bicoronal incision was still open or
      if the leak were large, it could be repaired from above (Drs. Reilly and
      Koopman). One surgeon would proceed with a repair from above even if the leak
      were encountered during the intranasal approach (Dr. Cotton). Only one surgeon
      would restrict postoperative activity with intubation and sedation or paralysis
      (Dr. Koopman). Regarding follow-up, no one was concerned about the final
      pathology report.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399579
TI  - Miniplate fixation of zygomatic fractures.

PMID- 1399580
TI  - Postgraduate education allowance: a regional analysis of the first year.
AB  - A comparison of accredited education sessions attended by general practitioners
      in the West of Scotland during 1990-91, the first year of the postgraduate
      education allowance, and during the previous year is presented. During 1990-91
      the mean number of half day sessions attended by each practitioner was 14.0. This
      is an increase of 36% over the number (10.3) attended during the previous year.
      The mean number of days attended during 1990-91 includes 5.5 devoted to disease
      management, 4.4 to service management, and 4.1 to health promotion. Eighty five
      per cent of practitioners attended a full day devoted to disease management, 78%
      a full day devoted to service management, and 72% to full day devoted to health
      promotion; 80% a day in two of these three categories, and 57% a day in all
      three. The average attendance exceeds the requirement of the new contract. The
      great majority of practitioners in the Region appear to be achieving the spread
      of attendance over the three categories required by the regulations.

PMID- 1399581
TI  - How do local doctors react to a hospice?
AB  - Postal questionnaires were sent to general practitioner principals and hospital
      consultants in Ayrshire a year before and again 13 months after the opening of
      the Ayrshire Hospice. Seventy-three per cent of 342 doctors replied to the first
      survey and 62% replied to the second survey. There was initially a fairly
      strongly felt need for a hospice, with median Visual Analogue Score (VAS) of 16
      ('definite need' = 0 and 'definitely no need' = 100). After the opening of the
      hospice doctors were much more enthusiastic (median VAS 5; p less than 0.0001).
      Doctors feeling no need for a hospice (VAS greater than 75) became fewer (9.6%
      before opening, 2% after). Doctors who would refer patients to a hospice, at
      first 82%, numbered 92% after opening. Seventy-one per cent of general
      practitioners and 60% of consultants had referred patients to the hospice within
      a year of opening. After opening, specialist advice with home care was considered
      the most useful aspect, in-patient beds useful, and day hospice least useful.
      Seventy-three per cent of referring doctors found the hospice a great help. In
      both surveys general practitioners and consultants felt the hospice should be run
      by a mixture of voluntary and NHS finance. Doctors appeared willing to learn
      about palliative care from hospice doctors, particularly after hospice opening.
      Doctors were initially rather dissatisfied with palliative care in existing
      hospitals, but became less so (particularly about pain control) after hospice
      opening. Surprisingly, in both surveys the attitudes of general practitioners and
      consultants were virtually identical.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399582
TI  - Audit of the quality of hospital discharge data.
AB  - An audit of the quality of computerised hospital discharge data, in General
      Medicine and Paediatrics in Dundee, showed that the national data set was often
      inaccurate. Structured discharge summaries checked by senior medical staff are
      recommended.

PMID- 1399583
TI  - Transferring at-risk babies in-utero or neonatally: a decade's experience from a
      peripheral consultant maternity unit.
AB  - All maternity cases in which babies were transferred in-utero (n = 82) or
      neonatally (n = 273) from the William Smellie Memorial Maternity Hospital to a
      regional neonatal intensive care unit during 1980-89 were studied to detect
      changing trends and outcomes. The proportion of babies transferred in-utero has
      increased and most of these transfers appear to have been justified. Forty-seven
      per cent of babies transferred neonatally were mature infants (greater than 37
      weeks) so that the need for intensive neonatal care would have been difficult to
      predict. Perinatal mortality has fallen in line with national rates, mainly due
      to the decline in mortality of premature babies transferred neonatally. The
      results do not sustain the argument for further increasing in-utero transfers.

PMID- 1399584
TI  - Medical staffing in the National Health Service in Scotland in 1990 and junior
      hospital doctor's 'promotion prospects'.

PMID- 1399585
TI  - The use of general anaesthesia and sedation in general dental practice: a survey
      in Glasgow, United Kingdom.
AB  - One hundred and sixty four of the 240 general dental practitioners on the Greater
      Glasgow Health Board family practitioner list returned a postal questionnaire on
      the current use of General Anaesthesia and sedation in their practices. Thirty
      three per cent offered GA sessions but nearly a half were in the process of
      withdrawing the service. The majority of the respondents (74.4 per cent) felt
      that a simple sedation method would attract patients. An inhalation technique was
      considered the most appropriate for general dental practice by 62 per cent of the
      dentists.

PMID- 1399586
TI  - An audit of acute asthma admissions to a respiratory unit.
AB  - A criterion based audit was performed on 90 admissions with acute asthma to a
      specialist respiratory unit using the guidelines set by the British Thoracic
      Society. Three main areas were audited including: documentation of severity
      markers in the case notes on admission, acute treatment given on admission, and
      further investigations performed. Case notes were found to be deficient in
      documentation of objective severity markers such as peak expiratory flow rate
      (52% recorded) and blood gases (72% recorded), as well as subjective markers such
      as speech (27%), air entry (58%) and exhaustion (4%). Of the total 90 admissions,
      78% were identified as having at least three out of five objective markers for
      acute severe asthma. Most of these severe cases (93%) were given corticosteroids
      but none were prescribed greater than 35% concentration of inspired oxygen. The
      majority of admissions had a chest radiograph (87%), and 56% had measurement of
      serum potassium. These results show that even in a specialised respiratory unit,
      guidelines such as those produced by the British Thoracic Society are not in
      general being adhered to. It also indicates that assessment of severity is
      inadequate, particularly for peak flow measurement, and that management is
      deficient in established treatments such as the use of high flow oxygen. As a
      result of the audit, a severity marker stamp for the case notes along with
      guidelines for treatment have been implemented in order to improve the quality of
      care delivered to patients admitted with acute asthma.

PMID- 1399587
TI  - Geriatric respite care--present practice and the potential for improvement.
AB  - A prospective Audit of patients admitted for geriatric respite care was
      undertaken. Information was obtained from patients, staff and carers for 125
      consecutive admissions over a 20 week period. The 87 clients admitted had a mean
      age of 79.6 years and 83% had a high physical/mental dependency. In contrast to
      some previous studies mortality was very low (less than 2%). One hundred and nine
      (87%) admissions were discharged home. Respite admission bed use was classified
      as shared care (971 days, n = 19), planned respite (937 days, n = 50) and crisis
      respite (809 days, n = 18). The shared care and planned group did not show
      significant differences in patient dependency or carer profile. On a population
      basis, geriatric respite care was required on a bed per 1,000 population aged 75
      and over. Patients viewed as inappropriate for geriatric care were most frequent
      in the crisis respite group, with the Geriatric Unit at times meeting shortfalls
      in other services. The sharing of key information between families/carers and
      community/hospital was, at times, deficient. The need for increased publicity
      about the service and for a carer support group was identified. Most families
      were satisfied with the care received but specific ways of improving the service
      were suggested.

PMID- 1399588
TI  - The Chief Scientist reports.... Pattern of decline in prevalence of anencephaly
      and spina bifida in a high risk area.
AB  - The results of three studies spanning the period 1964 to 1989 were aggregated in
      an attempt to identify secular trends which might contribute to aetiological
      understanding of anencephaly and spina bifida (ASB). All data related to the
      prevalence of ASB in a geographically defined population in Glasgow, a known high
      risk area of neural tube defects. Multiple sources of ascertainment were employed
      to identify affected cases, whether live births, still births or induced
      abortions following prenatal diagnosis. The birth prevalence of ASB dropped by
      82%, from 5.63 per 1,000 births in 1964-1968 to 1.04 per 1,000 births in 1979
      1989, while the pregnancy prevalence (adjusted by including induced abortions)
      declined by 46%, from 5.63 per 1,000 births in 1964-1968 to 3.02 per 1,000 births
      in 1979-1989. Thus, prenatal screening contributed just under half of the
      observed decline in ASB birth prevalence. The pregnancy prevalence appeared to
      decline throughout the 1970's and early 1980's, and to increase again,
      temporarily, in the mid-1980s. These data could be interpreted as being broadly
      consistent with socio-economic hypotheses of ASB aetiology.

PMID- 1399589
TI  - Hospital strategy and financial performance.
AB  - Five archetype strategies are studied involving productivity, diversification, or
      a hybrid approach. Manager opinions, staffing ratios, and profitability data
      bring the strategy effectiveness issue into perspective. Hospitals employing the
      productivity/defender strategy, specializing in fewer product lines, experienced
      less decline in profitability in recent years. Excess diversification appears to
      exhibit the most rapid declines in profitability.

PMID- 1399590
TI  - Application of continuous quality improvement techniques to the treatment of
      patients with hypertension.
AB  - This article reports how continuous quality improvement (CQI) techniques were
      applied to physician care of patients with hypertension. A physician task force
      at an ambulatory care center used CQI methods to address the needs of two
      important "customer" groups: (1) third party payors and (2) patients with
      hypertension. Treatment standards were defined that can also serve as a customer
      oriented product description. The task force found patients' blood pressures
      generally well controlled. Future studies will focus on appointment making,
      giving advice, and the doctor's examination as subprocesses that strongly
      influence patient satisfaction.

PMID- 1399592
TI  - Evaluating user satisfaction in a hospital environment: an exploratory study.
AB  - This article demonstrates the usefulness of user satisfaction measurement to
      pinpoint potential problem areas as well as to document application areas with
      satisfied users in hospital information systems. It discusses the rationale of
      measuring user satisfaction and the instruments to carry out the measurement
      procedure. It, then, reports the results of implementing a previously developed,
      documented, and validated user satisfaction measurement instrument in a hospital
      environment.

PMID- 1399591
TI  - Hospital board effectiveness: relationships between board training and hospital
      financial viability.
AB  - This study examined whether hospital governing boards that invest in board
      education and training are more informed and effective decision-making bodies.
      Measures of hospital financial viability (i.e., selected financial ratios and
      outcomes) are used as indicators of hospital board effectiveness. Board
      participation in educational programs was significantly associated with improved
      profitability, liquidity, and occupancy levels, suggesting that investment in the
      education of directors is likely to enhance hospital viability and thus increase
      board effectiveness.

PMID- 1399593
TI  - Strategic planning in rural health care organizations.
AB  - Is strategic planning associated with higher levels of performance in health care
      organizations? Is strategic planning effective? This article examines strategic
      planning's impact on rural hospital and rural nursing facility performance,
      organizational characteristics, and strategy. The findings suggest that strategic
      planning in rural hospitals is strongly associated with higher profits, operating
      margins and planning effectiveness, and associated to a lesser extent with lower
      costs and higher revenues per patient day. However, strategic planning does not
      appear to be associated with higher performance in nursing facilities. The
      implications for strategic planning in rural health care organizations are
      discussed.

PMID- 1399595
TI  - HCMR interview: Robert J. O'Brien. Interview by Montague Brown.

PMID- 1399594
TI  - The movement toward vertically integrated regional health systems.
AB  - Due to existing internal forces, a movement toward vertically integrated regional
      health systems is imperative in order to ensure the future viability of our
      health care system. However, in order for these systems to be successful, they
      must first overcome several imposing barriers.

PMID- 1399596
TI  - Strategies and structures for hospital risk management programs.

PMID- 1399597
TI  - [Extracutaneous malignant melanomas: clinical aspects and biology].
AB  - Approximately 5% of all malignant melanomas originate from primarily non
      cutaneous sites. They are preferentially distributed along the choroid, the
      meninges, the subserous space of the oesophagus and the intestinal tract, at
      transitional areas of mucous membranes, and along organ capsules, the
      periadventitial tissues of major blood vessels, and, occasionally, muscle
      fasciae. Little is known about their biological behaviour; the prognosis,
      however, generally has to be considered less favourable than that of primary
      cutaneous malignant melanomas, probably at least in part because they are often
      not discovered until they are in advanced stages. There are no specific clinical
      signs suggestive for non-cutaneous malignant melanomas; symptoms vary with the
      site of manifestation of the tumours. Interpretation of these clinical data based
      on results from comparative anatomical studies leads to the conclusion that
      extracutaneous malignant melanomas in humans are residuals of phylogenetically
      old, extensive and well-developed non-cutaneous pigment cell patterns
      demonstrable in a variety of lower vertebrates, which result from interactions
      between organogenesis and pigment cell development during ontogeny. This
      demonstrates that consideration of fundamental principles of developmental
      biology can give diagnostic clues to the localizations at which primary non
      cutaneous malignant melanomas may be suspected and can thus facilitate decisions
      about what diagnostic procedures are necessary.

PMID- 1399598
TI  - [Human behavior in the solar radiation field with reference to ultraviolet
      exposure].
AB  - There is a causal relation between solar ultraviolet radiation and skin cancer.
      For epidemiological investigations, quantification of the UV exposure is
      essential. To set up a risk assessment for the whole population, a representative
      survey was performed in Austria. The questionnaire refers to three sectors of
      everyday life: work, recreation and holidays; in addition the use of solaria is
      asked about for a further investigation. The UV exposure caused by humans'
      behaviour in the field of solar radiation was analysed from various demographic
      aspects. For some subpopulations the UV exposure sustained during work,
      recreation and holidays was compared. Groups with high occupational UV exposure
      show a weaker tendency to stay outdoors during leisure time and holidays than
      groups characterized by high UV exposure in their leisure time, who also prefer
      sun-intensive activities during holidays.

PMID- 1399599
TI  - [Immunogenetic studies of familial occurrence of progressive systemic scleroderma
      and circumscribed scleroderma].
AB  - Two different forms of scleroderma in one family are described: the mother
      suffers from systemic sclerosis and her daughter from linear morphoea. The
      observed HLA antigens indicate that systemic sclerosis and morphoea have various
      features in common. The immunogenetic data can be used to calculate the
      aetiological and preventive fractions, which together with environmental hazards
      and other risk factors describe the HLA-associated potential for provocation of
      scleroderma.

PMID- 1399600
TI  - [Osteomalacia as an apparently rare side effect of oral fumaric acid therapy.
      Secondary DeToni-Debre Fanconi syndrome in the adult].
AB  - A case of fully reversible tubular toxicity with consecutive metabolic osteopathy
      following systemic fumaric acid therapy is reported. This secondary effect of
      oral fumaric acid therapy obviously occurs very rarely, never having been
      described before. A 46-year-old female patient with a long history of recurrent
      palmoplantar psoriasis underwent oral treatment with fumaric acid and its esters
      in accordance with the Schafer method, preceding attempts at curative treatment
      with conventional antipsoriatic agents having proved unsatisfactory. Two months
      later, the patient started to experience arthralgia, back pain in the early hours
      of the morning and myalgia with increasing frequency, progressing to disablement
      in moving and walking and, finally, to total immobility. Not until 9 months later
      was the reason for these severe disabilities found: they stemmed from
      hypophosphataemic osteomalacia as a result of a complex disturbance of the renal
      tubular system. The clinical symptoms and the results of laboratory chemistry
      tests returned to normal as soon as fumaric acid medication was discontinued. Two
      attempts at reexposure confirmed the causal relationship. Oral fumaric acid
      medication should never be administered without clinical and chemical controls.

PMID- 1399601
TI  - [Quantitative analysis of recurrence and spontaneous regression of basalioma
      parts left in situ].
AB  - To some extent, parts of basalomas found remaining in situ following tumour
      excision tend to spontaneous regression. This is a well-known phenomenon and has
      significance for the recurrence of incompletely excised tumors. The present study
      involved a quantitative investigation of the relationship between recurrence and
      spontaneous regression. Following precisely defined excision of basalomas, the
      entire exterior of the excised material was examined by contrast microscopy in HE
      stained paraffin sections (3-dimensional histology). Whenever tumour outgrowths
      were found, it was possible to document exactly their type, localization, extent,
      and depth of invasion. In 66 such cases no follow-up operation was performed, but
      only a follow-up examination after a minimum of 31 and a maximum of 113 months
      (average: 60 months). Only 50% of these undisturbed tumour outgrowths resulted in
      a recurrence during the follow-up period. A very high rate of spontaneous
      regression (71%) was found among the solid tumour outgrowths, but a significantly
      lower rate (19%) among the fibrosing tumours. Moreover, regression was dependent
      on the tumour remnant's mass and the clinical diameter of the tumour removed. It
      was independent of the depth of infiltration. Although the rate of spontaneous
      regression of tumour outgrowths persisting after therapy is relatively high, it
      cannot be predicted in individual cases. It is not possible to be certain that
      tumour removal has been achieved unless micrographic surgery has been continued
      until complete absence of tumour is proved. In all procedures that are not
      subsequently monitored, an unacceptably high rate of recurrence must be expected,
      especially in the case of fibrosing basaloma. This is commented on at length.

PMID- 1399602
TI  - [HMB 45 positive balloon cells in combined nevi].
AB  - The combined naevus is made up of two components, one resembling a melanocytic
      naevus, the other a blue naevus. Clinically, these naevi do not give any obvious
      cause for concern. Histological examination shows that the combined naevus
      consists of a superficial melanocytic naevus and a deep-seated spindle cell blue
      naevus. There is a rare variant in which the pigmented spindle cells of the
      "blue" naevus are replaced by large balloon cells varying in melanin content.
      These combined naevi, because of the large cells with abundant cytoplasm, closely
      resemble malignant melanoma. As a further aid to diagnosis we used the monoclonal
      antibody HMB 45. In our study, the vesicular cells in all seven combined naevi
      examined reacted strongly with HMB 45. It is suggested that HMB 45 is not always
      helpful in differentiating between melanoma and naevi.

PMID- 1399603
TI  - [A lupus-vulgaris like atypical mycobacteriosis caused by Mycobacterium xenopi
      (lupus xenopi)].
AB  - A case of lupus-vulgaris-like infection caused by Mycobacterium xenopi in a 62
      year-old immunocompetent female patient is presented. A large cutaneous
      infiltration was seen in the right periorbital region. Histological examination
      revealed a granulomatous reaction of epithelioid cells and giant cells. M. xenopi
      was isolated from biopsy material and tuberculosis could be excluded. Isoniazid
      was effective in healing the lesion within a year. Such infections are well known
      for other mycobacteria but to our knowledge had not yet been described for M.
      xenopi. The characteristics of human infections with M. xenopi are summarized in
      a review of the literature and criteria for the diagnosis of atypical cutaneous
      mycobacterioses are proposed.

PMID- 1399604
TI  - [Erosive pustular dermatosis of the scalp after zoster ophthalmicus and trauma].
AB  - Erosive pustular dermatosis of the scalp (EPDS), first described in 1979, is a
      rare, chronic, pustular condition with scarring alopecia, and nonspecific
      histological findings. While the initial responded to steroids is good, it can be
      treated successfully by oral administration of zinc sulphate. Local trauma has
      recently been suggested to play a role in the pathogenesis of EPDS. The
      differential diagnosis of EPDS includes folliculitis decalvans, sterile
      eosinophilic pustulosis Ofuji, pustular psoriasis vulgaris, trichophytosis,
      Perifolliculitis capitis abscedens et suffodiens, pemphigus vulgaris and
      cicatricial pemphigoid. We present the cases of a 74-year-old woman suffering
      from EPDS following herpes zoster ophthalmicus and of a 54-year-old man in whom
      EPDS followed a head injury.

PMID- 1399605
TI  - [Erythema nodosum and non-Hodgkin lymphoma].
AB  - A 36-year-old woman presenting with erythematous painful tender inflammatory
      nodular lesions on both knees, shins and ankles is reported. Erythema nodosum
      (EN) was diagnosed. Further clinical examination revealed hilar lymphadenopathy.
      A lymph node was removed for histological examination, and a centroblastic non
      Hodgkin lymphoma was diagnosed. Remarkably, in this patient EN occurred before
      the haematological malignancy was detected.

PMID- 1399606
TI  - [Eccrine hamartoma of the sweat glands simulating localized unilateral
      hyperhidrosis].
AB  - We report on the case of a 31-year-old woman who presented with localized
      unilateral hyperhidrosis on her lower right arm. Histological features showed a
      hamartoma of the eccrine sweat glands. Because she was afraid of being
      overweight, the patient took an appetite depressant. Under this self-medication
      complete cessation of the localized hyperhidrosis was observed.

PMID- 1399607
TI  - [Rhabdomyosarcoma: differential diagnosis of cutaneous tumors in childhood].
AB  - Primary rhabdomyosarcoma can arise in the skin, but there are few reports on this
      common childhood malignancy in the dermatological literature. We report on a male
      infant with a cutaneous tumour growing on the right nasal bridge since his 10th
      week of life. Clinically the tumour mimicked pilomatrixoma. Histological and
      immunohistological examination of the skin tumour and of subsequent lymph node
      metastases revealed rhabdomyosarcoma of the alveolar growth pattern. Our patient
      died at the age of 4 years of disseminated organ metastases.

PMID- 1399608
TI  - [Epicutaneous testing of unfamiliar occupational allergens].

PMID- 1399609
TI  - [Drug reaction to amoxicillin simulating toxic pustular dermatosis].

PMID- 1399611
TI  - [Topical steroids with improved uses/lessened risks. Symposium. New York, 10 June
      1992].

PMID- 1399610
TI  - [Hydrocolloid dressings].

PMID- 1399612
TI  - Ethical issues in radiation protection--the 1992 Sievert Lecture.

PMID- 1399613
TI  - Estimates of absorption of radiofrequency radiation by the embryo and fetus
      during pregnancy.
AB  - This paper reports that the specific absorption rate induced in the embryo or
      fetus can exceed that recommended for the general public when the mother is
      exposed to radiofrequency radiation at the occupational limits. This result
      applies to two-tiered radiofrequency radiation standards where a factor of 5
      differentiates occupational and nonoccupational exposure limits. Using simple
      axisymmetric geometries for the pregnant worker, and assuming plane wave
      exposures, a finite element method provides estimates of prenatal exposure.
      Various layered shapes are used to model skin, fat, uterus, blood, embryonic, and
      fetal tissues. Applying current exposure limits given by IRPA, ANSI, and SAA, the
      results indicate that overexposures to the embryo or fetus can occur from early
      pregnancy at 80-100 MHz, and in late pregnancy across the range 300-1500 MHz.

PMID- 1399614
TI  - Beta-ray dose distributions from point sources in an infinite water medium.
AB  - The ACCEPT Monte Carlo code has been used to calculate radial dose distributions
      around isotropic point sources of monoenergetic electrons between 0.01 and 10 MeV
      in an infinite water medium. The results were averaged over beta spectra to
      derive distributions for 147 beta emitters of which 32 are presented. More
      extensive tables of distributions will be presented in a report. Distributions
      for monoenergetic electrons agree with recent ETRAN-code calculations of Berger
      and Seltzer within 2%, except at very short distances where there are differences
      up to several percent. Results calculated by the EGS4 code differ by up to a few
      percent. Distributions for beta emitters are in excellent agreement with both
      experimental results and ETRAN and EGS4 calculations, except at very short
      distances.

PMID- 1399615
TI  - Study of 222Rn permeation through polymer membranes: application to continuous
      measurement of 222Rn in water.
AB  - Membranes that exclude water but are permeable to radon can extend the range of
      environments where many radon detection systems could operate. We have studied
      the permeation of 222Rn through polypropylene membranes separating air and water
      phases. The permeation coefficient and the activation energy were calculated for
      various conditions. Potential applications, such as in situ detection of radon in
      water, are discussed.

PMID- 1399616
TI  - Residential radon exposure and lung cancer in Swedish women.
AB  - A case-control study was undertaken to investigate the role of residential radon
      exposure for lung cancer. The study included 210 women with lung cancer diagnosed
      from 1983-1986 in the county of Stockholm and 191 hospital and 209 population
      controls. Interviews provided information on lifetime residences and smoking.
      Radon concentrations measured in 1,573 residences of the study subjects showed a
      lognormal distribution with arithmetic and geometric means of 127.7 and 96.0 Bq m
      3, respectively. Lung cancer risks tended to increase with estimated radon
      exposure, reaching a relative risk of 1.7 (95% confidence interval: 1.0-2.9) in
      women having an average radon level exceeding 150 Bq m-3 (4 pCi L-1). Stronger
      associations were suggested in younger persons and risk estimates appeared to be
      within the same range as those projected for miners. However, further studies are
      needed to clarify the level of risk associated with exposure to residential
      radon.

PMID- 1399617
TI  - Daily intakes of 232Th and 238U in Japanese males.
AB  - Diet samples were collected by a duplicate portion method from 31 locations in
      Japan and were analyzed by inductively coupled plasma mass spectrometry. Average
      daily intakes per adult male were estimated at 1.7 mBq for 232Th and 8.8 mBq for
      238U.

PMID- 1399619
TI  - Exact calculation of probabilities of false positives and false negatives for low
      background counting.
AB  - The purpose of this paper is to demonstrate the derivation and use of exact
      formulas, and their algorithms, for calculating the probabilities alpha of Type I
      errors, and beta of Type II errors, for low blank total counts (Poisson
      distributed). The calculations are carried out to examine the alpha and beta
      probabilities at low blank levels of the decision level (DL) and minimum
      detectable amount (MDA) formulations as adopted in the Health Physics Society
      Standard, "Performance Criteria for Radiobioassay." These formulations are
      consistent with those published by L.A. Currie, which have received wide
      acceptance in defining lower limits of detection (LLD). Although Currie's
      formulation was derived assuming a normal distribution in net counts, the
      behavior of the distribution of net counts at low count levels, which is a
      distribution of the difference between two Poisson variates, is such that the MDA
      formulation in the standard could be considered acceptable for the purpose of
      providing one simple formulation of MDA. The derivations in this note can also be
      useful in other problems involving differences in Poisson variates, such as those
      in certain population studies.

PMID- 1399618
TI  - Decorporation of plutonium by oral administration of a partially lipophilic
      polyaminocarboxylic acid.
AB  - A new, orally administered, partially lipophilic polyaminocarboxylic acid
      chelator was tested for its ability to remove incorporated 239Pu deposits in
      rats. Animals were injected with 239Pu-citrate and 14 d later were treated for an
      additional 10 d with docosyl-triethylenetetraminepentaacetic acid (C22TT) added
      to the diet. There were significant reductions in the 239Pu content of selected
      organs in the chelated animals compared with controls. These results suggest that
      this class of chelators should be studied further for their ability to remove
      plutonium deposits from the body when given orally.

PMID- 1399620
TI  - Gamma distribution and house 222Rn measurements.
AB  - The statistical distribution of 222Rn measurements from basements and first
      floors of homes in northeastern Pennsylvania was investigated. The gamma
      distribution was statistically significantly superior to the normal distribution
      (p less than 0.005) in describing the frequency distribution of the logarithm of
      observed 222Rn levels. The fit to the data was closer both in the central portion
      and in the upper tail. The gamma distribution has certain characteristics that
      make it generally useful in the study of environmental toxic agents where several
      different exposures over a lifetime occur and must be combined, as for risk
      assessment or for statistical power calculations for epidemiologic studies.

PMID- 1399621
TI  - Effect of sorption barriers on the radon fluence rate from soil.
AB  - The fluence rate of radon from soil as affected by active sorption barriers
      [activated carbon (AC) and mordenite], soil moisture content, and temperature was
      measured over a period of 964 d. (To limit the level of radon in indoor
      environments, an active sorption barrier potentially could be mixed with soil
      placed adjacent to the substructures of buildings.) AC, mixed with the top layer
      of soil in columns, markedly reduced the fluence rate of radon from soil over the
      entire time of the experiment and at all moisture contents and temperatures
      examined. Mordenite, on the other hand, was not effective in decreasing the
      fluence rate. AC also has a relatively high sorption capacity for aqueous lead
      species. (Stable lead isotopes are end-products in the uranium and thorium decay
      series of which radon isotopes are members.) Thus, the long-term (decades)
      efficacy of AC in sorbing radon in a soil environment will not be compromised by
      the blocking of its sorption sites by lead.

PMID- 1399622
TI  - Compliance with EPA guidelines for follow-up testing and mitigation after radon
      screening measurements.
AB  - A survey was taken of 314 individuals, 55 of whom had residences that exceeded
      the EPA action level of 148 Bq m-3 (4 pCi L-1) of radon as measured by a medical
      center radon testing service. The survey was designed to assess whether these
      individuals followed the 1986 EPA guidelines for follow-up testing and
      mitigation. The survey indicated 41% of respondents performed follow-up tests and
      16% of the respondents performed some form of mitigation. Some respondents had
      performed mitigation after inadequate or no follow-up radon tests. There was a
      positive relationship between follow-up testing and mitigation and higher initial
      radon screening values.

PMID- 1399623
TI  - Photon shielding for 241Am surface and point sources.
AB  - To determine radiation protection requirements for work with actinide elements, a
      method for rapidly estimating effective dose-equivalent rates from low-energy
      photons has been developed. This paper describes results obtained from a personal
      computer program that incorporates the point kernel technique to predict
      radiation fields from shielded and unshielded sources containing 241Am.
      Information generated has been used to determine procedures and to design
      facilities for handling actinides at Argonne National Laboratory's site at the
      Idaho National Engineering Laboratory. Area or point sources can be treated;
      effects of Compton scattering in air and in solid shields are considered. Users
      can select an appropriate response function; their choice has a strong influence
      on predicted dose rates from unshielded sources.

PMID- 1399624
TI  - A model for radon gas adsorption on charcoal for open-faced canisters in an
      active environment.
AB  - It was previously suggested that the calibration factor (CF) relating the
      detected activity (A) of the radon decay products 214Bi and 214Pb within a
      charcoal canister to the radon concentration (CR) in air be defined as CF = A/(E
      x DF x CR), where E is the counting efficiency of the detector for 214Bi and
      214Pb gamma rays, and DF is a factor accounting for decay during the time (tD)
      from the end of the exposure until the canister is counted; i.e., DF = exp(
      lambda RPtD), where lambda RP is the physical decay constant for radon. With CF
      defined as above, a kinetic model for the adsorption of radon gas on charcoal in
      humid air predicts that CF (in m3) can be written for CR in Bq m-3, A in cpm, and
      E in cpm Bq-1 as CF = alpha[1-exp(-delta t)] + beta[1 - exp(-delta t)]M(t), where
      alpha, beta, and delta are free parameters, t is the canister exposure time in
      hours, and M(t) is the canister water mass gain in grams in time t. For CF data
      for the U.S. Environmental Protection Agency's open-faced canisters in an active
      (with respect to air flow) environmental chamber, delta = (0.046 +/- 0.002)h-1,
      and exp(-delta t) much less than 1 for t greater than or equal to 3 d. Also,
      alpha = (0.342 +/- 0.002)m3, and beta = -(0.0123 +/- 0.0001)m3g-1.

PMID- 1399625
TI  - Radioactivity range for the dose calibrator linearity test.

PMID- 1399626
TI  - Excretion of 201Tl in human breast milk.

PMID- 1399627
TI  - Comment on determining the lower limit of detection for personnel dosimetry
      systems.

PMID- 1399628
TI  - Statistical significance of supra-linearity of dose-response in the A-bomb study.

PMID- 1399629
TI  - Supra-linear dose-response for radiation-induced cancer: no basis for Piepho's
      doubt.

PMID- 1399630
TI  - 1992 Distinguished Scientific Achievement Award presented to Bernard L. Cohen.

PMID- 1399631
TI  - 1992 Distinguished Scientific Achievement Award presented to James E. Turner.

PMID- 1399632
TI  - 1992 Distinguished Scientific Achievement Award Memorialization presented in
      memory of Marvin M. D. Williams.

PMID- 1399633
TI  - 1992 Elda E. Anderson Award presented to Kimberlee J. Kearfott.

PMID- 1399634
TI  - 1992 William McAdams Outstanding Service Award. Lester A. Slaback, Jr.

PMID- 1399635
TI  - 1992 National Registry of Radiation Protection Technologists Arthur F. Humm, Jr.,
      Memorial Award presented to H. Wade Patterson.

PMID- 1399636
TI  - Residential radon exposure and lung cancer: an overview of ongoing studies.
AB  - This review paper summarizes the ongoing case/control studies of residential
      radon exposure and lung cancer. Discussion is offered in the areas of lung cancer
      risk factors, sample size requirements, radon exposure assessment, and meta
      analysis. This is an important topic that deserves a "best effort" study design.

PMID- 1399637
TI  - Radiation exposure inside reinforced concrete buildings at Nagasaki.
AB  - In this study, the radiation doses to occupants of two reinforced concrete
      buildings at Nagasaki, who survived the immediate effects of the nuclear weapon
      detonation, are determined using state-of-the-art radiation transport techniques.
      The radiation doses at all locations in the buildings are calculated using the
      Three-Dimensional Oak Ridge Discrete Ordinates Radiation Transport Code which was
      constructed especially for this task. This code represents a new and unique
      capability that has been previously reported. This study resulted in case-by-case
      lists of doses to occupants and an uncertainty analysis. These data have been
      used in a companion study as the basis for determining a new value of the dose
      producing a 50% risk of fatality.

PMID- 1399638
TI  - Estimation of median human lethal radiation dose computed from data on occupants
      of reinforced concrete structures in Nagasaki, Japan.
AB  - This paper presents an estimate of the median lethal dose for humans exposed to
      total-body irradiation and not subsequently treated for radiation sickness. The
      median lethal dose was estimated from calculated doses to young adults who were
      inside two reinforced concrete buildings that remained standing in Nagasaki after
      the atomic detonation. The individuals in this study, none of whom have
      previously had calculated doses, were identified from a detailed survey done
      previously. Radiation dose to the bone marrow, which was taken as the critical
      radiation site, was calculated for each individual by the Engineering Physics and
      Mathematics Division of the Oak Ridge National Laboratory using a new three
      dimensional discrete-ordinates radiation transport code that was developed and
      validated for this study using the latest site geometry, radiation yield, and
      spectra data. The study cohort consisted of 75 individuals who either survived >
      60 d or died between the second and 60th d postirradiation due to radiation
      injury, without burns or other serious injury. Median lethal dose estimates were
      calculated using both logarithmic (2.9 Gy) and linear (3.4 Gy) dose scales. Both
      calculations, which met statistical validity tests, support previous estimates of
      the median lethal dose based solely on human data, which cluster around 3 Gy.

PMID- 1399639
TI  - Benchmark test of transport calculations of gold and nickel activation with
      implications for neutron kerma at Hiroshima.
AB  - A benchmark test of the Monte Carlo neutron and photon transport code system
      (MCNP) was performed using a 252Cf fission neutron source to validate the use of
      the code for the energy spectrum analyses of Hiroshima atomic bomb neutrons.
      Nuclear data libraries used in the Monte Carlo neutron and photon transport code
      calculation were ENDF/B-III, ENDF/B-IV, LASL-SUB, and ENDL-73. The neutron
      moderators used were granite (the main component of which is SiO2, with a small
      fraction of hydrogen), Newlight [polyethylene with 3.7% boron (natural)],
      ammonium chloride (NH4Cl), and water (H2O). Each moderator was 65 cm thick. The
      neutron detectors were gold and nickel foils, which were used to detect thermal
      and epithermal neutrons (4.9 eV) and fast neutrons (> 0.5 MeV), respectively.
      Measured activity data from neutron-irradiated gold and nickel foils in these
      moderators decreased to about 1/1,000th or 1/10,000th, which correspond to about
      1,500 m ground distance from the hypocenter in Hiroshima. For both gold and
      nickel detectors, the measured activities and the calculated values agreed within
      10%. The slopes of the depth-yield relations in each moderator, except granite,
      were similar for neutrons detected by the gold and nickel foils. From the results
      of these studies, the Monte Carlo neutron and photon transport code was verified
      to be accurate enough for use with the elements hydrogen, carbon, nitrogen,
      oxygen, silicon, chlorine, and cadmium, and for the incident 252Cf fission
      spectrum neutrons.

PMID- 1399640
TI  - Navajo birth outcomes in the Shiprock uranium mining area.
AB  - The role of environmental radiation in the etiology of birth defects,
      stillbirths, and other adverse outcomes of pregnancy was evaluated for 13,329
      Navajos born at the Public Health Service/Indian Health Service Hospital in the
      Shiprock, NM, uranium mining area (1964-1981). More than 320 kinds of defective
      congenital conditions were abstracted from hospital records. Using a nested case
      control design, families of 266 pairs of index and control births were
      interviewed. The only statistically significant association between uranium
      operations and unfavorable birth outcome was identified with the mother living
      near tailings or mine dumps. Among the fathers who worked in the mines, those of
      the index cases had histories of more years of work exposure but not necessarily
      greater gonadal dosage of radiation. Also, birth defects increased significantly
      when either parent worked in the Shiprock electronics assembly plant. Overall,
      the associations between adverse pregnancy outcome and exposure to radiation were
      weak and must be interpreted with caution with respect to implying a biogenetic
      basis.

PMID- 1399641
TI  - Estimates of embryonic and fetal doses from 239Pu.
AB  - Previously reported studies on the transfer of 238Pu from the maternal
      circulation to the developing embryo and fetus in rats and guinea pigs have
      provided data for developing dosimetric models. The highest concentrations of
      238Pu were measured in the yolk sac. In late gestation, preferential uptake of
      238Pu in liver and bone was observed. The data obtained, together with other
      published information, have been used to estimate in utero doses to hemopoietic
      tissues, taking account of transfer to the blastocyst/egg cylinder, yolk sac,
      liver, and bone marrow. From animal data, the concentration ratios relative to
      maternal liver for these tissues were taken to be 0.1, 2, 0.01, and 0.02,
      respectively, and were applied to periods of human gestation of 0-2.5 wk, 2.5-6
      wk, 6-12 wk, and 12-38 wk, respectively. Doses to fetal tissues from 239Pu were
      calculated for chronic ingestion by the mother for a total of 1.8 kBq 239Pu
      during the year of pregnancy, giving a committed effective dose to the mother of
      1 mSv. On this basis, the total in utero dose to hemopoietic tissue was about 2
      microSv compared with red bone marrow doses of 34 microSv to the mother for the
      year. The yolk sac and bone marrow dominated in utero doses. The total dose to
      hemopoietic tissue in the offspring to age 70 y, taking into account the activity
      present at birth and including in utero doses, was estimated as 24 microSv
      compared with a maternal dose to red bone marrow of 2.5 mSv. An acute maternal
      intake of 1.8 kBq by ingestion during the period of yolk sac hemopoiesis would
      result in the highest in utero dose, estimated at about 36 microSv. However,
      activity at birth would be lower, giving only a small additional dose.

PMID- 1399642
TI  - The measurement of activity-weighted size distributions of radon progeny: methods
      and laboratory intercomparison studies.
AB  - Over the past 5 y, there have been significant improvements in measurement of
      activity-weighted size distributions of airborne radon decay products. The
      modification of screen diffusion batteries to incorporate multiple screens of
      differing mesh number, called graded screen arrays, have permitted improved size
      resolution below 10 nm such that the size distributions can now be determined
      down to molecular sized activities (0.5 nm). In order to ascertain the utility
      and reliability of such systems, several intercomparison tests have been
      performed in a 2.4 m3 radon chamber in which particles of varying size have been
      produced by introducing SO2 and H2O along with the radon to the chamber. In April
      1988, intercomparison studies were performed between direct measurements of the
      activity-weighted size distributions as measured by graded screen arrays and an
      indirect measurement of the distribution obtained by measuring the number size
      distribution with a differential mobility analyzer and multiplying by the
      theoretical attachment rate. Good agreement was obtained in these measurements. A
      second set of intercomparison studies among a number of groups with graded screen
      array systems was made in April 1989 with the objective of resolving spectral
      structure below 10 nm. Again, generally good agreement among the various groups
      was obtained although some differences were noted. It is thus concluded that such
      systems can be constructed and can be useful in making routine measurements of
      activity-weighted size distributions with reasonable confidence in the results
      obtained.

PMID- 1399643
TI  - A nuclear incident at a power plant in Sosnovyy Bor, Russia.
AB  - Several radionuclides were identified in the surface air in Finland following a
      nuclear incident in Sosnovyy Bor on 24 March 1992. In addition to gases, the
      release contained small uranium fuel particles. The radionuclide concentrations
      were of the same order of magnitude as the concentrations detected in Northern
      Finland in 1987 after the nuclear explosion in Novaya Zemlya (1 mBq m-3) but five
      orders of magnitude smaller than the concentrations during the Chernobyl accident
      in 1986. The radiological consequences in Finland were insignificant. However,
      studies show that even a minor release, across the sea and more than 100 km away,
      can be detected and important information, including the time of the incident and
      the composition of the release and the burn-up of the damaged fuel, can be
      revealed by the most accurate radioactivity measurements.

PMID- 1399644
TI  - 137Cs uptake with cafeteria food after the Chernobyl accident.
AB  - After the Chernobyl accident, the activity concentrations of radiocesium were
      measured in both the meals served at the cafeteria of a research center and in
      the employees eating there. The time-dependent means of monthly 137Cs activities
      in meals and people show a similar distribution pattern with highest values
      between March and July 1987, i.e., only 1 y after the accident. In meals, the
      highest activities were found when the menu consisted of pork, milk, or milk
      products. The 50-y cumulative effective dose calculated from the whole-body
      measurements is 0.21 mSv for male and 0.15 mSv for female employees. Cafeteria
      food contributed only a small share to this exposure.

PMID- 1399645
TI  - Risk of leukemia caused by diagnostic x-rays.
AB  - Using BEIR V risk estimates and age-specific population dose estimates, we
      estimate that approximately 12% of leukemias may be attributable to diagnostic x
      rays. Earlier estimates were markedly lower (< or = 1%) because of their use of
      earlier risk coefficients, different dose rate effectiveness factors, and, in one
      case, a methodological error.

PMID- 1399646
TI  - Radiation protection design for a clinical positron emission tomography imaging
      suite.
AB  - Radiation exposures due to patient sources, a pneumatic transport system, and gas
      lines in a positron emission tomography imaging facility are estimated for heavy
      clinical work loads. For simple source approximations and estimated study
      activities and times, exposure rates are computed that are larger than those
      anticipated in traditional nuclear medical imaging facilities. Measurements of
      exposure rates indicate that such an approach will result in conservative
      estimates of exposure by a factor of 1.2-6.3. Exposure rates due to gas lines may
      be kept at reasonable levels by careful planning of the routing of the line and
      by using high flow rates and small bore tubing. If reasonable care is taken to
      maintain the system so that only a limited number of failures occur, the doses
      due to pneumatic transport system operation are also small. The nonextremity
      doses to personnel and other individuals not involved in radiotracer preparation
      are estimated to be highest due to exposure to the patient sources. Shielding for
      511 keV photons may help to minimize exposure. Several practical suggestions are
      given for further reducing exposure to personnel.

PMID- 1399647
TI  - Response to Drs Puskin and Nelson note.

PMID- 1399648
TI  - Is a cGy a cGy or 10 mGy?

PMID- 1399649
TI  - ELF magnetic field measurements: units of bedlam.

PMID- 1399650
TI  - ICRP recommendations of the derived thorium excretion levels for occupational
      workers--a viewpoint.

PMID- 1399652
TI  - Home care for the disabled elderly: predictors and expected costs.
AB  - While interest in publicly funded home care for the disabled elderly is keen,
      basic policy issues need to be addressed before an appropriate program can be
      adopted and financed. This article presents findings from a study in which the
      cost implications of anticipated behavioral responses (for example, caregiver
      substitution) are estimated. Using simulation techniques, the results demonstrate
      that anticipated behavioral responses would likely add between $1.8 and $2.7
      billion (1990 dollars) to the costs of a public home care program. Results from a
      variety of cost simulations are presented. The data base for the study was the
      1982 National Long-Term Care Survey.

PMID- 1399651
TI  - The use of formal and informal home care by the disabled elderly.
AB  - Using data from the Channeling experiment, this article analyzes the factors
      associated with the amount of formal and informal home care received by the
      disabled elderly. The amounts of formal and informal home care used increase with
      disability, as well as with other measures of need for care. The use of formal
      care increases, and the use of informal care decreases, with income. The
      availability of immediate family increases reliance on informal care and reduces
      reliance on formal care. The findings have implications for the design of
      proposed programs to expand publicly financed home care for the disabled elderly.

PMID- 1399653
TI  - Program factors that influence utilization of adult day care.
AB  - Health planners, policymakers, and providers urgently require methods and
      information that explain the factors that affect health services utilization.
      This information is especially critical for planning programs that are effective
      in maintaining the burgeoning elderly population in community care. In this
      study, correlation and regression analyses examined the characteristics of adult
      day care (ADC) centers that were associated with utilization as operationalized
      by demand for and actual attendance in 822 centers. Community, client population,
      services and activities, and structural characteristics were associated with
      demand per center whereas the social environment of the ADC center was not. The
      attendance rate was most strongly affected by services and activities and
      structural characteristics. The significance of the study, its limitations, and
      future directions for research are discussed.

PMID- 1399654
TI  - Mammography referrals for elderly women: is Medicare reimbursement likely to make
      a difference?
AB  - Data from a survey of primary care physicians practicing in Long Island, New York
      in 1990 show that physicians report that they are less likely to refer all of
      their elderly female patients--those 75 years of age and older--for routine
      screening mammograms than their patients age 50 to 75. According to physicians'
      self-reports, out-of-pocket costs to the patient for screening mammography are
      not considered a major deterrent to referrals in this age group. Physicians'
      decisions to refer elderly patients are affected by the patients' state of health
      and are associated with the specialty of the physician:
      obstetrician/gynecologists (OBGYNs) are more likely to make routine referrals of
      elderly patients for screening mammography than are family practitioners and
      general internists. The results of this analysis suggest that the new Medicare
      reimbursement for biennial screening mammograms will not result in immediate
      increases in utilization by elderly women, unless their physicians become more
      convinced of the utility of widespread mammographic screening for the elderly
      patient.

PMID- 1399655
TI  - A longitudinal analysis of the relationship between in-hospital mortality in New
      York State and the volume of abdominal aortic aneurysm surgeries performed.
AB  - This study uses New York State hospital discharge data to examine the
      relationship between in-hospital mortality for a patient receiving an abdominal
      aortic aneurysm resection and the volume of aneurysm operations performed in the
      previous year at the hospital where the operation took place and by the surgeon
      performing the operation. Previous research on this topic is extended in several
      respects: (1) A three-year data base is used to examine the manner in which
      hospital and surgeon volume jointly affect mortality rate and to examine ruptured
      and unruptured aneurysms separately; (2) a six-year data base is used to study
      the "practice makes perfect" hypothesis and the "selective referral" hypothesis;
      and (3) the degree of specialization of high-volume surgeons is contrasted with
      that of other surgeons. The results demonstrate a significant inverse
      relationship between hospital volume and mortality rate for unruptured aneurysms.
      Further, very few surgeons substantially increased their aneurysm surgery volumes
      in the six-year study period. Weak selective referral effects were found for both
      surgeons and hospitals, and higher-volume aneurysm surgeons tended to have much
      higher specialization rates.

PMID- 1399656
TI  - Governing board structure, business strategy, and performance of acute care
      hospitals: a contingency perspective.
AB  - Contingency theory suggests that for a hospital governing board to be effective
      in taking on a more active role in strategic management, the board needs to be
      structured to complement the overall strategy of the organization. A survey study
      was conducted to examine the strategies of acute care hospitals as related to the
      structural characteristics of their governing boards. After controlling for
      organizational size and system membership, results indicated a significant
      relationship between the governing board structure of 109 acute care hospitals
      and their overall business strategy. Strategy also accounted for more of the
      variance in board structure than either organization size or system membership.
      Finally, the greater the match between board structure and hospital strategy, the
      stronger the hospitals' financial performance.

PMID- 1399657
TI  - Age distribution and turnover of physicians in nonmetropolitan counties of the
      United States.
AB  - Using data for 1975 to 1985 from the Area Resource File (ARF), net number changes
      in different age groups of physicians practicing in nonmetropolitan counties are
      examined. Small net increases are seen in the higher age groups in most county
      size categories but the most striking change is large increases in the age groups
      up to age 44. Family practitioners show a net decline in all county size
      categories for ages 45-54, but these are offset by increases in medical
      specialists. In counties of less than 25,000 population, the rate of turnover of
      physicians over the 1983-1988 period was 25 percent; physicians exiting these
      counties had a mean age of 52.3 years. The data indicate that aging of physicians
      in rural counties should not affect maintenance of current supply in the short
      run, but that increasing the physician-to-population ratio in areas with less
      adequate supply will be difficult, particularly if the rate of increase of
      younger physicians in nonmetropolitan counties does not continue.

PMID- 1399658
TI  - The "other" intensive care unit.

PMID- 1399660
TI  - Taking the mystery out of rhythm interpretation: atrial electrograms.
AB  - OBJECTIVE: To verify cardiac rhythms in which diagnosis from conventional surface
      recordings was unclear. DESIGN: Approximately five electrograms were recorded
      each week from randomly selected patients who had undergone cardiac surgery in a
      two-year period from 1989 to 1991. SETTING: A 1000 bed acute care medical
      facility that provides care to more than 1300 patients per year after open heart
      surgery. PATIENTS: Adult patients in the surgical intensive care unit or stepdown
      units who were recovering from coronary artery bypass grafting, valve replacement
      or repair, aneurysm resection, and/or atrial and ventricular septal defect
      repairs. RESULTS: The atrial electrogram was used to diagnose various
      dysrhythmias. The most frequent application was the verification of atrial
      flutter, atrial fibrillation, and junctional rhythm. Another use was to
      differentiate between ventricular tachycardia and supraventricular tachycardia
      with aberrant conduction. CONCLUSION: Critical care clinicians caring for
      patients who have undergone cardiac surgery must be proficient at rapid, accurate
      rhythm interpretation to give appropriate treatment. The use of atrial
      electrograms can be extremely helpful in rhythm interpretation and clarification
      for this population of patients.

PMID- 1399659
TI  - William Harvey, MD, FRCP (1578-1657) and the historic development of the
      circulation of the blood.

PMID- 1399661
TI  - Accuracy of heart rate assessment in atrial fibrillation.
AB  - OBJECTIVE: To determine the most accurate technique to measure the heart rate
      during atrial fibrillation by use of three counting intervals, 15, 30, and 60
      seconds, and two methods, apical and radial pulse measurement. DESIGN: A quasi
      experimental, repeated measures factorial design was used to determine absolute
      error (amount of error ignoring direction of error) between heart rates obtained
      from six randomly ordered pulse measurements taken of one man in chronic atrial
      fibrillation by the 94 nurses in the sample and the heart rate recorded by
      simultaneous electrocardiographic (ECG) and plethysmographic (pleth) recordings.
      SUBJECTS: Nurses in four groups comprised the sample; registered nurses (N = 29),
      licensed practical nurses (N = 23), nursing students (N = 21), and registered
      nurses with advanced degrees who are clinical specialists and in faculty
      positions. RESULTS: The heart rate of the man varied from 57 to 111 beats/min
      (mean 81 beats/min). The mean absolute error rates for the six measurements
      ranged from 8 beats/min to 20 beats/min, all considered to be important when a
      10% error was used as the criteria for clinical significance. The apical method
      was significantly more accurate than the radial method regardless of whether the
      ECG or pleth standard was used (ECG--F1.90 = 72.91, p less than 0.0001; pleth-
      F1.144 = 4.68, p = 0.036). The 60-second counting interval was significantly more
      accurate regardless of the standard (ECG--F2.180 = 5.19, p = 0.006; pleth--F2.88
      = 3.95, p = 0.02). CONCLUSIONS: Atrial fibrillation occurs in 2% to 4% of people
      over 60 years of age and is one of the most difficult dysrhythmias to count.
      Accurate counts are important when making clinical decisions, yet measurement of
      heart rate in this study was quite inaccurate. The 60-second count and the apical
      method were the most accurate statistically, although differences in counting
      interval error rates were not clinically significant.

PMID- 1399663
TI  - Myocardial infarction size and scar dimensions: the influence of activity.
AB  - OBJECTIVE: The purpose of this study was to determine myocardial infarct size and
      scar dimensions in experimentally infarcted rats that were randomly assigned to a
      moderate, mild, or no exercise condition after infarction. DESIGN: Pretest
      posttest control group design (experimental). SUBJECTS: 57 male Harlan Sprague
      Dawley rats between 62 to 64 days of age and weighing 220 to 290 gm at the onset
      of the study. OUTCOME MEASURES: Infarction size, scar thickness, thinnest portion
      of scar. INTERVENTION: Mild exercise versus moderate exercise versus no exercise.
      RESULTS: No differences were found in infarct size, scar thickness, or thinnest
      portion of scar among the three groups. CONCLUSION: This study establishes that
      treadmill exercise, begun after an appropriate period of recovery, does not
      necessarily increase infarct size or scar thinning in the rat model. Further,
      animal and human studies are needed to fully explore the benefits and hazards of
      cardiac rehabilitation or exercise testing before or soon after discharge.

PMID- 1399662
TI  - Symptom distress in cardiac transplant candidates.
AB  - OBJECTIVE: To examine symptom frequency and distress in heart transplant
      candidates. DESIGN: Prospective, two-site study with a correlational design.
      SETTING: Large Midwestern and large Southern medical center. SAMPLE: Convenience
      sample of 175 adult patients (mean age 52 years, 85% men) awaiting heart
      transplantation. Fifty percent of the patients had ischemic cardiomyopathy and
      47% had dilated cardiomyopathy. INSTRUMENTS: The Heart Transplant Symptom
      Checklist (Grady, Jalowiec, & Grusk, 1988), a 92-item self-administered
      instrument that measures how much patients are bothered by symptoms on a four
      point rating scale, was developed by the research team for the study. Cronbach
      alpha reliability for the total scale was 0.95. RESULTS: The most frequent and
      distressing symptoms for patients awaiting heart transplantation were tiredness,
      difficulty breathing when walking or doing something, difficulty sleeping, and
      weakness in the whole body. Patients who had more symptom distress were unable to
      work. Higher symptom distress correlated significantly with higher stress, less
      life satisfaction, lower quality of life, and more functional disability.
      SUMMARY: Heart transplant candidates experience symptoms that may affect their
      ability to work and are associated with more functional disability and lower
      quality of life. IMPLICATIONS: Identification of the most frequent and
      distressing symptoms helps nurses and other health care providers to better
      assess and intervene with patients who are heart transplant candidates.

PMID- 1399664
TI  - Positioning effects on arterial oxygen and relative pulmonary shunt in patients
      receiving mechanical ventilation after CABG.
AB  - OBJECTIVE: To examine the effects of three different positions on arterial oxygen
      and relative pulmonary shunt in patients after coronary artery bypass graft
      (CABG) who are receiving mechanical ventilation with an effective tidal volume of
      15 ml/kg and a minimum of 5 cm H2O positive end-expiratory pressure. DESIGN:
      Repeated measures, counterbalanced. SETTING: Adult cardiovascular intensive care
      unit in a major tertiary referral hospital. SUBJECTS: Convenience sample of 30
      patients who had undergone CABG, 90% of whom had postoperative atelectasis.
      OUTCOME MEASURES: Partial pressure arterial oxygen (PaO2) and relative pulmonary
      shunt (areas of low ventilation-perfusion ratio). INTERVENTION: Supine, right
      lateral, and left lateral positions with head of bed elevated 30 degrees.
      RESULTS: No statistically significant differences in arterial oxygen and relative
      pulmonary shunt were found among the three positions. CONCLUSIONS: For a selected
      cohort, positioning may not be an important consideration in arterial oxygenation
      in patients who have undergone CABG and are receiving mechanical ventilation with
      a high tidal volume and positive end-expiratory pressure.

PMID- 1399666
TI  - The experience of dyspnea during weaning.
AB  - OBJECTIVE: To compare the degree of dyspnea experienced by ventilator-dependent
      patients receiving synchronized intermittent mandatory ventilation (SIMV) versus
      T-piece or pressure support ventilation (PSV) weaning. The relationship between
      self-reported perceptions of dyspnea and physiologic variables observed during
      weaning trials was examined. Variables included heart rate, respiratory rate,
      minute ventilation, and oxygen saturation as measured by a pulse oximeter.
      DESIGN: Quasi-experimental, counterbalanced design with repeated measures.
      SETTING: Medical intensive care unit of a large university-affiliated medical
      center. PATIENTS: Nine mechanically ventilated patients diagnosed with chronic
      obstructive lung disease. The patients were admitted for respiratory failure
      between May 1990 to November 1990. Six tolerated SIMV 4 versus T-piece trials;
      three were placed in the SIMV 8 versus PSV trials. PROCEDURE: Each patient's
      perception of dyspnea was measured using a visual analog scale (VAS) at the
      initiation and at 5-minute intervals of 20-minute weaning trials. Physiologic
      indicators were noted simultaneously with VAS ratings of dyspnea. RESULTS:
      Findings indicated no difference in the degree of dyspnea experienced between
      weaning methods compared. Within-subject regression analysis on VAS scores
      revealed individual differences in the relationship between physiologic
      indicators and perceptions of dyspnea. CONCLUSIONS: The patient's experience of
      dyspnea during the weaning process can be a valuable guide to observe the
      patient's progress. The VAS serves as a reliable, easy-to-use tool for
      quantifying the patient's perception of dyspnea.

PMID- 1399667
TI  - Infection control indicators in critical care settings.
AB  - The Joint Commission on Accreditation of Healthcare Organizations has developed
      and is currently testing eight infection control indicators in hundreds of
      hospitals. The indicator set focuses on surgical wound infections, postoperative
      pneumonia, use of urinary catheterization, ventilator-associated pneumonia,
      primary bloodstream infection, endometritis, adequacy of surveillance, and
      employee measles immunization. Critical care unit staff members may be involved
      in using indicator rates. Following the trend rates should suggest organizational
      systems and processes of care in critical care settings that may warrant further
      examination and improvement.

PMID- 1399665
TI  - The effect of positioning on arterial oxygenation in children with atelectasis
      after cardiac surgery.
AB  - OBJECTIVE: To determine the effect of body position on arterial oxygenation in
      children with unilateral atelectasis after cardiac surgery. DESIGN: Prospective,
      quasi-experimental, random assignment. SETTING: Midwestern university-affiliated
      tertiary pediatric medical center. PATIENTS: 25 children who underwent cardiac
      surgery and who presented with unilateral atelectasis within 2 weeks of
      operation. Age range was one month to 10 years (mean 34 months). OUTCOME
      MEASURES: The partial pressure of oxygen. INTERVENTION: Data collection was
      initiated within 24 hours of the diagnosed unilateral atelectasis. Arterial blood
      gases were drawn from intraarterial lines after subjects were placed for 15
      minutes in the supine, right lateral, and left lateral decubitus positions
      (atelectatic lung dependent or nondependent), the order being randomized.
      RESULTS: Analysis of variance for repeated measures was used in the data
      analysis. The mean PaO2 for the supine, nondependent, and dependent positions
      were 115, 118, and 112, respectively. No statistical differences at p less than
      0.05 level of significance were demonstrated for the body positions under study.
      Age and degree of atelectasis were analyzed as covariates to determine the
      possible correlation with the PaO2 and the change in PaO2. Age inversely
      correlated with the PaO2, r = -0.24 (p less than 0.05), indicating the older
      subjects had a lower PaO2. The degree of atelectasis demonstrated correlation
      with the change in PaO2, r = -0.26 (p less than 0.05) indicating the subjects
      with greater degree of atelectasis had a lesser change in PaO2. CONCLUSIONS:
      These results differ from similar studies on the effect of positioning in adult
      subjects. This finding suggests that the effect of positioning of children who
      have had cardiac surgery should be evaluated on an individual basis with close
      monitoring for changes in clinical condition and oxygen saturation and periodic
      arterial oxygen blood sampling until further studies can provide conclusive
      direction.

PMID- 1399668
TI  - The febrile response in critical care: state of the science.
AB  - Fever is a dynamic alteration in thermal balance caused by effects of pyrogens on
      the hypothalamic thermostatic set point. Thermoregulatory function remains intact
      during fever, but temperatures are maintained at higher levels. Shivering and
      vasoconstriction drive temperatures higher while causing physical exertion and
      distress to the patient. Biomedical research reveals potential benefits of fever,
      because fever-producing cytokines stimulate host defense responses. Nursing care
      is aimed at making rational decisions for comfort and energy conservation while
      maximizing the immune response. In this article the pathophysiologic process and
      benefits of fever are reviewed and a conceptual approach to nursing care based on
      knowledge of thermoregulatory responses is proposed. Nursing care measures
      include assessment of alterations in thermal balance, selection of appropriate
      measures to modify or support physiologic responses, and evaluation of outcomes
      of therapy. Research-based direction for care is presented, as well as gaps in
      scientific knowledge.

PMID- 1399669
TI  - Spotlight article: thrombolysis in unstable angina: randomized double-blind trial
      of t-PA and placebo. Circulation 1992;85: 150-7. (Freeman MR, Langer A, Wilson
      RF, Morgan CD, Armstrong PW.).
AB  - This is a well-written and executed study that indicates that infusion of t-PA in
      patients with unstable angina does not decrease in-hospital cardiac events and,
      in fact, may worsen myocardial perfusion. The small sample size requires further
      study replication.

PMID- 1399672
TI  - Infant home apnea documentation monitors.

PMID- 1399671
TI  - The long and the short of sinus arrhythmia.

PMID- 1399670
TI  - Hickman catheter Staphylococcus aureus bacteremia diagnosed by indium-111 scan.

PMID- 1399673
TI  - Issues in selecting and using apnea documentation systems.
AB  - The primary purpose of apnea monitoring is to ensure adequate warning of certain
      life-threatening respiratory and cardiac events, often in infants monitored at
      home. However, parents often become frustrated by frequent alarms, and other may
      not use the monitor at all. Unfortunately, ECRI has received a number of incident
      reports in which infants have died while not connected to their monitors or where
      a failure to monitor was suspected. We believe that some of these deaths may have
      been prevented if monitoring had been used properly. The most important step that
      parents can take to achieve effective monitoring is to faithfully follow the
      directions of their doctor. In an effort to ensure parental compliance,
      documentation capability has been added to many of today's monitors. In addition,
      those involved in providing patient care, especially the prescribing physicians,
      durable medical equipment (DME) providers, report scorers, interpreting
      physicians, and other clinicians, should carefully review their monitoring
      programs and the available documentation monitoring systems to determine how they
      can best meet their patients' needs. Below, we discuss the factors to consider
      when contemplating documented apnea monitoring and when selecting a documented
      monitoring system. The documentation features discussed are those we considered
      to be distinguishing factors among the systems evaluated in this issue and
      affected how we rated and ranked these units.

PMID- 1399674
TI  - The FDA Apnea Monitoring standard.

PMID- 1399675
TI  - Dislodging of rotor and improper sealing of cover lids on Baxter Medifuge C1700-2
      centrifuges.

PMID- 1399676
TI  - Corrosion of cast aluminum base on Century SL-10 (Saf-Lift) bath lift.

PMID- 1399677
TI  - Siemens Uroskop B2 urology table system.

PMID- 1399678
TI  - Nuclear Associates Miniscan densitometer.

PMID- 1399679
TI  - Air-Shields System V Model HRRM71-2 heart rate and respiration monitor.

PMID- 1399680
TI  - Use of ex vivo binding to measure the brain concentrations of putative
      radioligands.
AB  - The development of radioligands capable of imaging brain receptors depends on,
      amongst other factors, the ability of such compounds to penetrate the blood-brain
      barrier. We describe an ex vivo binding technique for measuring the brain
      concentration of peripherally administered unlabeled compounds. This technique
      can be used early in the development of putative radioligands. The
      pharmacokinetics of brain penetration of three muscarinic antagonists are
      described: QNB, BrQNB and the 2-thienyl derivative of BrQNB and were found to
      compare favorably to previous studies using [3H]QNB. These studies demonstrate
      the effectiveness of ex vivo binding in assessing the brain concentration of
      peripherally administered unlabeled compounds.

PMID- 1399681
TI  - Radiolabeled products in rat liver and serum after administration of antibody
      amide-DTPA-indium-111.
AB  - Anti-human serum albumin antibody (Ab) was used as a model antibody. Ab was
      conjugated with DTPA using cyclic DTPA dianhydride reaction and radiolabeled with
      111In. The labeled Ab was purified by affinity chromatography. Size exclusion
      HPLC of this product showed 62% of 111In bound to monomeric Ab and 38% of the
      activity bound to antibody oligomers with molecular weights ranging from 300,000
      to 450,000. The labeled antibody preparation was injected into the tail vein of
      rats. The radioactive substances in serum and the supernatant from liver
      homogenates were analyzed for molecular weight and immunoreactivity. Size
      exclusion HPLC of the serum samples indicated that the monomeric and dimeric Abs
      disappeared from the serum at a similar rate over a 48 h period. In addition, a
      new radioactive substance with an estimated molecular weight of 35,000 appeared
      in the serum. The immunoreactive fraction of the circulating 111In substances
      decreased slowly, somewhat proportional to the appearance of the metabolite. On
      the other hand, the immunoreactivity of the 111In substances in the supernatant
      from the liver homogenate decreased rapidly and no appreciable immunoreactivity
      was observed after 48 h. The labeled antibody was catabolized very rapidly in the
      liver and the major activity in the supernatant was associated with a small
      molecular weight metabolite which had a HPLC retention time identical to that of
      DTPA-111In. The second metabolite had an estimated molecular weight of 35,000. No
      radioactivity was associated with transferrin.

PMID- 1399683
TI  - Accumulation of radioactivity in the pancreas after intravenous administration of
      [13N]ammonia.
AB  - A biodistribution study of [13N]ammonia in rats showed a high accumulation of
      radioactivity in the pancreas soon after the intravenous injection of this
      tracer. In humans, the pancreas was also clearly visualized by dynamic positron
      emission tomography soon after the intravenous injection of [13N]ammonia. To
      investigate the mechanism of the pancreatic accumulation of [13N]ammonia, in
      vitro studies with pancreatic slices and in vivo biodistribution and metabolism
      studies were carried out in rats. The results indicated that [13N]ammonia enters
      the pancreas from the blood by diffusion at a rate dependent on local blood flow,
      and then is rapidly incorporated into the amino acid fraction (mainly the
      glutamine fraction), followed by its incorporation into protein. These findings
      suggest that [13N]ammonia could be useful for diagnostic imaging of the pancreas.

PMID- 1399682
TI  - Preparation of 123I-labeled 2'-iodospiperone and imaging of D2 dopamine receptors
      in the human brain using SPECT.
AB  - [123I]2'-ISP was readily prepared using a radioiodine exchange reaction with a
      radiochemical yield of approx. 50% after HPLC purification. The radiochemical
      purity of the product was more than 98% and the specific activity was 5.55-11.1
      GBq/mumol. Biodistribution studies performed in mice indicated that injection of
      [123I]2'-ISP with albumin produced a higher gastric uptake and a lower brain
      uptake than injection of the radioligand in a weakly acidic solution. In
      addition, toxicity tests performed in mice demonstrated that acute toxic effects
      would be very unlikely to be encountered if 2'-ISP was used for diagnostic
      purposes. A preliminary imaging study with [123I]2'-ISP in a healthy human
      volunteer showed its specific uptake by the basal ganglia, a region of the brain
      known to have a high density of D2 dopamine receptors.

PMID- 1399684
TI  - A simple method for producing a technetium-99m-labeled liposome which is stable
      in vivo.
AB  - A new method for labelling preformed liposomes with technetium-99m (99mTc) has
      been developed which is simple to perform and stable in vivo. Previous 99mTc
      liposome labels have had variable labeling efficiencies and stability. This
      method consistently achieves high labeling efficiencies (greater than 90%) with
      excellent stability. A commercially available radiopharmaceutical kit-
      hexamethylpropyleneamine oxime (HM-PAO)--is reconstituted with 99mTcO4- and then
      incubated with preformed liposomes that encapsulate glutathione. The incubation
      takes only 30 min at room temperature. Liposomes that co-encapsulate other
      proteins such as hemoglobin or albumin, in addition to glutathione, also label
      with high efficiency. Both in vitro and in vivo studies indicate good stability
      of this label. Rabbit images show significant spleen and liver uptake at 2 and 20
      h after liposome infusion without visualization of thyroid, stomach or bladder
      activity. This labeling method can be used to study the biodistribution of a wide
      variety of liposome preparations that are being tested as novel drug delivery
      systems. This method of labeling liposomes with 99mTc may also have applications
      in diagnostic imaging.

PMID- 1399685
TI  - Synthesis and biodistribution of a new radiotracer for in vivo labeling of
      serotonin uptake sites by PET, cis-N,N-[11C]dimethyl-3-(2',4'-dichlorophenyl)
      indanamine (cis-[11C]DDPI).
AB  - A new PET radiotracer for in vivo labeling of serotonin (5-HT) uptake sites, cis
      N,N-[11C]dimethyl-3-(2',4'-dichlorophenyl)-indanamine, cis-[11C]DDPI, was
      synthesized and its biological behavior was studied. The radiosynthesis of cis
      [11C]DDPI was performed by N-methylation of cis-N-methyl-3-(2',4'-dichlorophenyl)
      indanamine with [11C]iodomethane. The average radiochemical yield was approx. 8%,
      with an average specific activity of 600 mCi/mumol. Following intravenous
      administration, cis-[11C]DDPI accumulated in mouse brain regions rich in 5-HT
      uptake sites, such as olfactory tubercles, hypothalamus and frontal cortex.
      Following pre-injection of 1 mg/kg of paroxetine, a high affinity 5-HT uptake
      blocker, the binding of cis-[11C]DDPI in the olfactory tubercles, hypothalamus
      and frontal cortex was decreased by 23, 25 and 16%; this corresponds to 73, 82
      and 59% of the specific binding in these regions. These results suggest that the
      accumulation of cis-[11C]DDPI in the tissues rich in 5-HT sites is a result of
      specific binding of cis-[11C]DDPI to 5-HT uptake sites. Due to the relatively
      high non-specific uptake and slow clearance of this compound from non-specific
      binding sites, the ratio between specific and non-specific binding increased
      slowly with time, reaching 1.5:1 at 60 min after injection.

PMID- 1399686
TI  - [75Se]selenite and [75Se]selenate fluctuations during the development of murine
      hepatoma.
AB  - The distribution of selenate and selenite selenium in C57L/J mice during the
      progression of BW7756 murine hepatoma was investigated using intra-ocular
      injection with the oxyanions labeled with 75Se radioisotope. Comparison is made
      with the normal distribution of selenium studied by the RIXRF method. The trace
      elemental profiles, TEP, for the two oxidation states are compared in healthy and
      disease states. It has been found that the presence of tumor significantly
      changes the level of tracer in various uninvolved organs. These changes are
      prominent in the early growth phase of the tumor. The two oxidation states show
      differences in the TEP for kidney, spleen, stomach and testes.

PMID- 1399688
TI  - Specific biodetection of a murine spontaneous mammary carcinoma with labelled
      anti-human blood group-A monoclonal antibody.
AB  - The expression of cell surface antigens of the spontaneous transplantable M3
      murine tumour was studied by means of the monoclonal antibody (MAb) B2C114 which
      recognizes the human blood group-A carbohydrate antigen. Following
      radioiodination the MAb retained their immunoreactivity and demonstrated a
      significantly higher in vitro binding with isolated M3-tumour cells as compared
      with a control antibody. B2C114 revealed 10(6) antigenic sites per cell, with a
      constant affinity of 5.1 x 10(9)/M. Biodistribution studies showed that B2C114
      discriminated between malignant tumour and mouse normal tissues.
      Radioimmunodetection of Balb/c mice bearing s.c. M3-tumour showed that tumour was
      specifically defined without subtraction 1 day after injection of the
      radiolabelled antibody.

PMID- 1399687
TI  - Synthesis and evaluation of high affinity, aryl-substituted
      [18F]fluoropropylbenzamides for dopamine D-2 receptor studies.
AB  - The potent dopamine D-2 ligands (S)-2,3-dimethoxy-N-[(1-ethyl-2
      pyrrolidinyl)methyl]-5(3- [18F]fluoropropyl)benzamide (18F-1) and (S)-2,3
      dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3- [18F]fluoropropyl)-6
      hydroxybenzamide (18F-2) were prepared in high specific activity and 5-25%
      overall radiochemical yields. Benzamide 1 possessed a lower in vitro binding
      affinity for the D-2 receptor than salicylamide 2, but the in vivo striatal-to
      cerebellar radioactivity concentration ratios (St/Cb) in rats and dogs were
      nearly identical for the two compounds. Compound 18F-2 was more lipophilic than
      18F-1, and its increased penetration into and retention by striatal tissue was
      matched by an increase in non-specific binding in the cerebellum. Cerebral cortex
      radioactivity concentration levels in dogs were similar to cerebellum levels. The
      binding of 18F-labelled 1 and 2 displayed regional brain distribution patterns
      consistent with known dopamine D-2 receptor densities and was selectively blocked
      in the striatum of rats by dopamine D-2 antagonists. The binding of 18F-1 was
      found to be stereoselective, as the 18F-labelled (R)-enantiomer displayed no
      selective retention in the striatum of dogs. High levels of radioactivity were
      found in the bones of rats following the injection of 18F-1 and 18F-2, indicating
      that in vivo defluorination had occurred; however, no bone radioactivity was
      observed in dogs following the injection of these radioligands. Compound 18F-1
      was displaced from the striatum of dogs by both d-amphetamine-stimulated dopamine
      release and haloperidol at doses of 1 and 0.5 mg/kg, respectively, while compound
      18F-2 was displaced from the dog striatum only by haloperidol at these doses. The
      radioligand 18F-2 holds promise for positron emission tomography studies of the
      dopamine D-2 receptor system based upon its selective, potent binding and
      resistance to displacement by endogenous dopamine.

PMID- 1399690
TI  - 131I therapy in diffuse goiters: should we still use uptake free methods to
      calculate activities?

PMID- 1399691
TI  - Comparison of the biodistribution of 75Se- and 131I-labelled monoclonal
      antibodies in nude mice.
AB  - A monoclonal antibody, C-215, against colon cancer, was internally labelled with
      [75Se]methionine. The biodistribution was studied in tumour-bearing nude mice and
      compared with the biodistribution of [131I]C-215. The tissue uptake was divided
      into three parts: antibody bound to the antigen, antibody in the extracellular
      space and uptake of the released radionuclide. [75Se]C-215 showed a greater
      amount of antigen-bound antibody in the tumour, but also a greater unspecific
      uptake both in tumour and normal tissue.

PMID- 1399689
TI  - Synthesis and in vitro binding properties of halogenated analogues of GBR as new
      dopamine uptake carrier ligands.
AB  - We present the original synthesis of two halogenated analogues of the diphenyl
      piperazine GBR, bromo-GBR and iodo-GBR, as new dopamine uptake carrier ligands.
      The derivatives were purified by HPLC and chemically characterized. Bromo-GBR and
      iodo-GBR and iodo-GBR are potent inhibitors of [3H]GBR 12935 binding to rat
      striatal membrane, with Ki values of 116 and 113 nM, respectively. We prepared
      iodo-GBR labeled with iodide-125 from the brominated derivative and concluded
      that [123I]iodo-GBR could be a potential tool to explore the in vivo dopamine
      uptake carrier.

PMID- 1399692
TI  - A study of the concept of non-radioactive unit-dosed reagent kits [cold unit
      doses (CUDs)] as an efficient and cost-saving method for 99mTc
      radiopharmaceutical preparation.
AB  - Traditionally, when preparing 99mTc-labeled radiopharmaceuticals,
      [99mTc]pertechnetate is added to the entire contents of a vial of reagent kit,
      and patient doses are subsequently withdrawn from the vial. This technique of
      compounding can be potentially wasteful for two reasons: (1) once reconstituted
      with 99mTc, most reagent kits have a relatively short shelf-life, and thus the
      entire contents may not be used before expiration and (2) due to a need to
      conserve radioactivity in many hospitals, enough [99mTc]pertechnetate is added to
      the reagent kit in order to retrieve only 1-2 patient doses, even though adequate
      chemicals (ligand, reducing agent, etc.) are present in the reagent kit to supply
      as many as 5-10 doses. Hence, a method for optimizing the efficient use of
      reagent kits would be desirable. The purpose of this study was to determine the
      feasibility of unit-dosing non-radioactive reagent kits and storing these cold
      unit doses (CUDs) for eventual labeling with 99mTc. To evaluate this concept,
      unit doses were prepared from reagent kits of medronate (MDP) and pentetate
      (DTPA). The specific variables studied in this research were the effects of
      storage time, storage temperature and reconstitution volume (dilution) on the
      unit doses. These effects were monitored by measuring the radiochemical and
      biodistribution properties of the unit doses following their final reconstitution
      with [99mTc]pertechnetate. The labeling efficiency was determined using instant
      thin layer chromatograph (ITLC), and the biodistribution patterns of these
      radiolabeled CUDs were studied in mice. The results showed the MDP- and DTPA-CUDs
      stored at -18 degrees C retained the properties which resulted in acceptable
      radiochemical purity and biodistribution in mice for as long as 30 days. On the
      other hand, the radiochemical purity of MDP and DTPA unit doses stored at 25
      degrees C deteriorated rapidly. Mean radiochemical purities as low as 0.58-19.4%
      were observed on day 30. Altered biodistributions were observed in a manner
      consistent with the decreased labeling efficiencies. The CUDs of lower dilution
      (3 mL) appeared to be more stable than the CUDs of higher dilution (10 mL).
      However, the effect of reconstitution volume was much less significant than the
      temperature effect on the CUDs. In conclusion, the concept of unit-dosing non
      radioactive reagent kits appears to provide an efficient and cost-saving method
      for preparing infrequent and emergency radiopharmaceutical doses. The study also
      showed that the storage temperature of these unit doses is critical to the
      success of the procedure. The volume of reconstitution has a minimal impact on
      the stability of CUDs if stored at the appropriate temperature.

PMID- 1399693
TI  - In vivo studies of ethanol on prolactin and luteinizing hormone in rats and mice.
AB  - The interaction of ethanol (EtOH), prolactin (Prl) and luteinizing hormone (LH)
      was examined in two studies. In the first study, adult male C57B1/6J mice were
      given a single intraperitoneal injection of either vehicle or Prl at 5, 10 and 20
      mg/kg and a significant dose-related suppression of ethanol consumption was
      found. This injection did not cause any differences in food intake or body
      weight. Additionally, a 5 mg/kg dose of Prl was also given to adult male Long
      Evans Hooded rats and, similarly, there was a significant suppression of ethanol
      consumption. In a second study, when rats were given a free choice between water
      and 5% EtOH, three subgroups were found regarding the amount of EtOH consumption:
      low, medium and high. After 2 weeks of free choice, hypothalamic, but not serum
      Prl and LH levels, were significantly increased in EtOH-imbibing groups compared
      to controls. These findings suggest important interactions between EtOH
      consumption and ambient levels of Prl and LH.

PMID- 1399694
TI  - Preparation and biological behaviour of some neutral 99mTc-carbonyl
      dithiocarbamates showing rapid hepatobiliary excretion.
AB  - A simple procedure for the preparation of 99mTc-carbonyl complexes of
      dithiocarbamates in high yield and radiochemical purity has been developed and
      used for the preparation of 99mTc-carbonyl complexes of bis(2
      hydroxyethyl)dithiocarbamate and bis(2-hydroxypropyl)dithiocarbamate. These
      complexes were found to be extremely stable and their biological behaviour was
      studied in mice and compared to that of the 99mTcN- and the 99mTc-complexes
      [prepared by dithionite (dit) reduction] of the same ligands. The carbonyl
      complexes were found to be efficient hepatobiliary agents and cleared more
      rapidly than the corresponding 99mTcN- and 99mTc(dit)-complexes.

PMID- 1399695
TI  - Investigation of tumor metastatic potential with N-[18F]fluoroacetyl-D
      glucosamine.
AB  - In order to investigate the metastatic potential of tumors in vivo by measuring
      hyaluronic acid metabolism, C57BL/6 mice with B16 melanoma variants and C3H/He
      mice with FM3A tumor variants were evaluated using N-[18F]fluoroacetyl-D
      glucosamine (18F-GlcNFAc). The uptake of 18F-GlcNFAc was slightly higher (P less
      than 0.05) in B16-F10 tumors (high metastatic potential) than in B16-F1 (low
      metastatic potential). Analysis of metabolites showed that acid-insoluble
      fraction was the largest one in the liver by 60 min, whereas in the tumors,
      phosphates fraction was the major metabolite. Slower metabolism in tumors was
      suggested, and it may be one of the reasons for the difficulty of detecting the
      characteristics of their hyaluronic acid synthesis. 18F-GlcNFAc uptake by FM3A
      variants showed no significant correlation with their metastatic potential. In
      addition, N-acetyl-D-[1-14C]glucosamine, 2-deoxy-D-[1-14C]glucose and [6
      3H]thymidine failed to demonstrate any difference between tumors' metastatic
      variants in vivo.

PMID- 1399696
TI  - Development of a liposome-encapsulated radionuclide with preferential tumor
      accumulation--the choice of radionuclide and chelating ligand.
AB  - Various radionuclide-ligand complexes were encapsulated in liposomes and their
      accumulations in tumors were studied. Increased tumor accumulation was observed
      with every complex in the liposome-encapsulated form. However, different
      accumulation levels were registered for the various radionuclides even though
      they were all delivered using a similar liposome formulation. Though the
      liposomes remained intact in the circulation, they were degraded in the tumor,
      liver and spleen eventually. Thus, this suggests that tumor accumulation of
      liposome-encapsulated radionuclides is dependent on not only the in vivo behavior
      of the liposomes themselves, but also the characteristics of nuclide-ligand
      complexes after their release from liposomes. A correct choice of radionuclides
      and ligands for encapsulation in liposomes would enable excellent tumor-imaging
      agents to be achieved.

PMID- 1399697
TI  - 4-[123I]iodospiperone as a ligand for dopamine DA receptors: in vitro and in vivo
      experiments in a rat model.
AB  - Radioiodinated spiperone is of interest for dopamine (DA) receptor studies in the
      living human brain by single photon emission computed tomography (SPECT).
      Stimulated by data obtained with [11C]-N-methyl-spiperone we synthesized 4
      [123I]iodospiperone and investigated the in vitro binding characteristics of this
      ligand to the striatal membrane of the rat and the in vivo distribution over
      various rat brain regions. The in vitro binding experiments showed that this
      radioligand displays about 10 times less affinity for the DA receptor than
      spiperone and specific binding, as shown with [3H]spiperone, was not observed.
      Displacement by butaclamol was not observed. The in vivo studies demonstrated
      that both 4-[123I]iodospiperone and [3H]spiperone concentrate in striatal tissue,
      respectively, 1.9 and 3.5 times as high as in cerebellar tissue. Haloperidol
      pretreatment largely prevented this accumulation. In view of the obtained target
      to-non-target ratios we believe, however, that this accumulation in brain areas
      rich in DA-receptors does not offer prospects for clinical receptor imaging with
      SPECT.

PMID- 1399698
TI  - Selective localization of radioiodinated alkylphosphocholine derivatives in
      tumors.
AB  - We have designed and synthesized two radioiodinated analogs of
      hexadecylphosphocholine in order to evaluate their tumor imaging potential. 12
      (m[125I]iodophenyl)dodecyl phosphocholine (NM-324) and hexadecyl-2-[N,N-dimethyl
      N-(m[125I]iodobenzyl)-ammonium] ethyl phosphate (NM-326) demonstrated the ability
      of such compounds to localize in and thereby visualize the Walker 256 tumor in
      rats. However, the tumor avidity of NM-324 was far superior to NM-326. In
      addition, NM-324 showed excellent tumor localization in athymic mice bearing
      subcutaneous human tumors.

PMID- 1399699
TI  - Comparison of methods for incorporating a radioiodinated residualizing
      cholesteryl ester analog into low density lipoprotein.
AB  - Two different methods were evaluated for incorporating [125I]cholesteryl
      iopanoate ([125I]CI), a non-hydrolyzable cholesteryl ester analog, into LDL. The
      first procedure was an organic solvent delipidation-reconstitution procedure
      (R[125I-CI]LDL) while the second involved incubation of detergent (Tween-20)
      solubilized [125I]CI with whole plasma (D[125I-CI]LDL). R[125I-CI]LDL behaved
      similar to native LDL in vitro, but was markedly different in vivo, apparently
      due to a heterogeneity in particle size. D[125I-CI]LDL, however, was metabolized
      normally both in vitro and in vivo. These results, combined with the
      residualizing nature of [125I]CI, demonstrate that D[125I-CI]LDL is appropriate
      for tracing LDL uptake in vivo.

PMID- 1399700
TI  - The effect of ligand structure on glutathione-mediated decomposition of propylene
      amine oxime derivatives.
AB  - Tetramethylpropyleneamine oxime (TMPAO) was synthesized and complexed to 99mTc.
      99mTc-TMPAO samples, when challenged with reduced glutathione (GSH), were shown
      to have two GSH sensitive components, similar to a mixture of d,l and meso 99mTc
      HMPAO. One component had a GSH-induced second-order dissociation rate constant
      (K2) similar to 99mTc-meso-HMPAO. Despite the presence of a large fraction of
      this component in these samples, brain uptake and autoradiographic studies with
      99mTc-TMPAO were equivalent to 99mTc-d,l-HMPAO suggesting that both the d,l and
      meso 99mTc-TMPAO isomers are efficiently trapped in brain.

PMID- 1399701
TI  - Synthesis, characterization and biodistribution studies of a neutral-lipophilic
      Tc-99m N3S2 chelate.
AB  - Diaminedithiols (DADT) are known to form neutral-lipophilic complexes with 99mTc
      in aqueous solutions, where they are readily formed in high yields and
      demonstrate excellent stability. A new triaminedithiol (TADT) ligand was
      synthesized, characterized and shown to form a neutral-lipophilic 99mTc-chelate.
      The biodistribution of this 99mTc chelate in rats showed that its uptake in brain
      or heart following i.v. injection of the 99mTc chelate was low, but activity
      taken up was retained over a long period of time. The in vivo and in vitro
      properties of this chelate indicate the possibility that chemical modification of
      this TADT ligand may produce ligand systems that form 99mTc chelates with
      suitable diagnostic properties.

PMID- 1399703
TI  - RecA-like strand-transfer activity at the meiotic prophase in Bombyx mori.
AB  - An ATP-independent strand-transfer activity has been identified in nuclear
      extracts prepared from Drosophila tissue culture cells and isolated nuclei from
      Bombyx testes. Extraction of the activity from testes at larval stages where the
      majority of the cells were in meiotic prophase was only possible when the
      chromosome scaffold/synaptonemal complex was dissolved by addition of high
      concentrations of DTT (80 mM). No cross reaction was detected when partly
      purified extracts were assayed with antibodies against E. coli RecA protein.

PMID- 1399702
TI  - Evaluation of 99mTc-erythromycin and 99mTc-streptomycin sulphate for the
      visualization of inflammatory lesions.
AB  - 99mTc-erythromycin (E) and 99mTc-streptomycin sulphate (SS) were prepared with
      greater than 98% labelling efficiency. The labels were stable up to 24 h of
      testing, using ITLC-SG strips and acetone and saline as solvents. The
      biodistributions of both radiopharmaceuticals versus 67Ga-citrate were studied in
      mice with turpentine-induced abscesses at 6 days post-induction. The mice were
      sacrificed at 1, 3 and 6 h post-injection of 15 MBq of 99mTc-E or 99mTc-SS. Mice
      injected with 67Ga-citrate were sacrificed at 4 and 24 h. The maximum abscess-to
      muscle ratios obtained by biodistribution studies were 2.36 +/- 1.04 (6 h), 2.38
      +/- 0.38 (6 h) and 4.76 +/- 2.04 (4 h) with 99mTc-E, 99mTc-SS and 67Ga-citrate,
      respectively. The maximum abscess-to-contralateral tissue ratios by ROIs over
      respective areas on scintigrams were 2.38 +/- 0.16 (6 h), 3.21 +/- 0.14 (3 h) and
      3.24 +/- 0.92 (24 h) for 99mTc-E, 99mTc-SS and 67Ga-citrate, respectively. The
      uptake mechanism might be infiltration into interstitial space due to increased
      capillary permeability.

PMID- 1399704
TI  - Stillborns, partially monosomic and partially trisomic, in the offspring of a
      boar carrying a translocation: rcp(14;15)(q29;q24).
AB  - Smaller liters and an increased rate of stillbirth were observed among the
      offspring of a boar carrying a reciprocal translocation, rcp(14;15)(q29;q24). The
      translocation appeared to be of de novo origin since, according to the owner, the
      sire and dam of the proband boar both produced normal-sized litters and no
      stillbirths. The increased rate of stillbirth among offspring of the proband was
      due to the production of zygotes partially monosomic for chromosome 14 (14q29
      qter) and partially trisomic for chromosome 15 (15q24----qter). Three out of 4
      such stillborn piglets had a cleft palate. One of the 4 also had a cardiac septal
      defect. Two partially monosomic and partially trisomic foetuses recovered at 95
      days' pregnancy appeared patho-anatomically normal. The smaller litters were
      assumed to be due to an early wastage of embryos having other types of unbalanced
      karyotypes caused by the reciprocal translocation.

PMID- 1399705
TI  - Localization of the citrate synthase (CS) gene to the p12-p13 bands of chromosome
      5 in pigs by in situ hybridization.
AB  - Citrate synthase (CS) is a key enzyme of the Krebs tricarboxylic acid cycle. A
      1.4 kb porcine CS cDNA probe was used to chromosomally localize the CS gene in
      pigs by in situ hybridization. Two in situ hybridization experiments were
      conducted. Although the first experiment indicated a distinct signal on the 5p12
      p13 bands, a secondary signal was observed on the 13q24-q32 bands. Hence, a
      second in situ hybridization experiment was conducted at higher stringency. The
      results demonstrated a consistent signal on the 5p12-p13 bands, and the signal on
      chromosome 13 was scattered with no prominent secondary peak. The CS gene was
      therefore assigned to the p12-p13 bands of chromosome 5 in pigs.

PMID- 1399706
TI  - Cytochrome-b sequence variation among parrots.
AB  - The nucleotide sequence of a 307 bp fragment of the mitochondrial cytochrome-b
      gene was determined for 12 species of parrot, using the polymerase chain reaction
      and direct sequencing. Sequence divergence ranged from 26-54 differences in
      pairwise comparisons, with the majority of base substitutions occurring at third
      positions of codons. The transition:transversion ratio was determined to be
      higher (approximately 24.3:1) in recently divergent parrot lineages than has
      generally been observed in other groups. Strongly biased base composition,
      particularly at the third position of codons, is evident among the sequences.
      Phylogenetic relationships among more divergent taxa were estimated, using only
      transversion substitutions, while all the substitutions were useful for closely
      related taxa. The African genera Psittacus and Poicephalus are closely related,
      in contrast to the Australian genera Nymphicus, Purpureicephalus and
      Melopsittacus, which represent more divergent lineages. The cockatoos appear to
      represent an ancient lineage within the parrots.

PMID- 1399707
TI  - Localization of the 6-phosphogluconate dehydrogenase (PGD) gene in horses by in
      situ hybridization.

PMID- 1399709
TI  - [Preventive examination for noise-induced hearing loss in accordance with the new
      regulation 20].
AB  - The regulations for the testing and prevention of noise-induced hearing loss in
      German industry since 1974 are summarized. Current testing involves both speech
      and impedance audiometry. While initials studies will be directed through
      occupational medicine, definitive managements will be provided by
      otolaryngologists involved in the prevention program.

PMID- 1399708
TI  - High-resolution GTG-banding of chromosomes in the swamp buffalo (Bubalus bubalis
      L.): description of chromosome 1.

PMID- 1399710
TI  - [Clinical aspects and therapy of skin malignancies in the head and neck area].
AB  - A retrospective study of 199 surgically treated skin carcinomas showed that the
      majority of the insufficiently resected tumors had a maximum diameter of 10 mm. A
      surgical concept is presented which allows reliable histological control of the
      tumor margins and an exact resection of any residual carcinoma. This therapeutic
      approach is also indicated in the management of small skin malignancies.

PMID- 1399711
TI  - [Diagnosis and differential diagnosis of squamous epithelial metaplasia in the
      parotid gland].
AB  - The authors report a case of proliferating squamous epithelium in the necrotic
      edge of multifocal oncocytic adenomatous hyperplasia of the parotid gland. A
      correct histological diagnosis is of great clinical relevance and difficulty,
      since similar findings can occur in mucoepidermoid carcinoma. The various cell
      types in the parotid gland and their roles in neoplasia are discussed.

PMID- 1399713
TI  - [Psychosomatic findings in patients with contact granuloma--initial results].
AB  - In a prospective study, 33 patients with vocal cord granulomas were seen in a
      psychosomatic interview and given questionnaires. Results showed the significance
      of psychosomatic factors in the occurrence of vocal cord granulomas. Psycho
      social stress situations, particularly in private lives, and losses of
      emotionally significant persons were of prime importance. Two types of
      personalities--a narcissistic and a psychosomatic type--were represented about
      equally. In the personality structure of the patients, compulsive behavior was
      diagnosed most frequently while depressive features occurred to a lesser degree.
      Supportive and expressive psychotherapy was indicated in two thirds of the cases.

PMID- 1399712
TI  - [The value of nuclear magnetic resonance tomography in tumor staging of laryngeal
      /hypopharyngeal cancer].
AB  - Twenty-four patients with tumors of the larynx and hypopharynx were examined with
      magnetic resonance imaging (MRI) and laryngoscopy. The results of MRI and
      laryngoscopy were then correlated with the pathology reports. Diagnostic findings
      of 84% of the MRI studies correlated with the pathology report, while
      laryngoscopy provided exact classification in 79%. MRI tended to overestimate
      tumor size because edema or inflammatory reactions of surrounding tissues
      simulated tumors. However, normal mucosa also enhanced contrast medium,
      restricting the value of this technique. Laryngoscopy tended to underestimate
      tumor size, because deep extensions of tumor and cartilage involvement were
      difficult to detect. Nonetheless, the utility of MRI in obtaining axial, coronal
      and sagittal slices was found to facilitate the preoperative staging of tumor
      extensions.

PMID- 1399714
TI  - [Language development disorders--studies of preschool children of the Leipzig
      special language school].
AB  - Children with severe speech disorders were examined to determine the causes of
      their abnormal speech development. Thirty-seven preschool and school-age children
      were followed up and results compared. All children had low intelligence
      quotients, with most of the children coming from low social backgrounds. However,
      both of these factors (intelligence and low social background) had no influence
      on the improvement of speech levels after therapy. Two-thirds of the children
      with moderate conductive hearing losses showed improvement after therapy, so that
      the effect of this hearing loss was believed to be a significant cause for the
      development of speech disorders. An early evaluation must be performed by a
      qualified phoniatrican or pediatric audiologist when children are 1.5 years old
      and are not able to construct words.

PMID- 1399715
TI  - [Echinococcosis of the temporal bone--epidemiology, diagnosis, therapy and review
      of the literature].
AB  - A case of primary echinococcosis or hydatid disease of the temporal bone is
      reported in which no other organ system was involved. Epidemiology, diagnostic
      problems, clinical findings and therapy in relationship to the available
      literature are reviewed. In the patient described, complete surgical removal of
      the parasitic cysts was required as well as chemotherapy with Mebendazole.

PMID- 1399716
TI  - [Squamous cell cancer of the larynx after exposure to tar vapor--a case report].
AB  - The following case report describes the development of laryngeal cancer of a non
      smoker exposed to tar-emissions due to working with asphalt. Additionally, a
      basal cell carcinoma in the face caused by tar-emission underlines the role of
      this risk factor in the development of cancer in the head and neck.

PMID- 1399717
TI  - The 1991 Nomenclature Report.

PMID- 1399718
TI  - Nomenclature 1991 foreword.

PMID- 1399719
TI  - Molecular analysis of HLA-DRB1*08/12 alleles: identification of two additional
      alleles.
AB  - A nonradioactive oligotyping method that takes advantage of selective
      amplification using the polymerase chain reaction (PCR) and oligonucleotide probe
      hybridization was developed to distinguish all reported HLA-DRB1*08/12 alleles.
      Selective amplification was achieved using a primer complementary to the sequence
      encoding YSTGECY at positions 10-16 in the first hyperpolymorphic region (HPMR).
      This selective amplification of the HLA-DRB1*08/12 subset of alleles provides a
      refinement in HLA oligotyping that permits unambiguous oligotyping of many
      heterozygotes that cannot be resolved using less selective amplification
      alternatives. The amplified DNA was hybridized with a panel of then digoxigenin
      labeled probes to resolve oligotypes that correspond to all reported HLA
      DRB1*08/12 alleles. Oligotyping of HLA-DRB1*08/12 samples revealed two previously
      unknown HLA-DRB alleles. One allele, DRB1*0805, differs from DRB1*0801 by a
      leucine to alanine substitution at position 74. This allele is of particular
      interest because it is very similar to HLA-DRB1*08 alleles (YSTGECY and lack of
      an associated HLA-DRB3 gene), but it lacks leucine at position 74, which is
      characteristic of all previously reported DRB1*08 alleles. The second HLA-DRB1*08
      allele, DRB1*0804, differs from DRB1*0802 by a glycine to valine substitution at
      position 86.

PMID- 1399720
TI  - HIV envelope protein is recognized as an alloantigen by human DR-specific
      alloreactive T cells.
AB  - Recent studies from this laboratory reported the mapping of the full profile of T
      cell allorecognition regions of HLA-DR2 beta subunit. The results indicated the
      presence of an allodeterminant within DR2 beta regions 141-156. In another study,
      we have shown that this allodeterminant is one of five regions of structural
      homology between the DR2 beta molecule and the HIV-envelope protein gp120 region
      254-268. The fact that gp120 peptide 254-268 is homologous to the allodeterminant
      within the DR2 beta region 141-156 prompted us to investigate whether synthetic
      gp120 peptide 254-272 is recognized by human DR2-specific alloreactive T-cell
      lines. Five human alloreactive T-cell lines were prepared that were specific for
      the DR2 molecule and did not recognize DR1. These lines mounted in vitro
      proliferative responses to the allodeterminant peptide DR141-156 and also
      responded to the DR-similar peptide gp254-272. Removal of the residues 262-272
      from the gp120 peptide (i.e., peptide 254-263) resulted in essentially complete
      loss of its proliferative activity. The effect of deletion of three residues of
      homology (Val-Val-Ser) at the N terminal (i.e., peptides DR145-156 and gp257-272)
      was examined. Peptide DR2 beta 145-156 exhibited very low stimulating activity,
      whereas peptide gp 257-272 did not cause T-cell proliferative responses in any of
      the alloreactive T-cell lines. The T-cell lines did not respond to unrelated
      peptide controls, thus further confirming the specificity of these responses.
      These findings indicate that the virus is recognized as an alloantigen by human
      alloreactive DR2-specific T cells.

PMID- 1399721
TI  - Nomenclature for factors of the HLA system, 1991.

PMID- 1399722
TI  - HLA DQA, DQB, and DRB genotyping by oligonucleotide analysis: distribution of
      alleles and haplotypes in British caucasoids.
AB  - A precise method for comprehensive HLA DQA and DQB genotyping using gene
      amplification and hybridization with sequence-specific oligonucleotide (SSO)
      probes is described. Twenty-four SSO probes were used to detect all DQ allotypes
      defined by nucleotide sequence variation in the second exons of the DQ genes,
      using a standard set of conditions for all probes at each locus. Five hundred
      individuals were genotyped for 8 DQA1 and 16 DQB1 alleles by using this method
      and for 33 alleles of the DRB1, DRB3, DRB4, and DRB5 genes by using previously
      described SSO probes. The 4-locus DQB1-DQA1-DRB1-DRB3/4/5 haplotypes present were
      characterized on the basis of known linkage disequilibrium between class II
      alleles. Fifty-two different haplotypes that have previously been described were
      further characterized at the nucleotide sequence level and two novel haplotypes
      were identified. The distributions of these alleles and haplotypes in 177
      randomly selected healthy Caucasoid controls from the United Kingdom are
      reported. These results identify further haplotypic diversity in the HLA class II
      region, even though strong linkage disequilibrium exists between the DR and DQ
      gene loci.

PMID- 1399723
TI  - The clinical significance of a positive post-irradiation prostatic biopsy without
      metastases.
AB  - To define the prognostic value of a post-irradiation prostatic biopsy, the
      outcome of 203 previously irradiated patients who underwent post-treatment biopsy
      was analyzed. The majority of patients were selected for biopsy based on an
      abnormal digital rectal exam or elevated prostate specific antigen. Patients with
      distant metastases found at the time of biopsy were excluded from further
      analysis. One hundred thirty-nine (139) of these had a positive biopsy and 64
      were negative. Those with a positive biopsy tended to present with more locally
      advanced (Stage B2/C) tumors (61%) compared to those with negative biopsies
      (42%). The 10- and 15-year survival and cause-specific survival from the time of
      initial presentation were similar for both groups. However, those with a negative
      biopsy had a more favorable survival and cause-specific survival from the time of
      post-treatment biopsy and were less likely to develop distant metastases than the
      positive biopsy group. These data suggest that a positive prostatic biopsy is
      associated with a greater likelihood of subsequent distant relapse and decreased
      survival following biopsy relative to patients with negative biopsies. Since a
      positive post-treatment biopsy is more likely among patients presenting with
      locally-advanced disease, perhaps more aggressive initial therapy (i.e.,
      interstitial boost or hyperthermia) would benefit this subgroup.

PMID- 1399724
TI  - The significance of post-irradiation prostate biopsy with long-term follow-up.
AB  - Ninety-four patients, Stage A2-C, definitively irradiated for adenocarcinoma of
      the prostate from 1975 to 1981 underwent digitally directed transperineal needle
      biopsy of a clinically negative prostate gland at least 18 months post-therapy.
      Ten of 55 patients (18%) treated with Iodine-125 implantation and 7 of 39
      patients (18%) externally irradiated were found to have positive biopsy
      specimens. Overall, clinical local failure occurred in 53% of patients with
      positive biopsy results but in only 18% with negative specimens, p = .006. The
      false negative biopsy rate in patients treated with I-125 was nearly three times
      that for external beam, 24% versus 9%, perhaps because of the greater possibility
      of inhomogeneous dose distribution with I-125, allowing for a higher degree of
      sampling error. Actuarial local failure at 5 years was 44% versus 8% with
      positive and negative biopsies, respectively, and 75% versus 24% at 10 years (p =
      .0001). The distant metastatic rate was twice as high in biopsy-positive as
      compared to biopsy-negative patients, 71% versus 35%, p = .015. Actuarially, only
      19% of patients with a positive biopsy are NED at 10 years as compared to 62% of
      those with a negative biopsy (p = .0001). PSA values are supportive in those
      patients thought to be disease-free. The incidence of positive biopsy and
      associated local recurrence are in keeping with clinical treatment failure rates
      as reported in multiple studies to date.

PMID- 1399725
TI  - External beam radiotherapy for incidental adenocarcinoma of the prostate
      discovered at transurethral resection.
AB  - This paper updates the results of 89 patients treated between 1967 and 1989 for
      incidental carcinoma discovered at transurethral resection of the prostate
      (Stanford stage T0 or AJC-UICC stage T1) with external beam irradiation. Twenty
      two patients had Stanford T0 focal (less than 5% involvement of the prostatic
      chips) and 67 presented with Stanford T0 diffuse (5% or more involvement). Follow
      up ranges from 4 months to 25.1 years, with a mean follow-up of 9.8 years. The
      actuarial local control for Stanford T0 focal is 100%, and 70% for Stanford T0
      diffuse at 15 years. There was no difference in survival between Stanford T0
      diffuse and T0 focal and the expected survival of an age-matched control
      population. Patients who were treated when younger than 65 had a similar local
      control and distant relapse when compared to those treated when 65 or older.
      There was no difference in local control, freedom from relapse, or disease
      specific survival when the 38 patients who received irradiation to the prostate
      only are compared with the 29 who also received pelvic irradiation for Stanford
      T0 diffuse carcinoma. Patients with a Gleason score of 6 or more, when compared
      with those with a score of 5 or less, experienced more distant relapses and
      similar local control, suggesting that patients with a high grade tumor have
      occult metastases at presentation.

PMID- 1399726
TI  - Prognostic significance of pelvic recurrence and distant metastasis in prostate
      carcinoma following definitive radiotherapy.
AB  - This report is a retrospective analysis of 317 patients with recurrent prostate
      carcinoma, following definitive radiation therapy to 738 patients with
      histologically confirmed, clinical Stage T1b-T4(A2-D1) adenocarcinoma of the
      prostate. Seventy-four patients (10%) experienced pelvic recurrence only; 100
      (13%) both pelvic recurrence and distant metastasis, while 143 (20%) developed
      distant metastasis only. The diagnosis of prostate recurrence was histologically
      confirmed in 92/174 (53%), while in the others diagnosis was based on clinical
      and radiographic evidence. Ninety percent of all recurrences occurred within 7
      years of initial treatment. The median survival from time of recurrence for all
      patients was 27 months, with 5-, 8-, and 10-year survival rates of 24%, 12%, and
      7%, respectively. In patients who experienced pelvic recurrence only, the 5-, 8-,
      and 10-year survival rates were 50%, 30%, and 22%, respectively (p < 0.0001). The
      5-year survival rate from time of recurrence for patients who experienced pelvic
      recurrence with initial Stage T1b(A2) and T2(B) disease was 71% as opposed to 39%
      for patients with initial Stage T3(C) disease. The time of recurrence (i.e., the
      disease-free interval from initial treatment) significantly affected subsequent
      survival: the 5-year survival rates from time of recurrence for patients with
      pelvic recurrence were 20%, 49%, and 94% for those who recurred within 2 years, 2
      to 5 years, and more than 5 years, respectively. Two-thirds of the patients with
      recurrence received hormonal therapy, including bilateral orchiectomy. Salvage
      therapy with hormones, including bilateral orchiectomy, has a favorable impact on
      patient survival: The 5-year survival rate from time of pelvic recurrence
      salvaged with hormones was 70% compared with 21% for patients not receiving
      hormonal therapy. In conclusion, the prognostic factors that affect subsequent
      patient survival after pelvic recurrence include initial stage, disease-free
      interval from initial treatment, and salvage therapy with hormones. Patients with
      distant metastasis with or without pelvic recurrence showed statistically worse
      survival and were apparently not influenced by initial tumor stage, or disease
      free interval from initial treatment.

PMID- 1399728
TI  - Radiotherapy for prostate cancer: should the seminal vesicles be considered
      target?
AB  - During radiotherapy for prostate cancer, the ability to predict occult seminal
      vesicle invasion is important since irradiation of the entire seminal vesicles
      necessitates enlarging the radiation fields beyond what is usually used to
      irradiate the prostate gland alone. We analyzed the records of 302 patients with
      clinical Stage T1 or T2 adenocarcinoma of the prostate treated with radical
      surgery at Duke University Medical Center between 1970 and 1983. Univariate and
      multivariate analyses were used to examine the relationship between the risk of
      occult seminal vesicle involvement (defined herein as histologic involvement of
      the seminal vesicles not detected by physical or radiologic examination) and the
      following factors: histologic grade, age, clinical stage, and preoperative acid
      phosphatase. Among 249 patients with complete information, increasing histologic
      grade (p < 0.001) and clinical stage (p < 0.04) were found to be the strongest
      predictors of occult seminal vesicle invasion. Conversely, seminal vesicle
      invasion was very unusual in well-differentiated T1-T2 tumors (6%). This low risk
      group represented 28% (70/249) of this patient population. There appears to be a
      substantial subset of patients with well differentiated T1 or T2 tumors who are
      at very low risk for occult seminal vesicle involvement and in whom the seminal
      vesicles can be excluded from the target volume. The reduction in target volume
      may reduce normal tissue reactions, facilitate dose escalation, and possibly
      increase local control rates.

PMID- 1399727
TI  - Nuclear roundness factor and local failure from definitive radiation therapy for
      prostatic carcinoma.
AB  - Of 375 patients with prostatic carcinoma treated definitively with radiation
      therapy at this institution with at least a 5 year follow-up, 23 patients failed
      locally only, 72 failed with distant metastasis only, 60 had both local and
      distant failure, while 220 showed no evidence of disease. In search for a
      possible marker for local failure following radiation therapy, we examined
      several nuclear morphometric parameters which have been shown to correlate with
      the biologic aggressiveness of this disease. The 23 locally failed only patients
      were matched with 23 no evidence of disease patients for stage, grade, treatment
      modality, prior surgery, age at diagnosis and race. Archival hematoxylin and
      eosin slides were obtained for 22 of the 23 matched pairs, and morphometric
      features, including nuclear roundness factor and nuclear area, as well as numbers
      of nucleoli were assessed using computer-assisted image analysis in both tumor
      cells and normal prostatic epithelium. Tumor nuclei from the locally failed only
      patients had significantly higher nuclear roundness factor values (p = 0.0089)
      compared with tumor cells from no evidence of disease patients. Analysis of these
      data by clinical stage demonstrated no significant differences between the
      locally failed only and no evidence of disease patients. Likewise, there were no
      significant differences in nuclear roundness factor values of locally failed only
      and no evidence of disease patients with poorly or moderately well-differentiated
      tumors. However, there was a highly significant difference (p = 0.0012) in the
      nuclear roundness factor values of locally failed only and no evidence of disease
      patients with well-differentiated tumors. Thus, there appears to be a subset of
      patients with well-differentiated adenocarcinoma of the prostate who have
      significantly more irregular tumor nuclei and who fail locally only following
      definitive radiation therapy.

PMID- 1399729
TI  - The prognostic significance of race and survival from prostate cancer based on
      patients irradiated on Radiation Therapy Oncology Group protocols (1976-1985).
AB  - A number of studies have identified race as a prognostic factor for survival from
      prostate cancer. To evaluate the prognostic significance of race in a controlled
      setting, we evaluated 1294 patients treated on three prospective randomized
      trials conducted by the Radiation Therapy Oncology Group between 1976 to 1985.
      One-hundred and twenty (9%) of the patients were coded as black, while 1077 (83%)
      of the patients were coded as white. Protocol 7506 included 607 patients with
      clinical Stage T3-T4Nx or T1b-T2N1-2. Protocol 7706 included 484 patients with
      clinical Stage T1b or T2 who were node negative. Protocol 8307 included 203 Stage
      T2b-T4 patients with no lymph node involvement beyond the pelvis. Univariate and
      multivariate analyses were used to assess the possible independent significance
      of race and other prognostic factors, including Gleason score, serum acid
      phosphatase, nodal status, and hormonal status. Protocols 7706 and 8307 revealed
      that race was not of prognostic significance for disease-free or overall survival
      by either univariate or multivariate analysis. Univariate analysis of Protocol
      7506 revealed that the median survival for blacks was somewhat shorter (5.4 years
      vs. 7.1 years, p = 0.02). This difference persisted after a multivariate
      analysis. A higher percentage of blacks treated on 7506 had an abnormally
      elevated serum acid phosphatase compared to whites (p = 0.006), and the time to
      distant failure tended to be shorter (p = 0.07). These findings suggest that
      blacks treated on 7506 may have had more extensive disease at presentation. Based
      on these prospective randomized trials, it is most likely that the lower survival
      noted for black Americans with prostate cancer reflects the tendency for blacks
      to present with more advanced disease. Differences in access to care, the quality
      of care received, and the impact of co-morbid conditions may explain the lower
      survival reported for black Americans elsewhere in the literature.

PMID- 1399730
TI  - High grade adenocarcinoma of prostate in smokers of ethnic minority groups and
      Caribbean Island immigrants.
AB  - The degree of differentiation of 670 blacks and white patients treated from 1980
      1990 for curative and palliative external beam radiation therapy and surgery at
      State University of New York Health Science Center at Brooklyn and Kings County
      Hospital were analyzed retrospectively, stratified according to race, age,
      smoking, and grade. In addition stage, birth place and median survival were also
      analyzed. Overall mean age was 69 years (Std. Dev. 8.97). 69% were blacks and
      27.8% were whites. 65.4% were smokers and 34.6% were non-smokers. Smokers had
      high incidence of more invasive and high grade adenocarcinoma of prostate (p < or
      = 0.00005) compared to control group (non-smokers with prostate carcinoma).
      Statistically significant difference was found in the degree of differentiation
      of carcinoma of prostate in smokers compared to non-smokers. Smokers had 15.04%
      well, 27.07% moderate, and 57.89% poorly differentiated adenocarcinoma compared
      to non-smokers in which 37.1% were well, 45.16% moderate, and 17.74% poorly
      differentiated cancer of prostate (p < or = 0.00005). Sixty-three percent blacks
      and 40.16% whites had Stage D cancer (p < or = 0.00005). 68.3% smokers and 53.3%
      non-smokers had Stage D cancer (p = 0.01). Overall median survival for blacks was
      74.04 months compared to whites of 115.73 months (p < or = 0.00005).

PMID- 1399731
TI  - Combined pre- and postoperative adjuvant radiation therapy for bladder cancer--a
      ten year experience.
AB  - From 1978 through 1987, 78 patients with carcinoma of the bladder were treated
      with combined pre- and postoperative adjuvant radiation therapy. All were given a
      single dose of pre-operative radiation therapy, 500 cGy, either on the day of or
      the day before cystectomy. Histological staging on the cystectomy specimens
      according to the TNM classification system was performed. Forty patients with
      Stage P2 (high grade III and IV), P3A, P3B, P4A, or N+ underwent planned high
      dose postoperative radiation therapy (4000-4500 cGy) in 5 weeks. The whole pelvis
      was treated with conventional fractionation of 180 cGy 5 days per week. Median
      follow-up was 52 months, with 36 months minimum follow-up. There was a 67%
      overall 5-year survival, and those with P1 and P2 (Grade I and II) had an 84% 5
      year survival. Survival for patients with P2 tumor (Grade III and IV), P3A, P3B,
      and P4/N+ stages was 57%, 56%, 39%, and 50%, respectively. Bowel obstructions
      developed in 8% of patients who received no postoperative radiation therapy and
      37% in those who did. Genitourinary complication rates were similar in both
      groups, 13% in the group that received no postoperative radiation therapy and 10%
      in the group that did. Although the planned approach of combined pre- and
      postoperative radiation therapy for unfavorable stages of bladder cancer is
      associated with a better than 50% 5-year survival rate (except in Stage P3B
      cancer), the bowel toxicity was unacceptably high.

PMID- 1399733
TI  - Iridium-192 interstitial therapy for squamous cell carcinoma of the penis.
AB  - From February 1971 through February 1989, 51 patients with biopsy proven
      epidermoid carcinoma of the penis were treated with interstitial therapy (Iridium
      192). The breakdown according to the stage was T1s = 3, T1 = 14, T2 = 28, T3 = 6,
      N0 = 43, N1 = 7, N2 = 1. The dose ranged from 50 to 65 Gy (mean: 60 Gy). Patients
      without clinical nodal involvement received no treatment to the nodes. Stage N1
      and N2 patients had surgery and external irradiation to the inguinal and iliac
      nodes. Six of fifty-one (12%) patients developed nodal and/or metastatic disease
      following therapy. Five of six presented initially with clinical nodal
      involvement. Seven of fifty-one (14%) developed local recurrence only, requiring
      surgery (four partial penectomies, three total penectomies). Six of these seven
      patients are alive and free of disease with a mean follow-up of 5.5 years. Nine
      of thirty eight (23%) patients with local control developed local necrosis. The
      treatment consisted of local excision (one patient), partial amputation (six
      patients) or total amputation (two patients). Partial urethral stenosis was noted
      in 17/38 (45%) of the patients. Foreskin sclerosis occurred in 3/38 (8%)
      uncircumcised patients. Interstitial irradiation for penile carcinoma provided
      effective local control rates, especially for T1-T2 patients (91%). Local
      failures could be treated successfully with surgery. Complications could be
      treated conservatively in most patients. Local control with penile conservation
      was achieved in 67% of all patients and 75% of patients with T1-T2 disease.

PMID- 1399732
TI  - Interstitial iridium-192 for bladder cancer (a multicentric survey: 205
      patients).
AB  - Interstitial irradiation is a technique currently used in the treatment of
      bladder cancer. We report the data on 205 patients (177 men and 28 women) treated
      in eight French centers. The patients had received the following treatment: a
      short course of pre-operative pelvic irradiation, followed by surgery consisting
      of partial cystectomy or tumor resection, and implantation of plastic tubes
      filled with inactive lead wires, which were replaced by iridium 192 wires. The
      tumor characteristics were: transitional cell carcinoma, 88.8%; mean size of the
      tumor, 29 mm; pathological stages: pTis, 1; pT1, 98; pT2, 66; pT3a, 26; pT3b, 9;
      pT4, 1; unknown, 4 respectively; surgical lymph node status: N+, 3; N-, 118; no
      node dissection, 84. The mean follow-up was 51 months. Intravesical failures were
      seen in 35 patients (17.0%), 25 (71.4%) of them without metastases or regional
      recurrences. Twenty-one patients (10.2%) presented distant metastases, 2/3 of
      them suffered no bladder relapse. The 5-year survival, calculated according to
      the Kaplan-Meier method (all causes of death taken together) was 77.4% for the
      T1, 62.9% for the T2, and 46.8% for the T3. Fifty-three patients had immediate
      side-effects and three died from surgical complications. Twenty-nine patients had
      delayed bladder side-effects (haematuria, fistula, chronic cystitis). Six
      patients presented an ureteral stenosis. Of the disease-free survivors, 96.1%
      retained the bladder function. Three factors were significantly predictive of
      delayed side-effects: partial cystectomy, pre-operative radiotherapy total dose,
      and linear activity of the wires (p < 0.01). Comparing our results to different
      authors' series interstitial irradiation is likely to provide a high local and
      general control of the disease and good quality of life in patients with selected
      tumors.

PMID- 1399734
TI  - Conformal static field radiation therapy treatment of early prostate cancer
      versus non-conformal techniques: a reduction in acute morbidity.
AB  - Patients with early prostate cancer have been definitively treated using our
      previously described technique of CT-based 3D treatment planning and beam's eye
      view techniques with patients immobilized in alpha cradle casts. An average of
      14% bladder (range 6-31%) and 14% rectal (range 7-25%) volume receiving a given
      dose was eliminated using four conformally blocked fields, with a 1.5 cm margin
      around the prostate contour, when compared to stage matched controls. Treatment
      related acute morbidity was compared for 26 patients treated by the conformal
      techniques (CG) since April 1989 and 20 consecutive patients treated immediately
      prior to the conformal techniques with prostate only fields from May 1985-March
      1989 (NCG). Acute urinary symptoms (frequency, dysuria, hematuria) or acute
      rectal symptoms (diarrhea, tenesmus, blood) occurred in 77% (20/26) of the CG
      versus 80% (16/20) of the NCG patients. Only 31% (8/26) of the CG versus 60%
      (12/20) of the NCG patients (p < .05) experienced symptoms to a degree which
      prompted physician intervention (medication and/or interruption of treatment).
      Two of 26 CG patients (8%) required medication for both bladder and rectal
      symptoms compared to 5/20 (25%) NCG patients (p = .09). Symptoms persisted for an
      average of 2.5 weeks versus 3.5 weeks in the CG and NCG groups, respectively.
      Persistent symptoms at or beyond the 1 month follow-up were present in 3/26 (11%)
      CG patients (average duration 1.5 months) and were present in 4/20 (20%) of the
      NCG patients (average duration 2.5 months). Thus, although the percentage of
      patients who experience acute irritation of the bladder and/or rectum is similar
      in the two groups, it appears that the percentage requiring medication and/or
      interruption of treatment is significantly less when 3D treatment planning, rigid
      immobilization, and conformal blocks are used. The amount of bladder and rectal
      tissue that is eliminated by our conformal technique is important as shown
      clinically by the lesser severity and shorter duration of acute symptomatology.

PMID- 1399735
TI  - Phase I/II study of external radio frequency phased array hyperthermia and
      external beam radiotherapy in the treatment of prostate cancer: technique and
      results of intraprostatic temperature measurements.
AB  - As part of an ongoing Phase I/II study at Duke University Medical Center
      investigating the toxicity and efficacy of external beam radiotherapy plus
      hyperthermia for deep-seated, locally advanced or recurrent solid tumors, 12
      patients with prostate malignancies (adenocarcinoma--11, leiomyosarcoma--1) were
      treated with radiotherapy plus hyperthermia. Hyperthermia was given after
      radiotherapy using a Radio Frequency Phase/Amplitude Control Sigma 60 annular
      phased array device. All patients had simultaneous temperature measurements made
      in the rectal lumen and within the prostate during at least one hyperthermia
      session. Intraprostate thermometers were placed via a unique method described
      herein using both computerized tomography scan and a rigid sigmoidoscope for
      guidance. We were able to achieve the desired tumor temperature of > or = 42.5
      degrees C in only 1/28 (3.5%) of hyperthermia treatments. Subjective symptoms of
      pain and/or pressure limited power deposition in 79% of hyperthermia treatments.
      Higher temperatures were achieved in the distal rectum than in the prostate in
      all treatments, although the differences were not statistically significant. This
      temperature differential could not be compensated by using phase and amplitude
      steering. Rectal temperatures adjacent to the prostate were predictive of
      prostate temperatures. We conclude that using this regional heating technique we
      were unable to demonstrate an ability to get an advantageous temperature
      differential between the prostate and normal tissue. This technique is not useful
      as an adjuvant to radiation therapy for prostate cancer. The usefulness of other
      regional heating techniques and devices should be explored.

PMID- 1399736
TI  - Accelerated fractionation radiotherapy for laryngeal cancer, acute, and late
      toxicity.
AB  - The acute toxicity of an accelerated radiotherapy scheme was compared with a
      conventional schedule. Eighteen patients with squamous cell carcinoma of the
      larynx were treated with accelerated fractionation radiotherapy. An average
      reduction of overall treatment time of 11 days was accomplished by giving 2
      fractions a day during the last part of the treatment. Total dose and fraction
      dose were left unchanged. Acute reactions of skin and mucosa in these patients
      were compared with those in 40 patients treated with a conventional fractionation
      scheme, that is, 2 Gy per fraction, 5 fractions per week, to a total dose of 64
      70 Gy. Acute reactions were maximal between 5 and 7 weeks after the start of
      treatment. Complete healing occurred within 3 months in all patients. Mucosal
      reactions and, as a consequence, dysphagia were clearly increased in those
      patients treated with accelerated fractionation. For confluent mucositis an ED50
      of 66 Gy was calculated compared to 69 Gy for conventional fractionation. To a
      lesser degree, skin toxicity was also enhanced in the patients treated with the
      accelerated schedule. Severe edema of the laryngeal mucosa occurred only in
      patients treated to a total dose of 68 or 70 Gy and was somewhat more frequent
      with accelerated fractionation (4/10) than with conventional fractionation
      (4/24). One patient in the accelerated fractionation group underwent laryngectomy
      for persistent edema and laryngeal necrosis. No severe late skin reactions were
      observed. It can be concluded that the fractionation schedule tested in this
      study is feasible. Further shortening of overall treatment time without reduction
      of total dose will likely lead to unacceptable acute and, possibly, also late
      toxicity.

PMID- 1399737
TI  - Radiation tolerance and fractionation sensitivity of the developing rat cervical
      spinal cord.
AB  - To investigate the influence of age at irradiation on single dose radiation
      tolerance and fractionation sensitivity, the cervical spinal cord of rats was
      irradiated at the age of 1 week and at 15-18 weeks (adult). While the main
      histological lesions seem to be comparable after irradiation at the two ages,
      differences were found in single dose tolerance, latency to paresis due to white
      matter lesions, and fractionation sensitivity. The 50% effect dose (ED50) for
      single dose irradiation at one week was 19.5 Gy, which is only 10%, but
      significantly (p < 0.05), lower than the ED50 of about 21.5 Gy at 3 weeks and
      above. The latency to paresis was clearly influenced by the age at irradiation.
      The latency in the rats irradiated at 1 week was about 2 weeks, while for adult
      rats a latency of about 8 months was observed. The fractionation sensitivity for
      irradiation at 1 week was lower than the fractionation sensitivity of the adult
      rats; the alpha/beta value at 1 week was estimated to be 4.5 Gy, while for the
      adult rats an alpha/beta value of 1.8 Gy was found. As a consequence, the
      observed small difference in tolerance to single doses between 1 week-old and
      adult rats is further enhanced after fractionated irradiation. During prolonged
      irradiation treatments this decreased tolerance may be compensated by a higher
      proliferation rate in the immature central nervous system. The results of the
      present experiments indicate that, for a single tissue and endpoint, paresis due
      to white matter lesions in the rat cervical spinal cord, the latency to
      expression of damage and the fractionation sensitivity clearly change with age at
      irradiation.

PMID- 1399738
TI  - The hybrid spheroid clonogenic assay for the intrinsic radio- and chemo
      sensitivities of human tumors.
AB  - The Hybrid Spheroid assay is based on packaging tumor cells into agglomerates of
      non-proliferating, but metabolically active, HeLa cells. These agglomerates
      provide an in vivo-like environment for entrapped test cells. Clonogenicity is
      determined by varying the number of test cells per hybrid spheroid so that some,
      but not all, spheroids give rise to macrocolonies. From the fraction of noncolony
      forming spheroids and the Poisson distribution, the average number of clonogens
      per spheroid can be calculated. The clonogenicity and radiation survival curves
      of cells derived from human tumors (of the maxilla, tongue, larynx, mouth floor,
      lung, breast, ovary, and colon) were so determined. Plating efficiency was
      increased in these normally poorly plating tumor cells, thus enabling survival
      measurements which are not practical using conventional methods. The Hybrid
      Spheroid assay has also been applied to determine the chemosensitivity of colon
      cancer cells.

PMID- 1399740
TI  - Cellular glutathione (GSH) and glutathione S-transferase (GST) activity in human
      ovarian tumor biopsies following exposure to alkylating agents.
AB  - In vitro studies have suggested that elevated levels of the thiol glutathione
      (GSH) may be associated with acquired alkylating agent resistance, but there is
      currently little data on the relationship between elevated GSH and glutathione S
      transferase levels and clinical alkylating agent resistance. In this study, GSH
      and glutathione S-transferase levels have been determined in 23 human ovarian
      tumor samples obtained prior to the onset of combination chemotherapy, and in 23
      samples obtained after the development of acquired chemoresistance. GSH levels
      were 10-fold greater in human ovarian tumor cells obtained after alkylating agent
      resistance developed, than in biopsy samples obtained prior to treatment. No
      significant changes in the expression of total glutathione S-transferases were
      seen in relation to prior drug exposure.

PMID- 1399739
TI  - Heterogeneity of 5-fluorouracil radiosensitivity modulation in cultured mammalian
      cell lines.
AB  - There is ample evidence that 5-fluorouracil (5-FU) improves both local control
      and survival of a variety of gastrointestinal tumors when added to radiotherapy.
      However, the modulation of radiosensitivity by 5-FU is incompletely understood
      and some reports are apparently contradictory. Therefore, we have reevaluated the
      modulation of radiosensitivity by 5-FU in a variety of mammalian cells. HT-29 and
      WiDr (human colon adenocarcinoma), DU-145 (human prostate adenocarcinoma), V-79
      (Chinese hamster lung fibroblast), and HeLa cell lines were maintained in
      exponential growth as monolayer cultures. Cell survival following treatment with
      drug and/or radiation was determined by colony formation assay. Radiation was
      delivered either alone; midway through a 1 hr exposure to 7-25 micrograms/ml 5-FU
      (pulse); or following initiation of 0.1-1.5 micrograms/ml 5-FU present throughout
      the entire incubation for assay of colony forming ability (continuous exposure).
      These 5-FU levels were selected to approximate those achieved in vivo in humans.
      The results indicate that mammalian cell lines may vary substantially insofar as
      modulation of their radiosensitivity by 5-FU is concerned. Radiosensitization,
      defined by reduction in D0, was observed for continuous exposure only in V-79,
      WiDr, and HT-29 cell lines, was observed for both pulse exposure and continuous
      exposure in DU-145, and was not present in HeLa cells. Radioenhancement, defined
      by reduction in n, was observed in V-79, WiDr, and HT-29 but not in the other
      cell lines. This effect, characterized by reduction in the shoulder portion of
      the curve, is naturally accompanied by a decrease of Dq. This indicates that
      mammalian cell lines may have different responses to radiosensitivity modulation
      by 5-FU. Though the cell lines may exhibit radiosensitivity by either alterations
      in the slope or shoulder of the cell survival curve, the mechanisms responsible
      for both the heterogeneity as well as the radiosensitization itself are
      completely unknown at this time. Insight into the mechanisms for both the
      heterogeneity and the radiosensitization will be important areas for further
      investigation.

PMID- 1399741
TI  - Radiosensitivity of mouse skin epithelial cell line established in serum-free
      culture: an alternative to animal use.
AB  - A cultured line of murine skin epithelial cells was established to investigate
      the potential use of cultured cells as an alternative to animal use in radiation
      research. C3Hf/Sed newborn mouse skin cells have been successfully cultured in
      serum- and Ca(2+)-free medium with no terminal differentiation to keratinized
      cells. Presently, more than 25 passages have passed with no loss of stem cell
      capability. The radiosensitivity and repair of sublethal and potentially lethal
      radiation damages were investigated in this epithelial cell line. The population
      cell doubling time was 25 +/- 2.9 hr at 37 degrees C. The clonal growth of
      epithelial cells after irradiation was performed in the serum-free medium in the
      presence of lethally irradiated skin fibroblasts. Single dose survival curves of
      exponentially growing epithelial cells were investigated from the seventh to the
      twenty-third passages, and no significant changes in radiosensitivity and
      doubling time were found. The confluent epithelial cells also showed an identical
      sensitivity to radiation. The alpha/beta ratios of survival curves fitted by the
      linear quadratic model were 6.1 +/- 1.0 and 5.9 +/- 1.3 Gy for cells in
      exponential and confluent phases, respectively. The survival curve of epithelial
      cells left in confluence for 8 hr after irradiation showed a smaller beta value
      than that of cells plated immediately after irradiation with a resultant
      alpha/beta ratio of 9.5 +/- 3.8 Gy. This alpha/beta ratio was identical to those
      found in many animal experiments, suggesting a potential use of this cell line as
      an alternative to animal use. The magnitude of repair of sublethal damage
      following 6 Gy was greater than that following 3.9 Gy. Survival curves were also
      obtained following twice-a-day irradiations with no sign of rapid repopulation.
      These results are discussed by comparing with published in vivo and in vitro
      data.

PMID- 1399742
TI  - Changes in heat and radiation sensitivity during long duration, moderate
      hyperthermia in HeLa S3 cells.
AB  - Step-up heating and thermal radiosensitization were studied at 41.5 degrees C in
      HeLa S3 cells under conditions where chronic thermotolerance was not expressed.
      In spite of this lack of thermotolerance expression, it was possible that
      thermotolerance to higher temperature treatment had developed. Accordingly, cells
      were incubated for various times at 41.5 degrees C, then immediately shifted up
      to 45 degrees C, whereupon heating continued for up to 75 min. Thermotolerance to
      45 degrees C heating was observed after 8 hr incubation at 41.5 degrees C and
      decayed by 32 hr of continuous incubation at 41.5 degrees C. When the time of 45
      degrees C treatment was extended to 150 min, the biphasic survival response
      indicated that chronic thermotolerance was expressed at 45 degrees C, even though
      it was not expressed during the 41.5 degrees C treatment. Thus, chronic
      thermotolerance can develop under conditions (e.g., at 41.5 degrees C) where it
      is not expressed, yet be expressed under other conditions (e.g., during 45
      degrees C exposure). When cultures were x-irradiated after various periods of
      41.5 degrees C treatment, maximum thermal radiosensitization was observed after 4
      hr of incubation at 41.5 degrees C, for which no cell killing was observed due to
      heat alone. The radiosensitization observed decreased the Do and Dq values from
      about 1.3 Gy to 0.7 Gy and from about 2.0 Gy to 1.0 Gy, respectively. As the
      duration of the 41.5 degrees C pre-treatment was extended up to 32 hr, no
      additional thermal-radiosensitization was observed; all killing due to the heat
      exposure at 41.5 degrees C was additive to the radiation killing after the
      initial induction of thermal radiosensitization. These results demonstrate
      differences in the thermal and radiation responses of HeLa cells when compared to
      earlier studies using CHO cells and may be more relevant to the clinical setting.

PMID- 1399743
TI  - Ultrasonically guided transperineal seed implantation of the prostate:
      modification of the technique and qualitative assessment of implants.
AB  - During the period 1988-1991, 23 patients with prostatic carcinoma were treated by
      transperineal iodine seed implantation guided by transrectal ultrasound. We
      introduce a refinement of the implantation technique using a rigid column of
      seeds and spacers. The uniformity parameter based on the peak width of the
      natural volume-dose histogram demonstrated quantitatively that this refinement
      resulted in a more accurate seed arrangement.

PMID- 1399744
TI  - Quality assurance for intraoperative electron radiotherapy clinical trials:
      ionization chamber and mailable thermoluminescent dosimeter results.
AB  - Ionization chamber and thermoluminescent dosimeter measurements were made to
      verify the dosimetry data provided to the Radiation Therapy Chart Review office
      of interinstitutional electron intraoperative radiotherapy clinical trials. The
      ionization measurements included intraoperative radiotherapy applicator output
      and depth dose measurements made at the stated 80% and 50% depths at 14 different
      radiotherapy facilities. Mailable thermoluminescent dosimeter measurements,
      including output and depth dose measurements were made at 16 institutions. The
      mailable thermoluminescent dosimeter results show similar inter-institutional
      agreement, both for output and depth dose comparison, with the corresponding ion
      chamber results for intraoperative radiotherapy applicators. These results are
      compared to similar measurements made for conventional electron applicators.

PMID- 1399745
TI  - Gene therapy targeted by ionizing radiation.
AB  - Gene therapy used for the treatment of neoplastic diseases is not well localized.
      Ionizing radiation can be used to activate the transcription of exogenous genes
      that encode cytotoxic proteins. This may be accomplished through the use of
      radiation responsive elements distal to the transcription start site of such
      genes. We discuss this concept and describe a technique which can be used to
      amplify the signal initiated by localized radiation therapy. These techniques may
      be used to target gene therapy during the treatment of human neoplasms.

PMID- 1399746
TI  - The earlier the better or unnecessary therapy?

PMID- 1399747
TI  - Post treatment biopsies of the prostate: a stalking horse for improving local
      control.

PMID- 1399748
TI  - Response to Dr. Oleson.

PMID- 1399749
TI  - Social interaction, cardiovascular activation and the Type A behavior pattern.
AB  - The purpose of the study was to explore the relationship between social
      interaction and cardiovascular activity during a conflict-inducing communication
      task in Type A and B subjects. One of the subjects, the leader, was instructed to
      lead the other subject, the follower, through defined routes on a city map merely
      by help of instructions. The subjects were facing each other on each side of a
      screen which allowed eye contact but shielded the maps from view. 40 male
      students (mean age 24 years) exhibiting Type A or Type B behavior according to
      the Videotaped Structured Interview participated in the study. The results
      demonstrated large cardiovascular increases during task performance, particularly
      for leaders, in systolic blood pressure and heart rate. There were no main
      effects of Type A vs. Type B, but dyads composed of two Type As showed larger
      increase in diastolic blood pressure during the conflict phase of the task
      compared to dyads composed of Type Bs.

PMID- 1399750
TI  - Effect of task difficulty and interstimulus interval on blink parameters.
AB  - The effects of task difficulty and interstimulus interval (ISI) on blink rate,
      blink latency and blink duration, were studied in a modified Sternberg memory
      task in which either two or six characters were to be memorized. Stimuli were
      presented in ISI blocks at either 5.3 or 9.3 s (SOAs of 6 or 10 s). While blink
      rate and blink duration declined prior to each stimulus, the difficulty of the
      expected task (the length of the memory set) did not affect the rate of decline
      or the final prestimulus level. Concerning ISI, blink rate declined more rapidly
      during shorter ISIs but the final prestimulus level, as was the case with task
      difficulty, was unaffected by the ISI duration. Presentation of the 6-character
      memory set produced a marked immediate inhibition of blinking. The data suggest
      that the encoding of visual stimuli is more akin to processes invoked in
      preparation for input than to ensuing processing stages since both encoding as
      well as preparation are accompanied by inhibition of blinking.

PMID- 1399751
TI  - Directed coherence as a measure of interhemispheric correlation of EEG.
AB  - Based on a bidirectional model and the temporal relation of the signals, directed
      coherence is defined to describe the EEG correlation according to the direction
      of information transmission in the frequency domain. The interhemispheric
      directed coherences of EEG pairs in the prefrontal, frontal, central, parietal
      and occipital cortices were investigated. Statistically, significantly greater
      right-left directed coherences were found in the parietal and occipital regions
      than that of the left-right direction for alpha activity. The results indicate
      different information processing for different frequency bands between the left
      and right hemispheres, and this can not be derived from the examination of
      original coherence. This may suggest that the measure of directed coherence can
      provide more information than that of original coherence.

PMID- 1399752
TI  - Electrodermal differentiation of deception: potentially confounding and
      influencing factors.
AB  - The demonstration of deception as a psychological process requires a comparison
      of physiological responding to questions answered honestly or deceptively, under
      conditions which differ only with respect to deception. Such electrodermal (skin
      conductance response (SCR) differentiation was recently reported in the
      Differentiation-of-Deception Paradigm. The present study had two empirical goals:
      (a) to assess the possible confounding role of retrieval-difficulty and novelty
      in producing the differentiation effect; (b) to ascertain any influencing effects
      of a memorial ('cumulative' mental load) and two motivational (Monetary-Incentive
      and Ego-Involvement) factors on the electrodermal differentiation phenomenon and
      on overall responding. In addition to the basic Deceptive vs. Honest manipulation
      of the Differentiation-of-Deception Paradigm, the present study varied, within 60
      subjects, Question Type (easily retrieved Autobiographical vs. more difficult-to
      retrieve Biographical). The two two-level motivational factors were varied
      between subjects. Finally, to assess the confounding issue, voice latency (VL),
      known to be sensitive to retrieval-difficulty, was measured in addition to SCR.
      SCRs to deceptive answers exceeded those to the honestly-answered questions,
      demonstrating the differentiation phenomenon. Results showed that although VL and
      SCR was significantly greater to Biographical than to Autobiographical questions,
      the differentiation effect emerged only in the SCR and not in VL, which suggests
      that memorial difficulty does not confound the electrodermal differentiation
      effect.

PMID- 1399753
TI  - Anxiety, emotion and cerebral blood flow.
AB  - Regional cerebral blood flow was measured by the xenon inhalation technique using
      a DSPECT system, during neutral and emotional auditory stimulations. Subjects
      were 10 high and 10 low trait anxiety, right-handed females. State anxiety was
      retrospectively assessed. Results indicated a lower rCBF in the high trait or
      state anxiety subjects who presented also a global rCBF asymmetry in the right >
      left direction. Additionally, the emotional content of the stimuli interacted
      significantly with the side of the brain in the thalamic area.

PMID- 1399754
TI  - Theta rhythmicities following expected visual and auditory targets.
AB  - Evoked (EPs) as well as event-related potentials (ERPs) were recorded from two
      groups of 10 healthy, voluntary subjects in auditory and visual modalities. For
      ERP recordings 'the omitted stimulus paradigm' was employed, in which the
      subjects were expected to mark mentally the onset time (time prediction task) of
      the omitted stimulus (target). The standard auditory (AEP) and visual (VEP)
      evoked potentials and auditory and visual ERPs to the preceding stimuli of the
      omitted ones were analyzed in time and frequency domains. In the time domain the
      time prediction task induced increases of the amplitudes of waves existing in
      standard EPs; however, an additional wave or component could not be detected.
      Analysis of amplitude frequency characteristics (AFCs) revealed, however,
      selective, significant increases of the theta (3-6 Hz) frequency components of
      the responses concerned. These theta increases were especially evident in the
      frontal and parietal recording sites. Our findings suggest an association between
      the theta frequency components of transient evoked responses, the association
      areas of the brain and cognitive performance. The neurophysiological basis of
      scalp recorded ERPs are discussed in relation to the findings of animal studies
      with EEG and single unit recordings from cortical and subcortical structures.

PMID- 1399755
TI  - P300-response: possible psychophysiological correlates in delta and theta
      frequency channels. A review.
AB  - The present paper combines a review of event-related potentials (ERPs) with
      empirical data concerning the question: what are the differences between auditory
      evoked potentials (EPs) and two types of ERPs with respect to their frequency
      components? In this study auditory EPs were elicited by 1500 Hz tones. The first
      type of ERPs was responses to 3rd attended tones in an omitted stimulus paradigm
      where every 4th stimulus was omitted. The second type of ERPs was responses to
      rare 1600 Hz tones in an oddball paradigm. The amplitudes of delta and theta
      components of EPs and ERPs showed significant differences: in responses to 3rd
      attended tones there was a significant increase in the theta frequency band
      (frontal and parietal locations; 0-250 ms). In the delta frequency band there was
      no significant change. In contrast a diffuse delta increase occurred in oddball
      responses and an additional prolongation of theta oscillations was observed (late
      theta response: 250-500 ms). These results are discussed in the context of ERPs
      as induced rhythmicities. The intracranial sources of ERPs, their psychological
      correlates and the role of theta rhythms in the cortico-hippocampal interaction
      are reviewed. From these results and from the literature a working hypothesis is
      derived assuming that delta responses are mainly involved in signal matching,
      decision making and surprise, whereas theta responses are more related to focused
      attention and signal detection.

PMID- 1399756
TI  - How to select epochs of cognitive event-related potentials for brain mapping?
AB  - Event-related potentials were recorded in healthy volunteers while they were
      performing cognitive tasks. The new parameter developed for evaluation of how
      ERPs from different electrodes are not like each other allowed to study the
      mental chronometry as well as the localization of specific cortical areas.
      Occipital lobes were most active in passive visual word perception, the left
      anterior frontal lobe was activated in semantic association. The developed
      approach allows the combination of imaging and chronometric studies.

PMID- 1399757
TI  - Contingent negative variation as an indicator of sexual object preference:
      revisited.
AB  - This study attempted to replicate the finding of Costell et al. (1972) that
      contingent negative variation (CNV) in anticipation of opposite sex nudes is of
      greater amplitude than CNV in anticipation of same sex nudes. In order to control
      for variation in level of attention, which may have accounted for the result of
      Costell et al., a 'match/mismatch' CNV paradigm was used in which S2 was either
      identical to S1 or differed from it. Subjects (n = 6 males) were required to
      indicate a same/different judgement by button pressing at S2 offset. CNV in
      anticipation of opposite sex nudes was of significantly greater amplitude than
      CNV in anticipation of same sex nudes, confirming the finding of Costell et al.
      This offers encouragement for the application of CNV to the assessment of sexual
      object preference in sex offenders.

PMID- 1399758
TI  - Spicy meal disturbs sleep: an effect of thermoregulation?
AB  - Tabasco sauce and mustard taken with the evening meal markedly disturbed sleep of
      six, young, healthy male subjects; reducing slow wave and stage 2 sleep,
      increasing total time awake and tending to increase sleep onset latency. Whilst
      post meal effects on temperature and oxygen consumption were not significantly
      different from control meals the spicy food condition elevated body temperature
      during the first sleep cycle. The possibility that the spice principle capsaicin
      affects sleep via changes in body temperature is discussed.

PMID- 1399759
TI  - A physiologic concept of exercise-induced pulmonary hemorrhage in horses.

PMID- 1399760
TI  - Comments on cosmetic surgery.

PMID- 1399761
TI  - Comments on cosmetic surgery.

PMID- 1399762
TI  - Comments on cosmetic surgery.

PMID- 1399763
TI  - Comments on cosmetic surgery.

PMID- 1399764
TI  - Comments on cosmetic surgery.

PMID- 1399765
TI  - FDA tightens screws on extra-label drug use, liberalizes policy on use of human
      drugs in animals.

PMID- 1399766
TI  - Demographic and employment shifts of US veterinarians, 1980 to 1990.

PMID- 1399767
TI  - Raising orphaned sea otter pups.

PMID- 1399768
TI  - The best of times.

PMID- 1399769
TI  - Blind percutaneous placement of a gastrostomy tube for nutritional support in
      dogs and cats.

PMID- 1399770
TI  - Veterinarians as expert witnesses--some recent decisions.

PMID- 1399771
TI  - Effects of countercurrent scalding and postscald spray on the bacteriologic
      profile of raw chicken carcasses.
AB  - In June and September 1988, the USDA Food Safety and Inspection Service sampled
      raw chicken carcasses at a federally inspected slaughter establishment in Puerto
      Rico to determine the effects of changing the scalding equipment on bacterial
      contents of raw poultry products. The scalding equipment was changed to a
      countercurrent configuration, with a postscald hot-water rinse cabinet that
      sprayed carcasses as they exited the scalder. Analysis of 250 carcass-rinse
      samples collected at preevisceration, prechill, and postchill sites over 7 days
      indicated that carcasses had mean aerobe plate counts of log(10)3.73 before
      evisceration, 3.18 before chilling, and 2.87 after chilling; Enterobacteriaceae
      counts of log(10)2.70 before evisceration, 2.25 before chilling, and 1.56 after
      chilling; and Escherichia coli counts of log(10)2.09 before evisceration, 1.61
      before chilling, and 0.89 after chilling. Salmonellae were found on 24% of the
      carcasses before evisceration, on 28% before chilling, and on 49% after chilling.
      Although bacterial count reductions were significant at all 3 sites, the
      proportion of carcasses contaminated with salmonellae in this study was higher at
      the postchill than prechill site (49 vs 28%). This no doubt was caused by cross
      contamination in the chiller. These percentages indicated that although simple
      scalder changes contributed substantially to the improvement of the bacterial
      quality of chicken carcasses, additional interventions in the chilling process
      (such as chlorination of chill water) are important to control cross
      contamination and to preserve the positive effects obtained by the scalder
      changes.

PMID- 1399772
TI  - Induced transplacental transmission of Neospora caninum in cattle.
AB  - Three Jersey cows were inoculated SC and IM with 26 million Neospora caninum
      tachyzoites at 129 (cow 1), 126 (cow 2), and 81 (cow 3) days after mating. Cows
      remained clinically normal for at least 1 month after inoculation of N caninum.
      Cow 1 was euthanatized 32 days after inoculation because of gangrenous mastitis.
      Cow 1 had a live fetus with no gross lesions; however, microscopic lesions were
      seen in the fetus and consisted of severe nonsuppurative necrotizing encephalitis
      of the cerebral white matter. Neospora caninum was identified in lesions by
      staining with anti-N caninum serum in an immunohistochemical test, by bioassays
      in mice, and by inoculation of bovine monocyte cultures with fetal tissue
      homogenate. Neither N caninum nor lesions were associated with infection with the
      protozoon identified in tissues of cow 1. Cows 2 and 3 aborted small autolysed
      fetuses 101 and 74 days, respectively, after inoculation with N caninum; the
      fetuses and attached placenta were unsuitable for laboratory investigations. Cows
      2 and 3 remained clinically normal 4 months after abortion. Results of this study
      indicated that N caninum can be transmitted transplacentally in cattle.

PMID- 1399773
TI  - Characterizing biological variability in livestock blood cholinesterase activity
      for biomonitoring organophosphate nerve agent exposure.
AB  - A biomonitoring protocol, using blood cholinesterase (ChE) activity in livestock
      as a monitor of potential organophosphate nerve agent exposure during the planned
      destruction of US unitary chemical warfare agent stockpiles, is described. The
      experimental design included analysis of blood ChE activity in individual healthy
      sheep, horses, and dairy and beef cattle during a 10- to 12-month period.
      Castrated and sexually intact males, pregnant and lactating females, and adult
      and immature animals were examined through at least one reproductive cycle. The
      same animals were used throughout the period of observation and were not exposed
      to ChE-inhibiting organophosphate or carbamate compounds. A framework for an
      effective biomonitoring protocol within a monitoring area includes establishing
      individual baseline blood ChE activity for a sentinel group of 6 animals on the
      bases of blood samples collected over a 6-month period, monthly collection of
      blood samples for ChE-activity determination during monitoring, and selection of
      adult animals as sentinels. Exposure to ChE-inhibiting compounds would be
      suspected when all blood ChE activity of all animals within the sentinel group
      are decreased greater than 20% from their own baseline value. Sentinel species
      selection is primarily a logistical and operational concern; however, sheep
      appear to be the species of choice because within-individual baseline ChE
      activity and among age and gender group ChE activity in sheep had the least
      variability, compared with data from other species. This protocol provides an
      effective and efficient means for detecting abnormal depressions in blood ChE
      activity in livestock and can serve as a valuable indicator of the extent of
      actual plume movement and/or deposition in the event of organophosphate nerve
      agent release.

PMID- 1399774
TI  - Ivermectin treatment of naturally acquired and experimentally induced
      Strongyloides stercoralis infections in dogs.
AB  - Treatment of Strongyloides stercoralis infection was investigated in 2 dogs with
      naturally acquired, chronic-active infections, and in 3 dogs with corticosteroid
      enhanced, experimentally induced hyperinfections. A single oral dose of
      ivermectin was given to naturally infected (200 micrograms/kg of body weight) and
      experimentally infected (800 micrograms/kg) dogs. Five dogs with experimental
      hyperinfections served as controls. Dogs with naturally acquired infections
      ceased to shed first-stage larvae in the feces 1 week after treatment, but 1 dog
      had recrudescence and required a second dose. Ivermectin was 100% effective in
      removing adult S stercoralis from the intestinal tract of the experimentally
      infected dogs, but it was not effective in removing third-stage larvae from
      parenteral sites. Ivermectin-treated dogs had few intestinal parasites of any
      stage, whereas at necropsy, 4 of 5 experimentally infected dogs not treated had
      massive infections (greater than 100,000 adults, greater than 92,000 larvae) in
      the intestinal tract, and 3 of 5 had larvae (greater than 2,500) in parenteral
      sites.

PMID- 1399775
TI  - Episodic weakness associated with exertional lactic acidosis and myopathy in Old
      English sheepdog littermates.
AB  - Two Old English Sheepdog littermates were evaluated for weakness that developed
      during periods of minimally intense exercise. Lactic acidosis accompanied by
      increased muscle enzyme activity, an increased lactate/pyruvate ratio, and
      increased venous PO2 supported the possibility of defective mitochondrial oxygen
      use. Electromyographic abnormalities included increased insertional activity and
      complex repetitive discharges. Muscle alterations included scattered myofiber
      necrosis, abundant endomysial connective tissue, excessive glycogen accumulation,
      and greater than normal numbers and vacuolation of mitochondria. A distinctive
      pattern of subsarcolemmal mitochondrial aggregates, referred to as "ragged red
      fibers" in human mitochondrial myopathies, was observed in muscle biopsy samples
      from 1 dog. Several features of the disease in these dogs, including onset of
      weakness during early life, simultaneous disease in littermates, subtle
      nonprogressive weakness of at least 3 years' duration, and partial reversibility
      of lactic acidosis following rest were suggestive of an inborn error of
      metabolism, consistent with mitochondrial myopathy.

PMID- 1399776
TI  - Paraneoplastic leukocytosis associated with a rectal adenomatous polyp in a dog.
AB  - A dog with a rectal adenomatous polyp had extreme neutrophilic leukocytosis,
      monocytosis, and eosinophilia consistent with a paraneoplastic syndrome.
      Resolution of the leukogram abnormalities after tumor excision supported this
      belief. Except for a lack of circulating myeloblasts, the dog had leukogram
      findings consistent with a neutrophilic leukemoid reaction.

PMID- 1399777
TI  - Belt loop gastropexy in the management of gastroesophageal intussusception in a
      pup.
AB  - Gastroesophageal intussusception and megaesophagus were diagnosed in a 5-week-old
      German Shepherd Dog. Exploratory surgery was performed, and belt loop gastropexy
      was used to maintain proper gastric position after manual reduction of the
      intussusception. The pup survived surgery and was clinically normal when it was 6
      months old. Follow-up contrast radiography revealed resolution of the
      megaesophagus and apparent permanent gastropexy. Previous reports have indicated
      extremely high mortality for gastroesophageal intussusception, and resolution of
      megaesophagus in the dog is unusual.

PMID- 1399778
TI  - Ultrasonographic characteristics of splenic and hepatic lymphosarcoma in three
      horses.
AB  - Splenic and hepatic ultrasonography were beneficial for diagnosis of
      lymphosarcoma in 3 horses with anorexia, weight loss, and lethargy.
      Ultrasonographic abnormalities of the spleen included a large, complex,
      hypoechoic mass in 1 horse, multiple well-marginated, hypoechoic nodules in 1
      horse, and diffuse hyperechogenicity in another horse. Ultrasonographic
      abnormalities of the liver included a spherical, hypoechoic nodule in 1 horse and
      diffuse hyperechogenicity in another. Histologic examination of ultrasound-guided
      biopsy specimens or aspirates revealed lymphosarcoma. Necropsy findings confirmed
      diagnosis of lymphosarcoma in all horses. Necropsy findings of the liver and
      spleen correlated well with antemortem ultrasonographic images.

PMID- 1399779
TI  - Tubular duplication of the cervical portion of the esophagus in a foal.
AB  - Tubular duplication of the cervical portion of the esophagus was diagnosed in a
      10-day-old female Quarter Horse. The foal was examined because of the development
      of a 12- to 15-cm diameter mass at the caudal aspect of the mandible after
      suckling. The foal was dyspneic when in lateral recumbency. Radiography and
      ultrasonography revealed a fluid- and gas-filled mass. Endoscopy revealed a
      normal-appearing upper airway and esophagus. Complete surgical resection of the
      mass was successful. The mass had a 3-mm diameter communication with the
      esophageal lumen at the pharyngoesophageal oriface. Histologic examination
      revealed stratified squamous epithelium lining the cyst-like cavity. The wall of
      the mass had circumferential and longitudinal layers of smooth muscle with few
      submucosal glands. The clinical, gross pathologic, and histopathologic findings
      were consistent with tubular duplication of the cervical portion of the
      esophagus.

PMID- 1399780
TI  - Cholelith causing duodenal obstruction in a horse.
AB  - A 10-year-old Appaloosa stallion was referred for evaluation of colic. At
      admission, the heart rate, capillary refill time, respiratory rate, and rectal
      temperature were high. Fifteen liters of reflux was obtained by nasogastric
      intubation. Palpation of an abdominal mass per rectum elicited signs of pain. At
      exploratory laparotomy, a mass was palpated in the ascending portion of the
      duodenum. The small intestine ruptured at the site of obstruction during
      manipulation. The horse was euthanatized. A large cholelith was the cause of the
      duodenal obstruction. At necropsy, multiple choleliths of various sizes were
      found in the pancreatic and common bile ducts and in the stomach.

PMID- 1399781
TI  - Use of the neodymium:yttrium-aluminum-garnet laser for treatment of squamous cell
      carcinoma of the nasal planum in a cat.
AB  - A mature castrated male domestic shorthair cat was referred for treatment of an
      excoriated, ulcerated area on the nasal planum. Undifferentiated squamous cell
      carcinoma was diagnosed. Surgical resection of the nasal planum was not an
      option, so the lesion was treated 4 times with neodymium:yttrium-aluminum-garnet
      laser. Laser surgery results in uniform photovaporization of large volumes of
      tissue. Although treatment with laser does not yield tissue specimens suitable
      for histologic evaluation, it can result in a cosmetically suitable appearance
      and can extend the predicted life span. A diagnosis of undifferentiated squamous
      cell carcinoma has a guarded prognosis: however, the cat of this report survived
      more than 18 months.

PMID- 1399782
TI  - Treatment by digital amputation of subungual squamous cell carcinoma in dogs: 21
      cases (1987-1988)
AB  - Malignant digital tumors were diagnosed in 62 dogs during a 1-year period. Twenty
      one (33.9%) of the dogs had subungual squamous cell carcinoma. Each of these dogs
      had involvement of single digits. Sixteen (76.2%) of the dogs with squamous cell
      carcinoma were large-breed dogs, and 15 (71.4%) had predominantly black coats.
      Labrador Retrievers (n = 5, 23.8%) and Standard Poodles (n = 3, 14.3%) were the
      most commonly represented purebreeds. None of the dogs had evidence of metastases
      prior to treatment. All 21 tumors were treated by amputation of the involved
      digit. Histologic evidence of neoplastic bone invasion was found in 15 of the 21
      amputated digits (71.4%). Local tumor recurrences were not observed. Only 1 dog
      developed documented metastatic disease; this dog was euthanatized because of
      pulmonary metastases 5 months after surgery. At the time of this report, 9 dogs
      (42.9%) were alive with no evidence of disease (median, 26 months after surgery),
      and 11 dogs (52.4%) had died or were euthanatized (median, 20 months after
      surgery). The cause of death in 7 dogs was known to be unrelated to squamous cell
      carcinoma, and the cause of death in 4 dogs was unknown. The 1-year and 2-year
      survival rates were 76.2% and 42.9%, respectively.

PMID- 1399783
TI  - Hypoplasia of the trachea in dogs: 103 cases (1974-1990).
AB  - A multi-institutional retrospective study of 103 dogs in which hypoplasia of the
      trachea was diagnosed was conducted. Bulldogs (55%) and Boston Terriers (15%)
      were most commonly affected. Age at diagnosis ranged from 2 days to 12 years,
      with a median of 5 months. Hypoplasia of the trachea was diagnosed more
      frequently in males (66%) than females (34%). Congenital anomalies in dogs with
      hypoplasia of the trachea included elongated soft palate (n = 44), stenotic nares
      (n = 23), cardiac defects (n = 12), and megaesophagus (n = 10). Ratios between
      tracheal lumen diameter and depth of the thoracic inlet or width of the third rib
      did not correlate with dyspnea. Of 42 dogs reexamined greater than 6 months after
      diagnosis, 25 (60%) were clinically normal. The remaining 17 were dyspneic and 15
      (88%) had concurrent respiratory or cardiovascular disease that could account for
      their clinical signs. Hypoplasia of the trachea appears to be tolerated well in
      the absence of concurrent respiratory or cardiovascular disease.

PMID- 1399784
TI  - Prevalence and type of splenic diseases in cats: 455 cases (1985-1991).
AB  - Retrospective data on the type and prevalence of splenic disease in cats were
      evaluated in a large number of feline splenic tissues (n = 455) submitted as
      surgical and necropsy specimens from private veterinary hospitals in California
      during a period of approximately 5.5 years. Primary and metastatic neoplasia
      accounted for 37% of all feline splenic lesions. Mastocytoma, lymphosarcoma,
      myeloproliferative disease, and hemangiosarcoma, in that order, accounted for the
      bulk of neoplasia. Submission of accessory splenic tissue from either the omentum
      or pancreas accounted for 4% (17/455), whereas hyperplastic nodules, hematomas,
      and the combination of these changes in the spleen accounted for 4% (19/455).
      Splenitis was found in 2% (8/455) of submissions. Thromboembolism with regional
      splenic infarction accounted for 1% (4/455) of splenic lesions in cats. The
      remaining splenic lesions each accounted for less than 1% of total splenic
      submissions, and as such, were considered incidental and of questionable clinical
      importance.

PMID- 1399785
TI  - Treatment of mandibular squamous cell carcinoma in cats by use of mandibulectomy
      and radiotherapy: seven cases (1987-1989).
AB  - Seven cats with squamous cell carcinoma involving the mandible were treated by
      surgery and radiotherapy. Surgery consisted of hemimandibulectomy or combined
      rostral and hemimandibulectomy, gastrostomy tube placement, and submandibular
      lymph node excisional biopsy. Radiotherapy (orthovoltage or 60Co) commenced 2
      weeks after surgery. Histologically, the tumor invaded surgical margins in 6 of 7
      cats. Nerve infiltration was histologically identified in 2 cats. All cats had
      stage-3 disease with radiographic evidence of mandibular bone involvement. Age
      ranged between 8 and 16 years (median, 10 years). Hypercalcemia (2), feline
      immunodeficiency virus (2), and hyperthyroidism (1), were detected in cats prior
      to treatment. Survival after surgery was a median of 14 months (range = 3 to 36
      months, mean = 15 months). Six cats were euthanatized because of recurrence of
      disease at 3, 7, 9, 16, 21, and 36 months. One cat was euthanatized at 14 months
      because of an unrelated disease. Complications of tongue lagging, drooling after
      meals, mandibular drift, maxillary ulceration, and alopecia of the jaw developed
      in a few cats. Radiation at the primary site and regional lymph nodes after
      surgery of curative intent extended survival in cats with mandibular squamous
      cell carcinoma.

PMID- 1399786
TI  - Colopexy in broodmares: 44 cases (1986-1990).
AB  - Colopexies were performed in 44 broodmares requiring abdominal surgery for large
      colon volvulus or right dorsal displacement of the large colon. Colopexies were
      performed by suturing the lateral bands of the left and right ventral colon to
      the ventral abdominal wall. Forty-seven percent of the mares in which a colopexy
      was performed had previous surgery for a large colon volvulus or right dorsal
      displacement of the large colon. Postoperative complications considered directly
      associated with the colopexy procedure were intermittent abdominal pain in 7,
      reoperation in 5, subcutaneous fistulous tracts in 1, and catastrophic rupture of
      the left ventral colon in 2 horses. Thirty-six horses survived greater than 6
      months after colopexy, 34 of which had complete follow-up examinations. Twenty
      seven mares have foaled at least once subsequent to the colopexy procedure,
      totalling 40 foals. Colopexy was considered a viable technique to prevent
      recurrence of large colon displacement or volvulus in selected predisposed
      populations.

PMID- 1399787
TI  - What is your diagnosis? Multiple chip fractures of the proximal aspect of the
      fourth metacarpal bone.

PMID- 1399788
TI  - IRS rules in favor of veterinary corporations.

PMID- 1399789
TI  - Distribution of US veterinarians by gender, 1980 to 1990.

PMID- 1399790
TI  - Implications of the human/animal bond for human health and veterinary practice.

PMID- 1399791
TI  - Taming the wild computer.

PMID- 1399792
TI  - Conventional vs nonconventional medicine.

PMID- 1399793
TI  - Effects of limited food consumption on the incidence of hip dysplasia in growing
      dogs.
AB  - Forty-eight 8-week-old Labrador Retrievers were allotted to 2 groups of 24 dogs
      each; 1 group was fed ad libitum and the other group was given 25% less of the
      same feed until the dogs were 2 years old. Radiography of the hip joints was done
      when the dogs were 30, 42, 54, 78, and 104 weeks old. Subluxation was measured by
      the Norberg angle on radiographs made with the dog in the standard (extended
      limb) position. Independent of age at which the radiography was done, there was
      less subluxation of the femoral heads in the limit-fed dogs. Using the Swedish
      method of hip joint evaluation on the same radiographs, it was found that fewer
      dogs on limited food intake had signs of hip dysplasia. Radiographs done when
      dogs were 2 years old, for all the methods used (Norberg angle in standard and
      frog-limb position, the Orthopedic Foundation for Animals [OFA] score, and the
      Swedish score), revealed less hip dysplasia (less joint subluxation and less
      degenerative joint disease) in the limit-fed dogs. Using the OFA method, 7 of the
      24 limit-fed dogs and 16 of the 24 ad libitum-fed dogs were diagnosed as having
      hip dysplasia. Similarly, using the Swedish method, 5 of the 24 limit-fed dogs
      and 18 of the 24 ad libitum-fed dogs were diagnosed as having hip dysplasia. The
      food-intake-related differences were significant both for the OFA score and for
      the Swedish score.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399794
TI  - Salmonella infections in neonatal dairy calves.
AB  - To estimate herd prevalence of Salmonella spp, fecal specimens were obtained for
      culture from neonatal calves of 47 Ohio dairy herds. Of the 452 calves tested, 10
      calves from 7 farms were culture-positive. Salmonella serotypes isolated were S
      dublin, S typhimurium, S enteritidis, S agona, S mbandaka, and S montevideo. Bulk
      tank milk filters from these dairies were also submitted for culture. Salmonella
      sp was isolated from 1 of the 50 filters, and 2 calves from this herd were found
      to be shedding Salmonella sp of the same serotype.

PMID- 1399795
TI  - Effects of selenium supplementation in cattle on aquatic ecosystems in northern
      California.
AB  - The potential impact on aquatic ecosystems of supplementing the diets of beef
      cattle with selenium (Se) was studied on 4 northern California ranches. All study
      sites included an area of concentrated use by cattle that had diets supplemented
      with Se. In each case, a stream flowed through the site and provided a control
      sampling area upstream and a treated sampling area downstream. Specimens of
      water, sediment, algae, aquatic plants, aquatic invertebrates, and fish were
      analyzed fluorometrically for total Se content. Significant differences in Se
      concentration were not found between specimens from upstream control areas and
      those from downstream areas subjected to use by Se-treated cattle. Evidence was
      not found that Se supplementation in cattle at maximal permitted concentrations
      caused Se accumulation in associated aquatic ecosystems.

PMID- 1399796
TI  - Factors associated with and prevalence of high Malassezia pachydermatis numbers
      on dog skin.
AB  - The prevalence of cutaneous Malassezia spp was evaluated in a semiquantitative
      fashion at 3 sites on 98 dogs examined because of various dermatoses. Thirty
      (10.2%) of the sites and 19 (19.4%) of the dogs had Malassezia spp amounts higher
      than that found on grossly normal skin. The prevalence of higher than normal
      amounts did not correlate significantly with sample site, sex, or age. The
      factors associated with an increased prevalence of increased Malassezia spp
      counts were seborrheic dermatitis, recent antibiotic treatment, and breed.

PMID- 1399797
TI  - Acute thallium toxicosis in a dog.
AB  - A Doberman Pinscher was evaluated for acute onset of gastroenteritis,
      characterized by anorexia, hematemesis, and hematochezia. The dog had ingested
      mole bait containing thallium 2 days prior to admission. Thallium toxicosis was
      confirmed by detection of thallium in the urine, using colorimetric analysis. The
      dog responded well to administration of antibiotics, fluids administered IV, warm
      water enemas, and oral administration of activated charcoal slurries.

PMID- 1399798
TI  - Anaerobic bacterial infections causing osteomyelitis/arthritis in a dog.
AB  - A 3-year-old German Shepherd Dog was examined for lameness, signs of pain,
      swelling, a draining fistulous tract, and osteolysis after a dog bite on the left
      carpus. After failure of the lesion to respond to several antibiotics,
      Peptostreptococcus sp and Propionibacterium sp were isolated from swab specimens
      and then from surgically collected bone and soft tissue specimens. The bone
      fragments had mild purulent osteomyelitis associated with numerous gram-positive
      rods and cocci. The dog was successfully treated by surgical debridement of the
      lesion and clindamycin administration.

PMID- 1399799
TI  - Reversible megaesophagus associated with atypical primary hypoadrenocorticism in
      a dog.
AB  - Megaesophagus, hypercalcemia, and eosinophilia associated with glucocorticoid
      deficiency were detected in a 5-year-old neutered female Standard Poodle with
      concurrent hypothyroidism. Clinical and biochemical abnormalities resolved with
      glucocorticoid replacement treatment, and the dog was normal 29 months after
      diagnosis. The dog's breed and sex and the existence of a second endocrinopathy
      supported an underlying immunologic disorder.

PMID- 1399800
TI  - Treatment of a mandibular bone cyst by use of a corticocancellous bone graft in a
      horse.
AB  - A 1-year-old Appaloosa stallion had a mass on the right rostral hemimandible. The
      mass was firm, did not cause signs of pain, and was identified as a bone cyst by
      radiography and biopsy. Surgical correction included curettage of the cystic
      cavity and grafting the defect with both cortical and cancellous bone. By 5
      months, the cystic cavity was ossifying; continued remodeling with an increase in
      bone density was apparent 22 months after surgery.

PMID- 1399801
TI  - Stabilization of a proximal femoral physeal fracture in a filly by use of
      cancellous bone screws.
AB  - A Salter-Harris type-II fracture of the proximal portion of the right femur in a
      2-month-old filly was reduced and stabilized with three 6.5-mm-diameter, 100-mm
      long cancellous bone screws through a dorsal approach to the right coxofemoral
      joint. The screws were removed after 11 months because the filly became lame in
      the affected limb. The surgical wounds dehisced despite preventive measures, most
      likely because of tightness of skin in the coxal region. Seven years after the
      original injury, the horse could perform vigorous paddock exercise without any
      disability. Early internal fixation of proximal femoral physeal fractures in
      foals can provide a good long-term prognosis.

PMID- 1399802
TI  - Antemortem diagnosis of cholangiocellular carcinoma in a horse.
AB  - A 10-year-old Tennessee Walking Horse gelding was admitted to the veterinary
      teaching hospital for evaluation of intermittent fever, lethargy, and anorexia.
      Initial laboratory analyses revealed anemia and hyperfibrinogenemia.
      Abdominocentesis and thoracentesis yielded fluid samples with high nucleated cell
      counts and total protein concentrations. The tentative diagnosis was nonseptic
      peritonitis. The horse did not improve after 4 days of antimicrobial treatment,
      and pitting edema of the ventral midline developed. Thoracic radiography and
      ultrasonography revealed consolidation of the ventral aspect of the lung fields
      and pleural effusion. Pleuroscopy of the right hemithorax revealed pleural
      effusion and a soft-tissue mass in the caudal portion of the mediastinum.
      Findings on biopsy of the liver and mediastinal mass led to a presumptive
      diagnosis of metastatic cholangiocellular carcinoma. The horse was euthanatized,
      and the diagnosis was confirmed at necropsy.

PMID- 1399803
TI  - Focal premature physeal closure (hyena disease) in calves.
AB  - Focal premature closure of long-bone physes was the cause of conformational
      abnormalities that affected about 1% of a herd of dairy replacement calves.
      Affected calves were noticed to "bunny hop" by 3 months of age, and by 6 months
      of age, they developed abnormal conformation characterized by short pelvic limbs.
      This condition resembled "hyena disease," which has been described in dairy
      calves in Europe and Japan. With the exception of the aforementioned
      abnormalities and femoropatellar joint distention, a group of 5 affected calves
      examined were clinically normal. At necropsy, focal to almost complete closure of
      physes was found in the humeri, tibias, and femurs. Cause was not established for
      the condition; however, it was discovered that the calves had been given
      supplemental vitamin A/D3 in amounts greater than 10 times those recommended.

PMID- 1399804
TI  - Polycystic kidney disease and renal lymphoma in a cat.
AB  - A 2-year-old castrated domestic shorthair cat was determined to have polycystic
      kidney disease (PKD) and renal lymphoma. History and examination findings
      consisted of progressive lethargy, asymmetric renomegaly, thick segments of small
      intestine, and anisocoria. Initial diagnostic tests revealed nonregenerative
      anemia, mild azotemia, and multiple, round anechoic cysts in both kidneys. Renal
      cystic fluid contained many mature lymphocytes, and results of biochemical
      analysis indicated that the fluid was consistent with proximal tubular fluid.
      Stage-3 lymphoma was diagnosed on the basis of histologic evidence of
      unresectable lymphoma in multiple abdominal organs. Chemotherapy with vincristine
      sulfate, cytarabine, cyclophosphamide, and prednisone was unsuccessful.
      Morphologic association between PKD and lymphoma could not be identified after
      histologic evaluation of the kidneys.

PMID- 1399805
TI  - Coccidioidomycosis in horses: 15 cases (1975-1984).
AB  - Fifteen confirmed cases of equine coccidioidomycosis that originated in
      California and Arizona were studied retrospectively. Age, breed, and sex varied
      among affected horses. The most common historical problems were chronic weight
      loss (53% of cases) and persistent cough (33% of cases). The most frequent
      physical examination abnormalities were related to the respiratory tract (60% of
      cases). In 27% of cases, horses had signs of musculoskeletal pain. Horses
      consistently had hyperproteinemia, hyperfibrinogenemia, leukocytosis, and
      neutrophilia. An antemortem etiologic diagnosis was made for 11 (73%) horses, all
      of which had positive serologic tests for coccidioidomycosis. Of the seropositive
      horses, 5 (46%) also had positive cultures for Coccidioides immitis. One horse
      died naturally. The other 14 were euthanatized. Prolonged treatment with specific
      antifungal agents was attempted in 4 horses without apparent benefit. Postmortem
      abnormalities included pulmonary parenchymal lesions (64% of cases), thoracic
      lymphadenopathy (57% of cases), hepatic parenchymal involvement (43% of cases),
      and osteomyelitis (29% of cases). The lesions were granulomatous or
      pyogranulomatous and C immitis was observed microscopically in 83% of cases.

PMID- 1399806
TI  - Cutaneous actinomycosis and nocardiosis in dogs: 48 cases (1980-1990).
AB  - Medical records of 48 dogs with cutaneous actinomycosis or nocardiosis were
      reviewed. Male, large-breed dogs kept outdoors were overrepresented. The mean age
      at admission was 3.6 years. Cutaneous swelling (68%), abscesses (65%), draining
      tracts (48%), fever (36%), and signs of pain (13%) were the most common clinical
      findings. The cervicofacial area was affected in 48% of the dogs. Abdominal and
      thoracic wall involvement was less common. Leukocytosis, neutrophilia with left
      shift, monocytosis, and hyperglobulinemia were common. The diagnosis was
      confirmed by cytologic examination, bacteriologic culture, or histologic
      examination. Gram-positive filamentous bacteria were seen in 69% of the fine
      needle aspirates and in 50% of the biopsy specimens. Actinomyces spp were
      isolated from cutaneous lesions in 27 (60%) dogs. Nocardia asteroides was
      isolated from 1 dog. Treatment consisted of surgical debridement, drainage, and
      administration of antibiotics in 29 dogs (group A) and antibiotics alone in 13
      dogs (group B). The infection redeveloped in 10 (42%) group-A dogs and 6 (60%)
      group-B dogs. Of the 10 group-A dogs with recurrent infection, 6 had resolution
      after a second surgery and 4 were euthanatized. Of the 6 group-B dogs, 1 had
      resolution after surgery, 4 were euthanatized or died because of persistent
      disease, and 1 had an unresolved infection. The combination of surgery and
      antibiotic treatment appeared to be superior to antibiotic treatment alone in
      resolving cutaneous Actinomyces and Nocardia infections.

PMID- 1399807
TI  - Lens-induced uveitis in dogs: 151 cases (1985-1990).
AB  - During a 5-year period, phacolytic uveitis was diagnosed in 202 eyes of 151 dogs
      admitted to the veterinary teaching hospital. The diagnosis of phacolytic uveitis
      was based on the finding of a cataractous lens and anterior uveitis, unassociated
      with other identifiable causes of uveal inflammation. The most commonly affected
      breeds were the Toy and Miniature Poodle (35%) and the American Cocker Spaniel
      (19%). The mean age was 7.0 years for all breeds, 5.1 years for the Cocker
      Spaniel, and 9.0 years for the Poodle breeds. Evidence of cataract resorption was
      visible in 72% of the eyes. Fifty-one dogs were affected bilaterally and 100 dogs
      unilaterally. The mean interval between recognition of the cataract and the onset
      of lens-induced uveitis (LIU) was 17 months; mean times of 25 and 11 months were
      seen in the Poodle breeds and American Cocker Spaniel, respectively. The mean age
      of dogs requiring greater than 1 revisit before the inflammation had subsided was
      5.5 years. Complications, referable to the uveitis, were seen in 14% of eyes, the
      most important of which were glaucoma (16 eyes) and phthisis bulbi (9 eyes). Lens
      extraction surgery was done on 50 LIU-affected eyes, and on 35 normal eyes in LIU
      affected animals. The 2- and 6-month success rates for LIU-affected eyes were 78
      and 39%, respectively, and for normal eyes in LIU-affected animals were 85 and
      71%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399808
TI  - What is your diagnosis? Fragmented medial coronoid process.

PMID- 1399810
TI  - Perceived differences in the importance and frequency of practice of clinical
      teaching behaviors.
AB  - The purpose of this study was to identify whether or not discrepancies existed
      between the importance of clinical teaching behaviors and the frequency with
      which those behaviors were practiced in the clinical setting. Surveys listing
      clinical teaching behaviors were distributed to preceptors and their students.
      Both groups completed the survey twice, ranking their perception of the
      importance of each behavior, as well as the frequency with which it was practiced
      in the clinical setting. Four different allied health disciplines from four, four
      year undergraduate institutions in Ohio participated in the study. Means and
      standard deviations were calculated for each item. Two-tailed t-tests were
      applied to each set of responses, with p < 0.05 considered statistically
      significant. Results revealed that while both students and preceptors agreed on
      the importance of the items, they differed significantly (p < 0.05) with regard
      to the frequency with which effective clinical teaching behaviors were practiced.

PMID- 1399809
TI  - The Americans with Disabilities Act: new challenges for the health professions.

PMID- 1399811
TI  - Job orientation and motivation of cytotechnologists.
AB  - Little is known about what motivates cytotechnologists as a distinct group. The
      Job Attitude Survey (JAS), developed by Shoukry Saleh, was applied to a cohort of
      261 cytotechnologists. The group was divided between nondegreed cytotechnologists
      (CTs) (n = 97) and bachelor's degreed cytotechnologists (BSCTs) (n = 164) to see
      if there were noticeable motivational differences between the two. No statistical
      difference was found between the two groups. Compared to other groups of
      professionals who had previously taken the JAS, cytotechnologists ranked
      responsibility as a very low factor, demonstrating that it does not function as a
      motivator. In contrast, salary was ranked very high by cytotechnologists,
      suggesting it functions as a large dissatisfier. Based upon these findings,
      educational attainment changes the cytotechnologists' attitude very little. The
      findings are also consistent with the views that JAS-type surveys are important
      and that both motivators and dissatisfiers should be addressed in order to
      improve retention of cytotechnologists.

PMID- 1399813
TI  - Strengths and weaknesses of allied health special project grant applications.

PMID- 1399812
TI  - Differences in innovation-related characteristics between singleskilled and
      multiskilled health practitioner educational programs.
AB  - A survey of educational programs preparing single- and multiskilled health
      practitioners was conducted to determine the predictive power of organizational
      formalization and centralization and individual program director cosmopolitanism
      (ie, orientation to their larger profession as opposed to local environment) upon
      readiness to innovate for the educational units. Questionnaires were sent to 45
      directors of programs preparing multiskilled health practitioners and 49
      directors of programs preparing singleskilled health practitioners. Results
      indicated no significant differences between program directors of single- and
      multiskilled programs in their perceptions of the readiness to innovate for their
      educational units. Regression analysis indicated that a decentralized
      organization was a predictor of an educational unit's readiness to innovate. This
      finding held for both single- and multiskilled programs. Although cosmopolitanism
      was not a significant predictor of readiness to innovate, program directors at
      four-year institutions had a significantly higher level of that characteristic
      than directors at two-year institutions. The results of this study, although
      limited by individual and not multiple responses from each institution, do not
      indicate any differences in the ability of organizational formalization and
      centralization to predict the innovative characteristics of single- and
      multiskilled allied health programs. Additionally, the cosmopolitanism of program
      directors also does not predict these same characteristics.

PMID- 1399814
TI  - Health promotion and disease prevention: will eastern Europe follow the lead?

PMID- 1399815
TI  - Medium-term carcinogenicity bioassay.

PMID- 1399816
TI  - Environmental and physiological influences on human natural killer cell activity
      in relation to good health practices.
AB  - We examined the association of natural killer (NK) cell activity with a number of
      life style factors by a cross-sectional analysis on 2892 Japanese individuals.
      The following habits were found to be associated with increased NK activity: 1)
      alcohol drinking (males, P less than 0.05), 2) not smoking cigarettes (males and
      females, P less than 0.001), 3) increased intake of green vegetables (females, P
      less than 0.001), 4) increased intakes of meat, milk, dairy products, and soybean
      products (males, P less than 0.01), 5) daily workload of less than 3 hours per
      day (females, P less than 0.05), 6) regular meals (females, P less than 0.05), 7)
      regular sleep of more than 7 hours (females, P less than 0.05), 8) proper body
      weight. In addition, systolic blood pressure showed a positive correlation with
      NK activity (P less than 0.001), while proportion of helper/inducer (OKT4+) T
      cells and fraction of beta-globulin showed negative correlations (P less than
      0.001). We thus found that the living habits associated with increased NK
      activity were consistent with generally accepted good health practices, except
      alcohol drinking.

PMID- 1399817
TI  - Cigarette smoking, alcohol use and adenomatous polyps of the sigmoid colon.
AB  - The relationship of adenomatous polyps of the sigmoid colon with cigarette
      smoking and alcohol use was investigated in male self-defense officials in Japan.
      In the comparison between 116 cases and 930 controls, total ethanol intake was
      not at all associated with the risk of adenomatous polyps, but cigarette smoking
      was strongly related to adenomatous polyps. After adjustment for total ethanol
      intake, body mass index and rank, odds ratios (and 95% confidence interval) for
      the categories of 0, 1-399, 400-799, and 800 or more cigarette-years were 1.0
      (referent), 2.3 (1.1-4.6), 2.9 (1.5-5.4) and 3.2 (1.6-6.5), respectively. Among
      five alcoholic beverages (sake, shochu, beer, whiskey including brandy, and
      wine), only whiskey consumption was weakly related to the risk of adenomatous
      polyps. Because the present findings disagree with an earlier observation on self
      defense officials, we examined the association with smoking and alcohol use
      separately for small (less than 5 mm) and large (greater than or equal to 5 mm)
      adenomas, combining data from these two studies. Cigarette smoking was more
      strongly associated with small adenomas while the positive association with
      certain alcoholic beverages were largely confined to large adenomas. These
      findings suggest that cigarette smoking and alcohol use may be linked with the
      development of adenoma at different stages of colon tumorigenesis.

PMID- 1399818
TI  - Modifying effects of various chemicals on tumor development in a rat wide
      spectrum organ carcinogenesis model.
AB  - The efficacy of a wide-spectrum organ carcinogenesis model for detection of
      modification potential of exogenous agents was investigated in F344 male rats.
      Groups of animals were sequentially injected with N-bis(2
      hydroxypropyl)nitrosamine (1000 mg/kg body weight, i.p., in saline, twice in week
      1), N-ethyl-N-hydroxyethylnitrosamine (1500 mg/kg body weight, i.g., in distilled
      water, twice in week 2) and 3,2'-dimethyl-4-aminobiphenyl (75 mg/kg body weight,
      s.c., in corn oil, twice in week 3) for wide-spectrum initiation of target organs
      and then given one of 10 test chemicals, comprising 6 hepatocarcinogens and 4 non
      hepatocarcinogens, for 12 weeks. All 10 chemicals exerted modifying effects in
      their respective target organs. Enhancing influence could be detected in the
      liver and urinary bladder with 2-acetylaminofluorene, ethionine, and 3'-methyl-4
      dimethylaminoazobenzene; in the liver and thyroid with 4,4'
      diaminodiphenylmethane and phenobarbital; in the esophagus and urinary bladder
      with N-butyl-N-(4-hydroxybutyl)nitrosamine; in the forestomach and urinary
      bladder with butylated hydroxyanisole; in the liver with 7,12
      dimethylbenz[a]anthracene and in the liver and lung with 3-methylcholanthrene.
      Inhibitory effects on development of glutathione S-transferase placental form
      positive liver cell foci were observed with clofibrate. The results indicate that
      the present model can be reliably utilized as a whole body medium-term bioassay
      system for assessment of environmental cancer modifiers.

PMID- 1399820
TI  - Inhibitory effect of cryptoporic acid E, a product from fungus Cryptoporus
      volvatus, on colon carcinogenesis induced with N-methyl-N-nitrosourea in rats and
      with 1,2-dimethylhydrazine in mice.
AB  - The antitumorigenic effect of cryptoporic acid E (CPA-E), a dimeric drimane
      sesquiterpenoid isolated from the fungus Cryptoporus volvatus, on colon
      carcinogenesis was investigated. Female F344 rats given an intrarectal
      instillation of 2 mg of N-methyl-N-nitrosourea 3 times weekly in weeks 1 and 2
      were fed diet containing 0.2% CPA-E from week 3. Female ICR mice given 15 weekly
      intraperitoneal injections of 10 mg of 1,2-dimethylhydrazine/kg body weight
      during weeks 1 to 15 were fed diet containing 0.06% CPA-E from week 1. The
      experiment was terminated at week 35 for rats and at week 25 for mice. The
      incidence and the number of tumors per animal were reduced in CPA-E-fed animals
      compared to the controls: 31% vs. 75% (P less than 0.05) and 0.4 +/- 0.2 (SEM)
      vs. 0.9 +/- 0.2 (0.1 greater than P greater than 0.05) in rats, and 31% vs. 63%
      (0.1 greater than P greater than 0.05) and 0.4 +/- 0.2 vs. 2.4 +/- 0.8 (P less
      than 0.05) in mice (16 animals in each group). Intrarectal deoxycholic acid
      induced colonic mucosal ornithine decarboxylase activity was significantly
      lowered in CPA-E-fed animals compared to controls. This shows an antipromoting
      activity of CPA-E against colon carcinogenesis. Thus, it was concluded that CPA-E
      inhibits colon cancer development in both rats and mice treated with 2 different
      colon carcinogens.

PMID- 1399819
TI  - Inorganic alkalizers and acidifiers under conditions of high urinary Na+ or K+ on
      cell proliferation and two-stage carcinogenesis in the rat bladder.
AB  - Effects of alkalizers and acidifiers on bladder cell proliferation and two-stage
      carcinogenesis were investigated under conditions of high urinary Na+ or K+.
      Animals were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking
      water for 4 weeks and then received Na3PO4, NaH2PO4, NaCl, NaH2PO4 + NaCl, K3PO4,
      KH2PO4, KCl, KH2PO4 + KCl or no chemical supplement in the diet from weeks 5 to 8
      and from weeks 12 to 20. During weeks 9 to 11, the rats were fed 3% uracil in
      their diet for acceleration of promotion. Na3PO4 or K3PO4 induced marked
      natriuresis or kaluresis and alkalinuria associated with strong promoting
      potential for bladder carcinogenesis. NaH2PO4 induced moderate natriuresis and
      aciduria and exhibited weak promoting activity. NaH2PO4 + NaCl or KH2PO4 + KCl
      caused marked increase in the respective cation levels and aciduria with
      elevation of promotion as compared to NaH2PO4 or KH2PO4 alone. NaCl or KCl
      induced moderate natriuresis or kaluresis and did not alter urinary pH. NaCl but
      not KCl also exerted weak promoting activity for bladder carcinogenesis.
      Increased DNA synthesis after test chemical exposure for 8 weeks and
      morphological alterations observed by scanning electron microscopy in the bladder
      epithelium were only quantitatively linked with promoting activity in the Na3PO4
      case. With the other treatments no clear correlation between early cell
      proliferation and promotion potential was apparent. The present results suggest
      that although elevation in urinary Na+ or K+ level may be an essential factor for
      promotion of rat bladder carcinogenesis, the action of these cations may depend
      strongly on urinary alkalinity.

PMID- 1399821
TI  - Inhibitory effects of the natural products indole-3-carbinol and sinigrin during
      initiation and promotion phases of 4-nitroquinoline 1-oxide-induced rat tongue
      carcinogenesis.
AB  - The modifying effects of indole-3-carbinol (I3C) and sinigrin (SIN) on the
      initiation and post-initiation phases of tongue carcinogenesis induced by 4
      nitroquinoline 1-oxide (4-NQO) were investigated in male ACI/N rats. Rats were
      divided into eight groups: group 1 was given 4-NQO (10 ppm) in the drinking water
      for 12 weeks, starting at 7 weeks of age; groups 2 and 3 were given 4-NQO and fed
      the diets containing I3C (1,000 ppm) and SIN (1,200 ppm) for 14 weeks,
      respectively, starting at 6 weeks of age; groups 4 and 5 were given 4-NQO and
      then they were fed I3C and SIN containing diets for 23 weeks, respectively,
      starting one week after 4-NQO exposure; groups 6 and 7 were given I3C and SIN
      alone, respectively, during the experiment; group 8 served as an untreated
      control. At the termination of the experiment (week 37), the incidence of tongue
      neoplasms (squamous cell papilloma and carcinoma) in group 2 (1/15, 7%), group 3
      (1/15, 7%), group 4 (3/15, 20%) or group 5 (2/15, 13%) was significantly smaller
      than that in group 1 (12/17, 71%) (P = 0.0003, P = 0.005 or P = 0.002). No tongue
      carcinomas developed in rats of groups 2, 3, and 5. Similarly, the incidence of
      preneoplastic lesions (hyperplasia and dysplasia) of the tongue in group 2
      (11/15, 73%), group 3 (10/15, 67%), group 4 (11/15, 73%) or group 5 (10/15, 67%)
      was significantly lower than that in group 1 (17/17, 100%) (P = 0.04 or P =
      0.02). There were no tongue neoplasms in rats of groups 6, 7, and 8.
      Administration of I3C and SIN also caused significant decreases in the number and
      area of silver-stained nucleolar organizer regions protein (AgNORs), a new cell
      proliferation index, of tongue squamous epithelium. Thus, I3C and SIN inhibited
      rat tongue carcinogenesis in both the initiation and post-initiation phases, when
      administered in these respective phases together with, or following treatment
      with, 4-NQO.

PMID- 1399822
TI  - Strain difference of susceptibility to 4-nitroquinoline 1-oxide-induced tongue
      carcinoma in rats.
AB  - Strain difference of susceptibility to 4-nitroquinoline 1-oxide (4NQO)-induced
      squamous cell carcinomas of the tongue among Dark-Agouti, Long-Evans, Sprague
      Dawley, ACI/Ms, Fischer 344, Donryu and Wistar/Furth rats was surveyed by
      evaluating the survival times, incidences and sizes of developed tumors as
      markers of susceptibility. Administration of 4NQO dissolved in drinking water
      induced squamous cell carcinomas in various sites of the upper digestive tract
      mucosa of all the experimental male and female rats of the seven strains.
      Regarding the mean survival times, Wistar/Furth rats survived much longer than
      any other strain of rats, and Dark-Agouti showed the shortest survival. The
      incidence of large, mass-type carcinomas of the tongue of Dark-Agouti rats was
      higher than in any other strain of rats, while that of Wistar/Furth rats was the
      lowest. Subsequently the mitotic activity and bromodeoxyuridine incorporation in
      the tongue epithelium of Dark-Agouti and Wistar/Furth rats were estimated after a
      short-term administration of 4NQO. There was a pronounced difference between the
      two strains of rats, because the proliferative responses of the tongue epithelium
      of Dark-Agouti rats to the 4NQO stimulation were much higher than those of
      Wistar/Furth rats. These results indicated that there are marked differences in
      the susceptibility to 4NQO-induced tongue carcinoma among the seven strains of
      rats, and that Dark-Agouti and Wistar/Furth rats could be useful as models of
      highly and poorly susceptible strains, respectively, for further genetic
      analysis.

PMID- 1399823
TI  - High susceptibility to lung cancer analyzed in terms of combined genotypes of
      P450IA1 and Mu-class glutathione S-transferase genes.
AB  - Lung cancer is closely associated with cigarette smoking. Aromatic hydrocarbons
      in smoke, including benzo[a]pyrene, first require metabolic activation by Phase I
      enzymes, cytochrome P450, to their ultimate forms, and these activated forms are
      then subjected to detoxification by Phase II enzymes, especially glutathione S
      transferases. Thus, genetically determined susceptibility to lung cancer may
      depend on the metabolic balance between Phase I and Phase II enzymes. In this
      study, we identified individuals genetically at high risk of lung cancer in terms
      of polymorphisms of the P450IA1 gene and GST1 gene. The relative risk of
      individuals with a combination of the genotypes of both a homozygous rare allele
      of the P450IA1 gene and the nulled GST1 gene was remarkably high at 5.8 for lung
      cancer and 9.1 for squamous cell carcinoma compared with other combinations of
      genotypes.

PMID- 1399824
TI  - Deficiency of beta 1-6 N-acetylglucosaminyltransferase involved in the
      biosynthesis of blood group I antigen in the liver of LEC rats.
AB  - The activities of the beta 1-6 and beta 1-3 N-acetylglucosaminyltransferase,
      which synthesize blood group I and i antigens, respectively, were measured in
      various tissues of hepatitis- and hepatoma-predisposed rats (LEC rats). In LEC
      rats the beta 1-6 N-acetylglucosaminyltransferase activity was barely detectable
      in the liver, while substantial enzyme activity was found in other tissues. In
      the control LEA rats the enzyme was expressed in most tissues, including the
      liver. Immunochemical studies using a monoclonal antibody which recognizes I
      antigen indicated that the expression of I antigen was less prominent in
      hepatocytes of LEC rats than in hepatocytes of LEA rats. The level of beta 1-3 N
      acetylglucosaminyltransferase activity was constant in most of the tissues during
      the development. These results indicate that the biosynthesis of I antigen does
      not occur in the livers of the LEC rats.

PMID- 1399826
TI  - Production of human immunoglobulin G reactive against human cancer in tumor
      bearing mice with severe combined immunodeficiency reconstituted with human
      splenic tissues.
AB  - Splenic tissues derived from patients with gastric cancer were implanted into
      mice with severe combined immunodeficiency (SCID) and then the mice were
      challenged with COLO-205, a human colon cancer cell line. Production of human
      immunoglobulin G (IgG) reactive against the COLO-205 cells was detected by enzyme
      linked immunosorbent assay in sera from the reconstituted and tumor-bearing SCID
      mice. The titers of the reactive IgG relative to total IgG in the sera of SCID
      mice began to increase from one week after implantation of the tumor cells, and
      became 10- to 100-fold higher than that in the donor's serum by 3-4 weeks. This
      model using implantation of human cancer cells in SCID mice reconstituted with
      human splenic tissues would facilitate further studies of human cancer
      immunology.

PMID- 1399825
TI  - Triflavin, an Arg-Gly-Asp-containing antiplatelet peptide inhibits cell
      substratum adhesion and melanoma cell-induced lung colonization.
AB  - Triflavin, an Arg-Gly-Asp (RGD) containing peptide purified from Trimeresurus
      flavoviridis snake venom, inhibits human platelet aggregation by blocking
      fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa
      complex. In this study, we show that triflavin (1-30 micrograms/mouse) inhibits
      B16-F10 melanoma cell-induced lung colonization in C57BL/6 mice in a dose
      dependent manner. In vitro, triflavin dose-dependently inhibits adhesion of B16
      F10 melanoma cells to extracellular matrices (ECMs; i.e., fibronectin,
      fibrinogen, vitronectin, and collagen type I). Triflavin is approximately 600-800
      times more potent than GRGDS at inhibiting cell adhesion. In addition, triflavin
      dose-dependently inhibits B16-F10 cell-induced platelet aggregation. These
      results imply that the inhibitory effect of triflavin on the adhesion of tumor
      cells to ECMs (e.g., fibronectin, vitronectin and collagen type I) and/or tumor
      cell-induced platelet aggregation may be partially responsible for its
      antimetastatic activity in C57BL/6 mice.

PMID- 1399828
TI  - Potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea's toxicity in vitro
      by two new bioreductive agents.
AB  - Two new bioreductive compounds, 9-[3-(2-nitro-1-imidazolyl)propylamino]acridine
      hydrochloride (NLA-1) and 9-[2-(2-nitro-1-imidazolyl)ethylamino]acridine
      hydrochloride (NLA-2), which behave as hypoxic cytotoxins and radiosensitizers,
      have been investigated for potentiation of 1-(2-chloroethyl)-3-cyclohexyl-1
      nitrosourea's (CCNU) cytotoxic activity in vitro using V-79 cells. The
      preincubation effect as well as conditions of coadministration of CCNU with each
      sensitizer have been examined. In this latter case, the median-effect analysis
      was applied to evaluate whether the phenomenon was additive or synergistic. A
      clonogenic assay was used to score survival. Both bioreductive compounds, even at
      very low concentrations, significantly enhance the cytotoxic activity of CCNU
      under conditions of hypoxic preincubation. The enhancement of CCNU cytotoxicity
      is dependent upon preincubation time and the concentrations of both CCNU and the
      specific bioreductive agent. Coincubation of cells under hypoxia with CCNU and
      each bioreductive agent led to some potentiation, but only at lower survival
      levels. No chemosensitization was observed under aerobic conditions with either
      sensitizer.

PMID- 1399827
TI  - Polyoxyethylene-modified superoxide dismutase reduces side effects of adriamycin
      and mitomycin C.
AB  - Polyoxyethylene-modified superoxide dismutase (SOD-POE) is a newly developed long
      acting superoxide dismutase. Adriamycin (ADR) and mitomycin C (MMC) generate
      superoxide, which contributes to their cytocidal effects or side effects. We
      examined whether SOD-POE could prevent the side effects induced by superoxide
      generated by antitumor agents, and the following results were obtained. SOD-POE
      did not influence the antitumor effects of ADR and MMC either in vitro or in
      vivo, but prevented the toxic death of BALB/c, nu/nu male mice caused by
      overdoses of ADR or MMC. As for its effective sites, SOD-POE prevented a decrease
      in the specific activity of rotenone-sensitive NADH-ubiquinone oxido-reductase
      (complex I) in heart muscle mitochondrial respiratory chain function in BALB/c
      male mice administered 10 mg/kg ADR, and prevented damage to the sarcoplasmic
      reticulum and mitochondria of mouse heart muscle by ADR as observed by electron
      microscopy. Furthermore, SOD-POE prevented bone marrow suppression induced by MMC
      in Donryu rats. The above results suggest that combination chemotherapy with SOD
      POE would make it possible to increase the maximum permissible doses of antitumor
      agents, improving the efficacy of these agents.

PMID- 1399829
TI  - Polyamines in ejaculated ram spermatozoa and their relationship with sperm
      motility.
AB  - Intracellular polyamine levels in ejaculated spermatozoa and seminal fluid from
      rams were determined by fluorescent spectroscopy of their dansyl derivatives.
      Relationships between the sperm polyamine content and sperm motility of six
      mature and eight pubescent rams were studied. Samples were collected from both
      groups once a month from August through October. Mature rams had a greater
      percentage of motile sperm cells than lambs (94% versus 73% in September and 92%
      versus 78% in October); higher spermidine content (36 versus 9 pmol/10(8) cells
      in September and 162 versus 55 pmol/10(8) cells in October); higher spermine
      content (984 versus 205 pmol/10(8) cells in September and 1,229 versus 414
      pmol/10(8) cells in October); and higher total sperm polyamine content (1,021
      versus 216 pmol/10(8) cells in September and 2,258 versus 973 pmol/10(8) cells in
      October). In the lambs, spermidine content increased (55 versus 9 pmol/10(8)
      cells); spermine content increased (414 versus 205 pmol/10(8) cells); and total
      sperm polyamine content increased (973 versus 215 pmol/10(8) cells) in October
      compared to September. Ejaculates with sperm motility higher than 85% had greater
      spermine (848 versus 234 pmol/10(8) cells in September and 1064 versus 449
      pmol/10(8) cells in October), and total sperm polyamine content (882 versus 244
      pmol/10(8) cells in September and 2,015 versus 1,008 pmol/10(8) cells in October)
      than ejaculates with less than 450 pmol total sperm polyamines/10(8) cells was
      68% +/- 6% compared to 90% +/- 4% in cells with greater than 450 pmol (average
      for all ejaculates) total sperm polyamines/10(8) cells. These data suggest a
      positive relationship between sperm polyamine constant and sperm
      motility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399830
TI  - A long-term, prospective study of the physiologic and behavioral effects of
      hormone replacement in untreated hypogonadal men.
AB  - This study describes sexual activity, nocturnal penile erections, and mood states
      as a function of serum levels of androgens in previously untreated hypogonadal
      men before and during hormone replacement, selected infertile men (elevated serum
      follicle-stimulating hormone levels), and normal men. Nocturnal penile tumescence
      and rigidity were measured with a portable monitor, and sexual activity and mood
      were assessed by prospective, self-reported written forms. Nocturnal erections
      were absent or of very low amplitude and duration in the untreated hypogonadal
      men compared to the infertile and normal men. Nocturnal erections increased
      steadily during hormone replacement and were in the normal range within 6 to 12
      months of treatment. In contrast, serum testosterone concentration rapidly
      reached the upper range of normal. During treatment, the hypogonadal men reported
      increases in several aspects of sexual activity, including sexual interest and
      the number of spontaneous erections. On mood inventories, the untreated
      hypogonadal men scored significantly higher in ratings of depression, anger,
      fatigue, and confusion than did infertile and normal men. During hormonal
      replacement therapy these scores decreased, although the hypogonadal men
      continued to score higher in "depression" than did infertile and normal men. In
      most instances, the men with infertility and the normal men were statistically
      indistinguishable in nocturnal penile tumescence and rigidity parameters, self
      reported sexual activity, and mood state. These data support the hypothesis that
      androgen treatment increases nocturnal and spontaneous erections, and sexual
      interest, and has some capacity to improve mood.

PMID- 1399831
TI  - Adenosine triphosphate (ATP) concentrations and ATP/adenosine diphosphate ratios
      in human sperm of normospermic, oligospermic, and asthenospermic specimens and in
      their swim-up fractions: lack of correlation between ATP parameters and sperm
      creatine kinase concentrations.
AB  - The authors had previously found an inverse correlation between per sperm
      creatine phosphokinase activity and sperm concentrations in men. Because creatine
      phosphokinase is a key enzyme in sperm energy transport, the possible
      relationship of sperm creatine phosphokinase activity, sperm adenosine
      triphosphate (ATP) concentrations, sperm ATP/ADP (adenosine diphosphate) ratios,
      and computer-aided semen analysis sperm motility parameters were then studied.
      The ATP concentrations and ATP/ADP ratios, measured by high-pressure liquid
      chromatography in washed sperm, were similar in normospermic and oligospermic
      specimens (ATP: 123.1 +/- 21.6 vs. 90.0 +/- 24.5 pmol/10(6) sperm; ATP/ADP: 2.8
      +/- 0.4 vs. 2.1 +/- 0.4, N = 32 and 17, mean +/- SEM), and in samples with normal
      and less than 40% sperm motility (ATP: 96.8 +/- 27.2 vs. 122.2 +/- 19.6
      pmol/10(6) sperm; ATP/ADP: 2.4 +/- 0.5 vs. 2.8 +/- 0.4, n = 26 and 23). In the
      swim-up sperm fractions, which showed improved motility, the ATP concentrations,
      but not the ATP/ADP ratios, were lower than in the initial semen samples (ATP:
      152.9 +/- 28.4 vs. 90.3 +/- 10.6 pmol/10(6) sperm, P less than 0.05; ATP/ADP: 3.3
      +/- 0.5 vs. 3.9 +/- 0.7, N = 18 pairs of samples). This is consistent with our
      previous finding of a lower cytoplasmic content in sperm in swim-up
      fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399832
TI  - Oligotriche and quaking gene mutations. Phenotypic effects on mouse
      spermatogenesis and testicular steroidogenesis.
AB  - The phenotypic actions of the oligotriche gene mutation on testicular function
      have not been elucidated, although it is known that male mice homozygous for the
      mutation are infertile. In the present study, the effect of the oligotriche gene
      mutation on mouse testicular function was analyzed by comparing normal and mutant
      mice. Spermatogenesis was analyzed by enumerating germ cells in seminiferous
      tubules at specific stages of spermatogenesis and by electron microscopy.
      Steroidogenic potential was estimated by radioimmunometric determination of
      testosterone secreted by testes perfused in vitro. Parallel studies were
      completed for male mice homozygous for the quaking gene mutation, a mutation
      known to cause male mouse sterility by disrupting sperm tail development. The
      experimental results suggest that the oligotriche and quaking gene mutations
      interfere with sperm tail formation by different mechanisms. Testicular
      steroidogenesis was not affected by either gene mutation. The results provide the
      first evidence that the oligotriche gene mutation induces male mouse sterility by
      effecting the complete absence of a sperm tail. This phenotypic action is
      different from that of the quaking gene mutation.

PMID- 1399833
TI  - Developmental expression of multiple forms of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase mRNA in rat testes.
AB  - The developmental expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase, the enzyme that catalyzes the rate-limiting reaction of mevalonate
      formation, was investigated in rat testes. Adult testes were found to contain
      three distinct forms of HMG-CoA reductase mRNA of 4.8, 4.2, and 4.0 kilobases
      (kb) in length. In testes from 26-day-old rats the 4.8-kb species was the major
      form present. By 40 days of age, large increases in the levels of the testes
      specific 4.2- and 4.0-kb forms occurred, with a small decrease in the amount of
      the 4.8-kb form. The level of the 4.8-kb form appeared to be associated with the
      level of testicular HMG-CoA reductase activity.

PMID- 1399834
TI  - Hyperactivated motility is coupled with interdependent modifications at axonemal
      and cytosolic levels in human spermatozoa.
AB  - Whether the motility characteristics of hyperactivated spermatozoa were
      determined by stable changes at the axonemal level and whether the presence of
      cytosolic factors was required for the expression of these changes was
      investigated. Different degrees of sperm hyperactivation were produced in Percoll
      washed spermatozoa after incubation for 1 hour to 3 hours at 37 degrees C in
      Ham's F-10 supplemented with human blood plasma or fetal cord serum.
      Decomplemented fetal cord serum induced the highest percentage of hyperactivation
      (19 +/- 3%), followed by human plasma (13 +/- 2%). Fetal cord serum that was not
      decomplemented did not induce a level of hyperactivation (1.7 +/- 0.2%)
      significantly different from control levels (0.9 +/- 0.2%). Dialyzed fetal cord
      serum induced intermediate levels of hyperactivation (6 +/- 1%). The motility
      characteristics of demembranated sperm models of hyperactivated spermatozoa
      induced by decomplemented fetal cord serum and nonhyperactivated spermatozoa were
      compared by videomicroscopy and computer-assisted digital image analysis. After
      demembranation with Triton X-100 and reactivation of motility by Mg. adenosine
      triphosphate (Mg.ATP), hyperactivated and nonhyperactivated spermatozoa showed
      similar motility characteristics. However, hyperactivated spermatozoa that were
      demembranated and reactivated in cytosolic extracts from hyperactivated
      spermatozoa had significantly higher (P less than 0.05) linear velocity (33 +/- 4
      mu/sec) and lower linearity (0.23 +/- 0.04) than control spermatozoa that were
      demembranated and reactivated in control cytosolic extracts (velocity = 24 +/- 1
      mu/sec; linearity = 0.32 +/- 0.02). The data suggest that the expression of
      hyperactivated motility requires interdependent changes at the axonemal and
      cytosolic levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399835
TI  - Changes in the hypothalamic-pituitary-gonadal axis in men after cadaver kidney
      transplantation and cyclosporine therapy.
AB  - A variety of plasma androgens, estradiol, follicle-stimulating hormone,
      luteinizing hormone, prolactin, cortisol, and thyroid parameters were examined in
      10 men followed serially before and after cadaver kidney transplantation. Before
      transplantation, plasma testosterone levels were below normal in 8 of the 10 men.
      Free testosterone, follicle-stimulating hormone, and luteinizing hormone were at
      the lower range of normal values, yet plasma estradiol levels were elevated 3
      fold, and prolactin levels were also high. One month after transplantation, all
      hormones measured were suppressed, probably reflecting high-dose steroids and
      multiple-drug regimens used in the period following the operation. After 3
      months, when other immunosuppressants were reduced and cyclosporine dosage was
      stabilized, plasma testosterone, androgens, follicle-stimulating hormone, and
      luteinizing hormone levels were restored toward normal. After 12 months, plasma
      testosterone levels exceeded pretransplant levels. Plasma estradiol and prolactin
      levels dramatically decreased after transplantation and remained in the normal
      range thereafter. These data indicate that abnormalities of plasma estradiol and
      prolactin levels observed in patients with end-stage renal disease are restored
      toward normal after cadaver kidney transplantation. Androgen levels that were
      suppressed in the period immediately after transplantation were restored to
      normal levels in the succeeding months despite chronic usage of cyclosporine,
      suggesting that cyclosporine, in currently used doses, does not prevent the
      restoration of the hypothalamic-pituitary-testicular axis.

PMID- 1399836
TI  - Diffuse lymphoid tissue associated with the human bulbourethral gland. An
      immunohistologic characterization.
AB  - This study investigates the presence and distribution of immunocompetent cells in
      bulbourethral glands obtained from four multiorgan transplant donors. Monoclonal
      antibodies reacting with B (Leu 12+) and T (Leu 4+) cells, suppressor-cytotoxic
      cells (Leu 2+), helper-inducer (Leu 3a+) and natural killer (Leu7+) phenotypes,
      monocyte-macrophages, (LeuM3+), and cells expressing interleukin-2 receptor and
      HLA-DR antigen were tested in all specimens using an indirect immunoperoxidase
      staining procedure. T lymphocytes were estimated to represent 10% of the mucosal
      cell population. Almost all intraepithelial lymphocytes were suppressor-cytotoxic
      (CD8+) cells. The results demonstrate the presence of a defined distribution of
      immunocompetent cells in these sex accessory glands. Their role in combatting
      infections or other chronic genitourinary diseases is still undefined.

PMID- 1399837
TI  - Thiol-disulfide status and acridine orange fluorescence of mammalian sperm
      nuclei.
AB  - The relationship between thiol-disulfide status and acridine orange fluorescence
      of testicular, epididymal, and ejaculated spermatozoa in several mammalian
      species was investigated. Spermatozoa were fixed with acetic alcohol, stained
      with acridine orange, and examined with a fluorescence microscope. The majority
      of the nuclei of testicular spermatozoa of the hamster, mouse, and rabbit
      exhibited red acridine orange fluorescence. The proportion of sperm nuclei with
      red acridine orange fluorescence decreased as the spermatozoa descended the
      epididymis. Red acridine orange fluorescence was replaced by green acridine
      orange fluorescence. The site in the epididymis where 100% of the nuclei
      exhibited green fluorescence was the distal caput in the mouse, the corpus in the
      rabbit, and the proximal cauda in the hamster. In semen samples from men with
      proven fertility, normal semen parameters, or both, about 60% to 90% of the
      nuclei exhibited green acridine orange fluorescence. The proportion of sperm
      nuclei exhibiting green acridine orange fluorescence was higher in the
      spermatozoa pellet (containing highly motile spermatozoa) obtained by
      centrifugation through a Percoll gradient. From experiments using disulfide
      reducing, thiol-oxidizing and thiol-detecting agents, we concluded that sperm
      nuclei fluoresce red when they are treated with acid while their DNA-associated
      protamines are poor in disulfides. Under such conditions, DNA is vulnerable to
      denaturation. Acridine orange binds to denatured (single-stranded) DNA as
      aggregates and emits red fluorescence. In contrast, when sperm nuclei are treated
      with acid while their DNA-associated protamines are rich in disulfides, DNA is
      resistant to denaturation. Acridine orange binds to native (double-stranded) DNA
      as a monomer and emits green fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399838
TI  - Folipastatin, a new depsidone compound from Aspergillus unguis as an inhibitor of
      phospholipase A2. Taxonomy, fermentation, isolation, structure determination and
      biological properties.
AB  - A new inhibitor of phospholipase A2 was isolated from the fermentation broth of
      Aspergillus unguis. The structure, with a depsidone carbon skeleton, was assigned
      by spectroscopic experiments.

PMID- 1399839
TI  - Glisoprenins, new inhibitors of acyl-CoA: cholesterol acyltransferase produced by
      Gliocladium sp. FO-1513. I. Production, isolation and physico-chemical and
      biological properties.
AB  - Gliocladium sp. FO-1513 was found to produce novel inhibitors of acyl-CoA:
      cholesterol acyltransferase (ACAT). Two active compounds, designated glisoprenins
      A and B, were isolated from the culture broth of the producing strain by a
      conventional method. The IC50 values of glisoprenins A and B for ACAT activity
      were 46 and 61 microM in an enzyme assay using rat liver microsomes, and 1.2 and
      0.57 microM in a J774 macrophage assay, respectively.

PMID- 1399840
TI  - New cyclodepsipeptides, enniatins D, E and F produced by Fusarium sp. FO-1305.
AB  - New cyclodepsipeptides named enniatins D, E and F were isolated from the culture
      broth of Fusarium sp. FO-1305 as inhibitors of acyl-CoA:cholesterol
      acyltransferase (ACAT). The respective structures of enniatins D, E and F were
      determined to be cyclo[D-alpha-hydroxyisovaleryl(D-Hiv)-L-N-methylleucinyl(L- Me
      Leu)-D-Hiv-L-N-methylvalinyl(L-Me-Val)-D-Hiv-L-Me-Val], a mixture of cyclo-[D-Hiv
      L-Me-Leu-D-Hiv-L-N-methylisoleucinyl(L-Me-Ile)-D-Hiv- L-Me-Val] and cyclo(D-Hiv-L
      Me-Ile-D-Hiv-L-Me-Leu-D-Hiv-L-Me-Val), and cyclo(D-Hiv-L-Me-Leu-D-Hiv-L-Me-Ile-D
      Hiv-L-Me-Ile) by spectral analyses and chemical degradation. The IC50 values of
      enniatins D, E and F for ACAT activity in an enzyme assay using rat liver
      microsomes were calculated to be 87, 57 and 40 microM, respectively.

PMID- 1399842
TI  - A10255, a complex of novel growth-promoting thiopeptide antibiotics produced by a
      strain of Streptomyces gardneri. Taxonomy and fermentation studies.
AB  - A10255 is a complex of new thiopeptide antibiotics characterized structurally by
      a cyclic peptide core to which is attached a side chain composed of
      dehydroalanine moieties. The complex contained 80-85% factor B, 15-20% factor G,
      and trace amounts of factors C, D, E, F, H, and J. Taxonomic studies indicated
      the producing microorganism to be a strain of Streptomyces gardneri. The major
      portion of the antibiotic produced remained associated with the mycelial biomass,
      from which it was extracted with polar solvents such as aqueous methanol or
      aqueous acetone. Initial A10255 yields of < 2 micrograms/ml were increased to
      over 300 micrograms/ml in stirred reactors through strain selection, nutritional
      studies, and conversion of the batch fermentation to a fed-batch mode.

PMID- 1399841
TI  - Acaterin, a novel inhibitor of acyl-CoA: cholesterol acyltransferase produced by
      Pseudomonas sp. A92.
AB  - Acaterin, a novel inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT), was
      isolated from a culture broth of Pseudomonas sp. A92 by Diaion HP-20 column
      chromatography, solvent extraction and reverse phase HPLC. Spectroscopic analyses
      of the compound yielded 3-(1-hydroxyoctyl)-5-methyl-2(5H)-furanone as the
      proposed structure. In the presence of oxidized low density lipoprotein, acaterin
      inhibited the synthesis of cholesteryl ester in macrophage J774 by 50% at a
      concentration of 45 microM. Acaterin also inhibited ACAT activity in the rat
      liver microsomes by 50% at a concentration of 120 microM. Kinetic studies
      suggested that inhibition of ACAT by acaterin was noncompetitive with respect to
      oleoyl-CoA.

PMID- 1399843
TI  - Isolation and structure elucidation of new antibiotics related to angolamycin.
AB  - Angolamycin (1) and two novel analogues (2 and 3) were isolated from the culture
      broth of a Streptomyces strain. NMR and MS analysis proved that 2 is the 18
      dihydro-, while 3 is the 18-deoxo-18-dihydro derivative of angolamycin. Full
      experimental assignment of the 1H and the 13C NMR spectra of these compounds was
      obtained from 1D and 2D chemical shift correlation measurements. Compounds 2 and
      3 are less potent antibiotics than angolamycin.

PMID- 1399844
TI  - Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces
      roseiscleroticus. Production, isolation, structure and biological activity.
AB  - Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and
      antitumor antibiotic, sultriecin. It exhibited in vitro antifungal activity and
      potent in vivo antitumor activity against P388 and L1210 leukemias, and B16
      melanoma. Sultriecin is composed of several unique structural units; a conjugated
      triene, an alpha,beta-unsaturated delta-lactone, and a sulfate functionality.

PMID- 1399845
TI  - Kedarcidin, a new chromoprotein antitumor antibiotic. II. Isolation, purification
      and physico-chemical properties.
AB  - Kedarcidin, a new chromoprotein antitumor antibiotic, was isolated from the
      culture broth of a novel actinomycete strain L585-6 (ATCC 53650). The antibiotic
      was recovered from the culture filtrate by adsorption to QAE ion exchanger and
      purified by successive application of gel filtration and ion exchange
      chromatography with Sephadex G-50 and DEAE-Sephadex, respectively. Kedarcidin is
      an acidic complex (pI 3.65) with an apparent molecular weight of 12,400. The
      complex consists of a highly unstable, solvent extractable chromophore and a
      water soluble peptide. The apoprotein is a single chain polypeptide of 114
      residues.

PMID- 1399846
TI  - Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. I.
      Isolation of antibiotic-blocked mutants and their characterization.
AB  - Biosynthetically blocked mutants were obtained from a baumycin-producing
      Streptomyces sp. D788 newly isolated from soil. The first mutant isolated was a
      baumycin-negative but daunorubicin-accumulating mutant with a loss of 4'
      substitution activity, from which all other blocked mutants were successively
      derived. These included a known 11-deoxydaunorubicin-producing mutant and several
      new types of mutants which produced mainly 10-carboxy-13-deoxocarminomycin, 10
      methoxycarbonyl-13-deoxocarminomycin, their 11-deoxy derivatives or a precursor
      aglycone, respectively. In this paper, all the anthracycline components produced
      by the parent strain and its two known blocked mutants, a daunorubicin producer
      and a 11-deoxydaunorubicin producer, are also determined by HPLC and five new
      components are isolated. Cytotoxicities in vitro of all the components against
      L1210 cell culture are also described.

PMID- 1399847
TI  - Vermixocins A and B, two novel metabolites from Penicillium vermiculatum.
AB  - Vermixocins A and B, 3-(1'-hydroxy-3'-methylbutyl)- and 3-(1'-acetoxy-3'
      methylbutyl)-11-hydroxy-4-methoxy-9-methyl-5H,7H- dibenzo[c,f][1,5]dioxocin-5
      one, respectively, were isolated from the mycelium of Penicillium vermiculatum.
      Both metabolites showed cytotoxic effects on lympholeukemia cells P388.

PMID- 1399848
TI  - Enniatin synthetases from different fusaria exhibiting distinct amino acid
      specificities.
AB  - Enniatin synthetases from the cyclodepsipeptide producers Fusarium lateritium and
      Fusarium sambucinum were purified to homogeneity and characterized. Like the
      previously described enniatin synthetase from Fusarium scirpi both enzymes
      consist of a single polypeptide chain and are very similar concerning their Mr
      (250 kdaltons) and reaction mechanism. Limited proteolytic digests show only
      slight differences in their patterns in SDS-gels. Interestingly the synthetases
      differ in their amino acids specificities. The enzyme from the enniatin A
      producer F. sambucinum exhibits a high affinity to the substrate amino acids L
      Leu and L-Ile. In contrast the synthetase from the enniatin B producer F.
      lateritium preferably accepts L-Val, the constituent amino acid of enniatin B.

PMID- 1399849
TI  - Biosynthesis of thiopeptide antibiotic A10255 in stirred reactors using a
      chemically defined medium supplemented with continuous nutrient feeds.
AB  - A10255 is a complex of new thiopeptide antibiotics produced by Streptomyces
      gardneri. When stirred reactors were operated in batch mode using a defined
      medium with a glucose feed, 250 micrograms/ml of A10255 were produced during a
      four-day fermentation cycle. The linear growth phase of S. gardneri was extended
      through seven days by supplementing the defined medium with continuous feeds of
      hydrolyzed casein and methyl caprate. With the supplementary feeds, antibiotic
      biosynthesis paralleled growth during the extended cycle and attained levels of
      1,750 micrograms/ml. Increasing the standard glucose feed rate increased titers
      principally by increasing cell mass. Supplementing the standard glucose feed with
      lipids such as caprylate or caprate, and decyl alcohol, affected cell mass
      minimally but produced higher titers by increasing the specific biosynthesis of
      A10255 per unit of biomass.

PMID- 1399850
TI  - Cloning of aklavinone biosynthesis genes from Streptomyces galilaeus.
AB  - Aklavinone is an aglycone of aclacinomycin A which is an important antitumor
      drug. Genes for the biosynthesis of aklavinone were cloned from Streptomyces
      galilaeus 3AR-33, an aklavinone-producing mutant, by use of the actI and actIII
      polyketide synthase gene probes. Restriction mapping and Southern analysis of the
      DNA cloned in a lambda phage vector established that the DNA represented three
      different regions of the S. galilaeus 3AR-33 genome that contained 3.4, 2.5, and
      4.1 kb BamHI fragments which hybridized with actIII. Of those, only the 3.4 kb
      fragment also hybridized with actI. Complementation experiments with specifically
      blocked mutants confirmed that the cloned 3.4 kb BamHI fragment contains the
      genes required for the early stage of polyketide synthesis in aklavinone
      biosynthesis.

PMID- 1399851
TI  - Immunomodulating properties of prodigiosin 25-C, an antibiotic which
      preferentially suppresses induction of cytotoxic T cells.
AB  - An antibiotic, prodigiosin 25-C, preferentially suppresses cytotoxic T
      lymphocytes (CTL) without affecting antibody production. Here, we investigated
      the effect of prodigiosin 25-C on delayed-type hypersensitivity (DTH), graft
      versus host reaction (GvHR) and allogeneic skin graft rejection. DTH reactions
      were markedly inhibited by ip treatment of the mice with prodigiosin 25-C. Cell
      transfer experiments indicated that prodigiosin 25-C exerted its suppressive
      effect on the late efferent phase rather than on the induction phase of DTH.
      Prodigiosin 25-C suppressed induction of anti-host CTL when GvHR was induced by
      iv inoculating splenocytes of parental C57BL/6 mice to adult unirradiated BDF1
      mice. It had little effect on GvHR-induced splenomegaly observed 2 weeks after
      the inoculation, but significantly delayed the subsidence of splenomegaly as
      revealed 8 weeks later, suggesting that suppression of CTL converts
      immunosuppressive GvHR to immunostimulative one as reported by G. M. Shearer.
      However, reduction of interleukin-2 (IL-2) production and mitogen responses
      induced by GvHR were not rescued by prodigiosin 25-C treatment. Prodigiosin 25-C
      moderately prolonged survival of major histocompatibility (MHC)-mismatched skin
      grafts. Since the mode of action of prodigiosin 25-C is distinct from those of
      cyclosporin A and FK506, these results demonstrate potential usefulness of the
      antibiotic for a supplementary immunosuppressant.

PMID- 1399852
TI  - Enhancement by concanavalin A of the suppressive effect of prodigiosin 25-C on
      proliferation of murine splenocytes.
AB  - Proliferation of concanavalin A (Con A)-activated nylon-wool purified murine
      splenic T cells was increasingly suppressed by prodigiosin 25-C as higher
      concentrations of Con A were used for the activation. Enhancement of suppressive
      effect of prodigiosin 25-C was not observed when T cells were stimulated with
      phytohemagglutinin (PHA), anti-CD3 antibody, or allogeneic splenic adherent
      cells. The suppressive effect of prodigiosin 25-C was enhanced by the addition of
      Con A in various T cell subpopulations as well as in LPS-activated splenic B
      cells. Lectins that recognize mannose residue of biantennary-complex-type sugar
      chains significantly enhanced the suppressive effect of prodigiosin 25-C, whereas
      a lectin that binds to N-acetylglucosamine did not. These results suggest that
      binding of lectins to the mannose residue of biantennary-complex-type sugar
      chains on cell surface of both T and B lymphocytes plays a central role on the
      enhancement of the suppressive effect of prodigiosin 25-C.

PMID- 1399853
TI  - Protorubradirin, an antibiotic containing a C-nitroso-sugar fragment, is the true
      secondary metabolite produced by Streptomyces achromogenes var. rubradiris.
      Rubradirin, described earlier, is its photo-oxidation product.
AB  - In an attempt to improve the isolation of the antibiotic rubradirin from
      fermentations of Streptomyces achromogenes var. rubradiris, the use of
      preparative reversed-phase chromatography was investigated. The product isolated
      was a mixture of rubradirin and a new antibiotic named protorubradirin, of
      extremely similar structure, which is converted into rubradirin on exposure to
      light and air. Methanolysis of protorubradirin in the dark yields an anomeric
      mixture of methyl glycosides of a C-nitroso-sugar, converted photo-oxidatively
      into the methyl rubranitrosides derived from rubradirin. Thus, protorubradirin is
      the C-nitroso-analogue of rubradirin. It is suggested that the same relationship
      between protorubradirin and rubradirin may apply to the anthracycline antibiotics
      viriplanin A and viriplanin D.

PMID- 1399854
TI  - Structural characterization of bacitracin components by Frit-fast atom
      bombardment (FAB) liquid chromatography/mass spectrometry (LC/MS).
AB  - The structural characterization of minor components of bacitracin (BC) complex
      was carried out using a technique of liquid chromatography/mass spectrometry
      (LC/MS). Satisfactory total ion current chromatogram of BC complex and excellent
      mass spectra of many components were given by Frit-fast atom bombardment (FAB)
      LC/MS analytical system, and the structures of 13 minor components could be
      proposed. The 13 minor components were classified into two groups, bacitracin A
      (BC-A) related components and bacitracin F (BC-F) related components depending on
      their common N-terminal moieties. The structures of BC-A related components and
      BC-F related components were the same as those of BC-A and BC-F, respectively,
      except that one to three of isoleucine and leucine residues are replaced by
      valines. The BC-F related components were degradation products of BC-A related
      components through the same degradation process as that of BC-A.

PMID- 1399855
TI  - Cefclidin (E1040), a novel cephalosporin: lack of selection of beta-lactamase
      overproducing mutants in an in vitro pharmacokinetic model system.
AB  - The bactericidal activity of cefclidin (E1040), a new cephalosporin, against a
      clinical strain of Citrobacter freundii was compared with that of ceftazidime in
      a two-compartment in vitro pharmacokinetic model system designed to simulate
      plasma concentrations in humans for 12 hours after intravenous administration of
      a 1 g dose. Both cefclidin and ceftazidime showed rapid bactericidal activity
      against C. freundii. However, during the simulation of ceftazidime treatment,
      regrowth was observed after two hours and a subpopulation emerged which was
      resistant to ceftazidime. Neither regrowth nor the emergence of resistant mutants
      was observed with cefclidin during the 12-hour simulation. The ceftazidime
      resistant mutants constitutively overproduced beta-lactamase at levels which were
      about 500-fold higher than that of the parent wild-type strain. Against this beta
      lactamase overproducing mutant, no bactericidal activity of ceftazidime was
      observed in the in vitro model system, whereas the bactericidal activity of
      cefclidin was observed during the 12-hour period. The emergence of Enterobacter
      cloacae mutants derepressed for beta-lactamase production was also observed with
      ceftazidime but not cefclidin. The affinity of cefclidin for the beta-lactamase
      isolated from these mutants was lower than that of ceftazidime, and the kinetic
      parameters of enzymatic hydrolysis showed that cefclidin was hydrolyzed more
      slowly at a low concentration (0.2 microM) than was ceftazidime. It is suggested
      that the high activity of cefclidin against strains derepressed for beta
      lactamase plays a major role in the absence of emergence of resistant mutants.

PMID- 1399856
TI  - Structure-binding relationship and binding sites of cephalosporins in human serum
      albumin.
AB  - The binding of some cephalosporins to human serum albumin (HSA) was studied by an
      ultrafiltration technique. Changes in C-3 side chain resulted in marked changes
      in the binding to HSA, but changes in C-7 side chain did not. Cephalosporins were
      classified into three groups by C-3 side chain: (i) Cationic side chain with low
      affinity for HSA; (ii) anionic side chain with high affinity for HSA; (iii) non
      ionized side chain, in which binding to HSA was dependent on lipophilicity. These
      findings suggest that electrostatic and hydrophobic forces play a role in the
      binding affinity of cephalosporins for HSA. The binding of cephalosporins with
      high HSA affinity was displaced significantly by warfarin but not by
      phenylbutazone, L-tryptophan, or diazepam. The interaction of the cephalosporins
      with high affinity for HSA with chemically modified HSA was investigated to
      clarify the amino acid residues of HSA involved in the cephalosporin binding
      sites. The binding of the cephalosporins decreased remarkably with the
      modification of the tyrosine residues. These results suggest that the binding
      site of cephalosporins is located in the vicinity of warfarin binding site rather
      than benzodiazepine binding site and that tyrosine residues are involved in the
      cephalosporin binding site.

PMID- 1399857
TI  - Orally active 2-(alkyloxycarbonyl)-2-alkylideneethyl esters of cephalosporins.
AB  - 2-(Alkyloxycarbonyl)-2-alkylideneethyl esters of various aminothiazole-oxyimino
      cephalosporins have been synthesized and studied. They are useful alternatives to
      the currently existing orally active esters. Among the new esters synthesized,
      the 3'-azidomethyl cephem ester Ro 41-3399 (7k) presented an oral bioavailability
      superior to the corresponding pivaloyloxymethyl ester (9) in a rat model and was
      selected as a candidate for further evaluation.

PMID- 1399859
TI  - The new cytotoxic antibiotic cytorhodin X, an unusual anthracyclinone-9 alpha
      glycoside.

PMID- 1399858
TI  - A new immunosuppressive cytochalasin isolated from a Pestalotia sp.

PMID- 1399860
TI  - Microbial production of 4-thiouridine.

PMID- 1399861
TI  - Oxidation of deacetylcephalosporin C by deacetoxycephalosporin
      C/deacetylcephalosporin C synthase.

PMID- 1399862
TI  - Biosynthetic preparation of radioactively labeled erbstatin.

PMID- 1399863
TI  - Travel tips for women.

PMID- 1399864
TI  - Growing up heartsick: the experiences of young women with congenital heart
      disease.
AB  - Young women with congenital heart disease (CHD) now survive to confront issues of
      sexuality, contraception, and pregnancy. Researchers have examined reproductive
      abilities and infant outcomes in these women, but have not addressed quality-of
      life issues. Grounded-theory techniques were used to interview 13 women about the
      experience of growing up with CHD. The core variable identified was "growing up
      heartsick." This variable included manifestations of growing up with heart
      disease, such as feeling different from others, parental overprotectiveness, and
      fears of death. Two other related variables were also found: "growing up female"
      and "living against the body." "Growing up female" was characterized by concerns
      about fertility, contraception, and pregnancy in relation to CHD. Many of the
      participants were uninformed about their heart disease and reproductive matters.
      "Living against the body" was expressed in the women's feelings about their body
      size and their surgical scars. There were overlapping aspects of the categories;
      for example, manifestations of "growing up heartsick" appeared in each of the
      other categories.

PMID- 1399865
TI  - The breast-feeding experience of women with type I diabetes.
AB  - The purpose of this exploratory study was to identify the factors influencing the
      initiation and maintenance of breast-feeding in women with insulin-dependent
      diabetes. The lack of research in this area and the need for in-depth data
      necessitated exploratory methodology. Twenty-two mothers who were insulin
      dependent before pregnancy and who had given birth in the past 2 years were
      interviewed. Diabetes was not a principal factor in the decision to breast-feed
      or bottle-feed for the majority of the women. When diabetes was a factor, women
      were seeking a "normal" childbearing experience, including breast-feeding.
      Although the women did not perceive diabetes as influencing their breast-feeding
      experiences, they did find that maintaining good diabetic control required
      greater effort and flexibility during breast-feeding.

PMID- 1399866
TI  - Sociocultural factors in depression in Asian Indian women.
AB  - Depression is a pervasive illness with a wide distribution and is reported to be
      statistically more prevalent among women. The present study was undertaken to
      seek an understanding of depression in a sample of Asian Indian women. The
      research questions were (a) What sociocultural factors do adult depressed Indian
      women report as influences in the depression, and (b) how do these reported
      factors influence their treatment-seeking behavior? The setting was Madurai,
      India. The purposive, convenience sample comprised 30 Tamil-speaking married or
      widowed Hindu women ranging in age from 26 to 65 who had been diagnosed with
      depression. Tape-recorded interviews were conducted. Content analysis was
      completed on the data. Results indicate that cultural dictation of female role
      and lack of continued financial and emotional support, predominantly from spouses
      and other family members, were influential factors in depression. These along
      with religion and philosophy often influenced the decision to seek health care.

PMID- 1399867
TI  - Attitudes of low-income clinic patients toward menopause.
AB  - The bulk of menopause research has been conducted on samples of middle-class
      White women. In this study, attitudes toward menopause in a sample of 66 low
      income women at a women's clinic were studied using Bowles's (1986) Menopause
      Attitude Scale (MAS) and the attitude segment of Millette's (1981) survey of
      attitudes and knowledge about menopause. The typical participant was a single, 34
      year-old Black woman with a yearly income below $10,000. Research questions
      examined general attitudes toward menopause, and MAS scores of Bowles's middle
      income, White sample were compared with those of the present low-income,
      predominantly Black sample. Results indicated a somewhat positive attitude toward
      menopause in the low-income sample. Although the trend was toward higher scores
      in the low-income group, only the 18- to 25-year-olds in the low-income group had
      significantly higher MAS scores than the corresponding age group in Bowles's
      sample. Nursing implications pertain to teaching and support group leadership.

PMID- 1399868
TI  - Consequences of hysterectomy in the lives of women.
AB  - A longitudinal study of 63 adult, premenopausal women of low socioeconomic status
      who underwent hysterectomies is reported. Face-to-face in-depth interviews with
      the women were conducted on the day before hysterectomy and 4 weeks and 3 months
      after hysterectomy. After the interview, each woman completed the Derogatis
      Sexual Functioning Inventory (Derogatis & Melisaratos, 1979). The Responses to
      Hysterectomy tool was mailed to the women about 2 years after hysterectomy.
      Before their hysterectomies, most of the women had both positive and negative
      feelings about the hysterectomy. By 3 months posthysterectomy, most women had
      fairly positive general and sexual outcomes. However, by 2 years
      posthysterectomy, there were less positive outcomes. Most women reported at least
      sometimes having negative symptoms that they associated with their hysterectomy.
      More research must be conducted to fully understand the experience of
      hysterectomy in women's lives.

PMID- 1399869
TI  - Maternal reactions to fetal sex.
AB  - A descriptive design was used to characterize maternal reactions to the knowledge
      of fetal sex based on sex preference. The sample was 88 females with singleton
      pregnancies who had had an amniocentesis for fetal chromosome studies and met the
      following sample criteria: (a) Fetal karyotype and other studies were normal, (b)
      knowledge of fetal sex was desired, and (c) sex preference had been established.
      Maternal reactions to the knowledge of fetal sex were ascertained through a
      questionnaire I developed and that participants answered in writing. Sample
      characteristics were summarized using descriptive statistics, and the mothers'
      narrative responses were subjected to content analysis. Maternal sex preferences
      were equally split between male and female. However, there were differences in
      the way mothers who attained and mothers who did not attain their preferred fetal
      sex spoke of their fetuses.

PMID- 1399870
TI  - Sex role typology as a function of age among registered nurses.
AB  - The present study was designed to investigate the relationship between sex role
      orientation and age in women working in a traditional occupation. It was
      hypothesized that older working female nurses would be more androgynous in sex
      role orientation than their younger counterparts. Ninety-eight female registered
      nurses ranging in age from 30 to 59 completed the Personal Attributes
      Questionnaire and sociodemographic data. Contrary to prediction, age had no
      significant effect on sex role orientation. It was concluded that (a) no change
      in masculinity/femininity self-descriptions occur over time, (b) only some women
      change, and (c) changes may proceed in different directions in response to shifts
      in role responsibilities or other situational events.

PMID- 1399871
TI  - Content analysis: method, applications, and issues.
AB  - Content analysis research methodology is detailed, its procedures are described,
      some examples of its application are provided, and the controversial issues
      surrounding its use are discussed. Unlike strictly qualitative designs, content
      analysis has external validity as a goal. Because of its focus on human
      communication, content analysis offers practical applicability, promise, and
      relevance for research involving the practice and education of nurses and other
      helping professionals.

PMID- 1399872
TI  - George Colvin Humphrey, 1875-1947: a brief biography.

PMID- 1399873
TI  - Prediction of fertility from calfhood traits of Angus and Simmental heifers.
AB  - The objectives of this study were to quantify the relationships between traits
      observed before the first breeding season and fertility of 946 Angus and 351
      Simmental heifers and to use those traits to develop prediction equations for
      heifer fertility. Logistic regression methodology was used. Traits investigated
      were Julian birth date, age of the heifer's dam, birth weight, actual weaning and
      yearling weights, weaning and yearling weight ratios, 205-d weight, 365-d weight,
      and birth-weaning, weaning-yearling, and birth-yearling ADG and relative growth
      rate (RGR). In both breeds heifers that were younger at the start of the breeding
      season were less likely to conceive, but this effect was more important for Angus
      (logistic regression coefficient, b = -.032; P less than .01) than for Simmentals
      (b = -.015; P = .06). Weaning weight ratio was positively associated with heifer
      fertility (b = .025; P = .01 and b = .028, P = .04, respectively, for Angus and
      Simmental), whereas actual weaning weight was related curvilinearly to fertility
      of Angus heifers. The likelihood of conception was highest for Angus heifers
      weighing greater than or equal to 240 kg at weaning. The only postweaning trait
      associated with heifer fertility was weaning-yearling RGR. The likelihood of
      conception was highest for Angus heifers growing between .15 and .30% per day (P
      = .01), whereas fertility increased continuously (P = .04) for Simmental heifers
      as weaning-yearling RGR decreased. The maximum variations in fertility explained
      by models including all possible explanatory variables were 11.5 and 9.2% for
      Angus and Simmental, respectively. Results suggested that growth-related traits
      were relatively more important as a predictor of fertility for Simmental heifers
      and that age at the start of the breeding season was more important for Angus
      heifers. The combination of Julian birth date and weaning-yearling RGR produced
      the best models to predict heifer fertility for both breeds.

PMID- 1399874
TI  - Reproductive response of yearling beef heifers to a melengestrol acetate
      prostaglandin F2 alpha estrus synchronization system.
AB  - A study was designed to evaluate estrus response and fertility after treatment
      with melengestrol acetate (MGA) and prostaglandin F2 alpha (PGF2 alpha) in
      yearling beef heifers. Three hundred four heifers at three locations were
      allotted to one of two treatments: Treatment 1 served as a nonsynchronized
      control (CON); and heifers in Treatment 2 received .5 mg of MGA.animal-1.d-1 for
      14 d and 25 mg of prostaglandin F2 alpha (PGF2 alpha) 17 d after MGA (MGA-PGF).
      Heifers in CON and MGA-PGF groups were artificially inseminated 12 h after
      observed estrus for 21 and 6 d after PGF2 alpha, respectively. Blood samples were
      collected from each heifer 10 d before and on the day MGA feeding began and 10 d
      before and on the day PGF2 alpha was administered. Heifers with concentrations of
      serum progesterone greater than 1 ng/mL on either date before administration of
      MGA or PGF2 alpha were considered pubertal. More (P = .02) prepubertal heifers
      that received MGA attained puberty by initiation of breeding than did CON heifers
      (72 vs 45%, respectively). The proportion of heifers that displayed estrus within
      6 d after PGF2 alpha was greater (P less than .001) for MGA-PGF than for CON
      heifers (77 vs 25%, respectively) but was also influenced by location (P = .03).
      Conception rate at first service for MGA-PGF heifers that attained puberty during
      MGA feeding and before PGF2 alpha was not different (P = .50) from that of CON
      that attained puberty during the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399875
TI  - Accelerated lambing using exogenous progesterone and the ram effect.
AB  - An experiment was conducted to determine whether controlled internal drug release
      devices-type G (CIDR-G) could be used in conjunction with the ram effect to
      advance the breeding season and lambing and thereafter could be reapplied to
      stimulate breeding of ewes to produce a second lambing in late summer. Finn
      crossbred and Columbia ewes were treated with CIDR-G from July 6 to 18. Rams,
      which had been isolated from ewes, were joined with the flock upon CIDR-G
      removal. All 59 CIDR-G-treated ewes exhibited estrus, and 55 lambed from breeding
      within a 30-d period after CIDR-G withdrawal. Eighteen of 19 contemporary control
      ewes (no CIDR-G) were bred, and 16 lambed. Ewes that had lambed from the CIDR-G
      and control groups were retreated as before, with CIDR_G inserted March 1 and
      withdrawn March 13, concomitant with sudden exposure to rams. Of 55 CIDR-G
      treated sheep, 53 were bred and 45 lambed. All 16 control ewes were bred and
      lambed. A second experiment was conducted to determine whether treatment with
      CIDR-G and the ram effect was effective in mid-spring. The CIDR-G were applied
      for 12 d and removed on May 1 or 6 from Finn crossbred, Columbia, and Polypay
      ewes. Rams were introduced upon CIDR-G withdrawal. Of 59 CIDR-G-treated ewes, 58
      exhibited estrus and 45 lambed. Twenty-three of 30 contemporary control ewes were
      bred, and 20 lambed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399876
TI  - Lactation performance of sows injected with growth hormone-releasing factor
      during gestation and(or) lactation.
AB  - Fifty-two Yorkshire x Landrace gilts were equally allotted to four treatments: 1)
      controls, saline injections (CTL); 2) injections of 12 mg of growth hormone
      releasing factor (GRF) (1-29)NH2 thrice daily (0700, 1500, and 2300) from d 100
      of gestation until parturition (GEST); 3) injections of GRF thrice daily from d 3
      to 29 of lactation (LACT); and 4) injections of GRF thrice daily during gestation
      (d 100 to parturition) and lactation (d 3 to 29) (GEST-LACT). Within 48 h of
      birth, litters were standardized to 9 +/- 1 pigs. Weights of the pigs were
      recorded weekly from birth (less than 24 h) until weaning (d 30) and on d 42 and
      56. Weights of gilts at mating, d 110 of gestation, 1 d postfarrowing, and at
      weaning also were recorded. On d 24 of lactation, milk yield was estimated by the
      weigh-suckle-weigh method, and a representative milk sample was obtained the next
      day. Jugular vein cannulas were inserted into six sows per treatment on d 26, and
      a 6-h blood profile (sampling every 20 min from 0600 to 1200) was obtained on d
      29. Daily feed consumption of sows was recorded throughout the study. Weights of
      the pigs at any one time or survival until weaning were not affected by
      treatments (P greater than .1). Sows injected with GRF during GEST (P = .05)
      and(or) LACT (P less than .01) were lighter than CTL sows at weaning; in
      addition, sows treated during lactation had less backfat (P less than
      .01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399877
TI  - Management systems for Holstein steers that utilize alfalfa silage and improve
      carcass value.
AB  - Two trials were conducted to evaluate the effect of two-phase feeding systems
      using alfalfa silage or pasture on the performance and carcass characteristics of
      Holstein steers. During the growing phase (98 d) of Trial 1, steers received
      alfalfa silage at either 40, 22, or 7% of the DMI. During the growing phase of
      Trial 2, steers received alfalfa silage at either 39 or 8% of their DMI (140 d)
      or grazed an orchardgrass/ryegrass pasture (175 d). During the finishing phase,
      all steers received a 90% concentrate diet until they reached a small degree of
      marbling at the 12th rib as predicted by ultrasonic attenuation. In Trial 1, one
      half were initially implanted with zeranol and reimplanted with trenbolone
      acetate and estradiol (TBA+E) after 98 d. In Trial 2, one-half were implanted
      twice with TBA+E at a 120-d interval. Trial 1 average daily gains (kilograms) for
      the 40, 22, and 7% alfalfa silage treatments were 1.14, 1.25, and 1.38 in Period
      1 (all different from each other at P less than .05); 1.31, 1.34, and 1.19 in
      Period 2; and 1.25, 1.25, and 1.26 overall. Trial 2 average daily gains
      (kilograms) for the 39, 8, and pasture treatments were 1.50, 1.71, and .92 for
      Period 1 (all different from each other at P less than .05); .93, .75, 1.11 for
      Period 2 (all different from each other at P less than .05); and 1.16, 1.17, and
      1.03 overall (pasture different at P less than .05). No consistent effects of
      diet or implant on carcass characteristics were observed.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1399878
TI  - Predicting the profitability of alfalfa silage and pasture feeding systems for
      Holstein steers.
AB  - Data from two research trials were used as inputs to a model to project the
      return to capital of two-phase alfalfa silage and pasture feeding systems for
      Holstein steers. This approach presents a methodology for applying research data
      over widely varying conditions. Cattle received a 40% (High = H), 22% (Medium =
      M), or 8% (Low = L) alfalfa silage diet or grazed an orchardgrass/ryegrass
      pasture (Pasture = P) during Period 1. During Period 2, cattle consumed a 90%
      concentrate diet until ultrasonic attenuation predicted that the longissimus
      muscle contained a small degree of marbling. All systems produced similar carcass
      grades, so profitability differences resulted from relationships between feed
      requirements, cost of feed, and cost of time. Cattle grazed on pasture yielded a
      higher return to capital during Period 1 and over the entire feeding system.
      Among the other systems, L returned more to capital during Period 1, but over the
      entire feeding system additional silage returned more when silage cost was less
      than $32 per 1.02 t (as fed). Above this cost, the continuous 90% concentrate
      diet yielded a higher return. Cattle implanted with trenbolone acetate and
      estradiol returned $60 in Trial 1 and $86 in Trial 2 more per animal than did
      unimplanted steers.

PMID- 1399879
TI  - Forage availability x heifer phenotype interactions for Brahman-Hereford F1
      yearling heifers grazing humid pasture and semiarid rangeland.
AB  - Yearling heifer growth data were obtained during 4 yr for 524 heifers allotted to
      either humid bermuda grass pastures (Overton) or semiarid rangeland (Uvalde).
      Each year, heifers were allotted on April 15 to four forage availability levels
      (400 to 2,800 kg of DM per 100 kg of BW at Uvalde and 80 to 260 kg of DM per 100
      kg of BW at Overton) maintained by varying the stocking rate monthly until mid
      October of each year. Forage availability and yearling heifer characteristics
      (weight, condition score, and height at hooks, taken on April 15) were treated as
      continuous variables in regression analyses. Final heifer weight, height, and
      condition responses to increased forage allowance were related to yearling
      phenotypes differently for the two locations. Generally, at Overton, forage
      availability influenced final characteristics to a greater extent than did
      yearling variables, whereas the trend was the opposite at Uvalde. At Uvalde, the
      yearling characteristic that had the largest effect on performance was height at
      hooks. Yearlings with large frames benefited from increased forage allowance by
      accumulating body fat at a faster rate than those with small frames. In contrast,
      at Overton, the yearling characteristic that had the largest effect on
      performance was condition. Fat heifers responded to increased forage availability
      to gain even greater advantages in fatness at the expense of potential growth in
      height and, thus, achieved early maturation. Yearling phenotypes were more
      broadly adapted to arrays of forage availability for humid, improved pastures
      than for semiarid rangeland.

PMID- 1399880
TI  - Effects of growth curve parameters on cow efficiency.
AB  - Weight-age data from 50 Retinta beef cows from 8 to 97 mo of age located in
      southwestern Spain were fitted to von Bertalanffy, Brody, and Richards functions
      to determine the relationship between growth curve parameters and cow efficiency.
      Only cows having at least 31 weights were included in the analysis. Von
      Bertalanffy, Brody, and Richards functions were fitted to weights of each cow.
      Relevant parameters of the three functions are A and K, associated with the
      asymptotic mature weight and rate of maturing, respectively. Criteria for
      comparisons among the three functions were computing difficulty, goodness of fit,
      and lack of bias of A. Productivity indicators were number of calves weaned
      during the first five calving seasons (NC), average birth weight (BWT), average
      weaning weight (WW), and average weaning weight per cow per year (WWY). The von
      Bertalanffy function was selected as the most appropriate. Least squares means
      for A and K were 650 +/- 8.17 kg and .038 +/- .001 mo-1, respectively. The values
      of NC, BWT, WW, and WWY were 4.0 +/- .11 calves, 38.2 +/- .4 kg, 218 +/- 5 kg,
      and 172 +/- 5 kg, respectively. Regression analysis for A indicated a decrease in
      NC when mature weight increased (P less than .05). There was a nonsignificant
      trend for heavier cows (higher A) to have calves with heavier BWT or WW. The
      value of WWY increased (P less than .05) with increased maturing rate (K) of
      cows. No significant associations were found between K and BWT or WW.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1399881
TI  - Classical and mixed-model analysis of an index selection experiment for fecundity
      in Drosophila melanogaster.
AB  - A comparison of three family indices to increase number of pupas from 3-d lay in
      Drosophila melanogaster is reported. The three indices were Id, based exclusively
      on dam's information; Ihd, based additionally on dam's full-sibs' and half-sibs'
      information; and Ihs, which also included the sire's full-sibs' and half-sibs'
      records. Three lines, D, HD, and HS, were selected, each according to one of the
      three indices: Id, Ihd, or Ihs. Each line consisted of 10 sires and 60 dams. Each
      dam contributed one male offspring and three female offspring. Seven generations
      of selection were performed in a two-replicate experiment. The expected advance
      of Ihs and Ihd over Id in the seventh generation was .38 and .15 phenotypic
      standard deviations, respectively. The experiment was analyzed in terms of both
      classical ordinary least squares (OLS) and mixed-model methodology (MMM). The
      phenotypic trends in the first replicate were 4.06 +/- 1.74, 1.42 +/- 1.76, and
      .26 +/- 1.94 pupas per generation for Lines D, HD, and HS, respectively, and in
      the second replicate 8.52 +/- 2.40, 6.16 +/- 3.21, and 4.21 +/- 2.60,
      respectively. The genetic trends in the first replicate were 2.18 +/- .61, 1.08
      +/- .67, and .24 +/- .68 pupas per generation and, in the second replicate, 2.51
      +/- .60, .16 +/- .61, and .05 +/- .64 for Lines D, HD, and HS, respectively.
      Despite theoretical expectations, the Id index was consistently better than the
      more complex indices. Several explanations for these results are possible: 1)
      smaller than expected selection differential, 2) inbreeding depression, and 3)
      incorrect heritability used to construct the indices.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1399882
TI  - Performance of crosses among Hereford, Angus, and Simmental cattle with different
      levels of Simmental breeding: VI. Maternal heterosis of 3- to 8-year-old dams and
      the dominance model.
AB  - Data from Hereford, 25% Simmental-75% Hereford, 50% Simmental-50% Hereford, and
      75% Simmental-25% Hereford dams were used to estimate maternal heterosis and
      level of agreement with the dominance model. Cows were located at the Northern
      Agricultural Research Center near Havre, MT and were managed consistent with
      practices for western range environments. Sample halves of dam breed groups were
      bred to Charolais and Tarentaise sires to produce calves at 3 to 8 yr of age.
      There were 766 exposures to breeding that resulted in 581 calves. Breed group
      means for most traits supported the dominance model. Maternal heterosis was
      estimated by regression techniques for 22 cow and calf traits. Maternal heterosis
      was not significant for day of conception, number of services, gestation length,
      or calving difficulty. Estimates of maternal heterosis for calf growth traits
      ranged from .7% for weaning height to 5.2% for weaning weight and 7.5% for
      weaning condition score. Calf weight per unit of cow weight at weaning showed
      significant maternal heterosis (7.1%). Higher levels of maternal heterosis were
      exhibited for milk production (8.2 to 11.1%) and the negative, but
      nonsignificant, estimate of maternal heterosis for early minus late milk
      production suggested more persistent lactation for crossbred cows. Maternal
      heterosis was 11.5% for proportion of dams that calved and 10.4% for proportion
      of dams that weaned calves. Calf weaning weight per cow exposed to breeding, a
      characteristic combining calf growth and dam reproduction, exhibited 17.9%
      maternal heterosis.

PMID- 1399883
TI  - Additive and nonadditive differences in postweaning growth and carcass
      characteristics of Devon, Hereford, and reciprocal-cross steers.
AB  - Postweaning growth and carcass characters of 110 steers from a complete two-breed
      diallel of the Devon and Hereford breeds were examined under two environments.
      Additive and nonadditive effects were estimated using linear contrasts for
      several growth and carcass traits. Steers from each of the four breed groups were
      grown postweaning to slaughter in high- and low-nutrition environments. Weights
      were recorded every 2 mo. At slaughter, hot carcass weight, longissimus muscle
      area, kidney and channel fat, and subcutaneous fat at nine sites were measured.
      Heterosis for postweaning growth rate was 3.9% (P less than .01) and for
      slaughter weight 5.0% (P less than .01). Within the low-nutrition environment
      during periods of slow and fast growth, the Devons and Herefords performed
      differently. The growth rate of the steers differed in the two environments;
      however, heterosis for slaughter weight was of the same magnitude in both
      environments. No differences existed between the straightbreds or between the
      reciprocal crosses for slaughter weight. Crossbred carcasses were 7.4% heavier (P
      less than .01) than the straightbred carcasses; however, this effect was removed
      after adjustment for differences in slaughter weight. Heterosis for longissimus
      muscle area and carcass fatness were not significant after adjusting for carcass
      weight. Additive differences occurred for carcass traits. Devon carcasses had
      more kidney and channel fat (P less than .05) at a constant hot carcass weight
      and differences occurred in the partitioning of fat within the subcutaneous
      depot. No significant maternal effects were observed for the carcass traits
      measured. Crossbreeding increased carcass weight without altering composition,
      and relative performance was not affected by the diverse environments.

PMID- 1399884
TI  - Detection of linkage between genetic markers and genes that affect growth and
      carcass traits in pigs.
AB  - Segregation of paternal marker alleles in the progeny of a single boar was used
      to estimate linkage between the marker genes and associations of these genes with
      quantitative trait loci (QTL). The sire was heterozygous at four polymorphic
      marker loci, haptoglobin (HP), glucosephosphate isomerase (GPI), phosphogluconate
      dehydrogenase (PGD), and esterase D (ESD), and sired 30 litters during an 8-mo
      period. Glucosephosphate isomerase and PGD were linked (theta = .09; P less than
      .005). The phase of these two loci in the sire was determined to be GPI A-PGD B,
      GPI B - PGD A. NO other linkages were detected. Growth (135 less than or equal to
      n less than or equal to 172) and carcass data (70 less than or equal to n less
      than or equal to 80) were analyzed assuming a fixed linear model. Least squares
      means were compared for differences in growth and carcass traits between pigs
      that inherited alternative paternal marker alleles. Pigs that inherited the GPI A
      allele from the sire had a 22-g higher daily live weight gain postweaning and
      reached 103 kg live weight in 2.6 fewer days than did pigs that inherited the GPI
      B allele (P less than .05), indicative of the presence of gene(s) that affect
      rate of gain linked to the GPI locus. Pigs that inherited the PGD B allele had a
      .14 unit higher score for muscle firmness (score ranged from 1 to 3 units) than
      pigs that inherited the PGD A allele (P less than .05). Pigs that inherited the
      HP 3 allele had a .06-kg higher weaning weight and a .11 lower ham muscle mass
      score than did pigs that inherited the HP 2 allele from the sire (P less than
      .05). No associations with quantitative traits were detected for ESD.

PMID- 1399886
TI  - Sexual performance of rams in serving capacity tests predicts success in pen
      breeding.
AB  - The purpose of this study was to determine the extent to which sexual performance
      (serving capacity) tests can be used to predict the sexual behavior and
      reproductive success of rams in the context of pen mating. Standard serving
      capacity tests were used to select four low (LP) and four high-performing (HP)
      rams from a population of 94 yearling males. Each selected ram was then exposed
      to approximately 30 estrus-synchronized ewes for a 9-d period. Ejaculations
      observed and mounting marks left on ewes confirmed the greater (P less than .001)
      sexual activity of the HP rams in the field. In addition, ewes exposed to HP rams
      had a higher lambing percentage, more lambs born, and more live lambs born per
      ewe. Ram classification was not related (P greater than .60) to the number of
      lambs born per ewe lambing (prolificacy). It was concluded that serving capacity
      tests, properly conducted, can be used to predict ram mating performance and thus
      aid in establishing more efficient ram-to-ewe stocking rates.

PMID- 1399885
TI  - Correlated responses in reproductive and carcass traits to selection for 200-day
      weight in Duroc swine.
AB  - Correlated responses in reproductive and carcass traits from a line of Duroc pigs
      selected for increased 200-d weight along with a randomly selected control line
      were studied in 189 litters (116 select, 73 control) and 191 pigs (106 select, 85
      control), respectively. Reproductive and maternal traits studied included litter
      sizes born, born alive, and alive at 21 d and litter weight at birth and at 21 d.
      Carcass traits studied were carcass length, longissimus muscle area, average
      backfat thickness, 10th rib backfat thickness, specific gravity, weights of
      closely trimmed ham, loin, and shoulder, belly weight, subjective scoring of the
      longissimus muscle for color and marbling, estimated percentage of muscle and
      lean gain per day. Total weighted cumulative selection differential for 200-d
      weight was 81.7 kg. The realized heritability for 200-d weight was .18 +/- .08,
      and the change in 200-d weight was 2.5 +/- 1.2 kg per generation. The regression
      coefficient of litter size born on generation was -.29 +/- .12 (P less than .10)
      pigs per generation. None of the other regression coefficients for the
      reproductive traits differed from zero. Average backfat thickness, 10th rib
      backfat thickness, and belly weight increased by .093 +/- .016 cm, .122 +/- .029
      cm, and .089 +/- .040 kg, respectively, per generation. Specific gravity, ham
      weight, shoulder weight, color score, and percentage of muscle decreased -.00086
      +/- .00024, -.165 +/- .013 kg, -.104 +/- .011 kg, -.035 +/- .015 points, and -.47
      +/- .12%, respectively, per generation in response to the selection.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1399887
TI  - Relative importance of vision and olfaction for detection of estrus by bulls.
AB  - The objective of this experiment was to determine the relative importance of
      olfaction and visual observation of heifer mounting behavior to the detection of
      estrus by bulls. An observation pen was designed to allow the evaluation of the
      preference of five sexually experienced bulls under three sets of stimuli. The
      observation pen was 4 m x 17 m with a smaller enclosure (2 m x 4 m) at each end
      that housed either a pair of heifers in diestrus (D), a pair of heifers in estrus
      that were allowed to mount one another (EM), or a pair of heifers in estrus that
      were separated by an aluminum panel to prevent mounting behavior (E). The
      preference of bulls was determined between EM heifers compared to D heifers, EM
      heifers compared to E heifers, and E heifers compared to D heifers. Each bull was
      individually allowed 5 min inside the observation pen to demonstrate its
      preference. Preference was defined as the total time that bulls spent within 2.5
      m of either pair of heifers. Each bull was subjected to 10 observation periods of
      each set of stimuli during a 4-mo period. Bulls preferred to be near EM heifers
      compared with either E or D heifers (P less than .05). However, the bulls
      demonstrated no preference (P greater than .05) for E heifers compared with D
      heifers. These data indicate that when physical contact is denied, bulls use
      visual observation of female homosexual behavior as the primary indicator of
      estrus and that olfaction alone provides insufficient stimuli for bulls to
      indicate preference toward heifers in estrus compared with heifers in diestrus.

PMID- 1399888
TI  - Effect of a hot environment on performance, carcass characteristics, and blood
      hormones and metabolites of pigs treated with porcine somatotropin.
AB  - A study was conducted to compare the effects of a single 100-mg recombinant
      porcine somatotropin (rpST) implant on performance, carcass characteristics, and
      blood hormones and metabolites of 40 finishing pigs exposed to either a
      thermoneutral (TN; 18 to 21 degrees C) or hot environment (H; 27 to 35 degrees C)
      for 28 or 35 d. Pigs in H gained at a slower rate (P less than .01) than pigs in
      TN. Control and rpST-treated pigs gained at similar rates in respective
      environments. The rpST-treated pigs consumed 13% less feed (P less than .01) than
      the control pigs in both environments, and pigs in H consumed 19% less feed (P
      less than .01) than pigs in TN. Feed efficiency for rpST-treated pigs was 15%
      better (P less than .01) than that for control pigs; environment had no effect on
      feed efficiency. When slaughtered, pigs treated with rpST had less (P less than
      .01) leaf fat and less (P less than .01) 10th rib backfat than control pigs. Pigs
      in H had a lower (P less than .01) final BW and less leaf fat and backfat than
      pigs in TN. The rpST and H had various effects on blood hormones and metabolites.
      The results demonstrated that the benefits of this form of rpST treatment
      achieved under TN were also achieved in H with no interactions between the
      hormone and environment.

PMID- 1399889
TI  - Assessment of factors regulating serum growth hormone binding protein in pigs.
AB  - These studies were conducted to examine the influence of several variables on the
      growth hormone binding protein (GHBP) activity in serum of pigs. Continuous long
      term porcine somatotropin (pST) injections (daily for 6 to 7 wk) increased GHBP
      activity (P less than .05). However, periodic short-term pST injections (daily,
      every 2nd d, or every 4th d for 2 wk) did not cause a significant change in GHBP
      levels (P greater than .40). Although fasting seems to reduce liver GH receptors,
      no difference was observed between fed animals and animals fasted for 5 d (P
      greater than .30). Between 0 and 6 mo of age, boar and gilt serum GHBP activity
      were not significantly different from each other but increased with age in both
      sexes (P less than .0001). There was no significant correlation between serum
      GHBP and BW at 6 mo of age in this study (P greater than .30). In pregnant sows,
      GHBP concentrations were highest at the beginning (d 72) of the third trimester
      (P less than .05). Growth hormone receptor activity reported by other researchers
      and GHBP activity in this study seem to vary similarly except during fasting,
      which may indicate alternate regulation of either the GHBP or the GH receptor.

PMID- 1399890
TI  - Influence of dietary palm oil supplementation on serum lipid metabolites, carcass
      characteristics, and lipid composition of carcass tissues of growing ram and ewe
      lambs.
AB  - The objective of this research was to determine the influence of dietary palm oil
      supplementation on carcass characteristics and lipid composition of tissues from
      growing lambs. Twenty-eight Suffolk x Hampshire lambs were weaned at 60 d of age
      (average 36 kg BW) and assigned to a 2 x 2 factorial arrangement consisting of
      diet (control [NPO] or 10.6% added dietary palm oil [PO]) and sex (ram vs ewe).
      The NPO diet (77% forage and 23% concentrate) contained 11.2% CP and 2.66 Mcal of
      ME/kg. Palm oil replaced molasses in the PO diet. Lambs were individually given
      ad libitum access to feed for 60 d to a final BW average of 50.1 kg. Lipid
      composition of the longissimus muscle and corresponding subcutaneous (s.c.)
      adipose tissue was determined by gas-liquid chromatography (GLC). Lambs fed PO
      were fatter (P less than .01) than lambs fed NPO (.77 vs .56 cm, s.c. fat). Diet
      had no effect on cholesterol content of lean tissue; however, feeding PO
      increased the saturated fatty acids of lean tissue. The s.c. fat from lambs fed
      PO had less (P less than .01) cholesterol (64.79 vs 89.67 mg/100 g) and more
      saturated fatty acids than that from lambs fed NPO. Ewes were fatter (P less than
      .01) than rams, yet they had less cholesterol content in the s.c. adipose tissue
      (68.71 vs 85.74 mg/100 g). High amounts of dietary palm oil fed to growing lambs
      caused changes in fatty acid deposition and cholesterol metabolism and may be a
      useful investigative tool to study lipid metabolism in growing
      ruminants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399891
TI  - Effects of implanting ram and wether lambs with zeranol at birth and weaning on
      palatability and muscle collagen characteristics.
AB  - Thirty-five zeranol-implanted (I) and nonimplanted (NI) ram and wether lambs
      representing four treatments (implanted rams [IR], nonimplanted rams [NIR],
      implanted wethers [IW], and nonimplanted wethers [NIW]) were evaluated for meat
      palatability and muscle collagen characteristics. Rib (longissimus muscle, LM)
      chops from I lambs were juicier (P less than .05) than rib chops from NI lambs.
      Chops from IR lambs had more (P less than .05) detectable connective tissue and
      lower myofibrillar and overall tenderness scores than chops from NIR, IW, or NIW
      lambs. Warner-Bratzler shear (WBS) values tended to be higher (P = .06) for LM
      chops from rams than for those from wethers, but WBS values for Biceps femoris
      (BF) chops were similar (P greater than .05) for rams and wethers. Implanting did
      not affect (P greater than .05) WBS values. Rams had more (P less than .05) LM
      heat-labile (soluble, SC), nonheat-labile (insoluble, IC), and total collagen
      (TC) and a higher (P less than .05) percentage of SC (SC/TC) than did wethers.
      Soluble collagen, TC, and percentage of SC for the BF were higher (P less than
      .05) and IC tended (P = .09) to be higher in chops from rams than in those from
      wethers. Implanting did not affect (P greater than .05) collagen amount or
      solubility. Serum nonprotein hydroxyproline (NPHP) was higher (P less than .05)
      in rams than in wethers throughout the feeding period and tended (P = .05) to be
      higher at slaughter. Implanting did not affect (P greater than .05) serum
      NPHP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399892
TI  - Ultrasonic prediction of carcass merit in beef cattle: evaluation of technician
      effects on ultrasonic estimates of carcass fat thickness and longissimus muscle
      area.
AB  - The objective of this study was to determine technician effects of live animal
      ultrasonic estimates of fat thickness (FTU) and longissimus muscle area (LMAU).
      Steers (n = 36) representing four breed-types (Brown Swiss, Average Zebu-cross
      Mexican, Corriente Mexican, and typical British crossbred) of commercial
      slaughter cattle were isonified to estimate accuracy and repeatability of fat
      thickness (FT) and longissimus muscle area (LMA) measurements by two experienced
      technicians. Repeated measures of FTU and LMAU were taken by technicians on two
      consecutive days with an Aloka 500V ultrasound unit equipped with a 3.5-MHz, 172
      mm scanning width, linear-array transducer. Ultrasonic estimates of fat thickness
      and LMAU were taken at the 12th and 13th rib interface 48 h before slaughter;
      carcass fat thickness (FTC) and longissimus muscle area (LMAC) were measured 48 h
      postmortem. Means for FTU, FTC, LMAU, and LMAC were .91 +/- .36 cm, .82 +/- .40
      cm, 70.7 +/- 9.43 cm2, and 72.4 +/- 8.9 cm2, respectively. Ultrasound and carcass
      measures of FT and LMA were different (P less than .01) among breed-types but
      were not different (P greater than .10) between technicians or for technician x
      breed-type interactions. Pooled simple correlation coefficients (P less than .01)
      were .87 and .86 between FTU and FTC and .76 and .82 between LMAU and LMAC for
      Technicians 1 and 2, respectively. Repeatabilities estimated by intraclass
      correlation methods were .91 +/- .03 and .81 +/- .06 for images repeated over 2 d
      and .95 +/- .02 and .83 +/- .05 for images repeated by two technicians for FT and
      LMA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399893
TI  - Relationship between blood hemoglobin, plasma and tissue iron, muscle heme
      pigment, and carcass color of veal.
AB  - In 41 veal calves divided into three groups and fed different levels of dietary
      iron, blood hemoglobin, plasma iron, liver, spleen, and muscle iron, muscle heme
      pigment, and carcass muscle color at slaughter were studied. At 45 min
      postmortem, total carcass color was visually evaluated in the 41 carcasses. In
      different muscles of the carcasses the color was measured instrumentally using an
      invasive color measurement method at 45 min postmortem (MCDI score) and a surface
      color measurement method at 20 h postmortem (Minolta L*, a*, b*, and Chroma
      scores). Among the three groups, differences (P less than .05) in muscle iron
      concentrations, muscle heme pigment concentrations, and Minolta a*, b*, and
      Chroma scores were found. Most striking were the differences in mean iron
      concentrations in the longissimus thoracis muscles between Groups A (29
      micrograms/g DM) and B (44 micrograms/g DM) and in the semimembranosus muscles
      between Groups A (31 micrograms/g DM) and C (45 micrograms/g DM). The
      correlations found between Minolta L*, a*, or Chroma score and the iron and heme
      pigment concentrations in the semimembranosus muscles were high in comparison
      with those found in the longissimus thoracis and rectus abdominis muscles.
      Compared with the plasma iron concentration, the blood hemoglobin concentration
      showed higher correlations with muscle iron and muscle heme pigment
      concentrations. It can be concluded that different iron concentrations in the
      milk replacer during the first 7 wk of fattening influence, to some extent,
      muscle iron and muscle heme pigment at slaughter. However, these differences were
      not measurable in the overall visual color evaluation of the carcass surface
      muscles.

PMID- 1399894
TI  - The effect of postexsanguination infusion of beef on composition, tenderness, and
      functional properties.
AB  - Ninety culled dairy cows were used in this study and were paired by weight and
      conformation similarity. Forty-five cows were arterially infused immediately
      after bleeding with 10% volume by weight of a solution composed of dextrose
      (.23%), glycerin (.21%), a phosphate blend (.14%) and maltose (.1%). The
      remaining cows (45) served as controls. In infused carcasses, some quantity of
      solution retained was in the following order: supraspinatus, chuck greater than
      longissimus, loin greater than semitendinosus, round muscles. Accordingly,
      percentage of protein, ether-extractable fat, and protein fat-free amounts were
      lowered (P less than .05) and percentage of moisture and moisture protein ratio
      were raised (P less than .05) in the supraspinatus muscle. Tenderness (P less
      than .01) and protein extractability (P less than .15) were improved. No
      difference was observed in water-holding capacity between infused and control
      carcasses. Percentages of moisture fat-free (r = .85) and protein fat-free (r = 
      .97) were highly correlated to moisture-protein ratio. Moisture percentage of the
      fat-free tissue was shown to be a more consistent indicator of added moisture in
      infused whole carcasses compared with moisture:protein ratio and percentage of
      protein fat-free. Very low correlations were observed between tenderness,
      percentage of moisture, percentage of water-holding capacity, and ether
      extractable fat. The economics of the infusion process to the beef industry is
      discussed.

PMID- 1399895
TI  - The effect of alkaloids and seed extracts of endophyte-infected tall fescue on
      prolactin secretion in an in vitro rat pituitary perfusion system.
AB  - The objective of this research was to measure the effects of endophyte-infected
      tall fescue seed extract and various alkaloids associated with the endophyte on
      in vitro prolactin secretion by rat hemipituitaries. Rat anterior pituitaries
      (AP) were dissected into halves and placed in temperature-controlled culture
      chambers (37 degrees C). The tissue was perfused with culture media at a flow
      rate of 12 mL/h. After perfusion for at least 90 min with control media, AP
      halves were exposed to their respective treatments for 15 min before they were
      returned to the control media. The treatments for Exp. 1 were .01 micrograms of
      alpha-ergocryptine/mL of culture medium, .01 microgram of ergonovine/mL of
      culture medium, .01 gram-equivalents of endophyte-infected tall fescue seed/mL of
      culture medium, and .01 gram-equivalents of endophyte free tall fescue seed/mL of
      culture medium. Treatments for Exp. 2 consisted of 10(-4), 10(-6), and 10(-8) M
      concentrations of perloline, N-formyl loline, N-acetyl loline, N-methyl loline,
      and alpha-ergocryptine. alpha-Ergocryptine suppressed (P less than .10) prolactin
      secretion in both experiments. Ergonovine and perloline both stimulated (P less
      than .10) prolactin secretion. The loline alkaloids (N-formyl loline, N-acetyl
      loline, N-methyl loline) had no effect on prolactin secretion. The endophyte
      infected seed extract treatment suppressed (P less than .10) prolactin secretion.
      The endophyte-free seed extract treatment had no effect on prolactin secretion.
      In Exp. 2, prolactin secretion from AP responded to alpha-ergocryptine treatment
      in a dose-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399896
TI  - Release of luteinizing hormone after administration of naloxone in pre- and
      peripuberal heifers.
AB  - This study was conducted to investigate regulation of LH release by opioid
      peptides during puberal development in beef heifers. Fourteen heifers were
      randomly assigned to receive naloxone (opioid antagonist) i.v. at dosages of
      either 1 mg.kg BW-1.wk-1 (Dose 1) or .25 mg.kg BW-1.wk-1 (Dose 2) for 13 wk or
      until puberty. Blood was sampled (one sample every 15 min) 6 h before
      (prenaloxone) and 2 h after naloxone administration. Two hours after naloxone
      administration, GnRH (10 ng/kg BW) was administered and blood was sampled for 1
      h. Nine heifers attained puberty during the study. There were no differences
      between naloxone dosage groups for any measured variables. Therefore, heifers
      were grouped dependent on the attainment of puberty. Prenaloxone concentrations
      of serum LH and LH pulse frequency were normal for prepuberal heifers. Serum LH
      concentrations increased within 30 min after naloxone 135 of 139 times it was
      administered (P less than .05). Serum LH concentrations during the hour after
      naloxone were higher (P less than .05) than those during the hour before naloxone
      in both puberal and nonpuberal heifers. In puberal heifers, serum LH pulse height
      during the hour after naloxone was greater (P less than .02) at 5 wk before
      puberty and lower (P less than .02) the week before puberty than at other times
      during the trial. There was no effect of week on serum LH pulse height after
      naloxone in heifers that failed to attain puberty during the study. Response of
      LH to GnRH was similar between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399897
TI  - Ovarian follicular changes after weaning in sows.
AB  - Three experiments investigated ovarian follicular development in sows whose
      litters were weaned at 28 to 31 d of lactation. Unilateral ovariectomy near the
      time of weaning was used to assess early follicular characteristics and to
      identify those sows that would not return to estrus within 10 d after weaning.
      This allowed segregation of and exclusion from the study those sows that had a
      prolonged interval from weaning to first estrus. In Exp. 1, 82 and 72% of the
      large follicles that were marked at 48 or 72 h after weaning (10 sows per time
      point) were subsequently identified as corpora lutea. In Exp. 2, sows (seven to
      nine per time point) were unilaterally ovariectomized at 0, 6, 12, 18, 24, or 48
      h after weaning, and follicular fluid was evaluated for changes in steroid
      concentrations. Progesterone concentrations in fluid from medium-sized (4 to 6
      mm) follicles increased by 6 h after weaning and then declined through 24 h
      concomitant with increases in testosterone and estradiol. For Exp. 3, follicular
      fluid and granulosa cells from individual follicles were obtained from sows
      (seven to nine per time point) at 0, 6, and 24 h after weaning. In follicular
      fluid, insulin-like growth factor I (IGF-I) concentrations were not correlated (P
      greater than .05) with concentrations of progesterone, testosterone, or
      estradiol, or with granulosa cell production of estradiol during culture in
      androstenedione-supplemented medium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399898
TI  - Responses of calves to treadmill exercise during beta-adrenergic agonist
      administration.
AB  - Calves perorally administered the beta-adrenergic agonist (beta-A) clenbuterol
      for 28 d were studied before, during, and after a 12-min treadmill exercise.
      During exercise on d 1 of clenbuterol administration, respiratory rate,
      respiratory minute volume, and heart rate and blood glucose, lactate, and insulin
      concentrations increased more in beta-A-treated calves than in controls. Oxygen
      extraction rate and growth hormone concentrations were lower in clenbuterol
      treated calves, whereas oxygen consumption, carbon dioxide production, and blood
      cortisol concentration increased similarly in the absence and presence of the
      beta-A. After 2 wk of daily clenbuterol administration, respiratory rate and
      respiratory minute volume during exercise were still higher and oxygen extraction
      was still lower, whereas all other measures were similar to those in controls.
      The increased heart rate in response to isoproterenol after 3 wk of clenbuterol
      administration was reduced markedly in resting but only slightly in exercising
      animals, whereas heart rate reduction by propranolol during exercise was similar
      to that in controls. Seven days after withdrawal of clenbuterol, newly
      administered clenbuterol evoked the same effects as on d 1. In conclusion, there
      were marked reactions to the first clenbuterol treatment that were in part
      enhanced during treadmill exercise. After 2 wk of beta-A administration, animals
      responded much less to the beta-A and changes were not different from those in
      controls. Resensitization to the beta-A was observed 7 d after its withdrawal.

PMID- 1399899
TI  - Effects of melatonin treatment on the attainment of puberty in heifers.
AB  - This experiment determined the effect of treatment of 3- to 4-mo-old heifer
      calves with exogenous melatonin, in early summer, on the attainment of puberty
      the following spring. Hereford heifers, born between February 22, and March 16,
      were paired by age and BW and assigned at random within pair to receive an ear
      implant of melatonin (MEL, n = 12) or to serve as controls (C, n = 12). The
      implant period was 5 wk, starting June 10 at a mean age of 105 +/- 5 d and 134.4
      +/- 3.5 kg BW. Puberty was evaluated the following year on four occasions:
      January 26, March 19, May 2, and June 1. One each date, rectal palpation of the
      ovaries was performed, blood samples were taken to assess concentrations of
      progesterone (P4), and BW was determined. Puberty was considered to have occurred
      when concentrations of P4 were greater than or equal to .5 ng/mL concomitant with
      a palpable corpus luteum (CL), or when concentrations of P4 were greater than or
      equal to 1 ng/mL and a CL was present on the next date. At implant removal,
      concentrations of melatonin in plasma collected at 1000 to 1400 were 69.5 +/- 6.3
      and 16.7 +/- 2.4 pg/mL for MEL and C heifers, respectively. On that and
      subsequent occasions, neither BW nor ADG differed between MEL and C heifers.
      Treatment with melatonin increased the incidence of heifers pubertal by the
      second observation date (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399901
TI  - Responses of serum folates of preruminant and ruminant calves to a dietary
      supplement of folic acid.
AB  - The effect of dietary supplemental folic acid on serum folates of preruminant and
      ruminant calves was studied. In Trial 1, doses of 0, .07, .14, .28, and .56 mg of
      folic acid per kilogram of BW were added to the milk of preruminant calves. In
      Trial 2, doses of 0, .5, 1, 2, and 4 mg of folic acid per kilogram of BW were
      incorporated into the concentrates of ruminant heifers. In the first part of each
      trial, serum folates were determined in blood samples taken 0, 1, 2, 4, 8, 16
      (both trials), and 32 h (Trial 2) after a single meal supplemented with folic
      acid. In the second part of the two trials, the supplement of folic acid was
      given in feed during seven consecutive days. Blood samples were taken the day
      before the trial and subsequently every day during 7 d. In preruminant and
      ruminant calves, the area under the curve and the peak of concentration of serum
      folates after a meal increased with the dose ingested (P less than or equal to
      .05, linear and quadratic effect of doses, respectively) but the amount of folic
      acid needed to obtain a similar response was lower for preruminant than for
      ruminant calves. In preruminants, the time to reach the maximal concentration was
      3 to 4 h after the meal, whatever the dose ingested (P less than or equal to
      .05), whereas in ruminants this time decreased with the dose ingested (quadratic
      effect of treatment, P less than or equal to .05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1399900
TI  - Sulfate supplementation of Angora goats: metabolic and mohair responses.
AB  - Eight castrated male Angora goats were used in a repeated, simultaneous 4 x 4
      Latin square designed experiment to evaluate metabolic and mohair responses of
      Angora goats to sulfate supplementation. Goats had ad libitum access to
      isonitrogenous diets containing a .16 (basal), .23, .29, or .34% S (DM basis),
      which yielded N:S ratios of 12.7, 8.3, 6.8, or 5.5:1. Feed intakes were not
      affected (P greater than .20) by dietary S level. Quadratic increases (P less
      than .05) to S supplementation were observed in grease and clean mohair
      production, grease and clean staple strength, and staple length. Mohair diameter,
      med fiber, kemp fiber, S, and cysteine contents were not affected (P greater than
      .05) by supplemental S. Averaged across the prefeeding, 2, 4, and 6 h
      postprandial sampling times, ruminal pH, ammonia N, total S, organic S, protein
      S, and plasma urea N and organic S concentrations were quadratically increased (P
      less than .05) by supplemental S. Ruminal sulfate S, total sulfide S, and plasma
      sulfate S were linearly increased (P less than .05) by supplemental S. Retention
      of N and mohair S yield exhibited quadratic increases (P less than .05), but S
      retention exhibited a linear increase (P less than .001) with increased S intake.
      Calculated by regression, the optimum dietary S concentration for maximum clean
      mohair production was .267% of dietary DM for a N:S ratio of 7.2:1, suggesting
      that the National Research Council N:S ratio of 10:1 is inadequate for Angora
      goats. The optimum level of digestible S was calculated to be .18% of the diet
      DM.

PMID- 1399902
TI  - Effects of compensatory growth on some body component weights and on carcass and
      noncarcass composition of growing lambs.
AB  - A trial was conducted in 1983 and repeated in 1984 to measure effects of
      restricted feed intake and realimentation on weights of organs and on carcass and
      noncarcass composition. A total of one hundred six weaned lambs from two breeds
      (Timahdit and D'man) and a breed cross (Ile de France x D'man) were used in both
      years. Lambs were allotted to one of six feed intake regimens: HH (ad libitum
      access to feed from 21 to 30 kg); HM (ad libitum access to feed from 21 to 26 kg
      then 70% ad libitum to 30 kg); MH (70% ad libitum from 21 to 26 kg then ad
      libitum to 30 kg); MM (70% ad libitum from 21 to 30 kg); LH (restricted to lose
      weight from 21 to 17 kg then ad libitum to 30 kg); and LM (restricted to lose
      weight from 21 to 17 kg then 70% ad libitum to 30 kg). Weights of visceral organs
      and mesenteric and kidney fat showed dramatic responses to alteration of feed
      allowances. After recovery from 20% live weight loss, weight of liver equaled or
      exceeded that of both the ad libitum and 70% refed lambs. Mesenteric and kidney
      fat did not. Refeeding was accompanied by an increase in water (P less than .05)
      and a decrease in fat (P less than .01) of both carcass and noncarcass
      components. These results indicate that weight loss of lambs incurred during feed
      shortage was largely in internal organ weights, and that these lambs can recover
      these losses during realimentation and undergo compensatory growth with better
      feed efficiency and lean carcasses.

PMID- 1399903
TI  - Effects of undernutrition and refeeding on weights of body parts and chemical
      components of growing Moroccan lambs.
AB  - Forty-four intact, male lambs (20 Timahdit and 24 D'man) were used to assess the
      effects of 22% (from approximately 25 to approximately 20 kg) and 31% (from
      approximately 25 to approximately 17 kg) live weight loss and the subsequent
      refeeding to initial BW on changes in body components. Body composition was
      determined using a serial slaughter technique at 17, 20, and 25 kg live weight
      during normal growth, weight loss, and refeeding phases. Reduction in live weight
      from 25 to 20 kg was associated with greater loss of visceral organs (30%) and
      internal fat (75%) than carcass loss (19%). Further body weight loss (from 20 to
      17 kg) involved carcasses to a greater extent than internal organs. The
      composition of BW loss consisted of 53% water, 28% fat, and 15% protein.
      Refeeding was associated with a rapid increase in organ weights and less fat
      regeneration. Although total internal organs recovered only 90% of their original
      weight, liver and kidneys regained all their weight. At the same slaughter
      weight, carcass and noncarcass components of refed lambs were leaner because of
      lower fat content in these components.

PMID- 1399904
TI  - Effect of grain sorghum hybrid on in vitro rate of starch disappearance and
      finishing performance of ruminants.
AB  - Forty-eight commercial grain sorghum hybrids were ranked on the basis of in vitro
      starch disappearance (IVSD) and starch content. Starch content ranged from 64.3
      to 70.3% (P less than .01) and IVSD ranged from 5.2 to 6.3%/h (P less than .01).
      In the next year, 20 experimental grain sorghum hybrids consisting of 17 hybrids
      being developed for livestock diets and three for human diets were ranked
      according to IVSD, starch content, and CP content. In these samples, IVSD varied
      from 6.0 to 9.1%/h (P less than .05). Starch content and CP were not related to
      IVSD. Starch content was not correlated to CP content. Four of the original 48
      grain sorghum hybrids, selected on the basis of IVSD (two fast and two slow),
      that differed in IVSD by 7.0% (6.5 to 7.0%/h), were fed for 133 d to steers (mean
      initial BW of 326 kg). The ADG of steers fed Hybrid A (fastest IVSD) was 9.0%
      faster than that of steers fed Hybrid D (slowest IVSD; 1.33 vs 1.22 kg, P = .06).
      Gain:feed ratio was positively correlated with IVSD across all treatments (R2 =
      .94). Hybrids A and D, another Hybrid, A1, and a bird-resistant hybrid (BR) were
      fed for 85 d to finishing lambs (mean initial BW of 28 kg). Lambs fed Hybrid A
      gained more efficiently (gain:feed) than those fed BR or A1 (.210 vs .188 and
      .184, P less than .05), and those fed D were intermediate (.200). Performance of
      sheep fed A1, with the fastest IVSD, and those fed BR, with the lowest IVSD, were
      similar, suggesting that factors other than IVSD affected lamb performance. Our
      data indicate that rate of grain sorghum starch digestion may influence feeding
      value of grain sorghum fed to cattle.

PMID- 1399905
TI  - Plasma amino acid response to graded levels of escape protein.
AB  - A trial was conducted to examine the potential of using plasma amino acid
      responses to graded levels of escape protein to determine limiting amino acids in
      cattle. Growing calves (n = 120; mean BW = 220 +/- 21 kg) were fed a basal diet
      of corncob:sorghum silage (61:39) and were individually supplemented with
      distillers' dried grains (DDG), heat-damaged DDG (H-DDG), feather meal (FTH), or
      urea. The urea supplement was mixed with DDG and H-DDG to allow 0, 20, 35, 50,
      65, or 80% of the supplemental CP to come from distillers' protein and maintain
      an 11.5% CP diet. Urea supplement was mixed with FTH to allow 0, 22, 39, 56, 73,
      or 90% of the supplemental CP to come from FTH. Dietary CP ranged from 11.5% at
      the 0% level to 17.3% at the 90% level. Plasma concentration of most essential
      plasma amino acids responded (P less than .10) linearly and(or) quadratically to
      increased escape protein. The broken-line response of plasma methionine at low
      DDG intake suggested that methionine was limiting at low levels of escape
      protein. An initial decrease followed by a plateau fit by a broken line indicated
      that histidine became limiting in FTH diets, and lysine eventually became
      limiting for DDG, H-DDG, and FTH diets before maximum BW gain was reached.
      Results indicate that plasma amino acid responses may identify amino acids that
      become limiting with increasing escape protein.

PMID- 1399906
TI  - Influence of postfast dietary crude protein and phosphorus content on nitrogen,
      phosphorus, calcium, and magnesium repletion in sheep.
AB  - An experiment was conducted to determine the influence of postfast dietary CP and
      P concentration on the repletion of N, P, Ca, and Mg lost during a 3-d fast in
      sheep. Four Suffolk wether lambs averaging 35 kg were used in a 4 x 4 Latin
      square design. Lambs were fed a control diet (700 g/d; as-fed basis) for 14 d and
      were then deprived of feed and water for 3 d. Lambs were then fed one of four
      isoenergetic realimentation diets: 1) low CP/low P, 2) low CP/high P, 3) high
      CP/high P, and 4) high CP/very high P. Realimentation N and Mg intakes were 9.8
      and 1.1 g/d for lambs fed the low-CP diet and 18.1 and 1.7 g/d for lambs fed the
      high-CP diets, respectively. Realimentation P intakes were 1.40, 2.36, 2.66, and
      3.82 g/d for lambs fed Diets 1, 2, 3, and 4, respectively. Nitrogen, P, Ca, and
      Mg apparent digestibility and balance and serum urea N, free fatty acids, P, Ca,
      Mg, and alkaline phosphatase were determined during the prefast, fast, and
      realimentation periods. Lambs fed the high-CP diets had higher (P less than .05)
      N and P digestibility and balance than lambs fed the low-CP diet. Increasing the
      dietary P content did not affect (P greater than .15) P balance or digestibility.
      In general, the realimentation diet fed did not affect (P greater than .15) serum
      concentrations of free fatty acids, alkaline phosphatase, inorganic P, Ca, or Mg.

PMID- 1399907
TI  - Ruminant placental lactogens: structure and biology.
AB  - Ruminant placental lactogens (PL) are members of the somatotropin, prolactin gene
      family that are synthesized by trophectodermal binucleate cells. The structure
      and biology of PL has been studied in the cow, sheep, and goat. Ruminant PL have
      greater structural identity to prolactin than somatotropin, although they bind to
      both lactogenic and somatogenic receptors. The molecular weights of ovine and
      caprine PL are approximately 23,000, whereas bovine PL is larger (31,000 to
      34,000) due to glycosylation. Placental lactogen is secreted into both the fetal
      and maternal circulations. The concentration of PL in the fetus decreases with
      advancing gestation, whereas PL concentration peaks in the maternal circulation
      during the last third of pregnancy then reaches a plateau. Furthermore, the
      maternal concentration of PL is 100- to 1,000-fold higher in sheep and goats than
      in cows. The precise factors that modulate secretion of PL are unknown, although
      placental mass and nutrition seem to play a role. Ruminant PL have both
      lactogenic and somatogenic biological activities and may also have unique
      activities mediated through a specific receptor. There is circumstantial evidence
      to suggest that PL plays a role in stimulating mammogenesis. Placental lactogen
      secreted into the fetal compartment may also help regulate fetal growth. Direct
      experimental data indicate that PL can regulate maternal intermediary metabolism.
      Thus, it may act as a partitioning agent to regulate nutrient supply for fetal
      growth. The precise biological function of PL in ruminants, therefore, still
      needs to be defined.

PMID- 1399908
TI  - The distribution of homologous enterococcal plasmid DNA sequences in human faecal
      isolates.
AB  - Hybridization was used to investigate the distribution of enterococcal plasmid
      sequences among 306 strains of Enterococcus and Streptococcus spp. isolated from
      faeces of humans of various ages. As DNA probes for the survey three plasmids,
      whose DNAs did not hybridize each other and designated as pMS13, pTW34 and pHK30,
      were selected from plasmids borne in Ent. faecalis. pTW34 DNA hybridized only
      with DNAs from enterococci, with high frequency in Ent. faecalis and low
      frequency in Ent. faecium. pMS13 DNA hybridized with DNAs of all Enterococcus
      spp. tested and with Strep. bovis, Strep. equinus and Strep. salivarius. Eighty
      five percent of Ent. faecium isolates had sequences homologous to pMS13 but in
      the other species the values were less than 60%. Some enterococci had DNAs which
      hybridized with the pHK30 probe. The different distribution of the three DNA
      sequences indicates the possibility that plasmid DNAs encode advantageous
      phenotypes for the colonization of bacteria in the lumen of the bowel.

PMID- 1399909
TI  - Evaluation of four membrane filter media in anaerobic-MF recovery of faecal
      coliforms from freshwater in Nigeria.
AB  - MacConkey (MC), membrane lauryl sulphate (MIS), membrane faecal coliform amended
      with rosolic acid (MFC + R) and without the acid (MFC - R) were evaluated in the
      anaerobic membrane filtration (anaerobic-MF) recovery of faecal coliform
      populations (FCs), genera and faecal coliform positive (FC-positive) strains
      isolated from various sources of freshwater, i.e., rivers, rural wells,
      unchlorinated distributive supplies and hand pumps. Mean counts (x 10(2)/100 ml)
      of presumptive (typical) FCs varied from 13.69 (MC) to 40.81 (MLS) in river
      samples, and from 2.0 (MC) to 4.19 (MFC + R) in wells. The proportion of FC
      positive, typical FCs ranged from 48.66 (MIS) to 66-67% (MC) in rivers, and from
      50 (MC) to 90.22% (MFC + R) in wells. More than 30% of the typical FCs from all
      sources on each medium was FC-negative. These usually formed small (ca 1.0 mm
      diam.) colonies on the test agar, and were prevalent in wells. Typical FCs and FC
      positive strains were not recovered from piped supplies and hand pumps. In spite
      of anaerobic incubation, non-faecal coliforms (NFCs) were often higher than the
      FCs; the FC:NFC ratios for rivers ranged from 1.65 (MC) to 7.65 (MLS) and (MFC +
      R) but were < 1.0 for wells on each medium. Escherichia coli, Klebsiella and
      Enterobacter species were recovered on all media: approximately 35-64% of the
      strains confirmed as FCs were E. coli, 20-42% were Kl. pneumoniae. The FC counts
      on the media were variable, but the overall performance in recovering 'true' FCs
      was similar; < 70% of strains per medium were FC-positive. None could count E.
      coli exclusively.

PMID- 1399910
TI  - Microbiological quality of bottled water sold in retail outlets in Nigeria.
AB  - The microbiological quality of four brands of bottled water sold in retail
      outlets in Nigeria were assessed by routine methods in 90 samples. Samples of two
      brands were acidic in the pH range 3.5-5.9. Faecal coliforms and streptococci
      were not recovered from any sample. Heterotrophic plate counts (HPC) numbered 50
      800 cfu/ml in two brands, A and B, and 100-87,000 cfu/ml in C and D. Component
      colony types among the HPC bacteria in brands C and D produced water-soluble,
      fluorescent pigments on colony count and other agar media, and occurred in 11 of
      16 batches: their numbers varied from 60 to 82,000 cfu/ml. Presumptive antibiotic
      resistant proportions of the HPC bacteria were also recovered from brands C and D
      on agar amended with ampicillin, penicillin or streptomycin. Five isolates from
      the green pigmented colonies, representing five batches of brands C and D were
      satisfactorily identified as strains of Pseudomonas aeruginosa. These strains
      resisted between four and nine of 14 antibiotics tested. Resistance to
      tetracycline was eliminated in one isolate when it was cured by incubation at 42
      degrees C for 100 h, but gel electrophoretic resolution of the DNA did not reveal
      presence of a plasmid. Strains of Bacillus were the second most commonly isolated
      bacteria; they were the only colony types in most samples with low HPC counts.

PMID- 1399911
TI  - The relationships between salmonellas and faecal indicator concentrations in two
      pools in the Australian wet/dry tropics.
AB  - The relationships between total coliform, faecal coliform, enterococci and
      salmonella concentrations were investigated at Berry and Howard Pools in the
      Australian wet/dry tropics. Both pools have catchments with minimal human
      activity and no major point source of faecal pollution. Forty-five indicator and
      salmonella enumerations were made from each pool over a 1 year period.
      Salmonellas were isolated from 69% and 96% of samples collected from Howard and
      Berry Pools respectively, the maximum (MPN) concentration was 110/100 ml. Native
      fauna were the primary salmonella source. Spearman rank correlations between
      indicator organisms and salmonella at Howard Pool were significant at the 5%
      level and approximated 0.6. At Berry Pool, total coliform and enterococci
      Spearman rank correlations with salmonella were also statistically significant,
      approximating 0.3; faecal coliforms and salmonella rankings, however, were
      unrelated. The higher correlation coefficients at Howard Pool were attributed to
      its small catchment (4 km2) and the more recent nature of faecal contamination
      compared with Berry Pool which has a catchment of 130 km2. The results highlight
      the spatial variability of the indicator/pathogen numerical relationship. Total
      coliform and enterococci counts, as indicators of faecal pollution, were similar
      and more consistent than faecal coliforms.

PMID- 1399912
TI  - Experimental enzyme-linked amperometric immunosensors for the detection of
      salmonellas in foods.
AB  - Two enzyme-linked amperometric immunosensors specific for salmonellas were
      developed as rapid methods for quantifying and detecting these organisms in pure
      cultures and foods. Both used alkaline phosphatase as the enzyme reporter
      molecule but one system used phenyl phosphate as the substrate followed by the
      electrochemical detection of phenol at a polarized platinum electrode. The other
      system incorporated an enzyme amplification step and relied on the
      electrochemical detection of a reduced mediator, ferrocyanide. Both assays were
      rapid (4 h) and specific and generated salmonella-dependent signals above 10(4)
      cfu/ml (phenyl phosphate system) or 10(5) cfu/ml (enzyme amplified system) in
      pure cultures and samples of several foods, although the results with beef
      samples showed considerable variation. Both systems were able to detect low (1-5
      cfu/g or /ml) numbers of salmonellas in foods after non-selective (18 h) and
      selective (22 h) enrichment steps but four samples, out of 147, gave false
      positive results. False positive results were eliminated by reducing the
      enrichment steps to 6 h and 18 h respectively (90 samples).

PMID- 1399913
TI  - Incidence of toxigenic vibrios in foods available in Taiwan.
AB  - A total of 1088 vibrios and related species were isolated from seafood and
      aquacultured foods available in Taiwan. They were identified as Vibrio
      alginolyticus, V. cholerae, V. fluvialis I, V. fluvialis II, V. parahaemolyticus,
      V. mimicus, Aeromonas caviae, A. hydrophila, A. sobria and other species.
      Incidence of these Vibrio and Aeromonas species in these foods was high. Vibrio
      parahaemolyticus was frequently found in seawater and in foods of freshwater
      origin. The Vibrio isolates were examined for enzymatic and toxigenic activities.
      Most of them showed strong lipase or protease activities. Haemolytic activities
      of V. cholerae, V. fluvialis I and V. fluvialis II isolates were mostly strong.
      About 49% showed cytotoxic activity and 5% cytotonic activity in Chinese hamster
      ovary cell culture assay. Nevertheless, only three non-O1 V. cholerae (2.07%) and
      two V. parahaemolyticus isolates (1.65%) produced cholera toxin and thermostable
      direct haemolysin activity, respectively. Various toxigenic vibrios may be
      important food-borne pathogens in this region because of their high incidence in
      foods.

PMID- 1399914
TI  - Microbiological events during commercial meat fermentations.
AB  - Microbiological developments during industrial meat fermentations (salami), made
      with and without commercial starter cultures, were followed at two factories in
      Germany and Italy. In the German product microbial growth was evident only for
      the first 48 h, followed by a gradual decline in numbers of most micro-organisms.
      The pH fell from 5.8 to 4.8 in the 28 d required for production. In Italy a
      similar situation was seen, except that a second period of bacterial growth began
      around 15 d, coincident with the appearance of intentional surface mould growth
      which reversed the pH fall, the final pH being 6.2. The German starter culture
      was a mixture of Lactobacillus plantarum and Staphylococcus carnosus, whereas in
      Italy only Staph. carnosus was used. The strain of Lact. plantarum used did not
      grow in the German product whereas the Staph. carnosus grew well in both products
      to form a substantial proportion of the final microflora.

PMID- 1399915
TI  - Laboratory performance in a food microbiology proficiency testing scheme.
AB  - Results from two shipments in a proficiency testing scheme in which almost 200
      food microbiology laboratories participated are summarized. Freeze-dried mixtures
      of bacteria were used as simulated food samples. Four and six samples,
      respectively, were examined. The statistical procedures used to evaluate the
      performance of participating laboratories are described. It is shown that
      laboratories which had been in the scheme for a long time perform, on average,
      better than those that had been in the scheme for a short time. The former
      laboratories produced fewer false and outlying results, and were more accurate
      and precise in their determinations.

PMID- 1399916
TI  - Survival strategies of plasmid-carrier and plasmidless Escherichia coli strains
      under illuminated and non-illuminated conditions, in a fresh water ecosystem.
AB  - A comparative study, in illuminated and non-illuminated systems, was made to
      determine the survival strategies of plasmid-carrier and plasmidless bacteria in
      sterile river water. Two strains of Escherichia coli from river water were
      selected: one plasmidless, EC1, and one antibiotic-resistant strain, EC7, which
      showed plasmid bands. By matings with EC7 as donor and E. coli K12 strain J62 as
      recipient, transconjugants were generated, the J62(7) strain, which showed both
      antibiotic resistance and plasmid bands. Ethidium bromide curing of the EC7
      strain generated the EC7(2) strain which showed a partial loss of resistance and
      a reorganization of plasmid bands. Under non-illuminated conditions the total
      number of cells detected by direct count and the number of culturable cells
      (injured and non-injured cells) remained practically constant throughout the
      period of incubation. In the illuminated systems, however, the number of cfu
      decreased in four of the five strains studied. The greatest decreases are those
      of the J62 strain, followed by those of the J62(7), EC1, EC7(2) and EC7 strains.
      Differences in survival strategies as a consequence of the presence or absence of
      plasmids are discussed.

PMID- 1399917
TI  - Two beta-glucosidase activities in Fibrobacter succinogenes S85.
AB  - Few bacteria are capable of degrading crystalline cellulose but there is
      considerable interest in the properties of enzyme systems with this capability.
      In the bovine and ovine rumen the principal cellulolytic bacterium is Fibrobacter
      (formerly Bacteroides) succinogenes. The cellulase system of this organism is
      composed of multiple enzyme components, including a constitutive and cell
      associated beta-glucosidase active against cellobiose. The properties of the beta
      glucosidase activity have been investigated with the chromogenic substrate p
      nitrophenyl beta-D-glucoside (pNPG). Hydrolytic activity against pNPG was located
      primarily in the cytoplasm and the cytoplasmic membrane but showed a gradual
      migration to the periplasm during growth on either glucose or cellobiose.
      Activity against cellobiose was found in the periplasm in significant amounts in
      all growth phases. Of the beta-glucosides tested, only cellobiose and pNPG were
      hydrolysed by crude cell extracts. In the presence of cellobiose, however, the
      rate of hydrolysis of pNPG was stimulated up to 10-fold, and extracts hydrolysed
      methylumbelliferyl beta-D-glucoside, 5-bromo-4-chloro-3-indolyl beta-D-glucoside,
      arbutin and aesculin. Activities against pNPG in the presence and absence of
      cellobiose displayed similar instability in the presence of oxygen; both were
      stabilized by dithiothreitol and the temperature and pH optima were identical. A
      significant proportion of the membrane-associated beta-glucosidase was released
      by treatment with 0.3 mol/1 KCl, and fractionation by chromatography on CM
      cellulose showed the presence of two activities against pNPG, only one of which
      was stimulated by cellobiose.

PMID- 1399918
TI  - Influence of the sporulation temperature upon the heat resistance of Bacillus
      subtilis.
AB  - The influence of different sporulation temperatures (30, 37, 44 and 52 degrees C)
      upon heat resistance of Bacillus subtilis was investigated. Heat resistance was
      greater after higher sporulation temperatures. Relation of heat resistance and
      temperature of sporulation was not linear over all the range of temperatures
      tested. Heat resistance increased about tenfold in the range of 30-44 degrees C.
      Sporulation at 52 degrees C did not show any further increase in heat resistance.
      This effect was constant over all the range of heating temperatures tested (100
      120 degrees C). z value remained constant (z = 9 degrees C). Greater heat
      resistances at higher temperatures of sporulation were not due to selection of
      more heat resistant cells by a higher sporulation temperature. Spores obtained
      from cells incubated at 32 or 52 degrees C always possessed heat resistances that
      corresponded to the sporulation temperature regardless of the incubation
      temperature of their vegetative cells.

PMID- 1399919
TI  - Sensitivity of Escherichia coli cells to seawater closely depends on their growth
      stage.
AB  - Sensitivity of Escherichia coli cells in seawater, considered in terms of
      culturability loss, was examined after different growth periods in a mineral
      medium supplemented with glucose (M9) at 37 degrees C under aerobic or anaerobic
      conditions. Their sensitivity varied considerably during the different growth
      phases and differed when cells were grown under aerobic or anaerobic conditions.
      Sensitivity of aerobic cells rapidly increased during the lag phase, then
      decreased during the exponential phase and became minimal during the stationary
      phase. Coliforms isolated from human faeces showed a similar sensitivity after
      incubation in wastewater at 37 degrees C for 3 h. The sensitivity phase was
      completely eliminated when cells were incubated with chloramphenicol. Variation
      of sensitivity in anaerobic cells according to their growth phase was comparable
      with that found for aerobic cells which had been left in seawater for a long
      period (6 d). However, for shorter periods in this medium (1-2 d), cells grown
      until the mid-exponential phase remained resistant to seawater. During the second
      half of the growth phase, they were as sensitive as aerobic cells at lag phase.
      Escherichia coli cells grown under anaerobic conditions, such as found in the
      intestine, progressively adapt to aerobic conditions after their transfer into
      aerated seawater and their sensitivity to seawater increases. On a practical
      level, these observations show that it is necessary to control accurately the age
      of cells before inoculation in seawater microcosms to conserve a comparative
      value in results. The importance of this factor is vital as all variations in
      sensitivity of cells to seawater according to their prior growth phase proved to
      be logarithmic functions of time.

PMID- 1399920
TI  - Coliform bacteria from aquatic sources in Fiji.
AB  - Coliform bacteria were abundant in water and bivalve molluscs in the rivers and
      present to a lesser extent in the coastal areas of Fiji. The rivers fed by
      treated sewage were highly polluted. There was a noticeable increase in
      concentration of coliforms in bivalve molluscs. It was also found that these
      bacteria could survive and grow in river water and seawater over a 5-d period,
      and had a rapid growth rate in nutrient broth under ideal laboratory conditions.
      They were characterized by the API 20E identification system.

PMID- 1399921
TI  - Characterization of the plasmid mediated beta-lactamase BIL-1.
AB  - A multi-resistant strain of Escherichia coli isolated from a patient from
      Pakistan was shown to possess a new plasmid-mediated beta-lactamase. This enzyme,
      designated BIL-1, conferred resistance to extended-spectrum cephalosporins such
      as cefotaxime and ceftazidime. However, unlike other plasmid-mediated beta
      lactamases capable of conferring resistance to these drugs, the BIL-1 was not a
      member of the TEM or SHV group of plasmid-mediated beta-lactamases and it also
      conferred resistance to beta-lactam drugs in combination with beta-lactamase
      inhibitors (i.e. clavulanic acid). The biochemical properties of the enzyme
      suggest that BIL-1 is related to the Richmond & Sykes Class I chromosomal beta
      lactamases. Its inhibition properties by various beta-lactam drugs are similar to
      the inhibition properties of the chromosomally-encoded P99 enzyme of Enterobacter
      cloacae.

PMID- 1399922
TI  - In-vitro efficacy of a central venous catheter complexed with iodine to prevent
      bacterial colonization.
AB  - Infections of central venous lines are still a problem in daily medicine. Despite
      adequate antibiotic therapy, removal of an infected catheter often becomes
      necessary. A simple procedure has been developed by which a special hydrophilic
      central venous catheter (Secalon-Hydrocath) can be loaded with iodine. Iodine is
      complexed in the hydrophilic polyvinylpyrrolidone surface coating of the
      Hydrocath catheter and is released during contact with an aqueous medium. The
      amount of complexed iodine depends on the incubation time in Lugol's solution.
      Antimicrobial activity of the loaded catheters was assessed with Staphylococcus
      epidermidis, showing complete inhibition of bacterial adherence to the catheters
      for the duration of iodine release. Depending on the experimental conditions,
      iodine released from the catheter is also active on bacteria in the surrounding
      medium.

PMID- 1399923
TI  - Ciprofloxacin and Clostridium difficile-associated diarrhoea.
AB  - Recent reports have implicated ciprofloxacin as a cause of Clostridium difficile
      associated diarrhoea. This problem was examined in three ways. First, the MIC of
      ciprofloxacin for C. difficile was determined. The MIC range was 8-32 mg/L, with
      C. difficile were 'treated' with ciprofloxacin and clindamycin in a test-tube,
      and the growth of C. difficile monitored. The clindamycin-treated emulsions
      supported growth of C. difficile, while the ciprofloxacin-treated and control
      emulsions did not differ significantly and failed to support the growth of C.
      difficile. Finally, 213 patients on ciprofloxacin monotherapy were investigated.
      Twenty-nine patients were given ciprofloxacin as treatment for diarrhoea, while a
      further 15 patients developed diarrhoea while being treated. None of these 44
      patients harboured C. difficile. Faecal samples from 73 of the remaining 169
      patients who did not have or develop diarrhoea were investigated for C.
      difficile, but none was positive. It was concluded that ciprofloxacin is unlikely
      to promote C. difficile-associated diarrhoea.

PMID- 1399924
TI  - Susceptibility of Pseudomonas aeruginosa to fluoroquinolones following four years
      of use in a tertiary care hospital.
AB  - Of 121 recent clinical isolates of Pseudomonas aeruginosa, 22% were resistant to
      ciprofloxacin, 50% to ofloxacin and 69% to pefloxacin. Resistance to these drugs
      was commonest among urinary isolates (P less than 0.03). Cross-resistance was
      noted between fluoroquinolones and aminoglycosides or beta-lactams.

PMID- 1399925
TI  - A national collaborative study of resistance to antimicrobial agents in
      Haemophilus influenzae in Australian hospitals. The Australian Group for
      Antimicrobial Resistance (AGAR).
AB  - An Australia-wide survey of the prevalence of resistance to antimicrobial agents
      among Haemophilus influenzae was conducted on clinically significant isolates
      collected between July 1988 and September 1990. Laboratories from the capital
      cities of each Australian state and territory participated. Nine hundred and
      seventy clinical isolates were examined for beta-lactamase production and the
      MICs of ampicillin, coamoxiclav, chloramphenicol, cefaclor, ceftriaxone,
      cefotaxime, tetracycline, rifampicin, trimethoprim, sulphamethoxazole and co
      trimoxazole were determined using the NCCLS agar dilution method with Haemophilus
      Test Medium. A smaller number of isolates were tested against penicillin V,
      penicillin G, ciprofloxacin, piperacillin and erythromycin in addition. The
      proportion of beta-lactamase producing strains was higher among invasive strains
      (21.6%) than non-invasive strains (14.2%) and varies considerably between states.
      The highest prevalence of ampicillin resistance was found in invasive strains
      from Canberra (40.8%), the lowest in non-invasive strains from Adelaide (5.1%).
      Paradoxically, in non-invasive strains, although beta-lactamase production was
      less common, resistance to other antimicrobials was commoner than in invasive
      strains and also varied between states.

PMID- 1399926
TI  - Bactericidal activity of beta-lactams and amikacin against Haemophilus
      influenzae: effect on endotoxin release.
AB  - Ampicillin or cefotaxime, alone or in combination with amikacin, were tested at
      levels achievable in CSF for bactericidal activity against eight clinical
      isolates of Haemophilus influenzae serotype b. Endotoxin release was determined
      by the limulus amoebocyte lysate test and by macrophage tumour necrosis factor
      production for each beta-lactam antibiotic, alone and in combination with
      amikacin. Accelerated killing was observed when amikacin was added to ampicillin
      or cefotaxime; however, the additional antibiotic-induced bacterial lysis
      observed after the addition of amikacin to beta-lactam antibiotics was not
      associated with an increase in endotoxin release.

PMID- 1399927
TI  - Effect of nanoparticle-bound ampicillin on the survival of Listeria monocytogenes
      in mouse peritoneal macrophages.
AB  - The efficacy of ampicillin bound to polyisohexylcyanoacrylate nanoparticles was
      studied in vitro in mouse peritoneal macrophages infected with Listeria
      monocytogenes. Nanoparticles containing ampicillin 1 mg/L were more effective
      after 30 h than free ampicillin at the same concentration, with viable counts of
      3.68 and 5.43 log10 cfu/mL, respectively. The nanoparticles acted on the
      intracellular bacteria after a lag period of 6-9 h; this time was apparently
      required for the degradation of the polymer. At the doses used in these
      experiments, empty nanoparticles had neither an anti-listeria nor a cytotoxic
      effect.

PMID- 1399928
TI  - Disposition of roxithromycin in the epididymis after repeated oral
      administration.
AB  - The epididymal penetration of roxithromycin was studied in order to evaluate the
      drug for use in the treatment of epididymo-orchitis. Seventeen patients
      hospitalized for surgery as part of treatment for prostatic adenoma or prostatic
      cancer were premedicated orally with roxithromycin 150 mg bd for three days
      followed by 150 mg pre-operatively (3 h before surgical incision). Roxithromycin
      concentrations in serum and epididymis were determined by microbiological assay.
      The mean epididymal concentrations were 6.48 +/- 4.88 and 5.98 +/- 3.92 mg/kg for
      left and right epididymis respectively and the corresponding mean tissue/serum
      ratios 0.88 +/- 0.57 and 0.84 +/- 0.53. The wide intersubject variation in the
      concentration of roxithromycin found in serum and tissue is commonly seen with
      other macrolide antibiotics. The concentrations observed in this study in serum
      and tissue were greater than the MIC90s for Chlamydia trachomatis (0.25 to 1
      mg/L), and Ureaplasma urealyticum (0.5 mg/L).

PMID- 1399929
TI  - A randomized trial of high-dose ciprofloxacin versus azlocillin and netilmicin in
      the empirical therapy of febrile neutropenic patients.
AB  - A prospective, randomized trial comparing monotherapy with high-dose
      ciprofloxacin versus a standard combination regimen of azlocillin and netilmicin
      in the empirical treatment of febrile episodes in neutropenic patients was
      performed. One hundred and forty-six patient episodes were randomized, but ten
      (seven ciprofloxacin and three azlocillin/netilmicin) were considered unevaluable
      for efficacy, and three episodes were withdrawn due to incorrect randomization or
      non-neutropenia. Of the remaining 133 episodes, infections resolved without
      modification of therapy in 25/66 (38%) versus 28/67 (42%) of ciprofloxacin and
      azlocillin/netilmicin treated groups respectively (P = 0.72). Considering all
      randomized episodes, therapy was modified in 46/73 (63%) episodes with
      ciprofloxacin and 39/70 (56%) with azlocillin/netilmicin (P = 0.40). Of 73
      patient episodes randomized to ciprofloxacin, 25 (34%) received oral follow-on
      therapy after a median of three days of intravenous therapy. Infections were
      microbiologically documented in 31/73 (42%) ciprofloxacin and 32/70 (46%)
      azlocillin/netilmicin, of which 8/27 (30%) and 14/31 (45%) of evaluable episodes
      resolved without modification of therapy respectively (P = 0.28). Gram-positive
      organisms accounted for 78% of all organisms cultured with 36% coagulase-negative
      staphylococci. Bacteriological eradication was recorded in 18/24 (75%) and 26/29
      (90%) evaluable patient episodes treated with ciprofloxacin and
      azlocillin/netilmicin respectively (P = 0.27). Superinfections were seen in 14%
      of episodes in both groups, and subsequent infections in 12% ciprofloxacin and
      14% azlocillin/netilmicin treated patients. Two patients (one ciprofloxacin and
      one azlocillin/netilmicin) died within 48 h of randomization, and a further 13
      patients (four ciprofloxacin and nine azlocillin/netilmicin) died before
      resolution of neutropenia. Adverse events were recorded in 9% and 15% of
      ciprofloxacin and azlocillin/netilmicin treated patients respectively, with skin
      rash (five ciprofloxacin and four azlocillin/netilmicin), nephrotoxicity (two
      azlocillin/netilmicin), abnormal liver function tests (two
      azlocillin/netilmicin), ototoxicity (one azlocillin/netilmicin) and nausea (one
      ciprofloxacin) being the major events recorded. It was concluded that monotherapy
      with ciprofloxacin at this dosage is a safe alternative to combination therapy
      with azlocillin/netilmicin, and has the advantages of twice daily administration,
      iv and oral presentations, no cross allergy in beta-lactam-hypersensitive
      patients, and no nephro- or oto-toxicity.

PMID- 1399930
TI  - An open, comparative trial of aztreonam with vancomycin and gentamicin with
      piperacillin in patients with fulminant hepatic failure.
AB  - Fifty patients admitted with fulminant hepatic failure and clinically suspected
      infection were allocated to receive either aztreonam and vancomycin or
      piperacillin and gentamicin as first line treatment. Fourteen patients died
      within 48 h of admission and were excluded from the analysis. Of the remaining 36
      patients, 16 received aztreonam/vancomycin and 20 piperacillin/gentamicin. There
      were 18 episodes of infection in the aztreonam/vancomycin group and 24 in the
      piperacillin/gentamicin group (P = not significant). The most frequent bacterial
      pathogen was Staphylococcus aureus. Fungal infection developed in 13 patients
      (nine in the aztreonam/vancomycin group and four in the piperacillin/gentamicin
      group; P = not significant). Death attributed to infection occurred in 4 (25%) of
      16 patients receiving aztreonam/vancomycin and 4 (20%) of 20 receiving
      piperacillin/gentamicin (P = not significant). Thirteen patients (three in the
      aztreonam/vancomycin group and ten in the piperacillin/gentamicin group) had
      clinical and microbiological improvement without addition or substitution of
      other antibiotics. No side-effects attributed to the study drugs were recorded.

PMID- 1399931
TI  - Quinolones and Salmonella gastroenteritis.

PMID- 1399932
TI  - Activity of amoxycillin clavulanic/acid against Escherichia coli in vivo.

PMID- 1399933
TI  - High-level quinolone resistance in Pseudomonas aeruginosa.

PMID- 1399934
TI  - The post-antibiotic effect of imipenem and penicillin-binding protein 2.

PMID- 1399935
TI  - In-vitro selection of ampicillin-resistant non-beta-lactamase-producing
      Haemophilus influenzae strains.

PMID- 1399936
TI  - Inactivation of ceftriaxone by faecal enzyme preparations during ceftriaxone
      treatment.

PMID- 1399937
TI  - Activity of the antimycotic ketoconazole against Helicobacter pylori.

PMID- 1399938
TI  - Effect of quinolones on human neutrophil chemotaxis.

PMID- 1399939
TI  - RP 59500: a semi-synthetic injectable streptogramin antibiotic.

PMID- 1399940
TI  - Antimicrobial activity against Staphylococcus aureus of semisynthetic injectable
      streptogramins: RP 59500 and related compounds.
AB  - Pristinamycin displays unique antibacterial properties due to the synergy between
      its two components, pristinamycin I and pristinamycin II. Because this antibiotic
      is not water-soluble, its administration is restricted to the oral route, and its
      therapeutic potential is thereby limited. Novel water-soluble derivatives of the
      naturally-occurring antibiotic pristinamycin were obtained by modifications of
      its two major components. The modifications included regioselective and
      stereoselective substitution alpha to the carbonyl group in the 4-oxo-pipecolic
      acid residue of pristinamycin IA (PIA) and stereoselective conjugate addition to
      the double bond of the dehydroproline ring in pristinamycin IIA (PIIA). We report
      here the in-vitro and in-vivo activities of some representative water-soluble
      derivatives of pristinamycin IA and pristinamycin IIA against Staphylococcus
      aureus reference strains, sensitive or resistant to methicillin and/or
      macrolides.

PMID- 1399941
TI  - Post-antibiotic effects of RP 59500 with Staphylococcus aureus.
AB  - The post-antibiotic effect (PAE) of the semisynthetic streptogramin RP 59500 was
      evaluated with four clinical isolates of Staphylococcus aureus (two strains
      susceptible to methicillin and to the macrolide-lincosamide-streptogramin B
      (MLSB) group and two strains resistant to these drugs). The PAE was defined as
      the time required for either the viable counts to increase by one log10 or for
      bacteria to regain their maximal rate of growth. Similar results were obtained
      regardless of which definition was used. For each experiment, the time of
      exposure of the bacteria to the drug ranged from 15-80 min. At a concentration of
      0.5 x MIC and an exposure time of 80 min, RP 59500 produced a PAE in three of the
      four strains examined. At higher concentrations (1, 2 and 4 x MIC), a PAE was
      observed with all four strains. When considered as the time required for
      bacterial growth to return to its maximal rate, the PAE lasted for at least 7 h
      with the two methicillin-susceptible strains when they were exposed for 80 min to
      RP 59500 at 4 x MIC, compared with 5 h for the two methicillin-resistant strains
      and the same exposure conditions. The concentration of antibiotic was found to be
      a more important parameter in determining the PAE than the time of exposure.

PMID- 1399942
TI  - Cellular uptake and intracellular bactericidal activity of RP 59500 in murine
      macrophages.
AB  - RP 59500, a new antibacterial agent, is a combination of two compounds, RP 54476
      and RP 57669. The uptake of radiolabelled RP 59500, i.e. a mixture containing
      [14C]-RP 54476 plus RP 57669 or [14C]-RP 57669 plus RP 54476, by J 774 murine
      macrophages was evaluated by a velocity gradient centrifugation technique. After
      120 min, the ratios of cellular to extracellular concentration for RP 54476 and
      RP 57669 were 34 and 50, respectively. The highest intracellular accumulation of
      RP 59500 was observed at pH 7-7.5. RP 59500 was found to accumulate less at 4
      degrees C than at 37 degrees C. The uptake of RP 59500 by dead macrophages was
      markedly higher than that by live macrophages. As the extracellular concentration
      of RP 59500 was increased, the intracellular concentration of each component
      rose, but not proportionally. The metabolic inhibitors sodium cyanide and
      potassium fluoride both decreased modestly the entry of RP 57669, but not that of
      RP 54476, into macrophages. After removal of the extracellular antibiotic, RP
      54476 and RP 57669 were released rapidly by the cells until equilibrium was
      established (45% of the original intracellular RP 59500 remained in the cells
      after 120 min). The intracellular activity of RP 59500 was assessed by incubating
      macrophages containing ingested Staphylococcus aureus 209P with the drug (10 x
      MIC: 2.5 mg/L) at 37 degrees C and determining the number of viable cell
      associated bacteria. Approximately 70% of the intracellular bacteria were killed
      within 120 min of incubation. Thus, RP 59500 attains a high intracellular
      concentration and is active against intracellular S. aureus.

PMID- 1399944
TI  - A phase I, double-blind, placebo-controlled study of the tolerance and
      pharmacokinetic behaviour of RP 59500.
AB  - The tolerance and pharmacokinetic behaviour of a new injectable streptogramin
      antibiotic, RP 59500 were evaluated on 26 healthy male volunteers in a double
      blind, placebo-controlled, phase I study. The doses used were 1.4, 2.8, 4.6, 7.0,
      9.8, 12.6, 16.8, 22.4 and 29.4 mg/kg; each dose was administered as a 1 h
      infusion to eight subjects, two of them receiving placebo. Blood levels of RP
      59500 were measured by both microbiological and HPLC assays. At the end of the
      infusion, Cmax for RP 59500 ranged from 0.95 +/- 0.22 to 24.20 +/- 8.82 mg/L. The
      apparent elimination half-life of the compound ranged from 1.27 to 1.53 h. RP
      59500 did not significantly affect any of the laboratory or clinical assessments
      (blood pressure, pulse rate, ECG, peak expiratory flow rate). Reported adverse
      effects were of mild intensity; the most frequent event was mild pain or burning
      at the infusion site with doses of 7 mg/kg or higher. These results support
      further studies of RP 59500 in phase II clinical trials.

PMID- 1399943
TI  - Studies of RP 59500 in vitro and in a rabbit model of aortic valve endocarditis
      caused by methicillin-resistant Staphylococcus aureus.
AB  - The activity of RP 59500 against methicillin-resistant Staphylococcus aureus was
      studied in vitro and in a rabbit model of aortic valve endocarditis. Three
      strains, 67-O, 529, and Du, ranging from relatively resistant to susceptible to
      RP 59500 in vitro (mean agar dilution MICs of 0.65, 0.21, and 0.12 mg/L
      respectively) were used to establish endocarditis, which was treated either with
      RP 59500, 20 mg/kg im four times a day for four days or with vancomycin, 25 mg/kg
      iv twice a day for four days. RP 59500 was ineffective for the most resistant
      strain, 67-O. RP 59500 was effective for the intermediately susceptible strain
      529, but vancomycin was more effective. RP 59500 was slightly more effective than
      vancomycin against the most susceptible strain, Du, but the difference was not
      statistically significant. These results suggest that strains inhibited by RP
      59500 at a concentration of greater than or equal to 0.5 mg/L should probably be
      considered resistant in this model of infection. RP 59500 was effective in vivo
      against the two susceptible strains, but overall, vancomycin was the more active
      drug.

PMID- 1399945
TI  - In-vitro activity of RP 59500, a semisynthetic streptogramin, against
      staphylococci and streptococci.
AB  - The in-vitro activity of RP 59500, an injectable streptogramin derived from
      pristinamycin, was determined by agar dilution and compared with that of
      pristinamycin. Two hundred and sixty-one recent clinical isolates of Gram
      positive cocci were tested against both antibiotics. The two compounds displayed
      similar activities. The MIC90s of RP 59500 ranged from 0.5 to 2 mg/L in 114
      strains of Staphylococcus aureus showing various phenotypes of antibiotic
      resistance (penicillin-susceptible; penicillin-resistant and methicillin
      susceptible; methicillin-resistant; erythromycin-resistant, either inducible or
      constitutive; quinolone-resistant). Similar results were obtained with coagulase
      negative staphylococci. RP 59500 was consistently active against streptococci,
      with MIC90s of 0.25, 0.25 and 0.50 mg/L for Streptococcus pyogenes (n = 20),
      Streptococcus agalactiae (n = 20) and Streptococcus pneumoniae (n = 20),
      respectively. Enterococcus faecalis (n = 20) appeared to be notably less
      susceptible (MIC90, 8 mg/L). In view of this consistent activity against all
      staphylococci and streptococci tested, including multiply resistant isolates, RP
      59500 merits further investigation.

PMID- 1399946
TI  - In-vitro antibacterial activity of RP 59500, a semisynthetic streptogramin,
      against Streptococcus pneumoniae.
AB  - The in-vitro activity of the new streptogramin RP 59500 was determined against
      100 strains of Streptococcus pneumoniae. In all, 48 erythromycin-sensitive
      strains and 52 erythromycin-resistant strains were tested by an agar dilution
      method (MIC determination), 20 strains (eight erythromycin-sensitive and 12
      erythromycin-resistant) were tested by a broth microdilution technique (MIC and
      MBC determination) and ten strains (two erythromycin-sensitive and eight
      erythromycin-resistant) were tested for bactericidal kinetics. The study showed
      that RP 59500 had good bacteristatic and bactericidal activity against both
      erythromycin-sensitive and erythromycin-resistant strains. On the basis of these
      results, and because the number of erythromycin-resistant strains of S.
      pneumoniae isolated in France has increased steadily since 1985, RP 59500 might
      be useful for the treatment of pneumococcal infections and warrants further
      investigation.

PMID- 1399947
TI  - The in-vitro activity of RP 59500 against gram-positive cocci.
AB  - RP 59500 was more potent than erythromycin, josamycin, amoxycillin and
      ciprofloxacin, and as potent as vancomycin, against staphylococci and
      enterococci. Against streptococci, the activity of RP 59500 was very similar to
      that of amoxycillin, but was superior to that of erythromycin, josamycin,
      vancomycin or ciprofloxacin. Compared with the other antimicrobial agents tested,
      RP 59500 was the most active against erythromycin-resistant Gram-positive cocci.

PMID- 1399948
TI  - In-vitro activity of RP 59500, a new semisynthetic streptogramin antibiotic,
      against gram-positive bacteria.
AB  - A study of the in-vitro activity of RP 59500, a semisynthetic derivative of
      pristinamycin, against a range of Gram-positive bacteria including erythromycin
      resistant strains was undertaken. MICs were determined by plate dilution in
      IsoSensitest agar and MBCs by velvet pad replication. RP 59500 was found to have
      in-vitro activity almost identical to that of its parent compound, pristinamycin.
      Sixty methicillin-resistant Staphylococcus aureus (MRSA) and 60 methicillin
      sensitive S. aureus (MSSA) were found to be sensitive to RP 59500, with MICs of
      0.13-1 mg/L. All the MSSA and most MRSA showed an MBC less than 2 mg/L.
      Erythromycin-resistant S. aureus (62) were as sensitive to RP 59500 as were
      erythromycin-sensitive strains (58). RP 59500 was more active against MRSA than
      fusidate, vancomycin, amikacin, ciprofloxacin, imipenem or erythromycin. Forty
      strains of coagulase-negative staphylococci (11 were erythromycin-resistant)
      showed MICs of 0.25-1 mg/L, and RP 59500 was more active than methicillin,
      erythromycin, imipenem, cefotaxime or vancomycin. Sixty strains of streptococci
      (20 pneumococci and 40 of groups A, B, C, or G) and 20 enterococci were inhibited
      by 0.13-1 mg/L and 0.25-4 mg/L, respectively. Gram-positive bacilli (five each of
      diphtheroids, lactobacilli, Listeria monocytogenes and Bacillus spp., and 19
      Clostridium spp.) were also sensitive, with MICs of between 0.06 and 4 mg/L. All
      279 strains tested were judged to be sensitive to RP 59500, which was
      bactericidal and showed a small inoculum effect. The activity against MRSA, and
      against erythromycin-resistant strains of all species was particularly
      interesting.

PMID- 1399949
TI  - Comparative in-vitro activity of RP 59500.
AB  - The in-vitro activity of RP 59500 was compared with that of other appropriate
      antibiotics against 131 staphylococci, 97 streptococci, 20 enterococci, 68
      Neisseria spp., 68 Haemophilus influenzae, 21 Moraxella catarrhalis and 250 Gram
      negative bacilli. RP 59500 was more active than oxacillin, vancomycin and
      erythromycin against staphylococci (MIC 0.03-4 mg/L). RP 59500 inhibited
      streptococci between 0.03-1 mg/L and enterococci between 1-8 mg/L, but was less
      active than ampicillin and erythromycin. However, its activity remained unchanged
      against strains with acquired resistance to ampicillin, erythromycin and
      oxacillin. It was as active as ampicillin against Neisseria spp., but less active
      against H. influenzae and M. catarrhalis. All enterobacteria and non-fermenters
      were resistant to RP 59500.

PMID- 1399950
TI  - Comparative in-vitro activity of RP 59500 against clinical bacterial isolates.
AB  - The activity of RP 59500 against Gram-positive cocci was determined by an agar
      dilution method and compared with that of erythromycin, cefotaxime and
      ampicillin. Of the 344 clinical isolates tested, none was resistant to RP 59500;
      this compound was active both against methicillin-resistant Staphylococcus aureus
      and against macrolide-resistant Gram-positive cocci. The bactericidal activity of
      RP 59500 was confirmed by killing curve determinations.

PMID- 1399951
TI  - A collaborative study of the in-vitro sensitivity to RP 59500 of bacteria
      isolated in seven hospitals in France.
AB  - The in-vitro activity of RP 59500 was determined against 1051 recent clinical
      bacterial isolates. The susceptibility to RP 59500 was determined with an agar
      dilution technique for all the isolates, while MICs and MBCs were determined for
      82 selected strains in broth. Isolates of both Staphylococcus aureus and
      coagulase-negative staphylococci appeared to be potentially susceptible to RP
      59500, independent of susceptibility to methicillin or MLS resistance. (S.
      aureus: methicillin-sensitive, MIC90, 1.0 mg/L; methicillin-resistant, MIC90 1.0
      mg/L; coagulase-negative staphylococci: methicillin-sensitive, MIC90 0.5 mg/L).
      Lancefield group A, B, C and G streptococci (MIC50 0.5 and MIC90 1.0 mg/L) and
      Streptococcus pneumoniae (MIC50 0.5 and MIC90 1.0 mg/L) appeared to be
      susceptible to RP 59500. Some Streptococcus spp. and enterococci as well as
      Listeria monocytogenes were inhibited by a higher concentration of RP 59500
      (enterococci: MIC90 4 mg/L, range 0.125-16 mg/L). Comparatively low MICs were
      seen when Legionella spp., Neisseria gonorrhoeae and Gardnerella vaginalis were
      tested. Broth dilution MIC/MBC determinations showed no evidence of tolerance, as
      MIC values were within two dilutions of MBC values. RP 59500 might be a useful
      compound in the treatment of infections caused by a range of Gram-negative and
      Gram-positive bacteria, including those resistant to methicillin and/or
      macrolides.

PMID- 1399952
TI  - In-vitro activity of streptogramin RP 59500 against staphylococci, including
      bactericidal kinetic studies.
AB  - The in-vitro activity of RP 59500 and comparative agents was determined against
      270 clinical isolates of the genus Staphylococcus. MICs were performed by micro
      dilution dilution. MIC90 and MBC90 (mg/L) of RP 59500 were as follows: oxacillin
      sensitive Staphylococcus aureus (0.5/0.5), oxacillin-resistant S. aureus
      (0.5/0.5), oxacillin-sensitive Staphylococcus epidermidis (0.5/0.5), oxacillin
      resistant S. epidermidis (0.25/0.25), oxacillin-resistant Staphylococcus hominis
      (1.0/1.0), oxacillin-resistant Staphylococcus haemolyticus (1.0/1.0), oxacillin
      sensitive Staphylococcus saprophyticus (1.0/1.0). Killing kinetic methods were
      used to assess the bactericidal activity of inhibitory (1 x, 2 x MIC)
      concentrations of RP 59500 in comparison with that of vancomycin (1 x, 2 x MIC)
      and oxacillin (1 x, 2 x MIC) against 20 strains of oxacillin-sensitive and 
      resistant S. aureus and S. epidermidis. RP 59500 was as active as vancomycin,
      displaying rapid bactericidal activity against the majority of strains tested and
      reducing initial inoculum counts by greater than 99.9% in 2-12 h. Regrowth was
      seen with some S. epidermidis strains after 12-24 h.

PMID- 1399953
TI  - Activity of RP 59500, a new parenteral semisynthetic streptogramin, against
      staphylococci with various mechanisms of resistance to macrolide-lincosamide
      streptogramin antibiotics.
AB  - RP 59500 is a semisynthetic streptogramin (Sg) composed of two synergic
      components: RP 57669 and RP 54476. The activities of RP 59500, RP 57669 and RP
      54476 were tested against 20 strains of staphylococci susceptible to macrolide,
      lincosamide and streptogramin antibiotics (MLS) and against strains exhibiting
      different MLS resistance mechanisms. RP 59500 was active against 14 strains
      harbouring emrA or ermC genes which were inducibly or constitutively resistant to
      erythromycin (MICs of 0.5-2 mg/L). Neither RP 59500, RP 57669 nor RP 54476
      induced MLSB resistance. Constitutive mutants appeared at frequencies of 10(-7)
      10(-8) when two MLSB-inducible strains of staphylococci were exposed to 40 mg/L
      each of clindamycin and RP 57669. No such mutants appeared on plates containing
      RP 59500 or RP 54476. The emergence of mutants was prevented if the cultures were
      exposed to RP 54476 (40 mg/L), indicating that such mutants are unlikely to be
      selected in vivo by RP 59500. However, for some constitutive mutants, MBCs of RP
      59500 were as high as 8 mg/L. Strains producing acetyltransferase and hydrolase,
      inactivating SgA- and SgB-type antibiotics respectively, were resistant to RP
      59500, RP 57669 and RP 54476. Production of Pincosamide nucleotidyltransferase-4,
      which inactivates lincosamides, had no effect on the MICs of RP 59500, RP 57669
      and RP 54476.

PMID- 1399954
TI  - In-vitro activity of RP 59500, a new synergic antibacterial agent, against
      Legionella spp.
AB  - The in-vitro activity of RP 59500, a new semisynthetic injectable streptogramin,
      was compared with that of erythromycin, rifampicin and ciprofloxacin against 189
      Legionella spp. Rifampicin was the most active agent tested. RP 59500 was found
      to be more active than erythromycin against most strains, but less active than
      ciprofloxacin. Legionella pneumophila serogroups 1, 3, 4, 5 and 6 were more
      susceptible to RP 59500 than were L. pneumophila serogroups 2, 7, and 8.
      Legionella micdadei was the least susceptible species to RP 59500 and
      erythromycin. RP 59500 was similar in activity against isolates obtained from
      both patients and environmental sources. This activity was generally better than
      that of erythromycin.

PMID- 1399955
TI  - RP 59500: a proposed mechanism for its bactericidal activity.
AB  - RP 59500 is a combination of RP 57669 and RP 54476, which are semisynthetic water
      soluble derivatives of pristinamycin IA (PIA) and pristinamycin IIA (PIIA),
      respectively. Like their precursors, these molecules are bacteristatic in their
      own right. In association, they exert bactericidal activity against a variety of
      Gram-positive bacteria. Experiments involving the binding of these antibiotics to
      the target bacterial ribosome showed that both the binding sites and the
      mechanism of action of the components of RP 59500 are identical to those of the
      parent molecules. By affinity-labelling with a structural analogue of RP 57669,
      it was demonstrated that L24, a protein of the 70S ribosomal subunit, was
      specifically labelled. Experiments using radioactive N-ethylmaleimide to label
      proteins possessing a thiol residue, indicated that proteins L24, L10 and L11 are
      not only close to each other in the ribosomal structure, but are also adjacent
      (if not actually part of) the channel through which newly synthesized proteins
      are extruded. We propose that the mechanism of action of these compounds is to
      close or narrow the extrusion channel of these proteins, which could lead to
      their accumulation on the ribosome. We cannot exclude, of course, the possibility
      that this accumulation disturbs peptidyl-tRNA hydrolase (PHT) activity, thereby
      depleting free tRNAs within the cell and inhibiting protein synthesis.

PMID- 1399956
TI  - In-vitro and in-vivo synergic activity and fractional inhibitory concentration
      (FIC) of the components of a semisynthetic streptogramin, RP 59500.
AB  - RP 59500 is a new semisynthetic injectable streptogramin antibiotic composed of
      two compounds which interact synergically, RP 57669 and RP 54476, derived from
      pristinamycin IA and pristinamycin IIB, respectively. The bacteristatic and
      bactericidal activities of RP 57669 and RP 54476 alone or combined in various
      proportions were tested by the chequerboard dilution technique. The fractional
      inhibitory concentration (FIC) index was determined for 14 Staphylococcus aureus
      isolates (including methicillin- and macrolide-resistant strains) and one culture
      collection strain. The FIC index was found to be much lower than 0.5, indicating
      the presence of synergy for all strains tested, whatever their resistance
      pattern. The ED50 of RP 57669 and RP 54476 in various combinations were also
      determined in three experimental murine models of septicaemia, caused by either
      S. aureus or Streptococcus pneumoniae, and a thigh abscess model caused by S.
      aureus. The combinations which performed best in the model of septicaemia were
      those in which the RP 57669: RP 54476 ratio ranged from 16:84 to 92:8, while
      those active against the thigh abscess model had ratios ranging from 8:92 to
      84:16. That the drugs were active over a wide range of ratios suggests that
      synergy will be maintained even if one drug is cleared more rapidly than the
      other. The combination of 30:70, referred to as RP 59500, was selected for
      further studies, both in vitro and in various experimental models of infections.

PMID- 1399957
TI  - Central neural mechanisms of progesterone action: application to the respiratory
      system.
AB  - Around the turn of the century, it was recognized that women hyperventilate
      during the luteal phase of the menstrual cycle and during pregnancy. Although a
      causative role for the steroid hormone progesterone in this hyperventilation was
      suggested as early as the 1940s, there has been no clear indication as to the
      mechanism by which it produces its respiratory effects. In contrast, much
      mechanistic information has been obtained over the same period about a different
      effect of progesterone, i.e., the facilitation of reproductive behaviors. In this
      case, the bulk of the evidence supports the hypothesis that progesterone acts via
      a genomic mechanism with characteristics not unlike those predicted by classic
      models for steroid hormone action. We recently, therefore, undertook a series of
      experiments to test predictions of those same models with reference to the
      respiratory effects of progesterone. Here we highlight the results of those
      studies; as background to and precedent for our experiments, we briefly review
      previous work in which effects of progesterone on respiration and reproductive
      behaviors have been studied. Our results indicate that the respiratory response
      to progesterone is mediated at hypothalamic sites through an estrogen- (E2)
      dependent progesterone receptor- (PR) mediated mechanism requiring RNA and
      protein synthesis, i.e., gene expression. The E2 dependence of the respiratory
      response to progesterone is likely a consequence of the demonstrated induction of
      PR mRNA and PR in hypothalamic neurons by E2. In short, we found that neural
      mechanisms underlying the stimulation of respiration by progesterone were similar
      to those mediating its reproductive effects.

PMID- 1399958
TI  - Distribution of peripheral blood leukocytes in acute heatstroke.
AB  - We examined 11 heatstroke patients (mean rectal temperature 41.4 +/- 0.3 degrees
      C) and 40 healthy subjects to determine the effects of hyperthermia on peripheral
      blood leukocyte distribution. Precooling samples were taken on admission. Whole
      blood was incubated with conjugated monoclonal antibodies, and erythrocytes were
      eliminated by FACS lysing solution. Lymphocyte subsets were detected by specific
      mouse monoclonal antibodies: Leu-4/CD3+ (T-cells), Leu-3a/CD4+ (T-helper cells),
      Leu-2a/CD8+ (T-suppressor-cytotoxic cells), Leu-11/19/CD16+/CD56+ (natural killer
      cells), and Leu-12/CD19+ (B-cells). Immunofluorescence was measured with a flow
      cytometer. The number of circulating leukocytes and lymphocytes was significantly
      increased in heatstroke patients. This lymphocytosis was mainly due to an
      increase in T-suppressor-cytotoxic cells and natural killer cells. The absolute
      number of lymphocytes and T-suppressor-cytotoxic cells significantly correlated
      with the degree of hyperthermia (r = 0.62, P = 0.04; r = 0.751, P = 0.007,
      respectively). There was a significant decrease in the percentages of T-, B-, and
      T-helper cells and increase in T-suppressor-cytotoxic and natural killer cells,
      giving a marked decrease in the ratio of T-helper to T-suppressor-cytotoxic
      cells. We conclude that heatstroke is associated with leukocytosis and
      significant alteration in absolute number and percentage of circulating
      lymphocyte subpopulations.

PMID- 1399959
TI  - Bronchial provocation tests in small animals: a quantified and automated
      procedure.
AB  - Bronchial provocation tests using aerosols in laboratory animals are difficult to
      standardize and quantify, because the amount of drug actually reaching the
      airways is unknown. To improve the quantification of aerosolized inhaled stimuli,
      we designed an apparatus that allows, in anesthetized intubated ventilated
      animals, control of temperature and hygrometry of inspired air, computerized
      measurement of pulmonary resistance, and fully automated delivery of a known
      amount of aerosolized drug directly into the trachea. Calibration of the aerosol
      delivery involved direct measurement of liquid delivered at the tip of the
      tracheal cannula. Despite all our efforts at standardization and full automation
      of all steps, reproducibility of aerosol delivery was poor, with stroke-by-stroke
      differences of 26 or 42%, according to whether an air-jet or an ultrasonic
      nebulizer was used. Histamine dose-response curves performed in 15 guinea pigs
      with this device confirmed marked differences among animals and also disclosed
      large intraindividual changes in bronchial responsiveness.

PMID- 1399960
TI  - Mental stress and cognitive performance do not increase overall level of cerebral
      O2 uptake in humans.
AB  - We measured cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF),
      and cerebral lactate output during rest, during the execution of mental
      arithmetic, and during mental stress induced by physical and psychological
      annoyance. Measurements were performed in healthy volunteers by use of the Kety
      Schmidt technique with 133Xe as the inert gas. Electroencephalographic
      desynchronization and highly significant increases in plasma catecholamines and
      heart rate verified that the test measurements were performed during conditions
      differing distinctly from the resting state. In accordance with an earlier study
      (Sokoloff et al. J. Clin. Invest. 34: 1101-1108, 1985), a minimal and
      nonsignificant 1% reduction of global CMRO2 during mental arithmetic was
      observed, signifying that this form of mental activation was unassociated with
      any detectable increase in overall cerebral synaptic activity. Mental stress
      induced a slight but highly significant (P less than 0.002) 6% reduction in
      global CMRO2. This finding is in contrast to results from earlier investigations
      and contradicts the generally accepted notion of an association between mental
      arousal and a diffuse upregulation of cerebral synaptic activity. During mental
      arithmetic and mental stress, cerebral lactate output increased by 207 and 344%,
      respectively, but because of large individual variations in the measured
      responses, the elevations reached statistical significance only during mental
      arithmetic.

PMID- 1399961
TI  - Mechanical impedances of lungs and chest wall in the cat.
AB  - In nine anesthetized and paralyzed cats, the mechanical impedances of the total
      respiratory system (Zrs) and the lungs (ZL) were measured with small-volume
      pseudorandom forced oscillations between 0.2 and 20 Hz. ZL was measured after
      thoracotomy, and chest wall impedance (Zw) was calculated as Zw = Zrs-ZL. All
      impedances were determined by using input airflow [input impedance (Zi)] and
      output flow measured with a body box [transfer impedance (Zt)]. The differences
      between Zi and Zt were small for Zrs and negligible for ZL. At 0.2 Hz, the real
      and imaginary parts of ZL amounted to 33 +/- 4 and 35 +/- 3% (SD), respectively,
      of Zrs. Up to 8 Hz, all impedances were consistent with a model containing a
      frequency-independent resistance and inertance and a constant-phase tissue part
      (G-jH)/omega alpha, where G and H are coefficients for damping and elastance,
      respectively, omega is angular frequency, and alpha determines the frequency
      dependence of the real and imaginary parts. G/H was higher for Zw than for ZL
      (0.29 +/- 0.05 vs. 0.22 +/- 0.04, P less than 0.01). In four cats, the amplitude
      dependence of impedances was studied: between oscillation volumes of 0.8 and 3
      ml, GL, HL, Gw, and Hw decreased on average by 3, 9, 26, and 29%, respectively,
      whereas the change in G/H was small for both ZL (7%) and Zw (-4%). The values of
      H were two to three times higher than the quasistatic elastances estimated with
      greater volume changes (greater than 20 ml).

PMID- 1399962
TI  - Effect of volume history on changes in DLcoSB-3EQ with lung volume in normal
      subjects.
AB  - The purpose of this study was to determine the relationship between the three
      equation diffusing capacity for carbon monoxide (DLcoSB-3EQ) and lung volume and
      to determine how this relationship was altered when maneuvers were immediately
      preceded by a deep breath. DLcoSB-3EQ maneuvers were performed in nine healthy
      subjects either immediately after a deep breath or after tidal breathing for 10
      min. The maneuvers consisted of slow inhalation of test gas from functional
      residual capacity to 25, 50, 75, or 100% of the inspiratory capacity and, without
      breath holding, slow exhalation to residual volume. After either a deep breath or
      tidal breathing, we found that DLcoSB-3EQ decreased nonlinearly with decreasing
      lung volume. At all lung volumes, DLcoSB-3EQ was significantly greater when
      measured after a deep breath than after tidal breathing. This effect increased as
      lung volume decreased, so that the greatest difference between DLcoSB-3EQ after a
      deep breath and that after tidal breathing occurred at the lowest lung volume. We
      conclude that a deep breath or spontaneous sigh has a role in reestablishing the
      pathway for gas exchange during tidal breathing.

PMID- 1399963
TI  - Effort sensation, chemoresponsiveness, and breathing pattern during inspiratory
      resistive loading.
AB  - Although inspiratory resistive loading (IRL) reduces the ventilatory response to
      CO2 (VE/PCO2) and increases the sensation of inspiratory effort (IES), there are
      few data about the converse situation: whether CO2 responsiveness influences
      sustained load compensation and whether awareness of respiratory effort modifies
      this behavior. We studied 12 normal men during CO2 rebreathing while free
      breathing and with a 10-cmH2O.l-1.s IRL and compared these data with 5 min of
      resting breathing with and without the IRL. Breathing pattern, end-tidal PCO2,
      IES, and mouth occlusion pressure (P0.1) were recorded. Free-breathing VE/PCO2
      was inversely related to an index of effort perception (IES/VE; r = -0.63, P less
      than 0.05), and the reduction in VE/PCO2 produced by IRL was related to the
      initial free-breathing VE/PCO2 (r = 0.87, P less than 0.01). IRL produced
      variable increases in inspiratory duration (TI), IES, and P0.1 at rest, and the
      change in tidal volume correlated with both VE/PCO2 (r = 0.63, P less than 0.05)
      and IES/VE (r = -0.69, P less than 0.05), this latter index also predicting the
      changes in TI with loading (r = -0.83, P less than 0.01). These data suggest that
      in normal subjects perception of inspiratory effort can modify free-breathing CO2
      responsiveness and is as important as CO2 sensitivity in determining the response
      to short-term resistive loading. Individuals with good perception choose a small
      tidal volume and short-TI breathing pattern during loading, possibly to minimize
      the discomfort of breathing.

PMID- 1399964
TI  - A comparative study of postpneumonectomy compensatory lung response in growing
      male and female rats.
AB  - Postpneumonectomy compensatory lung response and normal lung growth in the early
      postnatal period were studied in male and female rats. Four-week-old litter
      matched male and female Sprague-Dawley rats were subjected to left pneumonectomy
      or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung
      weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number
      (N(at)), and the amount of DNA and protein increased significantly. In both males
      and females, WL, VL, and Sw matched those of both lungs of the sham-operated
      group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy
      and sham-operated rats were smaller in body weight than males. Absolute WL, VL,
      Sw, N(at), and the amount of DNA and protein were significantly lower, but
      specific parameters (per unit body weight) were significantly greater in females
      than in males. After pneumonectomy, the postcaval lobe increased most in volume
      (70 and 73% in males and females, respectively). Mean linear intercept and mean
      chord length of alveoli increased, and the number of alveoli per unit volume
      decreased more in the postcaval and middle lobes than in upper and lower lobes in
      both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in
      females. We conclude that, in certain aspects (WL, VL), compensatory growth
      matched both lungs of controls, but in others (biochemical, morphometric) it did
      not. There was evidence of alveolar multiplication, but the dominant effect was
      enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399965
TI  - Endurance training of older men: responses to submaximal exercise.
AB  - The purpose of this study was to quantify the exercise response of older subjects
      on a time-to-fatigue (TTF) submaximal performance test before and after a
      training program. Eight older men (67.4 +/- 4.8 yr) performed two maximal
      treadmill tests to determine maximum oxygen uptake (VO2max) and ventilation
      threshold (TVE) and a constant-load submaximal exercise treadmill test that
      required an oxygen uptake (VO2) between TVE and VO2max. The submaximal test,
      performed at the same absolute work rate before and after the training program,
      was performed to volitional fatigue to measure endurance time. The men trained
      under supervision at an individualized pace representing approximately 70% of
      VO2max (80% maximum heart rate) for 1 h, four times per week for 9 wk.
      Significant increases were demonstrated for VO2max (ml.kg-1.min-1; 10.6%);
      maximal ventilation (VE, l/min; 11.6%), and TVE (l/min; 9.8%). Weight decreased
      2.1%. Performance time on the TTF test increased by 180% (7.3 +/- 3.0 to 20.4 +/-
      13.5 min). The similar end points for VO2, VE, and heart rate during the TTF and
      maximal treadmill tests established that the TTF test was stopped because of
      physiological limitations. The increase in performance time among the subjects
      was significantly correlated with improvements in VO2max and TVE, with the
      submaximal work rate representing a VO2 above TVE by 88% of the difference
      between TVE and VO2max pretraining and 73% of this difference on posttraining
      values.

PMID- 1399966
TI  - Ontogeny of integumental calcium in relation to surface area and skin water
      content in the perinatal rat.
AB  - Calcium is an important regulator of epidermal differentiation and skin
      biomechanics in many vertebrate species. In this study, we measured total
      epidermal calcium in the perinatal Sprague-Dawley rat. Values ranged from 12 to
      15 mg per 100 g of tissue. These levels were elevated compared with dermis and
      other soft (nonbone) organs, including brain, kidney, heart, and liver.
      Administration of radioactive calcium to the pregnant rat resulted in high rates
      of 45Ca2+ localization in the fetal epidermis 24 h later. From gestational day 20
      to postnatal day 3, the epidermis showed progressive dehydration with water
      content decreasing from 79 to 73%. Dermal hydration over the same period
      decreased from 91 to 81%. In the neonatal rat (age 0-3 days), linear regression
      analysis of surface area vs. body weight on a log-log plot yielded a slope of
      1.04. This finding contrasts with an expected slope of 0.67 based on simple
      surface area-to-volume relationships and differs from the empirical 0.75-power
      law observed in adult bioenergetics. In summary, these results show the perinatal
      rat is encapsulated by a continuous differentially hydrated calcium-rich
      epidermal envelope that increases in surface area over the early postnatal period
      directly as the first power of body mass.

PMID- 1399967
TI  - Changes in respiratory muscle activity in conscious cats during experimental
      dives at 101 ATA.
AB  - The rationale for the present study was to test the hypothesis that increased
      work of breathing during experimental deep diving may lead to respiratory muscle
      fatigue. For this purpose, electromyograms (EMGs) of respiratory and skeletal
      muscles, plus electrocardiogram and electroencephalogram (EEG) derivatives, were
      continuously recorded in conscious cats. In each muscle group, the ratio of power
      in a high (H) to that in a low (L) band of EMG frequencies was computed. Direct
      diaphragmatic stimulation in selected animals produced a mass action potential to
      obtain the muscle fiber conduction velocity (MFCV). The maximal pressure was 101
      ATA (1,000 msw) with a maximal duration of 72 h. Four cats breathed an He-O2
      mixture and five others a ternary mixture (10% N2 in He-O2). Inspired O2 partial
      pressure was 350 Torr. With the He-O2 mixture, all the animals died within 2-54 h
      during the study at maximal depth. EEG signs of high-pressure nervous syndrome
      (HPNS) were present in all cats, and low-frequency (11-14 Hz) hyperbaric tremor
      discontinuously contaminated all EMG tracings. The H/L ratio computed from
      diaphragmatic and intercostal muscle EMGs increased after 12 h at 101 ATA. With
      the He-N2-O2 mixture, the cats survived until the end of the sojourn at 101 ATA,
      during which no hyperbaric tremor was detected from EMG tracings, and EEG signs
      of HPNS were weak or absent. From 31 ATA, the H/L ratio decreased significantly
      in respiratory but not in skeletal muscles; this was associated with decreased
      MFCV in the diaphragm after several hours at maximal depth.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1399968
TI  - Pulmonary vasodilatory response to neurohypophyseal peptides in the rat.
AB  - Experiments were performed on isolated salt-perfused rat lungs to determine the
      receptor type(s) responsible for the pulmonary vascular effects of the
      neurohypophyseal peptides arginine vasopressin (AVP) and oxytocin. Bolus
      administration of AVP to lungs preconstricted with the thromboxane mimetic U
      46619 resulted in a dose-dependent vasodilatory response (approximately 65%
      reversal of U-46619-induced vasoconstriction at the highest dose tested) that was
      blocked by pretreatment with a selective V1- but not by a selective V2
      vasopressinergic receptor antagonist. Administration of a selective V1-agonist to
      the preconstricted pulmonary vasculature resulted in a vasodilatory response
      similar to that observed with AVP (approximately 55% reversal of U-46619
      vasoconstriction), which was blocked by prior administration of the selective V1
      receptor antagonist. Administration of the selective V2-receptor agonist
      desmopressin to the preconstricted pulmonary vasculature resulted in a small
      (approximately 8% reversal of U-46619 vasoconstriction) vasodilatory response
      that was, nevertheless, greater than that produced by addition of vehicle alone
      and was attenuated by pretreatment with a selective V2-receptor antagonist.
      Finally, oxytocin also caused vasodilation in the preconstricted pulmonary
      vasculature; however, the potency of oxytocin was approximately 1% of AVP, and
      the vasodilation produced by oxytocin was blocked by prior administration of a
      selective V1-receptor antagonist, suggesting that oxytocin acts via V1
      vasopressinergic receptor stimulation. We conclude from these experiments that
      AVP and oxytocin dilate the preconstricted pulmonary vasculature primarily via
      stimulation of V1-vasopressinergic receptors. V2-receptor stimulation results in
      a minor vasodilatory response, although its physiological significance is
      unclear.

PMID- 1399969
TI  - Intrinsic PEEP monitored in the ventilated ARDS patient with a mathematical
      method.
AB  - Under mechanical volume-controlled ventilation, the intensive care patient can
      develop intrinsic positive end-expiratory pressure (iPEEP); that is, the passive
      expiration is terminated by the following inspiration before the alveolar
      pressure comes to its physical equilibrium value. We present a mathematical
      method to estimate this alveolar dynamic iPEEP breath by breath, without the need
      of a maneuver. We tested it in paralyzed patients ventilated for adult
      respiratory distress syndrome after multiple trauma and/or sepsis, and we
      compared the results obtained with the new mathematical method with those from
      the occlusion method introduced by Pepe and Marini. The results agreed well
      (median difference of 0.8 mbar in 201 investigations in 12 patients). However,
      the mathematically determined values, representing dynamic iPEEP, are
      systematically slightly smaller than those measured by the occlusion maneuver. A
      variation of expiratory time suggests that this difference might be due to
      mechanical time-constant inhomogeneity, viscoelastic processes, or other
      mechanisms showing time dependence.

PMID- 1399970
TI  - Glucose transporters and maximal transport are increased in endurance-trained rat
      soleus.
AB  - Voluntary wheel running induces an increase in the concentration of the
      regulatable glucose transporter (GLUT4) in rat plantaris muscle but not in soleus
      muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes
      39: 1425-1429, 1990). Wheel running also causes hypertrophy of the soleus in
      rats. This study was undertaken to ascertain whether endurance training that
      induces enzymatic adaptations but no hypertrophy results in an increase in the
      concentration of GLUT4 protein in rat soleus (slow-twitch red) muscle and, if it
      does, to determine whether there is a concomitant increase in maximal glucose
      transport activity. Female rats were trained by treadmill running at 25 m/min up
      a 15% grade, 90 min/day, 6 days/wk for 3 wk. This training program induced
      increases of 52% in citrate synthase activity, 66% in hexokinase activity, and
      47% in immunoreactive GLUT4 protein concentration in soleus muscles without
      causing hypertrophy. Glucose transport activity stimulated maximally with insulin
      plus contractile activity was increased to roughly the same extent (44%) as GLUT4
      protein content in soleus muscle by the treadmill exercise training. In a second
      set of experiments, we examined whether a swim-training program increases glucose
      transport activity in the soleus in the presence of a maximally effective
      concentration of insulin. The swimming program induced a 44% increase in
      immunoreactive GLUT4 protein concentration. Glucose transport activity maximally
      stimulated with insulin was 62% greater in soleus muscle of the swimmers than in
      untrained controls. Training did not alter the basal rate of 2-deoxyglucose
      uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399972
TI  - Effects of systolic and diastolic positive pleural pressure pulses with altered
      cardiac contractility.
AB  - Positive pleural pressure (Ppl) decreases left ventricular afterload and preload.
      The resulting change in cardiac output (CO) in response to these altered loading
      conditions varies with the baseline level of cardiac contractility. In an
      isolated canine heart-lung preparation, we studied the effects of positive Ppl
      applied phasically during systole or diastole on CO and on the cardiac function
      curve (the relationship between CO and left atrial transmural pressure). When
      baseline cardiac contractility was enhanced by epinephrine infusion, systolic and
      diastolic positive Ppl decreased CO equally (1,931 +/- 131 to 1,419 +/- 124 and
      1,970 +/- 139 to 1,468 +/- 139 ml/min, P less than 0.01) and decreased the
      pressure gradient driving venous return. However, neither shifted the position of
      the cardiac function curve, suggesting that the predominant effect of positive
      Ppl was decreased preload. When baseline cardiac contractility was depressed by
      severe respiratory acidosis, diastolic positive Ppl pulses caused no significant
      change in CO (418 +/- 66 to 386 +/- 52 ml/min), the cardiac function curve, or
      the pressure gradient for venous return. However, systolic positive Ppl pulses
      increased CO from 415 +/- 70 to 483 +/- 65 ml/min (P less than 0.01) and
      significantly shifted the cardiac function curve to the left. Thus the effect of
      Ppl pulsations on CO works through different mechanisms, depending on the state
      of cardiac contractility.

PMID- 1399973
TI  - Regional differences in myosin heavy chain isoforms and enzyme activities of the
      rat diaphragm.
AB  - Myosin heavy chain isoforms and enzyme activities were compared between the
      costal and crural regions of the rat diaphragm. The percentage of heavy chain
      (HC) IIb in the crural region of the diaphragm was significantly (P less than
      0.05) higher than that in the costal region (mean 7.3 vs. 3.0%), and the
      percentage of HCI was significantly lower in the crural than in the costal
      diaphragm (22.7 vs. 27.9%). The distributions of HCIIa and HCIId were relatively
      homogeneous in both regions. Succinate dehydrogenase activity in the costal
      diaphragm was 21% greater (P less than 0.01) than in the crural diaphragm. In
      contrast, there was no significant difference in the activity of
      phosphofructokinase in the crural and costal diaphragms. These results
      demonstrate that a difference in myosin heavy chain isoforms and oxidative
      capacity exists between the costal and crural regions of the rat diaphragm.

PMID- 1399971
TI  - Altered distribution of mitochondria in rat soleus muscle fibers after
      spaceflight.
AB  - The influence of spaceflight on the distribution of succinate dehydrogenase (SDH)
      activity throughout the cross section of fibers in the soleus was studied in five
      male rats and in five rats maintained under ground-based simulated flight
      conditions (control). The flight (COSMOS 1887) was 12.5 days in duration, and the
      animals were killed approximately 2 days after return to 1 G. Fibers were
      classified as slow-twitch oxidative or fast-twitch oxidative-glycolytic in
      histochemically prepared tissue sections. The distribution of SDH activity
      throughout the cross section of 20-30 fibers (each type) was determined using
      quantitative histochemical and computer-assisted image analysis techniques. In
      all the fibers, the distribution of SDH activity was significantly higher in the
      subsarcolemmal than in intermyofibrillar region. After spaceflight the entire
      regional distribution of SDH activity was significantly altered in the slow
      twitch oxidative fibers. The fast-twitch oxidative-glycolytic fibers of the
      spaceflight muscles exhibited a significantly lower SDH activity only in their
      subsarcolemmal region. These data suggest that when determining the influence of
      spaceflight on muscle fiber oxidative metabolism enzymes, it is important to
      consider the location of the enzyme throughout the cross section of a fiber.
      Furthermore the functional properties of the soleus that depend on the metabolic
      support of mitochondria in the subsarcolemmal region may be primarily affected by
      exposure to microgravity.

PMID- 1399974
TI  - Hepatic adaptations to iron deficiency and exercise training.
AB  - Brooks et al. [Am. J. Physiol. 253 (Endocrinol. Metab. 16): E461-E466, 1987]
      demonstrated an elevated gluconeogenic rate in resting iron-deficient rats.
      Because physical exercise also imposes demand on this hepatic function, we
      hypothesized that exercise training superimposed on iron deficiency would augment
      the hepatic capacity for amino acid transamination/deamination and pyruvate
      carboxylation. Sprague-Dawley rats (n = 32) were obtained at weaning (21 days of
      age) and randomly assigned to iron-sufficient (dietary iron = 60 mg iron/kg diet)
      or iron-deficient (3 mg iron/kg) dietary groups. Dietary groups were subdivided
      into sedentary and trained subgroups. Treadmill training was 4 wk in duration, 6
      days/wk, 1 h/day, 0% grade. Treadmill speed was initially 26.8 m/min and was
      decreased to 14.3 m/min over the 4-wk training period. The mild exercise-training
      regimen did not affect any measured variable in iron-sufficient rats. In
      contrast, in iron-deficient animals, training increased endurance capacity
      threefold and reduced blood lactate and the lactate-to-alanine ratio during
      submaximal exercise by 34 and 27%, respectively. The mitochondrial oxidative
      capacity of gastrocnemius muscle was increased 46% by training. However, the
      oxidative capacity of liver was not affected by either iron deficiency or
      training. Maximal rates of pyruvate carboxylation and glutamine metabolism by
      isolated liver mitochondria were also evaluated. Iron deficiency and training
      interacted to increase pyruvate carboxylation by intact mitochondria. Glutamine
      metabolism was increased roughly threefold by iron deficiency alone, and training
      amplified this effect to a ninefold increase over iron-sufficient
      animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399975
TI  - Effects of series compliance on twitches superimposed on voluntary contractions.
AB  - The activation of skeletal muscle during voluntary isometric contraction has been
      assessed by measuring the increase in force caused by a superimposed maximal
      shock to the motor nerve (the twitch-interpolation technique). When the muscle is
      held isometric, the increase in force with stimulation (superimposed twitch
      force) decreases with increasing voluntary force, and a line fit through the data
      can be extrapolated to maximal voluntary force at the zero twitch force axis. In
      a previous paper we questioned the applicability of this technique in situations
      where a high series compliance allows the muscle to shorten during the
      superimposed twitch. To explore effects of series compliance, we measured force
      of the adductor pollicis during voluntary isometric contractions with
      noncompliant and compliant loading devices. With the compliant loading device,
      superimposed twitch force was systematically less than with the noncompliant
      device, and the plot of superimposed twitch force vs. voluntary force was often
      concave upward, preventing easy extrapolation to maximal voluntary force. These
      findings are consistent with force-velocity characteristics of muscle and suggest
      that twitch-interpolation data must be interpreted with caution when the muscle
      is not held isometric during the superimposed twitch.

PMID- 1399976
TI  - Mechanical properties of small airways in excised pony lungs.
AB  - We evaluated the pressure-flow relationships in collaterally ventilating segments
      of excised pony lungs by infusing N2, He, Ne, or SF6 at known flows (V) through a
      catheter wedged in a peripheral airway. Measurements were made at segment- (Ps)
      to-airway opening (Pao) pressure differentials of 3-15 cmH2O when the lungs were
      held at transpulmonary pressures of 5, 10, and 15 cmH2O. The data were analyzed
      both by calculating collateral resistance (Ps-Pao/V) and by constructing Moody
      type plots of normalized pressure drop [(Ps-Pao)/(1/2 rho U2, where rho is
      density and U is velocity)] against Reynolds number to assess the pattern of flow
      through the segment and the change in dimension of the flow channels as Ps and
      Pao were changed. The interpretations from these analyses were compared with
      radiographic measurements of the diameters of small airways within the
      collaterally ventilating lung segment at similar pressures. Collateral resistance
      increased as Ps-Pao increased at high Reynolds numbers, i.e., high flows or dense
      gas (SF6). Analysis of the Moody-type plots revealed that flow was density
      dependent at Reynolds number greater than 100, which frequently occurred when N2
      was the inflow gas. The radiographic data revealed that small airway diameter
      increased as Ps-Pao increased at all lung volumes. In addition, at 5 cmH2O Pao,
      small-airway diameter was smaller for a given Ps in the nonhomogeneous case (Ps
      greater than Pao) than small-airway diameter for the same Ps in the homogeneous
      case (Ps = Pao). We interpret these data to suggest that the surrounding lung
      prevented the segment from expanding in the nonhomogeneous case.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1399978
TI  - Plasma volume, fluid shifts, and renal responses in humans during 12 h of head
      out water immersion.
AB  - Changes in plasma volume (PV) throughout 12 h of thermoneutral (34.5 degrees C)
      water immersion (WI) were evaluated in eight subjects by an improved Evans blue
      (EB) technique and by measurements of hematocrit (Hct), hemoglobin (Hb), and
      plasma protein concentrations (Pprot). Appropriate time control studies (n = 6)
      showed no measurable change in PV. At 30 min of immersion, EB measurements
      demonstrated an increase in PV of 16 +/- 2% (457 +/- 70 ml). Calculations,
      however, based on concomitant changes in Hct, Hb, and Pprot showed an increase in
      PV of only 6.9 +/- 0.9 to 10.0 +/- 0.8% at 30 min of WI. PV values based on EB
      measurements subsequently declined throughout WI to (but not below) the
      preimmersion level. Concomitantly, changes in PV calculated from Pprot values
      remained increased, whereas estimations of changes in PV based on Hct and Hb
      values returned to prestudy levels after 4 h of immersion. It is concluded that
      PV initially increases by 16 +/- 2% during WI and does not decline below
      preimmersion and control levels during 12 h of immersion despite a loss of 0.9 +/
      0.2 liter of body fluid. Furthermore, changes in Hct, Hb, and Pprot do not
      provide accurate measures of the changes in PV during WI in humans.

PMID- 1399977
TI  - Circulation, kidney function, and volume-regulating hormones during prolonged
      water immersion in humans.
AB  - To investigate whether prolonged water immersion (WI) results in reduction of
      central blood volume and attenuation of renal fluid and electrolyte excretion,
      these variables were measured in connection with 12 h of immersion. On separate
      days, nine healthy males were investigated before, during, and after 12 h of WI
      to the neck or during appropriate control conditions. Central venous pressure,
      stroke volume, renal sodium (UNaV) and fluid excretion increased on initiation of
      WI and thereafter gradually declined but were still elevated compared with
      control values at the 12th h of WI. Atrial natriuretic peptide (ANP)
      concentration in plasma initially increased threefold during WI and thereafter
      declined to preimmersion levels, whereas plasma renin activity, plasma
      aldosterone, and norepinephrine remained constantly suppressed. It is concluded
      that, compared with the initial increases, central blood volume (central venous
      pressure and stroke volume) is reduced during prolonged WI and renal fluid and
      electrolyte excretion is attenuated. UNaV is still increased at the 12th h of WI,
      whereas renal water excretion returns to control values within 7 h. The WI
      induced changes in ANP, plasma renin activity, plasma aldosterone, and
      norepinephrine may all contribute to the initial increase in UNaV. The results
      suggest, however, that the attenuation of UNaV during the later stages of WI is
      due to the decrease in ANP release.

PMID- 1399979
TI  - Static lung-lung interactions in unilateral emphysema.
AB  - Motivated by the introduction of single-lung transplantation into clinical
      practice, we compared the static mechanical properties of the respiratory system
      in six supine dogs before (at baseline) with those after the induction of
      unilateral emphysema. Relaxation volume (Vrel), total lung capacity (TLC), and
      static compliance of the emphysematous lung increased to 214 +/- 68, 186 +/- 39,
      and 253 +/- 95% (SD) of baseline, respectively. Vrel of the nonemphysematous lung
      fell to 81 +/- 28% of baseline, with no significant change in TLC of the
      nonemphysematous lung or its pressure-volume relationship, indicating that
      unilateral hyperinflation does not cause dropout of contralateral lung units.
      After unilateral emphysema, the chest wall shifted to a higher unstressed or
      neutral volume (when pleural pressure equals atmospheric pressure) in three of
      six animals, minimizing the anticipated decrease in lung recoil pressure at the
      higher respiratory system Vrel. The pattern of relative lung emptying in the
      intact dog and in the excised lungs was similar during stepwise deflations from
      TLC, suggesting that mean pleural pressure of the hemithoraces is equal. We
      conclude that in the dog the static volume distribution between emphysematous and
      nonemphysematous lungs is determined only by differences in lung recoil and
      compliance.

PMID- 1399980
TI  - Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of
      newborn pigs.
AB  - The purpose of this study was to determine whether pulmonary venous pressure
      increases during alveolar hypoxia in lungs of newborn pigs. We isolated and
      perfused with blood the lungs from seven newborn pigs, 6-7 days old. We
      maintained blood flow constant at 50 ml.min-1.kg-1 and continuously monitored
      pulmonary arterial and left atrial pressures. Using the micropuncture technique,
      we measured pressures in 10 to 60-microns-diam venules during inflation with
      normoxic (21% O2-69-74% N2-5-10% CO2) and hypoxic (90-95% N2-5-10% CO2) gas
      mixtures. PO2 was 142 +/- 21 Torr during normoxia and 20 +/- 4 Torr during
      hypoxia. During micropuncture we inflated the lungs to a constant airway pressure
      of 5 cmH2O and kept left atrial pressure greater than airway pressure (zone 3).
      During hypoxia, pulmonary arterial pressure increased by 69 +/- 24% and pressure
      in small venules increased by 40 +/- 23%. These results are similar to those
      obtained with newborn lambs and ferrets but differ from results with newborn
      rabbits. The site of hypoxic vasoconstriction in newborn lungs is species
      dependent.

PMID- 1399981
TI  - Effect of phrenic afferent stimulation on pattern of respiratory muscle
      activation.
AB  - Ventilation and electromyogram (EMG) activities of the right hemidiaphragm,
      parasternal intercostal, triangularis sterni, transversus abdominis,
      genioglossus, and alae nasi muscles were measured before and during central
      stimulation of the left thoracic phrenic nerve in 10 alpha-chloralose
      anesthetized vagotomized dogs. Pressure in the carotid sinuses was fixed to
      maintain baroreflex activity constant. The nerve was stimulated for 1 min with a
      frequency of 40 Hz and stimulus duration of 1 ms at voltages of 5, 10, 20, and 30
      times twitch threshold (TT). At five times TT, no change in ventilation or EMG
      activity occurred. At 10 times TT, neither tidal volume nor breathing frequency
      increased sufficiently to reach statistical significance, although the change in
      their product (minute ventilation) was significant (P less than 0.05). At 20 and
      30 times TT, increases in both breathing frequency and tidal volume were
      significant. At these stimulus intensities, the increases in ventilation were
      accompanied by approximately equal increases in the activity of the diaphragm,
      parasternal, and alae nasi muscles. The increase in genioglossus activity was
      much greater than that of the other inspiratory muscles. Phrenic nerve
      stimulation also elicited inhomogeneous activation of the expiratory muscles. The
      transversus abdominis activity increased significantly at intensities from 10 to
      30 times TT, whereas the activity of the triangularis sterni remained unchanged.
      The high stimulation intensities required suggest that the activation of afferent
      fiber groups III and IV is involved in the response. We conclude that thin-fiber
      phrenic afferent activation exerts a nonuniform effect on the upper airway, rib
      cage, and abdominal muscles and may play a role in the control of respiratory
      muscle recruitment.

PMID- 1399982
TI  - Reactive oxygen species and elastase mediate lung permeability after acid
      aspiration.
AB  - Acid aspiration leads to increased neutrophil (PMN) oxidative metabolism, an
      event associated with lung leukosequestration and permeability increase.
      Neutropenia protected the vascular barrier function against acid injury. This
      study tests whether active oxygen species and elastase (which are presumably
      released by adherent PMNs) affect the microvascular barrier. Anesthetized rats
      underwent tracheostomy and insertion of a cannula into a lung segment. This was
      followed by localized instillation of 0.1 N HCl (n = 18) or saline (n = 18).
      Sequestration of PMNs in acid-aspirated and nonaspirated segments was 77 and 46
      PMNs/high-power field (HPF), respectively, which was higher than control values
      of 11 and 8 PMNs/10 HPF in saline-aspirated and nonaspirated regions (P less than
      0.05). Acid aspiration was associated with increased protein concentration in
      bronchoalveolar lavage (BAL) fluid to 3,550 and 2,900 micrograms/ml in the
      aspirated and nonaspirated lungs, respectively, which were higher than control
      values of 420 and 400 micrograms/ml (P less than 0.05). Acid aspiration also led
      to increased lung wet-to-dry weight ratios (W/D) of 6.6 and 5.4, which were
      higher than control values of 3.4 and 3.3 (P less than 0.05). Intravenous
      treatment of rats (n = 18) 90 min after aspiration with scavengers of reactive
      oxygen species, superoxide dismutase (1,500 U/kg), and catalase (5,000 U/kg),
      both conjugated to polyethylene glycol, did not reduce PMN sequestration but
      attenuated acid aspiration-induced increase in protein accumulation in BAL fluid
      in the aspirated and nonaspirated segments (990 and 610 micrograms/ml) as well as
      the increased lung W/D (4.6 and 4.0; all P less than 0.05).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1399983
TI  - Analysis of pharyngeal resistance and genioglossal EMG activity using a model of
      orifice flow.
AB  - A model of orifice flow has been used to analyze the relationships among
      pressure, flow, and genioglossal electromyographic activity in the human pharynx
      during inspiration. The orifice flow model permits one to assess the character of
      airflow (laminar or turbulent) and to estimate the cross-sectional area of the
      orifice from pressure and flow measurements. On the basis of other data (J. Appl.
      Physiol. 73: 584-590, 1992), this analysis suggests that pharyngeal airflow is
      turbulent. Furthermore the area of the pharynx appears to increase as flow
      increases, but the actual change in pharyngeal diameter necessary to fit the
      pressure-flow data is quite small (0.11-0.87 cm, depending on the assumptions in
      the model). The flow-related increase in orifice area can be attributed, in part,
      to the activation of the genioglossus muscle. However, other flow-related factors
      may also contribute to pharyngeal dilation as airflow increases. Different airway
      shapes (circular and elliptical) and orientations (major axis anteroposterior and
      lateral) were incorporated into the model calculations; these factors modify
      considerably the apparent efficiency of genioglossal electromyographic activity.
      Genioglossal muscle shortening increases pharyngeal area and reduces pharyngeal
      resistance more effectively when the pharynx is elliptical, with the long axis of
      the ellipse oriented laterally. Hence the genioglossus may operate at a
      significant mechanical disadvantage in those patients with obstructive sleep
      apnea with a small sagittally oriented pharyngeal lumen.

PMID- 1399984
TI  - Dependence of pharyngeal resistance on genioglossal EMG activity, nasal
      resistance, and airflow.
AB  - We investigated the quantitative relationships among pharyngeal resistance (Rph),
      genioglossal electromyographic (EMGge) activity, nasal resistance (Rna), and
      airflow in 11 normal men aged 19-50 while they were awake. We made measurements
      with subjects seated with the head erect, seated with the head flexed forward
      approximately 40 degrees, and supine. Each subject wore a face mask connected to
      a pneumotachograph to measure airflow. After topical anesthesia of the nose, two
      catheters for measuring nasal and pharyngeal airway pressures were passed through
      one nostril: the nasal pressure catheter was positioned at the nasal choanae, and
      the pharyngeal pressure catheter was positioned just above the epiglottis. We
      measured EMGge activity with an intraoral surface electrode. The subjects
      breathed exclusively through the nose while inhaling room air or rebreathing CO2.
      We measured Rph, Rna, airflow, and EMGge activity at approximately 90-ms
      intervals throughout each inspiration. Rph was invariant as head position was
      changed. At any given head position, EMGge activity rose as airflow increased,
      and Rph remained constant. In contrast, Rna increased as airflow increased.
      Because Rph was constant, EMGge activity was not correlated with Rph, but EMGge
      was positively correlated with Rna and airflow. On the basis of the stability of
      Rph in the face of marked changes in collapsing forces, we conclude that the
      dynamic interplay of posture, head and jaw position, and upper airway muscle
      activity quite effectively maintains pharyngeal patency, and interactions among
      these factors are subtle and complex.

PMID- 1399985
TI  - Potentiation of exercise ventilatory response by airway CO2 and dead space
      loading.
AB  - We examined the effects of different modes of airway CO2 load on the ventilation
      CO2 output (VE-VCO2) relationship during mild to moderate exercise. Four young
      and three older male subjects underwent incremental steady-state treadmill
      exercise while breathing a mixture of CO2 in O2 (CO2 loading) or 100% O2 with and
      without a large external dead space [DS loading and control (C), respectively].
      During DS loading, the elevated arterial PCO2 (PaCO2) remained constant from rest
      to mild exercise and began to increase only at higher work rates. To achieve
      similar chemical drive, the same PaCO2 levels were established during CO2 loading
      by external PCO2 forcing. In the young group, CO2 loading resulted in a
      steepening of the VE-VCO2 relationship compared with C, whereas in the older
      group the reverse pattern was found. DS loading resulted in a consistent increase
      in the VE-VCO2 slope compared with C and CO2 loading [39.1 +/- 5.6 (mean +/- SD)
      vs. 24.9 +/- 5.0 and 26.7 +/- 4.4, respectively] in all subjects. The difference
      in potentiation of VE-VCO2 by CO2 and DS loading was not due to differences in
      mean chemical drive or changes in breathing pattern. Thus changes in the profile
      of airway CO2 influx may have an independent influence on ventilatory CO2
      exercise interaction. Peripheral chemoreceptors mediation, although important, is
      not obligatory for this behavior.

PMID- 1399986
TI  - Parenchymal stability.
AB  - Both continuum and micromechanical models have been used to describe the
      mechanics of lung parenchyma. Different authors, using different models, have
      come to different conclusions about parenchymal stability. We show that the
      continuum model, augmented by bounds on the elastic moduli obtained from recent
      micromechanical modeling, yields the same conclusions about stability that have
      been obtained from purely micromechanical modeling: if the lung were homogeneous,
      it would be stable; local atelectasis would not occur at positive transpulmonary
      pressure. However, the same analysis yields the prediction that if the surface-to
      volume ratio is not uniform throughout the lung, regions of higher surface
      density collapse if surface tension is large and insensitive to surface area. A
      micromechanical model that illustrates regional collapse is described.

PMID- 1399987
TI  - Acute and chronic pulmonary vasoconstriction after left lung autotransplantation
      in conscious dogs.
AB  - We investigated the acute and chronic effects of left lung autotransplantation
      (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in
      conscious dogs. Continuous LP/Q plots were generated in chronically instrumented
      conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented
      normal conscious dogs were studied at equal time points post-surgery. LLA had
      little or no effect on baseline systemic hemodynamics or blood gases. In
      contrast, compared with normal conscious dogs, striking active flow-independent
      pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q
      relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/-
      0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar
      magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post
      LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the
      left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial
      blood gases were unchanged when total pulmonary blood flow was directed to
      exclusively perfuse the transplanted left lung. Thus, LLA results in both acute
      and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a
      useful stable experimental model to assess the specific effects of surgical
      transplantation on pulmonary vascular regulation.

PMID- 1399988
TI  - Effects of acute oligohydramnios on respiratory system of fetal sheep.
AB  - Prolonged oligohydramnios, or a lack of amniotic fluid, is associated with
      pulmonary hypoplasia and subsequent perinatal morbidity, but it is unclear
      whether short-term or acute oligohydramnios has any effect on the fetal
      respiratory system. To investigate the acute effects of removal of amniotic
      fluid, we studied nine chronically catheterized fetal sheep at 122-127 days
      gestation. During a control period, we measured the volume of fluid in the fetal
      potential airways and air spaces (VL), production rate of that fluid, incidence
      and amplitude of fetal breathing movements, tracheal pressures, and fetal plasma
      concentrations of cortisol, epinephrine, and norepinephrine. We then drained the
      amniotic fluid for a short period of time [24-48 h, 30.0 +/- 4.0 (SE) h] and
      repeated the above measurements. The volume of fluid drained for the initial
      studies was 1,004 +/- 236 ml. Acute oligohydramnios decreased VL from 35.4 +/-
      2.9 ml/kg during control to 22.0 +/- 1.6 after oligohydramnios (P less than
      0.004). Acute oligohydramnios did not affect the fetal lung fluid production
      rate, fetal breathing movements, or any of the other measured variables. Seven
      repeat studies were performed in six of the fetuses after reaccumulation of the
      amniotic fluid at 130-138 days, and in four of these studies the lung volume also
      decreased, although the overall mean for the repeat studies was not significantly
      different (27.0 +/- 5.2 ml/kg for control vs. 25.5 +/- 5.5 ml/kg for
      oligohydramnios). Again, none of the other measured variables were altered by
      oligohydramnios in the repeat studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399989
TI  - Effects of thromboxane synthase inhibition on tumor necrosis factor-induced lung
      injury in sheep.
AB  - To examine the role of thromboxane (Tx) A2 in the pathogenesis of acute lung
      injury caused by tumor necrosis factor alpha (TNF), we tested the effects of OKY
      046, a selective thromboxane synthase inhibitor, on pulmonary hemodynamics, lung
      lymph balance, circulating leukocytes, arterial blood gas analysis, and TxA2 (as
      TxB2) and prostacyclin (as 6-keto-prostaglandin F1 alpha) levels in plasma and
      lung lymph after TNF infusion in awake sheep. Infusion of human recombinant TNF
      (3.5 micrograms/kg) into a chronically instrumented awake sheep caused a
      transient increase in pulmonary arterial pressure (Ppa). The Ppa peaked within 15
      min of the start of TNF infusion from 23.3 +/- 1.1 (SE) cmH2O of baseline to 42.3
      +/- 2.3 cmH2O and then decreased toward baseline. The pulmonary hypertension was
      accompanied by transient hypoxemia, peripheral leukopenia, and the increases in
      TxB2 in plasma and lung lymph. These changes were followed by an increase in flow
      of protein-rich lung lymph, consistent with an increase in pulmonary
      microvascular permeability. OKY-046 significantly prevented the rises of Ppa and
      TxB2 concentrations in plasma and lung lymph during early phase after TNF
      infusion. OKY-046, however, did not attenuate the increase of lung lymph flow,
      transient hypoxemia, and leukopenia. From these data, and by comparison with our
      previous studies of OKY-046-pretreated sheep during endotoxemia, we conclude that
      TxA2 has an important role of the increase in the early pulmonary hypertension,
      but it is not related to the early hypoxemia, leukopenia, and lung lymph balances
      in TNF-induced lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399990
TI  - NANC nerve pathways controlling mucus glycoconjugate secretion into feline
      trachea.
AB  - We used autonomic-blocking drugs to define nonadrenergic noncholinergic (NANC)
      vagus nerve pathways regulating tracheal mucus secretion. In anesthetized cats,
      mucus glycoconjugates, radiolabeled biosynthetically with [35S]sulfate and
      [3H]glucose, were washed from a tracheal segment in situ and dialyzed before
      scintillation counting and chemical assay with periodic acid-Schiff (PAS).
      Without autonomic blockade, vagal stimulation (9.5 Hz, 10 V, 2-ms pulse width, 10
      min duration) increased outputs of radiolabeled and PAS-reactive glycoconjugates
      repeatably over four stimulation periods. In other animals, vagus nerves were
      stimulated with administration of autonomic blockers between stimulations. The
      first stimulation (no blockers) increased glycoconjugate output (delta 35S = 221
      +/- 43.3%, delta 3H = 58 +/- 13.8%; delta PAS = +299 +/- 82.7%). Atropine,
      phentolamine, and propranolol reduced these responses (delta 35S = 67 +/- 15.6%;
      delta 3H = 26 +/- 5.3%; delta PAS = 88 +/- 25.6%). Guanethidine did not
      significantly lessen them further, although delta 3H was no longer significant.
      Ganglion blockade with hexamethonium prevented most of the remaining response to
      vagal stimulation (P less than 0.05 for diminution of delta 35S and delta PAS),
      but small effects persisted (delta 35S = 17 +/- 5.6%; delta PAS = 20 +/- 6.8%; P
      less than 0.05). We conclude that the main NANC vagal pathway controlling
      tracheal glycoconjugate secretion runs orthodromically.

PMID- 1399991
TI  - Variation and limitations in fiber enzymatic and size responses in hypertrophied
      muscle.
AB  - The present study was designed to determine whether the degree and kind of
      adaptation of a muscle fiber to a functional overload (FO) are determined by
      properties that are intrinsic to that fiber. The study also addresses the
      question of the capability of fibers to maintain a normal level of coordination
      of proteins per fiber as fiber volume changes dramatically. The plantaris muscle
      of six adult female cats was overloaded for 12 wk by bilateral synergist removal.
      Plantaris muscle fiber mean size doubled after FO, although some very small
      fibers that stained dark for adenosinetriphosphatase (ATPase) were observed in
      some of the FO muscles. There appeared to be no change in total succinate
      dehydrogenase activity per fiber. A reduction in succinate dehydrogenase activity
      per unit volume was observed in a substantial number of fibers, reflecting a
      disproportionate increase in fiber volume relative to mitochondrial volume. In
      contrast, total alpha-glycerophosphate dehydrogenase activity and actomyosin
      ATPase activity increased as fiber size increased, whereas there was no change in
      alpha-glycerophosphate dehydrogenase and ATPase activities per unit volume.
      Control and FO muscle fibers generally expressed either a fast or slow myosin
      heavy chain type, but in some cases FO muscle fibers expressed both fast and slow
      myosin heavy chains. The persistence of variability in fiber sizes and enzyme
      activities in fibers of overloaded muscles suggests a wide range in the adaptive
      potential of individual fibers to FO. These data indicate that a severalfold
      increase in cell size may occur without significant qualitative changes in the
      coordination of protein regulation associated with metabolic pathways and ATP
      utilization.

PMID- 1399992
TI  - Upper airway anesthesia delays arousal from airway occlusion induced during human
      NREM sleep.
AB  - Six healthy subjects (5 males and 1 female, 26-40 yr old) were studied during non
      rapid-eye-movement (NREM) sleep to assess the role of upper airway (UA) afferents
      in the arousal response to induced airway occlusion. Subjects wore an airtight
      face mask attached to a low-resistance one-way valve. A valve in the inspiratory
      circuit allowed instantaneous inspiratory airway occlusion and release; the
      expiratory circuit remained unoccluded at all times. Each subject was studied
      during two nights. On one night, occlusions were created during stable stage 2
      NREM sleep before and after application of 4% lidocaine to the oral and nasal
      mucosa. On the other night, the protocol was duplicated with saline ("sham
      anesthesia") rather than lidocaine. The order of nights was randomized.
      Occlusions were sustained until electroencephalographic arousal. Three to 12
      occlusions were performed in each subject for each of the four parts of the
      protocol (pre- and post-lidocaine, pre- and post-saline). The auditory threshold
      for arousal (1,500-Hz tone beginning at 30 dB) was also tested before and after
      UA lidocaine. For the group, arousal time after UA anesthesia was prolonged
      compared with preanesthesia arousal time (P less than 0.001); arousal time after
      sham anesthesia did not significantly increase from before sham anesthesia (P =
      0.9). The increase in arousal time with UA anesthesia was greater than the
      increase with sham anesthesia (P less than 0.001). The auditory arousal threshold
      did not increase after UA anesthesia. Inspiratory mask pressure, arterial O2
      saturation of hemoglobin, and end-tidal PCO2 during occlusions were similar
      before and after UA anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1399993
TI  - Contrasting effects of prostaglandins E2 and F2 alpha on sensitivity of the human
      cough reflex.
AB  - Prostaglandins have been shown to influence the sensitivity of the cough reflex.
      To investigate putative mechanisms of this, we examined the effects of inhaled
      prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) on human cough responses
      elicited by two challenges, low chloride solution and capsaicin, which may
      activate different neural pathways. Baseline cough challenges were followed after
      2 h by five breaths of PGE2, PGF2 alpha, or citric acid as a control. Cough
      challenges were repeated after 1 min. Potentiation of capsaicin responses
      occurred after PGE2 (median increase 2 coughs/min, range 0-7, P less than 0.01)
      and PGF2 alpha (median increase 8 coughs/min, range -3 to 27, P less than 0.01)
      compared with control. The effect of PGF2 alpha was greater (P less than 0.05)
      than that of PGE2. Potentiation of low chloride responses also occurred after
      PGF2 alpha (median increase 7 coughs/2 min, range -1 to 19, P less than 0.01),
      but effects of PGE2 were insignificant against this challenge (median change -1
      coughs/2 min, range -4 to 13). These data suggest that PGE2 and PGF2 alpha have
      different effects on the sensitivity of the human cough reflex, which may be
      relevant during airway disease.

PMID- 1399994
TI  - Increased venous pressure causes increased thoracic duct pressure in awake sheep.
AB  - The lymph from most organs drains through the thoracic duct and into veins in the
      neck. We hypothesized that increases in neck vein pressure (Pnv) are reflected
      through the thoracic duct to the lung lymphatic-thoracic duct junction. To test
      this, we cannulated the lung lymphatics in the direction of flow in four sheep.
      We advanced each cannula until it entered the thoracic duct. Thus the pressure at
      the tip of the lymphatic cannula (Px) was the pressure at the outflow of the lung
      lymphatics. We also placed a balloon into the superior vena cava. One to two days
      later, we measured Px in the awake sheep as we inflated the balloon and increased
      Pnv in steps to 25-45 cmH2O. We found no significant differences in Px and Pnv.
      Furthermore, Px closely followed Pnv after each step increase in Pnv. These
      results support our hypothesis that increases in Pnv cause increases in the
      outflow pressure to lung lymphatics.

PMID- 1399995
TI  - Short-duration spaceflight impairs human carotid baroreceptor-cardiac reflex
      responses.
AB  - Orthostatic intolerance is a predictable but poorly understood consequence of
      space travel. Because arterial baroreceptors modulate abrupt pressure transients,
      we tested the hypothesis that spaceflight impairs baroreflex mechanisms. We
      studied vagally mediated carotid baroreceptor-cardiac reflex responses (provoked
      by neck pressure changes) in the supine position and heart rate and blood
      pressure in the supine and standing positions in 16 astronauts before and after 4
      to 5-day Space Shuttle missions. On landing day, resting R-R intervals and
      standard deviations, and the slope, range, and position of operational points on
      the carotid transmural pressure-sinus node response relation were all reduced
      relative to preflight. Stand tests on landing day revealed two separate groups
      (one maintained standing arterial pressure better) that were separated by
      preflight slopes, operational points, and supine and standing R-R intervals and
      by preflight-to-postflight changes in standing pressures, body weights, and
      operational points. Our results suggest that short-duration spaceflight leads to
      significant reductions in vagal control of the sinus node that may contribute to,
      but do not account completely for, orthostatic intolerance.

PMID- 1399996
TI  - Failure of pulmonary acidosis to increase respiratory drive.
AB  - Experiments were performed to determine whether increases in acidity isolated to
      the pulmonary circulation would stimulate hypothesized pulmonary chemoreceptors
      and increase respiratory drive in the anesthetized paralyzed mechanically
      ventilated cat (n = 9). Respiratory drive was assessed by measuring the frequency
      and amplitude of the integrated phrenic neurogram. To create an isolated
      pulmonary acidosis, blood returning to the lung was acidified by infusion of 0.3
      M lactic acid (1.91 ml/min) into the inferior vena cava, while systemic arterial
      pH was restored to near normal levels by simultaneous infusion of base (0.3 M
      NaOH) into the left atrium. Six minutes after the start of this dual infusion of
      acid and base, right ventricular (pulmonary) pH decreased from 7.286 to 7.179 and
      PCO2 increased 7 Torr. Systemic arterial pH and PCO2 were unchanged from
      measurements immediately before the infusion. This level of pulmonary acidosis
      failed to increase respiratory drive as assessed by phrenic activity. To test the
      sensitivity of the preparation to known systemic arterial chemical stimuli, a
      combined pulmonary and systemic acidosis was elicited by infusion of 0.3 M lactic
      acid into the inferior vena cava and 0.3 M NaCl into the left atrium. This
      infusion significantly lowered both systemic arterial and pulmonary arterial pH
      (7.343 to 7.155 for systemic arterial pH and 7.286 to 7.067 for pulmonary pH) and
      increased phrenic efferent activity 45%. We conclude that phrenic efferent
      activity is unaffected by moderate reductions in the pH of the pulmonary
      circulation in the absence of a significant systemic arterial acidosis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1399997
TI  - PEEP is necessary for exogenous surfactant to reduce pulmonary edema in canine
      aspiration pneumonitis.
AB  - Alveolar edema inactivates surfactant, and surfactant depletion causes edema by
      reducing lung interstitial pressure (Pis). We reasoned that surfactant repletion
      might reduce edema by raising Pis after acute lung injury and that positive end
      expiratory pressure (PEEP) might facilitate this effect. One hour after tracheal
      administration of hydrochloric acid in 18 anesthetized dogs with transmural
      pulmonary capillary wedge pressure of 8 Torr, the animals were randomized into
      three groups: in the SURF + PEEP group, 50 mg/kg of calf lung surfactant extract
      (CLSE) was instilled into each main stem bronchus with 8 cmH2O of PEEP; in the
      SAL + PEEP group, PEEP was followed by an equal volume of saline (SAL); in the
      SURF group, CLSE was given without PEEP. After 5 h, edema in excised lungs (wet
      to-dry weight ratios) was significantly less in the SURF + PEEP group (9.1 +/-
      1.0) than in the other groups (11.3 +/- 1.8 and 11.3 +/- 1.8, respectively). In
      the SURF + PEEP group, pulmonary venous admixture fell by 6%; this change was
      different from the 7% increase in the SAL + PEEP group and 40% increase in the
      SURF group (P less than 0.05). Airway secretions obtained in the SURF + PEEP
      group had normal minimum surface tensions of 4 +/- 2 mN/m, a value much lower
      than in SAL + PEEP and SURF groups (32 +/- 4 and 22 +/- 7 mN/m, respectively). We
      conclude that surfactant normalizes surface tension and decreases transcapillary
      hydrostatic forces in this lung injury model, thereby reducing edema formation
      and improving gas exchange. These benefits occur only if surfactant is given with
      PEEP, allowing surfactant access to the alveoli and/or minimizing its inhibition
      by edema proteins.

PMID- 1399998
TI  - Oxygen radical scavengers protect against eosinophil-induced injury in isolated
      perfused rat lungs.
AB  - The protective effect of oxygen radical scavengers on lung injury induced by
      activated eosinophils was examined in isolated perfused rat lungs. Eosinophils
      were obtained by bronchoalveolar lavage from rats infected with Toxocara canis
      and activated with phorbol myristate acetate (PMA). There were no changes in
      pulmonary vascular (RT) and airway (Raw) resistances and only minimal changes in
      vascular permeability assessed using the capillary filtration coefficient (Kf,c)
      in PMA control lungs and nonactivated eosinophil-treated lungs. In lungs
      receiving 3 x 10(6) PMA-activated eosinophils, there were significant increases
      from baseline of 7.3-fold in RT at 30 min, primarily due to the constriction of
      small arteries and veins; 3.6-fold in Kf,c at 90 and 130 min; and 2.5-fold in
      Raw. The lungs also became markedly edematous. Both superoxide dismutase and
      catalase pretreatment prevented the significant increase in Kf,c and lung wet-to
      dry weight ratios and partially attenuated the increase in Raw, but did not
      significantly inhibit the increase in RT induced by activated eosinophils. Heat
      inactivated catalase did not attenuate the eosinophil-induced increases in Kf,c,
      Raw, or RT. Thus, activated eosinophils acutely increased microvascular
      permeability primarily through production of oxygen free radicals. The free
      radical scavengers superoxide dismutase and catalase partially attenuated the
      bronchoconstriction but had no significant effect on the vasoconstriction induced
      by activated eosinophils.

PMID- 1399999
TI  - Role of neutrophil elastase in allergen-induced lysozyme secretion in the dog
      trachea.
AB  - To test our hypothesis that neutrophil elastase plays a role in airway
      hypersecretion associated with the allergic late-phase response, using an
      isolated tracheal segment system in vivo and measuring lysozyme activity in the
      perfusate of the lumen as a marker of submucosal gland secretion over 8 h, we
      studied the response of five allergic dogs to ragweed. The dogs were exposed on
      separate occasions to specific allergen, to allergen vehicle, and to allergen in
      the presence of a selective neutrophil elastase inhibitor, ICI 200,355. Allergen
      exposure caused a marked increase in lysozyme secretion that was significantly
      increased at 4, 6, and 8 h compared with controls and ICI 200,355-treated dogs.
      Neutrophil elastase appeared in the perfusate after allergen exposure and was
      positively correlated with lysozyme secretion at 8 h. These findings suggest that
      neutrophil elastase plays an important role as a secretagogue in the allergic
      late-phase response.

PMID- 1400000
TI  - Reductions of neural activities to upper airway muscles after elevations in
      static lung volume.
AB  - We evaluated the hypothesis that the tonic discharge of pulmonary stretch
      receptors significantly influences the respiratory-modulated activities of
      cranial nerves. Decerebrate and paralyzed cats were ventilated with a servo
      respirator, which produced changes in lung volume in parallel with integrated
      phrenic activity. Activities of the facial, hypoglossal, and recurrent laryngeal
      nerves and nerves to the thyroarytenoid muscle and triangularis sterni were
      recorded. After a stereotyped pattern of lung inflation, tracheal pressure was
      held at 1, 2, 4, or 6 cmH2O during the subsequent ventilatory cycle. Increases in
      tracheal pressure caused progressive reductions in both inspiratory and
      expiratory cranial nerve activities and progressive elevations in triangularis
      sterni discharge; peak levels of phrenic activity declined modestly. Similar
      changes were observed in normocapnia and hypercapnia. We conclude that the tonic
      discharge of pulmonary stretch receptors is an important determinant of the
      presence and magnitude of respiratory-modulated cranial nerve activity. This
      reflex mechanism may maintain upper airway patency and also regulate expiratory
      airflow.

PMID- 1400001
TI  - Acute and long-term TNF-alpha administration increases pulmonary vascular
      reactivity in isolated rat lungs.
AB  - Tumor necrosis factor-alpha (TNF-alpha) causes pulmonary hypertension and
      arterial hypoxemia, but the mechanisms are unknown. We conducted two experiments
      to test the hypothesis that TNF-alpha alters pulmonary vascular reactivity, which
      in turn could cause either pulmonary hypertension or arterial hypoxemia. In
      experiment 1, rats were given acute or long-term injections of TNF-alpha
      (recombinant human) in vivo. Rats treated acutely received either saline or TNF
      alpha (40 micrograms/kg iv in saline) 3 min (TNF-3 min; n = 8), 20 min (TNF-20
      min; n = 8), or 24 h (TNF-24 h; n = 5) before the lungs were isolated. Rats
      treated chronically received injections of either saline or TNF-alpha (250
      micrograms/kg ip in saline) two times per day for 7 days (TNF-7 days; n = 9).
      Lungs were isolated and perfused with Earle's salt solution (+2 g/l NaHCO3 + 4
      g/100 ml Ficoll), and vascular reactivity was tested with acute hypoxia (3 min;
      3% O2) and angiotensin II (ANG II; 0.025-0.40 micrograms). Pulmonary pressor
      responses to hypoxia were greater (P less than 0.05) in TNF-20 min and TNF-7 day
      groups. ANG II responses were increased (P less than 0.05) in TNF-7 day rats. In
      experiment 2, lungs were isolated and perfused and received direct pulmonary
      arterial injections of TNF-alpha (0.2, 2.0, and 20 micrograms) or saline, after
      stable responses to hypoxia and ANG II (0.10 microgram) were attained. Reactivity
      was not different between control and TNF-alpha rats before the injections, but
      TNF-alpha increased (P less than 0.05) responses to hypoxia and ANG II.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1400002
TI  - Effect of regular voluntary exercise on resting cardiovascular responses in SHR
      and WKY pregnant rats.
AB  - The purpose of this study was to assess the influence of regular voluntary
      exercise in pregnant normotensive Wistar-Kyoto (WKY) and spontaneously
      hypertensive (SHR) rats on 1) uteroplacental perfusion and mean arterial pressure
      in the resting conscious condition and 2) fetal number, fetal weight, and number
      of fetal resorptions. WKYs and SHRs were randomly assigned to standard cages
      [CWKY (n = 10); CSHR (n = 6)] or cages with activity wheels [EWKY (n = 7); ESHR
      (n = 8)]. EWKYs and ESHRs exercised for 12 wk, and then all rats were bred and
      experiments were conducted on gestational day 17. Resting blood flow
      (microspheres), heart rate (HR), and mean arterial pressure (Pa) were measured.
      No significant difference was found in Pa, HR, uterine blood flow (ESHRs 52 +/- 8
      ml.min-1.100 g-1; CSHRs 28 +/- 6 ml.min-1.100 g-1), or maternal placental blood
      flow (ESHRs, 122 +/- 31 ml.min-1.100 g-1; CSHRs 78 +/- 21 ml.min-1.100 g-1) among
      the groups. Exercise altered the relationship between maternal placental and
      uterine blood flow and Pa in the SHR; SHRs with lower Pa maintained higher
      placental and uterine blood flow after training. Before gestation ESHRs ran on
      average more kilometers per week than EWKYs (43 +/- 3 vs. 34 +/- 4), but during
      gestation ESHRs averaged fewer kilometers per week than EWKYs (16 +/- 4 vs. 22 +/
      4). Succinate dehydrogenase activity was higher in the white vastus lateralis
      (1.02 +/- 0.2 mumol cytochrome c reduced.min-1.g wet wt-1) and vastus intermedius
      (3.1 +/- 0.5 mumol cytochrome c reduced.min-1.g wet wt-1) muscles of
      ESHRs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400003
TI  - Role of O2 in regulating tissue respiration in dog muscle working in situ.
AB  - This study was designed to investigate the role of tissue oxygenation in some of
      the factors that are thought to regulate muscle respiration and metabolism.
      Tissue oxygenation was altered by reductions in O2 delivery (muscle blood flow x
      arterial O2 content), induced by decreases in arterial PO2 (PaO2). O2 uptake
      (VO2) was measured in isolated in situ canine gastrocnemius at rest and while
      working at two stimulation intensities (isometric tetanic contractions at 0.5 and
      1 contractions/s) on three separate occasions, with only the level of PaO2 (78,
      30, and 21 Torr) being different for each occasion. Muscle blood flow was held
      constant (pump perfusion) at each work intensity for the three different levels
      of PaO2. Muscle biopsies were obtained at the end of each rest and work period.
      Muscle VO2 was significantly less (P less than 0.05) at both stimulation
      intensities for the hypoxemic conditions, whereas [ATP] was reduced only during
      the highest work intensity during both hypoxemic conditions (31% reduction at 21
      Torr PaO2 and 17% at 30 Torr). For each level of PaO2, the relationships between
      the changes that occurred in VO2 and levels of phosphocreatine, ADP, and
      ATP/ADP.P(i) as the stimulation intensity was increased were significantly
      correlated; however, the slopes and intercepts of these lines were significantly
      different for each PaO2. Thus a greater change in any of the proposed regulators
      of tissue respiration (e.g., phosphocreatine, ADP) was required to achieve a
      given VO2 as PaO2 was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400004
TI  - Modeling the effects of hypoxia on ATP turnover in exercising muscle.
AB  - Most models of metabolic control concentrate on the regulation of ATP production
      and largely ignore the regulation of ATP demand. We describe a model, based on
      the results of Hogan et al. (J. Appl. Physiol. 73: 728-736, 1992), that
      incorporates the effects of ATP demand. The model is developed from the premise
      that a unique set of intracellular conditions can be measured at each level of
      ATP turnover and that this relationship is best described by energetic state.
      Current concepts suggest that cells are capable of maintaining oxygen consumption
      in the face of declines in the concentration of oxygen through compensatory
      changes in cellular metabolites. We show that these compensatory changes can
      cause significant declines in ATP demand and result in a decline in oxygen
      consumption and ATP turnover. Furthermore we find that hypoxia does not directly
      affect the rate of anaerobic ATP synthesis and associated lactate production.
      Rather, lactate production appears to be related to energetic state, whatever the
      PO2. The model is used to describe the interaction between ATP demand and ATP
      supply in determining final ATP turnover.

PMID- 1400005
TI  - Autoresuscitation: a survival mechanism in piglets.
AB  - Piglets were studied to determine 1) the cardiovascular and neurophysiological
      effects of prolonged laryngeal-induced respiratory inhibition (n = 7) and 2)
      whether these effects were modulated by autonomic blockade (n = 6). Respiration,
      electrocardiogram, electroencephalogram (EEG), and blood pressure were recorded,
      and blood gases were measured. During continuous laryngeal stimulation in the
      presence of light anesthesia, apnea was interrupted every 1-2.5 min by clusters
      of two to six breaths. Compared with control, these breaths had a significantly
      greater tidal volume (430 +/- 30% of control), shorter inspiratory time (87 +/-
      5%), and longer expiratory time (124 +/- 15%) and, thus, were of a gasping
      nature. With each cluster of gasps, arterial PO2 increased from 15 +/- 2 to 56 +/
      5 Torr, heart rate from 84 +/- 7 to 161 +/- 5 beats/min, and mean blood pressure
      from 48 +/- 4 to 106 +/- 6 mmHg. The EEG became flat by 1 min after the onset of
      apnea and remained isoelectric throughout the stimulus period. Cyclical gasps
      were not affected by sympathetic or parasympathetic blockade. These data show
      that, despite EEG silence, piglets can autoresuscitate by initiating gasps that
      are not dependent on autonomic integrity. These gasps markedly improve
      cardiovascular status and may sustain animals for a prolonged period of time.

PMID- 1400006
TI  - 24-hour homeodynamic states of arterial blood pressure and pulse interval in
      conscious rats.
AB  - In models that describe the homeostasis of the circulation, arterial blood
      pressure is usually expressed as a single value, which is regarded as the set
      point in such systems. The aim of the study was to identify in rats from 24-h
      beat-to-beat recordings the value of blood pressure that describes best such a
      set point of the cardiovascular system. Normotensive Wistar-Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR), kept on a 12:12-h lights on-off cycle,
      were instrumented for computerized 24-h beat-to-beat recording of mean arterial
      pressure (MAP) and pulse interval (PI). Three-dimensional frequency distributions
      were constructed by plotting for each beat its MAP vs. its PI. During the dark
      period, the concurrent distribution of MAP and PI showed two distinct modes while
      during the light period a single mode was found. Comparable patterns were found
      in SHRs and WKYs. These three different modes were significantly different from
      the mathematically calculated mean values of MAP and PI over these periods. Thus
      in rats the 24-h behavior of the cardiovascular system is better described by
      dynamic shifts between different modes (homeodynamic states) than by a single set
      point.

PMID- 1400007
TI  - Pharyngeal dilation associated with cricothyroid muscle contraction in dogs.
AB  - The mechanical function of phasic respiratory-related activity of the
      cricothyroid muscle of the larynx is poorly understood. We studied five adult
      cross-bred dogs (weight 14-20 kg) deeply anesthetized with pentobarbitone sodium,
      mechanically ventilated via a tracheostomy, and placed prone with the mouth open.
      Bilateral cricothyroid muscle contraction was induced by supramaximal electrical
      stimulation of the external branches of the superior laryngeal nerve.
      Computerized axial tomography was used to assess effects of cricothyroid muscle
      contraction. During cricothyroid muscle contraction, oropharyngeal (tip of
      epiglottis) cross-sectional area increased by 18.0 +/- 3.0% (SE) (P = 0.008),
      whereas combined left and right piriform recess cross-sectional area increased by
      85 +/- 25% (n = 4; P = 0.02) at the midepiglottic level and by 152 +/- 37% (P =
      0.01) at the base of the epiglottis. Furthermore, at the base of the epiglottis
      the maximum horizontal distance between the alae of the thyroid cartilage
      increased by 21 +/- 8% (P = 0.05). In contrast, lateral glottic diameter
      decreased by 52 +/- 2% (n = 4; P = 0.01), whereas dorsoventral glottic diameter
      increased by 18 +/- 5% (n = 4; P less than 0.02). The cricothyroid muscle,
      therefore, has the capacity to act simultaneously as a pharyngeal dilator and a
      glottic constrictor and thus may play a role in the control of oropharyngeal as
      well as laryngeal patency.

PMID- 1400008
TI  - Protein requirements and muscle mass/strength changes during intensive training
      in novice bodybuilders.
AB  - This randomized double-blind cross-over study assessed protein (PRO) requirements
      during the early stages of intensive bodybuilding training and determined whether
      supplemental PRO intake (PROIN) enhanced muscle mass/strength gains. Twelve men
      [22.4 +/- 2.4 (SD) yr] received an isoenergetic PRO (total PROIN 2.62 g.kg-1.day
      1) or carbohydrate (CHO; total PROIN 1.35 g.kg-1.day-1) supplement for 1 mo each
      during intensive (1.5 h/day, 6 days/wk) weight training. On the basis of 3-day
      nitrogen balance (NBAL) measurements after 3.5 wk on each treatment (8.9 +/- 4.2
      and -3.4 +/- 1.9 g N/day, respectively), the PROIN necessary for zero NBAL
      (requirement) was 1.4-1.5 g.kg-1.day-1. The recommended intake (requirement + 2
      SD) was 1.6-1.7 g.kg-1.day-1. However, strength (voluntary and electrically
      evoked) and muscle mass [density, creatinine excretion, muscle area (computer
      axial tomography scan), and biceps N content] gains were not different between
      diet treatments. These data indicate that, during the early stages of intensive
      bodybuilding training, PRO needs are approximately 100% greater than current
      recommendations but that PROIN increases from 1.35 to 2.62 g.kg-1.day-1 do not
      enhance muscle mass/strength gains, at least during the 1st mo of training.
      Whether differential gains would occur with longer training remains to be
      determined.

PMID- 1400009
TI  - Expression of muscle capillary alkaline phosphatase is affected by hypoxia.
AB  - Hypoxia stimulates angiogenesis in some microvascular beds, but no clear
      angiogenic effect of hypoxia has yet been demonstrated in adult skeletal muscle.
      In this study the distribution of alkaline phosphatase (APase) was compared with
      a novel microvascular marker, Griffonia simplicifolia I (GSI), to determine
      whether the respective markers were expressed by muscle capillaries during
      hypoxic conditions and to probe for the presence or absence of angiogenesis in
      response to short-term hypoxia. Mice were exposed to normobaric 8% oxygen for 7
      or 21 days. Capillary density in the red and white areas of the gastrocnemius
      muscle was determined with the use of a double-labeling procedure for both APase
      and fluorescently tagged GSI. Little change in capillary density was found. Focal
      reductions in APase activity were observed within 1 wk of hypoxia, but no changes
      were observed in GSI binding. In controls, 74 and 92% of red and white muscle
      capillaries, respectively, were APase positive. This percentage declined to 60%
      in red and 43% in white muscle after 21 days of hypoxia. The results indicate
      that APase expression is labile under certain conditions and warrant a cautious
      approach to using the enzyme as a marker. Binding of the GSI lectin to muscle
      capillaries appeared to be unchanged by the exposure to hypoxia, indicating
      stability of this marker system. No significant change in the number of
      capillaries around individual muscle fibers was evident at 21 days when GSI was
      used to detect capillaries. These results confirm the absence of hypoxia-induced
      angiogenesis in muscle capillaries during the time period studied.

PMID- 1400010
TI  - Modification of bronchial reactivity by physiological concentrations of plasma
      epinephrine.
AB  - Circulating epinephrine concentrations are altered in certain pathophysiological
      states, but whether such changes in epinephrine concentrations can alter
      bronchial responsiveness in subjects with asthma has not been studied. We studied
      10 subjects with asthma in a double-blind crossover study on 4 nonconsecutive
      days. After measurement of baseline forced expiratory volume in 1 s (FEV1) and
      plasma epinephrine concentration, subjects were given placebo or 4, 16, or 64
      ng.kg-1.min-1 epinephrine by intravenous infusion for 45 min. Blood was taken for
      plasma epinephrine concentration before the infusion and at 30 min, when a
      histamine challenge test was performed. Mean plasma epinephrine concentrations
      ranged from 0.37 nmol/l on placebo to 3.76 nmol/l with the 64-ng/kg infusion.
      FEV1 increased progressively with increasing concentrations of infused
      epinephrine, the mean change ranging from -0.051 on placebo to 0.331 after the
      highest concentration of epinephrine. The provocative dose of histamine causing a
      20% fall in FEV1 increased progressively with increasing concentrations of
      infused epinephrine, geometric mean values ranging from 0.61 mumol with placebo
      to 1.7 mumol after the highest dose of epinephrine. Thus epinephrine, at
      physiological plasma concentrations, can modify bronchial reactivity.

PMID- 1400011
TI  - Endotoxin tolerance is associated with altered GTP-binding protein function.
AB  - Previous studies have suggested that guanine nucleotide regulatory (G) proteins
      modulate endotoxin-stimulated peritoneal macrophage arachidonic acid (AA)
      metabolism. Endotoxin-stimulated metabolism of AA by peritoneal macrophages is
      decreased in endotoxin tolerance (Rogers et al. Prostaglandins 31: 639-650,
      1986). These observations led to a study of G protein function and AA metabolism
      by peritoneal macrophages in endotoxin tolerance. Endotoxin tolerance was induced
      by the administration of sublethal doses of endotoxin. AA metabolism was assessed
      by measurement of thromboxane B2 (TxB2), a cyclooxygenase metabolite. NaF (5 mM),
      an activator of G proteins, significantly stimulated TxB2 synthesis in control
      macrophages from 7.7 +/- 0.2 to 19.1 +/- 0.6 (SE) ng/ml (P less than 0.05) at 2 h
      and was partially inhibited by pertussis toxin, suggesting a G protein-dependent
      mechanism. Salmonella enteritidis endotoxin (50 micrograms/ml) stimulated a
      similar increase in TxB2 levels (23 +/- 0.4 ng/ml, P less than 0.05). In contrast
      to control macrophages, macrophages from endotoxin-tolerant rats stimulated with
      either NaF or S. enteritidis endotoxin had TxB2 levels that were only 30 and 2%
      of the respective stimulated control cells. Basal guanosine-triphosphatase
      (GTPase) activity (33 +/- 6 pmol.mg-1.min-1) in endotoxin-tolerant macrophage
      membranes was significantly lower (P less than 0.05) than control basal activity
      (158 +/- 5 pmol.mg-1.min-1). This suppression of macrophage GTPase activity was
      apparent 48 h after the first in vivo sublethal endotoxin injection (100
      micrograms/kg ip). The reduced GTPase activity paralleled in vitro cellular
      hyporesponsiveness to endotoxin-stimulated TxB2 production.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1400012
TI  - Coordination of wingbeat and respiration in the Canada goose. I. Passive wing
      flapping.
AB  - The effects of passive wing flapping on respiratory pattern were examined in
      decerebrate Canada geese. The birds were suspended dorsally with two spine clamps
      while the extended wings were continuously moved up and down with a device
      designed to reproduce actual wing flapping. Passive wing motion entrained
      respiration over limited ranges by both increasing and decreasing the respiratory
      period relative to rest. All ratios of wingbeat frequency to respiratory
      frequency seen during free flight (Soc. Neurosci. Abstr. 15: 391, 1989) were
      produced during passive wing flapping. In addition, the phase relationship
      between wingbeat frequency and respiratory frequency, inspiration starting near
      the peak of wing upstroke, was similar to that seen during free flight and was
      unaffected by perturbations of the wing-flapping cycle. Removal of all afferent
      activity from the wings did not affect the ability of continuous passive wing
      movement to entrain respiration. However, feedback from the wings was required to
      produce rapid within-breath shifts in the respiratory period in response to
      single wing flaps. In conclusion, although feedback from the chest wall/lung may
      be more important in producing entrainment during the stable conditions of
      passive wing flapping, wing-related feedback may be critically involved in
      mediating the rapid adjustments in respiratory pattern required to maintain
      coordination between wing and respiratory movements during free flight.

PMID- 1400013
TI  - Coordination of wingbeat and respiration in birds. II. "Fictive" flight.
AB  - To determine whether an interaction between central respiratory and locomotor
      networks may be involved in the observed coordination of wingbeat and respiratory
      rhythms during free flight in birds, we examined the relationship between
      wingbeat and respiratory activity in decerebrate Canada geese and Pekin ducks
      before and after paralysis. Locomotor activity was induced through electrical
      stimulation of brain stem locomotor regions. Respiratory frequency (fv) was
      monitored via pneumotachography and intercostal electromyogram recordings before
      paralysis and via intercostal and cranial nerve IX electroneurogram recordings
      after paralysis. Wingbeat frequency (fW) was monitored using pectoralis major
      electromyogram recordings before, and electroneurogram recordings after,
      paralysis. Respiratory and cardiovascular responses of decerebrate birds during
      active (nonparalyzed) and "fictive" (paralyzed) wing activity were qualitatively
      similar to those of a variety of vertebrate species to exercise. As seen during
      free flight, wingbeat and respiratory rhythms were always coordinated during
      electrically induced wing activity. Before paralysis during active wing flapping,
      coupling ratios (fW/fv) of 1:1, 2:1, 3:1, and 4:1 (wingbeats per breath) were
      observed. After paralysis, fW and fv remained coupled; however, 1:1 coordination
      predominated. All animals tested (n = 9) showed 1:1 coordination. Two animals
      also showed brief periods of 2:1 coupling. It is clear that locomotor and
      respiratory networks interact on a central level to produce a synchronized
      output. The observation that the coordination between fW and fv differs in
      paralyzed and nonparalyzed birds suggests that peripheral feedback is involved in
      the modulation of a centrally derived coordination.

PMID- 1400014
TI  - Graphite-like lubrication of mesothelium by oligolamellar pleural surfactant.
AB  - Six studies have been completed to reevaluate pleural surfactant as a possible
      boundary lubricant in mesothelial sliding. It is capable of remarkable antiwear
      action, giving a mean scar diameter on a standard "four-ball test" comparable to
      the best commercially available lubricants and reducing friction to values
      anticipated from lamellated solid lubricants such as graphite. Pleural surfaces
      displayed appreciable hydrophobicity, which was almost eliminated by rinsing with
      a lipid solvent from which phospholipid was recovered and quantified. These
      quantities indicated that equivalent of 7.3 adsorbed monolayers of surface-active
      phospholipid, which was in general agreement with the number of layers of a
      graphite-like surface coating visualized by electron microscopy by use of a novel
      fixation procedure that avoids conventional aldehydes known to destroy
      hydrophobic surfaces. Graphite-like (dry) lubrication by adsorbed surface-active
      phospholipid is discussed as an excellent lubrication system available wherever
      the distribution of fluid allows the pleura to make contact.

PMID- 1400015
TI  - Lung and chest wall impedances in the dog in normal range of breathing: effects
      of pulmonary edema.
AB  - We evaluated the effect of pulmonary edema on the frequency (f) and tidal volume
      (VT) dependences of respiratory system mechanical properties in the normal ranges
      of breathing. We measured resistance and elastance of the lungs (RL and EL) and
      chest wall of four anesthetized-paralyzed dogs during sinusoidal volume
      oscillations at the trachea (50-300 ml, 0.2-2 Hz), delivered at a constant mean
      airway pressure. Measurements were made before and after severe pulmonary edema
      was produced by injection of 0.06 ml/kg oleic acid into the right atrium. Chest
      wall properties were not changed by the injection. Before oleic acid, EL
      increased slightly with increasing f in each dog but was independent of VT. RL
      decreased slightly and was independent of VT from 0.2 to 0.4 Hz, but above 0.4 Hz
      it tended to increase with increasing flow, presumably due to the airway
      contribution. After oleic acid injection, EL and RL increased greatly. Large
      negative dependences of EL on VT and of RL on f were also evident, so that EL and
      RL after oleic acid changed two- and fivefold, respectively, within the ranges of
      f and VT studied. We conclude that severe pulmonary edema changes lung properties
      so as to make behavior VT dependent (i.e., nonlinear) and very frequency
      dependent in the normal range of breathing.

PMID- 1400016
TI  - Respiration and measurement of cardiac output by thermodilution and central or
      peripheral dye dilution.
AB  - Cardiac output as measured by indicator dilution methods during artificial
      ventilation shows differences up to +/- 35%. We studied the influence of
      spontaneous breathing on measurement of cardiac output by thermodilution (TD) and
      central (CDD) and peripheral dye dilution (PDD) in seven anesthetized dogs.
      Injection of indicator was timed at one of five chosen moments in a respiratory
      cycle. The indicator for TD was also used as solvent for indocyanine green.
      Results were normalized by the value obtained with injection at inspiratory
      onset. Results of the central dilution methods showed a slight but not
      significant difference between values measured with injection at 25 and 75% of
      the respiratory cycle: 105.7 and 98.0%, respectively, (TD) and 102.3 and 97.2%
      (CDD). Mean cardiac output determined by TD, CDD, or PDD was not significantly
      different. We conclude that 1) a reasonable estimate of cardiac output may be
      obtained by means of a single indicator-dilution curve and 2) the choice of the
      dilution method may be determined by practical considerations.

PMID- 1400017
TI  - Entrainment of respiratory rhythm to respiratory oscillations of arterial PCO2 in
      vagotomized dogs.
AB  - The aim of this study was to demonstrate that the medullary respiratory rhythm
      generator is capable of entraining to respiratory oscillations of arterial PCO2
      (CO2 oscillations). We used 10 anesthetized, paralyzed, vagotomized, and
      mechanically ventilated dogs. First, rate of mechanical ventilation was manually
      adjusted so that it matched the dog's spontaneous respiratory rate, which
      established a constant phase relationship between the mechanical ventilation and
      the burst of phrenic neurogram (initial phase). Then this phase relationship was
      temporally disturbed by a brief electrical stimulation of the superior laryngeal
      nerve (SLN). In the control group, the initial phase and the steady-state phase
      relationship after SLN stimulation were randomly distributed within the phase
      plane, implying no interaction between the respiratory center and mechanical
      ventilation. In contrast, when CO2 output from the lung was increased 2.6-fold
      above the control level by venous CO2 loading, the initial phase and the steady
      state phase after SLN stimulation were locked in such a way that the onset of the
      burst of phrenic neurogram coincided with the peak of CO2 oscillations. This was
      not demonstrated when the dog was made hyperoxic. We therefore conclude that the
      respiratory center could entrain to phasic chemical afferent inputs originating
      from CO2 oscillations, provided they are considerably amplified.

PMID- 1400018
TI  - Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles
      in normal men.
AB  - Studies of sleep influences on human pharyngeal and other respiratory muscles
      suggest that the activity of these muscles may be affected by non-rapid-eye
      movement (NREM) sleep in a nonuniform manner. This variable sleep response may
      relate to the pattern of activation of the muscle (inspiratory phasic vs. tonic)
      and peripheral events occurring in the airway. Furthermore, the ability of these
      muscles to respond to respiratory stimuli during NREM sleep may also differ. To
      systematically investigate the effect of NREM sleep on respiratory muscle
      activity, we studied two tonic muscles [tensor palatini (TP), masseter (M)] and
      two inspiratory phasic ones [genioglossus (GG), diaphragm (D)], also measuring
      the response of these muscles to inspiratory resistive loading (12 cmH2O.l-1.s)
      during wakefulness and NREM sleep. Seven normal male subjects were studied on a
      single night with intramuscular electrodes placed in the TP and GG and surface
      electrodes placed over the D and M. Sleep stage, inspiratory airflow, and moving
      time average electromyograph (EMG) of the above four muscles were continuously
      recorded. The EMG of both tonic muscles fell significantly (P less than 0.05)
      during NREM sleep [TP awake, 4.3 +/- 0.05 (SE) arbitrary units, stage 2, 1.1 +/-
      0.2; stage 3/4, 1.0 +/- 0.2. Masseter awake, 4.8 +/- 0.6; stage 2, 3.3 +/- 0.5;
      stage 3/4, 3.1 +/- 0.5]. On the other hand, the peak phasic EMG of both
      inspiratory phasic muscles (GG and D) was well maintained.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1400019
TI  - Effects of training on muscle O2 transport at VO2max.
AB  - To quantify the relative contributions of convective and peripheral diffusive
      components of O2 transport to the increase in leg O2 uptake (VO2leg) at maximum
      O2 uptake (VO2max) after 9 wk of endurance training, 12 sedentary subjects (age
      21.8 +/- 3.4 yr, VO2max 36.9 +/- 5.9 ml.min-1.kg-1) were studied. VO2max, leg
      blood flow (Qleg), and arterial and femoral venous PO2, and thus VO2leg, were
      measured while the subjects breathed room air, 15% O2, and 12% O2. The sequence
      of the three inspirates was balanced. After training, VO2max and VO2leg increased
      at each inspired O2 concentration [FIO2; mean over the 3 FIO2 values 25.2 +/-
      17.8 and 36.5 +/- 33% (SD), respectively]. Before training, VO2leg and mean
      capillary PO2 were linearly related through the origin during hypoxia but not
      during room air breathing, suggesting that, at 21% O2, VO2max was not limited by
      O2 supply. After training, VO2leg and mean capillary PO2 at each FIO2 fell along
      a straight line with zero intercept, just as in athletes (Roca et al. J. Appl.
      Physiol. 67: 291-299, 1989). Calculated muscle O2 diffusing capacity (DO2) rose
      34% while Qleg increased 19%. The relatively greater rise in DO2 increased the
      DO2/Qleg, which led to 9.9% greater O2 extraction. By numerical analysis, the
      increase in Qleg alone (constant DO2) would have raised VO2leg by 35 ml/min
      (mean), but that of DO2 (constant Qleg) would have increased VO2leg by 85 ml/min,
      more than twice as much. The sum of these individual effects (120 ml/min) was
      less (P = 0.013) than the observed rise of 164 ml/min (mean). This synergism
      (explained by the increase in DO2/Qleg) seems to be an important contribution to
      increases in VO2max with training.

PMID- 1400020
TI  - Periodic hemodynamics in skeletal muscle during local arterial pressure
      reduction.
AB  - The time-dependent features of red blood cell flow were evaluated with laser
      Doppler flowmetry (LDF) in the left gastrocnemius muscle of 31 anesthetized New
      Zealand White rabbits during stepwise arterial occlusion. During the control
      period with a median femoral pressure of 72 mmHg, 29 animals showed minor
      irregular fluctuations in LDF blood flow, and only two animals displayed periodic
      variations of blood flow. Lowering femoral arterial pressure induced maximal
      periodic blood flow variations at a median pressure of 35 mmHg in all animals
      with a median frequency of 1.5 cycles/min (termed "slow-wave flow motion"). The
      median amplitude was 48% of the corresponding average flow. These slow waves
      disappeared at a median femoral pressure of 20 mmHg. The median LDF flow value
      was 4.00 arbitrary units (AU) at control pressure and 2.05 AU at maximum slow
      wave flow motion. When slow-wave flow motion was seen at several pressure levels,
      their frequency was identical, which supports the local pacemaker concept. This
      study promotes a novel concept for the role and physiological significance of
      periodic hemodynamics in that it is a condition not characteristic for normal
      control situations but is activated below a specific local arterial blood
      pressure and flow threshold, which is known to be the lower end of autoregulation
      in the microcirculation of rabbit skeletal muscle. This also suggests that slow
      wave flow motion is primarily under local control mechanisms.

PMID- 1400021
TI  - PAF antagonists inhibit pulmonary vascular remodeling induced by hypobaric
      hypoxia in rats.
AB  - Chronic hypoxia causes pulmonary hypertension and pulmonary vascular remodeling
      in rats. Because platelet-activating factor (PAF) levels increase in lung lavage
      fluid and in plasma from chronically hypoxic rats, we examined the effect of two
      specific, structurally unrelated PAF antagonists, WEB 2170 and BN 50739, on
      hypoxia-induced pulmonary vascular remodeling. Treatment with either agent
      reduced hypoxia-induced pulmonary hypertension and right ventricular hypertrophy
      at 3 wk of hypoxic exposure (simulated altitude 5,100 m) but did not affect
      cobalt (CoCl2)-induced pulmonary hypertension. The PAF antagonists had no effect
      on the hematocrit of normoxic or chronically hypoxic rats or CoCl2-treated rats.
      Hypoxia-induced pulmonary hypertension was associated with an increase in the
      vessel wall thickness of the muscular arteries and reduction in the number of
      peripheral arterioles. In WEB 2170-treated rats, these changes were significantly
      less severe than those observed in untreated chronically hypoxic rats. PAF
      receptor blockade had no acute hemodynamic effects; i.e., it did not affect
      pulmonary arterial pressure or cardiac output nor did it affect the magnitude of
      acute hypoxic pulmonary vasoconstriction in awake normoxic or chronically hypoxic
      rats. Isolated lungs from chronically hypoxic rats showed a pressor response to
      the chemotactic tripeptide N-formyl-Met-Leu-Phe (fMLP) and an increase in the
      number of leukocytes lavaged from the pulmonary circulation. In vivo treatment
      with WEB 2170 significantly reduced the fMLP-induced pressor response compared
      with that observed in isolated lungs from untreated chronically hypoxic rats.
      These results suggest that PAF contributes to the development of chronic
      pulmonary hypertension induced by chronic hypoxia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1400023
TI  - Neutral endopeptidase inhibitor potentiates endothelin-1-induced airway smooth
      muscle contraction.
AB  - To study the role of neutral endopeptidase (NEP) on endothelin-1-induced
      contraction of the airway smooth muscle, we examined the contractile effect of
      endothelin-1 in the isolated guinea pig trachea and human bronchus in the
      presence or absence of NEP inhibitor phosphoramidon. After incubation with
      phosphoramidon (10(-8) to 10(-5) M), we added endothelin-1 cumulatively from 10(
      11) to 10(-7) M to the airway tissues in organ baths. Phosphoramidon
      significantly potentiated the endothelin-1-induced contraction in a concentration
      dependent fashion in both guinea pig trachea and human bronchus, and it shifted
      the concentration-response curves to the left. Because NEP is known to cleave
      tachykinins, we next studied whether endothelin-1 contracts airway tissues by
      releasing endogenous tachykinins from bronchial C-fibers. After incubation with
      phosphoramidon (10(-5) M), we added endothelin-1 cumulatively from 10(-11) to 10(
      7) M to the tissues that were treated with capsaicin to deplete the tachykinins.
      Phosphoramidon significantly potentiated the endothelin-1-induced contraction in
      the capsaicin-treated tissues, suggesting that endothelin-1 causes the
      contraction, at least in part, without releasing tachykinins. In contrast to the
      effect of phosphoramidon, captopril (an angiotensin-converting enzyme inhibitor),
      leupeptin (a serine protease inhibitor), and bestatin (an aminopeptidase
      inhibitor) did not modulate the effect of endothelin-1-induced contraction in
      both guinea pig trachea and human bronchus. From these results, we conclude that
      NEP plays an important role in regulating endothelin-1-induced contraction in the
      guinea pig trachea and human bronchus.

PMID- 1400022
TI  - A peptidergic component to vagally induced tracheal vasodilation in the dog.
AB  - The purpose of the study was to determine the extent that peptidergic afferent
      and efferent pathways contribute to vagally induced vasodilation in the trachea
      of the dog. The change in vascular resistance of the tracheal branch of the
      cranial thyroid artery and the trachealis responses were determined in 28
      anesthetized, paralyzed, and mechanically ventilated dogs. After propranolol (2
      mg/kg) and phentolamine (1.5 mg/kg), stimulation of the superior laryngeal nerves
      (NS; 15 Hz, 7 V, 2 ms, 30 s) caused a decrease in vascular resistance of 11.7 +/-
      0.8% and a tracheal contraction of 5.2 +/- 4.7 cmH2O. Atropine (1.5 mg/kg)
      reduced the fall in vascular resistance to 4.7 +/- 0.8% (P less than 0.01),
      whereas tracheal contraction was abolished. Thiorphan (1.5 mg), a neutral
      endopeptidase inhibitor, augmented the decrease in vascular resistance (8.8 +/-
      0.6%; P less than 0.01) to NS. After hexamethonium (0.5 mg/kg), NS still caused a
      small decrease in TVR (2.9 +/- 0.9%; P less than 0.05), which was abolished by
      capsaicin. In atropinized dogs, capsaicin reduced the fall in vascular resistance
      after NS; the residual vasodilation was virtually abolished by hexamethonium.
      Acetylcholine (10(-3) mg/kg) decreased vascular resistance (15.7 +/- 3.0%), and
      the effect was abolished by atropine. We conclude that there is noncholinergic
      nonadrenergic vagally induced tracheal vasodilation that is peptidergic. The
      peptidergic vasodilation appears to be mediated by both afferent and efferent
      pathways.

PMID- 1400024
TI  - Relationship between body and leg VO2 during maximal cycle ergometry.
AB  - It is not known whether the asymptotic behavior of whole body O2 consumption
      (VO2) at maximal work rates (WR) is explained by similar behavior of VO2 in the
      exercising legs. To resolve this question, simultaneous measurements of body and
      leg VO2 were made at submaximal and maximal levels of effort breathing normoxic
      and hypoxic gases in seven trained male cyclists (maximal VO2, 64.7 +/- 2.7 ml
      O2.min-1.kg-1), each of whom demonstrated a reproducible VO2-WR asymptote during
      fatiguing incremental cycle ergometry. Left leg blood flow was measured by
      constant-infusion thermodilution, and total leg VO2 was calculated as the product
      of twice leg flow and radial arterial-femoral venous O2 concentration difference.
      The VO2-WR relationships determined at submaximal WR's were extrapolated to
      maximal WR as a basis for assessing the body and leg VO2 responses. The
      differences between measured and extrapolated maximal VO2 were 235 +/- 45 (body)
      and 203 +/- 70 (leg) ml O2/min (not significantly different). Plateauing of leg
      VO2 was associated with, and explained by, plateauing of both leg blood flow and
      O2 extraction and hence of leg VO2. We conclude that the asymptotic behavior of
      whole body VO2 at maximal WRs is a direct reflection of the VO2 profile at the
      exercising legs.

PMID- 1400026
TI  - Accumulated oxygen deficit increases with inclination of uphill running.
AB  - This study examined whether accumulated oxygen deficit depends on treadmill grade
      during uphill running. Oxygen uptake was measured during steady-state submaximal
      running. By linear extrapolation at each grade, energy demand was estimated for
      short exhaustive runs. Oxygen deficit was the difference between this estimate
      and accumulated oxygen uptake. Six subjects ran at grades of 1, 15, and 20%
      (study I), and five males trained for anaerobic metabolism ran at 1, 10.5, and
      15% (study II). Accumulated oxygen deficit was 40 +/- 11 (SD), 72 +/- 20, and 69
      +/- 8 ml O2/kg, respectively (study I), and 57 +/- 8, 78 +/- 10, and 100 +/- 7 ml
      O2/kg (study II). The finding that accumulated oxygen deficit became larger with
      treadmill inclination could reflect involvement of an increasing muscle mass.
      However, variation in accumulated oxygen deficit was too large to make this
      possibility the only explanation. More likely at small treadmill inclinations
      energy demand for high-intensity running is underestimated by extrapolation from
      oxygen uptake during submaximal exercise. At high grades of uphill running,
      accumulated oxygen deficit reached a maximum that may reflect the subjects'
      anaerobic capacity for running. This hypothesis was substantiated by an enhanced
      accumulated oxygen deficit in the anaerobically trained subjects during 15%, but
      not during 1%, uphill running.

PMID- 1400025
TI  - Bronchomotor vagal preganglionic cell bodies in the dog: an anatomic and
      functional study.
AB  - A previous study in our laboratory demonstrated that the stimulation with
      microinjection of DL-homocysteic acid of cell bodies in the rostral portion of
      the external formation of the nucleus ambiguus (Aext) increased total lung
      resistance in dogs. In the present study anatomic experiments were conducted in
      dogs to determine if the rostral Aext contains vagal preganglionic cell bodies
      that give rise to axons in the pulmonary branches of the vagus nerve. The
      application of horseradish peroxidase (HRP) to either the pulmonary branches or
      the vagus at a point between the pulmonary branches and the cardiac branches
      resulted in retrograde labeling of cell bodies in both rostral Aext and the
      dorsal motor nucleus of the vagus (DMN). On the other hand, application of HRP to
      the vagus at a point below the pulmonary branches did not result in any
      retrogradely labeled cell bodies in rostral Aext but did result in labeled cell
      bodies in DMN. In another series of experiments DL-homocysteic acid (2.5 nmol in
      25 nl) was microinjected at sites in rostral Aext and DMN. As we previously
      reported the injection of DL-homocysteic acid in rostral Aext increased total
      lung resistance. In contrast, in the same animals, the injection of DL
      homocysteic acid in DMN did not change total lung resistance. We conclude that
      bronchomotor vagal preganglionic cell bodies are located in rostral Aext but not
      in DMN. The functional significance of vagal preganglionic cell bodies in DMN
      whose axons contribute to the pulmonary branches of the vagus nerve remains to be
      determined.

PMID- 1400027
TI  - Fatigability and blood flow in the rat gastrocnemius-plantaris-soleus after
      hindlimb suspension.
AB  - The purpose of this study was to test the hypothesis that hindlimb suspension
      increases the fatigability of the soleus during intense contractile activity and
      determine whether the increased fatigue is associated with a reduced muscle blood
      flow. Cage-control (C) and 15-day hindlimb-suspended (HS) rats were anesthetized,
      and either the gastrocnemius-plantaris-soleus (G-P-S) muscle group or the soleus
      was stimulated (100 Hz, 100-ms trains at 120/min) for 10 min in situ. In the G-P
      S preparation, blood flow was measured with radiolabeled microspheres before and
      at 2 and 10 min of contractile activity. The G-P-S fatigued markedly at this
      stimulation frequency, and the differences between C and HS animals were not
      significant until the 9th min of contractile activity. In contrast, the
      stimulation resulted in faster rates and significantly larger amounts of fatigue
      in the soleus from HS than from C animals. The atrophied soleus showed
      significant differences by 1 min of stimulation (C = 70 +/- 1% vs. HS = 57 +/- 2%
      of peak train force) and remained different at 10 min (C = 64 +/- 4% vs. HS = 45
      +/- 2% peak train force). Relative blood flow to the soleus was similar between
      groups before and during contractile activity (rest: C = 20 +/- 3 vs. HS = 12 +/-
      3; 2 min: C = 128 +/- 6 vs. HS = 118 +/- 4; 10 min: C = 123 +/- 11 vs. HS = 105
      +/- 11 ml.min-1.100 g-1). In conclusion, these results established that 15 days
      of HS increased the fatigability of the soleus, but the effect was not caused by
      a reduced muscle blood flow.

PMID- 1400028
TI  - Effects of high-frequency pressure waves applied to upper airway on respiration
      in central apnea.
AB  - We examined the effects of high-frequency (30-Hz) low-pressure oscillations on
      respiration in nine patients with central sleep apnea. All patients were studied
      during sleep and wore a nasal mask through which the oscillations were applied.
      All tests were performed during periods of repetitive central apneas. Respiratory
      efforts were monitored from the airflow and calibrated Respitrace signals. After
      several cycles of apnea were monitored, the oscillatory pressures were applied
      for brief periods (less than 5 s) at the midpoint of the central apneas. All
      trials in which arousal occurred were discarded, leaving a total of 106 trials in
      the nine patients. High-frequency oscillation of the upper airway stimulated
      respiratory effort(s) in 68% of all trials (72 of 106). Apnea length was
      significantly shortened in four of the nine patients. In one patient with a
      tracheostomy, the stimulus applied to his isolated upper airway evoked
      respiratory efforts during central apnea in 13 of 15 trials. We conclude that
      high-frequency oscillatory pressures applied to the upper airway can stimulate
      respiratory efforts during central apnea. This response may be mediated by upper
      airway receptors involved in nonrespiratory airway defense reflexes and may have
      implications in the treatment of patients with central sleep apnea.

PMID- 1400029
TI  - Sensitivity to endotoxin in rabbits is increased after hemorrhagic shock.
AB  - The immunoinflammatory response following trauma and hemorrhage may predispose to
      the development of sepsis and multiple-organ failure syndrome. Cardiac output
      (CO), arterial pressure, arterial PO2, and pulmonary permeability index were
      measured. We examined the sensitivity of rabbits to infusions of
      lipopolysaccharide (LPS) after hemorrhagic shock. Shock was produced by reducing
      CO to 40% of baseline for 90 min, followed by resuscitation with shed blood and
      then with lactated Ringer solution to maintain CO near baseline. Animals were
      assigned to three groups: 1) hemorrhagic shock only, 2) LPS only, and 3)
      hemorrhagic shock + LPS. Groups 1 and 3 were subjected to hemorrhagic shock on
      day 1. Escherichia coli LPS was infused (1.0 microgram/kg i.v.) into groups 2 and
      3 on day 2. Fluid resuscitation with lactated Ringer solution was continued in an
      effort to maintain CO at baseline. Five hours after LPS infusion, 125I-albumin
      was injected intravenously, and rabbits were killed 1 h later for measurement of
      pulmonary permeability index. LPS infusion after shock (group 3) caused
      significant decreases in CO, arterial pressure, and PO2 and an increase in
      pulmonary permeability. These changes were not seen in the groups 1 and 2. We
      conclude that hemorrhagic shock and resuscitation result in a proinflammatory
      state, leading to increased sensitivity to subsequent exposure to LPS.

PMID- 1400031
TI  - Low-dose dopamine hastens onset of gut ischemia in a porcine model of hemorrhagic
      shock.
AB  - Gut metabolism may become anaerobic before the whole body during progressive
      phlebotomy in dogs. Because dopamine has selective mesenteric vasodilator
      effects, we asked whether dopamine could delay onset of bowel ischemia during
      hemorrhagic shock. We studied whole body and gut O2 consumption (VO2) and O2
      delivery (QO2) using progressive phlebotomy in anesthetized pigs. Nine pigs
      received a dopamine infusion of 2 micrograms.kg-1.min-1, whereas a control group
      of seven pigs received equivalent saline infusion. Onset of ischemia in whole
      body and gut was determined as critical O2 delivery (QO2c), the intersection
      point of biphasic regression on plots of VO2-QO2 relationships. Blood flow and O2
      extraction were measured as mechanisms of gut ischemia for entire in situ small
      and large gut using a superior mesenteric venous fistula. Dopamine hastened onset
      of gut ischemia relative to onset of whole body ischemia (gut critical point in
      terms of whole body QO2 9.9 +/- 2.1 ml O2.kg-1.min-1, whole body QO2c 7.8 +/- 0.7
      ml O2.kg-1.min-1, P less than 0.01). In contrast, onset of gut ischemia in
      control animals occurred at same time as onset of whole body ischemia (gut
      critical point in terms of whole body QO2 7.4 +/- 2.3 ml O2.kg-1.min-1, whole
      body QO2c 7.1 +/- 2.7 ml O2.kg-1.min-1, P = not significant). Hastening of onset
      of gut ischemia in dopamine-treated animals was associated with decreased ability
      of gut to extract O2. Low-dose dopamine was not protective against gut ischemia
      during shock but rather caused earlier onset of gut ischemia during hemorrhagic
      shock.

PMID- 1400030
TI  - Short-term reversibility of ultrastructural changes in pulmonary capillaries
      caused by stress failure.
AB  - We previously showed that when the pulmonary capillaries in anesthetized rabbits
      are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress
      failure of the walls occurs with disruption of the capillary endothelium,
      alveolar epithelium, or sometimes all layers. The present study was designed to
      determine whether some of the ultrastructural changes are rapidly reversible when
      the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O
      for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline
      dextran perfusion, followed by intravascular fixation at the same pressure. In
      another group of animals, the pressure was elevated for 1 min of blood and 3 min
      of saline-dextran before being reduced. The results were compared with previous
      studies in which the capillary pressures were maintained elevated at 52.5 cmH2O
      during the entire procedure. Control studies were also done at sustained low
      pressures. The results showed that the number of endothelial and epithelial
      breaks per millimeter and the total fraction area of the breaks were reduced when
      the pressure was lowered. For example, the number of endothelial breaks per
      millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of
      epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was
      evidence that the breaks that closed were those that were initially small and
      were associated with an intact basement membrane. The results suggest that cells
      can move along their underlying matrix by rapid disengagement and reattachment of
      cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1400032
TI  - Relationship among running mileage, bone density, and serum testosterone in male
      runners.
AB  - Our purpose was to investigate the relationship between running volume and bone
      mineral mass in adult male runners. Whole body and regional bone mineral density
      were determined by dual-photon absorptiometry in 22 sedentary controls and 53
      runners who were selected according to their running mileage to fall into a 5- to
      10-, 15- to 20-, 25- to 30-, 40- to 55-, or 60- to 75-mile/wk group. All groups
      were of similar age (20-45 yr) and nutritional status, as determined by 7-day
      food records. Regional sites for bone density measurements included the trunk,
      spine, pelvis, thighs, and lower legs. In addition, serum total testosterone was
      determined in each subject and computed tomography scans were made of the lower
      legs in 34 subjects to assess bone cross-sectional area. No significant
      differences were detected for bone density measurements with the exception of the
      lower legs where it was significantly (P less than 0.05) greater for the 15- to
      20-mile/wk group than for the control and 5- to 10-mile/wk groups. With mileage
      greater than 20 miles/wk, bone density of the lower legs showed no further
      increase and, in fact, tended to decrease, so that for the 60- to 75-mile/wk
      group it was similar to that of the controls. Cross-sectional area of the tibia
      and fibula when normalized to body weight tended to be greater as weekly mileage
      increased and was significantly greater in the 40- to 55-mile/wk runners than in
      the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400033
TI  - Effect of temperature on the biaxial mechanics of excised lung parenchyma of the
      dog.
AB  - The influence of temperature on the mechanical properties of excised saline
      filled lung parenchyma of the dog was studied at low lung volume. The motivation
      of this study was to determine whether lung tissue material without the influence
      of surface tension undergoes a phase transition in the 20-40 degrees C range, as
      does synthetic elastin studied by Urry in 1984-1986. Dynamic biaxial and uniaxial
      tensile tests were done, and strain vs. Lagrangian stress curves were recorded
      during slow cooling and heating between 40 and 10 degrees C. To emphasize the
      effects of elastin, strains (defined as stretch ratio minus one) were kept below
      30%. A slight decrease in compliance occurred with cooling over the entire
      temperature range. This effect may be attributed to collagen. It was accompanied
      by a gradual increase in length as the tissue cooled, an effect that may be
      attributed to elastin. This process was partially reversible with reheating.
      However, this effect is in contrast with the sudden drastic change in mechanical
      properties of synthetic elastin described by Urry. Hysteresis, creep, and stress
      relaxation were small at these low strains. Possible causes of these effects are
      discussed.

PMID- 1400034
TI  - Optimized estimation of respiratory impedance by signal averaging in the time
      domain.
AB  - The spontaneous breathing of a subject during measurements of respiratory
      impedance (Zrs) by the forced oscillation technique (FOT) induces errors that
      result in biased impedance estimates, especially at low frequencies. Although in
      standard measurements this bias may be avoided by using special impedance
      estimators, there are two applications of FOT for which such estimators are not
      useful: when a head generator is used and when measurements are made during
      intubation. In this paper we describe a data-processing procedure for unbiased
      impedance estimation for all FOT setups. The proposed estimator (Z) was devised
      for pseudorandom excitation and is based on time-domain signal averaging before
      frequency analysis. The performance of estimator Z was first analyzed by computer
      simulation of a head generator setup and a setup including an endotracheal tube
      to measure (2-32 Hz) a resistance-inertance-elastance model mimicking Zrs of a
      healthy subject. Second, Z was assessed during real measurements in 16 healthy
      subjects. The results obtained in the simulation (e.g., error in elastance was
      reduced from 15.6% with most conventional estimators to 3.3% with Z in simulation
      of head generator setup) and in the measurements in subjects (differences of less
      than 1.6% between Z and a reference) confirmed the theoretical lack of bias of Z
      and its practical suitability for the different FOT setups. In addition to its
      applicability in the situations in which no other unbiased estimators are
      available, estimator Z is also advantageous in most conventional applications of
      FOT, since it requires much less computing time and thus allows on-line Zrs
      measurements.

PMID- 1400035
TI  - A method for analysis of pulmonary arterial and venous occlusion data.
AB  - Recently, we presented a compartmental model of the pulmonary vascular resistance
      (R) and compliance (C) distribution with the configuration C1R1C2R2C3 (J. Appl.
      Physiol. 70: 2126-2136, 1991). This model was used to interpret the pressure vs.
      time data obtained after the sudden occlusion of the arterial inflow (AO), venous
      outflow (VO), or both inflow and outflow (DO) from an isolated dog lung lobe. In
      the present study, we present a new approach to the data analysis in terms of
      this model that is relatively simple to carry out and more robust. The data used
      to estimate the R's and C's are the steady-state arterial [Pa(0)] and venous
      [Pv(0)] pressures, the flow rate (Q), the area (A2) encompassed by Pa(t) after AO
      and the equilibrium pressure (Pd) after DO, and the average slope (m) of the
      Pa(t) and Pv(t) curves after VO. The following formulas can then be used to
      calculate the 2 R's and 3 C's: [Pa(0) - Pv(0)]/Q = R1 + R2 = RT, R1C1 congruent
      to to A2/[Pa(0) - Pd], R1 congruent to [Pa(0) - Pd]/Q, Q/m = C1 + C2 + C3 = CT,
      and C2 = CT - (RTC1/R2).

PMID- 1400036
TI  - On the purported discovery of the bronchial circulation by Leonardo da Vinci.
AB  - Among modern physiologists and anatomists, there has been a nearly universal
      acceptance that Leonardo da Vinci was the first to identify the anatomy of the
      bronchial circulation. However, because of certain ambiguities in both his
      anatomic drawing that was supposed to have shown this circulation and the
      accompanying descriptive text, we questioned whether he really could have been
      the first to discover this small but important vasculature. To address this
      question, we set out to repeat Leonardo's dissections in the ox. We reasoned that
      perhaps the normally tiny bronchial vessels would be considerably more noticeable
      in this very large species. Our dissections, however, failed to provide any
      evidence that Leonardo's drawing was that of the bronchial circulation.
      Furthermore we observed a set of distinct small pulmonary veins to the left upper
      and right middle lobes that Leonardo, given his lack of understanding of the
      function of the lung and its circulation, could have easily mistaken for a
      separate circulation. We thus conclude that Leonardo da Vinci did not describe
      the anatomy of the bronchial circulation. We believe that the first person to
      clearly and unequivocally describe the anatomy of this circulation was the Dutch
      Professor of Anatomy and Botany, Frederich Ruysch.

PMID- 1400037
TI  - Hypoxic bronchodilation.
AB  - Recent advances in computed tomographic imaging provide a unique method to
      serially and directly visualize acute physiological response in the lung. To
      directly investigate the airway response to hypoxia, high-resolution computed
      tomographic scans of the lungs of eight intact anesthetized minipigs were
      serially repeated before, during, and after ventilation with a hypoxic gas
      mixture (inspired fraction of O2 congruent to 0.07). This approach demonstrated
      an acute reversible 56 +/- 8% (SE) dilation in large airways (greater than 2 mm
      diam) and a 90 +/- 15% dilation in small airways (less than 1.99 mm diam) with
      decreased inspired O2 tension. Of the airways studied, 70 of 76 dilated. Hypoxic
      bronchodilation may interact with hypoxic pulmonary vasoconstriction in the
      fundamental physiological process of ventilation-perfusion matching in the lung.

PMID- 1400038
TI  - Is the O2 deficit an accurate quantitative measure of the anaerobic energy
      production during intense exercise?

PMID- 1400039
TI  - Intrinsic properties of pharyngeal and diaphragmatic respiratory motoneurons and
      muscles.
AB  - Breathing is a complex act requiring the coordinated activity of multiple groups
      of muscles. Thoracic and abdominal respiratory muscles expand and contract the
      lungs, whereas pharyngeal and laryngeal respiratory muscles maintain upper airway
      patency and regulate upper airway resistance. An appreciation of the importance
      of the latter muscle group in maintaining ventilatory homeostasis and in the
      pathophysiology of sleep apnea has led to extensive studies examining the neural
      regulation of pharyngeal dilator muscles. The present review examines the role of
      heterogeneity in motoneuron and muscle properties in determining the diversity in
      the electrical and mechanical behaviors of thoracic compared with pharyngeal
      muscle groups. Specifically, phrenic and hypoglossal motoneuron
      electrophysiological properties influence whether and the extent to which these
      neurons will fire in response to a given synaptic input arising from chemo- and
      mechanoreceptors and from respiratory and nonrespiratory pattern generators.
      Furthermore, thoracic and pharyngeal muscle properties determine the mechanical
      response to motoneuronal activity, including the speed of contraction,
      relationships between motoneuron firing frequency and force production, and
      whether force is maintained during repetitive activation. Heterogeneity in the
      functional capabilities of these motoneurons and muscles is in turn determined by
      diversity of their structural and biochemical properties. Thus, intrinsic
      properties of respiratory motoneurons and muscles act in concert with neuronal
      drives in defining the complex electrical and mechanical behavior of pharyngeal
      and thoracic respiratory motor systems.

PMID- 1400040
TI  - Effects of growth hormone on diaphragmatic recovery from malnutrition.
AB  - A 25% weight loss was induced in adult Fisher 344 rats by nutritional
      deprivation. Subsequently, normal feeding was resumed. Refed animals were divided
      into three groups and received recombinant human growth hormone (rhGH) injections
      during 5 wk of refeeding, saline injections during 5 wk of refeeding, or 9 wk of
      refeeding without injections. The effects of nutritional deprivation and the
      various refeeding protocols on the cross-sectional areas (CSA) of each of the
      four types of myofibers [typed immunohistochemically with antibodies against four
      myosin heavy chain (MHC) isoforms known to be present in the rat diaphragm] were
      determined. Malnutrition decreased the CSA of myofibers containing MHC2X, MHC2B,
      and MHC2A (i.e., fast myofibers), with the greatest effect on muscle mass being
      due to the atrophy of fibers containing MHC2X. Fibers containing MHC beta/slow
      failed to undergo malnutrition-induced atrophy. Whereas refeeding for 5 wk in the
      absence of rhGH allowed the recovery of CSA of fibers containing MHC2A, fibers
      containing MHC2B and MHC2X remained smaller than fibers of similar type in
      control animals. In contrast, 5 wk of refeeding supplemented with rhGH returned
      all fiber CSAs to control values. Even when refeeding alone was extended to 9 wk
      to allow for weight stabilization, the CSA of the fibers containing MHC2B and
      MHC2X remained smaller than similar fibers in control muscle. Serum insulin-like
      growth factor, a marker of malnutrition (R. Reeves and J. Elders, J. Nutr. 109:
      613-620, 1979), was significantly decreased after nutritional deprivation and
      returned to normal after 5 wk of refeeding and GH supplementation.

PMID- 1400041
TI  - Differences in metabolic response of dog and goat latissimus dorsi muscle to
      chronic stimulation.
AB  - The latissimus dorsi (LD) muscle is considered suitable to assist ventricular
      mechanical function in either cardiomyoplasty or extra-aortic-assist devices.
      Such application requires that this mixed-type skeletal muscle be transformed
      into a fatigue-resistant muscle, the adaptation of which can be elicited by
      chronic stimulation. In this study the LD muscles of dog and goat were subjected
      in situ to 12 wk of continuous electrical stimulation through intramuscular
      electrodes, and their myofibrillar and metabolic adaptations were compared. A
      gradual increase in the contraction rate of the muscle (in 10 wk from 30 to 80
      contractions/min) caused the proportion of immunohistochemically identified type
      I fibers to increase in dog muscle from 30 to 74% and in goat muscle from 21 to
      99%. Correspondingly, the anaerobic-glycolytic activity (fructose-6-phosphate
      kinase and lactate dehydrogenase activities) decreased by approximately 75% in
      both dog and goat muscles, whereas the oxidative capacity (fatty acid oxidation
      and citrate synthase activity) increased two- to threefold in goat LD muscle but
      remained unaltered in dog LD muscle. Muscular contents of high-energy phosphates
      and endogenous substrates were maintained, but the L-carnitine content decreased
      by 43% in both dog and goat. Our data further indicate that, for the monitoring
      of the metabolic adaptation of skeletal muscle, the ratio of activities of the
      oxidative and anaerobic-glycolytic pathways (e.g., citrate synthase to fructose-6
      phosphate kinase activities) is a useful parameter in both dog and goat.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1400042
TI  - Compensatory muscle fiber hypertrophy in elderly men.
AB  - Muscle strength and muscle morphology have been studied three times during a
      period of 11 yr in nine elderly men. On the last occasion the average age was
      80.4 (range 79-82) yr. Body cell mass decreased by 6% and muscle strength for
      knee extension, measured by means of isometric and concentric isokinetic (30-60
      degrees/s) recordings, declined by 25-35% over the 11-yr period. Between 76 and
      80 yr of age only the isokinetic strength for 30 degrees/s decreased
      significantly. Muscle fiber composition in the vastus lateralis did not change
      between 69 and 76 yr of age, but there was a significant reduction in the
      proportion of type IIb fibers from 76 to 80 yr. The decrease in type II fiber
      areas was not significant between 69 and 76 yr of age (as in a larger sample from
      the same population), but a significant increase in both type I and type II fiber
      areas was recorded from 76 to 80 yr of age and biceps brachii showed similar
      tendencies. In the same period, the enzymatic activities of myokinase and lactate
      dehydrogenase subsided in the vastus lateralis, but there was no change for
      triose phosphate dehydrogenase, 3-hydroxy-CoA-dehydrogenase, and citrate
      synthase. The muscle fiber hypertrophy in this group of elderly men with
      maintained physical activity between 76 and 80 yr of age is interpreted as a
      compensatory adaptation for the loss of motor units. In addition, the adaptation
      with respect to oxidative capacities seems to be maintained at this age.

PMID- 1400043
TI  - Distribution of injury and microdosimetry of ozone in the ventilatory unit of the
      rat.
AB  - The distribution of ozone-induced injury across ventilatory units of the lungs
      was determined and compared with the predicted distribution of ozone dose across
      the same units to evaluate dose-response relationships. Sprague-Dawley rats were
      exposed to either 0.98 ppm ozone 8 h/day for 90 days or to filtered air only. En
      bloc microdissection was used to identify and isolate in longitudinal profile the
      bronchiole-alveolar duct junction, first pair of alveolar duct generations, and
      intervening bifurcation ridge. The first alveolar outpocketing along the
      bronchiolar wall of each isolation was used to identify the center of a series of
      concentric arcs radiating outward at 100-microns intervals across each
      ventilatory unit. The intercept lengths of each arc with the tissue of alveolar
      septal tips (edges) and alveolar walls were measured and expressed as a function
      of distance into the ventilatory unit. Relative ozone dose across the ventilatory
      unit was estimated using the geometry of the tracheobronchial tree and the volume
      and surface area distribution within individual ventilatory units. This
      mathematical model of ozone dose demonstrated a high degree of correlation to
      this measured tissue injury response. The findings of this study demonstrate that
      microdosimetry and microtoxicology can be used to determine dose-response
      relationships within the ventilatory unit and to assess questions of tissue
      sensitivity in ozone-induced lung injury.

PMID- 1400044
TI  - Oxygen cost of resistive-loaded breathing in quadriplegia.
AB  - We hypothesized that, in quadriplegia, chest wall distortion would increase the
      energy cost of ventilation. To assess this, we measured the oxygen cost of
      breathing (VO2 resp) and changes in chest wall configuration during inspiratory
      resistive-loaded breathing tasks in five quadriplegic and five normal subjects.
      Each subject performed three breathing tasks that spanned a range of work rates
      (Wtot). Configurational changes of the abdomen and upper, lower, and transverse
      rib cage were assessed with magnetometers. We found that 1) in both groups,
      VO2resp increased linearly with Wtot over the range of tasks performed, 2) the
      mean slope of the regression line of VO2resp vs. Wtot was greater for
      quadriplegic than for normal subjects (3.7 +/- 0.8 vs. 2.0 +/- 0.7 ml O2/J, P
      less than 0.01), 3) efficiency of breathing (Wtot/VO2resp) was less for
      quadriplegic than for normal subjects (1.9 +/- 0.6 vs. 3.5 +/- 1.4%, P less than
      0.001), 4) during inhalation, upper and lower rib cages behaved similarly in the
      two groups, but the quadriplegic subjects had a decrease in transverse rib cage
      and a much greater increase in abdomen than normal subjects, and 5) functional
      residual capacity decreased in normal but not in quadriplegic subjects during the
      breathing tasks. We conclude that the lesser efficiency of breathing in
      quadriplegia may be related to the elastic work of chest wall distortion, shorter
      mean operational diaphragm length, and possibly differences between normal and
      quadriplegic subjects in mechanical advantage of available inspiratory muscles.

PMID- 1400045
TI  - Decrease in lung volume-related feedback enhances laryngeal reflexes to negative
      pressure.
AB  - Negative pressure applied to the upper airway has an excitatory effect on the
      activity of upper airway muscles and an inhibitory effect on thoracic inspiratory
      muscles. The role of lung volume feedback in this response was investigated in 10
      anesthetized spontaneously breathing adult rabbits. To alter lung volume
      feedback, the lower airway was exposed to SO2 (250 ppm for 15 min), thereby
      blocking slowly adapting receptors (SARs). Negative pressure pulses (5, 10, and
      20 cmH2O, 300-ms duration) were applied to the functionally isolated upper airway
      before and after SAR blockade. Tracheal airflow and electromyogram (EMG) of the
      genioglossus and alae nasi were recorded. Peak EMG, peak inspiratory flow, tidal
      volume, and respiratory timing of control breaths (3 breaths immediately
      preceding test) and test breaths were determined. Analysis of variance was used
      to determine the significance of the effects. Negative pressure pulses increased
      peak EMG of genioglossus and alae nasi and inspiratory duration and decreased
      peak inspiratory flow. These effects were larger after SAR blockade. We conclude
      that a decrease in volume feedback from the lung augments the response to upper
      airway pressure change.

PMID- 1400046
TI  - Erythropoietin response to acute normobaric hypoxia in humans.
AB  - Hypoxia causes an increased production of erythropoietin (EPO), but the time
      course of the EPO response in humans has not been well characterized. This study
      examines the relationship between the duration of normobaric hypoxic exposure and
      plasma EPO levels in healthy human subjects. Six volunteers breathed a gas
      mixture of 10.5% O2-89.5% N2 continuously for 5, 60, and 120 or intermittently
      for 240 min. O2 saturations were maintained between 75 and 85% during the
      exposure. Arterial pH was 7.467 +/- 0.019, PO2 37.05 +/- 2.43 Torr, and PCO2
      36.69 +/- 2.05 Torr. O2 half-saturation pressures of hemoglobin were normal for
      all subjects. Plasma EPO was measured every 30 min for 360 min by
      radioimmunoassay. No increase in EPO was seen after the 5- and 60-min exposures.
      However, a 50% increase was seen 240 min after the initiation of the 120-min
      hypoxic exposure (P less than 0.01). Intermittent exposure resulted in an
      increase of EPO by 52% 360 min after the onset of exposure (P less than 0.05).
      Therefore, exposing humans continuously to an inspiratory O2 fraction of 0.105
      for 120 min or intermittently for 240 min provides a sufficient stimulus to
      increase production of EPO.

PMID- 1400047
TI  - Late potentials in an ovine model of acute transmural myocardial infarction.
AB  - The development of slow conduction during the first hours of acute transmural
      myocardial infarction (ATMI) was studied by signal-averaged electrocardiograms
      (SAE) in 19 adult anesthetized sheep. SAEs were recorded before and after
      intravenous infusions of lidocaine and bretylium were begun and 10, 30, and 60
      min after ATMI produced by ligation of the left anterior descending and second
      diagonal coronary arteries. Four sheep died promptly of ventricular
      tachyarrhythmias; two others developed sustained ventricular arrhythmias, which
      precluded additional data. Biphasic changes in QRS duration, root mean square
      voltage of the terminal 40 ms of the QRS complex, and duration of terminal low
      amplitude (less than 30 microV) signal were observed. Peak changes in conduction
      occurred 30 min after infarction and regressed toward baseline thereafter. At 30
      min, all animals developed late potentials, which were defined as signals that
      exceeded both after-drug QRS duration and duration of terminal low-amplitude
      signal less than 30 microV by more than two standard deviations. At 60 min, only
      3 of 13 (23%) animals had late potentials. Conduction is slowest 30 min after
      ATMI in sheep but may not be related to development of ventricular arrhythmias.
      In five of six sheep (83%), ventricular arrhythmias occurred within 15 min of
      infarction before peak slowing was observed by SAE.

PMID- 1400048
TI  - Ventilatory and metabolic responses to cold and hypoxia in intact and carotid
      body-denervated rats.
AB  - The effects of hypoxia on thermoregulation and ventilatory control were studied
      in conscious rats before and after carotid denervation (CD). Measurements of
      metabolic rate (VO2), ventilation (V), shivering intensity (SI), and colonic
      temperature (Tc) were made in groups of eight rats subjected to three protocols.
      In protocols 1 and 2, at ambient temperature (Ta) of 25 and 5 degrees C,
      respectively, rats were exposed to normoxia and hypoxia [inspired O2 fraction
      (FIO2) 0.13-0.11]. In protocol 3, Ta was decreased from 25 to 5 degrees C in 30
      min steps of 5 degrees C. Recordings were made in normoxia and hypoxia (FIO2
      0.12). The results show that in both intact and CD rats 1) in normoxia, cold
      exposure increased VO2, V, and SI, and these increases were proportional to the
      decrease in Ta; 2) hypoxia induced only a transient decrease in SI, and, for a
      given Ta, VO2 was reduced whereas V and SI were increased; and 3) in CD rats, V
      increased less during cold exposure in both normoxia and hypoxia; VO2 and Tc were
      more depressed during hypoxia. It is concluded that 1) the interaction between Ta
      and FIO2 in the control of V is partly dependent on the carotid body afferents,
      2) shivering thermogenesis may be transiently affected by hypoxia independently
      of the carotid body afferents, and 3) nonshivering thermogenesis may be directly
      inhibited by hypoxia, especially during cold exposure.

PMID- 1400049
TI  - Relative contribution of bronchial flow to subpleural region in dog lung.
AB  - The bronchial flow is approximately 1% of the total pulmonary flow. Anastomosis
      between the bronchial and pulmonary vessels occurs primarily at the
      microcirculatory level. It is assumed that bronchopulmonary anastomoses are
      present in a homogeneous manner throughout lung parenchyma. To investigate this
      issue, an in situ blood-perfused left lower lung lobe (500 ml/min) was prepared
      in a live dog. The bronchial flow rate in the entire lobe was monitored using the
      rate of volume gain in the reservoir while the pulmonary and bronchial flow in
      the subpleural region was monitored using laser-Doppler flowmetry. The results
      were expressed as ratio of bronchial to pulmonary flow rate for the entire lobe
      and for the subpleural region. We found that, for the entire lobe, bronchial flow
      was 1.0% of pulmonary flow, while for the subpleural region this ratio was much
      higher, with an average of 12%. In two different experimental conditions that
      were imposed to affect the global bronchial flow, these ratios changed in the
      same direction as the global bronchial flow. After transfusion of blood into the
      animal, bronchial flow increased to 1.7%, while the subpleural bronchial flow
      increased to 18% of the subpleural pulmonary flow. During elevation of venous
      pressure, bronchial flow decreased to 0.6%, while the subpleural bronchial flow
      decreased to 10% of the subpleural pulmonary flow. The differences in the ratios
      between the global and subpleural region may be explained by having low pulmonary
      blood flow in the periphery compared with the interior regions of the
      lung.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400050
TI  - Aerosol bolus dispersion and convective mixing in human and dog lungs and
      physical models.
AB  - The dispersion of aerosol boluses in the lung is a probe for convective mixing
      and has been proposed as a marker for abnormal lung function. To better
      understand the factors underlying this phenomenon, aerosol dispersion was
      compared in human subjects, dogs, and various physical models. In all systems,
      dispersion increased with the volumetric penetration of the aerosol bolus. The
      rate of this increase was 83% greater in humans compared with dogs. Dispersion in
      dogs was close to that in a packed bed with beads of 2.5 mm. Aerosol dispersion
      decreased with increasing flow rate in human subjects. An artificial larynx
      inserted into the straight tube caused a 33% increase in dispersion. In humans,
      aerosol dispersion was significantly correlated with forced expired flow between
      25 and 75% of vital capacity. A 2-s pause between inspiration and expiration
      increased dispersion 23-58% in three isolated dog lungs but did not affect
      dispersion in the packed bed. The data suggest that lung geometry, flow rate,
      particle mobility, and the larynx all significantly affect aerosol dispersion by
      influencing the reversibility of aerosol transport between inspiration and
      expiration.

PMID- 1400051
TI  - Mechanical constraints on exercise hyperpnea in endurance athletes.
AB  - We determined how close highly trained athletes [n = 8; maximal oxygen
      consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits
      for generating expiratory airflow and inspiratory pleural pressure during maximal
      short-term exercise. Mechanical limits to expiratory flow were assessed at rest
      by measuring, over a range of lung volumes, the pleural pressures beyond which no
      further increases in flow rate are observed (Pmaxe). The capacity to generate
      inspiratory pressure (Pcapi) was also measured at rest over a range of lung
      volumes and flow rates. During progressive exercise, tidal pleural pressure
      volume loops were measured and plotted relative to Pmaxe and Pcapi at the
      measured end-expiratory lung volume. During maximal exercise, expiratory flow
      limitation was reached over 27-76% of tidal volume, peak tidal inspiratory
      pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume
      averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were
      generally reached coincident with the achievement of VO2max; the greater the
      ventilatory response, the greater was the degree of mechanical limitation. Mean
      arterial blood gases measured during maximal exercise showed a moderate
      hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened
      alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of
      hypoxemia (arterial PO2 = 78 Torr, range 65-83 Torr). Increasing the stimulus to
      breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 =
      65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory
      pressure, or expiratory pressure. We conclude that during maximal exercise,
      highly trained individuals often reach the mechanical limits of the lung and
      respiratory muscle for producing alveolar ventilation. This level of ventilation
      is achieved at a considerable metabolic cost but with a mechanically optimal
      pattern of breathing and respiratory muscle recruitment and without sacrifice of
      a significant alveolar hyperventilation.

PMID- 1400052
TI  - Breathing patterns during varied activities.
AB  - The level of ventilation attained and breathing patterns adopted during activity
      have important implications for the distribution and deposition of particles that
      are inhaled. However, breathing patterns and levels of ventilation adopted during
      specific physical activities are unknown. We used a noninvasive means of
      measuring ventilation in subjects performing a variety of activities (bicycling,
      arm ergometry, lifting, and pulling) during unencumbered (no mouthpiece)
      breathing and while breathing through a mouthpiece. Minute ventilation (VE),
      tidal volume (VT), inspiratory time (TI), and total breathing cycle time (TT)
      were measured initially both spirometrically and from body surface displacements.
      When a mouthpiece was used, VE and breathing patterns were significantly altered
      during all activities such that VE, VT, and TT increased by 16, 34, and 20%,
      respectively. This mouthpiece effect was attenuated at the higher levels of VE. A
      task dependency of breathing pattern was also noted such that there was much
      greater variability of VT and TI for a given VE during the lifting activity
      compared with bicycling (coefficient of variation for VT of 0.39 +/- 0.09 vs.
      0.20 +/- 0.07, P less than 0.01; and for TI of 0.38 +/- 0.08 vs. 0.21 +/- 0.08, P
      less than 0.01). We conclude that a mouthpiece significantly alters breathing
      pattern during varied types and intensities of activities, and breathing patterns
      may differ significantly from one activity to another. When the total dose of
      particulates inhaled in the lung are assessed, the mouthpiece effect and activity
      effect on breathing pattern must be considered.

PMID- 1400053
TI  - Changes in afferent and efferent phrenic activities with electrically induced
      diaphragmatic fatigue.
AB  - In anesthetized artificially ventilated cats, diaphragmatic fatigue was produced
      by direct muscle stimulation with trains of pulses for 30 min. Failure of
      contraction was assessed from decrease in the maximal relaxation rate of
      transdiaphragmatic pressure twitches. Motor activities (electromyogram and motor
      phrenic neurogram) were processed by fast-Fourier transform analysis, which
      provided the power spectrum density function (PSDF). The discharge frequency of
      diaphragmatic afferents was also measured. In control conditions (before
      fatigue), intra-arterial bolus injection of lactic acid enhanced tonically active
      diaphragmatic afferents, whereas it reduced the firing rate of afferent fibers
      activated in phase with diaphragmatic contraction or relaxation. The same sensory
      response pattern was observed with the development of diaphragmatic fatigue.
      Leftward shift in PSDFs of motor phrenic neurogram also occurred, but it preceded
      the failure of diaphragmatic contraction as well as the changes in the
      electromyogram's PSDF and afferent paths, which were closely associated with
      lengthening of both inspiratory and total breath durations. After section of the
      phrenic nerves, the motor phrenic response disappeared during the fatigue trial.
      This demonstrates the existence of complex reflex-induced changes in the
      ventilatory control during diaphragmatic fatigue. They seem to involve the
      participation of several types of phrenic afferents.

PMID- 1400054
TI  - Fluid ingestion during exercise increases skin blood flow independent of
      increases in blood volume.
AB  - The purpose of this experiment was to determine whether fluid ingestion
      attenuates the hyperthermia and cardiovascular drift that occurs during exercise
      dehydration due to increases in blood volume. In addition, forearm blood flow,
      which is indicative of skin blood flow, was measured to determine whether the
      attenuation of hyperthermia and cardiovascular drift during exercise with fluid
      ingestion is due to higher skin blood flow. On three different occasions, seven
      trained cyclists [mean age, body weight, and maximum oxygen uptake: 23 +/- 3 yr,
      73.9 +/- 10.5 kg, and 4.75 +/- 0.34 (SD) l/min, respectively] cycled at a power
      output equal to 62-67% maximum oxygen uptake for 2 h in a warm environment (33
      degrees C, 50% relative humidity, wind speed 2.5 m/s). During exercise, they
      randomly received no fluid (NF) or a volume of a carbohydrate-electrolyte fluid
      replacement solution (FR) sufficient to replace 80 +/- 2% of sweat loss or were
      intravenously infused with 5.3 ml/kg of a blood volume expander (BVX; 6% dextran
      in saline). The infusion of 398 +/- 23 ml of BVX maintained blood volume at
      levels similar to that when 2,404 +/- 103 ml of fluid were ingested during FR and
      greater than that when no fluid was ingested during the 2nd h of exercise (P less
      than 0.05). However, BVX and NF resulted in similar esophageal and rectal
      temperatures, forearm blood flow, and elevations in serum osmolality and sodium
      concentration during 2 h of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400055
TI  - Adaptations in coactivation after isometric resistance training.
AB  - Twenty sedentary male university students were randomly assigned to an
      experimental or a control group. The experimental group trained the knee
      extensors of one leg by producing 30 isometric extension maximal voluntary
      contractions (MVC) per day, three times per week for 8 wk. After 8 wk of
      training, extensor MVC in the trained leg increased 32.8% (P less than 0.05), but
      there was no change in vastus lateralis maximal integrated electromyographic
      activity (IEMGmax). The most important finding was that the degree of hamstring
      coactivation during extension MVC decreased by approximately 20% (P less than
      0.05) after the 1st wk of training. Less pronounced adaptations occurred in the
      untrained leg: extension MVC force increased 16.2% (P less than 0.05), hamstring
      coactivity decreased 13% (P less than 0.05) after 2 wk of training, and vastus
      lateralis IEMGmax was unchanged. The same measures in legs of the control group
      were not changed during the study. There were no changes in flexion MVC, biceps
      femoris IEMGmax, or the degree of quadriceps coactivity during flexion MVC in
      either leg of the control or experimental group. A reduction in hamstring
      coactivity in the trained and untrained legs indicates that these muscles provide
      less opposing force to the contracting quadriceps. We conclude that this small
      but significant decrease in hamstring coactivation that occurs during the early
      stages of training is a nonhypertrophic adaptation of the neuromuscular system in
      response to static resistance training of this type.

PMID- 1400056
TI  - Technique-dependent variations in cerebral microvessel blood volumes and
      hematocrits in the rat.
AB  - To quantitate small parenchymal microvessel blood volumes in the brain, the
      distribution spaces of radiolabeled red blood cells (RBC) and serum albumin
      (RISA) were assessed in rats by different methods of tissue sampling and
      radioassay. Three minutes after intravenous administration of 55Fe-RBCs and/or
      125I-RISA, the rats were decapitated. The brain was either immediately frozen
      within the skull and later removed (head-frozen group) or rapidly removed from
      the skull and then frozen (brain-frozen group). Radioactivity was measured either
      by liquid scintillation counting of tissue pieces, which contained pial plus
      large and small parenchymal microvessels, or by quantitative autoradiography
      (QAR) of tissue sections, which indicated small parenchymal microvessel blood
      only. In 12 of 15 areas, the RISA, RBC, and blood volumes determined by liquid
      scintillation counting of head-frozen tissue pieces were equal to or greater than
      those of brain-frozen tissue; this indicated less than or equal to 25% greater
      blood retention in pial and parenchymal microvessels with head freezing. At the
      parenchymal microvessel level (QAR assay), the distribution volumes of RBCs,
      RISA, and blood were similar with the two freezing techniques; hence with QAR
      either freezing procedure can be used to assess small parenchymal microvessel
      blood volumes.

PMID- 1400057
TI  - Effects of ibuprofen and pentoxifylline on the cardiovascular response of normal
      humans to endotoxin.
AB  - Endotoxin is a major mediator of the life-threatening cardiovascular dysfunction
      that characterizes Gram-negative sepsis. In animal models of endotoxemia,
      pretreatment with ibuprofen or pentoxifylline attenuates some of these
      cardiovascular changes. To evaluate the effects of these agents on the human
      cardiovascular response to endotoxemia, hemodynamic variables were measured
      serially in 24 normal subjects who were given intravenous endotoxin. The subjects
      were randomized to receive oral ibuprofen (n = 9), pentoxifylline (n = 10), or no
      medication before endotoxin administration (n = 5). The subjects were volume
      loaded 3-5 h after endotoxin administration, and hemodynamic measurements were
      reassessed. Core temperature after endotoxin alone or endotoxin-pentoxifylline
      approached a maximum at 3 h (greater than or equal to 38.6 degrees C), while the
      endotoxin-ibuprofen group remained afebrile. At 3 and 5 h, all three groups had
      significant increases in heart rate, cardiac index, oxygen delivery, and oxygen
      consumption, while systemic vascular resistance index decreased significantly
      from baseline. The oxygen extraction ratio remained unchanged. After volume
      loading, the left ventricular ejection fraction and left ventricular end
      diastolic and end-systolic volume indexes did not differ among the groups. The
      hyperdynamic cardiovascular response to endotoxin in humans occurs in the absence
      of fever and is not significantly ameliorated by oral cyclooxygenase or
      phosphodiesterase inhibition.

PMID- 1400059
TI  - Use of arterialized venous blood sampling during incremental exercise tests.
AB  - Close agreement between arterialized venous and arterial pH, PCO2, and lactate
      has previously been demonstrated during steady-state exercise. The purpose of the
      present study was to compare arterialized venous and arterial pH, PCO2, K+,
      lactate, pyruvate, and epinephrine during the constantly changing circumstances
      of an incremental exercise test. Eight normal subjects undertook an incremental
      exercise test (increasing by 20 W/min) to exhaustion on a cycle ergometer during
      which simultaneous arterial and arterialized venous samples were drawn over the
      last 20 s of each work load. Linear regression of arterialized venous on arterial
      values showed that r varied from 0.97 to 0.99 for the variables examined and,
      therefore, showed that accurate estimates of arterial values could be made from
      the arterialized venous results during incremental testing. For many purposes it
      could be assumed that arterialized venous values equaled arterial values without
      serious error.

PMID- 1400058
TI  - Vasopressin inhibits diuresis induced by water immersion in humans.
AB  - We tested the hypothesis that 1-desamino-8-D-arginine vasopressin (DDAVP), a V2
      receptor agonist, could inhibit the diuresis induced by water immersion in
      humans. Water and electrolyte excretion, plasma atrial natriuretic factor
      concentration, and plasma aldosterone concentration were measured initially and
      after 3 h of water immersion in 13 healthy sodium-replete men given either
      placebo or 20 micrograms of intranasal DDAVP. Guanosine 3',5'-cyclic
      monophosphate and urea excretion and urine osmolality were also determined. DDAVP
      inhibited the diuresis induced by water immersion in men: 758 +/- 168 (SE) ml/3 h
      in the placebo group vs. 159 +/- 28 ml/3 h in the DDAVP group (P less than 0.05).
      After 3 h of water immersion, plasma atrial natriuretic factor concentrations
      were increased from 11 +/- 2 to 20 +/- 4 pg/ml in the placebo group and from 14
      +/- 2 to 33 +/- 4 pg/ml in the DDAVP group (P less than 0.05). Plasma aldosterone
      concentrations were decreased from 98 +/- 18 to 45 +/- 6 pg/ml in the placebo
      group (P less than 0.05) and from 54 +/- 17 to 25 +/- 5 pg/ml in the DDAVP group
      (P less than 0.05). Despite these changes in aldosterone and atrial natriuretic
      factor concentrations, which should increase sodium excretion, DDAVP decreased
      the natriuresis induced by water immersion in humans: 56 +/- 8 meq Na+/3 h in the
      placebo group vs. 36 +/- 6 meq Na+/3 h in the DDAVP group (P less than 0.05).
      DDAVP may be used to prevent the diuresis associated with central redistribution
      of blood volumes that occur during water immersion.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1400061
TI  - Rib cage shape and motion in microgravity.
AB  - We studied the effect of microgravity (0 Gz) on the anteroposterior diameters of
      the upper (URC-AP) and lower (LRC-AP) rib cage, the transverse diameter of the
      lower rib cage (LRC-TR), and the xiphipubic distance and on the electromyographic
      (EMG) activity of the scalene and parasternal intercostal muscles in five normal
      subjects breathing quietly in the seated posture. Gastric pressure was also
      recorded in four subjects. At 0 Gz, end-expiratory LRC-AP and xiphipubic distance
      increased but LRC-TR invariably decreased, as did end-expiratory gastric
      pressure. No consistent effect was observed on tidal LRC-TR and xiphipubic
      displacements, but tidal changes in URC-AP and LRC-AP were reduced. Although
      scalene and parasternal phasic inspiratory EMG activity tended to decrease at 0
      Gz, both muscle groups demonstrated an increase in tonic activity. We conclude
      that during brief periods of weightlessness 1) the rib cage at end expiration is
      displaced in the cranial direction and adopts a more circular shape, 2) the tidal
      expansion of the ventral rib cage is reduced, particularly in its upper portion,
      and 3) the scalenes and parasternal intercostals generally show a decrease in
      phasic inspiratory EMG activity and an increase in tonic activity.

PMID- 1400060
TI  - Phospholipases introduced into the hypophase affect the surfactant film outlining
      a bubble.
AB  - The hypophase exchanger is a recently developed device that makes it possible to
      replace the liquid in the sample chamber of a pulsating bubble surfactometer,
      after a bubble has been formed, without changing the size of the bubble. A
      surfactant film outlining the bubble will retain its surface properties, provided
      the liquid entering the sample chamber and replacing the hypophase is inert. If,
      on the other hand, the new hypophase consists of a phospholipase solution, the
      physical properties of the film are seriously affected. It was found that when
      phospholipase C, even at low concentration, entered the sample chamber, the
      physical properties were significantly changed. Phospholipase A2 had to be added
      at a higher concentration to exert a similar effect. It is postulated that the
      site of action of phospholipase A2 may be partly protected in the hydrophobic
      region of the tightly packed surfactant film.

PMID- 1400062
TI  - Prolonged pulmonary hypertension caused by platelet-activating factor and
      leukotriene C4 in the rat lung.
AB  - Platelet-activating factor (PAF) and leukotrienes (LTs) are potent pulmonary
      hypertensive and inflammatory mediators produced by the lung. Previously we
      showed that a rapid injection of PAF into the pulmonary artery of an isolated rat
      lung produced an extended elevation in mean pulmonary arterial pressure (PAP).
      The objective of the present study was to determine whether the extended pressor
      response induced by PAF was caused by prolonged activation of the 5-lipoxygenase
      pathway or slow clearance of LTs from the lung parenchyma. Rat lungs were
      perfused with a nonrecirculating physiological salt solution that contained
      indomethacin and albumin. Five minutes after a rapid injection of PAF into the
      pulmonary artery catheter, the following elevations (mean % above baseline) were
      observed: PAP (83%), LTB4 (3,260%), LTC4 (1,490%), LTD4 (970%), and LTE4
      (1,500%). At 20 min these levels declined but were still significantly elevated
      above baseline. The 5-lipoxygenase inhibitor diethylcarbamazine (DEC),
      administered before the PAF injection, inhibited the elevations of PAP and all
      LTs. DEC administration that began 5 min after PAF reduced PAP and only LTC4
      levels at 20 min in comparison to lungs with no DEC. The 5-lipoxygenase
      activating protein inhibitor MK886, administered orally 2-6 h before perfusion,
      also inhibited the pressor response to PAF as well as LT production, as did DEC.
      We conclude that 1) the extended pulmonary hypertension induced by PAF was caused
      mainly by prolonged activation of 5-lipoxygenase with LTC4 production, 2) the
      relative overall lung clearance of LTB4, LTD4, and LTE4 was slower than that of
      LTC4, and 3) LTB4, LTD4, and LTE4 had no appreciable pressor effect.

PMID- 1400063
TI  - ACE inhibition facilitates sodium and water excretion during PEEP in conscious
      volume-expanded dogs.
AB  - Increased activity of the renin-angiotensin system may be involved in sodium and
      water retention during controlled mechanical ventilation (CMV) with positive end
      expiratory pressure (PEEP). We therefore evaluated renal, hemodynamic, and
      hormonal effects of an acute angiotensin-converting enzyme inhibition (ACEI)
      during PEEP and extracellular volume expansion in five trained chronically
      tracheotomized dogs. Three protocols were performed: control, 4 h spontaneous
      breathing with continuous positive mean airway pressure (Paw) of 4 cmH2O (CPAP
      4); CMV 20, CPAP for 1st h, CMV with 20 cmH2O Paw for 2 h (2nd and 3rd h), and 1
      h of CPAP (4th h); and CMV20-ACEI, ACEI (Ramipril, 2 mg/kg body wt) followed by
      the same protocol as in CMV 20. During control, sodium excretion (UNaV) and urine
      volume (V) increased continuously to 56.2 +/- 2.7 (SE) mumol.min-1.kg body wt-1
      and 482 +/- 23 microliters.min-1.kg body wt-1, respectively. UNaV and V increased
      less during PEEP in CMV 20 and CMV 20-ACEI. However, significantly more sodium
      and water were retained in CMV 20 than in CMV 20-ACEI (2.3 +/- 0.3 vs. 1.0 +/-
      0.3 mmol/kg body wt, and 20 +/- 3 vs. 11 +/- 2 ml/kg body wt) because of a
      decrease of glomerular filtration rate and fractional UNaV in CMV 20. Heart rate
      did not change in control, CMV 20, or CMV 20-ACEI. Mean arterial pressure
      increased during control by 13 mmHg, did not change during CMV 20, and was
      decreased by 7 mmHg in CMV 20-ACEI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400064
TI  - Effect of downhill running on motoneuron pool excitability.
AB  - The purpose of this study was to compare alterations in motoneuron pool
      excitability after eccentric-biased (ECC-B) downhill running exercise with non
      biased (NO-B) level running exercise. Six male subjects (25-34 yr) participated
      in the study, which included ECC-B exercise (-10% grade) and NO-B exercise (0%
      grade) at 50% of maximal O2 uptake for 20 min. The control trial consisted of 20
      min of quiet rest with all subjects participating in all conditions (repeated
      measures). Motoneuron pool excitability was measured by the Hoffman reflex (H
      wave), which was expressed as a ratio (H/M ratio) of the maximal electrically
      stimulated muscle action potential (M-wave). NO-B exercise resulted in a 9.3 +/-
      2.7% (SE) reduction in the H/M ratio. ECC-B exercise resulted in a 24.6 +/- 5.7%
      reduction in the ratio (P less than 0.05 for both). The two exercise treatment
      conditions were also significantly different from one another (P less than 0.05).
      Twenty-four-hour postexercise H/M ratios were similar to baseline (P greater than
      0.05). Postexercise subjective muscle soreness assessment (DOMS) produced
      significant increases in DOMS of 36 and 166% immediately and 24 h after exercise,
      respectively, for the ECC-B trial only (P less than 0.001). The data show that
      ECC-B exercise results in greater postexercise H/M ratio reductions than NO-B
      exercise and that H/M ratio changes post-ECC-B exercise are not solely associated
      with DOMS.

PMID- 1400065
TI  - Effect of acute nutritional deprivation on diaphragm structure and function in
      adolescent rats.
AB  - The influence of 90 h of acute nutritional deprivation (ND; water ad libitum
      only) on in vitro contractile and fatigue properties, muscle fiber type
      proportions, and cross-sectional areas (CSA) of the adolescent rat diaphragm was
      determined. Diaphragm muscle properties in the ND rats were compared with those
      in control rats (CTL; food and water ad libitum). Acute ND resulted in a 32%
      reduction in body mass, whereas the body mass of CTL rats increased by 29%. Acute
      ND resulted in a significant reduction in the mass of the diaphragm (costal, 36%;
      crural, 43%), soleus (36%), and medial gastrocnemius (45%) muscles. Isometric
      twitch characteristics of the diaphragm muscle (contraction and half-relaxation
      times) were prolonged in the ND animals. Peak twitch and maximum tetanic forces
      were unaffected by ND. Fatigue resistance of the diaphragm muscle was improved in
      ND animals. Diaphragm muscle fiber type proportions were similar in ND and CTL
      groups. The CSA of type I and II diaphragm muscle fibers were reduced by 22 and
      40%, respectively, in ND animals compared with CTL. We conclude that, whereas an
      identical protocol of acute ND had no significant effects on diaphragm muscle
      structure and function in adult rats, adolescent animals exhibit significantly
      less nutritional reserve. These differences may be due to curtailment of the
      rapid anabolic rate in growing animals.

PMID- 1400066
TI  - Parasternal and external intercostal responses to various respiratory maneuvers.
AB  - Recent studies suggest that the external intercostal (EI) muscles of the upper
      rib cage, like the parasternals (PA), play an important ventilatory role, even
      during eupneic breathing. The purpose of the present study was to further assess
      the ventilatory role of the EI muscles by determining their response to various
      static and dynamic respiratory maneuvers and comparing them with the better
      studied PA muscles. Applied interventions included 1) passive inflation and
      deflation, 2) abdominal compression, 3) progressive hypercapnia, and 4) response
      to bilateral cervical phrenicotomy. Studies were performed in 11 mongrel dogs.
      Electromyographic (EMG) activities were monitored via bipolar stainless steel
      electrodes. Muscle length (percentage of resting length) was monitored with
      piezoelectric crystals. With passive rib cage inflation produced either with a
      volume syringe or abdominal compression, each muscle shortened; with passive
      deflation, each muscle lengthened. During eupneic breathing, each muscle was
      electrically active and shortened to a similar degree. In response to progressive
      hypercapnia, peak EMG of each intercostal muscle increased linearly and to a
      similar extent. Inspiratory shortening also increased progressively with
      increasing PCO2, but in a curvilinear fashion with no significant differences in
      response among intercostal muscles. In response to phrenicotomy, the EMG and
      degree of inspiratory shortening of each intercostal muscle increased
      significantly. Again, the response among intercostal muscles was not
      significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400067
TI  - A simple distensible vessel model for interpreting pulmonary vascular pressure
      flow curves.
AB  - A simple distensible vessel model was developed for the purpose of interpreting
      the vascular pressure-flow curve in the zone 3 lung. The model-governing equation
      has two parameters: R0, representing the hemodynamic resistance of the
      undistended pulmonary vascular bed, and alpha, representing the distensibility of
      the resistance vessels. To evaluate the model, the governing equation was used in
      a nonlinear regression analysis of the pressure-flow data from isolated dog lung
      lobes. The dependency of the estimates of the model parameters in response to
      changes in perfusate viscosity (hematocrit) was determined. The distensible
      vessel model provided reasonable fits to the data, and, as predicted, R0, but not
      alpha, was hematocrit dependent. On the other hand, the traditional linear ohmic
      Starling resistor model fit to the same pressure-flow data generally provided
      fits approaching those of the distensibility model only if the pressure intercept
      (the mean "critical closing pressure") was allowed to increase with hematocrit.
      Because the ohmic-Starling resistor concept does not predict a hematocrit
      dependence of the critical closing pressure, this latter observation is evidence
      that the distensible vessel model offers an alternative conceptualization of the
      pulmonary circulation worthy of additional study with respect to the
      interpretation of experimental pressure-flow data.

PMID- 1400068
TI  - Respiratory phasic effects of inspiratory loading on left ventricular
      hemodynamics in vagotomized dogs.
AB  - Exaggerated inspiratory swings in intrathoracic pressure have been postulated to
      increase left ventricular (LV) afterload. These predictions are based on
      measurements of LV afterload by use of esophageal or lateral pleural pressure.
      Using direct measurements of pericardial pressure, we reexamined respiratory
      changes in LV afterload. In 11 anesthetized vagotomized dogs, we measured
      arterial pressure, LV end-systolic (ES) and end-diastolic transmural (TM)
      pressures, stroke volume (SV), diastolic left anterior descending blood flow (CBF
      D), and coronary resistance. Dogs were studied before and while breathing against
      an inspiratory threshold load of -20 to -25 cmH2O compared with end expiration.
      Relative to end expiration, SV and LVES TM pressures decreased during inspiration
      and increased during early expiration, effects exaggerated during inspiratory
      loading. In all cases, LV afterload (LVES TM pressure) changed in parallel with
      SV. LV end-diastolic TM pressure did not change. CBF-D paralleled arterial
      pressure, and there were no changes in coronary resistance. In two dogs, regional
      LVES segment length paralleled calculated changes in LVES TM pressure. We
      conclude that 1) LV afterload decreases during early inspiration and increases
      during early expiration, changes secondary to those in SV; 2) changes in CBF-D
      are secondary to changes in perfusion pressure during the respiratory cycle; and
      3) the use of esophageal or lateral pleural pressure to estimate LV surface
      pressure overestimates changes in LV TM pressures during respiration.

PMID- 1400069
TI  - Biology of inherited coagulopathies: von Willebrand factor.
AB  - von Willebrand disease is a common inherited bleeding disorder due to qualitative
      or quantitative abnormalities in von Willebrand factor. This article reviews the
      progress that has been made over the past few years in defining the molecular
      basis of von Willebrand disease. It should soon be possible to precisely diagnose
      and classify many cases of von Willebrand disease using modern genetic
      techniques.

PMID- 1400070
TI  - Hemophilia A.
AB  - Over the past few years considerable progress has been made in elucidating the
      molecular genetics of hemophilia A, in carrier detection and prenatal diagnosis,
      and in the production of safer clotting factor concentrates. Recombinant FVIII,
      shown to be safe and effective in ongoing prelicensure clinical trials that began
      in the spring of 1987, should soon be licensed and commercially available. There
      is now considerable interest in beginning prophylactic therapy regimens at 1 or 2
      years of age, in an attempt to prevent chronic joint disease and other
      complications of serious bleeding episodes. The possibility of gene insertion
      therapy for persons with hemophilia now seems to be a realistic one--perhaps
      achievable in the 1990s. Although many problems remain--major problems resulting
      from HIV, HCV, and HBV infections; how to deal with existing musculoskeletal
      problems; how to pay for the higher-priced new technologies; high titer
      inhibitors; just to name a few--the many recent scientific advances and their
      clinical applications make this an exciting time. This is truly, as indicated in
      the title of the proceedings of the XIX Congress of the World Federation of
      Hemophilia, a new decade of hopes and challenges.

PMID- 1400071
TI  - Management of hemophilia patients with inhibitors.
AB  - rFVIIa seems to offer an alternative in the treatment of hemophiliacs as well as
      nonhemophiliacs with antibodies against FVIII/FIX. The treatment can be given
      regardless of the inhibitor titer in those patients and is also hemostatically
      active in hemophilia B patients. It is easy to administer but seems to need a
      repeated dosing at 2- to 3-hour intervals, at least initially in severe
      bleedings. A dose of 70 to 100 micrograms/kg body weight seems to induce
      hemostasis. Depending on the severity of the bleeding, the dose intervals may
      then be prolonged to 3 hours for 1 to 2 days or until clinical improvement is
      observed. Thereafter, the dosage interval can be increased to 4 hours if
      continued therapy is indicated.

PMID- 1400072
TI  - The safety of blood components and derivatives.
AB  - An overview of the steps taken to ensure the safety of blood components and
      derivatives is provided. A brief discussion of hereditary bleeding disorders
      (hemophilia A, B, and von Willebrand's disease) is included, and the safety of
      derivatives available for their treatment is discussed, as well as the method of
      production and the level of safety of derivatives such as factor VIII and factor
      IX concentrates.

PMID- 1400074
TI  - Considerations for using lower doses of warfarin.
AB  - Warfarin is a very effective anticoagulant when used in the standard dose;
      however, the definition of standard dose has become ambiguous as the importance
      of the thromboplastin used in the measure of the prothrombin times has been
      demonstrated. Full or "standard" anticoagulation with warfarin imposes a
      hemorrhagic risk that can be avoided using lower doses. The premise has now been
      established that less than standard doses are efficacious. What is yet to be
      determined, however, is how low the dose of warfarin may be while maintaining
      efficacy and in which clinical settings. These conclusions must be established
      cautiously in clinical settings before being advocated generally. More complete
      discussions of this topic as well as safer means of using warfarin in general are
      available.

PMID- 1400073
TI  - Treatment of von Willebrand's disease.
AB  - Recent unraveling of the molecular and cellular biology of vWF and clearer
      knowledge of the pathophysiology of vWD have dramatically advanced our
      understanding of this group of disorders. Nonetheless, safe, effective,
      therapeutic management remains a formidable challenge for the clinician caring
      for these patients.

PMID- 1400075
TI  - Antithrombin III concentrates.
AB  - The general characteristics of antithrombin III (AT III) concentrates available
      in the United States are described in this article. The effectiveness of AT III
      concentrates in the prevention and treatment of thrombotic episodes in patients
      with hereditary AT III deficiency are summarized, and the use of this product in
      various conditions with acquired AT III deficiency are reported.

PMID- 1400076
TI  - Leeches to hirulogs and other thrombin-directed antithrombotics.
AB  - Leeches have been used for various medicinal purposes since before written
      history. Bloodletting and leeching declined with the advent of modern medicine.
      Nevertheless, the European medicinal leech has made a comeback in reattachment
      and plastic surgery. The antithrombotic substance of this leech is the small
      protein, hirudin, which has recently been cloned and advanced as an
      antithrombotic. From speculating how hirudin interacted with thrombin and before
      knowledge of the crystallographic structures of hirudin-thrombin complexes, the
      bridge-binding double-ligand concept was born and led to the highly specific
      thrombin inhibitors of the hirulog class. Like heparin, hirulogs and recombinant
      hirudins are not orally active but should fill needs where heparin and its
      derivatives have shortcomings. On the other hand, they most likely will be
      supplanted by small-molecule thrombin inhibitors when sufficiently specific and
      nontoxic ones are found. Other approaches to antithrombotic therapy include
      modulating cellular functions of thrombin. Because thrombin has central
      bioregulatory functions in thrombosis and hemostasis, as well as wound healing,
      it is an attractive target for antithrombotic intervention.

PMID- 1400077
TI  - Noninvasive carotid duplex ultrasound imaging for the evaluation and management
      of carotid atherosclerotic disease.
AB  - Renewed interest in surgical management of atherosclerotic disease of the carotid
      bifurcation underscores the necessity for accurate and efficacious means for
      diagnostic evaluation of patients with suspected carotid disease. Noninvasive
      testing by carotid duplex ultrasound, which combines high-resolution B-mode
      imaging with pulsed Doppler spectral analysis, is the method of choice.
      Noninvasive testing permits identification of potentially significant carotid
      stenosis, occlusion, or unstable plaque morphology with virtually no significant
      morbidity from the testing itself. Symptomatic patients, or patients with
      asymptomatic carotid bruits, can be evaluated serially to determine disease
      progression or response to medical management. In patients who are surgical
      candidates, substitution of noninvasive duplex ultrasound evaluation for carotid
      arteriography is controversial. Noninvasive testing is highly technique-dependent
      and probably requires at least 1 year of experience for acquisition of a
      sufficient "learning curve" for diagnostic reliability. This applies not only to
      the technical performance of the test but to interpretation of results. Proper
      training of technicians and quality assurance in individual vascular laboratories
      are crucial elements with respect to accuracy and reliability of results obtained
      in noninvasive testing.

PMID- 1400078
TI  - Approach to the patient with venous thromboembolism. Treatment with thrombolytic
      agents.
AB  - This article reviews the different thrombolytic agents currently available and
      the different mechanisms by which they activate the body's fibrinolytic system.
      The discussion is confined to the approach to the patient with venous
      thromboembolism using the different thrombolytic agents. Data are presented
      supporting the use of thrombolytic therapy and its long-term benefits, especially
      in patients with pulmonary embolism. A substantial portion of this article is
      devoted to practical considerations involved in the administration of
      thrombolytic therapy.

PMID- 1400079
TI  - Current concepts in coronary thrombolysis.
AB  - It has become increasingly apparent that the success of coronary thrombolysis
      depends on a dynamic balance between fibrinolytic and procoagulant activity. The
      differential properties of specific plasminogen activators determine the rate at
      which clot lysis is induced, the extent to which procoagulant activity and
      platelet activation are increased, and the extent to which recurrent thrombosis
      is inhibited. Current conjunctive regimens (aspirin and heparin) appear to
      attenuate but not preclude recurrent thrombosis in patients treated with coronary
      thrombolysis. The recent development of a variety of new anticoagulants with
      different mechanisms of action may result in even more effective treatment
      strategies. Whether these newer agents will result in improved survival in
      patients treated with coronary thrombolysis without compromising safety will need
      to be established by clinical trials.

PMID- 1400080
TI  - Fibrinogen anomalies and disease. A clinical update.
AB  - The precipitous increase in the number of structurally defined fibrinogen defects
      in recent years has resulted from application of high performance liquid
      chromatography in combination with peptide mapping and sequencing procedures.
      More recently, application of DNA sequence of polymerase chain reaction products
      has accelerated the pace of identification of mutations. Highly frequent defects
      are Arg substitutions, accounting for eight mutation sites substituted by Cys or
      His and less frequently by Ser. Amino acid substitutions at different positions
      on all three chains have pointed to possible structures with polymerization
      related functions. Also, substitutions yielding consensus sequences resulted in
      extra glycosylations of the appropriate Asn in four different mutation sites; the
      impaired polymerization was reported associated with undue bleeding in two of
      these. Among informative defects have been those of homozygous probands with A
      alpha 16Arg----His and A alpha 16Arg----Cys in that failure of release of peptide
      A (but not of B), as shown with A alpha 16Arg----Cys, resulted in markedly
      delayed polymerization of such fibrin monomers, in general agreement with
      conclusions reached in studies of normal fibrin. This dysfunction, as well as the
      slow rate of release of A shown with A alpha 16Arg----His, was associated with
      clinically significant hemorrhagic diathesis (in the homozygous probands),
      consistent with the known physiologic importance of peptide A cleavage in normal
      hemostasis. Also, defects on the A alpha 17-19 sequence resulting in impaired
      polymerization are consistent with the known role of this segment in
      polymerization. Of similar interest have been defects within a B beta chain span
      encoded its exon 2. Two defects resulting in impaired polymerization and thrombin
      binding were associated with clinical thrombosis commencing in early life, and
      this lends strong support to other evidence suggesting a role in polymerization
      and in noncatalytic thrombin binding by this B beta chain segment. Thrombosis
      associated with A alpha 554Arg----Cys in a heterozygous proband with impaired tPA
      interaction is unique and may shed light on this poorly understood but important
      interaction among fibrin, plasminogen, and tPA. A group of different defects
      within the gamma 275-375 sequence have pointed to a polymerization role,
      evidenced by delayed gelation and impaired binding of mutant D to normal fibrin
      E. An unusual example is a 15 residue insertion between gamma 350 and 351
      resulting in impaired polymerization, gamma chain crosslinking, and platelet
      aggregation support and is associated with hemorrhagic diathesis and poor
      healing.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1400082
TI  - Approach to the bleeding patient.
AB  - A broad, open, inquisitive, and semiskeptical mind must be used when approaching
      the bleeding patient. As in most endeavors in medicine, the history and physical
      examination provide an important baseline. Key laboratory tests must be quickly
      ordered and interpreted. Using this data base, one can quickly determine whether
      the hemorrhagic disorder is congenital or acquired, severe or mild, and
      progressive or stable. Hemostasis may fail owing to deficiencies of platelets,
      the plasma coagulation protein system, or endothelial disturbances. A precise
      diagnosis and appreciation of the tempo of the disorder will guide specific
      therapy.

PMID- 1400081
TI  - Hemostatic aspects of envenomation by North American snakes.
AB  - 1. North American poisonous snakes have a wide spectrum of complex venoms. 2.
      Venom, especially that of the rattlesnakes, may cause a variety of hemostatic
      abnormalities by directly, yet only partially, cleaving fibrinogen, activating
      the fibrinolytic system, or activating and clearing platelets through the action
      of proteolytic enzymes. 3. Because these venoms do not result in the generation
      of thrombin, the syndrome is distinct from true DIC. Bleeding or thrombosis is
      rare. 4. As thrombin generation remains intact, hemostasis is largely preserved
      despite dramatic changes in hemostatic tests. 5. Therapy with heparin, blood, or
      blood products is rarely indicated. 6. Therapy with antivenin in selected cases
      is logical and efficacious.

PMID- 1400083
TI  - Biology of factor IX.
AB  - Hemophilia B, one of two common hereditary bleeding disorders, is caused by a
      deficiency of factor IX in the circulation. Molecular mechanisms of hemophilia B
      are highly heterogeneous including gene deletions, insertions, complex
      rearrangements, and a large number of point mutations. Currently, hemophilia B is
      treated by plasma protein replacement therapy. This therapy is effective but
      exposes patients to possible side effects and complications such as infection of
      blood-borne pathogens including hepatitis viruses and HIV-1. Intensive efforts to
      develop alternative, safer therapies for hemophilia B, including somatic gene
      therapy, are now under way.

PMID- 1400084
TI  - Acute hemorrhagic myocarditis in systemic lupus erythematosus.
AB  - We report a 46-year-old patient with longstanding systemic lupus erythematosus
      (SLE) who developed rapidly progressive heart failure and died. At postmortem,
      there was a unique picture of hemorrhage and mild inflammation present in the
      myocardium causing the heart failure. As far as we are aware, this picture has
      not been described before in SLE and is similar to that seen in the cardiac
      allograft hyperacute rejection.

PMID- 1400085
TI  - Ejecting volume, filling volume and stroke volume gains: new indexes of
      inotropism and lusitropism.
AB  - We propose new indexes to evaluate the effects of ventricular inotropism and
      lusitropism on stroke volume. The end-systolic pressure-volume relationship
      (ESPVR) or its slope (Emax) has been employed to assess ventricular inotropism.
      The end-diastolic pressure-volume relationship (EDPVR) or compliance has been
      used to express ventricular diastolic properties or lusitropism. However, their
      net effect on stroke volume under a given set of preload and afterload pressures
      has not quantitatively been evaluated. Ejecting volume gain (Ge) was proposed to
      quantify the inotropic effect on stroke volume by the change in end-systolic
      volume between the two ESPVR curves obtained before and during an inotropic
      intervention at a specified ejecting pressure. Ge is a function of afterload
      pressure. Filling volume gain (Gf) was proposed to quantify the lusitropic effect
      on stroke volume by the change in end-diastolic volume between the two EDPVR
      curves before and during a lusitropic intervention at a specified filling
      pressure. Gf is a function of preload pressure. The net effect of these inotropic
      and lusitropic effects on stroke volume at these specified preload and afterload
      pressures can be expressed by the sum of Ge and Gf. We call this sum stroke
      volume gain (Gsv). Gsv is a function of preload and afterload pressures. Using
      representative examples, we demonstrate that these new indexes are conceptually
      useful to quantitatively understand changes in the pumping ability of the heart
      under simultaneous inotropic and lusitropic effects as a function of ejecting and
      filling pressures.

PMID- 1400086
TI  - Unroofed coronary sinus syndrome: diagnostic consideration by contrast
      echocardiography and usefulness of transesophageal echocardiography and magnetic
      resonance imaging.

PMID- 1400087
TI  - Usefulness of ultrasonography and Doppler color flow imaging in the diagnosis of
      internal jugular phlebectasia.
AB  - A 20-year-old woman presented to our hospital for investigation of a left neck
      mass. Ultrasonographic examination of the jugular mass demonstrated an echo-free
      space, the caliber of which markedly increased when the patient shifted from the
      sitting to the recumbent position or performed a Valsalva maneuver. On color
      Doppler flow imaging, a slow flow signal flowing in the direction opposite to
      that of the common carotid artery was found within this space. Ultrasonography
      and color Doppler flow imaging thus proved to be useful for correctly diagnosing
      internal jugular phlebectasia.

PMID- 1400088
TI  - Color Doppler and transesophageal echocardiography of vascular sling.
AB  - Three patients with vascular sling were studied by two-dimensional and color
      Doppler echocardiography and angiocardiography. One case was associated with
      atrial septal defect and another with tetralogy of Fallot and patent ductus
      arteriosus. The third case had no associated intracardiac anomalies. Color
      Doppler flow mapping was performed in all three patients, and transesophageal
      echocardiography was studied in two patients. Color Doppler echocardiography
      showed the characteristic features of this congenital anomaly in all three
      patients, especially in detecting the site of anomalous origin of the left
      pulmonary artery. A small patent ductus arteriosus was misinterpreted as the
      normal left pulmonary artery in one patient. Small pulmonary arteries in the
      patient with tetralogy of Fallot made the diagnosis difficult. Using
      transesophageal echocardiography, we clearly identified the trachea, esophagus,
      and abnormal left pulmonary artery.

PMID- 1400089
TI  - Addressing the state's need for primary care.

PMID- 1400090
TI  - Knowledge of chemical abuse and AIDS among gifted junior high school students in
      Little Rock.
AB  - A 12-question test was composed and administered to the seventh, eighth, and
      ninth grade Gifted-Talented (GT) Science Classes. A clustered stratified random
      sample of 66 students was selected out of the 194 students. The mean score was
      70% for the eighth grade, 68% for the seventh grade, and 62% for the ninth grade.
      Knowledge among the students was especially deficient regarding the risk of legal
      drugs of abuse, i.e., cigarettes and alcohol.

PMID- 1400091
TI  - On the other side.

PMID- 1400092
TI  - Tobacco's new adversary.

PMID- 1400093
TI  - So you want to live to be 100?

PMID- 1400094
TI  - Analysis of a pediatric death suit: negligence occurred but causation and the
      jury contribute to defense verdict.

PMID- 1400095
TI  - Arkansas HIV/AIDS report. 1983-1992.

PMID- 1400096
TI  - U.S. health care primary care perspective.

PMID- 1400097
TI  - Update of the worldwide FDA study of the 3M diffractive multifocal intraocular
      lens.
AB  - The multifocal diffractive intraocular lens (IOL) represents a significant
      technological advance. Results of 671 patients with a year follow-up from a
      worldwide study are presented. Through this FDA study, it appears that many
      patients can enjoy uncompromising distance vision as well as unaided near vision.
      With careful surgical control of astigmatism and competent calculation of IOL
      power, it may be possible to reduce the post-cataract patients' dependency on
      glasses.

PMID- 1400099
TI  - Physicians and their medical assistants investing in a valuable resource.

PMID- 1400098
TI  - Torsion of the gallbladder. A review of four cases.
AB  - Four cases of torsion of the gallbladder have been gathered from this area. Three
      were admitted to our local hospitals and the fourth case occurred in the
      Veteran's Hospital in Fayetteville. The average age of these four cases was 85,
      and all patients were very thin. Three patients were female and one was male. One
      patient died following surgery. This patient had sought help rather late, and
      died of cardiopulmonary complications. This entity is rare, and only scattered
      cases are found in the literature. Biliary calculi are found in approximately 50%
      of the cases. The exact etiology of the torsion is unknown. A redundant mesentery
      is always present, and kyphosis is frequent. Our patients were all thin. Botha
      has postulated that vigorous peristalsis in the neighboring viscera or sudden
      body movement may be responsible. The diagnosis is rarely made preoperatively,
      but if surgery is not done, death will probably ensue. Later reports have
      indicated that sonography and abdominal CT scanning might prove helpful in
      establishing a diagnosis.

PMID- 1400100
TI  - I know a little bit about a lot of things.

PMID- 1400101
TI  - Spontaneous internal carotid artery dissection.

PMID- 1400102
TI  - Questions about facilitated communication and autism.

PMID- 1400104
TI  - Remediating the thinking of pupils with autism: principles into practice.
AB  - We take previously developed principles of a problem-solving approach to teaching
      pupils with (Jordan & Powell, 1990a, 1990b, 1991), and analyze their application
      within the normal teaching routine of a specialist school for such pupils. We
      note the kinds of pedagogical judgment made, and the structures needed by
      individual pupils to enable them to function as problem solvers. We identify
      reflection as a key factor in enhancing the potential of pupils as learners and
      discuss ways of increasing pupils' awareness of their own ways of handling
      learning situations. The study is set against the background of issues concerned
      with possibilities of developing a 'theory of mind' in pupils with autism.

PMID- 1400103
TI  - Autism and tuberous sclerosis.
AB  - Autism is a behavior disorder with genetic influences indicated from twin and
      family studies and from the co-occurrence of autism with known genetic disorders.
      Tuberous sclerosis complex (TSC) is a known genetic disorder with behavioral
      manifestations including autism. A literature review of these two disorders
      substantiates a significant association of autism and TSC with 17-58% of TSC
      subjects manifesting autism and 0.4-3% of autistic subjects having TSC. In
      initial data collected on 13 TSC probands and 14 autistic probands in our family
      study of autism and TSC, we identified 7 TSC subjects with autism. The seven TSC
      autistic probands are similar to non-TSC autistic probands on the Social and
      Communication domains of the Autism Diagnostic Inventory (ADI) (Le Couteur et
      al., 1989), but show fewer Repetitive Rituals. There are more male TSC probands
      with autism than female, despite an equal sex ratio among TSC probands. The TSC
      probands with autism have significantly more seizures and mental retardation than
      those without autism; however, the extent and etiology of associations require
      further study. Our preliminary findings suggest that a fruitful approach for
      delineating genetic influences in autism may come from further investigation of
      possible mechanisms underlying the association of autism and TSC.

PMID- 1400106
TI  - Does oxytocin deficiency mediate social deficits in autism?

PMID- 1400105
TI  - Urinary cortisol circadian rhythm in a group of high-functioning children with
      autism.
AB  - Previous research has suggested that there may be dysfunction in the control of
      the hypothalamic-pituitary-adrenal axis in autistic children. Both an abnormal
      cortisol circadian rhythm and failure to suppress cortisol secretion in response
      to dexamethasone have been reported. This study investigated the basal urinary
      cortisol circadian rhythm in a group of high-functioning children with autism and
      matched controls. No evidence was found for abnormal temporal placement of the
      circadian rhythm in the autistic group. There was a tendency towards cortisol
      hypersecretion during the day, predominantly in those autistic children who were
      integrated into the normal school system. While the temporal parameters of the
      cortisol circadian rhythm in these children with autism were probably normal, the
      tendency towards cortisol hypersecretion may indicate an environmental stress
      response in this group.

PMID- 1400107
TI  - Correction to previous evaluation of facilitated communication.

PMID- 1400108
TI  - The prevalence of Rett syndrome and infantile autism in Chikugo District, the
      southwestern area of Fukuoka prefecture, Japan.

PMID- 1400109
TI  - Prevalence and correlates of the premenstrual syndrome in adolescence.
AB  - In a longitudinal study of their health and development, 384 15-year-old females
      reported their experience of symptoms indicative of premenstrual syndrome (PMS).
      The prevalence of these symptoms is reported and a group of adolescents is
      identified with the syndrome (14%). PMS was associated with current self-reported
      anxiety, inattention, and poor health. Preadolescent self-report and maternal
      ratings of physical and mental health did not significantly predict adolescent
      PMS. The results suggest that the experience of PMS in adolescence may be
      mediated by perceived health status; the roles of mental health and maternal
      influence in the development of adolescent PMS may be minimal.

PMID- 1400110
TI  - Sex differences in the interaction between temperament and parenting.
AB  - Temperament and parent-child relationships were measured in a random sample of
      776 children followed over a 10-year period. The goal was to determine whether
      temperament evolves differently for boys versus for girls, and if so, whether
      parenting influences gender-specific development. Gender-specific parenting
      effects on the evolution of difficult temperament were found: low father-daughter
      closeness, and high mother-son punishment and control led to an increase in
      difficult temperament, whereas comparable father-son and mother-daughter effects
      were not present. A possible explanation for these findings is proposed. The
      contribution of these findings to understanding biology-environment interactions
      in causing sex differences in development is discussed.

PMID- 1400111
TI  - Psychiatric comorbidity in treatment-seeking anorexics and bulimics.
AB  - Current and lifetime psychiatric diagnoses were compared in 229 female patients
      seeking treatment for current episodes of anorexia nervosa (N = 41), bulimia
      nervosa (N = 98) and mixed anorexia nervosa and Schizophrenia-Lifetime Version,
      which was modified to include a section for DSM-III-R eating disorders, the
      Longitudinal Interval Follow-up Evaluation, and the Structured Interview for DSM
      III Personality Disorders. Seventy-three percent of the anorexia nervosa
      subjects, 60% of the bulimia nervosa subjects, and 82% of the mixed anorexia
      nervosa and bulimia nervosa subjects had a current comorbid Axis I diagnosis.
      Major depression was the most commonly diagnosed comorbid disorder. Low rates of
      alcohol and substances abuse disorder were diagnosed, and personality disorder
      occurred in a minority of the sample. The subjects with mixed disorder manifested
      a higher lifetime prevalence of kleptomania than either the anorexics or the
      bulimics. High levels of comorbidity were noted across the eating disorder
      samples. Mixed disorder subjects manifested the most comorbid psychopathology and
      especially warrant further study.

PMID- 1400112
TI  - Anorexia nervosa in 51 Swedish adolescents: premorbid problems and comorbidity.
AB  - Fifty-one teenage cases with anorexia nervosa (AN) were compared with 51 age-,
      sex-, and school-matched cases with respect to premorbid developmental, physical,
      and psychiatric problems and comorbidity at the time of examination. Almost half
      of the AN group consisted of the total population of AN cases in one birth
      cohort. There were more premorbid personality problems in the AN group. Obsessive
      compulsive problems were very common in this group, as was undue concern about
      physical appearance. Depressive symptoms during the course of the eating disorder
      were almost universal in the AN group, but it did not appear that such symptoms
      had preceded the eating disorder. It seems that there may be a number of
      subgroups with AN and that the majority of these can be better understood in the
      light of factors intrinsic to the patients themselves rather than in the context
      of deviant family interaction.

PMID- 1400113
TI  - Personality dimensions in eating disorders and their relevance for subtyping.
AB  - Personality dimensions and psychopathological symptoms were assessed in 50 female
      patients hospitalized for the treatment of anorexia nervosa or bulimia nervosa
      and in 19 healthy female controls of similar age. Restricting anorexia nervosa
      patients, who had lost weight by consistently reducing their food intake,
      reported significantly greater self-control, inhibition of emotionality, and
      conscientiousness than controls or bulimia nervosa patients, before and after the
      data were corrected for depressive and eating pathology. Both nonbulimic and
      bulimic anorexia nervosa patients expressed stronger than normal conformance to
      moral and family values. On the impulsivity dimension, bulimia nervosa patients
      scored in the high normal range, whereas bulimic anorexia nervosa patients rated
      in the low normal range. The results suggest that a personality disposition
      toward overcontrol and reserve might constitute a risk factor for the restricting
      type of anorexia nervosa through fostering restrictive behavior toward food and
      avoidance of personal relationships.

PMID- 1400114
TI  - Psychopathology in anorexia nervosa and depression.
AB  - It has been hypothesized that anorexia nervosa is characterized by
      ineffectiveness, interpersonal distrust, and lack of interoceptive awareness. The
      Eating Disorder Inventory differentiates patients with anorexia nervosa from
      weight-preoccupied women on the basis of these subscales. To test further the
      specificity of these characteristics to anorexia nervosa, the Eating Disorder
      Inventory scores of 20 adolescent girls diagnosed with anorexia nervosa were
      compared with those of 21 girls with major depression and 21 girls with both
      anorexia nervosa and depression. Analyses of variance and discriminant function
      analysis revealed no significant differences in the scores of the three groups.
      By 2-year followup, subjects initially diagnosed with only anorexia nervosa
      showed less psychopathology than those with an additional diagnosis of
      depression. These findings raise further questions about the overlap between
      depression and anorexia nervosa and leave open the question of characteristic
      psychological features in anorexia nervosa.

PMID- 1400115
TI  - The intellectual functioning of eating disorder patients.
AB  - This study investigated the intellectual functioning of a large group of eating
      disorder patients to examine two previously reported findings: (1) this
      population exhibits above-average general intellectual skills; and (2) a specific
      pattern of strength in verbal abilities. Standard intellectual testing of 100
      consecutive inpatient females with eating disorder diagnoses was performed.
      Results indicate intellectual performance conforming to a normal distribution
      with no specific pattern of strengths or weaknesses.

PMID- 1400116
TI  - Cognitive-behavioral treatment of health-impairing food phobias in children.
AB  - Three cases reports describe assessment and treatment of three boys (ages 6 to 8
      years) hospitalized because of weight loss and malnutrition, caused by severe
      dietary restriction and/or refusal to eat solid food. Psychological, behavioral,
      and medical assessments indicated that the boys were of average intelligence,
      without other significant psychological or medical disorders. Their eating
      disturbances were conceptualized as phobic disorders maintained by family factors
      reinforcing the children's avoidant behaviors. Cognitive-behavioral treatment
      consisted of an individualized combination of contingency management, shaping,
      desensitization, relaxation training, education, and cognitive restructuring.
      Generalization and maintenance were promoted by training parents to implement
      treatment at home before discharge. Treatment positively affected overall caloric
      intake, weight gain, number of solid foods accepted, and incidence of emesis.

PMID- 1400117
TI  - Aggression in preschoolers: its relation to socialization.
AB  - The present article discusses developmental changes of aggression seen in
      preschool children and reports on an 18-month short-term prospective study of
      three preschool populations: a group referred for aggressive behavior problems, a
      normal control group, and a group of youngsters who had lived in violent homes,
      but showed no aggressive behaviors. Results indicate that the aggressive
      children, in comparison with the other two groups at age 4, showed a significant
      delay in their interpersonal awareness and perspective taking ability. However,
      although the aggressive children caught up with their peers in the course of the
      study period, there was no accompanying decrease in their aggressive behavior.
      The theoretical and clinical implications of these findings are discussed.

PMID- 1400118
TI  - Psychiatric diagnoses of maltreated children: preliminary findings.
AB  - The study sample consists of 96 children (61 maltreated, 35 controls) between 5
      and 10 years of age. The two groups of subjects were compared on diagnoses as
      determined by the administration of the Diagnostic Interview for Children and
      Adolescents, Revised 6th Version (DICA-6-R) as well as clinical DSM-III-R
      diagnoses. Children who had suffered maltreatment exhibited significantly greater
      incidences of attention deficit hyperactivity disorder, oppositional disorder and
      post-traumatic stress disorder diagnoses than did controls, on both child and
      parent DICA interviews. The children's interviews revealed that maltreated
      children present with a significant incidence of psychotic symptomatology as well
      as personality and adjustment disorders. Conversely, conduct and mood disorders
      emerged as significant factors in the parent interviews, with the maltreated
      group showing significantly greater incidence of these diagnoses.

PMID- 1400119
TI  - Maltreatment in psychiatrically hospitalized dually diagnosed adolescent
      substance abusers.
AB  - The medical charts of 150 consecutive admissions of dually diagnosed substance
      abusing adolescents admitted to a psychiatric hospital were examined to determine
      the extent and characteristics of maltreatment. Results indicated that 61% of the
      sample experienced or had a history that warranted suspicion of past and/or
      current maltreatment. Physical abuse was the most frequent form of maltreatment,
      followed by sexual abuse and neglect. Thirty-seven percent of patients
      experienced multiple forms of maltreatment. Maltreated patients had significantly
      more hospitalizations than their nonmaltreated counterparts on the same unit.
      Moreover, the age of maltreated patients was significantly lower than
      nonmaltreated patients, perhaps indicating an earlier age of onset of psychiatric
      illness and/or substance abuse. Analyses of parental substance abuse and
      psychiatric history among the maltreated and nonmaltreated groups revealed no
      significant findings. Results are discussed in terms of the following: (1)
      increased risk of subsequent substance abuse in maltreated children; (2) need for
      systematic assessment of child maltreatment in psychological or psychiatric
      evaluations; and (3) importance of treatment to deal with abuse or neglect as
      part of a comprehensive substance abuse intervention strategy.

PMID- 1400120
TI  - Sexually abused children at high risk for post-traumatic stress disorder.
AB  - Ninety-two sexually abused children were studied using structured interviews and
      standardized instruments to determine the frequency of post-traumatic stress
      disorder (PTSD) and associated symptoms. Of these sexually abused children, 43.9%
      met DSM-III-R PTSD criteria; 53.8% of children abused by fathers, 42.4% abused by
      trusted adults, and 10% of those abused by strangers met criteria as opposed to
      none of the children abused by an older child. No relationship was observed
      between the time lapsed since last abusive episode and the presence of PTSD. Many
      children not meeting full criteria exhibited partial PTSD symptoms. Only one
      standardized instrument (Child Behavior Checklist) detected group differences
      with PTSD children exhibiting more symptoms. This study replicates an earlier
      pilot study and underscores the need for further PTSD research.

PMID- 1400121
TI  - Child sexual abuse of Asians compared with other populations.
AB  - This retrospective chart review study of a child sexual abuse clinic compared a
      consecutive sample of substantiated sexual abuse cases of Asian victims with
      random samples of black, white, and Hispanic victims. The findings suggest that
      there are clinically relevant differences between Asians and the other three
      populations. Asian victims showed a distinct demographic profile, suffered less
      physically invasive forms of abuse, were more likely to express suicidality, less
      likely to display anger and sexual acting out, and had less supportive primary
      caretakers than non-Asians. Awareness of such ethnic differences will help
      clinicians better evaluate and treat minority victims.

PMID- 1400122
TI  - The failure of a school-based child sexual abuse prevention program.
AB  - Structured interviews were administered to 22 children, ranging in age from 6 to
      10 years old, who did not disclose long-term sexual abuse by an auxiliary school
      employee, despite having been exposed to a school-based child sexual abuse
      prevention program. The results are presented in the context of a review of
      existing literature on school-based child sexual abuse prevention programs.
      Results point to the ineffectiveness of brief, single presentation, prevention
      efforts not geared to specific developmental levels of the audience, the need to
      explore the impact of the variable of group versus individual victimization on
      disclosure, and the need for further study of sexually victimized children who
      received prevention programming with the addition of a control group sample.

PMID- 1400123
TI  - Child and family factors that ameliorate risk between 4 and 13 years of age.
AB  - Protective processes in at-risk children between 4 and 13 years of age were
      examined in a longitudinal study. A multiple risk index was used at 4 years to
      identify 50 high-risk children and 102 who were at low risk. Cognitive and social
      emotional status were measured at each time point. The following indicators of
      protective processes were related to positive change in cognitive and/or social
      emotional function in the high-risk children between 4 and 13 years: mother-child
      interaction; child perceived competence, locus of control, life events, and
      social support; and maternal parenting values, social support, depression, and
      expressed emotion. Many of these factors were also related to improvement in the
      low-risk children. Some variables showed an interaction effect, where impact was
      substantially higher in the high-risk group compared with the low-risk group. The
      utility of multiple risk constructs and process oriented approaches to protective
      factors are discussed.

PMID- 1400124
TI  - Interviews with children who experienced major life stress: family and child
      attributes that predict resilient outcomes.
AB  - Demographically comparable groups of children exposed to major life-stress, with
      stress resilient (SR) and stress affected (SA) outcomes at ages 10 to 12, were
      interviewed to assess perceptions of their caregiving environments, peer
      relationships, and themselves. SR children compared with SA children reported
      more: (1) positive relationships with primary caregivers, (2) stable family
      environments, (3) inductive and consistent family discipline practices, and (4)
      positive expectations for their futures. SR girls viewed their mothers as more
      nurturing than did SA girls. Perceptions of fathers, quality of peer
      relationships, and global self-concept did not differentiate the groups. A
      discriminant function analysis identified four variables that correctly
      classified 74% of the subjects as SR or SA. Findings support the view that
      caregiver-child relationships play a key role in moderating children's
      developmental outcomes under conditions of high stress.

PMID- 1400125
TI  - A risk profile predicting psychological distress in Vietnamese Amerasian youth.
AB  - The relationship between risk factors and psychological distress was examined in
      161 Vietnamese Amerasian youth. Background factors such as a history of missing
      school, frequent hospitalizations, and previous refugee camp experience
      distinguished those with higher levels of anxiety and depression. This study
      provides support for attempts to link specific risk factors with increased levels
      of psychological distress in immigrant populations. Confirmation of the
      predictive power of these risk factors awaits completion of a longitudinal study
      following the Ameriasians as they resettle in the United States.

PMID- 1400126
TI  - Outcome, prognosis, and risk in a longitudinal follow-up study.
AB  - This study reports the results of a 4-year follow-up of a community sample of
      children who were ages 4 to 12 in 1983 at the first wave of data collection.
      Results on outcomes revealed that conduct disorder showed the greatest stability
      especially from late childhood to early adolescence. In multivariate analyses,
      both family dysfunction and problems getting along with others significantly
      predicted the persistence of one or more psychiatric disorders 4 years later, and
      low income predicted one or more psychiatric disorders among children free of
      disorder 4 years earlier. The implications of the results for the child
      psychiatric field, especially prevention, are discussed.

PMID- 1400127
TI  - Six-year developmental course of internalizing and externalizing problem
      behaviors.
AB  - The 6-year developmental course of parent-reported problem behavior in an
      epidemiological sample of 936 children assessed with the Child Behavior Checklist
      at 2-year intervals was determined. Children who were scored in the deviant range
      of the total problem score at time 1 were nine times more likely to be scored
      deviant 6 years later than were children who were not deviant at time 1 (odds
      ratio 9.0). Of the deviant children at time 1, 33% were deviant at time 4. There
      was no difference in the persistence of externalizing versus internalizing
      problems. This underscores the notion that internalizing problems should not be
      disregarded. Although this study demonstrated moderate stability of problem
      behaviors across a 6-year interval, children's problem behaviors should not be
      regarded as static. Many children showed changes in their level of functioning
      across time. However, extreme changes were the exception rather than the rule.

PMID- 1400128
TI  - Three-year course of behavioral/emotional problems in a national sample of 4- to
      16-year-olds: I. Agreement among informants.
AB  - Quantitative and categorical indices of psychopathology are reported for a
      nationally representative longitudinal sample assessed via eight empirically
      derived cross-informants syndromes, internalizing, externalizing, and total
      problems. Results showed medium to large stabilities for parents' ratings during
      a 3-year interval on all comparable scales. Predictive correlations between time
      1 parents' ratings and time 2 teacher and self-ratings were weaker than parent-to
      parent correlations. Classification of children as deviant showed weaker
      predictive relations than did quantitative scores. Odds ratios showed that
      children classified as deviant by parents' time 1 ratings were much more likely
      to be deviant at time 2 on corresponding parent, teacher, and self-ratings than
      were children initially classified as nondeviant.

PMID- 1400129
TI  - Three-year course of behavioral/emotional problems in a national sample of 4- to
      16-year-olds: II. Predictors of syndromes.
AB  - This study examined relations between parents' ratings of children's
      behavioral/emotional problems, family variables, and stressful experiences as
      predictors of 3-year outcomes in a nationally representative sample of American
      children. Outcomes were measured by time 2 parent, teacher, and self ratings on
      eight empirically derived cross-informant syndromes. Path analyses indicated that
      parent ratings of each time 1 syndrome predicted parent ratings of the same time
      2 syndrome. Family variables and intervening stressful experiences predicted
      parent and self ratings, but not teacher ratings of syndromes. The number of
      family members receiving mental health services was the family variable that
      predicted the most time 2 syndromes. Parent reports of stress predicted parent
      ratings of time 2 syndromes, whereas child reports of stress predicted self
      ratings of time 2 syndromes.

PMID- 1400130
TI  - Children's mental health service needs and utilization patterns in an urban
      community: an epidemiological assessment.
AB  - To assess children's mental health service needs and utilization patterns for a
      state planning effort, a cross-sectional survey that sampled 822 children aged 6
      to 11 of a metropolitan center was conducted. When reports of parents and
      teachers were combined, 38.5% of children were screened to be at risk of
      psychiatric disturbance. Only 11% of children at risk received treatment in
      mental health settings, fewer than in schools (37%) or medical settings (13%).
      The findings illustrate the importance of interagency collaboration and the need
      to consider reports of parents and teachers and different dimensions of
      psychopathology in future planning and research.

PMID- 1400131
TI  - Communication deficits in childhood schizotypal personality disorder.
AB  - This study examined the similarities and differences in the communication
      deficits of 13 schizotypal and 12 schizophrenic children matched by age and IQ.
      Like schizophrenic children, schizotypal children underutilize some discourse
      devices necessary for coherent speech and overutilize others. Schizotypal
      children, however, appear to display a more restricted range of discourse
      deficits than schizophrenic children. In addition, their discourse deficits do
      not appear to be associated with clinical measures of loose associations. The
      clinical implications and the potential use of discourse measures to
      differentiate schizophrenic and schizotypal children are discussed.

PMID- 1400132
TI  - Schizophrenia with childhood onset: a phenomenological study of 38 cases.
AB  - Thirty-eight hospitalized children, ages 5.7 to 11.11 years, diagnosed with
      schizophrenic disorder by DSM-III criteria, are characterized regarding age, sex,
      race, socioeconomic status, pre- and perinatal complications,
      electroencephalogram, intelligence quotient, and family history of major
      psychiatric disorder. Clinical course, including age at onset of general and
      psychotic psychiatric symptoms and initial diagnosis of schizophrenic disorder,
      presence of DSM-III symptoms, hospital course, and response to antipsychotics are
      reviewed.

PMID- 1400133
TI  - Capgras syndrome in adolescence.
AB  - Capgras syndrome, the delusion of substitution, has rarely been reported in
      adolescents. The etiology is unknown, and intense controversy surrounds the
      debate over the relative importance of biological versus psychological factors.
      Presented here are two cases of Capgras syndrome in adolescents and a review of
      the relevant biological, neuropsychological, and psychodynamic literature. The
      authors suggest that the psychological processes underlying the Capgras delusion
      are mediated by neuroanatomical connections between various brain areas and
      hypothesize that the fundamental lesion in Capgras syndrome may be the patient's
      inability or failure to acknowledge the authenticity of a person they clearly
      recognize.

PMID- 1400134
TI  - Resolved: military family life is hazardous to the mental health of children.

PMID- 1400135
TI  - Debate: effects of watching violence.

PMID- 1400136
TI  - Debate: effects of watching violence.

PMID- 1400137
TI  - Debate: effects of watching violence.

PMID- 1400139
TI  - Imaging and eating disorders.

PMID- 1400138
TI  - Grand rounds: parental compliance.

PMID- 1400140
TI  - Anorectic family dynamics.

PMID- 1400141
TI  - Is hair pulling benign?

PMID- 1400142
TI  - Control groups in research.

PMID- 1400143
TI  - More on clozapine.

PMID- 1400144
TI  - Metoprolol for aggression.

PMID- 1400145
TI  - Detecting clustered microcalcifications in the female breast: secondary digitized
      images versus mammograms.
AB  - We compared the detection of clustered microcalcifications by means of
      conventional mammograms and by means of secondary digitized images with a spatial
      resolution of 2048 x 1684 pixels and a contrast resolution of 12 bit. A Receiver
      Operating Characteristic (ROC) study was carried out using a cadaver breast
      showing phantom microcalcifications. A set of 100 mammograms was evaluated by two
      experienced senior radiologists. The ROC scores obtained with the digital images
      were 10% lower than those obtained with the conventional images. This difference
      however does not reach statistical significance. The use of a digital zoom
      function based on pixel duplication is also investigated. This zoom function does
      not produce a change in the diagnostic accuracy of the digital method. Attention
      is also paid to the advantages and disadvantages encountered by the radiologists
      when working on the digital viewing system. The most important drawback seems to
      be that it is considerably more time consuming than the conventional procedure,
      and this is especially due to the long loading time of the images and to the
      absence of window and level preselections.

PMID- 1400146
TI  - Acute colonic pseudo-obstruction.
AB  - We present two cases of acute colonic pseudo-obstruction, one complicated with
      perforation. Orthopedic surgery was the pathogenetic factor in both cases.
      Recovery was successful in both patients after appropriate treatment. The
      importance of conventional X-ray techniques, and more specially the plain X-ray
      of the abdomen, is stressed regarding early diagnosis and follow-up.

PMID- 1400147
TI  - Magnetic resonance imaging of extrapontine lesions in central pontine
      myelinolysis.
AB  - A rare case of central pontine myelinolysis and associated extrapontine
      myelinolysis is presented. The MR findings confirmed the observations reported in
      recent papers.

PMID- 1400148
TI  - Telangiectatic osteogenic sarcoma: an unusual presentation.
AB  - The authors present a case of telangiectatic osteogenic sarcoma of unusual
      radiographic presentation. The lesion presents as a slow growing, rather "benign"
      tumor, while most osteosarcomas usually present as osteolytic lesions of which
      the radiological aspect allows the diagnosis of malignancy with certainty.

PMID- 1400149
TI  - Peritoneal seeding of a cerebral malignant astrocytoma via a ventriculo
      peritoneal shunt.
AB  - Except for glioblastomas, metastases of astrocytomas and of intracerebral tumors
      are in general very rare. It is well known that the process of spreading can be
      provoked or accelerated by surgical procedures. The presented patient, with the
      initial diagnosis of grade III astrocytoma developed peritoneal metastases after
      placement of a ventriculo-peritoneal shunt.

PMID- 1400151
TI  - Elastofibroma dorsi: CT, MR and pathologic study in a new case.
AB  - As reported before elastofibroma dorsi is a rare benign tumor of elastic
      connective tissue with typical clinical and suggestive radiological features. We
      evaluated the CT and MR characteristics of this periscapular lesion in a new
      case, before and after contrast enhancement, and tried to determine in how far
      the nature and extent of the tumor can be predicted.

PMID- 1400152
TI  - MR imaging of tuberculous spondylitis.
AB  - This case report describes a patient presenting with symptoms of progressive
      paresis of both legs. An X-ray of the thorax demonstrated an aspect consistent
      with miliary tuberculosis. Magnetic resonance imaging (MRI) of the thoracic spine
      revealed medullary compression. The patient underwent a laminectomy and the
      diagnosis of spinal epidural tuberculoma was made. The patient has been treated
      with isoniazid, rifampicin and pyrazinamide. After a period of six months, she
      made a complete recovery.

PMID- 1400150
TI  - Aneurysm of the extrahepatic portal vein associated with segmental portal
      hypertension and spontaneous porto-caval shunting through the inferior mesenteric
      vein.
AB  - A case of a congenital aneurysm of the extrahepatic portal vein is reported. It
      was complicated by segmental portal hypertension of the territory of the inferior
      mesenteric vein, which was a pathway for spontaneous porto-caval shunting.

PMID- 1400153
TI  - A conjugation procedure for Bdellovibrio bacteriovorus and its use to identify
      DNA sequences that enhance the plaque-forming ability of a spontaneous host
      independent mutant.
AB  - Wild-type bdellovibrios are obligate intraperiplasmic parasites of other gram
      negative bacteria. However, spontaneous mutants that can be cultured in the
      absence of host cells occur at a frequency of 10(-6) to 10(-7). Such host
      independent (H-I) mutants generally display diminished intraperiplasmic-growth
      capabilities and form plaques that are smaller and more turbid than those formed
      by wild-type strains on lawns of host cells. An analysis of the gene(s)
      responsible for the H-I phenotype should provide significant insight into the
      nature of Bdellovibrio host dependence. Toward this end, a conjugation procedure
      to transfer both IncQ and IncP vectors from Escherichia coli to Bdellovibrio
      bacteriovorus was developed. It was found that IncQ-type plasmids were capable of
      autonomous replication in B. bacteriovorus, while IncP derivatives were not.
      However, IncP plasmids could be maintained in B. bacteriovorus via homologous
      recombination through cloned B. bacteriovorus DNA sequences. It was also found
      that genomic libraries of wild-type B. bacteriovorus 109J DNA constructed in the
      IncP cosmid pVK100 were stably maintained in E. coli; those constructed in the
      IncQ cosmid pBM33 were unstable. Finally, we used the conjugation procedure and
      the B. bacteriovorus libraries to identify a 5.6-kb BamHI fragment of wild-type
      B. bacteriovorus DNA that significantly enhanced the plaque-forming ability of an
      H-I mutant, B. bacteriovorus BB5.

PMID- 1400154
TI  - Identification of a Bdellovibrio bacteriovorus genetic locus, hit, associated
      with the host-independent phenotype.
AB  - Bdellovibrios invade and grow within the periplasmic space of suitable gram
      negative bacteria. Wild-type bdellovibrios are obligately dependent on host cells
      for growth, but spontaneous host-independent (H-I) mutants that grow axenically
      on standard rich culture media can be isolated. Such mutants generally retain the
      ability to grow intraperiplasmically, although the plaques that they produce on
      lawns of host cells are smaller and more turbid than those produced by wild-type
      bdellovibrios. Here, we identify the first genetic locus associated with the H-I
      phenotype: hit (host interaction). We show that three individual H-I mutants
      suffered mutations at the hit locus and that recombination of wild-type hit
      sequences into the genomes of the H-I mutants greatly enhanced their plaquing
      ability. DNA sequence analysis localized the hit mutation in each of the H-I
      mutants to a 135-bp region of the genome. Mutations at hit may not fully account
      for the H-I phenotype, however, as recombination of wild-type hit sequences into
      the genomes of the H-I mutants had little effect on the axenic-growth phenotype
      of the mutants. Possible explanations for this result and potential roles for the
      hit locus are discussed.

PMID- 1400155
TI  - The Caulobacter crescentus flaFG region regulates synthesis and assembly of
      flagellin proteins encoded by two genetically unlinked gene clusters.
AB  - At a specific time in the Caulobacter crescentus cell cycle, a single flagellar
      filament and multiple receptor sites for the swarmer-specific phage phi Cbk are
      assembled at one pole of the predivisional cell. One cluster of genes required
      for this morphogenesis, the flaYG region, includes the flgJKL genes, which encode
      structural proteins of the flagellar filament. These flagellin genes are flanked
      by genes required for filament assembly, the flaYE genes at one end and the flaF
      flbT-flbA-flaG genes at the other. In this study, we characterized mutants
      carrying large chromosomal deletions within this region. Several of these strains
      are phi CbK resistant and produce a novel 22-kDa flagellin that is not assembled
      into flagella. Merodiploid strains containing either the entire flaFG region or
      individual fla transcription units from this region were constructed. These
      strains were used to correlate the presence or absence of specific gene products
      to changes in flagellin synthesis, filament assembly, or phage sensitivity. As a
      result of these studies, we were able to conclude that (i) the production of the
      22-kDa flagellin results from the absence of the flbA and flaG gene products,
      which appear to be components of a flagellin-processing pathway common to the 25
      , 27-, and 29-kDa flagellins; (ii) flbT negatively modulates the synthesis of the
      27- and 25-kDa flagellins from two genetically unlinked gene clusters; (iii) flgL
      is the only flagellin gene able to encode the 27-kDa flagellin, and this
      flagellin appears to be required for the efficient assembly of the 25-kDa
      flagellins; (iv) flaF is required for filament assembly; and (v) phi CbK
      resistance results from the deletion of at least two genes in the flaFG region.

PMID- 1400156
TI  - Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR
      protein triggers redox-inducible expression of the soxS regulatory gene.
AB  - Escherichia coli responds to the redox stress imposed by superoxide-generating
      agents such as paraquat by activating the synthesis of as many as 80
      polypeptides. Expression of a key group of these inducible proteins is controlled
      at the transcriptional level by the soxRS locus (the soxRS regulon). A two-stage
      control system was hypothesized for soxRS, in which an intracellular redox signal
      would trigger the SoxR protein as a transcriptional activator of the soxS gene
      and the resulting increased levels of SoxS protein would activate transcription
      of the various soxRS regulon genes (B. Demple and C.F. Amabile Cuevas, Cell
      67:837-839, 1990). We have constructed operon fusions of the E. coli lac genes to
      the soxS promoter to monitor soxS transcription. Expression from the soxS
      promoter is strongly inducible by paraquat in a manner strictly dependent on a
      functional soxR gene. Several other superoxide-generating agents also trigger
      soxR(+)-dependent soxS expression, and the inductions by paraquat and phenazine
      methosulfate were dependent on the presence of oxygen. Numerous other oxidative
      stress agents (H2O2, gamma rays, heat shock, etc.) failed to induce soxS, while
      aerobic growth of superoxide dismutase-deficient bacteria triggered soxR
      dependent soxS expression. These results indicate a specific redox signal for
      soxS induction. A direct role for SoxR protein in the activation of the soxS gene
      is indicated by band-shift and DNase I footprinting experiments that demonstrate
      specific binding of the SoxR protein in cell extracts to the soxS promoter. The
      mode of SoxR binding to DNA appears to be similar to that of its homolog MerR in
      that the SoxR footprint spans the -10 to -35 region of the soxS promoter.

PMID- 1400157
TI  - Melting during steady-state transcription of the rrnB P1 promoter in vivo and in
      vitro.
AB  - The rRNA rrnB P1 promoter was probed with the single-strand-selective reagent
      potassium permanganate during steady-state transcription in vitro and in vivo. In
      both cases, a weak but significant level of permanganate sensitivity was
      observed, which was not changed by treatment with rifampin. In contrast, static
      studies showed that rifampin strongly affects the very high level signal
      associated with polymerases that have used ATP and CTP as initiating nucleotides.
      We infer that the permanganate sensitivity associated with steady-state
      transcription is due to polymerases that have not yet used ATP and CTP. The slow
      and regulated step during rrnB P1 transcription may be the use of the initiating
      nucleotides to catalyze stable opening of the promoter DNA.

PMID- 1400158
TI  - Identification, sequence analysis, and expression of a Corynebacterium glutamicum
      gene cluster encoding the three glycolytic enzymes glyceraldehyde-3-phosphate
      dehydrogenase, 3-phosphoglycerate kinase, and triosephosphate isomerase.
AB  - To investigate a possible chromosomal clustering of glycolytic enzyme genes in
      Corynebacterium glutamicum, a 6.4-kb DNA fragment located 5' adjacent to the
      structural phosphoenolpyruvate carboxylase (PEPCx) gene ppc was isolated.
      Sequence analysis of the ppc-proximal part of this fragment identified a cluster
      of three glycolytic genes, namely, the glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) gene gap, the 3-phosphoglycerate kinase (PGK) gene pgk, and the
      triosephosphate isomerase (TPI) gene tpi. The four genes are organized in the
      order gap-pgk-tpi-ppc and are separated by 215 bp (gap and pgk), 78 bp (pgk and
      tpi), and 185 bp (tpi and ppc). The predicted gene product of gap consists of 336
      amino acids (M(r) of 36,204), that of pgk consists of 403 amino acids (M(r) of
      42,654), and that of tpi consists of 259 amino acids (M(r) of 27,198). The amino
      acid sequences of the three enzymes show up to 62% (GAPDH), 48% (PGK), and 44%
      (TPI) identity in comparison with respective enzymes from other organisms. The
      gap, pgk, tpi, and ppc genes were cloned into the C. glutamicum-Escherichia coli
      shuttle vector pEK0 and introduced into C. glutamicum. Relative to the wild type,
      the recombinant strains showed up to 20-fold-higher specific activities of the
      respective enzymes. On the basis of codon usage analysis of gap, pgk, tpi, and
      previously sequenced genes from C. glutamicum, a codon preference profile for
      this organism which differs significantly from those of E. coli and Bacillus
      subtilis is presented.

PMID- 1400159
TI  - Transcription of the Bacillus subtilis sacX and sacY genes, encoding regulators
      of sucrose metabolism, is both inducible by sucrose and controlled by the DegS
      DegU signalling system.
AB  - The adjacent sacX and sacY genes are involved in sucrose induction of the
      Bacillus subtilis sacB gene by an antitermination mechanism. sacB, encoding the
      exoenzyme levansucrase, is also subject to regulation by the DegS-DegU signalling
      system. Using sacXY'-lacZ and sacX'-lacZ fusions, we show that the transcription
      of the sacX and sacY genes is both inducible by sucrose and regulated by DegU.
      sacX and sacY appear to constitute an operon, since the deletion of the sacX
      leader region abolished the expression of a sacXY'-lacZ fusion. The degU
      dependent promoter was located by deletion analysis and reverse transcriptase
      mapping 300 nucleotides upstream from the sacX initiator codon. Sucrose induction
      of the sacX'-lacZ fusion requires either SacY or the homologous SacT
      antiterminator, which is involved in sucrose induction of the intracellular
      sucrase gene (sacPA operon). Sequence analysis of the sacX leader region revealed
      (20 nucleotides downstream from the transcription start site) a putative binding
      site for these regulators; however, no structure resembling a rho-independent
      terminator could be found overlapping this site, unlike the situation for sacPA
      and sacB. Deletion of a segment of the leader region located 100 nucleotides
      downstream from this site led to constitutive expression of the sacXY'-lacZ and
      sacX'-lacZ fusions. These results suggest that the mechanism of sucrose induction
      of sacXY is different from that of sacPA and sacB.

PMID- 1400160
TI  - The NodD protein does not bind to the promoters of inducible nodulation genes in
      extracts of bacteroids of Rhizobium leguminosarum biovar viciae.
AB  - In a previous study, we showed that in bacteroids, transcription of the inducible
      nod genes does not occur and expression of nodD is decreased by 65% (H. R. M.
      Schlaman, B. Horvath, E. Vijgenboom, R.J.H. Okker, and B. J. J. Lugtenberg, J.
      Bacteriol. 173:4277-4287, 1991). In the present study, we show, using gel
      retardation, that in crude extracts of bacteroids of Rhizobium leguminosarum
      biovar (bv.) viciae, NodD protein does not bind to the nodF, nodM, and nodO box
      and that it binds only weakly to the nodA box. Binding of NodD from bacteroids to
      nod box DNA could be restored by mild proteinase K treatment, indicating that
      NodD is present in bacteroids in an altered form or complex which prevents its
      binding to nod box DNA. In addition, a novel nodA box DNA-protein complex was
      found which is specific for the nodA promoter region. This novel complex was
      formed neither with material from cultured bacterial cells nor with an extract
      from uninfected roots, and it did not contain NodD but another protein. These
      results are consistent with the hypothesis that the protein present in the novel
      retardation complex acts as a transcriptional repressor causing the decreased
      nodD expression in bacteroids. Such a repressor also explains the lack of
      nodABCIJ transcription despite the weak NodD binding to the nodA box.

PMID- 1400161
TI  - Mutations that impair swarming motility in Serratia marcescens 274 include but
      are not limited to those affecting chemotaxis or flagellar function.
AB  - Serratia marcescens exists in two cell forms and displays two kinds of motility
      depending on the type of growth surface encountered (L. Alberti and R. M.
      Harshey, J. Bacteriol. 172:4322-4328, 1990). In liquid medium, the bacteria are
      short rods with few flagella and show classical swimming behavior. Upon growth on
      a solid surface (0.7 to 0.85% agar), they differentiate into elongated,
      multinucleate, copiously flagellated forms that swarm over the agar surface. The
      flagella of swimmer and swarmer cells are composed of the same flagellin protein.
      We show in this study that disruption of hag, the gene encoding flagellin,
      abolishes both swimming and swarming motility. We have used transposon mini-Mu
      lac kan to isolate mutants of S. marcescens defective in both kinds of motility.
      Of the 155 mutants obtained, all Fla- mutants (lacking flagella) and Mot- mutants
      (paralyzed flagella) were defective for both swimming and swarming, as expected.
      All Che- mutants (chemotaxis defective) were also defective for swarming,
      suggesting that an intact chemotaxis system is essential for swarming. About one
      third of the mutants were specifically affected only in swarming. Of this class,
      a large majority showed active "swarming motility" when viewed through the
      microscope (analogous to the active "swimming motility" of Che- mutants) but
      failed to show significant movement away from the site of initial inoculation on
      a macroscopic scale. These results suggest that bacteria swarming on a solid
      surface require many genes in addition to those required for chemotaxis and
      flagellar function, which extend the swarming movement outward. We also show in
      this study that nonflagellate S. marcescens is capable of spreading rapidly on
      low-agar media.

PMID- 1400162
TI  - Bacteriophage P1 gene 10 is expressed from a promoter-operator sequence
      controlled by C1 and Bof proteins.
AB  - Gene 10 of bacteriophage P1 encodes a regulatory function required for the
      activation of P1 late promoter sequences. In this report cis and trans regulatory
      functions involved in the transcriptional control of gene 10 are identified.
      Plasmid-borne fusions of gene 10 to the indicator gene lacZ were constructed to
      monitor expression from the gene 10 promoter. Production of gp10-LacZ fusion
      protein became measurable at about 15 min after prophage induction, whereas no
      expression was observed during lysogenic growth. The activity of an Escherichia
      coli-like promoter, Pr94, upstream of gene 10, was confirmed by mapping the
      initiation site of transcription in primer extension reactions. Two phage-encoded
      proteins cooperate in the trans regulation of transcription from Pr94: C1
      repressor and Bof modulator. Both proteins are necessary for complete repression
      of gene 10 expression during lysogeny. Under conditions that did not ensure
      repression by C1 and Bof, the expression of gp10-LacZ fusion proteins from Pr94
      interfered with transformation efficiency and cell viability. Results of in vitro
      DNA-binding studies confirmed that C1 binds specifically to an operator sequence,
      Op94, which overlaps the -35 region of Pr94. Although Bof alone does not bind to
      DNA, together with C1 it increases the efficiency of the repressor-operator
      interaction. These results are in line with the idea that gp10 plays the role of
      mediator between early and late gene transcription during lytic growth of
      bacteriophage P1.

PMID- 1400163
TI  - The proper ratio of FtsZ to FtsA is required for cell division to occur in
      Escherichia coli.
AB  - Interactions among cell division genes in Escherichia coli were investigated by
      examining the effect on cell division of increasing the expression of the ftsZ,
      ftsA, or ftsQ genes. We determined that cell division was quite sensitive to the
      levels of FtsZ and FtsA but much less so to FtsQ. Inhibition of cell division due
      to an increase in FtsZ could be suppressed by an increase in FtsA. Inhibition of
      cell division due to increased FtsA could be suppressed by an increase in FtsZ.
      In addition, although wild-type strains were relatively insensitive to
      overexpression of ftsQ, we observed that cell division was sensitized to ftsQ
      overexpression in ftsI, ftsA, and ftsZ mutants. Among these, the ftsI mutant was
      the most sensitive. These results suggest that these gene products may interact
      and that the proper ratio of FtsZ to FtsA is critical for cell division to occur.

PMID- 1400165
TI  - Structure, function, and fate of the BlaR signal transducer involved in induction
      of beta-lactamase in Bacillus licheniformis.
AB  - The membrane-spanning protein BlaR is essential for the induction of beta
      lactamase in Bacillus licheniformis. Its nature and location were confirmed by
      the use of an antiserum specific for its carboxy-terminal penicillin sensor, its
      function was studied by genetic dissection, and the structure of the penicillin
      sensor was derived from hydrophobic cluster analysis of the amino acid sequence
      by using, as a reference, the class A beta-lactamases with known three
      dimensional structures. During the first 2 h after the addition of the beta
      lactam inducer, full-size BlaR, bound to the plasma membrane, is produced, and
      then beta-lactamase is produced. By 2 h after induction, BlaR is present in
      various (membrane-bound and cytosolic) forms, and there is a gradual decrease in
      beta-lactamase production. The penicillin sensors of BlaR and the class D beta
      lactamases show strong similarities in primary structures. They appear to have
      the same basic spatial disposition of secondary structures as that of the class A
      beta-lactamases, except that they lack several alpha helices and, therefore, have
      a partially uncovered five-stranded beta sheet and a more readily accessible
      active site. Alterations of BlaR affecting conserved secondary structures of the
      penicillin sensor and specific sites of the transducer annihilate beta-lactamase
      inducibility.

PMID- 1400164
TI  - Nucleotide and deduced amino acid sequences of the lacR, lacABCD, and lacFE genes
      encoding the repressor, tagatose 6-phosphate gene cluster, and sugar-specific
      phosphotransferase system components of the lactose operon of Streptococcus
      mutans.
AB  - The complete nucleotide sequences of lacRABCDF and partial nucleotide sequence of
      lacE from the lactose operon of Streptococcus mutans are presented. Comparison of
      the streptococcal lac determinants with those of Staphylococcus aureus and
      Lactococcus lactis indicate exceptional protein and nucleotide identity. The
      deduced polypeptides also demonstrate significant, but lower, sequence similarity
      with the corresponding lactose proteins of Lactobacillus casei. Additionally,
      LacR has sequence homology with the repressor (DeoR) of the Escherichia coli
      deoxyribonucleotide operon, while LacC is similar to phosphokinases (FruK and
      PfkB) from E. coli. The primary translation products of the lacRABCDFE genes are
      polypeptides of 251 (M(r) 28,713), 142 (M(r) 15,610), 171 (M(r) 18,950), 310
      (M(r) 33,368), 325 (M(r) 36,495), 104 (M(r) 11,401), and 123 (NH2-terminal) amino
      acids, respectively. As inferred from their direct homology to the staphylococcal
      lac genes, these determinants would encode the repressor of the streptococcal
      lactose operon (LacR), galactose-6-phosphate isomerase (LacA and LacB), tagatose
      6-phosphate kinase (LacC), tagatose-1,6-bisphosphate aldolase (LacD), and the
      sugar-specific components enzyme III-lactose (LacF) and enzyme II-lactose (LacE)
      of the S. mutans phosphoenolpyruvate-dependent phosphotransferase system. The
      nucleotide sequence encompassing the S. mutans lac promoter appears to contain
      repeat elements analogous to those of S. aureus, suggesting that repression and
      catabolite repression of the lactose operons may be similar in these organisms.

PMID- 1400167
TI  - Functional replacement of genes for individual polyketide synthase components in
      Streptomyces coelicolor A3(2) by heterologous genes from a different polyketide
      pathway.
AB  - Streptomyces coelicolor A3(2) and Streptomyces violaceoruber Tu22 produce the
      antibiotics actinorhodin and granaticin, respectively. Both the aglycone of
      granaticin and the half-molecule of actinorhodin are derived from one acetyl
      coenzyme A starter unit and seven malonyl coenzyme A extender units via the
      polyketide pathway to produce benzoisochromane quinone moieties with identical
      structures (except for the stereochemistry at two chiral centers). In S.
      coelicolor and S. violaceoruber, the type II polyketide synthase (PKS) is encoded
      by clusters of five and six genes, respectively. We complemented a series of S.
      coelicolor mutants (act) defective in different components of the PKS (actI for
      carbon chain assembly, actIII for ketoreduction, and actVII for cyclization
      dehydration) by the corresponding genes (gra) from S. violaceoruber introduced in
      trans on low-copy-number plasmids. This procedure showed that four of the act PKS
      components could be replaced by a heterologous gra protein to give a functional
      PKS. The analysis also served to identify which of three candidate open reading
      frames (ORFs) in the actI region had been altered in each of a set of 13 actI
      mutants. It also proved that actI-ORF2 (whose putative protein product shows
      overall similarity to the beta-ketoacyl synthase encoded by actI-ORF1 but whose
      function is unclear) is essential for PKS function. Mutations in each of the four
      complemented act genes (actI-ORF1, actI-ORF2, actIII, and actVII) were cloned and
      sequenced, revealing a nonsense or frameshift mutation in each mutant.

PMID- 1400166
TI  - In vitro activation of dinitrogenase reductase from the cyanobacterium Anabaena
      variabilis (ATCC 29413).
AB  - Nitrogenase of the heterocystous cyanobacterium Anabaena variabilis was
      inactivated in vivo (S. Reich, H. Almon, and P. Boger, FEMS Microbiol. Lett.
      34:53-56, 1986). Partially purified and modified (inactivated) dinitrogenase
      reductase (Fe-protein) of such cells was reactivated by isolated membrane
      fractions of A. variabilis or of Rhodospirillum rubrum, and acetylene reduction
      was measured. Reactivation requires ATP, Mg2+, and Mn2+. The activating principle
      is localized in the heterocyst and was found effective only when prepared from
      cells exhibiting active nitrogenase. It also restores the activity of modified Fe
      protein from R. rubrum.

PMID- 1400168
TI  - Selective synthesis and labeling of the polysialic acid capsule in Escherichia
      coli K1 strains with mutations in nanA and neuB.
AB  - The enzymes required for polysialic acid capsule synthesis in Escherichia coli K1
      are encoded by region 2 neu genes of the multigenic kps cluster. To facilitate
      analysis of capsule synthesis and translocation, an E. coli K1 strain with
      mutations in nanA and neuB, affecting sialic acid degradation and synthesis,
      respectively, was constructed by transduction. The acapsular phenotype of the
      mutant was corrected in vivo by exogenous addition of sialic acid. By blocking
      sialic acid degradation, the nanA mutation allows intracellular metabolite
      accumulation, while the neuB mutation prevents dilution by the endogenous sialic
      acid pool and allows capsule synthesis to be controlled experimentally by the
      exogenous addition of sialic acid to the growth medium. Complementation was
      detected by bacteriophage K1F adsorption or infectivity assays. Polysialic acid
      translocation was observed within 2 min after addition of sialic acid to the
      growth medium, demonstrating the rapidity in vivo of sialic acid transport,
      activation, and polymerization and translocation of polysaccharide to the cell
      surface. Phage adsorption was not inhibited by chloramphenicol, demonstrating
      that de novo protein synthesis was not required for polysialic acid synthesis or
      translocation at 37 degrees C. Exogenous radiolabeled sialic acid was
      incorporated exclusively into capsular polysaccharide. The polymeric nature of
      the labeled capsular material was confirmed by gel permeation chromatography and
      susceptibility of sialyl polymers to K1F endo-N-acylneuraminidase. The ability to
      experimentally manipulate capsule expression provides new approaches for
      investigating polysialic acid synthesis and membrane translocation mechanisms.

PMID- 1400169
TI  - A three-start helical sheath on the flagellar filament of Caulobacter crescentus.
AB  - An unusual feature in preparations of the Caulobacter crescentus flagellar
      filaments is that some filaments are surrounded by a set of three windings that
      form a sheath. We provide evidence that the sheath is composed of subunits having
      a molecular mass of 24,000 Da. We suggest that the sheath could be composed of
      protofilaments of flagellin wound around the filament.

PMID- 1400170
TI  - Structural characterization and corepressor binding of the Escherichia coli
      purine repressor.
AB  - The Escherichia coli purine repressor, PurR, binds to a 16-bp operator sequence
      and coregulates the genes for de novo synthesis of purine and pyrimidine
      nucleotides, formation of a one-carbon unit for biosynthesis, and deamination of
      cytosine. We have characterized the purified repressor. Chemical cross-linking
      indicates that PurR is dimeric. Each subunit has an N-terminal domain of 52 amino
      acids for DNA binding and a C-terminal 289-residue domain for corepressor
      binding. Each domain was isolated after cleavage by trypsin. Sites for dimer
      formation are present within the corepressor binding domain. The corepressors
      hypoxanthine and guanine bind cooperatively to distinct sites in each subunit.
      Competition experiments indicate that binding of one purine abolishes
      cooperativity and decreases the affinity and the binding of the second
      corepressor. Binding of each corepressor results in a conformation change in the
      corepressor binding domain that was detected by intrinsic fluorescence of three
      tryptophan residues. These experiments characterize PurR as a complex allosteric
      regulatory protein.

PMID- 1400171
TI  - Two promoters for the whiB sporulation gene of Streptomyces coelicolor A3(2) and
      their activities in relation to development.
AB  - Two transcripts corresponding to the whiB sporulation gene of Streptomyces
      coelicolor A3(2) that differed in length at their 5' ends by 164 nucleotides were
      identified by S1 mapping. Their presumptive promoters differed from each other;
      the more downstream, P2, resembled typical prokaryotic promoters (i.e., those
      recognized by the major form of RNA polymerase) at five of six positions in its 
      10 and -35 regions; and the more upstream, P1, was comparably similar, instead,
      to the previously described hrdDp1 promoter (M. J. Buttner, K. F. Chater, and M.
      J. Bibb, J. Bacteriol. 172:3367-3378, 1990) around -40, -10, and +1. In surface
      cultures of the wild-type strain, the abundance of transcripts from the weak P1
      promoter showed no obvious correlation with the developmental stage, whereas
      transcripts from P2 were barely detectable until aerial mycelium was present and
      then became relatively abundant, consistent with the developmental role of whiB.
      Both types of transcript were detected during and, to a lesser extent, after
      rapid growth in liquid culture. In addition, both promoters were utilized in
      vitro by RNA polymerase purified from a liquid culture of S. coelicolor.
      Transcription from P1 and P2 was observed during surface culture in strains
      carrying mutations blocking aerial mycelium formation (bldA and bldB) or the
      formation of spores in aerial mycelium (whiA, whiB, whiG, and whiH). Thus, whiB
      transcription is not severely dependent on any of these developmental genes,
      among which whiG is the determinant of a putative sigma factor specific for, and
      crucial to, sporulation.

PMID- 1400172
TI  - A 14-kilodalton inner membrane protein of Vibrio cholerae biotype e1 tor confers
      resistance to group IV choleraphage infection to classical vibrios.
AB  - Choleraphage phi 149 differentiates the two biotypes, classical and el tor, of
      Vibrio cholerae. This phage cannot replicate in V. cholerae biotype el tor cells
      because the concatemeric DNA intermediates produced are unstable and cannot be
      chased to mature phage DNA. A V. cholerae biotype el tor gene coding for a 14,000
      Da inner membrane protein which destabilizes the concatemeric DNA intermediates
      by hindering their binding to the cell membrane has been identified. Presumably,
      a 22,000-Da V. cholerae biotype el tor protein might also have a role in
      conferring phage phi 149 resistance to cells belonging to the biotype el tor. A
      nucleotide sequence homologous to the 1.2-kb V. cholerae biotype el tor DNA
      coding for both the 14,000- and 22,000-Da proteins is present in all strains of
      classical vibrios but is not transcribed. The nucleotide sequence of the gene
      coding for the 14,000-Da protein has been determined.

PMID- 1400173
TI  - Sequence analysis and characterization of the mobilization region of a broad-host
      range plasmid, pTF-FC2, isolated from Thiobacillus ferrooxidans.
AB  - The nucleotide sequence of a 5,317-bp fragment which includes the region required
      for mobilization of broad-host-range plasmid pTF-FC2 was determined. A region of
      approximately 3.5 kb was required for plasmid mobilization, and oriT was
      localized on a 138-bp fragment. Polypeptides which corresponded in size and
      location to several of the open reading frames were detected in an in vitro
      transcription-translation system. Three open reading frames essential for plasmid
      mobilization and two which affect the mobilization frequency were identified.
      There was a distinct similarity in the sizes, amino acid sequences, and locations
      of the proteins from the mobilization region of pTF-FC2 and the Tra1 region of
      IncP plasmid RP4. Similarity in the structures and sequences of the oriT regions
      was also apparent. A sequence with 37-of-38-bp homology to the inverted repeated
      sequences of Tn21 and an open reading frame with strong homology to the MerR
      regulatory protein was identified outside of the region required for
      mobilization.

PMID- 1400174
TI  - The oriT region of the Agrobacterium tumefaciens Ti plasmid pTiC58 shares DNA
      sequence identity with the transfer origins of RSF1010 and RK2/RP4 and with T
      region borders.
AB  - Ti plasmids of Agrobacterium tumefaciens are conjugal elements whose transfer is
      induced by certain opines secreted from crown galls. On transmissible plasmids,
      DNA transfer initiates within a cis-acting site, the origin of conjugal transfer,
      or oriT. We have localized an oriT on the A. tumefaciens plasmid pTiC58 to a
      region containing the conjugal transfer loci traI and traII and acc, which is the
      locus encoding catabolism of the two conjugal opines, agrocinopines A and B. The
      smallest functional oriT clone, a 65-bp BamHI-ApaI fragment in the recombinant
      plasmid pDCBA60-11, mapped within the traII locus. The nucleotide sequence for a
      665-bp KpnI-EcoRI fragment with oriT activity was determined. DNA sequence
      alignments showed identities between the pTiC58 oriT and the transfer origins of
      RSF1010, pTF1, and RK2/RP4 and with the pTiC58 T-region borders. The RSF1010-like
      sequence on pTiC58 is located in the smallest active oriT clone of pTiC58, while
      the sequence showing identities with the oriT regions of RK2/RP4 and with T
      region borders maps outside this region. Despite their sequence similarities,
      pTiC58 oriT clones were not mobilized by RP4; nor could vectors containing the
      RK2/RP4 oriT region or the oriT-mob region from RSF1010 be mobilized by pTiC58.
      In contrast, other Ti plasmids and a conjugally active Agrobacterium opine
      catabolic plasmid, pAtK84b, efficiently mobilized pTiC58 oriT clones. In
      addition, the RSF1010 derivative, pDSK519, was mobilized at moderate frequencies
      by an Agrobacterium strain harboring only the cryptic plasmid pAtC58 and at very
      low frequencies by an Agrobacterium host that does not contain any detectable
      plasmids.

PMID- 1400175
TI  - A chemotactic signaling surface on CheY defined by suppressors of flagellar
      switch mutations.
AB  - CheY is the response regulator protein that interacts with the flagellar switch
      apparatus to modulate flagellar rotation during chemotactic signaling. CheY can
      be phosphorylated and dephosphorylated in vitro, and evidence indicates that CheY
      P is the activated form that induces clockwise flagellar rotation, resulting in a
      tumble in the cell's swimming pattern. The flagellar switch apparatus is a
      complex macromolecular structure composed of at least three gene products, FliG,
      FliM, and FliN. Genetic analysis of Escherichia coli has identified fliG and fliM
      as genes in which mutations occur that allele specifically suppress cheY
      mutations, indicating interactions among these gene products. We have generated a
      class of cheY mutations selected for dominant suppression of fliG mutations.
      Interestingly, these cheY mutations dominantly suppressed both fliG and fliM
      mutations; this is consistent with the idea that the CheY protein interacts with
      both switch gene products during signaling. Biochemical characterization of wild
      type and suppressor CheY proteins did not reveal altered phosphorylation
      properties or evidence for phosphorylation-dependent CheY multimerization. These
      data indicate that suppressor CheY proteins are specifically altered in the
      ability to transduce chemotactic signals to the switch at some point subsequent
      to phosphorylation. Physical mapping of suppressor amino acid substitutions on
      the crystal structure of CheY revealed a high degree of spatial clustering,
      suggesting that this region of CheY is a signaling surface that transduces
      chemotactic signals to the switch.

PMID- 1400177
TI  - New mutations in and around the L2 disordered loop of the RecA protein modulate
      recombination and/or coprotease activity.
AB  - The RecA protein plays a key role in Escherichia coli recombination and DNA
      repair. We have created new recA mutants with mutations in the vicinity of the
      recA430 mutation (Gly-204----Ser) which is known to affect RecA coprotease
      activity. Mutants carrying recA659 or recA611, located 3 and 7 amino acids
      downstream of residue 204, respectively, lose all RecA activities, while the
      mutant carrying recA616, which is located at 12 amino acids from this residue,
      keeps the coprotease activity but is unable to promote recombination.
      Complementation experiments show that both mutations recA611 and recA659 are
      dominant over the wild-type or recA430 allele while recA616 seems to be recessive
      to recA+ and dominant over recA430. It is suggested that these mutations are
      located in RecA domains which direct conformational modifications.

PMID- 1400176
TI  - DnaK, DnaJ, and GrpE are required for flagellum synthesis in Escherichia coli.
AB  - The DnaK, DnaJ, and GrpE heat shock proteins are required for motility of
      Escherichia coli. Cells deleted for dnaK or dnaJ, or with some mutations in the
      dnaK or grpE gene, are nonmotile, lack flagella, exhibit a 10- to 20-fold
      decrease in the rate of synthesis of flagellin, and show reduced rates of
      transcription of both the flhD master operon (encoding FlhD and FlhC) and the
      fliA operon (encoding sigma F). Genetic studies suggest that DnaK and DnaJ define
      a regulatory pathway affecting flhD and fliA synthesis that is independent of
      cyclic AMP-catabolite gene activator protein or the chemotaxis system.

PMID- 1400178
TI  - Effects of site-directed mutations on processing and activities of penicillin G
      acylase from Escherichia coli ATCC 11105.
AB  - Penicillin G acylase from Escherichia coli ATCC 11105 is synthesized from its
      precursor polypeptide into a catalytically active heterodimer via a complex
      posttranslational processing pathway. Substitutions in the pair of aminoacyl
      residues at the cleavage site for processing the small and large subunits were
      made. Their processing phenotypes and penicillin G acylase activities were
      analyzed. By the introduction of a prolyl residue at either position, the
      processing of the small subunit was blocked without a change in enzymatic
      activity. Four other substitutions had no effect. At the site for processing the
      large subunit, four substitutions out of the seven examined blocked processing.
      In general, penicillin G acylase activity seemed to be proportional to the
      efficiency of the large-subunit-processing step. Ser-290 is an amino acid
      critical for processing and also for the enzymatic activity of penicillin G
      acylase. In the mutant pAATC, in which Ser-290 is mutated to Cys, the precursor
      is processed, but there is no detectable enzymatic activity. This suggests that
      there is a difference in the structural requirements for the processing pathway
      and for enzymatic activity. Recombination analysis of several mutants
      demonstrated that the small subunit can be processed only when the large subunit
      is processed first. Some site-directed mutants from which signal peptides were
      removed showed partial processing phenotypes and reduced enzymatic activities.
      Their expression showed that the prerequisite for penicillin G acylase activity
      is the efficient processing of the large subunit and that the maturation of the
      small subunit does not affect the enzymatic activity.

PMID- 1400179
TI  - Maturation of membrane-bound hydrogenase of Alcaligenes eutrophus H16.
AB  - The formation of the catalytically active membrane-bound hydrogenase (MBH) of
      Alcaligenes eutrophus H16 requires the genes for the small and large subunits of
      the enzyme (hoxK and hoxG, respectively) and an accompanying set of accessory
      genes (C. Kortl ke, K. Horstmann, E. Schwartz, M. Rohde, R. Binsack, and B.
      Friedrich, J. Bacteriol. 174:6277-6289, 1992). Other genes located in the
      adjacent pleiotropic region are also required. In the absence of these genes, MBH
      is synthesized but is catalytically inactive. Immunological analyses revealed
      that cells containing active MBH produced the small and large subunits of the
      enzyme in two distinct conformations each; only one of each, presumably the
      immature form, occurred in cells devoid of MBH activity. The results suggest that
      the conversion of the two subunits into the catalytically active membrane
      associated heterodimer depends on specific maturation processes mediated by hox
      genes.

PMID- 1400181
TI  - Size and stability of the genomes of the myxobacteria Stigmatella aurantiaca and
      Stigmatella erecta.
AB  - Genomic DNA of Stigmatella aurantiaca DW 4/3.1 was restricted with the rare
      cutting endonucleases AseI and SpeI. The restriction pattern derived is composed
      of 33 AseI and 25 SpeI fragments, whose total size amounts to approximately 9,350
      kbp. Genomic fingerprint analysis of chromosomal DNA from several S. aurantiaca
      isolates further revealed five completely different SpeI and AseI fingerprints
      and one distinct fingerprint for Stigmatella erecta. In addition, minor
      variations between the genome sizes of these isolates were observed.

PMID- 1400180
TI  - Molybdenum cofactor (chlorate-resistant) mutants of Klebsiella pneumoniae M5al
      can use hypoxanthine as the sole nitrogen source.
AB  - Selection for chlorate resistance yields mol (formerly chl) mutants with defects
      in molybdenum cofactor synthesis. Complementation and genetic mapping analyses
      indicated that the Klebsiella pneumoniae mol genes are functionally homologous to
      those of Escherichia coli and occupy analogous genetic map positions.
      Hypoxanthine utilization in other organisms requires molybdenum cofactor as a
      component of xanthine dehydrogenase, and thus most chlorate-resistant mutants
      cannot use hypoxanthine as a sole source of nitrogen. Surprisingly, the K.
      pneumoniae mol mutants and the mol+ parent grew equally well with hypoxanthine as
      the sole nitrogen source, suggesting that K. pneumoniae has a molybdenum cofactor
      independent pathway for hypoxanthine utilization.

PMID- 1400182
TI  - DNA polymerase I modulates inducible stable DNA replication in Escherichia coli.
AB  - Mutants of Escherichia coli lacking RNase HI activity and cells induced for the
      SOS response express modes of DNA replication independent of protein synthesis,
      called constitutive and induced stable DNA replication, respectively. We report
      here that mutants deleted for the polA gene express induced stable DNA
      replication at approximately 25-fold the rate of wild-type cells, whereas
      constitutive stable DNA replication is not enhanced.

PMID- 1400183
TI  - Inhibition of cell division initiation by an imbalance in the ratio of FtsA to
      FtsZ.
AB  - Elevated levels of FtsA protein block cell division at a very early stage,
      similar to that caused by inhibition of the action of FtsZ. In contrast,
      overexpression of FtsA and FtsZ together does not block division. A specific
      ratio of FtsA to FtsZ protein, therefore, is required for cell division.

PMID- 1400184
TI  - Characterization of the gill symbiont of Thyasira flexuosa (Thyasiridae:
      Bivalvia) by use of polymerase chain reaction and 16S rRNA sequence analysis.
AB  - Comparative molecular sequence (16S rRNA) analysis methods were used to identify
      and characterize the symbionts of Thyasira flexuosa independently of pure culture
      techniques and to compare these symbionts with the previously reported putative
      symbiont isolate, Thiobacillus thyasiris TG-2 (A. P. Wood and D. P. Kelly, Arch.
      Microbiol. 152:160-166, 1989). Polymerase chain reaction amplification using 16S
      rRNA primers specific for eubacteria was used to amplify a single unique sequence
      from the gill tissue of T. flexuosa. This sequence is phylogenetically most
      closely related to the 16S rRNA genes of known symbionts of lucinid clams and is
      distinct from those determined for strain TG-2 and other known bacteria. Strain
      TG-2 most closely resembles a free-living, chemolithoautotrophic bacterium known
      to be associated with the surfaces of thiotrophic bivalve shells, suggesting that
      this strain is a contaminant and not the authentic intracellular symbiont of T.
      flexuosa.

PMID- 1400185
TI  - Characterization of cspB, a Bacillus subtilis inducible cold shock gene affecting
      cell viability at low temperatures.
AB  - A new class of cold shock-induced proteins that may be involved in an adaptive
      process required for cell viability at low temperatures or may function as
      antifreeze proteins in Escherichia coli and Saccharomyces cerevisiae has been
      identified. We purified a small Bacillus subtilis cold shock protein (CspB) and
      determined its amino-terminal sequence. By using mixed degenerate
      oligonucleotides, the corresponding gene (cspB) was cloned on two overlapping
      fragments of 5 and 6 kb. The gene encodes an acidic 67-amino-acid protein (pI
      4.31) with a predicted molecular mass of 7,365 Da. Nucleotide and deduced amino
      acid sequence comparisons revealed 61% identity to the major cold shock protein
      of E. coli and 43% identity to a family of eukaryotic DNA binding proteins.
      Northern RNA blot and primer extension studies indicated the presence of one cspB
      transcript that was initiated 119 bp upstream of the initiation codon and was
      found to be induced severalfold when exponentially growing B. subtilis cell
      cultures were transferred from 37 degrees C to 10 degrees C. Consistent with this
      cold shock induction of cspB mRNA, a six- to eightfold induction of a cspB
      directed beta-galactosidase synthesis was observed upon downshift in temperature.
      To investigate the function of CspB, we inactivated the cold shock protein by
      replacing the cspB gene in the B. subtilis chromosome with a cat-interrupted copy
      (cspB::cat) by marker replacement recombination. The viability of cells of this
      mutant strain, GW1, at freezing temperatures was strongly affected. However, the
      effect of having no CspB in GW1 could be slightly compensated for when cells were
      preincubated at 10 degrees C before freezing. These results indicate that CspB
      belongs to a new type of stress-inducible proteins that might be able to protect
      B. subtilis cells from damage caused by ice crystal formation during freezing.

PMID- 1400186
TI  - Synthesis of cyclic beta-(1,2)-glucans by Rhizobium leguminosarum biovar trifolii
      TA-1: factors influencing excretion.
AB  - The synthesis of cyclic beta-(1,2)-glucans from UDP-[14C]glucose by a crude
      membrane preparation and whole cells of Rhizobium leguminosarum bv. trifolii TA-1
      was investigated. The crude membrane system needed Mn2+, ATP, and NAD+ for
      optimal activity. Hardly any difference in biosynthetic activity between membrane
      fractions of TA-1 cells grown in the presence (200 mM) or absence of NaCl was
      observed. Whole TA-1 cells grown in the presence of NaCl excreted labeled,
      neutral cyclic beta-(1,2)-glucan during incubation with added UDP-[14C]glucose.
      With NaCl-free cultured TA-1 cells, no excretion was observed; however, after
      these cells were alternately frozen and thawed eight times, they excreted
      glucans. Glucan formation in vitro and glucan excretion by whole cells were
      strongly inhibited in the presence of 50 mg of cyclic glucan per ml (about 15
      mM), indicating that biosynthesis of cyclic beta-(1,2)-glucans in strain TA-1 is
      controlled by end-product inhibition. These observations indicate that TA-1 cells
      become more permeable to cyclic glucans at high NaCl concentrations. The constant
      loss of glucans from cells grown in the presence of 200 mM NaCl prevented end
      product inhibition and resulted in glucan accumulation of up to 1,600 mg/liter in
      the medium.

PMID- 1400187
TI  - Isolation and analysis of a novel inducible pectate lyase gene from the
      phytopathogenic fungus Fusarium solani f. sp. pisi (Nectria haematococca, mating
      population VI).
AB  - A pectate lyase produced by Fusarium solani f. sp. pisi (Nectria haematococca,
      mating population VI) was previously shown to be essential for host infection (M.
      S. Crawford and P. E. Kolattukudy, Arch. Biochem. Biophys. 258:196-205, 1987).
      Pectate lyase genes have not been cloned from any phytopathogenic fungi. A gene,
      designated pelA, encoding an inducible pectate lyase was isolated from F. solani
      f. sp. pisi. A probe was synthesized by polymerase chain reaction with
      oligonucleotide primers based on the known amino acid sequences of two regions of
      the mature protein and first-strand cDNA as template. Both cDNA and the gene were
      isolated and sequenced. That the cloned cDNA represents the previously purified
      pectate lyase is shown by the complete match of the sequences of the N-terminal
      38 amino acid residues and the 20 amino acid residues of an internal peptide with
      the sequence deduced from the cDNA sequence. This lyase sequence shows little
      homology to those of other pectolytic enzymes. The pelA gene shows standard
      characteristics with respect to promoter, intron, and polyadenylation sequences.
      As determined by primer extension and nuclease S1 analysis of the origin of the
      transcription, there are multiple initiation sites clustered in a region of 12
      nucleotides located about 55 bp upstream of the start codon. Northern (RNA) blot
      analysis showed a single band of mRNA at about 1 kb. The pelA gene mRNA was
      detected only when F. solani f. sp. pisi was grown with pectin, and there was no
      detectable transcript accumulation when the fungus was grown with glucose as the
      sole carbon source. When both carbon sources were present, the pelA gene was
      transcribed only after glucose was completely depleted, indicating carbon
      catabolite repression. Moreover, the levels of transcription decreased rapidly
      prior to maximal enzyme accumulation, suggesting a mechanism of self catabolite
      repression.

PMID- 1400188
TI  - Identification of minor fimbrial subunits involved in biosynthesis of K88
      fimbriae.
AB  - The nucleotide sequences of the genes faeF, faeH, faeI, and faeJ encoding K88
      minor fimbrial subunits were determined. Analysis of the primary structure of the
      gene products revealed that all four proteins are synthesized with an amino
      terminal signal sequence. The molecular masses of the mature FaeF, FaeH, FaeI,
      and FaeJ proteins were calculated to be 15,161, 25,461, 24,804, and 25,093 Da,
      respectively. FaeH, FaeI, and FaeJ showed significant homology with FaeG, the
      major fimbrial subunit of K88 fimbriae. Mutations in the respective genes were
      constructed. Analysis of the mutants showed that the minor fimbrial subunits FaeF
      and FaeH play an essential role in the biogenesis but not in the adhesive
      properties of the K88 fimbriae. Mutations in faeI or faeJ had no significant
      effect on K88 production or adhesive capacity. Specific antisera against FaeF and
      FaeH were raised by immunization with hybrid Cro-LacZ-FaeF and Cro-LacZ-FaeH
      proteins. Immunoblotting and immunoelectron microscopy revealed that FaeF and
      FaeH are located in or along the K88 fimbrial structure.

PMID- 1400189
TI  - vacB, a novel chromosomal gene required for expression of virulence genes on the
      large plasmid of Shigella flexneri.
AB  - Shigellae, the causative agents of bacillary dysentery, are capable of adhering
      to and invading epithelial cells and spreading into adjacent cells. A chromosomal
      mutant of Shigella flexneri 2a YSH6000 with reduced invasive capacity was
      isolated by Tn5 insertion mutagenesis. The linkage of the mutant phenotype to the
      Tn5 insertion was determined by P1 phage transduction. The site of the Tn5
      insertion was assigned to a NotI chromosomal restriction map, confirming that the
      virulence-associated locus, designated vacB, is a new locus on the chromosome. In
      the vacB mutant, production of the four plasmid-encoded virulence antigens, IpaB,
      -C, and -D and VirG, decreased to a low level compared with that in the wild
      type. In contrast, levels of transcription of the operons for virG, ipa, region
      3.4, region-5, virF, and virB on the large plasmid, as determined by Northern dot
      blotting, were unaffected in the vacB mutant. Furthermore, transcriptional
      activation of the ipa operon by exploiting a tac promoter could not restore the
      vacB mutant to production of the same levels of the IpaB, -C, and -D proteins as
      those in the wild type, indicating that the vacB locus is involved in expression
      of the vir genes on the large plasmid at the posttranscriptional level. Cloning
      followed by nucleotide sequencing of the vacB region showed it to contain a 2,280
      bp open reading frame encoding an 86.9-kDa protein located 669 bp downstream from
      the 3' end of the open reading frame for the purA gene. Disruption of the vacB
      gene of other serotypes of Shigella spp. and enteroinvasive Escherichia coli
      (EIEC) resulted in reduced expression of virulence phenotypes, indicating that
      the vacB gene encodes a novel type of virulence-associated gene required for the
      full expression of the virulence phenotype of Shigella spp. and EIEC.

PMID- 1400190
TI  - Cloning and nucleotide sequence of celA1, and endo-beta-1,4-glucanase-encoding
      gene from Streptomyces halstedii JM8.
AB  - The celA1 gene encoding an endo-beta-1,4-glucanase from a mesophilic
      actinomycete, strain JM8, identified as Streptomyces halstedii, was cloned and
      expressed in S. lividans JI66. From the nucleotide sequence of a 1.7-kb DNA
      fragment we identified an open reading frame of 963 nucleotides encoding a
      protein of 321 amino acids, starting at TTG (instead of ATG). The Cel1 mature
      enzyme is a protein of 294 amino acids (after signal peptide cleavage) and can be
      included in the beta-glycanase family B (N. R. Gilkes, B. Henrissat, D. G.
      Kilburn, R. C. Miller, Jr., and R. A. J. Warren, Microbiol. Rev. 55:303-315,
      1991). The Cel1 enzyme lacks a cellulose-binding domain as predicted by computer
      analysis of the sequence and confirmed by Avicel binding experiments. The
      promoter region of celA1 was identified by S1 mapping; the -35 region closely
      resembles those of housekeeping Streptomyces promoters. Three imperfectly
      repeated sequences of 15, 15, and 14 nucleotides were found upstream from celA1
      [ATTGGGACCGCTTCC-(N85)-ATTGGGACCGCTTCC-(N2)-TGGGAGC GCTCCCA]; The 14-nucleotide
      sequence has a perfect palindrome identical to that found in several cellulase
      encoding genes from Thermomonospora fusca, an alkalophilic Streptomyces strain,
      and Streptomyces lividans. This sequence has been implicated in the mechanism of
      induction exerted by cellobiose. Using an internal celA1 probe, we detected
      similar genes in several other Streptomyces species, most of them cellulase
      producers.

PMID- 1400191
TI  - Transformational exchanges in the dihydropteroate synthase gene of Neisseria
      meningitidis: a novel mechanism for acquisition of sulfonamide resistance.
AB  - The nucleotide sequences of the chromosomal dihydropteroate synthase (dhps) genes
      in sulfonamide-susceptible and sulfonamide-resistant strains of Neisseria
      meningitidis of serogroups A, B and C were determined. The molecular weights and
      the amino acid sequences showed similarity to those of all other known
      dihydropteroate synthase polypeptides. Sequence comparison of the N. meningitidis
      dhps genes indicated horizontal transfer of DNA segments rather than point
      mutations as the cause for resistance in meningococci. The dhps genes in three of
      four sulfonamide-resistant meningococci contained identical central regions of
      424 bp. Compared with the corresponding genes in susceptible strains, each
      central region included an insert of 6 bp. In one of the sulfonamide-resistant
      strains, the dhps gene was similar to the corresponding genes in the sensitive
      strains in its NH2-terminal and C-terminal parts. Its central region, however,
      was identical to the corresponding regions of two of the other resistant genes,
      and thus it could be seen as a hybrid dhps gene. Transformation experiments and
      mapping of transformed dhps genes indicated the existence of a novel mechanism
      for the dissemination of sulfonamide resistance in N. meningitidis. The origin of
      the resistance-mediating segment of the gene is unknown, but hybridization
      results showed the presence of homologous dhps genes in Neisseria gonorrhoeae and
      N. lactamica but not in N. subflava or Branhamella catarrhalis.

PMID- 1400192
TI  - Molecular genetic analysis of a class B periplasmic-flagellum gene of Treponema
      phagedenis.
AB  - Treponema phagedenis is a host-associated spirochete with multiple polypeptides
      making up its periplasmic flagella (PFs). Each PF has a 39-kDa polypeptide making
      up the sheath (class A PF polypeptide) and two to four antigenically similar 33-
      to 34-kDa polypeptide species making up the core (class B PF polypeptides). A
      genetic analysis of the PF-deficient mutants T-40 and T-55 has shown that the PFs
      are involved in motility. To better understand the synthesis and assembly of
      these complex organelles and to compare the PF genes with those of other
      spirochetes, we cloned and characterized the T. phagedenis flaB2 gene, which
      encodes one class B polypeptide. The flaB2 gene consists of an open reading frame
      of 858 nucleotides capable of encoding a protein of 31.5 kDa. The predicted amino
      acid sequence of the FlaB2 polypeptide was 92% identical to that of T. pallidum
      FlaB2, with a 76% identity at the nucleotide level. These results confirm
      previous immunological and N-terminal-sequence analyses which suggested that the
      PF genes are well conserved in the spirochetes. Primer extension analysis of T.
      phagedenis flaB2 indicated that the start site of transcription was 127
      nucleotides upstream from the ATG initiation codon. Preceding the start site is a
      DNA sequence similar to the sigma 28 consensus promoter sequence commonly found
      associated with motility genes. Northern (RNA) blots probed with a segment of
      flaB2 DNA revealed a 1,000-nucleotide monocistronic transcript in the wild type
      and in PF-deficient mutants T-40 and T-55. DNA sequencing of most of the flaB2
      gene of the mutants revealed no differences from the wild-type gene. Because the
      mutants fail to synthesize detectable class B PF polypeptides yet synthesize
      extensive amounts of flaB2 mRNA, PF synthesis in T. phagedenis is likely to
      involve regulation at the translational level.

PMID- 1400193
TI  - Characterization of translation termination mutations in the spv operon of the
      Salmonella virulence plasmid pSDL2.
AB  - The spv region of the Salmonella virulence plasmids consists of five genes
      located on an 8-kb fragment previously shown to be essential for virulence in
      mice. Four structural genes, spvABCD, form an operon that is transcriptionally
      activated by the spvR gene product in the stationary phase of growth. The role of
      the individual spv genes in the virulence phenotype was tested by isolating
      translation termination linker insertions in each gene. Analysis of proteins
      synthesized in minicells identified each of the spvABCD gene products and
      confirmed the dependence of spv structural gene expression on the SpvR regulatory
      protein. The oligonucleotide insertions in spvA, -B, and -C were shown to be
      nonpolar. Virulence testing indicated that the SpvB protein, regulated by SpvR,
      is essential for Salmonella dublin to cause lethal disease in mice. Inserts in
      spvC and spvD were unstable in vivo for unknown reasons, but these mutants still
      killed mice at slightly higher inocula. Abolition of spvA had no effect on
      virulence in this system.

PMID- 1400195
TI  - An alpha-helical hydrophobic hairpin as a specific determinant in protein-protein
      interaction occurring in Escherichia coli colicin A and B immunity systems.
AB  - A collection of chimeric pore-forming domains between colicins A and B was
      constructed to investigate the specific determinants responsible for recognition
      by the corresponding immunity proteins. The fusion sites in the hybrid proteins
      were positioned according to the three-dimensional structure of the soluble form
      of the colicin A pore-forming domain. The hydrophobic hairpin of colicin pore
      forming domains, buried in the core of the soluble structure, was the main
      determinant recognized by the integral immunity proteins. The immunity protein
      function may require helix-helix recognition within the lipid bilayer.

PMID- 1400194
TI  - Development of Thermus-Escherichia shuttle vectors and their use for expression
      of the Clostridium thermocellum celA gene in Thermus thermophilus.
AB  - We describe the self-selection of replication origins of undescribed cryptic
      plasmids from Thermus aquaticus Y-VII-51B (ATCC 25105) and a Thermus sp. strain
      (ATCC 27737) by random insertion of a thermostable kanamycin adenyltransferase
      cartridge. Once selected, these autonomous replication origins were cloned into
      the Escherichia coli vector pUC9 or pUC19. The bifunctional plasmids were
      analyzed for their sizes, relationships, and properties as shuttle vectors for
      Thermus-Escherichia cloning. Seven different vectors with diverse kanamycin
      resistance levels, stabilities, transformation efficiencies, and copy numbers
      were obtained. As a general rule, those from T. aquaticus (pLU1 to pLU4) were
      more stable than those from the Thermus sp. (pMY1 to pMY3). To probe their
      usefulness, we used one of the plasmids (pMY1) to clone in E. coli a modified
      form of the cellulase gene (celA) from Clostridium thermocellum in which the
      native signal peptide was replaced in vitro by that from the S-layer gene of T.
      thermophilus HB8. The hybrid product was expressed and exported by E. coli. When
      the gene was transferred by transformation into T. thermophilus, the cellulase
      protein was also expressed and secreted at 70 degrees C.

PMID- 1400196
TI  - Coordination of expression of Zymomonas mobilis glycolytic and fermentative
      enzymes: a simple hypothesis based on mRNA stability.
AB  - Although Zymomonas mobilis is prototrophic, glycolytic and fermentative enzymes
      (ethanologenic enzymes) constitute over half of the cytoplasmic protein. In this
      study, transcript stability, functional message pools, and the abundance of
      cytoplasmic products were compared for genes encoding eight of these essential
      enzymes. The transcripts of all were very stable, with half-lives ranging from 8
      to 18 min. This transcript stability is proposed as an important feature in Z.
      mobilis that may distinguish highly expressed genes for energy generation from
      biosynthetic genes, which are required at much lower levels. The evolution of
      multiple promoters to enhance transcription from single-copy genes, of structural
      features that alter translational efficiency, and of differences in protein
      turnover is hypothesized to serve a subordinate role in the regulation of Z.
      mobilis gene expression. Among the eight ethanologenic genes examined,
      differences in transcript stability were found to directly correlate with
      differences in functional message pools and cytoplasmic protein levels. These
      differences in transcript stability are hypothesized to have evolved as a primary
      mechanism to balance the levels of individual enzymes within the glycolytic and
      fermentative pathways.

PMID- 1400198
TI  - Generation of lipooligosaccharide mutants of Haemophilus influenzae type b.
AB  - We previously reported the analysis of recombinant plasmids from Haemophilus
      influenzae type b (Hib) that lead to modifications of Escherichia coli
      lipopolysaccharide (LPS) (Y. Abu Kwaik, R. E. McLaughlin, M. A. Apicella, and S.
      M. Spinola, Mol. Microbiol. 5:2475-2480, 1991). The modified LPS species are
      recognized by monoclonal antibodies (MAbs) 6E4 and 3F11. MAb 6E4 binds to a
      stable 2-keto-3-deoxyoctulosonic acid epitope, while MAb 3F11 binds to a Gal beta
      1-4GlcNac epitope that phase varies in Hib at a frequency of 2 to 5%. The
      internal EcoRI fragment containing most of the DNA required for LPS modification
      in E. coli was used as the target for transposon mutagenesis. Plasmids containing
      minitransposon m-Tn3(Cm) randomly inserted into the target fragment were
      transformed into the isogenic Hib strain, and transposon integration into the Hib
      chromosome was verified by colony hybridization. The lipooligosaccharides of 36
      transformants were phenotypically and antigenically characterized by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and reactivity with a variety
      of MAbs that recognize both stable and phase-varying lipooligosaccharide
      epitopes. The majority of the mutants had altered reactivity with MAb 6E4. With
      one exception, these mutants retained the ability to express phase-varying
      epitopes. Analysis of the transformants suggested that the 6E4 epitope was
      contained on an oligosaccharide chain separate from that of phase-varying
      epitopes and appeared to be assembled in at least three separate steps.

PMID- 1400199
TI  - Detection of growth sites in and protomer pools for the sheath of
      Methanospirillum hungatei GP1 by use of constituent organosulfur and immunogold
      labeling.
AB  - Methanospirillum hungatei GP1 integrated approximately 9% of cellular
      [35S]cysteine into its sheath. Autoradiography of sodium dodecyl sulfate
      polyacrylamide gels revealed that [35S]cysteine was confined to the proteins
      released by the sodium dodecyl sulfate-beta-mercaptoethanol-EDTA solubilization
      method (G. Southam and T. J. Beveridge, J. Bacteriol. 173:6213-6222, 1991) and
      was not present in the proteins released by treatment with phenol (G. Southam and
      T. J. Beveridge, J. Bacteriol. 174:935-946, 1992). Limited labeling of exposed
      sulfhydryl groups on hoops produced from sheath material suggested that most
      organosulfur groups occur within hoops and therefore help contribute to
      resilience. Electron microscopic autoradiography demonstrated that sheath growth,
      which is most active at the sites of cell division (spacer region), occurs
      through the de novo development of hoops. For growth to occur in the spacer
      region, sheath precursors must transverse several periodic envelope layers,
      including the cell wall (a single layer) and the various lamellae of the spacer
      plug (T. J. Beveridge, G. D. Sprott, and P. Whippey, J. Bacteriol. 173:130-140,
      1991).

PMID- 1400197
TI  - Rhodobacter sphaeroides rdxA, a homolog of Rhizobium meliloti fixG, encodes a
      membrane protein which may bind cytoplasmic [4Fe-4S] clusters.
AB  - In the photosynthetic bacterium Rhodobacter sphaeroides, a chromosomal gene,
      rdxA, which encodes a 52-kDa protein, was found to be homologous to fixG, the
      first gene of a Rhizobium meliloti nitrogen fixation operon on the pSym plasmid
      (D. Kahn, M. David, O. Domergue, M.-L. Daveran, J. Ghai, P. R. Hirsch, and J.
      Batut, J. Bacteriol. 171:929-939, 1989). The deduced amino acid sequences of RdxA
      and FixG are 53% identical and 73% similar; sequence analyses suggested that each
      has five transmembrane helices and a central region resembling bacterial-type
      ferredoxins. Translational fusion proteins with an alkaline phosphatase reporter
      group were expressed in both R. sphaeroides and Escherichia coli and were used to
      assess the membrane topology of RdxA. Its ferredoxinlike sequence, which may bind
      two [4Fe-4S] centers, was found to be cytoplasmically located. Genetic
      disruptions showed that rdxA is not essential for nitrogen fixation in R.
      sphaeroides. Immediately downstream of rdxA, an open reading frame (ORFT2) that
      encoded a 48-kDa protein was found. This DNA sequence was not homologous to any
      region of the R. meliloti fixG operon. The N-terminal sequence of the ORFT2 gene
      product resembled amino acid sequences found in members of the GntR family of
      regulatory proteins (D. J. Haydon and J. R. Guest, FEMS Microbiol. Lett. 79:291
      296, 1991). The rdxA gene was localized to the smaller of two R. sphaeroides
      chromosomes, upstream of and divergently transcribed from hemT, which encodes one
      of two 5-aminolevulinate synthase isozymes. The rdxA and hemT genes may share a
      transcriptional regulatory region. Southern hybridization analysis demonstrated
      the presence of an rdxA homolog on the R. sphaeroides large chromosome. The
      functions of this homolog, like those of rdxA, remain to be determined, but roles
      in oxidation-reduction processes are likely.

PMID- 1400200
TI  - Identification of an operon involved in sulfolipid biosynthesis in Rhodobacter
      sphaeroides.
AB  - Two new mutants of Rhodobacter sphaeroides deficient in sulfolipid accumulation
      were isolated by directly screening mutagenized cell lines for polar lipid
      composition by thin-layer chromatography of lipid extracts. A genomic clone which
      complemented the mutations in these two lines, but not the previously described
      sulfolipid-deficient sqdA mutant, was identified. Sequence analysis of the
      relevant region of the clone revealed three, in tandem open reading frames,
      designated sqdB, ORF2, and sqdC. One of the mutants was complemented by the sqdB
      gene, and the other was complemented by the sqdC gene. Insertional inactivation
      of sqdB also inactivated sqdC, indicating that sqdB and sqdC are cotranscribed.
      The N-terminal region of the 46-kDa putative protein encoded by the sqdB gene
      showed slight homology to UDP-glucose epimerase from various organisms. The 30
      kDa putative protein encoded by ORF2 showed very striking homology to rabbit
      muscle glycogenin, a UDP-glucose utilizing, autoglycosylating
      glycosyltransferase. The 26-kDa putative protein encoded by the sqdC gene was not
      homologous to any protein of known function.

PMID- 1400201
TI  - Alterations in the hydrophilic segment of the maltose-binding protein (MBP)
      signal peptide that affect either export or translation of MBP.
AB  - Mutations that reduce the net positive charge within the hydrophilic segments of
      the signal peptides of several prokaryotic exported proteins can result in a
      reduction in the rate of protein export, as well as a reduction in protein
      synthesis (M. N. Hall, J. Gabay, and M. Shwartz, EMBO J. 2:15-19, 1983; S.
      Inouye, X. Soberon, T. Franceschini, K. Nakamura, K. Itakura, and M. Inouye,
      Proc. Natl. Acad. Sci. USA 79:3438-3441, 1982; J. W. Puziss, J. D. Fikes, and P.
      J. Bassford, Jr., J. Bacteriol. 171:2302-2311, 1989). This result has been
      interpreted as evidence that the hydrophilic segment is part of a mechanism that
      obligatorily couples translation to protein export. We have investigated the role
      of the hydrophilic segment of the Escherichia coli maltose-binding protein (MBP)
      signal peptide in the export and synthesis of MBP. Deletion of the entire
      hydrophilic segment from the MBP signal peptide resulted in a defect in MBP
      export, as well as a dramatic reduction in total MBP synthesis. Suppressor
      mutations that lie upstream of the malE coding region were isolated. These
      mutations do not affect MBP export but instead were shown to partially restore
      MBP synthesis by increasing the efficiency of MBP translational initiation. In
      addition, analysis of a series of substitution mutations in the second codon of
      certain malE alleles demonstrated that MBP export and synthesis can be
      independently affected by mutations in the hydrophilic segment. Finally, analysis
      of alterations in the hydrophilic segment of the ribose-binding protein signal
      peptide fused to the mature moiety of the MBP has revealed that the role of the
      hydrophilic segment in the export process can be functionally separated from any
      role in translation. Taken together, these results strongly suggest that the
      hydrophilic segment of the MBP signal peptide is not involved in a mechanism that
      couples MBP translation to export and argue against the presence of a mechanism
      that obligatorily couples translation to protein export in Escherichia coli.

PMID- 1400202
TI  - Identification of a B subunit gene promoter in the Shiga toxin operon of Shigella
      dysenteriae 1.
AB  - The Shiga toxin operon (stx) is composed of A and B subunit genes which are
      transcribed as a bicistronic mRNA from a promoter which lies 5' to the stxA gene.
      Northern (RNA) blot and primer extension analyses revealed the existence of a
      second stxB gene transcript. Recombinant plasmids which carried the stxB gene
      without the stx operon promoter and with the influence of a vector promoter
      abrogated produced STX B polypeptides, suggesting that the stxB gene mRNA was
      transcribed from an independent promoter and was not produced by
      endoribonucleotic processing of the bicistronic mRNA. Examination of the DNA
      sequences 5' to the stxB gene transcription initiation site which were carried by
      the recombinant plasmids revealed a region with high homology to the consensus
      for Escherichia coli promoters. Deletion and mutation of this region affected
      StxB and holotoxin production, establishing its role in the regulation of the
      stxB gene. Comparison of the promoters by using a transcription analysis vector
      revealed that the stxB gene promoter differed from the stx operon promoter in
      that was approximately sixfold less efficient and was not repressed by iron.
      Identification of a second promoter in the stx operon indicates that independent
      transcription of the stxB gene may regulate overproduction of the STX B
      polypeptides and may contribute to the 1A:5B subunit stoichiometry of the
      holotoxin.

PMID- 1400203
TI  - Reevaluation of envelope profiles and cytoplasmic ultrastructure of mycobacteria
      processed by conventional embedding and freeze-substitution protocols.
AB  - The cell envelope architectures and cytoplasmic structures of Mycobacterium aurum
      CIPT 1210005, M. fortuitum, M. phlei 425, and M. thermoresistible ATCC 19527 were
      compared by conventional embedding and freeze-substitution methods. To ascertain
      the integrity of cells during each stage of the processing regimens, [1
      14C]acetate was incorporated into the mycolic acids of mycobacterial walls, and
      the extraction of labeled mycolic acids was monitored by liquid scintillation
      counting. Radiolabeled mycolic acids were extracted by both processing methods;
      however, freeze-substitution resulted in the extraction of markedly less
      radiolabel. During conventional processing of cells, most of the radiolabel was
      extracted during the dehydration stage, whereas postsubstitution washes in
      acetone yielded the greatest loss of radiolabel during freeze-substitution.
      Conventional embedding frequently produced cells with condensed fibrous nucleoids
      and occasional mesosomes. Their cell walls were relatively thick (approximately
      25 nm) but lacked substance. Freeze-substituted cells appeared more robust, with
      well-dispersed nucleoids and ribosomes. The walls of all species were much
      thinner than those of their conventionally processed counterparts, but these
      stained well, which was an indication of more wall substance; the fabric of these
      walls, in particular the plasma membrane, appeared highly condensed and tightly
      apposed to the peptidoglycan. Some species possessed a thick, irregular outer
      layer that was readily visualized in the absence of exogenous stabilizing agents
      by freeze-substitution. Since freeze-substituted mycobacteria retained a greater
      percentage of mycolic acids in their walls, and probably other labile wall and
      cytoplasmic constituents, we believe that freeze-substitution provides a more
      accurate image of structural organization in mycobacteria than that achieved by
      conventional procedures.

PMID- 1400205
TI  - The S-layer of Caulobacter crescentus: three-dimensional image reconstruction and
      structure analysis by electron microscopy.
AB  - The regular surface protein structure (S-layer) of Caulobacter crescentus was
      analyzed by electron microscopy and three-dimensional image reconstruction to a
      resolution of 2 nm. Projections showed that the S-layer is an array of ring
      structures, each composed of six subunits that are arranged on a lattice with p6
      symmetry. Three-dimensional reconstructions showed that the ring subunits were
      approximately rod-shaped structures and were perpendicular to the plane of the
      array, with a linker arm emanating from approximately the middle of the rod,
      accounting for the connections between the rings. The calculated subunit mass was
      ca. 100 kDa, very close to the size of RsaA (the protein known to be at least the
      predominant species in the S-layer) predicted from the DNA sequence of the rsaA
      gene. The core region of the rings creates an open pore 2.5 to 3.5 nm in
      diameter. The size of the gaps between the neighboring unit cells is in the same
      range, suggesting a uniform porosity predicted to exclude molecules larger than
      ca. 17 kDa. Attempts to remove membrane material from S-layer preparations with
      detergents revealed that the structure spontaneously rearranged into a mirror
      image double layer. Negative-stain and thin-section electron microscopy
      examination of colonies of C. crescentus strains with a mutation in a surface
      molecule involved in the attachment of the S-layer showed that shed RsaA protein
      organized into large sheets. The sheets in turn organized into stacks that tended
      to accumulate near the upper surface of the colony. Image reconstruction
      indicated that these sheets were also precise mirror-image double layers, and
      thickness measurements obtained from thin sections were consistent with this
      finding. The sheets were absent when these mutant strains were grown without
      calcium, supporting other data that calcium is involved in attachment of the S
      layer to a surface molecule and perhaps in subunit-subunit interactions. We
      propose that when the membrane is removed from S-layer fragments by detergents or
      the attachment-related surface molecule is absent, the attachment sites of the S
      layer align precisely to form a double layer via a calcium interaction.

PMID- 1400204
TI  - Complete nucleotide sequence of tbuD, the gene encoding phenol/cresol hydroxylase
      from Pseudomonas pickettii PKO1, and functional analysis of the encoded enzyme.
AB  - The gene (tbuD) encoding phenol hydroxylase, the enzyme that converts cresols or
      phenol to the corresponding catechols, has been cloned from Pseudomonas pickettii
      PKO1 as a 26.5-kbp BamHI-cleaved DNA fragment, designated pRO1957, which allowed
      the heterogenetic recipient Pseudomonas aeruginosa PAO1c to grow on phenol as the
      sole source of carbon. Two subclones of pRO1957 carried in trans have shown
      phenol hydroxylase activity in cell extracts of P. aeruginosa. The nucleotide
      sequence was determined for one of these subclones, a 3.1-kbp HindIII fragment,
      and an open reading frame that would encode a peptide of 73 kDa was found. The
      size of this deduced peptide is consistent with the size of a novel peptide that
      had been detected in extracts of phenol-induced cells of P. aeruginosa carrying
      pRO1959, a partial HindIII deletion subclone of pRO1957. Phenol hydroxylase
      purified from phenol-plus-Casamino Acid-grown cells of P. aeruginosa carrying
      pRO1959 has an absorbance spectrum characteristic of a simple flavoprotein;
      moreover, the enzyme exhibits a broad substrate range, accommodating phenol and
      the three isomers of cresol equally well. Sequence comparisons revealed little
      overall homology with other flavoprotein hydroxylases, supporting the novelty of
      this enzyme, although three conserved domains were apparent.

PMID- 1400206
TI  - Sequence and characterization of the bacteriophage T4 comC alpha gene product, a
      possible transcription antitermination factor.
AB  - We have sequenced a 1,340-bp region of the bacteriophage T4 DNA spanning the comC
      alpha gene, a gene which has been implicated in transcription antitermination. We
      show that comC alpha, identified unambiguously by sequencing several missense and
      nonsense mutations within the gene, codes for an acidic polypeptide of 141
      residues, with a predicted molecular weight of 16,680. We have identified its
      product on one- and two-dimensional gel systems and found that it migrates
      abnormally as a protein with a molecular weight of 22,000. One of the missense
      mutations (comC alpha 803) is a glycine-to-arginine change, and the resulting
      protein exhibits a substantially faster electrophoretic mobility. The ComC alpha
      protein appears immediately after infection. Its rate of synthesis is maximum
      around 2 to 3 min postinfection (at 37 degrees C) and then starts to decrease
      slowly. Some residual biosynthesis is still detectable during the late period of
      phage development.

PMID- 1400207
TI  - Molecular characterization of the Zymomonas mobilis enolase (eno) gene.
AB  - The Zymomonas mobilis gene encoding enolase was cloned by genetic complementation
      of an Escherichia coli eno mutant. An enzyme assay and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis confirmed the overexpression of enolase in E.
      coli clones carrying the Z. mobilis eno gene. The eno gene is present in a single
      copy of the Z. mobilis genome. Nucleotide sequence analysis of the eno region
      revealed an open reading frame of 1,293 bp that encodes a protein of 428 amino
      acids with a predicted molecular weight of 45,813. Comparison of the sequence of
      Z. mobilis enolase with primary amino acid sequences for other enolases indicates
      that the enzyme is highly conserved. Unlike all of the previously studied
      glycolytic genes from Z. mobilis that possess canonical ribosome binding sites,
      the eno gene is preceded by a modest Shine-Dalgarno sequence. The transcription
      initiation site was mapped by primer extension and found to be located within a
      115-bp sequence that is 55.7% identical to a highly conserved consensus sequence
      found within the regulatory regions of highly expressed Z. mobilis genes.
      Northern RNA blot analysis revealed that eno is encoded on a 1.45-kb transcript.
      The half-life of the eno mRNA was determined to be 17.7 +/- 1.7 min, indicating
      that it is unusually stable. The abundance of the eno message is proposed to
      account for enolase being the most prevalent protein in Z. mobilis.

PMID- 1400208
TI  - Tryptophan biosynthesis genes in Lactococcus lactis subsp. lactis.
AB  - The Lactococcus lactis chromosomal region containing the seven structural genes
      required for tryptophan biosynthesis was characterized by cloning and sequencing.
      All of the trp genes were identified by the homology of their products with known
      Trp proteins from other organisms. The identification was confirmed for five
      genes by their ability to complement trp mutations in Escherichia coli. The seven
      structural genes are present in the order trpEGDCFBA and span a 7,968-bp segment.
      Each gene is preceded by a putative ribosome binding site complementary to the 3'
      end of the L. lactis 16S rRNA. Three pairs of genes (trpG-trpD, trpC-trpF, and
      trpB-trpA) overlap, and there is intercistronic spacing of 124, 46, and 585 bp
      between the trpE-trpG, trpD-trpC, and trpF-trpB gene pairs, respectively. No gene
      fusion was found. Upstream of the trp genes, a 457-bp noncoding DNA segment
      contains several regions fitting the consensus for gram-positive promoters and
      one region strongly resembling a transcription terminator. However, it seems
      unlikely that an attenuation mechanism similar to the one found in E. coli
      regulates tryptophan biosynthesis in L. lactis, since no potential leader peptide
      was detected. We propose that a mechanisms resembling that described in Bacillus
      spp. can regulate trp genes expression in L. lactis.

PMID- 1400209
TI  - Histidine biosynthesis genes in Lactococcus lactis subsp. lactis.
AB  - The genes of Lactococcus lactis subsp. lactis involved in histidine biosynthesis
      were cloned and characterized by complementation of Escherichia coli and Bacillus
      subtilis mutants and DNA sequencing. Complementation of E. coli hisA, hisB, hisC,
      hisD, hisF, hisG, and hisIE genes and the B. subtilis hisH gene (the E. coli hisC
      equivalent) allowed localization of the corresponding lactococcal genes.
      Nucleotide sequence analysis of the 11.5-kb lactococcal region revealed 14 open
      reading frames (ORFs), 12 of which might form an operon. The putative operon
      includes eight ORFs which encode proteins homologous to enzymes involved in
      histidine biosynthesis. The operon also contains (i) an ORF encoding a protein
      homologous to the histidyl-tRNA synthetases but lacking a motif implicated in
      synthetase activity, which suggests that it has a role different from tRNA
      aminoacylation, and (ii) an ORF encoding a protein that is homologous to the 3'
      aminoglycoside phosphotransferases but does not confer antibiotic resistance. The
      remaining ORFs specify products which have no homology with proteins in the EMBL
      and GenBank data bases.

PMID- 1400210
TI  - Branched-chain amino acid biosynthesis genes in Lactococcus lactis subsp. lactis.
AB  - The genes for biosynthesis of the branched-chain amino acids leucine, isoleucine,
      and valine in Lactococcus lactis subsp. lactis NCDO2118 were characterized by
      cloning, complementation in Escherichia coli and Bacillus subtilis, and
      nucleotide sequence analysis. Nine structural genes are clustered on a 12-kb DNA
      fragment in the order leuABCD ilvDBNCA. Upstream of these genes, the nucleotide
      sequence suggests the existence of regulation by transcriptional attenuation.
      Between the leuD and ilvD genes is an unexpected gene, encoding a protein which
      belongs to the ATP-binding cassette protein superfamily.

PMID- 1400211
TI  - Purification and properties of an Arthrobacter oxydans P52 carbamate hydrolase
      specific for the herbicide phenmedipham and nucleotide sequence of the
      corresponding gene.
AB  - Arthrobacter oxydans P52 isolated from soil samples was found to degrade the
      phenylcarbamate herbicides phenmedipham and desmedipham cometabolically by
      hydrolyzing their central carbamate linkages. The phenylcarbamate hydrolase
      (phenmedipham hydrolase) responsible for the degradative reaction was purified to
      homogeneity. The enzyme was shown to be a monomer with a molecular weight of
      55,000. A 41-kb wild-type plasmid (pHP52) was identified in A. oxydans P52, but
      not in a derivative of this strain that had spontaneously lost the ability to
      hydrolyze phenylcarbamates, indicating that the gene for phenylcarbamate
      degradation (pcd) is plasmid encoded. Determination of two partial amino acid
      sequences allowed the localization of the coding sequence of the pcd gene on a
      3.3-kb PstI restriction fragment within pHP52 DNA by hybridization with synthetic
      oligonucleotides. The phenylcarbamate hydrolase was functionally expressed in
      Escherichia coli under control of the lacZ promoter after the 3.3-kb PstI
      fragment was subcloned into the vector pUC19. A stretch of 1,864 bases within the
      cloned Pst fragment was sequenced. Sequence analysis revealed an open reading
      frame of 1,479 bases containing the amino acid partial sequences determined for
      the purified enzyme. Sequence comparisons revealed significant homology between
      the pcd gene product and the amino acid sequences of esterases of eukaryotic
      origin. Subsequently, it was demonstrated that the esterase substrate p
      nitrophenylbutyrate is hydrolyzed by phenmedipham hydrolase.

PMID- 1400212
TI  - Structural characterization of ordered arrays of sn-glycerol-3-phosphate
      acyltransferase from Escherichia coli.
AB  - Overproduction of the sn-glycerol-3-phosphate acyltransferase in Escherichia coli
      leads to incorporation of this integral membrane protein into ordered tubular
      arrays within the cell. Freeze-fracture-etch shadowing was performed on
      suspensions of partially purified tubules and whole bacteria. This procedure
      revealed the presence of ridges and grooves defining a set of long-pitch left
      handed helical ridges. The long-pitch helices represented chains of
      acyltransferase dimers. Tubules observed within the cell were often closely
      packed, with an apparent alignment of grooves and ridges in adjacent tubules.
      Fracture planes passing through the tubules indicated the presence of a bilayer
      structure, with some portion of the enzyme being associated with the membrane.
      The major portion of the enzyme extended from the hydrophilic surface, forming a
      large globular structure that, in favorable views, displayed a central cavity
      facing the cytoplasm. Computer analysis of shadowed tubules revealed that the
      left-handed helices were six stranded, with a pitch of 1,050 A (105.0 nm) and a
      spacing of 75 A (7.5 nm) between acyltransferase dimers along the chains.
      Analysis of the predicted secondary structure failed to reveal obvious
      transmembrane segments, suggesting that very little of the protein was inserted
      into the bilayer.

PMID- 1400213
TI  - Electrotransformation of Thiobacillus ferrooxidans with plasmids containing a mer
      determinant.
AB  - The mer operon from a strain of Thiobacillus ferrooxidans (C. Inoue, K. Sugawara,
      and T. Kusano, Mol. Microbiol. 5:2707-2718, 1991) consists of the regulatory gene
      merR and an operator-promoter region followed by merC and merA structural genes
      and differs from other known gram-negative mer operons. We have constructed four
      potential shuttle plasmids composed of a T. ferrooxidans-borne cryptic plasmid, a
      pUC18 plasmid, and the above-mentioned mer determinant as a selectable marker.
      Mercury ion-sensitive T. ferrooxidans strains were electroporated with
      constructed plasmids, and one strain, Y4-3 (of 30 independent strains tested),
      was found to have a transformation efficiency of 120 to 200 mercury-resistant
      colonies per microgram of plasmid DNA. This recipient strain was confirmed to be
      T. ferrooxidans by physiological, morphological, and chemotaxonomical data. The
      transformants carried a plasmid with no physical rearrangements through 25
      passages under no selective pressure. Cell extracts showed mercury ion-dependent
      NADPH oxidation activity.

PMID- 1400214
TI  - AlgR-binding sites within the algD promoter make up a set of inverted repeats
      separated by a large intervening segment of DNA.
AB  - Activation of algD by AlgR is essential for mucoidy, a virulence factor expressed
      by Pseudomonas aeruginosa in cystic fibrosis. Two AlgR-binding sites, RB1 and
      RB2, located far upstream from the algD mRNA start site, are essential for the
      high-level activity of algD. However, the removal of RB1 and RB2 does not
      completely abolish inducibility of algD in response to environmental signals. In
      this work, a third binding site for AlgR, termed RB3, near the algD mRNA start
      site was characterized. Deletion of RB3 abrogated both the AlgR-binding ability
      and the residual inducibility of the algD promoter. DNase I footprinting analysis
      of RB3 resulted in a protection pattern spanning nucleotides -50 to -30. Eight of
      10 residues encompassing a continuous region of protection within RB3 (positions 
      45 to -36) matched in the inverted orientation the conserved core sequence
      (ACCGTTCGTC) of RB1 and RB2. Quantitative binding measurements of AlgR
      association with RB1, RB2, and RB3 indicated that AlgR had significantly lower
      affinity for RB3 than for RB1 and RB2, with differences in the free energy of
      binding of 1.05 and 0.93 kcal/mol (4.39 and 3.89 kJ/mmol), respectively. Altering
      the core of RB2 to match the core of RB3 significantly reduced AlgR binding.
      Conversely, changing the core of RB3 to perfectly match the core of RB2 (mutant
      site termed RB3*) improved AlgR binding, approximating the affinity of RB2. RB3*,
      in the absence of the far upstream sites, showed an increase in activity,
      approaching the levels observed with the full-size algD promoter. Changing 4
      nucleotides in two different combinations within the core of RB3 abolished the
      binding of AlgR to this site and resulted in a significant reduction of promoter
      activity in the presence of the far upstream sites. Thus, (i) the core sequence
      is essential for AlgR binding; (ii) the three binding sites, RB1, RB2, and RB3,
      are organized as an uneven palindrome with symmetrical sequences separated by 341
      and 417 bp; and (iii) all three sites participate in algD activation.

PMID- 1400215
TI  - Escherichia coli produces a cytoplasmic alpha-amylase, AmyA.
AB  - In the gap between two closely linked flagellar gene clusters on the Escherichia
      coli and Salmonella typhimurium chromosomes (at about 42 to 43 min on the E. coli
      map), we found an open reading frame whose sequence suggested that it encoded an
      alpha-amylase; the deduced amino acid sequences in the two species were 87%
      identical. The strongest similarities to other alpha-amylases were to the
      excreted liquefying alpha-amylases of bacilli, with > 40% amino acid identity;
      the N-terminal sequence of the mature bacillar protein (after signal peptide
      cleavage) aligned with the N-terminal sequence of the E. coli or S. typhimurium
      protein (without assuming signal peptide cleavage). Minicell experiments
      identified the product of the E. coli gene as a 56-kDa protein, in agreement with
      the size predicted from the sequence. The protein was retained by spheroplasts
      rather than being released with the periplasmic fraction; cells transformed with
      plasmids containing the gene did not digest extracellular starch unless they were
      lysed; and the protein, when overproduced, was found in the soluble fraction. We
      conclude that the protein is cytoplasmic, as predicted by its sequence. The
      purified protein rapidly digested amylose, starch, amylopectin, and maltodextrins
      of size G6 or larger; it also digested glycogen, but much more slowly. It was
      specific for the alpha-anomeric linkage, being unable to digest cellulose. The
      principal products of starch digestion included maltotriose and maltotetraose as
      well as maltose, verifying that the protein was an alpha-amylase rather than a
      beta-amylase. The newly discovered gene has been named amyA. The natural
      physiological role of the AmyA protein is not yet evident.

PMID- 1400216
TI  - Role of the origin of transfer in termination of strand transfer during bacterial
      conjugation.
AB  - Conjugal transfer of the broad-host-range plasmid R1162 is initiated and
      terminated at the nic site within the 38-bp origin of transfer (oriT).
      Termination involves ligation of the transferred single strand by the plasmid
      encoded MobA protein. Several different assays were used to identify the oriT DNA
      required for termination. For plasmids containing two oriTs, with transfer
      initiated at one and terminated at the other, the inverted repeat within oriT is
      important for termination. Deletion of the outer arm reduces the termination
      frequency; those terminations that do occur probably depend upon nicking at this
      oriT prior to transfer. The locations of second-site suppressor mutations
      indicate that base pairing between the arms of the inverted repeat is important
      for termination. In vitro, the inverted repeat is not required for specific
      cleavage of single-stranded DNA at nic, but competition experiments indicate that
      oriTs with the inverted repeat are preferentially cleaved. We propose that the
      function of the oriT inverted repeat is to trap the plasmid-encoded MobA protein
      at the end of a round of strand transfer, thus ensuring that the protein is
      available for the ligation step.

PMID- 1400218
TI  - Saccharomyces cerevisiae has distinct adaptive responses to both hydrogen
      peroxide and menadione.
AB  - Treatment of Saccharomyces cerevisiae cells with low concentrations of either
      hydrogen peroxide or menadione (a superoxide-generating agent) induces adaptive
      responses which protect cells from the lethal effects of subsequent challenge
      with higher concentrations of these oxidants. Pretreatment with menadione is
      protective against cell killing by hydrogen peroxide; however, pretreatment with
      hydrogen peroxide is unable to protect cells from subsequent challenge with
      menadione. This suggests that the adaptive responses to these two different
      oxidants may be distinct.

PMID- 1400217
TI  - Mutational analysis of essential IncP alpha plasmid transfer genes traF and traG
      and involvement of traF in phage sensitivity.
AB  - Although the broad-host-range IncP plasmids can vegetatively replicate in diverse
      gram-negative bacteria, the development of shuttle vector systems has established
      that the host range for IncP plasmid conjugative transfer is greater than the
      range of bacteria that sustain IncP replicons. Towards understanding IncP plasmid
      conjugation and the connection between IncP conjugation and Agrobacterium
      tumefaciens T-DNA transfer to plants, two sets of mutants were generated in the
      larger transfer region (Tra1) of the IncP alpha plasmid RK2. Mutagenesis
      strategies were chosen to minimize transcriptional polar effects. Mutant Tra1
      clones were mapped, sequenced, and processed to reconstruct 49.5-kb Tra2
      containing plasmid derivatives in order to assay for transfer activity and IncP
      plasmid-specific phage sensitivity. Focusing on the activities of the gene
      products of traF and traG in Escherichia coli, we found that mutations in traF
      abolished transfer activity and rendered the host cells phage resistant and
      mutations in traG abolished transfer activity but had no effect on phage
      sensitivity. Complementation of these mutant derivatives with corresponding trans
      acting clones carrying traF or traG restored transfer activity and, in the case
      of the traF mutant, the phage sensitivity of the host cell. We conclude that in
      E. coli, both TraF and TraG are essential for IncP plasmid transfer and that TraF
      is necessary (but not sufficient) for donor-specific phage sensitivity, and
      sequencing data suggest that both TraF and TraG are membrane spanning.

PMID- 1400219
TI  - The presence of only one of five exoribonucleases is sufficient to support the
      growth of Escherichia coli.
AB  - Escherichia coli contains multiple exoribonucleases. Strains lacking the
      exoribonucleases RNase II, D, BN, T, and PH are inviable. The introduction of a
      chromosomal, wild-type copy of the gene for any one of these enzymes is
      sufficient to allow cell growth, with the enzymes being in the following order of
      effectiveness: RNase T > RNase PH > RNase D > RNase II > RNase BN. The data
      indicate that these five exoribonucleases functionally overlap in vivo and that
      any one of them can take over the functions of all the others, although with
      various efficiencies.

PMID- 1400220
TI  - Biosynthetic pathways of the osmolytes N epsilon-acetyl-beta-lysine, beta
      glutamine, and betaine in Methanohalophilus strain FDF1 suggested by nuclear
      magnetic resonance analyses.
AB  - Methanohalophilus strain FDF1 synthesizes beta-glutamine, betaine, and N epsilon
      acetyl-beta-lysine as osmoprotective agents when the cells are grown in high
      external concentrations of NaCl. Nuclear magnetic resonance spectroscopic
      analyses of 13CH3OH-12CO2 label incorporation by the cells provide information on
      the biosynthetic pathways of these organic osmolytes. The labeling studies
      indicate that Methanohalophilus strain FDF1 produces glutamate and beta-glutamine
      via a partial oxidative Krebs pathway. 13C labeling of betaine is consistent with
      methylation of glycine generated from serine (via serine
      hydroxymethyltransferase). The labeling pattern for N epsilon-acetyl-beta-lysine
      is consistent with the synthesis of its precursor alpha-lysine occurring by the
      diaminopimelate pathway in these cells.

PMID- 1400221
TI  - Determination of the sequence of spaE and identification of a promoter in the
      subtilin (spa) operon in Bacillus subtilis.
AB  - An 851-residue open reading frame (ORF) called SpaE has been discovered in the
      subtilin (spa) operon. Interruption of this ORF with a chloramphenicol
      acetyltransferase gene destroys the ability of Bacillus subtilis LH45 delta c (a
      derivative of B. subtilis 168) to produce subtilin, which is an antimicrobial
      peptide belonging to the class of ribosomally synthesized peptide antibiotics
      called lantibiotics. SpaE shows strong homology to NisB, which is in the nisin
      (nis) operon in Lactococcus lactis ATCC 11454. Despite the strong sequence
      homology between SpaE and NisB, the spaE and nisB genes occupy very different
      locations in their respective operons, indicating that they have been evolving
      separately for a long time. Primer extension analysis was employed to identify a
      promoter upstream from the spaE gene, which appears to define the 5' end of the
      spa operon, which contains four other ORFs (Y. J. Chung, M. T. Steen, and J. N.
      Hansen, J. Bacteriol. 174:1417-1422, 1992).

PMID- 1400222
TI  - Site-specific recombination of the circular 2 microns-like plasmid pKD1 requires
      integrity of the recombinase gene A and of the partitioning genes B and C.
AB  - In the circular plasmid pKD1, which stably replicates in Kluyveromyces lactis,
      the three open reading frames encode a site-specific recombinase (gene A) and two
      proteins involved in mitotic stability (genes B and C). A recombination analysis
      of plasmids in which gene B or C is inactivated reveals that unlike the 2 microns
      plasmid of Saccharomyces cerevisiae, these genes are also required for the site
      specificity of plasmid recombination.

PMID- 1400223
TI  - How the phage lambda N gene product suppresses transcription termination:
      communication of RNA polymerase with regulatory proteins mediated by signals in
      nascent RNA.

PMID- 1400225
TI  - The divIVB region of the Bacillus subtilis chromosome encodes homologs of
      Escherichia coli septum placement (minCD) and cell shape (mreBCD) determinants.
AB  - Mutation of the divIVB locus in Bacillus subtilis causes frequent misplacement of
      the division septum, resulting in circular minicells, short rods, and filaments
      of various sizes. The divIVB1 mutant allele maps to a region of the chromosome
      also known to encode sporulation (spo0B, spoIVF, spoIIB) and cell shape (rodB)
      determinants. This study reports the cloning and sequence analysis of 4.4 kb of
      the B. subtilis chromosome encompassing the divIVB locus. This region contains
      five open reading frames (ORFs) arranged in two functionally distinct gene
      clusters (mre and min) and transcribed colinearly with the direction of
      replication. Although sequence analysis reveals potential promoters preceding
      each gene cluster, studies with integrational plasmids suggest that all five ORFs
      are part of a single transcription unit. The first gene cluster contains three
      ORFs (mreBCD) homologous to the mre genes of Escherichia coli. We show that rodB1
      is allelic to mreD and identify the rodB1 mutation. The second gene cluster
      contains two ORFs (minCD) homologous to minC and minD of E. coli but lacks a minE
      homolog. We show that divIVB1 is allelic to minD and identify two mutations in
      the divIVB1 allele. Insertional inactivation of either minC or minD or the
      presence of the divIVB region on plasmids produces a severe minicell phenotype in
      wild-type cells. Moreover, E. coli cells carrying the divIVB region on a low-copy
      number plasmid produce minicells, suggesting that a product of this locus may
      retain some function across species boundaries.

PMID- 1400224
TI  - Identification of Bacillus subtilis genes for septum placement and shape
      determination.
AB  - The Bacillus subtilis divIVB1 mutation causes aberrant positioning of the septum
      during cell division, resulting in the formation of small, anucleate cells known
      as minicells. We report the cloning of the wild-type allele of divIVB1 and show
      that the mutation lies within a stretch of DNA containing two open reading frames
      whose predicted products are in part homologous to the products of the
      Escherichia coli minicell genes minC and minD. Just upstream of minC and minD,
      and in the same orientation, are three genes whose products are homologous to the
      products of the E. coli shape-determining genes mreB, mreC, and mreD. The B.
      subtilis mreB, mreC, and mreD genes are the site of a conditional mutation
      (rodB1) that causes the production of aberrantly shaped cells under restrictive
      conditions. Northern (RNA) hybridization experiments and disruption experiments
      based on the use of integrational plasmids indicate that the mre and min genes
      constitute a five-cistron operon. The possible involvement of min gene products
      in the switch from medial to polar placement of the septum during sporulation is
      discussed.

PMID- 1400226
TI  - Characterization of the Bacillus subtilis rpsD regulatory target site.
AB  - The Bacillus subtilis rpsD gene, which encodes ribosomal protein S4, is subject
      to autogenous regulation. Repression of rpsD expression by excess S4 protein was
      previously shown to be affected by mutations in the leader region of the gene. A
      large number of deletion and point mutations in the leader region were generated,
      and their effect on repression by S4 in vivo was tested. These studies indicated
      that the required region was within positions +30 to +190 relative to the
      transcription start point. Replacement of the rpsD promoter with a lac promoter
      derivative which is expressed in B. subtilis had no effect, indicating that
      repression by S4 occurs at a level subsequent to transcription initiation. The
      rpsD leader region was isolated from several Bacillus species. Members of the B.
      subtilis group, as defined by analysis of 16S rRNA sequence, contained a leader
      region target site very closely related in structure to that of B. subtilis,
      despite considerable primary sequence variation; the B. brevis rpsD leader
      contained some but not all of the structural features found in the regulatory
      target sites of the other Bacillus species. Very little similarity to the
      Escherichia coli alpha operon S4 target site was found at either the primary
      sequence or the secondary-structure level. Mutagenic and phylogenetic data
      indicate that the secondary structure of the leader region regulatory target site
      contains two large stem-loop domains. The first of these helices has a side loop
      which is essential for autoregulation, is highly conserved among Bacillus rpsD
      genes, and is similar to a region of 16S rRNA important in S4 binding.

PMID- 1400227
TI  - A heterologous membrane protein domain fused to the C-terminal ATP-binding domain
      of HlyB can export Escherichia coli hemolysin.
AB  - The hydrophobic-rich NH2-terminal 34 amino acids of a tetracycline resistance
      determinant (TetC) were fused to the COOH-terminal 240 amino acids of the
      hemolysin transporter, HlyB, which contains a putative ATP-binding domain. This
      hybrid protein replaced the NH2-terminal 467-amino-acid portion of HlyB and could
      still export the Escherichia coli hemolysin (HlyA). Export by the hybrid protein
      was approximately 10% as efficient as transport by HlyB. Extracellular secretion
      of HlyA by the TetC-HlyB hybrid required HlyD and TolC. The extracellular and
      periplasmic levels of beta-galactosidase and beta-lactamase in strains that
      produced the hybrid were similar to the levels in controls. Thus, HlyA transport
      was specific and did not appear to be due to leakage of cytoplasmic contents
      alone. Antibodies raised against the COOH terminus of HlyB reacted with the
      hybrid protein, as well as HlyB. HlyB was associated with membrane fractions,
      while the hybrid protein was found mainly in soluble extracts. Cellular
      fractionation studies were performed to determine whether transport by the hybrid
      occurred simultaneously across both membranes like wild-type HlyA secretion.
      However, we found that HlyA was present in the periplasm of strains that
      expressed the TetC-HlyB hybrid. HlyA remained in the periplasm unless the hlyD
      and tolC gene products were present in addition to the hybrid.

PMID- 1400228
TI  - Molecular cloning of cDNA and analysis of protein secondary structure of Candida
      albicans enolase, an abundant, immunodominant glycolytic enzyme.
AB  - We isolated and sequenced a clone for Candida albicans enolase from a C. albicans
      cDNA library by using molecular genetic techniques. The 1.4-kbp cDNA encoded one
      long open reading frame of 440 amino acids which was 87 and 75% similar to
      predicted enolases of Saccharomyces cerevisiae and enolases from other organisms,
      respectively. The cDNA included the entire coding region and predicted a protein
      of molecular weight 47,178. The codon usage was highly biased and similar to that
      found for the highly expressed EF-1 alpha proteins of C. albicans. Northern (RNA)
      blot analysis showed that the enolase cDNA hybridized to an abundant C. albicans
      mRNA of 1.5 kb present in both yeast and hyphal growth forms. The polypeptide
      product of the cloned cDNA, which was purified as a recombinant protein fused to
      glutathione S-transferase, had enolase enzymatic activity and inhibited
      radioimmunoprecipitation of a single C. albicans protein of molecular weight
      47,000. Analysis of the predicted C. albicans enolase showed strong conservation
      in regions of alpha helices, beta sheets, and beta turns, as determined by
      comparison with the crystal structure of apo-enolase A of S. cerevisiae. The lack
      of cysteine residues and a two-amino-acid insertion in the main domain
      differentiated C. albicans enolase from S. cerevisiae enolase. Immunofluorescence
      of whole C. albicans cells by using a mouse antiserum generated against the
      purified fusion protein showed that enolase is not located on the surface of C.
      albicans. Recombinant C. albicans enolase will be useful in understanding the
      pathogenesis and host immune response in disseminated candidiasis, since enolase
      is an immunodominant antigen which circulates during disseminated infections.

PMID- 1400229
TI  - Construction of a Helicobacter pylori genome map and demonstration of diversity
      at the genome level.
AB  - Genomic DNA from 30 strains of Helicobacter pylori was subjected to pulsed-field
      gel electrophoresis (PFGE) after digestion with NotI and NruI. The genome sizes
      of the strains ranged from 1.6 to 1.73 Mb, with an average size of 1.67 Mb. By
      using NotI and NruI, a circular map of H. pylori UA802 (1.7 Mb) which contained
      three copies of 16S and 23S rRNA genes was constructed. An unusual feature of the
      H. pylori genome was the separate location of at least two copies of 16S and 23S
      rRNA genes. Almost all strains had different PFGE patterns after NotI and NruI
      digestion, suggesting that the H. pylori genome possesses a considerable degree
      of genetic variability. However, three strains from different sites (the fundus,
      antrum, and body of the stomach) within the same patient gave identical PFGE
      patterns. The genomic pattern of individual isolates remained constant during
      multiple subcultures in vitro. The reason for the genetic diversity observed
      among H. pylori strains remains to be explained.

PMID- 1400230
TI  - ToxR proteins with substitutions in residues conserved with OmpR fail to activate
      transcription from the cholera toxin promoter.
AB  - The ToxR protein of Vibrio cholerae is an integral membrane protein that
      coordinately regulates the expression of virulence genes required for successful
      infection. ToxR has been shown to bind directly to and activate transcription of
      the cholera toxin (ctx) promoter. Within the amino-terminal cytoplasmic region of
      ToxR, several amino acids are strictly conserved among ToxR, OmpR, and the other
      members of a family of bacterial regulatory proteins. To better understand the
      function of this region, two approaches were taken: conserved residues were
      changed by site-directed mutagenesis, and random mutations that eliminated ToxR
      mediated transcriptional activation were isolated. Several classes of mutations
      were identified: those that abolish promoter DNA binding and transcriptional
      activation (toxR R96K, toxR R68K, and toxR R68L), those that abolish
      transcriptional activation but retain the ability to bind promoter DNA (toxR
      R96L), and those that have an intermediate phenotype (toxR R77L, toxR E51K, and
      toxR E51D). The toxR E51K allele had reduced activity in both Escherichia coli
      and V. cholerae but also exerted a dominant-negative effect over wild-type ToxR
      when assayed in V. cholerae. This result provides additional evidence that ToxR
      acts as an oligomer in the transcriptional activation process. From this
      mutational analysis of conserved amino acid residues within the OmpR-homologous
      region of ToxR, we conclude that this region is essential for transcriptional
      activation at the level of DNA binding and other steps that lead to activation of
      the ctx promoter.

PMID- 1400231
TI  - Effects of amino acid substitutions in the -10 binding region of sigma E from
      Bacillus subtilis.
AB  - The sigma subunit of bacterial RNA polymerase is required for specific binding to
      promoters. One region in most sigma factors makes sequence-specific contacts at
      the -10 region of its cognate promoters. To test the role of the amino acids in
      this -10 binding region, we examined the effects of 49 single-amino-acid
      substitutions in sigma E from Bacillus subtilis. We assayed the effect of each
      amino acid substitution on spore formation because sigma E is essential for
      endospore formation in B. subtilis. Our results showed that substitutions at
      several positions, including the highly conserved aromatic amino acid at position
      102, had little or no detectable effect. Substitutions at another position,
      position 117, produced dominant negative mutations; we suggest that these
      mutations allow RNA polymerase containing the mutant sigma factor to bind
      specifically to promoters but prevent transcription initiation. Of the recessive
      defective alleles, those that produced substitutions at positions 113, 115, and
      120 produced the most defective sigma factors. These results suggest that the
      residues at or near these positions in wild-type sigma E play important roles in
      sigma E function.

PMID- 1400233
TI  - Tripartite structure of the Saccharomyces cerevisiae arginase (CAR1) gene inducer
      responsive upstream activation sequence.
AB  - Arginase (CAR1) gene expression in Saccharomyces cerevisiae is induced by
      arginine. The 5' regulatory region of CAR1 contains four separable regulatory
      elements--two inducer-independent upstream activation sequences (UASs) (UASC1 and
      UASC2), an inducer-dependent UAS (UASI), and an upstream repression sequence
      (URS1) which negatively regulates CAR1 and many other yeast genes. Here we
      demonstrate that three homologous DNA sequences originally reported to be present
      in the inducer-responsive UASI are in fact three exchangeable elements (UASI-A,
      UASI-B, and UASI-C). Although two of these elements, either the same or different
      ones, are required for transcriptional activation to occur, all three are
      required for maximal levels of induction. The elements operate in all
      orientations relative to one another and to the TATA sequence. All three UASI
      elements bind protein(s); protein binding does not require arginine or
      overproduction of any of the putative arginine pathway regulatory proteins. The
      UASI-protein complex was also observed even when extracts were derived from
      arg80/argRI or arg81/argRII deletion mutants. Similar sequences situated upstream
      of ARG5,6 and ARG3 and reported to negatively regulate their expression are able
      to functionally substitute for the CAR1 UASI elements and mediate reporter gene
      expression.

PMID- 1400232
TI  - Beta-succinyl-coenzyme A synthetase from Trichomonas vaginalis is a soluble
      hydrogenosomal protein with an amino-terminal sequence that resembles
      mitochondrial presequences.
AB  - We describe studies directed toward understanding the biogenesis and origin of
      the hydrogenosome, an unusual organelle found exclusively in certain anaerobic
      eukaryotes that lack mitochondria. Hydrogenosomes are involved in fermentative
      carbohydrate metabolism and are proposed to have arisen through conversion of
      mitochondria or via endosymbiosis with an anaerobic bacterium. We cloned a gene
      encoding the beta subunit of the hydrogenosomal protein succinyl-coenzyme A
      synthetase (beta-SCS) and isolated the protein from Trichomonas vaginalis. The T.
      vaginalis beta-SCS gene encodes a protein with a calculated molecular mass of
      43,980 Da that has 43% amino acid identity (65% similarity) with beta-SCS from
      Escherichia coli. The trichomonad protein partitions into the soluble fraction of
      hydrogenosomes treated with sodium carbonate at high pH, consistent with a matrix
      localization within the organelle. The protein is encoded by a multigene family
      composed of at least three members. Amino-terminal sequencing of beta-SCS
      purified from T. vaginalis hydrogenosomes shows that the mature protein lacks the
      first nine amino acids encoded in the gene. This apparent amino-terminal leader
      sequence is strikingly similar to that of another hydrogenosomal protein and to
      mitochondrial presequences.

PMID- 1400234
TI  - Chemolithoautotrophic assimilation of dinitrogen by Streptomyces
      thermoautotrophicus UBT1: identification of an unusual N2-fixing system.
AB  - Streptomyces thermoautotrophicus UBT1, which was isolated previously from a
      burning charcoal pile, was shown to utilize N2 as a sole nitrogen source when
      growing chemolithoautotrophically with CO or H2 plus CO2 under aerobic conditions
      at 65 degrees C. Doubling times under diazotrophic conditions were 10 h. S.
      thermoautotrophicus is a new CO- or H2-oxidizing, obligately
      chemolithoautotrophic, thermophilic, free-living, aerobic, N2-fixing
      streptomycete. Its ability to fix N2 was also evident from (i) the incorporation
      of substantial amounts of 15N2 (about 13%) into cell material, (ii) the formation
      of H2 during diazotrophic growth, (iii) the repression of 15N2 assimilation and
      H2 formation by ammonia, and (iv) culture growth yields with N2 as a nitrogen
      source that were significantly higher than those without any added nitrogen
      compounds (ca. 2.4 versus < 0.1 mg [dry weight]). The N2-fixing system of S.
      thermoautotrophicus exhibited several properties not apparent in the diazotrophic
      bacteria studied so far, since it was (i) incapable of reducing acetylene to
      ethylene or ethane and (ii) resistant to inhibition by acetylene or ethylene (5%
      [vol/vol] each), CO (40 to 70% [vol/vol]), or H2 (40% [vol/vol]). Under stringent
      conditions, nifH and nifDK gene probes from Klebsiella pneumoniae did not
      hybridize with total DNA from S. thermoautotrophicus.

PMID- 1400236
TI  - Purification and characterization of phosphoenolpyruvate phosphomutase from
      Pseudomonas gladioli B-1.
AB  - Phosphoenolpyruvate phosphomutase (PEPPM) catalyzes C-P bond formation by
      intramolecular rearrangement of phosphoenolpyruvate to phosphonopyruvate (PnPy).
      We purified PEPPM from a gram-negative bacterium, Pseudomonas gladioli B-1
      isolated as a C-P compound producer. The equilibrium of this reaction favors the
      formation of the phosphate ester by cleaving the C-P bond of PnPy, but the C-P
      bond-forming reaction is physiologically significant. The C-P bond-forming
      activity of PEPPM was confirmed with a purified protein. The molecular mass of
      the native enzyme was estimated to be 263 and 220 kDa by gel filtration and
      polyacrylamide gel electrophoresis, respectively. A subunit molecular mass of 61
      kDa was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
      indicating that the native protein was a tetramer. The optimum pH and temperature
      were 7.5 to 8.0 and 40 degrees C, respectively. The Km value for PnPy was 19 +/-
      3.5 microM, and the maximum initial velocity of the conversion of PnPy to
      phosphoenolpyruvate was 200 microM/s/mg. PEPPM was activated by the presence of
      the divalent metal ion, and the Km values were 3.5 +/- 1.4 microM for Mg2+, 16 +/
      5 nM for Mn2+, 3.0 +/- 1.5 microM for Zn2+, and 1.2 +/- 0.2 microM for Co2+.

PMID- 1400235
TI  - The enhanced mutagenic potential of the MucAB proteins correlates with the highly
      efficient processing of the MucA protein.
AB  - Inducible mutagenesis in Escherichia coli requires the direct action of the
      chromosomally encoded UmuDC proteins or functional homologs found on certain
      naturally occurring plasmids. Although structurally similar, the five umu-like
      operons that have been characterized at the molecular level vary in their ability
      to enhance cellular and phage mutagenesis; of these operons, the mucAB genes from
      the N-group plasmid pKM101 are the most efficient at promoting mutagenesis.
      During the mutagenic process, UmuD is posttranslationally processed to an active
      form, UmuD'. To explain the more potent mutagenic efficiency of mucAB compared
      with that of umuDC it has been suggested that unlike UmuD, intact MucA is
      functional for mutagenesis. To examine this possibility, we have overproduced and
      purified the MucA protein. Although functionally similar to UmuD, MucA was
      cleaved much more rapidly both in vitro and in vivo than UmuD. In vivo,
      restoration of mutagenesis functions to normally nonmutable recA430, recA433,
      recA435, or recA730 delta(umuDC)595::cat strains by either MucA+ or mutant MucA
      protein correlated with the appearance of the cleavage product, MucA'. These
      results suggest that most of the differences in mutagenic phenotype exhibited by
      MucAB and UmuDC correlate with the efficiency of posttranslational processing of
      MucA and UmuD rather than an inherent activity of the unprocessed proteins.

PMID- 1400238
TI  - The Pseudomonas syringae pv. syringae 61 hrpH product, an envelope protein
      required for elicitation of the hypersensitive response in plants.
AB  - Pseudomonas syringae pv. syringae 61 contains a 25-kb cluster of hrp genes that
      are required for elicitation of the hypersensitive response (HR) in tobacco.
      TnphoA mutagenesis of cosmid pHIR11, which contains the hrp cluster, revealed two
      genes encoding exported or inner-membrane-spanning proteins (H.-C. Huang, S. W.
      Hutcheson, and A. Collmer, Mol. Plant-Microbe Interact. 4:469-476, 1991). The
      gene in complementation group X, designated hrpH, was subcloned on a 3.1-kb SalI
      fragment into pCPP30, a broad-host-range, mobilizable vector. The subclone
      restored the ability of hrpH mutant P. syringae pv. syringae 61-2089 to elicit
      the HR in tobacco. DNA sequence analysis of the 3.1-kb SalI fragment revealed a
      single open reading frame encoding an 81,956-Da preprotein with a typical amino
      terminal signal peptide and no likely inner-membrane-spanning hydrophobic
      regions. hrpH was expressed in the presence of [35S]methionine by using the T7
      RNA polymerase-promoter system and vector pT7-3 in Escherichia coli and was shown
      to encode a protein with an apparent molecular weight of 83,000 on sodium dodecyl
      sulfate-polyacrylamide gels. The HrpH protein in E. coli was located in the
      membrane fraction and was absent from the periplasm and cytoplasm. The HrpH
      protein possessed similarity with several outer membrane proteins that are known
      to be involved in protein or phage secretion, including the Klebsiella oxytoca
      PulD protein, the Yersinia enterocolitica YscC protein, and the pIV protein of
      filamentous coliphages. All of these proteins possess a possible secretion motif,
      GG(X)12VP(L/F)LXXIPXIGXL(F/L), near the carboxyl terminus, and they lack a
      carboxyl-terminal phenylalanine, in contrast to other outer membrane proteins
      with no known secretion function. These results suggest that the P. syringae pv.
      syringae HrpH protein is involved in the secretion of a proteinaceous HR
      elicitor.

PMID- 1400237
TI  - Sequence elements in the Escherichia coli araFGH promoter.
AB  - The Escherichia coli araFGH operon codes for proteins involved in the L-arabinose
      high-affinity transport system. Transcriptional regulation of the operon was
      studied by creating point mutations and deletions in the control region cloned
      into a GalK expression vector. The transcription start site was confirmed by RNA
      sequencing of transcripts. The sequences essential for polymerase function were
      localized by deletions and point mutations. Surprisingly, only a weak -10
      consensus sequence, and no -35 sequence is required. Mutation of a guanosine at
      position -12 greatly reduced promoter activity, which suggests important
      polymerase interactions with DNA between the usual -10 and -35 positions. A
      double mutation toward the consensus in the -10 region was required to create a
      promoter capable of significant AraC-independent transcription. These results
      show that the araFGH promoter structure is similar to that of the galP1 promoter
      and is substantially different from that of the araBAD promoter. The effects of
      11 mutations within the DNA region thought to bind the cyclic AMP receptor
      protein correlate well with the CRP consensus binding sequence and confirm that
      this region is responsible for cyclic AMP regulation. Deletion of the AraC
      binding site nearest the promoter, araFG1, eliminates arabinose regulation,
      whereas deletion of the upstream AraC binding site, araFG2, has only a slight
      effect on promoter activity.

PMID- 1400239
TI  - Evolutionary genetics of the proline permease gene (putP) and the control region
      of the proline utilization operon in populations of Salmonella and Escherichia
      coli.
AB  - Virtually complete sequences (1,467 bp) of the proline permease gene (putP) and
      complete sequences (416 to 422 bp) of the control region of the proline
      utilization operon were determined for 16 strains of Salmonella, representing all
      eight subspecies, and 13 strains of Escherichia coli recovered from natural
      populations. Strains of Salmonella and E. coli differed, on average, at 16.3% of
      putP nucleotide sites and 17.5% of control region sites; the average difference
      between strains was much larger for Salmonella strains (4.6% of putP sites and
      3.4% of control region sites) than for E. coli (2.4 and 0.9%, respectively).
      There was no difference in the distribution of polymorphic amino acid positions
      between the membrane-spanning and loop regions of the permease molecule, and
      rates of synonymous nucleotide substitution were virtually the same for the two
      domains. Statistical analysis yielded evidence of three probable cases of
      intragenic recombination, including the acquisition of a large segment of putP by
      strains of Salmonella subspecies VII from an unidentified source, the exchange of
      a 21-bp segment between two strains of E. coli, and the acquisition by one strain
      of E. coli of a cluster of 14 unique polymorphic control region sites from an
      unknown donor. An evolutionary tree for the putP and control region sequences was
      generally concordant with a tree for the gapA gene and a tree based on multilocus
      enzyme electrophoresis, thus providing evidence that for neither gene nor for
      enzyme genes in general has recombination occurred at rates sufficiently high or
      over regions sufficiently large to completely obscure phylogenetic relationships
      dependent on mutational divergence. It is suggested that the recombination rate
      varies among genes in relation to functional type, being highest for genes
      encoding cell surface and other proteins for which there is an adaptive advantage
      in structural diversity.

PMID- 1400240
TI  - Cloning, expression, and characterization of the Micromonospora viridifaciens
      neuraminidase gene in Streptomyces lividans.
AB  - We have cloned the Micromonospora viridifaciens neuraminidase (EC 3.2.1.18) gene
      (nedA) in Streptomyces lividans. This was accomplished by using the vector pIJ702
      and BglII-BclI libraries of M. viridifaciens chromosomal inserts created in S.
      lividans. The libraries were screened for the expression of neuraminidase by
      monitoring the cleavage of the fluorogenic neuraminidase substrate 2'-(4
      methylumbelliferyl)-alpha-D-N-acetyl-neuraminic acid. Positive clones (BG6, BG7,
      BC4, and BC8) contained the identical 2-kb BclI-BglII fragment and expressed
      neuraminidase efficiently and constitutively using its own promoter in the
      heterologous host. From the nucleotide sequence analysis, an open reading frame
      of 1,941 bp which encodes a polypeptide with an M(r) of 68,840 was detected. The
      deduced amino acid sequence has five Asp boxes, -Ser-X-Asp-X-Gly-X-Thr-Trp,
      showing great similarity to other bacterial and viral neuraminidases. We have
      also identified the catalytic domain by using truncated proteins produced in S.
      lividans.

PMID- 1400241
TI  - Function of the N-terminal half of RepA in activation of Rts1 ori.
AB  - The RepA protein of the Rts1 plasmid, consisting of 288 amino acids, is a trans
      acting protein essential for replication. A mutant repA gene, repA delta C143,
      carrying a deletion that removed the 143 C-terminal amino acids of RepA, could
      transform, but at a low frequency, an Escherichia coli polA strain, JG112, when
      repA delta C143 was cloned into pBR322 with Rts1 ori in the natural
      configuration. The transformation was less efficient without the dyad DnaA box in
      the ori region, and no transformation occurred at 42 degrees C, characteristic of
      Rts1 replication. A fusion of the 3'-terminal half of repA of the P1 plasmid to
      repA delta C143 yielded a pBR322 chimeric plasmid that contained Rts1 ori through
      hybrid (Rts1-P1) repA. This plasmid was maintained much more stably in JG112 at
      37 degrees C. At 42 degrees C, however, it was quite unstable. The overproduced
      hybrid RepA protein showed interference with mini-Rts1 replication in trans and
      also exhibited an autorepressor function, although both activities were
      decreased. These findings suggest that the N-terminal half of the RepA molecule
      of Rts1 is involved in the activation of the replication origin.

PMID- 1400242
TI  - Isolation and characterization of the high-affinity K(+)-translocating ATPase
      from Rhodobacter sphaeroides.
AB  - Cells of the purple nonsulfur bacterium Rhodobacter sphaeroides express a high
      affinity K+ uptake system when grown in media with low K+ concentrations. A
      vanadate-sensitive, K(+)-stimulated and Mg(2+)-stimulated ATPase was purified
      from membranes of these cells by solubilization with decyl-beta-D-maltoside in
      the presence of Escherichia coli phospholipids followed by triazine-dye affinity
      chromatography. This primary transport system has a substrate specificity and an
      inhibitor sensitivity closely similar to those of the Kdp ATPase from E. coli and
      is composed of three subunits with molecular masses of 70.0, 43.5, and 23.5 kDa.

PMID- 1400243
TI  - Identification and molecular analysis of a 63-kilodalton stress protein from
      Neisseria gonorrhoeae.
AB  - Iron limitation, glucose deprivation, and growth under low oxygen supply
      (environmental stress) increased the expression of several proteins of Neisseria
      gonorrhoeae, including a 63-kilodalton protein identified by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. This gonococcal stress protein
      (GSP63) was detected in the cytosol and copurified with lithium acetate-derived
      outer membranes. Successful purification of the protein was achieved by sucrose
      density gradient centrifugation and by chromatography on phenyl-Sepharose. Gel
      filtration of the purified protein revealed a molecular weight of approximately
      450,000, suggesting that in its native state, the protein consists of a multimer
      of six to eight subunits. Isoelectric focusing indicated a pI of 5.2.
      Immunoblotting experiments using a polyclonal antiserum raised against the
      purified protein demonstrated cross-reactivity with a protein of the same
      electrophoretic mobility as GSP63 in all eight gonococcal isolates tested. N
      terminal amino acid sequencing of the protein revealed up to 65% homology with
      members of the Hsp60 heat shock protein family, suggesting that GSP63 is related
      to this group of proteins. This relationship was further substantiated by the
      immunological cross-reactivity of GSP63 with mycobacterial Hsp60 and the ATP
      binding activity of the gonococcal stress protein.

PMID- 1400244
TI  - Roles of Salmonella typhimurium umuDC and samAB in UV mutagenesis and UV
      sensitivity.
AB  - Expression of the umuDC operon is required for UV mutagenesis and most chemical
      mutagenesis in Escherichia coli. The closely related species Salmonella
      typhimurium has two sets of umuDC-like operons; the samAB operon is located in a
      60-MDa cryptic plasmid, while the S. typhimurium umuDC (umuDCST) operon resides
      in a chromosome. The roles of these two umuDC-like operons in UV mutagenesis and
      UV sensitivity of S. typhimurium were investigated. A pBR322-derived plasmid
      carrying the samAB operon more efficiently restored UV mutability to a umuD44
      strain and a umuC122::Tn5 strain of E. coli than a plasmid carrying the umuDCST
      operon did. When the umuDCST operon was specifically deleted from the chromosome
      of S. typhimurium TA2659, the resulting strain was not UV mutable and was more
      sensitive to the killing effect of UV irradiation than the parent strain was.
      Curing of the 60-MDa cryptic plasmid carrying the samAB operon did not influence
      the UV mutability of strain TA2659 but did increase its resistance to UV killing.
      A pSC101-derived plasmid carrying the samAB operon did not restore UV mutability
      to a umuD44 strain of E. coli, whereas pBR322- or pBluescript-derived plasmids
      carrying the samAB operon efficiently did restore UV mutability. We concluded
      that the umuDCST operon plays a major role in UV mutagenesis in S. typhimurium
      and that the ability of the samAB operon to promote UV mutagenesis is strongly
      affected by gene dosage. Possible reasons for the poor ability of samAB to
      promote UV mutagenesis when it is present on low-copy-number plasmids are
      discussed.

PMID- 1400245
TI  - Cloning, nucleotide sequence, expression, and chromosomal location of ldh, the
      gene encoding L-(+)-lactate dehydrogenase, from Lactococcus lactis.
AB  - A gene (designated ldh) that encodes fructose-1,6-bisphosphate-activated L-(+)
      lactate dehydrogenase was cloned from Lactococcus lactis subsp. lactis. Plasmids
      containing ldh conferred fructose-1,6-bisphosphate-activated L-(+)-lactate
      dehydrogenase activity on Escherichia coli cells. This activity was conferred
      only when a promoter had been introduced into the plasmid to express the cloned
      ldh. The nucleotide sequence of ldh predicted a chain length of 324 amino acids
      and a subunit molecular weight of 34,910 for the enzyme, after removal of the N
      terminal methionine residue. Northern analyses of L. lactis subsp. lactis RNA
      showed that a 4.1-kb transcript hybridized strongly with ldh and that 1.2- and
      1.1-kb transcripts hybridized to much lesser extents. Promoter- and terminator
      cloning studies in which we used the vectors pGKV210 and pGKV259 in L. lactis
      subsp. lactis revealed that the 5' flanking DNA of ldh is devoid of transcription
      initiation signals and that transcription entering the 3' flanking DNA from
      either direction is efficiently terminated. These data and the data from Northern
      analyses led to the conclusion that ldh is expressed as the 3' gene of the 4.1-kb
      transcript and suggested that posttranscriptional processing yielded the shorter
      transcripts. We determined that ldh is located on the L. lactis subsp. lactis
      chromosome between coordinates 1.619 and 1.669 of the previously reported
      physical map (D. L. Tulloch, L. R. Finch, A. J. Hillier, and B. E. Davidson, J.
      Bacteriol. 173:2768-2775, 1991).

PMID- 1400246
TI  - DNA replication defect in Salmonella typhimurium mutants lacking the editing
      (epsilon) subunit of DNA polymerase III.
AB  - In Salmonella typhimurium, dnaQ null mutants (encoding the epsilon editing
      subunit of DNA polymerase III [Pol III]) exhibit a severe growth defect when the
      genetic background is otherwise wild type. Suppression of the growth defect
      requires both a mutation affecting the alpha (polymerase) subunit of DNA
      polymerase III and adequate levels of DNA polymerase I. In the present paper, we
      report on studies that clarify the nature of the physiological defect imposed by
      the loss of epsilon and the mechanism of its suppression. Unsuppressed dnaQ
      mutants exhibited chronic SOS induction, indicating exposure of single-stranded
      DNA in vivo, most likely as gaps in double-stranded DNA. Suppression of the
      growth defect was associated with suppression of SOS induction. Thus, Pol I and
      the mutant Pol III combined to reduce the formation of single-stranded DNA or
      accelerate its maturation to double-stranded DNA. Studies with mutants in major
      DNA repair pathways supported the view that the defect in DNA metabolism in dnaQ
      mutants was at the level of DNA replication rather than of repair. The
      requirement for Pol I was satisfied by alleles of the gene for Pol I encoding
      polymerase activity or by rat DNA polymerase beta (which exhibits polymerase
      activity only). Consequently, normal growth is restored to dnaQ mutants when
      sufficient polymerase activity is provided and this compensatory polymerase
      activity can function independently of Pol III. The high level of Pol I
      polymerase activity may be required to satisfy the increased demand for residual
      DNA synthesis at regions of single-stranded DNA generated by epsilon-minus pol
      III. The emphasis on adequate polymerase activity in dnaQ mutants is also
      observed in the purified alpha subunit containing the suppressor mutation, which
      exhibits a modestly elevated intrinsic polymerase activity relative to that of
      wild-type alpha.

PMID- 1400247
TI  - The virulence gene activator ToxT from Vibrio cholerae is a member of the AraC
      family of transcriptional activators.
AB  - Virulence gene expression in Vibrio cholerae is postulated to involve ToxR
      dependent activation of the toxT gene followed by ToxT activation of virulence
      genes, including several of those involved in biogenesis of the toxin-coregulated
      pilus. ToxR is a transmembrane, DNA-binding protein which is a member of the OmpR
      subclass of two-component activator systems in bacteria. Data presented in this
      report demonstrate that ToxT is similar to the AraC family of transcriptional
      activators identified in a variety of gram-negative bacteria. The toxT open
      reading frame begins approximately 200 nucleotides from the end of the tcpF gene,
      which is part of a cluster of genes responsible for production of the toxin
      coregulated pilus. Accumulation of toxT specific mRNA is ToxR dependent and is
      modulated by environmental conditions that modulate expression of the regulon.
      Within the intergenic region between tcpF and toxT is a potential stem-loop
      structure of an unusual nature which may play a role in regulating expression of
      toxT mRNA. Experiments with tcpF and toxT cloned behind a strong, constitutive
      promoter suggest that the two genes can be cotranscribed, but Northern (RNA) blot
      analysis of V. cholerae suggests that if they are, steady-state levels of their
      messages may be controlled by a posttranscriptional mechanism. Possible
      mechanisms for ToxR-dependent expression of toxT are discussed.

PMID- 1400249
TI  - Cloning and characterization of a Candida albicans maltase gene involved in
      sucrose utilization.
AB  - In order to isolate the structural gene involved in sucrose utilization, we
      screened a sucrose-induced Candida albicans cDNA library for clones expressing
      alpha-glucosidase activity. The C. albicans maltase structural gene (CAMAL2) was
      isolated. No other clones expressing alpha-glucosidase activity. were detected. A
      genomic CAMAL2 clone was obtained by screening a size-selected genomic library
      with the cDNA clone. DNA sequence analysis reveals that CAMAL2 encodes a 570
      amino-acid protein which shares 50% identity with the maltase structural gene
      (MAL62) of Saccharomyces carlsbergensis. The substrate specificity of the
      recombinant protein purified from Escherichia coli identifies the enzyme as a
      maltase. Northern (RNA) analysis reveals that transcription of CAMAL2 is induced
      by maltose and sucrose and repressed by glucose. These results suggest that
      assimilation of sucrose in C. albicans relies on an inducible maltase enzyme. The
      family of genes controlling sucrose utilization in C. albicans shares
      similarities with the MAL gene family of Saccharomyces cerevisiae and provides a
      model system for studying gene regulation in this pathogenic yeast.

PMID- 1400248
TI  - Molecular analysis of the glpFKX regions of Escherichia coli and Shigella
      flexneri.
AB  - We have identified a new gene, glpX, belonging to the glp regulon of Escherichia
      coli, located directly downstream of the glpK gene. The transcription of glpX is
      inducible with glycerol and sn-glycerol-3-phosphate and is constitutive in a glpR
      mutant. glpX is the third gene in the glpFKX operon. The function of GlpX remains
      unknown. GlpX has an apparent molecular weight of 40,000 on sodium dodecyl
      sulfate-polyacrylamide gels. In addition to determining the E. coli glpX
      sequence, we also sequenced the corresponding glpFKX region originating from
      Shigella flexneri, which after transfer into E. coli was instrumental in
      elucidating the function of glpF in glycerol transport (D. P. Richey and E. C. C.
      Lin, J. Bacteriol. 112:784-790, 1972). Sequencing of the glpFKX region of this
      hybrid strain revealed an amber mutation instead of the tryptophan 215 codon in
      glpF. The most striking difference between the E. coli and S. flexneri DNA was
      found directly behind glpK, where two repetitive (REP) sequences were present in
      S. flexneri, but not in the E. coli sequence. The presence or absence of these
      REP sequences had no effect on transport or on growth on glycerol. Not including
      the REP sequence-containing region, only 1.1% of a total of 2,167 bp sequenced
      was different in the two sequences. Comparison of the sequence with those in the
      EMBL data library revealed a 99% identity between the last third of glpX and the
      first part of a gene called mvrA. We show that the cloned mvrA gene (M. Morimyo,
      J. Bacteriol. 170:2136-2142, 1988) originated from the 88-min region of the
      Escherichia coli chromosome and not, as reported, from the 7-min region and that
      the gene product identified as MvrA is in fact encoded by a gene distal to glpX.

PMID- 1400250
TI  - Imprecise excision of plasmid pE194 from the chromosomes of Bacillus subtilis
      pE194 insertion strains.
AB  - Plasmid pE194 has been shown to be rescued by integration after cultivation of
      infected Bacillus subtilis recE4 cells at a restrictive high temperature. The
      plasmid is also spontaneously excised from the chromosome at a low frequency by
      precise or imprecise excision (J. Hofemeister, M. Israeli-Reches, and D. Dubnau,
      Mol. Gen. Genet. 189:58-68, 1983). We have investigated nine excision plasmids,
      carrying insert DNA 1 to 6 kbp in length, either in a complete pE194 or in a
      partially deleted pE194 copy. Type 1 (additive) excision plasmids have the left-
      and right-junction DNAs preserved as 13-bp direct repeats (5'-GGGGAGAAAACAT-3')
      corresponding to the region between positions 864 and 876 in pE194. In type 2
      (substitutive) excision plasmids, a conserved 13-bp sequence remains only at the
      right junction while the left junction has been deleted during the excision
      process. The type 3 excision plasmid carries at each junction the tetranucleotide
      5'-TCCC-3', present in pE194 between positions 1995 and 1998. Although we
      isolated the excision plasmids from different integration mutants, the insert
      DNAs of eight independently isolated plasmids showed striking sequence homology,
      suggesting that they originated from one distinct region of the B. subtilis
      chromosome. Thus, we postulate that imprecise excision of pE194 occurs most
      frequently after its translocation from the original insertion site into a
      preferred excision site within the host chromosome. The imprecise excision from
      this site occurs at excision breakpoints outside the pE194-chromosome junctions
      in a chromosomal region which remains to be investigated further.

PMID- 1400251
TI  - Molecular cloning, sequencing, and overexpression of the structural gene encoding
      the delta subunit of Escherichia coli DNA polymerase III holoenzyme.
AB  - Using an oligonucleotide hybridization probe, we have mapped the structural gene
      for the delta subunit of Escherichia coli DNA polymerase III holoenzyme to 14.6
      centisomes of the chromosome. This gene, designated holA, was cloned and
      sequenced. The sequence of holA matches precisely four amino acid sequences
      obtained for the amino terminus of delta and three internal tryptic peptides. A
      holA-overproducing plasmid that directs the expression of delta up to 4% of the
      soluble protein was constructed. Sequence analysis of holA revealed a 1,029-bp
      open reading frame that encodes a protein with a predicted molecular mass of
      38,703 Da. holA may reside downstream of rlpB in an operon, perhaps representing
      yet another link between structural genes for the DNA polymerase III holoenzyme
      and proteins involved in membrane biogenesis. These and other features are
      discussed in terms of genetic regulation of delta-subunit synthesis.

PMID- 1400252
TI  - The phenotypes of temperature-sensitive mini-RK2 replicons carrying mutations in
      the replication control gene trfA are suppressed nonspecifically by intragenic
      cop mutations.
AB  - The minimal replicon of the broad-host-range plasmid RK2 consists of the origin
      of vegetative replication (oriV) and a gene (trfA) encoding an essential
      replication protein that binds to short repeats in oriV. We report here the
      results of a DNA sequence analysis of seven unique mutants that are temperature
      sensitive for replication in Escherichia coli. The mutations (designated rts)
      were distributed throughout 40% of the downstream part of the trfA gene.
      Spontaneous revertants of the rts mutants were isolated, and further analysis of
      four such revertants demonstrated that the new phenotypes resulted from
      intragenic second-site copy up (cop) mutations. Subcloning experiments showed
      that all tested intragenic combinations of rts and cop mutations resulted in
      elimination or strong reduction of the temperature sensitivity of replication.
      This suppression was also observed under conditions where the mutant TrfA protein
      was provided in trans with respect to oriV, indicating that the reduction in
      temperature sensitivity could not be a TrfA protein dosage effect. The phenotypes
      of two of the cop mutants in Pseudomonas aeruginosa were analyzed; the results
      demonstrated that the mutants were either not functional or poorly functional in
      this host. The rts mutant plasmids were also reduced in their ability to
      replicate in P. aeruginosa, and the intragenic cop mutations did not improve the
      functionality of these mutants. The significance of the results is discussed in
      relation to current models of the mechanism of action of the TrfA protein.

PMID- 1400253
TI  - Functional roles assigned to the periplasmic, linker, and receiver domains of the
      Agrobacterium tumefaciens VirA protein.
AB  - VirA and VirG activate the Agrobacterium tumefaciens vir regulon in response to
      phenolic compounds, monosaccharides, and acidity released from plant wound sites.
      VirA contains an amino-terminal periplasmic domain and three cytoplasmic domains:
      a linker, a protein kinase, and a phosphoryl receiver. We constructed internal
      deletions of virA that truncate one or more domains and tested the ability of the
      resulting proteins to mediate environmentally responsive vir gene activation in
      vivo. The periplasmic domain is required for sensing of monosaccharides (in
      agreement with earlier results), while the linker domain is required for sensing
      of phenolic compounds and acidity. The phosphoryl receiver domain of VirA plays
      an inhibitory role in signal transduction that may be modulated by
      phosphorylation. The carboxy terminus of the protein was also dispensable for
      tumorigenesis, while the periplasmic domain was required.

PMID- 1400254
TI  - Altered-function mutations of the transcriptional regulatory gene virG of
      Agrobacterium tumefaciens.
AB  - Three point mutations were isolated in the Agrobacterium tumefaciens virG gene by
      screening for vir gene expression in the absence of added phenolic inducing
      compounds. All three mutations were localized in the predicted amino-terminal
      phosphoryl receiver domain of the protein. One mutant (N54D) bypasses the
      requirement for VirA and phenolic inducers both for transcriptional activation of
      all tested vir promoters and for plant tumorigenesis. This mutant also activates
      vir gene expression efficiently at neutral pH, indicating that the step in
      induction that is normally stimulated by acid pH occurs before or during VirG
      phosphorylation. The other two mutants (M13T and H15R) require VirA for activity
      but are sensitized to low levels of inducing stimuli.

PMID- 1400255
TI  - Regulation of the Staphylococcus aureus plasmid pI258 mercury resistance operon.
AB  - Experiments involving fusion between the Staphylococcus aureus plasmid pI258
      encoded mer operon and the reporter gene beta-lactamase, mutational analysis, and
      trans-complementation studies have shown that the merR gene of pI258, which shows
      DNA sequence similarity with known merR genes from other bacteria, regulates the
      expression of the mer operon in vivo. The merR gene product is a trans-acting
      protein that activates mer operon transcription in the presence of the inducers
      Hg2+ and Cd2+. A glutathione-S-transferase-MerR fusion protein specifically bound
      and protected a 27-nucleotide operator sequence from DNase I digestion. This
      operator sequence is highly homologous with mer operator sequences of other known
      systems.

PMID- 1400256
TI  - Influence of carbon source on cell surface topology of Thermomonospora curvata.
AB  - The appearance of cell surface protuberances in Thermomonospora curvata
      correlated with cell-bound exoenzymes which could be removed by brief sonication.
      Mycelia grown on cellulose or xylan had numerous protuberances and retained 20 to
      25% of endoglucanase and endoxylanase at cell surfaces, while those grown on
      pectin or starch had few protuberances and negligible bound pectinase or amylase.

PMID- 1400257
TI  - Nucleotide sequence of the R721 shufflon.
AB  - The shufflon is a DNA region that undergoes complex rearrangement mediated by the
      product of a putative site-specific recombinase gene, rci. The DNA sequences of
      the shufflon region and the rci gene of IncI2 plasmid R721 were determined. The
      R721 shufflon consists of three invertible DNA segments that are homologous to
      the shufflon segments found in IncI1 plasmid R64. Structural analysis of open
      reading frames indicated that the R721 shufflon possibly functions as a
      biological switch for selecting one of the six pilV genes in which the N-terminal
      region is constant and the C-terminal region is variable. The R721 rci gene was
      shown to encode a basic protein of 374 amino acid residues.

PMID- 1400259
TI  - Crystallization and preliminary X-ray studies of a Bacillus subtilis and Thermus
      thermophilus HB8 chimeric 3-isopropylmalate dehydrogenase and thermostable
      mutants of it.
AB  - A new type of chimeric 3-isopropylmalate dehydrogenase (2T2M6T) was produced by
      expressing the fused gene of Bacillus subtilis and Thermus thermophilus. The
      enzyme shows heat stability intermediate between those of the parents. The
      crystal of the enzyme belongs to the space group of P3(2)21, with cell dimensions
      of a = b = 78.9 A and c = 158.9 A. Two thermostable mutants of the chimeric
      enzyme were prepared by site-directed mutagenesis and then crystallized.

PMID- 1400258
TI  - Resolution of chromosomes III and VI of Aspergillus nidulans by pulsed-field gel
      electrophoresis shows that the penicillin biosynthetic pathway genes pcbAB, pcbC,
      and penDE are clustered on chromosome VI (3.0 megabases).
AB  - An improved electrophoretic molecular karyotype of Aspergillus nidulans ATCC
      28901 has been obtained by contour-clamped electric field gel electrophoresis,
      which separates seven chromosomal bands and allows resolution of chromosomes III
      and VI. The three genes of the penicillin biosynthetic pathway, pcbAB, pcbC, and
      penDE, encoding alpha-aminoadipyl-cysteinyl-valine synthetase, isopenicillin N
      synthase, and isopenicillin N acyltransferase, respectively, are clustered
      together on a chromosome of 3.0 Mg, corresponding to linkage group VI, whereas
      the argB gene was located on a chromosome of 3.4 Mb, corresponding to linkage
      group III. Three other strains of A. nidulans contained a modified chromosome III
      of about 3.1 Mb that overlaps with chromosome VI, forming a doublet. Resolution
      of chromosomes III and VI in strain ATCC 28901 allowed unequivocal mapping of the
      penicillin gene cluster on chromosome VI of A. nidulans.

PMID- 1400260
TI  - Tissue-specific regulation of renin-binding protein gene expression in rats.
AB  - Rat gene for renin-binding protein (RnBP) was shown to be expressed in the
      kidney, adrenal gland, brain, lung, spleen, ovary, testis, and heart. On sodium
      depletion and captopril administration, the rat showed a marked increase in the
      adrenal RnBP mRNA level and a slight decrease in the kidney RnBP mRNA level. In
      two-kidney, one clip hypertensive rats, the RnBP mRNA levels of the clipped and
      contralateral kidneys were unchanged and also its adrenal mRNA level was
      maintained at the control level. The recombinant rat RnBP was synthesized in
      Escherichia coli cells and purified to apparent homogeneity. The RnBP existed as
      a homodimer and formed a heterodimer with rat renin to inhibit renin activity
      extensively. Intravenous injection of the RnBP into rats resulted in a rapid and
      strong inhibition of plasma renin activity, which persisted at least for 2 h.
      These results suggest that the expression of RnBP gene in the kidney and adrenal
      gland is regulated independently, and the function of RnBP is related to
      electrolyte homeostasis, probably through the interaction with renin.

PMID- 1400261
TI  - Static and kinetic studies of calmodulin and melittin complex.
AB  - Ca2+ binding to calmodulin triggers conformational change of the protein which
      induces exposure of hydrophobic surfaces. Melittin has been believed to bind to
      Ca(2+)-bound calmodulin through the exposed hydrophobic surfaces. However,
      tryptophan fluorescence measurements and gel chromatography experiments with the
      melittin-calmodulin system revealed that melittin bound to calmodulin at zero
      salt concentration even in the absence of Ca2+; addition of salt removed melittin
      from Ca(2+)-free calmodulin. This means not only the hydrophobic interaction but
      also the electrostatic interaction contributes to the melittin-calmodulin
      binding. The fluorescence stopped-flow studies of the dissociation reaction of
      melittin-calmodulin complex revealed that Ca2+ removal from the complex induced a
      conformational change of calmodulin, resulting in reduction of the hydrophobic
      interaction between melittin and calmodulin, but the electrostatic interaction
      kept melittin still bound to calmodulin for a subsecond lag period, after which
      melittin dissociated from calmodulin. The fluorescence stopped-flow experiments
      on the dissociation reaction of complex of melittin and tryptic fragment(s) of
      calmodulin revealed that the lag period of the melittin dissociation reaction was
      attributable to the interaction between the C-terminal half of calmodulin and the
      C-terminal region of melittin.

PMID- 1400262
TI  - Topological disposition of UDP-glucuronyltransferase in rat liver microsomes.
AB  - The topological disposition of a form of UDP-glucuronyltransferase (called GT-1)
      in rat liver microsomes was examined. Concanavalin A-Sepharose failed to bind
      microsomal vesicles even though GT-1 has sugar chains of "high mannose" type,
      indicating that mannose-containing sugar chains of microsomal glycoproteins
      including GT-1 are not exposed to the outer surface of microsomal vesicles.
      Polyclonal antibodies raised against purified GT-1 could bind to microsomal
      vesicles, indicating that at least part of the GT-1 polypeptide chain is extruded
      to the outside of the microsomal membrane. Intact microsomal vesicles were
      digested with carboxypeptidase Y and then subjected to immunoblot analysis using
      the anti-GT-1 antibodies. It was thus found that the digestion resulted in
      cleavage of a C-terminal, 2-kDa fragment, leaving a 52-kDa fragment of GT-1 still
      tightly bound to the membrane. From these results, it is concluded that GT-1 is a
      transmembrane protein, which extrudes its C-terminal end (at least 2 kDa) to the
      outside of the membrane, whereas most of its polypeptide chain together with the
      sugar chains are located on the luminal side of the membrane.

PMID- 1400263
TI  - Molecular cloning of a rat liver cDNA encoding the 16 kDa subunit of vacuolar
      H(+)-ATPases: organellar and tissue distribution of 16 kDa proteolipids.
AB  - A cDNA (T3-L) encoding the 16 kDa subunit of vacuolar H(+)-ATPase was cloned from
      a cDNA library of rat liver. A polypeptide of 155 amino acids with a molecular
      mass of 15,807 Da (pI = 9.5) having four hydrophobic stretches was predicted. T3
      L polypeptide was 92% and 100% identical with the 16 kDa proteolipid of bovine
      chromaffin granule and that of mouse, respectively. Antisera raised against the
      NH2-terminal of the T3-L polypeptide reacted positively with the membrane ghosts
      of rat liver tritosomes and the partially purified H(+)-ATPase thereof. Western
      blotting of subcellular fractions with the antisera showed high abundance of 16
      kDa protein in the lysosomes, although a significant amount was also detected in
      the Golgi apparatus. Western blotting of rat tissues revealed high levels of 16
      kDa proteolipid in the brain and the kidney. Northern blots with T3-L similarly
      showed considerably high expression of T3-L mRNA in the brain and the kidney.
      Southern hybridization of rat genomic DNA with T3-L showed at most three distinct
      bands, regardless of the stringency of hybridization and whether hybridization
      was performed with its subfragments. This suggests the possibility of multiple
      (at least three) homologous/identical genes encoding 16 kDa proteolipid. The
      possible presence and significance of isoforms of 16 kDa proteolipid in rats are
      discussed.

PMID- 1400264
TI  - Effect of diolein on hydrolysis of phosphatidylcholine by phospholipase C from
      Clostridium perfringens.
AB  - The activity of phospholipase C from Clostridium perfringens on 1-palmitoyl-2
      oleoyl-sn-glycero-3-phosphocholine (POPC) as a monolayer at an air/water
      interface was examined. With a pure POPC monolayer, sharp cut-off of the enzyme
      activity was observed on increase in surface pressure. However, this cut-off
      disappeared on addition of a 0.3 molar fraction of 1,2-dioleoylglycerol (1,2-DO)
      to the monolayer. An abrupt change in the enzyme activity was observed with molar
      fractions of between 0.2 and 0.3 1,2-DO in the POPC monolayer at an initial
      surface pressure of 35 mN/m. For examination of the effect of 1,2-DO on the
      phospholipase C activity, the quantity of [125I]phospholipase C adsorbed to the
      surface was determined. The enzyme was found to be adsorbed nonspecifically to
      all lipid films except that of POPC only. The adsorption of enzyme was not
      affected by the presence or absence of Ca2+ and Zn2+. The rate constant for
      enzyme adsorption to a 1,2-DO film was 4.5 times that for its adsorption to a
      POPC film. The adsorption decreased linearly with increase in the surface
      concentration of POPC, and increased with increase in the surface concentration
      of 1,2-DO. These data suggest that 1,2-DO (a reaction product) regulates the
      interaction of phospholipase C with films containing substrate and may also
      regulate the enzyme activity.

PMID- 1400266
TI  - Purification and characterization of a novel dipeptidyl carboxypeptidase from a
      Streptomyces species.
AB  - An extracellular protease derived from the culture broth of a microorganism, a
      Streptomyces species, produced Boc-Pro-Pro and diproline from Boc-Pro-Pro-Pro
      Pro. The enzyme was purified 726-fold, with a yield of 2.6%, by ammonium sulfate
      fractionation, ion-exchange chromatography, and gel filtration chromatography.
      The molecular weight of the enzyme was determined to be 65,000 by gel filtration
      and 70,000 by SDS-PAGE. The enzyme released a C-terminal dipeptide from peptide
      substrates having a C-terminal proline and a penultimate proline or alanine
      residue, but did not hydrolyze angiotensin I or bradykinin. When the enzyme
      hydrolyzed Leu-Pro-Pro-Pro-Pro-Pro, it produced Leu-Pro-Pro-Pro and Pro-Pro
      before producing Leu-Pro. The enzyme thus seems to be a kind of dipeptidyl
      carboxypeptidase, its substrate specificity being very different from that of the
      well known dipeptidyl carboxypeptidases [EC 3.4.15.1] such as the angiotensin
      converting enzyme.

PMID- 1400265
TI  - Molecular cloning of a cDNA encoding a member of a novel cytochrome P450 family
      in the mollusc Lymnaea stagnalis.
AB  - We isolated a cDNA encoding a cytochrome P450 from the mollusc Lymnaea stagnalis.
      The mRNA is 2.1 nucleotides long and contains an open reading frame encoding a
      protein of 545 amino acids. A conserved home-binding domain, characteristic of
      cytochrome P450 proteins, is present in the deduced amino acid sequence. The
      Lymnaea cytochrome P450 protein shares less than 40% positional identity with any
      known member of the cytochrome P450 superfamily, and therefore, represents a
      separate family, which we propose to name CYP10. The CYP10 mRNA is shown to be
      uniquely and abundantly expressed in the female gonadotropic hormone producing
      dorsal bodies of L. stagnalis.

PMID- 1400267
TI  - Leucine dehydrogenase from Bacillus stearothermophilus: identification of active
      site lysine by modification with pyridoxal phosphate.
AB  - We have constructed an efficient expression plasmid for the leucine dehydrogenase
      gene previously cloned from Bacillus stearothermophilus. The recombinant enzyme
      was overproduced in Escherichia coli cells to a level of more than 30% of the
      total soluble protein upon induction with isopropyl beta-D-thiogalactopyranoside.
      The enzyme could be readily purified to homogeneity by heat treatment and a
      single step of ion-exchange chromatography. The purified enzyme was inactivated
      in a time-dependent manner upon incubation with pyridoxal 5'-phosphate (PLP)
      followed by reduction with sodium borohydride. The inactivation was completely
      prevented in the copresence of L-leucine and NAD+. Concomitantly with the
      inactivation, several molecules of PLP were incorporated into each subunit of the
      hexameric enzyme. Sequence analysis of the fluorescent peptides isolated from a
      proteolytic digest of the modified protein revealed that Lys80, Lys91, Lys206,
      and Lys265 were labeled. Among these residues, Lys80 was predominantly labeled
      and, in the presence of L-leucine and NAD+, was specifically protected from the
      labeling. Furthermore, a linear relationship of about 1:1 was observed between
      the extent of inactivation and the amount of PLP incorporated into Lys80. A
      slightly active mutant enzyme, in which Lys80 is replaced by Ala, was not
      inactivated at all by incubation with PLP, showing that the inactivation is
      correlated with the labeling of only Lys80. Lys80is conserved in the
      corresponding regions of all the amino acid dehydrogenase sequences reported to
      date. These results suggest that Lys80 is located at the active site and plays an
      important role in the catalytic function of leucine dehydrogenase.

PMID- 1400268
TI  - Conversion of pyridylamino sugar chains to 1-amino-1-deoxy derivatives,
      intermediates for tagging with fluorescein and biotin.
AB  - Pyridylamino (PA) derivatives of sugar chains were converted to 1-amino-1-deoxy
      derivatives. PA-lactose as a model compound was reduced with hydrogen, then
      treated with hydrazine. The product obtained was identified as 1-amino-1
      deoxylactitol by mass spectrometry and chromatography with 1-amino-1
      deoxylactitol as standard. PA-N-acetylglucosamine was converted to 1-amino-1
      deoxy-N-acetylglucosaminitol under the same conditions. As an application, Man
      alpha 1-6(Man alpha 1-3)Man alpha 1- 6(Man alpha 1-2Man alpha 1-3)-Man beta 1
      4GlcNAc beta 1-4GlcNAc-PA was converted to the 1-amino-1-deoxy derivative, which
      was further derivatized with fluorescein isothiocyanate or biotin sulfo-N-hydroxy
      succinimide ester. Binding of these derivatives to concanavalin A dot-blotted on
      a nitrocellulose membrane was confirmed by fluorescence and by streptavidin
      peroxidase conjugate. This conversion allowed replacement of the PA-group in PA
      sugar chains which can be easily purified from glycoconjugates.

PMID- 1400269
TI  - Twenty-eight-kilodalton phosphorylatable calcium- and lipid-binding proteins
      purified from Physarum plasmodium.
AB  - Two 28-kDa calcium- and lipid-binding proteins were isolated from a detergent
      insoluble fraction of the Physarum plasmodium. Both proteins have molecular
      masses of approximately 28 kDa by SDS-PAGE. The protein designated 28K-I has a
      slightly lower mobility than that designated 28K-II. The purified 28K-I has a
      dissociation constant of 1.0 microM for Ca2+ ions, while the 28K-II has two
      different dissociation constants: one of 0.32 microM and the other of 3.2 mM. The
      28K-I binds to liposomes at Ca2+ concentrations higher than 1.0 microM and has a
      dissociation constant for lipid of 34 micrograms/ml at 10 microM Ca2+. The 28K-II
      binds to liposomes at concentrations of Ca2+ above the mM range and has a
      dissociation constant of 36 micrograms/ml for lipid at 2 mM Ca2+. There is no
      evidence of actin-binding activity by either of the 28-kDa (28K) proteins. The
      28K proteins crossreacted with an antiserum against chicken brush border
      calpactin I. The two proteins have quite different phosphorylation levels between
      a fraction prepared from the cytosolic endoplasm and a fraction prepared from the
      whole cell. The 28K proteins may play some role in the membrane structure
      dynamics of the cortical gel layer.

PMID- 1400270
TI  - A novel difucosylated neutral glycosphingolipid from the eggs of the sea urchin,
      Hemicentrotus pulcherrimus: I. Purification and structural determination of the
      glycolipid.
AB  - A novel fucose-containing neutral glycosphingolipid (GL-5) was purified from the
      eggs of the sea urchin, Hemicentrotus pulcherrimus. The chemical structure was
      determined to be Fuc alpha 1-3GalNAc beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-4Glc
      beta 1-1Cer by methylation analysis, partial acid hydrolysis, fast atom
      bombardment mass spectrometry, and proton nuclear magnetic resonance
      spectroscopy. The unique characteristics of GL-5 are that: the reducing terminal
      disaccharide portion is not Gal beta 1-4Glc but GlcNAc beta 1-4Glc; it includes a
      GalNAc beta 1-4GlcNAc sequence and a Fuc-GalNAc linkage; the defucosylated core
      is a novel trisaccharide chain; and the sugar structure is one of the smallest
      ever characterized for a difucosylated glycolipid. The major fatty acids were
      22:1 and 22h:1, and about 30% of the total acids was 2-hydroxylated. All the long
      chain bases were phytosphingosines, of which about 90% was n-t18:0. The
      similarity of the ceramide moiety to that of glucosylceramide from the same eggs
      [Kubo, H. et al. (1992) J. Biochem. 111, 726-731] suggests a close biosynthetic
      relationship between GL-5 and the glucosylceramide.

PMID- 1400271
TI  - A novel difucosylated neutral glycosphingolipid from the eggs of the sea urchin,
      Hemicentrotus pulcherrimus: II. Structural determination by two-dimensional NMR.
AB  - A novel fucosylglycolipid from the eggs of the sea urchin, Hemicentrotus
      pulcherrimus, was determined by using two-dimensional NMR methods. Subspectra
      extraction by the homonuclear Hartmann-Hahn method was useful for identification
      of the individual sugar components. The homonuclear Hartmann-Hahn and double
      quantum-filtered correlated spectra were analyzed to establish the assignments of
      sugar proton resonances. On the basis of the resonance assignments, the linkages
      of the individual sugar components were determined to be as follows. [formula:
      see text] This glycolipid contains a novel skeletal structure with the linkages
      of GalNAc beta 1-4GlcNAc beta 1-4Glc beta. We also observed that 2-hydroxylation
      of the fatty acids induced appreciable chemical shift changes of the proton
      resonances of the phytosphingosine moiety as well as the anomeric proton
      resonance of the reducing terminal glucose.

PMID- 1400272
TI  - General purpose medical imaging databases: three models.
AB  - A useful general purpose digital medical image database project can begin with
      relatively simple and low-cost capabilities provided by a computer operating
      system. As the amount of data and the number of users grow, transition to a
      relational database model becomes appropriate. When multiple database systems are
      present, a flexible front end can provide sophisticated querying capabilities
      that bridge the systems, while hiding the complexities of the multiple systems
      from the user.

PMID- 1400273
TI  - Update in biomedical visualization: the professional communicator's role.
AB  - Health science communications professionals span a broad range of disciplines,
      each bringing a distinctly different focus and set of cognitive skills to bear
      upon information technologies. Nowhere is this more apparent than in
      biocommunications service units and academic programs. Until now, most faculty
      from visually-based disciplines were rarely required to generate research or
      project contracts. This is changing; new demands are being made for allied health
      faculty to obtain research grants and for academic health science centers to
      forge ventures with the private sector. Visualization in scientific computing
      offers new avenues for these activities.

PMID- 1400274
TI  - Optical technology: making the simulator portable.
AB  - Optical disc technology can be either analog or digital. Analog (videodiscs)
      simulation programs are available for the allied health professions educator to
      incorporate into the curriculum. Digital optical discs, currently available in
      three formats, follow standards that have been adopted by the International
      Standards Organization. The formats differ in the amount of information they can
      accommodate and their practical use in the health professions curriculum.

PMID- 1400275
TI  - Instructional multimedia computing in the health sciences.
AB  - This article focuses on the development and utilization of interactive videodisc
      (IVD) and multimedia instruction in the health sciences. The characteristics of
      IVD and multimedia are outlined and the four levels of IVD systems that can be
      used in health science education are described. The advantages of utilization of
      videodisc or multimedia materials are presented, as well as instructional
      approaches. Potential applications such as simulations, tutorials, role-modeling,
      and drill-and-practice are described. Research findings, levels of curricular
      integration, instructional delivery, and courseware networking are also
      described. The article concludes with suggestions for institutional development
      of IVD materials or the incorporation of off-the-shelf programs into health
      science curricula.

PMID- 1400276
TI  - The need for a national information infrastructure.

PMID- 1400277
TI  - Partial characterization of the inhibitory effect of lipid peroxidation on the
      ouabain-insensitive Na-ATPase of rat kidney cortex plasma membranes.
AB  - The present work evaluates the effect of lipid peroxidation on the ouabain
      insensitive Na-ATPase of basolateral plasma membranes from rat kidney proximal
      tubular cells as an indirect way to study the lipid dependence of this enzyme. An
      inverse relationship between lipid peroxidation and Na-ATPase activity was found.
      This effect was due neither to a change in the optimal Km of the system for Na+
      nor for the substrate Mg:ATP, nor the optimal pH value of the medium. The optimal
      temperature value, however, was shifted toward a higher value. There was also an
      increase of the apparent energy of activation in the region of temperatures above
      the transition point (20 degrees C) with increase in lipid peroxidation.
      Peroxidized membranes incubated with phosphatidylcholine from soybean restored
      their Na-ATPase activity. On the other hand, the Na-ATPase activity was sensitive
      to oleoly lysophosphatidylcholine. These results suggest that lipid peroxidation
      might be affecting the Na-ATPase activity through either an increase of
      peroxidized phospholipids, which might change the membrane fluidity of the lipid
      microenvironment of the ATPase molecules, or through a direct effect of
      lysophospholipids released during the lipid peroxidation.

PMID- 1400278
TI  - V-type ATPases. Introduction.

PMID- 1400279
TI  - Structure and properties of the coated vesicle (H+)-ATPase.
AB  - Clathrin-coated vesicles play an important role in both receptor-mediated
      endocytosis and intracellular membrane traffic in eukaryotic cells. The coated
      vesicle (H+)-ATPase functions to provide the acidic environment within endosomes
      and other intracellular compartments necessary for receptor recycling and
      intracellular membrane traffic. The coated vesicle (H+)-ATPase is composed of
      nine different subunits which are divided into two distinct domains. The
      peripheral V1 domain, which has the structure 73(3):58(3):40(1):34(1):33(1),
      possesses the nucleotide binding sites of the (H+)-ATPase. The integral V0
      domain, which has the composition 100(1):38(1):19(1):17(6), contains the pathway
      for proton conduction across the membrane. Topographical analysis indicates a
      structure for the coated vesicle (H+)-ATPase very similar to that of the F-type
      ATPases. Reassembly studies have allowed us to probe the function of particular
      subunits in this complex and the activity properties of the separate domains.
      These studies have led to insights into possible mechanisms of regulating
      vacuolar acidification.

PMID- 1400280
TI  - The structure and biochemistry of the vacuolar H+ ATPase in proximal and distal
      urinary acidification.
AB  - Vacuolar H+ ATPases participate in renal hydrogen ion secretion in both the
      proximal and distal nephron. These plasma membrane forms of the vacuolar H+
      ATPase are regulated physiologically to maintain the acid-base balance of the
      organism. Proton transporting renal cells have requirements for constitutive
      acidification of intracellular compartments for normal endocytic and secretory
      functions. Recent experiments have begun to reveal how the kidney regulates these
      proton pumps independently. Vacuolar H+ ATPases are a family of structurally
      similar enzyme which differ in the composition of specific subunits. Cytosolic
      regulatory enzymes are present in renal cells which may affect vacuolar H+
      ATPases in certain membrane compartments selectively. The vacuolar H+ ATPase in
      the plasma membrane of intercalated cells resides in a specialized proton
      transporting apparatus that translocates the enzyme between an intracellular
      membrane pool and the plasma membrane in response to physiologic stimuli.

PMID- 1400281
TI  - The vacuolar ATPase of Neurospora crassa.
AB  - The filamentous fungus Neurospora crassa has many small vacuoles which, like
      mammalian lysosomes, contain hydrolytic enzymes. They also store large amounts of
      phosphate and basic amino acids. To generate an acidic interior and to drive the
      transport of small molecules, the vacuolar membranes are densely studded with a
      proton-pumping ATPase. The vacuolar ATPase is a large enzyme, composed of 8-10
      subunits. These subunits are arranged into two sectors, a complex of peripheral
      subunits called V1 and an integral membrane complex called V0. Genes encoding
      three of the subunits have been isolated. vma-1 and vma-2 encode polypeptides
      homologous to the alpha and beta subunits of F-type ATPases. These subunits
      appear to contain the sites of ATP binding and hydrolysis. vma-3 encodes a highly
      hydrophobic polypeptide homologous to the proteolipid subunit of vacuolar ATPases
      from other organisms. This subunit may form part of the proton-containing pathway
      through the membrane. We have examined the structures of the genes and attempted
      to inactivate them.

PMID- 1400283
TI  - Subunit composition, biosynthesis, and assembly of the yeast vacuolar proton
      translocating ATPase.
AB  - The yeast vacuole is acidified by a vacuolar proton-translocating ATPase (H(+)
      ATPase) that closely resembles the vacuolar H(+)-ATPases of other fungi, animals,
      and plants. The yeast enzyme is purified as a complex of eight subunits, which
      include both integral and peripheral membrane proteins. The genes for seven of
      these subunits have been cloned, and mutant strains lacking each of the subunits
      (vma mutants) have been constructed. Disruption of any of the subunit genes
      appears to abolish the function of the vacuolar H(+)-ATPase, supporting the
      subunit composition derived from biochemical studies. Genetic studies of vacuolar
      acidification have also revealed an additional set of gene products that are
      required for vacuolar H(+)-ATPase activity, but may not be part of the final
      enzyme complex. The biosynthesis, assembly, and targeting of the enzyme is being
      elucidated by biochemical and cell biological studies of the vma mutants. Initial
      results suggest that the peripheral and integral membrane subunits may be
      independently assembled.

PMID- 1400282
TI  - Vacuolar H(+)-translocating ATPases from plants: structure, function, and
      isoforms.
AB  - The vacuolar H(+)-translocating ATPase (V-type ATPase) plays a central role in
      the growth and development of plant cells. In a mature cell, the vacuole is the
      largest intracellular compartment, occupying about 90% of the cell volume. The
      proton electrochemical gradient (acid inside) formed by the vacuolar ATPase
      provides the primary driving force for the transport of numerous ions and
      metabolites against their electrochemical gradients. The uptake and release of
      solutes across the vacuolar membrane is fundamental to many cellular processes,
      such as osmoregulation, signal transduction, and metabolic regulation. Vacuolar
      ATPases may also reside on endomembranes, such as Golgi and coated vesicles, and
      thus may participate in intracellular membrane traffic, sorting, and secretion.
      Plant vacuolar ATPases are large complexes (400-650 kDa) composed of 7-10
      different subunits. The peripheral sector of 5-6 subunits includes the nucleotide
      binding catalytic and regulatory subunits of approximately 70 and approximately
      60 kDa, respectively. Six copies of the 16-kDa proteolipid together with 1-3
      other subunits make up the integral sector that forms the H+ conducting pathway.
      Isoforms of plant vacuolar ATPases are suggested by the variations in subunit
      composition observed among and within plant species, and by the presence of a
      small multigene family encoding the 16-kDa and 70-kDa subunits. Multiple genes
      may encode isoforms with specific properties required to serve the diverse
      functions of vacuoles and endomembrane compartments.

PMID- 1400284
TI  - Genetic and cell biological aspects of the yeast vacuolar H(+)-ATPase.
AB  - The yeast vacuolar proton-translocating ATPase is a member of the third class of
      H(+)-pumping ATPase. A family of this type of H(+)-ATPase is now known to be
      ubiquitously distributed in eukaryotic vacuo-lysosomal organelles and
      archaebacteria. Nine VMA genes that are indispensable for expression of the
      enzyme activity have been cloned and characterized in the yeast Saccharomyces
      cerevisiae. This review summarizes currently available information on the VMA
      genes and cell biological functions of the VMA gene products.

PMID- 1400285
TI  - Structural conservation and functional diversity of V-ATPases.
AB  - The vacuolar system of eukaryotic cells contains a large number of organelles
      that are primary energized by an H(+)-ATPase that was named V-ATPase. The
      structure and function of V-ATPases from various sources was extensively studied
      in the last few years. Several genes encoding subunits of the enzyme were cloned
      and sequenced. The sequence information revealed the relations between V-ATPases
      and F-ATPases that evolved from common ancestral genes. The two families of
      proton pumps share structural and functional similarity. They contain distinct
      peripheral catalytic sectors and hydrophobic membrane sectors. Genes encoding
      subunits of V-ATPase in yeast cells were interrupted to yield mutants that are
      devoid of the enzyme and are sensitive to pH and calcium concentrations in the
      medium. The mutants were used to study structure, function, molecular biology,
      and biogenesis of the V-ATPase. They also shed light on the functional assembly
      of the enzyme in the vacuolar system.

PMID- 1400287
TI  - Signal transduction in bacterial chemotaxis.

PMID- 1400286
TI  - Evolution of structure and function of V-ATPases.
AB  - Proton pumping ATPases/ATPsynthases are found in all groups of present-day
      organisms. The structure of V- and F-type ATPases/ATP synthases is very conserved
      throughout evolution. Sequence analysis shows that the V- and F-type ATPases
      evolved from the same enzyme already present in the last common ancestor of all
      known extant life forms. The catalytic and noncatalytic subunits found in the
      dissociable head groups of the V/F-type ATPases are paralogous subunits, i.e.,
      these two types of subunits evolved from a common ancestral gene. The gene
      duplication giving rise to these two genes (i.e., encoding the catalytic and
      noncatalytic subunits) predates the time of the last common ancestor. Mapping of
      gene duplication events that occurred in the evolution of the proteolipid, the
      noncatalytic and the catalytic subunits, onto the tree of life leads to a
      prediction for the likely subunit structure of the encoded ATPases. A correlation
      between structure and function of V/F-ATPases has been established for present
      day organisms. Implications resulting from this correlation for the bioenergetics
      operative in proto-eukaryotes and in the last common ancestor are presented. The
      similarities of the V/F-ATPase subunits to an ATPase-like protein that was
      implicated to play a role in flagellar assembly are evaluated. Different V-ATPase
      isoforms have been detected in some higher eukaryotes. These data are analyzed
      with respect to the possible function of the different isoforms (tissue specific,
      organelle specific) and with respect to the point in their evolution when these
      gene duplications giving rise to the isoforms had occurred, i.e., how far these
      isoforms are distributed.

PMID- 1400288
TI  - Absence of G(i) proteins in the Sf9 insect cell. Characterization of the
      uncoupled recombinant N-formyl peptide receptor.
AB  - We investigated the interaction of the N-formyl peptide receptor (NFPR) with G
      proteins in infected Sf9 insect cells expressing the recombinant NFPR.
      Recombinant receptor expression of up to 27 pmol/mg protein was achieved in these
      cells. The receptor was recognized by an antiserum raised against an NFPR
      carboxyl-terminal peptide, and displayed specific and saturable binding of the
      formyl peptide ligand fMet-Leu-[3H]Phe. Scatchard analysis of the binding data
      yielded a dissociation constant of approximately 62 nM, a binding affinity of 60-
      to 120-fold lower than that of the high affinity sites in neutrophils and in
      transfected mammalian cell lines expressing the NFPR. That this low binding
      affinity was due to a lack of receptor coupling to G protein was suggested by the
      failure of guanine nucleotides to regulate receptor affinity and by the lack of
      formyl peptide-stimulated GTPase activity in these cells. Furthermore,
      immunoblotting with an anti-G(i) antibody and ADP-ribosylation experiments
      indicated that the approximately 40-kDa G(i) alpha subunit, which couples to the
      NFPR in neutrophils, is not present in Sf9 cell membranes. Thus, the current
      study provides for the first time evidence that a major G protein is absent in
      the Sf9 insect cells. Potential applications of the Sf9 system for in vitro
      reconstitution of the NFPR-G protein interaction are discussed.

PMID- 1400289
TI  - A novel mechanism for regulation of vacuolar acidification.
AB  - We have recently demonstrated that Cys-254 of the 73-kDa A subunit of the
      clathrin-coated vesicle (H+)-ATPase is responsible for sensitivity of the enzyme
      to sulfhydryl reagents (Feng, Y., and Forgac, M. (1992) J. Biol. Chem. 267, 5817
      5822). In the present study we observe that for the purified enzyme, disulfide
      bond formation causes inactivation of proton transport which is reversed by
      dithiothreitol (DTT). DTT also restores activity of the oxidized enzyme following
      treatment with N-ethylmaleimide (NEM). These results indicate that disulfide bond
      formation between the NEM-reactive cysteine (Cys-254) and a closely proximal
      cysteine residue leads to inactivation of the (H+)-ATPase. To test whether
      sulfhydryl-disulfide bond interchange may play a role in regulating vacuolar
      acidification in vivo, we have determined what fraction of the (H+)-ATPase is
      disulfide-bonded in native clathrin-coated vesicles. Vesicles were isolated under
      conditions that prevent any change in the oxidation state of the sulfhydryl
      groups. NEM treatment of vesicles causes nearly complete loss of activity while
      subsequent treatment with DTT restores 50% of the activity of the fully reduced
      vesicles. By contrast, treatment of fully reduced vesicles with NEM leads to
      inactivation which is not reversed by DTT. These results indicate that a
      significant fraction of the clathrin-coated vesicle (H+)-ATPase exists in an
      inactive, disulfide-bonded state and suggest that sulfhydryl-disulfide bond
      interconversion may play a role in controlling vacuolar (H+)-ATPase (V-ATPase)
      activity in vivo.

PMID- 1400290
TI  - Chloroplast envelope proteins are encoded by the chloroplast genome of
      Chlamydomonas reinhardtii.
AB  - To characterize envelope proteins encoded by the chloroplast genome, envelopes
      were isolated from Chlamydomonas reinhardtii cells labeled with [35S] sulfate
      while blocking synthesis by cytoplasmic ribosomes. One and two-dimensional gel
      electrophoresis of envelopes and fluorography revealed four highly labeled
      proteins. Two with masses of 29 and 30 kDa and pI 5.5 were absent from the stroma
      and thylakoid fractions, while the others at 54 kDa, pI 5.2 and 61 kDa, pI 5.4
      were detected there in smaller amounts. The 29- and 30-kDa proteins were
      associated with outer envelope membranes separated from inner envelope membranes
      after chloroplast lysis in hypertonic solution. A 32-kDa protein not labeled by
      [35S]sulfate was found exclusively in the inner membrane fraction, suggesting the
      existence of a phosphate translocator in C. reinhardtii. To identify envelope
      proteins exposed on the chloroplast surface, isolated active chloroplasts were
      surface-labeled with 125I and lactoperoxidase. The 54-kDa, pI 5.2 protein as well
      as a protein corresponding to either of the 29- or 30-kDa proteins described
      above were among the labeled components. These results show that envelope
      proteins of C. reinhardtii are encoded by the chloroplast genome and two are
      located on the outer envelope membranes.

PMID- 1400292
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin causes reduction of glucose transporting
      activities in the plasma membranes of adipose tissue and pancreas from the guinea
      pig.
AB  - Toxicity from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure results in
      severe metabolic imbalances leading to a loss of fat stores in many animal
      species, a phenomenon known as the wasting syndrome. In this paper, we report
      that TCDD treatment at very low doses (0.03-1 micrograms/kg, single
      intraperitoneal injection) causes a profound reduction of glucose uptake by
      guinea pig adipose tissue, pancreas and brain. This effect of TCDD is dose
      dependent, with a dose as small as 0.03 micrograms/kg resulting in a significant
      decrease. In adipose tissue, the decrease begins within 6 h of treatment and
      persists at least 28 days. The Vmax of glucose transport was decreased by TCDD
      treatment, whereas the Km was unchanged. Liver behaves oppositely to adipose
      tissue. At early stages of treatment (6-12 h) glucose uptake was depressed, while
      at later stages (24-96 h) it was increased. In situ (explant tissue culture)
      treatment with TCDD yields similar trends as in vivo studies for glucose uptake
      in all three tissues. In adipose tissue culture TCDD starts reducing glucose
      uptake after 30 minutes. The inhibitory potencies of three dioxin congeners on
      adipose glucose transporting activities follows the same order of their
      toxicities in vivo. TCDD's effect on glucose transport is sensitive to
      cytochalasin B, a specific inhibitor of glucose transporter proteins. Based on
      these observations and the importance of glucose transporters to cellular energy
      maintenance, we conclude that at least in guinea pigs the reduction of glucose
      transporters in various tissues is one of the major causes for TCDD-induced
      wasting syndrome, which is so prominent in this species.

PMID- 1400291
TI  - Exon/intron structure of the human alpha 3(IV) gene encompassing the Goodpasture
      antigen (alpha 3(IV)NC1). Identification of a potentially antigenic region at the
      triple helix/NC1 domain junction.
AB  - The Goodpasture antigen has been identified as the non-collagenous (NC1) domain
      of alpha 3(IV), a novel collagen IV chain (Saus, J., Wieslander, J., Langeveld,
      J., Quinones, S., and Hudson, B.G. (1988) J. Biol. Chem. 263, 13374-13380). In
      the present study, the exon/intron structure and sequence for 285 amino acids of
      human alpha 3(IV), comprising 53 amino acids of the triple-helical domain and the
      complete NC1 domain (232 amino acids), were determined. Based on the comparison
      of the amino acid sequences of the alpha 1(IV), alpha 2(IV), alpha 3(IV), and
      alpha 5(IV) NC1 domains, a phylogenetic tree was constructed which indicates that
      alpha 2(IV) was the first chain to evolve, followed by alpha 3(IV), and then by
      alpha 1(IV) and alpha 5(IV). The exon/intron structure of these domains is
      consistent with this evolution model. In addition, it appears that alpha 3(IV)
      changed most after diverging from the parental gene. Analysis of its primary
      structure reveals that, at the junction between the triple-helical and NC1
      domains, there exists a previously unrecognized, highly hydrophilic region
      (GLKGKRGDSGSPATWTTR) which is unique to the human alpha 3(IV) chain, containing a
      cell adhesion motif (RGD) as an integral part of a sequence (KRGDSGSP) conforming
      to a number of protein kinase recognition sites. Based on primary structure data,
      we outline new aspects to be explored concerning the molecular basis of collagen
      IV function and Goodpasture syndrome.

PMID- 1400293
TI  - Enantiomeric selectivity of carbovir transport.
AB  - Carbovir (9-[4 alpha-(hydroxymethyl)cyclopent-2-ene-1 alpha-yl]guanine) (CBV) is
      a carbocyclic analogue of 2',3'-dideoxyguanosine that exhibits potent and
      selective in vitro activity against human immunodeficiency virus. Antiviral
      activity is associated with only the (-)-enantiomer. The transport
      characteristics of both (-)-CBV and (+)-CBV were investigated in human
      erythrocytes at 37 degrees C using a papaverine-stop assay. The influx of both
      enantiomers appeared saturable and was inhibited greater than 90% by a
      combination of adenine (a low Km permeant of the nucleobase carrier) and dilazep
      (a potent inhibitor of nucleoside transport). The influx of (-)-CBV and (+)-CBV
      proceeded primarily via the nucleobase carrier with Vmax (picomoles/second/5
      microliters of cells)/Km (millimolar) values of 17/0.12 and 140/1.9,
      respectively. To a lesser extent, the influx of (-)-CBV and (+)-CBV also occurred
      via the nucleoside transporter. Although both compounds exhibited a similar low
      affinity for this latter carrier (Km approximately 2 mM), the Vmax for (-)-CBV
      influx was approximately 4-fold higher than the Vmax for (+)-CBV influx. We
      conclude that both CBV enantiomers enter human erythrocytes by two transporters
      that are enantiomerically selective.

PMID- 1400294
TI  - Identification of molecular aggregates containing glycoproteins III, J, K
      (carboxypeptidase H), and H (Kex2-related proteases) in the soluble and membrane
      fractions of adrenal medullary chromaffin granules.
AB  - An investigation of the molecular properties of glycoprotein III has shown this
      to be a major component of molecular aggregates present in the membrane and
      soluble fractions of secretory vesicles from bovine adrenal medulla. These
      aggregates also contain components identified as glycoproteins H, J, and K which
      are molecular forms of Kex2-related proteases (glycoprotein H) and
      carboxypeptidase H (glycoprotein components J and K) and which have functions
      concerned with the processing of prohormones. A number of experiments indicated
      that these glycoproteins were associated. These components were
      coimmunoprecipitated from the soluble and membrane fractions of chromaffin
      granules. Purification of soluble glycoprotein III using wheat germ agglutinin
      Sepharose resulted in the recovery of similar proportions of glycoproteins H, J,
      and K and gel filtration of the eluted material in combination with
      immunoprecipitation revealed the presence of heteroaggregates containing all of
      the glycoproteins. Similar results were obtained following octylglucoside
      solubilization of chromaffin granule membranes. Glycoprotein components III, H,
      J, and K were also found to have identical distributions following fractionation
      of chromaffin granule membranes with Triton X-114. It was concluded that the
      aggregates seen in the soluble fraction reflect an association of these
      components in the chromaffin granule membrane. This raises the possibility that
      these interactions are important for the targetting of these glycoproteins to
      secretory granules.

PMID- 1400295
TI  - DNA melting within stable closed complexes at the Escherichia coli rrnB P1
      promoter.
AB  - Several transcription complexes are shown to form on the E. coli ribosomal rrnB
      P1 promoter in vitro. These include two closed complexes that are sensitive to
      heparin attack, and one open complex. The closed complexes are unusual in that
      they are both highly specific and stable, properties associated with the atypical
      DNA sequence of this promoter. The effector ppGpp does not prevent closed complex
      formation but does reduce the level of open complexes that form.

PMID- 1400296
TI  - Tissue-specific DNaseI hypersensitivity regions are located in the 5'-region of
      the rat preproenkephalin gene.
AB  - Extracellular stimuli affecting mechanisms of transcriptional control of the
      preproenkephalin gene link stimulus-secretion-synthesis coupling to transmitter
      phenotypic expression. In order to define distal and proximal genomic regions
      that might participate in transcriptionally active protein-DNA interactions,
      DNaseI hypersensitivity assays were conducted. Four DNaseI-hypersensitive regions
      were identified at -3000, -2500, -1800, and -200 base pairs (bp) relative to the
      somatic start site. The appearance of a site over the proximal promoter/enhancer
      region (-200 bp) is of interest since we and others have published a detailed
      footprint and functional analysis of this region using rat tissues. While liver
      (which does not express proenkephalin mRNA) displays essentially no
      hypersensitivity here, adrenal gland preparations show a strong signal and
      striatal tissue a significantly weaker signal. Cholinergic induction of
      proenkephalin mRNA was not associated with a change in hypersensitivity pattern.
      These data suggest that chromatin structure may have an influence on
      preproenkephalin transcriptional control and that cholinergic-inducible cis
      acting DNA elements may reside within subdomains of at least these four
      hypersensitivity sites. Understanding the basis of this open chromatin structure
      should aid in identifying genomic mechanisms involved in tissue-specific
      expression and suggest avenues of future study.

PMID- 1400297
TI  - Role of cadmium in activating nuclear protein kinase C and the enzyme binding to
      nuclear protein.
AB  - Specific effects of cadmium on nuclear protein kinase C activity were found with
      3T3/10T1/2 mouse fibroblast and rat liver nuclei. Treatment of the mouse
      fibroblasts in culture with 12-O-tetradecanoylphorbol-13-acetate resulted in the
      stimulation of nuclear protein kinase C activity in a "fixed" pool which is
      defined by its resistance to chelator extraction, whereas the chelator
      extractable enzyme activity, defined as the "labile" pool was unaffected. Cadmium
      was found to potentiate the effect of the phorbol ester, directed specifically to
      nuclei, since the particulate protein kinase C activity was not changed under
      similar treatment. In a reconstituted system consisting of rat liver nuclei and
      rat brain protein kinase C, cadmium stimulated the binding of the enzyme to a 105
      kDa nuclear protein. The binding of a 105-kDa protein to protein kinase C is
      attributed strictly due to the cadmium effect, whereas a 50-kDa protein binding
      to protein kinase C was only enhanced by cadmium. We propose a mechanistic model,
      where cadmium substitutes zinc in the regulatory domain of protein kinase C
      rendering the putative protein-protein binding site exposed.

PMID- 1400298
TI  - Molecular cloning of PEC-60 and expression of its mRNA and peptide in the
      gastrointestinal tract and immune system.
AB  - The peptide PEC-60, structurally related to the pancreatic secretory trypsin
      inhibitor, inhibits glucose-induced insulin secretion. Here we report on the
      structure of a cDNA clone from pig duodenum encoding PEC-60. The cDNA encodes a
      86-amino acid long precursor protein containing a 26-amino acid signal sequence,
      implying that the mature PEC-60 peptide is secreted from cells. Analysis of
      porcine duodenum demonstrated a high expression of a 0.6-kilobase long PEC-60
      mRNA in this tissue, as well as the presence of strong PEC-60-like
      immunoreactivity in the cytoplasm of the majority of the goblet cells of the
      epithelium. High levels of PEC-60 mRNA were also found in the bone marrow and the
      peripheral blood and moderate levels in the spleen. A strong PEC-60-like
      immunoreactivity was localized in the monocytes of peripheral blood.
      Radioimmunoassay revealed high levels of pig PEC-60-like immunoreactivity in pig
      plasma suggesting that the PEC-60 peptide is efficiently released from cells.
      These findings imply that the gastrointestinal peptide PEC-60 is formed, stored,
      and secreted from monocytes present within the bone marrow and in the peripheral
      blood, indicating a role of the PEC-60 peptide in the immune system in addition
      to its function as a gastrointestinal peptide.

PMID- 1400299
TI  - Assembly and expression of an intrinsic factor IX activator complex on the
      surface of cultured human endothelial cells.
AB  - Endothelial cells expose specific receptors for blood clotting factors and, upon
      perturbation, can initiate and propagate the reactions of the extrinsic pathway
      of blood coagulation leading to fibrin formation on the cell surface. The
      existence of an intrinsic mechanism of Factor IX activation on cultured human
      umbilical vein cells (HUVECs) was investigated by studies of the interaction
      between HUVECs and two proteins of the contact activation system, the cofactor
      high molecular weight kininogen (H-kininogen) and the zymogen Factor XI. In the
      presence of zinc ions (10-300 microM), 125I-labeled H-kininogen bound to HUVECs
      in a time-dependent, reversible, and saturable manner, with calcium ions exerting
      an inhibitory effect on the zinc-dependent binding. Analysis of the binding data
      by the LIGAND computer program indicated that HUVECs, in the presence of 2 mM
      CaCl2 and 100 microM ZnCl2 at 37 degrees C, bound 1.14 x 10(7) H-kininogen
      molecules per cell with an apparent dissociation constant of 55 nM. HUVEC-bound H
      kininogen functions as the cell surface receptor for both 125I-labeled Factor XI
      and 125I-labeled Factor XIa, since HUVECs cultured in contact factor-depleted
      serum do not detectably bind either the zymogen or the enzyme in the absence of H
      kininogen and zinc ions. In the presence of saturating concentrations of H
      kininogen, 2 mM CaCl2 and 100 microM ZnCl2, the binding of 125I-labeled Factor XI
      and Factor XIa to HUVECs was time-dependent, reversible, and saturable, with
      apparent dissociation constants of 4.5 and 1.5 nM, respectively. HUVEC-bound
      complexes of H-kininogen and Factor XI generated Factor XIa activity only after
      the addition of purified Factor XIIa, and cell-bound Factor XIa in turn activated
      Factor IX, as documented by a 3H-labeled activation peptide release assay for 3H
      Factor IX activation. The results indicate that cultured HUVECs provide a surface
      for the assembly and expression of an intrinsic Factor IX activator complex that
      may participate in the initiation of blood coagulation at sites of vascular
      injury.

PMID- 1400300
TI  - Acyl-CoA esters modulate intracellular Ca2+ handling by permeabilized clonal
      pancreatic beta-cells.
AB  - Cytosolic free Ca2+ rises in pancreatic beta-cells in response to glucose
      stimulation and is part of the coupling to insulin secretion. This study
      evaluates a possible role for cytosolic long chain acyl-CoA esters in modulating
      Ca2+ handling by clonal beta-cells (HIT). Intact cells incubated with 20 microM
      free palmitic acid exhibited a 40% decrease in basal cytosolic free Ca2+. In
      contrast, acyl-CoA esters, up to a chain length of 16, but not the corresponding
      fatty acids, significantly lowered the Ca2+ set point maintained by cells
      permeabilized with saponin. The maximum response to the various acyl-CoA esters
      increased with increasing chain length, with no differences in the half-maximally
      effective concentration of 0.5 microM. Long chain acyl-CoA esters caused a 40-50%
      increase in 45Ca2+ influx into a non-mitochondrial pool in the permeabilized HIT
      cells, consistent with a stimulatory effect on the endoplasmic reticulum Ca(2+)
      ATPase activity, but did not affect inositol 1,4,5-trisphosphate-induced Ca(2+)
      efflux. Thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase
      activity, blocked the decrease in the Ca2+ set point caused by acyl-CoA esters.
      The ability of acyl-CoA esters to lower the Ca2+ set point depended on the
      ATP/ADP ratio (or free ADP); the Ca2+ set point was lowered by 36 +/- 3.6% at an
      ATP/ADP ratio of 90 and by 14 +/- 1.9% at an ATP/ADP ratio of 7. Depletion of
      cellular protein kinase C did not prevent the acyl-CoA-induced lowering of the
      Ca2+ set point. These findings suggest that the increases in long chain acyl-CoA
      esters may play a role in restoring cytosolic free Ca2+ through activation of
      Ca(2+)-ATPases.

PMID- 1400301
TI  - Epoxyeicosatrienoic acids inhibit Ca2+ entry into platelets stimulated by
      thapsigargin and thrombin.
AB  - The epoxyeicosatrienoic acids derived from the cytochrome P-450 pathway of
      arachidonic acid metabolism have a unique platelet antiaggregatory profile. This
      prompted us to examine their influence on cellular Ca2+ mobilization. 14,15-cis
      Epoxyeicosatrienoic acid and related compounds inhibited the rise in cytosolic
      Ca2+ following agonist stimulation of platelets by thapsigargin, a receptor
      independent agonist, and thrombin, a receptor-dependent agonist. The
      epoxyeicosatrienoic acids selectively inhibited the entry of Ca2+ from the
      exterior of the platelets but did not alter Ca2+ discharge from intracellular
      pools. The magnitude of inhibition by 14,15-cis-epoxyeicosatrienoic acid was
      proportional to the rate of Ca2+ entry. 14,15-cis-Epoxyeicosatrienoic acid also
      inhibited the rate of influx of Mn2+, a cation which enters platelets via
      pathways similar to Ca2+. The magnitude of inhibition was proportional to the
      rate of Mn2+ entry, suggesting that epoxyeicosatrienoic acids act on divalent
      cation channels in a fashion which depends on the state of opening of the
      channel. Selective inhibition of Ca2+ entry into platelets may account for the
      antiaggregatory effects of the epoxyeicosatrienoic acids. We are unaware of other
      endogenous compounds exhibiting this property, suggesting that
      epoxyeicosatrienoic acids may be useful to probe agonist-stimulated Ca2+
      mobilization in nonexcitable cells.

PMID- 1400302
TI  - Site-directed mutagenesis of glutathione S-transferase YaYa. Important roles of
      tyrosine 9 and aspartic acid 101 in catalysis.
AB  - The roles of tyrosine 9 and aspartic acid 101 in the catalytic mechanism of rat
      glutathione S-transferase YaYa were studied by site-directed mutagenesis.
      Replacement of tyrosine 9 with phenylalanine (Y9F), threonine (Y9T), histidine
      (Y9H), or valine (Y9V) resulted in mutant enzymes with less than 5% catalytic
      activity of the wild type enzymes. Kinetic studies with purified Y9F and Y9T
      mutants demonstrated poor catalytic efficiencies which were largely due to a
      drastic decrease in kcat. The estimated pK alpha values of the sulfhydryl group
      of glutathione bound to Y9F and Y9T mutant enzymes were 8.5 to 8.7, similar to
      the chemical reaction, in contrast to the estimated pK alpha value of 6.7 to 6.8
      for the glutathione enzyme complex of wild type glutathione S-transferase. These
      results indicate that tyrosine 9 is directly responsible for the lowering of the
      pKa of the sulfhydryl group of glutathione, presumably due to the stabilization
      of the thiolate anion through hydrogen bonding with the hydroxyl group of
      tyrosine. To examine the role of aspartic acid in the binding of glutathione to
      YaYa, 4 conserved aspartic acid residues at positions 61, 93, 101, and 157 were
      changed to glutamic acid and asparagine. All mutant enzymes retained either full
      or partial activity except D157N, which was virtually inactive. Kinetic studies
      with four mutant enzymes (D93E, D93N, D101E, and D101N) indicate that only D101N
      exhibited a 5-fold increase in Km toward glutathione. Also, the binding of this
      mutant to the affinity column was greatly reduced. These results demonstrate that
      aspartic acid 101 plays an important role in glutathione interaction to YaYa. The
      role of aspartic acid 157 in catalysis remains to be determined.

PMID- 1400303
TI  - Mechanism and stereochemistry in the sequential enzymatic saturation of the two
      double bonds in cholesta-4,6-dien-3-one.
AB  - The mechanism and stereochemistry in connection with enzymatic conversion of
      cholesta-4,6-dien-3-one into cholestanol was studied. Rat and mouse liver
      microsomes are able to catalyze NADPH-dependent sequential saturation of the two
      double bonds. Evidence was obtained that the saturation of the delta 6-double
      bond includes transfer of a hydride ion from the B-side of the cofactor to the 7
      position of the steroid (mainly 7 beta-position), followed by addition of a
      proton to the 6 alpha-position (mainly trans addition). The saturation of the
      delta 4-double bond includes transfer of a hydride ion from the B-side of the
      cofactor to the 5 alpha-position of the steroid followed by addition of a proton
      to the 4 beta-position (trans addition). The reduction of the 3-oxo group was
      found to involve transfer of a hydride ion from the B-side of the cofactor NADPH
      to the 3 alpha-position of the steroid. The results are in accord with the
      contention that the enzymatic saturation of the two double bonds involves a
      polarization of the 3-oxo group making C-7 electrophilic and C-6 nucleophilic in
      connection with the saturation of the delta 6-double bond and C-5 electrophilic
      and C-4 nucleophilic in connection with the saturation of the delta 4-double
      bond.

PMID- 1400304
TI  - Pulmonary surfactant secretion is regulated by the physical state of
      extracellular phosphatidylcholine.
AB  - Pulmonary alveolar type II cells synthesize, secrete, and recycle the components
      of pulmonary surfactant. In this report we present evidence that
      dipalmitoylphosphatidylcholine is a potent inhibitor of surfactant lipid
      secretion by type II cells. Monoenoic and dienoic phosphatidylcholines with fatty
      acids of 16 or 18 carbons are ineffective as inhibitors of surfactant lipid
      secretion. In contrast, disaturated phosphatidylcholines, with either symmetric
      or asymmetric pairs of fatty acids of 14, 16, or 18 carbons, exhibit inhibition
      of surfactant secretion that correlates extremely well with the phase transition
      temperature (Tc) of the phospholipid. The inhibitory activity of
      dipalmitoylphosphatidylcholine is not dependent upon lipid stereochemistry. N
      Methylated derivatives of dipalmitoylphosphatidylethanolamine are significantly
      less effective than phosphatidylcholine as inhibitors. Phosphatidylcholines below
      their phase transition temperature are inhibitors of surfactant secretion,
      whereas those above their phase transition temperature are either ineffective or
      weakly inhibitory. The phase transition dependence of inhibition is observed when
      type II cells are incubated at 37 degrees C with different species of
      phosphatidylcholine. In addition, if type II cells are stimulated to secrete at
      different temperatures the efficacy of a given phospholipid as an inhibitor is
      dependent on its relationship to Tc (i.e. dipalmitoylphosphatidylcholine with a
      Tc of 41 degrees C significantly inhibits secretion at 37 degrees C but not at 42
      degrees C). Inhibition of surfactant secretion by dipalmitoylphosphatidylcholine
      is abrogated when it is incorporated into the same liposome with
      dioleoylphosphatidylcholine as a 50:50 mixture. In contrast, the simultaneous
      addition of two separate populations of liposomes, one composed of
      dipalmitoylphosphatidylcholine and the other composed of
      dioleoylphosphatidylcholine, does not significantly alter the inhibitory activity
      found with dipalmitoylphosphatidylcholine alone. These data provide compelling
      evidence that the physical state of phosphatidylcholine can regulate surfactant
      secretion from alveolar type II cells and suggest a unique mechanism for
      regulating exocytosis in the alveolus of the lung.

PMID- 1400305
TI  - Expression in Escherichia coli, purification, and reactivation of the recombinant
      Erwinia uredovora phytoene desaturase.
AB  - A plasmid has been constructed by cloning the complete crtI gene encoding
      phytoene desaturase from Erwinia uredovora behind the lac Z promoter of pUC18
      resulting in a reading frame for the full polypeptide with additional 9 amino
      acids at the N terminus. This plasmid mediated the overexpression of phytoene
      desaturase in transformed Escherichia coli. The overexpressed enzyme was
      sequestrated into inclusion bodies requiring urea treatment for solubilization.
      Purification to homogeneity was subsequently performed on a DEAE-cellulose column
      and by SDS-polyacrylamide gel electrophoresis. The purification scheme allowed
      the isolation of 5.3 mg of homogeneous desaturase protein from 100 ml of E. coli
      cell suspension. On SDS-polyacrylamide gel electrophoresis an apparent molecular
      mass of 56.2 kDa was determined. An antiserum raised against phytoene desaturase
      cross-reacted with the expressed protein and was employed to monitor the
      isolation steps. Upon removal of urea, desaturase activity was restored. The
      isolated desaturase catalyzed the conversion of 15-cis-phytoene to trans-lycopene
      as well as to bisdehydrolycopene. FAD was involved in desaturation, whereas NAD
      and NADP were inhibitory. This is the first time that a membrane-integrated
      carotenogenic enzyme has been purified and finally obtained in an active state.

PMID- 1400306
TI  - Characterization of the interaction between the heavy and light chains of bovine
      factor Va.
AB  - Bovine factor Va has been previously been shown to consist of heavy (M(r) =
      94,000) and light chains (M(r) = 81,000), that interact in a manner dependent
      upon the presence of either calcium or manganese ions. In an attempt to
      understand the mechanism of subunit interaction we have studied the effects of
      temperature and ions on factor Va stability. The rates of formation of factor Va
      from isolated chains and dissociation were temperature-dependent with an energy
      of activation of 6.2 and 1.3 kcal mol-1, respectively. The yield of factor Va
      from isolated chains was inversely related to the amount of time the chains were
      incubated at 4 degrees C. Incubation of individual chains revealed that the heavy
      chain is cold-labile, an effect that is reversible. Manganese ion was observed to
      prevent the conversion to the inactive form. High salt tends to stabilize the two
      chain structure of factor Va, but is inhibitory to its formation from isolated
      chains. High concentrations of either manganese or calcium ions also inhibited
      reconstitution of activity. The light chain, in particular, was sensitive to the
      presence of manganese or calcium ion. Heavy chain that had been cleaved by
      activated protein C had a weakened interaction with the light chain, and the
      resulting complex had no procoagulant activity. Cooling of the heavy chain to 4
      degrees C enhanced its intrinsic fluorescence. Manganese ion prevented some of
      this enhancement. The heavy chain fluorescence returned to the room temperature
      value with a half-life of approximately 10 min. In the presence of manganese ion
      relaxation was accelerated. The intrinsic fluorescence of activated protein C
      cleaved heavy chain was not increased when the temperature was decreased. These
      data suggest that the heavy chain can exist in two forms. Elevated temperature
      converts it to a form that can bind ions and have a productive interaction with
      the light chain. However, conditions that prevent the heavy chain from combining
      with the light chain also stabilize the two subunit structure, suggesting that
      the high affinity of the complex is due to conformational changes that occur
      after chain interaction.

PMID- 1400307
TI  - Secondary structure and folding of a functional chloroplast precursor protein.
AB  - Ferredoxin is a chloroplast stroma protein which is cytosolically synthesized as
      a precursor with an amino-terminal extension called the transit sequence that is
      needed for the post-translational uptake by the chloroplast. To characterize the
      secondary and tertiary structure elements, the full precursor, the holo- and apo-
      (without iron-sulfur cluster) forms of the mature protein, and the chemically
      synthesized transit peptide were obtained and analyzed separately. Circular
      dichroism, tryptophan fluorescence quenching, and protease accessibility
      experiments indicate that the precursor has a low content of defined secondary
      structure and resembles unfolded proteins; these properties are due to both the
      mature part and the transit sequence. This result provides an explanation for the
      lack of cytosolic factor requirement of this protein for import. In an import
      competition assay, the isolated transit peptide had an affinity for the
      chloroplasts comparable to the full precursor. Interestingly and of possible
      importance to the import process, the transit peptide has conformational
      flexibility as it adopts alternative secondary structures in different
      environments.

PMID- 1400308
TI  - Increased exposure of hydrophobic surface in molten globule state of alpha
      lactalbumin. Fluorescence and hydrophobic photolabeling studies.
AB  - The involvement of molten globule state as a distinct intermediate in the
      denaturation process in proteins is well documented. However, the structural
      characterization of such an intermediate is far from complete. We have, using
      fluorescence and fluorescence quenching, studied the molten globule state of
      bovine alpha-lactalbumin. Unlike the native state, where all the 4 tryptophans
      are buried in the protein, 2 tryptophans are exposed in the molten globule state.
      Using the hydrophobic photoactivable reagent [3H]diazofluorene, we observe an
      increased hydrophobic exposure in the molten globule state. These structural
      characteristics conform to the current views on the molten globule state, i.e. it
      has similar secondary structure but a poorly defined tertiary structure. Our
      fluorescence studies indicate the involvement of a premolten globule state in the
      native to molten globule state transition. This premolten globule state exists at
      pH 5.0 and has a very compact structure involving increased hydrophobic
      interactions in the protein interior. These results are also supported by
      circular dichroism studies.

PMID- 1400309
TI  - Mucin biosynthesis revisited. The enzymatic transfer of Gal in beta 1,3 linkage
      to the GalNAc moiety of the core structure R1-GlcNAc beta 1,6GalNAc alpha-O-R2.
AB  - Synthetic glycosides containing the core, -Glc-NAc beta 1,6GalNAc alpha-, acted
      as acceptors for beta-galactosyltransferase of human ovarian tumor. A significant
      amount of Gal was transferred from UDP-Gal (100 nmol) to the alpha
      benzylglycoside of LacNAc beta 1,6GalNAc (LGBn) (25.1 nmol of Gal) and the alpha
      ortho-nitrophenylglycosides of LacNAc beta 1,6GalNAc (22.0 nmol of Gal), GlcNAc
      beta 1,6GalNAc (15.5 nmol of Gal), and Fuc alpha 1,3GlcNAc beta 1,6GalNAc (25.9
      nmol of Gal); LacNAc beta 1,6(Gal beta 1,3)GalNAc alpha-O-Bn (where Bn is benzyl)
      was almost inactive (only 1.2 nmol of Gal), indicating the Gal transfer to the
      alpha-GalNAc moiety. The product from LGBn was isolated in microgram quantities
      and identified by fast atom bombardment mass spectrometry as LacNAc beta 1,6(Gal
      beta 1,3)GalNAc alpha-O-Bn. The alpha GalNAc:beta 1,3Gal transferase was present
      in high concentration in ovarian tumor tissue (ovarian cancer serum----1.4;
      ascitic fluid----0.9; tumor----17.4). Asialo Cowper's gland mucin (ACGM) at 5
      mg/ml reaction mixture inhibited the transfer of Gal to LGBn (25.2 and 53.4%
      respectively for 2 and 18 h incubation at 37 degrees C); inhibition by LGBn was
      13.4 and 24.5%, respectively. In contrast to the inhibition by ACGM (25.2-31.6%),
      there was substantial increase (13.4-35.7%) in the inhibition by LGBn, when the
      incubation for 2 h at 37 degrees C was continued for 40 h at 4 degrees C,
      indicating the high affinity of LGBn for the enzyme at lower temp. Km for LGBn in
      presence of ACGM was 7.6 mM and in absence, 2.7 mM; Km for ACGM (M(r) 200,000) in
      presence of LGBn was 16.1 microM and Ki for ACGM (as the inhibitor) was 41.7
      microM. In comparison with two normal ovarian tissues, the enzyme was found to be
      low (55-67%) in three ovarian tumors and high (146-260%) in two ovarian and one
      uterus tumors, as measured with ACGM; the synthetic acceptors showed similar
      activities. The enzyme had nearly the same extent of activity in the pH range 6
      8. Fuc alpha 1,3GlcNAc beta 1,6GalNAc alpha-O-ONP had the highest affinity for
      the enzyme. The present study demonstrates the feasibility of beta 1,3Gal
      attachment on alpha GalNAc, which has already been substituted by beta 1,6GlcNAc,
      then elongated by beta 1,4Gal and also terminated by alpha 1,3Fuc.

PMID- 1400311
TI  - The complete amino acid sequence of yam (Dioscorea japonica) chitinase. A newly
      identified acidic class I chitinase.
AB  - The complete amino acid sequence of acidic chitinase from yam (Dioscorea
      japonica) aerial tubers was determined. The protein is composed of a single
      polypeptide chain of 250 amino acid residues and has a calculated molecular mass
      of 27,890 Da. There is an NH2-terminal domain, a hinge region, and a main
      structure, typical for class I chitinases (Shinshi, H., Neuhaus, J.-M., Ryals,
      J., and Meins, F., Jr. (1990) Plant Mol. Biol. 14, 357-368). We have obtained the
      first evidence for an acidic class I chitinase. Comparison with sequences of
      other class I chitinases revealed approximately 40% sequence similarity, a value
      lower than that for other class I chitinases (70-80%). We assume that there is a
      local conformational change in the molecule; cysteine residues that probably form
      disulfide bonds are completely conserved, with the exception of Cys-178. The
      difference in structure between this chitinase and other basic class I chitinases
      suggests that acidic and basic isoforms should be grouped into subclasses; this
      protein is an ethylene- or a pathogen-independent chitinase produced by a gene
      that is inherent in the tuber.

PMID- 1400310
TI  - Identification of an activating transcription factor (ATF) binding site in the
      human transforming growth factor-beta 2 promoter.
AB  - Transforming growth factor TGF-beta 2 is encoded by multiple mRNA transcripts of
      5.8, 5.1, 4.0, 3.8, and 2.8 kilobase pairs (kb) that are expressed in various
      human and monkey cells. Northern blot analysis using genomic fragments of DNA was
      used to demonstrate that some of this size heterogeneity is due to differences in
      the length of the 5'-untranslated region. Probes that were colinear with the
      first 600 nucleotides of the 5'-untranslated region detected only the 5.8-, 4.0-,
      and 3.8-kb transcripts. In order to identify DNA elements that regulate the
      transcription of these mRNA transcripts, deletion constructs of 5'-flanking DNA
      were ligated to the coding region for chloramphenicol acetyltransferase (CAT) and
      analyzed for promoter activity in several cell lines. Sequences responsible for
      putative enhancer and silencer regions were identified between -778 and -40
      relative to the transcription initiation site. Addition of a cyclic AMP
      responsive element/activating transcription factor-like element at -74 resulted
      in a 5-10-fold increase in CAT activity over that expressed with a construct that
      contained only the TATA box. This increase in CAT activity was suppressed by the
      addition of DNA sequences between -257 and -187, whereas sequences between -778
      and -257 stimulated CAT activity. Point mutations within the ATF binding site at 
      74 resulted in a marked decrease in CAT expression. Cotransfection with ATF-1 or
      ATF-2 expression plasmids resulted in both dose-dependent stimulatory and
      inhibitory activities that were cell type-dependent. These studies identify
      multiple transcription initiation sites for TGF-beta 2 and demonstrate that
      transcription from one of these promoters is dependent upon an ATF binding site
      located 5' of the TATA box.

PMID- 1400312
TI  - Selective inhibition of mutant Ha-ras mRNA expression by antisense
      oligonucleotides.
AB  - A biological reporter gene assay was employed to determine the crucial parameters
      for maximizing selective targeting of a Ha-ras codon 12 point mutation (G----T)
      using phosphorothioate antisense oligonucleotides. We have tested a series of
      oligonucleotides ranging in length between 5 and 25 bases, each centered around
      the codon 12 point mutation. Our results indicate that selective targeting of
      this point mutation can be achieved with phosphorothioate antisense
      oligonucleotides, but this selectivity is critically dependent upon
      oligonucleotide length and concentration. The maximum selectivity observed in
      antisense experiments, 5-fold for a 17-base oligonucleotide, was closely
      predicted by a simple thermodynamic model that relates the fraction of mutant to
      wild type target bound as a function of oligonucleotide concentration and
      affinity. These results suggest thermodynamic analysis of oligonucleotide/target
      interactions is useful in predicting the specificity that can be achieved by an
      antisense oligonucleotide targeted to a single base point mutation.

PMID- 1400313
TI  - Inhibition of mitogen-induced c-fos expression in melanoma cells by retinoic acid
      involves the serum response element.
AB  - To investigate the mechanism(s) by which all-transretinoic acid (RA) inhibits
      cell growth, we studied its effect on the expression of c-fos and c-jun in B16
      melanoma cells. RA differentially inhibited proto-oncogene induction by mitogens,
      such as phorbol 12-myristate 13-acetate and serum. Suppression of c-fos was
      achieved with doses of RA as low as 10(-10) M and required pretreatment of cells
      with RA for a minimum of 2 h. In contrast, inhibition of c-jun required
      pretreatment for greater than 16 h with at least 10(-8) M RA and coincided with
      the observed decrease in cell growth. RA blocked c-fos induction by inhibiting
      transcription. This inhibition of transcription occurs through the serum response
      element (SRE), since the SRE alone was sufficient to confer down-regulation by RA
      to a minimal c-fos promoter construct. Thus, the SRE plays a critical role in the
      suppression of c-fos transcription by RA.

PMID- 1400314
TI  - Characterization of the tryptophanase operon of Proteus vulgaris. Cloning,
      nucleotide sequence, amino acid homology, and in vitro synthesis of the leader
      peptide and regulatory analysis.
AB  - The tryptophanase (tna) operon of Proteus vulgaris was cloned and characterized
      and found to be organized similarly to the tna operon of Escherichia coli. Both
      operons contain two major structural genes, tnaA and tnaB, that encode
      tryptophanase and a tryptophan permease, respectively. tnaA of P. vulgaris is
      preceded by a transcribed leader region, encoding a 34-residue leader peptide,
      TnaC, that contains a single tryptophan residue. The tnaC coding region also has
      a boxA-like sequence. Regulatory studies performed in P. vulgaris, and with a
      plasmid carrying the P. vulgaris tna operon in E. coli, established that
      expression of the Proteus operon was induced by tryptophan and was subject to
      catabolite repression. Site-directed mutagenesis studies established that
      translation of the tnaC coding region was essential for induction. Synthesis of
      the P. vulgaris leader peptide was demonstrated in an in vitro coupled
      transcription-translation system. Interestingly, the 5 amino acid residues of the
      TnaC peptide surrounding the sole tryptophan residue are identical in P. vulgaris
      and E. coli. We conclude that the tna operon of P. vulgaris is also regulated by
      tryptophan-induced transcription antitermination. Homology of tryptophanase and
      tryptophan permease of P. vulgaris to related proteins from other species is
      described.

PMID- 1400315
TI  - A novel CoA-independent transacetylase produces the ethanolamine plasmalogen and
      acyl analogs of platelet-activating factor (PAF) with PAF as the acetate donor in
      HL-60 cells.
AB  - In this study, we demonstrate the presence of a unique membrane-associated
      transacetylase that transfers the acetate group from platelet-activating factor
      (PAF) to lysoplasmalogen (in the presence of EDTA and sodium acetate) with the
      formation of 1-alk-1-enyl-2-acetyl-sn-glycero-3-phosphoethanolamine (alk-1
      enylacetyl-GPE). The identity of alk-1-enylacetyl-GPE was confirmed by acid
      hydrolysis, phospholipases A2 or C treatment and derivatization by
      fluorodinitrobenzene. The transacetylase has no requirement for Ca2+, Mg2+, or
      CoA and a broad pH optimum (7.0-8.0) with Km values of 12.0 microM for PAF and
      106.4 microM for lysoplasmalogens. The enzyme activity from the isolated membrane
      fraction is not changed when whole cells are supplemented with 20:4, induced to
      differentiate into granulocytes, or treated with ionophore A23187. Radyllyso-sn
      glycero-3-phosphocholine (GPC), radyllyso-GPE, acyllyso-sn-glycero-3
      phosphoserine (GPS), acyllyso-sn-glycero-3-phosphoinositol (GPI), alkyllyso-sn
      glycero-3-phosphate (GP), acyllyso-GP, or cis-9-octadecen-1-ol can also serve as
      acetate acceptors, whereas alkylglycerol, acylglycerol, or cholesterol are
      inactive. Differences in substrate acceptor specificity, sensitivity toward
      phenylmethylsulfonyl fluoride, and response to temperature suggest that the CoA
      independent transacetylase and the CoA-independent transacylase that transfers
      long-chain acyl moieties are two separate enzymes. With intact differentiated HL
      60 cells, [3H]acetate from [3H]PAF can be incorporated into alk-1-enylacetyl-GPE
      in the presence of ionophore A23187, but not in its absence. Moreover,
      phospholipase A2 inhibitors (p-bromophenacyl bromide and mepacrine) block the
      transacetylation process in whole cell system. These results indicate the
      production of alk-1-enyllyso-GPE is a rate-limiting factor for the subsequent
      transacetylation step during cell activation. We conclude that the transacetylase
      may participate in the biosynthesis of ethanolamine plasmalogen and acyl analogs
      of PAF, in vivo, fine-tuning of PAF biological responses, and cross-talk between
      de novo and remodeling pathways of PAF biosynthesis.

PMID- 1400316
TI  - Expression of mature bovine H-protein of the glycine cleavage system in
      Escherichia coli and in vitro lipoylation of the apoform.
AB  - H-protein, a component of the glycine cleavage system with lipoic acid as a
      prosthetic group, was expressed in Escherichia coli using a T7 RNA polymerase
      plasmid expression system. After induction with 25 microM isopropyl-beta-D
      thiogalactopyranoside, bacteria harboring the recombinant plasmid expressed
      mature bovine H-protein as a soluble form at a level of about 10% of the total
      bacterial protein. Little of the H-protein was lipoylated in E. coli cultured
      without added lipoate, but when the cells were cultured in medium supplemented
      with 30 microM lipoate, about 10% of the recombinant protein expressed was the
      correctly lipoylated active form, 10% was an inactive aberrantly modified form,
      presumably with an octanoyl group, and the remaining 80% was the unlipoylated
      apoform. Each of the three forms was purified to homogeneity and shown to have
      the same NH2-terminal amino acid sequence as that of native bovine H-protein. The
      specific activity of the lipoylated form of H-protein expressed was consistent
      with that of H-protein purified from bovine liver. The purified recombinant apo-H
      protein was lipoylated and consequently activated in vitro with lipoyl-AMP as a
      lipoyl donor by lipoyltransferase purified 150-fold from bovine liver
      mitochondria. The lipoylation was dependent on lipoyl-AMP, apo-H-protein, and
      lipoyltransferase. The partially purified lipoyltransferase had no lipoate
      activating activity. These results provide the first evidence that in mammals two
      consecutive reactions are required for the attachment of lipoic acid to the
      acceptor protein: the activation of lipoic acid to lipoyl-AMP catalyzed by
      lipoate-activating enzyme and the transfer of the lipoyl group to an N epsilon
      amino group of a lysine residue to apoprotein by lipoyl-AMP:N epsilon-lysine
      lipoyltransferase.

PMID- 1400317
TI  - Site-directed mutagenesis of the active site cysteine in Klebsiella aerogenes
      urease.
AB  - Cysteine 319 in the large subunit of Klebsiella aerogenes urease was identified
      as an essential catalytic residue based on chemical modification studies (Todd,
      M.J., and Hausinger, R.P. (1991) J. Biol. Chem. 266, 24327-24331). Through site
      directed mutagenesis, this cysteine has been changed independently to alanine,
      serine, aspartate, and tyrosine. None of these mutations (C319A, C319S, C319D,
      and C319Y, respectively) affected the size or level of synthesis of the urease
      subunits as monitored by polyacrylamide gel electrophoresis. The wild type enzyme
      and each of the mutant proteins was purified and their properties were compared.
      The C319Y protein possessed no detectable activity, while activity was reduced in
      C319A, C319S, and C319D to 48, 4.5, and 0.03% of wild type levels under normal
      assay conditions. All of the active mutants had a small increase in Km when
      compared to the wild type value. The active mutants displayed a greatly reduced
      sensitivity to inactivation by iodoacetamide in comparison to the wild type
      enzyme, confirming our previous assignment of the essential cysteine to this
      residue based on active site peptide mapping. In contrast to the wild type
      enzyme, inactivation of the mutant proteins was not affected by the presence of
      the competitive inhibitor phosphate, suggesting that the remaining slow rate of
      iodoacetamide inactivation is due to modification away from the active site. The
      pH dependence of urease activity was substantially altered in the active mutants
      with C319S and C319D showing a pH optimum near 5.2, and C319A near 6.7, compared
      to the pH 7.75 optimum of wild type urease. These data are consistent with Cys
      319 facilitating catalysis at neutral and basic pH values by participating as a
      general acid.

PMID- 1400318
TI  - Activity and dimerization of human immunodeficiency virus protease as a function
      of solvent composition and enzyme concentration.
AB  - The activity of human immunodeficiency virus 1 (HIV-1) protease has been examined
      as a function of solvent composition, incubation time, and enzyme concentration
      at 37 degrees C in the pH 4.5-5.5 range. Glycerol and dimethyl sulfoxide inhibit
      the enzyme, while polyethylene glycol and bovine serum albumin activate the
      enzyme. When incubated at a concentration of 50-200 nM, the activity of the
      protease decreases irreversibly with an apparent first-order rate constant of 4-9
      x 10(-3) min-1. The presence of 0.1% (w/v) polyethylene glycol or bovine serum
      albumin in the reaction buffer dramatically stabilizes enzyme activity. In the
      absence of prolonged incubation of the enzyme at submicromolar concentration, the
      specific activity of HIV-1 protease in buffers of either high or low ionic
      strength is constant over the enzyme concentration range of 0.25-5 nM, indicating
      that dissociation of the dimeric protease, if occurring, can only be governed by
      a picomolar dissociation constant. Similarly, the variation of the specific
      activity of HIV-2 protease over the enzyme concentration of 4-85 nM is consistent
      only with a dimer dissociation constant of less than 10 nM. We conclude that: 1)
      the assumption of a nondissociating HIV-1 protease is a valid one for kinetic
      studies of tight-binding inhibitors where nanomolar concentrations of the enzymes
      are employed; 2) stock protease solutions of submicromolar concentration in the
      absence of activity-stabilizing compounds may lead to erroneous kinetic data and
      complicate mechanistic interpretations.

PMID- 1400319
TI  - Post-translational modifications of p21rho proteins.
AB  - Post-translational modifications of the ras proteins, which are required for
      plasma membrane localization and biological function of the proteins, have been
      shown to include prenylation and carboxymethylation at the carboxyl terminal
      cysteine residue of the cysteine-aliphatic amino acid-aliphatic amino acid-any
      amino acid (CAAX) box. In addition, p21Ha-ras and p21N-ras, but not p21K-ras (B),
      are palmitoylated. The three mammalian rho proteins (A, B, and C) are also
      members of the ras superfamily but have distinct biological activities and
      different intracellular distributions from p21ras. Analysis showed all three rho
      proteins are modified by a COOH-terminal carboxymethylation similar to p21ras,
      whereas p21rhoC labeled with [3H]mevalonic acid in vivo revealed the presence of
      a C20 prenoid, similar to that already described for p21rhoA. However, in vivo
      and in vitro studies of p21rhoB showed this protein to be modified by both C15
      and C20 prenoids. Mutation of C193 in the CAAX box abolished prenylation, whereas
      mutation of the adjacent C192 resulted in a significant reduction in the amount
      of the C20, but not C15 prenoid, recovered from p21rhoB. In vivo labeling studies
      with [3H]palmitic acid and mutational analysis showed that both cysteine residues
      at 189 and 192 upstream of the CAAX box in p21rhoB are sites for palmitoylation.
      We conclude that there are different populations of post-translationally modified
      p21rhoB in the cell and that the sequence specificity for geranylgeranyl- and
      farnesyltransferases may be more complicated than previously proposed.

PMID- 1400320
TI  - A murein hydrolase is the specific target of bulgecin in Escherichia coli.
AB  - A deletion in the structural gene for the soluble lytic transglycosylase, the
      predominant murein hydrolase in the soluble fraction of Escherichia coli, has
      been constructed. The mutant grows normally but exhibits increased sensitivity
      toward mecillinam, a beta-lactam specific for penicillin-binding protein 2. In
      the presence of furazlocillin or other beta-lactams with a specificity for
      penicillin-binding protein 3 which normally cause filamentation, bulges were
      formed prior to rapid bacteriolysis. Similar morphological alterations are known
      to develop in wild type E. coli cells when furazlocillin is combined with
      bulgecin, an antibiotic of unusual glucosaminyl structure. It turned out that
      bulgecin specifically inhibits the Sl-transglycosylase in a noncompetitive
      manner. Since bulgecin shows some structural analogy to the murein subunits we
      postulate that the soluble lytic transglycosylase, in addition to its active
      site, has a recognition site for specific murein structures. The possibility of
      an allosteric modulation of the activity of the enzyme by changes in the
      structure of the murein sacculus is discussed.

PMID- 1400321
TI  - Interleukin-1-mediated PGE2 production and sphingomyelin metabolism. Evidence for
      the regulation of cyclooxygenase gene expression by sphingosine and ceramide.
AB  - We recently demonstrated that sphingosine enhances interleukin-1 beta (IL-1)
      mediated prostaglandin E2 (PGE2) production in human dermal fibroblasts (Ballou,
      L. R., Barker, S. C., Postlethwaite, A. E., and Kang, A. H. (1990) J. Immunol.
      145, 4245-4251). Because sphingosine and ceramide are interconvertable, we
      extended previous studies by treating cells with C2-ceramide (C2-cer), a membrane
      soluble analogue of ceramide, and found that C2-cer stimulates IL-1-mediated PGE2
      production to the same degree as sphingosine. In an effort to elucidate the
      mechanistic basis by which sphingosine and C2-cer affect PGE2 production, we
      examined the effect of these molecules on the expression of genes encoding
      cyclooxygenase (EC 1.14.99.1, Cox) and phospholipase A2 (EC 3.1.1.4, PLA2), the
      rate-limiting enzymes in PGE2 biosynthesis. We found that sphingosine and C2-cer
      treatment resulted in an 8-fold induction of Cox mRNA within 1-2 h which declined
      thereafter; concomitant changes in Cox protein were also observed. In contrast,
      expression of phospholipase A2 remained unaltered. We also found that IL-1
      mediated PGE2 production was dramatically enhanced in cells treated
      simultaneously with sphingomyelinase which led us to directly test the effect of
      IL-1 on sphingomyelin turnover. IL-1 treatment induced the hydrolysis of a
      significant fraction of prelabeled sphingomyelin which was accompanied by
      increased levels of intracellular ceramide. Taken together, our results suggest
      that enhanced Cox expression may account for the observed enhancement of IL-1
      mediated PGE2 production by sphingosine and C2-cer. These data also suggest that
      endogenous sphingomyelin metabolites, generated in response to IL-1, may play an
      important role in IL-1 signal transduction.

PMID- 1400322
TI  - Mechanism of free fatty acid transfer from rat heart fatty acid-binding protein
      to phospholipid membranes. Evidence for a collisional process.
AB  - Fatty acid binding proteins (FABP) are a family of low molecular weight proteins
      found in many tissues that actively utilize free fatty acids (ffa). FABP would be
      expected to have a particularly important role in the heart, where over 80% of
      energy requirements are derived from oxidation of long chain fatty acids. The
      precise physiological function of heart FABP (H-FABP) has not been definitively
      identified, although it is thought to play a role in intracellular ffa transport.
      To examine the possible role of H-FABP in cardiac myocyte transfer of ffa, we
      examined the transfer of fluorescent anthroyloxy ffa (AOffa) from H-FABP to model
      phospholipid membranes, using a resonance energy transfer assay. In contrast to
      previous observations of ffa transfer from liver FABP and from membranes,
      transfer from H-FABP to membranes appears to occur by a different mechanism. AO
      palmitate (16:0) transfer was 1.5-fold slower than AO-stearate (18:0) transfer,
      and mono-unsaturation did not affect the transfer rate. The AOffa transfer rate
      from H-FABP increased with increasing ionic strength and decreased slightly
      between pH 7 and 9. These results suggest that the rate of ffa transfer from H
      FABP to membranes is independent of the ffa aqueous solubility. Thermodynamic
      analysis showed that the free energy of activation for the ffa transfer process
      arises primarily from an enthalpic component, with only a small entropic
      contribution, again suggesting the lack of an aqueous phase route of ffa
      delivery. Finally, the ffa transfer rate was found to be directly dependent on
      the concentration of acceptor membranes. These data therefore suggest that
      transfer of AOffa from H-FABP to membranes may occur via collisional interactions
      between the protein and membranes.

PMID- 1400323
TI  - Solid-state NMR assessment of enzyme active center structure under nonaqueous
      conditions.
AB  - By using solid-state NMR spectroscopy, the integrity of the active center of
      alpha-chymotrypsin was investigated under a variety of nonaqueous conditions.
      Specifically, 13C cross-polarization/magic angle spinning NMR was used to analyze
      the ability of alpha-chymotrypsin to stabilize a transition state intermediate
      analog after freezing, drying, and addition of organic solvents (both anhydrous
      and hydrated) to the resultant powder. Lyophilization disrupted 42 +/- 5% of the
      active centers; it was determined that this occurred during drying, as opposed to
      freezing. Seven anhydrous solvents caused 0-50% additional disruption, which
      occurred immediately on addition of the solvent to the enzyme powder. The extent
      of structural integrity loss correlated with the solvent hydrophobicity,
      indicating that further dehydration, i.e. stripping of water retained by the
      enzyme during lyophilization, was the cause. Enzyme samples prepared with
      lyoprotecting additives, sucrose and ammonium sulfate, exhibited varying degrees
      of stabilization against the drying step of lyophilization. Moreover, when
      hydrophilic anhydrous solvents, which had the highest propensity to strip bound
      water, were added to the resultant enzyme powders, no additional damage occurred.

PMID- 1400324
TI  - Substrate specificities of rat liver peroxisomal acyl-CoA oxidases: palmitoyl-CoA
      oxidase (inducible acyl-CoA oxidase), pristanoyl-CoA oxidase (non-inducible acyl
      CoA oxidase), and trihydroxycoprostanoyl-CoA oxidase.
AB  - Rat liver peroxisomes contain three acyl-CoA oxidases:palmitoyl-CoA oxidase,
      pristanoyl-CoA oxidase, and trihydroxycoprostanoyl-CoA oxidase. The three
      oxidases were separated by anion-exchange chromatography of a partially purified
      oxidase preparation, and the column eluate was analyzed for oxidase activity with
      different acyl-CoAs. Short chain mono (hexanoyl-) and dicarboxylyl (glutaryl-)
      CoAs and prostaglandin E2-CoA were oxidized exclusively by palmitoyl-CoA oxidase.
      Long chain mono (palmitoyl-) and dicarboxylyl (hexadecanedioyl-)-CoAs were
      oxidized by palmitoyl-CoA oxidase and pristanoyl-CoA oxidase, the former enzyme
      catalyzing approximately 70% of the total eluate activity. The very long chain
      lignoceroyl-CoA was also oxidized by palmitoyl-CoA oxidase and pristanoyl-CoA
      oxidase, the latter enzyme catalyzing approximately 65% of the total eluate
      activity. Long chain 2-methyl branched acyl-CoAs (2-methylpalmitoyl-CoA and
      pristanoyl-CoA) were oxidized for approximately 90% by pristanoyl-CoA oxidase,
      the remaining activity being catalyzed by trihydroxycoprostanoyl-CoA oxidase. The
      short chain 2-methylhexanoyl-CoA was oxidized by trihydroxycoprostanoyl-CoA
      oxidase and pristanoyl-CoA oxidase (approximately 60 and 40%, respectively, of
      the total eluate activity). Trihydroxycoprostanoyl-CoA was oxidized exclusively
      by trihydroxycoprostanoyl-CoA oxidase. No oxidase activity was found with
      isovaleryl-CoA and isobutyryl-CoA. Substrate dependences of palmitoyl-CoA oxidase
      and pristanoyl-CoA oxidase were very similar when assayed with the same (common)
      substrate. Since the two oxidases were purified to a similar extent and with a
      similar yield, the contribution of each enzyme to substrate oxidation in the
      column eluate probably reflects its contribution in the intact liver.

PMID- 1400325
TI  - Association of pp60src with Triton X-100-insoluble residue in human blood
      platelets requires platelet aggregation and actin polymerization.
AB  - Protein-tyrosine phosphorylation during platelet activation is inhibited under
      conditions that inhibit platelet binding of fibrinogen and aggregation. We
      suggested that pp60src, a major platelet tyrosine kinase, or its protein
      substrates might become associated with the cytoskeleton upon platelet
      stimulation, and that this might be related to aggregation. By Western blotting
      with an anti-Src monoclonal antibody, we found time-dependent association of
      pp60src with the cytoskeleton (10,000 x g Triton X-100-insoluble matrix) but not
      the "membrane" cytoskeleton (100,000 x g Triton X-100-insoluble matrix) in
      platelets activated by U46619 (PGH2 analog). Cytoskeletal association and
      platelet aggregation were inhibited by the peptide Arg-Gly-Asp-Ser (RGDS) (but
      not by Arg-Gly-Glu-Ser (RGES)), by 10E5 antibody against glycoprotein (Gp)
      IIb/IIIa, and by EGTA. U46619-induced association of pp60src with cytoskeleton
      but not secretion or aggregation was inhibited by cytochalasin D (2 microM). Both
      cytochalasin D and RGDS inhibited "slow" tyrosine phosphorylation of platelet
      proteins. Association of pp60src with cytoskeleton induced by U46619 or ADP was
      not blocked by aspirin. Aspirin blocked epinephrine-induced association of
      pp60src with the cytoskeleton during a second phase of aggregation when an
      initial phase had occurred without shape change or secretion. Association of
      GpIIb/IIIa with the cytoskeleton also accompanied platelet aggregation, shape
      change, and actin polymerization; this was shown with anti-GpIIb and anti-GpIIIa
      antibodies. Association of pp60src and GpIIb/IIIa with the cytoskeleton and slow
      tyrosine phosphorylation are related phenomena.

PMID- 1400326
TI  - Identification and partial purification of a large, variant form of type XII
      collagen.
AB  - A large, alternate form of type XII collagen has been identified in cultures of
      the human epidermoid cell line WISH. This form, designated XIIA, is comprised of
      alpha chains that are approximately 90 kDa larger than the 220-kDa alpha chain
      previously characterized in extracts of fetal chicken and bovine tissues. Results
      from both collagenase digestion and rotary shadow analysis of partially purified
      material show that the increase is due to a larger NC3 domain. While both the
      large (XIIA) and the small (XIIB) forms of type XII collagen are identified in
      pulse-chase radiolabeling of fetal bovine skin explant culture, they are not
      related in a precursor-product fashion. Inhibition studies with alpha, alpha'
      dipyridyl indicate that proper folding of the collagen helix is required for
      complete assembly and secretion of type XIIA in WISH cell culture. The 310-kDa
      alpha 1A chain is likely to represent the bovine equivalent of a second
      translation product, estimated to be 340 kDa, predicted from analysis of one
      complete chick cDNA sequence. Additionally, the amino-terminal amino acid
      sequence of the 220-kDa bovine alpha 1B chain was determined. This sequence is
      very near a potential alternate splice site predicted from analysis of chicken
      type XII cDNA.

PMID- 1400327
TI  - Characterization of collagen types XII and XIV from fetal bovine cartilage.
AB  - The structurally related type XII-like collagen molecules TL-A and TL-B were
      recently identified in fetal bovine epiphyseal cartilage and subsequently shown
      to be collagen types XII and XIV, respectively. By indirect immunofluorescent
      staining of cartilage using monoclonal antibodies to the NC3 domains of each
      molecule, it was shown that type XII collagen was present predominantly around
      cartilage canals, the articular surface, subperichondrial margins, and the
      perichondrium, was less so in the remaining cartilage matrix, and was absent from
      the growth plate region. In the permanent cartilage of trachea, type XII stained
      somewhat more intensely in the margins beneath the loose connective tissue. Type
      XIV collagen localized more uniformly throughout the articular cartilage and was
      also absent from the growth plate region, whereas in tracheal cartilage, its
      distribution was similar to type XII. We have characterized the structure of
      these cartilage molecules and compared them with those from fetal bovine skin.
      Extraction of cartilage with 1 M NaCl and differential NaCl precipitation yields
      a fraction enriched for these two collagens. Analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and immunoblotting with monoclonal antibodies
      to the large amino-terminal non-triple-helical domain, NC3, revealed the presence
      in cartilage of two forms of type XII collagen: type XIIB, the molecule
      previously identified in chick and bovine tissues, and type XIIA, a much larger
      form equivalent to the molecule recently identified in WISH-transformed
      epithelial cell culture medium (Lunstrum, G. P., McDonough, A. M., Marinkovich,
      M. P., Keene, D. R., Morris, N. P., and Burgeson, R. E. (1992) J. Biol. Chem.
      267, 20087-20092). Digestion with bacterial collagenase shows that the increased
      mass is present in the NC3A domain. Additional purification by velocity
      sedimentation and observation of rotary-shadowed images demonstrates molecules
      with extended non-triple-helical arms approximately 80 nm in length analogous to
      the WISH cell molecules. Electrophoretic mobilities of bands corresponding to
      type XIIA, but not type XIIB, are sensitive to chondroitinase ABC, indicating
      that type XIIA is a chondroitin sulfate proteoglycan and that modification occurs
      predominantly within the NC3A domain distal to NC3B. Neither type XIIB from skin
      nor type XIIA from WISH cells are chondroitinase-sensitive. By similar analysis,
      a portion of the type XIV collagen chains in cartilage was also sensitive to
      chondroitinase digestion. Chondroitin sulfate is apparently not located on its
      NC3 domain. As in skin, collagen types XII and XIV have subtly different
      distributions within cartilage and type XII may have a tissue-specific structure.

PMID- 1400328
TI  - Copper transfer and activation of the Streptomyces apotyrosinase are mediated
      through a complex formation between apotyrosinase and its trans-activator MelC1.
AB  - The melanin operon (melC) of Streptomyces antibioticus is composed of two genes
      that encode MelC1 and MelC2 proteins. MelC1 has been suggested as a trans
      activator which can facilitate the incorporation of copper into the apotyrosinase
      (MelC2) (Lee, Y.-H. W., Chen, B.-F., Wu, S.-Y., Leu, W.-M., Lin, J.-J., Chen, C.
      W., and Lo, S. J. (1988) Gene (Amst.) 65, 71-81). However, the molecular
      mechanism of the trans-activation or copper-transfer process mediated through
      MelC1 to MelC2 is not clear yet. In this study, we found apotyrosinase in both
      the extracellular fraction and cell extract from cells grown in copper-deficient
      medium. Using gel-filtration and immunoaffinity chromatographies, we demonstrated
      that apotyrosinase (MelC2) formed a stable complex with MelC1 in the intra- and
      extracellular fractions. Furthermore, addition of copper ion to the complex
      generated tyrosinase activity. The MelC1-MelC2 complex was purified to near
      homogeneity by DE52 and phenyl-agarose chromatographies. In conjunction with fast
      protein liquid gel filtration chromatography and NH2-terminal sequencing
      analysis, the results indicated that the stoichiometric ratio of MelC1 and MelC2
      in the purified complex was 1:1. Essentially no copper was found in the complex.
      Addition of copper ion to the purified complex resulted in incorporation of
      approximately 2 molecules of copper ion and the mature active tyrosinase was
      gradually released from the complex. Taken together, these results demonstrate
      that the molecular mechanism of activation of Streptomyces apotyrosinase by its
      trans-activator MelC1 is initially mediated via a binary complex formation
      between these two proteins, followed by incorporation of copper ion. This
      activation mechanism accounts for the essential role of MelC1 in the expression
      of melanin operon.

PMID- 1400329
TI  - Secretion of the Streptomyces tyrosinase is mediated through its trans-activator
      protein, MelC1.
AB  - The tyrosinase of Streptomyces antibioticus is encoded by the second open reading
      frame, melC2 of the melanin operon (melC). The upstream open reading frame melC1
      specifies a 146-amino acid protein with a typical NH2-terminal signal-peptide
      characteristic of a secretory protein. The MelC1 protein is involved in the
      transfer of copper ion to apotyrosinase MelC2 via binary complex formation (Lee,
      Y.-H. W., Chen, B.-F., Wu, S.-Y., Leu, W.-M., Lin, J.-J., Chen, C. W., and Lo, S.
      J. (1988) Gene (Amst.) 65, 71-81; Chen, L.-Y., Leu, W.-M., Wang, K.-T., and Lee,
      Y.-H.W. (1992) J. Biol. Chem. 267, 20100-20107). To investigate whether the
      export of tyrosinase is also dependent on MelC1, a mutational study of its signal
      peptide sequence was performed. Four different mutants were obtained. Mutation at
      the positively charged region (mutant M-6LE, Arg6-Arg7----Leu6-Glu7) or the
      hydrophobic region (mutant M-16D, Val16----Asp16) led to Mel- phenotypes. These
      lesions caused a severe 7-10-fold reduction of the export of both the MelC1 and
      MelC2 proteins and a concomitant accumulation of the two proteins in the
      cytosolic fraction. The cell-associated tyrosinase activity in M-6LE but not in
      the M-16D mutant was dramatically reduced to 4% of the activity found in the wild
      type strain, suggesting that the basic NH2 terminus of MelC1 is also important
      for the trans-activation function of this protein. Nevertheless, the defects on
      the trans-activation and/or secretory functions of MelC1 in mutants M-6LE and M
      16D are not due to the impairment of the formation of the MelC1.MelC2 complex.
      The translation of melanin operon genes in these two mutants also decreased. In
      contrast, the tyrosinase activity and the secretion of MelC2 were not affected if
      the mutations occurred at the putative cleavage site of the signal peptidase
      (e.g. mutant M-29SM, Arg29-Ala30----Ser29-Met30 or mutant 29-SMG, Arg29-Ala30
      Asp31----Ser29-Med30-Gly31+ ++). Additionally, tyrosinase activity and its export
      were abolished in a MelC1-negative mutant, M-950. Taken together, these results
      demonstrate that a functional MelC1 is essential for tyrosinase secretion and
      activity. Furthermore, the results suggest that like other secretory proteins,
      basic and hydrophobic residues in the MelC1 signal sequence are an important
      feature of the signal-peptide and play a pivotal role in the secretion of both
      the MelC1 and MelC2 proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1400330
TI  - Fibulin binds to itself and to the carboxyl-terminal heparin-binding region of
      fibronectin.
AB  - Fibulin is a recently described extracellular matrix (ECM) and plasma
      glycoprotein (Argraves, W. S., Tran, H., Burgess, W. H., and Dickerson, K. (1990)
      J. Cell Biol. 111, 3155-3164). In this report, ligand affinity chromatography and
      solid-phase binding analyses were performed to determine which ECM protein(s)
      interact with fibulin. Fibulin-Sepharose bound two polypeptides of 240 and 100
      kDa from the culture medium of metabolically radiolabeled fibroblasts. These two
      proteins were identified as fibronectin (FN) and fibulin, respectively, based on
      their electrophoretic behavior and reactivity with monoclonal antibodies.
      Consistent with the findings of affinity chromatography, fibulin bound to
      surfaces coated with FN (either plasma or cellular form) or fibulin but not with
      other ECM proteins, such as laminin, merosin, and types I and IV collagen. The
      binding of fibulin to solid-phase FN was estimated to have a Kd of 139 nM,
      whereas the Kd for self-interaction was 322 nM. Evaluation of proteolytic
      fragments from all regions of FN allowed a fibulin-binding site to be localized
      within a 23-kDa heparin-binding fragment containing type III repeats 13-14.
      Heparin did not compete for the interaction between fibulin and FN, suggesting
      that the binding sites for fibulin and heparin are distinct.

PMID- 1400331
TI  - Missense mutations in exon 5 of the human lipoprotein lipase gene. Inactivation
      correlates with loss of dimerization.
AB  - Most missense mutations of the lipoprotein lipase (LPL) gene identified among LPL
      deficient subjects cluster in a segment of the sequence that encodes the
      catalytic triad as well as functional elements involved in the activation of the
      lipase at lipid-water interfaces. Consequently, loss of activity may result
      either from direct alterations of such functional elements or from less specific
      effects on protein folding and stability. This issue was addressed by examining
      biochemical properties of four such variants (A176T, G188E, G195E, and S244T) in
      a heterologous expression system (COS-1 cells). Variant G195E (GGA----GAA) was
      previously unreported. In all instances, inactive enzyme was recovered in medium,
      albeit at reduced levels. Cellular synthesis and extracellular degradation were
      similar to those for wild type, suggesting that reduced secretion resulted from
      increased intracellular degradation. When cell extracts were subjected to heparin
      Superose affinity chromatography followed by elution on a linear salt gradient,
      all variants exhibited a single, inactive, low affinity immunoreactive peak. By
      contrast, wild-type enzyme presented an additional, high affinity, active
      species, which we interpret as homodimeric enzyme. Substitution of the active
      site serine (S132A) led to loss of activity but maintenance of the high affinity
      species. When large amounts of the G188E variant were applied to the column,
      small but significant amounts of high affinity, active enzyme were recovered.
      Systematic substitutions at residue 188 showed that only glycine could
      accommodate structural constraints at this position. We conclude that the
      mutations examined did not impart lipase deficiency by affecting specific
      functional elements of the enzyme. Rather, they appear to affect protein folding
      and stability, and thereby formation and maintenance of subunit assembly.

PMID- 1400333
TI  - Constitutive expression of AP-1 transcription factors in the rat adrenal. Effects
      of nicotine.
AB  - The AP-1 proteins (c-fos and fos-related antigens and jun proteins) are
      transcription factors that are induced in most cells by various stimuli, but the
      expression of these proteins is low or undetectable in the basal state. Our data
      indicate that the rat adrenal gland contains a basally expressed elevated level
      of AP-1 proteins and mRNAs (40- and 35-kDa fos-related antigens, a 39-kDa c-jun
      protein, c-jun, junB, and junD mRNA), as well as high basal AP-1 DNA binding
      activity. Both the medulla and cortex contained equivalent levels of fos-related
      antigens and c-jun protein; however, the majority of AP-1 DNA binding was
      detected in the medulla. Handling of rats for several days prior to sacrifice
      failed to affect protein expression or binding; on the other hand, repeated
      injections of nicotine increased AP-1 DNA binding. A single nicotine injection 60
      min prior to removing the adrenals caused a significant reduction in AP-1 DNA
      binding without any detectable changes in AP-1 protein expression. Pretreatment
      of adrenal nuclear extracts with alkaline phosphatase prior to incubation with
      the AP-1 oligomer decreased binding activity. Thus, unlike most tissues where AP
      1 DNA binding activity is controlled by increased expression of AP-1 proteins,
      DNA binding in the rat adrenal gland appears to be controlled at the post
      translational level, possibly through dephosphorylation.

PMID- 1400334
TI  - Immunological characterization and intracellular localization of trans
      spliceosomal small nuclear ribonucleoproteins in Trypanosoma brucei.
AB  - Polyclonal antibodies were raised against purified protein components of the U2
      small nuclear ribonucleoprotein (snRNP) from Trypanosoma brucei. Through
      immunoblot and immunoprecipitation analyses three antisera were characterized
      that reacted specifically with U2 snRNP proteins of molecular weights 40,000
      (anti-40K) and 16,500 (anti-16.5K), and with each of four proteins of molecular
      weights 14,000, 12,500, 10,000, and 8,500 (anti-CP). Anti-40K antibodies
      specifically immunoprecipitated the U2 snRNP from trypanosomal extracts, whereas
      anti-CP antibodies recognized several snRNPs, including the SL RNP and the U2 and
      U4/U6 snRNPs; in addition, minor RNAs were detected, suggesting that a family of
      snRNPs with common or related protein components exists in trypanosomes. None of
      these antibodies cross-reacted significantly with total mammalian snRNP proteins,
      indicating that the trypanosomal snRNP proteins are immunologically distinct from
      their mammalian counterparts. Using immunofluorescence microscopy, the snRNP
      proteins exhibited a differential cellular distribution. Whereas the 40-kDa
      protein is localized exclusively in the nucleus, with the nucleolus being
      excluded, a fraction of the common proteins also resides in the cytoplasm.

PMID- 1400332
TI  - Evidence for participation of GTP-binding proteins in elicitation of the rapid
      oxidative burst in cultured soybean cells.
AB  - GTP-binding proteins have been shown to serve as second messengers in the
      transduction of hormone signals across animal cell plasma membranes. We present
      here three lines of evidence to demonstrate that GTP-binding proteins are also
      involved in the elicitation of the defense response of cultured soybean cells.
      First, the antigen-binding fragment (Fab) of an antibody that specifically
      recognizes GTP-binding proteins in plants and animals was delivered into soybean
      cells using a non-destructive biotin-mediated delivery technique developed
      previously. Internalization of this Fab enhanced up to 10-fold the rapid
      oxidative burst induced by elicitor molecules, whereas internalization of its
      heat-denatured counterpart or unrelated proteins had no effect. Because the
      antibody recognizes a protein of molecular mass approximately 45 kDa in soybean
      cell membranes that is protected from ADP-ribosylation by GTP gamma S (guanosine
      5'-O-(thiotriphosphate), we propose the 45-kDa GTP-binding protein is responsible
      for these effects. Second, mastoparan, a specific activator of GTP-binding
      proteins, was shown to induce the defense-related oxidative burst in the absence
      of elicitor stimulation, thus mimicking an activated receptor as it is thought to
      do in mammalian systems. Finally, but admittedly less convincing, the A subunit
      of cholera toxin, an activator of certain stimulatory GTP-binding proteins (Gs),
      was found to weakly enhance the conventional elicitor-induced oxidative burst.
      Taken together, these data argue for the involvement of GTP-binding proteins in
      elicitor signal transduction in soybean cells.

PMID- 1400335
TI  - Characterization of the role of lysine 110 of NADH-cytochrome b5 reductase in the
      binding and oxidation of NADH by site-directed mutagenesis.
AB  - An expression vector for bovine NADH-cytochrome b5 reductase was used for site
      directed mutagenesis of lysine 110, the residue previously implicated in NADH
      interactions with this flavoprotein. Replacement of this basic residue with an
      uncharged glutamine resulted in an increase of 3 orders of magnitude in the Km
      for NADH and a decrease in kcat of an order of magnitude, strongly implicating
      lysine 110 in both binding of NADH to the reductase and the orientation of the
      reduced nicotinamide group for rapid hydride ion transfer to the flavin.
      Substitution of lysine 110 by histidine, to provide a pH-sensitive positive
      charge at this position in the neutral pH range, exhibited only a moderate 25
      fold increase in Km and a normal kcat at pH 6.0, whereas at pH 8.5 the Km for
      NADH rose to 238 microM with a decrease of 45% over unmodified enzyme in the
      kcat. A similar pH sensitivity in the inhibition constant for adenosine
      diphosphate ribose, lacking only the nicotinamide moiety of NADH, emphasizes the
      crucial role of the positive charge at this locus and is consistent with charge
      pairing of lysine 110 with the pyrophosphate group of NADH or adenosine
      diphosphate ribose.

PMID- 1400336
TI  - Interactions between the catalytic centers and subunit interface of
      triosephosphate isomerase probed by refolding, active site modification, and
      subunit exchange.
AB  - The effects of unfolding, refolding, and hybridization of triosephosphate
      isomerase (TPI) subunits from different species and subunits which have been
      specifically modified at the active site have been examined. These effects have
      been evaluated in terms of changes in catalytic parameters, CD spectra, and
      susceptibility to denaturation. Dissociation followed by reassociation yields an
      active dimer but with increased Km, reduced kcat, and increased susceptibility to
      inactivation and unfolding in denaturants. These data suggest that while the
      general structure of the refolded dimer is similar to the native enzyme, its
      complete original structure is not restored. Covalent reaction of the active site
      Glu165 with the substrate analogue 3-chloroacetol phosphate (CAP) results in
      dimers with increased susceptibility to unfolding and inactivation by denaturants
      (i.e. the rates of inactivation and unfolding are (TPICAP)2 greater than (TPI
      TPICAP) greater than (TPI)2). These data point to the interactions between the
      catalytic center and the subunit interface. Subunits of TPI from different
      species, in spite of structural differences at the subunit interface, hybridized
      to active heterodimers. Subunit hybridization was random among monomers from
      different mammals, preferential between yeast and mammalian or avian monomers.
      Hybridization did not occur between avian and mammalian monomers under these
      conditions. These data provide information on the elements in the interface of
      the dimer and the relationship of the catalytic center with the subunit
      interface.

PMID- 1400337
TI  - Genetic dissection of the transcription cycle. A mutant RNA polymerase that
      cannot hold onto a promoter.
AB  - Deletion of 10 amino acids from a conserved motif in the beta subunit of
      Escherichia coli RNA polymerase (RNAP) leads to an interrupted transcription
      cycle and lethal phenotype. RNAP carrying the mutant subunit retains catalytic
      function and specificity of promoter recognition but is unable to efficiently
      hold onto DNA in the binary complex, resulting in a diminished initiation
      frequency. However, inefficient initiation by the mutant enzyme leads to
      processive and stable ternary elongating complex. Thus, the mutation dissects the
      traits of promoter selectivity, binary complex stability, and ternary complex
      processivity reflecting compartmentalization of function within the RNAP
      molecule.

PMID- 1400338
TI  - Tagetitoxin inhibition of RNA polymerase III transcription results from enhanced
      pausing at discrete sites and is template-dependent.
AB  - In yeast nuclear extracts, tagetitoxin inhibition of RNA polymerase III promoter
      directed single- and multiple-round transcription is characterized by pausing or
      stalling of the elongation complex at several discrete points on the template.
      Paused ternary complexes isolated from tagetitoxin-inhibited reactions can be
      elongated to produce full-length RNA. The distribution of "tagetitoxin-enhanced"
      pause sites is distinct for each of the class III genes we have examined. These
      tagetitoxin-enhanced pause sites may also be intrinsic pause sites for the
      elongation complex. Tagetitoxin inhibition of in vitro transcription of the yeast
      SUP4 and SUP6 tRNA(Tyr) genes demonstrates template dependence and indicates that
      inhibition may occur after UMP incorporation. Factor-independent transcription by
      purified yeast RNA polymerase III can also be inhibited by tagetitoxin, and the
      degree of inhibition is template-dependent. Tagetitoxin may be most effective as
      an inhibitor under conditions where polymerase III tends to pause on the
      template. We propose that differences in tagetitoxin inhibition among class III
      genes may reflect differences in the number of stability of these pause sites.

PMID- 1400339
TI  - Isolation and characterization of the rat liver actin N-acetylaminopeptidase.
AB  - Actins from most eukaryotes undergo a unique post-translational modification of
      the amino terminus called "processing." Processing consists of the removal of an
      amino-terminal Ac-Met or Ac-Cys to leave an acidic amino-terminal residue. We
      have previously demonstrated that this reaction is not catalyzed by the
      ribosomally associated methionine aminopeptidase or by other previously described
      acetylaminopeptidases. Here we present the isolation and characterization of the
      actin N-acetylaminopeptidase (ANAP) from rat liver. A five-step purification
      protocol achieves a 4100-fold purification of the enzyme with an overall 8%
      recovery of activity. ANAP is a 77-kDa monomer with a pI of 4.6. Using
      unprocessed yeast actin as a substrate, the Km of ANAP is 3.5 microM. Purified
      ANAP was used to generate a polyclonal antibody. The antibody has been used along
      with activity assays to demonstrate the presence of ANAP in a variety of rat
      tissues. Finally, evidence is presented that in mammals, ANAP may function with a
      second, as yet unpurified, component to process actin amino termini.

PMID- 1400340
TI  - Lipid interactions of the hemagglutinin HA2 NH2-terminal segment during influenza
      virus-induced membrane fusion.
AB  - Fusion of influenza viruses with target membranes is induced by acid and involves
      complex changes in the viral fusion protein hemagglutinin (HA) and in the contact
      sites between viruses and target membranes (Stegmann, T., White, J. M., and
      Helenius, A. (1990) EMBO J. 9, 4231-4241). At 0 degrees C, in a first,
      kinetically distinct step, target membranes irreversibly adhere to the viruses.
      Fusion itself starts only after a lag-phase of several minutes (X-31 strain
      viruses) or after raising the temperature (PR8/34 strain viruses). We now provide
      evidence that the initial conformational change resulting in virus-target
      membrane adhesion is restricted to a (minor) subpopulation of the HA molecules.
      These molecules become susceptible to bromelain digestion, and they could be
      labeled with the photoactivatable reagent [3H]PTPC/11, a nonexchangeable lipid
      present in the target lipid bilayer (Harter, C., Bachi, T., Semenza, G., and
      Brunner, J. (1988) Biochemistry 27, 1856-1864). Only the HA2 subunit was labeled,
      and analyses of 2-nitro-5-thio-cyanobenzoic acid fragments derived thereof
      indicate that the HA2 NH2-terminal segment (fusion peptide) inserted into the
      target membrane bilayer. When the temperature was raised to trigger fusion of
      PR8/34 viruses, labeling of HA2 increased by a factor of 130. Most (74%) of that
      label was incorporated into the COOH-terminal membrane anchor region, but there
      was also a strong increase (about 30-fold) of NH2-terminal fusion peptide
      labeling. This suggests that fusion is preceded., or accompanied, by further
      changes in HA which lead to additional extensive lipid insertions of HA2 fusion
      peptides.

PMID- 1400341
TI  - Differential regulation of the alpha 2 beta 1 and alpha IIb beta 3 integrin genes
      during megakaryocytic differentiation of pluripotential K562 cells.
AB  - Expression of the alpha 2 beta 1 and alpha IIb beta 3 integrin genes is
      differentially regulated during megakaryocytic differentiation of pluripotent
      K562 cells induced with phorbol 12,13-dibutyrate. Upon megakaryocytic
      differentiation, steady-state alpha 2 mRNA increased markedly from the
      undetectable level present in the uninduced cells. The level of beta 1 mRNA did
      not change. Expression of alpha IIb beta 3 is regulated differently. beta 3 mRNA
      was undetectable in uninduced cells but increased significantly following
      induction. alpha IIb mRNA was detectable at a low level prior to induction, but
      at an increased level following differentiation. Altered mRNA stability did not
      contribute to changes in mRNA levels. Nuclear run-off experiments revealed a 20
      fold increase in alpha 2 gene transcription upon megakaryocytic differentiation,
      but no change in transcription of the beta 1 gene. Transcription of both the
      alpha IIb and beta 3 genes increased 10- and 5-fold, respectively. Thus, the
      increase in alpha 2 beta 1 protein which accompanies the megakaryocytic
      differentiation of K562 cells is a consequence of the increased steady-state
      level of alpha 2 mRNA due to transcriptional activation of the alpha 2 gene. The
      long-lived beta 1 mRNA is not altered during differentiation. In contrast,
      increased alpha IIb beta 3 protein appears due to increased steady-state levels
      of both alpha IIb and beta 3 mRNAs that result from transcriptional activation of
      both integrin genes.

PMID- 1400342
TI  - Endothelial monocyte-activating polypeptide II. A novel tumor-derived polypeptide
      that activates host-response mechanisms.
AB  - An important means by which tumor cells influence the vasculature is through the
      production of soluble mediators altering vascular properties. A approximately 22
      kDa polypeptide was purified to homogeneity from conditioned medium of murine
      methylcholanthrene A (meth A) fibrosarcoma cells by ion-exchange chromatography
      and preparative sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS
      PAGE), based on its ability to induce tissue factor procoagulant activity in
      endothelial cells (ECs). The final product migrated as a broad band on reduced
      and nonreduced SDS-PAGE and had an unique amino-terminal sequence. This meth A
      derived polypeptide modulated EC coagulant properties through the induction of
      tissue factor, induced monocyte migration and tissue factor expression, and was
      also chemotactic for granulocytes. Injection of the polypeptide into mouse
      footpads resulted in an inflammatory response with tissue swelling and
      polymorphonuclear leukocyte infiltration. The ability of this mediator to
      activate ECs and monocytes has led us to name it EMAP II (endothelial monocyte
      activating polypeptide). EMAP II is distinct from a previously described
      approximately 40-kDa meth A-derived polypeptide termed EMAP I. Through its
      potential to activate host effector mechanisms, EMAP II could contribute to the
      biology of immunogenic tumors, such as the meth A fibrosarcoma.

PMID- 1400344
TI  - MAK3 encodes an N-acetyltransferase whose modification of the L-A gag NH2
      terminus is necessary for virus particle assembly.
AB  - The MAK3 gene is necessary for propagation of the L-A double-stranded RNA virus
      of Saccharomyces cerevisiae. MAK3 encodes a protein with substantial homology to
      the Escherichia coli rimI N-acetyltransferase that acetylates the NH2 terminus of
      ribosomal protein S18, and shares consensus sequences with a group of N
      acetyltransferases. The NH2 terminus of the viral major coat protein encoded by L
      A is normally blocked, but we find that it is unblocked in a mak3-1 mutant. L-A
      virus-encoded proteins produced from a cDNA clone of L-A can encapsidate the L-A
      (+)-strands in a wild-type host, but not in a mak3-1 mutant strain. The amount of
      major coat protein found in the particle fraction is reduced greater than 100
      fold, and the amount in the total cell extract is reduced 5-10-fold. A modified
      beta-galactosidase, having as its NH2-terminal the NH2-terminal 13 residues of
      the L-A-encoded major coat protein, is blocked in a wild-type host, but not in a
      mak3-1 host. We propose that MAK3 encodes an N-acetyltransferase whose
      modification of the L-A major coat protein NH2 terminus is essential for viral
      assembly, and that unassembled coat protein is unstable.

PMID- 1400343
TI  - Human autoantibodies as reagents to conserved Golgi components. Characterization
      of a peripheral, 230-kDa compartment-specific Golgi protein.
AB  - We have used a serum from a patient with Sjogren's syndrome containing high titer
      (100,000) anti-Golgi autoantibodies and lower titer (20,000) anti-nuclear
      autoantibodies to characterize the Golgi complex. The Sjogren's syndrome serum
      immunoprecipitated a number of components of molecular mass 35-230 kDa from
      detergent extracts of [35S]methionine-labeled HeLa cells; at high dilution, the
      serum precipitated one major 230-kDa component. Using the Sjogren's syndrome
      serum, cDNA clones encoding the Golgi autoantigen were isolated from a lambda
      gt11 HeLa cell cDNA library. Autoantibodies from the Sjogren's syndrome serum,
      affinity purified from a recombinant bacterial fusion protein generated from one
      of the cDNA clones, showed Golgi staining of human, mouse, and chicken cells by
      immunofluorescence. The purified autoantibodies immunoprecipitated and
      immunoblotted a 230-kDa component. A rabbit antiserum raised to the recombinant
      fusion protein specifically stained the Golgi complex by immunofluorescence and
      reacted with a 230-kDa protein by immunoprecipitation and immunoblotting. The 230
      kDa protein was recovered in both the 100,000 x g sedimentable and soluble
      fractions in cell lysates and in the aqueous phase of Triton X-114 extracts. The
      230-kDa autoantigen was dissociated from the Golgi complex by 15-min brefeldin A
      treatment, dissociation kinetics similar to that of mannosidase II. However,
      unlike mannosidase II, autoantigen staining was markedly reduced after drug
      treatment. Removal of brefeldin A resulted in reassociation of the autoantigen
      with the Golgi complex. The epitopes recognized by the affinity purified human
      and rabbit antibodies were ultrastructurally localized to the cytosolic face of
      one side of the Golgi stack, probably the trans-face. Taken together, the 230-kDa
      protein is a conserved, peripheral membrane component specifically associated
      with one Golgi compartment. We suggest that this peripheral Golgi protein may
      have a role in the compartment-specific structural organization of the Golgi or
      in sorting and transport of proteins.

PMID- 1400345
TI  - cDNA cloning and sequencing reveals human tear prealbumin to be a member of the
      lipophilic-ligand carrier protein superfamily.
AB  - The gene encoding human tear prealbumin, a major component of the protein
      fraction of tear fluid, was cloned from total cDNA of lacrimal gland by
      polymerase chain reaction using synthetic oligonucleotides derived from N
      terminal amino acid sequences of the purified protein. Sequence analysis and a
      computer-assisted homology search revealed this protein to be a member of the
      lipocalin superfamily, consisting of hydrophobic-ligand carriers. The deduced
      amino acid sequence of tear prealbumin shares 58% identity with von Ebner's gland
      protein from rat, which is supposed to be involved in taste reception. In
      addition, significant homology has also been found with other members of the
      lipocalins, e.g. with beta-lactoglobulin. The predicted secondary structure of
      tear prealbumin resembles that of beta-lactoglobulin in the number and positions
      of nine beta-sheets and one alpha-helix at the C-terminal part of the protein,
      thus indicating a three-dimensional structure similar to beta-lactoglobulin.
      Protein sequencing revealed that the observed electrophoretic heterogeneity of
      tear prealbumin is due to subtle differences at the N terminus of the protein.
      The function of tear prealbumin as a lipophilic carrier was further supported by
      the fact that it binds [3H]retinol in vitro. Although this protein was originally
      described to be tear-specific, a tear prealbumin-specific antiserum also reacted
      with proteins of human saliva, sweat, and nasal mucus.

PMID- 1400346
TI  - Equal inhibition of HIV replication by stereoisomers of phosphatidyl
      azidothymidine. Lack of stereospecificity of lysosomal phospholipase A1.
AB  - Glycerol-1-P and glycerol-3-P stereoisomers of
      dipalmitoylphosphatidylazidothymidine were synthesized and found to have equal
      antiretroviral activity in HIV-infected HT4-6C cells. It was anticipated that the
      glycerol-1-P isomer would be less active because of slow metabolic conversion by
      cellular phospholipases A and C, but the antiretroviral results suggested that
      the human cell line (HT4-6C) may have phospholipases capable of hydrolyzing 2,3
      dipalmitoyl-sn-glycerol-1-phospho-5'-azidothymidine (AZT). To evaluate this
      possibility, we purified lysosomal phospholipase A1, an enzyme known to play a
      major role in cellular phospholipid catabolism. This enzyme rapidly hydrolyzed
      both the sn-1 and sn-3 isomers of dipalmitoylphosphatidyl-AZT. We synthesized sn
      2,3-dipalmitoyl-glycero-1-phosphocholine and found that it is also hydrolyzed
      readily by lysosomal phospholipase A1 although the Vmax, 59 mumol mg-1 h-1, is
      slightly lower than that of the sn-1,2-dipalmitoyl-glycero-3-phosphocholine, 89
      mumol mg-1 h-1. In conclusion, our studies show that sn-2,3-dipalmitoyl-glycerol
      1-phospho-AZT is equal in antiviral activity to sn-1,2-dipalmitoyl-glycero-3
      phospho-AZT in HIV-infected HT4-6C cells. This surprising result is due in part
      to the lack of stereospecificity of lysosomal phospholipase A1.

PMID- 1400347
TI  - Biphasic activation of two mitogen-activated protein kinases during the cell
      cycle in mammalian cells.
AB  - We studied mitogen-activated protein kinase (MAPK) activities during the cell
      cycle of Chinese hamster ovary (CHO) cells using site-specific antibodies against
      extracellular signal-regulated kinase-1, a 44-kDa MAPK (Boulton, T.G.,
      Yancopoulos, G.D., Gregory, J.S., Slauer, C., Moomaw, C., Hsu, J., and Cobb, M.H.
      (1990) Science 249, 64-67). These antibodies detected two distinct MAPKs (44- and
      42-kDa MAPKs) in CHO cells. CHO cells were arrested at metaphase in the M phase
      by treatment with nocodazole, and activities of MAPKs were analyzed at specific
      time points after release from arrest. Immune complex kinase assay and
      renaturation and phosphorylation assay in substrate-containing gel revealed that
      both 44- and 42-kDa MAPKs had activities in the G1 through S and G2/M phases and
      were activated biphasically, in the G1 phase and around the M phase. MAPKs were
      inactivated in metaphase-arrested cells. The amount of MAPKs did not change
      significantly in the cell cycle. In the G1, S, and G2/M phases, MAPKs were
      phosphorylated on both tyrosine and threonine residues and dephosphorylated in
      metaphase-arrested cells. Our data suggest that MAPKs may play some role in the
      cell cycle other than G0/G1 transition.

PMID- 1400348
TI  - Complete primary structure and tissue expression of chicken pectoralis M-protein.
AB  - M-Protein (165 kDa) is a structural constituent of myofibrillar M-band in
      striated muscle. We generated a monoclonal antibody which recognized a 165-kDa
      protein from chicken pectoralis muscle in immunoblot analysis and stained the M
      band under immunofluorescence microscopy. By screening a lambda gt11 cDNA library
      from chicken embryonic pectoralis muscle with this antibody, we isolated a cDNA
      clone encoding the M-protein. Northern blot analysis showed that M-protein mRNA
      is expressed in pectoralis and cardiac muscle but not in gizzard smooth muscle or
      non-muscle tissues. Moreover, the anterior latissimus dorsi muscle, which
      consists almost exclusively of slow fiber types, contains no detectable levels of
      the mRNA. The full-length cDNA sequence predicted a 1,450-amino acid polypeptide
      with a calculated molecular weight of 163 x 10(3). The encoded protein contains
      several copies of two different repetitive motifs: five copies of fibronectin
      type III repeats are in the middle part of the predicted molecule, and two and
      four copies of the immunoglobulin C2-type repeats are located toward the NH2
      terminal and COOH-terminal regions, respectively. This indicates that M-protein,
      along with other thick filament-associated proteins such as C-protein, twichin,
      and titin, belongs to the superfamily of cytoskeletal proteins with
      immunoglobulin/fibronectin repeats.

PMID- 1400349
TI  - Neurotrophic action of gliostatin on cortical neurons. Identity of gliostatin and
      platelet-derived endothelial cell growth factor.
AB  - Gliostatin is a polypeptide growth inhibitor of apparent M(r) = 100,000 with a
      homodimeric structure comprising two 50-kDa subunits, acting on astrocyte as well
      as astrocytoma cells (Asai, K., Hirano, T., Kaneko, S., Moriyama, A., Nakanishi,
      K., Isobe, I., Eksioglu, Y.Z., and Kato, T. (1992) J. Neurochem., 59, 307-317).
      The amino acid sequences of 13 tryptic peptides including the amino terminus were
      completely identical to those of platelet-derived endothelial cell growth factor
      (PD-ECGF) (Ishikawa, F., Miyazono, K., Hellman, U., Drexler, H., Wernstedt, C.,
      Hagiwara, K., Usuki, K., Takaku, F., Risau, W., and Heldin, C.-H. (1989) Nature
      338, 557-562). Gliostatin and PD-ECGF, purified from human placenta, shared
      growth inhibition on glial cells and growth promotion on endothelial cells, and
      exhibited similar values for half-maximal dose of glial growth inhibition (ID50 =
      1.3 nM) and the half-maximal concentration of endothelial growth promotion (EC50
      = 1.0 nM), suggesting that both factors evoke the biological actions through an
      identical receptor on each cell surface. We have further demonstrated evidence of
      a novel neurotrophic action of gliostatin/PD-ECGF toward embryonic rat cortical
      neurons in culture. The half-maximal concentration of gliostatin/PD-ECGF for
      neurotrophic action was 0.3 nM. All actions on glial, endothelial, and neuronal
      cells, were abolished by a monoclonal antibody against gliostatin. These data
      indicate that gliostatin/PD-ECGF may play important roles on development and
      regeneration of the central nervous system and may also involve the induction of
      angiogenesis for the formation of blood brain barrier.

PMID- 1400350
TI  - Casein kinase II phosphorylates p34cdc2 kinase in G1 phase of the HeLa cell
      division cycle.
AB  - The activity of p34cdc2 kinase is regulated in the phases of vertebrate cell
      cycle by mechanisms of phosphorylation and dephosphorylation. In this paper, we
      demonstrate that casein kinase II (CKII) phosphorylates p34cdc2 in vivo and in
      vitro at Ser39 during the G1 phase of HeLa cell division cycle. Human p34cdc2
      shows a typical phosphorylation sequence motif site for CKII at Ser39 (ES39EEE).
      In our experiments, either p34cdc2 expressed and purified from bacteria or
      p34cdc2 immunoprecipitated from HeLa cells enriched in G1 by elutriation were
      substrates for in vitro phosphorylation by CKII. Phosphoamino acid analysis, N
      chlorosuccinimide mapping, and two-dimensional tryptic mapping of p34cdc2
      phosphorylated in vitro were performed to determine the phosphorylation site. A
      synthetic peptide spanning residues 33-50 of human p34cdc2, including the CKII
      site, was used to map the site. In addition, phosphorylation at Ser39 also occurs
      in vivo, since p34cdc2 is phosphorylated during G1 on serine, and its two
      dimensional tryptic map shows two phosphopeptides that comigrate exactly with the
      synthetic peptides used as standard.

PMID- 1400351
TI  - Identification of the prostacyclin receptor by use of [15-3H1]19-(3-azidophenyl)
      20-norisocarbacyclin, an irreversible specific photoaffinity probe.
AB  - The prostaglandin I (PGI2) receptor of mouse mastocytoma P-815 cells was
      characterized by photo-affinity labeling with the stable PGI2 analogue [15-3H1]
      19-(3-azidophenyl)-20-norisocarbacyclin ([3H] APNIC) used as a potential
      photoaffinity probe for the receptor. [3H]APNIC bound to the mastocytoma membrane
      with high affinity and in a saturable manner. Scatchard plot analysis indicated a
      single binding site with a Kd of 4.7 nM and a Bmax of 0.58 pmol/mg protein. The
      binding of [3H]APNIC was dose dependently inhibited by APNIC and iloprost,
      another stable PGI2 agonist, and to a much lesser extent by PGE2. The binding of
      the radioligand showed sensitivity to the guanine nucleotide guanosine 5'-O-(3
      thio-triphosphate) (GTP gamma S). Photolysis of [3H]APNIC-prelabeled membranes
      resulted in incorporation of radiolabel into a protein of approximately 43 kDa.
      Photolabeling was inhibited by PGI2 agonists and other prostaglandins with
      specificity for the PGI2 receptor and was modulated by GTP gamma S. A protein of
      approximately 45 kDa was also labeled by [3H]APNIC in the membrane of porcine
      platelets, membranes that are known to be abundant in PGI2 receptors. These
      results demonstrate that [3H]APNIC specifically labels a protein that may
      represent the PGI2 receptor and that this radioprobe will be a useful reagent for
      further characterization and purification of the PGI2 receptor.

PMID- 1400352
TI  - Mutational analysis of the consensus nucleotide binding sequences in the rat
      liver mitochondrial ATP synthase beta-subunit.
AB  - The coupling step in the biosynthesis of ATP in biological systems is generally
      believed to involve an energy-requiring release of ATP bound to the beta-subunit
      of the ATP synthase complex. A molecular description of the ATP binding site on
      the beta-subunit is, therefore, critical to understanding the mechanism of
      coupling in the enzyme. Previously, we reported that a purified, bacterially
      expressed rat liver beta-subunit binds adenine nucleotides tightly and
      specifically (Garboczi, D. N., Hullihen, J. H., and Pedersen, P. L. (1988) J.
      Biol. Chem. 263, 15694-15698). In order to assess the contribution of various
      regions of the isolated beta-subunit to the ATP binding site we have
      systematically deleted four different regions: the N-terminal region, the Walker
      A consensus region, the Walker B consensus region (Walker, J. E., Saraste, M.,
      Runswick, M. J., and Gay, N. (1982) EMBO J. 1, 945-951), and a "C" region, which,
      like the A and B regions, bears homology to adenylate kinase. Plasmids directing
      the expression of double deletions of A and B regions, and B and C regions were
      also constructed. In addition, 2 residues outside of these regions, His-177 and
      Tyr-345, which have been predicted to play a central role in nucleotide binding,
      were mutated. Rabbit antisera to synthetic peptides of the A and C regions
      verified the identity of the bacterially expressed mutant proteins. Seven of the
      eight mutant proteins overexpressed in Escherichia coli were resistant to E. coli
      proteases in the preparative stages, as predicted for compact folded proteins.
      Furthermore, circular dichroism spectropolarimetry revealed no profound
      structural alterations in the purified mutant proteins. Relative to the
      overexpressed full-length beta-subunit, the mutant lacking the A consensus region
      suffered a 30-fold loss of affinity for ATP and a loss of specificity for 2'(3')
      O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP) over 2'(3')-O-(2,4,6
      trinitrophenyl)adenosine 5'-monophosphate. The mutant proteins lacking either the
      N-terminal region or the B region exhibited nucleotide binding properties similar
      to the full-length beta-subunit, whereas the mutant protein lacking the C region
      suffered an order of magnitude reduction in affinity for ATP. The affinity of the
      A and B region double deletion was indistinguishable from the A region deletion
      in regard to TNP-ATP binding, while the double deletion mutant lacking the B and
      C regions was not stably expressed in the E. coli SE6004.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1400354
TI  - Epidermal growth factor receptor in synaptic fractions of the rat central nervous
      system.
AB  - Functional relationships between epidermal growth factor (EGF) and neural tissues
      have of late attracted increasing interest. However, in spite of reported EGF
      effects on neurons, the expression of the EGF receptor (EGF-R) has not yet been
      unambiguously demonstrated in these cells. This 170-kDa protein bears an
      intracellular tyrosine kinase domain in which activity is ligand-dependent. We
      give definitive evidence here for its presence in neonatal and adult rat neurons
      showing also, for the first time, its binding and functional tyrosine kinase
      activities in the synaptic region. Immunohistochemistry using a polyclonal
      antibody prepared against the receptor purified from rat liver showed positive
      staining localized exclusively to neurons without regionalization to any
      particular brain zone. Binding studies made in Percoll-obtained synaptosomes
      revealed specific high affinity 125I-EGF binding sites (Kd, 1.42 x 10(-10) +/-
      0.58 M) accounting for 17% of total binding and a great majority of low affinity
      (Kd, 2.55 x 10(-9) +/- 0.35 M) binding sites. Higher binding capacity was found
      in synaptosomal fractions obtained from newborn rats. The identity of the
      synaptosomal EGF binding activity with the 170-kDA EGF-R protein was demonstrated
      by cross-linking experiments. Furthermore, EGF-Affi-Prep affinity chromatography
      adsorbs a 170-kDa protein with EGF-R immunoreactivity from whole homogenates of
      adult rat brain. Phosphorylation assays made in freeze-thawed or intact
      synaptosomes showed EGF-induced tyrosine phosphorylation in the range of 170-,
      126-150-, 124-, 113-, 98-, and 70-kDa proteins including the EGF-R. Thus, the EGF
      R/EGF regulatory system could have a role in synaptic function that remains to be
      explored.

PMID- 1400353
TI  - Nucleotide exchange, structure, and mechanical properties of filaments assembled
      from ATP-actin and ADP-actin.
AB  - Actin monomers with bound ATP, ADP, or fluorescent analogues of these nucleotides
      exchange the nucleotide on a second time scale, whereas filaments assembled from
      each of these species exchange their nucleotide with the solution at least 1,000
      times slower than monomers. Filaments assembled from either ATP-actin or ADP
      actin are indistinguishable by electron microscopy after negative staining. The
      dynamic elasticity and viscosity of filaments assembled from ATP-actin or ADP
      actin or mixtures of these two species are the same over a wide range of
      frequencies. These observations do not support a recent suggestion (Janmey, P.
      A., Hvidt, S., Oster, G. F., Lamb, J., Stossel, T. P., and Hartwig, J. H. (1990)
      Nature 347, 95-99) that ATP hydrolysis within actin filaments stiffens the
      polymer and alters both their structure and affinity for nucleotides. The
      difference in observations between these two studies may be related to time
      dependent changes in ADP-actin prepared in slightly different ways.

PMID- 1400355
TI  - Crystal structure of recombinant human interleukin-4.
AB  - The crystal structure of recombinant human interleukin-4 (rhuIL-4) was initially
      determined at 3.5-A resolution by multiple isomorphous replacement techniques and
      subsequently refined to a resolution of 2.35 A by simulated annealing. The final
      crystallographic R-factor, based on all data in the range 6.0-2.35 A (7470
      reflections), is 0.232. Bond lengths and bond angles in the molecule have root
      mean square deviations from ideal values of 0.016 A and 2.4 degrees,
      respectively. The overall structure is highly compact and globular with a
      predominantly hydrophobic core. The main structural feature of rhuIL-4 is a four
      alpha-helix bundle, which composes approximately 58% of the structure. The
      helices are arranged in a left-handed antiparallel bundle with two overhand
      connections. Within these connections is a two-stranded antiparallel beta-sheet.
      Both the tertiary and secondary structures of rhuIL-4 are similar to those of
      human granulocyte-macrophage colony-stimulating factor. Critical regions for
      receptor binding are proposed.

PMID- 1400356
TI  - Autocrine and paracrine effects of endothelium-derived relaxing factor on
      intracellular Ca2+ of endothelial cells and vascular smooth muscle cells.
      Identification by two-dimensional image analysis in coculture.
AB  - To elucidate the effects of endothelium-derived relaxing factor (EDRF) released
      from vascular endothelial cells (ECs) on handling of intracellular calcium ion
      (Ca2+i) in ECs themselves and vascular smooth muscle cells (VSMCs), we measured
      the Ca2+i by two-dimensional digital image analysis of fura-2-loaded ECs and
      VSMCs in tissue culture. In isoculture of one cell type, adenosine triphosphate
      (ATP, 1 microM) transiently increased the Ca2+i of both ECs and VSMCs. High-K+
      depolarization or angiotensin II also elevated the Ca2+i of VSMCs, whereas
      neither stimulants changed the Ca2+i of ECs. In coculture of ECs with VSMCs, the
      same dose of ATP rapidly increased the Ca2+i of ECs and then transiently
      decreased the Ca2+i of VSMCs to below the resting level. The maximal Ca2+i
      modulating effects of ATP on both cell types were reproducible after the second
      application of ATP. Three kinds of EDRF blockers (L-NG-monomethylarginine,
      methemoglobin, or methylene blue) potentiated the ATP-induced Ca2+i rise in ECs
      and attenuated the Ca2+i reduction in VSMCs, suggesting the autocrine and
      paracrine effects of EDRF on ECs and VSMCs, respectively. However, neither
      indomethacin, superoxide dismutase, nor neutralizing monoclonal antibody to
      endothelin-1 altered the second responses. Thus, two-dimensional Ca2+i image
      analysis of ECs and VSMCs in coculture enabled direct visualization of the EDRF
      actions in ECs and VSMCs and their modifications.

PMID- 1400357
TI  - Gene expression of mouse choline acetyltransferase. Alternative splicing and
      identification of a highly active promoter region.
AB  - Seven types of mRNA for choline acetyltransferase that differ in the 5'-noncoding
      region were identified in the mouse spinal cord by cDNA cloning and polymerase
      chain reaction. Among these transcripts, the M-type mRNA corresponding to the
      previously cloned mouse cDNA was most abundant in the spinal cord of mouse. A
      mouse genomic DNA clone containing the 5'-region of choline acetyltransferase
      mRNA was isolated and sequenced. Comparison of the sequences between the cDNAs
      and the genomic DNA revealed that the different mRNA species were transcribed
      from different promoter regions and produced by differential splicing. Two murine
      cholinergic cell lines, NS20Y and NG108-15, were shown to express the M-type mRNA
      almost exclusively, and were therefore used to study transcription of M-type
      mRNA. Fragments of the 5'-region of choline acetyltransferase gene were ligated
      with chloramphenicol acetyltransferase reporter gene and introduced into cultured
      cells. The fragment from -2752 to +46, which contained the M-type exon, a TATA
      box like element upstream of the M-type exon, and the downstream intron, induced
      a significant expression of CAT activity in neuronal but not in non-neuronal cell
      lines. This result indicates that this region of choline acetyltransferase gene
      contains elements that regulate neuron-specific expression of choline
      acetyltransferase activity. However, there was no parallel correlation between
      reporter gene expression in the transfected cells and intrinsic choline
      acetyltransferase activity in these neuronal cell lines. Possible mechanisms that
      would explain this observation are discussed.

PMID- 1400359
TI  - A novel intestinal trans-factor (NF-LPH1) interacts with the lactase-phlorizin
      hydrolase promoter and co-varies with the enzymatic activity.
AB  - The promoter of the pig lactase-phlorizin hydrolase was cloned and showed to be
      functional in the human intestinal cell line Caco2. The proximal promoter was
      analyzed for binding of nuclear proteins from small intestine and liver. DNase I
      footprinting and electrophoretic mobility shift assays show, that an intestinal
      nuclear factor (NF-LPH1) binds to a sequence (-40 to -54) located close to the
      TATA-box. Enterocytes from newborn pigs with high lactase activity contain high
      amounts of NF-LPH1, whereas enterocytes from adult pigs with low lactase activity
      contain low amounts of NF-LPH1. The liver does not contain lactase activity, and
      NF-LPH1 is not present in liver nuclear extracts in detectable amounts. This
      indicates that NF-LPH1 is involved in the decline of lactase at weaning and may
      be of importance for the molecular explanation of hypolactasia in humans. It was
      demonstrated by transfection of two different promoter-reporter gene constructs
      into Caco2 cells, that there are additional cis-element(s) in the region -142 to
      approximately -980, which are important for the transcription of the lactase
      phlorizin hydrolase gene.

PMID- 1400358
TI  - Complete structure of the murine C4b-binding protein gene and regulation of its
      expression by dexamethasone.
AB  - C4b-binding protein (C4BP) is involved in the fluid-phase regulation of the
      classical pathway of complement. A murine genomic library was screened, and five
      clones were selected that covered the remaining four exons in the 5'-region of
      the C4BP gene. Together with previous work (Barnum, S. R., Kristensen, T.,
      Chaplin, D. D., Seldin, M. F., and Tack, B. F. (1989) Biochemistry 28, 8312
      8317), the entire C4BP gene has now been shown to be 23 kilobases (kb) long and
      comprised of 10 exons ranging in size from 86 to 442 base pairs (bp). Primer
      extension analysis revealed the major transcription start site to be 46 bp
      upstream of the published cDNA start site. Northern blot analysis of RNA isolated
      from several mouse tissues demonstrated that the C4BP gene is expressed in a
      liver-specific manner. Several regions homologous to known response elements were
      identified upstream of the C4BP gene including a strong hepatocyte nuclear factor
      1 binding site and four putative glucocorticoid response elements. Furthermore,
      dexamethasone increased C4BP mRNA and protein levels in the mouse liver cell
      line, NMuLi. The stimulation of C4BP gene expression was rapid and independent of
      protein synthesis. These results suggest dexamethasone induction of the C4BP gene
      is a primary response and therefore a transcriptional effect. Inhibition of the
      dexamethasone effect on C4BP by actinomycin D supports this theory. These studies
      also provide evidence that, for optimal induction of the C4BP gene, the
      glucocorticoid receptor complex may cooperatively interact with accessory
      transcription factors. It is likely that stimulation of C4BP gene expression by
      dexamethasone may allude to a mechanism by which glucocorticoids exert their anti
      inflammatory effects.

PMID- 1400360
TI  - Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary
      methemoglobinemia type I (red cell type).
AB  - Nucleotide substitutions in the gene for NADH-cytochrome b5 reductase were
      identified in three independent probands of hereditary methemoglobinemia type I.
      Patients in Kagoshima and Okinawa in Japan were shown to possess the same base
      change, from guanine to adenine at codon 57, which results in amino acid
      substitution from Arg to Gln. This nucleotide change was the same as formerly
      found in a patient in Toyoake, Japan (Katsube, T., Sakamoto, N., Kobayashi, Y.,
      Seki, R., Hirano, M., Tanishima, K., Tomoda, A., Takazakura, E., Yubisui, T.,
      Takeshita, M., Sakaki, Y., and Fukumaki, Y. (1991) Am. J. Hum. Genet. 48, 799
      808). A type I patient in Italy was shown to have a base change from guanine to
      adenine at codon 105 which causes substitution from Val to Met. To characterize
      the enzymes of type I patients, Arg-57----Gln and Val-105----Met mutant enzymes
      were overexpressed in Escherichia coli and purified to homogeneity. kcat/Km
      values (NADH) of these two enzymes were 25% in Arg-57----Gln and 14.5% in Val-105
      ---Met compared with that of the wild type enzyme, while the value of type II
      (generalized, severe form of the disease) mutant enzyme was 3% of the normal
      value (Yubisui, T., Shirabe, K., Takeshita, M., Kobayashi, Y., Fukumaki, Y.,
      Sakaki, Y., and Takano, T. (1991) J. Biol. Chem. 266, 66-70). The type I mutant
      enzymes were less heat-stable and more susceptible to proteinase treatment than
      the wild type. From these results we conclude that restriction of enzyme
      deficiency to red cells in hereditary methemoglobinemia type I may be generally
      derived from instability and increased proteolytic susceptibility of variant NADH
      cytochrome b5 reductases due to a point mutation.

PMID- 1400361
TI  - The heat-shock protein ClpB in Escherichia coli is a protein-activated ATPase.
AB  - The clpB gene in Escherichia coli encodes a heat-shock protein that is a close
      homolog of the clpA gene product. The latter is the ATPase subunit of the
      multimeric ATP-dependent protease Ti (Clp) in E. coli, which also contains the 21
      kDa proteolytic subunit (ClpP). The clpB gene product has been purified to near
      homogeneity by DEAE-Sepharose and heparin-agarose column chromatographies. The
      purified ClpB consists of a major 93-kDa protein and a minor 79-kDa polypeptide
      as analyzed by polyacrylamide gel electrophoresis in the presence of sodium
      dodecyl sulfate. Upon gel filtration on a Superose-6 column, it behaves as a 350
      kDa protein. Thus, ClpB appears to be a tetrameric complex of the 93-kDa subunit.
      The purified ClpB has ATPase activity which is stimulated 5-10-fold by casein. It
      is also activated by insulin, but not by other proteins, including globin and
      denatured bovine serum albumin. ClpB cleaves adenosine 5'-(alpha,beta-methylene)
      triphosphate as rapidly as ATP, but not adenosine 5'-(beta,gamma-methylene)
      triphosphate. GTP, CTP, and UTP are hydrolyzed 15-25% as well as ATP. ADP
      strongly inhibits ATP hydrolysis with a Ki of 34 microM. ClpB has a Km for ATP of
      1.1 mM, and casein increases its Vmax for ATP without affecting its Km. A Mg2+
      concentration of 3 mM is necessary for half-maximal ATP hydrolysis. Mn2+ supports
      ATPase activity as well as Mg2+, and Ca2+ has about 20% their activity. Anti-ClpB
      antiserum does not cross-react with ClpA nor does anti-ClpA antiserum react with
      ClpB. In addition, ClpB cannot replace ClpA in supporting the casein-degrading
      activity of ClpP. Thus, ClpB is distinct from ClpA in its structural and
      biochemical properties despite the similarities in their sequences.

PMID- 1400362
TI  - Cell surface heparan sulfate proteoglycans from human vascular endothelial cells.
      Core protein characterization and antithrombin III binding properties.
AB  - Human aortic endothelial cells (HAEC) and human umbilical vein endothelial cells
      (HUVEC) were labeled with 35SO(4)2- for 48 h. The membrane-associated
      proteoglycans were solubilized from these monolayers with detergent and purified
      by ion-exchange chromatography on Mono Q, incorporation in liposomes, and gel
      filtration. The liposome-intercalated proteoglycans were 125I-iodinated and
      treated with heparitinase before SDS-polyacrylamide gel electrophoresis. Radio
      labeled proteins with apparent molecular masses of 130, 60, 46, 35, and 30 kDa
      (HAEC) and 180, 130, 62, 43, and 35 kDa (HUVEC) were detected by autoradiography.
      Further characterization by affinity chromatography on immobilized monoclonal
      antibodies and by Northern blot analysis provided evidence for the expression of
      syndecan, glypican, and fibroglycan in human endothelial cells. Most of the
      heparan sulfate which accumulated in the subendothelial matrix was implanted on a
      400-kDa core protein. This protein was immunologically related to perlecan and
      bound to fibronectin. Binding studies on immobilized antithrombin III suggested
      that all membrane-associated heparan sulfate proteoglycan forms had the capacity
      to bind to antithrombin III but that high affinity binding was more typical for
      glypican. Most of the proteoglycans isolated from the extracellular matrix also
      bound only with low affinity to antithrombin III. These results imply that
      glypican may specifically contribute to the antithrombotic properties of the
      vascular wall.

PMID- 1400363
TI  - Regulation of translation initiation factor gene expression during human T cell
      activation.
AB  - Activation of quiescent T cells leads to a dramatic increase in the rate of
      protein synthesis. It is believed that this pronounced increase of protein
      synthesis is regulated primarily at the level of translational initiation.
      Although considerable evidence demonstrates that translational initiation can be
      regulated at the post-translational level by the
      phosphorylation/dephosphorylation of translation initiation factors (eIFs) such
      as eIF-4E and eIF-2 alpha, additional mechanisms of eIF gene expression may also
      play a role in the regulation of translation in quiescent cells and/or during
      their subsequent induction to enter the cell cycle. To address this issue, gene
      expression of eIF-2 alpha, -4E, and -4A was studied in quiescent human peripheral
      blood T cells following stimulation through the T cell receptor-CD3 complex.
      Quiescent T cells expressed low levels of eIF-2 alpha, -4E, and -4A mRNAs and
      proteins as compared to proliferating T cells. Activation of resting T cells
      resulted in a rapid increase (20-50-fold) in the levels of these three mRNAs.
      This increase did not require new protein synthesis. Furthermore, transcription
      rates of these three eIF genes showed only minor increase over the induction
      period as measured by nuclear run-on assays. Despite the rapid increase in
      initiation factor mRNA levels, increases in eIF protein levels lagged
      significantly behind. Western blot analysis also showed that the protein levels
      of the three eIFs were differentially increased. eIF-4A protein levels increased
      in proportion to the observed increase in cellular protein synthetic activity
      while the increases in eIF-4E and eIF-2 alpha proteins were proportionately less.
      The low levels of eIF proteins in quiescent T cells appear to correlate with low
      protein synthesis rate in such cells. The induction of eIF proteins by post
      transcriptional/translational mechanisms appears to contribute to the pronounced
      stimulation of protein synthesis that occurs during T cell activation.

PMID- 1400364
TI  - Kinesin and cytoplasmic dynein binding to brain microsomes.
AB  - Movement of cellular organelles in a directional manner along polar microtubules
      is driven by the motor proteins, kinesin and cytoplasmic dynein. The binding of
      these proteins to a microsomal fraction from embryonic chicken brain is
      investigated here. Both motors exhibit saturation binding to the vesicles, and
      proteolysis of vesicle membrane proteins abolishes binding. The maximal binding
      for kinesin is 12 +/- 1.7 and 43 +/- 2 pmol per mg of vesicle protein with or
      without 1 mM ATP, respectively. The maximal binding for cytoplasmic dynein is 55
      +/- 3.8 and 73 +/- 3.7 pmol per mg of vesicle protein with or without ATP,
      respectively. These values correspond to 1-6 sites per vesicle of 100-nm
      diameter. The nonhydrolyzable ATP analog, adenyl-5'-yl imidodiphosphate (AMP
      PNP), inhibited kinesin binding to vesicles but increased kinesin binding to
      microtubules. An antibody to the kinesin light chain also inhibited vesicle
      binding to kinesin. In the absence but not presence of ATP, competition between
      the two motors for binding was observed. We suggest that there are two
      distinguishable binding sites for kinesin and cytoplasmic dynein on these
      organelles in the presence of ATP and a shared site in the absence of ATP.

PMID- 1400365
TI  - Calcium ionophore A23187 induces expression of the growth arrest and DNA damage
      inducible CCAAT/enhancer-binding protein (C/EBP)-related gene, gadd153. Ca2+
      increases transcriptional activity and mRNA stability.
AB  - gadd153 is a CCAAT/enhancer-binding protein (C/EBP)-related gene whose expression
      is induced in response to growth arrest and DNA damage. This investigation
      explored the possibility that Ca2+ might play a role in regulating expression of
      gadd 153. We have demonstrated that treatment of HeLa cells with the calcium
      ionophores A23187 and ionomycin leads to the induction of gadd153 mRNA. The
      induction was rapid; increases in mRNA were detected by 90 min of treatment, and
      near maximum levels were achieved within 5-h exposure to A23187. Elevated mRNA
      levels resulted from both an increase in the rate of gadd153 transcription and an
      increase in the stability of the gadd153 mRNA. The response was not dependent on
      protein kinase C nor was it coupled to c-fos expression. Buffering intracellular
      and extracellular Ca2+ by combined treatment with BAPTA-AM (acetoxymethyl ester
      form of bis(aminophenoxy)ethane N,N'-tetraacetic acid) and EGTA prevented the
      induction of gadd153 mRNA by A23187. In addition, these treatments prevented the
      induction of gadd153 mRNA in response to the DNA damaging agent methyl
      methanesulfonate. We conclude that intracellular Ca2+ plays a role in regulating
      gadd153 expression. More specifically, Ca2+ likely plays a role in the induction
      of gadd153 mRNA following DNA damage.

PMID- 1400366
TI  - Sequence similarities between the RP4 Tra2 and the Ti VirB region strongly
      support the conjugation model for T-DNA transfer.
AB  - Transfer genes of the IncP plasmid RP4 are grouped in two separate regions,
      designated Tra1 and Tra2. Tra2 gene products are proposed to be mainly
      responsible for the formation of mating pairs in conjugating cells. To provide
      information relevant to understanding the function of Tra2 gene products, the
      nucleotide sequence of the entire RP4 Tra2 region is presented here. Twelve open
      reading frames were identified in the Tra2 core region, being essential for
      intraspecific Escherichia coli matings. Predicted sizes of 11 of the 12 Tra2
      polypeptides could be verified by expression in E. coli. Based on hydropathy plot
      analysis, most of the Tra2 open reading frames encode proteins that may interact
      with membranes. Interestingly, six of the predicted Tra2 gene products exhibited
      significant sequence similarities to gene products encoded by the VirB operon of
      the Agrobacterium Ti plasmid. VirB proteins are thought to function in the
      formation of a transmembrane structure that mediates the passage of T-DNA
      molecules from bacteria into plant cells. Because of this analogy and the
      hydropathy of Tra2 gene products, we assume that the DNA transfer machineries
      acting in bacterial conjugation and T-DNA transfer are structurally and
      functionally similar. Therefore, the data presented here, support the hypothesis
      that Ti vir and IncP tra genes evolved from a common ancestor. This suggestion is
      favored by previous findings of sequence similarities between the IncP and Ti DNA
      transfer system.

PMID- 1400367
TI  - Influence of a strong-binding myosin analogue on calcium-sensitive mechanical
      properties of skinned skeletal muscle fibers.
AB  - The ability of strong-binding myosin heads to activate the thin filament was
      investigated by incubating skinned single muscle fibers with N-ethylmaleimide
      (NEM) modified myosin subfragment-1 (S1). Isometric force was influenced in a
      complex manner: during maximal calcium activation, NEM-S1 inhibited force with
      half-maximal inhibition at 20 microM while at submaximal calcium, NEM-S1
      potentiated force with greatest effect at 6 microM. When fibers were treated with
      NEM-S1 (4-8 microM), the tension-pCa (-log [Ca2+]) relationship became less steep
      (i.e. the Hill coefficient decreased from 5.4 to 3.0 upon treatment with NEM-S1),
      but the midpoint was unchanged. These results support the idea that strong
      binding of intrinsic heads contributes to the cooperativity observed in Ca2+
      activation of force. The NEM-S1-induced increase in force at low Ca2+ was
      associated with an acceleration of a kinetic transition, and this transition was
      activated to near maximum while force was not. The rate of force redevelopment
      following restretch (ktr) at submaximal calcium was increased by NEM-S1 in a
      concentration-dependent manner, yielding a maximum rate at low [Ca2+] which was
      similar to that observed during full activation. The effects of NEM-S1 on force
      and ktr indicate that strong-binding myosin cross-bridges are involved in
      activation of the thin filament.

PMID- 1400368
TI  - Isolation and characterization of a novel acidic polysaccharide containing
      tartrate and glyoxylate residues from the mineralized scales of a unicellular
      coccolithophorid alga Pleurochrysis carterae.
AB  - The characterization of mineral-associated polyanions from the unicellular alga
      Pleurochrysis carterae is described. This species is useful for the study of
      mineralization, because it produces calcified scales known as coccoliths in
      homogeneous cell culture. Three acidic polysaccharides (PS-1, PS-2, and PS-3)
      were extracted from the coccoliths with EDTA and were separated and purified by
      differential precipitation with magnesium ions and chromatography on DEAE
      cellulose. PS-1 and PS-3 are predominantly polymers of galacturonic acid
      containing lesser amounts of other monosaccharides. PS-2 has an unusual
      structure. Chemical, enzymatic, and two-dimensional NMR analyses demonstrate that
      the repeating unit of PS-2 is [----4)D-glucuronate(beta 1----2)meso-tartrate(3---
      1)glyoxylate(1-]n. Thus PS-2 has a high density of negatively charged groups
      available for calcium ion binding, similar to the phosphoprotein polyanions of
      other species. Polysaccharides containing tartrate and/or glyoxylate have not
      been previously described; these residues may be introduced into PS-2 by a
      postpolymerization process involving oxidative cleavage of glucuronate or
      mannuronate residues.

PMID- 1400369
TI  - The interleukin-4-related lymphokines and their binding to hematopoietin
      receptors.

PMID- 1400370
TI  - The binding of human factor IX to endothelial cells is mediated by residues 3-11.
AB  - We have used chimeras and point mutations of recombinant coagulation factor IX to
      examine factor IX's specific interaction with bovine endothelial cells.
      Previously (Toomey, J. R., Smith, K. J., Roberts, H. R., and Stafford, D. W.
      (1992) Biochemistry 31, 1806-1808), we restricted the region of factor IX
      responsible for binding to endothelial cells to its Gla domain. Molecular
      modeling of the Gla domain of factor IX using the coordinates of the Gla domain
      of bovine prothrombin-(1-145) (Soriano-Garcia, M., Padmanabhan, K., deVos, A. M.,
      and Tulinsky, A. (1992) Biochemistry 31, 2554-2566) reveals two major surface
      determinants whose sequences differ among factors IX, X, and VII. A chimeric
      protein comprised of the Gla domain of factor VII with the remainder of the
      molecule of factor IX did not bind to the endothelial cell binding site. We
      changed residues 33, 34, 35, 39, and 40 to those of factor IX without restoring
      endothelial cell binding. Replacement of amino acid residues 3-10 with those of
      factor IX restored normal binding. With the knowledge that specific binding was
      localized to the first 11 amino acids, point mutations were made at residues
      predicted to be on the surface in this region of the factor IX molecule. Changing
      lysine 5 to alanine (K5A) or valine 10 to lysine (V10K) resulted in loss of
      binding with total retention of in vitro clotting activity. The lysine 5 to
      arginine (K5R) mutation also was fully active in vitro but displayed 3-fold
      tighter binding. In addition to defining the sequence of factor IX necessary for
      binding to endothelial cells, these results suggest that the binding site is not
      phospholipid but instead is specific, and in all likelihood, protein.

PMID- 1400371
TI  - Carbohydrate-binding proteins in bovine kidney have consensus amino acid
      sequences of annexin family proteins.
AB  - Ca(2+)-dependent carbohydrate-binding proteins were purified from bovine kidney
      extracts. Upon SDS-polyacrylamide gel electrophoresis under nonreducing
      conditions, the purified fraction gave doublet protein bands corresponding to 33
      kDa (p33) and 41 kDa (p41). Under reducing conditions, a single protein band
      (p33) was observed. p33 and p41 were submitted to proteolytic digestion with
      endoproteinase Lys-C, the peptides produced were separated by reversed-phase high
      performance liquid chromatography, and their amino acid sequences were determined
      by an automated gas-phase protein sequenator. Most of the resulting partial amino
      acid sequences of these proteins were strikingly homologous to annexin IV, an
      annexin family protein, i.e. Ca2+/phospholipid-binding proteins, especially in
      the consensus sequences. In the presence of Ca2+, both proteins bound to vesicles
      composed of phosphatidylserine and phosphatidylethanolamine, but not
      phosphatidylcholine. These results indicated that p33 and p41 are members of
      annexin family proteins.

PMID- 1400372
TI  - A novel subtype of endothelin receptors.
AB  - A new subtype of endothelin receptors with binding properties typical of "super
      high" affinity sites, i.e. with affinities in the picomolar range, were
      identified and characterized in several rat brain regions and atrium. The
      pharmacological profile of these sites is indicative of the endothelin receptor
      type B (ETB-R). These sites differ from the "conventional" high affinity sites
      (nanomolar range) in several respects; they do not induce phosphoinositide
      hydrolysis (whereas the high affinity sites do), and they are affected
      differently by deglycosylation. Thus, there appear to be at least two subtypes of
      the ETB-R, namely ETB1-R (super-high affinity sites) and ETB2-R (high affinity
      sites). We suggest the possibility that the super-high affinity sites are related
      to the vasodilatation property of endothelins, whereas the high affinity sites
      participate in their vasoconstrictive action.

PMID- 1400373
TI  - A novel laminin B1 chain variant in avian eye.
AB  - Two distinct recombinant cDNA clones having homology to mouse laminin B1 have
      been isolated from an adult chicken eye library by cross-species nucleic acid
      hybridization. DNA sequence analysis identified one cDNA as the chicken homologue
      of the prototypic EHS laminin B1 chain. The second recombinant cDNA encodes a
      portion of a laminin B1-like protein, which is neither the chicken homologue of
      laminin B1 nor s-laminin, and thus represents a new laminin B1 variant.

PMID- 1400374
TI  - A single change of histidine to glutamine alters the substrate preference of a
      stilbene synthase.
AB  - Stilbene and chalcone synthases are related polyketide synthases which use the
      same substrates but form different products. The environment of the condensing
      active site cysteine is highly conserved, except for the positions -2 and -3. All
      chalcone synthases contain Gln-Gln and prefer 4-coumaroyl-CoA as starter CoA
      ester, while the two known stilbene synthases contain Gln-His or His-Gln
      (preference phenylpropionyl-CoA and 4-coumaroyl-CoA, respectively). We
      investigated whether the presence and/or position of the histidine influences the
      substrate preference and the product specificity (stilbene or chalcone). The two
      amino acid motifs in the chalcone synthase from Pinus sylvestris (Gln-Gln) and in
      the stilbene synthases from P. sylvestris (Gln-His) and Arachis hypogaea (His
      Gln) were changed by site-directed mutagenesis into all sequence combinations as
      found in the natural enzymes. Assays with the mutant proteins showed that the
      histidine does not determine the product specificity. With the chalcone and the
      stilbene synthase from P. sylvestris, any sequence deviation reduced the activity
      without marked effects on the substrate preference. The stilbene synthase from A.
      hypogaea was different. The change from His-Gln to Gln-His abolished enzyme
      activity almost completely with all three substrates. The change to Gln-Gln
      selectively reduced the activity with 4-coumaroyl-CoA, and the kinetic analysis
      indicated a slight increase in Km and a 3-fold reduction of Vmax, when compared
      with the parent enzyme. This converted the enzyme from a resveratrol-forming into
      a dihydropinosylvin-forming stilbene synthase.

PMID- 1400375
TI  - Specificity of Zea mays histone deacetylase is regulated by phosphorylation.
AB  - Mono Q ion exchange high performance liquid chromatography (HPLC) reveals that
      the main histone deacetylase activity (HD1) of germinating Zea mays embryos
      consists of multiple enzyme forms. Chromatography of HD1 after treatment with
      alkaline phosphatase yields two distinct histone deacetylase forms (HD1-A, HD1
      B). The same is true for chromatography after phosphatase treatment of a total
      cell extract. One of these enzyme forms (HD1-A) is subject to phosphorylation,
      which causes a change in the substrate specificity of the enzyme, as shown with
      HPLC-purified individual core histone species; the substrate specificity for H2A
      increases more than 2-fold after phosphorylation, whereas the specificity for H3
      decreases to about 60%. The total histone deacetylase activity is quantitatively
      released from isolated nuclei after extraction with moderate ionic strength
      buffers; no significant residual enzyme activity could be detected in the nuclear
      matrix.

PMID- 1400376
TI  - Antagonistic effect of interferon-gamma on tat-induced transactivation of HIV
      long terminal repeat.
AB  - Interferon-gamma (IFN-gamma) has been shown to inhibit human immunodeficiency
      virus (HIV) replication in macrophages. However, the site of its effect on the
      HIV infectious cycle is unknown. We show here that IFN-gamma inhibits the
      transactivation of HIV long terminal repeat (LTR) during viral infection and that
      it antagonizes tat effect in HT4LacZ-1 cells. HT4LacZ-1 is an indicator CD4+ HeLa
      cell line for HIV infectivity, because it harbors a HIV LTR-LacZ gene susceptible
      to transactivation by tat. It was used in combination with a computer-assisted
      image analyzer to quantify: (i) the number of transactivated foci following HIV
      infection, (ii) their individual level of transactivation, and (iii) the fusion
      potency of infected cells. IFN-gamma induced a 75% decrease of the number of
      transactivated foci following infection of HT4LacZ-1 cells by HIV. The remaining
      25% foci still susceptible to transactivation were transactivated at a lower
      level than in control cultures, and the fusion potency of infected cells was
      strongly decreased. IFN-gamma acted after HIV entry into the cell and
      independently of reverse transcription. IFN-gamma antagonized tat-induced LTR
      transactivation: it inhibited transactivation of HT4LacZ-1 cells when tat was
      provided either from a SV40-based expression vector of tat or by polyethylene
      glycol-induced cell fusion with HeLa-tat-III cells. These results suggest that
      IFN-gamma affects the expression or the activity of cellular factors interacting
      with tat and that the high level of IFN-gamma production associated with HIV
      infection plays a role in the establishment of HIV latency.

PMID- 1400377
TI  - Effects of mutations of conserved Lys-155 and Thr-156 residues in the phosphate
      binding glycine-rich sequence of the F1-ATPase beta subunit of Escherichia coli.
AB  - beta Lys-155 in the glycine-rich sequence of the beta subunit of Escherichia coli
      F1-ATPase has been shown to be near the gamma-phosphate moiety of ATP by affinity
      labeling (Ida, K., Noumi, T., Maeda, M., Fukui, T., and Futai, M. (1991) J. Biol.
      Chem. 266, 5424-5429). For examination of the roles of beta Lys-155 and beta Thr
      156, mutants (beta Lys-155-->Ala, Ser, or Thr; beta Thr-156-->Ala, Cys, Asp, or
      Ser; beta Lys-155/beta Thr-156-->beta Thr-155/beta Lys-156; and beta Thr-156/beta
      Val-157-->beta Ala-156/beta Thr-157) were constructed, and their properties were
      studied extensively. The beta Ser-156 mutant was active in ATP synthesis and had
      approximately 1.5-fold higher membrane ATPase activity than the wild type. Other
      mutants were defective in ATP synthesis, had < 0.1% of the membrane ATPase
      activity of the wild type, and showed no ATP-dependent formation of an
      electrochemical proton gradient. The mutants had essentially the same amounts of
      F1 in their membranes as the wild type. Purified mutant enzymes (beta Ala-155,
      beta Ser-155, beta Ala-156, and beta Cys-156) showed low rates of multisite (<
      0.02% of the wild type) and unisite (< 1.5% of the wild type) catalyses. The k1
      values of the mutant enzymes for unisite catalysis were lower than that of the
      wild type: not detectable with the beta Ala-156 and beta Cys-156 enzymes and
      10(2)-fold lower with the beta Ala-155 and beta Ser-155 enzymes. The beta Thr-156
      ->Ala or Cys enzyme showed an altered response to Mg2+, suggesting that beta Thr
      156 may be closely related to Mg2+ binding. These results suggest that beta Lys
      155 and beta Thr-156 are essential for catalysis and are possibly located in the
      catalytic site, although beta Thr-156 could be replaced by a serine residue.

PMID- 1400378
TI  - Casein kinase II and the tumor suppressor protein P53 associate in a molecular
      complex that is negatively regulated upon P53 phosphorylation.
AB  - Selective immunoisolation of P53 from Sf9 cells coexpressing wild-type P53 and
      casein kinase II yielded a preparation containing casein kinase II, thus
      suggesting that the two proteins may associate in a molecular complex in the
      intact cell. Such a complex could indeed be demonstrated in vitro between
      purified recombinant P53 and oligomeric casein kinase II and was shown to
      dissociate when P53 became phosphorylated by the kinase. This suggested that the
      P53 C-terminal domain, which contains the casein kinase II phosphorylation site
      was involved in the protein-protein interaction; this was confirmed by the fact
      that an anti-P53 monoclonal antibody directed to that domain inhibited the P53
      casein kinase II association. Studies with isolated recombinant casein kinase II
      subunits disclosed that although the alpha (catalytic) subunit could
      phosphorylate P53, the formation of a stable P53-casein kinase II association
      required the presence of the beta subunit of the kinase. This was confirmed by
      immunoisolation of a P53-beta subunit complex from cells expressing both
      polypeptides. Although the biological significance of a reversible P53-casein
      kinase II molecular complex in the control of cell proliferation processes
      remains to be defined, these observations suggest the possibility of a novel
      mechanism regulating P53 and casein kinase II activities in the intact cell.

PMID- 1400379
TI  - Identification of a cis-acting element that enhances the pigment cell-specific
      expression of the human tyrosinase gene.
AB  - To identify the cis-acting element that is responsible for the pigment cell
      specific expression of the human tyrosinase gene, we analyzed the promoter
      activity of its 5'-flanking region by transient expression assays. The fusion
      genes were constructed by inserting the 5'-flanking region of the human
      tyrosinase gene upstream from the firefly luciferase gene and were introduced
      into human melanoma cells and HeLa cells. We thus found the element, located
      between 2.7 and 1.8 kilobase pairs upstream from the transcription initiation
      site, that enhances the transient expression of the luciferase reporter gene in
      melanoma cells, but not in HeLa cells, the tyrosinase gene expression of which is
      not detectable. Using the fusion genes containing putative enhancer elements
      under the control of the heterologous simian virus 40 promoter, we identified the
      pigment cell-specific enhancer of approximately 200 base pairs (bp) between -2.0
      and -1.8 kilobase pairs and localized the core sequence to a 39-bp region. This
      39-bp core element was then confirmed to direct the melanoma cell-specific
      expression of the reporter gene under the tyrosinase gene promoter. We thus
      propose that this core element is responsible for the pigment cell-specific
      expression of the human tyrosinase gene.

PMID- 1400380
TI  - CDC43 and RAM2 encode the polypeptide subunits of a yeast type I protein
      geranylgeranyltransferase.
AB  - The question regarding the identity of the alpha and beta subunits of the yeast
      type I protein geranylgeranyltransferase was explored using prokaryotic
      expression of candidate genes. The Saccharomyces cerevisiae CDC43 and RAM2 genes
      were expressed in Escherichia coli and cell extracts examined for the ability to
      transfer [3H]geranylgeranyl diphosphate to an appropriate CaaX protein substrate.
      Individual expression of each gene yielded no activity; however, co-expression of
      the two genes resulted in high levels of [3H] geranylgeranyl incorporation into
      the substrate protein Ras-Cys-Val-Val-Leu. The activity was partially purified
      yielding approximately 12,600 units/liter. The partially purified enzyme
      geranylgeranylated the Ras-Cys-Val-Val-Leu, Ras-Cys-Ala-Ile-Leu, Ras-Cys-Ile-Ile
      Leu, and Ras-Cys-Thr-Ile-Leu substrates but not the Ras-Cys-Val-Leu-Ser or Ras
      Ser-Val-Leu-Ser substrates. The protein geranylgeranyltransferase was highly
      specific for geranylgeranyl diphosphate and poorly transferred farnesyl. The
      recombinant enzyme was indistinguishable from the native type I
      geranylgeranyltransferase in yeast extracts. As has been reported for the protein
      farnesyltransferase, the yeast type I protein geranylgeranyltransferase is also a
      magnesium-requiring, zinc metalloenzyme. Interestingly, the recombinant enzyme
      functioned with calcium as the only divalent cation, although addition of zinc
      increased calcium-dependent activity 2-fold.

PMID- 1400381
TI  - Phosphatidylethanolamine:dolichol acyltransferase. Characterization and partial
      purification of a novel rat liver enzyme.
AB  - Incubation of rat or human post-heparin plasma with [3H]dolichol incorporated in
      liposomes consisting of dioleoyl phosphatidylcholine:dioleoyl
      phosphatidylethanolamine (3:1) resulted in the formation of radioactive dolichyl
      oleate. Non-heparinized plasma did not esterify dolichol, and, hence, the enzyme
      involved is probably associated with the cell surface and released into the blood
      by heparin. The major location of this activity was the liver, and, therefore, a
      partial purification of the enzyme from heparinized rat liver perfusates was
      performed using DEAE-Sephacel and heparin-Sepharose chromatography. The dolichol
      acyltransferase activity copurified with hepatic lipase activity in a lipid
      protein complex of 350 kDa. Optimal acylation is achieved at pH 7.5 in the
      presence of 5% plasma and 20 mM Ca2+. Esterification can only be obtained when
      dolichol is present in a phospholipid bilayer, and the reaction is strongly
      stimulated by unsaturated phosphatidylethanolamine or phosphatidylserine.
      Radiolabeling experiments demonstrated that the primary acyl donor is
      phosphatidylethanolamine from which the fatty acid is transferred exclusively
      from position 1. Neither cholesterol nor retinol are esterified by the enzyme,
      and the reaction is not stimulated by acyl-CoA. Both the extracellular
      localization and the mechanism of transacylation clearly distinguish this new
      enzyme from the acyl-CoA:dolichol acyltransferase described earlier in
      microsomes.

PMID- 1400382
TI  - Site-directed mutagenesis at the active site of Escherichia coli TEM-1 beta
      lactamase. Suicide inhibitor-resistant mutants reveal the role of arginine 244
      and methionine 69 in catalysis.
AB  - Arginine 244 is a highly conserved residue in Class A beta-lactamases, while
      methionine 69 is not. Informational suppression experiments show that replacement
      of M69 by a leucine, or that of R244 by most other amino acids lead to clavulanic
      acid-resistant phenotypes. The arginyl 244 side chain is tightly held in a
      network of interactions within the active site. Its replacement by a glutamine or
      a threonine perturbs the enzyme kinetics but to a smaller extent than would have
      been predicted if it were directly involved in substrate binding. Clavulanic acid
      and sulbactam still interact specifically with the mutant enzymes but are much
      less efficiently metabolized. Substitutions at position 244 also unveil
      interactions between the C6 substituent of substrates and the Asn132/Glu104
      region of the active site. Methionine 69 is located in a region of strong
      structural constraints and presents an unusual conformation. Molecular dynamics
      simulation showed that its replacement by a leucine does not release the strain
      in this area and induces only minor structural changes. Accordingly, the kinetic
      behavior of the mutant is only marginally perturbed, except for suicide
      inhibitors. Both clavulanic acid and sulbactam are well degraded by the mutant
      enzyme, while irreversible inactivation is dramatically decreased. The
      contribution of both residues to catalysis is discussed in the light of the
      kinetic and structural data.

PMID- 1400383
TI  - Isolation and partial characterization of lumican and decorin from adult chicken
      corneas. A keratan sulfate-containing isoform of decorin is developmentally
      regulated.
AB  - The proteoglycans extracted from adult chicken were initially purified by DEAE
      chromatography. Digestion of these proteoglycans with chondroitinase ABC
      generated a single 40-kDa core protein while digestion with keratanase generated
      a single 52-kDa core protein. Digestion with both enzymes combined, however,
      increased the amount of 40-kDa core protein produced. This suggested that the 40
      kDa core protein exists with chondroitin/dermatan sulfate (C/DS) side chains
      alone and with both C/DS and keratan sulfate (KS) side chains. The proteoglycan
      fraction was initially digested with chondroitinase ABC, and the M(r) = 40,000
      core protein derived from proteoglycans containing C/DS side chains alone was
      isolated. Amino-terminal sequencing showed it to be the chick cognate of decorin.
      The remaining proteoglycans were then digested with keratanase, and both the 40
      kDa core protein and the 52-kDa core proteins derived from KS-containing
      proteoglycans were purified. The M(r) = 40,000 core protein derived from
      proteoglycans containing both C/DS and KS side chains had the same amino-terminal
      sequence as decorin and cross-reacted with antibodies to decorin. Sequence from
      the 52-kDa core protein derived from KS-containing proteoglycans showed it to be
      lumican. The results of this study suggest that adult chick corneas contain two
      isoforms of decorin: one containing C/DS side chains and the other, a hybrid,
      containing both C/DS and KS side chains. Embryonic corneas did not contain the
      hybrid isoform of decorin. These results suggest that different post
      translational modifications occur to the decorin gene product during corneal
      development and maturation.

PMID- 1400384
TI  - Biochemical basis of the constitutive repressor cleavage activity of recA730
      protein. A comparison to recA441 and recA803 proteins.
AB  - The recA730 mutation results in constitutive SOS and prophage induction. We
      examined biochemical properties of recA730 protein in an effort to explain the
      constitutive activity observed in recA730 strains. We find that recA730 protein
      is more proficient than the wild-type recA protein in the competition with single
      stranded DNA binding protein (SSB protein) for single-stranded DNA (ssDNA)
      binding sites. Because an increased aptitude in the competition with SSB protein
      has been previously reported for recA441 protein and recA803 protein, we directly
      compared their in vitro activities with those of recA730 protein. At low
      magnesium ion concentration, both ATP hydrolysis and lexA protein cleavage
      experiments demonstrate that these recA proteins displace SSB protein from ssDNA
      in a manner consistent with their in vivo repressor cleavage activity, i.e.
      recA730 protein > recA441 protein > recA803 protein > recAwt protein.
      Additionally, a correlation exists between the proficiency of the recA proteins
      in SSB protein displacement and their rate of association with ssDNA. We propose
      that an increased rate of association with ssDNA allows recA730 protein to
      displace SSB protein from the ssDNA that occurs naturally in Escherichia coli and
      thereby to become activated for the repressor cleavage that leads to SOS
      induction. RecA441 protein is similarly activated for repressor cleavage;
      however, in this case, significant SSB protein displacement occurs only at
      elevated temperature. At physiological magnesium ion concentration, we argue that
      recA803 protein and wild-type recA protein do not displace sufficient SSB protein
      from ssDNA to constitutively induce the SOS response.

PMID- 1400385
TI  - Accumulation of a light-harvesting chlorophyll a/b protein in the chloroplast
      grana lamellae. The lateral migration of the membrane protein precursor is
      independent of its processing.
AB  - The events that follow the import of pLHCPIIb, the apoprotein precursor of the
      major light-harvesting complex of photosystem II, were studied in intact pea
      chloroplasts. The distribution of the events of insertion into the membrane, and
      processing, to yield the mature form (LHCP) between stromal and granal lamellae
      regions of the thylakoids were followed. pLHCP was preferentially inserted into
      stromal lamellae (SL) from which it migrated to granal lamellae (GL). Migration
      occurred before or after processing, suggesting that migration and processing are
      independent of each other. When migration was slowed down, LHCP accumulated in
      SL. Prolonged inhibition of migration induced degradation of LHCP that had
      accumulated in SL, whereas inhibition of processing did not affect the migration
      of pLHCP into GL. A small difference in electrophoretic mobility was noted
      between LHCP in SL and in GL. The predominant mature form in SL migrated more
      slowly than LHCP from GL. When thylakoids were subjected to trypsin, all of the
      LHCP embedded in SL underwent cleavage, whereas up to 60% of the radioactive LHCP
      in GL was resistant to the enzyme. The possible implications of the differences
      in size and in the sensitivity to trypsin of LHCP are discussed.

PMID- 1400386
TI  - Degradation of secretory immunoglobulin M in B lymphocytes occurs in a
      postendoplasmic reticulum compartment and is mediated by a cysteine protease.
AB  - In 38C B lymphocytes, membrane IgM is expressed on the surface, whereas secretory
      IgM (sIgM) is rapidly degraded. Here, we localize this degradation and
      characterize the proteases involved in this process. Upon treatment with
      brefeldin A, degradation of sIgM in 38C cells was strongly inhibited, as was
      secretion from the sIgM-secreting D2 hybridoma. Moreover, the brefeldin A-induced
      Golgi resorption resulted in galactosylation of sIgM and partial resistance to
      endoglycosidase H. However, sIgM avoided degradation neither due to modified
      terminal glycosylation nor as a consequence of the brefeldin A-induced altered
      milieu of the endoplasmic reticulum. When these modifications were prevented by
      inhibiting retrograde transport with nocodazole or by abrogating terminal
      glycosylation with swainsonine, sIgM was still rescued from degradation. The
      unaffected breakdown in the presence of nocodazole also argued against recycling
      of sIgM to be degraded in the endoplasmic reticulum. Furthermore, upon removal of
      brefeldin A, degradation of galactosylated sIgM resumed in 38C cells, as did
      secretion from D2 cells. These results indicate that functional export of
      proteins from the endoplasmic reticulum is a prerequisite for sIgM degradation.
      Biochemical characterization of this novel postendoplasmic reticulum/pre-trans
      Golgi proteolytic pathway included application of inhibitors to a broad spectrum
      of proteases. Among the compounds tested, only calpain inhibitor I exerted strong
      inhibition. The involvement of cysteine protease(s) in the degradation of sIgM
      was corroborated by the inhibitory effect of diamide. We conclude that B
      lymphocytes avoid secretion by active and selective targeting of sIgM to a
      developmentally regulated postendoplasmic reticulum degradation pathway in which
      degradation is mediated by a cysteine protease.

PMID- 1400387
TI  - Purification and characterization of the periplasmic lysine-, arginine-,
      ornithine-binding protein (LAO) from Salmonella typhimurium.
AB  - The lysine-, arginine-, ornithine-binding protein (LAO) from Salmonella
      typhimurium has been purified to homogeneity and characterized. The dissociation
      constants (KD) were determined by equilibrium dialysis assay to be 14, 15, and 29
      nM for L-arginine, L-lysine, and L-ornithine respectively. L-Histidine was found
      to be a relatively good ligand (KD, 500 nM). Methods have been developed for the
      separation of liganded from unliganded LAO, for the estimation of bound ligand,
      and for unliganding LAO. Liganded and unliganded LAO are shown to have distinct
      UV spectra. The UV spectrum also varies with the nature of the substrate.
      Inhibition studies with substrate analogs yielded information useful for
      understanding the nature of the ligand-binding pocket.

PMID- 1400388
TI  - Influence of membrane potential changes on cytoplasmic Ca2+ concentration in an
      electrically excitable cell, the insulin-secreting pancreatic B-cell.
AB  - Glucose stimulation of insulin release involves metabolism of the sugar and
      elevation of cytoplasmic calcium (Ca2+i) in pancreatic B-cells. We compared the
      dynamic changes of metabolism (fluorescence of endogenous reduced pyridine
      nucleotides, NAD(P)H), membrane potential (intracellular microelectrodes), and
      Ca2+i (fura-2 technique), in intact mouse islets. Glucose (15 mM) sequentially
      triggered an increase in NAD(P)H fluorescence, a depolarization with electrical
      activity, and a rise in Ca2+i. The change in NAD(P)H was monophasic and regular,
      whereas the changes in membrane potential and Ca2+i were multiphasic, with steady
      state regular oscillations of similar average frequencies (about 2.2/min).
      Digital image analysis revealed that Ca2+i oscillations were synchronous in all
      regions of the islets. Omission of extracellular Ca2+ abolished the rise in Ca2+i
      but not the increase in NAD(P)H. Both electrical and Ca2+i oscillations
      disappeared in low external Ca2+ (1 mM), and became larger but slower in high
      Ca2+ (10 mM). Sustained depolarization (by tolbutamide, arginine, or high K+) and
      hyperpolarization (by diazoxide) of B-cells caused sustained increases and
      decreases of Ca2+i, respectively. In conclusion, the changes in membrane
      potential induced by various secretagogues trigger synchronous changes in Ca2+i
      in all B-cells of the islets. The oscillatory pattern of the electrical and Ca2+i
      responses induced by glucose is not accompanied by and thus probably not due to
      similar oscillations of metabolism.

PMID- 1400389
TI  - Angiotensin II stimulates glucose transport activity in cultured vascular smooth
      muscle cells.
AB  - The glucose transport system in cultured rat vascular smooth muscle cells has
      been examined by measuring the uptake of 2-deoxyglucose. Angiotensin II (Ang II)
      stimulated 2-deoxyglucose uptake in cells made quiescent by removing serum from
      the culture medium in a dose- and time-dependent manner that was shown to be
      receptor-mediated. Epidermal growth factor (EGF), fetal calf serum, thrombin, and
      arginine vasopressin also stimulated glucose transport. Cycloheximide did not
      affect the immediate-early (30 min) activation by either Ang II or EGF, but
      abolished any further increase. This suggested that, whereas the initial
      activation of glucose transport was independent of protein synthesis, the
      sustained increase required the synthesis of new glucose transporters. This was
      supported by 4-fold and 2-fold accumulations of GLUT-1 mRNA 4 h after exposure to
      Ang II and EGF, respectively. The induction of GLUT-1 mRNA was preceded by rapid
      and transient expression of c-fos and c-jun protooncogenes. In nuclear run-on
      assays, nuclei from Ang II-treated cells showed increased synthesis of GLUT-1
      mRNA at 30 min and 1 h after hormone treatment. In contrast, in cells exposed to
      actinomycin D, pretreatment with Ang II had no effect on the turnover rates of
      GLUT-1 mRNa. These results are consistent with Ang II acting to stimulate the
      rate of transcription of the GLUT-1 gene leading to increased production of GLUT
      1 protein and glucose transport.

PMID- 1400390
TI  - Nitrilase from Rhodococcus rhodochrous J1. Sequencing and overexpression of the
      gene and identification of an essential cysteine residue.
AB  - The amino acid sequences of the NH2 terminus and internal peptide fragments of a
      Rhodococcus rhodochrous J1 nitrilase were determined to prepare synthetic
      oligonucleotides as primers for the polymerase chain reaction. A 750-base DNA
      fragment thus amplified was used as the probe to clone a 5.4-kilobase PstI
      fragment coding for the whole nitrilase. The nitrilase gene modified in the
      sequence upstream from the presumed ATG start codon was expressed to
      approximately 50% of the total soluble protein in Escherichia coli. The predicted
      amino acid sequence of the nitrilase gene showed similarity to that of the
      bromoxynil nitrilase from Klebsiella ozaenae. The 5,5'-dithiobis(2-nitrobenzoic
      acid) modification of the nitrilase from R. rhodochrous J1 resulted in
      inactivation with the loss of one sulfhydryl group/enzyme subunit. Of 4 cysteine
      residues in the Rhodococcus nitrilase, only Cys-165 is conserved in the
      Klebsiella nitrilase. Mutant enzymes containing Ala or Ser instead of Cys-165 did
      not exhibit nitrilase activity. These findings suggest that Cys-165 plays an
      essential role in the function of the active site.

PMID- 1400392
TI  - Possible salt bridges between transmembrane alpha-helices of the lactose carrier
      of Escherichia coli.
AB  - Although it is energetically extremely unfavorable to have charged amino acid
      residues of a polypeptide in the hydrophobic environment of the membrane
      phospholipid bilayer, a few such charged residues are found in membrane-spanning
      regions of membrane proteins. Ion pairs (salt bridges) would be much more stable
      in low dielectric media than single ionized residues. This paper provides
      indirect evidence for a salt bridge between Asp-240 and Lys-319 in the lactose
      carrier of Escherichia coli. When Asp-240 was changed to alanine by site-directed
      mutagenesis, there was a loss of the ability to accumulate methyl-beta-D
      thiogalactopyranoside (TMG), melibiose, or lactose. Fast-growing revertants were
      isolated on melibiose minimal agar plates. Two second-site revertants were
      isolated: Asp-240-->Ala plus Gly-268-->Val and Asp-240-->Ala plus Lys-319-->Gln.
      These revertants showed extremely poor accumulation of TMG, melibiose, and
      lactose, but showed significant "downhill" lactose entry into beta-galactosidase
      containing cells with sugar concentrations of 2 and 5 mM. It is concluded that
      there is some important interaction between Asp-240 and Lys-319, possibly a salt
      bridge.

PMID- 1400391
TI  - Regulation of collagenase gene expression by serotonin and progesterone in rat
      uterine smooth muscle cells.
AB  - The regulation of collagenase gene expression by serotonin and progesterone was
      investigated in primary cultures of rat uterine smooth muscle cells. Northern
      blot analysis demonstrates that serotonin (5-hydroxytryptamine (5-HT)), when
      administered to cells in serotonin-depleted medium, causes 6-8-fold increases in
      levels of collagenase mRNA. Selective serotonin 5-HT2 receptor agonists were able
      to mimic the effect of the natural hormone, while the induction by serotonin
      could be blocked by 5-HT2 receptor antagonists. Addition of phorbol ester (PMA)
      to 5-HT-depleted cultures fully mimicked the effect of 5-HT on collagenase mRNA
      induction. Treatment with progesterone analogs caused a decrease in collagenase
      mRNA, even in the presence of saturating levels of serotonin or PMA. In all
      experiments, levels of secreted collagenase were observed to correspond to levels
      of collagenase mRNA. Experiments with cycloheximide demonstrate that serotonin-
      and PMA-induced increases in collagenase mRNA are dependent on protein synthesis.
      Furthermore, nuclear run-on analysis shows that mRNA increases are accompanied by
      increases in initiation of transcripts. These data indicate that transcription of
      collagenase mRNA in myometrial smooth muscle cells is stimulated by serotonin,
      possibly via activation of protein kinase C, but is in some way prevented by the
      negative influence of progesterone.

PMID- 1400393
TI  - Regulation of iron uptake in Saccharomyces cerevisiae. The ferrireductase and
      Fe(II) transporter are regulated independently.
AB  - Iron is required for the growth of Saccharomyces cerevisiae. High concentrations
      of iron, however, are toxic, forcing this yeast to tightly regulate its
      concentration of intracellular free iron. We demonstrate that S. cerevisiae
      accumulates iron through the combined action of a plasma membrane ferrireductase
      and an Fe(II) transporter. This transporter is highly selective for Fe(II).
      Several other transition metals did not inhibit iron uptake when these metals
      were present at a concentration 100-fold higher than the Km (0.15 microM) for
      iron transport. Pt(II) inhibited ferrireductase activity but not the ability of
      cells to transport iron that was chemically reduced to Fe(II). Incubation of
      cells in a synthetic iron-limited media resulted in the induction of both
      ferrireductase and Fe(II) transporter activities. In complex media, Fe(II)
      transport activity was regulated in response to media iron concentration, while
      the activity of the ferrireductase was not. When stationary phase cells were
      inoculated into fresh media, ferrireductase activity increased independent of the
      iron content of the media; in contrast, transporter activity varied inversely
      with iron levels. These results demonstrate that the ferrireductase and Fe(II)
      transporter are separately regulated and that iron accumulation may be limited by
      changes in either activity.

PMID- 1400394
TI  - Protein changes associated with reprotonation of the Schiff base in the
      photocycle of Asp96-->Asn bacteriorhodopsin. The MN intermediate with
      unprotonated Schiff base but N-like protein structure.
AB  - The difference Fourier transform infrared spectrum for the N intermediate in the
      photoreaction of the light-adapted form of bacteriorhodopsin can be recorded at
      pH 10 at 274 K (Pfefferle, J.-M., Maeda, A., Sasaki, J., and Yoshizawa, T. (1991)
      Biochemistry 30, 6548-6556). Under these conditions, Asp96-->Asn
      bacteriorhodopsin gives a photoproduct which shows changes in protein structure
      similar to those observed in N of wild-type bacteriorhodopsin. However, decreased
      intensity of the chromophore bands and the single absorbance maximum at about 400
      nm indicate that the Schiff base is unprotonated, as in the M intermediate. This
      photoproduct was named MN. At pH 7, where the supply of proton is not as
      restricted as at pH 10, Asp96-->Asn bacteriorhodopsin yields N with a protonated
      Schiff base. The Asn96 residue, which cannot deprotonate as Asp96 in wild-type
      bacteriorhodopsin, is perturbed upon formation of both MN at pH 10 and N at pH 7.
      We suggest that the reprotonation of the Schiff base is preceded by a large
      change in the protein structure including perturbation of the residue at position
      96.

PMID- 1400395
TI  - Stimulation and inhibition of human platelet adenylylcyclase by
      thiophosphorylated transducin beta gamma-subunits.
AB  - The effect of beta gamma-dimers isolated from the retinal guanine nucleotide
      binding protein (G protein) transducin eluted from illuminated bovine rod outer
      segment membranes with GTP, guanosine 5'-O-(beta, gamma-imino)triphosphate
      (Gpp(NH)p), or guanosine 5'-O-(gamma-thio)triphosphate (GTP gamma S) on basal and
      forskolin-stimulated adenylylcyclase activities in membranes of human platelets
      was studied. beta gamma-Subunits isolated from transducin eluted with GTP gamma S
      (TD beta gamma GTP gamma S) had a concentration-dependent stimulatory effect on
      basal adenylylcyclase activity. The stimulatory agonist prostaglandin E1
      increased the potency and the maximum extent of stimulation due to TD beta gamma
      GTP gamma S). With a similar concentration dependence, TD beta gamma GTP gamma S
      exerted an inhibitory influence on forskolin-stimulated adenylylcyclase activity.
      At the same concentrations, beta gamma-dimers isolated with either GTP or
      Gpp(NH)p did not alter enzyme activities. The observed effects of TD beta gamma
      GTP gamma S were similar to those of directly added GTP gamma S with regard to
      maximum levels, time dependence, and persistence; however, TD beta gamma GTP
      gamma S was approximately 10-fold more potent than GTP gamma S. Treatment of TD
      beta gamma GTP gamma S, but not of free GTP gamma S, with hydroxylamine caused a
      loss of adenylylcyclase regulation by TD beta gamma GTP gamma S. The data
      presented indicated that TD beta gamma GTP gamma S potently and efficiently
      activates the stimulatory and inhibitory G proteins of adenylylcyclase in human
      platelet membranes. Furthermore, evidence is provided suggesting that the
      observed effects of TD beta gamma GTP gamma S, which can be thiophosphorylated by
      GTP gamma S at the beta-subunit (Wieland, T., Ulibarri, I., Gierschik, P., and
      Jakobs, K. H. (1991) Eur. J. Biochem. 196, 707-716), are due to formation of GTP
      gamma S at the G proteins.

PMID- 1400396
TI  - Cloning and characterization of the major promoter of the human protein kinase C
      beta gene. Regulation by phorbol esters.
AB  - The expression of the beta isoenzyme for protein kinase C is regulated
      developmentally and in response to inducers of cell differentiation (such as
      phorbol esters and 1 alpha,25-dihydroxyvitamin D3). The 5' segment of the gene
      for protein kinase C beta was cloned from a human leukocyte genomic library in
      EMBL3 bacteriophage. This segment of the gene (greater than 54 kilobases in
      length) encompassed the coding sequence for the amino-terminal regulatory domain
      of the enzyme, the 5'-untranslated region, and the 5'-flanking region. Initiation
      of transcription was identified by S1 nuclease analysis and confirmed by RNase
      protection analysis at 197 base pairs 5' of the initiator ATG. Sequence analysis
      of the 5'-flanking region revealed it to be extremely G+C-rich (> 80%) with many
      features of a CpG island. Comparison of sequence with known cis-regulatory motifs
      disclosed a number of potential regulatory elements including an octamer binding
      motif at -76, Sp1-binding sites at -94 and -63, E boxes at -110, -26, and +18, an
      AP-1 site at -442, and an AP-2 site at -330. To demonstrate promoter activity, a
      630-base pair fragment extending from -587 to +43 was subcloned in front of a
      promoterless luciferase gene. This fragment was able to drive the expression of
      luciferase in transient transfections of human hematopoietic cells. Deletion
      analysis demonstrated that a fragment -111 to +43 was necessary and sufficient
      for promoter activity; this fragment did not contain TATA or CAAT motifs. The
      promoter was stimulated 8-20-fold by phorbol esters accounting for the previously
      observed transcriptional activation of protein kinase C beta. This phorbol ester
      responsiveness was conferred by the basal promoter (-111 to +43) and was
      independent of the AP-1 site. These results define a novel mechanism of protein
      kinase C autoregulation at a transcriptional level.

PMID- 1400397
TI  - Role of essential sulfhydryl groups in drug interactions at the neuronal 5-HT
      transporter. Differences between amphetamines and 5-HT uptake inhibitors.
AB  - The sulfhydryl-selective alkylating agent, N-ethylmaleimide (NEM), has been used
      as a tool to discern whether different binding domains exist on the neuronal
      serotonin (5-HT) transporter for 5-HT and 5-HT uptake inhibitors (Reith, M. E.
      A., Allen, D. L., Sershen, H., and Lajtha, A. (1984) J. Neurochem. 43, 249-255;
      Graham, D., Esnaud, H., Habert, E., and Langer, S. Z. (1989) Biochem. Pharmacol.
      38, 3819-3826). However, relatively high concentrations of NEM and long
      incubation times have been required for inactivation of the transporter-binding
      site which raises the possibility that NEM is reacting with other nucleophilic
      groups (Smyth, D. G., Blumenfeld, O. O., and Konigsberg, W. (1964) Biochem. J.
      91, 589-595). In the present work, the reactivity and essential nature of
      sulfhydryl groups associated with substrate/inhibitor binding to the neuronal 5
      HT transporter was assessed. [3H]Paroxetine, a potent and selective 5-HT uptake
      inhibitor, was used to label the 5-HT transporter. The effects of a relatively
      wide range of sulfhydryl reagents on [3H]paroxetine binding in
      digitoninsolubilized preparations of rat brain neuronal membranes and the
      relative abilities of different classes of drugs to protect against NEM-induced
      inactivation of [3H]paroxetine binding were studied. It was observed that
      digitonin-solubilized preparations were more sensitive than membrane preparations
      to the inactivating effects of NEM. The pKa of the reactive group was estimated
      to be 6.17, in the range expected for a reactive sulfhydryl. Sulfhydryls
      essential to ligand binding reacted preferentially with hydrophobic compounds (p
      hydroxymercuribenzoate = dithiobisnitrobenzoate > methyl methanethiosulfonate > N
      phenylmaleimide > N-ethylmaleimide) and were unreactive toward hydrophilic
      reagents such as iodoacetate and iodoacetamide. 5-HT, 5-HT uptake inhibitors and
      cocaine protected the digitonin-solubilized transporter from NEM-induced
      inactivation while the amphetamine-related releasing agents p-chloroamphetamine
      and fenfluramine were ineffective. The observation that the binding of some, but
      not all, ligands requires reduced sulfhydryl groups, suggests that differential
      mechanisms and/or different binding domains do exist for agents which interact at
      the neuronal 5-HT transporter.

PMID- 1400398
TI  - F0F1-ATPase gamma subunit mutations perturb the coupling between catalysis and
      transport.
AB  - We introduced mutations to test the function of the conserved amino-terminal
      region of the gamma subunit from the Escherichia coli ATP synthase (F0F1-ATPase).
      Plasmid-borne mutant genes were expressed in an uncG strain which is deficient
      for the gamma subunit (gamma Gln-14-->end). Most of the changes, which were
      between gamma Ile-19 and gamma Lys-33, gamma Asp-83 and gamma Cys-87, or at gamma
      Asp-165, had little effect on growth by oxidative phosphorylation, membrane
      ATPase activity, or H+ pumping. Notable exceptions were gamma Met-23-->Arg or Lys
      mutations. Strains carrying these mutations grew only very slowly by oxidative
      phosphorylation. Membranes prepared from the strains had substantial levels of
      ATPase activity, 100% compared with wild type for gamma Arg-23 and 65% for gamma
      Lys-23, but formed only 32 and 17%, respectively, of the electrochemical gradient
      of protons. In contrast, other mutant enzymes with similar ATPase activities
      (including gamma Met-23-->Asp or Glu) formed H+ gradients like the wild type.
      Membranes from the gamma Arg-23 and gamma Lys-23 mutants were not passively leaky
      to protons and had functional F0 sectors. These results suggested that
      substitution by positively charged side chains at position 23 perturbed the
      energy coupling. The catalytic sites of the mutant enzymes were still regulated
      by the electrochemical H+ gradient but were inefficiently coupled to H+
      translocation in both ATP-dependent H+ pumping and delta mu H+ driven ATP
      synthesis.

PMID- 1400399
TI  - Intraluminal Ca2+ dependence of Ca2+ and ryanodine-mediated regulation of
      skeletal muscle sarcoplasmic reticulum Ca2+ release.
AB  - The action of ryanodine upon sarcoplasmic reticulum (SR) Ca2+ handling is
      controversial with evidence for both activation and inhibition of SR Ca2+
      release. In this study, the role of the intraluminal SR Ca2+ load was probed as a
      potential regulator of ryanodine-mediated effects upon SR Ca2+ release. Through
      dual-wavelength spectroscopy of Ca2+:antipyrylazo III difference absorbance, the
      intraluminal Ca2+ dependence of ryanodine and Ca(2+)-induced Ca2+ release (CICR)
      from skeletal SR vesicles was examined. Ryanodine addition after initiation of
      Ca2+ uptake (a) increased the intraluminal Ca2+ sensitivity of CICR and (b)
      stimulated spontaneous Ca2+ release with a delayed onset. These ryanodine effects
      were inversely proportional to the intraluminal Ca2+ load. Ryanodine also
      inhibited subsequent CICR after reaccumulation of Ca2+ released from the initial
      CICR. These results provide evidence that ryanodine inhibits transitions between
      low and high affinity Ca2+ binding states of an intraluminal Ca2+ compartment,
      possibly calsequestrin. Conformational transitions of calsequestrin may be
      reciprocally coupled to transitions between open and closed states of the Ca2+
      release channel.

PMID- 1400400
TI  - Calcium-activated neutral protease effects upon skeletal muscle sarcoplasmic
      reticulum protein structure and calcium release.
AB  - In this study, the effects of Ca(2+)-activated neutral protease (CANP) upon
      skeletal muscle heavy sarcoplasmic reticulum (HSR) structure and function were
      investigated. CANP was immunolocalized to the 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonic acid detergent-insoluble
      fraction of purified HSR membranes. Ca2+ activation of the endogenous membrane
      bound CANP produced a characteristic partial fragmentation of the HSR 565-kDa
      Ca2+ release channel. Similarly, the major substrate for both micromolar and
      millimolar Ca(2+)-sensitive isoforms of exogenous CANP was the Ca2+ release
      channel with proteolysis of a 88-kDa HSR protein also observed. Ca2+ release
      channel proteolysis was initiated at a single cleavage site with coincidental
      production of 410- and 150-kDa peptide fragments. Appearance of 160- and 137-kDa
      limiting peptides accompanied secondary proteolysis of the primary 410- and 150
      kDa fragments, respectively. Despite extensive proteolysis of the Ca2+ release
      channel, CANP did not dramatically alter the Ca2+ handling and ryanodine binding
      properties of HSR membranes. The association of CANP with isolated HSR membranes
      suggests that, in vivo, this protease may modify an additional property of the
      Ca2+ release channel. This may be related to the CANP-susceptible structural
      association of the Ca2+ release channel with dihydropyridine receptors at T
      tubule/sarcoplasmic reticulum junctions.

PMID- 1400401
TI  - Cloning of human AMP deaminase isoform E cDNAs. Evidence for a third AMPD gene
      exhibiting alternatively spliced 5'-exons.
AB  - Higher eukaryotes express multiple isoforms of AMP deaminase (EC 3.5.4.6). In
      humans, four AMP deaminase variants, termed M (muscle), L (liver), E1, and E2
      (erythrocyte) can be distinguished by a variety of biochemical and immunological
      criteria. Previous molecular studies have reported two genes, AMPD1 and AMPD2,
      that produce isoform M and L transcripts, respectively. This study identifies a
      third human AMP deaminase gene, AMPD3. Nucleotide sequence alignments between
      AMPD3 cDNAs isolated from several human libraries indicate three different
      extreme 5'-ends. Alternate forms of the AMPD3 cDNAs contain a common 2301-bp open
      reading frame (ORF) and 3'-untranslated region of 1245 bp. Two of the three
      forms, however, exhibit additional 5'-end nucleotide sequences that would extend
      their respective ORFs by 21 and 27 nucleotides. RNase protection analyses and the
      partial characterization of human AMPD3 genomic clones demonstrate alternative
      splicing of three different 5'-terminal exons. Western blot analyses detect anti
      E-specific immunoreactivity in affinity-purified extracts derived from the
      bacterial expression of a truncated AMPD3 cDNA. These results are discussed in
      relation to AMP deaminase isoform diversity.

PMID- 1400402
TI  - Differential irreversible insertion of protein kinase C into phospholipid
      vesicles by phorbol esters and related activators.
AB  - Incubation of protein kinase C (PKC) alpha with phorbol 12,13-dibutyrate and
      phospholipid vesicles promoted a time-dependent irreversible insertion of the
      enzyme into the vesicles and the generation of a calcium-independent kinase
      activity. Calcium neither caused insertion nor influenced the insertion induced
      by the phorbol ester. The effect was strongly dependent on the phosphatidylserine
      concentration in the vesicle and could also be supported by other anionic
      phospholipids. An analysis of the structure-activity relations of PKC activators
      for the calcium-independent kinase activity revealed marked relative differences
      in potencies for binding and for insertion. Compounds such as phorbol 13
      myristate 12-acetate and mezerein were very efficient at inducing insertion. In
      contrast, 12-deoxyphorbol esters and diacylglycerol were relatively inefficient
      at inducing insertion, requiring higher concentrations than expected from their
      binding affinities. The insertion of PKC alpha depended substantially on the
      length of the aliphatic esters in the 12- and 13-positions of the phorbol
      derivatives, and once again, potencies for insertion and binding were not
      directly proportional. Our findings suggest two different sites for ligand
      interaction on the molecule of PKC alpha with different structure-activity
      requirements. We speculate that the differential ability of compounds to promote
      insertion could contribute to the documented marked differences in the biological
      behavior of PKC activators.

PMID- 1400404
TI  - Regulation of the actin-activated ATPase and in vitro motility activities of
      monomeric and filamentous Acanthamoeba myosin II.
AB  - The actin-activated Mg(2+)-ATPase activity of filamentous Acanthamoeba myosin II
      is inhibited by phosphorylation of 3 serine residues at the tip of the tail of
      each heavy chain. From previous studies, it had been concluded that the activity
      of each molecule in the filament was regulated by the global state of
      phosphorylation of the filament and was independent of its own phosphorylation
      state. The actin-activated Mg(2+)-ATPase activity of monomeric phosphorylated
      myosin II was not known because it polymerizes under the ionic conditions
      necessary for the expression of this activity. We have now found conditions to
      maintain myosin II monomeric and active during the enzyme assay. The actin
      activated Mg(2+)-ATPase activities of monomeric dephosphorylated and
      phosphorylated myosin II were found to be the same as the activity of filamentous
      dephosphorylated myosin II. These results support the conclusion that
      phosphorylation regulates filamentous myosin II by affecting filament
      conformation. Consistent with their equivalent enzymatic activities, monomeric
      and filamentous dephosphorylated myosin II were equally active in an in vitro
      motility assay in which myosin adsorbed to a surface drives the movement of F
      actin. In contrast to their very different enzymatic activities, however,
      filamentous and monomeric phosphorylated myosin II had similar activities in the
      in vitro motility assay; both were much less active than monomeric and
      filamentous dephosphorylated myosin II. One interpretation of these results is
      that the rate-limiting steps in the two assays are different and that, while the
      rate-limiting step for actin-activated Mg(2+)-ATPase activity is regulated only
      at the level of the filament, the rate-limiting step for motility can also be
      regulated at the level of the monomer.

PMID- 1400403
TI  - Central non-Pur.Pyr sequences in oligo(dG.dC) tracts and metal ions influence the
      formation of intramolecular DNA triplex isomers.
AB  - The effect of the central non-Pur.Pyr sequences in oligo(dG.dC) inserts on
      determining the type of intramolecular DNA triplex isomers formed in negatively
      supercoiled plasmids was investigated. Different triplex types (H-r3, H-r5, and H
      y3), revealed by a combination of chemical probing and Maxam-Gilbert sequencing
      reactions, were adopted by the oligo(dG.dC) tracts depending on the length and
      composition of the central non-Pur.Pyr sequences (0, 3, or 5 base pairs) and the
      kind of metal ions. The H-r3 triplex conformer, one isomer of a Pur.Pur.Pyr
      structure, was formed in the (C)20 and (C)10GCG(C)10 inserts in plasmids in the
      presence of certain metal ions. Interestingly, H-r5, the other isomer of the
      Pur.Pur-Pyr triplex which had not been detected previously, was formed in a
      (C)9GAATT(C)9 insert in the presence of either Mg2+ or Ca2+. Alternatively, H-y3,
      one isomer of a Pyr.Pur.Pyr triplex, was formed in the (C)9GAATT(C)9 insert in
      the absence of metal ions. Thus, central non-Pur.Pyr sequences and metal ions
      play a role as determinants of the types of intramolecular triplexes formed; they
      also reduce the requirement of longer Pur.Pyr repeat sequences to form
      intramolecular triplexes. Furthermore, the effects of MgCl2 concentration and pH
      on the formation of triplex isomers were examined. The Pur.Pur.Pyr conformations
      (H-r3 and H-r5) may be the favored conformations in the cellular milieu, since
      they are stable at physiological pH and metal ion concentration.

PMID- 1400405
TI  - Limited proteolysis reveals a structural difference in the globular head domains
      of dephosphorylated and phosphorylated Acanthamoeba myosin II.
AB  - Phosphorylation at three sites at the tip of the tail of myosin II from
      Acanthamoeba castellanii inactivates the actin-activated Mg(2+)-ATPase activity
      of filamentous myosin and the in vitro motility activity of both monomeric and
      filamentous myosin. To seek a structural explanation for these effects, we
      examined the susceptibilities of dephosphorylated and phosphorylated myosins II
      to endoproteinases. Endoproteinase Arg-C cleaved myosin II preferentially at two
      sites in the globular head, Lys-621 and Arg-638, producing an NH2-terminal
      fragment of about 67,000 Da and a COOH-terminal fragment of about 112,000 Da.
      Dephosphorylated monomers and filaments were cleaved about 3 times more rapidly
      than their phosphorylated counterparts principally because of a much greater rate
      of cleavage at Arg-638; the ratio of cleavage at Arg-638:Lys-621 was about 3 for
      dephosphorylated myosins and about 0.5 for phosphorylated myosins. These data
      demonstrate that phosphorylation at the tip of the tail of Acanthamoeba myosin II
      causes a conformational change in the globular head that contains the catalytic
      sites; therefore, this conformational change may be related to the different
      catalytic and motile activities of the dephosphorylated and phosphorylated
      enzymes.

PMID- 1400406
TI  - Purification, structure, and characterization of caltrin proteins from seminal
      vesicle of the rat and mouse.
AB  - Caltrins, small basic proteins that inhibit calcium uptake by epididymal
      spermatozoa, have been purified from seminal vesicle content of the mouse and
      rat. Mouse caltrin (M(r) 8,476) contains 75 amino acid residues, 14 basic, 5
      acidic, and 7 cysteines while rat caltrin (M(r) 6,217) has 56 residues, 10 basic,
      5 acidic, and 6 cysteines; their pI values are 10.2 and 9.3, respectively. The
      proteins did not react with Ellman's reagent unless the cystine residues were
      previously reduced. The primary structures were determined by sequencing
      fragments generated by trypsin, clostripain, and endoproteinase Lys-C digestion.
      The sequences were ordered to give the total structural formula. The two
      molecules have no sequence similarity and are different from those of the bull
      and guinea pig previously reported. Only rat caltrin has a sequence of 13
      residues nearly identical to that in guinea pig caltrin I. Both rat and mouse
      caltrin react with antibodies against bovine and guinea pig caltrins. Reduction
      and alkylation of cysteine residues suppressed the immunologic response of mouse
      caltrin; however, modified rat caltrin retained partially its immunoreactivity
      with the antiserum against guinea pig caltrin I. The same treatment abolished the
      calcium transport inhibitory activity of mouse caltrin and greatly reduced that
      of rat caltrin. It is likely that rat and mouse caltrins have the same
      physiological function as proposed for bovine caltrin; namely, to regulate the
      development of the Ca(2+)-dependent processes that "capacitate" sperm for
      fertilization.

PMID- 1400407
TI  - A rho gene product in human blood platelets. II. Effects of the ADP-ribosylation
      by botulinum C3 ADP-ribosyltransferase on platelet aggregation.
AB  - In the accompanying paper (Nemoto, Y., Namba, T., Teru-uchi, T., Ushikubi, F.,
      Morii, N., and Narumiya, S. (1992) J. Biol. Chem. 267, 20916-20920), we have
      identified rhoA protein as the sole substrate protein for botulinum C3 ADP
      ribosyltransferase (C3 exoenzyme) in human blood platelets. Here we examined the
      role of rhoA protein in platelet functions. C3 exoenzyme added to washed
      platelets dose- and time-dependently ADP-ribosylated rhoA protein in situ in the
      cells. Concomitant with this modification, inhibition of thrombin-induced
      platelet aggregation was observed. This inhibition was not reversed by washing
      the treated platelets, but was not found when C3 exoenzyme was pretreated with
      mouse monoclonal anti-C3 exoenzyme antibody. C3 exoenzyme treatment did not
      affect thrombin-induced inositol 1,4,5-trisphosphate production. Secretion of
      preloaded [14C]serotonin was delayed by the enzyme treatment, but the extent of
      the secretion was not influenced. In addition, the enzyme treatment did not
      change the expression of the glycoprotein IIb-IIIa complex on the platelet
      surface. The enzyme treatment also suppressed platelet aggregation induced by
      phorbol myristate acetate. These results suggest that rhoA protein plays a role
      mainly in the aggregation process downstream from receptor-phospholipase C
      coupling. This, together with the previous finding that rhoA protein modulates
      stress fiber formation in cultured fibroblasts (Paterson, H. F., Self, A. J.,
      Garrett, M. D., Just, I., Aktories, K., and Hall, A. (1990) J. Cell Biol. 111,
      1001-1007), suggests that rhoA protein regulates the assembly of actin filaments
      and the avidity of the platelet integrin (glycoprotein IIb-IIIa) in the
      aggregation process.

PMID- 1400408
TI  - Regulation of Hsp70 function by a eukaryotic DnaJ homolog.
AB  - We report that a purified cytoplasmic Hsp70 homolog from Saccharomyces
      cerevisiae, Hsp70SSA1, exhibits a weak ATPase activity, which is stimulated by a
      purified eukaryotic dnaJp homolog (YDJ1p). Stable complex formation between
      Hsp70SSA1 and the permanently unfolded protein carboxymethylated alpha
      lactalbumin (CMLA) was assayed by native gel electrophoresis. The affinity of
      Hsp70SSA1 for CMLA appeared to be regulated by YDJ1p. Significant reduction in
      both CMLA-Hsp70SSA1 complex formation and the release of CMLA pre-bound to
      Hsp70SSA1 was observed only in the presence of both YDJ1p and ATP. Thus,
      Hsp70SSA1 and YDJ1p interact functionally in the execution of Hsp70SSA1 chaperone
      activities in the eukaryotic cell.

PMID- 1400409
TI  - p13suc1 suppresses the catalytic function of p34cdc2 kinase for intermediate
      filament proteins, in vitro.
AB  - The regulation of p34cdc2 kinase activity controls the entry into and exit from
      mitosis. Although genetic and biochemical evidence suggested close interactions
      between cyclins, p13suc1 and p34cdc2 kinase, the roles of p13suc1 on p34cdc2
      kinase functions remain unclear. To examine the effects of p13suc1 on p34cdc2
      kinase function we developed a simple purification procedure for p34cdc2 kinase,
      unassociated with p13suc1. The key to the purification procedures we used was
      buffer containing 0.5 M NaCl and 50% ethylene glycol, as a specific elutant of
      p34cdc2 kinase from p13suc1-Sepharose. This purified p34cdc2 kinase
      stoichiometrically phosphorylated vimentin and desmin. Exogenous p13suc1
      suppressed the phosphorylation of these filament proteins by the kinase and
      prevented disassembly, although histone H1 phosphorylation was not affected.
      Peptide mapping analysis showed a similar extent of inhibition by p13suc1 for all
      five phosphorylation sites by p34cdc2 kinase of vimentin and desmin, hence these
      p13suc1-induced inhibitions are probably not site-specific. It thus appears that
      p13suc1 has a selective effect on the catalytic activity of p34cdc2 kinase for
      these filament proteins.

PMID- 1400410
TI  - TATA-binding protein activates transcription when upstream of a GCN4-binding site
      in a novel yeast promoter.
AB  - In the gal-his3 hybrid promoter, his3-GG1, GCN4 stimulates transcription at the
      position normally occupied by a TATA element. This expression requires two
      elements within gal1-10 sequences, a REB1-binding site and a second element, Z,
      which resides 20 base pairs upstream of the GCN4-binding site. No obvious TATA
      element is present in this promoter. To characterize the function of Z, we
      replaced it with short random oligonucleotides and selected for expression in
      vivo. Fourteen elements were identified and classified into groups based upon
      sequence and phenotypic similarities. Group 1 elements contained functional TATA
      sequences that were essential for activity. TATA elements can thus function when
      positioned upstream of a GCN4-binding site. The Group 2 elements activated
      transcription poorly when used as conventional TATA elements; however, mutational
      analyses demonstrated that their activity required TATA-like sequences. These
      TATA-like sequences bound the yeast TATA-binding protein (TBP) poorly in vitro
      but function in vivo as TBP interaction sites based upon two criteria. First
      mutations that improved their TATA character correspondingly improved function
      and second their activity could be enhanced in the presence of an altered binding
      specificity mutant of TBP. Furthermore, the Group 2 elements enabled the
      identification of mutations outside of the TATA-like core that contribute to
      transcriptional activation without adversely affecting TBP binding. The finding
      that low affinity TBP-binding sites can be used at unconventional positions
      suggests that many "TATA-less" promoters contain a cryptic interaction site for
      TBP.

PMID- 1400411
TI  - Human insulin-like growth factor I receptor 950tyrosine is required for
      somatotroph growth factor signal transduction.
AB  - Insulin-like growth factor I (IGF-I), a growth hormone (GH)-dependent growth
      factor exerts feedback regulation of GH by inhibiting GH gene expression. IGF-I
      inhibition of GH secretion is enhanced 3-5-fold in GC rat pituitary cells
      overexpressing the wild type 950Tyr human IGF-I receptor which autophosphorylates
      appropriately. To determine the critical amino acid sequence responsible for IGF
      I signaling, insertion, deletion, and site-directed mutants were constructed to
      substitute for 950Tyr in exon 16 of the human IGF-I receptor beta-subunit
      transmembrane domain. All mutant transfectants bound IGF-I with a similar Kd to
      untransfected cells but had markedly increased (7-34-fold) IGF-I-binding sites.
      GH responsiveness to IGF-I was tested in mutant transfectants. Overexpressed site
      directed and insertion mutant IGF-I receptors exhibited a modest suppressive
      effect on GH in response to the IGF-I ligand, similar to that observed in
      untransfected cells. Deletion mutant (IG-FIR delta 22) (amino acid 944-965) did
      not transduce the IGF-I signal to the GH gene. Site-directed and insertion
      mutants therefore did not enhance the IGF-I response of the endogenous rat
      receptor, unlike the 950Tyr wild type transfectants which enhanced the IGF-I
      signal. All mutant transfectants, except the deletion mutant, internalized
      radioactive ligand similarly to 950Tyr wild type transfectants. 950Tyr of the
      human IGF-I receptor is therefore required for IGF-I signal transduction in the
      pituitary somatotroph, but not for IGF-I-mediated internalization.

PMID- 1400412
TI  - Catalytic effectiveness of human aldose reductase. Critical role of C-terminal
      domain.
AB  - Human aldose reductase and aldehyde reductase are members of the aldo-keto
      reductase superfamily that share three domains of homology and a nonhomologous
      COOH-terminal region. The two enzymes catalyze the NADPH-dependent reduction of a
      wide variety of carbonyl compounds. To probe the function of the domains and
      investigate the basis for substrate specificity, we interchanged cDNA fragments
      encoding the NH2-terminal domains of aldose and aldehyde reductase. A chimeric
      enzyme (CH1, 317 residues) was constructed in which the first 71 residues of
      aldose reductase were replaced with first 73 residues of aldehyde reductase.
      Catalytic effectiveness (kcat/Km) of CH1 for the reduction of various substrates
      remained virtually identical to wild-type aldose reductase, changing a maximal 4
      fold. Deletion of the 13-residue COOH-terminal end of aldose reductase, yielded a
      mutant enzyme (AR delta 303-315) with markedly decreased catalytic effectiveness
      for uncharged substrates ranging from 80- to more than 600-fold (average 300
      fold). The KmNADPH of CH1 and AR delta 303-315 were nearly identical to that of
      the wild-type enzyme indicating that cofactor binding is unaffected. The
      truncated AR delta 303-315 displayed a NADPH/D isotope effect in kcat and an
      increased D(kcat/Km) value for DL-glyceraldehyde, suggesting that hydride
      transfer has become partially rate-limiting for the overall reaction. We conclude
      that the COOH-terminal domain of aldose reductase is crucial to the proper
      orientation of substrates in the active site.

PMID- 1400414
TI  - Functional analysis of nucleosome assembly protein, NAP-1. The negatively charged
      COOH-terminal region is not necessary for the intrinsic assembly activity.
AB  - A nucleosome assembly protein (NAP-1) of Saccharomyces cerevisiae facilitates the
      association of histones with DNA to form nucleosomes in vitro at physiological
      ionic conditions. The cloned gene was expressed in Escherichia coli using a T7
      expression system, and the protein (417 amino acid residues) was purified by Mono
      Q column chromatography. Various deletion fragments of NAP-1 protein were also
      produced, and their nucleosome assembly activity was examined by supercoiling
      assay. The internal fragment containing the residues 43-365 was necessary and
      sufficient for the activity, and a long stretch of negatively charged region near
      the carboxyl terminus was dispensable. This minimal size fragment could form the
      12 S NAP-1-histone complex as the whole protein could, whereas deleted fragments
      on either side could bind with core histones only to form aggregates.

PMID- 1400413
TI  - The Shaw-related potassium channel gene, Kv3.1, on human chromosome 11, encodes
      the type l K+ channel in T cells.
AB  - T lymphocytes exhibit three distinct types of voltage-gated K+ channels, n, n',
      and l, that are distributed in the T cell lineage according to subset, as well as
      the cells' activation and developmental status. Type l K+ channels are found
      sparingly in cytotoxic T cells from normal mice and abundantly in a specific T
      cell subset (CD4- CD8- Thy1+) from mice with autoimmune disease. Here, we show
      that the mouse Kv3.1 gene, when expressed in Xenopus oocytes, encodes a channel
      with properties remarkably similar to those of the l-type channel. Kv3.1
      transcripts were found in T cells isolated from the lymph nodes of MRL-lpr mice
      with systemic lupus erythematosus and in a human lymphoma cell line that also
      expresses the l channel phenotype. By these criteria, we conclude that Kv3.1
      encodes the voltage-gated type l K+ channel in lymphocytes. The Kv3.1 gene maps
      to human chromosome 11; the related Kv1.1 and Kv3.2 genes are localized on human
      chromosome 12, while the IsK gene maps to human chromosome 21.

PMID- 1400415
TI  - The muscle-derived lens of a squid bioluminescent organ is biochemically
      convergent with the ocular lens. Evidence for recruitment of aldehyde
      dehydrogenase as a predominant structural protein.
AB  - Many of the structural proteins of ocular lenses, commonly referred to as
      crystallins, are identical to specific enzymes or the result of a recent gene
      duplication (Piatigorsky, J., and Wistow, G. (1991) Science 252, 1078-1079). One
      such enzyme, aldehyde dehydrogenase (ALDH), has been recruited as a lens
      crystallin in certain mammals (Wistow, G., and Kim, H. (1991) J. Mol. Evol. 32,
      262-269) and cephalopods (Tomarev, S., Zinovieva, R., and Piatigorsky, J. (1991)
      J. Biol. Chem. 266, 24226-24231). We report here that a transparent tissue,
      derived from muscle but functioning as a lens in the light-emitting organ of a
      squid, Euprymna scolopes, shows striking biochemical convergence with the
      epidermally derived ocular lenses of some mammals and cephalopods. In the light
      organ lens of E. scolopes, an ALDH-like protein is the predominant molecular
      component. The typical muscle-specific proteins are replaced as the dominant
      species by a protein composed of 54-kDa subunits. This protein, which we
      designate as L-crystallin, constitutes approximately 70% of the total soluble
      protein of the light organ lens. The amino acid sequences of three peptides of L
      crystallin (approximately 9% of the total protein) showed 54.5% sequence identity
      with human cytosolic ALDH. Using polyclonal antiserum made against L-crystallin,
      we found that it is present in low abundance in other tissues of the squid,
      including muscle and the ocular lens. This polyclonal antiserum also cross
      reacted with the ALDH-like crystallins found in the ocular lenses of certain
      mammals and cephalopods. L-Crystallin showed no ALDH activity, which is similar
      to several other enzyme/crystallins, including ALDH/eta-crystallin (Wistow, G.,
      and Kim, H. (1991) J. Mol. Evol. 32, 262-269). The characteristics of this muscle
      derived lens are evidence that a common biochemical basis underlies transparency
      and that certain proteins may possess properties that promote their selection as
      lens structural proteins.

PMID- 1400416
TI  - Primary structure of Gal beta 1,3(4)GlcNAc alpha 2,3-sialyltransferase determined
      by mass spectrometry sequence analysis and molecular cloning. Evidence for a
      protein motif in the sialyltransferase gene family.
AB  - The Gal beta 1,3(4)GlcNAc alpha 2,3-sialyltransferase forms the NeuAc alpha
      2,3Gal beta 1,3(4)GlcNAc sequences found in terminal carbohydrate groups of
      glycoproteins and glycolipids. High energy collision-induced dissociation
      analysis of tryptic peptides from only 300 pmol of the purified Gal beta
      1,3(4)GlcNAc alpha 2,3-sialyltransferase provided 25% of the total amino acid
      sequence and led to the successful cloning of this enzyme. The peptide sequence
      information was used to design short degenerate primers for use in the polymerase
      chain reaction. A long specific cDNA fragment was amplified which was used to
      isolate a clone from a rat liver cDNA library. The cloned cDNA encodes a 374
      amino acid protein containing an amino-terminal signal-anchor sequence
      characteristic of all cloned glycosyltransferases and produced sialyltransferase
      activity when transiently expressed in COS-1 cells. When compared with two other
      cloned sialyltransferases, the primary structure of Gal beta 1,3(4)GlcNAc alpha
      2,3-sialyltransferase revealed a homologous region in all three enzymes
      consisting of a stretch of 55 amino acids located in their catalytic domains.
      This feature together with lack of homology in the remaining 85% of the sequence
      of the three sialyltransferases defines a pattern of sequence homology not found
      in cloned cDNAs of other glycosyltransferase families.

PMID- 1400417
TI  - Preferential translation of heat shock mRNAs in HeLa cells deficient in protein
      synthesis initiation factors eIF-4E and eIF-4 gamma.
AB  - Expression of antisense RNA against eukaryotic translation initiation factor 4E
      (eIF-4E) in HeLa cells causes a reduction in the levels of both eIF-4E and eIF-4
      gamma (p220) and a concomitant decrease in the rates of both cell growth and
      protein synthesis (De Benedetti, A., Joshi-Barve, S., Rinker-Schaffer, C., and
      Rhoads, R. E. (1991) Mol. Cell Biol. 11, 5435-5445). The synthesis of most
      proteins in the antisense RNA-expressing cells (AS cells) is decreased, but
      certain proteins continue to be synthesized. In the present study, we identified
      many of these as stress-inducible or heat shock proteins (HSPs). By mobilities on
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by reactivity with
      monoclonal antibodies generated against human HSPs, four of these were shown to
      be HSP 90, HSP 70, HSP 65, and HSP 27. The steady-state levels of HSP 90, 70, and
      27 were elevated in relation to total protein in AS cells. Pulse labeling and
      immunoprecipitation indicated that HSP 90 and HSP 70 were synthesized more
      rapidly in AS cells than in control cells. The accelerated synthesis of HSPs in
      the AS cells was not due, however, to increased mRNA levels; the levels of HSP 90
      and 70 mRNAs either remained the same or decreased after induction of antisense
      RNA expression. Actin mRNA, a typical cellular mRNA, was found on high polysomes
      in control cells but shifted to smaller polysomes in AS cells, as expected from
      the general decrease in translational initiation caused by eIF-4E and eIF-4 gamma
      depletion. HSP 90 and 70 mRNAs showed the opposite behavior; they were associated
      with small polysomes in control cells but shifted to higher polysomes in AS
      cells. These results demonstrate that HSP mRNAs have little or no requirement in
      vivo for the cap-recognition machinery and suggest that these mRNAs may utilize
      an alternative, cap-independent mechanism of translational initiation.

PMID- 1400418
TI  - Endo-xyloglucan transferase, a novel class of glycosyltransferase that catalyzes
      transfer of a segment of xyloglucan molecule to another xyloglucan molecule.
AB  - Xyloglucans are the major component of plant cell walls and bind tightly to the
      surface of individual cellulose microfibrils, thereby cross-linking them into a
      complex polysaccharide network of the cell wall. The cleavage and reconnection of
      xyloglucan cross-links are considered to play the leading role during chemical
      processes essential for wall expansion and, therefore, cell growth and
      differentiation. Although it is hypothesized that some transglycosylation is
      involved in these chemical processes, the enzyme responsible for the reaction was
      not identified. We have now purified a novel class of endo-type
      glycosyltransferase to apparent homogeneity from the extracellular space or the
      cell wall of the epicotyls of Vigna angularis, a bean plant. The enzyme is a
      glycoprotein with a molecular mass of about 33 kDa. The enzyme catalyzes both 1)
      endo-type splitting of a xyloglucan molecule and 2) linking of a newly generated
      reducing end of the xyloglucan to the nonreducing end of another xyloglucan
      molecule, thereby mediating the transfer of a large segment of the xyloglucan to
      another xyloglucan molecule. The transferase exhibits no glycosidase or glycanase
      activity. Substrate specificity of the enzyme was investigated using several
      polysaccharides with different glycosidic linkages as donor substrates and
      pyridylamino oligosaccharides as acceptor substrates, in which the reducing end
      of the carbohydrate was tagged with a fluorescent group. The enzyme required a
      basic xyloglucan structure, i.e. a beta-(1-->4)-glucosyl backbone with xylosyl
      side chains, for both acceptor and donor activity. Galactosyl or fucosyl side
      chains on the main chain were not required for the acceptor activity. The enzyme
      exhibited higher reaction rates when xyloglucans with higher M(r) were used as
      donor substrates. Xyloglucans smaller than 10 kDa were no longer the donor
      substrate. On the other hand, pyridylamino heptasaccharide acted as a good
      acceptor as did xyloglucan polymers. Based on these results we propose to
      designate this novel enzyme a xyloglucan: xyloglucano-transferase, to be
      abbreviated endo-xyloglucan transferase (EXT) or xyloglucan recombinase. This
      enzyme is the first enzyme identified that mediates the transfer of a high M(r)
      segment between polysaccharide molecules to generate chimeric polymers. We
      conclude that endo-xyloglucan transferase functions as a reconnecting enzyme for
      xyloglucans and is involved in the interweaving or reconstruction of cell wall
      matrix, which is responsible for chemical creepage that leads to morphological
      changes in the cell wall.

PMID- 1400419
TI  - Molecular heterogeneity of the gamma-aminobutyric acid (GABA) transport system.
      Cloning of two novel high affinity GABA transporters from rat brain.
AB  - cDNA clones encoding two novel gamma-aminobutyric acid (GABA) transporters
      (designated GAT-2 and GAT-3) have been isolated from rat brain, and their
      functional properties have been examined in mammalian cells. The transporters
      display high affinity for GABA (Km approximately 10 microM) and exhibit
      pharmacological properties distinct from the previously cloned neuronal GABA
      transporter (GAT-1). Both transporters require sodium and chloride for transport
      activity. The nucleotide sequences of GAT-2 and GAT-3 predict proteins of 602 and
      627 amino acids, respectively, which can be modeled with 12 transmembrane
      domains, similar to the topology proposed for other cloned neurotransmitter
      transporters. Localization studies indicate that both transporters are present in
      brain and retina, while GAT-2 is also present in peripheral tissues. The cloning
      of these transporter genes from rat brain reveals previously undescribed
      heterogeneity in GABA transporters.

PMID- 1400420
TI  - Identification of N-acetylneuraminyl alpha 2-->3 poly-N-acetyllactosamine glycans
      as the receptors of sialic acid-binding Streptococcus suis strains.
AB  - Streptococcus suis is a common cause of sepsis, meningitis, and other serious
      infections in young piglets and also causes meningitis in humans. The cell
      binding specificity of sialic acid-recognizing strains of Streptococcus suis was
      investigated. Treatment of human erythrocytes with sialidase or mild periodate
      abolished hemagglutination. Hemagglutination inhibition experiments with sialyl
      oligosaccharides indicated that the adhesin preferred the sequence NeuNAc alpha 2
      3Gal beta 1-4Glc(NAc). Resialylation of desialylated erythrocytes with Gal beta 1
      3(4)GlcNAc alpha 2-3-sialyltransferase induced a strong hemagglutination, whereas
      no or only weak hemagglutination was obtained with cells resialylated with two
      other sialyltransferases. Binding of radiolabeled bacteria to blots of
      erythrocyte membrane proteins revealed binding to the poly-N-acetyllactosamine
      containing components Band 3, Band 4.5, and polyglycosyl ceramides and to
      glycophorin A. The involvement of glycophorin A as a major ligand was excluded by
      the strong hemagglutination of trypsin-treated erythrocytes and En(a-)
      erythrocytes defective in glycophorin A. Sensitivity of the hemagglutination
      toward endo-beta-galactosidase treatment of erythrocytes and inhibition by
      purified poly-N-acetyllactosaminyl glycopeptides indicated that the adhesin bound
      to glycans containing the following structure: NeuNAc alpha 2-3Gal beta 1-4GlcNAc
      beta 1-3Gal beta 1-.

PMID- 1400421
TI  - Mapping single cysteine mutants of light chain 2 in chicken skeletal myosin.
AB  - The NH2- and COOH-terminal regions of the regulatory light chain (LC2) have been
      mapped to the head/rod junction by immunoelectron microscopy, using monoclonal
      and anti-fluorescyl antibodies as probes. In order to map the entire length of
      the light chain, we have engineered and purified mutants that contain a single
      cysteine residue at positions 2, 73, 94, 126, or 155. The single cysteine
      residues were labeled with either 5-iodoacetamido fluorescein or N-ethylmaleimide
      biotin. We observed that the reactivity of Cys126 is far greater than that of
      Cys155, confirming that cysteine 126 is the fast-reacting thiol in wild-type
      light chain. The labeled light chains were exchanged into myosin stripped of its
      native LC2 by immunoaffinity chromatography, and the reconstituted myosin was
      reacted with anti-fluorescein antibody or avidin prior to rotary shadowing for
      electron microscopy. The position of the antibody or avidin was found to be near
      the head/rod junction for all mutants. These mapping studies, together with our
      finding that cysteines widely separated in the primary sequence can form multiple
      disulfide bonds (Saraswat, L.D., and Lowey, S. (1991) J. Biol. Chem. 226, 19777
      19785), support a model for LC2 as a flexible, globular molecule localized mainly
      in the vicinity of the head/rod junction of myosin.

PMID- 1400422
TI  - Expression and analysis of recombinant Amb a V and Amb t V allergens. Comparison
      with native proteins by immunological assays and NMR spectroscopy.
AB  - The Amb V allergens are small, highly disulfide-bonded ragweed pollen allergens
      that serve as useful models for understanding the molecular basis of the human
      immune response. We have produced recombinant Amb a V and Amb t V (from short and
      giant ragweed pollens, respectively) in Escherichia coli and have compared their
      structural and functional characteristics to those of the native proteins.
      Recombinant Amb t V was indistinguishable from native Amb t V as determined by
      NMR spectroscopy and antibody-binding studies. Whereas inhibition analysis showed
      that recombinant Amb a V possessed only approximately 50% of the antibody-binding
      activity of native Amb a V, the two proteins were similarly effective in
      stimulating Amb a V-specific T-cells. Our results demonstrate that even highly
      homologous proteins exhibit different abilities to fold into their native three
      dimensional conformations and establish the potential and limits of expressing
      the recombinant Amb V allergens intracellularly in E. coli.

PMID- 1400423
TI  - Conveyance of partial agonism/antagonism to bombesin/gastrin-releasing peptide
      analogues on Swiss 3T3 cells by a carboxyl-terminal leucine insertion.
AB  - Gastrin-releasing peptide (GRP) is a neuroendocrine hormone that may be involved
      in the pathophysiology of small cell lung carcinoma. We describe carboxylterminal
      peptide analogues of GRP and bombesin, a 14-residue amphibian homologue, that
      were modeled after the antagonist [Leu13-psi(CH2NH)-Leu14]bombesin and retained
      the psi bond. Three novel peptides contained a Leu insertion amino to the psi
      bond, i.e. ... Leu13Leu14 psi X (residues numbered after bombesin) where X =
      LeuNH2 or norleucine-NH2). The Leu-insertion analogues behaved as pure partial
      agonists/antagonists when examined for the ability to stimulate [3H]thymidine
      incorporation into quiescent Swiss 3T3 cells (agonist activity) and to diminish
      the agonist response of GRP (antagonist activity). A time course of [3H]thymidine
      incorporation into quiescent cells indicated maximal incorporation at 20-h post
      peptide addition for bombesin and GRP and a Leu-insertion peptide, but the extent
      of the incorporation for the Leu-insertion peptide was half that of GRP and
      bombesin. The agonist dose responses of the Leu-insertion peptides (EC50 values
      of 1-10 nM) paralleled GRP and bombesin, but the maximal response of the Leu
      insertion peptides, even at concentrations as high as 10(-4) M, was half the
      maximal value of GRP or bombesin. High concentrations of the Leu-insertion
      peptides antagonized 10 nM GRP (a concentration that produced a near-maximal GRP
      response) yielding a response that was half the maximal value of GRP and
      equivalent to the maximal response of the Leu-insertion peptides alone. Analogues
      of the form ... Leu13 psi X behaved as complete antagonists. The KD values of the
      Leu-insertion peptides for competitive binding versus 125I-GRP (2-50 nM) were as
      potent as parent ... Leu14 agonists. Stability studies indicated that peptide
      potencies for both agonist and antagonist activities diminished upon peptide
      incubation in medium or on cells. The results suggested that, for the Leu
      insertion peptides, degradation into distinct products with different activities
      was not responsible for their partial agonist/antagonist behavior. Computer
      generated molecular modeling studies indicated that the novel structures could
      adopt energy minimized conformations for either an agonist or an antagonist as
      proposed earlier (Coy, D.H., Heinz-Erian, P., Jiang, N.-Y., Sasaki, Y., Taylor,
      J., Moreau, J.-P., Wolfrey, W.T., Gardner, J.D., and Jensen, R. T. (1988) J.
      Biol. Chem. 263, 5056-5060).

PMID- 1400424
TI  - Specific binding sites for the activator protein, ALCR, in the alcA promoter of
      the ethanol regulon of Aspergillus nidulans.
AB  - ALCR is the specific activator of the Aspergillus nidulans ethanol-utilization
      pathway, mediating the induction of its own transcription and that of the
      structural genes alcA and aldA, encoding respectively, alcohol dehydrogenase I
      and aldehyde dehydrogenase. ALCR is a DNA binding protein in which 6 cysteines
      are coordinated in a zinc binuclear cluster. This domain was fused to glutathione
      S-transferase (GST) and isolated as a GST-ALCR(7-58*) fusion protein from
      Escherichia coli. Mobility shift assays showed that the ALCR fusion protein binds
      at sites upstream of the alcA promoter. DNaseI protection footprinting
      experiments revealed three specific binding sites, two that are direct repeats
      and one that is an inverted repeat with the same half-site 5'-CCGCA-3'. The half
      sites are separated by a variable number of nucleotides in both types of target.
      The interaction of the ALCR fusion protein with direct and inverted repeats were
      examined by using interference and protection footprinting assays. In both
      binding sites, modification of the guanines in the half-sites interfered with the
      formation of the DNA complex, but the adjacent ones did not. Our results suggest
      that the ALCR protein makes contact in the major groove of the DNA helix of the
      half-sites. The functionality of two out of three binding sites of the GST-ALCR
      protein was demonstrated after their deletion. Therefore, the region encompassing
      these binding sites is a cis-acting element involved in the full induction of the
      alcA gene.

PMID- 1400425
TI  - Transcriptional control of nuclear genes for the mitochondrial muscle ADP/ATP
      translocator and the ATP synthase beta subunit. Multiple factors interact with
      the OXBOX/REBOX promoter sequences.
AB  - The OXBOX promoter regions of the genes for the muscle-specific adenine
      nucleotide translocator (ANT1) and the beta subunit of the ATPsynthase (ATPsyn
      beta) have been implicated in the increased transcription of these nuclear
      encoded oxidative phosphorylation (OXPHOS) genes in heart and skeletal muscle.
      DNA binding, electrophoretic mobility shift (gel-shift) assays now reveal that
      the OXBOX region has two unique but overlapping elements, the 13-base pair (bp)
      OXBOX and an 8-bp REBOX. The OXBOX binding factors are found only in myogenic
      cell lines, whereas the REBOX factors are ubiquitous. Methylation interference
      experiments have defined the boundaries of the OXBOX and REBOX elements,
      confirmed that the OXBOX factors are muscle-specific, and shown that the OXBOX
      and REBOX factors do not bind concurrently. The binding of the REBOX factors was
      found to be sensitive to NADH and thyroxine, suggesting that it may modulate
      OXPHOS gene expression in response to environmental and hormonal changes. Hence,
      the OXBOX/REBOX complex provides one mechanism by which mammalian energy
      metabolism can be adapted to developmental and environmental demands.

PMID- 1400426
TI  - The 39-kDa receptor-associated protein interacts with two members of the low
      density lipoprotein receptor family, alpha 2-macroglobulin receptor and
      glycoprotein 330.
AB  - The 39-kDa receptor-associated protein (RAP) binds to the alpha 2-macroglobulin
      receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) and
      inhibits binding of ligands to this receptor. The in vivo function of RAP may be
      to regulate ligand binding and/or assist in the correct biosynthetic processing
      or trafficking of the alpha 2MR/LRP. Here we show that RAP binds another putative
      receptor, the kidney glycoprotein 330 (gp330). Gp330 is a high molecular weight
      glycoprotein that is structurally similar to both the alpha 2MR/LRP and low
      density lipoprotein receptor. The ability of RAP to bind to gp330 was
      demonstrated by ligand blotting and solid phase binding assays, which showed that
      RAP binds to gp330 with high affinity (Kd = 8 nM). Exploiting the interaction of
      gp330 and RAP, we purified gp330 by affinity chromatography with a column of RAP
      coupled to Sepharose. Gp330 preparations obtained by this procedure were notably
      more homogeneous than those obtained by conventional methods. Immunocytochemical
      staining of human kidney sections localized RAP to the brush-border epithelium of
      proximal tubules. The fact that gp330 is also primarily expressed by proximal
      tubule epithelial cells strengthens the likelihood that the interaction between
      gp330 and RAP occurs in vivo. The functional significance of RAP binding to gp330
      may be to antagonize ligand binding as has been demonstrated for the alpha
      2MR/LRP or to assist in the biosynthetic processing and/or trafficking of this
      receptor.

PMID- 1400427
TI  - Interactions of the eIF-4F subunits in the yeast Saccharomyces cerevisiae.
AB  - Recognition of the cap structure at the 5' end of mRNA is one of the first events
      in initiation of eukaryotic translation. This step is mediated by the translation
      initiation factor 4F (eIF-4F). In mammalian cells this factor is composed of the
      cap-binding protein eIF-4E, eIF-4A, and a 220-kDa polypeptide. In yeast
      Saccharomyces cerevisiae, eIF-4E is found associated with a 150-kDa protein
      (p150) and a 20-kDa protein (p20). The resulting protein complex is proposed to
      represent yeast eIF-4F. To study the functions of p150 and p20 and their
      interaction with eIF-4E, we disrupted the genes encoding p150 and p20 and
      analyzed the effects on protein complex formation and cell viability. Yeast cells
      with single and double disruptions of the genes encoding p150 and p20 are viable,
      but p150 single and p150/p20 double disruptions show a slow growth phenotype. Gel
      chromatography and immunoadsorption experiments with a monoclonal anti-eIF-4E
      antibody coupled to protein G-Sepharose show that both p150 and p20 bind
      independently of each other to eIF-4E.

PMID- 1400428
TI  - FeMo cofactor synthesis by a nifH mutant with altered MgATP reactivity.
AB  - We have characterized a Nif- mutant of Azotobacter vinelandii, designated UW91
      (Shah, V. K., Davis, L. C., Gordon, J. K., Orme-Johnson, W. H., and Brill, W. J.
      (1973) Biochim. Biophys. Acta 292, 246-255). The specific Fe protein mutation
      giving rise to the Nif- phenotype was shown by DNA sequencing and site-directed
      mutagenesis to be the substitution of a conserved alanine at position 157 by a
      serine. The UW91 Fe protein was purified and shown to have a normal [4Fe-4S]
      cluster and normal MgATP binding activity. The substitution of alanine 157 by
      serine, however, prevents the MgATP-induced conformational change that occurs for
      the wild-type Fe protein, prevents MgATP hydrolysis, and prevents productive
      electron transfer to the MoFe protein. The UW91 Fe protein does bind to the MoFe
      protein to give a normal cross-linking pattern; however, it does not compete very
      successfully with wild-type Fe protein in an activity assay. The UW91 MoFe
      protein was also purified and characterized and shown to be indistinguishable
      from the wild-type protein. Thus, the substitution of Fe protein residue alanine
      157 by serine does not change the Fe protein's ability to function in FeMo
      cofactor biosynthesis or insertion. This demonstrates that these events do not
      require the MgATP-induced conformational change, MgATP hydrolysis, or productive
      electron transfer to the MoFe protein.

PMID- 1400429
TI  - Recombinant von Willebrand factor Arg578-->Gln. A type IIB von Willebrand disease
      mutation affects binding to glycoprotein Ib but not to collagen or heparin.
AB  - von Willebrand factor (vWF) is a multimeric plasma glycoprotein that mediates
      platelet adhesion to the subendothelium via binding to platelet glycoprotein Ib
      (GPIb) and to components of the vessel wall. Recently, missense mutations that
      cause type IIB von Willebrand disease (vWD) were described, clustered within a
      disulfide loop in the A1 domain of vWF that has binding sites for GPIb, collagen,
      and heparin. In type IIB vWD, plasma vWF exhibits increased affinity for platelet
      GPIb, but decreased binding to collagen and heparin. The effect was studied of a
      type IIB vWD mutation, Arg578-->Gln, on the interaction of vWF with GPIb,
      collagen, and heparin. Recombinant wild type rvWF and mutant rvWF(R578Q) were
      expressed in COS-7 cells. Ristocetin-induced binding of rvWF(R578Q) to GPIb was
      markedly increased compared with rvWF, confirming that the Arg578-->Gln mutation
      causes the characteristic gain-of-function abnormality of type IIB vWD;
      botrocetin-induced binding was only slightly increased. Binding to collagen type
      III and heparin-agarose was compared for rvWF(R578Q) and plasma vWF from patients
      with four different type IIB mutations: Arg543-->Trp, Arg545-->Cys, Val553-->Met,
      Arg578-->Gln. For all of the plasma samples, binding to collagen and to heparin
      was reduced compared with normal plasma. In contrast, binding of rvWF(R578Q) to
      collagen and heparin was normal compared with wild type rvWF. Therefore, the
      Arg578-->Gln mutation increases the affinity of vWF for GPIb but does not
      directly impair vWF interaction with collagen or heparin. Arg578 may therefore be
      necessary to prevent normal vWF from interacting with GPIb. In type IIB vWD, the
      defective binding of plasma vWF to collagen and heparin may be secondary to post
      synthetic modifications that occur in vivo, such as the loss of high molecular
      weight vWF multimers.

PMID- 1400430
TI  - Structure, chromosomal assignment, and expression of the gene for proteinase-3.
      The Wegener's granulomatosis autoantigen.
AB  - Proteinase-3 (PR-3) is a neutral serine proteinase present in the azurophil
      granules of human polymorphonuclear leukocytes. It degrades a variety of
      extracellular matrix proteins including elastin in vitro and causes emphysema
      when administered by tracheal insufflation to hamsters. It is identical to the
      target autoantigen (c-ANCA) associated with Wegener's granulomatosis and to
      myeloblastin, a serine proteinase first identified in HL-60 leukemia cells. In
      this study, the gene encoding PR-3 was cloned and sequenced. The gene spans
      approximately 6.5 kilobase pairs and consists of five exons and four introns. The
      genomic organization of PR-3 is similar to that of the other serine proteinases
      expressed in hemopoietic cells. Each residue of the catalytic triad of PR-3 is
      located on a separate exon, and the positions of the residues within the exons
      are similar to those in human leukocyte elastase and cathepsin G. The phase and
      placement of the introns in the PR-3 gene are also similar to those in human
      leukocyte elastase and cathepsin G. The 400-base pair (bp) 5'-flanking sequence
      of the PR-3 gene contains a TATA box at position 379. There is no CAAT box
      promoter element. The 3'-untranslated region is 200 bp, extending from a TGA stop
      codon to the site of polyadenylation 10 bp after the canonical AATAAA signal.
      Amplification of PR-3 from a human/hamster hybrid cell line localizes the gene to
      human chromosome 19. Evidence from Northern analysis suggests that PR-3
      expression is primarily confined to the promyelocytic/myelocytic stage of bone
      marrow development.

PMID- 1400431
TI  - Nuclear protein binding to the 5' enhancer region of the intracisternal A
      particle long terminal repeat.
AB  - The interactions of nuclear proteins from embryonal carcinoma cells (PCC3) with
      the long terminal repeats (LTRs) of murine intracisternal A particle (IAP) genes
      were studied. Two protein-DNA complexes were detected between PCC3 nuclear
      extract and IAP LTRs in a gel mobility shift assay. An additional complex was
      observed when enriched fractions from a heparin-agarose column were used as the
      source of proteins. Two regions within the LTR of IAP 81 were identified as the
      sites of protein interaction by DNase I protection. One region encompasses 43
      nucleotides within the U3 region at the 5' end of LTR 81. The other covers a 78
      base pair region lying within 100 nucleotides upstream from the transcription
      initiation site. Studies using constructs containing intact or deleted versions
      of the LTR fused to the bacterial chloramphenicol acetyltransferase gene
      indicated that the absence of the 5' 47 base pairs reduced the level of
      chloramphenicol acetyltransferase transcription to 20% of that driven by the
      entire LTR. Southwestern analysis of PCC3 nuclear extracts and column fractions
      revealed that a 28,000- and a 46,000-dalton protein were the major species that
      interact with the 5' end of IAP LTR 81.

PMID- 1400432
TI  - Transcription of IL-2 and IL-4 genes is not inhibited by cyclosporin A in
      competent T cells.
AB  - Cyclosporin A (CsA) inhibits T-cell proliferation primarily by blocking the
      transcription of several early activation genes, especially those of the
      important T-cell growth factors IL-2 and IL-4. This effect seems to be mediated
      through inhibition of the activity of the transcription factor NF-AT which is
      essential for IL-2 and probably for IL-4 gene transcription. However, once T
      cells are rendered "competent" to proliferate following a brief exposure to the
      phorbol ester, phorbol 12,13-dibutyrate (PDBu), and the calcium ionophore,
      ionomycin, CsA no longer inhibits cell cycle progression supported by the
      presence of PDBu alone. Here it is shown that transcription of the IL-2 and IL-4
      genes occurs normally throughout this "progression" phase, even in the presence
      of CsA. However, further production of functional NF-AT, which began during the
      competence phase of the cell cycle, is inhibited. These data indicate that,
      although the primary initiation of transcription of IL-2 and IL-4 mRNA during
      induction of competence may be NF-AT-dependent and CsA-sensitive, the
      augmentation in the progression phase is both NF-AT-independent and CsA
      resistant.

PMID- 1400433
TI  - A novel form of fibroblast growth factor receptor 2. Alternative splicing of the
      third immunoglobulin-like domain confers ligand binding specificity.
AB  - The fibroblast growth factor receptor 2 (FGFR2) gene is expressed as
      alternatively spliced mRNAs that encode bacterially expressed kinase, the
      keratinocyte growth factor receptor, or K-sam. We have now isolated a novel FGFR2
      cDNA that is identical with the previously cloned human bacterially expressed
      kinase, except in the third immunoglobulin-like domain. The ligand binding
      properties of FGFR2 were studied by expressing the protein in rat L6 muscle
      myoblasts. Unlike human bacterially expressed kinase which binds acidic and basic
      FGF with similar affinities, FGFR2 bound acidic FGF with approximately 1000-fold
      higher affinity than basic FGF. These results indicate that alternative splicing
      of the FGFR2 gene in the region encoding the carboxyl-terminal half of the third
      immunoglobulin domain determines the ligand specificity of this group of
      receptors.

PMID- 1400434
TI  - Pulmonary surfactant protein D specifically binds to phosphatidylinositol.
AB  - Alveolar type II cells produce and secrete a complex mixture of lipids and
      proteins called pulmonary surfactant of which phospholipids are the major
      components. Surfactant proteins (SP) A, B, and C interact with phospholipids and
      are believed to play important roles in alveolar spaces. However, whether
      surfactant protein D (SP-D) interacts with phospholipids is unknown. In the
      present study, we examined whether SP-D binds to phospholipids and investigated
      phospholipid specificities of SP-D binding and the structural requirements of
      phospholipids for that binding using 125I-SP-D as a probe. 125I-SP-D bound
      exclusively to phosphatidylinositol (PI) in various phospholipids or a fraction
      containing phospholipids extracted from surfactant, which were developed on thin
      layer chromatography. 125I-SP-D also bound to PI coated on microtiter wells in a
      manner dependent upon the SP-D concentration. Unlabeled SP-D competed well with
      125I-SP-D for PI binding and the antibody against SP-D abolished 125I-SP-D
      binding to PI. PI liposome also attenuated 125I-SP-D binding to the solid phase
      PI. Ca2+ is absolutely required for the binding of SP-D to PI. SP-D failed to
      bind to lyso-PI, fatty acids derived from PI digested with phospholipase A2, or
      diacylglycerol obtained after phospholipase C treatment of PI. SP-D bound to
      neither phosphatidylinositol 4-monophosphate nor phosphatidylinositol 4,5
      diphosphate. We conclude that SP-D specifically binds to PI. This is the first
      report that demonstrates that SP-D interacts with surfactant phospholipids.

PMID- 1400435
TI  - Inhibition of glycosylphosphatidylinositol anchor formation by mannosamine.
AB  - Many eucaryotic cell surface proteins are anchored to the plasma membrane via a
      glycosylphosphatidylinositol (GPI), of which the core region is highly conserved
      from protozoa to mammalian cells. Previous studies (Lisanti, M. P., Field, M. C.,
      Caras, I. W., Menon, A. K., and Rodiguez-Boulan, E. (1991) EMBO J. 10, 1969-1977)
      showed that mannosamine blocked the expression of a recombinant GPI-anchored
      protein in Madin-Darby canine kidney cells and converted this protein to an
      unpolarized secretory product. In the present study, we examined the effect of
      mannosamine on the formation of the glycan portion of the GPI anchor precursors.
      This amino sugar inhibited the incorporation of mannose into the glycan portion,
      and the inhibition was dose-dependent. Mannosamine was shown to be incorporated
      into the glycan as mannosamine, probably mostly in the second mannose position
      and thereby to block the further addition of mannose and other anchor components.
      The products formed in the presence of this drug were characterized by gel
      filtration and high resolution TLC both before and after deamination with nitrous
      acid and dephosphorylation by HF. Galactosamine and trehalosamine were inactive
      in this system, whereas glucosamine also inhibited mannose incorporation into GPI
      intermediates.

PMID- 1400436
TI  - Transforming growth factor beta 1 stimulates the production of basic fibroblast
      growth factor binding proteoglycans in Balb/c3T3 cells.
AB  - Basic fibroblast growth factor (bFGF) binds to cell surface receptors and to
      heparin sulfate proteoglycans. Heparan sulfate binding may limit bFGF degradation
      and be an obligatory step for bFGF cell interaction. Transforming growth factor
      beta 1 (TGF-beta 1) is a potent regulator of proteoglycan production and
      composition. The possibility that TGF-beta 1 synergistically regulates bFGF
      activity by altering bFGF-proteoglycan interactions was investigated. TGF-beta 1
      increased 125I-bFGF binding to the extracellular matrix (ECM) of Balb/c3T3 cells
      2-4-fold by increasing the number of bFGF binding sites. Increased bFGF binding
      correlated with a 2-5-fold increase in the production of sulfated proteoglycans,
      including heparan sulfate proteoglycans. TGF-beta 1 selectively stimulated
      production of high molecular mass proteoglycans (190-300 kDa) in conditioned
      medium and stimulated all proteoglycans in ECM. 125I-bFGF bound to TGF-beta 1
      induced proteoglycans immobilized onto cationic nylon filters. Furthermore, ECM
      isolated from TGF-beta 1-treated cells incorporated more mitogenically active
      bFGF than native ECM. The mitogenic potential of the ECM was significantly
      reduced by treatment with heparinase. These results suggest that the ability of
      TGF-beta 1 to stimulate binding of bFGF to ECM, increase ECM heparan sulfate
      proteoglycan, and potentiate the mitogenic activity of bFGF are linked. Thus one
      aspect of TGF-beta 1/bFGF synergy may involve modulation of the ECM.

PMID- 1400437
TI  - Evolution of intestinal apolipoprotein B mRNA editing. Chicken apolipoprotein B
      mRNA is not edited, but chicken enterocytes contain in vitro editing enhancement
      factor(s).
AB  - Mammalian intestinal apolipoprotein B (apoB) messenger RNA (mRNA) undergoes
      posttranscriptional editing, changing codon 2153 from CAA in apoB100 mRNA to an
      in-frame translational stop codon (UAA) in apoB48 mRNA. By contrast, chicken
      intestinal apoB cDNA contains a CAA codon at the corresponding site and apoB mRNA
      from chicken enterocytes, kidney, and liver is unedited. The cDNA sequence of
      chicken apoB spanning the edited base is divergent from mammalian apoB cDNA
      sequence, with 70% homology over the conserved 29-nucleotide sequence (6662-6690)
      flanking codon 2153. Efficient in vitro editing of both human and rat, but not
      chicken, synthetic apoB RNA was achieved using rat enterocyte S-100 extracts. By
      contrast, chicken enterocyte S-100 extracts failed to edit chicken, rat, or human
      synthetic apoB RNA. Mixing experiments, however, revealed that chicken enterocyte
      S-100 extracts enhance the in vitro editing activity of rat, pig, and human
      enterocyte S-100 extracts upon homologous RNAs. The editing enhancement activity
      of chicken enterocyte S-100 extracts is tissue-specific, heat-sensitive,
      substrate-saturable, and sensitive to proteinase K, but resistant to micrococcal
      nuclease. The activity was partially purified by Q-Sepharose chromatography and
      has an average molecular mass of 49 kDa when analyzed by gel filtration
      chromatography. We conclude that the evolutionary adaptation of intestinal apoB
      mRNA editing requires both a requisite RNA motif and tissue-specific factors
      which mediate the site-specific modification.

PMID- 1400438
TI  - Expression of the Duchenne muscular dystrophy gene products in embryonic stem
      cells and their differentiated derivatives.
AB  - Three protein products of the Duchenne muscular dystrophy (DMD) gene were
      identified so far. These include the two very similar muscle and brain type
      dystrophins, which are encoded by 14-kilobase (kb) mRNAs, and Dp71, which is much
      smaller. Dp71 is encoded by a 6.5-kb mRNA, which is transcribed from
      approximately 6% of the giant dystrophin gene. The present investigation shows
      that Dp71 is the first product of the DMD gene detectable during development. It
      is already expressed in the pluripotent embryonic stem cells. The two 14-kb mRNAs
      encoding the dystrophins are detectable only after differentiation of specialized
      cell types. The possible implication of these findings with regard to the
      ontogenetic activation and the evolution of the DMD gene are discussed.

PMID- 1400439
TI  - Plant organelles contain distinct peptidylprolyl cis,trans-isomerases.
AB  - Peptidylprolyl cis,trans-isomerase (PPIase) activity was detected in the cytosol,
      mitochondria, and chloroplast of pea plants. Cyclosporin A inhibited the activity
      largely localized to the mitochondrial matrix while rapamycin inhibited the
      PPIase activity associated with the mitochondrial membranes. Differential
      inhibition by the two immunosuppressive drugs, the specific binding of these
      drugs to different mitochondrial fractions, and the immunological detection of a
      putative 25-kDa rapamycin-binding protein (RBP) in mitochondrial extracts attests
      to the presence in plant mitochondria of both cyclophilin and RBP classes of
      PPIases. Cyclosporin A-sensitive PPIase detected in the chloroplast was mostly
      localized to the thylakoids, which is suggestive of its function in the folding
      of membranal proteins. PPIase associated with the chloroplast stroma and the
      thylakoids was not inhibited by rapamycin nor was any cross-reactive RBP detected
      in chloroplast extracts. These results demonstrate the presence of distinct
      classes of PPIases in the mitochondria and the chloroplasts of plants.

PMID- 1400440
TI  - Staphylococcal ADP-ribosyltransferase-sensitive small G protein is involved in
      brefeldin A action.
AB  - An early event in the action of brefeldin A (BFA) is the dissociation of beta
      coat protein (beta-COP) from the Golgi membrane. We have recently shown that
      staphylococcal ADP-ribosyltransferase (epidermal cell differentiation inhibitor
      (EDIN)), which specifically modifies a small G protein, rho, mimics the action of
      BFA and disassembles the Golgi apparatus in Vero cells (Sugai, M., Chen, C-h.,
      and Wu, H. C. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 8903-8907). Three
      independent BFA-resistant cell lines (BER-40 from Vero cells, PtK1, and MDCK)
      showed cross-resistance to EDIN regarding the release of the beta-COP from the
      Golgi membrane by EDIN or BFA. BFA as well as EDIN induced disassembly of the
      actin microfilaments in Vero cells, and they both failed to induce the
      disassembly of actin microfilaments in BER-40, PtK1, and MDCK cells. BFA
      inhibited protein secretion in Vero cells but not in BFA-resistant cell lines,
      whereas EDIN did not inhibit protein secretion in either Vero or other cell
      lines. AlF-4 inhibited the effect of EDIN as well as that of BFA on the
      distribution of the beta-COP. These results suggest that an EDIN-sensitive rho
      protein together with trimeric and other small G protein(s) is involved in the
      regulation of the assembly of coated vesicles and vesicular transport in the
      Golgi apparatus.

PMID- 1400441
TI  - The endoplasmic reticulum stress protein GRP94, in addition to BiP, associates
      with unassembled immunoglobulin chains.
AB  - The molecular chaperone BiP/GRP78 associates with various polypeptides in the
      endoplasmic reticulum, including immunoglobulin chains. We now show, using
      chemical cross-linking, that another endoplasmic reticulum stress protein, GRP94,
      associates with newly synthesized immunoglobulin light and heavy chains. We
      demonstrate the presence of ternary complexes composed of immunoglobulin chains,
      BiP and GRP94. Because both BiP and GRP94 associate far less with fully assembled
      immunoglobulin than with unassembled subunits, our data suggest that GRP94, like
      BiP, functions as a molecular chaperone. The presence of both BiP and GRP94 in
      the same complex further suggests that the two stress proteins work in concert
      during the folding and assembly of immunoglobulins.

PMID- 1400442
TI  - Cloning and expression of a rat somatostatin receptor enriched in brain.
AB  - The tetradecapeptide somatostatin (SRIF) is a hormone release-inhibiting
      substance that mediates diverse effects in brain and peripheral organs via
      specific receptors. A cDNA encoding a rat SRIF receptor was identified by use of
      degenerate oligonucleotide primers and polymerase chain reaction amplification of
      cDNA prepared from transcripts expressed in rat brain. The complete cDNA encodes
      a protein of 391 amino acids with seven potential transmembrane domains.
      Expression of the cDNA product in transfected COS-7 cell lines provides the same
      high affinity of binding to [125I-Tyr11]SRIF-14 as that of rat cerebral cortex
      tissues. However, the binding of [125I-Tyr11]SRIF-14 to cloned rat SRIF receptor
      is not displaced by MK678, a SRIF analog that partially displaces [125I
      Tyr11]SRIF-14 binding sites in membranes of rat cerebral cortex. Northern
      analysis and in situ hybridization indicate that mRNA (4.0 kilobases) for cloned
      rat SRIF receptor is preferentially expressed in rat brain regions such as
      cerebral cortex and hippocampus with no detectable expression in most peripheral
      organs. This pattern contrasts with the exclusive peripheral expression of a
      recently cloned human SRIF receptor. The cDNA probe of rat receptor detects mRNA
      from mouse brain but not from human cerebral cortex and cerebellum.

PMID- 1400443
TI  - Solubilization and reconstitution of the Pseudomonas aeruginosa high affinity
      branched-chain amino acid transport system.
AB  - The high affinity branched-chain amino acid transport system (LIV-I) in
      Pseudomonas aeruginosa is composed of five components: BraC, a periplasmic
      binding protein for branched-chain amino acids; BraD and BraE, integral membrane
      proteins; BraF and BraG, putative nucleotide-binding proteins. By using a T7 RNA
      polymerase/promoter system we overproduced the BraD, BraE, BraF, and BraG
      proteins in Escherichia coli. The proteins were found to form a complex in the E.
      coli membrane and solubilized from the membrane with octyl glucoside. The LIV-I
      transport system was reconstituted into proteoliposomes from solubilized proteins
      by a detergent dilution procedure. In this reconstituted system, leucine
      transport was completely dependent on the presence of all five Bra components and
      on ATP loaded internally to the proteoliposomes. Alanine and threonine in
      addition to branched-chain amino acids were transported by the proteoliposomes,
      reflecting the substrate specificity of the BraC protein. GTP replaced ATP well
      as an energy source, and CTP and UTP also replaced ATP partially. Consumption of
      loaded ATP and concomitant production of orthophosphate were observed only when
      BraC and leucine, a substrate for LIV-I, were added together to the
      proteoliposomes, indicating that the LIV-I transport system has an ATPase
      activity coupled to translocation of branched-chain amino acids across the
      membrane.

PMID- 1400444
TI  - Purification and characterization of 7 alpha-hydroxy-4-cholesten-3-one 12 alpha
      hydroxylase.
AB  - The isoform of cytochrome P450 that catalyzes the 12 alpha-hydroxylation of 7
      alpha-hydroxy-4-cholesten-3-one, an intermediate in the conversion of cholesterol
      to cholic acid, was purified to homogeneity from rabbit liver microsomes. The
      extent of purification in the various steps was judged by an assay involving high
      performance liquid chromatography. The purified enzyme showed a single band on
      SDS-polyacrylamide gel electrophoresis (M(r) = 50,000). The NH2-terminal amino
      acid sequence is as follows: Val-Leu-Trp-Gly-Leu-Leu-Gly-Ala-Leu-Leu-Met-Val-Met
      Val-Gly-, which is different from that of any other P450s so far reported. The
      specific content of the enzyme was 13.3 nmol of cytochrome P450/mg of protein.
      Upon reconstitution with NADPH-cytochrome P450 reductase and cytochrome b5, the
      P450 enzyme showed a high activity of 12 alpha-hydroxylation with a turnover
      number of 36.6 min-1 at 37 degrees C. The omission of either cytochrome P450 or
      NADPH-cytochrome P450 reductase resulted in complete loss of activity, and the
      omission of cytochrome b5 resulted in 40% loss of activity. Antibodies prepared
      from mouse inhibited the 12 alpha-hydroxylase activity of rabbit liver microsomes
      about 90% and that of the rat liver microsomes 50%. The enzyme activity was not
      inhibited by other antibodies raised against other forms of P450 that catalyze
      different monooxygenation reactions toward xenobiotics or endogenous substrates.
      Anti-cytochrome b5 antibody inhibited the activity 40%, suggesting the functional
      role of this protein, and anti-reductase inhibited the activity almost
      completely. The microsomal enzyme activity was markedly elevated by starvation or
      streptozotocin administration to the animals. However, an immunoblotting
      experiment showed no correlation between the enzyme activity and the amount of
      protein, suggesting that post-translational modification may occur.

PMID- 1400445
TI  - Expression of human soluble tissue factor in yeast and enzymatic properties of
      its complex with factor VIIa.
AB  - The extracellular domain of human tissue factor (TF, amino acids 1-217) was
      expressed in Saccharomyces cerevisiae, using the inducible yeast acid phosphatase
      promoter and the yeast invertase signal sequence to direct its secretion into the
      culture broth. Two active soluble forms sTF alpha (high molecular weight form)
      and sTF beta (low molecular weight form) were purified, the yield being
      approximately 10 and 1 mg/liter of culture supernatant, respectively. sTF alpha
      had an apparent molecular mass of 150 kDa on SDS-polyacrylamide gel
      electrophoresis and contained more than 200 residues of mannose/mol of protein.
      sTF beta had an apparent molecular mass of 37 kDa and contained 22 residues of
      mannose/mol of protein. N-Glycosidase F treatments of both rTFs reduced the
      apparent molecular mass to 35 kDa. The amino-terminal sequences and amino acid
      compositions of sTF alpha and sTF beta were consistent with those deduced from
      the cDNA sequence, thereby indicating that the difference in molecular mass is
      caused by heterogeneity of oligosaccharide structures. Of these recombinant TFs,
      sTF beta enhanced factor VIIa-amidolytic activity 40-fold toward the chromogenic
      substrate and 147-fold toward the fluorogenic substrate, affecting mainly the
      kcat value. The enhancement was comparable with that of TF purified from human
      placenta. The TF-mediated enhancement of factor VIIa-amidolytic activity was
      inhibited by heparin-activated antithrombin III, forming a high molecular weight
      complex. As treatment of sTF beta with denaturants such as guanidine
      hydrochloride or urea led to a biphasic loss of the activity, the extracellular
      domain of TF probably consists of two discrete domains. This expression system
      provides a significant amount of the extracellular domain of TF so that studies
      of interactions with factor VII are feasible.

PMID- 1400446
TI  - Pancreatic beta cell heterogeneity in glucose-induced insulin secretion.
AB  - Rat pancreatic beta cells differ in their individual sensitivity to glucose
      inducible metabolic changes. The present study examines whether beta cells with a
      higher metabolic threshold require higher glucose levels for stimulation of their
      secretory activity. Purified beta cells were distributed according to their
      metabolic redox state at 7.5 mM glucose; the metabolically responsive (high
      responsive) and unresponsive (low responsive) subpopulations of comparable size
      and viability were reaggregated in the presence of [3H]tyrosine and then perfused
      at 2.8 mM glucose with 10-min pulses of increasing glucose concentration. Glucose
      elicited first-phase insulin release in both high and low responsive
      subpopulations from, respectively, 4.2 and 8.3 mM on. The amplitude of both
      secretory responses increased dose dependently, the rates in the high responsive
      subpopulation being 2-fold higher than in the low responsive one. At all
      stimulating glucose levels, fractional release of 3H-labeled insulin was 3- to 4
      fold higher than that of immunoreactive insulin. Preferential release of newly
      formed insulin was already maximally stimulated at 4.2 mM glucose in the high
      responsive subpopulation, whereas it increased dose-dependently in the low
      responsive one. These results indicate the existence of intercellular differences
      in the secretory activity of glucose-exposed beta cells, both in terms of glucose
      sensitivity and of amplitude. This heterogeneity in beta cell secretory
      responsiveness parallels that which has been previously described for the
      cellular metabolic and biosynthetic functions. It is concluded that glucose dose
      dependently recruits beta cells into both biosynthetic and secretory activities.
      Co-existence of inactive and activated cells can explain preferential release of
      newly synthesized over preformed hormone during glucose stimulation.

PMID- 1400447
TI  - Cross-linking of the gamma subunit of the Escherichia coli ATPase (ECF1) via
      cysteines introduced by site-directed mutagenesis.
AB  - The gamma subunit of the Escherichia coli F1 ATPase (ECF1) has been altered by
      site-directed mutagenesis to create five different mutants, gamma-S8C, gamma
      S81C, gamma-T106C, gamma-S179C, and gamma-V286C, respectively. ECF1 isolated from
      four of these mutants had ATPase activities similar to that of a wild-type
      isogenic strain used as a control, the exception was enzyme isolated from mutant
      gamma-S81C, which had an ATPase activity of around 70-80% of the wild type. ECF1
      isolated from each of the various mutants was reacted with N-(4-(7-(diethylamino)
      4-methylcoumarin-3-yl))maleimide (CM). The fluorescent reagent was incorporated
      into Cys residues placed at positions 8, 106, 179, and 286, but not at 81,
      indicating which of these Cys residues are on the surface of the gamma subunit in
      the enzyme complex. Modification of the Cys at position 106 with CM activated the
      enzyme, and modification of the Cys at position 8 inhibited ATPase activity a
      small amount; however, modification of Cys at 179 or 286 had no effect on enzyme
      activity. The four mutants with a reactive Cys were reacted with
      tetrafluorophenylazide maleimides (TFPAMs), novel photoactivatable cross-linkers.
      In the mutant gamma-S8C, cross-links were formed between the introduced Cys on
      the gamma subunit and sites on the beta subunit. This cross-linking between gamma
      and beta depended on nucleotide conditions under which the photolysis was carried
      out, with differently migrating cross-linked products being obtained in ATP +
      EDTA compared with ATP + Mg2+ or ATP + Mg2+ Pi. Cross-linking between beta and
      gamma inhibited ATPase activity in proportion to the yield of cross-linked
      product. In the mutant gamma-V286C, cross-links were formed between the
      introduced Cys on gamma and the alpha subunit which were the same in all
      nucleotide conditions and which led to inhibition of ATPase activity.

PMID- 1400448
TI  - Molecular cloning, expression, and characterization of the cDNA for the rat
      hepatic squalene synthase.
AB  - Amino acid sequence information was obtained for the NH2 terminus, and for
      endogenous peptides generated by trypsin digestion, of a purified, truncated form
      of rat hepatic squalene synthase (RSS, EC 2.5.1.21) (Shechter, I., Klinger, E.,
      Rucker, M. L., Engstrom, R. G., Spirito, J. A., Islam, M. A., Boettcher, B. R.,
      and Weinstein, D. B. (1992) J. Biol. Chem. 267, 8628-8635). Degenerate primers,
      based on the amino acid sequences, were synthesized and used for the
      amplification and sequencing of a 1708-base pair (bp) cDNA for RSS from the rat
      hepatoma cell line H35. An open reading frame of 1248 bp encoding 416 amino acids
      (M(r) = 48,103) was detected for RSS. We have constructed a pRSS1327 expression
      vector by molecular cloning of a 1327-bp cDNA, which includes sequences of the
      entire coding region for RSS, into pBluescript. Expression in Escherichia coli of
      a functional, full-length RSS was confirmed by immunoblot analysis and enzymatic
      activity. We present and evaluate a model for the secondary structure of RSS and
      its possible membrane orientation. The model predicts a 315-residue domain at the
      center of the protein that contains the catalytic site and is released in a
      soluble form by partial proteolysis. The 33-residue NH2-terminal and 98-residue
      COOH-terminal sections are not involved in catalysis. Sequence analysis of the
      catalytic domain of RSS indicate three regions with high homology to sequences in
      a number of functionally distinct proteins that utilize polyprenyl diphosphate
      substrates.

PMID- 1400449
TI  - The human MUC2 intestinal mucin has cysteine-rich subdomains located both
      upstream and downstream of its central repetitive region.
AB  - The human MUC2 mucin is a large secretory glycoconjugate that coats the epithelia
      of the intestines, airways, and other mucus membrane-containing organs. Previous
      work has shown that this mucin contains an extended tandem repeat-containing
      domain rich in Thr and Pro. In the present work we describe two additional
      regions of this mucin located both upstream and downstream of the tandem repeat
      array. The carboxyl-terminal domain contains 984 residues and can be divided into
      mucin-like (139 residues) and cysteine-rich (845 residues) subdomains. This
      latter subdomain exhibits varying degrees of sequence similarity to a wide range
      of mucins and mucin-like proteins including those isolated from rats, pigs, cows,
      and frogs. We also report here the sequence of 1270 residues lying immediately
      upstream of the tandem repeats. This region contains a repetitive, mucin-like
      subdomain and a second cysteine-rich stretch of more than 700 residues. Both
      cysteine-rich subdomains of this mucin have sequence similarity with von
      Willebrand factor, a serum protein that exists as a disulfide-linked polymer.
      This suggests that these cysteine-rich subdomains are important in the catenation
      of mucin monomers into oligomers, the structures that confer viscoelasticity upon
      mucus.

PMID- 1400450
TI  - Intermediate steps in cellular iron uptake from transferrin. Detection of a
      cytoplasmic pool of iron, free of transferrin.
AB  - The uptake of transferrin-bound iron by receptor-mediated endocytosis has been
      the subject of extensive experimental investigation. However, the path followed
      by iron (Fe) after release from transferrin (Tf) remains obscure. Once Fe is
      released from Tf within the endosome, it must be transported across the endosomal
      membrane into the cell. The present investigation describes the presence of a
      cytoplasmic Tf-free Fe pool which is detectable only when cells are detached from
      their culture dishes at low temperature, after initial incorporation of diferric
      transferrin at 37 degrees C. This cellular iron pool was greatly reduced if
      incubation temperatures were maintained at 37 degrees C or if cells were treated
      with pronase. Human melanoma cells (SK-MEL-28) in culture were prelabeled by
      incubation with human 125I-59Fe-transferrin for 2 h, washed, and reincubated at 4
      degrees C or 37 degrees C in balanced salt solution in the presence or absence of
      pronase. The cells were then mechanically detached from the plates and separated
      into "internalized" and supernatant fractions by centrifugation. Approximately
      90% of cellular 59Fe and 20% of 125I-Tf remained internalized when this
      reincubation procedure was carried out in balanced salt solution at 37 degrees C.
      However, at 4 degrees C, cellular internalized iron was reduced to approximately
      50% of the initial value. The release of this component of cellular 59Fe
      (approximately 40% of total cell 59Fe) at 4 degrees C was completely inhibited in
      the presence of pronase and other general proteinases at 4 degrees C and at 37
      degrees C, without affecting internalized transferrin levels. Similar results
      were obtained in fibroblasts and hepatoma cells, indicating that this phenomenon
      is not unique to melanoma cells. The characterization of this Tf-free cellular Fe
      pool which is detectable at low temperature may yield valuable insights into the
      metabolic fate of iron following its transport across the membrane of the
      endocytotic vesicle.

PMID- 1400451
TI  - An essential and specific subunit of RNA polymerase III (C) is encoded by gene
      RPC34 in Saccharomyces cerevisiae.
AB  - The RPC34 gene of Saccharomyces cerevisiae was cloned by immunological screening,
      using antibodies raised against the C34 polypeptide of the RNA polymerase III
      (C). This single copy gene was located near the centromere of chromosome XIV. It
      included a coding sequence of 317 amino acids that strictly matched two internal
      oligopeptides of C34. This polypeptide is a specific component of RNA polymerase
      III, with no significant homology to any other RNA polymerase subunit known so
      far. It is an essential subunit, since inactivation by deletion or nonsense
      mutations led to a recessive lethal phenotype. Moreover, a partially blocked
      mutant, rpc34-F297, had a reduced tRNA synthesis in vivo but no detectable effect
      on 5 S RNA synthesis. The latter phenotype was observed for all conditionally
      defective RNA polymerase III mutants isolated so far.

PMID- 1400452
TI  - Domain-dependent protein folding is indicated by the intracellular kinetics of
      disulfide bond formation of human chorionic gonadotropin beta subunit.
AB  - We have measured the intracellular rates of formation of the six disulfide bonds
      in the human chorionic gonadotropin beta subunit (hCG-beta) to determine whether
      the folding pathway of this molecule can be described by a simple sequential
      model. If such a model is correct, the formation of disulfide bonds, which is
      indicative of tertiary structural changes during protein folding, should occur in
      a discrete order. The individual rates of disulfide bridging were determined by
      identifying the extent of disulfide bond formation in hCG-beta intermediates
      purified from choriocarcinoma cells that had been metabolically labeled for 40 to
      120 s and chased for 0 to 25 min. The results of these kinetic studies describe a
      folding pathway in which the disulfide bonds between cysteines 34-88, 38-57, 9-90
      and 23-72 stabilize, in a discrete order, the putative domain(s) involving amino
      acids 1-90 of hCG-beta. However, the S-S bonds 93-100 and 26-110 begin to form
      before the complete formation of the disulfide bonds that stabilize the amino
      acid 1-90 domain(s), and continue to form after complete formation of these
      disulfide bonds, suggesting that hCG-beta does not fold by a simple sequential
      pathway. The order of completion of each of the six disulfide bonds of hCG-beta
      is: 34-88 (t1/2 = 1-2 min), 38-57 (t1/2 = 2-3 min), 9-90 and 23-72, 93-100, and
      26-110. Moreover, 60-100% of each of the six disulfide bonds form
      posttranslationally, and nonnative disulfide bonds do not form in detectable
      amounts during intracellular folding of hCG-beta.

PMID- 1400453
TI  - Quantitative analysis of transcription and RNA levels of 15 barley chloroplast
      genes. Transcription rates and mRNA levels vary over 300-fold; predicted mRNA
      stabilities vary 30-fold.
AB  - Higher plant plastid genomes encode rRNAs, tRNAs, and protein subunits of the RNA
      polymerase, ribosomes, and the photosynthetic apparatus which vary over 1000-fold
      in abundance. Quantitative analysis of transcription and RNA levels was carried
      out on 15 plastid genes which are located in 14 different transcription units
      covering 50% of the barley plastid genome. Transcription of 16S rRNA, trnfM-trnG,
      and trnK was high relative to most other plastid genes. Transcription of trnfM
      trnG was 5 times greater than trnK indicating that differences in tRNA levels in
      plastids could be due, in part, to differences in transcription. Among the
      protein coding genes, mRNA levels varied over 900-fold and transcription over 300
      fold. The gene showing the lowest transcription rate and mRNA level, rpoB, is
      located in a gene cluster which encodes subunits of the plastid RNA polymerase
      (rpoB-rpoC1-rpoC2). RpoA, which encodes the alpha subunit of the RNA polymerase,
      was located in a gene cluster encoding ribosomal proteins (rpl23, rps19, rpl16)
      and infA. RNA from this gene cluster is 30-fold more abundant than rpoB mRNA,
      suggesting that expression of rpoA is regulated at the level of translation or
      protein stability. Polycistronic operons encoding subunits of the photosynthetic
      apparatus (psbB-psbH-petB-petD; psbK-psbI-psbD-psbC; atpB-atpE; psaA-psaB) had
      higher transcription rates and correspondingly higher mRNA levels than genes
      which encode ribosomal proteins or RNA polymerase subunits. RbcL and psbA, which
      are located in separate transcription units, exhibited the highest transcription
      rates and mRNA levels. Correspondence between transcription rate, mRNA level, and
      protein abundance indicates that transcription is a primary determinant of barley
      plastid gene expression. In addition, a 30-fold variation in predicted mRNA
      stability was observed which further increases the dynamic range of plastid mRNA
      abundance.

PMID- 1400455
TI  - G protein-bound conformation of mastoparan-X, a receptor-mimetic peptide.
AB  - Mastoparans are a family of 14-residue peptide toxins from wasp venom which have
      been proposed to stimulate secretion from a variety of cells, by directly
      activating GTP-binding regulatory proteins (G proteins). In vitro studies have
      shown that mastoparans activate G proteins by a mechanism remarkably similar to
      that used by agonist-bound receptors (Higashijima, T., Uzu, S., Nakajima, T., and
      Ross, E. M. (1988) J. Biol. Chem. 263, 6491-6494). Here, we report the
      conformation of mastoparan-X (INWKGIAAMAKKLL-NH2) when it is bound to the alpha
      subunits of recombinant G(i) and G(o), derived from an analysis of transferred
      nuclear Overhauser effects in a two-dimensional 1H NMR spectrum of mastoparan-X
      obtained in the presence of these G proteins. Restrained molecular dynamic
      simulations with NMR-derived distance constraints were used to determine
      conformations consistent with NMR data. The G(i)- and G(o)-bound conformations of
      mastoparan-X are very similar, and in both cases, a major part of the molecule
      adopts an amphiphilic alpha-helical conformation. The lysine residues are known
      to be crucial for activity, and it is thus likely that at least the polar face of
      the amphiphilic helix is in contact with the G proteins. These conclusions should
      be useful in the design of potent and selective analogs of mastoparan and in the
      development of models for receptor-G protein interaction.

PMID- 1400454
TI  - Transgenic mice expressing full-length human apolipoprotein B-100. Full-length
      human apolipoprotein B mRNA is essentially not edited in mouse intestine or
      liver.
AB  - Apolipoprotein (apo) B-100 mRNA is edited in the small intestine (in all mammals
      examined) and the liver (in mice and rats only) to produce apoB-48 mRNA. ApoB
      mRNA editing involves a C-->U conversion of the first base of the codon CAA for
      Gln-2153 in apoB-100, changing it to an in-frame stop codon (UAA). The edited
      mRNA encodes apoB-48, which is colinear with the N-terminal 48% of apoB-100. ApoB
      mRNA editing can be reproduced in vitro using cellular extracts from one species
      to edit synthetic apoB mRNA sequences from a different species. Editing of
      transcripts from transfected genes also appears not to be species-specific. We
      have produced transgenic mice that express full-length human apoB-100 mRNA at
      high levels in the liver and small intestine. Human apoB-100 (a 550-kDa protein)
      but not apoB-48 (a 260-kDa protein) is detected in total plasma (at approximately
      22 mg/dl) and in very low density and low density lipoproteins. The endogenous
      mouse plasma apoB concentration is reduced by approximately 45% in the transgenic
      animals. Thus, the transgenic mice form an animal model for familial
      hyperapolipoprotein B, an inherited form of hyperlipidemia. To our surprise, we
      found that the full-length human apoB mRNA consists of > 99% apoB-100 mRNA in
      both the liver and small intestine; < 1% of edited (apoB-48) mRNA was detected.
      The proportions of endogenous mouse apoB-48 (edited) mRNA (60 and 90% in the
      liver and small intestine, respectively) were identical in transgenic mice and
      their nontransgenic littermates. Therefore, full-length human apoB mRNA is
      resistant to editing by the mouse editing enzyme in vivo; the unchanged
      proportion of endogenous mouse apoB-48 mRNA in the transgenic mice suggests that
      the human mRNA competes poorly with the mouse sequence for interacting with the
      editing enzyme. This observation has implications for the sequence specificity
      and mechanism of RNA editing. Furthermore, we should exercise caution in the
      interpretation of in vitro RNA-editing experiments.

PMID- 1400456
TI  - Calcium and magnesium dependence of phospholipase A2-catalyzed hydrolysis of
      phosphatidylcholine small unilamellar vesicles.
AB  - The Ca2+ requirement for lipid hydrolysis catalyzed by phospholipase A2 from
      Agkistrodon piscivorus piscivorus (App-D49) and porcine pancreas has been
      examined using small, unilamellar vesicles of dipalmitoylphosphatidylcholine
      (DPPC SUV). Hydrolysis was affected by product inhibition even at early times,
      and the extent of this inhibition depended on the concentration of divalent
      cations. The Ca2+ requirement for half-maximal rates of hydrolysis reflected, in
      part, this non-catalytic role of divalent cations. The presence of 10 mM Mg2+, a
      cation which does not support catalysis, reduced the Ca2+ required for half
      maximal rates of hydrolysis from millimolar concentrations to 40 microM for App
      D49. Since the dissociation constant of the enzyme for Ca2+ in solution is 2 mM,
      these results indicate a change in the interaction of the enzyme with Ca2+ under
      catalytic conditions. The kinetic dissociation constant of Ca2+ for the
      pancreatic enzyme was 20 microM which is substantially lower than the
      dissociation constant in solution, 0.35 mM. The similarity of apparent kinetic
      dissociation constants for these enzymes suggests that structurally similar
      features determine the affinity for Ca2+ under catalytic conditions. Evidence is
      presented that the affinity of phospholipase A2 for Ca2+ changes subsequent to
      the initial interaction of the enzyme with the substrate interface. However, the
      apparent Michaelis constant, KMapp, for App-D49, 0.03-0.06 mM, is independent of
      [Ca2+] and is about the same as the equilibrium dissociation constant for DPPC
      SUV, 0.14 mM. We thus suggest that KMapp is a steady-state constant.

PMID- 1400457
TI  - Identification of a pharmacologically distinct prostaglandin H synthase in
      cultured epithelial cells.
AB  - Nonsteroidal anti-inflammatory drugs inhibit the action of prostaglandin H
      synthase (PGH synthase), and this effect may constitute the basis for therapeutic
      and idiosyncratic responses to these agents. We found that aspirin treatment of
      cultured ovine tracheal epithelial cells blocked PGH synthase-catalyzed formation
      of PG as expected but also caused a dose-dependent increase in 15
      hydroxyeicosatetraenoic acid (15-HETE) production from arachidonic acid. In
      contrast, aspirin caused only inhibition of PG production without enhancing 15
      HETE formation in ovine seminal vesicle and other tissues. The 15-HETE formed by
      aspirin-treated ovine tracheal epithelial cells was generated by a PGH synthase
      dependent mechanism because: (i) the 15-HETE forming activity was just as
      sensitive as PG forming activity to selective inhibition by indomethacin; (ii)
      both 15-HETE and PG forming activities were quantitatively immunoprecipitated
      (depleted from supernatants and recovered in immune complex pellets) by a
      specific anti-PGH synthase antiserum. Additional immunoprecipitation experiments
      indicated that anti-PGH synthase monoclonal antibodies (cyo-1 and cyo-5) raised
      against the aspirin-inhibited form of the enzyme (contained in seminal vesicle)
      did not recognize the aspirin-stimulated 15-HETE-forming PGH synthase (contained
      in cultured epithelial cells). Thus, sequential immunoprecipitation of cultured
      epithelial cell material first with excess cyo-1 followed by anti-PGH synthase
      antiserum indicated that two isoforms of PGH synthase were expressed in these
      cells. SDS-polyacrylamide gel electrophoresis of immunoprecipitated PGH synthase
      from cultured epithelial cells revealed distinct protein bands for each form of
      the enzyme (M(r) = 70,000 and 72,000). The identification of a distinct PGH
      synthase which may be modified by aspirin so that selective oxygenation of fatty
      acid substrate is enhanced (while PG formation is inhibited) indicates that
      isozymes of PGH synthase exist which are pharmacologically distinct.

PMID- 1400458
TI  - Human DNA polymerases alpha and beta are able to incorporate anti-HIV
      deoxynucleotides into DNA.
AB  - Deoxynucleoside analogs, AZT and/or ddN, are the therapeutic agents currently
      utilized to inhibit the human immunodeficiency virus (HIV) reverse transcriptase.
      The effects of their anabolic products, AZT-triphosphate (AZT-TP) and ddCTP on
      human cellular DNA metabolic processes were studied using highly purified,
      structurally and enzymatically defined forms of the two major human host DNA
      polymerases, alpha and beta, and compared to those of the reverse transcriptase
      purified from HIV viron. Human DNA polymerase alpha during processive DNA
      synthesis is able to incorporate AZT-monophosphate (AZT-MP) but not ddCMP into
      DNA, causing chain termination. During its initial encounter with a primer
      terminus, polymerase alpha is able to incorporate both AZT-MP and ddCMP into DNA
      chains. Polymerase beta is able to incorporate AZT-MP and ddCMP into DNA, causing
      chain termination in both modes of DNA synthesis. Steady state kinetic analyses
      demonstrate that polymerase alpha inserts one AZT-MP molecule into DNA for every
      2500 dTMP molecules incorporated. Polymerase beta incorporates ddCMP with
      efficiency nearly equal to that of dCMP. HIV reverse transcriptase prefers to
      incorporate AZT-MP and ddCMP rather than dTMP and dCMP, respectively. The
      findings described here raise the concern that the capability of the two major
      host DNA polymerases to incorporate AZT-MP or ddCMP into DNA might cause adverse
      side effects on human DNA metabolism and mutation in the genomes of patients
      under long term continuous treatment with AZT and ddC.

PMID- 1400459
TI  - Flow cytometric kinetic measurements of neutrophil phospholipase A activation.
AB  - The interrelationships between activation of phospholipases and neutrophil
      stimulus-induced Ca2+ responses remain unclear. We report here that immune
      complexes activate a phosphatidylcholine-specific phospholipase A in a neutrophil
      only after the cytoplasmic Ca2+ transient has been initiated in the same cell,
      while chemotactic peptide activation does not proceed via such a phospholipase A
      mediated mechanism. Measurements of [Ca2+] changes and of phosphatidylcholine
      specific phospholipase A activity were made by flow cytometry, using Indo-1 for
      Ca2+ indication, and a new fluorescent probe, bis-BODIPY-phosphatidylcholine,
      localized in the inner leaflet of the plasma membrane, to measure phospholipase A
      activation. Both 100 nM formyl-methionyl-leucyl-phenylalanine (with or without
      cytochalasin B) and 60 micrograms/ml insoluble immune complexes elicited
      cytoplasmic Ca2+ transients, but only insoluble immune complexes stimulated
      phospholipase A activation in a subpopulation of cells exhibiting an elevation of
      [Ca2+]in. Phospholipase A activation followed the Ca2+ transient, starting, in
      each cell, after [Ca2+]in had begun to decrease as Ca2+ redistributed in the
      activated cell. The products of this phospholipase activation were confirmed by
      thin layer chromatography. We conclude that neutrophils respond to immune
      complexes with an elevated cytoplasmic Ca(2+)-requiring phosphatidylcholine
      specific phospholipase A activation and to chemotactic peptides by a different
      mechanism.

PMID- 1400460
TI  - Further examination of seventeen mutations in Escherichia coli F1-ATPase beta
      subunit.
AB  - Seventeen mutations in beta-subunit of Escherichia coli F1-ATPase which had
      previously been characterized in strain AN1272 (Mu-induced mutant) were expressed
      in strain JP17 (beta-subunit gene deletion). Six showed unchanged behavior,
      namely: C137Y; G142D; G146S; G207D; Y297F; and Y354F. Five failed to assemble
      F1F0 correctly, namely: G149I; G154I; G149I,G154I; G223D; and P403S,G415D. Six
      assembled F1F0 correctly, but with membrane ATPase lower than in AN1272, namely:
      K155Q; K155E; E181Q; E192Q; D242N; and D242V. AN1272 was shown to unexpectedly
      produce a small amount of wild-type beta-subunit; F1-ATPase activities reported
      previously in AN1272 were referable to hybrid enzymes containing both mutant and
      wild-type beta-subunits. Purified F1 was obtained from K155Q; K155E; E181Q;
      E192Q; and D242N mutants in JP17. Vmax ATPase values were lower, and unisite
      catalysis rate and equilibrium constants were perturbed to greater extent, than
      in AN1272. However, general patterns of perturbation revealed by difference
      energy diagrams were similar to those seen previously, and the new data
      correlated well in linear free energy relationships for reaction steps of unisite
      catalysis. Correlation between multisite and unisite ATPase activity was seen in
      the new enzymes. Overall, the data give strong support to previously proposed
      mechanisms of unisite catalysis, steady-state catalysis, and energy coupling in
      F1-ATPases (Al-Shawi, M. K., Parsonage, D. and Senior, A. E. (1990) J. Biol.
      Chem. 265, 4402-4410). The K155Q, K155E, D242N, and E181Q mutations caused 5000
      fold, 4000-fold, 1800-fold, and 700-fold decrease, respectively, in Vmax ATPase,
      implying possibly direct roles for these residues in catalysis. Experiments with
      the D242N mutant suggested a role for residue beta D242 in catalytic site Mg2+
      binding.

PMID- 1400461
TI  - Chimeras of hepatic lipase and lipoprotein lipase. Domain localization of enzyme
      specific properties.
AB  - Chimeric molecules between human lipoprotein lipase (LPL) and rat hepatic lipase
      (HL) were used to identify structural elements responsible for functional
      differences. Based on the close sequence homology with pancreatic lipase, both
      LPL and HL are believed to have a two-domain structure composed of an amino
      terminal (NH2-terminal) domain containing the catalytic Ser-His-Asp triad and a
      smaller carboxyl-terminal (COOH-terminal) domain. Experiments with chimeric
      lipases containing the HL NH2-terminal domain and the LPL COOH-terminal domain
      (HL/LPL) or the reverse chimera (LPL/HL) showed that the NH2-terminal domain is
      responsible for the catalytic efficiency (Vmax/Km) of these enzymes. Furthermore,
      it was demonstrated that the stimulation of LPL activity by apolipoprotein C-II
      and the inhibition of activity by 1 M NaCl originate in structural features
      within the NH2-terminal domain. HL and LPL bind to vascular endothelium,
      presumably by interaction with cell surface heparan sulfate proteoglycans.
      However, the two enzymes differ significantly in their heparin affinity.
      Experiments with the chimeric lipases indicated that heparin binding avidity was
      primarily associated with the COOH-terminal domain. Specifically, both HL and the
      LPL/HL chimera were eluted from immobilized heparin by 0.75 M NaCl, whereas 1.1 M
      NaCl was required to elute LPL and the HL/LPL chimera. Finally, HL is more active
      than LPL in the hydrolysis of phospholipid substrates. However, the ratio of
      phospholipase to neutral lipase activity in both chimeric lipases was enhanced by
      the presence of the heterologous COOH-terminal domain, demonstrating that this
      domain strongly influences substrate specificity. The NH2-terminal domain thus
      controls the kinetic parameters of these lipases, whereas the COOH-terminal
      domain modulates substrate specificity and heparin binding.

PMID- 1400462
TI  - Chromatin changes accompany the developmental activation of insulin-like growth
      factor I gene transcription.
AB  - Insulin-like growth factor I (IGF-I) is a potent regulator of postnatal growth in
      mammals, yet little is known about the developmental control of IGF-I synthesis.
      We have investigated the regulation of IGF-I expression in the rat in order to
      gain insight into the mechanisms of growth factor induction during early
      postnatal life. Steady-state levels of liver IGF-I mRNA increased by more than 15
      fold during the period from fetal day 18 to postnatal day 7 and reached 50% of
      adult values by day 14. Transcription run-on experiments using isolated hepatic
      nuclei and direct analysis of nuclear RNA each demonstrated a comparable rise in
      nascent IGF-I mRNA over the same time period. Over 90% of transcripts were
      directed by promoter 1, the more 5' of the two IGF-I gene promoters. By contrast
      IGF-II gene transcription rates and mRNA levels fell during the first 3 weeks
      after birth, and albumin expression rose slightly. Analysis of chromatin
      structure around the IGF-I gene revealed 15 DNase I-hypersensitive sites in adult
      rat liver in the 120 kilobases (kb) comprising the 6 exon gene and its flanking
      regions (8 sites within 10 kb at the 5'-end including exons 1-3, 5 sites in the
      50-kb third intron, and 2 sites in the 15-kb fifth intron). During development
      there was a progressive appearance of DNase I-hypersensitive sites that coincided
      with activation of IGF-I gene expression. One site that became fully
      hypersensitive by postnatal day 7 was mapped by in vivo DNAse I footprinting to
      the proximal 200 nucleotides of promoter 1. Since serum IGF-I values rose from 10
      to 120 micrograms/liter during the initial postnatal week, these results indicate
      that transcriptional mechanisms are principally responsible for the stimulation
      of IGF-I synthesis that occurs shortly after birth. Because discrete changes in
      chromatin organization coincided with induction of IGF-I gene transcription, it
      is likely that a series of developmentally modulated transcription factors are
      involved the activation process.

PMID- 1400463
TI  - Inhibition of eukaryotic DNA polymerase alpha with a novel lysophosphatidic acid
      (PHYLPA) isolated from myxoamoebae of Physarum polycephalum.
AB  - A specific inhibitor of DNA polymerase alpha was isolated from the lipid fraction
      prepared from myxoamoebae of a true slime mold, Physarum polycephalum. The
      purified substance was subjected to structural studies by fast atom bombardment
      mass spectroscopy, infrared spectroscopy, and two-dimensional nuclear magnetic
      resonance spectroscopy. The structure of this substance was thereby suggested to
      be a novel lysophosphatidic acid (LPA) composed of cyclic phosphate and
      cyclopropane-containing hexadecanoic acid. Then we named this substance PHYLPA
      (Physarum LPA). PHYLPA inhibited more than 80% of the affinity-purified calf
      thymus DNA polymerase alpha activity at a concentration of 10 micrograms/ml
      (approximately 20 microM). Inhibition was observed for DNA polymerase alpha but
      not for DNA polymerase beta or gamma from various eukaryotic species, nor did it
      inhibit DNA polymerase I from E. coli. From kinetic analyses, the inhibition was
      considered to be caused by the interaction of PHYLPA with the template DNA.

PMID- 1400464
TI  - Identification of C8-methylguanine in the hydrolysates of DNA from rats
      administered 1,2-dimethylhydrazine. Evidence for in vivo DNA alkylation by methyl
      radicals.
AB  - C8-Methylguanine was identified in the neutral hydrolysates of DNA isolated from
      the liver or colon tissue of rats administered 1,2-dimethylhydrazine. In all the
      samples examined, the biologically isolated adducts were characterized by co
      elution with synthetic C8-methylguanine under different high pressure liquid
      chromatography conditions. The sample isolated from liver DNA was also identified
      by UV spectroscopy at different pH values and by mass spectrometry. The estimated
      yields of C8-methylguanine obtained in hydrolysates of DNA from the liver or
      colon tissue were comparable to those of O6-methylguanine. C8-Methylguanine was
      not detected when the spin trap alpha-(4-pyridyl-1-oxide)-N-tert- butylnitrone
      was administered together with 1,2-dimethylhydrazine. The spin trap also
      inhibited N7-methylguanine and O6-methylguanine yields, although to a lesser
      extent. These results constitute the first evidence that DNA alkylation by carbon
      centered radicals can occur in vivo.

PMID- 1400465
TI  - Characterization of oligomers as kinetic intermediates in myosin subfragment 1
      induced polymerization of G-actin.
AB  - The nature of the kinetic intermediates involved in S1-induced polymerization of
      G-actin into F-acto-S1-decorated filaments has been investigated using as probes
      light scattering, the fluorescence of pyrenyl- or NBD-labeled actin, and the
      anisotropy of fluorescence of N-iodoacetyl-N'-(5-sulfo-1-napthyl)ethylene diamine
      (AEDANS)-labeled actin. With AEDANS-G-actin, the initial formation of a ternary
      G2S complex between two G-actin and one S1 molecules (Valentin-Ranc, C., Combeau,
      C., Carlier, M. F., and Pantaloni, D. (1991) J. Biol. Chem. 266, 17871-17879) has
      been confirmed. Data obtained with all probes are consistent with the subsequent
      rapid formation of G-actin-S1 oligomers in which the actin/S1 molar ratio is 2:1.
      Oligomers form above 0.6 microM G-actin with S1(A1) and above 3.5 microM G-actin
      with S1(A2), at 20 degrees C. Oligomerization is endothermic with a delta H of 14
      kcal/mol. A tentative model is proposed to comprehensively account for the data
      and the structural features of the F-actin-S1 filament. Within this model,
      longitudinal actin-actin interactions take place in G2S, and lateral, hydrophobic
      actin-actin interactions appear upon formation of (G2S)n oligomers.

PMID- 1400466
TI  - Tyrosine phosphatase activity of lymphoma CD45 (GP180) is regulated by a direct
      interaction with the cytoskeleton.
AB  - GP180 is one of the major transmembrane glycoproteins in mouse T-lymphoma cells.
      This molecule is an isoform of CD45 and is known to contain an intrinsic protein
      tyrosine phosphatase (PTPase) activity. Using several complementary biochemical
      techniques, we have found that fodrin (a spectrin-like protein) is preferentially
      co-isolated with CD45 (GP180), suggesting that a complex between CD45 (GP180) and
      the cytoskeleton exists in mouse T-lymphoma cells. Furthermore, we have
      determined that this CD45 (GP180)-fodrin complex is dissociated by high salt
      treatment. Using in vitro binding assays, we have shown that CD45 (GP180) binds
      directly and specifically to fodrin (Kd approximately 1.1 nM) or spectrin (Kd
      approximately 3.2 nM) in a saturable manner. Additional analyses indicate that a
      48-kDa phosphopeptide of CD45 (GP180) contains the fodrin/spectrin-binding
      domain. Most importantly, the direct binding of fodrin/spectrin to CD45 (GP180)
      is found to significantly stimulate the PTPase activity of CD45. Enzyme kinetic
      analysis indicates that fodrin and spectrin increase the Vmax of CD45 (GP180)
      mediated dephosphorylation by 7.5 and 3.2-fold, respectively, without
      significantly changing the Km value. These results strongly suggest that the
      cytoskeletal proteins, fodrin and spectrin, play an important role in the
      regulation of the CD45 (GP180) PTPase activity during lymphocyte activation.

PMID- 1400469
TI  - Fluoride-inhibited calcium ATPase of sarcoplasmic reticulum. Magnesium and
      fluoride stoichiometry.
AB  - The sarcoplasmic reticulum (SR) CaATPase is inactivated by fluoride in the
      presence of magnesium (Murphy, A. J., and Coll, R. J. (1992) J. Biol. Chem. 267,
      5229-5235). The inactive complex is very stable and can be isolated free of other
      components by 48 h of dialysis at 4 degrees C (Murphy, A. J., and Coll, R. J.
      (1992) J. Biol. Chem. 267, 16990-16994). In this study, we used a fluoride
      specific electrode to determine that the amount of tightly bound fluoride in the
      complex was 9.4 +/- 2 nmol mg-1 SR protein. The rate constant of inactivation was
      very similar to the rate constant of fluoride incorporation and varied directly
      as the square of the fluoride concentration. Luminal Ca2+ accelerated
      reactivation of the inhibited enzyme, and the rate constants of activity regain
      and fluoride release were very similar. Although required for inhibition, added
      magnesium did not accelerate reactivation. Analysis for magnesium using
      antipyrylazo III of the inhibited enzyme showed 4.1 +/- 0.4 nmol mg-1 SR protein.
      As there is much evidence in the literature supportive of an estimate of calcium
      pumps equal to approximately 4-5 nmol mg-1 SR protein, our results indicate that
      each inhibited enzyme contains two tightly bound fluorides and one tightly bound
      magnesium.

PMID- 1400468
TI  - Site-directed mutagenesis reveals the involvement of an additional thioredoxin
      dependent regulatory site in the activation of recombinant sorghum leaf NADP
      malate dehydrogenase.
AB  - The chloroplastic enzyme NADP-malate dehydrogenase is activated by a reversible
      thiol/disulfide interchange with reduced thioredoxin. Its target disulfide bridge
      is considered to be located at the amino terminus. To further substantiate the
      regulatory role of this disulfide, site-directed mutagenesis has been used to
      replace each or both of the amino-terminal cysteines of the sorghum leaf NADP
      malate dehydrogenase, expressed in Escherichia coli, by serines. A truncation
      mutant lacking the amino terminus has also been produced. Surprisingly, the
      mutant proteins still required activation by reduced thioredoxin. However, their
      activation was almost instantaneous, whereas the native enzyme reached full
      activity after a 10-20 min preincubation. The 8 1/2 for reduced thioredoxin was
      decreased 2-fold in the mutants, but their Km values for NADPH and oxaloacetate
      did not change significantly. The inhibition of activation by NADP and inhibition
      of activity by thiol-derivatizing agents were also retained. These results are
      interpreted as an indication that two thioredoxin-dependent reduction steps are
      involved in NADP-dependent malate dehydrogenase light activation, hence that two
      disulfides per monomer participate in the process. The overall activation rate
      would depend on a conformational change following the reduction of the amino
      terminal disulfide bridge. The amino terminus also plays a role in the
      dimerization of the protein.

PMID- 1400467
TI  - Cloning and characterization of a cysteine proteinase from Saccharomyces
      cerevisiae.
AB  - We have isolated a gene from Saccharomyces cerevisiae that encodes a protein
      homologous to the mammalian cysteine proteinase bleomycin hydrolase. Sequence
      comparison between the yeast and rabbit proteins indicates an amino acid identity
      of 41.5% over 277 residues and a similarity of 78.3% when conservative
      substitutions are included. The apparent mass of the yeast protein by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis is 47 kDa, although sequence
      analysis indicates two potential initiator methionines that suggest calculated
      masses of either 51 or 55 kDa. The protein is nonessential in yeast as haploid
      mutants disrupted at several positions along the open reading frame remain
      viable. Furthermore, these mutants do not exhibit any readily observable growth
      defects under varying conditions of temperature, nutrients, osmotic strength, or
      exogenous bleomycin. However, the purified protein does exhibit marked hydrolytic
      activity toward the substrate arginine 4-methyl-7-coumarylamide (Km = 12.8
      microM, Vmax = 2.56 mumol mg-1 h-1), and yeast cells engineered to express this
      protein at higher levels maintain increased resistance to bleomycin compared to
      wild-type cells. Because this protein represents the first example of a cysteine
      proteinase identified in yeast, we have named it Ycp1 (yeast cysteine
      proteinase).

PMID- 1400470
TI  - Regulated, but not constitutive, secretory proteins bind porcine
      chymotrypsinogen.
AB  - Endocrine and exocrine cells exhibit both a constitutive and a regulated
      secretory pathway. In the latter pathway, secretory proteins are stored at a high
      concentration in secretory granules and are released by exocytosis in response to
      appropriate external stimuli. Sorting between the two secretory pathways is
      believed to take place in the trans-Golgi tubular network. To account for
      experimental data, it has been proposed that sorting receptors exist which bind a
      variety of regulated secretory proteins, including foreign secretory proteins
      introduced into the cells by transfection. In support of the sorting receptor
      hypothesis Chung et al. (Chung, K.-N., Walter, P., Aponte, G. W., and Moore, H.
      P.H. (1989) Science 243, 192-197) isolated a group of 25-kDa canine pancreatic
      "hormone-binding proteins" that bound regulated but not constitutive secretory
      proteins. To determine if similar proteins are present in other species and
      tissues, we have screened porcine pancreas, parathyroid, adrenal medulla, and
      pituitary glands. A 31-kDa protein, similar to that identified by Chung et al.
      (1989), which binds to regulated but not to constitutive secretory proteins was
      identified in porcine pancreas. This protein was not detected in the parathyroid,
      adrenal medulla, or pituitary glands, however, which argues against it serving as
      a general sorting receptor. NH2-terminal sequencing, immunoreactivity, and
      proteolytic activity data indicate that the porcine 31-kDa protein is similar if
      not identical to porcine chymotrypsinogen A or B.

PMID- 1400471
TI  - Nerve growth factor stimulates the tyrosine phosphorylation of a 38-kDa protein
      that specifically associates with the src homology domain of phospholipase C
      gamma 1.
AB  - The cellular actions of nerve growth factor (NGF) involve changes in protein
      phosphorylation, initiated by the binding and subsequent activation of its
      tyrosine kinase receptor, the trk protooncogene (pp140c-trk). Upon exposure to
      NGF, a 38-kDa tyrosine-phosphorylated protein (pp38) is identified in both PC-12
      pheochromocytoma cells and NIH3T3 cells transfected with the full-length human
      pp140c-trk cDNA (3T3-c-trk) that is specifically coimmunoprecipitated with pp140c
      trk or phosphatidylinositol-phospholipase C (PLC)-gamma 1. In both PC-12 and 3T3
      c-trk cells, NGF rapidly stimulates the association of pp140c-trk and pp38 with a
      fusion protein containing the src homology (SH) domains of PLC gamma 1. This
      phosphorylation and subsequent association are specific for NGF, since epidermal
      growth factor, platelet-derived growth factor, and insulin do not stimulate the
      tyrosine phosphorylation of these proteins or their association with the PLC
      gamma 1 SH domains, although the receptors for these growth factors do undergo
      tyrosine phosphorylation and association with the PLC-gamma 1 fusion protein
      under these conditions. Furthermore, the NGF-dependent pp38-SH binding is
      specific for the SH2 domains of PLC-gamma 1, since the phosphoprotein does not
      bind to fusion proteins containing SH domains of ras GTPase-activating protein or
      the p85 subunit of phosphatidylinositol 3 kinase. Both amino- and carboxyl
      terminal SH2 domains of PLC-gamma 1 are necessary for the association of pp38
      with PLC-gamma 1, although each SH2 domain is sufficient for the association of
      pp140c-trk with PLC-gamma 1. In both PC-12 and 3T3-c-trk cells, the
      phosphorylation and association of pp38 with PLC gamma 1 is rapid, occurring
      maximally at 1 min and declining thereafter. Moreover, this effect of NGF is dose
      dependent over a physiological concentration of the growth factor. The
      specificity and rapidity of pp38 phosphorylation and its association with PLC
      gamma 1 suggest that it may be an important component in signal transduction for
      NGF.

PMID- 1400472
TI  - The induction by human interleukin-6 of apoptosis in the promonocytic cell line
      U937 and human neutrophils.
AB  - Apoptosis of neutrophils at sites of inflammation in vivo is thought to lead to
      their recognition and safe elimination by macrophages. Little is known, however,
      about the regulation of apoptosis in myeloid cells. We report here that the human
      promonocytic leukemic cell line, U937, and mature human neutrophils can be
      induced to become apoptotic when cultured with interleukin-6. Apoptosis of U937
      cells, assessed morphologically and by the presence of DNA fragmentation, was
      increased significantly in a dose-dependent fashion by concentrations of 0.5-100
      ng/ml interleukin-6. Apoptosis of U937 cells was evident after 48 h of incubation
      with 20 ng/ml interleukin-6, and the effect was eliminated by adsorption of
      interleukin-6 with a specific monoclonal antibody. Apoptosis was not evident in
      the presence of the differentiating agent phorbol 12-myristate 13 acetate; the
      induction of apoptosis in U937 cells was not therefore a consequence of
      differentiation. Apoptosis of mature neutrophils was enhanced after 24 h in
      culture with interleukin-6. Interleukin-6 might be an important factor in the
      normal resolution of inflammation through the induction of apoptosis of
      neutrophils.

PMID- 1400473
TI  - Expression of human apolipoprotein A-II and its effect on high density
      lipoproteins in transgenic mice.
AB  - Apolipoproteins A-I and A-II comprise approximately 70 and 20%, respectively, of
      the total protein content of HDL. Evidence suggests that apoA-I plays a central
      role in determining the structure and plasma concentration of HDL, while the role
      of apoA-II is uncertain. To help define the function of apoA-II and determine
      what effect increasing its plasma concentration has on HDL, transgenic mice
      expressing human apoA-II and both human apoA-I and human apoA-II were produced.
      Human apoA-II mRNA is expressed exclusively in the livers of transgenic animals,
      and the protein exists as a dimer as it does in humans. High level expression of
      human apoA-II did not increase HDL concentrations or decrease plasma
      concentrations of murine apoA-I and apoA-II in contrast to what was observed in
      mice overexpressing human apoA-I. The primary effect of overexpressing human apoA
      II was the appearance of small HDL particles composed exclusively of human apoA
      II. HDL from mice transgenic for both human apoA-I and human apoA-II displayed a
      unique size distribution when compared with either apoA-I or apoA-II transgenic
      mice and contain particles with both these human apolipoproteins. These results
      in mice, indicating that human apoA-II participates in determining HDL size,
      parallel results from human studies.

PMID- 1400474
TI  - Differential stimulation of protein kinase C activity by phorbol ester or
      calcium/phosphatidylserine in vitro and in intact synaptosomes.
AB  - Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) was
      compared with calcium/phosphatidylserine (Ca/PS). The substrate specificity of
      PKC was more limited with PS/PMA. Substrates could be divided into three
      overlapping groups according to their relative level of phosphorylation: C1,
      relatively preferred substrates with Ca/PS, included dephosphin, histone, and
      peptide GS1-10. C2, relatively preferred with PS/PMA, included myelin basic
      protein and MARCKS. C3, substrates independent of activators. PS/PMA altered the
      Vmax of PKC for substrate, and decreased the Km for Mg2+. Differential substrate
      phosphorylation by PS/PMA also occurred for PKC isozymes resolved by
      hydroxylapatite chromatography and was most dramatic for PKC-alpha, which could
      no longer phosphorylate histone or GS1-12. Differential activities of PKC were
      also observed in synaptosol and in intact synaptosomes where PMA stimulated
      phosphorylation of MARCKS, but not dephosphin. It was further shown that
      dephosphin was indeed a substrate of PKC in the intact synaptosomes by use of a
      repolarization-dependent dephosphin phosphorylation assay. The differential PKC
      activities could also be distinguished by inhibitors. H-7 was equipotent,
      palmitoylcarnitine did not inhibit in vitro C2 phosphorylation, but inhibited
      dephosphin in intact synaptosomes, and sphingosine did not inhibit C1 substrates
      and was without effect on dephosphin in intact synaptosomes. Therefore PS/PMA
      alters or limits the substrate specificity of PKC, leading to a differential
      substrate phosphorylation in vitro and in intact synaptosomes and differential
      inhibitor sensitivity. The pattern of protein phosphorylation observed after PKC
      activation in intact cells will therefore be dependent upon the activator.

PMID- 1400476
TI  - Primary structure of the alanine carrier protein of thermophilic bacterium PS3.
AB  - Purified alanine carrier proteins were cleaved into peptides either chemically
      after solubilization in 1,1,1,3,3,3-hexafluoro-2-propanol or proteolytically with
      lysylendopeptidase. From the amino acid sequence analyses of these peptides, we
      synthesized a DNA probe and utilized it for successful cloning of a gene encoding
      the alanine carrier protein (acp gene). The 5'-flanking region was determined by
      an inverse polymerase chain reaction, and an open reading frame consisting of
      1,335 nucleotides was found. The amino acid sequence deduced from the open
      reading frame consists of 445 amino acids, and all the partial amino acid
      sequences determined are included in the sequence. Although the calculated M(r)
      of 47,803 is significantly larger than the apparent M(r) of 42,500 as reported
      previously (Hirata, H., Kambe, T., and Kagawa, Y. (1984) J. Biol. Chem. 259,
      10653-10656), an in vitro translation experiment revealed that the product of the
      acp gene migrates at a position coinciding with that of the purified alanine
      carrier. Hydropathy analysis suggests that the protein contains at least 8
      hydrophobic segments presumably spanning membrane. A homology search on a
      database reveals relatively high scores of homology with either the Escherichia
      coli melibiose carrier or the human Na+/glucose symporter, particularly in the
      region from Leu246 to Glu286. Furthermore, the region also reveals low but
      significant similarities to other Na(+)-coupled symporters.

PMID- 1400475
TI  - Purification and characterization of mitochondrial imidazoline-guanidinium
      receptive site from rabbit kidney.
AB  - The imidazoline-guanidinium receptive site (IGRS) is a membrane-bound protein
      that may mediate some of the pharmacological effects of imidazoline and
      guanidinium compounds. The structure and functionality of this protein are
      unknown but, in addition to its location at the plasma membrane, it is found in
      high density in the outer membrane of mitochondria (Tesson, F., Prip-Buus, C.,
      Lemoine, A., Pegorier, J.-P., and Parini, A. (1991) J. Biol. Chem. 266, 155-160).
      Using a two-step procedure, we report the purification of mitochondrial IGRS from
      rabbit kidney to the apparent homogeneity. After solubilization of mitochondrial
      membranes with digitonin, an apparently homogeneous IGRS preparation was obtained
      by two sequential purification steps, chromatofocusing and hydroxylapatite
      agarose chromatography. One- and two-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analysis of the purified preparation after
      silver staining or radioiodination indicated that IGRS binding subunit was
      purified at the apparent homogeneity since a single band (M(r) approximately
      60,000) was observed. IGRS behaves as an acidic protein (pI 5.5) whose binding
      activity is regulated by H+ concentration near a physiological pH of 7.4. The
      ability to achieve rapid purification of IGRS should facilitate efforts to define
      molecular properties and functionality of this protein.

PMID- 1400477
TI  - Evidence for two distinct major protein components, PAR 1 and PAR 2, in the
      paraflagellar rod of Trypanosoma cruzi. Complete nucleotide sequence of PAR.
AB  - The previously identified major protein components of the paraflagellar rod in
      Trypanosoma cruzi, PAR 1 and PAR 2, were analyzed to determine if they are
      distinct proteins or different conformations of a single polypeptide as has been
      suggested for other trypanosomatids. Amino acid sequence analysis showed PAR 1
      and PAR 2 to be two distinct polypeptides. Antibodies specific against either PAR
      1 or PAR 2 were shown to each react with a distinct band in Western blots of
      paraflagellar isolates of T. cruzi and other trypanosomatids if rigorous protease
      inhibition was used. The PAR 2 message was isolated and characterized by Northern
      blot and nucleic acid sequence analysis. Preliminary analysis of the PAR 2 gene
      indicates that PAR 2 is a member of a multigene family with all members residing
      on a single chromosome.

PMID- 1400478
TI  - Nerve growth factor-activated protein kinase N. Characterization and rapid near
      homogeneity purification by nucleotide affinity-exchange chromatography.
AB  - Protein kinase N (PKN) is a protein kinase rapidly activated by nerve growth
      factor (NGF) and other agents in PC12 pheochromocytoma and additional cell types.
      PKN is selectively inhibited by purine analogs, and this property has served both
      as a diagnostic for PKN activity and to establish its apparent involvement in
      certain pathways of the NGF mechanism of action. The present work has focused on
      further characterization, identification, and purification of NGF-activated PKN.
      We show here that PKN can be substantially enriched by elution from ion exchange
      resins with ATP. We exploited this novel technique (nucleotide affinity exchange
      chromatography) to devise two alternative isolation schemes for PKN. One utilizes
      sequential chromatographic steps and provides a preparation that is apparently
      60% homogeneous for PKN and represents a total enrichment of approximately 10,000
      fold. The other is a single column procedure and includes prewashes with NAD.
      This method yields material that is about 5-10% homogeneous for PKN, requires
      about 1 h, and can be applied to multiple samples in parallel. The ATP elution
      technique furthermore distinguishes NGF-regulated from basal PKN activity and
      thereby suggests the presence of distinct PKN isoforms. The applications of
      sucrose gradient centrifugation, gel filtration chromatography, sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/silver staining, affinity
      labeling with 8-azido-ATP/SDS-PAGE, and autophosphorylation (after SDS-PAGE,
      blotting and renaturation) all indicate that PKN has an apparent molecular mass
      of 45-47 kDa and is mainly monomeric in solution. These and additional properties
      appear to distinguish PKN from many previously described protein kinases.

PMID- 1400479
TI  - Purification and initial characterization of the proteasome from the higher plant
      Spinacia oleracea.
AB  - The proteasome (multicatalytic protease complex), a high molecular weight protein
      complex, has been purified from spinach leaves by successive chromatography on
      DEAE-cellulose, Bio-Gel A-1.5m, DEAE-TOYOPEARL 650C, and DEAE-5PW. The molecular
      mass was estimated to be 850 kDa by gel filtration. Polyacrylamide gel
      electrophoresis of the proteasome gave a single protein band under nondenaturing
      conditions and at least 10 bands in the range of 21-32 kDa in the presence of
      sodium dodecyl sulfate. By electron microscopy after negative staining with
      uranyl acetate, the proteasome from spinach appeared as symmetrical ring-shaped
      particles. The substrate specificity of proteasomes indicates that they contain
      at least three types of activity, namely, chymotrypsin-like, Staphylococcus
      aureus V8 protease-like, and trypsin-like activities. The former two activities
      were enhanced by poly-L-lysine or sodium dodecyl sulfate. Moreover, we examined
      the immunological reactivities of proteasomes from various eukaryotes. As a
      result, cross-immunoreactivities of some subunits were observed. These properties
      of the proteasome are similar to those of proteasomes isolated from various other
      eukaryotic sources.

PMID- 1400480
TI  - Nuclear-encoded tobacco chloroplast ribosomal protein L24. Protein
      identification, sequence analysis of cDNAs encoding its cytoplasmic precursor,
      and mRNA and genomic DNA analysis.
AB  - Using a Nicotiana tabacum leaf cDNA library in the expression vector lambda gt11,
      two cDNAs encoding the full-length precursor polypeptide (M(r) 20,696) of tobacco
      chloroplast ribosomal protein L24 were identified and sequenced. These cDNAs
      encode a mature protein of 146 amino acids (M(r) 16,418) with a transit peptide
      of 41 amino acids (M(r) 4,278). The mature tobacco L24 protein has 78, 65, 45,
      and 35% sequence identity with ribosomal proteins L24 of pea, spinach, Bacillus
      subtilis, and Escherichia coli, respectively. The transit peptide of tobacco L24
      is 54 and 57% identical with that of L24 chloroplast ribosomal proteins of pea
      and spinach, respectively. An expressed beta-galactosidase:L24 fusion protein,
      bound to nitrocellulose filters, was used as affinity matrix to purify
      monospecific antibody to L24 protein. Using this monospecific antibody protein
      L24 was identified among high performance liquid chromatography (HPLC)-purified
      tobacco chloroplast ribosome 50 S subunit proteins. The predicted amino terminus
      of the mature L24 protein was confirmed by partial sequencing of the HPLC
      purified L24 protein. Northern blot analysis revealed a single mRNA band (0.85
      0.90 kilobase) corresponding in size to full-length L24 cDNA. The presence of
      multiple genes for L24 is suggested by Southern blot hybridization and
      characterization of two cDNAs for L24 which only differ in their 3'-noncoding
      sequences.

PMID- 1400481
TI  - Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080
      human fibrosarcoma cells. Purification and activation of the precursor and
      enzymic properties.
AB  - Matrix metalloproteinase 9 (MMP-9) has been purified as an inactive zymogen of
      M(r) 92,000 (proMMP-9) from the culture medium of HT 1080 human fibrosarcoma
      cells. The NH2-terminal sequence of proMMP-9 is Ala-Pro-Arg-Gln-Arg-Gln-Ser-Thr
      Leu-Val-Leu-Phe-Pro, which is identical to that of the 92-kDa type IV
      collagenase/gelatinase. The zymogen can be activated by 4-aminophenylmercuric
      acetate, yielding an intermediate form of M(r) 83,000 and an active species of
      M(r) 67,000, the second of which has a new NH2 terminus of Met-Arg-Thr-Pro-Arg
      (Cys)-Gly-Val-Pro-Asp-Leu-Gly-Arg-Phe-Gln-Thr- Phe-Glu. Immunoblot analyses
      demonstrate that this activation process is achieved by sequential processing of
      both NH2- and COOH-terminal peptides. TIMP-1 complexed with proMMP-9 inhibits the
      conversion of the intermediate form to the active species of M(r) 67,000. The
      proenzyme is fully activated by cathepsin G, trypsin, alpha-chymotrypsin, and MMP
      3 (stromelysin 1) but not by plasmin, leukocyte elastase, plasma kallikrein,
      thrombin, or MMP-1 (tissue collagenase). During the activation by MMP-3, proMMP-9
      is converted to an active species of M(r) 64,000 that lacks both NH2- and COOH
      terminal peptides. In addition, HOCl partially activates the zymogen by reacting
      with an intermediate species of M(r) 83,000. The enzyme degrades type I gelatin
      rapidly and also cleaves native collagens including alpha 2 chain of type I
      collagen, collagen types III, IV, and V at undenaturing temperatures. These
      results indicate that MMP-9 has different activation mechanisms and substrate
      specificity from those of MMP-2 (72-kDa gelatinase/type IV collagenase).

PMID- 1400482
TI  - Cytochrome P-450 arachidonic acid epoxygenase. Regulatory control of the renal
      epoxygenase by dietary salt loading.
AB  - The rat kidney microsomal epoxygenase catalyzed the asymmetric epoxidation of
      arachidonic acid to generate as major products: 8(R),9(S)-, 11(R),12(S)- and
      14(S),15(R)-epoxyeicosatrienoic acids with optical purities of 97, 88, and 70%,
      respectively. Inhibition studies utilizing a panel of polyclonal antibodies to
      several rat liver cytochrome P-450 isoforms, indicated that the renal
      epoxygenase(s) belongs to the cytochrome P-450 2C gene family. Dietary salt,
      administered either as a 2-2.5% (w/v) solution in the drinking water or as a
      modified solid diet containing 8% NaCl (w/w), resulted in marked and selective
      increases in the renal microsomal epoxygenase activity (416 and 260% of controls,
      for the liquid and solid forms of NaCl, respectively) with no significant changes
      in the microsomal omega/omega-1 oxygenase or in the hepatic arachidonic acid
      monooxygenase reaction. Immunoblotting studies demonstrated that dietary salt
      induced marked increases in the concentration of a cytochrome P-450 isoform(s)
      recognized by polyclonal antibodies raised against human liver cytochrome P-450
      2C10 or rat liver cytochrome P-450 2C11. Comparisons of the stereochemical
      selectivity of the induced and non-induced microsomal epoxygenase(s) with that of
      purified rat liver cytochrome P-450 2C11 suggest that the salt-induced protein(s)
      is catalytically and structurally different from liver cytochrome P-450 2C11. The
      in vivo significance of dietary salt in regulating the activities of the kidney
      endogenous arachidonic acid epoxygenase was established by the demonstration of a
      salt-induced 10-20-fold increase in the urinary output of epoxygenase
      metabolites. These results, in conjunction with published evidence demonstrating
      the potent biological activities of its metabolites, suggest a role for the
      epoxygenase in the renal response to dietary salt.

PMID- 1400483
TI  - Identification of B beta chain domains involved in human fibrinogen assembly.
AB  - Fibrinogen chains are assembled in a stepwise manner in the rough endoplasmic
      reticulum prior to secretion of the final six-chain dimeric molecule. Previous
      studies indicated that the synthesis of B beta may be a rate-limiting factor in
      the assembly of human fibrinogen. To determine the domains of B beta which
      interact with the other two component chains of fibrinogen, deletion mutants of B
      beta were transiently co-expressed, together with A alpha and gamma chains, in
      COS cells, and fibrinogen assembly and secretion were measured. Deletion of the
      COOH-terminal half of the B beta chain (amino acids 208-461) did not affect
      assembly and secretion. Assembly of A alpha, gamma, and B beta also occurred when
      the first NH2-terminal 72 amino acids of B beta were deleted, but not when 93
      amino acids were deleted. This indicates that the B beta domain between amino
      acids 73 and 93 is necessary for the assembly of the three fibrinogen chains.
      This domain marks the start of the alpha-helical "coiled-coil" region of
      fibrinogen.

PMID- 1400484
TI  - The role of the cathepsin D propeptide in sorting to the lysosome.
AB  - The propeptides of lysosomal enzymes have been implicated in membrane association
      and mannose 6-phosphate-independent sorting to the lysosome (Rijnboutt, S.,
      Aerts, H., Geuze, H. J., Tager, J. M., and Strous, G. J. (1991) J. Biol. Chem.
      266, 4862-4868; McIntyre, G. F., and Erickson, A. H. (1991) J. Biol. Chem. 266,
      15438-15445). In this report, the function of the propeptide of procathepsin D in
      sorting to the lysosome was directly assessed using a cathepsin D deletion mutant
      lacking the propeptide, and using a chimeric cDNA encoding the cathepsin D
      propeptide fused to the secretory protein alpha-lactalbumin. Proteins encoded by
      these cDNAs were expressed in mouse Ltk- cells and in human hepatoma Hep G2
      cells, and then immunoprecipitated and analyzed by SDS-polyacrylamide gel
      electrophoresis. The deletion mutant was glycosylated but was rapidly degraded in
      a chloroquine-independent fashion and did not assume an active conformation. Thus
      the propeptide appeared to be necessary for correct folding. The chimeric protein
      was glycosylated and secreted. The coincidence of complex oligosaccharide
      modification and secretion of the chimeric protein suggested that it was slowly
      released from the endoplasmic reticulum and rapidly passed through the cell to
      the extracellular compartment. This was confirmed by immunofluorescent
      localization of the proteins. The data indicated that the propeptide appeared to
      be necessary for folding of cathepsin D but, unlike the yeast vacuolar
      propeptides, was not sufficient to direct a secretory protein to the lysosome in
      fibroblasts or in epithelial cells.

PMID- 1400485
TI  - Binding of the metalloregulatory protein DtxR to the diphtheria tox operator
      requires a divalent heavy metal ion and protects the palindromic sequence from
      DNase I digestion.
AB  - Transcription of the corynebacteriophage diphtheria tox operon has been shown to
      be regulated through a corynebacterial determined factor DtxR. The dtxR gene has
      been recently cloned and expressed in Escherichia coli, and shown to regulate the
      expression of beta-galactosidase expression from a diphtheria tox
      promoter/operator-lacZ transcriptional fusion. Tao et al. (Tao, X., Boyd, J., and
      Murphy, J. R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 5897-5901) have recently
      shown by gel mobility shift assay that the binding of DtxR to the tox operator
      requires a divalent heavy metal ion, as well as the 27-base pair interrupted
      palindromic sequence. We now show the activation of DtxR in the presence of Co2+,
      Fe2+, or Mn2+ results in the protection of a 33- and 27-nucleotide region on the
      coding and non-coding strand from DNase I digestion, respectively. DtxR is also
      activated in the presence of Ni2+; however, this metalloregulatory factor is only
      weakly activated by Zn2+. The diphtheria tox regulatory region protected from
      DNase I digestion in the presence of activated DtxR encompasses the 27-base pair
      interrupted palindromic sequence.

PMID- 1400486
TI  - Statin, a protein specifically present in nonproliferating cells, is a
      phosphoprotein and forms a complex with a 45-kilodalton serine/threonine kinase.
AB  - The protein statin is found in nuclei of nonproliferating cells. Here we report
      that statin is a phosphoprotein, phosphorylated at serine residues in cultured
      cells. During immunoprecipitation with anti-statin (S44) antibody, a 45-kDa
      protein co-precipitates with the 57-kDa statin. In vitro kinase assays
      demonstrate that the S44 immunoprecipitates can phosphorylate, besides statin,
      immunoglobulins, enolase, and casein, at either serine or serine/threonine
      residues. Kinase assays with immunoprecipitated proteins performed on casein- or
      enolase-impregnated gels show that these substrates are phosphorylated by the 45
      kDa (p45) protein. When the S44 immunoprecipitates from human cultured
      fibroblasts with different in vitro life-spans were compared, the p45 kinase
      activity was present only in young nongrowing and senescent cells, but not in
      young growing ones. In other cell cultures, the kinase is detected only in
      protein complexes precipitated from quiescent 3T3 cells, but not from cycling 3T3
      cells or from transformed human glioma (U251-4) cells. Cell fractionation
      studies, indicating that the phosphorylating activity of S44 immunoprecipitates
      correlates both qualitatively and quantitatively with the amount of statin
      present, provide strong evidence that in vivo statin is specifically associated
      with the p45 kinase. These results suggest that the nonproliferation-specific
      nature of statin is indeed related to the phosphorylated property of this protein
      and maybe contributed by the associated kinase.

PMID- 1400487
TI  - Assembly of the oligomeric membrane pore formed by Staphylococcal alpha-hemolysin
      examined by truncation mutagenesis.
AB  - The alpha-hemolysin (alpha HL) from Staphylococcus aureus causes the lysis of
      susceptible cells such as rabbit erythrocytes (rRBCs). Lysis is associated with
      the formation of a hexameric pore in the plasma membrane. Here we show that
      truncation mutants of alpha HL missing 2 to 22 N-terminal amino acids form
      oligomers on the surfaces of rRBCs but fail to lyse the cells. By contrast,
      mutants missing 3 or 5 amino acids at the C terminus are very inefficient at
      oligomerization but do lyse rRBCs, albeit extremely slowly. The C-terminal
      truncation mutants, retarded as monomers on the cell surface, undergo a
      conformational change in which the protease-sensitive loop located near the
      midpoint of the polypeptide chain becomes occluded. Judged by this criterion,
      polypeptides truncated at the N terminus, frozen as nonlytic oligomers, are in a
      similar conformation. A second proteolytic site near the N terminus of the
      polypeptide becomes inaccessible in the lytic pore formed by the wild-type
      polypeptide, supporting the idea that a second conformational change occurs upon
      pore formation. These findings suggest a pathway for assembly of the lytic pore
      in which alpha HL first binds to target cells as a monomer, which is converted to
      a nonlytic oligomeric intermediate before formation of the pore. In keeping with
      this model, an N-terminal truncation mutant blocks the slow lysis induced by a C
      terminal truncation mutant, presumably by diverting the weakly lytic subunits
      into inactive oligomers.

PMID- 1400488
TI  - Molecular analysis of dibasic endoproteolytic cleavage signals.
AB  - Biologically active peptide hormones are synthesized from larger precursor
      proteins by a variety of post-translational processing reactions. To characterize
      these processing reactions further we have expressed preprogastrin in two
      endocrine cell lines and examined the molecular determinants involved in
      endoproteolysis at dibasic cleavage sites. The Gly93-Arg94-Arg95 carboxyl
      terminal processing site of progastrin must be processed sequentially by an
      endoprotease, a carboxypeptidase, and an amidating enzyme to produce bioactive
      gastrin. For these studies the dibasic Arg94-Arg95 residues that serve as signals
      for the initiation of this processing cascade were mutated to Lys94-Arg95, Arg94
      Lys95, and Lys94-Lys95. In the GH3 cells the Lys94-Arg95 mutation slightly
      diminished synthesis of carboxyl-terminally amidated gastrin, whereas in the MTC
      6-23 cells this mutation had no effect on amidated gastrin synthesis. In
      contrast, both Arg94-Lys95 and Lys94-Lys95 mutations resulted in significantly
      diminished production of amidated gastrin in both cell lines. A specific
      hierarchy of preferred cleavage signals at this progastrin processing site was
      demonstrated in both cell lines, indicating that cellular dibasic endoproteases
      have stringent substrate specificities. Progastrins with the Lys94-Arg95 mutation
      in GH3 cells also demonstrated diminished processing at the Lys74-Lys75 dibasic
      site, thus single amino acid changes at one processing site may alter cleavage at
      distant sites. These studies provide insight into the post-translational
      processing and biological activation of not only gastrin but other peptide
      hormones as well.

PMID- 1400489
TI  - Molecular cloning and characterization of a gene encoding pea cytosolic ascorbate
      peroxidase.
AB  - A gene encoding cytosolic ascorbate peroxidase (ApxI) from pea (Pisum sativum L.)
      was isolated and its nucleotide sequence determined. By homologous alignment
      between the ApxI cDNA (Mittler, R., and Zilinskas, B. (1991) FEBS Lett. 289, 257
      259) and the genomic clone, positions of introns and exons were determined. The
      isolated ApxI gene was found to contain 9 introns, the first of which was located
      within the 5'-untranslated region of the mRNA. Southern blot analysis of pea
      genomic DNA suggests that in pea cytosolic ascorbate peroxidase is encoded by a
      single copy gene. Steady state ApxI transcript levels were found to increase in
      response to several stresses imposed by drought, heat, and application of
      ethephon, abscisic acid, and the superoxide-generating agent paraquat. Increases
      in ascorbate peroxidase activity in response to stresses were less marked than
      changes observed in transcript levels; cytosolic ascorbate peroxidase protein
      levels measured by immunoblot analysis remained unchanged.

PMID- 1400490
TI  - Glycosylation and membrane insertion of newly synthesized rat dopamine beta
      hydroxylase in a cell-free system without signal cleavage.
AB  - Dopamine beta-hydroxylase (DBH, EC 1.14.17.1) is present in both membrane-bound
      and soluble forms in neurosecretory vesicles. This study was designed to
      investigate the differences between membrane-bound and soluble DBH and how they
      may arise from translation of a single mRNA. Antisera to a peptide corresponding
      to the carboxyl terminus of rat DBH was found to specifically immunoprecipitate
      the 77- and 73-kDa subunits of newly synthesized DBH in rat brain. Thus, both
      soluble and membrane-bound forms contain the same carboxyl terminus. To
      investigate differences at the amino terminus, full-length rat DBH mRNA,
      translated in a cell-free system, produced a 66-kDa peptide. An additional higher
      molecular mass product was synthesized upon co-translational addition of
      microsomal membranes. This product was glycosylated since it bound to
      concanavalin A-Sepharose and reverted to the 66-kDa polypeptide after treatment
      with endoglycosidase H. This glycosylated product was resistant to protease
      digestion and fractionated with microsomal membranes on sucrose gradients,
      indicating that it is incorporated into the microsomal membranes. Amino-terminal
      sequencing of the glycosylated translation product indicated that the amino
      terminal "signal" sequence was not cleaved. The results indicate that in the cell
      free system newly synthesized DBH undergoes glycosylation and incorporation into
      microsomal membranes without cleavage of the NH2-terminal signal sequence.

PMID- 1400491
TI  - Alpha-thrombin stimulates nuclear diglyceride levels and differential nuclear
      localization of protein kinase C isozymes in IIC9 cells.
AB  - The mechanism by which an agonist, binding to a cell surface receptor, exerts an
      effect on events in the nucleus is not known. We have previously shown (Leach, K.
      L., Ruff, V. A., Wright, T. M., Pessin, M. S., and Raben, D. M. (1991) J. Biol.
      Chem. 266, 3215-3221) that alpha-thrombin treatment of IIC9 cells results in
      increased levels of cellular 1,2-diacylglycerol (DAG) and activation of protein
      kinase C (PKC). Here, we have examined whether changes in nuclear PKC and nuclear
      DAG also are induced following alpha-thrombin treatment. IIC9 cells were treated
      with 500 ng/ml alpha-thrombin, and nuclei were then isolated. Western blot
      analysis using isozyme-specific antibodies demonstrated the presence of PKC
      alpha, but not PKC epsilon or zeta in the nuclei of cells treated with either
      phorbol 12-myristate 13-acetate or alpha-thrombin. The increase in nuclear PKC
      alpha levels was accompanied by a 10-fold increase in nuclear PKC specific
      activity and stimulated phosphorylation of at least six nuclear proteins. The
      rise in nuclear PKC levels occurred rapidly and reached a maximum at 30-60 s,
      which was followed by a decline back to the control level over the next 15 min.
      In addition, alpha-thrombin treatment resulted in an immediate rise in DAG mass
      levels in the nuclear fractions. Kinetic analysis indicated that a maximum
      increase in DAG levels occurred 2.5-5 min after the addition of alpha-thrombin
      and remained elevated for at least 30 min. In cells labeled with [3H]myristic
      acid, alpha-thrombin treatment induced an increase in radiolabeled nuclear
      diglycerides, suggesting that the stimulated nuclear DAGs are derived, at least
      in part, from phosphatidylcholine. Our results suggest that increases in both
      nuclear DAG levels and PKC activity following alpha-thrombin treatment may play a
      role in mediating thrombin-induced nuclear responses such as changes in gene
      expression and cellular proliferation.

PMID- 1400492
TI  - Cloning of cDNA for mosquito lysosomal aspartic protease. Sequence analysis of an
      insect lysosomal enzyme similar to cathepsins D and E.
AB  - A cDNA coding for the lysosomal aspartic protease from the mosquito (mLAP) was
      cloned and sequenced. The mLAP cDNA is 1420 base pairs long with an open reading
      frame of 387 amino acids. The deduced amino acid sequence contains a signal pre
      propeptide sequence of 18 amino acids followed by 369 amino acids with a 35-amino
      acid putative pro-enzyme domain in the NH2-terminal. The amino acid sequence of
      mLAP is 92 and 81% similar to human cathepsin D and cathepsin E, respectively.
      Typical cleavage sites for cathepsin D processing into light and heavy chains are
      lacking in mLAP. A single glycosylation site occurs in the mLAP sequence at a
      position corresponding to the first glycosylation site of cathepsins D. The mLAP
      sequence shares putative phosphorylation determinants, which in cathepsins D are
      linked to the formation of mannose 6-phosphate. In the mosquito fat body,
      lysosomal enzymes specifically degrade organelles involved in the biosynthesis
      and secretion of vitellogenin. The mLAP mRNA accumulates to its highest level 24
      h after initiation of vitellogenin synthesis and 12 h before the peak of mLAP
      protein accumulation and its enzymatic activity. Translational regulation of mLAP
      mRNA may occur. The 5'-untranslated region of mLAP mRNA is similar to elements
      conferring negative translational control by steroids.

PMID- 1400493
TI  - Standardization of mRNA titration using a polymerase chain reaction method
      involving co-amplification with a multispecific internal control.
AB  - We describe a simplified and reliable polymerase chain reaction-based method for
      assaying RNAs of low abundancy. The technique involves the co-amplification of
      cellular RNA-derived cDNA with a multispecific cDNA of synthetic origin added as
      an internal standard, using primer pairs common to both templates. We show that
      the co-amplified templates accumulate in a parallel manner throughout both the
      exponential and nonexponential phases of amplification, even when the starting
      amounts of the templates differ by up to 2 orders of magnitude. This finding
      means that preliminary experiments designed to determine either the late
      exponential region or the amplification efficiency for each pair of primers are
      unnecessary. This has enabled us to develop a greatly simplified quantitation
      protocol. We illustrate our approach by quantifying the effect of the
      immunosuppressor cyclosporin A on the accumulation of interleukin-4, interferon
      gamma, and interleukin-2 receptor mRNAs in phytohemagglutinin-stimulated human
      peripheral blood mononuclear cells.

PMID- 1400494
TI  - Calcium-activated potassium transport and high molecular weight forms of
      calpromotin.
AB  - Investigations of human red blood cells show that a cytoplasmic protein called
      calpromotin is involved in the regulation of calcium-activated potassium
      transport. Calpromotin associates with the membrane in the presence of calcium
      and undergoes a chemical transformation. High performance gel filtration and gel
      electrophoresis show that the cytoplasmic and membrane-bound calpromotin can
      exist in both low and high molecular weight forms. The biochemical properties of
      the high molecular weight membrane-bound calpromotin are not the same as the high
      molecular weight cytoplasmic calpromotin. The high molecular weight membrane
      forms of calpromotin are increased by leupeptin and diminished by iodoacetic
      acid. Therefore, the leupeptin enhancement and iodoacetic inhibition of calcium
      activated potassium transport may involve the high molecular weight forms of
      membrane-bound calpromotin.

PMID- 1400495
TI  - Tyrosine phosphorylation of receptor beta subunits and common substrates in
      response to interleukin-3 and granulocyte-macrophage colony-stimulating factor.
AB  - The receptors for interleukin-3 (IL-3) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) consist of two polypeptides each belonging to a new
      class of molecules referred to as the hemopoietin receptor family. When expressed
      alone, receptor polypeptides of this family often bind their respective factors
      with lower affinity than the receptors identified in whole cells. Despite the
      lack of structural evidence for any enzymatic activity of the receptor
      polypeptides, both IL-3 and GM-CSF stimulate tyrosine phosphorylation of multiple
      intracellular substrates. We investigated IL-3 and GM-CSF receptor structure and
      signaling in a myeloid cell line, FDC-P1, which is dependent on either IL-3 or GM
      CSF for growth. Antiphosphotyrosine antibodies were used to immunoprecipitate
      tyrosine-phosphorylated proteins from 32P-labeled cells or to probe immunoblots.
      Both IL-3 and GM-CSF stimulated the phosphorylation of a similar pattern of
      polypeptides on tyrosine. One tyrosine phosphorylated polypeptide migrated with
      M(r) = 135,000 and increased to 150,000 over a period of 10 min following
      stimulation of cells with IL-3 or GM-CSF. The M(r) = 135,000-150,000 polypeptide
      phosphorylated in response to IL-3 was shown to be primarily the Aic-2A
      polypeptide, the low affinity IL-3 receptor. Phosphatase treatment showed that
      the dramatic IL-3-induced shift in apparent molecular weight from M(r) = 125,000
      in unstimulated cells was entirely due to phosphorylation. The closely related
      receptor, Aic-2B, was also tyrosine phosphorylated in response to IL-3, although
      to a lesser extent than Aic-2A. Treatment with GM-CSF resulted in tyrosine
      phosphorylation of the Aic-2B polypeptide exclusively. It was intriguing that GM
      CSF treatment did affect the mobility of the Aic-2A polypeptide on polyacrylamide
      gels. Together, these results suggest that the Aic-2A polypeptide is part of the
      IL-3 receptor complex, but not the GM-CSF receptor. In contrast, the Aic-2B
      polypeptide is a component of the GM-CSF receptor, but it can also be utilized in
      an IL-3 receptor.

PMID- 1400496
TI  - Effects of site-directed mutagenesis of the highly conserved aspartate residues
      in domain II of farnesyl diphosphate synthase activity.
AB  - Comparison of the farnesyl diphosphate (FPP) synthase amino acid sequences from
      four species with amino acid sequences from the related enzymes hexaprenyl
      diphosphate synthase and geranylgeranyl diphosphate synthase show the presence of
      two aspartate rich highly conserved domains. The aspartate motif ((I, L, or
      V)XDDXXD) of the second of those domains has homology with at least 9 prenyl
      transfer enzymes that utilize an allylic prenyl diphosphate as one substrate. In
      order to investigate the role of this second aspartate-rich domain in rat FPP
      synthase, we mutated the first or third aspartate to glutamate, expressed the
      wild-type and mutant enzymes in Escherichia coli, and purified them to apparent
      homogeneity using a single chromatographic step. Approximately 12 mg of
      homogeneous protein was isolated from 120 mg of crude bacterial extract. The
      kinetic parameters of the purified wild-type recombinant FPP synthase containing
      the DDYLD motif were as follows: Vmax = 0.84 mumol/min/mg; GPP Km = 1.0 microM;
      isopentenyl diphosphate (IPP) Km = 2.7 microM. Substitution of glutamate for the
      first aspartate (EDYLD) decreased the Vmax by over 90-fold. The Km for IPP
      increased, whereas the Km for GPP remained the same in this D243E mutant.
      Substitution of glutamate for the third aspartate (DDYLE) did not result in
      altered enzyme kinetics in the D247E mutant. These results suggest that the first
      aspartate in the second domain is involved in the catalysis by FPP synthase.

PMID- 1400497
TI  - Molecular characterization of a rat negative regulator with a basic helix-loop
      helix structure predominantly expressed in the developing nervous system.
AB  - We report here the cDNA cloning and characterization of a rat basic helix-loop
      helix (HLH) factor, designated HES-5. This factor has a distant sequence homology
      to Drosophila hairy and Enhancer-of-split proteins, both of which are required
      for normal neurogenesis. DNase I footprinting analyses show that HES-5 binds to
      the sequence CACNAG (called N box), a recognition sequence of Enhancer-of-split
      proteins. Although HES-5 does not bind to the sequence CANNTG (called E box)
      recognized by other HLH factors, it attenuates the binding of E47, an HLH
      activator, to E box by forming a hetero-oligomer. In cotransfection analyses
      using NIH 3T3 cells, HES-5 significantly represses transcription originating from
      the promoter containing the N box sequences. Furthermore, HES-5 also partially
      inhibits the E47-induced expression from the promoter containing E boxes.
      Northern blot, RNase protection, and in situ hybridization analyses demonstrate
      that the HES-5 mRNA is specifically expressed in the nervous system. Prominent
      expression is observed in the ventricular zones of the embryonal brain vesicles
      and the outer nuclear layer of the neural retina. These results suggest that the
      negative regulator HES-5 may play an important role in neural development.

PMID- 1400498
TI  - Cell-specific translation of S-adenosylmethionine decarboxylase mRNA. Regulation
      by the 5' transcript leader.
AB  - The mRNA encoding S-adenosylmethionine decarboxylase (AdoMetDC) has an unusual
      distribution in polysomes from cells of T lymphocyte origin. It associates
      predominantly with monosomes and small polysomes with none located in the
      preribosomal or ribonucleoprotein pool. In sharp contrast, it associates broadly
      with larger polysomes in several nonlymphoid cell lines, including fibroblasts
      and the adrenal carcinoma line, Y1. The AdoMetDC 5'-transcript leader (5'-TL) is
      highly conserved between human and bovine mRNAs. It has a length of about 330
      nucleotides and contains a 21-nucleotide upstream open reading frame (uORF)
      approximately 14 nucleotides downstream of the cap site. The AdoMetDC 5'-TL, when
      used to replace the 5'-TL of the human growth hormone gene in a chimeric
      expression construct, causes a suppressed polysomal distribution of the chimeric
      mRNA identical to that of the endogenous AdoMetDC mRNA in the T cell line,
      Jurkat. In contrast, mRNA encoded by the same chimeric construct, when expressed
      in Y1 cells, mimics the broad polysomal distribution of the endogenous AdoMetDC
      mRNA. Mutations that remove the uORF, or prevent its initiation, abolish the
      translational suppression in T cells, establishing that the uORF is a negative
      element that modulates the cell-specific polysomal distribution of AdoMetDC mRNA.

PMID- 1400499
TI  - Distal AP-1 binding sites mediate basal level enhancement and TPA induction of
      the mouse heme oxygenase-1 gene.
AB  - Basal expression of a chimeric gene (pMHO4CAT) consisting of approximately 7
      kilobase pairs (kbp) of the 5'-flanking region of the mouse heme oxygenase-1 (HO
      1) gene fused to the bacterial chloramphenicol acetyltransferase gene is 2- to 10
      fold greater than that of an analogous construct containing only 1287 bp of the
      5'-flanking region (pMHO1CAT) in transiently transfected cultured cells. The
      enhancer activity has been localized to a 268-base pair (bp) fragment positioned
      approximately 4 kilobase pairs upstream of the transcription initiation site.
      This fragment contains two high affinity protein binding sites, regions A and B,
      as determined by DNase I protection assays using nuclear protein extracts from
      rat C6 glioma cells. Both sites include core sequence elements, TGAGTCA (region
      A) and TGTGTCA (region B), that resemble the consensus binding site, TGA(G/C)TCA,
      of the Jun/Fos (AP-1) family of transcription factors. Purified, bacterially
      expressed AP-1 (c-Jun homodimer) specifically binds to both elements, exhibiting
      greater affinity for the region A motif. The expression of pMHO4CAT, but not of
      pMHO1CAT, is stimulated by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate
      (TPA), and the 268-bp enhancer fragment confers TPA inducibility and c-Jun/c-Fos
      transactivation to the heterologous SV40 promoter. These functions are mediated
      by the AP-1 binding sites as multiple copies of the region A motif also confer
      TPA induction and c-Jun/c-Fos transactivation upon a heterologous promoter.

PMID- 1400500
TI  - Ribosome-bound eukaryotic elongation factor 2 protects 5 S rRNA from
      modification.
AB  - The interaction between eukaryotic elongation factor eEF-2 and reconstituted 80 S
      ribosomes was investigated by analyzing the accessibility of 5 S ribosomal RNA
      for chemical and enzymatic modification. Ribosomes reconstituted from derived
      subunits were modified, and the positions of the modified sites were identified
      by primer extension using a 5 S rRNA-specific probe. All reactive sites were
      located between nucleotides 38 and 99, and most of them were found in putative
      single-stranded regions of the 5 S rRNA. Conversion of the ribosomes to the post
      translocation type of particles by treatment with the translational inhibitor
      ricin resulted in the exposure of 3 additional bases for chemical modification,
      suggesting that the 5 S rRNA was more exposed in this type of ribosome. After
      binding of eEF-2 in complex with the non-hydrolyzable GTP analogue guanosine 5'
      (beta, gamma-methylene)-triphosphate, most of the exposed bases in the 5 S rRNA
      were protected against both chemical and enzymatic modification.

PMID- 1400501
TI  - Membrane assembly of the triple-spanning coronavirus M protein. Individual
      transmembrane domains show preferred orientation.
AB  - The M protein of mouse hepatitis virus strain A59 is a triple-spanning membrane
      protein which assembles with an uncleaved internal signal sequence, adopting an
      NexoCcyt orientation. To study the insertion mechanism of this protein, domains
      potentially involved in topogenesis were deleted and the effects analyzed in
      topogenesis were deleted and the effects analyzed in several ways. Mutant
      proteins were synthesized in a cell-free translation system in the presence of
      microsomal membranes, and their integration and topology were determined by
      alkaline extraction and by protease-protection experiments. By expression in COS
      1 and Madin-Darby canine kidney-II cells, the topology of the mutant proteins was
      also analyzed in vivo. Glycosylation was used as a biochemical marker to assess
      the disposition of the NH2 terminus. An indirect immunofluorescence assay on semi
      intact Madin-Darby canine kidney-II cells using domain-specific antibodies served
      to identify the cytoplasmically exposed domains. The results show that each
      membrane-spanning domain acts independently as an insertion and anchor signal and
      adopts an intrinsic preferred orientation in the lipid bilayer which corresponds
      to the disposition of the transmembrane domain in the wild-type assembled
      protein. These observations provide further insight into the mechanism of
      membrane integration of multispanning proteins. A model for the insertion of the
      coronavirus M protein is proposed.

PMID- 1400502
TI  - Cell-free expression of visual arrestin. Truncation mutagenesis identifies
      multiple domains involved in rhodopsin interaction.
AB  - Visual arrestin plays an important role in regulating light responsiveness via
      its ability to specifically bind to the phosphorylated and light-activated form
      of rhodopsin. To further characterize rhodopsin/arrestin interactions we have
      utilized a rabbit reticulocyte lysate translation system to synthesize bovine
      visual arrestin. The translated arrestin (404 amino acids) was demonstrated to be
      fully functional in terms of its ability to specifically recognize and bind to
      phosphorylated light-activated rhodopsin (P-Rh*). Competitive binding studies
      revealed that the in vitro synthesized arrestin and purified bovine visual
      arrestin had comparable affinities for P-Rh*. In an effort to assess the
      functional role of different regions of the arrestin molecule, two truncated
      arrestin mutants were produced by cutting within the open reading frame of the
      bovine arrestin cDNA with selective restriction enzymes. In vitro translation of
      the transcribed truncated mRNAs resulted in the production of arrestins truncated
      from the carboxyl terminus. The ability of each of the mutant arrestins to bind
      to dark (Rh), light-activated (Rh*), dark phosphorylated (P-Rh), and light
      activated phosphorylated rhodopsin were then compared. Arrestin lacking 39
      carboxyl-terminal residues binds specifically not only to P-Rh* but also to Rh*
      and P-Rh. This suggests that the carboxyl-terminal domain of arrestin plays an
      important regulatory role in ensuring strict arrestin binding selectivity to P
      Rh*. Arrestin that has only the first 191 amino-terminal residues predominately
      discriminates the phosphorylation state of the rhodopsin; however, it also
      retains some binding specificity for the activation state. These results suggest
      that the amino-terminal half of arrestin contains key rhodopsin recognition sites
      responsible for interaction with both the phosphorylated and light-activated
      forms of rhodopsin.

PMID- 1400503
TI  - An element regulating adrenal-specific steroid 21-hydroxylase expression is
      located within the slp gene.
AB  - In this report we demonstrate that a transcriptional regulatory element for one
      gene lies within a second, seemingly unrelated gene. Specifically, the 3' portion
      of the murine sex-limited protein (slp) gene, located within the class III region
      of the major histocompatibility complex, contains an element that regulates
      expression of the linked steroid 21-hydroxylase gene. A 4.2-kilobase (kb) major
      histocompatibility complex region, located between -2.2 and -6.4 kb upstream of
      21OH-A, is required for expression of a chloramphenicol acetyltransferase
      reporter gene in transgenic mice. Two short regions of DNA, located between -5.3
      and -6.0 kb, stimulate chloramphenicol acetyltransferase expression in Y1
      adrenocortical tumor cells, and both of these active regions lie within the slp
      gene. A 21-base pair sequence, which is required for activity of the most 3'
      region, does not contain any of over 100 previously identified transcriptional
      regulatory elements. This juxtaposition of structural and regulatory elements of
      otherwise unrelated genes suggests a mechanism by which the evolutionarily
      conserved genetic linkage of 21OH-A and slp (or the homologous complement
      component C4) might provide a selective advantage. Analogous genetic arrangements
      may explain other examples of conserved linkage of disparate genes.

PMID- 1400504
TI  - Role of tryptophan 49 in the heparin cofactor activity of human antithrombin III.
AB  - To probe the functional role of tryptophan 49 in human antithrombin III, a mutant
      antithrombin, W49K, has been expressed in baby hamster kidney cells. The mutation
      reduces the affinity for heparin pentasaccharide by 1.8 kcal mol-1 but does not
      alter the heparin enhancement of the rate of factor Xa inhibition. 1H NMR spectra
      of W49K antithrombin show that the structure of the protein and the mode of
      heparin binding appear to be unaltered by the mutation, although tryptophan 49 is
      perturbed by heparin binding. 19F NMR spectra of 6-fluorotryptophan-substituted
      antithrombin show that tryptophan 49 is in a solvent-exposed environment. The
      heparin-induced fluorescence enhancement of W49K antithrombin is significantly
      different from that of wild-type antithrombin. Pentasaccharide induces only a 24%
      enhancement of antithrombin fluorescence, while high affinity heparin induces an
      enhancement of 40%. The results indicate that tryptophan 49 is probably a heparin
      contact residue but can be mutated without altering the remaining heparin
      antithrombin interactions or the heparin-induced conformational change and
      resultant activation toward Factor Xa. Hydrophobic as well as charge interactions
      are thus probably involved in the specificity of the antithrombin-heparin
      pentasaccharide interaction. The lower fluorescence enhancements suggest that the
      heparin-induced 40% fluorescence enhancement used as the hallmark of activating
      heparin species is not the best indicator of the structural change in
      antithrombin that results in enhancement of the rate of proteinase inhibition.

PMID- 1400505
TI  - Mammalian nitrobenzylthioinosine-sensitive nucleoside transport proteins.
      Immunological evidence that transporters differing in size and inhibitor
      specificity share sequence homology.
AB  - Polyclonal antibodies were raised against the nitrobenzylthioinosine (NBMPR)
      sensitive nucleoside transporter of human erythrocyte membranes. On Western blots
      of these membranes they labeled the broad "band 4.5" region (average apparent
      M(r) 55,000), which contains both the nucleoside and glucose transport proteins.
      However, they did not recognize the glucose transporter when this was prepared
      free of nucleoside transporter by expression from a cDNA clone. Their specificity
      for the nucleoside transporter was confirmed by the ability to immunoadsorb NBMPR
      but not cytochalasin B-binding sites from a detergent-solubilized mixture of
      band 4.5 proteins. Although a large proportion of the antibodies recognized
      extracellular epitopes, these appeared to be located primarily on the polypeptide
      moiety of the glycoprotein, as demonstrated by the ability of the antibodies
      strongly to label the deglycosylated transporter (apparent M(r) 45,000) on
      Western blots. The antibodies were species-cross-reactive, recognizing nucleoside
      transporters from pig and rabbit erythrocytes and from rat liver. The pig protein
      is similar to the human transporter in its inhibitor sensitivity but is
      considerably larger (apparent M(r) 57,000 after deglycosylation). In contrast,
      the rat protein is similar in size to the human transporter (apparent M(r) 45,000
      after deglycosylation) but much less sensitive to the inhibitors dilazep and
      dipyridamole. These findings indicate that despite their differences in size and
      inhibitor specificity, the NBMPR-sensitive nucleoside transporters of these
      mammalian species are related in amino acid sequence.

PMID- 1400506
TI  - Human plasma lipoproteins regulate apolipoprotein E secretion from a post-Golgi
      compartment.
AB  - The molecular regulation of apolipoprotein E (apoE) synthesis and secretion is
      incompletely understood. In this study, we have examined the effect of human low
      density lipoprotein (LDL) on apoE mRNA and protein levels in HepG2 and other
      eukaryotic cells. Exposing HepG2 cells to LDL for times up to 4 h resulted in an
      increase in 35S-labeled apoE accumulation in the medium by 2.2-fold, relative to
      serum free controls (n = 10, p < 0.001), with no changes in apoE mRNA levels.
      Similar observations have been made in JeG-3 cells and Chinese hamster ovary
      cells stably transfected with human apoE cDNA constructs. These results indicate
      that the LDL effect operates at a post-transcriptional level. In pulse-chase
      experiments, the LDL effect on apoE accumulation in the media was observed when
      it was added only during the chase even in the presence of cycloheximide,
      indicating that LDL is functioning at a post-translational level. The use of
      brefeldin A (BFA), an agent that impedes protein transport from the endoplasmic
      reticulum to the Golgi apparatus, suggests that the LDL effect occurs in a post
      Golgi compartment. The addition of protease inhibitors could not duplicate the
      effects of LDL on the apoE accumulation in the medium. ApoA-I accumulation in the
      medium of HepG2 cells, but not albumin, was also significantly increased by 1.9
      fold (n = 5, p < 0.001).

PMID- 1400507
TI  - Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the
      key enzyme for L-ascorbic acid biosynthesis missing in this species.
AB  - Guinea pigs cannot synthesize L-ascorbic acid because of their deficiency in L
      gulono-gamma-lactone oxidase, a key enzyme for the biosynthesis of this vitamin
      in higher animals. In this study we isolated the L-gulono-gamma-lactone oxidase
      gene of the rat and the homologue of this gene of the guinea pig by screening rat
      and guinea pig genomic DNA libraries in lambda phage vectors, respectively, using
      a rat L-gulono-gamma-lactone oxidase cDNA as a probe. Sequencing analysis showed
      that the amino acid sequence of the rat enzyme is encoded by 12 exons and that
      all the intron/exon boundaries follow the GT/AG rule. On the other hand, regions
      corresponding to exons I and V were not identified in the guinea pig L-gulono
      gamma-lactone oxidase gene homologue. Other defects found in this gene homologue
      are a deletion of the nucleotide sequence corresponding to a 3' 84-base pair part
      of rat exon VI, a 2-base pair deletion in the remaining exon VI-related region,
      and nonconformance to the GT/AG rule at one of the putative intron/exon
      boundaries. Furthermore, a large number of mutations were found in the amino acid
      coding regions of the guinea pig sequence; more than half of them lead to
      nonconservative amino acid changes, and there are three stop codons as well. Thus
      it is clear that the guinea pig homologue of the L-gulono-gamma-lactone oxidase
      gene exists as a pseudogene that randomly accumulated a large number of mutations
      without functional constraint since the gene ceased to be active during
      evolution. On the basis of the neutral theory of evolution, the date of the loss
      of L-gulono-gamma-lactone oxidase in the ancestors of the guinea pig was roughly
      calculated to be less than 20 million years ago.

PMID- 1400508
TI  - A missense mutation of L-gulono-gamma-lactone oxidase causes the inability of
      scurvy-prone osteogenic disorder rats to synthesize L-ascorbic acid.
AB  - The osteogenic disorder Shionogi (ODS) rat is a mutant Wistar rat that is subject
      to scurvy, because it lacks L-gulono-gamma-lactone oxidase, a key enzyme in L
      ascorbic acid biosynthesis. Sequencing of polymerase chain reaction-amplified
      cDNAs for mutant and normal rat L-gulono-gamma-lactone oxidases demonstrated that
      the mutant cDNA has a single base mutation from G to A at nucleotide 182, which
      mutation alters the 61st amino acid residue from Cys to Tyr. To test the effect
      of this mutation on the expression of L-gulono-gamma-lactone oxidase, we inserted
      a region of the cDNAs coding for normal and mutant L-gulono-gamma-lactone
      oxidases into an expression vector, pSVL, and transfected COS-1 cells with such
      vectors. The result indicated that the defined amino acid substitution does
      decrease both the amount of immunologically detectable protein and the level of
      enzyme activity to about one-tenth of their normal values, while it does not
      affect the amount of the mRNA produced in the transfected cells. This situation
      is similar to our previous observation that L-gulono-gamma-lactone oxidase is
      expressed in the liver of the ODS rat at a very low level irrespective of the
      presence of a normal amount of L-gulono-gamma-lactone oxidase-specific mRNA of a
      normal size (Nishikimi, M., Koshizaka, T., Kondo, K., and Yagi, K. (1989)
      Experientia (Basel) 45, 126-129). Thus it became clear that the Cys-->Tyr
      substitution is responsible for the L-gulono-gamma-lactone oxidase deficiency in
      the ODS rat.

PMID- 1400509
TI  - Phosphorylation of the Rex protein of human T-cell leukemia virus type I.
AB  - Rex protein, the posttranscriptional regulator of human T-cell leukemia virus
      type I (HTLV-I), is required for the control of viral structural protein
      expression and virus replication. Rex is a phosphoprotein found predominantly in
      the cell nucleolus, whose function is thought to be regulated by its nucleolar
      localization and phosphorylation. Therefore, we investigated the in vivo
      phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in
      all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and
      to a very small extent at threonine residues. Treatment of cells with 12-O
      tetradecanoylphorbol-13-acetate (TPA) led to significant but transient
      enhancement of the incorporation of [32P]orthophosphate into Rex protein. N
      terminal truncation of Rex protein abolished TPA-dependent phosphorylation.
      Chymotryptic digestion of phosphorylated Rex yielded two phosphopeptides. In vivo
      phosphorylation sites were identified as serine residues 70 and 177 and threonine
      residue 174. Serine 70 was a TPA-dependent phosphorylation site within a
      regulatory domain. We have already shown that the protein kinase C inhibitor H-7
      (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) specifically blocked
      accumulation of viral unspliced gag-pol mRNA. Therefore, the phosphorylation at
      serine 70 may be involved in the regulation of Rex function in response to
      extracellular stimuli.

PMID- 1400510
TI  - Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily.
AB  - Angiogenin is a 14.4-kDa human plasma protein with 65% homology to RNase A that
      retains the key active site residues and three of the four RNase A disulfide
      bonds. We demonstrate that recombinant angiogenin functions as a cytotoxic tRNA
      specific RNase in cell-free lysates and when injected into Xenopus oocytes.
      Inhibition of protein synthesis by angiogenin correlates with degradation of
      endogenous oocyte tRNA. Exogenous, radiolabeled tRNA is also hydrolyzed by
      angiogenin, whereas oocyte rRNA and mRNA are not detectably degraded by
      angiogenin. Protein synthesis was restored to angiogenin-injected oocytes by
      injecting the RNase inhibitor RNasin plus total Xenopus or calf liver tRNAs,
      thereby demonstrating that the tRNA degradation induced by angiogenin was the
      sole cause of cytotoxicity. A similar tRNA-reversible inhibition of protein
      synthesis was seen in rabbit reticulocyte lysates. Angiogenin therefore appears
      to be a specific cellular tRNase, whereas five homologues in the RNase A
      superfamily lack angiogenin's specificity for tRNA. One of these homologues
      purified from human eosinophils, eosinophil-derived neurotoxin, nonspecifically
      degrades oocyte RNA similar to RNase A and is also cytotoxic at very low
      concentrations.

PMID- 1400511
TI  - A fluid-structure interaction problem in biomechanics: prestressed vibrations of
      the eye by the finite element method.
AB  - The object of this work has been to develop a mechanical and numerical model of
      the eye submitted to vibrations, and in particular, to calculate the influence of
      intraocular pressure (IOP) on the eye resonance frequencies. Our mechanical model
      of the eye relies upon the theory of the mechanics of continuous media. The
      numerical model results from a model analysis of the vibrations of the eye using
      a finite element method (FEM) for discretization. The eye can be schematically
      represented as a prestressed shell, filled by an inviscid barotropic compressible
      fluid, which leads us to formulate and solve a problem of vibrations of a coupled
      fluid-structure system. The corneoscleral shell has been modeled as a thin and
      thick shell, taking into account material nonlinearities in the thick case.
      Numerical results obtained for the attached eye demonstrate a fair sensitivity of
      the resonance frequencies to the variations of the IOP; thus, founding the
      interest of the surveillance of the resonance frequency of the eye.

PMID- 1400512
TI  - Description of the deformation of the left ventricle by a kinematic model.
AB  - A model of left ventricular (LV) kinematics is essential to identify the
      fundamental physiological modes of LV deformation during a complete cardiac cycle
      as observed from the motion of a finite number of markers embedded in the LV
      wall. Kinematics can be described by a number of modes of motion and deformation
      in succession. An obvious mode of LV deformation is the ejection of cavity volume
      while the wall thickens. In the more sophisticated model of LV kinematics
      developed here, seven time-dependent parameters were used to describe not only
      volume change but also torsion and shape changes throughout the cardiac cycle.
      Rigid-body motion required another six parameters. The kinematic model employed a
      deformation field that had no singularities within the myocardium, and all
      parameters describing the modes of deformation were dimensionless. Note that
      torsion, volume and symmetric shape changes all require the definition of a
      cardiac coordinate system, which has generally been related to the measured
      cardiac geometry by reference to approximate anatomical landmarks. However, in
      the present study the coordinate system was positioned objectively by a least
      squares fit of the kinematic model to the measured motion of markers.
      Theoretically, at least five markers are needed to find a unique set of
      parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400513
TI  - Dependence of local left ventricular wall mechanics on myocardial fiber
      orientation: a model study.
AB  - The dependence of local left ventricular (LV) mechanics on myocardial muscle
      fiber orientation was investigated using a finite element model. In the model we
      have considered anisotropy of the active and passive components of myocardial
      tissue, dependence of active stress on time, strain and strain rate, activation
      sequence of the LV wall and aortic afterload. Muscle fiber orientation in the LV
      wall is quantified by the helix fiber angle, defined as the angle between the
      muscle fiber direction and the local circumferential direction. In a first
      simulation, a transmural variation of the helix fiber angle from +60 degrees at
      the endocardium through 0 degrees in the midwall layers to -60 degrees at the
      epicardium was assumed. In this simulation, at the equatorial level maximum
      active muscle fiber stress was found to vary from about 110 kPa in the
      subendocardial layers through about 30 kPa in the midwall layers to about 40 kPa
      in the subepicardial layers. Next, in a series of simulations, muscle fiber
      orientation was iteratively adapted until the spatial distribution of active
      muscle fiber stress was fairly homogeneous. Using a transmural course of the
      helix fiber angle of +60 degrees at the endocardium, +15 degrees in the midwall
      layers and -60 degrees at the epicardium, at the equatorial level maximum active
      muscle fiber stress varied from 52 kPa to 55 kPa, indicating a remarkable
      reduction of the stress range. Moreover, the change of muscle fiber strain with
      time was more similar in different parts of the LV wall than in the first
      simulation. It is concluded that (1) the distribution of active muscle fiber
      stress and muscle fiber strain across the LV wall is very sensitive to the
      transmural distribution of the helix fiber angle and (2) a physiological
      transmural distribution of the helix fiber angle can be found, at which active
      muscle fiber stress and muscle fiber strain are distributed approximately
      homogeneously across the LV wall.

PMID- 1400514
TI  - Finite element simulation of pulsatile flow through arterial stenosis.
AB  - The problem of blood flow through a stenosis is solved using the incompressible
      Navier-Stokes equations in a rigid circular tube presenting a partial occlusion.
      Calculations are based on a Galerkin finite element method. The time marching
      scheme employs a predictor-corrector technique using a variable time step.
      Results are obtained for steady and physiological pulsatile flows. Computational
      experiments analyse the effect of varying the degree of stenosis, the stricture
      length, the Reynolds number and Womersley number. The method gives results which
      agree well with previous computations for steady flows and experimental findings
      for steady and pulsatile flows.

PMID- 1400515
TI  - Three-dimensional geometrical and mechanical modelling of the lumbar spine.
AB  - The main objective of this study is to design a three-dimensional geometrical and
      mechanical finite element model of the lumbar spine. The model's geometry is
      constructed using six parameters per vertebra. These parameters are digitized
      from two X-rays (anterio-posterior and lateral), thus yielding an individualized
      model which can be arrived at from the radiographs of a tested specimen. This
      procedure makes the model validation easier, as geometry is generally a factor of
      dispersion in experimental results. The geometrical reconstruction, in the form
      of a finite elements mesh, was effected for the whole lumbar spine. The global
      coherence of the model was verified.

PMID- 1400516
TI  - The onset and progression of spinal injury: a demonstration of neutral zone
      sensitivity.
AB  - Spinal injuries are a great cost to society and the afflicted individuals. It is
      well known that most spinal injuries are not bony fractures but rather soft
      tissue lesions falling in the 'subfailure' region. For the clinical diagnosis of
      spinal injuries, abnormal motion patterns under physiological loads are
      considered an important factor. The purpose of the present study was to determine
      the onset and progression of spinal injury, and compare the sensitivity of three
      motion parameters: neutral zone (NZ), elastic zone (EZ), and range of motion
      (ROM). Spinal injury was defined as a significant increase in any of the three
      motion parameters. A repeatable high-speed flexion-compression load vector was
      applied individually to six porcine cervical spine specimens. Several impacts of
      increasing severity were applied to each specimen. After each impact, flexion
      extension motion was measured. Neutral zone was the residual deformation from the
      neutral position to the position under zero load at the start of the final load
      cycle. Elastic zone was the displacement from zero load to the maximum load on
      the final load cycle. Range of motion was the sum of the neutral and elastic
      zones. The first significant increase in motion was determined by the neutral
      zone parameter with few observable anatomic lesions on the specimens. This was
      the onset of spinal injury. The next significant motion increase was also
      determined by the neutral zone parameter. After this motion increase, termed the
      progression of injury, ligament ruptures were observed in some specimens. It was
      concluded that the neutral zone was the most sensitive motion parameter in
      defining the onset and progression of spinal injury.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1400517
TI  - Effects of changes in segmental values and timing of both torque and torque
      reversal in simulated throws.
AB  - An overarm throw in the sagittal plane was simulated using a three-segment model
      representing the upper arm, forearm and hand plus ball. Torque inputs at each
      joint were turned on at systematically varied times and maintained constant once
      initiated. All simulations began from identical initial conditions. The aim was
      to determine the sequence of onset of joint torques which gave the maximal range
      which the ball would travel and the maximal velocity of the ball irrespective of
      direction. Best throws proved to be sequential in that joint torques were turned
      on in a proximal to distal (P-D) temporal sequence. The P-D sequence was also
      demonstrated by time of peak joint angular velocities. The P-D sequence also
      proved to be best when segmental constants and joint torques were changed. As
      this sequence is a common feature of skilled throwing and striking, it is
      concluded that the linked segmental nature of the limb, irrespective of normal
      muscle characteristics, primarily predisposes the system to the use of a P-D
      sequence. The algebraic sign of the shoulder and elbow torques was reversed
      instantaneously to represent the use of antagonistic muscles. This led to
      increased output if performed late in the throw and in a P-D sequence. It is
      concluded that the use of antagonism leads to beneficial redistributions of
      angular velocity amongst limb segments.

PMID- 1400518
TI  - Mechanical properties of the human lumbar anterior longitudinal ligament.
AB  - A new technique incorporating a motion analysis system and a materials testing
      machine was used to investigate regional differences in the tensile mechanical
      properties of the lumbar spine anterior longitudinal ligament (ALL). Bone-ALL
      bone specimens were prepared from young human cadaveric motion segments with no
      disc or bony pathology. Each specimen was distracted until failure at a constant
      crosshead displacement rate of 2.5 mm s-1 (approximately 1.0% strain per second).
      Strains were evaluated from digitized video recordings of markers attached to the
      ALL at 12 sites along its length and width, including the ligament substance and
      insertions. The 'overall' strain in the ligament was calculated from the
      outermost pairs of markers along the ligament length. The average tensile
      strength, the 'overall' tensile modulus and the 'overall' strain of the ALL at
      failure were 27.4 MPa (S.D. 5.9), 759 MPa (S.D. 336) and 4.95% (S.D. 1.51),
      respectively. Large and significant variations in the strains were present along
      the width and length of the ALL. Peak substance strains were over twofold greater
      than peak strains at the ligament insertion sites, whereas across the ligament
      width, peak strains in the outer portion of the ligament were over 40% greater
      than in the central region. Failure consistently occurred in the ligament mid
      substance and ultimate strains at the ligament failure site averaged 12.1% (S.D.
      2.3). These results indicate that the strains are highly nonuniform in the normal
      ALL.

PMID- 1400519
TI  - The effect of lower-limb anatomy on knee loads during seated cycling.
AB  - Overuse knee joint injuries are the primary injuries to cyclists. Overuse
      injuries have been intuitively linked to the anatomic structure of the foot
      because external loads are applied to the foot in cycling. Thus, the structure
      and function of the foot should dictate in part how the loads are transmitted to
      the knee joint. Therefore, it was hypothesized that patterns in knee loads are
      related to the anatomic structure of the foot. To test this hypothesis, peak knee
      loads (dependent variables) were related to anatomical variables (independent
      variables) through statistical analyses. This required first the detailed
      evaluation (i.e. measurement) of the anatomical structure of the foot and leg for
      23 subjects. Next, three-dimensional knee joint loads were determined for a
      standardized riding condition. The results of the statistical analyses indicated
      that a group of cyclists with the most extreme inversion of the forefoot relative
      to the transverse plane developed significantly greater average posterior knee
      force and extensive knee moment. In addition, a number of anatomical variables
      significantly accounted for the variability in peak values of the posterior
      force, the extensive moment, the varus/valgus moment and the external axial
      moment. Based on these results, the hypothesis is accepted.

PMID- 1400520
TI  - An explicit expression for the moment in multibody systems.
AB  - The equations of motion are formulated for a set of interacting rigid bodies. An
      explicit formulation could be derived for the total moment of the forces on such
      a system. This is applied to (1) the intersegmental moment in a multisegment
      rigid-body model, and (2) the interpretation of the 'centre of pressure' as
      defined in the studies of human posture.

PMID- 1400521
TI  - Mechanical pulse wave propagation in gel, normal and oedematous tissues.
AB  - The velocity, attenuation and frequency content of the mechanical pulse wave
      propagation in gels of various water contents, in normal tissues from various
      sites and in oedematous tissues from different patients were investigated. The
      properties of the propagated pulse wave depend on the water content of the gel
      and the viscoelastic properties of the tissues. From the dependence of the pulse
      wave propagation velocity on elasticity, viscosity and density, information may
      be obtained concerning the effects of oedema on the mechanical properties of
      tissue.

PMID- 1400522
TI  - SPACAR: a software subroutine package for simulation of the behavior of
      biomechanical systems.
AB  - Direct dynamics computer simulation is gaining importance as a research tool in
      the biomechanical study of complex human movements. Therefore, the need for
      general-purpose software packages with which the equations of motion can be
      derived automatically and solved numerically is growing. In this paper such a
      method is described: SPACAR. The method is compared to well-known commercially
      available software packages. On the basis of the results obtained on a test
      problem simulated with both SPACAR and DADS, it is concluded that both methods
      are accurate; DADS is much faster. The user-friendliness of SPACAR is less than
      that of DADS. However, SPACAR has two major advantages. First is the basic
      deformability of all elements, which allows handling of all kinds of problems
      within a unified framework; second is the full availability of the source code,
      which allows the experienced user to broaden the scope of possibilities to any
      extent.

PMID- 1400523
TI  - Calibration characteristics of a video dimension analyser (VDA) system.
AB  - A comprehensive calibration and error analysis of a video dimension analyser
      (VDA) system was carried out to determine the effects of various parameters
      relevant to actual test conditions on the characteristics of the system. The
      parameters considered were: (1) varying distances or angles between the test
      specimen and the camera; (2) refractive effects of glass tank and physiologic
      solutions; and (3) dynamic response of the VDA system. The error analysis shows
      that, at low strain levels, the strain computed by the VDA is sensitive to camera
      placement and orientation as well as the media through which the object is
      observed. Very large errors can occur at small nominal strains, depending on the
      system parameters (e.g. 80% error at 1% nominal strain for one set of
      parameters). At higher strain levels, the sensitivity of the system is reduced,
      and the strain computed by the VDA system approaches the nominal strain (10%
      error at 10% nominal strain).

PMID- 1400524
TI  - Ground reaction forces during termination of human gait.
AB  - This is the first published report of the ground reaction forces during gait
      termination. Two mechanisms appear to be used to stop walking: increased braking
      forces and decreased push-off force. There appears to be a short interval of time
      during the gait cycle in which a decision to take an additional step is to be
      made.

PMID- 1400525
TI  - Step length and frequency effects on ground reaction forces during walking.
AB  - It is well established that the speed of walking or running significantly affects
      ground reaction force (GRF) characteristics. While it is sometimes assumed that
      the variations in step length (SL) and step frequency (SF) also affect GRF
      patterns, little documentation of this can be found in the literature. Ten young
      adults performed overground walking at 1.43 m s-1 across a force platform under
      five SL conditions: preferred SL and SLs that were longer and shorter than the
      preferred by 5 and 10% of greater trochanter height. The contact time,
      anteroposterior braking and propulsive force and impulse descriptors, and
      vertical impulse per step increased systematically as SL increased. In contrast,
      vertical peak forces and impulse per meter walked showed little change with SL
      manipulation. Despite the systematic effect of SL on several GRF descriptors,
      constraint of SL and SF in gait assessments is not recommended as this would
      prohibit the evaluation of representative gait kinematics and kinetics. Rather,
      these results suggest that researchers should report SL and SF data when
      comparing GRF characteristics between experimental groups or conditions, and
      should be alert to the association between SL/SF and GRF's when interpreting GRF
      trends.

PMID- 1400526
TI  - Characterization of in vivo strain in the rat tibia during external application
      of a four-point bending load.
AB  - This paper describes a technique for characterizing strains and stresses induced
      in vivo in the rat tibia during application of an external four-point bending
      load. An external load was applied through the muscle and soft tissue with a four
      point bending device, to induce strain in a 11 mm section of the right tibiae of
      ten adult female Sprague-Dawley rats. Induced strains were measured in vivo on
      the lateral surface of the tibia. Inter-rat difference, leg positioning and
      strain gage placement were evaluated as sources of variability of applied
      strains. Beam bending theory was used to predict externally induced in vivo
      strains. Finite element analysis was used to quantify the magnitude of shear
      stresses induced by this type of loading. There was a linear relationship between
      applied load and induced in vivo strains. In vivo strains induced by external
      loading were linearly correlated (R2 = 0.87) with the strains calculated using
      beam bending theory. The finite element analysis predicted shear stresses at less
      than 10% of the longitudinal stresses resulting from four-point bending. Strains
      predicted along the tibia by finite element analysis and beam bending theory were
      well-correlated. Inter-rat variability due to tibia size and shape difference was
      the most important source of variation in induced strain (CV = 21.6%). Leg
      positioning was less important (CV = 9.5%).

PMID- 1400527
TI  - Comments on 'Thoracic injury potential of basic competition Taekwondo kicks'.

PMID- 1400528
TI  - Biomechanics of the finger with anatomical restrictions--the significance for the
      exercising hand of the musician.
AB  - Exercise and teaching of musicians presupposes in the individual the constitutive
      ability to freely execute the finger movements required in the playing of the
      instrument. However, in the hand anatomical restrictions may exist that limit the
      mobility of the fingers and, thereby, the possibility to determine their
      movements voluntarily. In this article we investigate the kinematics of a
      monodigital system in which restrictions are present.

PMID- 1400529
TI  - Coordination of the leg muscles in backlift and leglift.
AB  - Net joint moments are often used to quantify the loading of structures (e.g. the
      intervertebral disc at L5S1) during lifting. This quantification method is also
      used to evaluate the loading of the knee, for instance, to determine the effect
      of backlifting as opposed to leglifting. However, the true loading of the joint
      as derived from net joint moments can be obscured by a possible co-contraction of
      antagonists. To unravel the mechanisms that determine the net joint moments in
      the knee, the leglift was compared to the backlift. Although a completely
      different net knee moment curve was found when comparing the two lifting
      techniques, it appeared to be closely related to the ground reaction force vector
      and its orientation with respect to the joint centre of rotation (R > 0.995).
      This close relation was established by co-contraction of both flexors and
      extensors of the knee. Furthermore, a close relation appeared to exist between
      the joint moment difference between hip and knee and the activity difference
      between rectus femoris muscle and hamstring (R = 0.72 and 0.83 in leglift and
      backlift, respectively). The knee-ankle joint moment difference and the activity
      of the gastrocnemius showed a close relation as well (R = -0.89 and 0.96 in
      leglift and backlift, respectively). These relations can be interpreted as a
      mechanism to distribute net moments across joints. It is concluded that during
      lifting tasks the intermuscular coordination is aimed at coupling of joint
      moments, such that the ground reaction force points in a direction that provides
      balance during the movement. The use of net joint moments as direct indicators
      for joint loading (e.g. knee) seems, therefore, questionable.

PMID- 1400530
TI  - A kinematic and strain gauge study of the reciprocal apparatus in the equine hind
      limb.
AB  - Hind limb kinematics were recorded in five horses at walk and trot using an opto
      electronic CODA-3 system. Simultaneously, in vivo strain in the completely
      tendinous peroneus tertius muscle was registered by implanted mercury-in-silastic
      strain gauges. The origin-insertion length patterns of the peroneus tertius were
      calculated from raw kinematic data and from data corrected for the error caused
      by skin displacement, and compared with the directly measured strain. The strain
      patterns calculated from externally measured kinematic data appeared to be in
      accordance with the directly measured strain gauge data. However, a correction
      for skin displacement is an obligatory prerequisite to obtain reliable results.
      The amplitudes of strain did not exceed 3% and appeared to be of about the same
      magnitude at both walk and trot.

PMID- 1400531
TI  - Relation between diameter and flow in major branches of the arch of the aorta.
AB  - In the analysis of arterial branching the classical "cube law' has provided a
      working model for the relation between the diameter of a blood vessel and the
      flow which the vessel carries on a long-term basis. The law has shown good
      agreement with biological data, but questions remain regarding its applicability
      to all levels of the arterial tree. The present study tests the hypothesis that
      the cube law may not be valid in the first few generations of the arterial tree,
      where vessel capacitance and gross anatomy may play important roles. Biological
      data have shown some support for this hypothesis in the past but the
      heterogeneity characteristic of past data has not allowed a conclusive test so
      far. We present new data which have been obtained from the same location on the
      arterial tree and in sufficient number to make this test possible for the first
      time. Also, while past tests have been based primarily on correlation of the
      measured data with an assumed power law, we show here that this can be
      misleading. The present data allow a simpler test which does not involve
      correlation and which leads to more direct conclusions. For the vessels surveyed,
      the results show unequivocally that the relation between diameter and flow is
      governed by a 'square law' rather than the classical cube law. Coupled with past
      findings this suggests that the square law may apply at the first few levels of
      the arterial tree, while the cube law continues from there to perhaps the
      precapillary levels.

PMID- 1400532
TI  - On the relationship between the microstructure of bone and its mechanical
      stiffness.
AB  - A recent study of bone structure shows that the plate-shaped carbonate apatite
      crystals in individual lamellae are arranged in layers across the lamellae, and
      that the orientation of these layers are different in alternate lamellae. Based
      on these findings, a new micromechanical model for the Young's modulus of bone is
      proposed, which accounts for the anisotropy and geometrical characteristics of
      the material. The model incorporates the platelet-like geometry of the basic
      reinforcing unit, the presence of alternating thin and thick lamellae, and the
      orientations of the crystal platelets in the lamellae. The thin and thick
      lamellae are modeled as orthotropic composite layers made up of thin rectangular
      apatite platelets within a collagen matrix, and classical orthotropic elasticity
      theory is used to calculate the Young's modulus of the lamellae. Bone is viewed
      as an assembly of such orthotropic lamellae bent into cylindrical structures, and
      having a constant, alternating angle between successive lamellae. The
      micromechanical model employs a modified rule-of-mixtures to account for the two
      types of lamellae. The model provides a curve similar to the published
      experimental data on the angular dependence of Young's modulus, including a local
      maximum at an angle between 0 and 90 degrees. A rigorous testing of the model
      awaits additional experimental data.

PMID- 1400533
TI  - Changes in the microstructure of cultured porcine aortic endothelial cells in the
      early stage after applying a fluid-imposed shear stress.
AB  - Time course changes in the cell shape and in the patterns of microfilament
      distribution were analyzed quantitatively using cultured porcine aortic
      endothelial cell monolayers before and after a shear flow exposure. Geometrical
      parameters of the cell and of the microfilament were measured on fluorescent
      photomicrographs of the cells stained with rhodamine-phalloidin. After the shear
      flow exposure (20 dyn cm-2, 0-24 h), the endothelial cells on glass were
      elongated and oriented to the direction of the flow. Under the no-flow condition,
      F-actin filaments were mainly localized at the periphery of the cell, although
      some filaments were seen in the more central portion. The angles of the filaments
      were randomly distributed. After 3 h, the stress fiber-like structure of an F
      actin bundle was formed in the central part of the cells, and these filaments
      were oriented to the direction of the flow. The degree of orientation increased
      as the time of exposure to shear stress became longer. This change in F-actin
      preceded cell elongation and orientation; these changes were statistically
      significant only after 6 h. After 24 h, peripheral filaments were again observed,
      and the fluorescence intensity of rhodamine-phalloidin-stained cells was
      enhanced. These findings suggest that the redistribution of F-actin filaments is
      one of the early cellular responses to the onset of shear stress and that it is
      one of the most important factors controlling cell elongation and orientation to
      the direction of the flow.

PMID- 1400534
TI  - Force-length properties and functional demands of cat gastrocnemius, soleus and
      plantaris muscles.
AB  - The purpose of this study was to measure isometric force-length properties of cat
      soleus, gastrocnemius and plantaris muscle-tendon units, and to relate these
      properties to the functional demands of these muscles during everyday locomotor
      activities. Isometric force-length properties were determined using an in situ
      preparation, where forces were measured using buckle-type tendon transducers, and
      muscle-tendon unit lengths were quantified through ankle and knee joint
      configurations. Functional demands of the muscles were assessed using direct
      muscle force measurements in freely moving animals. Force-length properties and
      functional demands were determined for soleus, gastrocnemius and plantaris
      muscles simultaneously in each animal. The results suggest that isometric force
      length properties of cat soleus, gastrocnemius and plantaris muscles, as well as
      the region of the force-length relation that is used during everyday locomotor
      tasks, match the functional demands.

PMID- 1400535
TI  - Theoretical analysis of pressure pulse propagation in arterial vessels.
AB  - An original mathematical model of viscous fluid motion in a tapered and
      distensible tube is presented. The model equations are deduced by assuming a two
      dimensional flow and taking into account the nonlinear terms in the fluid motion
      equations, as well as the nonlinear deformation of the tube wall. One distinctive
      feature of the model is the formal integration with respect to the radial
      coordinate of the Navier-Stokes equations by power series expansion. The
      consequent computational frame allows an easy, accurate evaluation of the effects
      produced by changing the values of all physical and geometrical tube parameters.
      The model is employed to study the propagation along an arterial vessel of a
      pressure pulse produced by a single flow pulse applied at the proximal vessel
      extremity. In particular, the effects of the natural taper angle of the arterial
      wall on pulse propagation are investigated. The simulation results show that
      tapering considerably influences wave attenuation but not wave velocity. The
      substantially different behavior of pulse propagation, depending upon whether it
      travels towards the distal extremity or in the opposite direction, is observed:
      natural tapering causes a continuous increase in the pulse amplitude as it moves
      towards the distal extremity; on the contrary, the reflected pulse, running in
      the opposite direction, is greatly damped. For a vessel with physical and
      geometrical properties similar to those of a canine femoral artery and 0.1 degree
      taper angle, the forward amplification is about 0.9 m-1 and the backward
      attenuation is 1.4 m-1, so that the overall tapering effect gives a remarkably
      damped pressure response. For a natural taper angle of 0.14 degrees the
      perturbation is almost extinct when the pulse wave returns to the proximal
      extremity.

PMID- 1400536
TI  - Biomechanical properties of human lumbar spine ligaments.
AB  - Biomechanical properties of the six major lumbar spine ligaments were determined
      from 38 fresh human cadaveric subjects for direct incorporation into mathematical
      and finite element models. Anterior and posterior longitudinal ligaments, joint
      capsules, ligamentum flavum, interspinous, and supraspinous ligaments were
      evaluated. Using the results from in situ isolation tests, individual force
      deflection responses from 132 samples were transformed with a normalization
      procedure into mean force-deflection properties to describe the nonlinear
      characteristics. Ligament responses based on the mechanical characteristics as
      well as anatomical considerations, were grouped into T12-L2, L2-L4, and L4-S1
      levels maintaining individuality and nonlinearity. A total of 18 data curves are
      presented. Geometrical measurements of original length and cross-sectional area
      for these six major ligaments were determined using cryomicrotomy techniques.
      Derived parameters including failure stress and strain were computed using the
      strength and geometry information. These properties for the lumbar spinal
      ligaments which are based on identical definitions used in mechanical testing and
      geometrical assay will permit more realistic and consistent inputs for analytical
      models.

PMID- 1400538
TI  - A comparison between the inlet and outlet diameters of the normal aortic valve.
AB  - Two studies are described comparing the inlet and outlet diameters of the normal
      aortic valve. Both studies show the valve inlet to be smaller than the valve
      outlet. The first study is of measurements made on 12 casts of physiologically
      pressurised human aortic valves. The mean ratio between the diameter of the
      aortic ring and of the aorta just distal to the sinus ridge was 1.1, and the mean
      ratio between the diameter of the aortic ring and the maximum diameter of the
      valve leaflets was 1.18. The second study presents echocardiographic data from
      normal volunteers. The mean ratio between the diameter of the aortic ring and of
      the aorta just distal to the sinus ridge was 1.17. It is suggested that stents
      made to support the leaflets of prosthetic valves are made in conical or
      hyperbolic form, with the outlet being approximately 20% larger than the inlet.

PMID- 1400537
TI  - Evaluation of frontal radiographs of scoliotic spines--Part I. Measurement of
      position and orientation of vertebrae and assessment of clinical shape
      parameters.
AB  - A new method largely exploiting the shape information which may be obtained from
      frontal radiographs of scoliotic patients is presented. For a complete
      description of spinal deformity, six position parameters are needed for each
      vertebra. From a strictly mathematical point of view, none of them can be
      determined from a single standard radiograph. However, the four most important
      parameters can be measured if some reasonable assumptions are made. For a better
      interpretation, three of these parameters (lateral coordinate x, lateral tilt
      alpha and axial rotation rho) are plotted as a function of the fourth parameter,
      the longitudinal coordinate y. These functions may well be approximated by
      sinusoidal curves (or possibly by Fourier series). The data smoothing implied by
      this procedure improves the reliability of the data. The method has been tested
      with 478 radiographs of 113 patients (Cobb angles up to 52 degrees). The results
      are compared with scoliosis parameters which have been determined according to
      the conventional clinical rules. A particular advantage of approximation by a
      sinusoidal function lies in the direct relation of the curve parameters to common
      scoliosis parameters. Moreover, a mathematical analysis of the interrelations
      between different parameters--for example, between lateral deviation and axial
      rotation--is possible in this case.

PMID- 1400539
TI  - Biomch-L: an electronic mail discussion forum for biomechanics and movement
      science.

PMID- 1400540
TI  - Early and late loosening of the acetabular cup after low-friction arthroplasty.
AB  - Between 1971 and 1979, 680 low-friction arthroplasties of the hip were performed
      in 598 patients. The average duration of follow-up was twelve years and eight
      months. Sixty-one acetabular cups had loosening as seen on roentgenograms
      eighteen years postoperatively, resulting in a total cumulative probability of
      loosening of 19 per cent, according to survivorship analysis. In twenty-nine
      cups, the loosening appeared within ten years after the operation (early
      loosening) and in thirty-two, more than ten years after the operation (late
      loosening). Early loosening was associated with deficient structure of the bone
      of the acetabulum, a previous congenital dislocation of the hip, acetabular
      fracture, or acetabular protrusion in all instances (p < 0.01). Late loosening
      was associated with the depth of acetabular wear. Of the thirty-two cups that had
      more than two millimeters of wear, eighteen (56 per cent) had loosening on the
      roentgenograms (p < 0.001). In hips that had early loosening, migration was the
      most frequent finding, and its rate of progression was higher than in hips that
      had late loosening (p < 0.001). In late loosening, a complete bone-cement
      radiolucency of more than two millimeters was the most frequent finding. Clinical
      failure was seen in twenty-two (76 per cent) of the twenty-nine cups that
      loosened early and in nine (28 per cent) of the thirty-two cups that loosened
      late. The probability of extensive resorption of bone necessitates close
      observation of patients who have early loosening, while a reasonable period of
      observation is possible for those who have late loosening.

PMID- 1400541
TI  - The Harris-Galante porous-coated acetabular component with screw fixation.
      Radiographic analysis of eighty-three primary hip replacements at a minimum of
      five years.
AB  - The results of eighty-three consecutive primary total hip arthroplasties in which
      a Harris-Galante porous-coated acetabular component had been used were reviewed
      after a minimum of five years. In all patients, the stated diameter of the
      acetabular component (the diameter printed on the packaging for the implant) used
      was equal to the stated diameter of the reamer (the diameter printed on the
      reamer) that had been used last in the preparation of the acetabulum. As there
      was little or no press-fit stability, stability was obtained initially with
      multiple transfixing screws. No component was revised because of loosening, and
      none were radiographically loose at an average of sixty-eight months and a
      maximum of seven years after the operation. There was no evidence of disruption
      of the titanium porous mesh, and no screw had bent or broken. Two sockets,
      however, had been revised because of failure of the liner-locking mechanism as
      well as disassociation of the polyethylene liner from the titanium-alloy shell.
      Lysis of bone occurred in only one patient, around one screw. Areas of non
      contact (gaps) between the porous mesh at the periphery of the acetabular
      component and the bone were seen on the immediate postoperative radiographs of
      nearly half of the patients. New areas of radiolucency, which had not been seen
      immediately postoperatively, were identified at two years in forty-nine hips.
      These radiolucent lines were never wider than one millimeter and were most
      frequently located in zone 3 and, less frequently, in zone 1. At the time of the
      most recent follow-up evaluation, a progressive radiolucent line was identified
      around twenty-two components and a discontinuous radiolucent line was present in
      all three zones around eleven components. No continuous radiolucent line was
      identified at the mesh-bone interface of any component. These results are
      superior to our results with cemented acetabular components after a similar
      period of follow-up. A longer period of follow-up is needed before the importance
      of these thin radiolucent lines can be determined, but experience with cemented
      acetabular components indicates that progressive or extensive radiolucent lines,
      or both, may represent resorption of bone at the porous mesh-bone interface and
      this can lead to loosening of the component. Our data suggest that the technique
      used for implantation may be important not only for the initial fixation and
      ingrowth of bone, but also for the long-term durability of the fixation of a
      porous-coated acetabular component.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1400542
TI  - Prognostic factors in congenital dislocation of the hip treated with closed
      reduction. The importance of arthrographic evaluation.
AB  - We reviewed the clinical records, arthrograms, and roentgenograms of sixty-one
      children who had seventy-two congenitally dislocated hips in an effort to
      identify factors that can be used to predict the outcome of treatment. Only
      patients who had been followed clinically and roentgenographically for a minimum
      of two years after the initial closed reduction were included in the study. The
      mean age at the time of closed reduction was thirteen months (range, three to
      forty-one months). The mean age at the time of the most recent follow-up was six
      years (range, two to fifteen years). The mean duration of follow-up after the
      initial closed reduction was five years (range, two to thirteen years). There was
      no statistical difference between the good, fair, and poor-result groups with
      regard to sex, the age at the initial reduction, the traction station, the side
      of involvement, the initial acetabular index, the initial grade of displacement,
      the effect of adductor tenotomy, and several of the arthrographic measurements.
      The medialization ratio (the percentage of the horizontal radius of the
      cartilaginous femoral head that lay medial to the Perkins line), measured at the
      time of the reduction, was significantly different (p < 0.04) between the hips
      for which the result was good or fair and those for which the result was poor.
      The medialization ratio averaged 75 per cent in the hips for which the result was
      good, 66 per cent in those for which the result was fair, and 57 per cent in
      those for which the result was poor. Limbus shapes 5 through 8 were associated
      with avascular necrosis (p < 0.05) and a poor result (p < 0.03).

PMID- 1400544
TI  - Treatment of open fractures of the tibial shaft with the use of interlocking
      nailing without reaming.
AB  - Fifty open fractures of the tibial shaft that were treated with debridement and
      interlocking nailing without reaming were followed for an average of twelve
      months. Most of the fractures were the result of high-energy trauma, and 68 per
      cent of the fracture wounds were grade III. Forty-eight (96 per cent) of the
      fifty fractures united at an average of seven months; there were no malunions.
      There were four infections (8 per cent), all at the sites of grade-III fractures.
      Locking screws broke in five tibiae (10 per cent), but the breakage did not
      result in a loss of reduction. Three nails broke, two at the sites of ununited
      fractures and one at the site of a healed fracture. These results are comparable
      with, or better than, those obtained with other forms of fixation, including
      immobilization with a cast, unlocked intramedullary nailing, and external
      fixation.

PMID- 1400543
TI  - An intraosseous device for studies of bone-healing. The effect of transforming
      growth-factor beta.
AB  - A novel implantable device, the analytic bone implant, was used in order to
      establish a model for studies of bone-healing and the evaluation of factors that
      augment the process, such as transforming growth-factor beta (TGF-beta). This
      device was implanted into the tibiae of four baboons. After healing, bone was
      removed from the center chamber. Recombinant human TGF beta-1 was then delivered
      to the core of the device. After twenty-two days of healing, the device was
      disassembled and the newly formed bone was removed from the core of the implant
      for histomorphometric analysis. An analysis of the bone revealed a substantial
      effect of TGF-beta on osteoblastic activity and proliferation compared with that
      seen in control and placebo groups. However, despite increased osteoblastic
      activity, trabecular bone volumes at twenty-two days were equivalent among the
      groups. The number of osteoclasts and the erosion of the surface were also
      increased, although not significantly so. Substantial endochondral formation of
      bone was seen in the supraperiosteal tissues directly over the implants that
      contained TGF-beta but not over the implants in the control and placebo groups.
      These data demonstrate the utility of this bone-implant model for studies of bone
      healing with minimally invasive methods. In addition, use of the device provided
      the first in vivo data on the effects of TGF-beta at an intermediate (twenty-two
      day) time-point in the healing process in a non-human primate.

PMID- 1400545
TI  - Continued growth of the proximal part of the tibia after prosthetic
      reconstruction of the skeletally immature knee. Estimation of the minimum growth
      force in vivo in humans.
AB  - We studied five skeletally immature patients who had a cemented endoprosthetic
      replacement involving the proximal part of the tibia because of a malignant
      tumor. In each patient, the cement-column fractured, allowing additional physeal
      growth. With plain radiographs and scanograms, we determined the cross-sectional
      areas of the physes, the cement-mantle, and the tibial component. Using the known
      tensile strength of polymethylmethacrylate cement, we then calculated the minimum
      force that the growth plates must have overcome to fracture the cement. This
      averaged 584 newtons per square centimeter. This observation of continued tibial
      growth after partial physeal ablation with a cemented prosthesis in skeletally
      immature patients presented a unique opportunity to estimate the force generated
      in the human physis during growth.

PMID- 1400546
TI  - Palsy of the deep peroneal nerve after proximal tibial osteotomy. An anatomical
      study.
AB  - Iatrogenic, isolated weakness or paralysis of the extensor hallucis longus muscle
      is a common complication in patients who have had a proximal tibial and fibular
      osteotomy. To investigate why this complication occurs, we dissected the deep
      peroneal nerve and neighboring structures, such as the tibia and fibula and the
      muscles of the leg, in twenty-nine specimens from cadavera, paying special
      attention to the motor branches supplying the extensor hallucis longus. Of forty
      six motor nerves that were identified, eight entered the muscle from the lateral
      side in an area seventy to 150 millimeters distal to the fibular head; all of
      them ran close to the fibular periosteum. We suggest that, in some patients, the
      nerve supply to the extensor hallucis longus is at high risk for injury during a
      tibial osteotomy because of the proximity of the bone to the motor branches.

PMID- 1400547
TI  - Lateral meniscal variant with absence of the posterior coronary ligament.
AB  - We reviewed the cases of 3468 patients who had had arthroscopy of the knee
      between January 1976 and December 1988. Twenty-six patients (0.8 per cent) had a
      partial or a complete discoid lateral meniscus, and seven (0.2 per cent) had the
      Wrisberg-variant-type lateral meniscus. Of the seven patients, six had operative
      stabilization of the meniscus and one had a partial lateral meniscectomy because
      of an irreparable complex tear. Subjective, objective, and radiographic
      evaluations were performed on the patients who had had stabilization of the
      meniscus. According to the scale of Tegner and Lysholm, the result was excellent
      in four patients, good in one, and fair in one. None of the six patients had a
      tear of the sutured meniscus after an average follow-up of thirty-two months
      (range, twenty-four to forty months). Two patients had progressive symptoms
      attributable to osteoarthrosis, but the changes in the articular cartilage had
      been present at the time of the index procedure. None of the seven Wrisberg
      variant-type menisci demonstrated a true discoid shape of the meniscus. We
      therefore classified this lesion as a lateral meniscal variant with absence of
      the posterior coronary ligament.

PMID- 1400548
TI  - Revision of ankle arthrodesis with external fixation for non-union.
AB  - We evaluated the cases of twenty-six patients (twenty-six ankles) who had had
      revision of an ankle arthrodesis with external fixation for a nonunion, to
      determine the reasons for the failure of the previous arthrodesis. Eighteen
      patients had had supplemental bone-grafting in addition to the external fixation.
      The failure of the previous arthrodesis was related to inadequate fixation
      technique in seven patients and to technical problems in two patients; in the
      other seventeen patients at least one risk factor was identified. We also
      determined the functional results of the revision operation with external
      fixation for all patients. The average duration of follow-up was five years
      (range, two to ten years) in the twenty-two patients who did not have a
      reoperation for a persistent nonunion. The results were excellent in eleven
      patients, good in five, fair in four, and poor in six. The over-all rate of union
      was twenty (77 per cent) of twenty-six, comparable with that after primary
      arthrodesis; however, supplemental bone-grafting is usually necessary. In the
      current series, rigid fixation, precise apposition of bone and alignment of the
      foot, and early treatment of perioperative infection gave satisfactory results.

PMID- 1400549
TI  - Assessment of the posterior malleolus as a restraint to posterior subluxation of
      the ankle.
AB  - We assessed the function of the posterior malleolus, the anterior tibiofibular
      ligament, and the fibula with regard to posterior stability of the talus in ten
      ankles of cadavera. Posteriorly directed loads of as much as 200 newtons were
      applied. Two groups of ankles were tested; in the first group, three ankles in
      which the ligamentous and osseous structures were intact were tested after
      transection of the posterior capsule and after removal of 10, 20, 30, and 40 per
      cent of the articular surface of the distal end of the tibia from the
      posterolateral corner. In the second group, seven ankles were tested in the same
      sequence, but the anterior tibiofibular ligament and the fibula were transected
      before sectioning of the articular surface. Compared with the results for the
      intact ankle, the experiments on the first group demonstrated less than one
      millimeter of additional posterior translation of the talus after removal of as
      much as 40 per cent of the articular surface. In the second group, in which the
      anterior tibiofibular ligament and the fibula had been transected, significant
      posterior translation of the talus (more than three millimeters) occurred after
      removal of 30 per cent of the articular surface (p < 0.01). This represented a
      160 per cent increase in translation compared with that in the intact ankle.

PMID- 1400550
TI  - Long-term results after Russe bone-grafting: the effect of malunion of the
      scaphoid.
AB  - Twenty-five patients had Russe anterior corticocancellous bone-grafting between
      1973 and 1984 for twenty-six symptomatic established non-unions of the scaphoid.
      The mean duration of follow-up was eleven years (range, seven to eighteen years).
      Twenty-one (81 per cent) of the twenty-six scaphoid bones united. We developed
      two rating scales to evaluate the results of the operation. One scale, based on
      objective findings, included the radiographic appearance of the wrist, the range
      of motion, and strength; the other scale, based on subjective findings, comprised
      function, pain, perception of a decrease in performance because of limitation of
      motion or strength, and satisfaction. These scales were used to compare the
      objective and subjective results in patients who had a malunion of the scaphoid
      in which the lateral intrascaphoid angle was more than 45 degrees convex dorsally
      between the proximal and distal poles (a so-called flexion or humpback deformity,
      which results in extension of the proximal fragment of the scaphoid at the
      radiocarpal joint) with the results in patients who had no such deformity. The
      lateral intrascaphoid angle was more than 45 degrees in thirteen (50 per cent) of
      the twenty-six wrists. Although the difference in the objective results between
      the wrists that had a malunion and those that did not have a malunion was highly
      significant (p = 0.001), there was no significant difference in the subjective
      results between the two groups, including satisfaction of the patient (p = 0.39).
      Twenty-three patients (92 per cent) returned to full-time employment and twenty
      two (88 per cent), to sports activities. Twenty-three patients (92 per cent)
      reported that they had pronounced relief of pain and that the procedure had
      improved their quality of life. The presence of this deformity of the scaphoid
      after bone-grafting for a symptomatic non-union was not predictive of a poor long
      term subjective outcome.

PMID- 1400552
TI  - Ligamentous reconstruction for posterolateral rotatory instability of the elbow.
AB  - Eleven consecutively seen patients who had posterolateral rotatory instability of
      the elbow joint were managed operatively. The radial collateral-ligament complex
      was advanced and imbricated in three of them. In seven patients, the ulnar band
      of the radial collateral ligament (the lateral ulnar collateral ligament) was
      reconstructed with the palmaris longus tendon and in two of the seven, the
      reconstruction was augmented with a prosthetic ligament. The ligament was
      reconstructed with the lateral one-third of the triceps fascia in the remaining
      patient. Stability was obtained in ten patients, and seven patients had an
      excellent functional result. There was one failure in one of the patients in whom
      the ulnar band of the radial collateral ligament had been reconstructed with the
      palmaris longus tendon and augmented with a prosthetic ligament.

PMID- 1400551
TI  - Anterior capsulotomy and continuous passive motion in the treatment of post
      traumatic flexion contracture of the elbow. A prospective study.
AB  - Thirty-three patients who had a post-traumatic flexion contracture of the elbow
      were managed consecutively with anterior capsulotomy without tenotomy of the
      biceps tendon or myotomy of the brachialis muscle. The first fifteen patients
      (Group I) did not receive continuous passive motion postoperatively. Preoperative
      active extension for Group I was to an average of 48 degrees short of full
      extension, which improved to 19 degrees at a mean follow-up time of forty-five
      months. Subsequently, eighteen patients (Group II) received continuous passive
      motion postoperatively for a mean of six weeks. Preoperative active extension for
      Group II was to an average of 55 degrees short of full extension, which improved
      to 23 degrees at a mean duration of follow-up of thirty-five months. The mean
      preoperative arc of motion for Group I was 69 degrees, which improved to 94
      degrees postoperatively. The mean preoperative arc of motion for Group II was 48
      degrees, which improved to 95 degrees postoperatively. Five patients in Group I
      and six patients in Group II had severe preoperative heterotopic ossification.
      There was no correlation, however, between preoperative heterotopic ossification
      and the amount that extension of the elbow improved postoperatively. There was no
      postoperative increase in heterotopic ossification. Four patients in Group I and
      six patients in Group II had severe post-traumatic osteoarthrosis preoperatively.
      Anterior capsulotomy is an effective treatment of post-traumatic flexion
      contracture of the elbow. Although the postoperative use of continuous passive
      motion did not significantly improve mean active extension, it did improve active
      flexion and the total arc of motion.

PMID- 1400554
TI  - A technique for removal of cannulated screws with buried heads from the femoral
      neck in the course of total hip replacement. A brief note.

PMID- 1400553
TI  - The fate of traumatic anterior dislocation of the shoulder in children.
AB  - The cases of twenty-one patients who had open physes and were treated for
      radiographic evidence of traumatic anterior dislocation of the shoulder at either
      the Adelaide Childrens Hospital or The Hospital for Sick Children, Toronto,
      during a fifteen-year period, were reviewed. All twenty-one patients had had one
      or more recurrent dislocations. Treatment, which included immobilization in a
      sling and swathe for as long as six weeks, had no effect on the rate of
      recurrence.

PMID- 1400555
TI  - Multiple fractures in a child: the osteoporosis pseudoglioma syndrome. A case
      report.

PMID- 1400556
TI  - Tibia vara. Report of an unusual case.

PMID- 1400557
TI  - Severe destructive polyarthropathy in association with a metabolic storage
      disease. A case report.

PMID- 1400558
TI  - The early diagnosis of transient osteoporosis by magnetic resonance imaging. A
      case report.

PMID- 1400559
TI  - Autologous-blood transfusion: the reimbursement dilemma.

PMID- 1400560
TI  - Use of a hinged silicone prosthesis for replacement arthroplasty of the first
      metatarsophalangeal joint.

PMID- 1400561
TI  - False-negative biopsy for testicular intraepithelial neoplasia.
AB  - A routine biopsy of the contralateral testis obtained during orchiectomy for
      embryonal carcinoma in a 26-year-old patient was negative for testicular
      intraepithelial neoplasia (TIN; carcinoma in situ of the testis). However, a
      rebiopsy that was taken because of unexplained elevation of alpha-fetoprotein 15
      months later proved to be positive for TIN. Six previously reported cases of
      false-negative testicular biopsies obtained during a search for TIN are reviewed.
      In the light of several thousands of biopsies performed world-wide to date, the
      number of false-negative biopsies is probably very low. Although TIN is obviously
      not randomly dispersed throughout the testis in all patients, a routine biopsy of
      the contralateral testicle in patients with testis cancer remains a valuable tool
      for early detection of bilateral testicular tumors.-cal distribution of TIN in
      testes removed for this lesion. Their results suggested that after puberty TIN is
      usually randomly dispersed throughout the testicle. Support for this concept was
      recently given by Mumperow et al. (1992). These authors examined tumor-bearing
      testes and they did not find differences in the presence of TIN in biopsies taken
      from a location close to the tumor and taken from a location distant from the
      tumor. Thus, one single biopsy is regard to be representative for the entire
      testis and one biopsy taken after puberty is also assumed to be reliable for
      predicting whether the testis will ever develop cancer (Berthelsen and Skakkebaek
      1981 a). Conversely, if the biopsy is negative for TIN, a future tumor
      manifestation in the testicle examined is not expected according to this theory
      (Skakkebaek et al. 1987). Taken together, the concept of TIN would constitute an
      ideal avenue for the early detection of testis cancer in high-risk populations
      with the biopsy being a safe means of discriminating between individuals who will
      or who will not develop testis cancer.

PMID- 1400563
TI  - Establishment and characterization of a new human oestradiol- and progesterone
      receptor-positive mammary carcinoma serially transplantable in nude mice.
AB  - A human mammary carcinoma originating from a postmenopausal patient was
      successfully transplanted into nude mice. According to the adopted criteria the
      tumour proved to be oestradiol- and progesterone-receptor-positive. Histological
      studies of the patient tumour revealed a ductal invasive mammary carcinoma with
      80% tubular growth pattern. Following transplantation the adenoid structures
      decreased to 30%; the mitosis rate and grade of malignancy increased. Treatment
      of the nude mice with 20 micrograms oestradiol benzoate/mouse caused a loss of
      the oestradiol receptor of the mammary carcinoma. The mammary carcinoma 3366 can
      be used for testing of antineoplastic substances, antihormones and for studies in
      regard to down-regulation or blocking of hormone receptors and possible
      consequences for therapies.

PMID- 1400562
TI  - Radiation sensitivities in various anticancer-drug-resistant human lung cancer
      cell lines and mechanism of radiation cross-resistance in a cisplatin-resistant
      cell line.
AB  - To determine whether there exists cross-resistance between anticancer drugs and
      radiation, six drug-resistant human lung cancer cell lines and their parental
      cell lines were examined for radiosensitivity using a growth-inhibition assay.
      Only one cisplatin-resistant cell line, PC-9/CDDP, showed cross-resistance to
      radiation. The other three cisplatin-resistant cell lines (PC-7/CDDP, PC-4/CDDP,
      and H69/CDDP), an etoposide-resistant cell line (H69/VP) and a camptothecin
      resistant cell line (PC-7/CPT) did not show cross-resistance to radiation. To
      analyze the mechanism of radiation resistance in PC-9/CDDP cells, the formation
      and repair of radiation-induced DNA single-strand breaks (ssb) and double-strand
      breaks (dsb) were examined by alkaline elution and neutral elution respectively.
      Although the formation of DNA ssb and repair of both DNA ssb and DNA dsb were the
      same for both cell lines, the formation of DNA dsb in PC-9/CDDP cells was
      significantly less than those in PC-9 cells. Measurement of intracellular
      glutathione content in all of the cell lines revealed that only PC-9/CDDP cells
      had a significant increase of glutathione content compared to the parental cells.
      Buthionine sulfoximine treatment of PC-9/CDDP cells caused an increase of DNA dsb
      to the same levels as in PC-9 cells after irradiation and caused a complete
      radiosensitization. These results indicate that cross-resistance to radiation in
      drug-resistant cells in a rare phenomenon, and increased glutathione content may
      play a crucial role in the emergence of cross-resistance to radiation in the drug
      resistant cells.

PMID- 1400564
TI  - Toxicity associated with the formation and clearance of immune complexes between
      antitumour monoclonal antibodies and syngeneic anti-idiotypic antibodies in mice.
AB  - We have previously shown that Balb/c mice immunised against syngeneic monoclonal
      antibodies (mAbs), so that they have anti-idiotypic responses against those mAbs,
      will clear the mAbs from the circulation as a result of immune complex formation.
      We report here that with three separate mAbs, this clearance of complexes can
      result in toxicity to the animals. This was particularly severe with one mAb
      (NCRC-2), in some cases leading to death. It was not seen with Fab/c or Fab
      fragments of NCRC-2. This toxic response could be passively transferred with
      serum, indicating that it was due to formation of immune complexes or to their
      subsequent clearance. Treatment of mice with cobra venom factor, to reduce
      complement levels, reduced clearance of complexes but had no effect on toxicity.
      The anti-histamine pyrilamine did not reduce toxicity. This is one of only a few
      situations in which an anti-(mouse antibody) response has been reported to be
      potentially dangerous, and is particularly remarkable since it occurs as a result
      of such a limited anti-antibody response.

PMID- 1400565
TI  - Suppression of human nasopharyngeal carcinoma cell growth in nude mice by the
      wild-type p53 gene.
AB  - Wild-type and mutant human p53 genes were transfected into the nasopharyngeal
      carcinoma (NPC) cell line CNE-3. Tumorigenicity in nude mice showed that the
      tumor resulting from the cells transfected with the wild-type p53 gene grew more
      slowly and was smaller than that from the cells transfected with mutant p53 gene
      and that from control CNE-3 cells. In contrast, the tumor from the cells
      transfected with the mutant p53 gene grew faster than that produced by cells
      transfected with the wild-type p53 gene and that produced by control CNE-3 cells.
      The results demonstrate that the wild-type p53 gene could inhibit the NPC cell
      growth in nude mice and the mutant p53 gene could enhance the NPC cell growth in
      nude mice. The p53 gene may also play an important role in the pathogenesis of
      NPC.

PMID- 1400567
TI  - Partial responses to antineoplastic drug therapy: what do they mean?

PMID- 1400566
TI  - Argyrophilic nucleolar organizer regions in human adrenocortical neoplasms.
AB  - Argyrophilic nucleolar organizer regions (AgNOR) in human adrenocortical
      neoplasms, including five carcinomas and ten adenomas, were studied using a semi
      automatic image analyzer. Both the number and total area of AgNOR per nucleus in
      the carcinomas were found to be statistically greater than in adenomas and
      control tissues. However, there were no statistically significant differences in
      total AgNOR area per nuclear area or in the mean area of individual AgNOR dots.
      The AgNOR of neoplastic and normal cells were of four morphological types: type 1
      had a few dots at the periphery of the nucleus, type 2 a few dots at the center,
      type 3 a large round dot along with several small ones at the center, and type 4
      numerous diffusely distributed polymorphic dots. Most type 3 and 4 cells were
      found in carcinoma cases. Type 1 cells decreased in proportion to the severity of
      biological malignancy. It follows from these findings that careful observation of
      AgNOR should facilitate the distinction of malignant from benign adrenocortical
      neoplasms.

PMID- 1400568
TI  - Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum
      refractory ovarian cancer.
AB  - Eighteen previously treated patients with advanced ovarian cancer were entered
      into a phase 2 trial of chronic low-dose oral etoposide (50 mg/day for 20 days,
      repeated every 28 days) to determine the activity of this therapeutic strategy in
      organoplatinum-refractory disease. The treatment program was generally well
      tolerated, with mild neutropenia the most common side-effect encountered. One
      patient (6%; 95% confidence interval = 0-17%) achieved a partial response, which
      lasted for 11 months. Three additional patients (17%), who failed to meet the
      criteria of a partial response, demonstrated objective evidence of antineoplastic
      activity. Chronic low-dose oral etoposide administration is associated with
      definite, although modest, activity in platinum-refractory ovarian cancer.

PMID- 1400569
TI  - Calcitonin therapy of aneurysmal bone cysts.
AB  - Seven aneurysmal bone cysts (ABC) were treated with the hormone calcitonin. Six
      of the cysts, which were hypovascular responded well to the calcitonin
      administered directly into the cyst. Ossification and rebuilding of the ABC
      occurred after some months in every case. One hypervascularized ABC, however,
      failed to respond either to embolo-therapy or to the calcitonin hormone
      treatment. The authors recommend calcitonin administration as a useful non
      invasive method for the treatment of hypovascular ABC.

PMID- 1400571
TI  - The cytoplasmic tail of the mannose 6-phosphate/insulin-like growth factor-II
      receptor has two signals for lysosomal enzyme sorting in the Golgi.
AB  - The mannose 6-phosphate/insulin-like growth factor-II (Man-6-P/IGF-II) receptor
      is known to cycle between the Golgi, endosomes, and the plasma membrane. In the
      Golgi the receptor binds newly synthesized lysosomal enzymes and transports them
      directly to an endosomal (prelysosomal) compartment without traversing the plasma
      membrane. Deletion of the carboxyl-terminal Leu-Leu-His-Val residues of the 163
      amino acid cytoplasmic tail of the bovine Man-6-P/IGF-II receptor partially
      impaired this function, resulting in the diversion of a portion of the receptor
      ligand complexes to the cell surface, where they were endocytosed. The same
      phenotype was observed when 134 residues of the cytoplasmic tail were deleted
      from the carboxyl terminus. Disruption of the Tyr24-Lys-Tyr-Ser-Lys-Val29 plasma
      membrane internalization signal alone had little effect on Golgi sorting, but
      when combined with either deletion resulted in a complete loss of this function.
      The mutant receptors retained the ability to recycle to the Golgi and bind
      cathepsin D. These results indicate that the cytoplasmic tail of the Man-6-P/IGF
      II receptor contains two signals that contribute to Golgi sorting, presumably by
      interacting with the Golgi clathrin-coated pit adaptor proteins. The Leu-Leu
      containing sequence represents a novel motif for mediating interaction with Golgi
      adaptor proteins.

PMID- 1400572
TI  - Effects of brefeldin A on endocytosis, transcytosis and transport to the Golgi
      complex in polarized MDCK cells.
AB  - We have studied the effects of brefeldin A (BFA) on endocytosis and intracellular
      traffic in polarized MDCK cells by using the galactose-binding protein toxin
      ricin as a membrane marker and HRP as a marker of fluid phase transport. We found
      that BFA treatment rapidly increased apical endocytosis of both ricin and HRP,
      whereas basolateral endocytosis was unaffected, as was endocytosis of HRP in the
      poorly polarized carcinoma cell lines HEp-2 and T47D. Tubular endosomes were
      induced by BFA both apically and basolaterally in some MDCK cells, comparable
      with those seen in HEp-2 and T47D cells. In addition, in MDCK cells, BFA induced
      formation of small (< 300 nm) vesicles, labeled both after apical and basolateral
      uptake of HRP, as well as some very large (> 700 nm) vacuoles, which were only
      labeled when HRP was present in the apical medium. In contrast, neither in MDCK
      nor in HEp-2 or T47D cells, did BFA have any effect on lysosomal morphology.
      Moreover, transcytosis in the basolateral-apical direction was stimulated both
      for HRP and ricin. Other vesicular transport routes were less affected or
      unaffected by BFA treatment. Two closely related structural analogues of BFA (B16
      and B21), unable to produce the changes in Golgi and endosomal morphology seen
      after BFA treatment in a number of different cell lines, were also unable to
      mimic the effects of BFA on MDCK cells.

PMID- 1400573
TI  - The morphology but not the function of endosomes and lysosomes is altered by
      brefeldin A.
AB  - Brefeldin A (BFA) induces the formation of an extensively fused network of
      membranes derived from the trans-Golgi network (TGN) and early endosomes (EE). We
      describe in detail here the unaffected passage of endocytosed material through
      the fused TGN/EE compartments to lysosomes in BFA-treated cells. We also
      confirmed that BFA caused the formation of tubular lysosomes, although the
      kinetics and extent of tubulation varied greatly between different cell types.
      The BFA-induced tubular lysosomes were often seen to form simple networks.
      Formation of tubular lysosomes was microtubule-mediated and energy-dependent;
      interestingly, however, maintenance of the tubulated lysosomes only required
      microtubules and was insensitive to energy poisons. Upon removal of BFA, the
      tubular lysosomes rapidly recovered in an energy-dependent process. In most cell
      types examined, the extensive TGN/EE network is ephemeral, eventually collapsing
      into a compact cluster of tubulo-vesicular membranes in a process that precedes
      the formation of tubular lysosomes. However, in primary bovine testicular cells,
      the BFA-induced TGN/EE network was remarkably stable (for > 12 h). During this
      time, the TGN/EE network coexisted with tubular lysosomes, however, the two
      compartments remained completely separate. These results show that BFA has
      multiple, profound effects on the morphology of various compartments of the
      endosome-lysosome system. In spite of these changes, endocytic traffic can
      continue through the altered compartments suggesting that transport occurs
      through noncoated vesicles or through vesicles that are insensitive to BFA.

PMID- 1400570
TI  - Primary central nervous system lymphomas--an update.
AB  - Primary CNS lymphomas (PCNSL), until recently representing about 1% of all brain
      tumors, show dramatically increased incidence both in high-risk groups
      (immunocompromised, AIDS) and in the general population. They are extranodal
      diffuse non-Hodgkin's lymphomas, the morphology and classification of which are
      identical to those of systemic lymphomas, although PCNSL show different
      biological behavior and diagnosis according to the New Working Formulation and
      updated Kiel classification may be difficult. The majority are large B cell
      variants of high-grade malignancy; low-grade subtypes and T cell lymphomas are
      rare. Sixty per cent occur in the supratentorial space (hemispheres,
      periventricular) and 12% in the posterior fossa; 30% are multiple (50%-70% in
      AIDS). PCNSL show a male preponderance with a peak incidence in the 5th-7th
      decade (3rd-4th in AIDS). The duration of diffuse or focal clinical symptoms
      averages 1-2 months. Computed tomography and magnetic resonance imaging scans
      show single or multiple or diffuse, often typical lesions. Diagnosis is achieved
      by evaluation of stereotactic biopsy material or cerebrospinal fluid cytology
      using immunocytological markers. Current therapy in immunocompetent patients,
      radiation plus corticosteroids and pre- or postradiation polychemotherapy, shows
      response rates of 85% with a median survival of 17-44 months, a prognosis similar
      to that for glioblastoma. Meningeal PCNSL is treated with intrathecal
      methotrexate or cytosine arabinoside. Transliquoral seeding of PCNSL is frequent,
      distant metastases occurring in 6%-8%. Therapy of AIDS-related PCNSL makes use of
      radiation and corticosteroids, and rarely of chemotherapy. The pathogenesis of
      PCNSL is unknown, but Epstein-Barr virus may be a contributory factor.

PMID- 1400575
TI  - Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions
      for its induction.
AB  - For determination of the physiological role and mechanism of vacuolar proteolysis
      in the yeast Saccharomyces cerevisiae, mutant cells lacking proteinase A, B, and
      carboxypeptidase Y were transferred from a nutrient medium to a synthetic medium
      devoid of various nutrients and morphological changes of their vacuoles were
      investigated. After incubation for 1 h in nutrient-deficient media, a few
      spherical bodies appeared in the vacuoles and moved actively by Brownian
      movement. These bodies gradually increased in number and after 3 h they filled
      the vacuoles almost completely. During their accumulation, the volume of the
      vacuolar compartment also increased. Electron microscopic examination showed that
      these bodies were surrounded by a unit membrane which appeared thinner than any
      other intracellular membrane. The contents of the bodies were morphologically
      indistinguishable from the cytosol; these bodies contained cytoplasmic ribosomes,
      RER, mitochondria, lipid granules and glycogen granules, and the density of the
      cytoplasmic ribosomes in the bodies was almost the same as that of ribosomes in
      the cytosol. The diameter of the bodies ranged from 400 to 900 nm. Vacuoles that
      had accumulated these bodies were prepared by a modification of the method of
      Ohsumi and Anraku (Ohsumi, Y., and Y. Anraku. 1981. J. Biol. Chem. 256:2079
      2082). The isolated vacuoles contained ribosomes and showed latent activity of
      the cytosolic enzyme glucose-6-phosphate dehydrogenase. These results suggest
      that these bodies sequestered the cytosol in the vacuoles. We named these
      spherical bodies "autophagic bodies." Accumulation of autophagic bodies in the
      vacuoles was induced not only by nitrogen starvation, but also by depletion of
      nutrients such as carbon and single amino acids that caused cessation of the cell
      cycle. Genetic analysis revealed that the accumulation of autophagic bodies in
      the vacuoles was the result of lack of the PRB1 product proteinase B, and
      disruption of the PRB1 gene confirmed this result. In the presence of PMSF, wild
      type cells accumulated autophagic bodies in the vacuoles under nutrient-deficient
      conditions in the same manner as did multiple protease-deficient mutants or cells
      with a disrupted PRB1 gene. As the autophagic bodies disappeared rapidly after
      removal of PMSF from cultures of normal cells, they must be an intermediate in
      the normal autophagic process. This is the first report that nutrient-deficient
      conditions induce extensive autophagic degradation of cytosolic components in the
      vacuoles of yeast cells.

PMID- 1400574
TI  - Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole
      independent of the secretory pathway.
AB  - The Saccharomyces cerevisiae APE1 gene product, aminopeptidase I (API), is a
      soluble hydrolase that has been shown to be localized to the vacuole. API lacks a
      standard signal sequence and contains an unusual amino-terminal propeptide. We
      have examined the biosynthesis of API in order to elucidate the mechanism of its
      delivery to the vacuole. API is synthesized as an inactive precursor that is
      matured in a PEP4-dependent manner. The half-time for processing is approximately
      45 min. The API precursor remains in the cytoplasm after synthesis and does not
      enter the secretory pathway. The precursor does not receive glycosyl
      modifications, and removal of its propeptide occurs in a sec-independent manner.
      Neither the precursor nor mature form of API are secreted into the extracellular
      fraction in vps mutants or upon overproduction, two additional characteristics of
      soluble vacuolar proteins that transit through the secretory pathway.
      Overproduction of API results in both an increase in the half-time of processing
      and the stable accumulation of precursor protein. These results suggest that API
      enters the vacuole by a posttranslational process not used by most previously
      studied resident vacuolar proteins and will be a useful model protein to analyze
      this alternative mechanism of vacuolar localization.

PMID- 1400576
TI  - Immunocytochemical localization of alpha-protein kinase C in rat pancreatic beta
      cells during glucose-induced insulin secretion.
AB  - To investigate the role of protein kinase C (PKC) in the regulation of insulin
      secretion, we visualized changes in the intracellular localization of alpha-PKC
      in fixed beta-cells from both isolated rat pancreatic islets and the pancreas of
      awake unstressed rats during glucose-induced insulin secretion. Isolated,
      perifused rat islets were fixed in 4% paraformaldehyde, detergent permeabilized,
      and labeled with a mAb specific for alpha-PKC. The labeling was visualized by
      confocal immunofluorescent microscopy. In isolated rat pancreatic islets
      perifused with 2.75 mM glucose, alpha-PKC immunostaining was primarily
      cytoplasmic in distribution throughout the beta-cells. In islets stimulated with
      20 mM glucose, there was a significant redistribution of alpha-PKC to the cell
      periphery. This glucose-induced redistribution was abolished when either
      mannoheptulose, an inhibitor of glucose metabolism, or nitrendipine, an inhibitor
      of calcium influx, were added to the perifusate. We also examined changes in the
      intracellular distribution of alpha-PKC in the beta-cells of awake, unstressed
      rats that were given an intravenous infusion of glucose. Immunocytochemical
      analysis of pancreatic sections from these rats demonstrated a glucose-induced
      translocation of alpha-PKC to the cell periphery of the beta-cells. These results
      demonstrate that the metabolism of glucose can induce the redistribution of alpha
      PKC to the cell periphery of beta-cells, both in isolated islets and in the
      intact animal, and suggest that alpha-PKC plays a role in mediating glucose
      induced insulin secretion.

PMID- 1400577
TI  - Structural changes and lateral redistribution of photosystem II during donor side
      photoinhibition of thylakoids.
AB  - The structural and topological stability of thylakoid components under
      photoinhibitory conditions (4,500 microE.m-2.s-1 white light) was studied on Mn
      depleted thylakoids isolated from spinach leaves. After various exposures to
      photoinhibitory light, the chlorophyll-protein complexes of both photosystems I
      and II were separated by sucrose gradient centrifugation and analysed by Western
      blotting, using a set of polyclonals raised against various apoproteins of the
      photosynthetic apparatus. A series of events occurring during donor side
      photoinhibition are described for photosystem II, including: (a) lowering of the
      oligomerization state of the photosystem II core; (b) cleavage of 32-kD protein
      D1 at specific sites; (c) dissociation of chlorophyll-protein CP43 from the
      photosystem II core; and (d) migration of damaged photosystem II components from
      the grana to the stroma lamellae. A tentative scheme for the succession of these
      events is illustrated. Some effects of photoinhibition on photosystem I are also
      reported involving dissociation of antenna chlorophyll-proteins LHCI from the
      photosystem I reaction center.

PMID- 1400579
TI  - The subcellular distribution of chromosome 6-encoded dystrophin-related protein
      in the brain.
AB  - Chromosome 6-encoded dystrophin-related-protein (DRP) shows significant
      structural similarities to dystrophin at the carboxyl terminus, though the two
      proteins are encoded on different chromosomes. Both DRP and dystrophin are
      expressed in muscle and brain and show some similarity in their subcellular
      localization. For example, in skeletal muscle both are expressed at neuromuscular
      and myotendinous junctions. However, while dystrophin is absent or severely
      reduced in Duchenne/Becker muscular dystrophy, DRP continues to be expressed.
      Within the brain, dystrophin is enriched at the postsynaptic regions of specific
      subsets of neurons, while the distribution of DRP is yet to be described. In this
      study we demonstrate a distinct though highly specific pattern of distribution of
      DRP in the brain. DRP is enriched in the choroid plexus, pia mater, intracerebral
      vasculature, and ependymal lining. Within the parenchyma proper, DRP is located
      at the inner plasma face of astrocytic foot processes at the abluminal aspect of
      the blood-brain barrier. The distribution of DRP is conserved across a large
      evolutionary distance, from mammals to elasmobranchs, suggesting that DRP may
      play a role in the maintenance of regional specializations in the brain.

PMID- 1400578
TI  - The cytoskeleton and the cellular traffic of the progesterone receptor.
AB  - Previous studies on glucocorticoid receptors have suggested the existence of
      interactions between the receptor and microtubule or actin networks. It was
      hypothesized that such interactions may contribute to the guidance of steroid
      hormone receptors towards the nucleus. We used a permanent L cell line expressing
      the delta 638-642 progesterone receptor. This mutant has all the characteristics
      of the wild type receptor except that the deletion of five amino acids
      inactivates the constitutive karyophilic signal. Consequently, the receptor is
      cytoplasmic in the absence of hormone but is shifted into the nucleus when
      administration of hormone activates the second karyophilic signal. Optical
      microscopy and confocal laser microscopy were used in intact cells or in cells
      depleted of soluble elements by permeabilization with detergents. By
      immunofluorescence, the receptor was found to be mainly concentrated in the
      perinuclear area. A small fraction of progesterone receptor (PR) persisted in
      this region after Triton X100 treatment. These observations suggested that the
      receptor could interact with some insoluble constituent(s) of the cytoplasm.
      However, careful colocalization studies showed that this heterogenous
      distribution was not due to interactions with microtubule, microfilament, or
      intermediate filament networks. Functional involvement of these networks in the
      translocation of the receptor into the nucleus was studied after cell treatment
      with cytoskeletal drugs such as nocodazole, demecolcine and cytochalasin. None of
      these compounds prevented or even delayed the hormone-dependent transfer of delta
      638-642 PR into the nucleus. Similar conclusions were reached with the wild type
      receptor expressed by transfection in Cos-7 cells. PR was shifted from the
      nucleus into the cytoplasm by administration of energy-depleting drugs. After
      disruption of the various cytoskeletal networks normal nuclear reaccumulation of
      the receptor was observed when these drugs were removed. The results thus suggest
      that the progesterone receptor is not colocalized with the main cytoskeletal
      components. Disruption of the cytoskeletal networks does not prevent its nuclear
      translocation. Thus, karyophilic signals and interactions with the nuclear pore
      seem to be the primary determinants of the cellular traffic of the progesterone
      receptor.

PMID- 1400580
TI  - Comparison of actin and cell surface dynamics in motile fibroblasts.
AB  - We have investigated the dynamic behavior of actin in fibroblast lamellipodia
      using photoactivation of fluorescence. Activated regions of caged resorufin (CR)
      labeled actin in lamellipodia of IMR 90 and MC7 3T3 fibroblasts were observed to
      move centripetally over time. Thus in these cells, actin filaments move
      centripetally relative to the substrate. Rates were characteristic for each cell
      type; 0.66 +/- 0.27 microns/min in IMR 90 and 0.36 +/- 0.16 microns/min in MC7
      3T3 cells. In neither case was there any correlation between the rate of actin
      movement and the rate of lamellipodial protrusion. The half-life of the activated
      CR-actin filaments was approximately 1 min in IMR 90 lamellipodia, and
      approximately 3 min in MC7 3T3 lamellipodia. Thus continuous filament turnover
      accompanies centripetal movement. In both cell types, the length of time required
      for a section of the actin meshwork to traverse the lamellipodium was several
      times longer than the filament half-life. The dynamic behavior of the dorsal
      surface of the cell was also observed by tracking lectin-coated beads on the
      surface and phase-dense features within lamellipodia of MC7 3T3 cells. The
      movement of these dorsal features occurred at rates approximately three times
      faster than the rate of movement of the underlying bulk actin cytoskeleton, even
      when measured in the same individual cells. Thus the transport of these dorsal
      features must occur by some mechanism other than simple attachment to the moving
      bulk actin cytoskeleton.

PMID- 1400581
TI  - Astral microtubules are not required for anaphase B in Saccharomyces cerevisiae.
AB  - tub2-401 is a cold-sensitive allele of TUB2, the sole gene encoding beta-tubulin
      in the yeast, Saccharomyces cerevisiae. At 18 degrees C, tub2-401 cells are able
      to assemble spindle microtubules but lack astral microtubules. Under these
      conditions, movement of the spindle to the bud neck is blocked. However, spindle
      elongation and chromosome separation are unimpeded and occur entirely within the
      mother cell. Subsequent cytokinesis produces one cell with two nuclei and one
      cell without a nucleus. The anucleate daughter can not bud. The binucleate
      daughter proceeds through another cell cycle to produce a cell with four nuclei
      and another anucleate cell. With additional time in the cold, the number of
      nuclei in the nucleated cells continues to increase and the percentage of
      anucleate cells in the population rises. The results indicate that astral
      microtubules are needed to position the spindle in the bud neck but are not
      required for spindle elongation at anaphase B. In addition, cell cycle
      progression does not depend on the location or orientation of the spindle.

PMID- 1400582
TI  - Kinesin is bound with high affinity to squid axon organelles that move to the
      plus-end of microtubules.
AB  - This paper addresses the question of whether microtubule-directed transport of
      vesicular organelles depends on the presence of a pool of cytosolic factors,
      including soluble motor proteins and accessory factors. Earlier studies with
      squid axon organelles (Schroer et al., 1988) suggested that the presence of
      cytosol induces a > 20-fold increase in the number of organelles moving per unit
      time on microtubules in vitro. These earlier studies, however, did not consider
      that cytosol might nonspecifically increase the numbers of moving organelles,
      i.e., by blocking adsorption of organelles to the coverglass. Here we report that
      treatment of the coverglass with casein, in the absence of cytosol, blocks
      adsorption of organelles to the coverglass and results in vigorous movement of
      vesicular organelles in the complete absence of soluble proteins. This technical
      improvement makes it possible, for the first time, to perform quantitative
      studies of organelle movement in the absence of cytosol. These new studies show
      that organelle movement activity (numbers of moving organelles/min/micron
      microtubule) of unextracted organelles is not increased by cytosol. Unextracted
      organelles move in single directions, approximately two thirds toward the plus
      end and one third toward the minus-end of microtubules. Extraction of organelles
      with 600 mM KI completely inhibits minus-end, but not plus-end directed organelle
      movement. Upon addition of cytosol, minus-end directed movement of KI organelles
      is restored, while plus--end directed movement is unaffected. Biochemical studies
      indicate that KI-extracted organelles attach to microtubules in the presence of
      AMP-PNP and copurify with tightly bound kinesin. The bound kinesin is not
      extracted from organelles by 1 M KI, 1 M NaCl or carbonate (pH 11.3). These
      results suggest that kinesin is irreversibly bound to organelles that move to the
      plus-end of microtubules and that the presence of soluble kinesin and accessory
      factors is not required for movement of plus-end organelles in squid axons.

PMID- 1400583
TI  - Lysine residues form an integral component of a novel NH2-terminal membrane
      targeting motif for myristylated pp60v-src.
AB  - Association of pp60v-src with the plasma membrane is fundamental to generation of
      the transformed phenotype. Although myristylation of pp60v-src is required for
      interaction with a membrane-bound receptor, the importance of NH2-terminal amino
      acids in receptor binding has not yet been uncoupled from their role in signaling
      myristylation. Using chimeric src proteins, peptides identical or related to the
      NH2 terminus of src, and site-directed mutagenesis, we demonstrate that NH2
      terminal lysines in conjunction with myristate are essential for membrane
      localization. Subsequent to NH2-terminal interaction with the "src receptor,"
      internal regions of the src protein also participate in membrane binding. This
      novel NH2-terminal motif and internal contact mechanism may direct other members
      of the src family of tyrosine kinases to their membrane receptors.

PMID- 1400584
TI  - Suppression of tumorigenicity in transformed cells after transfection with
      vinculin cDNA.
AB  - Transfection of chicken vinculin cDNA into two tumor cell lines expressing
      diminished levels of the endogenous protein, brought about a drastic suppression
      of their tumorigenic ability. The SV-40-transformed Balb/c 3T3 line (SVT2)
      contains four times less vinculin than the parental 3T3 cells, and the rat
      adenocarcinoma BSp73ASML has no detectable vinculin. Restoration of vinculin in
      these cells, up to the levels found in 3T3 cells, resulted in an apparent
      increase in substrate adhesiveness, a decrease in the ability to grow in soft
      agar, and suppression of their capacity to develop tumors after injection into
      syngeneic hosts or nude mice. These results suggest that vinculin, a cytoplasmic
      component of cell-matrix and cell-cell adhesions, may have a major suppressive
      effect on the transformed phenotype.

PMID- 1400585
TI  - Glycosyl phosphatidylinositol--anchored T-cadherin mediates calcium-dependent,
      homophilic cell adhesion.
AB  - Cadherins are a family of cell adhesion molecules that exhibit calcium-dependent,
      homophilic binding. Their function depends on both an HisAlaVal sequence in the
      first extracellular domain, EC1, and the interaction of a conserved cytoplasmic
      region with intracellular proteins. T-cadherin is an unusual member of the
      cadherin family that lacks the HisAlaVal motif and is anchored to the membrane
      through a glycosyl phosphatidylinositol moiety (Ranscht, B., and M. T. Dours
      Zimmermann. 1991. Neuron. 7:391-402). To assay the function of T-cadherin in cell
      adhesion, we have transfected T-cadherin cDNA into CHO cells. Two proteins,
      mature T-cadherin and the uncleaved T-cadherin precursor, were produced from T
      cadherin cDNA. The T-cadherin proteins differed from classical cadherins in
      several aspects. First, the uncleaved T-cadherin precursor was expressed,
      together with mature T-cadherin, on the surface of the transfected cells. Second,
      in the absence of calcium, T-cadherin was more resistant to proteolytic cleavage
      than other cadherins. Lastly, in contrast to classical cadherins, T-cadherin was
      not concentrated into cell-cell contacts between transfected cells in monolayer
      cultures. In cellular aggregation assays, T-cadherin induced calcium-dependent,
      homophilic adhesion which was abolished by treatment of T-cadherin-transfected
      cells with phosphatidylinositol-specific phospholipase C. These results
      demonstrate that T-cadherin is a functional cadherin that differs in several
      properties from classical cadherins. The function of T-cadherin in homophilic
      cell recognition implies that the mechanism of T-cadherin-induced adhesion is
      distinct from that of classical cadherins.

PMID- 1400587
TI  - Identification of programmed cell death in situ via specific labeling of nuclear
      DNA fragmentation.
AB  - Programmed cell death (PCD) plays a key role in developmental biology and in
      maintenance of the steady state in continuously renewing tissues. Currently, its
      existence is inferred mainly from gel electrophoresis of a pooled DNA extract as
      PCD was shown to be associated with DNA fragmentation. Based on this observation,
      we describe here the development of a method for the in situ visualization of PCD
      at the single-cell level, while preserving tissue architecture. Conventional
      histological sections, pretreated with protease, were nick end labeled with
      biotinylated poly dU, introduced by terminal deoxy-transferase, and then stained
      using avidin-conjugated peroxidase. The reaction is specific, only nuclei located
      at positions where PCD is expected are stained. The initial screening includes:
      small and large intestine, epidermis, lymphoid tissues, ovary, and other organs.
      A detailed analysis revealed that the process is initiated at the nuclear
      periphery, it is relatively short (1-3 h from initiation to cell elimination) and
      that PCD appears in tissues in clusters. The extent of tissue-PCD revealed by
      this method is considerably greater than apoptosis detected by nuclear
      morphology, and thus opens the way for a variety of studies.

PMID- 1400586
TI  - Migrating endothelial cells are distinctly hyperglycosylated and express specific
      migration-associated cell surface glycoproteins.
AB  - Migration of endothelial cells is one of the first cellular responses in the
      cascade of events that leads to re-endothelialization of an injured vessel and
      neovascularization of growing tissues and tumors. To examine the hypothesis that
      endothelial cells express a specific migration-associated phenotype, we analyzed
      the cell surface glycoprotein expression of migrating bovine aortic endothelial
      cell (BAECs). Light microscopic analysis revealed an upregulation of binding
      sites for the lectins Concanavalin A (Con A), wheat germ agglutinin (WGA), and
      peanut agglutinin after neuraminidase treatment (N-PNA) on migrating endothelial
      cells relative to contact-inhibited cells. These findings were confirmed and
      quantitated with an enzyme-linked lectin assay (ELLA) of circularly scraped BAEC
      monolayers. The expression of migration-associated cell surface glycoproteins was
      also analyzed by SDS-PAGE. The overall expression of cell surface glycoproteins
      was upregulated on migrating BAECs. Migrating BAECs expressed Con A- and WGA
      binding glycoproteins with apparent molecular masses of 25 and 48 kD that were
      not expressed by contact-inhibited BAEC monolayers and, accordingly, disappeared
      as circularly scraped monolayers reached confluence. Subconfluent BAEC monolayers
      expressed the same cell surface glycoconjugate pattern as migrating endothelial
      cells. FACS analysis of circularly scraped BAEC monolayers showed that the
      phenotypic changes of cell surface glycoprotein expression after release from
      growth arrest occurred before the recruitment of the cells into the cell cycle (3
      vs. 12 h). Suramin, which inhibits endothelial cell migration, abrogated the
      expression of the migration-associated phenotype and induced the expression of a
      prominent 28-kD Con A- and WGA-binding cell surface glycoprotein. These results
      indicate that endothelial cells express a specific migration-associated
      phenotype, which is characterized by the upregulation of distinct cellular
      glycoconjugates and the expression of specific migration-associated cell surface
      glycoproteins.

PMID- 1400589
TI  - Amino- and carboxy-terminal deletion mutants of Gs alpha are localized to the
      particulate fraction of transfected COS cells.
AB  - To elucidate the structural basis for membrane attachment of the alpha subunit of
      the stimulatory G protein (Gs alpha), mutant Gs alpha cDNAs with deletions of
      amino acid residues in the amino and/or carboxy termini were transiently
      expressed in COS-7 cells. The particulate and soluble fractions prepared from
      these cells were analyzed by immunoblot using peptide specific antibodies to
      monitor distribution of the expressed proteins. Transfection of mutant forms of
      Gs alpha with either 26 amino terminal residues deleted (delta 3-28) or with 59
      amino terminal residues deleted (delta 1-59) resulted in immunoreactive proteins
      which localized primarily to the particulate fraction. Similarly, mutants with 10
      (delta 385-394), 32 (delta 353-384), or 42 (delta 353-394) amino acid residues
      deleted from the carboxy terminus also localized to the particulate fraction, as
      did a mutant form of Gs alpha lacking amino acid residues at both the amino and
      carboxy termini (delta 3-28)/(delta 353-384). Mutant and wild type forms of Gs
      alpha demonstrated a similar degree of tightness in their binding to membranes as
      demonstrated by treatment with 2.5 M NaCl or 6 M urea, but some mutant forms were
      relatively resistant compared with wild type Gs alpha to solubilization by 15 mM
      NaOH or 1% sodium cholate. We conclude that: (a) deletion of significant portions
      of the amino and/or carboxyl terminus of Gs alpha is still compatible with
      protein expression; (b) deletion of these regions is insufficient to cause
      cytosolic localization of the expressed protein. The basis of Gs alpha membrane
      targeting remains to be elucidated.

PMID- 1400588
TI  - SED5 encodes a 39-kD integral membrane protein required for vesicular transport
      between the ER and the Golgi complex.
AB  - The ERD2 gene, which encodes the yeast HDEL (His-Asp-Glu-Leu) receptor, is
      essential for growth (Semenza, J. C., K. G. Hardwick, N. Dean, and H. R. B.
      Pelham. 1990. Cell. 61:1349-1357; Lewis, M. J., D. J. Sweet, and H. R. B. Pelham.
      1990. Cell. 61:1359-1363). SED5, when present in multiple copies, enables cells
      to grow in the absence of Erd2p. Sequence analysis of SED5 reveals no significant
      homology with ERD2 or other known genes. We have raised antibodies to Sed5p which
      specifically recognize a 39-kD integral membrane protein. A stretch of
      hydrophobic residues at the COOH terminus is predicted to hold Sed5p on the
      cytoplasmic face of intracellular membranes. Cells that are depleted of Sed5p are
      unable to transport carboxypeptidase Y to the Golgi complex, and stop growing
      after a dramatic accumulation of ER membranes and vesicles. We conclude that the
      SED5 gene is essential for growth and that Sed5p is required for ER to Golgi
      transport. When Sed5p is overexpressed the efficiency of ER to Golgi transport is
      reduced, vesicles accumulate, and cellular morphology is perturbed.
      Immunofluorescence studies reveal that the bulk of Sed5p is not found on ER
      membranes but on punctate structures throughout the cytoplasm, the number of
      which increases upon SED5 overexpression. We suggest that Sed5p has an essential
      role in vesicular transport between ER and Golgi compartments and that it may
      itself cycle between these organelles.

PMID- 1400590
TI  - Class II MHC molecules are present in macrophage lysosomes and phagolysosomes
      that function in the phagocytic processing of Listeria monocytogenes for
      presentation to T cells.
AB  - Phagocytic processing of heat-killed Listeria monocytogenes by peritoneal
      macrophages resulted in degradation of these bacteria in phagolysosomal
      compartments and processing of bacterial antigens for presentation to T cells by
      class II MHC molecules. Within 20 min of uptake by macrophages, Listeria peptide
      antigens were expressed on surface class II MHC molecules, capable of stimulating
      Listeria-specific T cells. Within this period, degradation of labeled bacteria to
      acid-soluble low molecular weight catabolites also commenced. Immunoelectron
      microscopy was used to evaluate the compartments involved in this processing.
      Upon uptake of the bacteria, phagosomes containing Listeria fused rapidly with
      both lysosomes and endosomes. Class II MHC molecules were present in a tubulo
      vesicular lysosome compartment, which appeared to fuse with phagosomes, as well
      as in the resulting phagolysosomes containing internalized Listeria; these
      compartments were all positive for Lamp 1 and cathepsin D and lacked 46-kD
      mannose-6-phosphate receptors. In addition, class II MHC and Lamp 1 were co
      localized in vesicles of the trans Golgi reticulum, where they were segregated
      from 46-kD mannose-6-phosphate receptors. Vesicles containing both Listeria
      derived components and class II MHC molecules were also observed; some of these
      may represent vesicles recycling from phagolysosomes, potentially bearing
      processed immunogenic peptides complexed with class II MHC. These results support
      a central role for lysosomes and phagolysosomes in the processing of bacterial
      antigens for presentation to T cells. Tubulo-vesicular lysosomes appear to
      represent an important convergence of endocytic, phagocytic and biosynthetic
      pathways, where antigens may be processed to allow binding to class II MHC
      molecules and recycling to the cell surface.

PMID- 1400591
TI  - Confocal laser microscopy of dystrophin localization in guinea pig skeletal
      muscle fibers.
AB  - A confocal laser microscope was used to analyze the localization pattern of
      dystrophin along the sarcolemma in guinea pig skeletal muscle fibers. Hind leg
      muscles of the normal animals were freshly dissected and frozen for cryostat
      sections, which were then stained with a monoclonal antidystrophin antibody. In
      confocal laser microscopy, immunofluorescence staining in relatively thick
      sections could be sharply imaged in thin optical sections. When longitudinal and
      transverse sections of muscle fibers were examined, the immunostaining of
      dystrophin was seen as linearly aligned fluorescent dots or intermittent lines
      along the sarcolemma. In longitudinally cut muscle fibers, many fluorescent dots,
      but not all, corresponded to the sarcomere pattern, especially the I band.
      Sections cut tangential to the sarcolemma also showed a lattice-like pattern of
      longitudinal and transverse striations of fluorescent dots. Double staining for
      dystrophin and vinculin showed that the two proteins were not exactly
      colocalized. The end portions of muscle fibers were much more intensely stained
      with antidystrophin antibody than the central portions, following the contour of
      elaborate surface specializations at the myo-tendon junction. The staining
      pattern at the myo-tendon junction was also discontinuous. These confocal
      microscopic observations suggest that dystrophin may be localized in a
      nonuniform, discontinuous pattern along the sarcolemma and in some relationship
      with the underlying myofibrils.

PMID- 1400592
TI  - Identification and characterization of two huge protein components of the brush
      border cytoskeleton: evidence for a cellular isoform of titin.
AB  - Two extremely high molecular weight proteins were found to be components of the
      intestinal epithelial cell brush border cytoskeleton. The largest brush border
      protein, designated T-protein, migrated on SDS gels as a doublet of polypeptides
      with molecular weights similar to muscle titin T I and T II. The other large
      brush border protein, designated N-protein, was found to have a polypeptide
      molecular weight similar to muscle nebulin. In Western analysis, a polyclonal
      antibody raised against brush border T-protein reacted specifically with T
      protein in isolated brush borders and cross-reacted with titin in pectoralis and
      cardiac muscle samples. T-protein was distinguished from the muscle titins by an
      anti-cardiac titin mAb. A polyclonal antibody raised against N-protein was
      specific for N-protein in brush borders and cross-reacted with nothing in
      pectoralis muscle. Immunolocalization in cryosections of intestinal epithelia and
      SDS-PAGE analysis of fractionated brush borders revealed that both T-protein and
      N-protein are concentrated distinctly in the brush border terminal web region
      subjacent to the microvilli, but absent from the microvilli. EM of rotary
      replicated T-protein samples revealed many of the molecules to be long (912 +/-
      40 nm) and fibrous with a globular head on one end. In some of the molecules, the
      head domain appeared to be extended in a fibrous conformation yielding T-protein
      up to 1,700-nm long. The brush border N-protein was found as long polymers with a
      repeating structural unit of approximately 450 nm. Our findings indicate that
      brush border T-protein is a cellular isoform of titin and suggest that both T
      protein and N-protein play structural roles in the brush border terminal web.

PMID- 1400593
TI  - Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A
      in newt lung cell mitosis.
AB  - Microtubules in the mitotic spindles of newt lung cells were marked using local
      photoactivation of fluorescence. The movement of marked segments on kinetochore
      fibers was tracked by digital fluorescence microscopy in metaphase and anaphase
      and compared to the rate of chromosome movement. In metaphase, kinetochore
      oscillations toward and away from the poles were coupled to kinetochore fiber
      shortening and growth. Marked zones on the kinetochore microtubules, meanwhile,
      moved slowly polewards at a rate of approximately 0.5 micron/min, which
      identifies a slow polewards movement, or "flux," of kinetochore microtubules
      accompanied by depolymerization at the pole, as previously found in PtK2 cells
      (Mitchison, 1989b). Marks were never seen moving away from the pole, indicating
      that growth of the kinetochore microtubules occurs only at their kinetochore
      ends. In anaphase, marked zones on kinetochore microtubules also moved polewards,
      though at a rate slower than overall kinetochore-to-pole movement. Early in
      anaphase-A, microtubule depolymerization at kinetochores accounted on average for
      75% of the rate of chromosome-to-pole movement, and depolymerization at the pole
      accounted for 25%. When chromosome-to-pole movement slowed in late anaphase, the
      contribution of depolymerization at the kinetochores lessened, and flux became
      the dominant component in some cells. Over the whole course of anaphase-A,
      depolymerization at kinetochores accounted on average for 63% of kinetochore
      fiber shortening, and flux for 37%. In some anaphase cells up to 45% of
      shortening resulted from the action of flux. We conclude that kinetochore
      microtubules change length predominantly through polymerization and
      depolymerization at the kinetochores during both metaphase and anaphase as the
      kinetochores move away from and towards the poles. Depolymerization, though not
      polymerization, also occurs at the pole during metaphase and anaphase, so that
      flux contributes to polewards chromosome movements throughout mitosis. Poleward
      force production for chromosome movements is thus likely to be generated by at
      least two distinct molecular mechanisms.

PMID- 1400594
TI  - Role of astral microtubules and actin in spindle orientation and migration in the
      budding yeast, Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, before the onset of anaphase, the spindle
      apparatus is always positioned with one spindle pole at, or through, the neck
      between the mother cell and the growing bud. This spindle orientation enables
      proper chromosome segregation to occur during anaphase, allowing one replicated
      genome to be segregated into the bud and the other to remain in the mother cell.
      In this study, we synchronized a population of cells before the onset of anaphase
      such that > 90% of the cells in the population had spindles with the correct
      orientation, and then disrupted specific cytoskeletal elements using temperature
      sensitive mutations. Disruption of either the astral microtubules or actin
      function resulted in improper spindle orientation in approximately 40-50% of the
      cells. When cells with disrupted astral microtubules or actin function entered
      into anaphase, there was a 100-200-fold increase in the frequency of binucleated
      cell bodies. Thus, the maintenance of proper spindle orientation by these
      cytoskeletal elements was essential for proper chromosome segregation. These data
      are consistent with the model that proper spindle orientation is maintained by
      directly or indirectly tethering the astral microtubules to the actin
      cytoskeleton. After nuclear migration, but before anaphase, bulk chromosome
      movement occurs within the nucleus apparently because the chromosomes are
      attached to a mobile spindle. The frequency and magnitude of bulk chromosome
      movement is greatly diminished by disruption of the astral microtubules but not
      by disruption of the nonkinetochore spindle microtubules. These results suggest
      that astral microtubules are not only important for spindle orientation before
      anaphase, but they also mediate force on the spindle, generating spindle
      displacement and in turn chromosome movement. Potential roles for this force in
      spindle assembly and orientation are discussed.

PMID- 1400597
TI  - Microsurgery.

PMID- 1400596
TI  - Finger and hand replantation. Surgical technique.
AB  - An approach to the technique of either finger, thumb, or hand replantation is
      presented in this article. Acceptable alternative approaches exist, but I have
      found those techniques described as practical and useful. Variations of these
      techniques will be necessary depending on any number of circumstances, but these
      considerations should be individualized to the specific patient and injury
      pattern.

PMID- 1400595
TI  - Requirement for VLA-4 and VLA-5 integrins in lymphoma cells binding to and
      migration beneath stromal cells in culture.
AB  - Physical interaction between human lymphomas and murine bone marrow derived
      stromal cells were studied. Nalm-6 pre-B cells adhered to BMS2 stromal cells and
      subsequently migrated beneath them, while Ramos Burkitt lymphoma cells, adhered
      but did not migrate. Four mAbs were established against Nalm-6 cells, which were
      able to block initial adhesion of Nalm-6 cells. Two of them were directed against
      the alpha 4 chain of VLA-4, and other two recognized the beta 1 chain of VLA
      integrins. Therefore, the initial adhesion of Ramos and Nalm-6 cells to BMS2 was
      largely mediated by the VLA-4 integrin expressed on lymphocytes. The
      corresponding ligand on stromal cells appears to be VCAM-1, because antibodies
      against murine VCAM-1 blocked the adhesion. However, antibodies against the alpha
      chain of VLA-4 were not capable of blocking subsequent migration beneath stromal
      cells. In contrast, antibodies against the beta chain of VLA integrins blocked
      the migration beneath stromal cells as well as the initial adhesion. Because a
      common beta chain can be shared among integrins, the role of other VLA integrins
      in Nalm-6 cells migration was investigated. VLA-5 and VLA-6 as well as VLA-4 were
      expressed on Nalm-6 cells, but not on Ramos cells. Additional blocking
      experiments revealed that VLA-4 and VLA-5 are likely to work in concert to
      mediate the migration of Nalm-6 cells beneath stromal cells. Thus, particular VLA
      integrins appear to be responsible not only for lymphocyte adhesion but also for
      migration with respect to stromal cells. These findings may have implications for
      cell-cell interactions and directed migration of lymphocytes in bone marrow and
      other tissues.

PMID- 1400598
TI  - Polydigit replantation.
AB  - A comparison of two fundamentally different techniques of multiple digit
      replantation is studied: a digit-by-digit versus structure-by-structure method.
      We conclude from this review that the structure-by-structure method is
      advantageous in terms of the shorter duration of the surgical procedure and
      possibly in terms of the survival rate of the replanted digits.

PMID- 1400599
TI  - Replantation proximal to the wrist.
AB  - Technical aspects of importance in replantation proximal to the wrist are
      somewhat different from those involved with digital replantation. Re-establishing
      blood flow rapidly by insertion of an arterial shunt, meticulous debridement,
      stable internal fixation of fractures, fasciotomy, and re-examination of the
      tissue 48 to 72 hours after replantation are discussed. Indications and
      contraindications for replantation in addition to maximizing use of "spare parts"
      are illustrated.

PMID- 1400600
TI  - Management of acute and chronic vascular injuries to the arm and forearm.
      Indications and technique.
AB  - Acute arterial injuries of the upper extremity account for half of civilian
      arterial injuries in the United States. The great majority of these injuries are
      due to penetrating trauma, with stab wounds and gunshot wounds being the most
      common cause. The history of the injury and a careful physical examination will
      identify most injuries. Arteriography should be performed when a vascular injury
      is suspected but not confirmed by physical examination. Reconstruction of
      critical vascular lesions is essential for restoration of flow distally.
      Noncritical lesions may be repaired in most cases, with long-term patency rates
      averaging 50% to 68%. Although amputation is uncommon after upper-extremity
      vascular injury, long-term disability can be significant in those patients with
      concomitant nerve injury. Chronic upper-extremity ischemia may be secondary to
      atherosclerotic occlusive disease, aneurysms, or arteriovenous fistulas.
      Angiography will delineate the diseased or occluded arterial segment, allowing
      bypass to be successful in more than 90% of cases. With careful attention to
      proper diagnosis and treatment, good to excellent long-term relief of symptoms
      can be obtained.

PMID- 1400601
TI  - Neurosensory free flaps to the hand. Indications and donor selection.
AB  - When used in properly selected cases, a neurosensory free flap provides
      sensibility, vascularity, and soft-tissue coverage to an injured hand.
      Appropriate selection of donor flaps based on the need for fine discriminatory or
      protective sensation is important for optimal results. Because of its thin,
      glabrous skin and a constant vascular and neural anatomy, the first web-space
      flap of the foot or its variants provide the best reconstructive choice for
      restoration of critical sensibility to digital tips or anesthetic amputation
      stumps. Protective sensibility can be restored with other neurosensory free
      flaps, but more clinical experience is needed to fully evaluate the
      reconstructive potential of many described flaps. A distinction must be made
      between the anatomic description of a free flap with neurosensory potential and
      the report of long-term sensory ability after clinical transfer.

PMID- 1400602
TI  - Indications for free soft-tissue flap transfer to the upper limb and the role of
      alternative procedures.
AB  - The aim of soft-tissue replacement to the upper limb is twofold. The first is to
      restore as much functional tissue as possible, and the second is to achieve this
      in the shortest possible time. Of lesser consideration is the desire to achieve a
      good cosmetic result. In any given clinical situation, no single reconstructive
      procedure will maximally satisfy these aims. The personal philosophy expounded in
      this article exposes disadvantages as well as advantages of the many operations
      available to the upper limb surgeon. Each clinical problem is different from any
      other, so no blueprint or computer program is available to help the surgeon
      select an operation. It takes judgment based on knowledge and experience on the
      part of the surgeon to make the most appropriate selection. During the last two
      decades, free vascularized transfers have superseded some of the conventional
      pedicled flap operations, and this has been acclaimed quite rightly as a
      significant advance. By the same token, indications for the "older" techniques
      should remain in the armamentarium of the surgeon because in certain situations
      these may yet offer the best solution. A spin-off of the microsurgical era is the
      reverse forearm island flap, and in my view, this has become a new "star" in the
      recent era. It is fitting that it should have prominence in the reconstructive
      arena because it straddles the border between microsurgical and nonmicrosurgical
      techniques. It is a modern reminder that there are many ways to treat defects of
      the upper limb and that the responsibility of the surgeon is to be both
      imaginative and wise in securing the best possible result for the patient.

PMID- 1400603
TI  - Vascularized bone grafts to the upper extremity. Indications and technique.
AB  - Massive autogenous bone grafts with an intact vascular pedicle decrease the time
      to bony union and immobilization required for treatment of segmental bony
      defects. These techniques have been shown to be effective in treatment of
      segmental defects of more than 6 cm after trauma or tumor resection in relatively
      avascular beds. Additionally, in the upper extremity, the free vascularized bone
      graft is in the developmental phase for employment in the reconstruction of
      epiphyseal arrest and congenital radial club hand. There are disadvantages to
      free vascularized bone transfers compared with conventional techniques. For
      example, a free vascularized fibular transfer requires a team skilled in
      microvascular technique, a long operative time (6 to 10 hours), and the sacrifice
      of a major vessel to the lower extremity. If the anastomosis fails, however, the
      free vascularized fibula will act as a conventional bone graft, thereby
      minimizing adverse effects. We think that by proper patient selection,
      appropriate evaluation and preparation of the bony defect, meticulous
      microvascular anastomosis, and correct fixation and immobilization of the graft a
      good outcome can be achieved in those patients with large bony defects that defy
      the use of conventional methods.

PMID- 1400605
TI  - Thumb and fingertip reconstruction by composite microvascular tissue from the
      toes.
AB  - Toe-pulp web flaps have the potential to almost replicate the missing tissues
      resulting from defects of the thumb and fingers. The possibility of short- and
      long-term donor site morbidity and the technical demands of these transfers limit
      their use mainly to largish defects on the dominant sensory aspects of the radial
      digits. This limitation is especially true of the thumb, where a large volume of
      tissue is usually required. The toenail can be included or transferred alone. A
      logical extension of these pulp and nail flaps is the wrap-around procedure for
      total thumb amputations at or distal to the metacarpophalangeal joint. In this
      procedure, a sleeve of skin, pulp, and nail is wrapped around an iliac crest bone
      graft to create an almost exact size match of the missing thumb while preserving
      all of the toes. Palmar or first-web defects in the hand do not need specialized
      skin replacement for function, and foot flaps are rarely indicated in these
      sites.

PMID- 1400604
TI  - Vascularized joint transfers. Indications and results.
AB  - Vascularized joint transfer can be beneficial in restoring joint function and
      maintaining growth. It is sometimes indicated in patients with painful post
      traumatic arthritis, post-traumatic joint instability, and post-traumatic
      deformity. The best indication for this procedure is in children whose joint
      injury is associated with damage to growth plates in any of the digits; however,
      the complications associated with this procedure should not be overlooked.
      Extensor lag is common. This complication may be prevented during the surgical
      procedure by using a step-cut osteotomy to preserve the insertion of the extensor
      tendon, resecting the volar plate of the finger, harvesting the transferred joint
      with enough length to keep the extensor tendon tight, and placing the transferred
      joint in a maximally extended position to counteract the flexible trend of the
      toe joints. We believe this procedure holds promise for the future. Further
      improvement in surgical technique and clarification of its indications will
      likely enhance overall results.

PMID- 1400606
TI  - Thumb and finger reconstruction by toe-to-hand transfer.
AB  - Toe transplantation provides a means of restoring a thumb or finger in a single
      microsurgical procedure with tissues anatomically similar to those lost or
      absent. Although formidable, these toe transplantation procedures can be
      accomplished by experienced teams of microsurgeons with a high rate of success.

PMID- 1400607
TI  - Primary nerve repair in the upper limb. Our preferred methods: theory and
      practical applications.
AB  - After years of controversy, it is now generally agreed that primary nerve repair
      by end-to-end coaptation, whenever feasible, yields better results than secondary
      procedures. We reviewed the theoretic basis of current methods of repair and
      described our preferred techniques and indications.

PMID- 1400608
TI  - Secondary nerve reconstruction.
AB  - Presented is a review of nerve grafting, including the indications, technique,
      and results. Alternative techniques, including vascularized nerve grafts,
      tubulization, nerve elongation, and direct muscle neurotization are also
      discussed.

PMID- 1400609
TI  - Defective insulin secretion in NIDDM: integral part of a multiplier hypothesis.
AB  - Non-insulin dependent diabetes mellitus (NIDDM) is characterized by a specific
      defect in glucose recognition by the pancreatic islet beta cell. This is in clear
      distinction to patients with insulin dependent diabetes mellitus (IDDM) who
      undergo pancreatic islet beta cell death and no longer have the ability to
      synthesize, store, and release insulin. Defective glucose-induced first phase
      insulin responses in patients with NIDDM can be partially restored by exogenous
      insulin treatment and by other pharmacologic therapy. These observations provide
      strength for the theory of glucose desensitization of the pancreatic beta cell as
      an important secondary defect in the pathogenesis of abnormal insulin secretion
      in NIDDM. However, even though defective insulin secretion is an essential part
      of the pathogenesis of NIDDM, in itself it is not sufficient. A multiplicative
      effect is required involving interaction between tissue resistance to insulin
      action and defective insulin secretion whose product is the syndrome of NIDDM.

PMID- 1400610
TI  - Rapid induction of competence formation is PDGF-isoform specific.
AB  - Platelet-derived growth factor (PDGF) stimulates the expression of a number of
      genes associated with entry of quiescent Balb/c-3T3 fibroblasts into the cell
      cycle. We determined that two of these genes, c-myc and c-fos, are induced
      equivalently in medium supplemented with platelet-poor plasma (PPP) and either
      PDGF-BB or PDGF-AA. The rate at which fibroblasts entered S phase was also
      similar in PDGF-BB- and AA-treated cells as was the expression of the late G1
      gene, thymidine kinase (TK). However, PDGF-AA must be present for a period of 16
      h to stimulate the proliferation of 90% of the cells, whereas PDGF-BB was
      required for only 4 h. Exposure of cells to PDGF-AA for 4 h, a time during which
      maximum expression of c-fos and c-myc occurred, only induced 20% of the cells in
      a quiescent population to enter the cell cycle. Therefore, PDGF-AA-mediated
      expression of the immediate early genes c-fos and c-myc may be necessary but is
      not sufficient to rapidly stimulate density-arrested Balb/c-3T3 fibroblasts into
      the competent state. Thus, these data suggest that PDGF-AA and PDGF-BB initiate
      traverse of the cell cycle by distinct mechanisms.

PMID- 1400612
TI  - Protein kinase C activation amplifies prostaglandin F2 alpha-induced
      prostaglandin E2 synthesis in osteoblast-like cells.
AB  - In cloned osteoblast-like cells, MC3T3-E1, prostaglandin F2 alpha (PGF2 alpha)
      stimulated arachidonic acid (AA) release in a dose-dependent manner in the range
      between 1 nM and 10 microM. 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein
      kinase C (PKC) activator, which by itself had little effect on AA release,
      markedly amplified the release of AA stimulated by PGF2 alpha in a dose-dependent
      manner. 4 alpha-phorbol 12,13-didecanoate, a phorbol ester which is inactive for
      PKC, showed little effect on the PGF2 alpha-induced AA release. 1-oleoyl-2
      acetylglycerol (OAG), a specific activator for PKC, mimicked TPA by enhancement
      of the AA release induced by PGF2 alpha. H-7, a PKC inhibitor, markedly
      suppressed the effect of OAG on PGF2 alpha-induced AA release. Quinacrine, a
      phospholipase A2 inhibitor, showed partial inhibitory effect on PGF2 alpha
      induced AA release, while it suppressed the amplification by OAG of PGF2 alpha
      induced AA release almost to the control level. Furthermore, TPA enhanced the AA
      release induced by melittin, known as a phospholipase A2 activator. On the other
      hand, TPA inhibited the formation of inositol trisphosphate stimulated by PGF2
      alpha. Under the same condition, PGF2 alpha indeed stimulated prostaglandin E2
      (PGE2) synthesis and TPA markedly amplified the PGF2 alpha-induced PGE2 synthesis
      as well as AA release. These results indicate that the activation of PKC
      amplifies PGF2 alpha-induced both AA release and PGE2 synthesis through the
      potentiation of phospholipase A2 activity in osteoblast-like cells.

PMID- 1400611
TI  - Expression of the chicken hepatic glycoprotein receptor in Xenopus oocytes:
      conservation of ligand and receptor targeting signals.
AB  - We have obtained expression of the beta-N-acetylglucosamine-binding receptor from
      chicken hepatocytes in Xenopus oocytes by injecting mRNA synthesized in vitro
      from a full length cDNA cloned into an expression vector (Mellow et al: J. Biol
      Chem 263: 5468-5473, 1988). Immunoprecipitation of the receptor after labeling of
      oocytes with [35S]-methionine for times ranging from 6 to 72 h revealed 4-5
      closely spaced bands of 25-30 kDa after SDS-PAGE. Although these bands were
      largely resistant to endoglycosidase H cleavage, endoglycosidase F reduced the
      size of all bands to a single species at 23-24 kDa, indicating that they resulted
      from heterogeneity in glycosylation of a single polypeptide. Incubation of
      oocytes expressing this receptor with [125I]-GlcNAc-BSA resulted in 1.8 to 10 x
      higher levels of cell-associated ligand in mRNA-injected vs. water-injected
      control oocytes, 2-35% of cell-associated counts was removed by EGTA rinse at 20
      degrees C, suggesting that most ligand was inaccessible (presumably
      intracellular). Immunoprecipitation of sucrose gradient fractions detected
      receptor molecules predominantly in a light organelle at 1.09-1.12 g/cc (the
      density of early endosomes and plasma membrane vesicles), with no evidence of the
      receptor in much heavier yolk platelet fractions even in the presence of ligand.
      In contrast, internalized [125I]-GlcNAc-BSA was found either at the top of the
      gradients or in organelles at 1.09-1.17 g/cc and in yolk platelets. TCA
      precipitation indicated that much intracellular ligand was degraded to acid
      soluble fragments. Addition of vitellogenin (the yolk protein precursor) to the
      medium together with the [125I]-GlcNAc-BSA shifted much of the ligand into yolk
      platelets. These data indicate that the chicken glycoprotein receptor expressed
      in oocytes mediates binding and internalization of this ligand into an organelle
      in which ligand-receptor dissociation occurs, allowing for separation of these
      two molecules into different compartments. The behavior of ligand in Xenopus
      oocytes expressing the chicken receptor closely resembles its behavior in
      hepatocytes.

PMID- 1400613
TI  - Receptor binding of asialoerythropoietin.
AB  - The interaction of 125I-asialoerythropoietin (asialoepo) with receptors has been
      characterized both by binding assay and affinity cross-linking. Purified spleen
      cells from mice infected with the anemia strain of Friend virus (FVA cells) have
      receptors for 125I-asialoepo with two classes of affinity constant: one with Kd =
      0.02-0.03 nM and 300-400 per cell, the other with lower affinity (Kd = 0.9-1.2
      nM) and 1,000-1,200 per cell. The Kd value for the high affinity site is one
      third of that for the binding of native 125I-erythropoietin (125I-epo) to the
      same FVA cells (Kd = 0.08-0.1 nM). Using 125I-asialoepo or 125I-epo affinity
      cross-linking methods, we find two components with apparent molecular weights of
      88 kDa and 105 kDa in FVA cells, and in the transformed mouse cell lines, 201,
      IW32, and NN10, in agreement with earlier studies using 125I-epo. These results
      indicate that 125I-asialoepo binds to the same receptors as 125I-epo, but with
      greater affinity for the high affinity site. Since 201 cells contain only a
      single class of lower affinity receptors for erythropoietin (epo), finding the
      same two components as found for FVA cells by cross-linking experiment indicates
      that the two components do not represent the two classes of receptor.

PMID- 1400614
TI  - Expression of heat shock genes during differentiation of mammalian osteoblasts
      and promyelocytic leukemia cells.
AB  - The progressive differentiation of both normal rat osteoblasts and HL-60
      promyelocytic leukemia cells involves the sequential expression of specific genes
      encoding proteins that are characteristic of their respective developing cellular
      phenotypes. In addition to the selective expression of various phenotype marker
      genes, several members of the heat shock gene family exhibit differential
      expression throughout the developmental sequence of these two cell types. As
      determined by steady state mRNA levels, in both osteoblasts and HL-60 cells
      expression of hsp27, hsp60, hsp70, hsp89 alpha, and hsp89 beta may be associated
      with the modifications in gene expression and cellular architecture that occur
      during differentiation. In both differentiation systems, the expression of hsp27
      mRNA shows a 2.5-fold increase with the down-regulation of proliferation while
      hsp60 mRNA levels are maximal during active proliferation and subsequently
      decline post-proliferatively. mRNA expression of two members of the hsp90 family
      decreases with the shutdown of proliferation, with a parallel relationship
      between hsp89 alpha mRNA levels and proliferation in osteoblasts and a delay in
      down-regulation of hsp89 alpha mRNA levels in HL-60 cells and of hsp89 beta mRNA
      in both systems. Hsp70 mRNA rapidly increases, almost twofold, as proliferation
      decreases in HL-60 cells but during osteoblast growth and differentiation was
      only minimally detectable and showed no significant changes. Although the
      presence of the various hsp mRNA species is maintained at some level throughout
      the developmental sequence of both osteoblasts and HL-60 cells, changes in the
      extent to which the heat shock genes are expressed occur primarily in association
      with the decline of proliferative activity. The observed differences in patterns
      of expression for the various heat shock genes are consistent with involvement in
      mediating a series of regulatory events functionally related to the control of
      both cell growth and differentiation.

PMID- 1400615
TI  - TGF-beta 1 inhibits DNA synthesis and phosphorylation of the retinoblastoma gene
      product in a rat liver epithelial cell line.
AB  - In the rat liver epithelial cell line, WB, the ability of TGF-beta 1 to inhibit
      DNA synthesis was shown to correlate with its ability to inhibit phosphorylation
      of the protein product of the retinoblastoma susceptibility gene, pRb. When WB
      cells were serum-starved, then refed with serum-containing medium, a peak of DNA
      synthesis occurred at about 18 h. Autoradiographs showed that 43.6% of cell
      nuclei could be labeled with 3H-thymidine at this time. When TGF-beta 1 was added
      simultaneously with serum, it blocked DNA synthesis and reduced the number of
      labeled nucleii to 6.3%. Cells treated with serum alone for 18 h also showed a
      pronounced increase in the highly phosphorylated form of pRb, as shown by
      mobility shifts in immunoblots, and in active phosphorylation of pRb, as shown by
      32P incorporation. Simultaneous addition of TGF-beta 1 with serum abolished both
      32P incorporation into pRb and its mobility shift on immunoblots. The effect of
      TGF-beta 1 on DNA synthesis measured at 18 h was sharply reduced if the cells
      were incubated with serum for 8 h (and thus allowed to enter S) before the
      addition of TGF-beta 1. If TGF-beta 1 was added after 8 h of serum treatment, its
      ability to inhibit pRb phosphorylation at 18 h was unchanged. If TGF-beta 1 was
      added after 13 h of serum treatment, its effects on pRb phosphorylation were
      reduced. Thus, as the cell population moved into S, the ability of TGF-beta 1 to
      inhibit both pRb phosphorylation and DNA synthesis was lost. In higher passages
      of WB cells the dose-response for inhibition of DNA synthesis by TGF-beta 1 was
      shifted to the right. Inhibition of pRb phosphorylation by TGF-beta 1 was also
      lost in higher passage WB cells. Thus, the passage-dependent loss of sensitivity
      to inhibition of DNA synthesis accompanied the loss of sensitivity to inhibition
      of pRb phosphorylation. Since the phosphorylation of pRb is believed to be
      required for the progression of cells from G1 to S, inhibition of pRb
      phosphorylation may be either a cause or a consequence of the G1 arrest of WB
      cells by TGF-beta 1.

PMID- 1400617
TI  - Transgenic animals: "great and small".

PMID- 1400616
TI  - Biochemical and morphological differentiation of the human colonic epithelial
      cell line SW620 in the presence of dimethylsulfoxide.
AB  - In vitro models of intestinal cell differentiation provide an important adjunct
      for studying normal and abnormal intestinal epithelial cell differentiation. The
      studies reported herein describe morphologic and biochemical changes in the
      colonic epithelial cell line SW620 following dimethylsulfoxide (DMSO) incubation.
      Cells cultured in the presence of DMSO showed striking changes in morphology
      characterized by enlargement, elongation, and formation of process-like
      structures by light microscopy and a propensity to form microvillus-like
      structures by electron microscopy. These changes were accompanied by significant
      differences in the expression of the cell surface markers CD4 (HIV gp120
      receptor), CD44 (hyaluronate receptor), and KS1 (adenocarcinoma/epithelial
      specific antigen). There was a marked decrease in CD4 expression (38% to 2%), an
      increase in CD44 expression (4% to 50%) and a decrease in KS1 expression (98% to
      66%) as detected by flow cytometry following incubation of SW620 cells in DMSO.
      Parallel changes in the expression of these markers were seen by metabolic and
      surface labeling studies. Although SW620 cells were infected by HIV-1, DMSO
      treated SW620 cells could not be infected. DMSO-induced changes in surface
      expression of CD4, CD44, and KS-1 were reversible over time upon removal of DMSO
      from the culture medium. Secretory component, sucrase, neuron-specific enolase,
      chromogranin-A, and mucin were not detectable in SW620 cells with or without DMSO
      treatment. SW620 cells provide a useful model for studying specific biochemical
      and molecular events involved in intestinal epithelial cell differentiation and
      function.

PMID- 1400618
TI  - Making transgenic livestock: genetic engineering on a large scale.
AB  - The feasibility of introducing foreign genes into the genomes of cattle, goats,
      pigs, and sheep has only recently been demonstrated. Studies have thus far
      focused on improving growth efficiency or directing expression of pharmaceutical
      proteins to the mammary glands of these species. The general strategy for
      producing transgenic livestock and mice is similar. In addition to the obvious
      difference in scale between mice and livestock experiments, there are noteworthy
      obstacles that significantly reduce the efficiency of producing transgenic
      livestock. Low embryo viability, low transgene integration rates, and high animal
      costs contribute to project costs that can easily exceed hundreds of thousands of
      dollars. A better understanding of the mechanisms that govern transgene
      integration should lead to improved efficiencies. But, the full potential of the
      transgenic livestock system will not be fully realized until: 1) gene constructs
      can be designed that function in a reproducible, predictable manner; and 2) the
      genetic control of physiological processes are more clearly elucidated. Newly
      emerging approaches may resolve at least some of these issues within the next
      decade.

PMID- 1400619
TI  - Prospects for the genetic engineering of milk.
AB  - Milk and milk products comprise a substantial fraction of the protein intake of
      the industrialised West. The establishment of germline manipulation techniques in
      cows offers opportunities for directly manipulating milk composition to produce
      products with enhanced nutritional and processing properties. The major milk
      proteins are encoded by a small number of abundantly expressed single-copy genes
      and a number of possible manipulations are described. Milk proteins exhibit
      complex interactions with each other and with other constituents of milk. It
      will, therefore, be necessary to utilise model systems to evaluate the
      consequences of these proposed changes before embarking upon the costly and time
      consuming process of manipulating the bovine genome.

PMID- 1400620
TI  - Oncogene expression in mammary epithelial cells.
AB  - Mouse strains which develop tumors at a high incidence with characteristics very
      similar to human cancers have been derived over the last 8 years. The tumors are
      caused by defined genetic alterations in the mouse genome. Three areas of
      research have contributed to the derivation of these mouse strains: (1) Molecular
      analysis of human tumors has shown that distinct oncogenes and tumor suppressor
      genes are consistently involved in a high percentage of primary tumors. (2)
      Regulatory enhancer-promoter sequences have been identified which direct gene
      expression to specific target cells, preferentially mammary epithelial cells. (3)
      The introduction of recombinant DNA molecules into fertilized mouse eggs by
      microinjection and integration of the injected DNA into the genome of injected
      cells has given rise to mutant mouse strains with unique and defined genetic
      alterations. Studies with different promoter-oncogene combinations introduced
      into transgenic mouse strains have led to the following general conclusions: (1)
      Oncogenes expressed in mammary gland cells predispose transgenic mice to mammary
      tumors. (2) The oncogenic potential of individual oncogenes in mammary epithelial
      cells differs. (3) Oncogene expression initially often causes a preneoplastic
      state affecting growth and differentiation parameters of cells. (4) The
      expression of different oncogenes synergizes to reduce tumor latency. Synergism
      can also be observed with physiological growth signals like estrogen or growth
      hormone. The oncogenes with a role in mammary carcinomas which have been
      investigated in transgenic mice will be described here. The phenotypic
      consequences of oncogene expression and the implications for the multistep
      carcinogenesis model will be discussed.

PMID- 1400622
TI  - A new monoclonal antibody for detection of EGF-receptors in western blots and
      paraffin-embedded tissue sections.
AB  - The prognostic significance of the epidermal growth factor receptor status (EGF-R
      status) for certain human tumors requires the development of antibodies useful
      for clinical application. We used purified receptor preparations to generate
      monoclonal antibodies immunoreactive with the EGF-R purified from placenta
      membranes and A431 tumors. Four of the hybridomas contained antibodies (R2, R3,
      R5, and R9) which recognized both antigens. Antibody R3 was shown to display the
      following properties: it binds with a KD value of about 10(-9)-10(-10) M to the
      receptor, a half maximal inhibition of EGF-binding is achieved at 5 x 10(-8) M,
      and in Western blots of cell membranes R3 specifically detects the EGF-R at 0.1
      micrograms/ml. R3 inhibits EGF-dependent clonogenic growth of NRK cells and
      completely blocks EGF stimulated autophosphorylation of the receptor. Moreover,
      R3 also detects EGF-R in paraffin-embedded tissue sections taken from human
      salivary gland, term placenta, and adult skin and mammary carcinomas. Thus, R3
      can be used in retrospective diagnostic clinical studies and might help to
      develop new immunotherapeutic intervention.

PMID- 1400621
TI  - Downregulation of histone H4 gene transcription during postnatal development in
      transgenic mice and at the onset of differentiation in transgenically derived
      calvarial osteoblast cultures.
AB  - In vivo regulation of cell cycle dependent human histone gene expression was
      examined in transgenic mice using a fusion construct containing 6.5 kB of a human
      H4 promoter linked to the chloramphenicol acetyltransferase (CAT) reporter gene.
      Transcriptional control of histone gene expression, as a function of
      proliferative activity, was determined. We established the relationship between
      DNA replication dependent H4 mRNA levels (Northern blot analysis) and H4 promoter
      activity (CAT assay) during postnatal development in a broad spectrum of tissues.
      In most tissues sampled in adult animals, the cellular representation of H4 gene
      transcripts declined in parallel with promoter activity. This result is
      consistent with transcriptional control of H4 gene expression at the cessation of
      proliferation. Interestingly, while H4 mRNA was detectable at very low levels
      post-proliferatively in brain, promoter activity persisted in adult brain, where
      most of the cells are terminally differentiated. This dissociation between
      histone gene promoter activity and histone mRNA accumulation points to the
      possibility of post-transcriptional regulation of histone gene expression in
      brain. Cultures of osteoblasts were prepared from calvaria of transgenic mice
      carrying the H4 promoter/CAT reporter construct. In contrast to the brain, in
      these bone-derived cells, we established by immunohistochemistry that the
      transition to the quiescent, differentiated state is associated with a
      transcriptionally mediated downregulation of histone gene expression at the
      single cell level.

PMID- 1400623
TI  - Extraction and partial characterization of non-histone nuclear proteins of
      Schistosoma mansoni.
AB  - A pool of nuclear proteins from adult worms of Schistosoma mansoni was analyzed
      for amino acid composition and found to be compatible with high mobility group
      (HMG) proteins. One of the schistosome HMG proteins was identified as HMG 2 by
      one-dimensional and two-dimensional PAGE. Stage-specific differences in the HMG
      like protein composition were encountered when adult worms were compared to
      schistosomula, the larval form. Immobilization of the adult male and female
      nuclear proteins onto nitrocellulose, followed by hybridization against 32P-F-10,
      a schistosome sex specific gene encoding a major egg shell protein, revealed
      distinct banding patterns. On the other hand, a synthetic oligonucleotide,
      derived from the 3' untranslated end of the F-10 gene and possibly containing one
      regulatory element of the gene, bound mainly to male low MW proteins.

PMID- 1400624
TI  - Modulation of cultured chicken growth plate chondrocytes by transforming growth
      factor-beta 1 and basic fibroblast growth factor.
AB  - Expression of several cellular and matrix proteins which increase significantly
      during the maturation of growth plate cartilage has been shown to be affected by
      various endocrine and autocrine factors. In the studies reported here,
      transforming growth factor-beta (TGF-beta 1) and basic fibroblast growth factor
      (bFGF) were administered to primary cultures of avian growth plate chondrocytes
      at pre- or post-confluent stages to study the interplay that occurs between these
      factors in modulating chondrocytic phenotype. Added continuously to pre-confluent
      chondrocytes, TGF-beta 1 stimulated the cells to produce abundant extracellular
      matrix and multilayered cell growth; cell morphology was altered to a more
      spherical configuration. These effects were generally mimicked by bFGF, but cell
      shape was not affected. Administered together with TGF-beta 1, bFGF caused
      additive stimulation of protein synthesis, and alkaline phosphatase (AP) activity
      was markedly, but transiently enhanced. During this pre-confluent stage, TGF-beta
      1 also increased fibronectin secretion into the culture medium. Added to post
      confluent cells, TGF-beta 1 alone caused a dosage-dependent suppression of AP
      activity, but bFGF alone did not. Under these conditions, TGF-beta 1 and bFGF had
      little effect on general protein synthesis, but TGF-beta 1 alone caused large,
      dosage-dependent increases in synthesis of fibronectin, and to some extent type
      II and X collagens. Given together with bFGF, TGF-beta 1 synergistically
      increased secretion of fibronectin. These findings reveal that regulation of
      phenotypic expression in maturing growth plate chondrocytes involves complex
      interactions between growth factors that are determined by timing, level,
      continuity, and length of exposure.

PMID- 1400625
TI  - Inhibition of renal Na(+)-Pi cotransporter by mercuric chloride: role of
      sulfhydryl groups.
AB  - We studied the role of sulfhydryl groups in Na(+)-Pi cotransport across the renal
      brush border membrane (BBM), using HgCl2, an agent which penetrates membranes
      freely. HgCl2 inhibited the initial Na(+)-dependent 32Pi transport in a dose
      dependent manner (IC50 = 54 microM). Na(+)-independent transport was not
      affected. The inhibitory effect persisted under Na+ equilibrium-exchange
      conditions. Additionally, HgCl2 had no effect on the diffusional uptake of 22Na
      up to 1 min incubation. Exposure to HgCl2 had no effect on vesicle integrity as
      determined by osmotic shrinking experiments. BBM vesicle (BBMV) volume,
      determined by D-glucose equilibrium uptake, was not affected at low HgCl2
      concentrations, but decreased at higher concentrations (greater than 100 microM).
      Vesicle volumes, determined by flow cytometry, were not changed after exposure to
      HgCl2. Kinetic studies showed a reduction in the apparent Vmax for Pi transport
      from 1.40 +/- 0.13 to 0.75 +/- 0.19 nmoles/mg protein/5 sec, without a
      significant change in the apparent Km. In protection studies, dithiothreitol
      (DTT) completely protected against inhibition, but Pi, phosphonoformic acid
      (PFA), and Na+ gave no protection. The data suggest that sulfhydryl groups are
      essential for the function of Na(+)-Pi cotransporter of renal BBM.

PMID- 1400626
TI  - Wild-type murine p53 represses transcription from the murine c-myc promoter in a
      human glial cell line.
AB  - Here we analyzed the effect of the suppressor proto-oncogene p53 on transcription
      from the P2 promoter of the murine c-myc gene. c-myc promoter constructs were
      coupled to the chloramphenicol acetyl-transferase (CAT) gene and were transiently
      transfected into a human glial cell along with plasmids overexpressing wild-type
      or mutant p53. It was found that significant repression of c-myc transcription
      took place following cotransfection with wild-type but not mutant p53. However
      wild-type p53 did not suppress transcription from the SV40 early promoter or from
      the MHC promoter. Promoter-CAT constructs containing only the ME1a2 or E2F
      elements, from the P2 promoter, were repressed by p53, indicating that p53 may
      exert its effect at these two sites within the P2 promoter. Finally, when the
      SV40 T antigen and wild-type p53 were expressed together in glial cells the
      repressive effect of p53 was abolished.

PMID- 1400627
TI  - Establishing and maintaining epithelial cell polarity. Roles of protein sorting,
      delivery and retention.

PMID- 1400628
TI  - Drosocrystallin, a major 52 kDa glycoprotein of the Drosophila melanogaster
      corneal lens. Purification, biochemical characterization, and subcellular
      localization.
AB  - We have identified a 52 kDa protein, which is a potent substrate for cholera
      toxin-dependent ADP-ribosylation, in the compound eye preparation of the fruit
      fly, Drosophila melanogaster. We find that the 52 kDa protein is a glycoprotein
      and a Ca2+ binder bearing a high content of leucine, serine and glycine. By
      microsequencing we determined its 13 N-terminal sequence, AYL*PIDLNQLAK, with the
      asterisk representing an ambiguous signal. In order to study further the 52 kDa
      protein we have raised a polyclonal antibody against a synthetic oligopeptide
      representing the N-terminal 13 residues of the 52 kDa protein. By immunogold
      labelling with the antibody, the epitopes were localized at the EM level to the
      laminated corneal lens. The number of the gold particles per microns2 in the
      electron-dense layer of the corneal lens was 2.5 times higher than that of the
      electron-lucent layer. The pattern of the 52 kDa protein distribution in the
      corneal lens suggests that the 52 kDa protein is the major protein component that
      participates in the pattern formation of the alternate refractive indices of the
      D. melanogaster corneal lens. An X-ray dispersion analysis in situ revealed that
      the laminated corneal lens contained a higher concentration of Ca2+, supporting
      the hypothesis that the 52 kDa protein binds Ca2+ in vivo. To the best of our
      knowledge, this is the first report that identifies the protein entity of an
      arthropod corneal lens. We propose to designate this 52 kDa protein
      drosocrystallin.

PMID- 1400629
TI  - A cell surface-associated centrosomal layer of microtubule-organizing material in
      the inner pillar cell of the mouse cochlea.
AB  - This investigation provides evidence that pericentriolar material is divorced
      from the immediate vicinities of centrioles and becomes functionally associated
      with the plasmalemma during the differentiation of a mammalian cell type. Such
      events occur prior to the assembly of large transcellular microtubule bundles in
      columnar epithelial cells called inner pillar cells in the mouse organ of Corti.
      The microtubules do not radiate from a typical centrosome and its centrioles.
      They elongate from a microtubule-organizing centre (MTOC), which is deployed as a
      subapical cell surface-associated layer in each cell. Most of the dense material
      of this layer, and the tops of most of the microtubules, are initially
      concentrated around the sides of a cell about 1 microns below its apical surface.
      In addition, a pair of centrioles is located above the layer, which acts as if it
      is a pericellular concentration of the pericentriolar material of a modified
      centrosome. Although microtubule nucleation takes place in a centrosome-like
      region, 13 protofilament fidelity is not exercised. Most of the microtubules have
      15 protofilaments. Microtubule assembly progresses in these cells after the organ
      of Corti has been isolated for in vitro culture. However, large numbers of
      microtubules elongate from pericentriolar material juxtaposed against the
      centrioles. Hence, there is some reversion by the centrosomes of cultured cells
      to the operational configuration regarded as typical for animal tissue cells in
      general.

PMID- 1400630
TI  - Expression of tau protein in non-neuronal cells: microtubule binding and
      stabilization.
AB  - The microtubule-associated protein tau is a developmentally regulated family of
      neuronal phosphoproteins that promotes the assembly and stabilization of
      microtubules. The carboxy-terminal half of the protein contains three copies of
      an imperfectly repeated sequence; this region has been found to bind microtubules
      in vitro. In addition, a fourth copy of the repeat has been found in adult
      specific forms of tau protein. To examine the structure and function of tau
      protein in vivo, we have transiently expressed fetal and adult forms of tau
      protein and tau protein fragments in tissue culture cells. Biochemical analysis
      reveals full-length products with heterogeneity in post-translational
      modification synthesized in the cells. Immunofluorescent staining of transfected
      cells shows that, under our conditions, sequences on both sides of the repeat
      region are required for in vivo microtubule co-localization. These additional
      regions may be required either for enhancing microtubule contacts or for proper
      protein folding in the cell. In our expression system, the bundling of cellular
      microtubules occurs only in transfections using four-repeat tau constructs; any
      four-repeat construct capable of binding is also able to induce bundling. Our
      data suggest that the presence of bundles is correlated with enhanced microtubule
      stability; factors that increase stability such as higher levels of tau protein
      expression or the presence of the fourth repeat, increase the fraction of
      transfected cells showing bundles. Finally, the presence of tau protein in the
      cell allows all interphase microtubules to become acetylated, a post
      translational modification usually reserved for a subset of stable cellular
      microtubules.

PMID- 1400631
TI  - Investigation of the role of microtubules in protein secretion from lactating
      mouse mammary epithelial cells.
AB  - Disruption of microtubules has been shown to reduce protein secretion from
      lactating mammary epithelial cells. To investigate the involvement of
      microtubules in the secretory pathway in these cells we have examined the effect
      of nocodazole on protein secretion from mammary epithelial cells derived from the
      lactating mouse. Mouse mammary cells have extensive microtubule networks and 85%
      of their tubulin was in a polymeric form. Treatment with 1 micrograms/ml
      nocodazole converted most of the tubulin into a soluble form. In a continuous
      labelling protocol it was found that nocodazole did not interfere with protein
      synthesis but over a 5 h period secretion was markedly inhibited. To determine
      whether the inhibition was at the level of early or late stages of the secretory
      pathway mammary cells were pulse-labelled for 1 h to label protein throughout the
      secretory pathway before nocodazole treatment. When secretion was subsequently
      assayed it was found to be slower and only partially inhibited. These findings
      suggest that the major effect of nocodazole is on an early stage of the secretory
      pathway and that microtubules normally facilitate vesicle transport to the plasma
      membrane. An involvement of microtubules in vesicle transport to the plasma
      membrane is consistent with an observed accumulation of casein vesicles in
      nocodazole-treated cells. Exocytosis stimulated by the calcium ionophore
      ionomycin was unaffected by nocodazole treatment. We conclude from these results
      that the major effect of nocodazole is at an early stage of the secretory
      pathway, one possible target being casein vesicle biogenesis in the trans-Golgi
      network.

PMID- 1400632
TI  - The flagellar beat of rat sperm is organized by the interaction of two
      functionally distinct populations of dynein bridges with a stable central
      axonemal partition.
AB  - Two distinct patterns of microtubular sliding were observed in rat sperm
      flagellar axonemes. The particular pattern of sliding was determined by the
      extraction conditions used to prepare the sperm for axoneme disintegration. Sperm
      prepared by incubating concentrated suspensions of Triton X-100-extracted sperm
      at pH 9.0 disintegrated by extruding the doublets and outer dense fibers numbered
      4 through 7 in response to Mg-ATP. Sperm prepared by incubating motile Triton X
      100-extracted models at 37 degrees C for 1 to 3 hours extruded doublets and outer
      dense fibers 9, 1 and 2. Axonemes disintegrated by both regimens tended to have
      doublets 3 and 8 (with their corresponding outer dense fibers), as well as the
      central pair, in place. In numerous instances, the 3-central-8 complex with outer
      dense fibers 3 and 8 could be found isolated in midpiece sections prepared from
      both methods. The 3-central-8 partition was also sometimes seen in isolation in
      cross-sections of the principal piece where it remained attached to the fibrous
      sheath. The flagellar remnant produced by extrusion of fibers 4 through 7 under
      high pH conditions was generally straight or randomly curved. In contrast, the
      flagellar remnant produced by extrusion of the 9-1-2 bundle of fibers was most
      often curved into a hook in the midpiece region. While the hook-like
      configuration was not Ca(2+)-dependent, it may be based on a related mechanism.
      The sliding of the 9-1-2 group of fibers is a consequence of dynein-tubulin
      sliding between the 2 and 3 doublets. This sliding pattern appears to be
      preferentially activated in the motile sperm models in EGTA, but seldom if ever
      produced sliding in the high-pH-extracted models. We conclude that the 3-central
      pair-8 complex and associated outer dense fibers form an I-beam-like partition
      that does not participate in sliding, but acts as a structural foundation for
      organizing a planar beat. In addition, it is clear that preferential activation
      of certain dynein arms can be evoked, depending on the treatment regimen
      employed. This shows definitively that the types of microtubule sliding in the
      two bend directions are not identical.

PMID- 1400633
TI  - Regulation of nuclear envelope precursor functions during cell division.
AB  - Previously, we have shown that nuclear envelope assembly in cell-free extracts of
      Xenopus eggs requires two distinct vesicle-containing fractions, called Nuclear
      Envelope Precursor Fractions A and B (NEP-A and NEP-B). These fractions are
      characterized further in this paper and the manner in which they are regulated
      during metaphase is examined. Antisera against the NEP-B fraction recognized
      several proteins common to NEP-B and Xenopus oocyte or liver nuclei, but not to
      NEP-A or cytosol. A known glycoprotein component of the nuclear pore complex,
      p62, also co-fractionated with NEP-B, whereas the Xenopus egg lamin LIII did not.
      Together, these results provide further evidence that the NEP-B fraction contains
      precursors of the nuclear envelope. The regulation of NEP-A and -B function
      during metaphase, when the nuclear envelope is disassembled, was examined by
      treating each fraction with metaphase cytosol or purified protein kinase
      preparations isolated from metaphase-arrested eggs. Treatment of NEP-B with
      metaphase cytosol, under conditions where proteins are irreversibly
      phosphorylated, inhibited the subsequent assembly of the nuclear envelope by
      preventing the binding of NEP-B to chromatin. In contrast, similar treatment of
      NEP-A did not affect its ability to form nuclear envelopes. The changes in NEP-B
      during metaphase did not appear to be regulated directly by either p34cdc2/cyclin
      B, S6 kinase II or MAP kinase.

PMID- 1400634
TI  - Distribution of a nuclear envelope antigen during the syncytial mitoses of the
      early Drosophila embryo as revealed by laser scanning confocal microscopy.
AB  - The changing distribution of a nuclear envelope antigen recognized by a
      monoclonal antibody raised against human fibroblast vimentin during the syncytial
      mitoses of the Drosophila embryo has been studied with a confocal laser scanning
      microscope. The antigen appears very early as irregular aggregates in the
      peripheral cytoplasm of the preblastoderm embryo. As the first nuclei reach the
      periplasm the antigen is localized on the nuclear envelope and the cytoplasmic
      staining decreases. In addition to the perinuclear labeling we observed intense
      midzone and polar staining during the mitotic cycle. A possible relationship
      between polar localization of the antigen and centrosome position is discussed.

PMID- 1400635
TI  - Regulation of fibroblast-mediated collagen gel contraction by platelet-derived
      growth factor, interleukin-1 alpha and transforming growth factor-beta 1.
AB  - We have examined the effects of three macrophage-derived cytokines, platelet
      derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-beta 1) and
      interleukin-1 alpha (IL-1 alpha) on the contraction of collagen type I gels
      populated by human foreskin fibroblasts. Contraction was quantified as loss in
      gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel
      contraction. TGF-beta 1 also stimulated gel contraction but with a delayed onset
      and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs
      recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects
      of the corresponding PDGF isoforms. However, the stimulatory effect of TGF-beta 1
      was not affected by any of the anti-PDGF antibodies. The ability of PDGF to
      stimulate contraction became less pronounced in collagen gel cultures grown in
      the absence of growth factors over periods of several days. Under the same
      conditions, the stimulatory effect of TGF-beta 1 was not reduced. The reduced
      response to PDGF may be due to reduced tension on fibroblasts growing in collagen
      gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF
      BB-induced PDGF beta-receptor aggregates when compared to fibroblasts on attached
      collagen gels. IL-1 alpha inhibited initial collagen gel contraction, and at
      later stages induced a visible degradation of the collagen gels, presumably due
      to the generation of collagenase activity. The combination of IL-1 alpha and PDGF
      BB stimulated initial collagen gel contraction, although less effectively than
      PDGF-BB alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400636
TI  - Evidence for an inverse relationship between the differentiation of adipocytic
      and osteogenic cells in rat marrow stromal cell cultures.
AB  - The differentiation of adipocytic and osteogenic cells has been investigated in
      cultures of adult rat marrow stromal cells. Adipocytic differentiation was
      assessed using morphological criteria, changes in expression of procollagen
      mRNAs, consistent with a switch from the synthesis of predominantly fibrillar
      (types I and III) to basement membrane (type IV) collagen, and the induction of
      expression of aP2, a specific marker for differentiation of adipocytes.
      Osteogenic differentiation was assessed on the basis of changes in the abundance
      of the mRNAs for the bone/liver/kidney isozyme of alkaline phosphatase and the
      induction of mRNAs for bone sialoprotein and osteocalcin. In the presence of
      foetal calf serum and dexamethasone (10(-8) M) there was always differentiation
      of both adipocytic and osteogenic cells. When the steroid was present throughout
      primary and secondary culture the differentiation of osteogenic cells
      predominated. Conversely, when dexamethasone was present in secondary culture
      only, the differentiation of adipocytes predominated. When marrow stromal cells
      were cultured in the presence of dexamethasone in primary culture and
      dexamethasone and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; 10(-8) M) in secondary
      culture, the differentiation of adipocytes was inhibited whereas the
      differentiation of osteogenic cells was enhanced, as assessed by an increase in
      expression of osteocalcin mRNA. The results, therefore, demonstrate an inverse
      relationship between the differentiation of adipocytic and osteogenic cells in
      this culture system and are consistent with the possibility that the regulation
      of adipogenesis and osteogenesis can occur at the level of a common precursor in
      vivo.

PMID- 1400637
TI  - Differential lectin binding to presumptive cortical cells of the wool follicle
      bulb.
AB  - An alpha-D-galactoside-specific lectin from Bandeiraea simplicifolia (BSLI)
      showed differential binding to cortical cells of the wool follicle bulb. The
      lectin bound to cells on one side only of the bulb and was completely blocked by
      alpha-D-galactose. The region of lectin binding extended from presumptive
      cortical cells at the base of the bulb to cortical cells at the top of the bulb,
      disappearing as cortical cells entered the fibre cortex. An orthocortex-specific
      monoclonal antibody was used to show that cortical cells recognised by the lectin
      lie directly below the fibre orthocortex and presumably give rise to the
      orthocortex. The results suggest that two distinct populations of presumptive
      cortical cells are present only two to three cell layers from the base of the
      bulb in a region where no morphological differences are detectable. The lectin
      bound pre-cortical cells appear to give rise to orthocortical cells while cells
      not bound by lectin presumably give rise to paracortical cells. Electron
      microscopy showed that the lectin bound to sites on the plasma membrane, probably
      on the extracellular surface. This suggests that the lectin target may be a
      membrane glycoprotein or glycolipid. Two polypeptides recognised by BSLI were
      separated from wool follicle extracts by SDS-gel electrophoresis. These
      polypeptides migrated at approximately 69 kDa and 17 kDa. However, only the 69
      kDa molecule showed the expected loss of binding by BSLI in the presence of alpha
      D-galactose. Further work will be required to determine if this glycoprotein is
      the bulb cell molecule recognised by BSLI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400638
TI  - A functional model of adult human prostate epithelium. The role of androgens and
      stroma in architectural organisation and the maintenance of differentiated
      secretory function.
AB  - A functional model of adult human prostate epithelium is described. This model
      shows that stromal cells, but not an androgenic stimuli, are required for
      architectural organisation of prostate epithelium. Within an organised structure,
      androgenic stimulation is required for the establishment of secretory epithelial
      cell morphology and associated function. In the absence of stromal cells but in
      the presence of androgens architectural organisation and secretory function are
      lost. Epithelial parenchymal units (organoids) from human prostate tissue were
      isolated, cultured within a three-dimensional collagen matrix, and xenografted
      subcutaneously into athymic mouse hosts. The grafted gels were rapidly invaded by
      host fibroblasts. Epithelial organisation initially disappeared but was re
      established concurrently with the stromal cell invasion. In intact male hosts,
      cuboidal and columnar cells that expressed human prostate-specific secretory
      markers were found. In castrated male and in female hosts epithelial structures
      were lined with flattened epithelium with no secretory function. This phenomenon
      could be reversibly replicated by treating intact male hosts with the anti
      androgen Flutamide. Gels containing organoids grafted within 0.45 microns
      Millipore chambers were not invaded by stromal cells and rapidly lost all
      epithelial organisation and secretory function. When organoids cocultured with
      human foreskin fibroblasts were grafted within chambers, structural organisation
      of the epithelium was supported. These results indicate that both heterologous
      human fibroblasts and mouse stromal cells are capable of permissively supporting
      adult human prostate epithelial function.

PMID- 1400639
TI  - Mechanisms of epibolic tissue spreading analyzed in a model morphogenetic system.
      Roles for cell migration and tissue contractility.
AB  - The processes responsible for epithelial spreading during wound healing and
      embryonic morphogenesis were investigated in an organ culture model in which an
      epithelial tissue (chick embryo pigmented retinal epithelium) spread over the
      surface of an aggregate of mesenchyme cells (chick embryo cardiac mesenchyme).
      The heart mesenchyme aggregate is differentiated into a core of stellate cells
      associated with a fibronectin-poor matrix surrounded by a cortical zone, 2-5
      cells in thickness, of flattened cells embedded in a fibronectin-rich
      extracellular matrix. Envelopment of the mesenchyme aggregate is accompanied by a
      movement of the cells and the fibronectin-rich extracellular matrix of the cortex
      over the core tissue in advance of the spreading pigmented retina tissue. Three
      distinct processes were identified as contributing to epithelial spreading in
      this system: (1) active migration of the pigmented retinal epithelium; (2) active
      contraction of the cortical cells of the mesenchyme aggregate to tow the attached
      epithelial tissue over the mesenchyme aggregate; and (3) ingression of surface
      located cells of the mesenchyme aggregate to decrease the exposed surface area by
      decreasing the number of cells at the surface.

PMID- 1400640
TI  - Plasticity in the rat hippocampal formation following ibotenic acid lesion of the
      septal region: a quantitative [14C]deoxyglucose and acetylcholinesterase study.
AB  - The local cerebral glucose utilization was measured in the hippocampal formation
      3, 21, and 90 days after bilateral lesions of the medial septal nucleus and the
      nucleus of the diagonal band of Broca by multiple ibotenic acid injections. The
      CMRglc was determined in hippocampal areas and layers and various limbic and
      visual regions by quantitative [14C]2-deoxyglucose autoradiography using a
      computerized image-processing system. Three days after lesion, CMRglc was
      significantly decreased in 26 of the 38 structures examined. The most pronounced
      reductions were found in CA2 and CA3, the subiculum, and the parasubiculum. The
      CMRglc values of the 21- and 90-day postlesion groups did not differ
      significantly from control data when univariate statistics were used. However, by
      means of a factor analysis and subsequently a discriminant analysis as a
      multivariate test for group differences, significant lesion-induced CMRglc
      changes could be detected between the control group, the 3-day group, and the 90
      day group. The 21-day group did not differ significantly from the controls. The
      data indicate that 90 days after lesion of the medial septum/diagonal band
      complex (MSDB), a considerable recovery of the mean CMRglc was found in the
      hippocampal region, although a normal level was not reached. In a parallel
      series, processing of sections for acetylcholinesterase (AChE) histochemistry
      revealed a severe destruction of AChE-positive fibers in the hippocampus at 3
      days after lesion and a conspicuous recovery in the amount of stainable fibers
      and their staining intensity at 21 days postlesion. In the 90-day group, the AChE
      fibers recovered even further but did not reach the values of unlesioned sham
      operated controls. The present study indicates that sprouting of surviving
      cholinergic afferents might be an important morphological substrate for CMRglc
      recovery in the hippocampus after MSDB lesion.

PMID- 1400642
TI  - A comparison of regional cerebral blood flow and middle cerebral artery blood
      flow velocities: simultaneous measurements in healthy subjects.
AB  - Blood flow velocities were measured in both middle cerebral arteries (MCAs) of 36
      healthy subjects using transcranial Doppler ultrasound. Measurements were first
      made using a hand-held probe. Velocities were then studied bilaterally with fixed
      probes under resting conditions and during simultaneous regional CBF (rCBF)
      measurements. A significant (p < 0.05) positive correlation was found between MCA
      flow velocities and rCBF in the estimated perfusion territory of this artery. The
      correlation coefficient was highest when the measurements were performed
      simultaneously (p < 0.001) or when velocities recorded with a hand-held probe
      were adjusted to take into account the significant velocity increase induced by
      the CBF study situation. The increased velocities during CBF measurements cannot
      be fully explained by the moderate but significant PCO2 increase. Other possible
      mechanisms are increased blood flow due to mental activation or MCA
      vasoconstriction secondary to stimulation of the sympathetic nervous system. The
      effect of mental activation and PCO2 differences should therefore be considered
      when comparing the results of repeated velocity and CBF measurements.

PMID- 1400641
TI  - Cerebral lactate turnover after electroshock: in vivo measurements by 1H/13C
      magnetic resonance spectroscopy.
AB  - We reported earlier that brain activation by 10 s of cortical electroshock caused
      prolonged elevation of brain lactate without significant change in intracellular
      pH, brain high-energy phosphorylated metabolites, or blood gases. The metabolic
      state of the elevated lactate has been investigated in further experiments using
      combined, in vivo 1H-observed 13C-edited nuclear magnetic resonance spectroscopy
      (NMRS), homonuclear J-edited 1H-NMRS, and high-resolution 1H-NMRS of perchloric
      acid extracts to monitor concentrations and 13C-isotopic fractions of brain and
      blood lactate and glucose. We now report that electroshock-elevated lactate pool
      in rabbit brain approaches equilibrium with blood glucose within 1 h. There was
      nearly complete turnover of the raised lactate pool in brain; any pool of
      metabolically inactive lactate could not have been > 5% of the total. In the same
      experiments, blood lactate underwent < 50% turnover in 1 h. The new 1H
      spectroscopic methods used for these experiments are readily adaptable for the
      study of human brain and may be useful in characterizing the metabolic state of
      elevated lactate pools associated with epilepsy, stroke, trauma, tumors, and
      other pathological conditions.

PMID- 1400643
TI  - Hyperglycemia and blood-brain barrier glucose transport.

PMID- 1400644
TI  - A three-dimensional statistical analysis for CBF activation studies in human
      brain.
AB  - Many studies of brain function with positron emission tomography (PET) involve
      the interpretation of a subtracted PET image, usually the difference between two
      images under baseline and stimulation conditions. The purpose of these studies is
      to see which areas of the brain are activated by the stimulation condition. In
      many cognitive studies, the activation is so slight that the experiment must be
      repeated on several subjects and the subtracted images are averaged to improve
      the signal-to-noise ratio. The averaged image is then standardized to have unit
      variance and then searched for local maxima. The main problem facing
      investigators is which of these local maxima are statistically significant. We
      describe a simple method for determining an approximate p value for the global
      maximum based on the theory of Gaussian random fields. The p value is
      proportional to the volume searched divided by the product of the full widths at
      half-maximum of the image reconstruction process or number of resolution
      elements. Rather than working with local maxima, our method focuses on the Euler
      characteristic of the set of voxels with a value larger than a given threshold.
      The Euler characteristic depends only on the topology of the regions of high
      activation, irrespective of their shape. For large threshold values this is
      approximately the same as the number of isolated regions of activation above the
      threshold. We can thus not only determine if any activation has taken place, but
      we can also estimate how many isolated regions of activation are present.

PMID- 1400645
TI  - Individual integration of positron emission tomography and high-resolution
      magnetic resonance imaging.
AB  - We have developed, validated, and employed a technique of retrospective spatial
      alignment and integrated display of positron emission tomographic (PET) and high
      resolution magnetic resonance (MR) brain images. The method was designed to
      improve the anatomical evaluation of functional images obtained from single
      subjects. In the first computational step, alignment of PET and MR data sets is
      achieved by iteratively matching in three orthogonal views the outermost scalp
      contours derived from front-to-back projections of each data set. This procedure
      avoids true three-dimensional modeling, runs without user interaction, and
      tolerates missing parts of the head circumference in the image volume, as usually
      the case with PET. Thereafter, high-resolution MR sections corresponding to the
      PET slices are reconstructed from the spatially transformed MR data. In a phantom
      study of this method, PET/MR alignment of the phantom's surface was accurate with
      average residual misfits of 2.17 to 2.32 mm as determined in three orthogonal
      planes. In-plane alignment of the phantom's insertion holes was accurate with an
      average residual misfit of 2.30 mm. In vivo application in six subjects allowed
      the individual anatomical localization of regional CBF (rCBF) responses obtained
      during unilateral manual exploration. In each subject, the maxima of the rCBF
      activations in the hand area were precisely allocated to gray matter in the
      anterior or posterior wall of the central sulcus. The configuration of the rCBF
      responses closely followed the gyral structures. The technique provided a better
      topographical understanding of rCBF changes in subtraction images of PET
      activation studies. It opens the perspective for studies of structural-functional
      relationships in individual subjects.

PMID- 1400646
TI  - Viability of neocortical function shown in behavioral activation state PET
      studies in Alzheimer disease.
AB  - Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14
      normal elderly control subjects were studied using [18F]fluorodeoxyglucose and
      positron emission tomography (PET) to investigate regional cerebral glucose
      metabolism during both a resting state and a behavioral activation state,
      utilizing a reading memory task (RMT). The RMT produced significant global
      metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD
      subjects. The occipital regions were preferentially activated, but all regions in
      both groups were also significantly activated. The RMT did not allow a better
      discrimination of AD patients from normal controls on the basis of regional
      metabolic deficits. Regions in the AD group that were individually classified as
      hypometabolic during rest also exhibited metabolic activation. The apparent
      viability of hypometabolic regions in AD patients challenges current hypotheses
      regarding the cause of abnormal metabolism in AD.

PMID- 1400647
TI  - Development and remodeling of cerebral blood vessels and their flow in postnatal
      mice observed with in vivo videomicroscopy.
AB  - Changes of blood vessels in the mouse somatosensory (barrel) cortex were assessed
      from birth (P0) to adulthood. Surface vessel anatomy and flow were observed
      directly with videomicroscopy through closed cranial windows and with
      intravascular fluorescent tracers. Histology was used to determine the internal
      capillary density. At birth, arterioles had numerous anastomoses with each other,
      pial capillaries formed a dense surface plexus, and pial venules and veins were
      relatively small and irregular. Morphological changes over the next 2 weeks
      included (a) fewer arteriolar anastomoses, (b) formation and growth of venules,
      (c) more uniform diameters of all types of vascular segments, (d) increase in
      intraparenchymal capillary length density (Lv), and (e) decreases in superficial
      capillary density and diameters. A simple morphological test showed that wall
      shear rates at arteriolar branch points were matched on average in neonates and
      adults. Flow characteristics in single vessels were evaluated. In arterioles of
      like diameters, (a) Vmax, (b) peak wall shear rates, and (c) peak flows were
      similar at all ages; (d) velocity was very high in occasional arteriovenous (AV)
      shunts in newborns; and (e) flow in arteriolar anastomoses was slow and variable.
      Although flow was heterogeneous in all types of vessel, the marked similarities
      in newborn and adult mice of average peak velocities and calculated wall shear
      rates in arterioles of the same size suggest that blood flow regulates in part
      the remodeling of blood vessels during development (Rovainen et al., 1992). The
      rodent barrel cortex undergoes major neuronal and vascular development,
      functional differentiation, and remodeling during the first weeks after birth. It
      provides special opportunities for testing how blood vessels grow and adapt to
      supply the local metabolic requirements of neural modules in the brain.

PMID- 1400648
TI  - Effect of nitric oxide blockade by NG-nitro-L-arginine on cerebral blood flow
      response to changes in carbon dioxide tension.
AB  - The importance of nitric oxide (NO) for CBF variations associated with arterial
      carbon dioxide changes was investigated in halothane-anesthetized rats by using
      an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (NOLAG). CBF was
      measured by intracarotid injection of 133Xe. In normocapnia, intracarotid
      infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of
      arterial blood pressure and a decrease of normocapnic CBF from 85 +/- 10 to 78 +/
      6, 64 +/- 5, and 52 +/- 5 ml 100 g-1 min-1, respectively. This effect lasted for
      at least 2 h. Raising PaCO2 from a control level of 40 to 68 mm Hg increased CBF
      to 230 +/- 27 ml 100 g-1 min-1, corresponding to a percentage CBF response (CO2
      reactivity) of 3.7 +/- 0.6%/mm Hg PaCO2 in saline-treated rats. NOLAG attenuated
      this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined
      with angiotensin to raise blood pressure to the same level as the highest dose of
      NOLAG did not affect the CBF response to hypercapnia. L-Arginine significantly
      prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and
      also abolished its inhibitory effect on hypercapnic CBF. D-Arginine had no such
      effect. Decreasing PaCO2 to 20 mm Hg reduced control CBF to 46 +/- 3 ml 100 g-1
      min-1 with no further reduction after NOLAG. Furthermore, NOLAG did not change
      the percentage CBF response to an extracellular acidosis induced by acetazolamide
      (50 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400649
TI  - Functional changes in thalamic relay neurons after focal cerebral infarct: a
      study of unit recordings from VPL neurons after MCA occlusion in rats.
AB  - We evaluated neuronal and histological changes of thalamic neurons 1, 4, 7, and
      14 days after middle cerebral artery (MCA) occlusion in rats. After the
      somatosensory evoked potentials (SEPs) were measured from the cerebral cortex,
      the thalamic relay neuronal activities were recorded with a glass microelectrode
      following repetitive electrical stimulation of the contralateral forepaw at
      frequencies ranging from 1 to 50 Hz. In approximately 95% of the occluded rats,
      the ipsilateral somatosensory cortex and/or the subcortical somatosensory pathway
      developed infarct, resulting in SEP loss. We evaluated unit data from rats with
      abolished SEPs. The average firing rate of the nucleus ventralis posterolateralis
      (VPL) neurons in response to 25 stimulations at 30 Hz was significantly reduced
      to 0.1 spike/stimulus 1 day after MCA occlusion. In sham-operated rats, the same
      stimulation produced 0.7 spike/stimulus. The firing rate recovered to 0.4
      spike/stimulus at 30-Hz stimulation 4 and 7 days after occlusion. This was
      followed by resuppression (0.1 spike/stimulus) 14 days after occlusion.
      Histological study revealed some abnormal neurons in the ipsilateral thalamus 7
      days after occlusion. We were unable to find normal-shaped neurons in the VPL 14
      days after occlusion. The present study demonstrates that cortical infarct
      produces functional and morphologic changes that gradually and progressively
      affect the ipsilateral thalamus, although incomplete transient recovery of
      somatosensory transmission may occur.

PMID- 1400650
TI  - Stimulation of the fastigial nucleus enhances EEG recovery and reduces tissue
      damage after focal cerebral ischemia.
AB  - Stimulation of the cerebellar fastigial nucleus (FN) increases CBF but not
      metabolism and reduces the tissue damage resulting from focal cerebral ischemia.
      This effect may result from enhancing CBF in the ischemic tissue without
      increasing local metabolic demands. To test this hypothesis, we studied whether
      the reduction in tissue damage is restricted to the neocortex, a region in which
      the CBF increase is independent of metabolism, and whether stimulation of the
      dorsal medullary reticular formation (DMRF), a treatment that increases both
      cerebral metabolism and CBF, also protects the brain from ischemia. In halothane
      anesthetized Sprague-Dawley rats, the middle cerebral artery (MCA) was occluded
      either proximally or distally to the lenticulostriate branches. The FN or DMRF
      were then stimulated for 1 h (50-100 microA; 50 Hz; 1 s on/l s off). Twenty-four
      hours later, the infarct volume was determined. FN stimulation substantially
      reduced the size of the infarct, an effect that was greater with distal (-69 +/-
      8%; n = 6; p < 0.001; mean +/- SD) than with proximal (-38 +/- 8%; n = 8; p <
      0.001) MCA occlusion. The reduction occurred only in neocortex (-43 +/- 9%; p <
      0.001) and not in striatum (-16 +/- 21%; p > 0.05). Stimulation of the FN also
      enhanced recovery of EEG amplitude in the ischemic cortex (+48%; p < 0.003). DMRF
      stimulation (n = 7) did not affect the stroke size or EEG recovery (p > 0.05).
      Thus, stimulation of the FN, but not the DMRF, attenuates the damage resulting
      from focal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400651
TI  - Focal cerebral ischemia in rats: effect of hemodilution with alpha-alpha cross
      linked hemoglobin on CBF.
AB  - Hemodilution has had limited success as a treatment of cerebral ischemia. When
      using a nonoxygen binding fluid, the therapeutic efficacy of hemodilution-induced
      increases in CBF are offset by concomitant decreases in oxygen content. The
      effect of hemodilution, with diaspirin alpha-alpha cross-linked hemoglobin
      (DCLHb), on CBF during middle cerebral artery occlusion was assessed. Rats were
      hemodiluted to one of the following hematocrits (Hct): (a) 44/Hct, (b) 37/Hct,
      (c) 30/Hct, (d) 23/Hct, (e) 16/Hct, or (f) 9/Hct. After 10 min of ischemia, CBF
      was determined with 14C-iodoantipyrine. Coronal brain sections were evaluated for
      areas with a CBF of 0-10 and 11-20 ml 100 g-1 min-1. In addition, oxygen delivery
      was calculated. In the center of the ischemic zone, both areas of low CBF were
      less in the 30/Hct, 23/Hct, and 16/Hct groups compared with the 44/Hct and 37/Hct
      groups; and both areas were less in the 9/Hct group compared with the other five
      groups (p < 0.05). For the hemisphere contralateral to occlusion, there was a
      direct correlation between hematocrit and oxygen delivery. However, for the
      hemisphere ipsilateral to occlusion, oxygen delivery increased as hematocrit
      decreased (44/Hct, 8.6 +/- 0.3 vs. 9/Hct, 13.6 +/- 0.4 [mean +/- SD, ml 100 g-1
      min-1]). The results of this study support a hypothesis that hemodilution with
      DCLHb decreases the extent of focal cerebral ischemia.

PMID- 1400652
TI  - Effects of temperature on evoked electrical activity and anoxic injury in CNS
      white matter.
AB  - Temperature is known to influence the extent of anoxic/ischemic injury in gray
      matter of the brain. We tested the hypothesis that small changes in temperature
      during anoxic exposure could affect the degree of functional injury seen in white
      matter, using the isolated rat optic nerve, a typical CNS white matter tract
      (Foster et al., 1982). Functional recovery after anoxia was monitored by
      quantitative assessment of the compound action potential (CAP) area. Small
      changes in ambient temperature, within a range of 32 to 42 degrees C, mildly
      affected the CAP of the optic nerve under normoxic conditions. Reducing the
      temperature to < 37 degrees C caused a reversible increase in the CAP area and in
      the latencies of all three CAP peaks; increasing the temperature to > 37 degrees
      C had opposite effects. Functional recovery of white matter following 60 min of
      anoxia was strongly influenced by temperature during the period of anoxia. The
      average recovery of the CAP, relative to control, after 60 min of anoxia
      administered at 37 degrees C was 35.4 +/- 7%; when the temperature was lowered by
      2.5 degrees C (i.e., to 34.5 degrees C) for the period of anoxic exposure, the
      extent of functional recovery improved to 64.6 +/- 15% (p < 0.00001). Lowering
      the temperature to 32 degrees C during anoxic exposure for 60 min resulted in
      even greater functional recovery (100.5 +/- 14% of the control CAP area).
      Conversely, if temperature was increased to > 37 degrees C during anoxia, the
      functional outcome worsened, e.g., CAP recovery at 42 degrees C was 8.5 +/- 7% (p
      < 0.00001). Hypothermia (i.e., 32 degrees C) for 30 min immediately following
      anoxia at 37 degrees C did not improve the functional outcome. Many processes
      within the brain are temperature sensitive, including O2 consumption, and it is
      not clear which of these is most relevant to the observed effects of temperature
      on recovery of white matter from anoxic injury. Unlike the situation in gray
      matter, the temperature dependency of anoxic injury cannot be related to reduced
      release of excitotoxins like glutamate, because neurotransmitters play no role in
      the pathophysiology of anoxic damage in white matter (Ransom et al., 1990a). It
      is more likely that temperature affects the rate of ion transport by the Na(+)
      Ca2+ exchanger, the transporter responsible for intracellular Ca2+ loading during
      anoxia in white matter, and/or the rate of some destructive intracellular
      enzymatic mechanism(s) activated by pathological increases in intracellular Ca2+.

PMID- 1400653
TI  - Regional expression of c-fos and heat shock protein-70 mRNA following hypoxia
      ischemia in immature rat brain.
AB  - Cerebral ischemia induces the expression of a number of proteins that may have an
      important influence on cellular injury. The purpose of this study was to compare
      the regional effects of hypoxia-ischemia on the expression of the proto-oncogene,
      c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain.
      Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15,
      and 23 days after birth) using a combination of carotid artery ligation and
      systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression
      of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates
      were permitted to recover for 1 week for assessment of histologic injury. Hypoxia
      ischemia increased the expression of both c-fos and HSP-70 mRNA, but the
      topography of expression varied with the age of the animal as well as the mRNA
      species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple
      regions of the ipsilateral hemisphere in nearly one-half of the animals, while
      HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the
      hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h
      in the entorhinal cortex and in the dendritic field of the upper blade of the
      hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in
      neocortex and the cell layers of the hippocampus. Interestingly, the strong
      expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost
      layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400654
TI  - The concept of environment is deceptively simple.

PMID- 1400655
TI  - Earth dwelling.

PMID- 1400656
TI  - The biosphere and the healing arts.

PMID- 1400657
TI  - Modern physics, synchronicity and intuition.

PMID- 1400658
TI  - Holding sacred space: the nurse as healing environment.

PMID- 1400659
TI  - Congregate dining programs for older adults: a personal view.

PMID- 1400660
TI  - The impact of noise on critically ill people.

PMID- 1400661
TI  - Lightwave frequency and sleep-wake frequency in well, full-term neonates.

PMID- 1400662
TI  - Living and working in space: evolution of nursing in a new environment.

PMID- 1400663
TI  - Estimation of aqueous solubility of organic molecules by the group contribution
      approach. Application to the study of biodegradation.
AB  - A reliable and generally applicable aqueous solubility estimation method for
      organic compounds based on a group contribution approach has been developed. Two
      models have been established based on two different sets of parameters. One has a
      higher accuracy, while the other has a more general applicability. The prediction
      potentials of these two models have been evaluated through cross-validation
      experiments. For model I, the mean cross-validated r2 and SD for 10 such cross
      validation experiments were 0.946 and 0.503 log units, respectively. While for
      model II, they were 0.953 and 0.546 log units, respectively. Applying our models
      to estimate the water solubility values for the compounds in an independent test
      set, we found that model I can be applied to 13 out of 21 compounds with a SD
      equal to 0.58 log unit and model II can be applied to all the 21 compounds with a
      SD equal to 1.25 log units. Our models compare favorably to all the current
      available water estimation methods. A program based on this approach has been
      written in FORTRAN77 and is currently running on a VAX/VMS system. The program
      can be applied to estimate the water solubility of the water solubility of any
      organic chemical with a good or fairly good accuracy except for except for
      electrolytes. Applying our aqueous solubility estimation models to biodegradation
      studies, we found that although the water solubility was not the sole factor
      controlling the rate of biodegradation, ring compounds with greater solubilities
      were more likely to biodegrade at a faster rate. The significance of the
      relationship between water solubility and biodegradation activity has been
      illustrated by predicting the biodegradation activity of 27 new chemicals based
      solely on their estimated solubility values.

PMID- 1400664
TI  - The Concise Connection Table: collected definitions with extensions for
      stereochemistry and saccharides.
AB  - The Concise Connection Table is a representation of molecular structures based on
      an implicit hierarchy of substructural components. This paper introduces a number
      of enhancements and extensions to the original definition, particularly relating
      to representations of stereochemistry and saccharides, and summarizes the overall
      principles of the CCT in one definitive presentation.

PMID- 1400665
TI  - DrawPerfect and CorelDraw.

PMID- 1400666
TI  - Seizure in a polypharmacy household.

PMID- 1400667
TI  - Our healthcareopathy and its 'meltdown'.

PMID- 1400668
TI  - Urinary incontinence in older adults.
AB  - A frequent and largely neglected problem, incontinence in the elderly can often
      be ameliorated or cured. Transient incontinence is usually secondary to
      intercurrent disease and thus should be addressed by treatment of that pathology.
      Established incontinence is most often due to detrusor hyperactivity. Behavioral
      intervention and bladder relaxants are management options.

PMID- 1400669
TI  - Left ventricular hypertrophy and diastolic dysfunction.
AB  - The hypertrophied heart generally preserves systolic function, but it pays a
      price in diastolic dysfunction. Coronary reserve is impaired and susceptibility
      to myocardial ischemia increased. The pathophysiology is managed by addressing
      causes of pressure overload, preventing tachycardia, or, of course, by specific
      strategies to reduce or eliminate ischemia.

PMID- 1400670
TI  - Artificial life.

PMID- 1400671
TI  - Let the people choose.

PMID- 1400672
TI  - Acute chest pain and a wide QRS complex.

PMID- 1400673
TI  - Do vascular wall cytokines promote atherogenesis?
AB  - Protein mediators commonly associated with inflammatory and immune responses may
      also convey signals among vascular endothelial and smooth muscle cells, thereby
      mediating the evolution of hyperplastic arterial disease. A picture is emerging
      in which cytokine expression, lipoprotein modification, and atheroma development
      are interlocking processes.

PMID- 1400674
TI  - Magnetic resonance angiography in peripheral artery disease.

PMID- 1400675
TI  - Shakes and flashes in a relapsed alcoholic.

PMID- 1400676
TI  - Albert Calmette: a vaccine and its vindication.

PMID- 1400677
TI  - A dialogue on diagnosis.

PMID- 1400678
TI  - Federalism, diversity, and freedom of choice.

PMID- 1400679
TI  - Deciding to discontinue antiepileptic medication.

PMID- 1400680
TI  - Intravenous IgG for treatment of autoimmune disease.

PMID- 1400681
TI  - The management of abnormal uterine bleeding.

PMID- 1400682
TI  - The fate of implantable silicone.

PMID- 1400683
TI  - Evaluation and management of dyspepsia.

PMID- 1400685
TI  - Obsessive-compulsive disorder in childhood and adolescence: a clinical study.
AB  - The clinical records of 72 children and adolescents aged 5-18 with a diagnosis of
      OCD were examined. Mean age of onset was 11 years. Repeating, cleaning and
      checking were the most common compulsions. Twenty percent of subjects showed
      obsessions unrelated to compulsions. In 53% of cases stress situations preceded
      the disorder. Seventy-seven percent of subjects suffered some other psychiatric
      disorder, lifetime or current, particularly anxiety and affective disorders. The
      majority (57%) had some first-degree relative with a psychiatric diagnosis.
      Family conflicts, social withdrawal and poor school performance were also common
      features.

PMID- 1400684
TI  - Agreement between parents' reports and adolescents' self-reports of problem
      behavior.
AB  - Parents' reports and adolescents' self-reports of problem behaviors in 883 11-19
      year-olds from the general population were compared. Correlations between both
      informants' CBCL syndrome scores ranged from 0.27 to 0.56. Adolescents reported
      many more problems than their parents did about them. Discrepancies were larger
      for externalizing than for internalizing problems, were larger for girls than for
      boys and increased with age. The findings indicated that adolescents, especially
      as they grow older, are indispensable informants on their own problem behaviors.

PMID- 1400686
TI  - Attainments of severely mentally retarded adolescents by aetiology.
AB  - Piagetian cognitive level, language abilities, adaptive behaviour and graphic
      skills were assessed in three groups of adolescents with severe learning
      difficulties: Down's syndrome (DS), congenital cerebral palsy (CP) and unknown
      origin (NSP). Results were compared with assessments made seven years earlier. A
      wide range of scores was observed in each group. Medians of the DS and NSP groups
      were similar and generally were significantly higher than those of the CP group.
      When the number and severity of other impairments and disabilities (HDCP) was
      taken into account, group averages of attainments and progress were very similar.
      Implications for intervention are discussed.

PMID- 1400687
TI  - Family change, parental discord and early offending.
AB  - The relationship between exposure to family change, exposure to parental discord
      during the period from birth to 10 years and risks of offending by the age of 13
      years was studied in a birth cohort of New Zealand children. This analysis showed
      that while exposure to parental discord during middle and early childhood led to
      increased risks of early offending, exposure to family change in the absence of
      parental discord did not lead to increased risks of offending. The results also
      suggested that children with a history of early conduct problems were
      particularly susceptible to parental discord but that the effects of discord did
      not vary with the child's gender. These results persisted when errors of
      measurement in the reporting of offending were taken into account using latent
      class methods.

PMID- 1400688
TI  - Pre- and perinatal factors and the risk of subsequent referral for hyperactivity.
AB  - Possible pre- and perinatal risk factors for subsequent referral for
      hyperactivity were assessed by comparing birth records of 129 referrals with the
      remaining 24,656 members of a geographically defined birth cohort. Relationships
      between the risk factors were accounted for using logistic regression methods.
      The significant factors were: social class, maternal age, antepartum haemorrhage,
      length of labour (second stage), 1-min Apgar and sex. Associations between
      referral for hyperactivity and the pregnancy, labour and birth outcome factors
      were not explained by the socio-demographic variables. The results suggest that
      such factors have a statistically significant association with referral for
      hyperactivity and may be of modest aetiological importance. However, the
      predictive power of the final set of factors remained low even on the original
      data set.

PMID- 1400689
TI  - The effect of delay on hyperactive and non-hyperactive children's response times:
      a research note.
AB  - Twenty-four hyperactive and 55 non-hyperactive children made a button press after
      the disappearance of a stimulus presented for either 1, 15 or 30 sec. Hyperactive
      children's responses were generally slower than those of non-hyperactive children
      and increased with length of pre-response delay, while non-hyperactive children's
      response time remained the same across all presentation levels. The results are
      interpreted as giving support to accounts that stress the role of pre-response
      delay, rather than time on task per se, as an important determinant of
      hyperactive children's attentional performance.

PMID- 1400690
TI  - Children's drawings of topics differing in emotional significance--effects on
      placement relative to a self-drawing: a research note.
AB  - Children aged 4-6 years were asked to add drawings of someone they liked and
      someone they disliked to a picture of themselves. Liked figures were drawn closer
      than disliked figures to the self-figure only when the procedure was standardized
      and controlled so as to equate the tasks of positioning each of the added
      figures. With unmatched positioning tasks there was no effect of significance of
      figure on placement. The data demonstrate that a child's emotional attitude to a
      figure can affect its placement in a drawing, but that the effect is weak and
      easily masked.

PMID- 1400691
TI  - Understanding drawings and beliefs: a further test of the metarepresentation
      theory of autism: a research note.
AB  - Leslie (1987, Psychological Review, 94, 412-426) proposed that the "theory of
      mind" deficit in autism was the result of a metarepresentation impairment.
      Studies employing False Photograph or Belief tests have shown that in autism the
      deficit is restricted to representing mental representations, and does not extend
      to representing pictorial representations. In this study, we tested this claim
      further using a False Drawing test. Subjects with autism performed at the same
      level as mentally handicapped or normal 4-year-old subjects on the False Drawing
      test, but significantly worse on the False Belief test. This confirmed the
      specificity of the deficit in autism.

PMID- 1400692
TI  - Phonological factors in spelling development.

PMID- 1400694
TI  - Psychometric evaluation of a revised fear survey schedule for children and
      adolescents.
AB  - This study describes the second revision of a fear survey schedule for children
      which was originally developed by Scherer and Nakamura in the 1960's. The revised
      instrument (FSSC-II) was psychometrically evaluated on a sample of 918 children
      and adolescents aged between 7 and 18 years, attending regular primary and
      secondary schools in urban, suburban and rural areas of Victoria. It was
      demonstrated to have high internal consistency. The convergent and divergent
      validity of the revised instrument was examined by correlating it with
      conceptually related as well as distinct scales, respectively. Such analyses
      demonstrated sound validity. A five-factor solution almost identical to that
      reported for the FSSC-R, is described as are age and gender differences. The most
      common fears on the revised instrument are also reported.

PMID- 1400693
TI  - Fears and fearfulness in children and adolescents: a genetic analysis of twin
      data.
AB  - A sample of 175 same sex dizygotic pairs and 144 monozygotic twin pairs aged
      between 8:00 and 18:00 completed the Fear Survey Schedule for Children--Revised.
      The heritabilities were significant for Fear of the Unknown (h2 = 0.46, p less
      than 0.001), Fear of Injury and Small Animals (h2 = 0.46, p less than 0.001),
      Fear of Danger (h2 = 0.34, p less than 0.001) and for Total Fear Score (h2 =
      0.29, p less than 0.001). Multiple regression was used to estimate the
      heritability of extreme fearfulness (h2g). For each of the fear factors the
      values of h2g were of similar magnitude to those of h2 suggesting that there is
      no evidence of greater genetic influences at more extreme levels of fearfulness.

PMID- 1400695
TI  - Sources of distress among New Zealand adolescents.
AB  - This study examined sources of distress experienced by 15-year-old adolescents in
      a large sample from the general population. We identified four types of stressful
      life circumstances relating to problems of self-image and independence, academic
      and physical competence, parental conflict, and moving residence and schools.
      Girls reported higher levels of distress for the first three types of
      circumstance. Reports of distress were associated with poor family social
      support, maternal depression and parental separation. Both DSM-III disorder and
      poor social competence were associated with differential patterns of distress.
      Lastly, poor social competence and high distress were independent and additive
      predictors of mental health disorders.

PMID- 1400696
TI  - Annotation: fragile X syndrome: advances and controversy.

PMID- 1400697
TI  - Out of sight or out of mind? Another look at deception in autism.
AB  - The penny-hiding game is a deception game that occurs naturally in parent-child
      and child-child interaction. It involves minimal linguistic demands, and is lots
      of fun. Oswald and Ollendick (1989) employed it with subjects with autism and
      reported an impaired capacity for deception. They also found that this correlated
      with performance on both a false belief ("theory of mind") test as well as
      various measures of social behaviour. The experiment reported here set out to
      replicate Oswald and Ollendick's important results, and then extend them by using
      a new technique for error analysis. We succeeded in replicating the autism
      specific deception impairment as well as the finding that deception capacity
      correlates highly with performance on a false belief test. In addition, the new
      analytic technique discriminated the group with autism from controls more clearly
      than the traditional index of deception. Specifically, subjects with autism,
      whilst fully capable of enjoying the game as a game of object occlusion (keeping
      things out of sight), failed to perceive the game as a game of information
      occlusion (keeping things out of mind), unlike normal children or subjects with a
      mental handicap of an equivalent or lower mental age. The dissociation in autism
      between occluding objects vs occluding information is discussed in relation to
      other research showing that subjects with autism are impaired in understanding
      the principle that "seeing leads to knowing".

PMID- 1400698
TI  - Comprehension of affect in context in children with pervasive developmental
      disorders.
AB  - Fifteen children with Pervasive Developmental Disorders (PDD) (mean age 12.7
      years) were compared to mental age matched normal children on matching a context
      to its appropriate emotion. PDD children were slightly but significantly impaired
      on this task relative to a non-social task equated for difficulty. Both matching
      tasks were highly correlated with cognitive variables; the social matching task
      alone was correlated with social skill level, and neither task was correlated
      with ratings of social deviance. Results are discussed in terms of the demands of
      social cognitive tasks, the magnitude of social cognitive findings, control group
      selection and individual differences.

PMID- 1400699
TI  - Understanding of simple and complex emotions in non-retarded children with
      autism.
AB  - Non-retarded autistic children are compared to normal controls on measures of
      emotion expression and recognition. In general, autistic subjects recounted
      appropriate examples of simple and complex emotions, and accurately labeled
      relatively ambiguous affect expression in pictures. Autistic children manifested
      some difficulty talking about socially derived emotions, pride and embarrassment.
      They required more time and more prompts, their responses were more tentative and
      "scripted", and they displayed limited understanding of the salience of others in
      embarrassing situations. Results are discussed in relation to theory of mind
      impairment and compensation strategies in autism.

PMID- 1400700
TI  - Children's understanding of the feeling experience and causes of sympathy.
AB  - German children in five age groups, 5-6, 7-8, 9-10, 11-12 and 14-15 years, were
      interviewed about feeling experiences of sympathy and situations that elicit
      sympathy. While the younger children focussed on the emotion of sadness, the
      older children increasingly described sympathy as a multi-dimensional emotional
      experience consisting of sadness, desire to help, and preoccupied thoughts about
      the other in distress. The most marked developmental change occurred in the
      frequency of reference to preoccupied thoughts. The older children regarded
      severe life-threatening distress as situations that elicit sympathy, whereas the
      younger children spontaneously named everyday life distress or favourite animals.

PMID- 1400701
TI  - Early channels of mother-infant communication: preterm and term infants.
AB  - The impact of prematurity on the responsiveness of mothers and their 4-month-old
      infants was examined across three channels of communication: attentional, vocal
      and affective. Log-linear models were used to determine how the behavior of one
      partner was conditional upon the behavior of the other during home observations
      of 24 preterm and 24 term infants and their mothers. Visual attention was
      elicited by vocalization, and the onset of infant gaze was marked by a maternal
      smile. Mothers and infants responded to vocalizations with vocalizations, and
      mothers responded to smiles with smiles. Mothers of preterm infants were
      particularly responsive to their infants' signals within the attentional, vocal
      and affective channels. Preterm infants demonstrated correspondingly heightened
      responsiveness within the vocal and affective channels.

PMID- 1400702
TI  - Soft object and pacifier attachments in young children: the role of security of
      attachment to the mother.
AB  - A longitudinal study was conducted to evaluate the hypothesis that a healthy
      mother-infant relationship is a prerequisite for the development of a child's
      attachment to a blanket or other soft object. Security of attachment to mother
      was measured at 12 months with the Strange Situation Test and at 30 months with
      the Attachment Q-Sort. Most of the children with soft object attachments were
      rated as securely attached to their mothers at both ages. Children with pacifier
      attachments, on the other hand, were less often rated as securely attached and
      were more likely to show changes in security classification between 12 and 30
      months. The results are discussed in terms of necessary, but not sufficient,
      conditions for the development of attachments to inanimate objects.

PMID- 1400703
TI  - Methylphenidate and cognitive perseveration in hyperactive children.
AB  - Effects of methylphenidate on cognitive flexibility were investigated in 26
      children with Attention Deficit Hyperactivity Disorder (ADHD), by assessing
      perseverative errors on the Wisconsin Card Sorting Test (WCST) and the emergence
      of clinical symptoms indicative of cognitive perseveration. A double-blind,
      placebo-control, randomized crossover design was used in which each child was
      assessed twice in each drug condition (placebo, 0.3 and 1.0 mg/kg). Results
      indicated that methylphenidate increased perseverative errors on the first
      assessment but decreased them on the second; clinical symptoms of perseveration
      occurred at both assessments. Findings suggest that MPH may reduce cognitive
      flexibility temporarily in some ADHD children.

PMID- 1400705
TI  - Rising IQ scores in British children: recent evidence.
AB  - Between 1987 and 1990 IQ scores for 333 5-year-old white school children were
      obtained using the Wechsler Pre-School and Primary Scale of Intelligence (WPPSI)
      and the results were compared with 112 children assessed in 1967. The mean full
      scale IQ score of 113.3 was 8 points higher than the mean of 105.1 in the 1967
      study. These findings indicate that the rate of increase of IQ scores was
      comparable and probably higher than that reported in the U.S.A. for the period
      1932-78. It is important that this large increase is taken into account for
      correct interpretation of IQ test results.

PMID- 1400704
TI  - Gender ratios among reading-disabled children and their siblings as a function of
      parental impairment.
AB  - Gender ratios are reported for 374 reading-disabled probands and their 530
      siblings included in five independent studies of reading disability. Ratios were
      tabulated for each study as a function of parental impairment (neither parent
      affected, mother only affected, father only affected, and both parents affected).
      Results reveal a small excess of male probands in referred and clinic samples of
      reading-disabled children, but not in research-identified samples. Gender ratios
      among siblings of reading-disabled probands are approximately 1:1. In addition,
      combined results indicate that gender ratios of neither probands nor their
      siblings vary substantially as a function of parental impairment.

PMID- 1400706
TI  - Toddlers' sleep and temperament: reporting bias or a valid link? A research note.
AB  - Objective sleep measures derived from a computerized movement detector attached
      to the child's leg, were obtained for a group of 31 toddlers (mean age: 18.5
      months). The monitored sleep parameters were compared with maternal assessment of
      the child's sleep and her perception of his temperament. The validity of maternal
      diaries as a measure of the child's sleep was not supported. Nevertheless, a link
      between both subjective and objective sleep measures with temperament dimensions
      was indicated. The modest association between sleep and temperament may suggest
      either a continuity between some aspects of day- and night-time functioning or,
      alternatively, the influence of the child's sleep behavior in shaping the
      mother's perceptions of her toddler's temperament.

PMID- 1400707
TI  - Parent-teacher agreement on kindergarteners' behavior problems: a research note.
AB  - The present study investigated parameters of agreement as well of disagreement
      among mothers' and teachers' ratings of the behavior of kindergarten boys and
      girls. Findings indicated a generally low to moderate level of agreement between
      these two types of informants. They also suggested that demographic and
      background characteristics can effect size and direction of level of agreement.
      Although proportions of children rated as having the listed behavior problems
      varied in magnitude according to mothers and teachers, the rank order of the
      proportion of children with those behavior problems was rather similar for both
      informants. Such similar rankings of prevalence rates may reflect parents' and
      teachers' agreement on the consistency of children's behavior across the home and
      school settings.

PMID- 1400708
TI  - Drug level monitoring: antidepressants.
AB  - The determination of antidepressant drugs which act by blocking neuronal uptake
      of biogenic amines, because of their widespread use and high toxicity, remains
      one of the most commonly requested drug assays in clinical laboratories. Easy to
      use immunoassay reagents for the estimation of these drugs are commercially
      available. However, immunoassays have not been universally accepted because of
      high probability of these reagents producing false negative and false positive
      results. At present, column liquid chromatography with absorbance detection and
      coupled with solid-phase extraction is the most viable technique for a general
      procedure for the identification and determination of these drugs. The technique
      of liquid chromatography is economical, environmental friendly since water
      miscible and biodegradable solvents can be used for extraction of drugs and their
      chromatographic separation, and amenable to full automation. New techniques of
      separation, such as supercritical fluid chromatography and capillary zone
      electrophoresis, have not yet been applied for the determination of therapeutic
      concentrations of antidepressants.

PMID- 1400709
TI  - Simultaneous determination of stable isotopically labelled L-histidine and
      urocanic acid in human plasma by stable isotope dilution mass spectrometry.
AB  - A capillary gas chromatographic-mass spectrometric method for the simultaneous
      determination of stable isotopically labelled L-histidine (L-[3,3-2H2,1',3'
      15N2]histidine, L-His-[M + 4]) and urocanic acid ([3-2H,1',3'-15N2]urocanic acid,
      UA-[M + 3]) in human plasma was developed using DL-[2,3,3,5'-2H4,2'-13C,1',3'
      15N2]histidine (DL-His-[M + 7]) and [2,3,5'-2H3,2'-13C,1',3'-15N2]urocanic acid
      (UA-[M + 6]) as internal standards. L-Histidine and urocanic acid were
      derivatized to alpha N-(trifluoroacetyl)-imN-(ethoxycarbonyl)-L-histidine n-butyl
      ester and imN-(ethoxycarbonyl)urocanic acid n-butyl ester. Quantification was
      carried out by selected ion monitoring of the molecular ions of the respective
      derivatives of L-His-[M + 4], DL-His-[M + 7], UA-[M + 3] and UA-[M + 6]. The
      sensitivity, specificity, precision and accuracy of the method were demonstrated
      to be satisfactory for measuring plasma concentrations of L-His-[M + 4] and UA-[M
      + 3] following administration of trace amounts of L-His-[M + 4] to humans.

PMID- 1400710
TI  - Excretion of formaldehyde, malondialdehyde, acetaldehyde and acetone in the urine
      of rats in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin, paraquat, endrin and
      carbon tetrachloride.
AB  - Formaldehyde (FA), acetaldehyde (ACT), malondialdehyde (MDA) and acetone (ACON)
      were simultaneously identified in urine, and their excretion quantitated in
      response to chemically induced oxidative stress. Urine samples of female Sprague
      Dawley rats were collected over dry ice and derivatized with 2,4
      dinitrophenylhydrazine. The hydrazones of the four lipid metabolic products were
      quantitated by high-performance liquid chromatography on a Waters 10-microns mu
      Bondapak C18 column. The identities of FA, ACT, MDA and ACON in urine were
      confirmed by gas chromatography-mass spectrometry. An oxidative stress was
      induced by orally administering 100 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p
      dioxin, 75 mg/kg paraquat, 6 mg/kg endrin or 2.5 ml/kg carbon tetrachloride to
      rats. Urinary excretion of FA, ACT, MDA and ACON increased relative to control
      animals 24 h after treatment with all xenobiotics. The system has wide-spread
      applicability to the investigation of altered lipid metabolism in disease states
      and exposure to environmental pollutants.

PMID- 1400711
TI  - Identification of 4-hydroxyandrost-4-ene-3,17-dione metabolites in prostatic
      cancer patients by liquid chromatography-mass spectrometry.
AB  - Liquid chromatography with thermospray mass spectrometry has proved to be an
      invaluable technique for the study of metabolic degradation of xenobiotics in
      complex biological fluids. This paper describes the detection of 4-hydroxyandrost
      4-ene-3,17-dione and its metabolites in urinary extracts from prostatic cancer
      patients. Several metabolites were detected including 4 beta,5 alpha
      dihydroxyandrostan-3,17-dione, 3,17-dihydroxyandrostan-4-ones and 3 alpha-hydroxy
      5 beta-androstan-4,17-dione.

PMID- 1400713
TI  - Electrochemical determination of femtomole amounts of free reduced and oxidized
      glutathione. Application to human hair follicles.
AB  - A simple and sensitive high-performance liquid chromatographic technique has been
      developed for the quantification of free reduced and free oxidized glutathione in
      biological samples. After acidic extraction and isocratic separation of the
      compounds of interest on a reversed-phase column, both forms of glutathione are
      quantified with a coulometric detector working in the oxidative mode. The limit
      of detection is 125 fmol for reduced glutathione and 400 fmol for the oxidized
      form (signal-to-noise ratio of 3). This sensitivity allows the measurement of the
      small amount of glutathione present in a single hair follicle. The technique is
      well adapted to microsamples, i.e. for non-invasive sampling technique (hair,
      skin, tears, etc.) and can be adapted to various cells or tissues.

PMID- 1400712
TI  - Preparation of an optimum mobile phase for the simultaneous determination of
      neurochemicals in mouse brain tissues by high-performance liquid chromatography
      with electrochemical detection.
AB  - A systematic method is described for the optimization of a mobile phase for the
      simultaneous determination of 24 neurochemicals consisting of catecholamine,
      serotonin, their precursors and metabolites and related materials. This mobile
      phase contained sodium acetate (0.04 M), citric acid (0.01 M), sodium chloride
      (0.0126 M), sodium octyl sulfate (91 mg/l), tetrasodium EDTA (50 mg/l) and 10%
      (v/v) methanol. When this optimum mobile phase was applied to the analysis of
      brain tissues of the Swiss male mouse, twelve neurochemicals were quantified in
      the free state: tyrosine, L-beta-3,4-dihydroxyphenylanine, dopamine, 3,4
      dihydroxyphenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, norepinephrine,
      3-methoxy-4-hydroxyphenylglycol, DL-3,4-dihydroxymandelic acid, DL-4-hydroxy-3
      methoxymandelic acid, serotonin, L-tryptophan, 5-hydroxyindole-3-acetic acid and
      DL-synephrine and normetanephrine, appearing as a fused peak. This fused peak was
      present on the chromatogram tracings of all the mouse brain tissues. The
      separable neurochemicals not found by this procedure in the Swiss male mouse
      tissues were DL-3,4-dihydroxyphenylglycol,5-hydroxytryptophan, epinephrine, DL
      octopamine, metanephrine, deoxyepinephrine, homovanillyl alcohol, N
      acetylserotonin, tyramine and 3-methyltyramine.

PMID- 1400714
TI  - High-performance liquid chromatographic determination of selenocysteine with the
      fluorescent reagent, N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid.
AB  - The method described is based on derivatization of selenocysteine with N
      (iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid and responds linearly to
      selenocysteine spiked into plasma. Recovery is insensitive to inter-individual
      variation or use of serum versus plasma, but is decreased by hemolysis. The
      derivative is stable for at least three days. The total imprecision of
      determinations in plasma was 0.8-2.1% (coefficient of variation) over the range
      of 6-30 microM selenocysteine, with a detection limit of 0.4 microM (3 x S.D.).
      There was no significant interference from plasma thiols. This appears to be the
      first report of the selective reaction of free selenocysteine with a fluorescent
      reagent. This simple method works well in plasma and serum and may be adaptable
      to other types of samples.

PMID- 1400715
TI  - Resolution of serum aluminum-binding proteins by size-exclusion chromatography:
      identification of a new carrier of aluminum in human serum.
AB  - We have examined the use of TSK-GEL HW 55S for determining the distribution of
      aluminum in human serum by size-exclusion chromatography (SEC). In comparison to
      other SEC matrices, this material has less affinity for ionized aluminum and
      separates serum proteins and their aluminum complexes with greater resolution.
      This enabled the identification of a previously unknown protein carrier,
      provisionally called albindin, that binds aluminum with great stability. Albindin
      appears to be distinct from the previously described aluminum carriers albumin
      and transferrin and may be important in the pathogenesis of disease secondary to
      hyperaluminemia.

PMID- 1400716
TI  - Separation of rat pancreatic secretory proteins by cation-exchange fast protein
      liquid chromatography.
AB  - Rat pancreatic secretory proteins were separated by an automated liquid
      chromatography system utilizing a Mono S cation-exchange column. Optimal
      resolution was obtained with a multistep salt and pH gradient (0.01-2 M LiCl, pH
      5.3-63). A total of fourteen well-separated peaks, as well as several minor
      peaks, were detected by UV absorption. The main pancreatic enzymes were resolved
      (two amylases, two chymotrypsinogens, two trypsinogens, proelastase, lipase,
      prophospholipase A2, procarboxypeptidase A, procarboxypeptidase B, and
      ribonuclease). In addition, proteins without enzymic activity, such as
      lithostathine and pancreatitis-associated protein, were identified. Activation of
      proenzymes did not occur during the separation. At a flow-rate of 0.5 ml/min, ca.
      250 micrograms to 5 mg of protein could be applied with equal resolution. The
      reproducibility of retention volumes and peak areas was high (less than 1% or 5%
      variation, respectively). When radiolabeled proteins were separated, a comparable
      pattern of peaks was obtained. The technique described is, therefore, not only
      useful for analytical and preparative separation of pancreatic proteins but can
      additionally serve for quantitative determination of the pancreatic isoenzyme
      pattern.

PMID- 1400717
TI  - Determination of cobalt in urine by gas chromatography-mass spectrometry
      employing nickel as an internal standard.
AB  - A gas chromatographic-mass spectrometric method for the determination of cobalt
      in biological materials employing stable enriched 62Ni as an internal standard
      and using lithium bis(trifluoroethyl)dithiocarbamate as a chelating agent is
      described. The method involves the addition of a known amount (1 microgram) of
      62Ni to the sample, the formation of the chelate and the determination by
      selected-ion monitoring of the m/z 571/574 ratio, which corresponds to 59Co/62Ni.
      No appreciable memory effect was observed, and an acceptable dynamic range of 100
      was found. There was good agreement between the cobalt concentration values
      determined by gas chromatography-mass spectrometry and electrothermal atomic
      absorption spectrometry. The present method has high sensitivity and can be used
      for the quantitation of cobalt at concentrations as low as 1 microgram/l. The use
      of enriched 62Ni circumvents the problem caused by endogenous nickel and
      simultaneously provides data on the nickel concentration in the biological sample
      without any additional experimental effort.

PMID- 1400718
TI  - Determination of ceftazidime in dolphin serum by liquid chromatography with
      ultraviolet-visible detection and confirmation by thermospray liquid
      chromatography-mass spectrometry.
AB  - A simple and sensitive liquid chromatographic method has been developed for the
      determination of therapeutic levels of ceftazidime in dolphin serum. The method
      involved an ultrafiltration of diluted serum with an equal amount of acetonitrile
      ethanol-water (40:40:20, v/v/v) through a 10,000 daltons molecular mass cut-off
      filter. Separation of ceftazidime from the other serum components was performed
      by ion-paired (dodecanesulfonate) liquid chromatography using a reversed-phase
      column eluted with acetonitrile-water solution. The ultraviolet absorbance of the
      column effluent was monitored in the 200-340 nm range of a photodiode-array
      detector or at 258.8 nm on a variable-wavelength ultraviolet-visible detector.
      Recoveries of ceftazidime from dolphin serum spiked with 20 and 2 micrograms/ml
      were 92.9 and 91.1% with coefficients of variation of 5.5 and 5.7%, respectively.
      A correlation coefficient of 0.9994 occurred with ceftazidime in aqueous
      solutions (n = 6, in duplicates). The limit of detection for this antibiotic was
      estimated to be approximately 50 ppb (ng/ml). The unbound ceftazidime
      concentrations in dosed dolphin serum were determined to calculate the protein
      bindings of this antibiotic which yielded 32 +/- 2%. The ceftazidime peak
      identity in dosed dolphin serum was confirmed by thermospray liquid
      chromatography-mass spectrometry. The thermospray mass spectrum of ceftazidime
      exhibited only the fragment ions, involving the opening of the beta-lactam ring,
      at m/z 237, 255 and 315 when positive-ion detection mode was employed and the
      fragment ions at m/z 235, 253 and 313 when negative-ion detection mode was used.

PMID- 1400719
TI  - Determination of penicillin G in bovine plasma by high-performance liquid
      chromatography after pre-column derivatization.
AB  - A simple, selective, and sensitive liquid chromatographic method with ultraviolet
      detection was developed for the analysis of penicillin G in bovine plasma. The
      assay utilizes a simple extraction of penicillin G from plasma (with a known
      amount of penicillin V added as internal standard) with water, dilute sulphuric
      acid and sodium tungstate solutions, followed by concentration on a conditioned
      C18 solid-phase extraction column. After elution with 500 microliters of elution
      solution, the penicillins are derivatized with 500 microliters of 1,2,4-triazole
      mercuric chloride solution at 65 degrees C for 30 min. The penicillin-mercury
      mercaptide complexes are separated by reversed-phase liquid chromatography on a
      C18 column. The method, which has a detection limit of 5 ng/ml (ppb) in bovine
      plasma, was used to quantitatively measure the concentrations of penicillin G in
      plasma of steers at a series of intervals after the intramuscular administration
      of a commercial formulation of procaine penicillin G.

PMID- 1400720
TI  - High-performance liquid chromatographic determination of sotalol in plasma. I.
      Application to the disposition of sotalol enantiomers in humans.
AB  - Two high-performance liquid chromatographic analytical methods have been
      developed for the measurement of dl-sotalol or d-sotalol and l-sotalol in plasma,
      using dl-atenolol as internal standard. Quantitation of dl-sotalol was carried
      out, following solid-phase extraction, on a 5-microns C18 reversed-phase column,
      with a mobile phase containing acetonitrile, ion-pairing reagent and distilled
      water, using ultraviolet detection at 235 nm. Quantitation of d-sotalol and l
      sotalol was based on derivatisation with the chiral agent S-(-)-alpha
      methylbenzyl isocyanate, followed by chromatographic separation on a 3-microns
      C18 reversed-phase column, with a mobile phase containing methanol, glacial
      acetic acid and distilled water, with fluorimetric detection at 220 nm excitation
      and 300 nm emission. A preliminary application of the latter method suggests that
      the disposition of sotalol in humans is not enantioselective.

PMID- 1400721
TI  - Intra-injector methylation of free fatty acids from aerobically and anaerobically
      cultured Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus.
AB  - Free fatty acids from the type strains of anaerobically and aerobically broth
      cultured Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus cells
      were Soxhlet-extracted with hexane. The fatty acids were identified and
      quantified by gas chromatography and gas chromatography-mass spectrometry after
      intra-injector derivation with trimethylanilinium hydroxide. This derivatization
      method, which we propose as suitable for routine use in clinical microbiology, is
      fast, accurate and sensitive, with low toxicity. Whereas the fatty acid content
      of A. actinomycetemcomitans was affected by the cultivation atmosphere, i.e.
      C16:1, decreased under aerobic growth and C16:0 increased, that of the closely
      related H. aphrophilus was more stable.

PMID- 1400722
TI  - Difference in the concentration of tryptophan metabolites between maternal and
      umbilical foetal blood.
AB  - Maternal and umbilical foetal blood at delivery were analysed for tryptophan
      metabolites by using fully automated high-performance liquid chromatography. The
      metabolites detected in 100 microliters of maternal plasma were kynurenine,
      serotonin, 5-hydroxyindoleacetic acid, indolelactic acid, indoleacetic acid and
      indolepropionic acid. These metabolites were present in various amounts in the
      protein-bound form. Except for indolepropionic acid, the concentrations of
      tryptophan metabolites were significantly higher in umbilical foetal plasma than
      in maternal plasma. In addition, 3-hydroxyanthranilic acid was present in
      umbilical foetal blood, but not in maternal blood. Furthermore, kynurenic acid
      was also detected in amniotic fluids.

PMID- 1400723
TI  - Resolution of three forms of superoxide dismutase by immobilised metal affinity
      chromatography.
AB  - A new method for separation of three forms of superoxide dismutase (SOD) using
      immobilised metal affinity chromatography (IMAC) is reported. Fe-, Mn- and Cu/Zn
      SODs were eluted sequentially from Cu(2+)-IMAC column with an increasing gradient
      of a counter ion (NH+4) run in combination with an increasing pH gradient (6.8
      7.8). The combined gradient elution method resulted in separation of SODs with
      high resolution, the three proteins being eluted in electrophoretically
      homogeneous forms. Similar preparation could not be achieved by either increasing
      gradient of a counter ion or decreasing pH gradients used separately. The
      described methodology has been successfully applied for separation of three SODs
      from a protozoan parasite, indicating that this combined gradient elution system
      for IMAC offers new possibilities for the high-resolution separation of proteins
      exhibiting only minor differences in their amino acid composition and structure.

PMID- 1400724
TI  - Separation of globins using free zone capillary electrophoresis.
AB  - This paper describes the use of high-performance capillary electrophoresis for
      the separation of globin chains. Adult and newborn haemolysates from normal
      individuals and children suspected of having thalassaemia were analysed using
      free zone electrophoresis. Separation of globins was accomplished using a 25 mM
      phosphate buffer at pH 11.8. Distinct peaks of alpha-, beta- and gamma-chains
      were resolved within 8 min. The coefficient of variation for within-day and
      between-day runs was 4.1% and 5.7%, respectively. This method is simple and
      rapid, and it can be used to screen for thalassaemia and for the clinical study
      of various haemoglobinopathies.

PMID- 1400725
TI  - High-performance liquid chromatographic determination of navelbine in MO4 mouse
      fibrosarcoma cells and biological fluids.
AB  - A high-performance liquid chromatographic method is described for separating and
      determining navelbine and possible metabolites in plasma, cell culture medium and
      MO4 cells. Navelbine is extracted from these fluids by ion-pair extraction with
      sodium octylsulphate as the counter-ion at pH 3. The system uses a cyano column
      as the stationary phase and a mobile phase of acetonitrile-0.12 M phosphate
      buffer (pH 3) (60:40, v/v). Application of the method to a study of the
      pharmacokinetic behaviour of navelbine in MO4 mouse fibrosarcoma cells is
      reported.

PMID- 1400726
TI  - Quantitation of a new cholecystokinin and gastrin receptor antagonist (L-365,260)
      in dog and rat plasma by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic (HPLC) procedure has been developed for
      the quantification of L-365,260 (I), a cholecystokinin and gastrin receptor
      antagonist, in dog and rat plasma. The method involves liquid-liquid extraction
      and HPLC with ultraviolet detection. Standard curves were linear over the range
      7.5-2000 ng/ml for rat and dog plasma. The method is reproducible and reliable
      with a detection limit of 7.5 ng/ml in biological fluids. The mean coefficients
      of variation for concentrations within the range of the standard curve range were
      3.84 and 2.56%, respectively, for intra-day analysis and 4.48 and 4.26%,
      respectively, for inter-day analysis. Application of the development was
      successfully demonstrated by quantifying the concentration of I in both dog and
      rat plasma samples following an intravenous or oral dose of 5 mg/kg I.

PMID- 1400727
TI  - Gas chromatographic-mass spectrometric determination of 11-dehydrothromboxane B2
      in human urine.
AB  - The extension of a method for the determination of thromboxane B2 (TxB2), 2,3
      dinor-TxB2, 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and 2,3-dinor-6
      keto-PGF1 alpha to quantify 11-dehydro-TxB2 in the same urinary sample is
      described. After phenylboronic acid and C18 column chromatography, 11-dehydro
      TxB2, which is present in urine as the lactone and its corresponding hydroxy
      acid, was quantitatively converted into its lactone form for a thin-layer
      purification step and pentafluorobenzyl esterification. Quantification of
      eicosanoids was achieved by analysing their trimethylsilyl ethers with gas
      chromatography and negative-ion chemical ionization mass spectrometry. The
      overall recovery from urine for tritiated 11-dehydro-TxB2 was 80%. The detection
      limit was 10 pg/ml. The method was applied to the determination of these
      eicosanoids in volunteers and in patients suffering from acute myocardial
      infarction.

PMID- 1400728
TI  - High-performance liquid chromatographic method for the quantitation of
      bupivacaine, 2,6-pipecoloxylidide and 4'-hydroxybupivacaine in plasma and urine.
AB  - A high-performance liquid chromatographic method with ultraviolet detection at
      210 nm for quantitation of bupivacaine and two of its metabolites from plasma and
      urine is described. The compounds are extracted into n-hexane-isopropanol (5:1),
      evaporated and the reconstituted residue injected onto a reversed phase C18
      column. Standard curves for all compounds were linear (r2 greater than 0.999) in
      the range 20-2000 ng/ml, with a limit of detection of 10 ng/ml. The inter-day
      coefficients of variation ranged between 2.7 and 12.2%. The method was applied to
      analyse bupivacaine and metabolite concentrations in patients on long-term
      epidural bupivacaine-fentanyl infusions.

PMID- 1400729
TI  - Analysis of terbutaline in human plasma by high-performance liquid chromatography
      with electrochemical detection using a micro-electrochemical flow cell.
AB  - A high-performance liquid chromatographic method is described for the
      determination of terbutaline in human plasma in the range 1-35 ng/ml. Detection
      was achieved using a carbon fibre micro-electrochemical detector and a column
      switching system. The microelectrode cell has advantages over conventional glassy
      carbon electrode-based detection systems in that it is easy to prepare, flexible
      in its operation and suffers less trouble from problems such as air bubbles and
      leaks. Furthermore, it has a better detection limit for terbutaline (0.8 ng/ml)
      to that obtained using a conventional glassy carbon electrode flow detector (2
      ng/ml). Sample clean-up was by on-line solid-phase extraction with column
      switching, providing a method which was sensitive and reproducible, where the
      mean overall coefficient of variation was 5.60% and drug recovery in excess of
      86% at the concentration levels studied.

PMID- 1400730
TI  - Determination of lansoprazole and its metabolites in plasma by high-performance
      liquid chromatography using a loop column.
AB  - A high-performance liquid chromatographic method for the simultaneous
      determination of lansoprazole, a new proton pump inhibitor, and its metabolites
      in human plasma is described. Lansoprazole, its metabolites and an internal
      standard were extracted with tert.-butyl methyl ether. Samples were injected
      using an automatic injector via a loop column, and separation was obtained using
      a reversed-phase column under isocratic conditions. The absorbance was monitored
      at 285 and 303 nm. The quantification limit was 2 ng/ml for lansoprazole and 3 or
      5 ng/ml for the metabolites. No endogenous compounds were found to interfere. The
      mean overall recovery was between 75 and 95% for lansoprazole and its
      metabolites. This method is suitable for pharmacokinetic studies.

PMID- 1400731
TI  - Determination of brodimoprim and its hydroxy metabolite in human plasma, blood
      and urine by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method was developed to measure the
      concentration of brodimoprim and its metabolite, hydroxybrodimoprim, in small
      volumes of blood, plasma and urine. The procedure involved a simple extraction
      step with chloroform, followed by chromatographic separation on a short reversed
      phase column deactivated for the analysis of basic compounds. The column effluent
      was monitored by fluorescence (excitation wavelength 290 nm, emission wavelength
      340 nm). The recoveries of both compounds were similar in all three biological
      fluids, and averaged 84 and 72%, respectively. The detection limit for both
      compounds reached 5 ng/ml. No endogenous compound interfered in the assay. The
      linearity of the method and its within- and between-day precision were
      analytically satisfactory.

PMID- 1400732
TI  - Separation of theophylline and its analogues by micellar electrokinetic
      chromatography: application to the determination of theophylline in human plasma.
AB  - Micellar electrokinetic chromatographic separation of theophylline and its
      analogues was investigated using sodium dodecyl sulphate (SDS) as a micellar
      phase. The effects of pH, micelle concentration, applied voltage and temperature
      on the separation and preliminary quantitative analysis were studied for the
      determination of theophylline in human plasma. The data indicate that this
      technique could be used as the reference or routine method of theophylline
      measurement in therapeutic drug monitoring.

PMID- 1400733
TI  - Nucleotide preparation from cells and determination of nucleotides by ion-pair
      high-performance liquid chromatography.
AB  - Procedures for the analysis of cellular purine and pyrimidine nucleotides are
      described. The commonly used perchloric acid and especially the trichloroacetic
      acid methods for nucleotide extraction interfere with ion-pair high-performance
      liquid chromatography, but we have developed such a system for the separation and
      determination of major cellular nucleotides in biological matrices, including tri
      , di-, monophosphates, cAMP, cGMP, NAD, NADP, UDP-glucose and UDP-galactose.
      Compared with perchloric acid extraction, no degradation of the nucleotide
      standards used was observed with respect to triphosphates and other relatively
      unstable nucleotides. Cellular nucleotides were extracted by lysing cells in a
      hypotonic buffer containing an ion-pair reagent (tetrabutylammonium hydrogen
      sulphate) to decrease enzymic degradation of nucleotides in combination with
      ultrafiltration of the cell lysate to remove compounds of higher molecular mass,
      for example enzymes. This method is a simple and reproducible procedure for
      investigating nucleotide pools in cells.

PMID- 1400734
TI  - Improved and simplified tissue extraction method for quantitating long-chain acyl
      coenzyme A thioesters with picomolar detection using high-performance liquid
      chromatography.
AB  - A method has been developed that permits rapid and easy tissue extraction of long
      chain acyl-coenzyme A (acyl-CoA) thioesters with sensitive quantitation by
      reversed-phase high-performance liquid chromatography (RP-HPLC). Tissue
      homogenants are extracted using a reserve Bligh-Dyer technique, and long-chain
      acyl-CoA esters are harvested in the methanolic aqueous phase. Complex lipids and
      phospholipids are removed in the chloroform-rich organic Bligh-Dyer second phase,
      and long-chain acyl-CoA compounds are further purified from the methanolic
      aqueous Bligh-Dyer first phase on C18 extraction columns after removal of the
      methanol. The eluted and purified acyl-CoA esters are then quantitated by RP-HPLC
      using heptadecanoyl-CoA as an internal standard resulting in a detector
      sensitivity of about 12 pmol. Ten long-chain acyl-CoA esters from C12:0 to C20:4
      were identified and separated from canine renal cortex and murine liver samples.
      The predominant acyl-CoA peaks from both kidney and liver were 14:0, 16:1, 16:0,
      18:1, 18:2 and 20:4. Murine liver also produced 18:0 and all peaks disappeared
      after alkaline hydrolysis of the samples. This extraction and quantitation
      technique can successfully be used for tissue samples as small as 20 mg, and many
      samples can be processed in a short period of time. The simplicity of the
      extraction procedure and the sensitivity of the assay make this an attractive
      alternative approach to quantitating long-chain acyl-CoA thioesters from complex
      biological samples such as tissues.

PMID- 1400735
TI  - Determination of retinyl palmitate and total vitamin A content in liver and liver
      based ready-to-eat foods.
AB  - The determination of retinyl palmitate and total vitamin A in liver and liver
      based ready-to-eat foods is described. The method is very simple as sample
      preparation is minimal, and the isocratic elution of the C18 column with pure
      methanol does not necessitate a sophisticated instrumental set-up. The method is
      accurate with high recoveries (100.6 +/- 9.3%, mean +/- S.D., n = 23), and
      precise with within-day and between-day coefficients of variation of less than
      5.5% (n = 13) and less than 16% (n = 6), respectively.

PMID- 1400736
TI  - Simultaneous determination of nitroglycerin and its dinitrate metabolites by
      capillary gas chromatography with electron-capture detection.
AB  - A major problem in the analysis of nitroglycerin (propanetriol trinitrate, GTN)
      and its metabolites [propanetriol 1,2-dinitrate (1,2-GDN) and propanetriol 1,3
      dinitrate (1,3-GDN)] has been the adsorption of the nitro compounds to glass
      apparatus during sample preparation or injection. In this paper we present a
      method determining GTN, 1,2-GDN and 1,3-GDN in plasma at low nanomolar level
      using capillary gas chromatography with electron-capture detection. The detection
      limits are about 0.2 nM in plasma. Adsorption of the nitro compounds to glassware
      is prevented by using triethylamine, giving a simple sample preparation and
      accurate results. Thus, the laborious and time-consuming silanization of the
      glassware is avoided.

PMID- 1400737
TI  - Gas chromatographic determination of meprobamate in serum or plasma after solid
      phase extraction.
AB  - This gas chromatographic technique of determining meprobamate is based on a solid
      phase extraction permitting a time reduction of the analysis and improving
      sensitivity. Quantification is realized on 500 microliters of plasma. The method
      uses etidocaine as internal standard and does not require derivatization. Thus it
      is simple, rapid, sensitive and applicable in forensic and clinical toxicological
      laboratories.

PMID- 1400738
TI  - Automated high-performance liquid chromatographic method for the simultaneous
      determination of cefotiam and delta 3-cefotiam in human plasma using column
      switching.
AB  - An automated high-performance liquid chromatographic method using column
      switching was established for the simultaneous determination of cefotiam (I) and
      delta 3-cefotiam (II) in human plasma after oral administration of cefotiam
      hexetil dihydrochloride. The method allowed the determination of analytes in
      plasma by the direct injection of diluted specimen with phosphate buffer. The
      analytes were enriched onto the C18 short pretreatment column by 0.05 M phosphate
      buffer (pH 7.7), while proteins and endogenous hydrophilic substances in plasma
      were washed off to waste. The enriched analytes were then back-flushed onto the
      analytical C18 column, separated by a mixture of 0.05 M phosphate buffer (pH 7.7)
      acetonitrile (88:12, v/v) and detected by the ultraviolet absorbance at 254 nm.
      Recoveries from spiked plasma were quantitative, and the coefficients of
      variation were below 4%. The lower detection limits in plasma were 10 ng/ml for
      both I and II. Concentrations of I and II in plasma determined by the present
      method were in good agreement with those obtained by the conventional
      deproteinization method.

PMID- 1400739
TI  - High-performance liquid chromatographic determination of 3,5-dimethylhippuric
      acid in the occupational exposure to trimethylbenzenes.
AB  - A high-performance liquid chromatographic method for the measurement of urinary
      3,5-dimethylhippuric acid (3,5-DMHA) in the human biological monitoring of the
      occupational exposure to trimethylbenzenes has been developed. 3,5-DMHA was
      extracted from urine with ethyl acetate. The organic phase was dried under vacuum
      and the resultant product, dissolved in the mobile phase, was analysed by an
      isocratic system and a programmable photodiode-array detector adjusted to 205 nm.
      The mobile phase was water-acetonitrile (80:20, v/v) containing 0.1% acetic acid.
      3,5-DMHA was chromatographed on a reversed-phase Supelco C18 column (3 microns;
      15 cm x 0.46 cm I.D.), and identified by its retention time and ultraviolet
      spectrum. Quantitation was performed by peak area. The detection limit of the
      method is 30 ng/ml and the recovery and the accuracy are 96%.

PMID- 1400740
TI  - Extractionless determination of diclofenac sodium in serum using reversed-phase
      high-performance liquid chromatography with fluorimetric detection.
AB  - The author describes a method of using reversed-phase high-performance liquid
      chromatography with fluorimetric detection for the assay of diclofenac sodium in
      serum. The method is sensitive down to 20 ng/ml (250-microliters loop). Elution
      is at pH 6.2 with methanol in 0.05 M phosphate buffer (43:57, v/v) on a 25-cm
      Spherisorb S5 ODS2 column. Detection is at an excitation wavelength of 282 nm and
      an emission wavelength of 365 nm. Serum sample size is 100 microliters. Sample
      protein, to which diclofenac is highly bound, is first denatured by heat and then
      with methanol to release the diclofenac prior to centrifugation and injection of
      100 microliters (or 250 microliters) of the clear supernatant. Harmol, with
      similar fluorescence and polarity characteristics to diclofenac, is a
      satisfactory internal standard. At the 1 micrograms/ml level intra-sample
      reproducibility is better than 2%, whilst inter-sample reproducibility is 4.6%.
      Detector response is linear from 40 ng/ml to 20 micrograms/ml (100-microliters
      loop).

PMID- 1400741
TI  - Method for the quantitation of iodothyronines in body tissues and fluids using
      high-performance liquid chromatography.
AB  - The separation and quantitation of iodotyrosines and iodothyronines [3-monoiodo-L
      tyrosine, 3,5-diiodo-L-tyrosine, 3,5-, 3,3' and 3',5'-diiodo-L-tyronines, 3,5,3'
      triiodo-L-thyronine (T3), reverse 3,3',5'-triiodo-L-thyronine and 3,3',5,5'
      tetraiodo-L-thyronine (T4)] from animal tissues (brain, liver and serum) by a new
      high-performance liquid chromatographic (HPLC) method is described. Rats were
      infused with iso-osmotic sodium chloride containing 100 microM phloretin to block
      deiodination. The tissues were extracted using differential pH values to separate
      other amines from the amine containing iodothyroid hormones. Aliquots of tissue
      extracts (25-100 microliters) were reacted overnight with 5
      dimethylaminonaphthalene-1-sulfonyl chloride and their iodotyrosine and
      iodothyronine content determined by HPLC utilizing fluorimetric detection.
      Resolution of the individual compound peaks was achieved by gradient elution with
      a 3.0 mM H3PO4 buffer. Greater sensitivity has been achieved (less than 1.0
      pmol/g) utilizing fluorescence rather than ultraviolet absorbance for the
      quantitation of these iodinated compounds. The method is superior also to other
      methods in that recoveries, based on those of 125I-labelled T4 and T3, were 89
      97%.

PMID- 1400742
TI  - Sensitive assay for triazolam in plasma following low oral doses.
AB  - At low doses of triazolam currently recommended increased assay sensitivity is
      required for measurement of low plasma concentrations. A highly sensitive
      capillary gas chromatographic analytical method with a limit of detection of 0.02
      ng/ml was developed and used to describe the pharmacokinetics of triazolam
      following the oral intake of 0.125, 0.250 and 0.375 mg. Six male subjects were
      studied with blood sampling at the following times: 0, 15, 30 and 45 min and 1,
      1.5, 2.0, 2.5, 3, 4, 5, 6 and 8 h. The mean pharmacokinetic parameters for the
      three doses, respectively, were as follows: half-life, 2.7 +/- 0.4, 3.2 +/- 0.5
      and 3.2 +/- 0.6 h; apparent oral clearance, 302.3 +/- 59.0, 260.2 +/- 67.9 and
      328.6 +/- 77.8 ml/min; apparent volume of distribution, 64.3 +/- 9.6, 62.0 +/-
      12.6 and 73.3 +/- 7.7 l; time to maximum concentration, 0.7 +/- 0.2, 0.6 +/- 0.1
      and 0.8 +/- 0.3 h; maximum concentration, 2.2 +/- 0.3, 4.3 +/- 0.6 and 5.0 +/-
      0.5 ng/ml; and the area under the concentration-time curve (AUC) up to 8 h, 6.8
      +/- 1.2, 16.8 +/- 2.9 and 19.6 +/- 3.5 ng/ml h; and AUC extrapolated to infinity,
      8.5 +/- 1.7, 21.4 +/- 4.4 and 26.3 +/- 7.2 ng/ml h. There were no significant
      differences in the half-life, clearance, volume of distribution and time to
      maximum concentration among the three doses. The AUC was significantly different
      on the three occasions and was linearly correlated with dose: r = 0.64 (p less
      than 0.005).

PMID- 1400743
TI  - Simple and high-yield purification of urine protein 1 using immunoaffinity
      chromatography: evidence for the identity of urine protein 1 and human Clara cell
      10-kilodalton protein.
AB  - A simple and high-yield purification procedure for urine protein 1 (UP1) using
      anti-UP1 immunoaffinity chromatography is described. Pure UP1 was obtained in a
      final yield of 60.2%, and observed as a single electrophoretic band and as a
      single peak on reversed-phase high-performance liquid chromatography. The N
      terminal amino acid residue of UP1 was found to be glutamic acid, contrary to
      what was reported previously. Furthermore, the N-terminal sequence of UP1 up to
      53 amino acids was confirmed to be identical with that of mature human Clara cell
      10-kilodalton protein, which inhibits phospholipase A2 activity.

PMID- 1400744
TI  - Determination of nicotinamide-adenine dinucleotide and thiazole-4-carboxamide
      adenine dinucleotide in human leukocytes by reversed-phase high-performance
      liquid chromatography.
AB  - A high-performance liquid chromatographic assay for cellular nicotinamide-adenine
      dinucleotide and thiazole-4-carboxamide-adenine dinucleotide is presented that is
      appropriate for analysis of these dinucleotides in extracts of Ficoll-purified
      human leukemic cells. The separation, which is effected by reversed-phase
      chromatography, is highly reproducible and the limit of quantitation is as low as
      10-15 pmol. The stability of these compounds in neutralized perchloric acid
      extracts is addressed and the applicability of the procedure to clinical
      specimens is demonstrated.

PMID- 1400745
TI  - pH titration curves of the desialylated human alpha 1-acid glycoprotein variants
      by combined isoelectrofocusing-electrophoresis: utilization in the development of
      a fractionation method for the protein variants by chromatography on immobilized
      metal affinity adsorbent.
AB  - Using a two-dimensional isoelectrofocusing (IEF)-electrophoresis technique, the
      pH titration curves of the three main desialylated variants (F1, S and A) of
      human alpha 1-acid glycoprotein (AAG) were studied to assist in the development
      of a fractionation method for the AAG variants. For this purpose, different AAG
      samples, each corresponding to one of the three main phenotypes of the protein
      (F1S/A, F1/A and S/A), were first purified by chromatographic separation of
      individual human plasma samples on immobilized Cibacron Blue F3G-A. The purified
      AAG samples were then disialylated and their heterogeneity was checked by
      analytical IEF. The pH-mobility curves of the desialylated AAG samples were
      displayed in polyacrylamide gel slabs, under a constant set of experimental
      conditions, by carrying out electrophoresis of the protein samples
      perpendicularly to two stationary pH gradients: a large gradient (pH 3.5-9.5) and
      a narrow gradient (pH 5-8). The curves showed that all the desialylated variants
      of AAG exhibited small charge differences and moved closely together between
      about pH 3.5-5.5 and pH 7.5-9.5. However, the variants were found to show
      microheterogeneity in their total charge between about pH 5.5 and 7.5 due to the
      titrated ionizable groups involved along this pH zone. This microheterogeneity
      was assumed to be accounted for by the existence of differences between the
      titratable histidyl residues of the AAG variants. Consequently, the interactions
      of the variants with immobilized transition metal ions were studied at pH 7,
      using affinity chromatography on an iminodiacetate Sepharose-Cu(II) gel. It was
      found that the A variant was strongly bound by immobilized Cu(II) ions, whereas
      the F1 and S variants interacted non-specifically with the immobilized ligand.
      This finding allowed the development of a rapid and effective fractionation
      method for desialylated AAG into its A and F1 or S variants, depending on the AAG
      phenotype, by chromatography on an immobilized affinity Cu(II) adsorbent. The
      quantitative relationships between immobilized Cu(II) ions and desialylated AAG
      (the apparent association constant and gel protein-binding capacity) were also
      determined using a non-chromatographic equilibrium binding technique.

PMID- 1400746
TI  - Solid-phase extraction with supercritical fluid elution as a sample preparation
      technique for the ultratrace analysis of flavone in blood plasma.
AB  - A new sample preparation technique, solid-phase extraction with supercritical
      fluid elution, was developed for the selective isolation of ultratrace levels of
      drugs from plasma. Plasma samples spiked with a drug were applied to
      octadecylsilane cartridges and the cartridges were then washed, briefly dried and
      directly fitted into cells for subsequent supercritical fluid elution. The
      absolute recovery was studied by using a radiolabeled model compound. The
      extraction selectivity was examined by chromatographing the extracts with a
      reversed-phase high-performance liquid chromatographic method with ultraviolet
      detection. The effects of extraction pressure and the length of capillary
      restrictors on drug recovery were examined in order to determine the optimal
      conditions for supercritical fluid elution. The performance of the method was
      compared to that of conventional solid-phase extraction in terms of recovery,
      selectivity, precision and accuracy of analysis. Flavone was used as the model
      compound and dog plasma as the biological matrix for these studies.

PMID- 1400747
TI  - Detection of benzo[a]pyrene sulfate and glucuronide conjugates in cell culture
      medium by directly coupled microbore high-performance liquid chromatography-fast
      atom bombardment mass spectrometry.
AB  - An improved method is described for detecting glucuronide and sulfate conjugates
      of benzo[a]pyrene in medium from cell cultures treated with benzo[a]pyrene. This
      method is based on a microbore high-performance liquid chromatograph directly
      coupled to a high-resolution continuous-flow fast atom bombardment mass
      spectrometer. Sulfate and glucuronide conjugates, as well as some structural
      isomers of glucuronide conjugates, were fully separated by the reversed-phase
      microbore high-performance liquid chromatography conditions used in this study.
      Since the method does not rely on the use of radiolabeled materials, it may be
      used to detect conjugates of a wide variety of hydrocarbons. The high sensitivity
      and selectivity of the method were demonstrated by detecting conjugates in the
      media of cell cultures derived from mice, hamsters and humans.

PMID- 1400748
TI  - Determination of tannic acid and its phenolic metabolites in biological fluids by
      high-performance liquid chromatography.
AB  - A method for the identification and determination of tannic acid and its phenolic
      metabolites in biological fluids by high-performance liquid chromatography was
      developed. Tannic acid and four phenolic compounds, namely gallic acid,
      pyrogallol, 4-O-methylgallic acid and ellagic acid, were successfully extracted
      from the biological fluids by using ethyl acetate at acidic conditions. Gallic
      acid, pyrogallol and 4-O-methylgallic acid were found in the sheep urine, gallic
      acid, 4-O-methylgallic acid and ellagic acid in plasma, and gallic acid and
      ellagic acid in abomasal fluid after abomasal dosing of tannic acid. Tannic acid
      was found in the plasma apart from the abomasal fluid into which it was
      administered. The concentrations of tannic acid, gallic acid, pyrogallol, 4-O
      methylgallic acid and ellagic acid in plasma, abomasal fluid and urine were
      measured. This method could be applied to measurement of other hydrolysable
      tannins and their phenolic metabolites in biological materials.

PMID- 1400749
TI  - Validation of the simultaneous determination of methylprednisolone and
      methylprednisolone acetate in human plasma by high-performance liquid
      chromatography.
AB  - A reversed-phase high-performance liquid chromatographic procedure was developed
      that accurately quantitates methylprednisolone (MP) and methylprednisolone
      acetate (MPA) in human plasma over the range 2.00-50.0 ng/ml. The internal
      standard, fluorometholone, was added to an aliquot of sodium fluoride-potassium
      oxalate-derived plasma. Samples were prewashed with hexane and extracted twice
      with methylene chloride. The extracts were dried with anhydrous sodium sulfate,
      centrifuged, and the organic layer separated and dried under nitrogen. The
      samples were reconstituted in mobile phase and washed an additional time with
      hexane before 100 microliters were injected onto a Beckman/Altex Ultrasphere ODS
      column with ultraviolet absorbance detection at 254 nm. Composition of the mobile
      phase was acetonitrile-water-glacial acetic acid (33:62:5, v/v/v). Calibration
      curves were obtained by unweighted, linear regression of peak-height ratios of MP
      (or MPA)/internal standard versus theoretical concentrations of MP or MPA using a
      Hewlett-Packard 3357 Laboratory Automation System. Extraction efficiencies for MP
      and MPA over the linear range were 86.4 and 84.7%, respectively. This method was
      successfully implemented for the analysis of specimens generated from a single
      dose bioavailability and safety study for a new formulation of Depo-Medrol
      sterile aqueous suspension.

PMID- 1400750
TI  - High-performance liquid chromatographic separation of malondialdehyde
      thiobarbituric acid adduct in biological materials (plasma and human cells) using
      a commercially available reagent.
AB  - The assay of malondialdehyde (MDA) is widely used in clinical chemistry
      laboratories to investigate lipid peroxidation in oxidative pathologies. In the
      present work, the thiobarbituric acid (TBA) reaction was carried out on plasma,
      human erythrocytes and fibroblasts. The reagents used were those of the
      fluorimetry MDA kit manufactured by Sobioda. We have defined the application of
      this kit to high-performance liquid chromatography. This adaptation satisfied the
      criteria of good analytical practice. The detection limit was 2.5 pmol per
      injection. The retention time of the MDA-TBA2 peak (4.96 +/- 0.07 min) led to
      excellent resolution of the complex. The within-assay (6-12%) and between-assay
      (11-12%) precisions were satisfactory. The analytical recovery of MDA after
      spiking samples of human plasma with tetraethoxypropane standards varied from 70
      to 100%. The mean lipoperoxide concentration determined in 32 healthy adults (20
      40 years) was 1.04 +/- 0.23 mumol l-1 in plasma. Applied to the erythrocytes of
      fifteen laboratory workers, the method furnished physiological values of 0.59 +/-
      0.21 mumol l-1. Concentrations were significantly higher in chronic renal
      dialysis patients (4.15 +/- 2.35 mumol l-1. The MDA content of fibroblasts
      cultured in standard medium was 0.38 +/- 0.04 mumol per g of protein and
      increased (5.78 +/- 1.38 mumol per g of protein) if the cells were grown in an
      iron-enriched medium. This accurate high-performance liquid chromatographic
      method for detection of MDA is the first one which can be applied to plasma, red
      blood cells and cultured cells. This technique will prevent false positives and
      should make inter-laboratory comparisons possible.

PMID- 1400751
TI  - Determination of enantiomers of 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2
      yl]methylpiperidine hydrochloride (E2020), a centrally acting acetylcholine
      esterase inhibitor, in plasma by liquid chromatography with fluorometric
      detection.
AB  - Two high-performance liquid chromatographic methods for the determination of
      enantiomers of E2020, 1-benzyl-4-[(5,6-dimethoxy-1-indanon)2-yl]methylpiperidine
      (I) hydrochloride, in rat plasma have been developed. The first method involves
      chiral separation of I on an ovomucoid-bonded column, and native fluorescence
      detection of I with excitation at 318 nm and emission at 390 nm. The fluorometric
      detection is without interference from background components and is about five
      times more sensitive than ultraviolet detection at 271 nm. The method was
      successfully applied to monitoring the racemization of each enantiomer of I in
      buffer solutions and in rat plasma. The second method involves separation of I
      from background components of rat plasma on an achiral column, collection of the
      I fraction into a sample loop, concentration or I to a trap column, transfer of I
      to a chiral column, resolution of the enantiomers of I on the chiral column and
      fluorometric detection of the enantiomers of I with excitation at 318 nm and
      emission at 390 nm. The detection limits of I and each enantiomer of I were 1 and
      1 ng/ml, respectively, with a 200-microliters injection of deproteinized plasma
      samples.

PMID- 1400752
TI  - Detection of methandienone (methandrostenolone) and metabolites in horse urine by
      gas chromatography-mass spectrometry.
AB  - The metabolic transformation of methandienone (I) in the horse was investigated.
      After administration of a commercial drug preparation to a female horse (0.5
      mg/kg), urine samples were collected up to 96 h and processed without enzymic
      hydrolysis. Extraction was performed by a series of solid-liquid and liquid
      liquid extractions, thus avoiding laborious purification techniques. For analysis
      by gas chromatography-mass spectrometry, the extracts were trimethylsilylated.
      Besides the parent compound I and its C-17 epimer II, three monohydroxylated
      metabolites were identified: 6 beta-hydroxymethandienone (III), its C-17 epimer
      (IV) and 16 beta-hydroxymethandienone (V). In addition, three isomers of 6
      beta,16-dihydroxymethandienone (VIa-c) were discovered. Apparently, reduction of
      the delta 4 double bond of 16 beta-hydroxymethandienone (V) in the horse yields
      16 beta,17 beta-dihydroxy-17 alpha-methyl-5 beta-androst-1-en-3-one (VII).
      Reduction of the isomers VIa-c results in the corresponding 6 beta,16,17
      trihydroxy-17-methyl-5 beta-androst-1-en-3-ones (VIIIa-c). The data presented
      here suggest that screening for the isomers of VI and VIII, applying the selected
      ion monitoring technique, will be the most successful way of proving
      methandienone administration to a horse.

PMID- 1400753
TI  - Identification of urinary acylcarnitines using gas chromatography-mass
      spectrometry: preliminary clinical applications.
AB  - Many disorders of organic acid metabolism are associated with abnormalities in
      the levels of acylcarnitines excreted in urine. Profiling of urinary
      acylcarnitines allows diagnosis and characterisation of many acidurias and
      acidemias, monitoring dietary treatment of such patients, and elucidation of the
      metabolism of some exogenous acidic compounds. Urine (ca. 0.5 ml) was subjected
      to a simple work-up by ion-exchange chromatography, and the isolated
      acylcarnitines were derivatized by cyclization in 35 min to give volatile
      lactones that are compatible with gas chromatography-mass spectrometry using
      electron or chemical ionization. The feasibility of this new and affordable
      procedure has been confirmed by identifying urinary acylcarnitines in cases of
      medium-chain acyl-coenzyme A dehydrogenase deficiency, propionic acidemia and
      isovaleric acidemia.

PMID- 1400754
TI  - Simple and sensitive determination of diacetyl and acetoin in biological samples
      and alcoholic drinks by gas chromatography with electron-capture detection.
AB  - Acetoin was quantitatively oxidized into diacetyl by Fe3+ in 1 M perchloric acid.
      The reaction of diacetyl with 4,5-dichloro-1,2-diaminobenzene afforded 6,7
      dichloro-2,3-dimethylquinoxaline (DCDMQ), which was extracted by benzene
      containing aldrin (25 ng/ml) as an internal standard, and determined by gas
      chromatography with electron-capture detection. The method is very simple and
      sensitive. The detection limit of DCDMQ (either diacetyl or acetoin) was 10
      fmol/microliters of the benzene extract, and the determination limit of DCDMQ
      (either diacetyl or acetoin) was 50 fmol/microliters of the extract. Both acetoin
      and diacetyl could be determined in 0.1 ml of normal human urine or blood, and
      both were found in rat liver, kidney and brain. The method was also applied to
      the determination of acetoin and diacetyl in alcoholic drinks.

PMID- 1400755
TI  - Thermospray liquid chromatography-mass spectrometry of corticosteroids.
AB  - A high-performance liquid chromatographic method was developed for thermospray
      mass spectrometric analysis of steroidal hormones. Using a Nova-Pak C18 reversed
      phase column and isocratic elution with a solvent comprised of 25 mM ammonium
      formate in 30% acetonitrile, corticosteroids were separated within 10 min. This
      solvent also permitted ultraviolet absorbance detection down to 220 nm with low
      nanogram sensitivity. The use of acetonitrile was favourable for thermospray mass
      spectrometric analysis because mass spectra were obtained with a pseudomolecular
      ion as the base peak. A combination of liquid chromatography, ultraviolet
      absorbance detection and thermospray mass spectrometry provided a sensitive and
      reliable method for unequivocal confirmation of the presence of steroidal drugs
      in equine urine.

PMID- 1400756
TI  - Determination of conjugated bile acids in human urine by high-performance liquid
      chromatography with chemiluminescence detection.
AB  - A qualitative and quantitative analysis of the conjugated 1 beta- and 6 alpha
      hydroxy bile acids, including common bile acids, in human urine using high
      performance liquid chromatography with chemiluminescence detection is described.
      After extraction of urine with C18 silica cartridges, the bile acids were
      separated into non-conjugated, glycine, taurine and sulphate fractions by ion
      exchange chromatography on a lipophilic gel. Solvolysis of the sulphate was
      carried out by treatment with trifluoroethanol in acetone containing hydrochloric
      acid, and the liberated amino acid conjugates were fractionated again. The
      individual bile acids were separated on a reversed-phase C18 column (Bile Pak
      II), with detection by an immobilized 3 alpha-hydroxysteroid dehydrogenase enzyme
      reactor and chemiluminescence reaction of the generated NADH using 1-methoxy-5
      methylphenazinium methylsulphate-isoluminol-microperoxidase system. The assay
      method showed the detection limits ranging from 8 to 250 pmol for the bile acids
      tested. Analysis of urine samples obtained from newborns, non-pregnant women and
      women in late pregnancy showed a large difference in bile acid composition and
      conjugation mode, suggesting that bile acid metabolism is different during fetal
      and neonatal periods.

PMID- 1400757
TI  - Use of biospecific interactions of collagen, fibronectin and their fragments in
      affinity chromatography.
AB  - Various aspects of the application of fibronectin-collagen biospecific
      interactions in affinity chromatography are described. A new biospecific method
      for one-stage isolation of collagen peptides containing fibronectin-binding sites
      is proposed. The alpha 1 CB7-peptide of type-I collagen cyanogen bromide cleavage
      was isolated by means of affinity chromatography on adsorbents containing an
      immobilized gelatin-binding domain (45,000 relative molecular mass) of
      fibronectin. The method gives highly purified preparations of alpha 1 CB7
      peptide. This peptide, as well as some other collagen molecular fragments (alpha
      chains, beta-components, alpha 1 CB8-peptide), were immobilized on Sepharose, and
      the properties of such affinity adsorbents obtained were studied. Adsorbents with
      immobilized alpha-chains and alpha 1 CB7-peptide had a fibronectin-binding
      capacity 1.5-2.0 times higher than commercial gelatin-Sepharose. Large-scale
      production of highly purified fibronectin from human plasma, using affinity
      chromatography on immobilized individual alpha-chains of collagen, was developed.

PMID- 1400758
TI  - Use of a carrier for quantitation of a new dihydropyridine calcium antagonist
      (OPC-13340) in human plasma by highly sensitive gas chromatography with negative
      ion chemical ionization mass spectrometry.
AB  - A sensitive gas chromatographic-mass spectrometric method for the quantitation of
      (+/-)-methyl 3-phenyl-2(E)-propenyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)
      3,5-pyridinedicarboxylate (OPC-13340, I), a new dihydropyridine calcium
      antagonist with a potent and long-acting antihypertensive and antianginal effect,
      was developed in order to elucidate its pharmacokinetics. Dihydropyridine calcium
      antagonist have been usually quantifed by this technique in the negative-ion
      chemical ionization mode. However, direct application of this method to quantify
      trace amounts of I in biological fluids completely failed, owing to its
      adsorption on the column and oxidation of its dihydropyridine ring. Human plasma
      containing I and (+/-)-[2H3]methyl 3-phenyl-2(E)-propenyl 1,4-dihydro-2,6
      dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (II), the internal standard,
      was extracted with n-hexane-diethyl ether under weakly basic conditions (pH 8).
      In order to prevent adsorption of the compounds on the column, (+/-)-[2H5]ethyl 3
      phenyl-2(E)-propenyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5
      pyridinedicarboxylate (III), an analogue of I, was added to the extracts as a
      carrier. In addition, this carrier was also effective in preventing the oxidation
      of I. The quantitation limit of I in human plasma by this method was found to be
      less than 30 pg/ml. Thus, the method is sufficiently sensitive to study the
      pharmacokinetics of I in humans.

PMID- 1400759
TI  - Nanogram level quantitation of oxycodone in human plasma by capillary gas
      chromatography using nitrogen-phosphorus selective detection.
AB  - A sensitive and specific capillary gas chromatographic assay is reported for the
      quantitation of oxycodone in human plasma. The technique involves a single
      extraction of oxycodone and internal standard (hydrocodone) from plasma by
      toluene containing 1% isopropanol. Separation is achieved on a methyl silicone
      (HP-1) fused-silica capillary column (25 m x 0.2 mm I.D., 0.33 microns film
      thickness) and detection is by nitrogen-phosphorus selective mode. The minimum
      quantifiable limit is 1.8 ng/ml using 2 ml of plasma. The method is applicable to
      characterize the plasma profile of oxycodone in humans after a single oral 5-mg
      oxycodone hydrochloride tablet.

PMID- 1400760
TI  - Gas chromatographic headspace analysis of sevoflurane in blood.
AB  - We have developed a rapid, simple and precise gas chromatographic headspace
      analysis for sevoflurane in blood which circumvents problems associated with the
      high volatility and low blood/gas partition coefficient of this anesthetic drug.
      Blood standards are easily prepared by volumetric addition of a saturated aqueous
      solution of sevoflurane. Likewise, internal standardization is achieved using a
      saturated aqueous solution of halothane. Chromatographic conditions are similar
      to those commonly used for the analysis of blood ethanol. A simple method is also
      described for the preparation of stable and precise, aliquots of quality control
      materials for this assay.

PMID- 1400761
TI  - Allosteric and competitive displacement of drugs from human serum albumin by
      octanoic acid, as revealed by high-performance liquid affinity chromatography, on
      a human serum albumin-based stationary phase.
AB  - A chiral stationary phase for high-performance liquid chromatography, based upon
      immobilized human serum albumin (HSA), was used to investigate the effect of
      octanoic acid on the simultaneous binding of a series of drugs to albumin.
      Octanoic acid was found to bind with high affinity to a primary binding site,
      which in turn induced an allosteric change in the region of drug binding Site II,
      resulting in the displacement of compounds binding there. Approximately 80% of
      the binding of suprofen and ketoprofen to HSA was accounted for by binding at
      Site II. Octanoic acid was found to also bind to a secondary site on HSA, with
      much lower affinity. This secondary site appeared to be the warfarin-azapropazone
      binding area (drug binding Site I), as both warfarin and phenylbutazone were
      displaced in a competitive manner by high levels of octanoic acid. The
      enantioselective binding to HSA exhibited by warfarin, suprofen and ketoprofen
      was found to be due to differential binding of the enantiomers at Site I; the
      primary binding site for suprofen and ketoprofen was not enantioselective.

PMID- 1400762
TI  - Stereospecific high-performance liquid chromatographic assay of pirprofen
      enantiomers in rat plasma and urine.
AB  - A stereospecific high-performance liquid chromatographic method was developed for
      the assay of pirprofen enantiomers in rat plasma and urine. Following addition of
      internal standard (ketoprofen) and acidifier (L-ascorbic acid) to biological
      fluids, pirprofen was extracted into an isopropanol-isooctane (5:95) mixture.
      Diastereomers of pirprofen enantiomers, which were formed using L-leucinamide,
      were separated on a reversed-phase column with ultraviolet detection at 275 nm
      using 0.06 M KH2PO4-acetonitrile-triethylamine (64:36:0.1) as mobile phase. The
      limit of quantitation was 0.1 microgram/ml for each enantiomer, based on 100
      microliters of rat plasma. No spontaneous oxidation of pirprofen to its pyrrole
      metabolite occurred during sample preparation and analysis. In three female rats
      which were dosed with 10 mg/kg racemic pirprofen orally, plasma concentrations of
      the enantiomers could be followed for 24 h. Pirprofen enantiomers in plasma were
      virtually unconjugated, and negligible concentrations of pyrrole metabolites were
      observed. Less than 10% of the total dose was recovered in urine as intact drug
      and its glucuroconjugates. The assay was found suitable for the study of the
      pharmacokinetics of pirprofen enantiomers in the rat.

PMID- 1400763
TI  - Simultaneous quantitative determination of naproxen, its metabolite 6-O
      desmethylnaproxen and their five conjugates in plasma and urine samples by high
      performance liquid chromatography on dynamically modified silica.
AB  - The glucuronides of the anti-inflammatory drug naproxen and its metabolite 6-O
      desmethylnaproxen have been produced on a preparative scale by enzymatic
      synthesis. 6-O-Desmethylnaproxen, the glycine conjugate of naproxen and the O
      sulphate of 6-O-desmethylnaproxen were prepared by chemical synthesis. Naproxen
      and the purified metabolite and conjugates were used as standards for the
      analytical investigation of the metabolic pattern of naproxen in humans. A
      reversed-phase high-performance liquid chromatographic method based on bare
      silica dynamically modified with cetyltrimethylammonium ions has been developed.
      The system was optimized to give a separation of naproxen, 6-O-desmethylnaproxen
      and five conjugates. Using this method it is also possible to deduce the
      relationship between the amount of the intact ether-glucuronide and acyl
      glucuronide of 6-O-desmethylnaproxen.

PMID- 1400764
TI  - Fast systematic approach for the determination of drugs in biological fluids by
      fully automated high-performance liquid chromatography with on-line solid-phase
      extraction and automated cartridge exchange. Application to cebaracetam in human
      urine.
AB  - A fast stepwise systematic approach for the conversion of conventional reversed
      phase high-performance liquid chromatographic (HPLC) assays involving liquid
      liquid extraction of biological fluids into fully automated HPLC assays using
      solid-phase extraction and cartridge exchange is described. The suitability of
      this procedure is demonstrated for the determination of cebaracetam in human
      urine.

PMID- 1400765
TI  - Comparison of two extraction procedures for urinary organic acids prior to gas
      chromatography-mass spectrometry.
AB  - We have compared a new isolation procedure for urinary organic acids using strong
      anion-exchange columns with a solvent partition (ethyl acetate) method. Urinary
      samples from two healthy children and from nine children with organic acidurias
      were analysed by both procedures. Although the solid-phase extraction is more
      efficient for polyhydroxy acids, some polar acids, and some glycine derivatives,
      clinically important compounds such as oxalic, methylcitric, pyruvic, glyoxylic
      and 2-ketoglutaric acids, are not recovered or are only poorly recovered.
      However, both procedures may be used as a routine method for the diagnosis of the
      organic acidurias included in this study.

PMID- 1400766
TI  - Analysis of novel imidazoles from isolated perfused rabbit heart by two high
      performance liquid chromatographic methods.
AB  - The paper reports two analytical high-performance liquid chromatographic methods
      to detect and quantify cardiac-derived histidyl derivatives. Method A relies on
      relative hydrophobicities as a basis of separation. Method B is an ion-pairing
      method in which the compounds are eluted in an entirely different order.
      Fractions collected from method A have been co-eluted in admixture in method B
      with authentic reference compounds. Thus the existence of the following imidazole
      ring-containing compounds derived from heart have been confirmed: N
      acetylhistidine, N-acetyl-1-methylhistidine, N-acetylcarnosine, N
      acetylhomocarnosine, homocarnosine, anserine, carnosine, balenine. Compounds were
      found in both tissue samples and perfusates.

PMID- 1400767
TI  - Simultaneous determination of cotinine and trans-3'-hydroxycotinine in human
      serum by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method with ultraviolet photometric
      detection has been developed for the quantitation of cotinine and trans-3'
      hydroxycotinine in human serum. A solid-phase extraction procedure was performed
      for the analytes and the internal standard, N-ethylnorcotinine, before
      chromatography. The use of a 30-cm reversed-phase column and a mobile phase of
      water-methanol-0.1 M sodium acetate-acetonitrile (67:24.5:6.5:2, v/v), pH 4.3,
      prevented the co-elution of caffeine with cotinine. The limit of quantitation
      observed with this method was 5 ng/ml for both cotinine and trans-3'
      hydroxycotinine. The present method proved useful for the determination of serum
      levels of these metabolites, correlating with nicotine daily intake.

PMID- 1400768
TI  - Simultaneous determination of (R)- and (S)-naproxen and (R)- and (S)-6-O
      desmethylnaproxen by high-performance liquid chromatography on a Chiral-AGP
      column.
AB  - A high-performance liquid chromatographic method for the simultaneous
      determination of both enantiomers of naproxen and its metabolite 6-O
      desmethylnaproxen has been developed. The separation is performed on a column
      containing alpha 1-acid glycoprotein as the chiral selector. The method has been
      used for the determination of the enantiomeric purity of the drug substance and
      the metabolite, and for the simultaneous determination of all four compounds in
      biological fluids.

PMID- 1400769
TI  - High-performance liquid chromatographic method for the determination of
      mangiferin, likviritin and dihydroquercetin in rat plasma and urine.
AB  - The use of reversed-phase high-performance liquid chromatography for the
      determination of the biologically active plant phenolic compounds mangiferin,
      likviritin and dihydroquercetin is described. Perchloric acid (35%) was used for
      deproteinization in the case of mangiferin and likviritin, and acidified methanol
      for dihydroquercetin. Detection was performed at 254, 275 and 290 nm for
      mangiferin, likviritin and dihydroquercetin in plasma, and 365, 312 and 290 nm in
      urine, respectively. The limit of detection was 0.2 micrograms/ml for plasma and
      0.5 micrograms/ml for urine.

PMID- 1400770
TI  - High-performance liquid chromatographic determination of imidocarb in cattle
      kidney with cation-exchange clean-up.
AB  - A high-performance liquid chromatographic (HPLC) method for the determination of
      the antiprotozoal agent imidocarb in cattle kidney is developed. The drug is
      extracted from tissue with acetone in the presence of base. The extract is
      partitioned between saturated salt and chloroform and the organic layer
      evaporated to dryness. Clean-up is by cation-exchange solid-phase extraction on a
      carboxylic acid column. HPLC analysis is carried out on a Spherisorb S3W-PC18
      column with ultraviolet detection at 260 nm. Average recoveries at the 0.05 and
      0.01 mg kg-1 levels are 77.5 and 76.3%, respectively. The limit of detection is
      0.001 mg kg-1.

PMID- 1400771
TI  - Determination of picotamide in human plasma and urine by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic method for the determination of
      picotamide in human plasma and urine is described. After addition of an internal
      standard (bamifylline), the plasma and urine samples were subjected to liquid
      liquid extraction and clean-up procedures. The final extracts were evaporated to
      dryness and the resulting residues were reconstituted in 100 microliters of
      methanol-water (50:50, v/v) and chromatographed on a LiChrosorb RP-SELECT B
      reversed-phase column coupled to an ultraviolet detector monitored at 230 nm.
      Chromatographic analysis takes about 10 min per sample. The assay was linear over
      a wide range and has a limit of detection of 0.005 and 0.1 micrograms/ml in
      plasma and urine, respectively. It was selective for picotamide, accurate and
      robust and thus suitable for routine assays after therapeutic doses of
      picotamide.

PMID- 1400772
TI  - Rapid determination of propyphenazone in plasma by high-performance liquid
      chromatography.
AB  - A rapid and simple high-performance liquid chromatographic assay for the
      determination of propyphenazone in plasma is described. Phenylbutazone was used
      as the internal standard. Plasma proteins were precipitated with acetonitrile
      before injection onto a 3-microns Supelcosil LC-18 column. The mobile phase,
      ethanol containing 0.2% (v/v) heptylamine-0.005 M potassium dihydrogenphosphate
      (30:70, v/v), was used at a flow-rate of 1.3 ml/min. The quantitation was
      performed by ultraviolet detection at a wavelength of 270 nm. The chromatographic
      time was 7 min. The within- and between-day coefficients of variation were less
      than 6% and the recoveries close to 100% for concentrations between 0.4 and 22
      mumol/l. The limit of quantitation was 0.4 mumol/l (ca. 100 ng/ml).

PMID- 1400773
TI  - Determination of "free" glycerol in human serum reference materials by isotope
      dilution gas chromatography-mass spectrometry.
AB  - Serum free glycerol analyses are an important part of the preparation and
      evaluation of human serum reference materials used for the quality assurance of
      triglyceride assays. However, enzymatic kits for free glycerol analysis obtained
      from different vendors have, on occasion, provided different results for a given
      sample. In an effort to establish the "target" glycerol content of selected
      reference materials, we have established a method for the analysis of serum free
      glycerol by using isotope-dilution gas chromatography-mass spectrometry,
      incorporating [1,3-13C2]glycerol as the internal standard. The use of a
      simplified serum extraction and clean-up procedure resulted in (uncorrected)
      recoveries of glycerol averaging about 90% before derivatization, and in
      estimated concentrations for spiked serum pools that corresponded closely to the
      expected values. A comparison of enzymatic and gas chromatographic-mass
      spectrometric results for several reference serum pools suggest that the latter
      method is of value in evaluating and validating routine enzymatic methods for
      free glycerol analysis.

PMID- 1400774
TI  - High-performance liquid chromatographic assay for 1-aminocyclopropanecarboxylic
      acid from plasma and brain.
AB  - A reversed-phase high-performance liquid chromatographic method for the analysis
      of 1-aminocyclopropanecarboxylic acid (ACPC) from plasma or brain tissue is
      described. Samples were deproteinized with perchloric acid, centrifuged,
      alkalinized with potassium hydroxide and recentrifuged. The supernatants were
      derivatized with o-phthaldialdehyde and injected onto a C18 3-microns column (100
      mm x 4 mm I.D.) pumped with 1 ml/min methanol-acetonitrile-0.1 M sodium phosphate
      buffer pH 6.0 (28:5:67, v/v). The retention times for ACPC and the internal
      standard were 15 and 31 min, respectively. The minimum detectable amount of ACPC
      was 0.08 nmol. The extraction recovery of ACPC (2.7-270 nmol) from spiked plasma
      or brain tissue ranged from 88 to 109%. The intra- and inter-day coefficients of
      variation for 27 nmol ACPC were 3.9 and 4.9%, respectively. This method was
      utilized to obtain preliminary pharmacokinetic parameters following ACPC
      administration to mice.

PMID- 1400776
TI  - Quantitative measurement of N-acetyl-L-aspartic acid in urine by gas
      chromatography with negative-ion chemical ionization mass spectrometry.
AB  - A highly specific and sensitive assay for N-acetyl-L-aspartic acid has been
      developed. The trideuterated compound was synthesized and used as an internal
      standard for gas chromatography with negative-ion chemical ionization mass
      spectrometry. Urine samples were acidified and extracted with ethyl acetate, and
      the compounds converted into their pentafluorobenzyl ester derivatives. Under
      these conditions, sub-picogram amounts of the pure derivatives could be detected.
      Thus, only microliter volumes of urine samples have to be processed to achieve
      reliable quantification of "basal" levels of N-acetyl-L-aspartic acid.

PMID- 1400775
TI  - Endogenous synthesis of N-methylsalsolinol, an analogue of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine, in rat brain during in vivo microdialysis with
      salsolinol, as demonstrated by gas chromatography-mass spectrometry.
AB  - N-Methylsalsolinol, an analogue of 1,2,3,6-tetrahydropyridine, is present in the
      brains of patients with Parkinson's disease. To determine the metabolic pathway
      for the synthesis of N-Methylsalsolinol in the brain, salsolinol was perfused
      through the striatum or the substantia nigra of the rat brain by in vivo
      microdialysis. N-Methylsalsolinol was detected in the brain dialysate samples
      during microdialysis with salsolinol using gas chromatography-mass spectrometry
      with selected-ion monitoring. These results demonstrate that endogenous N
      methylation of salsolinol into N-methylsalsolinol occurs in the brain in vivo.

PMID- 1400777
TI  - Determination of urinary beta-phenylethylamine as its N-benzenesulphonamide
      derivative by gas chromatography with flame photometric detection.
AB  - A selective and sensitive method for the determination of urinary beta
      phenylethylamine (PEA) by gas chromatography (GC) has been developed. After
      extraction of the urine sample with n-pentane, PEA was converted into its N
      benzenesulphonamide derivative and then determined by GC with flame photometric
      detection using a DB-1301 capillary column. By using this method, nanogram
      amounts of PEA in urine could be accurately and precisely determined without any
      influence from coexisting substances. Analytical results for the determination of
      PEA in urine samples from normal subjects are presented.

PMID- 1400778
TI  - Quantitation of phenacyl esters of retinal fatty acids by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic (HPLC) method for the separation and
      quantitation of retinal fatty acids containing long-chain polyunsaturated fatty
      acids is described. Fatty acids from frog retinal lipids were converted to the
      corresponding phenacyl derivatives which were separated on a C18 reversed-phase
      column and detected at 242 nm. Molar absorptivities (peak area units/nmol) of up
      to seventeen fatty acid phenacyl derivatives were determined and used for
      quantitation of fatty acids separated by HPLC. Compared with gas chromatography,
      the HPLC method gave a similar molar percent distribution of the fatty acids and
      was twenty to fifty times more sensitive. This HPLC method provides a useful
      means for the study of chemistry and metabolism of long-chain polyunsaturated
      fatty acids in retina and other tissues where amounts of material may be limited
      or recovery of individual components desirable.

PMID- 1400779
TI  - Rapid method to isolate serum amyloid P component from human plasma.
      Characterization of the isolated protein.
AB  - A rapid and reproducible method to isolate serum amyloid P component from healthy
      human plasma has been developed. It uses affinity chromatography on an agarose
      column followed by anion-exchange chromatography. It was found that the isolated
      compound has a significantly different isoelectric point (pI 5.7) from that
      reported previously (pI 4.1). The new data are in good agreement with calculated
      values determined from the amino acid composition of the protein.

PMID- 1400780
TI  - Automated high-performance liquid chromatographic assay for the determination of
      7-ethoxycoumarin and umbelliferone.
AB  - An improved high-performance liquid chromatographic assay is presented for the
      determination of 7-ethoxycoumarin O-deethylase activity. Following a 30-min
      microsomal incubation, 7-ethoxycoumarin, 4-methylumbelliferone (internal
      standard), and the metabolite umbelliferone were extracted with chloroform.
      Separation was achieved with an isocratic mobile phase using a microBondapak
      phenyl (300 mm x 3.9 mm I.D.) analytical column. The effluent was monitored by
      fluorescence detection with an excitation wavelength of 360 nm and an emission
      wavelength of 470 nm. The intra- and inter-assay coefficients of variation were
      10 and 6%, respectively. A detection limit of 0.07 micrograms/ml was achieved,
      making this method suitable for characterizing P-450 activity of human livers.

PMID- 1400781
TI  - Separation and determination of aminohalogenbenzophenones by high-performance
      liquid chromatography with electrochemical detection.
AB  - A high-performance liquid chromatographic method with electrochemical detection
      has been developed for the determination of three aminohalogenbenzophenones: 2
      amino-2',5-dichlorobenzophenone, 2-amino-5-chlorobenzophenone and 2-amino-5-bromo
      2'-fluorobenzophenone, metabolites of benzodiazepinooxazoles and other
      psychotropic drugs. A mobile phase of methanol-water (65:35), containing 5 mM
      KH2PO4 appeared to be the optimal when a 4-microns, 60-A Nova-Pak C18 column and
      a flow-rate of 0.75 ml/min (130 bar) were used. The temperature was optimized at
      30 degrees C. The amperometric detector, equipped with glassy carbon electrode,
      was operated at 1.3 V versus Ag/AgCl in the DC mode. The method was applied to
      the determination of these compounds at two concentration levels: ppm and ppb
      (ng/cm3) using 2-amino-5-chlorobenzophenone as internal standard. The limit of
      determination was 750 pg/ml of biological fluid for each compound, and recoveries
      greater than 97% were obtained for spiked samples of urine and serum, using C18
      Sep-Pak cartridges in the sample clean-up procedure.

PMID- 1400783
TI  - Determination of the catecholamines and serotonin, their precursors tyrosine and
      tryptophan, and their main metabolites in rat brain using reversed-phase high
      performance liquid chromatography with fluorimetric and oxidative amperometric
      detection in series.
AB  - A high-performance liquid chromatographic method for the determination of
      catecholamines and serotonin, their precursors and their main metabolites was
      developed applied to rat cerebellum, hypothalamus, striatum and cortex. A
      fluorimetric and an oxidative amperometric detector were used in series. For both
      detectors, detection limits (25-520 pg) were useful for this application,
      linearity of standards was excellent (average r greater than 0.9997), between-run
      precision for sample analytes was generally acceptable (coefficient of variation
      less than 10% with appreciable concentrations present) and average recoveries of
      standard additions to sample analytes were better than 90%. Particular attention
      was paid to peak identification, including both a thorough treatment of retention
      time agreement of peaks in standards and sample analytes, and a comparison of
      results for the seven compounds amenable to quantitation by both detectors.
      Considerable attention was also given to determining the stability of standards
      and sample analytes under a wide variety of conditions, and practical
      recommendations were made.

PMID- 1400782
TI  - Determination of AJ-3941, a possible agent for the treatment of cerebrovascular
      disorders, in plasma and brain by means of high-performance liquid chromatography
      with fluorescence detection.
AB  - A sensitive and selective high-performance liquid chromatographic method with
      fluorescence detection is described for the determination of AJ-3941 (I), a
      possible agent for the treatment of cerebrovascular disorders, in plasma and
      brain tissue. A simple hexane extraction was used for plasma, and for brain
      homogenate the hexane extract was further purified by solid-phase extraction. The
      determination limit was ca. 3 ng/ml for both plasma (0.5 ml) and 10% (w/v) brain
      homogenate (1 ml). The method was applied to the determination of I in plasma and
      brain samples of experimental animals.

PMID- 1400784
TI  - Simultaneous determination of myocardial nucleotides, nucleosides, purine bases
      and creatine phosphate by ion-pair high-performance liquid chromatography.
AB  - An ion-pair reversed-phase high-performance liquid chromatographic method is
      described for the separation and quantification of myocardial nucleotides,
      nucleosides, their metabolites and creatine phosphate-related compounds in a
      single run. Separation of a standard mixture containing 21 compounds was achieved
      on a 5-microns Hypersil ODS column with a 5-min isocratic elution (buffer: 0.1 M
      NaH2PO4, pH 5.5, containing 5.9 mM tetrabutylammonium hydrogen-sulphate) followed
      by a slow linear gradient to 17% acetonitrile. The method was applied to extracts
      of freeze-clamped rat heart tissue samples as well as to extracts of neonatal rat
      heart cardiomyocytes, and it provided good resolution of high-energy phosphates,
      including creatine phosphate, as well as of their degradation products.

PMID- 1400785
TI  - Determination of vitamin B6 vitamers and pyridoxic acid in biological samples.
AB  - For the determination of vitamin B6 vitamers (pyridoxal phosphate, pyridoxamine
      phosphate, pyridoxal, pyridoxine, pyridoxamine) and 4-pyridoxic acid in
      biological samples such as plasma, cerebrospinal fluid and rat brain regions, a
      sensitive micromethod using high-performance liquid chromatography (HPLC) with
      fluorescence detection in combination with post-column derivatization is
      described. Metaphosphoric acid tissue extracts with deoxypyridoxine as an
      internal standard were injected into the HPLC system with a binary gradient
      elution at a flow-rate of 1.2 ml/min. The excitation wavelength of the
      fluorescence detector was set at 328 nm and the emission wavelength at 393 nm
      with a 15-nm slit width for the photocell. This method allows the assay of
      vitamin B6 vitamers within 30 min in one chromatographic run. The present method
      has been applied extensively for the measurement of vitamin B6 vitamer levels in
      discrete brain regions of small animals, cells in culture and biopsy samples.

PMID- 1400786
TI  - Silver staining of collagen type I after sodium dodecylsulphate polyacrylamide
      gel electrophoresis: effect of Maillard reaction.
AB  - Differences in the acidic silver staining, after sodium dodecylsulphate
      polyacrylamide gel electrophoresis, between the alpha 1 and alpha 2 collagen
      chains, as well as between rat-tail tendon and calf-skin collagen type I, were
      observed. The staining conditions at which the staining differences are both most
      expressed and reproducible were characterized. Age differences between staining
      of the alpha 1 CB6 fragment from young rats (2 and 12 months) and old rats (29
      months) indicated that different susceptibilities of collagen species to the
      silver staining can be the result of different extents of some age-dependent post
      translational modification, such as glycation. In vitro incubation of acid
      soluble rat-tail tendon collagen with various sugars led to an increase in silver
      staining compared with samples incubated in the absence of sugar. This effect was
      inhibited by sodium cyanoborohydride, diethylenetriamine pentaacetic acid and
      aminoguanidine, i.e. compounds inhibiting the Maillard reaction at various
      stages. It can be concluded that the enhanced silver susceptibility of glycated
      collagen is related to advanced-phase Maillard reaction products attached to
      collagen.

PMID- 1400787
TI  - High-performance liquid chromatographic determination of sulphobromophthalein and
      its conjugates.
AB  - A simple, sensitive and selective high-performance liquid chromatographic method
      for the determination of sulphobromophthalein and its mercaptide conjugates in
      rat bile was developed. These pigments, which have an absorption maximum at 580
      nm in alkaline solution, were separated isocratically on an alkali-resistant ODS
      column by paired-ion chromatography. Analysis of bile samples obtained after
      intravenous administration of sulphobromophthalein to rats showed the presence of
      at least twenty peaks of metabolites, of which thirteen were identified and seven
      quantified.

PMID- 1400788
TI  - Determination of cefcanel in plasma and urine by high-performance liquid
      chromatography using coupled columns, after administration of the new
      cephalosporin prodrug cefcanel daloxate hydrochloride.
AB  - A rapid and sensitive high-performance liquid chromatographic method has been
      developed for the determination in plasma and urine of the new cephalosporin
      cefcanel. The method involves a simple deproteinizing step followed by separation
      on a coupled-column chromatographic system with ultraviolet detection. Limits of
      quantification were 0.2 microM for plasma samples and 2 microM for urine samples.
      The method has been used for the determination of cefcanel in various clinical
      studies.

PMID- 1400789
TI  - Automated-extraction, high-performance liquid chromatographic method and
      pharmacokinetics in rats of a highly A2-selective adenosine agonist, CGS 21680.
AB  - CGS 21680 (2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-
      ethylcarboxamidoadenosine, I) is a highly A2-selective (A2/A1 = 140), high
      affinity adenosine agonist. A method has been devised to extract the compound
      from biological matrices with automated solid-phase extraction using C18 bonded
      silica columns. This is followed by reversed-phase, paired-ion chromatography on
      a Supelco LC-18-S column with fluorescence detection. The limit of quantitation
      is 5 ng/ml, but 1 ng/ml (five times the signal-to-noise ratio) can readily be
      detected. Tritium-labeled compound was used to study the pharmacokinetics in
      rats. After an intravenous dose of 0.3 mg/kg, biphasic elimination kinetics were
      observed for parent I, characterized by half-lives of 1.8 min (distribution) and
      15 min (elimination). The volume of distribution in the terminal phase (V beta)
      was low (0.27 l/kg) and plasma clearance was moderate (0.83 l/kg/h). Although the
      compound was rapidly absorbed (mean Tmax = 13 min), low concentrations (mean Cmax
      = 94 ng/ml) were observed after an oral dose of 3.0 mg/kg, and bioavailability
      was only approximately 1.4%. Radioactivity persisted in plasma longer than parent
      compound after either dose, but levels were too low for isolation and structure
      identification of drug-derived compounds.

PMID- 1400790
TI  - Determination of 2-naphthylamine in urine by a novel reversed-phase high
      performance liquid chromatography method.
AB  - A high-performance liquid chromatographic method for the determination of 2
      naphthylamine in urine using fluorescence detection was developed. The method
      validation analysis showed the method to be in analytical control, i.e. the
      distribution of the difference between the observed and true values of the method
      evaluation samples did not deviate significantly from the normal distribution.
      The recovery of the method was 85%. The entire run time of chromatography was 10
      min using isocratic elution (acetonitrile-water, 35:65), and the retention time
      for 2-naphthylamine was 5.8 min. The relative short time of analysis in
      combination with the low limit of detection (0.272 nmol/l) makes the method
      potentially applicable for surveillance of occupational and environmental
      exposure to 2-nitronaphthalene. The developed method is presently used for
      measurement of 2-naphthylamine in urine samples from workers employed at
      factories, characterized by a low airborne exposure level of polycyclic aromatic
      hydrocarbons, i.e. in general less than 25 micrograms/m3. The urine samples of
      exposed workers (n = 95) showed a 2-naphthylamine range of up to 9.4 nmol/l,
      whereas unexposed control individuals (n = 114) showed a range of up to 0.87
      nmol/l.

PMID- 1400791
TI  - Trace quantitation of 4-hydroxy-2-nonenal in biological samples as its oxime-bis
      tert.-butyldimethylsilyl derivative using 3-hydroxynonanal as an internal
      standard.
AB  - A gas chromatographic-mass spectrometric method for the determination of the
      lipid aldehyde 4-hydroxy-2-nonenal (4HNE) in trace quantities is described. The
      method utilizes the reaction of aldehydes with hydroxylamine leading to the
      formation of the oxime derivative. The aldehydes are recovered by octadecylsilyl
      solid-phase extraction and converted to the bis-tert.-butyldimethylsilyl
      derivatives for analysis using electron ionization. A novel 4HNE analogue, 3
      hydroxynonanal, has been synthesized and is used as an internal standard. A limit
      of detection of approximately 1 pmol of 4 HNE in preparations of approximately
      2.10(6) cells or 0.5 ml of whole blood, plasma or serum was observed. Standard
      addition analysis indicates that the method is accurate at these levels.
      Replicate analysis of the National Institutes of Standards and Technology
      Standard Reference Material SRM 909 indicates an average in-run precision of 8.1%
      and a between-run precision of 13.5% at an average concentration of 82.1 pmol/ml
      of reconstituted material.

PMID- 1400792
TI  - Pharmacokinetic and metabolism studies on girisopam by chromatographic and
      spectrometric methods in humans.
AB  - Girisopam possesses selective anxiolytic action without muscle relaxant and
      anticonvulsive activity. After a 100-mg oral dose of 14C-labelled girisopam to
      seven male subjects, the mean recovery of 14C radioactivity was 51% in urine and
      33% in faeces. A high-performance liquid chromatographic method has been
      developed for studying girisopam in single-dose pharmacokinetic studies. The
      serum extract was chromatographed on a normal-phase column using a mobile phase
      of hexane-ethanol-diethyl ether (66:9:25, v/v) and ultraviolet detection at 235
      nm. The recovery was 60% and the detection limit was 3 ng/ml, using 1 ml of
      serum. After a 20-min delay, girisopam is rapidly absorbed. After reaching a mean
      serum level of 178 ng/ml at a mean time of 2.0 h, the serum concentration of
      girisopam decreased with a mean elimination half-time of 22.2 h. The metabolites
      were separated by high-performance liquid chromatography, radio thin-layer
      chromatography and gas chromatography. Their structures were determined by liquid
      chromatography-mass spectrometry, mass spectrometry and gas chromatography-mass
      spectrometry. Their chemical structures were confirmed by comparison with
      synthesized reference compounds. The major urinary metabolites were 7
      demethylgirisopam (I), 4'-hydroxygirisopam (II) and 4-hydroxymethyl-4
      demethylgirisopam (III), which were in conjugated form, and 4-carboxy-4
      demethylgirisopam (V), a compound with an open-chain structure (VII) and traces
      of 4-demethyl-4-oxogirisopam (VIII) and 4-hydroxymethyl-4-demethylgirisopam
      (III), which were in non-conjugated form. The metabolic profile in the serum
      consisted predominantly of the glucuronides of I, II and III. The non-conjugated
      metabolites were the metabolite with the open-chain structure (VII), III and V.
      Besides the parent compound, the faeces sample contained conjugates of I and II.

PMID- 1400793
TI  - In vivo sampling using loop microdialysis probes coupled to a liquid
      chromatograph.
AB  - Microdialysis probes with longer membranes (20-100 mm) provide increased relative
      recovery over traditional shorter probes (1-4 mm) developed for neuroscience
      applications. The characterization and optimization of "straight through" or
      "loop type" probes for use in subcutaneous tissue are considered. Membrane area,
      probe size, inlet and outlet tubing dimensions, and flow-rate are examined for
      their effects on relative recovery, the total collection rate, and bulk flow
      through the membrane wall. Polyacrylonitrile and regenerated cellulose membrane
      fibers with different geometries were compared. Sampling probes used fibers 3-10
      cm long. Inlet and outlet tubing was varied from 25 to 110 microns I.D. with
      lengths of 10 to 50 cm. Probe configurations optimized for relative recovery,
      flow-rate, and utility for in vivo use are presented. Utilizing microdialysis
      probes with large membrane surface areas results in relative concentration
      recovery of greater than 50% at flow-rates of greater than 5 microliters/min.
      Therapeutic drug monitoring in subcutaneous tissue of awake animals is explored.

PMID- 1400794
TI  - Determination of urinary normetanephrine, metanephrine and 3-methoxytyramine by
      high-performance liquid chromatography with electrochemical detection: comparison
      between automated column-switching and manual dual-column sample purification
      methods.
AB  - This report describes a high-performance liquid chromatographic method with
      electrochemical detection for the simultaneous quantitation of urinary
      metanephrine, normetanephrine and 3-methoxytyramine. This method, which involves
      manual dual-column purification steps for the routine determination of urinary
      metanephrines, is compared with the previously used spectrophotometric Pisano
      method and an on-line sample preparation procedure, where the automated
      sequential trace enrichment (ASTED) apparatus is used for the column-switching
      procedure. In order to automate the metanephrine assay, the enrichment technique
      was evaluated against the reference chromatographic method. Bio-Rad urine
      controls gave coefficients of variation of less than 9% at all levels for the
      reference method. Values of less than 19% were found in the reference range with
      the enrichment method, and the recovery of 3-methoxytyramine was also too poor to
      be measured in normal concentrations. The linearity of both methods is sufficient
      to determine pathological levels of these biogenic amines. Future developments
      should be focused on decreasing the variation of between-day assays in an on
      line, automated procedure.

PMID- 1400795
TI  - Application of an organic solvent extraction to the determination of catechol-O
      methyltransferase activity by high-performance liquid chromatography in human
      mononuclear cells.
AB  - We report here a method for measuring mononuclear cell catechol-O
      methyltransferase (COMT) activity which is ideally adapted to clinical studies.
      The method measures the O-methylation of dopamine to 3-methoxytyramine and 4
      methoxy-3-hydroxyphenethylamine. Whole mononuclear cell sonicate is incubated
      with saturating concentrations of dopamine, S-adenosyl-L-methionine and magnesium
      chloride in sodium-potassium phosphate buffer at pH 7.3. An organic solvent
      extraction using ethyl acetate is then used for product separation, followed by
      high-performance liquid chromatography with electrochemical detection for product
      separation and quantification. This method allows both O-methylated products, 3
      methoxytyramine and 4-methoxy-3-hydroxyphenethylamine, to be isolated and
      quantified separately. The apparent Michaelis constants for dopamine and S
      adenosyl-L-methionine using this method are similar to values reported previously
      (0.51 and 14 microM, respectively). The optimal concentration of magnesium
      chloride is eight to ten times higher than previously reported. No endogenous
      inhibitors were apparent using this assay. The within-day coefficient of
      variation using this method is 7% when measuring 3-methoxytyramine and 5% when
      measuring 4-methoxy-3-hydroxyphenethylamine. The between-day coefficient of
      variation is 11%. Mononuclear cell COMT activity can be detected using protein
      concentrations as low as 0.75 mg/ml, corresponding to 2-3 ml of whole blood. The
      small amount of blood required per sample allows multiple sample analysis from a
      single patient, including infants.

PMID- 1400796
TI  - Determination of 2-isopropoxyphenol in urine by capillary gas chromatography and
      mass-selective detection.
AB  - An analytical method for the assessment of the exposure of workers to the
      pesticide propoxur through biological monitoring has been developed. This study
      was part of a survey of occupational exposure to pesticides used in greenhouses
      for the growing of ornamental plants. In order to assess the actual absorbed
      amount of propoxur in the body, an analytical method for its metabolite 2
      isopropoxyphenol in urine was required. This led to the development of a gas
      chromatographic-mass spectrometric assay involving hydrolysis and solvent
      extraction. A mass-selective detector, operated in single-ion mode, provides a
      selective and sensitive quantification of 2-isopropoxyphenol with a detection
      limit of 6 micrograms/l. The method has been validated with respect to the
      hydrolysis of urine samples, analytical recovery of 2-isopropoxyphenol, stability
      of its conjugates, limit of detection, background and precision. The analytical
      recovery from spiked urine was over 95%. 2-Isopropoxyphenol was excreted in urine
      as a conjugate and was stable for at least seven months when stored at -20
      degrees C. It was not detected in urine from non-exposed persons. Between-day
      coefficients of variation were 20, 10, 7 and 4% for concentrations of 15, 29, 150
      and 213 micrograms/l, respectively. Measured as 2-isopropoxyphenol, ca. 80% of an
      orally administered dose of propoxur was excreted in urine within 10 h.

PMID- 1400797
TI  - Trace analysis of quinapril and its active metabolite, quinaprilat, in human
      plasma and urine by gas chromatography-negative-ion chemical ionization mass
      spectrometry.
AB  - A highly specific and sensitive method for the simultaneous determination of
      quinapril and its active metabolite, quinaprilat, in human plasma and urine by
      gas chromatography-negative-ion chemical ionization mass spectrometry is
      described. Quinapril and quinaprilat were extracted from human plasma and urine
      by using a Bond-Elut C18 cartridge. The plasma or urine extract was treated with
      pentafluorobenzyl bromide followed by trifluoroacetic anhydride to convert
      quinapril and quinaprilat into their pentafluorobenzyl-trifluoroacetyl
      derivatives, which were analysed by a selected-ion monitoring method using
      deuterium-labelled internal standards. The limits of quantitation for both
      quinapril and quinaprilat were 0.05 ng/ml in plasma and 0.5 ng/ml in urine. The
      proposed method is applicable to pharmacokinetic and clinical pharmacological
      studies with satisfactory reliability.

PMID- 1400798
TI  - Determination of dioxopiperazine metabolites of quinapril in biological fluids by
      gas chromatography-mass spectrometry.
AB  - The dioxopiperazine metabolites of quinapril in plasma and urine were extracted
      with hexane-dichloroethane (1:1) under acidic conditions. Following
      derivatization with pentafluorobenzyl bromide and purification of the desired
      reaction products using a column packed with silica gel, the metabolites were
      analysed separately by capillary column gas chromatography-electron-impact mass
      spectrometry with selected-ion monitoring. The limits of quantitation for the
      metabolites were 0.2 ng/ml in plasma and 1 ng/ml in urine. The limits of
      detection were 0.1 ng/ml in plasma and 0.5 ng/ml in urine, at a single-to-noise
      ratio of greater than 3 and greater than 5, respectively. The proposed method is
      applicable to pharmacokinetic studies.

PMID- 1400799
TI  - Measurement of azacyclonol in urine and serum of humans following terfenadine
      (Seldane) administration using gas chromatography-mass spectrometry.
AB  - A gas chromatographic-mass spectrometric (GC-MS) method is presented for the
      analysis of azacyclonol (AZA), a metabolite of terfenadine in serum and urine
      specimens. Following an alkaline extraction, AZA and an internal standard were
      derivatized using heptafluorobutyric anhydride. Fourier transform infrared
      spectrometry suggested that two sites on the AZA molecule were derivatized. GC-MS
      of the extracts had a limit of quantitation (LOQ) of 1 ng/ml and linear range of
      1-1000 ng/ml in urine. Four volunteers were administered a therapeutic regimen of
      terfenadine followed by urine and serum specimen collection(s) during the next
      seven days. The results indicated that following a 60-mg dose of terfenadine each
      12 h for five days, (1) AZA appears in urine within 2 h, (2) urine AZA
      concentrations were above the LOQ 72 h following the last dose, (3) peak urine
      concentrations were as high as 19,000 ng/ml, and (4) mean serum concentration
      following the ninth dose was 59 ng/ml.

PMID- 1400800
TI  - Biotransformation of diethenylbenzenes. IV. A simple high-performance liquid
      chromatographic method for separation of urinary metabolites of 1,3
      diethenylbenzene on analytical and semi-preparative scales.
AB  - A simple ion-suppression separation on reversed-phase columns, which is
      applicable for both analytical and semi-preparative work, is described. Six
      urinary metabolites of 1,3-diethenylbenzene (I), namely 1-(3-ethenylphenyl)-1,2
      dihydroxyethane beta-D-glucosiduronates (two isomers, II and III), N-acetyl-S-[1
      (3-ethenylphenyl)-2-hydroxyethyl]cysteine (IV), N-acetyl-S-[2-(3-ethenylphenyl)-2
      hydroxyethyl]cysteine (V), 3-ethenylphenylmandelic acid (VI) and 3
      ethenylphenylglyoxylic acid (VII), were isolated (Fig. 1). Four of them, IV-VII,
      have been identified in our previous work; the two glucosiduronates were
      identified for the first time by 1H NMR spectroscopy, fast atom bombardment mass
      spectrometry, and enzymic hydrolysis yielding 1-(3-ethenylphenyl)-1,2
      dihydroxyethane as an aglycone. The method was reproducible the concentration
      range 0.05-5 mg/ml, the coefficient of variation being less than 7% (n = 5).
      Excretion of II-VI within 24 h in the urine of rats dosed with a single
      intraperitoneal injection of 100, 300 and 600 mg/kg I was determined
      quantitatively. The utility of the method is discussed in comparison with gas
      chromatographic-mass spectrometric techniques used previously.

PMID- 1400801
TI  - Determination of vinca alkaloids in mouse tissues by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic method is described for the
      determination of vinblastine in various normal mouse tissues, such as lung,
      heart, liver, kidney and muscles, and in implanted MO4 tumours. Vincristine was
      used as the internal standard. Freshly obtained mouse tissue or tumour tissue was
      frozen at -20 degrees C and then lyophilized. After lyophilisation, the dry
      tissues were pulverized and homogeneously mixed, and an aliquot was suspended in
      0.1 M hydrochloric acid. The drugs of interest were then isolated from this
      suspension using ion-pair extraction at pH 3 with octylsulphate as counter-ion.
      The obtained extracts were analysed on a reversed-phase system with a cyanopropyl
      stationary phase. The detection limit was 1 ng/l in plasma and 10 ng/g in tissue.
      The extraction recoveries of vincristine and vinblastine were between 45 and 67%,
      and there were no interferences from blank components. Preliminary
      pharmacokinetic data for different mouse tissues and tumour implanted in muscle
      tissue are presented.

PMID- 1400802
TI  - Simultaneous determination of phenolphthalein and phenolphthalein glucuronide
      from dog serum, urine and bile by high-performance liquid chromatography.
AB  - A procedure is described to simultaneously quantitate phenolphthalein and its
      glucuronide metabolite from dog serum, urine and bile using high-performance
      liquid chromatography. The major advantages of this over pre-existing methods
      include direct analysis of the parent compound and glucuronide metabolite without
      enzymatic hydrolysis, increased sensitivity and the potential for automation of a
      large number of samples. Analytes were extracted from serum and urine using a
      combination of liquid- and solid-phase extraction methodology. Bile samples were
      analyzed directly after a twenty-fold dilution with mobile phase. The components
      plus internal standard were separated by reversed-phase high-performance liquid
      chromatography using step gradient elution and quantitated by the absorbance of
      ultraviolet light at 230 nm. Limits of detection from 1 ml of serum, 0.1 ml of
      urine and 0.05 ml of bile were 0.1, 0.5 and 10 microgram/ml for phenolphthalein
      and 0.1, 10 and 50 microgram/ml for phenolphthalein glucuronide, respectively.

PMID- 1400803
TI  - Determination of naproxen and its metabolite O-desmethylnaproxen with their acyl
      glucuronides in human plasma and urine by means of direct gradient high
      performance liquid chromatography.
AB  - Naproxen is metabolized in humans by O-demethylation, and by acyl glucuronidation
      to the 1-O-glucuronide. Naproxen, its metabolite and the conjugates can be
      measured directly by gradient high-performance liquid chromatographic analysis
      without enzymic deglucuronidation. The glucuronide conjugates were isolated by
      preparative chromatography from human urine samples. Mild acidic hydrolysis of
      one urinary conjugate resulted in naproxen. This conjugate was also formed by
      alkaline isomerization of isolated naproxen acyl glucuronide, indicating that the
      structure of this urinary conjugate must have been naproxen isoglucuronide (4-O
      glucuronide). Mild acidic hydrolysis of another urinary conjugate resulted in O
      desmethylnaproxen. This conjugate was also formed by alkaline isomerisation of
      isolated O-desmethylnaproxen acyl glucuronide, indicating that the structure of
      this urinary conjugate must have been O-desmethylnaproxen isoglucuronide (4-O
      glucuronide). Calibriation curves were constructed by enzymic deconjugation of
      samples containing different concentrations of isolated naproxen acyl
      glucuronide, O-desmethylnaproxen acyl glucuronide, and the isoglucuronides of
      naproxen and O-desmethylnaproxen by mild acidic hydrolysis. The limit of
      quantitation of naproxen in plasma is 1.5 microgram/ml. The limits of
      quantitation in urine are: naproxen, O-desmethylnaproxen, naproxen acyl
      glucuronide and O-desmethylnaproxen acyl glucuronide, 1 microgram/ml; the
      isoglucuronide of naproxen and O-desmethylnaproxen, 1.5 microgram/ml. A
      pharmacokinetic profile of naproxen is shown, and some preliminary
      pharmacokinetic parameters of naproxen obtained from two human volunteers are
      given.

PMID- 1400804
TI  - High-performance liquid chromatographic determination of naproxen, ibuprofen and
      diclofenac in plasma and synovial fluid in man.
AB  - High-performance liquid chromatographic assay procedures have been developed for
      naproxen, ibuprofen and diclofenac in human plasma and synovial fluid samples. A
      single liquid-liquid extraction procedure was used to isolate each compound from
      acidified biological matrix prior to the quantitative analysis. A Spherisorb ODS
      column (12.5 cm x 4.6 mm I.D.) was used for all the chromatography. Naproxen was
      eluted with a mobile phase of methanol-Sorensen's buffer at pH 7 (37:63, v/v).
      Ibuprofen and diclofenac were eluted using mobile phases of methanol-water at pH
      3.3 (65:35, v/v and 63:37, v/v, respectively). Diphenylacetic acid was used as
      the internal standard for the assay of naproxen and flurbiprofen was used in the
      analysis of ibuprofen and diclofenac. Inter- and intra-day coefficients of
      variation were less than 7%. The assays were used in clinical studies of the
      three drugs in osteo- and rheumatoid arthritis patients.

PMID- 1400805
TI  - High-performance liquid chromatographic method for the determination of
      alprazolam in plasma using the column-switching technique.
AB  - A reversed-phase high-performance liquid chromatographic method is described for
      the quantitative determination of alprazolam in the plasma of geriatric patients
      in the presence of 4-hydroxyalprazolam, alpha-hydroxyalprazolam, bromazepam,
      oxazepam, lorazepam, clobazam, desmethylclobazam, diazepam and desmethyldiazepam.
      The procedure is based on the enrichment of alprazolam on a PRP-1 pre-column,
      followed by the transfer of the compound in a forflush mode to the analytical
      column. Alprazolam can be quantified reliably down to a minimum concentration of
      1 ng/ml of plasma.

PMID- 1400806
TI  - High-performance liquid chromatographic determination of the stereoselective
      biotransformation of the chiral drug praziquantel.
AB  - A selective reversed-phase high-performance liquid chromatographic method for the
      simultaneous quantification of praziquantel and its monohydroxylated metabolites
      in serum is described. The quantitative analysis was followed by determination of
      the enantiomeric ratio of praziquantel and trans-4-hydroxypraziquantel, the main
      metabolite of praziquantel in humans, on a cellulose tris-3,5-dimethyl
      phenylcarbamate column (Chiralcel OD). Serum level data for five volunteers after
      oral administration of racemic praziquantel were compared with in vitro
      metabolism data for praziquantel, obtained with liver microsomes of different
      species.

PMID- 1400807
TI  - Column switching and high-performance liquid chromatography in the analysis of
      amitriptyline, nortriptyline and hydroxylated metabolites in human plasma or
      serum.
AB  - A column-switching system for the direct injection of plasma or serum samples,
      followed by isocratic high-performance liquid chromatography and ultraviolet
      detection, is described for the simultaneous quantitation of the tricyclic
      antidepressant amitriptyline, its demethylated metabolite nortriptyline and the E
      and Z-isomers of 10-hydroxyamitriptyline and 10-hydroxynortriptyline. The method
      included adsorption of amitriptyline and metabolites on a reversed-phase C8 clean
      up column (10 microns; 20 mm x 4.6 mm I.D.), washing of unwanted material to
      waste and, after on-line column-switching, separation on a cyanopropyl analytical
      column (5 microns; 250 mm x 4.6 mm I.D.). The compounds of interest were
      separated and eluted using acetonitrile-methanol-0.01 M phosphate buffer (pH 6.8)
      (578:188:235, v/v) within less than 20 min. Various drugs frequently co
      administered with amitriptyline or other antidepressants did not interfere with
      the determinations. In plasma samples spiked with 25-300 ng/ml, the recoveries
      were between 84 and 112% and the inter-assay coefficients of variation were 3
      11%. After a minor modification, as little as 5 ng/ml could be quantitated. There
      were linear correlations (r greater than 0.99) between drug concentrations of 5
      500 ng/ml and the detector signal. The method allows routine measurements of
      amitriptyline, nortriptyline and hydroxylated metabolites in blood plasma or
      serum of patients treated with amitriptyline or nortriptyline, and enables the
      results to be reported within 1 h.

PMID- 1400808
TI  - Determination of N-acetylator phenotype using caffeine as a probe compound: a
      comparison of high-performance liquid chromatography and capillary
      electrophoresis methods.
AB  - A test for determining N-acetylator metabolic phenotype has been developed using
      caffeine as a probe drug. A spot sample of urine is taken, and the unextracted
      urine is then analysed by micellar electrokinetic capillary chromatography.
      Phenotype is determined from the peak-area ratio of urinary 5-acetylamino-6
      formylamino-3-methyluracil to 1-methylxanthine. Phenotype assignments using this
      method were compared with those made using a standard high-performance liquid
      chromatography assay, with good agreement between the two methods. The advantage
      of the capillary electrophoresis analysis is that no sample extraction is
      necessary, resulting in a total analysis time of around 20 min, and removing a
      potential source of error.

PMID- 1400809
TI  - Rapid analysis of human serum albumin by high-performance liquid chromatography.
AB  - High-performance liquid chromatographic analysis of human serum albumin, using a
      column containing quaternized dimethyl-aminomethylstyrene-ethylene glycol
      dimethacrylate, was performed by isocratic elution. This column afforded
      resolution of albumin components, such as human mercaptalbumin and human
      nonmercaptalbumin. The method is an alternative to gradient chromatography, and
      allows rapid determination of the albumin components.

PMID- 1400810
TI  - New extraction procedure and high-performance liquid chromatographic method for
      analyzing polyethylene glycol-400 in urine.
AB  - We describe a new, highly efficient method for extracting polyethylene glycol-400
      from urine and for its analysis by isocratic reversed-phase high-performance
      liquid chromatography. This method is an improvement over previously published
      methods in that it does not require the use of ion-exchange resins and
      lyophilization prior to extraction, nor does it require the separation and
      analysis of the individual polymers of polyethylene glycol. The procedure
      described in this report entails extraction with a salt-solvent combination of
      ammonium sulfate and dichloromethane and analysis by reversed-phase high
      performance liquid chromatography. The lower limit of detection was approximately
      0.25 g/l with a 2-ml urine sample. Analytical recoveries of polyethylene glycol
      400 added to urine at 2.5 and 5.0 g/l averaged 97 and 96%, respectively (n = 10).
      Within- and between-day coefficients of variation were less than 5% at 2.5 and
      5.0 g/l. Studies of various urine samples from patients receiving polyethylene
      glycol-400 revealed no interferences from other urine substances.

PMID- 1400811
TI  - Stereoselective high-performance liquid chromatographic assay with fluorometric
      detection for the isomers of mivacurium in human plasma.
AB  - A high-performance liquid chromatographic assay with fluorometric detection was
      developed for the analysis of the stereoisomers of mivacurium, a new short-acting
      neuromuscular blocker, in plasma. The isomers were isolated from plasma by solid
      phase extraction with C18 and anion-exchange cartridges. The extracts were
      chromatographed on a LiChrosphere 60 RP Select B column (125 mm x 4.6 mm I.D.)
      using a mobile phase of acetonitrile-water (4:6, v/v) containing 0.005 M
      octanesulfonic acid. The fluorescence excitation and emission wavelengths were
      202 and 320 nm, respectively. The accuracy and precision of the assay, expressed
      as the percentage deviation of measured values from true values and the
      percentage coefficient of variation, respectively, were less than or equal to 10%
      at all concentrations except for the percentage coefficient of variation at the
      lower limit of quantitation (5 ng/ml). The assay has been successfully used for
      the analysis of plasma samples from a pharmacokinetic study in human volunteers.

PMID- 1400812
TI  - Determination of 3'-deamino-3'-[2(S)-methoxy-4-morpholinyl]doxorubicin, a new
      morpholinyl anthracycline, in plasma by high-performance liquid chromatography
      with fluorescence detection.
AB  - A sensitive and selective high-performance liquid chromatographic method for the
      determination of 3'-deamino-3'-[2(S)-methoxy-4-morpholinyl]doxorubicin and its
      possible 13-dihydro metabolite in human plasma has been developed. The plasma
      samples were buffered and the drugs and internal standard (doxorubicin) were
      extracted with diethyl ether-n-butanol, back-extracted into 0.3 M phosphoric
      acid, then analysed by reversed-phase liquid chromatography. Quantitation was
      achieved by fluorescence detection of the eluate. The linearity, precision and
      accuracy of the method were evaluated. No interference from blank plasma sample
      was observed. The suitability of the method for in vivo samples was checked by
      analysis of plasma samples drawn from female rats that had received repeated
      intravenous doses of the test compound.

PMID- 1400813
TI  - High-performance liquid chromatographic determination of the calcium channel
      blocker nimodipine in monkey plasma.
AB  - A new high-performance liquid chromatographic (HPLC) assay was developed for the
      determination of nimodipine in monkey plasma. An ethyl acetate extraction
      procedure was employed with a reversed-phase HPLC separation for the analysis.
      Absolute recovery of nimodipine from plasma was over 95% with a lower limit of
      quantitation of 10 ng/ml. This method was applied to a preliminary
      pharmacokinetic study in which 0.25 mg/kg nimodipine was administered
      intravenously to three monkeys. Protein binding and stability of nimodipine in
      monkey plasma were also examined. The pharmacokinetic parameters of nimodipine in
      monkeys were similar to those obtained in humans and indicate that monkeys are an
      appropriate animal model for further pharmacokinetic investigations.

PMID- 1400814
TI  - Determination of luxabendazole in biological fluids by high-performance liquid
      chromatography.
AB  - Luxabendazole, a new benzimidazole, is a highly potent broad-spectrum
      anthelmintic. A high-performance liquid chromatographic method has been developed
      for its determination in serum and urine samples. In order to optimize the clean
      up of samples we compared two procedures: C18 Sep-Pak cartridges and
      ultrafiltration through a cellulose membrane with a 30,000 relative molecular
      mass cut-off. In order to obtain the most suitable mobile phase, we studied the
      influence of pH and acetonitrile content on the capacity factor (k').
      Chromatographic separation and quantification were performed on a reversed-phase
      column packed with 5-microns Nucleosil C18. The mobile phase was acetonitrile
      0.05 M phosphate buffer (pH 7.0), (40:60, v/v). The column effluent was monitored
      by ultraviolet-visible spectrophotometry at 290 nm. The method shows good
      recovery, precision and accuracy. The lower limit of detection for luxabendazole
      is 15 ng/ml in serum samples and 25 ng/ml in urine samples.

PMID- 1400815
TI  - High-performance liquid chromatographic determination of morphine, morphine-3
      glucuronide, morphine-6-glucuronide and codeine in biological samples using multi
      wavelength forward optical detection: a reply.

PMID- 1400818
TI  - High-performance liquid chromatographic separation and detection methods for
      anabolic compounds.
AB  - The role of high-performance liquid chromatography (HPLC) in methods of analysis
      for anabolic compounds in biological samples is reviewed. Special attention is
      given to both the separation and detection of anabolic compounds. A distinction
      is made between on-line detection systems, such as ultraviolet detection and
      diode-array detection, and off-line detection methods with special emphasis on
      immunochemical detection methods using non-isotopic labels. A number of
      applications are given to elucidate the possibilities of HPLC in the analysis of
      anabolic compounds.

PMID- 1400819
TI  - Drug detection in hair by chromatographic procedures.
AB  - This article reviews the analysis of 31 drugs and drug metabolites in human hair
      by thin-layer chromatography, high-performance liquid chromatography, gas
      chromatography, gas chromatography-mass spectrometry and mass spectrometry. The
      most important detection method after chromatographic separation of the
      components is the mass spectrometry because of its sensitivity and specificity.
      Washing steps to exclude external contamination, extraction, derivatization,
      stationary phases, detection modes and detection limits of the mass spectrometric
      and gas chromatographic-mass spectrometric procedures are presented in five
      tables. Additionally, a method for a gas chromatographic-mass spectrometric
      screening procedure is presented.

PMID- 1400820
TI  - Chromatographic methods for the determination of toxicants in faeces.
AB  - Modern chromatographic techniques and their application in the determination of
      toxic compounds in faeces are reviewed. Faecal analysis may be of importance in
      toxicokinetic studies of xenobiotics in order to determine factors such as
      metabolism, body burden and major routes of elimination. Compounds of interest
      include various food constituents, drugs and occupational or environmental
      factors. Further, various mutagenic or carcinogenic compounds which are excreted
      by faeces have been indicated to represent risk factors for colorectal cancer. In
      this context, the chromatographic determination of the endogenously generated
      fecapentaenes and bile acids, both postulated etiological factors in colorectal
      carcinogenesis, is reviewed. For fecapentaene determination, several high
      performance liquid chromatographic (HPLC) methods are available; however, the
      applicability of some of these methods is limited owing to insufficient
      separation of various isomeric forms or discrimination between fecapentaenes and
      their precursors. For the determination of bile acids in faeces, many
      chromatographic procedures have been reported, and the characteristics of the
      most relevant methods are compared and discussed. It is concluded that separation
      by gas chromatography (GC) in combination with mass spectrometry provides the
      highest selectivity and sensitivity. A relatively rapid alternative analysis for
      the determination of total and aqueous faecal bile acids is proposed. Further,
      methods for the determination of polycyclic aromatic hydrocarbons (PAHs) are
      reviewed. Although the use of radiolabelled PAHs in animal studies has many
      advantages, it cannot be applied for human biological monitoring and HPLC and GC
      provide sensitive alternatives. An HPLC method for the determination of non
      metabolized PAHs in faeces is described.

PMID- 1400821
TI  - Chromatographic methods for blood alcohol determination.
AB  - This review is focused on the different chromatographic strategies for blood
      alcohol determination which can be adopted for clinical and/or forensic purposes.
      Particular attention is paid to gas chromatography and to high-performance liquid
      chromatography. However, other analytical techniques in common use, such as
      chemical and enzymic methods, are also briefly presented, together with some, at
      present unusual or experimental, approaches, such as enzymic reactors and
      catalytic electrodes, which are suitable for application in column liquid
      chromatography. Finally, mention is made of the methods for the determination of
      acetaldehyde, the major ethanol metabolite, and of some proposed markers of
      chronic alcohol abuse, such as acetaldehyde-protein adducts and carbohydrate
      deficient transferrin. In order to give the background of knowledge for the
      rational choice of an analytical strategy, an updated outline of ethanol
      metabolism and toxicology is presented, together with basic information for the
      interpretation of the results. Problems concerning blood sampling and storage are
      also discussed.

PMID- 1400822
TI  - Chromatographic separation of marine organic pollutants.
AB  - A review and discussion of the chromatographic separation of marine organic
      pollutants is given, including sampling and clean-up procedures, fractionation
      and enrichment of marine pollutants, capillary gas chromatography (cGC) and high
      performance liquid chromatography applying both classical and chiral stationary
      phases. The potential of multi-dimensional cGC for the analysis of marine organic
      trace pollutants is discussed for polychlorinated biphenyls (PCBs). The
      chromatographic separation of coplanar PCBs and of the enantiomers of chiral
      pollutants provides a further insight into the toxic potential of these marine
      organic pollutants.

PMID- 1400823
TI  - Strategies for the identification of non-polar toxicants in aqueous environmental
      samples using toxicity-based fractionation and gas chromatography-mass
      spectrometry.
AB  - Toxicity-based fractionation is a useful tool for the isolation and
      identification of non-polar organic compounds that are present at toxic
      concentrations in aqueous environmental samples. Methods for isolating such
      toxicants from the aqueous sample matrix and techniques for fractionating the
      compounds for the purpose of reducing the complexity of the sample matrix and
      thus facilitating identification are evaluated. Strategies for analyzing gas
      chromatographic-mass spectrometric data and confirming toxicant identification
      are presented. Studies that use toxicity-based fractionation for identifying the
      cause of toxicity in aqueous environmental samples such as municipal and
      industrial wastewater treatment plant effluents and ambient waters are discussed.

PMID- 1400824
TI  - Determination of aromatic hydrocarbons and their metabolites in human blood and
      urine.
AB  - Methods for the biological monitoring of aromatic hydrocarbons and their
      metabolites in the human blood and urine are reviewed. For the determination of
      the unchanged aromatic hydrocarbon in blood, gas chromatographic head-space
      analysis is recommended. The metabolites can be monitored by photometric, thin
      layer chromatographic, high-performance liquid chromatographic and gas
      chromatographic methods. For the assessment of health risks caused by aromatic
      hydrocarbons, reference values and occupational limit values, expressed as
      biological tolerance values and biological exposure indices, have to be
      considered.

PMID- 1400825
TI  - Methods for the analysis of persistent chlorinated hydrocarbons in tissues.
AB  - Chlorinated hydrocarbons bioaccumulate in tissues and may have severe health
      consequences. These compounds occur individually, in small groups or as complex
      mixtures; examples of each category include aldrin, hexachlorocyclohexane and the
      polychlorinated biphenyls. Tissue extraction and purification schemes have been
      established, although new approaches such as supercritical fluid extraction are
      promising. Analyses often require the resolving power of capillary gas
      chromatography, in combination with the sensitivity and selectivity of electron
      capture detection, electrolytic conductivity detection and mass spectrometry.
      Difficulties arise in quantitating chlorinated hydrocarbons in tissues, due to
      the number of components present and the fact that individual constituents may be
      reduced or enhanced in concentration in tissues, compared with the original
      formulation. Congener specific analysis and computer-assisted identification
      techniques have been applied to the problem.

PMID- 1400826
TI  - Methods for chromatographic determination of amanitins and related toxins in
      biological samples.
AB  - Methods for the chromatographic determination of amanitins, toxins of Amanita
      phalloides (Fr.), Link mushrooms and related toxins are reviewed; particular
      emphasis is given to high-performance liquid chromatographic methods. The main
      chemical and toxicological aspects are discussed, but the focus of the present
      review is on the analytical problems arising in a laboratory charged with the
      setting up of a procedure which can direct the appropriate clinical management of
      an intoxicated patient or solve a forensic case.

PMID- 1400827
TI  - 32P-postlabelling and mass spectrometric methods for analysis of bulky,
      polyaromatic carcinogen-DNA adducts in humans.
AB  - There has been significant recent progress toward the development of human
      carcinogen-DNA adduct biomonitoring methods. 32P-Postlabelling is a technique
      which has found wide application in human studies. 32P-Postlabelling involves
      enzymatic preparation and labelling of DNA samples, followed by chromatographic
      separation of carcinogen-nucleotide adducts from unadducted nucleotides. Thin
      layer ion-exchange and high-performance liquid chromatography (HPLC) have been
      utilized. This paper critically reviews 32P-postlabelling methods for analysis of
      bulky, polyaromatic carcinogen-DNA adducts and details a strategy to optimize
      this technique for monitoring human samples. Development of a human carcinogen
      biomonitoring method requires that the biomarker meet certain criteria: that the
      biomarker be responsive to exposures known to increase human cancer risk, to
      reductions in those exposures, and to the influence of metabolic differences. In
      addition, reliable samples must be available by non-invasive means. The ability
      of 32P-postlabelling to meet these criteria is traced in the literature and
      discussed. Identification of specific carcinogen-DNA adducts is a difficult task
      due to the low (femtomole) levels in human target tissues. Because co
      chromatography in thin-layer chromatography (TLC) is generally not considered to
      be proof of chemical identity, both synchronous fluorescence and HPLC in
      conjunction with 32P-postlabelling and TLC are used to confirm the identity of
      specific carcinogen-DNA adducts in human samples. Mass spectrometry is a highly
      specific method, the sensitivity of which has been improved to the point which
      may allow its use to confirm the identity of carcinogen-DNA adducts isolated by
      32P-postlabelling and other methods. The literature relating to the use of mass
      spectral techniques in carcinogen-DNA adduct analysis is reviewed.

PMID- 1400828
TI  - Systematic toxicological analysis of drugs and their metabolites by gas
      chromatography-mass spectrometry.
AB  - Gas chromatographic-mass spectrometric (GC-MS) procedures for the systematic
      toxicological analysis of several categories of drugs relevant to clinical
      toxicology, forensic toxicology and doping control are reviewed. Papers from 1981
      to 1991 are taken into consideration. They describe the detection of acute or
      chronic intoxication and the detection of drug abuse. Screening procedures are
      included for the following categories: barbiturates and other sedative-hypnotics,
      anticonvulsants, benzodiazepines, antidepressants, phenothiazine and
      butyrophenone neuroleptics, central stimulants (amphetamines, cocaine),
      hallucinogens (LSD, phencyclidine, tetrahydrocannabinol), opioid (narcotic) and
      other potent analgesics, non-opioid analgesics, antihistamines (histamine H1
      receptor blockers), antiparkinsonian drugs, beta-blockers (beta-adrenoceptor
      blockers), antiarrhythmics (class I and IV), diuretics, laxatives and their
      metabolites. Methods for confirmation of results obtained by screening procedures
      using immunoassay or chromatographic techniques are also included. GC-MS
      procedures for the simultaneous detection of several categories of drugs, the so
      called "general unknown analysis", are reviewed. The toxicological question to be
      answered and the consequence for the choice of an adequate method, the sample
      preparation and the chromatography itself are discussed. The basic information
      about the biosample assayed, work-up, GC column, mass spectral detection mode,
      reference data and sensitivity of each procedure are summarized in tables,
      arranged according to the category of drug. Examples of typical GC-MS
      applications are presented. Fragment ions that are suitable for mass spectral
      screening for particular categories of drugs and for general unknown are
      tabulated.

PMID- 1400829
TI  - Detection of the enzymatic activity of cytochrome P-450 enzymes by high
      performance liquid chromatography.
AB  - The reactions catalysed by the various cytochrome P-450 enzymes are reviewed with
      respect to the analysis of products by high-performance liquid chromatography
      (HPLC). Especially biotransformation reactions of purified cytochrome P-450
      enzymes in a reconstituted system and in microsomes mainly of rat liver origin
      are considered. Emphasis is put on the specificity of product formation due to
      the individual isozymes of cytochrome P-450. It is shown that the presence of
      eight cytochrome P-450 isozymes can be monitored and determined by specific
      product formation after HPLC analysis, which is an important parameter in
      toxicological studies.

PMID- 1400830
TI  - Gas chromatographic analysis of nicotine and cotinine in hair.
AB  - Non-invasive validation of cigarette- or cigar-smoking behaviour is necessary for
      large population studies. Urine or saliva samples can be used for confirmation of
      recent nicotine intake by analysis of cotinine, the major metabolite of nicotine.
      However, this test is not suitable for validation of survey data, since the
      quantification of cotinine in saliva only reflects nicotine exposure during the
      preceding week. To validate information on tobacco use, we investigated hair
      samples for quantifying nicotine and cotinine by gas chromatography-mass
      spectrometry. Hair (about 50-100 mg) was incubated in 1 M sodium hydroxide at 100
      degrees C for 10 min. After cooling, samples were extracted by diethyl ether,
      using ketamine as an internal standard. Drugs were separated on a 12-m BP-5
      capillary column, and detected using selected-ion monitoring (m/z 84, 98 and 180
      for nicotine, cotinine and ketamine, respectively). Hair from non-smokers and
      smokers contained nicotine and cotinine. Although it is difficult to determine an
      absolute cut-off concentration, more than 2 ng of nicotine per milligram of hair
      can be used to differentiate smokers from non-smokers. Some applications of this
      technique are developed to determine the status of passive smokers, the
      gestational exposure in babies and the pattern of an individual's nicotine use by
      cutting strands of hair into sections of one-month intervals.

PMID- 1400831
TI  - Electrophoretic analysis of snake venoms.
AB  - Electrophoretic analyses were conducted on snake venoms from 21 species
      representing Elapidae, Crotalidae and Viperidae. Denatured and native venoms were
      analyzed by polyacrylamide gel electrophoretic (PAGE) methods with sodium dodecyl
      sulfate (SDS) and without SDS. Both SDS-PAGE and PAGE profiles of venoms from
      different snake species indicate that some proteins and polypeptide components of
      these venoms have common electrophoretic characteristics suggesting a genetic
      relationship. Conversely, the electropherograms also showed the characteristic
      protein and polypeptide profiles that could differentiate one snake species from
      another. Therefore, both SDS-PAGE and PAGE profiles suggest that proteins and
      polypeptides with similar characteristics abound among subspecies or related
      species, although each venom has a unique profile that differentiates one species
      from the other.

PMID- 1400832
TI  - Rapid assay of cocaine, opiates and metabolites by gas chromatography-mass
      spectrometry.
AB  - The simultaneous assay of cocaine, opiates and metabolites in small biological
      samples continues to be a difficult task. This report focuses upon tabulation of
      important techniques (extraction, derivatization, chromatographic conditions,
      detection mode, data acquisition) reported over the last decade that were used in
      the development of assays for these analytes. The most prevalent procedures for
      extraction of cocaine, opiates and metabolites were liquid-liquid and solid-phase
      extraction isolation methods. Following extraction analytes were derivatized and
      analyzed by gas chromatography-mass spectrometry. The technique most often used
      for chromatographic separation was fused-silica capillary column gas
      chromatography. Detection generally was performed by selected ion monitoring in
      the positive-ion electron-impact ionization mode, although full-scan acquisition
      and positive- and negative-ion chemical ionization methods have been used. It was
      apparent from the review that there is a continuing need for greater sensitivity
      and selectivity in the assay of highly potent opiates and for cocaine and
      metabolites.

PMID- 1400833
TI  - Determination of methamphetamine enantiomer ratios in urine by gas chromatography
      mass spectrometry.
AB  - Analysis of the enantiomers of methamphetamine and its metabolite amphetamine is
      an extremely important process for a number of scientific disciplines. From
      studies of biological activity and mechanisms through determination of precursor
      molecules in a criminal investigation are all served by this analytical
      procedure. Utilization of gas chromatography-mass spectrometry with chiral
      derivatizing reagents is the most common chiral procedure and produces excellent
      results. Of the chiral derivatizing reagents available, the most widely used is
      trifluoroacetyl-l-prolyl chloride (TPC). Utilization of other derivatives require
      either synthesis by the analyst or have not shown themselves to provide as good a
      separation as did the TPC reagent. Use of chiral stationary phases yield good
      results but the disadvantages of temperature limits of these columns and the
      narrow use to which the columns can be put has limited their utilization. A
      significant utility of the chiral stationary phase is the ability to determine
      the purity of a chiral derivatizing reagent. Even if not used for routine
      analysis of enantiomers, utilization of this procedure can determine the purity
      of a reagent such as TPC and allow for accurate calculation of actual amounts of
      each enantiomer. This can be estimated using chiral derivatives on an achiral
      column, but it is limited to the extent that it is not able to differentiate
      enantiomeric impurity in the reagent versus the drug itself. Description of
      chromatographic procedures primarily focusing on gas chromatographic-mass
      spectrometric techniques but also including liquid chromatographic techniques
      along with examples of extraction and derivatization procedures is the focus of
      this review.

PMID- 1400834
TI  - Chromatographic and mass spectrometric methods for determination of lysergic acid
      diethylamide (LSD) and metabolites in body fluids.
AB  - Continued illicit use of the potent psychedelic drug lysergic acid diethylamide
      (LSD) has stimulated efforts to develop effective analytical methods for
      detection of the drug and its metabolites in body fluids from suspected LSD
      users. Recently reported methods based on gas and liquid chromatography, combined
      with single- and multiple-stage mass spectral analysis, now permit accurate
      detection and quantitation of LSD at sub-nanogram/milliliter concentrations.

PMID- 1400835
TI  - Inclusion and fractionated release of nucleic acids using microcapsules made from
      plant cells.
AB  - The encapsulation and fractionated release of nucleic acids on vesicular packing
      (VP) materials have been investigated. The earlier described dependence of the
      permeation of nucleic acid molecules through the vesicle membranes on the salt
      concentration is a necessary precondition for both encapsulation and
      fractionation. Encapsulation is achieved by applying a suitable sample onto a VP
      column that has been equilibrated with a high-salt buffer. In that buffer the
      sample molecules are permeable. Immediately after sample application, elution is
      started with a low-salt buffer, from which the sample molecules are excluded. At
      the front between the two buffers the permeability changes, and some of the
      sample molecules distributed inside the vesicles cannot pass through the
      membranes. These encapsulated molecules can be released by increasing the salt
      concentration in the eluent. If the encapsulated nucleic acid sample is
      polydisperse, a stepwise or linear increase in the salt concentration leads to a
      fractionated release. The fractions obtained differ in their molecular size
      composition.

PMID- 1400836
TI  - High-performance liquid chromatography and post-column derivatization with
      diphenyl-1-pyrenylphosphine for fluorimetric determination of triacylglycerol
      hydroperoxides.
AB  - Triacylglycerol monohydroperoxides (TG-mHPO) were selectively detected at the
      picomole levels after post-column reaction with diphenyl-1-pyrenylphosphine
      (DPPP). TG-mHPO were separated on two types of reserved-phase columns, an ODS
      column and a phenylated silica gel column, which were useful for determining TG
      mHPO at their molecular species levels and their class levels, respectively.
      After the separation, DPPP solution was mixed with the eluent followed by
      reaction in a stainless-steel coil 20 m x 0.5 mm I.D. at 80 degrees C, then the
      fluorescence intensity of DPPP oxide was measured (lambda ex. 352 nm, lambda em.
      380 nm). Using these systems, TG-mHPO were determined in the range 2-1000 pmol.
      The relative standard deviations were 2.3-2.8%.

PMID- 1400837
TI  - Purification of serine hydroxymethyltransferase from Bacillus stearothermophilus
      with ion-exchange high-performance liquid chromatography.
AB  - The gene of serine hydroxymethyltransferase (SHMT) of a thermophilic bacterium
      Bacillus stearothermophilus was expressed in Escherichia coli, and SHMT was
      successfully purified from the crude extract of E. coli in two steps while
      maintaining the enzymatic activity. The purification steps involved ammonium
      sulphate precipitation followed by high-performance liquid chromatographic
      separation using the anion-exchange column Fractogel EMD DEAE-650(S). In addition
      to the DEAE column, three other types of anion- and cation-exchange columns were
      also studied for their ability to separate SHMT, and the performance of the four
      columns were compared.

PMID- 1400838
TI  - Determination of tetracyclines in bovine and porcine muscle by high-performance
      liquid chromatography using solid-phase extraction.
AB  - A method is presented for the determination of the three tetracyclines
      oxytetracycline, tetracycline and chlortetracycline in muscle, spiked at 100
      ng/g, using high-performance liquid chromatography (HPLC). The concentration and
      extraction steps are carried out using Waters Environmental Sep-Pak cartridges.
      The principal steps involve homogenizing the sample in EDTA-McIlvaine buffer
      followed by centrifugation and precipitation of the supernatant using
      trichloroacetic acid. After further filtration and concentration on a Sep-Pak
      cartridge, the sample is eluted and analysed by HPLC with UV detection and
      confirmation by diode-array. The column used is a Nova-Pak C18 (4 microns)
      cartridge (10 cm x 8 mm I.D.). A phosphate-citrate-acetonitrile buffer, utilizing
      ion suppression, is the mobile phase. The analytes are detectable at levels down
      to 10 ng/g. The analyte identity can be confirmed at 20 ng/g by the use of diode
      array detection and spectral library comparison.

PMID- 1400839
TI  - Determination of alendronate in pharmaceutical dosage formulations by ion
      chromatography with conductivity detection.
AB  - A method was developed and validated for the direct determination in
      pharmaceutical dosage formulations of alendronate, a non-chromophoric compound.
      It is based on the use of single-column ion chromatography with conductivity
      detection that obviates the need for the tedious chemical derivatization
      procedures that are required for UV and fluorescence detection. Diluted samples
      of 0.05 mg/ml were chromatographed directly on a Waters IC-Pak HR anion-exchange
      column or a Dionex OmniPac PAX-100 column with dilute nitric acid as the mobile
      phase followed by conductivity detection. The method was validated and shown to
      be precise, accurate and specific for the assay of alendronate in intravenous
      (i.v.) solution and tablet formulations. The ruggedness of the assay was studied
      by generating data from four different instruments. Also established was the
      equivalence between this method and a previously reported high-performance liquid
      chromatographic method with 9-fluorenylmethyl chloroformate derivatization and UV
      detection. Application of the method to the determination of alendronate in i.v.
      and tablet formulations is presented and the performances of the Waters IC-Pak HR
      and Dionex OmniPac columns are discussed.

PMID- 1400840
TI  - Enzymophoresis of nucleic acids by tandem capillary enzyme reactor-capillary zone
      electrophoresis.
AB  - Enzymophoresis with coupled heterogeneous capillary enzyme reactor-capillary zone
      electrophoresis was developed and evaluated in the area of nucleic acids.
      Ribonuclease T1, hexokinase and adenosine deaminase were successfully immobilized
      on the inner walls of short fused-silica capillaries through glutaraldehyde
      attachment. These open-tubular capillary enzyme reactors were quite stable for a
      prolonged period of use under operation conditions normally used in capillary
      zone electrophoresis. The capillary enzyme reactors coupled in series with
      capillary zone electrophoresis served as peak locator on the electropherogram,
      improved the system selectivity, and facilitated the quantitative determination
      of the analytes with good accuracy. Also, they allowed the on-line digestion and
      mapping of minute amounts of transfer ribonucleic acids, and the simultaneous
      synthesis and separation of nanogram quantities of oligonucleotides.

PMID- 1400841
TI  - Determination of limiting ionic mobilities and dissociation constants of some
      local anaesthetics.
AB  - The limiting ionic mobilities and thermodynamic acid dissociation constants were
      calculated from isotachophoretic experiments for the local anaesthetics procaine,
      tetracaine, lidocaine, trimecaine, bupivacaine, cinchocaine, diperodone,
      diocaine, cocaine, psicaine-neu, tropacocaine, amylocaine, beta-eucaine and
      leucinocaine. The pH values at which the local anaesthetics with very similar
      limiting ionic mobilities can be isotachophoretically separated were determined
      from simulated mobility curves. The measuring apparatus employed a high-frequency
      contactless conductivity detector.

PMID- 1400842
TI  - Determination of topanol antioxidants in methacrylates using capillary gas-liquid
      chromatography.
AB  - This paper presents a method to identify and determine topanol A and topanol O
      antioxidants in methylmethacrylate and 11-bromoundecylmethacrylate. The method is
      both simple and rapid. Analysis is performed on a 10 m x 0.53 mm I.D. HP-1
      capillary gas chromatography column with a temperature gradient and a high
      carrier gas flow-rate (16.5 ml/min). Quantitation is by internal standardisation.
      Validation of the method is described for both topanols at concentrations of
      approximately 50 ppm in methylmethacrylate and 250 ppm in 11
      bromoundecylmethacrylate.

PMID- 1400843
TI  - Support matrix effects in the reversed-phase thin-layer chromatography of some
      peptides.
AB  - The retentions of 28 peptides in reversed-phase thin-layer chromatography (RPTLC)
      were determined on cellulose and on impregnated cellulose and alumina layers with
      1-propanol as the organic component of the mobile phase. Each peptide showed a
      support matrix effect: their RM values first decreased to a minimum, then
      increased with increasing 1-propanol concentration. On cellulose layers only the
      increasing phase was observed. The retention behaviour of peptides was adequately
      described with a quadratic or linear function, but the slope value of the linear
      function had a positive value. The results demonstrate that the support matrix
      effect can be observed on non-silica supports and it may occur in reversed-phase
      chromatography in the case of polar solutes and supports with free adsorptive
      centres on their surfaces. Both the intercept and slope values of the function
      are needed to describe the lipophilicity of peptides, but the correlation is not
      strong enough for the determination of the lipophilicity of peptides by RPTLC.
      Principal component analysis showed that the peptides form distinct clusters on
      the basis of their retention characteristics: peptides containing a basic amino
      acid, peptides with a ring structure in the amino acid side-chain and peptides
      containing uncharged amino acids.

PMID- 1400844
TI  - Contribution of ionically immobilized bovine serum albumin to the retention of
      enantiomers.
AB  - The retention of the enantiomers of mandelic acid and N-benzoylalanine was
      studied on columns prepared by immobilizing bovine serum albumin (BSA) on an
      anion exchanger. The amount of BSA fixed on the column is easy to adjust and
      measure. The adsorption isotherms were determined. For each enantiomer, the
      isotherm is well accounted for by a bi-Langmuir equation. One term of the
      isotherm (which is the same for both enantiomers) corresponds to non-selective
      interactions and the other term to the chiral selective interactions. The column
      saturation capacity of this second term is 8% larger for the less strongly
      retained enantiomer. This saturation capacity corresponds approximately to one
      enantiomer molecule adsorbed for five BSA molecules immobilized. This result is
      in agreement with the assumption of the hydrophobic cavity of BSA being the
      chiral selective site.

PMID- 1400845
TI  - Determination of erythromycin ethylsuccinate by liquid chromatography.
AB  - A method is described for the determination of erythromycin ethylsuccinate by
      liquid chromatography. A C18 reversed-phase column (25 cm x 4.6 mm I.D.) was used
      with acetonitrile-0.2 M tetrabutylammonium sulphate (pH 6.5)-0.2 M phosphate
      buffer (pH 6.5)-water [x:5:5:(90-x)] as mobile phase. The proportion of
      acetonitrile (x) has to be adapted to the type of stationary phase used. For RSil
      C18 LL, 42.5% was used. The column was heated at 35 degrees C, the flow-rate was
      1.5 ml/min and UV detection was performed at 215 nm. The main component,
      erythromycin A ethylsuccinate, was separated from all other components which were
      present in commercial samples. The main impurities were erythromycin A and the
      ethylsuccinate esters of erythromycin B and C. The amide N-ethylsuccinyl-N
      demethylerythromycin A was shown to be present in all the samples examined. The
      method was successfully applied to the analysis of specialities.

PMID- 1400846
TI  - Coupled-column high-performance liquid chromatographic method for the
      determination of 1-hydroxypyrene in urine of subjects exposed to polycyclic
      aromatic hydrocarbons.
AB  - A coupled-column high-performance liquid chromatographic system for integrated,
      on-line sample processing and the determination of free and conjugated 1
      hydroxypyrene in urine has been developed. The method is based on a "tailor-made"
      copper phthalocyanine-modified porous-glass precolumn packing material, which
      allows a direct and repeated injection of urine samples and a selective
      enrichment of trace amounts of particular components. The fully automated method
      has a low detection limit (0.01 pmol), a quantitative and matrix-independent
      recovery and a highly reliability, as shown by an interlaboratory comparison of
      methods.

PMID- 1400847
TI  - Purification of DNA-derived deoxynucleotides from leukocytes involving nuclease
      elution of an ion-exchange column.
AB  - A method has been developed in which the DNA of leukocytes (as the buffy coat
      from blood) is isolated in the form of its constituent deoxynucleotides. The
      steps in this method are as follows: (1) lyse the leukocytes with sodium dodecyl
      sulfate (SDS) and enzymatically digest the proteins and RNA, (2) remove the SDS
      on a non-polar adsorbent (Bio-Beads SM-4) and then trap the DNA on a quaternary
      amine silica cartridge, (3) wash the column with 1 M NaCl-buffer, (4) digest the
      DNA on the column with staphylococcal nuclease and (5) elute the digested DNA
      with 0.5 M NaCl-buffer and digest it further with bovine spleen phosphodiesterase
      II to deoxynucleotide-3'-monophosphates. From a 40-microliters sample of butty
      coat was obtained 126 +/- 14 micrograms (two experiments, eight sample total) of
      deoxynucleotides. Reversed-phase high-performance liquid chromatography, which
      removed the added enzymes, showed only peaks for deoxynucleotides. For
      comparison, the amount of deoxynucleotides obtained from the leukocytes by an
      automated phenol extraction procedure was 101 +/- 5.4 micrograms (one experiment
      in triplicate).

PMID- 1400848
TI  - Purification of recombinant human interferon-beta by immobilized antisense
      peptides.
AB  - Synthetic antisense peptides encoded in the antisense strands of DNA
      corresponding to the 1-14, 42-54 and 103-115 fragments of the human interferon
      beta sequence were applied in the purification of recombinant human interferon
      beta from a mammalian cell culture. The protein fragments were selected on the
      basis of their computer-predicted exposure on the surface of the protein. The
      antisense peptides were synthetized by the solid-phase method directly on the
      resin used as the stationary phase in affinity chromatography. All the tested
      antisense peptides showed a selective affinity for human interferon-beta,
      permitting a ten-fold purification of the protein.

PMID- 1400849
TI  - Supercritical fluid extraction of chemical warfare agent simulants from soil.
AB  - Chemical warfare agent simulants are efficiently recovered from 2-ppm spikes in 1
      g of Rocky Mountain Arsenal Standard Soil using methanol-carbon dioxide (5:95) at
      300 atm for 2 min at 60 degrees C. Recoveries (n = 3) were 79 +/- 23% for
      dimethylmethylphosphonate, 93 +/- 14% for 2-chloroethylethyl sulfide, 92 +/- 13%
      for diisopropylfluorophosphate and 95 +/- 17% for diisopropylmethylphosphonate.
      Recoveries are higher than, but less precise than those achieved from a 5-min
      ultrasonic micro-scale extraction using methanol. Much less laboratory waste is
      generated than the current standard organic solvent extraction method (33 g of
      soil shaken with 100 ml of chloroform).

PMID- 1400851
TI  - Capillary gel electrophoresis of single-stranded DNA fragments with UV detection.
AB  - Capillary gel electrophoresis has proven to be a powerful tool in biomedical
      research. We report our investigation of some of the critical parameters
      affecting separations of single-stranded DNA fragments as monitored by
      ultraviolet (UV) absorbance detection. Although not as sensitive as laser-induced
      fluorescence (LIF), UV absorbance detection allows one to calculate quite
      accurately, and inexpensively, the molarity of each separated DNA fragment and,
      moreover, the signal "fading" effect normally observed with LIF detection can be,
      in many cases, substituted for fluorescence to detect the many different single
      stranded DNAs, as well as for detection of sequencing reactions.

PMID- 1400850
TI  - Capillary zone electrophoresis of linear and branched oligosaccharides.
AB  - The electrophoretic behavior of derivatized linear and branched oligosaccharides
      from various sources was examined in capillary zone electrophoresis with
      polyether-coated fused-silica capillaries. Two UV-absorbing (also fluorescent)
      derivatizing agents (2-aminopyridine and 6-aminoquinoline) were utilized for the
      electrophoresis and sensitive detection of neutral oligosaccharides, e.g., N
      acetylchitooligosaccharides, high-mannose glycans and xyloglucan
      oligosaccharides. The oligosaccharides labelled with 6-aminoquinoline yielded
      eight times higher signal than those tagged with 2-aminopyridine. Plots of
      logarithmic electrophoretic mobilities of labelled N-acetylchitooligosaccharides
      with 6-aminoquinoline or 2-aminopyridine versus the number of sugar residues in
      the homologous series yielded straight lines in the size range studied, the
      slopes of which were independent of the tagging functions. The slopes of these
      lines are referred to as the N-acetylglucosaminyl group mobility decrement. The
      oligosaccharides were better resolved in the presence of tetrabutylammonium
      bromide in the running electrolyte. Furthermore, the electrophoretic mobilities
      of branched oligosaccharides were indexed with respect to linear
      homooligosaccharides, an approach that may prove valuable in correlating and
      predicting the mobilities of complex oligosaccharides.

PMID- 1400852
TI  - Determination of the herbicide diclofop in human urine.
AB  - A simple and sensitive method for the gas chromatographic determination of
      diclofop residues in human urine is described. Recoveries of diclofop, as its
      methyl ester, from fortified urine were greater than 85% at 100, 50, 10 and 1
      micrograms kg-1, and were similar with and without the inclusion of a hydrolytic
      step in the analytical method. However, a hydrolytic step was necessary for
      analysis of 24-h urine samples collected from a male applicator following a
      single exposure to diclofop-methyl during application to wheat using a tractor
      pulled sprayer. Diclofop residues determined with hydrolysis were approximately
      double those without hydrolysis, suggesting that a significant portion of
      diclofop was excreted in the conjugated form.

PMID- 1400853
TI  - Liquid chromatography and postcolumn indirect detection of glyphosate.
AB  - Glyphosate [N-(phosphonomethyl)glycine] and its metabolite aminomethylphosphonic
      acid (AMPA) were separated and detected by a postcolumn indirect detection
      strategy. Separation can be done on a cation-exchange column, where glyphosate
      elutes before AMPA, or on an anion-exchange column, where the elution order is
      reversed. Detection was achieved by using a fluorescent Al(3+)-morin postcolumn
      reagent. When the postcolumn reagent combines with the column effluent in a
      mixing tee, the fluorescence decreases in the presence of both analytes.
      Variables affecting the postcolumn indirect fluorescence detection were
      established and optimized; the major factors were postcolumn pH and volume and
      temperature of the postcolumn reaction coil. Detection limits, defined as three
      times the background noise, for glyphosate and AMPA separated on an anion
      exchange column were 14 and 40 ng, respectively.

PMID- 1400854
TI  - Direct serum injection in ion chromatography on packing materials with a semi
      permeable surface.
AB  - Reversed-phase packing materials with restricted access of proteins to the
      hydrophobic sites were tested for their applicability in the ion-interaction
      chromatography of anions. Especially C8-modified silica, which had been coated
      with a hydrophilic polymer acting as a semi-permeable barrier, could be used
      successfully for the separation of several anions in a proteinaceous matrix
      without removing the proteins prior to injection. In combination with UV or
      conductivity detection, this technique allows the determination of some
      physiologically important anions in serum samples.

PMID- 1400855
TI  - Analysis of oxyhalide disinfection by-products and other anions of interest in
      drinking water by ion chromatography.
AB  - The US Environmental Protection Agency is developing regulations for various
      drinking water disinfection by-products (DBPs). This effort involves developing
      analytical methods for the DBPs formed as a result of different disinfection
      treatments and collecting occurrence data for these species. Ion chromatography
      is one method being used to analyze drinking water samples for the following
      inorganic DBPs: chlorite, chlorate and bromate. These anions, however, are
      difficult to separate from common interfering anions of chloride, carbonate and
      nitrate. A method is therefore presented by which tetraborate/boric acid is used
      to separate these anions. Method detection limits of the order of 10
      micrograms/l, using conductivity and UV detection were obtained. Stability
      studies of chlorite showing the effectiveness of ethylenediamine as a
      preservative and summary data for an occurrence of nitrite, nitrate and the DBP
      precursor bromide are presented.

PMID- 1400856
TI  - New approach to the analysis of low levels of anions in water.
AB  - Optimized electromigrative sample introduction improves detection limits for
      anions in capillary electrophoresis. Reproducible results are achieved for
      micromolar and nanomolar levels of concentration. The new method offers shorter
      runtimes, improved resolution and greater simplicity in comparison with ion
      chromatography. The technique was applied to water samples from the power
      industry. Trace levels of anions are monitored routinely in water for steam
      generation in conventional and nuclear power plants. Reproducible and accurate
      results are presented for pure water samples containing typical concentrations of
      anions as well as for more specific types of samples, such as water compositions
      in the primary and secondary circuits of a nuclear power plant.

PMID- 1400857
TI  - Determination of creatinine and purine derivatives in ruminants' urine by
      reversed-phase high-performance liquid chromatography.
AB  - A procedure is described for the rapid and simultaneous determination of
      allantoin, creatinine, uric acid, hypoxanthine and xanthine in sheep urine.
      Separation was achieved on a Novapak C18 column under isocratic conditions. The
      mobile phase was potassium phosphate buffer (10 mM, pH 4.0). A flow-rate of 0.5
      ml/min, detection at 218 nm and a column temperature of 25 degrees C were
      employed with a total analysis time of less than 15 min. Detection limits for
      allantoin, creatinine, uric acid, hypoxanthine and xanthine were 1.0, 0.5, 0.5,
      0.5 and 0.2 micrograms/ml, respectively, at a signal-to-noise ratio of 3 in a 20
      microliters injection volume of tenfold-diluted urine. This sensitivity permits
      the precise determination of these compounds in ruminants' urine.

PMID- 1400858
TI  - Gas chromatographic retention of carbohydrate trimethylsilyl ethers. IV.
      Disaccharides.
AB  - Trimethylsilyl ethers of seventeen disaccharides were injected on two stationary
      phases and their retention indices were calculated. Multiple linear regression
      was used to discuss relationships between retention indices and structural
      features of disaccharides.

PMID- 1400859
TI  - Solid-phase extraction of prostanoids using an automatic sample preparation
      system.
AB  - A commercial automated solid-phase extraction system for cyclooxygenase
      arachidonic acid metabolites in urine samples has been evaluated. Comparison of
      manual and automatic batch (36 samples) extraction procedures for tritium
      labelled prostanoids added as tracers to urine samples has shown equivalent
      results with recoveries greater than 90% for prostaglandins E2, F2alpha and 6
      keto prostaglandin F1alpha as well as thromboxane B2. Analyte stability is not
      affected by the automated procedure, which uses less solvents and has a faster
      overall processing time than the manual method. The automated system has been
      applied to the extraction of prostanoids in urine samples from workers exposed to
      dichloroethane.

PMID- 1400860
TI  - Determination of the triglyceride composition of avocado oil by high-performance
      liquid chromatography using a light-scattering detector.
AB  - The triglyceride composition of avocado oil was determined by high-performance
      liquid chromatography using a light-scattering detector. Two avocado varieties,
      Fuerte and Hass, were analysed, and the qualitative composition of each was found
      to be similar, though quantitative differences were detected. The triglyceride
      composition was predicted using a system of equations based on the relationship
      between log k' and the molecular variables equivalent carbon number, chain length
      and number of double bonds for each of the fatty acids in the glycerides. A total
      of 24 molecular species of triglycerides were identified. The chromatographic
      system used successfully separated the critical pairs OOO-LOS, PaPaO-LnPP and
      PaOO-LOP (O = olein; L = linolein; S = stearin; Pa = palmitolein; Ln = linolenin;
      P = palmitin). Detector response was found to have a linear relationship with the
      amount of sample injected over the injection range 10-70 micrograms.

PMID- 1400861
TI  - Simultaneous determination of arsenic and antimony species in environmental
      samples using bis(trifluoroethyl)dithiocarbamate chelation and supercritical
      fluid chromatography.
AB  - Simultaneous separation and quantitation of arsenic(III) and antimony(III) can be
      achieved by extraction with lithium bis(trifluoroethyl)dithiocarbamate followed
      by supercritical fluid chromatographic (SFC) analysis. Arsenic(V) and antimony(V)
      are extracted after reduction with potassium iodide and sodium thiosulfate.
      Detection limits of 7 pg As and 11 pg Sb are achieved using this extraction
      method and SFC. Application to natural water and biological sample analysis is
      discussed.

PMID- 1400862
TI  - Gas chromatographic determination of the pesticide dodemorph for assessment of
      occupational exposure.
AB  - As part of a health hazard survey of occupational exposure to pesticides in
      greenhouse growing of ornamentals, analytical methods are developed and validated
      for measurement of exposure of workers to the fungicide dodemorph. A gas
      chromatographic method is developed using on-column injection and nitrogen
      phosphorus detection for quantification. Methods for the determination of
      (potential) dermal exposure by the analysis of foliar dislodgeable residues and
      cotton gloves are validated with respect to background, analytical recovery,
      stability, limit of detection, and between-day coefficients of variation.
      Analytical recovery from 'foliar dislodgeable residue solutions' and cotton
      gloves is more than 95%. Dodemorph in 'foliar dislodgeable residue solutions' and
      on cotton gloves is stable for at least five and six months, respectively, when
      stored in the refrigerator. Between-day coefficients of variation are 6% for both
      matrices. The limit of detection is 3 micrograms per leaf sample and 150
      micrograms per pair of gloves. Institute of Occupational Medicine (IOM) samplers,
      designed for the collection of a defined inspirable fraction of aerosols, are
      tested for sampling air-borne dodemorph. IOM samplers equipped with glass-fiber
      or cellulose filters appear unsuitable for reliable sampling of the fungicide
      because of breakthrough or breakdown during sampling.

PMID- 1400863
TI  - Long-term longitudinal measurements of plasma dehydroepiandrosterone sulfate in
      normal men.
AB  - Dehydroepiandrosterone sulfate (DS) was measured by direct tritium RIA in
      longitudinal plasma specimens from 97 normal healthy male participants in the
      Baltimore Longitudinal Study of Aging. Fasting blood was collected at regular
      visits (approximately 1.5 yr apart) over an average 13 yr of adulthood
      (cumulative age range: 32-83 yr). DS was measured in 3-4 widely spaced specimens
      from each subject. A decline in DS was found in 65 (67%) subjects, 13 subjects
      (13%) showed no change, and increases were found in the 19 remaining subjects
      during the study period. A plot of individual data points revealed the same
      pattern we had obtained previously from a cross-sectional study of a different
      normal male population. A plot of DS values vs. age among subjects whose DS
      increased during the study also revealed an age-related decline. Thus, the
      longitudinal decrease in circulating DS, long inferred from cross-sectional data,
      is confirmed for normal men in the present study. A more detailed study of every
      specimen collected during the study period from 12 of the Baltimore Longitudinal
      Study of Aging subjects (4 whose values tended to be low, 4 whose values tended
      to be high, and 4 whose values were near the mean) failed to reveal any patterns
      of variation that could be correlated with changes in life circumstances, health
      status, or any other discernible factors. Hence, the wide variability seen in DS
      among individuals within normal populations remains unexplained.

PMID- 1400864
TI  - Glucocorticoid receptor abnormalities in fibroblasts from patients with
      idiopathic resistance to dexamethasone diagnosed when evaluated for
      adrenocortical disorders.
AB  - A retrospective survey was accomplished on 420 consecutive patients who had
      undergone dexamethasone suppression tests between 1975-1988 due to suspected
      adrenal disorders. We found 7 patients in whom glucocorticoid resistance was
      apparent. They showed 4-6 abnormalities of the 7 investigations used:
      insensitivity to dexamethasone inhibition (n = 7), increased urinary cortisol (n
      = 3), glucocorticoid receptor (GR) thermolability (n = 4), decreased number of
      glucocorticoid receptors (n = 4), abnormal ligand affinity of GR (n = 4),
      abnormal basal GR mRNA expression (n = 4), and abnormal down-regulation of basal
      GR mRNA levels by dexamethasone (n = 1). The four patients with GR thermolability
      also showed increased basal GR mRNA levels. In the other patients the number of
      GR per cell was decreased without an up-regulation of GR mRNA. It is concluded
      that the syndromes of glucocorticoid resistance vary notably, clinically as well
      as biochemically; in patients evaluated for adrenocortical disorders the syndrome
      is apparently encountered in 1-2% of the patients.

PMID- 1400865
TI  - Abnormal norepinephrine and aldosterone responses to upright posture in
      nonmodulating hypertension.
AB  - The subgroup of patients with nonmodulating hypertension demonstrates a number of
      abnormalities of the renin-angiotensin-aldosterone axis. We previously identified
      abnormalities in plasma and urinary dopamine in nonmodulators and posited that
      this may be in part due to a generalized defect in sympathetic nervous system
      activity. In the present study we assessed the state of activation of the renin
      angiotensin system and the sympathetic nervous system in normal subjects and
      patients with modulating, nonmodulating, and low renin essential hypertension
      during sodium depletion and change from supine to upright posture. Levels of
      plasma norepinephrine were higher in non-modulators during the posture study (P <
      0.05). PRA rose with upright posture in all groups, but low renin subjects had a
      blunted response. Nonmodulators and low renin subjects had lower aldosterone
      levels both supine (P< 0.05) and upright (P< 0.01). However, the aldosterone/PRA
      increment ratio was increased in low renin subjects (P< 0.01), whereas it was
      decreased in nonmodulators. Twenty-four-hour urine collections for catecholamine
      determinations were obtained in a subgroup of the subjects, with nonmodulators
      showing higher levels of norepinephrine excretion which approached significance
      (P = 0.08). In vitro experiments using rat and human adrenal glomerulosa cells
      showed that norepinephrine does not affect aldosterone secretion per se. These
      observations extend the series of abnormalities observed in nonmodulating
      hypertension. However, it is likely that the alterations in norepinephrine levels
      during sodium depetion and upright posture are a secondary event and not linked
      to the altered aldosterone production in these patients.

PMID- 1400866
TI  - Prostate visualization studies in males homozygous and heterozygous for 5 alpha
      reductase deficiency.
AB  - Male pseudohermaphrodites with 5 alpha-reductase deficiency have ambiguous
      genitalia and nonpalpable prostates on rectal examination, suggesting the
      dihydrotestosterone dependency of these structures. To clearly delineate the
      status of the prostate, male pseudohermaphrodites with 5 alpha-reductase
      deficiency had transrectal sonography of the prostate performed, and the results
      were compared to that of age-matched male controls. In six male
      pseudohermaphrodites, magnetic resonance imaging studies of the prostate were
      also performed. Heterozygote fathers also had transrectal sonography of the
      prostate performed and the results compared to age-matched controls. The
      prostates of the male pseudohermaphrodites appeared as platelike soft tissue
      structures posterior to the urethra on both prostatic ultrasound and magnetic
      resonance imaging. Prostatic volume, as determined on prostatic ultrasound by two
      different methods, was significantly smaller (approximately one-tenth) than the
      volume of age-matched controls. Transurethral ultrasound guided biopsy of the
      prostate in two affected subjects revealed stromal tissue. These results
      correlate with undetectable prostate-specific antigen in affected subjects,
      suggesting atrophic epithelium or lack of epithelial differentiation. This study
      demonstrates the dihydrotestosterone dependence of the prostate for normal
      differentiation and growth. The presence of some prostatic tissue in the male
      pseudohermaphrodites may be due to the fact that there is a decrease and not an
      absence of 5 alpha-reductase activity, and/or that the increased level of
      testosterone in subjects with this condition partially compensates for the
      decreased level of dihydrotestosterone. There was no difference, however, in
      prostate size between heterozygous fathers and age-matched control males. The
      heterozygote fathers had dihydrotestosterone production sufficient for normal
      prostate growth and development.

PMID- 1400867
TI  - Contractile effects of prostaglandins, oxytocin, and endothelin-1 in human
      myometrium in vitro: refractoriness of myometrial tissue of pregnant women to
      prostaglandins E2 and F2 alpha.
AB  - Whereas there is much evidence in support of a role for prostaglandins (PG) in
      the parturitional process, it has not been demonstrated unequivocally that PGs
      are the physiological uterotonins involved in the induction of the myometrial
      contractions of spontaneous labor in women. This study was conducted to evaluate
      the contractile responsiveness of human myometrial tissue in vitro to PGs and to
      compare this response with that of other uterotonins, viz. oxytocin and
      endothelin-1. We found that treatment of uterine smooth muscle strips obtained
      from nonpregnant and pregnant women with PGE2 (10(-8)-10(-6) M) caused a biphasic
      response characterized by an initial single contraction of increased amplitude
      and duration, followed by relaxation and a long period (10-15 min) of quiescence.
      Conversely, PGE2 acted in rat myometrium to cause a monophasic response of
      increased contractile frequency and force. Whereas uterine smooth muscle from
      nonpregnant women was responsive to PGF2 alpha, the contractile responsiveness of
      myometrium from pregnant women was weak. This weak response to PGF2 alpha was
      found in myometrium of women in labor and in myometrium of women not in labor. 15
      Methyl-PGF2 alpha evoked a small response in myometrium from pregnant women.
      Under identical in vitro conditions, PGF2 alpha (10(-8)-10(-6) M) and 15-methyl
      PGF2 alpha (10(-6) M) caused sustained contractions in human vascular smooth
      muscle tissues (fetal aorta and arterial smooth muscle from chorionic vessels).
      Similarly, oxytocin and endothelin-1 (in myometrium from pregnant women) were
      effective in stimulating the force and frequency of myometrial contraction in
      vitro. We conclude that the myometrium of pregnant women, as evaluated in vitro,
      is refractory to the contractile effects of PGE2 and PGF2 alpha.

PMID- 1400868
TI  - Skeletal responsiveness to endogenous parathyroid hormone in postmenopausal
      osteoporosis.
AB  - To test the hypothesis that increased sensitivity of bone to PTH may be a major
      cause of bone loss in postmenopausal osteoporosis, we induced acute calcium
      deprivation and measured bone responsiveness to endogenous PTH under
      physiological conditions. Eighteen osteoporotic and 17 normal postmenopausal
      women with similar dietary calcium intakes were studied before and after 4 days
      of calcium deprivation (dietary calcium 230 mg/day and treatment with a calcium
      binding agent). Despite decreased serum PTH values, the baseline indices of bone
      turnover (serum osteocalcin level and 24-h urinary excretions of total
      deoxypyridinoline/creatinine and pyridinoline/creatinine corrected for total body
      bone mineral content), were higher in the osteoporotic women. During calcium
      deprivation, the changes in bone markers from baseline were similar in both
      groups, except for serum osteocalcin and serum type I procollagen carboxy
      terminal propeptide. Changes in the normal and the osteoporotic women were,
      respectively: serum ionized calcium concentration decreased 3.3% and 2.1%; serum
      intact PTH increased 65% and 56%; plasma 1,25-dihydroxyvitamin D3 increased 29%
      and 39%; pyridinoline/creatinine increased 12% and 11%; and
      deoxypyridinoline/creatinine increased 27% and 12%. Serum osteocalcin increased
      2.3% and serum procollagen carboxy-terminal propeptide decreased 9.4% in the
      normal women but did not change in the osteoporotic women. We conclude that women
      with postmenopausal osteoporosis do not have increased skeletal responsiveness to
      PTH compared with age-comparable normal postmenopausal women. Therefore, the
      higher bone turnover in postmenopausal osteoporosis, despite lower serum intact
      PTH concentration, must be due to other factors. Assessment of acute changes in
      bone turnover during physiological alterations in endogenous PTH secretion is a
      useful test in metabolic bone diseases.

PMID- 1400869
TI  - Correlations of language abnormalities with localization of mutations in the beta
      thyroid hormone receptor in 13 kindreds with generalized resistance to thyroid
      hormone: identification of four new mutations.
AB  - Generalized resistance to thyroid hormone is an inherited disease characterized
      by unresponsiveness of pituitary and peripheral tissues to thyroid hormone.
      Genetic analysis of several kindreds linked this syndrome to the gene for the
      beta-form of the thyroid hormone receptor, and this led to the subsequent
      identification of various mutations in the ligand-binding domain of this
      receptor. In this region we now have found 4 new point mutations with reduced T3
      binding affinities from separate kindreds by direct sequencing of polymerase
      chain reaction products. Similar to previously studied kindreds, the reduction in
      T3 binding of these four kindreds ranged from 2.5- to 5-fold, indicating that
      these are not neutral polymorphisms. Furthermore, the pattern of inheritance of
      these 4 kindreds is familial in 2, sporadic in 1, and unknown in 1. To date, 20
      distinct mutations have been identified, of which 18 are clustered in 2 distinct
      topographical regions: 11 are within the tau i/dimerization subdomains of exon 9,
      and 7 are within the L2 subdomain of exon 10. The 4 newly identified mutations
      coupled to the 9 mutations our laboratory has previously identified provide new
      insights into the clinical aspects of generalized resistance to thyroid hormone.
      Kindreds with mutations in exon 9 compared with those in exon 10 have
      significantly more problems in language development, as manifested by
      articulation problems and/or wide discrepancies in verbal and performance IQs.
      Interestingly, marked variability in language deficiency as well as other
      clinical patterns were seen not only between kindreds but also within a kindred.
      Further identification and clinical correlations of new mutations will continue
      to enhance our understanding of the structure/function relationships and
      physiological role of the human thyroid hormone receptor.

PMID- 1400870
TI  - Serum estradiol but not gonadotropin levels decrease acutely after insulin
      induced hypoglycemia in cycling women.
AB  - Although corticotropin-releasing hormone (CRH) acutely suppresses gonadotropin
      releasing hormone (GnRH) secretion in animal models, its effect on the
      hypothalamic-pituitary-gonadal axis in humans is not well defined. To further
      evaluate the acute effects of adrenal axis activation on the hypothalamic
      pituitary-gonadal axis in humans, we employed a model of insulin-induced
      hypoglycemia to stimulate endogenous CRH secretion in eight cycling women. Serum
      samples were obtained immediately before and 15, 30, 45, 60, 75, 90, and 120 min
      following iv insulin (0.15 U/kg) or saline injection. To ensure that the degree
      of hypothalamic-pituitary-adrenal activation in our subjects was similar to that
      observed in severely ill patients with hypogonadotropism, serum cortisol (F)
      levels were also measured in a group of acutely ill patients selected to have
      hypogonadotropism. All women experienced symptomatic hypoglycemia after insulin
      injection. Differences between serum F levels in hypoglycemic vs. control
      sessions were evident at 30 min (P < 0.01) and maximum at 120 min (P < 0.0001)
      after insulin injection. Serum estradiol levels were significantly lower
      following hypoglycemia than during control sessions (P < 0.001). In contrast,
      serum LH and FSH levels were not significantly different between control and
      hypoglycemic sessions. Peak serum F levels in these hypoglycemic women were
      similar to F levels in critically ill patients with hypogonadotropism. These
      results demonstrate that stress and/or hypoglycemia can acutely decrease
      circulating estradiol levels. In addition, these data suggest that endogenous CRH
      does not play a major role in acute suppression of GnRH (over 2 h) in humans.
      Further studies are required to identify longer term effects of CRH on GnRH
      secretion which may be present in hypothalamic amenorrhea or hypogonadotropic
      hypogonadism of critical illness.

PMID- 1400871
TI  - Longitudinal monitoring of bone mass accumulation in healthy adolescents:
      evidence for a marked reduction after 16 years of age at the levels of lumbar
      spine and femoral neck in female subjects.
AB  - The amount of skeletal mass acquired during adolescence is one of the most
      important determinants for the risk of postmenopausal and involutional
      osteoporosis. In both sexes, a large variance in bone mineral density (BMD) and
      content (BMC) is observed among healthy individuals at the beginning of the third
      decade. To determine the crucial pubertal years during which bone mass
      accumulation mainly occurs, we longitudinally monitored the gain in BMD/BMC at
      clinically important sites, such as lumbar spine and femoral neck, with respect
      to osteoporotic fracture risk. The changes in BMD (grams per cm2) and BMC (grams)
      were determined at 1-yr intervals at the level of lumbar spine vertebrae (L2-L4),
      femoral neck, and midfemoral shaft, using dual energy x-ray absorptiometry
      (Hologic QDR 1000), in 198 healthy adolescents (98 females and 100 males), aged 9
      19 yr. Mean daily energy and calcium intakes, height, weight, and body mass index
      of the studied cohort were within the normal range for age. In females, the
      increment rate in BMD/BMC was particularly pronounced over a 3-yr period, i.e.
      from 11-14 yr of age. This increment dramatically fell after 16 yr and/or 2 yr
      after menarche. The mean gains in lumbar, femoral neck, and midfemoral shaft BMD
      were not statistically significant between 17-20 yr. In males, the gain in
      BMD/BMC was particularly high over a 4-yr period, i.e. from 13-17 yr. Then the
      increment rate markedly declined, but remained significant between 17-20 yr for
      L2-L4 BMD/BMC and midfemoral shaft BMD. In contrast, no significant increase was
      observed for femoral neck BMD. An impressive interindividual variation was
      observed between the yearly height increment and the bone mass accumulation. The
      bone mass-height gains relationship during puberty evolved according to a loop
      pattern, with maximal variance at Tanner stages P3-P4. This longitudinal study
      delineates the crucial pubertal years during which the skeletal mass accumulates
      at high, but various, rates at skeletal sites where the consequences of the
      osteoporosis are particularly dramatic. Furthermore, the results indicate that in
      a cohort of healthy females with apparently adequate intakes of energy and
      calcium, bone mass accumulation is drastically reduced by 16 yr of age in both
      lumbar spine and femoral neck.

PMID- 1400872
TI  - Molecular analyses of a human sex hormone-binding globulin variant: evidence for
      an additional carbohydrate chain.
AB  - Genomic DNA was isolated from an individual who is homozygous for a sex hormone
      binding globulin (SHBG) variant that resolves into three molecular weight forms
      of 56K, 52K, and 48K during electrophoresis under denaturing conditions (sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis). This material was amplified
      using intron-specific oligonucleotide primers in a polymerase chain reaction to
      obtain the eight exons encoding SHBG. Sequence analysis of these exons revealed a
      point mutation encoding an amino acid substitution (Asp --> Asn) at residue 327
      in the SHBG polypeptide, and the same mutation was identified in three siblings
      who also appear to be homozygous for this trait. This mutation introduces an
      additional consensus site for N-glycosylation at this position, and to confirm
      its utilization we introduced it into a human SHBG complementary DNA. The mutated
      complementary DNA was inserted into the pRc/CMV expression vector, and
      transfected into Chinese hamster ovary (CHO) cells. The product was secreted
      normally but proportionally less of it (54%) bound to concanavalin A when
      compared to normal SHBG produced by CHO cells (85%), or SHBG in the serum of
      either a normal individual or those who produce an electrophoretic variant (98%).
      Furthermore, when subjected to sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and Western blotting, the SHBG variant produced by CHO cells
      consisted of a 60K subunit as well as the heavy (52K) and light (48K) subunits
      associated with normal SHBG produced by CHO cells or in serum. This additional
      subunit is larger than the variant in serum and probably reflects a greater
      degree of complexity in the carbohydrate structures added to recombinant SHBG
      during synthesis in CHO cells. Nevertheless, its steroid-binding affinity was
      equal to normal SHBG produced by CHO cells or SHBG in serum.

PMID- 1400873
TI  - Bromocriptine and Triac therapy for hyperthyroidism due to pituitary resistance
      to thyroid hormone.
AB  - Although a number of patients with generalized resistance to thyroid hormone have
      been treated with bromocriptine (Brc), only one previously reported patient with
      nontumoral TSH-mediated hyperthyroidism, presumably due to pituitary resistance
      to thyroid hormone (PRTH), has been successfully treated with bromocriptine
      (Brc). In addition, several studies suggested that the T3 analog 3,5,3'
      triiodothyroacetic acid (Triac) may control hyperthyroidism in patients with
      PRTH. In the current study a patient with PRTH diagnosed at age 15 yr underwent
      separate therapeutic trials with Brc and Triac, during which time physical
      parameters, thyroid function tests, systolic time intervals (STI), and oxygen
      consumption (VO2) were measured. On Brc therapy (12.5 mg/day), heart rate
      decreased (108 to 72/min), TSH decreased (5.7 to 1.2 mU/L), T3 decreased (9.9 to
      1.7 nmol/L), free T4 decreased (205 to 21 pmol/L), STI lengthened (left
      ventricular ejection time, 0.389 to 0.405 s), and VO2 did not change (164 to 162
      mL/min). We found no significant clinical improvement with a maximal dose of
      Triac (2.1 mg/day), only minimal reduction in goiter size; mild decreases in T3
      (9.9 to 6.7 nmol/L), free T4 (205 to 113 pmol/L), and TSH (5.7 to 5.4 mU/L); no
      change in STI (left ventricular ejection time, 0.389 to 0.401 sec); and an
      increase in O2 consumption (VO2, 164 to 209 mL/min). Thus, the results favor Brc
      as effective therapy for this patient with PRTH.

PMID- 1400874
TI  - Impaired stimulation of gluconeogenesis during prolonged hypoglycemia in
      intensively treated insulin-dependent diabetic subjects.
AB  - Defective glucose counterregulation commonly seen in intensively treated insulin
      dependent diabetes (IDDM) is mediated in part by a failure of compensatory
      stimulation of hepatic glucose production. Since the response of the liver to
      insulin-induced hypoglycemia normally involves activation of gluconeogenesis, we
      measured [14C]alanine conversion to [14C]glucose (a qualitative index of
      gluconeogenesis) and glucose production (using [3-3H]glucose) in seven
      intensively treated type I diabetic subjects (hemoglobin-A1, 7.1 +/- 0.4%) during
      low dose infusion of insulin (0.3 mU/kg.min for 210 min). IDDM patients received
      insulin overnight to maintain euglycemia before study. Although insulin levels
      rose to a similar extent as those in normal control subjects (n = 6), the fall in
      plasma glucose was markedly greater in IDDM (2.5 +/- 0.2 vs. 3.64 +/- 0.2 mM in
      controls; P < 0.01). The glucagon response was totally lost in IDDM, and
      epinephrine release was delayed and slightly reduced compared to that in control
      subjects. In contrast to that in normal subjects, hepatic glucose production in
      the IDDM subjects remained persistently suppressed by about 60% throughout the
      study. The conversion of alanine and lactate to glucose remained virtually
      unchanged in the IDDM, whereas in controls it increased 2-fold above baseline
      during the last hour of the study. Our data suggest that the failure of
      gluconeogenesis to increase during hypoglycemia is an important factor
      contributing to the defective hepatic response observed in the intensively
      treated type I diabetic subjects.

PMID- 1400875
TI  - Biosynthesis of interleukin-6 by cultured human chorion laeve cells: regulation
      by cytokines.
AB  - Intrauterine infection is an important cause of preterm labor and delivery and is
      characterized by increased production of inflammatory cytokines by gestational
      tissues. We evaluated the biosynthesis of the inflammatory cytokine interleukin-6
      (IL-6) by human chorion laeve cells and its regulation by other cytokines
      essential to the inflammatory process. We found that cultured chorion cells
      secrete IL-6 in the presence of growth medium supplemented only with 10% fetal
      calf serum. IL-1 beta, tumor necrosis factor, and lipopolysaccharide all induced
      a significant concentration-dependent stimulation of IL-6 production by chorion
      cells. The concentration range of each cytokine tested (0.1-10 ng/mL) is within
      the range of values found in the amniotic fluid of women destined to deliver
      preterm due to infection of gestational tissues. Additionally, treatment of
      chorion cells with IL-1 beta in combination with actinomycin-D or cycloheximide
      attenuated the stimulatory action of IL-1 beta on IL-6 production. Northern blot
      analysis of total RNA from cultured chorion cells stimulated with IL-1 beta
      demonstrated that IL-6 mRNA increases over time. Our data suggest that IL-6 is
      produced by human fetal chorion in response to infection of maternal gestational
      tissues. In conjunction with other inflammatory mediators, fetally derived IL-6
      may play a role in the pathophysiology of preterm labor due to infection.

PMID- 1400876
TI  - Spontaneous and stimulated growth hormone release in adolescents with type I
      diabetes mellitus: effects of metabolic control.
AB  - Abnormalities in GH release have been found in adults with poorly controlled type
      I diabetes mellitus. During puberty, circulating GH concentrations transiently
      increase. To investigate in pubertal diabetic adolescents, the physiological
      relationship between metabolic control and GH release, we compared spontaneous
      and GH-releasing hormone (GHRH)-stimulated GH release in six pubertal subjects
      during poor (study A) and improved (study B) metabolic control. The subjects
      included two females and four males (mean age +/- SE, 15.5 +/- 1 yr; duration of
      diabetes, 8.6 +/- 0.9 yr; Tanner stages II-V). Serum samples for glucose and GH
      determinations were obtained at 20-min intervals over a 24-h period. Significant
      pulses of GH release were identified using a pulse detection algorithm (Cluster).
      Fourier expansion time series was used to document the occurrence of significant
      periodicities in the GH concentration-time data series. All subjects received 1.0
      microgram/kg GHRH-44, iv, at 0800 h on the day after the 24-h monitoring for GH.
      After GHRH administration, samples were taken for glucose and GH determinations
      over 90 min. The overall mean glucose level (+/- SE) during the 24-h monitoring
      was 11.5 +/- 0.2 mmol/L during study A and 7.2 +/- 0.2 during study B (P =
      0.0001). During the 4 weeks of improved control, glycated hemoglobin fell from
      13.9 +/- 1.4% to 11.7 +/- 0.8% (mean +/- SE; P < 0.025). All subjects had
      significant pulses of GH release during poor or improved metabolic control.
      Relative to that at night, the daytime pulse frequency was higher in study A (P <
      0.025). The overnight pulse frequency increased during study B (P < 0.01). Other
      pulse parameters, including maximal and incremental pulse amplitudes, pulse
      width, and interpulse valley mean, did not change during improved control. The
      mean +/- SE 24-h GH concentration was 4.1 +/- 0.7 micrograms/L during study A and
      4.3 +/- 0.8 during study B. The amplitude of the circadian GH rhythm was not
      different by Fourier analysis. The overall mean glucose +/- SE after GHRH
      administration was 15.3 +/- 0.2 mmol/L in study A and 6.8 +/- 0.1 in study B. In
      spite of the marked hyperglycemia during study A, the GH responses were similar
      during studies A and B. Maximal GH levels were obtained at 15-30 min (mean +/-
      SE) and were 36.0 +/- 16.9 micrograms/L in study A and 38.7 +/- 18.9 in study
      B.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1400877
TI  - Effects of testosterone supplementation in the aging male.
AB  - Serum androgen levels decline with aging in normal males, such that a significant
      number of men over 60 yr of age will have a mean serum total testosterone (T)
      level near the low end of the normal adult range. It is not known whether lower T
      levels in older men have an effect on androgen-responsive organ systems, such as
      muscle, bone, bone marrow, and prostate, nor are there data to evaluate the
      relative benefits and risks of T supplementation in older men. We assessed the
      physiological and biochemical effects of T therapy in 13 healthy men, 57-76 yr
      old, who had low or borderline low serum T levels (< or = 13.9 nmol/L).
      Intramuscular testosterone enanthate (TE; 100 mg weekly) and placebo injections
      were given for 3 months each. Before treatment and at the end of both 3-month
      treatment regimens, lean body mass, body fat, biochemical parameters of bone
      turnover, hematological parameters, lipoprotein profiles, and prostate parameters
      [such as prostate-specific antigen (PSA)] were evaluated. Serum T levels rose in
      all subjects with TE treatment, such that the lowest level of T during a week's
      period was 19.7 +/- 0.7 nmol/L (mean +/- SE). After 3 months of TE treatment,
      lean body mass was significantly increased, and urinary hydroxyproline excretion
      was significantly depressed. With TE treatment, there was a significant increase
      in hematocrit, a decline in total cholesterol and low density lipoprotein
      cholesterol, and a sustained increase in serum PSA levels. Placebo treatment led
      to no significant changes in any of these parameters. We conclude that short term
      (3 months) TE supplementation to healthy older men who have serum T levels near
      or below the lower limit of normal for young adult men results in an increase in
      lean body mass and possibly a decline in bone resorption, as assessed by urinary
      hydroxyproline excretion, with some effect on serum lipoproteins, hematological
      parameters, and PSA. The sustained stimulation of PSA and the increase in
      hematocrit that occur with physiological TE supplementation suggest that older
      men should be screened carefully and followed periodically throughout T therapy.

PMID- 1400878
TI  - Serum propeptide and intact molecular osteocalcin in normal children and children
      with growth hormone (GH) deficiency: a potential marker of bone growth and
      response to GH therapy.
AB  - To establish a sensitive marker for bone formation we have developed a sandwich
      enzyme-linked immunosorbent assay for intact osteocalcin (OC) and its propeptide.
      Serum levels of these peptides were studied in 185 normal children, aged 4-15 yr,
      and in 23 GH-deficient children treated with GH. The serum levels of the
      propeptide in normal prepubescent children were 1.43 +/- 0.23 (mean +/- SE)
      micrograms/L in boys and 1.53 +/- 0.23 micrograms/L in girls. The peak value
      occurred at the age of 13 yr in boys (2.91 +/- 0.42 micrograms/L) and 11 yr in
      girls (2.34 +/- 0.34 micrograms/L). The serum intact OC levels in prepubescent
      boys and girls were 18.8 +/- 2.1 and 20.7 +/- 2.1 micrograms/L, respectively, and
      these levels increased to 41.0 +/- 3.7 micrograms/L in boys aged 13 yr and to
      27.0 +/- 2.5 micrograms/L in girls aged 11 yr. In the GH-deficient patients, a
      2.3-fold increase in the propeptide level and a 1.7-fold increase in the intact
      OC level was observed after 1 month of GH therapy. Serum propeptide and intact OC
      levels after 1 month of GH therapy correlated with the growth response after 12
      months of GH therapy (r = 0.660 and P < 0.01, for propeptide; r = 0.537 and P <
      0.01 for intact OC). These results show that since both propeptide and intact OC
      in serum were increased when the growth rate was elevated, these peptides are
      sensitive markers of bone formation. Serum levels of these peptides, particularly
      propeptide, after 1 month of GH therapy might be a helpful predictor of the
      growth response to long term GH therapy.

PMID- 1400879
TI  - Preliminary characterization of circulating amino- and carboxy-terminal fragments
      of parathyroid hormone-related peptide in humoral hypercalcemia of malignancy.
AB  - PTH-related peptide (PTHrP) immunoreactivity in plasma from six well
      characterized patients with humoral hypercalcemia of malignancy was characterized
      by gel filtration chromatography. An immunoradiometric assay directed against the
      N-terminal 74 amino acids of PTHrP and a RIA directed against the C-terminal
      region (amino acids 109-138) of the peptide were used to assay column fractions.
      When examined using acid (pH 5.0) nondenaturing conditions, N-terminal PTHrP
      immunoreactivity eluted with an apparent M(r) of 30,000-40,000. The apparent M(r)
      of this PTHrP fragment shifted to approximately 25,000 when gel filtration was
      performed at pH 9.0. The apparent M(r) shifted further, to approximately 6,500,
      when chromatographed under denaturing conditions in 4 M guanidine-HCl. Carboxy
      terminal PTHrP immunoreactivity in plasma eluted with an M(r) of approximately
      12,000 under acid nondenaturing conditions, as did the synthetic C-terminal PTHrP
      column marker, PTHrP (109-138). Synthetic PTHrP (1-36) and (1-74), and
      recombinant PTHrP (1-141) as well as native PTHrP species found in milk and
      keratinocyte-conditioned medium migrated in their expected positions when
      analyzed under alkaline nondenaturing or under denaturing condition. We conclude
      that native, synthetic, and recombinant PTHrP peptides may migrate anomalously
      when examined using gel filtration under nondenaturing conditions, and such
      studies should be interpreted with caution. Plasma from patients with humoral
      hypercalcemia of malignancy contains at least two PTHrP species. One native N
      terminal fragment appears, as assessed under denaturing conditions, to have an
      M(r) of approximately 6,500, and to therefore comprise approximately 50-60 amino
      acids of full-length PTHrP. A second chromatographically and immunologically
      distinct C-terminal fragment with an M(r) of approximately 12,000 under
      nondenaturing conditions is also present.

PMID- 1400880
TI  - Subcutaneous growth hormone-releasing hormone therapy in growth hormone-deficient
      children: first year of therapy.
AB  - The purpose of this study was to determine the efficacy and safety of GH
      releasing Hormone [GHRH-(1-44)] therapy in GH-deficient children. Twenty
      previously untreated prepubertal children with GHRH deficiency were treated for 1
      yr in a multicenter, open label, company-sponsored study with at least 20
      micrograms/kg GHRH-(1-44), sc, half at bedtime and half upon awakening. The main
      effects were enhancement of linear growth, advancement in bone age, and
      alteration in general blood chemistries and hormonal values. The mean velocity of
      the entire group increased from 3.6 +/- 1.1 to 8.1 +/- 1.5 cm/yr (P < 10(-4)) at
      1 yr of therapy. After 6 months of therapy, 16 were growing at a mean of 9.4 +/-
      2.0 cm/yr and were continued on this dose. In 4 patients who were growing at a
      rate of 5.5 +/- 1.7 cm/yr, the dose was increased to 40 micrograms/kg daily for
      the second 6 months. The high dose group increased their mean linear growth
      velocity for the second 6 months while on the higher dose to 7.6 +/- 0.4 cm/yr (P
      < 10(-2)). This was equal to the mean velocity for the second 6 months of therapy
      of the 16 subjects who remained on the 20 micrograms/kg daily therapy (7.6 +/-
      1.2 cm/yr). Mean advancement of bone age was 1.3 +/- 0.6 yr during the first year
      of therapy. No adverse changes in general biochemical, hormonal, or pituitary
      radiographic analyses were noted. No change in fasting glucose or insulin
      concentrations, or excessive generation of insulin-like growth factor-I
      concentrations occurred. We conclude that GHRH in a daily dose of 20-40
      micrograms/kg for 1 yr was effective in increasing growth velocity in most GHRH
      responsive GH-deficient patients. It was well tolerated without side-effects.
      Glucose intolerance was not noted.

PMID- 1400881
TI  - Acute growth hormone (GH) response to GH-releasing hexapeptide in humans is
      independent of endogenous GH-releasing hormone.
AB  - The synthetic GH-releasing hexapeptide (GHRP: His-DTrp-Ala-Trp-DPhe-Lys-NH2)
      releases GH in man by an undetermined mechanism. To investigate whether acute GH
      response to GHRP is mediated by endogenous GHRH, we examined the effect of GHRP
      on GH release during pituitary desensitization to GHRH induced by short-term GHRH
      infusion. In five healthy men on six occasions, we infused saline (sal) or 1
      microgram/kg.h GHRH-44 for 6 h. After 4 h, a bolus of sal, GHRH-44 1 microgram/kg
      body weight, or GHRP 1 microgram/kg body weight was given iv. GH concentration,
      measured by RIA, was analyzed by mean area under the curve (AUC) of GH released
      over the 2 h immediately after bolus injection. Infusion of GHRH had a biphasic
      effect on GH release; plasma GH increased to 12.7 +/- 3.3 micrograms/L within the
      first hour, with subsequent decrease to 2.9 +/- 0.3 micrograms/L during the last
      2 h of infusion. GH AUC (hours 4-6 of infusion) microgram/L.2 h [table: see text]
      GH response to bolus GHRH was abolished by GHRH infusion, whereas GH response to
      GHRP persisted under the same conditions. Thus, we conclude that acute GH
      response to GHRP in humans is not mediated by endogenous GHRH.

PMID- 1400882
TI  - Role of body fat distribution in the decline in insulin sensitivity and glucose
      tolerance with age.
AB  - The relationships of body composition and physical fitness [maximal aerobic
      capacity (VO2max)] to the decline in insulin sensitivity with age were examined
      in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older
      men with normal glucose tolerance (OGTT), glucose disposal rates (M) during
      hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip
      ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and
      positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar
      relationships existed in the 36 older men with a spectrum of OGTT responses;
      however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the
      older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free
      mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS).
      Furthermore, in older and young men with normal OGTT matched for WHR, percent
      fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals
      during the clamp and in its relationship to insulin concentrations at the tissue
      level (multicompartmental analysis). In contrast, despite higher steady state
      plasma insulin levels during the clamp, M was significantly lower in the older
      men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus,
      in healthy older men up to the age of 73 yr, insulin sensitivity and glucose
      tolerance are affected primarily by the regional body fat distribution, not age,
      obesity, or VO2max.

PMID- 1400883
TI  - Cloning and in vitro expression of the human selenoprotein, type I iodothyronine
      deiodinase.
AB  - The type I 5' iodothyronine deiodinase (5' DI) catalyzes the deiodination of T4
      to the biologically active hormone T3 and accounts for a significant fraction of
      its production. We have recently cloned the complementary DNA (cDNA) for the rat
      5' DI, which contains the rare amino acid selenocysteine, and used this to screen
      human liver and kidney cDNA libraries to identify a human 5' DI cDNA clone. From
      these, we constructed a cDNA encoding a functional 5' DI. The 2222 base pair
      human 5' DI cDNA is approximately 200 nucleotides shorter than the 2.4-kilobase
      hybridizing band in Northern blots of human liver, kidney, and thyroid, because
      of missing 5' untranslated sequence and the poly A tail. The deduced amino acid
      sequence codes for a protein of 28.7 kilodaltons assuming the UGA codon at
      position 382 encodes selenocysteine, and is highly homologous (88% similarity) to
      the rat. We transiently expressed the 5' DI in COS-7 cells to establish that it
      encodes a functional enzyme and to study its kinetics. These show saturable
      deiodination of rT3 (Ka 0.52 +/- 0.04 mumol/L and Vmax 63.2 +/- 16.4 pmol min-1
      mg-1). T4 and gold thioglucose are competitive inhibitors of rT3 deiodination. 6
      n-Propylthiouracil (PTU) is an uncompetitive inhibitor (with rT3) and competitive
      inhibitor (with dithiothreitol) of rT3 deiodination. 6-n-Propylthiouracil
      inhibits T4 to T3 conversion. Labeling of COS-7 cells transiently transfected
      with the human 5' DI cDNA with bromoacetyl-125I-T3 demonstrates a 28-kilodalton
      protein. This indicates that in the human, as well as in the rat messenger RNA,
      the UGA encodes selenocysteine and translation terminates at the UAA codon at
      nucleotides 754 to 756. Reverse T3 and gold thioglucose (100 nmol/L) block
      bromoacetyl-125I-T3 labeling of the transiently expressed human and rat 5' DI
      proteins. These results demonstrate that the human 5' DI is a selenoprotein,
      analogous to the rat enzyme. Given the previously demonstrated critical role of
      the selenium atom in catalyzing deiodination by this protein, we conclude that
      this trace element is essential for normal thyroid hormone action in man.

PMID- 1400884
TI  - The expression of human chorionic gonadotropin/human luteinizing hormone
      receptors in ectopic human endometrial implants.
AB  - Our laboratory previously demonstrated that normal human endometrium contains
      hCG/human LH receptors. Since ectopic endometrial implants in endometriosis arise
      directly at least in part from uterine endometrium, we investigated whether the
      implants continue the expression of these receptors. The presence of hCG/LH
      receptor mRNA and/or immunoreactive receptor protein in ectopic endometrial
      implants on pelvic peritoneum, uterine endometrium, and unaffected or normal
      peritoneum from patients with (n = 12) and without (n = 14) clinically apparent
      endometriosis was examined by in situ hybridization and immunocytochemistry
      analyses. The results showed that the peritoneal biopsies with visible or
      microscopic endometrial implants contain receptor mRNA and receptor protein. The
      glands contain more receptor mRNA and receptor protein than stromal cells in
      implants similar to uterine endometrium from patients with or without
      endometriosis. However, there is no consistent difference in the expression of
      receptors in implants compared to uterine endometria from patients with or
      without endometriosis. Contrary to ectopic endometrial implants, unaffected or
      normal peritoneum contain neither receptor mRNA nor receptor protein. In summary,
      we conclude that ectopic endometrial implants contain hCG/LH receptor mRNA and
      receptor protein, which suggests new possibilities in the medical treatment of
      endometriosis.

PMID- 1400885
TI  - Epithelial hyperplasia and decreased colloid content of the thyroid gland in
      triiodothyronine-predominant Graves' disease.
AB  - Patients with T3-predominant Graves' disease have an increased serum T3 level
      despite a normal or even lower level of serum T4 caused by antithyroid drug
      treatment. This study investigated the morphological characteristics of the
      thyroid gland in this type of hyperthyroidism. Ultrasound showed a similar
      thyroid echogenicity in both T3-predominant and ordinary Graves' disease, but
      thyroid weight was significantly greater in T3-predominant Graves' disease than
      in the controls [91 +/- 37 g vs. 48 +/- 17 g (mean +/- SD); P < 0.01]. The height
      of thyroid follicular epithelial cells were significantly greater in T3
      predominant Graves' disease than in the controls (9.6 +/- 1.0 vs. 6.4 +/- 1.1
      microns), but the epithelial height did not correlate significantly with the
      serum TSH receptor antibody titers. Epithelial cells occupied 26.4 +/- 10.9% of
      the total thyroid tissue in T3-predominant Graves' disease, while they occupied
      only 14.5 +/- 6.8% in the controls. Intracolloidal vacuoles also occupied a
      significantly greater area in the T3-predominant group (6.6 +/- 3.9% vs. 1.9 +/-
      1.0% for controls). These findings suggest that the thyroid gland is more active
      in T3-predominant Graves' disease and has a more rapid turnover of intrathyroidal
      iodine than in the ordinary type of Graves' disease.

PMID- 1400886
TI  - Histomorphological and immunohistochemical evidence that human nodular goiters
      grow by episodic replication of multiple clusters of thyroid follicular cells.
AB  - This study was aimed at dissecting the cellular mechanisms that underly the
      growth of actively expanding human goiter nodules. Thirty-two nodules from
      different patients, all removed because of steady recent growth, were serially
      sectioned and screened for 1) histomorphological signs of cell proliferation and
      2) in situ expression of the immunohistochemically stained p21ras protooncogene
      product. Bovine, porcine, and rat thyroid glands (the latter from both T4- and
      perchlorate-treated animals) were used as controls. In normal glands, only a few
      follicular cells contain substantial amounts of stainable p21ras. Some of these
      cells are unusually large, but do not proliferate. In contrast, all goiter
      nodules contain areas where the epithelial cells are morphologically grossly
      altered and heavily loaded with p21ras. Cells of this type are mostly clustered
      in large cohorts coating whole follicles or entire groups of follicles. Only a
      small fraction of these activated cells actually proliferates at any one point in
      time. Actively replicating cells are scattered in tiny foci all over the nodules.
      The earliest proliferating buds are solid, but soon begin to generate
      microfollicles that enlarge by adding new cells to the follicular epithelium.
      Regionally heterogeneous p21ras content in morphologically identical cells
      suggests that growth occurs in bursts and waves. We conclude that goiter nodules
      grow by episodic proliferation of heterogeneous cohorts of epithelial cells from
      which new follicles are generated. Only a tiny fraction of all goiter cells
      proliferate at any one point in time. The molecular mechanisms governing these
      growth processes are unknown.

PMID- 1400887
TI  - Evidence for the presence of the estrogen receptor in the ovary of the baboon
      (Papio anubis).
AB  - Although intraovarian estrogen has been firmly established as an important factor
      in the regulation of ovarian follicular development and function in the rat, an
      autocrine-paracrine role for estrogen in the primate ovary is not yet
      established. Immunocytochemical identification of an estrogen receptor in the
      monkey follicle was negative, but it was positive for the granulosa cells of
      antral follicles of the human ovary. In the present study baboon ovaries obtained
      during the follicular phase were examined for the presence of estrogen receptor
      by immunocytochemical analysis of frozen sections and Northern blot analysis of
      RNA extracts of the ovaries. Immunocytochemistry identified the estrogen receptor
      in the granulosa cells of healthy appearing and atretic or cystic-like antral
      follicles and in occasional, but rare, thecal cells. The ovaries contained a
      prominent mRNA species for the estrogen receptor, approximately 7 kilobases in
      size, which was present in relatively low abundance compared to that in the
      nonpregnant baboon uterus, but in a similar abundance to the estrogen receptor
      mRNA content of the pregnant endometrium. These studies are the first to report
      the presence of estrogen receptor mRNA in the ovary of a primate. These results
      in conjunction with the immunocytochemical studies firmly establish the presence
      of the estrogen receptor in the primate ovary and suggest an autocrine-paracrine
      role for intraovarian estrogen in primate ovarian physiology.

PMID- 1400888
TI  - Atypical McCune-Albright syndrome associated with growth hormone-prolactin
      pituitary adenoma: natural history, long-term follow-up, and SMS 201-995-
      bromocriptine combined treatment results.
AB  - A 35-yr-old woman is described as having atypical McCune-Albright syndrome,
      associated with acromegaly and hyperprolactinemia due to pituitary adenoma. The
      patient did not present sexual precocity, but primary amenorrhea. After
      transphenoidal adenomectomy, the GH plasma levels returned to normal, whereas the
      PRL values decreased; bromocriptine therapy normalized PRL levels and induced
      ovulatory menses. After 4 uneventful yr the patient developed relapse of active
      acromegaly that did not recover after a second neurosurgical exploration.
      Bromocriptine treatment maintained normal PRL levels but did not significantly
      reduce GH ones; the association with long-acting somatostatin analog SMS 201-995
      by continuous sc pump infusion induced definitive control of GH and somatomedin-C
      secretion. These results suggest an additive inhibitory effect on GH secretion
      exerted by the two drugs.

PMID- 1400889
TI  - Precocious puberty in girls: pituitary height as an index of hypothalamo
      pituitary activation.
AB  - The pituitary heights in 47 girls having breast development before 8 yr were
      measured by magnetic resonance imaging and compared to the normal values for age
      and to clinical and laboratory data. They were classified into 3 groups: 1)
      premature thelarche (PT), isolated breast development with plasma estradiol less
      than 74 pmol/L (8 cases); 2) mild form of central precocious puberty (CPP1) with
      an LH/FSH peak ratio after the LH-releasing hormone test less than 1 (22 cases);
      3) classical form of CPP (CPP2) with an LH/FSH peak ratio greater than 1 (17
      cases). All girls with CPP had breast and pubic hair development before 8 yr,
      accelerated growth velocity, and no intracranial lesion. The mean ages at breast
      development [7.2 +/- 0.4 (SE), 6.5 +/- 0.4, and 7.2 +/- 0.3 yr] and the mean
      times between breast development and magnetic resonance imaging evaluation (0.8
      +/- 0.1, 0.8 +/- 0.2, and 0.9 +/- 0.1 yr) were similar in the 3 groups. The mean
      pituitary heights were 4.9 +/- 0.2 in PT, 5.1 +/- 0.2 in CPP1, and 6.2 +/- 0.2 mm
      in CPP2. They were not significantly different in PT and CPP1 but were
      significantly greater in CPP2 than in PT (P < 0.001) or CPP1 (P < 0.001).
      Individual values of pituitary height were compared to those of age-matched
      girls: they were greater than or equal to mean +/- 2 SD in 8% of PT, 32% of CPP1,
      and 70% of CPP2. In the CPP group, the pituitary height was correlated with the
      LH/FSH peak ratio [correlation coefficient (r = 0.52, P < 0.01] and plasma
      estradiol (r = 0.60, P < 0.01). Four patients with high pituitary height despite
      LH/FSH peak ratios less than 1 had an increase of their breast development within
      1 yr. We conclude that the pituitary height is normal for age in girls with
      premature thelarche or a mild form of CPP. Conversely, pituitary height is in the
      pubertal range in girls with the classical form of CPP. Its correlation with
      LH/FSH peak ratio suggests that pituitary height reflects changes in the degree
      of hypothalamo-pituitary activation and may provide an indication of its future
      development. It may therefore help in decisions on LH-releasing hormone analog
      therapy in certain cases.

PMID- 1400890
TI  - Parathyroid hormone-related protein mRNA in avascular human amnion.
AB  - Previously, we found that preproendothelin-1 mRNA is present in human avascular
      amnion tissue. In this investigation, we evaluated the possibility that another
      vasoactive protein, namely, parathyroid hormone-related protein (PTH-rP), also is
      produced in amnion. Using a specific cDNA probe, we identified PTH-rP mRNA in
      amnion tissue and found that the level of PTH-rP mRNA in placental amnion was
      greater than that in reflected amnion tissue obtained from the same pregnancy.
      PTH-rP mRNA also was demonstrable in chorion laeve and in decidua, but the levels
      of this mRNA in these tissues were much lower than that in amnion. By
      radioimmunoassay, we found that human amnion cells in primary monolayer culture
      secrete immunoreactive PTH-rP into the medium. Importantly, the placental amnion
      covers the chorionic vessels that traverse over the chorionic plate prior to
      branching into the cotelydons; specifically, there is no intervening tissue
      between placental amnion and the adventitial tissue of the chorionic vessel wall.
      Thus, the potential exists for the production of endothelin-1, a potent
      vasocontractant, and PTH-rP, a vasorelaxant, in placental amnion for export to
      the adventitial surface of the chorionic vessels. Moreover, amnion cells respond
      to a number of agents (e.g., transforming growth factor-beta) that effect changes
      in the expression of these two peptides. Therefore, the possibility should be
      considered that amnion-derived vasoactive proteins may modulate fetal chorionic,
      umbilical, and villous vessel tone and thereby fetal-placental blood flow.

PMID- 1400891
TI  - Clinical review 38: Intensive management of insulin dependent diabetes: risks,
      benefits, and unanswered questions.

PMID- 1400892
TI  - Interrelationships between the renin-angiotensin-aldosterone and calcium
      homeostatic systems.
AB  - Blood pressure is affected by both sodium and calcium intake. To determine if
      there is an interaction between the regulatory mechanisms for these two cations,
      eight normal male volunteers received the following 1-h infusions on three
      different days: 1) angiotensin II (AII), 2) the synthetic 1-34 amino terminal
      fragment of human PTH [hPTH(1-34)], and 3) AII and hPTH(1-34) together. Blood
      samples were obtained at t = 0 and every 20 min during each infusion and urine
      was collected for 3 h both before and after the start of each infusion. Infusion
      of AII produced an increase in intact PTH from 18 +/- 2 to 31 +/- 4 ng/L (P <
      0.05), most likely in response to a small decrease in serum ionized calcium (1.25
      +/- 0.01 to 1.23 +/- 0.01 mmol/L, P < 0.05). Urinary excretion of calcium was
      unchanged. Infusion of hPTH(1-34) at 200 U/h increased N-terminal PTH levels (18
      +/- 3 to 268 +/- 42 ng/L, P < 0.05), decreased tubular reabsorption of phosphate
      (0.92 +/- 0.03 to 0.82 +/- 0.11, P < 0.05), and increased urinary cAMP (0.18 +/-
      0.02 to 0.53 +/- 0.05 nmol/L of glomerular filtrate, P = 0.0001). hPTH(1-34)
      infusion suppressed endogenous intact PTH (18 +/- 3 to 14 +/- 2 ng/L, P < 0.005)
      and increased PRA from 0.14 +/- 0.02 to 0.32 +/- 0.05 ng/(L.s) (P < 0.05) without
      a change in serum ionized calcium which suggests direct effects of hPTH(1-34) on
      the parathyroid glands and the juxtaglomerular apparatus. The effects of AII and
      hPTH(1-34) were antagonistic with little change in serum ionized calcium, intact
      PTH, or PRA when both were infused together. These interrelationships between the
      major hormonal systems controlling sodium and calcium homeostasis suggest a
      mechanism underlying the close association of calcium and sodium in the
      regulation of blood pressure.

PMID- 1400893
TI  - Abrogation by a potent gonadotropin-releasing hormone antagonist of the
      estrogen/progesterone-stimulated surge-like release of luteinizing hormone and
      follicle-stimulating hormone in postmenopausal women.
AB  - In both the rodent and primate, administration of progesterone elicits an acute
      surge-like release of LH in the setting of prior estrogen treatment. Whether
      these facilitative effects of estrogen and progesterone on gonadotropin secretion
      reside at pituitary or hypothalamic loci is not known. To further investigate the
      mechanisms by which estrogen combined with progesterone amplifies gonadotropin
      secretion, we studied the responses of seven estrogen-primed postmenopausal women
      to progesterone administration with or without cotreatment with a potent GnRH
      antagonist, [Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA), DAla10]GnRH. Repetitive
      blood sampling for the later measurement of serum concentrations of LH, FSH, and
      PRL was begun 4 h before the administration of progesterone and continued for 36
      h. We observed that progesterone administration after 72 h of priming with
      ethinyl estradiol resulted in a surge-like release of LH and FSH in all subjects.
      Concomitant administration of the GnRH antagonist abolished the surge-like
      release of both gonadotropins in all subjects. In contrast, administration of the
      antagonist had no effect on PRL release. These results indicate that endogenous
      GnRH action is an obligatory component of the progesterone-induced surge-like
      release of both gonadotropic hormones in the estrogen-primed human.

PMID- 1400894
TI  - Mineral metabolism in Turner's syndrome: evidence for impaired renal vitamin D
      metabolism and normal osteoblast function.
AB  - We examined intact PTH and 1,25-dihydroxyvitamin D [1,25-(OH)2D] in both baseline
      and dynamic conditions (low calcium diet) in 14 patients with Turner's syndrome
      (mean age, 12.6 +/- 5.9 yr; range, 4.2-21.0 yr) and bone demineralization as well
      as in a control group of 15 healthy girls (mean age, 12.8 +/- 5.6 yr; range, 3.8
      22.7 yr). In both groups we also measured osteocalcin serum levels in response to
      oral 1,25-(OH)2D3 administration (1.8 micrograms/m2/daily for 6 days) to assess
      osteoblast function. The low calcium diet decreased ionized calcium (Ca2+) levels
      and elevated PTH values to the same extent in both patients (Ca2+, -8.40 +/-
      3.78%; intact PTH, +47.88 +/- 13.24%) and controls (Ca2+, -9.09 +/- 3.25%; intact
      PTH, +52.77 +/- 10.52%; P = NS vs. patients). While controls showed an increment
      in their serum 1,25-(OH)2D levels (+52.15 +/- 8.95%), patients did not (+10.93 +/
      4.71%; P = NS vs. baseline; P < 0.001 vs. controls). 1,25-(OH)2D3 administration
      caused a rise in the serum osteocalcin levels in a similar fashion in both groups
      (peak values: patients, +35.38 +/- 7.20%; controls, +34.09 +/- 7.98%; P = NS). We
      conclude that in patients with Turner's syndrome there is an altered renal
      vitamin D metabolism in response to physiological stimulus, while osteoblast
      function in response to 1,25-(OH)2D3 administration is not affected.

PMID- 1400896
TI  - Bullous pemphigoid autoantibodies reactive with intracellular basal keratinocyte
      antigens: studies of subclass distribution and complement activation.
AB  - Using immunofluorescence (IF) and monoclonal antibodies (MoAbs) to IgG
      subclasses, terminal complement components, and S-protein/vitronectin, we have
      extended recent observations concerning reactivity of bullous pemphigoid
      autoantibodies with intracellular antigens located on the polar tips of basal
      human keratinocytes (HuK). Using three purified bullous pemphigoid IgG fractions,
      autoantibody reactivity with these intracellular antigens was present in all four
      IgG subclasses. When skin sections were used as substrate, an identical IgG
      subclass distribution of autoantibodies for each bullous pemphigoid IgG fraction
      was observed, but reactive with the basement membrane zone. All three bullous
      pemphigoid IgG preparations contained IgG subclass autoantibodies capable of
      complement fixation. Each IgG fraction resulted in fixation of all of the
      terminal complement components (C5, C6, C7, C8, and C9) and assembly of the
      membrane attack complex (MAC) on the polar tips of basal HuK. S
      protein/vitronectin was not bound in a similar fashion. Normal IgG fractions
      yielded consistently negative reactions. Thus, bullous pemphigoid autoantibodies,
      fixed to polar tips of basal HuK, are found in all four IgG subclasses and will
      activate complement resulting in generation of MAC.

PMID- 1400895
TI  - Superantigens: biology, immunology, and potential role in disease.
AB  - Superantigens are unique products of bacteria and viruses which, in combination
      with class II major histocompatibility complex molecules, are capable of
      stimulating a large fraction of T cells in an affected individual. This
      stimulation primarily involves the variable region of the T cell receptor beta
      chain (V beta). The discovery of superantigens and the elucidation of their
      immunologic properties have provided valuable tools for the investigation of the
      immune system in both normal and diseased animals. Most importantly, recent work
      suggests that superantigens play a role in a number of diverse pathological
      conditions, including toxic shock syndrome and autoimmune diseases such as
      rheumatoid arthritis.

PMID- 1400898
TI  - Indeterminate western blot patterns in a cohort of individuals at high risk for
      human immunodeficiency virus (HIV-1) exposure.
AB  - Our objective was to map serial patterns of Western blot reactivity over time of
      a cohort of initially ELISA-negative, Western blot-indeterminate individuals from
      a high-risk group and to determine if these individuals were at increased risk of
      harboring occult HIV-1 infection. A 2-year prospective study used serial ELISA,
      two types of Western blot, immunologic profiles, HIV-1 culture, and analysis by
      polymerase chain reaction. Subjects were 20 ELISA-negative, Western blot
      indeterminate homosexual volunteers and 20 matched seronegative controls. Results
      showed that 19 of 20 study subjects completed a mean of 17.0 months of clinical
      and laboratory follow-up. Reactivities with p24 and/or with p55 were the two most
      commonly observed Western blot patterns, occurring in 70% of individuals.
      Specific Western blot reactivity was dependent upon the particular immunoblot
      preparation being used and varied considerably on a longitudinal basis. No
      individual pattern appeared predictive of an increased likelihood of subsequent
      seroconversion to HIV-1 relative to controls. By all other criteria including
      polymerase chain reaction analysis, samples from 17 of 19 individuals remained
      negative for HIV-1 at each time point. Two individuals evolved from an
      indeterminate to a positive Western blot and, simultaneously, from a negative to
      a positive polymerase chain reaction analysis, during follow-up. Our conclusions
      were as follows. ELISA-negative, Western blot-indeterminate individuals from a
      high-risk group show marked variability in immunoblot findings over time, and
      these patterns do not appear predictive of an increased likelihood of
      infection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400897
TI  - Cytokine release and dynamics of leukocyte populations after CD3/TCR monoclonal
      antibody treatment.
AB  - Cytokine release and clinical side effects resulting from the use of OKT3 and BMA
      031 monoclonal antibodies in the treatment of kidney graft recipients were
      evaluated and compared. The rise observed in serum levels of interferon gamma.
      TNF alpha, and IL-8 was similar after administration of either monoclonal
      antibody. Furthermore, both OKT3 and BMA 031 resulted in rapid disappearance not
      only of virtually all T cells, but also of substantial percentages of all major
      leukocyte populations from the circulation; this effect is probably due to
      cytokine release activating endothelial cells and thereby causing extravasation
      even of leukocytes not specifically recognized by the administered antibodies.
      Evidence has thus been obtained that BMA 031 is as potent as OKT3 in inducing
      unequivocal signs of T cell activation in vivo. However, while OKT3 therapy was
      accompanied by adverse side effects in our study as in previous ones, we saw no
      such reactions in any of the patients receiving BMA 031. This contrast might be
      due to different mechanisms of leukocyte activation possibly inducing other
      mediators in the case of OKT3, which then, in combination with the cytokines,
      could generate treatment-associated morbidity.

PMID- 1400899
TI  - Accelerated expression of secreted alpha-chain gene in anaphylactoid purpura.
AB  - The mechanisms of the elevation of serum IgA levels in anaphylactoid purpura were
      investigated. Serum IgA levels were significantly elevated within 2 weeks (5 to
      14 days for all 12 patients) after onset in patients with anaphylactoid purpura.
      Serum IgM and IgG were not elevated. Although the percentages of surface IgA
      bearing cells were not increased in the patients, the numbers of IgA-secreting
      cells within 2 weeks after onset in the patients with anaphylactoid purpura were
      significantly higher than those of controls. In northern blot analysis on
      lymphocytes, the secreted alpha (alpha s)-chain gene was well expressed compared
      with the membrane-bound alpha (alpha m)-chain gene, within 2 weeks after the
      onset of anaphylactoid purpura. Therefore, stimulation by a certain agent or a
      certain immune response may accelerate expression of the alpha s-chain gene in
      anaphylactoid purpura.

PMID- 1400900
TI  - Elevated serum interleukin-6 levels in patients with acute hepatitis.
AB  - To study the mechanisms of hepatocyte injury, we examined serum interleukin-6 (IL
      6) level in acute hepatitis patients. Based on their clinical features, these
      patients were divided into three groups, acute hepatitis (AH), severe acute
      hepatitis, and fulminant hepatic failure (FHF). The present study demonstrated
      that, in association with their clinical status, their serum IL-6 levels were
      gradually increased (16.5 +/- 14.5 pg/ml in AH, 26.3 +/- 19.0 pg/ml in severe AH,
      and 470.2 +/- 261.4 pg/ml in FHF; control level, 5.2 +/- 0.6 pg/ml). Furthermore,
      we found that a significant correlation between serum IL-6 level and prothrombin
      time existed in these patients and that the elevated serum IL-6 returned to a
      normal range after recovery from their hepatocyte injury. Thus, our study
      demonstrates that the serum IL-6 level is a possible marker for identifying the
      clinical status in acute hepatitis and that this cytokine may have some roles in
      hepatocyte injury.

PMID- 1400901
TI  - Antimitochondrial (pyruvate dehydrogenase) autoantibodies in autoimmune rheumatic
      diseases.
AB  - Anti-pyruvate dehydrogenase (PDH) antibodies were determined in 1451 sera of
      patients with primary biliary cirrhosis (PBC) and several autoimmune rheumatic
      conditions by ELISA and immunoblotting. They were detected in sera of 93% of the
      patients with PBC (179 of 192 patients) in 60 of 277 (22%) patients with
      Sjogren's syndrome (SjS), 34 of 437 (8%) patients with scleroderma, 33 of 191
      patients with SLE (17%), and 5 of 55 (10%) patients with rheumatoid arthritis
      (RA) but in none of the patients with polymyositis or the antiphospholipid
      syndrome. The ELISA studies were confirmed by immunoblots showing binding of
      autoimmune rheumatic sera to the same epitope (74 kd) of mitochondria that the
      PBC sera reacted with. The identical binding characteristics were also confirmed
      by protein competition assays with purified PDH. In 4 of 53 patients with SjS who
      were positive for anti-PDH, high titers as in PBC were detected. The anti-PDH
      antibodies in Sjogren's patients were associated with deranged liver function
      tests and extraglandular features but did not correlate with any other non-organ
      specific antibody. Follow-up studies confirmed the association of the emergence
      of anti-PDH antibodies with defects in liver function tests. The antibodies were
      more prevalent in SLE and RA when they were associated with Sjogren's syndrome
      (30 and 18.8%, respectively). Among patients with different forms of scleroderma,
      anti-PDH antibodies were noted in subjects with systemic sclerosis, morphea, and
      Raynaud's phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400902
TI  - Hyperprolactinemia inhibits natural killer (NK) cell function in vivo and its
      bromocriptine treatment not only corrects it but makes it more efficient.
AB  - We studied NK cell function in eight patients with pathological
      hyperprolactinemia by measuring 51Cr release by K562 cells exposed to their
      mononuclear cells and found it decreased compared to normal controls (P less than
      0.01). Bromocriptine (BrC) treatment corrected NK function but also made it more
      efficient at 12:1 than at 25:1 or 50:1 effector:target ratios (ANOVA; P = 0.01).
      The study of NK cell function in agarose revealed that its decrease in
      hyperprolactinemia is due to their low active binding to target cells, active
      killing, and recycling capacity. BrC tended to correct them but also increased
      recycling capacity to levels higher than those of controls (P less than 0.05).
      Sequential studies in three hyperprolactinemic patients before and after BrC
      showed correction of NK function within 1 week but its increased efficiency at
      the 12:1 effector:target ratio required 8 weeks. We conclude that
      hyperprolactinemia decreases NK cell function. BrC corrects this by decreasing
      prolactin levels but also makes NK function more efficient by increasing the
      capacity of NK cells to recycle after killing.

PMID- 1400903
TI  - [Quality management in healthcare. Evaluation and improvement].
AB  - Quality in healthcare is a concept ultimately determined by the satisfaction of
      the patient, or more broadly stated, society's needs. Improvement in quality
      begins with the review of health care organizations, in the degree to which their
      current role and function can and do meet these needs. Recent trends in quality
      evaluation have been along the lines of patients satisfaction, as well as
      structure, process, and outcome oriented aspects of health care delivery. Quality
      entails not only the science of medicine itself, but also health care delivery,
      as well as social and individual concerns. In 1990, Japan Hospital Quality
      Assurance Society was founded. The secretariat is located at this department.
      Currently, more than 60 hospitals participate for the development of standards
      and survey to the hospitals. The quality improvement effort has slowly begun to
      put the concept into practice. The public's growing concern is directed toward
      holding healthcare organizations accountable for the services they provide. The
      healthcare field, in turn, is recognizing the needs and merit of voluntary
      commitment to quality, and are placing emphasis on identifying pressing society
      needs, and developing effective leadership. Moving the entire healthcare field in
      the direction of continuous quality improvement will be the key to the survival
      into the 21st century.

PMID- 1400904
TI  - [Partial purification of bone marrow cell-stimulating activity from the
      parenchymal liver cell supernatant].
AB  - Mouse bone marrow cell-stimulating activity has been found in the supernatants of
      mouse parenchymal liver cells. In order to clarify the character, we attempted to
      purify the activity by a four-step purification procedure involving concentration
      and chromatographies on DEAE-cellulose, Sephacryl S-300, and Superose 6. By DEAE
      cellulose chromatography, the activity was found to be eluted stepwisely with 0.1
      M (Peak 1) and 0.2 M (Peak 2) NaCl. Gel filtration revealed that the activities
      in Peak 1 and Peak 2 had molecular weights of 170,000 and 600,000, respectively.
      Both preparations of the activity finally obtained derived the cells which spread
      over the plastic dish from mouse bone marrow cells, but did not stimulate the
      proliferation of IL-3/GM-CSF dependent cell line, IC2. These results suggest the
      presence of the bone marrow cell-stimulating activities, which are different from
      GM-CSF and IL-3, in the parenchymal liver cell supernatants.

PMID- 1400905
TI  - [A roentgenological study of Chilaiditi's syndrome].
AB  - The studies on Chilaiditi's syndrome reported in Japan have been mostly case
      reports on one or two cases. There have been studies on 356 cases in all. We have
      selected 262 cases with detailed data takes from the above 356 cases, together
      with 116 further cases of Chilaiditi's syndrome that we have encountered up to
      1990, i.e. since our previous report in 1965. We also investigated
      roentgenograms, complications, interpositions and age distribution. The syndrome
      was mostly found in middle-aged and elderly patients of 50 years or older. More
      male patients were involved than female, however this is not necessarily true if
      the total number of patients under study is taken into account. Among the
      complications, gastric and duodenal diseases (ulcer and carcinoma) were most
      frequently found, accounting for 20.6% of the total reported cases in Japan. In
      our own study, the percentage was as high as 33.7% because radiography with
      contrast medium was positively conducted on the digestive tract. Of the
      interpositions, the colon accounted for 93.1% of our cases, and 72.9% of the
      total reported cases in Japan. The involved sites were mostly the right hepatic
      flexure of the colon and the transverse colon. From the reports by other
      researchers in the past and our data from 1965, 1975 and 1977, it appears that
      the incidence is about 0.003-0.03%. There were no subjective symptom specific to
      Chlaiditi's syndrome, and there may be various factors accounting for the
      occurrence of the syndrome. The symptoms were primarily based on the underlying
      diseases, and Chilaiditi's syndrome merely indicates the condition where the
      digestive tract interposes between the diaphragm and liver. Therefore, we regard
      this as a radiographical sign rather than a syndrome, and we propose that this
      should be called "Chilaiditi's sign". We also emphasize that the digestive tract
      must be strictly examined if this sign is to be noted.

PMID- 1400906
TI  - [Wave form of intrabronchial spark sound on the chest wall and sound transmission
      in the lung-thoracic system].
AB  - A spark sound was generated in the canine bronchus and sound waves were observed
      on the surface (skin) and on each layer (pectoralis major muscle, intercostal
      muscle and parietal pleura) of the chest wall. The sound wave observed on the
      surface of the chest wall was 5-10 ms in duration, 400-500 Hz in dominant
      frequency and 0.6-1.2 ms in the duration of the initial deflection. Reverse
      dispersion of the waves, i.e., the later components of the wave having longer
      periods, was also recognized. These characteristics of the wave were similar to
      those of time-expanded wave-form of crackle, i.e., discontinuous adventitious
      lung sounds, in clinical cases. Both the spark sound and the sound wave observed
      on the visceral pleura were of short duration, being 0.7 ms and 1 ms,
      respectively. therefore, the main component of the sound wave observed on the
      chest surface was considered to reflect the physical properties of the chest wall
      itself. The analysis of place relationship within the chest wall suggested that
      transmission of the sound across the chest occurred not as a surface wave but as
      a longitudinal wave, therewith traversing the chest wall directly from the sound
      source. The arrival time of the sound was well correlated with the distance
      between the sound source and the positions of the pick-ups on the surface of the
      chest wall. Assuming that the medium between the source and the lung and in the
      chest wall were 71.5 and 29.6 m/sec, respectively. Further studies will be
      necessary to clarify the theory of the sound transmission through the living
      tissue as a viscoelastic body.

PMID- 1400908
TI  - [Utility of SCG (screening colonography) and combined sigmoidoscopy-SCG in
      thorough physical checkups].
AB  - Given the increasing incidence of colon cancer in recent years, it is important
      to establish a diagnostic system for early detection and introduce it into
      clinical practice. A double contrast examination that uses a disposable tip and
      tube with an enema reservoir filled with 200 ml of 60 w/v% barium sulfate, known
      as SCG (screening colonography) was used in this study. In order to assess its
      utility SCG was performed on 1,554 patients, and 2,004 patients were examined by
      a within 24 hours combination of sigmoidoscopy and SCG by way of screening for
      colon cancer. Given the brief duration of SCG, which ranged from 10 to 13 min in
      most patients in the study, the efficiency of the examinations was considered to
      be rather high. Furthermore, the barium reached the cecum in as many as 98.7% of
      the patients. Overall, SCG proved to have an excellent diagnostic capability.
      Sigmoidoscopy-SCG, on the other hand, detected colon cancer in 114 patients
      (5.7%) and colon polyps in 658 patients (32.8%). The rates of detection of colon
      cancers and polyps were higher in the patients who tested positive in
      immunological fecal examinations for occult blood. Judging from our results, it
      may be said that for many patients receiving thorough physical checkups to screen
      for colon cancer, our system will provide for efficient screening whereby
      patients are first examined for fecal occult blood and those who test positive
      undergo sigmoidoscopy and SCG within the same day.

PMID- 1400907
TI  - [Effect of indomethacin on delayed neuronal death of hippocampal CA1 sector in
      gerbil under different levels of controlled cranial temperatures].
AB  - Effect of indomethacin on post-ischemic changes of CA1 neurons was studied in the
      hippocampus of the Mongolian gerbil. The gerbil was employed because due to poor
      development of posterior communicating artery ischemia could be easily induced in
      the forebrain simply by occluding bilateral common carotid arteries. Indomethacin
      (5 mg/kg, i.p.) was administered 30 min before the occlusion. The occlusion
      lasted for 5 divided into four groups. In one group, the temperature was not
      controlled. In the remaining three groups, the temperature was kept at 35.5
      degrees C, 37.5 degrees C, and 39.5 degrees C, respectively. Seven days after the
      occlusion neuronal density was assessed on histological sections stained with
      hematoxylin eosin. It was found that in all groups indomethacin was effective in
      preventing delayed neuronal death regardless of the difference in the cranial
      temperature. However, delayed neuronal death was the least in the lowest
      temperature group. The drug also prevented the post-ischemic hyperthermia
      observed in the temperature non-controlled group. These results indicate that
      indomethacin has its own pharmacological action to prevent delayed neuronal
      death.

PMID- 1400909
TI  - Abundant thyroid hormone is produced by human thyroid cells in culture.

PMID- 1400910
TI  - Neurorehabilitation following right thalamic infarct: effects of cognitive
      retraining on functional performance.
AB  - We treated the cognitive impairments of a 69-year-old male, that persisted 7
      months after an infarction in the distribution of the right posterior cerebral
      artery. The infarct produced a 20% reduction in right cerebral blood flow,
      established by positron emission tomography (PET). Neuropsychological status was
      characterized by marked hemivisuospatial inattention, visuoperceptual and
      perceptuomotor dysfunction, and impaired visual memory. A multiple-baselines
      across behaviors design was utilized to assess effects of specific interventions
      on targeted cognitive functions. We found significant improvement in attention to
      left hemispace in response to directed interventions. Considerable gains were
      also realized in perceptuomotor abilities, mobility, and activities of daily
      living. Results indicated process-specific effects of strategic cognitive
      interventions, initiated 7 months postonset.

PMID- 1400911
TI  - Event-related potentials (ERPs) during repetition priming in Alzheimer's patients
      and young and older controls.
AB  - Although memory tested explicitly (e.g., recognition) is clearly deficient in the
      early stages of Alzheimer's disease, it is less clear if memory tested implicitly
      is similarly affected. To assess this, event-related potentials (ERPs) were
      recorded during a word-repetition priming paradigm, with semantic and
      orthographic orienting tasks, from 10 patients with mild probable Alzheimer's
      disease (PAD; mean age of 70.6), 10 young (24.1) and 10 older (69.8) controls.
      The extent of priming by word repetition was assessed using the new minus old ERP
      repetition effect. The young and older control groups showed clear ERP repetition
      effects that were larger during semantic than orthographic blocks. Although the
      PAD patients displayed the same general trends, their ERP repetition effects were
      not nearly as marked when compared to controls. To the extent that the ERP
      repetition effect recorded during this repetition priming paradigm is a measure
      of implicit performance, the data suggest that memory assessed in this fashion is
      spared in at least some Alzheimer's patients in the early stages of the disease.

PMID- 1400912
TI  - Spatial cognition in Alzheimer's disease: subtypes of global-local impairment.
AB  - This study investigated whether subgroups of AD patients exhibit different
      patterns of impairment in analyzing global (configural) and local (detail)
      features of complex visual stimuli. A High Spatial AD subgroup (i.e., patients
      with better block constructions than naming) and a High Verbal AD subgroup (i.e.,
      patients with better naming than block constructions) were impaired in analyzing
      both global and local forms. As predicted, however, the High Spatial AD patients
      exhibited greater impairment in analyzing the local forms than the High Verbal AD
      patients and normal controls. In contrast, the High Verbal AD patients exhibited
      greater impairment in analyzing the global forms than the High Spatial AD
      patients and normal controls. There was a striking separation of the subgroups:
      Using the local-global difference score, the hit rate for classifying these
      patients into the two subgroups was 91%. Robust correlations were found between
      the AD patients' ability to construct global and local forms and their scores on
      traditional visuospatial and verbal tests, respectively. The findings suggest
      that it may be misleading to subdivide AD patients using a verbal/spatial
      dichotomy, because even those AD patients who appear to have relative strengths
      on traditional visuospatial tests are likely to exhibit a primary impairment in
      analyzing local features of complex visual stimuli. The results underscore the
      importance of a process (qualitative) approach to neuropsychological assessment
      for a more valid understanding of the behavioral subtypes of Alzheimer's disease.

PMID- 1400914
TI  - Inner speech in anarthria: neuropsychological evidence of differential effects of
      cerebral lesions on subvocal articulation.
AB  - The role of articulation in verbal short-term memory was investigated in two
      anarthric patients, C.M. and F.C., both showing normal comprehension for written
      and spoken language, above average intelligence and visuo-spatial abilities.
      Based on experimental results, we propose that subvocal articulation might be
      impaired in anarthric patients in different ways, according to the site of
      lesion: in 'locked-in' patients only the articulatory rehearsal processes
      necessary to enhance memory performances is involved, while in cortical anarthric
      patients the lesion affects the articulatory recoding processes involved in
      transferring visually presented material into an articulatory form for better
      retention.

PMID- 1400913
TI  - Letter matching: effects of age, Alzheimer's disease, and major depression.
AB  - We compared Alzheimer's disease (AD) patients and Major Depressive Disorder
      (MDD), Aged normal, and Young normal controls on a letter-matching task designed
      to measure the time needed to access overlearned linguistic information in long
      term memory. Name identity (NI) and physical identity (PI) reaction time and the
      NI-PI difference were compared for ADs, MDDs, and Aged normals and separately for
      Aged and Young normal groups. AD subjects had slower NI and PI reaction times and
      a bigger NI-PI difference than Aged normal and MDD subjects, suggesting that
      speed of access to overlearned letter-name information in long-term memory is
      slowed for ADs. There were no reliable differences between Aged normal and MDD
      subjects. Aged normals had slower NI and PI reaction times and a bigger NI-PI
      difference than Young normals, suggesting that the highly practiced operations
      needed to access letter-name information slow with age. A discriminant analysis
      was used to evaluate the usefulness of the "easy to perform" letter-matching task
      for diagnostic purposes. Ninety percent of normal and MDD subjects but only 68%
      of AD subjects were classified correctly.

PMID- 1400915
TI  - Cognitive test performances related to early and late computed tomography
      findings after closed-head injury.
AB  - Computed tomography (CT) findings from early (less than 24 hours) and late scan
      (6 months) after closed-head injury (CHI) were compared to cognitive test scores
      obtained on an average of 4 months after injury in a consecutive series of 53
      patients. The presence of parenchymal lesion was associated with poor test
      results, indicating cognitive inflexibility and disinhibition of routine response
      tendencies in novel tasks. These deficits have previously been found to be
      related in particular to frontal-lobe dysfunction, but the present study did not
      support the hypothesis that frontal lesion is the principal cause of this
      impairment in CHI. Parenchymal lesions in the right and left hemisphere were
      associated with spatial and verbal deficits, respectively. Ventricular
      enlargement in the late CT was related to cognitive inefficiency, both being
      strongly associated with age. The results suggest that parenchymal lesion in the
      early CT is an indicator of diffuse axonal injury, which results in cognitive
      inflexibility during recovery.

PMID- 1400916
TI  - Cognitive performance in relatives of patients with probable Alzheimer disease:
      an age at onset effect?
AB  - Cognitive performance of 32 siblings and children of patients with probable
      Alzheimer disease was assessed longitudinally over an interval averaging 4 years.
      Mean scores were within normal limits for age on all measures at both test times.
      However, relatives of patients with early-onset dementia (less than or equal to
      67 years) were more likely to show a decline in performance from the first to
      second testing than relatives of patients with late-onset dementia. Additional
      follow-up will be needed to determine the reliability of performance trajectories
      and to assess whether mild cognitive changes are related to future dementia.
      However, findings suggest that it may be important to consider family history of
      dementia in studies of normal cognitive aging.

PMID- 1400917
TI  - Continuous recognition memory tests: are the assumptions of the theory of signal
      detection met?
AB  - Two continuous recognition memory tests were administered to 20 males and 20
      females using the confidence rating procedure to determine if the underlying
      assumptions of the theory of signal detection (TSD) are met by these tasks. Z
      score transformed ROC curves proved to be straight lines parallel to the positive
      diagonal of the ROC graph. These findings suggest that the distributions of
      familiarity for old and new stimuli are normal and of equal variance for the
      Continuous Recognition Memory and Continuous Visual Memory Tests. TSD
      interpretation of test data appears to be justified.

PMID- 1400918
TI  - CNV evidence for the distinctiveness of frontal and posterior neural processes in
      a traumatic brain-injured population.
AB  - The association between certain behavioral tests of executive functions in humans
      and the integrity of the prefrontal lobes has rested primarily on studies
      comparing subjects with frontal versus other loci of damage. Another approach is
      to compare the within-group variation on a physiological index of frontal
      functioning with the behavioral tests of interest. In the present study, subjects
      with traumatic brain injury (TBI) were given four behavioural measures of
      executive function, two measures of posterior nonexecutive function, and a
      Contingent Negative Variation (CNV) task, a proposed electrophysiological index
      of frontal-lobe functioning. We found that three of the four executive function
      tests were significantly related to the CNV, accounting for 23-52% of the
      variance, while the CNV did not correlate at all with the posterior tasks.

PMID- 1400919
TI  - Longitudinal sensitivity of the Fuld cholinergic profile to Alzheimer's disease.
AB  - The diagnostic sensitivity of a profile (Fuld, 1984) thought to mark cholinergic
      changes in Alzheimer's Disease (AD) was examined in a sample of 53 patients
      meeting criteria for AD on two occasions and in 19 patients for three occasions.
      The low obtained sensitivities of the Fuld profile (17%-26%) across testings is
      consistent with previous studies that used a single time point. The findings also
      revealed unstable positive and negative profiles over time. There were no
      performance differences on intellectual or memory measures when comparing
      subjects identified as positive or negative by the Fuld index. The results
      demonstrate that the index is insensitive to the dementing process and is a poor
      diagnostic marker for AD.

PMID- 1400920
TI  - Individual trajectories of cognitive decline in patients with dementia of the
      Alzheimer type.
AB  - The course of decline was studied in 16 patients with probable or definite
      dementia of the Alzheimer type (DAT) over 2.7 to 6.8 years from first to last
      evaluation. Overall severity of dementia was measured with the Wechsler Adult
      Intelligence Scale (WAIS), the Dementia Rating Scale (DRS), and the Mini-Mental
      State Examination (MMSE), at approximately annual intervals. An initial plateau
      phase, during which language and cognitive functions did not change for periods
      of 9 to 35 months, was observed in 5 patients who initially had an isolated
      memory impairment without significant impairment of nonmemory language or
      visuospatial function. Once nonmemory functions began to decline, the rate of
      decline was remarkably steady in most individual patients but varied markedly
      among patients. The initial rate of decline after the plateau phase, as measured
      with the WAIS and DRS, was a significant predictor of subsequent rate in
      individual patients (r = .66, p less than .01, and r = .67, p less than .01, for
      the WAIS and DRS, respectively). The MMSE was a less reliable measure of
      longitudinal change in dementia severity and did not predict future rates of
      decline (r = .29). These results demonstrate a biphasic trajectory of decline in
      patients with DAT. Stable interindividual differences in rate of decline may
      provide a basis for designing more sensitive studies of treatments intended to
      slow or halt the progress of DAT.

PMID- 1400921
TI  - Verbal and nonverbal skill discrepancies in hydrocephalic children.
AB  - This study evaluated a large sample (N = 90) of 5- to 7-year-old children with
      hydrocephalus caused by aqueductal stenosis or prematurity-intraventricular
      hemorrhage or associated with spina bifida. Comparison groups of normal controls,
      children with spina bifida and no shunt, and premature children with no
      hydrocephalus were also evaluated. Comparison of skill discrepancies at two
      occasions separated by 1 year revealed that hydrocephalic children, as a group,
      showed poorer nonverbal than verbal skills on measures from the McCarthy Scales
      of Children's Abilities, the WISC-R, and composites of neuropsychological skills.
      No discrepancies in verbal-nonverbal memory were found nor were any discrepancies
      attributable to etiology or motor demands of the tasks. Consistent with current
      hypotheses concerning the role of the cerebral white matter in cognitive
      development, these results show that hydrocephalic children in this age range
      generally have poorer development of nonverbal cognitive skills relative to their
      language development.

PMID- 1400922
TI  - A five-factor model for motor, psychomotor, and visual-spatial tests used in the
      neuropsychological assessment of children.
AB  - Previous confirmatory factor analysis has supported a distinction between simple
      and complex motor skill tests in a modified and expanded Halstead Reitan test
      battery (HRB). The present study used a sample of 722 right-handed boys and
      girls, aged 9 through 12, and expanded the sample of motor, psychomotor, and
      visual-spatial tests to further clarify this distinction. Restricted maximum
      likelihood factor analysis resulted in correlated factors of Simple Motor Skill,
      Complex Visual-Spatial Relations, Simple Spatial Motor Operations, Motor
      Steadiness, and Speeded Motor Sequencing. These results provide additional
      evidence for the discriminant validity of this particular battery of tests, and
      explicate further the skills and abilities measured in neuropsychological
      assessments of children referred for evaluation.

PMID- 1400923
TI  - Learning disability subtyping: a reply to Adams.

PMID- 1400924
TI  - Dichotic listening in aphasics: response to Niccum and Speaks.
AB  - Since the dichotic listening technique was first described (Broadbent, 1954;
      Kimura, 1961), researchers have been interested in its ability to document
      hemispheric dominance for language and other functions in a noninvasive fashion.
      Numerous articles have been published using normal healthy subjects as well as
      others using patients who have suffered neurological disease or damage. Much
      controversy has been generated over the use of dichotic listening in the latter
      population, however, since unilateral brain lesions might be expected to alter
      normal perception. This paper responds to one recently published by Niccum and
      Speaks (1991) that attempted to explain why a lesion effect, and not hemispheric
      reorganization, is the best explanation for findings of left-ear advantage in
      recovering aphasics.

PMID- 1400925
TI  - 'Test-tube' primates: the next generation.

PMID- 1400926
TI  - Serum placental protein 14 (PP14) reflects endometrial status during hormone
      replacement therapy.
AB  - Healthy post-menopausal women were randomly assigned to treatment groups
      receiving 28 day treatment cycles of oestradiol valerate (2 mg, days 1-28)
      sequentially combined with levonorgestrel (75 micrograms, days 17-28) (n = 19);
      oestradiol valerate (2 mg, days 1-28) continuously combined with cyproterone
      acetate (1 mg, days 1-28) (n = 18), or placebo (n = 22). Treatment continued for
      2 years. After therapy, the women receiving the sequential combination had an
      early secretory phase (74%) or atrophic endometrium (26%). All women receiving
      the continuous combination or placebo had inactive or atrophic endometrium, or
      the tissue was inadequate for assessment. Biochemical parameters of endometrial
      secretion [oestradiol dehydrogenase (EDH), isocitrate dehydrogenase (ICDH)]
      measured in endometrial tissue and placental protein (PP14) measured in serum
      were all low in the groups receiving the continuous combination and placebo.
      During sequential treatment, all biochemical parameters showed significantly
      higher mean values. Serum PP14 accurately reflected this pattern. Furthermore, in
      the sequentially treated group, serum PP14 correlated highly significantly with
      EDH (r = 0.70; P less than 0.001) and ICDH (r = 0.57; P = 0.01). These
      correlations were of the same magnitude as the correlations between the
      endometrial markers, which indicates that serum PP14 reflects the endometrial
      status. Furthermore, serum PP14 measurements at 3 months and at 2 years of
      treatment were highly correlated, reflecting the long-term validity of the
      measurement. The present data suggest that PP14 measured in serum may be used to
      assess endometrial status. Further studies are required to determine whether
      serum PP14 will discriminate pathological endometrial conditions.

PMID- 1400927
TI  - Effect of RU 486 on the endometrial response to deciduogenic stimulus in
      ovariectomized rhesus monkeys treated with oestrogen and progesterone.
AB  - Using the artificial plaque--decidual cell model in rhesus monkeys, the potential
      role of progesterone in the process of of epithelial and stromal cell responses
      was investigated by time-adjusted application of an antiprogestin, RU 486.
      Epithelial plaque formation is an immediate response of the endometrium to either
      trauma or invading trophoblast cells. To study this process, RU 486 (2.5 mg/kg
      body weight) or vehicle (ethanol/saline, 7:3, v/v, i.m.) was administered to the
      first group of monkeys immediately following traumatization (days 16 and 17 of
      treatment cycle). Histometric analysis revealed that treatment with RU 486 led to
      significant inhibition (P less than 0.001) in the recruitment of epithelial cells
      into plaque acini and consequent reduction (P less than 0.001) in the spread of
      the plaque reaction compared with control monkeys. In the second group of
      monkeys, experimental treatment was delayed until plaque formation had occurred
      (days 21 and 22 of cycle). RU 486 induced increased degeneration (P less than
      0.01) in plaque cells. Thus the transformation and the maintenance of the
      epithelial plaque response appears to be progesterone-dependent. Glandular
      epithelium showed only marginal changes (P less than 0.05) in maximum cell
      height, amount of pseudostratification and secretory activity of glands as a
      consequence of RU 486 treatment; however, the antiprogestin induced a higher
      incidence of glandular apoptosis (P less than 0.01 for both groups). It has been
      suggested that the higher degree of apoptosis in the glandular epithelium could
      be a consequence of the progesterone receptor blocking action of RU 486. No
      distinctive change in endothelial cell ultrastructure was evident following RU
      486 treatment; however, venular diameter was significantly increased (P less than
      0.01, group I; P less than 0.001, group II) along with an apparent reduction in
      the extent of oedema. There was increased extravasation (P less than 0.01) and
      leukocytic infiltration (P less than 0.001, group I; P less than 0.05, group II)
      following RU 486 treatment. RU 486 induced vascular responses and increased
      diapedesis could presumably have resulted from its progesterone blocking action
      in vascular cells. RU 486 accelerated the incidence (P less than 0.01) of stromal
      decidualization (group I), as well as quantitatively accentuating (P less than
      0.001) the decidual cell reaction (group II). It is possible that RU 486 may
      inhibit specific functions of decidual cells, despite morphologically consistent
      decidual transformation.

PMID- 1400928
TI  - Pure human follicle stimulating hormone has a role in the treatment of severe
      male infertility by assisted reproduction: Norfolk's total experience.
AB  - Fifty patients [79 in-vitro fertilization (IVF) cycles] with severe male factor
      infertility were included in an experimental clinical trial running from October
      1987 to March 1991 to assess the potential of systemic follicle stimulating
      hormone (FSH) treatment to improve sperm fertilizing ability in IVF. Two groups
      were defined: a secondary group (24 patients, 33 IVF cycles) with a history of
      failed fertilization in previous IVF attempts and a primary group (26 patients,
      46 IVF cycles) with poor sperm parameters which suggested that fertilization
      would not occur according to previously established criteria. Basic semen
      analysis and a battery of endocrine radioimmunoassays [serum FSH, luteinizing
      hormone (LH), oestradiol, prolactin and testosterone] were performed in these
      patients. Bioactive-FSH and LH were also determined in some patients. For this
      study, pure FSH was administered (150 IU i.m. three times per week) for at least
      3 months, after which the semen analysis and endocrine tests were repeated.
      Although no significant changes were observed after FSH therapy, either in the
      endocrine profile or in the basic semen parameters, except for FSH
      radioimmunoassay levels, the fertilization rate of pre-ovulatory oocytes was
      significantly improved from 2 to 54.4% in the secondary group; the primary group
      showed a 52.3% fertilization rate. Eighteen clinical pregnancies were achieved,
      11 in the primary group and seven in the secondary group, giving 30 and 26% term
      pregnancy rates per transfer respectively. These results, which are in complete
      agreement with our preliminary study, re-emphasized the benefits of systemic FSH
      administration as an adjunct to assisted reproduction in selected cases of severe
      male factor infertility.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400929
TI  - Effect of the ratio of follicle-stimulating hormone to luteinizing hormone on rat
      granulosa cell proliferation and oestradiol-17 beta secretion.
AB  - The present study examined the effects of the ratio of follicle-stimulating
      hormone (FSH) to luteinizing hormone (LH) on granulosa cell proliferation and
      oestradiol-17 beta secretion. For these studies, ovarian segments from either
      immature rats or those primed with pregnant mares serum gonadotrophin (PMSG) were
      incubated for 5 h with [3H]thymidine and FSH (0-100 mIU/ml) with or without
      equivalent doses of LH. After incubation, granulosa cells were isolated and their
      mitotic activity estimated by determining the amount of [3H]thymidine
      incorporated into the DNA. The amount of oestradiol secreted into the media was
      measured by radioimmunoassay. Compared to granulosa cells from immature ovaries,
      granulosa cells from PMSG-primed ovaries required significantly less FSH to
      stimulate incorporation of [3H]thymidine, had a 9-fold higher basal level of
      oestradiol production and increased oestradiol secretion in response to
      gonadotrophins. At pharmacological serum levels (10-20 mIU of total
      gonadotrophin), FSH:LH ratios of less than or equal to 2 increased oestradiol
      secretion from PMSG-primed ovaries but did not increase the rate of [3H]thymidine
      incorporation. Conversely, FSH:LH ratios of greater than or equal to 3 stimulated
      [3H]thymidine incorporation without altering oestradiol secretion. These data
      demonstrate that granulosa cells of immature follicles not secreting oestradiol
      are relatively unresponsive to gonadotrophins at any dose tested. Once the
      capacity for oestradiol secretion develops, then both the dose and ratio of FSH
      and LH play major roles in determining whether the follicle will grow or secrete
      oestradiol.

PMID- 1400930
TI  - Effects of short-term GnRH agonist--human menopausal gonadotrophin stimulation in
      patients pre-treated with progestogen.
AB  - The recent use of gonadotrophin-releasing hormone agonist in a short-term regimen
      has allowed the effectiveness of human menopausal gonadotrophin (HMG) stimulation
      to be markedly improved. It seems to be related to the flare-up effect of the
      agonist in the early follicular phase of the cycle. However, individual hormonal
      responses to the agonist are quite variable and four patterns of oestradiol
      secretion have been described. The present study indicates that in women pre
      treated with progestogen, only two patterns of serum oestradiol are observed in
      the flare-up period, with a significant increase in 57% of patients. Significant
      correlations are observed between oestradiol values and the endogenous
      gonadotrophin surge (positively with luteinizing hormone, r = 0.38; P less than
      0.05 and negatively with follicle stimulating hormone, r = 0.48; P less than
      0.005). Furthermore, there was a significant relationship between the hormonal
      flare-up and the ovarian parameters following HMG stimulation. In conclusion, in
      progestogen-pre-treated women, the serum oestradiol level during the flare-up
      period is a reliable index to predict subsequent effectiveness of ovarian
      stimulation with HMG.

PMID- 1400931
TI  - Polycystic ovary syndrome: low-dose follicle stimulating hormone administration
      is a safe stimulation regimen even in previous hyper-responsive patients.
AB  - We studied 23 women with polycystic ovarian syndrome (PCOS), resistant to
      clomiphene citrate, who had a previous history of multifollicular ovarian
      development on gonadotrophin stimulation. Each woman had one cycle of
      gonadotrophin-stimulating hormone agonist/human menopausal gonadotrophin
      (GnRHa/HMG) stimulation and then one cycle of low-dose follicle stimulating
      hormone (FSH) stimulation. All GnRHa/HMG cycles were multifollicular. On the low
      dose FSH protocol, 10 cycles were unifollicular, while two to three follicles
      were observed in nine cycles, and four cycles were multifollicular. The ovarian
      hyperstimulation syndrome ensued in one of the FSH cycles versus 13 of the
      GnRHa/HMG cycles. Despite decreasing luteinizing hormone (LH) levels and
      increasing FSH levels, androgen levels increased during stimulation on both
      protocols. There was one pregnancy in the GnRHa/HMG cycles versus six pregnancies
      following the FSH cycles. In conclusion, low-dose FSH administration seems a safe
      stimulation regimen with a satisfactory conception rate even in PCOS women with a
      previous record of multifollicular ovarian development.

PMID- 1400932
TI  - Is continuation of a gonadotrophin-releasing hormone agonist (GnRHa) necessary
      for women at risk of developing the ovarian hyperstimulation syndrome?
AB  - A total of 28 women scheduled for in-vitro fertilization used buserelin and human
      menopausal gonadotrophin (HMG) for ovarian stimulation. One group (I) of 17 women
      was given human chorionic gonadotrophin (HCG 10,000 IU) to trigger ovulation, but
      the resulting embryos were electively cryopreserved because of the risk (serum
      oestradiol greater than or equal to 3500 pg/ml) of developing the ovarian
      hyperstimulation syndrome (OHSS). Six women continued the buserelin therapy in
      the luteal phase and eleven did not. In group II (n = 11), the HMG injections
      were discontinued because of an exaggerated ovarian response and the HCG was
      omitted. Six of these women continued the buserelin injections until the onset of
      menses and five did not. In both groups, the ovarian response to induction of
      ovulation (serum oestradiol concentrations and number of follicles) was similar
      for those who did or did not continue buserelin therapy. There was no difference
      in the rate of ovarian quiescence (weekly fall in serum oestradiol concentration
      following the stimulation) between those women who did or did not continue the
      buserelin therapy in either group. The serum luteinizing hormone concentrations
      remained low in all women in both groups. We conclude that the omission of
      buserelin therapy after discontinuing the HMG in women at risk of developing OHSS
      does not affect subsequent ovarian quiescence.

PMID- 1400933
TI  - The effect of gonadotrophin-releasing hormone (GnRH) agonist in the follicular
      phase on in-vitro fertilization outcome in normo-ovulatory women.
AB  - Sixty-three normo-ovulatory infertile women were randomly divided into two
      groups. All women were first desensitized with the gonadotrophin-releasing
      hormone agonist (GnRHa), buserelin. Thereafter, ovarian stimulation with human
      menopausal gonadotrophins (HMG) was started in both groups but in group A the
      GnRHa was stopped on the same day. In group B, the GnRHa was continued during HMG
      treatment until the ovulatory human chorionic gonadotrophin stimulus was given.
      Premature luteinization was not observed in either group, although the
      preovulatory basal luteinizing hormone (LH) secretion was significantly higher in
      group A. An equal number of embryos of comparable quality was transferred in both
      groups and the pregnancy outcome was similar. However, the supernumerary embryos
      of group A were of a lower morphological quality and survived the
      cryopreservation process less well. We concluded that the continuous
      administration of a GnRH agonist during HMG treatment resulted in better quality
      of supernumerary embryos.

PMID- 1400934
TI  - The role of oocyte donation in women who are unsuccessful with in-vitro
      fertilization treatment.
AB  - Oocyte donation improves the chances of becoming pregnant in some women who are
      unsuccessful with in-vitro fertilization (IVF) treatment. A total of 119 IVF
      cycles achieved a pregnancy rate per cycle of 2.5% whereas the same women, when
      treated with 45 cycles of oocyte donation, achieved a 24.5% pregnancy rate per
      cycle. To ascertain which women may be helped by oocyte donation, IVF data were
      analysed according to the outcome of oocyte donation. There was a difference in
      the number of previous natural conceptions and live births, and in the IVF
      fertilization rate. There was no difference in the age of the women and the
      numbers of oocytes collected per cycle of IVF. New criteria are therefore
      suggested for recommending oocyte donation to women who have previously failed to
      become pregnant with IVF treatment.

PMID- 1400935
TI  - Oocyte and embryo donation: evaluation of 412 consecutive trials.
AB  - A total of 199 patients (412 consecutive cycles) were treated by oocyte-embryo
      donation in 336 replacement cycles. Of these, 296 involved intra-uterine embryo
      transfers, 38 zygote intra-Fallopian transfers (ZIFT) and two gamete intra
      Fallopian transfers (GIFT). Of the 336 replacements, 244 (73%) constituted
      transfers of fresh concepti and 92 (27%) of frozen-thawed ones. A total of 85
      pregnancies were achieved of which 16 ended in preclinical abortions, giving a
      clinical pregnancy rate of 34.7% per patient, 20.5% per transfer and a take-home
      baby rate of 29.1% per patient. The pregnancy rate was significantly higher (P
      less than 0.05) following fresh gamete or embryo replacement (23%; 56/244) than
      following that of frozen-thawed embryos (14.1%; 13/92). No significant difference
      was observed when intra-Fallopian replacement was applied (27.5%; 11/40) as
      opposed to intra-uterine (19.6%; 58/296). Ovarian function was not found to be of
      significant importance to the achievement of pregnancies after oocyte donation
      since comparable pregnancy rates per replacement and per started cycle were
      obtained in patients with ovarian failure and in those with functional ovaries
      (19% and 15.4%; 24.2% and 20.2% respectively). Comparison of the implantation and
      abortion rates between these two groups did not reveal any significant difference
      (11.1% and 11.1% versus 14.8% and 16.6%). The highest pregnancy rate among
      patients with ovarian failure was observed in those with primary ovarian failure
      (26.4%; 14/53), while the lowest was among women who had received chemotherapy
      and/or radiotherapy (9%; 1/11).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400936
TI  - Clinical and meiotic studies in an infertile man with Y;13 translocation.
AB  - Clinical and meiotic studies were done on an infertile man with a translocation
      between Yq and 13q, who was identified through the birth of his son with partial
      trisomy 13q. Seminal plasma transferrin showed preserved Sertoli cell function
      while lactate dehydrogenase C4 indicated hypospermatogenesis. A quadrivalent in
      diakinesis and spermatogenic arrest in the second meiotic division was detected.

PMID- 1400937
TI  - In-vitro fertilization in cases with severe sperm defect: use of a swim-across
      technique and medium supplemented with follicular fluid.
AB  - The purpose of this study was to evaluate a new method of in-vitro fertilization
      (IVF) in patients with severe sperm defects. Unlike the conventional swim-up
      method, spermatozoa and oocytes are placed in opposite corners of the bottom of
      the incubation dish so that sperm swimming is horizontal instead of vertical.
      Another difference between the swim-across and swim-up techniques is that the
      incubation medium is supplemented with 20% follicular fluid. After a randomized
      series (protocol I) of 15 IVF attempts had demonstrated that swim-across was more
      effective than swim-up in terms of fertilization and cleavage, we began a second
      series (protocol II) using only swim-across. A total of 124 couples with motile
      sperm counts less than 1 x 10(6) spermatozoa/ml of semen were included in
      protocol II. Clinical parameters (age, tubal damage) and number of recovered
      oocytes were recorded and compared in patients who did (group A: n = 94) and did
      not (group B: n = 74) achieve fertilization. In group A the fertilization rate
      was 36.7% and, out of the 94 transfers that were made, there were 21 clinical
      pregnancies and 12 full-term pregnancies with 16 live births. The number of
      oocytes collected (12 versus 7.7, P less than 0.001) and the incidence of tubal
      damage (50% versus 24.3%, P less than 0.001) was significantly higher in group A
      than in group B. Using logistic regression analysis, we showed a significant
      correlation between fertilization and progressive motility, percentage normal
      spermatozoa, number of recovered oocytes and tubal damage.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1400938
TI  - Male factor as determinant of in-vitro fertilization outcome.
AB  - The effect of different semen parameters was evaluated in 200 consecutive couples
      in an in-vitro fertilization (IVF) programme. All semen analyses were performed
      on the native aliquot of semen which was subsequently prepared and used for in
      vitro insemination. Morphology evaluation using strict criteria (kappa 0.46 and r
      = 0.565) was compared with progressive motile sperm density (kappa 0.37 and r =
      0.333) and the conventional World Health Organisation (WHO) evaluation of
      morphology (kappa 0.31 and r = 0.378). Results show that morphology evaluation
      using strict criteria is the best predictor of IVF and density of progressively
      motile spermatozoa can be an optional method. The combined results of strict
      morphology and motile concentration progressively showed that if both parameters
      were below the cut-off points of 5% and 3 x 10(6)/ml respectively, the
      fertilization rate per oocyte was very low (18%). No pregnancies were achieved in
      this group. When both parameters were above the cut-off points, the fertilization
      rate per oocyte was high (72%) (P less than 0.005) and the pregnancy rate per
      embryo transfer was 27%. Predictive values indicate that morphology evaluation
      using strict criteria and the number of progressive motile spermatozoa can be
      used as patient selection criteria for infertility clinics.

PMID- 1400939
TI  - Laparoscopic application of interceed (TC7).
AB  - Interceed (TC7) is a surgical adjuvant which has been shown to be efficacious in
      reducing adhesion formation in gynaecological pelvic surgery by laparotomy. In
      view of the increasing number of laparoscopic interventions and the concern with
      reducing post-operative adhesions, we evaluated the possibility of Interceed
      delivery through the ancillary trocars. Twenty-four patients underwent operative
      laparoscopy followed by the application of Interceed. No difficulties were
      noticed. Material sized from 1.9 x 2.5 to 3.8 x 5 cm was successfully delivered
      into the peritoneal cavity, while the duration of the procedure ranged from 2.5
      to 6 min for each piece. In conclusion, it is feasible to consider application of
      Interceed during laparoscopic interventions. This approach to delivery requires a
      short operative time, minimal instrumentation and enhanced ease of application.

PMID- 1400940
TI  - Improved development of human embryos in vitro by a human oviductal cell co
      culture system.
AB  - This study was undertaken to determine the effect of co-culture with human
      oviductal cells on human embryos. Spare embryos from gamete intra-Fallopian
      transfer (GIFT), pronuclear stage transfer (PROST) and in-vitro
      fertilization/embryo transfer (IVF/ET) programmes were either cultured in serum
      supplemented Earle's balanced salt solution alone, or co-cultured in the same
      solution with oviductal cells from the pronuclear stage (day 1 post-insemination)
      or two- to four-cell stage (day 2 post-insemination). The co-cultured embryos
      appeared to have a higher developmental potential (higher rate of blastocyst
      formation and lower fragmentation rate), although there was no statistical
      difference in their rate of development, degree of fragmentation and stages
      attained, when compared with conventionally cultured embryos. The percentage of
      hatching blastocysts was significantly higher (P less than 0.05, Fisher's exact
      test) for embryos co-cultured from day 1 post-insemination (38%) than for embryos
      which had not been co-cultured (7%). The blastocyst hatching rate for embryos co
      cultured from day 2 post-insemination was 15%. It was therefore concluded that co
      culture of human embryos with oviductal cells could improve the development of
      the embryos in vitro. The degree of improvement was more pronounced when the co
      culture started at an earlier stage.

PMID- 1400941
TI  - The influence of solubilized porcine zona pellucida protein on the binding
      capacity of human spermatozoa.
AB  - The acrosome reaction, sperm-zona pellucida binding, sperm-oolemma binding/fusion
      and subsequent fertilization are known to be influenced by homologous as well as
      heterologous follicular fluid and zona pellucida protein. In this study, the
      effect was investigated of different concentrations of solubilized porcine zona
      pellucida protein on the zona binding potential of human spermatozoa under
      hemizona assay conditions. Human spermatozoa incubated with 617 and 142
      micrograms/ml porcine zona pellucida protein showed a statistically significant
      increase in zona binding when compared with control spermatozoa (106.5 +/- 18.0
      versus 60.9 +/- 29.0, P less than 0.02 and 111.0 +/- 26.6 versus 63.0 +/- 25.5, P
      less than 0.0001, respectively). Concentrations of 67 micrograms/ml porcine zona
      pellucida protein did not show a significant increase in zona binding (78.7 +/-
      21.7 versus 66.7 +/- 25.4, P greater than 0.05). Control zona binding values for
      different experiments did not differ significantly (60.9 +/- 29.0; 63.0 +/- 25.5;
      and 66.7 +/- 25.4, P greater than 0.6). In conclusion, it seems likely that a
      factor(s) present in the porcine zona pellucida might play a beneficial role
      during human sperm-oocyte binding. The results of the study might be used in
      future investigations to manipulate gamete interaction to such an extent that
      improved fertilization rates can be accomplished.

PMID- 1400942
TI  - Increased pregnancy failure rates after clomiphene following assisted
      reproductive technology.
AB  - The obstetric outcome of 1941 in-vitro fertilization (IVF) and 1436 gamete intra
      Fallopian transfer (GIFT) pregnancies reported from 25 units in Australia and New
      Zealand have been reviewed. Recently, gonadotrophin-releasing hormone analogues
      (GnRHa) have replaced clomiphene as part of many ovarian stimulation protocols.
      Clinical abortion rates after clomiphene (24.4% for IVF; 23.0% for GIFT) were not
      significantly higher than after GnRHa (20.7% for IVF; 17.9% for GIFT) when IVF
      and GIFT data were considered separately. However, the abortion rate for combined
      IVF and GIFT was significantly higher after clomiphene than after GnRHa. This
      pattern was found for most maternal age groups and causes of infertility although
      differences were not significant in all categories. The combined IVF and GIFT
      ectopic pregnancy rate of 6.7% for clomiphene was significantly higher than 4.1%
      for GnRHa. Because the mechanism of action of clomiphene for oocyte recruitment
      during folliculogenesis means that GnRHa cannot be used with clomiphene,
      luteinizing hormone (LH) levels are higher in clomiphene cycles than in GnRHa
      cycles. Clomiphene itself could cause the increase in pregnancy wastage or
      increased levels of LH during follicule genesis associated with the use of
      clomiphene may cause the observed pregnancy failures.

PMID- 1400943
TI  - Births in Israel resulting from in-vitro fertilization/embryo transfer, 1982
      1989: National Registry of the Israeli Association for Fertility Research.
AB  - Our objective was to describe the characteristics of pregnancies, deliveries and
      children at birth following in-vitro fertilization (IVF) and related technologies
      in Israel, from 1982 to 1989. A national survey with collaboration from all IVF
      units in the public hospitals was designed and data were collected on individual
      patients. Comparison of results was made with data from a national delivery
      census and from other national IVF registries. During the period covering this
      survey, 1149 deliveries resulted in 1475 newborns; 98% of deliveries occurred
      following conventional IVF and embryo transfer (IVF-ET), 2% after in-vivo
      fertilization and gamete intra-Fallopian transfer. Following IVF-ET, 23% of the
      pregnant women were hospitalized due to a complication of pregnancy and 47.3% of
      the deliveries were by Caesarean section (41% if multiple births are omitted).
      The male to female birth ratio was 1.07:1.0; 23.6% of the deliveries were
      multiple births, 28.6% of deliveries were pre-term and the median length of
      gestation decreased with multiple births. At delivery, 23.8% of newborns weighed
      less than 2500 g. The incidence of low birthweight newborns was significantly
      higher in multiple births. The ratio of perinatal mortality (22.8/1000), double
      the incidence found in a national census (13/1000), increased dramatically with
      multiple births (12.7, 24.5 and 75.8/1000 for singleton, twins and triplets
      respectively). The incidence of a major congenital malformation was 2.2%, no
      higher than in the general population. A survey of published national IVF
      registries from Australia and New Zealand, Great Britain, USA and France showed
      much similarity in all aspects of pregnancy outcome following IVF and related
      technologies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1400944
TI  - Successful treatment with methotrexate of five vital interstitial pregnancies.
AB  - Five patients with vital, unruptured interstitial pregnancies of less than 3 cm
      maximum diameter were treated successfully with methotrexate and leucovorin
      rescue. Four pregnancies showed cardiac activity. Diagnosis was established with
      transvaginal ultrasonography in all patients. The human chorionic gonadotrophin
      serum levels were measured to monitor the effectiveness of therapy. This is the
      first publication on methotrexate treatment for interstitial twin pregnancy and
      the first on instillation of methotrexate after puncture and aspiration of
      interstitial pregnancy. In all cases, total and uneventful regression of
      trophoblast tissue was achieved. No adverse reactions were observed. The
      advantages and drawbacks of these therapeutic approaches are discussed.
      Methotrexate appears to be an effective medical non-surgical treatment for
      unruptured interstitial pregnancy with or without cardiac activity, and preserves
      reproductive potential.

PMID- 1400945
TI  - Incidence and significance of unequal gestational sac diameter or embryo crown
      rump length in twin pregnancy.
AB  - The incidence of differences in gestational sac diameter and crown-rump length,
      measured at the time of the first ultrasound, in which at least one gestational
      sac or crown-rump length could be visualized, were analysed retrospectively in
      260 twin pregnancies in which one or both fetuses were delivered at term. The
      difference in gestational sac diameter averaged 1.2 +/- 0.1 mm for pregnancies
      which ended in twin births, compared to 2.0 +/- 0.3 mm when pregnancy ended in
      single births (P less than 0.02). The difference in crown-rump length averaged
      2.4 +/- 0.6 mm for pregnancies which ended in a single birth, compared to 0.9 +/-
      0.1 mm for twin births (P = 0.02). Disparities of greater than or equal to 3 mm
      in gestational sac diameter (P less than 0.05) or crown-rump length (P less than
      0.001) were associated with an embryo loss rate greater than or equal to 50%. The
      disparity in gestational sac diameter (P less than 0.04) and crown-rump length (P
      less than 0.01) was smaller in pregnancies resulting from assisted reproductive
      technologies, compared with pregnancies resulting from coitus or insemination.
      Differences in gestational sac diameter and crown-rump length in early pregnancy
      were unrelated to differences in birth weight, length or sex.

PMID- 1400946
TI  - Embryo reduction in multifetal pregnancies using saline injection: comparison
      between the transvaginal and the transabdominal approach.
AB  - A total of 30 patients with multifetal pregnancies, all resulting from treatment
      with superovulatory agents or assisted reproductive techniques, underwent embryo
      reduction. All patients had three or more fetuses (one sextuplet, two
      quintuplets, seven quadruplets and 20 triplets). The procedure was carried out
      using intra-embryonal injection of 0.9% sodium chloride solution. Embryo
      reduction was carried out via the transabdominal approach in 10 patients,
      performed at 11-12 weeks of gestation, and via the transvaginal route in 20 other
      patients, at 8-10 weeks of gestation. In the transabdominal group, one patient
      aborted following repeated attempts at embryo reduction while the other nine gave
      birth to healthy newborns (eight twins and one triplet). In the transvaginal
      group, four pregnancies are currently ongoing (all beyond 28 weeks of gestation),
      14 pregnancies resulted in a delivery of at least one live newborn (13 twins and
      one singleton), one patient had a late abortion at 24 weeks' gestation and
      another was delivered at 27 weeks' gestation due to severe pre-eclampsia.
      Transvaginal ultrasound-guided needle procedures are commonly practised in most
      in-vitro fertilization units. The employment of this route for embryo reduction,
      performed at an earlier gestational age and with the use of a non-toxic substance
      such as 0.9% saline solution, is advocated.

PMID- 1400947
TI  - Prophylaxis of ovarian hyperstimulation syndrome.

PMID- 1400948
TI  - Role of varicocele in male infertility.

PMID- 1400949
TI  - New vancomycin disk diffusion breakpoints for enterococci. The National Committee
      for Clinical Laboratory Standards Working Group on Enterococci.
AB  - Since 1988, when the first vancomycin-resistant enterococcus was described,
      several descriptions of failures of disk diffusion breakpoints to detect low
      level vancomycin resistance (MICs, 8 to 32 micrograms/ml) have been published. A
      four-laboratory collaborative study was undertaken to establish more accurate
      breakpoints for the disk test. Mueller-Hinton agar was used to perform dilution
      testing (in three laboratories) and disk diffusion testing (in all laboratories).
      Results were determined at 18, 24, and 48 h, and zones of inhibition were read
      using both transmitted and reflected light. One hundred organisms (35
      Enterococcus faecalis, 55 E. faecium, and 10 E. gallinarum or E. casseliflavus
      isolates) were selected to represent vancomycin-susceptible and -resistant
      phenotypes. Interlaboratory agreement of agar dilution MICs was better at 24 h
      (91 to 94% within +/- 1 dilution) than at 18 h (76% within +/- 1 dilution).
      Therefore, 24-h agar dilution MIC results were used as the reference. For disk
      diffusion, it was critical to note the presence of a haze or colonies inside the
      zone when interpreting the test, since this correlated better with the results of
      the agar dilution test. The presence of a haze or inner colonies was best
      detected by reading the zones with transmitted light and incubating the plates
      for a full 24 h. When plotted against 24-h agar dilution MICs, breakpoints of </=
      14 mm (resistant), 15 to 16 mm (intermediate), and >/= 17 mm (susceptible)
      resulted in 58 minor errors (14.5% of total values) and 5 very major errors (2.2%
      of resistant values or 1.3% of total values). No major errors were seen. Results
      of repeat testing using a common lot of Mueller-Hinton agar showed 52 minor
      errors (13.3%) and 4 major errors (4.2% of susceptible values of 1.0% pf total
      values) but no very major errors. It is recommended that any haze or colonies
      within the zone be taken into account when determining zones of inhibition and
      that an MIC test be performed for strains with intermediate zones if vancomycin
      is being considered for treatment.

PMID- 1400950
TI  - Relationship between frequency of infectious human immunodeficiency virus type 1
      harboring cells and kinetics of viral replication: a simple procedure for
      quantitation of infectious virus-carrying cells in blood samples.
AB  - Statistical analysis of a limiting dilution assay (LDA) showed that the
      occurrence of infectious human immunodeficiency virus type 1 (HIV-1)-harboring
      cells in serially diluted samples of peripheral blood mononuclear cells (PBMCs)
      of HIV-1-seropositive patients fits the model describing a single-hit Poisson
      distribution. This observation led to the discovery that there is a direct
      correlation (r = 0.957) between the number of HIV-1-positive cells and the time
      when viral culture produces 1 ng of the HIV-1 p24 gag protein per ml. Frequency
      estimates based on this relationship were highly accurate (P less than 0.01)
      within the first 15 days of viral culture, which consisted of coculture of 10(6)
      normal PBMCs with the equivalent number of test PBMCs. This approach was less
      cumbersome than LDA and was sensitive enough to detect a single infectious HIV-1
      harboring cell among as many as 320,000 cells. The values obtained for 57
      patients agreed well with the data in the literature and showed that the
      frequencies of infectious cells in PBMCs reflect the advancement in the clinical
      stage, being 1/38,000, 1/11,000, and 1/7,000 for asymptomatic patients (Centers
      for Disease Control [CDC] group II/III), patients with AIDS-related complex (CDC
      group IVa), and patients with AIDS (CDC group IVb/c), respectively. A nearly 10
      fold disparity in mean frequencies was observed when these values were correlated
      with the numbers of CD4-positive cells (1/9,000, 1/1,500, and 1/300,
      respectively, for asymptomatic patients, patients with AIDS-related complex, and
      patients with AIDS). The described method provides a simple means of determining
      infectious HIV-1-positive cells in blood samples.

PMID- 1400951
TI  - Evaluation of a monoclonal antibody-based latex agglutination test for diagnosis
      of cryptococcosis: comparison with two tests using polyclonal antibodies.
AB  - Cryptococcal antigen detection has become a routine biological test performed for
      patients with AIDS. The poor prognosis of cryptococcosis explains the need for
      reliable tests. We evaluated the performances of a newly commercialized
      agglutination test that uses a monoclonal antibody specific for cryptococcal
      capsular polysaccharide (Pastorex Cryptococcus; Sanofi-Diagnostics Pasteur,
      Marnes-la-Coquette, France) and compared them with those of tests that use
      polyclonal immune sera (Cryptococcal Antigen Latex Agglutination System, Meridian
      Diagnostics, Inc., Cincinnati, Ohio; and Crypto-LA, International Biological Labs
      Inc., Cranbury, N.J.). The sensitivities and specificities of the tests were
      compared by using purified polysaccharides and yeast suspensions. Clinical
      specimens (131 serum samples, 41 cerebrospinal fluid samples, 34 urine samples,
      and 19 bronchoalveolar lavage samples) from 87 human immunodeficiency virus
      positive subjects with (40 patients) and without (47 patients) culture-proven
      cryptococcosis were retrospectively tested during a blinded study. The effect of
      pronase treatment of samples was assessed for Pastorex Cryptococcus and the
      Cryptococcal Antigen Latex Agglutination System, and the antigen titers were
      compared. Our results show that (i) during the screening, concordance among the
      three tests was 97%; (ii) the use of pronase enhanced both the sensitivities and
      specificities of the Pastorex Cryptococcus test; (iii) titers agreed for 67% of
      the cerebrospinal fluid samples and 60% of the serum samples; and (iv)
      cryptococcosis was detected equally well with Pastorex Cryptococcus and with the
      other tests, whatever the infecting serotype (A, B, or D). The meaning of in
      vitro sensitivity and the relationship between titers and sensitivity are
      discussed. The results show that Pastorex Cryptococcus is a rapid and reliable
      test for the detection of cryptococcal antigen in body fluids and suggest that
      kits cannot be used interchangeably to monitor antigen titers in patients.

PMID- 1400952
TI  - Effects of ascorbic acid on Chlamydia trachomatis infection and on erythromycin
      treatment in primary cultures of human amniotic cells.
AB  - Ascorbic acid (vitamin C) is an essential nutrient for humans. It may also be
      needed by Chlamydia trachomatis, an intracellular bacterium. We investigated the
      effects of vitamin C on the growth of C. trachomatis E/UW-5/Cx in a primary
      culture of human amniotic epithelial cells. The results showed that vitamin C
      enhances C. trachomatis infection at concentrations of 0.2, 0.6, and 1.2 mg/dl (P
      less than 0.001). These three concentrations represent the in vivo concentrations
      of deficiency, normal, and overload levels in serum, respectively. The
      enhancement was dose dependent. However, the growth of C. trachomatis was
      inhibited at vitamin C concentrations of 120 and 1,200 mg/dl. The inhibitory
      effect of erythromycin against C. trachomatis was shown to be reduced in the
      presence of vitamin C at the three concentrations tested (P less than 0.025
      0.001), and MICs were four times greater (1.6 versus 0.4 micrograms/ml). Human
      amniotic cells were tolerant to vitamin C concentrations of up to 1,200 mg/dl.
      The results show that vitamin C may be an important nutrient for C. trachomatis
      and that incorporation of vitamin C in the culture medium may enhance the
      isolation and propagation of C. trachomatis in cell cultures.

PMID- 1400953
TI  - Improvement of simultaneous detection of antibodies to Gag and envelope antigens
      of human T-lymphotropic virus type I by western immunoblot assay.
AB  - To determine seropositivity for human T-lymphotropic virus type I (HTLV-I), we
      attempted to improve the detection system that uses antibody to HTLV-I Env in
      Western immunoblotting (WB) by adding an envelope glycoprotein (gp46) purified
      from the culture fluid of HTLV-I-producing cells by immunoaffinity chromatography
      and gel chromatography. In this WB, 177 of 179 serum samples showing
      seropositivity in an indirect immunofluorescence assay showed positive reactions
      to the gp46 envelope antigen as well as to p19, p24, and p53 Gag antigens. The
      remaining two samples showed negative reactions to p24. False-positive results
      were not found for 533 indirect immunofluorescence assay-negative serum samples,
      although one band to p19 or p24 was observed in 46 of the 533 samples. These 46
      samples did not react to p53 and gp46, suggesting that these samples belonged to
      the indeterminate group in accordance with the criteria proposed by the World
      Health Organization. Therefore, this improved WB can be used for the confirmation
      of seropositivity.

PMID- 1400954
TI  - Comparison of four different enzyme-linked immunosorbent assays for serological
      diagnosis of Salmonella enteritidis infections in experimentally infected
      chickens.
AB  - The program for the eradication of Salmonella enteritidis from chickens in The
      Netherlands is based on bacteriological examination of breeding flocks. There is
      a great need for a specific and sensitive serological screening test. For that
      purpose, we developed four different enzyme-linked immunosorbent assays (ELISAs),
      i.e., an indirect ELISA with S. enteritidis flagellin, an indirect ELISA with S.
      enteritidis lipopolysaccharide, a double-antibody sandwich blocking ELISA that
      uses monoclonal antibodies against S. enteritidis flagellin (GM-DAS blocking
      ELISA), and a double-antibody sandwich ELISA that uses monoclonal antibodies
      against S. enteritidis lipopolysaccharide. In the present study, we compare the
      results of those ELISAs with sera from experimentally infected 1-day-old chickens
      and with sera and eggs from experimentally infected laying hens. Experimental
      infections were induced with strains of S. enteritidis phage types 1 and 2, S.
      typhimurium, and S. panama. Sera were collected up to days 44 and 39 after
      infection from 1-day-old chickens and laying hens, respectively. Only the GM-DAS
      blocking ELISA was able to discriminate between S. enteritidis infections and
      infections with the other serotypes. This ELISA had both a sensitivity and a
      specificity of 100% for all serum samples from experimentally infected chickens.
      A field study is in progress to evaluate whether this test can be implemented in
      the Dutch S. enteritidis eradication program.

PMID- 1400955
TI  - Detection of Mycobacterium tuberculosis in clinical samples by using polymerase
      chain reaction and a nonradioactive detection system.
AB  - A test based on the polymerase chain reaction (PCR) was developed for the
      detection of the Mycobacterium tuberculosis complex in clinical samples. In this
      test, a 245-bp sequence of the insertion element IS986 was amplified and detected
      by agarose gel electrophoresis in the presence of ethidium bromide and by
      Southern blot and dot blot hybridization by using a 188-bp digoxigenin-labeled
      probe. We tested clinical specimens from 227 patients suspected of having
      tuberculosis. These included 102 cerebrospinal fluid, 48 sputum, 18 pleural
      fluid, 5 bronchoalveolar lavage, 18 blood, 7 pus, 8 bone marrow, and 6 urine
      samples and 15 tissue biopsy specimens. We also tested sputum samples from 75
      patients with diseases other than tuberculosis. Sputum samples were first
      decontaminated, and all samples were treated with proteinase K-detergent solution
      to extract the DNA. Part of each sample was spiked with M. tuberculosis to
      provide a semiquantitative assay and to control for the loss of mycobacteria or
      interference with the PCR which may cause false-negative results. One femtogram
      of M. tuberculosis DNA could be detected. PCR was positive for all 32 culture
      positive (for M. tuberculosis) and Ziehl-Neelsen staining (ZN)-positive samples,
      10 of 12 culture-positive and ZN-negative samples, and all 4 culture-negative and
      ZN-positive samples. PCR detected M. tuberculosis complex bacteria in 35 of 178
      culture- and ZN-negative samples. Clinical data supported the diagnosis of
      tuberculosis in the majority of the 35 patients from whom those samples were
      obtained.

PMID- 1400956
TI  - Detection of Babesia bigemina-infected carriers by polymerase chain reaction
      amplification.
AB  - A SpeI-AvaI fragment (0.3 kbp) from pBbi16 (a pBR322 derivative containing a 6.3
      kbp Babesia bigemina DNA insert) was subcloned into the pBluescript phagemid
      vector and was sequenced by the dideoxy-mediated chain termination method. Two
      sets of primers were designed for the polymerase chain reaction (PCR) assay.
      Primer set IA-IB was used to amplify a 278-bp DNA fragment, and primer set IAN
      IBN was used to prepare a probe directed to a site within the PCR-amplified
      target DNA. Digoxigenin-dUTP was incorporated into the probe during the
      amplification reaction. PCR amplification of target DNA obtained from in vitro
      cultured B. bigemina and nucleic acid hybridization of amplified product with the
      nonradioactive DNA probe showed that a 278-bp fragment could be detected when as
      little as 100 fg of parasite genomic DNA was used in the assay. A fragment of
      similar size was amplified from genomic DNAs from several B. bigemina isolates
      but not from DNAs from Babesia bovis, Anaplasma marginale, or six species of
      bacteria or bovine leukocytes. Similarly, the PCR product could be detected in
      DNA samples purified from 200 microliters of blood with a parasitemia of as low
      as 1 in 10(8) cells and which contained an estimated 30 B. bigemina-infected
      erythrocytes. By a direct PCR method, B. bigemina DNA was amplified from 20
      microliters of packed erythrocytes with a calculated parasitemia of 1 in 10(9)
      cells. With the analytical sensitivity level of the PCR-DNA probe assay, six
      cattle with inapparent, 11-month chronic B. bigemina infection were found to be
      positive. No PCR product was observed in bovine blood samples collected from a
      splenectomized, A. marginale-infected bovine, a 4-year chronic B. bovis-infected
      animal, or 20 uninfected cattle from Missouri which were subjected to
      amplification. The PCR-DNA probe assay was shown to be sensitive in detecting
      latently infected cattle. The specificity and high analytical sensitivity of the
      test provide valuable tools for performing large-scale epidemiological studies.

PMID- 1400957
TI  - Latex agglutination-negative methicillin-resistant Staphylococcus aureus
      recovered from neonates: epidemiologic features and comparison of typing methods.
AB  - An unusual strain of methicillin-resistant Staphylococcus aureus (MRSA) was
      repeatedly isolated from infants in a newborn special care unit (NBSC) and a
      newborn intensive care unit. Between January 1989 and March 1990, approximately
      100 isolates from infected or colonized infants were recovered. Surveillance
      cultures taken during this time revealed a 20% colonization rate, which was
      defined as recovery of MRSA from the nares, umbilicus, or groin. Isolates were
      identified as S. aureus by tube coagulase reactivity and heat-stable nuclease
      production but were unreactive in a latex agglutination assay. Representative
      isolates that were collected during the outbreak and that were found to share the
      latex agglutination assay-negative phenotype were compared by antibiogram (12
      isolates), bacteriophage typing (20 isolates), capsular polysaccharide typing (30
      isolates), and plasmid as well as chromosomal DNA analyses (20 isolates). All
      isolates known to be associated with the outbreak had nearly identical
      antibiograms and were notably susceptible to clindamycin. Staphylococcal
      bacteriophage typing was not useful in determining the relatedness of the
      isolates, since the majority were nontypeable. Plasmid pattern analysis revealed
      one large plasmid (approximately 100 kb) of equivalent size among the isolates.
      Capsular polysaccharide typing revealed that 14 of 30 isolates tested were type
      5. Isolates identified in children at two other hospitals in the city which were
      also unreactive by the latex agglutination assay and clindamycin susceptible had
      plasmid and antibiogram patterns identical to those of isolates from the NBSC.
      Pulsed-field gel electrophoresis of restriction enzyme-digested genomic DNAs from
      the outbreak isolates demonstrated identical patterns which could be clearly
      differentiated from those of other unrelated MRSA. The strain from the NBSC is,
      therefore, unique and underscores the need for caution in interpreting the latex
      agglutination reactivities of MRSA isolates.

PMID- 1400958
TI  - Pyrazinamidase, CR-MOX agar, salicin fermentation-esculin hydrolysis, and D
      xylose fermentation for identifying pathogenic serotypes of Yersinia
      enterocolitica.
AB  - We evaluated several simple laboratory tests that have been used to identify
      pathogenic serotypes of Yersinia enterocolitica or to indicate the pathogenic
      potential of individual strains. A total of 100 strains of Y. enterocolitica were
      studied, including 25 isolated during five outbreak investigations, 63 from
      sporadic cases, and 12 from stock cultures. The pyrazinamidase test, which does
      not depend on the Yersinia virulence plasmid, correctly identified 60 of 63 (95%
      sensitivity) strains of pathogenic serotypes and 34 of 37 (92% specificity)
      strains of nonpathogenic serotypes. Salicin fermentation-esculin hydrolysis (25
      degrees C, 48 h) correctly identified all 63 (100% sensitivity) strains of the
      pathogenic serotypes and 34 of 37 (92% specificity) strains of the nonpathogenic
      serotypes. The results of the pyrazinamidase and salicin-esculin tests disagreed
      for only 7 of the 100 strains of Y. enterocolitica, and these would require
      additional testing. Congo red-magnesium oxalate (CR-MOX) agar determines Congo
      red dye uptake and calcium-dependent growth at 36 degrees C, and small red
      colonies are present only if the strain contains the Yersinia virulence plasmid.
      This test has proven to be extremely useful for freshly isolated cultures, but
      only 15 of 62 strains of pathogenic serotypes that had been stored for 1 to 10
      years were CR-MOX positive. None of the 16 strains of Y. enterocolitica serotype
      O3 fermented D-xylose, so this test easily differentiated strains of this
      serotype, which now appears to be the most common in the United States. Although
      antisera that can actually be used to serotype strains of Y. enterocolitica are
      not readily available, the four simple tests described above can be used to
      screen for pathogenic serotypes.

PMID- 1400959
TI  - Genotyping Naegleria spp. and Naegleria fowleri isolates by interrepeat
      polymerase chain reaction.
AB  - All six Naegleria species recognized to date were studied by interrepeat
      polymerase chain reaction (PCR). Priming at repeat sequences, which are known to
      be variable among eukaryotes, yielded electrophoretic DNA banding patterns that
      were specific for any single species. With a single PCR and simple gel
      electrophoresis, species determination could be performed in less than 1 day.
      Unambiguous discrimination between the pathogen N. fowleri and nonpathogenic
      Naegleria species appeared to be possible. Analysis of DNAs obtained from 20
      separate isolates of N. fowleri revealed that geographic variation of the genetic
      fingerprints rarely occurs. All but 3 of 20 isolates of N. fowleri which were
      investigated showed identical banding patterns; for two isolates from New Zealand
      and one from Australia, a limited number of additional bands was detected,
      independent of the PCR primers used. These data corroborate previous findings on
      the genetic stability of pathogenic N. fowleri.

PMID- 1400960
TI  - Detection of binding antibodies to native and recombinant human immunodeficiency
      virus type 1 envelope glycoproteins following recombinant gp160 immunization
      measured by flow cytometry and enzyme immunoassays. The AIDS Vaccine Clinical
      Trials Network.
AB  - The ability of antibody induced by vaccination with recombinant gp160 (rgp160) to
      bind to native and recombinant human immunodeficiency virus type 1 (HIV-1)
      envelope glycoproteins was measured. Thirty-three HIV-1-seronegative healthy
      adult volunteers were injected four times with 40 or 80 micrograms of an HIV-1LAV
      envelope glycoprotein candidate vaccine per dose. The vaccine consisted of rgp160
      produced in insect tissue culture cells infected with a recombinant baculovirus
      which contains the gp160 gene from the HIV-1LAV strain. By using a flow
      cytometric indirect immunofluorescence assay (FIFA) to detect vaccine-induced
      antibody to native envelope glycoprotein expressed by target cells infected with
      HIV-1IIIB, sera from 9 of the 33 vaccinees were positive. These included sera
      from eight vaccinees which stained HIV-1IIIB-infected cells and sera from two
      vaccinees which stained target cells infected with HIV-1MN, a heterologous virus
      strain. None of the sera stained cells infected with the HIV-1RF strain. Envelope
      glycoprotein-binding antibody was more frequently detectable in an enzyme-linked
      immunosorbent assay (ELISA) by using rgp160 compared with that which was
      detectable in the FIFA with uninfected target cells which were pulsed with rgp160
      antigen. Positive correlations were observed between the rgp160 FIFA and a whole
      virus-lysate enzyme immunoassay, between the rgp160 FIFA and the rgp160 ELISA,
      and between the rgp160 ELISA and the whole-virus-lysate enzyme immunoassay. The
      ability of sera from some volunteers who received rgp160 vaccine to bind to HIV-1
      infected cells suggests that further studies with this vaccine should be done.

PMID- 1400961
TI  - Specific detection of Campylobacter jejuni and Campylobacter coli by using
      polymerase chain reaction.
AB  - Development of a routine detection assay for Campylobacter jejuni and
      Campylobacter coli in clinical specimens was undertaken by using the polymerase
      chain reaction (PCR). An oligonucleotide primer pair from a conserved 5' region
      of the flaA gene of C. coli VC167 was used to amplify a 450-bp region by PCR. The
      primer pair specifically detected 4 strains of C. coli and 47 strains of C.
      jejuni; but it did not detect strains of Campylobacter fetus, Campylobacter lari,
      Campylobacter upsaliensis, Campylobacter cryaerophila, Campylobacter butzleri,
      Campylobacter hyointestinalis, Wolinella recta, Helicobacter pylori, Escherichia
      coli, Shigella spp., Salmonella spp., Vibrio cholerae, Citrobacter freundii, or
      Aeromonas spp. By using a nonradioactively labeled probe internal to the PCR
      product, the assay could detect as little as 0.0062 pg of purified C. coli DNA,
      or the equivalent of four bacteria. In stools seeded with C. coli cells, the
      probe could detect between 30 and 60 bacteria per PCR assay. The assay was also
      successfully used to detect C. coli in rectal swab specimens from experimentally
      infected rabbits and C. jejuni in human stool samples.

PMID- 1400962
TI  - Comparison of polymerase chain reaction and culture for detection of Borrelia
      burgdorferi in naturally infected Peromyscus leucopus and experimentally infected
      C.B-17 scid/scid mice.
AB  - Culture and the polymerase chain reaction (PCR) were compared for detection of
      Borrelia burgdorferi infection in wild-caught Peromyscus leucopus and
      experimentally inoculated C.B-17 scid/scid (severe combined immunodeficient)
      mice. PCR targeted highly conserved regions of the ospA gene and could detect one
      to five cultured organisms and 10 to 50 copies of molecularly cloned ospA DNA.
      Organs (kidney, spleen, and urinary bladder) and/or ear biopsy samples were
      obtained from 108 captured P. leucopus mice, and tissues were obtained from 7
      experimentally inoculated mice. A simple sample-processing procedure with
      proteinase K and detergent treatment was used in the PCR analysis. Overall, B.
      burgdorferi was detected in 29 of 108 (27%) P. leucopus mice by culture and in 31
      of 108 (29%) mice by PCR. As assessed by the kappa statistic, agreement between
      PCR and culture was high for ear and bladder (kappa = 0.80 and 0.65,
      respectively) and low for kidney and spleen (kappa = 0.37 and 0.03,
      respectively). While concordant results were obtained from 98 animals, PCR
      detected B. burgdorferi from 6 additional mice for which cultures were negative
      and culture detected B. burgdorferi from 4 animals which were PCR negative.
      Further phenol-chloroform extraction of DNA in a limited number of samples
      improved the sensitivity of PCR compared with that of culture. These results
      indicate that PCR may be as sensitive as culture for detecting B. burgdorferi in
      ear samples and that PCR analysis is suitable for establishing the infection
      status of animals in mark-release-recapture studies.

PMID- 1400963
TI  - Outer membrane protein profiles and multilocus enzyme electrophoresis analysis
      for differentiation of clinical isolates of Proteus mirabilis and Proteus
      vulgaris.
AB  - Outer membrane protein (MP) profiles and multilocus enzyme electrophoresis (MEE)
      analysis were used as tools for differentiating clinical isolates of Proteus spp.
      Fourteen distinct MP profiles were established by sodium dodecyl sulfate-urea
      polyacrylamide gel electrophoresis in 54 clinical isolates of Proteus spp. (44
      strains identified as P. mirabilis and 10 strains identified as P. vulgaris).
      Forty-one isolates of P. mirabilis and eight isolates of P. vulgaris were grouped
      within six and three MP profiles, respectively. The remaining P. mirabilis and P.
      vulgaris isolates had unique profiles. MEE analysis was used to further
      discriminate among the strains belonging to the same MP groups. Thirty-five
      distinct electrophoretic types (ETs) were identified among P. mirabilis isolates.
      The isolates of P. mirabilis from the four most common MP groups were subgrouped
      into 30 ETs. All of the P. vulgaris strains had unique ETs. The results suggest
      that upon biochemical classification of Proteus isolates as P. mirabilis or P.
      vulgaris, further differentiation among strains of the same species can be
      obtained by the initial determination of MP profiles followed by MEE analysis of
      strains with identical MPs.

PMID- 1400965
TI  - Description and evaluation of the semiautomated 4-hour rapid ID 32 Strep method
      for identification of streptococci and members of related genera.
AB  - The rapid ID 32 Strep system (bioMerieux, La Balme les Grottes, France) is a new
      system which allows the identification in 4 h of most streptococci and members of
      related genera encountered in medical and veterinary bacteriology. Four hundred
      thirty-three isolates first identified by conventional methods and belonging to
      the genera Streptococcus, Lactococcus, Enterococcus, Aerococcus, Gemella,
      Leuconostoc, Erysipelothrix, Gardnerella, and Listeria were tested. Overall,
      rapid ID 32 Strep correctly identified 413 (95.3%) of the strains, with 109
      (25.1%) requiring extra tests for complete identification. Sixteen strains (3.7%)
      were not identified, and 4 (1.0%) were misidentified. The rapid ID 32 Strep
      system is a suitable alternative for rapid identification of members of the genus
      Streptococcus and of related genera.

PMID- 1400964
TI  - Detection of Mycoplasma pneumoniae in clinical samples from pediatric patients by
      polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) technique was used to detect Mycoplasma
      pneumoniae DNA in clinical samples (nasopharyngeal aspirations or bronchoalveolar
      lavages) obtained from 100 children, 1 month to 16 years old. PCR allowed the
      detection of M. pneumoniae DNA from 20 out of the 100 patients studied. In 16
      cases, PCR positivity was associated with acute respiratory symptomatology. For
      five PCR-positive patients, a positive culture or a serological response
      evidenced acute M. pneumoniae infections. A lack of antibody response was
      observed particularly with immunocompromised children and infants less than 12
      months old. The amount of M. pneumoniae DNA in the PCR was estimated in a
      semiquantitative way by comparison of its hybridization signal with those
      obtained for 100, 10, and 1 color-changing unit (CCU) of the M. pneumoniae FH
      strain. Small amounts (less than or equal to 10(2) CCU/ml) of M. pneumoniae were
      found in samples from asymptomatic patients, while larger amounts (greater than
      or equal to 10(2) to greater than or equal to 10(4) CCU/ml) were found for 8 out
      of 10 patients with acute pneumonia.

PMID- 1400966
TI  - Purification, characterization, and seroactivity of a 20-kilodalton Brucella
      protein antigen.
AB  - An internal protein was purified from cell extracts of Brucella melitensis B115
      by a combination of preparative isoelectric focusing and high-performance size
      exclusion chromatography. The protein has an apparent molecular mass of 230 kDa
      as determined by size exclusion chromatography. The protein was resolved to a
      single band of 20 kDa after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The native protein had an isoelectric point of 4.9. The N
      terminal sequence of the 20-kDa protein was determined. The 20-kDa protein has
      been identified as antigen A-2 with a previously described anti-antigen A-2 serum
      (B. Stemshorn, K. Nielsen, and B. Samagh, Can. J. Comp. Med. 45:77-81, 1981).
      Antigen A-2 reacted with sera from infected sheep in immunoblotting and may be
      useful in developing diagnostic tests for brucellosis.

PMID- 1400968
TI  - Initial testing of a novel urine culture device.
AB  - The Diaslide urine culture device consists of a hinged case containing two
      opposing agar media separated by a sampler with a handle at one end and two bent
      sampler tips at the opposite end. The tips of the sampler are first dipped into
      the urine. The sampler is then pulled out through the casing, simultaneously
      inoculating both agar surfaces with a streaking dilution. As a result, individual
      colonies can be observed even when bacterial concentrations exceed 10(6) CFU/ml.
      The number of colonies on the Diaslide correlated linearly with CFU per
      milliliter as determined by dilution plating. The clinical performance of the
      Diaslide was compared with those of ordinary dipslides and conventional cultures
      with a sample of 473 prescreened hospital urine specimens. The sensitivity,
      specificity, and positive predictive value of Diaslide versus those of culture at
      the 10(4)-CFU/ml cutoff level were 97.5, 98.3, and 98.3%, respectively, compared
      with 98.8, 95.7, and 97.2%, respectively, for dipslide versus culture. Similar
      results were found at the 10(5)-CFU/ml cutoff level. Only 5.5% of the Diaslides
      required subculturing, compared with 14.7 and 9.4% of the dipslides and
      conventional cultures, respectively. The Diaslide proved more convenient than an
      ordinary dipslide for sampling low volumes of urine. These data suggest that the
      Diaslide is a simple, effective device for culturing of urine specimens.

PMID- 1400967
TI  - Detection of pathogenic Yersinia enterocolitica by polymerase chain reaction and
      digoxigenin-labeled polynucleotide probes.
AB  - Yersinia enterocolitica is widespread in nature, but only a few bioserotypes are
      involved in human infections. Pigs are considered to be the major reservoirs of
      pathogenic strains. It is essential to have an accurate and rapid method for the
      detection of pathogenic yersiniae. To achieve this objective, 19-base synthetic
      oligonucleotide primers were used in a polymerase chain reaction (PCR) to detect
      the ail gene (which is conserved only in pathogenic strains) in strains of Y.
      enterocolitica and related species originating from pigs or pork products.
      Digoxigenin-labeled probes derived from the ail, inv, and yst genes were also
      evaluated on these strains. The PCR amplified a 273-bp fragment of the ail gene
      involved in eukaryotic cell invasion and serum resistance. The PCR detected
      template DNA only in strains of Y. enterocolitica traditionally classified as
      human pathogens but not in biotype 1A strains and related species. Other members
      of the family Enterobacteriaceae were also negative for the target gene. The
      digoxigenin-labeled ail probe gave identical results to the PCR. By use of this
      nonisotopic method, inv-homologous DNA was detected only among yersiniae, except
      for Y. ruckeri. Although all pathogenic serotypes of Y. enterocolitica were
      positive for the heat-stable enterotoxin yst gene, two strains of biotype 1A, one
      Y. intermedia strain, and six other species of the Enterobacteriaceae were also
      positive. Our results support the notion that pigs constitute an important
      reservoir of pathogenic Y. enterocolitica and that the inv-homologous sequence is
      Yersinia specific.

PMID- 1400969
TI  - In vitro antimicrobial susceptibility testing of Borrelia burgdorferi: a
      microdilution MIC method and time-kill studies.
AB  - The susceptibility of Borrelia burgdorferi, the causative agent of Lyme
      borreliosis, to various antimicrobial agents varies widely among published
      studies. These differences are probably due in part to variations in
      susceptibility testing techniques and growth endpoint determinations. We
      developed a microdilution method for determining the MICs of antibiotics against
      B. burgdorferi. The method incorporated BSK II medium, a final inoculum of 10(6)
      cells per ml, and a 72-h incubation period and was found to be simple and highly
      reproducible. A variety of antibiotics and strains of B. burgdorferi and one
      strain of Borrelia hermsii were examined by this method. MICs of penicillin,
      ceftriaxone, and erythromycin for the B31 strain of B. burgdorferi were 0.06,
      0.03, and 0.03 microgram/ml, respectively. We compared the MICs obtained by the
      microdilution method with those obtained by a macrodilution method using similar
      criteria for endpoint determinations and found the values obtained by both
      methods to be in close agreement. To further investigate the bactericidal
      activities of penicillin, ceftriaxone, and erythromycin against strain B31, we
      used subsurface plating to determine MBCs and we also performed time-kill
      studies. The MBCs of penicillin, ceftriaxone, and erythromycin were 0.125, 0.03,
      and 0.06 micrograms/ml, respectively. Time-kill curves demonstrated a greater
      than or equal to 3-log10-unit killing after 72 h with penicillin, ceftriaxone,
      and erythromycin; ceftriaxone provided the greatest reduction in CFU. The
      described methods offer a more standardized and objective approach to
      susceptibility testing of B. burgdorferi.

PMID- 1400970
TI  - Identification of Mycobacterium avium complex strains and some similar species by
      high-performance liquid chromatography.
AB  - Strains of Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium
      scrofulaceum, Mycobacterium xenopi, and Mycobacterium gordonae were identified by
      high-performance liquid chromatography (HPLC) analysis of mycolic acids as
      bromophenacyl esters. HPLC criteria were used to develop a flow chart
      identification scheme, which was evaluated in our laboratory with a set of 234
      strains representing five species and a hitherto undescribed species. Correct
      identifications of M. gordonae and M. xenopi were easily made. Flow chart
      differentiation of M. avium, M. intracellulare, and M. scrofulaceum was done with
      97.9, 97.5, and 89.2% accuracies, respectively. Independent evaluation of the
      flow chart at a separate laboratory demonstrated an overall identification
      accuracy of 97% for M. avium complex. Strains that have been described
      biochemically as being intermediate between M. avium-M. intracellulare and M.
      scrofulaceum were identified as one or the other of these known species. Strains
      which were negative with the species-specific radioactive probe for M. avium
      complex but which were positive with the nonradioactive SNAP X probe were usually
      identified as M. intracellulare and M. scrofulaceum but rarely as M. avium.

PMID- 1400971
TI  - Purification of listeriolysin O and development of an immunoassay for diagnosis
      of listeric infections in sheep.
AB  - A protein of 58,000-Da molecular mass was purified from the supernatant fluid of
      a dialysis sac culture of Listeria monocytogenes by cation-exchange
      chromatography. The purified protein, homogeneous by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and possessing the characteristics of
      listeriolysin O (LLO), was used to develop an indirect enzyme-linked
      immunosorbent assay. Anti-LLO antibodies were shown to be consistently produced
      in sheep after experimental challenge with L. monocytogenes serovar 4b. The assay
      also successfully detected and measured specific anti-LLO antibodies in the sera
      of silage-fed sheep among which listeric enteritis and abortions had occurred.

PMID- 1400972
TI  - Comparison of five methods, including the PDM Epsilometer test (E test), for
      antimicrobial susceptibility testing of Pseudomonas aeruginosa.
AB  - The antimicrobial susceptibilities of 100 clinical isolates of Pseudomonas
      aeruginosa to six antipseudomonal antibiotics were tested by five methods: the
      National Committee for Clinical Laboratory Standards (NCCLS) methods for broth
      microdilution, agar dilution, and agar disk diffusion; the Vitek Automicrobic
      System method (Vitek Systems, Hazelwood, Mo.); and the PDM Epsilometer test (E
      test) (AB Biodisk, Solna, Sweden). The E test results showed excellent
      correlation with agar dilution results, with over 90% agreement within 1 doubling
      dilution between the E test and reference agar dilution MICs for all
      antimicrobial agents tested. The E test results also showed good correlation with
      the results from the reference agar disk diffusion method, with 90 to 99%
      complete agreement and 100% essential agreement on categories for all antibiotics
      tested (essential agreement is the agreement obtained when minor discrepancies
      are ignored). Comparison of categories with the E test and broth microdilution
      methods, using the broth microdilution method as the reference method, gave only
      59% complete agreement for gentamicin, with 28 minor discrepancies and 13 very
      major discrepancies. Some discrepancies were observed between results from the E
      test and broth methods for gentamicin, with the broth microdilution and Vitek
      methods giving higher MICs than the E test and other methods using agar. The most
      recent NCCLS guidelines for broth dilution testing have reduced the recommended
      levels of cation supplementation, which may enhance future agreement between
      results for the aminoglycosides and P. aeruginosa on broth and on agar. We found
      that the E test offers a simple, labor-efficient, and accurate method for MIC
      determination on an agar medium.

PMID- 1400973
TI  - Comparison of the Sceptor Pseudomonas Plus MIC Panel with agar dilution for
      susceptibility testing of Pseudomonas aeruginosa.
AB  - The antimicrobial susceptibilities of 100 clinical isolates of Pseudomonas
      aeruginosa to gentamicin, amikacin, tobramycin, ticarcillin, piperacillin, and
      ceftazidime were determined by using the Sceptor system (BBL Microbiology
      Systems, Cockeysville, Md.), and the results were compared with those obtained
      using the National Committee for Clinical Laboratory Standards reference agar
      dilution method. Excellent correlation was observed for the aminoglycosides, with
      greater than 95% agreement within 1 doubling dilution of the reference agar
      dilution MIC, while ticarcillin and piperacillin showed lower percent agreement
      values of 91 and 88%, respectively.

PMID- 1400974
TI  - Identification of Streptococcus pneumoniae with a DNA probe.
AB  - The Accuprobe Streptococcus pneumoniae Culture Identification Test (Gen-Probe,
      Inc.) was evaluated with 172 isolates of S. pneumoniae and 204 nonpneumococcal
      isolates. The sensitivity and specificity of the Accuprobe test were 100%.
      Optimum results were obtained when four or more discrete colonies were selected
      for testing. The Accuprobe test was determined to be an accurate and rapid method
      for identification of S. pneumoniae.

PMID- 1400976
TI  - Vibrio-associated gastroenteritis in the lower Cross-River Basin of Nigeria.
AB  - A total of 120 Vibrio species were isolated from 588 patients with acute
      diarrheal disease during an outbreak of gastrointestinal tract infections at
      different locations in the lower Cross River Basin of Nigeria. Vibrio cholerae
      O1, biotype El Tor, serotype Ogawa, was the prominent organism isolated from the
      Vibrio-associated diarrheal cases. During the 3 months of study, V. cholerae non
      O1 was recovered from 10 patients while Vibrio parahaemolyticus was recovered
      from 19 patients. The significance of this study is the recognition that there is
      an ecological niche which supports V. cholerae non-O1 and V. parahaemolyticus in
      the Cross River Basin of Nigeria.

PMID- 1400975
TI  - Identification of Pseudomonas aeruginosa by using a disk of phenanthroline and 9
      chloro-9-[4-(diethylamino)phenyl]-9,10-dihydro-10-phenylacridine hydrochloride
      and by cell agglutination testing with monoclonal antibodies.
AB  - To establish a simple identification procedure for Pseudomonas aeruginosa, we
      developed a disk consisting of phenanthroline and 9-chloro-9-[4
      (diethylamino)phenyl]-9,10-dihydro-10- phenylacridine hydrochloride (PC disk).
      Nine of 248 P. aeruginosa isolates and all other oxidase-positive gram-negative
      isolates (143 isolates) had clear inhibition zones around the PC disk. Of these
      nine P. aeruginosa isolates, seven produced a blue, blue-green, or green pigment
      on Mueller-Hinton agar after 24 h of incubation. The sensitivity and specificity
      of the PC disk susceptibility test in combination with pyocyanin production were
      99 and 100%, respectively. Ten P. aeruginosa isolates showed no agglutination
      reactions with monoclonal antibodies against P. aeruginosa (96% sensitivity and
      100% specificity).

PMID- 1400977
TI  - Seroprevalence of enteric and nonenteric adenoviruses in Bangladesh.
AB  - Single serum samples obtained from infants between 0 and 24 months of age
      admitted to a diarrheal disease hospital in Bangladesh were tested for the
      presence of adenovirus-specific immunoglobulin G (IgG) and IgA antibodies by
      using enzyme immunoassay and neutralizing antibodies to adenovirus types 2, 40,
      and 41. IgG antibodies were more prevalent than IgA antibodies, and neutralizing
      activity to enteric adenovirus was found in serum samples from 50% of infants who
      had reached 2 years of age.

PMID- 1400978
TI  - Optimum use of selective plated media in primary processing of respiratory tract
      specimens from patients with cystic fibrosis.
AB  - A total of 258 respiratory tract specimens from patients with cystic fibrosis
      were inoculated onto nine different plated media, and the rates of recovery of
      potential pathogens were compared. Media included sheep blood agar, enriched
      chocolate agar, MacConkey agar for gram-negative bacilli, chocolate agar
      containing bacitracin for Haemophilus spp., bromcresol green agar for yeasts,
      cetrimide agar for Pseudomonas spp., sheep blood agar containing colistin and
      nalidixic acid for gram-positive cocci, mannitol salt agar for Staphylococcus
      aureus, and oxidation-fermentation agar containing 300 U of polymyxin B per ml
      and 2 U of bacitracin per ml (OF-PBL medium) for Pseudomonas cepacia. With two
      exceptions, all of these media proved useful in recovering potential pathogens
      from respiratory tract specimens from patients with cystic fibrosis. The two
      exceptions were cetrimide agar and colistin-nalidixic acid-supplemented sheep
      blood agar, which were found to be superfluous. In addition, the results of this
      study further delineated the prevalence of selected bacteria and fungi in
      respiratory tract secretions from patients with cystic fibrosis. In rank order of
      frequency of isolation, we recovered isolates of Pseudomonas aeruginosa,
      Haemophilus parainfluenzae, Candida albicans, S. aureus, Haemophilus influenzae,
      molds, members of the family Enterobacteriaceae, yeasts other than Candida
      albicans, miscellaneous gram-negative bacilli, beta-hemolytic streptococci, P.
      cepacia, and Streptococcus pneumoniae.

PMID- 1400979
TI  - Time to detection of positive BacT/Alert blood cultures and lack of need for
      routine subculture of 5- to 7-day negative cultures.
AB  - Consecutive BacT/Alert blood cultures which were instrument negative following a
      7-day incubation were subcultured. Eighteen (0.2%) of 11,476 bottles had growth
      on subculture. Eleven of these eighteen isolates were considered contaminants on
      the basis of the identity of the organism and lack of other positive blood
      cultures from the same patient. In addition, analysis of time to instrument
      detection for approximately 2,900 positive blood cultures indicates that 5 or 6
      days of incubation is sufficient for the routine detection of clinically
      significant organisms from BacT/Alert blood cultures. These data indicate that
      subculture of 5- to 7-day instrument-negative BacT/Alert blood culture bottles is
      not necessary.

PMID- 1400980
TI  - Septicemia with Ewingella americana.
AB  - Ewingella americana was isolated from two blood cultures from a 75-year-old male
      after cholecystectomy. The characteristics of this strain are compared with the
      reported biochemical characteristics of 44 American strains. Previously described
      infections and pseudoinfections with E. americana are reviewed.

PMID- 1400981
TI  - Colony morphotype on Sabouraud-triphenyltetrazolium agar: a simple and
      inexpensive method for Candida subspecies discrimination.
AB  - A new method of Candida subspecies discrimination on Sabouraud
      triphenyltetrazolium agar is reported. Five hundred sixty-two strains of Candida
      and Torulopsis glabrata, previously identified by conventional mycological
      methods, were studied. Each strain received a three-letter code and a number
      based on its colonial morphology. Sixteen morphotypes were found for Candida
      albicans, 6 were found for Candida parapsilosis, 4 were found for both Candida
      guilliermondii and Candida krusei, and 12 were found for Candida tropicalis. None
      of the 56 T. glabrata strains studied grew on this agar. A reproducibility of 95%
      was found for C. albicans. The simplicity and low cost could make this method
      useful for typing Candida spp.

PMID- 1400982
TI  - Evaluation of manufacturer's recommended growth value thresholds for BACTEC
      media.

PMID- 1400983
TI  - Polymerase chain reaction for detection of Leptospira spp. in clinical samples.
AB  - A sensitive assay for Leptospira spp., the causative agent of leptospirosis, was
      developed on the basis of the polymerase chain reaction (PCR). A 331-bp sequence
      from the Leptospira interrogans serovar canicola rrs (16S) gene was amplified,
      and the PCR products were analyzed by DNA-DNA hybridization by using a 289-bp
      fragment internal to the amplified DNA. Specific PCR products also were obtained
      with DNA from the closely related nonpathogenic Leptospira biflexa but not with
      DNA from other spirochetes, such as Borrelia burgdorferi, Borrelia hermsii,
      Treponema denticola, Treponema pallidum, Spirochaeta aurantia, or more distant
      organisms such as Escherichia coli, Staphylococcus aureus, Mycobacterium
      tuberculosis, and Proteus mirabilis. The assay was able to detect as few as 10
      bacteria. Leptospira DNA was detected in urine from experimentally infected mice.
      In addition, the test was found to be suitable for diagnosing leptospirosis in
      humans. Cerebrospinal fluid and urine from patients with leptospirosis were
      positive, whereas samples from control uninfected patients were negative.

PMID- 1400984
TI  - Growth of Porphyromonas gingivalis, Treponema denticola, T. pectinovorum, T.
      socranskii, and T. vincentii in a chemically defined medium.
AB  - A chemically defined medium, OMIZ (Oral Microbiology and Immunology, Zurich)-W1
      was developed. Medium OMIZ-W1 supports the long-term proliferation of a wide
      range of oral anaerobes, including representative strains of four Treponema
      species and Porphyromonas gingivalis. High concentrations of ascorbic acid and
      ammonium ions proved to be important for the growth of these organisms. T.
      denticola CD-1 grew in the absence of polyamines and long-chain fatty acids, T.
      pectinovorum and T. socranskii required polyamines, whereas T. vincentii depended
      on both polyamines and lecithin for growth. Specific requirements for purines
      and/or pyrimidines were detected, and these requirements could be used to
      distinguish Haemophilus-Actinobacillus group organisms. Some strains of P.
      gingivalis grew without vitamin K, while others were not satisfied by menadione
      but required its precursor 1,4-dihydroxy-2-naphthoic acid. Protoporphyrin IX or
      hemin equally satisfied the porphyrin requirements of P. gingivalis and
      Bacteroides forsythus, whereas ferrous sulfate was more efficiently used as a
      source of iron than was hemin. The cellular cohesiveness of P. gingivalis
      increased with high concentrations of hemin in the growth medium. Prevotella
      intermedia, B. forsythus, and several strains of P. gingivalis were more
      fastidious and required a protein or serum supplement to grow in medium OMIZ-W1.

PMID- 1400985
TI  - Evaluation of a cold-adapted influenza B/Texas/84 reassortant virus (CRB-87)
      vaccine in young children.
AB  - A cold-adapted (ca) influenza B reassortant virus vaccine that contained the six
      internal RNA segments from influenza B/Ann Arbor/1/66 ca virus and the
      neuraminidase and hemagglutinin genes from wild-type influenza B/Texas/1/84 virus
      was evaluated in children ranging in age from 8 months to 14 years. The children
      were vaccinated intranasally with doses ranging from 10(3.2) to 10(6.2) 50%
      tissue culture infective doses (TCID50). Thirty children were seropositive, and
      26 were seronegative. Thirty-three children participated as unvaccinated
      controls. The vaccine was well tolerated by both seronegative and seropositive
      children. The amount of virus required to infect 50% of seronegative children was
      approximately 10(4.5) TCID50. Vaccine viruses recovered from airway secretions
      retained temperature-sensitive and cold-adapted characteristics. The results of
      this study indicate that the vaccine virus, influenza B/Texas/84 ca reassortant
      virus, is attenuated, immunogenic, and phenotypically stable when given to young
      seronegative children.

PMID- 1400986
TI  - Confirmatory polymerase chain reaction testing for Chlamydia trachomatis in first
      void urine from asymptomatic and symptomatic men.
AB  - First-void urine specimens from 683 men (592 without symptoms) were tested for
      Chlamydia trachomatis by a polymerase chain reaction (PCR) with KL1 and KL2
      plasmid primers and by a Chlamydiazyme enzyme immunoassay (EIA). Thirty-seven
      specimens were confirmed to be positive by using the EIA blocking reagent and a
      second set of plasmid primers (T1 and T2). By comparing unconfirmed PCR results
      (KL1 and KL2 primers only) with the blocked Chlamydiazyme EIA results, the
      sensitivity and specificity of PCR were 100% (37 of 37 specimens) and 99.5% (643
      of 646 specimens), respectively. Three additional specimens were negative by EIA
      but positive by PCR and were confirmed to be positive with primers T1 and T2. Two
      of the three specimens were from men with symptoms. The confirmatory PCR assay
      performed equally well in detecting positive specimens from symptomatic (31 of
      31) and asymptomatic (9 of 9) men. Comparison of confirmatory testing of first
      void urine specimens by PCR and EIA showed that PCR was 100% sensitive (40 of 40
      specimens) and that the EIA was 92.5% sensitive (37 of 40 specimens) but that the
      assays were equally specific (100%).

PMID- 1400987
TI  - Flow cytometric assay for quantifying opsonophagocytosis and killing of
      Staphylococcus aureus by peripheral blood leukocytes.
AB  - We describe a novel flow cytometric method for quantifying opsonophagocytosis and
      killing of Staphylococcus aureus in cell-rich plasma obtained after dextran
      sedimentation of erythrocytes. To analyze opsonophagocytosis, phagocytes were
      labeled with a phycoerythrin-conjugated monoclonal antibody and were incubated
      with viable staphylococci containing carboxyfluorescein as a vital fluorescent
      dye. Phagocytosing cells assumed a dual, orange-green fluorescence. The relative
      numbers of bacteria associating with phagocytes could be determined by
      quantifying the decrease of free green fluorescent particles. A parallel
      incubation of fluorescent bacteria with unlabeled cell-rich plasma was performed
      to assess phagocytic killing. Blood cells were lysed with 3-[(3-cholamidopropyl)
      dimethyl-ammonio]-1-propanesulfonate. This detergent spared viable bacteria, and
      residual green fluorescent particles were counted. The decrease in the number of
      these particles relative to the controls yielded the degree of killing. At
      bacteria-to-phagocyte ratios of 1:1 and 10:1, approximately 36 and 75% of the
      phagocytes participated in opsonophagocytosis, respectively. Over 90% of the
      staphylococci were phagocyte associated after 30 to 60 min. Killing rates were on
      the order of 66% +/- 12% and 80% +/- 7% after 1 and 2 h of incubation,
      respectively. These numbers, which were confirmed by colony countings, were
      significantly lower than those reported in the majority of past reports.

PMID- 1400989
TI  - The plastic envelope method, a simplified technique for culture diagnosis of
      trichomoniasis.
AB  - Although culture of Trichomonas vaginalis is more sensitive than wet mounts in
      the diagnosis of trichomoniasis, the lack of convenience of culture prevents it
      from being widely used. To improve the acceptability of diagnosis by culture, a
      plastic envelope method (PEM) was devised. PEM permits both immediate examination
      and culture in one self-contained system. The medium consists of dry ingredients
      that are reconstituted with water before use. The effectiveness of immediate
      examinations by PEM was compared with that of wet mounts, and the effectiveness
      of culture by PEM was compared with that of culture in Trichomonas Medium No. 2
      (Oxoid). Of 710 vaginal secretion specimens from symptomatic and asymptomatic
      women that were tested by the four methods, 62 (9%) were positive for T.
      vaginalis. The sensitivity was 66% by wet mount, 66% by immediate examination by
      PEM, 89% by cultures in Oxoid medium, and 97% by culture by PEM. The two culture
      methods had equivalent sensitivities but were significantly (P less than 0.0001)
      more sensitive than the two immediate methods. The combined immediate examination
      by PEM plus culture was more convenient to use than wet mounts plus culture in
      Oxoid medium. The long shelf-life of PEM's dry medium and its anticipated low
      cost are additional advantages.

PMID- 1400988
TI  - Cell-mediated and humoral immune responses induced by scarification vaccination
      of human volunteers with a new lot of the live vaccine strain of Francisella
      tularensis.
AB  - Tularemia is a disease caused by the facultative intracellular bacterium
      Francisella tularensis. We evaluated a new lot of live F. tularensis vaccine for
      its immunogenicity in human volunteers. Scarification vaccination induced humoral
      and cell-mediated immune responses. Indications of a positive immune response
      after vaccination included an increase in specific antibody levels, which were
      measured by enzyme-linked immunosorbent and immunoblot assays, and the ability of
      peripheral blood lymphocytes to respond to whole F. tularensis bacteria as recall
      antigens. Vaccination caused a significant rise (P less than 0.05) in
      immunoglobulin A (IgA), IgG, and IgM titers. Lymphocyte stimulation indices were
      significantly increased (P less than 0.01) in vaccinees 14 days after
      vaccination. These data verify that this new lot of live F. tularensis vaccine is
      immunogenic.

PMID- 1400990
TI  - Evaluation of an immunoenzymatic assay detecting specific anti-Toxocara
      immunoglobulin E for diagnosis and posttreatment follow-up of human toxocariasis.
AB  - In order to complete the immunodiagnosis of human toxocaral disease, an
      immunoenzymatic assay with excretory-secretory antigens from Toxocara canis
      larvae was developed for the detection of specific immunoglobulin E (sIgE enzyme
      linked immunosorbent assay [ELISA]). The specificity of the assay was evaluated
      in patients presenting with various allergic or helminthic diseases. The
      sensitivity was assessed in patients exhibiting clinical and biological symptoms
      indicative of toxocariasis, serodiagnosis of which was made by the Western blot
      (WB; immunoblot) procedure that used the same antigen as that used in the sIgE
      ELISA but that detected specific IgG. The value of the sIgE ELISA for
      posttreatment follow-up was tested in two groups of patients: one group was
      treated with diethylcarbamazine; the other group was not treated with DEC.
      Results showed that the specificity and sensitivity of the sIgE ELISA were
      moderate. Thus, the sIgE ELISA appeared to be insufficient for properly ensuring
      the serodiagnosis of toxocariasis when it is used alone. However, sIgE ELISA
      might be an interesting complementary method for the detection of specific IgG.
      It was the only assay that was found to be positive in sera from some
      hypereosinophilic patients. sIgE ELISA values decreased significantly among the
      patients treated with DEC, indicating that this test would be useful for
      posttreatment follow-up assessment.

PMID- 1400992
TI  - Broth microdilution testing of Haemophilus influenzae with haemophilus test
      medium versus lysed horse blood broth. Canadian Haemophilus Study Group.
AB  - Broth microdilution testing of 702 community-acquired isolates of Haemophilus
      influenzae from across Canada was performed with both Mueller-Hinton broth
      supplemented with 3% lysed horse blood broth (LHB) (BBL Microbiology Systems,
      Cockeysville, Md.) and haemophilus test medium (HTM). The prevalence of beta
      lactamase production was found to be 26% with no regional variation. MICs
      determined with LHB tended to be higher than those with HTM, but interpretive
      errors due to these differences were observed only rarely with trimethoprim
      sulfamethoxazole (n = 5), cefaclor (n = 8), and cefamandole (n = 3). The
      interobserver variability in MIC determinations was found to be greater when LHB
      was used than when HTM was used. There was no difference in intraobserver
      variability between the two medium formulations. beta-Lactamase-positive isolates
      developed false resistance to amoxicillin-clavulanate 2 weeks after microdilution
      panels of both types of medium were stored at -20 degrees C but not when panels
      were stored at -70 degrees C. In conclusion, this study supports the use of HTM
      rather than LHB for sensitivity testing of H. influenzae because of its lower
      rate of interobserver variability and its ability to support the growth of these
      organisms, which is comparable to that of LHB.

PMID- 1400991
TI  - Development of oligonucleotide primers and probes against structural and
      regulatory genes of human immunodeficiency virus type 1 (HIV-1) and their use for
      amplification of HIV-1 provirus by using polymerase chain reaction.
AB  - The polymerase chain reaction is a powerful technique for amplifying a few copies
      of double-stranded genetic material to millions of copies in a few hours. The
      sensitivity and specificity of the polymerase chain reaction technique depend to
      some extent on the nucleotide sequences of the oligonucleotide primer pair used
      in the amplification. We report new oligonucleotide primers and probes which can
      be used for the amplification and detection of human immunodeficiency virus type
      1 provirus sequences of not only structural but also regulatory genes. These
      primers are very sensitive and specific and can be used for the detection of
      African and North American strains of human immunodeficiency virus type 1.

PMID- 1400993
TI  - Neisseria spp. and AIDS.
AB  - Neisseria meningitidis from various serogroups and two commensal neisseriae (N.
      sicca and N. perflava) were isolated from 15 patients at various stages of human
      immunodeficiency virus infection in this clinical and bacteriological study. The
      cases were grouped into the following three classes: (i) infections with an N.
      meningitidis strain of a serogroup known to be pathogenic (A, B, or C) and
      apparently independent of the human immunodeficiency virus infection, (ii)
      infections with a N. meningitidis strain of a serogroup which is normally either
      commensal or poorly pathogenic (serogroups Y, X, Z, and Z,29E), (iii) pulmonary
      and disseminated infections occurring in the course of the clinical evolutionary
      stage of AIDS, in two cases of which commensal neisseriae (N. sicca and N.
      perflava) were isolated from blood cultures.

PMID- 1400994
TI  - Development and testing of a nonradioactive DNA oligonucleotide probe that is
      specific for Vibrio cholerae cholera toxin.
AB  - An alkaline phosphatase-labeled oligonucleotide DNA probe (CTAP) that was
      specific for the cholera toxin gene (ctxA) was identified. All cholera toxin
      producing strains of Vibrio cholerae, regardless of serotype, hybridized with the
      CTAP probe, while nontoxigenic strains from either environmental sources or from
      deletion or substitution mutations did not hybridize. Unlike the whole-gene
      probes for either ctxA or for the heat-labile toxin or Escherichia coli (eltA),
      this 23-base sequence did not hybridize with E. coli or with vibrios other than
      V. cholerae that produce related toxins. By using CTAP to identify colonies grown
      on nonselective medium, V. cholerae was enumerated at concentrations of 10(3) to
      10(7)/g from stool samples of volunteers who had ingested V. cholerae O1 strain
      569B. CTAP provides a specific and sensitive tool for diagnosis and environmental
      monitoring of cholera toxin-producing V. cholerae.

PMID- 1400996
TI  - Endocarditis caused by Blastoschizomyces capitatus and taxonomic review of the
      genus.
AB  - Blastoschizomyces capitatus Salkin, Gordon, Samsonoff et Rieder was found to be
      the etiologic agent of endocarditis in a patient with a prosthetic mitral valve.
      Cultures inoculated with peripheral blood and portions of the valve yielded B.
      capitatus. Examination of stained tissue sections revealed the presence of fungal
      filaments morphologically consistent with this organism. The salient
      characteristics of B. capitatus and the factors contributing to its recognition
      as a distinct taxon are described.

PMID- 1400995
TI  - Serological detection of Helicobacter pylori by a flow microsphere
      immunofluorescence assay.
AB  - A flow cytometric immunofluorescence assay (FMIA) for the detection of
      immunoglobulin G antibodies to Helicobacter pylori was developed. A
      multicomponent antigen was prepared and used to coat carboxylated polystyrene
      microspheres for reaction with patient sera followed by fluorescein
      isothiocyanate-labelled goat anti-human immunoglobulin G. The reacted
      microspheres were collected with a flow cytometer, and fluorescence was
      quantitated relative to the cutoff value provided by pooled sera from patients in
      whom H. pylori could not be demonstrated by culture or histology. Serum samples
      from 28 H. pylori-positive patients and 27 H. pylori-negative patients were
      tested by FMIA. Additionally, an in-house enzyme-linked immunosorbent assay
      (ELISA) employing the same antigen preparation and a commercially available ELISA
      were used to assay the patient population. Both the FMIA and in-house ELISA were
      100% sensitive and 89% specific with positive and negative predictive values of
      90 and 100% and no equivocal results. The commercial ELISA was 96% sensitive and
      89% specific with positive and negative predictive values of 90 and 96% and five
      equivocal results. FMIA provides a rapid, inexpensive, and easily performed means
      for serodiagnosis of H. pylori.

PMID- 1400997
TI  - Enzymatically active Peptostreptococcus magnus: association with site of
      infection.
AB  - Fifty-four strains of Peptostreptococcus magnus (11 were recovered from abdominal
      infections, 18 were from nonpuerperal breast abscesses, and 21 were from diabetic
      foot infections; the type strain and three other strains were from the American
      Type Culture Collection, Rockville, Md.) and the type strain of
      Peptostreptococcus micros were tested for their ability to produce various
      enzymes, including catalase, hippurate hydrolase, serine dehydratase, threonine
      dehydratase, collagenase, gelatinase, alkaline phosphatase, and esterase C4. The
      data were analyzed by cluster analysis. The results showed that all but one
      strain could be assigned to either of two distinct, valid clusters. The first
      cluster of 11 strains was composed of strains that were relatively inactive,
      having produced one or two of the eight strain-dependent enzymes. The second was
      a large cluster of strains (n = 43) that were considerably more active, all
      having produced at least three enzymes; the vast majority of strains (89%)
      produced four or more enzymes. The unclustered strain produced one enzyme that
      was different from that produced by the strains in the first cluster. The chi 2
      test of homogeneity applied to the clustering solution indicated that greater
      enzyme activity was significantly associated with the site of infection (P less
      than 0.001). The more enzymatically active P. magnus strains were recovered
      significantly more often from nonpuerperal breast abscesses and diabetic foot
      infections than they were from abdominal infections. These results may provide
      insight into the nature of certain polymicrobial soft tissue infections and
      suggest that (i) P. magnus may participate more in nonpuerperal breast and
      diabetic foot infections than in abdominal infections and that (ii)
      peptostreptococcal production of proteolytic enzymes may have an important
      adjunctive effect on the pathogenesis of certain soft tissue infections.

PMID- 1400998
TI  - Outbreak of recurrent abdominal cramps associated with Arcobacter butzleri in an
      Italian school.
AB  - In the autumn of 1983, an outbreak of recurrent abdominal cramps occurred in a
      nursery and primary school in the Rovigo area in Italy. None of the 10 affected
      children had diarrhea. An atypical Campylobacter-like organism was isolated from
      feces in all cases. Conventional enteropathogens were searched for but not
      detected. The Campylobacter-like organism was identified as Arcobacter butzleri
      by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell
      proteins and cellular fatty acid analysis. Its identity was confirmed by DNA-DNA
      hybridizations versus Arcobacter reference strains. All of the preserved outbreak
      strains have identical protein profiles and phenotypic characteristics and belong
      to serogroup 1 of the Lior serotyping scheme on the basis of slide agglutination
      of crude and absorbed antisera of A. butzleri reference strains versus heat
      labile antigens of live bacteria. These data point to an epidemiological
      relationship. The successive timing of the cases suggests person-to-person
      transmission.

PMID- 1400999
TI  - Highly sensitive immunoassay for direct diagnosis of viral hemorrhagic septicemia
      which uses antinucleocapsid monoclonal antibodies.
AB  - An antigen capture enzyme-linked immunosorbent assay (ELISA) based on the
      detection of the viral nucleocapsid (anti-N system) was developed for the
      diagnosis of viral hemorrhagic septicemia. Four monoclonal antibodies directed
      against the viral nucleocapsid were produced; they all recognized the four viral
      hemorrhagic septicemia virus (VHSV) serotypes. Three of these monoclonal
      antibodies were used in a new antigen capture ELISA. The efficiency of the anti-N
      system in detecting purified and crude viruses as well as the virus in infected
      organ extracts and infected blood was compared with that of a recently described
      antigen capture ELISA based on the detection of viral envelope glycoprotein Gp
      (anti-G system). For the detection of purified virus, the anti-N system was found
      to be as sensitive as the anti-G system (detection limit, 1 ng of total viral
      protein per ml), but the anti-N system was much more sensitive than the anti-G
      system for the detection of crude VHSV I (detection limits, 1 x 10(4) PFU/ml
      versus 5 x 10(5) PFU/ml). In organ extracts, VHSV I could be detected by both
      systems 3 days postinfection. The signal for the assay of VHSV I in blood 24 h
      postinfection was higher with the anti-N system than the anti-G system.
      Furthermore, VHSV I could be detected in 80% of the brain samples of surviving
      trout by the anti-N system and also by the anti-G system, but with a lower
      signal. In conclusion, we have developed a highly sensitive immunoassay for VHSV
      I that is more rapid and easier to perform than the currently used plaque assay.

PMID- 1401000
TI  - Blood spot screening and confirmatory tests for syphilis antibody.
AB  - We developed a blood spot test for syphilis antibody using enzyme-linked
      immunosorbent assay (ELISA) technology. Dried blood was eluted by buffered saline
      or, for a supplementary confirmatory test, by treponemal-antibody test diluent.
      Eluates were diluted in an absorption buffer (Calypte Biomedical, Berkeley,
      Calif.) and added to plate wells coated with cardiolipin antigen (ADI
      Diagnostics, Toronto, Ontario, Canada). The wells were washed and treated
      sequentially with an immunoglobulin G conjugate, buffer washes, and enzyme
      substrate. Substrate conversion was measured photometrically, and specimen
      reactivity was determined by reference to nonreactive controls. The optimum test
      protocol was established by tests of serum and plasma. The serum ELISA
      specificity with normal specimens was 98.9%. The sensitivity with sera from
      patients with undefined syphilis was 97.4%, that with sera from patients with
      documented primary and secondary disease was 100%, and that with sera from
      patients with early and late latent disease was 95.7%. The specificity of the
      spot test with donor blood was 94.2%, and its specificity with newborn blood was
      94.9%. The sensitivity with 25 spots spiked with reactive sera was 96%. The
      seroprevalence rates for parturient women in one hospital were 6.01% according to
      spot tests of sera from 599 newborns and 6.81% according to Rapid Plasma Reagin
      tests of 499 maternal serum specimens. Seventy percent of infants born to 50
      seropositive women were reactive by either the newborn spot or the Rapid Plasma
      Reagin serum test. The results show that blood spots may be used in
      seroprevalence or serodiagnostic studies, especially to identify women who are
      infected or to identify possible cases of congenital infection. The test provides
      for studies of children and adults when routine venipuncture and serum handling
      and storage are problematic.

PMID- 1401001
TI  - Antimicrobial susceptibility patterns of common and unusual species of
      enterococci causing infections in the United States. Enterococcal Study Group.
AB  - We collected 705 isolates of enterococci (1 per patient) from cultures of a
      variety of anatomic sites from patients at eight tertiary-care hospitals in six
      geographic regions of the United States. A total of 632 (90%) Enterococcus
      faecalis, 58 (8%) E. faecium, 5 E. gallinarum, 4 E. avium, 3 E. casseliflavus, 1
      E. raffinosus, and 1 E. hirae isolate and 1 biochemical variant of E. faecalis
      were identified; 606 (86%) of these isolates were associated with clinical
      infections. The most common sites of isolation were the urinary tract (402
      [57%]), nonsurgical wounds (94 [13%]), the bloodstream (74 [10%]), and surgical
      wounds (62 [9%]). High-level resistance to gentamicin or streptomycin or both was
      detected in 265 (38%) of the isolates. We identified two E. faecalis isolates
      resistant to vancomycin (MICs, 32 and 128 micrograms/ml) and 11 beta-lactamase
      producing E. faecalis isolates. E. faecium isolates were significantly more
      resistant than E. faecalis isolates to penicillin, ampicillin, piperacillin,
      imipenem, and ciprofloxacin (P less than 0.001). The MICs for the 15 non-E.
      faecalis, non-E. faecium enterococci indicated variable resistance to
      ciprofloxacin and the penicillins. Antimicrobial susceptibility patterns vary
      among species of enterococci, and these organisms, while commonly resistant to
      high-level aminoglycosides, can also acquire resistance to vancomycin or the
      ability to produce beta-lactamase. Because of these diverse antimicrobial
      resistance mechanisms, successful treatment and control of enterococcal
      infections with current antimicrobial agents are becoming increasingly difficult.

PMID- 1401002
TI  - Early detection of antibody to human immunodeficiency virus type 1 by using an
      antigen conjugate immunoassay correlates with the presence of immunoglobulin M
      antibody.
AB  - Sequential plasma samples obtained from 16 individuals who seroconverted were
      tested for the presence of antibody to human immunodeficiency virus type 1 (HIV
      1) by an antigen conjugate enzyme immunoassay (EIA) and a conventional antibody
      conjugate assay. In 11 of these individuals, the antigen conjugate assay detected
      antibody to HIV-1 2 to 11 days (mean, 5.5 days) earlier than the antibody
      conjugate assay. In 11 individuals, HIV-1 p24 antigen was detected a median of
      6.5 days (range, 3 to 14 days) prior to positivity by the antigen conjugate EIA.
      Using class-specific probes, we determined the profiles of immunoglobulin M
      (IgM), IgG, and IgA antibodies for each individual and correlated these profiles
      with the EIA signals from both assays. In general, the appearance of IgM
      exhibited a peak at about 1 week postseroconversion, which was followed by
      gradually declining levels. Absorbance levels for IgG antibody, however, rose
      steadily and reached a plateau after 3 to 5 weeks. The levels of IgA were
      generally low and variable. In contrast to the progressive increase in EIA
      absorbance observed by the antibody conjugate assay, the antigen conjugate assay
      displayed a rapid early rise in absorbance which generally coincided with the
      transient expression of IgM antibody. The subsequent gradual increase coincided
      with rising levels of IgG. Because the configuration of the antigen conjugate EIA
      allows for an increased sensitivity for IgM compared with that for other classes
      of immunoglobulins, these results suggest that earlier detection of antibody to
      HIV-1 is due to the detection of IgM antibody during the early phase of
      seroconversion.

PMID- 1401003
TI  - Phenotypic variation of Staphylococcus epidermidis isolated from a patient with
      native valve endocarditis.
AB  - Two colonial variants of Staphylococcus epidermidis were isolated from the
      valvular tissue of a patient with native valve endocarditis. In addition to
      differing in colonial morphology, the two variants differed in hemolysis on blood
      containing media, in adherence capacity, and in the expression of certain
      enzymes. Under suitable conditions, both variants were themselves capable of
      phenotypic variation, although they differed in the rate at which variants were
      generated. The variants yielded identical profiles on restriction endonuclease
      analysis of plasmid DNA and pulsed-field gel electrophoresis of whole-cell DNA.
      This report suggests a possible role for phenotypic variation in coagulase
      negative staphylococcal virulence. Congo red agar would be an excellent medium
      for studying the contribution of variation to the virulence of these organisms.

PMID- 1401004
TI  - M protein gene typing of Streptococcus pyogenes by nonradioactively labeled
      oligonucleotide probes.
AB  - A new approach for the typing of Streptococcus pyogenes is described.
      Oligonucleotide probes of 30 nucleotides in length were derived from currently
      known sequences of the N-terminal regions of M protein genes (emm genes). The
      oligonucleotides were labeled with digoxigenin-dUTP and hybridized to dot-blotted
      genomic DNA from 116 group A streptococcal strains of serotypes M-1, M-2, M-3, M
      5, M-6, M-12, M-18, M-19, M-24, and M-49. Hybridization reactions were visualized
      with a chemiluminescent substrate. In comparison with conventional serological
      typing of expressed M proteins, the binding of the probes to the corresponding
      emm genes exhibited 100% sensitivity and specificity. The results emphasize the
      high degree of type-specific conservation of the N-terminal regions of emm genes
      from reference strains and epidemiologically unrelated U.S. and European clinical
      isolates. The existence of two distinct genetic subgroups among eight
      investigated M-49 strains was unequivocally shown by hybridization assays and
      further confirmed by nucleotide sequence data obtained from four selected M-49
      strains. Because oligonucleotide probes are relatively easy to prepare, easy to
      handle, and known to give consistent interlaboratory results, the "oligotyping"
      technique appears to offer potential advantages over conventional serological
      typing methods.

PMID- 1401005
TI  - Legionella lansingensis sp. nov. isolated from a patient with pneumonia and
      underlying chronic lymphocytic leukemia.
AB  - A Legionella-like organism, strain 1677-MI-H, was isolated from the bronchoscopy
      washings of a patient with pneumonia who had a 2-year history of progressive,
      chronic lymphocytic leukemia. The growth characteristics, cellular fatty acids,
      and ubiquinone content of the isolate were consistent with those for Legionella
      spp. The isolate was serologically distinct in the slide agglutination test with
      absorbed antisera. DNA hybridization studies showed that strain 1677-MI-H (ATCC
      49751) represents a new Legionella species which is named Legionella
      lansingensis.

PMID- 1401006
TI  - High-performance liquid chromatography patterns of Mycobacterium gordonae mycolic
      acids.
AB  - An important class of fatty acids contained in the cell envelopes of
      Mycobacterium organisms is the group of high-molecular-weight, long-chain, alpha
      branched, beta-hydroxylated mycolic acids. By using standard saponification
      techniques and derivatization of the acids to their p-bromophenacyl esters, it is
      possible to differentiate them by high-performance liquid chromatography. Mycolic
      acid chromatograms of 63 clinical isolates of Mycobacterium gordonae were
      compared with conventional biochemical methods for identification. The data show
      two distinct pattern types for this species, only one of which has been
      elaborated in the literature by using this protocol. Laboratory workers who
      intend to use this method as a clinical tool need to be aware that these two
      pattern types exist.

PMID- 1401007
TI  - Restriction endonuclease analysis and ribotyping differentiate genital and
      nongenital strains of Bacteroides ureolyticus.
AB  - Thirty-three clinical isolates from male nongonococcal urethritis and 28 isolates
      from soft tissue infections and ulcers were identified as Bacteroides ureolyticus
      by conventional bacteriological tests and were compared with five reference
      strains of the species. Whole-cell proteins from these clinical isolates and the
      reference strains were separated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). The majority of the strains from the two sources
      could be divided into five different groups, named phenons I to V; phenons I to
      IV have been described previously by others, while phenon V has been described
      recently by us. Digestion of chromosomal DNA from 16 of the clinical isolates
      (including strains representative of each of the five SDS-PAGE phenons) and the
      five reference strains was attempted with restriction endonucleases EcoRI, PstI,
      SmaI, and HindIII. After electrophoresis in agarose gels, good digestion was
      observed with HindIII only, and 12 different banding patterns (restriction
      endonuclease analysis [REA] profiles) were obtained for the 19 strains digested;
      one nongonococcal urethritis isolate and one reference strain did not show any
      digestion. From the agarose gels, HindIII-digested fragments of DNA were
      transferred to nylon membranes by use of vacuum blotting and subjected to
      hybridization with 32P-labelled 16S-23S rRNA from Escherichia coli. The resultant
      pattern of bands (ribotypes), which depends on the restriction fragment length
      polymorphisms in the rRNA genes, was used as a measure of genomic variation
      within the species. In total, 13 different ribotypes were obtained for the 19
      strains. For some strains, good correlation was achieved among the SDS-PAGE
      phenons, REA profiles, and ribotypes. However, for others, REA analysis and
      ribotyping were able to discriminate between strains which shared the same SDS
      PAGE phenon. Interestingly, these two techniques of DNA characterization were
      able to differentiate between isolates from the genital tract and those
      associated with soft tissue infections and ulcers.

PMID- 1401008
TI  - Detection of lipoarabinomannan as a diagnostic test for tuberculosis.
AB  - A coagglutination technique was established for the detection of
      lipoarabinomannan of Mycobacterium tuberculosis in human serum samples and
      evaluated for its utility in the diagnosis of tuberculosis at the Instituto
      Nacional de Enfermedades Respiratorias in Mexico City. The test had a sensitivity
      of 88% in patients with sputum-smear-positive active pulmonary tuberculosis. The
      sensitivity in patients with active pulmonary tuberculosis negative for acid-fast
      bacilli in sputum was 67%. Less favorable results were obtained for patients with
      AIDS and tuberculosis, with a sensitivity of 57%. The specificity in control
      patients with lung diseases different from tuberculosis and in healthy subjects
      was 100%. The positive predictive value was 100%, and the negative predictive
      value for patients with sputum-positive active pulmonary tuberculosis was 97%.
      The results of this study suggest that the detection of lipoarabinomannan is an
      accurate test for the diagnosis of pulmonary tuberculosis.

PMID- 1401009
TI  - Antigenic and molecular characterization of bat rabies virus in Europe.
AB  - The predominant role of Eptesicus serotinus in the epizootic of bat rabies in
      Europe was further outlined by the first isolation of the rabies virus from this
      species in France. The distribution of the virus was studied in naturally
      infected E. serotinus bats at the time of death and suggested that the papillae
      of the tongue and the respiratory mucosa may play a role in virus production and
      excretion. The analysis of 501 French rabies virus isolates from various animal
      species by antinucleocapsid monoclonal antibodies indicated that transmission of
      the disease from bats to terrestrial animals is unlikely. The antigenic profile
      of two isolates from French bats corresponded to that of European bat lyssavirus
      type 1 (EBL1). Comparisons of 12 different isolates from bats with
      antinucleocapsid and antiglycoprotein monoclonal antibodies and by direct
      sequencing of the polymerase chain reaction amplification product of the N gene
      indicated that EBL1, EBL2, Duvenhage virus (serotype 4 of lyssavirus), and the
      European fox rabies virus (serotype 1) are phylogenetically distant. They formed
      four tight genetic clusters named genotypes. EBL1 was shown to be antigenically
      and genetically more closely related to Duvenhage virus than to EBL2. We propose
      that EBL1 and EBL2 constitute two distinct genotypes which further serologic
      characterization will probably classify as new serotypes. We also report a simple
      method for the rapid characterization of EBL based on the digestion of the
      polymerase chain reaction product of the N gene by three restriction
      endonucleases.

PMID- 1401011
TI  - Biochemical and antigenic properties of Streptococcus bovis isolated from
      pigeons.
AB  - Biochemical and serological properties of 60 strains of Streptococcus bovis
      isolated from healthy pigeons and from pigeons that died from S. bovis septicemia
      were determined. On the basis of the hemolysis of bovine erythrocytes, the
      production of polysaccharides on saccharose-containing media, and the
      fermentation of mannitol, inulin, trehalose, and L-arabinose, the isolates were
      classified in five biotypes and two subbiotypes. Slide agglutination and
      microagglutination tests using monospecific rabbit antisera allowed the
      classification of all isolates in five serotypes.

PMID- 1401010
TI  - Identification of Mycobacterium tuberculosis and Mycobacterium avium-M.
      intracellulare directly from primary BACTEC cultures by using acridinium-ester
      labeled DNA probes.
AB  - Identification of members of the Mycobacterium tuberculosis complex and the M.
      avium-M. intracellulare complex (MAC) directly from primary BACTEC cultures was
      evaluated by using acridinium-ester-labeled DNA probes (AccuProbe; GenProbe,
      Inc., San Diego, Calif.). In preliminary experiments, blood present in samples
      was found to interfere with the assay because of nonspecific chemiluminescence,
      which was measured in relative light units (RLUs). There was a direct
      relationship between the age of the culture and the number of nonspecific RLUs. A
      protocol using 1% sodium dodecyl sulfate-5 mM EDTA to treat BACTEC broth cultures
      which, with specimens containing blood, gave on the average a ninefold reduction
      in nonspecific chemiluminescence was developed. By using this treatment protocol,
      120 specimens were tested directly from BACTEC broth cultures with an AccuProbe
      for the M. tuberculosis complex and/or the MAC. In order to establish the
      background of the specimen, the patient sample was assayed without probe. The
      criteria for the inclusion of BACTEC cultures in the evaluation were a growth
      index of greater than or equal to 100 and a positive smear for acid-fast bacilli
      directly from the BACTEC broth. For the 120 cultures tested, if a hybridization
      result of greater than or equal to 30,000 RLUs was considered positive, the
      sensitivities for detecting the M. tuberculosis complex and the MAC were 47 and
      90%, respectively, with a specificity of 100% for both. However, if a ratio of
      the RLUs obtained with the MAC or the M. tuberculosis complex probe to those
      obtained with the specimen background of >/= 20 was considered positive, this
      gave 77% sensitivity and 100% specificity for BACTEC cultures containing M.
      tuberculosis complex isolates and 96% sensitivity and 100% specificity for those
      growing MAC isolates.

PMID- 1401012
TI  - Evidence that Lo's mycoplasma (Mycoplasma fermentans incognitus) is not a unique
      strain among Mycoplasma fermentans strains.
AB  - Mycoplasma fermentans incognitus has attracted much interest either as a cofactor
      for the progression of AIDS or as a pathogenic agent in non-AIDS-related diseases
      (S.-C. Lo, M. S. Dawson, P. B. Newton III, M. A. Sonoda, J. W.-K. Shih, W. F.
      Engler, R. Y.-H. Wang, and D. J. Wear, Am. J. Trop. Med. Hyg. 41:364-376, 1989;
      S.-C. Lo, M. S. Dawson, M. Wong, P. B. Newton III, M. A. Sonoda, W. F. Engler,
      R.Y.-H Wang, J. W.-K. Shih, H. J. Alter, and D. J. Wear, Am. J. Trop. Med. Hyg.
      41:601-616, 1989; S.-C. Lo, J.W.-K. Shih, N.-Y. Yang, C.-Y. Ou, and R. Y.-H.
      Wang, Am. J. Trop. Med. Hyg. 40:213-226, 1989). In the present study, the genetic
      and serologic properties of the incognitus strain and other M. fermentans strains
      were compared. Furthermore, the replication of human immunodeficiency virus type
      1 (HIV-1), determined by reverse transcriptase activity and HIV-1 p24 antigen
      level, in peripheral blood mononuclear cells was evaluated after stimulation with
      mycoplasma cell lysates. The psb-2.2 viruslike infectious agent DNA probe, used
      to identify the incognitus strain in the tissues of AIDS and non-AIDS patients by
      Lo et al. (Am. J. Trop. Med. Hyg. 41:364-376 and 40:213-226, 1989), showed
      reaction patterns similar to those of two M. fermentans strains isolated from
      cell cultures but not to that of the type strain PG18. Restriction enzyme
      patterns of the incognitus strain with EcoRI and HindIII were also similar to
      those of M. fermentans strains isolated from cell cultures. There were no
      remarkable differences in the immunoblot profiles between the incognitus strain
      and the other M. fermentans strains. These results suggest that the incognitus
      strain is not a unique strain among M. fermentans strains. Further, cell lysates
      of each M. fermentans strain could also enhance the replication of HIV-1 to a
      level similar to that of the incognitus strain as determined by the reverse
      transcriptase activity and the amount of the p24 antigen.

PMID- 1401013
TI  - Acanthamoeba keratitis: synergy between amebic and bacterial cocontaminants in
      contact lens care systems as a prelude to infection.
AB  - We encountered a patient with Acanthamoeba keratitis whose contact lens care
      solution contained numerous trophozoites and cysts admixed with Xanthomonas
      maltophilia organisms, many of which were adherent to the trophozoite surface and
      internalized within endocytic vacuoles. Because of this finding, we investigated
      the role of bacterial cocontaminants in contact lens care systems as substrates
      for the growth of Acanthamoeba spp. Individual cocultivation of Acanthamoeba
      castellanii and A. polyphaga with X. maltophilia, Flavobacterium breve, and
      Pseudomonas paucimobilis showed better enhancement (1.5x) of ameba growth after
      96 h than that obtained in the presence of Staphylococcus aureus, S. epidermidis,
      and Escherichia coli, the standard cocultivation species used for isolation of
      amebae from clinical specimens. Our data suggest that contamination of contact
      lens care systems with Acanthamoeba spp. and a bacterial species capable of
      supporting amebic growth may be the first step in the pathogenesis of ameba
      induced keratitis by the provision of large inocula of amebae.

PMID- 1401014
TI  - Enzyme immunoassay for Q fever: comparison with complement fixation and
      immunofluorescence tests and dot immunoblotting.
AB  - Enzyme-linked immunosorbent assays (ELISA) for the detection of specific
      immunoglobulin G (IgG) and IgM antibodies were developed by using purified
      Coxiella burnetii cells. Variables, including type of microtiter plate, blocking
      agent, incubation conditions, antigen stability, and substrate type, were
      examined to achieve optimal ELISA performance. The reliabilities of the assay
      systems were compared with those of complement fixation (CF) and enhanced
      immunofluorescence (EIF) tests with 600 human serum samples from defined clinical
      cases of Q fever, routine samples, and serum specimens from farmers. ELISA and
      EIF test results agreed in all cases. Dot immunoblotting was also used to test
      some of these sera and gave a rapid, qualitative result, which agreed with ELISA
      and EIF test results in all cases. No instances were found in which both ELISA
      and EIF test results were negative and the CF test results was positive. However
      approximately 5% of the sera were positive by ELISA and the EIF test while the CF
      test result was either negative or unreadable because of serum anticomplementary
      activity. We conclude that dot immunoblotting is a useful screening test, whereas
      ELISA and the EIF test are both rapid and sensitive tests when used for the
      serodiagnosis of Q fever and should be considered to be replacements for the CF
      test.

PMID- 1401016
TI  - Detection of Coxiella burnetti by DNA amplification using polymerase chain
      reaction.
AB  - The polymerase chain reaction (PCR) was used for the detection of Coxiella
      burnetti, an obligate intracellular bacterium and the etiologic agent of Q fever.
      A pair of primers derived from the C. burnetii superoxide dismutase gene served
      to amplify a targeted 257-bp fragment of genomic DNA. These primers were chosen
      on the basis of GenBank analysis, G + C ratio, and absence of secondary
      structure. This technique allowed the detection of as few as 10 C. burnetii
      organisms. C. burnetti was detected in tissue culture and in specimens from
      patients (heart valves). In all, 8 reference isolates and 22 new isolates of C.
      burnetii from France were successfully amplified. No amplification products were
      found when PCR was performed with 25 bacterial species that had been isolated in
      a clinical laboratory from patients with clinically similar infections.
      Amplification products of C. burnetii were confirmed by restriction enzyme
      digestion and dot blot hybridization. The method used here, a combination of PCR
      and restriction analysis, is a faster and more sensitive assay for C. burnetii
      than standard culture techniques.

PMID- 1401015
TI  - Surface immunofluorescence assay for diagnosis of Lyme disease.
AB  - A surface immunofluorescence assay (SIFA) was analyzed and compared with a
      conventional indirect immunofluorescence assay (IFA) and whole-cell enzyme-linked
      immunosorbent assay (ELISA) for detecting immunoglobulin G (IgG) antibodies to
      Borrelia burgdorferi in sera from patients with Lyme disease. Fifty-five patients
      with syphilis and 33 patients with rheumatoid arthritis were used as disease
      controls. The sensitivity of the SIFA was low during the acute phase of Lyme
      disease (sera from seven of nine patients presenting with erythema chronicum
      migrans were negative during the first 2 months of illness); later,
      seroconversion was observed in all patients at various times during
      convalescence. Sera from five patients with complicated Lyme disease were
      strongly positive. SIFA was found to be highly specific, since sera from all
      patients with secondary or latent syphilis and patients with rheumatoid arthritis
      did not react in the test. Strong cross-reactivity occurred when these sera were
      tested in conventional IFA and ELISA; sera from 38 (69%) patients with syphilis
      were positive by IFA and sera from 51 (93%) patients were positive by ELISA,
      whereas 7 (21%) and 12 (36%) of the serum samples from patients with rheumatoid
      arthritis were positive by IFA and ELISA, respectively. Immunoblot analysis of
      SIFA-positive sera showed that the 31- and 34-kDa outer surface proteins
      (proteins A and B, respectively) of B. burgdorferi were the major reactive
      antigens involved in the test. The results support a role for SIFA in the
      investigation of complicated Lyme disease as well as in the differentiation of
      Lyme disease from other diseases associated with B. burgdorferi cross-reactive
      antibodies.

PMID- 1401017
TI  - Murine Pneumocystis carinii adherence to vertical monolayers of cultured mink
      lung cells (MiCl1).
AB  - We describe a method for adherence and culture of murine Pneumocystis carinii in
      mink lung cells (MiCl1) grown on vertical supports. The vertical cultures were
      infected with P. carinii; the surrounding medium and inoculum were stirred to
      ensure circulation and contact with MiCl1 cells. When compared with conventional
      horizontal culture, the vertical method offers a more suitable system for
      assessing P. carinii adherence. This approach has proved suitable for
      quantitative evaluation of P. carinii adherence to MiCl1 cells in the presence of
      inhibitors.

PMID- 1401018
TI  - Endocarditis caused by a group B Streptococcus strain, type III, in a
      nonencapsulated phase.
AB  - A nontypeable blood isolate of group B streptococci (GBS) from a patient with
      endocarditis is suggested to be the nonencapsulated phase of a GBS strain, type
      III. From the original high-density isolate, a low-density, encapsulated phase
      was selected by Percoll gradient centrifugation. This phenomenon should be
      considered before a GBS strain is classified as truly nontypeable.

PMID- 1401019
TI  - Bordetella bronchiseptica pneumonia and bacteremia following bone marrow
      transplantation.
AB  - Bordetella bronchiseptica is a frequent cause of respiratory infections in
      animals but rarely causes disease in humans. We describe a patient with B.
      bronchiseptica pneumonia and bacteremia that developed following bone marrow
      transplantation. B. bronchiseptica infection persisted despite antimicrobial
      therapy and may have progressed because of the combined effects of the patient's
      underlying immunosuppression and the antimicrobial antagonism between doxycycline
      and ciprofloxacin.

PMID- 1401020
TI  - Evaluation of nonradioactive DNA probes for identification of mycobacteria.
AB  - Commercial chemiluminescent DNA probes (Accuprobe; Gen-Probe, San Diego, Calif.)
      for the identification of Mycobacterium tuberculosis (MTB) complex, M. avium
      complex (MAC), M. gordonae, and M. kansasii were evaluated with 134 clinical
      isolates. These included 36 MTB complex, 40 MAC, 27 M. gordonae, 9 M. kansasii,
      and 22 Mycobacterium spp. The specificity was 100% for the four probes. The
      sensitivity was 100% for the MTB complex and M. gordonae probes and 95.2% for the
      MAC probe. Five of the nine M. kansasii isolates tested were not detected with
      the probe.

PMID- 1401021
TI  - Paecilomyces lilacinus catheter-related fungemia in an immunocompromised
      pediatric patient.
AB  - Paecilomyces lilacinus catheter-related fungemia in an immunocompromised child is
      reported. The presence of a central venous catheter and the patient's
      immunocompromised status were felt to be predisposing factors for this unusual
      infection. To our knowledge, this is the first description of P. lilacinus
      catheter-related fungemia, and our patient may be the youngest reported patient
      with this mycosis who was cured.

PMID- 1401022
TI  - Detection and identification of Yersinia pseudotuberculosis and pathogenic
      Yersinia enterocolitica by an improved polymerase chain reaction method.
AB  - We developed a polymerase chain reaction method in order to detect and identify
      both Yersinia pseudotuberculosis and pathogenic Yersinia enterocolitica.
      Polymerase chain reaction was performed by using a mixture of primers against the
      inv gene from Y. pseudotuberculosis and the ail gene from pathogenic Y.
      enterocolitica. Further addition of primers against the plasmid-coded virF gene
      from Y. enterocolitica made it possible to detect a virulence-associated gene of
      both species at the same time. This method was proved to be an adequate and
      convenient procedure for routine detection and identification of these bacilli.

PMID- 1401023
TI  - Fatal pulmonary sporotrichosis caused by Sporothrix schenckii var. luriei in
      India.
AB  - The first case of fatal pulmonary sporotrichosis caused by Sporothrix schenckii
      var. luriei in a patient from the northwestern region of India is described. In
      the absence of cultures, the diagnosis was suspected by notation, in lung tissue,
      of large, thick-walled, hyaline fungal cells that divided internally by septation
      or a budding process. The thick-walled, internally septated cells often became
      muriform. The presence of an "eyeglass" configuration of incompletely separated
      cells characteristic of S. schenckii var. luriei in large numbers aided the
      diagnosis. The identity of the etiologic agent was confirmed by application of a
      fluorescent-antibody reagent specific for S. schenckii.

PMID- 1401024
TI  - Haemophilus influenzae is frequently detected with monoclonal antibody 8BD9 in
      sputum samples from patients with cystic fibrosis.
AB  - To determine the frequency of Haemophilus influenzae in sputum from patients with
      cystic fibrosis (CF), 477 sputum samples obtained from 86 CF patients were
      analyzed by standard culture and by the in situ immunoperoxidase staining
      technique with monoclonal antibody 8BD9. H. influenzae was isolated from 109
      sputum samples (23%) from 45 patients (52%) and detected by immunoperoxidase
      staining in 175 sputum samples (37%) obtained from 63 patients (73%). The results
      of this study demonstrate the frequent presence of H. influenzae in sputum
      samples from CF patients.

PMID- 1401025
TI  - Bilophila wadsworthia bacteremia in two patients with hepatic abscesses.
AB  - Bilophila wadsworthia, a recently described anaerobic gram-negative bacillus, was
      isolated from blood cultures of two patients with liver abscesses. These isolates
      exhibited the expected phenotypic characteristics, and identification was
      confirmed by cell wall fatty acid analysis by gas-liquid chromatography. This is
      the first documentation of bacteremia due to B. wadsworthia.

PMID- 1401026
TI  - Salmonella choleraesuis subsp. indica serovar bornheim causing urinary tract
      infection.
AB  - An unusual Salmonella species, S. choleraesuis subsp. indica serovar bornheim,
      was isolated from the urine of a patient with aplastic anemia, diabetes mellitus,
      and a healed urethral injury. An immune response to this isolate was demonstrated
      by whole-bacterial-cell agglutination.

PMID- 1401027
TI  - Osteomyelitis and intervertebral discitis caused by Pseudomonas pickettii.
AB  - Pseudomonas pickettii, a nonfermenting, gram-negative rod, is rarely pathogenic.
      Previous reports of infection with P. pickettii have largely involved direct
      contamination of supplies presumed to be sterile. We describe a case of vertebral
      osteomyelitis and intervertebral discitis caused by P. pickettii in a debilitated
      patient. The aggressive nature of this infection demonstrates that P. pickettii
      may be a more invasive organism than previously noted, particularly in hosts with
      weakened immunity secondary to underlying disease.

PMID- 1401029
TI  - Identification of some uncommon monounsaturated fatty acids of bacteria.
AB  - Location of the double-bond position of monounsaturated fatty acids of various
      bacteria was accomplished with combined gas chromatography-mass spectrometry
      analysis of dimethyl disulfide (DMDS) derivatives. The monoenoic fatty acids from
      whole cells were converted to methyl esters and then to DMDS adducts and analyzed
      by capillary gas chromatography-mass spectrometry. The mass spectra of DMDS
      adducts gave an easily recognizable molecular ion and two major diagnostic ions
      attributable to fragmentation between the two CH3S groups located at the original
      site of unsaturation. Twenty-one relatively novel monoenoic fatty acids were
      identified among the bacteria studied. All Flavobacterium species contained i17:1
      omega 8c, Bacillus alvei contained i16:1 omega 11c and i17:1 omega 12c, and
      Psychrobacter immobilis contained 12:1 omega 9c. Resolution of cis and trans
      isomers with capillary gas chromatography and subsequent mass spectrometry
      permitted positive identification of 16:1 omega 7c and 16:1 omega 7t in
      Arcobacter (Campylobacter) cryaerophila and 16:1 omega 9c and 16:1 omega 9t in
      Aerococcus viridans.

PMID- 1401028
TI  - Evaluation of an indirect immunofluorescence assay for confirmation of human
      immunodeficiency virus type 1 antibody in U.S. blood donor sera.
AB  - An indirect immunofluorescence assay (IFA) was evaluated as a confirmatory test
      for antibody to human immunodeficiency virus type 1 in U.S. blood donor sera
      previously found to be repeatedly reactive by enzyme immunoassay. IFA results
      were 100% concordant with a licensed Western blot (immunoblot) for 53 negative
      and 49 positive samples. Four samples which exhibited antibody to viral proteins
      from more than one gene, yet were indeterminate by Western blot by the
      manufacturer's criteria, were also reactive by IFA, whereas 49 additional
      indeterminate samples were IFA negative.

PMID- 1401031
TI  - Isolation of Kingella kingae from a corneal ulcer.
AB  - Kingella kingae was isolated from a corneal ulcer in an 11-month-old male. This
      organism has been previously reported from normally sterile sites, including
      sites of endophthalmitis, but this is the first time isolation from the cornea
      has been reported.

PMID- 1401030
TI  - Diagnosis of typhoid fever by detection of Salmonella typhi antigen in urine.
AB  - A monoclonal antibody specific for group D Salmonella antigen 9 was used in an
      indirect enzyme-linked immunosorbent assay (ELISA) for detecting the antigen in
      urine specimens collected from patients with clinical typhoid fever in Jakarta,
      Indonesia. The ELISA had a sensitivity of 95% in identifying patients in whom
      Salmonella typhi was isolated from hemocultures, 73% in patients in whom S. typhi
      was isolated from stool specimens, and 40% in patients in whom the organism was
      isolated from bone marrow cultures. Among patients in whom S. typhi was isolated
      from blood cultures, the ELISA had a sensitivity of 65% when a single urine
      specimen was examined and 95% when serially collected urine specimens were
      examined. A dot blot immunoassay performed on a nitrocellulose filter in parallel
      had a sensitivity of 85%, versus 83% for the plate ELISA in which S. typhi was
      isolated from blood, bone marrow, and/or stool specimens. Since S. typhi antigen
      is intermittently excreted in the urine of patients with typhoid fever, serially
      collected urine from patients with typhoid should be tested for antigen 9.

PMID- 1401033
TI  - Detection of circulating capsular polysaccharide antigen from Cryptococcus
      neoformans.

PMID- 1401032
TI  - Evaluation and optimization of a latex agglutination assay for detection of
      cholera toxin and Escherichia coli heat-labile toxin.
AB  - The effectiveness of a latex agglutination assay kit for the detection of
      Escherichia coli heat-labile toxin and cholera toxin was determined for the
      identification of natural isolates of the corresponding enteric pathogens in
      Southeast Asia. By selection of the appropriate culture media, the sensitivity of
      the assay was improved from 90.6% (for the detection of heat-labile toxin) and
      75% (for the detection of cholera toxin) to 100%, and the results were confirmed
      with bioassays and DNA hybridization assays for both clinical and environmental
      isolates.

PMID- 1401034
TI  - Rapid, low-technology, field- and laboratory-applicable immunodiagnosis of
      Schistosoma mansoni.

PMID- 1401035
TI  - Detection of Mycoplasma hyopneumoniae by using rRNA-oligodeoxynucleotide
      hybridization.

PMID- 1401037
TI  - Interpretation of the X-ray diffraction pattern from relaxed skeletal muscle and
      modelling of the thick filament structure.
AB  - The first part of this paper is devoted to the model-building studies of our high
      resolution meridional X-ray diffraction patterns (in the region from 1/500 to
      1/50 A-1) obtained from relaxed frog muscle. A one-dimensional model of thick
      filament was proposed which basically consists of two symmetrical arrays of 50
      crossbridge crown projections. In the proximate and central zones of the filament
      the crossbridge crowns are regularly shifted with a 429 A period and appear as
      triplets with a 130 A distance between crowns, while the crowns in the distal
      parts of filament are regularly ordered with a 143 A repeat. The centre-to-centre
      distance between regions with crossbridge perturbations is 7050 A. The length of
      each crown projection is about 125 A. The model includes also (1) C-protein
      component represented in each half of the filament by seven stripes of about 350
      A long and located 429 A apart, (2) a uniform density of filament backbone of
      about 1.5 micron length, and (3) 13 high density stripes in a central zone
      located with 223 A period. The final model explains very well the positions and
      intensities of the main meridional reflections. A three-dimensional model of
      crossbridge configuration is described in the second part of the work. The model
      was constructed by using the intensity profiles of the first six myosin layer
      lines of the X-ray pattern from stretched muscle and taking into account the
      crossbridge perturbations and the axial size of crossbridge crown obtained from
      the one-dimensional studies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401036
TI  - Molecular mechanism of troponin-C function.

PMID- 1401038
TI  - In situ compartmentation of creatine kinase in intact sarcomeric muscle: the acto
      myosin overlap zone as a molecular sieve.
AB  - Creatine kinase isoenzymes (CK = ATP: creatine N-phosphoryl transferase, EC
      2.7.3.2) were localized in situ in cryosections of intact sarcomeric muscle by
      immunocytochemical staining. Similar to cardiac muscle, spermatozoa and
      photoreceptor cells, mitochondrial-type CK (Mi-CK) localization in skeletal
      muscle was also restricted to mitochondria. Besides the well-documented
      localization of muscle-type (M-CK) at the M-line and at the sarcoplasmic
      reticulum, surprisingly, most of the sarcoplasmic M-CK was also highly
      compartmentalized and was mainly confined to the I-band. The localization of M-CK
      at the I-band coincided with that of adenylate kinase and aldolase. In intact
      muscle, the diffusion equilibrium decisively favours occupancy by all three
      enzymes of the I-band, with the acto-myosin overlap region of the A-band acting
      as a molecular sieve, excluding to a large extent all three enzymes from the acto
      myosin overlap region. This indicates that in intact muscle, this region of the A
      band may be less accessible in vivo to soluble, sarcoplasmic enzymes than thought
      before. If muscle were permeabilized by chemical skinning before fixation, I-band
      CK, as well as aldolase and adenylate kinase, were solubilized and disappeared
      from the myofibrils, but the fraction of M-CK which was specifically associated
      with the M-line remained bound to the myofibrils. Implications of these findings
      are discussed with respect to the functional coupling of I-band-CK with
      glycolysis, to the formation of large multienzyme complexes of glycolytic enzymes
      with CK and to the supply of energy for muscle contraction in general.

PMID- 1401039
TI  - Structural changes induced in scallop heavy meromyosin molecules by Ca2+ and ATP.
AB  - We have used physicochemical and ultrastructural methods to investigate the
      effects of Ca2+ and ATP on the structure of purified heavy meromyosin (HMM) from
      the striated adductor muscle of the scallop, a species with myosin-linked
      regulation. Using papain as a structural probe, we found that, in the presence of
      ATP, the head/tail junction was five times more susceptible to digestion at high
      levels of Ca2+ than at low levels. By HPLC gel filtration, two fractions of
      scallop HMM with different Stokes radii were detected in the presence of ATP at
      low Ca2+, while at high Ca2+ a single peak with the larger Stokes radius
      predominated. Electron microscopy of rotary-shadowed HMM suggested that molecules
      with the smaller Stokes radius had their heads bent back towards their tails,
      while those with the larger radius had heads pointing away from the tail. The
      number of molecules with their heads bent back decreased at high Ca2+ levels. The
      data also showed that in the absence of ATP or at high salt, HMM molecules
      behaved similarly to those in the presence of ATP at high Ca2+. These results
      suggest that scallop myosin heads can exist in two conformations (heads down
      towards the tail and heads up away from the tail) and that the equilibrium
      between these two conformations is altered by the concentrations of salt, ATP and
      Ca2+. However, the equilibrium between the two forms appears to be too slow to be
      involved in regulating contraction. The 'heads-down' configuration may instead be
      related to the inactive, folded (10S) form of scallop myosin and possibly
      involved in filament assembly during development.

PMID- 1401041
TI  - Effects of N-ethylmaleimide on the structure of skinned frog skeletal muscles.
AB  - The effects of N-ethylmaleimide (NEM) and other sulfhydryl modifiers on the
      structure of skinned frog skeletal muscles were studied using the X-ray
      diffraction technique. In sartorius muscle with full overlap between the thick
      and thin filaments, 0.1-1.0 mM NEM changed the intensity ratio of the (1,0) and
      (1,1) equatorial reflections from 4.35 to 0.72, and the (1,0) spacing of the
      hexagonal filament lattice from 40.4 to 41.4 nm. The axial X-ray diffraction
      pattern showed weak myosin layer-lines after the NEM treatment but enhancement of
      the actin layer-lines was not observed. In overstretched semitendinosus muscle,
      NEM did not affect the equatorial spacing but the myosin layer-lines were
      weakened. These results indicate that modification of myosin by NEM destroys the
      helical arrangement of myosin heads around the shaft of the thick filament and
      that when thin filaments are available, myosin heads move towards, and possibly
      bind to them. This binding is different from that in rigor since the 'ladder
      like' appearance of the higher actin layer-lines, which is typical of patterns
      from rigor muscles, was not observed. On removal of ATP after the NEM treatment,
      the diffraction pattern showed features characteristic of that from normal rigor
      muscles but no tension was produced. The pattern showed well-defined samplings on
      layer-lines in the small-angle region, indicating the presence of an extensive
      lattice order and exact axial alignment of the filaments. The first actin layer
      line did not show samplings from the superlattice of the thick filaments, which
      are observed on the myosin layer-lines in patterns from resting muscles.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1401042
TI  - Effects of ethylene glycol and calcium on the kinetics of contraction induced by
      photo-release of low concentrations of ATP in rat psoas muscle fibres.
AB  - To induce isometric contraction in the absence of Ca2+ (10 mM EGTA), low
      concentrations (130 microM) of ATP were photoreleased from caged ATP in skinned
      fibres from rat psoas muscle at 15-16 degrees C. The magnitude of contraction was
      independent of the concentration of EGTA (1-30 mM). Each isometric transient (i)
      was paired with another (s) obtained under the same conditions but with 0.4%
      muscle stretch to elevate the rigor force before photolysis. The algebraic
      difference (d) between i and s was assumed to represent detachment of the
      crossbridges. The time course of force development (f) by the reattached
      crossbridges could be estimated by subtracting an appropriately scaled d from i
      (or s). Ethylene glycol (20% in solvent) reduced the magnitude and the rate of
      rise of f, although it scarcely affected d, suggesting that ethylene glycol
      inhibited reattachment of the crossbridges but not their detachment. The presence
      of Ca2+ (50 microM) increased the magnitude of f, but did not affect its time
      course (130 microM ATP). Detachment, d, was not influenced by Ca2+ in terms of
      both extent and rate. The effect of Ca2+ in the presence of ethylene glycol was
      indistinguishable from that in its absence. Ethylene glycol did not seem to
      substantially affect the extent of Ca-regulation on the contractile activity.

PMID- 1401040
TI  - Inositol trisphosphate (InsP3) causes contraction in skeletal muscle only under
      artificial conditions: evidence that Ca2+ release can result from depolarization
      of T-tubules.
AB  - It has been proposed that in striated muscle inositol 1,4,5-trisphosphate (InsP3)
      may serve as a chemical transmitter linking membrane depolarization to Ca(2+)
      release from the sarcoplasmic reticulum. Key to that hypothesis of excitation
      concentration (EC) coupling was the observation that skinned muscle fibres
      contract on the application of InsP3. Yet skinned fibres do not always respond in
      this way, and in our hands intact fibres do not contract when InsP3 (1 microM-1
      mM) is microinjected into them. Glycerol-shocked fibres do contract, however, and
      so do intact fibres that have been depolarized to about -50 mV by increasing
      [K+]0. These observations and related pharmacological evidence support the
      hypothesis that InsP3 causes a low-level depolarizing current to cross the T
      tubular membrane. This current is sufficient to depolarize the T-tubules to the
      threshold for contraction only when the tubules are sealed over or when they are
      already close to the threshold. The InsP3-induced Ca2+ release sometimes observed
      in skinned muscle fibres and in vesicles derived from junctional sarcoplasmic
      reticulum probably often results from an action on sealed-over transverse
      tubules; in such situations it is an artifact of cell disruption. The fact that
      high concentrations of InsP3 do not cause contraction in normal muscle fibres is
      strong evidence against the hypothesis that InsP3 plays a central role in EC
      coupling in skeletal muscle.

PMID- 1401043
TI  - The annual meeting on Muscle Contraction and Cell Motility in Japan, January
      1992.

PMID- 1401044
TI  - Abstracts of the 1991 annual meeting on Muscle and Cell Motility Physiology.
      Tokyo, Japan, 29-30 November 1991.

PMID- 1401045
TI  - A survey of local health officials' views on current resources for public health
      services.

PMID- 1401046
TI  - Concepts of health promotion: dualities in public health theory.
AB  - The differing concepts of health promotion are reviewed in their historical
      context and development, and a unified concept is proposed which encompasses
      general as well as specific causative factors in the social environment. The
      implications for health promotion strategies are discussed.

PMID- 1401048
TI  - Abduction of children of political dissidents in Argentina and the role of human
      genetics in their restitution.
AB  - Between 1976 and 1983 a brutal military dictatorship governed Argentina. The most
      basic human rights were severely violated and the method of forced disappearances
      of approximately 30,000 political dissidents was instituted. In this process,
      about 300 babies and children of the disappeared victims were also abducted by
      the military and given to childless families linked to the security forces. Women
      whose children and grandchildren had disappeared organized themselves as
      Grandmothers of Plaza de Mayo to search for their missing loved ones. This search
      was aided by human geneticists from different parts of the world who provided the
      scientific basis to establish the genetic identification through "grandpaternity
      testing," and by mental health professionals who provided the psychological
      theory supporting restitution of appropriated children to their legitimate
      families. Thus far, close to 50 children have been located, identified and
      restituted.

PMID- 1401047
TI  - Trends in publicly financed prenatal and related services, 1975-1984.
AB  - We studied trends in Title V and health department financed prenatal and related
      services in U.S. countries from 1975-1984, years during which Medicaid and health
      insurance coverage for poor women were eroding. Information on prenatal services
      was obtained from background reports and telephone interviews with staff of State
      Maternal and Child Health programs. The number of counties providing prenatal
      care, particularly comprehensive care, rose considerably from 1975 to 1984; the
      largest rise occurred between 1982 and 1984. Federal initiatives accounted for
      about 25 percent of the increase in comprehensive care, while state-funded
      initiatives were responsible for the modest rise in counties offering routine
      care. The number of counties providing related components of care such as risk
      assessment and referral, obstetric or pediatric linkage with prenatal care, and
      outreach also rose markedly during the study years. Despite these secular trends,
      forty percent of U.S. counties did not offer prenatal care in health department
      operated or funded sites in 1984.

PMID- 1401049
TI  - Sales of alcohol to underage purchasers in three New York counties and
      Washington, D.C.
AB  - A study was conducted in which young males, under the legal alcohol purchase age
      of 21, attempted to purchase beer at grocery stores and other retail outlets.
      Underage purchases were attempted at a sample of stores in Washington, D.C.;
      Westchester County, New York: and Albany and Schenectady counties, New York. Beer
      was sold to the underage purchasers at 97 percent of the Washington, D.C. stores,
      80 percent of the Westchester County stores, and 44 percent of the Albany and
      Schenectady stores, despite the fact that such sales are illegal. Beer was more
      likely to be sold to the underage purchasers at smaller neighborhood stores in
      urban areas. Sales were least likely in Albany, which experienced recent police
      enforcement of the alcohol purchase age laws. Vigorous enforcement of the minimum
      purchase age laws is needed to reverse the current national trend toward more
      alcohol-related highway fatalities among youth.

PMID- 1401050
TI  - Policy alternatives for reducing tobacco sales to minors: results from a national
      survey of retail chain and franchise stores.
AB  - Minors' access to tobacco has become an important public health issue. Little is
      known, however, about the knowledge, attitudes, beliefs, and behavior toward
      access among executives from businesses that sell tobacco. This study examined
      access from the perspective of corporate and regional headquarters of retail
      chains and franchises that sell tobacco. A total of 148 U.S. companies with the
      largest overall retail sales volume that sold tobacco were asked to participate;
      91 agreed. The sample included grocery stores, convenience stores, gas station
      mini-marts, liquor stores, and drug stores. Data revealed at least moderate
      support for policies limiting youth tobacco access. Although most companies
      reported having in place policies to prevent minors from purchasing tobacco,
      these policies did not seem intensive. In addition, executives underestimated the
      extent of youth access. We conclude that the time is right for passage of bold
      policies to protect young people from tobacco.

PMID- 1401051
TI  - Disaster epidemiology: challenges for public health action.
AB  - Better epidemiologic knowledge of the causes of death and types of injuries and
      illnesses caused by disasters is clearly essential to determine appropriate
      relief supplies, equipment and personnel needed to respond effectively to such
      situations. The overall objective of disaster epidemiology is to scientifically
      measure and describe the health effects of disasters and contributing factors to
      these effects, with the goals of assessing the needs of disaster-affected
      populations, efficient matching of resources to needs, further prevention of
      adverse health effects, evaluation of program effectiveness, and contingency
      planning. In addition, the epidemiologist has an important role to play in
      providing informed advice about the probable health effects which may arise in
      the future, in establishing priorities for action and in emphasizing the need for
      accurate information as the basis for relief decisions. This presentation
      outlines a number of important areas where epidemiologists can contribute to
      making disaster management more effective.

PMID- 1401052
TI  - Long hours and fatigue: a survey of tractor-trailer drivers.
AB  - Fatigue and long driving hours have been implicated as risk factors in truck
      crashes. Under federal regulations, commercial drivers are permitted to drive no
      more than 10 hours before having an 8-hour break and cannot work more than 70
      hours over an 8-day period. Several studies have suggested that violations of
      these rules are common. A survey of long haul tractor-trailer drivers was
      conducted to estimate what proportion of drivers report that they regularly
      violate the hours-of-service rules and to identify the drivers most likely to
      commit hours-of-service violations. During December 1990 through April 1991, a
      total of 1,249 drivers were interviewed at truck safety inspection stations,
      truck stops, and agricultural inspection stations in Connecticut, Florida,
      Oklahoma, and Oregon. In each state, interviews were conducted during varying
      periods of the day over the course of seven days at inspection stations. Overall,
      89 percent of eligible drivers asked for interviews participated in the survey.
      According to self-reports, almost three-fourths of the respondents violate hours
      of-service rules. About two-thirds of the drivers reported that they routinely
      drive or work more than the weekly maximum. A primary impetus for violating rules
      appears to be economic factors, including tight delivery schedules and low
      payment rates. Many other driver, job, and vehicle characteristics were
      significantly associated with being an hours-of-service violator. The high
      prevalence of hours-of-service violations among tractor-trailer drivers is a
      problem in need of urgent attention. Potential measures to reduce the prevalence
      of rules violations include more enforcement directed toward carriers, wider use
      of electronic recorders, and increasing the number of rest areas.

PMID- 1401053
TI  - National drug policy in Nigeria. Interview by Daphne A. Fresle.

PMID- 1401054
TI  - Presidential address to the American Society for Clinical Investigation,
      Baltimore, Maryland, 2-6 May 1992.

PMID- 1401055
TI  - A unique recombination event resulting in a C4A*Q0,C4B*Q0 double null haplotype.
AB  - The fourth component of complement (C4) is encoded by two closely linked genes
      (C4A and C4B) within the MHC. Null alleles at either locus (C4AQ0 or C4BQ0) are
      relatively common, occurring at the C4A locus in approximately 10% of normal
      individuals and at the C4B locus in approximately 16% of normal individuals.
      However, the presence of the double null haplotype (C4A*Q0,B*Q0) on the same
      chromosome is extremely rare. We recently studied a 7-yr-old patient with
      recurrent sinopulmonary infections in whom we documented the mechanism by which
      the C4A*Q0,B*Q0 double null haplotype arose. Evaluation revealed significantly
      reduced levels of both C4 antigen and C4 hemolytic activity. Analysis of extended
      haplotypes in the family was performed using MHC typing and genomic DNA analysis.
      The patient was found to have a C4A*3,B*Q0 haplotype and a C4A*Q0,B*Q0 haplotype.
      The C4A*3,B*Q0 haplotype was contributed by the father. The mother possessed a
      C4A*Q0,B*1 haplotype and a C4A*3,B*1 haplotype. The first maternal haplotype was
      involved in a recombination event within the C4B locus on her other chromosome
      and resulted in a new C4B*Q0 null allele and the patient's C4A*Q0,B*Q0 haplotype.
      Segregation analysis mapped the recombination to a region 3' to the unique 6.4-kb
      TaqI restriction fragment of the maternal C4B locus. This is the first
      demonstration of a recombination event producing a C4 double null haplotype.

PMID- 1401056
TI  - Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and
      identification of a causal mutation in a French Canadian patient.
AB  - Type 1 hereditary tyrosinemia (HT1) is a metabolic disorder caused by a
      deficiency of fumarylacetoacetate hydrolase (FAH). Using a full-length FAH cDNA
      and specific antibodies, we investigated liver specimens from seven unrelated HT1
      patients (six of French Canadian and one of Scandinavian origin). The expression
      of FAH in livers of these individuals was analyzed at several molecular levels
      including mRNA, immunoreactive material (IRM), and enzymatic activity. Four
      phenotypic variants were differentiated by these assays: (i) presence of FAH mRNA
      without any IRM or enzymatic activity, (ii) decreased FAH mRNA, IRM, and
      enzymatic activity, (iii) moderately decreased FAH mRNA and IRM with severely
      reduced enzymatic activity, and (iv) undetectable FAH mRNA, IRM, and enzymatic
      activity. These various molecular phenotypes suggest that this disorder may be
      caused by a variety of FAH mutations. Interestingly, we found no apparent
      relationship between the clinical and the molecular phenotypes, except that
      patients with absent IRM and enzymatic activity tend to have higher levels of
      serum alpha-fetoprotein and an earlier clinical onset. To further analyze the
      molecular basis of HT1, the FAH cDNA of a patient designated as variant A was
      amplified and sequenced. An A-to-T transversion, which substitutes asparagine16
      with isoleucine (N16I), was identified. This patient was heterozygous as shown by
      direct sequencing of the amplified region and hybridization with allele-specific
      oligonucleotide probes. The N16I allele originates from the father and the second
      allele appears not to be expressed in the liver of the proband. CV-1 cells
      transfected with the mutant cDNA produced FAH mRNA, but no protein or hydrolytic
      activity, as predicted by the "A" phenotype of the patient. This is the first
      demonstration of heterogeneity in the expression of FAH at the levels of protein,
      mRNA, and enzymatic activity in the livers of HT1 patients and is the first
      identification of a causal mutationin this disease.

PMID- 1401057
TI  - Identification of a mutation in the coding sequence of the human thyroid
      peroxidase gene causing congenital goiter.
AB  - Thyroid peroxidase (TPO) is the key enzyme in the synthesis of thyroid hormones,
      and the TPO defects are believed to be the most prevalent causes of the inborn
      errors of thyroid metabolism. We investigated an adopted boy with iodide
      organification defect, who presented with florid hypothyroidism at the age of 4
      mo, poorly complied with thyroxine treatment, and developed a compressive goiter
      necessitating partial resection at the age of 12 yr. Biochemical studies revealed
      the absence of TPO activity in the resected tissue. Genomic DNA studies
      identified a 4 base-pair insertion in the eighth exon of the TPO gene, and showed
      that the patient was homozygous for this frameshift mutation. The direct genetic
      diagnosis of this mutation can be made by digestion of polymerase chain reaction
      products with NaeI restriction enzyme. This will help assessing its prevalence
      among the heterogenous genetic group of TPO defects.

PMID- 1401058
TI  - Mannose-induced dysmorphogenesis of metanephric kidney. Role of proteoglycans and
      adenosine triphosphate.
AB  - Because various fetal anomalies are seen in diabetic offspring, we examined the
      effects of sugars on proteoglycans (PGs): extracellular matrix (ECM)
      macromolecules modulating morphogenesis. 13-d-old mouse metanephric kidney
      explants were exposed to mannose for 7 d and labeled with [35S]sulfate, [35S]
      methionine, or [3H]thymidine. Mannose exposure caused reduction in kidney size
      and disorganization of ureteric bud branches with inhibition of glomerulogenesis.
      Tissue autoradiographic and immunofluorescence studies indicated decreased
      expression of sulfated PGs in ECMs. Helix pomatia lectin binding to D-GalNAc
      residues of glomerular epithelial cells was also reduced. Biochemical studies
      revealed decreased synthesis of sulfated PGs. PGs were of lower molecular weight
      with reduced charge density and increased chondroitin/heparan sulfate ratio.
      Immunoprecipitation of [35S]methionine-labeled proteins confirmed the reduction
      of PG core peptides. Intracellular ATP levels were reduced. The addition of 0.1
      mM ATP to culture media restored kidney size, the population of glomeruli, and
      the synthesis and characteristics of PGs to almost normal, with no detectable
      effect on the replication of cells as determined by [3H]thymidine incorporation.
      The effect of ATP could be partially blocked by the P2y-purinoreceptor, i.e.,
      reactive blue-2. Data suggest that mannose causes energy depletion by cellular
      ATP consumption and thus selectively alters the synthesis of heavily glycosylated
      proteins with rapid turnover, such as PGs, resulting in renal dysmorphogenesis.

PMID- 1401059
TI  - Combined enzyme defect of mitochondrial fatty acid oxidation.
AB  - A young girl presented with recurrent episodes of muscle weakness culminating in
      a severe attack of generalized muscle weakness. In the muscle mitochondria from
      the patient there was an abnormal pattern of intermediates of beta-oxidation with
      an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters, and 3
      oxoacylcarnitines. There was low activity of long-chain 3-hydroxyacyl-CoA
      dehydrogenase in mitochondria from all tissues. The activity of long-chain 2
      enoyl-CoA hydratase was low in muscle mitochondria and 3-oxoacyl-CoA thiolase
      activity measured with 3-oxohexadecanoyl-CoA as substrate was low in fibroblast,
      muscle, and cardiac mitochondria but only partial deficiency was present when the
      activity was measured with 3-oxooctanoyl-CoA. The activity of the long-chain 3
      hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase in
      fibroblasts from the patient's parents was intermediate between those of controls
      and the patient. The patient has a combined defect of the long-chain 3
      hydroxyacyl-CoA dehydrogenase, long-chain 3-oxoacyl-CoA thiolase, and long-chain
      2-enoyl-CoA hydratase which appears to be inherited in an autosomal recessive
      manner. This suggests there is a multifunctional enzyme catalyzing these
      activities in human mitochondria and that this enzyme is deficient in our
      patient.

PMID- 1401060
TI  - Augmented production of heparin-binding mitogenic proteins by preadipocytes from
      massively obese persons.
AB  - Basic fibroblast growth factor (bFGF) stimulates the replication of preadipocytes
      and inhibits their differentiation. In this study we explored whether the same or
      related polypeptides were produced locally and acted by paracrine/autocrine
      mechanisms in adipose tissue. Omental preadipocytes from 7 lean and 10 massively
      obese (> 170% reference) subjects were grown to confluence in subculture. Total
      RNA was hybridized with a synthetic deoxynucleotide for human bFGF. In the case
      of all cell strains, there was expression of two major bFGF transcripts, 7.0 and
      3.7 kb. Although there was considerable variation in the degree of expression,
      preadipocytes from massively obese subjects revealed much greater expression than
      did cells from the lean (P < 0.001). In studies of conditioned media prepared
      with preadipocytes, the presence of proteins belonging to the heparin-binding
      (fibroblast) growth factor family was indicated by Western blot analysis, for a
      66-kD protein with anti-(1-24)bFGF, and for a 32-kD protein with anti-(40-63)bFGF
      antibodies. The relative quantity of the 66-kD protein correlated with body mass
      index at r = 0.72. bFGF-related proteins probably function normally to maintain
      an appropriate complement of adipocyte precursors. The augmented expression of
      heparin-binding growth factors in preadipocytes from some massively obese people
      probably contributes to the excessive cellularity of their fat depots.

PMID- 1401061
TI  - Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3
      and soluble CD23.
AB  - Human epidermal keratinocytes (EK) secrete factors able to sustain the
      proliferation of early myeloid cells and, in particular, the generation of
      basophils. This activity was previously attributed to IL-3, although no
      definitive in situ demonstration of this cytokine was provided. In regard to the
      possible physiological relevance of these data, we investigated herein the nature
      of EK-derived factors responsible for basophil promotion. Our data show that EK
      derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both
      known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were
      also detected in EK. Blocking experiments using specific neutralizing monoclonal
      antibodies (mAb) further indicate that EK-derived basophil promoting activity is
      mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast
      to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL
      4, suggesting distinct regulatory mechanisms for their production.

PMID- 1401062
TI  - L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic
      humans.
AB  - Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even
      before the development of atherosclerosis. The purpose of this study was to
      determine whether infusion of L-arginine, the precursor of the endothelium
      derived relaxing factor, nitric oxide, improves endothelium-dependent
      vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in
      the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol =
      2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia
      (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative
      response to the endothelium-dependent vasodilator, methacholine chloride, was
      depressed in the hypercholesterolemic group, whereas endothelium-independent
      vasodilation, induced by nitroprusside, was similar in each group. Intravenous
      administration of L-arginine augmented the forearm blood flow response to
      methacholine in the hypercholesterolemic individuals, but not in the normal
      subjects. L-arginine did not alter the effect of nitroprusside in either group. D
      arginine had no effect on forearm vascular reactivity in either group. It is
      concluded that endothelium-dependent vasodilation is impaired in
      hypercholesterolemic humans. This abnormality can be improved acutely by
      administration of L-arginine, possibly by increasing the synthesis of endothelium
      derived relaxing factor.

PMID- 1401063
TI  - Prolonged exposure of human pancreatic islets to high glucose concentrations in
      vitro impairs the beta-cell function.
AB  - The aim of the present study was to clarify whether prolonged in vitro exposure
      of human pancreatic islets to high glucose concentrations impairs the function of
      these cells. For this purpose, islets isolated from adult cadaveric organ donors
      were cultured for seven days in RPMI 1640 medium supplemented with 10% fetal calf
      serum and containing either 5.6, 11, or 28 mM glucose. There was no glucose
      induced decrease in islet DNA content or signs of morphological damage. However,
      islets cultured at 11 or 28 mM glucose showed a 45 or 60% decrease in insulin
      content, as compared to islets cultured at 5.6 mM glucose. Moreover, when such
      islets were submitted to a 60-min stimulation with a low (1.7 mM) followed by a
      high (16.7 mM) concentration of glucose, the islets cultured at 5.6 mM glucose
      showed a higher insulin response to glucose than those of the two other groups.
      Islets cultured at the two higher glucose concentrations showed increased rates
      of insulin release in the presence of low glucose, and a failure to enhance
      further the release in response to an elevated glucose level. Islets cultured at
      28 mM glucose showed an absolute decrease in insulin release after stimulation
      with 16.7 mM glucose, as compared to islets cultured at 5.6 mM glucose. The rates
      of glucose oxidation, proinsulin biosynthesis, and total protein biosynthesis
      were similar in islets cultured at 5.6 or 11 mM glucose, but they were decreased
      in islets cultured at 28 mM glucose. These combined results suggest that lasting
      exposure to high glucose concentrations impairs the function of human pancreatic
      islets.

PMID- 1401064
TI  - Maturation of aldose reductase expression in the neonatal rat inner medulla.
AB  - Newborns are less able to concentrate urine than adults are. With development of
      the concentrating system and a hypertonic medullary interstitium, there is a need
      to generate intracellular osmolytes such as sorbitol, which is produced in a
      reaction catalyzed by the enzyme aldose reductase. We sought to discriminate
      between two possible mechanisms of aldose reductase induction during development:
      (a) a response to an osmotic stimulus generated by the concentrating mechanism;
      or (b) part of the genetic program for development of the kidney. We measured the
      change in aldose reductase mRNA and activity in terminal inner medullary
      collecting ducts (IMCDs) microdissected from Sprague-Dawley rats during the first
      month of life. Aldose reductase mRNA was assayed by Northern analysis of total
      RNA from inner medulla and by detection of the reverse transcription-polymerase
      chain reaction (RT-PCR) product obtained from single IMCDs using aldose reductase
      specific primers. Aldose reductase activity was measured in IMCDs taken from the
      same rats using a fluorescent microassay. Newborn rat IMCDs had minimal aldose
      reductase mRNA or activity, however mRNA was readily detected in IMCDs from rats
      older than 3 d of age, with peak expression occurring at 1-3 wk of age before
      decreasing to adult levels. In contrast, the mRNA level for a housekeeping
      metabolic enzyme, malate dehydrogenase, did not change during maturation. Aldose
      reductase enzyme activity was readily detectable by 6 d of age, peaked at 20 d,
      then decreased to adult levels. Urine osmolality remained < 600 mosmol/kg until
      16 d, then increased to > 1,100 mosmol/kg after 20 d. Thus, aldose reductase mRNA
      and activity increased before urinary osmolality reached 870 mosmol/kg. Because
      urine osmolality may not be indicative of inner medullary osmolality and because
      mother's milk may provide excessive free water to the pups under 3 wk of age,
      half of the animals in several litters were separated from their mothers for 1 d
      and inner medullary osmolality, in addition to urine osmolality, was measured by
      vapor pressure osmometry, while aldose reductase mRNA was assessed
      densitometrically in IMCDs after RT-PCR. Although fluid restriction resulted in a
      near doubling of urine osmolality and a tendency towards increased aldose
      reductase mRNA, there was no consistently significant increase in aldose
      reductase mRNA or inner medullary osmolality during the first 13 d of life
      compared to the suckling animals. On the other hand, 2-3-wk-old rats showed
      significant increases in aldose reductase mRNA, accompanied by increases in inner
      medullary osmolality, after fluid restriction. Thus, the dissociation between the
      increases in aldose reductase expression and inner medullary hyperosmolality
      indicates that the maturational induction of the aldose reductase gene is not a
      consequence of osmotic stimulation, but rather, part of the developmental program
      of the kidney.

PMID- 1401065
TI  - Human intrahepatic biliary epithelial cells proliferate in vitro in response to
      human hepatocyte growth factor.
AB  - In previous studies, intrahepatic human biliary epithelial cells (BEC) were
      isolated in high purity. However, these cells demonstrated only limited growth
      responses. Here we report that human BEC proliferate in response to human
      hepatocyte growth factor (hHGF), retain BEC-specific phenotype, and can be
      serially passaged. BEC showed dose-dependent growth in response to 0.01-100 ng/ml
      hHGF. The maximum S-phase labeling index reached 40% with half-maximal
      stimulation at 1 ng/ml. The response of cells from normal and primary biliary
      cirrhotic liver to hHGF was similar. Cultures were immunostained with specific
      antibodies and then processed for [3H]thymidine autoradiography. Proliferating
      cells expressed BEC-specific markers (HEA125 and CK-19), but were negative for
      desmin and factor VIII-related antigen. Occasional vimentin-positive cells were
      observed, but these were nonproliferative. In conclusion, cells responding to
      hHGF were clearly BEC in origin. The observation that HGF is mitogenic for BEC as
      well as hepatocytes has important implications. First, greater yields of
      intrahepatic BEC are available for subsequent studies of the pathogenesis and
      etiology of diseases of the biliary epithelium. Secondly, some means of
      regulating the cellular response to HGF in vivo must operate, in that HGF levels
      rise early after partial hepatectomy and yet BEC proliferate 24 h later than
      hepatocytes.

PMID- 1401066
TI  - Dietary cholesterol increases transcription of the human cholesteryl ester
      transfer protein gene in transgenic mice. Dependence on natural flanking
      sequences.
AB  - To investigate the regulation of expression of the human cholesteryl ester
      transfer protein (CETP) gene, transgenic mice were prepared using a CETP minigene
      linked to the natural flanking sequences of the human CETP gene. By using a
      transgene containing 3.2 kb of upstream and 2.0 kb of downstream flanking
      sequence, five different lines of transgenic mice were generated. The abundance
      of CETP mRNA in various tissues was determined on standard laboratory diet or
      high fat, high cholesterol diets. In three lines of transgenic mice the tissues
      expressing the human CETP mRNA were similar to those in humans (liver, spleen,
      small intestine, kidney, and adipose tissue); in two lines expression was more
      restricted. There was a marked (4-10-fold) induction of liver CETP mRNA in
      response to a high fat, high cholesterol diet. The increase in hepatic CETP mRNA
      was accompanied by a fivefold increase in transcription rate of the CETP
      transgene, and a 2.5-fold increase in plasma CETP mass and activity. In contrast,
      CETP transgenic mice, in which the CETP minigene was linked to a metallothionein
      promoter rather than to its own flanking sequences, showed no change in liver
      CETP mRNA in response to a high cholesterol diet. Thus (a) the CETP minigene or
      natural flanking sequences contain elements directing authentic tissue-specific
      expression; (b) a high cholesterol diet induces CETP transgene transcription,
      causing increased hepatic CETP mRNA and plasma CETP; (c) this cholesterol
      response requires DNA sequences contained in the natural flanking regions of the
      human CETP gene.

PMID- 1401067
TI  - Degradation of endogenous bacterial cell wall polymers by the muralytic enzyme
      mutanolysin prevents hepatobiliary injury in genetically susceptible rats with
      experimental intestinal bacterial overgrowth.
AB  - Jejunal self-filling blind loops with subsequent small bowel bacterial overgrowth
      (SBBO) induce hepatobiliary injury in genetically susceptible Lewis rats. Lesions
      consist of portal tract inflammation, bile duct proliferation, and destruction.
      To determine the pathogenesis of SBBO-induced hepatobiliary injury, we treated
      Lewis rats with SBBO by using several agents with different mechanisms of
      activity. Buffer treatment, ursodeoxycholic acid, prednisone, methotrexate, and
      cyclosporin A failed to prevent SBBO-induced injury as demonstrated by increased
      plasma aspartate aminotransferase (AST) and elevated histology scores. However,
      hepatic injury was prevented by mutanolysin, a muralytic enzyme whose only known
      activity is to split the beta 1-4 N-acetylmuramyl-N-acetylglucosamine linkage of
      peptidoglycan-polysaccharide (PG-PS), a bacterial cell wall polymer with potent
      inflammatory and immunoregulatory properties. Mutanolysin therapy started on the
      day blind loops were surgically created and continued for 8 wk significantly
      diminished AST (101 +/- 37 U/liter) and liver histology scores (2.2 +/- 2.7)
      compared to buffer-treated rats (228 +/- 146 U/liter, P < 0.05, 8.2 +/- 1.9, P <
      0.001 respectively). Mutanolysin treatment started during the early phase of
      hepatic injury, 16-21 d after surgery, decreased AST in 7 of 11 rats from 142 +/-
      80 to 103 +/- 24 U/liter contrasted to increased AST in 9 of 11 buffer-treated
      rats from 108 +/- 52 to 247 +/- 142 U/liter, P < 0.05. Mutanolysin did not change
      total bacterial numbers within the loop, eliminate Bacteroides sp., have in vitro
      antibiotic effects, or diminish mucosal PG-PS transport. However, mutanolysin
      treatment prevented elevation of plasma anti-PG antibodies and tumor necrosis
      factor-alpha (TNF alpha) levels which occurred in buffer treated rats with SBBO
      and decreased TNF alpha production in isolated Kupffer cells stimulated in vitro
      with PG-PS. Based on the preventive and therapeutic activity of this highly
      specific muralytic enzyme, we conclude that systemic uptake of PG-PS derived from
      endogenous enteric bacteria contributes to hepatobiliary injury induced by SBBO
      in susceptible rat strains.

PMID- 1401068
TI  - Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear
      magnetic resonance study.
AB  - To quantitate hepatic glycogenolysis, liver glycogen concentration was measured
      with 13C nuclear magnetic resonance spectroscopy in seven type II diabetic and
      five control subjects during 23 h of fasting. Net hepatic glycogenolysis was
      calculated by multiplying the rate of glycogen breakdown by the liver volume,
      determined from magnetic resonance images. Gluconeogenesis was calculated by
      subtracting the rate of hepatic glycogenolysis from the whole body glucose
      production rate, measured using [6-3H]glucose. Liver glycogen concentration 4 h
      after a meal was lower in the diabetics than in the controls; 131 +/- 20 versus
      282 +/- 60 mmol/liter liver (P < 0.05). Net hepatic glycogenolysis was decreased
      in the diabetics, 1.3 +/- 0.2 as compared to 2.8 +/- 0.7 mumol/(kg body wt x min)
      in the controls (P < 0.05). Whole body glucose production was increased in the
      diabetics as compared to the controls, 11.1 +/- 0.6 versus 8.9 +/- 0.5 mumol/(kg
      body wt x min) (P < 0.05). Gluconeogenesis was consequently increased in the
      diabetics, 9.8 +/- 0.7 as compared to 6.1 +/- 0.5 mumol/(kg body wt x min) in the
      controls (P < 0.01), and accounted for 88 +/- 2% of total glucose production as
      compared with 70 +/- 6% in the controls (P < 0.05). IN CONCLUSION: increased
      gluconeogenesis is responsible for the increased whole body glucose production in
      type II diabetes mellitus after an overnight fast.

PMID- 1401069
TI  - Major histocompatibility complex haplotypes and complement C4 alleles in systemic
      lupus erythematosus. Results of a multicenter study.
AB  - In a multicenter study more than 300 central European systemic lupus
      erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4
      phenotypes. For 174 SLE patients MHC haplotypes were determined by family
      segregation analysis, and for 155 patients C4 gene deletions were determined by
      TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQ0-C4B1-DR3
      and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings
      were confirmed by applying the haplotype frequency difference (HFD) method, which
      uses nontransmitted haplotypes from the family study as internal controls.
      Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in
      SLE patients independently of the two risk haplotypes. C4A gene deletions, but
      not silent C4AQ0 alleles, were increased in SLE patients and neither C4BQ0
      alleles nor C4B gene deletions were increased. The observed frequencies of
      homozygosity and heterozygosity for the two haplotypes and the frequencies of
      homozygotes for C4AQ0 and C4A deletions did not differ from the expected values,
      indicating that the risk for SLE is conveyed by single allele effects. In
      conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE
      patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against
      C4Q0 alleles being the decisive factors increasing susceptibility to SLE.

PMID- 1401070
TI  - Overexpression of the epidermal growth factor receptor in human pancreatic cancer
      is associated with concomitant increases in the levels of epidermal growth factor
      and transforming growth factor alpha.
AB  - The epidermal growth factor (EGF) receptor is activated by both EGF and
      transforming growth factor-alpha (TGF-alpha). Using immunohistochemical and
      immunoblotting techniques we now report that the EGF receptor, EGF, and TGF-alpha
      are found in both pancreatic acini and ducts in the normal human pancreas, and
      that all three proteins are expressed at higher levels in human pancreatic cancer
      tissues. Using in situ hybridization techniques, we also report that the mRNA
      encoding the EGF receptor, EGF, and TGF-alpha colocalize with their respective
      proteins. Northern blot analysis of total RNA indicates that, by comparison with
      the normal pancreas, the pancreatic tumors exhibit a 3-, 15-, and 10-fold
      increase in the mRNA levels encoding the EGF receptor, EGF, and TGF-alpha,
      respectively. Furthermore, by in situ hybridization, there is a marked increase
      in these mRNA moieties within the tumor mass. These findings suggest that EGF and
      TGF-alpha may participate in the regulation of normal pancreatic exocrine
      function, and that overexpression of the EGF receptor and its two principal
      ligands may contribute to the pathophysiological processes that occur in human
      pancreatic cancer.

PMID- 1401071
TI  - Influence of experimental hyperglycemia on microvascular blood perfusion of
      pancreatic islet isografts.
AB  - The influence of hyperglycemia on the microvascular blood perfusion of pancreatic
      islet isografts of Syrian golden hamsters was analyzed by direct visualization of
      the islet's microvasculature by means of in vivo fluorescence microscopy. The
      experiments were performed using the hamster dorsal skinfold preparation, which
      allows for quantitative analysis of the microcirculation of islets grafted on the
      striated skin muscle. Islets were isolated from inbred hamsters by collagenase
      digestion and subsequently transplanted in normoglycemic (controls; n = 8) and
      hyperglycemic (65 mg/kg streptozotocin intravenously; n = 10) recipients. In both
      groups, revascularization of the islet grafts was completed on day 10 after
      transplantation. Quantitative analysis of capillary blood perfusion on days 6,
      10, and 14 revealed no differences in functional capillary density and capillary
      red blood cell velocity of islets grafted into normoglycemic as compared to
      hyperglycemic animals. However, islet capillaries were significantly wider in
      hyperglycemic recipients (11.9 +/- 1.3 microns, P < 0.01) as compared to
      normoglycemic controls (8.9 +/- 0.4 microns). The increase of capillary diameters
      resulted in a significant rise (P < 0.01) of mean capillary blood perfusion from
      1.76 +/- 0.39 nl/min in controls to 2.88 +/- 0.63 nl/min in hyperglycemic
      recipients, indicating an increase in microvascular blood perfusion due to
      hyperglycemia. From these results it is concluded that hyperglycemia is
      associated with higher capillary blood perfusion in revascularized islet
      isografts, similarly as known for pancreatic islets in situ.

PMID- 1401072
TI  - Spontaneous production of transforming growth factor-beta 2 by primary cultures
      of bronchial epithelial cells. Effects on cell behavior in vitro.
AB  - The ability of airway epithelial cells to produce transforming growth factor-beta
      (TGF-beta) may be an important mechanism for the control of growth,
      differentiation, and repair of the airway epithelium. To determine whether airway
      epithelial cells are capable of producing TGF-beta, we examined primary cultures
      of bovine bronchial epithelial cells. Using a bioassay, TGF-beta activity was
      detected readily in media conditioned by bovine bronchial epithelial cells.
      Neutralizing antisera to TGF-beta 1 and TGF-beta 2 were used to demonstrate that
      the majority of the activity was of the TGF-beta 2 isoform. Interestingly, some
      of the TGF-beta activity was present in the conditioned media as "active" TGF
      beta, not requiring acid activation. The production of TGF-beta was variable,
      depending on cell density and the presence of retinoic acid. The presence of
      endogenously produced active TGF-beta in the culture media was shown to modulate
      the behavior of the cell cultures as evidenced by the effects of TGF-beta
      neutralizing antisera on cell size and fibronectin production. Our results
      suggest that active TGF-beta produced by airway epithelial cells may function in
      an autocrine or paracrine manner to modulate epithelial cell behavior.

PMID- 1401073
TI  - Glucose transport in human skeletal muscle cells in culture. Stimulation by
      insulin and metformin.
AB  - Primary human muscle cell cultures were established and the regulation of glucose
      transport was investigated. Primary cultures were allowed to proceed to the stage
      of myotubes through fusion of myoblasts or were used for clonal selection based
      on fusion potential. In clonally selected cultures, hexose (2-deoxy-glucose)
      uptake into myotubes was linear within the time of study and inhibitable by
      cytochalasin B (IC50 = 400 nM). Cytochalasin B photolabeled a protein(s) of
      45,000-50,000 D in a D-glucose-protectable manner, suggesting identity with the
      glucose transporters. In the myotube stage, the cells expressed both the GLUT1
      and GLUT4 glucose transporter protein isoforms at an average molar ratio of 7:1.
      Preincubation in media of increasing glucose concentrations (range 5-25 mM)
      progressively decreased the rate of 2-deoxyglucose uptake. Insulin elevated 2
      deoxyglucose uptake in a dose-dependent manner, with half maximal stimulation
      achieved at 3.5 nM. Insulin also stimulated the transport of the nonmetabolizable
      hexose 3-O-methylglucose, as well as the activity of glycogen synthase,
      responsible for nonoxidative glucose metabolism. The oral antihyperglycemic drug
      metformin stimulated the cytochalasin B-sensitive component of both 2
      deoxyglucose and 3-O-methylglucose uptake. Maximal stimulation was observed at 8
      h of exposure to 50 microM metformin, and this effect was not prevented by
      incubation with the protein-synthesis inhibitor cycloheximide. The relative
      effect of metformin was higher in cells incubated in 25 mM glucose than in 5 mM
      glucose, consistent with its selective action in hyperglycemic conditions in
      vivo. Metformin (50 microM for 24 h) was more effective than insulin (1 microM
      for 1 h) in stimulating hexose uptake and the hormone was effective on top of the
      stimulation caused by the biguanide, suggesting independent mechanisms of action.

PMID- 1401074
TI  - Evidence for defective transmembrane signaling in B cells from patients with
      Wiskott-Aldrich syndrome.
AB  - B lymphocytes from patients expressing the X chromosome-linked immune deficiency
      disorder, Wiskott-Aldrich syndrome (WAS), fail to produce antibodies in response
      to stimulation with polysaccharides and other type-2 T cell-independent antigens.
      To investigate whether this abnormality reflects a defect in the signal
      transduction cascade normally triggered by ligation of surface immunoglobulin
      (sIg) on B cells, we have examined early signaling events induced by anti-Ig
      antibody stimulation of EBV B lymphoblastoid cell lines from WAS patients and
      healthy controls. Despite the expression of comparable levels of sIg and sIgM on
      WAS and control EBV B cells, WAS cells failed to manifest the increased
      proliferation in response to anti-Ig treatment observed in the control cell
      lines. WAS and control EBV B cells also differed in the magnitude of the change
      in cytosolic free calcium ([Ca2+]i) induced by sIg ligation; WAS cells showed
      either markedly diminished or no changes in [Ca2+]i levels whereas control EBV B
      cells consistently showed increases in [Ca2+]i. Anti-Ig-induced changes in
      inositol phosphate release were also markedly reduced in WAS compared with
      control cells. As protein tyrosine phosphorylation is thought to represent a
      proximal event in the activation of B cells, inducing increases in [Ca2+]i by
      virtue of tyrosine phosphorylation of phospholipase C (PLC)-gamma, profiles of
      protein tyrosine phosphorylation and expression of tyrosine-phosphorylated PLC
      gamma 1 were compared between WAS and normal EBV B cells before and after sIg
      cross-linking. These studies revealed that in addition to defective mobilization
      of Ca2+, the WAS cells manifested little or no increase in tyrosine
      phosphorylation of PLC-gamma 1 or other intracellular proteins after sIg
      ligation. Together these results indicate the association of WAS with a defect in
      the coupling of sIg to signal transduction pathways considered prerequisite for B
      cell activation, likely at the level of tyrosine phosphorylation. The
      abnormalities observed in these early transmembrane signaling events in WAS EBV B
      cells may play a role not only in the nonresponsiveness of WAS patient B cells to
      certain T independent antigens, but also in the genesis of some of the other
      cellular deficits exhibited by these patients.

PMID- 1401075
TI  - Eosinophils express interleukin 5 and granulocyte macrophage-colony-stimulating
      factor mRNA at sites of allergic inflammation in asthmatics.
AB  - IL-5 and granulocyte macrophage-colony-stimulating factor (GM-CSF) are important
      regulators of eosinophil survival, proliferation, and effector function. To
      determine whether IL-5 and/or GM-CSF are generated by eosinophils at sites of
      allergic inflammation, we have used in situ hybridization with 35S-labeled RNA
      probes to study the expression of IL-5 and GM-CSF mRNA in bronchoalveolar lavage
      (BAL) eosinophils derived from asthmatics (n = 5) before and after endobronchial
      allergen challenge. Endobronchial allergen challenge induced a significant airway
      eosinophilia (pre-allergen challenge 0.6 +/- 0.5% eosinophilia vs post-allergen
      challenge 48.2 +/- 25.6% eosinophilia). Post-allergen challenge eosinophils
      expressed IL-5 and GM-CSF mRNA, but did not express IL-1 beta or IL-2 mRNA. To
      determine whether the IL-5 mRNA-positive cells coexpressed GM-CSF mRNA, double
      mRNA labeling experiments with a digoxigenin-11-UTP nonradioactive labeled IL-5
      RNA probe and a GM-CSF 35S-labeled RNA probe were performed. These studies
      demonstrated that individual eosinophils expressed one of four cytokine mRNA
      profiles (IL-5+, GM-CSF+, 34 +/- 13%; IL-5+, GM-CSF-, 34 +/- 5%; IL-5-, GM-CSF+,
      11 +/- 9%; IL-5-, GM-CSF-, 21 +/- 25%). The expression of IL-5 and GM-CSF by
      eosinophils at sites of allergic inflammation in asthmatics may provide an
      important autocrine pathway, maintaining the viability and effector function of
      the recruited eosinophils.

PMID- 1401076
TI  - Modulation of cisplatin sensitivity and growth rate of an ovarian carcinoma cell
      line by bombesin and tumor necrosis factor-alpha.
AB  - A twofold change in the cisplatin (DDP) sensitivity of 2008 human ovarian
      carcinoma cells is sufficient to reduce tumor response in vivo. The DDP
      sensitivity of these cells can be enhanced by activation of the epidermal growth
      factor and protein kinase C signal transduction pathways. We report here that two
      endogenous growth factors, bombesin and tumor necrosis factor alpha (TNF alpha),
      enhanced DDP sensitivity by factors of 1.7 +/- 0.1 (SD)-fold and 1.8 +/- 0.1 (SD)
      fold, respectively. Both agents also produced sensitization in an 11-fold DDP
      resistant 2008 subline. Neither bombesin nor TNF alpha changed the accumulation
      of DDP, glutathione content, or glutathione-S-transferase activity in 2008 cells.
      However, a 2-h exposure to both bombesin and TNF alpha was sufficient to increase
      2008 cloning efficiency by up to 2.6 +/- 0.1 (SD)-fold and 2.2 +/- 0.1 (SD)-fold,
      and it increased average colony size by 1.35 +/- 0.1 (SD)-fold and 1.55 +/- 0.1
      (SD)-fold, respectively. Bombesin increased intracellular free calcium, and this
      was blocked by the bombesin receptor-specific antagonist SC196, demonstrating
      that 2008 cells have functional bombesin receptors. These results indicate that
      bombesin and TNF alpha can enhance sensitivity to DDP in both DDP sensitive and
      resistant variants of a human ovarian carcinoma and that both agents serve as
      growth factors for this tumor.

PMID- 1401077
TI  - Chronic hyperkalemia impairs ammonium transport and accumulation in the inner
      medulla of the rat.
AB  - Previously we demonstrated in rats that chronic hyperkalemia had no effect on
      ammonium secretion by the proximal tubule in vivo but that high K+ concentrations
      inhibited ammonium absorption by the medullary thick ascending limb in vitro.
      These observations suggested that chronic hyperkalemia may reduce urinary
      ammonium excretion through effects on medullary transport events. To examine
      directly the effects of chronic hyperkalemia on medullary ammonium accumulation
      and collecting duct ammonium secretion, micropuncture experiments were performed
      in the inner medulla of Munich-Wistar rats pair fed a control or high-K+ diet for
      7-13 d. In situ pH and total ammonia concentrations were measured to calculate
      NH3 concentrations for base and tip collecting duct and vasa recta. Chronic K+
      loading was associated with significant systemic metabolic acidosis and a 40%
      decrease in urinary ammonium excretion. In control rats, 15% of excreted ammonium
      was secreted between base and tip collecting duct sites. In contrast, no net
      transport of ammonium was detected along the collecting duct in high-K+ rats. The
      decrease in collecting duct ammonium secretion in hyperkalemia was associated
      with a decrease in the NH3 concentration difference between vasa recta and
      collecting duct. The fall in the NH3 concentration difference across the
      collecting duct in high-K+ rats was due entirely to a decrease in [NH3] in the
      medullary interstitial fluid, with no change in [NH3] in the collecting duct.
      These results indicate that impaired accumulation of ammonium in the medullary
      interstitium, secondary to inhibition of ammonium absorption in the medullary
      thick ascending limb, may play an important role in reducing collecting duct
      ammonium secretion and urinary ammonium excretion during chronic hyperkalemia.

PMID- 1401078
TI  - Rabbit aortic smooth muscle cells express inducible macrophage scavenger receptor
      messenger RNA that is absent from endothelial cells.
AB  - Scavenger receptors mediate uptake of modified low density lipoproteins by
      macrophages. The accumulation of lipids via this process is thought to lead to
      foam cell formation in developing atherosclerotic plaques. Smooth muscle cells,
      which can also be converted to foam cells in vivo, have not been shown to express
      the same scavenger receptor previously cloned in macrophages. We report the
      cloning of two cDNAs that encode type I and type II scavenger receptors isolated
      from rabbit smooth muscle cells. The deduced protein sequences of these isolates
      are highly homologous to the scavenger receptors previously isolated from
      macrophages. Treatment of smooth muscle cells with phorbol esters induced a
      marked increase in scavenger receptor mRNA and a fivefold increase in receptor
      degradation activity. Rabbit venous endothelial cells in primary culture and a
      bovine aortic endothelial cell line had no detectable scavenger receptor mRNA,
      despite having scavenger receptor degradation activity. The latter finding
      suggests that endothelial cells may possess a scavenger receptor which is
      structurally distinct from that found in macrophages and smooth muscle cells. The
      isolation of cDNAs encoding the rabbit scavenger receptor should prove useful for
      in vitro and in vivo studies that employ the rabbit as a model of human
      atherosclerosis.

PMID- 1401080
TI  - Human fibroblasts synthesize elevated levels of extracellular matrix proteins in
      response to interleukin 4.
AB  - Interleukin 4 (also known as "B cell stimulatory factor-1"), a cytokine product
      of T lymphocytes and mast cells, stimulates synthesis of the extracellular matrix
      proteins, types I and III collagen and fibronectin, by human dermal fibroblasts
      in vitro. Stimulation of collagen by human recombinant (hr)IL-4 was also
      demonstrated in several fibroblastic synovial cell lines obtained from patients
      with rheumatoid arthritis and osteoarthritis. The stimulatory effect of hrIL-4 on
      fibroblast collagen synthesis was specifically neutralized by rabbit anti-hrIL-4
      Ig. IL-4 specifically increased the steady-state levels of types I and III
      procollagen and fibronectin mRNAs, with no effect on cytoplasmic beta-actin mRNA.
      Quantitative analysis of the levels of Pro alpha 1(I) collagen transcripts in IL
      4-treated fibroblast cultures was also corroborated by antisense RNA-mRNA
      hybridization and RNAse resistant hybrids which showed that IL-4-treated
      fibroblasts expressed higher levels of Pro alpha 1(I) collagen transcripts.
      Nuclear run-off transcription experiments indicated that IL-4 stimulated the
      rates of mRNA biogenesis. Based on these observations we conclude that IL-4
      exerts its effect on collagen and fibronectin synthesis at the pretranslational
      level, resulting in synthesis of these extracellular matrix proteins. These and
      other data suggest that IL-4 may be a "fibrogenic cytokine" that could be
      important in promoting biogenesis of extracellular matrix proteins in normal
      wound healing and in pathological fibrosis in which mast cells and T lymphocytes
      play a central role.

PMID- 1401079
TI  - Characterization of the cDNA of a broadly reactive neutralizing human anti-gp120
      monoclonal antibody.
AB  - The F105 mAb, identified in an HIV-1-infected individual, binds to a
      discontinuous epitope on the HIV-1 gp120 envelope glycoprotein, blocks the
      binding of gp120 to the CD4 viral receptor, and neutralizes a broad range of HIV
      1 isolates. This study reports the primary nucleotide and deduced amino acid
      sequences of the rearranged heavy and light chains of the mAb F105. This IgG1k
      mAb uses a VH gene member of the VH4 gene family (V71-4) and is productively
      rearranged with a D-D fusion product of the dlr4 and da4 germline DH genes and
      the JH5 gene. This rearranged heavy chain gene expresses the VH4-HV2a idiotope,
      which is seen in human monoclonal IgM cold agglutinins. The F105 Vk appears to be
      derived from the Humvk325 germline gene and is rearranged with a Jk2 gene. For
      both chains, the mutational pattern in the rearranged VH and VL genes is
      indicative of an antigen-driven process. These studies show that production of a
      broadly neutralizing anti-HIV-1 antibody that recognizes determinants within the
      CD4 recognition site of the envelope glycoprotein is achieved by rearrangement of
      the V71-4 and Humvk325 germline variable region genes along with selected
      individual point mutations in the rearranged genes.

PMID- 1401081
TI  - Activation of infectious virus from latent human immunodeficiency virus infection
      of monocytes in vivo.
AB  - Individuals infected with HIV may be asymptomatic for years before progressing to
      overt AIDS. Since HIV can latently infect monocytoid cell lines, we examined
      whether HIV latency occurs in monocytes in vivo. Freshly isolated monocytes from
      asymptomatic seropositive individuals examined before and after culture were
      positive for HIV DNA, but not RNA, as measured by polymerase chain reaction,
      showing that HIV latency occurs in monocytes in vivo. Coculture of these latently
      infected monocytes with Con A-activated T cells from HIV-negative normal donors
      stimulated 90% of the patients' samples and latently infected THP-1 to produce
      infectious virus. Neither Con A, resting T cells, nor T cell supernatants induced
      virus. Plasma membranes from activated T cells stimulated HIV production,
      suggesting cell contact induces factor(s) in monocytes to overcome latency. Thus,
      monocytes in AIDS patients harbor latent HIV inducible during an immune response,
      leading to T cell infection and viral-induced pathology.

PMID- 1401082
TI  - Cytokine regulation of human lung fibroblast hyaluronan (hyaluronic acid)
      production. Evidence for cytokine-regulated hyaluronan (hyaluronic acid)
      degradation and human lung fibroblast-derived hyaluronidase.
AB  - We characterized the mechanisms by which recombinant (r) tumor necrosis factor
      (TNF), IFN-gamma, and IL-1, alone and in combination, regulate human lung
      fibroblast hyaluronic acid (HA) production. Each cytokine stimulated fibroblast
      HA production. The combination of rTNF and rIFN-gamma resulted in a synergistic
      increase in the production of high molecular weight HA. This was due to a
      synergistic increase in hyaluronate synthetase activity and a simultaneous
      decrease in HA degradation. In contrast, when rTNF and rIL-1 were combined, an
      additive increase in low molecular weight HA was noted. This was due to a
      synergistic increase in hyaluronate synthetase activity and a simultaneous
      increase in HA degradation. Human lung fibroblasts contained a hyaluronidase
      that, at pH 3.7, depolymerized high molecular weight HA to 10-40 kD end products
      of digestion. However, hyaluronidase activity did not correlate with fibroblast
      HA degradation. Instead, HA degradation correlated with fibroblast-HA binding,
      which was increased by rIL-1 plus rTNF and decreased by rIFN-gamma plus rTNF.
      Recombinant IL-1 and rTNF weakly stimulated and rIL-1 and rTNF in combination
      further augmented the levels of CD44 mRNA in lung fibroblasts. In contrast, rIFN
      gamma did not significantly alter the levels of CD44 mRNA in unstimulated or rTNF
      stimulated cells. These studies demonstrate that rIL-1, rTNF, and rIFN-gamma have
      complex effects on biosynthesis and degradation which alter the quantity and
      molecular weight of the HA produced by lung fibroblasts. They also show that
      fibroblast HA degradation is mediated by a previously unrecognized lysosomal-type
      hyaluronidase whose function may be regulated by altering fibroblast-HA binding.
      Lastly, they suggest that the CD44 HA receptor may be involved in this process.

PMID- 1401083
TI  - Lipoprotein lipase-mediated uptake and degradation of low density lipoproteins by
      fibroblasts and macrophages.
AB  - Lipoprotein lipase (LPL), the rate limiting enzyme for hydrolysis of lipoprotein
      triglyceride, also mediates nonenzymatic interactions between lipoproteins and
      heparan sulfate proteoglycans. To determine whether cell surface LPL increases
      LDL binding to cells, bovine milk LPL was added to upregulated and nonupregulated
      human fibroblasts along with media containing LDL. LDL binding to cells was
      increased 2-10-fold, in a dose-dependent manner, by the addition of 0.5-10
      micrograms/ml of LPL. The amount of LDL bound to the cells in the presence of LPL
      far exceeded the capacity for LDL binding via the LDL receptor. Treatment of
      fibroblasts with heparinase and heparitinase resulted in a 64% decrease in LPL
      mediated LDL binding. Compared to studies performed without LPL, more LDL was
      internalized and degraded in the presence of LPL, but the time course was slower
      than that of classical lipoprotein receptor mediated pathways. In LDL receptor
      negative fibroblasts, LPL increased surface bound LDL > 140-fold, intracellular
      LDL > 40-fold, and LDL degradation > 6-fold. These effects were almost completely
      inhibited by heparin and anti-LPL monoclonal antibody. LPL also increased the
      binding and uptake by fibroblasts of apolipoprotein-free triglyceride emulsions;
      binding was increased > 8-fold and cellular uptake was increased > 40-fold with
      LPL. LPL increased LDL binding to THP-1 monocytes, and increased LDL uptake (4.5
      fold) and LDL degradation (2.5-fold) by THP-1 macrophages. In the absence of
      added LPL, heparin and anti-LPL monoclonal antibodies decreased LDL degradation
      by > 40%, and triglyceride emulsion uptake by > 50%, suggesting that endogenously
      produced LPL mediated lipid particle uptake and degradation. We conclude that LPL
      increases lipid and lipoprotein uptake by cells via a pathway not involving the
      LDL receptor. This pathway may be important for lipid accumulation in LPL
      synthesizing cells.

PMID- 1401084
TI  - Evidence for tissue-specific activation of renal angiotensinogen mRNA expression
      in chronic stable experimental heart failure.
AB  - The intrarenal renin-angiotensin system (RAS) may contribute to the
      pathophysiology of heart failure by the generation of angiotensin II at local
      sites within the kidneys. Angiotensin II may directly influence renal
      hemodynamics, glomerular contractility, and tubular sodium reabsorption, thereby
      promoting sodium and fluid retention in this syndrome. In the present study, we
      examined components of the circulating RAS as well as the intrarenal expressions
      of renin and angiotensinogen mRNA in rats with stable compensated heart failure
      (HF) 12 wk after experimental myocardial infarction. Renal angiotensinogen mRNA
      level in vehicle-treated HF rats increased 47%, as compared with sham control
      rats (P = 0.001). The increase in angiotensinogen mRNA levels was more pronounced
      in animals with medium (46%, P < 0.05) and large (66%, P < 0.05) infarcts than in
      those with small infarcts (31%, P = NS). There were no differences in liver
      angiotensinogen mRNA, circulating angiotensinogen, angiotensin II, plasma renin
      concentration (PRC), kidney renin content (KRC), and renal renin mRNA level
      between sham and HFv. In addition, in a separate group of rats with heart
      failure, we demonstrated that renal angiotensin II concentration increased
      twofold (P < 0.05) as compared with that of age-matched sham operated controls. A
      parallel group of heart failure rats (HFe, n = 11) was treated with enalapril (25
      mg/kg per d) in drinking water for 6 wk before these measurements. Blood pressure
      decreased significantly during treatment (91 vs. 103 mm Hg, P < 0.05). Enalapril
      treatment in HF rats increased renin mRNA level (2.5-fold, P < 0.005), KRC (5.6
      fold, P = 0.005), and PRC (15.5-fold, P < 0.005). The increase in renal
      angiotensinogen mRNA level observed in HFv rats was markedly attenuated in
      enalapril treated HF rats (P < 0.001), suggesting a positive feedback of
      angiotensin II on renal angiotensinogen synthesis. These findings demonstrate an
      activation of intrarenal RAS, but no changes in the circulating counterpart in
      this model of experimental heart failure, and they support the concept that the
      intrinsic renal RAS may contribute to the pathophysiology in this syndrome.

PMID- 1401085
TI  - On the interaction of IgG subclasses with the low affinity Fc gamma RIIa (CD32)
      on human monocytes, neutrophils, and platelets. Analysis of a functional
      polymorphism to human IgG2.
AB  - An allotypic form of the low affinity IgG Fc receptor Fc gamma RIIa (CD32),
      termed low responder (LR) because of its weak reactivity with mouse (m) IgG1,
      interacts efficiently with human (h) IgG2. Fc gamma RIIaLR is the first known
      human FcR that binds this IgG subclass. In this study, we analyzed the role of Fc
      gamma RIIa in binding of stable hIgG-subclass dimers, and in induction of T cell
      mitogenesis using chimeric anti-CD3 mAb. We demonstrate that the functional
      polymorphism to hIgG2 is expressed on the majority of Fc gamma R-bearing
      peripheral blood cells: monocytes, neutrophils, and platelets. We were able to
      assess Fc gamma RII-mediated IgG-binding without interference of other Fc gamma R
      classes, by blockade of Fc gamma RI on monocytes, and by using neutrophils of an
      individual deficient for the Fc gamma RIIIB gene. This study indicates as
      subclass specificity: hIgG3 >hIgG1,hIgG2 >> hIgG4 for Fc gamma RIIaLR and
      hIgG3,hIgG1 >> hIgG2 > hIgG4 for Fc gamma RIIaHR. Comparing the serum hIgG levels
      of individuals homozygous for the two fc gamma RIIa allotypic forms, we observed
      significantly lower hIgG2 serum levels in individuals expressing the hIgG2
      binding LR allotypic form. This observation may implicate that Fc gamma RIIa
      regulates hIgG subclass production or turnover in man.

PMID- 1401086
TI  - Insulin resistance in obese Zucker rat (fa/fa) skeletal muscle is associated with
      a failure of glucose transporter translocation.
AB  - The genetically obese Zucker rat (fa/fa) is characterized by a severe resistance
      to the action of insulin to stimulate skeletal muscle glucose transport. The goal
      of the present study was to identify whether the defect associated with this
      insulin resistance involves an alteration of transporter translocation and/or
      transporter activity. Various components of the muscle glucose transport system
      were investigated in plasma membranes isolated from basal or maximally insulin
      treated skeletal muscle of lean and obese Zucker rats. Measurements of D- and L
      glucose uptake by membrane vesicles under equilibrium exchange conditions
      indicated that insulin treatment resulted in a four-fold increase in the Vmax for
      carrier-mediated transport for lean animals [from 4.5 to 17.5 nmol/(mg.s)] but
      only a 2.5-fold increase for obese rats [from 3.6 to 9.1 nmol/(mg.s)]. In the
      lean animals, this increase in glucose transport function was associated with a
      1.8-fold increase in the transporter number as indicated by cytochalasin B
      binding, a 1.4-fold increase in plasma membrane GLUT4 protein, and a doubling of
      the average carrier turnover number (intrinsic activity). In the obese animals,
      there was no change in plasma membrane transporter number measured by
      cytochalasin B binding, or in GLUT4 or GLUT1 protein. However, there was an
      increase in carrier turnover number similar to that seen in the lean litter
      mates. Measurements of GLUT4 mRNA in red gastrocnemius muscle showed no
      difference between lean and obese rats. We conclude that the insulin resistance
      of the obese rats involves the failure of translocation of transporters, while
      the action of insulin to increase the average carrier turnover number is normal.

PMID- 1401089
TI  - The buccal fat pad in the closure of oro-antral communications: a study of 56
      cases.
AB  - This article describes the surgical technique, indications and possible
      complications of the use of the buccal fat pad in the closure of oro-antral
      communications (OAC), following tooth extraction, in 56 cases. The technique was
      successful in all patients and did not interfere with the buccal sulcus depth. It
      is concluded that it can be safely applied in the closure of OAC.

PMID- 1401088
TI  - Epiligrin, the major human keratinocyte integrin ligand, is a target in both an
      acquired autoimmune and an inherited subepidermal blistering skin disease.
AB  - Epiligrin, the major component of human keratinocyte extracellular matrix, serves
      as the preferred integrin ligand for alpha 3 beta 1 in plasma membranes and focal
      adhesions, and colocalizes with alpha 6 beta 4 in hemidesmosomes. In human skin,
      epiligrin is found in the lamina lucida subregion of epidermal basement membrane,
      where it is thought to be associated with anchoring filaments. We have identified
      three patients with an acquired mucosal predominant subepidermal blistering
      disease who have IgG anti-basement membrane autoantibodies that bind the lamina
      lucida/lamina densa interface of epidermal basement membrane, stain cultured
      human keratinocyte extracellular matrix, and immunoprecipitate disulfide linked
      polypeptides of 170, 145, 125, and 95 kD in human keratinocyte culture media in a
      pattern identical to that of P1E1, a murine monoclonal antiepiligrin antibody.
      Comparative immunoprecipitation studies of patient sera, P1E1, and GB3 monoclonal
      antibody show that epiligrin is identical to the antigen (i.e., BM600 or GB3
      antigen) previously reported to be absent from the skin of patients with lethal
      junctional epidermolysis bullosa, an inherited subepidermal blistering disease.
      Moreover, skin from a fetus with this disease shows no evidence of reactivity to
      patient antiepiligrin autoantibodies or P1E1. These studies show that
      antiepiligrin autoantibodies are a specific marker for a novel autoimmune
      blistering disease and that the epidermal basement membrane antigen absent in
      patients with lethal junctional epidermolysis bullosa is epiligrin.

PMID- 1401087
TI  - Differential expression of Op18 phosphoprotein during human thymocyte maturation.
AB  - Op18 (also termed prosolin/stathmin) is a highly conserved 18-kD cytosolic
      phosphoprotein expressed in low levels in mature resting G0 lymphocytes, but
      induced in late G1 and S phases after entry into the cell cycle. In addition to
      its induction in normal proliferating lymphocytes, Op18 has been found to occur
      at high levels in acute leukemias and in neuroendocrine tissue. The presence and
      rapid phosphorylation of Op18 after stimulation of proliferating cells correlates
      with subsequent functional responses of the cells, and, therefore, Op18 has been
      suggested to play a key role in signal transduction. The pattern of expression of
      Op18 during lymphoid development is of interest in view of its high levels of
      expression in acute leukemias, representing cells arrested at an immature stage,
      thus raising the possibility that Op18 may be regulated differently in mature and
      immature lymphoid cells. We report here that immature human thymocytes bearing
      the cortical double positive phenotype (CD4+CD8+) constitutively express high
      levels of Op18 protein. In contrast, in mature single positive thymocytes
      (CD3+CD4+ or CD3+CD8+), Op18 protein is expressed at a lower level, comparable to
      that seen in peripheral blood T cells. Cell cycle analysis demonstrated that most
      of the cells in the double positive thymocyte population expressing high levels
      of Op18 were noncycling and arrested in G0. Furthermore, there was no correlation
      between Op18 levels and the proportion of cycling cells in double positive
      thymocyte populations isolated from different thymuses. Interestingly, although
      Op18 protein levels did not increase any further after mitogenic stimulation of
      double positive thymocytes, an increase in Op18 phosphorylation was observed,
      thus coupling of Op18 phosphorylation to cell activation remained intact. Our
      results show that during lymphoid maturation Op18 expression is uncoupled from
      cell proliferation. These data also suggest that the ordered expression of
      proliferation-associated genes seen in mature T cells may be disrupted during T
      cell maturation.

PMID- 1401090
TI  - A revised method of conservative palatoplasty.
AB  - A revised method of conservative palatoplasty was performed on 21 patients with
      isolated cleft palate. The operation was principally based on von Langenbeck's
      method. The major modifications were that the mucosal layer was dissected instead
      of the mucoperiosteum and lateral mucosal deficits produced by medial
      displacement of the dissected mucosal flaps were covered with transpositioned
      buccal mucosal flaps. Postoperative early results were compared with those of the
      23 patients treated by Perko's mucosal flap operation. Our method was found to
      bring about a relatively long velum comparable to Perko's method and wound
      healing was more uneventful. Results at the age of 5 years were compared with
      those of the patients treated by Wardill's mucoperiosteal flap operation as well
      as with those treated by Perko's method. There were no statistically significant
      differences among the three groups in the maxillofacial development and speech
      results.

PMID- 1401091
TI  - Articulatory function in glossectomized patients with immediate reconstruction
      using a free jejunum flap.
AB  - Postoperative articulation in 18 glossectomized patients was investigated. The
      subjects were: 5 cases of tongue tumour, 7 cases of tumour of the anterior part
      of the floor of the mouth and 6 cases of tumour of the lateral part. A new
      modification of the Freiburger test for speech audiometry was used as test
      material. Then the articulatory function was assessed according to an overall
      score based on 180 monosyllables, the manner of production of 171 initial
      consonants and the place of production of 85 glossal sounds. The cases of tumour
      of the tongue and the lateral part of the floor of the mouth had excellent scores
      in all classes of sounds, which were compatible with the normative data. The
      subjects of tumour of the anterior part of the floor of the mouth had low overall
      scores, low scores for plosive and affricative sounds, and very low scores for
      sounds produced with the rear of the tongue. The relation between the site or
      amount of resection and subsequent articulation was significantly poor in all
      categories of sounds for the cases of anterior tumour, particularly in the
      movement of the posterior portion of the tongue even though it was not involved
      in the operation. In all groups there was a weak negative relation between the
      amount of resection and postoperative articulation. In reviewing the literature,
      reconstruction with a free jejunum flap was considered to lead to better
      articulation than reconstruction by other techniques. The need to assess
      postoperative function objectively was stressed, to compare the postoperative
      functions and to determine the indications for the reconstructive technique.

PMID- 1401092
TI  - The role of radiotherapy in the management of salivary gland carcinomas.
AB  - A retrospective study was performed on 44 patients with carcinoma originating in
      the major and minor salivary glands to examine the effects of postoperative
      radiotherapy on locoregional and distant control and survival. 22 patients were
      treated by surgery alone and the 22 other patients were treated by a combination
      of surgery and postoperative irradiation. In the surgery group, local recurrence
      developed in all 8 patients with evidence of residual disease at the surgical
      margins, whereas local control was achieved in 7 of 15 patients with positive
      surgical margins in the combination group and the control rate was related to the
      amount of residual disease. Neck metastasis, which developed in 13 patients
      (30%), was not affected by the status of surgical margins or by the treatment
      modality. On the other hand, the incidence of distant metastasis seen in 19
      patients (43%) was much higher in patients with positive surgical margins and the
      development of distant metastasis in these patients was not prevented by
      postoperative irradiation. The survival rates at 5, 10 and 15 years were 54, 48
      and 41%, respectively, for the irradiated patients, whereas the values for the
      patients treated by surgery alone were 75, 70 and 70%, respectively. The results
      indicate that postoperative irradiation is effective in controlling local
      recurrence but not neck and distant metastases. Wide excision with sufficient
      surgical margins followed by postoperative radiotherapy and systemic chemotherapy
      are essential to obtain a better prognosis.

PMID- 1401093
TI  - Cause of death in squamous cell carcinoma of the head and neck. An autopsy study
      on 31 patients.
AB  - A series of 31 autopsied patients, with a history of head and neck squamous cell
      carcinoma is reported, with the emphasis on the cause of death. There were 26
      males and 5 females; mean age being 64 years (range 44-88 years). Locoregional
      disease (LRD) was the cause of death in 19 patients (61%) and was present in 2
      patients dying of an unrelated cause. Distant metastasis (DM) was found in 8
      patients (26%) but had caused death in only 1 of them. A shorter survival time
      for patients with DM than for those without (8 months versus 13 months) indicates
      that DM is established early in the course of the disease. Therefore, a longer
      survival time will not result in an increase in DM and we infer that a better
      locoregional control will also not result in a real increase in DM but only in an
      apparent one, due to a shift of cause of death from LRD to DM in a group of
      patients that formerly would have died of LRD before the already present DM had
      become manifest.

PMID- 1401094
TI  - Foreign body in the sphenoid sinus.
AB  - Foreign bodies in the paranasal sinuses, especially in the sphenoid sinus are
      uncommon. We report a rare case of a foreign body in the sphenoid sinus after an
      occupational accident.

PMID- 1401095
TI  - Combined mandibular vertical ramus and body step osteotomies for correction of
      unusual skeletal and occlusal anomalies.
AB  - A technique is described involving the combined use of mandibular ramus
      osteotomies and body step osteotomies. The combined use of these osteotomies
      enables the surgeon to solve some of the most complicated skeletal and occlusal
      problems. The method has proved to be safe in that no complications have occurred
      in the 7 patients reported.

PMID- 1401096
TI  - Fractures of the maxillofacial region in children.
AB  - 83 children with maxillofacial fractures have been analyzed according to,
      aetiology, age, sex, type, and site of fractures. The results showed a high male
      to female ratio. Mandibular fractures were the commonest, in the condylar region
      in particular. The commonest causes in descending order were falls, bicycle
      accidents and at play.

PMID- 1401097
TI  - Disturbances of smell and taste after high central midface fractures.
AB  - Estimation of the senses of smell and taste in patients who had suffered a high
      central midface fracture between 1979 and 1989 was carried out. 180 of these
      patients were operated on for repositioning and fixation of their fractures. A
      written questionnaire was sent to 165 living patients, 109 individuals responded,
      a response rate of 66%. Of these patients, 38% claimed to suffer impaired ability
      to smell and 23% not to taste well. 64% mentioned unconsciousness after the
      trauma. With rising seriousness of the trauma, more disturbances of smell are
      found: from 25% of the nasal fractures, to 80% of the fronto-nasal-Le Fort
      fractures. In more than half of the cases of disturbance of smell, a simultaneous
      impairment of taste was reported. It can be concluded that disturbance of smell
      most often appears after fronto-maxillary and fronto-nasal fractures. However,
      the higher and more extensive the fracture is, the more frequently is
      unconsciousness reported. Consequently, impairment of smell can be attributed to
      the fracture itself, but also to a cerebral lesion located more proximally.

PMID- 1401098
TI  - Further development of titanium miniplate fixation for mandibular fractures.
      Experience gained and questions raised from a prospective clinical pilot study
      with 2.0 mm fixation plates.
AB  - Miniplate systems are often used instead of more rigid systems for the treatment
      of mandibular fractures. While the most stable fixation method for all mandibular
      fractures is the 2.7 mm plate, most fracture sites and types are eminently
      suitable for miniplate fixation via an intraoral approach. However, the
      relatively low stability of the miniplate systems compared with rigid plate
      systems limits the indications for their use in mandibular fracture treatment,
      especially when immediate postoperative function is desired. A more rigid
      miniplate which provides increased stability was studied. The results of a
      preliminary study and a clinical trial of a 2.0 mm titanium miniplate system are
      presented in this paper. The therapeutic consequences of the lesser stability
      afforded by small plate systems are discussed. Indications for miniplate fixation
      without additional immobilization are reviewed.

PMID- 1401099
TI  - Guided bone regeneration of cranial defects, using biodegradable barriers: an
      experimental pilot study in the rabbit.
AB  - The aim of this study was to test if a biodegradable barrier could be used to
      achieve proper bone healing of full-thickness trephine skull defects, applying
      the biological principle of guided tissue regeneration (GTR). Two New Zealand
      white rabbits were used. In each animal, 2 circular through-and-through bone
      defects with a diameter of 8 mm were created in the midline of the frontal and
      parietal bones of the calvarium. One defect was covered with the mucoperiosteal
      flaps without placement of an intervening membrane barrier (control). One test
      defect (test 1) was covered by a biodegradable, non-porous polylactic acid
      membrane on the outer (supra-calvarial) side of the defect, and 2 test defects
      (tests 2 and 3) were covered by similar membranes on both the outer and the inner
      aspects of the defects, prior to flap closure. 6 weeks postsurgically, the
      animals were sacrificed and the defect areas including surrounding tissues were
      harvested for histological preparation. The control defect was essentially
      occupied by supra-calvarial soft tissue, located in direct contact with the dural
      tissue. In the test cavities, there was a continuous bridge of regenerated bone
      extending from one edge of the defect to the other, although in test 1 not
      attaining the same thickness as the bone bordering the defect. In the 2 other
      test defects, the regenerated bone had reached a thickness almost corresponding
      to that of the surrounding bone. The bone regeneration was achieved without
      recourse to adjunctive bone graft materials.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401100
TI  - Intramuscular onchocercoma. Case report.
AB  - Onchocerciasis is characterized by the presence of numerous microfilariae in the
      skin, formation of subcutaneous nodules and eye lesions that can lead to
      blindness. We present a case, rather uncommon in our environment, in which an
      incomplete life cycle of the parasite, led to a single intramuscular nodule. The
      clinical symptoms and histological features are described, together with the
      treatment, using Ivermectin.

PMID- 1401101
TI  - Hibernoma: unusual location in the submental space.
AB  - A 40-year-old woman with a hibernoma, of unusual location in the submental space
      is described. The patient presented with a submental space mass, without other
      associated symptoms. There was no recurrence after a 4 year follow-up.

PMID- 1401102
TI  - Aneurysmal bone cyst of the maxilla--an association with tooth resorption.
AB  - The aneurysmal bone cyst is an uncommon lesion of the jaws. Cases involving the
      maxilla have been reported infrequently. Despite uncertainty as to the aetiology
      of the aneurysmal bone cyst, it is regarded as a benign lesion. Conservative
      surgical treatment with regular postoperative follow-up is recommended. The case
      described here presented with tooth mobility resulting from extensive root
      resorption. A review of the literature reveals that significant root resorption
      is not a commonly reported feature of aneurysmal bone cysts. For the present case
      we interpret the evidence as supporting a diagnosis of idiopathic root resorption
      complicated by the formation of a aneurysmal bone cyst.

PMID- 1401103
TI  - Epidermoid cyst in the temporomandibular joint after a dermal graft.
AB  - A very rare case of epidermoid cyst of the left temporomandibular join (TMJ)
      after a dermal graft inserted as the interposing material in the surgical
      correction of TMJ ankylosis is presented. Two years after the surgery, a cystic
      lesion the size of a walnut was observed in the TMJ region. The cyst contained an
      odorless, straw-coloured mucoid fluid and a wall lined by stratified squamous
      epithelium containing orthokeratin. It contained no hair follicles or sweat
      glands.

PMID- 1401104
TI  - Dermatography, a treatment for sequelae after head and neck surgery: a case
      report.
AB  - Two patients with discolouration fo skin grafts after head and neck surgery, were
      treated with dermatography, a refined method of tattooing, and with intra
      cicatricial keloidectomy, of which the results are described.

PMID- 1401105
TI  - The loadability of the 0.8-mm micro-system in thin midfacial regions--an animal
      experimental study.
AB  - The so-called 2-mm systems are well established in the osteosynthesis of the mid
      face. Due to the relatively thin soft tissue covering of most of the mid-face,
      however, the plates and screws of these systems often appear large, and disturb
      the patient because they are palpable and/or bulge through the skin. To avoid
      this disadvantage, more delicate systems have been designed. The question arises
      here, however, whether the more delicate systems could also be applied in thin
      mid-face regions that experience high functional loads. This study compares the
      functional loadability of 0.8-mm Luhr and 2.0-mm AO screws in an animal
      experimental model. Histological evaluation of the implant beds of the loaded
      screws showed significant differences in postoperative bone remodelling which
      could be correlated to the systems. Extrapolation of the results to the clinical
      situation suggests that care should be exercised when using Micro-Systems in
      highly loaded regions of the mid-face.

PMID- 1401106
TI  - Different patterns of mandibular fractures in children. An analysis of 220
      fractures in 157 patients.
AB  - 157 paediatric patients with a total of 220 mandibular fractures were evaluated
      retrospectively. All patients had been examined with the aid of
      orthopantomography. 72% of the children had fractures in the condylar region. The
      patients were divided into four age groups according to the development of the
      dentition (group A: 0-5 years, B: 6-9 years, C: 10-12 years, and D: 13-15 years).
      Bicycle accidents and falls were the two main causes of the fractures in all age
      groups. However, there were significant differences in the causes and location of
      the fractures between groups A+B and C+D. The proportion of condylar fractures
      decreased and the proportion of body and angle fractures increased with
      increasing age; fractures in the horizontal part of the mandible were mainly
      observed in groups C and D. Both aetiological factors and fracture patterns in
      the patients older than 10 years of age resembled those of adults. The
      differences observed should be taken into consideration in studies concerning
      mandibular fractures in paediatric patients. In this respect the age limit
      between the adult and child should probably be lowered significantly.

PMID- 1401107
TI  - Maxillofacial trauma: influence of HIV infection.
AB  - Between 1986 and 1990, 171 patients with mandibular and 129 with mid-face
      fractures were treated in our service. Both groups were separated into patients
      with HIV infection and patients without HIV infection. We carried out a
      retrospective review of these cases. The incidence of HIV+ve patients was higher
      in the mandibular fracture group (19.8%) than the group with mid-face fractures
      (7.75%). The most important aetiology of fractures was violence and the HIV
      infection was acquired through intravenous drug use (heroin). HIV infection was
      an independent associated factor where there was concomitant infection of
      mandibular fractures but not in mid-face fractures. In mandibular fractures,
      preoperative infections were significantly higher in HIV+ve patients (26.4%) than
      HIV-ve patients (6.5%) (p < 0.0001). Postoperative infections were higher in
      HIV+ve cases than HIV-ve cases, but this difference was not statistically
      significant (p > 0.05). Miniplates were a good osteosynthesis medium in HIV+ve
      patients and intermaxillary fixation seems to increase the infection rate in the
      HIV+ve group. The infections were treated with antibiotics with excellent results
      in preoperative infections and in the majority of postoperative cases, in both
      HIV+ve and HIV-ve patients.

PMID- 1401108
TI  - Extrusion of a microplate: an unusual complication of osteosynthesis.
AB  - A case is presented of an unusual complication of internal fixation of a
      midfacial fracture; the spontaneous extrusion of a microplate.

PMID- 1401109
TI  - Anatomical study of the valves of the superficial veins of the forearm.
AB  - The valves of the cephalic, basilic and median cubital veins were investigated in
      the superficial veins of the left forearm in 9 cadavers, aged 25-95. The radial
      forearm flaps involving these veins are of special clinicoanatomical importance.
      The following results were obtained: (1) Valves were most frequently evident at
      Site G of the cephalic vein. No valves were present in Section A-B, (2) type B
      valves were located at confluences, junctions and branches and were more frequent
      (54.7%) than Type A (45.3%) located in the straight trunks of superficial forearm
      veins, (3) Type 2 valves accounted for most (82.3%), and these were followed by
      Type 1 and Type 4b (5.9%), Type 4a (4.4%) and Type 3 (1.5%).

PMID- 1401111
TI  - Surgical treatment of exophthalmos and exorbitism: a modified technique.
AB  - A modified surgical technique for the treatment of exophthalmos caused by Graves'
      disease or meningioma is presented. It is based on the orbital expansion as
      presented by Tessier (1969). It consisted of a lateral marginotomy with extension
      to the superior and inferior orbital rim and removal of the great wing of the
      sphenoid bone. The osteotomised orbital rim segment was advanced and stabilised
      by interposition of a calvarial bone graft. Concomitant lipectomy was carried out
      when indicated. Seven patients were operated on. No major complications occurred.
      The advantages of the method are discussed.

PMID- 1401110
TI  - A new condylar positioning technique in orthognathic surgery. Technical note.
AB  - In two-jaw surgery, special importance must be attached to the maintenance of the
      condylar position, particularly in combination with rigid fixation, not only to
      enhance the stability of the post-operative result but also to avoid iatrogenic
      temporomandibular joint complications. The new positioning method reported herein
      is based on a mini fragmentation plate, which can be easily adapted to the bone
      surface. Reinforcement of the plate by autopolymerizing acrylate, injected into a
      silicone tube which is pushed over the plate, prevents any unnoticed deformation
      of the positioning device during surgery. In clinical use, this positioning
      method has proved to be more versatile and technically less difficult to perform
      than previous techniques, without any decrease in reliability.

PMID- 1401112
TI  - Reconstruction of full-thickness cheek defect affecting the oral commissure by
      galeal skin island flap: a case report.
AB  - This article describes the use of the galeal skin island flap in the
      reconstruction of a full-thickness cheek defect affecting the oral commissure,
      created after radical surgery in a 60-year-old patient suffering from carcinoma
      of the cheek. Advantages and drawbacks of the described technique are discussed.

PMID- 1401113
TI  - Doubling time of ameloblastoma metastasizing to the lung: report of two cases.
AB  - Two cases of malignant ameloblastoma with metastases to the lungs are reported.
      One originated in the mandible and the other in the maxilla. The doubling time of
      the metastatic lesions to the lungs were calculated according to Collins' method,
      and ranged from 129 to 201 days.

PMID- 1401114
TI  - Recurrent otitis media and parenting stress in mothers of two-year-old children.
AB  - This study examined the impact of recurrent otitis media on mothers' perceptions
      of themselves and of their 2-year-old children. Fifty-two mothers of children
      with and without histories of recurrent otitis media completed measures that
      rated the level of stress in the mother-child relationship at two points in time.
      The mothers of children who experienced six or more episodes of otitis media in
      the first 2 years of life rated their children as significantly more demanding at
      age two and at follow-up 6 months later than did the mothers of children who
      experienced no more than one episode of the illness. At the first point in time,
      these mothers also rated themselves as significantly more depressed and less
      competent than did control mothers, a pattern that was maintained at the follow
      up. Findings of the study suggest that recurrent otitis media early in life may
      contribute to adverse perceptions of child and self that may persist for some
      time after the child has been relatively disease free and further suggest that
      parental perceptions may mediate relationships between early recurrent otitis
      media and later developmental outcomes.

PMID- 1401115
TI  - Pattern of night waking and crying of Korean infants from 3 months to 2 years old
      and its relation with various factors.
AB  - Night waking and crying are very common in infancy and can cause problems for
      parents and families. This study surveyed 218 healthy Korean infants from 3
      months to 2 years old to determine their night waking and crying patterns. On
      average, 83% awoke and 28% cried more than once per night. Ninety-eight percent
      of the babies slept with a member of the family. Infants with transitional
      objects or nighttime habits (e.g., finger sucking, touching and/or playing with
      mother's or own hair, touching a part of mother's or own body) cried more
      frequently. In terms of the maternal response toward the crying babies, most of
      the mothers used traditional methods, such as patting/holding, feeding, changing
      diapers. Only one mother ignored the crying baby, and none used medication,
      delayed response, or white noise. Sixteen percent of the mothers indicated that
      their babies' crying constituted a problem for them.

PMID- 1401116
TI  - Cognitive patterns in school-age children with end-stage liver disease.
AB  - Although children with end-stage liver disease (ESLD) have been found to have
      cognitive delays, the relationship between patterns of cognitive function and
      diagnostic category, age of onset, duration and severity of disease has not been
      assessed before transplantation. Verbal and performance IQ (VIQ, PIQ) scores and
      scores on Bannatyne's cognitive factors for 43 children with ESLD were compared
      with those of 15 control children with cystic fibrosis (CF) and with existing
      normative data. Children with biliary atresia had deficits in PIQ, spatial and
      sequential scores. Children with alpha-1 antitrypsin deficiency did not differ
      significantly from CF controls but did show deficits compared with normative
      data. Children with onset of disease in the first year of life had deficits on
      all cognitive measures compared with both control groups. In contrast, children
      with later onset differed from the normative population only on VIQ and the
      acquired knowledge factor. In multiple regression analyses, duration of disease
      and indexes of liver dysfunction combine to predict cognitive scores. These
      preliminary findings suggest that children with early onset of liver disease are
      at high risk for cognitive impairment.

PMID- 1401117
TI  - Casualties from a junior-senior high school during the Persian Gulf War: toxic
      poisoning or mass hysteria?
AB  - Mass hysteria is a bizarre and uncommon epidemic phenomenon. The usual victims
      are adolescent females and school settings are frequent. The epidemics are
      characterized by the rapid onset of a constellation of symptoms and signs which
      resolve quickly in the absence of abnormal laboratory results and physical
      findings that confirm a specific organic cause. It is common, however, for
      unexpected laboratory results to cause confusion and promote controversy about
      suspected etiologies. These outbreaks are often noted to be associated with
      periods of uncertainty and social stress. We describe an epidemic involving the
      explosive onset and rapid resolution of a constellation of symptoms that sent 17
      seventh and eighth grade students and four teachers to the emergency department
      of a hospital after an apparent toxic gas exposure. Mildly elevated
      carboxyhemoglobin levels (for nonsmokers) in some patients raised concern that
      there had been exposure to excessive levels of carbon monoxide. Although no
      specific unusual stress could be identified at the school, the event took place 3
      1/2 weeks after the beginning of the Persian Gulf War.

PMID- 1401118
TI  - Psychosocial stressors and low birth weight: development of a questionnaire.
AB  - Low birth weight is a major public health problem because it is a major
      contributor to infant mortality as well as to various types of morbidity among
      young children. Of particular concern is that black women have an increased risk
      of low birth weight babies compared with white women. Many etiologic factors for
      low birth weight have been identified, but even within homogeneous strata of
      risk, black women have a greater risk of low birth weight babies than do white
      women. The reasons for this excess risk are not well understood. Available
      evidence suggests that exposure to psychosocial stressors is associated with
      adverse pregnancy outcomes. However, prior work in this area has been limited by
      the lack of a valid and reliable tool to assess exposure to stressors among
      pregnant women. We report on the development and testing of such a questionnaire,
      the Prenatal Social Environment Inventory. In this questionnaire, exposure to
      stressors is conceptualized and measured in the context of chronic stressful
      conditions. The questionnaire is self-administered and can be used in clinical
      settings with pregnant women. Findings of psychometric evaluations showed that
      the questionnaire has acceptable levels of 30-day temporal stability
      (reliability), internal consistency, and construct validity.

PMID- 1401119
TI  - Early onset intractable seizures: nonverbal communication after hemispherectomy.
AB  - The nonverbal communication skills of 10 children (mean age = 44.2 months) who
      underwent hemispherectomy for early onset intractable seizures were tested before
      and after surgery. A within-group analysis suggests that the 10 seizure-free
      children used more nonverbal communication after a mean follow-up period of 11.2
      months than before surgery. Young normal language age matches were available for
      the 4 older and higher functioning subjects in the sample. Before surgery, the
      surgical subjects used less requesting gestures than did the normal children.
      After surgery, these differences were no longer apparent. The patients also
      employed more gestures to focus an adult's attention on objects and events than
      language-age-matched normal children. The children who underwent left or right
      hemispherectomy used similar nonverbal communication behaviors. The study's
      findings suggest that children with early onset intractable seizures have
      impaired early social communication that improves to some extent after
      hemispherectomy.

PMID- 1401120
TI  - Can learning disabilities in children who were extremely low birth weight be
      identified at school entry?
AB  - This prospective study was designed to test the hypothesis that a significant
      proportion of extremely low birth weight (ELBW) children identified as "at risk"
      for school problems at age 5 years by the Florida Kindergarten Screening Battery
      (FKSB) will present with specific learning disability (LD) when retested at age 8
      years. A regional cohort of 81 of 84 ELBW survivors born between 1980 and 1982
      were reassessed at age 8 years by Wechsler Intelligence Scale for Children
      Revised (WISC-R), Wide Range Achievement Test-Revised (WRAT-R), and tests of
      motor function. The association of FKSB risk status and WRAT-R reading subtest
      for predicting general reading disability in the overall sample at age 8 years
      resulted in a sensitivity of 0.68, specificity of 0.48, and a likelihood ratio of
      1.3. Of the 43 "normal" children at age 5 years with no neurosensory impairments
      and IQ > or = 84 (McCarthy GCI), 49% were considered to be at "mild" to "high"
      risk for future LD. The prevalence of specific LD (reading disorder) at age 8
      years in children with normal IQ (WISC-R > or = 85) was 28%. The positive
      predictive value of the 5-year FKSB for identifying children with specific LD at
      age 8 years was 0.20 (sensitivity 0.33, specificity 0.48). We conclude the FKSB
      is not an efficient tool for predicting either general or specific LD in ELBW
      children.

PMID- 1401121
TI  - Diagnosing mental disorders in office-based pediatric practice.

PMID- 1401122
TI  - Think globally act locally: the WHO Healthy Cities Project.

PMID- 1401123
TI  - Temporomandibular disorders: past, present, and future.

PMID- 1401124
TI  - The role of the dental school in teaching TMD and orofacial pain.

PMID- 1401125
TI  - Predoctoral education for TMD and orofacial pain: a philosophical overview.

PMID- 1401126
TI  - Suggested curriculum guidelines for the development of predoctoral programs in
      TMD and orofacial pain.

PMID- 1401127
TI  - Curriculum outline for adjunctive predoctoral education in TMD and orofacial
      pain.

PMID- 1401128
TI  - Postdoctoral education for TMD and orofacial pain: a philosophical overview.

PMID- 1401129
TI  - Suggested curriculum guidelines for the development of postdoctoral programs in
      TMD and orofacial pain.

PMID- 1401130
TI  - Continuing education for TMD and orofacial pain: a philosophical overview.

PMID- 1401131
TI  - Suggested curriculum guidelines for the development of continuing education
      programs in TMD and orofacial pain.

PMID- 1401132
TI  - The prevalence of joint noises as related to age and gender.
AB  - The interdependence of joint noises on age and gender was studied mixed
      longitudinally in orthodontically treated subjects from 7 to 38 years of age. The
      prevalence of clicking signs and symptoms increased up to 25 years of age and
      leveled thereafter. Around age 19, a significant gender difference was present in
      clicking symptoms, with females reporting more clicks. The same pattern, although
      not significantly, was present for palpated clicks. Since male and female
      clicking prevalences are the same before and after adolescence, and since girls
      mature at an earlier age than boys, it is concluded that these noises reflect a
      maturity level rather than a multifactorial disorder. The prevalence of
      crepitation continued to increase slowly.

PMID- 1401133
TI  - Predicting response to treatment for temporomandibular disorders.
AB  - This study examined whether pretreatment psychological characteristics of
      temporomandibular disorder (TMD) patients were related to the response to
      treatment in a TMD and facial pain clinic. The care provided to patients was
      either an evaluation only or an evaluation followed by a course of physical
      medicine/dental procedures (occlusal appliances, physical therapy, anti
      inflammatory medications). Outcomes were assessed in terms of pain levels, jaw
      function difficulties, and satisfaction with care at 6 months posttreatment by
      phone and 16 months posttreatment by mail. There were no pretreatment differences
      between treated and evaluated patients except for higher pretreatment jaw
      function difficulty scores in the evaluated only patients. Factor analysis of
      pretreatment scores revealed distrust, pain, anxiety, and somatization.
      Somatization predicted follow-up pain levels at both follow-ups in the treated
      patients but only at the 16-month follow-up in the evaluated only patients.
      Pretreatment pain levels predicted posttreatment pain in both groups only at the
      6-month follow-up. Posttreatment jaw function difficulties were related
      inconsistently to the pretreatment dimensions, while satisfaction was not
      predicted by pretreatment scores except for a possible connection between this
      outcome and distrust. It is concluded that an overconcern about bodily
      functioning appears to decrease the likelihood that patients obtain pain relief
      from physical medicine care.

PMID- 1401134
TI  - Anatomical relationships and superior reinforcement of the TMJ mandibular fossa.
AB  - Only a few cases of condylar penetration into the middle cranial fossa have been
      documented in the literature. This study attempts to provide an anatomical
      explanation for this rare phenomenon. Mandibular (glenoid) fossa position in
      relation to important endocranial and exocranial structures located in close
      proximity to the TMJ, and relative condyle-fossa size, were evaluated on a dry
      skull sample. Additional osseous relationships were observed on cadaver material
      using dissection and x-ray. The anatomic relationships of the mandibular fossa
      and superior structures that appear to buttress it are described. It is concluded
      that the temporal squama that lies superior to the mandibular fossa provides a
      powerful buffer, which prevents condylar endocranial penetration in cases of an
      appropriate traumatologic mechanism.

PMID- 1401135
TI  - Changes in mandibular masticatory movements after insertion of nonworking-side
      interference.
AB  - To investigate the influence of nonworking-side interferences on mandibular
      masticatory movements and signs and symptoms of dysfunction of the masticatory
      system, an experimental balancing-side interference was introduced in 12 healthy
      subjects for 1 week. The individual response to the interference varied
      substantially. However, some of the movement variables were significantly changed
      immediately after insertion, but an adaptation of the neuromuscular system to the
      interference was evident at the end of the experimental period.

PMID- 1401136
TI  - Sleep movements in teethgrinders.
AB  - To investigate the nocturnal motor activity associated with teethgrinding, 12
      patients and 12 controls were recorded during sleep with the masseter muscle
      electromyogram (EMG) and the static charge-sensitive bed movement sensor. The
      frequency of body movements per hour was 21.4 in the teethgrinders and 14.0 (P
      less than .05) in the control group. The movement time was 87.4 seconds per hour
      in the teethgrinders and 55.2 seconds per hour (P less than .01) in the controls.
      The differences were most obvious in the body movements with temporal association
      to EMG elevation during the first stage of sleep. The number of isolated EMG
      elevations showed great interindividual variation and did not differ between
      groups. The teethgrinders complained more frequently of delayed sleep onset and
      daytime tiredness. The data suggest that the motor disturbance of teethgrinding
      is not limited to masticatory muscles but is manifested also as increased general
      body movement activity.

PMID- 1401137
TI  - The size and distribution of fiber types in jaw muscles: a review.
AB  - Histochemical enzyme reactions and physiological recordings of limb and jaw
      muscles have independently revealed three to five types of muscle fibers.
      Surprisingly, type II fibers are smaller than type I fibers in major human jaw
      muscles. This is the opposite of the situation in limb muscles. Human jaw muscles
      contain mixed fiber types. Type I fibers predominate in lateral pterygoid and
      type II fibers in digastric muscles. The masseters in carnivorans and rodents
      contain mainly type II fibers, whereas those of some herbivorans, including
      rabbits and bovids, contain mainly type I fibers. Attempts were made to describe
      the functional significance of some observations.

PMID- 1401138
TI  - Observer variation in functional examination of the temporomandibular joint.
AB  - Agreement between observers classifying TMJ sounds from data given in records of
      nonpatient adolescents was almost perfect in this interobserver study.
      Intraobserver and interobserver agreement in classifying all specific TMJ sounds
      at palpation and auscultation was acceptable to moderate (kappa value = 0.49 to
      0.74). The agreement was considerably more reliable when classifying only one
      specific TMJ sound. Measurements of linear jaw opening showed small interobserver
      differences (coefficient of variation = 2.4 to 3.8). The significant difference
      found in calculating the angular mandibular opening may be the result of
      difficulties in maintaining maximum passive opening.

PMID- 1401139
TI  - Acute closed lock in a patient with lupus erythematosus: case review.
AB  - Collagen failure has been shown to result in synovitis, joint adhesions, and
      internal joint derangement. This case report illustrates the similarities between
      patients with systemic lupus erythematosus and an internally deranged
      temporomandibular joint and patients with internal derangement with no lupus
      erythematosus. If abnormalities in intra-articular collagen tissue lead to
      adhesion formation and restrict normal mobility during translatory movements,
      joint mechanics would be compromised. Arthritic changes, vasculitis, and
      synovitis of systemic lupus erythematosus appear to be contributory factors in
      this pathophysiologic process. Diagnostic and therapeutic arthroscopic surgery
      was performed. Acute and chronic signs of synovitis were observed during surgery,
      and tissue samples were obtained for histologic interpretation.

PMID- 1401140
TI  - Symptom reporting in temporomandibular joint clicking: some theoretical
      considerations.
AB  - Analysis of research on psychological aspects of temporomandibular disorders
      suggests that self-reports of symptoms do not constitute reliable instruments for
      the measurement of physiological processes. In TMJ clicking, the actual
      physiological signal can be measured and compared with self-reports of the
      sounds. In this article a model is presented to describe perception,
      interpretation, and reporting of TMJ sounds. Three questionnaires are presented
      that measure aspects of these psychological processes. Recommendations are made
      for future research.

PMID- 1401141
TI  - Validation of PTSD measures for older combat veterans.
AB  - This study evaluated three nosologically similar older groups (Older PTSD, POW,
      and Older Psychiatric) and a group of Younger PTSD veterans from Vietnam. Group
      membership was derived from index admission diagnoses and clinical validation of
      status. Groups were compared on the MMPI, PTSD measures, background variables,
      health measures and an outcome measure. Results showed that the Older PTSD group
      is closer to the Younger PTSD group than to the other groups on the MMPI and PTSD
      measures and also that members of this group remain in the hospital longer than
      do members of the other older groups. Parameters of effective test classification
      showed the PTSD measures to be helpful in correct identification of this disorder
      for the older groups.

PMID- 1401142
TI  - Familiarity and anticipation of negative life events as moderator variables in
      predicting illness.
AB  - A 10-month longitudinal study with 79 university students examined the role of
      positive and negative life experiences on the subsequent development of health
      problems. The Life Experiences Survey (LES; Sarason, Johnson & Siegel, 1978) was
      modified to measure the potential role of five moderating variables on illness.
      Students gave monthly reports of life events experienced, as well as health
      status, on the Seriousness of Illness Rating Scale (Wyler, Masuda & Holmes,
      1968). Results indicated that both positive and negative life events were
      predictors of subsequent health problems. Negative life events that were familiar
      to the students and were unanticipated proved to be significant moderator
      variables; both factors were significant predictors of the number of health
      problems subsequently experienced.

PMID- 1401143
TI  - Psychological factors in the long-term prognosis of chronic low back pain
      patients.
AB  - This study appraised the significance of psychological factors in the long-term
      prognosis of patients with chronic low back pain (LBP). The MMPI ratings of 80
      long-term sick-listed LBP patients were set in relation to their disability
      pension status 6 to 12 years later. The number of elevated scales, in combination
      with the level of certain scales (HS and HY), proved to be a better predictor
      than profile patterns, advocated in some studies. Moreover, in a review of
      prognostic studies, the HS and HY scales appeared most frequently as significant
      predictors. That result also was confirmed in this study of long-term prediction
      of overall functional level. The results are discussed in relation to the
      concepts of pain-fear and sick role.

PMID- 1401145
TI  - The location of items of the Wiggins Content Scales on the MMPI-2.
AB  - The decision to exclude the Wiggins Content Scales from the MMPI-2 has hindered
      and, in many cases, may have prevented the ability to utilize the data collected
      over 25 years. There are questions with regard to the interpretation of some of
      the newer content scales of the MMPI-2, whereas most clinicians feel comfortably
      familiar, even if not entirely satisfied, with the Wiggins Content Scales of the
      MMPI. This report identifies the location and direction for scoring of items from
      the Wiggins Content Scales that appear on the MMPI-2. Preliminary data are
      presented and recommendations for utilizing these scales are offered.

PMID- 1401144
TI  - A construct validation study of the Haan defense scales.
AB  - This study tested the validity of the Haan (1965) psychological defense scales,
      which have shown promise for clinical and research assessment. Three subject
      samples participated: ex-inpatients (n = 80) from a longitudinal high-risk
      project, their spouses (n = 104), and private college students (n = 124). Valid
      defense scales were predicted to show a specific pattern of correlations with
      MMPI ego-strength and standard scales across all three cohorts, with measures of
      symptoms among the ex-inpatients, and with overall severity of pathology for all
      groups in a pattern consistent with Vaillant's defense model. The regression
      scale showed excellent validity, and projection received equivocal support, but
      the other scales were not validated. Denial appeared to reflect psychological
      health.

PMID- 1401146
TI  - Naivete and need for affection among pedophiles.
AB  - MMPI scores for items on the Harris and Lingoes (1955, 1968) subscales HY2 (need
      for affection) and PA2 (naivete) were compared among pedophiles (n = 50), non
      sexually deviant psychiatric patients (n = 25), and a general control group (n =
      50). Results indicated that pedophiles did not demonstrate a "naive need for
      affection," but, rather, a cynical need for affection. Scores on the Pedophelia
      (PE) Scale (Toobert, Bartelme, & Jones, 1959) also were compared, and no
      significant differences were found between the pedophiles and either control
      group, although a difference was found between the scores of the psychiatric
      control group and those of the general sample. Selected items from scale 4
      (Psychopathic Deviate) and scale 9 (Hypomania) also produced no significant
      differences among groups.

PMID- 1401147
TI  - Clinical construct validity of the Holden Psychological Screening Inventory
      (HPSI).
AB  - With a sample of 64 adult psychiatric patients, we examined the construct
      validity of the Holden Psychological Screening Inventory (HPSI) for a clinical
      population. Factor analysis supported the three-dimensional nature of the HPSI
      and the appropriateness of the instrument's scoring key. Reliability information
      confirmed the internal consistency of the inventory's scales. Clinical staff
      ratings were used as criteria, and analyses indicated that HPSI scales
      demonstrated convergent validity. Overall, findings extend previous nonclinical
      research on the HPSI and suggest that the instrument possesses construct validity
      for clinical applications.

PMID- 1401148
TI  - Age differences in self-reported symptoms of psychological distress.
AB  - Some investigators have found higher levels of distress in late adulthood, but
      others have reported no differences between younger and older adults or even
      lower levels of distress in their older samples. In the present investigation, a
      sample of adults who had attended the same university and ranged in age from 22
      to 86 were asked to complete the Brief Symptom Inventory. Subjects were divided
      into four age cohorts, and analyses were conducted to determine age-related
      differences in the reporting of symptomatology. Older adults were more likely
      than younger adults to report symptoms that reflected distress over physical
      ailments and memory problems, but young adults were more likely to report
      symptoms of a primarily psychological nature.

PMID- 1401149
TI  - The clinical application of the Psychopathy Checklist-Revised (PCL-R) in a prison
      population.
AB  - Psychopathy ratings that employed the PCL-R (Hare, 1985, 1991) were compared in
      one clinical and three research samples (total N = 285). Differences among the
      samples were not related to whether ratings were completed under the expressed
      promise of confidentiality of a research context vs. a pre-parole psychological
      assessment. The problem of decision errors in prediction is highlighted to
      address the difficulty in integrating the PCL-R into correctional policy. General
      issues related to the clinical application of the PCL-R also are discussed.

PMID- 1401150
TI  - Faking specific disorders: a study of the Structured Interview of Reported
      Symptoms (SIRS).
AB  - An untested assumption of malingering research is that persons who feign mental
      illness will not attempt to fake a particular disorder, but will be content to
      fabricate non-specific and possibly global psychiatric impairment. We tested the
      effectiveness of the Structured Interview of Reported Symptoms (SIRS) to detect
      feigning of three diagnostic groupings: schizophrenia, mood disorders, and PTSD
      on 45 psychologically knowledgeable correctional residents. We found that the
      SIRS maintained its powers of discrimination with respect to clinical samples.
      Similar research on faking specific disorders is needed on the MMPI-2 and other
      psychological measures.

PMID- 1401151
TI  - Styles of psychological adjustment in diabetes: a focus on key psychometric
      issues and the ATT39.
AB  - While knowledge of the biomedical factors in diabetes has grown in a steady and
      systematic fashion over the past 60 years, attempts to define, measure, and
      understand the relevant psychological constructs have only begun recently. In
      particular, there is need for psychometrically sound tests to tap these
      dimensions. This study examined the psychometric characteristics of the ATT39, a
      promising measure of psychological adjustment to diabetes. The results, based on
      three patient samples and using the FACTOREP factor-matching procedure, suggested
      that the ATT39 has a large single factor only. This new subscale appears
      clinically to measure the integration of diabetes and its treatment into the
      lifestyle and personality of a patient with diabetes.

PMID- 1401152
TI  - An evaluation of various WAIS-R factor structures in a psychiatric sample.
AB  - This report examines the factor structure of the Wechsler Adult Intelligence
      Scale-Revised (WAIS-R) in a sample of 229 psychiatric patients from two community
      mental health centers (ages 16 to 85). One-, two-, and three-factor solutions
      were evaluated. The robustness of an overall intelligence dimension was
      supported. The two-factor solution proved more informative and showed both that
      the Verbal and Performance domains are highly correlated and the presence of a
      second-order factor that may represent a kind of intellectual orientation or
      style. The three-factor solution provided the least compelling results and was
      not seen as a viable representation of the WAIS-R factor structure.

PMID- 1401153
TI  - Neuropsychological battery choice and theoretical orientation: a multivariate
      analysis.
AB  - In order to investigate the tests selected by neuropsychologists to make up
      clinical batteries, a large survey of neuropsychological test usage was cluster
      analyzed. This provided groupings of tests that are endorsed in common.
      Theoretical orientation within neuropsychology also was included in the analysis
      to determine which tests and clusters of tests are more and less associated with
      the reported orientation of the neuropsychologist. Fifteen clusters of tests were
      found. Strong and appropriate associations with the eclectic, hypothesis testing,
      process approach, Halstead-Reitan, Luria, and Benton orientations were seen.

PMID- 1401154
TI  - Correlates of medical compliance among hemophilic boys.
AB  - Twenty-nine males with hemophilia completed the Medical Compliance Incomplete
      Stories Test (M-CIST), and their scores were correlated with health care
      professionals' ratings of four aspects of medical compliance, along with measures
      of possible moderating variables. The results indicated that significant
      associations were found between most of the M-CIST category scores, particularly
      the Compliance/coping subscale, and the health care specialists' ratings of how
      well the children exhibited compliant responses to bleeding episodes, and inverse
      associations with the incidence of monthly bleeding episodes. The findings
      suggested that the M-CIST continues to demonstrate promise as an instrument to be
      used in studies of compliance among pediatric chronic illness patients.

PMID- 1401155
TI  - Efficacy of MMPI-2 validity scales and MCMI-II modifier scales for detecting
      spurious PTSD claims: F, F-K, Fake Bad Scale, ego strength, subtle-obvious
      subscales, DIS, and DEB.
AB  - This study compared 119 personal injury claimants' scores on MMPI-2 and MCMI-II
      malingering scales. Data from 55 pseudo-PTSD patients and 64 controls confirm the
      utility of the scales examined. The following cut-offs were most effective for
      identifying spurious PTSD: F greater than 62, F-K = greater than -4, Es = greater
      than 30, FBS = greater than 24 (men), FBS = greater than 26 (women), total
      obvious minus subtle = greater than 90, DIS = greater than 60, and DEB = greater
      than 60. Pseudo-PTSD patients were those who (1) claimed to be suffering a
      psychological injury (2) that was so severe that it was disabling (3) due to an
      experience that was entirely implausible as a candidate for PTSD criterion A in
      DSM-III-R and (4) scored T = 65 or higher on both PK and PS, the post-traumatic
      stress disorder subscales of the MMPI-2.

PMID- 1401156
TI  - Visual improvement after transethmoid-sphenoid decompression in optic nerve
      injuries.
AB  - Transethmoid-sphenoid decompression has been performed on 11 patients with
      indirect optic nerve injury. Visual improvement occurred in 8 patients, including
      4 patients with initial total blindness. Optic neuropathy improved even when
      there was a long interval, up to 92 days, between trauma and decompression. There
      is still controversy about the treatment of traumatic optic neuropathy. Our
      results suggest that surgery can be helpful in the management of this condition.
      Transethmoid-sphenoid optic nerve decompression is a minimally invasive procedure
      that gave, in this series, satisfactory results with low morbidity.

PMID- 1401157
TI  - Sixth nerve palsy as the initial presenting sign of metastatic prostate cancer. A
      case report and review of the literature.
AB  - Cranial nerve palsies secondary to metastatic prostate cancer are uncommon
      occurrences. Usually appearing late in the course of the disease, they are
      associated with a poor prognosis. We report a case of a 71-year-old man who
      initially complained of diplopia and was found to have a right sixth nerve palsy
      and hyperdeviation caused by a mass in the clivus. Biopsy of the mass and
      extensive systemic workup revealed metastatic adenocarcinoma of the prostate
      gland.

PMID- 1401158
TI  - Chronic idiopathic inflammation of the retropharyngeal space presenting with
      sequential abducens palsies.
AB  - We describe a patient who presented with sequential, bilateral abducens palsies
      associated with a mass of the nasopharynx. Biopsy of the mass showed chronic non
      specific inflammation and fibrosis. The diagnosis of idiopathic inflammatory
      pseudotumor was arrived at by exclusion of other known causes of inflammation of
      the retropharyngeal space. Magnetic resonance imaging suggested that injury to
      the sixth cranial nerves probably occurred as they traversed the dura and
      subarachnoid space overlying the clivus.

PMID- 1401159
TI  - Papilledema and intraspinal lumbar paraganglioma.
AB  - Optic nervehead swelling is most frequently caused by ocular or intracranial
      lesions. The case presented here demonstrates that the spinal subarachnoid space
      must also be considered as a potential site for a lesion causing optic nervehead
      swelling. A 56-year-old man is presented with an intraspinal lumbar paraganglioma
      associated with increased cerebrospinal fluid protein, papilledema, transient
      obscurations of vision, and back pain. This may be the first reported case of a
      paraganglioma associated with optic nervehead swelling. Magnetic resonance
      imaging of the lumbosacral region revealed the lesion noninvasively. The
      papilledema, transient obscurations of vision, and back pain resolved after
      resection of the tumor. The mechanisms are not defined for optic nervehead
      swelling in association with spinal tumors in general and paraganglioma in
      particular. The measured abnormal elevation of cerebrospinal fluid protein may
      have resulted in increased intracranial pressure and papilledema.

PMID- 1401160
TI  - High myopia causing bilateral abduction deficiency.
AB  - We present two cases of degenerative myopia with abduction deficiency. Three
      mechanisms can explain the defect in the abduction: (a) the size of the long
      globe filling the space of the orbits, (b) the tightness of the medial recti due
      to long axis of the globe, and (c) longstanding esotropia becoming decompensated
      later in life. We believe that high myopia is not a well-known cause of abduction
      deficiency, and it should be considered in the differential diagnosis.

PMID- 1401162
TI  - Neuroretinitis due to seronegative syphilis associated with human
      immunodeficiency virus.
AB  - Syphilis serologic testing is felt to be extremely reliable. A case of syphilitic
      neuroretinitis is reported where serologic testing was negative due to human
      immunodeficiency virus infection. A prompt response to high-dose intravenous
      penicillin was achieved.

PMID- 1401161
TI  - Interstitial keratitis and iridoschisis in congenital syphilis.
AB  - Bilateral interstitial keratitis and iridoschisis are reported in four cases with
      extraocular stigmata of congenital syphilis and positive syphilis serology. The
      iridoschisis was extensive in two cases giving the iris an unusual ragged
      appearance, while it was slight in one case. Iridoschisis may suggest the
      diagnosis of congenital syphilis, especially when interstitial keratitis is mild.
      Chronic open-angle glaucoma should be excluded in all patients with interstitial
      keratitis and iridoschisis.

PMID- 1401163
TI  - Prolonged course of bilateral acute idiopathic blind spot enlargement.
AB  - We report a patient with bilateral "acute idiopathic blind spot enlargement"
      (AIBSE) in whom visual symptoms and enlarged blind spots persisted for over 6
      years and preceded the development of peripapillary hyperfluorescence on
      fluorescein angiography. These findings confirm the prolonged course that AIBSE
      can sometimes take and the suggestion that this rare disorder is due to
      peripapillary retinal dysfunction.

PMID- 1401164
TI  - Aneurysmal oculomotor nerve palsy in an 11-year-old boy.
AB  - Cerebral aneurysms are rare in children. When they occur, they usually present
      with a history of subarachnoid hemorrhage. Gabianelli et al. (1) recently
      reported a 14-year-old girl with an isolated oculomotor nerve palsy due to
      aneurysm. In their discussion, they state that arteriography is, "Unnecessary in
      patients under 10 (years of age) if the symptoms and signs of subarachnoid
      hemorrhage are absent or high resolution computerized tomography scan or adequate
      magnetic resonance imaging scan is normal." To date, their patient is the
      youngest reported in the literature with an isolated oculomotor nerve palsy
      proved to be caused by cerebral aneurysm. We report herein an 11-year-old boy who
      presented with an oculomotor nerve palsy due to aneurysm with minimal preceding
      symptoms and no other signs of intracranial disease.

PMID- 1401165
TI  - Absence of the relative afferent pupillary defect with monocular temporal visual
      field loss.
AB  - We report five patients with monocular temporal visual field abnormalities who
      did not have clinically detectable relative afferent pupillary defects. The
      causes for the field defects were posterior ischemic optic neuropathy,
      craniopharyngioma, pituitary adenoma, pseudotumor cerebri, and traumatic optic
      neuropathy. We discuss the possible explanations for our observations,
      considering the known anatomy of the pregeniculate visual pathways and the
      afferent pupillary pathways.

PMID- 1401166
TI  - Suprasellar tumors of maldevelopmental origin in Klinefelter's syndrome. A report
      of two cases.
AB  - Patients with Klinefelter's syndrome may have a predisposition for the
      development of neoplasia, particularly extragonadal germ-cell tumors, but a
      suprasellar location is rarely reported. The clinical and neuroradiologic
      features in two patients with Klinefelter's syndrome and dysmorphic suprasellar
      masses of maldevelopmental origin (presumably lipomas or lipodermoids) are
      described. One patient had bilateral optic atrophy and decreased vision. To our
      knowledge, only one similar case (a suprasellar hamartoma) has been previously
      reported in association with Klinefelter's syndrome.

PMID- 1401167
TI  - Permanent homonymous hemianopias following migraine.
AB  - Two patients with migraine and repetitive visual field defects of homonymous
      hemianopic type are reported. The visual field defects were confirmed by Goldmann
      perimetry and automated static perimetry. Neither computed tomography nor
      magnetic resonance imaging showed abnormal findings. Decreased cerebral blood
      flow at the left basal ganglion area was the only abnormal finding detected in
      one patient by 123I-IMP (iodoamphetamine)-SPECT (single photon emission computed
      tomography), which is applicable to right homonymous hemianopia. A visual field
      test that includes the current automated static perimetry is important to the
      diagnosis and the subsequent treatment of patients with migraine, particularly
      those who have experienced visual negative phenomena.

PMID- 1401168
TI  - Transient oculomotor nerve synkinesis in non-Hodgkin's lymphoma.
AB  - A patient with large cell malignant lymphoma presented with transient left
      oculomotor nerve synkinesis, left trigeminal and abducens nerve palsies. Magnetic
      resonance imaging showed thickening of the oculomotor and trigeminal nerves
      characteristic of central nervous system lymphoma. To our knowledge, this is the
      first reported case of transient oculomoter nerve synkinesis in non-Hodgkin's
      lymphoma. The rapid onset and quick recovery of the synkinesis following 2 weeks
      of chemotherapy support the ephatic transmission theory.

PMID- 1401169
TI  - Myxoma mix-up. A case report.
AB  - We present a 63-year-old lady who had atrial myxoma. The diagnostic difficulties
      distinguishing this from giant cell arteritis are highlighted. In particular,
      both conditions caused choroidal and retinal infarcts, anterior ischaemic optic
      neuropathy, with raised acute phase reactants. The authors stress the importance
      of continued ophthalmoscopy as the fundal changes become more apparent.

PMID- 1401170
TI  - Myasthenia gravis-like syndrome induced by topical ophthalmic preparations. A
      case report.
AB  - This case study reports on a 64-year-old female who presented for cataract
      surgery. She relayed a history of allergic responses to local anesthetics such as
      xylocaine, but was otherwise in good health. Upon instilling ophthalmic
      preparations into her eyes during routine ocular examination, she developed
      general muscular weakness but not other allergic-like symptoms. Further
      investigation established her myasthenic-like syndrome to be precipitated by an
      ophthalmic mydriatic preparation. She was able to undergo uneventful cataract
      surgery and enjoy 20/20 vision postoperatively, with proper management.

PMID- 1401171
TI  - A pragmatist's approach to pathology costing: the Welsh Datatree project.
AB  - The Datatree costing project in Wales has provided the Welsh pathology
      laboratories with a standard costing package that allows pathologists to
      understand how their own laboratory's test costs are compiled. The software
      provides answers to the question "what if? ..." and shows instantly the effect of
      salary or consumable cost alterations. Resource management at a laboratory level
      is enhanced by a greater knowledge of costs, particularly in relation to volumes
      of work. Perhaps this is one of the stepping-stones across the river to the "open
      market." In the United Kingdom NHS any information of this kind must be regarded
      as invaluable.

PMID- 1401172
TI  - Bodies recovered from water: a personal approach and consideration of
      difficulties.

PMID- 1401173
TI  - Expression of Ki-67 nuclear antigen in B and T cell lymphoproliferative
      disorders.
AB  - AIMS: To determine whether the proliferation rates of tumour cells may relate to
      prognosis and reflect disease activity. METHODS: Blood mononuclear cells from 155
      patients with B cell (n = 120) or T cell (n = 35) chronic lymphoproliferative
      disorders were tested with the monoclonal antibody Ki-67 by indirect
      immunoperoxidase or immunoalkaline phosphatase techniques. B cell diseases
      included chronic lymphocytic leukaemia (CLL), CLL in prolymphocytic
      transformation (CLL/PL), prolymphocytic leukaemia (B-PLL) and non-Hodgkin's
      lymphoma (B-NHL) in leukaemic phase. The T cell diseases comprised large granular
      lymphocyte (LGL) leukaemia, T-PLL, and T-NHL. RESULTS: These showed significantly
      higher proportions of Ki-67 positive cells in T cell (11.2%) than in B cell
      (2.9%) disorders (p < 0.001). The highest values were found in NHL of both B and
      T cell types, particularly when low grade disease transformed to high grade. The
      lowest percentages of Ki-67 positive cells were found in CLL (1.4%) and LGL
      leukaemia (1.7%); intermediate values were seen in B PLL (3.3%) and T PLL (5.8%).
      CONCLUSIONS: There is a positive correlation between prognosis and proliferation
      rates in chronic B and T cell lymphoproliferative disorders. Estimation of Ki-67
      in circulating leukaemic cells could be used to determine prognosis in low grade
      malignancies.

PMID- 1401174
TI  - Human tonsil intraepithelial B cells: a marginal zone-related subpopulation.
AB  - AIMS: To determine if intraepithelial B cells in reactive human palatine tonsils
      were similar to the marginal zone cells of the spleen and Peyer's patches.
      METHODS: Reactive human palatine tonsils were studied using conventional methods
      of light microscopy, electron microscopy, and a panel of monoclonal antibodies
      for leucocyte common antigens. RESULTS: Clinically important numbers of marginal
      zone-related B cells around the mantle zone were absent in lymphoid follicles,
      but in the cryptal epithelium there were abundant lymphoid cells with centrocyte
      like nuclei and clear cytoplasm, intermingled with macrophages and plasma cells.
      The immunophenotype of these intraepithelial B cells was distinctive and similar
      to that found in the splenic marginal zone cells (IgM+, IgD-, CD23-, CD10-,
      CD35+, CD21+, bc12+, KB61+). CONCLUSIONS: Intraepithelial B cells in human tonsil
      could represent the counterpart of the marginal zone described in Peyer's
      patches. Their presence within the epithelium could reflect the destination for
      the malignant B cells in the lymphoepithelial lesion of mucosa associated
      lymphoid tissue (MALT) lymphomas. Human palatine tonsil lymphoid tissue has
      morphological, immunophenotypic, and pathological features similar to those of
      MALT.

PMID- 1401175
TI  - Non-isotopic in situ hybridisation and immunophenotyping of infected cells in the
      investigation of human fetal parvovirus infection.
AB  - AIMS: To compare the use of biotinylated and digoxigenin labelled probes for
      diagnosis of human fetal parvovirus B19 infection in formalin fixed, paraffin wax
      embedded tissues; and to assess the cellular distribution of the virus in
      positive cases. METHODS: Sections of lung tissue from 23 cases of anatomically
      normal non-immune fetal hydrops presenting between 1984 and 1989, and from 13
      control cases of hydrops due to chromosomal abnormality were probed for B19 DNA
      by in situ hybridisation using both biotinylated and digoxigenin labelled probes.
      The distribution of the virus was then investigated in all cases of fetal B19
      infection confirmed in this laboratory to date (n = 11) by combining in situ
      hybridisation for viral DNA (using the digoxigenin system) with
      immunohistological labelling for a range of cellular antigens. RESULTS: Five
      unequivocal cases of B19 infection were identified among the 23 fetuses with
      unexplained hydrops using both probe labels. When combined with data from
      previous studies of the period 1974-1983, the results indicate that B19 infection
      was responsible for 27% of cases of anatomically normal non-immune hydrops and 8%
      of all cases, of non-immune hydrops presenting to this hospital over 15 years.
      False positive signal was seen in an additional three cases, using biotinylated
      probes. Digoxigenin labelled probes gave greater specificity and permitted
      detailed investigation of tissues high in endogenous biotin. Though most cells
      containing B19 DNA colabelled as erythroid precursors, viral DNA was frequently
      detected within mononuclear-phagocytic cells. In three cases viral signal was
      also found within occasional myocardial cells labelled by antibody to desmin.
      CONCLUSIONS: A relatively high proportion of cases of anatomically normal, non
      immune hydrops are caused by B19 infection. Digoxigenin is a more reliable probe
      label than biotin for in situ hybridisation in archival fetal tissues. Double
      labelling for cellular antigens and viral nucleic acid is a powerful technique
      for investigating virus-host cell interactions, and provides evidence that cell
      types other than those of erythroid lineage may have a role in human fetal
      parvovirus infection.

PMID- 1401176
TI  - Glutathione S-transferases in neonatal liver disease.
AB  - AIMS: To investigate the distribution of alpha and pi class glutathione S
      transferases (GST) in normal fetal, neonatal, and adult liver; and to examine
      changes in GST expression in neonatal liver disease. METHODS: alpha and pi class
      GST were immunolocalised in sections of formalin fixed liver tissue obtained from
      human fetuses (n = 21), neonates (n = 8), young children (n = 9) and adults (n =
      10), and from neonates with extrahepatic biliary atresia (n = 15) and neonatal
      hepatitis (n = 12). Monospecific rabbit polyclonal antibodies were used with a
      peroxidase-antiperoxidase method. RESULTS: Expression of pi GST was localised
      predominantly within biliary epithelial cells of developing and mature bile ducts
      of all sizes from 16 weeks' gestation until term and in neonatal and adult liver.
      Coexpression of pi and alpha GST was seen in hepatocytes of developing fetal
      liver between 16 and 34 weeks' gestation. Although pi GST was seen in occasional
      hepatocytes up to six months of life, this isoenzyme was not expressed by
      hepatocytes in adult liver. By contrast, alpha GST continued to be expressed by
      hepatocytes in adult liver; this isoenzyme was also seen in some epithelial cells
      of large bile ducts in adult liver. No change was observed in the distribution of
      alpha GST in either neonatal hepatitis or extrahepatic biliary atresia. However,
      aberrant expression of pi GST was identified in hepatocytes of all but one case
      of extrahepatic biliary atresia but in only two cases of neonatal hepatitis.
      CONCLUSIONS: The phenotypic alterations noted in extrahepatic biliary atresia may
      result from the effect of cholate stasis. Evaluation of the pattern of pi and
      alpha GST distribution by immunohistochemical staining may provide valuable
      information in distinguishing between these two forms of neonatal liver disease.

PMID- 1401177
TI  - Adenovirus infection of the large bowel in HIV positive patients.
AB  - AIMS: To describe the microscopic appearance of adenovirus infection in the large
      bowel of human immunodeficiency virus (HIV) positive patients with diarrhoea.
      METHODS: Large bowel biopsy specimens from 10 HIV positive patients, eight of
      whom were also infected with other gastrointestinal pathogens, with diarrhoea
      were examined, together with six small bowel biopsy specimens from the same group
      of patients. Eight of the patients had AIDS. The biopsy specimens were examined
      by light microscopy performed on haematoxylin and eosin stained and
      immunoperoxidase preparations, the latter using a commercially available antibody
      (Serotec MCA 489). Confirmation was obtained with electron microscopy. RESULTS:
      The morphological appearance of cells infected with adenovirus showed
      characteristic nuclear and cellular changes, although the inflammatory reaction
      was non-specific. Immunoperoxidase staining for adenovirus was sensitive and
      specific, and the presence of viral inclusions consistent with adenovirus was
      confirmed by electron microscopy. CONCLUSIONS: The light microscopic features of
      adenovirus infection are distinctive and immunocytochemistry with a commercially
      available antibody is a sensitive and specific means of confirming the diagnosis.
      Further studies of the role of adenovirus in causing diarrhoea in these patients
      are indicated.

PMID- 1401178
TI  - Detection of hepatitis B pre-core mutant by allele specific polymerase chain
      reaction.
AB  - AIM: Development of a specific polymerase chain reaction (PCR) assay for
      detection of the pre-core, stop codon, mutant of hepatitis B virus (HBV).
      METHODS: PCR primers, specific at the 3'-end for nucleotide 1896 of either the
      pre-core, stop codon, mutant or wild type HBV, were synthesised using published
      sequence data. Positive control templates for both types of virus were
      synthesised by the PCR, incorporating sequences specific for each virus type at
      the appropriate position. These templates were used to optimise the specificity
      of the procedure. Formalin fixed, paraffin wax embedded human tissue from acute
      or fulminant HBV hepatitis from Hong Kong or Oxford was then investigated for
      presence of mutant or wild type virus. The HBV DNA was amplified from this tissue
      using a two step procedure, with an initial amplification phase followed by a
      second diagnostic phase on optimally diluted target DNA. RESULTS: Specific
      detection of mutant or wild type HBV was achieved. An important factor in
      determining specificity was the temperature of annealing, 70 degrees C proving to
      be highly specific. To overcome the inherent variation of target copy number in
      clinical samples and to provide an intrinsic positive control, it was important
      to generate and standardise the amount of target HBV used for the specific PCR.
      Two cases of fulminant hepatitis and four cases of acute hepatitis from Hong
      Kong, and one case of fulminant hepatitis from Oxford, contained only wild type
      HBV, with no evidence of a mutant virus. CONCLUSION: This method can be applied
      to FFPE tissues. It is rapid, non-radioactive, and specific for the stop codon
      mutation at nucleotide 1896 of HBV. Preliminary investigation of a small number
      of cases of fulminant hepatitis from Oxford and Hong Kong showed only wild type
      virus. The result differs from results published from Japan and Israel.

PMID- 1401179
TI  - Relative usefulness of electron microscopy and immunocytochemistry in tumour
      diagnosis: 10 years of retrospective analysis.
AB  - AIMS: To determine retrospectively the relative usefulness of electron microscopy
      and immunocytochemistry for tumour diagnosis; to monitor the influence of new
      antibodies and antisera on the use of these techniques in one laboratory.
      METHODS: During 1980 to 1989 inclusive, 726 tumours were examined by electron
      microscopy, 862 by immunocytochemistry, and 286 by both techniques. The choice of
      techniques and, for immunocytochemistry, the range of antibodies used were
      compared between each category of final diagnosis. RESULTS: During the study
      period there was a sharp fall in the use of electron microscopy and a
      corresponding rise in immunocytochemistry. These trends applied to all categories
      of final tumour diagnosis, but the use of electron microscopy was sustained
      longer for lesions suspected or eventually confirmed to be melanomas or amine
      precursor uptake decarboxylation cell carcinoma (APUDomas)--for example,
      carcinoid tumours. The immunocytochemistry:electron microscopy use ratios ranged
      from 2.07:1 to 0.44:1 for the categories in which lymphoma and APUDoma,
      respectively, were the final diagnoses. The abandonment of electron microscopy
      for suspected or confirmed lymphomas and carcinomas corresponded to the
      increasing availability of relevant antisera and antibodies. CONCLUSIONS: The
      wider application of immunocytochemistry for tumour diagnosis is endorsed, but
      electron microscopy should be retained for selected cases in which the results of
      immunocytochemistry might be predictably ambiguous or otherwise unhelpful.

PMID- 1401180
TI  - Distinction between aleukaemic prodrome of childhood acute lymphoblastic
      leukaemia and aplastic anaemia.
AB  - AIMS: To document the features of the so-called aplastic presentation of
      childhood acute lymphoblastic leukaemia (ALL) and to determine whether this
      prodrome can be distinguished from aplasia. METHODS: The peripheral blood and
      bone marrow appearances of all cases of childhood ALL presenting in one health
      region of England in 13 years and eight months were reviewed. All cases
      presenting with cytopenia without circulating blasts and marrow aspirates with no
      infiltrate of blasts were studied in detail. RESULTS: Four of 305 (1.3%) children
      presented in this way. All four had reticulin fibrosis and increased cellularity
      in all or part of the marrow biopsy specimen. All were girls. Three had common
      and one surface membrane immunoglobulin positive ALL. Reassessment of this
      prodrome, by combining the features of four previously reported series of similar
      cases with the present one, highlighted the female preponderance (19 of 22
      cases), bone marrow fibrosis (10 of 11 evaluable cases), prominent bone marrow
      lymphocytes (14 of 22 cases) and temporary recovery (all 12 evaluable cases). Six
      of 14 evaluable cases had bone marrow biopsy specimen appearances of apparently
      uniform hypocellularity, but only one of these did not have fibrosis.
      CONCLUSIONS: If, in addition to an aspirate, a bone marrow trephine biopsy is
      carried out the prodrome can be distinguished from aplasia in most cases. The
      similarity of this prodrome to aplastic anaemia is merely superficial. Clinicians
      and morphologists may fail to appreciate the implications of this mode of
      presentation if the term "aplastic" continues to be used to describe this
      aleukaemic prodrome of ALL.

PMID- 1401181
TI  - The cause of turbidity in lyophilised plasmas and its effects on coagulation
      tests.
AB  - AIMS: To investigate the cause of turbidity in reconstituted lyophilised plasmas
      and to determine its effect on coagulometers. METHODS: The turbidities of 20
      normal plasmas and 16 reconstituted lyophilised plasmas were determined by
      comparing a 1 in 4 dilution in distilled water with a standard suspension in an
      Aminco Fluorocolorimeter (American Instrument Co) in nephelometric mode. The
      turbidities of five other plasmas were determined before and after
      lyophilisation. The turbid components of fresh and reconstituted lyophilised
      plasmas were studied using electron microscopy. The effects of turbidity on five
      types of coagulometer were determined by adding varying concentrations of a
      turbidity enhancing material. RESULTS: Reconstituted lyophilised plasmas were
      more turbid than normal plasmas, because of agglomerated liposomes. Serum
      depleted of chylomicrons and very low density lipoproteins was not rendered more
      turbid by lyophilisation. Three out of five types of automated coagulometer
      tested gave activated partial thromboplastin times which were appreciably
      affected by plasma turbidity. One of the instruments was unable to detect a clot
      in a moderately turbid plasma. A second instrument gave results which were
      significantly affected by turbidity. Turbidity of the substrate plasma did not
      affect specific factor VIII assays in two types of coagulometer. CONCLUSIONS:
      Lyophilisation of plasma induces turbidity due to the agglomeration of lipids.
      Such turbidity can affect the results of coagulation tests. Suppliers of
      lyophilised plasmas should be aware of this problem.

PMID- 1401182
TI  - Factors affecting the maintenance dose of warfarin.
AB  - AIM: To identify the possible factors determining the dose of warfarin prescribed
      in patients receiving anticoagulant treatment. METHODS: The computerised records
      of 2305 patients maintained on the drug in seven hospitals were amalgamated and
      classified into one of seven diagnostic groups. The associations with the dose of
      warfarin prescribed were investigated by univariate and multiple regression
      analysis. Differences between hospitals were studied with regard to the
      coagulometric method and the thromboplastin preparation used. RESULTS: The
      geometric mean dose of warfarin was 4.57 mg and 5% of patients were prescribed 10
      mg or greater. There was a noticeable decrease in dose with increasing age, which
      averaged about 6 mg for patients aged 30 but 3.5 mg for those aged 80. Men
      required slightly more warfarin than women. Patients with heart disease or atrial
      fibrillation required lower doses of warfarin, while higher doses were required
      by patients with deep vein thrombosis. Significant differences in mean warfarin
      dose among the seven hospitals were evident. These differences could not be
      explained entirely by the use of different coagulometric methods or
      thromboplastins. CONCLUSIONS: Clinicians should be aware that older patients need
      reduced doses of warfarin. The considerable differences in doses of warfarin
      among hospitals indicates that further efforts to improve uniformity are
      required.

PMID- 1401183
TI  - Survey of oral anticoagulant treatment in children.
AB  - AIMS: To find out which children are treated with oral anticoagulants and how
      their treatment is controlled in the United Kingdom. METHODS: Two questionnaires
      were used. The first was sent to general haematologists and the other to
      paediatric cardiologists and cardiac surgeons. RESULTS: There were 273 (58%)
      replies to the first questionnaire. Most children were treated because of
      artificial cardiac valve replacement. The mean target International Normalised
      Ratio (INR) used was 2.73 to 4.0 for children with heart valves and 2.1 to 3.25
      for children with venous thrombosis. The second questionnaire elicited replies
      from 11 of 22 cardiac centres. The mean target INR used for children with cardiac
      valves ranged from 2.59-3.77. Of 68 children covered in the survey, there have
      been two major bleeds and two thrombotic episodes: 78.8% of children were
      controlled with a venous prothrombin time and 21.2% with a capillary test. There
      was no consistency in the dose regimens used for the induction of oral
      anticoagulant treatment with warfarin. CONCLUSIONS: The levels of anticoagulation
      used for maintenance are similar to those recommended by the British Society for
      Haematology for adults (3.0 to 4.5). They seem to be safe for children too.

PMID- 1401185
TI  - Mycobacterium tuberculosis: a continuing cause of sudden and unexpected death in
      west London.
AB  - AIMS: To describe the pathological and background features of several cases of
      tuberculosis diagnosed at post mortem examinations and performed on behalf of HM
      Coroner over a three year period in west London. METHODS: Postmortem examinations
      were carried out by two pathologists working at hospital and public mortuaries in
      west London. Cases of tuberculosis were provisionally diagnosed on gross
      examination and the diagnosis confirmed on haematoxylin and eosin and Ziehl
      Neelsen staining of retained tissues. The background information was obtained by
      scrutinising hospital records and by direct enquiry to general practitioners by
      coroners' officers. RESULTS: Thirteen cases of pulmonary tuberculosis were
      diagnosed during the period. No other cause of death was found. The incidence of
      fatal pulmonary tuberculosis was 0.28% of coroners' necropsies in the study
      region. Cases had been referred to the coroner because death had occurred
      unexpectedly, or because no recent medical attention had been sought. Most cases
      arose among the elderly Asian immigrant population or the homeless or the
      alcoholic, or both. In 10 cases the macroscopic findings strongly indicated
      pulmonary tuberculosis and in the other three the diagnosis was considered to be
      a differential diagnosis. CONCLUSIONS: These findings have important health
      implications for those carrying out post mortem examinations from these groups as
      well as for those involved with the continuing care of immigrant or vagrant
      populations.

PMID- 1401184
TI  - Diagnostic tests for Helicobacter pylori: comparison and influence of non
      steroidal anti-inflammatory drugs.
AB  - AIMS: To evaluate the efficacy of culture, histology, CLO-test, Helico-G and
      Pyloriset tests in diagnosing Helicobacter pylori in the presence or absence of
      non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: Of 134 patients studied,
      75 had taken NSAIDs. At endoscopy, biopsy specimens were taken for culture,
      histology, and CLO-test. Blood was also taken for enzyme linked immunosorbent
      assay (ELISA) (Helico-G) and latex agglutination (Pyloriset) tests. RESULTS: The
      sensitivity, specificity, and predictive values of histology and CLO-test,
      compared with culture, ranged from 90% to 97%, regardless of NSAID intake. In the
      59 patients not taking NSAIDs Helico-G had a sensitivity of 75% (p < 0.05) and a
      specificity of 61%; Pyloriset's sensitivity and specificity were, respectively,
      63% (p < 0.05) and 67%. In the 75 patients taking NSAIDs the sensitivity of
      Helico-G was 81% and its specificity 45% (p < 0.05); Pyloriset had a sensitivity
      of 61% (p < 0.05) and a specificity of 50% (p < 0.05). CONCLUSION: These findings
      suggest that H pylori is more reliably diagnosed by culture, histology, and CLO
      test than by the serological tests used in this study, especially in patients
      treated with NSAIDs.

PMID- 1401186
TI  - Staphylococcal toxins and sudden infant death syndrome.
AB  - AIMS: To investigate the hypothesis that commonly occurring bacterial toxins
      cause sudden infant death syndrome (SIDS) by (1), determining in which tissues
      bacterial toxins are concentrated after intravenous injection in rats; and (2),
      seeing if the same tissues contain detectable toxins in cases of SIDS. METHODS:
      The tissue distribution of intravenously injected staphylococcal enterotoxin A
      (SEA), enterotoxin B (SEB), enterotoxin C (SEC), enterotoxin D (SED), toxic shock
      syndrome toxin (TSST-1), and alpha-haemolysin was studied in rats using
      immunohistology and polyacrylamide gel electrophoresis with immunoblotting.
      Immunostaining was also carried out on formalin fixed kidneys from cases of SIDS
      and a comparison series of necropsy cases using anti-SEA, anti-SEB, anti-SEC2 and
      anti-SED. RESULTS: Immunohistology showed that SEB, SEC, SED and TSST-1 were all
      concentrated in the proximal convoluted tubular cells of the kidney. The presence
      of these toxins was confirmed in kidney homogenates using electrophoresis and
      immunoblotting. There was positive granular staining in the proximal convoluted
      tubular cells of the kidney in 36% of SIDS cases and 12% of the comparison series
      with anti SEC2 (chi 2 = 6; p < 0.025). CONCLUSION: SEC, or a bacterial toxin with
      epitopes in common, could have a pathogenic role in SIDS.

PMID- 1401187
TI  - Pulsed field gel electrophoresis on frozen tumour tissue sections.
AB  - The application of pulsed field gel electrophoresis (PFGE) to the molecular
      genetic analysis of solid tumours has been restricted by the requirement for
      whole single cells as a DNA source. A simple technique which allows for the
      direct analysis of histologically characterised solid tumour material by pulsed
      field gel electrophoresis was developed. Single frozen tissue sections obtained
      from colonic carcinoma specimens were embedded without further manipulation in
      molten, low melting temperature agarose. The tumour DNA contained within the
      agarose plug was subjected to restriction enzyme digestion and PFGE. Sufficient
      high molecular weight DNA is yielded by this method to obtain a hybridisation
      signal with a single copy probe. Histological examination of adjacent tissue
      sections may also be carried out, permitting correlation between molecular
      analysis and tumour histology.

PMID- 1401188
TI  - Has there been an information explosion in histopathology?
AB  - The numbers of papers published between 1966 and 1990 which could be of relevance
      to a histopathologist were assessed. The search for papers was conducted under 18
      medical subject headings using the CD-Plus Medline computerised database for the
      years 1966, 1978, 1982, 1986 and 1990. Between 1966 and 1990 16 categories showed
      an increase in the number of indexed papers and in 11 of these the increase was
      by over 200%. The two categories that showed a slight reduction were
      cytodiagnosis and polarisation microscopy. The total number of papers of probable
      relevance to histopathology in 1990 was 36,780, a 293% increase since 1966; this
      increase was greater than the increase in the total number of papers indexed
      (189%). The number of papers relevant to histopathology has increased
      dramatically in recent years and this increase has been proportionately greater
      than in some other areas of medicine.

PMID- 1401189
TI  - Pseudohyperphosphataemia in patients with multiple myeloma.
AB  - The phosphate concentrations were measured in 41 patients who had multiple
      myeloma with paraproteinaemia using four different methods to compare the
      incidence of pseudohyperphosphataemia. The direct acid/molybdate method produced
      the highest number of anomalous results. The erroneously high phosphate
      concentration was attributable to the presence of turbidity in the reaction
      mixture. No association was found between paraprotein type and occurrence of
      turbidity. The direct acid/molybdate method was unreliable in patients with serum
      paraproteins and should therefore not be used for the measurement of phosphate
      concentration in such patients.

PMID- 1401190
TI  - Expression of 120 kilodalton protein and cytotoxicity in Helicobacter pylori.
AB  - Antral biopsy culture supernatants from 14 subjects with chronic gastritis, known
      to have IgA antibodies to the 120 kilodalton protein, showed positive recognition
      of this antigen in western blots against a cytotoxin positive strain of
      Helicobacter pylori but gave negative reactions with two cytotoxin negative
      strains. Control immunoblots with culture supernatants from 13 non-responders to
      the protein were all negative. This indicates a direct association between
      expression of the 120 kilodalton protein in H pylori strains and cytotoxicity.

PMID- 1401191
TI  - Selected cryopreservatives for long term storage of Helicobacter pylori at low
      temperatures.
AB  - To meet the need for information on cryopreservation, a study was done on 32
      Helicobacter pylori strains, comparing different cryopreservative media. Sheep
      blood, horse blood, horse serum with and without glycerol, and mineral oil media
      were used for long term storage of H pylori at -70 degrees C or in liquid
      nitrogen. Procedures were developed which permitted recovery of 87.5% of the
      strains included in the study after they had been stored for 24 months. Of those
      strains stored for more than three years, 60% were recovered. It is concluded
      that most strains of H pylori can be stored for up to one year or longer, under
      refrigeration, at -70 degrees C or in liquid nitrogen.

PMID- 1401192
TI  - Successful freeze storage and lyophilisation for preservation of Helicobacter
      pylori.
AB  - Long term storage techniques for the preservation of Helicobacter pylori were
      developed. The cells survived at -75 degrees C in the presence of glycerol and at
      +4 degrees C after freeze-drying. Both techniques are suitable for routine use.

PMID- 1401193
TI  - A simple and direct method of turnround time audit in a microbiology laboratory.
AB  - A method of specimen turnround time audit, directly controlled by laboratory
      staff, was applied to a bacteriology service to assess service efficiency and
      identify delays and other deficiencies, so that resources could be optimised. The
      method provided a complete collection of turnround time data and was easy to use.
      Delays of both administrative and technical natures were identified, and with
      minimal reorganisation the mean turnround time was improved.

PMID- 1401194
TI  - Evaluation of modified passive haemagglutination assay for Vi antibody estimation
      in Salmonella typhi infections.
AB  - A simple passive haemmagglutination assay (PHA) was developed to detect Vi
      antibodies, to improve the diagnosis of typhoid fever by small laboratories. The
      Vi capsular antigen of Salmonella typhi was extracted by alternate alcohol and
      acetone precipitation. Formalin fixed, sheep red blood cells treated with
      chromium chloride were sensitised with this Vi antigen and antibodies detected
      and measured by PHA. The test had a sensitivity of 83.3% among 30 cases of
      typhoid fever confirmed by culture. The specificity of the test was 94%, making
      it suitable for use in laboratories without facilities for IFAT or ELISA.

PMID- 1401195
TI  - PIVKA-II concentrations in patients with cystic fibrosis.

PMID- 1401196
TI  - Modifying the request behaviour of clinicians.

PMID- 1401197
TI  - AgNOR technique in relation to colorectal neoplasia.

PMID- 1401198
TI  - Breast biopsy specimen fixation.

PMID- 1401199
TI  - Bone marrow trephine biopsy in lymphoproliferative disease.

PMID- 1401201
TI  - Early clinical pathologists: Edward Jenner (1749-1823)

PMID- 1401200
TI  - ACP Broadsheet 132: September 1992. Gross examination of the large intestine.

PMID- 1401202
TI  - Alveolar rhabdomyosarcoma infiltrating bone marrow at presentation: the value to
      diagnosis of bone marrow trephine biopsy specimens.
AB  - AIMS: To describe the histological appearances of bone marrow infiltrated with
      rhabdomyosarcoma at presentation and to determine their value in establishing the
      diagnosis. METHODS: Patients presenting over seven years in the northern health
      region of England with rhabdomyosarcoma were studied. Bone marrow aspirates and
      trephine biopsy specimens taken at presentation were examined. RESULTS: Seven of
      32 patients with rhabdomyosarcoma had bone marrow infiltration, resulting in
      marrow failure in all cases, at diagnosis. The diagnosis was established in these
      seven by the typical cytological appearances and immunophenotype of the
      infiltrating cells (all seven patients) and cytogenetic abnormalities (three
      patients). Histological examination of the bone marrow showed a pseudoalveolar
      pattern with fibrous septal bands, enlarged vascular channels, and lack of
      cohesion of the tumour cells within the subdivided aggregates in all seven. In
      four cases multinucleate giant cells, often with peripherally sited nuclei, were
      found. CONCLUSIONS: These histological features of infiltrated marrow are so
      characteristic that the diagnosis of alveolar rhabdomyosarcoma can be made, or at
      least suspected, in many cases even without recourse to technically difficult and
      expensive further investigations. Bone marrow biopsy should be a routine part of
      the investigation of patients with bone marrow failure and will be of particular
      value in the diagnosis of those with disseminated alveolar rhabdomyosarcoma.

PMID- 1401203
TI  - Use of paraffin wax embedded bone marrow trephine biopsy specimens as a source of
      archival DNA.
AB  - AIMS: To evaluate the use of DNA extracted from paraffin wax embedded trephine
      biopsy specimens as a source of archival nucleic acid for Southern hybridisation
      studies and polymerase chain reaction (PCR) amplification. METHODS: DNA was
      extracted simultaneously from paraffin wax embedded bone marrow trephine and
      lymph node biopsy specimens after incubation of tissue sections for one to five
      days in lysis mix and proteinase K with periodic sampling. DNA from 10 trephine
      biopsy specimens was subjected to PCR amplification using HLA-DPB primers to
      determine whether the extracted nucleic acid was of sufficient quality to permit
      amplification. RESULTS: For most specimens the greatest yield of high molecular
      weight DNA was seen after five days' incubation. Unlike lymph node material the
      quality of extracted nucleic acid and the quantity obtained from trephines was
      insufficient for Southern blot analysis. PCR amplification using HLA-DPB primers
      yielded positive results in six out of 10 trephine biopsy specimens. CONCLUSIONS:
      DNA extracted from paraffin wax embedded trephine biopsy specimens is largely
      degraded and unsuitable for Southern analysis but serves as a useful source of
      archival nucleic acid for PCR amplification.

PMID- 1401205
TI  - Improved PCR method for detecting monoclonal immunoglobulin heavy chain
      rearrangement in B cell neoplasms.
AB  - AIMS: To develop a simple, optimised, polymerase chain reaction (PCR) based
      method for detecting the rearranged immunoglobulin heavy chain (IgH). METHODS:
      Using as primers oligonucleotides (Fr2A, Fr2B) homologous to the conserved
      sequences to the framework II region and the joining (JH) region, 25 patients
      with B cell lymphoproliferative disorders, previously characterised by Southern
      blotting, and three patients with light chain myeloma were studied. RESULTS: The
      PCR product from a polyclonal B cell population showed a broad band when analysed
      on a 3% agarose gel; DNA from B cell lines and B lymphoproliferative disorders
      showed a discrete band. Specificity of the amplification was confirmed by cloning
      and sequencing the amplified product as well as by Southern blotting with an
      internal probe homologous to the framework 3 region. Primers Fr2A and Fr2B
      detected monoclonality in three patients with light chain myeloma, while primers
      directed against the FrIII region showed a polyclonal response. CONCLUSIONS:
      Deletions and extensive somatic mutations within the FrIII region may give false
      negative results with primers homologous to the region. A PCR using the method
      described, with a repertoire of primers homologous to the FrII and FrIII regions,
      will therefore increase the frequency of detection of monoclonality.

PMID- 1401204
TI  - Increased interleukin 6 concentrations in the absence and presence of HIV-1
      infection in haemophilia.
AB  - AIMS: To measure IL-6 concentrations in asymptomatic HIV-1 antibody positive and
      negative haemophilic patients and to correlate these with IgG concentrations and
      CD4 positive cell numbers. METHODS: IL-6 concentrations were measured by bioassay
      in stored serum from a prospective cohort of haemophilic patients in whom
      immunoglobulins and T cell subsets had been determined. Values of IL-6 and
      immunoglobulins were also correlated with severity of liver disease. RESULTS: IL
      6 concentrations were raised in haemophilic patients independent of HIV-1
      antibody status. In HIV-1 antibody positive patients there was no correlation
      between IL-6 concentrations and CD4 positive cell numbers, but there was a
      correlation with IgG (r = 0.4; p = 0.05). In HIV-1 antibody negative patients
      there were no significant correlations. CONCLUSIONS: Haemophilic patients have
      increased IL-6 concentrations; in HIV-1 positive patients this is independent of
      the decline in CD4 cell count. The raised concentrations do not correlate with
      the clinical severity of liver disease.

PMID- 1401206
TI  - Alpha-1 antitrypsin gene exon use in stimulated lymphocytes.
AB  - AIMS: To investigate the expression of mRNA transcripts containing exon A or B in
      lymphocyte cultures. METHODS: An in situ hybridisation technique, using
      synthetic, biotinylated oligonucleotide probes was deployed to allow the
      demonstration of exon A, exon B, or the normal hepatocyte message containing exon
      C. RESULTS: Lymphocytes used the same alternative splicing technique as monocytes
      in the generation of their alpha-1 antitrypsin message. They also provided data
      on the frequency of exon A and B expression in cells from different subjects.
      Most circulating granulocytes failed to show the alpha-1 antitrypsin message,
      suggesting that this protein is synthesised in the marrow and represents a stored
      protein component in polymorph and circulating nuclear lymphocytes. CONCLUSIONS:
      In situ hybridisation is a sensitive technique for the detection of individual
      gene exon use in cell populations. Lymphocytes show the same promoter use as that
      described for monocytes.

PMID- 1401207
TI  - Antibodies to choroid plexus in senile dementia of Alzheimer's type.
AB  - AIMS: To investigate whether autoantibodies to choroid plexus are present in
      human senile dementia. METHODS: Serum samples from 40 elderly people presenting
      with characteristic, diagnostic criteria of senile dementia of Alzheimer's type
      and 20 age matched healthy controls were tested by indirect immunofluorescence
      for the presence of autoantibodies to choroid plexuses, using frozen sections of
      rat or human fetal brain tissue. RESULTS: Significant labelling of choroid plexus
      basement membrane was observed in 17 of the 40 samples from patients with senile
      dementia; in the control series one sample of rat but not human plexus labelled
      positively (p < 0.01). CONCLUSIONS: The antibodies identified in this series of
      patients with Alzheimer's disease suggest that autoimmune mechanisms might be
      responsible for some of the changes in cerebrospinal fluid production described
      in this disorder.

PMID- 1401208
TI  - Collagenous colitis: jejunal and colorectal pathology.
AB  - AIMS: To determine: (1) whether there is an association between collagenous
      colitis and coeliac disease or lymphocytic colitis; (2) the distribution of
      lymphocyte subsets and macrophages in the lamina propria and surface epithelial
      layer in collagenous colitis; and (3) the colorectal distribution of the disease
      and whether a mucosal biopsy specimen, using a flexible sigmoidoscope, is
      sufficient to diagnose it. METHODS: The clinical data and colorectal biopsy
      specimens from 38 patients with collagenous colitis were studied. In 10, small
      bowel biopsy specimens were also available for review. Immunostaining of the
      mucosal lymphoid infiltrate with a panel of relevant antibodies was carried out
      on formalin fixed tissue in seven cases; in three the phenotyping was performed
      on fresh biopsy specimens separately frozen or fixed in B5 solution. RESULTS:
      Coeliac disease was found in four out of the 10 patients with collagenous colitis
      who had had a small bowel biopsy, in contrast to the prevalence of the disease in
      Australia of 1 in 3000. Collagenous colitis did not respond to gluten withdrawal.
      Five of 29 (17%) of the patients had a mixed pattern of lymphocytic and
      collagenous colitis. Immunostaining of the lymphoid infiltrate showed that the
      striking increase in intraepithelial lymphocytes in collagenous colitis was due
      to an influx of CD8 positive cells. The occurrence and severity of collagenous
      colitis along the large bowel were independent of the anatomical site, and in
      more than 90% of cases biopsy specimens from the sigmoid colon or rectum were
      diagnostic. CONCLUSIONS: There is a very high incidence of coeliac disease among
      patients with collagenous colitis so that jejunal biopsy should be an essential
      part of their investigations, especially if symptoms persist. However, only a
      minority showed a mixed pattern of lymphocytic and collagenous colitis. The
      intraepithelial lymphocytes in collagenous colitis are CD8 positive cells.
      Collagenous colitis can be diagnosed from rectal or sigmoid colon biopsy
      specimens in more than 90% of cases.

PMID- 1401209
TI  - Immunohistological study of intrahepatic expression of hepatitis B core and E
      antigens in chronic type B hepatitis.
AB  - AIMS: To study the intrahepatic expression of hepatitis B virus (HBV)
      nucleocapsid antigen; and to determine the differential distribution of hepatitis
      B core and E antigens in chronic hepatitis B. METHODS: Hepatocyte expression of
      HBV nucleocapsid antigen was studied using rabbit anti-HBc, directed against both
      HBcAg and HBeAg; differential distribution of HBcAg and HBeAg was studied using
      murine monoclonal anti-HBc and anti-HBe in 120 patients with chronic hepatitis B.
      RESULTS: HBV nucleocapsid antigen was detected in 14 of 16 (87.5%) HBeAg
      seropositive patients with chronic persistent hepatitis (CPH), and in 54 of 64
      (84.4%) HBeAg seropositive patients with chronic active hepatitis (CAH). Nuclear
      expression of nucleocapsid antigen was more prevalent in patients with CPH than
      in those with CAH; this was reversed in terms of exclusive cytoplasmic expression
      of nucleocapsid antigen (p < 0.05). Of 45 patients with nucleocapsid antigen in
      the nucleus, samples from 44 (97.8%) and 17 (37.8%) stained positively with
      monoclonal anti-HBc and anti-HBe, respectively. Of 65 patients with cytoplasmic
      nucleocapsid antigen, samples from 61 (93.8%) and 57 (87.7%) stained positively
      with monoclonal anti-HBc and anti-HBe, respectively. CONCLUSIONS: HBV
      nucleocapsid antigen is more prevalent in HBeAg positive patients with CPH than
      in those with CAH. Cellular expression of HBcAg and HBeAg in the cytoplasm is
      more or less the same; in the nucleus HBcAg exceeds HBeAg expression.

PMID- 1401210
TI  - Quantitative assessment of histological changes in chronic gastritis after
      eradication of Helicobacter pylori.
AB  - AIMS: To evaluate the effect of 10 day triple treatment on H pylori eradication
      and associated gastritis. METHODS: Fifty patients with H pylori positive non
      ulcer dyspepsia were treated for 10 days with amoxicillin, tinidazole, and
      bismuth salts. Histological examination of the antral mucosa was performed before
      (T0), six weeks (T1), and six months (T2) after treatment. The new Sydney
      classification of gastritis was used, using a score from 0 to 3 to grade degree
      of inflammation, atrophy, activity (intraepithelial or lamina propria damage) and
      H pylori. RESULTS: At T0 all patients had chronic active gastritis. Lymphoid
      follicules were present in 12 cases. At T1 33 patients were H pylori negative:
      the score showed a decrease of activity (from 2.5 to 0.54). The result was
      confirmed at T2 (mean score 0.22). Inflammation decreased from 1.8 to 1.4 at T2.
      Only one case of follicular gastritis was observed. In H pylori positive patients
      the scores did not show significant modifications. CONCLUSIONS: Ten day triple
      treatment is effective in eradicating H pylori in 69% of cases, causing a
      decrease of the total score for gastritis. Activity, defined by polymorph
      infiltration, was promptly reduced when H pylori was eradicated. There was a
      trend to a reduction in inflammation, but atrophy was irreversible.

PMID- 1401211
TI  - Lethal synergistic action of toxins of bacteria isolated from sudden infant death
      syndrome.
AB  - AIM: To test the hypothesis that lethal toxins of bacteria associated with sudden
      infant death syndrome (SIDS) can act synergistically. METHODS: Bacteria occurring
      together in the nasopharynx of cases of cot death were studied. The lethal
      toxicity of crude toxin preparations was determined over a range of dilutions by
      injections into the chorioallantoic vein of the chick embryo. Toxin preparations
      of low lethality for the chick embryo SIDS model were then tested in combination.
      RESULTS: Staphylococcus aureus toxin preparations showed low lethality when
      tested alone, even at low dilution. At 1 in 100 dilution S aureus toxin was
      lethal to one out of 15 chick embryos. Escherichia coli toxin preparations showed
      high lethality except on high dilution (1 in 80) when lethality fell to two out
      of 15 of chick embryos. When the same toxin preparations were tested
      simultaneously in combination, lethality rose to 14 out of 15. Similar findings
      were observed over a range of toxin dilutions. This finding was highly
      significant (p = 0.0012). CONCLUSIONS: That synergy between toxins can enhance
      the lethality of toxins elaborated by bacteria associated with SIDS.

PMID- 1401213
TI  - Fungal infections of the small and large intestine.
AB  - AIMS: To study the pathological features of fungal infections affecting the lower
      intestinal tract (duodenum, small and large bowels). METHODS: Between mid-1981
      and mid-1991, 14 cases of deep mycotic infections affecting the lower intestinal
      tract were found among 890 consecutive necropsies on patients with malignant
      disease treated in a regional cancer centre (incidence 1.6%). These 14 cases
      accounted for 54% of all gastrointestinal fungal infection detected. The relevant
      clinical, necropsy, histological and microbiological data were reviewed. RESULTS:
      Candida spp and Aspergillus spp accounted for all infections. The macroscopic
      appearances included ulcers of varying configuration, mucosal flecks, sloughed
      mucous membranes, polypoid masses and segmental lesions. Either organism could
      produce this range of lesions, but Candida tended to have a mucosal location and
      Aspergillus was associated with transmural invasion. Combined infections showed
      Candida in the surface mucosa and Aspergillus hyphae in submucosal vessels with
      spread into the bowel wall in a radiating pattern. During the final illness,
      gastrointestinal symptoms and signs were often slight and microbiological
      investigations were unhelpful. CONCLUSIONS: Variable gross appearances are
      relevant for endoscopists, particularly lesions which resemble pseudomembranous
      colitis. Endoscopic biopsy specimens may have a role in antemortem diagnosis.
      Failure to diagnose these infections during life emphasises the importance of
      necropsy in the clinicopathological audit of deaths in this group of patients.

PMID- 1401212
TI  - Possibility of separating toxins from bacteria associated with sudden infant
      death syndrome using anion exchange chromatography.
AB  - AIMS: To develop techniques for the characterisation of toxins elaborated by a
      strain of Escherichia coli associated with sudden infant death syndrome (SIDS).
      METHODS: E coli SIDS 04, isolated from the nasopharynx of a case of SIDS, was
      studied. Cell-free toxin preparations were standardised, their protein measured,
      and analytical separation of proteins achieved using sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE). Acetone precipitation of proteins
      was required prior to Coomassie blue staining of bands. Preparative separation
      was achieved on an anion exchange column using a programmed concentration
      gradient of NaCl in TRIS buffer. Fractions were tested individually or pooled for
      presence of lethal toxin including endotoxin. Lethal toxin was detected with the
      chick embryo test system. Endotoxin was measured using a chromogenic modification
      of the Limulus amoebocyte assay. RESULTS: Twenty one peaks were detected by
      chromatography. Ten individual, or pooled, fractions were assayed for endotoxin
      which ranged from 27-33 pg/ml. Much greater variation was found when the same
      fractions were assayed in chick embryos. E coli fractions varied considerably in
      lethal toxicity, from 0/10 to 10/10 chick embryos killed/tested. Certain E coli
      fractions tested individually (lethality four out of 10 to eight out of 10)
      proved more lethal (10 out of 10) if pooled prior to testing. CONCLUSIONS: In E
      coli infection associated with SIDS relatively low concentrations of
      extracellular protein are lethally toxigenic for the chick embryo model of SIDS.
      These proteins can be separated analytically by SDS-PAGE and preparatively by
      anion exchange chromatography. Toxicity of individual fractions is not correlated
      with endotoxin concentrations in samples tested.

PMID- 1401214
TI  - New selective medium for isolating Clostridium difficile from faeces.
AB  - AIMS: To compare CCFA (cycloserine, cefoxitin fructose agar) with a new selective
      medium CDMN (containing cysteine hydrochloride, norfloxacin, and moxalactam) for
      the isolation of Clostridium difficile after direct faecal culture. METHODS: The
      minimum inhibitory concentration (MIC) of norfloxacin was determined for 64
      strains of C difficile, 17 strains of other Clostridium sp, and 66 various
      isolates of faecal origin, together with MIC determinations of moxalactam against
      the 81 strains of Clostridium sp and 15 isolates of Bacteroides sp. Using C
      difficile agar base with 0.5 g/l of cysteine hydrochloride, norfloxacin and
      moxalactam were incorporated into the medium and compared with CCFA for the
      isolation of C difficile after direct faecal culture. RESULTS: Norfloxacin (12
      mg/l) inhibited the growth of enterobacteriaceae and faecal streptococci;
      moxalactam (32 mg/l) inhibited the growth of most strains of Bacteroides sp
      tested, together with Clostridium sp other than C difficile. Using the
      antibiotics in combination (CDMN), the growth and colonial morphology of 64
      strains of C difficile were unaffected. When CDMN medium was compared with CCFA
      for the isolation of C difficile from 832 faeces from inpatients with diarrhoea,
      the CDMN agar isolated 20% more strains and reduced the number of contaminating
      colonies by 30%. CONCLUSIONS: CDMN both improves the isolation rate of C
      difficile from faecal specimens and reduces the growth of other organisms
      compared with CCFA.

PMID- 1401216
TI  - Plasma total thyroxine and free thyroxine concentrations in congenital
      hypothyroidism before and during treatment.
AB  - AIMS: To examine the relation between plasma total thyroxine and free thyroxine
      in children with congenital hypothyroidism. METHODS: Regression analysis was
      performed on 114 cases on the paired total thyroxine and free thyroxine
      measurements taken from the same blood sample. Conversion equations were derived
      using structural relation models. RESULTS: A linear relation was found between
      log total thyroxine and log free thyroxine values. The regression slopes for
      values taken before treatment and values taken while patients were receiving
      replacement treatment were significantly different. CONCLUSIONS: The data suggest
      that there is a close association between total and free thyroxine in congenital
      hypothyroidism, but that the relation is changed by thyroid replacement
      treatment.

PMID- 1401215
TI  - Comparison of Sentinel and Bactec blood culture systems.
AB  - AIMS: To evaluate the Sentinel automated blood culture system and to compare its
      performance with that of Bactec. METHODS: The Sentinel blood culture system was
      evaluated in three centres. The performance of the system was assessed in
      comparison with the routine blood culture method used in these centres, the
      Bactec system. RESULTS: Blood culture sets (n = 2180) consisting of Sentinel
      aerobic and anaerobic, and Bactec aerobic and anaerobic bottles yielded 218 (10%)
      clinically important isolates. One hundred and fifty five (71%) of the isolates
      were detected by both systems; 35 (16%) were detected by Sentinel only; and 28
      (13%) by Bactec only. For the duration of the evaluation, the Sentinel system was
      deliberately configured so that it was impossible to detect positive results
      during the first 12 hours. The times to positivity after the first 12 hours were
      similar. Data gathered during and subsequent to the evaluation have been used by
      the manufacturer to refine the algorithm so that positive results can be detected
      at a minimum of 2.25 hours. CONCLUSIONS: After a period of familiarization the
      Sentinel system was considered easy to use. Sentinel is a useful addition to the
      methods available for the detection of bacteria in blood cultures.

PMID- 1401217
TI  - Nocardia infection in AIDS: a clinical and microbiological challenge.
AB  - A case of Nocardia asteroides pneumonia was diagnosed after death in a patient
      with AIDS. Six sputum cultures and one bronchoalveolar lavage fluid contained no
      pathogens, and no growth was obtained from one pleural fluid aspirate. None of
      these specimens was incubated for more than two days. Extended incubation for
      mycobacteria also failed to help in the diagnosis. N asteroides was isolated from
      pus taken from the lung cavity during the post mortem examination. It is
      suggested that if nocardiosis enters the differential diagnosis all specimens
      should be cultured for at least two weeks and the use of selective media be
      considered. This case highlights the need for clinicians to maintain a high index
      of suspicion for this pathogen.

PMID- 1401218
TI  - Sarcoidosis: association with small bowel disease and folate deficiency.
AB  - A 30 year old woman with recurrent anaemia due to folate deficiency had evidence
      of sarcoid granuloma on small bowel biopsy but was presumed to have Crohn's
      disease. The diagnosis of small bowel sarcoidosis was not seriously considered
      until she developed systemic manifestations of sarcoidosis (cutaneous and
      pulmonary lesions) over the following 20 years. Sarcoidosis of the
      gastrointestinal tract, particularly the small bowel, is rare and this case is
      unusual because bowel pathology preceded more generalised lesions. As far as is
      known it is also the first case to be described presenting with malabsorption of
      folic acid.

PMID- 1401219
TI  - Immunoperoxidase techniques and histology in the diagnosis of rhabdomyolysis
      related acute renal failure.
AB  - A case of rhabdomyolysis associated acute renal failure (RM-ARF) occurring as a
      result of strenuous exercise is presented. Diagnostic renal biopsy was performed.
      The histological appearances, combined with immunoperoxidase staining for
      myoglobin, allowed a positive diagnosis of RM-ARF to be made and excluded the
      possibility of glomerulonephritis. The patient recovered completely after a
      stormy clinical course.

PMID- 1401220
TI  - Gonadoblastoma and fertility.
AB  - Most patients with gonadoblastoma have dysgenetic gonads. This rare tumour has
      been described in three pregnant women. A fourth case in a 26 year old pregnant
      woman who presented with gonadoblastoma and dysgerminoma, is reported. She had a
      normal term pregnancy, 46XX chromosomes, normal genitalia, no history of
      menstrual irregularities and no signs of hyperandrogenism, thereby differing from
      the other reported cases. The germ cell component of this patient's tumour had
      undergone rapid overgrowth, most of the tumour comprising pure dysgerminoma. It
      is suggested that gonadoblastoma may occur in functionally and morphologically
      normal gonads more often than previous case reports imply.

PMID- 1401222
TI  - Systemic amyloidosis of beta 2 microglobulin type.
AB  - A patient receiving haemodialysis for 15 years developed systemic amyloidosis of
      beta 2 microglobulin type. Noticeable deposits of amyloid were present in the
      myocardium, intervertebral discs, joint cartilages and tendons. Less conspicuous
      amounts were present in blood vessel walls in the lungs, liver, adrenal glands
      and brain, and within the stroma of the prostate, testis and kidney, often with
      foci of calcification.

PMID- 1401221
TI  - Bone marrow necrosis at transformation of chronic granulocytic leukaemia treated
      with interferon.
AB  - A patient with chronic myeloid leukaemia was treated with interferon without
      using conventional cytotoxic agents. Bone marrow necrosis developed at the onset
      of blast transformation. It is suggested that cytotoxic drugs should be given
      before treatment with interferon for chronic myeloid leukaemia. Cytotoxic drugs
      may also be needed to prevent rapid bone marrow growth once interferon has been
      withdrawn.

PMID- 1401223
TI  - Histological reclassification of 101 intraoral salivary gland tumours (new WHO
      classification).
AB  - The epithelial salivary gland tumours have for many years been categorised
      according to the 1972 World Health Organisation (WHO) classification. In 1990 a
      proposed revision of this classification was elaborated. In this study 101
      intraoral salivary gland tumours were reclassified accordingly. In 29 of the
      cases the original histological diagnosis was changed, which in most cases,
      occurred in the benign or malignant tumour groups. In seven cases the diagnosis
      was changed from benign to malignant or vice versa. The results of this study
      show that the histological classification of intraoral salivary gland tumours
      remains difficult, even when applying the new WHO classification.

PMID- 1401224
TI  - New enzyme immunoassay for detecting cryptococcal antigen.
AB  - Results obtained with a recently introduced enzyme immunoassay system (EIA) for
      the detection of cryptococcal antigen (Meridian Diagnostics Inc) were compared
      with those obtained by a latex agglutination (LA) method (Immuno-Mycologics,
      Norman, Oklahoma, USA). Fifty four samples were examined. There was 92% agreement
      between the two methods. One false positive result was obtained with LA, and one
      sample was inevaluable. The EIA was rapid and simple to perform. There was some
      evidence that it gave fewer false positive reactions and improved the diagnosis
      of genuine early cases.

PMID- 1401225
TI  - Selective criteria for the microbiological examination of faecal specimens.
AB  - To assess the effectiveness of predetermined investigation criteria for the
      examination of faecal samples from inpatients, cultured stool specimens were
      prospectively examined for Salmonella spp, Shigella spp, Campylobacter spp and
      Clostridium difficile, and screened microscopically for intestinal parasites. Out
      of a total of 505 specimens, 421 (83%) fulfilled the criteria for examination for
      C difficile, 254 (50%) for Salmonella spp, Shigella spp, and Campylobacter spp,
      and 87 (17%) for intestinal parasites. Isolation rates for these organisms in
      those groups of patients where examination was indicated were 22.5% for C
      difficile and 9.1% for Salmonella spp, Shigella spp, and Campylobacter spp; the
      detection rate for parasites was 3.5%. In those patients where the criteria did
      not suggest investigation, the isolation or detection rates were 3.6% for C
      difficile, 0% for Salmonella spp, Shigella spp, and Campylobacter spp, and 1.7%
      for intestinal parasites, suggesting that the use of predetermined investigation
      criteria was effective.

PMID- 1401226
TI  - Diffuse axonal injury caused by assault.
AB  - The case reports of 50 fatal head injuries caused by assault and managed at the
      Institute of Neurological Sciences, Glasgow, were reviewed. Fifteen cases had
      diffuse axonal injury. Diffuse axonal injury is a well recognised type of brain
      damage brought about by a head injury, usually as a result of a road traffic
      accident or fall from a height. It does not seem to be widely appreciated that it
      may also occur as a result of an assault. This has important medicolegal
      implications.

PMID- 1401227
TI  - Auditory comprehension of "yes-no" questions by adult aphasics.
AB  - Two groups of adult aphasics were administered four different types of auditory
      verbal "yes-no" questions. One group received questions including egocentric,
      environmental, pictorial, and relationship items in a consistent order. The
      second group received the same questions in random order. Support was found for
      the existence of a hierarchy of difficulty among the types of auditory-verbal
      "yes-no" questions. There was no significant difference between the two groups'
      performance even though the consistent presentation group was slightly superior
      to the random order group on the auditory-verbal "yes-no" questions.

PMID- 1401228
TI  - A review and critical analysis of treatment research related to articulation and
      phonological disorders.
AB  - This article contains a summary of aspects of research designs and strategies
      found in 63 published reports in which the effectiveness of treatment of
      articulation or phonological disorders was evaluated. These research reports were
      published in four nationally refereed journals that contained most of the
      literature published in the decades of the 1970s and 1980s. A total of 91 items
      were evaluated in each report by two reviewers working independently, including
      types of research designs, details about subjects, sampling, and types of
      independent and dependent variables used by researchers. Comparisons were made
      within each decade and across both decades to identify strengths and limitations.
      Some significant differences in research designs and variables under
      investigation occurred between the decades. A critical analysis was performed,
      and suggestions for changes are discussed.

PMID- 1401229
TI  - Assessment of sensitivity to interpersonal stress in stutterers.
AB  - The Willoughby Personality Schedule-R was administered to adult male Yugoslav
      stutterers who were not yet in treatment. Internal consistency of the WPS-R was
      assessed by computing item-scale score correlations. Twenty-two of 25 items were
      significantly correlated with WPS-R total score. Confirmatory factor analysis
      revealed three separate and reliable dimensions: Social Isolation (ssca .85),
      Social Confidence (ssca .74), and Social Sensitivity (ssca = .62), that were
      identical to those previously found for American stutterers. Although WPS-R
      scores were unrelated to several measures of stuttering severity, analysis of
      extreme scores suggested support for the hypothesis that general anxiety
      moderates stuttering severity. Overall the results are consistent with the
      contention that hypersensitivity to interpersonal stress is manifested in
      stutterers as general anxiety, which is better conceptualized as occurring along
      a continuum than as reflecting generic "overwhelming anxiety" in stutterers.

PMID- 1401230
TI  - The use of artificial neural networks to estimate speech intelligibility from
      acoustic variables: a preliminary analysis.
AB  - Previous research has used regression analysis to attempt to predict the
      intelligibility of hearing-impaired speakers from acoustic speech parameters.
      Improvement of prediction may be achieved by the use of computerized artificial
      neural networks to process mathematically the acoustic input variables as part of
      the intelligibility process. A preliminary scheme for estimating speech
      intelligibility from acoustic parameters using a neural network is outlined and
      preliminary data illustrate its use.

PMID- 1401231
TI  - The effect of gender upon nasalance scores among normal adult speakers.
AB  - Nasometry, pressure-flow, and fundamental frequency data were obtained from 15
      normal female speakers and 15 normal male speakers all of whom were over the age
      of 18 and had Mid-Atlantic dialects. The nasalance scores and nasal cross
      sectional areas of these two groups did not differ. The nasalance scores based on
      three standardized reading passages were not highly correlated with nasal cross
      sectional area or voice fundamental frequency. The clinical significance of these
      findings is discussed.

PMID- 1401232
TI  - Esophageal speaker articulation of /s,z/: a dynamic palatometric assessment.
AB  - Esophageal talker linguapalatal contact patterns and durations during /s/ and /z/
      productions were examined using dynamic palatometry instrumentation. It was found
      that sibilant groove narrowing is a physiologic compensation for a reduced air
      supply in esophageal speech. The place of esophageal /s, z/ articulation was on
      the anterior portion of the alveolar ridge as seen in normal speakers. Average
      medial groove width for esophageal /s/ was narrower than the 5-7-mm groove
      characteristic of normal speakers. Groove widths averaged 3 mm for /s/ and 4 mm
      for /z/. Systematic changes in groove widths across speech sounds, syllable
      position, and vowel context were also observed. Use of a narrower lingual groove
      was interpreted as a significant articulatory maneuver to meter out a limited
      intraoral air supply and effect more normal fricative durations.

PMID- 1401233
TI  - Structuring HIV prevention service delivery systems on the basis of social
      science theory.
AB  - In order to identify the optimal configuration of HIV prevention programs, it is
      necessary to examine different theoretical models of behavior change.
      Cognitive/decision-making theories of human behavior change are compared to
      social learning theories vis-a-vis their influence on the structure of service
      delivery systems. Cognitive/decision-making theories ascribe behavior change to
      the provision of new information and favor the development of homogeneous
      interventions providing clients with information about risk behaviors. These
      interventions are easily standardized across delivery sites and various target
      populations. Social learning theories view behavior change as a series of stages
      and recognize the influence of sociocultural variables. They favor multiple
      heterogeneous interventions in a variety of settings, with the provision of
      skills training as well as information. Ongoing HIV prevention research indicates
      that social learning theories provide a more accurate paradigm of human behavior
      change for the complex behaviors related to HIV risk. Public health agencies must
      therefore continue to strengthen organizational and referral relationships with
      community-based organizations that can provide the specialized prevention
      interventions called for by social learning theory. This will require ongoing
      collaboration and technical assistance.

PMID- 1401234
TI  - Utilization of pediatric health services in Jerusalem.
AB  - The high rate of utilization of health services and rising health care costs in
      Israel, have prompted the need for reform of the health care system. Preventive
      and curative aspects of mother and child health care in Israel have traditionally
      been addressed by independent but parallel health systems. Prior to the pilot
      integration of these services, current patterns of utilization of health services
      by children during their first year of life, and determinants of use, were
      analyzed. Mothers of 651 children from five neighborhoods, representing the
      middle-low, middle and upper social class Jewish population were interviewed.
      Overall, a high degree of compliance with recommended visits to the preventive
      family health centers was found, with an average of eleven visits to the public
      health physician or nurse. The children also made an average of 12 visits to
      curative practitioners. Combined with all other health care consultations, these
      children averaged 26 health care visits in the first year of life. This pattern
      of frequent visitations, and its determinants, is discussed in context of the
      current framework of parallel health care systems. Multivariate analysis revealed
      that the birth order of the child was the key factor in determining the number of
      preventive visits, while the mother's perception of her child's health status
      held the major influence on the number of curative visits. No association between
      utilization of services and social class was discovered. Comparison of
      utilization patterns arising from this study with subsequent investigation of the
      planned integrated services allows for the assessment of the effects of a major
      change in the structure and delivery of pediatric services.

PMID- 1401235
TI  - Predictors of participation in a school-based anti-tobacco activism program.
AB  - This study investigated the predictors of participation in a school-based, anti
      tobacco activism program. Subjects in this study consisted of 7th grade students
      participating in the intervention component of Project S.H.O.U.T., a tobacco use
      prevention program in San Diego County, California. In the activism component, a
      newsletter containing an activism contest was distributed to each student. Small
      prizes were awarded to contest winners at each school. "Activism" included letter
      and petition writing, anti-tobacco poster contests, merchant education, peer
      surveys and magazine subscription cards. A total of 170 students participated in
      the activities, with 81.1 percent participating two or more times. Of those who
      participated, 59 percent were female and 60 percent were White, non-Hispanic. Two
      sets of logistic analyses were conducted. Variables such as SES, gender,
      ethnicity, friends' tobacco use and parental tobacco use were used to predict
      participation in activism activities. The choice of variables was intended to
      provide information regarding activism participation in reference to known
      tobacco risk factors. Results of the first analysis indicated that students with
      a higher SES, and in an urban vs. rural location were more likely to participate
      in the activism activities. The second analysis used the same set of
      characteristics to predict "ever-use" of tobacco. Results of this analysis
      indicated that male gender, low grades, White, non-Hispanic ethnicity, friends'
      and parents' tobacco use were positively associated with tobacco experimentation.

PMID- 1401236
TI  - Health risks associated with residential exposure to extremely low frequency
      electromagnetic radiation.
AB  - Extremely low frequency electromagnetic radiation has received considerable
      attention recently as a possible threat to the health of persons living near high
      tension electric power lines, distribution substations, and even in close
      proximity to common household electric appliances. Results of epidemiological and
      laboratory research are examined to assess risks associated with magnetic fields
      generated by extremely low frequency electromagnetic sources. Health risks
      associated with such fields include a wide variety of ills ranging from
      disruption of normal circadian rhythms to childhood cancers. Risk assessment has
      been particularly difficult to determine in light of an ostensible lack of a dose
      response relationship. Current media sensation fueled in part by an equivocal
      position adopted by the United States Environmental Protection Agency has
      contributed to the controversy. Recommendations for prudent avoidance of possible
      dangers are presented along with policy implications concerning health risks
      associated with magnetic fields.

PMID- 1401238
TI  - Development of astroglial cells in the proliferative matrices, the granule cell
      layer, and the hippocampal fissure of the hamster dentate gyrus.
AB  - The histogenesis of the hamster dentate gyrus was studied with light and electron
      microscopy and antisera against the astrocyte-associated antigens vimentin and
      GFAP, in order to follow the differentiation of radial glial cells and
      astrocytes. The formation of the stratum granulosum is preceded by the
      establishment of successive dentate matrices, which are formed by cells that
      leave the ventricular neuroepithelium and occupy positions above the fimbria
      (suprafimbrial), below the pial surface (subpial), and within the dentate hilus
      (hilar dentate matrix). The subpial dentate matrix invades the marginal zone of
      that region of the cerebral wall, where the stratum granulosum will later
      develop. From the beginning of its existence on embryonal day 13 (E13) up to its
      disappearance about postnatal day 7 (P7), it is characterized by a high content
      of GFAP-positive cells and mitoses. This indicates early gliogenesis in the
      dentate anlage, long before the appearance of the stratum granulosum. Many of the
      bipolar GFAP-positive cells are oriented parallel to the pial surface and have
      focal contacts to the pial basement membrane. The establishment of the subpial
      dentate matrix splits the primordial radial glial scaffold of the
      hippocampal/dentate anlage into two bundles: 1) the suprafimbrial bundle that
      retains its original radial position between ventricle and pial surface; and 2)
      the dorsal glial bundle that traverses the ventral tip of the pyramidal cell
      layer of future CA3. The latter is pushed dorsolaterally, away from the pial
      surface, by the enlargement of the subpial dentate matrix and, later, by the
      suprapyramidal blade. The latter emerges around birth as small radial columns of
      granule cells located between the bent basal parts of the ventralmost fibers of
      the dorsal glial bundle and the subpial dentate matrix. From the beginning of its
      existence it is traversed by unipolar "secondary" radial glial fibers that appear
      to originate from the subpial dentate matrix. Both the supra- and the
      infrapyramidal blades seem to elongate by the addition of postmitotic granule
      cells and "secondary" radial glial cells from the subpial dentate matrix to the
      growing end of the primordial stratum granulosum. The hilar dentate matrix that
      is localized in the prospective hilar region, inside the growing stratum
      granulosum, also contains glial cells that seem to be incorporated into the
      stratum granulosum. The dentate gyrus is demarcated from the CA1 region of the
      hippocampus proper by GFAP-positive cells that populate the hippocampal fissure,
      and that also originate from the subpial dentate matrix.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1401237
TI  - The why, when and whether of condom use among female and male drug users.
AB  - Eight focus groups consisting of all male, all female and mixed male and female
      drug users were conducted to gain an in-depth understanding of beliefs and
      behavior regarding the use of family planning services and contraceptives,
      particularly condom use in an effort to reduce the perinatal transmission of HIV.
      While participants often supported the use of condoms because of STDs and AIDS,
      their unplanned pregnancies and STD histories indicated in-consistent use,
      depending on the partner and the circumstances. The vast majority of both men and
      women did not like to use condoms because it interfered with the spontaneity and
      pleasure of sexual relations, though women seemed more willing to use condoms
      than their partners. Participants varied in their knowledge about the benefits of
      using a condom, in how and when to put it on, in the associations they made
      between condom use and trust and commitment, in the type of partner and
      conditions under which they would use condoms and in their willingness to
      consider condom use as an integral part of their lives. Issues of trust,
      commitment and condom use did not seem to have been resolved in the drug using
      community, particularly among younger people who appeared to have more difficulty
      in negotiating condom use. Promoting the use of condoms needs to be considered as
      part of a larger, multifaceted behavior change effort.

PMID- 1401239
TI  - A crustacean neuronal cytoskeletal protein with characteristics of neurofilaments
      and microtubule-associated proteins.
AB  - The purpose of this study was to characterize further a unique protein that is a
      component of the cytoskeleton of crayfish neurons. This protein, referred to as
      P600, is unique because it is unusually large (Mr greater than 600 kD), and
      because it has characteristics in common with both mammalian microtubule
      associated proteins and neurofilaments. Immunohistochemical techniques have shown
      that P600 colocalizes with microtubules and is a component of the fibrous side
      arms that extend from microtubules (Weaver and Viancour, Brain Res. 544:49,
      1991). We have developed a method for obtaining purified P600 by using gel
      filtration techniques. When viewed by negative staining electron microscopy, P600
      obtained by that method produced 11 nm-wide beaded filaments. The number of
      filaments was strictly related to the P600 concentration in a column fraction. A
      small amount of P600 consistently copurified with taxol-stabilized microtubules.
      The proportion copurifying with microtubules was increased by using apyrase to
      deplete ATP, or by using a nonhydrolyzable ATP analogue to compete with ATP.
      Immunogold labeling localized P600 near the ends of a subset of the fibrous side
      arms extending from endogenous axonal microtubules. Several polyclonal antibodies
      against mammalian microtubule-associated proteins were tested for P600 labeling
      on immunoblots, and positive labeling was obtained with an antiserum directed
      against a region of microtubule-associated protein 1B that has microtubule
      binding activity. Epitope homology between P600, mammalian microtubule-associated
      protein 1B, and the mammalian mid-molecular weight neurofilament subunit is
      discussed in the context of possible evolutionary relationships among these
      cytoskeletal proteins.

PMID- 1401240
TI  - Effects of ethanol on development of dorsal raphe transplants in oculo: a
      morphological and electrophysiological study.
AB  - The purpose of this project was to investigate ethanol influence on the
      development of serotonin-containing (5-HT) neurons of the dorsal raphe nucleus in
      rat. Fetal tissue of embryonic day 17 from the dorsal brainstem was grafted to
      the anterior chamber of the eye of adult albino rats. The experimental group was
      exposed to 16% ethanol in the drinking water, and the control group received
      water ad libitum. After 4 weeks, morphological and electrophysiological
      evaluations were performed. Immunohistochemical analysis showed that 5-HT
      immunoreactive fibers from ethanol-treated transplants had a disturbed outgrowth
      pattern into the host iris as compared to the control group. Furthermore, the
      outgrowth area and axon bundle formation was significantly greater in the control
      group than in the ethanol group. Electrophysiological recordings revealed a dose
      dependent biphasic effect of locally applied ethanol on transplanted
      monoaminergic neurons. Low doses of ethanol (0.5-3 mM) induced an increase in
      basal firing rate of control neurons, while higher doses (10-100 mM) caused
      inhibition. However, monoaminergic neurons in the ethanol group showed a
      decreased neuronal sensitivity to locally applied ethanol. The same dose of
      locally applied ethanol which produced an excitation of neuronal activity in the
      ethanol transplants produced an inhibition in the control grafts. The dose
      response curve was shifted to the right. The present results suggest that chronic
      ethanol exposure during early development leads to altered axonal outgrowth from
      brainstem 5-HT neurons, as well as decreased sensitivity of these neurons to
      locally applied ethanol.

PMID- 1401241
TI  - Destruction of meningeal cells over the medial cerebral hemisphere of newborn
      hamsters prevents the formation of the infrapyramidal blade of the dentate gyrus.
AB  - Meningeal cells participate in the development of the cerebellum both by
      stabilizing the extracellular matrix of the pial surface and by organizing the
      radial glial scaffold and the lamination of the cerebellar cortex. In the present
      study we investigated possible influences of meningeal cells on the development
      of the dentate gyrus, whose ontogenesis has many similarities to that of the
      cerebellum. Meningeal cells were selectively destroyed by injecting newborn
      hamsters with 25 micrograms 6-hydroxydopamine (6-OHDA) into the interhemispheric
      fissure. Twenty-four hours postinjection (p.i.) the meningeal cells over the
      medial cerebral hemispheres were completely destroyed. Thirty days p.i. the
      infrapyramidal blade of the dentate gyrus was almost completely missing, while
      the suprapyramidal blade was hypertrophied, extending with its medial tip almost
      up to the medial surface of the cortex. In order to ascertain that this
      maldevelopment was caused by the destruction of meningeal cells, another group of
      hamsters was pretreated with normetanephrine (NMN) which inhibits the
      extraneuronal uptake of 6-OHDA into meningeal cells. In this group the meningeal
      cells were unaffected by the treatment, and the morphology of the dentate gyrus
      was normal 30 days p.i. of 6-OHDA plus NMN. When the meningeal cells were
      destroyed in later stages of development (postnatal days 1-5), alterations of the
      dentate gyrus could be induced only up to the fourth postnatal day; thereafter, 6
      OHDA treatment left it unchanged. This indicates a critical period of meningeal
      cell influence that coincides with the period of existence of the subpial dentate
      matrix. Analysis of the time course of the defective development revealed that in
      the first 5 days p.i. 1) meningeal cells over the medial cerebral hemisphere were
      destroyed and removed, 2) the pial basement membrane over both the dentate anlage
      and the diencephalon thinned and ruptured, and the adjacent brain parts fused
      focally, 3) many cells of the subpial dentate matrix disappeared from their
      subsurface position, 4) the number of "immature" cells increased in the hilus and
      the subgranular zone of the suprapyramidal blade, 5) the suprapyramidal blade
      elongated and thickened considerably, while the infrapyramidal blade did not
      form. Beyond 5 days p.i. those parts of the pial surface of the dentate anlage
      that had not fused with the diencephalon were repopulated with meningeal cells.
      This reappearance of meningeal cells was accompanied by 1) the restitution of the
      normal morphology of the basement membrane, 2) the reappearance of neuronal and
      glial cells below the pial surface, and 3) the formation of fragments of the
      infrapyramidal blade which later developed a normal appearing
      lamination.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1401242
TI  - Pyramidal neurons of the rat cerebral cortex, immunoreactive to nicotinic
      acetylcholine receptors, project mainly to subcortical targets.
AB  - Cortical neurons immunoreactive to nicotinic acetylcholine receptors (nAChR) of
      the rat brain were characterized with monoclonal antibodies directed to ACh
      binding subunits (alpha 4) or to ACh-structural subunits (beta 2). A
      heterogeneous population of nAChR-LI neurons was found in all cortical regions.
      The most prominent immunoreactive neurons were pyramids of layers V and II-III.
      The nonpyramidal positive neurons were fusiform horizontally oriented neurons of
      layer VIb, small cells of layer I and round or ovoid neurons of layers II-V.
      Double labeled experiments (immunohistochemistry and fluorescent retrograde
      tracers) showed that cholinoceptive pyramidal neurons of layer V project mainly
      to subcortical targets such as caudate-putamen, superior colliculus, and pontine
      nuclei, while very few nAChR positive neurons connect to other cortical areas.
      These findings suggest that the mainly excitatory effect that has been attributed
      to the cholinergic innervation upon the cortical neurons may have a greater
      influence upon the cortico-subcortical output than the corticortical one.

PMID- 1401244
TI  - Morphological variations among output neurons of the olfactory bulb in the frog
      (Rana ridibunda).
AB  - Morphological properties of putative output cells have been studied in detail in
      the olfactory bulb of frogs (Rana ridibunda). Intracellular injection of Lucifer
      Yellow was used to reconstruct individual neurons. Ten different anatomical
      features related to cell shape and position were studied quantitatively. The
      results show that output cells, generally considered to be a homogeneous group in
      the olfactory bulb of amphibians, are, in fact, quite different in their
      morphology. Using multidimensional analysis to examine differences among the
      output neurons, we found that they might be divided into at least two groups. In
      one group, the cell somata were located near the glomerular layer and the
      dendrites lay at large angles with respect to each other. In the other group, the
      cell somata were farther from the glomerular layer and their dendrites lay at
      smaller angles. From their morphology, these two cell groups appear to be
      homologous, respectively, to the superficial/middle tufted cells and deep
      tufted/mitral cells of mammals.

PMID- 1401243
TI  - A unique morphological subtype of horizontal cell in the rabbit retina with
      orientation-sensitive response properties.
AB  - Intracellular recordings were obtained from horizontal cells in the rabbit retina
      to assess the orientation sensitivity of their visual responses to moving and
      stationary rectangular slits of light. Cells were subsequently labeled with
      horseradish peroxidase (HRP) for morphological identification. The responses of A
      type horizontal cells and those of the somatic and axon terminal endings of B
      type horizontal cells (with the exception of one cell) were found to be
      insensitive to the orientation of light stimuli. However, 20 horizontal cells
      encountered within or just superior to the visual streak displayed clear
      orientation-sensitive response properties. These cells were divided into two
      groups: the majority (70%) showed preference for light stimuli oriented parallel
      to the visual streak, whereas the remainder preferred stimuli oriented orthogonal
      to the visual streak. Analysis of the shape of the receptive fields of these
      cells by means of a narrow, displaced slit of light revealed an anisotropy with
      the major or elongated axis of the receptive field of each cell aligned along the
      same angle as its physiological preferred orientation. Morphologically, the
      orientation-sensitive horizontal cells formed a homogeneous group with an
      architecture corresponding to that of elongated A-type or Ae-type horizontal
      cells reported previously in the rabbit retina. These cells showed a marked
      elongation of their dendritic arbors with the major axes oriented either parallel
      or orthogonal to the visual streak. Furthermore, the orientation of the dendritic
      arbor of each cell matched that of its physiological preferred orientation. The
      present results, then, suggest strongly that the orientation sensitivity of Ae
      type horizontal cells results directly from the asymmetry in their dendritic
      arbors. The spatial location and specialized physiology of Ae-type horizontal
      cells suggest that they play a role in the formation of orientation-sensitive
      properties exhibited by more proximal neurons in the rabbit retina.

PMID- 1401245
TI  - Isthmotectal axons make ectopic synapses in monocular regions of the tectum in
      developing Xenopus laevis frogs.
AB  - During the development of binocular maps in the tectum of Xenopus laevis, axons
      that relay input from the ipsilateral eye via the nucleus isthmi undergo a
      prolonged period of shifting connections. This shifting accompanies the dramatic
      change in eye position that takes place as the laterally placed eyes of the
      tadpole move dorsofrontally. There is a concomitant expansion of the proportion
      of tectum that receives contralateral retinotectal input corresponding to the
      binocular portion of the visual field. Electrophysiological recording
      demonstrates that ipsilateral units are present in those rostral tectal zones,
      and anatomical methods show that the isthmotectal axons arborize densely in the
      rostral region but also extend sparser branches into the caudal zone, which is
      occupied by contralateral inputs with receptive fields in the monocular zone of
      the visual field. A mechanism that aligns the ipsilateral and contralateral maps
      is activity-dependent stabilization of isthmotectal axons that exhibit firing
      patterns correlated with those of nearby retinotectal axons. In order for
      activity patterns to function in stabilizing correct connections and promoting
      the withdrawal of incorrect connections, synaptic communication of some sort is
      hypothesized to be essential. We have investigated whether isthmotectal axons
      make morphologically identifiable synapses during development and where such
      synapses are located. We find evidence for morphologically identifiable synapses
      in all regions of the tectum, along with many growth cones and structures that
      are probably immature synapses. As in the adult, the synapses contain round,
      clear vesicles, have asymmetric specializations, and terminate on structures that
      appear to be dendrites. In both adult and tadpole, the rarity of serial synapses
      involving isthmotectal terminals suggests that the interactions between
      retinotectal and isthmotectal inputs are mediated by postsynaptic dendrites.

PMID- 1401246
TI  - Selective vulnerability of the hippocampal pyramidal neurons to hypothyroidism in
      male and female rats.
AB  - Thyroid hormone deficiency has long been considered to affect profoundly such
      cognitive functions as learning and memory, which are known to depend on the
      structural integrity of the hippocampal formation. Since we previously found that
      the number of granule cells of the dentate gyrus is reduced in hypothyroid
      animals, we decided to extend our observations to the pyramidal cells of the
      hippocampus in order to gain further insight into the effects of hypothyroidism
      upon the other neuronal links of the hippocampal trisynaptic circuitry, inasmuch
      as CA1 neurons are known to be particularly vulnerable to aggressive agents.
      Groups of 6 male and 6 female rats aged 30 and 180 days were analysed separately
      after being treated as follows: (1) hypothyroid from day 0 until day 30 (30-day
      old hypothyroid group); (2) respective 30-day-old control; (3) hypothyroid from
      day 0 until day 180 (180-day-old hypothyroid group); (4) hypothyroid until day 30
      and thenceforth maintained euthyroid (recovery group); (5) hypothyroid since day
      30 (adult hypothyroid group); and (6) respective 180-day-old control. The volume
      of the pyramidal cell layer of the CA1 and CA3 regions and the numerical density
      of the respective neurons were evaluated, thereby allowing us to estimate the
      total number of pyramidal cells in each hippocampal region. The areal density and
      the mean nuclear volume of CA1 and CA3 pyramidal cells were also estimated. In
      the CA3 region, we found that hypothyroidism, whatever its duration and time of
      onset, induces a reduction in the volume of the pyramidal cell layer and a
      parallel increase in the numerical density of its neurons, without interfering
      with the total number of pyramidal cells. Conversely, in the CA1 region, thyroid
      hormone deficiency started either neonatally or during maturity was found to lead
      to a decrease in the total number of pyramidal cells. Reductions ranging between
      14.2 and 22.5% were found in 30 and 180-day-old hypothyroid groups. The
      reestablishment of a euthyroid state did not ameliorate the referred neuronal
      loss. The present results support the view that hypothyroidism induces small
      alterations in the structural organization of the hippocampal CA3 region,
      contrary to what happens in CA1 in which neuronal death occurs. Furthermore, the
      data presented herein demonstrate that the total number of CA1 pyramidal cells
      displays sexual dimorphism that is not affected by thyroid hormone
      manipulations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1401247
TI  - GABA-immunoreactive terminals synapse on primate spinothalamic tract cells.
AB  - Gamma-aminobutyric acid (GABA) is a putative inhibitory neurotransmitter in the
      vertebrate nervous system. Several lines of evidence suggest that GABA plays an
      important role in the processing and modulation of sensory input in the spinal
      cord dorsal horn. In the present study, the relationship between GABA
      immunoreactive (GABA-IR) terminals and spinothalamic tract (STT) cells in the
      monkey lumbar cord was investigated. Physiologically characterized STT cells, one
      located in lamina V and two located in lateral lamina IV, were intracellularly
      injected with horseradish peroxidase (HRP). A fourth STT cell, located in lamina
      I, was retrogradely labeled following injection of HRP into the contralateral
      thalamus. Immunogold labeling of ultrathin sections through the cell bodies and
      proximal dendrites of the STT neurons demonstrated that the percentage of the
      GABA-IR terminals in contact with these profiles was 24.7% and 36%, respectively.
      The average STT surface length contacted by GABA-IR terminals for cell bodies and
      proximal dendrites was 18.2% and 26.7%, respectively. For the lamina I cell, 7
      out of 35 (20%) of the terminals were GABA-IR and they covered 9.6% of the
      surface analyzed. These data demonstrate that GABA-IR terminals synapse directly
      on STT cells, constituting a substantial proportion of the terminal population on
      these cells. Furthermore, compared to the cell bodies, a greater percentage of
      the input on the proximal dendrites is GABAergic. These anatomical data are
      consistent with the findings of a previously published iontophoretic study that
      demonstrated that GABA can exert a strong inhibitory influence on STT cells.
      These findings are discussed in relation to GABAergic involvement in tonic and
      phasic inhibition of STT neurons.

PMID- 1401249
TI  - Spatial representation of frequency-modulated signals in the tonotopically
      organized auditory cortex analogue of the chick.
AB  - For auditory communication, many birds, including domestic chicks, use a variety
      of frequency-modulated (FM) sounds. As a first approach to the spatial
      representation of such sounds in the central auditory system, we have analyzed 2
      deoxyglucose (2DG) patterns that were produced by FM stimuli in the tonotopic map
      of the auditory forebrain area (field L/hyperstriatum ventrale complex) of
      domestic chicks. Linear FM signals, varying in the depth and range of modulation,
      and in the direction and rate of the frequency change, were tested. Also included
      were signals designed to mimic species-specific FM calls. All FM stimuli
      activated those regions of the map in which frequencies contained in the stimulus
      spectra were tonotopically represented. However, frequency and amplitude of the
      FM spectra were not faithfully reproduced by activation of the complete
      corresponding tonotopic space. FM signals that differed only in the direction of
      modulation, and therefore had identical long-term spectra, induced maximum 2DG
      activation at different locations of the tonotopic gradient. FM signals that
      differed in the rate of change of frequency produced maxima of 2DG uptake at
      different positions along an isofrequency dimension of the map. These results
      suggest that the direction of modulation may be represented in a complex fashion
      along the tonotopic axis of the structure, whereas the rate of change of
      frequency may be represented along an isofrequency dimension. None of the
      experiments provided evidence of FM-selective regions within the auditory
      forebrain complex. However, numerous telencephalic areas, in addition to the
      primary auditory area, were strongly activated in chicks stimulated with
      artificial "species-specific" FM signals. These areas could be involved in the
      processing of biologically relevant stimuli, requiring attention, recognition,
      and interpretation of the signals.

PMID- 1401248
TI  - Nuclear clefting in dorsal root ganglion neurons: a response to whole body
      vibration.
AB  - Normal adult rabbits were studied in a whole body vibration model which simulates
      the type of environmental exposure associated with vibration-induced low back
      pain. This model has previously been shown to induce changes in pain-related
      neuropeptides in the dorsal root ganglion. Following two weeks of daily exposure
      to whole body vibration, dorsal root ganglia were excised from control and
      vibrated rabbits and prepared for ultrastructural evaluation. Of over 1,200 cells
      sampled, 190 appropriately sectioned cells were analyzed: 32 from immobilized
      controls, 44 from normal controls, and 114 from vibrated animals. Analysis of
      nuclear contours revealed more prevalent and more extensive clefting of the
      nuclear membrane in vibrated cells. The membrane lining these clefts was
      traversed by numerous pores; density of these pores was 46% greater than in
      adjacent nonclefted segments (p less than .001). Number of clefts per nucleus was
      increased by 39% in vibrated animals. Cleft area represented 1.19% of nuclear
      area in vibrated cells compared to 0.74% in controls (p less than .001). Numerous
      mitochondria and free ribosomes and abundant rough endoplasmic reticulum were
      located within the cleft spaces of vibrated cells. Pores in the cleft membrane
      appeared normal, supporting the conclusion that the clefts are structural
      alterations rather than fixation or sectioning artifacts. Changes in dorsal root
      ganglion neuropeptides seen in previous studies of vibrated animals may result
      from increased or redirected cellular synthesis. Ultrastructural changes seen in
      these vibrated dorsal root ganglion neurons are consistent with such an
      alteration in metabolism and could reflect increased synthesis of pain-related
      neuropeptides.

PMID- 1401250
TI  - 5'-nucleotidase: a new marker for striosomal organization in the rat
      caudoputamen.
AB  - The distribution of the adenosine-producing ectoenzyme 5'-nucleotidase was
      studied by means of a histochemical lead technique in the caudoputamen of normal
      adult rats and of rats in which injections either of 6-hydroxydopamine in the
      medial forebrain bundle or of ibotenic acid in the caudoputamen had been made 1-3
      weeks previously. The patterns of striatal 5'-nucleotidase activity in these
      animals were compared in serial sections to the patterns of calbindin-D28k
      immunoreactivity and of 3H-naloxone ligand binding, which respectively mark the
      known matrix and striosome (patch) compartments of the caudoputamen. In the
      normal rats, 5'-nucleotidase activity was differentially concentrated in
      striosomes, where it produced a dense staining of the neuropil. The enzymatic
      staining followed a striosomal distribution in all but the caudal caudoputamen.
      Within the striatal matrix, 5'-nucleotidase staining also observed a lateromedial
      density gradient. Depletion of the dopamine-containing nigrostriatal innervation
      of the caudoputamen with 6-hydroxydopamine did not alter the striosomal
      selectivity of 5'-nucleotidase activity. Destruction of intrastriatal neurons by
      ibotenic acid led to a strongly 5'-nucleotidase-positive gliosis within the
      resulting necrotic region. Elsewhere in the caudoputamen, the enzyme's striosomal
      distribution was not detectably altered. We conclude that 5'-nucleotidase
      histochemistry provides an advantageous tool for detecting the striosomal
      architecture of the rat's caudoputamen. Moreover, 5'-nucleotidase is prominently
      associated with glial membranes in the central nervous system, so that the
      concentration of this enzyme in striosomes could mark these as sites of selective
      glial populations within striatum. These properties and actions of 5'
      nucleotidase in purinergic neurotransmission and in neuroadhesion may contribute
      to the specialized functions of striosomes and matrix.

PMID- 1401251
TI  - Genesis of neurons in the retinal ganglion cell layer of the monkey.
AB  - We have analyzed the genesis of various neuronal classes and subclasses in the
      ganglion cell layer of the primate retina. Neurons were classified according to
      their size and the time of their origin was determined by pulse labeling with 3H
      thymidine administered to female monkeys 38 to 70 days pregnant. All offspring
      were sacrificed postnatally, and their retinas processed for autoradiography. The
      somata of cells in the retinal ganglion cell layer generated on embryonic day (E)
      38 ranged from 9 to 14 microns in diameter. Between E40 and E56, the minimum soma
      diameter remained around 8-9 microns, while the maximum gradually increased to 22
      microns. As a consequence, the means of the distributions of labeled cells also
      increased with age, from 11.8 microns diameter for cells generated on E38 to 14.6
      microns diameter at E56. Over this period the percentage of labeled cells in the
      10.5-16.5 microns and greater than 16.5 microns diameter range gradually
      increased. The proportion of the labeled cells in the less than 10.5 microns
      diameter range decreased from E38 to E45, but subsequently increased rapidly. At
      the end of neurogenesis in the retinal ganglion cell layer, around E70, most
      labeled cells were considerably smaller (7-9 microns) than those generated
      earlier. Our results indicate that within the ganglion cell layer of the macaque,
      neurons of small caliber are generated first, followed successively by medium
      sized cells. Large, putative P alpha cells are generated late. The production
      between E56 and E70 of cells with the smallest somata suggests that the last
      generated neurons in the ganglion cell layer are predominantly displaced amacrine
      cells. Within the same sector of retina, different classes of neurons in the
      ganglion cell layer of the rhesus monkey appear to have a sequential schedule of
      production.

PMID- 1401252
TI  - Vasopressin innervation of sexually dimorphic structures of the gerbil forebrain
      under various hormonal conditions.
AB  - The distribution of vasopressin-immunoreactive fibers in the forebrain of male
      and female gerbils was studied, focusing on the lateral septum and the sexually
      dimorphic area (SDA) found at the border between the medial preoptic area and the
      anterior hypothalamus. To study hormonal influences on the densities of these
      fibers, some animals of each sex were gonadectomized or gonadectomized and given
      testosterone. Others were given sham operations. High densities of vasopressin
      immunoreactive fibers were found in the lateral septum. In the SDA, the densities
      of these fibers varied considerably. Many were found in the medial half of the
      medial SDA, but few in the lateral SDA. Vasopressin-immunoreactive fibers were
      also sparse in the lateral half of the medial SDA, except for a dense cluster in
      the SDA pars compacta of males. Similar but smaller clusters were seen in the
      same location in females although the SDA pars compacta could not be detected in
      Nissl-stained sections from the female brains. Fiber densities in two areas, the
      lateral septum and the lateral SDA, were sensitive to gonadal steroids. In both
      cases, castration reduced fiber density and testosterone enhanced it. In
      addition, fiber densities in two areas, the lateral septum and the medial SDA,
      were sexually dimorphic. In each case, fiber density was greater in males. There
      was no hormonal effect, however, on the fiber densities in the medial SDA. The
      fact that the fiber plexuses in the lateral septum and the medial SDA respond
      differently to gonadal steroids suggests that they arise from different cells and
      possibly from different areas of the brain. The vasopressin-immunoreactive fibers
      in the lateral septum probably come from steroid-sensitive vasopressin neurons in
      the bed nucleus of the stria terminalis. Those in the medial SDA may originate in
      the dorsal aspect of the suprachiasmatic nucleus where vasopressin-immunoreactive
      cell bodies were seen.

PMID- 1401253
TI  - Dendritic morphology of pyramidal neurones of the visual cortex of the rat. IV:
      Electrical geometry.
AB  - Features of the dendritic morphology of pyramidal neurones of the visual cortex
      of the rat that are relevant to the development of models of their passive
      electrical geometry were investigated. The sample of 39 neurones that was used
      came from layers 2/3 and 5. They had been recorded from and injected
      intracellularly with horseradish peroxidase (HRP) in vitro as part of a previous
      study (Larkman and Mason, J. Neurosci 10:1407, 1990). These cells had been
      reconstructed and measured previously by light microscopy. The relationship
      between the diameters of parent and daughter dendrites during branching was
      examined. It was found that most dendrites did not closely obey the "3/2 branch
      power relationship" required for representation of the dendrites as single
      equivalent cylinders. Estimates of total neuronal membrane area ranged from
      27,100 +/- 7,900 microns2 for layer 2/3 cells to 52,200 +/- 11,800 microns2 for
      thick layer 5 cells. Dendritic spines contributed approximately half the total
      membrane area. Both neuronal input resistance and the ratio of membrane time
      constant to input resistance were correlated with neuronal membrane area as
      measured anatomically. The relative electrical lengths of the different dendrites
      of individual neurones were investigated, by using simple transformations to take
      account of the differences in diameter and spine density between dendritic
      segments. A novel "morphotonic" transformation is described that represents the
      purely morphological component of electrotonic length. Morphotonic lengths can be
      converted into electrotonic lengths by division by a "morphoelectric factor"
      ([Rm/Ri]1/2). This procedure has the advantage of separating the steps involving
      anatomical and electrical parameters. These transformations indicated that the
      dendrites of the apical terminal arbor were much longer electrically than the
      basal or apical oblique dendrites. In relative electrical terms, most apical
      oblique trees arose extremely close to the soma, and terminated at similar
      distances to the basals. These results indicate that the dendrites of these
      pyramidal cells cannot be represented as single equivalent cylinders. The
      electrotonic lengths of the dendrites were calculated by using the electrical
      parameters specific membrane capacitance (Cm), intracellular resistivity (Ri),
      and specific membrane resistivity (Rm). Conventional values were assumed for Cm
      (1.0 muFcm-2) and Ri (100 omega cm), but three different Rm values were used for
      each cell. Two of these were within the conventionally accepted range (10,000
      20,000 omega cm2), while the third value was an order of magnitude higher, in
      line with some recent evidence from modeling and whole-cell recording
      studies.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1401254
TI  - Position of growth cones within the retinal nerve fibre layer of fetal ferrets.
AB  - Optic axons are added to the retinal nerve fibre layer of fish along its vitreal
      border in a chronotopic manner. Likewise, the optic tract of all vertebrate
      species acquires axons preferentially along the superficial surface of the
      pathway. We have examined the developing retina of fetal ferrets (Mustela
      putorius furo) aged between embryonic day 27 (E27) and E34 to see whether a
      similar segregation of growth cones is apparent within the mammalian retinal
      nerve fibre layer. The distributions of growth cone, "wrist" (thick trailing
      portion of the growth cone), axonal, and glial profiles were determined from
      electron micrographs, and expressed as a percentage of neural profiles for
      several retinal locations. The retinal nerve fibre layer of fetal ferrets
      contains radially elongated bundles of fibres composed of axonal, wrist, and
      growth cone profiles. Glial processes of varying density divide the adjacent
      bundles, occasionally subdividing them in the plane of the retina, and give rise
      to endfeet lining the basal lamina and separating the optic axons from the
      latter. Growth cones within the developing fibre layer represented about 2.4% of
      profiles at E28, while at later developmental stages (E34), this value fell to
      about 0.6%. During this period of axonal outgrowth, growth cones were not
      preferentially segregated toward the vitreal basal lamina or the glial endfeet
      within the nerve fibre layer. Rather, they were found scattered throughout the
      axon bundles of the fibre layer. While there were differences in the proportion
      of immature profiles found within the vitreal half compared to the scleral half
      of the fibre layer, such that more growth cones and wrists were found vitreally,
      there was no clear accumulation of them in association with features of the
      vitreal margin. The present results show that young and old optic axons course
      together throughout the depth of the nerve fibre layer. A chronotopic mode of
      pathway genesis such as seen in the optic fibre layer of fish or in the optic
      tract of mammals is not present in the nerve fibre layer of ferrets. Differences
      in growth cone behaviour in the optic fibre layer and tract indicate that the
      mechanisms governing pathway formation differ along its course.

PMID- 1401255
TI  - The organization of the thalamocortical connections of the mediodorsal thalamic
      nucleus in the rat, related to the ventral forebrain-prefrontal cortex
      topography.
AB  - The medial and central segments of the mediodorsal nucleus of the thalamus (MD)
      receive afferents from the ventral forebrain, including the piriform cortex, the
      ventral pallidum, and the amygdaloid complex. Because MD is reciprocally
      interconnected with prefrontal and agranular insular cortical areas, it provides
      a relay of ventral forebrain activity to these cortical areas. However, there are
      also direct projections from the piriform cortex and the amygdala to the
      prefrontal and agranular insular cortices. This study addresses whether this
      system has a "triangular" organization, such that structures in the ventral
      forebrain project to interconnected areas in MD and the prefrontal/insular
      cortex. The thalamocortical projections of MD have been studied in experiments
      with injections of retrograde tracers into prefrontal or agranular insular
      cortical areas. In many of the same experiments, projections from the ventral
      forebrain to MD and to the prefrontal/insular cortex have been demonstrated with
      anterograde axonal tracers. The connections of the piriform cortex (PC) with MD
      and the prefrontal/insular cortex form an organized triangular system. The PC
      projections to the central and medial segments of MD and to the lateral orbital
      cortex (LO) and the ventral and posterior agranular insular cortices (AIv and
      AIp) are topographically organized, such that more caudal parts of PC tend to
      project more medially in MD and more caudally within the orbital/insular cortex.
      The central and medial portions of MD also send matching, topographically
      organized projections to LO, AIv and AIp, with more medial parts of MD projecting
      further caudally. The anterior cortical nucleus of the amygdala (COa) also
      projects to the dorsal part of the medial segment of MD and to its cortical
      targets, the medial orbital area (MO) and AIp. The projections of the
      basal/accessory basal amygdaloid nuclei to MD and to prefrontal cortex, and from
      MD to amygdaloceptive parts of prefrontal cortex, are not as tightly organized.
      Amygdalothalamic afferents in MD are concentrated in the dorsal half of the
      medial segment. Cells in this part of the nucleus project to the amygdaloceptive
      prelimbic area (PL) and AIp. However, other amygdaloceptive prefrontal areas are
      connected to parts of MD that do not receive fibers from the amygdala. Ventral
      pallidal afferents are distributed to all parts of the central and medial
      segments of MD, overlapping with the fibers from the amygdala and piriform
      cortex. Fibers from other parts of the pallidum, or related areas such as the
      substantia nigra, pars reticulata, terminate in the lateral and ventral parts of
      MD, where they overlap with inputs from the superior colliculus and other
      brainstem structures.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1401256
TI  - Time course of dorsal root axon regeneration into transplants of fetal spinal
      cord: I. A light microscopic study.
AB  - Cut dorsal root axons regenerate into intraspinal transplants of fetal spinal
      cord and establish synaptic connections there. The aims of the present study were
      to describe the progression of dorsal root growth within the transplants and the
      maturation of transplant morphology and to determine whether the regenerated
      dorsal root axons persist within the transplants or eventually withdraw.
      Embryonic (E) day 14 spinal cord was grafted into the lumbar enlargement of adult
      Sprague-Dawley rats, and the L4 or L5 dorsal root was cut and juxtaposed to the
      transplants. The morphology of the transplants was examined from 1 day to over 1
      year after surgery, and the regenerated dorsal roots were labeled with
      immunohistochemical methods to study the subset that contains calcitonin gene
      related peptide (CGRP). Embryonic spinal cord transplants survived and grew
      within the host spinal cord in over 90% of the animals. Transplant volume
      increased and the morphology of the transplants matured over the first 12 weeks
      and then did not change for 48-60 weeks. During the first week the transplants
      were composed of dissociated neurons, glia, and hematogenous cells with
      considerable extracellular space between them. Subsequently, the grafted neurons
      became densely aggregated, and non-neuronal elements such as inflammatory cells
      and myelin debris disappeared. CGRP-immunoreactive dorsal roots began to
      regenerate into the transplants within 24 hours, formed dense bundles by 4 days,
      and were still present at 60 weeks, the longest survival period examined.
      Myelination of axons within transplants began at 2 weeks. Quantitative analysis
      showed that the area of the transplants occupied by CGRP-labeled axons and the
      distribution area of the labeled axons within the transplants increased until 12
      weeks and persisted unchanged for over 48 weeks. These results indicate that
      regenerated dorsal root axons are permanently maintained within transplants of
      embryonic spinal cord and suggest that the transplants can contribute to the
      permanent restoration of damaged intraspinal neural circuits.

PMID- 1401257
TI  - Effects of advancing age on peripheral nerve regeneration.
AB  - Following axotomy, the regrowth of peripheral axons takes longer in older
      individuals than in young ones. The present study compares the crush-induced
      process of degeneration and regeneration in the buccal branch of the facial motor
      nerve in groups of rats aged 3 months and 15 months. Observations are based on
      qualitative and quantitative analyses of the nerve 20 mm from the site of injury
      in rats 1, 2, 4, 16, 21, 28, and 56 days after crush. The buccal branch is purely
      motor and contains a unimodal population of about 1,600 axons commonly in a
      single fascicle. During the first 28 days post crush (dpc) in the 3-month
      animals, the progression of myelin and axon degeneration, myelin clearance,
      regrowth of axon sprouts, and axon maturation are relatively synchronized and
      uniform. In the older rats, the degeneration of myelin and axons, myelin
      clearance, and the appearance of axon sprouts at the site of sample are all
      delayed. In the younger animals, axon sprouts increase in numbers from their
      first appearance at 4 dpc through the 2 weeks examined following the restoration
      of whisking behavior. The numbers of regenerating older axons increase at a rate
      comparable to that in the younger animals through the time that bilaterally
      symmetrical whisking behavior is evident, but afterwards the number of axon
      sprouts decreases. At 2 months after crush the young animals have 30% more fibers
      in the buccal branch than control nerves, while the older animals have fewer than
      control numbers. In the 3-month regenerated nerve, 2 months post crush, 30% of
      the regenerated fibers are of very small caliber, less than 3 microns2 in cross
      sectional area, and typically these small axons have unusually thick myelin
      sheaths; the older nerves do not have such a skewed distribution of axon areas.
      The older regenerated axons at 2 months post crush have an unusually high density
      of microtubules compared to the younger regenerated ones (and controls), and the
      ratio of neurofilaments to microtubules is very low. The conclusions are that
      motor neurons in older animals regenerate damaged axons after a delay not
      apparent in the young; the strong regenerative response apparent initially in
      animals of both age groups is not maintained in the older animals; and the
      relationship between the numerical density of cytoskeletal elements and the axon
      cross-sectional area deviates from normal in the regenerated axons of the older
      animals.

PMID- 1401258
TI  - Expression of s-laminin and laminin in the developing rat central nervous system.
AB  - The extracellular matrix component, s-laminin, is a homologue of the B1 subunit
      of laminin. S-laminin is concentrated in the synaptic cleft at the neuromuscular
      junction and contains a site that is adhesive for motor neurons, suggesting that
      it may influence neuromuscular development. To ascertain whether s-laminin may
      also play roles in the genesis of the central nervous system, we have examined
      its expression in the brain and spinal cord of embryonic and postnatal rats. S
      laminin was not detectable in synapse-rich areas of adults. However, s-laminin
      was present in discrete subsets of three laminin-containing structures: (1) In
      the developing cerebral cortex, laminin and s-laminin were expressed in the
      subplate, a transient layer through which neuroblasts migrate and cortical
      afferents grow. Both laminin and s-laminin disappeared as embryogenesis
      proceeded; however, laminin was more widely distributed and present longer than s
      laminin. (2) In the developing spinal cord, laminin was present throughout the
      pia. In contrast, s-laminin was concentrated in the pia that overlies the floor
      plate, a region in which extracellular cues have been postulated to guide growing
      axons. (3) In central capillaries, s-laminin appeared perinatally, an interval
      during which the blood-brain barrier matures. In contrast, laminin was present in
      capillary walls of both embryos and adults. To extend our immunohistochemical
      results, we used biochemical methods to characterize s-laminin in brain. We found
      that authentic s-laminin mRNA is present in the embryonic brain, but that brain
      derived s-laminin differs (perhaps by a posttranslational modification) from that
      derived from nonneural tissues. We also used tissue culture methods to show that
      glia are capable of synthesizing "brain-like" s-laminin, and of assembling it
      into an extracellular matrix. Thus, glia may be one cellular source of s-laminin
      in brain. Together, these results demonstrate that s-laminin is present in the
      developing central nervous system, and raise the possibility that this molecule
      may influence developmental processes.

PMID- 1401259
TI  - Cholinergic innervation of the human striatum, globus pallidus, subthalamic
      nucleus, substantia nigra, and red nucleus.
AB  - The anatomical organization of cholinergic markers such as acetylcholinesterase,
      choline acetyltransferase, and nerve growth factor receptors was investigated in
      the basal ganglia of the human brain. The distribution of choline
      acetyltransferase-immunoreactive axons and varicosities and their relationship to
      regional perikarya showed that the caudate, putamen, nucleus accumbens, olfactory
      tubercle, globus pallidus, substantia nigra, red nucleus, and subthalamic nucleus
      of the human brain receive widespread cholinergic innervation. Components of the
      striatum (i.e., the putamen, caudate, olfactory tubercle, and nucleus accumbens)
      displayed the highest density of cholinergic varicosities. The next highest
      density of cholinergic innervation was detected in the red nucleus and
      subthalamic nucleus. The level of cholinergic innervation was of intermediate
      density in the globus pallidus and the ventral tegmental area and low in the pars
      compacta of the substantia nigra. Immunoreactivity for nerve growth factor
      receptors (NGFr) was confined to the cholinergic neurons of the basal forebrain
      and their processes. Axonal immunoreactivity for NGFr was therefore used as a
      marker for cholinergic projections originating from the basal forebrain (Woolf et
      al., '89: Neuroscience 30:143-152). Although the vast majority of striatal
      cholinergic innervation was NGFr-negative and, therefore, intrinsic, the striatum
      also contained NGFr-positive axons, indicating the existence of an additional
      cholinergic input from the basal forebrain. This basal forebrain cholinergic
      innervation was more pronounced in the putamen than in the caudate. The
      distribution of NGFr-positive axons suggested that the basal forebrain may also
      project to the globus pallidus but probably not to the subthalamic nucleus,
      substantia nigra, or red nucleus. The great majority of cholinergic innervation
      to these latter three structures and to parts of the globus pallidus appeared to
      come from cholinergic neurons outside the basal forebrain, most of which are
      probably located in the upper brainstem. These observations indicate that
      cholinergic neurotransmission originating from multiple sources is likely to play
      an important role in the diverse motor and behavioral affiliations that have been
      attributed to the human basal ganglia.

PMID- 1401260
TI  - Spatial density and immunoreactivity of bipolar cells in the macaque monkey
      retina.
AB  - The anatomical substrates of spatial and color vision in the primate retina are
      investigated by measuring the immunoreactivity and spatial density of bipolar,
      amacrine and horizontal cells in the inner nuclear layer of the macaque monkey
      retina. Bipolar cells can be distinguished from amacrine and horizontal cells by
      their differential immunoreactivity to antisera against glutamate, glycine, GABA,
      parvalbumin, calbindin (CaBP D-28K), and the L7 protein from mouse cerebellum.
      The spatial density of bipolar cells is compared to the densities of
      photoreceptors and ganglion cells at different retinal eccentricities. In the
      centralmost 2 mm, cone bipolar cells outnumber ganglion cells by about 1.4:1. The
      density of cone bipolar cells is thus high enough to allow for input to different
      (parasol and midget) ganglion cell classes by different (diffuse and midget)
      bipolar cell classes. The density gradient of cone bipolar cells follows closely
      that of ganglion cells in central retina but falls less steeply in peripheral
      retina. This suggests that the convergence of cone signals to the receptive
      fields of ganglion cells in the peripheral retina occurs in the inner plexiform
      layer. The density of cone bipolar cells is 2.5-4 times that of cones at all
      eccentricities studied, implying that cone connectivity to bipolar cells remains
      constant throughout the retina. Different subgroups of bipolar cells are
      distinguished by their relative immunoreactivity to the different antisera. All
      rod and cone bipolar cells show moderate to strong glutamate-like
      immunoreactivity. The bipolar cells that show weak to moderate GABA-like
      immunoreactivity are also labeled with the antiserum to the L7 protein and are
      thus identified as rod bipolar cells. Nearly half of all cone bipolar cells
      showed glycine-like immunoreactivity. The results suggest that the inhibitory
      neurotransmitter candidates GABA and glycine are segregated respectively in rod
      and cone bipolar cell pathways. A diffuse, cone bipolar cell type can be
      identified by the anti-parvalbumin and the anti-calbindin antisera. All
      horizontal cells show parvalbumin-like immunoreactivity. Nearly all amacrine
      cells show GABA-like or glycine-like immunoreactivity; a variety of
      subpopulations also show immunoreactivity to one or more of the other markers
      used.

PMID- 1401262
TI  - Morphology of intracellularly labeled interneurons in the dentate gyrus of the
      immature rat.
AB  - Although many aspects of the morphological development of interneurons in the
      dentate gyrus have been described, the full extent of their dendrites and local
      axon projections in immature rodents has not been examined. Here intracellular
      labeling was used to assess the branching patterns of interneurons in the dentate
      gyrus of rat pups between 7 and 9 days of age. Labeled neurons were located
      within or just below the granule cell layer, and most were classified as
      GABAergic basket neurons on the basis of their dendritic morphologies. All
      labeled interneurons exhibited immature characteristics. Spines were present on
      cell bodies and dendrites, and growth cones were visible on some dendrites and
      axons. In spite of these immature features, the dendrites and axon arbors of the
      labeled neurons were extensive. Many apical dendrites reached the top of the
      molecular layer, and a number of basal dendrites extended to the CA3 pyramidal
      cell layer of the hippocampus. Elaborate axon plexuses were present within the
      dentate gyrus itself, and axon collaterals of several neurons extended beyond the
      dentate gyrus to branch within regions CA3 and CA1 of the hippocampus. These
      results indicate that the dendrites and axon collaterals of dentate interneurons
      are extensive at a time when the principal neurons, the granule cells, are still
      proliferating. These data are consistent with the idea that GABAergic
      interneurons may influence granule cell development in the dentate gyrus, as well
      as pyramidal cell maturation in the hippocampus proper.

PMID- 1401261
TI  - Quantitative analysis of bulbospinal projections from the rostral ventrolateral
      medulla: contribution of C1-adrenergic and nonadrenergic neurons.
AB  - The contribution of C1-adrenergic and nonadrenergic neurons to the spinal
      projection from the rostral ventrolateral medulla (RVLM) and their relative
      innervation density throughout thoracic spinal segments were examined by
      combining the Fluorogold (FG) retrograde tracing technique with immunofluorescent
      labeling for the epinephrine-synthesis enzyme phenylethanolamine N
      methyltransferase (PNMT). The results indicate that the RVLM-spinal projection is
      comprised of both PNMT-positive and PNMT-negative neurons located in the
      subretrofacial area of the RVLM, approximately 1 to 1.7 mm rostral to obex. The
      bulbospinal projection from the RVLM is predominantly ipsilateral, and
      bulbospinal neurons do not appear to be organized within the RVLM in a manner
      indicating their segmental termination site. Eighty-one percent (+/- 4%, n = 2)
      of the PNMT-positive cells in the ipsilateral subretrofacial RVLM were
      retrogradely labeled after unilateral FG injections into multiple thoracic levels
      of the intermediolateral cell column (IML). Following single level FG injections,
      the number of retrogradely labeled PNMT-positive neurons in the subretrofacial
      RVLM decreased with injections in more caudal thoracic segments, indicating a
      heavier innervation of the upper thoracic IML by C1 neurons. PNMT-negative
      neurons were the main component of the RVLM-spinal population with 63 +/- 8% (n =
      7) of the non-PNMT-containing neurons within the ipsilateral subretrofacial RVLM
      innervating all thoracic levels of the IML. The results indicate that both C1
      adrenergic and nonadrenergic neurons in the RVLM make a substantial contribution
      to the innervation of the IML.

PMID- 1401263
TI  - The human transient subpial granular layer: an optical, immunohistochemical, and
      ultrastructural analysis.
AB  - The cytological features, origin, migration, and fate of the subpial granular
      layer cells of the human embryonic cerebral cortex are studied with light and
      electron microscopy, Golgi impregnations, and immunocytochemical staining with
      the microtubule associated protein 2 and glial fibrillary acidic protein
      antibodies. Subpial granular layer (SGL) cells form a distinct neuronal
      population in the molecular layer, characterized by a small dark nucleus with
      abundant chromatin clumps and prominent nucleoli, and a lightly stained cytoplasm
      containing few organelles. Somata and processes of SGL cells are intensively
      stained with microtubule-associated protein 2 antibody but do not express glial
      fibrillary acidic protein antibody. These cells apparently originate from the
      olfactory germinative zone. They follow two major strands from the olfactory
      subventricular zone to the subpial region. Subsequently, they migrate
      tangentially at the subpial level to all cortical regions, as is observed on
      Golgi and ultrastructural preparations. They constitute a transient population
      that penetrates the deep molecular layer and subsequently disappear from it.
      Several cytological features of these cells suggest an inward migration with
      growth of a radial process toward the cortical plate and subsequent nuclear
      translocation. The fate and the role of this new phylogenetic neuronal population
      has yet to be determined although the abundance of degenerating SGL cells in the
      deep molecular layer suggests at least partial degeneration.

PMID- 1401264
TI  - Time of ganglion cell genesis in relation to the chiasmatic pathway choice of
      retinofugal axons.
AB  - The time of generation of retinal ganglion cells in fetal cats has been related
      to the course taken later by their axons in the optic chiasm. The ganglion cells
      were labelled with tritiated thymidine either on embryonic day (E) 26 or on E-30.
      When the cats were mature, ganglion cells were retrogradely labelled with
      horseradish peroxidase injected into one optic tract. The distribution of double
      labelled cells showed that cells in the temporal retina generated on E-26 all
      have axons that take an uncrossed course in the chiasm, whereas, of the cells
      generated on E-30 in the temporal retina, some take a crossed course and others
      take an uncrossed course. The uncrossed axons of the E-26 cohort come from cells
      having a central distribution on the retina. For the E-30 cohort, the uncrossed
      axons come from cells having a relatively peripheral distribution, whereas the
      crossed axons come from more central cells. The present results suggest that the
      mechanism which serves to direct temporal retinal axons into the ipsilateral
      optic tract weakens as development proceeds. In principle, the change may occur
      in either a chiasmatic signal, read by temporal but not nasal optic axons, or in
      a retinal label, carried by temporal but not nasal cells and their processes.
      Since temporal retinal cells born concurrently at different places can project to
      opposite optic tracts, a retinal signal that deteriorates with time in a
      centroperipheral fashion is favored by the present results.

PMID- 1401265
TI  - Fine structure and blood-brain barrier properties of the central nervous system
      of a dipteran larva.
AB  - Using scanning and transmission electron microscopy, we studied basic
      ultrastructure, membrane specializations, and blood-brain barrier properties of
      the ventral ganglion and abdominal nerves of the last (third) instar larva of a
      dipteran fly, Delia platura. Both ganglion and nerves are covered with a non
      cellular neural lamella. A monolayer of flattened perineurial cells lies beneath
      the neural lamella. Perineurial cells contain stores of metabolites and nutrients
      and these cells extensively interdigitate with one another. An extensive
      extracellular series of channels pervades perineurial cells. Glial cells beneath
      the perineurium envelope but do not entwine axons. In a minority of cases,
      adjacent axons in nerve and neuropil appear to be contiguous without glial
      intervention. Extensive (pleated) septate junctions with triangular septa are
      present between perineurial cells. Hemidesmosomes, half desmosomes (a first
      report for invertebrates), and desmosomes were also observed. Although no tight
      junctions were discovered, an effective blood-brain barrier exists, and tracer
      (ionic lanthanum) in no case reached neuronal surfaces. Extracellular tracer
      halted within the extensive septate junctions between perineurial cells. We
      postulate that in the absence of tight junctions the functional blood-brain
      barrier is effected by the septate junctions in the central nervous system of the
      Delia larva.

PMID- 1401266
TI  - Contractile proteins in the hyaline cells of the chicken cochlea.
AB  - Hyaline cells are a single layer of epithelial cells found at the inferior edge
      of the sensory epithelium in the chick cochlea. They rest directly above a
      specialized region of the basilar membrane at a point where it connects to the
      fibrocartilaginous skeleton of the cochlear duct. The basal cytoplasm of the
      hyaline cells contains a bundle of linearly aligned actin filaments that resemble
      stress fibers in their organization. The actin filaments are anchored in the
      basal plasma membranes of the cells, which are, in turn, associated with the
      underlying basal lamina and the extracellular matrix of the basilar membrane. We
      have used a combination of transmission electron microscopy, differential
      interference-contrast and epifluorescence light microscopy, and confocal laser
      scanning microscopy to study the composition and organization of these actin
      bundles within the hyaline cells. The bundles are arranged into triangular wedges
      that are oriented radially across the basilar membrane. Each cell contains one or
      two actin wedges. Adjacent cells can have them aligned in opposite directions so
      that in a whole-mount surface preparation they appear as interdigitations.
      Immunofluorescent staining of the hyaline cells has shown that smooth muscle
      myosin and alpha-actinin are co-localized to the actin bundles. Smooth muscle
      myosin is also found throughout the cytoplasm of the cells. The fact that hyaline
      cells in the chick cochlea are contacted by efferent nerve fibers suggests that
      these cells may regulate tension on the basilar membrane via the specialized
      bundle of actin filaments.

PMID- 1401267
TI  - Projections from the commissural subnucleus of the nucleus of the solitary tract:
      an anterograde tracing study in the cat.
AB  - The commissural subnucleus (COM) of the nucleus of the solitary tract (NTS) is
      known to receive primary afferents from the lungs and other viscera innervated by
      the vagus nerve, and thus to participate in central autonomic and respiratory
      control. The aim of the present study was to identify the areas of terminal
      arborizations of COM neurons in order to examine brainstem sites which may be
      involved in reflex responses mediated by these neurons. The projections were
      studied in cats, using biocytin as an anterograde tracer. Labeled fibers and
      terminal boutons were visualized by horseradish-peroxidase histochemistry, 2-3
      days after microinjection of the tracers into the COM 1-2 mm caudal to the obex.
      Labeled axons were examined in the brainstem from the rostral pons to the caudal
      medulla and were found bilaterally, with an ipsilateral predominance, mainly in
      the following regions: (1) The dorsolateral rostral pons. Terminal boutons were
      observed in the lateral and medial parabrachial nuclei, Kolliker-Fuse nucleus,
      and around the mesencephalic trigeminal tract. This area corresponds to the
      pontine respiratory group also known as the "pneumotaxic center." (2) The pontine
      area dorsolateral to the superior olivary nucleus. This region contains the A5
      noradrenergic cell group; (3) Near the ventral surface, below the facial nucleus.
      This area overlaps with the 'retrotrapezoid nucleus.' (4) Respiration-related
      areas of the medulla, including the dorsal and ventral respiratory groups, and
      the Botzinger complex. (5) The dorsal motor nucleus of the vagus. These results
      suggest that the COM is involved in reflex arcs, which have both respiratory
      functions and autonomic functions. The pathway to the dorsolateral pons, which
      has been identified in our recent electrophysiological study is likely to play a
      role in mediating respiratory responses from pulmonary rapidly adapting
      receptors. Other pathways may represent additional projections from second-order
      neurons receiving input from this group of lung receptors, or projections from as
      yet unidentified neurons that relay information from different afferents
      terminating in the COM.

PMID- 1401268
TI  - Corticotectal projections in the cat: anterograde transport studies of twenty
      five cortical areas.
AB  - Retrograde transport studies have shown that widespread areas of the cerebral
      cortex project upon the superior colliculus. In order to explore the organization
      of these extensive projections, the anterograde autoradiographic method has been
      used to reveal the distribution and pattern of corticotectal projections arising
      from 25 cortical areas. In the majority of experiments, electrophysiological
      recording methods were used to characterize the visual representation and
      cortical area prior to injection of the tracer. Our findings reveal that
      seventeen of the 25 cortical areas project upon some portion of the superficial
      layers (stratum zonale, stratum griseum superficiale, and stratum opticum, SO).
      These cortical regions include areas 17, 18, 19, 20a, 20b, 21a, 21b, posterior
      suprasylvian area (PS), ventral lateral suprasylvian area (VLS), posteromedial
      lateral suprasylvian area (PMLS), anteromedial lateral suprasylvian area (AMLS),
      anterolateral lateral suprasylvian area (ALLS), posterolateral lateral
      suprasylvian area (PLLS), dorsolateral lateral suprasyvian area (DLS),
      periauditory cortex, cingulate cortex, and the visual portion of the anterior
      ectosylvian sulcus. While some of these corticotectal projections target all
      superficial laminae and sublaminae, others are more discretely organized in their
      laminar-sublaminar distribution. Only the corticotectal projections arising from
      areas 17 and 18 are exclusively related to the superficial layers. The remaining
      15 pathways innervate both the superficial and intermediate and/or deep layers.
      The large intermediate gray layer (stratum griseum intermedium; SGI) receives
      projections from almost every cortical area; only areas 17 and 18 do not project
      ventral to SO. All corticotectal projections to SGI vary in their sublaminar
      distribution and in their specific pattern of termination. The majority of these
      projections are periodic, or patchy, and there are elaborate (double tier,
      bridges, or streamers) modes of distribution. We have attempted to place these
      findings into a conceptual framework that emphasizes that the SGI consists of
      sensory and motor domains, both of which contain a mosaic of connectionally
      distinct afferent compartments (Illing and Graybiel, '85, Neuroscience 14:455
      482; Harting and Van Lieshout, '91, J. Comp. Neurol. 305:543-558). Corticotectal
      projections to the layers ventral to SGI, (stratum album intermediale, stratum
      griseum profundum, and stratum album profundum) arise from thirteen cortical
      areas. While an organizational plan of these deeper projections is not readily
      apparent, the distribution of several corticotectal inputs reveals some
      connectional parcellation.

PMID- 1401269
TI  - Further study of the aberrant optic nerve projection to olfactory cortex.
AB  - When implanted into the cerebral hemisphere, the regenerating optic nerve of the
      adult frog (Rana pipiens) forms a well-defined terminal field in the pars
      ventralis of the lateral (olfactory) cortex, and sometimes expands medially into
      the postolfactory eminence. These adjacent areas receive their normal input from
      the main olfactory bulb. The aberrant projection extends caudally toward the core
      neuropil of the medial amygdaloid nucleus, which receives its normal input from
      the accessory olfactory bulb, but does not enter this vomeronasal sector of the
      amygdala. The present study tests whether: 1) optic fibers would innervate the
      vomeronasal amygdala after surgical ablation of the accessory olfactory bulb, 2)
      the projection would transpose into adjacent cortex after olfactory cortex
      lesions, and 3) the projection would overflow into adjacent areas after being
      amplified by hemisection at the di-telencephalic junction (to minimize escape of
      fibers into the diencephalon). The retinal projection always terminated in the
      olfactory cortex when this area was intact, or in spared fragments of it after
      radical cortical lesions, but never entered the vomeronasal amygdala in any
      specimen, as studied by autoradiographic and horseradish peroxidase tracing
      techniques. With forebrain hemisection, the cortical terminal field increased in
      thickness but remained confined to the olfactory area. However, the interruption
      of the lateral forebrain bundle induced a new projection to the striatum in a
      region neighboring but separate from the olfactory cortical field. These findings
      support the hypothesis that retinal fibers have a specific affinity for primary
      olfactory cortex that is not normally allowed expression in development. Retinal
      fibers may also have a latent affinity for the striatum that is unmasked after
      deafferentation.

PMID- 1401270
TI  - Afferents to the oculomotor nucleus in the goldfish (Carassius auratus) as
      revealed by retrograde labeling with horseradish peroxidase.
AB  - The goal of this work was to compare the distribution and morphology of neurons
      projecting to the oculomotor nucleus in goldfish with those previously described
      in other vertebrate groups. Afferent neurons were revealed by retrograde labeling
      with horseradish peroxidase. The tracer was electrophoretically injected into the
      oculomotor nucleus. The location of the injection site was determined by the
      antidromic field potential elicited in the oculomotor nucleus by electrical
      stimulation of the oculomotor nerve. Labeled axons whose trajectories could be
      reconstructed were restricted to the medial longitudinal fasciculus. In order of
      quantitative importance, the afferent areas to the oculomotor nucleus were: (1)
      the ipsilateral anterior nucleus and the contralateral tangential and descending
      nuclei of the octaval column. Furthermore, a few labeled cells were found
      dorsomedially to the caudal pole of the unlabeled anterior octaval nucleus; (2)
      the contralateral abducens nucleus. The labeled internuclear neurons were
      arranged in two groups within and 500 microns behind the caudal subdivision of
      the abducens nucleus; (3) a few labeled cells were observed in the
      rhombencephalic reticular formation near the abducens nucleus, most of which were
      contralateral to the injection site. Specifically, stained cells were found in
      the caudal pole of the superior reticular nucleus, throughout the medial
      reticular nucleus and in the rostral area of the inferior reticular nucleus; (4)
      eurydendroid cells of the cerebellum, located close to the contralateral
      eminentia granularis pars lateralis, were also labeled; and (5) a small and
      primarily ipsilateral group of labeled cells was located at the mesencephalic
      nucleus of the medial longitudinal fasciculus. The similarity in the structures
      projecting to the oculomotor nucleus in goldfish to those in other vertebrates
      suggests that the neural network involved in the oculomotor system is quite
      conservative throughout phylogeny. Nevertheless, in goldfish these projections
      appeared with some specific peculiarities, such as the cerebellar and
      mesencephalic afferents to the oculomotor nucleus.

PMID- 1401271
TI  - Epidermal dendritic cells in psoriasis possess a phenotype associated with
      antigen presentation: in situ expression of beta 2-integrins.
AB  - BACKGROUND: Epidermal dendritic cells (DCs) isolated from psoriasis possess
      greatly enhanced T lymphocyte-activating properties compared with DCs from normal
      skin, suggesting that DCs in psoriasis express surface antigens crucial for
      antigen presentation. These include beta 2-integrins and intercellular adhesion
      molecule (ICAM)-1. OBJECTIVE: Our purpose was to determine DC phenotype in
      psoriatic compared with normal epidermis with respect to these molecules.
      METHODS: Tissue sections were single labeled with a peroxidase antiperoxidase
      (PAP) immunohistochemical technique and double labeled where necessary with a
      combination of a PAP and an alkaline phosphatase-anti-alkaline phosphatase
      technique. RESULTS: In psoriatic compared with normal skin, decreased numbers of
      DCs expressed CD1a (p less than 0.05), whereas increased numbers of DCs expressed
      class II major histocompatibility antigens (p less than 0.05). In normal skin
      positive staining for CD18 was not observed, whereas in psoriasis both CD1a+ and
      CD1a- DCs expressed beta 2-integrins, LFA-1 (CD11a/CD18), and gp 150/95
      (CD11c/CD18). DCs in atopic dermatitis and lichen planus were also found to
      express beta 2-integrins. Neither MAC 1 (CD11b/CD18) nor ICAM-1 was observed on
      DCs. CONCLUSION: These data are consistent with either migration of dendritic
      antigen-presenting cells into the epidermis or in situ cytokine modulation of
      Langerhans cell phenotype in inflamed skin. Furthermore, they indicate that
      epidermal DCs in psoriasis and other cutaneous inflammatory diseases express
      molecules that are known to be crucial for Langerhans cell-driven T-cell
      activation in vitro.

PMID- 1401272
TI  - Oral lesions in systemic lupus erythematosus. Do ulcerative lesions represent a
      necrotizing vasculitis?
AB  - BACKGROUND: It has been suggested that oral lesions in patients with systemic
      lupus erythematosus (SLE) may be grouped clinically as erythema, discoid lesions,
      or oral ulcerations. Oral ulcerations have been said to foretell a severe
      systemic disease flare and the proposal that oral ulcers represent a mucosal
      vasculitis has been suggested to explain this hypothesis. OBJECTIVE: Our
      objective was to test the hypothesis that oral ulcers in patients with SLE result
      from vasculitis. METHODS: We studied 10 patients with American College of
      Rheumatology (ACR) criteria for a diagnosis of SLE who had oral lesions of lupus
      (six prospectively and four retrospectively) clinically and by routine and
      immunofluorescence microscopy. Biopsy specimens were reviewed in a single-blinded
      fashion. RESULTS: In our patients, no oral lesion, regardless of morphology,
      demonstrated vasculitis histologically. All lesions demonstrated an interface
      mucositis. CONCLUSION: Our data strongly contradict the hypothesis that
      leukocytoclastic vasculitis explains a possible unproven correlation between oral
      ulceration and disease flares in patients with SLE.

PMID- 1401273
TI  - Immunoelectronmicroscopic differentiation of linear IgA bullous dermatosis of
      adults with coexistence of IgA and IgG deposition from bullous pemphigoid.
AB  - BACKGROUND: The differentiation between linear IgA bullous dermatosis (LABD) and
      bullous pemphigoid (BP) is sometimes difficult in patients who have both IgA and
      IgG deposition in a linear pattern at the basement membrane zone. OBJECTIVE: We
      address whether two cases of acquired subepidermal blistering disease with
      coexistence of IgA and IgG deposition in a linear pattern at the basement
      membrane zone are LABD or BP. METHODS: The two cases were investigated by
      immunoelectron microscopy and compared with two typical cases of LABD. RESULTS:
      In both cases, the deposition of IgA and IgG was ultrastructurally localized
      below the lamina densa in close association with anchoring fibrils, as was seen
      in two cases of typical LABD. CONCLUSION: These findings indicate that our two
      cases of acquired blistering disease with co-existence of IgA and IgG deposition
      are LABD, rather than BP.

PMID- 1401274
TI  - Dysplastic nevi can be diagnosed and graded reproducibly: a longitudinal study.
AB  - BACKGROUND: Poor interobserver reproducibility in diagnosing and grading
      dysplastic melanocytic nevi is often cited as evidence against the ability of
      pathologists to recognize such an entity. OBJECTIVE: We attempted to examine the
      diagnostic profiles of melanocytic lesions of two dermatopathologists in a stable
      population base. METHODS: All 2600 melanocytic neoplasms were diagnosed at
      Stanford University Medical Center during the past 4 years by one
      dermatopathologist from 1987 to 1989 and a different dermatopathologist in 1990
      and 1991. The two independently evaluated these lesions unaware of the other's
      criteria. RESULTS: The diagnostic profile of the two pathologists shows a
      striking degree of similarity: 76.7% versus 75.3% of all nevi were diagnosed as
      acquired melanocytic nevi, 8.8% versus 12.0% were diagnosed as mildly dysplastic,
      7.0% versus 6.8% as moderately dysplastic, and 2.7% versus 1.6% as severely
      dysplastic. CONCLUSION: Our findings suggest that the two pathologists are using
      reproducible criteria for diagnosing and grading dysplastic nevi.

PMID- 1401275
TI  - The Tzanck smear: can dermatologists accurately interpret it?
AB  - BACKGROUND: The Tzanck preparation is a standard technique for the rapid
      diagnosis of herpes simplex and varicella-zoster virus infections. OBJECTIVE:
      This study was designed to determine the ability of practicing dermatologists to
      interpret Tzanck preparations accurately. METHODS: Dermatologists at different
      levels of training interpreted a series of Tzanck preparations under test
      conditions. RESULTS: Second- and third-year residents had a pooled average for
      correct responses of 91%; dermatologists in practice less than 10 years, 84%;
      dermatologists in practice more than 10 years, 67%. CONCLUSION: Dermatologists
      are able to use the Tzanck preparation effectively for diagnosing herpetic
      infections. Second- and third-year residents who are most likely to be diagnosing
      blistering eruptions in immunosuppressed or otherwise critically ill patients are
      especially accurate interpreters.

PMID- 1401276
TI  - Cutaneous Bowen's disease. An analysis of 1001 cases according to age, sex, and
      site.
AB  - BACKGROUND: There are no large studies of Bowen's disease that have analyzed its
      distribution according to age, sex, and site. OBJECTIVE: This study was performed
      primarily to determine whether there were significant sex and site differences in
      the distribution of Bowen's disease. METHODS: One thousand one skin biopsy
      specimens of Bowen's disease were analyzed according to age, sex, and site of
      origin. RESULTS: This study revealed that the most common site of Bowen's disease
      was the head and neck (440 lesions), whereas specimens from the lower limbs (298
      lesions) and upper limbs (198 lesions) outnumbered specimens from the torso (65
      lesions). Of 298 specimens from the lower limbs, 72.1% were from women; 79.3% of
      the 87 specimens from the scalp and ears were from men. Eighty percent of the 85
      specimens of Bowen's disease from the cheeks were from women. CONCLUSION: These
      results indicate that cutaneous Bowen's disease occurs mainly on sun-exposed
      sites. This is also supported by the predominance of Bowen's disease on the lower
      limbs in women and on the scalp and ears in men. The basis for the female
      predominance on the cheeks is unknown, but may reflect the increased
      vulnerability to sun damage of superficial vellus hair follicles that predominate
      on the cheeks in women. This finding may provide indirect support for the
      hypothesis that some forms of Bowen's disease have a follicular histogenesis.

PMID- 1401277
TI  - Serum adenosine deaminase activity in systemic sclerosis (scleroderma) and
      related disorders.
AB  - BACKGROUND: Adenosine deaminase (ADA) activity in serum is mainly derived from T
      lymphocytes. OBJECTIVE: Our purpose was to clarify the significance of ADA
      activity in systemic sclerosis (PSS) and related disorders. METHODS: ADA activity
      was determined with an enzymatic method in 34 patients with PSS, 4 with mixed
      connective tissue disease (MCTD), 6 with dermatomyositis (DM), 11 with localized
      scleroderma (LS), and 13 with other collagen diseases. RESULTS: Serum ADA
      activity was elevated over the mean (+2 standard deviations) of the control in
      85% of the patients with PSS, all with MCTD, 83% of those with DM, and 82% of
      those with LS. The mean values in 10 PSS patients with anti-topoisomerase I
      antibodies, 14 patients with anti-RNP antibodies, 12 patients with anticentromere
      antibodies (ACAs), and 5 patients without antinuclear antibodies (ANAs) were
      26.1, 24.9, 22.6, and 16.8 IU/L, respectively. In most cases, except for ACA
      positive patients, serum ADA activity changed almost in parallel with ANA titers.
      CONCLUSION: These results support the notion that T cells are involved in the
      pathogenesis of PSS and related disorders.

PMID- 1401278
TI  - Perineal ecthyma gangrenosum in infancy and early childhood: septicemic and
      nonsepticemic forms.
AB  - BACKGROUND: Ecthyma gangrenosum is characterized by necrotic ulcerations
      surrounded by an erythematous halo. It is secondary to Pseudomonas aeruginosa
      infection. Most lesions are located in the anogenital and axillary areas, but the
      route of infection is generally difficult to establish. OBJECTIVE: We report six
      children with perineal ecthyma gangrenosum and discuss predisposing factors,
      origin, and route of infection. METHODS: This was a retrospective clinical study.
      RESULTS: Three children had blood cultures positive for P. aeruginosa, and one
      died. Predisposing factors were present in all cases; two had received
      chemotherapy (neuroblastoma, acute lymphoblastic leukemia), and two had
      idiopathic granulocytopenia. The last two patients previously had received
      treatment with systemic antibiotics and had abnormal granulocyte killing several
      months later. CONCLUSION: Septicemic ecthyma gangrenosum can be rapidly fatal in
      young children and requires aggressive antibiotic therapy. Benign ecthyma
      gangrenosum in healthy infants may result from a modification of bowel microflora
      after antibiotic therapy in conjunction with maceration in the diaper area.
      However, careful evaluation and long-term follow-up must be done to detect
      neutropenia, functional abnormalities of granulocytes, or a possible immune
      deficiency.

PMID- 1401279
TI  - Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal
      photochemotherapy.
AB  - BACKGROUND: This original cohort of patients with erythrodermic cutaneous T-cell
      lymphoma (CTCL) was reported to have clinical improvement with photopheresis
      during the 12 months of the original study. No long-term follow-up data have been
      available to examine the impact of this therapy on the disease. OBJECTIVE: Our
      purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL
      patients treated with photopheresis and to compare these results with historical
      controls. METHODS: Files of patients from the original photopheresis study
      centers were reviewed and their current status was documented. RESULTS: The
      median survival of the treated patients was 60.33 months from the date of
      diagnosis and 47.9 months from the date of the start of photopheresis therapy. A
      complete remission has been maintained in four of the six patients who achieved
      complete responses in the original study. The best responses were seen in
      patients with a lower CD4/CD8 ratio in the peripheral blood at the start of
      therapy. CONCLUSION: Photopheresis can influence the natural history of
      erythrodermic CTCL by inducing remissions and prolonging survival with minimal
      toxicity.

PMID- 1401280
TI  - Elevation of fasting serum lipids in patients treated with low-dose cyclosporine
      for severe plaque-type psoriasis. An assessment of clinical significance when
      viewed as a risk factor for cardiovascular disease.
AB  - BACKGROUND: Hyperlipidemia has received little attention as a side effect of
      cyclosporine therapy for severe psoriasis. OBJECTIVE: We report changes in
      fasting serum lipids in patients treated with low-dose oral cyclosporine for
      psoriasis and discuss their significance. METHODS: Twenty-two patients with
      severe, recalcitrant, plaque-type psoriasis were treated with cyclosporine, 5
      mg/kg/day, for 12 to 16 weeks. Fasting serum lipid levels (triglycerides,
      cholesterol, and high-density lipoproteins) were measured at 2-week intervals.
      RESULTS: The mean serum triglyceride level increased from 117.8 +/- 11.7 mg/dl
      before initiation of therapy to 183.9 +/- 31.4 mg/dl after 2 weeks of treatment,
      without further significant change during the remainder of the study (p less than
      0.007). A significant elevation of serum cholesterol from 207.1 +/- 8.1 mg/dl
      initially to 247.4 +/- 10.2 mg/dl after 2 weeks of treatment occurred (p less
      than 0.001) and persisted with continued cyclosporine therapy. No consistent
      alteration in high-density lipoprotein was noted (p less than 0.42). CONCLUSION:
      Serum lipids should be closely monitored in psoriasis patients receiving
      intermediate or long-term therapy with cyclosporine, especially in the presence
      of elevated baseline values.

PMID- 1401281
TI  - Dermabrasion: therapy and prophylaxis of the photoaged face.
AB  - BACKGROUND: For many years dermabrasion has been used for the treatment of
      photoaged facial skin. However, there is a paucity of correlative studies that
      document the beneficial histopathologic effects of dermabrasion with clinical
      changes. Moreover, long-term follow-up and comparative studies that document
      these therapeutic results are lacking. OBJECTIVE: Our purpose was to study
      patients with photoaged facial skin by comparing the preoperative and
      postoperative clinical and histopathologic changes that occur as a result of
      surgical dermabrasion of aged and photodamaged facial skin. METHODS: Twelve
      patients 40 years of age and older with significant photoaging and
      dermatoheliosis were treated with full-face dermabrasion. Predermabrasion biopsy
      specimens were compared with matched postdermabrasion biopsy specimens taken at
      various time intervals from 6 months to 8 years after dermabrasion. RESULTS:
      Microscopic normalization of the actinically damaged epidermis and papillary
      dermis was manifested clinically by the replacement of dermatoheliosis with
      supple, smooth-textured facial skin that remained clinically evident well beyond
      8 years after dermabrasion. In addition, the necessity for the continued
      treatment of premalignant and malignant lesions was virtually eliminated during
      the 8-year postdermabrasion period. CONCLUSION: Not only is dermabrasion a
      beneficial therapeutic option for aged and photo-damaged skin, but it also is a
      valid means of prophylaxis against neoplastic changes.

PMID- 1401282
TI  - Epidermodysplasia verruciformis associated with severe immunodeficiency,
      lymphoma, and disseminated molluscum contagiosum.

PMID- 1401283
TI  - Clearance of unremitting psoriasis after treatment with granulocyte-macrophage
      colony-stimulating factor.

PMID- 1401285
TI  - Intraosseous epidermoid cysts.

PMID- 1401284
TI  - Acantholytic acanthomas in an immunosuppressed patient.

PMID- 1401286
TI  - Petechiae caused by streptococcal pharyngitis.

PMID- 1401287
TI  - Lymphocytoma cutis induced by gold pierced earrings.

PMID- 1401288
TI  - Pulmonary and cutaneous tuberculosis.

PMID- 1401289
TI  - Large granular lymphocytes within the epidermis of erythema multiforme lesions.

PMID- 1401290
TI  - Successful treatment of disseminated cutaneous sporotrichosis with ketoconazole.

PMID- 1401291
TI  - Amelanotic melanoma presenting as inflammatory plaques.

PMID- 1401292
TI  - Koplik spots and a purpuric eruption associated with parvovirus B19 infection.

PMID- 1401293
TI  - Linear focal elastosis: a degenerative or regenerative process of striae
      distenae?

PMID- 1401295
TI  - Necrolytic migratory erythema without glucagonoma.

PMID- 1401294
TI  - A primer on cosmetics. AAD Advisory Board, CTFA Task Force on Cosmetics.

PMID- 1401296
TI  - Lyme disease in Israel.

PMID- 1401297
TI  - Leg ulcers.

PMID- 1401298
TI  - Leg ulcers.

PMID- 1401299
TI  - Leg ulcers.

PMID- 1401300
TI  - Hypertriglyceridemia in patients with psoriasis treated with cyclosporine.

PMID- 1401301
TI  - Wiskott-Aldrich syndrome: new molecular and biochemical insights.
AB  - The Wiskott-Aldrich syndrome is an uncommon X-linked recessive disease
      characterized by eczema, thrombocytopenia, and immunodeficiency. The clinical
      features begin early in life and include recurrent infections, bleeding, and
      severe eczema. Unless the condition is treated by bone marrow transplantation,
      the prognosis of Wiskott-Aldrich syndrome is grave, and premature death caused by
      sepsis, hemorrhage, or lymphoreticular malignancy is common. Although the
      biochemical defect responsible for the syndrome is not known, recent
      investigations with restriction fragment length polymorphisms have mapped the
      Wiskott-Aldrich syndrome locus to the proximal portion of the short arm of the
      human X chromosome (Xp11). The isolation of these DNA markers makes feasible both
      carrier detection and prenatal diagnosis of Wiskott-Aldrich syndrome and provides
      an important adjunct to the management of Wiskott-Aldrich syndrome for patients
      and their families. These genetic data, in conjunction with the recent
      identification of a specific O-glycosylation defect in lymphocytes from patients
      with Wiskott-Aldrich syndrome, present an opportunity for the eventual isolation
      of the Wiskott-Aldrich syndrome gene and identification of the underlying
      cellular defect. We review the clinical and laboratory features of this syndrome
      and summarize the new molecular and biochemical approaches that can be used in
      diagnosis, genetic counseling, and treatment.

PMID- 1401302
TI  - Reactive lentiginous hyperpigmentation after cryosurgery for lentigo maligna.
AB  - BACKGROUND: Twenty patients treated for lentigo maligna of the face with
      cryosurgery developed benign lentiginous hyperpigmentation mimicking a
      recurrence. OBJECTIVE: When cryosurgery is used in the treatment of lentigo
      maligna, it is important to know whether repigmentation of the scar represents
      true recurrence or a benign process. METHODS: Twenty patients were treated with
      cryosurgery for lentigo maligna of the face. Within a follow-up period of 7 to 80
      months, frequent clinical observations were made. RESULTS: Lentiginous
      hyperpigmentation developed within the treatment area in eight patients.
      Histologic investigation revealed recurrence of lentigo maligna in three and
      benign hyperpigmentation in five. CONCLUSION: Genetic factors and UV exposure
      after cryosurgery may favor the development of benign lentiginous
      hyperpigmentation. Because recurrence of lentigo maligna must be considered,
      histologic evaluation of repigmentation is mandatory.

PMID- 1401303
TI  - Pulsed-dye laser therapy for cutaneous Kaposi's sarcoma associated with acquired
      immunodeficiency syndrome.
AB  - BACKGROUND: Cutaneous lesions of Kaposi's sarcoma associated with acquired
      immunodeficiency syndrome (AIDS-KS) are disfiguring. OBJECTIVE: This study
      assesses the response of AIDS-KS to pulsed-dye laser (PDL) therapy. METHODS: The
      PDL was used to treat 15 AIDS-KS patients. Treatment was repeated at 4-week
      intervals. On average, patients received three treatments per treated lesion.
      RESULTS: At 6 weeks' follow-up, the patients' treated lesions were reduced in
      size when compared with their matched control lesions (p less than 0.002). A
      complete or partial clinical response occurred in 44% of treated lesions (17 of
      39) compared with 18% of matched control lesions (7 of 39) [corrected]. Patients
      experienced limited pain, infrequent blistering, and no scarring. However,
      histopathologic findings of treated lesions throughout therapy correlated poorly
      with clinical response. At 12 weeks, all treated lesions had recurred.
      CONCLUSION: PDL therapy for AIDS-KS is not recommended. Although safe, the rapid
      recurrence of disease at initially responsive sites would require costly, long
      term therapy to maintain cosmetic improvement.

PMID- 1401304
TI  - Combination of patch test and IgE for dust mite antigens differentiates 130
      patients with atopic dermatitis into four groups.
AB  - BACKGROUND: Patients with atopic dermatitis sometimes have positive responses to
      patch testing (PT) with dust mite antigens, which is believed to correlate with
      the elevated levels of specific IgE for those antigens. OBJECTIVE: The purpose of
      this study is to identify the correlation between the PT and serum IgE concerning
      the mite antigens. METHODS: We studied 130 patients with atopic dermatitis by the
      PT reaction and the serum level of specific IgE for Dermatophagoides
      pteronyssinus antigens. RESULTS: Fifty-one of the 130 patients assessed as PT
      positive had either high (32 of 130 patients; 24.6%) or low or no (19 of 130
      patients; 14.6%) levels of mite-specific IgE; there was a significant difference
      between the groups with elevated and low IgE. Similarly, a total of 79 PT
      negative patients also showed an elevated or low mite-specific IgE (42 of 130
      patients [32.3%] or 37 of 130 patients [28.5%], respectively). It was noted that
      clinical morphologic findings were peculiar to three of the four groups; however,
      the patients who were PT-negative with a low IgE (37 of 130 patients) showed no
      particular clinical lesions. CONCLUSION: Comparing the results from our 130
      patients, there was no correlation between the serum IgE level and the PT
      reaction for dust mite antigens. Conversely, the results of PT and mite-specific
      IgE could be used to divide these patients into four distinct groups, each with
      its own particular clinical morphology, suggesting the heterogeneity of this
      disease.

PMID- 1401305
TI  - Paraneoplastic pemphigus: a report of three cases including one long-term
      survivor.
AB  - BACKGROUND: Paraneoplastic pemphigus is a newly described autoimmune disease
      characterized by painful mucosal ulcerations and polymorphous skin lesions in
      association with an underlying neoplasm. All reported patients with an associated
      malignant neoplasm have had a poor prognosis. OBJECTIVE: We present three new
      cases of paraneoplastic pemphigus associated with a malignant neoplasm and
      further characterize this disease. METHODS: We used clinical criteria, histologic
      and immunopathologic examinations, and immunophenotyping to characterize this
      disease. In addition, we performed immunoprecipitation studies with extracts of
      radiolabeled human keratinocytes to characterize the antigens to which patient
      serum binds. RESULTS: All three patients had clinical, histologic, and
      immunopathologic findings that were strongly suggestive of paraneoplastic
      pemphigus. Their sera immunoprecipitated a complex of four polypeptides from
      human keratinocyte extracts with molecular weights of 250, 230, 210, and 190 kd,
      confirming the diagnosis of paraneoplastic pemphigus. The 250, 230, and 210 kd
      antigens comigrated with desmoplakin I, the 230 kd bullous pemphigoid antigen,
      and desmoplakin II, respectively. Lymphocyte immunophenotyping revealed large
      populations of monoclonal CD19+, CD5+ B cells in two cases. Although two of the
      patients died, one patient is alive and well 2 years after the diagnosis of
      paraneoplastic pemphigus. CONCLUSION: We report three cases of paraneoplastic
      pemphigus. One patient is alive and well 2 years after diagnosis, which suggests
      that a subgroup of patients may have a more benign course.

PMID- 1401306
TI  - Malignant lymphoma and leukemia with prominent ulceration: clinicopathologic
      correlation of 33 cases.
AB  - BACKGROUND: The clinical and pathologic findings in patients with malignant
      lymphomas who presented with prominent cutaneous ulcers are described. OBJECTIVE:
      Our purpose was to determine the histologic findings, type, and prognosis of
      lymphomas with cutaneous ulcers. METHODS: Thirty-three patients (20 with
      cutaneous T-cell lymphomas, 10 with other non-Hodgkin's lymphomas, and 3 with
      leukemia) were retrospectively studied. RESULTS: All patients had a poor
      prognosis; 23 died within 9 months after the onset of the ulcers. Patients with
      non-Hodgkin's lymphoma had a worse prognosis, had a higher incidence of systemic
      involvement, and more often had ulcers as an initial manifestation of lymphoma
      than did the patients with cutaneous T-cell lymphoma. The histopathologic
      findings ranged from a nonspecific inflammatory infiltrate to ulcers with marked
      adjacent epidermal epidermotropism to ulcers with an angiocentric infiltrate.
      CONCLUSION: A variety of lymphomas may cause cutaneous ulceration. Adequate
      sampling of these ulcers is necessary for diagnosis. The average life expectancy
      after ulcer formation is 21 months.

PMID- 1401308
TI  - Photographic utilization in dermatology clinics in the United States: a survey of
      university-based dermatology residency programs.
AB  - BACKGROUND: Photography has recently been introduced as an adjunct to the
      clinical management of patients with the dysplastic nevus syndrome (DNS).
      OBJECTIVE: Our purpose was to evaluate the methods used and the extent of
      clinical photography in dermatology residency programs in the United States.
      METHODS: Nonmilitary accredited dermatology residency programs in the United
      States were surveyed (73% response rate) regarding utilization and technical
      aspects of clinical photography. RESULTS: Forty-one percent of respondents used
      photography for the clinical management of 90% or more of patients with DNS.
      Twenty-four percent of respondents used photography for the clinical management
      of all patients with DNS. Eighty-one percent of respondents used slides, and 62%
      utilized total body photographs. The median number of photographs taken for a
      patient with DNS was 20. CONCLUSION: Dermatologic photography has been widely
      adopted for the clinical management of patients with DNS. Failure of the health
      insurance industry to recognize the value of this procedure may result in its
      underutilization.

PMID- 1401307
TI  - Stratum corneum changes in patients with senile pruritus.
AB  - BACKGROUND: Generalized pruritus in the elderly is a common and distressing
      problem; often there is no evidence of skin disease other than xerosis.
      OBJECTIVE: The aim of the study was to determine whether any abnormality could be
      detected in the structure and function of the skin of patients with generalized
      pruritus. METHODS: The skin of 13 elderly patients with generalized pruritus,
      without skin disease or any underlying cause, was contrasted with that of age-
      and sex-matched normal control subjects. RESULTS: The patients had clinically
      drier skin (mean visual analogue scale score 2.9 [standard deviation +/- 2.2],
      controls 0.52 [+/- 0.59], p = 0.002). The severity of the pruritus was related to
      the degree of xerosis (r = 0.66). The patients had decreased skin surface
      conductance (10.7 mumho [+/- 3.4], controls 16 mumho [+/- 5.3], p = 0.017), and
      increased intracorneal cohesion (240.5 g [+/- 88], controls 162.7 g [+/- 39.8], p
      = 0.001). The patients also had statistically significantly diminished parameters
      of skin surface contour. CONCLUSION: The findings of increased intracorneal
      cohesion and altered skin surface contour parameters suggest that elderly
      patients with generalized pruritus may have an acquired abnormality of
      keratinization.

PMID- 1401310
TI  - The focal facial dermal dysplasias: report of a kindred and a proposed new
      classification.
AB  - BACKGROUND: The focal facial dermal dysplasias (FFDD) are a genetically
      heterogeneous group of disorders characterized by congenital bilateral scarlike
      facial lesions, with or without associated facial anomalies. The cases have been
      reported under various names; thus the nosology is confusing and unclear.
      OBJECTIVE: Our purposes were to report our kindred, clearly delineate the various
      types of FFDD reported, and propose a new simplified classification. METHODS: The
      clinical and histologic changes were examined and genealogy determined for our
      kindred. The medical literature was reviewed and the reported cases reexamined
      and categorized according to their clinical features and inheritance patterns.
      RESULTS: We determined that there are three distinct varieties of FFDD: type I,
      autosomal dominant FFDD; type II, autosomal recessive FFDD; and type III, FFDD
      with other facial features. CONCLUSION: We propose a new classification and
      provide evidence for three distinct varieties of FFDD: type I, autosomal dominant
      FFDD; type II, autosomal recessive FFDD; and type III, FFDD with other facial
      features (Setleis syndrome). Our kindred represents type II.

PMID- 1401309
TI  - Differential effects of cyclosporine and etretinate on serum cytokine levels in
      patients with psoriasis.
AB  - BACKGROUND: The in vivo effects of cyclosporine and etretinate on the immune
      system are still unclear. OBJECTIVE: Our purpose was to determine the effects of
      these drugs on in vivo production of various cytokines. METHODS: Serum cytokine
      levels were measured sequentially by radioimmunoassay in psoriasis patients
      treated with either cyclosporine or etretinate. RESULTS: Interferon-gamma levels
      were initially elevated and rapidly returned to baseline levels before clinical
      improvement in both treatment groups. A transient increase before the relapse was
      also observed in some patients. Etretinate treatment resulted in a substantial
      decrease in tumor necrosis factor-alpha levels, whereas an unpredictable increase
      was found during the late phase of cyclosporine treatment. CONCLUSION: The in
      vivo effects of antipsoriatic drugs on cytokine production are different from
      those demonstrated in vitro. Measurement of serum cytokine levels is useful for
      monitoring patients with psoriasis.

PMID- 1401312
TI  - Current dermatologic therapy.
AB  - This article reviews therapeutic advances reported in the English-language
      literature during 1991. Readers should review the original article in full before
      attempting any experimental or controversial therapy.

PMID- 1401311
TI  - Cyclosporine therapy for psoriasis: a cell cycle-derived dosing schedule.
AB  - BACKGROUND: Cyclosporine is effective in the treatment of psoriasis; however,
      potentially serious side effects limit its long-term use. On the basis of the 36
      hour psoriatic keratinocyte cell cycle, a new dosing regimen was investigated.
      OBJECTIVE: The purpose of this study was to evaluate a 36-hour weekly dosing
      schedule with cyclosporine for the treatment of psoriasis, in an attempt to
      decrease side effects while maintaining efficacy. METHODS: Fifteen patients were
      studied by means of oral doses of cyclosporine taken at 12-hour intervals for
      three doses per week during a 10-week period. The initial dose, 2.5 mg/kg/dose
      (7.5 mg/kg/wk), was increased every 2 weeks by 2.5 mg/kg/dose to a maximum of 10
      mg/kg/dose. RESULTS: The average improvement as assessed by the Psoriasis Area
      and Severity Index for all 15 patients was 61%. Six patients had a more than 75%
      improvement, three patients improved 50% to 74%, and six patients improved less
      than 50%. Three patients dropped out because of adverse side effects, and three
      others completed the study at a reduced dose. CONCLUSION: It is concluded that,
      although effective, this dosing regimen may not have an advantage over daily
      dosing, given its side effect profile and the need to go to relatively high doses
      every 24 hours.

PMID- 1401313
TI  - Alkaptonuria and ochronosis: case report and review.
AB  - Alkaptonuria is a rare genetic disorder in which the enzyme homogentisic acid
      oxidase is deficient, resulting in the accumulation of homogentisic acid in
      various bodily tissues. This is a multisystem disorder with a characteristic blue
      black discoloration of the skin and cartilage, which is termed ochronosis. Herein
      we report a profound case of ochronosis secondary to alkaptonuria. Furthermore,
      we review the clinical manifestations of alkaptonuria and discuss the spectrum of
      ochronosis, both endogenous and exogenous.

PMID- 1401314
TI  - Androgen insensitivity syndrome (testicular feminization): a model for
      understanding steroid hormone receptors.
AB  - Testicular feminization, a syndrome of end-organ androgen resistance, has been
      characterized at the molecular level. Well-defined mutations in the androgen
      receptor have been identified in this disorder. This receptor belongs to a family
      of intracellular hormone receptors, which includes receptors for corticosteroids,
      mineralocorticoids, sex hormones, vitamin D3, thyroid hormone, and retinoids. An
      understanding of the structure and molecular defects identified for the androgen
      receptor serves as a model to understand this entire class of receptors, a group
      directly involved in the biochemical pathways of a wide variety of dermatologic
      therapeutic interventions.

PMID- 1401315
TI  - Pellagra complicating Crohn's disease.

PMID- 1401316
TI  - Reversible ectropion after long-term use of topical tretinoin on photodamaged
      skin.

PMID- 1401317
TI  - Steroid-responsive pyoderma gangrenosum with vulvar and pulmonary involvement.

PMID- 1401318
TI  - Topical cyclosporine in chronic benign familial pemphigus (Hailey-Hailey
      disease).

PMID- 1401319
TI  - Pustular lymphomatoid papulosis in childhood.

PMID- 1401320
TI  - Treatment of recalcitrant cheilitis granulomatosa with metronidazole.

PMID- 1401321
TI  - Alopecia universalis in a patient seropositive for the human immunodeficiency
      virus.

PMID- 1401322
TI  - Tinea corporis gladiatorum: an epidemic of Trichophyton tonsurans in student
      wrestlers.

PMID- 1401323
TI  - Fusidic acid cream in the treatment of plasma cell balanitis.

PMID- 1401324
TI  - Successful treatment of aggressive pyoderma gangrenosum with pulse steroids and
      chlorambucil.

PMID- 1401326
TI  - Lichen planus of the eyelid: an unusual clinical presentation.

PMID- 1401325
TI  - Hemorrhagic bullae in association with Enterobacter cloacae septicemia.

PMID- 1401327
TI  - History of the treatment of psoriasis.
AB  - This article reviews the history of selected therapeutic agents for psoriasis:
      arsenic (including Fowler's solution), ammoniated mercury, chrysarobin and
      anthralin, tars, aminopterin and methotrexate, and corticosteroids. The
      developers of these drugs paved the way for the new and improved treatments
      available today for the treatment of psoriasis.

PMID- 1401328
TI  - Multicenter clinical drug trials: should single centers publish their results
      independently?

PMID- 1401329
TI  - Lichen planus.

PMID- 1401331
TI  - Allergic contact dermatitis to natural latex.

PMID- 1401330
TI  - Broad-spectrum protection in sunscreen products.

PMID- 1401332
TI  - Carcinogenicity of topical mechlorethamine in mice.

PMID- 1401333
TI  - The energetic cost of protein synthesis in isolated hepatocytes of rainbow trout
      (Oncorhynchus mykiss).
AB  - To establish the energetic cost of protein synthesis, isolated trout hepatocytes
      were used to measure protein synthesis and respiration simultaneously at a
      variety of temperatures. The presence of bovine serum albumin was essential for
      the viability of isolated hepatocytes during isolation, but, in order to measure
      protein synthesis rates, oxygen consumption rates and RNA-to-protein ratios, BSA
      had to be washed from the cells. Isolated hepatocytes were found to be capable of
      protein synthesis and oxygen consumption at constant rates over a wide range of
      oxygen tension. Cycloheximide was used to inhibit protein synthesis. Isolated
      hepatocytes used on average 79.7 +/- 9.5% of their total oxygen consumption on
      cycloheximide-sensitive protein synthesis and 2.8 +/- 2.8% on maintaining ouabain
      sensitive Na+/K(+)-ATPase activity. The energetic cost of protein synthesis in
      terms of moles of adenosine triphosphate per gram of protein synthesis decreased
      with increasing rates of protein synthesis at higher temperatures. It is
      suggested that the energetic cost consists of a fixed (independent of synthesis
      rate) and a variable component (dependent on synthesis rate).

PMID- 1401334
TI  - Cellular mechanisms of paired electrical stimulation in ferret ventricular
      myocardium: relationship between myocardial force and stimulus interval change.
AB  - The subcellular mechanisms of twitch-force potentiation with paired electrical
      stimulation was studied in ferret ventricular myocardium using the bioluminescent
      calcium indicator aequorin. It is demonstrated for the first time that
      interpolation of an extrasystole in a train of conditioned twitches results in a
      beat-to-beat change in [Ca2+]i and force. Steady-state twitch force and Ca2+i
      were increased with paired stimulation. Increased [Ca2+]o in the setting of
      paired stimulation resulted in an increase in the amplitude of the
      postextrasystole and associated Ca2+ transient. Verapamil, a Ca2+ channel
      antagonist, had the opposite effect of increased [Ca2+]o. Postextrasystole
      potentiation was still present, but diminished in amplitude. These results
      indicate that postextrasystole potentiation is in part due to a verapamil
      depletable store (Ca2+). Postextrasystole potentiation is therefore predominantly
      dependent on sarcoplasmic reticulum (SR) Ca2+ loading. Ryanodine, an alkaloid
      which induces Ca2+ leakage from the SR, abolished postextrasystole potentiation;
      however, in the presence of ryanodine the extrasystole was potentiated. Caffeine,
      a phosphodiesterase inhibitor which induces SR Ca2+ release and impairs uptake,
      also abolished postextrasystole potentiation. As with ryanodine there was
      resultant potentiation of the extrasystole. In the case of caffeine the calcium
      transient consisted of a second slow component associated with extrasystole
      twitch potentiation. The results are consistent with sarcolemmal Ca2+ influx
      playing a role in potentiation of the extrasystole in the presence of an impaired
      SR. These data indicate that transsarcolemmal Ca2+ influx in the presence of
      impaired intracellular Ca2+ buffering can directly activate the myofilaments in
      agreement with reports on human myocardium.

PMID- 1401335
TI  - Effects of starvation on valine and alanine transport across the intestinal
      mucosal border in sea bass, Dicentrarchus labrax.
AB  - Kinetics of intestinal transport of L-alanine and L-valine (substrates of the A
      system and the L-system, respectively, in mammals) across the brush-border
      membrane in sea bass, Dicentrarchus labrax, were studied on intact mucosa using a
      short-term uptake technique. When fish were starved for 4-8 weeks, total influx
      (mucosa-to-cell) of valine fell owing to disappearance or modification of the
      diffusion component. The maximum influx rate of saturable component increased but
      its affinity (reflected by the Michaelis constant) decreased. Alanine transport
      by Na(+)-dependent and diffusion pathways was unchanged after starvation. Fasting
      also induced an almost 20% decrease in the length of intestinal microvilli.

PMID- 1401336
TI  - Effects of eel atrial natriuretic peptide on NaCl and water transport across the
      intestine of the seawater eel.
AB  - Eel atrial natriuretic peptide inhibited the serosa-negative transepithelial
      potential difference and short-circuit current, accompanied by a decrease in NaCl
      and water absorption across the seawater eel intestine. Similar effects were
      obtained after treatment with N-terminally truncated eel atrial natriuretic
      peptide (5-27), indicating that N-terminal amino acids are not essential for the
      action of eel atrial natriuretic peptide. Although mammalian atrial natriuretic
      peptides also inhibited the short-circuit current, a 100-fold higher
      concentration was required to obtain the same effect as with eel atrial
      natriuretic peptide, indicating that eel atrial natriuretic peptide is 100 times
      as potent in eel intestine as the mammalian atrial natriuretic peptides.
      Similarly, in mammalian atrial natriuretic peptide, the four N-terminal amino
      acids had no significant effects. However, when the C-terminal tyrosine was
      removed, the potency of rat atrial natriuretic peptide was lowered. Compared with
      the effects of acetylcholine, serotonin and histamine, eel atrial natriuretic
      peptide was the most potent inhibitor, with 100% inhibition at 10(-7) M; 50%
      inhibition was obtained at 10(-2) M in acetylcholine, and 30% inhibition in
      serotonin (10(-5) M) and histamine (10(-3) M). These inhibitory effects of eel
      atrial natriuretic peptide were not diminished even in the presence of
      tetrodotoxin, and were mimicked by 8-bromoguanosine 3',5'-cyclic monophosphate.
      Based on these results, structure-activity relationships of eel atrial
      natriuretic peptide and a possible mechanism of action of eel atrial natriuretic
      peptide are discussed.

PMID- 1401337
TI  - Metabolic rate during foraging in the honeybee.
AB  - The metabolic rate of free-flying honeybees, Apis mellifera ligustica, was
      determined by means of a novel respirometric device that allowed measurement of
      CO2 produced by bees foraging under controlled reward at an artificial food
      source. Metabolic rate increased with reward (sugar flow rate) at the food
      source. In addition, there was no clear-cut dependence of metabolic rate on load
      carried during the visit, neither as crop load nor as supplementary weights
      attached to the thorax. The hypothesis that metabolic rate, as well as foraging
      and recruiting activities, depend on the motivational state of the foraging bee
      determined by the reward at the food source is discussed.

PMID- 1401340
TI  - Energy metabolism in potoroine marsupials.
AB  - Fasting and fed metabolic rates were measured in three species of potoroine
      marsupials, the rufous rat-kangaroo (Aepyprymnus rufescens), the long-nosed
      potoroo (Potorous tridactylus) and the brush-tailed bettong (Bettongia
      penicillata). There were no significant differences among potoroine species in
      fasting metabolic rate. The lowest fasting heat production for each species was
      11-20% less than the interspecific value of 295 kJ.kg-0.75.day-1 for basal
      metabolism of mature, non-reproductive eutherian homeotherms. The respiratory
      quotient of all species was reduced significantly as starvation proceeded, but
      only for B. penicillata was there a significant effect of starvation duration on
      fasting heat production. The night-time activity of P. tridactylus and B.
      penicillata doubled their daytime fasting heat production; the corresponding
      increase for A. rufescens was only 25%. The calorimetric measurement of fed
      animals showed no differences in digestible energy or metabolisable energy
      between species. Nevertheless, P. tridactylus and B. penicillata produced more
      heat per unit metabolic body mass. The maintenance energy requirements (kJ.kg
      0.75.day-1) were 479, 494 and 345 for P. tridactylus, B. penicillata and A.
      rufescens, respectively. The net availability of metabolisable energy was about
      0.70 in the three species. The combined heat production of fed female A.
      rufescens and their pouch young stayed relatively constant for the first two
      thirds of pouch life, after which it rose sharply (20%) in response to the rapid
      growth of the young. Only during the last week of pouch life did the female enter
      negative energy balance. There was no indication that the metabolism of the
      female increased in response to the presence of a pouch young. The presence of
      pouch young did not alter the efficiency of utilisation of metabolisable energy.
      The daily energy requirement for maintenance was 0.83 MJ.day-1 or 0.36 MJ.kg
      0.75.day-1.

PMID- 1401338
TI  - Glucose metabolism by trout (Salmo trutta) red blood cells.
AB  - Glucose metabolism has been studied in Salmo trutta red blood cells. From non
      metabolizable analogue (3-O-methyl glucose and L-glucose) uptake experiments it
      is concluded that there is no counterpart to the membrane transport system for
      glucose found in mammalian red blood cells. Once within the cells, glucose is
      directed to CO2 and lactate formation through both the Embden-Meyerhoff and
      hexose monophosphate shunts; lactate appears as the most important end-product of
      glucose metabolism in these cells. From experiments under anaerobic conditions,
      and in the presence of an inhibitor of pyruvate transfer to mitochondria, most of
      the CO2 formed appears to derive from the hexose monophosphate pathway.
      Appreciable O2 consumption has been detected, but there is no clear relationship
      between this and substrate metabolism. Key enzymes of glucose metabolism,
      hexokinase, fructose-6-phosphate kinase and, probably, pyruvate kinase are out of
      equilibrium, confirming their regulatory activity in Salmo trutta red blood
      cells. The presence of isoproterenol, a catecholamine analogue, induces important
      changes in glucose metabolism under both aerobic and anaerobic conditions, and
      increases the production of both CO2 and lactate. From the data presented,
      glucose appears to be the major fuel for Salmo trutta red blood cells, showing a
      slightly different pattern of glucose metabolism from rainbow trout red blood
      cells.

PMID- 1401341
TI  - Role of adhesion molecules in cutaneous inflammation and neoplasia.
AB  - There is accumulating evidence that the expression of certain adhesion molecules
      has important consequences for understanding patterns of cell movement in normal
      and pathologically altered skin. This paper reviews recent work regarding the
      role of integrins and other adhesion molecules (ICAM-1, VCAM-1, PECAM-1, LECAM-1,
      and ELAM-1) in cutaneous inflammation and neoplasia, and presents a unifying
      hypothesis which outlines how sequential expression of cytokines and adhesion
      molecules in evolving inflammation may alter the nature of the cellular response.

PMID- 1401339
TI  - Adrenergic receptors and the regulation of vascular resistance in bullfrog
      tadpoles (Rana catesbeiana).
AB  - Vascular adrenergic sensitivity to exogenous catecholamines was examined in
      tadpoles of the American bullfrog (Rana catesbeiana), ranging from stage III to
      XIV. Central arterial blood pressure was measured in decerebrate bullfrog
      tadpoles to determine a reasonable initial infusion pressure. Solutions of
      epinephrine and phenylephrine were infused into the vasculature of pithed
      tadpoles, and the resulting changes in vascular resistance (Rv) were used to
      construct log dose-response relationships. Epinephrine infusion produced a dose
      dependent increase in Rv (EC50 = 5.3 x 10(-7) M), which could be reversed by
      sodium nitroprusside (a smooth muscle relaxant) and blocked by phenoxybenzamine
      (an alpha-adrenergic antagonist). Larval Rv also increased with infusion of the
      alpha-agonist phenylephrine (EC50 = 7.4 x 10(-8) M). Infusion of 10(-6) M
      isoproterenol (a beta-agonist) largely reversed the phenylephrine-induced
      increase in Rv. These results indicate that the capacity exists for both alpha
      mediated vasoconstriction and beta-mediated vasodilation early in bullfrog
      ontogeny. Neither initial Rv nor the responses to infused epinephrine or
      phenylephrine were significantly correlated to development over the range of
      larval stages used in this study.

PMID- 1401343
TI  - In vitro acantholysis induced by D-penicillamine, captopril, and piroxicam on
      dead de-epidermized dermis.
AB  - Drug-induced pemphigus has been recognized for 20 years, but the mechanisms
      leading to acantholysis are still unclear. It has recently been demonstrated that
      penicillamine, captopril, and thiopronin may produce acantholytic lesions, either
      by direct toxic or biochemical effect, in human skin explants. Our work confirms
      that penicillamine and captopril may induce acantholysis on the model of
      keratinocyte culture on dead, de-epidermized dermis. Moreover, it demonstrates
      that piroxicam, a new non-steroidal anti-inflammatory drug, of which one side
      effect is a pemphigus vulgaris-like eruption, is also able to produce in vitro
      acantholysis.

PMID- 1401342
TI  - Deep penetrating (plexiform spindle cell) nevus. A frequent participant in
      combined nevus.
AB  - This report describes 41 patients with lesions similar to those previously termed
      "deep penetrating" or "plexiform spindle cell" nevus (DPN). DPN occurs primarily
      during the first four decades, is somewhat more common in females, and has a
      predilection for the face, trunk, and proximal extremities. It is usually less
      than 1 cm in diameter and often shows variegation in color, including shades of
      brown, blue, and black, that create clinical concern regarding malignant
      melanoma. None of the present tumors nor those from the literature recurred
      following excision. Microscopically, DPN usually has a wedge shape, invariably
      involves reticular dermis, and may penetrate subcutis. Involvement of
      neurovascular structures and adnexae and spread between fibers of the reticular
      dermis create a fascicular-plexiform architecture. The melanocytes are fusiform
      or epithelioid, lightly to moderately pigmented, and exhibit mild to focally
      prominent nuclear atypia. Sparse to abundant melanophages are characteristic.
      Mitotic figures are few and present in only a small minority of lesions. The
      present study of a consecutive series also indicates that DPN is a frequent
      participant in combined nevus, as it was associated with ordinary nevus in two
      thirds of the lesions.

PMID- 1401344
TI  - Histologic features of cutaneous sinus histiocytosis (Rosai-Dorfman disease):
      study of cases both with and without systemic involvement.
AB  - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a
      systemic proliferation of cells that resemble the sinus histiocytes of lymph
      nodes. Whereas initial reports highlighted the often striking cervical
      adenopathy, more than 40% of patients have extranodal involvement. Cutaneous
      lesions are the most common form of extranodal disease, but cases that present as
      cutaneous disease without lymph node involvement are rare. We examined biopsies
      from three patients with cutaneous lesions of sinus histiocytosis, none of whom
      had detectable systemic involvement, and compared them to those of two patients
      whose lymph nodes were involved by the disease. The histology of skin lesions in
      all five cases showed dense nodular or diffuse infiltrates of "histiocytes,"
      emperipolesis of lymphocytes, neutrophils, and plasma cells. "Histiocytes" were
      present in lumens of dilated lymphatics. At the peripheries of the lesions were
      lymphoid aggregates and thick-walled vessels surrounded by plasma cells. Staining
      with anti-S-100 protein antibody showed marked cytoplasmic positivity in the
      "histiocytes" in each case. The only features that differed among the two groups
      were the presence of pseudoepitheliomatous hyperplasia and infiltrates of
      eosinophils in one case in which the disease was limited to the skin. We believe
      that cutaneous sinus histiocytosis can be specifically diagnosed by skin biopsy.
      Because cutaneous sinus histiocytosis may be unfamiliar to general pathologists,
      dermatopathologists, and dermatologists, cases limited to the skin may be under
      recognized.

PMID- 1401345
TI  - L-tryptophan syndrome: histologic features of scleroderma-like skin changes.
AB  - The eosinophilia-myalgia syndrome (EMS) associated with the ingestion of L
      tryptophan (LT) containing products has recently been recognized in the United
      States. We report the histologic features of the cutaneous scleroderma-like
      changes in four patients. All of the patients met the Center for Disease Control
      criteria for EMS and had a history of LT ingestion. Skin biopsies showed
      increased dermal mucin and dermal sclerosis, with trapping of adnexal structures.
      There are clinical and histologic similarities between EMS, scleroderma, the
      toxic oil syndrome, and fasciitis with eosinophils.

PMID- 1401346
TI  - Unusual variants of pemphigoid: from pruritus to pemphigoid nodularis.
AB  - We report three patients with pemphigoid nodularis. Patients were females aged
      76, 71 and 50 years, and all had features of bullous pemphigoid together with
      prurigo-like lesions at some stage of their illness. In two cases, nodular
      lesions preceded the onset of blistering by some months. Blisters arose on normal
      skin and in one patients also at sites of prurigo lesions. Routine histology of
      bullous lesions revealed the presence of subepidermal blisters. Electron
      microscopy performed in two cases confirmed the level of split to be through the
      lamina lucida. Direct immunofluorescence in all cases was positive, with linear
      basement membrane zone deposition of IgG and C3. Circulating IgG anti-basement
      membrane antibody was also detected in all patients, and in two, immunoblotting
      revealed a single antigen of 220 kD.

PMID- 1401347
TI  - Intravascular lymphomatosis: report of an unusual case with T cell phenotype
      occurring in an adolescent male.
AB  - Intravascular lymphomatosis is a rare disorder which most often occurs in the
      elderly. The overwhelming majority of the cases studied immunophenotypically have
      expressed a B cell phenotype. We report an unusual case of T cell intravascular
      lymphomatosis occurring in an adolescent male.

PMID- 1401348
TI  - Pigmented malignant pilomatrixoma: report of a case and review of the literature.
AB  - An unusual variant of malignant pilomatrixoma displaying melanization of
      epithelial elements is described. Melanization is a rare event even in the benign
      form of this adnexal neoplasm. Previously reported cases of malignant
      pilomatrixoma are reviewed; none containing pigment have been previously reported
      to our knowledge. Possible etiologies for lack of pigment in most benign and
      malignant pilomatrixoma are discussed.

PMID- 1401349
TI  - Plate-like sebaceous hyperplasia overlying dermatofibroma.
AB  - Epidermal hyperplasia, sometimes with primitive hair follicle-like
      differentiation, is a characteristic finding overlying dermatofibroma. We here
      report plate-like sebaceous hyperplasia overlying a dermatofibroma. Such changes
      are interpreted as a result of inductive epithelial effect by the dermatofibroma
      on the overlying epidermis.

PMID- 1401350
TI  - Milking of cows in late pregnancy: milk production during this period and during
      the succeeding lactation.
AB  - Fifteen lactating cows were milked throughout pregnancy, and the effects on milk
      performance were studied during this period and during the succeeding lactation,
      relative to 11 conventionally managed cows (2 months dry before calving) as
      controls. During the last 2 months of pregnancy, only nine cows did not dry off
      spontaneously. Protein and fat concentrations in milk increased rapidly, but the
      concentration of lactose, corrected for milk yield, did not change. The ratios of
      individual caseins to total protein decreased with the quantity of milk produced,
      but only for yields below approximately 6 kg/d. The relative proportion of kappa
      casein tended to decrease in the last milkings. During the succeeding lactation
      (first 15 weeks after calving and first 6 weeks of grazing) continuously milked
      cows yielded 4 kg milk/d less than the cows of the other group. The protein
      content of their milk was higher (2-3 g/kg depending on the period) than that of
      the control group, and the lactose content tended (P less than 0.10) to be lower.
      Changes in the relative proportions of nitrogenous fractions with time were not
      different in the two groups. Differences between the two groups in the
      concentration of protein in milk, and in the concentration of glucose and non
      esterified fatty acids in the plasma, suggest a better energy balance for the
      continuously milked cows during the succeeding lactation.

PMID- 1401351
TI  - Machine-induced teat tissue reactions and infection risk in a dairy herd free
      from contagious mastitis pathogens.
AB  - Machine-induced changes in teat thickness were measured in a randomly selected
      group of 22 cows from a commercial dairy herd consisting of 110 cows during an
      experiment lasting 1 year. Half the cows used were free from mastitis whereas the
      remainder had at least one quarter infected by environmental pathogens. Teats
      were classified according to a threshold change in teat end thickness of 5%. The
      relationships between quarter infection or teat duct colonization and teat end
      thickness changes induced by machine milking were investigated. Teats with
      greater than 5% change in thickness had significantly increased teat duct
      colonization and a slight, non-significant, increase in quarter infection. We
      conclude that machine-induced changes in teat end thickness are predisposing
      factors for teat duct colonization by environmental pathogens. This may provide
      an increased new infection risk, especially when hygiene is poor.

PMID- 1401352
TI  - Collection of fore and hind milk from the sow and the changes in milk composition
      during suckling.
AB  - A new sampling method for the collection of fore and hind milk from the sow has
      been developed which resembles normal milk removal by the piglet, yet overcomes
      the difficulties of collecting milk that is available for only a short time (10
      20 s) at each let-down. Samples of hind milk were collected immediately after the
      completion of a successful sucking, while the fore milk was collected at the
      beginning of the next natural let-down. Modification of existing assays for fat,
      protein and lactose was required to provide rapid analysis of the small volumes
      (less than 0.5 ml) of milk collected using this procedure, and these methods were
      validated by comparison with reference methods. Total solids and the
      concentration of fat in whole milk, and protein and lactose in skim milk, were
      measured in fore and hind milk collected from 4, 20, 12 and 12 sows respectively,
      6-11 d post partum. For fore milk, the results (mean +/- SD (n)) were: total
      solids, 199.9 +/- 9.9 g/l (8); fat, 96.7 +/- 13.9 g/l (41), protein, 47.7 +/- 4.5
      g/l (27) and lactose, 58.3 +/- 4.0 g/l (27). In hind milk, there was a
      significant increase in the concentration of fat (15.3 g/l, P less than 0.001, n
      = 41) which was reflected by a significant increase in total solids (14.7 g/l, P
      less than 0.001, n = 8) and calculated energy (511 kJ/l, P less than 0.001, n =
      27), but there was no significant difference in the concentration of either
      protein or lactose. This increase in milk fat during milk let-down is in contrast
      to the results of most previous studies in the sow and is discussed in terms of
      the possible mechanisms that may cause the concentration of fat to increase as
      milk is removed from the mammary gland.

PMID- 1401353
TI  - New alpha s2-casein variant from caprine milk.
AB  - A new alpha s2-casein variant was isolated from goat milk by means of covalent
      chromatography. With gel electrophoresis at alkaline pH, the alpha s2-casein
      variant showed a double band with the highest anodic mobility amongst the casein
      components. The mobility of the isolated alpha s2-casein variant was similar to
      that occurring in three individual samples of whole casein. Two dimensional
      electrophoresis revealed a more pronounced heterogeneity of this protein.
      Developing the two dimensional plate with polyclonal antibodies obtained against
      the four main bovine casein fractions, we demonstrated that the variant in
      question belongs to the alpha s2-casein family. Since the alpha s2-casein
      fractions, immunospecifically developed, spread along two different zones on the
      gel, it was concluded that a heterozygous alpha s2-casein form was present in the
      sample.

PMID- 1401354
TI  - Changes in structure of the bovine milk fat globule membrane on heating whole
      milk.
AB  - The effects of heat-induced interactions between milk fat globule membrane
      components and skim milk proteins in whole milk on the structure of the membrane
      were examined by isopycnic sucrose density gradient centrifugation and by using
      Triton X-100 as a membrane probe. Skim milk components were incorporated into all
      the lipoprotein fractions separated by density gradient centrifugation. High
      density complexes, higher in density than those found in the natural milk fat
      globule membrane, were formed during the heat treatment. Losses of natural
      membrane polypeptides from the medium and low density lipoproteins were observed
      on heating. Heating whole milk also altered the rate of release of membrane
      components by detergent, with decreases in protein released and an increase in
      phospholipid constituents released. Studies on washed cream indicated that some
      of the changes in the membrane on heating whole milk occurred due to the heat
      treatment alone, independent of the interactions with skim milk proteins.

PMID- 1401355
TI  - Effect of calcium on the stability of mares' milk lysozyme.
AB  - The three aspartic acid residues that form part of the Ca-binding site of mares'
      milk lysozyme have apparent pK values of 4.9, 4.3 and 4.1. The fluorescence of
      tryptophan has been used to compare the denaturation of mares' milk lysozyme by
      guanidinium chloride at various concentrations of Ca with that of hens' egg-white
      lysozyme (EC 3.2.1.17) and alpha-lactalbumin. Fluorescence revealed an
      intermediate stage in the denaturation of mares' milk lysozyme. The Ca-free form
      of mares' milk lysozyme is slightly more stable than that of alpha-lactalbumin,
      but its interaction with Ca is similar to that of alpha-lactalbumin, since only
      the native state binds Ca. Three-state models of denaturation can usefully be
      displayed on a ternary diagram.

PMID- 1401356
TI  - K+ and Cl- transport by mammary secretory cell apical membrane vesicles isolated
      from milk.
AB  - The transport of K+ (Rb+) and Cl- by membrane vesicles isolated from bovine milk
      has been studied using ion-exchange column chromatography. K+ (Rb+) and Cl-
      accumulation by the vesicles was time-dependent and was almost abolished by 0.1%
      Triton X-100, suggesting that uptake represents 'real' transport rather than
      binding. K+ (Rb+) uptake was influenced by the anion in solution in a manner
      suggesting that influx is sensitive to changes in vesicle membrane potential.
      Similarly, Cl- uptake was found to be sensitive to vesicle electrical potential:
      Cl- influx was enhanced by inside positive potentials. Cl- uptake was not
      saturable with respect to external Cl-. The results suggest that K+ (Rb+) and Cl-
      cross the apical membrane by way of conductance pathways. The similarity between
      ion transport by skim milk membrane vesicles and that of the apical aspect of the
      intact mammary epithelium suggests that the former may be a good model to study
      solute transport by the apical membrane of mammary secretory cells.

PMID- 1401357
TI  - Intracellular pH and the role of D-lactate dehydrogenase in the production of
      metabolic end products by Leuconostoc lactis.
AB  - The kinetics of lactate dehydrogenase from Leuconostoc lactis NCW1 were studied.
      The pH optimum for the enzyme depended on the concentration of pyruvate used in
      the assay and the enzyme displayed an ordered mechanism with respect to substrate
      binding. The Km for pyruvate and NADH and the Vmax of the enzyme decreased 20-,
      30- and 6-fold respectively as the pH decreased from 8.0 to 5.0. No activators
      were found and none of the intermediates of the phosphoketolase pathway tested
      inhibited the enzyme. ATP, ADP, GTP and NAD+ were inhibitory. The intracellular
      volume (Vol(in)) and intracellular pH (pH(in)) decreased as the extracellular pH
      (pH(ex)) decreased. Co-metabolism of citrate and glucose affected the Vol(in) but
      did not affect the pH(in), which decreased by 0.6 units per unit change in
      pH(ex); at pH 7.0, the pH(in) and pH(ex) were equal. The results suggest that
      pH(in) may play a role in determining the production of diacetyl and acetoin at
      low pH by Leuconostoc.

PMID- 1401358
TI  - Factors in ruminant colostrum that influence cell growth and murine IgE antibody
      responses.
AB  - Bovine colostrum was investigated as a source of biologically active molecules
      capable of stimulating the growth of mammalian cells in culture and modifying the
      immune response in a murine model. An extract prepared from bovine colostral whey
      by cation exchange and reversed-phase chromatography stimulated the growth of L6
      rat myoblasts, Balb/c-3T3 mouse fibroblasts and BHK-21 baby hamster kidney cells
      with equal or greater potency than fetal bovine serum. Fractionation of the
      bovine colostral extract by gel-permeation chromatography in M-acetic acid
      identified a number of cell-growth factors for each cell type. Bovine colostral
      extract was compared with an ovine colostral whey preparation for its ability to
      modulate IgE antibody responses in mice. Doses of 8 and 4 mg/d of ovine colostral
      whey or bovine colostral extract specifically suppressed IgE antibody responses,
      whereas at lower doses suppression did not occur. We conclude that bovine
      colostrum contains cell-growth factors as well as immunomodulatory factors that
      are able to regulate the IgE response in a heterologous species.

PMID- 1401359
TI  - Adherence of psychrotrophic bacteria to dairy equipment surfaces.
AB  - Psychrotrophic bacteria isolated from raw milk were tested for their ability to
      adhere to steel, two types of rubber, and glass, materials employed in the
      construction of milking equipment. The adherence assays were carried out by
      exposure of the materials to radioactively labelled bacteria in both a buffering
      solution (Ringer's) and milk. The degree of adherence of Gram-positive bacteria
      was lower (P less than 0.001) than that of Gram-negative bacteria. Glass was the
      material least prone to bacterial adherence (P less than 0.001); there were no
      significant differences between the other three materials. Milk was found to
      inhibit adhesion significantly (P less than 0.05), this inhibition being more
      evident with the most adherent bacteria. There was no statistically significant
      correlation between bacterial surface hydrophobicity and adherence. Our results
      suggest that intrinsic bacterial adherence cannot be considered a relevant factor
      in the contamination of milking equipment.

PMID- 1401360
TI  - Identification of a new molecular form of human alpha-lactalbumin.

PMID- 1401361
TI  - Comparison between the EC plate count test at 21 degrees C and an accelerated
      plate count method for assessing the keeping quality of pasteurized milk.

PMID- 1401362
TI  - Nutritional factors influencing the nitrogen composition of bovine milk: a
      review.

PMID- 1401363
TI  - Gas chromatographic analysis of volatile sulfur compounds from heated milk using
      static headspace sampling.
AB  - An investigation was conducted to test the feasibility of using gas
      chromatography with static headspace sampling as an objective tool to measure
      milk flavor quality. Heated milk off-flavor was chosen for study. Different
      strategies were tried for increasing the sensitivity of a commercially available
      headspace method, including salting out with sodium sulfate, cryofocusing during
      injection, and applying backpressure to the sampling loop. With the aid of a
      sulfur-specific detector, the resulting system was sufficiently sensitive to
      detect the sulfur volatiles, H2S and dimethyl sulfide, at the concentrations
      found in pasteurized skim milk. Milk that was heated to varying degrees was
      analyzed, and the analytical results were compared with the intensity of heated
      flavor as determined by a sensory panel. For skim milk, correlations were
      moderately strong: Spearman's correlation coefficients for H2S and dimethyl
      sulfide were .75 and .60, respectively. Correlations were weak for whole milk.

PMID- 1401364
TI  - The effect of day of the estrous cycle, location of ovulatory structure, and
      progesterone on in vitro bovine endometrial secretions.
AB  - Endometrial tissue was collected by biopsy from mature Holstein cows either on d
      0 (estrus) or on d 9, 14, or 18 of the estrous cycle to determine the effects of
      day of the cycle, uterine horn, and in vitro progesterone on endometrial protein
      secretion. Tissue was incubated for 24 h in supplemented media containing 14C
      amino acids and either 0, 4.7, or 47 ng of progesterone/ml. Media were analyzed
      for total protein, radiolabeled protein, and profile of protein released during
      incubation. Endometrial tissue at d 0 released more protein than did tissue
      collected on all other days. Radiolabeled proteins were greater on d 0 and 18
      than on d 9 and 14. Endometrium from the uterine horn contralateral to the corpus
      luteum released more radiolabeled protein than endometrium from the uterine horn
      ipsilateral to the corpus luteum. Seventeen protein bands were identified by
      electrophoresis. Proximity of the uterine horn to the site of ovulation affected
      the distribution of specific bands 21,400, 55,000, 74,600, and 88,100 molecular
      weight. The proportion of released proteins represented by proteins of molecular
      weights 12,700, 19,100, 21,400, 32,000, and 66,500 was affected either by day of
      the estrous cycle, proximity of uterine horn to the site of ovulation, or
      progesterone concentration. The results show that day of the estrous cycle and
      uterine horn not only alter overall endometrial protein secretion and synthetic
      activity but also have specific effects on distribution of individual proteins.

PMID- 1401365
TI  - Effect of interferon-gamma on the production of tumor necrosis factor during
      acute Escherichia coli mastitis.
AB  - The effects of recombinant interferon-gamma on the production of tumor necrosis
      factor in 10 dairy cows with Escherichia coli mastitis were determined.
      Prophylactic administration of recombinant interferon-gamma prior to the
      experimental E. coli challenge was effective in modifying the production of
      endogenous tumor necrosis factor during acute stages of disease. Elevated tumor
      necrosis factor concentrations were especially evident in cows that developed
      severe clinical symptoms and eventually died from endotoxemia. These results
      indicate that both milk and sera tumor necrosis factor concentrations are
      associated closely with the manifestation of peracute signs of coliform mastitis
      and are important factors contributing to morbidity and mortality of endotoxic
      shock. Pretreatment of cows with recombinant interferon-gamma possibly may down
      regulate the generation of this potent endogenous inflammatory mediator within
      infected quarters. Controlling severe inflammation with recombinant interferon
      gamma may prevent the tremendous loss in milk production and death that often
      accompany acute coliform mastitis during the periparturient period.

PMID- 1401366
TI  - Interactions between gluconeogenesis and fatty acid oxidation in isolated sheep
      hepatocytes.
AB  - The interaction of gluconeogenesis and fatty acid oxidation in isolated sheep
      hepatocytes was studied. Addition of tetradecylglycidic acid, an inhibitor of
      carnitine palmitoyltransferase I (EC 2.3.1.21), to isolated hepatocytes inhibited
      gluconeogenesis from a mixture of pyruvate plus lactate and from propionate
      alone. Inhibition constants for tetradecylglycidic acid on gluconeogenesis were
      4.77 +/- 1.00 microM and 7.25 +/- 1.52 microM, respectively, for pyruvate plus
      lactate and for propionate as gluconeogenic substrates. The inhibition constants
      were not different. At the highest substrate concentrations examined,
      gluconeogenesis from pyruvate plus lactate and from propionate in the presence of
      10 microM tetradecylglycidic acid was 47.3 and 41.4% of their respective
      controls. Similar to previous observations with butyrate, caproate addition
      inhibited gluconeogenesis from propionate by isolated hepatocytes and was unable
      to prevent inhibition of gluconeogenesis induced by tetradecylglycidic acid.
      Carnitine palmitoyltransferase I activity was lower in mitochondria isolated from
      hepatocytes preincubated with insulin than in control hepatocytes. The data
      suggest 1) that maximum rates of gluconeogenesis in isolated sheep hepatocytes
      from either pyruvate plus lactate or from propionate as gluconeogenic substrates
      require beta-oxidation, 2) that intermediates common to the metabolism of
      butyrate and caproate may be involved in the inhibition of propionate conversion
      to glucose by isolated sheep hepatocytes, and 3) that carnitine
      palmitoyltransferase I activity in isolated sheep hepatocytes can be modulated by
      insulin treatment.

PMID- 1401367
TI  - Milk yield, health, and reproduction of dairy cows given somatotropin
      (Somavubove) beginning early postpartum.
AB  - Cows (n = 210) were assigned to the following treatments: uninjected controls
      through 130 d postpartum; zero to high, uninjected through 60 d then injected
      with 14 mg of bST/d from 61 through 130 d postpartum; low, 5 mg of bST/d from 14
      through 130 d postpartum; low to high, 5 mg of bST/d from 14 through 60 d then 14
      mg of BST/d from 61 through 130 d postpartum; and high, 14 mg of bST/d from 14
      through 130 d postpartum. Cows given 5 mg of bST/d (low and low to high
      treatments) yielded 1.2 kg of FCM/d more and high group cows yielded 1.3 kg of
      FCM/d more than control cows between 14 and 60 d postpartum. Cows given bST
      yielded 2.7 to 4.1 kg of FCM/d more than control cows during 61 to 130 d
      postpartum. Overall, control cows yielded 35.1 kg of FCM/d, and bST-dosed cows
      yielded 2.2 to 3.2 kg/d more FCM. Low group cows had improved pregnancy rate
      (80.0%) and conception rate (82.2%) compared with high group cows (57.2 and
      60.3%). Neither pregnancy (70.0%) nor conception rates (71.5%) of controls
      differed from other groups. However, low group cows had first service conception
      rate of 57.8% compared with 34.3% for high and 38.2% for low to high group cows.
      First postpartum estrus was observed in high group cows about 13 to 16 d later
      than in low and low to high group cows, whereas low group cows came into first
      estrus 9 d sooner than controls. Cows of high group had lower body condition than
      controls (2.5 vs. 2.9), but other groups did not differ (2.7 to 2.9) from
      controls. Health was not adversely affected. Early postpartum bST administration
      at 5 mg/d increases FCM and, perhaps, reproductive performance of dairy cattle
      compared with herdmates.

PMID- 1401368
TI  - Methane prediction in dry and lactating Holstein cows.
AB  - Data from six experiments (two with dry cows) were used to predict partitioning
      of gross energy to CH4 in Holstein cows using selected independent variables,
      some of which were intercorrelated, and a stepwise backward elimination
      regression procedure. Methane outputs ranged from 3.1 to 8.3% (mean 5.5) of gross
      energy intake for 134 dry cow balance trials and from 1.7 to 14.9% (mean 5.2) of
      gross energy intake for 358 lactating cow energy balance trials. This is
      equivalent to 176 and 300 g/d or 245 and 419 L/d of CH4 for dry and lactating
      Holstein cows, respectively. Digestibilites of hemicellulose and neutral
      detergent solubles were positive predictors, and cellulose digestibility was a
      negative predictor of CH4 output in dry cows fed all forage diets, but
      hemicellulose digestibility was not a significant variable for predicting CH4
      production by lactating cows fed diets with concentrate and forages. Fiber
      digestibility generally remained in models to predict CH4 output. Except for one
      data set, regression equations accounted for 50 to 72% of the variation in
      percentage of gross energy partitioned to CH4 by Holstein cows. Results confirm
      that increased concentrate feeding reduces CH4 production. Supplementation of
      lactation diets with fat generally increases fat digestibility, and this trait
      was associated with reduced CH4 output. Results enable 1) estimation of CH4
      output for calculation of metabolizable energy and 2) computation of the
      contribution from dairy cows to global warming.

PMID- 1401369
TI  - Determination of markers in digesta and feces by direct current plasma emission
      spectroscopy.
AB  - A method is described for the preparation of bovine ruminal contents, duodenal
      digesta, and feces for analysis of Co, Cr, La, Sm, Eu, and Yb by direct current
      plasma emission spectroscopy. Ground, dried sample was refluxed in concentrated
      nitric acid until 2 to 3 ml of acid remained. The ash was redissolved in 6N HCl.
      Lithium hydroxide was added to suppress ionization, and the samples were diluted
      with distilled water for analysis. Element recovery, expressed as the ratio of
      element recovered from digesta samples augmented prior to ashing compared with
      those augmented after sample digestion, ranged from 71.5 to 100.5% and was
      affected by digesta type. Addition of 1000 ppm of Li to the sample matrix
      improved recovery of Co and La from 93.4 and 83.3% to 97.8 and 98.3%,
      respectively. Lithium did not affect recovery of the other elements. Type of
      digesta matrix affected emission intensity. Addition of 1000 ppm of Li to the
      sample matrices enhanced signal output in the digesta matrices by 25 to 30% for
      each element. Lithium tended to minimize differences in signal output caused by
      the organic matrix but did not eliminate them. Increasing Li concentration from
      1000 to 4000 ppm did not increase signal output or completely buffer out the
      higher emission intensity associated with the organic matrix. Sensitivity of
      analysis of Co, Cr, and rare earth elements was comparable with or better than
      sensitivities reported with neutron activation analysis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1401370
TI  - Vitamin E effects on in vitro immunoglobulin M and interleukin-1 beta production
      and transcription in dairy cattle.
AB  - Experiments were conducted to determine the effect of dietary vitamin E on in
      vitro IgM and interleukin-1 production and its transcription by bovine peripheral
      blood mononuclear cells. Cells were isolated from Jersey cows and cultured with
      pokeweed mitogen, a T-cell-dependent, B-lymphocyte mitogen, to stimulate
      polyclonal IgM production. Addition of 55 and 110 ng/ml of alpha-tocopherol at
      time 0 to cell cultures containing pokeweed mitogen significantly enhanced IgM
      production compared with control cultures containing pokeweed mitogen alone.
      Cultures supplemented with 55 ng/ml of alpha-tocopherol at 0, 24, or 48 h after
      incubation with mitogen had enhanced IgM production compared with control
      cultures incubated for the same duration. However, addition of alpha-tocopherol
      to cultures at 72 and 96 h did not affect IgM production. Production of
      interleukin-1 in culture supernatants obtained 24 h after stimulation with
      pokeweed mitogen was similar between control cultures and cultures supplemented
      with alpha-tocopherol. At 48 h, secretion of interleukin-1 was maintained in the
      supplemented cultures but declined in control cultures. Mononuclear cells
      obtained from steers receiving vitamin E supplement or control steers were used
      to examine the effects of in vivo vitamin E status on interleukin-1 mRNA
      expression. Concanavalin A-stimulated cells from Jersey steers fed diets
      supplemented with vitamin E expressed 55% higher interleukin-1 mRNA than cells
      from control steers.

PMID- 1401371
TI  - Stimulation of luteal cell progesterone production by lipoproteins from cows fed
      control or fat-supplemented diets.
AB  - Plasma lipoproteins from lactating dairy cows fed 0 or 7% supplemental fat were
      examined for their composition and ability to stimulate luteal cell progesterone
      production in vitro. Ultracentrifugation was utilized to isolate blood
      lipoproteins, and heparin affinity chromatography allowed separation of
      lipoprotein fractions based on the presence (low density lipoproteins) or absence
      of apolipoprotein B (high density lipoproteins). A portion of high density
      lipoproteins was fractionated by size, utilizing gel filtration chromatography.
      Slaughterhouse corpora lutea were dissociated, and plasma lipoproteins were added
      to the luteal cells on d 3 of culture and incubated for 48 h. In Experiment 1,
      blood was collected from heifers fed a diet that was not supplemented with fat.
      The addition of cholesterol from large, high density lipoproteins with a high
      cholesterol to protein ratio to luteal cultures increased progesterone production
      by an average of 17% compared with the addition of cholesterol from small, high
      density lipoproteins with a low cholesterol to protein ratio. In Experiment 2,
      electrophoretic mobility, apolipoprotein composition, and size of lipoproteins
      from control and fat-supplemented cows were similar. Lipoproteins from cows
      assigned to either a control or fat-supplemented diet showed no difference in
      their ability to stimulate progesterone production. Increased plasma progesterone
      concentration in lactating dairy cows fed supplemental fat does not appear to be
      mediated by alterations in lipoprotein composition.

PMID- 1401372
TI  - Protein digestion and intestinal amino acids in dairy cows fed fresh Lolium
      perenne with different nitrogen contents.
AB  - An experiment was carried out to study digestion and intestinal AA in three
      ruminally and duodenally cannulated, lactating cows fed freshly cut grass (Lolium
      perenne) fertilized with 500 and 275 kg of N/ha per yr, respectively. High N
      grass was fed in June and October, and low N grass was offered in July and
      September. Composite samples of the grass fed in each period also were tested for
      in situ degradation of OM, CP, and NDF. When low N grass was fed, the
      digestibilities of OM and CP were lower than when high N grass was fed. On low N
      grass, the duodenal N flow expressed per unit of N intake was higher, although
      the flow of AA N on low N grass was reduced in September, mainly because of
      reduced microbial protein synthesis from slower OM degradation of low N grass.
      Duodenal N flow per unit of N intake was related negatively to the N:OM ratio of
      the diet. The rate of N fertilization had no effect on ruminal OM and NDF
      turnover rates. Turnover and passage rates in this experiment were not different
      from reported data on cows on winter rations with similar DMI.

PMID- 1401373
TI  - Influence of bovine somatotropin on the composition and manufacturing properties
      of milk.
AB  - Three studies (84, 140, and 200 d) were performed to examine the effect of
      injecting dairy cows with various doses (0, 320, 640, or 960 mg/28 d; 0 or 640
      mg/28 d; 0, 320 mg/14 d, or 320 or 640 mg/28 d) of bST on milk production,
      composition, and manufacturing properties. Mean bST response among studies on
      milk production varied from 0 (trial 1) to 7.3% (trial 2) and from 8.5 to 14.2%
      (trial 3) in relation to feeding conditions. Neither milk fat nor protein
      percentages in milk at time of maximum response were affected by the use of bST.
      Distribution of casein and protein in the whey was not affected by the treatments
      at any time. The nature of fatty acids varied more with time after injection than
      with bST doses. Neither coagulation time, standard curd firmness, nor soft or
      pressed cheese yields were affected by the treatments.

PMID- 1401374
TI  - Effects of lasalocid on selected ruminal and blood metabolites in young calves.
AB  - Twelve Holstein bull calves were ruminally cannulated at 5 d of age and assigned
      to 0 or 1 mg of lasalocid/kg of BW daily, administered postruminally via milk
      replacer or into the ruminal cannula. Calves were fed milk replacer for 8 wk and
      calf starter for 12 wk. Lasalocid administration was terminated at weaning in
      calves fed lasalocid in milk replacer. Ruminal pH tended to be higher in calves
      fed lasalocid ruminally than in calves on control treatment and averaged 5.9 and
      5.6 and 5.4 and 5.1 during wk 1 to 8 and 9 to 12, respectively. Molar proportion
      of ruminal butyrate tended to be lower when lasalocid was added to the rumen,
      particularly after weaning. Blood beta-hydroxybutyrate and acetoacetate were
      lower when lasalocid was administered into the rumen after weaning and averaged
      .897 and .646 and .026 and .015 mM in calves on control and ruminal treatments,
      respectively. No effects of lasalocid administered via the milk replacer were
      observed, except for plasma NEFA, which were reduced postweaning. These data
      suggest that lasalocid reduces blood beta-hydroxybutyrate by changes in ruminal
      fermentation and subsequent metabolism of butyrate by ruminal epithelium.

PMID- 1401375
TI  - Estimates of genetic trend in an artificial insemination progeny test program and
      their association with herd characteristics.
AB  - Individual lactation records from Holstein cows in 3449 herds participating in an
      AI stud's young sire sampling program from 1971 to 1987 were used to characterize
      the sampling program and to estimate genetic merit and trend. Average genetic
      merit of cows in sampling program herds was consistently superior to the average
      genetic merit of cows in the US population. Genetic trend of sires of first-crop
      cows was 58 kg of milk and 1.5 kg of fat/yr from 1971 to 1978 and 176 kg of milk
      and 5.5 kg of fat/yr from 1979 to 1987. The average genetic merit of sires of
      first-crop cows born after 1983 was equivalent to or exceeded the genetic level
      of sires of other cows in the herd. Within-herd-year means and standard
      deviations of yield, genetic evaluation, and management traits (herd-year
      characteristics) were computed for a subset of 341 herds contributing first-crop
      daughters for at least 10 yr. The average of each herd-year characteristic during
      10 or more years was used to predict within-herd genetic trend. Herd
      characteristics explained up to 51% of differences in within-herd genetic trends.
      Average sire genetic merit of daughters other than first-crop daughters accounted
      for up to 80% of the explained differences. Other herd characteristics suggested
      that herds with larger within-herd standard deviation milk yields, a larger
      number of young sires represented, younger cows, and greater percentage of cows
      sired by AI sires made greater genetic improvement. Results indicated that the
      average genetic merit of cows and the rate of within-herd genetic improvement are
      higher in herds that participate in a young sire sampling program.

PMID- 1401376
TI  - Estimation of genetic parameters for somatic cell score in Holsteins.
AB  - Genetic parameters of somatic cell scores for Holstein cows were estimated using
      an animal model and REML for two data sets. Set 1, with 13,017 records from 5278
      cows, was used to obtain variance components, heritability, and repeatability for
      two lactation measures: the simple average and the weighted average of test day
      data. Set 2, with 14,418 records from 4806 cows, was used to obtain genetic
      correlations for the simple average between lactations 1 and 2, between
      lactations 1 and 3, and between lactations 2 and 3. Simple and weighted average
      of test day somatic cell scores had the same heritabilities (.12) and
      repeatabilities (.35). Phenotypic variances were about 1.2, and herd-sire
      interaction variances were small (.002). Genetic correlation for somatic cell
      score was about .55 between lactations 1 and 2 and between lactations 1 and 3 and
      .65 between lactations 2 and 3. Phenotypic correlation was .20 between lactations
      1 and 2, .16 between lactations 1 and 3, and .31 between lactations 2 and 3.

PMID- 1401377
TI  - Genetic correlations between lifetime production and linearized type in Canadian
      Holsteins.
AB  - Genetic and phenotypic correlations were estimated between 6 lifetime production
      and 28 linearized type traits using REML. The data set contained 34,322 cows,
      each with a record for all 34 traits. The analyses accounted for the fixed
      effects of herd, year-month, classifier, age at first calving, and stage of
      lactation. Heritabilities were low for lifetime traits and moderate for most type
      traits except stature, size, capacity, thurl width, and pin setting, which had
      high heritabilities. Most phenotypic correlations between lifetime production and
      type were in the range of .15 to .20 except for capacity, rump, and feet and
      legs, which were around .07. Genetic correlations were strong between lifetime
      production and angularity (.44 to .55) and dairy character (.53 to .56). Genetic
      correlations were low to moderate between life-time production and stature (.14
      to .25), size (.07 to .18), texture (.19 to .26), style (.11 to .27), head (.15
      to .23), pin setting (.10 to .16), rear udder (.19 to .25), and rear attachment
      (.10 to .22). The only notable negative genetic correlations were lifetime
      production with rear heel (-.16 to -.27), thurl width (-.18 to -.24), and fore
      udder (-.05 to -.11).

PMID- 1401378
TI  - Estimation of residual energy intake for lactating cows using an animal model.
AB  - Residual energy intake is defined as the remaining energy from total net energy
      intake after accounting for all energy uses. Residual energy intake is proposed
      as a measure of feed efficiency because animal efficiency increases as the
      proportion of accountable energy intake increases or the residual energy intake
      decreases. Residual energy intake was estimated for each of 247 Holstein cows,
      daughters of 127 sires and 226 dams distributed in five herds across the US. Data
      consisted of daily milk production and net energy intake, biweekly measures of
      milk components, and BW measures taken at varied intervals throughout a
      lactation. Average daily net energy intake in a lactation was the dependent
      variable in a model that contained fixed effects of parity and herd-season
      subclass; covariates of lactation average daily SCM, metabolic BW, and weight
      change in a lactation; and random animal effect. From this model, residual energy
      intake was a sum of animal and residual effects. Partial energy requirements for
      SCM, maintenance, and weight change estimated for all cows were .54, .15, and
      1.52 Mcal/kg, respectively. Heritability estimate for residual energy intake was
      .016; phenotypic standard deviation was 2.455. The proportion of the phenotypic
      standard deviation in net energy intake that was due to residual energy was 68%.

PMID- 1401379
TI  - Designing animals: ethical issues for genetic engineers.
AB  - Two general philosophical approaches to ethical issues in property rights are
      described. Instrumental approaches take property rights to be means for achieving
      goals such as social efficiency or economic growth. Labor approaches take
      property rights to be fundamental human rights that protect liberty or that
      assign ownership of goods based on criteria of desert. A thought experiment is
      used to illustrate the relevance of these theories to intellectual property.
      Alternative strategies for application of ethical theory to animal biotechnology
      are surveyed. The choice of an approach determines a burden of proof that must be
      met before property claims can be ethically sanctioned, but the question of which
      approach should be applied to animal biotechnology remains open. Ethical issues
      raised by unwanted consequences of biotechnology and religious objections to gene
      transfer are briefly summarized with emphasis on how these issues have influenced
      public debate on animal patents.

PMID- 1401381
TI  - The effects of psychotherapy: an evaluation. 1952.

PMID- 1401380
TI  - Microbial protein synthesis and flows of nitrogen fractions to the duodenum of
      dairy cows.
AB  - Attempts have been made to increase nutrient availability for milk production by
      increasing feed intake, optimizing ruminal fermentation, and supplementing
      nutrients to the diet that will escape ruminal degradation. Energy and N are the
      nutritional factors that most often limit microbial growth and milk production.
      Ruminal fermentation and flow of microbial and dietary protein to the small
      intestine are affected by feed intake and by the amount and source of energy and
      protein in the diet. Feeding protein and carbohydrate that are not degraded in
      the rumen increases the quantity of dietary protein that passes to the small
      intestine but may decrease the quantity of microbial protein that is synthesized
      in the rumen. This often results in only small differences in the total NAN that
      passes to the small intestine. Because microbial protein supplies a large
      quantity of total AA that passes to the small intestine, differences in passage
      of individual AA often are only slight. Additional research with cows consuming
      large amounts of feed are needed to identify combinations of feed ingredients
      that synchronize availabilities of energy and N for optimizing ruminal digestion,
      microbial protein synthesis, nutrient flow to the small intestine, and milk
      production and composition.

PMID- 1401382
TI  - A meta-analysis of antidepressant outcome under "blinder" conditions.
AB  - A meta-analysis of 22 studies of antidepressant outcome assessed the level of
      medication effects under conditions thought to be less subject to clinician bias
      than those in the typical double-blind drug trial. Studies were included only if,
      in addition to a newer antidepressant group, they also contained both standard
      antidepressant and placebo control groups. Effect sizes were quite modest and
      approximately one half to one quarter the size of those previously reported under
      more transparent conditions. Effect sizes that were based on clinician outcome
      ratings were significantly larger than those that were based on patient ratings.
      Patient ratings revealed no advantage for antidepressants beyond the placebo
      effect. Effect sizes were unrelated to sample sex ratios, patient age, inpatient
      or outpatient status, dosage level, and treatment duration. Findings highlight
      the fragility of the antidepressant effect.

PMID- 1401383
TI  - Taking context seriously in psychotherapy research: relating therapist
      interventions to patient progress in brief psychodynamic therapy.
AB  - This study examined the process of brief psychodynamic therapy in a way that
      preserved the context of the dialogue between therapist and patient. Data were
      drawn from transcripts of the complete therapies of 2 anxious and depressed
      women, which lasted 16 to 17 sessions. Patient utterances were rated on a
      psychodynamically oriented progress-stagnation scale, and all therapist
      interventions were rated on scales measuring (a) their compatibility with the
      content of a psychodynamic formulation (Plan) and (b) their quality. Within
      session sequential analyses and by session and by phase-of-therapy correlational
      analyses were performed. Plan compatibility of therapist interventions correlated
      significantly with patient progress in the early and middle phases, and the
      quality of therapist interventions correlated significantly with patient progress
      in the middle phase.

PMID- 1401384
TI  - Tobacco withdrawal in self-quitters.
AB  - Self-reported and observer-rated signs and symptoms of nicotine withdrawal were
      assessed precessation and 2, 7, 14, 30, 90, and 180 days postcessation in smokers
      who quit on their own for 30 days. Anxiety, difficulty concentrating, hunger,
      irritability, restlessness, and weight gain increased, and heart rate decreased,
      postcessation (p less than .001). Except for hunger and weight gain, these
      symptoms returned to precessation levels by 30 days postcessation. Craving,
      depression, and alcohol or caffeine intake did not reliably increase.
      Postcessation depression, but not withdrawal symptoms, craving, or weight gain,
      predicted relapse. These results are consistent with prior studies.

PMID- 1401385
TI  - Gender differences in the learning status of diabetic children.
AB  - The learning status of 95 diabetic boys and girls and 97 matched controls was
      evaluated using the Wechsler Intelligence Scale for Children--Revised IQ factors
      and school histories. Of interest was whether diabetic boys would evidence more
      learning difficulties. Results indicated that diabetic boys had significantly
      lower Freedom From Distractibility scores compared with scores of diabetic girls
      and control Ss and lower Perceptual Organization scores compared with scores of
      control boys. Although group scores were still within the average range of
      functioning, a significantly high percentage of diabetic boys (40%) compared with
      diabetic girls (16%) had learning problems that warranted either special
      instructional services or grade retention. Diabetic children experienced more
      learning difficulties (24%) than controls (13%), supporting research findings
      that diabetes is associated with increased risk of learning problems.

PMID- 1401387
TI  - Life stress and treatment course of recurrent depression: 1. Response during
      index episode.
AB  - Research on treatment course and outcome in depression is mixed with respect to
      the implications of life stress. Several concerns are addressed in a prospective
      study of 91 individuals treated for recurrent depression. Specific forms of
      stress occurring before treatment entry predicted a poor clinical response both
      after 16 weeks and after a more extended intervention period. Specific forms of
      stress occurring during the 1st 6 weeks of treatment also predicted poor response
      after 16 weeks and after the extended intervention period. Severe stress
      occurring early in treatment predicted a longer time to attain relief for
      treatment responders. Concepts underlying the idea that stress-related disorders
      have a better clinical outcome are discussed, and it is proposed that life stress
      has different implications for individuals with and without recurrent depression.

PMID- 1401386
TI  - Relationship between drug use and other problem behaviors in urban adolescents.
AB  - This study tested the generality of Jessor and Jessor's (1977) problem behavior
      theory, which states that a variety of problem behaviors constitute a behavioral
      syndrome in normal adolescents. Relationships among 5 adolescent problem
      behaviors (cigarette use, alcohol use, marijuana use, delinquency, and sexual
      intercourse) were examined in 7th-grade boys (n = 556) and girls (n = 715), and
      9th-grade boys (n = 481) and girls (n = 485) in an urban school system in which
      the majority of students were African American and from low-income families.
      Measures of problem behavior frequency were positively correlated with each other
      and negatively correlated with several measures of conventional behavior.
      Confirmatory factor analyses replicated findings of previous studies that a
      single common factor underlies adolescent problem behaviors.

PMID- 1401388
TI  - Perceptions of AIDS susceptibility among minority and nonminority women at risk
      for HIV infection.
AB  - Two hundred seventy-two women sampled from mass transit waiting areas in an urban
      center completed anonymous surveys of AIDS-related risk behavior, perceptions of
      susceptibility, and knowledge. Variable patterns of human immunodeficiency virus
      (HIV) risk behaviors were identified, with 22% of women reporting high-risk
      behavior. Perceptions of susceptibility were associated with an interaction
      between ethnicity and level of risk; nonminority women at high risk reported
      greater concern about AIDS than did minority women at high risk, who did not
      differ from women at low risk. With an array of life problems and inaccurate
      information about HIV transmission, minority women were found to be at continued
      risk for AIDS-related behavior. Implications for culturally sensitive and
      relevant AIDS prevention efforts are discussed.

PMID- 1401389
TI  - Cognitive problem-solving skills training and parent management training in the
      treatment of antisocial behavior in children.
AB  - This study evaluated the effects of problem-solving skills training (PSST) and
      parent management training (PMT) on children (N = 97, ages 7-13 years) referred
      for severe antisocial behavior. Children and families were assigned randomly to 1
      of 3 conditions: PSST, PMT, or PSST and PMT combined. It was predicted that (a)
      each treatment would improve child functioning (reduce overall deviance and
      aggressive, antisocial, and delinquent behavior, and increase prosocial
      competence); and (b) PSST and PMT combined would lead to more marked, pervasive,
      and durable changes in child functioning and greater changes in parent
      functioning (parental stress, depression, and overall symptoms). Expectations
      were supported by results at posttreatment and 1-year follow-up. PSST and PMT
      combined led to more marked changes in child and parent functioning and placed a
      greater proportion of youth within the range of nonclinic (normative) levels of
      functioning.

PMID- 1401390
TI  - Cognitive processing therapy for sexual assault victims.
AB  - Cognitive processing therapy (CPT) was developed to treat the symptoms of
      posttraumatic stress disorder (PTSD) in rape victims. CPT is based on an
      information processing theory of PTSD and includes education, exposure, and
      cognitive components. Nineteen sexual assault survivors received CPT, which
      consists of 12 weekly sessions in a group format. They were assessed at
      pretreatment, posttreatment, and 3- and 6-month follow-up. CPT subjects were
      compared with a 20-subject comparison sample, drawn from the same pool who waited
      for group therapy for at least 12 weeks. CPT subjects improved significantly from
      pre- to posttreatment on both PTSD and depression measures and maintained their
      improvement for 6 months. The comparison sample did not change from the pre- to
      the posttreatment assessment sessions.

PMID- 1401392
TI  - General deviance syndrome: expanded hierarchical evaluations at four ages from
      early adolescence to adulthood.
AB  - Problem behavior theory predicts that norm-violating attitudes and activities
      reflect a syndrome. Hierarchical latent-factor models examined the integrity of
      this syndrome at 4 developmental stages from early adolescence to adulthood.
      Latent constructs of Drug Use, Academic Orientation, Social Conformity, Criminal
      Behavior, and Sexual Involvement were assessed up to 4 times at 4-year intervals
      in a community sample. Second-order constructs of General Deviance confirmed
      integrity of the syndrome at these life stages, although subtle changes in
      certain components of the construct emerged. Criminal Behavior was more
      determined by General Deviance in adulthood than in young adulthood, whereas
      Sexual Involvement became less determined by the common factor between these
      times. Drug Use and low Social Conformity were consistently strong indicators of
      General Deviance.

PMID- 1401391
TI  - Preliminary typology designed for treatment matching of driving-while-intoxicated
      offenders.
AB  - A typology of 156 convicted driving-while-intoxicated (DWI) offenders was
      developed using cluster analysis and external validation procedures. The typology
      was derived from 4 variables (alcohol dependence severity, psychiatric severity,
      bad-driving index, and social instability) selected to maximize the feasibility
      of performing treatment matching with DWI offenders. Five clusters that suggested
      specific treatment matching opportunities were identified. The largest, Cluster 4
      (31% of cases), showed a low problem profile. However, a moderate-severity group
      (Cluster 1), a high-risk driver group (Cluster 2), and two high problem-severity
      groups (Clusters 3 and 5) were also found. Clusters 3 and 5 had high levels of
      alcohol dependence and psychiatric symptoms but differed significantly on social
      instability.

PMID- 1401393
TI  - Sequential analysis of chronic pain behaviors and spouse responses.
AB  - Social reinforcers such as spouse behaviors have been hypothesized to be
      important in maintaining chronic pain behavior. This study used direct
      observation to test whether solicitous and aggressive spouse behaviors
      systematically precede and follow patient pain behaviors. Fifty chronic pain
      patients and spouses and 33 control couples were videotaped performing specified
      tasks. Spouse solicitous behaviors were significantly more likely to precede and
      follow nonverbal pain behaviors, and nonverbal pain behaviors were significantly
      less likely to follow spouse aggressive behaviors in pain than in control
      couples. Within couples, spouse solicitous behaviors preceded and followed verbal
      and nonverbal pain behaviors beyond chance levels more often in pain than in
      control couples. Results support an operant conceptualization of factors
      maintaining chronic pain behaviors.

PMID- 1401395
TI  - Relationship between psychosocial functioning and body fat in preschool children:
      a longitudinal investigation.
AB  - This study examined whether preschool children differed on measures of
      psychosocial functioning both cross-sectionally and longitudinally. One hundred
      and thirty-two children who varied in levels of body fat participated in the
      study along with their natural parents. Results indicated that the children did
      not differ in levels of self-esteem and family functioning as a function of their
      body fat. Prospectively, physical self-esteem weakly (but significantly)
      correlated with body fat at 1 and 2 years, and father's perception of family
      functioning predicted body fat at 1 year only. Results suggested that childhood
      obesity may not develop as a result of psychosocial factors.

PMID- 1401394
TI  - Predicting early adolescent disorder from childhood aggression and peer
      rejection.
AB  - Two large cohorts of Black 3rd-grade children from low-income families were
      followed into early adolescence. Adjustment at the end of the 1st year of middle
      school was assessed by teacher and parent ratings and by adolescent self-reports.
      Childhood peer social status predicted parent-reported externalized and
      internalized disorder and self-reported internalized disorder. Childhood
      aggression predicted self-reported externalized and internalized disorder and
      parent-reported externalized disorder. Teacher ratings of school adjustment were
      predicted by aggression, rejection, and sex of the child. Consensus judgments of
      poor adjustment were predicted by both aggression and peer rejection, with sex
      moderating the effect of peer rejection. Both childhood aggression and peer
      rejection appear to be significant predictors of adolescent disorder, with each
      making a predictive contribution uniquely its own.

PMID- 1401396
TI  - Who will relapse? Symptoms of nicotine dependence predict long-term relapse after
      smoking cessation.
AB  - Results of a prospective examination (N = 618) of factors associated with smoking
      relapse are reported. At 1-year follow-up, a modified version of the Fagerstrom
      Tolerance Questionnaire (Dependence Index; DI) and a measure of craving entered
      the logistic model (odds ratio of 2.7 [p less than .001]). At Year 2, only the DI
      entered the model (odds ratio of 2.2 [p less than .001]). The ability of signal
      detection analysis (SDA) to produce clinically useful decision rules was also
      examined. At Year 1, SDA produced 1 subgroup with a 25% nonrelapse rate and
      another with a 9% nonrelapse rate (odds ratio of 3.4 [p less than .001]). At Year
      2, SDA produced 1 subgroup with a nonrelapse rate of 19% and another with a
      nonrelapse rate of 7% (odds ratio of 3.0 [p less than .001]). The use of signal
      detection methods may help clinicians to identify those at greater or lesser risk
      of relapse.

PMID- 1401397
TI  - Relative importance of informational units and their role in long-term recall by
      closed-head-injured patients and control groups.
AB  - The purpose of this study was to apply qualitative analysis to the information
      recalled by control Ss and closed-head-injured (CHI) patients. The Logical Memory
      subtest of the Wechsler Memory Scale (Wechsler, 1945) was administered to 40 CHI
      and 40 control Ss. Recall was tested immediately after administration, 40 min
      later, and 24 hr later. The analysis took into account the importance of recalled
      information as determined by a prior rating according to 3 levels of importance.
      Results suggest that CHI patients have difficulty selectively retrieving the most
      important information after a long delay.

PMID- 1401398
TI  - Panel attrition and external validity in adolescent substance use research.
AB  - Panel attrition threatens external validity in adolescent substance use research.
      A 7-year adolescent panel was examined to determine whether attrition effects
      varied by (a) type of substance assessed and (b) method of measurement and type
      of statistical analysis. Chi-squares and multivariate analyses of variance
      revealed that study dropouts were more likely to use substances and reported
      higher mean use of substances at baseline than stayers; attrition effects varied
      by substance; and mean use comparisons were more likely to detect attrition
      effects than use-nonuse comparisons. Implications of these findings for
      adolescent substance use research are discussed.

PMID- 1401399
TI  - Response of obese binge eaters to treatment by behavior therapy combined with
      very low calorie diet.
AB  - This study examined attrition and weight loss in 235 female obese binge eaters,
      episodic overeaters, and nonbingers treated by a 26-week program of behavior
      modification and very low calorie diet. No significant differences were observed
      among conditions in the number of Ss who completed treatment. Episodic
      overeaters, however, were more likely than Ss in the other 2 conditions to drop
      out during the last 7 weeks of treatment, when Ss resumed consumption of a
      conventional diet. End-of-treatment weight losses for the 3 conditions, which did
      not differ significantly, averaged 21.5, 19.4, and 21.7 kg, respectively. No
      significant differences were observed among conditions in weight regain (which
      averaged 8.8 kg) in the year following treatment, although small sample sizes
      prevented an adequate evaluation.

PMID- 1401400
TI  - Validity of phallometric measures with sex offenders: comments on the Quinsey,
      Laws, and Hall debate.
AB  - In a recent debate, Quinsey and Laws (1990) and Hall (1990) discussed several
      major methodological issues in research on the validity of phallometric tests.
      This article examines specific points of the debate more closely and uncovers
      questionable assumptions underlying some of the Quinsey and Laws criticisms. The
      implications of unresolved problems for the clinical use of phallometric measures
      are stressed.

PMID- 1401401
TI  - Children in crisis: nation in crisis.

PMID- 1401403
TI  - Evaluation of treatment times for Class II resin composite inlays.
AB  - Time registrations for indirect class II resin composite inlays are given. They
      are compared with treatment times for direct resin composite restorations.

PMID- 1401402
TI  - Bonding to dentin: evaluation of three adhesive materials.
AB  - Dye penetration was observed in all specimens. SEM demonstrated isolated areas
      with no gap formation, suggesting a partial bond with dentin. A correlation is
      evident from the results of both techniques. Since dye-penetration was found to
      be similar in all the specimens, it was difficult to assess the effect of
      thermocycling on the amount of dye penetration. The use of posterior composites
      should be considered as a short-term tested procedure. It should be utilized
      carefully, following the manufacturer's instructions, and monitored routinely.
      Undoubtedly, the utilization of posterior composite materials is a very technique
      sensitive procedure. Comparing the results of this in vitro study with those
      previously reported suggests that little improvement has been made in the bonding
      of the materials tested. Development of new materials and improved techniques are
      necessary.

PMID- 1401404
TI  - Mandibular movements and their relationship to age and body height in children
      with or without clinical signs of craniomandibular dysfunction: Part IV. A
      comparative study.

PMID- 1401405
TI  - Craniomandibular dysfunction in children: Part V. Correspondence between signs
      and symptoms.
AB  - Three hundred and fifty children, ages six to ten years, were examined and
      interviewed for clinical signs and symptoms of craniomandibular dysfunction. The
      subjects were classified by parents according to their emotional states.

PMID- 1401406
TI  - The prediction of eruption-sequence from panoramic radiographs.
AB  - The author tests the validity of predicting the eruption-sequence of permanent
      teeth from orthopantomograms taken during the early mixed dentition, based on
      criteria of root formation.

PMID- 1401407
TI  - Tooth eruption in failure-to-thrive infants.
AB  - The purpose of this study was to determine whether differences existed between
      the numbers of erupted teeth of infants who were failing to thrive and their
      controls. The results suggest a relationship does exist.

PMID- 1401408
TI  - Readiness for toothbrushing of young children.
AB  - The authors attempt to establish the types of guidance in toothbrushing suitable
      for young children. They examined the ability of preschool children to learn
      toothbrushing, and attempted to clarify the readiness of each age-group.

PMID- 1401409
TI  - The paradental cyst of the mandibular permanent first molar: report of a
      bilateral case.
AB  - A case of bilateral paradental cysts affecting the first permanent molars is
      described. Radiographic characteristics and differential interpretations of the
      lesion are discussed.

PMID- 1401410
TI  - Fusion of primary mandibular teeth: report of case.
AB  - The treatment and observation of a child with fused mandibular primary lateral
      incisor and canine are presented. Asymmetries such as those caused by fusions can
      lead to serious malocclusion.

PMID- 1401411
TI  - Differences in the health status of black and white children.

PMID- 1401412
TI  - Juvenile arrests--it's a crime.
AB  - Crime committed by children is on the increase. Dentists who treat children
      should be acquainted with the extent of criminal activities in which children in
      our cities, suburbs, and rural areas participate.

PMID- 1401413
TI  - Mexican-American parents with children at risk for baby bottle tooth decay: pilot
      study at a migrant farmworkers clinic.
AB  - Treatment of severe BBTD in very young children often requires the use of general
      anesthetic. In 1987, the cost was estimated at $700-$1,000; add another $1,000,
      if hospitalization is needed. Informal surveys of dentists across the country
      indicate that in 1991-1992, the cost of treatment has increased substantially.

PMID- 1401414
TI  - Prevalence of dental caries in school children in Al-Khobar, Saudi Arabia.
AB  - The author collected base-line data on the prevalence of dental caries in Al
      Khobar. He submits that examination of children's teeth should be part of
      clinical examinations by pediatricians.

PMID- 1401415
TI  - The cementomas--a clinicopathological re-appraisal.
AB  - The aim of this study was to assess whether sub-classification of cemental tumors
      was warranted and to define the clinicopathological features of the definitive
      entities. Our sample consisted of 127 cases which were divided into the following
      categories; gigantiform cementoma (84 per cent), cementifying fibroma (12 per
      cent), benign cementoblastoma (4 per cent). Gigantiform cementoma lesions were
      either single, multiple or florid and ranged in size from 1 to 10 cm. Most
      occurred in patients in their 6th and 7th decades who were black (78 per cent)
      and female (96 per cent). All lesions showed typical solid sheets of acellular
      cementum and some (22 per cent) were characterised by peripheral proliferative
      areas which were often indistinguishable from lesions of cementifying fibroma and
      periapical cemental dysplasia. Infection and sequestration was very common (54
      per cent). No cases of periapical cemental dysplasia were found and we suggest
      that this lesion is a variant of gigantiform cementoma. We believe cementifying
      fibroma to be part of the histomorphological spectrum of cemento-ossifying
      fibroma. Cemento-osseous dysplasia is a more accurate and appropriate term than
      gigantiform cementoma and we recommend the following classification for cemental
      'tumors': cemento-ossifying fibroma; cementoblastoma; cemento-osseous dysplasia,
      single, multiple and florid sub-types.

PMID- 1401416
TI  - Oral mucosal findings associated with chewing tobacco in Sweden--a clinical and
      histological study.
AB  - Twenty men of mean age 51,9 years who used Swedish chewing tobacco as their only
      tobacco habit were examined for clinical and histological changes. On average
      they had been chewing tobacco for 10,7 hours daily for 11,3 years. The most
      common clinical finding was a leukoedema-like change of the buccal mucosa at the
      site where the quid was held after chewing. Ten subjects showed changes similar
      to mild snuff-induced ones. Histological findings corresponded well with the
      clinical ones. It appears that oral mucosal changes associated with chewing
      tobacco in Sweden are discrete.

PMID- 1401417
TI  - Studies on the incorporation of lanthanides in dental hard tissues.
AB  - Rare earth elements (lanthanides)--known from chrystal-chemistry for the
      rehardening effect on apatites--have been tested previously for the possibility
      of their incorporation in dental enamel. From the non-toxic lanthanides cerium
      was incorporated under in vitro conditions in human dental enamel. In the present
      study, the incorporation of lanthanum (La), europium (Eu), samarium (Sa),
      ytterbium (Yb) and neodymium (Nd) in human permanent enamel, dentine and
      deciduous enamel has been investigated by neutron activation analysis. The
      lanthanides were incorporated--following the above sequence--in an increasing
      ratio into enamel and dentine, by forming new, more resistant rare earth elements
      containing apatite structures.

PMID- 1401418
TI  - Intraepithelial lymphocytes and Langerhans cells in the oral mucosa--dynamic
      aspects.
AB  - In the oral epithelium a constant population of non-epithelial immunocompetent
      cells--lymphocytes and Langerhans cells exists. 3025 such cells of the murine and
      542 of the normal human oral mucosa were documented photographically at the
      ultrastructural level. Location within the epithelium, morphological signs of
      locomotion, membrane configuration and labeling of the intercellular substance by
      ruthenium red were registered. About 40 per cent of the lymphocytes and 70 per
      cent of the Langerhans cells show signs of locomotion, predominantly in a lateral
      and basal direction. Occasional cells crossing the basal lamina are seen. Close
      apposition, or rarely a denticulated surface and lysis of desmosomes were
      present, both probably indications of cellular interactions. Ruthenium red
      labeling of the glycocalix is continuous forming a homogeneous layer between
      epithelial and non-epithelial cells and between intraepithelial cells, suggesting
      an even distribution of antigens and the lack of preformed spaces for
      intraepithelial cells. Murine and human intraepithelial cells exhibited no major
      differences.

PMID- 1401419
TI  - Pathogenesis of bony pocket formation around dental implants.
AB  - This study was undertaken to explain differences in the pathogenesis of
      periodontitis and peri-implantitis. Histological observations were made on
      experimental and human material obtained at autopsy. The sections were prepared
      without decalcification and without removal of the implants by the cutting and
      grinding technique. In some cases the implant was exposed but the mucosa
      surrounding it showed no inflammation. In other cases granulation tissue had
      formed around the implants resulting in a polypoid mass and the adjacent mucosa
      was inflamed. A discussion and comparison of the pathogenesis of periodontitis
      and peri-implantitis is given.

PMID- 1401420
TI  - The World Health Organization: histological typing of odontogenic tumours: an
      introduction to the second edition.

PMID- 1401421
TI  - Identification of common foreign material in postendodontic granulomas and cysts.
AB  - The present investigation was undertaken to identify commonly occurring foreign
      material in postendodontic periapical granulomas and cysts. 29 biopsies from such
      lesions with observed foreign material were routinely processed, stained with
      H&E, von Kossa and Calcofluor White and investigated by light, polarization and
      fluorescence microscopy. Applying back-scattered SEM images, the foreign material
      was subjected to energy dispersive X-ray analysis. 4 groups of foreign material
      were observed: 1. Black/brownish fragments and yellow/brown granules containing
      Au, Ag, Cu, Hg, Sn and Zn compatible with amalgam. 2. Fine black/brown/yellow
      granules compatible with endodontic sealer components revealing Ag, Ba, Bi, Cu,
      S, Ti and Zn. 3. Basophilic fragments compatible with Ca salts from Ca(OH),
      extruded periapically and containing Ca and P. 4. Elongated/rounded/oval/kidney
      shaped, colourless to slightly basophilic, birefringent structures revealing C
      and O and with a slit-like central canal and a bright, pale-blue fluorescence
      specific for cellulose.

PMID- 1401422
TI  - Hypertrophic lichen planus of the oral mucosa.
AB  - Hypertrophic lichen planus is a variant of the condition not previously
      recognised as occurring in the mouth. Four cases are described that have been
      followed clinically for 18, 9, 6 and 3 years. The histopathology is described.

PMID- 1401423
TI  - Oral manifestations of the HIV-infection: classification problems.
AB  - As more than 40 different oral lesions may be associated with the HIV-infection
      there is a need for classifying these lesions as a tool to be used in
      epidemiological studies. The paper deals with the classification proposed by the
      European Community.

PMID- 1401425
TI  - Lateral periodontal cystlike lesion--a discussion on the so-called botryoid
      odontogenic cyst.
AB  - A case of a so-called botryoid odontogenic cyst is presented. In the discussion
      the correctness of the terminology and classification of this lesion has been
      questioned, resulting in a plea for the use of the descriptive term "multicystic
      odontogenic lesion with histologic features of a lateral periodontal cyst" or,
      perhaps better "lateral periodontal cystlike lesion".

PMID- 1401424
TI  - A new concept of the pathogenesis of oral mucous cysts based on a study of 200
      cases.
AB  - A new hypothesis regarding the pathogenesis of mucous cysts of the oral mucosa is
      proposed. Based upon a histological study of 188 mucous cysts without epithelial
      lining out of a total of 200 cysts it is claimed that some cysts may not develop
      in any of the hitherto described ways as intraductal "mucous retention cysts" or
      extraductal "mucous extravasation cysts" or from destruction of acini due to the
      pressure of mucous caused by duct obstruction. It is suggested that some of the
      cysts, that are found to have developed intraglandularly, are caused by traumatic
      destruction of a large amount of glandular acini ("parenchymal destruction
      cysts") and continuous secretion from the remaining acini. The mucus from the
      disintegrated cells forms a pool, which in time is surrounded by a connective
      tissue capsule that contains remnants of parenchyma from the affected lobule.
      This parenchyma degenerates, and eventually the cyst shows the same histological
      picture as the "mucous extravasation cyst". It is argued that the presence of a
      feeder duct does not necessarily indicate an extravasation cyst, but may be seen
      in the "parenchymal destruction cysts" as well. Of the 188 cysts examined 20 (11
      per cent) were found to develop intraglandularly, and 36 (19 per cent) were
      considered probably to have developed intraglandularly.

PMID- 1401426
TI  - A model for epithelial growth and epithelium-connective tissue interaction
      studies.
AB  - The aim of this study was to evaluate implanted ectocervical biopsy material as a
      model for morphological studies of normal and abnormal epithelial growth and
      epithelial-connective tissue interactions. Forty-five specimens were implanted in
      the flanks of nude (immunodeficient) mice and harvested at 1, 2, 3 and 6 weeks.
      Superficial necrosis of the epithelial layer with retention of parts of the basal
      cell layer were evident at 1 and 2 weeks. At 2 weeks granulation tissue enclosed
      the bases of the implants. Regrowth of epithelium on the surfaces and from the
      edges of the specimens was seen at 3 weeks. At 6 weeks the specimens were
      revascularized and the majority coated with a well developed unkeratinized
      stratified squamous epithelial layer resembling the epithelium of the ectocervix.
      It is concluded that specimens of human ectocervix, implanted in nude mice, offer
      the possibility for morphological studies of normal and abnormal epithelial
      growth and, if experimental difficulties can be overcome, of the epithelial
      connective tissue interactions.

PMID- 1401427
TI  - Growth interaction between Candida albicans and Streptococcus salivarius: in
      vitro and in vivo studies.
AB  - Suppression of Candida albicans in the mouth by oral flora has been proposed as
      one of the mechanisms preventing candidal overgrowth. According to Liljemark and
      Gibbons (1973), Streptococcus salivarius plays a significant role in this
      process. The aim of this investigation was to study the growth interaction
      between C. albicans and S. salivarius in vitro and in vivo. An aerobic continuous
      flow system was used for the in vitro study. Pure and mixed cultures of C.
      albicans (NCPF 3118) and S. salivarius (NCTC 8618) were inoculated into a
      buffered medium containing either 0.1 per cent or 0.001 per cent glucose
      concentrations and incubated at 37 degrees C for 55 hours. Two in vivo
      investigations were undertaken using inbred germfree C3H mice. In the first, mice
      were exposed to a mixed suspension of S. salivarius and C. albicans for 48 hours.
      In the second the mice were exposed to S. salivarius for 48 hours. Fourteen days
      later they were contaminated with C. albicans. A comparison of growth curves
      showed no growth inhibition between the species. The in vivo studies showed that
      oral lesions from candidal infestation occurred in all mice. We were therefore
      unable to demonstrate in vitro or in vivo suppression of C. albicans in the
      presence of S. salivarius.

PMID- 1401428
TI  - Tooth and cusp size reduction in second molars.
AB  - The present study examined the cusp reduction pattern of molars in two San-Hybrid
      groups, namely, the Vassekela and Barakwena. Cusp and crownbase area measurements
      were undertaken on enlarged photographs of maxillary molars and on camera lucida
      drawings of mandibular molars. The protocone values for the Barakwena were
      significantly larger than those of the Vassekela and were also the largest of the
      four maxillary molar cusps (especially in M2). The metacone was the second
      largest cusp in M1, the paracone the second largest cusp in M2 and M3, while the
      hypocone was the smallest cusp in all maxillary molars. Maxillary crownbase areas
      were larger in the Barakwena than in the Vassekela but these differences were not
      statistically significant. The protoconid, entoconid and metaconid were the
      largest of the mandibular molar cusps. Generally, the cusp area values in first
      and third molars were larger in the taller Barakwena than in the shorter
      Vassekela. These differences were not statistically significant. In second
      molars, however, an unexpected finding was that crownbase and cusp areas (except
      the metaconulid) were significantly larger in the Vassekela than in the
      Barakwena. This study indicates that second molars show more cusp size
      differences in the two groups than do the other two molars. This may be regarded
      as a conservative tendency (Korenhof, 1960) in which case it would indicate that
      some second molar cusps are in a less active phase of evolutionary reduction than
      the same cusps in first and third molars.

PMID- 1401429
TI  - The heritage of fibrous polymers.

PMID- 1401430
TI  - Authorship of scientific articles.

PMID- 1401431
TI  - A survey of dental practice and equipment characteristics.
AB  - The aim of this study was to determine what would be regarded as essential
      equipment required for setting up a dental practice and the cost thereof. This
      information could be useful for the newly qualified dentist. Seventy five
      completed questionnaires returned from a randomly selected group of practising
      dentists were analysed to obtain this information. Equipment costs were obtained
      from a dental supply house and are tabulated. Guidelines recommended for setting
      up a practice include determining the type of service to be rendered, selecting
      the equipment required for this purpose, seeking expert financial advice and
      commencing the practice on a conservative basis with only the essential items of
      equipment.

PMID- 1401432
TI  - Plaque quantitation through protein measurement.
AB  - This study was undertaken to establish whether the quantitation of dental plaque
      protein by a dye-binding method (Coomassie G-250) may be used as an index of the
      amount of dental plaque sampled. Ten sites were sampled in 34 children on 5
      occasions at 4 month intervals. The mean protein concentration in 1391 plaque
      samples was 6.9 +/- 4.1 micrograms (micrograms) (mean +/- standard deviation). A
      three-way analysis of variance showed that the plaque protein concentration was
      similar at the different sampling sites in the same child (p = 0.14), but
      statistically significant differences were observed with respect to time of
      sampling (F = 36.24; p = 0.0001) and individual sampled (F = 5.69; p = 0.0001).
      These observations indicate that plaque bacterial counts may be expressed as
      units of protein concentration and this method may be useful to relate the number
      of viable bacteria to an estimate of the amount of plaque collected. This ratio
      allows standardisation for any variation in the amount of plaque collected.

PMID- 1401433
TI  - Tobacco and oral health. Smokeless tobacco--the fire without the smoke.

PMID- 1401435
TI  - Pulp biology research--is the frog still deaf?

PMID- 1401434
TI  - JWG14 statement on HIV/AIDS and dentistry.

PMID- 1401436
TI  - Unpublished NIDR-Eastman Dental Center prenatal fluoride (PNF) study.

PMID- 1401437
TI  - Salivary flow induction by buccal permucosal pilocarpine in anesthetized beagle
      dogs.
AB  - We tested whether permucosal delivery of pilocarpine nitrate could be used to
      elicit significant salivary secretion. Pilocarpine (pKa 6.6 at 37 degrees C) was
      applied as solutions (pHs 5.6, 6.6, 7.6; 15 mg/mL) to the buccal mucosa (2.8 cm2)
      of 6 anesthetized dogs. Saliva was collected continuously from cannulated
      submandibular and parotid ducts and blood sampled during and after drug
      administration. Plasma pilocarpine levels were determined by reversed-phase HPLC.
      Absorption rates were determined by use of data from separate zero-order
      intravenous infusions to the same dogs. Pilocarpine was buccally absorbed at a
      constant rate of 72.9 +/- 38.5 micrograms/kg/h following its application at pH
      7.6. At this pH of the drug solution, the time to appearance of pilocarpine in
      blood plasma was 0.31 +/- 0.08 h, and the time to appearance of salivary flow was
      0.86 +/- 0.32 h. A threshold dose of 32.9 +/- 7.5 micrograms/kg was required to
      induce secretion with the pH 7.6 drug, the steady-state submandibular flow rate
      was 0.14 +/- 0.11 mL/min/gland pair. Salivary flow induction was symmetrical and
      reached levels as high as 0.35 mL/min/submandibular gland pair without apparent
      tachyphylaxis. Results at pHs 5.6, 6.6, and 7.6 were consistent with the
      hypothesis that pilocarpine is primarily absorbed as un-ionized drug. The data
      indicate that transmucosal delivery of pilocarpine, avoiding "first pass" hepatic
      loss, may hold promise for the treatment of xerostomia.

PMID- 1401438
TI  - Fluoride concentrations in plaque, whole saliva, and ductal saliva after
      application of home-use topical fluorides [published eerratum appears in J Dent
      Res 1993 Jan;72(1):87].
AB  - It is now well-accepted that the primary anti-caries activity of fluoride (F) is
      via topical action. The retention of F in the mouth after topical fluoride
      treatment is considered to be an important factor in the clinical efficacy of F.
      The purpose of this study was to evaluate F levels in ductal saliva, whole
      saliva, and pooled plaque after treatment with topical F agents intended for home
      use. Ten consenting adults, mean (SD) age 31.0 (8.2) years, participated in all
      aspects of the study. Two days before each test, subjects received a professional
      tooth cleaning and subsequently abstained from all oral hygiene procedures to
      permit plaque to accumulate, and from the use of F-containing dental products.
      Treatments consisted of a placebo dentifrice (PD), fluoride dentifrice (FD; 0.24%
      NaF), fluoride rinse (FR; 0.05% NaF), and fluoride gel (FG; 1.1% NaF).
      Unstimulated whole saliva and pooled plaque were sampled at multiple points over
      a 24-hour period. In a separate experimental series, stimulated parotid saliva
      was sampled over a two-hour period after treatment. Fluoride levels generally
      followed the same pattern in whole saliva and pooled plaque samples, with FG > FR
      > FD > PD. Night-time F application resulted in prolonged F retention in whole
      saliva but not in plaque. Fluoride levels in parotid saliva were only slightly
      higher after F treatment and returned to baseline levels within two h. The
      results of this study indicate that the method of F delivery, the F concentration
      of the agent, and the time of application (daytime vs. night-time) are important
      factors influencing F levels in the mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401439
TI  - Composition of pooled plaque fluid from caries-free and caries-positive
      individuals following sucrose exposure.
AB  - The composition of pooled plaque fluid from five population samples was
      determined before and at selected times (7, 15, 30, and 60 min) after a 10%
      sucrose rinse. Subjects were grouped according to caries status (caries-free, CF,
      DMFS = 0; caries-positive, CP, DMFS > 10). Samples were also studied from white
      spot surfaces and from sound surfaces of the same mouths of two additional CP
      groups. Plaque fluid was isolated by centrifugation and analyzed for organic
      acids, inorganic ions (ion chromatography), and pH (microelectrodes). Prior to
      sucrose exposure, plaque fluids from the CF subgroups and from sound surfaces of
      the CP subjects had higher pH values than samples from CP subgroups and from
      white-spot surfaces, respectively; the ionic compositions were otherwise similar.
      Starved plaque fluids were also found to be supersaturated with respect to enamel
      and to a significantly greater degree in the CF samples, suggesting that CF
      plaque fluid may have a greater remineralization potential than CP samples.
      Following sucrose exposure, a rapid decrease in plaque fluid pH was observed,
      which corresponded primarily to lactic acid production. For all times examined,
      mean pH and DS(En) values were lower and lactic acid concentrations were higher
      in the CP samples than in the CF samples; noted differences were statistically
      significant at 7 min for pH and DS(En), and at 7, 15, and 30 min for lactic acid.
      Lower values of DS(En) suggest that plaque fluid from CP subjects had a
      measurably greater cariogenic potential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401440
TI  - Effect of xylitol consumption on the plaque-saliva distribution of mutans
      streptococci and the occurrence and long-term survival of xylitol-resistant
      strains.
AB  - Since the exposure of mutans streptococci to xylitol is known to select for
      xylitol-resistant (XR) natural mutants, the occurrence and long-term survival of
      such xylitol-resistant strains was evaluated in a cross-sectional sampling of
      participants of the Ylivieska xylitol study four years after the original two
      year experimental period. Paraffin-stimulated whole saliva was first collected,
      and then plaque was collected and pooled. The salivary and dental plaque mutans
      streptococci were enumerated after growth on TSY20B agar. The proportion of XR
      strains was determined by autoradiography with 14C-xylitol. A strong and
      significant correlation (r = 0.645 and p = 0.005) between the number of mutans
      streptococci in saliva and in dental plaque was observed in non-consumers of
      xylitol. Such a correlation totally disappeared (r = 0.098 and p = 0.612) in
      xylitol-exposed consumers (habitual and former xylitol-consumers). The proportion
      of the salivary XR mutants (35%) in non-consumers (n = 16) was significantly
      lower than in the xylitol-exposed consumers (79%) (n = 27), (p = 0.0001) or in
      former consumers (75%) (n = 13), (p = 0.0008) or in the habitual consumers (83%)
      (n = 14), (p = 0.004). The proportion of XR mutants in dental plaque was, on the
      average, much lower than in the corresponding saliva. The proportion of XR in the
      plaque of xylitol non-consumers was half of that of the xylitol-exposed group,
      but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1401441
TI  - Effect of delmopinol on the cohesion of glucan-containing plaque formed by
      Streptococcus mutans in a flow cell system.
AB  - Glucan-containing plaque was formed by Streptococcus mutans adhering to saliva
      coated glass slides in flow cells thermostated at 37 degrees C. The substrate was
      Brain Heart Infusion broth containing 1% sucrose and 10% sterile saliva. During
      the build-up of the plaque, which lasted for 29 h, the plaque was subjected to
      three two-minute exposures to either 0.1 mol/L sodium acetate buffer, pH 6.0, or
      the same buffer containing 6.4 mmol/L (0.2%) of the surface-active anti-plaque
      substance delmopinol hydro-chloride. The glass slides carrying the plaque were
      weighed, and plaques subjected to delmopinol treatment weighed only seven percent
      of the control plaques. The glass slides were then mounted in a beaker containing
      buffer, subjected to ultrasonication, and re-weighed. The delmopinol-treated
      plaques lost 59% of their wet weight upon sonication, while the controls lost
      only 19%. Control plaques having the same weight as delmopinol-treated plaques
      were not different from the control plaques grown for 29 h with regard to
      reduction of plaque weight after sonication. Transmission electron micrographs
      (TEM) showed a plaque dominated by globular or fibrillar matrix components in
      controls, while the delmopinol-treated plaque showed empty or unordered matrix
      areas between more densely packed cells. The TEM results were confirmed by
      scanning electron micrographs, which showed amorphous material associated with
      the bacterial cells in the control but not in the delmopinol-treated plaque. In
      conclusion, delmopinol reduced surface-associated glucan synthesis and lowered
      the cohesion of the plaque, indicating that glucan-containing plaque formed
      during repeated rinsings with delmopinol may be easier to remove by mechanical
      means than a non-treated plaque of this type.

PMID- 1401443
TI  - The relationship between level of mandibular pain and dysfunction and stage of
      temporomandibular joint internal derangement.
AB  - Temporomandibular joint internal derangement (TMJ ID) is the most common intra
      articular TM disorder and can progress from TMJ ID with reduction to TMJ ID
      without reduction. It is not known whether this anatomical progression is
      associated with increasing levels of mandibular dysfunction. The objective of
      this study was to determine whether the level of clinically detectable mandibular
      dysfunction was related to the stage of TMJ ID. Two clinicians examined 42
      subjects prior to bilateral TMJ arthrographic evaluation. The level of mandibular
      dysfunction was calculated by Helkimo's Clinical Dysfunction Index (Di) and the
      Craniomandibular Index (CMI). Statistical analysis revealed that the level of
      mandibular dysfunction as determined by the Di and CMI was not related to the
      arthrographic presence or absence of TMJ ID. Therefore, the clinician cannot
      assume that the level of mandibular dysfunction is directly related to the
      absence or presence of TMJ ID. Epidemiologically, the CMI and Di can be used only
      for estimation of the degree of mandibular dysfunction, since they do not provide
      direct information on a specific TM disorder.

PMID- 1401442
TI  - The influence of growth hormone on cell proliferation in odontogenic epithelia by
      bromodeoxyuridine immunocytochemistry and morphometry in the Lewis dwarf rat.
AB  - For investigation of how growth hormone affects tooth development,
      bromodeoxyuridine immunocytochemistry and morphometry were used for the study of
      cell proliferation in odontogenic epithelial cell layers. The number of cells in
      the S phase, as revealed by this technique, and in mitosis, were counted in
      Bouin's-perfused and paraffin-embedded undecalcified maxillary incisor enamel
      organs of normal rats, in growth-hormone-deficient dwarf rats, and in dwarf rats
      treated with growth hormone (66 micrograms/100 g body wt) twice daily for six
      days. Significantly fewer labeled nuclei, unlabeled nuclei, and total nuclei of
      various odontogenic epithelia were found in dwarf rats, but in dwarf rats treated
      with growth hormone, numbers of labeled nuclei equivalent to normal were found in
      the internal enamel epithelium, stratum intermedium, and Hertwig root sheath.
      Moreover, the mitotic index for pre-ameloblasts was 1.64 in normal rats, 0.92 for
      dwarf rats, and 1.66 for growth-hormone-treated dwarf rats (SD, 0.10). Other
      parameters--such as the labeling index and the ratio of positive to negative
      nuclei--were similarly related to GH status. Thus, growth hormone may play a role
      in the proliferation of the odontogenic epithelia in the rat.

PMID- 1401444
TI  - The relationship of undifferentiated mesenchymal cells to TMJ articular tissue
      thickness.
AB  - Undifferentiated mesenchymal (UM) cells, the progenitor cells of the cartilage
      layer, have been assigned a significant role in TMJ articular tissue maintenance.
      This was based on reports of UM cell reduction with increased soft-tissue
      thickness for the condyle and temporal component. However, the strength of this
      inverse relationship was not presented and remained unclear. The purpose of the
      present study was to assess the strength of the correlation between UM cell
      presence and soft-tissue thickness in young adult TMJs at autopsy. Sagittal
      histological sections from the central thirds of 50 joints were evaluated with
      respect to articular soft-tissue thickness, histological character, and UM cell
      presence in the condyle and temporal component. The superior sector of the
      condyle and the articular eminence showed the greatest variability in soft-tissue
      thickness and were the only areas to show localized UM cell absence. The eminence
      was the only location to show an inverse relationship between soft-tissue
      thickness and UM cell presence, and this was consistent in both an ANOVA (p =
      0.0016) and a Spearman correlation analysis. However, the strength of this
      correlation was only moderate (rho = -0.52), and no such relationship was
      observed in any other location. This study suggests that the relationship between
      UM cell presence and soft-tissue thickness is more complex than previously
      hypothesized and that the contribution of UM cells to articular tissue
      maintenance has been overstated, while other biological processes were
      overlooked.

PMID- 1401445
TI  - A seven-and-a-half-year survival study of resin-bonded bridges.
AB  - A clinical trial, concerning 203 resin-bonded bridges (RBBs), was performed for
      investigation of the influence of retainer-type and cementation materials on the
      survival of these restorations. The survival rates after a 7.5-year follow-up
      were 75% for anterior RBBs and 44% for posterior bridges. Etched metal RBBs (E
      bridges) were significantly more retentive than perforated RBBs (P-bridges); the
      survival rates were 78% and 63%, respectively. With respect to the cementation
      materials, Clearfil F, in combination with E-bridges, had the best overall
      survival (89%, anterior and posterior). Maxillary anterior RBBs were more
      susceptible to failure than mandibular anterior RBBs.

PMID- 1401446
TI  - Labile or surface pools of magnesium, sodium, and potassium in developing porcine
      enamel mineral.
AB  - The present study was undertaken to assess the labile or surface pools of Mg, Na,
      and K ions in porcine enamel tissues at various developmental stages. The enamel
      samples, corresponding to the outer and the inner secretory, the early maturing,
      and the mature hard enamel, were dissected from the labial sides of permanent
      incisors of 6- to 8-month-old piglets. Each enamel sample was extracted
      successively with solutions of de-ionized water and 50 mmol/L Tris-4 mol/L
      guanidine buffer (for removal of organic matrix proteins, mainly amelogenins).
      The labile (free or organically bound) pools of Mg, Na, and K were assessed by
      the total amounts of these ionic species extracted by the water and Tris
      guanidine buffer. The surface (adsorbed onto enamel mineral) pool of Mg was
      assessed directly by determination of the adsorption of Mg onto enamel mineral at
      various developmental stages. The results showed that: (i) 30-40% of the Mg in
      the secretory and early maturation enamel was in the surface pool (adsorbed onto
      the enamel mineral); (ii) 25 to 40% of the total sodium in the enamel samples was
      in labile forms; and (iii) most (around 70-80%) of the total potassium was
      readily extracted in water and appeared to originate from the enamel fluid; only
      marginal portions remained in the solids. The present adsorption studies also
      indicated that the maximum uptake of magnesium in the early maturation enamel was
      due mostly to an increase of the occupancy by Mg ions of adsorption sites on the
      crystal surfaces, which become accessible with a massive removal of enamel matrix
      proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401447
TI  - Correlates of success and failure in behavior therapy for dental fear.
AB  - Extreme dental fear and avoidance are universal problems, with severe adverse
      effects on the patient's oral health. Although behavior modification techniques
      were shown to be effective in the treatment of this problem, their success is by
      no means absolute. In the present article, the SCL-90 questionnaire was used for
      development of possible predictive measures for success and failure of behavior
      modification as a treatment for dental fear. Patients who failed in treatment
      through behavior modification were found to score significantly higher on the
      global score of Positive Symptom Distress Index (p < 0.01) and on individual
      subscales of somatization (p < 0.02) and psychoticism (p < 0.05) than patients
      who were treated successfully. The predictive value of chosen SCL-90 scales was
      71%. The results suggest that use of SCL-90 may be valuable for the prediction of
      success and failure of behavior modification as a treatment for dental fear and
      avoidance.

PMID- 1401448
TI  - Studies on the adhesion of glass-ionomer cements to dentin.
AB  - This study investigated the bonding mechanisms of glass-ionomer cement to dentin.
      The approaches included mechanical determination of bond strengths, analysis of
      surface morphology by means of scanning electron microscopy (SEM) and confocal
      microscopy, and measurement of chemical changes of fracture bond sites by means
      of x-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry
      (SIMS). The highest bond strengths were obtained with light-cured glass-ionomer
      cement. SEM and confocal images showed evidence of mechanical interlocking of
      cement in dentinal tubules. SIMS depth profiles confirmed the ion-exchange
      process between the light-cured glass-ionomer cement and the dentin surface. From
      corresponding XPS results, it was clear that the adhesion characteristics were
      significantly affected by light-curing and the chemical structure of the polymer.

PMID- 1401449
TI  - Effects of cement-curing modes on dentin bonding of inlays.
AB  - The aim of this in vitro study was to evaluate dentin adhesion after cementation
      of immediate direct "All Purpose" Hybrid (AP.H) composite inlays (Dentsply) and
      Cerec Dicor-MGC (Dentsply) inlays with the dentin adhesive Prisma Universal Bond
      2 (Dentsply) and the dual-curing Dicor-MGC luting composite (Dentsply). In 24
      extracted human molars, standard MOD cavities were prepared with one approximal
      margin located in enamel and the other one located in dentin. They were divided
      into four groups: (I) AP.H inlays, luting composite only, chemically cured; (II)
      AP.H inlays, luting composite, immediately-light-cured; (III) AP.H inlays, luting
      composite, initially chemically and delayed-light-cured (15 min); and (IV) MGC
      inlays, luting composite, initially chemically and delayed-light-cured (15 min).
      In vitro load cycles corresponding to five years of clinical stress followed.
      Initially and after specimens were loaded, the margins were analyzed
      quantitatively by SEM. The tooth/cement and cement/inlay interfaces were scored
      separately. The initial percentages of "continuous margin"--at both the
      tooth/luting composite and luting composite/inlay interfaces--were higher than
      94% for all groups. At the end of the load cycles, the quality of the margins at
      the tooth/luting composite interface significantly decreased for all groups. The
      highest decrease was found for the cervical margins located in dentin, where only
      37%-61% were scored as "continuous margin". The AP.H inlay/luting composite
      interface showed almost no change. At the MGC inlay/luting composite interface,
      the percentage of "continuous margin" decreased to 74%. After specimens were
      loaded, the percentage of "continuous margin" in dentin was lower than in enamel,
      despite the use of a dentin bonding agent (PUB 2).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1401450
TI  - Influence of ketones on selected mechanical properties of resin composites.
AB  - The present study investigated a concept for additional cross-linking of dental
      polymers, by which resistance to wear of resin composites might be increased.
      Bifunctional ketones were added to monomer mixtures, which were then made light
      curing and loaded with filler. The monomer mixtures were varied with respect to
      type and ratio of monomer and ketone. For measurement of possible effects of the
      cross-linking agents added, four mechanical properties of the experimental resin
      composites were determined. Addition of the bifunctional ketone diacetyl resulted
      in the following increases in mechanical properties: diametral tensile strength,
      11%; flexural strength, 29%; modulus of elasticity, 19%; and modulus of
      resilience, 50%.

PMID- 1401452
TI  - Focal infection revisited--the dentist as physician.

PMID- 1401451
TI  - Change in surface hardness of BisGMA/TEGDMA polymer due to enzymatic action.
AB  - The surface microhardness of specimens made of a BisGMA/TEGDMA polymer was
      measured before and during treatment for 60 days with phosphate buffer or
      phosphate-buffered esterase solution with an activity corresponding to the mean
      hydrolase activity of human saliva. The hardness of the buffer-treated specimens
      was unchanged during the incubation period, while that of the esterase-treated
      specimens decreased gradually. After about five days of treatment, no further
      change in hardness was observed for up to 60 days. Based on the difference in the
      calculated hardness of the specimens as a function of the applied load during
      measurement, it was estimated that the mean microhardness of the outermost
      surface layer of the esterase-treated specimens was diminished by about 15%,
      compared with that of the buffer-treated specimens. From these results, it was
      concluded that the wear resistance of a BisGMA/TEGDMA polymer is most likely
      diminished by hydrolases in saliva.

PMID- 1401453
TI  - Recent dental school experiences concerning HIV positive students--Northwestern,
      1991-92.

PMID- 1401454
TI  - The assessment of an HIV seropositive student at the University of Texas Health
      Science Center at San Antonio Dental School.

PMID- 1401455
TI  - Recent dental school experiences concerning HIV positive students: Creighton
      University.

PMID- 1401456
TI  - HIV infections: a personal perspective on the implications for dental education.

PMID- 1401458
TI  - Women dentists: 1992 and beyond.

PMID- 1401457
TI  - Women leaders in the business world.

PMID- 1401459
TI  - Issues and challenges facing the minority woman dentist.

PMID- 1401460
TI  - Mentors: who are they? Where are they? Do we need them?

PMID- 1401461
TI  - Women dentists at work: views from the glass ceiling.

PMID- 1401462
TI  - Workshop report: "women dentists as academicians: what are the issues?".

PMID- 1401463
TI  - Strengthening the NIDR-university relationship.

PMID- 1401464
TI  - Thoughts on the Council on Dental Education.

PMID- 1401465
TI  - Calling for a culture of collegiality in our colleges of dentistry.

PMID- 1401466
TI  - Sexual harassment. Commentary.

PMID- 1401467
TI  - Sexual harassment among female dentists and dental students in Texas.

PMID- 1401468
TI  - Sexual advances by patients in dental practice: implications for the dental and
      dental hygiene curricula.
AB  - The occurrence of patient initiated sexual advances toward dental health
      professionals has not previously been examined. Information from other health
      care specialties and reports from dental and dental hygiene students indicate
      that such advances do occur and that providers are rarely educated to deal
      effectively with them. Utilizing an anonymous survey of 300 Oregon dentists and
      300 dental hygienists, this study sought to quantify the frequency of patient
      initiated sexual advances toward dental professionals and to survey practitioners
      as to their reactions to and methods of dealing with such advances. The
      information provided by the 483 (81 percent) respondents indicates that up to 44
      percent of providers experience one or more patient verbal advances and up to 23
      percent of providers experience one or more patient physical advances during a
      five year period. These advances are a significant source of concern for many
      dental professionals. Based upon this information, implications for the dental
      and dental hygiene curricula are considered.

PMID- 1401469
TI  - Research directions in oral health promotion for older adults.
AB  - Health education and health promotion facilitate voluntary adoption of behaviors
      and provide educational, organizational, economic, and environmental supports for
      behaviors conductive to health. Health education and health promotion are
      complementary and any effort to eliminate oral disease requires both activities.
      Federal research initiatives in oral health promotion have encouraged more
      biomedical and behavioral research on oral health and aging through the
      establishment of research centers. Other initiatives have been established to
      speed the generation of basic and clinical research. Recent initiatives encourage
      research on aging and provide opportunities for oral health promotion during the
      coming decade. These include Healthy People 2000, the nation's health objectives
      for the decade; the NIH framework for the development of a strategic plan, and
      the NIDR Long-Range Research Plan, Broadening the Scope.

PMID- 1401470
TI  - Is dental education in step with current geriatric health promotion initiatives?
AB  - As dramatic changes in U.S. society continue to stress our health care system, we
      must consider new strategies to meet the oral health needs of older individuals.
      Several recent national initiatives, including the Healthy People 2000 health
      objectives and the Surgeon General's Workshop on Health Promotion and Aging,
      provide measurable health objectives and suggestions for educational activities
      in the area of geriatric oral health promotion. Using these and other recent
      documents like "Practitioners for 2005, An Agenda for Action for U.S. Health
      Professional Schools," we can evaluate current educational programs in geriatric
      dentistry, as well plan programs and health promotional activities that meet the
      future needs of dental professionals and the patients they serve.

PMID- 1401471
TI  - Oral health promotion for the older adult: implications for dental and dental
      hygiene practitioners.
AB  - The role of the dental and dental hygiene practitioner in geriatric oral health
      promotion can be viewed in terms of three questions. What purposeful or directed
      steps have been taken to improve oral health promotion? How can health promotion
      be improved? How can education and research help the practitioner? Professional
      associations, educators, researchers, school curricula, instructional programs,
      and dental products companies have tried to improve oral health promotion. At
      each level, communication of information and effective use of information has
      been compromised. Geriatric oral health promotion can be improved by increased
      understanding of: (1) health promotion concepts, (2) cultural and generational
      issues, (3) chronic oral conditions, (4) patients' perspective, (5) promoting
      behavior change, (6) listening skills, (7) patients' everyday realities, (8)
      integrating oral health issues into other health promotion activities, (9)
      creating easy to understand health education materials, and (10) lobbying for
      third party reimbursement for oral health promotion.

PMID- 1401472
TI  - Attitudes of dentists toward emerging competencies for health care practitioners.
AB  - Dentists' attitudes about the importance of formal training in a variety of
      skills were assessed as a part of the Pew Health Professions Commission
      initiative to help health professional schools prepare for the future. Through a
      telephone survey with a 54 percent participation rate, attitudes of a national
      sample of practitioners were determined concerning the importance of training in
      16 competencies that reflect skills, attitudes, and behaviors identified by the
      commission. Most respondents indicated that competency in treating and preventing
      disease, practicing ethically, communicating with patients, applying problem
      solving techniques, and continuing to learn were very important. Conversely, less
      than half of dentists indicated that competency in managing information,
      responding to cultural diversity, supporting community agencies, and working in
      managed care settings were very important. The opinions of graduates since 1980
      about their own training in the competencies tended to mirror their ratings of
      importance. These results demonstrate the continuing need for dental educators to
      consider prevailing opinion of practicing professionals as a part of any
      evaluation or planning effort.

PMID- 1401473
TI  - Curriculum guidelines for the development of predoctoral programs in
      temporomandibular disorders and orofacial pain.

PMID- 1401475
TI  - Curriculum guidelines for the development of continuing education programs in
      temporomandibular disorders and orofacial pain.

PMID- 1401474
TI  - Curriculum guidelines for the development of postdoctoral programs in
      temporomandibular disorders and orofacial pain.

PMID- 1401476
TI  - Genetic consequences of linkage between malathion resistance and an autosomal
      male-determining factor in house fly (Diptera: Muscidae).
AB  - The pattern of inheritance of genes conferring resistance to malathion and
      genetic consequences of linkage between an autosomal male-determining factor and
      resistance genes on the second chromosome were investigated in a strain of house
      fly, Musca domestica L., selected for malathion resistance. The second and fifth
      chromosomes contribute significantly to malathion resistance. The presence of a
      male-determining factor linked with the resistance genes on the second chromosome
      resulted in a strong sexual dimorphism in malathion resistance. We also observed
      that the male-determining factor changed its linkage relationship from the third
      linkage group to the second linkage group during the selection experiments.

PMID- 1401477
TI  - High levels of pyrethroid resistance in horn flies (Diptera: Muscidae) selected
      with cyhalothrin.
AB  - Lambdacyhalothrin cattle ear tags controlled horn fly, Haematobia irritans (L.),
      for 14 wks or longer during 1986-1988 in Georgia, USA. In 1989 and 1990, control
      of < 50 horn flies per side of cow was achieved for < or = 4 wk because of high
      levels of pyrethroid resistance in horn flies selected with lambdacyhalothrin.
      The highest resistance ratios (RRs) were seen in 1989. These were 498 for
      lambdacyhalothrin; 92,000 for fenvalerate; and 54 for permethrin. RRs for
      cypermethrin as high as 8,800 were estimated in 1990 when the RR for fenvalerate
      was only 1,060. No cross-resistance to diazinon was detected. These high levels
      of pyrethroid resistance seem to have a large component of metabolic resistance.
      Synergistic coefficients as high as 3,600 were determined by addition of
      nonlethal amounts of piperonyl butoxide. Resistance development in a no
      pyrethroid-use area indicates movements of > or = 3km by sufficient numbers of
      horn flies can significantly change the RR.

PMID- 1401478
TI  - Detection of insecticide resistance in the German cockroach (Dictyoptera:
      Blattellidae) with glue-toxin traps.
AB  - Glue that contained an insecticide was evaluated for its ability to yield useful
      toxicological data for German cockroaches, Blattella germanica (L.). Toxicities
      of three classes of insecticides were evaluated by topical applications (LD50)
      and exposure to insecticide-impregnated glue (LC50). Cockroaches that were
      resistant to topical insecticide applications were also resistant to the glue
      formulation. Reliability was greatest when mortality was scored 40 to 48 h after
      the cockroaches were placed on the glue. This method should be adaptable for
      insecticide resistance monitoring of German cockroaches.

PMID- 1401479
TI  - Effects of cyromazine on reproduction and offspring development in Lucilia
      cuprina (Diptera: Calliphoridae).
AB  - The effects of cyromazine on reproduction and subsequent hatch and larval
      developmental in Lucilia cuprina (Wiedemann) were examined by feeding the
      compound in water to adult flies at concentrations up to 100 ppm. Cyromazine did
      not interfere with oviposition or hatch; however, subsequent larval development
      was strongly inhibited in a concentration-dependent manner.

PMID- 1401480
TI  - Vertebrate safety of Clostridium bifermentans serovar malaysia, a new larvicidal
      agent for vector control.
AB  - The safety of bacterial cells of Clostridium bifermentans serovar malaysia, which
      is highly toxic to mosquito larvae, was tested on mice, guinea pigs, rabbits, and
      goldfish. Inoculations of at least 1 x 10(8) cells per animal by routes
      recommended by World Health Organization (subcutaneous, percutaneous, inhalation,
      force-feeding, intraperitoneal, intravenous) and tests of subacute toxicity,
      anaphylactic shock, persistence in heart blood, and virulence by successive
      passages, were performed on mice, guinea pigs, or both. Growth was monitored for
      1 mo before necropsy. Ocular irritation and skin scarification were tested with
      rabbits. C. bifermentans serovar malaysia did not induce any mortality or
      abnormal reactions in mammals at a dose 1,000 times higher than the level
      established by W.H.O. for the demonstration of safety. Bacterial cells are not
      toxic to goldfish at a dose 1,000 times higher than the LD50 for the target
      mosquito larvae. We conclude that C. bifermentans serovar malaysia bacterial
      cells are safe for laboratory mammals and goldfish.

PMID- 1401481
TI  - Monitoring adult populations of the screwworm (Diptera: Calliphoridae) with
      feeding stations baited with liver.
AB  - Populations of the screwworm, Cochliomyia hominivorax (Coquerel), were monitored
      by capturing adults with hand nets and rooted liver set on the ground. Adults
      were marked and released. During the 61-d study conducted in a tropical dry
      forest in the dry season (January to March 1989), 2,640 individual females and
      460 individual males were recorded at the four liver-baited stations. The total
      number of visits by females was 5,769 and by males 510. The mean number of
      unmarked adults per day was 44.1 females and 7.6 males in an area of
      approximately 2.59 km2. The mean percentage of marked flies that were recovered
      was 64.3%. The mean number of feeding stations visited, times recaptured, and
      days in the study area by individual females was 2.1, 2.4, and 4.5, respectively.
      Daily visitational patterns by both sexes at the feeding stations were bimodal
      with peaks occurring between the hours of 0730 to 0859 and 1500 to 1629. Flies
      were most active when the mean temperature was 29.9 degrees C; the majority of
      the visits occurred when air temperatures were between 26 and 33 degrees C. Most
      females attracted to feeding stations were nulliparous (70.7%) and mated (69.7%).
      Our results suggest that observing adults at feeding stations is a reliable
      method of obtaining data on the behaviour and population dynamics of indigenous
      populations of screwworm adults in tropical habitats. Although this method was
      labor intensive, the amount of data gleaned from the manipulation of wild
      populations more than compensated for such costs.

PMID- 1401482
TI  - Sublethal effects of insecticides on adult longevity and fecundity of German
      cockroaches (Dictyoptera: Blattellidae).
AB  - The effects of sublethal concentrations of chlorpyrifos, cyfluthrin, and
      hydramethylnon on adult longevity and fecundity of German cockroaches, Blattella
      germanica (L.), were investigated. Longevity of males declined linearly with
      increasing doses of insecticide. An LD50 of cyfluthrin decreased male longevity
      by 52%, whereas an LD50 of hydramethylnon reduced male longevity by 81%.
      Longevity of females increased linearly with increasing sublethal doses of
      chlorpyrifos, whereas all doses of both cyfluthrin and hydramethylnon decreased
      longevity of females. Fecundity increased linearly with increasing sublethal
      doses of chlorpyrifos. Number of oothecae formed, oothecae hatched, and number of
      offspring produced in each ootheca increased with increasing sublethal
      concentrations of chlorpyrifos. In contrast, fecundity declined with increasing
      sublethal concentrations of cyfluthrin and hydramethylnon. Formation of the first
      ootheca occurred approximately 8 d after mating for untreated females but
      generally longer with sublethal concentrations of all insecticides. The period
      between oothecae hatch and the formation of subsequent oothecae increased with
      successive oothecae in all treatments.

PMID- 1401483
TI  - Calf milk replacers as substitutes for milk in the larval diet of the screwworm
      (Diptera: Calliphoridae).
AB  - The effect of calf milk replacers as substitutes for nonfat dry milk in the
      larval diet of the screwworm, Cochliomyia hominivorax (Coquerel), was determined
      in the laboratory. Pupal weight and fecundity of females were significantly
      greater than the control with some of the formulations tested. Larval crawl-off
      patterns for all diets were similar. Pupal weights were significantly affected
      only on day 1 of the 4-d crawl-off period. Among the formulations of calf milk
      replacer, Gold Label brand products showed the most promise as substitutes for
      the nonfat dry milk presently used in the screwworm production facility. Use of
      calf milk replacers would lead to a yearly savings of 39.3% in the cost of the
      dietary milk component. At a production level of 250 million flies weekly, this
      substitution would save approximately $338,000 dollars yearly.

PMID- 1401484
TI  - Effects of stable flies (Diptera: Muscidae) and heat stress on weight gain and
      feed efficiency of feeder cattle.
AB  - Cattle respond to the feeding of stable flies, Stomoxys calcitrans (L.), by
      bunching to protect their front legs. This bunching can increase heat stress
      which indirectly accounts for much of the reduction in cattle weight gains. We
      used fly-screened, self-contained feedlot pens which allowed regulation of fly
      populations feeding on cattle. The indirect fly effects (bunching and heat
      stress) accounted for 71.5% of the reduced weight gain. The direct effect of the
      biting flies and energy loss involved in fighting flies accounted for 28.5% of
      the reduced weight gain.

PMID- 1401485
TI  - Optimization of murine keratinocyte culture for the production of graftable
      epidermal sheets.
AB  - The aim of the present study was to optimize murine epidermal cell cultures in
      order to obtain graftable sheets. Newborn (1-3 days old) Balb/c mice skin were
      used to optimize culture media and plating cell concentration, then epidermal
      sheet production, and grafting. Epidermal cells were plated at various
      concentrations in different culture media containing low (0.1 mM) or high
      (greater than 1 mM) Ca2+ levels. After a 3 day culture at the 10(4) cells/cm2
      plating cell concentration, the percentage of differentiated cells was more than
      80% in the high Ca2+ culture medium and less than 50% with bulky cells in the low
      Ca2+ culture medium. Under these conditions confluence was not obtained. At the
      10(5) cells/cm2 seeding inoculum, the percentage of confluence increased to 95
      100% during the first 72 h of culture in both high and low Ca2+ culture media.
      Three-day-old culture showed stratified multilayer epidermal sheets in the high
      calcium medium, and monolayer epidermal sheets were present in the low calcium
      medium after seeding keratinocytes in fibronectin precoated flasks. Seven days
      after plating, post confluent cultures were composed of a high percentage of
      differentiated cells (90%) with an increase in shedding cells in the medium.
      Considering the above morphological observations, sheets obtained with 10(5)
      cells/cm2 in MCDB-153 (A), DME-HAM (B) or GMEM (C) media after 3 days in culture
      were grafted. Twenty days after grafting, histological analysis of biopsies
      showed an epidermal structure and organization comparable to normal murine
      epidermis without hair follicles. Epidermal transplants showed a complete
      basement membrane, hemidesmosomes, and tonofilament bundles. Sheets obtained
      after seven day culture in all media showed lower coverage of the wound bed.
      These studies point out the importance of the plating cell and Ca2+
      concentrations, and the culture time for murine keratinocyte confluence and
      differentiation to obtain graftable epidermal sheets.

PMID- 1401486
TI  - Photosensitivity in atopic dermatitis: demonstration of abnormal response to UVB.
AB  - It is a well-known fact among clinicians that sunlight may exacerbate atopic
      dermatitis (AD), but little is known beyond that. In a preliminary study
      investigating this phenomenon, 19 patients with AD were selected for phototests.
      All of them had a normal minimal erythema dose (MED). However, 3 patients (15.7%)
      demonstrated abnormal cutaneous responses 24-72 h after provocation with
      ultraviolet light B (UVB). None of the patients had a positive response to pure
      ultraviolet light A (UVA) irradiation of up to 9 J/cm2. The photobiological
      results of this study confirm the existence of photosensitivity in AD and
      indicate that UVB wavelengths are responsible for it.

PMID- 1401487
TI  - Organ culture of human hair follicles derived from different areas of the body.
AB  - Whole human hair follicles derived from the scalp, chin, axilla, and pubis were
      organ cultured. The hair follicles were dissected from excised normal skin pieces
      and placed in 1.0 ml of incubation medium in a closed 5 ml glass tube under an
      atmosphere of air + 5% CO2. The tube was rolled at 15 rpm and 36 degrees C. The
      hair follicles from each area of the body grew linearly for about 6 days, both in
      serum-plus and serum-free media with or without fibroblast growth factor (FGF).
      The growth rates were slightly slower in serum-free media than in serum-plus
      media. No significant differences in the growth rates of hair follicles in organ
      culture were seen in different areas of the body. FGF did not affect the growth
      rate or the culture term of the hair follicles in vitro. This is the first report
      of human hair follicles derived from chin, axilla, and pubis growing well for
      about a week in organ culture.

PMID- 1401488
TI  - Genetic polymorphisms in the fourth component of complement (C4) and in properdin
      factor B (BF) in Japanese patients with palmoplantar pustulosis.
AB  - Genetic polymorphisms in the fourth component of complement (C4) and in properdin
      factor B (BF) were investigated in 49 and 32 Japanese patients with palmoplantar
      pustulosis (PPP), respectively. C4B2 was significantly increased in frequency,
      whereas no significant deviations were detected in BF compared with the controls.
      These results may indicate that complement polymorphisms are involved in the
      pathogenesis of PPP.

PMID- 1401489
TI  - An epidemiological study of methicillin-resistant Staphylococcus aureus (MRSA)
      isolated from medical staff, inpatients, and hospital environment in one ward at
      our hospital.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important
      causative microorganisms for nosocomial infections. Recently, the incidence of
      isolation of MRSA has been increasing every year in Japan and is, notably, much
      more frequently found in inpatients than in outpatients. Therefore, we have done
      epidemiological studies of MRSA isolated from medical staff, inpatients, and the
      hospital environment in one ward of our hospital. Thereafter, we examined the
      antibiotic susceptibility (ABPC, DMPPC, CET, CMZ, IPM, GM, MINO, OFLX, EM, CLDM,
      VCM), phage typing, and coagulase typing of these MRSA. MRSA were isolated more
      frequently from anterior nares of inpatients than from doctors and nurses. MRSA
      were isolated more frequently from the environment near carriers of MRSA.
      Coagulase type II and phage type N.T. (not typable) were the dominant types of
      MRSA in our hospital (69% and 61%). MRSA strains were resistant to most
      antibiotics with a few exceptions (VCM, IPM, CMZ, CET). The high isolation
      frequency of MRSA in our hospital seems to suggest that inpatients who are
      carrying MRSA spread MRSA throughout the hospital environment and that the
      anterior nares of inpatients are the major MRSA harbor.

PMID- 1401491
TI  - Necrolytic migratory erythema in glucagonoma syndrome.
AB  - A 32-year-old female Chinese presenting with typical features of necrolytic
      migratory erythema due to glucagonoma syndrome is reported. The clinical,
      biochemical, histopathological, and electron-microscopic findings are described.
      Various different aspects of this rare entity are discussed.

PMID- 1401492
TI  - A case of contact dermatitis due to methylprednisolone.
AB  - A 46-year-old woman developed contact dermatitis on her face after application of
      an ointment containing 0.1% methylprednisolone and 0.35% fradiomycin. Her patch
      test result was positive with methylprednisolone, but not with fradiomycin. No
      cross-reactions were observed after conducting patch tests with 17 different
      topical corticosteroids including prednisolone.

PMID- 1401493
TI  - Acne fulminans and 13-cis-retinoic acid.
AB  - We report a case of acne fulminans occurring during treatment with 13-cis
      retinoic acid for cystic acne. Continuing the treatment with 13-cis-retinoic acid
      without systemic steroid eventually cleared the systemic manifestations and skin
      lesions. We review the literature and discuss its pathogenesis.

PMID- 1401490
TI  - Triple cancers in the urogenital area of a patient with aplastic anemia.
AB  - Three epithelial neoplastic lesions, perineal Bowenoid papulosis, uterine
      cervical carcinoma, and bladder transitional cell carcinoma, which occurred in a
      mildly immunosuppressed patient who had aplastic anemia were studied for human
      papillomavirus (HPV) infection. In the Bowenoid papulosis, HPV type 16 DNA was
      identified by polymerase chain reaction (PCR) and by in situ hybridization (ISH).
      In contrast, in the uterine cervical carcinoma, HPV 16 was not detected, although
      possibly another unidentified type of HPV in the lesion was suggested by the ISH
      findings. In the bladder transitional cell carcinoma, neither papillomavirus
      genus-specific (PGS) antigen nor HPV DNA was found.

PMID- 1401494
TI  - Hereditary benign telangiectasia: two case reports.
AB  - We present two cases of hereditary benign telangiectasia (HBT) in which the
      genetic findings are compatible with an autosomal dominant hypothesis. The
      lesions persisted indefinitely for many years without effect on the general
      health of the patients. The term hereditary benign telangiectasia distinguishes
      the disorder from the more serious hereditary hemorrhagic telangiectasia (Rendu
      Osler-Weber). The etiology remains unknown. The condition causes only cosmetic
      disability and is not associated with any other diseases.

PMID- 1401495
TI  - Effects of butylated hydroxyanisole on ornithine decarboxylase activity induced
      by ultraviolet-B and PUVA in mouse skin.
AB  - The effects of butylated hydroxyanisole (BHA), a representative phenolic
      antioxidant, on the activity of ornithine decarboxylase (ODC, an indicator of
      tumor promotion and epidermal hyperproliferation) induced by ultraviolet-B (UVB)
      or PUVA in mouse skin were investigated. By topical application of BHA (55
      mumol), PUVA-induced ODC activity was suppressed by about 60% at both 12 h and 24
      h after treatment. In contrast, BHA failed to suppress UVB-induced ODC activity
      in mouse skin. These results suggest that the induction of ODC activity by UVB or
      PUVA is mediated by different pathways.

PMID- 1401496
TI  - Ultrastructural aspects of infiltrated eosinophils in bullous pemphigoid.
AB  - By scanning (SEM) and transmission electron microscopy (TEM), we evaluated the
      infiltrated eosinophils in lesions at various stages of clinical development from
      patients with bullous pemphigoid (BP) and eosinophilia. Visualized by SEM,
      numerous inflammatory cells migrated through the cutaneous basement membrane into
      the cavity of newly formed blisters 12 to 24 hrs after formation. Many migrating
      cells attached to the reverse side of the bullous cavity, and some basal cells
      shed into the cavity. As the bullae developed 24 to 48 hrs after formation, the
      reverse surface of the bullous cavity became predominantly composed of these
      migrating cells and the exposed squamous cells. The migrating cells had villi,
      ruffles and ridge-like profiles on their surfaces, which were suggested
      eosinophils. By TEM in the same lesions, many morphologically activated
      eosinophils were seen to have passed through the basement membrane into the newly
      formed blisters; they exhibited spheroidal cytoplasmic granules with less dense
      crystalloid cores and intracellular channels. Eosinophils infiltrating in the
      developed bullous cavity directly adhered to basal cells and released their
      granule contents onto these target cells. These findings suggest that
      inflammatory cells, especially eosinophils, may amplify the formation of dermal
      epidermal separation in BP lesions.

PMID- 1401497
TI  - Ingrown toenails: an evaluation of elevating the nail bed-periosteal flap.
AB  - Many procedures to correct ingrown toenails are available; however, they cannot
      avoid recurrence and nail deformities. We have performed a procedure which
      corrects ingrown toenail without reducing the width of the nail plate by
      elevating the nail bed-periosteal flap. Sixty patients were observed for longer
      than six months and exhibited excellent results. Only two cases of incurvated
      nails (2) required re-operation.

PMID- 1401498
TI  - Serum hormone levels in men with severe acne.
AB  - In order to evaluate the hormonal milieu in young men with severe acne, we
      measured serum estradiol (E2), total testosterone (T), free testosterone (FT),
      dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex
      hormone binding globulin (SHBG) levels in sixteen male patients aged 20-30 years
      with severe acne, including twelve cases of nodular-cystic acne, and in seventeen
      age-matched normal controls. There were no significant differences in the serum
      levels of T, FT, DHT, DHEA-S, or SHBG between the patients and the controls, but
      serum E2 was significantly higher in the patient population. Thus, the
      hemodynamics of serum androgens in male patients with acne do not seem to differ
      significantly from that of normal controls. Elevated E2 levels might affect the
      inflammatory response of acne vulgaris through the release of thymic hormones, as
      reported in the literature.

PMID- 1401499
TI  - Immunohistochemical characterization of cellular infiltrates in squamous cell
      carcinoma and Bowen's disease occurring in one patient.
AB  - We investigated populations of the infiltrating cells in Bowen's disease (BD) and
      squamous cell carcinoma (SCC), both of which arose in the same patient, using the
      Avidin-Biotin-peroxidase complex method with eight monoclonal antibodies. T
      lymphocytes were most predominant among infiltrating cells; NK cells, B cells,
      and monocytes were rarely seen in either BD or SCC. Analysis of subsets of the
      infiltrating T lymphocytes revealed that the number of suppressor/cytotoxic (s/c)
      T cells was twice that of helper/inducer (h/i) T cells in BD, while the number of
      s/c T cells was lower than that of h/i T cells in SCC. The immunohistochemical
      results in the present case differed from those of predominant infiltration of
      h/i T cells and of s/c T cells in three other reports of BD and SCC. These
      results suggest that the population of the cellular infiltrates may be modulated
      by the nature of tumors and by the immuno-competent state of the hosts.

PMID- 1401500
TI  - Fulminant dermatomyositis after removal of a cancer.
AB  - Dermatomyositis developed suddenly in a diabetic patient with CREST syndrome
      after the removal of a malignant tumor. Scrupulous physical examination excluded
      further systemic or cutaneous involvement. We raise certain still unsolved
      aspects regarding the association between dermatomyositis and neoplastic
      disorders.

PMID- 1401501
TI  - Fasting diet therapy for chronic urticaria: report of a case.
AB  - We used fasting diet therapy with a 28-year-old woman with chronic urticaria who
      responded only to systemic administration of glucocorticosteroids. The rashes
      began to decrease on the third therapeutic day and completely disappeared on the
      11th day. Although the eruptions relapsed three days after the termination of the
      therapy, they were milder than previous ones. We also discussed the possible
      efficacy of fasting diet therapy for chronic urticaria as reported in the
      literature.

PMID- 1401502
TI  - Giant condyloma acuminatum in a baby boy.
AB  - A giant condyloma acuminatum developed on the penis of a one and a half-year-old
      Japanese boy in two months. The histological features of this tumor were
      compatible with those of ordinary condyloma acuminatum. Although we detected the
      presence of human papilloma virus (HPV) type 16 by using the polymerase chain
      reaction system, we could not rule out the possibility that this HPV was present
      concurrently with other HPV types that cause condyloma acuminatum. The lesion was
      successfully treated with cryotherapy and topical application of 5% fluorouracil
      ointment under occlusion.

PMID- 1401503
TI  - Subtle differences in the morphology of bullous lesions between epidermolysis
      bullosa acquisita and bullous pemphigoid.

PMID- 1401504
TI  - Restriction of cicatricial pemphigoid antigens to the lamina densa: confirmation
      by indirect immunoelectron microscopy.
AB  - Circulating anti-basement membrane zone (BMZ) antibodies in a patient with
      cicatricial pemphigoid (CP) were examined using an indirect immunofluorescence
      test, indirect immunoperoxidase electron microscopy, and Western blot analysis.
      An indirect immunofluorescence test on salt-split skin revealed that the anti-BMZ
      antibodies reacted solely to the dermal side at the separating epidermal-dermal
      interface, and indirect immunoelectron microscopy on intact skin indicated
      localization of the corresponding antigens (CP antigens) over the lamina densa
      and within the lower half of the lamina lucida; there were no CP antigens beneath
      a melanocyte. Indirect immunoelectron microscopy on salt-split skin demonstrated
      that the CP antigens were partly dissociated from, but restricted to, the lamina
      densa. Western blot analysis showed no differences in molecular weight between
      the CP antigens and bullous pemphigoid (BP) antigens. CP antigens, as detected by
      this patient's serum, appear to be constituted of molecules quite similar to BP
      antigens, but with different epitopes. CP antigens may be shed from basal cells
      and locate in the area of anchoring filaments, where they play a role in
      connecting basal cells to the underlying lamina densa.

PMID- 1401505
TI  - The induction of ornithine decarboxylase in human epidermis is independent of
      lipoxygenase and cyclo-oxygenase pathways.
AB  - In vivo studies in rodents suggest that prostaglandins and/or leukotrienes are
      involved in the epidermal induction of ornithine decarboxylase (ODC). Recently,
      we have shown that, in human epidermis, prostaglandins are not involved in this
      process. Here we report the role of leukotrienes in epidermal ODC induction in
      human skin. Topical flufenamic acid (Dignodolin), vehicle, or nothing was applied
      under plastic occlusion to three sites on the backs of healthy volunteers. This
      was followed 1 h later by Sellotape stripping. After renewed application and
      occlusion for 8 h, biopsies were carried out for the estimation of ODC levels.
      There were no significant differences in the levels of ODC between the flufenamic
      acid treated and control sites. To confirm this finding, test sites were
      irradiated with 3 MED of UVB. This was immediately followed by the application of
      flufenamic acid, vehicle, or nothing to the three irradiated sites. After 8 h,
      biopsies were taken, and the levels of ODC were again similar in the flufenamic
      acid- and the vehicle-treated sites. The data indicate that, following Sellotape
      stripping or UVB irradiation, neither lipoxygenase not cyclooxygenase products
      contribute to the in vivo induction of ODC in human epidermis.

PMID- 1401506
TI  - The comparison of sun protection factor values with different light sources.
AB  - Sun protection factors (SPFs) were evaluated with three light sources (sunlight,
      a xenon arc solar simulator, and fluorescent lamps) in indoor and outdoor
      studies. Two types of light, UV-A+B and UV+Visible, were obtained from the solar
      simulator. The untanned backs of twenty-four healthy male volunteers were used as
      test sites. A broad spectrum sunscreen containing SPF 6, according to the
      manufacturer, was used. The sunscreen tested was applied at 2 mg/cm2. The actual
      SPF values were 4.8 with sunlight, 6.0 with UV-A+B, 4.9 with UV+Visible, and 11.8
      with fluorescent lamps. There were no significant differences between the SPF
      values with sunlight and those with the solar simulator; the SPF value for
      fluorescent lamps was significantly higher. The SPF with UV-A+B of the solar
      simulator was similar to that with sunlight; the use of this light served to
      reduce pain on tested subjects. Therefore, UV-A+B from the solar simulator seems
      to be the most appropriate artificial light source for evaluating sunscreens.

PMID- 1401507
TI  - Juvenile dermatomyositis: a statistical study of 114 patients with
      dermatomyositis.
AB  - We conducted a statistical review of 114 cases of dermatomyositis (DMS) treated
      primarily at the Department of Dermatology at Nagoya University Hospital over 27
      years from 1965 to 1991 in order to determine the primary characteristics of
      juvenile DMS with the following results. 1) Juvenile DMS was found slightly more
      often in males than females; the male-to-female ratio was 1.4:1. Therefore,
      unlike adult DMS with its preponderance of females, there was no clear gender
      predominance. 2) Muscular manifestations tended to follow the appearance of
      cutaneous manifestations, but the frequency of minor muscular manifestations was
      high over the entire course of the disease. 3) Laboratory findings showed
      increases in serum aldolase and serum creatinine kinase with significant
      frequency when compared with adult patients (p < 0.01 and p < 0.05,
      respectively). Elevated serum aldolase most often occurred prior to or at the
      time of the appearance of muscular manifestations, suggesting its usefulness in
      early diagnosis. The positive rates for the antinuclear antibody on HEp-2 cells
      and anti-DNA antibody were significantly lower in children than in adults (p <
      0.001 and p < 0.05, respectively). 4) There were no cases of juvenile DMS
      complicated by malignant tumors, interstitial pneumonia, or pulmonary fibrosis.
      There were also no deaths, and the rate of "remission or improvement" was
      significantly higher than in adult DMS cases (p < 0.05). Adult cases which
      remained the same or worsened usually presented with intractable muscular
      manifestations. In children, however, the cutaneous manifestations were more
      difficult to treat.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401508
TI  - Electron microscopic X-ray microanalysis of metals deposited in oral mucosa.
AB  - A 35-year-old woman exhibited bluish-brown discoloration of her buccal mucosa
      suggesting malignant melanoma. Histopathological examination revealed that the
      pigment was not melanin but caused by metal deposits. Electron microscopically,
      metallic particles were located on the lamina densa of basal laminae at mucosal
      epithelium, nerve fibers, and blood vessels and on the microfilaments of elastic
      fibers as well as in macrophages and fibroblasts. Electron microscopic point X
      ray microanalysis revealed that these metallic particles were composed of Ag, Se,
      Fe, Co, Cu, and S. Analysis suggests that these metals were derived from dental
      amalgam and that the discoloration was caused by amalgam tattoo.

PMID- 1401509
TI  - Eccrine hidrocystoma: two cases of Robinson and Smith types.
AB  - Two cases of eccrine hidrocystoma, one of which is a "classic" Robinson type and
      the other a Smith type, were reported. The walls of both cysts consisted mainly
      of two layers of flat or low cuboidal epithelial cells with eosinophilic
      cytoplasm. Immunostaining for S-100 protein was negative in the cells of the cyst
      wall of the Robinson type and only weakly positive in the inner luminal layer of
      the Smith type. Electron microscopically, the Smith type showed double-layered
      cuboidal lining and cell membrane interdigitations as junctions of neighboring
      cells without any characteristics of the secretory segment of sweat glands,
      indicating substantial similarity to those of the intradermal portion of the
      eccrine sweat duct.

PMID- 1401510
TI  - A case of adult T cell leukemia with bullae in the palmoplantar regions followed
      by a crisis.
AB  - A 48-year-old Japanese female who had had chronic ATL for 4 years suddenly
      developed vesicles on the palms and soles. Histologically, these bullae were
      specific lesions of ATL. After a tendency toward improvement, a crisis appeared
      with increases in the following: peripheral white blood cells, atypical
      lymphocytes, CD25 positive cells, serum LDH, and soluble IL-2R. Palmoplantar
      bullae, a rather rare finding, may be indicative of a following crisis.

PMID- 1401511
TI  - A case of trichoadenoma arising in the buttock.
AB  - A 41-year-old Japanese man with trichoadenoma on his buttock was described.
      Histological examination showed numerous horn cysts and some tumor islands
      consisting entirely of eosinophilic epithelial cells. A review of 24 reported
      cases of trichoadenoma revealed that most of them developed on the facial region
      (14 of 24 cases, 58%); the buttock (6 of 24, 25%) was the next most common site.

PMID- 1401512
TI  - The influence of talker differences on vowel identification by normal-hearing and
      hearing-impaired listeners.
AB  - Vowel identification was tested in quiet, noise, and reverberation with 20 normal
      hearing subjects and 20 hearing-impaired subjects. Stimuli were 15 English vowels
      spoken in a /b-t/context by six male talkers. Each talker produced five tokens of
      each vowel. In quiet, all stimuli were identified by two judges as the intended
      targets. The stimuli were degraded by reverberation or speech-spectrum noise.
      Vowel identification scores depended upon talker, listening condition, and
      subject type. The relationship between identification errors and spectral details
      of the vowels is discussed.

PMID- 1401513
TI  - Temporal cues for consonant recognition: training, talker generalization, and use
      in evaluation of cochlear implants.
AB  - Limited consonant phonemic information can be conveyed by the temporal
      characteristics of speech. In the two experiments reported here, the effects of
      practice and of multiple talkers on identification of temporal consonant
      information were evaluated. Naturally produced /aCa/disyllables were used to
      create "temporal-only" stimuli having instantaneous amplitudes identical to the
      natural speech stimuli, but flat spectra. Practice improved normal-hearing
      subjects' identification of temporal-only stimuli from a single talker over that
      reported earlier for a different group of unpracticed subjects [J. Acoust. Soc.
      Am. 82, 1152-1161 (1987)]. When the number of talkers was increased to six,
      however, performance was poorer than that observed for one talker, demonstrating
      that subjects had been able to learn the individual stimulus items derived from
      the speech of the single talker. Even after practice, subjects varied greatly in
      their abilities to extract temporal information related to consonant voicing and
      manner. Identification of consonant place was uniformly poor in the multiple
      talker situation, indicating that for these stimuli consonant place is cued via
      spectral information. Comparison of consonant identification by users of multi
      channel cochlear implants showed that the implant users' identification of
      temporal consonant information was largely within the range predicted from the
      normal data. In the instances where the implant users were performing especially
      well, they were identifying consonant place information at levels well beyond
      those predicted by the normal-subject data. Comparison of implant-user
      performance with the temporal-only data reported here can help determine whether
      the speech information available to the implant user consists of entirely
      temporal cues, or is augmented by spectral cues.

PMID- 1401514
TI  - The time course and magnitude of perceptual acclimatization to frequency
      responses: evidence from monaural fitting of hearing aids.
AB  - At high presentation levels, normally aided ears yield better performance for
      speech identification than normally unaided ears, while at low presentation
      levels the converse is true [S. Gatehouse, J. Acoust. Soc. Am. 86, 2103-2106
      (1989)]. To explain this process further, the speech identification abilities of
      four subjects with bilateral symmetric sensorineural hearing impairment were
      investigated following provision of a single hearing aid. Results showed
      significant increases in the benefit from amplifying speech in the aided ear, but
      not in the control ear. In addition, a headphone simulation of the unaided
      condition for the fitted ear shows a decrease in speech identification. The
      benefits from providing a particular frequency spectrum do not emerge
      immediately, but over a time course of at least 6-12 weeks. The findings support
      the existence of perceptual acclimatization effects, and call into question short
      term methods of hearing aid evaluation and selection by comparative speech
      identification tests.

PMID- 1401515
TI  - Vowel perception strategies of normal-hearing subjects and patients using Nucleus
      multichannel and 3M/House cochlear implants.
AB  - Vowel perception strategies were assessed for two "average" and one "star" single
      channel 3M/House and three "average" and one "star" Nucleus 22-channel cochlear
      implant patients and six normal-hearing control subjects. All subjects were
      tested by computer with real and synthetic speech versions of [symbol: see text],
      presented randomly. Duration, fundamental frequency, and first, second, and third
      formant frequency cues to the vowels were the vowels were systematically
      manipulated. Results showed high accuracy for the normal-hearing subjects in all
      conditions but that of the first formant alone. "Average" single-channel patients
      classified only real speech [hVd] syllables differently from synthetic steady
      state syllables. The "star" single-channel patient identified the vowels at much
      better than chance levels, with a results pattern suggesting effective use of
      first formant and duration information. Both "star" and "average" Nucleus users
      showed similar response patterns, performing better than chance in most
      conditions, and identifying the vowels using duration and some frequency
      information from all three formants.

PMID- 1401516
TI  - Effects of short-term auditory deprivation on speech production in adult cochlear
      implant users.
AB  - Speech production parameters of three postlingually deafened adults who use
      cochlear implants were measured: after 24 h of auditory deprivation (which was
      achieved by turning the subject's speech processor off); after turning the speech
      processor back on; and after turning the speech processor off again. The measured
      parameters included vowel acoustics [F1, F2, F0, sound-pressure level (SPL),
      duration and H1-H2, the amplitude difference between the first two spectral
      harmonics, a correlate of breathiness] while reading word lists, and average
      airflow during the reading of passages. Changes in speech processor state (on-to
      off or vice versa) were accompanied by numerous changes in speech production
      parameters. Many changes were in the direction of normalcy, and most were
      consistent with long-term speech production changes in the same subjects
      following activation of the processors of their cochlear implants [Perkell et
      al., J. Acoust. Soc. Am. 91, 2961-2978 (1992)]. Changes in mean airflow were
      always accompanied by H1-H2 (breathiness) changes in the same direction, probably
      due to underlying changes in laryngeal posture. Some parameters (different
      combinations of SPL, F0, H1-H2 and formants for different subjects) showed very
      rapid changes when turning the speech processor on or off. Parameter changes were
      faster and more pronounced, however, when the speech processor was turned on than
      when it was turned off. The picture that emerges from the present study is
      consistent with a dual role for auditory feedback in speech production: long-term
      calibration of articulatory parameters as well as feedback mechanisms with
      relatively short time constants.

PMID- 1401517
TI  - Acoustic and perceptual effects of changes in vocal tract constrictions for
      vowels.
AB  - The purpose of this study was to use vocal tract simulation and synthesis as
      means to determine the acoustic and perceptual effects of changing both the cross
      sectional area and location of vocal tract constrictions for six different
      vowels: Area functions at and near vocal tract constrictions are considered
      critical to the acoustic output and are also the central point of hypotheses
      concerning speech targets. Area functions for the six vowels, [symbol: see text]
      were perturbed by changing the cross-sectional area of the constriction (Ac) and
      the location of the constriction (Xc). Perturbations for Ac were performed for
      different values of Xc, producing several series of acoustic continua for the
      different vowels. Acoustic simulations for the different area functions were made
      using a frequency domain model of the vocal tract. Each simulated vowel was then
      synthesized as a 1-s duration steady-state segment. The phoneme boundaries of the
      perturbed synthesized vowels were determined by formal perception tests. Results
      of the perturbation analyses showed that formants for each of the vowels were
      more sensitive to changes in constriction cross-sectional area than changes in
      constriction location. Vowel perception, however, was highly resistant to both
      types of changes. Results are discussed in terms of articulatory precision and
      constriction-related speech production strategies.

PMID- 1401519
TI  - Target detection, shape discrimination, and signal characteristics of an
      echolocating false killer whale (Pseudorca crassidens).
AB  - This study demonstrated the ability of a false killer whale (Pseudorca
      crassidens) to discriminate between two targets and investigated the parameters
      of the whale's emitted signals for changes related to test conditions. Target
      detection performance comparable to the bottlenose dolphin's (Tursiops truncatus)
      has previously been reported for echolocating false killer whales. No other
      echolocation capabilities have been reported. A false killer whale, naive to
      conditioned echolocation tasks, was initially trained to detect a cylinder in a
      "go/no-go" procedure over ranges of 3 to 8 m. The transition from a detection
      task to a discrimination task was readily achieved by introducing a spherical
      comparison target. Finally, the cylinder was successfully compared to spheres of
      two different sizes and target strengths. Multivariate analyses were used to
      evaluate the parameters of emitted signals. Duncan's multiple range tests showed
      significant decreases (df = 185, p less than 0.05) in both source level and
      bandwidth in the transition from detection to discrimination. Analysis of
      variance revealed a significant decrease in the number of clicks over test
      conditions [F(5.26) = 5.23, p less than 0.0001]. These data suggest that the
      whale relied on cues relevant to target shape as well as target strength, that
      changes in source level and bandwidth were task-related, that the decrease in
      clicks was associated with learning experience, and that Pseudorca's ability to
      discriminate shapes using echolocation may be comparable to that of Tursiops
      truncatus.

PMID- 1401518
TI  - Speech changes following reimplantation from a single-channel to a multichannel
      cochlear implant.
AB  - The speech of a postlingually deafened preadolescent was recorded and analyzed
      while a single-electrode cochlear implant (3M/House) was in operation, on two
      occasions after it failed (1 day and 18 days) and on three occasions after
      stimulation of a multichannel cochlear implant (Nucleus 22) (1 day, 6 months, and
      1 year). Listeners judged 3M/House tokens to be the most normal until the subject
      had one year's experience with the Nucleus device. Spectrograms showed less
      aspiration, better formant definition and longer final frication and closure
      duration post-Nucleus stimulation (6 MO. NUCLEUS and 1 YEAR NUCLEUS) relative to
      the 3M/House and no auditory feedback conditions. Acoustic measurements after
      loss of auditory feedback (1 DAY FAIL and 18 DAYS FAIL) indicated a constriction
      of vowel space. Appropriately higher fundamental frequency for stressed than
      unstressed syllables, an expansion of vowel space and improvement in some aspects
      of production of voicing, manner and place of articulation were noted one year
      post-Nucleus stimulation. Loss of auditory feedback results are related to the
      literature on the effects of postlingual deafness on speech. Nucleus and 3M/House
      effects on speech are discussed in terms of speech production studies of single
      electrode and multichannel patients.

PMID- 1401520
TI  - Avoiding conflicts between the natural behavior of the animal and the demands of
      discrimination experiments.
AB  - Auditory discrimination experiments are traditionally designed without regard for
      ethological or ecological concerns, yet land dwelling mammals may have
      specialized behavior with respect to sound sources. Auditory discriminations
      occur under field conditions, and there is some fit or matching of the animal's
      behavior to the acoustic environment. Understanding this fit requires a knowledge
      of specializations. Understanding the specializations may also guide the design
      of discrimination experiments. This paper reviews a number of auditory
      discrimination experiments that were designed to reveal some of the specialized
      behaviors. These experiments showed the following: (i) The position of a sound
      source is the dominant sensory dimension, over riding the quality of the sound;
      (ii) the effect of reinforcing a response in the presence of a sound is to
      strengthen the response of approaching the source. This effect is ubiquitous in
      discrimination tasks; (iii) sounds that are novel at the start of discrimination
      training more rapidly gain control of responding than sound to which the animal
      has been pre-exposed; (iv) novel low-intensity sounds elicit approach and
      exploration of the source. These behaviors rapidly adapt. These four behavioral
      attributes are considered in terms of their impact upon behavior in the field,
      and of the requirements they impose on the design of experimental
      discriminations.

PMID- 1401521
TI  - Spectral and temporal weights in spectral-shape discrimination.
AB  - The COSS analysis [B. G. Berg, J. Acoust. Soc. Am. 86, 1743-1746 (1989)] was used
      to estimate spectral and temporal weights of a three-component, amplitude
      modulated stimulus in a spectral-shape discrimination task. In all experiments,
      the task of the observer was to detect an increment in the level of the center
      component. A spectral-temporal weight quantifies the relative influence of a
      spectral component on the decisions of an observer during a specified segment of
      the total stimulus duration. In the first two experiments, the signal was added
      to all three temporal segments of the center component. The ideal weights for
      each component should be the same across temporal segments. Spectral-temporal
      weights were obtained for four conditions with different stimulus durations. In
      general, the estimated weights for each component were not equal at different
      temporal segments. In the third experiment, the signal was added to only one of
      three segments of the center component. Ideally, weight patterns should have
      changed when the temporal position of the signal segment was altered. Two
      stimulus durations, 300 and 15 ms, were used. For the 300-ms condition, the
      signal was added to only the end segment, and for all three observers the weight
      patterns are different from that obtained in experiment 1 with the signal added
      to all segments. For the 15-ms conditions, altering the signal position changed
      the estimated weights for only one observer.

PMID- 1401522
TI  - Middle-ear phenomenology: the view from the three windows.
AB  - To provide a common ground for the comparison between theory and experiment, this
      paper presents a framework for the phenomenological description of middle-ear
      mechanics. The framework defines those measurements sufficient to characterize
      the transduction properties of the middle ear and its components.
      Phenomenological equations are represented in the form of an equivalent
      electrical circuit that can be used to deduce testable relations among measurable
      quantities. Two applications are then discussed. First, the classical concept of
      the middle-ear transformer ratio is generalized to include any effects of eardrum
      flexion or nonrotational ossicular motion. Middle-ear models predict that the
      resulting transformer ratios vary considerably with frequency. Second, the
      conditions under which the topology of existing circuit analogs satisfactorily
      approximates middle-ear mechanics are given. Most middle-ear models cannot be
      used to correctly predict the absolute pressures in the cochlea.

PMID- 1401523
TI  - Analyzing reverse middle-ear transmission: noninvasive Gedankenexperiments.
AB  - The phenomenological framework outlined in the companion paper [C. A. Shera and
      G. Zweig, J. Acoust. Soc. Am. 92, 1356-1370 (1992)] characterizes both forward
      and reverse transmission through the middle ear. This paper illustrates its use
      in the analysis of noninvasive measurements of middle-ear and cochlear mechanics.
      A cochlear scattering framework is developed for the analysis of combination-tone
      and other experiments in which acoustic distortion products are used to drive the
      middle ear "in reverse." The framework is illustrated with a simple
      psychophysical Gedankenexperiment analogous to the neurophysiological experiments
      of P. F. Fahey and J. B. Allen [J. Acoust. Soc. Am. 77, 599-612 (1985)].

PMID- 1401524
TI  - An empirical bound on the compressibility of the cochlea.
AB  - Effects of a possible inner-ear compressibility on middle-ear transfer functions
      are explored and a small upper bound on the magnitude of that compressibility
      established. Consequently. the traditional two-port representation of middle-ear
      mechanics remains valid to within a few percent. If the compressibility of the
      cochlea is small but finite, a simple phenomenological model of that
      compressibility correctly predicts hearing thresholds in the "middleless" ear at
      low frequencies. Experiments to establish the value of cochlear compressibility
      and to explore further its possible contributions to residual hearing in patients
      with missing or disarticulated middle-ear ossicles are suggested.

PMID- 1401526
TI  - Determination of sound speed in biological tissues based on frequency analysis of
      pulse response.
AB  - The sound speed in biological tissues provides important diagnostic and treatment
      planning information. Conventional methods of sound-speed determination generally
      require that transducers make physical contact with specimens in order to measure
      thickness and travel time in the time domain. The physical contact may cause
      deformation and affect blood flow and the measurement of travel time in the time
      domain may be sensitive to waveform distortion due to tissue inhomogeneity and
      surface roughness. A method for determination of the sound speed is proposed in
      which the sound travel time in the sample and the difference in total travel time
      from the transducer to the rigid reflector due to the presence of the sample are
      estimated in the frequency domain and which does not require physical contact of
      ultrasonic probes to living or freshly excised tissue specimens. Ultrasonic speed
      measurements in silicone rubber and acrylic resin specimens verified the method
      validity. The standard deviation of the measurements over a 10- x 10-mm area is
      less than 4 m/s. Sound-speed distribution measurements of porcine muscle are in
      agreement with previously published results.

PMID- 1401525
TI  - Temporal structure model of binaural masking level difference.
AB  - It is shown that a simple cross-correlation model is not adequate to explain both
      binaural masking level difference (MLD) and spatial selective attention. The
      reason is that for a low-intensity signal in NoS(pi) condition the maximal
      activity in the binaural analyzer as a function of interaural delay in single
      spectral channel is independent of signal intensity. On the other hand, if
      detection ability is associated with the isolation of tonically firing units, MLD
      is simply explained as the increase in firing synchronization as a function of
      the signal's interaural phase difference (IPD). Quantitatively results are
      presented based on numerical solutions of the model.

PMID- 1401527
TI  - Application of the reverberation-limited form of the sonar equation to dolphin
      echolocation.
AB  - The target detection range of two echolocating Atlantic Bottlenose dolphins as a
      function of target depth in Kaneohe Bay, Hawaii, was determined by Murchison [A.
      E. Murchison, Ph.D. dissertation, Univ. of Calif., Santa Cruz (1980)]. The
      threshold range decreased monotonically as the depth of the 6.35-cm-diam solid
      steel sphere increased and approached the bottom. For the target lying on the
      bottom, the 50% correct detection threshold detection range was approximately 70
      m. The scattering strength of the bottom in Kaneohe Bay at approximately the same
      location of the Murchison's experiment was recently measured using a simulated
      dolphin echolocation signal and a transducer tilted at the appropriate grazing
      angle. The bottom scattering strength along with the target strength of the 6.35
      cm sphere and the dolphin threshold range were incorporated into the generalized
      form of the sonar equation for a reverberation-limited situation and a detection
      threshold of 4.0 dB was calculated. This detection threshold compared well with
      the 2.3 dB obtained in an experiment in which the dolphin was required to detect
      a target in the presence of a clutter screen.

PMID- 1401529
TI  - Modeling phoneme perception. I: Categorical perception.
AB  - On the basis of a number of vowel and stop-consonant discrimination experiments
      (AX and 2IFC fixed and roving) with natural stimuli, it is concluded that stop
      consonant perception is highly categorical: there were few significant
      differences between the discrimination results and the phoneme identification
      results. Moreover, the discrimination and identification response maxima differed
      significantly from the other data points. Vowel perception was much less
      categorical: the maxima in the functions were much less significant, and there
      were significant differences between the various paradigms. Consonant
      discrimination was much less (if at all) subject to range effects than vowel
      discrimination. All these results point to different memory types for stop
      consonants and vowels, and, consequently, to a combination of two different
      theories of speech sound discrimination: dual-process theory (DPT) for
      consonants, and trace-context theory (TCT) for vowels.

PMID- 1401528
TI  - Acoustics and perception of overtone singing.
AB  - Overtone singing, a technique of Asian origin, is a special type of voice
      production resulting in a very pronounced, high and separate tone that can be
      heard over a more or less constant drone. An acoustic analysis is presented of
      the phenomenon and the results are described in terms of the classical theory of
      speech production. The overtone sound may be interpreted as the result of an
      interaction of closely spaced formants. For the lower overtones, these may be the
      first and second formant, separated from the lower harmonics by a nasal pole-zero
      pair, as the result of a nasalized articulation shifting from /c/ to /a/, or, as
      an alternative, the second formant alone, separated from the first formant by the
      nasal pole-zero pair, again as the result of a nasalized articulation around /c/.
      For overtones with a frequency higher than 800 Hz, the overtone sound can be
      explained as a combination of the second and third formant as the result of a
      careful, retroflex, and rounded articulation from /c/, via schwa /e/ to /y/ and
      /i/ for the highest overtones. The results indicate a firm and relatively long
      closure of the glottis during overtone phonation. The corresponding short open
      duration of the glottis introduces a glottal formant that may enhance the
      amplitude of the intended overtone. Perception experiments showed that listeners
      categorized the overtone sounds differently from normally sung vowels, which
      possibly has its basis in an independent perception of the small bandwidth of the
      resonance underlying the overtone. Their verbal judgments were in agreement with
      the presented phonetic-acoustic explanation.

PMID- 1401530
TI  - Modeling phoneme perception. II: A model of stop consonant discrimination.
AB  - Combining elements from two existing theories of speech sound discrimination,
      dual process theory (DPT) and trace context theory (TCT), a new theory, called
      phoneme perception theory, is proposed, consisting of a long-term phoneme memory,
      a context-coding memory, and a trace memory, each with its own time constants.
      This theory is tested by means of stop-consonant discrimination data in which
      interstimulus interval (ISI; values of 100, 300, and 2000 ms) is an important
      variable. It is shown that discrimination in which labeling plays an important
      part (2IFC and AX between category) benefits from increased ISI, whereas
      discrimination in which only sensory traces are compared (AX within category),
      decreases with increasing ISI. The theory is also tested on speech discrimination
      data from the literature in which ISI is a variable [Pisoni, J. Acoust. Soc. Am.
      36, 277-282 (1964); Cowan and Morse, J. Acoust. Soc. Am. 79, 500-507 (1986)]. It
      is concluded that the number of parameters in trace context theory is not
      sufficient to account for most speech-sound discrimination data and that a few
      additional assumptions are needed, such as a form of sublabeling, in which
      subjects encode the quality of a stimulus as a member of a category, and which
      requires processing time.

PMID- 1401531
TI  - Relations among different measures of speech reception in subjects using a
      cochlear implant.
AB  - A comprehensive set of speech reception measures were obtained in a group of
      about 20 postlingually deafened adult users of the Ineraid multichannel cochlear
      implant. The measures included audio, visual, and audiovisual recognition of
      words embedded in two types of sentences (with differing degrees of difficulty)
      and audio-only recognition of isolated monosyllabic words, consonant
      identification (12 alternatives, /Ca/), and vowel identification (8 alternatives,
      /bVt/). For most implantees, the audiovisual gains in the sentence tests were
      very high. Quantitative relations among audio-only scores were assessed using
      power-law transformations suggested by Boothroyd and Nittrouer [J. Acoust. Soc.
      Am. 84, 101-114 (1988)] that can account for the benefit of sentence context (via
      a factor k) and the relation between word and phoneme recognition (via a factor
      j). Across the broad range of performance that existed among the subjects,
      substantial order was observed among measures of speech reception along the
      continuum from recognition of words in sentences, words in isolation, speech
      segments, and the retrieval of underlying phonetic features. Correlations
      exceeded 0.85 among direct and sentence-derived measures of isolated word
      recognition as well as among direct and word-derived measures of segmental
      recognition. Results from a variety of other studies involving presentation of
      limited auditory signals, single-channel and multichannel implants, and tactual
      systems revealed a similar pattern among word recognition, overall consonant
      identification performance, and consonantal feature recruitment. Finally,
      improving the reception of consonantal place cues was identified as key to
      producing the greatest potential gains in speech reception.

PMID- 1401533
TI  - Auditory filter bandwidths in binaural and monaural listening conditions.
AB  - The shape and the effective bandwidth of the auditory filter at 500 Hz was
      examined for binaural and monaural tone-in-noise detection experiments in four
      normal listeners. In the binaural condition, a broadband noise with an interaural
      phase difference of 0 below and an interaural phase difference of pi above a
      certain "edge frequency" was employed to mask a 500-Hz probe tone with an
      interaural phase pi (denoted as No pi S pi). The threshold of the probe tone as a
      function of the edge frequency in this configuration and in a configuration with
      an inverted interaural phase of the masker (denoted as N pi oS pi) was fitted by
      assuming different filter shapes and optimizing their respective parameters. In
      an analogous monaural experiment, the spectral power density of the masker was 15
      dB lower below the "edge frequency" or 15 dB lower above this frequency,
      respectively. Several filter characteristics with two free parameters describe
      the data almost equally well. Their equivalent rectangular bandwidths (ERB) show
      considerably more variations between filter shapes than the 10-dB bandwidth and
      the 90% bandwidth values (i.e., the bandwidths encompassing 90% of the integrated
      area above and below the center frequency). This indicates that either of these
      two bandwidth parameters is more appropriate for comparing auditory filter
      bandwidths than the ERB. For the rounded exponential filter, the 90% bandwidth
      averages to 147 Hz in the binaural and to 125 Hz in the monaural condition. These
      values are up to 12% higher if off-frequency detection is accounted for. Our
      general finding of auditory filter bandwidths in the binaural conditions
      exceeding the monaural bandwidths by approximately 20% may be caused by two
      factors: First, off-frequency detection may be performed in monaural, but not in
      binaural detections tasks and second, the random interaural mismatch in binaural
      noise reduction processes fluctuates slowly and thus modulates and spectrally
      smears the output signal of the binaural noise reduction process.

PMID- 1401532
TI  - A model of the phonatory response time of stutterers and fluent speakers to
      frequency-modulated tones.
AB  - Stutterers and fluent speakers tracked frequency-modulated tones by humming. The
      response time (RT) to the first corrective change in fundamental frequency in
      response to linear ramps of increasing and decreasing frequency was measured. The
      results demonstrate that RT is a function of the stimulus ramp velocity. A model
      of this dependency is provided which consists of parameters of threshold
      frequency and a fixed time delay. The estimated threshold frequency for the
      fluent speakers is 2.029 Hz with 95% confidence interval: (1.70 Hz, 2.35 Hz)
      whereas that of the stutterers is 3.937 Hz (3.28 Hz, 4.60 Hz). These threshold
      frequencies are significantly different (p < 0.0001). This implies that
      stutterers are slower to respond to changes in frequency than are fluent
      speakers. The fixed time delays for the two groups are not significantly
      different. This means that it is possible for the stutterers to respond as fast
      as the fluent speakers (i.e., their basic "reflexes" are the same); however, they
      spend more time in the detection of the change in a tracking signal. This
      supports the model of the stuttered event as being triggered by an instability in
      a multiloop speech motor control system.

PMID- 1401534
TI  - The effects of notched noise on intensity discrimination under forward masking.
AB  - Zeng et al. [Hear. Res. 55, 223-230 (1991)] reported that at moderate levels
      there is an increase in the intensity jnd for 25-ms sinusoidal pedestals
      presented 100 ms after an intense narrow-band noise. They suggested that this
      effect is related to the finding that low spontaneous rate (SR) auditory-nerve
      neurons take a considerable time to recover from adaptation [E. M. Relkin and J.
      R. Doucet, Hear. Res. 55, 215-222 (1991)]: 100 ms after the noise, the low-SR
      neurons still have elevated thresholds. Therefore, the intensity of a pedestal
      falling between the saturation level of the high-SR neurons and the elevated
      threshold of the low-SR neurons will be poorly represented in neutral firing
      rates, and the jnd will be high. A problem with this interpretation is that
      subjects may listen "off frequency." Theoretically, it should always be possible
      to choose a frequency channel for which the pedestal level is within the dynamic
      range of the high-SR neurons. In the present study, the experiment of Zeng et al.
      was replicated but with the pedestal presented in the temporal center of a
      notched noise to prevent off-frequency listening. Surprisingly, the notched noise
      substantially decreased the jnd at mid levels, removing or severely reducing the
      mid-level jnd elevation. This was true for pedestal frequencies of 1 and 6 kHz.
      It was also found that even if the notched noise was terminated before pedestal
      onset the jnd elevation was reduced. This suggests that the effect of the notched
      noise is not due to suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401535
TI  - Discrimination of narrow-band spectra. I: Spectral weights and pitch cues.
AB  - The ability to detect changes in the spectral shape of narrow-band tonal
      complexes (spectral profiles) is examined. The standard consists of three tones
      of equal intensity; thresholds for detecting an increment in the level of the
      central, 1000-Hz tone are estimated. A roving-level procedure is used in order to
      impose a statistical limit on thresholds that can be obtained by basing
      discriminations on absolute intensity. Estimated thresholds are consistently
      below this limit, thus indicating the use of other cues. Generally, thresholds
      are constant for bandwidths ranging from less than a critical band to greater
      than several octaves. Spectral weight estimates, however, are highly dependent on
      bandwidth, providing evidence that the discrimination of narrow-band spectra
      involves different auditory processes than those used to discriminate wideband
      spectra. Additional data show that pitch cues are important within a restricted
      range of intermediate bandwidth, but not for wideband or very narrow-band
      spectra. A version of the EWAIF model involving off-frequency listening is
      proposed to account for the results.

PMID- 1401536
TI  - Asymmetrical discrimination of narrow-band stimuli.
AB  - A three-interval, forced-choice procedure that obtained complete psychometric
      functions was used to study frequency discrimination for 13-item continua of
      impulse-generated, narrow-band, buzz-like, steady-state sounds. For all subjects
      and durations, discrimination relative to the highest center frequency (1060 Hz)
      stimuli was better than discrimination relative to the lowest center frequency
      (940 Hz). This result is not in consonance with traditional reports of pure tone
      frequency discrimination and is not readily explained. However, additional
      experiments with similar stimuli replicated these findings.

PMID- 1401537
TI  - Detection of temporal gaps in sinusoids by elderly subjects with and without
      hearing loss.
AB  - Thresholds for the detection of temporal gaps in sinusoidal signals were measured
      as a function of frequency (100-2000 Hz) and level in 15 elderly hearing-impaired
      subjects and 11 elderly subjects with near-normal hearing at frequencies below
      2000 Hz. The sinusoids were presented in a background noise intended to mask
      spectral splatter associated with the gap. In a separate experiment, auditory
      filter shapes and detection efficiency were estimated for the same subjects using
      the notched-noise method, at center frequencies of 100, 200, 400, and 800 Hz. The
      gap thresholds at higher signal levels were similar for the two groups of
      subjects at all center frequencies tested. The mean gap thresholds were slightly
      higher than those obtained previously from young normally hearing subjects, but
      this was mainly due to the results of a few subjects with large gap thresholds;
      the majority of the elderly subjects had gap thresholds within the normal range.
      Thus reduced temporal resolution does not seem to be an inevitable consequence of
      aging. Gap thresholds at low center frequencies tended to be positively
      correlated with the equivalent rectangular bandwidth (ERB) of the auditory
      filter, the opposite of what would be expected if the auditory filter played a
      role in limiting gap detection. Detection efficiency, as estimated from the
      notched-noise experiment, was poorer for both groups of elderly subjects than for
      young normal listeners, but detection efficiency was not significantly correlated
      with gap thresholds.

PMID- 1401538
TI  - External ear transfer function modeling: a beamforming approach.
AB  - In this article, a beamformer is proposed as a functional model for the spatial
      and temporal filtering characteristics of the external ear. The output of a
      beamformer is a weighted combination of the data received at an array of
      spatially distributed sensors. The beamformer weights and array geometry
      determine its spatial and temporal filtering characteristics. A procedure is
      described for choosing the weights to minimize the mean-squared error between the
      beamformer response and the measured response of the external ear. The
      effectiveness of the model is demonstrated by designing a beamformer of several
      hundred weights that duplicates and interpolates the measured external ear
      response of a cat over broad ranges of frequency and direction. A limited
      investigation of modeling performance as a function of array geometry is
      reported.

PMID- 1401539
TI  - The effect of olivocochlear bundle transection on tuning curves and acoustic
      distortion products.
AB  - A growing body of research suggests that the efferent innervation to the cochlea,
      the olivocochlear bundle (OCB), may modulate the mechanical function of the
      cochlea. However, the role of tonic OCB input in cochlear function remains poorly
      understood. The purpose of this study was to determine the influence of tonic
      efferent input on cochlear mechanics, by transecting the entire OCB in guinea
      pigs, and observing changes in tuning curves and acoustic distortion products.
      The OCB was transected by avulsing the inferior vestibular nerve as it enters the
      internal auditory canal of the right bulla. Auditory brainstem response (ABR)
      thresholds, ABR tuning curves, and acoustic distortion products were measured
      before and after surgery. Successful transection of the OCB was verified
      histochemically. Results revealed no consistent changes in tuning curves or in
      the growth functions of the distortion products. To the extent that these
      measures reflect cochlear mechanical nonlinearities, it is concluded that tonic
      OCB input is not necessary for grossly normal cochlear mechanical function in the
      10-kHz region of the guinea pig cochlea. It thus seems unlikely that the
      efferents are involved in establishing a "set point" for cochlear operation.

PMID- 1401541
TI  - Program of the 124th meeting of the Acoustical Society of America. New Orleans,
      Louisiana, 31 October-4 November 1992. Abstracts.

PMID- 1401540
TI  - Directional dependence of auditory sensitivity and frequency selectivity in the
      leopard frog.
AB  - Direction-dependent changes in frequency selectivity were documented in three
      populations of neurons in the auditory periphery of the leopard frog: low-, mid-,
      and high-frequency sensitive fibers. These changes were most pronounced in the
      mid-frequency (720-1199 Hz) sensitive fibers which exhibited positive shifts in
      characteristic frequencies (CFs) and concomitant narrowed bandwidths from
      posterior speaker presentations. Maximum sensitivities were observed for
      ipsilateral speaker presentations in these fibers. Low-frequency (63-500 Hz)
      sensitive fibers exhibited mean threshold shifts at their CFs of up to -7 dB with
      posterior speaker presentations. Low- and high-frequency sensitive fibers whose
      CFs closely correspond to the peaks of spectral energy of the species' mating
      call were the most sensitive (exhibited lowest thresholds) but showed little
      directional-dependent frequency selectivity. Directional-dependent variation in
      frequency selectivity and sensitivity in low- and mid-frequency sensitive fibers
      was attributed to pressure and phase differences impinging on the inner surface
      of the eardrum.

PMID- 1401542
TI  - Controversies in nursing ethics: a historical review.
AB  - The author critiques the dialectic between justice-based ethics and an ethic of
      caring from a historical perspective (by analogy with the dialectic between agape
      and friendship). Justice-based ethics have been problematic for nursing because
      of the decontextualized approach. The ethic of caring is problematic because
      caring, being contextual, is particularistic and therefore can be based on
      morally irrelevant factors, such as liking. There is a tradition of writing which
      seeks to reconcile the particularistic obligations of friendship with the moral
      duty to all others equally. Ideas from the following authors are reviewed for
      relevance to nursing: Aristotle, Aelred of Rievaulx, Augustine, John Cassian,
      Cicero, George Berkeley, Immanuel Kant, Michel de Montaigne, Jeremy Taylor and
      Max Weber. The authors concludes by noting that both sides of the dialectic are
      synthesized in the lived experience of individuals. A synthesis in thought is
      called for on this basis.

PMID- 1401543
TI  - Ethical reasoning in nurses' and physicians' stories about care episodes.
AB  - Twenty-three registered nurses and nine physicians reported 43 stories about
      ethically difficult care situations. Themes in nurses' and physicians' stories
      were described by means of narrative ethical theory. It turned out that nurses
      and physicians related different kinds of stories. They also seemed to use
      different kinds of ethical reasoning. This result was interpreted as mainly
      connected to the fact that the two professions have different tasks to accomplish
      and are trained in disciplines with different foci; nursing and medicine. The
      need to find a common frame story covering the two professional stories was
      stressed.

PMID- 1401544
TI  - Ethical challenge in community health nursing.
AB  - Community health nurses frequently face situations involving ethical conflicts,
      but little research has been carried out in this area. This paper, based on a
      study of dilemmas defined by 30 practising community health nurses in urban and
      rural British Columbia, Canada, presents an analysis of the situations that
      contain the most serious ethical conflicts for nurses working in the community.
      Although issues related to client's rights, nurses' interactions with colleagues
      and the system, and nurses' rights were explored, nurses in the study reported
      that situations involving high-risk parenting provided the most serious ethical
      challenges. Strategies to help nurses caring for such vulnerable clients are
      described. As well, this paper offers some discussion on implications for
      community health nursing practice and education in light of current changes and
      challenges.

PMID- 1401545
TI  - From helper to human: a reconceptualization of the nurse as person.
AB  - This paper explores the nature of the nurse as person, as represented by nursing
      literature and in the author's own research, by considering the tendency nurses
      have to perceive as different the characteristics of nurses and patients as human
      beings. Nursing scholars have tended to categorize nurses and patients into
      discrete 'compartments' that are convenient for descriptive purposes, but
      nevertheless have had a tendency to limit people's essential humanness. The
      metaparadigm concept of person in nursing can take on a different meaning if
      people are regarded in terms of their oneness, rather than by their separateness.
      A brief introduction will be given to some meanings generated in some nursing
      research, which described the effects of ordinariness as they were manifested by
      nurses and patients in everyday nursing unit life. The possibility is raised that
      a reconceptualization of the nurse could describe the nurse, not only as a
      professional helper, but also as a human, whose effectiveness is enhanced through
      a sense of shared humanity with patients.

PMID- 1401546
TI  - Reducing distress during abortion: a test of sensory information.
AB  - The purpose of this study was to examine the effect of providing sensory
      information on distress during first-trimester abortion using a 2 x 2 factorial
      design. The factors were type of information given and type of anaesthesia used.
      Eighty-four women completed pre-abortion measures of state anxiety, and
      subjective pain and distress. Post-abortion measures included behavioural
      distress, subjective distress, pain and state anxiety. No significant differences
      were found for type of information (sensory vs. general) received on subjective
      or behavioural distress measures. Women receiving intravenous sedation together
      with local cervical block reported less subjective distress and pain than women
      receiving local anaesthesia alone. Sensory information was not effective in
      reducing distress during abortion.

PMID- 1401547
TI  - Stress, alcohol, tobacco and illicit drug use amongst nurses: a Scottish study.
AB  - This paper examines levels of stress amongst a representative sample of 600
      qualified nurses in the Lothian Region of Scotland. The results indicated a
      number of significant variations in the patterns of stress amongst different
      subgroups of nurses. The highest stress levels amongst females were evident
      amongst medical nurses while the lowest levels were reported by those in
      psychiatry. No comparable differences were evident amongst males in different
      fields of nursing. Stress was also associated with the use of alcohol, but not
      with tobacco smoking. Illicit drug use was associated with stress amongst
      females. Amongst both males and females the variable most predictive of stress
      was concern about AIDS. Amongst females, administrative workload was an equally
      important predictor. It is concluded that as the HIV/AIDS epidemic spreads
      efforts will be needed to support nursing staff and to reduce stress levels.

PMID- 1401548
TI  - Acquired immunodeficiency syndrome: knowledge and attitudes of nurses in Northern
      Ireland.
AB  - The number of people suffering from conditions associated with HIV infection is
      growing steadily. These people require care from nurses who should be well
      trained to undertake all the various aspects of nursing care. Surveys have
      indicated that health professionals associate AIDS with minority groups such as
      homosexuals, drug-abusers and prostitutes. Incidents of sub-optimal nursing care
      of AIDS patients, or suspected AIDS patients belonging to these minority groups,
      have been well documented. Surveys have revealed much ignorance and confusion
      among the general public as well as among health professionals with regard to
      this controversial syndrome. This study aimed to measure nurses' knowledge and
      attitudes towards homosexuals, drug-abusers and prostitutes, who through their
      lifestyle are at increased risk for HIV infection. Questionnaires were
      distributed to a random sample of 800 nurses in Northern Ireland. The sample was
      stratified by several demographic variables. A response rate of almost 60% was
      achieved. Nurses appeared to have a moderate knowledge of issues related to HIV
      infection, but there were large gaps in their knowledge of the terminology used
      in HIV infection. Nurses were not extremely worried about AIDS itself. However,
      homosexuals, prostitutes and drug-abusers were seen to be at least partly
      responsible for their own illness. Implications for nursing care and for nurse
      education are discussed.

PMID- 1401549
TI  - Caring in the preparation of long-term psychiatric patients for non-institutional
      care: ethnonursing study.
AB  - Caring is the central and unifying domain for the body of knowledge and practices
      in nursing. It was the purpose of this ethnonursing study to describe caring in
      the residential training for long-term psychiatric patients in Finland in 1977
      1988. Data were collected by interviewing 20 patients and 11 members of staff. On
      the basis of the empirical data, four stages of caring could be distinguished:
      formation, reformation, fragmentation and reintegration. The changes in caring
      occurred on the following dimensions: work for wages vs. vocation; spontaneous
      social interaction vs. the systematic instruction of practical skills; and
      collective activities vs. individual activities.

PMID- 1401550
TI  - On laying the foundations for an empirico-logical model of mental health nursing.
AB  - This paper argues that nursing is an elemental activity, the first concern of
      which is a person's experience of illness, not the causes of that experience. Any
      model of nursing should begin with an account of that experience and deduce from
      that what it is that nurses ought to do in order to explain what it is that they
      actually do. The logical form of such a model is delineated. An account of the
      experience of illness is offered and the nursing imperatives implied by such an
      account are stated in terms of securing client safety, obviating the client's
      experience by treatment and motivating the client to sustain or resume ordinary
      activities of life. These dimensions of nursing care--safety, treatment and
      motivation--were tested against the actual activities of mental health nurses in
      three services and were found to have utility as categories of nursing activity.
      A summary of that research is given and an outline of a model of mental health
      nursing suggested by the results is given.

PMID- 1401551
TI  - Case management in community care: concepts, practices and implications for
      nursing.
AB  - Case management has recently become a prominent issue in British community policy
      and practice, but one which, at the same time, has been subjected to a variety of
      interpretations. For this reason, it is considered useful to analyse it in terms
      of a framework embracing conceptual and operational components rather than within
      the more limiting confines of conventional definitions. A review, within this
      framework, of initial research projects suggests case management to be a viable
      mode of community care, with generally favourable outcomes. It also suggests a
      potentially significant role for community nurses as case managers, although
      several issues need to be considered when implementing these practices. Finally,
      a number of questions emerge which should be the focus of future research in the
      area.

PMID- 1401552
TI  - Long-term care personnel assess their attitudes and knowledge of the older adult.
AB  - The purpose of this study was to compare long-term care employees' attitude and
      knowledge about myths of ageing and normal age changes, before and after exposure
      to formal educational sessions. The researchers investigated if there was a
      difference in knowledge level and change in attitudes of long-term care employees
      after educational sessions. The subjects for this study were defined as persons
      who had any contact with the residents at St Charles Care Center. The final data
      set used in the analysis contained 84 observations. Each participant attended
      three 1-hour classes which consisted of simulation of handicaps, normal age
      related changes, and myths and realities of ageing. Overall, there was a
      significant increase in knowledge from the pre-test to the post-test. The study
      also tested for a negative (anti-aged) bias attitude and a positive (falsely pro
      aged) bias attitude among the individuals. At the end of the study there was
      still a slight negative biased attitude towards ageing. The data suggest that
      continuing education is an effective means of influencing the knowledge and
      attitudes of personnel in long-term care facilities. Recommendation for future
      research should be that this study be replicated in another long-term care
      facility with the addition of a job satisfaction tool.

PMID- 1401553
TI  - Life history: a qualitative method of research.
AB  - The life-history method of qualitative research is an alternative to empirical
      methods for identifying and documenting health patterns of individuals and
      groups. It allows the nurse researcher to explore a person's microhistorical
      (individual) experiences within a macrohistorical (history of the time)
      framework. Life-history information challenges the nurse to understand an
      individual's current attitudes and behaviours and how they may have been
      influenced by initial decisions made at another time and in another place. This
      paper describes a new direction in nursing research and identifies specific steps
      for using the life-history approach.

PMID- 1401554
TI  - Continuing professional education for qualified nurses: a review of the
      literature.
AB  - Reviewed literature identifies the importance of continuing professional
      education and professional development for nurses subsequent to initial
      registration (including enrolled nurses). However, there is a lack of empirically
      based work analysing nurses' perceptions of their continuing professional
      education needs and the perceived outcomes of continuing professional education
      in terms of changes in knowledge accretion, attitudes, skills, job satisfaction,
      staff retention and career development. It is suggested that this lack of
      empirical work needs to be addressed if the proposed plans of the United Kingdom
      Council for Nursing, Midwifery and Health Visiting (UKCC) to introduce mandatory
      continuing professional education are to have maximum benefits for clients,
      nurses and the service.

PMID- 1401555
TI  - The perception of time as a factor in Rogers' Science of Unitary Human Beings: a
      literature review.
AB  - This literature review examines an operationalization of Martha Rogers' Science
      of Unitary Human Beings. The principle of helicy and the theory of accelerating
      evolution has been used by a number of authors as a theoretical framework for the
      exploration of how patients, particularly those who are elderly, perceive the
      passage of time. Although there is no conclusive evidence to support the aspect
      of Rogers' theory of accelerating evolution that suggests that as people grow
      older they perceive time as passing more quickly, there is evidence that suggests
      that different elderly patients can have a variable perception of the passage of
      time. For example, some patients perceive the passage of time as rapid and will
      be happy to sit quietly. Others may perceive the passage of time as occurring
      more slowly and will require diversional therapy. A conclusion is reached that
      nurses should include individual assessments of the patients' perception of the
      passage of time in order to identify accurately the degree of need for
      diversional activities.

PMID- 1401556
TI  - Leininger's Culture Care Theory of Nursing.

PMID- 1401557
TI  - Pioneering nursing research.

PMID- 1401558
TI  - Global issues for nurses and nursing.

PMID- 1401559
TI  - The Safe Medical Device Act of 1990--ethical dilemmas for nurses.

PMID- 1401560
TI  - Education. From diversity to enrichment.

PMID- 1401561
TI  - The end of history.

PMID- 1401562
TI  - Nursing faculty practice: an organizational perspective.
AB  - After reviewing the faculty practice literature of the 1980s and finding
      philosophical support for practice but also growing concerns about faculty role
      overload, the authors report a study to identify organizational factors that
      influence the role expectations of faculty members about practice. A survey was
      sent to the deans or directors of all National League for Nursing--accredited
      baccalaureate nursing programs (n = 462). Of the 356 respondents (78 per cent),
      224 (63.3 per cent) reported that their school had practicing faculty, but only
      20 schools (8.8 per cent) required practice. Written faculty practice plans were
      reported by 23 schools (10.2 per cent), and nursing centers by 41 schools. Thirty
      six respondents (16 per cent) reported that practicing faculty generated revenue
      for the school. Practice was required for promotion in 15.8 per cent and for
      tenure in 15.3 per cent of all schools surveyed. The study showed significant
      direct relationships between master's and doctoral programs and practicing
      faculty, but there was an inverse relationship between the presence of a health
      science center and schools with practicing faculty. Organizational factors
      relating to both the number and per cent of faculty who practiced included
      requiring practice, having a practice plan, and having practice as a criterion
      for promotion and for tenure. Revenue generation and presence of formalized
      practice arrangements were related to the number of faculty who practiced but not
      the per cent of the total faculty who practiced. The study's findings have
      implications for nursing education in designing organizational structures and
      rewards that support faculty practice.

PMID- 1401563
TI  - Faculty research productivity and organizational structure in schools of nursing.
AB  - The purpose of this study was to identify the relationship between faculty
      research productivity and organizational structure in schools of nursing. The
      need for nursing research has been widely recognized by members of the nursing
      profession, yet comparatively few engage in conducting research. Although
      contextual variables have been investigated that facilitate or inhibit nursing
      research, the relationship between organizational structure and nursing research
      productivity has not been examined. This problem was examined within the context
      of the Entrepreneurial Theory of Formal Organizations. A survey methodology was
      used for data collection. Data on individual faculty research productivity and
      organizational structure in the school of nursing were obtained through the use
      of a questionnaire. A random sample of 300 faculty teaching in 60 master's and
      doctoral nursing schools in the United States was used. The instruments for data
      collection were Wakefield-Fisher's Adapted Scholarly Productivity Index and
      Hall's Organizational Inventory. The data were analyzed using Pearson Product
      Moment Correlation Coefficients and multiple correlation/regression techniques.
      The overall relationship between faculty research productivity and organizational
      structure in schools of nursing was not significant at the .002 level of
      confidence. Although statistically significant relationships were not identified,
      scholarly research productivity and its subscale prepublication and research
      activities tended to vary positively with procedural specifications in a highly
      bureaucratic organizational structure. Further research may focus on
      identification of structural variables that support highly productive nurse
      researchers.

PMID- 1401564
TI  - Nursing theory in nursing education: an educational imperative.
AB  - Nursing has accepted theory as basic to its practice; however, the use and
      development of nursing theory is constrained by the approach used in nursing
      education. It is not appropriate or sufficient to isolate theory in one course.
      Moreover, confining nursing theory courses to graduate curricula, which is the
      custom in many schools of nursing, suggests that to focus on theory in the
      profession is esoteric. These curricular approaches inhibit socialization of
      students to the value of theory as essential to practice. It is imperative that
      nursing education engage students in theory-related content at all levels. This
      article presents a scheme to achieve systematic integration of theory-related
      content in curricula at all levels of nursing education from associate degree to
      doctorate. Through theory-based practice, nursing will come to realize its full
      potential as a discipline.

PMID- 1401565
TI  - Liberal and professional undergraduate nursing education: maintaining the
      connections.
AB  - Current recommendations to improve undergraduate education range from increasing
      the proportion of general education credits to removing professional preparation
      from undergraduate education. The authors argue for the necessity of integrating
      general education and professional preparation throughout all levels of higher
      education. A conceptual framework to study professional preparation developed by
      Stark et al. is presented. Methods to integrate both general education and
      professional preparation are analyzed, and specific implications for nursing are
      discussed.

PMID- 1401566
TI  - Distance learning: an innovative approach to nursing education.
AB  - This article presents four views encompassing one nursing department's experience
      using distance learning technology. The challenge of presenting a nursing class
      through distance technology is discussed from the perspective of the
      telecommunication faculty providing the technological support, the nursing
      faculty teaching the on-campus course, the off-campus nursing faculty
      coordinating the course at the outreach site, and the head of the Department of
      Nursing. Review of course grades demonstrated that off-campus students achieved
      higher grades than on-campus students. All students evaluated the teacher as
      being effective; however, off-campus students were not as strong in their
      opinion.

PMID- 1401568
TI  - Nursing diagnoses: a study of cultural relevance.
AB  - This study examines the adequacy/inadequacy of three nursing diagnoses with
      cultural etiologies: (1) impaired verbal communication related to cultural
      differences; (2) impaired social interaction related to sociocultural dissonance;
      and (3) noncompliance related to patient value system. The research tool was
      administered to the membership of the American Nurses Association Council on
      Cultural Diversity and the International Transcultural Nursing Society, with a
      response rate of N = 245 (42.2 per cent) from 43 states, the District of
      Columbia, and seven foreign countries. The tool listed the North American Nursing
      Diagnosis Association (NANDA) defining characteristics and cultural etiology for
      each diagnosis rated on a five-point Likert scale from "nearly always present" to
      "rarely present." The subjects also wrote and ranked other defining
      characteristics they used to make the diagnosis in clinical practice. Percentage
      distribution results indicate no defining characteristic meets the NANDA criteria
      for a major or minor defining characteristic. By collapsing categories, seven
      were acceptable only as minor defining characteristics. Respondents' 113
      suggestions for additional characteristics were content analyzed. Themes for 12
      categories were intuited and added to the lists. Based on respondents'
      suggestions, the definitions for each diagnosis were reworked, and new cultural
      related factors were added. The cultural adequacy/inadequacy of elements within
      these three diagnoses was identified and provides the opportunity for greater
      selectivity in their clinical use. Additional suggestions from transcultural
      nursing experts form a data base for future research to expand the use of the
      currently limited components of NANDA diagnoses with culturally diverse patients.

PMID- 1401567
TI  - Preparing clinical preceptors to teach master's-level students in oncology
      nursing.
AB  - This article reports the development of a structured program for clinical nurse
      specialists who served as clinical preceptors for graduate students in an
      oncology nursing program. A needs assessment of clinical preceptors was
      completed, and a program for the preceptors was developed based on the learning
      needs identified. In addition to the program, a Manual for Clinical Preceptors
      was developed. The benefits of this program include networking; positive working
      relationships among the preceptors, faculty, and students; potential job
      opportunities for students; potential applicants from the clinical agencies; and,
      ultimately, improved care for patients with cancer and their families. The
      authors conclude that administrators should support efforts to nurture and
      recognize the personnel in the clinical agencies.

PMID- 1401569
TI  - Empowering the new graduate: a renewed professionalism for nursing.
AB  - We are facing a crisis in nursing not unlike that faced by our foremothers and
      forefathers: a shortage of nurses that promises to get worse before it gets
      better. Attrition contributes to this shortage as does competition from other
      professions. Empowering our graduates is one solution to the crisis. Empowerment
      will enable us to retain persons in the profession as well as to attract new
      members. Providing graduates with a sense of the caring and scholarly heritage of
      the profession is part of that empowerment.

PMID- 1401570
TI  - Dental education policy: changing factors.

PMID- 1401571
TI  - The future of prevention in dental schools.

PMID- 1401572
TI  - The role of public health in academic dentistry and the role of dentistry (oral
      health) in academic public health.

PMID- 1401573
TI  - Senior student general dentistry program: an alumni assessment.

PMID- 1401574
TI  - Dentistry in the 90's.

PMID- 1401576
TI  - Reciprocity and licensure by credentials--European style.

PMID- 1401575
TI  - The continuing education of professional ethics in dentistry.

PMID- 1401577
TI  - Appropriateness of care. Appropriateness of restorative treatment
      recommendations: a case for practice-based outcomes research.

PMID- 1401578
TI  - The ethical issues of fluoridation.

PMID- 1401579
TI  - Policy options for fluoride use.

PMID- 1401580
TI  - Fluoridation in the 1990's.

PMID- 1401581
TI  - Fluoride: benefits and risks of exposure. The preparation of a report.

PMID- 1401582
TI  - Fluoridation: legal and political issues.

PMID- 1401583
TI  - Managing TMD.

PMID- 1401584
TI  - Periodontal prosthesis: creating successful restorations.
AB  - When the dentition is mutilated by periodontal disease, it's hard to restore. The
      authors outline the mechanical and biological problems to overcome in treating
      advanced periodontal disease.

PMID- 1401585
TI  - Symptom not a diagnosis.

PMID- 1401586
TI  - Things your most satisfied patients won't tell you.
AB  - In a competitive market, patient satisfaction is critical. The author surveyed
      patients and discusses several nontechnical factors that influence patient
      satisfaction.

PMID- 1401587
TI  - Questionable surgery.

PMID- 1401588
TI  - An infectious disease.

PMID- 1401589
TI  - Fast-acting sterilant under study.

PMID- 1401590
TI  - Orthodontic device adapted to help disabled children.

PMID- 1401591
TI  - Recent advances in periodontal diagnosis and treatment: exploring new treatment
      alternatives.
AB  - A better understanding of the etiology and pathogenesis of periodontal diseases
      provides clinicians and researchers with a number of new diagnostic techniques
      and treatment alternatives. These new developments may also offer the clinician
      additional information for treatment planning.

PMID- 1401592
TI  - Sterilizing dental handpieces.

PMID- 1401594
TI  - VA oral HIV surveillance program: understanding the disease.

PMID- 1401593
TI  - Major psychological disorders in chronic TMD patients: implications for
      successful management.
AB  - The authors assessed psychological disorders in 50 chronic TMD patients. These
      disorders appear to be a major concomitant factor in chronic TMD, and may need to
      be treated for successful outcomes.

PMID- 1401595
TI  - Today's sonics: using the combined hand/sonic endodontic technique.
AB  - Combing sonic technology with hand instrumentation facilitates root canal
      preparation. The authors present an efficient and safe technique.

PMID- 1401596
TI  - It's not over yet!

PMID- 1401597
TI  - Oral mucosal ulcers: diagnosis and management.

PMID- 1401598
TI  - Minocycline use discolors teeth.
AB  - A 25-year-old woman with gray striated staining on all teeth took minocycline for
      two years. Staining corresponded with the treatment time.

PMID- 1401599
TI  - Replanting avulsed primary teeth.
AB  - Tooth replantation is a viable procedure if performed under the following
      acceptable guidelines: Replant the tooth if time lapse is less than 30 minutes (a
      time lapse of more than one to two hours results in a poor prognosis); Transport
      the tooth or teeth in milk, saliva or blood; and Keep teeth and replant area
      clean to minimize infection. Quick action by the mother in bringing the child to
      the hospital emergency room was a vital first step. The fact that the child held
      the teeth in her mouth en route to the hospital--bathed in saliva and blood,
      still attached by the bit of gingival tissue in the warm mouth's environment-
      helped to contribute to a positive situation as well as did the good home care.

PMID- 1401600
TI  - Oral health activities of U.S. children: results of a national health interview
      survey.
AB  - Data from the 1989 National Health Interview Survey show oral health activities
      for U.S. children aged 2-17. Key population subgroups neither received optimal
      preventive care nor visited a dentist regularly.

PMID- 1401601
TI  - Modifiers of timing and possible triggers of acute myocardial infarction in the
      Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group.
AB  - OBJECTIVES: The aim of this study was to provide insight into the mechanism of
      acute myocardial infarction by determining the modifiers of timing and possible
      triggers of onset of infarction. BACKGROUND: A higher frequency of onset of acute
      myocardial infarction has been reported in the morning with a peak in the 1st 3 h
      after awakening. This observation suggests that the onset of infarction may be
      triggered by activity in the morning and at other times of the day. METHODS: The
      clinical history of the 3,339 patients entered into the Thrombolysis in
      Myocardial Infarction phase II study was analyzed to determine characteristics
      predicting a higher frequency of infarction between 6 AM and noon, and onset of
      infarction during exertion. RESULTS: A higher proportion (34.4%) of infarctions
      began in the morning (6 AM to noon) compared with other times of the day.
      Characteristics independently predicting a higher frequency between 6 AM to noon
      were no beta-adrenergic blocking agent use in the 24 h before infarction, no
      discomfort other than the index pain in the preceding 48 h, occurrence of the
      infarction on a weekday and no history of current smoking. In 18.7% of patients,
      infarction occurred during moderate or marked physical activity. Independent
      predictors of exertion-related infarction included male gender, no history of
      current smoking, white race, no use of calcium channel blocking agents or
      nitrates in the preceding 24 h, the absence of either chest pain at rest in the 3
      weeks before infarction or any pain in the preceding 48 h, the absence of new
      onset angina and the presence of exertional pain in the preceding 3 weeks.
      Compared with patients whose infarction occurred at rest or during mild activity,
      those with exertion-related infarction had fewer coronary vessels with > or = 60%
      stenosis (p = 0.002) and were more likely to have an occluded infarct-related
      vessel after thrombolytic therapy (p = 0.01). CONCLUSIONS: Further study of the
      timing and activity at onset of infarction may provide insight into the
      pathophysiologic mechanisms causing acute myocardial infarction and provide clues
      to preventive measures.

PMID- 1401602
TI  - Effect of amiodarone on mortality after myocardial infarction: a double-blind,
      placebo-controlled, pilot study.
AB  - OBJECTIVES: The goal of this study was to evaluate the effect of amiodarone on
      mortality, ventricular arrhythmias and clinical complications in high risk
      postinfarction patients. BACKGROUND: No therapy has been shown to reduce sudden
      death in patients ineligible to receive beta-adrenergic blocking agents after
      myocardial infarction. METHODS: Patients who were not eligible to receive beta
      blockers were randomized to receive amiodarone (n = 305) or placebo (n = 308) for
      1 year. RESULTS: There were 21 deaths in the amiodarone group compared with 33 in
      the placebo group (odds ratio 0.62, 95% confidence interval [CI] 0.35 to 1.08, p
      = 0.095). There were two noncardiac deaths in the amiodarone group and none in
      the placebo group; thus, the difference in cardiac mortality (19 vs. 33,
      respectively) was statistically significant (odds ratio 0.55, 95% CI 0.32 to
      0.99, p = 0.048). There was a significant decrease in Lown class 4 ventricular
      arrhythmias (7.5% vs. 19.7%, respectively, p < 0.001). Adverse effects developed
      in 30% of amiodarone-treated patients and 10% of placebo-treated patients.
      Pulmonary toxicity, which was mild and reversible, occurred in only one patient
      in the amiodarone group but in no patient in the placebo group. CONCLUSIONS: This
      trial demonstrated a significant reduction in cardiac mortality and ventricular
      arrhythmias with amiodarone treatment. However, given the wide confidence
      intervals and borderline statistical significance of our trial, larger trials are
      needed to confirm or refute this view.

PMID- 1401603
TI  - The amiodarone odyssey.

PMID- 1401604
TI  - Benefits of intraoperative echocardiography in the surgical management of
      hypertrophic cardiomyopathy.
AB  - OBJECTIVES: The purpose of this study was to determine the role of intraoperative
      echocardiography in planning the site and extent of myectomy and in ensuring
      adequate control of the left ventricular outflow tract gradient. BACKGROUND:
      Although intraoperative echocardiography has been found to be beneficial in
      patients undergoing valve repair, its impact on surgical decisions in patients
      undergoing septal myectomy for hypertrophic cardiomyopathy has not been
      described. METHODS: In 50 patients undergoing septal myectomy over a 5-year
      period, epicardial echocardiography was performed before cardiopulmonary bypass
      to establish the extent of outflow tract obstruction, locate its site and plan
      the myectomy. In 30 patients, transesophageal echocardiography was also used to
      corroborate data on outflow tract anatomy and examine the mitral valve. RESULTS:
      In 40 patients (80%) the initial myectomy resulted in a reduction of the maximal
      outflow tract gradient from 88 +/- 45 to 24 +/- 11 mm Hg, measured by epicardial
      continuous wave Doppler echocardiography. Ten patients (20%) were shown by
      postbypass intraoperative echocardiography to have an unsatisfactory result,
      based on a persistent gradient > 50 mm Hg (n = 7) or persistent mitral
      regurgitation of greater than moderate severity (n = 3). The postbypass two
      dimensional echocardiogram was then used to direct the surgeon toward the most
      likely site of continued obstruction, and cardiopulmonary bypass was reinstituted
      to permit further myectomy (n = 9) or mitral valve repair (n = 1). After the
      second or subsequent period of cardiopulmonary bypass, the outflow tract gradient
      (26 +/- 14 mm Hg) was substantially reduced and was not significantly different
      from the postbypass gradient (24 +/- 11 mm Hg) in the group with initial surgical
      success. At postoperative follow-up (20 +/- 37 weeks), the maximal measured
      outflow tract gradient (22 +/- 21 mm Hg) showed no difference between patients
      with immediate surgical success and those requiring a second period of
      cardiopulmonary bypass for further resection. CONCLUSIONS: Intraoperative
      echocardiography proved a useful tool to guide the site and extent of septal
      myectomy, leading to more adequate surgical resection and to persistence of
      satisfactory control of the outflow tract obstruction into the early follow-up
      period.

PMID- 1401605
TI  - Effect of progression of left ventricular hypertrophy on coronary artery
      dimensions in aortic valve disease.
AB  - OBJECTIVES: The effect of progression of left ventricular hypertrophy on coronary
      artery dimensions was studied in patients with aortic valve disease. METHODS:
      Cross-sectional area of the left and right coronary arteries was determined by
      quantitative coronary arteriography in 12 control subjects and in 10 patients
      with aortic valve disease at baseline and after a follow-up period of 66 months.
      RESULTS: The cross-sectional area of the left coronary artery was larger in
      patients with aortic valve disease than in control subjects (left anterior
      descending artery 13 vs. 8 mm2, p < 0.001; left circumflex artery 13 vs. 6 mm2, p
      < 0.001). At the follow-up examination, cross-sectional area of the left coronary
      artery increased (left anterior descending artery 17 mm2, p < 0.01 vs. baseline;
      left circumflex artery 15 mm2, p < 0.01 vs. baseline). The cross-sectional area
      of the right coronary artery was not different in patients with aortic valve
      disease from that in control subjects. Left ventricular muscle mass was larger in
      patients with aortic valve disease both at baseline (269 g, p < 0.001) and after
      follow-up examination (339 g, p < 0.001) than in control subjects (136 g). The
      appropriateness of coronary artery size with respect to muscle mass was evaluated
      by normalizing cross-sectional area of the left coronary artery (left anterior
      descending plus left circumflex artery) per 100 g of left ventricular muscle mass
      (mm2/100 g). This index was 10.9 mm2/100 g in control subjects, and decreased in
      subjects with aortic valve disease from 10.3 mm2/100 g at baseline to 8.6 mm2/100
      g at the follow-up measurement (p < 0.05 vs. control values). CONCLUSIONS: In
      patients with aortic valve disease, the progression of left ventricular
      hypertrophy is associated with an increase in left anterior descending and left
      circumflex coronary artery dimensions, whereas the size of the right coronary
      artery remains unchanged. Despite the enlargement of the left coronary artery,
      the cross-sectional area of the left coronary artery per 100 g of left
      ventricular muscle mass decreased. Hence, the increase in coronary artery size
      appears to be inadequate when the severity of left ventricular hypertrophy
      increases.

PMID- 1401606
TI  - Progressive inadequacy of vascular support in myocardial hypertrophy.

PMID- 1401607
TI  - Left ventricular relaxation in dilated cardiomyopathy: relation to loading
      conditions and regional nonuniformity.
AB  - OBJECTIVES: The purpose of the present study was to investigate how loading
      conditions and regional nonuniformity affect left ventricular relaxation in
      dilated cardiomyopathy. BACKGROUND: Left ventricular relaxation is impaired in
      dilated cardiomyopathy. It has been suggested that relaxation abnormality is
      related to loading conditions and regional nonuniformity in the diseased heart.
      METHODS: Left ventriculography with simultaneous pressure manometry was performed
      in 10 patients with dilated cardiomyopathy before and during nitroprusside
      infusion. Ten normal subjects served as a control group. Left ventricular
      hemodynamics, regional wall motion (assessed by the area method) and regional
      wall stress (Janz method) were analyzed. RESULTS: When compared with control
      subjects, the patients with dilated cardiomyopathy had a reduced left ventricular
      ejection fraction (p < 0.01) and prolonged relaxation time constants (p < 0.01).
      Left ventricular wall motion was both hypokinetic and asynchronous in the patient
      group. In addition, systolic regional wall stress was significantly greater, the
      time to peak wall stress was longer and the regional myocardial relaxation time
      constant was greater for each ventricular area assessed in the patient group
      (each p < 0.01). Administration of nitroprusside reduced left ventricular
      pressure and increased ejection fraction in the 10 patients with dilated
      cardiomyopathy. For each region, systolic regional wall stress and the time to
      peak wall stress decreased, and both regional hypokinesia and asynchrony
      lessened. These changes in loading conditions and regional nonuniformity were
      accompanied by an improvement in both regional and global ventricular relaxation
      that was significant, particularly during the early to midrelaxation phase when
      regional asynchrony was greatest. CONCLUSIONS: These results suggest that
      myocardial relaxation is sensitive to loading conditions and regional
      nonuniformity in dilated cardiomyopathy and that load reduction can improve both
      relaxation and systolic performance of the left ventricle.

PMID- 1401608
TI  - Role of increases in heart rate in determining the occurrence and frequency of
      myocardial ischemia during daily life in patients with stable coronary artery
      disease.
AB  - OBJECTIVES: The goal of this study was to investigate the role of increases in
      heart rate in the development of ischemic episodes recorded during ambulatory
      electrocardiographic (ECG) monitoring in patients with stable coronary artery
      disease and to establish the importance of such increases in determining the
      frequency of ambulatory myocardial ischemia. BACKGROUND: The factors that
      determine the occurrence and frequency of episodes of myocardial ischemia that
      patients with stable coronary artery disease experience during daily life have
      not been clearly defined. In particular, the role of increases in heart rate in
      the development of myocardial ischemia is controversial. METHODS: To address
      these issues, 54 patients (42 men and 12 women, mean age 60.5 +/- 8 years) with
      proved coronary artery disease who had > or = 1 mm ST segment depression during
      exercise testing underwent an exercise treadmill test with use of the National
      Institutes of Health combined protocol and a 48-h period of ambulatory ECG
      monitoring. The exercise ischemic threshold was determined as the heart rate at
      the onset of ST segment depression during exercise testing. RESULTS: During
      monitoring, 48 (89%) of the 54 patients had at least one episode of ST segment
      depression (mean +/- SD 6.6 +/- 5 episodes, range 0 to 22). The majority (320 of
      359 or 89%) of ischemic episodes were preceded by an increase in heart rate > or
      = 10 beats/min; the most significant increase (22.3 +/- 10 beats/min) occurred
      during the 5-min period before the onset of the episode. An ischemic episode
      occurred 80% of the times the heart rate reached the exercise ischemic threshold.
      A strong correlation was observed between the number of times the exercise
      ischemic threshold was reached during monitoring and both the number and the
      duration of ischemic episodes (r = 0.90 and 0.71, respectively, p < 0.0001).
      CONCLUSIONS: Increases in heart rate that exceed the exercise ischemic threshold
      are commonly observed before the onset of episodes of ambulatory myocardial
      ischemia in patients with stable coronary artery disease. Moreover, such
      increases constitute an important determinant of the frequency of myocardial
      ischemia during daily life. These findings may explain the variability observed
      in the number of ischemic episodes and may have important implications for the
      mechanisms that contribute to myocardial ischemia in daily life and for the
      clinical evaluation of patients with coronary artery disease.

PMID- 1401609
TI  - Increased myocardial oxygen demand and ischemia during daily life: resurrection
      of an age-old concept.

PMID- 1401610
TI  - Long-term results of directional coronary atherectomy: predictors of restenosis.
AB  - OBJECTIVES: This study was performed to obtain better understanding of the long
      term clinical efficacy of directional coronary atherectomy. BACKGROUND: Although
      this procedure yields favorable acute results, its acceptance has been limited by
      the perception that late results (that is, freedom from restenosis) are no better
      than those of conventional angioplasty. METHODS: A total of 225 atherectomies
      performed in 190 patients between August 1988 and July 1991 were examined.
      Minimal lumen diameter of the treated segments was measured on angiograms
      obtained before, after and 6 months after intervention. RESULTS: Although most
      lesions (97%) had one or more characteristics predictive of unfavorable short- or
      long-term results after conventional angioplasty, atherectomy was successful in
      205 lesions (91%) with a mean residual stenosis of 7 +/- 16%. After subsequent
      balloon angioplasty in 16 unsuccessful atherectomy attempts, procedural success
      was 98%. There were no deaths or Q wave myocardial infarctions, and one patient
      (0.5%) underwent emergency bypass surgery. Six-month angiographic follow-up was
      obtained in 77% of the eligible patients. The overall angiographic restenosis
      rate was 32%. Predictors of a lower restenosis rate included a postprocedure
      lumen diameter > 3 mm (24% vs. 39%, p = 0.047), serum cholesterol < or = 200
      mg/dl (18% vs. 40%, p = 0.018) and recent myocardial infarction (16% vs. 37%, p =
      0.034). Life-table analysis showed a 2% mortality rate and a 26% incidence of
      other events (myocardial infarction, repeat revascularization) within the 1st
      year. The annual 5% mortality rate and 7% incidence of other events during years
      2 and 3 were related in large part to the existence or progression of disease at
      other locations. CONCLUSIONS: Six-month angiographic follow-up of patients who
      underwent directional coronary atherectomy during the 1st 3 years of our
      experience shows an overall restenosis rate of 32%, with lower rates in patients
      with a postatherectomy lumen diameter > or = 3 mm, cholesterol level < or = 200
      mg/dl or a recent myocardial infarction. Few if any events relating to the site
      of atherectomy developed after the 1st year of follow-up.

PMID- 1401611
TI  - Effect of age and coronary artery disease on response to snow shoveling.
AB  - OBJECTIVES: The objective of this study was to evaluate the effect of age and
      coronary artery disease on responses to snow shoveling. BACKGROUND: Little
      information is available on the hemodynamic and metabolic responses to snow
      shoveling. METHODS: Sixteen men with asymptomatic coronary artery disease and
      relatively good functional work capacity, 13 older normal men and 12 younger
      normal men shoveled snow at a self-paced rate. Oxygen consumption, heart rate and
      blood pressure were determined. In nine men with coronary artery disease left
      ventricular ejection fraction was evaluated with an ambulatory radionuclide
      recorder. RESULTS: Oxygen consumption during snow shoveling differed (p < 0.05)
      among groups; it was lowest (18.5 +/- 0.8 ml/kg per min) in those with coronary
      artery disease, intermediate (22.2 +/- 0.9 ml/kg/min) in older normal men and
      highest (25.6 +/- 1.3 ml/kg/min) in younger normal men. Percent peak treadmill
      oxygen consumption and heart rate with shoveling in the three groups ranged from
      60% to 68% and 75% to 78%, respectively. Left ventricular ejection fraction and
      frequency of arrhythmias during shoveling were similar to those during treadmill
      testing. CONCLUSIONS: During snow shoveling 1) the rate of energy expenditure
      selected varied in relation to each man's peak oxygen consumption; 2) older and
      younger normal men and asymptomatic men with coronary artery disease paced
      themselves at similar relative work intensities; 3) the work intensity selected
      represented hard work but was within commonly recommended criteria for aerobic
      exercise training; and 4) arrhythmias and left ventricular ejection fraction were
      similar to those associated with dynamic exercise.

PMID- 1401612
TI  - Noninvasive definition of anatomic coronary artery disease by ultrafast computed
      tomographic scanning: a quantitative pathologic comparison study.
AB  - OBJECTIVES: The aim of this study was to determine the relation between coronary
      artery calcification detected by ultrafast computed tomographic scanning and
      histopathologic coronary artery disease. BACKGROUND: Recent studies suggest that
      discrete coronary artery calcification as visualized by ultrafast computed
      tomographic scanning may facilitate the noninvasive detection or estimation, or
      both, of the in situ extent of coronary disease. Such quantitative relations have
      not been established. METHODS: Thirteen consecutive perfusion-fixed autopsy
      hearts (from eight male and five female patients aged 17 to 83 years) were
      scanned by ultrafast computed tomographic scanning in contiguous 3-mm tomographic
      sections. The major epicardial arteries were dissected free, positioned
      longitudinally and scanned again in cross section. Coronary artery calcification
      in a coronary segment was defined as the presence of one or more voxels with a
      computed tomographic density > 130 Hounsfield units. Each epicardial artery was
      sectioned longitudinally, stained and measured with a planimeter for
      quantification of cross-sectional and atherosclerotic plaque areas at 3-mm
      intervals, corresponding to the computed tomographic scans. A total of 522 paired
      coronary computed tomographic and histologic sections were studied. RESULTS:
      Direct relations were found between ultrafast computed tomographic scanning
      coronary artery calcium burden and atherosclerotic plaque area and percent lumen
      area stenosis. However, the range for plaque area or percent lumen stenosis, or
      both, associated with a given calcium burden was broad. Three hundred thirty-one
      coronary segments showed no calcification by computed tomography. Although
      atherosclerotic disease was found in several corresponding pathologic specimens,
      > 97% of these noncalcified segments were associated with nonobstructive disease
      (< 75% area stenosis); if no calcification was determined in an entire coronary
      vessel, all corresponding coronary disease was found to be nonobstructive. To
      determine the relation between arterial calcification and any atheromatous
      disease, computed tomographic calcium burden for each segment was paired with the
      histologic absence or presence of disease. Ultrafast computed tomographic
      scanning had a sensitivity and specificity of 59% and 90% and a negative and
      positive predictive value of 65% and 87%, respectively. A direct correlation was
      found (r = 0.99) between total calcium burden calculated from tomographic scans
      of the heart as a whole and scans of the arteries obtained in cross section.
      CONCLUSIONS: The detection of coronary calcification by ultrafast computed
      tomographic scanning is highly predictive of the presence of histopathologic
      coronary disease, but the use of this technique to define the extent of coronary
      disease may be limited. However, the absence of coronary calcification at any
      site is highly specific for the absence of obstructive disease.

PMID- 1401613
TI  - Decreased concentration of myofibrils and myofiber hypertrophy are structural
      determinants of impaired left ventricular function in patients with chronic heart
      diseases: a multiple logistic regression analysis.
AB  - OBJECTIVES: The aim of this study was to perform a multiple logistic regression
      analysis to identify independent structural determinants of impaired left
      ventricular function. BACKGROUND: The association between contractile failure and
      structural alterations of the myocardium has been demonstrated in several
      studies, and multiple interactions between myocardial structure and cardiac
      performance are likely. METHODS: Morphometric data assessed from 130 left
      ventricular biopsy specimens were analyzed. The endomyocardial specimens were
      obtained from 57 patients with normal coronary arteries (17 with normal left
      ventricular ejection fraction and 40 with impaired left ventricular function
      [dilated cardiomyopathy]), 15 patients with hypertrophic cardiomyopathy and 32
      patients with aortic valve disease. Transmural biopsy specimens were assessed in
      6 donor hearts before heart transplantation and in 20 patients with left anterior
      descending coronary artery disease whose specimens were obtained from the left
      ventricular anterior wall during aortocoronary bypass surgery. Global or regional
      left ventricular function was evaluated from left cineventriculograms. The volume
      fraction of cardiac fibrous tissue, intracellular volume fraction of myofibrils,
      volume fraction of myofibrils related to myocardial tissue (including fibrosis)
      and myofiber diameters were determined from semithin sections of the biopsy
      specimens with the use of light microscopic morphometry. RESULTS: Multiple
      logistic regression analysis revealed decreased volume fraction of myofibrils (p
      < 0.005) and increased fiber diameter (p < 0.002) as independent determinants of
      impaired left ventricular function. CONCLUSIONS: These data indicate that,
      independent of the underlying heart disease, both decreased concentration of
      contractile proteins and myocyte hypertrophy are independently associated with
      impaired left ventricular function.

PMID- 1401614
TI  - Relation between Doppler color flow variables and invasively determined jet
      variables in patients with aortic regurgitation.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that invasively
      derived jet variables including regurgitant orifice area and momentum determine
      the characteristics of Doppler color flow jets in patients with aortic
      regurgitation. BACKGROUND: In vitro studies have demonstrated that the velocity
      distribution of a regurgitant jet is best characterized by the momentum of the
      jet, which incorporates orifice area and velocity of flow through the orifice.
      METHODS: Peak jet momentum, peak flow rate and regurgitant orifice area were
      determined with intraaortic Doppler catheter and cardiac catheterization
      techniques in 22 patients with chronic aortic regurgitation. These invasively
      derived variables were compared with apical and parasternal long-axis Doppler
      color echocardiographic variables obtained in the catheterization laboratory.
      RESULTS: Jet momentum increased significantly with the angiographic grade of
      regurgitation. The apical color jet area of aortic regurgitation increased
      linearly with jet momentum and regurgitant orifice area in vivo, but the
      correlations were only moderately good (r = 0.63 and 0.65, respectively). Color
      jet length also increased linearly with jet momentum and with regurgitant orifice
      area. There was only a trend for Doppler color jet width to increase with all
      invasively derived jet variables. CONCLUSIONS: Whereas jet area by Doppler color
      flow imaging is directly related to both orifice area and jet momentum in vivo,
      Doppler color variables measured in planes normal to the orifice do not correlate
      well enough with either jet momentum or regurgitant orifice area to predict jet
      flow variables in patients with aortic regurgitation. It is likely that the
      important influence of adjacent boundaries will limit the use of the velocity
      distribution of aortic regurgitant jets for determining the severity of disease.

PMID- 1401615
TI  - Target lesion calcification in coronary artery disease: an intravascular
      ultrasound study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the frequency, amount and
      distribution of target lesion calcification in patients undergoing transcatheter
      therapy for symptomatic coronary artery disease. BACKGROUND: Coronary artery
      target lesion calcification may be an important determinant of response to
      transcatheter therapy: balloon angioplasty causes dissections in calcified
      lesions, directional atherectomy cuts calcium poorly, rotational atherectomy
      causes preferential ablation of calcium and laser irradiation effect may vary.
      Intravascular ultrasound imaging is a highly sensitive technique for detection of
      plaque calcification in vivo. METHODS: We performed intravascular ultrasound
      imaging before or after, or both, various transcatheter therapies in 110
      patients. These 84 men and 26 women had a mean age of 60 years and a duration of
      angina of 22 +/- 34 months. Forty-nine patients had one-vessel, 29 had two
      vessel, 25 had three-vessel and 7 had left main coronary disease. Vessels treated
      and imaged were the left main (n = 7), left anterior descending (n = 47), left
      circumflex (n = 18) and right (n = 38) coronary arteries. RESULTS: Eighty-four
      patients (76%) had target lesion calcification; 29 patients had one-quadrant, 25
      had two-quadrant, 17 had three-quadrant and 13 had four-quadrant calcification.
      The calcification was superficial in 42 patients, deep in 13 and both superficial
      and deep in 31. The axial length of calcium could be measured in 29 patients; it
      was < or = 5 mm in 11 and > or = 6 mm in 18. Fluoroscopy detected calcification
      in 50 patients (48%, p < 0.001 vs. detection by ultrasound); this proportion
      increased to 74% in patients with calcification of two or more quadrants and to
      86% in patients with calcification > or = 6 mm in length of two or more
      quadrants. Calcification was more common in patients who smoked and tended to be
      more common in patients with multivessel disease or previous coronary artery
      bypass graft surgery. CONCLUSIONS: We conclude that target lesion calcification
      occurs in 75% of patients with symptomatic coronary artery disease requiring
      angioplasty. Target lesion calcification is best detected, localized and
      quantified by intravascular ultrasound. These observations may be important in
      selecting devices for transcatheter therapy.

PMID- 1401616
TI  - Surgical treatment of adult atrial septal defect: early and long-term results.
AB  - OBJECTIVES: The purpose of this study is to determine the early and late results
      of the surgical repair of atrial septal defect in adults. BACKGROUND:
      Progressively limiting, untreated atrial septal defect can lead to the early
      death of middle-aged adults. Recently it has been suggested that the closure of
      atrial septal defects might be accomplished with interventional cardiac
      techniques. Although the long-term results of the transcatheter closure are as
      yet unknown, the outcome of surgical therapy has been shown to be beneficial for
      almost 40 years. METHODS: Between 1971 and 1991, 166 consecutive patients
      underwent surgical repair of a secundum or sinus venosus atrial septal defect, or
      both, at the Brigham and Women's Hospital, Boston. There were 120 women and 46
      men in this group; the mean age was 44 years and 58 (35%) of the patients were >
      or = 50 years old. The average pulmonary to systemic flow ratio was 3.0, and 57
      patients had a peak systolic pulmonary artery pressure > 30 mm Hg. RESULTS: There
      were two operative deaths (early mortality rate 1.2%), and 13% of the patients
      had a perioperative complication. One hundred fifty-three of the 164 survivors
      were followed up for a mean of 90 months (range 2 to 247). There were eight late
      deaths (late mortality rate 4.9%) and a late morbidity rate of 12.4% (in most
      cases due to arrhythmias). The 5- and 10-year survival rates are 98% and 94%,
      respectively, and the probability of event-free survival (with no morbidity or
      mortality) at 5 years is 97% and at 10 years is 92%. CONCLUSIONS: The results
      indicate that the surgical correction of atrial septal defect in adults is safe
      and efficacious as confirmed by 20 years of follow-up.

PMID- 1401617
TI  - Physiologic changes with maximal exercise in asymptomatic valvular aortic
      stenosis assessed by Doppler echocardiography.
AB  - OBJECTIVES: We hypothesized that the physiologic response to exercise in valvular
      aortic stenosis could be measured by Doppler echocardiography. BACKGROUND: Data
      on exercise hemodynamics in patients with aortic stenosis are limited, yet
      Doppler echocardiography provides accurate, noninvasive measures of stenosis
      severity. METHODS: In 28 asymptomatic subjects with aortic stenosis maximal
      treadmill exercise testing was performed with Doppler recordings of left
      ventricular outflow tract and aortic jet velocities immediately before and after
      exercise. Maximal and mean volume flow rate (Qmax and Qmean), stroke volume,
      cardiac output, maximal and mean aortic jet velocity (Vmax, Vmean), mean pressure
      gradient (delta P) and continuity equation aortic valve area were calculated at
      rest and after exercise. The actual change from rest to exercise in Qmax and Vmax
      was compared with the predicted relation between these variables for a given
      orifice area. Subjects were classified into two groups: Group I (rest-exercise
      Vmax/Qmax slope > 0, n = 19) and Group II (slope < or = 0, n = 9). RESULTS: Mean
      exercise duration was 6.7 +/- 4.3 min. With exercise, Vmax increased from 3.99 +/
      0.93 to 4.61 +/- 1.12 m/s (p < 0.0001) and mean delta P increased from 39 +/- 20
      to 52 +/- 26 mm Hg (p < 0.0001). Qmax rose with exercise (422 +/- 117 to 523 +/-
      209 ml/s, p < 0.0001), but the systolic ejection period decreased (0.33 +/- 0.04
      to 0.24 +/- 0.04, p < 0.0001), so that stroke volume decreased slightly (98 +/-
      29 to 89 +/- 32 ml, p = 0.01). The increase in cardiac output with exercise (6.5
      +/- 1.7 to 10.2 +/- 4.4 liters/min, p < 0.0001) was mediated by increased heart
      rate (71 +/- 17 to 147 +/- 28 beats/min, p < 0.0001). There was no significant
      change in the mean aortic valve area with exercise (1.17 +/- 0.45 to 1.28 +/-
      0.65, p = 0.06). Compared with Group I patients, patients with a rest-exercise
      slope < or = 0 (Group II) tended to be older (69 +/- 12 vs. 58 +/- 19 years, p =
      0.07) and had a trend toward a shorter exercise duration (5.3 +/- 2.9 vs. 7.3 +/-
      4.9 min, p = 0.20). There was no difference between groups for heart rate at
      rest, blood pressure, stroke volume, cardiac output, Vmax, mean delta P or aortic
      valve area. With exercise, Group II subjects had a lower cardiac output (7.4 +/-
      2.4 vs. 11.5 +/- 4.6 liters/min, p = 0.005) and a smaller percent increase in
      Vmax (3 +/- 9% vs. 22 +/- 14%, p < 0.0001). CONCLUSIONS: Doppler echocardiography
      allows assessment of physiologic changes with exercise in adults with
      asymptomatic aortic stenosis. A majority of subjects show a rest-exercise
      response that closely parallels the predicted relation between Vmax and Qmax for
      a given orifice area. The potential utility of this approach for elucidating the
      relation between hemodynamic severity and clinical symptoms deserves further
      study.

PMID- 1401618
TI  - Cardiac manifestations of cocaine abuse: a cross-sectional study of asymptomatic
      men with a history of long-term abuse of "crack" cocaine.
AB  - OBJECTIVES: The objective of this study was to evaluate the prevalence of cardiac
      abnormalities in young, asymptomatic long-term "crack" cocaine abusers.
      BACKGROUND: Although the cardiac complications of cocaine abuse have received
      widespread attention, the prevalence of cardiac abnormalities in asymptomatic
      long-term cocaine abusers is unknown. METHODS: History, physical examination,
      electrocardiogram (ECG) and echocardiogram were performed in 52 consecutive long
      term cocaine abusers admitted to a drug rehabilitation program. Findings were
      compared with those in 14 age-matched normal volunteers and 14 age-matched
      normotensive patients admitted to a psychiatric service who had a pattern of
      smoking and alcohol consumption similar to that of the study patients. RESULTS:
      The ECG findings were abnormal in 29% of cocaine abusers, and included
      nonspecific ST-T wave changes in 15%, abnormal ST segment elevation in 10%, old
      inferior infarction in 2%, old anteroseptal infarction in 2% and abnormal
      precordial R wave progression in 10%. When compared with normal volunteers and
      control patients, cocaine abusers had increased left ventricular posterior wall
      thickness (1.12 vs. 0.76 and 0.85 cm, respectively, p < 0.0001), increased septal
      thickness (1.13 vs. 0.76 and 0.86 cm, p < 0.001) and higher left ventricular mass
      index (142 vs. 84 and 94 g/m2, p < 0.0001). Left ventricular diastolic filling
      variables did not differ significantly among the three groups. Diastolic filling
      variables were similar in cocaine abusers with and without left ventricular
      hypertrophy, and the prevalence of left ventricular hypertrophy did not differ
      significantly between those who used no alcohol or < 35 ml/week of alcohol and
      those who consumed > or = 500 ml/week of alcohol. Left ventricular segmental wall
      motion abnormalities were present in 11 subjects (21%) and the ejection fraction
      was decreased (< 0.45) in 2 (4%). CONCLUSIONS: Electrocardiographic and
      echocardiographic abnormalities are common in long-term cocaine abusers. Despite
      the frequent occurrence of left ventricular hypertrophy, Doppler-derived
      diastolic filling pattern was not altered. Concomitant alcohol use did not affect
      the prevalence of these abnormalities.

PMID- 1401619
TI  - Congenital cleft of the anterior tricuspid leaflet with severe tricuspid
      regurgitation in adults.
AB  - OBJECTIVES AND BACKGROUND: Severe primary tricuspid regurgitation in the adult is
      a rare finding. This study describes the diagnostic findings and the treatment of
      an isolated congenital cleft of the anterior leaflet of the tricuspid valve as
      the morphologic substrate for severe tricuspid regurgitation. METHODS: The
      clinical, echocardiographic findings and the follow-up findings of five patients
      (all male, 20 to 56 years old) with this disorder are described. Four of the five
      patients underwent cardiac surgery that confirmed the diagnosis. RESULTS: In
      three of five patients, exertional fatigue was the limiting symptom (New York
      Heart Association functional classes II and III). The clinical findings included
      a holosystolic murmur and supraventricular arrhythmias in all patients. Cardiac
      catheterization, performed in four patients, yielded the incorrect diagnosis of
      Ebstein's anomaly in three. In one patient the cleft was associated with an
      atrial septal defect of the secundum type. In four of five patients successful
      reconstruction of the tricuspid valve with a DeVega annuloplasty was performed.
      One patient had a partial excision of the right atrium, and one had a closure of
      a coexisting atrial septal defect. One patient refused operation. CONCLUSIONS:
      Tricuspid valve anomalies can be accurately identified by Doppler
      echocardiography. Surgical repair is the treatment of choice in patients with
      severe tricuspid regurgitation due to a congenital cleft of the anterior leaflet
      of the tricuspid valve.

PMID- 1401620
TI  - Electrocardiographic detection of left ventricular hypertrophy by the simple QRS
      voltage-duration product.
AB  - OBJECTIVES: The object of this study was to assess the hypothesis that the
      product of QRS voltage and duration, as an approximation of the time-voltage
      integral of the QRS complex, can improve the electrocardiographic (ECG)
      identification of left ventricular hypertrophy. BACKGROUND: Electrocardiographic
      identification of left ventricular hypertrophy has been limited by the poor
      sensitivity of standard voltage criteria. However, increases in left ventricular
      mass can be more closely related to increases in the time-voltage integral of the
      summed left ventricular dipole than to changes in voltage or QRS duration alone.
      METHODS: Antemortem ECGs were compared with left ventricular mass at autopsy in
      220 patients. There were 95 patients with left ventricular hypertrophy, defined
      by left ventricular mass index > 118 g/m2 in men and > 104 g/m2 in women. The
      voltage-duration product was calculated as the product of QRS duration and
      Cornell voltage (Cornell product) and the 12-lead sum of QRS voltage (12-lead
      product). RESULTS: At partitions with a matched specificity of 95%, each voltage
      duration product significantly improved sensitivity for the detection of left
      ventricular hypertrophy when compared with simple voltage criteria alone (Cornell
      product 51% [48 of 95] vs. Cornell voltage 36% [34 of 95], p < 0.005 and 12-lead
      product 45% [43 of 95] vs. 12-lead voltage 31% [30 of 95], p < 0.001).
      Sensitivity of both the Cornell product and 12-lead product was significantly
      greater than that found for QRS duration alone (28%, 27 of 95, p < 0.005) and the
      Romhilt-Estes point score (27%, 26 of 95, p < 0.005), and compared favorably with
      the sensitivity of the complex Cornell multivariate score (44%, 42 of 95, p =
      NS). Comparison of receiver operating characteristic curves demonstrated that
      improved performance of the voltage-duration products for the detection of left
      ventricular hypertrophy was independent of test partition selection. In addition,
      test performance of the voltage-duration products was not significantly affected
      by the presence or absence of a bundle branch block. CONCLUSIONS: These data
      suggest that the simple product of either Cornell or 12-lead voltage and QRS
      duration can identify left ventricular hypertrophy more accurately than can
      voltage or QRS duration criteria alone and may approach or exceed the performance
      of more complex multiple regression analyses.

PMID- 1401621
TI  - Development and validation of a logistic regression-derived algorithm for
      estimating the incremental probability of coronary artery disease before and
      after exercise testing.
AB  - OBJECTIVES: Our goals were to develop and validate a multivariate algorithm for
      estimating the incremental probability of the presence of coronary artery
      disease. BACKGROUND: Multivariate methods, including logistic regression
      analysis, have been extensively applied to diagnostic exercise testing. However,
      few previous studies have included both an incremental design and external
      validation. METHODS: A retrospective collection of clinical, exercise test and
      catheterization data was performed involving four U.S. referral medical centers.
      All patients had no prior history of coronary disease and had undergone coronary
      angiography < or = 3 months after exercise stress testing. An algorithm was
      developed in one center (590 patients with a 41% prevalence of coronary artery
      disease) with the use of logistic regression analysis and was validated in the
      other three centers (1,234 patients, 70% prevalence). The algorithm incorporated
      pretest variables (age, gender, symptoms, diabetes, cholesterol), exercise
      electrocardiographic (ECG) variables (mm of ST segment depression, ST slope, peak
      heart rate, metabolic equivalents [METs], exercise angina) and one thallium
      variable. Discrimination was measured with receiver operating characteristic
      curve analysis. Calibration (that is, reliability) was assessed from a comparison
      of probability estimates and the actual prevalence of disease. RESULTS: The
      overall incremental receiver operating characteristic curve areas for the
      validation group were pretest, -0.738 +/- 0.016; postexercise ECG, 0.78 (SE
      0.017); and postthallium, 0.82 (SE 0.016); p < 0.01 for both increments. Within
      the three validation institutions, the institution with a disease prevalence
      closest to that of the derivation institution had the best incremental receiver
      operating characteristic curve areas. There was a stepwise incremental
      improvement in calibration especially from exercise ECG to thallium testing.
      CONCLUSIONS: An incremental multivariate algorithm derived in one center reliably
      estimated disease probability in patients from three other centers. The
      incremental value of testing was best demonstrated when the derivation and
      validation groups had a similar disease prevalence. This algorithm may be useful
      in decision making that relates to the diagnosis of coronary disease.

PMID- 1401622
TI  - Adjunctive thrombolytic therapy for angioplasty in ischemic rest angina: results
      of a double-blind randomized pilot study.
AB  - OBJECTIVES: A multicenter pilot study was instituted to assess the role of
      intracoronary thrombolytic therapy during angioplasty for ischemic rest angina.
      BACKGROUND: Acute thrombotic coronary occlusion is increased during angioplasty
      for unstable angina, and intracoronary thrombolytic agents have been used to
      maintain patency. Prophylactic use of intracoronary thrombolytic agents has been
      advocated in certain high risk subgroups, although no studies have randomized
      therapy. METHODS: Ninety-three patients with either unstable angina and pain at
      rest (trial A, 66 patients) or postinfarction pain at rest (trial B, 27 patients)
      were randomized in double-blind fashion to administration of either intracoronary
      urokinase, 150,000 U, or saline solution placebo given immediately before
      angioplasty. Cineangiograms of the culprit lesion were recorded and analyzed in
      blinded fashion by a core laboratory for definite or possible (haziness) filling
      defects 15 min after angioplasty or after acute closure. RESULTS: Urokinase
      decreased filling defects at 15 min after angioplasty in comparison with placebo
      (14% vs. 29%, respectively, p = 0.08). Four patients in each treatment group
      developed acute vessel closure. However, although urokinase significantly reduced
      the incidence of filling defects in trial A (3% vs. 23%, p = 0.03), the drug had
      no effect at the selected dose in trial B (42% vs. 43%, respectively). Acute
      vessel closure occurred significantly more frequently in trial B than in trial A,
      and urokinase at the selected dose also had no effect. Ischemic events after
      angioplasty appeared to be related more to dissection than to thrombosis,
      although redilation, which was more frequent after placebo administration, may
      have reduced their incidence as well as that of acute closure. CONCLUSIONS: These
      data suggest a possible role for intracoronary urokinase during angioplasty for
      unstable angina. The lack of effect after infarction may represent a greater
      thrombus burden or degree of plaque disruption. A trial utilizing higher doses of
      urokinase in a larger patient group is in progress.

PMID- 1401624
TI  - Effects of sotalol on the signal-averaged electrocardiogram in patients with
      sustained ventricular tachycardia: relation to suppression of inducibility and
      changes in tachycardia cycle length.
AB  - OBJECTIVES: This study examines the effects of sotalol on the signal-averaged
      electrocardiogram (ECG) in patients with spontaneous and inducible sustained
      ventricular tachycardia and correlates these findings with the effect of sotalol
      on tachycardia inducibility and tachycardia rate. BACKGROUND: Standard
      electrocardiography generally does not detect any change in the duration of the
      QRS complex resulting from sotalol therapy. However, the signal-averaged ECG is
      more sensitive than the standard ECG for detecting changes in QRS duration
      induced by antiarrhythmic drugs and can also detect changes in late potential
      duration. METHODS: Signal-averaged electrocardiography was performed before
      therapy in 30 patients with spontaneous and inducible ventricular tachycardia,
      and both electrophysiologic study and a signal-averaged ECG were repeated during
      therapy with d,l-sotalol. RESULTS: During sotalol therapy the signal-averaged QRS
      duration decreased by 2.6 +/- 6.6 ms in the 11 patients with no inducible
      tachycardia during therapy, whereas it increased by 3.8 +/- 5.8 ms (p = 0.01) in
      the 19 patients with inducible tachycardia during therapy. In the latter group
      there was a significant positive correlation between prolongation of tachycardia
      cycle length and prolongation of late potential duration by sotalol (r = 0.56, p
      = 0.01). CONCLUSIONS: Sotalol can alter QRS and late potential duration as
      measured by the signal-averaged ECG. Prolongation of QRS duration or late
      potential duration may reflect a slowing of conduction by sotalol that may
      interfere with this agent's antiarrhythmic efficacy and slow ventricular
      tachycardia.

PMID- 1401623
TI  - Effects of steal-prone anatomy on intraoperative myocardial ischemia. The SPI
      Research Group.
AB  - OBJECTIVES: Our study objective was to determine whether the presence of steal
      prone anatomy conferred an increased risk in the development of intraoperative
      myocardial ischemia. BACKGROUND: Coronary artery steal of collateral blood flow
      has been demonstrated for many vasodilators, including isoflurane, the most
      commonly used inhalational anesthetic agent in the United States. It has been
      postulated that patients with steal-prone anatomy (total occlusion of one
      coronary artery that is supplied distally by collateral flow from another
      coronary artery with a > or = 50% stenosis) may be particularly at risk for the
      development of intraoperative myocardial ischemia when an anesthetic with a
      vasodilator property is being administered. METHODS: We evaluated the risk of
      myocardial ischemia under isoflurane anesthesia (vs. a high dose narcotic
      technique using sufentanil) using continuous intraoperative electrocardiography
      and transesophageal echocardiography in patients with and without steal-prone
      anatomy undergoing coronary artery bypass graft surgery. RESULTS: Sixty-two (33%)
      of the 186 patients had steal-prone anatomy: in 5 (8%) the collateral-supplying
      vessel was > or = 50% to 69% stenosed, in 24 (39%) it was > or = 70% to 89%
      stenosed and in 33 (53%) it was > or = 90% stenosed. The incidence of ischemia
      (transesophageal echocardiography or intraoperative electrocardiography, or both)
      was similar in patients with and without steal-prone coronary anatomy (18 [29%]
      of 62 patients vs. 39 [31%] of 124 patients, p = 0.87, 95% confidence interval = 
      0.13 to 0.17). The incidence of intraoperative ischemia was similar in patients
      who received isoflurane or sufentanil anesthesia (20 [32%] of 62 patients vs. 37
      [30%] of 124 patients, p = 0.87). The incidence of tachycardia and hypotension
      was low (increases in heart rate = 9.8%, and decreases in systolic blood pressure
      = 10.8% of total monitoring time during the prebypass period compared with
      preoperative baseline values). The incidence of adverse cardiac outcome was
      similar in patients with and without preoperative steal-prone coronary anatomy (4
      [7%] of 62 patients vs. 14 [11%] of 124 patients, p = 0.53). CONCLUSIONS: These
      findings demonstrate that under strict hemodynamic control the presence of steal
      prone anatomy does not confer an increased risk in the development of
      intraoperative myocardial ischemia.

PMID- 1401625
TI  - Electrocardiographic and electrophysiologic characteristics of anterior,
      midseptal and right anterior free wall accessory pathways.
AB  - OBJECTIVES: The objective of this study was to define the electrocardiographic
      (ECG) and electrophysiologic characteristics of midseptal, anteroseptal and right
      anterior free wall accessory pathways. METHODS: The fully pre-excited 12-lead
      surface ECGs and ECGs during orthodromic atrioventricular (AV) reentrant
      tachycardia were compared for 13 patients with an anteroseptal, 7 with a
      midseptal and 7 with a right free wall accessory pathway. Routine
      electrophysiologic studies were performed in all and stimulation of the right
      ventricular summit during tachycardia was accomplished in 10 patients. RESULTS:
      Differences in the surface ECGs were not sufficiently sensitive to distinguish
      among accessory pathway locations. Premature ventricular complexes induced from
      the right ventricular septal summit during ventricular activation either advanced
      the succeeding atrial depolarization or terminated the tachycardia in three of
      six patients with a septal pathway and in none of the four with a right anterior
      pathway. The change in ventriculoatrial (VA) interval with the development of
      right bundle branch block during orthodromic AV tachycardia proved most helpful
      in distinguishing these pathways. Patients with a right anterior free wall
      pathway showed a change in VA interval > or = 40 ms, whereas those with an
      anteroseptal pathway showed changes of 20 to 30 ms and those with a midseptal
      pathway showed no change. CONCLUSIONS: Anteroseptal, midseptal and right anterior
      free wall pathways may be distinguished by using programmed stimulation of the
      summit of the right ventricular septum and especially with changes in the VA
      interval with development of right bundle branch block during orthodromic AV
      reentrant tachycardia.

PMID- 1401626
TI  - Frequency analysis of signal-averaged electrocardiogram in patients with right
      ventricular tachycardia.
AB  - OBJECTIVES: The purpose of this study was to analyze the frequency content of
      signal-averaged electrocardiograms (ECGs) in patients with idiopathic ventricular
      tachycardia of right ventricular origin and in patients with arrhythmogenic right
      ventricular dysplasia. BACKGROUND: The late potentials in the time domains are
      usually found in patients with arrhythmogenic right ventricular dysplasia. They
      are not usually found in patients with idiopathic ventricular tachycardia of
      right ventricular origin. METHODS: Fast Fourier transform analysis of signal
      averaged ECGs was performed with the use of a Blackman-Harris window in 43
      subjects: 20 normal volunteers (group I), 12 patients with idiopathic ventricular
      tachycardia of right ventricular origin (group II) and 11 patients with
      arrhythmogenic right ventricular dysplasia (group III), and the frequency
      spectrum was displayed in a three-dimensional graph. Area ratio (ratio of the
      area under the spectral plot from 40 to 120 Hz to the area from 0 to 120 Hz) was
      calculated in all subjects. RESULTS: Area ratio was significantly higher in group
      II than in group I (243 +/- 45 vs. 196 +/- 15, p < 0.01) and significantly higher
      in group III (396 +/- 51) than in group I or II (p < 0.001). The high frequency
      components in group II were confined within the QRS complex in the three
      dimensional graph, whereas those in group III extended outside the QRS complex.
      CONCLUSIONS: Frequency analysis of the signal-averaged ECG with fast Fourier
      transform analysis can detect the high frequency components in patients with
      right ventricular tachycardia, including idiopathic ventricular tachycardia and
      arrhythmogenic right ventricular dysplasia.

PMID- 1401627
TI  - Improved reproducibility of left atrial and left ventricular measurements by
      guided three-dimensional echocardiography.
AB  - OBJECTIVES: The objective of this study was to determine whether guided three
      dimensional echocardiography could improve the reproducibility of left atrial and
      left ventricular anteroposterior measurements over that of standard unguided two
      dimensional echocardiography. BACKGROUND: Although these measurements are
      standard indexes for evaluating chamber size, their use is limited by significant
      interobserver variability largely due to variable image plane positioning. To
      improve measurement accuracy and reproducibility, we have developed a three
      dimensional echocardiograph that displays the line of intersection of the real
      time image with a previously saved orthogonal reference image. This display shows
      the relation of the real-time image to anatomic landmarks in its third,
      nonvisualized dimension and may be used to guide image positioning. METHODS:
      Three pairs of operators independently performed unguided two-dimensional and
      guided three-dimensional examinations on three groups of 10 patients each. The
      left atrium was measured in a plane through the inferior surface of the aortic
      cusps and the left ventricle in a plane perpendicular to its long axis 1 cm below
      the mitral leaflet tips. Interobserver variability of these measurements on
      unguided parasternal long-axis images and on guided short-axis images was
      assessed. RESULTS: The standard unguided two-dimensional examination was
      associated with an interobserver variability of 14.6% and 9.1% for atrial and
      ventricular measurements, respectively. Guided three-dimensional echocardiography
      significantly reduced interobserver variability to 5.0% and 3.1%, respectively,
      for the same measurements (p < 0.005 by McNemar's test). CONCLUSIONS: Significant
      interobserver variability occurs with standard unguided two-dimensional
      echocardiographic measurement of left atrial and left ventricular dimensions.
      Guided three-dimensional echocardiography achieves a nearly threefold improvement
      of reproducibility of these measurements and provides the basis for improved
      serial evaluation and comparison of atrial and ventricular size by different
      operators.

PMID- 1401628
TI  - Quantification of left to right atrial shunts with velocity-encoded cine nuclear
      magnetic resonance imaging.
AB  - OBJECTIVES: The purpose of this study was to evaluate the ability of velocity
      encoded nuclear magnetic resonance (NMR) imaging to quantify left to right
      intracardiac shunts in patients with an atrial septal defect. BACKGROUND:
      Quantification of intracardiac shunts is clinically important in planning
      therapy. METHODS: Velocity-encoded NMR imaging was used to quantify stroke flow
      in the aorta and in the main pulmonary artery in a group of patients who were
      known to have an increased pulmonary to systemic flow ratio (Qp/Qs). The velocity
      encoded NMR flow data were used to calculate Qp/Qs, and these values were
      compared with measurements of Qp/Qs obtained with oximetric data derived from
      cardiac catheterization and from stroke volume measurements of the two ventricles
      by using volumetric data from biphasic spin echo and cine NMR images obtained at
      end-diastole and end-systole. RESULTS: Two independent observers measured Qp/Qs
      by using velocity-encoded NMR imaging in 11 patients and found Qp/Qs ranging from
      1.4:1 to 3.9:1. These measurements correlated well with both oximetric data (r =
      0.91, SEE = 0.35) and ventricular volumetric data (r = 0.94, SEE = 0.30).
      Interobserver reproducibility for Qp/Qs by velocity-encoded NMR imaging was good
      (r = 0.97, SEE = 0.20). CONCLUSIONS: Velocity-encoded NMR imaging is an accurate
      and reproducible method for measuring Qp/Qs in left to right shunts. Because it
      is completely noninvasive, it can be used to monitor shunt volume over time.

PMID- 1401629
TI  - Left ventricular mass and body size in normotensive children and adults:
      assessment of allometric relations and impact of overweight.
AB  - OBJECTIVES: This study was designed to determine the most appropriate method to
      normalize left ventricular mass for body size. BACKGROUND: Left ventricular mass
      has been normalized for body weight, surface area or height in experimental and
      clinical studies, but it is uncertain which of these approaches is most
      appropriate. METHODS: Three normotensive population samples--in New York City
      (127 adults), Naples, Italy (114 adults) and Cincinnati, Ohio (444 infants to
      young adults)--were studied by echocardiography. Relations of left ventricular
      mass to body size were similar in all normal weight groups, as assessed by linear
      and nonlinear regression analysis, and results were pooled (n = 611). RESULTS:
      Left ventricular mass was related to body weight to the first power (r = 0.88),
      to body surface area to the 1.5 power (r = 0.88) and to height to the 2.7 power
      (r = 0.84), consistent with expected allometric (growth) relations between
      variables with linear (height), second-power (body surface area) and volumetric
      (left ventricular mass and body weight) dimensions. Strong residual relations of
      left ventricular mass/body surface area to body surface area (r = 0.54) and of
      ventricular mass/height to height (r = 0.72) were markedly reduced by
      normalization of ventricular mass for height2.7 and body surface area1.5. The
      variability among subjects of ventricular mass was also reduced (p < 0.01 to p <
      0.002) by normalization for body weight, body surface area, body surface area1.5
      or height2.7 but not for height. In 20% of adults who were overweight,
      ventricular mass was 14% higher (p < 0.001) than ideal mass predicted from
      observed height and ideal weight; this increase was identified as 14% by left
      ventricular mass/height2.7 and 9% by ventricular mass/height, whereas indexation
      for body surface area, body surface area1.5 and body weight erroneously
      identified left ventricular mass as reduced in overweight adults. CONCLUSIONS:
      Normalizations of left ventricular mass for height or body surface area introduce
      artifactual relations of indexed ventricular mass to body size and errors in
      estimating the impact of overweight. These problems are avoided and variability
      among normal subjects is reduced by using left ventricular mass/height2.7. Simple
      nomograms of the normal relation between height and left ventricular mass allow
      detection of ventricular hypertrophy in children and adults.

PMID- 1401630
TI  - Tachycardia, contractility and volume loading alter conventional indexes of
      coronary flow reserve, but not the instantaneous hyperemic flow versus pressure
      slope index.
AB  - OBJECTIVES AND BACKGROUND: Because measurements of flow reserve are often made in
      the setting of fluctuating hemodynamic variables that cause alterations in basal
      or hyperemic coronary blood flow, traditional flow reserve indexes may be
      difficult to interpret. Prior work in this laboratory has suggested that the
      instantaneous hyperemic flow versus pressure slope index is a more
      hemodynamically stable alternative to measures of flow reserve. Although this
      index has no hemodynamic dependence on changes in aortic pressure, the extent to
      which it is affected by other factors that alter myocardial work is unknown.
      Therefore, the purpose of this investigation was to analyze the effects of
      tachycardia (induced by atrial pacing at 10 beats/min above the basal heart
      rate), dobutamine infusion (10 micrograms/kg per min) and saline solution volume
      loading (500 ml) on measurements of traditional coronary flow reserve, the
      resistance reserve ratio and the instantaneous hyperemic flow versus pressure
      slope index. METHODS: Twenty-nine open chest anesthetized dogs were studied in
      four sequential stages: baseline, tachycardia, dobutamine infusion and saline
      solution volume loading. Traditional coronary flow reserve was defined as the
      ratio of hyperemic coronary blood flow to basal coronary blood flow, the
      resistance reserve ratio as the ratio of basal coronary resistance to hyperemic
      coronary resistance and the instantaneous hyperemic flow versus pressure slope
      index as the slope of the instantaneous relation between diastolic hyperemic
      coronary blood flow and diastolic aortic pressure normalized by perfusion bed
      weight. Hyperemia was induced by intravenous adenosine infusion (1 mg/kg per
      min). Mean aortic pressure was kept nearly constant during the interventions by
      manipulation of an aortic clamp or a vena caval snare. RESULTS: The final study
      group comprised 18 open chest dogs. Coronary flow reserve was significantly
      decreased by tachycardia (3.7 +/- 1.2 to 3.0 +/- 1.2, p < 0.0001), decreased by
      saline solution volume loading (3.2 +/- 1.3 vs. 2.7 +/- 0.8, p = 0.06) and
      significantly increased by dobutamine infusion (3.2 +/- 1.3 to 4.3 +/- 1.5, p <
      0.0005). In contrast, the instantaneous hyperemic flow versus pressure slope
      index was not affected by the three interventions (7.4 +/- 3.1 vs. 7.3 +/- 3.3,
      7.4 +/- 3.2 vs. 7.4 +/- 3.4 and 7.5 +/- 3.1 vs. 7.3 +/- 3.4, respectively, all p
      = NS). The changes observed in the resistance reserve ratio were of similar or
      greater magnitude and significance to the changes in coronary flow reserve.
      CONCLUSIONS: The instantaneous hyperemic flow versus pressure slope index offers
      a hemodynamically stable alternative to measures of vascular reserve because it
      is independent of moderate changes in heart rate, contractility and volume
      loading that may occur commonly in clinical situations.

PMID- 1401631
TI  - Prediction of immediate ventricular arrhythmias after coronary artery ligation.
AB  - OBJECTIVES: Our aim was to test the hypothesis that increased beat to beat
      morphologic variations in the body surface electrocardiogram (ECG) are associated
      with fragmented diastolic electrical activity that appears after coronary artery
      ligation and to correlate the appearance of spontaneous ventricular fibrillation
      after coronary ligation with the magnitude of the ECG beat to beat variability.
      BACKGROUND: Unstable and variably delayed electrical activation precedes the
      development of ventricular fibrillation in dogs with acute ischemia. Detection of
      these highly variable low amplitude signals from the body surface is currently
      impossible. We have developed a system designed to measure the degree of beat to
      beat variability of the ECG. METHODS: With high fidelity electrocardiography,
      subtle beat to beat ECG morphologic variations were detected in epicardial and
      body surface electrograms and quantified as the variance of the ECG voltage at
      specific points of the cardiac cycle. The ratio of the variance at the QRS offset
      to that of the QRS onset (beat to beat variability index) was then calculated.
      RESULTS: Ventricular fibrillation developed in 12 of 27 dogs after left anterior
      descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately
      (< 15 min) after ligation; in the other 5 it developed late (> 15 min) after
      ligation. Dogs with subsequently immediate ventricular fibrillation had a
      significantly higher beat to beat variability index than that of dogs with late
      or no ventricular fibrillation both before coronary ligation (4.7 +/- 1.4 vs. 1.1
      +/- 0.2 and 0.8 +/- 0.1, respectively, p < 0.001) and after ligation (6.4 +/-
      2.6, 1.0 +/- 0.6 and 1.2 +/- 0.6, respectively, p < 0.001). In dogs that
      developed ventricular fibrillation immediately after coronary ligation, the
      arrhythmia was preceded by fragmented diastolic electrical activity on the
      epicardial electrogram and a simultaneous increase in the beat to beat
      morphologic variability of the terminal portion of the body surface ECG QRS
      complex. CONCLUSIONS: Beat to beat QRS offset morphologic variations appear to be
      increased before and further increased after coronary artery ligation in dogs
      that develop ventricular fibrillation immediately after ligation. Increased beat
      to beat variability index may be associated with the presence of
      electrophysiologic instability and can predict early ventricular fibrillation.

PMID- 1401632
TI  - Comparison of technetium-99m sestamibi and thallium-201 retention characteristics
      in canine myocardium.
AB  - OBJECTIVES: The aim of this study was to compare the myocardial retention of
      technetium-99m (Tc-99m) sestamibi and thallium-201 over a wide range of blood
      flow at different time points after tracer injection. BACKGROUND: Technetium-99m
      sestamibi has been proposed as a new perfusion tracer with better physical
      characteristics than those of thallium-201 for scintigraphic imaging. However, no
      studies have simultaneously compared the ability of both tracers to assess
      myocardial blood flow during pharmacologic vasodilation. METHODS: The myocardial
      retention of Tc-99m sestamibi and thallium-201 were compared over a wide range of
      blood flow induced by regional coronary occlusion and dipyridamole infusion in an
      open chest dog model. Myocardial retention of both tracers was determined by in
      vitro tissue counting at 2, 5, and 20 min after tracer injection and was
      correlated with microsphere-determined blood flow. RESULTS: Thallium-201
      demonstrated greater absolute tissue retention than did Tc-99m sestamibi. At 2
      min after tracer injection, there was an almost linear relation between the
      retention of both tracers and myocardial blood flow over a wide flow range.
      However, this relation was not maintained over time. At 20 min after injection,
      the retention of both tracers underestimated myocardial blood flow at higher flow
      rates. At 2, 5 and 20 min after injection, increments of relative tracer
      retention between the different levels of flow were always greater for thallium
      201 than for Tc-99m sestamibi. CONCLUSIONS: Thallium-201 displays more suitable
      physiologic characteristics as a flow tracer and may allow better differentiation
      of myocardial regions with different levels of coronary flow reserve. For both
      tracers, early cardiac imaging may minimize underestimation of blood flow at
      higher flow rates.

PMID- 1401633
TI  - The restenosis paradigm revisited: an alternative proposal for cellular
      mechanisms.
AB  - Coronary restenosis is a reparative response to arterial injury during
      angioplasty, and remains a major clinical problem. The reasons for treatment
      failures likely stem from our incomplete understanding of the cellular mechanisms
      in restenotic neointimal formation. Restenosis is thought to result from
      migration and replication of medial smooth muscle cells to form an obstructive
      neointima, a concept neither observed nor demonstrated in humans. An alternative
      hypothesis for restenosis is based on observations in the porcine coronary injury
      model. In this model, there are three cellular stages in neointimal formation:
      thrombotic (stage I), cellular recruitment (stage II) and proliferative (stage
      III). The thrombotic stage occurs early and consists of platelets, fibrin and red
      blood cells accumulating at the vessel injury site. In the recruitment stage, the
      mural thrombus itself develops an endothelium, followed by a mononuclear
      leukocytic infiltrate beginning on the lumen side of the vessel. In the
      proliferative stage, a "cap" of actin-positive cells forms on the lumen surface
      and progressively thickens. These cells do not arise from media at the injury
      site. Extracellular matrix secretion and additional recruitment likely add to
      neointimal volume during this phase. Thrombus assumes a major role in restonosis
      by providing an absorbable matrix into which smooth muscle cells proliferate.
      Further studies are needed to validate or modify this hypothesis.

PMID- 1401634
TI  - Recertification in cardiovascular disease. Cardiovascular Disease Board of the
      American Board of Internal Medicine.

PMID- 1401635
TI  - Striving for effective communication.

PMID- 1401636
TI  - Newly elected members of the College in August 1992. American College of
      Cardiology.

PMID- 1401637
TI  - Unethical placebo assignment in clinical trials of thrombolysis.

PMID- 1401638
TI  - Diastolic function in hypertrophic cardiomyopathy.

PMID- 1401639
TI  - Respiratory effects of air pollution on allergic disease.
AB  - Allergic patients have an increased susceptibility to the adverse effects of both
      natural and man-made air pollutants. This goes for both indoor and outdoor air
      pollutants and manifests itself with biochemical, cellular, and pathophysiologic
      expressions of adverse health effects in allergic individuals. Also
      occupationally induced allergic diseases will remain very important. This area
      has been reviewed recently by Cullen et al. Since allergic patients comprise
      somewhere between 15% and 20% of the population, this increased susceptibility is
      of crucial importance not only for medical care and research but for legislative
      and regulatory consideration to protect these vulnerable individuals.

PMID- 1401640
TI  - Systemic reactions from allergen immunotherapy.

PMID- 1401641
TI  - The association of individual allergen reactivity with respiratory disease in a
      national sample: data from the second National Health and Nutrition Examination
      Survey, 1976-80 (NHANES II).
AB  - The independent association of individual allergen reactivity with respiratory
      disease was evaluated with use of the second National Health and Nutrition
      Examination Survey, a sample of the U.S. white civilian population, ages 6 to 24
      years (n = 4295). Eight, 1:20 wt/vol, 50% glycerol, unstandardized extracts were
      administered by prick puncture. Allergen reactivity was reported as the percent
      with a mean erythema diameter 10.5 mm or greater at 20 minutes. Only the
      prevalence of asthma and allergic rhinitis increased with the increasing number
      of positive allergen skin tests. The independent association of individual
      allergen reactivity with respiratory disease was quantified with logistic models
      that included other allergen reactivity, age, sex, smoking, and region. Asthma
      was associated with reactivity to house dust (odds ratio, 2.9; 95% confidence
      interval [CI] 1.7 to 5) and Alternaria (odds ratio, 5.1; 95% CI: 2.9 to 8.9).
      Allergic rhinitis was associated with reactivity to ragweed (odds ratio, 2.3; 95%
      CI: 1.5 to 3.3); ryegrass (odds ratio, 2.8; 95% CI: 1.8 to 4.3); house dust (odds
      ratio, 2.5; 95% CI: 1.6 to 3.9); Alternaria (odds ratio, 2.3; 95% CI: 1.5 to
      3.4). Asthma only (without allergic rhinitis) was associated with dust and
      Alternaria. Allergic rhinitis only (without asthma) was associated with ryegrass,
      ragweed, and house dust. When both asthma and allergic rhinitis were present,
      only house dust and Alternaria remained associated. These findings highlight the
      association of specific allergens with upper and lower respiratory diseases and
      the interactions among coexisting respiratory diseases.

PMID- 1401642
TI  - Specific serum immunopatterns in clinical phases of allergic bronchopulmonary
      aspergillosis.
AB  - Immunoblotting, radioallergosorbent test (RAST), and enzyme-linked immunosorbent
      assay (ELISA) were performed to determine specific IgE and IgG responses to
      Aspergillus fumigatus (Af) allergens (IgE-Af; IgG-Af). Serology results were
      compared in patients with allergic bronchopulmonary aspergillosis (ABPA) (n =
      43), patients with Aspergillus fumigatus-associated asthma (Af-asthma) (n = 26),
      and healthy individuals (n = 3). In patients with different clinical phases of
      ABPA, three specific immunopatterns were found by immunoblotting. It is proposed
      to classify ABPA into the active, intermediate, and remission phase with respect
      to the specific immunoresponse to Af-allergens and asthma symptoms. First, the
      active phase of ABPA is characterized by a fully developed specific
      immunoresponse to Af-allergens and severe asthma. Second, the intermediate phase
      includes patients with elevated specific immunologic findings without asthma
      symptoms. Third, the remission phase is characterized by a weak specific
      immunoresponse to Af-allergens after a long-term asymptomatic period. No
      correlation occurred between specific immunopatterns and irreversible
      brochopulmonary lesions. The IgE-Af RAST and IgG-Af ELISA titers of patients with
      ABPA in the active and intermediate phase were significantly higher compared with
      patients with ABPA in remission phase and with patients with Af-asthma. In
      particular, the demonstration of positive IgG-Af ELISA titer generally allows the
      serologic discrimination of patients with asthma and ABPA from patients with Af
      asthma in clinical practice. The present study revealed that immunoblots of most
      patients with Af-asthma were negative. Immunoblotting demonstrated an IgG
      reactivity exclusively to low molecular weight (MW) Af-allergens in 8 out of 26
      patients with Af-asthma and in the three healthy individuals, and this IgG
      response may reflect naturally occurring antibodies.

PMID- 1401643
TI  - The role of water temperature and laundry procedures in reducing house dust mite
      populations and allergen content of bedding.
AB  - The effects of various laundry procedures on house dust mites and their allergens
      have been established. All mites were killed by water temperatures 55 degrees C
      or greater. Killing at lower temperatures was not enhanced by any of the pure
      detergents or laundry products tested. A cold cycle of laundry washing with or
      without laundry powder did not remove most live mites from bedding, however, the
      allergen concentration (Der p I/gm fine dust) was reduced by more than 90%. Dry
      cleaning did not reduce the allergen concentration of the dust, although most, if
      not all, mites were killed.

PMID- 1401644
TI  - Fish hypersensitivity. II: Clinical relevance of altered fish allergenicity
      caused by various preparation methods.
AB  - In double-blind, placebo-controlled, oral food challenges with fish, a 12-fold
      higher false-negative rate was found compared with other food antigens. In an
      effort to elucidate this discrepancy, cooked lyophilized fish extracts (used in
      double-blind, placebo-controlled, oral food challenges) were compared with
      cooked, nonlyophilized fish extracts (used in open challenges) by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, immunoblot, and ELISA-inhibition
      assays. Altered fish allergenicity as a result of food processing was examined
      with canned tuna and salmon. Forty-five children and young adults with food
      allergies, including 18 patients with IgE-mediated hypersensitivity to fish, were
      challenged with canned tuna. All 45 challenges with canned tuna were negative.
      Two of these patients are allergic to salmon and also have negative reactions to
      challenges with canned salmon. In vitro investigation by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of tuna and salmon extracts revealed a
      striking loss of definable protein fractions in the canned fish extract when
      compared with raw and cooked fish extracts, and immunoblot analyses demonstrated
      minimal IgE-specific binding to the canned fish extracts. In addition, decreased
      allergenicity of the canned tuna and salmon was demonstrated by ELISA-inhibition
      assay and by negative oral challenges with canned salmon in two patients allergic
      to salmon. Collectively, these findings suggest that some of the major allergens
      responsible for IgE-mediated food allergy to fish are more labile than previously
      recognized.

PMID- 1401645
TI  - Safety and efficacy of fire ant venom in the diagnosis of fire ant allergy.
AB  - Thirty-three adult patients who had had systemic allergic reactions to fire ant
      stings and 33 insect-nonallergic control subjects were skin tested with single
      lots of Solenopsis invicta (Sol i) fire ant venom (IFAV) and two commercially
      available imported fire ant whole body extracts (IFA WBEs). All three extracts
      were analyzed for protein concentration. Sol i II and Sol i III concentrations
      were each assayed by means of two ELISAs with complementary monoclonal
      antibodies, one species specific and one cross-reactive. Radioallergosorbent test
      (RAST) to IFAV and both IFA WBEs was performed on sera from all study subjects.
      Both IFA WBEs contained high concentrations of fire ant body proteins. Sol i II
      and III concentrations each varied twofold between the two IFA WBE preparations.
      Patients were generally more reactive to IFAV than IFA WBE by skin testing and
      RAST. IFAV RAST appeared to be a more sensitive assay than IFA WBE RAST. No
      adverse reactions occurred to skin testing with IFAV, but intradermal testing
      with higher concentrations of IFA WBE caused delayed large local reactions in 16
      of 30 (53%) control subjects. These reactions were attributed to the large
      amounts of extraneous body proteins in IFA WBE. These results (1) demonstrate
      that skin testing with IFAV is safe, (2) indicate that IFAV is more potent than
      IFA WBE, and (3) suggest that IFAV may be the superior reagent for diagnosis of
      fire ant allergy.

PMID- 1401647
TI  - Anaphylaxis to carboplatin--a new platinum chemotherapeutic agent.

PMID- 1401646
TI  - Olfactory loss and allergic rhinitis.
AB  - Olfactory loss is of importance for allergists to investigate in their patients,
      because if it is due to either allergic rhinitis or nonallergic rhinitis, it is
      potentially reversible. One should be sure to consider nasal polyposis and
      inflammation from chronic sinusitis, especially of the ethmoidal sinuses. Simple
      screening in the office can be achieved with an odor identification test of
      widely available substances as described above. Should there be no response to
      treatment or if the patient has a history of chronic sinusitis, recalcitrant
      nasal polyposis, or previous otolaryngologic procedures, further evaluation
      including rhinoscopy may be required. Recent olfactory loss in the absence of
      nasal symptoms and in the absence of abnormalities in the nasal cavity should
      suggest further investigation to look for a more central process. Morphologic
      investigation with electron microscopy of the olfactory epithelium and the
      superior nasal cavity is just beginning. The impact of inflammation in this area
      awaits investigation.

PMID- 1401648
TI  - The incidence of severe adverse reactions to food in Colorado.

PMID- 1401649
TI  - High-dose systemic glucocorticoid therapy in the treatment of severe asthma: a
      case of resistance and patterns of response.

PMID- 1401650
TI  - Detection of decreased cytotoxic effector CD8+ T lymphocytes in atopic dermatitis
      by flow cytometry.

PMID- 1401651
TI  - IgG2 and IgG4 subclass deficiency and Evan's syndrome in an adult patient.

PMID- 1401652
TI  - Mediators of allergic rhinitis.
AB  - Although histamine is the principal mediator of the immediate allergic reaction,
      other inflammatory mediators as well as neuropeptides also contribute to
      rhinorrhea and nasal congestion. Within minutes of exposure to allergen, mast
      cells produce histamine, leukotriene C4, and prostaglandin D2. A concomitant
      increase occurs in neuropeptides and bradykinin. In vitro mast cell activation
      also leads to the release of tumor necrosis factor--alpha, several interleukins,
      and granulocyte-macrophage colony--stimulating factor. Because all these various
      mediators and neuropeptides may play a role in producing rhinorrhea and
      congestion, antihistamines alone cannot control all of the symptoms of allergic
      rhinitis. However, the combination of antihistamines with topical corticosteroids
      can inhibit the generation, release, and activity of most if not all of the
      mediators potentially involved in the allergic response.

PMID- 1401653
TI  - Inhibition of mediator release during the early reaction to antigen.
AB  - A nasal lavage model and a new filter paper disk model have been used to measure
      biologic and physiologic responses to antigen challenge in patients with allergic
      rhinitis. Pretreatment of subjects with cetirizine reduced the number of sneezes
      induced by antigen challenge but did not significantly reduce levels of histamine
      or prostaglandin D2 in a double-blind, placebo-controlled trial with the lavage
      model. Pretreatment with 60 or 300 mg of terfenadine did significantly reduce
      levels of histamine, kinin, albumin, and TAME-esterase activity in a double
      blind, placebo-controlled study with this model. Again with the nasal lavage
      model, a double-blind, placebo-controlled comparison of pretreatment with 60 mg
      of terfenadine or 10 mg of loratadine showed that both agents significantly
      reduced sneezing. Both drugs also lowered levels of antigen-induced histamine and
      TAME-esterase, but only terfenadine did so significantly. In a double-blind,
      placebo-controlled study, the new disk method showed that terfenadine reduced
      sneezing but not nasal congestion in eight patients with allergic rhinitis.
      Terfenadine significantly reduced the weight of nasal secretions on both sides of
      the nose and significantly reduced histamine on the ipsilateral side.

PMID- 1401654
TI  - Dietetics education: are we missing the boat?

PMID- 1401655
TI  - Lactation performance study raises questions.

PMID- 1401656
TI  - Getting to the roots of cross-cultural counseling.

PMID- 1401657
TI  - Nutritional ergogenics: help or hype? Some 'performance enhancers' may leave
      marathoners running on empty.

PMID- 1401658
TI  - Nutrition labeling: in search of clarity.

PMID- 1401659
TI  - Functional roles of today's public health nutritionist.
AB  - This study found that functional roles of public health nutritionists in eight
      southeastern states differed significantly on the basis of education, dietetic
      registration status, years of experience, and type and level of service. Subjects
      (n = 992) were mailed a 95-item questionnaire with three parts: demographic,
      professional practice, and grant-writing experience. Results based on a 59%
      response rate indicated that most of the 14 functional roles studied were
      practiced in accordance with guidelines presented in Personnel in Public Health
      Nutrition for the 1980's. Only two roles, counselor and educator, were performed
      somewhat inconsistently. Personnel with bachelor's degrees did have more
      counseling responsibilities than those with more advanced degrees. However,
      nonregistered dietitians also had more counseling responsibilities than did
      registered dietitians. Direct care providers had fewer educator responsibilities
      than did personnel with administration/management job responsibilities. All
      personnel reported research responsibilities that increased with advanced
      education, training, years of experience, and type and level of service. We found
      that beyond-entry-level personnel had more administrative and policy-setting
      responsibilities, which is consistent with The American Dietetic Association's
      Role Delineation for Registered Dietitians and Entry-Level Dietetic Technicians
      (1990). We conclude that, with the exceptions of the counselor and educator
      roles, public health nutrition practice is consistent with personnel guidelines.

PMID- 1401660
TI  - Development of financial management competencies for entry-level and advanced
      level dietitians.
AB  - The major purposes in this study were to develop a list of financial management
      competencies for entry- and advanced-level dietitians, determine hospital
      foodservice directors'/chief dietitians' (practitioners) perceived importance of
      these competencies at both levels of practice, and determine educators' perceived
      importance of these competencies at the entry level. Drawing from the literature
      and the judgment of eight experts, we developed a list of 50 financial management
      competencies. Written questionnaires that included importance scales for the
      competencies were mailed to (a) practitioners in a random sample of 1,500 member
      hospitals of the American Hospital Association and (b) directors of Plan IV/V,
      Approved Preprofessional Practice, and Dietetic Internship programs. Response
      rates were 34% for the practitioners and 47% for the educators. Practitioners
      rated 8 competencies as important or very important for entry-level dietitians
      and 26 as important or very important for advanced-level dietitians.
      Practitioners rated all competencies higher for advanced-level dietitians than
      for those at the entry level, and educators rated all competencies higher than
      did practitioners. Content areas, identified by factor analysis, were similar for
      both levels of practice. Our findings indicate that emphasis in undergraduate and
      practice programs should be given to the eight competencies identified by
      practitioners and educators as most important. Our results also may be used for
      development and evaluation of graduate and continuing education programs and for
      specialty certification in foodservice management.

PMID- 1401661
TI  - More effective nutrition label formats are not necessarily preferred.
AB  - An experimental design was used to compare performance and preference for five
      nutrition label formats. Four performance measures--accuracy and false-positives
      in identifying nutrient differences, time required, and correctness in judging
      which product was more nutritious--were derived from a product-comparison task. A
      sample of 1,460 food shoppers over 18 years old was recruited by a shopping mall
      intercept method. Results of the study demonstrated that preferences and
      performance do not necessarily agree. The Control format, which had no nutrition
      profile information, performed the best but was liked the least. The Adjectival
      format, which provided nutrition profile information in the form of descriptive
      adjectives, was the most preferred. Results also showed that listing Daily
      Reference Values or nutrition profile aids increased preference but either did
      not affect performance or decreased it, depending on the specific aid and
      performance measure. Formats that some subjects liked for having adequate
      information others disliked for being hard to use. Formats that some subjects
      liked for being easy to use others disliked for having inadequate information.
      Age, education, and race were related to all of the performance measures except
      judgment of relative nutrition. Only gender was related to preference. Results of
      the study are useful as guidance for the development of consumer education
      materials.

PMID- 1401662
TI  - Parental and professional perceptions of problems associated with long-term
      pediatric home tube feeding.
AB  - We surveyed 24 caregivers of children fed by gastrostomy tube to identify day-to
      day problems encountered in home enteral nutrition. In a second survey, 21
      respondents cross-validated the problem list by rating how often they experienced
      each problem and how difficult each problem was to manage. Problems related to
      social functioning, recreational activities, and family functioning were rated by
      caregivers as the most frequent and difficult. We asked 11 pediatric feeding
      specialists to rate the same problems based on their perceptions of the frequency
      and severity of problems experienced by caregivers. Moderate agreement was found
      between professional and caregiver ratings, although professionals generally
      rated problems as more common and difficult than did the caregivers.
      Additionally, positive relationships were found between caregiver ratings of
      common gastrostomy-tube problems and general levels of stress in the home. Data
      suggest that problems identified by caregivers as most common and difficult are
      often in the social rather than the medical realm. A broadly based family
      assessment that focuses on medical and social aspects of home enteral nutrition
      may maximize nutritional benefits for the patient as well as improve general
      family functioning and reduce stress in the home.

PMID- 1401663
TI  - Nutrition labeling of raw fruit, vegetables, and fish.
AB  - In response to certain requirements of the Nutrition Labeling and Education Act
      of 1990 (the 1990 amendments), the Food and Drug Administration (FDA) developed a
      voluntary nutrition labeling program for the 20 most frequently consumed raw
      fruit, vegetables, and fish in the United States. FDA used data on retail sales
      and food consumption to identify which foods to include in the program and
      developed guidelines for retailers to use in setting up the labeling program in
      their stores. FDA provided interim nutrition labeling data for retail use. These
      data are to be revised and updated at least every 2 years. A representative
      sample of 2,000 grocery stores will be used to assess compliance of retailers
      with the nutrition labeling guidelines. Substantial compliance with the
      guidelines is defined as compliance by 60% of the 2,000 stores.

PMID- 1401664
TI  - Feeding the ultraendurance athlete: practical tips and a case study.
AB  - With the rising popularity of ultradistance sports events lasting from 6 to 24
      hours or multiple days, athletes are consulting registered dietitians for
      specialized dietary advice. Many dietitians, however, lack experience with these
      types of events. This article provides basic guidelines ffor fueling the
      ultradistance athlete. The goals are to maintain normal hydration and blood
      glucose levels, which can be done by enforcing programmed drinking (approximately
      250 to 500 mL/15 minutes, depending on the athlete's sweat rate and environmental
      temperature) and programmed eating (1 to 1.5 + g of carbohydrate per kilogram of
      body weight per hour, depending on the athlete's acceptance of and tolerance to
      solid and/or liquid foods during exercise). Athletes who compete longer than 6 to
      8 hours should consume adequate electrolytes, particularly sodium (approximately
      1 g/hour) through either sports drinks or foods. These guidelines are applied to
      a case study of the 1991 women's winner of the Race Across America, a 2,930-mile
      biking event.

PMID- 1401665
TI  - Lower height of lacto-ovovegetarian girls at preadolescence: an indicator of
      physical maturation delay?

PMID- 1401666
TI  - Contemporary ergogenic aids used by strength/power athletes.

PMID- 1401667
TI  - Adequate energy intake and improved prealbumin concentration as indicators of the
      response to total parenteral nutrition.

PMID- 1401668
TI  - Effectiveness of videotaped dietary instruction for patients hospitalized with
      cardiovascular disease.

PMID- 1401669
TI  - A pilot weight control program for Hispanic women.

PMID- 1401671
TI  - Declaration of Olympia on nutrition and fitness.

PMID- 1401670
TI  - Comparison between food choices of working adults and dietary patterns
      recommended by the National Cancer Institute.

PMID- 1401672
TI  - Mammography and Papanicolaou smear use by elderly poor black women. The Harlem
      Study Team.
AB  - OBJECTIVE: To describe factors related to the use of mammography and Papanicolaou
      smears in low-income women aged 65 or more years to guide development of future
      interventions. DESIGN: A cross-sectional survey. SETTING AND PATIENTS: Elderly
      Black women attending a public hospital medical clinic. MEASUREMENTS: Information
      obtained in a face-to-face interview of a random sample of patients. RESULTS:
      Four-hundred and forty-five women (94%) consented to be interviewed; 74% reported
      a mammogram, and 85% reported a Papanicolaou smear in the past, although these
      early-detection tests were not obtained with any regularity after age 65.
      Concordance between self-reported screening use and blind chart review was more
      than 90%. The major reasons for non-use of both screening tests were that a
      physician hadn't recommended them or that the women didn't know they needed them.
      Levels of knowledge about breast and cervix cancer were low; 68% believed bumping
      or bruising the breast caused cancer, and only 25% knew that cancer risk
      increased with advancing age. In logistic regression models, health status,
      provider type, perceived benefit, life satisfaction, and knowledge of test
      intervals were each significantly associated with mammogram use. Age, health
      status, education, perceived susceptibility and benefit, life satisfaction, and
      knowledge of test intervals were independently related to Pap use (P < .05).
      CONCLUSION: This study illustrates that elderly, poor, minority women who are
      regular health-care users do use mammography and Pap smear screening services.
      Incorporating screening into routine primary care and physician and patient
      education could enhance the use of early cancer detection procedures in this age
      group.

PMID- 1401674
TI  - The relationship between low vision and performance of activities of daily living
      in nursing home residents.
AB  - OBJECTIVE: To explore the link between low vision and Activities of Daily Living
      (ADL) performance in cognitively intact nursing home residents. DESIGN: Survey.
      SETTING: A non-profit geriatric long-term care facility. SUBJECTS: 21 males, 82
      females, aged 66-98. MEASURES: Survey of 103 nursing home residents. ADL
      functioning assessed via Maryland Appraisal of Patient Progress (MAPP); medical
      data collected through chart review; ophthalmological data obtained through
      dilated eye examination by an ophthalmologist. RESULTS: In comparison with
      residents having good vision (n = 52), a significantly greater proportion of
      residents with low vision (n = 51) were dependent on caregivers for performing
      ADLs (eg, toileting, transferring, washing). Residents with low vision had
      significantly more eye pathology (eg, cataracts, age-related macular
      degeneration) than did residents with good vision. There were no significant
      differences between groups with regard to presence of musculoskeletal problems
      (eg, arthritis) or number of medical conditions (eg, cardiovascular disorder,
      cerebrovascular accident). CONCLUSIONS: There is a strong link between low vision
      and ADL disability in nursing home residents. Moreover, ADL dependency is
      significantly related to the presence of eye disorders.

PMID- 1401673
TI  - Screening for depression in hospitalized elderly medical patients: taking a
      closer look.
AB  - OBJECTIVE: To re-examine the test characteristics of the Geriatric Depression
      Scale (GDS) and the Brief Carroll Depression Rating Scale (BCDRS) in elderly
      medical inpatients, simulating the procedure followed by clinicians when using
      screening instruments. DESIGN: Masked comparison of GDS and BCDRS with
      psychiatric interview. SETTING: Durham VA Medical Center. PARTICIPANTS: 109
      consecutively admitted persons aged 70 or over. MEASUREMENTS: Screening by a
      social worker using GDS and BCDRS on day one, followed the next day by an
      investigator's structured psychiatric interview to determine the presence of
      major depressive disorder (MDD). RESULTS: By this method, the sensitivity and
      specificity of the GDS (cutoff 11) were 82% and 76%, respectively; for the BCDRS
      (cutoff 6), they were 73% and 79%. Among those with a negative test, the
      likelihood of MDD dropped from an a priori probability of 10% to an a posteriori
      probability of 3% with the GDS and 4% with the BCDRS. Among those with a positive
      test, the likelihood of MDD was 27% for the GDS and 28% for the BCDRS. Excluding
      patients with cognitive impairment (MMSE < or = 25) only slightly improved test
      characteristics. CONCLUSION: These estimates are considerably below those
      reported in earlier studies where concordant screening, two-stage screening, or
      other methods have been utilized and may impact the decision whether or not to
      screen for depression using these instruments.

PMID- 1401675
TI  - Exporting a successful influenza vaccination program from a teaching hospital to
      a community outpatient setting.
AB  - PURPOSE: To assess whether we could export a successful multifaceted influenza
      vaccination program from an academic medical center to a community setting.
      DESIGN: Pre/post study using concurrent control groups. SETTING: Clinics in a
      staff model Health Maintenance Organization (HMO). One urban and one suburban
      clinic were chosen as intervention clinics, while two similar clinics were
      selected as control clinics. PATIENTS: All patients aged 65 and over enrolled in
      the four clinics. INTERVENTIONS: An informational mailing to patients, a standing
      order policy allowing nurses to administer vaccine, a vaccination reminder on
      daily appointment lists, and availability of walk-in visits for vaccination.
      Patients in the control clinics received usual care. MEASUREMENTS: Vaccination
      rates were determined using a validated postcard survey of 150 randomly selected
      patients at each clinic both at baseline (1988-89) and after the intervention
      (1989-90). RESULTS: The baseline vaccination rates ranged from 51.4% to 74.6%,
      with nearly all vaccinations taking place at the HMO. In one intervention clinic,
      the vaccination rate improved from 56.4% to 72.3%, P = 0.01. In the other, the
      baseline rate was 74.6% and did not change significantly after the intervention.
      There was no change in the vaccination rate in the control clinics after the
      intervention period. CONCLUSIONS: An influenza vaccination program that combines
      several organizational interventions may be successfully exported from an
      academic to a community setting and may serve as a useful model for others.

PMID- 1401676
TI  - The lateral slump sign as an indicator of infection in the elderly.

PMID- 1401677
TI  - Public-private partnerships: the Connecticut model for financing long-term care.
AB  - Responses to the growing crisis in long-term care financing have included efforts
      to negotiate partnerships between the private and public sectors for the purpose
      of developing innovative models for long-term care insurance. One such set of
      models has been encouraged by support from the Robert Wood Johnson Foundation's
      "Long Term Care Insurance Program" grants. The Connecticut Partnership for Long
      Term Care uses a cooperative approach to encourage the development of private
      sector long-term care insurance products that are integrated with Medicaid
      eligibility determinations. The Connecticut model is described, accompanied by a
      history of its development, and a comparison is made with other models currently
      under consideration by national policy analysts.

PMID- 1401678
TI  - Iatrogenic illness in hospitalized elderly people.

PMID- 1401679
TI  - Assisted suicide is not voluntary active euthanasia.

PMID- 1401680
TI  - Morbidity, disability, and health status of black American elderly: a new look at
      the oldest-old.
AB  - There are over 2.5 million black Americans aged 65 and over living in the United
      States today, including some 258,000 persons aged 85 years and over. The post
      World War II baby boom within the US black population should ensure that the
      numbers of persons aged 65 and over will increase into the 21st Century. If
      present trends continue, it is projected that the current population of black
      elders will also age. This means that the numbers of black persons aged 85 and
      over will also increase. Data from both national surveys and population-based
      community studies concerning the health and well-being of black elders are now
      becoming available. This report presents information concerning self-reported
      health status, chronic disease prevalence, disease-risk-factor prevalence,
      measures of physical functioning, and nursing home utilization rates for age
      groups within the black population aged 65 years and over. The availability of
      such data should lead to the development of targeted interventions designed to
      lessen impairment and prolong independent living.

PMID- 1401681
TI  - Geriatric care approaches in health maintenance organizations.
AB  - The objective of this project was to describe geriatric care provided under
      Medicare-risk contracts in HMOs with established Medicare programs. These
      findings provided the basis for an invitational workshop, sponsored by the
      National Institute on Aging and the Robert Wood Johnson Foundation, to formulate
      a research agenda for geriatric care in HMOs. The case study method involved site
      visits to seven HMOs by a physician with expertise in geriatrics, a managed care
      specialist, and a program development specialist. Representatives from the HMOs
      included senior executive officials, physicians recognized for providing and
      promoting geriatric care, research and program development staff, and various
      clinical staff including pharmacists, geriatric nurse practitioners, nurses, and
      social workers. The most frequently encountered geriatric care programs were
      categorized by the following six objectives: (1) identifying high risk patients,
      (2) assessing multi-problem patients, (3) treating multi-problem patients, (4)
      rehabilitating patients following acute events, (5) reducing medication problems,
      and (6) providing long-term care and home health care. Unique programs identified
      from these site visits included screening methods for new enrollees, approaches
      to comprehensive geriatric assessment, use of skilled nursing facilities for
      intensive rehabilitation and postacute care, and drug profiling and review.
      Utilization of geriatric nurse specialists and programs aimed at coordination
      with social services were pervasive in many of these HMOs. Workshop participants
      proposed several research and demonstration projects in all six areas. Overall
      consensus emerged that HMOs with Medicare-risk contracts provide a valuable
      setting for experimentation in geriatric care. Given the current health policy
      emphasis on managed care and capitated payment methodologies, geriatric care
      research in HMOs should be a high priority.

PMID- 1401682
TI  - Of depression, anecdote, and prejudice: a confession.

PMID- 1401683
TI  - The Connecticut model for financing long-term care: a limited partnership.

PMID- 1401684
TI  - Tetanus-diphtheria immunizations in a nursing home population.

PMID- 1401685
TI  - The relationship between cancer and Alzheimer's disease.

PMID- 1401686
TI  - Coexistence of Alzheimer's disease and diabetes mellitus.

PMID- 1401687
TI  - Depression in the elderly: effect on patient attitudes toward life-sustaining
      therapy.
AB  - OBJECTIVE: To determine the effect of depression on preferences for life
      sustaining therapy in older persons. DESIGN: A survey comparing depressed, older
      veterans and a similar, but non-depressed, control group. SETTING: A 490-bed
      Veterans Affairs teaching hospital. PATIENTS: Medical inpatients over 65 years of
      age were potential subjects. Patients who were in intensive care, cognitively
      impaired, unable to communicate, abusing alcohol or drugs, or unable to return
      for outpatient care were excluded. Ninety-five eligible subjects (29%) refused to
      participate. Depressed subjects scored >14 on the Geriatric Depression Scale
      (GDS) and were diagnosed as depressed by a psychiatrist who was blind to the GDS
      results. Complete data were collected on 50 depressed and 50 control subjects.
      MAIN OUTCOME MEASURES: A self-administered questionnaire quantified patients'
      preferences regarding life-saving interventions in their current state of health
      and in four hypothetical scenarios of serious illness. RESULTS: Depressed
      subjects desired fewer interventions than control subjects in their current
      health and in hypothetical scenarios with a good prognosis (P < or = 0.05). There
      were no differences between groups in poor prognosis scenarios. However,
      depression did not explain more than 5% of the variance in decision-making in any
      situation. In good prognosis scenarios, subjects' assessment of quality of life
      was the most powerful predictor of desire for life-saving interventions,
      accounting for 9%-17% of the variance (P <0.01). CONCLUSIONS: These results
      suggest that depression is associated with treatment refusal in situations with a
      good medical prognosis. Depression, however, is only a weak predictor of
      treatment refusal. Further research is needed to define which patients would
      accept medical treatment if effectively treated for depression.

PMID- 1401689
TI  - Community-acquired bacteremia in the elderly: a prospective study of 121 cases.
AB  - OBJECTIVE: To describe community-acquired bacteremia in the elderly and correlate
      clinical and laboratory findings with outcome. DESIGN: Prospective study of
      consecutive cases. SETTING: Large community-based teaching hospital. PATIENTS:
      One hundred and twenty-one elderly patients aged 65 to 89 years, seen between
      February 1, 1986 and January 31, 1988. MAIN OUTCOME MEASURES: Bacteriological
      cultures, symptoms and signs, laboratory findings, and mortality. RESULTS: Gram
      negative organisms accounted for 65 (54%) cases and Gram-positive organisms for
      47 (39%) cases, while nine (7%) cases were polymicrobial. E. coli (39%),
      Klebsiella sp. (8%), S. pneumoniae (14%), and S. aureus (12%) were the most
      commonly isolated organisms. The overall mortality was 38%. A poor prognosis was
      associated with confusion as a presenting symptom (P < 0.0003), hypotension (P <
      0.0003), and inappropriate or delayed treatment (P < 0.02). A good prognosis was
      associated with E. coli as the pathogen (P < 0.0003) and prompt, appropriate
      antibiotic therapy. CONCLUSION: Community-acquired bacteremia in the elderly has
      a high mortality rate. Early recognition and prompt, appropriate treatment are
      critical in reducing the mortality.

PMID- 1401690
TI  - 49th annual scientific meeting of the American Geriatrics Society and the 13th
      annual scientific meeting of the American Federation for Aging Research.
      Washington, D.C., November 14-18, 1992. Abstracts.

PMID- 1401688
TI  - The effect of geriatric evaluation and management on Medicare reimbursement in a
      large public hospital: a randomized clinical trial.
AB  - OBJECTIVE: To study the effect of a geriatric evaluation and management program
      on health care charges and Medicare reimbursement. DESIGN: Prospective randomized
      controlled trial during a 1-year study period. SETTING: Large medical school
      affiliated public hospital in an urban community. SUBJECTS: Patients at least 70
      years old admitted to the medicine service were screened and randomized into two
      groups of 100 patients each. INTERVENTION: Patients randomized to the
      experimental group underwent initial comprehensive geriatric evaluation and once
      discharged from the hospital were enrolled in a geriatric care management and
      treatment program. The control group received usual care only. The major
      intervention of this study was in outpatient long-term care. MAIN OUTCOME
      MEASURE: Total charges for services billed to Medicare Part A and Part B and
      total Medicare reimbursement. The Medicare charge and reimbursement data were
      obtained by use of the Medicare Automated Data Retrieval System, a linked
      Medicare Part A and Part B utilization file. RESULTS: Total charges and
      reimbursement were greater for the control group but not significantly so. Subset
      analysis revealed significantly greater inpatient charges (P < 0.03) and Medicare
      reimbursement (P < 0.005) for the control patients and a greater likelihood of
      utilization of home health care services in the experimental group (P < 0.01).
      CONCLUSION: A geriatric evaluation and management program appeared to shift
      utilization and Medicare expenditures from inpatient services to home health care
      services. There was no evidence that the experimental program resulted in
      increased expenditures for Medicare. In selected populations, geriatric
      evaluation and management programs may contribute to cost containment.

PMID- 1401691
TI  - Shoe sole thickness and hardness influence balance in older men.
AB  - OBJECTIVE: To test the hypothesis that shoes with thick, soft midsoles, such as
      modern running shoes, provide better stability in older individuals than those
      with thin-hard midsoles. In addition, we examined the relation between footwear
      comfort and stability and stability when barefoot. DESIGN: Randomized-order,
      cross-over, controlled comparison. SETTING: Subjects were drawn from an internal
      medicine practice. PARTICIPANTS: A random sample of 25 healthy men, minimum age
      60 years. Additional selection criteria were absence of disabilities influencing
      ability to walk and lack of history of frequent falls. MEASUREMENTS: Balance
      failure frequency, which was defined as falls from the beam per 100 meters of
      beam walking when 10 passes were made down a 9 M long balance beam. Comfort
      rating was based on an ordinal scale. RESULTS: Contrary to the hypothesis: (1)
      midsole softness was associated with poor stability (F(2,48) = 17.9, P < 0.0001);
      (2) thick midsoles also provided poor stability (F(1,24) = 7.36, P < 0.01). When
      barefoot, subjects showed 19% higher balance failure frequency than with the
      poorest shoe and 171% greater than the best shoe (t = 5.33, P < 0.0001). Higher
      comfort was generally found in shoe types associated with higher balance failure
      frequency. CONCLUSIONS: For optimal stability, shoes with thin, hard soles are
      preferable for older individuals. Health professionals should exercise caution
      when recommending shoes with thick, yielding midsoles, such as running shoes, to
      unstable elderly individuals. Older men and women with a history of falls or who
      are obviously unstable, should avoid barefoot locomotion.

PMID- 1401692
TI  - Development of scoring criteria for the clock drawing task in Alzheimer's
      disease.
AB  - OBJECTIVE: To investigate the reliability and validity of free-hand clock
      drawings, a frequently used measure of constructional apraxia, in patients with
      Alzheimer's disease. DESIGN: Survey for the purpose of testing reliability and
      validity of a new scale. SETTING: Memory Disorder Clinic at a university
      affiliated hospital in the Upper Midwest. PATIENTS: Forty-six patients were
      diagnosed with clinically probable dementia of the Alzheimer type after a
      dementia evaluation, and 26 normal elderly controls were research volunteers
      without a history of cognitive dysfunction. MEASUREMENTS: Neuropsychological
      tests, dementia-related scales, and clock drawings rated by a new 20-item Clock
      Drawing Interpretation Scale. Reliability measures, correlations, and clustering
      of items in the CDIS. RESULTS: The CDIS had inter-rater reliability (r = .94),
      internal consistence (rtt = .95), and reproducibility over a 6-month interval.
      CDIS scores were significantly correlated with two dementia-related scales and
      all neuropsychological tests and had the highest correlations with other measures
      of constructional apraxia. All but four Alzheimer patients (91%) and none of the
      controls had CDIS scores of 18 or less. CONCLUSION: Clinicians may reliably
      screen patients with Alzheimer's disease with the clock-drawing task, a measure
      sensitive to deficits in constructional apraxia.

PMID- 1401693
TI  - Characteristics of diabetic ketoacidosis in older versus younger adults.
AB  - OBJECTIVE: To describe how diabetic ketoacidosis in those aged 65 or over differs
      from that in younger adults. DESIGN: Retrospective chart review of all adult
      patients with a primary or secondary discharge diagnosis of diabetic ketoacidosis
      (n = 338). SETTING: Three urban teaching hospitals in Milwaukee, WI from January
      1, 1987 to May 31, 1990. PATIENTS: Two hundred twenty cases in 150 patients met
      our criteria for severity of illness to be included in the study. Twenty-seven
      cases were in patients > or = age 65; 193 cases were in patients < age 65.
      RESULTS: The older patients were less likely to have been using insulin before
      hospitalization (55.6% vs 80.2%, P = 0.004) and less likely to have had a prior
      episode of diabetic ketoacidosis (8.0% vs 51.4%, P = 0.001). The presenting
      laboratory data were not significantly different between older and younger
      subjects. There was a trend toward a higher mean insulin dosage to bring the
      patient's blood glucose to < or = 300 mg/dL for those age 65 or older; 69.1 units
      vs 44.9 units (P = 0.06). The time required to obtain a glucose < 300 mg/dL was
      greater in older patients (10.5 vs 7.7 hours, P = 0.01). The average length of
      stay for those age 65 or older was 12.4 days vs 6.7 days (P = 0.001). Thirdly, of
      those age 65 or older, 7% vs 29% of younger subjects had a blood glucose or
      Accucheck < or = 49 mg/dL at some time during their hospital course. The
      hypoglycemic episodes were more likely to be asymptomatic in older patients (P =
      0.03). The mortality rate was 22% for those age 65 or older vs 2% for younger
      subjects (P = 0.001). The mortality rate for those in age groups 60-69 years, 70
      79 years, and > or = 80 years was 8%, 27%, and 33%, respectively. In patients >
      or = 65, mortality was confined to those with coexisting renal disease or
      infection. CONCLUSION: Older patients with diabetic ketoacidosis are less likely
      to have been using insulin before hospitalization. They tend to receive more
      insulin therapy during their acute management, have a longer average length of
      hospital stay, and have a higher mortality rate.

PMID- 1401694
TI  - A pilot study of anabolic steroids in elderly patients with hip fractures.
AB  - OBJECTIVE: To determine the safety and efficacy of the anabolic steroid
      nandrolone in elderly patients with hip fractures. DESIGN: A randomized double
      blind placebo-controlled trial. SETTING: The orthopedic ward of a university
      teaching hospital. PARTICIPANTS: 29 frail elderly females with hip fractures.
      INTERVENTION: Subjects received nandrolone 2 mg/kg (n = 15) or placebo (n = 14)
      by weekly injection for 4 weeks or until discharge. MEASURES: Baseline functional
      status was assessed by the Lawton-Brody ADL and IADL. Hemoglobin, transferrin,
      thyroid-binding prealbumin, albumin, liver function tests, creatinine, weight,
      MAMC, bioelectric impedance, standard anthropometrics and grip strength were
      measured at baseline and weekly intervals. Rehabilitation parameters and length
      of stay were recorded. RESULTS: The placebo and nandrolone groups were similar in
      age, although the control group had slightly higher baseline ADL scores. There
      was no difference between groups in biochemical parameters, anthropometrics, body
      composition, grip strength, rehabilitation end points or length of stay. One
      subject in the nandrolone group had a doubling of AST and was withdrawn from the
      study. CONCLUSIONS: Nandrolone can be given safely to frail elderly subjects with
      hip fractures but is likely to be of minimal benefit at the doses we employed.

PMID- 1401695
TI  - Driving in Alzheimer's disease.
AB  - OBJECTIVE: To determine if the impaired mental skills in Alzheimer's Disease (AD)
      may adversely affect driving ability. DESIGN: Retrospective survey. SETTING: The
      Alzheimer's Clinic of the University of Kansas Medical Center. PATIENTS: We
      interviewed 67 AD patients and their families and compared them with 100 elderly,
      non-spousal controls. MEASURES: The questionnaire was designed to obtain
      information on their driving habits, with emphasis placed on whether they were
      still driving, and the number of accidents per year for the past 10 years.
      RESULTS: Forty-six of the AD subjects had stopped driving because of safety
      concerns expressed by the subjects, their families, or health care providers, and
      two had stopped for other reasons. Only two of the normal controls had stopped
      driving (P < 0.0001, Chi-square test). Over the past 3 years, the 19 AD subjects
      who were still driving had 263.2 motor vehicle accidents per million vehicle
      miles of travel compared with 14.3 for the controls (P < 0.002, Mann-Whitney U
      test) and 5.7 for the general driving population age > or = 55 years (P < 0.05,
      Students one group, two-tailed t test). CONCLUSION: This study suggests that a
      significant traffic safety problem exists in subjects with AD who continue to
      drive. Efforts should be directed to detect patients with AD whose driving
      presents a traffic safety problem.

PMID- 1401696
TI  - Inadequate treatment of depressed nursing home elderly.
AB  - OBJECTIVE: To determine the prevalence of antidepressant drug treatment among
      nursing home elderly with major depression. DESIGN: Survey early and late in
      nursing home stay. SETTING: Sixty Medicaid/Medicare-certified skilled nursing
      homes. PARTICIPANTS: Admission cohort of 5,752 residents age 65 or older in 1976
      through 1983. MEASURES: Chart review by nurse-abstractors of physicians'
      diagnoses, drug used, and alertness rating. Diagnosis of depression equivalent to
      DSM-III-R major depression. RESULTS: Of 868 persons with a diagnosis of
      depression in the medical record, only 10% were treated with antidepressant
      drugs. More received neuroleptics and benzodiazepines than received
      antidepressants, but most (52%) received no psychoactive drug at all. A subset of
      258 depressed persons had positive notations in their records supporting a mental
      status rating of "alert and oriented." Of that subset, only 15% received
      antidepressants. When followed from admission to discharge or end of study the
      prevalence rate of antidepressant drug treatment increased by 4%. CONCLUSIONS: In
      the late 1970's and early 1980's, even when the primary care physician made and
      recorded a diagnosis of depression, most such nursing home residents remained
      untreated, incorrectly treated, or inadequately treated.

PMID- 1401697
TI  - Recurrent unexplained syncope in the elderly: the use of head-upright tilt table
      testing in evaluation and management.
AB  - OBJECTIVE: To investigate the usefulness of head-upright tilt table testing for
      vasovagal episodes in the evaluation and management of elderly patients with
      recurrent idiopathic syncope. DESIGN: Prospective survey. SETTING:
      Electrophysiology laboratory of a university hospital. PATIENTS: Twenty-five
      patients (11 male, 14 female; mean age 73 +/- 6 years) with recurrent unexplained
      syncope and seven control subjects with other causes of syncope (4 male, 3
      female; mean age 70 +/- 4 years). METHODS: Each patient underwent head-upright
      tilt table testing for 30 minutes with or without an infusion of isoproterenol (1
      3 micrograms/min given intravenously) in an attempt to provoke bradycardia,
      hypotension, or both. MAIN RESULTS: Syncope occurred in nine patients (36%)
      during the baseline tilt and in seven patients (28%) during isoproterenol
      infusion (total positives 64%). None of the controls had syncope during the test.
      All of the patients who had positive test results eventually became tilt table
      negative with therapy, and over a mean follow-up period of 24 months, no further
      syncopal episodes have occurred. CONCLUSIONS: Head-upright tilt table testing
      combined with isoproterenol infusion may be a useful tool in the diagnosis of
      vasovagal syncope in the elderly and in the evaluation of preventive therapy.

PMID- 1401698
TI  - Instrumental activities of daily living as a screening tool for cognitive
      impairment and dementia in elderly community dwellers.
AB  - OBJECTIVE: To identify which Instrumental Activities of Daily Living (IADL) are
      related to cognitive impairment, independent of age, sex, and education; to
      assess the performance of an IADL score using these items in screening for
      cognitive impairment and dementia in elderly community dwellers. DESIGN: Survey
      based on the baseline interview of the PAQUID study on functional and cerebral
      aging. SETTING: Community survey in 37 randomly selected parishes in Gironde,
      France. SUBJECTS: Random sample of 2,792 community dwellers aged 65 and over
      (participation rate: 69%). MEASUREMENTS: Two-phase screening: (1) functional
      assessment, Mini-Mental State Examination (MMSE) and DSM-III criteria for
      dementia; (2) in DSM-III-positive patients, NINCDS-ADRDA criteria applied by a
      neurologist. Functional assessment: IADL scale of Lawton and Brody. Criterion
      standards: cognitive impairment: MMSE score lower than 24; dementia: DSM-III and
      NINCDS-ADRDA criteria. RESULTS: Four IADL items are correlated with cognitive
      impairment independent of age, sex, and education: telephone use, use of means of
      transportation, responsibility for medication intake, and handling finances. A
      score adding the number of IADL dependencies has a sensitivity of 0.62 and a
      specificity of 0.80 at the lowest cut-off point (score > 0) for the diagnosis of
      cognitive impairment. The same score at the same cut-off has a sensitivity of
      0.94 and a specificity of 0.71 for the diagnosis of dementia. The prevalence of
      dementia (2.4%) is reduced by a factor of 12 in subjects independent for the four
      IADL. CONCLUSION: The four IADL score could be incorporated into the screening
      procedure for dementia in elderly community dwellers.

PMID- 1401699
TI  - The effect of aging on intact PTH and bone density in women.
AB  - OBJECTIVE: To determine whether age-related bone loss is negatively associated
      with serum intact parathyroid hormone (PTH). DESIGN: Survey. SETTING: University
      hospital outpatient department. PARTICIPANTS: 100 community-dwelling women, age
      18 to 80, recruited as a convenience sample. MEASUREMENTS: Dependent variables-
      bone density at the spine and femoral neck by dual-energy X-ray absorptiometry.
      Independent variables--age, menopausal status (binary) and intact serum PTH by
      Allegro immunometric assay. RESULTS: Post-menopausal women had higher serum PTH
      and lower bone density of spine and femoral neck than premenopausal women. Bone
      density at the spine decreased with age, but this effect was accounted for by
      menopausal state. Bone density at the femoral neck decreased with age even after
      adjusting for menopause. Log PTH was negatively associated with bone density at
      the femoral neck but not significantly at the spine. Multiple regression analysis
      adjusting for age and menopause showed no significant association between intact
      PTH and bone density at the spine or the femoral neck. CONCLUSION: Although this
      study confirmed the rise in intact PTH with age, there is no evidence that this
      is the mediator of age-related bone loss.

PMID- 1401700
TI  - The Mini-Mental State Examination: identifying the most efficient variables for
      detecting cognitive impairment in the elderly.
AB  - OBJECTIVES: To study how well the scoring on each item of the MMSE relates to the
      sum-score when the purpose is to identify persons with cognitive impairment, and
      to identify an equally effective subset of MMSE items for predicting cognitive
      impairment. DESIGN: Retrospective survey of MMSE data for 850 elderly. SETTING: A
      variety of clinical settings. PARTICIPANTS: Mean age 82 years (range 54 to 99),
      74% women. The subjects were of three different categories: geriatric in
      patients, patients living under supervision, and elderly people living
      independently at home. RESULTS: Five of the binomial ("State," "Town," "Name a
      pencil," "Name a watch," "Read and obey") and one of the polychotomous MMSE
      variables ("Learn three words and repeat immediately") had low sensitivity and
      gave high percentages of misclassifications versus the sumscore dichotomized at
      the cut-point 23/24. Univariate logistic regression indicated that the three
      remaining polychotomous variables ("Spell backwards," "Recall three words," and
      "Three-stage command") can be scored binomially. Two factors were identified on
      factor analysis. Logistic regression analysis showed that 12 of the original 20
      items predicted the sumscore dichotomized at 23/24 with only 3%
      misclassifications. Validation against the psychogeriatrician's diagnosis showed
      that this 12-items MMSE derivative performs as well as the full MMSE.
      CONCLUSIONS: Six of the 20 MMSE variables perform poorly regarding sensitivity
      and misclassifications versus the sumscore at cut-point 23/24. Two additional
      items did not contribute to the prediction of a low/high sumscore. The remaining
      12 MMSE items can all be scored binomially and produce a sumscore which is
      equally as effective as the sumscore of the full MMSE when the purpose is to
      identify elderly patients with cognitive impairment.

PMID- 1401701
TI  - The demented elderly in the city of Helsinki: functional capacity and placement.
AB  - OBJECTIVE: To study prevalence, functional capacity, and placement of demented
      patients in a randomly selected population. DESIGN: Survey. SETTING: Random
      sample from population registry of the City of Helsinki. PARTICIPANTS: Nine
      hundred subjects aged 75 years, 80 years and 85-years, 300 in each group.
      MEASUREMENTS: For each participant, we completed a questionnaire for the subject
      and an informant and a functional-capacity scale and Mini-Mental Status
      Examination by a community nurse, including the Clinical Dementia Rating (CDR)
      scale. Subjects with CDR of 0.5 or greater were examined by a neurologist who
      diagnosed the presence or absence of dementia according to DSM-III-R. RESULTS:
      Ninety-three subjects of the 656 whose CDR was known were found to have dementia.
      Three-quarters of them lived in institutions, and they comprised 33%, 60%, and
      68% of all institutionalized patients in the above-mentioned age groups,
      respectively. Community residents suffering from dementia often lived with a
      caring relative and needed many services. A considerable part of the need was not
      met. CONCLUSIONS: In the older age groups, the need for institutional placement
      due to dementia is great. According to our study, it seems unlikely that these
      patients could be cared for in any other way, at least not on a large scale. The
      need for services for home-dwelling patients is also great, and the relatives
      carry a heavy load in taking care of demented patients.

PMID- 1401702
TI  - Measurement of drug compliance by continuous electronic monitoring: a pilot study
      in elderly patients discharged from hospital.
AB  - OBJECTIVE: A pilot study to assess patient compliance with medication by using a
      new measurement technique, continuous electronic monitoring. DESIGN: Survey.
      Compliance monitors were provided to eligible patients at discharge from the
      hospital to measure drug intake behavior prospectively for a period of 3 weeks.
      SETTING: Ambulant patient care after discharge from a geriatric hospital,
      Krankenhaus Bethanien, which is affiliated with the University Clinic,
      Heidelberg. PATIENTS: A consecutive convenience sample of 18 independently living
      elderly patients (median age 76 years) completed the study. The patients were on
      maintenance therapy with cardiac glycosides and/or potassium-sparing diuretics
      prescribed to be taken once daily. INTERVENTION: The monitoring method provides
      information about patients' real timing of drug use by continuously recording
      date and time of openings and closings of the medication containers (monitors).
      In addition to a standard measure, the percentage of prescribed doses taken,
      information about regularity of drug use is obtained. RESULTS: Compliance,
      percentage of prescribed doses taken, was remarkably variable; it ranged from 24%
      to 100%, 95% CI: 62%-84%. Mean compliance declined from the first to the third
      week after discharge, 85% vs 69%, 95% CI: 74%-95% and 56%-81%, respectively (P <
      0.05). Omissions of doses, the predominant pattern of non-compliance, were
      observed in 17 of 18 patients. Regularity of dose timing, as defined by the
      number of interdose intervals within 24 h +/- 15%, varied from 10% to 100%, 95%
      CI: 46%-76%. CONCLUSIONS: Continuous electronic monitoring revealed highly
      variable compliance in patients prescribed maintenance therapy. Even with a once
      daily regimen, persistent and high compliance cannot be assumed. The monitoring
      technique may be of great value to research and, possibly, to practical
      therapeutic management.

PMID- 1401703
TI  - Obstructive uropathy from uterine prolapse: a preventable problem in the elderly.

PMID- 1401704
TI  - Characterization of osteoporosis in a patient with Werner's syndrome.

PMID- 1401705
TI  - Advances in management of hypertension in older persons.
AB  - Recent studies have now demonstrated that it is more important to focus on the
      SBP level than the DBP level in older persons. In addition, recent studies
      indicate that persons over age 80 still derive substantial benefit from treating
      ISH or DH. Also, studies now show that low-dose diuretics have a more favorable
      impact on subsequent coronary heart disease rates than was previously
      demonstrated. Finally, although caution is urged, it is unlikely the J-shaped
      relationship between treated DBP or SBP and subsequent mortality is due to overly
      aggressive treatment of high blood pressure. Table 4 provides the authors'
      guidelines for treating older persons with high blood pressure.

PMID- 1401706
TI  - Geriatric fellowship training: a revisionist proposal.

PMID- 1401707
TI  - Same patients, different systems: clinical implications for the care of the
      elderly.

PMID- 1401708
TI  - Ethnicity and aging.

PMID- 1401709
TI  - Physician awareness of male osteopenia.

PMID- 1401710
TI  - Thermoregulation and Alzheimer's disease.

PMID- 1401711
TI  - Gender differences in physician stress.
AB  - Differences in perceived stressors in medical practice were identified in this
      study of 72 male and female physicians. Although both men and women physicians
      felt pressured by the amount of time demanded by their profession, women had the
      additional pressure of family obligations. Male physicians were most distressed
      by relationships with patients, the inability to cure, and the threat of
      malpractice. Female physicians, on the other hand, were more likely to be
      concerned about the responsibility inherent in the doctor's role. Although
      physicians have many similar attitudes and behaviors because of their
      professional socialization, their reactions to the pressures of medical practice
      are also influenced by sex-role socialization. Norms and traits appropriate to
      each gender affect the way in which male and female physicians experience
      objective conditions in the work environment.

PMID- 1401712
TI  - A vendetta against working mothers published as science in the Canadian Journal
      of Physics: the editor's role.

PMID- 1401713
TI  - Women in academic medicine: perceived obstacles to advancement.
AB  - To investigate perceived obstacles to the advancement of women in academic
      medicine, we sent a questionnaire assessing perceptions of the fairness and
      supportiveness of the academic environment to the 229 female teaching and
      research faculty of the School of Physicians & Surgeons at Columbia University.
      The overall response rate was 85%. Forty-six percent believed that they had not
      had the same professional opportunities as their male colleagues, 52% believed
      that salaries were not equivalent for men and women in similar positions, and 50%
      believed that promotions were awarded in a biased manner. Thirty percent reported
      that sexist behavior was common and that sexual harassment occurred in the
      workplace. Eighty-one percent experienced conflicts between their professional
      and personal lives and most believed that the institution failed to adequately
      address the needs of women with children. This survey indicates that there are
      significant perceived obstacles to the advancement of women in academic medicine
      that must be addressed.

PMID- 1401714
TI  - Before and after Frances Conley.

PMID- 1401715
TI  - Science or backlash?

PMID- 1401716
TI  - Psychoanalytic ecumenism and varieties of psychoanalytic experience.
AB  - Using the metaphor of ecumenism, the current status of psychoanalysis and the
      American Psychoanalytic Association is examined. The dialectical tendencies to
      oppose and to unify are noted in psychoanalytic theory, technique, and practice,
      as well as in the administrative and political life of our organization.
      Fostering tolerance for new hypotheses without sacrificing empirical
      discrimination, and promoting broad participation without lowering standards
      confront us as major tasks demanding continuing vigilance and effort.

PMID- 1401717
TI  - Followup in psychoanalysis: what happens to treatment gains?
AB  - A recent panel (1989) discussed the feasibility and the desirability of
      systematic post-treatment followup study of psychoanalytic patients. In this
      paper, I compare the data bearing on these issues from the Menninger Foundation
      Psychotherapy Research Project, headed by me, and the Boston Institute Project,
      headed by Kantrowitz, and I indicate why their data are neither comparable nor
      adequate enough to warrant the conclusion that their apparent discrepant findings
      -that in the Menninger project outcome at termination tended to be predictive of
      the subsequent followup course, while in the Boston project this was not so--are
      more than chance events. I then present detailed case descriptions of two
      patients from the Menninger project who were quite similar in character and in
      illness structure, had seemingly comparable analytic courses, and similar good
      therapeutic results, but had quite different followup courses, one with further
      consolidation, and the other with regression. I present some of the determinants
      of this difference.

PMID- 1401718
TI  - The differential effect of psychotherapy and psychoanalysis with anaclitic and
      introjective patients: the Menninger Psychotherapy Research Project revisited.
AB  - Analyses of the data from the Menninger Psychotherapy Research Project (MPRP)
      have consistently indicated little difference in the therapeutic outcome between
      patients seen in psychoanalysis and those seen in psychotherapy. Reanalysis of
      the data from the MPRP, utilizing a distinction between two broad configurations
      of psychopathology (Blatt, 1974, 1990a; Blatt and Shichman, 1983), however,
      indicates that patients whose pathology focuses primarily on disruptions of
      interpersonal relatedness and who use primarily avoidant defenses (anaclitic
      patients), and patients whose pathology focuses primarily on issues of self
      definition, autonomy, and selfworth and who use primarily counteractive defenses
      (introjective patients) differ in their responsiveness to psychotherapy and
      psycho-analysis. Based on recently developed procedures for systematically
      evaluating the quality of object representation on the Rorschach, reanalysis of
      the Menninger data reveals that anaclitic patients have significantly greater
      positive change in psychotherapy, while introjective patients have significantly
      greater positive change in psychoanalysis. These statistically significant
      patient-by-treatment interactions are discussed in terms of their clinical
      implications as well as the importance of differentiating among types of patients
      in studies of therapeutic outcome and of therapeutic process.

PMID- 1401719
TI  - Language and the psychoanalytic process: psychoanalysis and Vygotskian
      psychology. II.
AB  - This paper follows our previous one, where we described a psychoanalytic
      conception of language, thought, and internalization that is informed by the
      thinking of Lev Vygotsky. Here, several aspects of the analytic process which
      allow for the understanding of ineffable experiences in the analysand's history
      and the analytic situation are investigated: specifically, primal repression,
      metaphor, and the role of speech in free association. It is suggested that
      Freud's notion of primal repression be revived and redefined as one aspect of the
      descriptive unconscious. Some implications of primal repression for transference
      and resistance are explored. The metaphoric in its broad sense is examined as one
      example of how early dynamic experiences embedded in the process of language
      acquisition can be reached within the clinical situation. It is proposed that an
      understanding of free association is enhanced by awareness of distinctions
      between inner, egocentric, and social speech. The basic rule can be interpreted
      as an invitation for the analysand to use inner speech in collaboration with the
      analyst as best he or she can. Further, the aliveness and degree of
      superficiality of the analysis can be seen as a function of the analyst's ability
      to appreciate the properties of inner speech and foster the conditions in the
      analysis that allow for its unfolding.

PMID- 1401720
TI  - G. C. Lichtenberg: dreams, jokes, and the unconscious in eighteenth-century
      Germany.
AB  - The German physicist and writer Lichtenberg (1742-1799) was well known during the
      nineteenth century as a humorist, thinker, and psychologist. He was also a
      favorite author of Freud, who read him beginning in his teens, quoted him
      frequently, and called him a "remarkable psychologist." Despite this, he has been
      ignored by psychoanalysts and historians of psychiatry alike, and most of his
      writing is still unavailable in English. An introduction to Lichtenberg as a
      psychologist is provided, stressing material dealing with dream analysis,
      association theory, and drives. Relevant excerpts are translated into English.
      Lichtenberg is shown to have insisted upon the need for a systematic and
      rationalistic study of dreams, to have analyzed individual dreams (describing
      them as dramatized representations of thoughts, associations, and even conflicts
      from his own waking life), and to have emphasized the functional link between
      dreams and daydreams. His remarks on drives and commentary on eighteenth-century
      association theory represent a significant practical application, and thus
      refinement, of Enlightenment rationalistic psychology. These achievements are
      assessed in light of Freud's early fascination with him; it is argued that
      Lichtenberg is an example of the relevance of the historical and cultural
      background of psychoanalysis to clinical practice.

PMID- 1401721
TI  - Freudian and Kleinian theory: a dialogue of comparative perspectives. Panel
      report.

PMID- 1401722
TI  - Enactments in psychoanalysis. Panel report.

PMID- 1401724
TI  - Spectral analysis of sympathetic discharge, R-R interval and systolic arterial
      pressure in decerebrate cats.
AB  - In 19 decerebrate and artificially ventilated cats, we analyzed, with a power
      spectral methodology, the variability simultaneously present in R-R interval and
      in thoracic preganglionic sympathetic outflow. R-R interval was characterized, as
      already described in humans and other experimental preparations, by two rhythmic
      components occurring at a frequency of about 0.1 Hz (low-frequency, LF) and at
      one corresponding to respiratory rate (high-frequency, HF) which, in these
      experiments, was set at 0.32 Hz. Two similar rhythmic components were also
      present in the sympathetic discharge. Arterial pressure changes were produced by
      aorta or vena cava flow obstruction in order to produce reflex responses in
      sympathetic activity. Reflex sympathetic excitations induced an increase in the
      LF component of both R-R interval and sympathetic discharge variabilities, while
      the HF components were simultaneously reduced. In contrast, reflex sympathetic
      inhibitions were accompanied by a decrease in LF components of both variability
      signals, while the HF components were simultaneously increased. A significant and
      positive correlation was found between changes in impulse activity and the
      amplitude of LF component of either R-R interval or sympathetic discharge
      variabilities. These data support the hypothesis that the low-frequency component
      of R-R variability can be used as a marker of sympathetic modulation.

PMID- 1401723
TI  - Location and peptide content of pelvic neurons supplying the muscle and lamina
      propria of the rat vas deferens.
AB  - Retrograde tracing and immunohistochemistry have identified the location within
      the rat pelvic plexus of neurons which project to the vas deferens, and their
      neurochemical properties. The fluorescent tracers, Fast Blue and FluoroGold, were
      injected into the wall of the vas deferens and labelled neurons located within
      the ventral part of the major pelvic ganglion (MPG) and the adjacent accessory
      ganglia (AG). Most neurons were located in ganglia ipsilateral to the injection
      site. Noradrenergic neurons were defined as those containing immunoreactivity for
      tyrosine hydroxylase (TH). Five groups of dye-labelled neurons could be
      identified immunohistochemically, noradrenergic neurons containing neuropeptide Y
      (NPY) (60-70%), and four types of non-noradrenergic neurons, NPY-only neurons (5
      10%), NPY neurons containing vasoactive intestinal peptide (VIP) (3-5%), neurons
      containing only VIP (15-25%) and neurons containing galanin (GAL) (2-5%).
      Noradrenergic axons, and axons containing NPY or GAL were primarily located
      within the muscle, whereas most VIP axons were found as a dense plexus within the
      lamina propria. Very few peptide-containing varicose nerve terminals surrounded
      dye-labelled (vas deferens-projecting) pelvic neurons. Thus, no peptide marker
      was found for most of the preganglionic inputs supplying postganglionic neurons
      which project to the vas deferens. These studies have shown that pelvic neurons
      supplying the vas deferens have a discrete location within the rat pelvic ganglia
      and that they comprise at least five neurochemical groups, providing innervation
      to the muscle and lamina propria. The preganglionic connections with these
      noradrenergic and non-noradrenergic (possible cholinergic) pathways, and further
      examination of the role of mucosal innervation remain to be determined.

PMID- 1401725
TI  - Cardiovascular effects of central clonidine in conscious rats after hypothalamic
      lesions.
AB  - The central injection of clonidine (an alpha 2-adrenoceptor agonist) in conscious
      normotensive rats produces hypertensive responses and bradycardia. The present
      study was performed to investigate the effect of electrolytic lesions in the
      anteroventral third ventricle (AV3V) region or in the lateral hypothalamus (LH)
      on the pressor and bradycardic responses induced by central clonidine in rats.
      Mean arterial pressure and heart rate were recorded in sham or AV3V-lesioned rats
      with cerebral stainless steel cannulae implanted into the lateral cerebral
      ventricle (ICV) or LH, and in sham or bilateral LH-lesioned rats with cannulae
      implanted ICV. The injection of clonidine (40 nmol) ICV or into the LH of sham
      rats produced a pressor response (37 +/- 2-48 +/- 3 mmHg) and bradycardia (-45 +/
      10- -93 +/- 6 bpm). After AV3V-lesion (3 and 12 days) or LH-lesion (3 days) the
      pressor response was abolished and a small hypotensive response was induced by
      the injection of clonidine (-1 +/- 3- -16 +/- 3 mmHg). The bradycardia (-27 +/- 6
      -57 +/- 11 bpm) was reduced, but not abolished by the lesions. These results
      show that the AV3V region and LH are important cerebral structures that
      participate in the excitatory pathways involved in the pressor response to
      central clonidine in rats. They also suggest that, in the absence of these
      pressor pathways, the hypotensive responses to central clonidine may appear in
      conscious rats.

PMID- 1401726
TI  - Three-dimensional analysis of systolic blood pressure and R-R interval: proposal
      of self-sounding spiral theory.
AB  - Having noted the findings that the frequency spectrum of fluctuation in blood
      pressure resembles that in R-R interval on ECG, and that both fluctuations are
      continuous time-related changes, we attempted three-dimensional analysis of blood
      pressure, R-R interval and time. The serial values in systolic arterial pressure
      and R-R interval which were simultaneously taken in 17 healthy volunteers (24.8
      +/- 3.5 years old) were later analyzed using a personal computer. When dots of
      systolic pressure and R-R interval were plotted in order in a three-dimensional
      manner, they depicted spiral movements around an imaginary axis. The magnitude
      and angle of dot movement was then expressed quantitatively, by assuming the
      movements as a group of vectors. The vectors were uniformly distributed in four
      quadrants. The directions of the vector's connections were clockwise in about
      75%, while their angles showed no particular tendency. Based on these three
      dimensional morphological features of fluctuations in blood pressure and R-R
      interval, we propose a hypothesis called 'self-sounding spiral theory' for a
      mechanism preserving the cardiovascular homeostasis.

PMID- 1401727
TI  - TCDD (2,3,7,8-tetrachlorodibenzo-P-dioxin) causes reduction in glucose uptake
      through glucose transporters on the plasma membrane of the guinea pig adipocyte.
AB  - A single dose of 2,3,7,8-TCDD (1 micrograms/kg, i.p. injection) resulted in a
      significant decrease in cellular 3-O-methyl-[3H]-glucose uptake by guinea pig
      adipose tissue and pancreas after 24 hours. An in situ tissue culture study in
      which pieces of adipose tissue were incubated with 10(-8)M TCDD showed a time
      dependent decrease in glucose uptake. Reconstitution of adipocyte plasma membrane
      from tested or control animals into artificial liposomes also resulted in this
      difference in glucose uptake. Binding of [3H]-cytochalasin B, a specific
      inhibitor of glucose transporter proteins, was significantly lower in acetone
      ether powder preparations of TCDD-treated adipose tissue than from controls,
      suggesting that the total titer of these proteins is decreased by TCDD. Finally,
      the relevance of these results to glucose or lipid metabolism was tested.
      Lipoprotein lipase (LPL) activity of guinea pig adipose tissue was decreased
      after 8 hours of in situ incubation with TCDD indicating that glucose uptake was
      depressed at an earlier time point. These findings may contribute to a better
      understanding of dioxin-induced "wasting syndrome".

PMID- 1401728
TI  - An immunoassay for metolachlor detection in river water and soil.
AB  - An indirect enzyme-linked immunosorbent assay (EIA) for metolachlor (2-chloro-N
      (2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamid e) detection in
      river water and soil was developed using serum obtained from rabbits immunized
      against the acid of metalaxyl ((N-(2,6-dimethylphenyl)-N-(methoxy-acetyl)-DL
      alanine methyl ester) conjugated to bovine serum albumin. The assay had a linear
      working range from 1 to 50 ng/ml with a mean I50 value of 13.6 ng/ml and a lower
      detection limit of 2.0 ng/ml. Both the mean interwell and interassay coefficients
      of variation were less than 4% over the range of the standard curves for samples
      which had been prepared in phosphate buffered saline (PBS), river water, or soil
      extract. Assay cross-reactivity to the following four structurally related chloro
      acetanilide pesticides were: propachlor (0%), metazachlor (0%), alachlor (23%),
      and metalaxyl (5,000%). Mean recoveries of metolachlor in spiked (2.0 to 32.0
      ng/ml range) PBS, river water, and soil extract were 102%, 103%, and 110%,
      respectively. Soil samples were taken over a 56-d period from field plots treated
      with metolachlor and analyzed by GC and EIA. The correlation coefficient for
      comparison of the two methods was 0.96 with the slope of the linear regression
      line being 0.78. Furthermore, no statistical difference (P less than 0.05) was
      found between the dissipation curves of metolachlor derived from GC data versus
      EIA data.

PMID- 1401729
TI  - Microbial degradation of propoxur in turfgrass soil.
AB  - This study was conducted to determine the degradation rates in turfgrass soil
      over a 12-month period after a single field application of propoxur and to
      isolate microorganisms from the soil capable of degrading the insecticide. Soil
      samples were collected from a turfgrass experimental site near Fort Lauderdale,
      FL one week before the field application of propoxur, and over a 12-month period
      after the field application. Mineralization rates in surface (0-15 cm depth) and
      subsurface (15-30 cm depth) soil samples collected before the field application
      were low. Mineralization in surface and subsurface samples collected 1, 6 and 8
      months after the field application was much higher than for corresponding samples
      collected before the field application. Mineralization in the subsurface samples
      collected 12 months after the field application had reverted back to the similar
      rate for the corresponding sample collected before field application. Half-life
      values (t1/2) for propoxur showed similar trends to the results of
      mineralization. After a single application of propoxur, degradation in turfgrass
      soil was enhanced. Such enhancement lasted less than 12 months for the
      subsurface, but more than 12 months for the surface. A strain of Arthrobacter sp.
      capable of degrading propoxur was isolated from the soil.

PMID- 1401730
TI  - Brain myelination in rats treated with ionizing radiation in utero.
AB  - Effects of ionizing radiation on brain myelination and some physical development
      parameters were studied in laboratory rats (Fisher F-344 inbred strain). Rats
      were treated with three different doses of radiation (150 rad, 15 rad, and 6.8
      rad) delivered on the 20th day of prenatal life. Exposure to 150 rad reduced
      body, brain, ovary, kidney, heart and spleen weights. Prenatal exposure to 150
      rad of radiation reduced the cerebral cortex weight by 22 percent at 30 days of
      age, and 20 percent at 52 days of age which caused a reduction in cerebral cortex
      myelin content by 20 and 23 percent at the ages of 30 and 52 days respectively.
      This dose did not affect the myelin content of the cerebellum or the brain stem,
      or the myelin concentration (mg myelin/g brain tissue) of the cerebral cortex,
      cerebellum, and the brain stem. The cerebral cortex weight of the 15 rad treated
      rats was reduced at the age of 30 days. Exposure to 15 rad, and 6.8 rad did not
      affect either the myelin content or the myelin concentration of these brain
      areas.

PMID- 1401731
TI  - Polydactyly.

PMID- 1401732
TI  - Correction of overlapping second toe deformity: long-term results including a 7
      year follow-up.
AB  - An alternative to joint destructive procedures for the treatment of overlapping
      second toe deformity is presented. This manuscript examines a modification of the
      cartilaginous articulation preservation procedure previously described. A total
      of seven patients, eight feet were evaluated. The follow-up period ranged from 6
      months to 7 1/2 years, with the average of 3 years. Subjective results were very
      satisfactory. Objectively there were complications, but overall, patient
      improvement was noted postoperatively. This study indicates that the procedure
      should be part of the surgeon's armentarium.

PMID- 1401733
TI  - Verrucous carcinoma: epithelioma cuniculatum plantare.
AB  - Verrucous carcinoma is a well-differentiated form of squamous cell carcinoma.
      This tumor has been shown to mimic a variety of other skin lesions with its
      insidious onset and apparently benign course. Early detection and a thorough
      histologic examination of this growth aid in proper diagnosis, treatment, and
      reduction in morbidity. An interesting case history and literature survey are
      presented to facilitate diagnosis and treatment of this rare pedal neoplasm.

PMID- 1401734
TI  - Hallux fractures: diagnosis and treatment.
AB  - The authors present a review of the literature, mechanisms of injury, and
      radiographic presentations of hallux fractures. Sixty cases (64 injuries) were
      reviewed. Recommendations for treating each type of injury are also presented.

PMID- 1401735
TI  - First metatarsophalangeal joint arthrodesis with the Truncated Cone Reamer
      System.
AB  - This manuscript introduces to the podiatric community the Truncated Cone Reamer
      (TCR) System for precise fashioning of the first metatarsal and proximal phalanx
      for a first metatarsophalangeal joint peg-in-hole type arthrodesis. As the name
      of the system suggests, the device reams out a truncated male cone at the
      metatarsal head and a corresponding female cone at the phalangeal base in the
      desired position. There is congruous cancellous bony contact at all apposing
      surfaces of the truncated cone for bony consolidation. The peg-in-hole
      intrinsically confers the arthrodesis stability. The authors present a step-by
      step use of the TCR system, and a 1 year follow-up case study in which the TCR
      system was used as a template.

PMID- 1401736
TI  - Histological study of the phalangeal articular side following Keller procedure
      for hallux valgus.
AB  - Through a histological study, the authors have examined the coating tissue at the
      base of the proximal phalanx of the hallux. This study concerns five females who
      have undergone an operation according to Keller technique, and necessitated a
      reoperation for unsatisfactory results at the first operation. The study proves
      that resection of the phalanx leads, in time, to the formation of a coating
      fibrous cartilage. Such layer tends to reproduce a structure that is similar to
      an articulation, even though missing a hyaline cartilage. This microscopical
      structure supports well the load that is directed along the perpendicular axis of
      the phalanx, preserving, in time, a sufficient gliding capacity between the two
      surfaces, with optimal limitation of the natural wear-out process.

PMID- 1401737
TI  - The modified Scarf bunionectomy.
AB  - The Scarf bunionectomy offers the surgeon the ability to correct a mild to
      moderate intermetatarsal angle with the stability inherent to this procedure.
      When an increased proximal articular set angle is encountered, this procedure
      could previously only address either the increased intermetatarsal angle or the
      increased proximal articular set angle. The authors' modifications will
      incorporate the best attributes of the Scarf, Reverdin, and McBride
      bunionectomies to allow for concomitant correction of the osseous and soft tissue
      components of the hallux abducto valgus deformity. The authors' experience with
      27 of these procedures performed on 15 different patients from 1987 to 1991 is
      presented.

PMID- 1401738
TI  - Fibular regeneration.
AB  - Total regeneration of an osteotomized fibula is rarely reported in the
      literature. An extensive literature review failed to identify a publication
      addressing this specific topic. The following manuscript describes such an event
      where the fibula was used as a source of autogenous bone graft. A case report
      with long-term follow-up is also presented.

PMID- 1401739
TI  - Podiatric considerations of angioleiomyoma.
AB  - Angioleiomyoma is a benign soft tissue tumor that originates from the smooth
      muscle of blood vessels. Such lesions must be differentiated from fibroma,
      lipoma, ganglionic cyst, glomus tumor, neurofibroma, leiomyosarcoma, and
      phlebitis. These masses appear as encapsulated, glistening nodules that
      ordinarily respond well to surgical excision. It will be the intent of the
      present study to review the clinical and histological characteristics of
      angioleiomyomas as they may appear in podiatric practice.

PMID- 1401740
TI  - Intraosseous lipoma of the calcaneus.
AB  - Intraosseous lipomas of the calcaneus are an extremely rare entity and appear
      radiographically very similar to many other lesions affecting the foot. A case
      report followed by a brief discussion of the etiology, clinical, pathologic, and
      radiologic findings is presented. The authors emphasize the importance of
      magnetic resonance studies as a definitive noninvasive diagnostic modality.

PMID- 1401741
TI  - Recurrent tarsal tunnel syndrome.
AB  - The authors review two cases of recurrent tarsal tunnel syndrome. The patients
      had prior surgical tarsal tunnel releases with complete resolution of symptoms
      before ankle injuries resulting in recurrent tarsal tunnel syndrome. Tarsal
      tunnel is reviewed.

PMID- 1401742
TI  - Osteotomies of the great toe.
AB  - Patients are operated on for forefoot problems at an increasingly younger age,
      according to the author's experience. This has resulted in extra articular
      osteotomies of the first phalanx of the great toe, usually associated with other
      forefoot procedures. There exist several indications for these osteotomies. Among
      them are hallux valgus, hallux rigidus, and other forefoot disorders, such as
      rheumatoid diseases. Since 1984, the author has performed 2850 great toe
      osteotomies, allowing him to specify indications, to elaborate osteotomy
      procedures (varisation, derotation, shortening) and to devise appropriate
      implants, including specific staples and compression screws. A great toe
      osteotomy system has resulted in facilitating the execution of this very useful
      procedure.

PMID- 1401743
TI  - Plantar fibromatosis: literature review and a unique case report.
AB  - Plantar fibromatosis represents a relatively uncommon benign lesion of soft
      tissue. It is most often found to invest the central and medial portions of the
      plantar fascia and commonly occurs in conjunction with other fibrous proliferate
      disorders. The authors present a detailed review of the literature concerning
      this usually unencapsulated fibrous growth. A unique case involving a relatively
      large encapsulated mass found to undergo dorsal extension into the plantar
      musculature is also presented.

PMID- 1401744
TI  - Podiatric imaging quiz. Dysplasia epiphysealis hemimelica or Trevor's disease.

PMID- 1401745
TI  - Giant cell tumor of the foot.
AB  - The author discusses giant cell tumor, often a monostotic bone tumor, as it
      affects the lower extremity. The lesion is most common at the ends of long
      tubular bones, and may transform into malignant pathology. Surgical resection
      with or without bone grafting is an accepted technique for treatment. Recurrent
      abnormality is possible, and close follow-up of these patients is recommended.

PMID- 1401746
TI  - Ultrastructural study on experimentally induced ovarian tumors in the rat.
AB  - Ovarian tumors induced by intrasplenic ovarian grafting were studied
      ultrastructurally to obtain the details with particular references to cytoplasmic
      organelles associated with steroid synthesis. The grafted cells were transformed
      ultrastructurally at around 7 months following intrasplenic ovarian grafting, in
      fact, intermediate type of cells were also seen in the grafts at this period. The
      grafted cells before the transformation showed fine structural evidence of
      steroid hormone secretions, as indicated by the presence of abundant smooth
      endoplasmic reticulum, lipid droplets and mitochondria with tubular or vesicular
      criste. After transformation, the cells, however, had no fine structural features
      associated with the production of steroid hormones.

PMID- 1401747
TI  - Preclinical hypogonadism in genetic hemochromatosis in the early stage of the
      disease: evidence of hypothalamic dysfunction.
AB  - We studied endocrine functions at baseline and after TRH and LHRH stimulation in
      a group of 7 young male patients with genetic hemochromatosis (HE) without liver
      damage (i.e. fibrosis and cirrhosis). In five patients endocrine re-evaluations
      after complete iron depletion was also performed. Mean basal testosterone (T),
      FSH, LH and PRL were significantly lower than in controls. Serum T increased
      normally after HCG stimulation. The normal or high increments of LH after LHRH
      stimulation suggest that secretion capacity of LH was intact and that
      hypothalamic dysfunction could be responsible for the preclinical gonadal
      deficiency found in our patients. The response of PRL to TRH indicates that
      secretion capacity of lactotrophs although present, was decreased and did not
      improve after phlebotomy therapy. After iron depletion the two patients with the
      lowest basal T levels showed the highest increments indicating that in the early
      stages of hypothalamic-pituitary damage gonadal dysfunction is still reversible
      in HE patients.

PMID- 1401748
TI  - Secretion of growth hormone releasing hormone in obese children.
AB  - We have evaluated baseline and l-dopa-stimulated peripheral growth hormone
      releasing hormone (pGHRH) secretion in 6 obese pre-pubertal children and in 7 age
      matched controls. Baseline pGHRH levels were no different between obese (36.6 +/-
      9.8 pg/ml, mean +/- SE) and control children (40.6 +/- 10.1 pg/ml).
      Administration of l-dopa (500 mg po) caused a significant increase of pGHRH
      levels in both the obese (65.3 +/- 19.8 pg/ml, p less than 0.05) and the control
      children (84.1 +/- 10.0 pg/ml, p less than 0.003). Mean peak pGHRH levels after l
      dopa were not significantly different between the two groups, whereas mean peak
      GH levels were significantly lower (p less than 0.05) in the obese (7.9 +/- 1.9
      ng/ml) than in the control children (20.5 +/- 4.9 ng/ml). We conclude that
      despite reduced GH secretion, obese children have normal baseline and l-dopa
      stimulated pGHRH levels.

PMID- 1401749
TI  - Evidence for cortisol as the mineralocorticoid in the syndrome of apparent
      mineralocorticoid excess.
AB  - The hypothesis that cortisol is the functioning mineralocorticoid in the syndrome
      of apparent mineralocorticoid excess was tested by suppressing its secretion with
      dexamethasone. The subjects were two siblings with the type 2 form of this
      syndrome in which the defect in the peripheral metabolism of cortisol lies
      predominantly in ring A reduction but not in 11 beta-hydroxy dehydrogenation of
      cortisol to cortisone. Low dosage dexamethasone improved the hypokalemia within
      several days and hypertension was corrected after 3 weeks of treatment.
      Mineralocorticoid manifestations remained in remission during 10 yr of therapy
      with the synthetic glucocorticoid during which normal growth and development were
      restored. The effectiveness of dexamethasone supports the hypothesis that
      cortisol is the functioning mineralocorticoid in the AME syndrome.

PMID- 1401750
TI  - Riedel's thyroiditis associated with Hashimoto's thyroiditis.

PMID- 1401751
TI  - Nursing home elderly. Social-environmental factors.
AB  - 1. Independence, cohesion, and functional health are related to well-being in
      elderly nursing home residents. 2. Nursing home residents may not criticize staff
      due to fear of a withdrawal of support. 3. Social support provided by visitors
      outside the nursing home may decrease the need for social support from sources
      inside the nursing home.

PMID- 1401752
TI  - Failure to thrive: a growing concern in the elderly.

PMID- 1401753
TI  - Working together: collaboration among HCWs and families in long-term care.

PMID- 1401754
TI  - Nursing research: threats to reliability and validity in gerontology.

PMID- 1401755
TI  - Cardiac assessment of the elderly client.

PMID- 1401756
TI  - HCFA regulations for nurse's aides.

PMID- 1401757
TI  - Perception of knowledge what administrators and assistants know.
AB  - 1. Nurse administrators are responsible for the delivery of health care in long
      term care settings, and it is nursing assistants who provide the majority of care
      meeting the basic needs of elderly in these settings. 2. A difference in
      knowledge perception exists between nurse assistants and nurse administrators on
      information needed by nurse assistants in the home care and nursing home
      settings. 3. Nurse assistants would benefit from expanded nurse assistant
      training programs that would include not only the physical, but also the
      psychological and legal needs of the elderly. 4. Improving the knowledge base and
      the competencies of nurse assistants would improve quality of care in long-term
      care settings.

PMID- 1401758
TI  - [Medical and ethical problems posed by the prenatal diagnosis of distal absence
      of a limb].
AB  - Eight cases of distal amputation of limb are reported. The diagnosis were made by
      ultrasound scans at 18-25 weeks of amenorrhea. In all cases, according to the
      French law, our team of fetal medicine refused the therapeutic terminations of
      pregnancy requested by the parents. The therapeutic terminations of pregnancy
      were achieved by another unit of fetal medicine in France, or in another country.
      These reported cases address many questions about the aim of fetal medicine
      (therapeutic terminations of pregnancy or treatment of infants), the place of the
      parents request in the decision, the different decision arguments, and the
      variations in the decision between different fetal medicine crew facing to
      similar prenatal diagnosis.

PMID- 1401759
TI  - [Limited lumpectomy combined with peroperative curietherapy for conservative
      treatment of breast cancer].
AB  - Lumpectomy together with axillary clearance and radiotherapy is a good
      alternative to Patey's operation for treating early cancers of the breast. In any
      case it has not been definitely worked out how much should be removed. In certain
      patients not much needs to be removed, in other larger areas of tissue need to be
      excised. We present our technique for carrying out limited lumpectomy which is
      carried out at the same time as radiation therapy making it possible to perform a
      less radical clearance. The results in the first 17 patients we have followed up
      with a mean of 4.5 years are very encouraging. There was only one local
      recurrence; this was some distance away from the area of the lumpectomy. The
      limits for the method are determined by the examination that is carried out on
      the margins that have been removed and on the availability of a team comprising
      surgeon, histopathologist and radiotherapist.

PMID- 1401760
TI  - [Bilateral breast tuberculosis: a case report. Review of the literature].
AB  - We report a case of bilateral tuberculosis of the breast that presented as masses
      and where the diagnosis could only be made from the histology. The outcome was
      good following antibiotics and antituberculous treatment. Tuberculosis of the
      breast is a very rare infection. The incidence of the disease is 0.025% of all
      disease of the breast treated surgically. The basis of treatment at the present
      time is antituberculous antibiotic treatment and surgery for any residual masses.

PMID- 1401761
TI  - [Ovulation induction by endogenous LH released by the administration of an LHRH
      agonist after follicular stimulation for in vitro fertilization].
AB  - Sixty-seven patients whose ovulation was stimulated following a protocol of
      Clomiphene Citrate/HMG in order to carry out in vitro fertilisation were divided
      randomly in to two groups. In the first group ovulation was provoked by giving
      10,000 IU HCG IM, but in the other group ovulation was provoked by releasing
      endogenous LH after the administration of Triptoreline in a dose of 0.1 mg in a
      dose subcutaneously three times in one day at 8 hour intervals. The number of
      oocytes recovered, cleavage and embryo transfer were compared between the two
      groups over 48 cycles. The number of conceptions was statistically significantly
      higher in the group that had triptoreline (28%) as compared with 17.4%
      pregnancies in the other group (p less than 0.01). These figures confirm that the
      endogenous LH surge provoked by giving an LHRH agonist can cause adequate final
      oocyte maturation. This property which is associated with a very low risk of
      hyperstimulation, should make it possible to stimulate ovulation when it is not
      used for IVF and so replace the usual injection of chorionic gonadotrophins.

PMID- 1401762
TI  - [The use of Fogarty's catheter for salpingoplasties in laparoscopic surgery].
AB  - Nowadays new techniques of laparoscopic surgery make it possible to carry out
      fimbrioplasties and salpingostomies with results as good as those obtained by
      microsurgery. We describe a new use for the Fogarty catheter as a means of
      traction and for demonstrating the ampulla and the fimbrial end of the tube. The
      pneumatic balloon of the end of the catheter is blown up in the tubal ampulla.
      This makes it possible to bring the tube close to the laparoscope which makes it
      possible to carry out precise precise maneuvers with such degrees of enlargement
      as make it like a form of microsurgery. This kind of procedure helps in these
      delicate and difficult operations.

PMID- 1401763
TI  - [Vulvar sebaceous epithelioma].
AB  - A-77-years old woman had a solitary ulcerated tumor on her vulva present for one
      year. It proved, on histologic examination, to be a sebaceous epithelioma of 1.5
      cm wide because of a peripheral area with less differentiated cells, excess of
      mitoses and slight invasiveness. To the authors' knowledge this is the first
      sebaceous epithelioma documented in this region. Previously have been described
      one sebaceous hyperplasia and two sebaceous carcinomas, one of them eight years
      after hemicolectomy for adenocarcinoma of the colon (Torre-Muir syndrome).

PMID- 1401764
TI  - [Pelvic echinococcosis in women. Two case reports].
AB  - The purpose of this report of two cases of pelvic hydatid disease is to recall
      the aetiology and pathogenesis of this endemic condition in Morocco. We point out
      that because it gives rise to many different clinical signs it is difficult to
      diagnose accurately but if the appropriate blood tests are carried out in every
      case with a pelvic mass the diagnosis could not be missed. It is important to
      treat effectively this condition which can compromise both the gynaecological and
      obstetrical future of the patient and that can have serious repercussions
      extending to the upper urinary tract. The authors, too, show how important it is
      to follow up these cases after operation in order to spot recurrences.

PMID- 1401765
TI  - [Laparoscopic surgery versus laparotomy. Comparative analysis of stress markers].
AB  - The place of laparoscopic surgery continues to increase in the field of surgery
      in our specialty. Although the advantages would seem to be obvious, it seemed to
      us interesting to quantify, if possible, the parameters of operative stress and
      compare laparoscopic surgery with conventional surgery. Markers studied are
      Prolactin, Cortisol, Adrenaline, Nor-Adrenaline, Dopamine and the Beta
      Endorphins. The only marker that shows any difference in the two procedures in
      our study is Beta-Endorphin which is significantly less raised in laparoscopic
      surgery directly after the operation (p less than 0.01). This was very specific
      for pain, which is one of the benefits of this technique and shown in this
      parameter which confirms the clinical impression. The curves of the changes in
      the different markers have been analysed and discussed.

PMID- 1401766
TI  - [Are there still indications for an abdominal hysterectomy? 340 cases].
AB  - This retrospective study of 340 hysterectomies carried out abdominally concern
      cases only where the pathology was benign and strictly limited to the body of the
      uterus. This has made it possible to review the 240 cases carried out for
      fibroids (70.6%), 63 for simple endometrial hyperplasia (18.5%), 28 for
      adenomyosis (8.2%) and 9 for atrophy of the endometrium (2.6%). We looked for
      lesions that could have been treated laparoscopically among these pathologies:
      submucous fibroids with a diameter of less than 4 cms and where the uterus was
      less than 10 cms in height and weighted less than 200 g, simple endometrial
      hyperplasia (the height of the uterus less than 10 cms and the weight less than
      200 g, adenomyosis (uterus less than 10 cms in height and less than 200 g
      weight), this last criteria still "debatable", We found that 110 lesions were
      selected because they could have been treated conservatively. This means that
      32.5% where there seemed to have been indications for hysterectomy out of 340
      cases, could have been treated otherwise. These can be divided aetiologically in
      to: 54 cases of simple hyperplasia of the endometrium (15.9%), 34 cases with
      submucous fibroids (10.6%), 26 cases of adenomyosis (5.9%). If the cases of
      adenomyosis are excluded 90 out of 340 hysterectomies carried out abdominally
      (about a quarter) could have been treated conservatively.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1401767
TI  - [Ureteral and bladder lesions after gynecologic surgery. Value of early
      diagnosis].
AB  - Ureteric and bladder injuries are recognized complications of gynaecologic
      surgery. Efficiency of conservative treatments is directly related to early
      diagnosis. Urinary vaginal fistulas are easily diagnosed in view of post
      operative continuous leakage. Ureteral or bladder obstructions can be quite
      asymptomatic and result in renal destruction or bladder impairment. Reviewing 17
      cases, we emphasize abnormal post-operative pain and biological changes which
      must aware of urologic complications and lead to radiographic studies. Double-J
      stenting or bladder drainage associated with filling of fistula with fibrin
      sealant gives a chance of complete recovery to urogenital fistulas. Percutaneous
      nephrostomy or clean intermittent catheterisation preserves renal or bladder
      function until adequate treatment of obstruction has been defined.

PMID- 1401768
TI  - [Colposcopy in gynecologic cancers. Retrospective study of 192 examinations].
AB  - One hundred and ninety two colposcopic examinations carried out on 183 patients
      of whom 140 had carcinoma of the cervix, 26 carcinoma of the endometrium and 17
      carcinoma of the ovaries were analysed in order to assess the value of colposcopy
      in patients with gynaecological cancer. The mean distance from the edge of the
      anus that was looked at was 45 cms--the range being from--130. Out of all the
      systematic examinations that were carried out before any treatment was started,
      103 were for cervical cancer and among these invasion of the rectal mucosa was
      found in two cases (1.9%). Twelve cases of external pressure on the rectum and 9
      cases of recto-colic polyadenomata (8.7%) of which one was malignant. Out of the
      14 colposcopies that were carried out for carcinoma of the endometrium one case
      of rectal invasion was found and one case of external compression. In the 12
      cases of cancer of the ovary 2 were found to have recto-colic spread, 1 external
      compression and 1 malignant polyadenoma. All these cases of spread to the rectum
      and colon were diagnosed in advanced cases (stage III or IV). In the 63
      examinations carried out on follow-up the most common warning sign was a rectal
      discharge and the most commonly found lesion in the rectum was actinomycotic
      inflammation of the rectum. The 5 cases of recurrence in the rectum expressed
      themselves most often by the rectal syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401769
TI  - [Treatment of the pelvis after total pelvic exenteration. Experience of the
      Regional Paul Strauss Cancer Center of Strasbourg].
AB  - Intestinal morbidity after total pelvic exenteration presents usually as
      fistulae. These appear particularly if irradiation has been carried out in the
      pelvis or the abdomen before surgery, and particularly as a result of the types
      of surgery carried out in the emptied pelvis. An analysis of 92 exenterations of
      the pelvis of which 52 were total exenterations led us to look at how treatments
      in the pelvis have evolved technically and to analyse the contribution they have
      made to reducing the number of fistulae and obstructions found as a result of
      this major surgery. Making a "sac" by packing the pelvis as suggested by the
      pioneer of this exceptionally extensive pelvic surgery gradually has been
      replaced by the use of endogenous material such as the omentum and more recently
      by the use of absorbable synthetic materials (vicryl) which give rise to
      progressive reperitonealisation. The authors approve of this last way of dealing
      with the emptied pelvic cavity because the synthetic material is very well
      tolerated clinically and the polyglactine 910 mesh is not predisposed to
      infection when it is used to make a hammock to prevent chronic radiation
      enteritis by holding the small intestines out of the pelvis.

PMID- 1401770
TI  - [Lipid evolution during normal pregnancy].
AB  - We analyzed the relationship between the evolution of pregnancy and the amplitude
      of the lipid disorders in order to evaluate their chronologic transformations.
      This research concerned 83 pregnancies aged between 19-40 years during the 3
      periods of gestation and 31 healthy control women in the same range of age. Our
      results showed an increased triglyceride in the 2nd period and an earlier
      decrease of both, cholesterol, phospholipid and apolipoproteins. These parameters
      showed a progressive increase of their blood concentrations during the 2nd and
      the 3rd period of pregnancy, in an other hand we evidenced a good correlation
      between gestational aged and these variations i.e.: triglyceride and mother's
      weight; this phenomenon could suggest an eventual role of the nutrition and the
      hygienic habitude in the lipid metabolism. The correlation between our observed
      lipid disorders and the mother's age or the parity were not significant.

PMID- 1401771
TI  - [The risks of pyrimethamine-sulfadoxine combination in the prenatal treatment of
      toxoplasmosis].
AB  - Some of the alternative treatments to avoid termination of pregnancy in cases
      where the fetus is affected by toxoplasmosis is to treat it as soon as the
      diagnosis has been made. The authors who already have experience of using
      pyrimethamine with sulfadoxoine (Fansidar) in the post-natal treatment of
      congenital infection, thought after reviewing the literature that this
      association of drugs would be harmless if applied during pregnancy. The principal
      risk that arises in the fetus is the teratogenicity of each of the components of
      pyrimethamine and sulfadoxine and also their associations. In animals
      pyrimethamine can increase the frequency of cleft palates probably because of its
      antifolinic action but there is no formal proof that it is teratogenic in human
      beings. Furthermore, the theoretical risk of karnicerus in the new born using the
      Sulfonamide has not been demonstrated. In the mother the main but rare risk (1 in
      75,000) seems to be for the production of severe skin lesions such as Lyell and
      Stevens-Johnson which could be brought about by sulfonamides, but not
      particularly sulfadoxine.

PMID- 1401773
TI  - [Pregnancy and obesity. A case control study of 140 cases].
AB  - A retrospective study of 70 fat women and 70 women of normal weight was carried
      out to compare their obstetric performance. The patients were assessed before
      pregnancy for corpulence by estimating the body mass index (IMC). Obesity was
      defined by having an index of 30 or above. The mean weight of the obese patients
      at delivery was 142 kgs and of the controls 65.4 kgs. The main risk in obese
      patients is a raised blood pressure (34%); and in spite of this no child showed
      intrauterine growth retardation. The mean weight of the newborn infants was 3.7
      kgs against a mean weight of 3.2 kgs in the control group. Eighteen infants born
      to obese mothers were very heavy (25%). The increase in fetal weight explains why
      the caesarean section rate was three times as high in the obese patients as in
      the control due to disproportion (25%). These differences are statistically
      significant. Neonatal morbidity was similar in the two groups. It is debatable
      whether a slimming diet was worthwhile. All the same calorie intake reduced
      slightly to about 1.800 calories a day together with vitamin supplements is
      advisable. It does not have any ill effect on the fetus.

PMID- 1401772
TI  - [Quadruplet pregnancies: management and obstetric and pediatric outcome].
AB  - Multi-fetal gestations are associated with increased frequency of maternal, fetal
      and neonatal complications. Data on the prognosis of multi-fetal pregnancies are
      of particular importance when the option of selective termination is considered.
      The present study details the obstetric management, neonatal outcome, and follow
      up of seven quadruplet pregnancies in a french university center. The perinatal
      mortality was 250/1000. The neonatal mortality was 214/1000. The incidence of
      respiratory distress syndrome was 38%, bronchopulmonary dysplasia 19% and
      intraventricular hemorrhage 9.5%. Follow-up from one to 16 years shows that no
      child is handicapped. Our specific management for higher order multi-fetal
      pregnancies include early diagnosis, meticulous follow-up, early decrease of
      maternal activity, midwives at home, psychological care, delivery by cesarean
      section and a neonatalogist for each baby at the time of delivery.

PMID- 1401774
TI  - [Monitoring cervical dilatation by impedance].
AB  - Several different physics procedures have been tried to mechanize the recording
      of partograms. Can a measure of impedance of tissue Z using potential difference
      V, according to Ohm's law V = Z1, and 1 is a constant, be correlated with a
      measure of cervical dilatation using vaginal examination? This was our
      hypothesis. The tissue impedance meter was made to our design and applied
      according to a bipolar procedure. Our work was carried out on 28 patients. 10
      patients were registered before labour started in order to test the apparatus and
      to record the impedance variations without labour taking place, and 18 patients
      were registered in labour to see whether there was any correlation. The level of
      impedance in the cervix without labour was 302.7 Ohms with a deviation of 8.2.
      Using student's t tests it was found that there was a significant correlation (p
      less than 0.001) in four measurements between the impedance measure and measures
      obtained by extrapolating the degrees of dilatation calculated from vaginal
      examination. This is a preliminary study in which we have defined the conditions
      that are necessary to confirm these first results and to further develop the
      method.

PMID- 1401775
TI  - [Placenta praevia percreta with bladder invasion: a case report].
AB  - The authors report a rare case of placenta praevia percreta with bladder invasion
      giving rise to the need to carry out an emergency hysterectomy in order to stop
      the bleeding. The literature when analysed showed the possible outcome of this
      complication in a woman who had already had a caesarean section and who had
      placenta praevia that required a second caesarean. In this situation it is almost
      inevitable that a hysterectomy has to be carried out to stop the bleeding. The
      hysterectomy should be a total hysterectomy but this can be difficult because of
      the invariable "fusion" that takes place between the uterus and the posterior
      wall of the bladder. What has to the done bladder can range from simple closure
      of a hole in the bladder to ureteric diversion with reimplantation of the ureter
      depending on how badly the bladder has been invaded. In our case after a sub
      total hysterectomy had been carried out with simple closure of the bladder, it
      was necessary to re-operate to treat a fistula between the bladder and the
      cervix.

PMID- 1401776
TI  - [Malaria and pregnancy].

PMID- 1401777
TI  - Developmental changes of ventricular fibrillation threshold and spontaneous
      defibrillation in young dogs.
AB  - This study was conducted to systematically investigate whether induction and
      maintenance of ventricular fibrillation in the canine heart, change with age
      during the early postnatal development. Forty-eight mongrel puppies from seven
      litters, were randomly selected for size and studied at weekly intervals from 1-6
      weeks for determination of ventricular fibrillation threshold and incidence of
      spontaneous defibrillation. Another fourteen mongrel puppies 8-11 weeks old and
      10 adult dogs were similarly studied. Ventricular fibrillation threshold
      increased progressively with age up to the eighth week (VFTmA = 8.38 + 2.67 wk
      0.134.wk2, r = 0.995) and thereafter reached a plateau, which was not
      significantly different from the ventricular fibrillation threshold of adult dogs
      (26.5 +/- 2.2 mA). In contrast, the high incidence of spontaneous defibrillation
      at early age decreased rapidly between second and fourth week and became rare
      thereafter, (%SDF = 281.e-0.60wk, r = 0.94. This rapid drop could not be
      explained by the increase in mean body weight, which did not change significantly
      during this early period (BWkg = 0.59.e0.23wk, r = 0.97). Our findings suggest
      first, that the vulnerability of the neonatal dog heart to electrical induction
      of ventricular fibrillation decreases progressively during early age. Second,
      that spontaneous defibrillation decreases precipitously between the second and
      fourth week of age, a change not sufficiently explained by the modest body weight
      gain during that time. Thus, it appears that about the third week of age
      ventricular vulnerability to fibrillation and ability to defibrillation reach a
      critical point, where lethal arrhythmias may become both inducible and
      sustainable, to result in death.

PMID- 1401778
TI  - Oxygen consumption is maintained in fetal sheep during prolonged hypoxaemia.
AB  - Experiments were conducted in 12 chronically-catheterized pregnant sheep to
      examine the effect of prolonged hypoxaemia secondary to the restriction of
      uterine blood flow on fetal oxygen consumption. Surgery was performed at 115 days
      gestation to place a teflon vascular occluder around the maternal common internal
      iliac artery and for insertion of vascular catheters. Following a 5-day recovery
      period, uterine blood flow was reduced in 6 animals for 24 hours and in 6
      animals, the occluder was not adjusted. Fetal arterial PO2 decreased from 19.9 +/
      2.0 mmHg to 12.8 +/- 2.0 mmHg and 11.0 +/- 2.0 mmHg at 1 and 24 hours
      respectively in the experimental group and did not change the control group.
      Fetal pH decreased from 7.34 +/- 0.01 to 7.25 +/- 0.03 and 7.29 +/- 0.02 at 1 and
      24 hours of hypoxaemia respectively. Fetal arterial lactate concentrations
      remained elevated throughout the experimental period with maximum concentrations
      of 6.6 +/- 2.1 mmol/l being present at 4 hours compared to 1.3 +/- 0.2 mmol/l
      during the control period. Umbilical blood flow increased from 186 +/- 19
      ml/min/kg to 251 +/- 39 ml/min/kg at 1 h of hypoxaemia and returned to 191 +/- 21
      ml/min/kg at 24 h. In association with the progressive fall in oxygen delivery to
      the fetus, oxygen extraction increased from 0.33 +/- 0.04 to 0.43 +/- 0.04 and
      0.54 +/- 0.05 at 1 and 24 hours, respectively. Overall oxygen consumption by the
      fetus remained unchanged from control values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401779
TI  - Pulsatile oxytocin administered to ewes at 120 to 140 days gestational age
      increases the rate of maturation of the fetal electrocorticogram and nuchal
      activity.
AB  - Spontaneous, long lasting epochs of myometrial contractility, contractures, occur
      throughout the majority of pregnancy in sheep. Contractures are temporally
      related to a switch in fetal electroencephalogram (ECoG) patterns from low to
      high voltage. In late gestation, fetal ECoG increases in voltage. We have
      previously suggested that contractures may influence fetal ECoG maturation. In
      the present study, we hypothesized that a sustained increase in the frequency of
      myometrial contractures in pregnant sheep at 120-140 days gestation would
      accelerate maturation of the fetal ECoG. Five pregnant ewes were pulsed with
      oxytocin 600 microU.kg-1.min-1 intravenously for five minutes in every 30 minutes
      from 127.8 +/- 1.5 days gestational age for a minimum of six days. Six control
      ewes received pulses of saline. Fetuses of all eleven ewes were instrumented with
      bilateral electrodes to record fetal ECoG and nuchal muscle activity. Fetal high
      voltage (HV) ECoG increased in amplitude in both groups but the rate of increase
      was faster in the fetuses of ewes receiving oxytocin. There were no differences
      between the two groups in the duration of HV ECoG. The percentage increase in the
      amount of time the fetal nuchal muscles were active compared with the baseline
      day before infusion was only significant in the oxytocin infused group on the
      first day of oxytocin infusion. These findings support the hypothesis that
      myometrial activity during pregnancy has the capacity to influence fetal neural
      development.

PMID- 1401780
TI  - Interrelationships between plasma insulin-like growth factor-I (IGF-I)
      concentrations and plasma sex hormone levels in the growing male guinea-pig.
AB  - The aim of the present study was to determine the influence of androgens on
      Insulin-like Growth Factor-I (IGF-I) release at puberty in male guinea-pigs.
      After the animals were orchiectomised (CX) or sham-operated (SO) at the end of
      weaning, plasma testosterone (T), dihydrotestosterone (DHT) and IGF-I levels were
      measured by RIA at the 4th (W4), 8th (W8) and 12th (W12) week after delivery.
      Body weight (BW) was recorded before sampling at each stage of the experiment.
      Body growth was maximal between W4 and W8 for both SO (+97%) and CX (+84%).
      However SO were heavier than CX at W8 and W12. In SO, a surge of plasma IGF-I
      levels was observed between W4 and W8, concomitantly to the increase of androgen
      levels (IGF-I: +86%, P less than 0.01; T: +190%, P less than 0.001; DHT: +18%; P
      less than 0.01). Significant correlations between IGF-I, T, DHT and BW were found
      only from W4 to W8 but not from W8 to W12. In CX, IGF-I levels were higher than
      in SO at W4 (+72%, P less than 0.01) and at W12 (+39%, P less than 0.01). A surge
      of IGF-I levels (+47%, P less than 0.01) was also observed but was delayed
      compared to SO (between W8 and W12 vs W4 and W8). BW and IGF-I levels were
      significantly correlated during this period. Because the surge of IGF-I levels
      may occur even in absence of gonads, these results give evidence that the
      increases in IGF-I and androgens at puberty were independent in guinea-pigs
      during this period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1401781
TI  - Effect of aminophylline on the pulmonary and systemic hemodynamic response to
      group B beta-hemolytic Streptococcus and leukotriene D4 in newborn lambs.
AB  - Aminophylline, a methyl xanthine, has been used for many years in the treatment
      of apnea of prematurity and bronchospasm. Aminophylline relaxes smooth muscle
      through several proposed mechanisms. We hypothesized that aminophylline might be
      effective in relaxing preconstricted pulmonary vascular smooth muscle and would
      be ideally suited for clinical trial in babies with pulmonary hypertension. To
      test this hypothesis, the haemodynamic response of chronically instrumented
      newborn lambs to injections of heat-killed Group B beta-hemolytic Streptococcus
      (GBS) and leukotriene (LT) D4, potent pulmonary vasoconstrictors was compared
      before and after pretreatment with a clinically therapeutic dose of intravenous
      aminophylline. GBS (10(9)cfu) significantly increased pulmonary arterial pressure
      130%. LTD4 (1.0 microgram/kg) significantly increased pulmonary arterial pressure
      142% and systemic arterial pressure 23% and decreased cardiac output 47%.
      Aminophylline did not significantly affect the baseline variables or alter the
      pulmonary or systemic haemodynamic response to either stimuli. Therefore, it is
      unlikely that aminophylline will be clinically useful in the treatment of babies
      with persistent pulmonary hypertension whose etiology is infectious or
      leukotriene-mediated.

PMID- 1401782
TI  - Architecture of selected muscles of the arm and forearm: anatomy and implications
      for tendon transfer.
AB  - The architectural features of twenty-one different forearm muscles (n = 154 total
      muscles) were studied. Muscles included the extensor digitorum communis to the
      index, middle, ring, and small fingers, the extensor digit quinti, the extensor
      indicis proprius, the extensor pollicis longus, the flexor digitorum
      superficialis, the flexor digitorum profundus, the flexor pollicis longus, the
      pronator quadratus, the palmaris longus, the pronator teres, and the
      brachioradialis. Muscle length, mass, fiber pennation angle, fiber length, and
      sarcomere length were determined with the use of laser diffraction techniques.
      From these values, physiologic cross-sectional area and fiber length/muscle
      length ratio were calculated. The individual digital extensor muscles were found
      to be relatively similar in architectural structure. Similarly, the deep and
      superficial digital flexors were very similar architecturally, with the exception
      of the small finger flexor digitorum superficialis, which was much smaller and
      shorter than the rest of the digital flexors. The brachioradialis and the
      pronator teres had dramatically different architectural properties. While the
      masses of the two muscles were nearly identical, the muscles had significantly
      different predicted contractile properties based on their different fiber
      arrangement. The brachioradialis, with its long fibers arranged at a small
      pennation angle, had a physiologic cross-sectional area that was only one third
      that of the pronator teres, with its short fibers that were more highly pennated.
      Using these architectural data and the statistical method of discriminant
      analysis, we provide additional information that might be useful in the selection
      of potential donor muscles to restore thumb flexion, thumb extension, finger
      extension, and finger flexion.

PMID- 1401783
TI  - How musculotendon architecture and joint geometry affect the capacity of muscles
      to move and exert force on objects: a review with application to arm and forearm
      tendon transfer design.
AB  - This commentary reviews musculotendon architecture and the relation between
      architectural parameters and the force, speed, and excursion capacity of
      musculotendon units. It is hoped that this review will help provide the framework
      within which to appreciate the importance of the data presented by Lieber et al.
      Muscle fiber pennation hardly affects musculotendon output of forearm and hand
      muscles. Instead, physiologic cross-sectional area and muscle fiber length affect
      force capacity and speed and excursion capacity, respectively. How muscles with
      equal mass can have different force, speed, and excursion capacities is
      explained. Since the moment arm of a muscle (the shortest distance from the
      musculotendon unit to the joint center of rotation) transforms muscle output into
      musculotendon output, it is shown why the capacity for a muscle to exert force on
      an object, as during grasping, is directly proportional to its moment arm and why
      the range of joint movement and speed over which muscles exert force is inversely
      proportional to the moment arm. Finally, tendon, being not stiff in forearm and
      hand musculotendon units, also affects their output. Criteria are given for
      designing tendon transfer reconstructions from architectural data and moment arm
      data to best replicate the biomechanical function of the replaced muscle. To have
      the same capacity for imparting movement to objects and exerting force on them,
      the donor muscle should have the same moment arm/physiologic cross-sectional area
      product, the same fiber length/moment arm ratio, and the same tendon
      length/muscle fiber length ratio as the replaced muscle.

PMID- 1401784
TI  - Architectural design of the human intrinsic hand muscles.
AB  - The architectural features of twenty different muscles (18 intrinsics and 2 thumb
      extrinsics, n = 180 total muscles) were studied. Muscle length, mass, fiber
      pennation angle, fiber length, and sarcomere length were determined. From these
      values, physiologic cross-sectional area and fiber length/muscle length ratio
      were calculated. Intrinsic muscle lengths were relatively similar to one another,
      which we interpreted as representing a space constraint within the hand. However,
      several specialized architectural designs were observed: lumbrical muscles had an
      extremely high fiber length/muscle length ratio, implying a design toward high
      excursion. The first dorsal interosseous and adductor pollicis had physiologic
      cross-sectional areas comparable to those of extrinsic muscles and much greater
      than those of the other intrinsic muscles. The interosseous muscles had
      relatively high physiologic cross-sectional areas with low fiber length/muscle
      length ratios, suggesting their adaptation for high force production and low
      excursion. Taken together, these observations illustrate the underlying
      structural basis for the functional capacities of the intrinsic muscles.

PMID- 1401785
TI  - Extensor pollicis longus opposition transfer.
AB  - A new technique of opposition transfer uses the extensor pollicis longus tendon,
      which is sectioned just proximal to the metacarpophalangeal joint of the thumb,
      routed through the interosseous membrane, advanced subcutaneously across the
      anterior surface of the forearm but deep to the extensor pollicis brevis tendon,
      and sutured to its distal stump with a 1 cm overlap. This technique differs from
      th at of Riley et al. in several significant ways, although the same motor is
      used. Experience in 35 cases has yielded good or excellent results in 31
      instances.

PMID- 1401787
TI  - A new tendon transfer for ulnar clawhand: use of the palmaris longus extended
      with the palmar aponeurosis.
AB  - A new tendon transfer for ulnar paralytic clawhand, in which the palmaris longus
      with distal extensions of the palmar aponeurosis is passed under the transverse
      carpal ligament and fixed to the A-1 pulley of the small and ring fingers, is
      described. Advantages of the procedure are that there is no loss of function and
      free tendon grafts are not needed.

PMID- 1401786
TI  - Modified technique of sternomastoid transfer for elbow flexion.

PMID- 1401788
TI  - Restoration of elbow flexion in root lesions of brachial plexus injuries.
AB  - A retrospective review of 87 patients with loss of elbow flexion secondary to
      root injuries of the brachial plexus was carried out. Results of nerve grafting,
      direct nerve transfer with the intercostal nerve, or tendon transfer were
      analyzed, and treatment recommendations were developed. Nerve transfer provided
      good or excellent results for injuries that included avulsion of the C5 and/or C6
      roots. Nerve grafts were used successfully in cases of single or combined
      ruptures of C5 and C6. Tendon transfers provided good or excellent results in C5
      C6 or C5-C7 avulsions, where nerve grafting was not possible and transferable
      muscles had good strength. Somatosensory evoked potentials were necessary to
      demonstrate nerve root avulsions in cases in which the roots appeared ruptured on
      visual inspection.

PMID- 1401790
TI  - An Automated Tactile Tester for evaluation of cutaneous sensibility.
AB  - The Automated Tactile Tester (ATT) is a computer-controlled device designed to
      measure patients' cutaneous perception of touch, vibration, temperature, and
      pain. The ATT provides repeatable and precise control of the amplitude, rate of
      application, and duration of stimuli. Threshold values for skin indentation
      (touch), high- and low-frequency vibration, pinprick (sharpness), warmth, and two
      point discrimination were obtained with the ATT from the fingers of 62 normal
      subjects. Manual monofilament and two-point discrimination tests were also
      performed on the same subjects. All the tests with the ATT, except pinprick,
      showed a statistically significant increase in threshold with age. There were no
      significant differences attributable to the hand or digit tested or the sex of
      the subject. These data were used to derive age-adjusted criteria for normal
      sensory function in the glabrous skin of the fingers. Thresholds were found to
      remain within normal limits when these subjects were retested at various time
      intervals. We conclude that the ATT provides repeatable and reliable measurements
      of sensory function in the skin and has potential application in the diagnosis
      and evaluation of compression and other peripheral neuropathies.

PMID- 1401789
TI  - Intercostal nerve transfer of the musculocutaneous nerve in avulsed brachial
      plexus injuries: evaluation of 66 patients.
AB  - Intercostal nerve transfer is a well-established and effective technique for
      irreparable avulsed brachial plexus injuries. Between 1987 and 1989, 66 patients
      with brachial plexus injuries were treated by means of intercostal nerve transfer
      to the musculocutaneous nerve, with or without nerve grafts to obtain elbow
      flexion. The results were evaluated. Five clinical signs--(1) induction of chest
      pain by squeezing of biceps, (2) proximal biceps contraction, (3) distal biceps
      contraction, (4) active elbow flexion against gravity, and (5) active elbow
      flexion against weight--were identified and used as a guide for functional
      recovery. The overall success rate with motor function of grade 4 or more was
      67%. The motor results were better in 1989 (81%) because of greater familiarity
      with the anatomy and improved surgical technique. The important factors in
      obtaining a good result are (1) early exploration (less than 5 months after
      trauma), (2) use of three intercostal nerves, (3) mixed nerve-to-mixed nerve
      coaptation, (4) nerve repair without grafts and under no tension, and (5)
      shoulder stability.

PMID- 1401791
TI  - Evaluation of nerve compression with the Automated Tactile Tester.
AB  - The Automated Tactile Tester (ATT) was used to measure threshold values for
      trapezoidal skin indentation (light touch), low- and high-frequency vibration (50
      and 150 Hz), pinprick (sharp-dull transition point), warming (temperature
      awareness), and two-point discrimination in 61 patients with symptoms of median
      nerve compression at the wrist. We compared these data with values obtained in
      the same patients with manual monofilament tests, manual two-point discrimination
      measurements, and electrophysiologic nerve conduction studies. The ATT detected
      abnormal sensation in 71% of the hands tested, nerve conduction velocity was
      abnormal in 44% of the cases, and the manual tests indicated abnormality in 42%
      of the hands. The most indicative single test among those included in the present
      study for detecting sensory abnormality in these patients was threshold to a 50
      Hz vibration administered by the ATT. We conclude that the ATT is a sensitive
      tool for the diagnosis and evaluation of compressive peripheral neuropathy and
      may allow objective documentation in a higher percent of patients than do more
      traditional testing methods.

PMID- 1401792
TI  - Establishment of carpal contents/canal ratio by means of magnetic resonance
      imaging.
AB  - Magnetic resonance imaging (MRI) was used to determine cross-sectional areas and
      volumes of carpal canals and carpal canal contents in five cadaver specimens in
      an assessment of the reliability of MRI for establishing contents/canal ratios.
      Volumes of the carpal canals and their contents were accurately calculated from
      MRI with a previously described correction factor (0.8161) for carpal tunnel
      volumes and a calculated correction factor (1.078) for carpal tunnel contents
      volume. There was no significant difference between laboratory-measured or MRI
      calculated ratios from either volumes (p = 0.86) or surface areas (p greater than
      0.79). Cross-sectional area contents/canal ratios were significantly higher (p =
      0.0001) at the level of the distal aspect of the hook of the hamate (0.54) as
      compared with those at the level of the distal radial styloid (0.42) and proximal
      metacarpals (0.44). MRI provides an effective and reliable means of determining
      contents/canal ratios from both cross-sectional area and volume calculations.

PMID- 1401793
TI  - Longitudinal study of median nerve sensory conduction in industry: relationship
      to age, gender, hand dominance, occupational hand use, and clinical diagnosis.
AB  - As part of a longitudinal study of the cause of carpal tunnel syndrome in
      industry, we evaluated sensory conduction of the median nerve in relation to age,
      gender, hand dominance, occupational hand use, and clinical diagnosis. The
      original 1984 study group consisted of 942 hands of 471 industrial workers, and
      the follow-up study group in 1989 consisted of 630 hands of 316 (67%) of these
      same workers. The palmar segmental stimulation technique was employed, and
      slowing was defined as a maximum latency difference of 0.4 msec or more after
      adjustment for temperature variation. There was no significant change in the
      prevalence of slowing between 1984 and 1989 (23% in 1984, 22% in 1989), and
      slowing was still strongly correlated with increased age but not with gender.
      Slowing continued to be more prevalent in the dominant hand. Slowing was no
      longer correlated in any fashion with occupational hand use. The prevalence of
      probable carpal tunnel syndrome was still strongly correlated with the degree of
      slowing. Age and hand dominance were more important than any job-related factor
      in the prediction of slowing after 5 years.

PMID- 1401794
TI  - Vibration exposure and conditioning lesion effect in nerves: an experimental
      study in rats.
AB  - The effects of controlled vibrations of defined frequency (80 Hz), acceleration
      (32 m/s2 root mean square), and duration (5 hours daily, 2 or 5 days) induced to
      the hind limb of rats on the regeneration potential in the sciatic nerve after a
      test crush lesion were determined. Exposure to vibration induced a marked and
      significant increase in outgrowth length of axons from the crush injury as
      evaluated after 3 and 6 days with the pinch reflex test. This effect was still
      observed 1 month but not 3 months after exposure to vibration. Even such a short
      duration of vibration exposure as 2 days induced an increased length of
      outgrowth. Such a conditioning effect may be due to local changes in the
      environment of the axons or to changes in the nerve cell bodies in the dorsal
      root ganglion. The results indicate that an alarm reaction exists in the nerve at
      a time point where no structural changes are observed in the nerve. By inducing
      such a conditioning lesion to nerve tissue, vibration represents a trauma
      corresponding to a crush lesion or transection of the nerve.

PMID- 1401796
TI  - Biomechanical evaluation of chronic boutonniere reconstructions.
AB  - The magnitudes of the extensor forces generated across the proximal
      interphalangeal joint by the Littler-Eaton, Matev, Hellmann, and Fowler
      reconstructive procedures for posttraumatic chronic boutonniere deformity were
      measured in a laboratory study. The purpose of the experiment was to determine
      whether the mechanical design of a procedure had a significant impact on
      biomechanical performance. Results showed that each method produced adequate
      extensor forces and restored full proximal interphalangeal joint extension. There
      were few statistically significant differences among the procedures for the
      different joint angles and load conditions tested. The data suggest that the
      mechanical designs of these reconstructions are satisfactory for correction of
      the extensor deficit of the deformity. The preoperative condition of the finger
      is probably responsible for the variations seen in clinical results.

PMID- 1401795
TI  - Tendon reconstruction for postburn boutonniere deformity.
AB  - A surgical procedure in which a tendon graft is used to reconstruct the hood of
      the proximal interphalangeal joint for the correction of the postburn boutonniere
      deformity is described. The intent is to use the potential of the lateral bands
      for simultaneous extension of the interphalangeal joints, avoiding their
      excessive palmar displacement. The technique has been employed in 22 fingers with
      satisfactory results, except in the small finger.

PMID- 1401797
TI  - Correction of the severe nonrheumatoid chronic boutonniere deformity with a
      modified Matev procedure.
AB  - Twenty consecutive patients with severe chronic nonrheumatoid deformities were
      treated with a modification of the Matev procedure. Fourteen of the 20 had normal
      passive range of motion preoperatively, with the proximal interphalangeal joints
      lacking 59 degrees of active extension and the distal interphalangeal joints
      hyperextended 17 degrees. In the other six patients with PIP contracture at the
      time of reconstruction, PIP joints lacked 68 degrees of active extension and the
      DIP joints were hyperextended 13 degrees. Follow-up averaged 8 months, and at
      that time the patients with no contracture had an average of 14 degrees/96
      degrees of active motion at the PIP joint and 9 degrees/59 degrees of motion at
      the DIP joint. The group with contracture had an average of 21 degrees/80 degrees
      of active motion at the PIP and 13 degrees/41 degrees of motion at the DIP joint.
      There were 85% good or satisfactory outcomes in the group without contracture and
      67% good or satisfactory outcomes in the group with contracture.

PMID- 1401798
TI  - Index finger pollicization for congenital aplasia or hypoplasia of the thumb.
AB  - Sensation, strength, dexterity, length, and range of motion were evaluated after
      index finger pollicization in 10 patients (14 hands). Diagnoses included
      congenital absence of the thumb (10 hands) and hypoplasia (4 hands). Average age
      at operation was 7 years, and follow-up averaged 9 years. Patients with
      unilateral pollicization averaged 67% grip strength, 60% lateral pinch, 56%
      palmar pinch, and 39% three-point pinch as compared with the normal contralateral
      hand. Manual dexterity averaged 70% efficiency as compared with normal standards
      defined according to age and sex. However, 55% of the patients, when stressed,
      used side-to-side pinch. It was noted that in those patients who used side-to
      side pinch performance averaged 54% of normal standards, compared with 93% in
      patients who used tip-to-tip pinch for prehension.

PMID- 1401799
TI  - Congenital hypertrophy of the thenar eminence with accessory head of the abductor
      pollicis brevis in the forearm.

PMID- 1401800
TI  - Congenital arteriovenous malformation of the finger resulting in cardiac
      decompensation: a case report.
AB  - Congenital arteriovenous malformations of the hand may be hemodynamically
      significant in the neonate. Progressive cardiac decompensation is an indication
      for surgical intervention. The cause and classification of congenital vascular
      lesions of the hand are discussed.

PMID- 1401801
TI  - Radial head dislocations in children with below-elbow deficiencies.
AB  - Two thirds of the children who have below-elbow deficiencies, congenital or
      acquired, have concomitant radial head dislocations. The direction of the
      dislocation depends largely on the length of the residual limb. The dislocation
      does not require specific surgical treatment and rarely necessitates prosthetic
      modification.

PMID- 1401802
TI  - Extension block pinning for proximal interphalangeal joint fracture dislocations:
      preliminary report of a new technique.
AB  - The simple, percutaneous placement of a smooth pin into the head of the proximal
      phalanx creates an extension block, which prevents subluxation of the middle
      phalanx and allows early active flexion of the proximal interphalangeal joint.
      Three case reports involving this new treatment are presented along with a
      detailed description of the technique.

PMID- 1401803
TI  - Misleading fractures after profundus tendon avulsions: a report of six cases.
AB  - From 1986 to 1990, twelve patients were treated for avulsions of the flexor
      digitorum profundus in either the ring or the long finger. Six patients had
      misleading x-ray films because the tendon had retracted farther than the fracture
      pattern had suggested. All of these patients had avulsion fractures from the
      palmar aspect of the distal phalanx. Although the classification of Leddy and
      Packer is very helpful in determining the prognosis for these injuries, the
      fracture patterns are not reliable in predicting the location of the retracted
      tendon end preoperatively. Therefore all flexor digitorum profundus tendon
      avulsions should be surgically repaired as soon as possible.

PMID- 1401804
TI  - Avascular necrosis of the scaphoid: report of three cases treated with a proximal
      row carpectomy.
AB  - Three cases of avascular necrosis of the scaphoid are reported. One patient, who
      was using corticosteroids on a regular basis, had other areas of bone necrosis.
      None of the patients had a history of trauma. All three patients were treated
      with proximal row carpectomy with satisfactory results.

PMID- 1401806
TI  - Thumb interphalangeal joint sesamoiditis.

PMID- 1401805
TI  - Treatment of scaphoid nonunion with casting and pulsed electromagnetic fields: a
      study continuation.
AB  - This article presents a continuation of a study of the treatment of scaphoid
      nonunion with pulsed electromagnetic fields (PEMF) and cast immobilization. Fifty
      four patients were reviewed. The overall success rate for healing has decreased
      since the previous review from 80% to 69%. Proximal pole fractures healed in 50%.
      Success in nonunions with associated radiographic evidence of avascular necrosis
      decreased from 89% to 73%. Although we believe that the indications for use of
      PEMF have not changed significantly, this study suggests that a successful
      outcome with PEMF and casting is less likely than previously reported. We believe
      that until additional clinical studies have further defined the indications,
      treatment protocol, and efficacy of this method PEMF treatment should be a
      secondary alternative to bone-grafting procedures.

PMID- 1401807
TI  - Fifth digit sesamoid fracture with tenosynovitis.

PMID- 1401808
TI  - Salvage for failed implant arthroplasty of the wrist.
AB  - We have had to revise 19 wrist arthroplasties--seven silicone implants and 12
      metal-on-plastic total wrist arthroplasties. Each of the seven silicone implants
      was successfully revised in one operation; the four fusions and three total wrist
      implants were functioning 6 or more years after surgery. Nineteen operations were
      needed to revise the total wrist implants. Four had failed because of loosening,
      six had become unbalanced, and two had become infected. All of the loose
      prostheses eventually required fusion. Four of the unbalanced wrists were
      rebalanced, but two of these patients have pain; the other two cases required
      fusion. One infected wrist required fusion, and one is stable with an implant.

PMID- 1401809
TI  - Evaluation of digital prostheses.
AB  - Fifty-one digital prostheses were made for 33 patients between 1986 and 1988. A
      questionnaire was developed to assess the patients' satisfaction with these
      prostheses and was administered 6 months and 3 years after the prostheses were
      made. The majority of patients requested prostheses for esthetic reasons. While
      they reported satisfaction with the appearance of the prostheses, at 3 years 36%
      of the patients no longer continue to use the prostheses.

PMID- 1401810
TI  - Vascular anatomy of the finger dorsum and a new idea for coverage of the finger
      pulp defect that restores sensation.
AB  - The cutaneous vascular anatomy of the finger dorsum was studied by dissection
      under loupe magnification of 71 fingers from 19 preserved cadaver hands. All
      specimens were injected with red latex or epoxy resin through a cannula in the
      brachial artery to identify the small vessels. The finger dorsum was supplied by
      the terminal branches from the dorsal metacarpal artery around the
      metacarpophalangeal joint. Other areas were nourished by the dorsal cutaneous
      branch from the proper palmar digital artery. There were two or three dorsal
      branches in the proximal phalangeal region and two in the middle phalangeal
      region. On the basis of these findings, we have developed a new method for one
      stage reconstruction of finger pulp defect that restores sensation. Our
      innervated reverse vascular pedicle digital island flap includes the dorsal
      digital nerve and the proper palmar digital artery as a retrograde vascular
      pedicle. We have used the technique in three patients, with excellent results.
      The advantage of this procedure is that it provides a one-stage reconstruction of
      the pulp defect and restores sensation. The disadvantage is that the procedure
      requires neurorrhaphy.

PMID- 1401811
TI  - Palmar advancement flap with V-Y closure for thumb tip injuries.
AB  - The palmar advancement flap with V-Y closure was used in two patients with thumb
      tip injuries. This technique allows more distal advancement of the flap than does
      a conventional palmar advancement flap and does not require skin graft coverage.

PMID- 1401812
TI  - Sodium hyaluronate as an adjunct in adhesion prevention after flexor tendon
      surgery in rabbits.
AB  - Topical application of sodium-hyaluronate (NaHe) has been proposed to decrease
      the formation of adhesions after tendon surgery, but reports published thus far
      have been contradictory. A new test instrument capable of simultaneous
      registration of tensile load, tendon excursion, and joint motion was therefore
      developed and used to evaluate the effect of locally administered NaHe of
      different concentrations and molecular weights on the outcome after tenorrhaphy
      of rabbit hindlimb flexor tendons. Immediately after tenorrhaphy, NaHe or saline
      solution was deposited into the tendon sheath. The functional characteristics of
      the digits were evaluated 15 days after surgery. NaHe with a concentration of 19
      mg/ml and a molecular weight of 6 x 10(6) significantly limited the strength of
      the adhesions formed without impairment of tensile strength. These results
      suggest that the efficacy of NaHe is affected by both the concentration and the
      molecular weight of the NaHe preparation used.

PMID- 1401813
TI  - Controlled mobilization after flexor tendon repair in zone II: a prospective
      comparison of three methods.
AB  - A new controlled-motion program that incorporates dynamic flexion traction to all
      four digits, a short splint leaving the interphalangeal joints free, and a
      nighttime extension splint was prospectively compared with a modification of the
      Kleinert technique and a combination of the modified Kleinert technique and
      passive movements. Each program was applied to approximately one third of 178
      consecutively treated digits with tendon injuries in zone II. The mean total
      active interphalangeal joint range of motion 6 weeks and 1 year postoperatively
      was significantly better and extension deficits were significantly less frequent
      in the digits mobilized with the new program. The postoperative treatment input,
      in terms of frequency of reviews and time spent in therapy sessions, is not
      greater than with more traditional controlled-motion programs. Our results
      indicate that the new program is a safe, reliable, and cost-effective method that
      produces very good results in a general population.

PMID- 1401814
TI  - Results of small-joint arthrodesis: comparison of Kirschner wire fixation with
      tension band wire technique.
AB  - In a retrospective study the results of 203 interphalangeal and
      metacarpophalangeal arthrodeses performed between 1977 and 1990 were reviewed.
      Eighty-three percent of the cases involved severe hand injuries. Two fixation
      techniques were used. During the early period, 143 arthrodeses were performed
      with percutaneous Kirschner wires, combined with either interosseous wiring or
      plaster of Paris. From 1987 to 1990, 60 arthrodeses were performed with the use
      of tension band fixation. In the Kirschner wire group 18% of the patients had pin
      track infections, and in 15% rearthrodeses were necessary. In the tension band
      group 2% of the patients had an infection, and in 5% rearthrodeses were
      performed. Both the infection rate and the rearthrodeses rate were significantly
      lower in the tension band group than in the Kirschner wire group. Judging from
      this study, the tension band fixation technique is the method of choice for
      arthrodeses of the small finger joints.

PMID- 1401815
TI  - Treatment of hand injuries by external fixation.
AB  - Thirty-five consecutive applications of external fixation to the hand, including
      27 acute cases and 8 reconstructive procedures, were studied. In both settings,
      external fixation was used not only for skeletal stabilization but also for
      management of the soft tissues. Twenty of the 22 acute fractures healed, and six
      arthrodeses with interposition bone grafts resulted in fusion. Three septic
      nonunions resolved, and two united successfully. There were no complications. We
      recommend external fixation systems in the hand, and several case reports are
      included in the study to illustrate the various applications.

PMID- 1401816
TI  - Rehabilitation and surgical reconstruction of the upper limb in tetraplegia: an
      update.

PMID- 1401817
TI  - Hand and forearm injuries from penetrating projectiles.
AB  - Compared with other surgical literature published after the Vietnam and Persian
      Gulf wars, hand surgery literature has been relatively void of information
      regarding projectile injury. Wound ballistics research of the past 10 years has
      shown that objective evaluation of tissue disruption is the only valid guide to
      treatment. The hand's anatomy requires hand surgeons to be more careful in tissue
      excision. Hand surgeons, therefore, do not have the luxury of "cutting till it
      bleeds." The purpose of this article is to support the methods that hand surgeons
      have traditionally used and to caution the inexperienced surgeon who may be
      inclined to excise uninjured tissue.

PMID- 1401818
TI  - Classification system for factitious syndromes in the hand.

PMID- 1401819
TI  - Pacinian corpuscle hyperplasia in the hand.

PMID- 1401820
TI  - Ulcerative colitis and Crohn's disease health status scales for research and
      clinical practice.
AB  - We report the development of ulcerative colitis (UC) and Crohn's disease (CD)
      Health Status Scales that improve on existing inflammatory bowel disease (IBD)
      activity measures by their added association with health status. We surveyed 991
      members of the Crohn's and Colitis Foundation of America (CCFA) and analyzed the
      half with greater disease activity (114 UC, 330 CD, ostomies excluded). Our
      analysis strategy involved (a) identification of items that discriminated active
      from inactive disease, (b) factor analysis to reduce the items to clusters
      sharing common symptom relationships, and (c) regression analysis to select those
      variables best associated with a composite measure of health status (health care
      use, daily function, psychologic distress). The factor analyses yielded two
      indexes for UC and CD: "Diarrhea," and "Other GI symptoms" (Cronbach's alpha 0.59
      0.84). The regression analyses for both diseases showed that poorer well-being,
      the Diarrhea index, and dependence on medication for pain were associated with
      poorer health status. For UC, lower educational attainment and lower steroid
      dose, and for CD, the Other GI symptoms index and eye disease, also correlated
      with poorer health status. By design, the UC and CD Scales are better predictors
      of health status than the survey version of the CD Activity Index (CDAI),
      explaining 17 and 21% more of the variance of the health status measure. The
      final UC and CD Health Status Scales can be used in research and clinical care.
      They contain symptom items used to assess disease activity and also correlate
      with health status. Prospective assessment is needed to confirm their accuracy in
      assessing prognosis and treatment response.

PMID- 1401821
TI  - Are tiny polyps important when found on sigmoidoscopy in asymptomatic people?
AB  - To determine the occurrence of synchronous large bowel polyps located proximal to
      the sigmoid, in persons undergoing screening flexible sigmoidoscopy, we examined
      those who had diminutive polyps (less than or equal to 0.5 cm) as the only
      finding in the distal colon by further colonoscopy. One hundred one asymptomatic
      persons (mean age 61 +/- 13 years) had 143 diminutive polyps; a single polyp was
      found in 76%, and 64% of all polyps were located in the rectum. Thirty (21%) were
      hyperplastic and 86 (60%) were neoplastic, including 14 with moderate and one
      with severe dysplasia. The others were inflammatory (five) or unclassified (hot
      biopsy changes or normal mucosa, 14 polyps), and eight were lost before
      processing. Colonoscopy revealed that 16 (16%) of the 101 patients had 21
      additional polyps proximally, mostly less than 1 cm in diameter. These included
      one hyperplastic and 18 neoplastic polyps, and two specimens showed hot biopsy
      changes. Age, histological type, number or location of the index diminutive
      polyps, were not associated with proximal lesions. We question whether immediate
      colonoscopy is justified in asymptomatic patients with only diminutive polyps at
      flexible sigmoidoscopy.

PMID- 1401822
TI  - Liver biopsy under hypnosis.
AB  - Two patients underwent outpatient percutaneous liver biopsy under hypnosis
      without complications. One patient had severe anxiety about the procedure because
      of a previous adverse experience with liver biopsy and the other had a history of
      severe allergy to local anesthesia. Both patients had undergone a session of
      hypnosis at least once prior to the biopsy. One received no local anesthetic and
      the other received 1% lidocaine as a local anesthetic. Both patients were
      completely cooperative during the procedure with the required respiratory
      maneuvers. Both patients stated that they were aware of the procedure under
      hypnosis but described no pain and would be most willing to have the procedure
      done under hypnosis in the future. Hypnosis can be a useful method of preparing
      carefully selected patients for percutaneous liver biopsy.

PMID- 1401823
TI  - The effect of lactulose and lactitol administration on fecal fat excretion in
      patients with liver cirrhosis.
AB  - Mild to moderate fat malabsorption is frequently present in patients with liver
      cirrhosis. We investigated the influence of lactulose or lactitol treatment on
      fecal fat excretion in 18 patients with liver cirrhosis. All patients were Child
      Pugh class A or B and had not taken any therapy that could have affected
      intestinal absorption in the previous months. The dose of lactulose or lactitol
      was individually adjusted to maintain two semiliquid bowel movements per day.
      Steatorrhea was determined before and after a minimum of 7 days, when the
      cathartic effect was stabilized. Treatment with nonabsorbable disaccharides
      induced mild to moderate steatorrhea in 50% of patients. No differences were
      observed between the effects of lactulose and lactitol, but fecal fat excretion
      exceeded 10 g/day in two patients taking lactulose. These findings indicate that
      treatment with nonabsorbable disaccharides may increase fecal fat excretion in
      patients with liver cirrhosis. This factor should be taken into consideration
      when a cirrhotic patient has to take these drugs for a long time.

PMID- 1401824
TI  - Malignant lymphoma of jejunum with common variable hypogammaglobulinemia and
      diffuse nodular hyperplasia of the small intestine. A case study and literature
      review.
AB  - We report a patient with common variable hypogammaglobulinemia and diffuse
      nodular lymphoid hyperplasia of the small intestine complicated by a jejunal
      malignant lymphoma. Immunopathological and histological studies showed a
      polymorphous centroblastic lymphoma with intracytoplasmatic IgM immunoglobulin
      and lambda light chains. Some mucosal nodules separate from the tumor mass showed
      atypical lymphoid cell populations similar to lymphoma cells, suggesting a
      transition between hyperplastic nodules and lymphoma nodules. Four similar cases,
      and six other patients with malignant lymphoma of the small intestine, associated
      with diffuse nodular lymphoid hyperplasia, but without immunodeficiency, have
      already been described. All these cases suggest that nodular lymphoid hyperplasia
      increases the risk of small intestine lymphoma.

PMID- 1401825
TI  - Synchronous cancer of the biliary tract and pancreas associated with anomalous
      arrangement of the pancreaticobiliary ductal system.
AB  - A 58-year-old man on abdominal ultrasonography and CT had an irregularly elevated
      lesion at the neck of the gallbladder and a cyst of approximately 6.5 cm in
      diameter at the pancreatic tail. Percutaneous transhepatic cholangiography
      revealed a 2-cm shadow defect at the neck of the gallbladder and an irregular,
      translucent 30 x 12 mm lesion in the intrapancreatic bile duct. Total
      pancreatectomy and extended cholecystectomy with regional lymph node dissection
      was performed. An anomalous arrangement of the pancreaticobiliary ductal system
      (AAPBD) was demonstrated by postoperative contrast radiography of resected
      specimen. The lesions of the gallbladder and common bile duct were papillary
      adenocarcinoma. In addition, papillary adenocarcinoma was limited almost entirely
      to the mucosal layer of the main pancreatic duct and its branches, from the
      junction of the common bile duct and pancreatic duct to the pancreatic tail. The
      three tumors were not continuous. The cyst at the pancreatic tail was a
      pseudocyst. This case represents synchronous cancer of the gallbladder, common
      bile duct, and pancreas associated with AAPBD.

PMID- 1401826
TI  - Liver failure and the sea-blue histiocyte/adult Niemann-Pick disease. Case report
      and review of the literature.
AB  - Niemann-Pick disease is a metabolic disorder resulting in accumulation of
      sphingomyelin in visceral organs. The adult form (type B) is characterized by the
      sparing of brain involvement, allowing those affected to have a relatively benign
      course. Although the abnormal lipid accumulation in the liver is commonly
      recognized, hepatocellular compromise is extremely rare. We describe a patient
      with adult Niemann-Pick disease who over the course of over 35 years developed
      hepatic failure and portal hypertension, and we review the literature regarding
      hepatic involvement in this rare disease.

PMID- 1401827
TI  - Giant duodenal gallstone presenting as gastric outlet obstruction: Bouveret's
      syndrome.
AB  - In a 91 year old woman with nausea and vomiting, the diagnosis of Bouveret's
      syndrome was considered when a barium meal disclosed a cholecystoduodenal fistula
      and a giant filling defect in the duodenum. Because of her age and underlying
      medical illness, operative therapy was initially deferred. Repeated attempts to
      remove the intermittently obstructing duodenal gallstone endoscopically were
      unsuccessful using both endoscopic retrograde cholangiopancreatography retrieval
      baskets and an endoscopic mechanical lithotripter. The patient was referred for
      definitive operative therapy, and was discharged after a successful and
      uneventful enterolithotomy.

PMID- 1401828
TI  - Inflammatory fibroid polyp of the stomach. Report of three unusual cases.
AB  - Three patients with inflammatory fibroid polyp (IFP) of the stomach underwent
      operation with a diagnosis of submucosal tumor, polyp, and intramural tumor of
      the stomach, respectively. Resected specimens grossly showed a deep ulcer
      accompanied by surrounding upheaval, a sausagelike polyp 6.5 cm long, and a
      pedunculated tumor with a short pedicle, respectively. Histologic examination
      showed that each lesion was typical of IFP of the stomach, with a mixture of
      fibroblasts and thin-walled blood vessels, and further by an intense infiltrate
      of eosinophils. These cases indicate that IFP of the stomach can vary in gross
      appearance. Practitioners and pathologists must remember that not only a polypoid
      lesion, but also a pedunculated or even ulcerated lesion, in the gastric antrum
      may be IFP.

PMID- 1401829
TI  - Histamine/serotonin ratio (H/S ratio): a new scale for determining the degree of
      inflammation in ulcerative colitis.

PMID- 1401830
TI  - NSAID-induced irreversible exacerbation of ulcerative colitis.

PMID- 1401831
TI  - Testosterone and androgen metabolism in pancreatic cancer.

PMID- 1401832
TI  - Levels of carcinoembryonic antigen and carbohydrate antigen (CA19-9) in pure
      pancreatic juice and sera in a patient with occult pancreatic cancer.

PMID- 1401833
TI  - Serum pepsinogen A in atrophic chronic gastritis and in gastric cancer: a
      distinctive difference in behavior?

PMID- 1401834
TI  - Serum levels of gastrin in patients with colorectal cancer.

PMID- 1401835
TI  - Erythromycin: a colonic prokinetic agent?

PMID- 1401836
TI  - N-acetylcysteine in treatment of acetaminophen overdose.

PMID- 1401837
TI  - Problems and controversies in endoscopic survey of the resected stomach.

PMID- 1401839
TI  - In healthy humans the colonic mucosal endogenous prostacyclin content shows a sex
      difference.

PMID- 1401838
TI  - Fatal torsade de pointes occurring in a patient receiving intravenous vasopressin
      and nitroglycerin.

PMID- 1401840
TI  - Syphilitic hepatitis.

PMID- 1401841
TI  - Successful treatment of Clostridium difficile colitis with ciprofloxacin.

PMID- 1401842
TI  - Duodenal perforation by a biliary endoprosthesis: evaluation by hepatobiliary
      scintigraphy.

PMID- 1401843
TI  - Bleeding duodenal lipoma.

PMID- 1401844
TI  - Read my lips.
AB  - The leading hairy edge of the lip is claimed to be related to peptic ulcer
      disease. Implications of this relationship are examined in light of psychiatric
      and probabilistic possibilities.

PMID- 1401845
TI  - Half-mustache--a clue to peptic ulcer?
AB  - In this article, we quantify a clinical observation that non-Ashkenazi Jews
      having a half-mustache on the lower part of their upper lip have a high frequency
      of peptic ulcer and dyspepsia. The prevalence rate for peptic ulcer and dyspepsia
      was 33.6% and 44.9%, respectively, in the study group, compared with 11.2% and
      24.3% in the control group. Although psychological examination was not conducted,
      we hypothesize that subjects who trim their mustache in this manner have
      obsessive and perfectionist characteristics and show features of extroverted
      personality. We speculate that these traits may be contributory to the
      development of peptic ulcer and dyspepsia.

PMID- 1401846
TI  - Age and depression.
AB  - In this study, the relationship between age and depression is analyzed, looking
      for effects of maturity, decline, life-cycle stage, survival, and historical
      trend. The data are from a 1990 sample of 2,031 U.S. adults and a 1985 sample of
      809 Illinois adults. The results show that depression reaches its lowest level in
      the middle aged, at about age 45. The fall of depression in early adulthood and
      rise in late life mostly reflects life-cycle gains and losses in marriage,
      employment, and economic well-being. Depression reaches its highest level in
      adults 80 years old or older, because physical dysfunction and low personal
      control add to personal and status losses. Malaise from poor health does not
      create a spurious rise of measured depression in late adulthood. However, some of
      the differences among age groups in depression reflect higher education in
      younger generations, and some reflect different rates of survival across
      demographic groups that also vary in their levels of depression.

PMID- 1401847
TI  - The costs of sharing: wives' employment and husbands' mental health.
AB  - Although there is general concern about the psychological effects of gender
      stratification, we know relatively little about the particular aspects of
      inequality that affect men and women's mental health. This paper proposes that
      inequalities in power and demands associated with gender are particularly
      consequential for well-being. Previous analyses on married women support this
      perspective: wives' employment is positive for women's well-being to the extent
      that it increases their income relative to husbands and decreases their domestic
      demands, particularly through husbands sharing in domestic labor. The present
      analysis extends the test of this perspective to men by examining the effects of
      wives' employment on husbands' psychological well-being. Results show that
      insofar as it decreases husbands' relative income and increases their share of
      domestic labor, women's employment is negative for husbands' mental health.

PMID- 1401848
TI  - Interactive and higher-order effects of social influences on drug use.
AB  - The study of moderators and higher-order effects of social influences on drug use
      has many implications for theories of health behavior. In the present study, we
      investigated the longitudinal predictive effects of some of the prominent
      moderator variables that represent forms of susceptibility toward social
      influence in teenage drug use. We also studied the possibility that social
      influence may predict drug use in nonlinear (quadratic) forms, consistent with
      theories proposing that threshold or decelerating effects may occur in social
      influences on normatively sanctioned behaviors. Results showed that several of
      the interactive and quadratic predictive effects were significant. The findings
      supported the views that certain moderator variables act as buffers, which either
      protect the individual from social pressures to use drugs, or make the individual
      more susceptible to such pressures. In addition, two of the obtained quadratic
      effects of social influence lent support to the application of social impact
      theory to drug use. Overall, our findings suggest that interactive and nonlinear
      approaches to social influences on drug use provide a unique and viable
      theoretical perspective from which to construe this problem health behavior.

PMID- 1401849
TI  - Patterns of social affiliation as predictors of depressive symptoms among urban
      blacks.
AB  - This paper focuses on patterns of social affiliation viewed historically as
      sociocultural adaptations to stresses associated with minority group status. Data
      are from a community-based sample of 927 Black adults residing in a large
      metropolitan area. Specifically, this analysis assesses the extent to which
      patterns of social affiliation such as close family ties, religious involvement,
      and participation in voluntary associations diminish the detrimental impact of
      chronic economic strain on the level of depressive symptoms. The findings provide
      no support for a sociocultural adaptation explanation. Moreover, the results show
      an unexpected relationship among religious involvement, chronic economic strain,
      and depressive symptoms. At the most intense levels of religious involvement, a
      significantly higher level of depressive symptomatology was evident among those
      experiencing chronic economic strain. In contrast, those with less religious
      involvement had fewer depressive symptoms when experiencing chronic economic
      strain. Implications of findings are discussed relative to social changes
      affecting patterns of affiliation and sociocultural adaptation in Black
      communities.

PMID- 1401850
TI  - Network range and health.
AB  - The inclusion of network concepts in the stress-distress model of health
      represents a major theoretical advance. Most researchers use the dyadic approach
      of social network analysis to construct network measures of social support.
      Working from the argument that network structure and social support are
      conceptually and empirically distinct, we extend the stress-distress model to
      include measures of network structure (network range) as predictors of exposure
      to stress, access to social support, and distress. We find that the density,
      diversity, and size dimensions of network range affect exposure to stress, access
      to social support, and distress differentially and that, in each case, their
      effects are gender-specific.

PMID- 1401851
TI  - Popular epidemiology and toxic waste contamination: lay and professional ways of
      knowing.
AB  - Building on a detailed study of the Woburn, Massachusetts, childhood leukemia
      cluster, this paper examines lay and professional ways of knowing about
      environmental health risks. Of particular interest are differences between lay
      and professional groups' definitions of data quality, methods of analysis,
      traditionally accepted levels of measurement and statistical significance, and
      relations between scientific method and public policy. This paper conceptualizes
      the hazard-detection and solution-seeking activities of Love Canal, Woburn, and
      other communities as popular epidemiology: the process by which lay persons
      gather data and direct and marshal the knowledge and resources of experts in
      order to understand the epidemiology of disease, treat existing and prevent
      future disease, and remove the responsible environmental contaminants. Based on
      different needs, goals, and methods, laypeople and professionals have conflicting
      perspectives on how to investigate and interpret environmental health data.

PMID- 1401852
TI  - Evaluation of neck discomfort, neck tenderness, and neurologic deficits as
      indicators for radiography in blunt trauma victims.
AB  - Seventeen of 480 adult blunt trauma victims who sustained cervical spine injuries
      (CSI) were studied prospectively. In reliable patients, complaints of neck
      discomfort and tenderness demonstrated sensitivities of 86% and 79%,
      respectively, for CSI. A positive physical examination, defined as neurologic
      deficits, or cervical region discomfort or tenderness was noted in 13 of 14
      reliable individuals sustaining CSI (sensitivity 93%, specificity 16%, positive
      predictive value 3.3%, negative predictive value 98.7%). Lack of absolute
      sensitivity of these studied clinical parameters, either singly or in concert,
      for CSI suggests that eliminating cervical spine radiography on the basis of the
      absence of neck discomfort, tenderness, or neurological deficits in reliable
      blunt trauma victims could result in missed CSI. An enormous prospective data
      base will be required to definitively address the sensitivity of all clinical
      parameters currently employed to determine the need for cervical spine
      radiography in reliable blunt trauma victims.

PMID- 1401853
TI  - Protracted metabolic acidosis: the impact of acute ethanol in hemorrhagic shock.
AB  - The effects of acute ethanol administration on acid-base balance and hemodynamic
      parameters were studied in a canine model. Ten mongrel dogs, anesthetized and
      maintained on a volume ventilator, underwent splenic artery ligation 30 minutes
      prior to study. Group A (N = 5) served as controls. Thirty minutes after drug
      administration, the animals underwent a 20-cc/kg hemorrhage over 15 minutes.
      Thirty minutes postphlebotomy, resuscitation was performed with the same volume
      of homologous blood. Acid-base and hemodynamic parameters were monitored over 3.5
      hours. Ethanol levels peaked 60 minutes following administration at 207 +/- 13
      mg%. During the entire study, no differences were observed in heart rate,
      pulmonary capillary wedge pressure, systemic vascular resistance index, pO2, or
      pCO2, between the two groups. Following hemorrhage, statistically significant
      decreases in pH, mean arterial pressure (MAP), cardiac index (CI), and left
      ventricular stroke work index (LVSWI) developed in group A compared to controls.
      Maximal disparity developed in pH (7.21 +/- 0.05 to 7.33 +/- 0.02, P < 0.01), MAP
      (67 +/- 11 v 110 +/- 9 torr, P < 0.01), CI (1.69 +/- 0.24 compared to 2.72 +/-
      0.19 L/min/M2, and LVSWI (18.7 +/- 1.2 compared to 44.9 +/- 4.8 gr-meter/M2/beat,
      P < 0.01) at 60, 45, 30, and 75 minutes postphlebotomy. In this study, ethanol
      directly or indirectly caused an increased metabolic acidosis and myocardial
      depression in the post-hemorrhage period.

PMID- 1401854
TI  - Objective determination of the optimal red blood cell count in diagnostic
      peritoneal lavage done for abdominal stab wounds.
AB  - The purpose of this study was to determine objectively the optimal value or
      positivity criterion for red blood cell counts in diagnostic peritoneal lavage in
      stab wounds to the anterior abdomen. Our study group consisted of 91 consecutive
      adults with abdominal stab wounds who underwent peritoneal lavage. We excluded
      those patients who met criteria for immediate laparotomy and those with negative
      stab wound exploration. We divided the patients into two groups based on outcome.
      Group 1 consisted of those who had undergone laparotomy and had findings that
      required surgical intervention. Group 2 patients had either undergone laparotomy
      but had no injury requiring surgical intervention or had no surgery and a benign
      hospital course and follow-up. Receiver operator characteristic analysis was done
      on the diagnostic peritoneal lavage RBC counts for both groups. The overlap
      between the groups was minimal, with 75% of patients in Group 1 having > 120,000
      RBC/mm3 and 75% of patients in Group 2 having < 486 RBC/mm3 in the lavage
      effluent. Using the observed probability of 23.1% of patients with abdominal stab
      wounds requiring surgery, a RBC count of 50,000/mm3 discriminated best those
      patients who required surgery from those who did not.

PMID- 1401855
TI  - Bilateral Achilles tendon rupture: an unusual occurrence.
AB  - Bilateral Achilles tendon rupture is an unusual injury. This rare entity usually
      occurs in patients on chronic steroid therapy or with underlying disease.
      Bilateral Achilles tendon rupture is extremely rare in a previously healthy
      individual. A case involving traumatic Achilles tendon rupture as a result of a
      sky diving accident is reported. Evaluation of patients with suspected Achilles
      tendon rupture is briefly reviewed.

PMID- 1401857
TI  - Hamate-metacarpal fracture dislocation.
AB  - A patient is described who punched a brick wall with his clenched fist and
      sustained a fracture of the body of the hamate with dislocation of the ring and
      little finger metacarpals. He was treated successfully with surgery. This is a
      rare injury that is frequently missed on the initial presentation and should be
      considered in the differential diagnosis of posttraumatic ulnar-sided hand pain.

PMID- 1401856
TI  - An adolescent male with an arteriovenous malformation presenting with
      reproducible seizures.
AB  - The patient who presents with new onset seizure is a difficult but common problem
      in emergency medicine. It is more difficult to make a specific etiologic
      diagnosis when the seizure patient is without fever, focal neurological deficit,
      prior medical history, electrolyte or acid-base imbalance. Such a patient with
      new onset seizures presented to our emergency department. The seizures were
      induced by a specific right arm position. The patient's initial evaluation
      included a normal physical examination, screening chemistries, and an unenhanced
      computed tomography (CT scan) of the head. Subsequent contrast-enhanced head CT
      scan and eventual magnetic resonance imaging (MRI) of the brain revealed a large
      arteriovenous malformation (AVM). The differential diagnosis of seizures is long
      and involved, but a majority of these diagnoses can be ruled in or out by simple
      and inexpensive screening examinations. Occasionally, more involved studies are
      indicated than the routine electroencephalogram (EEG) and CT scan. CT scan with
      contrast, angiography, and magnetic resonance imaging (MRI) may be required to
      elucidate the cause of the seizure. Of these, angiography and MRI are the most
      sensitive for AVM, but contrast CT scan is the most readily available with
      acceptable sensitivity and is therefore potentially more beneficial.

PMID- 1401858
TI  - Glass ingestion from fracture of a laryngoscope bulb.
AB  - A 22-month-old child had a generalized tonic-clonic seizure during attempted
      orotracheal intubation and broke the laryngoscope bulb with his teeth. The glass
      was swallowed but passed uneventfully through the gastrointestinal tract. The
      possibility of this unusual complication should be considered when patients at
      risk for seizures are intubated by the orotracheal route.

PMID- 1401859
TI  - Pediatric pancreatic pseudocyst: a case report and review of the literature.
AB  - The differential diagnosis of abdominal pain and mass in children is complicated.
      An uncommon, but potentially life-threatening cause is pancreatic pseudocyst. The
      case of a 3-year-old male with a pancreatic pseudocyst is presented. All
      previously reported cases are reviewed.

PMID- 1401860
TI  - Necrotizing myositis and toxic strep syndrome in a pediatric patient.
AB  - Group A beta hemolytic streptococcus (GABHS) is a common pathogen in infections
      of skin, soft tissue structures, and muscle. Most infections, when recognized and
      treated appropriately, result in a benign course. The development of more
      virulent forms of this organism have resulted in severe life-threatening
      infections. The following case of an immunocompetent host with necrotizing
      myositis and septic shock emphasizes the potential morbidity of GABHS infection.
      The spectrum of soft tissue and muscle infections is reviewed. The
      pathophysiology and emergency management of septic shock from GABHS is discussed.

PMID- 1401861
TI  - Malposition of pediatric gastric lavage tubes demonstrated radiographically.
AB  - Gastric lavage may be indicated in the initial treatment of toxic substance
      ingestion. We retrospectively surveyed the charts of 36 pediatric patients who
      underwent gastric lavage to evaluate the clinical and radiographic evidence
      indicating proper tube placement. Only 14 patients had a radiograph prior to
      lavage, and 50% of these documented malposition. The most common was excess tube
      insertion, stretching the stomach inferiorly towards the pelvis. The
      traditionally acceptable clinical test by auscultation of insufflated air was
      favorable in 100% of patients, thus failing to detect all of the malpositionings
      documented radiographically. We suggest that initial insertion of tube length be
      based on the patient's height or length using an adaptation of Strobel's
      previously published formula for esophageal pH probe placement: Tube Insertion
      Depth (TID), orogastric = 9.7 cm + (0.226 x length of patient in cm) and TID,
      nasogastric = 8 cm + (0.252 x length of patient in cm). These formulae have been
      displayed in graphic form for easy use. Diagnostic imaging remains the only
      certain means to document tube placement. Prospective studies to validate the
      formulae in clinical use are ongoing.

PMID- 1401862
TI  - Toxicity--seizures in an infant caused by (or related to) oral viscous lidocaine
      use.
AB  - A 5-month-old infant with seizures secondary to oral viscous lidocaine toxicity
      is described. Despite prior reports of this complication in the literature, many
      practitioners are unaware of the potential adverse effects of topical lidocaine
      usage in the pediatric patient. Complications of topical lidocaine use and
      recommendations regarding its use in the pediatric patient are discussed.

PMID- 1401863
TI  - The diagnosis of acute myocardial infarction in the emergency department; Part 2.
AB  - At present, routine use of cardiac enzymes in the emergency department (ED)
      cannot be justified, except possibly as a final screen prior to discharge.
      Computer-derived predictive instruments do not surpass the physician's diagnostic
      sensitivity for acute myocardial infarction (AMI), but do demonstrate
      significantly higher specificity. Limited data exist on the utility of
      echocardiography and thallium scanning in the ED. Methods of triaging patients on
      the basis of prognosis are well supported in the literature. The physician's high
      diagnostic sensitivity is maintained at the cost of significant numbers of
      admissions who subsequently rule out for AMI. No single clinical variable or
      combination of clinical variables can reliably confirm or exclude AMI in the ED.
      Ultimately, the physician's clinical assessment must remain the final determinant
      of the necessity for admission. However, judicious use of prediction rules and
      prognostic indicators should improve resource utilization.

PMID- 1401864
TI  - Biomechanical performance of laser-drilled and channel taper point needles.
AB  - The purpose of this study is to evaluate the biomechanical performance of laser
      drilled and channel needle swages. The laser-drilled swages have a more uniform
      circumference that encounters lower drag forces than the channel needle swages.
      In addition, the length of the laser-drilled hole is shorter than that of the
      channel needles, allowing the physician to grasp the laser-drilled needle close
      (3 mm) to the needle end without deformation. These benefits of laser-drilled
      swages indicate that they should replace all channel needles.

PMID- 1401865
TI  - Adult and pediatric pharyngitis: a review.
AB  - Acute pharyngitis is frequently encountered in the ambulatory care setting.
      Although usually of viral etiology, streptococcal disease is the focus of
      diagnostic efforts, in light of significant suppurative and nonsuppurative
      sequelae. The traditional symptoms of fever, adenopathy, and pharyngeal exudate
      are suggestive, but not diagnostic of streptococcal pharyngitis. Thus, the
      importance of diagnostic testing, including Group A beta hemolytic strep antigen
      screen and culture, is emphasized. Recent innovations in therapy include
      modification of antibiotic dosing regimens and use of cephalosporins to improve
      patient compliance.

PMID- 1401866
TI  - Universities, business, and the state government: partners in progress.

PMID- 1401867
TI  - A need to revise the Cyanide Antidote Package instructions.

PMID- 1401868
TI  - Preventing transmission of infection during mouth-to-mouth resuscitation.

PMID- 1401869
TI  - Use of standardized patients in a freshman emergency medicine course.
AB  - The curriculum of our freshman emergency medicine course now includes group
      interviews with standardized patients to introduce communication skills more
      effectively to students. Our goals for the standardized patient encounters are 1)
      to start the interview learning process in a nonthreatening environment, 2) to
      begin to use rudimentary techniques to obtain a history of present illness, 3) to
      gain insight into a patient's perception of a medical interview, and 4) to learn
      to project empathy and compassion when talking with patients. The standardized
      patients technique is one method emergency medicine educators can use to maximize
      effectiveness in undergraduate medical education.

PMID- 1401870
TI  - Objectives to direct the training of emergency medicine residents on off-service
      rotations: research.
AB  - This is the 16th in a series of objectives to direct resident training in
      Emergency Medicine. Research is recognized as an important component of physician
      training, yet it is often neglected in medical school and residency curricula. We
      offer here an objective-based program for resident physicians' exposure to
      research design and methodology.

PMID- 1401871
TI  - An unanticipated increase in patient visits to a pediatric emergency department.
AB  - This study was conducted to explain a more than threefold increase in anticipated
      patient visits associated with the opening of a separate pediatric emergency
      department (PED) 2 miles from the nearest general emergency department.
      Population demographics and data pertaining to visits to other emergency
      departments were obtained. Parents visiting the new PED were surveyed using a
      standardized questionnaire. Over the study period (1984-1989), the city
      population increased by 7%; school population increased by 17%, with no increase
      in birth rate. Total patient visits to the other city hospitals increased by less
      than 10%, while the number of visits to the PED increased 250% over anticipated
      visits. Of children visiting the PED, 48% were less than 5 years old, 30% had
      lived at their current address less than 2 years, and 80% came from the
      geographic area close to the PED. Parental decision to bring the child to the PED
      was as follows: a service perceived to be "for kids" (47%), previous visit (42%),
      closest facility (33%), better service (20%), referred (12%), and pediatrician
      availability (10%). The PED is staffed by licensed pediatricians, whereas the
      general emergency departments are staffed by emergency physicians. We conclude
      that the increase in visits cannot be accounted for by increases in regional
      population base only. Anticipated patient volume to a new health care facility
      should not be based on population demographics only, but on other factors such as
      user perception of facility. Patient or parent preference should also be
      considered.

PMID- 1401872
TI  - Sudden death in the ED: educating residents to compassionately inform families.
AB  - We describe a program used in our emergency medicine residency to help teach
      residents new skills in interacting with survivors following a patient's sudden
      death in the emergency department. This teaching module requires about two and a
      half hours to complete. It includes a brief presentation of new skills,
      videotapes of family notification, resident role play experiences, and a summary.
      Trained volunteers are used as simulated survivors in the role plays. Although
      labor intensive and time consuming, the program offers educational advantages.
      The residents have an opportunity to practice their communication skills in a
      protected setting. In addition, they receive immediate and specific feedback from
      the faculty facilitator, fellow residents, and, most importantly, the simulated
      survivor. Following the role play sessions, residents feel they are more skillful
      in meeting survivors' needs.

PMID- 1401873
TI  - Another drug-related death.

PMID- 1401874
TI  - Blastoderm degeneration, an early embryonic failure in dwarf Single Comb White
      Leghorn chickens.
AB  - Blastoderm degeneration is an early embryonic lethal condition observed in
      selected paired matings within a line of dwarf Single Comb White Leghorn chickens
      that results in a 25% reduction of the hatch of fertilized eggs. The disorder is
      macroscopically evident at 32 h of incubation by the presence of a small
      localized indentation on the outer periphery of the expanding blastoderm. The
      affected blastoderms undergo a series of rapid macroscopic degenerative changes
      that conclude at about 120 h characterized by the presence of dispersed
      blastoderm fragments on the surface of the egg's yolk. Microscopically, this
      embryonic failure appears to manifest itself between Hamburger-Hamilton stages 8
      and 9 of development and is characterized by a series of retarded developmental
      processes: closure of the anterior neuropore, brain vesicle differentiation,
      somite formation, and cardiac development. The disorder is inherited as an
      autosomal recessive trait. Attempts to identify factors that influence the
      disorder have thus far been unsuccessful. The symbol bld is proposed for this
      recessive gene.

PMID- 1401875
TI  - Chromosome conservation in the Bovidae.
AB  - The chromosomes of 12 bovid species were harvested from fibroblast cultures after
      incorporation of bromodeoxyuridine into early replicating DNA. Q-band karyotypes
      were constructed, and, when possible, autosomal arms were numbered according to
      the cattle standard karyotype. Diploid chromosome number ranged from 30 to 60,
      yet, based on band similarity, chromosome-arm homologies were extensive.
      Employing the cattle karyotype as the standard, autosomal-arm differences
      indicative of possible syntenic disruption were noted for only chromosomes 3, 9,
      and 14. While chromosome-arm homologies were extensive, shared homologous biarmed
      chromosomes were rare. The commonness of monobrachially homologous biarmed
      chromosomes among some bovids (e.g., Antilopinae) suggested that reproductive
      isolation and speciation in some instances might have resulted from centric
      fusion events.

PMID- 1401876
TI  - Zaprionus tuberculatus: chromosome map and gene mapping by DNA in situ
      hybridization.
AB  - The genus Drosophila has long been used as a model of karyotype evolution,
      demonstrating change by paracentric inversion and occasional centric fusion of an
      ancestral karyotype of five rod-shaped and one "dot" chromosome. This study
      shows, by mapping D. melanogaster probes hybridized to polytene chromosomes of
      Zaprionus tuberculatus, that this ancestral pattern extends beyond the genus
      Drosophila. A formal polytene chromosome map of Z. tuberculatus is presented.

PMID- 1401877
TI  - Synaptonemal complexes of Xenopus laevis.
AB  - Synaptonemal complexes (SCs) have been analyzed in spread Xenopus spermatocytes
      and oocytes. They showed all the usual features of animal SCs in addition to a
      high incidence of centromere mismatching. A centriole pair is visible throughout
      zygotene and pachytene. At zygotene the ends of SCs are markedly thickened and
      are clustered at the nuclear periphery.

PMID- 1401878
TI  - Rostral cerebellar malformation, (rcm): a new recessive mutation on chromosome 3
      of the mouse.
AB  - A new recessive mutation in the mouse that causes a disorderly arrangement of
      Purkinje and granule cells in the rostral portion of the cerebellum is described.
      The mutation, called rostral cerebellar malformation, rcm, has been located on
      chromosome (Chr) 3 between the alcohol dehydrogenase-3 (Adh-3) complex and
      varitint waddler-J (VaJ).

PMID- 1401879
TI  - Use of DNA fingerprinting to determine parentage in muskrats (Ondatra
      zibethicus).
AB  - The detection of high levels of genetic variability by DNA fingerprinting probes
      has allowed researchers to accurately assess relatedness. Multiple-mating
      strategies are characteristic of the mating systems of small mammals. As such,
      techniques that provide an accurate indication of how individuals are related
      genetically is of great importance to assess the mating system of a species. In
      this study, we applied the DNA fingerprinting technique to captive and wild
      muskrats (Ondatra zibethicus) to determine its usefulness for parentage analysis
      in wild populations. We found that DNA digested with the restriction enzyme Hae
      III and probed with Jeffrey's minisatellite 33. 15 identified a large amount of
      polymorphism in both groups of muskrats. The DNA fingerprinting technique
      correctly assessed parentage within the captive group. In the wild population,
      paternity was assigned between two adult males based on diagnostic fragments and
      similarity of banding patterns. The likelihood that paternity could be
      misassigned to a full sibling was high in this free-ranging population. However,
      because natal dispersal in muskrats is male biased, it is unlikely that two
      brothers would associate with the same female.

PMID- 1401880
TI  - Comparative F statistics analysis of the genetic structure of ten Spanish dog
      breeds.
AB  - The genetic structure and relationships among 10 Spanish dog breeds have been
      studied by using F statistics. Data came from 21 structural genic loci that
      codify for blood-soluble proteins and enzymes detected by electrophoresis. Of the
      21 loci, 11 were found to be polymorphic. The study was done at three levels of
      hierarchical differentiation: ancestral trunks, breeds, and subpopulations. The
      deficit of heterozygotes was estimated at the subpopulation, breed, and ancestral
      trunk levels, with values of 4.0%, 6.5%, and 11.2%, respectively. In the whole
      population, the deficit of heterozygotes was about 17%. The proportion of genetic
      variability attributable to differences between subpopulations, breeds, and
      ancestral trunks was estimated to be 14.2%, 9.9%, and 6.9%, respectively. The
      dendrogram, obtained by using values of genic differentiation (FST) as a measure
      of the genetic distance among populations, is topologically identical to the one
      obtained using Nei's index of distance, which indicates a high correlation (r =
      .99) between both distances. These racial groupings, however, differ from the
      grouping obtained from historical, archeological, and morphological data.

PMID- 1401881
TI  - Use of cellular oncogene probes to identify Morone hybrids.
AB  - We tested the ability of cellular oncogene (c-onc) probes to identify F1 hybrids
      and the lineage of known backcrosses within the fish genus Morone. Total DNA was
      isolated from five to 14 individuals per North American Morone species (striped
      bass, white bass, white perch, and yellow bass). The DNA was digested with two
      restriction enzymes, Eco RI and Hin dIII, Southern blotted, and hybridized to six
      different c-onc probes including v-abl, v-erb B, c-myc, c-H-ras, c-K-ras, and v
      src. We found fixed genotypic differences among the four species for all six
      probes in single restriction enzyme digests. The heritability of these nuclear
      DNA genotypes was evaluated in hatchery-produced F1 Morone hybrids (striped bass
      x white bass and striped bass x white perch) tested with the six informative
      single probe/restriction enzyme combinations. All F1 individuals exhibited
      heterozygosity in all diagnostic nuclear DNA fragments, confirming the Mendelian
      inheritance of these genotypes in these fish. Furthermore, analysis of these
      nuclear DNA genotypes in hatchery-produced backcrosses of F1 hybrids striped bass
      x (white bass x striped bass) detected both recombinant and parental genotypes at
      all six polymorphic c-onc sequences. The lineage of suspected Morone hybrids of
      unknown descent collected from Lewis Smith Lake, Alabama, and from the Occoquan
      River, Virginia, was determined using the c-onc probes. Our results suggest that
      c-onc probes are suitable markers to unequivocally identify F1 hybrids and
      backcrosses and to quantify introgression in natural populations of fishes. The
      addition of RFLP analysis of mtDNA provided a complete ancestral history of
      individual fish.

PMID- 1401882
TI  - IU dean examines primary care issue.

PMID- 1401883
TI  - Recruiting doctors: big job for small towns.

PMID- 1401884
TI  - Rural physicians have chance to make a difference.

PMID- 1401886
TI  - New faces in statehouse may change ISMA strategy.

PMID- 1401885
TI  - Digest of health and medical laws. 1992 Indiana General Assembly.

PMID- 1401887
TI  - Rabies in Indiana: it's still a threat.

PMID- 1401888
TI  - Working vacations in the Third World for physicians and dentists.

PMID- 1401889
TI  - PCP presenting as cavitary pneumonia: a case report.
AB  - As Pneumocystis carinii pneumonia cases increase, physicians must consider the
      various atypical radiographic presentations of the disease. The following case
      report illustrates one atypical presentation and the dramatic response to
      treatment.

PMID- 1401890
TI  - A gathering of friends in memory of Elizabeth Harriet Thomson (1907-1991) held in
      the Historical Library, Yale University School of Medicine, Saturday, 25 January
      1992.

PMID- 1401891
TI  - From guinea pigs to man: the development of Haffkine's anticholera vaccine.

PMID- 1401892
TI  - Biblical accounts of resuscitation.

PMID- 1401893
TI  - The origins of neurochemistry: the chemical study of the brain in France at the
      end of the eighteenth century.

PMID- 1401894
TI  - Protein kinase C isoenzymes display differential affinity for phorbol esters.
      Analysis of phorbol ester receptors in B cell differentiation.
AB  - Protein kinase C (PKC) comprises a family of distinct isoenzymes that are
      involved in signal transduction pathways linking the cell to triggers perceived
      via membrane receptors. These isoenzymes differ in their tissue distribution,
      activation requirements, and substrate specificity. One common denominator among
      different PKC subspecies is their activation by phorbol esters. We have developed
      a sensitive method permitting the measurement of phorbol ester binding sites,
      their quantitation, as well as their dissociation kinetics, by performing
      cytofluorometric analyses on intact cells or on isolated PKC associated to
      phosphatidylserine vesicles incubated in the presence of fluorochrome-labeled
      phorbol ester. Both PKC isozymes beta I/beta II and alpha from brain and spleen
      after incorporation into phosphatidylserine vesicles, display affinities with
      apparent Kd of 120 and 50 nM, respectively; although PKC gamma from brain
      exhibits a Kd of 210 nM. In addition to these receptors, on PKC isozymes from
      spleen, an intermediate affinity phorbol ester receptor (Kd of 3 nM) and an
      additional high affinity phorbol ester binding site with a Kd of 0.1 to 0.5 nM
      were also detected. This latter receptor comigrates with high m.w. PKC isoforms.
      In different cell lines, the phorbol ester binding patterns, as well as the
      expression of individual PKC isoenzymes, could be positively correlated.

PMID- 1401895
TI  - Ganglioside-induced CD4 endocytosis occurs independent of serine phosphorylation
      and is accompanied by dissociation of P56lck.
AB  - Gangliosides induce a selective and complete modulation of CD4 from the surface
      of T cells. CD4 down-modulation occurs by CD4 endocytosis. This process is
      independent of serine phosphorylation of the cytoplasmic tail of CD4 and does not
      require the association between the tyrosine protein kinase p56lck and the
      cytoplasmic tail of CD4. Ganglioside-induced CD4 endocytosis is accompanied by
      the loss of p56lck activity associated with CD4. Sequential immunoprecipitation
      analysis using an anti-CD4 antibody and an anti-p56lck antiserum showed that this
      is caused by the dissociation of the enzyme from the cytoplasmic tail of CD4. The
      kinetics of p56lck dissociation after ganglioside treatment is identical to that
      of CD4 endocytosis, suggesting that p56lck is displaced in the process of
      endosome formation. The results indicate that CD4 endocytosis alone can cause the
      dissociation of the p56lck complex without the requirement for CD4
      phosphorylation.

PMID- 1401896
TI  - Ultrastructures and interactions of complement factors H and I.
AB  - The human complement regulatory protein, factor H, was examined by high
      resolution transmission electron microscopy. Results of electron microscopy
      confirm hydrodynamic analysis and indicate that factor H is a monomer of M(r)
      approximately 155,000. Factor H is an extended flexible molecule with a contour
      length of 495 A and a cross-sectional diameter of 34 A. Most images of factor H
      indicate that its polypeptide chain typically folds back on itself with the
      result that the average length of a factor H molecule is about half its contour
      length. Only one end of factor H associates with C3b. When bound to C3b, factor H
      still shows considerable conformational flexibility. Factor I is a bilobal
      protein of 130 A in length, and its two globular parts have maximal diameters of
      54 and 49 A. The results establish that factor I is a two domain protein where
      the smaller subunit is a protease and the larger one is involved with binding
      C3b. Factor I binds C3b with a one-to-one stoichiometry in an ionic strength
      dependent fashion. In the absence of sodium chloride an affinity constant of 5.7
      x 10(5) M-1 was determined for factor I interaction with C3b. Whereas the
      Scatchard plot of factor I binding to C3b in the absence of factor H is linear,
      in the presence of factor H a curvilinear graph is obtained. The strong binding
      sites on C3b for factor I have an affinity at least 15-fold higher in the
      presence of factor H than in its absence. The results of both electron microscopy
      and binding studies were combined to compose a scheme envisioning how factors H
      and I cooperate for the processing of C3b.

PMID- 1401897
TI  - Structural diversity in the extracellular faces of peptidergic G-protein-coupled
      receptors. Molecular cloning of the mouse C5a anaphylatoxin receptor.
AB  - The mouse C5a receptor gene was isolated using the human C5a receptor cDNA probe
      recently described (Gerard, N. P., and C. Gerard. 1991. Nature 349:614). By
      analogy with the human gene, the mouse homolog contains two exons with the 5'
      untranslated region and initiating methionine codon present in exon 1 and the
      remainder of the molecule in exon 2. Generation of an expressible cDNA for the
      mouse C5a receptor was accomplished using the polymerase chain reaction and a
      sense oligodeoxynucleotide primer which included an initiation codon just 5' to
      the sequence encoding the N-linked glycosylation site. When transfected into
      human 293 kidney epithelial cells the cloned cDNA directs expression of a binding
      site for human C5a anaphylatoxin with a binding constant of 2.5 +/- 0.3 nM; the
      human C5a receptor expressed under identical conditions has a Kd of 1.7 +/- 0.2
      nM. Overall, the deduced amino acid sequences of the receptors are 65% identical
      given the analogous gene structures. Alignment of the sequences as seven
      transmembrane segment receptors reveals that the greatest structural diversity
      (approximately 70%) exists in the putative extracellular domains. In contrast,
      species differences among other members of this family of seven membrane-spanning
      receptors is generally only 10 to 20%, even for receptors whose ligands are
      relatively small and not expected to interact with sites on the extracellular
      surfaces. A high degree of structural identify is observed for the C5a receptors
      in the transmembrane segments and in all but one of the loops predicted to exist
      in the cytoplasm. Inasmuch as critical structures responsible for high affinity
      binding of the 74 amino acid polypeptide to both C5a receptors involve features
      conserved between species, these data provide the starting point for mutagenesis
      studies to determine the nature of the binding and activation sites for the
      chemotactic receptors. Additionally, these data provide a reagent for immunologic
      and molecular genetic studies on the role of C5a receptors in inflammatory
      models.

PMID- 1401898
TI  - Dissection of the combining site in a humanized anti-Tac antibody.
AB  - The genetically engineered "humanized" anti-Tac antibody (HAT) has been shown to
      bind the p55 chain of the human IL-2R with an affinity close to that of the
      murine anti-Tac. Although the HAT molecule contains all six mouse CDR, it was not
      known which, and to what extent, each of the CDR contributes to Ag binding. These
      questions were addressed by constructing a series of variant HAT antibodies, each
      substituting a single HAT CDR with a heterologous CDR. The association constants
      of the variant HAT antibodies to p55 were determined by competitive binding
      analysis. We find that CDR 1 and 3 of the H chain and CDR 3 of the L chain are
      essential for maintaining binding. The remaining three CDR appear to be involved
      to a lesser degree.

PMID- 1401900
TI  - Structure and function of the murine perforin promoter and upstream region.
      Reciprocal gene activation or silencing in perforin positive and negative cells.
AB  - Gene expression of the cytolytic protein perforin is restricted to and tightly
      regulated in cytolytic lymphocytes. To begin to understand the molecular basis of
      perforin gene transcription, we cloned and analyzed 5.1 kb of the genuine murine
      perforin promoter and upstream region. The murine perforin promoter is located
      approximately 2.1 kb upstream of the translation start codon in the genomic DNA
      due to an intron in the 5' untranslated sequence. Although the sequenced murine
      promoter and upstream region was found to be quite homologous to that of the
      human gene, most of the interspecies conserved sequences lacked obvious consensus
      to known regulatory elements. Functional analysis of this region, however,
      indicated that it contains regulatory elements that may determine the cell-type
      specific expression of this killer protein. After transient transfection into
      several cell lines, the perforin promoter and upstream region was used to drive
      the expression of the chloramphenicol acetyltransferase (CAT) reporter gene. High
      levels of CAT activities, exceeding 110 times the expression of a promoterless
      reporter gene construct, were expressed in CTL. In contrast, in perforin-negative
      cell types the perforin promoter and upstream region mediated barely detectable
      transcription of the CAT gene. Analysis of the immediate proximal perforin
      promoter, -120 to +2, revealed that it was ubiquitously active and that it
      expressed in all cells tested 20- to 50-fold higher CAT activity than the
      promoterless reporter gene construct. The cell-type restricted transcriptional
      activity of the perforin promoter and upstream region, however, was controlled by
      at least four negative and positive cis-acting upstream regions that spread over
      the entire 5 kb of the cloned DNA and acted reciprocally in different cells.
      Thus, in perforin-negative cells, the transcriptional activity of the immediate
      proximal perforin promoter was dominantly suppressed by several upstream negative
      regulatory elements, whereas in perforin-positive cells, the promoter activity
      was enhanced more than fivefold by several upstream regulatory elements.

PMID- 1401899
TI  - Isolation and characterization of cDNA clones for the mouse thymocyte B cell
      antigen (ThB).
AB  - The Thb locus is responsible for the expression of 15-kDa phosphatidyl inositol
      anchored molecules (ThB) on murine thymocytes and B cells. Thb expression as
      detected with mAb is polymorphic on B cells with two alleles, Thbh and Thb1
      responsible for the high and low expression of ThB on B cells. The regulatory
      locus for Thb expression had been mapped with the Ly-6 cluster of genes to Chr
      15. In our study we used expression cloning in COS cells to isolate cDNA clones
      that code for ThB after transfection; the cDNA products react with anti- ThB
      antibodies, but not with Ly-6A.2, -6B.2, -6C.2, or -6D.2 antibodies. One of these
      clones, pThB-A contains insert of 702 bases which was sequenced. The translated
      amino acid sequence has 11 cysteine residues, and together with the absence of
      potential N-linked glycosylation sites is similar to the structure of the Ly-6
      molecules. The nucleotide and amino acid sequences of ThB cDNA were compared to
      those of Ly-6 genes and the Ly-6 related human CD59 and show clear homology.
      Finally using interspecies crosses, the structural Thb gene has been mapped to
      Chr 15; thus both structural and regulatory genes map to a similar site. The
      genetic map location near Ly-6 and the sequence similarity suggest that Thb and
      Ly-6 may have been derived from the same progenitor by gene duplication.

PMID- 1401901
TI  - Structural relationship between the two IgY of the duck, Anas platyrhynchos:
      molecular genetic evidence.
AB  - cDNA clones encoding the H chains of the 7.8S and 5.7S IgY of the White Pekin
      duck have been isolated and sequenced. The H chain of the 7.8S IgY possesses four
      C region domains and thus resembles the H chain of chicken IgY with which it
      shows, in the C region, 54% inferred amino acid sequence identity, and complete
      conservation of the C region cysteine and tryptophan residues. The H chain of the
      5.7S IgY possesses only two C region domains, that are virtually identical to CH1
      and CH2 of the 7.8S IgY H chain. Although Southern blot genomic analysis did not
      resolve whether the two transcripts encoding the H chains of the 7.8S and 5.7S
      IgY are derived from one or two H chain-encoding genes, the CH 1, 2, 3, and 4
      exons are apparently colinear, and no evidence was found for a separate locus in
      which CH1 and 2 exons were present and CH3 and 4 exons were lacking. The VH
      domain-encoding sequences of the cDNA for the two IgY H chains showed high
      similarity in the inferred VH gene (93% nucleotide and 91% inferred amino acid
      identity) and in the inferred JH segment (89% nucleotide and 93% inferred amino
      acid identity) but low similarity in the D region (26% nucleotide and 7% inferred
      amino acid identity). Genomic Southern blot hybridization analysis showed
      multiple VH-hybridizing sequences represented on up to 20 restriction fragments.

PMID- 1401902
TI  - DRB1*0301 molecules recognize a structural motif distinct from the one recognized
      by most DR beta 1 alleles.
AB  - The DR3-restricted peptide, MT 65 kDa 3-13, was used to develop a DR3-specific
      binding assay. The binding activity detected was strictly pH-dependent, in that
      it was optimal in the pH 4 to 5 range, and no activity was detected at neutral
      pH. By means of affinity chromatography purifications and the use of DR3
      transfected fibroblasts, it was shown that no cross-reactivity exists at the
      level of DR52a molecules, thus allowing use of only partially purified DR3/DR52a
      mixtures in high throughput binding assays. The immunologic relevance of the
      assay established was also verified by examining the correlation between DR3
      restriction and binding for a panel of DR-restricted peptides. When the
      structural requirements for peptide DR3 interactions were further examined by
      using panels of analogues of two different epitopes (Myo 132-151 and TT 830-843),
      it was found that DR3 molecules recognized a peptide motif distinct from the one
      recognized by the other major DR beta 1 alleles.

PMID- 1401903
TI  - Identification and characterization of the murine homologue of CD22, a B
      lymphocyte-restricted adhesion molecule.
AB  - The human B lymphocyte-specific Ag, CD22, is a cell adhesion molecule expressed
      on the surface during a narrow window of B cell development, coincident with
      surface IgD. A ligand for CD22 has recently been identified on human T cells as
      the low molecular mass isoform of the leukocyte common Ag, CD45RO. CD22 has been
      reported to function in the regulation of both T and B cell activation in vitro.
      In this study, we report the isolation and expression of a molecular cDNA clone
      encoding the murine homologue of CD22, mCD22. Within their predicted protein
      sequences, murine and human sequences overall have 62% identity, which includes
      18 of 20 extracellular cysteines and six of six cytoplasmic tyrosines. BHK cells
      transfected with mCD22 cDNA specifically adhere to resting and activated T
      lymphocytes and in addition bound activated, but not resting, B cells. Five Th
      clones were analyzed for their ability to adhere to mCD22; two Th0 clones and one
      Th1 clone bound CD22+ BHK transfectants, but not all T cell clones bound CD22+
      cells: another Th1 clone and a Th2 clone did not. mCD22+ BHK transfectants were
      also specifically bound by the B cell-specific mAb, NIM-R6, demonstrating that
      this mAb is specific for murine CD22. Human cell lines expressing the counter
      receptors for human CD22 were also examined for adhesion to the murine CD22
      homologue; the epitope responsible for B cell adhesion to CD22 is conserved,
      whereas the T cell epitope binding to CD22 is not. The cDNA and mAb to murine
      CD22 will be useful for defining the in vivo function of CD22.

PMID- 1401905
TI  - IFN-gamma/lipopolysaccharide activation of macrophages is associated with protein
      kinase C-dependent down-modulation of the colony-stimulating factor-1 receptor.
AB  - IFN gamma/LPS treatment increases macrophage tumoricidal and microbicidal
      activity and inhibits CSF-1-induced macrophage proliferation. The mechanism
      underlying the latter effect was investigated in the CSF-1-dependent mouse
      macrophage cell line, BAC-1.2F5. IFN-gamma and LPS together dramatically reduced
      the total number of CSF-1 receptors (CSF-1R) via selective degradation of the
      cell surface form. Processing and transport of intracellular CSF-1R to the cell
      surface were unaffected. IFN-gamma alone had no effect but significantly enhanced
      LPS-induced CSF-1R down-regulation. The reduction in CSF-1R number was protein
      kinase C-dependent and involved changes in serine phosphorylation of the receptor
      at different sites. CSF-1R down-modulation by this mechanism may be important in
      switching off the energy-consuming processes of CSF-1R-mediated proliferation and
      chemotaxis in activated macrophages.

PMID- 1401904
TI  - Isolation, characterization, and expression of mouse ICAM-2 complementary and
      genomic DNA.
AB  - Intercellular adhesion molecule-2 (ICAM-2), a cell surface glycoprotein, is a
      second counter-receptor for lymphocyte function-associated Ag-1 (LFA-1). We
      report here the isolation and characterization of the cDNA and the gene that
      encode murine ICAM-2 (Accession numbers X65493 and X65490, respectively). The
      deduced sequence of the cDNA has 60% amino acid identity with its human
      counterpart and has the same expression pattern in cells and tissues.
      Furthermore, COS cells transfected with mouse ICAM-2 complementary and genomic
      DNA bind to purified human LFA-1, demonstrating the conservation of the function
      of ICAM-2 as a ligand for LFA-1 and conservation across species of sequences that
      are critical for binding to human LFA-1. COS cells transfected with the ICAM-2
      cDNA do not react with mAb PA3, previously suggested to define ICAM-2 in the
      mouse. The mouse ICAM-2 gene was isolated and its structural organization
      determined. The gene is present in a single copy in the mouse genome and contains
      four exons spanning about 5.0 kb of DNA. The exon/intron architecture correlates
      to the structural domains of the protein and resembles that of other Ig
      superfamily members. The gene for ICAM-2, which is constitutively expressed in
      endothelial cells, has several conserved sequence motifs in its promoter region,
      including a direct repeat, and lacks transcription factor-binding sites present
      in the ICAM-1 gene, which is inducible in endothelial cells.

PMID- 1401906
TI  - Interference with cyclophosphamide-induced skin allograft tolerance by
      cyclosporin A.
AB  - In a murine strain combination identical in H-2 Ag but disparate in minor
      histocompatibility (H) Ag consisting of C3H/He (C3H; H-2k, Mls-1b) mice as
      recipients and AKR/J (AKR; H-2k, Mls-1a) mice as donors, a permanent skin
      allograft tolerance can be achieved by the cyclophosphamide (CP)-induced
      tolerance system that consists of i.v. injection of donor spleen cells (day -2)
      and i.p. injection of CP 2 days later (day 0). Such permanent take of allografts
      in CP-induced tolerant mice was interfered with by intramuscular injection of
      cyclosporin A (CsA) from day -5 to day -1 and their grafts were rejected by 21
      days after grafting. Mls-1a-reactive CD4+V beta 6+ T cells in the periphery, as
      the indicator to follow the kinetics of donor-reactive T cells, increased on day
      0 and day 3 in the C3H mice treated with AKR spleen cells alone, whereas they
      disappeared rapidly from day 0 to day 3 in CP-induced tolerant mice. When CsA
      capable of interfering with IL-2 production and T cell proliferation was
      administered before CP treatment in CP-induced tolerance system, the number of
      CD4+V beta 6+ T cells in periphery did not increase on day 0 and 3, but increased
      on day 7 in contrast to the decreased number of those in CP-induced tolerant
      mice. On day 7, MLR against donor cells was decreased in CP-induced tolerant
      mice, but maintained in CsA-interfered tolerant mice. These result may indicate
      that the destruction of donor-Ag-stimulated, proliferating T cells by CP is
      interfered with by CsA, probably because CsA inhibits the proliferation of donor
      reactive T cells at the time of CP treatment. Furthermore, these results also
      implicate that the protocol for immunosuppression with CsA and antimetabolites
      has to be designed carefully in clinical transplantation.

PMID- 1401907
TI  - Localization of IFN-gamma receptor in first trimester placenta to trophoblasts
      but lack of stimulation of HLA-DRA, -DRB, or invariant chain mRNA expression by
      IFN-gamma.
AB  - Trophoblasts do not express MHC class II Ag on their cell surface, but it is not
      known at which level the regulation of expression of these IFN-gamma-responsive
      genes occurs. We localized the IFN-gamma R Ag to the trophoblasts of normal human
      first trimester placenta. As previously shown, treatment with IFN-gamma of short
      term cultures of placental explants did not induce expression of HLA-DR Ag in
      trophoblasts. We demonstrated that in situ hybridization with probes for DRA,
      DRB, and MHC class II-associated invariant chain genes gave no detectable signals
      for the presence of the corresponding mRNA in cytotrophoblasts or
      syncytiotrophoblasts of first trimester placenta with or without IFN-gamma.
      Maternal leukocytes in these placental preparations as well as IFN-gamma-treated
      HeLa cell control cultures expressed these mRNA. In addition, Northern analysis
      of RNA isolated from the trophoblast cell line Jar after treatment with IFN-gamma
      showed that induction of transcription did not occur from the HLA-DRA, HLA-DRB,
      or invariant chain genes. Jar cells expressed the IFN-gamma R Ag. These data
      suggest that down-regulation of MHC class II Ag on trophoblasts in the first
      trimester placenta and in a cell line include a lack of productive intracellular
      signaling by the IFN-gamma R and maintenance, in a coordinate manner, of low
      steady state levels of the mRNA encoded by the DRA, DRB, and invariant chain
      genes.

PMID- 1401908
TI  - Identification of IL-8 as a locomotor attractant for activated human lymphocytes
      in mononuclear cell cultures with anti-CD3 or purified protein derivative of
      Mycobacterium tuberculosis.
AB  - On culture of human blood mononuclear cells for 24 to 48 h with anti-CD3 (aCD3)
      or purified protein derivative of Mycobacterium tuberculosis, chemoattractants
      are released into the medium which induce polarization and locomotion of
      activated (G1) lymphocytes but not resting lymphocytes. Here we show that, during
      a period of up to 72 h of culture, IL-8 is released in nanomolar quantities into
      the supernatant and that the lymphocyte chemoattractant activity of these
      supernatants is inhibited by incubation with anti-IL-8. Examination of the
      cultured mononuclear cells by immunofluorescence suggests that many monocytes,
      but almost no lymphocytes in aCD3 cultures contain IL-8 in cytoplasmic
      organelles, yet few monocytes direct from blood stained for IL-8. IL-8 is an
      attractant for only a small proportion (ca 10%) of lymphocytes direct from blood.
      The proportion of responding cells is increased after culture for 24 to 48 h in
      aCD3 or purified protein derivative of Mycobacterium tuberculosis, and these are
      a phenotypically distinct subpopulation consisting of large lymphocytes enriched
      for CD45RO. These cells respond to their own culture supernatants and to IL-8 in
      polarization assays and by invasion of collagen gels into which the attractants
      are incorporated. They also show orientation to a source of IL-8 in a chemotactic
      gradient. These responses are consistent with in vivo observations that the
      lymphocytes which migrate selectively into inflammatory sites are activated. The
      fact that many lymphocytes do not respond to IL-8 may reflect the diversity of
      migratory pathways shown by lymphocytes in vivo, the locomotion of small,
      recirculating, lymphocytes being regulated by other, unknown, locomotor stimuli.

PMID- 1401909
TI  - Recognition of different domains of the Plasmodium falciparum CS protein by the
      sera of naturally infected individuals compared with those of sporozoite
      immunized volunteers.
AB  - The fine specificities of antibodies to the circumsporozoite (CS) protein of
      Plasmodium falciparum, present in the sera of volunteers immunized with
      irradiated P. falciparum sporozoites, were defined and compared to those of sera
      from persons living in a malaria-endemic area in West Africa. The specificity of
      these anti-CS antibodies was determined by ELISA, using recombinant proteins and
      synthetic peptides containing repeat and nonrepeat sequences of this CS protein.
      All 10 serum samples of the five sporozoite-immunized volunteers displayed very
      high antibody titers to the immunodominant repeat (NANP)n of the CS protein.
      However, only three of the serum samples of these vaccinees reacted with a single
      nonrepeat region and only at low titers. In contrast, a high percentage of sera
      from adults living in the malaria-endemic area who had been exposed to
      sporozoites, as well as liver and blood stages of P. falciparum, had high
      antibody levels, not only to the repeats but also to several nonrepeat regions of
      the CS protein. Furthermore, a number of sera from children living in this
      endemic area displayed appreciable levels of antibodies to the nonrepeat regions,
      in the absence of any antirepeat reactivity. Sera of Saimiri monkeys, which had
      undergone multiple blood-induced P. falciparum infections, consistently contained
      high titers of antibodies to several nonrepeat sequences of the CS protein,
      whereas only a few of these sera had low titers of antirepeat antibodies.
      Antibody binding sites, in nonrepeat regions, were mapped using synthetic
      polymers containing multiple copies of selected C-terminal sequences of the P.
      falciparum CS protein. The binding to sporozoites of antibodies to nonrepeat
      regions of the CS protein was determined. The basis for the differences in
      antibody binding sites of sera from persons immunized with irradiated
      sporozoites, compared to those from an endemic area, is discussed.

PMID- 1401910
TI  - Macrophage arginine metabolism and the inhibition or stimulation of cancer.
AB  - The potential of the immune system to inhibit or stimulate tumor growth is a
      vivid example of the "two-edged sword" nature of immune responses. Our results
      provide evidence that this dual capacity can be attributed, in part, to the dual
      pathways of arginine metabolism exhibited by intratumor macrophages.
      Specifically, i.p. tumor rejection in P815-preimmunized mice is accompanied by an
      upshift in intratumor macrophage arginine metabolism to the nitric oxide (NO)
      synthase pathway that yields citrulline and NO. A rapid and marked local increase
      in IFN-gamma (both mRNA and protein) in preimmunized mice during tumor rejection
      suggests that this cytokine plays a role in up-regulating nitric oxide production
      in vivo. Unlike tumor rejection, progressive i.p. P815 tumor growth in naive mice
      is associated with a marked decline in the production of citruline/NO by
      intratumor macrophages. Examination of macrophage arginine metabolism via
      arginase revealed a pattern opposite that of NO synthase. The local production of
      ornithine/urea markedly increases during progressive tumor growth whereas
      arginase activity decreases during tumor rejection. Inasmuch as nitric oxide
      inhibits tumor cell replication whereas ornithine is the precursor of polyamines
      required for cell replication, these results are consistent with the conclusion
      that the pathway macrophages use to metabolize arginine can influence the type of
      host immune responses against cancer and other conditions.

PMID- 1401911
TI  - Expression of the 50-kDa integrin-associated protein on myeloid cells and
      erythrocytes.
AB  - Integrin-associated protein (IAP) is a 50-kDa intrinsic membrane protein that is
      involved in signal transduction during neutrophil activation by a variety of Arg
      Gly-Asp-containing ligands. However, IAP does not itself directly bind these
      ligands, which are instead recognized by the leukocyte response integrin (LRI).
      In fact, IAP is more widely expressed than the LRI and is even on erythrocytes,
      which express no known integrins. This suggests that IAP may have additional
      functions besides signal transduction in association with the LRI. In this work
      we have quantitated IAP expression on several myeloid cells and cell lines, as
      well as erythrocytes, using a mAb which recognizes this protein. These data show
      that there are about 10,000 IgG-binding sites on each erythrocyte and 20 times
      that number on the myeloid cell lines U937 and HL60. Normal PMN and monocytes
      express about 25,000 IgG-binding sites. There are twice as many Fab'-binding
      sites on each cell, suggesting that each IgG binds via both Ag-combining sites.
      Binding data using several mAb to IAP suggest that IAP undergoes a temperature
      dependent conformational change. Unlike some integrin receptors, IAP is not
      stored in a regulated secretory compartment in polymorphonuclear leukocytes
      (PMN). In addition, there is no evidence for internalization or shedding of IAP
      upon PMN activation. These data show that IAP is expressed at significant levels
      on myeloid cells and erythrocytes and that its expression is unaffected by the
      state of PMN activation.

PMID- 1401912
TI  - Spontaneous development of protective anti-T cell receptor autoimmunity targeted
      against a natural EAE-regulatory idiotope located within the 39-59 region of the
      TCR-V beta 8.2 chain.
AB  - The development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats
      is mediated by V beta 8.2+ T cells specific for myelin basic protein. One
      consequence of this biased expression of V beta 8.2 is the spontaneous
      development of regulatory T cells and antibodies against residues 39-59 of the V
      beta 8.2 sequence. Moreover, a synthetic V beta 8.2-39-59 peptide could induce
      protection against and speed recovery from EAE. T cells and antibodies specific
      for V beta 8.2-39-59 could transfer protection from EAE. Recently, we reported
      that the protective T cell epitope is subsumed within the V beta 8-44-54
      sequence. We now report that protection induced by V beta 8-44-54 lasted at least
      102 days and produced "split tolerance," enhancing anti-myelin basic protein
      antibody titers but reducing anti-myelin basic protein T cell frequency. The
      shorter V beta 8-44-54 peptide induced a distinct set of antibodies that did not
      cross-react with the longer V beta 8.2-39-59 peptide, although both specificities
      could stain V beta 8.2+ T cells and were equally protective against EAE. However,
      the V beta 8.2-39-59 peptide, but not the V beta 8-44-54 peptide, would appear to
      represent the natural idiotope: antibodies to V beta 8.2-39-59 that develop
      spontaneously during EAE could be boosted to higher titers only by the V beta 8.2
      39-59, but not by other TCR peptides from the V beta 8.2 sequence, including V
      beta 8-44-54 that contains the functional T cell epitope. These results suggest
      that natural processing of the TCR V beta-chain favors the formation of a peptide
      that resembles the V beta 8.2-39-59 sequence. The B cell epitope present on the V
      beta 8-44-54 sequence was evident only in the absence of residues 39-43 and 55
      59, suggesting that the two peptides possess distinct conformations. However, the
      V beta 8-44-54 B cell epitope is most likely expressed on the V beta 8.2+ T
      cells, either as a low affinity determinant on the intact TCR alpha/beta
      heterodimer or as a cryptic epitope bound in the cleft of surface MHC molecules.

PMID- 1401914
TI  - Regulation of low affinity IgE receptor (CD23) expression on mononuclear
      phagocytes in normal and asthmatic subjects.
AB  - Mononuclear phagocytic cells contain low affinity receptors for IgE (Fc epsilon
      RII or CD23) which induce cellular activation in the presence of specific
      allergen. These studies were performed to quantify the expression by monocytes
      and alveolar macrophages of Fc epsilon RII in asthma and to determine biologic
      response modifiers that regulate Fc epsilon RII. Whereas 2.5 +/- 1.0% of the
      monocytes obtained from normal volunteers were Fc epsilon RII positive, this
      increased to 16.7 +/- 2.4% in asthma (p < 0.001). Stimulation of Fc epsilon RII
      expression on monocytes was shown to be an activity of IL-4 (24.5 +/- 5.9%),
      granulocyte-macrophage-CSF (28.1 +/- 5.2%), IFN-alpha (15.8 +/- 5.3%), IFN-gamma
      (10.4 +/- 3.7%), and macrophage-CSF (7.3 +/- 0.7%) but not of IL-2, IL-6, or TNF
      alpha. Expression of Fc epsilon RII by these cytokines was associated with the
      induction of specific mRNA transcripts. Using Fc epsilon RII subtype specific
      primers in the polymerase chain reaction expansion of cDNA, cytokine-induced
      receptors were shown to be Fc epsilon RIIb. Alveolar macrophages from
      nonasthmatic subjects displayed minimal expression of Fc epsilon RII (3.2 +/-
      1.2%); however, these receptors were present on 69.2 +/- 6.3% of asthmatic
      volunteers (p < 0.001). Induction of Fc epsilon RII appears specific for allergic
      asthma insofar as these receptors are also not expressed in subjects with
      interstitial lung disease (1.3 +/- 1.3%). As assessed by shift in mean
      fluorescence, instillation of allergen in the asthmatic's airway further up
      regulated Fc epsilon RII on alveolar macrophages by 151 +/- 7%. Up-regulation of
      Fc epsilon RII in atopic individuals may therefore reflect allergen-induced
      exposure of mononuclear phagocytes to one or more of these cytokines. These
      studies suggest a mechanism by which an immunologic stimulus that leads to the
      production of these cytokines (e.g., allergen or viral infection) would
      contribute to the development or exacerbation of allergic disease.

PMID- 1401916
TI  - Priming of the respiratory burst of bone marrow-derived macrophages is associated
      with an increase in protein kinase C content.

PMID- 1401915
TI  - Engraftment of human peripheral blood leukocytes into severe combined
      immunodeficient mice results in the long term and dynamic production of human
      xenoreactive antibodies.
AB  - Severe combined immunodeficient (SCID) mice engrafted with human peripheral blood
      leukocytes (hu-PBL-SCID) represent a potentially important small animal model for
      the study of human immune function. Attempts to generate human primary immune
      responses to exogenous Ag in the hu-PBL-SCID have had limited success which
      raises questions about the functional capacity of human lymphocytes in the SCID
      environment. Here, we demonstrate that the spontaneously secreted human Ig in hu
      PBL-SCID includes antibodies with specificity for several different mouse RBC
      (mRBC) proteins. These antibodies apparently reflect the transfer of peripheral B
      cells which are responsible for the production of naturally occurring
      xenoreactive antibodies in the donor. Western blot analysis showed that
      engraftment of anti-mRBC specificities was random among mice receiving PBL from
      the same donor sample. In at least one mouse, this engraftment was polyclonal and
      included human IgM and IgG which recognized at least 12 different mRBC proteins
      ranging in size from 35 to > 200 kDa. Anti-mRBC specificities were found to vary
      with time demonstrating a dynamic expression of the human xenoreactive repertoire
      in hu-PBL-SCID. In contrast to mice engrafted with human PBL, mice engrafted with
      another source of human B cells, i.e., tumor-infiltrating leukocytes, produced
      very little or no human anti-mRBC antibody. Ag-driven proliferation of
      xenoreactive clones may result in a skewing of the engrafted human B cells in hu
      PBL-SCID which could account in part for the limited ability of hu-PBL-SCID to
      respond to exogenous Ag. The long term production of anti-mRBC antibodies and the
      modulation of the expressed xenoreactive repertoire observed in hu-PBL-SCID
      represents an opportunity to study the molecular genetics and cell biology of the
      human humoral immune response to a defined complex Ag.

PMID- 1401913
TI  - Mik-beta 1(Fv)-PE40, a recombinant immunotoxin cytotoxic toward cells bearing the
      beta-chain of the IL-2 receptor.
AB  - Mik-beta 1 is a mAb that binds to the beta subunit of the IL-2R. We have
      constructed a recombinant single chain immunotoxin Mik-beta 1(Fv)-PE40 by
      genetically fusing the H and L V domains of Mik-beta 1 to each other via a
      peptide linker, and then to PE40, a derivative of Pseudomonas exotoxin. Mik-beta
      1(Fv)-PE40 was selectively cytotoxic for cells expressing high levels of IL-2R
      beta (p75) subunit. Mik-beta 1(Fv)-PE40 was cytotoxic to the NK cell line YT-S,
      which expresses p75 but not p55 subunits, with an IC50 of 6 ng/ml. The ATL line
      HUT-102 was less sensitive, with an IC50 of 200 ng/ml. However, the IC50 could be
      lowered to 11 ng/ml when Mik-beta 1(Fv)-PE40 was allowed to bind to HUT-102 cells
      at 4 degrees C for 4 h before overnight incubation at 37 degrees C. An excess of
      Mik-beta 1 but not of anti-Tac, the anti-p55 mAb, prevented the cytotoxicity of
      Mik-beta 1(Fv)-PE40. We constructed a more active version of Mik-beta 1(Fv)-PE40,
      designated Mik-beta 1(Fv)-PE40KDEL, by converting the carboxyl-terminus of the
      toxin from -REDLK to -KDEL. Mik-beta 1(Fv)-PE40KDEL showed an IC50 of 2 ng/ml
      toward YT-S cells and 35 ng/ml toward HUT-102 cells. Binding studies using
      radioiodinated Mik-beta 1 showed that Mik-beta 1(Fv)-PE40 bound to the p75
      receptor subunit with 11% of the affinity of the native Mik-beta 1 antibody. Mik
      beta 1(Fv)-PE40 may be a useful reagent to study cells that express IL-2R, and it
      deserves further study as a possible treatment for cancers in which the malignant
      cells express high numbers of p75 subunit.

PMID- 1401917
TI  - Human pre-B and B cell membrane mu-chains are noncovalently associated with a
      disulfide-linked complex containing a product of the B29 gene.
AB  - B cell activation after Ag binding to membrane Ig (mIg) is mediated by a complex
      series of events that involves proximal activation of a tyrosine kinase and
      phospholipase C. Until recently it was unclear how mIgM and mIgD, with their
      limited cytoplasmic domains (three amino acids on each H chain), were able to
      couple to these secondary signal transducers. Studies of murine B cells conducted
      in several laboratories, including our own, suggest that products of the mb-1
      (IgM-alpha or IgD-alpha) and B29 (Ig-beta, Ig-gamma) genes occur as disulfide
      linked alpha/beta and alpha/gamma heterodimers that are noncovalently associated
      with mIgM and mIgD. Although studies utilizing Daudi and Raji cell lines indicate
      that human mIgM is also associated with a dimer containing the mb-1 gene product,
      the other molecules associated with the human receptor have not been identified.
      In this report we characterize the phosphoproteins that are noncovalently
      associated with mIgM on human tonsillar B cells and human pre-B cell lines. mIgM
      is noncovalently associated with a disulfide-linked heterodimer composed of
      variably glycosylated forms of two core proteins with apparent molecular mass of
      26.5 and 27 kDa. Western blotting analysis reveals that the lower m.w. component
      of each of the mIgM-associated heterodimers and its 27-kDa deglycosylated core
      protein are reactive with antibodies against the murine B29 gene product. Thus, a
      product of the B29 gene is a component of the AgR complex in human and murine B
      cells, occurring as a disulfide linked dimer with product(s) of the mb-1 gene.
      Interestingly, mb-1 and B29 gene products expressed on human cells are much more
      heterogenously N-glycosylated than their murine B cell counterparts.

PMID- 1401919
TI  - C33 antigen recognized by monoclonal antibodies inhibitory to human T cell
      leukemia virus type 1-induced syncytium formation is a member of a new family of
      transmembrane proteins including CD9, CD37, CD53, and CD63.
AB  - C33 Ag was originally identified by mAb inhibitory to syncytium formation induced
      by human T cell leukemia virus type 1. The Ag was shown to be a highly
      heterogeneous glycoprotein consisting of a 28-kDa protein and N-linked
      oligosaccharides ranging from 10 to 50 kDa. In the present study, cDNA clones
      were isolated from a human T cell cDNA expression library in Escherichia coli by
      using mAb C33. The identity of cDNA was verified by immunostaining and
      immunoprecipitation of transfected NIH3T3 cells with mAb. The cDNA contained an
      open reading frame of a 267-amino acid sequence which was a type III integral
      membrane protein of 29.6 kDa with four putative transmembrane domains and three
      putative N-glycosylation sites. The C33 gene was found to belong to a newly
      defined family of genes for membrane proteins, such as CD9, CD37, CD53, CD63, and
      TAPA-1, and was identical to R2, a cDNA recently isolated because of its strong
      up-regulation after T cell activation. Availability of mAb for C33 Ag enabled us
      to define its distribution in human leukocytes. C33 Ag was expressed in CD4+ T
      cells, CD19+ B cells, CD14+ monocytes, and CD16+ granulocytes. Its expression was
      low in CD8+ T cells and mostly negative in CD16+ NK cells. PHA stimulation
      enhanced the expression of C33 Ag in CD4+ T cells by about 5-fold and in CD8+ T
      cells by about 20-fold. PHA stimulation also induced the dramatic size changes in
      the N-linked sugars previously shown to accompany human T cell leukemia virus
      type 1-induced transformation of CD4+ T cells.

PMID- 1401921
TI  - Regulation of transcription of the germ-line Ig alpha constant region gene by an
      ATF element and by novel transforming growth factor-beta 1-responsive elements.
AB  - Inasmuch as transcription of unrearranged, or germ-line, Ig CH genes appears to
      direct switch recombination, understanding the regulation of this transcription
      is essential for understanding the regulation of class switching. Transforming
      growth factor-beta 1 (TGF-beta 1) induces germ-line alpha transcripts and
      increases class switching to IgA in the I.29 mu B lymphoma and in Peyer's patch
      and splenic B cells. It has been previously demonstrated that induction of germ
      line alpha transcripts by TGF-beta occurs at the transcriptional level in I.29 mu
      cells. We now demonstrate that the DNA segment located 5' to the initiation sites
      of germ-line alpha RNA drives expression of a luciferase reporter gene construct
      in transient transfection experiments. Full constitutive expression requires no
      more than 106 bp of the 5' flanking segment. By creating a series of deletion and
      substitution mutations, we have demonstrated that an ATF/CRE site residing within
      this region is very important for constitutive expression of the germ-line alpha
      promoter, but mutation of this motif does not diminish TGF-beta induction.
      Inducibility by TGF-beta requires additional sequences residing between -128 to 
      106 relative to the first RNA initiation site. Two copies of a tandemly repeated
      sequence 5' CA-CAG(G)CCAGAC 3' (termed Ig alpha TGF-beta-RE) are located in the
      region from -127 to -105. An oligonucleotide containing multimers of these
      repeats confers TGF-beta inducibility to a heterologous promoter. An additional
      copy of the TGF-beta-RE was identified at -41/-30 and its deletion reduces the
      TGF-beta response. Thus, we conclude that tandem repeats of a novel TGF-beta-RE
      are the positive regulatory element for the TGF-beta response. Our study provides
      further evidence that TGF-beta directs class switching to IgA through induction
      of transcription of the germ-line C alpha gene and demonstrates that TGF-beta can
      activate the promoter for the germ-line alpha gene.

PMID- 1401922
TI  - Independent and synergistic effects of disulfide bond formation, beta 2
      microglobulin, and peptides on class I MHC folding and assembly in an in vitro
      translation system.
AB  - We have examined the post-translational processing, intrachain disulfide bond
      formation, folding, and assembly of MHC class I H chains with beta 2
      microglobulin after coupled in vitro translation of homogeneous mRNA and
      transport of nascent chains into canine microsomal vesicles. The formation of
      native alpha 3 domain conformation was dependent on conditions that optimized
      intrachain disulfide bond formation, and efficient folding of the alpha 1 alpha 2
      domain required exposure to antigenic peptide. beta 2-microglobulin and peptide
      acted synergistically in forming native alpha 1 alpha 2 domain structure, and a
      small proportion of molecules with native alpha 1 alpha 2, but non-native alpha 3
      structure were detected, indicating that alpha 3 domain folding is not an
      absolute prerequisite for the formation of native alpha 1 alpha 2 domain
      structure.

PMID- 1401923
TI  - The HLA-E gene encodes two differentially regulated transcripts and a cell
      surface protein.
AB  - An HLA-E-specific oligonucleotide probe was used to study the expression of HLA
      E. This probe detects two HLA-E transcripts, 1.8 and 2.7 kb in size, which are
      present in varying ratios in all tissues and cell lines investigated. We
      demonstrate that alternative poly(A) site usage accounts for the differential
      regulation of the two HLA-E mRNA species. Sequence analysis of three cDNA clones,
      representing the two transcripts of HLA-E, and of an HLA-E gene encoded by cosmid
      cd3.14, revealed identity of gene and cDNA in the 3' untranslated region. S1
      nuclease protection assays confirmed that the two HLA-E transcripts are not
      alternative splicing products. Introduction of cd3.14, together with human beta 2
      m into the murine myeloma cell line P3X63-Ag8.653, resulted in a cell surface
      expression of an HLA-class I heavy chain detectable by indirect
      immunofluorescence whereas transfection into the human beta 2m expressing mouse L
      cell line, J27 was negative with regard to cell surface expression. Cell surface
      labeling of transfectants and immunoprecipitation with a monomorphic HLA class I
      specific antibody or an antibody against human beta 2m confirmed the presence of
      an HLA-E H chain on the cell surface. These results indicate that the HLA-E gene
      codes for a class I H chain that can be expressed on the cell surface.

PMID- 1401918
TI  - Characterization of gamma delta T lymphocytes at the maternal-fetal interface.
AB  - A specific subset of gamma delta T lymphocytes bearing a V gamma 6V delta 1
      encoded TCR is known to populate the normal nonpregnant murine uterine and
      vaginal epithelium. However, gamma delta T lymphocytes residing at the maternal
      fetal interface during pregnancy have not yet been investigated. Using mAb and
      cytofluorographic analysis, we analyzed gamma delta TCR-bearing lymphocytes
      obtained from placental/decidual tissues of allogeneic (C57B1/10 X BALB/c and
      BALB/c X C57B1/10) pregnancies. Gestations were analyzed at several time points
      during the second half of pregnancy, with lymphocytes from both maternal spleen
      and nonpregnant C57B1/10 uteri analyzed as controls. We found that all gamma
      delta T lymphocytes at the maternal-fetal interface are maternally derived.
      Relative to the total T lymphocyte population, the percentage of gamma delta TCR
      bearing T lymphocytes at the maternal-fetal interface is enriched three- to four
      fold compared with maternal spleen, and twofold compared with nonpregnant uteri.
      Although one-third of gamma delta T lymphocytes from pregnant animals express a
      cell-surface marker associated with activation (IL-2R), gamma delta cells from
      uteri of nonpregnant mice fail to express IL-2R. In terms of absolute numbers, we
      estimate that reproductive-tract gamma delta T cells are increased nearly 100
      fold in pregnant animals compared with nonpregnant animals. To characterize the
      TCR-gamma delta repertoire in the placenta/decidua, we generated 21 TCR-gamma
      delta-bearing hybridomas from lymphocytes in this tissue. Analysis of these
      hybridomas revealed at least six distinct gamma delta receptor types expressed at
      the maternal-fetal interface, with V gamma 6V delta 1 encoded TCR representing
      the predominant population. As specific resident constituents of the reproductive
      tract, gamma delta T lymphocytes may be involved in regulating a variety of
      physiologic and pathophysiologic events in reproductive biology.

PMID- 1401920
TI  - Long term expression of IL-4 in vivo using retroviral-mediated gene transfer.
AB  - Th cell subsets regulate immune responses by cell-cell interaction and secretion
      of cytokines. IL-4 is one of the cytokines secreted by Th cells important for
      cellular and humoral, particularly IgG1 and IgE responses. To study the role of
      IL-4 in T cell development and regulation of immune responses in vivo, low IgE
      responder C57BL/6 mice were reconstituted with bone marrow cells that had been
      infected with recombinant retrovirus expressing a high level of IL-4. The
      reconstituted mice expressed retroviral IL-4 transcripts (9/10) even 8 mo
      postreconstitution. Physiologically significant levels of IL-4 were detected in
      the majority of the provirus-positive animals tested (5/8). Ectopic expression of
      exogenous IL-4 in hematopoietic cells had dramatic effects on T cell development
      resulting in changes in CD4:CD8 ratios. Moreover, the levels of serum IgG1 and,
      with antigenic stimulation, IgE were also increased. These results demonstrate
      that the retrovirus gene transfer system can be used to study the effects of
      ectopic cytokine gene expression in vivo on Ig isotype regulation and T helper
      cell subset differentiation.

PMID- 1401924
TI  - Leukoregulin, a T cell-derived cytokine, induces IL-8 gene expression and
      secretion in human skin fibroblasts. Demonstration and secretion in human skin
      fibroblasts. Demonstration of enhanced NF-kappa B binding and NF-kappa B-driven
      promoter activity.
AB  - It was shown previously that leukoregulin (LR), a T cell-derived cytokine with
      unique antitumor properties, modulates fibroblast functions in vitro, including
      prostaglandin production, matrix synthesis, and protease gene expression. Here,
      we have focused on the ability of LR to modulate IL-8 gene expression in human
      dermal fibroblasts. Using a specific ELISA, we demonstrated a dose-dependent
      enhancement of IL-8 production by LR, accompanied by a parallel elevation of the
      corresponding mRNA levels, as measured by Northern hybridizations. Maximum
      accumulation of IL-8 mRNA was observed after 6 h of incubation with LR, and the
      elevation persisted over 24 h. Inhibition of protein synthesis by cycloheximide
      resulted in superinduction of IL-8 mRNAs by LR. Dexamethasone, all-trans-retinoic
      acid, and TGF-beta 1 failed to counteract the effect of LR on IL-8 gene
      expression. Transient cell transfections with an IL-8 promoter/CAT reporter gene
      construct showed a dose-dependent enhancement of the promoter activity by LR,
      suggesting transcriptional regulation. Gel shift assays with oligonucleotides
      containing the consensus NF-kappa B binding sequences of the IL-8 and Ig kappa
      light chain genes showed enhanced binding activity in nuclear extracts from cells
      incubated with LR. Transient transfection experiments using a NF-kappa B/SV2
      promoter-CAT reporter gene construct showed enhanced CAT activity by LR. Taken
      together, these data suggest that LR may up-regulate IL-8 gene expression by
      activation of the binding of NF-kappa B to the corresponding cis-acting element
      in the IL-8 promoter. Our results demonstrate that LR, together with IL-1 and TNF
      alpha, could participate in the recruitment of neutrophils to the sites of
      inflammation by induction of IL-8 production in fibroblasts.

PMID- 1401925
TI  - IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the
      development of cytolytic potential by Th1 or Th2 human T cell clones.
AB  - The cytolytic potential of a total number of 118 CD4+ human T cell clones
      specific for purified protein derivative (PPD) from Mycobacterium tuberculosis,
      tetanus toxoid, Lolium perenne group I allergen (Lol p I), Poa pratensis group IX
      allergen (Poa p IX), or Toxocara canis excretory/secretory antigen(s) (TES) was
      assessed by both a lectin (PHA)-dependent and a MHC-restricted lytic assay and
      compared with their profile of cytokine secretion. The majority of clones with
      Th1 or Th0 cytokine profile exhibited cytolytic activity in both assays, whereas
      Th2 clones usually did not. There was an association between the cytolytic
      potential of T cell clones and their ability to produce IFN-gamma, even though
      IFN-gamma produced by T cell clones was not responsible for their cytolytic
      activity. IL-4 added in bulk culture before cloning inhibited not only the
      differentiation of PPD-specific T cells into Th1-like cell lines and clones, but
      also the development of their cytolytic potential. The depressive effect of IL-4
      on the development of PPD-specific T cell lines with both Th1 cytokine profile
      and cytolytic potential was dependent on early addition of IL-4 in bulk cultures.
      In contrast, the addition in bulk culture of IFN-gamma enhanced both the
      cytolytic activity of PPD-specific T cell lines, as well as the proportion of PPD
      specific T cell clones with cytolytic activity. The addition in bulk cultures
      before cloning of IFN-gamma or IFN-alpha favored the development of TES-specific
      and Poa p IX-specific T cells into T cell clones showing a Th0 or even a Th1,
      rather than a Th2, cytokine profile. Accordingly, most of TES- and Poa p IX
      specific T cell clones derived from cultures containing IFN-gamma or IFN-alpha
      displayed strong cytolytic activity. These data indicate that the majority of
      human T cell clones that produce IFN-gamma, but not IL-4 (Th1-like), as well as
      of T cell clones that produce IFN-gamma in combination with IL-4 (Th0-like) are
      cytolytic. More importantly, they demonstrate that the addition of IFN (alpha and
      gamma) or IL-4 in bulk cultures before cloning may influence not only the
      cytokine profile of human CD4+ T cell clones but also their cytolytic potential.

PMID- 1401926
TI  - Kinetic analysis of cytokine gene expression in the livers of naive and immune
      mice infected with Listeria monocytogenes. The immediate early phase in innate
      resistance and acquired immunity.
AB  - The anamnestic response to infection with Listeria monocytogenes is characterized
      by the rapid elimination of normally lethal doses of bacteria and accelerated
      granuloma formation. These phenomena are mediated by listeria-specific memory T
      cells within the first 24 h after reinfection. In order to elucidate the
      mechanisms operative during this decisive phase of infection, we conducted a
      comprehensive kinetic and quantitative analysis of cytokine gene expression in
      the livers of naive and immune mice. Organs were removed at 30 min, and 1, 2, 6,
      and 24 h after primary and secondary infections, and PCR3-assisted messenger RNA
      (mRNA) amplification was performed on matched samples using primers specific for
      IL-1 beta, IL-6, M-CSF, GM-CSF, TNF-alpha, IFN-gamma, IL-10, IL-4, IL-2, IL-3 and
      I1-2Rp55. The cytokine pattern characteristic of secondarily infected animals
      differed qualitatively by the expression of mRNA for IL-2, IL-2Rp55, IL-3, and IL
      4, demonstrating the accumulation and activation of specific T cells in the
      livers as early as 1 to 2 h after reinfection. Combined in vivo depletion of both
      CD4+ and CD8+ T cells before reinfection almost completely abrogated the
      differentiated cytokine profile typical of the anamnestic response. Using
      competitive PCR for semiquantitative determination of mRNA levels, the amount of
      IL-1 beta and IL-6 mRNA was found to be very similar during primary and secondary
      infection, whereas TNF-alpha mRNA was found to be increased by approximately 10
      fold 2 h and IFN-gamma mRNA by approximately 50 to 100-fold 6 h after reinfection
      when compared with a primary challenge. Combined in vivo depletion of both CD4+
      and CD8+ T cells before reinfection resulted in a substantial (approximately 10
      fold) decrease in IFN-gamma mRNA expression. To correlate these findings with
      cytokine secretion, spleen cells from naive and immune as well as normal and CD4+
      and CD8+ cell depleted mice infected 6 h previously were cultured for 48 h, and
      supernatants were analyzed for the amount of the above mentioned cytokines.
      Semiquantitative PCR-assisted mRNA amplification is demonstrated to be a superior
      tool in dissociating the mediators of innate resistance from those operative in
      protective immunity and granuloma formation.

PMID- 1401927
TI  - IFN-gamma and IL-2 are protective in the skin but pathologic in the corneas of
      HSV-1-infected mice.
AB  - HSV type 1 (HSV-1) infection of the mouse cornea results in a tissue-destructive
      inflammatory reaction in the cornea, but little or no disease in the skin
      surrounding the eye. Depleting T lymphocytes from mice before HSV-1 corneal
      infection prevents the corneal inflammation but severely exacerbates the
      periocular skin lesions. Studies described in this communication investigated the
      role of T cell cytokines in the corneal and periocular skin disease induced by
      HSV-1 corneal infection. Mice received weekly i.p. injections of rat mAb specific
      for IL-2, IL-4, or IFN-gamma beginning 1 day before (day -1) or 6 days after (day
      +6) corneal infection with the RE strain of HSV-1. The severity of corneal
      inflammation and the area of periocular skin involvement were measured. Treatment
      with anti-IFN-gamma or anti-IL-2 significantly reduced the incidence and severity
      of corneal inflammation. Treatment was equally effective when initiated on day -1
      (before T cell activation) or day +6 (after T cell activation but before the
      initiation of corneal inflammation). Treatment with anti-IL-4 had no effect. The
      histologic features of corneal inflammation in mock-treated mice included
      neovascularization, corneal edema, and cellular infiltration. Corneas of anti-IL
      2-treated mice that developed inflammation had similar but less severe histologic
      features. Corneas of anti-IFN-gamma-treated mice that developed inflammation had
      neovascularization and edema but minimal cellular infiltration. Treatment with
      anti-IFN-gamma or anti-IL-2 significantly exacerbated periocular skin lesions
      when initiated at day -1, but not when initiated at day +6. Anti-IL-4 treatment
      had no effect on skin lesions. Treatment with either anti-IFN-gamma or anti-IL-2,
      when initiated at day -1, significantly inhibited the delayed-type
      hypersensitivity response to HSV Ag, but when treatment was begun at day +6 only
      anti-IFN-gamma significantly inhibited the delayed-type hypersensitivity
      response. Our findings suggest that IFN-gamma and IL-2 are important elements in
      both an immunopathologic T-lymphocyte response to HSV-1 Ag in the cornea and a
      protective T lymphocyte response in the skin.

PMID- 1401928
TI  - Biochemical and immunologic characterization of a major IgE-inducing filarial
      antigen of Brugia malayi and implications for the pathogenesis of tropical
      pulmonary eosinophilia.
AB  - A major allergen of the human filarial parasite Brugia malayi has been identified
      by two-dimensional immunoblot analysis using a serum pool from patients with
      tropical pulmonary eosinophilia. The allergen is composed of two Ag with M(r) 23
      and M(r) 25 and acidic isoelectric point (Bm23-25). Immunoblots using affinity
      purified IgE antibodies to BM23-25 indicated that Bm23-25 is expressed mainly in
      the microfilarial stage. Digestion of the allergen with endoglycosidases
      indicates that it has N-linked oligosaccharide chains. Analysis of the reactivity
      of T cells derived from patients with lymphatic filariasis revealed that the Bm23
      25 allergen was capable of stimulating T cell proliferation; Bm23-25 was also
      shown to induce IgE production in vitro from PBMC derived from patients with
      either TPE or other filarial symptoms. Bronchoalveolar lavage fluid of patients
      with TPE contained IgE antibodies that recognized Bm23-25 strongly, an
      observation suggesting that the microfilarial allergen might be involved in the
      pathogenesis of the TPE syndrome.

PMID- 1401929
TI  - Cytokine expression in vivo during murine listeriosis. Infection with live,
      virulent bacteria is required for monokine and lymphokine messenger RNA
      accumulation in the spleen.
AB  - To examine the regulation of cytokine synthesis during murine listeriosis, we
      have monitored IFN-gamma, TNF-alpha, and IL-1 beta mRNA levels in the spleens of
      C57B1/6 mice after the i.v. infusion of virulent and nonvirulent preparations of
      Listeria monocytogenes (LM). Messenger RNA coding for TNF, IL-1, or IFN did not
      become detectable until approximately 12 to 15 h after the infusion of virulent
      LM. Levels of each cytokine mRNA then increased synchronously reaching peak or
      near peak levels around 24 h after infection. Levels gradually decreased over the
      next 4 to 5 days. Unlike virulent LM, neither heat-killed LM, nor nonvirulent LM
      variants lacking listeriolysin O, stimulated monokine or IFN mRNA accumulation
      even when administered in very large doses. To gain perspective concerning the
      response to LM, we examined the early pattern of cytokine mRNA accumulation
      induced by Salmonella typhimurium (ST), an intracellular pathogen expressing LPS.
      We noted at least three significant differences between the cytokine responses to
      LM and ST: 1) monokine mRNA levels increased much more rapidly (within 1 h) after
      ST infection; 2) unlike LM, ST retained the capacity to stimulate cytokine mRNA
      production when injected as heat-killed bacteria; 3) in contrast to LM, ST could
      not trigger the early IFN production characteristic of LM infection. Our data
      suggest that monokine and IFN production early in listeriosis are critically
      linked with the process of bacterial invasion of host cells. The timing and
      pattern of cytokine mRNA accumulation in this setting is qualitatively different
      from that induced by LPS. The pathway described in these studies may also play a
      role in the host cytokine response to other intracellular pathogens as well.

PMID- 1401930
TI  - Lipopolysaccharide induces Egr-1 mRNA and protein in murine peritoneal
      macrophages.
AB  - Bacterial LPS has diverse effects on the function of immune cells, in general,
      and macrophages, in particular. The intracellular molecular events that mediate
      the effects of LPS are unclear. We undertook a series of studies in
      thioglycollate-elicited murine peritoneal macrophages to evaluate the effect of
      LPS on expression of Egr-1, a member of the immediate early response gene family.
      Egr-1 may function as an intranuclear "third messenger" because it is rapidly
      induced in a variety of cell types and encodes a 75- to 80-kDa nuclear
      phosphoprotein that activates transcription of genes containing the DNA consensus
      sequence GCGGGGGCG. LPS from Salmonella minnesota Re595 induced a maximal
      increase in Egr-1 mRNA in macrophages after 30 to 60 min of incubation that
      returned to baseline level by 120 min. LPS increased Egr-1 mRNA at 0.01 to 0.1
      ng/ml with a maximal effect at 10 to 100 ng/ml. LPS markedly increased the
      transcription rate of Egr-1 by 10 min of incubation using nuclear run on
      analysis. Using a polyclonal anti-Egr-1 antibody, nuclear staining for Egr-1
      protein was prominent after 1 to 2 h of incubation with LPS and declined to
      baseline by 4 h. Inasmuch as protein kinase C (PKC) has been implicated in
      mediating the effects of LPS, we determined whether PKC was required for LPS to
      increase Egr-1 mRNA. Two pharmacologic approaches were used to deplete PKC, PMA
      pretreatment, and H-7. The induction of Egr-1 mRNA by LPS was markedly reduced in
      PKC-depleted macrophages. These data reveal that LPS induces transcriptional
      activation of Egr-1 and increases Egr-1 protein in peritoneal macrophages. In
      addition, these findings support further study of the potential role of Egr-1 in
      mediating the effects of LPS in peritoneal macrophages.

PMID- 1401931
TI  - Macrophage and monocyte IL-1 beta regulation differs at multiple sites. Messenger
      RNA expression, translation, and post-translational processing.
AB  - Maturation of blood monocytes into macrophages is accompanied by a number of
      functional changes including decreased IL-1 beta release in response to LPS. This
      limitation has previously been ascribed to transcriptional regulation. However,
      in seeming conflict with the observed depression in IL-1 beta mRNA levels, recent
      work demonstrates increased intracellular IL-1 beta in macrophages. Therefore,
      the present study sought to explain these differences by comparing IL-1 beta
      production from autologous alveolar macrophage and blood monocyte pairs at
      multiple regulatory sites, including endotoxin responsiveness, mRNA expression,
      protein translation, and post-translational processing. Macrophages did not
      differ from monocytes in endotoxin sensitivity, but when analyzed by both ELISA
      and Western blot, were confirmed to have limitations in IL-1 beta release. Gene
      expression studies demonstrated that at 4 h, macrophage IL-1 beta steady state
      mRNA levels were 3-fold lower than the monocyte's. However, total IL-1 beta
      protein production, as measured by [35S]methionine labeling with
      immunoprecipitation, demonstrated three- to sixfold higher amounts in macrophages
      at comparable time points. The enhanced protein production in the face of
      relatively low mRNA levels suggests that macrophages translate IL-1 beta mRNA
      more efficiently. Furthermore, characterization of IL-1 beta release into
      supernatants revealed that whereas monocyte release occurred early, represented 5
      to 20% of the intracellular amounts, and contained largely processed IL-1 beta,
      macrophage release was delayed, represented 1 to 5% of the intracellular amounts,
      and contained primarily unprocessed IL-1 beta. Taken together, these data
      demonstrate that the limitations in alveolar macrophage IL-1 beta release occur
      due to slower export and conversion of 35- to 17-kDa protein and are not due to
      differences in sensitivity to endotoxin or to transcriptional control mechanisms.

PMID- 1401932
TI  - Detection of alveolar macrophage-derived IL-1 beta in asthma. Inhibition with
      corticosteroids.
AB  - This study investigated alveolar macrophage function in asthma as assessed by the
      presence and source of the cytokine IL-1 beta. Bronchoalveolar lavage (BAL) fluid
      and cell pellets were obtained at 4 a.m. from a cohort of asthmatic subjects.
      Normal subjects were used as controls. Asthmatic BAL fluid contained 57.0 +/- 5.9
      pg/ml of IL-1 beta as determined by ELISA. No IL-1 beta could be identified in
      the BAL fluid of the control group. This IL-1 represented synthesis by cells of
      the airway as assessed by the presence of IL-1 beta-specific mRNA transcripts in
      the BAL cell pellets. Inasmuch as IL-1 beta transcripts are known to be present
      for only a short time period after activation (approximately 0.5 to 16 h), the
      presence of transcripts represents recent cellular activation. Using the
      technique of in situ hybridization, IL-1 beta transcripts were found to be
      located exclusively within alveolar macrophages, and a mean of 40 +/- 14% of
      alveolar macrophage were activated at the time of the lavage. Corticosteroids are
      known to be efficacious in the treatment of asthma. Administration of a single 50
      mg dose of prednisone at 3 p.m. resulted in diminished IL-1 beta protein
      concentration in the BAL fluid (28.3 +/- 5.7 pg/ml; p < 0.01 compared to
      baseline) and completely abrogated IL-1 beta mRNA expression. In summary, these
      studies demonstrate that IL-1 beta is synthesized within the airways by alveolar
      macrophage and suggest that IL-1 beta may be a mediator of asthma. Inhibition of
      IL-1 beta may be an additional mechanism for the efficacy of corticosteroids in
      the treatment of asthma.

PMID- 1401933
TI  - Structure and binding properties of a monoclonal anti-idiotypic autoantibody to
      anti-DNA with epibody activity.
AB  - We report the isolation and characterization of a mouse autoanti-idiotypic mAb
      (D7.4 IgG2a), which is directed against a major public Id (A52 IgG2b) in the
      murine and human autoimmune response to DNA. The natural anti-Id mAb has been
      produced in the course of the SLE-like disease in a female NZB/NZW F1 mouse and
      showed a dual specificity (epibody activity) for the public Id (A52) and for the
      autoantigen (DNA). The two binding activities were shown to reside in the Fab
      portion of the epibody and were highly specific for their respective Ag. A
      complete nucleotide sequence analysis of the D7.4 H and L chain V-region genes
      combined with computer comparisons to available Ig sequences may suggest a charge
      interaction between the H chain CDR3 segments of the Id and anti-Id antibodies.
      The D7.4 epibody may be a component of the self-binding, idiotypically connected
      network of natural antibodies. Alternatively, it could be elicited against the
      potentially pathogenic, DNA-containing immune complexes in order to facilitate
      their removal from the circulation of diseased individuals.

PMID- 1401934
TI  - Novel deletion and a new missense mutation (Glu 217 Lys) at the catalytic site in
      two adenosine deaminase alleles of a patient with neonatal onset adenosine
      deaminase- severe combined immunodeficiency.
AB  - Mutations at the adenosine deaminase (ADA) locus result in a spectrum of
      disorders, encompassing a fulminant neonatal onset severe combined
      immunodeficiency (SCID) and childhood onset immunodeficiency, as well as
      apparently normal immune function. The extent of accumulation of the toxic
      metabolite, deoxyATP, correlates directly with severity of disease. We have now
      determined the mutations on both alleles of a child with fulminant, neonatal
      onset ADA- SCID and accumulation of extremely high concentrations of deoxyATP.
      The genotype was consistent with the severely affected phenotype. One allele
      carried a large deletion that arose by non-homologous recombination and included
      the first five exons and promoter region. The second allele carried a missense
      mutation (G649A) resulting in replacement of Glu217, an amino acid involved in
      the catalytic site, by Lys and predicting a major alteration in charge.
      Expression of the mutant cDNA in Cos cells confirmed that the mutation abolished
      enzyme activity. We have previously reported that a missense mutation at the
      preceding codon is similarly associated with neonatal onset ADA- SCID and
      accumulation of extremely high deoxyATP. These findings suggest that genotype
      phenotype correlations may be apparent for ADA- SCID, despite the role that
      random variation in exposure to environmental pathogens may play in the initial
      phenotype. Such genotype-phenotype correlations may be important to consider in
      evaluating results of ongoing trials of "gene" and enzyme replacement therapy.

PMID- 1401935
TI  - The use of nylon wool for the isolation of T lymphocyte subpopulations.
AB  - A simple method for the affinity isolation of lymphocyte subpopulations using
      nylon wool as a solid phase matrix is described. This matrix was coated with an
      acid-treated IgG fraction of polyclonal antibodies against mouse immunoglobulins.
      Using this approach, a simple isolation procedure for lymphocyte subpopulations,
      yielding purities higher than 95% was developed. The method can be used on a
      large scale for positive and negative cell selection, with very little non
      specific binding. The isolated populations are fully functional.

PMID- 1401936
TI  - Effective blocking of natural cytotoxicity of young rabbit serum on murine
      thymocytes by high concentration of glucose in complement-dependent cytotoxicity
      method.
AB  - By an accidental observation, the natural cytotoxicity of 21-day-old rabbit sera
      to murine thymocytes was found to be almost completely inhibitable by 4.5 mg/ml
      glucose. This enabled us to use unabsorbed young rabbit serum as a source of
      complement for antibody-mediated cytotoxic treatment of murine thymocytes. This
      glucose-sensitive natural cytotoxic activity was recovered in the immunoglobulin
      fraction purified on an affinity column, and was dependent on complement
      activity. The unabsorbed 21-day-old rabbit sera had much higher complement
      activity than those from 14-day-old rabbits and commercially available low
      background complement. Indeed, complete depletion of CD4+ cells from murine
      thymocytes and splenocytes was achieved using unabsorbed 21-day rabbit serum as a
      source of complement and a monoclonal antibody GK1.5 which has been claimed to be
      inefficient in complement-dependent killing. Owing to the increase in complement
      titer and circulating blood volume 14-21 days after birth, the use of 21-day-old
      rabbit sera assures a much more abundant supply of complement for the treatment
      of murine lymphocytes.

PMID- 1401937
TI  - The detection of intracytoplasmic interleukin-1 alpha, interleukin-1 beta and
      tumour necrosis factor alpha expression in human monocytes using two colour
      immunofluorescence flow cytometry.
AB  - Two colour flow cytometry was used to analyse in situ cytokine expression by
      human monocytes. Whole blood was cultured in siliconised glass bottles, with or
      without E. coli lipopolysaccharide (LPS), for various times, and the mononuclear
      cells (MNCs) then exposed to a variety of permeabilisation procedures prior to
      flow cytometric analysis. Paraformaldehyde (PF)/saponin fixation preserved
      cellular morphology, and caused a reproducible degree of permeabilisation
      (estimated by propidium iodide inclusion: mean 94%, range 86-99% (n = 33)). After
      fixation with 4% PF and permeabilisation with 1% saponin at 0 degrees C in PBS
      containing 20% human serum, MNCs were incubated with phycoerythrin(PE)-conjugated
      mouse anti-CD14 (monocyte phenotype) and polyclonal rabbit anti-human interleukin
      1 alpha (IL-1 alpha), IL-1 beta, tumour necrosis factor alpha (TNF-alpha), or
      control rabbit IgG. Binding of rabbit antibodies was detected using goat anti
      rabbit IgG fluorescein isothiocyanate (FITC). FITC fluorescence was increased in
      CD14 PE positive cells with the three anti-cytokine antibodies following LPS
      stimulation, compared with controls. There was a reproducible dose related
      response in monocyte IL-1 beta and TNF-alpha expression following LPS
      stimulation, with early peaks in TNF-alpha (2 h), compared with IL-1 beta (4 h),
      and IL-1 alpha (12 h). Specificity of this cytokine detection system was
      confirmed by inhibition studies using the corresponding recombinant human
      cytokines, by an absence of staining in CD14 negative or unpermeabilised MNCs,
      and by the characteristic cytoplasmic localisation of the different cytokines
      visualised with UV immunochemistry. Hence, the methods described here provide a
      reproducible, semiquantitative and specific assay for the detection of cell
      associated monokines. The technique may be applicable to the analysis of a
      variety of different cytokines in other phenotypically defined cell populations.

PMID- 1401939
TI  - A transient transfection system for identifying biosynthesized proteins processed
      and presented to class I MHC restricted T lymphocytes.
AB  - CD8+ cytotoxic T lymphocytes (CTL) constitute a major portion of immune responses
      to foreign and self antigens. CTL recognize class I major histocompatibility
      complex molecules complexed to peptides of 8-10 residues derived from cytosolic
      proteins. To understand CTL responses to these antigens and to manipulate CTL
      responses optimally, it is necessary to identify the specific peptides recognized
      by CTL. The methods currently used for this purpose have significant drawbacks.
      We describe a plasmid transfection method that results in significant lysis of
      histocompatible target cells. Influenza virus-specific CTLs specifically lysed
      target cells that were transfected with plasmids bearing cDNAs encoding full
      length gene products, fragments containing the region that encodes the CTL
      epitope, or even a ten residue peptide. This significantly lessens the time and
      effort required to define genes, and gene segments that contain CTL epitopes.

PMID- 1401938
TI  - A rapid and sensitive cellular enzyme-linked immunoabsorbent assay (CELISA) for
      the detection and quantitation of antibodies against cell surface determinants.
      I. A comparison of cell fixation and storage techniques.
AB  - A solid phase cellular ELISA was designed and evaluated for the detection of
      antibodies specific for cell surface determinants. It was hypothesized that
      certain fixation and freezing procedures would result in stabilization of cell
      structures for prevention of antigen diffusion and extraction during washing
      procedures. This would assure assay accuracy and convenient sample management. It
      was hypothesized that fixation with certain reagents prior to analysis would not
      alter antigenicity of antibody targeted epitopes. In order to improve the
      preservation of the cells following cell binding to the solid phase matrix while
      still retaining antigenicity and morphology, a series of fixatives and storage
      procedures were screened to determine which were best suited for CELISA.
      Methanol, washing buffer (WB), Hanks' balanced salt solution (HBSS), and 0.5%
      formalin in HBSS were examined by comparing their relative cell binding capacity
      and the subsequent cell morphology. In consideration of all variables, fixation
      in 0.5% formalin provided the best maintenance of cell antigenicity, morphology,
      binding, and was associated with consistent results. Cells used immediately after
      fixation and fixed cells used after storage at -80 degrees C for up to 12 months
      were compared to determine if long term storage affected antigenicity. Since
      frozen cells and fresh cells demonstrated statistically identical positive to
      negative ratios and consistency of antibody binding, it was determined that long
      term frozen storage of formalin-fixed cells did not adversely affect antibody
      binding capacity to cell surface determinants.

PMID- 1401940
TI  - Selective generation of antigen-specific human hybridomas optimized for large
      scale growth in serum-free medium.
AB  - The direct propagation of newly formed human hybridomas in serum-free medium
      selects for hybrids with a metabolism best suited to growth in this environment.
      Under optimal culture conditions, this procedure results in the generation of
      antigen-specific human hybridomas comparable in frequency, stability, and
      antibody secretion rate to that obtained with murine hybridomas. After a
      transient phase of a few days in the appropriate selection medium supplemented
      with 1% serum, hybridomas grow in serum-free medium in stationary cultures with a
      cell doubling time of 15-25 h and an antibody production rate averaging 12
      micrograms/10(6) cells/day. Clones propagated in bioreactors exhibited a cell
      doubling time of 29-35 h and an antibody secretion rate of 10-21 micrograms/10(6)
      cells/day.

PMID- 1401941
TI  - Monoclonal antibody based ELISAs for cryptococcal polysaccharide.
AB  - Mouse monoclonal antibody (MAb)-based enzyme-linked immunosorbent assays (ELISAs)
      have been developed to detect Cryptococcus neoformans capsular polysaccharide
      from the four serotypes A, B, C and D. The ELISAs avoid the problem of unreliable
      polysaccharide binding to polystyrene plates by using MAbs to capture and
      immobilize the polysaccharide antigen. The presence of polysaccharide is detected
      using MAbs of a different isotype from that of the capture MAb. The capturing
      MAbs are themselves immobilized on the plates using commercial goat anti-mouse
      polyclonal sera. The MAbs bind to the glucuronoxylomannan component of
      cryptococcal polysaccharide. The ELISAs can be used to measure the concentration
      of polysaccharide in biological fluids and are potentially useful tools for basic
      research and clinical studies.

PMID- 1401942
TI  - Analysis of high complement levels in Mus hortulanus and BUB mice.
AB  - BUB/BnJ mice were previously identified as having exceptionally potent complement
      activity, relative to common mouse strains, in the lysis of antibody-coated human
      tumor cells. We describe herein our investigation into the molecular and genetic
      basis for this difference between mouse strains, and also our results with wild
      mice and mouse strains recently derived from the wild, to determine whether low
      complement levels are characteristic of wild mice. BUB complement was compared
      with complement from BALB/c and C57BL/6 mice. BUB mice had higher levels of most
      individual classical pathway components, except for C1, than the other two
      strains, but the difference was generally only 2-3-fold, so insufficient to fully
      explain the difference observed with tumor target cells. CH50 titers on antibody
      coated sheep erythrocytes also demonstrated only a 2-4-fold difference. However,
      CH50 titers on antibody-coated human erythrocyte target cells demonstrated a
      difference similar in magnitude to that seen with human tumor targets. These
      results suggest that the difference between mouse strains depends partly on the
      use of human, rather than sheep, target cells. In an assay for alternative
      complement pathway activity using neuraminidase-treated human erythrocytes as
      targets, complements of BALB/c and BUB mice were similar in activity, suggesting
      that the difference between mouse strains is manifested in the early steps of
      complement activation. Analysis of F1 and backcross mice suggested that the
      difference in complement level between BUB and BALB/c or C57BL/6 mice is
      controlled by semi-dominant genes, and cannot be attributed to a single gene.
      Wild mice and mice recently derived from the wild generally had low complement
      levels, similar to most laboratory mice. However, three strains of aboriginal
      mice, including Mus hortulanus (spicilegus) and Mus spretus, had complement
      levels higher than that of BUB mice, and as high as sera from the rabbit or rat,
      which are the most potent known complement sources for the lysis of human tumor
      cells. In comparison with BUB mouse sera, M. hortulanus sera had at least four
      fold higher levels of C3, C6, C8 and C9, and some or all of these differences may
      explain its higher total complement activity. In the lysis of antibody-coated
      human erythrocytes, M. hortulanus serum was more potent than any other complement
      source tested, including sera of the guinea pig, rat, rabbit or human. These
      strains may be useful in investigating the role of complement in various
      pathological processes, and in investigating the genetic regulation of the
      complement system.

PMID- 1401943
TI  - Determination of the immunoreactive fraction of radiolabeled monoclonal
      antibodies directed against intracellular antigens.
AB  - For investigations involving monoclonal antibodies (mAbs) against cellular
      antigens cell binding assays are routinely used to determine the immunoreactive
      fraction after radiolabeling. In general, surface antigens are targets for
      radioimmunodetection, but recent studies indicate that intracellular determinants
      may also prove useful for this purpose. Thus, there is a need to adapt the
      regular cell binding assay for use with antibodies directed against cytoplasmic
      antigens. Here we describe a fixation method which permits such mAbs to bind to
      cell surfaces as well as to intracellular determinants. Moreover, the procedure
      may be used for antigens that are sensitive to the commonly used aldehyde
      fixatives. The method is illustrated with two human IgM mAbs 16.88 and 28A32,
      which recognize cytoplasmic antigens. Human colon cancer cells in suspension were
      fixed with either acetone or glutaraldehyde. Intracellular antigens appeared to
      be best exposed for antibody binding after fixation with acetone as determined by
      immunofluorescent staining and flow cytometry. An antibody directed against the
      cell surface antigen HLA class I showed similar binding with both live cells and
      acetone-fixed cells. Double-inverse plots of the binding of radiolabeled 16.88 or
      28A32 antibody with acetone-fixed cells gave reliable immunoreactive fraction
      values. Acetone-fixed cells stored at 4 degrees C could be used for
      immunoreactivity assays for at least 6 months without loss of performance.

PMID- 1401944
TI  - Increased specificity and sensitivity of insulin antibody measurements in
      autoimmune thyroid disease and type I diabetes.
AB  - Insulin autoantibodies (IAA), a marker for insulin-dependent diabetes mellitus
      (IDDM), have been reported in other diseases such as thyroid disease and after
      treatment with sulfhydryl containing medications. Reported prevalences of IAA in
      non-diabetics vary widely, probably due in part to methodological differences
      between laboratories. In addition, certain sera may have a high non-specific
      binding to insulin. We compared a radioimmunoassay (RIA) for IAA which included
      non-specific binding with an RIA that incorporated a competitive displacement
      with cold insulin to remove non-specific binding. Using the RIA which measured
      specific plus non-specific binding, IAA positivity was found in 22/92 (23.9%) of
      sera from thyroid disease patients, 16/124 (12.9%) of random masked sera from a
      hospital laboratory, 27/335 (8.1%) of first degree relatives of IDDM patients,
      63/178 (35.4%) of subjects with newly diagnosed IDDM, and 0/92 (0%) of normal
      controls. Insulin antibodies (IA) were found in 80/99 (80.8%) of insulin-treated
      diabetic subjects. In contrast, using the displacement assay which allowed
      measurement of specific binding, the frequency of IAA positivity was lower for
      subjects with thyroid disease (7/92 (7.6%)), random hospital sera (12/124
      (9.8%)), and for first degree relatives of IDDM patients (8/335 (2.4%)), while
      higher for subjects with newly diagnosed IDDM (71/178 (39.9%)). Subjects with
      insulin-treated diabetes (78/99 (78.8%)) and normal subjects (1/92 (1.1%)) showed
      little change. Strikingly, three of the eight (37.5%) relatives of IDDM patients
      that were positive in the RIA measuring specific binding were detected only
      because cold displacement was utilized. We conclude: (1) subjects with thyroid
      disease and first degree relatives of IDDM patients frequently have high non
      specific binding for IAA in an RIA not employing a cold displacement step, (2) in
      some newly diagnosed IDDM patients and first degree relatives of IDDM patients,
      IAA may be missed by an assay not optimized to measure specific binding, and (3)
      displacement with cold insulin increases both the specificity and sensitivity of
      RIAs measuring insulin autoantibodies.

PMID- 1401945
TI  - Use of defined oligosaccharide epitopes in an ELISA for group B streptococcus.
AB  - A single-site ELISA for group B streptococcal polysaccharide based on a
      monoclonal antibody against an immunodominant trirhamnoside epitope was inhibited
      at high capture antibody coating densities. The inhibition was eliminated when
      less antibody was coated or when high antigen concentrations were tested. This
      antigen is polyvalent with respect to the terminal trirhamnoside epitope and
      therefore it appears that closely spaced capture antibodies bound the epitope
      completely, leaving no sites for attachment of the enzyme-labeled second antibody
      with the same specificity. To make use of the trirhamnoside epitope feasible, a
      two-site ELISA was evaluated with this monoclonal antibody and a polyclonal
      antibody isolated by affinity chromatography. ELISA inhibition studies using
      oligosaccharides derived from the group B polysaccharide were used to evaluate
      the specificity of the polyclonal antibody. This showed that the antibody
      recognized both alpha-L-rhamnose (1----3)-D-galactose and alpha-L-rhamnose(1---
      3)-D-glucitol side chains, which together represent 30 potential binding sites
      per antigen molecule. A two-site ELISA with the anti-trirhamnoside monoclonal
      antibody to capture the antigen and the polyclonal antibody as enzyme conjugated
      second antibody reacted with only group B streptococci when tested against a
      panel of bacteria representative of the vaginal flora and was able to detect 3 x
      10(4) cfu/test of group B streptococci. This two-site ELISA, based on well
      defined oligosaccharide epitopes had the sensitivity and specificity necessary to
      identify women at risk of infecting their newborns with group B streptococcus.

PMID- 1401947
TI  - Microplate washing: process description and improvements.
AB  - Heterogeneous immunoassays require wash steps in order to separate bound from
      free constituents. In this paper we demonstrate that in microplate assays the
      washing process includes two separate physical processes: (1) a rapid and wash
      volume-dependent direct dilution of the droplet-shaped residual volume, and (2) a
      diffusion-limited and strongly time-dependent dilution of a residual layer of
      liquid, which necessitates the use of time-consuming soak times in the
      immunoassay. We have shown that optimizing the motion of the wash fluid
      effectively reduces the residual layer thickness that results in extended soak
      times. This results not only in improved washing efficiency and reduced
      background variance in the immunoassay, it also yields a significantly improved
      immunoassay sensitivity.

PMID- 1401946
TI  - Lymphocyte immunophenotyping by flow cytometry in normal adults. Comparison of
      fresh whole blood lysis technique, Ficoll-Paque separation and cryopreservation.
AB  - In the present report we have assessed the extent to which Ficoll-Paque
      separation and cryopreservation of mononuclear cells alter the measurement of
      lymphocyte subsets by flow cytometry. Standard Ficoll-Paque separation increased
      the percentage of CD4+, CD19+ and CD4+CD45RA+ cells, as well as decreasing that
      of CD8+, and CD4+CD29+ cells, compared to the fresh whole blood lysis technique.
      Moreover, cryopreservation caused a depletion of CD4+ p80+ cells, but normal
      whole blood values were restored following a short incubation.

PMID- 1401949
TI  - A simple fluorescence method for surface antigen phenotyping of lymphocytes
      undergoing DNA fragmentation.
AB  - Apoptosis, a metabolically active process of programmed cell death characterized
      by DNA fragmentation, is believed to play an important role in development of
      lymphocyte repertoires and in embryogenesis. Studies of this phenomenon would be
      greatly facilitated by the development of a simple assay capable of identifying
      and isolating intact apoptotic cells. A rapid fluorescence assay which identifies
      relatively small, intact cells containing fragmented DNA is described in this
      report. Thymocytes in which DNA fragmentation is induced by culture with or
      without dexamethasone are readily identified by their bright blue fluorescence
      after a 15 min treatment with Hoechst 33342, a DNA binding fluorochrome which
      diffuses through cell membranes. Since Hoechst 33342 staining does not require
      destruction of the cell membrane, it is possible to directly phenotype cell
      surface antigen expression on Hoechst 33342bright lymphocytes by conventional
      immunofluorescence techniques and to evaluate membrane integrity of Hoechst
      33342bright cells by dye exclusion criteria. The advantages of this system are
      that it: (1) is rapid and simple, (2) quantitates the percentage of cells
      fragmenting their DNA and presumably undergoing apoptosis, (3) permits standard
      immunofluorescence staining of cell surface markers to identify even minor cell
      subsets of presumably apoptotic cells within heterogeneous populations, (4)
      provides the tools (fluorescence activated cell sorting) for purifying intact
      cells containing fragmented DNA for further biochemical studies, and (5) provides
      a means for identifying cells which exclude vital dyes and in which DNA
      fragmentation will eventually result in cell death.

PMID- 1401948
TI  - The development of enzyme-linked immunosorbent assays (ELISA) for the
      catecholamines adrenalin and noradrenalin.
AB  - Monoclonal antibodies have been raised against adrenalin and noradrenalin and
      used as the basis of enzyme-linked immunosorbent assays (ELISA) to detect and
      estimate the concentrations of these catecholamines. Inhibition assays are
      described, with sensitive quantification in the range from 1 mg/ml to 100 pg/ml.
      Cross-reactivity assays reveal that neither assay is subject to interference by
      catecholamine metabolites at concentrations less than 100 ng/ml and 1
      micrograms/ml respectively. Isolation and quantification of both catecholamines
      from clinical samples is discussed and the potential application of these ELISAs
      in a clinical setting is proposed.

PMID- 1401950
TI  - A quantitative objective method for the evaluation of anti-sperm cell-mediated
      immunity in humans.
AB  - Anti-sperm cell-mediated immunity (CMI) is considered as a crucial facet of
      infertility in patients of both sexes. A precise and objective method is
      designed, based on a one-step agarose leukocyte migration inhibition factor
      (LMIF) assay. The migration areas are evaluated by a computer-assisted image
      analysis system. Optimal concentrations of leukocytes and sperm, as well as
      technical conditions are described. The radial migration indexes (RMI) and area
      migration indexes (AMI) are computed and expressed as a migration index (MI)
      percentage for each patient or control. Preliminary clinical results indicate a
      highly significant association between migration inhibition and cases of
      'immunopathological infertility'. The method described is considered a promising
      tool for a rapid and quantitative evaluation of a suspected anti-sperm CMI in
      infertile and recurrently aborting patients.

PMID- 1401951
TI  - Analysis of human IgA subclasses by in situ hybridization and combined in situ
      hybridization/immunohistochemistry.
AB  - In this report we describe a method for the analysis of the cellular expression
      of the two human IgA subclasses by in situ hybridization (ISH). The technique
      permits the detection of specific mRNA in individual cells using 35S-labeled
      oligonucleotide probes without any detectable cross-hybridization between the
      subclasses. This method was applicable both on cytospin preparation of peripheral
      blood mononuclear cells as well as in formalin-fixed, paraffin-embedded tissue
      sections. Furthermore, we describe a combined ISH/immunohistochemistry technique
      for the simultaneous detection of IgA subclass mRNA and protein at the single
      cell level. Examination of tissue sections from tonsils revealed a striking
      localization of labeled cells within the germinal center of some of the lymphoid
      follicles. The implications of this novel finding and the development of the
      method are discussed.

PMID- 1401952
TI  - Antibody to recombinant murine tumor necrosis factor (TNF) neutralizes guinea pig
      TNF.
AB  - Cotton dust has been found to cause acute pulmonary inflammation and fever in
      humans and in a guinea pig model of byssinosis. Following 3 h inhalation of
      cotton dust particles, guinea pig macrophages were found to release ex vivo a
      factor(s) toxic to WEHI fibrosarcoma cells. The cytotoxic factor(s) was also
      present in the bronchoalveolar fluid. We sought to investigate the mechanism of
      the inflammatory response to determine whether the factor was TNF. Antibodies to
      murine TNF were produced by immunizing sets of rabbits using two protocols. All
      animals produced anti-TNF antibodies with titers of 1/1000-1/25,000. Sera from
      one set of animals completely neutralized the cytotoxicity of murine TNF toward
      the WEHI cell line. The antisera neutralized up to 93% of the cytotoxicity of
      guinea pig samples but only 54% of human recombinant TNF. These results identify
      TNF in pulmonary tissues of guinea pigs following exposure to cotton dust.
      Moreover, the studies indicate that rabbit antibodies to murine TNF can be used
      to detect the guinea pig cytokine.

PMID- 1401953
TI  - Rapid DNA typing utilizing immobilized oligonucleotide probe and a nonradioactive
      detection system. Application to HLA-DR typing of the Japanese population.
AB  - We established a rapid and simple method of HLA-DR genotyping, and applied it for
      analysis of the Japanese population. Our method includes rapid preparation of DNA
      samples from buccal mucosa, incorporation of biotin-dATP into DRB genes during
      amplification by the polymerase chain reaction, hybridization with sequence
      specific oligonucleotide (SSO) probes immobilized on nylon membranes via poly
      (dT) tails, and detection of the hybridization signal as chemiluminescence. We
      carried out DR typing of 30 Japanese donors using 20 different immobilized SSO
      probes, and obtained unambiguous typing signals showing perfect correlation with
      their serologic DR types. The genotyping also enabled us to identify several DR
      types unique to the Japanese population, such as DRw12b (DRB1*1202), DRw14c
      (DRB1*1405), and serology blank type, DR'JX6' (DRB1*1403). The method presented
      here would be suitable for routine DR typing in tissue-typing laboratories.

PMID- 1401954
TI  - Isolation of mouse Lyt2- mutant cells using magnetic particles.
AB  - A procedure is described for the selection of mouse Lyt2- mutant cells. The
      procedure is based upon repeated cycles of selection with rat monoclonal
      antibodies to the Lyt2 antigen and magnetic particles coated with goat anti-mouse
      IgG. Stable Lyt2- mutant clones were derived from cells previously mutagenized
      with X rays and, at a lower frequency, also from non-mutagenized cells. The
      procedure can be used to rescue Lyt2- cells when the ratio of Lyt2+:Lyt2- cells
      is 10(4):1.

PMID- 1401955
TI  - A quantitative method for measuring the adherence of group B streptococci to
      murine peritoneal exudate macrophages.
AB  - We have developed a solid phase, direct binding, enzyme-linked immunosorbent
      assay (ELISA) to detect and quantify the adherence of group B streptococci to
      murine macrophages. The assay correlated well with direct microscopic
      quantification of adherence. As few as 3.8 x 10(4) bacteria/assay well or less
      than one bacterium per macrophage could be detected. This assay is both
      quantitative and selective, and is readily adaptable for multiple sample
      analysis. It provides a valuable alternative to visual detection of bacterial
      adherence.

PMID- 1401956
TI  - Factors influencing HIV-1 banding patterns in miniaturized western blot testing
      of dried blood spot specimens.
AB  - In the HIV Seroprevalence Survey among Childbearing Women (SCBW), antibodies to
      human immunodeficiency virus type 1 are detected using enzyme immunoassays (EIA)
      and Western blot (WB) methods modified to accommodate samples of blood dried on
      special collection paper. Dried blood spot (DBS) eluates positive by EIA are
      tested by one of two WB methods, the miniblot technique using equipment from
      Immunetics Corporation and the PBS Integra assay (pageblot) from Genetic Systems.
      In this report we compared the performance of the two WB methods. The identity
      and position of the viral proteins on the WB were identified using monoclonal
      antibodies and monospecific antisera. The blots differed substantially in their
      composition and concentration of viral glycoproteins. Performance of the WB
      assays with DBS elution buffers from different EIA kits was equivalent except for
      samples eluted in the Abbott buffer, which reduced detection of antibodies to the
      p31, p51, p55, and p66 viral proteins. Case classification of DBS, positive sera,
      dilution curve samples, and seroconversion panels was equivalent by both tests in
      the presence of all elution buffers. Proficiency evaluation panels sent to SCBW
      participating laboratories over a 3-year period were used to note the differences
      between the two WB methods in detection of antibodies to the viral glycoproteins.

PMID- 1401957
TI  - In vitro proliferation and the cytotoxic specificity of a cryopreserved cytotoxic
      T cell clone reacting against human autologous tumor cells.
AB  - Proliferation and functional maintenance of CTL after cell cryopreservation often
      proves to be quite difficult. We developed an improved method for proliferating
      cryopreserved CTL, and for gaining their specific cytotoxic function. T cells
      were cryopreserved at -180 degrees C in RPMI 1640 containing 50% FCS and 10%
      DMSO. The cryopreserved T cells were well recovered by culturing in a medium
      containing the supernatant of primary cultures with TIL and autologous tumor
      cells, in addition to a high concentration (350 U/ml) of rIL-2. Furthermore,
      these cells were proliferated more efficiently when MMC-treated autologous tumor
      cells were used in vitro as a feeder and an antigenic stimulant. However, such a
      high dose IL-2 cultivation resulted in the loss of cytotoxic reactivity of CTL
      clone. In contrast, the withdrawal of rIL-2 from in vitro cultivation for 24 h
      prior to the cytotoxic assays conferred the specificity of cytotoxicity on CTL.
      By these methods, one can obtain a large number of CTL, and pursue the
      physiologic detail of the specific cytotoxic mechanism of CTL against autologous
      human tumor cells.

PMID- 1401958
TI  - High gradient magnetic separation of cells on the basis of expression levels of
      cell surface antigens.
AB  - The possibility of separating cells on the basis of levels of antigen expression
      was explored in a model system using fixed erythrocytes and high gradient
      magnetic separation (HGMS). Fixed human erythrocytes were labelled to varying
      degrees with tetrameric monoclonal antibody complexes specific for both dextran
      and glycophorin A-M. The cells were then mixed and incubated with dextran iron
      particles prior to magnetic separation. The small size of the dextran iron
      particles (less than 0.2 microns) resulted in quantitative magnetic labelling of
      cells as shown using fluoresceinated anti-dextran antibodies and flow cytometry.
      The relationships between the initial percentage of labelled cells, cell
      recovery, non-specific entrapment of unlabelled cells, the purity of the removed
      fraction, the degree of antigen expression and separation conditions (flow rate
      and field strength) were determined and used to establish separation conditions
      that allowed recovery of cells that differ only in the degree of antibody
      labelling.

PMID- 1401959
TI  - Dendritic cells from mouse bone marrow: in vitro differentiation using low doses
      of recombinant granulocyte-macrophage colony-stimulating factor.
AB  - Dendritic cells (DC) are potent stimulator cells that are crucially involved in
      primary T cell responses. Since DC comprise a minor population in lymphoid cell
      suspensions tedious and time consuming procedures are required for their
      preparation. This work outlines an in vitro culture system that promotes the
      differentiation of DC from unfractionated mouse bone marrow (BM) cells in the
      presence of low doses of recombinant granulocyte-macrophage colony-stimulating
      factor (GM-CSF). Unlike co-induced BM-macrophages the outgrowing BM-DC express
      high levels of MHC class II molecules; they are negative for specific and
      nonspecific esterase and are nonphagocytic. A rapid one step purification
      procedure employing immunomagnetic bead selection yielded up to 95% BM-DC
      enriched cell fractions. The bead-selected BM-DC were powerful inducers of the
      allogeneic mixed leukocyte reaction. Thus, our findings demonstrate that low dose
      rGM-CSF-driven in vitro culture of BM cells provides convenient access to
      substantial numbers of DC and will greatly facilitate their further exploration.

PMID- 1401960
TI  - Protein growth factor(s) from C6 glioma cells. A reaction to an article by
      Gomathi et al. (JIM 139 (1991) 101-105)

PMID- 1401961
TI  - Restoring antibody activity of a monoclonal anti-RNP antibody by dissociative
      HPLC. Demonstration of blocking antibody binding sites with antigen released from
      effete hybridoma cells.
AB  - In biomedical research, monoclonal anti-nuclear antibodies have a number of
      advantages over polyclonal antibodies in terms of both specificity and
      reproducibility. However, there are some potential problems in the preparation of
      monoclonal antibodies. A well characterized mouse monoclonal anti
      ribonucleoprotein antibody (anti-RNP antibody, 2.73) known to function in Western
      blotting was found to lose this activity when produced in vitro from long term
      hybridoma cell culture. Whilst it could no longer detect RNP antigen by Western
      blotting, it could still function effectively in affinity purification of RNP
      antigen. Further studies suggested that this was due to blocking of antibody
      binding sites by RNP antigen released from effete hybridoma cells in culture. The
      activity of the antibody in affinity purification was retained because the
      antigen was stripped away by repeated elutions with 6 M urea. HPLC gel filtration
      in the presence of 6 M guanidine was able to restore the antibody activity of the
      protein A purified monoclonal antibody. This finding has important general
      consequences for the preparation of monoclonal antibodies against antigens
      present in hybridoma cell culture media.

PMID- 1401962
TI  - An improved method for the purification of IgG monoclonal antibodies from culture
      supernatants.
AB  - A method for the purification of mouse monoclonal antibodies from hybridoma
      culture supernatants is described. The protocol involves the use of a combination
      of three previously described methods for the concentration and purification of
      monoclonal antibodies. Firstly, hybridomas were grown in a Diacult dialysis
      system (Inter Med Laboratory, Denmark) to yield milligram quantities of
      monoclonal antibody in a culture supernatant. Monoclonal antibodies were then
      purified from the culture supernatant by precipitation with polyethylene glycol
      6000 (PEG 6000) and finally reprecipitated using an ammonium sulphate procedure.
      The PEG 6000 treatment caused a density change in the ammonium sulphate
      immunoglobulin precipitate, and resulted in the formation of a pellicle which
      contained pure mouse monoclonal antibody. The protocol removed contaminating
      bovine serum immunoglobulin as well as other serum and cellular protein from the
      monoclonal antibody preparations.

PMID- 1401963
TI  - Effector-target interactions: saturability, affinity and binding isotherms. A
      study of such interactions in the human NK cell-K562 tumour cell system.
AB  - Effector-target interactions at the cell-to-cell level have been studied. This
      has revealed that saturability, i.e., the existence of a finite number of
      specific receptor sites, applies to both the effector and target cell populations
      and plays a key role in the formation of conjugates. As a result, two maximum
      conjugate frequencies, alpha max and beta max, are recognised for the effector
      and target cell populations, respectively. The dissociation constant of the
      conjugates formed, KD, characterizes effector-target affinity. This constant,
      together with the maximum conjugate frequencies, are the three parameters which
      make it possible to describe the binding process quantitatively. The existence of
      binding isotherms for effector-target interactions has been demonstrated. These
      isotherms contain all the relevant information necessary to interpret
      quantitatively the formation of conjugates. Quantitative procedures to determine
      the three binding parameters are described together with the modifications
      necessary to use Scatchard plots in the analysis of conjugate frequencies in
      these kinds of cell-to-cell interactions. A quantitative study of these
      interactions in the NK-K562 tumour cell system has been performed. For this
      purpose, nine different cell source donors were used to test the model proposed.
      Relationships with related phenomena--CMC and the adhesion process--are also
      discussed.

PMID- 1401964
TI  - Optimization of cytotoxic assay by target cell retention of the fluorescent dye
      carboxyfluorescein diacetate (CFDA) and comparison with conventional 51CR release
      assay.
AB  - This paper describes the comparison between a fluorimetric NK assay based on the
      target cell retention of fluorescent dye carboxyfluorescein diacetate (cFDA) and
      standard 51Cr release assay. The results provide several suggestions to improve
      the cytotoxic assay based on the use of the fluorogenic substrate showing that
      the measurements of cFDA retained by target cells represent a method of
      evaluating cytotoxicity completely comparable to the 51Cr release assay.

PMID- 1401965
TI  - Development of a new technique for recovery of cytokines from inflammatory sites
      in situ.
AB  - We attempted to recover cytokines from nasal mucosal surface following allergen
      challenge. Repeated lavage of nasal mucosa of seven allergic patients was done,
      but we failed to detect IL-1 beta in the lavage samples even in ten-fold
      concentrated materials. Therefore, we developed a new technique to recover
      cytokines using filter strips. Small filter strips were placed on nasal
      turbinates for 10 min at different time points after allergen challenge. The
      strips were air-dried, and stored. For recovery of cytokines individual strips
      were washed with small volumes of Hepes buffer containing 0.3% human serum
      albumin. Eluates were assayed for the presence of IL-1 beta and GM-CSF using
      commercially available ELISA. We were able to detect IL-1 beta and GM-CSF in
      eluates. Both cytokines were consistently detectable in the late phase allergic
      reaction peaking at 5 h. Nasal challenge with saline failed to detect any
      cytokine during the 7 h observation period. In standardization experiments known
      quantities of IL-1 beta and GM-CSF were applied to filter strips and the recovery
      ranged from 67 to 89%. Thus, we developed a simple technique of recovery of
      cytokines from inflammatory mucosa in situ.

PMID- 1401966
TI  - Immunological properties of ribosome-inactivating proteins and a saporin
      immunotoxin.
AB  - Antibodies have been raised in rabbits against plant ribosome-inactivating
      proteins (RIPs) and used to demonstrate cross-reactivity between RIPs from plants
      belonging to the same family, but little or no cross-reactivity between RIPs from
      taxonomically unrelated plants. When an immunotoxin consisting of saporin
      conjugated to bovine IgG was injected into rabbits, the animals formed antibodies
      against both saporin and bovine IgG.

PMID- 1401968
TI  - Probity in medical science.

PMID- 1401967
TI  - Acoustic probe-based ELISA.
AB  - The effects of acoustic microstreaming during incubation steps of a prototypical
      three-step ELISA were studied. Acoustic microstreaming, an orderly mixing of
      microwell contents induced by linear oscillation of immersible acoustic probes,
      was shown to be particularly effective when coupled with locating the solid phase
      on the surface of the probes. Optical densities achieved for acoustic probe-based
      assays were equivalent to those for uninsonated microwell-based assays with only
      20% of the microwell solid phase surface area. Low-level antibody detection was
      significantly improved and antibody incubation times significantly shortened
      without loss of signal. Acoustic probe-based assays can enhance assay and
      laboratory efficiency through testing for multiple analytes in a single sample or
      increasing available binding surface area (by using probe and well surfaces
      simultaneously), and by eliminating quenching. Acoustic probe ELISA methodology
      has significant implications for cost-effective automation.

PMID- 1401969
TI  - Spare parts medicine, medical ethics--its follow-up.

PMID- 1401970
TI  - Human rabies: epidemiological and laboratory studies in 80 cases.
AB  - Epidemiological and laboratory studies were conducted on 80 clinically diagnosed
      human rabies cases. Incidence of rabies was more in adult males (55%) and boys
      (37.5%) than adult females (5%) and girls (2.5%) and more in rural areas (76.2%)
      than urban areas (23.8%). Dogs constituted the main vector of transmission
      (92.5%). Incomplete course of antirabic vaccine had been received by 31% of cases
      and 2.5% of cases had complete course of antirabic vaccine. Among the laboratory
      tests conducted 3.8% of corneal smears and 2.5% of saliva smears were positive by
      fluorescent antibody technique. Rabies virus was isolated from 3.8% of saliva and
      3% of cerebrospinal fluid samples. Rabies neutralising antibody titre ranged from
      1:64 to 1:128 in the serum of patients who were fully vaccinated.

PMID- 1401971
TI  - Surgical manifestations and management of ascariasis in Kashmir.
AB  - Amongst 876 cases suffering from ascariasis 662 cases were managed conservatively
      and 214 cases were treated by surgery. Surgical complications were found to be
      more common in males in the age group of 6-10 years. Principal clinical features
      included pain abdomen (99.54%), constipation (80.25%), vomiting (67.46%),
      abdominal distension (47.03%), palpable worm masses in abdomen (35.50%), visible
      peristalsis (27.63%), worms in vomitus (24.20%) and palpable worm clumps on
      rectal examination (20.09%). Principal clinical diagnosis were worm colics
      (48.74%), sub-acute intestinal obstruction (27.74%), acute intestinal obstruction
      (11.42%) and acute intestinal obstruction with strangulation (5.71%); rest of the
      cases included worm cholecystitis (2.63%), obstructive jaundice (1.71%), bile
      peritonitis (0.91%), intestinal perforation (0.68%) and acute appendicitis
      (0.46%). Surgical procedures performed were milking of worms (34.12%), resection
      anastomosis of small intestine (23.36%), enterotomy with removal of worms
      (16.36%), cholecystectomy with T-tube drainage (12.15%), cholecystectomy (8.41%),
      appendectomy (1.87%), resection anastomosis with excision of Meckel's
      diverticulum (1.40%), repair of intestinal perforation with peritoneal toilet
      (1.40%) and cholecystectomy with choledochoduodenostomy (0.93%). In surgically
      managed patients 35 cases died of septicaemia and in conservatively managed cases
      3 died of encephalitis with an overall mortality of 4.34%.

PMID- 1401972
TI  - Rubella infection: a cause of foetal wastage.
AB  - A study was conducted on 180 women with 2 or more obstetric losses totalling 410
      foetal wastages. Control cases included 100 women without obstetric losses.
      Significant titre of immunoglobulin M against rubella was found in 17.77%
      patients with 2 or more obstetric losses in contrast to 9% of control patients (p
      less than 0.005). Significant titre of immunoglobulin M was observed in cases of
      abortions (5.75%), preterm deliveries (12.67%), macerated stillbirths (8.19%),
      fresh stillbirths (8.69%) and neonatal deaths (8.34%).

PMID- 1401973
TI  - Clinically malignant scalp and underlying bone tumours diagnosed by aspiration
      cytology: a study of 121 cases.
AB  - Fine needle aspiration biopsy cytology was employed in 121 cases of clinically
      malignant scalp and underlying bone tumours from July 1984 to March 1991. The age
      of the patients ranged from 2 to 76 years. There were 48 benign cases and 73
      malignant lesions. The cytological findings correlated with histopathological
      analysis except in 5 cases in benign tumours (diagnostic accuracy being 89.6%)
      and in 5 cases in malignant tumours (diagnostic accuracy being 93.2%). The
      clinical history, the radiological parameters and the cytological analysis helped
      to avoid false positive report. No complication was encountered in this
      procedure.

PMID- 1401975
TI  - Cervical spine injury: how easy to miss!
AB  - Acute injuries of the cervical spine are not uncommonly missed on the initial
      examination. In a study of 48 patients of acute injury of the cervical spine, the
      diagnosis was missed initially in 8 patients. The common reasons for missed
      diagnosis had been, head injury in 3 patients, polytrauma in 2, inadequate or
      improper radiologic examination in 2 and erroneous diagnosis in one case.
      Neurologic status was worsened in one patient because of delayed diagnosis.

PMID- 1401974
TI  - Morphological changes in diseased gall bladder: a study of 415 cholecystectomies
      at Aligarh.
AB  - Morphological changes of gall bladder were studied in 415 cholecystectomy
      specimens. There was a preponderance of females (male to female ratio--1:6.5).
      The mean age of the cases was 43.6 years. Most of the cases (63.4%) were in the
      4th and 5th decades of life. The average duration of illness was 2.8 years.
      Associated cholelithiasis was present in 85.3% cases. Gall-stones were of mixed
      variety in 78.2% cases, cholesterol type in 15.3% cases and both types were
      present in 6.5% cases. Chronic cholecystitis was the main histological diagnosis
      (50.8%). Other lesions observed were adenomyomatosis (8.2%), adenomatous
      hyperplasia (10.1%), granulomatous cholecystitis (4.1%), cholesterosis (2.7%),
      acute cholecystitis (4.1%), acute on chronic infection (10.8%), sub-acute
      cholecystitis (2.4%) and carcinoma gall bladder (6.8%). The frequency of
      Rokitansky-Aschoff's sinuses was closely related with the degree of inflammatory
      response. In 13 (6.2%) cases the diagnosis of chronic follicular cholecystitis
      was made. All the cases of cholesterosis were multiparous females and of younger
      age. Of the malignant lesions, adenocarcinoma was the commonest (96.4%).

PMID- 1401976
TI  - Extraneural cryptococcosis.

PMID- 1401977
TI  - Elephantiasis neuromatosa: a clinicopathologic study of four cases.

PMID- 1401978
TI  - Haematometra and endometriosis following accidental transection at internal Os.

PMID- 1401979
TI  - Caroli's disease complicated with carcinoma in situ.

PMID- 1401980
TI  - Role of antisecretory drugs in the treatment of acute diarrhoea.

PMID- 1401981
TI  - Reservations in medical education and jobs.

PMID- 1401982
TI  - Reservations in medical education and jobs.

PMID- 1401983
TI  - Reservations in medical education and jobs.

PMID- 1401984
TI  - Reservations in medical education and jobs.

PMID- 1401985
TI  - Reservations in medical education and jobs.

PMID- 1401986
TI  - Reservations in medical education and jobs.

PMID- 1401987
TI  - Reservations in medical education and jobs.

PMID- 1401988
TI  - Processing of structural polypeptides of infectious flacherie virus of the
      silkworm, Bombyx mori: VP1 and VP4 are derived from VP0.
AB  - Infectious flacherie virus of the silkworm, Bombyx mori, contains five major
      polypeptides termed VP0, VP1, VP2, VP3, and VP4 in the order of descending
      molecular weight. Immunoblot analysis with specific antisera against each of
      these structural polypeptides showed that antisera against VP1 and VP4
      unequivocally reacted with VP0 as well as their homologous structural
      polypeptides. Limited proteolysis of VP0 and VP1 by Staphylococcus aureus V8
      protease gave several common polypeptide fragments. Amino acid sequence analysis
      showed that VP0 and VP4 shared a common NH2-terminal amino acid sequence. These
      results indicate that VP1 and VP4 are generated from VP0 and that VP4 occupies
      the NH2-terminal portion of VP0.

PMID- 1401989
TI  - Relationship of hemolymph phenol oxidase and mosquito age in Aedes aegypti.
AB  - Monophenol oxidase (MPO) and diphenol oxidase (DPO) activity in hemocytes and
      cell-free plasma perfused from 7-, 14-, 21-, and 28-day-old Aedes aegypti
      mosquitoes were compared. A progressive decrease of enzyme activity was detected
      as mosquito age increased, and this decrease was significant in both hemocytes
      and cell-free plasma when mosquitoes were 28 days old as compared with that found
      in 7-day-old mosquitoes. There was no significant difference in total hemolymph
      protein as mosquito age increased. Although this decreased MPO and DPO activity
      might be partially responsible for the reduced immune response against filarial
      worms previously reported for older mosquitoes, other factors undoubtedly play a
      significant role.

PMID- 1401990
TI  - Effect of azadirachtin on the development of Trypanosoma cruzi in different
      species of triatomine insect vectors: long-term and comparative studies.
AB  - Studies were carried out on the effects of azadirachtin on the course of
      Trypanosoma cruzi infection in the gut of different triatomine vector species. In
      Rhodinus prolixus the development of T. cruzi clone Dm28c decreased in a dose
      dependent manner, and the ED50 of this inhibitory effect was 0.25 microgram
      azadirachtin/ml bloodmeal. Using this insect, we conducted a long-term experiment
      which showed that azadirachtin (1.0 microgram/ml bloodmeal) completely blocks the
      development of T. cruzi even 120 days after treatment with the drug, and after
      four infectant meals. Similarly, the elimination of T. cruzi in feces and urine
      was also completely blocked over a period of 50 days after infection in insects
      treated with azadirachtin. Fifth-instar larvae of R. prolixus, Triatoma
      infestans, and Dipetalogaster maximus, infected with different clone/strains of
      T. cruzi, displayed drastic inhibition of trypanosome development when treated
      with azadirachtin. The discussion of these results focuses on the possibility
      that azadirachtin may act directly on gut physiology and/or indirectly through
      the neurosecretory system.

PMID- 1401991
TI  - Larvicidal effects of Penicillium citrinum spores and extracts upon Aedes
      aegypti.

PMID- 1401992
TI  - Internalization of Ia molecules into Birbeck granule-like structures in murine
      dendritic cells.
AB  - Dendritic cells isolated from the draining lymph nodes of mice sensitized
      epicutaneously with hapten are potent antigen-presenting cells and contain
      Birbeck granules and cored tubules characteristic of antigen-activated epidermal
      Langerhans cells. We used immunogold labeling and transmission electron
      microscopy to follow the internalization of Ia molecules in these antigen
      presenting cells. We found that Ia molecules were internalized into Birbeck
      granule-like structures in the antigen-activated dendritic cells. Computer
      reconstruction of serial sections of the dendritic cells demonstrated that these
      structures span the cytoplasm from the cell membrane to the nuclear membrane and
      are associated with lysosomes. The internalization of Ia molecules into these
      structures supports the hypothesis that the Birbeck granule-like structures are
      derived from the cell membrane and are involved in the antigen
      processing/presenting function of the dendritic cells.

PMID- 1401993
TI  - Identification and characterization of a cell surface proteoglycan on
      keratinocytes.
AB  - Proteoglycans fill the intercellular space between keratinocytes but their
      structure and function are not well understood. We have identified and partially
      characterized one intercellular proteoglycan on human keratinocytes, for which we
      propose the name epican (epidermal intercellular proteoglycan). Monoclonal
      antibodies (MoAb) were generated from a mixture of keratinocyte proteoglycans.
      One, designated MoAb17, identified the core protein of an intercellular
      proteoglycan that had an apparent mobility of greater than 250 kDa on Western
      blots. The core protein itself had an apparent mobility of 180 kDa following
      deglycosylation with trifluoromethanesulfonic acid. Enzymatic deglycosylation
      revealed that most core protein molecules were substituted with heparan sulfate
      but that some carried chondroitin sulfate instead. Smaller forms of the core
      protein were more abundant in tissue-culture medium than in cell extracts. This
      proteoglycan was localized by immunofluorescence to the intercellular space of
      the epidermis and the surface of keratinocytes in vitro, particularly at cell
      cell contacts. MoAb17 did not react with protoglycans extracted from other skin
      cells, nor did it bind to basement membranes or connective tissue. Comparison of
      Western immunoblots using MoAb17 and antibodies to core proteins of other
      proteoglycans suggested that epican is not related to syndecan but is a member of
      the CD44 family.

PMID- 1401994
TI  - Topography of proteoglycan and glycosaminoglycan free chain expression in 3T3
      fibroblasts and human keratinocytes.
AB  - Synthesis of heparan sulfate-free chains by human keratinocytes is upregulated
      during terminal differentiation. The cellular location of this product class and
      the significance of the differentiation effect are unknown. Differential plasma
      membrane shearing with cationized colloidal silica was used to evaluate the
      compartmentalization of the heparan and chondroitin sulfate free chains and their
      respective proteoglycans in 3T3 fibroblasts and human keratinocytes. The method
      exploits the topologic segregation of plasma membranes of adherent cells into
      ventral, dorsal, and intracellular domains and the selective binding of the
      silica to the dorsal membranes, which by shearing can be separated from ventral
      membranes adherent to the substratum. Analysis of membrane preparations from
      sheared cells that had been prelabeled with [35S]-sulfate revealed the
      proteoglycans to be predominantly ventral, at which location a matrix binding
      function could be accommodated. Proteoglycans were also recovered from dorsal and
      intracellular membranes, suggesting active trafficking between intra- and extra
      cellular sites. In contrast, the major fraction of heparan and chondroitin
      sulfate free chains was either cytosolic or associated with intracellular
      membranes, with the remaining approximately 20% segregated to dorsal and ventral
      membranes. These results suggest different cellular functions for the
      proteoglycans and glycosaminoglycan free chains. The partial localization of the
      free chains to peripheral membranes is compatible with our prior hypothesis that
      they arise by processing of precursor proteoglycans on cell surfaces. Following
      this origin, the free glycosaminoglycan polymers could be available to bind
      ligands such as cytokines prior to transport to intracellular sites of action.

PMID- 1401995
TI  - Syndecan-1, a cell-surface proteoglycan, changes in size and abundance when
      keratinocytes stratify.
AB  - In epidermis, keratinocytes in the basal cell layer differentiate, lose their
      attachment to the underlying extracellular matrix, and form extensive
      intercellular adhesions as they stratify. The alterations in cell-matrix and cell
      cell adhesion required for keratinocyte stratification result from changes in the
      expression of numerous adhesion molecules. Syndecan-1, a member of a family of
      cell-surface proteoglycans, is known to bind cells to interstitial matrix.
      Syndecan-1 localizes to specific layers of mouse epidermal keratinocytes; its
      expression is modest in the basal layer, heavy in the suprabasal layers, but
      absent from the most superficial, terminally differentiated layers. This layer
      specific difference suggests that syndecan-1 expression changes with keratinocyte
      differentiation. To assess this hypothesis, syndecan-1 expression was evaluated
      before and after calcium-induced stratification and differentiation. Cells
      growing as an unstratified monolayer express a higher molecular mass form of
      syndecan-1 than do stratified cells (modal relative mass of 160 kD versus 110
      kD). This structural difference is due to larger and more heparan sulfate chains
      on syndecan-1 from monolayer cells. In addition, the amount of cell-surface
      syndecan-1 changes with stratification; stratified cultures show approximately
      2.5 times more syndecan-1 per cell than do unstratified cultures, but do not
      significantly change the level of syndecan-1-specific mRNA. Thus, the structure
      and amount of syndecan-1 may be regulated to meet the changing adhesive
      requirements of stratifying keratinocytes.

PMID- 1401996
TI  - Clinical, laboratory, and histopathologic indicators of the development of
      progressive acute graft-versus-host disease.
AB  - Graft-versus-host disease (GvHD) is the major cause of morbidity and mortality
      following bone marrow transplantation (BMT). The goal of this study of 69
      cyclosporin-treated, allogeneic BMT patients was to identify early clinical,
      laboratory, or histopathologic indicators of the development of progressive,
      fatal GvHD. Peak values within 100 d of allogeneic BMT for total bilirubin, stool
      volume in a day, clinical stage of cutaneous GvHD (based on extent of rash), and
      overall clinical stage of GvHD (based on a combination of graft-versus-host
      reactions in the skin, liver, and gastrointestinal tract) were most useful (p
      less than 0.05, by logistic regression) in identifying those patients with
      clinically progressive and fatal GvHD. Peak values for each of these parameters
      were reached an average of 40 d or less after BMT. Each unit increase in peak
      clinical stage of rash (e.g., stage 2 versus stage 3) was associated with an odds
      ratio incremental risk of 5.8 for clinical progression of GvHD, and each tenfold
      increase in peak total bilirubin (e.g., 2 mg/dl versus 20 mg/dl) or stool output
      in a day (e.g., 100 cm3/d versus 1000 cm3/d) was associated with an incremental
      risk of 8.4 and 10.6, respectively, for a fatal outcome from GvHD. Number of
      exocytosed lymphocytes and dyskeratotic epidermal keratinocytes (DEK) per linear
      millimeter of epidermis, the presence of follicular involvement, and the degree
      of dermal perivascular lymphocytic infiltration in 121 skin biopsy specimens were
      not associated with the development of progressive or fatal GvHD. Pretransplant
      total body irradiation was associated (p = 0.03, by Mann-Whitney U testing) with
      an increased number of DEK in skin biopsy specimens taken less than 20 d after
      BMT. This study demonstrates that monitoring of total bilirubin, stool output,
      extent of rash, and overall clinical stage of GvHD is most useful during the
      first 40 d after BMT in formulating the prognosis of early acute GvHD in
      allogeneic BMT patients receiving cyclosporin.

PMID- 1401997
TI  - Enhanced IL-4 production and IL-4 receptor expression in atopic dermatitis and
      their modulation by interferon-gamma.
AB  - The in vivo and in vitro immunomodulatory effects of interferon gamma (IFN-gamma)
      treatment on peripheral blood mononuclear cells (PBMC) from patients with atopic
      dermatitis (AD) and elevated IgE levels were studied. As part of a double-blind
      placebo-controlled clinical trial, 14 AD patients were treated with IFN-gamma (n
      = 7) or saline (n = 7) for 12 weeks. To assess the in vivo effects of IFN-gamma
      treatment on interleukin (IL)-4-dependent lymphocyte function, we assessed the
      proliferation of AD PBMC in response to IL-4. Prior to IFN-gamma treatment, AD
      PBMC had proportionately decreased proliferative responses to IL-4 when compared
      to IL-2. After 12 weeks of in vivo treatment with IFN-gamma, there was an
      increase of IL-4- but not IL-2-induced lymphocyte proliferation in seven of eight
      AD patients. To further study the immunologic basis of these observations, we
      studied the expression of IL-4 receptor (IL-4R) mRNA and the production of IL-4
      by PBMC from AD patients. PBMC from AD patients expressed higher levels of IL-4R
      mRNA and produced significantly higher amounts of IL-4 than normal controls (p
      less than 0.05). More importantly, the in vitro addition of IFN-gamma caused
      significant reduction in both IL-4R and mRNA expression and IL-4 production of
      PBMC from AD and non-atopic controls. These data indicate that AD is
      characterized by an in vivo overstimulation of the IL-4-IL-4R pathway. The poor
      proliferative responses of untreated AD PBMC to exogenous IL-4 may be due to
      increased levels of endogenous IL-4 production with constant occupancy on the IL
      4R. Furthermore, in vivo and in vitro treatment with IFN-gamma down-regulates
      this pathway.

PMID- 1401998
TI  - Transforming growth factor-beta up-regulates the expression of the genes for beta
      4 integrin and bullous pemphigoid antigens (BPAG1 and BPAG2) in normal and
      transformed human keratinocytes.
AB  - Three distinct proteins, namely, beta 4 integrins, and the 230-kDa (BPAG1) and
      180-kDa (BPAG2) bullous and pemphigoid antigens, have been shown to co-localize
      with hemidesmosomes at the dermal-epidermal basement membrane zone. In this
      study, we examined the expression of the corresponding genes in cultures of
      normal and transformed human epidermal keratinocytes. The expression of these
      genes was detected by Northern and in situ hybridizations, and the expression of
      beta 4 integrins was also demonstrated by indirect immunofluorescence. The
      results indicated clearly detectable expression of all three genes in normal
      keratinocytes, whereas extremely low or undetectable levels of expression were
      noted in two transformed cell lines. Addition of TGF-beta 1 or TGF-beta 2 (10
      ng/ml) up-regulated mRNA levels for all three proteins (up to 4.6 times). The
      increase by TGF-beta 1 was particularly striking in keratinocyte cultures
      incubated in the presence of low (0.15 mM) Ca++, and somewhat less pronounced in
      the presence of high (1.2 mM) Ca++. The increase in beta 4 integrin synthesis was
      also documented by enhanced immunosignal of the corresponding epitopes. These
      results indicate that the three hemidesmosomal genes studied here are all
      responsive to TGF-beta. These observations, together with previous data on the
      effects of TGF-beta on other components of the skin, suggest that this cytokine
      may play a role in the development and repair of the cutaneous basement membrane
      zone.

PMID- 1401999
TI  - Characterization, expression, and immunohistochemical localization of 3 beta
      hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin.
AB  - Three beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD)
      catalyses an obligatory step in the biosynthesis of all classes of hormonal
      steroids, namely, the oxidation/isomerization of 3 beta-hydroxy-5-ene steroids
      into the corresponding 3-keto-4-ene steroids in gonadal as well as in peripheral
      tissues. Because humans are unique with some primates in having adrenals that
      secrete large amounts of the steroid precursors dehydropiandrosterone (DHEA) and
      its sulfate (DHEA-S) and its exceptionally large volume makes the skin an
      important site of steroid biosynthesis, we have isolated and characterized cDNA
      clones encoding 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase
      from a human skin lambda gt11 library. The longest clone obtained contains the
      entire coding sequence for type I 3 beta-HSD (372 amino acids) as well as an
      additional 131 nucleotides in the 5'-untranslated region. The insert of 1647 bp
      containing the entire coding region has been inserted in a pCMV expression vector
      and transfected into human cervical carcinoma cells (HeLa). The expressed enzyme
      efficiently catalyzes the transformation of pregnenolone, DHEA, and
      dihydrotestosterone into progesterone, 4-androstenedione, and 5 alpha-androstane
      3 beta, 17 beta-diol, respectively. Using the enzyme expressed in HeLa cells, we
      have shown cyproterone acetate, a progestin used in the treatment of acne and
      hirsutism, as well as norgestrel and norethindrone, two steroids widely used as
      oral contraceptives, to be relatively potent inhibitors, with Ki values of 0.38
      microM, 1.3 microM, and 1.2 microM, respectively. Immunohistochemical
      localization of 3 beta-HSD, illustrated by using an antibody raised against human
      placental 3 beta-HSD, shows that the enzyme is localized in sebaceous glands.

PMID- 1402000
TI  - Epidermal keratinocyte self-renewal is dependent upon dermal integrity.
AB  - The epidermis is a major site of self-renewal in which there is constant
      replacement by cell division in the basal layers of cells lost by desquamation in
      the superficial layers. Such a tissue is therefore likely to contain stem cells
      and in this study we have examined the role of the dermis in the maintenance of
      epidermal self-renewal. We have developed a mouse model to address the question
      of whether the maintenance of epidermal self-renewal is dependent, as in the
      hemopoietic system, upon a heterologous cell type. Intact epidermis separated
      from dermis at the dermo-epidermal junction or epidermis derived from
      disaggregated epidermal cells, can reconstitute a stratified squamous epithelium
      when grafted onto the lumbo-dermal fascia of the mouse or onto an experimentally
      induced granulation tissue bed. However, we have shown that, after grafting, the
      clonogenic capacity of the keratinocytes declines sharply and the colonies that
      are produced are incapable of self-renewal in vitro. Although initially
      hyperplastic, these epidermal grafts assume an atrophic appearance after 40-70 d
      and this may be related to the loss of self-renewal observed in vitro. With both
      experimental murine grafts and clinical grafts the failure of keratinocytes to
      self-renew can be alleviated, partially, by the presence of the dermis in full
      thickness or split-thickness grafts, which implies that the dermis has a
      functional role in epidermal stem cell maintenance. The relevance of these
      observations to the clinical experience with cultured autologous keratinocyte
      sheets as wound dressings to patients is discussed.

PMID- 1402001
TI  - Percutaneous absorption of flurbiprofen in the hairless rat measured in vivo
      using 19F magnetic resonance spectroscopy.
AB  - The objective of this investigation was to develop a new methodology using 19F
      magnetic resonance spectroscopy (MRS) to measure the in vivo percutaneous
      absorption of flurbiprofen through hairless rat skin. A 2% W/V flurbiprofen gel
      (Klucel HF, hydroxypropyl cellulose 1.5% to 2% W/V) containing isopropyl alcohol,
      water, and propylene glycol (55:35:10 v/v/v) was prepared. A 2-mg dose (100 mg of
      gel) was applied to the skin of the lower back of an anesthetized hairless rat,
      contained with a rubber o-ring, and occluded with a lexan plastic cover slip. The
      animal was placed on an MR surface coil (3.5-cm diameter tuned to 19F) and
      measurements taken continuously over approximately 3 h in 10-min intervals with a
      2-tesla GE CSI nuclear magnetic resonance (NMR) spectrometer. One measures the
      disappearance of MR signal intensity per interval, which directly relates to the
      percent of drug disappearance over time, which in turn was converted to a flux
      value. The flux of flurbiprofen in vivo was found to be 95 +/- 22
      micrograms/cm2/h. This is approximately four times greater than the flux of
      flurbiprofen through excised human skin reported by Akhter and Barry (22 +/- 14
      micrograms/cm2/h). This new in vivo method measures drug disappearance and can be
      readily transferred to man. This method may be adapted to study other fluorine
      compounds or other nuclei with magnetic properties. It avoids exposure of a
      patient or animal to the radiation used in x-ray fluorescence methods or to 14C-
      or 3H-radiolabeled drugs.

PMID- 1402003
TI  - Differential effects of structurally unrelated chemical irritants on the density
      of proliferating keratinocytes in 48 h patch test reactions.
AB  - Alterations in the proliferative capacity of human epidermis following topical
      exposure to structurally unrelated chemical irritants were investigated, with the
      aim of improving our understanding of the cellular changes that take place during
      the development of irritant contact dermatitis (ICD). Healthy volunteers were
      patch tested for 48 h with the following six irritants and their appropriate
      vehicle and occlusion controls: 5% sodium lauryl sulphate (SLS), 0.5%
      benzalkonium chloride, 80% nonanoic acid (NAA), 0.02% dithranol, 0.8% croton oil,
      and 100% propylene glycol (PG). After the degree of inflammation induced was
      visually graded, biopsy samples were removed and the dividing keratinocytes were
      identified immunocytochemically by using the monoclonal antibody Ki-67, with
      quantification being performed on the basis of the number of positive cells/100
      basal keratinocytes. Statistically significant increases in the density of
      proliferating cells occurred in the reactions to SLS, NAA, and PG, whereas, in
      contrast, dithranol caused a marked decrease in the number of dividing
      keratinocytes. Overall, the density of proliferating keratinocytes did not show a
      linear relationship with the visually assessed intensity of inflammation,
      indicating that the changes observed were related to the chemical nature of the
      individual irritants and their specific biochemical interactions with the
      keratinocytes, rather than being the consequence of a generalized inflammatory
      response. Differential release of epidermal cytokines and mediators by the six
      irritants may account for these varying states of keratinocyte proliferation.
      Application of the Spearman rank coefficient of correlation revealed that the
      changes in mitotic activity of keratinocytes were unrelated either to the total
      density of leukocytes infiltrating the epidermis and dermis, or to the individual
      densities of the major phenotypic classes of inflammatory cells present. This
      makes it unlikely that the localized release of cytokines by infiltrating
      leukocytes is, by itself, the primary factor in the alteration in epidermal cell
      kinetics seen in ICD. Our results provide a further demonstration of the diverse
      actions of different chemical irritants on human skin and emphasize the need to
      regard ICD as a heterogeneous disorder.

PMID- 1402002
TI  - Ultraviolet A irradiation stimulates collagenase production in cultured human
      fibroblasts.
AB  - This study was designed to investigate the biochemical mechanisms responsible for
      the connective tissue changes seen in actinically damaged skin, which is
      characterized histologically by diminution and ultrastructural alterations of
      collagen fibrils and deposition of elastotic material in the papillary dermis. We
      hypothesized that ultraviolet light could stimulate synthesis of interstitial
      collagenase in the skin, resulting in collagen degradation. Monolayer cultures of
      human fibroblasts or keratinocytes were irradiated with ultraviolet A (UVA) or
      ultraviolet B (UVB) radiation and interstitial collagenase or its inhibitor, TIMP
      (tissue inhibitor of metalloproteinases) assessed in the conditioned medium with
      Western immunoblots 24 h after irradiation. Northern blot analysis of the
      irradiated fibroblasts with a cDNA probe representing collagenase was also
      performed. Cell viability was greater than 90% with all doses of UV radiation
      studied. A dose-related increase in immunoreactive collagenase was detected in
      the medium of fibroblasts irradiated with 0-10 J/cm2 of UVA radiation as well as
      a parallel increase in the collagenase mRNA in the irradiated cells. UVA
      radiation stimulated collagenase synthesis in both neonatal and adult
      fibroblasts. TIMP production in UVA-irradiated fibroblasts increased to a lesser
      degree than did collagenase and its increase did not parallel the increase in
      collagenase. UVB (0-100 mJ/cm2) did not stimulate collagenase production by
      fibroblasts. In contrast to the stimulation of collagenase production by
      fibroblasts, a slight decrease in immunoreactive collagenase was seen in UVA
      irradiated keratinocytes. These data suggest that direct stimulation of
      collagenase synthesis by human skin fibroblasts by UVA radiation may contribute
      to the connective tissue damage induced by ultraviolet radiation leading to
      photoaging.

PMID- 1402004
TI  - Cultured human melanocytes from black and white donors have different sunlight
      and ultraviolet A radiation sensitivities.
AB  - Short-term and long-term survival of cultured neonatal foreskin melanocytes from
      black and white individuals were assessed following a single exposure to
      simulated sunlight or ultraviolet A (UVA) radiation. Melanocytes from black
      individuals contained significantly more melanin than melanocytes from white
      individuals (p less than 0.05). Black and white melanocytes had similar survival
      profiles following simulated sunlight exposure, whereas black melanocytes were
      significantly more resistant to UVA cytotoxicity than melanocytes from white
      subjects (p less than 0.05) at UVA doses above 15 J/cm2. There was no difference
      in unscheduled DNA synthesis in the black or white melanocytes following
      simulated sunlight exposure and no unscheduled DNA synthesis was measurable
      following melanocyte exposure to UVA radiation. Low-dose UVA (1 or 5 J/cm2) was
      mitogenic to both black and white melanocytes. By analysis of co-variance, the
      melanin content of melanocytes of black and white subjects was significantly (p
      less than 0.05) associated with susceptibility to UVA killing; melanocytes with
      high melanin content had high resistance to UVA cytotoxicity and those with low
      melanin content had low resistance to UVA cytotoxicity. From these data we
      suggest that the higher melanin content of melanocytes of black subjects confers
      increased resistance to UVA damage. This is likely to be of importance in
      epidermal photodamage.

PMID- 1402005
TI  - Skin color measurements in terms of CIELAB color space values.
AB  - The principles of color measurement established by the Commission International
      d'Eclairage have been applied to skin and the results expressed in terms of color
      space L*, hue angle, and chroma values. The distribution of these values for the
      ventral forearm skin of a sample of healthy volunteers is presented. The skin
      color characteristics of a European subgroup is summarized and briefly compared
      with others. Color differences between individuals were identified in terms of
      one, two, or all three color-space parameters. Because the method is quantitative
      and the principles internationally recognized, these color-space parameters are
      proposed for the unambiguous communication of skin-color information that relates
      directly to visual observations of clinical importance or scientific interest.

PMID- 1402006
TI  - Allergic contact dermatitis releases soluble factors that stimulate melanogenesis
      through activation of protein kinase C-related signal-transduction pathway.
AB  - Phenylazo-naphthol (PAN) allergy induces visibly well-defined and late-appearing
      hyperpigmentation of brownish yellow guinea pig skin in clear contrast to
      dinitrochlorobenzene (DNCB) allergy, which has very low incidence of
      hyperpigmentation. Skin extract from PAN allergy at 20-29 d post-challenge
      exhibited marked melanogenic stimulatory effects (3H2O release and 14C-thiouracil
      incorporation) when added to cultured guinea pig melanocytes. The time course in
      the appearance of melanogenic factor was definitely consistent with the induction
      pattern of visible pigmentation. By contrast, the addition of DNCB-challenged
      skin extract demonstrated no significant stimulating effect on melanogenesis in
      either assay system on any of the post-challenge days tested. Assay of
      intracellular inositol 1,4,5-trisphosphate formed through incubation with the
      melanocytes demonstrated that the PAN-allergy skin extract at day 28, which
      contains definite melanogenic factors, stimulated the formation of inositol 1,4,5
      trisphosphate that occurs around 50 seconds in contrast to no or little increase
      with extracts obtained at days 0 and 1 post-challenge. Gel chromatographic
      analysis revealed that the PAN-allergy skin extract at day 28 contained a newly
      generated melanogenic fraction with a molecular weight of approximately 9000 Da
      which was also capable of stimulating DNA synthesis and activating the signal
      transduction process (inositol trisphosphate formation) when added to guinea pig
      melanocytes. Both stimulations of melanogenesis and DNA synthesis by the 9000 Da
      fraction were completely abolished by the prior and simultaneous addition of
      protein kinase C (PKC) inhibitor (H-7) or its down-regulatory agent, phorbol
      12,13-dibutyrate (PdBu). Taken together, these results suggest that PAN allergy
      provides a new mechanism of hypermelanization in which endogenous factors
      synthesized within skin induce the activation of signal-transduction pathways
      such as phosphoinositide turnover through ligands-receptor binding, resulting in
      the stimulation of melanocytes possibly through the activation of PKC.

PMID- 1402007
TI  - Expression of integrin alpha 6 beta 4 in junctional epidermolysis bullosa.
AB  - The integrin alpha 6 beta 4 is a member of the integrin family of adhesion
      receptors. The integrin alpha 6 beta 4 is preferentially expressed in stratified
      squamous epithelia, where it is localized in hemidesmosomes. A reduced number of
      rudimentary hemidesmosomes is often found in skin from patients with junctional
      epidermolysis bullosa (JEB). In this study we have investigated the expression of
      alpha 6 beta 4 in skin specimens of patients with junctional (one non-lethal, two
      lethal) and dystrophic (two) epidermolysis bullosa, using immunofluorescent (IF)
      staining with five different monoclonal antibodies against the alpha 6 and beta 4
      subunits. The intensity of IF staining of the integrin alpha 6 beta 4 and bullous
      pemphigoid antigen (BPA) was unreduced along the epidermal basement membrane zone
      (EBMZ) of all EB patients, compared to that in skin of healthy human controls.
      However, in the skin of two patients with lethal (Herlitz) JEB, who did not
      express GB3, IF staining of integrin alpha 6 beta 4 and BPA showed a "stitchy"
      discontinuous linear pattern along the EBMZ with interruptions at the borders of
      adjoining basal keratinocytes. The same results were obtained by immunoelectron
      microscopy. They corresponded with freeze-induced partial cell detachment from
      the basement membrane at the ultimate baso-lateral edge of the basal
      keratinocytes in lethal JEB skin. The basal lamellipodia at that location almost
      completely lacked tonofilaments and hemidesmosomes. Furthermore, in JEB there was
      a split between the intra- and extracellular epitopes of the integrin alpha 6
      beta 4 receptor, whereas the integrin remains intact in salt-split skin. This
      suggests that the defect is in alpha 6 beta 4 itself or perhaps its ligand.

PMID- 1402008
TI  - Expression of 92-kDa type IV collagenase mRNA by eosinophils associated with
      basal cell carcinoma.
AB  - Metalloproteinases are thought to be important for tumor invasion and metastasis.
      We used in situ hybridization with 35S-labeled cRNA probes to localize sites of
      expression for 92-kDa type IV collagenase mRNA in sections of nodular basal cell
      carcinoma. Positive signal for 92-kDa type IV collagenase mRNA was detected in
      eosinophilic granulocytes within inflammatory infiltrates surrounding the tumor
      nodules. Eosinophils, however, were not adjacent to tumor cells, suggesting that
      metalloenzyme production by these granulocytes in this disease may be targeted
      more to stromal components than to remodeling or destruction of the basement
      lamina. The identity of the eosinophils was confirmed by cell morphology and
      specific histochemical staining. No resident or other migratory cells were
      positive for enzyme mRNA in these samples. Signal specificity for in situ
      hybridization was shown by a duplication of the results with complementary
      oligomeric probes and by a lack of signal in sections hybridized with a sense RNA
      probe or nonspecific oligomer. No signal for 92-kDa type IV collagenase mRNA was
      detected in circulating eosinophils or in eosinophils associated with Hodgkin's
      lymphoma. These data suggest that eosinophils migrate into the dermis and express
      type IV collagenase in response to basal cell carcinoma and that this process may
      have a role in tumor growth.

PMID- 1402009
TI  - Control of human sebocyte proliferation in vitro by testosterone and 5-alpha
      dihydrotestosterone is dependent on the localization of the sebaceous glands.
AB  - Androgens stimulate the activity of sebaceous glands in vivo. In this study the
      in vitro effect of androgens on the proliferation of cultured human sebocytes
      derived from facial and non-facial skin were assessed. Human sebocytes from
      sebaceous glands isolated from the face and the upper and lower legs of five
      individuals were cultured in vitro with or without testosterone or 5-alpha
      dihydrotestosterone (5 alpha-DHT) at different concentrations (10(-11)-10(-5) M).
      Cell proliferation was assessed in 96-well culture plates using a fluorometric
      assay. Testosterone and 5 alpha-DHT stimulated the proliferation of human facial
      sebocytes in a significant dose-dependent manner. In our system 5 alpha-DHT
      exhibited the strongest effect; on the contrary, the proliferation of non-facial
      sebocytes was inhibited by testosterone, whereas 5 alpha-DHT enhanced their
      growth. The stimulatory effect of 5 alpha-DHT was more prominent on facial than
      on non-facial sebocytes. These results provide first evidence that the effect of
      testosterone and 5 alpha-DHT on the proliferation of cultured human sebocytes may
      depend on the localization of the sebaceous glands at different skin regions.

PMID- 1402010
TI  - Epidermal interleukin 1 alpha functional activity and interleukin 8
      immunoreactivity are increased in patients with cutaneous T-cell lymphoma.

PMID- 1402011
TI  - Prevalence and characteristics of pharyngeal group A beta-hemolytic streptococci
      in US Navy recruits receiving benzathine penicillin prophylaxis.
AB  - US military recruits receive benzathine penicillin prophylaxis because of
      endemicity of group A beta-hemolytic streptococcal (GABHS) infections. GABHS
      prevalence in Navy recruits receiving single-dose benzathine penicillin
      prophylaxis was assessed during spring and fall 1989 by culturing throat
      specimens from randomly selected groups of approximately 230 men before and 2, 4,
      and 7 weeks after prophylaxis and from men with pharyngitis diagnosed at sick
      call. Of 60 GABHS isolates, 75% were serotype M-3. The pharyngitis rate increased
      from 0.18% in the spring to 1.55% in the fall with a concurrent increase in
      serotype M-3 prevalence from 35% to 91%. The GABHS prevalence rate was three- to
      fourfold lower after prophylaxis. There were no cases of acute rheumatic fever
      (ARF) despite predominance of M-3, a rheumatogenic serotype. It was concluded
      that penicillin prophylaxis continues to be effective for control of GABHS
      infections and prevention of ARF in Navy recruits.

PMID- 1402012
TI  - Genetic diversity in T1M1 group A streptococci in relation to clinical outcome of
      infection.
AB  - Genetic diversity was found at high frequency downstream of the emm1 gene among
      T1M1 group A streptococci (GAS) isolated in Scandinavia during a recent epidemic.
      Clonal variation was also seen in the speA and speB genes but at much lower
      frequency; no variation was detected in the speC gene. Erythrogenic toxin A was
      found to be expressed at low levels in all strains; erythrogenic toxins B and C
      were produced in high amounts. All strains were found to harbor the speA, speB,
      and speC genes, regardless of the amount of toxin produced. No correlation was
      found between one specific T1M1 clone and the more serious infections when
      isolates from bacteremic patients (fatalities or survivors), those with
      uncomplicated infections, and healthy carriers were compared. Similar results
      were obtained in a family study in which 3 family members were found to be
      asymptomatic carriers of the same GAS T1M1 clone as in the bacteremic patient,
      defined by genotypic and phenotypic experiments.

PMID- 1402013
TI  - Immunogenicity of Haemophilus influenzae type b conjugate vaccine in allogeneic
      bone marrow recipients.
AB  - A randomized study was conducted in 40 allogeneic marrow recipients to compare
      the immunogenicity of two Haemophilus influenzae type b (Hib) vaccines (either
      the Hib capsular polysaccharide [Hib-CPS] or tetanus toxoid-conjugated Hib-CPS
      [Hib-CPS-T]). A second injection consisted of Hib-CPS-T. Before immunization, 3
      patients had serum antibody levels > 1 microgram/mL. After the first injection,
      the response was better after Hib-CPS-T than after Hib-CPS but lower than in
      normal subjects; a number of patients lacked any IgG antibody response,
      especially after Hib-CPS. Of patients who received two injections of Hib-CPS-T,
      85% achieved an antibody concentration > or = 1 microgram/mL. Hib-CPS-T induced a
      response in IgG2-deficient patients whereas Hib-CPS alone did not. IgG antibodies
      predominantly belonged to the IgG1 subclass. The antibody response was better in
      patients immunized late after graft. This study shows that Hib-CPS-T is more
      immunogenic than Hib-CPS in marrow recipients.

PMID- 1402014
TI  - Evidence that inactivated oral cholera vaccines both prevent and mitigate Vibrio
      cholerae O1 infections in a cholera-endemic area.
AB  - In a randomized, placebo-controlled field trial of B subunit-killed whole cell
      (BS-WC) and killed whole cell only (WC) inactivated oral cholera vaccines in
      rural Bangladesh, active surveillance of selected neighborhoods during the first
      year after vaccination identified 127 Vibrio cholerae O1 infections among 3285
      three-dose recipients. For each vaccine, protective efficacy was greater against
      symptomatic (57%, P < .05 for BS-WC; 58%, P < .05 for WC) than against
      asymptomatic infections (46%, P < .05 for BS-WC; 32%, P = .09 for WC), and
      protection against each grade of infection was demonstrable for both the
      classical and El Tor biotypes. Although vaccine protection against symptomatic
      infections was evident in both young children and older persons, only persons
      vaccinated at age > 5 years were protected against asymptomatic infections. These
      results suggest that the inactivated oral vaccines acted both to protect against
      intestinal colonization by V. cholerae O1 and to interrupt the pathogenic
      sequence of established infections.

PMID- 1402015
TI  - Toxicity in neuronal cells caused by cerebrospinal fluid from pneumococcal and
      gram-negative meningitis.
AB  - To identify neurotoxic factors in meningitis, a neuronal cell line (HN33.1) was
      exposed to cerebrospinal fluid (CSF) obtained from rabbits with pneumococcal
      meningitis or Escherichia coli meningitis or 2 h and 6 h after meningitis was
      induced by proinflammatory bacterial products (pneumococcal cell walls,
      endotoxin). CSF from all types of meningitis induced similar degrees of
      cytotoxicity. When a soluble tumor necrosis factor (TNF) receptor that completely
      blocked TNF-mediated toxicity at 10(-7) M was used, all toxicity in meningitis
      caused by E. coli, endotoxin, or pneumococcal cell wall administration (2 h
      afterwards) was mediated by TNF. In contrast, CSF from animals with meningitis
      caused by live pneumococci or pneumococcal cell wall injection (6 h afterwards)
      retained cytotoxicity in the presence of the TNF receptor. Thus, in established
      pneumococcal meningitis, but not in the other forms of meningitis, TNF is not the
      only component toxic in this neuronal cell line.

PMID- 1402016
TI  - Frequencies of lipopolysaccharide core types among clinical isolates of
      Escherichia coli defined with monoclonal antibodies.
AB  - Mouse monoclonal antibodies (MAbs) specific for the lipopolysaccharide (LPS) core
      types R1, R2, and R3 of Escherichia coli and a cross-reactive MAb that binds to
      the LPS core of almost all E. coli were used in ELISA to determine the frequency
      of cores resembling R1, R2, and R3 in strains of E. coli isolated from clinical
      samples (blood and urine specimens) and from the feces of asymptomatic
      individuals. Of the 180 wild-type isolates, 123 were assigned to R1 core type, 14
      to R2, and 18 to R3. Twenty-five wild-type E. coli isolates could not be assigned
      to a particular core type and may have either an R4 or K12 core or a previously
      unrecognized core type. R1 core type was associated with O types 1, 4, 6, 8, and
      18 and with K1 or K5 capsules. R3 was associated with O15. O75 isolates could be
      of either R1 or R2 core type.

PMID- 1402017
TI  - Characterization of Staphylococcus aureus isolates with decreased susceptibility
      to vancomycin and teicoplanin: isolation and purification of a constitutively
      produced protein associated with decreased susceptibility.
AB  - "Derivative isolates" with 4- to 8-fold and 8- to 16-fold increases in MICs of
      vancomycin and teicoplanin, respectively, were selected from 2 susceptible
      clinical isolates of Staphylococcus aureus by serial incubation in low-level
      vancomycin. A protein of approximately 39 kDa was demonstrable in the cytoplasmic
      fraction and occasionally in the membrane fraction by SDS-PAGE of both
      derivatives. This protein was purified by DEAE chromatography, preparative SDS
      PAGE, and electroelution. Derivative bacteria were larger on transmission
      electron microscopy, had thicker cell walls, and had changes in colony morphology
      on solid media. Further evidence for cell wall reorganization included loss of
      phage and capsular typing, decreased susceptibility to lysostaphin/lysozyme
      killing, and changes in condition for detection of optimal coagulase activity.
      The mechanism of decreased susceptibility to glycopeptide antibiotics among S.
      aureus derivative isolates is uncertain. The production of the approximately 39
      kDa cytoplasmic protein and cell wall reorganization may mediate changed affinity
      of glycopeptide-peptidoglycan binding or impairment of glycopeptide access to its
      cell wall target.

PMID- 1402018
TI  - Potentiation of Helicobacter pylori vacuolating toxin activity by nicotine and
      other weak bases.
AB  - About 50% of Helicobacter pylori isolates produce a vacuolating toxin in vitro,
      which may be an important determinant of virulence. Because ammonium salts
      potentiate H. pylori toxin activity, the effect of other weak bases upon toxin
      activity was determined. Vacuolation of HeLa cells was quantitated using a
      neutral red uptake assay. As expected, ammonium chloride, trimethylamine,
      triethanolamine, and nicotine each induced vacuolation of HeLa cells when tested
      independently. In addition, each of these weak bases potentiated H. pylori
      vacuolating toxin activity, whereas sodium chloride or sodium hydroxide did not.
      Sequential incubation of cells with toxin followed by nicotine resulted in
      potentiation of vacuolation, whereas sequential incubation in the reverse order
      did not lead to potentiation. Monensin inhibited the formation of vacuoles by
      either H. pylori vacuolating toxin or nicotine. The potentiation of H. pylori
      toxin activity by ammonia and nicotine may contribute to gastroduodenal mucosal
      injury associated with this infection.

PMID- 1402019
TI  - Sialylation and human neutrophil killing of group C Neisseria meningitidis.
AB  - This study describes the association of lipooligosaccharide (LOS) and capsule
      sialylation with the survival of 25 serogroup C meningococcal strains in
      phagocytosis assays. Eleven strains isolated from children were of diverse
      protein serotypes or were nontypeable; 14 were serotype 2b:P1.2 and were isolated
      from children during or immediately after a focal epidemic in Texas. Degree of
      endogenous LOS sialylation and amount of sialic acid capsule were associated with
      each other and with susceptibility to killing by neutrophils for the non-2b:P1.2
      strains. The 2b:P1.2 strains as a group had significantly greater survival in the
      presence of neutrophils than did the non-2b:P1.2 strains. The susceptibility of
      these strains to killing by neutrophils was not associated with endogenous LOS
      sialylation or amount of capsule. These data suggest that many virulent strains
      evade neutrophil killing, either by sialylation or another mechanism. Evasion of
      neutrophil killing might enhance a strain's epidemic potential.

PMID- 1402020
TI  - Recombinant interleukin-8 induces changes in cytosolic Ca2+ in human neutrophils.
AB  - Activation of polymorphonuclear leukocytes (PMNL) by most soluble stimulants is
      associated with a marked increase in cytosolic free Ca2+ ([Ca2+]i). Interleukin-8
      (IL-8), a monocyte-derived neutrophil chemotactic factor and potent neutrophil
      activating cytokine, effectively enhanced the resting free [Ca2+]i within human
      PMNL in a dose-dependent manner (maximal effect with 100 ng/mL). The increase in
      [Ca2+]i was substantially (55%) inhibited in the absence of extracellular Ca2+.
      Thus, the increase was due to extra- and intracellular cooperative mobilization
      of Ca2+, as supported by the reduced effect of IL-8 on [Ca2+]i after quenching
      with Mn2+. Granulocyte-macrophage colony-stimulating factor and interferon-gamma
      failed to induce a change in [Ca2+]i, suggesting that they may operate through
      different signal pathways. Pretreatment with Bordetella pertussis toxin largely
      inhibited the IL-8-induced change in [Ca2+]i. Thus, IL-8-induced cooperative
      mobilization of intra- and extracellular Ca2+ leads to a net Ca2+ influx into the
      cytoplasm through a process mediated by a guanosine triphosphate-binding protein.

PMID- 1402021
TI  - Phagolysosomal alkalinization and the bactericidal effect of antibiotics: the
      Coxiella burnetii paradigm.
AB  - Most infections due to intracellular bacteria respond poorly to antibiotic
      treatment. The chemical conditions within the subcellular site of bacteria may
      change antibiotic activity. Coxiella burnetii multiplies within phagolysosomes.
      The antimicrobial activity of antibiotics combined with the lysosomotropic agents
      amantadine (1 microgram/mL), chloroquine (1 microgram/mL), and ammonium chloride
      (1 mg/mL), which alkalinized Coxiella burnetii-containing phagolysosomes from pH
      4.8 to 5.3, 5.7, and 6.8, respectively, was evaluated. Percentages of residual
      viable bacteria (RVB) in cell cultures were significantly reduced after exposure
      to combinations of doxycycline (4 micrograms/mL) with amantadine (RVB = 18.2% +/-
      8.7%, P < .05), chloroquine (RVB = 0.64% +/- 0.38%, P < .01), or ammonium
      chloride (RVB = 0.29% +/- 0.17%, P < .01); the same was seen with pefloxacin (1
      microgram/mL) with chloroquine (RVB = 27.6% +/- 10.8%, P < .05) or ammonium
      chloride (RVB = 3.72% +/- 1.1%, P < .05). Such bactericidal activity correlated
      with increased phagolysosomal pH, as determined by Pearson's correlation
      coefficient, suggesting that phagolysosomal alkalinization is critical for the
      bactericidal effect of antibiotics.

PMID- 1402022
TI  - Identification of a mannoprotein fraction from Candida albicans that enhances
      human polymorphonuclear leukocyte (PMNL) functions and stimulates lactoferrin in
      PMNL inhibition of candidal growth.
AB  - Mannoprotein fractions of Candida albicans were assayed for their effects on the
      anticandidal activity of human polymorphonuclear leukocytes (PMNL). One fraction,
      MP-F2, enhanced PMNL inhibition of candidal growth in vitro as potently as
      bacterial lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating
      factor (GM-CSF), and interleukin-8. MP-F2-mediated PMNL activation was manifested
      on yeast and mycelial forms of the fungus, required the integrity of the mannan,
      and was due to an increase in the actual number of phagocytic PMNL rather than to
      a greater ingestion of fungal cells by each individual neutrophil. While not
      inducing augmented O2 production or degranulation of azurophilic granules, MP-F2
      strongly stimulated the release of lactoferrin. Lactoferrin inhibited candidal
      growth in the absence of PMNL, and anti-lactoferrin antibodies reversed both this
      inhibition and the PMNL activation by MP-F2, GM-CSF, and LPS. Thus, PMNL may be
      activated by relevant candidal mannoproteins, and release of lactoferrin may add
      to other antimicrobial mechanisms of PMNL for the control of candidal infections.

PMID- 1402023
TI  - Expression and characterization of a cDNA clone encoding an immunodominant
      surface glycoprotein of Pneumocystis carinii.
AB  - Most studies of antigens of Pneumocystis carinii have focused on an abundant,
      immunogenic 95- to 140-kDa surface glycoprotein referred to as gpA. Expression
      cloning of gpA from P. carinii obtained from ferrets resulted in isolation of
      colinear fragments of gpA cDNA encoding approximately 87 kDa of the core protein.
      Northern hybridization detected an abundant, single species of gpA-specific mRNA
      of 3600 nucleotides. Southern hybridization revealed gpA-specific bands only in
      P. carinii-infected lung genomic DNA, suggesting that gpA cDNA did not result
      from induction of a host lung gene. Antiserum raised against a fragment of
      recombinant gpA detected P. carinii cysts and isolated native P. carinii gpA,
      indicating retention of epitopes between the nonglycosylated recombinant gpA and
      glycosylated native gpA. The deduced amino acid sequence is hydrophilic and
      contains 12 potential N-linked glycosylation sites and 47 cysteine residues,
      consistent with the surface orientation of gpA on the organism and other known
      characteristics of the native molecule.

PMID- 1402024
TI  - Epidemiology of visceral leishmaniasis in northeast Brazil.
AB  - Epidemiologic aspects of the relationship between infection with Leishmania
      chagasi and development of clinical visceral leishmaniasis (VL) were studied in
      all children < 11 years old in a defined, endemic, rural area of the state of
      Ceara in northeast Brazil. Antileishmanial antibodies were measured in the same
      subjects by ELISA on six occasions between May 1987 and August 1989.
      Seroconversion was documented during this period in 108 children, with a
      cumulative annual incidence of 4.6%. Twelve (11.1%) of these children developed
      VL. Age < 4 years, hematocrit < 33%, and living in the mountains predicted the
      development of clinically apparent VL after seroconversion. Despite a high
      percentage of dogs serologically positive in the region (38%), there was no
      increased risk of infection for children living in the same household with dogs.
      Since children in households with a prior case of VL had a threefold increased
      risk of infection, human-sandfly-human transmission might have been important.

PMID- 1402025
TI  - Migration of 75Se-methionine-labeled Schistosoma japonicum in normal and
      immunized mice.
AB  - The patterns of migration and attrition of Schistosoma japonicum larvae were
      studied in a mouse model. Control and immunized mice were challenged with 100 S.
      japonicum cercariae tagged with 75Se-labeled methionine. Skin, lungs, liver, and
      other organs were analyzed by compressed organ autoradiography for the presence
      of larvae that appeared as reduced silver foci. The pattern of migration of S.
      japonicum was similar in mice with primary infection and in mice immunized with
      irradiated cercariae. Skin was not a site of attrition after primary infection
      nor after immunization. Attrition occurred after migration to the lungs and
      continued until after migration to the liver in mice with primary infection,
      while in immunized mice attrition occurred before lung migration and continued at
      a faster rate than in normal mice. In both control and immunized mice, the lungs
      and liver were the major sites of attrition.

PMID- 1402027
TI  - Diagnosis of vertical human immunodeficiency virus type 1 infection by whole
      blood culture.
AB  - The qualitative and quantitative performance of a human immunodeficiency virus
      type 1 (HIV-1) whole blood culture method was assessed for use in the diagnosis
      of vertical HIV-1 infection. This method requires < 1 mL of whole blood and
      allows for the quantification of blood virus load. HIV-1 was isolated from 36
      (95%) of 38 whole blood specimens from 27 HIV-1-infected children compared with 0
      of 16 whole blood specimens from 16 uninfected children. HIV-1 titers were
      significantly higher in severely symptomatic children (2450 TCID/mL) than in less
      symptomatic children (179 TCID/mL). This simple quantitative culture assay may be
      useful for the early diagnosis of vertical HIV-1 infection, the assessment of
      blood virus load, and the evaluation of antiretroviral therapies.

PMID- 1402026
TI  - Incidence of zidovudine-resistant human immunodeficiency virus isolated from
      patients before, during, and after therapy.
AB  - The zidovudine sensitivity of 372 isolates of human immunodeficiency virus (HIV)
      obtained from 237 patients before, during, and after treatment with zidovudine
      was examined. Virus resistant to > 0.5 micrograms/mL (1.87 microM) zidovudine was
      isolated from most patients (93%) after 36 months of therapy. Zidovudine
      sensitive virus was isolated from 5 of 15 patients who had ended antiretroviral
      therapy but had previously shed resistant virus. The emergence of sensitive virus
      after end of therapy appeared to be influenced by both the duration of treatment
      and the time off drug. Patients with resistant virus tended to have low CD4 cell
      counts and HIV antigenemia at the commencement of therapy, suggesting that these
      two factors are important in the development of drug resistance.

PMID- 1402028
TI  - Initial low CD4 lymphocyte counts in recent human immunodeficiency virus
      infection and lack of association with identified coinfections.
AB  - Initial CD4 lymphocyte counts were studied in 244 patients with human
      immunodeficiency virus (HIV) seroconversion. The CD4 cell counts at initial
      presentation after seroconversion were normally distributed (mean, 579/mm3; SD,
      252). The mean percentage of CD4 cells was 26.1% (SD, 5.6). CD4 cell counts were
      < 500/mm3 in 41% and < 200/mm3 in 4%. The mean calculated duration of HIV
      infection was 7.7 months, which was not significantly different between the
      highest and lowest CD4 count quartiles (8.1 vs. 7.9). Age, sex, race, and
      serologic evidence of toxoplasmosis, cytomegalovirus, hepatitis B, syphilis, and
      varicella-zoster virus were not associated with initial low CD4 cell counts;
      however, never-married men were significantly overrepresented in the lowest
      quartile. These findings suggest that extensive CD4 lymphocyte depletion is
      common in early HIV infection and that frequent screening is necessary to
      identify newly infected patients who would benefit from antiretroviral therapy.

PMID- 1402029
TI  - Immune activation during measles: beta 2-microglobulin in plasma and
      cerebrospinal fluid in complicated and uncomplicated disease.
AB  - Beta 2-microglobulin (beta 2m) is a small protein that forms the light chain of
      the class I major histocompatibility molecule and is also present in soluble form
      in serum and cerebrospinal fluid (CSF). Measles is associated with immune
      activation and evidence of immunologic abnormalities that persist for several
      weeks. To assess further the immunologic changes occurring during measles, beta
      2m was measured in plasma and CSF. beta 2m became elevated during measles before
      the onset of the rash and was highest during the rash. Elevations persisted for
      several weeks and correlated well with levels of soluble interleukin-2 receptor
      and neopterin and less well with soluble CD8. CSF beta 2m was elevated in
      postmeasles encephalomyelitis. Plasma levels of beta 2m did not correlate with
      spontaneous proliferation of peripheral blood mononuclear cells (PBMC) or with in
      vitro production of beta 2m by cultured PBMC. The data suggest that increases in
      beta 2m in measles correlate better with cytokine production than with cell
      proliferation.

PMID- 1402030
TI  - Genotyping of Chlamydia trachomatis from a trachoma-endemic village in the Gambia
      by a nested polymerase chain reaction: identification of strain variants.
AB  - Direct amplification of the major outer membrane protein (MOMP) gene by
      polymerase chain reaction (PCR) was used to identify Chlamydia trachomatis in eye
      swabs from clinically active cases of endemic trachoma in a Gambian village.
      Chlamydial DNA was detected in 51% of 96 subjects with clinically active disease
      and in 5% of 37 clinically negative individuals. The PCR detection was combined
      with typing, using nested primers to variable sequences (VS) 1, 2, and 4 of the
      MOMP genes to distinguish between trachoma genotypes A, B, and C, respectively.
      Genotypes A and B were detected in the village, with some individuals harboring
      both genotypes within the same eye. DNA sequencing revealed strain variants of
      both genotypes. Typing of genotype and strain variants is now in progress to
      study trachoma transmission within the village.

PMID- 1402032
TI  - An analysis of the quantitative relationship between oral temperature and
      severity of illness in experimental shigellosis.
AB  - The relationship between oral temperature and other parameters of illness was
      examined in 139 adult volunteers infected experimentally with Shigella sonnei. In
      subjects developing clinical disease, peak temperature correlated positively with
      total number of signs and symptoms other than fever (rxy = .71, P < .001), stool
      volume (rxy = .41, P < .001) and number of stools produced during the illness
      (rxy = .46, P < .001). Peak temperature correlated negatively with incubation
      period (rxy = -.34, P = .007) but exhibited no apparent correlation with duration
      of illness. The average oral temperature during illness correlated positively
      with number of other signs and symptoms of infection but not with stool volume or
      stool number. These results suggest that in clinical investigations involving S.
      sonnei, and perhaps with other pathogenic microorganisms, oral temperature is a
      useful quantitative marker for estimating disease severity.

PMID- 1402031
TI  - Evaluation of polymerase chain reaction, tuberculostearic acid analysis, and
      direct microscopy for the detection of Mycobacterium tuberculosis in sputum.
AB  - Tuberculosis remains a major global cause of morbidity and mortality. There is an
      urgent need for improved bacteriologic diagnosis of Mycobacterium tuberculosis
      infection. Three methods for rapid identification of M. tuberculosis in sputum
      samples (direct microscopy, gas chromatography-mass spectrometry [GC-MS], and
      polymerase chain reaction [PCR]), were compared with culture on Lowenstein-Jensen
      medium. Growth of M. tuberculosis was observed in 38 of 145 sputum samples.
      Detection of acid-fast bacilli by direct microscopy gave a sensitivity of 66% and
      a specificity of 100%. Detection of tuberculostearic acid by GC-MS gave a
      sensitivity of 55% and a specificity of 87%. Amplification by PCR of a fragment
      of the insertion sequence IS6110 gave a sensitivity of 95% and a specificity of
      93% compared with culture and a corrected specificity of 99% compared with both
      culture and clinical data. This study indicates that PCR can be adapted for
      clinical use and is the method of choice for rapid diagnosis of pulmonary
      tuberculosis.

PMID- 1402033
TI  - Serum concentrations of penicillin, doxycycline, and ciprofloxacin during
      prolonged therapy in rhesus monkeys.
AB  - Concentrations of penicillin, doxycycline, and ciprofloxacin were measured by
      bioassay in sera of rhesus monkeys treated with these drugs for inhalation
      anthrax. Antibiotic doses were determined on the basis of published serum
      concentration data from humans and comparative body surface area calculations for
      humans and rhesus monkeys. The antibiotics were well tolerated. Serum peak and
      trough concentrations of penicillin, doxycycline, and ciprofloxacin,
      respectively, averaged 2.7 and 0.8, 1.31 and 0.26, and 1.22 and 0.14
      microgram/mL. These were within the range usually observed with standard oral
      doses in humans, and peak concentrations in all monkeys exceeded the MICs for 90%
      of Bacillus anthracis strains.

PMID- 1402034
TI  - Transfer of pheromone-inducible plasmids between Enterococcus faecalis in the
      Syrian hamster gastrointestinal tract.
AB  - Pheromone-responsive plasmids are common to Enterococcus faecalis, transfer at
      high frequency in vitro, and carry cytolysin and other gene products implicated
      in the pathogenesis of enterococcal infection. A Syrian hamster model of
      enterococcal intestinal overgrowth was used to test for transfer of three
      isogenic plasmids differing in conjugative and cytolytic phenotypes.
      Transconjugants were found in 8 (44%) of 18 and 6 (35%) of 17 hamsters given
      donor strains containing cytolytic (pAM714) and noncytolytic (pAM771) pheromone
      responsive plasmids. Of the 14 hamsters from which transconjugants were isolated
      from stool, 9 (64%) had transconjugants 1 day after donor strain inoculation. The
      frequency of transfer (mean +/- SD) for pAM714 and pAM771 was 1.4 +/- 2.2 x 10(
      1) and 2.9 +/- 4.2 x 10(-2) transconjugants/donor, respectively (P > .20).
      Transconjugants were not recovered from hamsters receiving a cytolytic,
      nonconjugative plasmid (pAM930; transfer frequency < 2 x 10(-5)
      transconjugants/donor). Pheromone-responsive plasmid transfer between E. faecalis
      strains occurs at high frequency in the gastrointestinal tract of hamsters and
      may be one means by which enterococcal resistance and virulence factors
      disseminate.

PMID- 1402035
TI  - Acquired immunity to systemic candidiasis in immunodeficient mice: role of
      antibody to heat-shock protein 90.

PMID- 1402036
TI  - Encephalitis, not cerebral malaria, is likely cause of coma with negative blood
      smears.

PMID- 1402037
TI  - Amphotericin B-resistant Candida albicans.

PMID- 1402038
TI  - Storage as a factor in enumeration of CD4+ lymphocytes.

PMID- 1402039
TI  - Retreatment of chronic hepatitis C with interferon-alpha.

PMID- 1402040
TI  - Effect of human immunodeficiency virus infection on cell-mediated immunity in
      tuberculosis.

PMID- 1402041
TI  - Increased tumor necrosis factor-alpha levels in Argentine hemorrhagic fever.

PMID- 1402042
TI  - Granulocyte-macrophage colony-stimulating factor synthesis during experimental
      endotoxemia in humans.

PMID- 1402043
TI  - The incidence of Trichomonas vaginalis in chronic prostatitis patients determined
      by culture using a newly modified liquid medium.

PMID- 1402044
TI  - Isolation and characterization of 115 street rabies virus isolates from Ethiopia
      by using monoclonal antibodies: identification of 2 isolates as Mokola and Lagos
      bat viruses.
AB  - There were 115 isolates of rabies viruses recovered by tissue culture technique
      from 119 animal brains collected in Ethiopia. By using 17 selected
      antinucleocapsid monoclonal antibodies (MAbs), 113 isolates were classic street
      rabies viruses (serotype 1). An isolate of feline origin (Eth-16) was a Mokola
      virus (serotype 3) and another isolate (Eth-58, obtained from a rabid dog) was
      serotype 2 (Lagos bat virus). None of the 16 antiglycoprotein MAbs used
      neutralized the Eth-16 isolate, whereas Eth-58 was neutralized by 1 (TERA543).
      Antirabies vaccines prepared from Pitman-Moore and Pasteur virus strains
      protected mice against homologous challenge, but neither was protective against
      the 2 rabies-related virus isolates. The isolation of Mokola and Lagos bat
      viruses from domestic animals in eastern Africa is of public and veterinary
      concern mainly due to lack of effective vaccines against these agents and the
      difficulty of proper diagnosis.

PMID- 1402045
TI  - Reconstructive surgery: function versus aesthetics?

PMID- 1402046
TI  - Long-term results on the quadrangular osteotomy.
AB  - The results of a follow-up study of 17 patients who underwent a quadrangular
      osteotomy, are presented. The indication for a quadrangular osteotomy includes a
      hypoplastic maxilla with retruded infra-orbital rims and infra-orbital area, but
      with normal nose projection. Almost all patients were satisfied with the result.
      Relapse in a horizontal direction appeared to be approximately 12%; however,
      considerable relapse was seen in the vertical direction (61.7%-158%). A major
      problem during operation appeared to be the high rate of fractures of the infra
      orbital wing. Sensory loss in the area of the infra-orbital nerve occurred in 79%
      of the operated sides. Four patients needed surgical correction of conditions
      that should be considered complications resulting from the osteotomy, including a
      case of partial ischaemic necrosis of the premaxilla in a BCLP patient.

PMID- 1402048
TI  - Occlusion of the incisal canal with bone chips. A procedure to facilitate
      insertion of implants in the anterior maxilla.
AB  - In 4 patients, who had lost one or both central maxillary incisors due to trauma,
      the incisal canals were filled with autogenous cancellous bone harvested from the
      chin. After a healing period of 4-5 months implants were inserted. At the time of
      implant surgery in all cases the canal appeared to be replaced by cancellous bone
      and the implants were placed partially into the grafted area. After another 6
      months abutments were connected and crowns made. After follow-up of between 12
      and 15 months no fixture has been lost.

PMID- 1402047
TI  - Computerized cephalometric orthognathic surgical simulation, prediction and
      postoperative evaluation of precision.
AB  - A new computerized, cephalometric, orthognathic surgical program (TIOPS) has been
      evaluated in surgical simulation, prediction and postoperative assessment of
      precision. Records of 10 consecutive patients admitted for orthognathic surgical
      treatment were analysed and prediction plans produced by computerized surgical
      simulation. Predicted and postoperative positions of maxilla and mandible were
      compared with linear and angular measurements. No statistically significant
      differences between predicted and postoperative positions could be demonstrated
      (p greater than 0.05).

PMID- 1402049
TI  - Posterior dislocation of mandibular condyle into external auditory canal. A case
      report.
AB  - A case is reported of a 49-year-old edentulous patient who suffered a posterior
      dislocation of the right fractured mandibular condyle causing a fracture of the
      tympanic plate. This was associated with a right transverse fracture of the
      petrous bone and an intact tympanic membrane. Some of the problems related to
      this condition are discussed.

PMID- 1402050
TI  - Applications of the lateral vastus muscle flap.
AB  - The lateral vastus muscle flap has the potential to become one of the most
      appropriate free flaps for reconstructive surgery in the oral maxillofacial area
      in selected cases. The flap is relatively easy to harvest and gives rise to
      little donor site morbidity. The quality of the large diameter vessels allows for
      relatively easy microsurgical anastomosis. Nerve anastomosis is possible, which
      makes it extremely suitable for tongue reconstruction.

PMID- 1402051
TI  - Neoplastic disease in the head and neck of patients with AIDS.
AB  - Immunosuppression increases the risk of developing malignancies. In
      immunosuppression due to human immunodeficiency virus (HIV) disease the common
      head and neck tumors are Kaposi's sarcoma and non-Hodgkin's lymphoma. Squamous
      cell carcinoma has also been reported. Kaposi's sarcoma is the commonest
      neoplastic disease in AIDS. The incidence of lymphoma is rapidly increasing. This
      article reviews the incidence, clinical presentation and management of these
      diseases in the head and neck in AIDS patients.

PMID- 1402052
TI  - Investigating a lingual thyroid.
AB  - During a 15-year-period, in a thyroid investigation centre in Sri Lanka
      comprising 16,593 cases, 8 lingual thyroids were seen. All patients were female.
      Radioisotope studies and scintiscanning performed during the investigations of
      these cases are presented. All subjects were euthyroid at presentation and the
      clinical courses of 5 cases during follow-up are discussed.

PMID- 1402053
TI  - Giant ossifying fibroma. Case report on a bimaxillary presentation.
AB  - Ossifying fibroma is a slow-growing, benign neoplasm, but some lesions behave
      aggressively, reaching massive proportions, thus demanding special treatment. The
      following case report holds particular interest, because of the simultaneous
      occurrence of an active ossifying-cementifying fibroma in the maxilla and
      mandible with the maxillary lesion attaining enormous size.

PMID- 1402054
TI  - Necrotizing fasciitis of the neck and chest. Report of a case.
AB  - A case is presented of necrotizing fasciitis of the neck and chest characterized
      by rapid progressive necrosis of subcutaneous tissue, fascia and skin. The
      diagnosis and management is discussed.

PMID- 1402055
TI  - Effect of marrow perforation on the sheep temporomandibular joint.
AB  - The effect of surgically perforating the mandibular condyle to allow synovial
      fluid to contact the marrow was examined in 5 sheep temporomandibular joints. The
      surgical defect showed replacement of the marrow with fibro-osseous tissue and
      subcortical cysts. A vertical, central osteophyte emerged from the perforation,
      causing attenuation or perforation of the disc and temporal surface
      proliferation. These changes were radiographically and histologically similar to
      advanced osteoarthritis. This supports the concept that intraarticular micro or
      macrofracture may result in osteoarthritis.

PMID- 1402056
TI  - [Activation of aerobic bacteria used as BOD measurement of seawater].
AB  - Waste of seawater used for cooling water for machines in some kinds of industries
      in a littoral district in Sakai City, comes under the application of BOD control
      of the pollution control ordinance in Osaka Prefecture. But unfortunately the BOD
      measurement method of seawater sample has not been established. In order to
      establish the measurement method, we studied the strength of activation of
      aerobic bacteria in the incubation water used and the dilution water. From our
      results it was proved that we can use the incubation seawater consisting of more
      than 10(3) cells/ml general bacteria count and more than 0.50 microgram/l ATP
      (Adenosin triphosphate) as the incubation water and the artificial seawater as
      the dilution water.

PMID- 1402057
TI  - [Recurrent case of subacute necrotizing lymphadenitis in young man].
AB  - A 10-year-old male was admitted to our hospital because of lymphadenopathy and
      fever. Biopsy of a cervical lymph node demonstrated nodular necrotic foci
      containing many macrophages phagocyting the karyorrhexic nuclei. He was diagnosed
      as subacute necrotizing lymphadenitis (SNL) and all the symptoms disappeared
      spontaneously within a month. Five year later, lymphadenopathy recurred, and re
      biopsy showed the same histological findings and he also recovered spontaneously.
      Although the prognosis of SNL is generally excellent and the majority of the
      patients recover without any treatment, recurrences are very rare, especially in
      young male patient.

PMID- 1402058
TI  - [Correlation between hepatitis B virus infection and chronic liver disease in
      Okinawa].
AB  - In Okinawa prefecture, prevalence of hepatitis B surface antigen (HBsAg) among
      blood donors is 3.5% and is twice as high as the average for the whole of Japan
      (1.5%), and is the highest in Japan (p less than 0.005). In contrast, mortality
      rates of both liver cirrhosis (LC) and primary liver cancer (PLC) in Okinawa are
      the lowest in Japan. Many epidemiological studies have shown that the positive
      rate of HBsAg correlates with mortality rate of PLC. To elucidate the cause of
      this epidemiological discrepancy, cross-sectional seroepidemiological studies and
      a prospective clinical study were conducted. In the cross-sectional studies, the
      following results were obtained; (1) Positive rate of HBsAg among patients with
      LC in Okinawa was 15.2% and lower than the average for the whole of Japan
      (23.4%). A similar comparison among patients with hepatocellular carcinoma showed
      24.4% in Okinawa Vs. 31.4% in the whole of Japan. (2) The age-specific hepatitis
      B e antigen positive rate among 829 HBsAg positive health examinees tend to
      decrease with increase in age; 50% in less than 20 years old age group, 15.7% in
      third decade and 2-3% or less in 30 or more age group. Of the 829, 431 HBsAg
      positive subjects were referred our liver out-patient clinic. Then, of the 431,
      27 (6.3%) were diagnosed or suspected as having chronic hepatitis and one (0.2%)
      was diagnosed as having cirrhosis. Of the 431, 381 (88.4%) were diagnosed as
      healthy HBsAg carrier, the great majority (94.0%) of whom had positive reaction
      of anti-HBe antibody and normal values of both GOT and GPT.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1402060
TI  - [Clinical and epidemiological aspects of enteritis due to Salmonella hadar. II.
      Environmental contamination by Salmonella hadar in Shizuoka Prefecture--studies
      on the feasibility of reducing S. hadar infection].
AB  - A systematic examination was performed for environmental food contamination by
      Salmonella in poultry farms, broiler chickens, broiler processing plants and meat
      on the market. Salmonella was isolated from 219 of 1197 samples and the serotypes
      showed a wide distribution. (Table 1-1). S. hadar accounted for 37.1% (96) of all
      isolations (259). The contamination rate of broiler chickens on arrival at
      broiler processing plants is relatively low. However, in the broiler processing
      plants, containers, processing machinery, cooling water and slaughters were
      highly contaminated by Salmonella, S. hadar being the most prominent serotype in
      the plants. 64% of chicken meat on the market was contaminated by Salmonella, S.
      hadar being the second most prominent serotype. 11% of the pork and none of the
      beef or horseflesh was contaminated by Salmonella. These results indicate that
      poultry is the main source of S. hadar infection in humans. However, no S. hadar
      was isolated from cultures of 119 samples of feed for chickens from each delivery
      (Table 1-1). Thus, as the main source of infection by S. hadar of broiler
      chickens, an association with the feed seems to be ruled out. S. hadar was
      isolated at three of 18 poultry farms within Shizuoka Prefecture. Follow-up
      studies were performed at the three poultry farms which revealed that in two of
      them, Salmonella was completely eradicated on completion of disinfection. In the
      other one farm, which is still being disinfected, various strains of Salmonella
      including S. hadar still survived. We conclude that the main cause of the problem
      is the magnification of contamination of Salmonella-free material during the
      process at the broiler processing plants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402059
TI  - [Clinical and epidemiological aspects of enteritis due to Salmonella hadar. I.
      Isolation of S. hadar from sporadic diarrhea--clinical and bacteriological
      study].
AB  - Before 1983, S. hadar was seldom isolated from man, animals, food or the
      environment in Japan: only one strain having been isolated from man and one from
      the environment. In subsequent years there has been a progressive increase in the
      number of isolations. S. hadar is now one of the commonest serotypes isolated
      from cases of sporadic diarrhea in Shizuoka Prefecture (Table 1). However, the
      epidemiology of S. hadar is not clearly understood. Reports on the clinical
      features of S. hadar gastroenteritis are also scarce. We examined the clinical
      symptoms of 15 cases of S. hadar gastroenteritis. S. hadar was encountered in
      patients of all ages. Infants and young children below 10 years of age
      constituted 47% of all cases. Seventy per cent of young children below 10 years
      of age experienced fever of more than 39 degrees C. This incidence was
      significantly higher than that of general Salmonella gastroenteritis observed in
      our previous study, in which fever of more than 38 degrees C was noted in 61% of
      the children. We found one case of presumptive person-to-person spread. No other
      household contacts of index patients suffered from diarrhea during the same
      period. Systematic examination for Salmonella contamination was performed for
      poultry farms, broiler chickens, broiler processing plants and meat on the
      market. 259 Salmonella strains were isolated from 1197 samples. S. hadar
      accounted for 37.1% (96) of all isolations (259). A drug resistance test was
      performed for 51 strains of the diarrhea cases and 67 strains of the environment.
      The pattern of the distribution of MICs of 9 drugs was similar in the two
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402061
TI  - [Genetic identification of 25 Legionella species by modified microdilution plate
      hybridization, and its evaluation with isolated strains].
AB  - Modified microdilution plate hybridization was used for genetic identification of
      25 Legionella species. The cell wall of the isolate was broken down by glass
      beads. And the DNA was extracted, labeled photo-reactive biotin, and hybridized
      with reference DNAs immobilized in microdilution wells. Hybridized DNAs were
      detected by colormetric method. Each type strain of 25 Legionella species was
      clearly differentiated by this method. Among 103 clinical and environmental
      Legionella strains, 97 strains were genetically identified by this method. 60
      strains were identified as the same species as by the conventional method.
      Concerned with ten strains that had been serologically identified as L.
      bozemanii, two strains isolated from the human lung were genetically identified
      as L. bozemanii, but the remaining environmental 8 strains were identified as L.
      anisa. Among the 35 strains of legionellae that had been unidentified at species
      level, by physiological and serological tests, 27 strains were genetically
      identified as L. pneumophila, 1 strains as L. feeleii, and another, as L. anisa,
      but 6 strains were not identified. We found that three strains among the 6
      strains belong to a single species of genus Legionella other than the 25
      reference species used in this study.

PMID- 1402062
TI  - [Study of the anti Borrelia burgdorferi antibody of hunters in Hokkaido].
AB  - We examined the sera of 587 hunters in Hokkaido (Japan's northernmost island) for
      the antibody to Borrelia burgdorferi (B. burgdorferi) by enzyme immunoassay,
      clarified the conditions related to antibody positivity in these subjects
      according to region, and studied the effects of factors such as age and lifestyle
      on the antibody titer. In contrast with an anti-B. burgdorferi antibody positive
      rate of 7.1% in control sera, that in the hunters' sera was 16.0%. Among those
      positive for the anti-B. burgdorferi antibody, the antibody positive rate in sera
      excluding those testing positive in the serological test for syphilis was 5.5% in
      the controls, and 15.4% in the hunters, the latter rate being significantly
      higher (p less than 0.05). In both hunters and control groups, the antibody
      positive rate tended to be higher in older subjects, but the antibody titer
      showed no correlation with their age, or the duration of their hunting
      experience. Examination of the hunters' occupations revealed a tendency toward
      high titers in those engaged in dairy farming. The antibody positivity of those
      who went gathering edible wild plants was significantly higher than those did not
      (p less than 0.05). These observations suggested that the high antibody-positive
      rate in hunters may have been due largely to the effect of activities other than
      hunting as sources of infection by Borrelia.

PMID- 1402063
TI  - [In vitro antimicrobial activity of DR-3355, a new quinolone antibacterial agent,
      against clinical isolates of enteritis-causing bacteria].
AB  - We determined the minimum inhibitory concentration (MIC) of DR-3355, a newly
      developed quinolone-derivative antibacterial agent, against clinical isolates of
      various bacterial species from enteritis patients, and compared them with those
      of ofloxacin (OFLX), ciprofloxacin (CPFX), nalidixic acid (NA), ampicillin
      (ABPC), kanamycin (KM). MIC90 of DR-3355 against 94 strains of Shigella spp. and
      5 strains of Escherichia coli, 36 strains of Salmonella spp., 22 strains of
      Vibrio cholerae, 5 strains of Vibrio parahaemolyticus, and 19 strains of
      Campylobacter jejuni were 0.05, 0.10, 0.0025, 0.39, and 0.78 micrograms/ml,
      respectively. These values were 1/2 of that of OFLX, and two times of that of
      CPFX. MIC90 of DR-3355, OFLX and CPFX against C. jejuni were 0.78 micrograms/ml.
      MIC90 of DR-3355 against isolates from enteritis patients except for Vibrio spp.,
      were 1/30 to 1/60 of those of NA, ABPC, and KM.

PMID- 1402064
TI  - [Significance of the combined treatment with isepamicin and piperacillin in an in
      vitro model for complicated cystitis operated by automatic simulator apparatus
      for urinary concentration].
AB  - Isepamicin (ISP) and piperacillin (PIPC) were shifted to the urinary
      concentration by employing an in vitro complicated cystitis model operated by a
      computer-controlled automatic simulator for urinary concentration, and
      administrated to bacteria in the urinary bladder model (Pseudomonas aeruginosa:
      P. aeruginosa, initial cell concentration: 10(7) cfu/ml). In this case, effects
      by single treatment with ISP or PIPC on cell number curves were examined.
      Further, significance of the combined treatment with ISP and PIPC were
      investigated by changing the order of each treatment. And following the results
      were obtained. 1. In a single treatment with PIPC the cell concentration was
      minimum (10(4) cfu/ml) at 9th hour after its treatment and thereafter, regrowth
      to the same level as the initial concentration was observed at 16th hour. 2. In
      the case of single treatment with ISP, the cell concentration became minimum
      (10(2) cfu/ml) at 13th hour after the treatment and raised to the same
      concentration as the initial one at 25th hour. 3. In the combined treatment, the
      cell concentration was minimum (less than 10(1) cfu/ml) at 26th hour in the case
      of prior treatment with ISP. Thereafter, regrowth was observed and the cell
      concentration at 42nd hour reached to the initial cell concentration. 4. In
      simultaneous treatment with ISP and PIPC, the cell concentration at 24th hour was
      minimum (10(1) cfu/ml) and reached to the same level as the initial one after
      regrowth. From these results, it was found that the combined treatment with ISP
      and PIPC caused more reduction of the cell concentration than either single
      treatment. Further, regrowth of the cells was suppressed for longer
      duration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402065
TI  - [Evaluation of chlamydial IgM antibodies for clinical diagnosis].
AB  - Chlamydia trachomatis (C. trachomatis), C. psittaci, and C. pneumoniae are now
      well established as pathogens of respiratory infections including pneumonia.
      Serum samples from 223 infants and children with pneumonia, 31 patients with
      adult inclusion conjunctivitis, 16 parents of babies with neonatal inclusion
      conjunctivitis and others were tested for IgM antibodies to Chlamydiae.
      Diagnostic kits for chlamydial IgM antibodies (SeroELISA and IPAzyme) have been
      also evaluated for their diagnostic value. It was found that detection of
      specific IgM antibodies with SeroELISA has a diagnostic value in chlamydial
      pneumonias.

PMID- 1402066
TI  - [Identification of mycobacteria by the acridinium-ester labeled DNA probes for M.
      tuberculosis and M. avium-intracellulare complex in culture and its clinical
      application].
AB  - The detectability of mycobacterium in culture by non-isotopic, chemiluminescent
      DNA probes for Mycobacterium tuberculosis (M. tuberculosis) and M. avium
      intracellulare complex (MAC) was evaluated and compared with that by 125I-labeled
      DNA probe for the same mycobacteria. The sensitivity and specificity of the AE
      DNA probes for MAC were 97.2% and 100%, respectively, for the conventional method
      and were both 100% for the 125I-labeled DNA probes. The detection limits of the
      AE-DNA probes tests for both M. tuberculosis and MAC were 10(5)-10(6) CFU/tube
      which were almost the same as those of the 125I-labeled DNA probes tests. Because
      the procedure is simple, rapid (it can be completed within 90 min), and safe (it
      does not use radioisotopes), it can be easily performed in any clinical
      laboratory.

PMID- 1402067
TI  - [Four cases of respiratory tract infections caused by Corynebacterium
      pseudodiphtheriticum].
AB  - Four cases of respiratory tract infections caused by Corynebacterium
      pseudodiphtheriticum were reported. The first two patients developed pneumonia
      with Corynebacterium pseudodiphtheriticum during steroid therapy used against
      their underlying diseases. The other two patients had acute exacerbation of
      chronic pulmonary diseases caused by C. pseudodiphtheriticum. These four patients
      improved by antibiotic therapy. Though nondiphtheria corynebacteria are regarded
      as "normal flora" when they are isolated from sputum, they should be recognized
      as potential pathogens.

PMID- 1402068
TI  - [A case of miliary tuberculosis (miliary TB) accompanied with adult respiratory
      distress syndrome (ARDS) in a patient with Cushing's syndrome].
AB  - A 74-year-old housewife was admitted to the hospital with complaints of high
      fever and general fatigue. The physical examinations on admission showed no
      particular findings except for mild hepatomegaly, but laboratory findings showed
      severe liver dysfunction, active inflammation and negative tuberculine test. On
      the 4th day, she suddenly complained of severe respiratory distress. A chest X
      ray film demonstrated surprising changes in comparison with that taken on
      admission. On suspicion of adult respiratory distress syndrome (ARDS) associated
      with military tuberculosis (Miliary TB), administration of Methylpredonisolone
      (1000 mg a day for 3 days) in addition to antituberculous drugs was immediately
      started. With this therapy she was recovered from such ill condition, but the
      general exhaustion and slight fever continued. We suspected that her condition
      might be due to adrenocortical involvement of Miliary TB and hormonal
      examinations were performed. Unexpectedly, Cushing's syndrome was suspected on
      the basis of the following; high level of plasma cortisol without normal daily
      variation, normal ACTH level, an absent response to the Dexamethasone suppression
      test. Computed tomography revealed left side adrenal mass. During these
      examinations, renal dysfunction probably due to Miliary TB grew gradually worse
      and she died of renal failure on the 56th day. Necropsy revealed disseminated
      tuberculosis involving the lungs and the liver, but the adrenal glands were not
      examined.

PMID- 1402070
TI  - [Enteropathogenicity and enteropathogenic toxin production of Vibrio mimicus].
AB  - Enteropathogenicity and enteroreactive-toxins were examined in 66 strains of
      Vibrio mimicus and the following results were obtained. Frequencies of
      enteropathogenic strains judged by the result of suckling mouse tests were 11/13
      (85%) for clinical isolates and 37/53 (70%) for fish or environmental isolates.
      Frequencies of preservation of cholera toxin gene and NAG-ST gene were 2 and 15%,
      respectively, for 48 enteropathogenic strains, and 0 and 6%, respectively, for 18
      non-enteropathogenic strains. Frequencies of production of NAG-rTDH, FAF and
      hemolysin were 4, 63 and 100%, respectively, for 48 enteropathogenic strains, and
      6, 50, and 100%, respectively, for 18 non-enteropathogenic strains. No
      correlation between serovar and enteropathogenicity was observed in the suckling
      mouse test. Six out of 12 enteropathogenic strains produced hemolysin in ligated
      rabbit ileal loop, while 1 out of 12 non-enteropathogenic strains did so under
      the same condition. A significant inhibition of fluid accumulation in the ligated
      rabbit ileal loop test with viable cells was noted in rabbits immunized with
      hemolysin of non-O1 V. cholerae. These results suggest that approximately two
      thirds of environmental isolates are enteropathogenic and that hemolysin is the
      most important toxin in the enteropathogenic mechanism of V. mimicus strains.

PMID- 1402069
TI  - [A case of HBsAg positive liver cirrhosis who died after withdrawal of steroid].
AB  - A 42-year-old male was admitted with subarachnoidal hemorrhage. Dexamethasone 224
      mg was used to reduce brain edema. His operation was successful without blood
      transfusion. No remarkable signs and symptoms were found except HBsAg positive
      and mild GPT elevation during his admission. He was discharged on the 33rd day.
      But 2 weeks later, he felt general fatigue and became worse day by day. He was re
      admitted on the 75th day. Several therapies were given but he died of hepatic
      failure on the 85th day. The autopsy showed liver cirrhosis with massive
      necrosis. We believed that the steroid-withdrawal-phenomenon caused excessive
      immunological response and this process caused his hepatic failure leading to
      death.

PMID- 1402071
TI  - [Aztreonam or gentamicin combined with piperacillin as empiric antibiotic therapy
      during neutropenia of patients with hematologic diseases].
AB  - Fourty-two febrile episodes of 32 patients with hematologic disease during
      neutropenia were treated with two randomly assigned antibiotic combinations of
      either piperacillin plus gentamicin or piperacillin plus aztreonam. Eleven of the
      22 febrile episodes treated with piperacillin plus gentamicin and 12 of the 20
      febrile episodes treated with piperacillin plus aztreonam responded. Addition of
      cefamandole to non-responders improved the outcome in 2 of the 16 febrile
      episodes. Mean nadir leucocyte count, age, sex, and underlying disease were not
      significantly different in both groups. Side effects were tolerable in both
      groups, although 1 patient treated with piperacillin plus gentamicin showed
      severe renal impairment. Piperacillin plus aztreonam is as effective as
      piperacillin plus gentamicin as an empiric antibiotic combination in the
      treatment of febrile episodes with hematologic disease during neutropenia.

PMID- 1402072
TI  - [O serogroup and virulence factors of motile Aeromonas].
AB  - A total of 182 isolates of motile Aeromonas from patients with diarrhea and
      environmental sources was investigated for hemolytic activity to rabbit
      erythrocyte and cytotoxicity to HeLa 229 cell. Furthermore, the relation between
      O serogroup and virulence factors, which were lethal to mouse and
      autoagglutination, were investigated. There were many strains possessing both the
      hemolytic and cytotoxic activities in A. hydrophila from overseas traveller's
      diarrhea, suggesting that these activities were associated with intestinal
      pathogenecity. Although there was a clear correlation between hemolytic and
      cytotoxic activities in A. hydrophila from overseas traveller's diarrhea, the
      correlation was not found in A. hydrophila from domestic cases of diarrhea and A.
      sobria from overseas traveller's diarrhea. Especially, some A. hydrophila
      isolates from domestic case of diarrhea produced only hemolysin. These results
      indicated that there was a difference in specificity between the toxins accounted
      for hemolytic and cytotoxic activities, and more than two different toxins were
      developed. O serogroups 11, 34, 14, 16, and 35 in that order were the most
      frequent serogroups. About half of O11 and O34 strains possessed lethal activity
      to mouse. Autoagglutination phenomenon did not seem to be associated with the
      lethal activity. In O11 strains, high cytotoxic titer was more frequently found
      in lethal activity positive-strains than in the activity negative-strains,
      suggesting that cytotoxicity contributed preferentially to lethal activity to
      mouse. But such a correlation was not found in O34 strains, so other virulence
      factors than hemolysin and cytotoxin may be associated with the lethal activity.

PMID- 1402073
TI  - [A clinical study on postantibiotic effect (PAE) and its application to
      chemotherapy for complicated cystitis with an automatic simulator of urinary drug
      concentration].
AB  - In an in vitro complicated cystitis model, the concentrations of the urinary
      antimicrobial agents were determined using a computer-controlled automatic urine
      concentration simulator. The effects on the bacterial count curves showing the
      presence or absence of PAE in antimicrobial agents were studied by comparing the
      times required for regrowth to the concentration at the initial inoculation,
      i.e., effective regrowth time (ERT). The following results were obtained. 1. When
      beta-lactam antimicrobial agents (such as AMPC and CFIX) with no PAE against the
      gram-negative rods were tested, the ERT of the gram-negative rods were about two
      hours shorter than that of the gram-positive coccus. 2. When new quinolone
      antimicrobial agents (such as OFLX) and aminoglycosides (such as ISP) that
      possess PAE against both the gram-positive and negative organisms were used there
      was no difference between ERT of the gram-negative rods and gram-positive coccus.
      Therefore, it was demonstrated that the presence or absence of PAE is also
      reflected in the cell number curve in the case of this in vitro model, more
      closely related to clinical cases, when the antibiotics is simulated in urinary
      concentration shifting.

PMID- 1402074
TI  - Proteus penneri isolated from the pus of a patient with epidural abscess.
AB  - P. mirabilis and P. vulgaris are the two wellknown species in the genus Proteus.
      P. myxofaciens and P. penneri are recent additions to the genus. We isolated P.
      penneri from the pus of a patient with suppurative otitis media and an epidural
      abscess. The characteristics of the organism, including morphology, staining,
      physiology and biochemistry, were studied. Clinical microbiological laboratories
      should suspect P. penneri in the case of as Proteus strain that is negative for
      indole, salicin and esculin, but otherwise resembles P. vulgaris. Proteus
      penneri, formerly known as Proteus vulgaris indole-negative or as Proteus
      vulgaris biogroup 1, was named by Hickman et al in 1932. Little information about
      human infection by this organism is available. In 1982, Hickman and co-workers
      studied 20 strain of P. penneri which were isolated from clinical specimens
      (urine, stool, etc.) in the USA. However, its clinical significance, until
      recently, was unknown. We isolated a strain of P. penneri from the pus of a
      patient with suppurative otitis media and an epidural abscess on June 10 and 15,
      1989. This paper concerns the problems encountered in identifying this organism
      and its clinical significance.

PMID- 1402075
TI  - Misleading serological identification of Legionella anisa as Legionella
      bozemanii.
AB  - Identification of six Legionella species, which we previously identified by
      serological test as Legionella bozemanii (L. bozemanii), was performed by DNA-DNA
      hybridization using a commercial DNA-DNA hybridization kit (Kobayashi Pharm. Co.,
      Japan) introduced by Ezaki et al. All strains were identified as Legionella anisa
      (L. anisa), this being the first identification of L. anisa in Japan.
      Conventional laboratory tests were performed following the DNA-DNA hybridization.
      In this study the results of biochemical examination obtained, corresponded
      closely with those described in previous reports, but the oxidase reaction was
      very weak and varied according to the age of the culture, indicating the
      unreliability of this test in our case. All strains examined under long wave
      ultraviolet (UV) light (366 nm) revealed a blue-white fluorescence, the intensity
      of which ranged from strong to weak. Serological identifications were performed
      by both the slide agglutination test (SAT) and indirect immunofluorescent assay
      (IFA). SAT using commercially available antiserum (Denka Seiken., Japan)
      supposedly specific for L. bozemanii showed cross-reaction between L. bozemanii
      and L. anisa. Hyperimmune rabbit antisera prepared in this study for both L.
      bozemanii and L. anisa, from which cross-reactive antibodies were removed by the
      absorption of each antigen, reacted only with homologous antigens. IFA using a
      commercially available antiserum and hyperimmune rabbit antiserum previously
      described, gave positive reactions with each strain.

PMID- 1402076
TI  - [Studies of serological diagnosis for invasive candidiasis].
AB  - Serological diagnosis was examined for deep mycotic infections, especially
      candidiasis. Candida antigen and antibody researches were made by means of CAND
      TEC (RAMCO Co., Ltd) and passive hemagglutination test (PHA) (Roche Co., Ltd),
      respectively, and simultaneous determinations were made of D-arabinitol, a fungal
      metabolite and (1----3)-beta-D-glucan, fungal parietal component. 1) For normal
      subjects, 1 of 173 cases (0.6%), 5 of 200 cases (2.5%) and 7 of 157 cases (4.5%)
      showed greater than or equal to 1:4, greater than or equal to 320 x and greater
      than or equal to 11 mumol/l for CAND-TEC, Candida antibody and D-arabinitol,
      respectively, and values above these were judged positive. 2) Of the 171 patients
      with pyrexia refractory to general antibiotic agents, who were treated at our
      Department and related institutions from November 1988 to March 1990, 41 with
      obvious Candida infections were CAND-TEC, Candida antibody, D-arabinitol and (1--
      -3)-beta-D-glucan positive in 33 (80.5%), 21 (51.2%), 29 (70.7%) and 13 cases
      (56.6%), respectively. At least one item-positive patient was as high as 97.4%.
      On the other hand, in the group having no Candida infection at all, 1 of 57 cases
      on CAND-TEC (1.7%) and 10 of 55 cases on Candida antibody (18.2%) were positive,
      indicating significant differences from the surely Candida-infectious group. 3)
      Comparative examination of CAND-TEC and other testing methods revealed a
      correlation of CAND-TEC with D-arabinitol in cases showing 1:4 and 1:8 less than
      or equal to, but not other significant difference.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402077
TI  - [Comparison of polymerase chain reaction and enzyme immunoassay (Chlamydiazyme)
      in detection of Chlamydia trachomatis from male urethritis].
AB  - A method using polymerase chain reaction (PCR) was compared to an enzyme
      immunoassay (Chlamydiazyme) for detection of Chlamydia trachomatis by testing a
      reference strain and clinical specimens. Two oligonucleotides based on sequences
      within the major outer membrane protein gene from C. trachomatis serovar L2 were
      used as primers for the PCR. A DNA fragment of 242 bp specific for C. trachomatis
      was amplified by the PCR, when DNA of greater than or equal to 10(2) C.
      trachomatis was used as template for the PCR. A chlamydial antigen was detected
      by Chlamydiazyme, when greater than or equal to 2.6 x 10(3) C. trachomatis were
      applied for the enzyme immunoassay. The PCR method was 26 times more sensitive
      than Chlamydiazyme in detection of C. trachomatis. The PCR method and
      Chlamydiazyme were carried out to examine 74 urethral swabs obtained from male
      patients with urethritis for detection of C. trachomatis. In 45 of 74 specimens,
      the DNA fragment of C. trachomatis was amplified by the PCR, and in 41 of 74, the
      chlamydial antigen was detected by Chlamydiazyme. The detection rate of the PCR
      method (60.8%) was higher than that of Chlamydiazyme (55.4%). The positive
      coincidence rate of the PCR method to Chlamydiazyme was 100% (41/41) and negative
      coincidence rate was 87.9% (29/33). The overall coincidence rate between the two
      methods was high (94.6%). Thus, the PCR method was more sensitive than
      Chlamydiazyme for detection of C. trachomatis and specific for diagnosis of
      chlamydial urethritis.

PMID- 1402078
TI  - [Clinical efficacy of levofloxacin (LVFX) single-dose therapy in female acute
      uncomplicated cystitis].
AB  - Treatment of infections by the use of antimicrobial agents should be made
      essentially in a dose close to the minimally required dose. Acute uncomplicated
      cystitis in female fits as the subject for a single-dose therapy since it is an
      infection reactive relatively easily to antimicrobial agents. Accordingly, an
      assessment has been made regarding the therapeutic results of the single-dose
      therapy in 76 female cases of acute uncomplicated cystitis by the use of LVFX 200
      mg which is a new quinolone. The urinary concentration more than MIC90 to
      Escherichia coli is sustained for about 3 days by this single-dose therapy. As a
      result of judging the therapeutic results from the reactions of the three
      clinical findings of pain on micturition, pyuria and bacteriuria, excellent
      therapeutic results were obtained with effective rates being 100% (76/76) on the
      day 3, 93.9% (46/49) on the day 7 and 94.4% (34/36) on the day 14. The rate of
      cystitic symptoms which recurred posed no problem, being 12.5% (5/40) up to three
      months, as investigated by a questionnaire. As a result of performing close
      urological examinations such as cystoscopy on six cases with insufficient results
      or recurrence, we could detect mild underlying conditions which are considered to
      be intractable factors in the bladder in three cases. From the above results, the
      single-dose therapy of acute uncomplicated cystitis in the female by LVFX which
      is a new quinolone was considered to be an excellent therapeutic drug from its
      characteristics such as its therapeutic results being the same as the
      conventional therapy by daily administration, excellent drug compliance, low
      cost, hard selectiveness of resistant strains, less side effects and furthermore
      it gives the opportunity of detecting a latent and mild underlying condition.

PMID- 1402079
TI  - [An isolation procedure of Chlamydia pneumoniae and Chlamydia trachomatis].
AB  - The author devised a method which permits simultaneous isolation and
      identification of Chlamydia using a slide chamber with 8 wells. Contaminating
      bacteria were eliminated by filtration with the membrane filter. The procedure
      allowed isolation of Chlamydia pneumoniae and Chlamydia trachomatis from 11
      (10.1%) out of 109 and 10 (9.2%) out of 109 otolaryngologic clinical specimens,
      respectively. The use of HL cells together with Hela-229 cells had been
      considered essential to isolate Chlamydia from specimens in this field. The
      conditions for isolating Chlamydia pneumoniae were similar to those for Chlamydia
      trachomatis. The slide chamber procedure with membrane filter treated specimens
      was suitable for simultaneous isolation and culture of various species of
      Chlamydia and allowed easy differentiation of Chlamydia pneumoniae from Chlamydia
      trachomatis with identification by the indirect fluorescent-antibody technique.
      Routine examination of clinical specimens using this procedure should be required
      in the future in order to better understand chlamydial infections.

PMID- 1402080
TI  - [Effect of erythromycin on intrapulmonary influx of neutrophils by intratracheal
      injection of lipopolysaccharide].
AB  - Recently, "low dose and long term" erythromycin (EM) treatment has been reported
      as effective on chronic lower respiratory tract disease, including diffuse
      panbronchiolitis (DPB). However the effective mechanism of EM is still obscure.
      In this study, we investigated the effect of EM on intrapulmonary influx of
      neutrophils by intratracheal injection of lipopolysaccharide (LPS), and the
      following results were obtained. 1) The intrapulmonary influx of neutrophils was
      significantly suppressed (p less than 0.001) in mice intraperitoneally injected
      with EM at 5 mg per animal 2 hr before intratracheal injection of LPS (control
      group: 6.5 +/- 0.8 x 10(5) vs EM-treated group: 1.7 +/- 0.3 x 10(5)), but not 10
      hr before lung challenge. This inhibition was observed at 6 hr after lung
      challenge, and became maximum with 84% suppression at 24 hr. 2) The
      intrapulmonary influx of neutrophils was not affected when EM was injected
      intraperitoneally daily for 3, 7, or 14 days, and lung challenge was performed 24
      hr after the final administration of EM. 3) The number of neutrophils in the
      peripheral blood was not affected by EM. These results suggest that EM treatment
      impairs the capacity for pulmonary inflammation by reducing, at least in part,
      the migration of neutrophils to inflammatory sites.

PMID- 1402081
TI  - [Spotted fever group rickettsiosis in Chiba Prefecture].
AB  - In Chiba Prefecture, the first patient of infection with spotted fever group
      Rickettsia was found in 1987, thereafter nine patients were detected
      serologically by the end of 1990. Patients were found in the villages of
      Amatsukominato, Katsuura and Ootaki, which were located in southern part of Chiba
      Prefecture. The illness occurred from June to October. On the other hand,
      patients with Rickettsia tsutsugamushi were seen from October to September.
      Difference of prevalent seasons of these two types of rickettsiosis is important
      to make a clinical diagnosis and serological identification of this spotted fever
      group rickettsiosis. Antibody of the patients showed the highest titer to YH
      strain of Rickettsia and showed high cross-reactivity to other spotted fever
      group rickettsiae. For the diagnosis of the patient serologically, it was
      confirmed that any strain of spotted fever group Rickettsia were useful.

PMID- 1402082
TI  - [Evaluation of aerosol therapy of streptomycin for tracheobronchial and pulmonary
      tuberculosis].
AB  - The clinical features of tracheobronchial tuberculosis are distinct from those of
      pulmonary tuberculosis in some aspects. Streptomycin (SM) is claimed by some
      investigators that it has a tendency to promote the development of bronchial
      stenosis due to scarred healing of the involved endobronchial mucosa, and, for
      that reason, they recommend not to use it in treatment of bronchial tuberculosis.
      In some patients with pulmonary tuberculosis, who have renal or hearing
      disturbance, SM avoided. Yet unless SM is used improvement of tuberculosis could
      be delayed. It is the purpose of the present investigation to point out that
      aerosol therapy of SM is useful for patients with respiratory tuberculosis.
      Furthermore, we wish to demonstrate that we can safely treat the patients with
      respiratory tuberculosis who suffer from renal function or hearing disorder by
      use of aerosol therapy of SM. Prior to clinical application of the inhalation
      therapy, we confirmed that the therapy was not harmful. Serum concentration of
      SM, when inhaled, was measured in 9 volunteers. Before and after administration
      of SM aerosol, spirograms were examined in 4 volunteers, nevertheless, no special
      abnormality was recognized. It seemed that serum concentration of SM after the
      administration was two low to evoke adverse reactions (less than 3.0 gamma). In 6
      patients with pulmonary tuberculosis, blood gases were measured and no obvious
      change was observed. As a result, it was demonstrated that the endobronchial
      tuberculous lesions improved faster when treated by inhalation of aerosolized SM
      as compared with the conventional injection therapy, without evoking any apparent
      adverse reactions. In some of the patients with pulmonary tuberculosis, it seemed
      that the therapy was useful.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402083
TI  - [Asporogenic anaerobic thoracic empyema--an experimental model for anaerobic
      thoracic empyema in rabbits].
AB  - Sterile pleural effusion was induced by intrapleural administration of
      turpentine, and empyema was induced by direct intrapleural inoculation of
      bacteria in rabbits. Experimental models of anaerobic thoracic empyema were
      successfully made in this study, using Escherichia coli, Peptostreptococcus
      asaccharolyticus, Bacteroides fragilis, using the following methods; (1) a single
      bacterium inoculation of, a) E. coli, b) P. asaccharolyticus, c) B. fragilis, (2)
      simultaneous inoculations with an aerobe and an anaerobe, a) E. coli + P.
      asaccharolyticus, b) E. coli + B. fragilis. (3) an anaerobic inoculation 5 days
      after an aerobic inoculation, a) P. asaccharolyticus inoculation 5 days after E.
      coli inoculation, b) B. fragilis inoculation 5 days after E. coli inoculation.
      The developments of several parameters (sialic acid levels, glucose levels,
      oxidation-reduction potential levels, bacterial counts and WBC counts in the
      pleural fluid and so on) were measured in each group. There was little difference
      of the rate of incidence of empyema between each group. Empyema was highly
      induced even by a single anaerobe inoculation. The following tendencies were
      observed in development of parameters: (1) sialic acid levels and oxidation
      reduction potential levels were decreased only in the conditions being associated
      by B. fragilis infections. (2) in mixed infections of E. coli and anaerobes,
      bacterial counts of E. coli increased in number in the late phases of the
      infections probably by the influences of anaerobes. The experiments of groups (2)
      and (3) were designed for demonstrations of biphasic infections between aerobes
      and anaerobes, but it turned out that quite unexpected results were seen in these
      models.

PMID- 1402084
TI  - [Clinicobacteriological study of Pasteurella multocida as a zoonosis (1).
      Condition of dog and cat carriers of Pasteurella, and the influence for human
      carrier rate by kiss with the pets].
AB  - Pasteurella multocida is a gram-negative short rod-shaped bacteria, which is a
      part of the indigenous flora of the oral cavity of many animals other than man.
      The number of reports on cases of infections with this bacterium due to animal
      bites and/or scratches, bacterial infections of the respiratory tract, sepsis due
      to this organism and death caused by the bacteria have been increasing in recent
      years. We investigated P. multocida in the hair and oral cavity of 3 dogs and 29
      cats according to the classification of Mutters et al.. We also studied the
      relationship between the carrier rate for Pasteurella in the oral cavity and
      kissing of pets in 24 pet owners (3 dogs and 11 cats). No P. multocida was
      isolated from the hair of neither dogs nor cats. One strain of P. multocida
      subsp. multocida and two strains of P. stomatis, were isolated from the oral
      cavity of dogs, and 35 strains of Pasteurella were isolated from the oral cavity
      of cats. Two strains of P. multocida subsp. multocida, whose biochemical
      properties were different, were detected in the oral cavity of one cat. In three
      cats, Pasteurella other than P. multocida subsp. multocida was isolated from the
      same oral cavity. No Pasteurella was detected in the oral cavity of 19 pet owners
      who had not kissed their cats, whereas P. stomatis was isolated from the oral
      cavity of one of 2 pet owners who had kissed their cats and in 2 of 3 pet owners
      who had kissed their dogs (the same bacteria was isolated from a dog that was
      being kept by some of these positive pet owners).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402085
TI  - [Detection of polymeric IgA antibody to herpes simplex virus by pretreatment of
      sera with Streptococcus pyogenes--its application to diagnosis of primary
      infection].
AB  - In 17 patients of genital herpes virus infections, herpes simplex virus (HSV)
      specific IgA antibody responses were analyzed using an enzyme-linked
      immunosorbent assay (ELISA) and the absorption of sera with Streptococcus
      pyogenes, AW43 and AR1, which bind monomeric IgA (m-IgA) and IgG antibodies,
      respectively. The ratio of polymeric IgA (p-IgA) to total IgA was calculated from
      the formula, the p-IgA index = IgA activity after absorption/IgA activity before
      absorption. In early-convalescent-phase sera from primary cases, the p-IgA
      indices were 0.5-0.9, whereas in recurrent or provoked cases, they were lower
      than 0.2. There results indicate that the p-IgA index may be useful for rapid and
      simple differentiation of primary from non-primary HSV infections.

PMID- 1402086
TI  - [The first report of human chronic sinusitis by Pasteurella multocida subsp.
      multocida in Japan].
AB  - A 53-year-old male visited our hospital due to nasal obstruction persisting for 6
      months and constant rhinorrhea. Pasteurella multocida subsp. multocida was
      isolated from his nasal discharge and lavage fluid of the maxillary sinus, and
      also from the oral cavity of the dog he kept. The bacterial strains isolated from
      the patient and dog were identical in terms of biochemical properties, and drug
      sensitivity. Although serotype was different, the strain from the patient showed
      (A:6) and that from his dog showed (A:5). The microorganism is not present in the
      general environment. The patient had contact with his dog such as he kissed it
      frequently, gave it food with his chopsticks et al.. From the mouth of the people
      who kiss one's dog, we detected Pasteurella of the same character of bacteria as
      from the mouth of the dog. We detected two Pasteurella multocida of different
      character from only one mouth of a cat. Pasteurella multocida was checked in only
      one colony for sero type. Sero type A is the popular type for dogs and cats. The
      above suggest that their was a high possibility that the Pasteurella multocida
      subsp. multocida found in the patient was from his dog. In Japan, the incidence
      of Pasteurella multocida subsp. multocida infection has been increasing. In 1969,
      the Japanese Ministry of Health and Welfare officially communicated this
      infection as a zoonosis to related institutions. At both medical and surgical
      departments, wither the patient keeps a pet should be confirmed during interview,
      and guidance of pet keeping methods is important in some cases from the aspect of
      clinical bacteriology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402087
TI  - [Detection of Neisseria gonorrhoeae from male patients with urethritis by
      polymerase chain reaction].
AB  - A polymerase chain reaction (PCR) procedure was developed for detection of
      Neisseria gonorrhoeae. Two oligonucleotides based on sequences within a 16S
      ribosomal RNA gene from N. gonorrhoeae were used as extension primers for the
      PCR. A single DNA fragment of 206 bp was amplified, when N. gonorrhoeae DNA was
      template for the PCR. No amplified product was detected in Chlamydia trachomatis
      DNA, Ureaplasma urealyticum DNA or other bacterial DNAs. The DNA fragment of 206
      bp was detected on agarose gel electrophoresis, when DNA of greater than or equal
      to 6.5 N. gonorrhoeae per PCR was used as template DNA for the PCR. The culture
      and the PCR were carried out for detection of N. gonorrhoeae in 67 urethral swabs
      obtained from male patients with urethritis. In 27 of 28 specimens in which N.
      gonorrhoeae was isolated and identified by the culture, 206 bp DNA fragment was
      amplified by the PCR, but in one specimen no DNA fragment was detected. In 2 of
      39 culture-negative specimens, 206 pb DNA fragment was detected and in the
      remaining specimens, PCR was negative for N. gonorrhoeae. The overall detection
      coincidence rate between the culture and the PCR was 95.5% (64/67). Thus, the PCR
      procedure developed in this study was sensitive and specific for detection of N.
      gonorrhoeae and could be applied for diagnosis of gonococcal urethritis.

PMID- 1402088
TI  - [The long-term chemotherapy with erythromycin (EM) in chronic lower respiratory
      tract infections--third report: clinical study of cases administered EM over 3
      years].
AB  - An investigation was made of the use of EM therapy which began in 1986 or earlier
      in 31 cases with chronic lower respiratory tract infections. 1) Of the 20 cases
      in which EM (Erythromycin stearate) administration (600-1200 mg/day) was
      continued for 3 years or more and its usefulness could be evaluated, treatment
      with this agent was judged markedly effective in three, effective in 14, somewhat
      effective in two, and ineffective in one. This amounted to an effectiveness rate
      (effective or better) of 85%. 2) Improved QOL was observed in 15 of the 20 cases.
      3) In the Pseudomonas infected cases, a discrepancy was seen between the
      effectiveness rate of 87.5% and the disappearance rate of the organism (12.5%),
      while in the Haemophilus cases no such discrepancy was found (75%). 4) EM
      administration was stopped in 11 cases because of side effects in two
      (stomatitis, gastrointestinal disorder) death in five, desire of the patient in
      three, and transfer to another hospital in one. The cause of death cases had no
      connection with administration of EM. 5) In the three patients who stopped EM on
      their own, the agent was again administered because of exacerbation of symptoms,
      although this readministration proved ineffective in two of the cases. The above
      results suggest that long term EM therapy is useful and that its continued
      administration is important.

PMID- 1402089
TI  - [The role of TNF in septic ARDS].
AB  - This study was performed to demonstrate the role of TNF in septic ARDS. The
      interaction with neutrophil and TNF was examined in both in vitro and in rat
      experimental observation. The results obtained are as follows: Serum level of
      natural TNF was significantly increased immediately after the endotoxin injection
      into the rat vein. In in vitro observation, TNF activated neutrophil and enhanced
      super oxide production and elastase was released from neutrophil. On the other
      hand, TNF was inactivated by contact with elastase released from activated PMNs
      both in dose and in time dependently. Also, in the in vivo study, the serum level
      of natural TNF that was enhanced by endotoxin injection was continued for a
      longer period in neutropenic rats than in the normal rat. The lung tissue injury
      such as cell infiltration, capillary congestion and increased intrapulmonary
      fluid in morphometric determination were observed only when the extremely high
      dose of TNF was injected. These findings were more significantly observed in the
      neutropenic rats than in the normal neutrophil rat. The weaker interaction of
      PMNs elastase to TNF is suspected in such neutropenic animals. From the above,
      the role of TNF in septic ARDS may be explained as follows: By endotoxin
      injection, TNF is released from stimulated macrophages. The released TNF
      activates neutrophil which plays the main role of septic ARDS. In the usual
      system, lung tissue damage induced by TNF is inhibited, because TNF is
      inactivated by elastase released from activated PMNs. However, in neutropenic
      state, PMNs elastase is not enough to inhibit the TNF action, then the tissue
      damage is directly induced by TNF. As my conclusion, the role of TNF in septic
      ARDS is to provide two different ways by the host is condition. One is to
      activate neutrophils in the usual condition and the another is to introduce
      direct damage of lung tissue in the neutropenic state.

PMID- 1402090
TI  - [An effective concentration method for human immunodeficiency virus type 1 (HIV
      1)].
AB  - We designed an effective virus concentration method to prevent the infection with
      human immunodeficiency virus type 1 (HIV-1) in laboratories. The absorbent of
      Minicon concentrators (Amicon Division, M.R. Grace & Co.-Conn.) was changed to
      chitin, a mucopolysaccharide extracted from the shells of Japanese pink crab. HIV
      1 in the supernatant of HIV-1 infected Molt-4 cells was concentrated by Minicon
      and the new concentrators. The new concentrator showed good concentration rate
      and equality of concentration speed.

PMID- 1402091
TI  - [Relation of bacterial flora between upper and lower respiratory tracts in
      patients with long-term tracheostomy].
AB  - Throat secretions (TS) and bronchial secretions aspirated from tracheostomy
      (TSTA) were cultured at the same time in 9 subjects with long term tracheostomy
      every two weeks from January, 1990 to December, 1990. Total number of each
      examination in TS and TSTA were 200 times. Mean number of bacteria isolated by
      single culture were 2.9 strains in TS and 1.8 strains in TSTA. Isolated bacteria
      were mainly alpha-Streptococcus (84.8%) and Neisseria (69%) in TS, and
      Pseudomonas aeruginosa (53.5%) and Serratia marcescens (30%) in TSTA. Only 20% of
      P. aeruginosa or S. marcescens in TSTA were isolated from TS. In 8 cases of 9, P.
      aeruginosa in TSTA were isolated with every time or long term. There were 14
      episodes of respiratory infections in 6 cases. P. aeruginosa were causative
      organisms in 7 episodes. It suggests that P. aeruginosa tended to colonize in
      lower respiratory tracts of the patients with long term tracheostomy and to
      become causative organisms in respiratory infections.

PMID- 1402092
TI  - [Protective activity of tea and catechins against Bordetella pertussis].
AB  - We examined the bactericidal activity of tea and catechins against Bordetella
      pertussis. Green tea, black tea and coffee showed marked bactericidal activity at
      their concentrations in beverages, while pu-erh tea killed the bacteria in a
      moderate way. (-) Epigallocatechin gallate (EGCg) and theaflavin digallate (TF3)
      showed also marked bactericidal activity. Green tea and black tea also
      effectively blocked the adhesion of B. pertussis to HeLa and CHO cells, whereas
      ECGg and TF3 could not. EGCg and TF3 markedly inactivated leuco-lymphocytosis
      promoting activity of pertussis toxin. Black tea showed slight but significant
      inactivation of the activity, whereas green tea showed no inactivation. These
      results suggest that green tea, black tea, EGCg and TF3 might act as prophylactic
      agents against pertussis infection.

PMID- 1402093
TI  - [Antimicrobial and microbicidal activities of tea and catechins against
      Mycoplasma].
AB  - We examined tea extracts, (-) epigallocatechin gallate (EGCg) and theaflavin
      digallate (TF3) for their antimicrobial and microbicidal activities against
      Mycoplasma. Green tea and black tea showed antimicrobial activities against M.
      pneumoniae. At a concentration of 0.2% green tea and black tea showed
      microbicidal activities against M. pneumoniae and M. orale but not against M.
      salivarium. Extracts of pu-erh tea showed a slight microbicidal activity against
      M. pneumoniae and M. orale. EGCg purified from green tea and TF3 from black tea
      markedly showed microbicidal activities against M. pneumoniae. M. orale and M.
      salivarium. These results suggest that tea and catechins can be used as
      prophylactic agents against Mycoplasma pneumoniae infection.

PMID- 1402094
TI  - [Analysis of 84 cases with fungemia].
AB  - Eighty-four patients with fungemia were analyzed. Fungi had been isolated by
      culture of blood samples, including blood from the catheter for intravenous
      hyperalimentation, between 1986-1990. Candida albicans (39.3%), Candida
      parapsilosis (20.2%), Candida tropicalis (11.9%), Candida glabrata (10.7%),
      Candida guilliermondii (4.8%) and Trichosporon beigelii (4.8%) were the most
      frequently isolated fungal pathogens. Four patients' blood yielded two different
      fungal species. Fifty-nine cases were male, and 25 cases were female. Forty-six
      of the 84 patients died (54.8%), but there were no differences in the overall
      mortality rate as a function of the fungal species or sex. All patients had
      underlying diseases: solid cancer, 37 cases; cardiovascular diseases, 9 cases;
      gastrointestinal diseases excluding gastrointestinal cancer, 8 cases; central
      nervous system diseases, 7 cases; premature infants and congenital abnormality, 7
      cases; leukemia, 6 cases and miscellaneous, 10 cases. Twenty-four of the 46 dead
      cases were autopsied, and eight cases showed systemic fungal lesions. However, in
      one case of pulmonary cryptococcosis and one case of pulmonary penicilliosis,
      there was no correlation between the isolation of C. glabrata by blood culture
      and the pathological findings. A fungus-positive blood culture was surmised to be
      a result of contamination of the sample in 33 cases, and the mortality rate for
      those cases was 72.2% (24 cases). For 6 of the corpses, fungal lesions observed
      at autopsy were compatible with the types of lesions found by the fungi which had
      been isolated before death. Removal of the catheter reduced the mortality rate to
      41.7%. Fungal endophthalmitis was diagnosed in six cases.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 1402095
TI  - [A clinical study of bacteremia in the last fifteen years].
AB  - Between 1976 and 1990, 208 cases of bacteremia in our department were studied.
      Community acquired bacteremias were only 18 (8.7%) cases. Bacteremias,
      particularly caused by Gram positive organisms, increased significantly after
      1981, compared with the first five years. It was related to the marked increase
      in cases of venous access devices and less sensitivity of the Gram positive
      organisms to the new cephem antibiotics. In the study, 144 (69.2%) cases were
      eradicated. Severe underlying diseases or complication of pneumonia influenced
      the eradication rate of bacteremia. Bacteremia caused by methicillin resistant
      Staphylococcus aureus or Pseudomonas aeruginosa showed poor prognosis. The
      average duration from onset to death, was 5.1 days. Forty cases (62.5%) died
      within 3 days. Among the 201 cases, leukocytosis (WBC greater than 10,000/mm3)
      was present in 38.3%, while leukopenia (WBC less than 1000/mm3) in 25.3%.
      Eradication rate between the two groups was not significant. CRP was elevated
      (greater than 8.5 mg/dl) in 63.5%. The prognosis of this group was significantly
      poor. Elevation of serum bilirubin was also related with increase of mortality.
      According to these results, empiric therapy before the isolation of organisms is
      the most important strategy for treatment of bacteremia.

PMID- 1402096
TI  - [Studies on motile-Aeromonas infection 3). Phage typing of motile Aeromonas
      isolated from patients with diarrhea].
AB  - Phage types were determined for 102 strains of motile Aeromonas isolated from
      patients with diarrhea at four metropolitan hospitals in Tokyo. The following
      results were obtained. 1) Of the 102 strains examined, 52 (51.0%) were divided
      into 28 phage types. This rate was considerably higher, compared to our previous
      results, namely, 21.7% for strains isolated from natural environments and 25% for
      those isolated from meats. By bacterial species, phage types could be determined
      for 33 (52.4%) of 63 strains of A. hydrophila, for 16 (45.7%) of 35 strains of A.
      sobria, 2 (50.0%) of 4 strains of A. caviae and 1 (100%) strain of Aeromonas spp.
      2) Of the 52 strains for which the phage types could be determined, the greatest
      number (16 strains, 30.8%) were identified as belonging to Type I group. These
      are followed by 5 strains (9.6%) which were identified as Type I/III group and 2
      strains (3.4%) each identified as Type I/II, I/II/V, IV, V and VI groups. The
      remaining 21 strains were identified as belonging to one of the other phage type
      groups. Thirty-five (67.3%) of the strains for which the phage types were
      identified, were found to belong either to Type I group or to combinations with
      Type I. This demonstrated that 34.0% of the isolates from patients with diarrhea
      were related to Type I.

PMID- 1402097
TI  - [Morphology and immunotyping of AC-43 strain of Chlamydia pneumoniae isolated
      from a Japanese child].
AB  - A strain of Chlamydia pneumoniae (C. pneumoniae) which had been isolated from a
      Japanese child (AC-43) was examined morphologically and serologically using micro
      immunofluorescent (micro-IF) test. Inclusions of AC-43 were stained by an
      indirect immunofluorescent method using C. pneumoniae specific monoclonal
      antibody. They were dense round inclusions which had been reported as a
      characteristic figure for C. pneumoniae. An elementary body (EB) of AC-43 was
      pear-shaped by electron micrograph, which was the same as previous reports for C.
      pneumoniae. We produced monoclonal antibodies using purified EB of AC-43 as
      antigen. Culture fluids of these clones reacted with C. pneumoniae antigens, but
      did not react with C. trachomatis or C. psittaci antigens by micro-IF tests.
      There was no difference in morphological and serological findings among standard
      strains and Japanese isolate of C. pneumoniae.

PMID- 1402098
TI  - [Isolation of Chlamydia pneumoniae from a patient with acute bronchitis].
AB  - Chlamydia was isolated from the throat of a 15-year-old male patient with acute
      bronchitis. The Chlamydia isolate, YK-41, was stained with FITC-conjugated
      monoclonal antibodies specific to C. pneumoniae and the genus Chlamydia, whereas
      staining of monoclonal antibody specific to C. trachomatis was negative. These
      results indicated that the strain YK-41 could be identified as C. pneumoniae.
      Serum IgM antibody against C. pneumoniae was detected in high titer in the
      patient in the acute phase using the microimmunofluorescence (MIF) test, serum
      IgG antibody against C. pneumoniae demonstrated a fourfold antibody titer rise
      between acute and convalescent serum using MIF test. Thus, our patient almost
      certainly contracted acute bronchitis caused by C. pneumoniae.

PMID- 1402099
TI  - [A case of empyema with subphrenic abscess].
AB  - A 75-year-old female was admitted to our hospital with complaints of fever, cough
      and left hypochondralgia. She had been operated for cholecystectomy ten years
      ago. Chest roentgenogram indicated bilateral pleural effusion. Tube drainage was
      done to the left thorax and empyema was caused by Bacteroides fragilis and
      Escherichia coli (E. coli). Though antibiotic therapy was already being
      conducted, the left hypochondralgia persisted. A CT scan and MRI demonstrated
      local subphrenic abscess around the spleen due to E. coli. Tube drainage was
      conducted to the subphrenic abscess under ultrasound control and and the symptoms
      disappeared rapidly. The present results show that examination of the abdomen is
      necessary for empyema with complication of compromised host. The past history of
      abdominal surgery and disturbance in the biliary tract should also be considered.

PMID- 1402100
TI  - [A case of mediastinitis and bilateral pyothorax, following acute epiglottitis
      with concurrent Aspergillus infection].
AB  - Life threatening mediastinitis as a complication of acute epiglottitis is very
      rare. A 38-year-old male in previously good health was admitted to our hospital
      in a state of unconsciousness. Seven days prior to admission he had complained of
      a sore throat, dysphagia, high fever and dyspnea. A chest X-ray on admission
      showed widening of the mediastinum, mediastinal emphysema, subcutaneous emphysema
      and left pleural effusion. Bronchoscopy showed the swelling of supraglottic
      structures. He was diagnosed as having acute mediastinitis and pyothorax as a
      complication of acute epiglottitis, but pathogens were not identified. The blood
      was hyperglycemic and insulin therapy was started. Though he gradually improved
      by massive antibiotic therapy, steroid therapy, tracheotomy and surgical drainage
      of both the left thoracic cavity and the mediastinum, he died suddenly of massive
      hemoptysis. Autopsy revealed that the acute mediastinitis had healed, but that
      the Aspergillus infection was present in both lungs and the pericardium. The
      Aspergillus infection was not lethal in the present case, and it seemed that
      death had resulted from arterial hemorrhage caused by erosion of the trachea. The
      present case suggests the need for antifungal therapy even in non
      immunocompromised patients in particular when massive doses of antibiotics and
      steroids are administered.

PMID- 1402101
TI  - [A case of Vibrio cholerae non-O1 septicemia with liver cirrhosis].
AB  - A case of Vibrio cholerae non-O1 septicemia is described in this paper. A 45-year
      old male with a three year history of liver cirrhosis, was admitted to our
      division with hematemesis, abdominal pain, high fever and a loss of
      consciousness. Three days before onset of symptoms, he traveled to Ishigaki
      Island and ate a raw lobster. Two days after, his temperature rose to 39.7
      degrees C and the blood pressure dropped to 36/- mmHg. By endoscopic examination,
      an ulcer was found in the stomach, and the bleeding was stopped by electrical
      coagulation. Blood culture showed growth of V. cholerae non-O1. The organism was
      found to be sensitive to OFLX, CZX, MINO, LMOX and CP. Although DIC, infections
      of fungus and MRSA occurred as complications, he recovered by adequate
      procedures. Subsequently, he left this division after eight weeks. There are
      various reports related to V. cholerae non-O1 septicemia in foreign countries,
      but few cases have been reported in Japan. And these cases had severe underlying
      diseases such as leukemia and liver cirrhosis.

PMID- 1402102
TI  - [A case of diffuse panbronchiolitis relieved rapidly by the treatment of
      roxithromycin].

PMID- 1402103
TI  - [Characterization of Rickettsia tsutsugamushi strains newly isolated in Ehime
      Prefecture, Japan].
AB  - Five strains of Rickettsia tsutsugamushi were isolated in Ehime Prefecture during
      December 1987 to January 1990. Of these, two strains, the Yamazaki and Noma-3,
      were isolated at Noma area of Imabari city and three strains, the Kakiwara-10, 
      11, -12, at Kakiwara area of Uwajima city. The Yamazaki strain was isolated from
      a patient of tsutsugamushi disease and the other strains from wild rodents
      (Apodemus speciosus). These strains showed virulence in euthymic mice. The
      calculated LD50 of the Yamazaki and Kakiwara-10 strains showed 10(-3.0) and 10(
      1.8), respectively. The immunofluorescent antibody test using thirty monoclonal
      antibodies to six representative strains, the Gilliam, Karp, Kato, Irie, Hirano
      and Shimokoshi, revealed that two strains isolated at Noma area, the Yamazaki and
      Noma-3, were identified as the Karp type and three strains at Kakiwara area, the
      Kakiwara-10, -11, -12, were identified as the Kato type. It was clarified that
      the serotypic differences were present among the strains isolated in Ehime
      Prefecture. Moreover, these five strains isolated in Ehime Prefecture did not
      react with the serotype-specific monoclonal antibodies to the Irie, Hirano and
      Shimokoshi strains known as the representative strains of so-called new type of
      tsutsugamushi disease, showing antigenic differences.

PMID- 1402104
TI  - Changing patterns of blood culture isolates from patients with acute leukemia: a
      review of twenty years' experience.
AB  - During the 20-year period, 1972-1991, 286 episodes of bacteremia occurred in 200
      (45%) of 445 patients with acute leukemia in a hematology ward, giving an
      incidence of 482 episodes per 1,000 hospital admissions. The frequency of
      bacteremia was almost unchanged throughout the study period. The frequency of
      gram-negative bacilli decreased significantly, however, from 81% of all the
      isolates for the first half of the study period to 50% for the latter half.
      Despite the common use of ceftazidime and imipenem during the last 5-year period,
      Pseudomonas aeruginosa increased in frequency to be the most frequent organism.
      This was opposite to the decreased frequencies of Escherichia coli, Klebsiella
      pneumoniae and Enterobacter cloacae. The isolates of P. aeruginosa obtained
      during this period, all of which proved sensitive to ceftazidime and/or imipenem,
      were almost equally distributed among five serogroups, although a temporal
      preponderance of a limited number of serogroups was observed during the preceding
      15-year period. On the other hand, the frequency of gram-positive cocci increased
      from 9% in the first decade to 35% in the latter decade. Staphylococcus
      epidermidis, Enterococcus species and, to a lesser extent, Staphylococcus aureus
      were ranked as major pathogens. Among the recent isolates of S. aureus,
      methicillin-resistant strains virtually replaced methicillin-sensitive ones.
      Therefore, until more effective means for control of P. aeruginosa bacteremia in
      particular become available, the occurrence of this infection will continue to
      limit the successful treatment of acute leukemia.

PMID- 1402105
TI  - [Limulus test (factor G) and polysaccharides from fungus].
AB  - Picogram quantifies per ml of endotoxin showed a positive limulus test. The
      concentration more than ten pg/ml of curdlan ((1-3)-beta-D-glucan) was also
      positive to a conventional limulus test, which contains a factor G. One nanogram
      per ml of CM-curdlan was positive, but higher concentration of 10 pg/ml of CM
      curdlan decreased its optical density of the conventional limulus test. More than
      one hundred ng/ml of mannan from Saccharomyces cerevisiae did not react with
      factor G. However, a culture supernatant of Saccharomyces cerevisiae activated
      factor G. This result suggested that beta-glucan activated factor G. In addition,
      culture supernatant of Aspergillus fumigatus, Rhodotorula rubra, Candida
      parapsilosis, Candida tropicalis, Candida krusei also activated factor G, but
      Cryptococcus neoformans did not activate it.

PMID- 1402106
TI  - [Comparison of sensitivity of Hep-2 cells with that of HL cells against Chlamydia
      pneumoniae].
AB  - We compared the growth of Chlamydia pneumoniae, reference strain TW183 and an
      isolate from a Japanese infant, AC43 in HeLa229, HL and Hep-2 cells. The mean
      number of inclusion-forming units was significantly higher on HL cells than
      HeLa229 cells, when the cells were not pretreated with DEAE-dextran. When the
      cells were not pretreated with DEAE-dextran, Hep-2 cells had a higher mean number
      of inclusion-forming units and a higher yield than other cell lines. Iscove's
      modified Dulbecco medium enhanced growth of strain TW183 in HeLa229 cells but had
      a low yield of strain AC43 in Hep-2 cells.

PMID- 1402107
TI  - [Clinical studies on pediatric purulent meningitis--clinical symptoms and
      prognosis].
AB  - In 149 patients with purulent meningitis we encountered in the period of 20 years
      from 1970 to 1990, their clinical symptoms and prognosis were investigated. Death
      or sequela was noted in many of the patients having loss of consciousness,
      stiffness of the members and/or cyanosis as primary clinical symptoms, or having
      hypoalbuminemia (less than 2.5 g/dl) and/or thrombocytopenia as abnormal
      laboratory findings, or having excessive protein levels and/or excessively low
      sugar levels in cerebro-spinal fluid. Early initiation of adequate antibiotic
      therapy, as well as symptomatic treatment using transfusion, steroids and
      anticonvulsants, are important.

PMID- 1402108
TI  - [Clinical studies on pediatric purulent meningitis--statistical analysis of
      etiology and therapy].
AB  - In a total of 149 children with purulent meningitis we encountered in our
      institute in the last 20 years, the causatives, the changes in therapeutic
      management and the prognosis were investigated. The causatives could be detected
      in 109 patients (73%): H. influenzae; 30 patients (20%), S. pneumoniae; 18
      patients (12%), E. coli; 13 patients (9%), GBS; 7 patients (5%) and S. aureus; 6
      patients (4%). These five causatives were detected in 49% of the total patients,
      or 67% of the patients in whom causatives could be detected. Of these five
      causatives, E. coli were detected the most frequently in the first half of
      1970's, but, in recent years, the detection of GBS, S. pneumoniae and H.
      influenzae has been remarkably increasing. In spite of progress in antibiotics,
      the prognosis of the disease due to S. pneumoniae, GBS and S. aureus was poor. In
      the majority of the patients who died, the death came within five days after
      hospitalization due to loss of consciousness, convulsion etc. It is therefore
      necessary not only to initiate strong antibiotic treatment as soon as possible
      after early diagnosis, but also to take symptomatic measures such as steroidal
      treatment, treatment of shock etc.

PMID- 1402109
TI  - [Role of capsular polysaccharide and lipopolysaccharide of Klebsiella pneumoniae
      in experimental mice pneumonia model].
AB  - In this study, role of capsular polysaccharide (CPS) and lipopolysaccharide (LPS)
      of Klebsiella pneumoniae was investigated in experimental mice pneumonia model.
      Inoculation with K. pneumoniae mucoid strain DT-S into mice lung induced
      expansive, voluminous lethal pneumonia characterized with thickening of the
      alveolar septa caused by infiltration of inflammatory cell and packing of
      bacteria within alveolar spaces. On the other hand, mice lung inoculated with K.
      pneumoniae DT-X, which was non-mucoid mutant isolated from DT-S during natural
      passage, showed infiltration of inflammatory cell into alveolar spaces but there
      was no death of mice during the course of this pneumonia. Inoculation of CPS 100
      micrograms of DT-S strain into mice lung induced lesser extent of accumulation of
      inflammatory cell than that of LPS 4 micrograms of this strain. Stimulation of
      alveolar and peritoneal macrophage with CPS, even at a concentration of 100
      micrograms/ml, induced weaker Interleukin-1 (IL-1) activity than stimulation with
      LPS 4 micrograms/ml. These results suggest that since CPS of K. pneumoniae DT-S
      encapsulate bacteria including LPS, CPS may inhibit chemotaxis of inflammatory
      cell and IL-1 production of macrophage to be induced by LPS during course of
      pneumonia. It is speculated that existence of CPS have important role in
      modulating host response to bacterial LPS, and this effect of CPS may be related
      with difference of pathological findings of lung and lethality between K.
      pneumoniae DT-S and DT-X.

PMID- 1402110
TI  - [Studies on the giardiasis as the zoonosis. III. Prevalence of Giardia among the
      dogs and the owners in Japan].
AB  - To obtain the basic data on the route of Giardia infection as zoonosis, of many
      regions in Japan, the feces from 2218 dogs were examined for detection of Giardia
      cysts. Giardia cysts were detected in 239 of the 2218 dogs (10.9%), which was the
      same as previous reports from America. None were found from the owners of 51 dogs
      in which Giardia cysts were detected. The detection rates of each facilities
      were, 68 of 366 (18.6%) from the breeder's kennels, 169 of 1811 (9.3%) in
      individual houses, 2 of 42 (4.9%) from research institutes. The detection rate of
      the breeder's kennels was higher than the other two facilities (p less than 0.05,
      p less than 0.001). The detection rates of Kanagawa and Shizuoka prefectures
      among 17 regions in Japan were higher than the others (p less than 0.001, p less
      than 0.05). Especially in Shizuoka, the rate of the individual houses was higher
      than from breeder's kennels. In kanagawa the rates of the individual houses and
      the breeders kennels were higher than the mean in Japan (p less than 0.001).
      Therefore one must instruct the breeders when teaching health education to
      included zoonosis, and that the detection rate of the age groups of less than 3
      years old was high-221 of 1276 (17.3%). Since the detection rates of Giardia
      cysts in the dogs were low, the possibility that human infection acquired from
      dogs was low. However, some of patients with giardiasis we encountered had never
      been abroad, and it is not yet clear whether Giardia is strictly host specific or
      not, so attention should be paid to the possibility of cross-infection between
      man and animals.

PMID- 1402111
TI  - [Studies on genetic differentiation of Salmonella enteritidis isolates by plasmid
      profile].
AB  - Since 1989, the number of salmonellosis cases caused by S. Enteritidis has
      increased considerably in Japan. Genetic differentiation of 385 strains isolated
      from January 1982 to December 1988 and January 1989 to April 1991 were used for
      plasmid profiles. Plasmids were found in 377 out of 385 strains; therefore, only
      8 strains carried no plasmid. Among 377 strains, 15 different plasmid profile
      types (OP-1 to OP-15) were classified. The most common plasmid profile types from
      1982 to 1988 were OP-7 (70 kbp) and OP-8 (70 kbp and 2 kbp). On the other hand,
      the most common plasmid profile types from 1989 to 1991 were OP-1 (60 kbp) and OP
      2 (60 kbp and 54 kbp). Serovar-specific virulence 60 kbp plasmids of S.
      Enteritidis were identified in 7 plasmid profile types (A total of 200 strains).
      In the other plasmid profile types, 70 kbp plasmids were found in 5 plasmid
      profile types (A total of 173 strains). In restriction enzyme analysis of 70 kbp
      plasmid DNAs obtained from 5 plasmid profile types of S. Enteritidis, we found
      that these plasmid DNAs shared both 60 kbp and 10 kbp fragments. These results
      indicate that these plasmid profile types also carried serovar-specific virulence
      plasmids of S. Enteritidis. The strains of plasmid profile type OP-2 were SA
      (sulfisoxazole) and SM (streptomycin) resistance, and the 54 kbp plasmids in the
      strains of OP-2 were transferred by bacterial conjugation into the E. coli
      strains. All transconjugants acquired SM resistance.

PMID- 1402112
TI  - [Microtiter enzyme-linked immunosorbent assay for rubella antibodies in human
      sera--analysis by parallel line assay method].
AB  - Antibodies against rubella virus in human sera were measured by ELISA and
      antibody titers were calculated by the parallel line assay method. The dose
      response regression curves of standard sera and test sera containing IgG antibody
      calculated by the parallel line assay method showed linearity, and were parallel
      to one another. However, the regression lines of sera positive for IgM antibody
      against rubella virus were not parallel to one another in the low dilution
      region, but parallel in the higher dilution region. A good correlation was
      observed between the rubella IgG antibody titers measured by the hemagglutination
      inhibition (HI) test and those calculated by the parallel line assay method. The
      coefficient of the correlation was 0.781. Time-course studies of IgG or IgM
      antibody titers against rubella virus in rubella patients or in vaccines with MMR
      vaccine indicated that the ELISA was more precise and specific method than the HI
      test. Thus, the parallel line assay method using ELISA is considered to be a more
      useful method for the detection and quantification of antibodies to rubella than
      the conventional HI test.

PMID- 1402113
TI  - [Detection of Legionella pneumophila using a nested polymerase chain reaction].
AB  - We evaluated the usefulness of a Nested PCR method for detecting Legionella
      pneumophila. This method resulted in L. pneumophila specific detection as far as
      we evaluated. The first and second step PCR achieved the sensitivity as small as
      10 pg and 10 fg of the target DNA, respectively. In the detection from Legionella
      seeded sputa, the method could detect 0.1 cfu/ml of the bacteria, and it took
      about 12 hours to detect the target DNA. We demonstrated that the Nested PCR
      method was superior in sensitivity and rapidity for isolation of the bacteria to
      the conventional using low pH treatment and selective media for Legionella.

PMID- 1402114
TI  - [Incidence of Mobiluncus spp. from the patients with clinical bacterial
      vaginosis].
AB  - Aerobic and anaerobic cultures as well as a Gram stain and wet mount preparations
      were made of vaginal swabs in twenty patients with clinical bacterial vaginosis.
      Mobiluncus spp. were detected in 7 cases (35%). Cultures appeared to indicate
      that mixed abnormal flora between aerobic and anaerobic bacteria are found in
      bacterial vaginosis, and that Mobiluncus spp. may play a role in bacterial
      vaginosis.

PMID- 1402115
TI  - [Evaluation of the alkaline-phosphatase labeled DNA probes for Mycobacterium
      tuberculosis and Mycobacterium avium complex].
AB  - Non-radioisotopic, alkaline phosphatase-labeled DNA (AP-DNA) probe tests for the
      identification of Mycobacterium tuberculosis complex (Mtb) and Mycobacterium
      avium complex (MAC) were evaluated. The overall agreement, sensitivity and
      specificity of the AP-DNA probes for Mtb and MAC were 100% respectively compared
      with the conventional biochemical method. Because the procedure is rapid (it can
      be completed approximately 120 min), safe (it does not use radioisotopes) and
      convenient (it does not need the special equipment to be performed), it can be
      easily performed in any clinical laboratory.

PMID- 1402116
TI  - [Long-term chemotherapy using erythromycin (EM) for chronic lower airway
      infection: effectiveness of clarithromycin in EM ineffective cases--the fourth
      report].
AB  - The effectiveness of long-term chemotherapy using Erythromycin (EM) for chronic
      lower airway infection has been practically proved. However, there still exist
      some ineffective cases, or cases in which the clinical effect was scarcely seen.
      In the present study was administered Clarithromycin (CAM) to such cases and
      found that CAM was effective in alleviating symptoms in some of them. The results
      were presented along with clinical findings and other basic studies. The subjects
      were 4 cases in which EM was either ineffective or low in its clinical effect.
      The subjects consisted of 1 case of DPB and 3 cases of bronchiectasis. EM was
      clinically ineffective in 2 cases and slightly effective in the two others. The
      pathogen was Pseudomonas aeruginosa in all cases. The dosage of EM was 200-1200
      mg/day. The period of administration ranged from 2 years to 6 years 9 months. CAM
      was given orally after meals at a dose of either 200 or 400 mg/day. Chemotherapy
      had continued for 3-8 months at the time of final observation (Feb. 1992).
      Clinical effectiveness was evaluated on the basis of sputum volume and PaO2
      examination, as well as evaluation by the patients themselves. As a result, in
      all 4 cases, reduction in sputum volume and improvement of PaO2 were observed.
      All subjects evaluated CAM therapy as being more effective than EM therapy.
      Moreover, it was found that CAM inhibited both the elastase and leucocidin
      produced in one of the ineffective cases by P. aeruginosa, whereas EM
      didnt.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402117
TI  - [Quantitative analyses of the normal throat flora of children with upper
      respiratory tract infections].
AB  - Relationship between the normal throat flora and pathogenic bacteria recovered
      from the throat in 139 children with upper respiratory tract infections in winter
      were studied using quantitative analyses. Pathogenic bacteria examined include S.
      pyogenes, H. influenzae, S. aureus, and S. pneumoniae, and the normal floras
      include alpha-streptococci, gamma-streptococci, Neisseria species, and
      Micrococci. Children with S. pyogenes in their throats (S. pyogenes group) were
      examined with anti-streptococcal antibodies such as anti-streptolysin O, anti
      streptokinase, and anti-deoxyribonuclease B. Eighty seven pathogenic bacteria
      were recovered from 72 children (51.8%) out of 139. S. pyogenes and S. pneumoniae
      groups showed significantly lower alpha-streptococci and gamma-streptococci in
      incidence of appearance when compared with children with the no pathogenic
      bacteria in their throats (no bacteria group). H. influenzae group showed
      significantly lower gamma-streptococci and higher Neisseria sp. in incidence of
      appearance compared with the no bacteria group. Positive cases for anti
      streptococcal antibodies showed a significantly lower alpha-streptococci in
      number compared with negative cases for antibodies and the no bacteria group, and
      a significantly lower gamma-streptococci in incidence of appearance compared with
      the no bacteria group. These data suggest that the normal throat flora may have a
      role in prevention of colonization by the pathogenic bacteria in vivo, as were
      shown in vitro by many authors, and that the quantitative analysis of the normal
      flora is useful because this methodology might reveal whether the bacteria
      recovered from the throat show the pathogenicity.

PMID- 1402118
TI  - [Plasma beta-glucan levels in deep fungal infections accompanying hematological
      diseases and clinical efficacy of miconazole--a multi-institutional study].
AB  - Miconazole (400-1200 mg/day) was administered to patients with deep mycosis and
      suspected deep mycosis, and the efficacy evaluated. beta-Glucan was determined as
      the early diagnostic parameter of deep mycosis, and the relationships between the
      clinical efficacy of miconazole and the titers of beta-glucan were also
      evaluated. Forty-nine cases were evaluated, including 2 cases of deep mycosis and
      47 cases of suspected deep mycosis. Most of the patients had hematological
      malignancies. The rate of efficacy was 100% (2/2) in deep mycosis, 66.0% (31/47)
      in suspected deep mycosis, and 67.3% (33/49) in total. beta-Glucan was determined
      in 39 cases before the administration of miconazole. The rate of beta-glucan
      positivity was 100% (1/1) in deep mycosis and 44.7% (17/38) in suspected deep
      mycosis. beta-Glucan was also determined before and after the administration of
      miconazole in 11 cases. The titers of beta-glucan became negative in 6 cases,
      decreased in 2 cases and increased in 3 cases. Thus, the beta-glucan titers
      became negative or decreased in 72.7% (8/11) of the cases. Efficacy of miconazole
      was 83.3% (5/6) in the cases in which beta-glucan became negative, 50.0% (1/2) in
      the cases in which the titers of beta-glucan decreased, and 33.3% (1/3) in the
      cases in which the titers of beta-glucan increased. Miconazole was effective in
      the treatment of deep mycosis, and the titers of beta-glucan correlated well with
      the clinical efficacy of miconazole. The determination of beta-glucan appears to
      be useful for the diagnosis of deep mycosis.

PMID- 1402119
TI  - [A case of tracho-bronchial aspergillosis complicated with acute myeloblastic
      leukemia].
AB  - A 59-year-old male was admitted to our hospital in Jan. 1991 with complaints of
      general malaise and palpitation. Laboratory findings on admission showed anemia,
      thrombocytopenia and leukopenia consisted of 2.0% myeloblasts with Auerbodies.
      The bone marrow study showed granuloid hyperplasia with 45.5% myeloblasts. The
      diagnosis of acute myeloblastic leukemia (M1) was made. After BHAC-AMP therapy,
      he obtained complete remission. However, he complained of fever and cough, and
      his chest X ray film showed a focal infiltrative shadow in the right upper lung
      field. Antibiotics for bacteria and fungus were administered and the abnormal
      shadow improved in a week. However, as he had hemosputum, the bronchoscopic
      examination was performed, and multiple ulcers covered by yellow-white tissue
      were revealed on the wall of the trachea and bilateral main bronchi. Biopsy
      specimens obtained by transbronchial biopsy showed bronchial aspergillosis.
      Though intravenous infusion and inhalation of amphotericin B were effective for
      aspergillosis, he had a relapse of the leukemia and died in autumn, 1991.

PMID- 1402120
TI  - Salmonella-associated with deep vein thrombosis: report of a case and review of
      the literature.

PMID- 1402121
TI  - [A case of Trichosporon beigelii peritonitis in CAPD].
AB  - Continuous ambulatory peritoneal dialysis (CAPD) was introduced to Japan ten
      years ago and was established as the treatment for end-stage renal disease along
      with HD. Although the incidence of peritonitis in CAPD has decreased by educating
      the patients and parents and the improvement of various devises of CAPD,
      peritonitis is still one of the major complications of CAPD. Fungus is a rare
      pathogen for peritonitis in CAPD, but it must be considered as a causative agent
      in cases of intractable peritonitis. This report describes the first case of
      Trichosporon beigelii (T. beigelii) peritonitis in CAPD in Japan. A nine year old
      boy with chronic renal failure due to bilateral vesicoureteral reflux was given
      CAPD treatment four years prior to admission. This patient had been admitted to
      our hospital frequently because of recurrent bacterial peritonitis. The
      peritonitis in CAPD was usually treated by changing the peritoneal fluid and
      antibiotic treatment. In this case T. beigelii was proved to be a pathogen of
      peritonitis by culture of CAPD fluid and also serum antibody titers. T. beigelii
      infection was successfully eradicated from the peritoneal cavity by
      administration of MCZ and by the removal of peritoneal catheter. The patient was
      switched from CAPD to HD. In the case of intractable peritonitis in CAPD, rare
      fungal pathogens such as T. beigelii must be considered as a causative agent.

PMID- 1402122
TI  - [Postplenectomy pneumococcal sepsis developed 2 year after pneumococcal
      vaccination].

PMID- 1402123
TI  - Techniques for intraoperative hyperthermia with ultrasound: the Dartmouth
      experience with 19 patients.
AB  - Over the course of 3 years, tumours of 19 patients were heated with ultrasound in
      the operating room during surgical resection. Immediately following
      intraoperative radiation therapy, thermocouples were inserted into tumour and
      adjacent normal structures. Patients were then given a 60-min heat treatment with
      ultrasound after a 10-15-min heatup period. Temperatures were measured at a total
      of 133 fixed locations for the 19 patient series. Temperature mapping was done in
      the tumour volume when logistically feasible. Treatment sites included colorectal
      (n = 3), portahepatus (n = 1), pancreas (n = 7), liver (n = 1), pelvis (n = 3),
      sacrum (n = 2), and abdomen (n = 2). A sterile, constant-volume water circulating
      system was utilized to control surface temperatures. Three generations of
      completely immersible transducers were designed over the course of this study
      with a 4-cm height specification. Since the ultrasound transducer was assembled
      on the sterile field during surgery, a 1, 2 or 3 MHz ceramic element was placed
      in either a 6, 8 or 10 cm diameter aluminium housing to conform the acoustic
      field to the tumour size. Average of the maximum temperatures attained was 46.6
      degrees C. Temperature with which 90% of all measured points equalled or exceeded
      (T90) was 39.2 degrees C. The T50 was 42.9 degrees C. This compared favourably
      with T90 and T50 of 38.8 and 41.9 degrees C, respectively, in our outpatient
      clinic series, in which superficial tumours were treated with a similar external
      applicator, and patient tolerance was often a treatment limitation.

PMID- 1402125
TI  - Intrinsic thermal response, thermotolerance development and stepdown heating in
      murine bone marrow progenitor cells.
AB  - Thermal response, thermotolerance development and stepdown heating (SDH) in the
      murine bone marrow granulocyte-macrophage (CFU-GM) progenitors were determined in
      vitro. Marrow was removed from femora and tibia, heated in McCoy's 5A medium plus
      15% FBS and cultured in soft agar in the presence of three different sources of
      colony stimulating factor. D0's (+/- SE) for survival curves of CFU-GM heated in
      vitro were 147 +/- 13, 71 +/- 9, 37 +/- 2, 19 +/- 0.7, 11 +/- 1, and 4.3 +/- 0.3
      min, for temperatures of 41.8, 42, 42.3, 42.5, 43 and 44 degrees C, respectively.
      Arrhenius analysis showed inactivation enthalpies of 812 +/- 9 KJoules/mole (193
      +/- 2 Kcal/mole) above, and 2142 +/- 157 KJoules/mole (509 +/- 37 Kcal/mole)
      below, an inflection at 42.5 degrees C. Thermotolerance development was evident
      during prolonged hyperthermia exposure at temperatures below 42.5 degrees C
      (chronic hyperthermia) as a change in the slope of the survival curves after
      approximately 110 min of heating. Thermotolerance development at 37 degrees C
      after exposure to temperatures of 43 degrees C or greater (acute hyperthermia)
      was assessed by fractionated heat treatments consisting of an initial heat
      treatment (15 min at 44 degrees C) followed by incubation at 37 degrees C and
      challenge with 15 min or 25 min at 44 degrees C. Maximum thermotolerance occurred
      after 210 and 330 min at 37 degrees C, respectively. The half-time for maximum
      thermotolerance development was 36 min. Depending on the amount of heat damage
      and the maximum amount of thermotolerance development, the decay of
      thermotolerance was complete after approximately 48-72 h at 37 degrees C. An
      exposure of 10 min at 44 degrees C before incubation at 40 or 41 degrees C
      (stepdown heating) reduced the slope of the 40 or 41 degrees C survival curves by
      inhibiting thermotolerance development that would have otherwise occurred. D0's
      were 100 +/- 19 and 45 +/- 5 min for 40 and 41 degrees C incubation preceded by
      10 min at 44 degrees C, respectively. These studies indicate that whole-body or
      regional hyperthermia protocols designed either to treat solid tumours or to
      purge leukemic stem cells from marrow ex vivo should avoid inadvertent
      temperature elevations to large volumes of marrow. Although, marrow progenitors
      are capable of thermotolerance development during exposure to temperatures up to
      42.3 degrees C, results suggest that conditions of stepdown heating may prevent
      thermotolerance development.

PMID- 1402124
TI  - Concurrent ferromagnetic hyperthermia and 125I brachytherapy in a rabbit
      choroidal melanoma model.
AB  - Ferromagnetic (FM) thermoseeds and radioactive (125I) seeds were combined in an
      episcleral plaque to give concurrent hyperthermia and irradiation for enhanced
      tumour destruction. A Greene melanoma cell line was utilized to study the
      interaction between these treatment modalities. We attached five FM thermoseeds
      (with an operating temperature of 48 degrees C) in parallel with alternating rows
      of 125I seeds onto the inner surface of each 14 mm Silastic plaque. Plaques were
      centred over a 3-6 mm (diameter) intraocular melanoma in each rabbit. Some
      rabbits were then placed within a heating coil, and their eye tumours were warmed
      rapidly to therapeutic temperatures (43.6 degrees C across the tumour base) while
      the temperature of normal conjunctiva across the globe did not exceed 38.5
      degrees C. Analysis of 49 treated eye melanomas showed 50% local tumour control
      at 41.7 Gy for 125I alone, whereas only 9.5 Gy were needed to give the same local
      control rate after 125I with concurrent FM hyperthermia. Thus, a thermal
      enhancement ratio of 4.4 was obtained. Hyperthermia alone gave a 20% tumour
      response rate, but responses were only temporary. We conclude that FM thermoseeds
      can be used to deliver biologically effective hyperthermia concurrently with
      radiation, thereby reducing the dose of radiation needed for tumour control.

PMID- 1402126
TI  - Variation in heat sensitivity through the cell cycle of M10 and Burkitt P3HR-1
      cells.
AB  - The cell-cycle age response to 44 or 45 degrees C hyperthermic treatment was
      studied in M10, a mutant of mouse L5178Y cells, and human Burkitt P3HR-1 cells
      synchronized by centrifugal elutriation. Survival response to 44 degrees C
      hyperthermia or radiation showed that Burkitt cells were relatively hyperthermic
      resistant and average in radiosensitivity, while M10 cells were relatively
      hyperthermic sensitive and substantially radiosensitive. A typical age-response
      to hyperthermia through the cell-cycle was observed in M10 cells, although no
      significant variation in the response to hyperthermia was demonstrated in Burkitt
      P3HR-1 cells. Combined effect of procaine with 44 degrees C 20-min treatment for
      Burkitt P3HR-1 cells showed a substantial enhancement of cytotoxicity in S phase
      cells. The probable implication of membrane composition, membrane changes due to
      heat and its modifying agents are discussed. Furthermore, when hyperthermia was
      combined with radiation in Burkitt P3HR-1 cells, cytotoxic enhancement was
      observed in G1/S boundary phase, not in S phase.

PMID- 1402127
TI  - Potentiation of hyperthermia in a murine tumour by metabolic inhibitors rhodamine
      123 and 2-deoxy-D-glucose or 5-thio-D-glucose.
AB  - Rhodamine 123 injected into mice on 3 days consecutively before a single
      hyperthermia treatment (45 degrees C for 15 min) potentiated hyperthermia as
      evidenced by an increased mean tumour growth delay of a transplantable murine
      mammary adenocarcinoma (MTG-B). Addition of three daily injections of either 2
      deoxy-D-glucose, or 5-thio-D-glucose, coordinated with the rhodamine 123, and
      administered before hyperthermia, resulted in an additional tumour growth delay,
      but not large enough to suggest an additional significant interaction between the
      two drugs and heat. This effect was obtained using doses of the glucose analogues
      which did not potentiate therapeutically when combined with heat without
      rhodamine 123. On the third day of treatments, rhodamine 123 or 5-thio-D-glucose,
      or the two drugs together, 60 min before heating, produced a longer growth delay
      compared with each combination treatment with drugs administered 15 min before
      heating. However, this effect was not significant. Results of these experiments
      suggest that in this murine tumour thermopotentiation can be attained by
      combining these two classes of metabolic inhibitors with hyperthermia.

PMID- 1402128
TI  - In vitro and in vivo responses of doxorubicin ion exchange microspheres to
      hyperthermia.
AB  - The utility of microspheres as targeted drug delivery agents is addressed with
      reference to using heat during formulation and to administration in combination
      with hyperthermia. It was demonstrated that rate of loading of the drug
      doxorubicin onto resin microspheres is enhanced under conditions of elevated
      temperature but this was shown to increase the incidence of microsphere
      aggregation. Total amount of drug loaded was related to time rather than
      temperature such that low temperature loading for up to 24 h produced optimum
      quality injectates. However, release of doxorubicin from microspheres was
      significantly increased during elevations of temperature to 43 degrees C. Thus,
      during hyperthermia doxorubicin release can be increased to provide periods of
      high drug availability targeted to tumour tissue for concomitant
      thermochemotherapy with microspheres. The therapeutic benefit derived from this
      combined therapy was assessed in 20 rabbits with VX2 carcinoma implanted in the
      liver. Hyperthermia was delivered by 2450 MHz microwave applicator to the
      exteriorized liver at 43 degrees C for 30 min, while chemotherapy was
      administered by intratumoural injection of doxorubicin microspheres (2.3 mg) into
      each tumour. Both hyperthermia and chemotherapy alone significantly reduced the
      size of tumours 10 days following treatment (p less than 0.01). However, in
      animals treated with both modalities, the size of tumours was significantly less
      than either treatment alone (p less than 0.05). These results provide a strong
      rationale for combining hyperthermia with targeted chemotherapy using
      microspheres.

PMID- 1402129
TI  - Effect of hyperthermia and protein kinase C inhibitors on DNA synthesis and cell
      proliferation on Ehrlich ascites tumour cells in vitro.
AB  - Effect of hyperthermia and/or protein kinase inhibitors on DNA synthesis and cell
      proliferation was investigated in Ehrlich ascites tumour cells in vitro. Both H-7
      and H-8, potent inhibitors of protein kinase C, suppressed DNA synthesis
      significantly, but HA1004, an inhibitor of cAMP- and cGMP-dependent protein
      kinase, did not. Hyperthermia increased greatly the suppressive activity of H-7
      and H-8 but not that of HA1004. H-7 also inhibited cell growth. These results
      suggest that the inhibition of protein kinase C enhances the suppression of DNA
      synthesis and the proliferation of tumour cells by hyperthermia.

PMID- 1402130
TI  - Differential thermal sensitivity of tumour and normal tissue microvascular
      response during hyperthermia.
AB  - The goal of this study was to investigate the heat sensitivity of the
      microcirculation in normal C3H murine leg muscle and a variety of transplanted
      tumour lines (KHT, SCC-VII, RIF-1, C3H mouse mammary carcinoma, two human mammary
      carcinomas MDA-468 and S5). Clearance rate of a radioactive tracer monitored
      following an intra-tissue injection was used as a measurement of microvascular
      integrity during heat treatment. Clearance rate in all tumours studied was
      significantly lower after 1 h of heating at 44 degrees C than the initial
      pretreatment clearance rate. Response of normal muscle differed from that of
      tumours in that the clearance rate after 1 h of heating at 44 degrees C was
      similar to the initial clearance rate. Vasculature in the KHT fibrosarcoma was
      more sensitive to heat treatment than that in other tumours. In response to a
      heat treatment at 43, 44, 45 and 46 degrees C the same level of microvascular
      damage occurred in half the time in KHT fibrosarcoma than in normal muscle.
      Furthermore, vascular damage in both muscle and KHT tumour followed the same
      relative isoeffect relationship, a 1 degree C change in temperature was
      equivalent to a change in heating time by a factor of two.

PMID- 1402131
TI  - Optimum excitation of phases and amplitudes in a phased array hyperthermia
      system.
AB  - In order to achieve a desired temperature distribution inside and outside of
      malignant tissues, optimization techniques could be used in phased array
      hyperthermia systems to control effectively the amplitude and phase of the
      radiating elements. The optimization of a four-element phased array hyperthermia
      system operating at 432 MHz is examined theoretically. The proposed technique is
      based on a detailed physical model of the tissue medium to be heated in terms of
      both electromagnetic and thermal properties. A penalty function technique using a
      Newton method is applied to determine the optimum phases and amplitudes of the
      array. Several array geometries have been studied and numerical results are
      presented.

PMID- 1402132
TI  - Three-dimensional theoretical SAR and temperature distributions created in brain
      tissue by 915 and 2450 MHz dipole antenna arrays with varying insertion depths.
AB  - Theoretical three-dimensional power deposition and temperature distributions were
      calculated for interstitial hyperthermia microwave antenna arrays driven at 915
      and 2450 MHz in brain tissue. Four dipole antennas were assumed to be placed in a
      2 x 2 cm array with varying insertion depths in cylindrical tumour models. The
      bioheat transfer equation was solved for the three-dimensional steady-state
      temperature distributions using a finite element method. Homogeneous and non
      homogeneous blood flow models were considered. As a basis of comparison of the
      various temperature distributions, the volume of the tumour heated to greater
      than or equal to 43 degrees C was calculated. SAR distributions calculated for
      the 915 MHz antenna arrays in brain tissue were very similar to those calculated
      for muscle. The 2450 MHz arrays showed similar behaviour to the 915 MHz arrays;
      however, as the insertion depth increased from slightly less than a full
      wavelength there was a single hotspot centred at the antenna junction. For the
      2450 MHz arrays, the predicted therapeutic tumour volumes were relatively
      constant over the entire range of insertion depths considered, and in fact, for
      most insertion depths considered, the model predicted the 2450 MHz arrays would
      heat larger therapeutic volumes than the 915 MHz arrays. For the 915 MHz array,
      at insertion depths between 7.8 and 14.6 cm there was a sharp decrease in the
      predicted therapeutic volume due to a proximal secondary hotspot in the normal
      tissue causing overheating. However, when the same size tumour at the same
      insertion depth was heated with the 2450 MHz array, the hotspot was in the
      tumour, adding to the volume of tumour that was heated to therapeutic
      temperatures.

PMID- 1402133
TI  - Automated mechanical thermometry probe mapping systems for hyperthermia.
AB  - In order to better assess temperature distribution patterns in patients, tissue
      equivalent phantoms, and experimental animals, mechanical devices and automated
      control systems for positioning temperature probes in implanted catheters and
      catheters laid on the skin surface have been developed. They employ stepper motor
      actuated roller and idler wheel drives to move the probes. Two devices
      incorporate positive positioners in addition to the drive rollers in order to
      obtain higher positioning accuracy where significant probe to catheter friction
      is present. Automated systems have been constructed which can simultaneously
      position, record and display data from up to 10 temperature sensors in a colour
      coded position versus temperature format to produce a real time two-dimensional
      colour-coded pseudo isotherm display. These thermal mapping devices have been
      used for characterizing the power deposition patterns of several large area
      microwave applicators (on the surface and at depth within tissue equivalent
      phantoms), for intraorgan temperature mapping in experimental animals, and for
      surface and subcutaneous temperature mapping during clinical treatments.

PMID- 1402134
TI  - BSD 2000 multi-applicator hyperthermia system using scattering- or S-parameters.

PMID- 1402135
TI  - Winner of the Lund Science Award 1992. Thermosensitization induced by step-down
      heating. A review on heat-induced sensitization to hyperthermia alone or
      hyperthermia combined with radiation.
AB  - A few minute's exposure to a high temperature (sensitizing treatment, ST) may
      substantially increase the cytotoxic and the radiosensitizing effect of a
      subsequent heating at a lower temperature (test treatment, TT). This phenomenon,
      which is known as step-down heating (SDH) or thermosensitization, has been
      observed both in cultured cells in vitro and in tumours and normal tissues in
      vivo. The effect of SDH increases with a lowering of TT temperature, but it is
      rapidly lost at temperatures very close to 37 degrees C. SDH-induced
      thermosensitization decays within a few hours, when an interval is inserted
      between ST and TT. In vitro results suggest an exponential decay of the SDH
      effect with half times ranging from 1.5- to 3.1 h. The effect of SDH increases
      with increasing ST time or temperature. For single heating, the Arrhenius plot is
      biphasic with activation energies of 500-800 and 1200-1700 kJ/mol above and below
      a break point temperature in the region 42.5-43.0 degrees C, respectively. For
      SDH, the Arrhenius plot gradually becomes monophasic with increasing severity of
      ST and it approaches asymptotically to an activation energy of about 400 kJ/mol.
      The reduction of the activation energy depends on cell survival after the priming
      ST and not on the specific ST heating time or temperature. SDH strongly enhances
      hyperthermic radiosensitization with a 5-6-fold reduction of the radiation dose
      required to achieve tumour control. The thermosensitizing and the
      radiosensitizing effects of SDH have several features in common. Both effects
      become more prominent when the TT temperature is decreased and when the ST
      heating time or temperature increases. In addition, the decay kinetics for both
      effects are comparable. For heat alone, the effect of SDH in tumour and normal
      tissue seems to be quantitatively similar. However, the therapeutic ratio may be
      increased by combining SDH with radiation. Biologically, the critical subcellular
      targets involved in the SDH effect have not been revealed. However, the ability
      of SDH to inhibit the clearance of heat-induced aggregation of proteins in the
      nucleus is interesting. Blockage of the nuclear function by proteins is a central
      theory in the present molecular biological models for both cell kill by heat and
      heat radiosensitization. Clinically, SDH may be an advantage since even a short
      exposure to high temperature increases the effect of an otherwise inadequate heat
      treatment. The disadvantages are that SDH complicates thermal dose calculations,
      and may cause unacceptable damage to normal tissue.

PMID- 1402136
TI  - Early experience of a commercial scanned focused ultrasound hyperthermia system.
AB  - Preliminary experiences of the Sonotherm 6500 scanned focused ultrasound (SFUS)
      system in the hyperthermic treatment of bulky tumours in breast, superficial
      sites and within the pelvis in 22 patients are reported. Tumour volumes ranged
      from 235 to 603 cm3 (breast), 105 to 209 cm3 (superficial sites) and 24 to 905
      cm3 (pelvis). Temperature distributions in 58 evaluable treatments were analysed
      in terms of temporal peak and time-averaged temperatures (highest and lowest
      temperatures, percentage of sensors exceeding index temperatures, etc.) achieved
      within scanned volumes. Mean number of sensors implanted into tumour was 14 in
      breast and superficial tumours and approximately 11 in pelvic tumours. Mean time
      averaged maximum and minimum temperatures for the best treatments (i.e. for each
      patient, that with the highest percentage of sensors recording time averaged
      temperatures greater than or equal to 42 degrees C) administered to patients with
      tumours in the breast and superficial sites were 44.6 +/- 1.7 degrees C and 39.7
      +/- 1.1 degrees C, respectively and the mean number of sensors exceeding 42
      degrees C was 58 +/- 19%. In the case of pelvic tumours these figures were 41.6
      +/- 0.9 degrees C, 40.0 +/- 0.6 degrees C and 8 +/- 12%, respectively. Patient
      tolerance to treatments was, in general, good. Areas where technical improvement
      of the system is appropriate and further research and development are required
      are identified; these should lead to a better realization of the potential of the
      SFUS technique, particularly for pelvic tumours.

PMID- 1402137
TI  - Quantitative determination of SAR profiles from photographs of the light-emitting
      diode matrix.
AB  - The utility of the light-emitting diode (LED) matrix, i.e. the qualitative
      localization of maxima and minima in the patterns of the specific absorption rate
      (SAR), can be extended to quantitative measurements by a method described. With
      the LED dipoles on the matrix representing light sources of similar
      characteristics, the minimal field strength necessary to produce light is a
      criterion which can be easily determined. From the power levels necessary to
      fulfil this criterion, relative SAR values have been calculated. The attenuation
      of field strength by the LED matrix has been measured by an additional dipole
      antenna with fibre-optic read-out, so that the calculated SAR profiles could be
      corrected for the relatively smaller attenuation near the edges. This technique
      has been tested for several set-ups in a 'Coaxial TEM applicator' and the
      resulting SAR profiles along the major axis of the aperture midplane were
      compared with SAR profiles determined using a single dipole E-field probe.
      Results show that, from a set of photographs at different power levels, SAR
      profiles can be constructed with limited accuracy along lines in any direction in
      the whole aperture midplane and by this the complete two-dimensional SAR pattern
      can be obtained.

PMID- 1402138
TI  - Risk of tumour growth along thermometry catheter trace: a case report.
AB  - A patient with recurrent rectal cancer was treated with the combination of
      radiotherapy plus hyperthermia. Intratumoral thermometry probes were introduced
      within closed-tip catheters, inserted through the buttocks under computed
      tomography (CT) control. Catheters were fixed to the skin to stay in place during
      the whole treatment series. At the end of the radiotherapy series, tumour
      progression was apparent. Seven months following treatment, tumour growth was
      visible at the insertion site of one of the catheters. This finding indicates
      that catheters should not be placed outside the treatment volume involved in any
      locally curative treatment.

PMID- 1402139
TI  - Risk of acute hypotension following epidural analgesia during deep regional
      hyperthermia: a case report.
AB  - A potentially dangerous complication occurring during deep regional hyperthermia
      is described. A patient receiving epidural analgesics for pain caused by a large
      pelvic recurrent rectal tumour was treated by hyperthermia induced by
      electromagnetic radiation. The epidural infusion pump failed during heating and
      further analgesics were administered by bolus injections into the epidural space.
      Following the second bolus injection, a severe drop in arterial blood pressure
      was observed. The most likely multifactorial pathogenesis is discussed and
      measures to avoid such an event are recommended.

PMID- 1402140
TI  - Experimental thermoradiotherapy of human tumour xenografts in nude mice; design
      of the hyperthermia system.
AB  - An experimental thermoradiotherapy study was started in 1986. For this study a
      hyperthermia system was developed for heating human tumours xenotransplanted into
      nude mice. The treatment device was a four-channel computer-controlled
      hyperthermia system. Temperature was monitored by microwave radiometry at 3 GHz.
      Specifications of the radiometer were evaluated first under reference conditions.
      Subsequently, thermal dosimetry was studied using non-invasive measurement of
      brightness temperature, TOR. Hyperthermia treatments were simulated in phantom
      material with radiometric monitor values, TR, of 40 and 41. In conjunction with
      the parameters of TOR, surface temperature, T0, and water bolus temperature, TW,
      thermal modelling was performed. Influence of a perfused phantom also was studied
      on microwave thermometry.

PMID- 1402141
TI  - Comparative study of thermoradiosensitization by misonidazole and metronidazole
      in vivo: antitumour effect and pharmacokinetics.
AB  - Tumour control by local hyperthermia (43.5 degrees C, 30 min) and radiation (20
      Gy) given in combination with misonidazole (MISO) or metronidazole (METRO) was
      studied using FSa-II murine fibrosarcoma. When MISO or METRO (5 mmol/kg) was
      given 30 min before heat and subsequently treated with radiation, tumour
      regression was observed for both agents. Radiation dose-response curves for MISO
      and METRO with heating at 43.5 degrees C for 30 min were identical. Mouse foot
      reaction was used to evaluate local toxicity following combined heat, a
      nitroimidazole and radiation treatment. MISO enhanced the magnitude of foot
      reaction and prolonged the recovery time compared with heat plus radiation
      controls. There were no observable differences of foot reaction between animals
      treated with heat plus radiation and those animals treated with heat, radiation
      and METRO. Pharmacokinetics of the nitroimidazoles heated at 43.5 degrees C for
      30 min in FSa-II tumours were investigated as a possible mechanism of thermal
      sensitization. Local hyperthermia did not alter the pharmacokinetics of METRO.
      Tumour concentration and tumour/plasma ratio of MISO were slightly decreased
      during heating. Since the hypoxic metabolism of the nitroimidazoles did not
      increase significantly during the heat treatment, the thermal enhancement of MISO
      or METRO radiosensitization cannot be explained by the increase in hypoxic
      cytotoxicity of the nitroimidazoles at elevated temperature alone. The two
      nitroimidazoles also were not accumulated in the tumour after heating. Therefore,
      alternation of pharmacokinetics is not the major mechanism for the thermal
      enhancement of nitroimidazole radiosensitization. The METRO radiosensitization
      effect became identical to that of MISO at elevated temperatures is of particular
      importance in clinical radiosensitization. The very low local and systemic
      toxicity together with the high efficacy of METRO at elevated temperatures will
      make it an attractive candidate as a future clinical radiosensitizer.

PMID- 1402142
TI  - Tolerance of intraperitoneal chemohyperthermia with mitomycin C: in vivo study in
      dogs.
AB  - Tolerance of intraperitoneal chemohyperthermia (IPCH) with mitomycin C (2 mg/kg)
      by irrigation of the peritoneal cavity via a closed circuit system was evaluated
      in Beagle dogs for possible use in the management of human peritoneal
      carcinomatosis. Of dogs, 24 underwent three digestive anastomoses each. They were
      randomized into three groups: control (n = 6), intraperitoneal hyperthermia (n =
      8) and IPCH (n = 10). Peritoneal temperatures were maintained between 41-43
      degrees C for 60 min. Tolerance was evaluated through clinical follow-up,
      biological samples (serum electrolytes, blood counts and serum enzymes),
      histological examinations and post-mortem macro- and microscopic controls of
      anastomosis. Mortality and morbidity rates were not different in the three
      groups. No anastomotic leakage occurred. Evidence of biological toxicity was
      minimal. Histological examinations showed no definitive tissue damage. IPCH
      appears to be a safe and reliable device in dogs. Plans to combine IPCH with MMC
      in surgical resection of patients with peritoneal carcinomatosis are underway.

PMID- 1402143
TI  - Effects of a second heating on rat liver blood flow.
AB  - Effects of a second heating on blood flow in the liver and cardiac output were
      studied in Fischer rats. Heating was done by an experimental capacitive heating
      device using 8 MHz radiofrequency. Thermometry was performed at seven points
      around the liver with thermocouples. Blood flow and cardiac output were measured
      with the radioactive microsphere method. The liver was preheated for 30 min at 41
      or 43 degrees C, and then reheated 1-7 days later at 41 degrees C for 15 min.
      Hepatic arterial blood flow, portal venous blood flow and the cardiac output were
      measured immediately before and at the end of the reheating. Heating the liver at
      41 degrees C for 15 min without preheating slightly increased the hepatic
      arterial blood flow, and reheating 1-7 days after the first heating caused a
      greater increase in the hepatic arterial blood flow. Increase in hepatic arterial
      blood flow caused by reheatings pointed to the development of thermotolerance or
      thermal adaptation in the hepatic artery. When the liver was heated at 41 degrees
      C for 15 min without preheating, the portal venous blood flow remained almost
      unchanged 1-7 days after the heating. On the other hand, a reheating at 41
      degrees C for 15 min applied 1-7 days after the preheating reduced the portal
      venous blood flow. Reduction in portal venous blood flow was approximately
      parallel to reduction in cardiac output by reheating, pointing to the existence
      of a causal relationship. Reduction in portal venous blood flow by reheating may
      also be, in part, due to the decrease in the splanchnic blood flow resulting from
      a systemic adaptation to the heat stress.

PMID- 1402145
TI  - Effects on the expression of heat shock proteins by step-down heating and
      hypothermia in rat hepatoma cells with a different degree of heat sensitivity.
AB  - Thermosensitization induced by pretreatment at supra- and subnormal temperatures,
      rate of protein synthesis and expression of the major heat shock proteins under
      such conditions was investigated in relation to intrinsic heat sensitivity of rat
      hepatoma cells, i.e. Reuber H35 and HTC. The high degree of heat susceptibility
      of H35 cells was reflected by a high degree of thermosensitization after
      pretreatment by heat (step-down heating) at temperatures of 42-44 degrees C for
      30 min or cold for 16 h at temperatures ranging from 0 to 25 degrees C.
      Sensitization under step-down heating conditions was found to be paralleled by a
      delayed recovery of protein synthesis. Despite an increased relative rate,
      enhancement of the absolute rate of synthesis of the major heat shock proteins,
      HSP28, HSP60, HSP68, HSP70, HSP84 and HSP100, was less pronounced during step
      down exposure. Comparable results were obtained during recovery of sensitized H35
      cells at 37 degrees C after exposure to heat following pretreatment at 0 degrees
      C. Furthermore, clear differences in the regulation of the specific HSP
      synthesis, depending on the particular treatment protocol, were observed.

PMID- 1402144
TI  - Lethal interaction between heat and methylene blue in Escherichia coli.
AB  - Hyperthermia treatment is shown to act synergistically with methylene blue (MB),
      from the end point of lethality in Gram-negative Escherichia coli bacteria. That
      this lethality is correlated to the damage produced in DNA by the dye is deduced
      from the fact that bacteria differing in capacity for repair are almost equally
      sensitive to heat, but differ considerably in sensitivity to concomitant heat and
      dye treatment. It is demonstrated that the damage is repairable by the excision
      repair system. The role of temperature seems to be that of facilitating the
      incorporation of the dye, which enables the latter to intercalate into the DNA.
      Ability of the outer membrane of E. coli AB1157 bacteria to act as a barrier to
      the penetration of MB remains almost intact up to 46 degrees C, but above this
      temperature it seems to disrupt abruptly (but reversibly), leading to
      inactivation of the cells by the dye. Since hyperthermia is in current use for
      the treatment of cancer, it is suggested that if this synergism also exists in
      mammalian cells, MB could eventually be used independently of its photodynamic
      action as an adjuvant in cancer therapy.

PMID- 1402146
TI  - On speaking a foreign language.

PMID- 1402147
TI  - The false localizing signs of increased intracranial pressure.
AB  - False localizing signs, although rare, indicate significant increased
      intracranial pressure with tissue shift, has occurred. A review of the historical
      perspective highlights the discovery of these false localizing signs, and
      exploration of the anatomic and physiologic causes provides important insight for
      neuroscience nurses. Critical thinking skills, and a world view paradigm for
      clinical practice are developed upon an in-depth understanding of neurologic
      dysfunction. Collaborative relationships are enhanced by an interdisciplinary
      approach to assessment of the critically ill neuroscience patient.

PMID- 1402148
TI  - An unusual nursing challenge: Guillain-Barre syndrome following cranial surgery.
AB  - An 84 year-old white female developed Guillain Barre syndrome (GBS) following a
      craniotomy for resection of a meningioma. GBS is a rare, idiopathic disease which
      presents multiple nursing challenges. To effectively care for the patient with
      GBS, it is necessary to be familiar with symptomatology, incidence and pathology.
      Using this information, nursing assessment may be performed and interventions
      developed and individualized as needed.

PMID- 1402149
TI  - Nasoduodenal feeding tubes: prevention of occlusion.
AB  - Blockage of nasoduodenal feeding tubes is costly in terms of materials and
      nursing time, and traumatic to the neuroscience patient. A laboratory
      experimental study explored ways to decrease obstruction of small bore
      nasoduodenal feeding tubes when medications are given concurrently with
      continuous tube feeding. The first part of the study examined type and form of 4
      medications in relation to frequency and timing of tube blockage. Trimethoprim
      sulfamethoxazole (Septra) in dissolved pill form blocked tubes most frequently
      (F10,77 = 10.333, p < .001) and in the shortest time (F10,77 = 10.534, p < .001).
      The second part of the study examined different irrigation methods. Irrigation
      before and after administration of medication and irrigation after medication
      administration only were significantly better than no irrigation in preventing
      blockage, both in terms of number of occlusions (F2,87 = 5.486, p < .01) and time
      to occlusion (F2,87 = 4.556, p < .02). The fact the study was performed in vitro
      rather than in vivo was a limiting factor. However, results of the study suggest
      trimethoprim sulfamethoxazole forms occlusions, especially in dissolved form.
      Elixir of this medication should probably be used whenever available. This study
      also found that irrigating the tube before and after administration of
      medications was the most effective of the 3 options examined.

PMID- 1402150
TI  - Cryptococcal meningitis in patients with AIDS.
AB  - In the U.S., cryptococcal meningitis is the most common form of fungal meningitis
      and a major cause of morbidity and mortality among immuno-suppressed patients. In
      the AIDS patient, cryptococcal meningitis often presents with fever and headache
      and is best treated with intravenous amphotericin B and oral flucytosine, or
      fluconazole. However, toxic effects may result from the therapy. This disease
      frequently relapses necessitating life-long treatment to prevent reactivation.
      Essential management principles focusing upon health education are presented to
      promote comprehensive nursing care for patients testing positive for the human
      immunodeficiency virus who also have cryptococcal meningitis.

PMID- 1402151
TI  - The transoral approach to the cervical spine.
AB  - The transoral surgical approach is useful for operating on structures at the base
      of the brain and the upper cervical spinal cord. For example, this route has been
      used for resecting spinal tumors and clipping vertebrobasilar aneurysms. In the
      past, this surgical approach was not advocated due to concerns about exposure and
      infection. However, the availability of the microscope, computed tomography,
      computed myelotomography, magnetic resonance imaging and intraoperative
      radiography as well as more effective techniques have improved the diagnosis of
      pathology of the craniovertebral junction and surgical performance. An
      understanding of the operative procedures involved with this approach assists the
      neuro-science nurse in preoperative teaching and anticipating potential
      postoperative complications.

PMID- 1402152
TI  - Olfaction: the neglected sense.
AB  - Although olfactory complaints prompt an estimated 200,000 people each year to
      seek medical consultation in the U.S., there is a dearth of information available
      in the nursing literature. Recent research links olfaction to degenerative
      processes in Alzheimer's disease, Parkinson's disease and human immunodeficiency
      virus infection. This article reviews anatomy and physiology of the olfactory
      system, describes alterations in smell function and reviews assessment with the
      University of Pennsylvania Smell Identification Test and odor detection threshold
      testing. Nurses can advocate thorough assessment and prompt treatment of
      associated conditions, and educate the patient and family regarding ways to
      maximize current functioning when olfaction is impaired.

PMID- 1402153
TI  - Implementing managed care and case management: the neuroscience experience.
AB  - The case management model for patient care in the neuroscience area was recently
      implemented in the neurosciences area at a tertiary care hospital. Understanding
      of the concepts of case management and managed care were essential to the
      implementation process. Clustering of case types and appointment of group leaders
      made the development of individual care maps a manageable task. Case management
      of 2 case types, Parkinson's disease and Guillain Barre syndrome are described,
      including the rationale for selection, care map development and education. The
      process of continuing education focused on operational issues regarding
      utilization of the map and professional issues such as health teaching
      responsibilities.

PMID- 1402154
TI  - Living with spina bifida.
AB  - Health care workers are normally the ones who surround family members as they
      first begin to cope with spina bifida. It is important to assess family stressors
      and work with family members to formulate a care plan which assists them to cope
      with this child. Helping these children grow in society, within our schools and
      in their jobs, shows that continual observations and interventions may be
      necessary to maintain optimal growth. I have had the opportunity here to share
      personal experiences. I can truly say that I look forward to the opportunities
      ahead and realize that success lies not in my job, but within me.

PMID- 1402155
TI  - The neuroscience nurse as an expert witness.
AB  - Serving as an expert witness in cases alleging nursing negligence is an
      interesting, rewarding and stressful role. Having knowledge about qualifications
      of an expert, what is expected of the expert, how to assess adequacy of nursing
      care, and how to bill for services may lower the stress. If after careful
      consideration you choose to serve as an expert witness, you should experience
      satisfaction knowing you are fulfilling a professional responsibility to maintain
      standards of care and to protect nurses accused unjustly of negligence.

PMID- 1402156
TI  - Ticlopidine hydrochloride.
AB  - Ticlopidine, a new prototype antiplatelet agent, offers a significant alternative
      in the primary and secondary prevention of atherothrombotic stroke. While 2
      multicenter trials demonstrated benefits of ticlopidine, this drug is not without
      risks and limitations and more studies are indicated. The neuroscience nurse must
      apply current knowledge about ticlopidine in the care for patients receiving
      ticlopidine therapy.

PMID- 1402157
TI  - [Surgical correction of atrioventricular discordance--results and follow-up].
AB  - Between January 1977 and October 1991, 47 consecutive patients with
      atrioventricular discordance, ventriculoarterial discordance, and two ventricles
      underwent intracardiac repair at the Heart Institute of Japan. Their ages at
      operation ranged from 2 months to 21 years (average 9.2 years) and period of
      follow-up ranged from 1 month to 168 months (average 65.1 months). There were
      five basic anatomic types according to the associated anomalies, grouped into (1)
      situs solitus, ventriculoarterial (V-A) discordance or double-outlet right
      ventricle (DORV), ventricular septal defect (VSD) and pulmonary outflow tract
      obstruction (POTO) (31 patients); (2) situs solitus, V-A discordance and VSD (6
      patients); (3) situs solitus, V-A discordance and tricuspid regurgitation (TR) (2
      patients); (4) situs inversus, V-A discordance or DORV, VSA and POTO (7
      patients); (5) situs inversus, V-A discordance and VSD (1 patient). TR was
      evident preoperatively in 13 patients (28% of 47 patients), one of whom had
      Ebstein's anomaly. The conventional operation, which consisted of closure of VSD
      (34 patients), posterolateral pulmonary outflow enlargement (2 patients),
      tricuspid valvuloplasty (2 patients), and tricuspid replacement (1 patient) using
      the anatomical right ventricle as the systemic ventricle, was performed in 35
      patients (RV group). The anatomic correction (so-called "double switch
      operation"), the new alternative operation using the anatomical left ventricle as
      the systemic ventricle, was achieved in 12 patients (LV group). Anatomic
      correction consisted of Senning and RV-PA ECR in 3, Mustard and RV-PA ECR in 4,
      Senning and arterial switch in 2, and Mustard and arterial switch in 1
      patient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402158
TI  - [Analysis of lymph node metastatic pattern in relation to prognosis and
      recurrence in pN2 resected lung cancer patients].
AB  - Lymph node metastasis was analyzed quantitatively with 4 categories and relation
      to post surgical survival and recurrence pattern was studied in patients with pN2
      primary lung cancer who underwent relatively curative or relatively noncurative
      resection of the tumors. There was no relation between metastatic coefficient and
      post surgical survival, however, better survival was observed when the metastatic
      ratio and metastatic frequency were low and metastatic mode was random or skip
      pattern rather than sequential pattern. Metastatic coefficient and metastatic
      frequency were higher in cases with recurrence in lymph nodes but the former was
      lower and the latter was higher in cases with recurrence in intra-pulmonary
      dissemination or metastasis. There was no relation between metastatic coefficient
      and distant metastasis but metastatic frequency was lower in cases with
      recurrence in distant metastasis. Cases with sequential lymph node metastasis
      showed a tendency of lymph node recurrence and intrapulmonary metastasis and
      those with random or skip metastasis of lymph nodes had a tendency of distant
      metastasis.

PMID- 1402159
TI  - [Total repair for truncus arteriosus].
AB  - Total repair for truncus arteriosus using an external conduit was performed in 12
      patients from 1978 through 1989. Six cases were infants (mean age: 3.4 months)
      and 6 were children (mean age; 1 years 9 months). Two cases had Collet-Edwards
      type II truncus and the other 10 cases had type I truncus. One of the infants was
      associated with an interruption of the aorta and another had a severe
      regurgitation of the truncal valve (TrV). For external conduits, we used a non
      valved conduit in one infant, a composite valved conduit of Dacron containing a
      heterograft valve in 4 children and a valved pericardial roll made of an
      autologous or porcine pericardium in 5 infants and 2 children. One infant with a
      severe regurgitation of the TrV needed valve replacement along with enlargement
      of the annulus of the TrV. One infant who had replacement of the TrV died early
      postoperatively. Another infant died 10 months after total repair due to an
      infection of an external conduit. Cardiac catheterization was performed in all 10
      survivors. The mean value for the systolic pulmonary/systemic pressure ratio
      decreased from 0.98 +/- 0.09 preoperatively to 0.36 +/- 0.09 postoperatively.
      Replacement of an external conduit was performed due to a conduit stenosis in 2
      children and 1 infant, 10 years and 2 months, 7 years and 9 months, and 1 year
      and 8 months after the total repair, respectively. In one of these 2 children,
      replacement of the aortic valve was performed due to a severe aortic
      regurgitation. We conclude that our results of total repair for truncus
      arteriosus were satisfactory. However, it remains to be solved how to manage an
      infant with truncus arteriosus associated with a severe regurgitation of the TrV.

PMID- 1402160
TI  - [The calcified ascending aorta--preoperative evaluation and intraoperative
      management].
AB  - Aortic calcification was evaluated preoperatively by computed tomography (CT) in
      136 of 275 candidates for coronary artery bypass surgery (age range, 30-80) years
      (mean 60.2 years), including 110 men and 26 women), from April 1989 to March
      1991. Calcification in the mid-ascending aortic wall was detected in 20 (14.7%)
      cases, calcification in all regions of the aorta was more common in patients
      older than 60 years (22.5%, n = 71), than younger (6.2%, n = 65) (p less than
      0.01). Atherosclerosis of the ascending aorta was identified intraoperatively in
      25 (18.3%) cases. Practically, the specificity of CT findings was excellent
      (98.3%), but the sensitivity was less satisfactory (72.0%) due to the presence of
      atherosclerosis without calcification. In cases of arteriosclerosis of the
      ascending aorta, great care was taken to prevent embolism secondary to a
      dislodged atheromatous plaque. The "aortic no-touch technique", with in situ
      internal thoracic artery and right gastroepiploic artery anastomosis under
      ventricular fibrillation, was performed in 6 cases, a single aortic cross-clamp
      was applied in 19 cases, and conventional methods were employed when the
      ascending aorta was normal or the "no-touch" or "single-clamp" procedure could
      not be used (control, 111 cases). No neurologic complications occurred in the "no
      touch" group, while 2 cerebral infarctions occurred in the single-clamp group
      (10.5%) and the control group (1.8%) respectively. These differences between
      groups was not significant. Patients with a calcified ascending aorta are at
      higher risk for neurologic complications of coronary bypass. The risk can be
      decreased by minimizing surgical trauma to the ascending aorta by the use of "no
      touch" techniques.

PMID- 1402161
TI  - [The local hyperthermochemotherapy for pleural carcinomatosis].
AB  - Local hyperthermochemotherapy was performed in 17 cases to control malignant
      effusion and intrathoracic disseminated lesions. Of these 15 patients, 11 cases
      primary lung cancer, 4 cases metastatic lung cancer had pleural carcinomatosis
      and 2 cases were malignant diffuse mesotheliomas. The procedure was
      radiofrequency hyperthermia (13.56 MHz) maintaining the peripleural temperature
      at 42-43 degrees C for 45-60 minutes, combined simultaneously with the
      intrathoracic administration of cisplatin (1-2 mg/m2, bolus) through a thoracic
      double lumen trocar tube. The treatment was repeated from 2 to 4 times at 7-day
      intervals. In 14 cases (87.5%) complete or partial response according to the
      criteria of the Japan Lung Cancer Society were obtained. There were 2 cases of no
      change and one case that was impossible to evaluate. In one lung cancer case, the
      disappearance of pleural disseminated lesions was confirmed by flexible
      thoracoscopy after the procedure. In 12 cases, there were abdominal complaints
      due to side effects of the hyperthermochemotherapy, such as vomiting and nausea,
      but these symptoms were milder than those caused by intravenous injection of anti
      cancer agents, for example cisplatin, in conventional chemotherapy treatment. The
      median survival time and 2 years survival of the patients with the present
      procedure were 15 months and 41.7% respectively. Although distant metastases
      appeared in most cases, none had local recurrence and particularly noteworthy
      pleural effusion was well controlled. The above experience suggested that the
      local hyperthermochemotherapy is useful to control pleural effusion and can
      improve the quality of life of patients with pleural carcinomatosis.

PMID- 1402162
TI  - [Reinfusion of autologous platelet-rich plasma improves hemostasis after
      cardiopulmonary bypass].
AB  - Although it is reported that postoperative bleeding is reduced by reinfusing
      autologous platelet-rich plasma (PRP) after cardiopulmonary bypass (CPB), the
      effect of PRP on hemostasis is not reported in detail. We prepared PRP and fresh
      whole blood (WB) from the blood of seven patients each prior to their undergoing
      CPB, and reinfused them autologously to the patients intravenously after the CPB
      was terminated. In this article, the effect on hemostasis of autologous PRP and
      WB was described. Platelet aggregation rates and blood coagulation factors were
      examined before, during and after bypass. Platelet counts, ADP-induced platelet
      aggregation and the activities of coagulation factors II, V and VII-X were
      significantly greater in prepared PRP than in WB (p less than 0.01 or p less than
      0.05). A mean volume of 724 +/- 109 ml of PRP or 401 +/- 63 ml of WB was
      reinfused within about 30 minutes after heparin was neutralized by protamine
      sulfate. The platelet counts increased from 4.3 +/- 1.4 x 10(4)/mm3 to 14.1 +/-
      1.6 x 10(4)/mm3 after PRP reinfusion and the platelet aggregation rates increased
      significantly (p less than 0.01) after PRP reinfusion compared to WB transfusion.
      The activities of coagulation factors VII-X also increased significantly (p less
      than 0.05) after reinfusion of PRP when compared to transfusion of WB. The
      activated partial thromboplastin time decreased to 1.2 times the baseline in the
      PRP group but remained 1.5 times the baseline in the WB group (p less than
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402163
TI  - [Assessment of long-term systemic ventricular function after the surgical repair
      in patients with atrioventricular discordance].
AB  - Long-term systemic ventricular function at rest and during supine bicycle
      exercise was studied in 12 patients with atrioventricular discordance (AVD group)
      using multigated radionuclide blood pool imaging. For comparison, similar
      measurements were made in eight children (control group). The mean age at the
      exercise test was 12.3 years in AVD group and was 14.8 years in the control
      group. In AVD group, ages at the operation ranged from three to 21 years (mean
      12.3 years), and the exercise test was performed from one to 9.8 years after the
      operation (mean 5.3 years). The operative procedures in AVD group consisted of
      closure of the ventricular septal defect in 11 patients, extracardiac conduit
      between the left ventricle and the pulmonary artery in nine patients, postero
      lateral left ventricular outflow reconstruction in two patients, tricuspid
      annuloplasty in one patient, and tricuspid valve replacement in one patient.
      Exercise tolerance of AVD group was less than that of the control group. Heart
      rate and blood pressure were significantly increased during exercise in both
      groups. In the control group, end-diastolic count index (EDCI) (= end-diastolic
      volume) remained unchanged and end-systolic count index (ESCI) (= end-systolic
      volume) decreased during exercise. In contrast, both EDCI and ESCI were decreased
      in AVD group. As a consequence, systemic right ventricular ejection fraction
      (RVEF) increased during exercise in the control group, but remained unchanged in
      AVD group. Although stroke count index (SCI) (= stroke volume index) did not
      increased during exercise in AVD group, output count index (OCI) (= cardiac
      index) increased with the increase of heart rate.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402164
TI  - [A study of arrhythmia following pulmonary operation in patients with
      bronchogenic carcinoma].
AB  - A total of 238 patients undergoing resection of lung cancer were studied for the
      occurrence of postoperative arrhythmia. Transient arrhythmia was observed in 43
      of them (18.1%). Ninety-one percent of 43 patients developed atrial fibrillation
      (Af), even though no arrhythmia was noted on ECG in any patient preoperatively.
      Cardiac dysrhythmia occurred 5.2 +/- 3.8 days after operation and lasted for 1.3
      +/- 0.9 days (mean +/- SD). There was a significant difference (p less than 0.05)
      in the incidence of postoperative arrhythmia between the male group (39/188 =
      21%) and the female group (4/50 = 8%), however the cause of a difference is
      unknown. The incidence was higher in patients undergoing pneumonectomy than in
      those undergoing lobectomy. Patients, who suffered from postoperative arrhythmia,
      has significantly low values on pulmonary function test (FEV1.0% = 68.7%)
      preoperatively. The increased cardiac load after the reduction of the pulmonary
      vascular bed was regarded as the most important factor of arrhythmia.
      Prophylactic administration of digoxin was performed in another 61 male patients
      after resection of lung cancer. And it was found to be effective in decreasing
      the incidence of postoperative atrial fibrillation (5/61 = 8%).

PMID- 1402165
TI  - [Efficacy of nicorandil on myocardial protection during coronary artery bypass
      grafting--a comparison with diltiazem].
AB  - Diltiazem (DTZ), a calcium slow channel blocker, is estimated to be highly
      effective for myocardial protection and the prevention of perioperative coronary
      spasms (PCS). However, the use of high doses of DTZ sometimes results in
      difficulty in coming off cardiopulmonary bypass due to negative chronotropic
      activity. Nicorandil (NCD) has remarkable coronary vasodilating effect but
      possesses little negative chronotropic activity. The purpose of this study was to
      compare NCD with DTZ with respect to effect on myocardial protection during
      coronary artery bypass grafting (CABG). As parameters, excess lactate (delta XL),
      redox potential (delta Eh), left and right ventricular stroke work indices
      (LVSWI, RVSWI), cardiac index (C.I.), systemic vascular resistance index (SVRI.),
      myocardial isoenzymes (CK-MB, LDH1), number of PCS and recovery time of
      chronotropic action were used. delta XL, delta Eh, LVSWI, RVSWI, C.I., SVRI, CK
      MB, LDH1 were measured at 0, 1, 3, 6, 9, 18 and 24 hours after the removal of
      aortic cross clamping. The degree of chronotropic action was evaluated by the
      length of the recovery time to self beat or normal sinus rhythm after the removal
      of aortic cross clamping. Forty patients who underwent CABG with retrograde cold
      blood cardioplegia between Dec. 1989 and May 1991 were divided into the NCD group
      (n = 20), in which 1.1 micrograms/kg/min NCD was continuously administered from
      the beginning of the operation and the DTZ group (n = 20), in which the initial
      St. Thomas cardioplegia containing 5 mg/L and subsequent cold blood cardioplegia
      solution contained DTZ 3.5 mg/L, for a total DTZ dose of less than 10
      mg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402166
TI  - [A case report of radiation osteomyelitis 9 years after irradiation for thymoma].
AB  - Radiation osteomyelitis of the sternum is rare and usually difficult to cure. A
      75-year-old man, who had undergone an exploratory sternotomy for a mediastinal
      tumor, not resected after all, 9 years earlier and received radiation therapy
      successively for the histological diagnosis of malignant thymoma, was admitted to
      our hospital with the chief complaint of fever and pus discharge of the anterior
      chest wall. He also suffered from diabetes mellitus. The skin around the fistula
      was dark-red and atrophic due to irradiation dermatitis and the manubrium was
      fissured in the midline. Open drainage and two-stage operation of direct closure
      was tried in vain. This case was treated successfully by resection of necrosed
      portion of sternum and pectoral muscle flap closure.

PMID- 1402168
TI  - [Double valve replacement for secondary atrioventricular regurgitation due to
      dilated cardiomyopathy--a case report].
AB  - A successful surgical case of double valve replacement for a patient with dilated
      cardiomyopathy was performed. A 45-year-old man was admitted to our hospital with
      paroxysmal atrial fibrillation and congestive heart failure. Echo cardiogram and
      cineangiography showed dilatation and decreased contraction of the left
      ventricle. A diagnosis of dilated cardiomyopathy was established since neither
      coronary artery disease nor valvular disease were observed. He was treated with
      medication of diuretics and pacemaker implantation. However, mitral and tricuspid
      regurgitation occurred and progressed 7 years later. Since then, he repeated
      admission and discharge against the strong medication. He became medically
      uncontrollable at the age of 58. Because of this, surgical treatment had to be
      considered. Double valve replacement for mitral and tricuspid valve was performed
      on September, 1989. Avoidance of cardiopulmonary bypass was only possible with
      the aid of catecholamine. Poor left ventricular function and pleural effusion
      frequently shown on chest X-ray film complicated the postoperative course. And
      with hospital treatment, he discharged three months after the operation. He has
      been doing well without any significant complaint during the past two years and
      cardiomegaly has been decreasing as well.

PMID- 1402167
TI  - [Ischemic cardiomyopathy associated with ischemic mitral regurgitation--a case
      report of successful repair].
AB  - We experienced a case of 62-year-old man with ischemic cardiomyopathy and mitral
      regurgitation. He had a heart failure of New York Heart Association class IV
      together with unstable angina. His further examination showed an enlarged left
      ventricle with markedly reduced ejection fraction (12.9%) and ischemic mitral
      regurgitation of grade III associated with 3-vessel disease. He underwent three
      coronary artery bypass graftings and mitral annuloplasty by a modification of
      Kay's method. He showed a remarkable improvement of heart failure and cardiac
      function together with a disappearance of mitral regurgitation. He discharged
      from hospital in NYHA class II on the 50th postoperative day and lives an almost
      normal life now. Operative indication and management of ischemic cardiomyopathy
      and mitral regurgitation were discussed.

PMID- 1402169
TI  - [A successfully treated case of thoracic meningocele with von Recklinghausen's
      disease].
AB  - Intrathoracic meningocele is an uncommon disease. Only 95 cases in the foreign
      literature and 13 cases in Japanese literature have been reported since Phol
      Meningocele occurs most frequently in the sacral and lumbar spinal regions. In
      this present paper, an 18-year-old female with intrathoracic meningocele
      associated with neurofibromatosis is described. The patient was admitted to our
      Surgical Clinic with a complaint of constrictive pain in the upper chest. The
      meningocele was diagnosed preoperatively and resected surgically by left
      thoracotomy. The patient has been followed up to for six years without any
      evidences of local recurrence. However, she recently complains of headache and
      weakened eyesight because of pituitary tumor, the operative indication of which
      is now discussed.

PMID- 1402170
TI  - [A successfully treated case of empyema with a large tracheal fistula after a
      radical operation of esophageal cancer by fixation and plombage with major
      pectoral muscle flap].
AB  - We reported a successfully treated case of empyema with a large tracheal fistula
      which had developed after a radical operation of esophageal cancer (reconstructed
      with stomach). This 59-year-old male was treated by the method of fixation and
      plombage with major pectoral muscle flap and thoracoplasty, because we could not
      use the omentum that were frequently used nowadays for closure of the fistula.
      The size of the tracheal fistula was a large as the main bronchus
      bronchoscopically. Postoperative care were the following, the endotracheal tube
      was inserted from the tracheal stoma to the left main bronchus and 9 days left
      hemi-ventilation was performed. Continuous suction was performed at the same time
      from the right main bronchus in order to prevent secretion and blood pour into
      the left lung. Bronchoscopical examination done 28 postoperative day, the small
      fistula remained the tip of the muscle flap. But 72 postoperative day, the
      surface of the fixed muscle flap was replaced by normal bronchial mucomembrane
      and tracheal fistula was obliterated. Major pectoral muscle could be used as
      local flap to obliterate empyema cavity associated with tracheal fistula. We
      believe that utilizing an muscle flap for those who had undergone abdominal
      operation like our case is a valuable method.

PMID- 1402171
TI  - [Atrial septal defect associated with von Willebrand's disease--a case report].
AB  - Von Willebrand's disease is common hemorrhagic disorder that deserves particular
      attention in the patient undergoing open-heart surgery, because of perioperative
      unexpected bleeding. The present case is atrial septal defect associated with
      Willebrand's disease, affecting a 19-year-old female who has the past history of
      bleeding tendency with frequent subcutaneous bleeding. It is mandatory to
      maintain adequate levels of both factor VIII coagulation and ristocetin cofactor
      activities during the perioperative period. An infusion study of heat-treated
      evaluate the response and half-life of both factor VIII coagulation and
      ristocetin cofactor activities; and to calculate the effective dose and duration
      of the drug action as well as to formulate a protocol for patient's management in
      the perioperative periods in order for the surgical intervention to be performed
      uneventfully. Our case demonstrated that it is possible to perform an open heart
      surgery in patients with von Willebrand's disease without major bleeding as far
      as the levels of both factor VIII coagulation and ristocetin cofactor activities
      are maintained above 50% in the postoperative critical period.

PMID- 1402172
TI  - [Cystic tumors of mediastinum].
AB  - Nine of twenty-four mediastinal tumors showed cystic lesions were operated at
      Kinki University Hospital. These nine mediastinal cysts included 5 of thymic
      cysts, 3 teratomas and one pericardial cyst. By the preoperative imagings, thymic
      cysts showed a smooth wall and homogenous content with water density. Teratoma
      consisted of cystic and solid parts, and the irregular thickness of the wall was
      found. One of these teratomas was ruptured into the pleural cavity, it has been
      proposed that digestive enzyme derived from pancreatic tissue with Langerhans
      island caused autolysis and necrosis with result in rupture. Pericardial cyst
      located at cardiophrenic angle mostly and which is useful on diagnosis.

PMID- 1402173
TI  - [The giant cavernous hemangioma of the neck].
AB  - A 67-year-old female who had complains of dyspnea and giant mass in the right
      neck. The plain CT scan and selective angiography showed an giant mass in the
      neck and extended into antero-superior mediastinum which pressed intrathoracic
      trachea. The tumor was resected completely by oblique neck incision and partial
      median sternotomy. It was 15 x 9 x 5 cm in size. The histological diagnosis was
      cavernous hemangioma. The giant cavernous hemangioma in neck extended into
      mediastinum is rare.

PMID- 1402174
TI  - [A case of idiopathic ventricular tachycardia with ventricular fibrillation
      successfully treated with cryoablations and implantable cardioverter
      defibrillator].
AB  - A 16-year-old girl with medically refractory idiopathic ventricular tachycardia
      (VT) with ventricular fibrillation (VF) underwent cryoablations of the VT origin
      and received implantable cardioverter defibrillator (ICD). Intraoperative
      epicardial and endocardial mapping demonstrated the earliest activation site of
      VT in the infundibular septum of right ventricle. Cryoablations were applied
      through a pulmonary arteriotomy under mild hypothermic cardiopulmonary bypass
      with the heart beating. Because of the episodes of VF. ICD implantation was
      followed. Her postoperative course was uneventful and she remains free from VT
      and VF.

PMID- 1402175
TI  - [Resection of tracheal carcinoma using partial cardiopulmonary bypass--report of
      a case].
AB  - A 43-year-old male was admitted to our hospital with chief complaints of stridor
      and dyspnea. Bronchoscopy revealed a tumor obstructing almost the whole lumen of
      the trachea. As it was impossible to insert an endotracheal tube into the distal
      site of the stenosis in the mediastinum, we used partial cardiopulmonary bypass
      to maintain gas exchange. The axillary artery and the femoral artery and vein
      were cannulated for the bypass using local anesthesia. During 105 minutes of
      bypass, the PaO2 value was good but the PaCO2 value increased up to 70 mmHg.
      After the trachea was opened, the anesthetic gas was administered across the
      operative field through the endotracheal tube and the cardiopulmonary bypass was
      discontinued. Tracheolaryngectomy and permanent tracheostomy with relocation to
      the right and caudal side of the brachiocephalic artery was performed
      successfully. The post operative course was very smooth. The patient has been
      well for 6 months since the surgery. Partial cardiopulmonary bypass proved to be
      useful for maintaining gas exchange during reconstructive surgery of the trachea.
      We treated a case of tracheal carcinoma by resection while using partial
      cardiopulmonary bypass. We believe this is the ninth such case reported Japanese
      literature.

PMID- 1402176
TI  - [An operated case of malignant localized mesothelioma of the pleura].
AB  - An operable case of pedunculated localized mesothelioma of the pleura, a 62-year
      old male, came to our clinic with chief complaint of chest X-ray abnormal shadow.
      On suspicion of pleural tumor, resection was performed. The operative findings
      revealed that the tumor was arising from visceral pleura of S1 + 2 a segment of
      left upper lobe, and didn't invade into peripheral tissue. The microscopic
      findings revealed that the tumor was consist of spindle tumor cells and capillary
      like lesions, and had high cellularity and many mitosis. The tumor was diagnosed
      as localized malignant mesothelioma. Immunohistochemical stainings were performed
      using six monoclonal antibodies, vimentin, CEA, EMA, keratin (AE1, AE3), Leu-M1.
      Only vimentin reacted with tumor cells.

PMID- 1402177
TI  - [Primary hemangiopericytoma of the chest wall--a case report].
AB  - An extremely rare case of a primary hemangiopericytoma of the chest wall was
      reported. A 40-year-old female without any complaints was detected to have an
      abnormal shadow in the right chest wall on a chest X-ray film. The tumor was 2.6
      x 2.2 x 2.0 cm in size and was resected together with the 8th rib which adhered
      to the tumor. Postoperative pathohistological examination led to the diagnosis of
      hemangiopericytoma. Postoperative course was uneventful, and the patient is now
      doing well and has had no recurrence for 11 months since the operation. A brief
      review was made on 9 cases collected from the literature.

PMID- 1402178
TI  - [Coarctation of aorta with right aortic arch and anomalous left subclavian
      artery].
AB  - The occurrence of coarctation in patients with right aortic arch is extremely
      rare. We have encountered a 21-year-old man with anomalous left subclavian
      artery. He was diagnosed when he was 13. On angiography he exhibited a right
      aortic arch. The left common carotid artery, right common carotid artery and the
      right subclavian artery diverged from the proximal side of the coarctation. The
      left subclavian artery diverged from the distal side. The right brachial arterial
      pressures measured 158-72 mmHg, while the left brachial arterial pressures
      measured 98-80 mmHg. Clinical studies revealed no vascular ring and no other
      anomalies were found in this patient. An attempt at treatment was made with extra
      anatomical bypass grafting from the ascending aorta to the descending aorta. No
      pressure difference due to coarctation remained after operation.

PMID- 1402179
TI  - [Pulmonary arteriovenous malformation with systemic blood supply].
AB  - A forty-eight year-old woman who had suffered from exertional dyspnea and
      cyanosis since her youth was found to have abnormal shadow in her right lower
      lung at the roentgenographic examination. Pulmonary angiography showed cavernous
      network between pulmonary artery and vein of the 8th, 9th, and 10th segments.
      Bronchial artery was dilated, supplying the cavernous lesion. From these findings
      this lesion was diagnosed as pulmonary arteriovenous malformation feeded by
      bronchial artery. Right lower lobectomy was performed. The effect of resection
      was confirmed by intraoperative arterial gas analysis before and after the
      excision. She has been doing well without any signs of recurrence for 3 years
      after the surgery.

PMID- 1402180
TI  - [Adjunctive methods during surgery for thoracoabdominal aneurysms--effect of
      selective visceral arteries perfusion incorporated with partial femoro-femoral
      bypass].
AB  - In this study, we report the effect of selective perfusion to the visceral
      arteries during aortic cross-clamping at surgery for thoracoabdominal aortic
      aneurysms with an adjunct of femoro-femoral (F-F) extracorporeal bypass. The
      total series comprising 28 patients were divided into 3 groups according to the
      perfusion mode to the celiac and the renal arteries, i.e., group I; the arteries
      were continuously perfused by the extracorporeal bypass, group II; aortic cross
      clamp excluded the branches from the bypass flow but selective perfusion was
      employed, and group III; the liver or the kidneys were subjected to ischemia. As
      a result, group III developed hepatic failure at the incidence of 50% which was
      characterized by hepatocellular damage followed by cholestatic dysfunction. As
      for postoperative renal function, this group revealed persistently high level of
      serum creatinine, and 60% of this series resulted in renal failure. On the
      contrary, group II showed a comparable effect to group I on the preservation of
      hepato-renal function, and there were no differences in the incidence of hepatic
      or renal failure between the two groups. Multiple organ failure was a predominant
      cause of hospital death, and it developed only in the cases with aortic cross
      clamp time more than 90 minutes. However, avoiding ischemia achieved in group I
      or II significantly reduced the incidence of MOF and its related deaths. It is
      concluded that selective perfusion system incorporated with an aid of F-F partial
      bypass was a useful measure to protect vulnerable organs from ischemia and to
      reduce postoperative mortality and morbidities.

PMID- 1402181
TI  - [Two-stage Jatene procedure after Mustard or Senning operation].
AB  - We have successfully performed a two-stage Jatene procedure in four patients who
      showed severe anatomical right ventricular dysfunction after atrial switch
      (Mustard or Senning) operation for transposition of the great arteries. All four
      patients developed an adequate left ventricular pressure for the arterial switch
      operation by one or two-stage pulmonary artery banding. Left ventricular
      posterior wall thickness increased sufficiently enough after the banding although
      left ventricular ejection fraction showed significant decrease. After Jatene
      procedure left ventricular ejection fraction recovered, and RV end-diastolic
      volume which had been prominently enlarged preoperatively was dramatically
      normalized. Cardiac index increased from 3.6 +/- 1.6 l/min/m2 preoperatively to
      5.3 +/- 6.1 l/min/m2 postoperatively with the decrease in left atrial pressure.
      Postoperative electrophysiological study revealed the recovery of sinus node
      function and atrial conduction by means of the take-down of atrial switch
      operation previously performed. We conclude that the Jatene procedure should be
      an ideal alternative in patients with right ventricular dysfunction after atrial
      switch operation. The left ventricle could be prepared by an effective pulmonary
      artery banding in most instances.

PMID- 1402182
TI  - [Long-term results of the Blalock-Taussig shunts].
AB  - One-hundred and thirty-six patients received the classical Blalock-Taussig shunts
      between 1980 and 1990. Their age range at operation was 4 days to 12.8 years and
      their median age was 13 months. The operative mortality rate was 0.7% (1/136).
      The survivors were followed up from 1 month to 11.5 years, 5.4 years in average.
      Twenty-five patients required another shunt and the mean interval to that
      procedure was 2.4 years (modified Blalock-Taussig 23, classical Blalock-Taussig
      2, Glenn 1, internal mammary artery-pulmonary artery shunt 1). Forty-five
      patients received corrective operations, there were four operative deaths (Fontan
      2, Rastelli 2). There were 15 late deaths of which three deaths were not
      cardiogenic. One year after operation, 91.0% of patients remained in well
      palliated condition. At three years after operation, 76.4% of patients continued
      to be in well-palliated condition. There were twelve neonates in this series.
      Their age range was 4 to 26 days and their median age was 13 days. There was no
      operative death. Five patients required second shunt. There were two late deaths.
      At present, six patients continue to be in well-palliated condition 8 months to 9
      years after first operation. Angiographic findings showed the stenotic change of
      the vascular anastomoses in 49.3% (35/71) of patients. This study suggests that
      polydioxanone suture (PDS) will be useful for the growth of the anastomoses in
      Blalock-Taussig operation.

PMID- 1402184
TI  - [Glucose tolerance and insulin secretion in infants with the left to right shunt
      congenital heart disease].
AB  - Between 1980 and 1988, 32 infants under three years of age with left to right
      shunt congenital heart disease underwent cardiac catheterizations, and their
      glucose tolerance and insulin secretion were investigated. These patients were
      divided into three groups by weight and compared. Group I consisted of 11
      patients whose weights were 80% or more of the ideal body weight (IBW) for their
      age. Group II consisted of 10 patients whose weights were between 70% and 80% of
      the IBW. Group III consisted of 11 patients whose weights were less than 70% of
      the IBW. The CTR and biochemical blood studies showed no difference. By cardiac
      catheterization, Group III showed higher pulmonary/systemic vascular pressure
      ratio (Pp/Ps) than Group I. The mixed venous O2 saturation (SvO2) were 69.5 +/-
      6.41% in Group I, 64.8 +/- 5.78% in Group II, 57.2 +/- 3.59% in Group III. Group
      III showed the lowest SvO2 of the three. Group III also showed the lowest
      arterial O2 saturation (SaO2). This indicates that the patients of Group III had
      the most serious congestive heart failure. In the 0.5 g/kg intravenous glucose
      tolerance tests, the K values (glucose disappearance rates) were as follows:
      Group I: 3.30 +/- 0.597, Group II: 2.91 +/- 0.624, Group III: 2.48 +/- 0.417.
      Group III showed the lowest values of the three. This indicates the deterioration
      of glucose tolerance in Group III. In the examination of serum insulin secretion,
      Group III showed the lowest serum insulin levels: 26.6 +/- 18.3 mmu/ml at 3
      minute intervals, 22.8 +/- 14.3 mmu/ml at 5-minute intervals. After cardiac
      catheterization, corrective operations were performed on 17 patients out of 32.
      Fifteen patients survived, though 2 patients of Group III died early
      postoperatively. The results of glucose tolerance test and serum insulin levels
      before and after operation in 12 survivors were compared. Although the K values
      had been 2.8 +/- 0.41 before operation, it rose up to 3.81 +/- 0.81 three to four
      weeks after operation. The serum insulin levels at 3, 5, 10 and 15-minute
      intervals also rose after operation. This indicates the improvement of glucose
      tolerance and insulin secretion due to the improved circulation. It is suggested
      that the adequate nutritional management before and after operation on infants
      with serious congestive heart failure, because they tend to have malnutrition
      before operation. Aggressive and careful nutritional management is advisable.

PMID- 1402183
TI  - [Management of type A acute aortic dissection--results of the cases with
      thrombosed false lumen].
AB  - By reviewing the outcome, we studied the propriety of our principles for the
      treatment of type A acute aortic dissection in 45 patients, encountered during
      the 10-year period between 1981 and 1990. We conducted a comparative study of
      patients with a thrombosed false lumen (type T) and a patent false lumen (type P)
      to examine the effect of an acutely thrombosed false lumen on the prognosis of
      this disease. For the 25 patients treated in the first 6 years (1981-1986),
      operation was performed as soon as exact diagnosis was made, regardless of the
      presence of complications and the type or severity of the disease. Early death
      occurred in 9/20 operated cases and in 4/5 unoperated cases, so 13/25 patients
      died for a 52.0% mortality rate. For the 20 patients who received treatment in
      the latter period (1987-1990), we gave priority to conservative treatment for
      type T cases that were free from complications, and adopted a treatment method
      attaching greater importance to the resection of intimal tears. As a results,
      early deaths were observed in only 4 type P patients (20.0%) who underwent
      operation, a significant better result (p < 0.05). For patients in whom we were
      able to excise the intimal tear (30.0%, early mortality rate), the results were
      better than in those in whom the intimal tear were left alone (53.8%). The
      results were particularly good in type T patients (25.0% of them underwent
      intimal tear resection and 71.4% underwent no operation for the intimal
      tear).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402185
TI  - [Changes in left ventricular function during exercise after lung resection--study
      with a nuclear stethoscope].
AB  - In 29 cases undergoing lung resection, effects of the surgery on left ventricular
      function were investigated indirectly with a Nuclear Stethoscope. Various
      parameters were measured following an exercise load before and after surgery.
      There were significant decreases in post-operative resting levels of stroke
      volume (SV) (p < 0.001), end-diastolic volume (EDV) (p < 0.001), ejection
      fraction (EF) (p < 0.05) and ejection rate (ER) (p < 0.001) and significant
      increase in heart rate (HR) (p < 0.001) when compared to pre-operative resting
      levels. Neither filling rate (FR) nor cardiac output (CO) showed significant
      difference. At maximum exercise load, there were significant decreases in post
      operative EDV (p < 0.005), SV (p < 0.005), ER (p < 0.001) and FR (p < 0.005), but
      no significant differences were detected in HR and EF; consequently, there was a
      significant decrease in CO (p < 0.005). Ratio of the levels at maximum load to
      those at resting of each parameter did not show significant difference between
      before and after operation with regard to any parameters except CO and FR which
      showed significant decrease (p < 0.005 and p < 0.001, respectively). Effects of
      the surgery on left ventricular function were studied according to amount of lung
      resection. In 13 cases where more than two lobes were resected, similar
      significant differences to those mentioned above were found in all parameters
      except EF. In cases where a single lobe was resected, only ER and FR showed
      similar tendency to that described above. Effects of the surgery on left
      ventricular function were also studied according to age of patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1402186
TI  - [Analysis of the determinant factors for open heart surgery without blood
      transfusion by the quantification theory--possibility of application of maximum
      surgical blood order schedule for open heart surgery].
AB  - In order to complete operations without blood transfusion we have chosen means of
      preoperative autologous blood saving and intraoperative autotransfusion, but we
      have not always achieved our purpose. We examined 29 patients (13 patients
      without blood transfusion and 16 with blood transfusion) to analyze the
      determinant factors as to whether open heart surgery without blood transfusion
      may be indicated or not, according to the quantification theory (type II) and to
      examine the possibility to apply the maximum surgical blood order schedule
      (MSBOS) for the open heart surgery by the quantification theory (type I). The
      analysis of determinant factors revealed hematocrit (Ht) value before saving of
      blood (more than 40%) as the best contributor of possibility of non-blood
      transfusion surgery, followed by the amount of blood loss during operation (less
      than 600 ml), the amount of saving blood (more than 800 ml), body weight (less
      than 70 kg), calculated Ht value on the beginning of cardiopulmonary bypass (CPB)
      (more than 24%), CPB time (less than 120 minutes) and the amount of postoperative
      blood loss (less than 600 ml). The prospective using blood volume at the
      operation was precisely calculated by the values of 4 preoperative factors, that
      is, the amount of saving blood, calculated Ht value on the beginning of CPB, CPB
      time and body weight. Therefore it is important to increase the amount of
      preoperative saving blood and decrease the amount of surgical bleeding in order
      to perform operations without blood transfusion, and is possible to apply the
      MSBOS for the open heart surgery.

PMID- 1402188
TI  - [Coronary revascularization with arterial graft alone].
AB  - In the period from December 1989 until July 1991, coronary revascularization were
      performed on 56 patients using arterial grafts and no venous grafts. The ages of
      the patients ranged from 43 to 85 years (average; 66.8 years), and there were 33
      males and 23 females. Twenty-four patients had angina pectoris, 23 had old
      myocardial infarction and 9 had acute infarction. There were 3 patients with
      single-vessel coronary disease, 19 with double-vessel, 31 with triple-vessel and
      9 with left main coronary disease. The bypass grafts used were 58 left internal
      thoracic artery (LITA) grafts, 29 right internal thoracic artery (RITA) grafts,
      and 56 right gastroepiploic artery (RGEA) grafts. Thus, 143 grafts were used and
      an average of 2.6 bypasses were created per patient. There were two operative
      deaths. One of these patients had acute myocardial infarct. Investigation of
      postoperative graft patency was performed in the 122 grafts that could be
      examined angiographically after surgery. Only 7 were obstructed, yielding a
      patency rate of 94.3%. By using both the ITA and RGEA, in situ anastomoses with
      all the coronary arteries could be performed. Also in emergency surgery arterial
      grafting was possible. This operative form is considered to be a useful technique
      and may be expected to produce favorable long-term results.

PMID- 1402187
TI  - [An assessment of the separation of mediastinal lymph nodes by preoperative
      mediastinoscopic examination as a dissecting measure in the surgical treatment of
      lung cancer].
AB  - The availability of the separation of mediastinal lymph nodes by preoperative
      mediastinoscopic examination as a dissecting measure was analyzed according to
      prognosis retrospectively because mediastinal lymph nodes dissection is made with
      ease and certainty after the examination. The separation by mediastinoscopic
      examination did not have an impact on the mediastinal lymph nodes dissection for
      carcinoma of the left lung and superior mediastinal lymph nodes metastases (# 1
      4), but an influence on the dissection for carcinoma of the right lung and middle
      and lower mediastinal lymph nodes metastases (# 5-9). This result showed the
      existence of occult metastases and the good effects caused by the separation of
      mediastinal lymph nodes. In the histological type, the effects were present in
      squamous cell carcinoma and p-N0 adenocarcinoma, but it was concluded that the
      prognosis in adenocarcinoma was associated with other factors rather than lymph
      node metastasis. Therefore, it can be seen that the separation of mediastinal
      lymph nodes by preoperative mediastinoscopic examination is available as a
      dissecting measure.

PMID- 1402189
TI  - [A case of leiomyoma of the chest wall].
AB  - A case report of a leiomyoma of the chest wall is presented. So far as we
      examined, this is the first case of the leiomyoma of the chest wall in Japan. A
      40-year-old woman was admitted to our hospital because of an abnormal shadow in
      the right upper lung area in a chest X-ray film. The thoracic CT and MRI
      demonstrated a tumor of the chest wall projecting into the thoracic cavity. The
      tumor was excised. Histological examination indicated that the tumor was a benign
      leiomyoma. This tumor seems to originate from the wall of the small vessels
      histologically. The patient's postoperative course is uneventful.

PMID- 1402190
TI  - [A case of acute A type aortic dissection with lower extremity ischemia-
      percutaneous fenestration of the aortic septum followed by ascending aortic graft
      replacement by open distal anastomosis and retrograde cerebral perfusion].
AB  - A 56-year-old woman with severe back pain and a cold, pulseless right extremity
      was admitted to our hospital. Angiogram revealed a type A aortic dissection
      extending from ascending aorta to the aortic bifurcation with no definite re
      entry point. The false lumen gave origin to the right renal artery and the right
      external iliac artery was occluded. Therefore, a catheter was manipulated into
      the true lumen through a percutaneous right femoral artery approach, and was
      advanced into the false lumen through the right posterolateral wall of the
      dissecting aortic septum. Fenestration was then performed with fully dilated
      angioplasty balloon across the septum. Immediately after the procedure, the
      patient's symptoms improved. The day after the fenestration, replacement of the
      ascending aorta with 24 mm woven Dacron graft was followed under the deep
      hypothermia and the retrograde cerebral perfusion. The patient followed a
      satisfactory postoperative course and postoperative angiogram showed a complete
      closure of the entry at the ascending aorta and adequate revascularization of the
      right renal and external iliac arteries.

PMID- 1402191
TI  - [A successful transatrial repair of post-infarction ventricular septal defect].
AB  - A 63-year-male underwent successful operation for the ventricular septal
      perforation (VSP) caused by the inferior myocardial infarction. As the condition
      was stable, an operation was performed at the 43rd day after onset of myocardial
      infarction. Exposure was obtained by the opening the right atrium and retracting
      the tricuspid valve. The defect was in the posterior portion of the ventricular
      septum and closed using a Dacron patch. His postoperative course was uneventful.
      Postoperative examinations show no residual shunt. We believe that this approach
      may offer reduced mortality and morbidity in a selected group of patients with
      acquired posterior VSP, by avoiding such complications as further trauma to the
      ventricle, hemorrhage, and arrhythmias.

PMID- 1402192
TI  - [Successful surgical treatment of coronary aneurysm following PTCA].
AB  - A case of 50-year-old man who developed coronary aneurysm at the initial PTCA
      site following dilatation was reported. The patient was suffered severe effort
      angina pectoris and admitted to our hospital. Coronary angiography revealed 99%
      stenosis in the right coronary artery (RCA), and the underwent balloon dilatation
      of the RCA lesion with 3.0 mm balloon catheter at 3 atm of pressure. PTCA
      provided sufficient coronary dilatation, however a small dissection remained. He
      was discharged from the hospital without any symptom. Two months after PTCA he
      was suffered from recurrent angina, and electrocardiographic exercise stress test
      was positive for ST segment depression in inferior wall. The repeat coronary
      angiography showed severe stenosis of the original lesion and aneurysm formation
      at the area of dissection which occurred during initial angioplasty. Coronary
      artery bypass surgery with a saphenous vein graft performed successfully.

PMID- 1402193
TI  - [A case of superficial esophageal carcinoma with remarkable changes in appearance
      on endoscopy].
AB  - Iodine staining and biopsy has been utilized in the endoscopic examination of
      superficial esophageal carcinoma. 59-year-old male was occasionally revealed to
      have esophageal carcinoma. There existed 0-IIb type superficial esophageal
      carcinoma in 1/3 circulation on the first endoscopic study. After 3 weeks, only
      erosive change of 5 mm in diameter could be observed. In the microscopic study of
      the resected specimen, there were phagocyte infiltration, epithelial cell
      ballooning, and remnant carcinoma cells in only basal layer. It was suggested
      that epithelium had desquamated and regenerated with extrinsic stimulation,
      therefore its appearance changes remarkably.

PMID- 1402194
TI  - [An adult case of dyspnea and overinflation of the residual lung with
      disappearance of the postpneumonectomy space after left pneumonectomy].
AB  - Mediastinal shift and overinflation of the residual lung after pneumonectomy are
      well known, and sometimes cause pulmonary insufficiency. However, most of such
      cases occur after surgery in childhood or adolescence. We present a 49-year-old
      woman who had dyspnea and severe overinflation of the residual lung after left
      pneumonectomy. She had undergone pneumonectomy at the age of 33 years. Dyspnea on
      exertion occurred 4 years later, and became much more severe 9 years later (H-J
      IV degrees). Computed tomography showed that the postpneumonectomy space and
      completely disappeared and the right lung was overinflated to the left posterior
      axillary line. Low vital capacity with high residual volume and low maximal
      ventilatory volume were detected by pulmonary function test. Pulmonary function
      after pneumonectomy is difficult to predict because mediastinal shift and
      overinflation of the residual lung may occur. To avoid this, prosthesis plombage
      for the postpneumonectomy space is necessary.

PMID- 1402195
TI  - [A case report--combined Jatene procedure and extended aortic arch reconstruction
      for the original Taussig-Bing malformation associated with hypoplastic aortic
      arch, subaortic stenosis and coarctation of the aorta].
AB  - A successful repair with combined Jatene procedure (Lecompte modification) and
      extended aortic arch reconstruction in a two-month-old boy with the original
      Taussig-Bing malformation, associated with hypoplastic aortic arch, subaortic
      stenosis and coarctation of the aorta was described. The ascending aorta was
      measuring 8 mm and the distal aortic arch was 4 mm in outer diameter. The
      interventricular rerouting was not feasible, because the infundibular septum was
      almost aligned to the interventricular septum. So that arterial switch operation
      was preferred. The primary interventricular foramen was enlarged by wedge
      resection and the secondary interventricular foramen was closed with a patch of
      preserved equire pericardium. An extensive patch angioplasty of entire aortic
      arch down to descending aorta was performed with a composite patch of Xenomedica
      (preserved equire pericardium) and Dacron velour. Hypertrophied muscle bundles
      were resected for relief of subaortic stenosis. Jatene procedure was then
      performed. During neo-pulmonary reconstruction, distal pulmonary orifice was
      shifted towards right to avoid kinking and compression on the coronary arteries.
      One stage correction consisting of Jatene procedure and extended aortic arch
      reconstruction was considered to be a procedure of choice in this type of complex
      anomalies.

PMID- 1402196
TI  - [A case of infective endocarditis with multiple embolic complications].
AB  - A 13-year-old girl was admitted to a hospital because of fever and sore throat.
      Staphylococcus aureus was obtained on blood culture, and she was treated with
      antibiotics under the diagnosis of sepsis and DIC. Echocardiography showed huge
      vegetation attached to the posterior leaflet of mitral valve and severe mitral
      regurgitation. CT scan revealed multiple heterogeneous high density areas in her
      brain. She was transferred to our hospital for further examination and treatment.
      Large verrucae on the mitral valve, severe regurgitation and repeated embolism
      urged us to the emergency mitral valve replacement. Debridement of abscess on the
      posterior wall of the left atrium and ventricle necessitated patch plasty of
      those structures and mitral ring as well. Operative and postoperative examination
      showed mycotic aneurysm of right coronary artery, multiple brain hemorrhage,
      arterial obstructions of extremities and splenic infarction. Sooner she recovered
      except for slight macular degeneration caused by retinal embolism.

PMID- 1402197
TI  - [A case report of spinal epidural hematoma complicated after open heart surgery].
AB  - The authors reported the first case of acute spinal epidural hematoma (SEH)
      developed after open heart surgery. The patient was noticed that her legs felt
      weak and numb on the first postoperative day evening. On the next day morning,
      neurological examination revealed that flaccid paralysis of both legs and also
      loss of all sensory perception below the level of Th-6 spine bilaterally. The
      prolonged effect of anesthesia and painless onset made delayed recognition of the
      lesion. SEH (Th5-7) was diagnosed with MRI and decompressive surgery was
      immediately done, sixty hours after the beginning of cardiac operation. But in
      this case neurological deficits were not changed. We concluded that a routine
      diagnostic approach was very important procedure to find out this serious
      complication for all patients underwent open heart surgery in early period of its
      onset.

PMID- 1402198
TI  - [A case of acute right ventricular infarction and life-saving right ventricular
      assistance following emergency coronary revascularization and resection of a left
      ventricular aneurysm--discussion of indication and proper assist flow volume].
AB  - Right ventricular assistance (RVA) using centrifugal pump in combination with
      IABP was used to treat a patient who was difficult to wean from a cardiopulmonary
      bypass following emergency coronary revascularization and resection of a
      ventricular aneurysm performed to treat acute right ventricular infarction due to
      a PTCA complication. After 131 hours of RVA at 3.2 to 4.8 l/min, it was possible
      to remove the pump. No heparin was administered during this time, changing the
      pump head twice, was used for 64 and 50 hour period, no thrombi were detected
      either time. After being weaned from RVA, the patient developed severe
      respiratory dysfunction, but on the 10th postoperative day (POD) IABP was weaned,
      and on the 13th POD the artificial respirator was withdrawn. The results of the
      postoperative cardiac catheterization were favorable, the patient was discharged
      on the 57th POD, and has returned to society at the present time. The indications
      for RVA include a central venous pressure > 20 mmHg and a cardiac index < 1.8
      l/min/m2, and tissue perfusion pressure and general preoperative condition should
      severe as guides. The higher the assisted flow volume the more efficacious in
      relieving ventricular load, but, since there is a limit to how much the left
      ventricle and lungs can withstand, it should not exceed levels which ensure the
      maintainance of cardiac output and tissue perfusion pressure.

PMID- 1402199
TI  - [A case report of translocation method for active infective aortic valve
      endocarditis with aortic root abscesses].
AB  - We experienced a case of 51-year-old woman who underwent emergency aortic valve
      replacement by translocation method for active infective aortic valve
      endocarditis with aortic root abscesses. Postoperative course was complicated as
      the following. Three days later, the perforation of noncoronary sinus of Valsalva
      into the right atrium was noted and she developed progressive heart failure due
      to the massive left-to-right shunt. The second operation was performed
      immediately for the patch closure of the perforation through the right atriotomy.
      Two months later, unstable angina appeared because of the stenosis of the vein
      graft to the left coronary artery, leading to the emergency third operation in
      which LITA was placed to the left anterior descending artery. In spite of these
      complications she recovered gradually and she was discharged 6 months after the
      first operation. She is now doing well in NYHA class 2. Translocation method is
      quite useful for such a case of the aortic valve endocarditis with periannular
      abscesses in whom conventional valve replacement is supposed to be impossible,
      but the long durability of this type of the repair is unknown. Careful follow-up
      of the patient is mandatory.

PMID- 1402200
TI  - [Two cases of post-thymectomy myasthenia gravis].
AB  - The first patient was a 37-year-old man with an invasive and lymphoid cell
      dominant thymoma (stage III). He underwent extended total thymectomy and partial
      resection of the upper lobe of the left lung. Four years after the operation, he
      had ptosis and diplopia and was diagnosed as having myasthenia gravis (positive
      Tensilon test and raised antiacetylcholine receptor antibody titer). His symptoms
      improved with the steroid therapy. The second patient was a 37-year-old woman
      with an invasive and mixed type thymoma (stage III). Extended total thymectomy
      with combined resection of the mediastinal pleura and right phrenic nerve was
      performed, but the tumor recurred in the right thorax 2 years postoperatively.
      Subtotal resection of the parietal pleura and recurrent tumors was performed by
      right thoracotomy, and steroid therapy was given. She developed malaise, ptosis
      and diplopia three months later, and was diagnosed as having myasthenia gravis.
      Her symptoms disappeared after the steroid therapy was stopped. A review of the
      Japanese literature is presented and problems regarding the pathogenesis of this
      disease are discussed.

PMID- 1402201
TI  - [Aortic arch and descending aortic replacement under deep hypothermia and
      circulatory arrest through left thoracotomy--case report].
AB  - Graft replacement of the transverse aortic arch and the descending thoracic aorta
      was done for two cases with Stanford type B aortic dissection involving the
      aortic arch. Cardiopulmonary bypass was established with left atrium and femoral
      vein for venous line and femoral artery for arterial line. Patients were cooled
      until their EEG activity had disappeared, then the bypass was discontinued.
      Lesser curvature of the transverse aortic arch was resected and graft was sutured
      by beveled fashion. After reinstitution of the bypass, intercostal arteries (Th8
      10) were reattached to the graft and distal anastomosis was made above the
      diaphragma. Postoperative recovery was uneventful in both cases.

PMID- 1402202
TI  - [A case of squamous cell carcinoma of the lung treated by right sleeve upper
      lobectomy after photodynamic therapy].
AB  - This patient, a 62-year-old female, with squamous cell carcinoma of the lung was
      inoperable because of poor pulmonary function due to severe bronchial stenosis by
      a tumor at the orifice of the right main bronchus. As the tumor decreased in size
      after photodynamic therapy (PDT), the bronchial stenosis decreased and her
      pulmonary function improved sufficiency to permit surgery. When right upper
      sleeve lobectomy was performed, only limited peribronchial inflammation related
      to PDT procedure was detected indicating only slight extrabronchial influence of
      PDT. This suggests that PDT is a viable adjunct modality in case in which surgery
      might possible be performed. The patient has a good postoperative course and is
      alive 18 months after surgery without any evidence of recurrence.

PMID- 1402203
TI  - [A case report of well differentiated fetal adenocarcinoma].
AB  - A 32-year-old female, who was admitted with complaints of cough and an abnormal
      shadow in the left lower lobe, was diagnosed as adenocarcinoma of the lung by
      TBLB. She underwent left lower lobectomy and lymph node dissection.
      Histopathological findings showed well differentiated fetal adenocarcinoma
      (WDFA). Well differentiated fetal adenocarcinomas are considered to have a
      histogenesis similar to that of pulmonary blastoma and may be a tumor with one
      sided development of pulmonary blastoma showing only an epithelial component.

PMID- 1402204
TI  - [A case of primary acinic cell tumor of the trachea].
AB  - A 62-year-old woman complained cough and hemosputum. Chest X-ray film and
      thoracic computed tomography revealed tumor shadow, localizing in the upper
      trachea, measuring 2 x 1 cm. Through a median sternotomy, resection of the
      trachea of 4 cartilagous rings was made, followed by end-to-end anastomosis.
      Fixing of tracheal anastomosis was performed for 2 weeks using SOMI brace. The
      size of tumor was 1.3 cm in diameter. Histologically, nodular tumor foci were
      seen close to the normal trachea gland, localing in tracheal mucosa. Tumor cells
      with basophilic cytoplasma developed acinical structure. Postoperative course was
      uneventful. This patient is alive 42 months after resection. This disease is
      extremely rare, we have found only 4 reported cases including our case in the
      world literature and only 2 cases in the Japanese literature.

PMID- 1402205
TI  - [Left ventricular approach for muscular ventricular septal defects in infant].
AB  - Two infants less than 4 months of age underwent repair of apical muscular VSD
      with left ventriculotomy. First case was 3 months old boy who had already
      undergone enlargement of the hypoplastic aortic arch with subclavian flap
      aortoplasty and pulmonary artery banding because of the associated aortic
      coarctation. Second case was 4 months old Down syndrome girl who associated with
      ASD and PDA. Both infants were diagnosed the apical muscular VSD with
      echocardiography and left ventriculography. We performed short longitudinal left
      ventriculotomy which was parallel to the left anterior descending coronary artery
      between the diagonal branch and left circumflex artery. VSD was closed with Gore
      Tex patch using 6-0 prolene buttress stitches. Post operative echocardiography
      showed good LV contractile function (Ejection Fraction = 71%, 80%), and no
      residual interventricular shunt. Left ventriculotomy for the apical VSD closure
      allowed good exposure and did not reduce the LV function even in infants.
      Therefore, we concluded that left ventriculotomy was an useful procedure for the
      apical muscular VSD in infants.

PMID- 1402206
TI  - [The 45th General Meeting of the Japanese Society for Thoracic Surgery. Niigata,
      Japan, October 14-16, 1992. Abstracts].

PMID- 1402207
TI  - [Molecular mechanism of the import of mitochondrial protein precursors].

PMID- 1402208
TI  - [Regulation of gene expression in the early development of sea urchin embryos].

PMID- 1402209
TI  - [Structure and development of pepsinogens].

PMID- 1402210
TI  - [Structures and biological activities of heparin-like molecules].

PMID- 1402211
TI  - [Metabolism of purine nucleotides in plants].

PMID- 1402212
TI  - [Peptides and proteins containing a D-amino acid residue from the animal
      tissues].

PMID- 1402213
TI  - Indobufen vs acetylsalicylic acid plus dipyridamole in long-term patency after
      femoropopliteal bypass.
AB  - To compare the effects of indobufen (INB) with those of ASA+dipyridamole (DP) on
      graft patency, 113 patients undergoing femoropopliteal bypass surgery were
      randomly and blindly assigned to treatment with INB 400 mg daily or with ASA 900
      mg daily plus DP 225 mg daily. Treatment started 2 days before surgery and lasted
      for 12 months. All patients underwent two angiographic examinations: the first
      early after surgery (mean 6 days) and the second at the end of the study (mean
      368 days). The 1 year cumulative patency rate for INB was 60% higher but not
      statistically different from the ASA-DP group (53.2%). The relative risk
      (INB/ASA+DP) calculated by the Mantel-Haenszel test was 0.86 (confidence limits
      0.54-1.35). Only the site of operation (above-knee or below-knee) has a
      significant prognostic value on the fate of the graft.

PMID- 1402214
TI  - Interaction between vascular prostheses and rifampicin in the prevention of the
      grafts infection. An experimental study.
AB  - Infections caused by synthetic prostheses are relatively rare (1.5-6%) but
      serious complication in vascular surgery. There is no doubt that during and
      immediately after surgery bacterial contamination may occur. An in vitro study
      was carried out in the Vascutek laboratories, which revealed a high affinity
      between prostheses in Dacron gel and Rifampicin. This affinity, the result of an
      ionic bond, was demonstrated by the fact that after 5 days Rifampicin was still
      present on the prostheses. Encouraged by this result, an experimental study was
      carried out in sheep. Five sheep were operated on making a prosthetic graft in
      both of the common carotid arteries: on one side a Gelseal Dacron prosthesis was
      implanted after being soaked for 15 minutes in a solution containing 1 mg/ml
      Rifampicin. A Knitted Dacron prosthesis was implanted in the contralateral
      carotid artery, again after pretreatment with Rifampicin. Explants were made
      after 2, 24, 48, 72 and 96 hours, and the concentration of Rifampicin on the
      prostheses was assessed on the basis of the diameter of the inhibition area on
      Staphylococcus aureus cultures. The results showed that the Gelseal Dacron
      prostheses maintained Rifampicin concentrations with an antibacterial activity up
      to 72 hours; this property disappears with the Knitted Dacron prostheses after
      only 24 hours. These results confirm the high affinity of Gelseal Dacron and
      Rifampicin also in in vivo experimental models.

PMID- 1402216
TI  - Plethysmographic findings in normal subjects using a capacitance mode.
AB  - A new strain-gauge plethysmographic system, Phlebotest, was evaluated in 19
      normal subjects, yielding 38 lower limbs for study. A capacitance mode was used
      which allowed both the left and right calves to reach their maximal volume
      expansion before releasing the cuff pressure (60 mmHg in this study). Parameters
      such as the maximum volume change (V sec), the outflow rate during the first
      second after deflation (F 1.0), the expelled volume in four seconds (EV 4.0) and
      the surface area over the curve during the first four seconds after deflation
      (IND) were automatically calculated and their side differences between the left
      and right legs were determined respectively. There was a good linear correlation
      between EV 4.0 and V sec (r = 0.9274, p less than 0.0005) and the EV 4.0/V sec
      ratio was calculated. In contrast to the previous reports, between three
      consecutive determinations there were no significant differences in the
      measurements of these parameters, and V sec consistently kept an identical mean
      value. These results suggest that using this new system only one determination of
      calf expansion is required. The reason might be that, in addition to some
      technical improvements, the computer-controlled capacitance function can secure
      the optimal venous filling in every determination.

PMID- 1402215
TI  - Cerebral SPECT with 99mTc-HMPAO in extracranial carotid pathology: evaluation of
      changes in the ischemic area after carotid endarterectomy.
AB  - The authors report their experience in studying patients undergoing carotid
      endarterectomy with simple photon emission computed tomography (SPECT). This
      technique made it possible to identify areas of preoperative cerebral
      hypoperfusion in 54.8% of the patients which had a good correlation with
      neurological symptoms. To distinguish gradual changes in the ischemic lesions, a
      method of assessing the surface of the hypoperfused areas was adopted. In
      addition, SPECT made it possible to detect a greater number of hypoperfused areas
      even in sites other than those revealed by CT. Moreover, there was good
      correlations between the SPECT data and the grade and site of the carotid lesion
      and the data provided by some intraoperative monitoring procedures. The Authors
      therefore propose the use of SPECT in the evaluation of patients with
      cerebrovascular insufficiency following a carotid disease.

PMID- 1402217
TI  - Hypertensive ischemic leg ulcer (Martorell's ulcer): a specific disease entity?
AB  - Histology of seven clinically diagnosed cases of Martorell's ulcer was compared
      with that of twenty-seven crural ulcers of venous origin. Although the majority
      of Martorell's ulcers are accompanied by a longstanding hypertension with
      markedly elevated diastolic pressure values, the conception of a specific disease
      entity with a common etiology should be abandoned. Some of the cases may be due
      to hypertension alone, but others may be caused or at least enhanced by other
      microvascular disorders.

PMID- 1402218
TI  - Partial regression of vascular structural alterations in hypertensive patients
      treated with alpha-beta-blocker, labetalol.
AB  - We studied the structural and functional characteristics of the vascular bed at
      calf level in 46 middle aged hypertensive patients (20 males and 26 females)
      treated with different beta-blockers. After one week of placebo, the patients
      were divided into three groups: group 1 was treated with labetalol, an alpha-beta
      blocker (200 mg t.t.d.); group 2 was treated with acebutolol, a cardioselective
      beta-blocker with intrinsic sympathomimetic activity (ISA) (200 mg t.t.d.); group
      2 was treated with acebutolol, a cardioselective beta-blocker with intrinsic
      sympathomimetic activity (ISA) (200 mg t.t.d.); group 3 was treated with
      metoprolol, a cardioselective beta-blocker without ISA (100 mg t.t.d.). Before
      and after placebo, and after three months of active drug treatment, we measured
      blood pressure, and rest and peak flow at the calf level by strain gauge
      plethysmography. Basal and minimal vascular resistances were calculated as the
      ratio between mean blood pressure and rest or peak flow, respectively. A
      significant decrease in blood pressure was observed in each group. However, basal
      and minimal vascular resistances decreased only in the labetalol-treated group.
      These observations indicate that antihypertensive agents that have similar
      effects on blood pressure, may have different effects on minimal vascular
      resistance. Therefore, maximum vasodilation of arterioles improves, suggesting
      that long term treatment with labetalol, but not with other beta-blockers is able
      to induce a partial regression of vascular structural alterations in hypertensive
      patients.

PMID- 1402220
TI  - Are the ultrasonic imaging technics (duplex or triplex) alone sufficient for
      decision-making in carotid endarterectomy? Pros and cons.

PMID- 1402219
TI  - Acute rupture of an aortic aneurysm mimicking the discus hernia syndrome. A case
      report.
AB  - Aneurysms of the abdominal aorta have been recognised as a cause of back pain and
      vertebral erosion. However back pain and paraplegia are uncommon, presenting
      complaints in patients with aortic aneurysms. A case of acute rupture of an
      abdominal aortic aneurysm is presented mimicking the symptoms of a discus hernia
      syndrome and paraplegia.

PMID- 1402221
TI  - Results of femoropopliteal and femorotibial greater saphenous vein in situ
      bypass. Life table analysis.
AB  - Five-hundred-ninety-four nonselected "in situ" reconstructions were analysed
      retrospectively using the life table method. Especially after immediate occlusion
      cumulative patency is very unsatisfactory. After 5 years cumulative patency rate
      in these cases is 39.5% vs. 64.9% in all cases. Patency rates are influenced by
      the anastomotic site and the run-off quality. While statistically not
      significant, popliteal anastomoses perform a little better after 5 years than
      peripheral anastomoses (67% vs. 51% cumulative patency rate). The number of
      patent tibial arteries seems to be the most important determinant. In non
      occluded run-off cases (three patent tibial vessels) the cumulative patency rate
      after 5 years is 82.2% vs. 56% in cases with only one patent tibial artery. The
      difference is statistically significant.

PMID- 1402222
TI  - [Individualization of operative procedures for uterine prolapse based on
      categorization using X-ray urethrocystohysterography and postoperative outcomes
      evaluated with a scoring system].
AB  - A urethrocystohysterography (UCHG) and a prolapse scoring system (PSS) have been
      used to assess the types of uterine prolapse and postoperative outcomes since
      1979. UCHG was useful in identifying the type of uterine prolapse and in
      selecting operative procedure. UCHG was done by injecting contrast medium into
      the bladder and uterine cavity and inserting a metallic bead chain into the
      urethra. A lateral pelvic X-ray was then taken at rest and during straining. The
      length of the uterus (UL), distance from the pelvic outlet (PO) to the bladder
      base (BB), distance from PO to the uterine fundus (UF), and distance from the
      ischial spine (IS) to UF were measured on the UCHG. We found that there were
      three types of uterine prolapse on the UCHG findings, type 1: cervical elongation
      without descent of uterine fundus and cystocele, type 2: uterine prolapse with
      moderate descent of uterine fundus and cystocele, and type 3: giant vaginal
      eversion including completely prolapsed uterus, marked cystocele, enterocele and
      rectocele. The operative time of vaginal hysterectomy with anterior and posterior
      colporthaphy (VH with AP repair) correlated well with UL and PO-UF distance on
      UCHG, and blood loss. Operating time was significantly shorter and amount of
      blood loss was significantly smaller in cases of Machester operation (cervical
      amputation, fixation of cardinal ligament stumps to the anterior wall of the
      remaining cervix and AP repair) than in those of VH with AP repair.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1402223
TI  - [Evolution and ecological changes of animal viruses].
AB  - Although the origin of viruses has not yet been clarified, definite differences
      in evolutionary patterns have been found among RNA. Retro and DNA viruses. These
      differences are reflected in infectious diseases. RNA viruses, which have RNA in
      their genome, replicate many times over in cells within a short period of time,
      destroying the host cells and causing an acute infection. As the error frequency
      of RNA replicase enzymes is high, the rate of evolution of RNA viruses is very
      rapid. Retroviruses also contain RNA as their genome, but the genome RNA is
      reversely transcribed to the DNA in nuclei and then incorporated into the host
      chromosome to replicate. The error frequency of reverse transcriptase is also
      high, and therefore mutations easily occur as well. The transcribed DNA is
      integrated into host DNA in the nucleus, and it remains in the integrated state
      for human entire life time, causing chronic disease or developing malignant
      tumors. As DNA viruses except poxviruses replicate inside the cell nucleus and
      the error frequency of DNA polymerase is low, the speed of mutation and the
      degree of resulting diversity are lower than those in the case of the RNA virus.
      DNA viruses tend to stay inside the body for long periods of time and easily
      become latent. In this paper, I shall discuss 1) the nature of viruses, 2) the
      origin of viruses, 3) mutation and recombination, 4) diversity of RNA viruses, 5)
      quickly changing viral diseases, 6) eradicated viral diseases, 7) chronic and
      malignant diseases, and 8) control of viral diseases.

PMID- 1402224
TI  - [Trophoblast: its functional regulation and pathophysiological profiles].
AB  - The trophoblast of the human placenta is composed of two layers:
      syncytiotrophoblast and cytotrophoblast. Cytotrophoblast displays highly
      proliferative and invasive properties, while syncytiotrophoblast displays little
      potential for proliferation. Regulatory factors involved in processes of
      proliferation and differentiation of the trophoblast still remain to be
      elucidated. Immunohistologically, myc product was predominantly localized to
      cytotrophoblastic cells. A close similarity between cytologic localization of myc
      product and tritiated thymidine labeling of placental explant suggests that myc
      protein expression is linked to trophoblast proliferation. A similar pattern of
      cytological localization was observed with the use of anti-PDGF antibody,
      supporting a possibility that PDGF also plays a role in the trophoblast
      proliferation. Human trophoblast produces two major proteins, hCG and hPL. hCG
      stimulates progesterone production by corpus luteum. hPL exerts lipolytic action
      which assures glucose supply to the fetus. In situ hybridization with cDNA probes
      for hCG(alpha, beta) and hPL revealed that mRNA expression of hCG alpha and
      probably hCG beta are initiated before syncytial formation, whereas hPL mRNA is
      expressed only in fully differentiated syncytiotrophoblast. hCG levels in
      maternal serum are the highest in early pregnancy and thereafter decline, while
      hCG alpha and hPL levels increase throughout pregnancy. In patients with
      choriocarcinoma, serum hPL levels are extremely low despite high levels of hCG.
      In this context, hCG beta mRNA levels remarkably declined in term placenta
      compared to early placenta, and hPL mRNA was little observed in choriocarcinoma.
      EGF and EGF receptor (EGF-R) in 4-5 weeks placenta were almost exclusively
      localized to cytotrophoblasts, whereas EGF and EGF-R in 6-12 weeks placenta were
      predominantly localized to syncytiotrophoblasts. In the second and third
      trimester placentas, EGF was mainly localized to cytotrophoblasts, while EGF-R
      was predominantly localized to syncytiotrophoblasts. It is of great interest that
      the cytologic localization of EGF and EGF-R in human placenta varies according to
      the age of gestation. The fact that mitotically active cytotrophoblasts in 4-5
      weeks placenta were positive for both EGF and EGF-R expression suggests that EGF
      and EGF-R may be involved in the control of multiplication of cytotrophoblasts
      very early in the first trimester. On the other hand, the fact that mitotically
      inactive syncytiotrophoblasts in 6-12 weeks placenta were positive for both EGF
      and EGF-R expression suggests that EGF and EGF-R may play a role in the induction
      of differentiated function of trophoblast in 6-12 weeks gestation. In fact, EGF
      stimulated hCG and hPL production and secretion by cultured early placental
      tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1402225
TI  - [Comprehensive study on the expression mechanism of the early pregnancy
      associated substances and the implication for embryo development--structural
      determination of early pregnancy factor molecule and analysis of its homologous
      peptides].
AB  - The human early pregnancy factor (EPF) has been solidly isolated under the
      conditions without loosing its rosette inhibition activity. The activity fraction
      has been purified as a glycoprotein with 24-30KD molecular weight. The peptide
      structure was determined in 16 amino acid sequences from N-terminal which was
      demonstrated to have a strong homology with a part of human epidermal growth
      factor precursor. This molecule has been identified from the thioredoxin
      homologous peptide originated from human placenta which has been recently
      reported as a EPF molecule by Clarke et al. The rabbit in vitro-perfusion
      experiments have been performed to elucidate the expression mechanisms of EPF
      activity. EPF has been first detected within 3 hours after fertilization in the
      local circulation of ovary and oviduct contained embryos. Although the embryo
      derived platelet activating factor (PAF) has been known as another
      preimplantation factor, the exposure of synthetic PAF induced EPF activity. Many
      other factors should implicate to express the activity and biofunction of EPF.
      The datas of EPF activity on the human in vitro fertilization and artificial
      insemination cases suggested that it demonstrated the conceptive circumstances
      and that EPF might be implicated in some regurations for the pregnancy
      establishment.

PMID- 1402226
TI  - [Role of growth factors in the regulation of embryo development and
      implantation].
AB  - Although it has been reported that growth factor and extracellular matrix (ECM)
      play an important role in the control of cell proliferation and differentiation
      in general, their involvement in the regulation of early embryogenesis and
      implantation is poorly understood. In order to clarify the mechanism underlying
      establishment and maintenance of pregnancy, the effect of EGF, TGF-alpha, TGF
      beta, TN (tenascin) on the development of preimplantation embryo and endometrial
      function were investigated. 1. Growth factors in early embryogenesis. EGF did not
      exert any significant effect on the development of mouse 2-cell embryo in vitro.
      RT-PCR revealed the presence of EGFmRNA in blastocyst and 2-cell embryo, in which
      it may be derived from maternal genome. PA-1 cells, human teratocarcinoma-derived
      cell line, share biochemical characteristics with embryo developed at and beyond
      blastocyst stage. Anti-EGF antibody but not EGF exerted inhibitory effect on DNA
      synthesis in PA-1 cell, which produced and secreted immunoreactive and bioactive
      EGF and contained high-affinity EGF receptor. These results indicate that
      autocrine/paracrine mechanism of EGF action may be a key regulation of embryo
      development at and beyond blastocyst stage. 2. Growth factors and ECM in
      implantation. The luminal fluid in DES-stimulated mouse uterus contained high
      concentrations of EGF and TGF-alpha. In vivo administration of EGF, like
      estrogen, stimulated uterine epithelial proliferation as well as progesterone
      receptor levels. In vivo administration of anti-EGF antibody or anti-TGF-alpha
      antibody significantly reduced estrogen-induced labelling index in castrated
      mouse uterus. The concomitant administration of TGF-beta 1 and TGF-beta 2 with
      estrogen further stimulated DNA synthesis in the mouse uterus than estrogen
      alone. These results suggest that growth factors partly may be a mediator of
      estrogen actions on the uterine cell proliferation and the induction of
      progesterone receptor, which are important preparative steps for implantation.
      Northern blotting and in situ hybridization using cDNA probe for mouse prepro EGF
      revealed the presence of prepro EGFmRNA in the early pregnant mouse uterus,
      especially in stroma/decidua in Day 6 of pregnancy. EGF and TGF-alpha
      significantly stimulated trophoblast outgrowth of the mouse blastocyst in vitro
      in supplementation with 0.1% of fetal bovine serum. The specific binding of EGF
      was detected in the outgrown trophoblastic cells and inner cell mass of cultured
      blastocysts by autoradiography. From these findings, it may be possible that EGF
      produced in stromal/decidual cells exerts stimulatory effect on trophoblast
      outgrowth, playing an important role in the interaction between embryo and
      endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1402227
TI  - [Implantation model in vitro].
AB  - Implantation is thought to be interactive and synchronized process between mother
      and embryo, however, the mechanisms of the early implantation process remain
      unelucidated. Therefore, the effectiveness of in vitro fertilization and embryo
      transfer is still poor. As a result; immunohistochemically, type IV collagen and
      other extracellular matrix components were detected mainly below the epithelial
      layer. Type I and III collagens were detected diffusely in the stromal layer. In
      the lower stromal layer and superficial myometrial layer, type V collagen was
      detected. Human endometrial epithelial cells performed the re-epithelialization
      following glandular formation. Rabbit endometrial cells performed also re
      epithelialization following the fold formation. The stromal cells were invaded
      into the inner layer of the folding. Estrogen added to the culture media
      stimulated the glandular formation. Progesterone administration after estrogen
      priming did not affect the glandular formation, however, the proliferation of the
      superficial epithelium and the re-epithelialized area were increased. Rabbit
      blastocysts successfully attached and implanted into the reconstructed
      endometrium. The development of the implanted embryos was morphologically normal.
      Human cultured trophoblast cells attached, invaded and penetrated into the
      extracellular matrix components. On the other hand, using type V collagen coated
      dishes, trophoblast cells could invade the stromal layer, however, type V
      collagen layer did not permit the trophoblast cells to invade into the collagen
      layer. In vivo, type V collagen, expressed in the lower stromal layer and the
      surface of the myometrium, may play a role to maintain the early embryo in the
      decidual compartment. EGTA inhibited the attachment of the blastocysts. Anti
      laminin antibody and RGDS peptide, attachment domain of laminin, also inhibited
      the implantation. These findings suggested that the Ca2+ dependent process was
      necessary for the attachment between the trophoblasts and the endometrial cells,
      and then the implantation process was triggered after the attachment to the
      laminin in basement membrane. The endometrial tissue, obtained from the infertile
      patient, was cultured on the basement membrane extract with serially obtained
      maternal serum. Addition of the maternal serum after proper administration of
      pFSH, high estrogen conditions were made in the culture dishes. These conditions
      increased the height of the glandular structure and relatively decreased the area
      of the surface epithelium. Decreased the area of surface epithelium affected the
      rate of the attachment. Endometrial cell culture system associated with
      functional and morphological characteristics was established. Serial observation
      of the endometrial cells in this system revealed the rabbit and the human
      implantation process, and the embryo-endometrial interaction.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 1402228
TI  - [Roles of calcium ion in reproductive physiology].
AB  - Physiological role and importance of calcium ion has been investigated based on
      the study of the mechanism of muscle contraction. Furthermore, calcium ion has
      been proved to have a wide variety of biological roles in hormonal secretion,
      cell proliferation and reproduction as well as in muscle contraction. In this
      lecture, I would like to show a method to measure intracellular calcium ion
      concentrations ([Ca2+]i) and to give a general information about the roles of
      calcium ion to induce various cell activities. Then I would like to talk about
      the changes in intracellular calcium concentration ([Ca2+]i) and their meaning in
      the field of reproductive physiology including uterine muscle contraction,
      pituitary LH secretion, and fertilization. 1) Uterine muscle contraction and
      calcium ion The function of calcium ion is most intensively investigated in
      muscle contraction. We show [Ca2+]i increase in cultured myometrial cells. This
      increase is inhibited by omission of extracellular calcium or addition of calcium
      channel blockers. These results support usefulness of Ca2+ channel blockers in
      treating threatened premature delivery. We also report the action of MgSO4 as an
      inhibitory agent of [Ca2+]i increase stimulated by oxytocin. 2) Pituitary
      gonadotropin secretion and calcium ion Pituitary LH secretion is regulated by
      gonadotropin releasing hormone (GnRH). GnRH induces rapid increases and then
      sustained releases of LH secretion. By the omission of extracellular calcium, or
      by addition of Ca2+ channel blockers, the sustained phase of LH secretion is
      abolished. GnRH also increase [Ca2+]i in a very similar manner to that of LH
      secretion. The [Ca2+]i increase is essential in LH secretion.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1402229
TI  - [Experimental perinatology--development of extrauterine fetal incubation system].
AB  - It goes without saying that the ideal situation for the immature fetus is growth
      within the normal environment of the maternal organism. Thus, in order to perform
      incubation that more closely resembles that of the fetus in utero, both in the
      extracorporeal and intracorporeal environment, an extrauterine fetal incubator,
      consisting of an artificial womb containing artificial amniotic fluid and a
      complete artificial placental system with a membrane oxygenator, was developed.
      Although similar experiments were performed in fetal lambs by Callaghan et al.,
      Alexander et al., and Zapol et al., the fetuses only survived incubation for
      short periods of time, no longer than 55 hours. Previously, we reported the
      relatively long-term extrauterine incubation of goat fetuses, where by the
      longest period of incubation was 236 hours. However, several major problems,
      remained to be resolved. Here we present the case in which we succeeded in
      incubating a goat fetus for 3 weeks, followed by a trial birth from an artificial
      womb.

PMID- 1402230
TI  - [The present and the future of treatment of male infertility].
AB  - About 90% of male infertile patients are complaint of semen with poor quality,
      and of which majority are caused by idiopathic disturbance of spermatogenesis. To
      date, various trials have been made to stimulate spermatogenesis by means of
      pharmaceutical administrations, their efficacies were, however, poor as expected.
      The treatment of the patients with poor quality semen is, therefore, mainly
      focused on artificial insemination, such as intrauterine insemination (IUI) and
      in vitro fertilization-embryo transfer (IVF-ET), etc. (1) To inseminate the sperm
      artificially, it is necessary to separate progressively motile sperm with normal
      morphology from seminal plasma, immotile and abnormal sperm, leucocytes and
      bacteria. There are two methods for separating progressively motile sperm, one is
      the density gradient centrifugation and another is the diffusion by their own
      motility. We have developed various types of density gradients using Percoll, a
      modified silica gel; the mono-layer Percoll method and the cushion method are
      employed for sperm concentration, and the discontinuous Percoll density gradient
      with 4 steps and the continuous-step density gradient are capable of separating
      progressively motile sperm. The continuous-step density gradient have been
      employed for 271 cases of IUI, and successful 84 pregnancies were obtained with
      the pregnancy rate of 30.9%. (2) Cryopreservation of sperm produce various
      advantages in the treatment of male infertility. Cryoaccumulation of
      oligozoospermic semen is effective for obtaining a sufficient number of sperm,
      and frequent insemination with cryopreserved sperm increase the chance of
      fertilization. To improve the quality of cryopreserved sperm, ejaculated semen
      was concentrated prior freezing by means of the continuous-step density
      gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402232
TI  - [Asthma due to allergen inhalation].

PMID- 1402231
TI  - [Uterine leiomyoma: pathogenesis and treatment].
AB  - The pathogenesis of uterine leiomyoma is controversial. Studies on the
      development of smooth muscle cells in the endoderm-derive ducts (digestive and
      urinary tracts) and in the mesoderm-derived ducts (mullerian duct) during the
      fetal period revealed that the development of smooth muscle in the mesoderm
      derived ducts (until at least 30 weeks of gestation) is slower than that of
      smooth muscle in the endoderm-derived ducts (until 12 weeks of gestation). The
      undifferentiated cells which proliferate and differentiate into smooth muscle in
      the uterus during the fetal period thus have a longer duration of unstable period
      being affected by many maternal environmental factors such as sex steroids and/or
      growth factors. The undifferentiated cells affected by some unknown maternal
      factors during the fetal period probably become the progenitor cells of
      leiomyomas. The progenitor cells of leiomyomas probably reside in the myometrium
      and begin to grow after menarche, and thrive during the years of greatest ovarian
      activity under the hormonal influence of both estrogen and progesterone, and
      following the menopause, with regression of ovarian steroids, growth of
      leiomyomas usually ceases. The growth pattern of leiomyomas indicates that LH-RH
      analogue, which induces temporal regression of ovarian steroids, becomes one of
      candidates for the conservative treatment of uterine leiomyomas. However, if we
      may treat leiomyomas with drugs, the definite diagnosis of uterine leiomyoma is
      essential. Magnetic resonance imaging (MRI) is a powerful diagnostic method for
      uterine leiomyomas. MRI gives us an information of the location and numbers of
      leiomyoma in the uterus. Moreover, it also informs us the characteristics of
      leiomyomas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402233
TI  - [Etiology of asthma: viewpoint from genetic aspect].

PMID- 1402234
TI  - [Essential tests for diagnosis of bronchial asthma].

PMID- 1402235
TI  - [Physiopathology and diagnosis of asthma].

PMID- 1402236
TI  - [Physiopathology and diagnosis of allergic bronchopulmonary aspergillosis].

PMID- 1402237
TI  - [General concept of cough variant asthma].

PMID- 1402238
TI  - [Treatment of status asthmaticus].

PMID- 1402239
TI  - [Application of adrenal cortex hormones in the treatment of asthma].

PMID- 1402240
TI  - [Life guidance for patients with asthma].

PMID- 1402241
TI  - [Bronchial hyperreactivity in patients with asthma].

PMID- 1402242
TI  - [Role of eosinophils in asthma].

PMID- 1402243
TI  - [Role of chemical mediators and cytokines in the lung].

PMID- 1402244
TI  - [A case of thrombotic thrombocytopenic purpura with prominent whole body edema
      and choroidal detachment].

PMID- 1402245
TI  - [A case of common bile duct neoplasm with carcinosarcoma of the gallbladder].

PMID- 1402246
TI  - [A case of leptospirosis manifesting acute pancreatitis and cholecystitis].

PMID- 1402247
TI  - [A case of von Recklinghausen's disease followed by intra-hepatic neurofibroma].

PMID- 1402248
TI  - [Tissue-plasminogen activator and new thrombolytic enzyme].

PMID- 1402249
TI  - [Diagnostic significance of leukemia cell markers].

PMID- 1402250
TI  - [Significance of oncogenes in diagnosis of leukemia].

PMID- 1402251
TI  - [Therapy of various diseases complicated with leukemia].

PMID- 1402252
TI  - [Mechanism of action of anti-leukemia agents and adverse effects].

PMID- 1402253
TI  - [Treatment of acute lymphocytic leukemia].

PMID- 1402254
TI  - [Secondary leukemia and the countermeasures].

PMID- 1402255
TI  - [A case of sinus-bronchi syndrome repeatedly detected Bordetella bronchiseptica
      from sputum].

PMID- 1402256
TI  - [A case of dilated cardiomyopathy with intractable heart failure treated with
      adjunctive therapy of pimobendan and denopamine].

PMID- 1402257
TI  - [A case of ankylosing spondylitis manifesting left ventricular wall thickening
      mimicking dilated cardiomyopathy].

PMID- 1402259
TI  - [Anti-centromere antibody positive case of malignant lymphoma].

PMID- 1402258
TI  - [A case of organophosphate poisoning complicated with cardiomyopathy].

PMID- 1402260
TI  - [Future of medicine in 21st century].

PMID- 1402261
TI  - [Diagnostic and therapeutic significance of chromosome changes in leukemia].

PMID- 1402262
TI  - Hand surgery: the skin and its contents.

PMID- 1402263
TI  - Thumb reconstruction: a review and philosophy of management.

PMID- 1402264
TI  - Surgery for cerebral palsy: Part 1. Classification and operative procedures for
      pronation deformity.
AB  - 32 patients with cerebral palsy underwent operations for pronation deformity. The
      deformity is classified into four groups. Patients in group 1 are capable of
      supination beyond neutral. No surgery is necessary. Those in group 2 are able to
      supinate to the neutral position. A pronator quadratus release is advised and may
      be combined with a flexor aponeurotic release. In group 3, patients have no
      active supination. However a full range of passive supination is readily
      achieved. A pronator teres transfer is advised. Patients in group 4 have no
      active supination. Full passive supination may be present, but is tight. A flexor
      aponeurotic release and a pronator quadratus release may unmask active supinator
      activity. An active transfer for supination is possible as a secondary procedure.

PMID- 1402265
TI  - Surgery for cerebral palsy: Part 2. Flexion deformity of the wrist and fingers.
AB  - 34 children with cerebral palsy had operations to correct flexion deformities of
      the wrist and fingers. 30 out of 34 patients were improved functionally and
      cosmetically. Zancolli's classification provides sound guidelines on which to
      base surgical decisions.

PMID- 1402266
TI  - Madelung deformity: surgical prophylaxis (physiolysis) during the late growth
      period by resection of the dyschondrosteosis lesion.
AB  - The majority of cases of Madelung deformity are caused by hereditary
      dyschondrosteosis at the wrist. The principal lesion in the ulnar zone of the
      distal radial physis retards growth asymmetrically, especially in late childhood.
      Resection of this zone and its replacement with autologous fat (Langenskiold
      procedure, or physiolysis) restores growth and minimizes deformity. The resection
      of an abnormal ligament tethering the lunate proximally may assist carpal
      advancement. A series of 17 patients (24 wrists) treated over a 12-year period is
      presented, with sufficient follow-up for evaluation of 11 patients (15 wrists).
      The results of this prophylactic procedure are encouraging, and, if it is
      performed early, the authors believe that Madelung deformity may be preventable,
      or at least controllable.

PMID- 1402267
TI  - A review of distal ulnar hemi-resection arthroplasty.
AB  - 15 patients with pain and disability on the ulnar side of the wrist were treated
      by distal ulnar hemiresection arthroplasty. The patients' diagnoses fell into
      three groups, namely ulnocarpal impingement, primary osteoarthritis of the distal
      radio-ulnar joint and traumatic disruption of the distal radioulnar joint.
      Patients were assessed pre- and post-operatively on the basis of pain and forearm
      rotation. Grip strength was assessed and compared with the unaffected side. Their
      subjective view of the operation was also sought. The best results were seen in
      those patients with osteoarthritis or traumatic disruption, although all patients
      were improved and none made worse. No patient complained of weakness although
      three were assessed to have a weak grip. Subjectively, 14 of the 15 were pleased
      or very pleased. The procedure was well tolerated and had low morbidity.

PMID- 1402268
TI  - The Sauve-Kapandji operation. Technique and results.
AB  - For distal radio-ulnar joint disorders, the Sauve-Kapandji procedure, previously
      attributed to Lauenstein, of arthrodesis of the joint and distal ulnar
      pseudarthrosis is a very useful procedure, yet is not often practised. This paper
      describes the technique and presents the results of 81 procedures in 71 patients.
      There was excellent patient satisfaction. The procedure is a reliable and
      effective method of dealing with distal radio-ulnar joint disorders, especially
      in rheumatoid arthritis and following distal radial fractures. Some changes to
      previous techniques are emphasized.

PMID- 1402269
TI  - The Herbert bone screw: a ten year perspective.
AB  - It is now over ten years since the Herbert bone screw was first released in
      Australia. In 1984, Herbert and Fisher first published their experience with the
      use of this new bone screw in the management of scaphoid fractures. Since that
      time, there has been a growing interest in the technique and over 60 articles
      have appeared in the English literature. The purpose of this paper is to review
      and comment on the relevant publications as they relate to the biomechanical
      properties of the screw, to its use in the management of scaphoid fractures and
      to other applications in surgery of the hand.

PMID- 1402270
TI  - Fracture of the proximal phalanx. An unusual complication of pulley
      reconstruction in a child.
AB  - We report a case of a fracture occurring in the proximal phalanx of a child
      following pulley reconstruction. The operative technique and the difficulties of
      pulley reconstruction in the immature skeleton are discussed.

PMID- 1402271
TI  - Volar plate arthroplasty for closed proximal interphalangeal joint injuries.
AB  - The anatomy and histology of the volar plate at the proximal interphalangeal
      joint and the mechanism of fracture/subluxation of the base of the middle phalanx
      in closed proximal interphalangeal joint injuries is reviewed. Our current
      technique of repair for these injuries and its evolution from Eaton's original
      procedure is described. The results of 71 cases of volar plate arthroplasty
      performed over a five-year period for fracture/subluxations of the proximal
      interphalangeal joints are presented with follow-up ranging from six months to
      four years. 62 (87%) patients achieved a stable pain-free joint with a range of
      motion from 5 degrees to 95 degrees within two months. Complications were
      uncommon and correctable with an overall eventual patient satisfaction rate of
      94%.

PMID- 1402272
TI  - Intraosseous ganglion cyst of the lunate: diagnosis and management.
AB  - Intraosseous ganglion cyst of the lunate is an uncommon lesion and cause of wrist
      pain. Histopathologically it is identical to the common dorsal wrist ganglion and
      treatment by arthrotomy, curettage of the ganglion and bone graft resulted in
      clinical improvement in nine patients, six of whom became symptom-free.

PMID- 1402273
TI  - Non-subungual melanomas of the hand.
AB  - The non-subungual area of the hand is a rare anatomical site for malignant
      melanoma, lesions in this site comprising only 0.37% of 8,584 cutaneous melanomas
      in the Sydney Melanoma Unit database. This is approximately the same frequency of
      melanoma as is found on the subungual region of the hand, which represents a much
      smaller surface area. Not only is the sub-site distribution on the hand unusual
      but in addition the histogenetic types of melanoma found on the dorsum of the
      hand are not those commonly encountered on sun exposed skin. In this study,
      comparison is made between melanomas occurring on the non-subungual areas of the
      hand and those on the foot, an anatomically similar surface area. Comparison is
      also made between melanomas arising on the dorsal non-subungual surface of the
      hand and those on the face, a region with an equivalent surface area and similar
      sun exposure. The results of surgical treatment of 31 melanomas of the non
      subungual region of the hand are reviewed.

PMID- 1402274
TI  - Complex physical therapy for the lymphoedematous arm.
AB  - Complex physical therapy was used in 78 patients with post-mastectomy lymphoedema
      (17 with grade 1 and 61 with grade 2). This involves: skin hygiene, a special
      lymphatic massage, compression bandaging and garments, and special exercises
      which supplement the massage. Two courses of treatment were given, lasting four
      weeks each, with a year between them. There was a highly significant decrease in
      the oedema in both grades, with more than 50% removed in the first course of
      treatment and 50% of the remainder in the second. There was even a small, but
      very significant decrease during the interval between the two courses.

PMID- 1402275
TI  - Iatrogenic injection injuries of the hand and upper limb.
AB  - 30 cases of iatrogenic injection injuries to the hand and upper limb are
      reported. 16 followed therapeutic injections (steroids--11 cases, infusions--five
      cases) and 14 occurred during anaesthetics procedures (local blocks--ten cases,
      general anaesthetics--four cases). Guidelines for minimizing the risk of
      injection injury are outlined.

PMID- 1402276
TI  - Radical microarteriolysis in the treatment of vasospastic disorders of the hand,
      especially scleroderma.
AB  - Arterial spasm due to exaggerated sympathetic response is an important mechanism
      for Raynaud's phenomenon in scleroderma associated often with periadventitial
      scarring. The results of cervical sympathectomy have been unsatisfactory in the
      upper limb because of additional sympathetic pathways. Flatt therefore devised a
      distal sympathectomy by stripping the vessels of their adventitia over a short
      length of artery. The results of this operation were found by Wilgis in a large
      series to be poor in patients with scleroderma. A radical distal
      microarteriolysis including adventitia and surrounding scar is described and the
      results in 13 patients, 11 with scleroderma, are reported. Minimum follow-up is
      one year. All patients had relief from pain at rest and healing of painful
      ulceration. Mild recurrence of small ulcers was seen in only four patients.

PMID- 1402277
TI  - Regression of Dupuytren's contracture.
AB  - The phenomenon of clinical regression of Dupuytren's contracture is described and
      discussed. It is already recognized and used in fasciotomy where it follows the
      release of longitudinal tension. The quite extraordinary resolution produced by
      continuous passive skeletal traction in extension is presented. Regression
      beneath grafted skin is described and discussed with its clinical implications.
      The generally accepted view of Dupuytren's contracture being "irreversible" now
      presents a challenge for further clinical and pharmacological studies. The
      possibility of non-surgical control does exist.

PMID- 1402278
TI  - Silastic replacement of the trapezium.
AB  - A retrospective study has been made of the long-term results of silastic
      replacement of the trapezium, including functional, clinical and radiological
      assessment of 43 hands, one to 13 years postoperatively. The results showed good
      function and relief of pain in 88% of hands. Radiolucent bone lesions, presumably
      due to silastic particle reaction, occurred in 53% of hands, but their presence
      did not correlate well with symptoms. Four patients (9%) developed significant
      synovitis which was improved by removal of the prosthesis. In this series,
      clinical silastic synovitis occurred in the first four years, and its incidence
      did not increase with further follow-up to 13 years.

PMID- 1402279
TI  - Intercarpal arthrodesis by dowel bone grafting.
AB  - Successful intercarpal arthrodesis requires a stable fusion with maintenance of
      correct alignment and spatial relationship of the carpus. The technique described
      utilizes a series of tube saws to fashion the arthrodesis bed and then insert a
      sized iliac crest dowel bone graft with a tight interference fit. This technique
      has been used in 24 patients over a two-year period in both medial and lateral
      column intercarpal fusions. All wrists had fused by the tenth post-operative
      month. The technique is precise, reproducible and technically simple with a high
      fusion rate and minimal donor site morbidity.

PMID- 1402280
TI  - The plantaris tendon as a tendo-osseous graft. Part I. An anatomical study.
AB  - Comparative studies have shown that bone-bone union develops faster than a
      junction between grafted tendon and bone, and would thus allow earlier post
      operative movement, limiting adhesion formation. In this context the nature of
      the insertion of the plantaris tendon into the calcaneus is reviewed as a
      possible source of composite bone-tendon grafts. It is proposed that the
      composite plantaris tendon with its bony block attachment is inserted through a
      hole in the distal phalanx of the finger creating an immediate firm distal
      fixation. From cadaver dissections it was found that in at least 80% of cases the
      insertion of the plantaris tendon was directly into the calcaneus, independent of
      the tendo Achilles, and was therefore suitable for use as the proposed tendon
      graft.

PMID- 1402281
TI  - The plantaris tendon as a tendo-osseous graft. Part II. Clinical studies.
AB  - To minimize adhesions following tendon repair, early post-operative movement is
      recommended. This has proved difficult with tendon grafting because of weakness
      of the repair sites, particularly distally, and because of slow
      revascularization. A potential solution is the use of a composite tendon-bone
      graft in which a bone block is attached to the end of the tendon. The tendon is
      threaded through a hole in the distal phalanx from the dorsal to the palmar side
      and impacted like a cork to create an immediate strong fixation. The tendon
      itself is then tunnelled through the pulley system and the proximal repair is
      carried out with a multiple weave technique which can withstand immediate active
      movement. The ideal tendon-bone complex is the plantaris attached to a segment of
      calcaneus. A preliminary report with two case studies is presented.

PMID- 1402282
TI  - Abductor pollicis longus: a case of mistaken identity.
AB  - Abductor pollicis longus, long regarded as a motor for the thumb, is anatomically
      and functionally a radial deviator of the wrist and should be so named. The
      abductor carpi is proposed. If the other radial deviators of the wrist are acting
      this tendon can be selectively utilized as a transfer without loss of function.
      Reflex spasm of this muscle probably plays an important role in the radial
      deviation deformity seen in the rheumatoid hand.

PMID- 1402284
TI  - Finkelstein's test: a descriptive error that can produce a false positive.
AB  - Over the last three decades an error in performing Finkelstein's test has crept
      into the English literature in both text books and journals. This error can
      produce a false-positive, and if relied upon, a wrong diagnosis can be made,
      leading to inappropriate surgery.

PMID- 1402285
TI  - Andrew Russell Murray and the Hand Clinic at Leith Hospital 1942-1946.

PMID- 1402283
TI  - Closed rupture of both flexor tendons in the same digit.
AB  - Closed ruptures of both normal flexor tendons in the same finger are extremely
      rare, only nine cases having been reported in the literature. We describe the
      case of a patient who sustained a closed rupture of both flexor digitorum
      profundus and flexor digitorum superficialis of the ring finger, following a
      forced hyperextension injury. The patient was treated by a two stage
      reconstruction of the flexor digitorum profundus. He regained full flexion and
      extension of the finger.

PMID- 1402286
TI  - A history of the Australian Hand Club.

PMID- 1402287
TI  - Some early history of hand surgery in Australia.

PMID- 1402288
TI  - Subcutaneous release of trigger thumb and fingers in 210 fingers.

PMID- 1402289
TI  - Does training reduce the incidence of industrial hand injuries?

PMID- 1402290
TI  - Detecting fractures of the scaphoid: the value of comparative X-rays of the
      uninjured wrist.

PMID- 1402292
TI  - Ocular hypotensive actions of serotonin antagonist-ketanserin analogs.
AB  - A series of ketanserin analogs were studied for their effects on intraocular
      pressure (IOP) recovery curve of rabbits infused with hypertonic saline. Eight
      out of 31 compounds tested showed a marked delay in IOP recovery indicating that
      they are potential antiglaucoma agents. Five out of eight compounds showed equal
      suppression of the IOP recovery curves of treated and contralateral eyes
      indicating that these compounds could be absorbed systemically to affect the IOP
      of the contralateral eye. There were three compounds (GC 679, GC 646, and GC 526)
      which showed more suppression of the IOP recovery curve of the treated eye than
      that of the contralateral eye, indicating that these drugs might act primarily at
      the local site to lower the IOP. Therefore, these three compounds could produce
      antiglaucoma actions with little systemic side effects, if any.

PMID- 1402291
TI  - Six week safety study of 2% MK-927 administered twice daily to ocular
      hypertensive volunteers.
AB  - Ocular hypertensive patients were enrolled in a 6-week double-masked safety study
      of 2% MK-927 (27 patients), a topically active carbonic anhydrase inhibitor,
      administered bilaterally b.i.d.; 9 additional patients received 0.5% timolol as
      the control agent. Intraocular pressure (IOP) was measured weekly prior to a.m.
      drug administration; twelve hour diurnal curves were performed prestudy and at 3
      and 6 weeks. The mean reduction of IOP prior to a.m. drug administration ranged
      from 1.2 +/- 4.4 mm Hg (SD) to 3.0 +/- 4.2 mm Hg with MK-927 and from 4.7 +/- 3.9
      mm Hg to 8.8 +/- 0.6 mm Hg with timolol. Mean outflow facility measured
      tonographically prestudy and on days 33 to 42 four hours after a.m. drug
      administration was unchanged in both groups. Corneal sensitivity (Cochet-Bonnet),
      corneal thickness (ultrasound pachymetry), Schirmer tear testing, and extensive
      ophthalmologic and medical examinations, and hematologic studies were not
      substantially altered throughout the study. In this longest chronic
      administration study to date, MK-927 did not cause adverse ocular or systemic
      side effects.

PMID- 1402293
TI  - Quantitative determination of the melanin contents in ocular tissues from human
      blue and brown eyes.
AB  - This paper deals with our findings on the quantities of melanin in the tissues
      from blue and brown eyes. The amount of melanin in the iris, ciliary body and
      retinal pigment epithelium-choroid was separately determined. The results are
      expressed as the amount of melanin in mg tissue as well as the amount of melanin
      in the whole tissue. The results showed that there was no statistically
      significant difference between the melanin content of the iris in blue and brown
      eyes. However the ciliary body and retinal pigment epithelium-choroid from brown
      eyes had more melanin than the corresponding tissues from blue eyes. Blue and
      brown eyes with higher colour intensity had more melanin than the corresponding
      eyes with lesser intensity of colour. It is suggested that the differences
      between brown and blue eyes in their melanin content may have relevance to the
      pharmacokinetics of drugs that bind to melanin. This would mean that the larger
      amounts of melanin would decrease the initial levels of the drugs and would
      increase the drug levels after prolonged periods.

PMID- 1402294
TI  - The efficacy of aldose reductase inhibitors on polyol accumulation in human lens
      and retinal pigment epithelium in tissue culture.
AB  - The formation of excess sugar alcohol mediated by aldose reductase (AR) and its
      intracellular accumulation in lens with resultant hydration is thought to be the
      initiating mechanism in the pathogenesis of diabetic and galactosemic cataracts.
      AR is also involved in other diabetic complications including retinopathy and
      neuropathy. Therefore, there is heightened interest in developing effective AR
      inhibitors (ARIs) for possible clinical use in human diabetes. However, the
      evaluation of these drugs for potential clinical use requires that the compounds
      be evaluated in appropriate target tissues since AR from different tissues is
      known to exhibit differential susceptibility to ARIs. The relative efficacy of
      ARIs in human lens epithelium (HLE) and human retinal pigment epithelium (HRPE)
      was studied by measuring the degree of inhibition of galactitol formation at
      various concentrations of ARI following incubation of cells in high galactose
      media for 72 hrs. Regardless of the structural characteristics of the ARIs
      investigated, higher doses were required to inhibit polyol synthesis in HRPE as
      compared to HLE cells. Based on ED50 values, dose required for 50% inhibition,
      the order of potencies against both HLE and HRPE enzymes was AL-4114 greater than
      AL-3152 greater than AL-1576 greater than tolrestat greater than statil greater
      than sorbinil. Since some ARIs are known to be bound to plasma proteins, it is
      conceivable that the observed differences in ED50 values could be due to
      differential binding to serum proteins in the culture medium. This possibility
      was examined by employing cultures of dog lens epithelium (DLE). These cells,
      which synthesize much higher levels of galactitol than HLE and HRPE, could be
      maintained in serum-free media for short periods (4 hrs) of time. The results,
      which demonstrate that the extent of polyol inhibition was the same in the
      presence or absence of serum, suggest that the differences in the potency of the
      inhibitors may reflect their inherent activity against AR in HLE and HRPE cells.

PMID- 1402295
TI  - The effect of some macromolecular ionic complexes on the pharmacokinetics and 
      dynamics of ocular cyclopentolate in rabbits.
AB  - The effect of mucoadhesive polymeric vehicles on the mydriatic efficacy, and on
      the systemic and ocular absorption of cyclopentolate from eyedrops was studied in
      albino rabbits. Combining cyclopentolate base to polygalacturonic (CY-PGA) or
      hyaluronic (CY-HA) acid resulted in an increased mydriatic effect when compared
      with cyclopentolate hydrochloride (CY-HCl). During the first half an hour, the
      systemic absorption of cyclopentolate was lower after CY-PGA than after CY-HCl.
      The ocular penetration of cyclopentolate, based on drug concentrations in aqueous
      humor 30 minutes after the eyedrop instillation, was increased 3 fold when the
      polygalacturonate complex was used. CY-PGA, as well as other polymeric salts,
      might offer a possibility to increase the therapeutic index of cyclopentolate.

PMID- 1402297
TI  - FGF promotes corneal stromal fibroblast motility.
AB  - It is well-known that growth factors accelerate wound healing by stimulating
      mitosis. Growth factors may also directly stimulate the motility of individual
      cells. We employed two different experimental methods to determine if fibroblast
      growth factor (FGF) enhances the individual motility of corneal stromal
      fibroblasts (independent of mitogenic effects). The effects of FGF on the
      motility of tissue-cultured rabbit corneal stromal fibroblasts were investigated
      in a modified Boyden chamber and by the agarose drop motility assay. Both assays
      showed a significant enhancement of stromal fibroblast motility by FGF at 100
      ng/ml. It appears, therefore, that FGF may promote corneal stromal wound healing
      not only by increased cellular proliferation, but also by increased cellular
      motility.

PMID- 1402296
TI  - Leukotrienes and sensory innervation in blood-aqueous barrier disruption in the
      dog.
AB  - The effect of a specific 5-lipoxygenase inhibitor, PF5901 (5% in corn oil), on
      disruption of the blood-aqueous barrier (BAB) in the dog was investigated using a
      unilateral mild paracentesis model. BAB breakdown was quantitated using anterior
      chamber fluorophotometry. Fluorescence in the eyes of the PF5901 group was not
      statistically significantly different (P greater than 0.05) from that in the
      vehicle group. A tendency towards greater fluorescein concentrations was noted in
      the PF5901 treated eyes. It was concluded that leukotrienes are not important
      mediators of BAB disruption in this model and that leukotriene inhibitors may
      actually exacerbate disruption due to shunting of arachidonate metabolism towards
      the cyclooxygenase and/or epoxygenase pathways. In a second experiment, the
      effects of proparacaine and flurbiprofen were evaluated on blood-aqueous barrier
      disruption and pupil size following a more severe paracentesis. Flurbiprofen
      dampened both barrier disruption and the miotic response but proparacaine
      suppressed neither reaction, suggesting that, in the dog, prostaglandins are more
      important mediators of the ocular irritative response than are sensory
      neuropeptides.

PMID- 1402298
TI  - The effects of transferrin receptor antibody, transferrin receptor antibody bound
      to Pseudomonas exotoxin and transforming growth factor-alpha bound to Pseudomonas
      exotoxin on human tenon's capsule fibroblast proliferation.
AB  - Pharmacological agents which modulate the wound healing process by the inhibition
      of proliferation of fibroblasts may improve the success of glaucoma filtration
      surgery. Since cell proliferation is essential to the wound healing process, we
      targeted the surface receptors that are associated with proliferating cells. We
      present the effects of three such agents-purified mouse anti-human transferrin
      receptor monoclonal antibody 42/6 (anti-TfR-42/6), anti-transferrin monoclonal
      antibody bound to a Pseudomonas exotoxin (anti-TfR-PE40) and transforming growth
      factor-alpha Pseudomonas exotoxin (TGF-alpha-PE40)--on human fibroblasts from
      Tenon's capsule. The inhibition of human subconjunctival fibroblast proliferation
      by anti-TfR-42/6 (with a concentration up to 25 micrograms/ml) and by anti-TfR
      PE40 and TGF-alpha-PE40 (both with a concentration range of 5000-0.00001
      micrograms/ml) was determined by colorimetric (OD), and cell counting (CC) assays
      over a 9-day period. Neither anti-TfR-42/6 nor anti-TfR-PE40 had an
      antiproliferative effect on the fibroblasts. TGF-alpha-PE40 demonstrated an
      antiproliferative effect in a dose response manner. The mean 50% inhibitory dose
      (ID50) by OD was 32.91 micrograms/ml, while the ID50 by CC was 27.88
      micrograms/ml. EGF was used as a negative control for TGF-alpha-PE40 toxin. The
      inhibitory effect of the toxin conjugate was completely blocked by the addition
      of 1000 micrograms/ml of EGF. These in vitro studies show that TGF-alpha-PE40 may
      be useful in modulating the proliferation of human ocular fibroblasts; they also
      give some indication of drug dosages for future in vivo testing.

PMID- 1402299
TI  - Knowledge-based decision support for patient monitoring in cardioanesthesia.
AB  - An approach to generating 'intelligent alarms' is presented that aggregates many
      information items, i.e. measured vital signs, recent medications, etc., into
      state variables that more directly reflect the patient's physiological state.
      Based on these state variables the described decision support system AES-2 also
      provides therapy recommendations. The assessment of the state variables and the
      generation of therapeutic advice follow a knowledge-based approach. Aspects of
      uncertainty, e.g. a gradual transition between 'normal' and 'below normal', are
      considered applying a fuzzy set approach. Special emphasis is laid on the
      ergonomic design of the user interface, which is based on color graphics and
      finger touch input on the screen. Certain simulation techniques considerably
      support the design process of AES-2 as is demonstrated with a typical example
      from cardioanesthesia.

PMID- 1402300
TI  - A parallel implementation of a multi-state Kalman filtering algorithm to detect
      ECG arrhythmias.
AB  - Detecting arrhythmias from the electrocardiogram (ECG) is of great importance for
      the continued development of intelligent cardiovascular monitors (ICM). An ICM's
      main goal is to present to the clinician a 'high-level' analysis of the patient's
      condition (e.g., the patient is slightly hypovolemic) based upon 'low-level'
      physiologic signals (e.g., blood pressure, heart rate, etc.). This paper reports
      on a parallel implementation of a multi-state Kalman filtering algorithm, within
      a prototype ICM, to help detect ECG arrhythmias. Preliminary test results show
      that the parallel, multi-state implementation performed exactly as the original
      sequential version. Several different rhythm disturbances were correctly
      identified after 3-5 beats. We conclude that our parallel implementation of the
      multi-state Kalman filter provides a faster and still reliable means of
      accurately detecting ECG arrhythmias in real-time.

PMID- 1402301
TI  - CASSPERT--an expert system to guide choice and strategy in coronary angioplasty.
AB  - Coronary angioplasty is a technique widely used in the treatment of coronary
      artery disease. The success of coronary angioplasty depends on patient selection,
      the use of an appropriate technique, and to a large extent a carefully considered
      choice of angioplasty equipment. The authors have developed an expert system
      which can assist in this decision making process. CASSPERT was developed using
      the expert system shell 'Leonardo' running on a standard Personal Computer. The
      user interacts with CASSPERT to build up a detailed profile of clinical,
      investigational and angiographic features of the patient. This information,
      together with technical data stored within Leonardo's own object orientated
      database, is used to infer a suitable choice of equipment. To make the expert
      system useful in clinical practise, it was interfaced within a functional,
      readily accessible, data acquisition and storage environment which could be used
      within the day to day running of the department.

PMID- 1402302
TI  - Proposal of a computerized algorithm for continuous wave CO2 laser on-line
      control during orthopaedic surgery. Phase I: theoretical introduction and first
      in vitro trials.
AB  - New data obtained from treating polymethylmethacrylate (PMMA) with a non-moving
      cw- 10 watt-CO2 laser-beam focused at 2.5'', 5'', 7.5'' and 15.75'' are
      presented. . The final equations R(tc) and Z(tc) for each focal length are
      proposed. A very interesting correlation between the focal lengths in use and the
      integrated values of R and Z between 0 and 2 sec has been identified and
      discussed. This result has been used as basis to define a convenient operative
      protocol to follow during the planning phase of critical osteotomies or bone
      cement removal operations using a continuous-wave CO2 laser-beam set to any
      output power and focused by a set of most common, moving or non-moving focal
      lengths placed on the operating area. With a simple equation, it is possible to
      compare craters obtained with moving and non-moving laser-beams at different
      operative conditions between 0 and 2 sec, time interval which covers the majority
      of cases. A value of 2.3 +/- 0.1 between ablated volumes of PMMA and bone tissue
      has been identified. Several case studies regarding orthopaedic procedures from
      Literature are here reported and compared to the present LCA model. The
      computerized on-line flow of information for the laser-beam optimization and
      safety control is also described. Finally, a method for the simultaneous data
      collection from several operating rooms via a Local Area Network (LAN-Industry
      Standard IEEE) onto a central data base for later consultation is proposed in its
      general design.

PMID- 1402303
TI  - Clinical evaluation--continuous real-time intra-arterial blood gas monitoring
      during anesthesia and surgery by fiber optic sensor.
AB  - A clinical evaluation of the clinical utility, techniques of use, durability,
      accuracy, and potential complications of a newly available system for the
      continuous real-time, intra-arterial monitoring of arterial blood gas and acid
      base status (ABG) has been studied (Optex BioSentry System, Optex Biomedical,
      Incorporated, The Woodlands, Texas, U.S.A.). The system consists of three
      separate fiber optic channels with contained fluorescent and absorbant chemical
      analytes imbedded in a single probe and capable of insertion inside of a twenty
      gauge indwelling arterial catheter (The Optex Optode Sensor), along with an
      external monitor. The system was utilized during anesthesia and surgery in the
      care of five informed patients. Constant trend monitoring of all three variables
      was deemed satisfactory in four of the patients. The fifth sensor was damaged by
      a surgical assistant while in place and ceased to function. Comparison of Optode
      sensor readings with standard clinical laboratory ABG analysis was excellent in
      three uncomplicated patients (pH: bias -0.0183 pH units, precision: 0.0237 pH
      units; PCO2: bias 3.22 mmHg, precision 2.04 mmHg; PO2: bias -5.94 mmHg, precision
      11.74 mmHg). Postoperative study suggested that discrepancies in a fourth patient
      may have been due to an incorrect 'offset' applied to the Optode sensor yielding
      a constant error.

PMID- 1402304
TI  - INFORM: European survey of computers in intensive care units.
AB  - The aims of this study were (a) to survey and evaluate the impact of information
      technology applications in High Dependency Environments (HDEs) on organizational,
      psychological and cost-effectiveness factors, (b) to contribute information and
      design requirements to the other workpackages in the INFORM Project, and (c) to
      develop useful evaluation methodologies. The evaluation methodologies used were:
      questionnaires, case studies, objective findings (keystroke) and literature
      search and review. Six questionnaires were devised covering organizational
      impact, cost-benefit impact and perceived advantages and disadvantages of
      computerized systems in HDE (psychological impact). The general conclusion was
      that while existing systems have been generally well received, they are not yet
      designed in such a developed and integrated way as to yield their full potential.
      Greater user involvement in design and implementation and more emphasis on
      training emerged as strong requirements. Lack of reliability leading to parallel
      charting was a major problem with the existing systems. It proved difficult to
      assess cost effectiveness due to a lack of detailed accounting costs; however, it
      appeared that in the short term, computerisation in HDEs tended to increase
      costs. It is felt that through a better stock control and better decision making,
      costs may be reduced in the longer run and effectiveness increased; more detailed
      longitudinal studies appear to be needed on this subject.

PMID- 1402305
TI  - Ultra slow wave pressure variations in the anal canal before and after lateral
      internal sphincterotomy.
AB  - Ultra slow waves (USW's) in the anal canal are discrete pressure fluctuations
      with a low frequency (1-2/minute) and high amplitude (> or = 10% above or below
      baseline resting pressure). To investigate the nature of these USW's, anorectal
      manometry was performed in 20 control subjects as well as in 58 patients
      presenting with anal fissure or symptomatic hemorrhoids, before and 2 weeks after
      lateral internal sphincterotomy. USW's could be demonstrated in two control
      subjects and in 29 patients. The median value of maximum anal resting pressure
      (MARP) in the two control subjects with USW's was significantly higher than the
      median MARP in the 18 control subjects without USW's (181.5 vs. 92 cm H2O, p <
      0.001, two-tailed Mann-Whitney test). The same difference was found between MARP
      in patients with and without USW's (158 vs. 138 cm H2O, p < 0.05, two-tailed Mann
      Whitney test). All patients were treated by means of lateral internal
      sphincterotomy (LIS). Two weeks after this procedure USW's had disappeared in
      half of the patients. The MARP in these patients was reduced to a level found in
      control subjects without USW's. This pressure reduction was significantly greater
      than in patients with persistent USW's (40% vs. 15%, p < 0.02, two-tailed Mann
      Whitney test). Because USW's are associated with high MARP and disappear when
      such a high anal canal resting pressure is reduced by LIS to a level found in
      control subjects without USW's, it can be concluded that USW's are the
      manifestation of increased activity of the internal anal sphincter.

PMID- 1402306
TI  - The failing pelvic pouch conversion to continent ileostomy.
AB  - Excision of a failing pelvic pouch is often a great disappointment for the
      patient. It is also an unfortunate decision considering that a significant length
      of terminal ileum is sacrificed. Transformation of the pouch to a continent
      ileostomy is an alternative. Five patients with a malfunctioning pelvic pouch
      have had their pouch converted to a continent ileostomy. The operative technique
      is described.

PMID- 1402307
TI  - Induction chemotherapy with carboplatin and 5-fluorouracil in combination with
      radiotherapy in loco-regionally advanced epidermoid carcinoma of the anus-
      preliminary results.
AB  - During the last decade conservative treatment of anal carcinoma based on
      radiotherapy has gained popularity. Radiotherapy is often combined with
      concurrent chemotherapy although no firm evidence exists that such combinations
      are more effective than radiotherapy alone. Treatment results with respect to
      anal sphincter function are generally better for small tumors. In an effort to
      improve the treatment results for locally advanced epidermoid anal carcinoma, a
      selection of patients with such tumors has been treated with induction
      chemotherapy comprising two or three courses of a combination of carboplatin 300
      350 mg/m2 i.v. and 5-fluorouracil 1,000 mg/(m2 x d) x 5 d prior to radiotherapy.
      Six female patients aged 37 to 74 have completed the regimen. All had complete
      tumor regressions at conclusion of radiotherapy. No recurrence has yet occurred
      but the follow-up period is still short (8-21 months). No interruption of
      chemotherapy due to toxic side effects was necessary and no severe toxicity
      registered. Further study is needed to evaluate the efficacy and toxicity of the
      regimen, but these early findings are promising.

PMID- 1402308
TI  - The stapled functional end-to-end anastomosis following colonic resection.
AB  - To determine the results of our experience with the use of staples for
      construction of anastomoses following colonic resection, a series of 223
      anastomoses performed in 205 patients was reviewed. Indications for operation
      included malignancy, benign neoplasms, inflammatory bowel disease, and several
      miscellaneous entities. A functional end-to-end anastomosis using the standard
      GIA cartridge and the TA 55 instruments was performed. The operative mortality
      was 1.5% with none of the deaths related to the anastomosis. Intraoperative
      complications encountered included bleeding (21), leak (1), tissue fracture (1),
      instrument failure (4), and technical error (3). Early postoperative
      complications related or potentially related to the anastomosis included bleeding
      (5), pelvic abscess (1), fistula (1), peritonitis (2), ischemia of anastomosis
      (1). Late complications included five patients with small bowel obstruction, two
      of whom required operation. Anastomotic recurrences developed in 5.9% of
      patients. Our experience gained with stapling instruments has shown them to be a
      reliable method for performing anastomoses in the colon in a safe and expeditious
      manner.

PMID- 1402309
TI  - Successful local repair of paracolostomy hernia with a newly developed prosthetic
      device.
AB  - The basic cause of paracolostomy hernia is enlargement of the trephine opening in
      the abdominal wall, due to tangential forces working on the circumference of the
      opening. Our attempts of hernia repair with polypropylene mesh were not
      successful, as the diameter of the hole in the mesh tended to enlarge with time.
      For this reason we developed a new device, which secures the desired diameter of
      the opening. The prosthesis consists of a polypropylene ring with an internal
      diameter of 20, 25 or 30 mm, mounted in the centre of a polypropylene mesh. In 14
      patients with a parastomal hernia, complicating an end colostomy, this prosthesis
      has been used. In one patient the implant had to be removed owing to infection.
      In the remaining 13 patients no recurrence or other complications have been noted
      after a median follow-up of 18 months (range 5-35 months). We conclude that the
      presented prosthetic device seems to be a useful adjunct for the local repair of
      a paracolostomy hernia.

PMID- 1402310
TI  - Pelvic recurrence after surgical treatment of rectal and sigmoid cancer. A
      prospective clinical trial on 274 patients.
AB  - The aim of this collaborative prospective study was to verify the incidence of
      pelvic recurrence (PR) after radical surgery for cancer of the rectum and
      sigmoid. Very low anterior resection (VLAR) was usually performed, with the aim
      of preserving anal function and obtaining the maximum of radicality by means of
      en bloc excision of the mesorectum. Between 1984 and 1987, 274 patients underwent
      curative surgery for rectal and sigmoid cancer, 230 (84%) of whom underwent
      anterior resection (AR) and 44 (16%) abdominoperineal resection (APR). Post
      operative mortality was 2.5%. Follow-up ranged from 24 to 72 months (mean 37 m);
      248 cases (90.5%) were included in the final prospective study. PR occurred in
      41/248 cases (16%), within 24 months in 80% of cases. PR occurred in 15.8%
      (33/208) after AR and in 20% (8/40) after APR, p = NS. Nevertheless in middle and
      low rectal tumours at stage C the incidence of PR in patients who had VLAR was
      34.5% (10/29) and 12% (3/25) in those who had APR (p < 0.05). PR rates in VLAR
      patients was 40% for stage C low rectal tumours and 54.5% for low rectal tumours
      at Astler Coller stage C2. The PR incidence for stage C1 tumours of the low
      rectum was zero after VLAR and APR, allowing the assumption that lymphnode
      metastases in non-penetrating tumours do not compromise the results when the
      mesorectum is completely excised. We can assume that the choice of VLAR as a
      substitute for APR whenever possible limits the comparison of their
      results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402311
TI  - Early postoperative contrast radiology in the assessment of colorectal
      anastomotic integrity.
AB  - The predictive value and safety of early postoperative radiological assessment of
      colorectal anastomotic integrity is controversial. In this study, 233 patients
      with colorectal or left sided colonic anastomoses had water soluble contrast
      enemas performed in the early postoperative period (mean: day 7 postoperatively,
      range: days 4-14). A total of 40 radiological leaks were recorded but only 12 of
      these patients had clinical signs of anastomotic dehiscence. Furthermore, 11
      patients who had normal contrast enemas subsequently developed a clinical
      anastomotic leak. There were therefore 28 (12.0%) false positive and 11 (4.7%)
      false negative results giving values for the specificity and sensitivity of the
      radiological investigation of 86.7% and 52.2% respectively. Only 3 patients
      (1.3%) developed a clinically apparent anastomotic complication following a
      contrast enema. We conclude that while radiological assessment of distal large
      bowel anastomoses in the early postoperative period appears to be a safe
      procedure, it provides little useful clinical information with regard to early
      postoperative morbidity. Recent work has, however, suggested that radiological
      anastomotic integrity may be relevant to long term outcome following surgery for
      colorectal cancer.

PMID- 1402312
TI  - Primary adenosquamous and squamous cell carcinoma of the colon and rectum.
AB  - Three new cases of squamous cell and adenosquamous carcinoma of the rectum are
      reported, bringing the total number of cases in the English medical literature to
      72. Each of the three patients presented with painless hematochezia. Therapy was
      by surgical resection followed by chemoradiation therapy in two patients. The
      incidence, presentation, diagnostic criteria and methods, tumor location, natural
      history, theory of etiology and management of this unusual tumor are discussed.

PMID- 1402314
TI  - Radioimmuno-guided endoscopy (RIGE) in the detection of primary and recurrent
      rectal tumor.
AB  - The usefulness of radioimmunoguided endoscopy in the detection of primary and
      recurrent rectal cancer was investigated. Of the 15 patients included in our
      study, 4 with suspected primary rectal cancer were examined preoperatively, while
      the remaining 11 were studied after radical resection of rectal carcinoma with
      the aim of detecting local recurrence. Radioimmunoguided endoscopy was performed
      employing a hand-held gamma-detecting probe (mod. 2 Oris, France), after the
      administration of a 111In labeled monoclonal antibody to CEA. Radioimmuno-guided
      endoscopy results detected the presence of primary or recurrent periluminal
      cancer in seven cases. In four it modified the preoperative stage based on the
      findings of conventional investigation and it influenced the surgical decision in
      five cases. No toxicity was noted and none of the patients developed HAMAs.

PMID- 1402313
TI  - Sodium and potassium excretion before and after conversion from conventional to
      reservoir ileostomy.
AB  - Sodium and potassium in the ileostomy output and urine were determined in 28
      patients with ulcerative colitis on a free diet and in eight patients on a
      defined constant diet, before and after conversion from a conventional ileostomy
      (CI) to a continent reservoir ileostomy (RI). Feces and urine were collected both
      in the hospital and at home. Patients with CI on free diet had a median
      intestinal loss of 62 mmol sodium and those with RI 74 mmol/24 h collected in the
      hospital (p < 0.05). The figures for at home was 79 and 81 mmol/24 respectively,
      and were larger than in the hospital (p < 0.01). Sodium loss in the urine (U-Na)
      and the intake of sodium did not change significantly after conversion. Patients
      with a low U-Na before conversion also had a low U-Na after, in a few almost nil,
      implying a need for increased intake of sodium. Patients with a CI and low
      urinary output of sodium should be carefully studied with respect to their sodium
      balance before accepting them for conversion to RI. The ileostomy output of
      potassium increased after conversion (4.3 vs. 6.8 mmol/24 h; p < 0.01) in the
      hospital (5.3 vs 7.1 mmol/24 h; p < 0.01) at home. Patients on a defined constant
      diet before and after conversion did not show any significant differences in
      absorption of sodium, potassium, magnesium or calcium after conversion, but did
      show a reduced dry weight of the ileostomy output, indicating an increased
      degradation of intestinal contents in RI patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402315
TI  - The internal anal sphincter can not close the anal canal completely.
AB  - We determined the maximum closing capability of the internal anal sphincter
      muscle ring in vitro and in vivo. The internal sphincter, 4 to 6 mm thick, cannot
      close the anal canal hermetically, not even during maximal contraction. The blood
      filled anal cushions have to fill up an intrasphincteric gap of at least 7 to 8
      mm in diameter.

PMID- 1402317
TI  - Medicine and religion.

PMID- 1402316
TI  - The value of endosonography in preoperative staging of rectal cancer.
AB  - Sixty-three patients with mobile rectal cancer were examined preoperatively with
      endorectal ultrasonography (EUS). The depth of infiltration and the presence of
      mesorectal lymph node metastases could be assessed in 53 patients. Doppler
      ultrasonography was performed in 16 cases with suspected lymph node enlargement
      in order to discriminate between lymph nodes and blood vessels. Tumour growth in
      the bowel wall was correctly estimated in 43 (81%) patients. The degree of spread
      was overestimated in five patients and underestimated in five. The evaluation of
      the mesorectal lymph node status was also accurate in 43 (81%) patients. Nine
      patients had one or several regional lymph node metastases, but the EUS revealed
      only some of the metastatic lymph nodes in each case. In the other 34, no lymph
      node metastases were found. In two patients the EUS was falsely positive since no
      lymph nodes could be demonstrated in the operative specimens. In eight patients
      the examination was falsely negative. EUS is considered to be an accurate method
      for preoperative assessment of tumour infiltration in the bowel wall as the risk
      of understaging was under 10%. Preoperative irradiation and surgery may be chosen
      based on the EUS-determined tumour extension into the rectal wall.

PMID- 1402318
TI  - ECG of the month. On U-turns. Negative U waves.

PMID- 1402319
TI  - Severe anoxic brain injury secondary to cardiac arrhythmia.

PMID- 1402320
TI  - Providing early intervention care to the newly diagnosed adult HIV positive
      patient.

PMID- 1402321
TI  - Renal metastases from papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma is the most common type of thyroid cancer. It is
      estimated that 4% to 20% of patients with papillary carcinoma will develop
      distant metastases during the course of their disease, most commonly to lung and
      bones. We describe the rare occurrence of metastatic papillary carcinoma of the
      thyroid to the kidney in a living patient that was successfully treated with a
      right radical nephrectomy and 131I with complete disappearance of all metastatic
      disease.

PMID- 1402323
TI  - Experience with a new woven prosthesis.
AB  - The search for the ideal vascular graft is a dream that has eluded surgeons for
      centuries. Since the introduction of the fabric vascular prosthesis in 1952 by
      Voorhees, Jaretzki, and Blakemore, a wide variety of materials and designs have
      been tested. Dacron has withstood the test of time in both the knitted and woven
      types. Each of these graft designs has its own advantages and disadvantages, but
      we believe that the interlock construction of the Ochsner series grafts provides
      a solution to the problems associated with the earlier woven grafts while
      maintaining the advantages of the woven construction: (1) unraveling has been
      eliminated, and fraying has been reduced by the use of the interlock stitch; (2)
      the graft has been made soft and pliable by using three low-twist yarns, avoiding
      chemical impaction of the yarns, and utilizing a loose crimp; and (3) nonfixation
      of the pseudo-intima has been corrected by using low-twist, highly filamentous
      yarns which allow ingrowth of tissue for good fixation.

PMID- 1402322
TI  - Reducing potential liability in evaluation of the breast.
AB  - One in nine women will develop breast cancer in her lifetime. It is crucial to
      evaluate the breast with a three-part approach: self breast examination, annual
      physician breast examinations, and mammography. In addition, and of equal
      importance, is proper documentation of the findings and communication between the
      physicians involved.

PMID- 1402324
TI  - Endothelial adhesivity of sickle red blood cells.

PMID- 1402325
TI  - Role of platelets in endocarditis: clues from von Willebrand disease.

PMID- 1402326
TI  - Molecular mechanisms of thrombin-induced human and bovine endothelial cell
      activation.
AB  - Thrombin, the key regulatory protein of hemostasis, is a potent stimulus for
      endothelial cell activation, a process implicated in a variety of ischemic,
      thrombotic, and inflammatory vascular disorders. Activation of the thrombin
      receptor requires a novel mechanism of receptor proteolysis generating a tethered
      receptor ligand. Synthetic peptides whose sequences are identical to this newly
      exposed receptor NH2-terminus reproduce thrombin effects on human and bovine
      endothelial cell activation. Receptor cleavage by catalytically active alpha
      thrombin is tightly coupled to a PI-PLC, with resultant generation of IP3 and
      DAG, increases in [Ca2+]i, and translocation of PKC (Fig. 3). Both the increase
      in [Ca2+]i and PKC activation are required for thrombin-stimulated PLA2 and PLD
      activity, PGI2 synthesis, and barrier dysfunction, the latter occurring as the
      result of Ca2+ and PKC effects on specific cytoskeletal protein elements and
      other contractile proteins (Fig. 3). Further investigations are ongoing to
      identify more clearly not only the precise biochemical intermediates involved in
      the endothelial cell response to thrombin but also the specific protein kinase
      systems involved in thrombin-mediated signal transduction in vascular
      endothelium.

PMID- 1402327
TI  - Involvement of phosphatidic acid, phosphatidate phosphohydrolase, and inositide
      specific phospholipase D in neutrophil stimulus-response pathways.

PMID- 1402328
TI  - Neutrophil signal transduction: calcium, kinases, and fusion.

PMID- 1402329
TI  - Rap proteins: investigating their role in cell function.

PMID- 1402330
TI  - Sickle erythrocyte adherence to large vessel and microvascular endothelium under
      physiologic flow is qualitatively different.
AB  - Complications in sickle syndromes are thought to result from regional
      disturbances of normal blood flow with subsequent ischemic damage. Adherence of
      sickle erythrocytes has been implicated in the pathophysiology of occlusive
      complications. Most previous studies have explored adherence of sickle
      erythrocytes to endothelial cells from large vessels, even though the majority of
      the pathophysiologic models implicate the microvascular system. To explore
      potential variation in endothelial interactions at low shear rates, adherence of
      sickle erythrocytes to large vessel umbilical vein endothelium and microvascular
      endothelium was compared under flow conditions in a parallel-plate flow chamber
      at a shear stress of 1.0 dyne/cm2. Autologous plasma promotes high levels of
      sickle red cell adherence to microvascular endothelial cells, but only low levels
      of adherence to human umbilical vein endothelium. On average, autologous plasma
      promotes sixfold more sickle cell red adherence to microvascular endothelial
      cells. In contrast to umbilical vein endothelium, high molecular von Willebrand
      factor does not elevate sickle cell adherence to microvascular endothelial cells,
      and the integrin receptor agonist peptide, RGD, does not inhibit adherence to
      microvascular endothelial cells. These results demonstrate that sickle
      erythrocyte adherence to large vessel and microvascular endothelium is
      quantitatively and qualitatively different and that plasma factors may have
      significant impact on sickle erythrocyte adherence to endothelium in the
      microvessels. Since microvascular occlusion has been suggested as an antecedent
      of ischemic damage in sickle syndromes, plasma enhanced adherence to
      microvascular endothelium may contribute to the pathophysiology of episodic
      occlusion in sickle cell anemia.

PMID- 1402331
TI  - Pigs with von Willebrand disease may be resistant to experimental infective
      endocarditis.
AB  - Indirect evidence suggests that the blood platelet is important in the
      pathogenesis of experimental infective endocarditis. Mechanical injury to the
      endocardial surface causes deposition of fibrin and platelets; injected
      microorganisms quickly localize to this lesion. Endocarditis pathogens also bind
      to and activate platelets. We used our previously described animal model for
      inducing infective endocarditis in normal pigs and applied it to animals with
      severe von Willebrand disease. The model uses catheter-induced trauma to the
      aortic valve and endocardium, followed by intravenous injection of group C
      streptococci. Control animals all showed typical clinical and laboratory evidence
      of endocarditis. In contrast, in pigs with von Willebrand disease (n = 4)
      endocarditis failed to develop. Studies in vitro of platelet-bacteria
      interactions showed that platelets derived from both normal and diseased pigs
      were equal in their ability to bind to and be activated by group C streptococci.
      These data suggest that normal platelet function is important in the pathogenesis
      of experimental infective endocarditis.

PMID- 1402333
TI  - Monoclonal antibody to tumor necrosis factor--alpha prevents lethal endotoxin
      sepsis in adult rhesus monkeys.
AB  - In a rhesus monkey endotoxin sepsis model established by intravenous
      administration of 300 mg/kg D-galactosamine and 0.1 microgram/kg
      lipopolysaccharide from Salmonella abortus equi, hemodynamic, respiratory,
      metabolic and hematologic variables; levels of blood gases; monkey leukocyte
      elastase levels, and blood plasma concentrations of tumor necrosis factor--alpha
      (TNF) were monitored for 6 hours after administration, and again after 24 hours.
      Thirty minutes after administration of lipopolysaccharide, either 15 mg/kg anti
      TNF monoclonal antibody (MoAB; n = 6) or vehicle placebo (saline solution; n = 4)
      were given intravenously. During this short-term experiment the organ functions
      were not different between the treatment groups. However, anti-TNF MoAb afforded
      morphologic protection from heart, lung, liver, and kidney damage after
      lipopolysaccharide challenge. Coagulation responses (platelet count and levels of
      fibrinogen, antithrombin III, and thrombin-antithrombin III complex) were smaller
      in anti-TNF MoAB-treated monkeys. Plasma TNF levels (WEHI cell cytotoxicity
      assay) reached a peak (350 pg/ml) 60 minutes after lipopolysaccharide
      administration in vehicle control subjects but no TNF was detected in the anti
      TNF MoAB-treated monkeys. All control animals died 67 +/- 30 hours after
      lipopolysaccharide administration from multiorgan failure. On the contrary, all
      anti-TNF MoAB-treated animals survived 14 days (p > 0.005 vs placebo group
      mortality). Thus in short-term monkey experiments our study indicates protection
      against lipopolysaccharide-induced endotoxin sepsis by anti-TNF MoAB, which may
      have clinical relevance for the treatment of human septicemia.

PMID- 1402332
TI  - Phosphorus 31-nuclear magnetic resonance spectroscopy of rat liver during simple
      storage or continuous hypothermic perfusion.
AB  - The adenosine triphosphate (ATP) content and intracellular pH (pHi) of isolated
      rat liver before, during, and after cold preservation in either University of
      Wisconsin lactobionate solution (UW) (n = 10) or Euro-Collins solution (EC), (n =
      8) were monitored with phosphorus 31 nuclear magnetic resonance. The 31P nuclear
      magnetic resonance spectra were obtained on a 4.7 T system operating at 81 MHz.
      Fructose metabolism, liver enzyme release, oxygen consumption, and rat survival
      after liver transplantation were also evaluated. During simple cold storage (SCS)
      the ATP level declined to undetectable levels with both preservation solutions
      whereas the pHi declined to approximately 7.0. In contrast, during continuous
      hypothermic perfusion (CHP), hepatic ATP levels remained measurable during the 24
      hour EC preservation and actually increased significantly (p > 0.01) during UW
      preservation. After reperfusion at 37 degrees C with Krebs lactate, the livers in
      SCS treated with EC differed significantly from the UW-treated livers in terms of
      their ATP level and pHi and their response to a fructose challenge. In contrast,
      livers undergoing CHP demonstrated similar behaviors with both solutions. These
      results demonstrate an increase in the hepatic ATP content during CHP, which
      occurs with UW but is not seen with EC. On the other hand, only livers that were
      simply stored with UW achieved significant survival after transplantation,
      whereas CHP livers were affected by vascular damage as demonstrated by fatal
      thrombosis after transplantation. These data suggest that ATP content is not the
      only determinant of good liver function. A system of hypothermic perfusion might
      further improve liver preservation efficacy should injury to the vascular
      endothelium be avoided.

PMID- 1402334
TI  - Cardiac anaphylaxis in the Sprague-Dawley rat.
AB  - Anaphylactic shock was induced in pentobarbital-anesthetized, mechanically
      ventilated Sprague-Dawley rats that had been sensitized 21 days earlier to
      crystallized ovalbumin. The sensitization was confirmed by passive cutaneous
      anaphylaxis test. Antigen challenge produced an immediate reduction in mean
      aortic pressure from 168 to 67 mm Hg within 1 minute after intravenous injection
      of ovalbumin. Plasma histamine increased from 4.5 to 128 ng/ml within 5 minutes
      after injection of antigen. There were no changes in airway or esophageal
      pressures after antigen challenge. Left ventricular diastolic pressure was
      increased, and contractility, as measured by the rate of change of left
      ventricular pressure (dP/dt), was decreased over an interval exceeding 90
      minutes. When isolated, constant flow--perfused hearts from sensitized Sprague
      Dawley rats were challenged with antigen, decreases in left ventricular function
      were observed associated with decreased positive and negative maximum rate of
      change of left ventricular pressure (dP/dtmax). This experimental model in the
      rat therefore demonstrated selective myocardial impairment with reduced
      inotropism and lusitropism after anaphylaxis.

PMID- 1402335
TI  - Identification of two zinc metalloendopeptidases in alveolar macrophages of rats,
      guinea pigs, and human beings.
AB  - Neutral endopeptidases EC 3.4.24.11 and EC 3.4.24.15, widely distributed zinc
      metalloendopeptidases, degrade a number of biologically active peptides including
      substance P, bradykinin, neurotensin, and luteinizing hormone-releasing hormone.
      In this study we measured EC 3.4.24.11 and EC 3.4.24.15 activity in alveolar
      macrophages, key inflammatory cells in the lung that produce and respond to a
      large number of bioactive substances including chemotactic peptides, with the
      substrates glutaryl-ala-ala-phe-2-naphthylamide and tertiary butoxycarbonyl-phe
      ala-ala-phe-paraaminobenzoate, respectively. We found that specific activity of
      EC 3.4.24.15, defined as activity inhibited with N-[(1RS)-carboxy-3-phenylpropyl]
      ala-ala-phe-paraaminobenzoate+ ++, was significantly higher (p < 0.001) in cells
      from Sprague-Dawley rats (485 +/- 123 nmol/mg protein.hr) than in cells from
      Hartley guinea pigs (138 +/- 94 nmol/mg protein.hr), healthy human male smokers
      (121 +/- 73 nmol/mg protein.hr) and healthy human male nonsmokers (94 +/- 12). In
      contrast, activity of EC 3.4.24.11, defined as activity inhibited with N-[(1RS)
      carboxy-3-phenylpropyl]-phe-paraaminobenzoate, was significantly higher (p <
      0.001) in cells from human smokers (689 +/- 167 nmol/mg protein.hr) and
      nonsmokers (762 +/- 136 nmol/mg protein.hr) than in cells from rats (52 +/- 12
      nmol/mg protein.hr) and guinea pigs (34 +/- 14 nmol/mg protein.hr). An additional
      activity in alveolar macrophages toward tertiary butorycarbonyl-phe-ala-ala-phe
      paraaminobenzoate was inhibited with L-3-carboxy-trans-2,3-epoxypropionyl
      leucylamido-(4-guanido) butane, a specific inhibitor of cysteine proteinases, a
      finding of interest because in general enzymes in this class show little activity
      at neutral pH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402336
TI  - In vivo studies of biliary ceftriaxone excretion and solubility in guinea pig
      hepatic bile.
AB  - Ceftriaxone (CFTX), a third-generation cephalosporin, has occasionally been
      reported to produce biliary sludge composed of its calcium salt. We performed
      studies in guinea pigs to (1) investigate the hepatic route of CFTX excretion,
      (2) determine ceftriaione's effects on bile flow and composition, and (3)
      quantify the solubility and metastability of the calcium salt as a function of
      administered dose. Our results show that even at high doses ceftriaxone has only
      minimal effects on bile flow and biliary electrolyte secretion, either alone or
      in combination with bile salt (taurocholate) infusion. A significant increase in
      total calcium concentration was observed without change in free Ca2+
      concentration, this is compatible with formation of a soluble calcium salt of
      ceftriaxone, as previously demonstrated in vitro. Ion products of Ca2+ and
      ceftriaxone as high as 3.5 times the solubility product constant without crystal
      formation were observed, confirming the presence of a metastable state for the
      calcium salt of ceftriaxone in the living animal. Biliary excretion of
      ceftriaxone inhibited excretion of indocyanine green, suggesting that ceftriaxone
      and indocyanine green share a common anionic excretory pathway in this species.

PMID- 1402337
TI  - Distribution of erythrocyte free porphyrin content in erythropoietic
      protoporphyria.
AB  - Erythrocytes of patients suffering from erythropoietic protoporphyria (EPP)
      contain high levels of unchelated protoporphyrin IX (PP) molecules when they
      enter circulation, and the leakage of PP that leaks from the circulating cells is
      responsible for the patients' cutaneous photosensitivity. The level of PP in EPP
      blood has long been used as an indicator of the severity of the disease and is
      useful in its management. The present study investigates what additional
      information may be obtained by determining the distribution of the PP content of
      individual EPP red cells. Absorption and fluorescence images of fields of the
      dispersed and immobilized red cells from nine patients with EPP were acquired
      under computer control by use of an inverted fluorescence microscope equipped
      with a cooled slow-scan charge-coupled device camera. The distribution functions
      of the fluorescence emitted by individual red blood cells (IRBC) were derived by
      a suitable image analysis program and were converted to the distributions of the
      cellular PP content by relating the average value of the distributions (Iav) to
      the PP level of packed cells, as determined by an extraction assay. The IRBC
      distributions show that a small percentage of the red cells is responsible for
      most of the PP fluorescence, and the distributions of IRBC/Iav for the nine
      patients with EPP were found to be very similar. This is consistent with the
      leakage rate during circulation being approximately proportional to the cells' PP
      content.

PMID- 1402338
TI  - Urinary calcium excretion in essential hypertension.
AB  - Patients with essential hypertension have been reported to have higher levels of
      urinary calcium excretion (UCaV) than normotensive persons. We tested the
      hypothesis that the calciuria of hypertension is due to dietary factors and
      evaluated several alternate mechanisms. UCaV was studied in 15 patients with
      essential hypertension compared with 16 age- and gender-matched normotensive
      control subjects. For subjects taking self-selected, free-living diets, the
      difference in UCaV between normotensive (130 +/- 14 mg/day) and hypertensive
      subjects (201 +/- 37 mg/day) was not significant (p = 0.1). However, in a
      controlled diet with moderately restricted sodium intake (88 mEq), urinary
      calcium excretion was significantly higher (p = 0.02) in the hypertensive than in
      the normotensive group receiving 400 mg calcium (204 +/- 25 vs 132 +/- 13 mg/day)
      and 1400 mg calcium (272 +/- 31 vs 187 +/- 25 mg/day). Twenty-four-hour UCaV was
      directly and significantly correlated with blood pressure (r = 0.63 for standing
      systolic blood pressure; p < 0.001). A 1000 mg oral calcium load caused similar
      changes in UCaV (0.12 +/- 0.11 vs 0.12 +/- 0.07 mg per 100 ml glomerular
      filtration) and serum ionized calcium level (0.06 +/- 0.08 vs 0.06 +/- 0.02
      mmol/L) in normotensive and hypertensive subjects, respectively, suggesting that
      there was no difference in intestinal calcium absorption between the groups.
      Fasting UCaV did not differ between the hypertensive (8.9 +/- 4.5 mg per 2 hours)
      and normotensive groups (10.9 +/- 11.5 mg per 2 hours).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402339
TI  - Cirrhosis impairs serum bacteriostasis for Escherichia coli.
AB  - To study the effects of cirrhosis on serum inhibition of Escherichia coli,
      cirrhosis with ascites was induced in male Sprague-Dawley rats by intragastric
      administration of carbon tetrachloride. Heat-inactivated (56 degrees C for 30
      minutes) serum from cirrhotic rats (CRS) or that from control rats (NRS) was
      inoculated with 1 x 10(5) colony-forming units per milliliter (CFU/ml) of E.
      coli, and growth was measured after 24 hours. The mean growth of E. coli in CRS
      was significantly higher than growth in NRS: 3.5 +/- 5.4 x 10(8) CFU/ml versus
      1.2 +/- 2.0 x 10(6) CFU/ml, respectively (p < 0.01). Fifty-four percent of CRS
      samples (22/41) completely lacked bacteriostatic activity. These CRS samples were
      categorized as growth-supporting (G+CRS) because their growth exceeded the mean +
      2 SD of NRS (5.2 x 10(6) CFU/ml). Serum bacteriostasis could be restored to G+CRS
      by adding purified rat apotransferrin (1 mg/ml), suggesting the presence of
      excess iron in G+CRS. However, serum iron concentration (SI) and total iron
      binding capacity (TIBC) were virtually the same in G+CRS (SI = 120 +/- 22
      micrograms/dl; TIBC = 351 +/- 45 micrograms/dl) as in growth-inhibitory CRS (SI =
      131 +/- 16 micrograms/dl; TIBC = 347 +/- 46 micrograms/dl) but were significantly
      less than NRS (SI = 208 +/- 29 micrograms/dl; TIBC = 533 +/- 57 micrograms/dl), p
      < 0.01. The percent transferrin saturation was similar in all groups: 34% +/- 6%;
      38% +/- 5% and 39% +/- 9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402340
TI  - Bone response to invading tumors with spindle cell components: a report of
      findings in two patients.
AB  - Two case studies are presented in which quantitative bone histomorphometry is
      used to analyze bone changes in adult patients with diagnosed spindle cell
      sarcoma. Three tumor-involved sites and one noninvolved site from the iliac crest
      of patient 1 were evaluated. In the involved sites the percentage trabecular bone
      volume (11.0%) and the number of osteoblasts (0.6 cell/mm2) were significantly
      reduced, osteoid volume was significantly increased (8.1%), and woven osteoid was
      present. The total eroded surface (6.8%) was also significantly increased. In the
      noninvolved site the number of osteoblasts was decreased and both the percentage
      eroded and percentage osteoclast surfaces were increased. In the femoral
      epicondyle specimen from patient 2 the number of osteoblasts was 27.0 cells/mm2,
      percentage osteoid volume was 18.4%, percentage osteoid surface was 62.9%, and
      osteoid thickness was 20.0 microns. In tumor-involved sites in both patients
      indices of active bone resorption were similar and normal. These two case studies
      indicate that (1) distinctive morphologic changes occur in bone invaded by
      spindle cell sarcoma, and that (2) changes affect bone formation to a greater
      extent than bone resorption. Bone alterations are probably local in nature and
      related to the extent and duration of tumor invasion and the influence of local
      tumor factor(s).

PMID- 1402341
TI  - Inhibitory effect of platelet factor 4 (PF4) on the growth of human
      erythroleukemia cells: proposed mechanism of action of PF4.
AB  - The effect of platelet factor 4 (PF4) on the growth of human erythroleukemia cell
      line (HEL) and the binding characteristics of iodine 125-labeled PF4 to cells
      were studied to determine the mechanism of action of PF4. HEL cells were
      cocultured with various doses of PF4 in either a plasma clot system for colony
      assay or a liquid system for tritiated thymidine incorporation. A significant
      inhibition of HEL colony growth and tritiated thymidine incorporation was seen at
      PF4 doses of 1 microgram/ml and 0.5 microgram/ml, respectively. The inhibitory
      effect of PF4 could be abrogated by the addition of heparin (5 to 10
      micrograms/ml). Enzyme-linked immunosorbent assay showed that PF4 had no obvious
      effect on the expression of platelet glycoprotein IIb/IIIa of HEL cells. Binding
      of 125I-PF4 to HEL cells reached equilibrium within 20 to 30 minutes with
      dissociation constant of 1.3 x 10(-10)M and Bmax of 6.3 pmol/10(5) cells and was
      inhibited by an excess of unlabeled PF4, beta TG, and heparin but was not
      affected by PMA, IL-3, IL-6, GM-CSF, and interferon-alpha. PF4 did not affect the
      binding of 125I-IL-3 and 125I-IL-6 to HEL cells. These data demonstrate that PF4
      inhibits the growth of HEL cells by specific binding to HEL cells and suggest
      that the action of PF4 may be associated with the heparin-binding sites of the
      molecule.

PMID- 1402342
TI  - Extraerythrocytic hemoglobin, heme, and procoagulant activity.

PMID- 1402343
TI  - Inaugural address: Health care affordability and accessibility.

PMID- 1402344
TI  - Blood pressure changes in patients with chronic obstructive pulmonary disease and
      hypertension completing phase II pulmonary rehabilitation.
AB  - A retrospective study was conducted evaluating the resting blood pressure (BP) of
      160 patients at the onset and upon successful completion of a Phase II pulmonary
      rehabilitation program. Patients with chronic obstructive pulmonary disease
      (COPD) exercise at submaximal loads. Patients with both hypertension and COPD
      would remain hypertensive after a course of pulmonary rehabilitation. The two
      tailed t-test was utilized to compare BP at the onset to BP at the completion of
      the program. No significant differences were found in the following groups: (1)
      Start and end SBP or DBP of all patients; (2) Start and end SBP or DBP of the 40
      (25%) hypertensive patients (HTN-Pts); (3) Start and end SBP or DBP of the 6 (4%)
      HTN-Pts on antihypertensive (anti-HTN) medications; (4) Start and end SBP or DBP
      of the 34 (21%) HTN-Pts off anti-HTN medications. This study supports the
      hypothesis that HTN-Pts with COPD participating in a Phase II pulmonary rehab
      program remain hypertensive. Hypertension in this population should be treated
      medically.

PMID- 1402345
TI  - Treatment of traumatic pancreatic pseudocyst by percutaneous aspiration.
AB  - We describe the nonoperative management of a traumatic pancreatic pseudocyst
      following blunt trauma in a child. This problem can be accurately diagnosed and
      followed with computed tomography or ultrasound. Percutaneous aspiration of
      unilocular pancreatic pseudocysts in children provides an attractive alternative
      to operative treatment in selected cases.

PMID- 1402346
TI  - Maternal mortality report.

PMID- 1402347
TI  - Community classrooms.

PMID- 1402348
TI  - William B. Monnig, MD, KMA's president 1992-3. Interview by Sue Tharp.

PMID- 1402349
TI  - Meeting the needs of the 21st century--through programs of awareness and
      education.

PMID- 1402350
TI  - Pseudo pericardial rub.

PMID- 1402351
TI  - Bronchoscopy for pulmonary hygiene in the intensive care unit.
AB  - The safety and ease of fiberoptic bronchoscopy recommends its use in the
      intensive care unit. In critically ill patients, the procedure may be a valuable
      diagnostic or therapeutic tool. In most instances, the diagnostic indications are
      well defined. The therapeutic indications for bronchoscopy, however, are more
      controversial. They center around using the bronchoscope for removal of
      secretions, mucus plugs and reversing atelectasis in mechanically ventilated
      patients. This report examines the small but definite risk of therapeutic
      bronchoscopy in mechanically ventilated patients.

PMID- 1402352
TI  - Kentucky's bicentennial and a brief overview of 200 years of medical practice and
      the physician. 2.

PMID- 1402353
TI  - Address by the president of the Kentucky State Medical Society. 1852.

PMID- 1402354
TI  - Golden spikes. 1951.

PMID- 1402355
TI  - Ear, nose and throat in ancient Egypt.

PMID- 1402356
TI  - Long-term results of total ossicular chain reconstruction using autografts.
AB  - The long-term results of 63 total ossicular chain reconstructions using
      autografts is presented. The follow-up period ranged from 18 months to 18 years
      with an average of 8.5 years. The primary aims of the study were firstly to
      assess the long-term success rate and to find out if there were any hitherto
      unknown causes of bone graft failure. In the event, it was found that the
      recently described anatomical variation of the oval window viz., the deep oval
      window, was the prime cause of failure in 32 per cent of unsuccessful cases. Some
      measures to help to mitigate this problem, are suggested. The result were
      assessed on the basis of: 1. A minimum gain of 20 dB HL in air conduction
      (Technical success). The success rate was 55.5 per cent. 2. Patients benefited
      using Smyth and Patterson's criteria in conjunction with the Glasgow Benefit
      Plot; 54 per cent of the patients benefited significantly.

PMID- 1402357
TI  - Nasal polypectomy: should antral washout be a routine?
AB  - Seventy patients with nasal polyps were studied. Forty-seven of these had pre
      operative sinus radiographs and all seventy patients had antral washouts at the
      time of nasal polypectomy. One hundred and seventeen antral aspirates were sent
      for culture and microscopy. The naked eye appearance of aspirates were turbid in
      34 patients. Bacteria were cultured from 15 of the specimens in 10 patients. It
      was concluded that antral washout should be recommended in all patients who have
      nasal polypectomy and that there is no need for sinus radiographs in those
      patients who have uncomplicated nasal polyps.

PMID- 1402358
TI  - Antroscopy in rhinoscleroma.
AB  - Rhinoscleroma is a chronic specific granulomatous inflammatory condition that has
      an affinity to the mucosa of the upper respiratory tract. Involvement of
      maxillary antrum is said to be very uncommon. In the present study antroscopy was
      performed in 20 patients with rhinoscleroma to find out the type, nature and site
      of the lesion in the maxillary antrum. The maxillary antrum was involved in 60
      per cent of cases with rhinoscleroma. The lesions occurred in the form of
      atrophic changes, granuloma, and the fibrotic thick healed stage. The anterior
      inferior part and medial wall of the antrum are found to be more commonly
      affected. It is suggested that involvement of maxillary antrum in scleroma may
      act as a reservoir of infection and such patients may therefore take a longer
      time to respond to antibiotic therapy.

PMID- 1402359
TI  - Treatment of allergic and vasomotor rhinitis by the local application of
      different concentrations of silver nitrate.
AB  - In 1980, Bhargava et al. reported a new treatment of allergic and vasomotor
      rhinitis by the local application of 15 per cent silver nitrate. The results of
      further studies of the treatment by using different concentrations of silver
      nitrate ranging from 5 per cent to 25 per cent and normal saline as placebo are
      presented here; 15 per cent has been found to be the most effective concentration
      giving successful results in 75.7 per cent of cases. It is applied to the
      anterior portion of both inferior turbinates and the anterior part of the nasal
      septum once a week on five occasions. Best relief was obtained from the most
      annoying symptoms of sneezing and rhinorrhoea. Asthma was controlled in 50 per
      cent of such patients who had attacks of allergic rhinitis followed by asthma.
      For this widely prevalent disease, the treatment was found to be simple, easy and
      useful, with negligible side-effects.

PMID- 1402360
TI  - Radiological and endoscopic study of the maxillary sinus in primary atrophic
      rhinitis.
AB  - The maxillary sinuses of 40 patients suffering from primary atrophic rhinitis
      (ozaena) were studied radiologically, antroscopically and histopathologically.
      Sixty per cent of the patients showed thick bony walls and a small cavity of the
      maxillary sinus on X-ray and on antroscopy. On the other hand, 25 per cent of the
      cases revealed signs of infection including mucopurulent secretion on antroscopy
      associated with corresponding histopathological changes. It is concluded that
      poor pneumatization of the antrum plays a more important role in the pathogenesis
      of ozaena than infection.

PMID- 1402361
TI  - Is injectable collagen truly safe?
AB  - Most patients have no response to injectable collagen or silicone, but some cases
      may have positive or 'undersea' (= clinically negative but immunologically
      positive) response to collagen. From the results of the Macrophage migration
      inhibition test, the relative immunogenicity was augmented most when we used
      implants with the following combination. The first immunization was collagen and
      the second one was collagen with silicone. The augmented antigenicity might be
      enough to cause an allergic reaction to the patients who had no response to each
      implant alone.

PMID- 1402362
TI  - Flexible nasopharyngoscopy for fish bone removal from the pharynx.
AB  - The use of flexible nasopharyngoscopy with biopsy forceps for the removal of fish
      bones found in the oropharynx and hypopharynx is described. One hundred and sixty
      eight patients with ingested fish bones in the upper aero-digestive tract were
      studied over a 12-month period. Of these, 73 per cent were removed per-orally, or
      by indirect laryngoscopy. Fifteen per cent were removed using the fibreoptic
      nasopharyngoscope. Twelve per cent required a general anaesthetic and rigid
      oesophagoscopy for removal of fish bones at or below the level of the
      cricopharyngeus muscle. The technique has proven to be quick, well tolerated and
      low in morbidity. It is invaluable in patients in whom indirect laryngoscopy is
      unsatisfactory.

PMID- 1402363
TI  - Few surgical complications after 5,000 to 6,500 cGy pre-operative irradiation for
      carcinoma of the tongue.
AB  - Twenty-four patients with squamous cell carcinoma of the tongue were treated with
      5,000 cGy to 6,500 cGy pre-operative irradiation. Surgery usually consisted of
      resection of the tongue, possibly the floor of mouth, and modified or radical
      neck dissection. Musculocutaneous flaps for reconstruction were used in three
      cases and a forearm flap in one case. Despite the high radiation dose, no major
      difficulties were encountered at surgery or during the convalescence period,
      except for one osteoradionecrosis of the mandible, which was successfully treated
      by microvascular osteomyocutaneous grafting. Residual carcinoma was seen on
      histological examination of the excised tissue in 9 out of 18 (50 per cent)
      patients who received > or = 6,000 cGy, and in 4 out of 6 (67 per cent) patients
      who received about 5,000 cGy tumour dose. The 2-year crude survival rate was 65
      per cent. The data suggest that high dose pre-operative irradiation is feasible
      and does not compromise surgical treatment.

PMID- 1402364
TI  - Complications of treatment of recurrent laryngeal papillomatosis with the carbon
      dioxide laser in children.
AB  - A retrospective study of the complications of treatment with the carbon dioxide
      (CO2) laser of 17 patients diagnosed to be suffering from recurrent laryngeal
      papillomatosis is presented. No immediate complications occurred except one case
      of laryngospasm and failure to intubate during anaesthesia leading to hypoxic
      encephalopathy. Three patients were completely free from disease and
      complications. Another patient was free from laryngeal lesions but developed a
      papilloma in the right tonsillar pillar. Five other patients showed one or more
      multiple sites of involvement in addition to the larynx. Laryngeal scarring
      developed in ten patients. Six patients (35.29 per cent) developed scarring as
      anterior glottic webs while in two scarring (11.7 per cent) occurred as posterior
      glottic webs. One developed scarring in the supraglottic region. The remaining
      one had scarring in both the glottic and supraglottic regions. One patient
      developed tracheal scarring necessitating laryngo-tracheal separation. Two
      patients were psychologically disturbed during treatment requiring psychiatric
      consultation and therapy.

PMID- 1402365
TI  - The open access ENT casualty service.
AB  - The ENT specialist's experience of emergencies is usually influenced by a process
      of prior selection in the GP surgery or in a general Casualty Department. A
      survey of 1,000 consecutive patients presenting to a 24 hour open access ENT
      Casualty service is presented. For a variety of reasons, over half of these
      patients had never sought their G.P.'s advice for their ENT complaint but
      preferred the hospital service. The value of even a brief exposure to ENT
      casualty work for GP trainees is demonstrated.

PMID- 1402366
TI  - Difficult diagnostic laryngoscopy and bronchoscopy aided by the laryngeal mask
      airway.
AB  - A case of difficult diagnostic rigid bronchoscopy is described. However, flexible
      fibrescopy could be easily performed through a laryngeal mask airway despite
      complete lack of experience by the operator. Excellent visualization of the
      larynx and bronchial tree with minimal haemodynamic disturbance accompanied the
      technique.

PMID- 1402367
TI  - Tracheostomy self care: the Nottingham System.
AB  - Tracheostomy self care at home can be a problem for some patients. The Nottingham
      System attributes a competence ratio to each patient. Those liable to develop
      problems can be identified early and the appropriate support provided. The
      Nottingham System is described.

PMID- 1402368
TI  - Darier's disease of the external ear.
AB  - Darier's disease is a hereditary dermatological condition characterized by
      crusted papules distributed over the seborrhoeic areas of the trunk and head. A
      case of Darier's disease presenting to the Otolaryngology department because of
      severe involvement of the pinna is reported. The typical histological appearances
      are described and treatment discussed.

PMID- 1402369
TI  - Maxillary sinus fusariosis in immunocompetent hosts.
AB  - We report the first known cases of Fusariosis of maxillary sinus with granuloma
      and oro-antral fistula in two immunocompetent hosts. Fusarium solani was
      demonstrated in the direct microscopic examination and isolated in heavy growth
      from the biopsy materials. Both these patients were successfully treated with
      oral ketoconazole (200 mg daily) for three weeks followed by a Caldwell-Luc
      operation. Ketoconazole was continued for two months post-operatively.

PMID- 1402370
TI  - Acute stridor due to bilateral vocal fold paralysis as a presenting sign of
      myasthenia gravis.
AB  - We describe a case of myasthenia gravis in a 46-year-old man presenting as acute
      stridor with bilateral abductor paralysis of the vocal folds. Prompt diagnosis
      and medical treatment with pyridostigmine avoided the need for tracheostomy. It
      is important to remember the possibility of myasthenia gravis in cases of stridor
      due to bilateral vocal fold paralysis, since effective medical treatment is
      available.

PMID- 1402371
TI  - Tracheal reconstruction using a composite microvascular temporoparietal fascia
      flap and nasal septal graft.
AB  - The successful repair of a crushed cervical trachea using a composite
      microvascular graft is presented. The patient has been without a tracheostomy for
      four years.

PMID- 1402372
TI  - Management of acute dilatation of the oesophagus presenting as stridor.
AB  - Acute dilatation of the oesophagus causing stridor is rare. A case is presented
      and the literature is reviewed with emphasis on the management of this problem.

PMID- 1402373
TI  - Ectopic thyroid mass adherent to the oesophagus.
AB  - A 51-year-old female presented with a sensation of a lump in the throat for five
      months. Clinical examination was normal. The barium swallow and the CT scan
      showed a well-defined mass to the left of the upper oesophagus and behind it. The
      mass was removed surgically and shown pathologically to be a nodule of ectopic
      thyroid tissue. This very rare pathology is discussed together with a review of
      the relevant literature.

PMID- 1402374
TI  - Malignant parotid salivary gland peripheral nerve sheath tumour in a twelve-year
      old girl.
AB  - A case of a malignant parotid salivary gland nerve sheath tumour is reported in a
      12-year-old girl who developed a right parotid mass. Initial incisional biopsy
      showed a tumour with a mesenchymal spindle cell appearance. Immunohistochemical
      studies showed positive staining of tumour cells for vimentin and focally for S
      100 protein. These features together with ultrastructural evidence of basal
      lamina material suggested that the tumour was of nerve sheath origin. After
      subtotal parotidectomy the tumour metastasised to cervical lymph node and lung.
      There was evidence of a partial response to chemotherapy. A detailed illustrated
      histopathological description of the tumour is given.

PMID- 1402375
TI  - Management of an unusual presentation of foreign body aspiration.
AB  - Foreign body aspiration is a very common problem in children and toddlers and
      still a serious and sometimes fatal condition. We are reporting on a 2-year-old
      white asthmatic male who choked on a chick pea and presented with subcutaneous
      emphysema, and on chest X-ray with an isolated pneumomediastinum but not
      pneumothorax. On review of the literature an isolated pneumomediastinum without
      pneumothorax was rarely reported. This presented a challenge in management mainly
      because of the technique that we had to use in order to undergo bronchoscopy and
      removal of the foreign body. Apnoeic diffusion oxygenation was used initially
      while the foreign body was removed piecemeal, and afterwards intermittent
      positive pressure ventilation was used. The child did very well, and his
      subcutaneous emphysema and pneumomediastinum remarkably improved immediately post
      surgery.

PMID- 1402376
TI  - Bilateral internal jugular phlebectasia.
AB  - Internal jugular phlebectasia is a venous anomaly commonly presenting as a
      unilateral neck swelling in children. The clinicopathology, aetiology and
      management are discussed. Bilateral doppler ultrasonography is the diagnostic
      investigation of choice and should be performed in all suspected cases.
      Conservative management of the bilateral case is recommended.

PMID- 1402377
TI  - Learning disabilities: the challenges of adulthood.

PMID- 1402378
TI  - Promoting access, accommodations, and independence for college students with
      learning disabilities.
AB  - This article focuses on the four primary issues that directly affect service
      delivery to students with learning disabilities in postsecondary settings,
      including (a) How are high school and post-secondary settings different? (b) How
      are eligibility and access determined? (c) How are reasonable accommodations
      determined? and (d) How can the independence level of college students with
      learning disabilities be fostered? Each of these issues will be discussed within
      the context of the student's transition from high school, where Public Law 94-142
      is in effect, to college, where Section 504 of the Rehabilitation Act of 1973
      applies.

PMID- 1402379
TI  - The success of college students with learning disabilities: factors related to
      educational attainment.
AB  - This study reports on the educational attainment of 62 college students with
      learning disabilities as compared to a sample of 58 peers matched on gender and
      ACT composite score (+/- 1 point or exact match). All students were native
      English speakers and were enrolled as degree candidates in a small, competitive,
      private, midwestern college. Groups were compared on age, high school preparation
      and performance, college grades, GPA at the end of each year of study, graduation
      and academic failure rate, and time taken to complete degree. Factors that may
      have influenced outcomes are discussed as are implications for college admissions
      officers, college students with learning disabilities, service providers, and
      academic advisors.

PMID- 1402380
TI  - Learning disabilities and vocational rehabilitation.
AB  - Students with learning disabilities have received services in special education
      programs for many years. Unfortunately, many of these students continue to need
      services after they exit high schools. Vocational rehabilitation has begun to
      provide services for young adults with learning disabilities; however, there
      continues to be a discrepancy between the number of adults with learning
      disabilities who need vocational rehabilitation services and those who are
      receiving them. This article describes the definitions and eligibility criteria
      used by vocational rehabilitation agencies to serve adults with learning
      disabilities. By understanding the vocational rehabilitation system, teachers, it
      is hoped, will be better able to access these services for their students with
      learning disabilities.

PMID- 1402381
TI  - The postschool adjustment of persons with learning disabilities: current status
      and future projections.
AB  - Recent research on the adult status of individuals with learning disabilities was
      reviewed. It was found that learning disabilities persist into adulthood, that
      manifestations of learning disabilities in adulthood are different than in
      childhood, and that many adults with learning disabilities are not independent or
      self-sufficient. These findings are related to the changes American society is
      currently undergoing, particularly changes in the workplace. Implications for
      teachers are discussed.

PMID- 1402382
TI  - Autonomy and competence as motivational factors in students with learning
      disabilities and emotional handicaps.
AB  - Over 450 students (136 elementary, 321 junior and senior high school) with
      primary handicapping codes of learning disability (LD) or emotional handicap (EH)
      completed several questionnaires. All participants were from self-contained
      classrooms of a state-operated special education system. Questionnaires assessed
      students' self-perceptions and perceptions of home and classroom contexts, with
      all variables theoretically reflecting either the competence or the autonomy
      aspects of internal motivation or students' personal adjustment. Math and reading
      standardized achievement test scores were obtained from school records. Using
      multiple regression analyses, students' achievement and adjustment were predicted
      from the motivationally relevant self-perception and perception-of-context
      variables. Interestingly, different patterns of relations emerged for the
      students with LD and EH.

PMID- 1402383
TI  - Access to health care and the undocumented alien.

PMID- 1402384
TI  - HIV-positive health care workers and the obligation to disclose. Do patients have
      a right to know?

PMID- 1402385
TI  - Leukocyte biology: from molecular mechanisms into clinical frontier. Society for
      Leukocyte Biology 29th national meeting. Charleston, South Carolina, December 2
      5, 1992.

PMID- 1402386
TI  - Enhancement of murine macrophage binding of and response to bacterial
      lipopolysaccharide (LPS) by LPS-binding protein.
AB  - We have studied the effects of highly purified rabbit lipopolysaccharide (LPS)
      binding protein (LBP) on the ability of murine bone marrow-derived macrophages to
      respond to bacterial LPS. Macrophage responses studied include the secretion of
      tumor necrosis factor alpha, production of arginine-derived nitrite (NO2-), and
      killing of an intracellular pathogen, Leishmania enriettii. Macrophages from
      either CBA or LPS-hyporesponsive C3H/HeJ mice exhibited significantly greater
      sensitivity to LPS in the presence of LBP. Furthermore, both CBA and C3H/HeJ
      macrophages demonstrated an LBP-dependent enhancement of LPS binding. These
      results suggest that C3H/HeJ macrophages are capable of binding LPS-LBP complexes
      and support the hypothesis that hyporesponsiveness in this strain involves a step
      subsequent to LPS binding. Furthermore, these findings provide additional
      evidence of the important role played by the acute-phase plasma protein LBP in
      modifying host response to LPS.

PMID- 1402387
TI  - Treatment of murine macrophages with interferon-gamma inhibits their ability to
      bind leishmania promastigotes.
AB  - The binding of leishmania promastigotes to macrophages pretreated with interferon
      gamma (IFN-gamma) was compared to binding to untreated (resident) cells. IFN
      gamma-treated macrophages bound fewer leishmania promastigotes than did untreated
      cells. The decreased binding was apparent over a wide dose range of parasite
      inocula when the assays were performed in the absence of exogenous complement.
      This decrease was specific to leishmania, since treated and untreated macrophages
      bound comparable amounts of immunoglobulin G- and complement-coated sheep red
      blood cells. Decreased parasite binding occurred early in the macrophage
      activation pathway. Pretreatment of macrophages with IFN-gamma for as little as 6
      h, a time insufficient to induce other macrophage activation parameters,
      significantly reduced their ability to bind leishmania promastigotes. To
      determine the mechanism of this decreased phagocytosis by activated cells,
      macrophages were pretreated with specific inhibitors before the addition of
      leishmania. The binding of promastigotes to untreated (resident) macrophages was
      inhibited by approximately 50% by reagents that blocked either of two macrophage
      receptors, complement receptor type 3 (Mac-1) or a leishmania species-specific
      lectin-like receptor. Binding to IFN-gamma-treated macrophage populations, in
      contrast, was substantially inhibited only by antibody to Mac-1. Saccharides that
      were 50% inhibitory in the resident cell population, decreased binding by less
      than 10% in activated cells. The lack of saccharide inhibition by IFN-gamma
      treated cells was also reflected in an inability of activated macrophages to bind
      to beads coated with purified leishmania lipophosphoglycan (LPG). These LPG
      coated beads bound well to resident macrophages but poorly to activated cells.
      Thus, leishmania bind to macrophages by two distinct mechanisms, one that
      utilizes Mac-1 and a second mechanism that does not depend on complement and is
      saccharide inhibitable. These two binding mechanisms are distinct and
      differentially regulated in resident and activated cells.

PMID- 1402389
TI  - Lipopolysaccharide impairs macrophage cytoplasmic pH regulation under conditions
      simulating the inflammatory microenvironment.
AB  - Within the acidic inflammatory milieu, macrophages (m phi s) must maintain their
      cytoplasmic pH (pHi) within a range conducive to optimal function. It was
      previously shown that metabolism of L-arginine at concentrations present in vitro
      in RPMI medium (1.14 mM) impairs the ability of m phi s to regulate pHi. However,
      concentrations of L-arginine in vivo reportedly range from approximately 100
      microM in serum to less than or equal to 50 microM in wounds. To investigate the
      potential in vivo relevance of this inhibition, m phi pHi regulation was examined
      following incubation with low concentrations of L-arginine that mimic the
      inflammatory microenvironment, in the presence or absence of lipopolysaccharide
      (LPS). pHi regulation was evaluated as the ability of thioglycolate-elicited
      murine peritoneal m phi s to recover from an imposed cytoplasmic acid load. The m
      phi pHi was measured using a pH-sensitive fluorescent probe. Following incubation
      for 2 h in the absence of LPS, the pHi recovery rate was equivalent in cells
      incubated with and without L-arginine. Coincubation with LPS, however, resulted
      in marked inhibition of pHi recovery at L-arginine concentrations as low as 12.5
      microM. The inhibition was not due to LPS alone, since LPS without L-arginine was
      not inhibitory. Inhibition of pHi recovery was observed at LPS concentrations
      ranging from 10 ng/ml to 10 micrograms/ml. The L-arginine-dependent inhibition
      was apparent within 60 min of exposure to LPS, in both freshly harvested cells
      and cells preincubated for 2 h in the absence of L-arginine and then exposed to
      both L-arginine and LPS. Under conditions mimicking the in vivo setting, LPS
      stimulated L-arginine metabolism impairs m phi pHi regulation. Modulation of pHi
      by this mechanism may compromise m phi function within the acidic
      microenvironment of inflammation.

PMID- 1402388
TI  - Production of macrophage colony-stimulating factor by adult murine parenchymal
      liver cells (hepatocytes).
AB  - The activity of macrophage colony-stimulating factor (M-CSF) was found in the
      culture supernatant of mouse parenchymal liver cell fractions in a bone marrow
      colony-forming assay. The activity of an M-CSF-like substance purified by a four
      step procedure was neutralized by goat anti-mouse M-CSF antiserum. M-CSF mRNA was
      detected in cellular RNA prepared from cultured parenchymal liver cell fractions
      by Northern blot analysis and also in cultured parenchymal liver cells by in situ
      hybridization. These results indicate that parenchymal liver cells have the
      capacity to produce M-CSF. We discuss the role of M-CSF in hematopoiesis, the
      immune response, and other biological phenomena.

PMID- 1402390
TI  - Exudation of proliferative macrophages in local inflammation in the peritoneum.
AB  - Thioglycollate (TG)-elicited peritoneal macrophages (m phi s) were highly
      proliferative and formed m phi colonies in vitro in the presence of m phi colony
      stimulating factor (M-CSF), while resident peritoneal m phi s did not. To
      determine whether such proliferative m phi s are immigrant or locally activated
      resident m phi s, mice depleted of bone marrow cells and circulating monocytes by
      bone-seeking radiostrontium (89Sr) were injected intraperitoneally with TG. For
      control (88Sr) and splenectomized (Spx) mice, more than 4 x 10(4) m phi colony
      forming cells (M-CFCs) per mouse were recovered in the peritoneal lavage fluid 5
      days after TG injection. 89Sr-treated mice, on the other hand, had only 20% of
      those in the control mice. Splenectomized and 89Sr-treated (Spx/89Sr) mice showed
      further depletion of bone marrow cells and monocytes and, as expected, total
      numbers of peritoneal M-CFCs were severely depressed to less than 1% of those in
      the control mice. The results suggest that levels of peritoneal M-CFCs are
      strongly dependent on the presence of radiosensitive bone marrow cells and
      circulating monocytes, and resident peritoneal m phi s activated locally by
      inflammatory stimuli do not form m phi colonies under the defined conditions.

PMID- 1402391
TI  - Change in the frequency of apoptosis after low- and high-dose X-irradiation of
      human lymphocytes.
AB  - The purpose of the present study was to correlate the type and frequency of cell
      death in human lymphocytes receiving variable doses of X-irradiation. Monocyte
      depleted lymphocyte fractions were exposed in vitro to variable doses of X-rays
      of 0-20 Gy (0-2000 rads) and incubated for 4 and 16 h. An assessment of the mode
      of cell death (apoptosis vs. classical necrosis) was carefully evaluated using a
      multidisciplinary approach using light, fluorescence and electron microscopy
      (EM), and dye exclusion assays. Eosin Y exclusion assays indicated the absence of
      classical necrosis occurring in short-term cultures (4 h postirradiation). An
      assessment of cell counts, however, revealed a mean decrease of 4% at 0 Gy and
      13% at 10-20 Gy (1000-2000 rads). The predominant mode of cell death was
      apoptosis, but the percent apoptotic cells (determined by EM) did not parallel
      this increase in cell loss with increasing radiation and actually decreased at
      doses above 5 Gy (500 rads). The discrepancy between percent cell loss and
      percent apoptosis was explained by a proposed change in overall duration of the
      apoptotic process. In long-term cultures (16 h postirradiation), a combination of
      classical necrosis, classical apoptosis, and combined apoptosis and necrosis
      (secondary necrosis of apoptotic cells) was apparent and was associated with a
      marked decrease in viability. Irradiation effects on lymphocytes showing none of
      the morphologic features of apoptosis or classical necrosis in short-term culture
      were evidenced by an increase in nuclear lobation. The results of this study
      indicate that the vast majority of peripheral blood lymphocytes are
      radioresistant. The use of irradiation in an in vitro model to study the
      biochemical events of the apoptotic process is also evaluated.

PMID- 1402392
TI  - Tumor cell IL-6 gene expression is regulated by IL-1 alpha/beta and TNF alpha:
      proposed feedback mechanisms induced by the interaction of tumor cells and
      macrophages.
AB  - In the present report, we show that progressive growth of the immunogenic
      C57BL/6J sarcoma, MCA/76-9, was accompanied by an increase in serum interleukin-6
      (IL-6) activity. The possible pathways leading to the induction of IL-6 release
      by the tumor cells are described. It was shown that macrophage products IL-1
      alpha, IL-1 beta, and to a lesser extent, TNF alpha, induced the tumor cells in
      vitro to transcribe the IL-6 gene and release the gene product. IL-1 induced
      significantly more IL-6 mRNA and bioactivity than TNF alpha, although both
      cytokines induced a cumulative increase of bioactivity in the supernates over a
      period of 24 h. The tumor cells were shown to express receptors for IL-1 alpha,
      which could be blocked with anti-IL-1 receptor antibody. Given the previous
      reports that tumor-associated macrophages expressed both IL-1 alpha/beta and TNF
      alpha, the data suggest, first, that the mutual interaction of tumor cells and
      macrophages in situ may contribute to the observed increase in circulating IL-6
      activity, and second, that the release of IL-6 in vivo may serve to regulate both
      anti-tumor immune responses and suppressor mechanisms.

PMID- 1402394
TI  - Intracellular cholesterol transport.
AB  - The intracellular movement of cholesterol in mammalian cells may involve complex
      pathways by which the sterol moves to various cellular sites and mediates
      transcriptional regulation, enzyme activation, and protein degradation. Current
      evidence indicates that there are three distinct pathways modulating
      intracellular cholesterol trafficking. The movement of endogenously synthesized
      cholesterol from the endoplasmic reticulum appears to be distinct from movement
      of exogenous, low density lipoprotein (LDL)-derived cholesterol to the plasma
      membrane. In addition, steroidogenic cells possess a third mechanism by which
      cholesterol is transported to the mitochondria to initiate steroid hormone
      synthesis. In this review, we have outlined the current knowledge of cholesterol
      transport mechanisms and pathways and have described approaches that may help
      define cholesterol trafficking mechanisms in molecular detail. The use of genetic
      and molecular biologic techniques can potentially reveal gene products that are
      involved in intracellular cholesterol transport and regulation as well as those
      that may secondarily affect this process.

PMID- 1402393
TI  - A synthetic peptide homologous to retroviral envelope protein down-regulates TNF
      alpha and IFN-gamma mRNA expression.
AB  - We investigated the influence of CKS-17, a synthetic heptadecapeptide that
      corresponds to a highly conserved domain of the immunosuppressive retroviral
      envelope protein p15E, on staphylococcal enterotoxin B (SEB)-induced TNF-alpha
      gene expression in human peripheral blood mononuclear cells and highly purified
      human monocyte preparations, as well as the production of TNF-alpha protein,
      using human peripheral blood mononuclear cells. RNA hybridization studies show
      that CKS-17 inhibits SEB-induced TNF-alpha mRNA accumulation in human peripheral
      blood mononuclear cells and human monocytes. CKS-17 is also shown to be highly
      suppressive for SEB-induced production of TNF-alpha proteins. Similarly, CKS-17
      inhibits expression of SEB-induced IFN-gamma mRNA in human peripheral blood
      mononuclear cells. These results suggest that CKS-17 down-regulates both TNF
      alpha and IFN-gamma production at mRNA level.

PMID- 1402395
TI  - Saposins: structure, function, distribution, and molecular genetics.
AB  - Saposins A, B, C, and D are small heat-stable glycoproteins derived from a common
      precursor protein, prosaposin. These mature saposins, as well as prosaposin,
      activate several lysosomal hydrolases involved in the metabolism of various
      sphingolipids. All four saposins are structurally similar to one another
      including placement of six cysteines, a glycosylation site, and conserved
      prolines in identical positions. In spite of the structural similarities, the
      specificity and mode of activation of sphingolipid hydrolases differs among
      individual saposins. Saposins appear to be lysosomal proteins, exerting their
      action upon lysosomal hydrolases. Prosaposin is a 70 kDa glycoprotein containing
      four domains, one for each saposin, placed in tandem. Prosaposin is
      proteolytically processed to saposins A, B, C and D, apparently within lysosomes.
      However, prosaposin also exists as an integral membrane protein not destined for
      lysosomal entry and exists uncleaved in many biological fluids such as seminal
      plasma, human milk, and cerebrospinal fluid, where it appears to have a different
      function. The physiological significance of saposins is underlined by their
      accumulation in tissues of lysosomal storage disease patients and the occurrence
      of sphingolipidosis due to mutations in the prosaposin gene. This review presents
      an overview of the occurrence, structure and function of these saposin proteins.

PMID- 1402396
TI  - Different reactivities of high density lipoprotein2 subfractions with hepatic
      lipase.
AB  - Human high density lipoproteins2 (HDL2) consist of particles that contain both
      apolipoprotein (apo) A-I and apoA-II (A-I/A-II-HDL2) and others that contain apoA
      I but are devoid of apoA-II (A-I-HDL2). When postprandial lipemia is pronounced,
      a fraction of HDL2 is converted into HDL2-like particles. These HDL3 exhibit
      lower apoA-I/apoA-II ratios than the parent HDL2, suggesting preferential
      conversion of A-I/A-II-HDL2 into HDL3 (J. Clin. Invest. 1984. 74: 2017-2023).
      Triglyceride transfer from triglyceride-rich lipoproteins to HDL2 and subsequent
      lipolysis by hepatic lipase are thought to mediate the conversion of HDL2 into
      HDL3. To understand why A-I/A-II-HDL2 are preferentially converted into HDL3, we
      separated postprandial HDL2 into A-I-HDL2 and A-I/A-II-HDL2 species by
      immunoaffinity chromatography using a monoclonal antibody for apoA-II, and
      determined the ability of HDL2 species i) to participate in protein-mediated
      lipid transfer; and ii) to interact with hepatic lipase in vitro. Triglyceride
      transfer from/to triglyceride-rich lipoproteins was similar for the two HDL2
      species. In contrast, A-I/A-II-HDL2 were twice as effective as A-I-HDL2 in
      liberating hepatic lipase immobilized on HDL3-Sepharose. Lipolysis of
      triglycerides by hepatic lipase was 60% higher in postprandial A-I/A-II-HDL2 than
      in postprandial A-I-HDL2. Hydrolysis of phosphatidylcholine by hepatic lipase was
      threefold higher in A-II-containing HDL2 when compared with HDL2 devoid of apoA
      II. The different lipolytic rates in HDL2 subspecies correlated with the size
      reduction of substrate lipoproteins. Reconstitution of postprandial A-I-HDL2 with
      apoA-II enhanced the rate of lipolysis by hepatic lipase to that observed in A
      I/A-II-HDL2. We conclude that it is the interaction with hepatic lipase rather
      than the rate of triglyceride transfer that results in the preferred conversion
      of postprandial A-II-containing HDL2 into HDL3, and that apoA-II exerts a crucial
      role in this process.

PMID- 1402397
TI  - Influence of eicosapentaenoic acid (20:5, n-3) on secretion of lipoproteins in
      CaCo-2 cells.
AB  - CaCo-2 cells, grown on filter membranes, were used to study the effects of fatty
      acids on cellular metabolism of triacylglycerol and phospholipids. The rate of
      triacylglycerol secretion was enhanced more than 2-fold, from 1 to 2 weeks after
      reaching confluency, in the presence of 0.6 mM fatty acids. Triacylglycerol
      secretion and oxidation of oleic acid increased 2- and 9-fold, respectively, with
      this culture system, as compared to cells grown on conventional plastic dishes.
      Eicosapentaenoic acid (20:5 n-3), when compared to oleic acid, did not reduce
      formation of triacylglycerol or enhance phospholipid synthesis in CaCo-2 cells
      during short term (less than 24 h) experiments, when the cells resided on
      membranes, regardless of what type of radioisotopes were used as precursors in
      the incubation media. However, the n-3 fatty acid was preferentially incorporated
      into phosphatidylinositol, lysophosphatidylcholine, and sphingomyelin, as
      compared to oleic acid. The disappearance from the apical medium and cellular
      uptake of labeled eicosapentaenoic and oleic acid were similar during incubations
      up to 24 h, and the metabolism of these fatty acids to acid-soluble materials and
      CO2 was equal. Light scattering analysis indicated that secreted lipoproteins of
      density less than 1.006 g/ml were in the same size-range as chylomicrons derived
      from human plasma. Assessment of secreted apolipoprotein B showed that by
      incubating CaCo-2 cells with oleic acid, apolipoprotein B levels increased
      approximately 1.4-fold when compared to cells incubated with eicosapentaenoic
      acid, whereas the amount of triacylglycerol and size-range of particles were
      similar for the two fatty acids. Our data indicate that CaCo-2 cells grown on
      filter membranes exhibit enterocyte-like characteristics with the ability to
      synthesize and secrete chylomicrons. Eicosapentaenoic acid and oleic acid are
      absorbed, metabolized, and influence secretion of lipoprotein particles in a
      similar way, except for some differences in incorporation of the fatty acids into
      certain phospholipid classes and a reduced secretion of apolipoprotein B. The
      culture conditions, including time after confluency and cellular support, are
      critical for the rate of secretion in the presence of eicosapentaenoic acid and
      oleic acid.

PMID- 1402398
TI  - Incorporation of dietary [14C]arachidonic acid and [3H]eicosapentaenoic acid into
      tissue lipids during absorption of a fish oil emulsion.
AB  - A preferential incorporation of dietary arachidonic acid (20:4, n-6) into chyle
      lipoprotein phospholipids, a relative resistance of 20:4 esters of chyle
      triacylglycerol (TG) to hydrolysis by lipoprotein lipase, a preferential
      utilization of 20:4 for phospholipid acylation, and a low rate of oxidation of
      20:4 are factors that may contribute to the differences seen in the incorporation
      into tissue lipids between absorbed 20:4 and the predominant dietary 16-18 carbon
      fatty acids. In this study we fed [14C]20:4 and [3H]eicosapentaenoic acid (20:5,
      n-3) as free fatty acids in a fish oil emulsion to rats and analyzed the
      radioactivity in different tissue lipids after 1, 2, and 4 h. The purpose was to
      examine the degree of similarity in the fate of the two major eicosanoid
      precursors during the absorption of a fish oil meal. The recovery after 2 and 4 h
      of 14C exceeded that of 3H in lipids of small intestine, serum, liver, heart,
      kidneys, and spleen. The differences increased with time, e.g., the liver
      contained 9.7 (+/- 0.7)% 3H and 17.9 (+/- 1.4)% of the 14C (P less than 0.001),
      and the upper half of the small intestine 10.0 (+/- 0.8)% of the 3H and 22.8 (+/-
      1.1)% of the 14C (P less than 0.001) after 4 h. The 14C and 3H radioactivity per
      g tissue after 4 h ranked as follows: liver and brown adipose tissue greater than
      kidneys greater than heart, lungs, spleen, and serum greater than colon greater
      than white adipose tissue and testes, the differences between tissues being up to
      50-fold. There were up to fourfold variations in the 14C/3H ratios between
      tissues after 4 h, the highest value being observed in the heart and the lowest
      in white adipose tissue. Of the radioactivity retained in liver and intestine,
      more 14C and 3H was in phospholipids and less in triacylglycerol (TG), the
      differences being largest in the liver, e.g., after 4 h 57.6 (+/- 0.8)% of the
      14C and 29.9 (+/- 0.9)% of the 3H (P less than 0.001) in the liver was in
      phosphatidylcholine (PC). In both intestine and liver the highest 14C/3H ratios
      were found in phosphatidylinositiol (PI). Also phosphatidylethanolamine (PE)
      contained more 14C than 3H but the quantitative differences were relatively small
      after 4 h. In heart the proportions of 3H and 14C found in PE and PI did not
      differ, whereas more of the 14C was in PC and more of the 3H was in cardiolipin
      and phosphatidylserine.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1402399
TI  - Effect of cutaneous permeability barrier disruption on HMG-CoA reductase, LDL
      receptor, and apolipoprotein E mRNA levels in the epidermis of hairless mice.
AB  - Disruption of the permeability barrier results in an increase in cholesterol
      synthesis in the epidermis. Inhibition of cholesterol synthesis impairs the
      repair and maintenance of barrier function. The increase in epidermal cholesterol
      synthesis after barrier disruption is due to an increase in the activity of
      epidermal HMG-CoA (3-hydroxy-3-methylglutaryl CoA) reductase. To determine the
      mechanism for this increase in enzyme activity, in the present study we have
      shown by Western blot analysis that there is a 1.5-fold increase in the mass of
      HMG-CoA reductase after acute disruption of the barrier with acetone. In a
      chronic model of barrier disruption, essential fatty acid deficiency, there is a
      3-fold increase in the mass of HMG-CoA reductase. Northern blot analysis
      demonstrated that after acute barrier disruption with acetone or tape-stripping,
      epidermal HMG-CoA reductase mRNA levels are increased. In essential fatty acid
      deficiency, epidermal HMG-CoA reductase mRNA levels are increased 3-fold. Thus,
      both acute and chronic barrier disruption result in increases in epidermal HMG
      CoA reductase mRNA levels which could account for the increase in HMG-CoA
      reductase mass and activity. Additionally, both acute and chronic barrier
      disruption increase the number of low density lipoprotein (LDL) receptors and LDL
      receptor mRNA levels in the epidermis. Moreover, epidermal apolipoprotein E mRNA
      levels are increased by both acute and chronic perturbations in the barrier.
      Increases in these proteins in response to barrier disruption may allow for
      increased lipid synthesis and transport between cells and facilitate barrier
      repair.

PMID- 1402400
TI  - Water-phase palmitate concentrations in equilibrium with albumin-bound palmitate
      in a biological system.
AB  - The palmitate (PA) binding and transport capacity of human and bovine red cell
      membranes enables us to establish, in a biological system, the existence of a
      well-defined monomer concentration in equilibrium with PA bound to bovine serum
      albumin (BSA, 30 microM) inside the resealed red cell ghosts. Supernatants of
      suspensions of the [3H]PA-labeled ghosts contain a tiny quantity of dissolved
      binding capacities besides the monomer PA. This is demonstrated by linear
      regression of supernatant tracer concentrations versus ghost concentrations in a
      dilution series. The extrapolated value, corresponding to zero ghost
      concentration, is the monomer PA concentration in equilibrium with PA bound to
      BSA within the ghosts in molar ratio (nu). Measurements have been carried out for
      nu between 0.1 and 1.5 and at 0 degrees C, 10 degrees C, 23 degrees C and 38
      degrees C. The important nu-dependent binding of PA to the ghost membrane itself
      enables us to use preparations of BSA-free ghosts in the same way, whereas this
      is impossible in the case of arachidonic acid. Within the physiological range of
      nu the PA monomer concentrations are accounted for by an apparent dissociation
      equilibrium constant (Kd) 3.4 10(-8) M at 38 degrees C calculated on basis of
      three equivalent binding sites per mol BSA. Kd depends on temperature with a well
      defined enthalpy of 38.4 kJ/mol.

PMID- 1402401
TI  - Retention of glucose by N-linked oligosaccharide chains impedes expression of
      lipoprotein lipase activity: effect of castanospermine.
AB  - The effect of castanospermine (CSTP), an inhibitor of glucosidase I, on
      processing, activity, and secretion of lipoprotein lipase was studied in 3T3-L1
      adipocytes. Processing was analyzed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) of endoglycosidase H (endo H)-digested subunits of
      lipoprotein lipase from cells incubated 1-2 h with [35S]methionine. Lipoprotein
      lipase in untreated cells consisted of two groups of subunits, M(r) = 55,000
      58,000 and M(r) = 53,000-55,000. The heavier subunits were endo H-resistant,
      whereas the others were either totally or partially endo H-sensitive. The lipase
      secreted by untreated cells contained primarily endo H-resistant subunits.
      Immunofluorescent studies showed that lipoprotein lipase accumulated in Golgi in
      untreated cells. CSTP, 100 micrograms/ml for 18 h, decreased intracellular lipase
      activity by 80% and decreased secretion of lipase activity by 91%. Most of the
      lipase subunits in CSTP-treated cells were totally endo H-sensitive with M(r) =
      57,000, some were partially endo H-sensitive, and a trace was endo-H resistant.
      Totally endo H-sensitive subunits in CSTP-treated cells had a M(r) 2,000-4,000
      larger than that in untreated cells, indicating impaired trimming of sugar
      residues from oligosaccharide chains of the lipase in CSTP-treated cells. The
      small amount of lipase secreted by CSTP-treated cells consisted primarily of
      partially endo H-sensitive subunits, with one sensitive and one resistant chain
      per subunit. Immunofluorescent studies showed that lipoprotein lipase was
      excluded from Golgi in CSTP-treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402402
TI  - Characteristic distribution of glycolipids in gadoid fish nerve tissues and its
      bearing on phylogeny.
AB  - Glycolipids were isolated from nerve tissues of gadoid fishes including Alaskan
      pollack and Pacific cod. Their chemical structures were determined by gas-liquid
      chromatography and gas chromatography-mass spectrometry, and their constituents
      were analyzed in detail and compared with those of glycolipids from other fish
      groups. The results revealed that gadoid fish nerve membranes contain peculiar
      glycolipid molecular species that are distinctly different from those in other
      teleostean fishes and higher vertebrates. The mole percentage ratio of the four
      major glycolipids (cerebroside-sulfatide-galactosylglyceride-sulfogalactosylglyce
      ride) was 48:12:25:15, indicating profound accumulation of glycoglycerolipids.
      Galactosylglyceride and sulfogalactosylglyceride were primarily of the diacyl
      type (greater than 90%), the major fatty acids being 16:0 and 18:1. An abundance
      of glucocerebroside (25 to 55% of cerebroside) and its fatty acid ester (37 to
      47% of ester cerebroside) was noted. Cerebroside and sulfatide were characterized
      by the absence of hydroxy and odd numbered fatty acids, and 24:1 acid was a
      predominant component of both glucocerebroside and galactocerebroside.
      Subcellular fractionation revealed that myelin membranes comprised such unusual
      glycolipid constituents as those seen in whole nerve tissues. A vertebrate whose
      nerve membranes consist of such peculiar glycolipid molecules has not previously
      been reported. The characteristics of the glycolipid composition in gadoid fishes
      are discussed in relation to myelin functions, physicochemical properties of
      nerve membranes, and the phylogenic significance of this fish group.

PMID- 1402403
TI  - Cholesterol absorption and synthesis related to low density lipoprotein
      metabolism during varying cholesterol intake in men with different apoE
      phenotypes.
AB  - The aim of the present study was, first, to investigate whether cholesterol (C)
      absorption, enhanced by cholesterol feeding, was related to synthesis of
      cholesterol, serum level of low density lipoprotein (LDL)-C, and receptor
      activity for LDL apolipoprotein (apo) B in healthy men. Secondly, we were
      interested in whether apolipoprotein E (apoE) phenotypes contributed to
      cholesterol and LDL apoB metabolism under these conditions. We studied 29 home
      living men aged 55 +/- 1 (mean +/- SE) years on a low-fat, low cholesterol (208
      +/- 13 mg/day) diet followed by a low-fat high cholesterol (878 +/- 38 mg/day)
      diet during 5 weeks. Cholesterol feeding increased total cholesterol, LDL-C, high
      density lipoprotein (HDL)-C, and LDL apoB levels from 10% to 13% (P less than
      0.05) and bile acid production and cholesterol turnover by 16% (P less than
      0.05), decreased the fractional catabolic rate (FCR) for LDL apoB by 10% (P less
      than 0.05) and cholesterol absorption efficiency by 8% (P less than 0.05), while
      cholesterol synthesis only tended to decrease. During the cholesterol feeding,
      LDL-C was positively related to apoB production rate and cholesterol absorption
      efficiency (P less than 0.05), and negatively related to bile acid and
      cholesterol synthesis (P less than 0.05) and FCR for LDL apoB, which, in turn,
      was negatively related to cholesterol absorption efficiency and positively to
      bile acid synthesis. ApoE phenotype was positively related to TC, LDL-C, and LDL
      apoB levels and negatively to FCR for LDL apoB. The increase of the LDL-C level
      by the high cholesterol intake was positively correlated with LDL-C on high
      cholesterol diet and apoE phenotypes, so that the increase was 7% in apoE2 (ns),
      11% in apoE3 (P less than 0.05), and 18% in apoE4 (P less than 0.05); the
      increase of bile acid synthesis was significant only in subjects with apoE2.
      Moreover, the increase of LDL-C was positively related to the absolute amount of
      dietary cholesterol absorbed and negatively to FCR for LDL apoB. The findings
      suggest that the higher the LDL-C level, the higher is the absorption efficiency
      of cholesterol and production of LDL apoB, and the lower is the removal of LDL
      apoB and synthesis of both bile acids and cholesterol, and the more frequently
      the subjects had epsilon 4 allele. The nonresponsiveness to dietary cholesterol
      was dependent on low LDL-C level, apoE2 phenotype, and effective bile acid
      synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1402404
TI  - Effect of phospholipid fatty acid composition of endothelial cells on cholesterol
      efflux rates.
AB  - Human endothelial cells (EA.hy 926 line) were loaded with cationized low density
      lipoprotein (LDL) and subsequently incubated with fatty acid/bovine serum albumin
      complexes. The fatty acids were palmitic, oleic, linoleic, arachidonic, and
      eicosapentaenoic acids. The preincubations resulted in extensively modified fatty
      acid profiles in cell membrane phospholipids and in cellular cholesteryl esters.
      The cholesterol efflux from these fatty acid-modified cells was measured using
      0.2 mg high density lipoprotein3 (HDL3)/ml medium. The efflux was significantly
      higher for the palmitic acid-treated cells, compared to all other fatty acid
      treatments. These differences in efflux rates were not caused by changes in the
      binding of HDL3 to high affinity receptors on the EA.hy 926 cells. Efflux
      mediated by dimethyl suberimidate-treated HDL3, which does not interact with high
      affinity HDL receptors, was similar to efflux induced by native HDL3 after all
      fatty acid treatments. Our results indicate that high affinity HDL receptors are
      not important for HDL-mediated efflux of cell cholesterol. The fatty acid
      composition of the cell membrane phospholipids may be an important determinant.

PMID- 1402405
TI  - Enterohepatic circulation in hamsters with an extracorporeal bile duct.
AB  - The present study describes a novel technique for investigations of the
      enterohepatic circulation in the hamster with an extracorporeal bile duct that
      allows long-term bile collection in the free-moving animal. The animals recovered
      for 7 days after the operation before the external loop was cut and bile was
      collected over a period of 78 h. Under these optimal conditions, initial bile
      flow (651 +/- 89 microliters per 100 g.h-1) and the secretion rates of biliary
      lipids were several-fold higher than reported in an earlier study using the acute
      fistula hamster. Biliary cholesterol secretion amounted to 369 +/- 32 nmol per
      100 g.h-1, phospholipid secretion was 2.6 +/- 0.3 mumol per 100 g.h-1, and total
      bile acid secretion was 31.9 +/- 2.2 mumol per 100 g.h-1. A clearcut diurnal
      rhythm was demonstrated for bile flow and all biliary constituents. After 9 h the
      depletion of the bile acid pool was complete and cholic acid synthesis
      derepressed 1.4-fold from a basal rate of 818 nmol per 100 g.h-1, whereas the
      derepression of chenodeoxycholic acid synthesis was even less pronounced. Biliary
      cholesterol output increased 2.2-fold, but the phospholipid secretion was
      constant during the full experiment. It may be concluded that the technique of an
      extracorporeal bile duct in the free-moving animal allows studies of bile
      secretion under optimal conditions. Most likely the bile secretion rates given
      above approach the physiological rates in the hamster.

PMID- 1402406
TI  - Determination of free and amidated bile acids by high-performance liquid
      chromatography with evaporative light-scattering mass detection.
AB  - A simple reverse phase high-performance liquid chromatographic method for a
      simultaneous analysis of free, glycine- and taurine-amidated bile acids is
      described. The resolution of ursodeoxycholic, cholic, chenodeocycholic,
      deoxycholic, and lithocholic acids, either free or amidated with glycine and
      taurine, is achieved using a C-18 octadecylsilane column (30 cm length, 4 micron
      particle size) with a gradient elution of aqueous methanol (65----75%) containing
      15 mM ammonium acetate, pH 5.40, at 37 degrees C. The separated bile acids are
      detected with a new evaporative light-scattering mass detector and by absorbance
      at 200 nm. A complete resolution of the 16 bile acids, including the internal
      standard nor-deoxycholic acid, is obtained within 55 min. Using the light
      scattering mass detector, amidated bile acids and, for the first time, free bile
      acids can be detected with similar detection limits in the order of 2-7 nmol. The
      new detector improves the baseline and the signal-to-noise ratio over the UV
      detection as it is not affected by impurities present in the samples with higher
      molar absorptivity than bile acids or by the change in the mobile phase
      composition during the gradient. The method fulfills all the standard
      requirements of precision and accuracy and the linearity of the mass detector is
      over 5 decade the detection limit. The new method has been used for the direct
      analysis of bile acid in stools and bile with only a preliminary clean-up
      procedure using a C-18 reverse phase extraction.

PMID- 1402407
TI  - Capillary gas-liquid chromatographic separation of bile alcohols.
AB  - Gas-liquid chromatographic separation of C23, C24, C25, C26, and C27 bile
      alcohols with either 3 alpha, 7 alpha-dihydroxylated or 3 alpha, 7 alpha, 12
      alpha-trihydroxylated ring system on two capillary columns, CP-Sil-19 CB and CP
      Sil-5 CB, is described. Bile alcohols with two ring hydroxyl groups at 3 alpha-
      and 7 alpha-positions consistently showed larger retention times on CP-Sil-19 CB
      columns and smaller retention times on CP-Sil-5 CB columns than the corresponding
      bile alcohols with three ring hydroxyl groups at 3 alpha-, 7 alpha-, and 12 alpha
      positions. Resolutions of all bile alcohols were better on CP-Sil-19 CB columns;
      however, we hope that the gas-liquid chromatographic characteristics on the two
      columns will be useful for better identification of bile alcohols in biological
      fluids.

PMID- 1402408
TI  - The efficacy of chiropractic manipulation for back pain: blinded review of
      relevant randomized clinical trials.
AB  - OBJECTIVE: To assess the efficacy of chiropractic for patients with back pain.
      DATA SOURCES: Randomized clinical trials (RCTs) on spinal manipulation were
      identified with a Medline search (1966-1990), by citration tracking, and by
      manual examination of the relevant chiropractic reference systems [Chiropractic
      Research Archives Collection and Index to Chiropractic Literature]. [Indexing
      terms, Medline; backache, musculoskeletal diseases, manipulation, osteopathy or
      chiropractic in combination with evaluation studies, outcome and process
      assessment, prospective studies, comparative studies, clinical trials or double
      blind method. Indexing terms, Chiropractic Research Archives Collection: backache
      therapy-chiropractic clinical trials, cost benefit analysis, evaluation studies-
      chiropractic, manipulation--spinal, prospective studies, sciatica-therapy.
      Indexing terms, Index to Chiropractic Literature, backache therapy, clinical
      trials, cost benefit analysis, intervertebral disc displacement-therapy.] STUDY
      SELECTION: All RCTs involving chiropractors as therapists. To find additional
      evidence from nonchiropractic RCTs, chiropractic standards similar to the type of
      treatment used in nonchiropractic trials were determined by a panel of blinded
      chiropractors. DATA EXTRACTION: Review by two blinded reviewers independently,
      using a list of methodological criteria, each of which was attached to a weight.
      The maximum was set at 100 points. DATA SYNTHESIS: We identified five
      chiropractic RCTs. No similarity to chiropractic standards could be detected in
      any of the nonchiropractic RCTs. No chiropractic RCT had a methodological score
      of more than 50 points. The authors of four of the trials report favorable
      results for chiropractic, while one refrains from drawing conclusions. The
      results of the chiropractic RCTs differed on the timing of maximal effect as well
      as on the subgroups showing the best treatment results. CONCLUSIONS: Although the
      small number of chiropractic RCTs and the poor general methodological quality
      precludes the drawing of strong conclusions, chiropractic seems to be an
      effective treatment of back pain. However, more studies with a better research
      methodology are clearly still needed.

PMID- 1402409
TI  - The effect of manipulation on pain and range of motion in the cervical spine: a
      pilot study.
AB  - OBJECTIVE: The objective of this pilot study was to determine the number of
      patients required for a randomized controlled trial of spinal manipulation for
      neck pain and to determine if there is a relationship between pain and range of
      motion (ROM) in the cervical spine. DESIGN: Fifty consecutive outpatients were
      studied in a pretest-posttest design without long-term follow-up. SETTING: The
      patients were taken from a primary cae outpatient teaching clinic specializing in
      back pain. PATIENTS: All patients had unilateral neck pain without neurological
      deficit. The patients were selected as a consecutive sample. INTERVENTION: All
      the patients received a single cervical manipulation. MAIN OUTCOME MEASURES:
      Prior to and immediately after the treatment, cervical ROM was recorded on a
      goniometer, and pain intensity was rated on the 101-point numerical rating scale.
      RESULTS: The results show an increase in all planes of post-treatment ROM and a
      decrease in post-treatment pain scores. Partial correlations between post
      treatment ROM and 101-point numerical rating scale scores reveal a significant
      relationship between a decrease in pain and an increase in cervical rotation (p <
      .005). CONCLUSIONS: Since the results of this pilot study are not controlled,
      they cannot be seen as proof supporting the clinical efficacy of manipulation for
      neck pain. However, the correlation between an increase in cervical rotation and
      a decrease in pain is clinically instructive. In addition, the outcome measures
      used in this study could prove to be useful in the design of future randomized
      controlled trials of cervical manipulation.

PMID- 1402410
TI  - Three-dimensional head kinematics and clinical outcome of patients with neck
      injury treated with spinal manipulative therapy: a pilot study.
AB  - OBJECTIVE: Finite helical axis parameters (FHAP) of the cervical spine and
      clinical measures were obtained to evaluate neck function and the clinical
      effects of spinal manipulative therapy in patients with "whiplash" (WL) type neck
      injury. DESIGN: Descriptive case series, 1 yr follow-up. SETTING: Three private
      chiropractic practices. SUBJECTS: Ten consecutive new patients with a history of
      neck injury, nine asymptomatic, volunteer controls. INTERVENTIONS: A 6-wk regimen
      of short lever manually assisted adjustments with an Activator Instrument, while
      acute, four patients received interferential electrotherapy. MAIN OUTCOME
      MEASURES: Cervical FHAP during normal movements, neck pain (visual analogue
      scale), active cervical range of motion and follow-up questionnaire. RESULTS:
      Based on six patients, the FHAPs appeared to mirror the clinical condition, being
      markedly deviant from the patterns observed in the control group for at least one
      or more of the tracking tasks for all but one of the patients. Mean pain scores
      decreased from 44.1 to 10.5 (t = 4.93; p < .0001) and mean total range of motion
      increased from 234 to 297 degrees (t = 5.68; p < .0001). At 1 yr, seven
      respondents noted stability of their symptoms at or near the level reported
      immediately after the 6-wk treatment period. CONCLUSIONS: Based on these
      preliminary data: a) FHAPs may aid in diagnosing and monitoring treatment of neck
      dysfunction, b) spinal manipulative therapy may be beneficial to some patients
      with neck injury and future study is warranted as a means to promote recovery of
      patients with neck injuries.

PMID- 1402411
TI  - The descriptive profile of low back pain patients of field practicing
      chiropractors contrasted with those treated in the clinics of west coast
      chiropractic colleges.
AB  - OBJECTIVE: To compare the demographic and clinical characteristics of low back
      pain patients from chiropractic college clinics and private practice settings on
      the west coast of the United States. DESIGN AND SETTING: A survey analysis of
      consecutive new patients in a specified time frame from multiple private office
      settings contrasted with a previous survey of consecutive new patients in a
      similar time frame from chiropractic college clinics. PATIENTS: In the private
      practice setting, new patients were selected on a consecutive basis as subjects
      for the study. Selection was limited to low back pain patients. INTERVENTIONS:
      None. This was a self-report survey only. MAIN OUTCOME: There is a strong
      similarity of the two low back pain patient groups, with the exception of higher
      levels of income, work time loss, severity and functional disability reported in
      the private practice setting. RESULTS: Similarities between the two low back pain
      patient groups were found in the distribution of gender, age, job description and
      education. Statistical significances were not determined due to variations in
      data collection. CONCLUSIONS: The two patient populations are reasonably
      comparable in sociodemographic variables, but clinical variation does exist.
      These results suggest the need to consider clinical findings when extrapolating
      research findings in a college clinic setting to the chiropractic profession in
      general.

PMID- 1402412
TI  - The reliability of lumbar motion palpation.
AB  - OBJECTIVE: This review surveys the literature regarding reliability studies of
      lumbar motion palpation. DATA SOURCES: Using the indexing terms motion palpation
      lumbar spine and palpation, the following English language databases were
      surveyed: a) Medline, including back file; b) Embase; c) Cinahl; and d) Epic.
      Additionally, a manual search of the Chiropractic Research Archives Collection
      and JMPT was performed and researchers at Western States Chiropractic College
      were consulted. Pertinent references cited in bibliographies of retrieved papers
      were included if contributory. STUDY SELECTION: Studies pertaining to intra- and
      interexaminer reliability of lumbar motion palpation were reviewed. DATA
      EXTRACTION: Statistical analysis, subject selection, method of palpation and
      sources of error are discussed. DATA SYNTHESIS: Multiple variations were noted in
      type of palpation, subjects examined, statistical analysis and experience of
      examiners. CONCLUSIONS: To date, most studies have demonstrated marginal to poor
      interexaminer reliability, while good to moderate intrarater reliability has
      generally been reported.

PMID- 1402413
TI  - Metastatic testicular seminoma of the cervicothoracic spine.
AB  - A case of metastatic testicular seminoma affecting the cervico-thoracic spine is
      reported along with its clinical and radiographic findings. Case progression is
      discussed.

PMID- 1402414
TI  - Chiropractic research: the ethics.

PMID- 1402415
TI  - Art, science and philosophy: enthusiasm and the untestable.

PMID- 1402416
TI  - Conservative management of an L4-L5 left nuclear disk prolapse with a
      sequestrated segment.

PMID- 1402417
TI  - Maximizing productivity of new associate physicians: proven strategies.

PMID- 1402419
TI  - The challenge: a generation of "growing healthy" children.

PMID- 1402418
TI  - Medical record documentation and the new visit codes.

PMID- 1402420
TI  - Family violence: a national epidemic.

PMID- 1402421
TI  - Teenage pregnancy: everyone's responsibility.

PMID- 1402422
TI  - Of hope and the world of diddly poo.

PMID- 1402423
TI  - Empowering the medical staff through their bylaws.

PMID- 1402424
TI  - Juggling fiduciary responsibility (Part 2): Are you saving too much for
      retirement?

PMID- 1402425
TI  - Medical staff bylaws: a contract or a meaningless mouthing of words?

PMID- 1402426
TI  - Getting paid for your hospital work.

PMID- 1402428
TI  - Peer review, hearing requirements, and antitrust: maximizing Federal Health Care
      Quality Improvement Act compliance and immunity.

PMID- 1402427
TI  - Physician contracts: HMOs, PPOs, and hospital-based physicians, exclusive
      contracts and employment.

PMID- 1402429
TI  - Market power, collusion, and exclusion in health care antitrust enforcement.

PMID- 1402430
TI  - Theology and bioethics: should religious traditions have a public voice?

PMID- 1402431
TI  - Religion, theology, church, and bioethics.
AB  - Modern medical ethics developed in America after mid-century chiefly at
      theological schools, but discourse on bioethics soon moved to the pluralist
      secular settings of the academy and the clinic, where it acquired a philosophical
      and intentionally non-religious cast. An effort was made, on the grounds of
      'liberal culture' and 'late Enlightenment rationality' to find a framework for
      inquiry which aspired to the universal. Today, while that language persists, it
      coexists with, challenges, and is challenged by forms of ethical analysis and
      advocacy which take into consideration the 'thickness' of complicating narrative
      and reasoning based in the many religious traditions. It has become incumbent
      upon advocates of those traditions to propose 'publicly accessible' argument.

PMID- 1402432
TI  - Humility in health care.
AB  - Humility, properly understood as a sense of one's limits, is one of the goods
      internal to the practice of health care. Humility in Christian tradition has both
      a relational aspect and an epistemological aspect. Each of these is evident in
      the practice of medicine. In its relational aspect, humility includes reverence
      or awe for the grace and strength of patients and their care-givers, a sense that
      the care-provider is not self-sufficient but needs the care-receiver, and
      recognition of the worth of those who are oppressed and outcast. In its
      epistemological aspect, humility is exhibited in respect for the meaning system
      of the patient and recognition of the limits of medical paradigms and their need
      for correction from the patient's perspective. The power wielded by the
      profession of medicine in contemporary society does not preclude the exercise of
      humility within the profession.

PMID- 1402433
TI  - Jewish theology and bioethics.
AB  - This article explores the theological foundations of both classical and
      contemporary Jewish ethics, with special reference to biomedical issues.
      Traditional views concerning God's revelation to Israel are shown to underlie the
      methodological orientation of classical Jewish ethics, which is both legalistic
      and particularistic. Contemporary Jewish ethicists, by contrast, have tended to
      embrace more liberal views of revelation which have mitigated both the legalism
      and the particularism of their approach. Apart from methodological
      considerations, much of the content of Jewish medical ethics has also been shaped
      by theological concerns. Specifically, a Jewish theology of creation provides
      basic norms and values which inform Jewish responses to a range of contemporary
      biomedical issues. Finally, it is suggested that the theological roots of this
      ethical tradition do not disqualify it from making a significant contribution to
      the wider discussion of biomedical issues in our secular, pluralistic society.

PMID- 1402434
TI  - Catholic 'natural law' and reproductive ethics.
AB  - Catholic natural law has had a long and evolving interest in bioethics. Thomas
      Aquinas left natural law a legacy of great flexibility in evaluating goods within
      a whole life. He also bequeathed to the Church the basis for an abolutism on
      sexual issues. Modern reproductive medicine and a deeper understanding of human
      freedom have reopened these issues. The Vatican has developed new, holistic
      arguments to proscribe reproductive interventions, but critics remain unconvinced
      that marital relationships and goods have been adequately evaluated. The
      resolution of this debate will require further experience and reflection.

PMID- 1402435
TI  - Policy arguments in a public church: Catholic social ethics and bioethics.
AB  - This paper is an analysis of the relationship of social ethics and bioethics in
      Roman Catholic theology. The argument of the paper is that the character of both
      Catholic moral theology and ecclesiology shape the broadly defined interest of
      the church in bioethics. The paper examines the common elements of social ethics
      and bioethics in Catholic teaching, describes how ecclesiology shapes Catholic
      public policy and uses the examples of abortion and health care to illustrate the
      relationship of Catholic social thought and bioethics. In developing the
      relationship of these two dimensions of Catholic moral argument the article
      highlights how the appeal to natural law categories differs in social ethics and
      bioethics and how the two topics are received differently in the theological
      community. It also seeks to illustrate how the premises of Catholic social ethics
      remain central to public positions taken on bioethics.

PMID- 1402436
TI  - A computer-based, automated, telephonic system to monitor patient progress in the
      home setting.
AB  - In this report we describe an automated, telephonic system to monitor the
      progress of patients convalescing at home. The system includes a computerized
      central station that is capable of automated voice communication over the
      telephone, using voice reproduction, and touch-tone recognition. Peripheral
      hardware in multiple monitored homes need include only a touch-tone telephone,
      but may also be augmented by inexpensive, rudimentary diagnostic aids, such as a
      scale for body weight, a thermometer, or a blood pressure cuff and manometer.
      Current central hardware includes a NeXT computer, a fax modem, and a specialized
      telecommunications modem developed specifically for voice telecommunication using
      the NeXT. The central station acts like a robotic nurse in that it asks patients
      a series of questions and records the responses. The subjective questions to be
      asked are patient individualized and pre-selected by the physician from a
      question menu including items targeted specifically for the patient's disease or
      condition. In addition, clinical data such as body weight, blood pressure, and
      body temperature obtained from in-home diagnostic aids may be transmitted to the
      central station over the telephone using touch tones. The time-of-day and
      frequency of calling are pre-selectable, according to the patient's preference
      and clinical status. Data obtained by the central station can be easily accessed
      by the duty nurse via menu driven software. Reports depicting significant
      responses as a function of time are generated in graphical format to facilitate
      rapid identification of adverse trends. Hard copy reports can be dispersed
      directly by fax. Results from a pilot study show patients with cardiac disease
      readily use the system without difficulty or complaints. In one patient a five
      pound increase in body weight was detected, which prompted the patient's
      cardiologist to adjust his medication. In this way automated telephone follow-up
      can provide early detection of complications before they become severe, making
      the home environment safer and more secure for convalescence and contributing to
      reduced health-care costs.

PMID- 1402437
TI  - Data management of an inflammatory bowel disease registry.
AB  - The history and etiology of inflammatory bowel disease which is characterized by
      two major disease processes: ulcerative colitis and Crohn's disease, remain
      unknown. Research is focussing on seven major areas of genetic, environmental and
      physiologic factors that apparently relate to this disease. Based on this
      background, a population based Inflammatory Bowel Disease Registry was
      established in 1987 in the Lehigh Valley area of southeastern Pennsylvania.
      Consent forms, patient data forms and protocols for operation and implementation
      were developed, and databases were designed to accommodate demographic, basic
      history, follow-up and relative history data. The databases were correlated with
      an IBD registry ID number which both enabled relational analyses and ensured
      confidentiality of data information. The registry continues to grow, providing
      feedback for both continued medical research and supportive information for IBD
      patients and their physicians.

PMID- 1402438
TI  - The Iowa Medical Information Network: a concept.
AB  - Iowa Methodist Medical Center (IMMC) was one of the nation's early developers of
      a "hospital/physician" system, entering the arena during October 1985, under the
      direction of Ginny Wagner. Their "MOLI-Link" system now serves over 150
      physicians in 50 locations, and is currently undergoing significant enhancement.
      MOLI-Link was originally developed using Annson Systems (IBAX) products, and has
      recently migrated to Wallace Computer Services (Wal-Link) software. Over the past
      4 years, IMMC has investigated wide-area medical information networking, and is
      now actively investigating development of the Iowa Medical Information Network.
      It is envisioned that IMIN would provide clinical, administrative, and
      educational information services throughout the IMMC 37 county referral area.

PMID- 1402439
TI  - CompreLink--a physician to physician communication network.
AB  - The Cleveland Clinic Foundation has developed a physician to physician
      communication network designed to meet the needs of their affiliate physicians-
      physicians who do not have admitting privileges at the Cleveland Clinic Hospital.
      This paper provides an overview of the CompreLink network as it exists today, as
      well as a glimpse into some of their plans for network expansion and development.

PMID- 1402440
TI  - Synapse Health Resources Online.
AB  - The University of Nebraska Medical Center maintains the Synapse Health
      Information Network to provide timely clinical and library resource information
      to health professionals across Nebraska and surrounding regions. The system is in
      over 115 sites across Nebraska and surrounding regions and maintains over 320
      network users.

PMID- 1402441
TI  - US HealthLink: a national information resource for health care professionals.
AB  - US HealthLink is a new, comprehensive online medical information system designed
      specifically for health care professionals. Available to individuals for a fixed
      fee, it includes literature, news, diagnostic decision support, drug
      interactions, electronic mail, and bulletin boards. It also provides user
      specific current awareness via clipping service, and fax delivery of both
      clipping and electronic mail information. US HealthLink can now be utilized to
      access a wide variety of medical information sources inexpensively.

PMID- 1402442
TI  - Two hundred and fifty patients with hemifacial spasm treated with botulinum toxin
      injection.
AB  - Two hundred and fifty patients with hemifacial spasm from the Movement Disorder
      Clinic, at Siriraj Hospital have been treated with botulinum toxin injection
      since January 1989 as a collaborating research project with Smith-Kettlewell Eye
      Research Institute in San Francisco. Each patient received 30 units in four
      injection sites over the hyperkinetic facial muscles. There were 169 female and
      81 male patients, the sex ratio of female to male was 2.1:1. The mean age of all
      patients was 50.2 +/- 12.6 years with the range of 22 to 78 years. The majority
      of patients had been suffering for 3-10 years. The results of botulinum toxin
      injection were classified as excellent in 81.2 per cent, moderate improvement
      10.0 per cent, mild improvement 6.8 per cent and no improvement or worse in 2.0
      per cent. There were complications of mild transient facial weakness in 44
      patients (17.6%) mild ptosis in 7 patients (2.8%) and excessive lacrimation in 1
      patient (0.4%). The effect of botulinum toxin treatment lasted for 3-6 months
      duration. Botulinum toxin injection is a simple and effective out-patient
      treatment for patients with hemifacial spasm with no systemic side effects and
      minor transient local complications.

PMID- 1402443
TI  - Spontaneous pneumothorax in chronic obstructive pulmonary disease.
AB  - There were 34 episodes of pneumothorax out of 400 episodes of COPD (i.e. 8.5% of
      the total) among patients who were admitted to Chulalongkorn Hospital during the
      period 1982 to 1986; the episodes of pneumothorax occurred among 22 males and one
      female, with the average age on admission being 64.0 +/- 8.5 years. All patients
      had a long history of smoking (average 40 years) with a history of recurrent
      pneumothorax (47.8%) and two episodes of pneumothorax per patient. Since only
      about one third of our patients had chest pain or positive signs of pneumothorax
      on physical examination, the possibility of pneumothorax should be considered in
      every patient who develops sudden and increasing shortness of breath, especially
      during mechanical ventilation, or even in association with other obvious
      precipitating factors, e.g. URI. With regard to complications, there were eight,
      four, two, two and five episodes of severe respiratory failure requiring assisted
      ventilation, tension pneumothorax, bilateral simultaneous pneumothorax,
      pneumomediastinum with subcutaneous emphysema, and plural effusion, respectively.
      The death rate was 23.5 per cent. Patients who had a pneumothorax requiring
      assisted ventilation or who developed a pneumothorax during assisted ventilation
      had a grave prognosis because of multiple complications from mechanical
      ventilation. Two episodes with minimal pneumothoraxes achieved re-expansion after
      conservative treatment. The treatment required 3.3 days for the lung to fully
      expand, 9.6 days when the air-leak stopped and the duration of tube drainage was
      10.8 days. Our study indicates that the longer the duration of lung collapse the
      longer the time required for re-expansion of the lung.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402444
TI  - Lipid disorders in Thai diabetic patients at Rajavithi Hospital.
AB  - Lipid abnormalities are common in diabetic patients. In this study, 71 per cent
      had hyperlipidemia. The incidence of combined hyperlipidemia,
      hypertriglyceridemia, and hypercholesterolemia were 29.5, 25.8 and 15.5 per cent
      respectively. Females were found to have higher cholesterol levels than males.
      Cholesterol and triglycerides levels were correlated with BMI and GHb but showed
      no correlation with age and duration of diabetes. HDL-C showed no correlation
      with BMI, GHb, age or duration of diabetes.

PMID- 1402445
TI  - The epidemiology of insulin-dependent diabetes mellitus (IDDM): report from
      Thailand.
AB  - The epidemiology of diabetes mellitus in Thai children aged 0-15 years was
      studied in 1985 and compared with a previous study done in 1984. Four hundred and
      seventy-six questionnaires were sent each year to hospitals in Thailand. In 1984,
      thirty-six cases of newly diagnosed diabetes mellitus were found of which 35 were
      IDDM and one was NIDDM. In 1985, twenty-seven cases of new IDDM were found, no
      case of NIDDM was reported. Two cases of MRD were reported from the Northeastern
      and Southern part of Thailand. The incidence of IDDM in the whole kingdom of
      Thailand was 0.19/100,000/year in 1984 and 0.14/100,000/year in 1985. The male to
      female ratio was 1:1.5 in 1984 and 1:2 in 1985. The peak age at diagnosis showed
      the main peak at 14 years old in boys. The peak age of girls preceded boys by 1-2
      years in 1984 and 1985. Similar findings in 1984 and 1985 were the onset of
      symptoms showing a seasonal variation with highest frequency in winter with a
      slight change of increased incidence in the rainy season of 1985. There was an
      increased incidence of IDDM in families with lower educational and socioeconomic
      levels. The newly diagnosed IDDM with DKA was 16.2, and 19.5 per cent in 1984 and
      1985. The incidence of IDDM in Thai children, aged 0-15 years seems to be the
      lowest compared to other countries previously described which might be due to
      some genetic and environmental including diet, micronutrient, eating habits and
      life-style which might play a role in the difference.

PMID- 1402446
TI  - The failure of a preprinted order form to alter physicians' antimicrobial
      prescribing pattern.
AB  - Use of antimicrobial agents is highly effective in reduction of morbidity and
      mortality due to infectious disease. There is, however, evidence that the use of
      such agents is frequently inappropriate worldwide. Several methods were tried to
      rationalize the use, and, among these, the preprinted order form (P.O.F.) offered
      the simplest and most efficient way. We studied the use of the P.O.F. in Siriraj
      Hospital, Bangkok Thailand, where there was overuse of antimicrobial agents using
      a historical-controlled intervention study. In period I (no P.O.F.), the
      antimicrobial overuse was 35 per cent, and this was not reduced by using the
      P.O.F. in period II (32%), which was one year apart. There was no difference in
      overuse after adjustment for differences in base-line characteristics which were
      thought to affect antimicrobial prescriptions i.e. physicians' workload,
      physicians' knowledge and the method of diagnosis of infectious disease. Reasons
      for failure of the P.O.F. in unclear. Misdiagnosis was unlikely since the correct
      diagnosis as revised by attending physicians and specialists was as high as 83
      per cent. The fear of malpractice suits was also not the reason because defensive
      medicine is not a problem in Thailand. The nature of the diseases, which lower
      the threshold to treat, the clinical immaturity and other unknown factors were
      thought to play a part in deviation from responsibility to perform according to
      written-justification.

PMID- 1402448
TI  - Liquid meal emptying in non-ulcer dyspepsia: a study in 22 Thai patients.
AB  - Twenty-four patients with non-ulcer dyspepsia (NUD) were recruited for gastric
      emptying study of liquid meal before and after 1 week's treatment with
      domperidone (80 mg in 19, 40 mg in 2, dropout 1 and excluded 2). Delayed gastric
      emptying was found in 8 of 22 (36.36%). Clinical improvement was found in 11
      patients after treatment. Gastric emptying improvement was found in 3 patients (2
      without clinical improvement). No correlation was found between the clinical and
      gastric emptying improvement. (Fisher exact test p greater than 0.25). Impaired
      liquid emptying is common in NUD and domperidone improved clinical symptoms in 50
      per cent of NUD in this study.

PMID- 1402447
TI  - Prevalence and intensity of Opisthorchis viverrini in rural community near the
      Mekong River on the Thai-Laos border in northeast Thailand.
AB  - The prevalence and intensity of Opisthorchis viverrini in fourteen villages in
      Nakhon-Phanom province, Northeast, Thailand have been investigated. Overall
      prevalence of O. viverrini infection was 66.4 per cent in a total population of
      2,412 individuals. The prevalence was 18.5 per cent in children under 5 years,
      38.9 per cent in those aged 5-9 years, and ranged from 64.9 per cent to 82.2 per
      cent in the age group above 10 years. The intensity of O. viverrini infection
      increased with age. The mean faecal egg output was highest in the 30-34 year age
      group and remained relatively constant through older ages. In all age groups the
      prevalence and intensity of infection in both men and women were similar. The
      population was divided according to the presence and intensity of infection as
      follow, 33 per cent were uninfected, 59 per cent had light infections (less than
      1,000 eggs per g of faeces; EPG), 7 per cent had moderate infections (1,000
      10,000 EPG), and 1 per cent had heavy (greater than 10,000 EPG). Other important
      intestinal infections found in this community are hookworm, Taenia spp. and
      Trichuris trichiura with the prevalence of 17.9 per cent, 1.1 per cent and 1.1
      per cent respectively.

PMID- 1402449
TI  - Compartmental change after weight reduction in childhood obesity.
AB  - Ten obese children aged 8-13 years participated in a 4-week program of weight
      reduction. Dietary restriction of 800 kcal/day and mild exercise were the two
      features of the program. With this regimen the investigators expected that their
      lean body mass would be preserved while body fat would decrease. After the 4-week
      program, we found that those who were mildly and moderately obese lost more than
      5 per cent of their body fat but less than 1 per cent of lean body mass. Those
      children with morbid obesity lost more than 5 per cent of body fat and lean body
      mass. It is concluded that the regimen is suitable for mild and moderate obesity,
      but for morbid obesity, a new regimen with higher energy and higher protein in
      the diet may be more suitable than the current one.

PMID- 1402450
TI  - Human pythiosis in Srinagarind Hospital: one year's experience.
AB  - We have reported four cases of human pythiosis arteritis from Srinagarind
      Hospital, Khon Kaen, Thailand. This unusual human infection occurring perhaps
      exclusively in thalassemia and hemoglobinopathy patients, should be noted by
      physicians, who work in areas with a high incidence of hemoglobinopathy, and for
      patients who present with unexplained arterial insufficiency. As our reported
      cases occurred within only one year, this condition may be more common than
      originally suspected and found more frequently if actively searched for.

PMID- 1402452
TI  - Problems in surgical treatment of congenital clubfoot.
AB  - Twenty-three patients with 32 congenital rigid clubfeet treated by posteromedial
      release were reviewed after a follow-up averaging 33 months. The feet were
      assessed both clinically and radiologically; a satisfactory result was obtained
      in 17 feet inspite of residual deformity of forefoot adduction. Early operation
      and adequate postoperative immobilisation were major factors in contributing to a
      satisfactory result.

PMID- 1402451
TI  - Eales' disease with myelopathy.
AB  - The first Thai case of Eales' disease with myelopathy is reported. This entity
      must be differentiated from other causes of myelopathy such as those due to
      infectious-inflammatory causes. The ophthalmologic findings are the most
      important diagnostic clues. Since many infectious diseases such as tuberculosis
      and dental sepsis may be potentially related to Eales' disease, and these
      infections are rather common in Thailand, the diagnosis of Eales' disease with
      neurological complications especially myelopathy should be looked for.

PMID- 1402453
TI  - Limb salvage for extremity sarcoma in Ramathibodi Hospital.
AB  - From May 1986 to July 1991, a retrospective review of 27 patients treated with
      limb salvage surgery for extremity sarcomas, was evaluated by our team. There
      were 12 males and 15 females with a mean age of 22.7 years (ranging from, 9 to 53
      years). The mean of the follow-up period was 27.6 months. (ranging from 6 to 62
      months). Twenty-four patients had bone sarcomas which included 20 osteosarcomas,
      3 chondrosarcomas and one adamantinoma. The locations of bone sarcomas were the
      proximal tibia (6 cases), distal femur (5 cases), proximal humerus (4 cases),
      proximal fibula (3 cases), scapula (3 cases), proximal femur (1 case), tibial
      shaft (1 case) and pelvis (1 case). The remaining three patients had malignant
      fibrous histiocytomas located in scapular, tibialis anterior muscle, and knee
      regions. In total there were 1 stage IA, 2 stage Ib, 1 stage IIA and 23 stage
      IIB. Twenty-four cases had wide excisions; two had marginal excisions and one
      radical excision. There were 17 bone reconstructions consisting of 11 allografts
      and 6 autografts. At the most recent follow-up examination, 74 per cent of the
      patients are alive and the overall disease free survival was 63 per cent. Local
      recurrences occurred in 11 per cent. The major complication rate was 3 per cent
      and the minor complication rate was 33 per cent. With respect to a functional
      outcome, 84 per cent of the patients achieved excellent or good results.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1402454
TI  - Chondrodysplasia punctata: a case report.
AB  - Chondrodysplasia Punctata is a rare condition in which there are numerous
      punctate areas of calcification in the epiphysis. The disease involves not only
      skeletal but also the cardiovascular, cutaneous, ocular and central nervous
      system. We present a newborn case with clinical as well as radiographic findings
      similar to Chondrodysplasia Punctata.

PMID- 1402455
TI  - Malignant osteoblastoma versus osteosarcoma: a case report.
AB  - A 33-year-old male developed a slow-growing mass at the anterior aspect of the
      left tibia for 8 months. The radiologic finding revealed a well-circumscribed
      osteolytic mass and appeared benign to most radiologists. The lesion was then
      excised locally. The histology revealed bizarre osteoblasts and osteoclast-like
      giant cells interspersing in the vascularized stroma and trabeculated osteoids;
      the periphery of the lesion showed sclerotic mature bones. Malignant
      osteoblastoma was, therefore, entertained and the patient was treated as such
      without aggressive surgery and chemotherapy. He has survived for 11 years.
      However, the diagnosis of malignant osteoblastoma was still a contradiction
      because of the presence of cartilage foci.

PMID- 1402456
TI  - Metastatic bone tumors in Ramathibodi Hospital, Thailand during 1985-90.
AB  - The study was aimed to analyse the histologic typings of metastatic bone tumors,
      age of patients and skeletal distributions in Ramathibodi Hospital. There were
      122 cases of metastatic bone tumors out of 217 cases of all malignant bone tumors
      as retrieved from the files of surgical records in the Department of Pathology,
      Ramathibodi Hospital from 1985 to 1990. Approximately 80 per cent of metastatic
      bone tumors were carcinomas of which adenocarcinoma was the most common and
      accounted for 44.3 per cent of all metastatic bone tumors. The most common site
      of biopsy which possibly reflects the skeletal distribution of metastases was the
      vertebra which accounted for 35 per cent. The average age of patients presenting
      with metastatic carcinomas was about 50 years which was comparable to those of
      other series. It was obvious that biopsy of metastatic lesions was helpful in
      narrowing the scope of investigation but could hardly define the primary sites
      without further investigations.

PMID- 1402457
TI  - Paget's disease of bone--clinico-pathology study of the first case report in
      Thailand.
AB  - Paget's disease of the bone is rare in Asia. We report a case of Paget's disease
      with clinico-pathology study and it appears to be the first case in Thailand. The
      case was a 44-year-old female of Chinese descent who developed pain in the left
      hip and sacral area for one year prior to admission to Vachira Hospital. The
      earlier clinical diagnoses were either osteoporosis or metastatic tumor. Biopsy
      of the right iliac bone was typical for Paget's disease of the bone.

PMID- 1402458
TI  - Soft tissue tumors in Ramathibodi Hospital: study of 1,682 cases during 1977
      1986.
AB  - A series of 1,682 cases in the service of the Department of Pathology,
      Ramathibodi Hospital from 1977 to 1986 was studied and classified according to
      WHO histologic typing of soft tissue tumors. The findings revealed that the three
      most common benign soft tissue tumors were lipoma (50.6%), vascular tumors
      (17.4%) and neurofibroma (7.3%), whereas, the three most common malignant soft
      tissue tumors were unclassified sarcoma (16.5%), rhabdomyosarcoma (15.5%) and
      neurofibrosarcoma (10.7%). Lipoma occurred at any age group with a mean age of 40
      years and affected males and females equally and common sites of involvement were
      neck (19.7%), back (19.7%) and upper arm (18.4%). Unclassified sarcoma was the
      most common among the malignant group accounting for 16.5 per cent of the total
      malignant soft tissue tumors. The age ranged from 7 to 70 years with a mean age
      of 27.4 years. The most common sites of involvement were the extremities (50%)
      especially the thigh.

PMID- 1402459
TI  - Urinary vanilmandelic acid determination using column chromatography.
AB  - A simple method for determination of urinary vanilmandelic acid, VMA, using
      column chromatography was described. The interfering substances in the urine were
      eliminated by passing the urine through a Dowex-1 x 2, 50-100 mesh, column and
      washing the column with distilled water. The VMA was eluted from the resin using
      K2CO3-containing 3.0 mol/l NaCl solution and determined spectrophotometrically
      after periodate oxidation reaction. This method yielded a standard curve which
      was linear up to 50 mg/l. The recoveries of the method as determined by addition
      technique ranged from 92.1 to 100.4 per cent with an average of 97.3 per cent.
      The method yielded satisfactory precisions with the coefficients of variation
      (C.V.) of less than 5.50 and 6.95 per cent for within-run and between-run
      experiments respectively. The method was sensitive to the concentrations of 1.2
      mg/l with recovery of 92.5 per cent and 2.6 mg/l with the recovery of 109.9 per
      cent for the standard and urinary VMA respectively. No interfering effects were
      found from epinephrine and norepinephrine (up to 2,000 micrograms/l),
      acetylsalicylic acid (up to 50 mg/l) and homovanillic acid (up to 10 mg/l) added
      to the pooled urine. The correlation coefficients (r) of 0.909 (n = 100) and
      0.905 (n = 100) were obtained when the urinary VMA values determined by the
      proposed and Pisano's methods and expressed as mg/l and mg/g creatinine were
      compared respectively. The column could be reused at least 5 times. The technique
      is suitable for any routine clinical laboratory.

PMID- 1402460
TI  - Morphological variation in pathogenic strains of Penicillium marneffei.
AB  - Penicillium marneffei is a dimorphic fungus known to be pathogenic to animals and
      man. The natural reservoir of this organism was known to be bamboo rats found in
      South Vietnam, Thailand and China. The first two human infections were reported
      in 1959 and 1973 from the United States. Up to 1984, five new cases of human
      penicillosis were reported from Thailand. Since then several more cases have been
      reported from different parts of the world mainly from the southern part of
      China. However, there are very limited mycological descriptions of this fungi. In
      this report, five Thai strains were studied for colonial morphology in comparison
      with Reference strain PLM 689. Variation in mycelial pigment was observed ranging
      from yellowish-green to orange with water soluble red pigment produced in every
      strain which can be seen early from the reverse side. Ultrastructural study by
      both scanning electron microscopy (SEM) and transmission electron microscopy
      (TEM) was compared with that of the reference strain PLM 689. PLM 689 strain had
      only biverticillate penicilli, but all five strains from Thailand had both
      monoverticillate and biverticillate penicilli which occasionally appeared on the
      same branch. The conidia of the Thai isolates were oval in shape and 1.3-2 x 0.7
      1.6 microns in size smaller than those of PLM 689 which were 2.5-4 x 2-3 microns.
      Phialides were also smaller and a little shorter but the number of phialides was
      similar to those of PLM 689 ranging 4-10 except for one strain which had 3-16
      phialides. All Thai strains have stipes smaller and somewhat longer than those of
      PLM 689.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402461
TI  - Microscopic examination of Cryptosporidium oocysts in diarrhoeal stools.
AB  - Unconventional microscopic means for investigation of Cryptosporidium oocysts in
      patients' stools were explored in an attempt to obtain a more accurate diagnosis.
      The results showed that Nomarski interference contrast microscope provided
      clearer structures of oocysts in wet mount preparations than those under a normal
      light microscope and readily allowed distinction from yeast cells. Transmission
      electron microscopic study revealed that oocysts are thick walled and well
      sporulated. Their "untypical" appearance as seen by the light microscope resulted
      from sporozoites or the residuum that can be unfamiliar to some examiners.
      Electron microscopy provides definitive identification of Cryptosporidium spp.
      but Nomarski interference contrast microscopy was superior to bright field
      microscopy and may facilitate rapid diagnosis in routine fecal examination. The
      Ziehl-Neelsen modified acid fast technique was of value for differentiation and
      confirmation.

PMID- 1402462
TI  - Evaluation of a locally developed direct immunofluorescence test for chlamydial
      infections.
AB  - The high cost of diagnostic tests for chlamydial infections limits their use
      which may result in under estimation of the incidence of chlamydial infections.
      This study was an attempt to reduce the cost of the test by developing an
      immunofluorescence test for C. trachomatis using monoclonal antibody to major
      outer membrane protein of C. trachomatis. Urethral swabs were obtained from
      patients with symptoms of urethritis. The developed immunofluorescence test was
      compared with culture method and a commercial immunofluorescence test kit
      (BioMerieux). Compared with the culture method, the sensitivity, specificity,
      predictive value of positive and predictive value of negative of the developed
      test were 79, 85, 61 and 93 per cent respectively. The results obtained from the
      comparison with commercial test kit showed an agreement of 88 per cent. The
      developed test was positive in 32 per cent of specimens while the commercial test
      was positive in 24 per cent. The commercial test kit showed excellent reactions
      and it contained monoclonal antibody to lipopolysaccharide of Chlamydiae in
      addition to monoclonal antibody to major outer membrane protein which can lead to
      stronger immunofluorescence staining. The locally developed test, however, costs
      much less without compromising the results.

PMID- 1402463
TI  - Hematological and coagulation studies in malaria.
AB  - One hundred and twenty-six patients with malaria (30 cases of P. vivax and 96
      cases of P. falciparum) were studied for evidence of hematological coagulation
      and fibrinolysis abnormalities. Anemia associated with malaria was observed only
      in P. falciparum infections and there was no correlation between the degree of
      anemia and the percentage of parasitemia. Decreased hematocrit levels were found
      to be statistically significant in P. vivax infected patients (P greater than
      0.05). Thrombocytopenia was observed in both P. vivax and P. falciparum malaria
      patients (P less than 0.001) and correlated with the degree of parasitemia (r =
      0.974). Plasmin activity was normal in P. vivax malarial patients but it was
      significantly increased in patients with a P. falciparum of more than 5 per cent
      parasitemia. Coagulation profiles showed normal PT, aPTT, and TT in P. vivax
      infected patients while prolonged PT and aPTT were observed in P. falciparum
      infection which correlated with the degree of parasitemia (r = 0.0992).
      Coagulation factors V, VII, and IX were the most sensitive parameters in the
      expression of coagulation defects and most coagulation abnormalities were due to
      liver involvement. However, 2 of 20 complicated cases of P. falciparum showed
      evidence of disseminated intravascular coagulation (DIC).

PMID- 1402464
TI  - An unusual adhesion between red-cells and platelets in falciparum malaria.
AB  - A Thai female patient infected with P. falciparum had 80 per cent P. falciparum
      infected red cells at ring stage in the peripheral blood smear. The complications
      included anemia, thrombocytopenia, acute renal failure and pulmonary edema. A
      marked decrease in platelets number, low hemoglobin, low hematocrit and decreased
      red blood cell count were detected. More than 70 per cent of total platelets
      detected in the blood smear were binding to parasitized red blood cells. The
      number of binding platelets declined with decreasing per cent parasitized red
      cells. It was also noted that some platelets (10-20%) adhered to nonparasitized
      red cells. An increased number of large lymphocytes was shown by increased
      numbers of large unstained cells (LUC) by H* 1 automated analyzer. The peripheral
      blood smear showed abnormal binding of platelets to the infected red cells more
      frequently than to non infected red cells and free platelets on the day of high
      parasitemia. This abnormal phenomena was related to the number of platelets in
      the circulation. When the parasitized red cells were not detected in the blood
      smear, the number of platelets in the circulation had returned to normal.

PMID- 1402465
TI  - Immunological and immunopathological studies of patients with burn scar.
AB  - Sera obtained from 5 cases of burn scars (patients group 1) and cases of burn
      scars with squamous cell carcinoma (patients group 2) of the skin are analysed
      for anticollagen antibodies. Anticollagen type VI was demonstrable in the serum
      of one out of 5 cases in group 1 and 4 out of 6 cases in group 2. Collagen type
      VI was demonstrable in the scar without carcinoma of one patient whose serum
      contained anticollagen type VI. It is suggested that collagen type VI in the scar
      and their immunobiologic reaction may be related to the regulation of tumor
      development in scar tissue of the skin.

PMID- 1402466
TI  - Enzyme-linked immunosorbent assay for leptospirosis immunoglobulin M specific
      antibody using surface antigen from a pathogenic Leptospira: a comparison with
      indirect hemagglutination and microagglutination tests.
AB  - A search for a sensitive and specific test for human leptospirosis was made by
      enzyme-linked immunosorbent assay for immunoglobulin M specific antibody (IgM
      ELISA) using a surface antigen from L.interrogans serovar bataviae, L.
      interrogans serovar pyrogenes and L.interogans serovar icterohaemorrhagiae. The
      IgM ELISA tests using each of the three antigens were evaluated in 103 sera
      primarily positive by microagglutination test (MA). Optical density of these IgM
      ELISA tests showed good correlation. The IgM ELISA using antigen from serovar
      bataviae was compared with MA and indirect hemagglutination (IHA) in 20 sera
      primarily positive by IHA, and 103 sera primarily positive by MA. IgM ELISA and
      IHA using antigen prepared from serovar bataviae in 103 sera positive for MA had
      a sensitivity of 98.06 and 92.23 per cent respectively. In 20 sera primarily
      positive by IHA, IgM ELISA and MA showed sensitivity of 80 and 45 per cent
      respectively. The surface antigen used in IgM ELISA is broadly specific making
      IgM ELISA a sensitive and specific test for human leptospirosis. IHA agreed more
      with IgM ELISA in comparison to MA. As MA is not sensitive for early infection,
      IHA and IgM ELISA should be in routine use in general laboratories.

PMID- 1402467
TI  - Clinical features of acute lymphoblastic leukemia subclasses in 28 Thai children-
      a preliminary study.
AB  - Twenty-eight Thai children with newly diagnosed acute lymphoblastic leukemia were
      evaluated for pretreatment characteristic, including immunophenotype of
      lymphoblast, outcome of treatment, and the correlation among them. By APAAP
      technique using a panel of eight monoclonal antibodies (HLA-DR, CD 19, CALLA (CD
      10), IgM, CD 7, CD 3, CD 4, and CD 8), five subclasses were identified: 67.9,
      17.9, 7.1, 3.6, and 3.6 per cent were respectively shown to be common-, null-,
      mature thymocyte T-, pre B-, and B-ALLs. Clinical features in each subclass
      conformed to previous reports. All of the 27 evaluable patients attained initial
      complete remission, but subsequent relapses were noted in 7 patients (25.9%).
      Three of the 19 cases in the common ALL group relapsed at 6-12 months, whereas, 4
      of the 8 cases in the non-common ALL group relapsed at 2-15 months. Probability
      of relapse at 12 months in the common and non-common ALL groups were 19 and 49
      per cent respectively. Disease-free survival from time of remission was shorter
      in the non-common ALL group. Multivariate analysis of the 6 factors predicting
      disease-free survival showed that the only strong factor was the immunophenotype
      of lymphoblast.

PMID- 1402468
TI  - Immunophenotype and cytochemical reactions of acute lymphoblastic leukemia in
      Thai children.
AB  - The immunophenotypes of acute lymphoblastic leukemia (ALL) in 28 Thai children
      were studied by the APAAP technique using a panel of eight specific monoclonal
      antibodies: HLA-DR, CD 19, CALLA (CD 10), IgM, CD 7, CD 3, CD 4, and CD 8. Sixty
      eight, 18, 3.5, 3.5, and 7 per cent were respectively shown to be common, null,
      pre-B, B, and mature thymocyte T subtypes. Cytochemical reactions (beta
      glucuronidase, alpha naphthyl acetate esterase, and acid phosphatase) in this
      study could identify null, common, and T ALLs with confidence, and could be used
      in the process of ALL subtyping to reduce cost.

PMID- 1402469
TI  - Thalassemic red cells determined by different technology of blood cell analysers.
AB  - Blood samples from 12 normal cases and 30 thalassemic patients were analyzed by
      four blood cell analysers (the H*1, Baker 9,000RX, Coulter JT, and Argos). These
      four machines had different technology: light scattering using laser beam (H*1)
      and electronic aperture impedance (Baker 9,000RX, Coulter JT, and Argos).
      Analysis of normal blood samples showed comparable red cell parameters between
      these four machines except the value of RDW. When the thalassemic blood samples
      were determined using these four types of blood cell counters, many red cell
      parameters showed significant difference. This indicates that thalassemic red
      cells which are known as the abnormal cells in terms of their volume, shape,
      intracellular hemoglobin content, and osmotic fragility, responded differently to
      the reagents and technology of blood cell analysis. Calibration of the instrument
      using qualitatively abnormal blood sample, is recommended.

PMID- 1402470
TI  - Different cell volume with high target cell population between liver disease and
      homozygous hemoglobin E.
AB  - Blood samples with increased percentage of target cells were collected from liver
      disease, thalassemia, homozygous hemoglobin E (E/E), and nonidentified cases.
      Normal cases who had no history of liver disease and normal hemoglobin typing
      were also included in the study for control. Patients with liver disease had
      increased target cell percentage with normal MCV, whereas, the other three groups
      had increased target cell percentage and reduced MCV. The difference was more
      obvious when compared with liver disease and homozygous Hb E cases. These two
      groups had comparable target cell percentage (14.36 +/- 4.77 in liver disease,
      and 14.22 +/- 1.59 in homozygous Hb E) and comparable degree of anemia (Hb level
      in liver disease = 11.19 +/- 0.39, and 11.30 +/- 0.16 in homozygous Hb E) but
      they showed a statistical significance (p less than 0.0001) between MCV (79.66 +/
      2.18 fL in liver disease, and 60.40 +/- 0.75 fL in homozygous Hb E).

PMID- 1402471
TI  - Cytochemical reactions of homozygous beta-thalassemic spleens.
AB  - Splenic cells from 10 homozygous beta-thalassemic patients were stained using
      cytochemical reactions: non specific esterase and acid phosphatase. Spleens from
      nonthalassemic subjects: a normal case who underwent gastric surgery and 5
      idiopathic thrombocytopenic purpura, were also studied to serve as the control.
      In thalassemic spleens, no positive dot cell was shown in periarteriolar
      lymphocyte sheaths (PALS) when they were stained with both nonspecific esterase
      and acid phosphatase. In contrast, dot positive reaction was demonstrated in 92
      per cent of cells from a normal spleen. These cells were presumably T
      lymphocytes. There were two possibilities to explain our study 1) the absence of
      T lymphocytes in the PALS of white pulps in homozygous thalassemia may have an
      impact on the immune system related to infection complication in thalassemia 2) T
      lymphocytes in the thalassemic spleen may be present but they do not give a
      positive ANAE dot reaction.

PMID- 1402472
TI  - Cytometric analysis of paroxysmal nocturnal hemoglobinuria erythrocytes.
AB  - Erythrocytes from six cases of paroxysmal nocturnal hemoglobinuria (PNH) were
      analysed by the H*1 hematology analyser using laser inspection for each
      individual red cell. The computer program categorized the red cells into 9 groups
      based on the data of red cell volume and intracellular hemoglobin concentration.
      The only 46.3 +/- 10.9 per cent (Mean +/- SD) of PNH red cells were normochromic
      normocytic. Hypochromia (hemoglobin concentration less than 28 g/dL) with normal
      red cell volume (between 60 to 120 fL) were found in 22.8 +/- 19.7 per cent and
      with large cell volume (greater than 120 fL) = 14.9 +/- 4.5 per cent of total red
      cells. Large cells with normal hemoglobin concentration were found in 12.9 +/-
      13.2 per cent. The red cells had increased heterogeneity in red cell volume
      measured as red cell distribution width (RDW), Mean +/- SD = 23.6 +/- 2.3 per
      cent and increased heterogeneity in their hemoglobin concentration distribution
      with (HDW) (3.4 +/- 0.5 g/dL). The high RDW was resulted from increased number of
      varying size of macrocytes and the high HDW was caused by the increased number of
      hypochromic red cells. Heterogeneity in PNH red cell population described in this
      study has been postulated to relate with the clonal abnormality of the PNH red
      cells.

PMID- 1402473
TI  - Fetal red cell staining: method evaluation.
AB  - Acid elution methods have been extensively used for the identification of fetal
      red cells in pregnant women with fetomaternal hemorrhage. A number of methods
      have been described: Kleihauer-Betke, Boehringer Mannheim, Fetaldex, Nierhaus
      Betke modification and Sanguansermsri amido black B. A comparative evaluation of
      these methods was performed in this study. The technique of Sanguansermsri using
      amido black B was found to be more advantageous than the others in terms of
      simplicity, accuracy, precision and time taken.

PMID- 1402474
TI  - Measurements of cell volume and hemoglobin concentration of erythrocytes from
      hereditary ovalocytosis and hereditary spherocytosis.
AB  - Red cell analysis using the laser technique was done on erythrocytes from 11
      cases of hereditary ovalocytosis (HV) and one case of hereditary spherocytosis
      (HS). Heterogeneity in red cell volume measured as red cell distribution width
      (RDW) and heterogeneity of hemoglobin concentration in the red cells as measured
      by hemoglobin concentration distribution width (HDW) were analyzed. All of the
      studied cases showed abnormal increase in both RDW and HDW. The patient with HS
      had decreased MCV 77.4 fL (normal range = 80-99 fL). The HS patient had
      microcytes 14.7 per cent with markedly increased RDW 22.3 per cent (normal range
      = 11.5-14.5%). Increased hemoglobin concentration was demonstrated in HS red
      cells as shown by increased CHCM 39.2 g/dl (normal range = 33-37) with 5.86 g/dl
      of HDW (normal range = 2.2-3.3 g/dl). The HV patients had slightly decreased cell
      volume, MCV = 84.1 +/- 11.8 fL, with 9.2 +/- 10.1 per cent microcytes and 17.5 +/
      5.7 per cent RDW. Decreased hemoglobin concentration was shown in HV red cells
      as shown by decreased CHCM (31.7 +/- 1.9 g/dl) with slightly increased HDW (3.3
      +/- 0.9 g/dl). The HV patients had increased per cent hypochromic red cells (14.8
      +/- 18.6%). The ovalocytic red cells in HV patients had obviously reduced
      hemoglobin concentration compared to the spherical red cells of HS patients.

PMID- 1402475
TI  - Heterogeneity of antibody response to glomerular basement membrane antigen in
      patients with different forms of glomerulonephritis.
AB  - Antibodies to collagenous and noncollagenous components of glomerular basement
      membrane (GBM) have been detected by immunoblotting in some sera from patients
      with various kinds of glomerulonephritis. A half proportion of patients with
      rapidly progressive glomerulonephritis (RPGN), chronic focal glomerulonephritis
      (CFGN), idiopathic membranous glomerulonephritis (MGN). IgA nephropathy and lupus
      nephritis (LE-GN) had IgG antibodies to heterogenous components in acid insoluble
      fraction of pepsin digested GBM. This acid insoluble fraction represented a
      complex of collagen and noncollagenous proteins of GBM. Following digestion of
      acid insoluble fraction with bacterial collagenase, the triple helical
      collagenous components of GBM were destroyed and released most likely of
      noncollagenous proteins. Antibodies to this noncollagenous proteins were found in
      only some patients with chronic glomerulonephritis (17.6%) and lupus nephritis
      (21.4%). Upon reaction with human placenta derived type IV collagen, different
      frequencies of antibody response were found in patients of different groups.
      However, all these reactive sera showed a similar immunoblotting pattern. The
      relationship between antibody response to antigenic components from human GBM or
      human placenta and pathogenesis of renal disease is unclear. However, the
      occurrence of spontaneous autoantibody response to some exposed GBM self antigens
      may mediate further renal destruction resulting in chronic ongoing stage of the
      disease.

PMID- 1402476
TI  - Effect of vegetable oil intake on erythrocyte physical properties and
      hemorheology.
AB  - Effects of vegetable oil intake on red cell physical properties and blood flow
      condition were evaluated. The study was done on two groups of volunteers taking
      either soybean oil (6 volunteers) or palm oil (another 6 subjects) for a period
      of eight weeks. The continuous effects were followed up after continuing the
      vegetable oil intake for another four weeks. Significant reduction in red cell
      deformability was demonstrated by laser diffractometry in both groups. The palm
      oil had greater extent in causing reduced red cell deformability as early as four
      weeks after the oil intake, whereas, such effect was shown in eight weeks after
      the soybean oil intake. The reducing effect of red cell deformability by palm oil
      intake was more obvious than that by the soybean oil intake as indicated by the
      fall of deformability index from the control by 47.6 per cent in palm oil and
      21.9 per cent in the soybean oil group. The decrease still persisted and could be
      investigated on the four weeks' followup. The hematologic parameters measured by
      the laser-based instrument, the H*1 analyser were all within the normal ranges in
      both groups. However, the group taking soybean oil showed decreasing hemoglobin
      levels, which may be a physiological response to facilitate blood flow condition.
      The platelet volume was increased in both groups, indicating the possibility of
      adjustment of thrombopoiesis in the subjects although no clinical indication
      related to this finding was shown. In conclusion, intake of vegetable oil had an
      effect on red cell deformability. Soybean oil had an advantage over palm oil in
      having less effect on reducing the red cell deformability.

PMID- 1402477
TI  - Standardization of platelet aggregation test in normal Thai adults.
AB  - Platelet aggregation test was assessed by the turbidimetric method in 52 normal
      Thai adults consisting of 24 males and 28 females with ages ranging from 20 to 50
      years. The aggregating agents used were adenosine diphosphate (ADP), adrenaline
      and collagen. It was found that the ranges of threshold concentration of ADP,
      adrenaline and collagen which gave maximal induction of platelet aggregation were
      5-10 microM, 2.5-10 microM and 0.14-0.28 mg/mL, respectively. Collagen at the
      above concentration, showed lag phase within 2 minutes. This corresponds to that
      described in the reference method. Moreover, when induced by ADP and adrenaline
      53-65 per cent and 81-87 per cent of the subjects, respectively, showed biphasic
      curve. The above concentration of ADP, adrenaline and collagen are suitable for
      the study of platelet aggregation in normal Thai adults.

PMID- 1402478
TI  - Endomyocardial biopsy: a review of its current role and usefulness.
AB  - Endomyocardial biopsy via transvascular technique is safe. It shows a wide range
      of clinical applications. The fresh endomyocardial tissue thus obtained is very
      helpful for further research in the field of cardiac pathology. It facilitates
      almost all sophisticated techniques that need fresh and viable cells. Results of
      the study are relevant and mostly clinically useful. However, application of this
      technique to the study of heart diseases in Thai people is still limited. This
      may be partly due to excessive patient fear according to the general belief that
      the heart is the utmost important part of life. Other possible explanations
      include the doubt about the safety of this procedure and the benefit that they
      will receive. Then, any misunderstanding should be corrected and this technique
      should be encouraged when clinically indicated.

PMID- 1402479
TI  - Laboratory diagnosis of congenital and maternal rubella infection: a review.
AB  - Physicians are aware of the congenital rubella syndrome. Serodiagnosis is usually
      used to detect rubella infection in pregnant women and their fetuses. Although
      being considered the cornerstone of serodiagnosis, the hemagglutination
      inhibition test is gradually being replaced by new more convenient methods. Tests
      to detect IgM eliminate the need for paired sera to diagnose acute rubella
      infection. However, because of the possibilities of false positive, IgM results
      should be interpreted with caution. Detection of IgM in cord blood and new
      genetic technology made the diagnosis of infection in utero possible. The
      evidence of reinfection in people considered to be immune is abundant; however,
      discovering new antigenic determinants correlating with immunity may solve the
      problem and a new vaccine and antibody test that is truly associated with
      immunity will be available in the future.

PMID- 1402480
TI  - Rapidly progressive glomerulonephritis in Thai children.
AB  - Sixteen children with extensive crescentic glomerulonephritis and rapid renal
      deterioration were selected from 476 patients with glomerulopathy for study. The
      patients (1-14 yr, M:F = 5:11) presented with edema, oligoanuria, hypertension,
      gross hematuria and uremic symptoms in 81, 62, 62, 56 and 50 per cent,
      respectively. The mean Scr was 804 (+/- 436) micromole/L and BUN 38 (+/- 13.4)
      mmole/L. Anemia was found in 100 per cent, hematuria in 100 per cent, heavy
      proteinuria 75 per cent, hypoalbuminemia 40 per cent, hypercholesterolemia 38 per
      cent and low C3 40 per cent. The underlying causes of RPGN included idiopathic 9,
      PSAGN 6 and LE 1. Eight patients recovered with normal or slightly elevated Scr
      while the diseases progressed to ESRD in 8 patients. Idiopathic RPGN and
      extensive (greater than 80%) crescentic glomerulonephritis correlated with a poor
      prognosis.

PMID- 1402481
TI  - Combined Sarcocystis and gram-positive bacterial infections. A possible cause of
      segmental enterocolitis in Thailand.
AB  - Between 1981 and 1990, 22 intestinal specimens surgically resected due to
      segmental enterocolitis were collected and examined. Grossly, the specimens were
      classified into 3 groups 1) Acute inflammation with hemorrhage and necrosis 2)
      Constrictive lesion 3) False diverticulum with perforation. Mostly, there was
      unisegmental involvement, distributed in jejunum, ileum and ileocolon.
      Microscopically, small parasitic structures, interpreted to be unconventional
      excystation stage of Sarcocystis hominis, (Railliet and Lucet, 1891) Dubey 1976,
      were present on the luminal border and within the crypt-lining epithelial cells.
      At the ulcerated area, tissue invasion by Gram-positive bacteria were always seen
      and considered as second pathogen. Source of the parasite was likely from cyst
      containing beef available in markets, (Bos indicus and Bubalus bubalis) along
      with consumption of undercooked beef. Antismooth muscle antibody, IgG class, with
      the titer ranging from 1:16-1:256 were detected in 45 per cent of the patients.
      This is considered as autoimmunity against intestinal smooth muscle damaged
      previously from subclinical inflammatory condition. Present information suggests
      a long-standing existence of Sarcocystis in the patients' intestine, associated
      with Gram-positive bacterial infection, as the mechanism producing segmental
      enterocolitis found in the Central region.

PMID- 1402483
TI  - The preparation of lyophylised of fetal membrane for biological dressing.
AB  - The preparation of lyophylised fetal membrane was performed between November 1982
      and May 1984, and the membrane was applied to a variety of wounds. The result of
      the study was impressive, the biologic dressing property did fairly well, and the
      utilization of this fetal membrane was convenient in time and place.

PMID- 1402482
TI  - Tuberculous infection of the hand and the wrist.
AB  - Twenty cases of tuberculous infection of the hand and the wrist from the division
      of plastic reconstructive surgery over the past 17 years. There were fourteen
      males, and six females. The ages of the patients ranged from 10 years to 80
      years, with an average age of 50.1 years. The follow-up time was not less than 3
      years. The characteristic manifestation of this diseases was insidious onset, and
      run chronicity. Painful swelling of the wrist and fingers as well as increased
      sedimentation rate were frequent findings. However, confirmed histopathological
      diagnosis is essential. Surgical debridement together with triple anti
      tuberculous drugs are recommended. Triple drugs therapy should be given for not
      less than two years to prevent drug resistance and recurrence of the disease.

PMID- 1402485
TI  - Development of immune-complex glomerulonephritis and amyloidosis in Syrian golden
      hamsters infected with Opisthorchis viverrini.
AB  - Renal disease associated with Opisthorchis viverrini infection was investigated
      in Syrian golden hamsters. On the fourth week after infection with 100 viable
      metacercariae; anti-tegumental membrane antibodies were detected in the sera by
      immunofluorescence antibody technic and by enzyme-linked immunosorbent assay. Six
      weeks after infection tegumental and anti-tegumental membrane immune-complex and
      amyloid fibrils were found in the glomeruli. Amyloid was characterized to be AA
      protein. Acute proliferative glomerulonephritis associated with the brightest
      immune-complex deposits developed in week 8 after infection. Intensity of immune
      complexes in all glomeruli were reduce gradually thereafter and replaced by
      amyloid. Progressive obsolescence of the glomeruli, tubular atrophy, interstitial
      inflammation and fibrosis associated with massive proteinuria and deterioration
      of renal function appeared in week 10 after infection toward the end of the
      experiment in week 38 after infection.

PMID- 1402484
TI  - Fungal sinusitis the important role of the histopathology in the clinical
      management.
AB  - Four cases of fungal sinusitis are reported. These include one case of
      aspergillus sinusitis alone, one case of combined aspergillus and paecilomyces
      sinusitis, and two cases of mucormycotic (zygomycotic) sinusitis. Although fungal
      sinusitis appears to be rare, it can pose difficulty in clinical diagnosis and we
      have demonstrated how the pathologist can help to alert the otolaryngologists of
      possible fungal sinusitis. Since the histopathological examination is important,
      a specimen for biopsy is mandatory.

PMID- 1402486
TI  - Sarcocystis infection and actinomycosis in tumorous eosinophilic enterocolitis.
AB  - Intramural masses were resected from jejunum and ileocecal portion of a 49-year
      old, female patient with partial gut obstruction. Histopathological examination
      indicated the masses to be tumorous eosinophilic enterocolitis. Recent and late
      development phases of Sarcocystis in relation to bradyzoite infection have been
      observed and considered to be responsible for eosinophilic inflammation.
      Concomitant intestinal actinomycosis, known to produce tumorous lesion without
      eosinophilia, appears as an attractive natural model in producing tumorous
      eosinophilic enterocolitis. Pertaining to parasitic development, it is suggested
      that persisting sporulated oocyst may undergo spontaneous excystation in the
      host's intestinal wall, along with complex sporogony.

PMID- 1402487
TI  - Causes of perinatal death defined by autopsy at Ramathibodi Hospital.
AB  - Most causes of death during the fetal period are still unknown in all birth
      weight groups. Intrauterine anoxia evidence by clinical data and autopsy finding
      is the leading known cause in infants 1,001-2,500 g and over 2,500 g. In the
      early neonatal period in infants 1,001-2,500 g and over 2,500 g, the most common
      cause of death is congenital malformation which was also found as the main cause
      in the late neonatal over 2,500 g group. More than half of the deaths in the late
      neonatal period 1,001-2,500 g group, were caused by infection. Congenital
      syphilis and tetanus neonatorum which existed in the first study were not found
      in this study which reflects improved medical care.

PMID- 1402488
TI  - Prognostic factors of thyroid cancers in Ramathibodi Hospital.
AB  - The need to create different prognostic models for different populations is
      obvious after the findings that significant prognostic factors can change from
      one population to another. The purpose of this study is to fit a linear logistic
      model to a data set of Thai patients with thyroid cancers to find important
      prognostic factors and their effects on short-term mortality. Among the 89 cases
      selected, 20 died within 4 years after initial diagnosis and 69 survived more
      than 4 years. Age at diagnosis, sex, histological type and differentiation,
      microscopic vascular invasion, and extent of tumor spreading were included as
      independent variables. These variables were selected into the model by step-down
      selection procedure. Age at diagnosis was found to be the most significant
      prognostic factor followed by differentiation, vascular invasion and extent of
      spreading, respectively. However, vascular invasion appeared to exert the
      strongest impact on the prognosis with the risk of death increasing 62 fold for
      those showing microscopic evidence of this parameter. The odds ratios for the
      extent of spreading, age at diagnosis and differentiation were 7.5, 1.1 and 0.02,
      respectively.

PMID- 1402489
TI  - Changing terminology and screening recommendations in cervical cytology screening
      programs.
AB  - In summary, we have presented proposed new diagnostic terminology and screening
      frequencies for cervical cytology with some of the surrounding debate. As
      Thailand develops its own cervical screening program for squamous cell carcinoma,
      an awareness of these new recommendations may help in the design of a local
      program in the most cost effective manner.

PMID- 1402490
TI  - Blue nevus of the uterine cervix.
AB  - A case of an incidentally detected blue nevus of endocervix is presented. The
      nevus cells contained premelanosome and melanosomes. Pinocytotic activity, and
      interrupted basal lamina were disclosed by electron microscopic study. The
      histogenesis of these nevus cells from perineurial cells is discussed.

PMID- 1402491
TI  - Fatal paraquat poisoning: a light microscopic study in eight autopsy cases.
AB  - Eight autopsy cases of paraquat poisoning from 1980 to 1990 were studied by light
      microscopy. An attempt was made to correlate the severity of poisoning, as
      assessed by the blood paraquat concentrations and the time between ingestion and
      treatment, with the survival periods and pathological changes. Six of the
      patients were male. The mean age was 21 years (range 12-33 years). The blood
      paraquat concentrations on admission ranged from 0.04 to 4.27 micrograms/ml. The
      survival periods were between 26 hours and 59 days. The main causes of death
      included circulatory collapse in one patient with 26 hours survival, and acute
      alveolar injury of the lungs and acute tubular necrosis or diffuse cortical
      necrosis of the kidneys in 4 patients who survived less than 7 days. Pulmonary
      proliferative changes leading to respiratory failure were detected in the
      remaining patients, who survived 11, 17, and 59 days. The liver revealed bile
      duct injury in the portal areas, centrolobular cholestasis, fatty metamorphosis,
      and inconspicuous centrolobular hepatic necrosis. The adrenal glands showed
      diffuse cortical necrosis in 3 severe cases. Mild acute pancreatitis was evident
      in one case. The brain was edematous with or without focal minimal hemorrhages.
      Toxic myocarditis, myositis, and aplasia of erythropoiesis, as previously
      described, were not present in this study. The severity of poisoning seems to
      correlate reversely with the survival periods and directly with degrees of
      pulmonary damage and adrenal cortical necrosis.

PMID- 1402492
TI  - Does indication sheet reduce unnecessary urethral catheterization?
AB  - The study on the effect of indication sheet on the decision of doctors in
      ordering urethral catheterization was done in thirteen hospitals randomly
      selected from all regions of Thailand. 16,959 patients in medical and surgical
      wards were included between April and May 1989. The rates of urethral
      catheterization did not change by the influence of indication sheet. However,
      urethral catheterization without proper indications was reduced from 27.0 per
      cent in the control group to 14.3 per cent in the experiment group. The
      indication sheet was accepted in 96.5 per cent of the occasions when doctors
      prescribed urethral catheterization. The indication sheet changed the doctors'
      decision and hence reversed the order in 3 events (0.8%). It is concluded that
      indication sheet was well accepted by doctors and could reduce urethral
      catheterization without proper indications.

PMID- 1402493
TI  - Comparison of costs for disposable and reusable syringes and needles in Siriraj
      Hospital.
AB  - The costs for disposable and re-usable syringes and needles were compared in
      Siriraj Hospital, in July 1988. Data were collected from all wards regarding
      number of items used or replaced. Labour costs for recycling re-usable items were
      estimated by close observation. The costs for disposable and re-usable syringes
      and needles were 498,039.50, 193,874.45, 69,410.00 and 27,366.95 baht
      respectively. It can be concluded that re-usable items cost only 36 per cent of
      disposable ones. It is evident that re-usable syringes and needles should be
      appropriate for hospitals in Thailand at present.

PMID- 1402494
TI  - An alternative model for surveillance of nosocomial infections.
AB  - A modified method of administration of surveillance N.I. was introduced in
      Prapokklao Hospital, Chanthaburi, Thailand. Head nurses from all wards were
      recruited to survey N.I. By education, supervision and encouragement, the
      efficiency in surveillance gradually rose. The attack rate of N.I. by this method
      was only 2 per cent in 1986 when the project was started. The rate rose to 5.3
      per cent 2 years later. This model for surveillance shares the burden of the
      I.C.N. who are critically undermanned. The method was well accepted. Co-operation
      by medical personnel increased. This model is cost-effective and can be adopted
      by many hospitals in Thailand.

PMID- 1402495
TI  - Pre-operative shaving and wound infection in appendectomy.
AB  - The study on the effects of shaving the skin on wound infections after
      appendectomy was done in 80 patients in 1988 in Siriraj Hospital. Patients were
      divided randomly into two groups, 40 patients each, a control and an experiment
      group. The control group had their skin shaved and the experiment group did not.
      Data showed no difference in: demography, preoperative admission time, interval
      between skin preparation and surgery, thickness of subcutaneous tissue, operating
      time, and suture materials. Shaving of the skin resulted in no alteration in
      bacteria found on the skin, on the walls of the wound before closing. Stitch
      abscesses were the only wound infection found in 3 patients in each group. It is
      concluded that skin shaving, though it did not increase wound infection rate, had
      no beneficial effect on wound infection in appendectomy.

PMID- 1402496
TI  - Cross-infection of gentamicin-methicillin-resistant Staphylococcus aureus in a
      male surgical ward at Rajavithi General Hospital.
AB  - Between January and December 1987, gentamicin-methicillin-resistant strains of
      Staphylococcus aureus (GMRSA) were isolated from 7 patients in a male surgical
      ward at Rajavithi General Hospital. Six patients developed significant infection
      which included sepsis (2), pneumonia (1), infection in the eye, ear and wound
      (1), wound infection (2), and one patient had GMRSA isolated from his sputum. The
      strains were untypable with standard phage type and were resistant to
      methicillin, gentamicin, amikacin, kanamycin, streptomycin, tetracycline,
      erythromycin and chloramphenicol, but susceptible o vancomycin and cotrimoxazole.
      GMRSA were also isolated from bed-rail and the used rubber gloves left in the
      affected room. The GMRSA strains contained 5 plasmids of molecular weight of 18,
      11, 2, 1.8 and 1.7 Md. The 2Md plasmid coded for chloramphenicol resistance and
      the 1.8 Md plasmid for erythromycin resistance.

PMID- 1402497
TI  - Nosocomial infection control activities in Thailand 1989.
AB  - The study on the infection control activities was done in 89 general regional and
      community hospitals. Seventy-seven hospitals responded to the questionnaire
      (87%). All hospitals had set up infection control committees. Infection control
      nurses had been appointed in 84 per cent; 45 and 39 per cent were part-time and
      full-time ICNs respectively. Reports of surveillance were sent to the committees
      in 74 of the hospitals. Doctors took part in infection control in 75 per cent of
      the hospitals. Isolation units were available in 86 per cent and incinerators
      were installed in 13 per cent of the hospitals. These results indicate that the
      allocation of manpower and resources are not sufficient for effective nosocomial
      infection control.

PMID- 1402498
TI  - Precaution against nosocomial spread of cholera in Udornthanee Hospital.
AB  - From February to April 1988, there was an outbreak of cholera in Udornthanee
      Province. One hundred and twenty-four culture-documented cases were admitted into
      Udornthanee Hospital. Prevention of nosocomial spread of V. cholerae was done by
      the implementation of proper practices, surveillance culture and routine
      surveillance. There was no nosocomial spread of V. cholerae to patients or
      medical personnel. It was also shown that these practices were effective in
      prevention of contamination of the environment. It is concluded that simple
      measures are effective in the prevention of spread of V. cholerae in health care
      settings.

PMID- 1402499
TI  - The policy of the Ministry of Public Health on nosocomial infection control.

PMID- 1402500
TI  - HIV infection control in Thailand.

PMID- 1402501
TI  - The control of surgical sepsis.

PMID- 1402502
TI  - Microbiology for surveillance of nosocomial infections.

PMID- 1402503
TI  - Symposium: surveillance of nosocomial infections: problems in administration.

PMID- 1402504
TI  - Symposium: disposal of infectious hospital waste.

PMID- 1402505
TI  - Hospital acquired Janthinobacterium lividum septicemia in Srinagarind Hospital.
AB  - Nine patients admitted to the intensive care unit, Srinagarind Hospital, who had
      septicaemia by J. lividum were reported. Seven patients died, one directly of
      septicaemia, despite intensive antimicrobial therapy. Investigation revealed that
      the sources of infection were: special mouth wash solution, distilled water and
      normal saline used in the ward. After changing to uncontaminated solution and
      more meticulous care of medical equipment, there was no evidence of the micro
      organism after one year follow-up.

PMID- 1402506
TI  - Disposal of hospital infectious waste. The Hospital Infection Control Group of
      Thailand.

PMID- 1402507
TI  - Disposal of needles, syringes and gloves. The Hospital Infection Control Group of
      Thailand.

PMID- 1402508
TI  - Collection and transport of infectious specimens. The Hospital Infection Control
      Group of Thailand.

PMID- 1402509
TI  - Hospital food hygiene. The Hospital Infection Control Group of Thailand.

PMID- 1402510
TI  - Characteristic findings on the standard 12-lead ECG in patients with the
      fasciculoventricular Mahaim fiber.
AB  - Standard 12-lead electrocardiograms with a Q wave in lead V1 were obtained from
      32 subjects without organic cardiac disease and analyzed for features that might
      characterize an abnormal atrioventricular conduction through the
      fasciculoventricular Mahaim fiber. Following an infusion of ajmaline, the Q wave
      in V1 vanished abruptly and changed to an rS pattern in the 12 ajmaline
      responders. Discriminant analysis was performed to distinguish the ajmaline
      responders from the others. The explanatory variables were number of precordial
      leads with the abnormal Q wave, existence of the septal q waves, existence of the
      slurring of the Q wave in V1, existence of clockwise rotation, and existence of
      high voltage (RV5 + SV1 > 3.5 mV). Three variables, the absence of the septal q
      waves, the presence of the slurring, and the absence of clockwise rotation, were
      found to predict a positive response to ajmaline (discriminant probability =
      77%). These findings associated with the Q wave in V1 suggest that the
      fasciculoventricular fiber may be present.

PMID- 1402511
TI  - Variability in ECG computer interpretation. Analysis of individual complexes vs
      analysis of a representative complex.
AB  - Variability in the electrocardiogram (ECG) can be due to extrinsic noise or can
      be caused by intrinsic factors, such as changes in the volume conductor or in the
      heart itself. Computer programs for the interpretation of the ECG base their
      diagnostic classification on one set of measurements that is derived from a
      representative PQRST complex or that is computed by taking the median from the
      measurements for each complex in the recording. However, these methods may fail
      to do justice to the intrinsic variability that may be present in the ECG. An
      alternative method is proposed: derive a set of measurements from each complex in
      the recording, classify each individual complex separately, and then combine the
      individual classifications into one final classification. This procedure has been
      evaluated on a validated database (n = 1,220) using an ECG computer program.
      Total accuracy against the clinical evidence increased from 69.8% for the
      interpretations of the averaged complexes to 71.2% for the combined
      interpretations of the individual complexes (p < 0.001). The effect of beat-to
      beat variation on the measurements and classifications is demonstrated and the
      influence of extrinsic and intrinsic variability is assessed.

PMID- 1402512
TI  - ECG changes and cardiac arrhythmias in chronic renal failure patients on
      hemodialysis.
AB  - Serial 12-lead electrocardiogram (ECG) recordings and 24-hour Holter monitoring
      were carried out in 39 patients with chronic renal failure, starting just before
      a routine dialysis session. In an attempt to identify risk factors for cardiac
      arrhythmias, the results obtained from each patient were correlated with a
      variety of clinical, hematological, and biochemical data. All patients exhibited
      ECG changes, which were most pronounced during the first 2 hours of dialysis. The
      most frequent of these changes were a decrease in T wave amplitude and increase
      in Tmax time (all patients), an increase of QRS amplitude (61% of patients),
      shortened or prolonged QTc interval (61%) and ischemic-like ST-T changes (22% and
      39%, respectively). Potentially clinically significant arrhythmias occurred in 12
      patients (31%) of which 8 were supraventricular, 3 were combined ventricular and
      supraventricular, and 1 was pure ventricular. The only clinically identified risk
      factor for complex ventricular and supraventricular arrhythmia was advanced age.
      The arrhythmia and nonarrhythmia groups differed significantly in their
      predialysis hematocrit, O2 content, serum urea, and osmolarity, and in their
      postdialysis serum phosphorus and osmolarity. The results indicate that patients
      with chronic renal failure frequently exhibit ECG changes and a high incidence of
      ventricular and supraventricular arrhythmias, which may be prognostically
      significant, during and after hemodialysis.

PMID- 1402513
TI  - Use of the 12-lead ECG to detect myocardial reperfusion and salvage during acute
      myocardial infarction.
AB  - In this era of thrombolytic therapy, the standard 12-lead electrocardiogram (ECG)
      is easily available and noninvasive and could provide indicators of myocardial
      reperfusion and salvage. Previous reports have proposed that a decrease of total
      ST-segment elevation of > or = 20% from the pre- to the immediate posttreatment
      ECG is indicative of reperfusion, and that a > or = 20% decrease from the initial
      infarct size predicted by ST-segment deviation on the admission ECG to the final
      infarct size estimated by QRS score on the predischarge recording is indicative
      of myocardial salvage. This prospective study of 29 patients with myocardial
      infarction and angiographically documented reperfusion shows that the > or = 20%
      threshold for ST resolution achieved 79% sensitivity and 70% specificity in
      patients receiving intravenous therapy and 90% sensitivity in those receiving
      rescue intracoronary therapy. However, it should be noted that 21% of patients
      with successful intravenous therapy failed to achieve even this threshold of ST
      resolution. Regarding myocardial salvage, 63% of patients receiving intravenous
      and 90% of those receiving rescue intracoronary therapy achieved the threshold of
      > or = 20% decrease in infarct size.

PMID- 1402514
TI  - Effects of premature excitation and tachycardia on the spatial distribution of
      refractoriness and propagation of excitation in a computer model.
AB  - In this study, the spatial pattern of refractoriness and its effects on
      propagation of excitation during premature responses and tachycardia have been
      investigated using a computer model. The model simulated propagation, cycle
      length-dependent refractoriness, and slow propagation during the relative
      refractory period. Findings showed slow propagation near the origin of premature
      responses resulting in longer cycle lengths distal to the slowing. The nonuniform
      cycle lengths terminated by a premature response also represented the onset of
      the subsequent cycle, so the pattern of refractoriness was altered after both the
      premature and following cycle. This occurred even though cycle length affected
      only the immediately following refractory period in the model. The effect of
      nonuniform cycle lengths during a premature response on refractory periods after
      the subsequent response occurred with all cycle lengths of the later response.
      When the cycle length of that and further responses was sufficiently shortened to
      result in slowed propagation, changing spatial patterns of refractoriness and
      propagation occurred. The findings are evidence that responses with slow
      propagation during incomplete recovery of excitability can affect conduction
      velocity and refractoriness during multiple subsequent cycles. These effects are
      likely to occur in the heart but are modified by features such as sustained
      effects of cycle length on refractoriness, anisotropy, and electrotonic
      interactions.

PMID- 1402515
TI  - Resting and ambulatory ECG predictors of mode of death in dilated cardiomyopathy.
AB  - With the purpose of verifying whether the electrocardiogram (ECG) pattern alone
      can predict the mode of death in dilated cardiomyopathy, data from 12-lead ECGs
      and 48-hour arrhythmia monitoring were evaluated in 67 patients with dilated
      cardiomyopathy. During a mean follow-up period of 3 +/- 2 years, death from
      congestive heart failure occurred in 18 patients (27%), whereas 10 (15%) died
      suddenly (NS). Multivariate analysis showed that left bundle branch block (p <
      0.001) and left atrial enlargement (p < 0.001) were independently related to
      death from congestive heart failure. Ventricular arrhythmias of Lown grade 4A or
      4B (p < 0.001) and repolarization time, as assessed by QTc-QRS interval (p <
      0.05), were independent predictors of sudden death. It is concluded that ECG
      features alone may be helpful for risk factor characterization of dilated
      cardiomyopathy patients, provided that multiple ECG criteria are utilized at time
      of diagnosis.

PMID- 1402517
TI  - Small differences among body surface and epicardial QRST integral maps recorded
      during normal activation and experimentally simulated left bundle branch block or
      preexcitation in canine hearts.
AB  - QRST integral maps were constructed from 87-lead body surface electrocardiograms
      (ECGs) and from 45-lead epicardial electrograms during artificial pacing, which
      simulated left bundle branch block (LBBB) and Wolff-Parkinson-White syndrome in
      12 dogs. Although the ECGs and electrograms differed in configuration for each
      conduction model, the body surface and the epicardial QRST integral maps showed
      only small differences. Correlation coefficients (r) and root mean square
      differences (rms) were calculated to assess quantitatively the similarities in
      the QRST integral maps among the different conduction models. Mean r values
      between the normal conduction and the left bundle branch block models were 0.95
      in the body surface maps and 0.89 in the epicardial maps. Mean r values between
      the normal conduction and the Wolff-Parkinson-White ECG models were 0.97 in the
      body surface maps and 0.91 in the epicardial maps, and rms values were small
      enough. The small differences were also verified by the difference maps and by
      paired t tests. QRST integral maps on the epicardium and on the body surface were
      largely independent of altered activation sequences in both the left bundle
      branch block and the Wolff-Parkinson-White ECG models.

PMID- 1402516
TI  - Relationship of QRST isointegral maps during simulated left bundle branch block
      to impairment of left ventricular function due to myocardial infarction.
AB  - The clinical usefulness of QRST isointegral maps for assessing left ventricular
      (LV) dysfunction due to myocardial infarction (MI) in patients with MI in the
      setting of simulated left bundle branch block (LBBB) was investigated.
      Isointegral maps were recorded during sinus rhythm and right ventricular pacing,
      which simulated LBBB, in 62 patients with MI and 26 patients without MI. An
      abnormal decrease in the QRST value in the isointegral map was assessed by the
      difference map that indicated a "-2 SD area" where the QRST integral value was
      less than the normal range (mean - 2 SD) calculated from 608 normal individuals.
      The isointegral maps during the two activation sequences were similar in patients
      with and without MI (r = 0.87 and 0.92, respectively). The sum of QRST integral
      values less than the normal range (sigma DM) during simulated LBBB correlated
      significantly with the asynergy index, derived from left ventriculographic data
      (r = 0.81, p < 0.01). LV dysfunction (asynergy index > or = 2) was diagnosed in
      simulated LBBB with a sensitivity of 81%, specificity of 77%, and diagnostic
      accuracy of 80% when the criterion that LV dysfunction is present if the number
      of lead points in the -2 SD area exceeds 4, and a sensitivity of 71%, specificity
      of 81%, and diagnostic accuracy of 74% if sigma DM exceeds 200 mVms was used. The
      findings demonstrate that isointegral maps may be useful in assessing LV
      dysfunction due to MI in patients with MI and LBBB in addition to detecting the
      presence and site of MI in these patients.

PMID- 1402518
TI  - Comparison of ST depression recorded by Holter monitors and 12-lead ECGs during
      coronary angiography and exercise testing.
AB  - Data from previous studies are debatable regarding whether Holter monitors are a
      reliable electrocardiographic indicator of ischemia, for which the 12-lead
      electrocardiogram (ECG) is the standard. Simultaneous 12-lead and Holter ECGs
      were performed on 30 patients with typical angina pectoris during coronary
      angiography or exercise testing. ST depression recorded by both methods was
      directly compared, using the 12-lead ECG as the reference. The Holter tapes were
      also scanned by two automated ST analysis programs and the results were compared
      to 12-lead ECGs. Only 66 of the 178 12-lead ECG ST depression events were also
      present on the Holter recordings (37.1% Holter sensitivity). ST depression was
      underestimated by the Holter recordings compared to the 12-lead ECGs (p <
      0.0001). The majority (67.0%) of ST depression events identified by one computer
      program were false positive events. The degree of ST depression was overestimated
      compared to 12-lead ECGs by the second program (p = 0.0033). Holter-detected ST
      depression may not be a reliable ECG indicator of myocardial ischemia.

PMID- 1402519
TI  - The effect of stress and fatigue on cardiac rhythm in medical interns.
AB  - Twenty-four-hour ambulatory electrocardiographic monitoring was used to determine
      the incidence of arrhythmia while on-call and its relationship to stress and
      fatigue in 20 healthy medical interns. Mitral valve prolapse was present in 8 of
      19 interns (42%). Heart rates ranged from a maximum of 103-167 beats/min (135 +/-
      16) to a minimum of 38-61 beats/min (47 +/- 5). Interns had at least one episode
      of sinus tachycardia/h during 57% +/- 21% (range, 8-88%) of their hours on-call.
      Atrial premature beats (APB) were present in 19 of 20 (95%) and ventricular
      premature beats (VPB) in 12 of 20 (60%) subjects. APB/h ranged from 0 to 1.2 (0.4
      +/- 0.3) and VPB/h from 0 to 23 (2 +/- 6). Three interns had multiform VPB and
      two had ventricular couplets. More APB/h occurred in interns under greater stress
      (0.5 +/- 0.4/h vs 0.3 +/- 0.1/h, p < 0.05) and combined stress and fatigue (0.6
      +/- 0.4/h vs 0.2 +/- 0.2/h, p < 0.01). More VPB/h (5 +/- 9/h vs 0.5 +/- 0.6/h, p
      < 0.05) and higher (Lown) grade ventricular ectopy (2.3 +/- 1.6 vs 0.8 +/- 1.1; p
      < 0.05) occurred in interns under greater combined stress and fatigue. Mitral
      valve prolapse, sleep deprivation and caffeine intake were not associated with
      increased arrhythmia. The authors conclude that (1) rapid sinus tachycardia is
      frequent in interns while on-call and (2) interns experiencing greater stress and
      fatigue have more APB/h, VPB/h, and higher grade ventricular ectopy. These data
      support the notion that stress and fatigue may contribute to arrhythmia in
      healthy normal subjects.

PMID- 1402520
TI  - Autodecremental pacing for the interruption of ventricular tachycardia and atrial
      flutter.
AB  - The efficacy and safety of autodecremental pacing (ADP) to interrupt ventricular
      tachycardia (VT) and atrial flutter was examined. Once tachycardia was
      recognized, ADP was initiated using a short train of stimuli with gradual
      shortening (3%) of the interstimulus interval. ADP was applied to 13 consecutive
      patients during 75 episodes of VT (mostly following induction by ventricular
      stimulation). Successful interruption of VT occurred in 88% of the episodes. In 6
      episodes (8%), ADP resulted in ventricular fibrillation and in 3 episodes VT was
      unaffected by ADP. The only significant discriminator between the failure or
      success of ADP was the rate of VT. ADP was also applied to 17 consecutive
      patients with an atrial flutter that was resistant to conventional antiarrhythmic
      agents. Successful conversion of atrial flutter to sinus was seen in only 8
      patients (47%). A temporary acceleration to atrial fibrillation appeared in 3
      patients (18%), and in 6 patients atrial flutter was unaffected by ADP. ADP was
      successful in 70% (7/10) of patients with type 1 (< 300 beats/min) atrial
      flutter. The authors conclude that ADP is beneficial in the interruption of VT
      and atrial flutter in a selected group of patients, especially with a slower rate
      of tachyarrhythmia (atrial rate during atrial flutter < 300 beats/min and
      ventricular tachycardia < 180 beats/min).

PMID- 1402521
TI  - A 10-year follow-up study by orthogonal Frank lead ECG on patients with
      progressive muscular dystrophy of the Duchenne type.
AB  - A 10-year follow-up study by orthogonal Frank lead electrocardiography was
      performed on 25 patients with progressive muscular dystrophy of the Duchenne type
      (DMD). With advancing age, no apparent changes were observed in the duration and
      amplitude of the P wave or in the PR interval, whereas the duration of the QRS
      complex tended to increase. The amplitudes of the R wave in lead X (Rx) and lead
      Y (Ry) tended to decrease from 1.75 +/- 0.90 and 1.96 +/- 0.59 mV to 0.80 +/-
      0.63 and 1.39 +/- 0.62 mV (p < 0.01), whereas the amplitude of the S wave in lead
      X tended to increase from 0.24 +/- 0.23 mV to 0.53 +/- 0.36 mV in 10 years after
      initiation of the study (p < 0.01). It is noteworthy that the Ry amplitude began
      to decrease markedly from the seventh year after the initiation of this study,
      whereas the Rx amplitude showed a gradual and unceasing decline through the 10
      year period. Observation of the sequential changes of the QRS loops in three
      planes clearly demonstrated that the electrical force tended to decrease in the
      leftward and inferior directions and increase in the rightward direction. It is
      of interest that the frequency of occurrence of the deep Q wave was found to be
      quite high even in the early stages of DMD and that it did not display a direct
      relation to the sequential evolution of this disease. It can be concluded that
      observation of the sequential changes in the QRS complex allows estimation of the
      extent and direction of myocardial involvement in DMD.

PMID- 1402522
TI  - Mechanism of intermittent atrial parasystole.

PMID- 1402523
TI  - Ultra-high-resolution scanning electron microscopy of vaccinia virus and its
      recombinant carrying the gag gene of human immunodeficiency virus type 1.
AB  - FL cells infected with vaccinia virus or its recombinant carrying the gag gene of
      human immunodeficiency virus type 1 (HIV-1) were examined by ultra-high
      resolution scanning electron microscopy. Virions, whether located extracellularly
      or intracellularly, had a brick-shaped or watermelon appearance as a whole.
      Extracellular virions observed on the surface of infected cells had variable
      surface ultrastructures depending on the manner in which particular virions were
      wrapped in cell membranes. Most of the intracellular naked virions adherent to
      the inner face of cell surface membranes clearly exhibited ridgy, rod-shaped or
      globular surface structures on their surface. HIV-like particles with a diameter
      of about 100 nm and virions of vaccinia virus were both observed distinctly on
      the surface of FL cells infected with the recombinant virus.

PMID- 1402524
TI  - Mitochondrial breakage induced by the herbicide paraquat in cultured human lung
      cells.
AB  - Although the intracellular toxic sites of paraquat, a herbicide toxic to human
      bodies, have remained unclear for a long time, we recently demonstrated paraquat
      induced mitochondrial injury in rat lung and liver in vivo. In the present study,
      cultured human lung cells (A549 adenocarcinoma cell line) which received 0.15 mM
      paraquat (equivalent to 40 mg/kg i.v.) showed selective mitochondrial breakage at
      6-24 hr and died at 36-48 hr. These results suggest that mitochondria are the
      initial toxic site of paraquat in vitro as well as in vivo in contrast to the
      previously proposed microsome theory.

PMID- 1402525
TI  - Bioavailability: is this a key event in regulating the actions of peptide growth
      factors?

PMID- 1402526
TI  - Effects of transforming growth factor-alpha on chicken adipocyte precursor cells
      in vitro.
AB  - The hyperplastic capacity of adipose tissue resides in a group of fibroblast-like
      adipocyte precursor cells. There is evidence to suggest that their proliferation
      and differentiation is regulated by insulin-like growth factor-I (IGF-I) and
      transforming growth factor-beta (TGF-beta) but there is less information about
      other growth factors which may also participate in adipocyte precursor cell
      hyperplasia. Transforming growth factor-alpha (TGF-alpha) is a 50 amino acid
      polypeptide which has been shown to stimulate proliferation in both neoplastic
      and normal cell types acting through the epidermal growth factor (EGF) receptor.
      We have studied the regulation of DNA synthesis and the activity of lipoprotein
      lipase by TGF-alpha in chicken adipocyte precursor cells in vitro. Both TGF-alpha
      and EGF stimulated incorporation of [3H]thymidine into DNA in a dose-dependent
      manner. TGF-alpha was approximately 180-fold more potent than EGF. Addition of
      TGF-alpha in combination with IGF-I, TGF-beta 1 or platelet-derived growth factor
      produced a synergistic increase in DNA synthesis. Short-term incubation with TGF
      alpha reduced lipoprotein lipase activity by 23%. These results show that TGF
      alpha is a potent mitogen in these adipocyte precursor cells and can inhibit
      their differentiation in vitro and may participate in the regulation of adipose
      tissue development in vivo.

PMID- 1402527
TI  - Effects of the daily administration of gonadotrophin-releasing hormone on the
      anterior pituitary gland of rats with restricted feeding.
AB  - To investigate the influence of weight reduction on pituitary function and its
      modulation by gonadotrophin-releasing hormone (GnRH), female rats were restricted
      to 10 g food/day for 60 days. GnRH (5 micrograms) or saline (0.2 ml) were
      administered daily between days 31 and 60 of the period of underfeeding.
      Underfeeding brought about a decrease in the pituitary gonadotrophin content,
      serum levels of gonadotrophins and oestradiol, and the number and size of both LH
      and FSH-positive pituitary cells. The administration of GnRH to underfed rats
      produced an increase in the pituitary and serum gonadotrophin levels and the
      number and size of both LH- and FSH-positive pituitary cells. These observations
      suggest that underfeeding and/or weight loss diminish the number and activity of
      the pituitary gonadotrophs, and that daily administration of GnRH both increases
      the number of gonadotrophs and augments their activity.

PMID- 1402528
TI  - Metabolism of dihydrotestosterone to 3 alpha-androstanediol in brain and plasma:
      effect on behavioural activity in female rats.
AB  - Six experiments were carried out to determine whether dihydrotestosterone (5
      alpha-androstan-17 beta-ol-3-one; DHT) acts to inhibit oestradiol (OE2)-induced
      lordosis behaviour after its metabolic conversion to 5 alpha-androstane-3
      alpha,17 beta-diol (3 alpha-androstanediol, 3 alpha-Adiol). In experiments 1 and
      2, ovariectomized rats were treated with several doses of DHT or 3 alpha-Adiol,
      injected with OE2 and progesterone, and tested for lordosis responsiveness.
      Significant inhibition of lordosis occurred after a dose of 3 alpha-Adiol which
      was approximately threefold less than the effective DHT dose. In experiments 3
      and 4, plasma concentrations of DHT and 3 alpha-Adiol were measured after the
      injection of these steroids to ovariectomized rats at doses shown to be both
      sufficient or insufficient to inhibit lordosis. Behaviourally effective dosages
      of DHT and 3 alpha-Adiol produced circulating concentrations of 3 alpha-Adiol
      greater than those produced by behaviourally ineffective doses of DHT or 3 alpha
      Adiol. At 30 min after injection of DHT (experiment 3), 78.8% of plasma androgens
      were in the form of 3 alpha-Adiol, while after injection of 3 alpha-Adiol, only
      7.4% were DHT. When plasma DHT and 3 alpha-Adiol were measured at 3, 6, 9 and 12
      h after steroid injection (experiment 4), plasma levels of 3 alpha-Adiol produced
      by the behaviourally subthreshold dose of DHT were significantly lower than
      levels produced by behaviourally sufficient dosages of DHT or 3 alpha-Adiol. In
      experiments 5 and 6, concentrations of DHT and 3 alpha-Adiol were measured in
      five brain regions 1 and 6 h after injection of behaviourally sufficient doses of
      these steroids to ovariectomized females. At 1 h after injection, similar levels
      of DHT and 3 alpha-Adiol were measured in DHT- and 3 alpha-Adiol-injected
      females, and DHT concentrations in the preoptic area were significantly higher in
      both groups than in any other brain area. At 6 h, animals injected with DHT had
      significantly higher levels of DHT in all brain areas combined than did 3 alpha
      Adiol- or vehicle-injected animals. Brain concentrations of 3 alpha-Adiol were
      not different between groups injected with DHT, 3 alpha-Adiol or vehicle at this
      time. In brain, 34.6% of DHT had been converted to 3 alpha-Adiol after 1 h and
      53.0% of 3 alpha-Adiol had been converted to DHT.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 1402529
TI  - Lung to blood passage of human growth hormone after intratracheal instillation:
      stimulation of growth in hypophysectomized rats.
AB  - The passage from the lower respiratory tract into the blood of human GH (hGH;
      M(r) = 22,000) and bovine serum albumin (BSA; M(r) = 67,000) was assessed after
      intratracheal instillation in adult rats. The plasma level of immunoreactive hGH
      reached its maximum at 0.5-1 h after instillation and had almost disappeared
      within 24 h. Higher plasma levels were obtained in male rats than in female rats
      resulting in a higher total lung passage of hGH in male rats than in female rats
      (means +/- S.D.; 6.0 +/- 1.7% vs 3.3 +/-1.2%, P<0.01). The plasma level of BSA
      showed a different pattern, with a maximum at 16-24 h after instillation and a
      total lung passage of 4.3 +/- 1.7% of the given dose for both sexes. The plasma
      levels of hGH increased nonlinearly with increasing dose instilled in the dose
      range 36-720 micrograms/kg body weight. When hGH was instilled daily at a dose of
      720 micrograms/kg body weight to hypophysectomized rats for 1 week, they
      responded with a significant increase in body weight when compared with
      hypophysectomized control rats (16.8 +/- 4.2 g vs -1.8 +/- 2.4 g, P<0.001). The
      results demonstrate that, despite their different molecular weights, hGH and BSA
      pass through the lower respiratory tract into the circulation with similar
      efficiencies in the rat. However, the lung passage of hGH, unlike that of BSA,
      showed sexual dependency, an earlier plasma concentration maximum and a tendency
      of the passage to saturation with increasing dose instilled.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1402530
TI  - Cytotoxic factor in the serum of diabetic rats and its increase during pregnancy.
AB  - Diabetic pregnancy is associated with a high incidence of fetal growth
      abnormalities which cannot be solely ascribed to fetal hyperglycaemia and
      hyperinsulinaemia. We therefore examined the possibility of other contributing
      factors using rats made diabetic with streptozotocin as the experimental model.
      Blood serum from virgin diabetic rats and, to a much greater extent, from
      pregnant diabetic rats inhibited [3H]thymidine incorporation by fetal lung cells
      in culture in a concentration- and time-dependent manner; cell number was also
      decreased. The cytotoxic activity of the serum was decreased by treatment of
      pregnant diabetic rats with insulin. Sera from non-diabetic rats and from rats at
      6 h and 24 h after the injection of streptozotocin were not cytotoxic. The
      cytotoxic activity of diabetic rat serum was retained after dialysis and was not
      destroyed by heating it for 60 min at 60 degrees C. Diabetic rat serum
      antagonized the stimulatory effects of fetal bovine serum, insulin and insulin
      like growth factors on thymidine incorporation by lung cells and inhibited
      corticosterone production by adrenal cells. Ultrafiltration of diabetic rat serum
      and high-performance gel permeation chromatography in phosphate buffer suggested
      that the molecular weight of the cytotoxic factor was approximately 40 kDa.
      However, gel permeation chromatography in 40% acetonitrile of the cytotoxic
      eluate from reversed-phase high-performance liquid chromatography using a C18 and
      C4 column revealed that the cytotoxic factor was a low molecular weight
      substance, which contained no amino acids. The apparent discrepancy in molecular
      weights using different separation procedures suggests that the cytotoxic factor
      is bound to serum proteins. The u.v. spectrum of this factor was different from
      those of ketone bodies but its exact chemical identity could not be established
      because of the scarcity of the material. It is suggested that the sera of
      pregnant diabetic rats and their fetuses contain a cytotoxic factor, which may
      contribute to fetal developmental abnormalities.

PMID- 1402531
TI  - Interaction between thyrotrophin-releasing hormone and the muscarinic cholinergic
      system in rat brain.
AB  - TRH increases the pressor response to acetylcholine through an increment in
      muscarinic receptors. As chronic atropinization produces a similar effect, we
      hypothesized that both phenomena may be related. The effect of chronic atropine
      treatment on the TRH content of several brain areas in Wistar rats was studied.
      Atropine produced significant increases in TRH content in the preoptic and septal
      areas, while decreases were observed in the hypothalamus and hypophysis. The
      concentration of TRH in cerebrospinal fluid rose significantly in atropine
      treated rats compared with controls. A similar effect was observed with eserine,
      an acetylcholinesterase inhibitor. Finally, perfusion of brain preoptic area
      slices from normal rats with Krebs-Ringer solution in the presence of pilocarpine
      increased basal TRH release significantly and this effect was blocked by
      atropine. These results are compatible with a muscarinic control on the activity
      of the central TRH system.

PMID- 1402532
TI  - Preparation and characterization of an antibody specific to the rat dopamine D2
      receptor.
AB  - Antibodies specific to the dopamine D2 receptor have been raised in rabbits using
      synthetic peptides. The resulting antiserum was sensitive to picogram quantities
      of peptide as measured by enzyme-linked immunoassay and was shown to have a 33%
      cross-reactivity with partially purified D2 receptor protein. No detectable cross
      reactivity with similarly prepared fungal membranes was observed. D2 receptor
      preparations from normal rat pituitary cells were used in Western blot analysis.
      Bands of M(r) = 95,000 and 34,000 were detected in these preparations with a
      third faint band at 120,000. These correspond to the pituitary D2 receptor.

PMID- 1402533
TI  - Changes in the plasma concentration of gastric inhibitory polypeptide and other
      metabolites in response to feeding in sheep.
AB  - Plasma concentrations of gastric inhibitory polypeptide (GIP)-like activity were
      determined in sheep before and after refeeding following a 48-h fast. Plasma
      concentrations increased significantly after feeding, from about 250 pg/ml to
      about 550 pg/ml. Other metabolites in plasma also increased at this time,
      reflecting the absorption of nutrients from the gastrointestinal tract.
      Significant increases were observed in the plasma concentrations of acetate, beta
      hydroxybutyrate and triacylglycerol. By comparing the time-courses of the changes
      in concentration of GIP and other metabolites in plasma, possible sites of
      secretion and secretagogues of GIP in ruminant animals are proposed. The results
      demonstrate that GIP is secreted in response to nutrient absorption in adult
      ruminants and that, as in simple-stomached animals, the absorption of long-chain
      free fatty acids plays an important role in this secretion.

PMID- 1402534
TI  - Influence of lactotroph cell density on prolactin secretion in rats.
AB  - The relationships between the stimulation of prolactin secretion and
      proliferation of lactotrophs was studied from a multidisciplinary standpoint in
      three experimental models. Administration of both oestrogen and sulpiride
      resulted in a significant increase in prolactin secretion and in the lactotroph
      population. A single injection of 10 micrograms oestradiol benzoate (OB) induced
      a twofold increase in the proliferation of lactotrophs (morphometrically as
      volume density), which increased further (2.5-fold) after three OB injections.
      Parallel changes were observed in the net counts made on lactotrophs sectioned
      through the nucleus to avoid possible distortions in volume density caused by
      hypertrophic cytoplasms. Comparable results were obtained with the mitotic index
      in the same groups of rats exposed to treatment with colchicine. The effect of
      sulpiride on proliferation of lactotrophs was also significant (1.7-fold) but
      less pronounced than in rats treated with oestrogens. The treatments with
      oestrogen and sulpiride did not stimulate lactotrophic activity in a similar way,
      as judged by the levels of serum prolactin and the storage patterns of small and
      big prolactin in pituitary glands. Serum prolactin (mean +/- S.E.M.) in control
      ovariectomized rats was 4.0 +/- 0.9 micrograms/l and one and three injections of
      OB raised these levels to 14.4 +/- 5.0 and 28.8 +/- 4.6 micrograms/l
      respectively. The highest levels of serum prolactin were seen in sulpiride
      treated rats (467.2 +/- 28.7 micrograms/l). Striking differences occurred in the
      pituitary contents of big prolactin, the control values increasing from 5.3 +/-
      0.5 to 10.2 +/- 1.3 micrograms/mg after one OB injection and to 14.7 +/- 0.7
      micrograms/mg after three OB injections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402535
TI  - In-vitro DNA synthesis in Leydig and other interstitial cells of the rat testis.
AB  - Replicative DNA synthesis (125I-labelled iododeoxy-uridine incorporation) was
      measured in interstitial cells prepared from rat testes and separated by Percoll
      density gradient centrifugation. Leydig cells were identified by 125I-labelled
      human chorionic gonadotrophin (hCG) binding and 3 beta-hydroxysteroid
      dehydrogenase histochemistry. Continuous density gradients indicated that
      interstitial cell DNA synthesis was not associated with Leydig cells, and was
      greater in cells from the immature than from the mature rat testis. Fractionation
      of cells by discontinuous density gradients into Leydig cell-rich and -depleted
      pools did not result in a similar enrichment of DNA synthesis. Treatment of the
      adult rat with hCG increased DNA synthesis into both fractions but oestrogen had
      no effect. DNA synthesis was greater in cells from the immature rat but, in
      contrast to the adult, in-vivo hCG treatment had no effect, whilst oestrogen
      decreased synthesis. To characterize the cells synthesizing DNA further,
      interstitial cells were prepared from testes in which the Leydig cells were
      depleted by in-vivo treatment with ethane dimethanesulphonate (EDS) or depleted
      in their germ cells by treatment in utero with busulphan. EDS treatment had no
      effect on DNA synthesis by the interstitial cells in spite of the 125I-labelled
      hCG binding being markedly reduced. Similarly, busulphan treatment was also
      without effects upon DNA synthesis. Fluorescence-activated cell cycle analysis of
      cells from both fractions from germ cell-depleted testes indicated that only a
      small proportion (3%) of the interstitial cells were actively dividing and this
      was almost doubled in cells from the germ cell-depleted immature rat
      testes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402536
TI  - Abnormal maternal behaviour in mice previously immunized against progesterone.
AB  - Anti-progesterone immunization leads to reversible infertility in mice; this can
      be achieved by passive immunization with a monoclonal antibody to progesterone
      (DB3), or by active immunization with either a progesterone-protein (bovine serum
      albumin; BSA) conjugate or anti-idiotype directed against DB3. Recovery of
      fertility in treated females varied from 39.5 to 75.5 median days after passive
      or active (progesterone-BSA) immunization respectively. Litter size after the
      first pregnancy also differed from 8.6 +/- 0.8 to 5.0 +/- 0.6 (mean +/- S.E.M.)
      per mother after passive or active immunization respectively. When litter size
      was standardized to a maximum of four pups per litter, aberrant maternal
      responses were observed in the first 5 days after delivery in 40-70% of the
      nursing mothers. These responses took the forms of cannibalism and failure to
      retrieve or to nurse pups and resulted in a high incidence of pup rejection (up
      to 40%), compared with no rejection in control mothers. When mothers were allowed
      to keep entire litters, an even higher incidence of pup rejection occurred (51%
      compared with 8% in controls). There was an apparent relation between the degree
      of negative maternal behaviour and the progesterone antibody concentration in the
      circulation during the infertile period. Whereas aberrant behaviour occurred
      mainly within the first 5 days of lactation, it was significantly reduced
      thereafter. Aberrant behaviour of the mother towards pups may be a consequence of
      the presence of residual progesterone antibodies in the circulation which affects
      the process of progesterone withdrawal at parturition that is essential for the
      establishment of normal maternal responses to the neonate.

PMID- 1402538
TI  - Hypothalamic-pituitary function in neonatally oestrogen-treated male rats.
AB  - Neonatal oestrogen administration to male rats permanently impaired the function
      of the pituitary-testicular axis possibly by inhibiting neonatal gonadotrophin
      secretion. To analyse the hypothalamus and/or pituitary involvement in this
      inhibition, pituitary responsiveness to acute stimulation with LH-releasing
      hormone (LHRH) was studied in vivo and in vitro in Wistar male rats injected on
      day 1 of age with oestradiol benzoate (OB) or olive oil. FSH and LH pituitary
      content and plasma concentrations were reduced in oestrogenized male rats at days
      10 and 16 of age. Likewise, the in-vivo increase in gonadotrophin plasma
      concentrations after acute stimulation with LHRH was almost completely suppressed
      in 10- and 16-day-old oestrogenized males. In vitro, the increased secretion of
      FSH after LHRH stimulation was abolished and the LH response strongly reduced in
      pituitaries from oestrogenized males. Finally, the effects of neonatal
      oestrogenization were not abolished by treatment from day 1 to day 15 with an
      LHRH agonist (0.01 microgram/kg per 12 h). We conclude that in male rats the
      effects of oestrogenization are due to both a reduction in LHRH endogenous
      secretion and a decrease in the pituitary responsiveness to LHRH.

PMID- 1402537
TI  - Pituitary-testis function in rats treated neonatally with a gonadotrophin
      releasing hormone agonist: short- and long-term effects.
AB  - Acute and long-term effects of neonatal and prepubertal treatments with an LH
      releasing hormone agonist (LHRH-A) were studied in Wistar male rats. Animals
      injected with D-Ala6-D-Gly10-LHRH ethylamide (2 micrograms/kg per day) or vehicle
      from days 1 to 15 or from days 16 to 29 were killed at different ages. Treatment
      between days 1 and 15 induced a decrease in both pituitary FSH and LH content as
      well as a reduction in plasma FSH and blockade of the response to LHRH. These
      effects were apparent on day 16 after treatment. Basal and human chorionic
      gonadotrophin (hCG)-stimulated progesterone and testosterone secretion in vitro
      was similar in testes from male rats treated with LHRH-A or vehicle. Reduced
      testicular weight was observed until day 90, whereas puberty, spermatogenesis and
      fertility were unaffected. The decrease in plasma FSH concentrations after
      neonatal treatment with LHRH-A was also found in groups of animals killed on day
      10 and was possibly the cause of reduced testicular weight, since treatment with
      FSH from day 1 to day 15 blocked the effect of LHRH-A. Likewise, treatment with
      LHRH-A from day 1 to day 15 also reduced FSH and LH secretion in males
      orchidectomized on day 1 of life. Animals injected with LHRH-A from day 15 to day
      29 exhibited, at the end of the treatment period, reduced testicular weight, and
      decreased pituitary gonadotrophin content and plasma FSH concentrations, whereas
      LH plasma concentrations were normal. In adulthood, the pituitary-testis function
      did not vary from normal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402539
TI  - Bioactive and immunoreactive FSH and immunoreactive inhibin concentrations in the
      ovine fetus.
AB  - The bioactive (B) and immunoreactive (I) pituitary contents/concentrations of
      FSH, together with the plasma concentrations of B-FSH, I-FSH and I-inhibin were
      determined in ovine fetuses at days 55, 75, 90 and 135 of gestation (day 145 =
      term). The pituitary contents and concentrations of B-FSH and I-FSH increased in
      both sexes with gestational age. The female fetuses had significantly (P < 0.01)
      higher pituitary contents/concentrations of B-FSH and I-FSH than the male fetuses
      at days 75 and 135. The pituitary B/I ratios of FSH were not significantly
      different with age or sex. The plasma concentrations of B-FSH remained relatively
      constant from days 75 to 135, with no significant differences between sexes or
      with age. In contrast, the plasma concentrations of I-FSH reached a peak at day
      90 and then declined towards term in both sexes. At all gestational ages except
      day 55, the female fetuses had significantly (P < 0.05) higher plasma
      concentrations of I-FSH than the males. In both sexes, the plasma B/I ratios of
      FSH were lowest at day 90 and had increased again by day 135, with the male
      fetuses having significantly (P < 0.05) higher B/I ratios compared with the
      female group at days 75 and 135 but not at day 90. At all gestational ages, the
      plasma concentrations of I-inhibin declined throughout gestation in the female
      fetuses, whereas in the males they reached a nadir at day 75 and then increased
      towards term. The concentrations of I-inhibin were significantly (P < 0.01)
      higher in the male fetuses compared with the females.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402540
TI  - Receptor binding and growth-promoting activity of insulin-like growth factor-I in
      a bovine mammary epithelial cell line (MAC-T3).
AB  - Insulin-like growth factor-I (IGF-I) has been known to be mitogenic to a variety
      of cell types, although a growth-regulatory role for IGF-I on bovine mammary
      epithelial cells has not been fully investigated. In the present study, we
      examined the receptor binding of IGF-I and its effect on growth in a bovine
      mammary epithelial cell line (MAC-T3). Specific receptors for IGF-I were detected
      on cultured bovine mammary epithelial cells. Competitive binding revealed that
      half-maximal inhibition of 125I-labelled IGF-I binding by IGF-I was approximately
      3 micrograms/l. Dissociation rate constant of the IGF-I receptor was 3.10 +/-
      0.06 nmol/l (S.E.M.) with a receptor site concentration of 366 +/- 8 fmol/mg
      protein for the average of three experiments. IGF-I exerted a positive mitogenic
      effect on MAC-T3 cells according to both direct DNA assay and thymidine
      incorporation assay. Moreover, the mitogenic effect of IGF-I on MAC-T3 cells was
      enhanced by the addition of fetal calf serum in the culture media. The present
      results suggest that the bovine mammary epithelial cell line (MAC-T3) provides a
      useful model system with which to study the biological actions of insulin-like
      growth factors on the bovine mammary secretory tissue in vitro.

PMID- 1402541
TI  - Distribution of relaxin between human maternal and fetal circulations and
      amniotic fluid.
AB  - Relaxin was measured in maternal blood and amniotic fluid samples at 9-40 weeks
      and in fetal blood samples at 19-41 weeks of pregnancy. In amniotic fluid,
      concentrations of relaxin rose from 58 ng/l (geometric mean) at 10 weeks to 142
      ng/l at 14 weeks and declined subsequently to 55 ng/l at 22 weeks. In maternal
      blood, mean relaxin concentrations were ten times greater than in amniotic fluid,
      and concentrations decreased with gestation. Since there was no significant
      association between the relaxin concentrations in the two compartments, relaxin
      in the amniotic fluid may be derived from the decidualized endometrium rather
      than the maternal circulation, alternatively its metabolism may be different in
      the two compartments. The absence of detectable concentrations of relaxin in any
      of the fetal blood samples demonstrates that there is no significant placental
      transfer or fetal synthesis of this peptide.

PMID- 1402542
TI  - Embryonic mortality and the uterine environment.

PMID- 1402543
TI  - Stress and the hypothalamo-pituitary-adrenal axis: acute, chronic and
      immunological activation.

PMID- 1402544
TI  - Apparent alpha-inhibin subunit immunoactivity in porcine and ovine luteal
      extracts is due to interference by cytosolic proteases in the assay.
AB  - Immunoreactive alpha-inhibin (ir-inhibin) was measured in luteal homogenates and
      subcellular fractions of ovine and porcine corpora lutea (CL) and in pig
      granulosa cells (GCs), using a sensitive radioimmunoassay specific for the 1-26
      amino acid sequence of the N-terminus of the alpha chain of porcine inhibin (p1
      26 alpha-inhibin). Inclusion of N-ethylmaleimide (N-EM) and/or EDTA in the
      immunoassay had no effect on the measurement of p1-26 alpha-inhibin peptide
      standards, on ir-inhibin levels in ovine follicular fluid and serum, or on ir
      inhibin in subcellular fractions of pig GC. Fractionation of porcine GC
      homogenates on sucrose gradients demonstrated a major particular peak of ir
      inhibin (buoyant density, 1.15-1.21 g/cm3) with variable activity in the cytosol.
      The particulate ir-inhibin peak was released into the cytosol by pretreatment of
      GC homogenates with the saponin, digitonin, prior to fractionation. Porcine GC
      extracts contained a protein (M(r) 45,000) which immunoblotted against p1-26
      alpha-inhibin antibody. In the absence of inhibitors of proteolysis, apparent ir
      inhibin activity was very high in extracts of sheep and pig CL. However,
      inclusion of N-EM or EDTA in the radioimmunoassay significantly reduced ir
      inhibin levels in porcine and ovine CL extracts in a dose-dependent manner.
      Measurements of peptide tracer integrity indicated that porcine luteal cytosol
      degraded 125I-labelled p1-26 alpha-inhibin peptide. Subcellular fractionation
      studies demonstrated high levels of apparent ir-inhibin in luteal cytosol
      fractions, with only minor activity peaks associated with particulate fractions;
      however, this material was not releasable by digitonin. Immunoblotting of
      detergent extracts of porcine luteal particulate fractions failed to demonstrate
      alpha-inhibin material, and immunocytochemical localization studies of alpha
      inhibin in porcine and ovine luteal sections were negative. Our results are
      consistent with the intracellular packaging/storage of a form of alpha-inhibin
      (M(r) similar to that of alpha-inhibin subunit precursor) in the porcine
      granulosa cell. However, luteinization of the porcine follicle was associated
      with a dramatic fall in ir-inhibin content, and the loss of immunostaining for
      alpha-inhibin peptides. We conclude that porcine and ovine CL contain little, if
      any, authentic inhibin. These studies emphasize the importance of excluding
      proteolytic artefacts when measuring biological peptides in luteal tissue
      extracts by radioimmunoassay.

PMID- 1402546
TI  - Regulation of female brain aromatase activity during the reproductive cycle of
      the dove.
AB  - Oestrogen is formed in the female dove brain. The aim of this study was to
      determine whether (a) the catalytic properties of the brain aromatase are similar
      to the ovarian enzyme and (b) aromatase activity in the female brain changes
      during the reproductive cycle and is influenced by steroids and environmental
      stimuli. The results show that female preoptic aromatase has a higher substrate
      affinity than the enzyme in ovarian follicles (apparent Km: preoptic area, 7
      nmol/l; ovarian follicles, 29 nmol/l), but a lower activity in the preoptic area
      (Vmax: preoptic area, 290 fmol/mg tissue per h; ovarian follicles, 843 fmol/mg
      tissue per h). In intact females with developing follicles, oestradiol-17 beta
      formation was higher in the posterior hypothalamus than the preoptic area.
      Females in a later stage of reproductive development (yolked follicles) had a
      different distribution of oestrogen formation with increased aromatase activity
      in the preoptic area. Preoptic and posterior hypothalamic aromatase activity of
      females paired with males for 10 days was positively correlated (r = 0.84, P =
      0.0001; r = 0.75, P = 0.001 respectively) with ovarian development. Females with
      undeveloped ovaries which interacted with males had higher preoptic aromatase
      activity than visually isolated females with similar ovarian development,
      suggesting that behavioural stimuli have direct effects on brain aromatase
      activity which are independent of the ovary. Oestradiol benzoate treatment
      increased preoptic and posterior hypothalamic aromatase activity in intact and
      ovariectomized females, and testosterone propionate treatment increased anterior
      hypothalamic aromatase activity, but did not affect other areas, indicating that
      the distribution of induced aromatase activity is steroid-specific. Oestrogen
      treatment in ovariectomized or intact females did not replicate the maximal
      hypothalamic aromatase activity seen when the ovary contained yolked follicles.
      We conclude that brain aromatase activity is related directly to ovarian
      condition during the reproductive cycle of the female dove. As in the male,
      steroids have a role in the regulation of oestrogen formation in the female
      hypothalamus; behavioural stimuli are also likely to be involved in the control
      of the brain enzyme.

PMID- 1402545
TI  - Effect of the antiprogestin RU486 on uterine sensitivity to oxytocin in ewes in
      late pregnancy.
AB  - The effect of RU486, a synthetic progesterone receptor antagonist, on basal
      uterine prostaglandin (PG) release and release in response to oxytocin injection
      has been investigated in late-pregnant sheep (days 135-140 of gestation). Fifteen
      hours after i.m. injection of RU486 (50 mg; n = 5) or vehicle alone (n = 4),
      bolus injections of oxytocin (50, 500 and 5000 mU) were administered via a
      uterine artery ipsilateral to the pregnant uterine horn at 2-hourly intervals.
      Utero-ovarian vein concentrations of 13,14-dihydro-15-keto PGF2 alpha (PGFM) and
      PGE2 were determined before and during oxytocin stimulation. Basal concentrations
      of both PGFM and PGE2 were significantly (P < 0.001) increased in ewes 15 h after
      RU486 administration compared with ewes receiving vehicle alone. Concentrations
      of PGFM, but not PGE2, increased significantly (P < 0.001) following injection of
      each dose of oxytocin in both treated and untreated animals. The response to
      oxytocin, measured both as the area under the curve and as the peak height of
      PGFM release, was significantly (P < 0.05) greater in RU486-treated ewes. There
      was no significant effect of oxytocin on the area or peak height of PGE2 response
      in either RU486-treated or control animals. These results demonstrate that
      treatment of late-pregnant ewes with RU486 results in an increase in basal
      uterine PGFM and PGE2 as well as oxytocin-stimulated PGFM release.

PMID- 1402548
TI  - Sex hormone concentrations in blood serum from the north Atlantic fin whale
      (Balaenoptera physalus).
AB  - Blood serum concentrations of testosterone and progesterone were measured in
      postmortem samples taken at sea from 814 fin whales (Balaenoptera physalus)
      caught during the summers (June-September) of 1981-1989. The ages of 781 of these
      animals were also assessed. The testosterone concentrations in samples from 352
      males averaged 2 nmol/l; 41 samples had concentrations of 0.1 nmol/l or lower and
      34 of these came from whales aged between 2 and 14 years and showed a Gaussian
      type of age distribution with a peak number at 7 to 8 years. The mean
      testosterone concentrations in the males increased by more than fourfold between
      June and August. Serum progesterone concentrations of the 462 females fell into
      three separate groups: (1) group I with values < or = 0.1 nmol/l; (2) group II
      with intermediate values of > 0.1 nmol/l but < 10 nmol/l; (3) group III with
      values of > or = 10 nmol/l. These three groups of females seemed to consist
      respectively of young sexually immature females, mature non-pregnant females and
      pregnant females. The age distribution in the groups indicated that puberty in
      females is attained chiefly between the ages of 7 and 10. The yearly pregnancy
      rate (that percentage of all females caught and studied in a year which had
      progesterone values > or = 10 nmol/l) was between 35% and 55%, except in 1987
      when it was 67%. The yearly pregnancy rate would range from 56% to 93% if only
      mature females (i.e. those with serum progesterone > 0.1 nmol/l) were
      considered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402547
TI  - Immunological detection of the oestradiol receptor protein in cell lines derived
      from the lymphatic system and the haematopoietic system: variability of specific
      hormone binding in vitro.
AB  - Extracts of human MCF 7 mammary carcinoma cells, the human lymphoblastoid cell
      lines AEH 1 and IM 9, T-cell derived CCRF cells, HL 60 myeloic leukaemia cells
      and murine myeloma cells SP 0 and NS I were analysed for immunoreactivity with
      polyclonal goat antibodies raised against homogeneous preparations of C-terminal
      fragments (32 kDa) of porcine uterine oestradiol receptor (ER). Whole cells and
      low speed cytosols were analysed for specific oestradiol-binding activity. ERs
      were enriched from cell extracts by either fractionated ethanol precipitation (0
      25% (v/v) ethanol) and/or microscale-immunoaffinity chromatography.
      Immunoreactive proteins of identical molecular weight (approximately 65 kDa) were
      detected in all cell lines examined. Whole cell binding assays showed specific
      oestradiol-binding activity in MCF 7, IM 9 and CCRF cells. Borderline binding was
      found in HL 60 myeloid cells. No specific binding could be detected in AEH 1, NS
      I and SP 0 cells. Identical results were obtained using agar-electrophoresis
      after dextran-coated charcoal treatment. Immunoaffinity purified ERs from MCF 7,
      AEH 1 and HL 60 cells were subjected to limited proteolysis, where identical
      tryptic fragments were generated. In conclusion, we have confirmed by
      immunological methods that ERs are expressed in a variety of cell lines derived
      from the immune system and the haematopoietic system. The lack of specific
      hormone binding or very low-affinity hormone binding in some of the cells
      examined may be due to post-translational events or point mutations.

PMID- 1402549
TI  - Oestrogen enhancement of the myometrial response to exogenous parathyroid hormone
      related protein (PTHrP), and tissue localization of endogenous PTHrP and its mRNA
      in the virgin rat uterus.
AB  - Classical pharmacological studies have shown that oestrogen dominance in humans
      and other animals can increase the responsiveness of the uterus to many locally
      acting peptides. Parathyroid hormone-related protein (PTHrP) has been shown to be
      expressed in the pregnant and non-pregnant rat uterus and exogenous PTHrP is
      known to relax uterine contraction in vitro. We investigated whether oestrogen
      dominance can influence the responsiveness of the uterine horn to PTHrP, and
      further studied the localization of PTHrP mRNA and protein in the rat uterine
      horn using in-situ hybridization and immunohistochemistry. Exogenous PTHrP(1-34)
      inhibited spontaneous and electrically induced contractions in uteri isolated
      from non-cycling rats. Pretreatment of non-cycling rats with oestradiol-17 beta
      increased uterine sensitivity to PTHrP: EC50 values for inhibition of spontaneous
      contractions by PTHrP were 0.33 nmol/l, 1.1 nmol/l, 2.6 nmol/l and 7800 nmol/l in
      uteri from animals treated for 2 days with oestradiol-17 beta alone, 2 days with
      oestradiol-17 beta + 1 day progesterone, 1 day with oestradiol-17 beta alone and
      in untreated rats respectively. Similar EC50 values were obtained for
      electrically stimulated uteri. In agreement with these findings, uterine horns
      from cycling rats in pro-oestrous and oestrous phases of the cycle showed a
      higher responsiveness to PTHrP(1-34) when compared with uterine horns taken from
      rats in metoestrus and dioestrus. PTHrP mRNA and protein were detected in the
      endometrial epithelium lining of the lumen and the endometrial glands, as well as
      in the myometrium of rats which were either pretreated for 2 days with oestradiol
      17 beta or untreated. This study suggests that PTHrP may act in an autocrine
      and/or paracrine manner to modulate uterine motility and function.

PMID- 1402550
TI  - The effect of gonadotrophin surge-inhibiting factor on the self-priming action of
      gonadotrophin-releasing hormone in female rats in vitro.
AB  - The present study was designed to explore further the functional antagonism
      between gonadotrophin-releasing hormone (GnRH) and the ovarian factor,
      gonadotrophin surge-inhibiting factor (GnSIF). In all experiments, pituitary
      tissue was exposed to various amounts of GnSIF, after which the self-priming
      action of GnRH was studied. GnSIF was increased in vivo by FSH treatment and
      increased in vitro by adding various amounts of follicular fluid (FF) to cultured
      pituitary cells. Treatment with 3 or 10 IU FSH suppressed the initial LH response
      and delayed the maximally primed LH response to GnRH. Treatment with FSH was only
      effective in intact rats on days 1 and 2 of dioestrus. There was no difference in
      the rate of maximal LH release irrespective of treatment with either FSH or
      saline. Since FSH treatment was ineffective in long-term ovariectomized rats, it
      was concluded that the initial suppressive effect of FSH on LH release was
      mediated by GnSIF. Cycloheximide prevented the self-priming action of GnRH by
      inhibiting GnRH-induced protein synthesis. The initial protein synthesis
      independent GnRH-stimulated LH release, which was already suppressed by FSH
      treatment, remained suppressed in the presence of cycloheximide. Pretreatment
      with GnRH in vivo increased the protein synthesis-independent GnRH-induced LH
      release during subsequent incubation of the glands. This increase did not occur
      after FSH treatment. Pituitary cells, cultured for 20 h in medium only, failed to
      elicit the self-priming effect of GnRH. Preincubation with FF maintained the self
      priming effect. This was independent of the concomitant presence of various
      amounts of oestradiol. Preincubation with bovine FF suppressed the initial GnRH
      stimulated LH release dose-dependently. Porcine FF, human FF and testicular
      extract suppressed the release of LH in a similar way. It was concluded that
      GnSIF suppresses the initial LH response to continuous GnRH stimulation.
      Increased levels of GnSIF caused by FSH treatment also delayed the primed LH
      release. The mechanism of functional antagonism between GnSIF and GnRH could give
      rise to the occurrence of the phenomenon of GnRH self-priming.

PMID- 1402551
TI  - Effects of placing micro-implants of melatonin in the mediobasal hypothalamus and
      preoptic area on the secretion of prolactin and beta-endorphin in rams.
AB  - In a previous study, we showed that the local administration of melatonin in the
      mediobasal hypothalamus (MBH), but not the preoptic area (POA), caused a
      premature increase in the secretion of FSH and growth of the testes in sexually
      inactive Soay rams exposed to long days. To extend these observations, we have
      now measured blood concentrations of prolactin and beta-endorphin and the
      associated peripheral responses in the same animals, to establish whether the
      treatments produced multiple endocrine changes such as those which occur
      following exposure to short days. Groups of rams were initially exposed to
      alternating 16 weekly periods of long days (16 h light: 8 h darkness; 16L:8D) and
      short days (8L:16D) for at least 9 months to entrain the seasonal cycles in the
      secretion of the pituitary hormones. The treatments were started at 10 weeks
      under long days, when the animals had a physiology characteristic of the early
      summer with high blood plasma concentrations of prolactin (associated with growth
      of the summer pelage), and low concentrations of beta-endorphin (associated with
      low body weight). The animals were assigned at random to the following
      treatments: (i) micro-implants of melatonin in the MBH, (ii) microimplants of
      melatonin in the POA, (iii) empty implants in the MBH or POA to act as operated
      controls, and (iv) no surgery to act as unoperated controls (n = 12
      rams/treatment). The micro-implants consisted of 22-gauge stainless-steel needles
      with melatonin fused inside the tip. The implants were inserted bilaterally in
      the brain, and left in place for 12-14 weeks. The observations continued for a
      total of 28 weeks while the animals remained under long days. The administration
      of melatonin in the MBH induced a rapid decreased in plasma concentrations of
      prolactin while in the POA it induced a less marked but significant effect. The
      mean times to minimum concentrations of prolactin were 7.4 +/- 0.4, 17.3 +/- 2.8
      and 26.0 +/- 0.3 weeks for the MBH, POA and combined control groups respectively
      (MBH vs control, P < 0.001, POA vs control P < 0.01). In the MBH group, the
      concentrations of prolactin subsequently increased to a maximum 6 weeks after the
      end of melatonin treatment. The changes in prolactin were accompanied by changes
      in growth and moulting of the pelage; only animals in the MBH group showed a
      conspicuous moult associated with the change from low to high prolactin
      secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1402552
TI  - A simple bioassay for epidermal growth factor using pig thyrocytes.
AB  - A bioassay for epidermal growth factor (EGF) is described using an eluted stain
      assay (ESTA) of dehydrogenase activity in pig thyrocytes. Optimal responsiveness
      to EGF was obtained in confluent cultures of primary pig thyrocytes cultured with
      EGF or biological samples containing EGF for either 24 or 48 h. Dehydrogenase
      activity was determined by measuring the production and then the release of a
      coloured formazan product produced by reduction of a 3-[4,5-dimethylthiazol-2-yl]
      2,5-diphenyltetrazolium bromide substrate added to the cells. The assay responded
      equally to mouse, human and recombinant EGF and was suitable for measuring EGF
      activity in some but not all biological fluids. Specificity of detection of EGF
      activity was confirmed using antibody to EGF. The ESTA assay compared favourably
      with the radioreceptor assay for EGF in terms of sensitivity to EGF with half
      maximal activation at 0.24 +/- 0.06 nmol/l (mean +/- S.E.M., n = 22 experiments)
      for the ESTA assay and 0.60 +/- 0.13 nmol/l (n = 7 experiments) for the
      radioreceptor assay.

PMID- 1402553
TI  - The International Standard for Recombinant DNA-derived Erythropoietin:
      collaborative study of four recombinant DNA-derived erythropoietins and two
      highly purified human urinary erythropoietins.
AB  - The International Standard (IS) for Recombinant DNA-Derived (rDNA) Erythropoietin
      (EPO) (in ampoules coded 87/684) and three other rDNA EPO preparations in
      ampoules coded 87/690, 87/696 and 88/574 respectively, were compared with two
      preparations of highly purified human urinary (HU) EPO and the 2nd International
      Reference Preparation of Human Urinary Erythropoietin for Bioassay (2nd IRP) by
      26 laboratories in 11 countries using a wide range of in-vivo and in-vitro
      bioassays and immunoassays. These EPO preparations were also compared by
      electrophoresis and isoelectric focusing. Estimates of EPO content in terms of
      the 2nd IRP by all in-vivo bioassay methods gave combined unweighted geometric
      means (with 95% fiducial limits) of: 86 (75-99) IU/ampoule for the IS, 81 (70-94)
      IU/ampoule for 87/690, 58 (48-71) IU/ampoule for 87/696 and 120 (100-143)
      IU/ampoule for 88/574. Mean estimates of EPO content in terms of the 2nd IRP by
      in-vitro bioassays (except receptor assays) were larger than, and those by
      immunoassays were similar to, the mean estimates by in-vivo bioassays. The use of
      purified rDNA or HU EPO as standards in place of the 2nd IRP reduced the inter
      laboratory variability of estimates of purified EPO preparations by in-vivo and
      in-vitro bioassays and by immunoassays, and reduced the variability of overall
      mean estimates for each of these preparations between the three types of method.
      The inter-laboratory variability of immunoassay estimates of human serum EPO was
      similar whether the 2nd IRP or one of the purified EPOs was used as standard.
      Significant differences in in-vivo and in-vitro biological, immunological and
      physicochemical properties were found between these four rDNA EPO preparations
      and between them and the HU EPO in the two purified preparations and in the 2nd
      IRP. There were also differences between the immunoreactivities of the two serum
      EPO samples included in the study, and between them and the immunoreactivities of
      the purified EPOs. The differences between rDNA EPOs appeared to be related to
      differences between the cells used for their biosynthesis, but may also be the
      result of differences in purification methods and of inter-batch variations.
      Significant differences in assay specificity were observed within each of the
      three general types of method. The specificity of the in-vivo bioassays was
      influenced by the route of hormone administration. The specificities of the mouse
      spleen cell in-vitro bioassays differed from that of the mouse spleen receptor
      binding assay.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1402554
TI  - The effects of systemic insulin, insulin-like growth factor-I and growth hormone
      on bone growth and turnover in spontaneously diabetic BB rats.
AB  - Spontaneously diabetic BB rats have a markedly depressed longitudinal bone growth
      and bone formation/turnover. In this study, male diabetic BB rats were infused
      intraperitoneally or subcutaneously for 2 weeks with hormones that are believed
      to stimulate skeletal growth and/or trabecular bone formation: insulin (3 or 4
      U/day), human GH (hGH; 400 mU/day), recombinant human insulin-like growth factor
      I (rhIGF-I; 300 or 600 micrograms/day) and testosterone (80 micrograms/100 g body
      weight per day). Saline-treated diabetic BB rats had decreased plasma
      concentrations of IGF-I and osteocalcin (OC) (OC, 3.7 +/- 0.3 vs 13.1 +/- 0.8
      (S.E.M.) nmol/l in controls); bone histomorphometry showed decreased epiphyseal
      width, osteoblast surface (0.04 +/- 0.04 vs 1.5 +/- 0.3%) and osteoid surface,
      and mineral apposition rate (MAR) (1.8 +/- 0.5 vs 7.9 +/- 0.6 microns/day).
      Testosterone and hGH infusions had no effect on weight loss or on decreased
      skeletal growth and bone formation of diabetic rats, nor did they increase plasma
      IGF-I concentrations. Insulin infusions into diabetic rats resulted in
      hyperinsulinaemia and accelerated weight gain. The epiphyseal width,
      osteoblast/osteoid surfaces and OC levels of insulin-treated rats were normalized
      or stimulated well above control values (osteoblast surface, 4.3 +/- 0.8%; plasma
      OC, 16.1 +/- 1.4 nmol/l); the MAR (4.0 +/- 0.9 microns/day) was only partly
      corrected after the 2-week infusion. Infusions of rhIGF-I into diabetic rats
      doubled but did not restore plasma IGF-I levels to normal; weight gain, however,
      was similar to that in control rats. IGF-I treatment had no effect on epiphyseal
      width, osteoblast/osteoid surfaces and OC concentrations, but improved the
      decreased MAR (4.6 +/- 1.2 microns/day).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402555
TI  - Primiparous rhesus monkey mothers are more sensitive to the nursing-induced
      inhibition of LH and ovarian steroid secretion.
AB  - The duration of lactational infertility is prolonged significantly in adolescent,
      primiparous rhesus monkey (Macaca mulatta) mothers compared with adult,
      multiparous mothers. The present study examined the hypothesis that this
      parity/age difference in lactational infertility is due to a difference in the
      physiological responsiveness to nursing behaviour between adolescent and fully
      adult mothers and is not a consequence of differences in nursing behaviour, per
      se. At 22 weeks postpartum, mother-infant pairs were randomly assigned to one of
      four conditions: primiparous, nursing restricted (PR; n = 9); primiparous,
      nursing unrestricted (PU; n = 11); multiparous, nursing restricted (MR; n = 12);
      and multiparous, nursing unrestricted (MU; n = 8). Nursing was restricted for a 2
      week period by mothers wearing a primate vest which prevented suckling behaviour
      but allowed infants to interact with their mothers. Nursing restriction resulted
      in a significant increase in serum oestradiol concentrations in both PR and MR
      mothers. Although nursing bout frequencies and durations were similar between PU
      and MU mothers, serum oestradiol also rose in MU mothers but remained suppressed
      in PU mothers. Once the nursing manipulation period ended and all mothers were
      allowed to nurse ad libitum, serum oestradiol concentrations continued to rise in
      all but the PU mothers. This brief interruption of nursing at 22 weeks postpartum
      advanced the subsequent timing of the first postpartum ovulation in MR and PR
      mothers relative to that of PU mothers. Again, despite similarities in nursing
      behaviour, the occurrence of first ovulation was also advanced in MU mothers
      compared with PU mothers. Just prior to the first postpartum ovulation, females
      were randomly assigned to one of four treatment groups to determine the effects
      of nursing behaviour on the hormonal parameters of the luteal phase: primiparous,
      nursing restricted (PRL; n = 9); primiparous, nursing unrestricted (PUL; n = 11);
      multiparous, nursing restricted (MRL; n = 10); and multiparous, nursing
      unrestricted (MUL; n = 10). Nursing restriction significantly elevated serum
      progesterone concentrations in PRL females compared with other mothers. Serum
      concentrations of oestradiol were higher in PRL, MRL and MUL mothers relative to
      PUL females. Again, this difference in oestradiol between PUL and MUL mothers
      occurred despite similarities in nursing behaviour. These data suggest that
      parity/age differences in the period of lactational infertility are not due to
      differences in nursing behaviour but rather to an increased sensitivity to the
      inhibitory aspects of the suckling stimulus in adolescent primiparous
      mothers.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1402556
TI  - In vitro intracanal temperatures produced during warm lateral condensation of
      Gutta-percha.
AB  - In vitro intracanal temperatures produced during the war lateral condensation of
      gutta-percha were measured using a computerized recording system that allowed
      repeated obturations of a root canal model. The obturations were performed using
      a Touch 'n Heat unit. Temperatures were recorded to an accuracy of a hundredth
      degree centigrade by 16 intracanal themocouples connected to the computerized
      measurement system. The highest intracanal temperature recorded was 114.51
      degrees C at a power setting of 6, while the mean intracanal temperature increase
      above the average room temperature ranged from 8.18 to 65.05 degrees C. In
      addition, the spreader was not uniformly heated to the same temperature
      throughout its entire length. The hottest point on the spreader was located 5 mm
      from the tip.

PMID- 1402557
TI  - Comparison of conventional root canal obturation techniques with Thermafil
      obturators.
AB  - This study compared microleakage of Thermafil Obturators to the single cone
      technique in Lexan blocks simulating root canals (n = 20) stained with Prussian
      blue dye. The microleakage of Thermafil and laterally condensed extracted human
      teeth was also investigated after the teeth were stained with India ink or
      Prussian blue dye over 1- or 2-wk dye immersion periods. In Lexan blocks there
      was no statistical difference in mean leakage between the single cone technique
      and Thermafil. Teeth with Thermafil Obturators exhibited greater leakage than
      those with the lateral condensation. Greater leakage was also seen where India
      ink was used. Dye immersion time did not have a significant influence on leakage
      scores. The combination of India ink with Thermafil demonstrated the greatest
      average leakage. This study demonstrated that Lexan canal simulating blocks do
      not mimic extracted human teeth for evaluating microleakage.

PMID- 1402558
TI  - Physical dimensions, torsional performance, and metallurgical properties of
      rotary endodontic instruments. 3. Peeso drills.
AB  - A laboratory study was performed on Peeso drills to determine their physical
      dimensions, torsional performance, and metallurgical properties. Samples were
      measured from each of sizes #1 to #6 of Peeso drills (type P) and sizes #009 to
      #023 of Peeso drills (type B-1) from the two manufacturers that distribute these
      instruments in the United States. They were also tested in clockwise and
      counterclockwise torsion using a digital torque meter instrument. It was not
      possible to evaluate completely some type P drills of size #4 and larger or type
      B-1 drills of size #016 and larger because the torsional moments exceeded the
      capacity of the test instrument. Scanning electron microscopic examination
      confirmed visual observations that the stainless steel Peeso drills exhibited
      ductile torsional fracture, in contrast to the carbon steel Peeso drills which
      fractured in a relatively brittle manner. The carbon steel Peeso drills exhibited
      a much greater tendency for torsional fractures in the bur head, along with
      considerably smaller values of angular deflection at separation compared to the
      stainless steel Peeso drills. This study is part of a continuing investigation to
      establish standards for all rotary endodontic instruments.

PMID- 1402559
TI  - A radiographic comparison of two root canal instrumentation techniques.
AB  - The ability of two instrumentation techniques to negotiate and enlarge small
      curved canals was com-compared radiographically. Fifty canals in extracted human
      molar teeth were instrumented by the progressive enlargement (PE) technique, a
      form of step-back preparation using standard K files, or by the balanced force
      (BF) technique using K files whose tips had been specially modified. By using
      drawings and projected radiographic images of the files, the position of the
      largest file used in the apical preparation, #30 or #35 for the PE technique and
      #45 for the BF technique, was compared with the position of a small file placed
      in the canal before instrumentation. The PE and BF techniques were equally
      capable of instrumenting small curved canals to their respective largest apical
      preparation sizes. However, at sizes equivalent to the largest apical preparation
      sizes used in the PE technique, the BF technique produced significantly less
      deviation from the center of the original canal.

PMID- 1402560
TI  - Comparison of apical leakage in teeth obturated with a polyamide varnish or zinc
      oxide and eugenol cement using lateral condensation.
AB  - The sealing ability of copal varnish has been investigated when used as an
      adjunct in restorative procedures, retrofilling procedures, and dontic obturation
      procedures. Barrier, a polyamide-type polymer cavity varnish, has been compared
      with copal varnishes in restorative dentistry. This investigation compared the
      apical sealing properties of a zinc oxide and eugenol sealer (Roth) with a
      polyamide varnish (Barrier). Twenty-four teeth were instrumented and divided into
      two groups, one obturated with gutta-percha and Roth sealer and one with gutta
      percha and Barrier, using submersion in methylene blue dye to demonstrate apical
      leakage. Roth sealer exhibited less dye penetration than Barrier when used as an
      endodontic sealant (p < 0.02).

PMID- 1402561
TI  - Antibodies in normal and diseased pulps reactive with microorganisms isolated
      from deep caries.
AB  - Immunoglobulin molecules in the supernatant fluids (SF) from pulpal explant
      cultures have been observed to react with microorganisms implicated in infections
      of root canals. In this study, the reactivity of immunoglobulin molecules in the
      SF from normal and irreversible pulpitis pulps to six strains of predominant
      microorganisms isolated from the immediate layer of carious lesions above the
      pulps used for explant cultures was investigated using an enzyme-linked
      immunosorbent assay. Two ATCC strains of Eubacterium were also included in this
      assay. Specific antibodies to Lactobacillus casei subsp. casei, Lactobacillus
      casei subsp. rhamnosus, Lactobacillus acidophilus (I), (II), Streptococcus
      mutans, Bacteroides intermedius, Eubacterium brachy, and Eubacterium
      alactolyticum in the SF from the normal and irreversible pulpitis tissues were
      observed with a large variation of antibody levels in both groups.
      Immunodiffusion assays of the SF revealed that IgG was the major class of
      immunoglobulin in the normal as well as the irreversible groups. The presence of
      natural antibodies in the normal pulps suggested a possible protective role of
      antibodies during the invasive process of caries.

PMID- 1402562
TI  - Effect of noncutting tipped instruments on the quality of root canal preparation
      using a modified double-flared technique.
AB  - Fifty-one extracted human first molar teeth with intact crowns and mature root
      apices were divided into three groups. Root curvature was determined. One of the
      root canals in the mesial root of lower molars, or the mesiobuccal root in
      maxillary molars, was prepared in one of three ways. In group 1 the root canals
      were instrumented using a modified double-flared technique with noncutting tipped
      files (Flex R); in group 2 the same files were used with a step-back technique.
      Group 3 was prepared with conventionally tipped files (K-Flex) using the step
      back technique. A low viscosity polyvinyl siloxane impression material was
      injected into the prepared root canals and the specimens were decalcified,
      dehydrated, and cleared. The preparation was evaluated subjectively according to
      various desirable or undesirable criteria. A rating for overall quality of
      preparation was given. Statistical analysis showed that the teeth in group 1 had
      better overall preparation than those in group 3 (p < 0.05). There were no other
      statistically significant differences between the groups. The mean time required
      for each preparation technique was not statistically significantly different (p >
      0.1). The use of a modified double-flared technique with non-cutting tipped files
      was shown to be an effective method for the preparation of curved root canals.

PMID- 1402563
TI  - Use of dental instruments for bridging during electric pulp testing.
AB  - It has been suggested that dental instruments can be used as bridging instruments
      to facilitate electric pulp testing of teeth with extensive restorations. This
      study reports a clinical investigation to evaluate the effectiveness of this
      procedure. One hundred seventeen vital teeth in 20 volunteers were tested. Ten
      endodontically treated teeth functioned as controls. Following appropriate
      isolation and asepsis technique, baseline recordings of the threshold response
      with the electric pulp tester were taken. With the use of dental explorers and
      endodontic files to bridge between the probe tip and the tooth surface,
      recordings were made of the threshold responses. Findings indicate that
      electrically conductive dental instruments can be reliably used as bridging
      instruments with the electric pulp tester.

PMID- 1402564
TI  - Root end isolation for retrograde fillings.
AB  - Isolation and moisture control of the root end of a tooth with a large periapical
      lesion is normally accomplished with the aid of bone wax, cotton pellets, or
      sterile gauze saturated with a suitable hemostatic agent. An alternative
      procedure, a simple and effective rubber dam technique, is presented
      demonstrating isolation of an apex before reverse filling.

PMID- 1402565
TI  - Thermal analysis of commercial Gutta-percha using differential scanning
      calorimeter and dynamic mechanical thermal analysis.
AB  - Gutta-percha is the most widespread root canal filling material and knowledge of
      its chemical and thermomechanical properties is of a great interest to its use in
      clinical dentistry. In the present investigation, the results from differential
      scanning calorimeter were compared with those obtained by dynamic mechanical
      thermal analysis. A significant correlation was established between these results
      and the chemical composition of six different commercial samples of gutta-percha.

PMID- 1402567
TI  - Autonomic nerve endings in the odontoblast/predentin border and predentin of the
      canine teeth of dogs.
AB  - Autonomic nerve endings in the odontoblast/predentin border and the predentin
      were observed by electron microscopy in the canine teeth of dogs. Adrenergic
      nerve endings with a number of very electron-dense granular vesicles and a
      minority of agranular vesicles of different sizes were clearly observed, but seen
      rarely, at the odontoblast/predentin border, in the predentin adjacent to the
      odontoblast processes, and as free endings in the middle part of the predentin.
      Cholinergic nerve endings were also observed with a number of agranular vesicles
      of different sizes without any visible exocytosis, in the odontoblast/predentin
      border, and in the predentin. Near the areas of collagen formation, extensive
      exocytosis of granular vesicles of different sizes was observed in adrenergic
      nerve endings located as free nerve endings in the predentin.

PMID- 1402566
TI  - Effect of intracoronal bleaching on external cervical root resorption.
AB  - The purpose of this study was to examine histologically and radiographically the
      effect of a bleaching agent, a mixture of sodium perborate and superoxol (30%
      hydrogen peroxide), without a heat source on the cervical root surface and
      periodontal tissue of endodontically treated teeth of dogs. Endodontic treatment
      was performed on anterior teeth of dogs. The endodontically treated teeth were
      then divided into two groups. One group received walking bleach procedures, while
      the other group did not. The animals were killed at intervals of 1 and 3 months
      after bleaching for histological and radiographic examination. External cervical
      root resorption was only observed in bleached teeth at 3-month but not at 1-month
      observation.

PMID- 1402568
TI  - A bacteriological and histological evaluation of 58 periapical lesions.
AB  - Periapical tissue from 58 cases requiring periapical surgery was examined
      histologically and cultured for the presence of microbes. Twenty-nine had a
      possible oral cavity communication and 29 did not. Approximately one-half of each
      biopsy was submitted for culture while the other portion was examined
      histologically. Cultures were positive for the presence of bacteria in 51 of 58
      cases while bacteria were seen histologically in only 8 of 58 cases. A total of
      50 different species of bacteria were isolated from the 58 cultures of periapical
      tissue. Of 133 isolates, 87 were strict anaerobes, 37 were facultative anaerobes,
      and 9 were aerobes. Bacteroides species were found in 17 cultures, always with
      additional bacteria. Seventeen of 58 biopsies contained foreign particulate
      matter thought to be root canal sealer. Bacteria were found in periapical
      granulomas, radicular cysts, and a periapical abscess. According to our data,
      bacteria, foreign material, missed canals, vertical root fractures, and
      periodontal disease may all contribute to the chronic, non-healing periradicular
      lesion.

PMID- 1402569
TI  - A comparison of apical seal: chloroform versus halothane-dipped gutta-percha
      cones.
AB  - A dye penetration study was done to compare apical leakage among three groups of
      extracted teeth obturated with a lateral condensation technique. In one group the
      master gutta-percha cones were customized in the apical portion of the canals
      after being dipped in chloroform. A second group used halothane as the
      customizing agent. No dip was used in the third group, and all three were then
      laterally condensed. The teeth were cleared and dye penetration was measured.
      Statistical analysis using a Kruskal-Wallis one-way analysis of variance of the
      data showed no significant difference among the groups at the p < 0.05 level.

PMID- 1402570
TI  - Anatomical relationship of the mandibular canal to its surrounding structures in
      mature mandibles.
AB  - A lack of agreement exists in the literature regarding the anatomical
      relationship of the mandibular canal to its surrounding structures such as the
      root apices. The purpose of this investigation was to study the spatial
      relationship of the mandibular canal to the posterior teeth in dried human
      mandibles. Twenty-two mature dried mandibles were sectioned through the root
      apices of the first and second premolars and molars. Second premolars and second
      molars had the closest distances to the canal with a mean of 4.7 mm and 3.7 mm,
      respectively. With a mean of 6.9 mm, the apices of the mesial roots of the first
      molars were farthest from the canal. The canal pathway in mature mandibles
      followed in S-shaped curve in 31% of the cases. In 41% of the cases it was
      located lingual (19%), buccal (17%), or directly inferior (5%) to the apices of
      the posterior teeth. In 28% of the cases the canal could not be identified
      clearly in the second premolar and first molar regions. In a typical S-shaped
      configuration the canal was located buccal to the distal root of the second
      molar, crossed to the lingual below the second molar mesial root, ran lingual to
      the first molar, and crossed back to the buccal apical to the apex of the second
      premolar. Based on our results it appears that the mandibular second premolar and
      second molar are the most likely teeth to be involved in accidental damage to the
      mandibular canal during root canal therapy.

PMID- 1402571
TI  - Endodontic interappointment flare-ups: a prospective study of incidence and
      related factors.
AB  - Severe pain and/or swelling following a root canal treatment appointment are
      serious sequelae. Information varies or is incomplete as to the incidence of
      these conditions and related factors. In this study, data were collected at root
      canal treatment appointments on demographics, pulp/periapical diagnoses,
      presenting symptoms, treatment procedures, and number of appointments. Patients
      that then experienced a flare-up (a severe problem requiring an unscheduled visit
      and treatment) had the correlating factors examined. Statistical determinations
      were by chi-square analysis with significance at 0.05 or less. Nine hundred forty
      six visits resulted in an incidence of 3.17% flare-ups. Flare-ups were positively
      correlated with more severe presenting symptoms, pulp necrosis with painful
      apical pathosis, and patients on analgesics. Fewer flare-ups occurred in
      undergraduate patients and following obturation procedures. There was no
      correlation between patient demographics or systemic conditions, number of
      appointments, treatment procedures, or taking antibiotics.

PMID- 1402572
TI  - Healing of a sinus tract of periodontal origin.
AB  - A sinus tract adjacent to teeth is usually considered to be of endodontic origin
      and root canal therapy is the primary treatment to achieve healing. A case of a
      sinus tract is presented in which a suspected endodontic-periodontic lesion was
      successfully treated by periodontal therapy alone. The sinus tract healed and the
      radiograph showed bony repair.

PMID- 1402573
TI  - Zebra X. Part 2. Central ossifying fibroma.

PMID- 1402574
TI  - Effects of moisture content and endodontic treatment on some mechanical
      properties of human dentin.
AB  - The objective of this study was to determine whether significant differences
      exist between the mechanical properties of human dentin from treated pulpless
      teeth and dentin from normal vital teeth. Dentin specimens (n = 262) were
      obtained from 54 freshly extracted normal vital human teeth and 24 treated human
      pulpless teeth. These specimens were subjected to different experimental
      conditions (wet, air dried, desiccated, and rehydrated). Compression, indirect
      tensile, and impact tests were conducted to measure the mechanical properties of
      those specimens. All data obtained were analyzed with t tests. The results showed
      that the dehydration of dentin increases the Young's modulus, proportional limit
      (in compression), and especially the ultimate strength (in both compression and
      tension). Substantial dehydration changes the fracture characteristics of dentin
      specimens under static compressive and indirect tensile loadings. The
      measurements of impact-breaking energies of desiccated dentin were not found to
      be significantly decreased. The compressive and tensile strengths of dentin from
      treated pulpless teeth obtained in this study do not appear to be significantly
      different from those of normal dentin (p > 0.05), while the mean values of
      Young's modulus and proportional limit in compression tests appear to be lower.
      Fifty percent of the dentin specimens from treated pulpless teeth exhibit greater
      plastic deformation than normal dentin in compression. The results of this study
      do not support the theory that dehydration after endodontic treatment per se
      weakens dentin structure in terms of compressive and tensile strengths. Other
      mechanical properties of treated pulpless teeth, however, may not be the same as
      those of normal vital teeth.

PMID- 1402575
TI  - Histological evaluation of the presence of bacteria in induced periapical lesions
      in monkeys.
AB  - In endodontic periapical lesions, both presence and location of bacteria are
      controversial. Various experimental techniques have produced differing results
      perhaps related to potential artifacts such as contamination during specimen
      recovery. Our objective was to examine for bacteria in uncontaminated,
      undisturbed periapical lesions in an animal model. Pulp necrosis was induced by
      exposing molars in nonhuman primates and closing the exposure after 1 week with
      amalgam. Lesions developed at 18 apices. After 7 months, block sections including
      tooth and surrounding tissues were removed, processed histologically, and Gram
      stained. Bacteria, primarily Gram positive, were consistently identified in
      necrotic tissue in canals. Two canals demonstrated bacterial masses to the apical
      foramen. No bacterial colonies, only intracellular microorganisms, were seen
      periapically. Inflammatory lesions seemed to resist the spread of bacteria,
      confining them to the canal space. Bacterial masses at the apical foramen could
      contaminate periapical tissues during surgery or extraction and give a false
      positive upon microbiological sampling.

PMID- 1402576
TI  - Torsional properties of the Canal Master instrument.
AB  - The torsional properties of a new type of endodontic hand instrument, the Canal
      Master, were compared with conventional machined K-type endodontic files. Sizes
      20 through 50 were tested in clockwise (CW) and counterclockwise (CCW)
      directions. Canal Master instruments exhibited significantly less torque at yield
      and at failure in both the CW and CCW directions. Rotation at failure was
      significantly greater for the Canal Master instruments in both CW and CCW
      directions. There was no significant difference in either torque or the amount of
      rotation for the Canal Master instruments when comparing CW versus CCW rotation.
      There was no clinically visible evidence of deformation of the Canal Master
      instruments prior to torsional failure.

PMID- 1402577
TI  - Response of pulpal blood flow to intra-arterial infusion of endothelin.
AB  - Laser Doppler flowmetry was used to determine the effect of the vasoconstrictor
      endothelin 1 (ET-1) on the pulpal blood flow of intact dogs' teeth during
      mandibular arterial infusion. ET-1 produced a profound decrease in pulpal blood
      flow of a relatively long duration at lower doses than similar infusions of
      norepinephrine. The decrease in pulpal blood flow in response to ET-1 was
      partially attenuated by the calcium channel blocker nifedipine. These findings
      demonstrate the presence of receptors for ET-1 in the microvasculature of the
      dental pulp and suggests that ET-1 may function in the local control of the
      pulpal microcirculation.

PMID- 1402578
TI  - Effect of precurving on the performance of endosonic K files.
AB  - This study compared the performance of precurved and straight endosonic files.
      Size 15, 20, and 25 endosonic K files were precurved to different degrees (20 to
      90 degrees) and the resultant oscillatory pattern showed no significant
      difference compared with corresponding straight files. Endovue blocks were
      prepared with either a #15, 20, or 25 endosonic file which was either straight or
      precurved. Those blocks prepared with precurved files had a continuous taper
      while blocks prepared with straight files had constrictions along their lengths.
      Finally, a curved root of a human natural tooth had windows prepared along its
      length so that the oscillatory pattern of the file could be observed. The
      precurved file oscillated more freely than a straight file as observed by the
      presence of antinodes along the file and the accumulation of dentin chips within
      the canal. The results of this study suggest that it is advantageous to precurve
      endosonic files before using them in curved canals.

PMID- 1402579
TI  - Magnetic resonance imaging of human teeth.
AB  - There is a need in clinical dentistry for improved diagnostic methods for an
      accurate evaluation of pulp tissue pathosis. The purpose of this investigation
      was to attempt to image extracted human teeth with the aim of establishing the
      possible future application of magnetic resonance imaging in the diagnosis of
      pulpal pathosis. The results of this pilot study demonstrate that, in the in
      vitro setting, the outline of the tooth and pulp chamber can be imaged with a
      high degree of accuracy, and detailed images of the periodontal membrane and
      gross pulpal anatomy can be obtained. There were obvious differences in the
      signals given off by different locations within these teeth, and the images of
      the dental pulp tissue were detailed enough to suggest the possible correlation
      with histology. The high (9.4 T) field strengths used in this study demonstrate
      the in vitro application of this technology and the future possibilities for
      diagnosis of periodontal and odontogenic problems are significant.

PMID- 1402581
TI  - Reference block for auxiliary cones.
AB  - A technique is described for fabricating a reference block which will allow the
      practitioner to select the accessory cones most correctly corresponding to the
      spreader used. The technique utilizes materials common to the dental office and
      is simple enough to allow fabrication of a new block whenever the obturation
      instruments or materials are changed.

PMID- 1402580
TI  - Endodontic stabilizers.
AB  - With the recent influx of osseointegrated endosseous implants in dentistry,
      attention has been drawn away from using endodontic stabilizers as a means of
      stabilizing and retaining teeth. It is our opinion that endodontic stabilizers
      should be considered in the treatment planning of seemingly nonretainable teeth.
      They are biocompatible and have the additional advantage of maintaining the
      periodontal membrane attachment of the remaining tooth. Extraction and subsequent
      replacement with osseointegrated implants should only be considered after all
      other means of retaining the natural tooth have been fully explored. Selective
      case studies from various areas of the dentition demonstrate the broad
      applicability of stabilizers. A technique is presented for the use of endodontic
      stabilizers.

PMID- 1402582
TI  - Effects of CO2 laser energy on dentin permeability.
AB  - The effect of a CO2 laser on the structure and permeability of smear layer
      covered human dentin was evaluated in vitro. Three different energy levels were
      used (11, 113, and 566 J/cm2). The lowest exposure to the laser energy increased
      dentin permeability, measured as a hydraulic conductance, due to partial measured
      as a hydraulic conductance, due to partial loss of the superficial smear layer
      and smear plugs. The intermediate energy level also increased dentin permeability
      by crater formation, making the dentin thinner. The lack of uniform glazing of
      the surface of the crater, leaving its surface porous and in communication with
      the underlying dentinal tubules also contributed to the increase in dentin
      permeability seen with the intermediate laser energy. The highest laser energy
      produced complete glazing of the crater surfaces and sealed the dentinal tubules
      beneath the crater. However, it also completely removed the smear layer in a halo
      zone about 100-microns wide around each crater which increased the permeability
      of the pericrater dentin at the same time it decreased the permeability of the
      dentin within the crater. The combined use of scanning electron microscopy and
      permeability measurements provides important complementary information that is
      essential in evaluating the effects of lasers on dentin.

PMID- 1402583
TI  - Thermomechanical analysis of dental gutta-percha.
AB  - Samples of three common commercial gutta-percha endodontic filling points
      (Hygienic, Mynol, and Maillefer Pink) and a sample of natural gutta-percha were
      submitted to thermomechanical analysis under pressures ranging from 0.01 to 0.2
      N. Samples of Mynol and Maillefer filling points were thermally treated and then
      submitted to thermomechanical analysis in parallel with differential scanning
      calorimetric analysis. The results show that thermomechanical analysis gives
      results distinct from those obtained by classic dilatometry and that it is a
      technique well suited to the study of the thermoplastic properties of gutta
      percha. An analysis of the results shows that the amount of the inorganic
      component used in a commercially available endodontic point has a strong
      influence on its thermomechanical properties. Thermodynamical properties and the
      "thermal history" of the gutta-percha are also important. Both temperature and
      force should be controlled in order to assess the thermomechanical properties of
      endodontic filling points, while the latter have not yet been codified in
      clinical procedures.

PMID- 1402584
TI  - The mental foramen: 2. Radiographic position in relation to the mandibular second
      premolar.
AB  - Seventy-five adult human mandibles were radiographed with a paralleling technique
      to determine the ability to visualize the mental foramen as well as its size and
      position. The foramen was seen on 75% of the horizontal periapical radiographs
      examined. When the foramen was not visualized, is was usually below the inferior
      edge of the film. The radiographic size of the foramen was smaller than the
      anatomical size previously reported. The position of the mental foramen was
      usually mesial and below the radiographic apex of the second premolar.

PMID- 1402585
TI  - Assessment of external root resorption using digital subtraction radiography.
AB  - Digital subtraction radiography was investigated for its capability to detect and
      quantify experimentally produced external root resorptive defects in teeth. Using
      a long source to object X-ray technique and E-speed film, serial radiographs of
      teeth with artificial lesions in a dry human skull (soft tissue simulated) were
      obtained. Receiver operating characteristic analysis was used to evaluate the
      diagnostic performance for each imaging system (conventional versus subtraction).
      To explore the quantitative assessment potential of digital subtraction
      radiography, images were produced after sequential demineralization by HCl. The
      acid solution was analyzed for calcium concentration by atomic absorption
      spectrophotometry. Three-dimensional histogram quantification for each subtracted
      image was performed. In overall performance for detecting experimentally produced
      external root resorption, digital subtraction radiography was found to be
      significantly superior to conventional radiography. In addition, digital
      subtraction radiography can provide quantification of experimentally produced
      external root resorptive defects.

PMID- 1402586
TI  - Evaluation of Thermafil obturation of curved canals prepared by the Canal Master
      U system.
AB  - A dye penetration study was performed to compare the apical seals obtained with
      laterally condensed gutta-percha and Thermafil. The sample group contained 40
      teeth with curved canals which had been prepared with the Canal Master-U System.
      Canal curvature was measured and the teeth were decalcified, cleared, and linear
      dye penetration was measured. Thermafil had statistically more linear leakage as
      verified by a Wilcoxon test (p < 0.001). Thermafil also had greater variability
      in the apical seal than did laterally condensed gutta-percha as verified by an F
      test (p < 0.001). A Spearman correlation analysis (p > 0.05) showed that there
      was no correlation between root curvature and linear dye penetration.

PMID- 1402587
TI  - Effect of bleaching agents on inorganic components of human dentin and cementum.
AB  - The effect of bleaching agents on the inorganic composition of human dentin and
      cementum was examined. Intact teeth were crushed, pulverized, and separated to
      dentin and cementum powders. The pulverized tissues were exposed to treatments
      with 30% H2O2, 3% H2O2, 2% sodium perborate in 30% H2O2, 2% sodium perborate in
      3% H2O2, and 2% sodium perborate in bidistilled water for periods of 15 min and
      1, 24, and 72 h. The degree of dissolution and the percentage of inorganic
      material for both dentin and cementum were measured. Thirty percent H2O2 and 2%
      sodium perborate in 30% H2O2 treatments significantly increased the solubility of
      dentin and cementum. The degree of dissolutions and the percentage of inorganic
      material remaining in the undissolved dentin and cementum increased with time
      progression. The greatest increase occurred with 30% H2O2 and 2% sodium perborate
      in 30% H2O2 after 24- and 72-h treatments. It is concluded that 30% hydrogen
      peroxide treatment may cause alteration in the chemical structure of the dentin
      and cementum making them more susceptible to degradation.

PMID- 1402588
TI  - A three-dimensional study of canal curvatures in the mesial roots of mandibular
      molars.
AB  - The degree and configuration of canal curvature was studied in the mesial roots
      of 100 randomly selected mandibular first and second molars. The teeth were
      radiographed in buccolingual (clinical) and mesiodistal (proximal) directions
      with #8 K files in place. One hundred percent of the specimens demonstrated
      curvature in both views. No correlation in degree of curvature was found to exist
      between the clinical and proximal views. Secondary curvature, in a direction
      opposite to that of the principle curve, was seen more frequently in the proximal
      view. In the proximal view, canals exhibited greater mean curvature than in the
      clinical view 38% of the time. Weine type II morphology (two canals, one foramen)
      demonstrated the greatest range in canal curvature when viewed from the proximal.
      Coronal flaring with Canal Master rotary instruments to a level just coronal to
      the curve significantly reduced the severity of curvatures in both views for most
      cases.

PMID- 1402589
TI  - Chloroform in the endodontic operatory.
AB  - This article reviews the role chloroform has played in dentistry and describes an
      occupational health clinical investigation into the possible hazards of
      chloroform use in the operatory. Due to a Food and Drug Administration ban on
      drugs and cosmetics containing chloroform, there has been some confusion as to
      whether the use of chloroform in the practice of dentistry is considered unsafe
      or has been prohibited. Utilizing common endodontic treatment methods employing
      chloroform, this study reports no negative health effects to the dentist or
      assistant and air vapor levels well below Occupational Health and Safety
      Administration mandated maximum levels. The report concludes that, with careful
      and controlled use, chloroform can be a useful adjunct in the practice of
      dentistry. The Food and Drug Administration has no jurisdiction over a dentist's
      use of chloroform in clinical practice and has not proven that chloroform is a
      human carcinogen.

PMID- 1402590
TI  - Odontogenic cutaneous sinus tract.
AB  - Patients with odontogenic cutaneous sinus tracts usually seek treatment from a
      physician instead of a dentist and the etiology is frequently misdiagnosed. This
      case report describes a patient who sought treatment from a dentist because of a
      history of a previous cutaneous swelling on the ipsilateral side of his cheek.
      The etiology of the present swelling was a carious tooth. The patient was treated
      concurrently with both nonsurgical endodontic therapy and transcutaneous drainage
      by aspiration. This method of drainage precluded possible spontaneous drainage
      and avoided damage to proximal anatomical structures which may have occurred if
      an incision had been used.

PMID- 1402591
TI  - Penetration of the pulp chamber by carbamide peroxide bleaching agents.
AB  - Hydrogen peroxide readily penetrates the pulp chamber of freshly extracted teeth.
      This study was undertaken to determine whether carbamide peroxide also penetrates
      the pulp chamber. Freshly extracted teeth were sectioned 2 to 3 mm apical to the
      cementoenamel junction and the coronal pulpal tissue was removed. Acetate buffer
      was placed in the pulp chamber to absorb and stabilize any peroxide that might
      penetrate. The coronal portion of each tooth was immersed in either carbamide
      peroxide gel or gelled hydrogen peroxide at various concentrations for 15 min at
      37 degrees C. The buffer was removed, leukocrystal violet was added, and the
      optical density of the resulting blue solution was determined
      spectrophotometrically. Amounts of peroxide found in the pulp chamber after 15
      min ranged from 3.3 +/- 0.38 micrograms for the 10% sample to 40.4 +/- 3.51
      micrograms for the 30% sample.

PMID- 1402592
TI  - Master cone apical behavior under in vitro compaction.
AB  - This study first evaluated the fitting of two brands of gutta-percha points 0.5
      and 1.0 mm short of the apical end of an artificial canal. Photographs were taken
      before and after vertical or lateral compaction and measurements were made. Warm
      gutta-percha compaction was associated with greater apical cone movement than
      lateral condensation. Total apical cone movement was not related to the distance
      the master cone was initially adapted from the apical opening.

PMID- 1402593
TI  - Sealing ability of Thermafil with and without sealer.
AB  - The purpose of this study was to evaluate the apical sealing ability of root
      canals filled using three obturating techniques. Sixteen maxillary first molars
      were obturated with Thermafil, 16 with Thermafil and a ZOE sealer, and 16 with
      laterally condensed gutta-percha. Two canal instrumentation methods were used,
      conventional step-back preparation with K-Flex files and traditional
      instrumentation combining reaming with reamers and filing with K-Flex files.
      Following obturation, the teeth were prepared for evaluation of the seal using
      India ink and a Profile Projector. The depth of penetration of the dye was
      statistically evaluated for each of the three roots with an analysis of variance.
      For sealing ability, there was no significant difference at the p < 0.05 level
      between the conventional step-back preparation and the traditional
      instrumentation technique. However, a significant difference was present at the p
      < 0.05 level for the obturation techniques. The mean linear dye penetration for
      the Thermafil technique was greater than that for lateral condensation.

PMID- 1402594
TI  - In vivo and in vitro glycosaminoglycans from human dental pulp.
AB  - A qualitative assessment was made of the type of glycosaminoglycans (GAG) present
      in normal human dental pulp using electrophoresis on cellulose-acetate plates. A
      comparison was also made between the GAG derived directly from the dental pulp
      (in vivo) and those derived from cultured pulp fibroblasts from the same
      individual (in vitro). The results of this study showed four main types of GAG in
      normal human dental pulp tissue, which were dermatan sulfate, heparan sulfate,
      hyaluronic acid, and chondroitin sulfate. GAG synthesis from cultured pulp
      fibroblasts in vitro was different from the GAG present in the dental pulp (in
      vivo). Extracellular GAG, as well as pericellular GAG consisted of dermatan
      sulfate, hyaluronic acid, chondroitin sulfate, and heparin. Cellular GAG,
      however, contained only dermatan sulfate, hyaluronic acid, and chondroitin
      sulfate. There was no difference in type of GAG from the second and fourth
      passaged pulp fibroblasts.

PMID- 1402595
TI  - Are endodontically treated teeth more brittle?
AB  - This study compared biomechanical properties (punch shear strength, toughness,
      hardness, and load to fracture) of 23 endodontically treated teeth (mean time
      since endodontic treatment: 10.1 yr) and their contralateral vital pairs.
      Analyses using paired t tests revealed no significant differences in punch shear
      strength, toughness, and load to fracture between the two groups. Vital dentin
      was 3.5% harder than dentin from contralateral endodontically treated teeth (p =
      0.002). The similarity between the biomechanical properties of endodontically
      treated teeth and their contralateral vital pairs indicates that teeth do not
      become more brittle following endodontic treatment. Other factors may be more
      critical to failure of endodontically treated teeth.

PMID- 1402596
TI  - Canal Master files: scanning electron microscopic evaluation of new instruments
      and their wear with clinical usage.
AB  - Canal Master instruments have a short, fluted cutting area and a small flexible
      shaft; they may be predisposed to rapid wear and breakage. This study examined
      new and used files as to tip, flute, and shaft design when new and with
      increasing time of canal preparation. One hundred files prepared 140 curved
      canals. Sizes #20, #40, and #60 files were examined unused and after 1, 3, 5, and
      7 min of use. Evaluation was for uniformity when new and for deterioration and
      breakage with usage. The smaller sizes (#20 and #40) had some inconsistencies
      when new and were most predisposed to wear and breakage with time. Findings
      suggest that smaller files could have had improved quality control by the
      manufacturer. Also, they should be used with caution and discarded after short
      times of use in small, curved canals. This should minimize instrument separation
      and maximize cutting efficiency.

PMID- 1402597
TI  - An evaluation of the Thermafil endodontic obturation technique.
AB  - The purpose of this study was to evaluate the Thermafil endodontic obturation
      technique and to compare it with laterally condensed gutta-percha. Thirty-seven
      maxillary central incisors were similarly prepared and divided into groups.
      Seventeen were obturated with Thermafil and 17 with lateral condensation. Three
      served as controls. After vacuum staining, all teeth were cleared and apical dye
      penetration was evaluated by two independent observers. Average leakage values
      were 0.24 mm and 1.32 mm for Thermafil and 0.47 mm and 1.18 mm for lateral
      condensation. There was no significant difference between the techniques,
      although a difference between evaluators was noted. Final results point to the
      relative subjectivity of in vitro leakage studies. When comparing the obturation
      times of both techniques, the Thermafil technique averaged 2 min 56 s while
      lateral condensation took 3 min 26 s. Statistical analysis showed no significant
      difference in obturation times.

PMID- 1402598
TI  - Anatomical study of the root apex in the maxillary anterior teeth.
AB  - The purpose of this study was to investigate anatomically the apical portion of
      the root canal of human maxillary anterior teeth. Thirty maxillary central
      incisors, 30 maxillary lateral incisors, and 30 maxillary cuspids were used.
      These were teeth from patients ranging in age from 11 to 73 yr. The root apex and
      main apical foramen coincided in 16.7% of central incisors and cuspids and in
      6.7% of the lateral incisors. The labiolingual diameter of the root canal at the
      apical constriction of the central incisors, lateral incisors, and cuspids
      averaged 0.425 mm, 0.369 mm, and 0.375 mm, respectively; and the respective
      vertical distances between apex and apical constriction were 0.863 mm, 0.825 mm,
      and 1.010 mm.

PMID- 1402599
TI  - The standardized stop: a new concept in endodontics.
AB  - This article presents a technique for making and using disposable standardized
      silicone stops. The stops have several diameters, colors, and thicknesses in
      order to make nonsurgical endodontics more efficient and improve the quality of
      therapy.

PMID- 1402600
TI  - Adverse response to vital bleaching.
AB  - A case study is presented that described an acute flare-up of a tooth following a
      vital bleaching procedure. The case illustrates (a) the importance of assessing
      the pulpal and periradicular status of a tooth prior to any vital bleaching
      procedure; and (b) the alteration of the local adaptation syndrome by the
      bleaching agent.

PMID- 1402601
TI  - Behavioral variability and frequency-dependent selection.
AB  - In Experiment 1, two conditions were compared: (a) a variability schedule in
      which food reinforcement was delivered for the fourth peck in a sequence that
      differed from the preceding N four-peck sequences, with the value of N
      continuously adjusted to maintain reinforcement probability approximately
      constant; and (b) a control condition in which the variability constraint was
      dropped but reinforcement probability remained constant. Pigeons responded
      approximately randomly under the variability schedule but showed strong
      stereotyped behavior under the control condition. Experiments 2 and 3 tested the
      idea that variability is the outcome of a type of frequency-dependent selection,
      namely differential reinforcement of infrequent behavior patterns. The results
      showed that pigeons alternate when frequency-dependent selection is applied to
      single pecks because alternation is an easy-to-learn stable pattern that
      satisfies the frequency-dependent condition. Nevertheless, 2 of 4 pigeons showed
      random behavior when frequency-dependent selection was applied to two pecks, even
      though double alternation is a permissible and stable stereotype under these
      conditions. It appears that random behavior results when pigeons are unable to
      acquire the stable stereotyped behavior under a given frequency-dependent
      schedule.

PMID- 1402602
TI  - Key pecking of pigeons under variable-interval schedules of briefly signaled
      delayed reinforcement: effects of variable-interval value.
AB  - Key pecking of 4 pigeons was maintained under a multiple variable-interval 20-s
      variable-interval 120-s schedule of food reinforcement. When rates of key pecking
      were stable, a 5-s unsignaled, nonresetting delay to reinforcement separated the
      first peck after an interval elapsed from reinforcement in both components. Rates
      of pecking decreased substantially in both components. When rates were stable,
      the situation was changed such that the peck that began the 5-s delay also
      changed the color of the keylight for 0.5 s (i.e., the delay was briefly
      signaled). Rates increased to near-immediate reinforcement levels. In subsequent
      conditions, delays of 10 and 20 s, still briefly signaled, were tested. Although
      rates of key pecking during the component with the variable-interval 120-s
      schedule did not change appreciably across conditions, rates during the variable
      interval 20-s component decreased greatly in 1 pigeon at the 10-s delay and
      decreased in all pigeons at the 20-s delay. In a control condition, the variable
      interval 20-s schedule with 20-s delays was changed to a variable-interval 35-s
      schedule with 5-s delays, thus equating nominal rates of reinforcement. Rates of
      pecking increased to baseline levels. Rates of pecking, then, depended on the
      value of the briefly signaled delay relative to the programmed interfood times,
      rather than on the absolute delay value. These results are discussed in terms of
      similar findings in the literature on conditioned reinforcement, delayed matching
      to sample, and classical conditioning.

PMID- 1402603
TI  - Competition between stimulus-reinforcer contingencies and anticipatory contrast.
AB  - Procedures used to study anticipatory contrast are conceptually similar to those
      used to study autoshaping, in that two target stimuli signal either higher or
      lower rates of reinforcement in the following components of the schedule. Despite
      this signal contingency, anticipatory contrast entails response rates that are
      higher to the target stimulus followed by the lower rate of reinforcement. To
      determine the relation between such effects and autoshaping, different variations
      of the procedure were used in which the signal contingency was presented in the
      absence of reinforcement in the target components themselves and in which the
      reinforcement schedules in the different following components were signaled by
      the same stimulus. Autoshaping effects of this signal contingency were
      demonstrated when no reinforcement was available during the target-component
      signals themselves. Intermediate patterns of behavior occurred when reinforcement
      was available during the target-component signals and when their different
      following schedules were correlated with the same stimulus. Attempts to isolate
      these signal and contrast effects functionally by using the signal-key procedure
      were unsuccessful. The results demonstrate that Pavlovian stimulus contingencies
      are in competition with the dynamics of anticipatory contrast, thus reducing its
      occurrence under some circumstances.

PMID- 1402604
TI  - Successive independence and behavioral contrast in a closed economy.
AB  - Two pigeons had access to multiple concurrent schedules of reinforcement for 24
      hours per day in their home cages. The variable-interval schedules comprising the
      multiple concurrent schedules were varied across 16 conditions. In three sets of
      conditions, one schedule was varied while its concurrent alternative and the
      concurrent schedules in the other component were held constant. Behavioral
      contrast was observed; that is, as the rate of reinforcement arranged by the
      varied schedule decreased, response rates on the constant schedules typically
      increased. These conditions formed part of two larger sets of conditions in which
      the concurrent schedules in one multiple-schedule component remained constant
      while the concurrent schedules in the other component were varied. Successive
      independence was found, in that behavior allocation during the constant component
      did not vary as a function of the reinforcer ratios in the varied component.
      Successive independence between components in multiple concurrent schedules is a
      robust result that occurs in closed economies and under conditions that promote
      behavioral contrast.

PMID- 1402605
TI  - Conjoint schedules of timeout deletion in pigeons.
AB  - This experiment attempted to bring behavior under joint control of two distinct
      contingencies, one that provided food and a second that extended the periods
      during which that food was available. Pigeons' responses on each of two keys were
      reinforced according to a single random-interval schedule of food presentation
      except during signaled timeout periods during which the schedule was temporarily
      disabled. By means of a conjoint schedule, responses on the initially less
      preferred key not only produced food but also canceled impending timeouts. When
      behavior came to predominate on this conjoint alternative, the consequences of
      responding on the two keys were reversed. Responding in 3 of 4 pigeons proved
      sensitive to the conjoint scheduled consequences, as evidenced by systematic
      shifts in response rates favoring the conjoint key. In 2 of these 3 pigeons,
      sensitivity to the conjoint contingency was evident under time-in:timeout ratios
      of 2:1 (time-in = 120 s, timeout = 60 s) and 1:5 (time-in = 30 s, timeout = 150
      s), whereas for the other pigeon preference for the conjoint key was observed
      only under the latter sequence of conditions. There was only weak evidence of
      control by the conjoint scheduled consequences in the 4th subject, despite
      extended training and forced exposure to the conjoint alternative. The overall
      pattern of results is consistent with studies of timeout avoidance but also
      shares features in common with positively reinforced behavior.

PMID- 1402606
TI  - Multisegmental analyses of acoustic startle in the flying cricket (Teleogryllus
      oceanicus): kinematics and electromyography.
AB  - Tethered, flying Australian field crickets (Teleogryllus oceanicus) stimulated
      with ultrasound respond with a rapid, short-latency turn from the sound source.
      We analyzed the kinematics of two behavioral components of this acoustic startle
      response and recorded electromyograms from the muscles involved in producing
      them. The two behavior patterns studied were the swing of the metathoracic leg,
      which has been shown to elicit a short-latency turn, and a lateral swing of the
      antennae, for which a direct role in steering has not been demonstrated. The
      kinematic data showed that when a pulse of ultrasound was presented to one side
      of the animal (1) the contralateral metathoracic leg abducted and elevated, while
      the ipsilateral leg remained in place, (2) both antennae swung laterally, but the
      contralateral antenna moved farther than the ipsilateral antenna, (3) increases
      in stimulus intensity elicited larger movements of the leg and contralateral
      antenna, while the ipsilateral antenna showed little sensitivity to stimulus
      intensity, and (4) for the leg, the latency to the onset of the swing decreased
      and the duration of the movement increased with increasing stimulus intensity.
      Electromyograms were recorded from the leg abductor M126 and two antennal
      muscles: the medial scapo-pedicellar muscle M6 and the lateral scapo-pedicellar
      muscle M7. M7 moves the antenna laterally, M6 moves it medially. Upon stimulation
      with ultrasound (1) both M126 and M7 showed increasing spike activity with
      increasing intensity of the ultrasound stimulus, (2) M126 showed a decrease in
      latency to the first spike and an increase in the duration of spike activity with
      increasing stimulus intensity, (3) latencies for M6 and M7 were not correlated
      with stimulus intensity, but M7 had significantly shorter latencies than M6 and
      the contralateral M7 had significantly shorter latencies than the ipsilateral M7,
      and (4) the ipsilateral M126 spiked in response to ultrasound in 6 of the 10
      animals tested. In these cases, however, latency to the first spike was
      substantially longer, and the spike frequency was lower than for the muscle's
      response to contralateral stimuli. We attempt to correlate these electromyogram
      data with the kinematic data and relate them to the relevance of the two behavior
      patterns to the execution of an escape response.

PMID- 1402607
TI  - Posterior lymph heart pressure and rate and lymph flow in the toad Bufo marinus
      in response to hydrated and dehydrated conditions.
AB  - Posterior lymph heart pressure, rate and flow were measured in chronically
      cannulated Bufo marinus during normal hydrated and dehydrated conditions. A new
      surgical technique was developed which allowed direct and constant measurement of
      the functioning of the posterior lymph hearts with minimal disruption to normal
      lymph drainage. The mean intra-lymph-heart systolic pressure was 2.29 +/- 0.12
      kPa for hydrated animals at rest, decreasing to 1.01 +/- 0.10 kPa after 24 h of
      dehydration. Similarly, lymph heart rate, which was 48.2 +/- 1.7 beats min-1
      under hydrated conditions, decreased to 31.8 +/- 4.6 beats min-1 after 18 h of
      dehydration. Lymph flow decreased almost to zero during dehydration from a
      hydrated rate of 1.11 +/- 0.04 ml h-1 100 g-1. This is the first study to measure
      directly and to correlate these variables in an amphibian and to show
      specifically that pressure, rate and lymph flow are significantly reduced during
      periods of dehydration.

PMID- 1402608
TI  - The stopping response of Xenopus laevis embryos: pharmacology and intracellular
      physiology of rhythmic spinal neurones and hindbrain neurones.
AB  - 1. Xenopus laevis embryos stop swimming in response to pressure on the cement
      gland. This behaviour and 'fictive' stopping are blocked by bicuculline (10 mumol
      1(-1)), tubocurarine (110 mumol 1(-1)) and kynurenic acid (0.5 mmol 1(-1)). 2.
      Intracellular recordings from spinal neurones active during swimming have shown
      that pressure on the cement gland evokes compound, chloride-dependent inhibitory
      postsynaptic potentials (IPSPs). These are blocked by bicuculline, tubocurarine
      and kynurenic acid, but are unaffected by strychnine (2 mumol 1(-1)). 3. When the
      cement gland is pressed, trigeminal ganglion activity precedes both the IPSPs and
      the termination of 'fictive' swimming activity recorded in rhythmic spinal
      neurones. The trigeminal discharge is unaffected by the antagonists bicuculline,
      tubocurarine, kynurenic acid and strychnine. 4. Intracellular recordings from the
      hindbrain have revealed neurones that are normally silent, but rhythmically
      inhibited during 'fictive' swimming. In these neurones pressure on the cement
      gland evokes depolarising potentials, often with one or more spikes. 5. We
      propose that the stopping response depends on the excitation of pressure
      sensitive trigeminal receptors which innervate the cement gland. These release an
      excitatory amino acid to excite brainstem GABAergic reticulospinal neurones,
      which inhibit spinal neurones to turn off the central pattern generator for
      swimming. There may also be a less direct pathway.

PMID- 1402609
TI  - Strenuous exercise-induced remodelling of mature bone: relationships between in
      vivo strains and bone mechanics.
AB  - Mature bone can adapt to strenuous exercise, but no study has correlated the
      changes in bone in vivo strains, remodelling and mechanical properties that occur
      as a consequence of strenuous training. Therefore, we examined exercise-related
      remodelling and in vivo strains in the tarsometatarsus (TMT) of three groups of
      adult (post-physial closure) White Leghorn roosters: basal control (30 weeks of
      age), age-matched control (39 weeks) and exercise (39 weeks). Exercise birds ran
      for 1 h a day, 5 days a week for 9 weeks at 70-75% of predicted maximum aerobic
      capacity. During treadmill locomotion, in vivo strains were recorded from
      miniature rosette strain gauges implanted on anterior, medial and lateral TMT
      cortices. TMT mechanical properties were measured with three-point bending tests
      to failure. Cortical morphometry was digitized from photographic slides of a 1-mm
      thick mid-diaphysial cross section of each bone. Exercise and age-matched control
      TMTs had significantly greater cortical area and maximum load than had basal
      controls. Exercise axial strains significantly exceeded basal and age-matched
      control strains along the anterior and lateral surfaces. Age-matched control
      anterior axial strain was twice that of the basal control. The mature bone
      remodelling suggested that the structural properties optimized by exercise
      induced remodelling may differ from those optimized by age-related remodelling.
      The findings support the osteoregulatory role of strain but contradict earlier
      data suggesting that strain magnitudes do not change significantly with age or
      exercise.

PMID- 1402610
TI  - Mechanical work rate minimization and freely chosen stride frequency of human
      walking: a mathematical model.
AB  - The interplay between the work done to move the body centre of mass with respect
      to the environment (external work) and the work done to move the limbs with
      respect to the body (internal work) has been shown experimentally partially to
      determine the freely chosen stride frequency during walking. A mathematical model
      that estimates the two components of the mechanical work is proposed. The model,
      according to the criterion of work rate minimization (both positive and positive
      plus negative), is able to predict the natural stride frequency as a function of
      the average progression speed. The adequacy of the model and the validity of the
      assumptions have been checked against measurements of natural stride frequency in
      11 subjects walking on a treadmill at several speeds (range 1-3 m s-1).
      Comparison with theoretical predictions shows good agreement with the
      minimization of positive work rate at low speeds, while at high speeds the stride
      frequency is better explained by the model for minimum positive plus negative
      work rate.

PMID- 1402611
TI  - Acid-base regulation in response to hypercapnia in the lymphatic and circulatory
      systems of the toad Bufo marinus.

PMID- 1402612
TI  - Relationship between heart rate and oxygen consumption during steady-state
      swimming in California sea lions.
AB  - Heart rate (fH) and rate of oxygen uptake (VO2) were measured in six subadult
      California sea lions Zalophus californianus while they were at rest and while
      they were swimming for 15 min at controlled speeds of up to 1.4 m s-1 and pulling
      loads of up to 3 kg. There was a good linear relationship between fH and VO2 in
      all six sea lions. The slopes of the individual regression lines varied between
      2.66 and 4.36 beats ml-1 O2 kg-1, the intercepts varied between 48.2 and 63.0
      beats min-1 and r2 varied between 0.82 and 0.93. The mean relationship for all
      six sea lions is fH = (57.4 +/- 2.0) + (3.58 +/- 0.23) VO2, r2 = 0.89 +/- 0.01.
      The mean of the lowest VO2 values was 5.1 +/- 0.4 ml min-1 kg-1 and the mean of
      the highest VO2 values was 26.9 +/- 1.9 ml min-1 kg-1. The means of the lowest
      and highest values of fH were less extreme, being 72 +/- 3 beats min-1 and 155 +/
      5 beats min-1, respectively. It is concluded that, by using data storage devices
      and grouped data, fH could be used in otariids as an indicator of aerobic
      metabolism under field conditions, in particular for breeding females during the
      period of lactation.

PMID- 1402614
TI  - Medical journals in transition--from author to reader.

PMID- 1402613
TI  - Development of segment- and target-related neuronal identity in the medicinal
      leech.
AB  - The rhythmic pumping of the paired heart tubes in the medicinal leech Hirudo
      medicinalis offers an excellent system for studying the development of a simple
      behavior in terms of its neuronal and muscular components. The present
      experiments examined the development of identified heart excitor (HE) motor
      neurons during normal embryogenesis. Using intracellular impalements and dye
      filling, we found that the HE motor neurons could be identified at an early stage
      of development and that they initially elaborated axonal arborizations in
      inappropriate target fields in the ventral body wall. These inappropriate
      projections were retracted as those at the appropriate target (developing heart
      tube muscle) extended. This remodelling occurred at least 4 days before the HEs
      acquired the adult phenotype of being driven to fire action potentials in a
      rhythmic pattern. Although the HEs exhibited centrally driven rhythmic
      oscillations late in embryogenesis, at earlier stages they exhibited largely a
      tonic discharge interrupted by bursts of inhibitory potentials in a periodic, but
      not a rhythmic, pattern. We also found what appeared to be non-rhythmic HE
      homologs in anterior and posterior segments where HE neurons have not been
      previously described. These homologs may project along similarly patterned
      guidance cues early in development, since they are at first indistinguishable
      from the definitive HEs, but they continued to elaborate both lateral and medial
      body wall projections over the same period that definitive HEs were expanding
      their arborizations over the developing heart tube and retracting their body wall
      projections. In both adult and embryonic leeches the homologs exhibited mostly
      tonic activity that was interrupted by pronounced, but non-rhythmic,
      hyperpolarizing postsynaptic potentials. Thus, there appears to be early
      segmental specification directing the final phenotype of the iterated neuron
      that, in most segments, becomes the HE motor neuron.

PMID- 1402615
TI  - Journalology: evolution of medical journals and some current problems.

PMID- 1402616
TI  - New paradigms in journalology.

PMID- 1402617
TI  - Medical journals and society: threats and responsibilities.

PMID- 1402618
TI  - Responsibilities of medical journals to readers.

PMID- 1402619
TI  - Thyrotropin-releasing hormone increases serum levels of growth hormone-releasing
      hormone and growth hormone in patients with acromegaly.
AB  - The effect of intravenous injection of thyrotropin-releasing hormone (TRH) on the
      plasma concentrations of growth hormone (GH) and growth hormone-releasing hormone
      (GHRH) was studied in seven patients with acromegaly and in five control
      subjects. TRH had no effect on plasma GH or GHRH in the five control subjects. A
      'paradoxical' increase in plasma GH in response to TRH was observed in four of
      the seven patients with acromegaly. In these four patients plasma GHRH also
      increased in response to TRH. No TRH-induced increase in GHRH levels was observed
      in the other three patients with acromegaly who did not display an increase in GH
      in response to TRH. The present results imply that GHRH may be involved in the
      plasma GH response to TRH in patients with acromegaly.

PMID- 1402620
TI  - Prednisolone in the treatment of severe malignant hypercalcaemia in metastatic
      breast cancer: a randomized study.
AB  - To determine the effect of prednisolone on severe hypercalcaemia in women with
      metastatic breast cancer, 30 patients with serum ionized calcium above 1.60 mmol
      l-1 (reference range 1.15-1.35 mmol l-1) entered a randomized trial. Performance
      status before entry to the trial and survival time after hypercalcaemia were also
      noted. All patients received 4 l of isotonic saline daily and 80 mg intravenous
      furosemide three times daily for 2 d; thereafter they received 3 l of isotonic
      saline daily and 80 mg furosemide twice daily for 6 d. Fifteen patients were
      randomized to receive prednisolone, 25 mg orally, three times daily for 8 d.
      Serum ionized calcium decreased significantly in both groups, but most markedly
      in the prednisolone group. The median difference was 0.28 mmol l-1 (95%
      confidence interval (CI), 0.09-0.52) on day 4 and 0.21 mmol l-1 (95% CI, 0.12
      0.44) on day 8. In seven prednisolone-treated patients serum ionized calcium
      normalized, compared to none in the control group (Fisher's exact test; P =
      0.028). No severe adverse effects were observed. Prior to detection of
      hypercalcaemia all patients were severely immobilized, primarily due to bone
      pain. Only 10 patients were still living after 3 months. Prednisolone, furosemide
      and rehydration is superior to furosemide and rehydration alone in severely
      hypercalcaemic patients with metastatic breast cancer in whom immobilization
      appears to be an early warning sign of life-threatening hypercalcaemia. The short
      survival time was not influenced by prednisolone.

PMID- 1402621
TI  - Decreased erythrocyte cholesterol/phospholipid ratio in untreated patients with
      essential hypertension.
AB  - The erythrocyte cholesterol/phospholipid ratio was determined in eight patients
      with untreated essential hypertension and compared with that of eight age-matched
      control subjects. The ratio was significantly lower in patients (Wilcoxon's
      paired rank test; P less than 0.01), and a correlation existed between the ratio
      and serum cholesterol concentration in patients (r = 0.63) but not in controls (r
      = 0.02). A reduction in the cholesterol/phospholipid ratio may play a direct role
      in destabilizing the plasma membrane, which will in turn result in an increase in
      membrane permeability in essential hypertension.

PMID- 1402622
TI  - Metabolic control and progression of complications in insulin-dependent diabetic
      patients after kidney transplantation.
AB  - Patient survival and progression of complications were monitored for 3 years
      after kidney transplantation in 29 type-1 diabetic patients. Ten age-matched, non
      diabetic kidney-transplanted patients served as controls. Five diabetic patients
      died during follow-up (three cardiovascular events, two infections), three
      diabetic patients had a non-fatal myocardial infarction and four developed
      cerebrovascular complications after transplantation. Of the diabetic patients,
      69% suffered from proliferative retinopathy before transplantation; 20% of them
      improved, 65% remained unchanged and 15% deteriorated after transplantation.
      Motor but not sensory conduction velocity measured from the nervus medianus
      improved after transplantation. Autonomic neuropathy was observed in 50% of the
      patients and was unaffected by transplantation. Glycaemic control did not improve
      significantly during follow-up (HbA1, 10.6 +/- 0.5% before and 9.5 +/- 0.6% 3
      years after transplantation). Body weight increased in both diabetic and non
      diabetic patients within 3 years after transplantation (from 68 +/- 2 to 77 +/- 6
      kg in diabetics, P less than 0.01; from 167 +/- 4 to 77 +/- 6 kg in non
      diabetics, P less than 0.01). Subcutaneous fat thickness measured from computer
      tomography scans of the calf increased in diabetic patients from 5.0 +/- 0.6 to
      6.1 +/- 0.9 mm (P less than 0.05). However, the cross-sectional areas of triceps
      and calf muscles did not increase, suggesting that the increase in body weight
      was solely due to an increase in fat. It is clear that diabetes-related
      complications continue to progress and are not influenced by a successful kidney
      transplant.

PMID- 1402623
TI  - Proinflammatory cytokines in cardiac myxomas.
AB  - Serum levels of various cytokines were measured in three patients with cardiac
      myxomas presenting with and without constitutional symptoms, immunological
      features and elevated plasma levels of interleukin-6. Interleukin-6 but not other
      cytokines (interleukin-1, tumour necrosis factor-alpha, interferon-gamma) relate
      to immunological features of the patients. Circulating levels of atrial
      natriuretic peptide correspond to haemodynamic changes but not to the tumour
      bearing state itself.

PMID- 1402624
TI  - Demonstration of a relationship between white blood cell count, insulin
      resistance, and several risk factors for coronary heart disease in women.
AB  - In order to evaluate the relationship between peripheral white blood cell (WBC)
      count, insulin-mediated glucose uptake, and several risk factors for coronary
      heart disease (CHD), WBC, plasma glucose and insulin responses to a 75-g oral
      glucose challenge, fasting plasma cholesterol, high-density-lipoprotein (HDL)
      cholesterol, and triglyceride concentration, and systolic and diastolic blood
      pressure were determined in 63 consecutive female volunteers with normal glucose
      tolerance. The results demonstrated the presence of statistically significant
      correlation coefficients between WBC count and both insulin-mediated glucose
      disposal (r = 0.50, P less than 0.001) and insulin response to oral glucose (r =
      0.50, P less than 0.001). Furthermore, WBC count correlated with plasma glucose
      response to oral glucose (r = 0.48, P less than 0.001), fasting plasma
      triglyceride (r = 0.37, P less than 0.005) and HDL-cholesterol concentrations (r
      = -0.38, P less than 0.005), and systolic (r = 0.22, P less than 0.1) and
      diastolic (r = 0.27, P less than 0.05) blood pressure. However, the only two
      variables significantly correlated with WBC count in multivariate regression
      analysis were insulin resistance (r = 0.49, P less than 0.01) and insulin
      response (r = 0.35, P less than 0.05). These data indicate that WBC count is
      significantly correlated with changes in carbohydrate and lipoprotein metabolism
      and blood pressure that increase the risk of CHD. However, it appears that these
      relationships are secondary to resistance to insulin-mediated glucose uptake and
      hyperinsulinaemia.

PMID- 1402625
TI  - Anaemia, iron-related measurements and erythropoietin levels in untreated
      patients with active leprosy.
AB  - The mechanisms responsible for anaemia in leprosy were studied prior to the
      institution of therapy in 56 patients with active disease. Haematological
      indices, iron-related measurements, inflammatory markers and erythropoietin
      levels were assessed, with bone-marrow studies being performed on anaemic
      patients. Anaemia was more common in the patients with lepromatous leprosy
      (85.7%) than it was in the rest of the group (19%). The lepromatous group
      exhibited the disordered iron transport of the anaemia of chronic disorders in
      that they had a significantly lower mean serum iron level (P less than 0.05), and
      a mildly raised serum ferritin concentration. Anaemic lepromatous patients also
      showed a blunted erythropoietin response compared with controls with non
      inflammatory anaemia. A subgroup of five anaemic subjects displayed apparently
      adequate transport of iron to the erythroid marrow (normal percentage transferrin
      saturations and appropriate sideroblast counts) and the blunted erythropoietin
      response appeared to be the dominant factor in the pathogenesis of their anaemia.
      Analysis of inflammatory markers revealed that while the erythrocyte
      sedimentation rate was very high in the lepromatous subjects, there was no
      concomitant rise in C-reactive protein concentration. This suggests the presence
      of a disordered cytokine-mediated acute phase response in the condition.

PMID- 1402626
TI  - Pulse cyclophosphamide therapy in Wegener's granulomatosis: a pilot study.
AB  - Five patients with Wegener's granulomatosis (WG) have been treated with 6- to 8
      monthly pulses of intravenous cyclophosphamide (CP) and glucocorticoids in an
      open pilot study. One patient achieved complete remission sustained during 30
      months of follow-up; one patient had features of active disease after 28 months
      of remission; two patients after an initial remission had an exacerbation of the
      disease and received continuous oral administration of CP, and one patient
      required continuous oral CP to control the symptoms. These results suggest that
      this regimen may not achieve a high degree of sustained remission in patients
      with WG.

PMID- 1402627
TI  - Association of type III cryoglobulinaemia and hepatitis C virus-related
      cirrhosis.

PMID- 1402628
TI  - Heart rate of physicians participating in the young investigators' award
      competition.

PMID- 1402629
TI  - Coronary artery disease in Chinese males without hypercholesterolaemia.

PMID- 1402630
TI  - Insulin sensitivity in alcoholics.

PMID- 1402631
TI  - Health promoting life styles--indeterminism versus determinism.

PMID- 1402632
TI  - Standardized use of simple criteria from case history improves selection of
      patients for cardiac-care unit (CCU) admission.
AB  - A simple algorithm, which improves the diagnostic performance in patients
      arriving with acute chest pain in the emergency room, has been developed. The
      algorithm is solely based on information immediately available to the physician
      and includes elements from ECG, clinical findings and case history. As
      postulated, a stepwise use of all these variables improved the diagnostic
      accuracy and reduced the false positive cardiac-care unit (CCU) referral rate in
      a prospective study of 1450 patients admitted with acute chest pain. Compared to
      previous hospital practice during a preceding control period, sensitivity in
      diagnosing patients with unstable ischaemic heart diseases increased from 86% to
      94% (P < 0.01), and specificity increased from 44% to 56% (P < 0.001).
      Accordingly, accuracy increased from 67% to 81% (P < 0.001), and false positive
      CCU-admission rate decreased from 35% to 19%. The greatest improvement in
      physician's diagnostic decisions was observed among patients without clear-cut
      signs of acute ischaemic heart disease on admission.

PMID- 1402633
TI  - Dietary intake of 70- to 89-year-old men in eastern and western Finland.
AB  - A detailed dietary history interview of 70- to 89-year-old men, 98 from eastern
      and 129 from western Finland, was obtained as part of a 30-year follow-up survey
      within the Seven Countries Study. The average energy intake was similar in level,
      about 2700 kcal, in both areas. The percentage of total energy intake from fat
      was 39.1% in the west, and 36.5% in the east. The P/S ratio was about the same,
      0.27 and 0.29, in eastern and western areas, respectively. The intake of most
      micronutrients was similar in the two cohorts. Only the intake of vitamins A and
      C and phosphorus, manganese, copper and zinc was higher in eastern Finland than
      in western Finland. The nutritional density of the diet of the eastern cohort was
      slightly higher than that of the western one due to their higher consumption of
      rye products, vegetables and berries, and also sour milk and fish and fish
      products. The diet met the general recommendations and was comparable to that of
      younger age groups.

PMID- 1402634
TI  - Metabolism of plasma low density lipoproteins in familial combined
      hyperlipidaemia: effect of acipimox therapy.
AB  - Ten male patients with familial combined hyperlipidaemia (FCHL) were studied with
      regard to LDL metabolism and composition. The FCHL patients had higher LDL levels
      than healthy controls (5.4 +/- 1.4 vs. 3.7 +/- 0.7 mmol l-1; P < 0.005) and a
      higher rate of production of the lipoprotein (15.8 +/- 3.1 mg kg-1 d-1 in FCHL
      vs. 13.1 +/- 1.8 mg kg-1 d-1 in the normals; P < 0.005). The fractional catabolic
      rate of LDL was low-normal in the FCHL patients, with a high level of
      interindividual variation. The actual individual LDL cholesterol level within the
      FCHL patient group appeared to be more closely associated with the LDL apoB FCR
      value than the rate of production of the particle. Analysis of the LDL particles
      from FCHL patients revealed a relative enrichment in triglycerides, while the
      cholesterol content of the lipoprotein was normal. Institution of acipimox
      therapy in 8 patients reversed the high rate of synthesis of LDL (15.2 +/- 3.5 mg
      kg-1 d-1) to a more normal level (13.9 +/- 4.0 mg kg-1 d-1; P = 0.08), while the
      FCR did not change significantly. In conclusion, patients with FCHL show an
      apparent overproduction of LDL apoB, while the actual degree of LDL elevation
      appears to be dependent on the clearance capacity of the lipoprotein, measured as
      LDL apoB FCR. The overproduction defect of LDL apoB can, at least in part, be
      managed by treatment with the nicotinic acid analogue acipimox.

PMID- 1402635
TI  - Ultrasound appearances in de Quervain's subacute thyroiditis with long-term
      follow-up.
AB  - In order to determine whether permanent echo abnormalities are produced by
      subacute thyroiditis, ultrasound examination of the thyroid was performed
      repeatedly after a mean interval of 23 months in 17 subjects (8 women and 9 men)
      aged 31-52 (mean 41) years, suffering from subacute thyroiditis. The diagnosis
      was based on typical clinical symptoms, and cytological confirmation was obtained
      in all subjects but one. In the primary phase the ultrasonic finding was in all
      cases abnormal, showing either diffuse or focal hypoechogenicity and enlargement
      of thyroid lobes. At follow-up, a homogenous echo structure was found in 15
      patients. Nodularity was detected in only two subjects. It is concluded that
      permanent focal echo abnormalities are generally not produced by subacute
      thyroiditis. Consequently, thyroid nodules in subjects with a history of SAT
      should not be ignored.

PMID- 1402636
TI  - Use of smokeless tobacco: blood pressure elevation and other health hazards found
      in a large-scale population survey.
AB  - Health hazards associated with the use of smokeless tobacco were evaluated in a
      cross-sectional study of 97,586 Swedish construction workers undergoing health
      examinations in 1971-74. All users of smokeless tobacco only (5014 subjects) and
      all exclusive smokers of > or = 15 cigarettes daily (8823 subjects) were compared
      with all non-users of any tobacco (23,885). Both smokeless tobacco users and
      smokers showed higher prevalences of circulatory and respiratory disorders.
      Hypertension was most common in smokeless tobacco users. In the 45- to 56-years
      age group, the odds ratio for a diastolic blood pressure of > 90 mmHg was 1.8
      (95% CI, 1.5-2.1), and for a systolic blood pressure > 160 mmHg, 1.7 (95% CI, 1.3
      2.1). Smokers showed the lowest prevalence of hypertension. Disability pensions
      due to cardiovascular disease were nearly 50% more frequent in both smokeless
      tobacco users and smokers. These findings indicate that an increased
      cardiovascular risk is also associated with the use of smokeless tobacco.

PMID- 1402637
TI  - Fasting insulin, calcium metabolism and the electrocardiogram in hypertensive
      subjects.
AB  - Changes in both calcium and insulin metabolism have been described in essential
      hypertension. Low levels of plasma ionized calcium (Ca2+) and high levels of
      insulin have previously been associated with vascular complications and coronary
      heart disease. In the present study, indices of calcium metabolism and fasting
      serum insulin were related to electrocardiographic (ECG) variables in 58 patients
      with untreated hypertension. Fasting insulin was found to be related to heart
      rate (r = 0.47, P < 0.001), diastolic interval (r = -0.39, P < 0.004) and
      electrical axis (r = -0.29, P < 0.03) while Ca2+ was found to be correlated with
      the QRS amplitude (r = -0.32, P < 0.03) and diastolic interval (r = 0.37, P <
      0.02). Furthermore, non-ionized serum calcium was correlated with the QRS
      duration (r = 0.36, P < 0.02), ST-segment interval (r = -0.49, P < 0.002) and QT
      interval (QoT, r = -0.42, P < 0.008). These correlations were still significant
      when the influences of age, sex, obesity, blood pressure and heart rate were
      taken into account in the multiple regression analysis. In conclusion, the
      present study demonstrates that calcium and insulin metabolism are related to
      several basic characteristic functions of the heart, such as the systolic and
      diastolic function, as well as to signs of left ventricular hypertrophy.

PMID- 1402638
TI  - Evaluation of regional body fat distribution: comparison between W/H ratio and
      computed tomography in obese women.
AB  - Measurements of regional body fat distribution as determined by waist-to-hip
      ratio and visceral-to-subcutaneous adipose tissue ratio were compared in 63 obese
      women. Subjects were divided into three CT-evaluated tertiles on the basis of
      visceral-to-subcutaneous adipose tissue ratio (group I, 0.05-0.231; group II,
      0.232-0.344; group III, 0.345-0.781). The three groups showed no appreciable
      differences in body weight, body mass index or total abdominal adipose tissue.
      Waist-to-hip ratio values were significantly lower in group I than in groups II
      and III. There was no statistically significant difference between groups II and
      III. Visceral abdominal adipose tissue was significantly and progressively higher
      in the three groups. Subcutaneous abdominal adipose tissue was significantly
      lower in group III than in group I. All metabolic variables and systolic and
      diastolic blood pressure were higher when visceral-to-subcutaneous adipose tissue
      ratio cut-off values were increased. Waist-to-hip ratio was significantly
      correlated with total adipose tissue, body mass index, visceral abdominal adipose
      tissue and subcutaneous abdominal adipose tissue. Visceral-to-subcutaneous
      adipose tissue ratio was correlated with visceral abdominal adipose tissue (r =
      0.84, P < 0.01) and subcutaneous abdominal adipose tissue (r = -0.28, P < 0.05).
      There was no correlation between visceral-to-subcutaneous adipose tissue ratio
      and body mass index or total abdominal adipose tissue. Visceral-to-subcutaneous
      adipose correlated more closely with metabolic variables than did waist-to-hip
      ratio. Partial correlations between waist-to-hip ratio and visceral-to
      subcutaneous adipose tissue ratio and metabolic variables, adjusted for body mass
      index, showed statistically significant relationships for visceral-to
      subcutaneous adipose tissue ratio, but not for waist-to-hip ratio. Visceral-to
      subcutaneous adipose tissue ratio correlated with waist-to-hip ratio in the study
      population as a whole, but only in group I did the correlation between visceral
      to-subcutaneous adipose tissue ratio and waist-to-hip ratio prove statistically
      significant. The present study demonstrates that visceral-to-subcutaneous adipose
      tissue ratio is a better index of body fat distribution than waist-to-hip ratio.

PMID- 1402639
TI  - Lipoprotein [Lp(a)] and peripheral vascular disease.
AB  - Lipoprotein(a) [Lp(a)], which combines structural elements of the lipid and
      fibrinolytic systems, is a major independent risk factor for the development of
      coronary heart disease. Eighty-four consecutive patients with peripheral vascular
      disease (of whom 42 had concomitant ischaemic heart disease) and 43 healthy
      controls were enrolled in a case-control study. We found that the mean Lp(a)
      concentration in male patients with peripheral vascular disease (PVD) was almost
      threefold higher than that of controls, while in female patients the Lp(a)
      concentration was more than twice that of controls. This marked difference was
      borne out in patients with and without concomitant ischaemic heart disease (IHD).
      A multivariate logistic regression analysis indicated that Lp(a) is independently
      associated with PVD when adjusted for age and sex (odds ratio per 100 mg l-1
      increase in Lp(a) = 1.35; P < 0.01). A similar association is observed for
      patients with concomitant IHD (odds ratio per 100 mg l-1 increase in Lp(a) =
      1.65; P < 0.01).

PMID- 1402640
TI  - Hypersensitivity reaction associated with acute hepatic dysfunction following a
      single intravenous dose of procainamide.
AB  - Rare cases of hepatotoxicity have been attributed to the antiarrhythmic agent
      procainamide. We here describe the case of a patient who had a hypersensitivity
      reaction to procainamide with fever, chills, arthralgia, abdominal pain and acute
      elevations of serum aminotransferase activities and bilirubin concentration. The
      reaction occurred after the patient had received a large intravenous dose during
      cardiac electrophysiological testing. This case should alert physicians to
      potential hepatotoxic reactions to procainamide, particularly with the increasing
      popularity of cardiac electrophysiological testing, during which this drug is
      commonly used.

PMID- 1402641
TI  - Autosomal dominant 'Mediterranean fever' in a Finnish family.
AB  - A 23-year-old Finnish man was examined because of an 8-year history of recurrent
      bouts of fever and abdominal pain. His father had been repeatedly investigated
      because of similar episodes since he was 24 years old, and one of the father's
      sisters was reported to have had recurrent periods of fever. The clinical
      features closely resembled those of familial Mediterranean fever (FMF), a
      syndrome rarely described in families of European descent. Unlike typical FMF,
      which is inherited as an autosomal recessive trait, the mode of inheritance of
      the syndrome in our family may be regarded as dominant. During a recent attack,
      serum concentrations of interleukin-1-beta, interleukin-6 and acute phase
      reactants, including serum amyloid A protein, were high. No signs of amyloidosis
      were detected in our patients.

PMID- 1402642
TI  - Plasma endotoxin in patients with quiescent Crohn's disease.

PMID- 1402643
TI  - Does graft-violates-host disease give a better indication of what goes on than
      graft-versus-host disease?

PMID- 1402644
TI  - Cryoglobulinaemia associated with hepatitis C virus infection: a report of 13
      cases.

PMID- 1402645
TI  - Treatment of giant cell arteritis with cyclophosphamide pulses.

PMID- 1402646
TI  - Transient renal dysfunction in diabetic patients after IVIg therapy.

PMID- 1402647
TI  - Identification of a motif for HLA-DR1 binding peptides using M13 display
      libraries.
AB  - Oligonucleotides encoding peptides known to bind to HLA-DR1 molecules have been
      inserted into the gene III of filamentous M13 phages. DR1 molecules purified from
      human lymphoblastoid cell lines could specifically bind to these peptide
      sequences expressed on the phage surface. A M13 phage peptide library was next
      constructed and screened with DR1 molecules. After four rounds of selection, more
      than 80% of the phages were able to bind to DR1. Competition experiments with
      both isolated phages and corresponding synthetic peptides showed that the binding
      was specific. Sequence analysis of the peptide encoding region of 60 phages
      binding to DR1 molecules and comparison with phages of the original library
      revealed two potential anchor positions. The first was an aromatic residue (Tyr,
      Phe, or Trp) at the NH2 terminus of the peptide sequences, and the second was
      located three residues downstream and consisted of Met or Leu. In addition, the
      negatively charged amino acids Asp and Glu were mostly excluded from the DR1
      binding sequences, and the small amino acid residues Gly and Ala were enriched at
      position 6. As for DR1, this approach should enable one to easily determine the
      binding motifs of other MHC class II alleles and isotypes. Furthermore, it could
      have interesting applications in the design of major histocompatibility complex
      specific antagonists.

PMID- 1402648
TI  - Differential structure-function requirements of the transmembranal domain of the
      B cell antigen receptor.
AB  - By generating phosphorylcholine (PC)-specific, wild-type (mu), and chimeric (mu-I
      A alpha) antigen receptor transfectants of mature B cells, we have shown that the
      COOH terminus of the mu heavy chain is essential for three major functions:
      immediate signal transduction (measured as changes in intracellular Ca2+),
      antigen presentation, and induction of immunoglobulin M secretion. A more
      detailed analysis of structural requirements of the COOH-terminal domains
      contributing to these functions was achieved by systematically replacing the
      spacer, cytoplasmic, and transmembranal domains of the mu-I-A alpha chimeric
      chain with those of mu. Using this rescue approach, we show that the carboxyl two
      thirds of the transmembranal domain (proximal to the cytoplasmic domain) is
      required for induction of intracellular Ca2+, whereas the complete transmembranal
      domain is required for the function of antigen presentation but is dispensable
      for induction of antibody secretion.

PMID- 1402649
TI  - Impairment of macrophage functions after ingestion of Plasmodium falciparum
      infected erythrocytes or isolated malarial pigment.
AB  - Human monocyte-derived macrophages ingest diamide-treated red blood cells (RBC),
      anti-D immunoglobulin (Ig)G-opsonized RBC, or Plasmodium falciparum ring-stage
      parasitized RBC (RPRBC), degrade ingested hemoglobin rapidly, and can repeat the
      phagocytic cycle. Monocytes fed with trophozoite-parasitized RBC (TPRBC), which
      contain malarial pigment, or fed with isolated pigment are virtually unable to
      degrade the ingested material and to repeat the phagocytic cycle. Monocytes fed
      with pigment display a long-lasting oxidative burst that does not occur when they
      phagocytose diamide-treated RBC or RPRBC. The phorbol myristate acetate-elicited
      oxidative burst is irreversibly suppressed in monocytes fed with TPRBC or
      pigment, but not in monocytes fed with diamide-treated or IgG-opsonized RBC. This
      pattern of inhibition of phagocytosis and oxidative burst suggests that malarial
      pigment is responsible for the toxic effects. Pigment iron released in the
      monocyte phagolysosome may be the responsible element. 3% of total pigment iron
      is labile and easily detached under conditions simulating the internal
      environment of the phagolysosome, i.e., pH 5.5 and 10 microM H2O2. Iron liberated
      from pigment could account for the lipid peroxidation and increased production of
      malondialdehyde observed in monocytes fed with pigment or in RBC ghosts and
      liposomes incubated at pH 6.5 in presence of pigment and low amounts of H2O2.
      Removal of the labile iron fraction from pigment by repeated treatments with 0.1
      mM H2O2 at pH 5.5 reduces pigment toxicity. It is suggested that iron released
      from ingested pigment is responsible for the intoxication of monocytes. In acute
      and chronic falciparum infections, circulating and tissue-resident phagocytes are
      seen filled with TPRBC and pigment particles over long periods of time. Moreover,
      human monocytes previously fed with TPRBC are unable to neutralize pathogenic
      bacteria, fungi, and tumor cells, and macrophage responses decline during the
      course of human and animal malaria. The present results may offer a mechanistic
      explanation for depression of cellular immunity in malaria.

PMID- 1402650
TI  - Interleukin 3 protects murine bone marrow cells from apoptosis induced by DNA
      damaging agents.
AB  - Murine bone marrow-derived cells, dependent on interleukin 3 (IL-3) for their
      growth in culture, undergo programmed cell, or apoptosis, upon cytokine
      withdrawal. Here it is reported that a variety of DNA damaging agents cause a
      more rapid onset of apoptosis in a factor-dependent cell line, BAF3, deprived of
      IL-3. In contrast, when cultured in the presence of IL-3, or other growth
      promoting factors, BAF3 cells are highly resistant to X-irradiation and the
      cytotoxic drugs etoposide and cisplatin. Overexpression of the bcl2 gene product
      also protects BAF3 cells from DNA damage. The presence of IL-3 is not required
      during the initial events of DNA damage or its repair. In the absence of IL-3,
      cells still complete the repair of DNA breaks within 15 min, and continue to
      cycle for 5 h. At this time, IL-3 is necessary to prevent the accelerated onset
      of DNA cleavage from a G2 arrest point.

PMID- 1402651
TI  - Myristyl acylation of the tumor necrosis factor alpha precursor on specific
      lysine residues.
AB  - NH2-terminal glycine myristyl acylation is a cotranslational modification that
      affects both protein localization and function. However, several proteins that
      lack NH2-terminal glycine residues, including the interleukin 1 (IL-1)
      precursors, also contain covalently linked myristate. To date, the site(s) of
      acylation of these proteins has not been determined. During an evaluation of IL-1
      acylation, it was observed that [3H]myristate-labeled human monocyte lysates
      contained a prominent 26-kD myristylated protein, which was identified as the
      tumor necrosis factor alpha (TNF) precursor protein on the basis of specific
      immune precipitation. Radioimmunoprecipitates from the supernates of labeled
      monocytes indicated that the processed or mature 17-kD form of TNF does not
      contain myristate, suggesting that the site of acylation occurs within the 76
      amino acid propiece of the precursor molecule. As the TNF precursor does not
      contain an NH2-terminal glycine, we hypothesized that myristyl acylation occurs
      on the N-epsilon-NH2 groups of lysine, of which two are present in the propiece
      (K19K20). Synthetic peptides were designed to include all seven lysine residues
      present within the entire 26-kD TNF precursor, and used in an in vitro myristyl
      acylation assay containing peptide, myristyl-CoA, and monocyte lysate as a source
      of enzyme. Analysis of reaction products by reverse phase high performance liquid
      chromatography and gas phase sequencing demonstrated the exclusive myristyl
      acylation of K19 and K20, consistent with the presence in monocytes of a specific
      lysyl N-epsilon-NH2-myristyl transferase activity. The acylated lysine residues
      are located immediately downstream from a hydrophobic, probable membrane-spanning
      segment of the propiece. Specific myristyl acylation of the TNF propiece may
      facilitate membrane insertion or anchoring of this critical inflammatory
      mediator.

PMID- 1402652
TI  - Defective maintenance of T cell tolerance to a superantigen in MRL-lpr/lpr mice.
AB  - In normal mice neonatal injection of staphylococcal enterotoxin B (SEB) induces
      tolerance in T cells that express reactive T cell receptor (TCR) V beta regions.
      To determine if a T cell neonatal defect was present in MRL-lpr/lpr mice, 20
      micrograms of SEB was injected intraperitoneally every other day into V beta 8.2
      TCR transgenic and nontransgenic MRL(-)+/+ and MRL-lpr/lpr mice from birth to 2
      wk of age. At 2 wk of age, V beta 8+ T cells were depleted, and SEB reactivity
      was lost, in spleen, lymph node, and thymus. These effects were equivalent in +/+
      and lpr/lpr SEB-tolerized mice. However, MRL-lpr/lpr mice failed to maintain
      neonatal tolerance. By 4 wk of age, there was a dramatic increase in T cells
      expressing V beta 8.2 in the peripheral lymph nodes of MRL-lpr/lpr mice but not
      MRL(-)+/+ mice. In vitro stimulation with SEB or TCR crosslinking revealed a
      total loss of neonatal tolerance 2 wk after cessation of SEB treatment in lpr/lpr
      mice, but not +/+ mice. The time-course of recovery of V beta 8+ T cells and
      reactivity to SEB and TCR crosslinking in the thymus of MRL-lpr/lpr mice was
      similar to that in the lymph node. Thymectomy at 2 wk of age eliminated tolerance
      loss in lymph nodes of MRL-lpr/lpr mice at 4 wk of age, indicating that loss of
      peripheral tolerance was due to the emigration of untolerized T cells from the
      thymus. Challenge of neonatally tolerized MRL-lpr/lpr mice with SEB (100
      micrograms, i.p.) at 8 wk of age resulted in a dramatic onset of T cell-mediated
      autoimmune disease characterized by 30% weight loss and 60% morality. This
      indicated that loss of tolerance to SEB also occurred in vivo. In contrast,
      neonatally tolerized MRL(-)+/+ mice remained totally unresponsive to SEB
      challenge and did not undergo any detectable weight loss. These results suggest
      that there is normal induction of neonatal tolerance to SEB in lpr/lpr mice, but
      that tolerance is not maintained after the tolerizing antigen is removed. This
      loss of neonatal tolerance can lead to severe weight loss and death on exposure
      to the tolerizing antigen later in life.

PMID- 1402653
TI  - Extensive and selective mutation of a rearranged VH5 gene in human B cell chronic
      lymphocytic leukemia.
AB  - B cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent
      of a human CD5+ B cell. Previous studies have shown that the VH and VL genes
      rearranged and/or expressed in CLL have few and apparently random mutations.
      However, in this study, we have found that the rearranged VH251 gene, one of the
      three-membered VH5 family, has extensive and selective mutations in B-CLL cells.
      Somatic mutation at the nucleotide level is 6.03% in B-CLLs whereas the somatic
      mutation levels are much lower in CD5+ and CD5- cord B cells, adult peripheral
      blood B cells, and Epstein-Barr virus-transformed CD5+ B cell lines (0.45, 0.93,
      and 1.92%, respectively). Complementary determining region 1 (CDR1) mutation in
      CLLs is particularly prevalent, and interchanges in CDRs often lead to
      acquisition of charge. Analysis of somatic mutations and mutations to charged
      residues demonstrated that the mutations in CLLs are highly selected.

PMID- 1402654
TI  - Impaired intracellular transport and cell surface expression of nonpolymorphic
      HLA-E: evidence for inefficient peptide binding.
AB  - The assembly of the classical, polymorphic major histocompatibility complex class
      I molecules in the endoplasmic reticulum requires the presence of peptide ligands
      and beta 2-microglobulin (beta 2m). Formation of this trimolecular complex is a
      prerequisite for efficient transport to the cell surface, where presented
      peptides are scanned by T lymphocytes. The function of the other class I
      molecules is in dispute. The human, nonclassical class I gene, HLA-E, was found
      to be ubiquitously transcribed, whereas cell surface expression was difficult to
      detect upon transfection. Pulse chase experiments revealed that the HLA-E heavy
      chain in transfectants, obtained with the murine myeloma cell line P3X63-Ag8.653
      (X63), displays a significant reduction in oligosaccharide maturation and
      intracellular transport compared with HLA-B27 in corresponding transfectants. The
      accordingly low HLA-E cell surface expression could be significantly enhanced by
      either reducing the culture temperature or by supplementing the medium with human
      beta 2m, suggesting inefficient binding of endogenous peptides to HLA-E. To
      analyze whether HLA-E binds peptides and to identify the corresponding ligands,
      fractions of acid-extracted material from HLA-E/X63 transfectants were separated
      by reverse phase HPLC and were tested for their ability to enhance HLA-E cell
      surface expression. Two fractions specifically increased the HLA class I
      expression on the HLA-E transfectant clone.

PMID- 1402655
TI  - Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for
      activation-induced apoptosis.
AB  - During human immunodeficiency virus (HIV) infection there is a profound and
      selective decrease in the CD4+ population of T lymphocytes. The mechanism of this
      depletion is not understood, as only a small fraction of all CD4+ cells appear to
      be productively infected with HIV-1 in seropositive individuals. In the present
      study, crosslinking of bound gp120 on human CD4+ T cells followed by signaling
      through the T cell receptor for antigen was found to result in activation
      dependent cell death by a form of cell suicide termed apoptosis, or programmed
      cell death. The data indicate that even picomolar concentrations of gp120 prime T
      cells for activation-induced cell death, suggesting a mechanism for CD4+ T cell
      depletion in acquired immune deficiency syndrome (AIDS), particularly in the face
      of concurrent infection and antigenic challenge with other organisms. These
      results also provide an explanation for the enhancement of infection by certain
      antibodies against HIV, and for the paradox that HIV appears to cause AIDS after
      the onset of antiviral immunity.

PMID- 1402656
TI  - Induction of tolerance to autoimmune diabetes with islet antigens.
AB  - The development of T cell tolerance to self-antigens is imparted principally
      through negative selection events during thymic ontogeny. However, this tolerance
      may be limited to antigens that are expressed in the thymus, and additional
      mechanisms are probably required to regulate autoimmune responses to tissue
      specific antigens. Autoimmune diabetes can be induced experimentally by treating
      susceptible stains of mice with multiple low doses of streptozotocin (STZ). In
      this report we show that transplantation of isolated islets of Langerhans into
      the thymuses of adult C57BL/KsJ mice will induce tolerance to the subsequent
      induction of autoimmune diabetes. This tolerance is tissue specific and thymus
      dependent. It was not induced by thymic transfer of adrenal tissue or by kidney
      transfer of islets. Furthermore, depletion of mature T cells was required and the
      tolerant state was abrogated by the adoptive transfer of normal splenocytes. It
      is interesting that pretreatment of the islets with STZ enhanced their ability to
      induce tolerance, and suggests that antigen shedding induced by tissue damage may
      facilitate transfer of islet antigens to tolerizing cells in the thymus. These
      findings indicate that thymic tolerance specific for tissue can be stimulated to
      occur in the presence of atopic tissue-specific intrathymic antigens. Elimination
      of disease-related T cells in the absence of global immunosuppression represents
      a novel approach for the prevention of autoimmune disease.

PMID- 1402657
TI  - Definition of interferon gamma-response elements in a novel human Fc gamma
      receptor gene (Fc gamma RIb) and characterization of the gene structure.
AB  - The human Fc gamma RI (CD64) is a high affinity receptor for the Fc portion of
      immunoglobulin (Ig), and its constitutively low expression on the cell surface of
      monocyte/macrophage and neutrophils is selectively upregulated by interferon
      gamma (IFN-gamma) treatment (Perussia, B., E. T. Dayton, R. Lazarus, V. Fanning,
      and G. Trinchieri. 1983. J. Exp. Med. 158:1092). Three distinct cDNAs have been
      cloned and code for proteins that predict three extracellular Ig-like domains
      (Allen, J.M., and B. Seed. 1989. Science [Wash. DC]. 243:378). Several
      differences in the coding region of these cDNAs suggest that in addition to
      polymorphic differences a second Fc gamma RI gene could possibly exist. This
      alternative Fc gamma RI gene (Fc gamma RIb) was defined by the lack of a genomic
      HindIII restriction site (van der Winkel, J. G. J., L. U. Ernst, C. L. Anderson,
      and I. M. Chiu. 1991. J. Biol. Chem. 266:13449). We describe the characterization
      a second gene (Fc gamma RIb) that has a termination codon in the third
      extracellular domain and therefore predicts a soluble form of a termination codon
      in the third extracellular domain and therefore predicts a soluble form of the
      receptor. We also define two distinct IFN-gamma-responsive regions in the 5'
      flanking sequence of Fc gamma RIb that resemble motifs that have been defined in
      the class II major histocompatibility complex promoter. The Fc gamma RIb promoter
      does not possess canonical TATA or CCAAT boxes, but does possess a palindromic
      motif that closely resembles the initiator sequence identified in the terminal
      deoxynucleotidyl transferase/human leukocyte IFN/adeno-associated virus type II
      P5 gene promoters (Smale, S. T., and D. Baltimore. 1989. Cell. 57:103; Seto, E.,
      Y. Shi, and T. Shenk. 1991. Nature [Lond.]. 354:241; Roy, A. L., M. Meisterernst,
      P. Pognonec, and R. C. Roeder. 1991. Nature [Lond.]. 354:245) virus type II P5
      gene promoters raising interesting questions as to its role in the basal and
      myeloid-specific transcription of this gene.

PMID- 1402658
TI  - Clonal expansion in follicular lymphoma occurs subsequent to antigenic selection.
AB  - The genesis of human follicular lymphoma (FL) is a multistep process. The initial
      event is thought to be the chromosomal translocation t(14;18)(q32;q21)
      juxtaposing the bcl-2 proto-oncogene with the immunoglobulin (Ig) H chain locus
      joining segment (JH) as an error of D-J or V-D joining in the pre-B cell.
      However, FL is recognized clinically as a tumor of surface Ig (sIg)-positive B
      cells with morphologic and phenotypic similarities to the centrocyte of the
      secondary immune response. Thus, additional steps must be involved in the clonal
      expansion of the FL tumor cell beyond the activation of bcl-2 as a consequence of
      the t(14;18) translocation. Like the normal centrocyte, somatic mutations
      accumulate in the variable (V) genes of FL tumor B cells. To determine if clonal
      expansion of FL occurs before or after the development of the malignant follicle,
      we sought to examine the evolution of the FL V gene from its unmutated germline
      (GL) counterpart. To obtain the GL gene we first cloned the productively
      rearranged V gene of patient MT FL and obtained the clone rMTF. A hybridization
      probe derived from the 2.1-kb region upstream of the V gene in clone rMTF
      identified a single band in Southern blot hybridization of GL DNA. This probe was
      used to screen a size-selected library, and candidate GL V genes were isolated.
      Two identical clones, MTGL1 and 2, proved to have upstream regions (USRs) that
      were colinear with the USR of the rMTF. Thus, the MTGL clones represent the
      unmutated GL V genes, which were productively rearranged in the MT FL. Comparison
      of the GL V gene sequence to a consensus of MT FL V gene sequences revealed 42
      mutations, demonstrating that malignant clonal expansion occurred subsequent to
      the activation of somatic mutation, presumably in the malignant follicle.
      Furthermore, the individual FL V gene sequences segregated into two distinct
      patterns of mutation. The major population represented 71% of the clones, and the
      minor population 29%. To investigate possible mechanisms for the parallel
      selection of distinct tumor cell populations, we analyzed the pattern of silent
      and replacement mutations within the V gene sequences. We found that in the
      framework regions (FRs) of both populations there were significantly fewer
      replacement changes than expected, suggesting that negative selective pressure
      was maintaining the structural integrity of the sIg. In contrast, the
      complementarity determining regions (CDRs), which make up the antigen binding
      domain of Ig, had an excess of replacement changes, suggesting positive selection
      for altered ligand binding.

PMID- 1402659
TI  - Transplantable myeloproliferative disease induced in mice by an interleukin 6
      retrovirus.
AB  - Lethally irradiated mice transplanted with bone marrow cells infected with a
      novel recombinant retrovirus (murine stem cell virus-interleukin 6 [MSCV-IL-6])
      bearing a mouse IL-6 gene developed a fatal myeloproliferative disease within 4
      wk of engraftment. The hematologic manifestations of the syndrome included
      elevated peripheral leukocyte counts (up to 430 x 10(3) cells/mm3) with a
      predominance of neutrophilic granulocytes, microcytic anemia, and thrombocytosis
      or thrombocytopenia. The mice showed extensive neutrophil infiltration of the
      lungs, liver, and occasionally lymph nodes, plus splenomegaly resulting from
      enhanced splenic myelopoiesis (30-60-fold increase in progenitor numbers).
      Despite the chronic stimulation of neutrophil excess by IL-6, bone marrow from
      affected mice was capable of repopulating the hematopoietic tissues (bone marrow
      and spleen) of lethally irradiated hosts during repeated serial transplantation.
      In the longest documented case, the progeny of a single MSCV-IL-6-marked cell
      transferred the myeloproliferative disease to two secondary, four tertiary, and
      two quaternary recipients (the clone endured for a total of 72 wk). These
      results, demonstrating considerable proliferative longevity of the IL-6-producing
      cells, support an in vivo role of IL-6 in the maintenance of hematopoietic
      precursors. Dysregulated IL-6 production also had significant systemic effects.
      The mice displayed increased mesangial cell proliferation in the kidney, frequent
      liver abnormalities, and marked alterations in plasma protein levels. Unlike
      previous studies where constitutive expression of exogenous IL-6 genes resulted
      in lymphoproliferative disorders characterized by massive plasmacytosis, minimal
      plasma cell expansion occurred in the MSCV-IL-6 mice during the observation
      period. Potential explanations for the differences in disease phenotypes observed
      in the present and previous studies are different cell types expressing the
      exogenous IL-6 genes, higher sustained circulating levels of IL-6 achieved using
      the MSCV-IL-6 retroviral delivery system, and/or the premature death (3-15 wk
      after transplantation) of the MSCV-IL-6 mice before the onset of plasmacytosis.
      This animal model should prove useful for further investigation of the function
      of IL-6 in normal and abnormal hematopoiesis and in inflammatory responses.

PMID- 1402660
TI  - Engineered humanized dimeric forms of IgG are more effective antibodies.
AB  - Humanized IgG1 M195 (HuG1-M195), a complementarity determining region-grafted
      recombinant monoclonal antibody, is reactive with CD33, an antigen expressed on
      myelogenous leukemia cells. M195 is in use in trials for the therapy of acute
      myelogenous leukemia. Since biological activity of IgG may depend, in part, on
      multimeric Fab and Fc clustering, homodimeric forms of HuG1-M195 were constructed
      by introducing a mutation in the gamma 1 chain CH3 region gene to change a serine
      to a cysteine, allowing interchain disulfide bond formation at the COOH terminal
      of the IgG. Despite similar avidity, the homodimeric IgG showed a dramatic
      improvement in the ability to internalize and retain radioisotope in target
      leukemia cells. Moreover, homodimers were 100-fold more potent at complement
      mediated leukemia cell killing and antibody-dependent cellular cytotoxicity using
      human effectors. Therefore, genetically engineered multimeric constructs of IgG
      may have advantages relative to those forms that are found naturally.

PMID- 1402662
TI  - Protection in simian immunodeficiency virus-vaccinated monkeys correlates with
      anti-HLA class I antibody response.
AB  - Our earlier reports demonstrated that Cynomolgus macaques vaccinated with either
      inactivated partially purified simian immunodeficiency virus (SIV), fixed SIV
      infected C8166 (a human T lymphoblastoid cell line) cells, or fixed uninfected
      C8166 cells can be protected against a challenge infection with the 32H isolate
      of SIVmac 251 (grown in C8166) (Stott, E. J., W. L. Chan, K. H. G. Mills, M.
      Page, F. Taffs, M. Cranage, P. Greenway, and P. Kitchin. 1990. Lancet. 336:1538;
      Stott, E. J., P. A. Kitchin, M. Page, B. Flanagan, L. F. Taffs, W. L. Chan, K. H.
      G. Mills, P. Silvera, and A. Rodgers. 1991. Nature [Lond.]. 353:393). Protection
      is correlated with the levels of antibody response to cellular antigens in the
      human cells from which the virus immunogen was grown. However, the mechanism of
      protection is unclear. We report here the analysis of sera from these protected
      monkeys and demonstrate that there is positive correlation of protection with
      antibody response to the HLA class I molecule.

PMID- 1402661
TI  - Stable expression of transdominant Rev protein in human T cells inhibits human
      immunodeficiency virus replication.
AB  - The human immunodeficiency virus (HIV) Rev protein is essential for viral
      structural protein expression (Gag, Pol, and Env) and, hence, for viral
      replication. In transient transfection assays, mutant forms of Rev have been
      identified that inhibit wild-type Rev activity and therefore suppress viral
      replication. To determine whether such transdominant Rev proteins could provide
      long-term protection against HIV infection without affecting T cell function, T
      leukemia cell lines were stably transduced with a retroviral vector encoding a
      transdominant mutant of the Rev protein, M10. While all the M10-expressing cell
      lines remained infectable by HIV-1, these same cells failed to support a
      productive replication cycle when infected with a cloned isolate of HIV-1. In
      addition, two out of three M10-expressing CEM clones were also resistant to
      highly productive infection by a heterogeneous HIV-1 pool. Expression of M10 did
      not affect induction of HIV transcription mediated by the kappa B regulatory
      element or Tat. Importantly, constitutive expression of Rev M10 did not alter the
      secretion of interleukin 2 in response to mitogen stimulation of EL-4 and Jurkat
      cells. The inhibition of HIV infection in cells stably expressing a transdominant
      Rev protein, in the absence of any deleterious effect on T cell function,
      suggests that such a strategy could provide a therapeutic effect in the T
      lymphocytes of acquired immunodeficiency syndrome patients.

PMID- 1402664
TI  - Cytokine gene expression in murine epidermal cell suspensions: interleukin 1 beta
      and macrophage inflammatory protein 1 alpha are selectively expressed in
      Langerhans cells but are differentially regulated in culture.
AB  - Epidermal Langerhans cells (LC) are considered direct yet immature precursors of
      dendritic cells (DC) in the draining lymph nodes. Although the development of LC
      into potent immunostimulatory DC occurs in vitro and has been studied in detail,
      little is known about their profile of cytokine gene expression. By using reverse
      transcriptase polymerase chain reaction analysis to screen 16 cytokines followed
      by Northern blotting for selected analysis, we determined the cytokine gene
      expression profile of murine LC at different time points in culture when T cell
      stimulatory activity is increasing profoundly. LC regularly expressed macrophage
      inflammatory proteins, MIP-1 alpha and MIP-2, and interleukin 1 beta (IL-1 beta).
      Both MIPs were downregulated upon culture and maturation into DC, whereas IL-1
      beta was strongly upregulated in culture. MIP-1 alpha and IL-1 beta mRNA were
      found only in LC, but not in other epidermal cells. Apart from trace amounts of
      IL-6 in cultured LC, several macrophage and T cell products were not detected.
      The cytokine expression profile of LC thus appears distinct from typical
      macrophages. The exact role of the cytokine genes we found transcribed in LC
      remains to be determined.

PMID- 1402663
TI  - Heavy chain variable (VH) region diversity generated by VH gene replacement in
      the progeny of a single precursor cell transformed with a temperature-sensitive
      mutant of Abelson murine leukemia virus.
AB  - Sequence analysis of a large number of DNA clones containing a functional heavy
      chain variable, diversity, and joining (VHDJH) complex generated by VH to VHDJH
      joining (VH gene replacement) in the progeny derived from a common precursor cell
      transformed with a temperature-sensitive (ts) Abelson murine leukemia virus (A
      MuLV) indicates that endogenous VH gene replacement in vitro generates
      immunoglobulin gene joints distinct from those generated by the usual VH to DJH
      joining. Such joints keep the pentamer CAAGA at the 3' end of the donor VH
      segment and lack a recognizable D segment, as can be seen also in vivo. The
      results suggest that VH gene replacement participates in generating VH region
      diversity in vivo, as previously postulated. During the joining process, a unique
      VH gene was selected in all progeny cells, together with a single A nucleotide
      dominantly added to the junctional boundaries. The basis of these regulatory
      processes is discussed.

PMID- 1402665
TI  - Bone marrow transplantation as a strategy for treatment of non-insulin-dependent
      diabetes mellitus in KK-Ay mice.
AB  - The effects of allogeneic bone marrow transplantation (BMT) on non-insulin
      dependent diabetes mellitus (NIDDM) were examined using KK-Ay mice. KK-Ay mice
      reconstituted with KK-Ay bone marrow cells showed glycosuria, hyperinsulinemia,
      and hyperlipidemia. However, KK-Ay mice (H-2b) that had been lethally irradiated
      (9.0 Gy) and then reconstituted with T cell-depleted bone marrow cells from
      normal BALB/c mice (H-2d) showed negative urine sugar with decreases in serum
      insulin and lipid levels 4 mo after BMT. Morphological recovery of islets and
      glomeruli was also noted after allogeneic BMT. These findings suggest that BMT
      can be used to treat not only a certain type of NIDDM but also its complications
      such as hyperlipidemia and diabetic nephropathy.

PMID- 1402666
TI  - A third tal-1 promoter is specifically used in human T cell leukemias.
AB  - A common feature of T cell acute lymphoblastic leukemias (T-ALLs) is the presence
      of structural alteration of the 5' part of the tal-1 locus, localized on
      chromosomal band 1p32. These alterations consist of either a t(1;14)(p32;q11)
      chromosomal translocation (3% of T-ALLs) or tald submicroscopic deletion (12-25%
      additional T-ALLs). We have characterized a case of T-ALL with t(1;14)(p32;q11)
      in which, unlike the majority of t(1;14), the recombination with the T cell
      receptor delta elements affected the 3' side of the tal-1 locus. In this case,
      tal-1 transcription is initiated from a promoter located within the fourth exon
      similarly to the DU 528 cell line. In a T-ALL bearing a t(1;14) affecting the 5'
      part of tal-1, two types of tal-1 transcripts were observed, namely those
      probably initiated from the D delta region juxtaposed to tal-1 by the
      translocation, and those from the exon 4 promoter. It is interesting that this
      exon 4 promotion was also found in leukemic T cell lines and T-ALL samples
      without apparent tal-1 genomic alteration. In contrast, no transcript initiated
      from the exon 4 promoter was found in T-ALL with tald1 or tald2 deletion. In
      these cells, tal-1 is expressed via SIL-tal-1 fused transcripts. Finally, this
      exon 4 initiation was detected neither in normal bone marrow, nor in malignant
      cells from the erythroid/megakaryocytic lineages. Taken as a whole, these data
      suggest that the exon 4 promoter is specifically active in T cell lineage.

PMID- 1402667
TI  - Immunoglobulin (Ig) mu, kappa transgenic mice express transgenic idiotype on
      endogenously rearranged IgM and IgA molecules by secretion of chimeric molecules.
AB  - The sera of C57BL/6 mice transgenic for a mu a allotype heavy (H) chain and kappa
      light chain gene contained endogenous nontransgene immunoglobulin (IgM) (mu b
      allotype) and IgA molecules which carried the idiotype expressed by the
      transgenically encoded IgM (mu a) molecule. Serological analysis demonstrated
      that the presence of the transgenic idiotype on endogenous IgM and IgA was caused
      by the secretion of chimeric molecules that carried both chains encoded by the mu
      a transgene and products of endogenously rearranged Ig mu b or alpha genes. These
      and other results suggest that allelic exclusion of Ig gene rearrangement in mu,
      kappa transgenic mice is not absolute, that B cells can secrete Igs composed of
      more than a single (H) chain type, and that endogenous isotype switching does not
      result in a complete silencing of transgene expression.

PMID- 1402668
TI  - A rat model of human T lymphocyte virus type I (HTLV-I) infection. 1. Humoral
      antibody response, provirus integration, and HTLV-I-associated
      myelopathy/tropical spastic paraparesis-like myelopathy in seronegative HTLV-I
      carrier rats.
AB  - Human T lymphocyte virus type I (HTLV-I) can be transmitted into several inbred
      strains of newborn and adult rats by inoculating newly established HTLV-I
      immortalized rat T cell lines or the human T cell line MT-2. The transmission
      efficiency exceeds 80%, regardless of strain differences or the age at
      transmission. The production of anti-HTLV-I antibodies significantly differs
      among the strains and depends on the age at the time of transmission. Rats
      neonatally inoculated with HTLV-I-positive rat or human cells generally become
      seronegative HTLV-I carriers throughout their lives, whereas adult rats
      inoculated with HTLV-I-positive cells at 16 wk of age become seropositive HTLV-I
      carriers. The HTLV-I provirus genome is present in almost all organs, regardless
      of whether the carriers are seronegative or seropositive. According to antibody
      titers to HTLV-I, there are three groups of inbred rat strains: ACI, F344, and
      SDJ (high responders); WKA, BUF, and LEJ (intermediate responders); and LEW (low
      responder). Three of three 16-mo-old seronegative HTLV-I carrier rats of the WKA
      strain developed spastic paraparesis of the hind legs. Neuropathological
      examinations revealed that the lesions were confined primarily to the lateral and
      anterior funiculi of the spinal cord. Both myelin and axons were extensively
      damaged in a symmetrical fashion, and infiltration with massive foamy macrophages
      was evident. The most severe lesions were at levels of the thoracic cord and
      continued from the cervical to the lumbar area. These histopathological features
      as well as clinical symptoms largely parallel findings in humans with HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). These HTLV-I
      carrier rats, in particular the WKA rats described above, can serve as a useful
      animal model for investigating virus-host interactions in the etiopathogenesis of
      HTLV-I-related immunological diseases, particularly HAM/TSP.

PMID- 1402669
TI  - Immunoglobulin M and D antigen receptors are both capable of mediating B
      lymphocyte activation, deletion, or anergy after interaction with specific
      antigen.
AB  - A series of immunoglobulin (Ig)-transgenic mice were generated to study the
      functional capabilities of the IgM and IgD classes of B lymphocyte antigen
      receptor in regulating both cellular development and responses to specific
      antigen. B cells from Ig-transgenic mice expressing either hen-egg lysozyme (HEL)
      specific IgM or IgD alone were compared with B cells from mice that coexpressed
      IgM and IgD of the same anti-HEL specificity. In all three types of Ig-transgenic
      mice, conventional B cells specific for HEL exhibited exclusion of endogenous Ig
      expression and matured to populate the usual microenvironments in peripheral
      lymphoid tissues. These peripheral B cells could be stimulated by HEL through
      either IgM or IgD antigen receptors to generate T cell dependent antibody
      production in vivo or to enhance T cell independent proliferative responses to
      lipopolysaccharide in vitro. Conversely, when HEL was encountered in vivo as a
      self-antigen, B cells expressing HEL-specific IgM or IgD alone were both rendered
      tolerant. In each case this occurred by clonal anergy in response to soluble
      autologous HEL, and clonal deletion when HEL was recognized as a membrane-bound
      self-antigen. Taken together, these findings indicate that IgM and IgD antigen
      receptors expressed alone on conventional B cells can support normal
      differentiation, antigen-dependent activation, and induction of self-tolerance,
      the only overt difference lying in a greater degree of receptor downregulation
      for IgM relative to IgD after induction of clonal anergy by soluble HEL.

PMID- 1402670
TI  - Triggering through CD16 or phorbol esters enhances adhesion of NK cells to
      laminin via very late antigen 6.
AB  - Very late antigens VLA-1, VLA-2, VLA-3, and VLA-6, belonging to the beta 1
      subfamily of integrins, have been identified as receptors for different binding
      domains of laminin (LM). We have detected VLA-6, but not VLA-1 and VLA-2 on a
      subset (50-70%) of fresh peripheral blood CD3-, CD16+, CD56+ human natural killer
      (NK) cells by immunofluorimetric and biochemical analysis. Binding assays
      performed on LM-coated plates showed that 10-15% of NK cells spontaneously adhere
      to LM, and this adhesion is mediated by VLA-6. Activation of NK cells through
      CD16 triggering or by phorbol ester results in a rapid increase of adhesion to
      LM, which is still mediated by VLA-6. The enhanced adhesiveness is not associated
      with changes in beta 1 LM receptor expression, while it correlates with changes
      in the phosphorylation status of alpha 6 subunit. The expression of VLA-6 on NK
      cells and the modulation of its avidity by activating stimuli may be relevant for
      NK cell migration and tissue location during inflammation or immune response.

PMID- 1402671
TI  - Tumor necrosis factor alpha is involved in mouse growth and lymphoid tissue
      development.
AB  - Tumor necrosis factor alpha (TNF-alpha), a major mediator of inflammation, also
      possesses a wide pleiotropism of actions, suggesting its involvement in
      physiological conditions. TNF-alpha mRNA is present in mouse embryonic tissues
      and also in fetal thymus and spleen. Repeated injections of a monospecific
      polyclonal rabbit anti-mouse TNF-alpha antibody in mice, starting either during
      pregnancy or at birth, led to a severe but transient growth retardation, already
      present at birth, reaching a 35% decrease in body weight at 3 wk, with complete
      recovery at 8 wk. The insulin growth factor I (IGF-I) blood levels were decreased
      to about 50%; growth hormone release and other endocrine functions were
      unaltered. A marked atrophy of the thymus, spleen, and lymph nodes was also
      observed, with lymphopenia and impaired development of T and B cell peripheral
      lymphoid structures. The pathways involving TNF-alpha in IGF-I release and early
      body growth are probably distinct from those by which TNF-alpha participates in
      early development of lymphoid tissues, where its low physiological release may
      contribute to enhance lymphoid cell expansion.

PMID- 1402672
TI  - Pseudo-high affinity interleukin 2 (IL-2) receptor lacks the third component that
      is essential for functional IL-2 binding and signaling.
AB  - Functional studies of the interleukin 2 receptor (IL-2R) of two (ED515-D and
      Kit225) IL-2-dependent and three (ED515-I, 3T3-alpha beta 11, and Hut102) IL-2
      independent cell lines were done. All of these cell lines appeared to express
      high as well as low affinity IL-2R. However, ED515-I and 3T3-alpha beta 11, which
      expressed the IL-2R beta chain, did not bind IL-2 at all when IL-2 binding to
      their IL-2R alpha chain was blocked with anti-Tac monoclonal antibody, whereas
      the intermediate affinity binding in ED515-D, Kit225, and Hut102 cells remained.
      We tentatively called the high affinity IL-2R of the former cells pseudo-high
      affinity IL-2R. The dissociation constant of pseudo-high affinity IL-2R was
      higher than that of ordinary high affinity IL-2R. Internalization of cell-bound
      125I-IL-2 into ED515-I and 3T3-alpha beta 11 cells was less efficient than that
      into ED515-D cells. The addition of IL-2 neither promoted cell growth nor
      upregulated IL-2R alpha chain expression in ED515-I and 3T3-alpha beta 11 cells.
      Furthermore, tyrosine phosphorylation of the cellular proteins (p120, p98, p96,
      p54, and p38) was induced or enhanced in response to the addition of IL-2 in
      ED515-D and Kit225 cells, but not in the cell lines expressing pseudo-high
      affinity IL-2R. Finally, 125I-IL-2 crosslinking followed by SDS-PAGE analysis
      showed an 80-kD band corresponding to p65 + IL-2, in addition to bands
      corresponding to IL-2R alpha and beta chain + IL-2 in cells bearing ordinary high
      affinity IL-2R but not in cells with pseudo-high affinity IL-2R. Taken together,
      we consider that another protein whose molecular mass is approximately 65 kD is
      functionally important in IL-2 binding and subsequent signal transduction and may
      be the third component of IL-2R.

PMID- 1402674
TI  - Generation of leukemia-reactive cytotoxic T lymphocyte clones from the HLA
      identical bone marrow donor of a patient with leukemia.
AB  - Allogeneic bone marrow transplantation (BMT) has been associated with a graft-vs.
      leukemia (GVL) reactivity. Since T cell depletion of the bone marrow graft has
      decreased the risk of graft-vs.-host disease (GVHD), but has been associated with
      higher rates of leukemia relapse, GVL reactivity is probably caused by donor
      derived T lymphocytes. Previously, we demonstrated that minor histocompatibility
      (mH) antigen-specific cytotoxic T lymphocyte (CTL) clones, generated from
      patients after BMT, are capable of major histocompatibility complex-(MHC)
      restricted lysis of (clonogenic) myeloid leukemic cells. Here, we investigated
      whether donor-derived leukemia-specific CTL clones can be generated in vitro,
      before BMT, using irradiated leukemic cells from a patient with acute myeloid
      leukemia as stimulator cells, and peripheral blood or bone marrow from the HLA
      genotypically identical sibling donor as responder cells. Several CTL lines were
      generated that showed specific lysis (> 50%) of the recipient leukemic cells in a
      51Cr-release assay. Two of these CTL lines were cloned by limiting dilution in
      the presence of the irradiated recipient cells. Multiple leukemia-reactive, HLA
      class I and II-restricted clones with various specificities could be established.
      These alloreactive, antileukemic CTL clones may cause GVL reactivity after BMT,
      and may be used as adjuvant immunotherapy in the treatment of leukemia.

PMID- 1402673
TI  - Antivirally protective cytotoxic T cell memory to lymphocytic choriomeningitis
      virus is governed by persisting antigen.
AB  - The basis of antiviral protection by memory cytotoxic T lymphocytes (CTL) was
      investigated in vivo and in vitro using lymphocytic choriomeningitis virus (LCMV)
      and recombinant vaccinia viruses expressing the LCMV-glycoprotein (vacc-GP) or 
      nucleoprotein (vacc-NP). The widely replicating LCMV with a tendency to persist
      induced solid long-term protective memory. The poorly replicating vaccinia
      recombinant viruses revealed in the vaccinated host that the antiviral capacity
      of the secondary immune T cell response and the protection against lethal LCM was
      dependent upon the immunizing antigen and its dose. Protection against lethal
      choriomeningitis is less sensitive to assess memory because it depends upon high
      levels of CTL precursors (p) and/or on an activated state of memory CTL. In
      contrast, antiviral protection measured as the capacity of the primed host to
      reduce virus titers after challenge infection correlated with elevated CTLp
      frequencies after immunization with live LCMV or recombinant vaccinia virus
      expressing the major LCMV epitope. CTLp frequencies were constantly increased up
      to 70 d for LCMV immune mice, but rapidly decreased a few weeks after
      immunization with low dose vaccinia recombinant virus. For example, mice primed
      with 2 x 10(6) plaque-forming units (PFU) of vacc-NP, or 2 x 10(2) PFU, or 2 x
      10(6) PFU of vacc-GP were antivirally protected on day 7 but not after day 30
      when CTLp could not be measured any longer in vitro. However, greater priming
      doses of vacc-NP (10(4) or 2 x 10(6) PFU) as well as LCMV (2 x 10(2) PFU) induced
      elevated levels of CTLp and antiviral protection for 60 d or longer. Adoptive
      transfer experiments of immune spleen cells into syngeneic recipients without
      addition of antigen demonstrated that maintenance of the antiviral protective
      capacity of the transferred cells depended on the presence of viral antigen.
      Thus, antiviral protection by memory CTL may be rather short-lived since it is
      based on activated T cells continuously stimulated by persisting antigen. This is
      best achieved by high immunizing antigen doses yielded either by widely
      replicating viruses or high doses of poorly replicating recombinant vaccines.

PMID- 1402675
TI  - Stimulation of mature unprimed CD8+ T cells by semiprofessional antigen
      presenting cells in vivo.
AB  - To test whether unprimed CD8+ cells can recognize class I alloantigens presented
      selectively on non-bone marrow (BM)-derived cells, unprimed parental strain CD8+
      cells were transferred to long-term parent-->F1 BM chimeras prepared with
      supralethal irradiation. Host class I expression in the chimeras was undetectable
      on BM-derived cells and, in spleen, was limited to low-level staining of vascular
      endothelium and moderate staining of follicular dendritic cells (a population of
      nonhemopoietic cells in germinal centers). Despite this restricted expression of
      antigen, acute blood-to-lymph recirculation of parental strain T cells through
      the chimeras led to selective trapping of 95% of CD8+ cells reactive to normal F1
      spleen antigen presenting cells (APC) in vitro. Subsequently, a small proportion
      of the trapped cells entered cell division and gave rise to effector cells
      expressing strong host-specific CTL activity. The activation of host-specific
      CD8+ cells was also prominent in double-irradiated chimeras, and cell separation
      studies showed that the effector cells were generated from resting precursor
      cells rather than from memory-phenotype cells. It is suggested that the non-BM
      derived cells in the chimeras acted as semiprofessional APC. These cells were
      nonimmunogenic for most host-reactive CD8+ cells but were capable of stimulating
      a small subset of high-affinity T cells. The possible relevance of the data to
      the prolonged immunogenicity of vascularized allografts in humans is discussed.

PMID- 1402676
TI  - Disruption of the SCL gene by a t(1;3) translocation in a patient with T cell
      acute lymphoblastic leukemia.
AB  - SCL gene disruptions are the most common chromosomal abnormality associated with
      the development of T cell acute lymphoblastic leukemia (ALL). Such disruptions
      can be the result of t(1;14) and t(1;7) translocations, as well as a
      cytogenetically undetectable interstitial deletion of chromosome 1. We present
      here a case of T cell ALL with a t(1;3)(p34;p21) translocation that also disrupts
      the SCL locus and leads to dysregulated SCL gene expression. This translocation,
      similar to previously reported SCL gene disruptions, appears to have been
      mediated, at least in part, by the V(D)J recombinase complex, since cryptic
      heptamer recognition sequences, as well as nontemplated N region nucleotide
      addition, are present at the breakpoints. The t(1;3) also disrupts a region on
      chromosome 3 characterized by alternating purine and pyrimidine residues, which
      can form a Z-DNA structure, reported to be prone to recombination events. A
      previously undescribed, evolutionarily conserved transcript unit is detected
      within 8 kb of the breakpoint on chromosome 3. This report extends the spectrum
      of recognized SCL translocations associated with T cell ALL, and underscores the
      contention that dysregulated SCL expression may be a causal event in T cell ALL.

PMID- 1402677
TI  - Plasmodium falciparum erythrocyte rosetting is mediated by promiscuous lectin
      like interactions.
AB  - Herein we describe an assay that was developed to quantitate the binding of
      normal red blood cells (RBC), labeled with carboxy fluorescein diacetate (C-FDA),
      to rosetting Plasmodium falciparum-infected RBC. The binding of RBC obtained from
      various animal species or humans to different strains or clones of rosetting P.
      falciparum-infected RBC was studied. A strain-specific preference of rosetting
      was observed for either blood group A/AB or B/AB RBC for all parasites tested.
      The higher affinity of rosette binding of blood group A, B, or AB vs. O RBC was
      reflected in larger rosettes when a given parasite was grown in RBC of the
      preferred blood group. The small size of the rosettes formed when P. falciparum
      was grown in blood group O RBC may be the in vitro correlate of the relative
      protection against cerebral malaria afforded by belonging to blood group O rather
      than to blood group A or B. Rosettes of a blood group A-preferring parasite could
      be completely disrupted by heparin only when grown in blood group O or B RBC, but
      not when grown in blood group A RBC. Similarly, the rosettes of a blood group B
      preferring parasite could be more easily disrupted by heparin when grown in blood
      group O or A RBC than when grown in blood group B RBC. Several different
      saccharides inhibited rosetting of group O RBC, including two monosaccharides
      that are basic components of heparin. The rosetting of the same parasites grown
      in blood group A or B RBC was less sensitive to heparin and was specifically
      inhibited only by the terminal mono- and trisaccharides of the A and the B blood
      group antigens, the H disaccharide, and fucose. Our results suggest that
      rosetting is mediated by multiple lectin-like interactions, the usage of which
      rely on the parasite phenotype and whether the receptors are present on the host
      cell or not.

PMID- 1402678
TI  - Interleukin 4 protects chronic lymphocytic leukemic B cells from death by
      apoptosis and upregulates Bcl-2 expression.
AB  - B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of
      slow-dividing and long-lived monoclonal B cells arrested at the intermediate
      stage of their differentiation. We previously showed that interleukin 4 (IL-4)
      not only inhibits but also prevents the proliferation of B-CLL cells. We report
      here that IL-4 protects the B-CLL cells from death by apoptosis (programmed cell
      death [PCD]). IL-4 inhibits spontaneous and hydrocortisone (HC)-induced PCD of
      highly purified B cells from 12 unselected CLL patients, as shown by sustained
      cell viability and lack of DNA fragmentation. IL-1, -2, -3, -5, -6, -7, tumor
      necrosis factor alpha, and transforming growth factor beta have no protective
      effect. The in vitro rescue from apoptosis by IL-4 is reflected by an increased
      expression of Bcl-2 protein, a proto-oncogene directly involved in the
      prolongation of cell survival in vivo and in vitro. Hence, IL-4-treated B-CLL
      cells express significantly more Bcl-2 than unstimulated, HC-treated, or fresh B
      CLL cells. Furthermore, subcutaneous injection of IL-4 into one CLL patient
      enhances Bcl-2 protein expression in the leukemic B cells. These data may suggest
      that IL-4 prevents apoptosis of B-CLL cells using a Bcl-2-dependent pathway.
      Given our recent observations that fresh T cells from B-CLL patients express IL-4
      mRNA, we propose that IL-4 has an essential role in the pathogenesis of CLL
      disease, by preventing both the death and the proliferation of the malignant B
      cells.

PMID- 1402679
TI  - Application of DNA amplification to pneumocystosis: presence of serum
      Pneumocystis carinii DNA during human and experimentally induced Pneumocystis
      carinii pneumonia.
AB  - Pneumocystis carinii pneumonia is a leading cause of morbidity and mortality in
      patients with the acquired immunodeficiency syndrome (AIDS). Much remains unknown
      about the basic biology of P. carinii and studies of this infection have been
      hampered by the lack of cultivation methods. We developed a sensitive and
      specific assay for P. carinii by utilizing DNA amplification of the P. carinii
      dihydrofolate reductase (DHFR) gene. By this method, P. carinii DNA was detected
      in the lungs of rats with experimentally induced P. carinii pneumonia 2 wk before
      the onset of histopathological changes. DNA amplification analysis of serum
      demonstrated that by 10 wk of corticosteroid treatment, 12 of 12 (100%) infected
      rats had circulating DHFR DNA. P. carinii DHFR DNA also was detected in the serum
      of patients with AIDS and active P. carinii pneumonia (12 of 14 sera collected
      prospectively). Patients with advanced AIDS but without a history of P. carinii
      pneumonia were negative by this assay (0 of 6 sera examined). Serum polymerase
      chain reaction may facilitate investigations into the natural history and
      epidemiology of P. carinii infection, provide insight into the pathogenesis of
      parasite dissemination, and offer a useful, noninvasive diagnostic test for the
      detection of human pneumocystosis.

PMID- 1402680
TI  - Development of autoimmune disease in SCID mice populated with long-term "in
      vitro" proliferating (NZB x NZW)F1 pre-B cells.
AB  - Pre-B cell lines proliferating for several months on stromal cells in the
      presence of interleukin 7 (IL-7) were established from fetal liver of (NZB x
      NZW)F1 mice. They express the B lineage-specific markers PB76, B220, and VpreB,
      but do not express surface immunoglobulin (sIg). Upon removal of IL-7 from the
      culture, they differentiate to sIg+ B cells that can then be stimulated by
      lipopolysaccharide to become IgM-secreting cells. Transfer of these pre-B cell
      lines into SCID mice leads to hypergammaglobulinemia of IgM (600-900
      micrograms/ml), IgG2a (1-3 mg/ml), and IgG3 (300-500 micrograms/ml) for the next
      3-5 mo. The spleen appears populated with (NZB x NZW)F1-derived pre-B cells, few
      B cells, and many IgM and/or IgG-producing plasma cells. In contrast, SCID mice
      populated with pre-B cell lines of normal (C57BL/6 x DBA/2)F1 mouse fetal liver
      develop normal levels of serum IgM (approximately 100-300 micrograms/ml), almost
      no detectable levels of IgG, and no plasma cell hyperplasia. The (NZB x NZW)F1
      pre-B cell-populated SCID mice contain elevated serum titers of IgG antinuclear
      autoantibodies, but no retroviral gp70-specific nor erythrocyte-specific
      autoantibodies. Up to 20% of the SCID mice develop proteinuria as a consequence
      of IgG deposits in the kidney glomeruli during a 7-mo period of observation. All
      signs of autoimmune disease seen in these mice are independent of the sex of the
      SCID host. This experimental system provides a distinction between the disease
      determining (NZB x NZW)F1 genes, which are expressed in the B lymphocyte lineage
      and cause the development of the disease, from those expressed in other cell
      lineages which only modulate its progression.

PMID- 1402681
TI  - Peripheral engraftment of fetal intestine into athymic mice sponsors T cell
      development: direct evidence for thymopoietic function of murine small intestine.
AB  - Adult athymic, lethally irradiated, F1-->parent bone marrow-reconstituted (AT x
      BM) mice were engrafted bilaterally with day 16-18 fetal intestine or fetal
      thymus into the kidney capsule and were studied for evidence of peripheral T cell
      repopulation of 1-12 wk postengraftment. Throughout that time period, both types
      of grafts were macroscopically and histologically characteristic of
      differentiated thymus or intestine tissues, respectively. Beginning at week 2
      postengraftment, clusters of lymphocytes were present within intestine grafts,
      particularly in subepithelial regions and in areas below villus crypts. As
      determined by immunofluorescence staining and flow cytometric analyses,
      lymphocytes from spleen and lymph nodes of sham-engrafted mice (AT x BM-SHAM)
      were essentially void of T cells, whereas in AT x BM thymus-engrafted (AT x BM
      THG) mice, which served as a positive control for T cell repopulation, normal
      levels of T cells were present in spleen and lymph nodes by week 3
      postengraftment, and at times thereafter. Most striking, however, was the finding
      that T cell repopulation of the spleen and lymph nodes occurred in AT x BM fetal
      intestine-engrafted (AT x BM-FIG) mice beginning 3 wk postengraftment. Based on H
      2 expression, peripheral T cells in AT x BM-FIG mice were of donor bone marrow
      origin, and consisted of CD3+, T cell receptor (TCR)-alpha/beta+ T cells with
      both CD4+8- and CD4-8+ subsets. Peripheral T cells in AT x BM-FIG mice were
      functionally mature, as demonstrated by their capacity to proliferate after
      stimulation of CD3 epsilon. Moreover, alloreactive cytotoxic T lymphocytes were
      generated in primary in vitro cultures of spleen cells from AT x BM-FIG and AT x
      BM-THG mice, though not in spleen cell cultures from AT x BM-SHAM mice.
      Histologic studies of engrafted tissues 3-4 wk postengraftment demonstrated that
      thymus leukemia (Tl) antigens were expressed on epithelial surfaces of intestine
      grafts, and that both TCR-alpha/beta+ and TCR-gamma/delta+ lymphocytes were
      present in intestine grafts. Collectively, these findings indicate that the
      murine small intestine has the capacity to initiate and regulate T cell
      development from bone marrow precursors, thus providing a mechanism by which
      extrathymic development of intestine lymphocytes occur.

PMID- 1402682
TI  - Expression of vascular permeability factor (vascular endothelial growth factor)
      by epidermal keratinocytes during wound healing.
AB  - Persistent microvascular hyperpermeability to plasma proteins even after the
      cessation of injury is a characteristic but poorly understood feature of normal
      wound healing. It results in extravasation of fibrinogen that clots to form
      fibrin, which serves as a provisional matrix and promotes angiogenesis and scar
      formation. We present evidence indicating that vascular permeability factor (VPF;
      also known as vascular endothelial growth factor) may be responsible for the
      hyperpermeable state, as well as the angiogenesis, that are characteristic of
      healing wounds. Hyperpermeable blood vessels were identified in healing split
      thickness guinea pig and rat punch biopsy skin wounds by their capacity to
      extravasate circulating macromolecular tracers (colloidal carbon, fluoresceinated
      dextran). Vascular permeability was maximal at 2-3 d, but persisted as late as 7
      d after wounding. Leaky vessels were found initially at the wound edges and later
      in the subepidermal granulation tissue as keratinocytes migrated to cover the
      denuded wound surface. Angiogenesis was also prominent within this 7-d interval.
      In situ hybridization revealed that greatly increased amounts of VPF mRNA were
      expressed by keratinocytes, initially those at the wound edge, and, at later
      intervals, keratinocytes that migrated to cover the wound surface; occasional
      mononuclear cells also expressed VPF mRNA. Secreted VPF was detected by
      immunofluoroassay of medium from cultured human keratinocytes. These data
      identify keratinocytes as an important source of VPF gene transcript and protein,
      correlate VPF expression with persistent vascular hyperpermeability and
      angiogenesis, and suggest that VPF is an important cytokine in wound healing.

PMID- 1402683
TI  - Interleukin 4 is localized to and released by human mast cells.
AB  - Recent attention has focused on the T helper type 2 (Th2) lymphocyte as a source
      of interleukin 4 (IL-4) in allergic disease. However, Th2 cells themselves
      require a pulse of IL-4 to initiate this synthesis. Here we provide
      immunohistochemical evidence of IL-4 localization to human mast cells of the skin
      and respiratory tract, and demonstrate that immunoglobulin E-dependent
      stimulation of purified human lung mast cells leads to the rapid release of IL-4
      into the extracellular environment. We propose that mast cell activation in an
      allergic response provides a rapid and local pulse of IL-4 into the local
      environment essential for the triggering of T lymphocytes into sustained IL-4
      production and to initiate inflammatory cell accumulation and activation.

PMID- 1402684
TI  - N region diversity of a transgenic substrate in fetal and adult lymphoid cells.
AB  - The rearrangement of immunoglobulin (Ig) and T cell receptor (TCR) genes requires
      the activity of an as yet undefined V(D)J recombinase. One component of the
      recombinase appears to be a terminal transferase which may be involved in the
      addition of untemplated nucleotides (N regions) to the V(D)J joints. It has been
      observed that rearranged Ig and TCR genes isolated from fetal liver have few if
      any N regions, whereas in the adult mouse, these genes have a large number of
      untemplated nucleotides. The presence of N regions greatly alters the composition
      of the third hypervariable, complementarity determining region of the respective
      proteins, thus playing a major role in the conformation of the binding site. It
      was possible that, for functional reasons, N region-containing Ig and TCR genes
      were not permissible at the fetal stage of development. We have produced
      transgenic mice with a rearrangement test gene which, after V-J recombination,
      does not result in the production of functional Ig or TCR proteins. We report
      here that the rearrangement products have no N regions in fetal liver, but that
      the majority of joints in adult lymphoid tissues have N additions. The study is
      also an interesting demonstration of the randomness of rearrangements and the
      enormous variability that can be created from a single pair of V and J sequences.

PMID- 1402686
TI  - Gemfibrozil enhances the listeriacidal effects of fluoroquinolone antibiotics in
      J774 macrophages.
AB  - J774 macrophage-like cells express organic anion transporters that promote the
      efflux of fluoroquinolone antibiotics such as norfloxacin (NFX) from these cells.
      Gemfibrozil (GFZ) blocks organic anion transport in J774 cells, thereby
      facilitating the intracellular accumulation of NFX (Cao, C., H.C. Neu, and S.C.
      Silverstein. 1991. J. Cell Biol. 115:467a [Abstr.]). To determine whether GFZ
      enhances the efficacy of fluoroquinolone antibiotics against intracellular
      bacterial pathogens, J774 cells were infected with Listeria monocytogenes and
      incubated in medium containing a fluoroquinolone antibiotic in the presence or
      absence of GFZ. Intracellular growth of L. monocytogenes was evaluated by lysing
      J774 cells and assaying for colony-forming units of Listeria. GFZ intensified the
      bacteriostatic effect of 4 micrograms/ml NFX and rendered 8 micrograms/ml
      bactericidal for L. monocytogenes. GFZ had a similar potentiating effect when
      used in combination with 2 micrograms/ml ciprofloxacin (CFX). CFX plus GFZ was
      bactericidal for intracellular L. monocytogenes. Treatment of J774 cells with NFX
      plus GFZ markedly reduced the cytotoxic effect of the bacteria on these cells.
      Over 55% of cells treated with 8 micrograms/ml NFX alone were dead 16 h after
      infection, whereas only 5% of cells treated with 8 micrograms/ml NFX plus GFZ
      were dead at 16 h. Similarly, GFZ potentiated the ability of 2 micrograms/ml to
      protect J774 cells against the cytocidal effect of Listeria. NFX in combination
      with GFZ limited cell-to-cell spread of L. monocytogenes. In antibiotic-free
      medium, > 99% of J774 cells contained intracellular L. monocytogenes at 14 h
      after infection. NFX alone in the medium did not change this outcome. However, 4
      micrograms/ml NFX plus GFZ decreased bacterial spread by approximately 40% at 24
      h postinfection, and 8 micrograms/ml NFX plus GFZ prevented all spread beyond the
      initially infected cell population. These results suggest that GFZ could be used
      clinically to enhance the efficacy of fluoroquinolone and of other anionic
      antibiotics against bacteria that grow and/or reside within macrophages and/or
      other cells.

PMID- 1402685
TI  - Inhibition or activation of human T cell receptor transfectants is controlled by
      defined, soluble antigen arrays.
AB  - We present evidence that direct T cell receptor (TCR) occupancy by antigen can
      either activate or inhibit T cells, depending upon whether or not a threshold
      number of local TCRs are crosslinked by multivalent arrays of the antigen.
      Variants of Jurkat cells were previously transfected with TCR alpha and beta
      chains that bind fluorescein, yielding FL-TCR+ human T cells. The transfectants
      are activated upon binding soluble multivalent antigen arrays at concentrations
      well below those required for monovalent interactions. This activation, measured
      by calcium fluxes and interleukin 2 (IL-2) production, indicates the superior
      binding avidity of multivalent ligands. Smaller, less multivalent arrays do not
      activate the cells, but antagonize larger arrays, demonstrating that antigen can
      bind TCR as either agonist or antagonist. The balance between activation and
      inhibition depends upon antigen array size, ligand valence, and concentration,
      indicating that a threshold extent of receptor crosslinking, and not individual
      perturbations of single TCR, is required for activation by antigen. Approximately
      100 stimulatory arrays specifically bind per FL-TCR+ cell at concentrations where
      IL-2 production is half-maximal.

PMID- 1402687
TI  - Activin A/erythroid differentiation factor is induced during human monocyte
      activation.
AB  - Activin A/erythroid differentiation factor (EDF), a dimeric polypeptide hormone
      composed of two beta A subunits, regulates growth and erythroid differentiation
      of human hematopoietic progenitor and erythroleukemia cells. We have identified
      activated human peripheral blood monocytes as a natural source of activin A/EDF.
      In these cells, lipopolysaccharide (LPS) induced rapidly the expression of the
      beta A subunit mRNAs through protein kinase C-dependent transcriptional
      regulation. The beta A subunit mRNA expression was also increased by 1,25
      dihydroxyvitamin D3, an inducer of macrophage maturation of monocytes. Western
      analysis with an anti-beta A antibody and an erythroid differentiation bioassay
      confirmed that the conditioned media of LPS-activated monocytes contained the
      activin A/EDF protein. We suggest that monocyte/macrophage-derived activin A/EDF
      may not only modulate hematopoiesis but may also act as a mediator molecule in
      the diverse physiologic and pathogenetic events in which these cells are
      involved.

PMID- 1402688
TI  - A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T
      lymphocytes directed against tumor antigen MZ2-E.
AB  - We have reported the identification of human gene MAGE-1, which directs the
      expression of an antigen recognized on a melanoma by autologous cytolytic T
      lymphocytes (CTL). We show here that CTL directed against this antigen, which was
      named MZ2-E, recognize a nonapeptide encoded by the third exon of gene MAGE-1.
      The CTL also recognize this peptide when it is presented by mouse cells
      transfected with an HLA-A1 gene, confirming the association of antigen MZ2-E with
      the HLA-A1 molecule. Other members of the MAGE gene family do not code for the
      same peptide, suggesting that only MAGE-1 produces the antigen recognized by the
      anti-MZ2-E CTL. Our results open the possibility of immunizing HLA-A1 patients
      whose tumor expresses MAGE-1 either with the antigenic peptide or with autologous
      antigen-presenting cells pulsed with the peptide.

PMID- 1402689
TI  - CD4 expression is differentially required for deletion of MLS-1a-reactive T
      cells.
AB  - Clonal deletion of thymocytes expressing potentially self-reactive T cell
      receptors (TCRs) occurs during thymocyte ontogeny. Mice deficient for CD4
      expression provide a unique model system to study the contribution of the CD4
      molecule in negative selection of T cells reactive against the major
      histocompatibility complex class II-associated retroviral self-superantigen, Mls
      1a. In the presence of Mls-1a determinants, mature CD8+ T cells expressing V beta
      6, 8.1, and 9 were deleted in CD4-deficient mice, thus demonstrating that TCR
      affinity for Mls-1a is sufficient for deletion and that a signal through CD4 was
      not required. However, in instances where the TCR affinity for Mls-1a is low, as
      in the case of V beta 7+ T cells, CD4 expression was required for clonal
      deletion. These results demonstrate that for Mls-1a-mediated clonal deletion of T
      cells, the requirement for the accessory or coreceptor function of CD4 depends on
      the affinity of the TCR.

PMID- 1402690
TI  - Reactivation of a major histocompatibility complex class II gene in mouse
      plasmacytoma cells and mouse T cells.
AB  - Terminally differentiated plasma cells and mouse T cells do not express major
      histocompatibility complex (MHC) class II genes although class II gene expression
      is observed in pre-B and mature B cells as well as in activated human T cells.
      Transient heterokaryons were prepared and analyzed to investigate the mechanisms
      of inactivation of MHC class II gene in mouse plasmacytoma cells and mouse T
      cells. The endogenous MHC class II genes in both mouse plasmacytoma cells and
      mouse T cells can be reactivated by factors present in B cells. This reactivation
      of class II gene is also observed by fusion with a human T cell line which
      expresses MHC class II genes, but not with a class II negative human T cell line.
      It appears that the loss of MHC class II gene expression during the terminal
      differentiation of B cells or T cell lineage is due to absence of positive
      regulatory factor(s) necessary for class II transcription.

PMID- 1402691
TI  - Characterization and cloning of a novel glycoprotein expressed by stromal cells
      in T-dependent areas of peripheral lymphoid tissues.
AB  - A novel glycoprotein (gp) expressed by stromal cells of peripheral lymphoid
      tissue has been characterized immunohistochemically, biochemically, and at the
      molecular level. This molecule, gp38, was identified with a monoclonal antibody
      (mAb) (clone 8.1.1) previously shown to react with a subpopulation of thymic
      epithelium. This mAb generated a reticular labeling pattern in medullary and
      paracortical areas of lymph nodes and in splenic white pulp. At the
      ultrastructural level, labeling by the 8.1.1 mAb was restricted to fibroblastic
      reticular stromal cells. Serial sections of lymph node and spleen labeled with
      anti-CD3, anti-B220, and 8.1.1 mAbs clearly showed that the 8.1.1+ cells were
      associated with T cell-dependent areas. In severe combined immunodeficiency
      (SCID) or Nu/Nu mice, splenic white pulp also exhibited reticular labeling with
      the 8.1.1 mAb in the absence of detectable numbers of T cells, indicating that
      the appearance of 8.1.1-reactive stromal cells in discrete areas of peripheral
      lymphoid tissue was T cell independent. The cDNA encoding this stromal cell
      molecule was cloned by direct expression in COS cells and found to encode a 172
      amino acid sequence with the typical features of a type I integral membrane
      protein. COS cells transfected with the gp38 clone direct the expression of an
      approximately 38-kD protein that reacts with the 8.1.1 mAb but not with isotype
      matched controls. Comparison of the predicted amino acid sequence of 8.1.1 mAb
      but not with isotype-matched controls. Comparison of the predicted amino acid
      sequence of 8.1.1 with proteins in the National Biomedical Research Foundation
      (NBRF) data base showed that gp38 is very closely related to the early response
      protein OTS-8 obtained from a cDNA library of tumor promoting agent (TPA)-induced
      murine osteoblastic cell line, MC3T3-E1.

PMID- 1402692
TI  - Primacy and recency effects in nonhuman primates.
AB  - The reports of primacy and recency memory effects in nonhuman primates have been
      criticized because they have all used an initiating response. That is, the
      presentation of the to-be-remembered list of items was always contingent on a
      response being initiated by the nonhuman primate. It has been argued that this
      initiating response improves performance for early items in the list, resulting
      in the occurrence of the primacy effect, independent of any memory processing
      mechanism. This criticism was addressed in the present study by not using an
      initiating response prior to the presentation of the list. Nevertheless, both a
      primacy and a recency effect were observed in all 6 rhesus monkeys evaluated
      using a serial probe recognition task. Thus, the results are similar to those for
      humans, in that both primacy and recency effects can be obtained in nonhuman
      primates. A brief literature review is included, and it is proposed that the
      primacy and recency effects observed in humans, nonhuman primates, and
      infraprimates can be explained within the context of the configural-association
      theory.

PMID- 1402693
TI  - Choice behavior in transition: development of preference with ratio and interval
      schedules.
AB  - In Experiment 1, the choice responses of 8 pigeons were observed during 50
      periods of transition. Each condition began with equal probabilities of
      reinforcement on 2 response keys and switched to unequal probabilities. With the
      ratio of the 2 probabilities held constant, preference for the higher probability
      developed more rapidly when the 2 probabilities were high than when they were
      low. In Experiment 2, each condition began with 2 equal variable-interval
      schedules, but later 1 key delivered 60%, 75%, or 90% of the reinforcers. The
      rate of approach to asymptotic performance was roughly the same with all 3
      reinforcement percentages. These and previous results pose difficulties for some
      well-known models of acquisition, but the results are well described by a simple
      model that states that the strength of each response is independently increased
      by reinforcement and decreased by nonreinforcement.

PMID- 1402694
TI  - Effects of discrimination training on responding during a compound conditioned
      stimulus.
AB  - Four experiments examined responding in the presence of a triple-element compound
      ABC after discrimination training in which 2 compounds, AB and BC, signaled the
      delivery of food and 1 element alone, B, signaled the absence of food. In
      Experiments 1 and 2, using rats, responding during ABC was more vigorous than in
      a control group for which A and C but not B had been individually paired with
      food. This finding was replicated in Experiment 3, which used pigeons, and in
      Experiment 4, where all 3 stimuli of the control condition were individually
      paired with food. The results are more consistent with a configural than with an
      elemental theory of learning.

PMID- 1402695
TI  - Discrimination of contour-deleted images by pigeons.
AB  - Three experiments attempted to determine which properties of pictorial
      representations of objects control their discrimination by pigeons. A particular
      focus was whether the representation mediating such discriminations could be
      described by the simple viewpoint-invariant primitive volumes of Biederman's
      (1987) recognition-by-components theory of object recognition or by Cerella's
      (1990) particulate features. In all 3 experiments, pigeons were first trained to
      discriminate drawings of 4 stimulus objects with half of the contour deleted but
      with the component geons postulated by Biederman's theory recoverable.
      Discrimination accuracy was then compared for test items containing the original
      particulate features, affording the retrieval of the original component geons, or
      having neither of these properties of the training stimuli. Although response
      accuracy was significantly greater when the component geons of the original
      objects were retrievable, measurable control over recognition by the particulate
      features of the objects and by their specific locations was also found. The
      results are consistent with the idea of component geon recognition as one of the
      important factors in object discrimination.

PMID- 1402696
TI  - Associative regulation of Pavlovian fear conditioning: unconditional stimulus
      intensity, incentive shifts, and latent inhibition.
AB  - Conditional stimuli (CS) associated with painful unconditional stimuli (US)
      produce a naloxone-reversible analgesia. The analgesia serves as a negative
      feedback regulation of fear conditioning that can account for the impact of US
      intensity and CS predictiveness on Pavlovian fear conditioning. In Experiment 1
      training under naloxone produced learning curves that approached the same high
      asymptote despite US intensity. Shifting drug treatment during acquisition had
      effects that paralleled US intensity shifts. In Experiment 3 naloxone reversed
      Hall-Pearce (1979) negative transfer using a contextual CS, indicating that
      conditional analgesia acquired during the CS-weak-footshock phase retards
      acquisition in the CS-strong-footshock phase. Experiment 5 used a tone CS in both
      a latent-inhibition and a negative-transfer procedure. Only negative transfer was
      blocked by naloxone. Therefore, negative transfer but not latent inhibition is
      mediated by a reduction of US processing.

PMID- 1402697
TI  - Theoretical concepts and strategies for understanding perceptual-motor skill:
      from information capacity in closed systems to self-organization in open,
      nonequilibrium systems.

PMID- 1402699
TI  - The 'superstition' experiment: a reversible figure.

PMID- 1402698
TI  - The information capacity of the human motor system in controlling the amplitude
      of movement. 1954.

PMID- 1402700
TI  - 'Superstition' in the pigeon. 1948.

PMID- 1402701
TI  - Measuring recognition memory.
AB  - Recent years have seen an expanded interest in recognition memory tasks. This
      resurgence of interest has also renewed concerns with measurement problems.
      Comparing 4 models of recognition memory, Snodgrass and Corwin (1988) found that
      measures of bias from the distribution-free (nonparametric) model were
      inadequate. However, their analysis was based on bias measures that can be shown
      a priori to be nonindependent of discrimination. This article traces the history
      of the nonparametric model and develops a better measure of bias. The consequence
      of developing this better measure is that the nonparametric model deserves
      serious consideration.

PMID- 1402702
TI  - Similarity-scaling studies of dot-pattern classification and recognition.
AB  - Classification performance in the dot-pattern, prototype-distortion paradigm
      (e.g., Posner & Keele, 1968) was modeled within a multidimensional scaling (MDS)
      framework. MDS solutions were derived for sets of dot patterns that were
      generated from prototypes. These MDS solutions were then used in conjunction with
      exemplar, prototype, and combined models to predict classification and
      recognition performance. Across 3 experiments, an MDS-based exemplar model
      accounted for the effects of several fundamental learning variables, including
      level of distortion of the patterns, category size, delay of transfer phase, and
      item frequency. Most important, the model quantitatively predicted classification
      probabilities for individual dot patterns in the sets, not simply general trends
      of performance. There was little evidence for the existence of a prototype
      abstraction process that operated above and beyond pure exemplar-based
      generalization.

PMID- 1402703
TI  - Comparative assessment of psychomotor performance: target prediction by humans
      and macaques (Macaca mulatta).
AB  - Although nonhuman primates such as rhesus monkeys (Macaca mulatta) have been
      useful models of many aspects of cognition and performance, it has been argued
      that, unlike humans, they may lack the capacity to respond as predictor
      operators. Data from the present series of experiments undermine this claim,
      suggesting instead a continuity of predictive competency between humans and
      nonhuman primates. A prediction coefficient was devised to examine the degree to
      which each subject's response path approximated the optimal predictive strategy.
      Whereas human subjects (N = 30) generally predicted more accurately, rhesus
      monkeys (N = 10) also significantly anticipated the movements of the target in
      all conditions. It appears that humans and rhesus monkeys both exhibit the
      capacity to respond to where a stimulus is going.

PMID- 1402705
TI  - The use of indirect memory tests to assess malingered amnesia: a study of
      metamemory.
AB  - Many techniques have been suggested for identifying criminal suspects who are
      simulating amnesia for the events surrounding a crime. The present research
      focuses on indirect memory tests as a potential means of discriminating between
      those who genuinely suffer from amnesia and those who are simulating. Subjects
      studied a list of words and subsequently performed either a word completion or a
      fragment completion task. Under normal indirect test instructions, typical
      priming effects were observed. When subjects were motivated to simulate amnesia
      for the list, target completion rates were consistently, and sometimes reliably,
      below baseline completion rates. This finding is contrary to the performance of
      genuine amnesics, whose performance on indirect tests typically mirrors that of
      normal subjects. Indirect tests may prove useful in discriminating genuine and
      simulating amnesics.

PMID- 1402706
TI  - Selectivity, scope, and simplicity of models: a lesson from fitting judgments of
      perceived depth.
AB  - When comparing psychological models a researcher should assess their relative
      selectivity, scope, and simplicity. The third of these considerations can be
      measured by the models' parameter counts or equation length, the second by their
      ability to fit random data, and the first by their differential ability to fit
      patterned data over random data. These conclusions are based on exploration of
      integration models reflecting depth judgments. Replication of Massaro's (1988a)
      results revealed an additive model (Bruno & Cutting, 1988), and Massaro's fuzzy
      logical model of perception (FLMP) fit data equally well, but further exploration
      showed that the FLMP fit random data better. The FLMP's successes may reflect not
      its sensitivity in capturing psychological process but its scope in fitting any
      data and its complexity as measured by equation length.

PMID- 1402704
TI  - Memory for day of the week: a 5 + 2 day cycle.
AB  - People use a variety of schemes to keep track of time. One such scheme is the
      week, with its 7 distinctly named days. This article examines memory for day of
      the week and its relation to memory for time of day and for elapsed time (number
      of days). Data are presented from a study in which people answered a set of
      interview questions about the time of occurrence of a particular event. Two
      issues are addressed. The first issue concerns the way different temporal schemes
      are organized in relation to each other in memory. Memory for day of the week is
      independent of other aspects of temporal memory. The second issue concerns
      whether the week is organized hierarchically into either weekday periods or
      weekend periods or both. The weekday period forms a distinct 5-day unit within
      the 7-day weekly cycle. The present data, together with those from the authors'
      earlier work, suggest that the time an event occurred is encoded in relation to a
      set of separate temporal scripts (e.g., daily and weekly) and that such scripts
      may be hierarchically organized.

PMID- 1402707
TI  - The picture superiority effect in categorization: visual or semantic?
AB  - Two experiments are reported whose aim was to replicate and generalize the
      results presented by Snodgrass and McCullough (1986) on the effect of visual
      similarity in the categorization process. For pictures, Snodgrass and
      McCullough's results were replicated because Ss took longer to discriminate
      elements from 2 categories when they were visually similar than when they were
      visually dissimilar. However, unlike Snodgrass and McCullough, an analogous
      increase was also observed for word stimuli. The pattern of results obtained here
      can be explained most parsimoniously with reference to the effect of semantic
      similarity, or semantic and visual relatedness, rather than to visual similarity
      alone.

PMID- 1402708
TI  - Serial pattern learning by event observation.
AB  - Serial pattern learning was investigated in a variation of the task introduced by
      Nissen and Bullemer (1987). We presented an asterisk at 1 of 4 spatial locations
      on each trial, and Ss either responded with a keypress or observed the event. The
      first 4 blocks contained 10 repetitions of a 10- or 16-element pattern, and the
      5th block contained a random sequence. The difference in response time on the 5th
      random block and the previous patterned block served as an indirect measure of
      pattern learning. A direct measure was obtained in a final test block in which Ss
      predicted the next asterisk position. Equivalent learning occurred for responding
      and observing with indirect measures, but observation was superior with direct
      measures. These findings indicate that knowledge of serial order can develop
      through simple perceptual experience, and this is more available to deliberate
      recall than is knowledge acquired while responding.

PMID- 1402709
TI  - Framing and conflict: aspiration level contingency, the status quo, and current
      theories of risky choice.
AB  - The effect of positive versus negative frames on risky choice was examined for a
      variety of scenarios and risks. Preferences in the positive domain were strong
      and mainly risk averse, with notable exceptions. Preferences in the negative
      domain, however, were marked by their inconsistency, shown both by an
      overwhelming lack of significant majority preferences and a surprisingly strong
      tendency of individual subjects to vacillate in their negatively framed choices
      across presentations. This finding is accounted for by a proposed aspiration
      level contingency in which aspiration levels are systematically set to be more
      difficult to achieve in the face of a perceived loss than a gain. The
      implications of the results, and the aspiration level contingency, are explored
      with respect to current theories of risky choice, including Kahneman and
      Tversky's (1979) prospect theory and Lopes's (1987, 1990) security
      potential/aspiration theory.

PMID- 1402710
TI  - Time course of movement planning: selection of handgrips for object manipulation.
AB  - A goal of research on the cognitive control of movement is to determine how
      movements are chosen when many movements are possible. We addressed this issue by
      studying how subjects reached for a bar to be moved as quickly as possible from a
      home location to a target location. Ss generally grabbed the bar in a way that
      afforded a comfortable posture at the target location (the end-state comfort
      effect) and with the thumb toward the end of the bar that would be aligned with
      the target (the thumb-toward bias). The data suggested that subjects chose
      handgrips by retrieving instances of previous reaches, not by carrying out
      computations that treated candidate reaches as new behavioral events.

PMID- 1402711
TI  - Cue familiarity but not target retrievability enhances feeling-of-knowing
      judgments.
AB  - Two hypotheses concerning people's ability to predict later memory performance
      for unrecalled items were investigated. The target retrievability hypothesis
      states that feeling-of-knowing judgments (FKJs) are based on partial target
      information; and the cue familiarity hypothesis asserts that they are based on
      recognition of the cues. In Experiments 1 and 2, subjects either generated or
      read the targets of paired associates. Half of the cues had been primed in a
      pleasantness-rating task. The generation manipulation increased recall but had no
      effect on FKJs. Cue priming had no effect on recall but increased FKJs. In
      Experiment 3, using general information questions, primed after the initial
      recall attempt, both cue and target priming increased FKJs. Experiment 4, which
      remedied difficulties in Experiment 3, showed no effect of target priming whereas
      cue priming increased FKJs. The results favor the cue familiarity hypothesis.

PMID- 1402712
TI  - Mental animation: inferring motion from static displays of mechanical systems.
AB  - Reaction-time and eye-fixation data are analyzed to investigate how people infer
      the kinematics of simple mechanical systems (pulley systems) from diagrams
      showing their static configuration. It is proposed that this mental animation
      process involves decomposing the representation of a pulley system into smaller
      units corresponding to the machine components and animating these components in a
      sequence corresponding to the causal sequence of events in the machine's
      operation. Although it is possible for people to make inferences against the
      chain of causality in the machine, these inferences are more difficult, and
      people have a preference for inferences in the direction of causality. The mental
      animation process reflects both capacity limitations and limitations of
      mechanical knowledge.

PMID- 1402713
TI  - Relational properties and memory-based category construction.
AB  - Although many experiments have investigated factors that constrain perceptual
      category construction, there have been no investigations of factors that
      constrain memory-based (MB) category construction. Six experiments examined the
      extent to which perceptual and MB sorting were influenced by correlated
      dimensions, family resemblance principles, and conceptual knowledge. Sensitivity
      to many types of relational information (e.g., correlated features, causal
      relations, interactive properties of objects, and family resemblance relations)
      was observed with perceptual sorting, but these properties were rarely used to
      organize information in MB sorting conditions. Instead, there was a clear
      preference to organize categories around single dimensions. Even when perfectly
      correlated features were causally related, Ss in memory conditions did not use
      correlations to construct categories. The strengths and limitations of MB
      analyses and categorizations are discussed.

PMID- 1402714
TI  - Evaluating hypnotic memory enhancement (hypermnesia and reminiscence) using
      multitrial forced recall.
AB  - Two experiments investigated whether hypnosis enhances memory retrieval per se or
      merely increases a person's willingness to report recollections. Both experiments
      assessed immediate and delayed (i.e., 1 week) recall for pictorial stimuli. In
      Experiment 1, following an initial waking baseline recall, subjects of high or
      low hypnotic ability completed a series of recall trials conducted either in
      hypnosis or in the walking condition. The classic hypermnesia effect was
      obtained, but with no supplemental contribution of hypnosis. In Experiment 2,
      hypnosis was introduced only after 6 waking-recall trials. Hypnosis again failed
      to enhance retrieval of new correct items, although it increased the production
      of new incorrect recall among hypnotizable individuals. The findings provide no
      evidence for alleged hypermnesic properties of hypnosis.

PMID- 1402715
TI  - Shapes of reaction-time distributions and shapes of learning curves: a test of
      the instance theory of automaticity.
AB  - The instance theory assumes that automatic performance is based on single-step
      direct-access retrieval from memory of prior solutions to present problems. The
      theory predicts that the shape of the learning curve depends on the shape of the
      distribution of retrieval times. One can deduce from the fundamental assumptions
      of the theory that (1) the entire distribution of reaction times, not just the
      mean, will decrease as a power function of practice; (2) asymptotically, the
      retrieval-time distribution must be a Weibull distribution; and (3) the exponent
      of the Weibull, which is the parameter that determines its shape, must be the
      reciprocal of the exponent of the power function. These predictions were tested
      and mostly confirmed in 12 data sets from 2 experiments. The ability of the
      instance theory to predict the power law is contrasted with the ability of other
      theories to account for it.

PMID- 1402716
TI  - Auditory priming: implicit and explicit memory for words and voices.
AB  - Five experiments explore priming effects on auditory identification and
      completion tasks as a function of semantic and nonsemantic encoding tasks and
      whether speaker's voice is same or different at study and test. Auditory priming
      was either unaffected by the study task manipulation (Experiments 2, 4, and 5) or
      was less affected than was explicit memory (Experiments 1 and 3). Study-to-test
      changes of speaker's voice had nonsignificant effects on priming when white noise
      masked target items on the identification test (Experiments 1 and 2) or the stem
      completion test (Experiment 5). However, significant voice change effects were
      observed on priming of completion performance when stems were spoken clearly
      (Experiments 3 and 4). Results are consistent with the idea that a presemantic
      auditory perceptual representation system plays an important role in the observed
      priming. Alternative explanations of the presence or absence of voice change
      effects under different task conditions are considered.

PMID- 1402717
TI  - Short-term memory for the timing of auditory and visual signals.
AB  - Short-term memory for the timing of irregular sequences of signals has been said
      to be more accurate when the signals are auditory than when they are visual. No
      support for this contention was obtained when the signals were beeps versus
      flashes (Experiments 1 and 3) nor when they were sets of spoken versus
      typewritten digits (Experiments 4 and 5). On the other hand, support was obtained
      both for beeps versus flashes (Experiments 2 and 5) and for repetitions of a
      single spoken digit versus repetitions of a single typewritten digit (Experiment
      6) when the subjects silently mouthed a nominally irrelevant item during sequence
      presentation. Also, the timing of sequences of auditory signals, whether verbal
      (Experiment 7) or nonverbal (Experiments 8 and 9), was more accurately remembered
      when the signals within each sequence were identical. The findings are considered
      from a functional perspective.

PMID- 1402718
TI  - The remembering of auditory event durations.
AB  - Three experiments examined the incidental remembering of event durations. In each
      study, Ss engaged in an initial learning phase in which they performed a set of
      perceptual ratings on events for a varying number of trials. These events
      consisted of tonal sequences or ecological sounds that varied in their internal
      structure and ending. Ss were then given a surprise memory task in which they
      were asked to recognize the duration of each event (Experiments 1 and 3) or
      extrapolate its completion (Experiment 2). Results showed that in contrast to
      irregularly timed events, those filled with regularly timed or continuous pitch
      information yielded high levels of accuracy that increased with greater learning
      experience. In addition, durations marked by a nonarbitrary ending were more
      accurately remembered than those marked by an arbitrary ending which, in fact,
      were misremembered as shorter than their actual duration. These findings are
      discussed in terms of an approach that emphasizes the role of event structure on
      perceiving and remembering activities.

PMID- 1402719
TI  - Individual differences in working memory and comprehension: a test of four
      hypotheses.
AB  - A relationship has consistently been found between measures of working memory and
      reading comprehension. Four hypotheses for this relationship were tested in 3
      experiments. In the first 2 experiments, a moving window procedure was used to
      present the operation-word and reading span tasks. High- and low-span subjects
      did not differentially trade off time on the elements of the tasks and the to-be
      remembered word. Furthermore, the correlation between span and comprehension was
      undiminished when the viewing times were partialed out. Experiment 3 compared a
      traditional experimenter-paced simple word-span and a subject-paced span in their
      relationship with comprehension. The experimenter-paced word-span correlated with
      comprehension but the subject-paced span did not. The results of all 3
      experiments support a general capacity explanation for the relationship between
      working memory and comprehension.

PMID- 1402720
TI  - Persistence of negative priming: II. Evidence for episodic trace retrieval.
AB  - Responses to recently ignored stimuli may be slower or less accurate than to new
      stimuli. This negative priming effect decays over time when delay is randomized
      within subjects, but not when delay varies between subjects. In Experiment 1,
      response-stimulus intervals (RSI) of 500 and 4,000 ms were randomized within
      subjects in a target localization task. Negative priming of ignored locations
      diminished with longer delay. However, no significant decay was obtained when RSI
      and the preceding RSI were equal. Similar results were obtained when RSI and
      preceding RSI were deliberately confounded by blocking (Experiment 2). Negative
      priming appears to depend on temporal discriminability of the priming episode.

PMID- 1402721
TI  - Asymptomatic prostate nodules.

PMID- 1402722
TI  - Asymptomatic prostate nodules.

PMID- 1402723
TI  - Asymptomatic prostate nodules.

PMID- 1402724
TI  - Physician anger.

PMID- 1402725
TI  - Improving prevention in primary care: physicians, patients, and process.

PMID- 1402726
TI  - Tools, teamwork, and tenacity: an office system for cancer prevention.
AB  - BACKGROUND: Despite national priorities in cancer control, the number of people
      with established ongoing medical care who do not receive indicated preventive
      services is substantial. Proven strategies to optimize preventive care in
      community practice are limited. METHODS: In the Cancer Prevention in Community
      Practice Project (CPCP), 50 primary care providers were randomly assigned to
      receive an "office system" intervention. The intervention led to reorganization
      of office operations based on four functional core components: identifying
      patients' needs for services; monitoring their status over time; providing
      positive reinforcement to patients; and establishing an internal feedback
      component consisting of a brief audit to assess how the system is operating.
      Implementation of the CPCP system in each practice was accomplished using trained
      facilitators, and involved incorporating one or more tools developed to meet the
      functional components of the practice. RESULTS: One hundred percent of the
      practices were successful in implementing some changes in their office operations
      that met CPCP office system functional criteria. All study practices implemented
      customized flow sheets, while use of other office system tools were incorporated
      at between 32% to 75% of study sites. Identifying patients in need of preventive
      services was performed most often by the clinical staff (39%), whereas monitoring
      patients' receipt of preventive services over time and reinforcing positive
      patient behavior were performed most often by physicians (63% and 46%,
      respectively). Changes made in practices were maintained for at least 12 months.
      CONCLUSIONS: Primary care practices in community settings can implement
      significant and lasting changes in their practice environment that will improve
      their performance of preventive activities. The functional components of the CPCP
      office system design proposed and tested here are applicable to a wide variety of
      practice settings.

PMID- 1402727
TI  - Anabolic steroid use among adolescents in a rural state.
AB  - BACKGROUND: Anabolic-androgenic steroid use is an increasing problem among high
      school students. Previous reports have been mainly from metropolitan areas.
      METHODS: We report the first study of anabolic-androgenic steroid use to
      concentrate on rural communities. The study was conducted using an anonymous
      survey of a random sample of male high school students (N = 3900) in grades 10
      through 12 encompassing 31 high schools in a predominantly rural state. RESULTS:
      Two-hundred five (5.3%) students reported using steroids. The prevalence of
      illicit drug use was significantly higher (P < .05) in steroid users (74%) than
      in nonusers (31%) (P < .001). The association was between anabolic-androgenic
      steroid use and illicit drug use rather than between sports participation of any
      type and illicit drug use (P > .2). Comparison of the prevalence of illicit drug
      use among athletic (63.2%) and nonathletic (36.8%) steroid users found no
      significant difference. Findings were similar with cigarette use. There was no
      difference in the rate of steroid use by school enrollment (69 to 1495) or by
      city population size (< 200 to 64,000). The predominant reason for steroid use
      was to improve appearance (43%). CONCLUSIONS: This study found the prevalence of
      steroid use throughout a predominantly rural state to be similar to that found by
      previous studies conducted in metropolitan areas; prevalence was not affected by
      city or school size. Steroid use was closely associated with illicit drug and
      cigarette use, a new finding that deserves further examination.

PMID- 1402728
TI  - Determinants of delayed pregnancy testing among adolescents.
AB  - BACKGROUND: Pregnant teenagers often prolong the interval between suspecting and
      confirming that they are pregnant. Prior studies suggest a number of potential
      determinants for this delay but do not specify which ones are most salient.
      METHODS: In a cross-sectional survey, 123 pregnant teenagers, 64 of whom
      maintained their pregnancies and 59 of whom had abortions, completed a short
      version of the Center for Epidemiologic Studies Depression Scale, the Family
      APGAR test, and a study-specific questionnaire. RESULTS: Significant bivariate
      determinants of delayed pregnancy testing included young maternal age, black
      race, lower educational attainment, lack of pregnancy symptoms, continuing the
      pregnancy, and denial. Only denial, however, retained a significant net effect on
      delayed testing (P < .05) when the effects of these six variables were modeled
      using multiple linear regression. CONCLUSIONS: These results suggest that
      psychological barriers are the most salient determinants of delayed pregnancy
      testing among the teenagers surveyed in this study. Some teenagers may not
      volunteer information about a suspected pregnancy. Providers, therefore, should
      directly question teenagers about sexual activity and discuss the importance of
      early testing when pregnancy is suspected. Findings also suggest further research
      that would increase understanding of adolescent health behavior in pregnancy and
      identify effective clinical and educational interventions.

PMID- 1402729
TI  - Comparative validity of two hearing loss screening questionnaires.
AB  - BACKGROUND: Hearing loss is one of the most common of all physical impairments,
      but physicians seldom screen adults for it, and patients often overlook or deny
      hearing problems. This study was designed to validate the use of two self
      administered hearing loss questionnaires. METHODS: Two self-administered
      screening questionnaires and a hearing screening evaluation using the Welch Allyn
      Audioscope 3 instrument were given to 409 consecutive family practice patients
      over the age of 18 years. Correlational, discriminate, sensitivity, and
      specificity analyses were conducted on the data. RESULTS: Neither of the existing
      questionnaires was clinically sensitive enough to be recommended for use. A new
      tool based on a discriminate function analysis of the existing questionnaires was
      developed. In contrast, the audioscope proved to be a sensitive screening tool.
      Of those patients who were identified, 88% did not follow recommendations to
      obtain further evaluation. CONCLUSIONS: Existing self-administered questionnaires
      cannot be recommended for use. A controlled clinical study using the newly
      derived questionnaire, the Smith Hearing Screening, should be conducted.

PMID- 1402730
TI  - Attitudes toward and experience in research among family medicine chairs.
AB  - BACKGROUND: Productive research environments are important for the development of
      academic family medicine, yet many of the current family medicine chairs have had
      little research training or experience and have rated research skills as a low
      priority for themselves. The younger chairs, however, representing the next
      generation of academic leadership, may have more traditional academic values,
      including the promotion of research. METHODS: The 106 active and interim chairs
      of family medicine academic units were surveyed by mail to determine their
      characteristics and attitudes toward their work responsibilities. We compared
      chairs 50 years of age or younger with those over 50 years of age. RESULTS:
      Before attaining their positions, younger chairs, in general, were more likely
      than older chairs to have received formal training in management, patient care,
      and academic skills, but they shared similar work experiences. Specifically,
      younger chairs were more likely to have had formal research training but did not
      have a great deal more research experience. Younger chairs were more likely to
      consider research skills to be essential in their present work activities and to
      identify faculty with formal training and extensive experience in research as
      potential chair replacements. CONCLUSIONS: Younger chairs appear to have a
      greater appreciation for the importance of research, having received more formal
      training and valuing research skills in themselves and potential replacements.
      With the impending large turnover in family medicine leadership, there will be an
      opportunity to recruit chair replacements with similar viewpoints toward
      research, thus improving the outlook for research in academic family medicine.

PMID- 1402731
TI  - Diagnosis of acute pelvic pain.
AB  - The diagnosis of acute pelvic pain in the woman of reproductive age represents a
      major clinical challenge. In approaching such a patient, the clinician must
      differentiate between pregnancy-related causes, gynecologic disorders, and
      nonreproductive tract causes. A careful history and physical examination, along
      with selective and knowledgeable use of diagnostic tests and procedures, are
      essential to the diagnostic process. Diagnostic laparoscopy represents the
      reference standard for diagnosis of many of its possible causes and can obviate
      the need for exploratory laparotomy. Once competing diagnoses have been
      adequately excluded, an empiric trial of antibiotic therapy for acute pelvic
      inflammatory disease, coupled with close clinical follow-up, should be considered
      in patients with acute pelvic pain found to have cervical motion tenderness and
      bilateral adnexal tenderness on examination.

PMID- 1402732
TI  - Coding and reimbursement of primary care biopsy and destruction procedures.
AB  - Current medical practice requires physicians to accurately report services
      provided to patients. Billing for destruction of benign and malignant lesions and
      for surgical, needle, and endoscopic biopsy procedures involves the selection of
      specific 1992 Current Procedural Terminology (CPT) codes. Payment for these
      procedures by third-party payers often requires the International Classification
      of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) coding for neoplastic
      lesions. This review explains the proper codes to use in identifying common
      biopsy and destruction procedures performed by primary care physicians. The
      Health Care Financing Administration's relative value units and one state's
      published Medicaid payment rates are included for each procedure code.
      Instructions for selecting site-specific biopsy and destruction codes are
      provided.

PMID- 1402733
TI  - Acute leukostasis pulmonary distress syndrome.
AB  - A 75-year-old woman in accelerated-phase chronic myeloid leukemia with
      hyperleukocytosis presented with acute respiratory distress syndrome. Despite
      early and aggressive pulmonary support and cytoreductive chemotherapy, the
      patient died. Autopsy confirmed the presence of the leukostasis syndrome. The
      clinical, radiologic, pathophysiologic, and therapeutic aspects of this entity
      are reviewed.

PMID- 1402734
TI  - Hyperemesis, hyperthyroidism, or both?
AB  - Nausea and vomiting are common during pregnancy and, when severe enough to
      require intervention, may develop into the syndrome known as hyperemesis
      gravidarum. When the diagnosis of hyperemesis is considered, a careful search for
      secondary causes is necessary. The list of secondary causes includes
      hyperthyroidism, a relatively uncommon condition during pregnancy. Because many
      of the signs and symptoms of hyperthyroidism are common, and thyroid function
      tests are more difficult to interpret during normal pregnancy, making the
      diagnosis of hyperemesis gravidarum is a challenge. The decision to treat or to
      await spontaneous resolution depends on the severity of the illness and the
      likelihood of the presence of true Graves' disease. The case summarized here
      demonstrates these issues, and includes treatment options for hyperemesis
      associated hyperthyroidism.

PMID- 1402736
TI  - Osmotic and ionic regulation during hypoxia in the medicinal leech, Hirudo
      medicinalis L.
AB  - The concentrations of inorganic and organic ions and osmolality in the blood of
      the medicinal leech, Hirudo medicinalis, were determined during normoxia and
      hypercapnic and hypocapnic hypoxia. In normoxic animals, the blood sodium
      concentration was 124.5 +/- 4.2 mmol/l and the total cation concentration was
      132.2 +/- 4.3 mEq/l (mean +/- S.D.). Major anionic compounds were chloride (40.8
      +/- 1.6 mmol/l), bicarbonate (8.4 +/- 1.3 mmol/l), and organic anions (42.5 +/-
      2.3 mEq/l). Among the latter, malate accounts for 30.4 +/- 2.2 mEq/l. The nature
      of the remaining anion fraction, which balances cation and anion concentrations
      in leech blood, remains unknown. Within 96 h of hypercapnic hypoxia, the amount
      of organic osmolytes in leech tissue increased from the control level of 56.6 +/-
      9.1 to 158.3 +/- 19.5 mumol/g dry weight. An even higher amount of organic acids
      was accumulated within 96 h of hypocapnic hypoxia (218.0 +/- 53.7 mumol/g dry
      weight). A possible reason for this is that lactate, which is a major end-product
      of hypocapnic hypoxia, cannot be excreted to the external medium as easily as
      propionate. The accumulation of blood organic acids generating osmotic stress in
      the animals was compensated by an equimolar decrease in sodium and chloride ion
      concentrations. In hypercapnic animals these changes resulted in a constant
      osmotic concentration of the blood (200 mosmol/kg H2O) during the experimental
      period. Between 24 and 96 h of hypocapnic hypoxia, however, the increase in the
      osmotic gradient between animal and medium was correlated with further net water
      uptake and the obvious deterioration of the volume- and ion-regulatory mechanisms
      in these animals.

PMID- 1402735
TI  - Putting teeth into your physical exam: Part 1. Children and adolesccents.

PMID- 1402737
TI  - Signal transduction by calcium and protein kinase C during egg activation.

PMID- 1402739
TI  - Epibolic extension of the presumptive ectodermal layer of embryos of the newt
      Cynops pyrrhogaster before and during gastrulation.
AB  - Epibolic extension of the presumptive ectodermal layer (PEL) was investigated in
      embryos of the newt Cynops pyrrhogaster before and during gastrulation. The PEL
      was composed of only one layer of columnar cells at all stages examined. The
      cells of the PEL became elongated from the blastula to the early gastrula stage.
      They were most elongated at the early gastrula stage and then shortened during
      gastrulation. Present observations suggest that changes in cell shape of the PEL
      play an important role in the control of the epibolic extension of the newt
      embryos. The morphology and movement of the isolated cells from the PEL were
      examined in an attempt to elucidate the role of cell movement in epibolic
      extension of the PEL. Blebbing and vermiform cells which showed active cell
      movement appeared at the early blastula stage. The blebbing cells, which formed
      large hyaline blebs that moved around the circumference of each cell, appeared in
      large numbers at the early blastula stage. The frequency of the blebbing cells
      decreased from the early blastula to the early gastrula stage and increased again
      during gastrulation. The vermiform cells, which had an elongated cell body and
      moved in a worm-like manner, increased in frequency from the early blastula to
      the early gastrula stage. The relative number of such vermiform cells was maximal
      at the early gastrula stage and decreased abruptly during gastrulation. These
      results suggest that the elongation of the cells of the PEL is controlled by the
      active cell movement which resembles that of a worm.

PMID- 1402738
TI  - Mouse limb bud cells respond to retinoic acid in vitro with reduced growth.
AB  - Retinoic acid (RA) has dramatic effects on the pattern of developing and
      regenerating vertebrate limbs. These effects are considered to result from RA
      induced changes in the positional identity of limb cells, and involve the
      formation of extra structures. Whether the growth required to form the
      supernumerary parts of the pattern is a primary effect of RA treatment or a
      secondary effect that follows after a change in positional identity is not at
      present known. In this paper we have investigated the effects of RA treatment on
      the growth of cells from anterior and posterior halves of mouse limb buds in
      vitro. We observed that under our culture conditions, limb bud cells treated with
      1 nM to 1 microM RA (0.3 ng/ml to 300 ng/ml) continue to grow but do so at a
      significantly slower rate than control cultures. There is a maximum inhibition of
      growth (50% of controls) between 10 nM and 100 nM RA, which corresponds to the
      measured range of concentrations of RA in vivo. Our observation of a significant
      decrease in growth rate over a wide range of RA concentrations is consistent with
      comparable reports of growth inhibition for a large number of other cell types in
      vitro as well as with the observation that exogenous RA inhibits blastemal growth
      in amphibians during the period of exposure to RA. We propose that the effects of
      RA on growth, either enhancement in vivo or reduction in vitro, can be seen as
      consequences of the ability of RA to alter positional identity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1402740
TI  - Retinoic acid respecifies limb bud cells in vitro.
AB  - Retinoic acid (RA) is known to have dramatic effects on limb pattern formation
      and has been shown to exert its effects on limbs by converting anterior limb bud
      cells into cells with posterior positional properties. In this study we find that
      dissociated posterior limb bud cells from chick and mouse embryos cultured at
      high density (micromass cultures) are able to stimulate the formation of
      supernumerary digits when grafted into developing wing buds and that the
      positional identity of both chick and mouse limb bud cells can be maintained for
      finite periods of time in vitro. Furthermore, using this assay system we have
      tested whether anterior cells from mouse and chick limb buds can be converted
      into cells with posterior identity by exposure to RA in vitro. We find that
      anterior limb bud cells acquire posterior properties after culture in the
      presence of RA.

PMID- 1402741
TI  - Body temperature rhythm of the tree shrew, Tupaia belangeri.
AB  - The circadian rhythm of body temperature of the tree shrew Tupaia belangeri was
      studied by telemetry. The amplitude of the daily (or circadian) variation was
      found to be much larger than that of most endotherms (amplitude approximately 5
      degrees C) and the bimodal shape of the rhythm differed from the cosine waveform
      that characterizes the temperature rhythms of most other species. In free-running
      conditions, as well as in the entrained state, the temperature rhythm remained
      synchronized to the rhythm of locomotor activity.

PMID- 1402742
TI  - Micromanipulation of cleaved embryos cultured in protein-free medium: a mouse
      model for assisted hatching.
AB  - A mouse model for studying anomalies of human embryonic hatching following
      micromanipulation is proposed. Initiation and completion of mouse blastocyst
      hatching was severely impaired (34/292; 12% and 28/292; 10%, respectively) with
      protein deprivation, resembling the situation in human in vitro fertilization.
      Hatching ability was restored when an artificial gap was introduced in the zona
      pellucida by micromanipulation at the cleaved embryo stage. This enabled 77%
      (285/371) and 36% (134/371) of the embryos to initiate and complete hatching in
      protein-free medium. No differences were found in overall cell counts between the
      two groups of embryos. Transfer of micromanipulated blastocysts to pseudopregnant
      females resulted in development of healthy fetuses.

PMID- 1402743
TI  - Remains identification by frontal sinus radiographs.

PMID- 1402744
TI  - Remains identification by frontal sinus radiographs.

PMID- 1402745
TI  - Determining total method level of detection and level of quantitation for breath
      alcohol analysis programs.

PMID- 1402746
TI  - Determination of the concentration of tetramethylenedisulfotetramine in human
      blood by GC/FPD.

PMID- 1402747
TI  - Hyoid fracture and strangulation.
AB  - Observation of hyoid fracture in skeletonized remains offers potentially valuable
      information on the history of the skeleton or evidence of foul play, or both.
      Perimortem hyoid fracture frequently indicates manual strangulation, although
      ligature strangulation, hanging, and other forms of trauma to the neck cannot be
      ruled out without additional evidence. Such fractures are rare in children and
      infants, since the hyoid components are not fully ossified and are more flexible
      than in adults. Both antemortem and postmortem origins of the fractures must also
      be considered.

PMID- 1402748
TI  - Estimation of adult stature from fragmentary tibias.
AB  - Linear-regression equations derived from measurements of tibial condyles from 100
      individuals in the Hamann-Todd Collection retrodicted known stature with a level
      of confidence comparable to many of the existing stature-estimation techniques.
      Statures of an independent control group were estimated with similar success. The
      strong linear relationship that exists between the length of the tibia and the
      size of the condyles allows adult stature (of American whites and blacks) to be
      estimated from the proximal tibia. Since complete tibial length is not required,
      this technique could prove useful in forensic science and archaeological cases
      where less-than-intact elements are recovered.

PMID- 1402749
TI  - Modification of the Trotter and Gleser female stature estimation formulae.
AB  - Stature-estimation formulae in common use are those of Trotter and Gleser. Their
      formulae for females are based on Terry collection skeletons. These skeletons are
      from people who died in the early 1990s. Because there has been considerable
      change in body size since then, it is possible that the Trotter and Gleser
      formulae are inappropriate for modern forensic-science application. The Trotter
      and Gleser female formulae are tested using data from the Forensic Data Bank at
      the University of Tennessee. For whites, the femur and tibia yield stature
      estimates differing from one another by about 3 cm. Using femur and tibia lengths
      from modern forensic cases and modern height data from anthropometric surveys,
      new regression intercepts are calculated for Trotter and Gleser's female
      formulae. The new intercepts improve the performance of the formulae on modern
      individuals. The Trotter and Gleser formulae for black females require no
      adjustment. Both blacks and whites have experienced a secular increase in bone
      length, but whites have experienced a change in proportions as well.

PMID- 1402750
TI  - Time since death determinations of human cadavers using soil solution.
AB  - This study was conducted to collect data on specific volatile fatty acids
      (produced from soft tissue decomposition) and various anions and cations
      (liberated from soft tissue and bone), deposited in soil solution underneath
      decomposing human cadavers as an aid in determining the "time since death." Seven
      nude subjects (two black males, a white female and four white males) were placed
      within a decay research facility at various times of the year and allowed to
      decompose naturally. Data were amassed every three days in the spring and summer,
      and weekly in the fall and winter. Analyses of the data reveal distinct patterns
      in the soil solution for volatile fatty acids during soft tissue decomposition
      and for specific anions and cations once skeletonized, when based on accumulated
      degree days. Decompositional rates were also obtained, providing valuable
      information for estimating the "maximum time since death." Melanin concentrations
      observed in soil solution during this study also yields information directed at
      discerning racial affinities. Application of these data can significantly enhance
      "time since death" determinations currently in use.

PMID- 1402751
TI  - Surveillance of human immunodeficiency virus (HIV) antibodies in medicolegal
      autopsies in Finland--monitoring early changes in HIV-seropositivity among risk
      groups and average population.
AB  - In order to cooperate with voluntary screening programs aimed at the surveillance
      of the HIV epidemic in Finland, we have studied medicolegal autopsies for HIV
      antibodies since 1986 using an enzyme immunoassay on postmortem sera. The
      investigation covered 47.4% and 39.2%, respectively, of all deaths under the age
      of 65 years in the metropolitan areas of Helsinki and Turku--two cities on the
      densely populated southern coast of Finland from which most HIV infections have
      thus far been detected. Nine HIV-positive cases (0.12%) were detected among the
      7305 medicolegal autopsies tested in 1986 to 1990. This figure is higher than the
      prevalence of 0.01 to 0.03% in voluntary screening programs for the general
      population would suggest. Seven of our cases had previously tested positive, and
      two were previously unknown cases, indicating that people at high risk are
      clustered in the medicolegal autopsy series. Of the six cases in an early stage
      of infection, three committed suicide suggesting the importance of HIV-screening
      in suicide cases in tracing symptomless HIV carriers. Five of the cases were
      detected in 1990, a year when the number of new HIV infections had more than
      doubled compared to the previous two years. This suggests that testing of
      medicolegal autopsies as surrogate tests for the population gives useful
      information even in low-prevalence areas like Finland. Such testing has none of
      the ethical problems of many other back-up surveys, and may be particularly
      sensitive to early changes in epidemiology.

PMID- 1402752
TI  - ABO genotyping by polymerase chain reaction.
AB  - ABO blood group system's genotyping by polymerase chain reaction in genomic DNA
      level is developed. The positions of nucleotide 258 and 700 of cDNA from A
      transferase were used to distinguish A, B, and O alleles by restriction enzyme
      digestion. To identify the 258th nucleotide, a 199- or 200-bp DNA fragment was
      amplified by PCR and digested with Kpn I. For the 700th nucleotide, a 128-bp PCR
      amplified fragment was designed and digested with Alu I. By examining the DNA
      fragment digested patterns, ABO genotypes were easily determined. Results
      obtained using this method on 20 ABO-known peripheral blood samples showed that
      this new technique could provide accurate ABO genotype. Biologic forensic
      samples, such as, blood stains, saliva stains, semen stains, hair, bone tissue,
      and semen contaminated with vaginal secretion were also successfully typed. This
      rapid, sensitive and reliable method should be applicable not only in forensic
      identification but also in medical examination.

PMID- 1402754
TI  - A psychiatric study of persons charged with arson.
AB  - A total of 29 court-referred individuals charged with arson were psychiatrically
      studied. From this pre-trial cohort from a large heterogeneous urban population
      base, a higher rate of psychosis was found than in other recent studies. However,
      consistent with these studies was the rarity of the diagnosis of pyromania. An
      important finding of this study was the substantial number of fires set by
      individuals who are homeless mentally disordered or substance abusing, or both.

PMID- 1402753
TI  - Robotic method for the analysis of morphine and codeine in urine.
AB  - A totally automated procedure has been developed for the detection and
      quantitation of morphine and codeine in urine case samples. The samples were
      initially screened for these drugs by a Syva EMIT Toxicology System (ETS). A
      Zymate laboratory robotic system confirms positive samples from Syva ETS by
      performing the hydrolysis, extraction, and derivatization of morphine and
      codeine. The derivatized morphine and codeine were detected using gas
      chromatography/mass spectrometry (GC/MS). Enzymatic hydrolysis conditions were
      experimentally optimized during method development. The automation of these
      procedures has proven to be reliable and efficient.

PMID- 1402755
TI  - Criminals' explanations of their criminal behavior, Part I: The contribution of
      criminologic variables.
AB  - The author reviewed the literature concerning criminals' explanations of their
      crimes and then studied the explanations given by 100 incarcerated men. He found
      no significant associations between juvenile or adult arrest histories, alias
      use, age at time of the crime, trial plea, sentence length, duration of
      incarceration, and explanation types used. Only murderers significantly used a
      specific explanation type. These observations suggest that explanations are
      largely independent of traditional criminological attributes; that prolonged
      confinement to prison does not result in offenders admitting to their crimes;
      and, that killers have an especially difficult time accepting responsibility for
      taking the life of another human being.

PMID- 1402756
TI  - Criminals' explanations of their criminal behavior, Part II: A possible role for
      psychopathy.
AB  - The author reviewed the literature concerning the effect of criminals' current
      psychopathology on their explanations about their crimes. He then studied 100
      incarcerated men, examining the associations between their explanations and
      various historically documented aspects of psychopathy. Previously and
      independently documented patterns of pathological lying, lack of remorse or
      guilt, callousness or lack of empathy, and failure to accept responsibility for
      their own behavior were significantly associated with the offenders not admitting
      responsibility for their crimes. Further, independently described histories of
      pathological lying were associated with criminals' blaming their convictions on a
      faculty criminal-justice system, while histories of failure to accept
      responsibility for their behavior were associated with blaming someone else for
      their index crimes.

PMID- 1402757
TI  - Postmortem stability of lung surfactant phospholipids.
AB  - The postmortem stability of the main phospholipids of lung surfactant
      phosphatidyl choline (PC), phosphatidyl ethanolamine (PE), phosphatidyl inositol
      (PI), phosphatidyl serine (PS) and sphingomyelin (S) in three different deaths;
      one caused by fresh-water drowning, one by salt-water drowning, and one from a
      sodium-pentobarbital overdose has been studied. The drug overdose was considered
      the control because there was no surfactant involvement. The results show the
      stability of these kinds of lipids in the first 24 h, with a progressive decrease
      from 48 h on until 96 h, with a significant correlation to the time of P less
      than 0.01 in most cases.

PMID- 1402758
TI  - Postmortem angiography of catheter-induced pulmonary artery perforation.
AB  - A case of pulmonary artery perforation by the placement of a balloon-tipped, flow
      directed (Swan-Ganz) catheter, as demonstrated postmortem by angiography and
      confirmed by conventional autopsy method, is reported. Angiography is an
      effective adjunctive modality in the postmortem diagnosis and localization of
      pulmonary artery perforation. In cases of suspected catheter-induced pulmonary
      artery perforation and death, postmortem angiography may prove useful to the
      forensic pathologist.

PMID- 1402759
TI  - Toxicologic findings in the USS Iowa disaster.
AB  - The toxicologic results from the 47 victims of the explosion on the USS Iowa are
      presented. Good correlation between carboxyhemoglobin saturations and cause of
      death was found. There were no correlations between blood cyanide concentrations
      and causes of death. Volatile analysis suggested postmortem ethanol production
      rather than antemortem ethanol ingestion. No drugs except nicotine were detected
      in any of the victims.

PMID- 1402760
TI  - The elimination rate of mouth alcohol: mathematical modeling and implications in
      breath alcohol analysis.
AB  - Mouth alcohol, if present in high enough concentrations, can falsely bias the
      accurate measurement of end-expiratory breath alcohol. Mouth alcohol will be
      eliminated over time, however, and can be modeled with a single term decaying
      exponential of the form: B0e-kt + C. It is important, however, to determine the
      model and its parameters when alcohol is already present within the biologic
      system. Using three individuals as their own controls, mouth alcohol was
      administered both before and after alcohol consumption followed by breath alcohol
      analysis performed at approximately 0.5 min intervals. The results showed that
      both model parameters (B0 and k) are effected and that the asymptotic value (C)
      is reached much sooner when alcohol already exists in the end-expiratory breath.
      Considering only three individuals were involved, the forensic-science importance
      appears to be that, as the end-expiratory breath alcohol concentration increases,
      the time necessary for the mouth alcohol to decrease to unbiased levels is
      decreased. Fifteen min of observation time prior to breath alcohol analysis
      appears to be more than adequate at forensically relevant concentrations.

PMID- 1402761
TI  - A simple technique for age estimation in adult corpses: the two criteria dental
      method.
AB  - A method for age determination of adults from single rooted teeth is presented.
      It is based on the measurement of two dental features: periodontosis height times
      100/root height (P) and transparency of the root height times 100/root height
      (T). These measurements are made on the labial surface of the entire tooth
      without section and do not require special equipment or training. The application
      of multiple regression analysis to a working sample of 306 teeth of known age,
      sex and race provided the following equation: Age (years) = 0.18 x P + 0.42 x T +
      25.53. The mean error between the actual and estimated age was +/- 10 years on
      the working sample and +/- 8.4 years on a control sample made of 45 forensic
      science cases. Upper incisors showed a better precision than the other single
      rooted teeth and accuracy was not sex related. A comparison of the Gustafson and
      Lamendin methods on a control sample of 39 teeth resulted in an advantage of the
      latter considering the mean error on the estimation (14.2 +/- 3.4 years for
      Gustafson versus 8.9 +/- 2.2 for Lamendin). The Lamendin method can be practical
      interest for any forensic pathologist or dentist as it is fast, easy to use, and
      reasonably accurate except for cases of individuals under age 40 where other
      methods must be preferred.

PMID- 1402762
TI  - Human osteology: key to the sequence of events in a postmortem shooting.
AB  - Forensic anthropologic examination of human skeletal remains found when a field
      was plowed provides evidence of both perimortem trauma, suggesting cause of
      death, and of subsequent shooting of the disarticulated skeleton. The case
      exemplifies the application of the specialized skills and knowledge of the
      physical anthropologist to determination of the postmortem sequence of events.

PMID- 1402763
TI  - Rare electrocution due to powerline contact in a hot-air balloon: comparison with
      fatalities from blunt trauma.
AB  - Powerline contact by hot-air balloons is one of the most frequent concurrences in
      balloon accidents resulting in injury or death. Injuries and deaths are usually a
      result of blunt trauma from falls. In this report, we describe the aircraft, the
      circumstances of the accidents and the autopsy data in two powerline contact
      accidents involving three deaths, one from electrocution and two, from blunt
      trauma sustained in falls. Appropriate pilot behavior is briefly discussed.

PMID- 1402764
TI  - Sudden death due to intravascular hemolysis after bladder irrigation with
      distilled water.
AB  - A 45-year-old white man was hospitalized with gross hematuria, one month after
      cystoscopy and biopsy for the same complaint. The biopsy revealed cystitis
      glandularis. One day after admission, he developed seizures and died within
      hours. Autopsy, laboratory tests, and further questioning of the hospital staff
      showed that he died of acute hyponatremia and massive intravascular hemolysis
      after irrigating the bladder with sterile water. Two deep bladder ulcers with
      exposed veins served as the portals of entry. Until now, this fatal complication
      had been described only during transurethral surgery. Both a careful autopsy and
      hospital investigation is necessary to differentiate in-hospital natural death
      from iatrogenic fatality.

PMID- 1402765
TI  - Fatal virus-associated hemophagocytic syndrome in a young adult producing
      nontraumatic splenic rupture.
AB  - A 24-year-old man with no previous medical history was admitted to a local
      hospital with pancytopenia after a recent "viral illness." During his
      hospitalization, he developed sudden abdominal distension and hypotension.
      Surgical exploration of his abdomen revealed a ruptured spleen. The spleen was
      removed, but the patient did not survive the operation. We investigated this
      unexpected and unexplained hospital death for any traumatic or iatrogenic injury.
      The cause of death after review of the clinical history, autopsy, and microscopic
      sections was virus-associated hemophagocytic syndrome (VAHS). VAHS consists of a
      generalized histiocytic proliferation and marked hemophagocytosis associated with
      a systemic viral infection. Clinically it presents as pancytopenia and
      organomegaly. This recently described entity is often confused with malignant
      histiocytosis. This is the first case report of VAHS producing nontraumatic
      splenic rupture, thus adding to the differential diagnosis of spontaneous splenic
      rupture and sudden natural death.

PMID- 1402766
TI  - Fatal angioedema associated with captopril.
AB  - A markedly hypertensive, 70-year-old, black man had been on captopril for 2 years
      when he rapidly developed obstructive angioedema. The initial sign of difficulty
      in understanding his speech progressed to severe laryngeal and glossal edema over
      a 3 1/2 h period. His airway became obstructed less than a minute after arrival
      at the emergency room. Oral intubation was unsuccessful, and a difficult
      tracheostomy was too late to save the patient. The death was reported to the
      medical examiner because of its sudden and unusual nature. The risk of angioedema
      while on angiotensin converting enzyme inhibitor therapy has been noted
      previously in the clinical literature. Because of the sudden onset and possible
      confusion with an allergic reaction, this entity is brought to the attention of
      the forensic medical community.

PMID- 1402767
TI  - Fatal hydrocarbon lipoid pneumonia and pneumonitis secondary to automatic
      transmission fluid ingestion.

PMID- 1402768
TI  - Spontaneous clostridial myonecrosis.
AB  - Spontaneous, nontraumatic clostridial myonecrosis is a rare infection with an
      insidious onset and usually fatal outcome. Spontaneous clostridial myonecrosis
      has a frequent association with colon carcinoma, leukemia, diabetes mellitus, and
      drug-induced immunosuppression. We present the case of a 73-year-old diabetic man
      who died of spontaneous Clostridium septicum myonecrosis, who had presented with
      fulminant gangrene of the right thigh. Clostridium septicum was cultured from the
      quadriceps muscle postmortem. At autopsy, in addition to the gangrene, there was
      a Duke's A adenocarcinoma of the cecum, which had not been diagnosed during life.
      When spontaneous nontraumatic clostridial myonecrosis is diagnosed at autopsy,
      investigation should include through exam and the obtaining of past medical
      history in order to elucidate predisposing factors.

PMID- 1402769
TI  - Adjusting the focus on America's future health-care plan.

PMID- 1402770
TI  - Aerospace medicine and life sciences at John F. Kennedy Space Center.
      Introduction.

PMID- 1402771
TI  - Space medicine.

PMID- 1402772
TI  - Cardiovascular physiology. Effects of microgravity.
AB  - Experiments during spaceflight and its groundbase analog, bedrest, provide
      consistent data which demonstrate that numerous changes in cardiovascular
      function occur as part of the physiological adaptation process to the
      microgravity environment. These include elevated heart rate and venous
      compliance, lowered blood volume, central venous pressure and stroke volume, and
      attenuated autonomic reflex functions. Although most of these adaptations are not
      functionally apparent during microgravity exposure, they manifest themselves
      during the return to the gravitational challenge of earth's terrestrial
      environment as orthostatic hypotension and instability, a condition which could
      compromise safety, health and productivity. Development and application of
      effective and efficient countermeasures such as saline "loading," intermittent
      venous pooling, pharmacological treatments, and exercise have become primary
      emphases of the space life sciences research effort with only limited success.
      Successful development of countermeasures will require knowledge of the
      physiological mechanisms underlying cardiovascular adaptation to microgravity
      which can be obtained only through controlled, parallel groundbased research to
      complement carefully designed flight experiments. Continued research will provide
      benefits for both space and clinical applications as well as enhance the basic
      understanding of cardiovascular homeostasis in humans.

PMID- 1402773
TI  - Skeletal muscle responses to unloading with special reference to man.
AB  - The limited space flight data suggest that exposure to microgravity decreases
      muscle strength in humans and muscle mass in lower mammals. Several earth-based
      models have been used to address the effect of unloading on the human
      neuromuscular system due to the limited access of biological research to long
      term space flight. Bedrest eliminates body weight bearing of both lower limbs.
      Unilateral lower limb suspension (ULLS), where all ambulatory activity is
      performed on crutches with an elevated sole on the shoe of one foot, has recently
      been used to unload one lower limb. The results from studies using these two
      models support their efficacy. The decrease in strength of m. quadriceps femoris,
      for example, after four to six weeks of bedrest, ULLS or space flight is 20 to
      25%. The results from the earth-based studies show that this response can be
      attributed in part to a decrease in the cross-sectional area of the KE which
      reflects muscle fiber atrophy. The results from the ground based studies also
      support the limited flight data and show that reductions in strength are larger
      in lower than upper limbs and in extensor than flexor muscle groups. They also
      raise issue with the generally held concept that postural muscle is most affected
      by unweighting. Slow-twitch fibers in lower limb muscles of mixed fiber type
      composition and muscle composed mainly of slow-twitch fibers do not
      preferentially atrophy after bedrest or ULLS. Taken together, the data suggest
      that unloading causes remarkable adaptations in the neuromuscular system of
      humans. It should be appreciated, however, that this area of research is in its
      infancy.

PMID- 1402774
TI  - Biomedical engineering. A means to add new dimension to medicine and research.
AB  - Biomedical engineering is an evolving science that seeks to insert technically
      oriented and trained personnel to assist medical professionals in solving
      technological problems in the pursuit of innovations in the delivery of health
      care. Consequently, engineering solutions are brought to bear on problems that
      previously were outside the training of physicians and beyond the understanding
      or appreciation of the conventionally educated electrical or mechanical
      engineers. This physician/scientist/engineer team has a capability to extend
      medicine and research far beyond the capability of a single entity operating
      alone. How biomedical engineering has added a new dimension to medical science at
      the Kennedy Space Center is described.

PMID- 1402775
TI  - Environmental monitoring and research at the John F. Kennedy Space Center.
AB  - The Biomedical Operations and Research Office at the NASA John F. Kennedy Space
      Center has been supporting environmental monitoring and research since the mid
      1970s. Program elements include monitoring of baseline conditions to document
      natural variability in the ecosystem, assessments of operations and construction
      of new facilities, and ecological research focusing on wildlife habitat
      associations. Information management is centered around development of a
      computerized geographic information system that incorporates remote sensing and
      digital image processing technologies along with traditional relational data base
      management capabilities. The proactive program is one in which the initiative is
      to anticipate potential environmental concerns before they occur and, by
      utilizing in-house expertise, develop impact minimization or mitigation
      strategies to reduce environmental risk.

PMID- 1402776
TI  - Kennedy Space Center environmental health program.
AB  - The Kennedy Space Center's environmental health organization is responsible for
      programs which assure its employees a healthful workplace under diverse and
      varied working conditions. These programs encompass the disciplines of industrial
      hygiene, radiation protection (health physics), and environmental
      sanitation/pollution control. Activities range from the routine, such as normal
      office work, to the highly specialized, such as the processing of highly toxic
      and hazardous materials.

PMID- 1402777
TI  - Emergency medical operations at Kennedy Space Center in support of space shuttle.
AB  - The unique environment of the Kennedy Space Center includes a wide variety of
      industrial processes culminating in launch and spaceflight. Many are potentially
      hazardous to the work force and the astronauts. Technology, planning, training,
      and quality control are utilized to prevent contingencies and expedite response
      should a contingency occur.

PMID- 1402778
TI  - Health services at the Kennedy Space Center.
AB  - Comprehensive occupational health services are provided to approximately 17,000
      workers at the Kennedy Space Center and an additional 6000 on Cape Canaveral Air
      Force Station. These areas cover about 120,000 acres encompassing part of the
      Merritt Island Wild Life Refuge and wetlands which are the habitat of numerous
      endangered and protected species of wildlife. The services provided at the
      Kennedy Space Center optimally assure a safe and healthy working environment for
      the employees engaged in the preparation and launching of this country's Space
      Shuttle and other important space exploration programs.

PMID- 1402779
TI  - Healthy start strengthening public and private partnership.

PMID- 1402781
TI  - OSHA redux.

PMID- 1402780
TI  - Role of atrial natriuretic factor in salt and water homeostasis.
AB  - Studies over the past 10 years suggest that the atrial natriuretic factor (ANF)
      plays an important role in salt and water homeostasis. Responding to atrial
      stretch, the atria releases ANF into the circulation. The several actions of this
      hormone tend to increase renal NaCl excretion resulting in reduced blood volume
      and blood pressure. ANF increases the glomerular filtration rate and reduces
      sodium chloride reabsorption in the distal nephron. It also inhibits secretion of
      aldosterone from the adrenal cortex. Therefore actions of ANF appear to be
      opposed to the renin-angiotensin-aldosterone system. Drugs that alter ANF
      metabolism may constitute a new mechanism of treatment for hypertension and heart
      failure.

PMID- 1402782
TI  - Chemical properties of the divalent cation binding site on potassium channels.
AB  - The actions of divalent cations on voltage-gated ion channels suggest that these
      cations bind to specific sites and directly influence gating kinetics. We have
      examined some chemical properties of the external divalent cation binding sites
      on neuronal potassium channels. Patch clamp techniques were used to measure the
      electrophysiological properties of these channels and Zn ions were used to probe
      the divalent cation binding site. The channel activation kinetics were greatly
      (three- to fourfold) slowed by low (2-5 mM) concentrations of Zn; deactivation
      kinetics were only slightly affected. These effects of Zn were inhibited by low
      solution pH in a manner consistent with competition between Zn and H ions for a
      single site. The apparent inhibitory pK for this site was near 7.2. Treatment of
      the neurons with specific amino acid reagents implicated amino, but no histidyl
      or sulfhydryl, residues in divalent cation binding.

PMID- 1402783
TI  - Divalent cation block and competition between divalent and monovalent cations in
      the large-conductance K+ channel from Chara australis.
AB  - The patch-clamp technique is used to investigate divalent ion block of the large
      conductance K+ channel from Chara australis. Block by Ba2+, Ca2+, Mg2+, and
      Pt(NH3)4(2+) from the vacuolar and cytoplasmic sides is used to probe the
      structure of, and ion interactions within, the pore. Five divalent ion binding
      sites are detected. Vacuolar Ca2+ reduces channel conductance by binding to a
      site located 7% along the membrane potential difference (site 1, delta = 0.07;
      from the vacuolar side); it also causes channel closures with mean a duration of
      approximately 0.1-1 ms by binding at a deeper site (site 2, delta = 0.3). Ca2+
      can exit from site 2 into both the vacuolar and cytoplasmic solutions.
      Cytoplasmic Ca2+ reduces conductance by binding at two sites (site 3, delta = 
      0.21; site 4, delta = -0.6; from the cytoplasmic side) and causes closures with a
      mean duration of 10-100 ms by binding to site 5 (delta = -0.7). The deep sites
      exhibit stronger ion specificity than the superficial sites. Cytoplasmic Ca2+
      binds sequentially to sites 3-5 and Ca2+ at site 5 can be locked into the pore by
      a second Ca2+ at site 3 or 4. Ca2+ block is alleviated by increasing [K+] on the
      same side of the channel. Further, Ca2+ occupancy of the deep sites (2, 4, and 5)
      is reduced by K+, Rb+, NH4+, and Na+ on the opposite side of the pore. Their
      relative efficacy correlates with their relative permeability in the channel.
      While some Ca2+ and K+ sites compete for ions, Ca2+ and K+ can simultaneously
      occupy the channel. Ca2+ binding at site 1 only partially blocks channel
      conduction. The results suggest the presence of four K+ binding sites on the
      channel protein. One cytoplasmic facing site has an equilibrium affinity of 10 mM
      (site 6, delta = -0.3) and one vacuolar site (site 7, delta less than 0.2) has
      low affinity (greater than 500 mM). Divalent ion block of the Chara channel shows
      many similarities to that of the maxi-K channel from rat skeletal muscle.

PMID- 1402784
TI  - The human erythrocyte anion transport protein, band 3. Characterization of
      exofacial alkaline titratable groups involved in anion binding/translocation.
AB  - Chloride self-exchange across the human erythrocyte membrane at alkaline
      extracellular pH (pHO) and constant neutral intracellular pH (pH(i)) can be
      described by an exofacial deprotonatable reciprocating anion binding site model.
      The conversion of the transport system from the neutral to the alkaline state is
      related to deprotonation of a positively charged ionic strength- and substrate
      sensitive group. In the absence of substrate ions ([ClO] = 0) the group has a pK
      of approximately 9.4 at constant high ionic strength (equivalent to approximately
      150 mM KCl) and a pK of approximately 8.7 at approximately zero ionic strength.
      The alkaline ping-pong system (examined at constant high ionic strength)
      demonstrates outward recruitment of the binding sites with an asymmetry factor of
      approximately 0.2, as compared with the inward recruitment of the transport
      system at neutral pHO with an asymmetry factor of approximately 10. The intrinsic
      half-saturation constant for chloride binding, with [Cli] = [Clo], increased from
      approximately 30 mM at neutral to approximately 110 mM at alkaline pHO. The
      maximal transport rate was a factor of approximately 1.7 higher at alkaline pHO.
      This increase explains the stimulation of anion transport, the "modifier hump,"
      observed at alkaline pHO. The translocation of anions at alkaline pHO was
      inhibited by deprotonation of another substrate-sensitive group with an intrinsic
      pK of approximately 11.3. This group together with the group with a pK of
      approximately 9.4 appear to form the essential part of the exofacial anion
      binding site. The effect of extracellular iodide inhibition on chloride transport
      as a function of pHO could, moreover, be simulated if three extracellular iodide
      binding constants were included in the model: namely, a competitive intrinsic
      iodide binding constant of approximately 1 mM in the neutral state, a self
      inhibitor binding constant of approximately 120 mM in the neutral state, and a
      competitive intrinsic binding constant of approximately 38 mM in the alkaline
      state.

PMID- 1402785
TI  - Lactic acid secretion by human neutrophils. Evidence for an H+ + lactate-
      cotransport system.
AB  - The pathway by which L-lactate (Lac) crosses the plasma membrane of isolated
      human neutrophils was investigated. The influx of [14C]Lac from a 2 mM Lac, 145
      mM Cl-, 5.6 mM glucose medium was approximately 1.5 meq/liter of cell water.min
      and was sensitive to the organomercurial agent mersalyl (apparent Ki
      approximately 20 microM), to alpha-cyano-4-hydroxycinnamate (CHC), the classical
      inhibitor of monocarboxylate transport in mitochondria, and to UK-5099 (apparent
      Ki approximately 40 microM), a more potent analogue of CHC. Transport was also
      strongly blocked (greater than 80%) by 1 mM of either 3,5-diiodosalicylic acid,
      MK-473 (an indanyloxyacetate derivative), or diphenyl-amine-2-carboxylate, and by
      0.4 mM pentachlorophenol, but not by 1 mM ethacrynic acid, furosemide, or the
      disulfonic stilbenes SITS or H2DIDS. One-way [14C]Lac efflux from steady-state
      cells amounted to approximately 6 meq/liter.min and was likewise affected by the
      agents listed above. Influx, which was membrane potential insensitive and Na+
      independent, displayed a strong pH dependence: extracellular acidification
      enhanced uptake while alkalinization inhibited the process (pK' approximately 5.7
      at 2 mM external Lac). The rate of [14C]Lac influx was a saturable function of
      external Lac, the Km being approximately 7 mM. Steady-state cells exhibited an
      intracellular Lac content of approximately 5 mM and secreted lactic acid into the
      bathing medium a a rate of approximately 4 meq/liter.min. Secretion was
      completely suppressed by 1 mM mersalyl which inactivates the carrier, leading to
      an internal accumulation of Lac. That the Lac carrier truly mediates an H+ + Lac-
      cotransport (or formally equivalent Lac-/OH- exchange) was documented by pH-stat
      techniques wherein an alkalinization of poorly buffered medium could be detected
      upon the addition of Lac; these pH changes were sensitive to mersalyl. Thus, the
      Lac carrier of neutrophils possesses several features in common with other
      monocarboxylate transport systems in erythrocytes and epithelia.

PMID- 1402786
TI  - Catabolism in mollicutes.
AB  - The small genome size of mollicutes, and particularly mycoplasmas and
      ureaplasmas, precludes their possession of the extensive range of metabolic
      activities present in most other bacterial groups. Demonstrated catabolic
      activities appear primarily to be associated with energy generation, rather than
      the provision of substrates for synthetic pathways, and anabolism is largely
      dependent upon extracellular sources of amino acids, nucleic acid precursors and
      lipids. However, the pathways of energy generation in mollicutes are diverse and
      specialized, and may in vivo be dependent upon the presence of a single amino
      acid (arginine) or urea. Even in those species that utilize carbohydrates the
      range of substrates is restricted, and while Ac. laidlawii has both EMP and PP
      pathways and is able to oxidize pyruvate to acetate plus CO2, many mycoplasmas
      possess only a part of these activities. Such specialization and the infrequent
      demonstration of inducible enzyme activity in mollicutes implies adaptation to
      specific habitats in host species, and suggests that differences in the catabolic
      activities of mollicute strains may be significant in terms of their ecology and
      pathogenicity. The demonstrated energy-generating pathways of mollicutes produce
      low ATP yields. Thus, mollicute growth will generate relatively large quantities
      of metabolic end-products and may deplete host tissues of substrates. Arginine
      depletion may be of particular importance in pathogenesis and the close physical
      association between mollicutes and host cells will enhance the potential
      significance of NH4+ production from the hydrolysis of arginine and urea, and of
      H2O2 and superoxide formation during carbohydrate metabolism. In addition, lipid
      and protein catabolism may be associated with virulence where extracellular or
      membrane-bound enzyme activities exist. Membrane-bound DNAase and RNAase
      activities have also been demonstrated in mycoplasmas and Ac. laidlawii (Pollack
      et al., 1965) and U. urealyticum (Romano & La Licata, 1978). Many aspects of
      mollicute catabolism, including energy conservation in some groups, is poorly
      understood. Also, while substantial catabolic diversity has been demonstrated
      within mollicutes and new species are continually being isolated, metabolism has
      been studied in relatively few species, and even in these only single strains or
      small groups of strains have been used. In this review, therefore, an attempt to
      avoid generalizations concerning mollicute behaviour has been made. The lack of
      much basic knowledge concerning mollicute metabolism has also necessitated the
      widespread use of 'may be' and other equally vague terms.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 1402787
TI  - Cell-bound peptidase activities of Treponema denticola ATCC 33520 in continuous
      culture.
AB  - The oral spirochaete Treponema denticola ATCC 33520 was grown at a mean
      generation time of 10 h in anaerobic continuous culture in a serum- and
      carbohydrate-free medium at pH 7.0. The extracellular proteolytic activities of
      this spirochaete were then investigated by incubating washed cells with 68 2
      naphthylamide derivatives of the Extended API System. Chymotrypsin-like, trypsin
      like, elastase-like and iminopeptidase activities were demonstrated. The
      phenylalanine peptidase or chymotrypsin-like activity of T. denticola ATCC 33520,
      estimated with N-succinyl-L-phenylalanyl-L-leucyl-L-phenylalanine-thiobenzyl
      ester (SPLP) had a pH optimum at pH 8.5, a specific activity of 36.6 nmol min-1
      (mg dry wt)-1 and was inhibited only slightly by HgCl2. The trypsin-like
      activity, estimated with benzoyl-DL-arginine-7-amido-4-methylcoumarin (BAMC), had
      a pH optimum at pH9, and a specific activity of 0.3 nmol min-1 (mg dry wt)-1;
      inhibition by HgCl2 indicated the involvement of active thiol groups. The
      activity should preferably be termed arginine peptidase activity, according to
      the carboxy-terminal amino acid of the test substrate. The extracellular proline
      peptidase activity, estimated with L-proline-7-amido-4-methylcoumarin. HBr
      (PRAMC), had an activity of 1.5 nmol min-1 (mg dry wt)-1, an optimum at pH 8.5
      and the properties of a thiol protease. The main cell-bound and extracellular
      active peptidase activities of fast-growing cells of T. denticola ATCC 33520 are
      phenylalanine peptidase, proline peptidase, arginine peptidase and an
      oligopeptide-dependent alanine peptidase activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402788
TI  - Cloning and physical mapping of the Staphylococcus aureus rplL, rpoB and rpoC
      genes, encoding ribosomal protein L7/L12 and RNA polymerase subunits beta and
      beta'.
AB  - Using segments of the Escherichia coli rpoB and rpoC genes as heterologous
      probes, we have identified and cloned an 8.3 kb PstI fragment from the
      Staphylococcus aureus genome containing the rpoB and rpoC genes, which
      respectively encode the beta and beta' subunits of DNA-directed RNA polymerase.
      This region is almost certainly equivalent to the rif locus, located near to fus
      at interval 12/13 on the S. aureus linkage map. Limited DNA sequencing revealed
      the gene order rpoB-rpoC (transcribed from left to right) and identified the rplL
      gene, encoding ribosomal protein L7/L12, upstream of rpoB. This and other
      evidence suggests that the rpoBC genes of S. aureus form part of a large gene
      cluster encoding components of the transcription and translation apparatus which
      is well-conserved in other eubacteria.

PMID- 1402789
TI  - Micromonospora RNA polymerase activity changes during stationary phase.
AB  - RNA polymerase was isolated from Micromonospora echinospora and from Streptomyces
      lividans. In vitro transcription of a DNA fragment containing multiple tandem
      promoters from Micromonospora followed the pattern of expression observed
      previously for in vivo studies. RNA polymerase was prepared from cultures of
      Micromonospora that were harvested during the growing phase and during the
      stationary phase. Promoters that were utilized in Micromonospora only during the
      stationary phase were utilized in vitro only when RNA polymerase was purified
      from a stationary-phase culture, and not when RNA polymerase was purified from
      growing cells.

PMID- 1402790
TI  - Isolation and characterization of a repeated sequence (RPS1) of Candida albicans.
AB  - A repeated sequence, named RPS1, approximately 2 kb in size, is found mainly in
      chromosome 6, the second most variable chromosome among the eight chromosomes of
      Candida albicans. Most of the RPS1 units of chromosome 6 seem to be located
      within a single region of about 100 kb in strain FC18. In both strains FC18 and
      NUM812, a part of RPS1 is apparently tandemly repeated. A unit of RPS1 has been
      cloned and sequenced. It consists of 2114 bp and has a GC content of 40 mol%. The
      repeat unit contains smaller repeats of about 80-170 bp which are called REP1,
      REP2, REP3, REP4 and REP5; REP2 is duplicated. The small repeats are classified
      into two groups by their homology. One comprises REP1, REP2 and REP5, and the
      other REP3 and REP4. They are termed the REP1 and REP3 families, respectively.
      The two families both contain a common 29 bp sequence, called COM29. The
      dispersed repetitive sequence RPS1 may be involved in chromosomal rearrangements
      and may in part explain chromosome polymorphism in C. albicans. The origin of
      RPS1 was not determined.

PMID- 1402791
TI  - Reduced azole susceptibility of oral isolates of Candida albicans from HIV
      positive patients and a derivative exhibiting colony morphology variation.
AB  - Approximately 50% (15/28) of a selection of oral isolates of Candida albicans
      from separate individuals infected with the human immunodeficiency virus (HIV)
      exhibited low susceptibility to ketoconazole as determined by hyphal elongation
      assessment. Nine of these isolates exhibited colony morphology variation or
      switching at 37 degrees C, of which six expressed low ketoconazole
      susceptibility. To determine whether colony morphology variation could give rise
      to derivatives with reduced azole susceptibility, several high-frequency
      switching variants of three HIV-patient isolates were recovered and assessed. All
      but one of the variants expressed similar azole susceptibility profiles to their
      respective parental strains. However, the C. albicans derivative 132ACR expressed
      significantly reduced susceptibility to ketoconazole in comparison to its
      parental strain 132A. In whole cells, on the basis of total growth the switched
      derivative 132ACR was markedly less susceptible than its parental isolate 132A to
      ketoconazole at 10 microM. A much smaller difference was observed with
      fluconazole at 10 microM, with the switched derivative 132ACR exhibiting a
      threefold lower susceptibility compared with the parental isolate 132A. The
      incorporation of [14C]acetate in control and azole-treated cells of both
      organisms was higher for the parental strain. When cell lysates of strain 132A
      and its derivative 132ACR were incubated with [14C]mevalonic acid and
      ketoconazole, the IC50 for 14C-label incorporation into C-4 demethyl sterols was
      fivefold higher for lysates of the switched derivative 132ACR compared with those
      of the parental strain 132A. With fluconazole the IC50 value for the derivative
      132ACR was 25-fold higher than for strain 132A. The 14-sterol demethylase of the
      switched derivative 132ACR was possibly less sensitive to azole inhibition than
      that of the enzyme of strain 132A. These studies indicated that colony morphology
      variation in vitro can generate derivatives with stable, reduced azole
      susceptibility without prior exposure to azoles.

PMID- 1402792
TI  - Biological activities and chemical composition of a cytotoxin of Klebsiella
      oxytoca.
AB  - A low-molecular-mass cytotoxin produced by Klebsiella oxytoca isolated previously
      from patients with antibiotic-associated haemorrhagic enterocolitis was purified,
      and its biological and chemical properties were elucidated. The toxin inhibited
      the syntheses of DNA and RNA by HEp-2 cells dose-dependently, whereas protein
      synthesis was only slightly inhibited, as measured by the incorporation of
      radioactive precursors. When synchronously cultured HEp-2 cells were examined in
      the presence of cytotoxin, inhibition of DNA synthesis occurred promptly within 5
      h, but cell-rounding, the earliest visible morphological change, was not observed
      until 6 h after exposure. The intracellular levels of ATP decreased with an
      approximately similar time course. These results suggest that cytotoxicity toward
      HEp-2 cells is primarily due to the inhibitory effect of the cytotoxin on nucleic
      acid synthesis, possibly on DNA synthesis. Cell rounding and cell death were
      induced even in the absence of the cytotoxin after incubation with the cytotoxin
      for 6 h. The cytotoxin was heat-labile, cytotoxic activity decreasing to 50% of
      the initial level on heating at 70 degrees C for 20 min. Plasmids were extracted
      from three strains of K. oxytoca producing the cytotoxin and analysed by agarose
      gel electrophoresis. Two strains possessed plasmids of different sizes, but one
      strain possessed no plasmid, indicating that the cytotoxin is probably
      chromosomally encoded. Analysis by NMR and FAB-mass-spectrometry revealed that
      the molecular mass of the cytotoxin should be 217.1062 Da (exact mass), its
      molecular formula being C8H15O4N3.

PMID- 1402793
TI  - The effect of AMP on the NAD-dependent glutamate dehydrogenase during activation
      and morphogenesis in the cellular slime moulds.
AB  - In extracts from vegetative Dictyostelium discoideum V12 the basal NAD-dependent
      glutamate dehydrogenase (NAD-GDH) activity was low, but it increased on standing
      at 4 degrees C. When 0.1 mM-AMP was included in the assay mix, enzyme activity
      was stimulated nearly 30-fold. As the extract was allowed to age, the enzyme
      rapidly lost its ability to be stimulated by AMP. The response of NAD-GDH to AMP
      was also dependent on the stage of morphogenesis. The ratios of NAD-GDH activity
      assayed with and without AMP (+AMP/-AMP ratios) in freshly prepared extracts from
      cells at 0, 4, 8 and 12 h of development were similar, but declined later in
      morphogenesis. The +AMP/-AMP ratio decreased sharply during activation at 4
      degrees C in extracts from cells at 0, 4, 16 and 20 h of development. By
      contrast, extracts from cells starved for 8 and 12 h remained more responsive to
      AMP throughout activation. Analysis of Western blots showed that vegetative NAD
      GDH did not undergo any detectable proteolytic cleavage during 96 h of activation
      at 4 degrees C. Also, no change in molecular mass appeared to take place within
      the cells until culmination (20-24 h), when some breakdown products appeared.
      Activation of NAD-GDH also occurred in D. discoideum strains NC4 and AX3, and in
      D. mucoroides. In addition, the enzyme from these four strains was stimulated by
      AMP and the +AMP/-AMP ratio declined with similar kinetics during activation. The
      enzyme from Polysphondylium violaceum was not activated on standing, but it was
      stimulated by AMP. The effect of activation of NAD-GDH is discussed in relation
      to a postulated catabolic role for this enzyme.

PMID- 1402794
TI  - Long-chain alcohol and aldehyde dehydrogenase activities in Acinetobacter
      calcoaceticus strain HO1-N.
AB  - Three alcohol dehydrogenases have been identified in Acinetobacter calcoaceticus
      sp. strain HO1-N: an NAD(+)-dependent enzyme and two NADP(+)-dependent enzymes.
      One of the NADP(+)-dependent alcohol dehydrogenases was partially purified and
      was specific for long-chain substrates. With tetradecanol as substrate an
      apparent Km value of 5.2 microM was calculated. This enzyme has a pI of 4.5 and a
      molecular mass of 144 kDa. All three alcohol dehydrogenases were constitutively
      expressed. Three aldehyde dehydrogenases were also identified: an NAD(+)
      dependent enzyme, an NADP(+)-dependent enzyme and one which was nucleotide
      independent. The NAD(+)-dependent enzyme represented only 2% of the total
      activity and was not studied further. The NADP(+)-dependent enzyme was strongly
      induced by growth of cells on alkanes and was associated with hydrocarbon
      vesicles. With tetradecanal as substrate an apparent Km value of 0.2 microM was
      calculated. The nucleotide-independent aldehyde dehydrogenase could use either
      Wurster's Blue or phenazine methosulphate (PMS) as an artificial electron
      acceptor. This enzyme represents approximately 80% of the total long-chain
      aldehyde oxidizing activity within the cell when the enzymes were induced by
      growing the cells on hexadecane. It is particulate but can be solubilized using
      Triton X-100. The enzyme has an apparent Km of 0.36 mM for decanal.

PMID- 1402795
TI  - Purification and amino acid sequence of a bacteriocin produced by Pediococcus
      acidilactici.
AB  - A bacteriocin produced by Pediococcus acidilactici has been purified to
      homogeneity by a rapid and simple four-step purification procedure which includes
      ammonium sulphate precipitation, chromatography with a cation-exchanger and Octyl
      Sepharose, and reverse-phase chromatography. The purification resulted in an
      approximately 80,000-fold increase in the specific activity and about a 6-fold
      increase in the total activity. The amino acid composition and sequencing data
      indicated that the bacteriocin contained 43-44 amino acid residues. The predicted
      M(r) and isolectric point of the bacteriocin are about 4600 and 8.6,
      respectively. Comparing the amino acid sequence of this bacteriocin with the
      sequences of leucocin A-UAL 187, sakacin P and curvacin A (bacteriocins produced
      by Leuconostoc gelidum, Lactobacillus sake and Lactobacillus curvatus,
      respectively) revealed that all four bacteriocins had in their N-terminal region
      the sequence Tyr-Gly-Asn-Gly-Val-Xaa-Cys, indicating that this concensus sequence
      is of fundamental importance for this group of bacteriocins. The bacteriocin from
      P. acidilactici and sakacin P were very similar, having at least 25 common amino
      acid residues. The sequence similarity was greatest in the N-terminal half of the
      molecules--17 of the first 19 residues were common--indicating the fundamental
      importance of this region. Leucocin A-UAL 187 and curvacin A had, respectively,
      at least 16 and 13 amino acid residues in common with the bacteriocin from P.
      acidilactici.

PMID- 1402796
TI  - Some highlights of virus research in 1991.

PMID- 1402797
TI  - Defective interfering L RNA segments of tomato spotted wilt virus retain both
      virus genome termini and have extensive internal deletions.
AB  - Defective interfering (DI) RNA molecules derived from the genomic L RNA segment
      of tomato spotted wilt virus (TSWV) were generated during sequential passage of
      the virus at high multiplicity. Characterization of DI RNAs from four distinct
      isolates by Northern blot analysis and sequence determination revealed that both
      the 5' and 3' genomic termini were retained in these molecules. Each DI RNA
      contained a single internal deletion of approximately 60% to 80% of the L RNA
      segment. All DI RNAs studied maintain an open reading frame (ORF) which suggests
      that these defective molecules should be translatable by ribosomes. Detection of
      only defective molecules with ORFs indicates either that association with
      ribosomes or translation is a prerequisite for the selection and maintenance of
      replicating DI RNAs, or that the truncated proteins produced play a role in their
      selection or replication. Analysis of the junction sites in the DI RNAs showed
      that short nucleotide sequences are repeated, one at the release and another at
      the reinitiation point on the L RNA. One of these is lost during the generation
      of the DI molecules. The presence of repeated sequences at the junction sites
      seems to be unique for tospovirus DI L RNAs; they have not been described for
      other DI systems of either positive- or negative-strand RNA viruses. A model for
      TSWV DI RNA generation is proposed in which the viral polymerase can 'jump'
      across the internal sequences from one secondary structure to another containing
      the repeated sequences, during the replication of the viral complementary L RNA
      segment.

PMID- 1402798
TI  - Cross-reacting and heterospecific monoclonal antibodies produced against arabis
      mosaic nepovirus.
AB  - Monoclonal antibodies (MAbs) were produced against arabis mosaic nepovirus (AMV).
      A hybridoma screening procedure was applied which involved the testing of culture
      supernatants, before the hybridomas were cloned to single cell lines, for their
      reaction with eight nepoviruses [AMV, cherry leafroll virus (CLRV), grapevine
      fanleaf virus (GFLV), peach rosette mosaic virus, raspberry ringspot virus
      (RRSV), tobacco ringspot virus, tomato black ring virus (TBRV) and tomato
      ringspot virus]. In addition to AMV-specific MAbs, this screening technique has
      allowed the selection of two cross-reacting MAbs: one reacting with AMV and GFLV,
      and one reacting with AMV and RRSV. This is the first report of MAbs cross
      reacting with these nepoviruses. In addition, five heterospecific MAbs (HS-MAbs)
      could be selected: two reacting with RRSV, two with CLRV and one with TBRV. The
      usefulness of the screening technique that was applied for the selection of cross
      reacting MAbs and HS-MAbs, and the potential use of such antibodies are
      discussed.

PMID- 1402800
TI  - Nucleotide sequence responsible for the synthesis of a truncated coat protein of
      brome mosaic virus strain ATCC66.
AB  - The ATCC66 strain of brome mosaic virus (BMV) (propagated at Kyoto University)
      contained two types of coat protein in its virion whereas the Russian strain of
      BMV has been known to contain a single coat protein; both strains have two
      initiation codons for coat protein in the same reading frame at the 5'-proximal
      end of the gene in RNA 4. Comparative studies on the nucleotide sequences of the
      ATCC66 and Russian strains of BMV demonstrated that in the ATCC66 strain, two
      adjacent adenine residues were absent from RNA 3 in the leader sequences of the
      coat protein gene just a few nucleotides 5' to the first initiation codon of the
      coat protein gene. Using biologically active cDNA clones of BMV RNA of the ATCC66
      strain, we inserted two adjacent adenine residues into the cDNA of RNA 3 to
      obtain an RNA 3 transcript which has the same nucleotide sequence as the Russian
      strain in the non-coding leader sequence of the coat protein gene. Barley
      protoplasts inoculated with this RNA 3 transcript together with RNA 1 and 2
      produced a single coat protein. To obtain further insight into the mechanism of
      translation of the BMV coat protein, we constructed several types of RNA 4 by
      changing the sequence surrounding the first AUG codon in the coat protein gene
      and analysed the in vitro translation products of the mutant RNA 4. The results
      confirmed that the absence of the two adjacent adenine residues was responsible
      for the production of two types of coat protein in the ATCC66 strain. The
      deletion of the two adjacent adenine residues in ATCC66 resulted in a base
      substitution of A with U three nucleotides 5' to the first AUG in the coat
      protein gene. The base substitution reduced translational activity from the first
      AUG codon and concomitantly increased translational activity from the second AUG
      codon from which a truncated coat protein was translated.

PMID- 1402799
TI  - Complete nucleotide sequence and genetic organization of papaya ringspot virus
      RNA.
AB  - The complete nucleotide sequence of the RNA genome of papaya ringspot virus
      (PRSV) was determined from four overlapping cDNA clones and by direct sequencing
      of viral RNA. The genomic RNA is 10326 nucleotides in length, excluding the
      poly(A) tract, and contains one large open reading frame that starts at
      nucleotide positions 86 to 88 and ends at positions 10118 to 10120, encoding a
      polyprotein of 3344 amino acids. The highly conserved sequence
      AAAUAAAANANCUCAACACAACAUA at the 5' end of the RNA of PRSV and those of the other
      five reported potyviruses shows 80% similarity, suggesting that this region may
      play a common important role for potyvirus replication. Two cleavage sites of the
      polyprotein were determined by amino acid sequencing of the N termini of helper
      component (HC-Pro, amorphous inclusion) and cylindrical inclusion (CI) proteins.
      Other cleavage sites were predicted by analogy with the other potyviruses. The
      genetic organization of PRSV is similar to that of the other potyviruses except
      that the first protein processed from the N terminus of the polyprotein (NT
      protein) has an M(r) of 63K, 18K to 34K larger than those of the other
      potyviruses. The cleavage site for liberating the N terminus of the HC-Pro
      protein was found at the same location down-stream from the consensus sequence
      FI(V)VRG as that reported for tobacco vein mottling virus. The NT protein of
      potyviruses is the most variable and may be considered important for
      identification of individual potyviruses. The most conserved protein of
      potyviruses appears to be the NIb protein, the putative polymerase for the
      replication of the potyviral RNA. The genetic organization of PRSV RNA is
      tentatively proposed to be VPg-5' leader-63K NT-52K HC-Pro-46K-72K CI-6K-48K NIa
      59K NIb-35K coat protein-3' non-coding region-poly(A) tract.

PMID- 1402801
TI  - Stimulation of specific immune responses to simian immunodeficiency virus using
      chimeric hepatitis B core antigen particles.
AB  - Subunit approaches to vaccines against viral diseases have resulted in the
      development of a number of methods for presentation of defined epitopes to the
      immune system. We have exploited a highly immunogenic presentation system based
      on hepatitis B core antigen (HBcAg) particles to produce a number of candidate
      vaccines against simian immunodeficiency virus (SIV). Recombinant particles have
      been produced in bacteria which carry multiple copies of defined or predicted
      neutralizing epitopes of SIV at a number of different sites within the particle.
      In parallel, a number of synthetic peptide-based SIV vaccines have been produced
      based on homology to reported neutralizing epitopes in human immunodeficiency
      virus. Although potent immune responses were elicited against both particulate
      and peptide forms of the antigen, neutralizing antibodies were not induced as
      judged by available assays.

PMID- 1402802
TI  - Synthesis and processing of the haemagglutinin-esterase glycoprotein of bovine
      coronavirus encoded in the E3 region of adenovirus.
AB  - The haemagglutinin-esterase gene (HE) of bovine coronavirus (BCV) encodes a major
      viral membrane glycoprotein that elicits BCV-neutralizing antibodies. The BCV HE
      gene was cloned into a human adenovirus serotype 5 (Ad5) transfer vector in place
      of early transcription region 3, and a helper-independent recombinant virus was
      constructed by rescue of the transcription unit by homologous in vivo
      recombination between the vector and Ad5 genomic DNA. The BCV HE polypeptide
      expressed by this recombinant Ad was characterized in vivo and in vitro. A 65K
      polypeptide was identified using an anti-BCV antibody in both human (293) and
      bovine (MDBK) cells infected with the recombinant Ad. In the absence of a
      reducing agent, migration of the 65K polypeptide was shifted to 130K, indicating
      that the recombinant HE polypeptide existed in a dimeric form. The HE polypeptide
      was glycosylated, as demonstrated by labelling with [3H]glucosamine, and was
      immunoreactive with three distinct groups of conformation-specific anti-HE
      monoclonal antibodies (MAbs). Cells infected with recombinant Ad expressing BCV
      HE exhibited both haemadsorption activity and acetylesterase activity. In
      addition, the anti-HE group A MAbs HC10-5 and KD9-40 inhibited both the
      haemadsorption activity and esterase activity of the recombinant HE polypeptide,
      suggesting that the antigenic domain responsible for BCV neutralization may
      overlap (or is closely associated with) the domain(s) responsible for
      haemagglutination and/or acetylesterase activities. When mice were inoculated
      intraperitoneally with live recombinant Ad, a significant level of BCV
      neutralizing HE-specific antibody was induced. These results indicate that the
      recombinant Ad replicates and directs the synthesis of the BCV HE polypeptide in
      vivo.

PMID- 1402804
TI  - A monoclonal antibody recognizes a human cell surface glycoprotein involved in
      measles virus binding.
AB  - Measles virus (MV) has a very limited host range, humans being the only natural
      reservoir of the virus. This restriction may be due to the absence of an MV
      receptor on the surface of non-primate cells. We have studied the MV-binding
      ability of several cell lines and attempted to characterize the receptor by
      studying the binding of 35S-labelled MV and by a rosette formation technique. We
      confirmed that all the human cell lines examined (HeLa, Raji and Jurkat) bound MV
      and that the murine cell lines (BW and L) did not. The glycoprotein nature of the
      receptor activity was demonstrated by the fact that it could be removed from the
      cell membrane using proteolytic enzymes and by its failure to be re-expressed in
      the presence of a protein synthesis inhibitor or an N-glycosylation inhibitor. A
      monoclonal antibody isolated after immunization of mice with Raji cells
      specifically inhibited MV binding and infection of human cells, and recognized
      human and simian but not murine cells. Depending on the cell line (HeLa, Raji,
      Jurkat or Vero), this antibody immunoprecipitated one or two glycoproteins with
      apparent M(r)s of 57K and/or 67K from human and simian cells, but not from murine
      cells.

PMID- 1402803
TI  - Nucleotide sequence of the tick-borne orthomyxo-like Dhori/India/1313/61 virus
      membrane protein gene.
AB  - The complete nucleotide sequence of the sixth largest segment of ssRNA (RNA-6) of
      the tick-borne orthomyxo-like Dhori/India/1313/61 virus was determined by using
      cloned cDNA derived from infected cell mRNA and dideoxynucleotide sequencing of
      viral RNA. RNA-6 contains 962 nucleotides and is predicted to encode a protein of
      270 amino acids with an M(r) of 30,498 in its first open reading frame (ORF).
      This protein is likely to represent the viral membrane (M1) protein, based on its
      predicted M(r) of 29,000 (estimated by PAGE), its relatively high abundance in
      infected cells and amino acid composition analysis. In addition, a second ORF was
      found which overlaps the M1 protein gene sequence by 327 nucleotides. This
      additional reading frame, in the +3 frame, potentially can encode a protein of
      141 amino acids. However, S1 nuclease analysis of RNA-6 mRNA from infected cells
      indicated that there was only a single abundant RNA species corresponding in size
      to the full-length genomic RNA (0.96 kb). Further studies are needed to determine
      whether expression of the second ORF occurs and how that expression might arise.

PMID- 1402805
TI  - Differential effect of DNA supercoiling on transcription of adenovirus genes in
      vitro.
AB  - We examined the effect of DNA template topology on the transcription of immediate
      early (E1a), early (E1b) and late (pIX) adenovirus genes in vitro. Transcription
      in whole cell extracts was measured by quantitative hybridization to end-labelled
      DNA and protection of hybrids from S1 nuclease digestion. Two- to fourfold more
      E1a RNA was synthesized from supercoiled, compared to linear, DNA templates.
      Similarly, transcription of the E1b gene was stimulated three- to sevenfold when
      the template was supercoiled. In contrast, RNA synthesis from the late pIX gene
      was found to be independent of DNA topology. These results show that DNA topology
      affects transcription in a promoter-specific manner.

PMID- 1402806
TI  - Sequence analysis of the membrane protein gene of human coronavirus OC43 and
      evidence for O-glycosylation.
AB  - The gene encoding the membrane (M) protein of the OC43 strain of human
      coronavirus (HCV-OC43) was amplified by a reverse transcription-polymerase chain
      reaction of viral RNA with HCV-OC43- and bovine coronavirus (BCV)-specific
      primers. The nucleotide sequence of the cloned 1.5 kb fragment revealed an open
      reading frame (ORF) of 690 nucleotides which was identified as the M protein gene
      from its homology to BCV. This ORF encodes a protein of 230 amino acids with an
      M(r) of 26416. The gene is preceded by the motif UCCAAAC, analogous to the
      consensus coronavirus transcription initiation sequence. The M protein of HCV
      OC43 shows features typical of all coronavirus M proteins studied: a hydrophilic,
      presumably external N terminus including about 10% of the protein, and a
      potential N-glycosylation site followed by three major hydrophobic transmembrane
      domains. The amino acid sequence of the M protein of HCV-OC43 has 94% identity
      with that of the Mebus strain of BCV, and also contains six potential O
      glycosylation sites in the exposed N-terminal domain. Indeed, the glycosylation
      of the M protein was not inhibited in the presence of tunicamycin, which is
      indicative of O-glycosylation, as previously reported for BCV and murine
      hepatitis virus. Virions released from tunicamycin-treated cells contained the M
      glycoprotein but were devoid of both peplomer (S) and haemagglutinin-esterase
      (HE) proteins. Thus, inhibition of the N-glycosylation of the S and HE structural
      proteins prevented their incorporation into progeny virions, an indication that
      they are dispensable for virion morphogenesis, unlike the M protein.

PMID- 1402807
TI  - Antigenic and genetic characterization of the haemagglutinins of recent
      cocirculating strains of influenza B virus.
AB  - The antigenic and genetic characteristics of the haemagglutinins of influenza
      type B viruses isolated since 1988 during periods of both widespread activity
      (1990/1991) and sporadic activity (1989/1990) were examined using
      microneutralization tests and direct RNA sequencing. During 1989/1990, influenza
      B viruses representative of two distinct lineages antigenically and genetically
      related to either B/Victoria/2/87 or B/Yamagata/16/88 were isolated, and a minor
      drift variant of B/Yamagata/16/88, B/Hong Kong/22/89, was identified. In
      1990/1991, B/Hong Kong/22/89- or B/Yamagata/16/88-like viruses accounted for the
      majority of the influenza virus isolates in most countries. Sequence analysis of
      the HA1 domains of representative viruses confirmed the continued existence of
      two main lineages among recent strains of influenza B virus and identified unique
      amino acid changes that could account for the altered antigenic reactivity of
      some variants. Sequence analysis of the HA2 domains of some of the recent
      influenza B viruses allowed for a comparison of the evolutionary rates and
      patterns between the HA1 and HA2 domains.

PMID- 1402808
TI  - Geminivirus replication proteins are related to prokaryotic plasmid rolling
      circle DNA replication initiator proteins.
AB  - It is demonstrated, by means of computer-assisted analysis, that C1 protein
      involved in the replication of geminivirus DNA is related to the rolling circle
      replication initiator proteins of eubacterial plasmids, particularly the plasmids
      of the pMV158 family. Three sequence motifs conserved in the geminivirus and
      plasmid replication proteins were delineated, one of them encompassing the Tyr
      residue that presumably forms a covalent linkage to DNA. These findings are
      compatible with the results of recent analyses of geminivirus replicative
      intermediates suggesting a rolling circle mechanism for geminivirus DNA
      replication. It is hypothesized that C1 protein initiates the rolling circle
      replication of geminivirus DNA by nicking a specific site in the virus-sense DNA
      and covalently linking to the 5' side of the nick. The putative rolling circle
      replication initiator domain comprises the N-terminal portion of C1, whereas its
      C-terminal part is a putative helicase domain. By analogy with prokaryotic
      systems, it is speculated that the replication initiator domain and the helicase
      domain function coordinately. The possibility of the origin of geminiviruses from
      prokaryotic circular ssDNA replicons is discussed.

PMID- 1402810
TI  - A zucchini yellow mosaic virus coat protein gene mutation restores aphid
      transmissibility but has no effect on multiplication.
AB  - An aphid-transmissible (AT) and two non-aphid-transmissible (NAT) isolates of
      zucchini yellow mosaic virus (ZYMV) were studied. The predicted amino acid
      sequences of the coat protein (CP) of the three virus isolates were analysed and
      compared. The NAT isolates differed from the AT isolate in having a Thr instead
      of an Ala residue at position 10 in the conserved Asp-Ala-Gly triplet in the N
      terminal region of CP. Aphid transmissibility was restored in a progeny virus
      derived from an infectious clone of the ZYMV-NAT isolate in which Thr was changed
      back to Ala by site-directed mutagenesis. However this mutation did not have any
      effect on the multiplication rate in squash, which was significantly higher than
      that of the AT isolate. The involvement of this mutation in aphid transmission
      and virus multiplication is discussed.

PMID- 1402809
TI  - Sequence analysis of the 3'-terminal halves of RNA 1 of two strains of barley
      mild mosaic virus.
AB  - DNA complementary to the 3'-terminal halves of RNA 1 of two strains of barley
      mild mosaic virus (BaMMV) from Japan, BaMMV-Ka1 and BaMMV-Na1, was cloned and
      sequenced. The sequences start within a single long open reading frame (ORF), and
      are followed by 337 and 338 3' non-coding nucleotides, for BaMMV-Ka1 and BaMMV
      Na1 respectively. The two strains have 88% nucleotide identity in the ORFs and
      92% identity in the non-coding regions. The putative ORF products contain the
      capsid proteins at the C termini, as indicated by amino acid sequence analysis,
      and two putative non-structural proteins are arranged in the same manner as in
      RNA 1 of barley yellow mosaic virus (BaYMV). The deduced capsid proteins of BaMMV
      Ka1 and BaMMV-Na1 each contain 251 amino acids and have 94% sequence identity,
      which is compatible with their close serological relationship. Most of the
      sequence differences between the two capsid proteins are found in the N-terminal
      region, and might explain their serological differences. Significant sequence
      similarities of the capsid proteins of the two BaMMV strains (37 and 35%
      respectively) with that of BaYMV, and their marginal similarities (21 to 26%) to
      the capsid proteins of aphid-borne or mite-borne potyviruses support the
      classification of BaMMV and BaYMV as distinct members of the same virus group,
      which is separate from the group(s) containing aphidborne or mite-borne
      potyviruses.

PMID- 1402811
TI  - The nucleotide sequence of RNA-2 of raspberry ringspot nepovirus.
AB  - The nucleotide sequence of raspberry ringspot nepovirus (RRV) RNA-2 consists of
      3928 nucleotides and a poly(A) tract at the 3' end. RNA-2 contains one open
      reading frame which encodes a polypeptide of M(r) 123508 (123K). Edman
      degradation located the N terminus of the coat protein 514 residues from the C
      terminal end of the 123K protein, which suggests that the coat protein is
      released from the polyprotein by cleavage of a C-A bond. The RRV coat protein has
      some sequence similarities with the coat proteins of other nepoviruses, but is no
      more like any one nepovirus than another. In contrast, the portion of the 123K
      protein to the N-terminal side of the coat protein is similar in sequence to the
      corresponding parts of the polyproteins of tomato black ring and grapevine chrome
      mosaic nepoviruses, though not to those of other nepoviruses.

PMID- 1402812
TI  - Measles virus from a long-term persistently infected human T lymphoblastoid cell
      line, in contrast to the cytocidal parental virus, establishes an immediate
      persistence in the original cell line.
AB  - To investigate the mechanisms of measles virus (MV) establishment and maintenance
      of persistence in lymphoid cells, we have established a long-term persistent
      infection with MV, Edmonston strain, in the human T lymphoblastoid cell line
      MOLT4, which has been in continuous culture for over 8 years. In this culture,
      designated MOMP1, more than 98% of cells display viral antigens. The MOMP1
      culture is immune to superinfection with MV and is not cured by anti-MV
      antibodies. No evidence of defective interfering particles was obtained. The
      persistently infected culture releases an infectious virus showing a miniplaque
      and thermoresistant modified phenotype that, unlike the parental virus Edmonston
      strain which produces a lytic infection with extensive cell fusion, establishes
      an immediate persistence in MOLT4 cells with neither significant loss of cell
      viability nor cell fusion. This suggests that the modification in the virus
      suffices to maintain the state of persistence without requiring a coevolution of
      the host cell during the infection, as has been reported in other persistent
      virus infections.

PMID- 1402813
TI  - Measles virus gene expression in lytic and persistent infections of a human
      lymphoblastoid cell line.
AB  - MOMP1 is a measles virus (MV) long-term steady-state persistently infected
      culture of the human T lymphoblastoid cell line MOLT4. The analysis of MV gene
      expression revealed that in MOMP1 cells, the major MV proteins, haemagglutinin
      (H), phosphoprotein (P), nucleoprotein, fusion (F) and matrix (M), are present
      and the fusion precursor (F0) is cleaved into F2 and F1 peptides. H and F2
      proteins are glycosylated in both lytic and persistent MOLT4 infections. All
      major proteins are underexpressed in the persistently infected cultures in
      comparison to the lytically infected cells. However a relatively greater
      reduction was observed for H, M and P proteins. Pulse-chase labelling experiments
      indicated that this underexpression of H, M and P proteins was not due to
      selective degradation of these proteins in the persistent infection (p.i.). The
      relative amounts of the major monocistronic and dicistronic mRNAs for MV
      proteins, with the exception of P mRNA, was not altered in the p.i. with respect
      to lytically infected MOLT4 cells, suggesting that the defective expression of H
      and M proteins was not due to a restriction in the transcription of their mRNAs.
      In contrast, the mRNA for P protein, the most abundant MV mRNA in these lytically
      infected T lymphoid cells, is markedly underexpressed in the homologous p.i. Thus
      the underexpression of P protein in p.i. could be due to a decreased availability
      of P mRNA. This unbalanced underexpression of MV proteins may impair the cell
      fusion and c.p.e. of MV and facilitate viral persistence in human lymphoid cells.

PMID- 1402814
TI  - Mutagenesis of the L protein encoded by Bunyamwera virus and production of
      monospecific antibodies.
AB  - Bacterial fusion proteins containing portions of the Bunyamwera virus L protein
      were used as immunogens to prepare antisera in rabbits. Of five fusion proteins
      injected into rabbits, three yielded sera that reacted with the Bunyamwera virus
      L protein, detected by Western blotting or immunoprecipitation. Two of these
      antisera were specific for either the amino- or carboxy-terminal regions of the L
      protein. The specificity of these antisera was confirmed by their pattern of
      reactivity with full-length and truncated forms of the L protein. Plasmids
      containing the L gene cDNA under control of a bacteriophage T7 promoter were
      transfected into CV-1 cells which had previously been infected with a recombinant
      vaccinia virus, vTF7-3, that expresses T7 RNA polymerase. Antigenically authentic
      L protein was expressed. Using a nucleocapsid transfection assay developed
      previously, we showed that the transiently expressed L protein had RNA synthesis
      activity. Site-specific mutations were made in the L cDNA-containing plasmid to
      change certain amino acids in the putative polymerase domain of the L protein.
      The effects of these amino acid substitutions on the RNA synthesis activity of
      the L protein were monitored using the nucleocapsid transfection assay. These
      experiments showed that residues strictly conserved between the L proteins of
      different viruses in the family Bunyaviridae were obligatorily required for
      activity, whereas non-conserved residues could be substituted without abolishing
      RNA synthesis capability. Our results provide direct evidence for the functional
      significance of particular amino acids in the polymerase domain of a negative
      strand virus RNA polymerase.

PMID- 1402815
TI  - Organization of Germiston bunyavirus M open reading frame and physicochemical
      properties of the envelope glycoproteins.
AB  - We describe the construction of plasmids which express fusion proteins
      representing various regions of Germiston virus M polyprotein. The fusion
      proteins were purified and inoculated into rabbits to produce antisera. The N-
      and C-terminal regions of the polyprotein induced specific antibodies which
      reacted with glycoproteins G2 and G1, respectively, and the intermediate region
      induced antibodies against the NSM polypeptide. This enabled us to determine the
      gene order: G2-NSM-G1. Glycoproteins G1 and G2 form the spikes on the surface of
      the virion. We attempted to determine the structural organization of the
      glycoproteins by using a membrane-permeable cross-linking reagent, dimethyl
      suberimidate, but were unable to demonstrate that G1 and/or G2 form oligomeric
      structures. We analysed the glycoproteins further and showed that, like
      peripheral membrane proteins, the G2 and NSM proteins are almost completely
      extracted into the aqueous phase of detergent Triton X114-treated cellular
      extracts, whereas glycoprotein G1 is distributed in almost equal proportions
      between the aqueous and the detergent fractions. This indicates that G1 is a
      membrane-associated protein, but its presence in the aqueous phase suggests that
      it is less hydrophobic than a typical membrane protein. We have also
      characterized the intracellular transport of the envelope glycoproteins from the
      endoplasmic reticulum to the Golgi complex. Pulse-chase labelling followed by
      immunoprecipitation and treatment with endoglycosidase H (endo H) showed that
      both G1 and G2 are transported from the endoplasmic reticulum to the Golgi
      complex. Conversion to the endo H-resistant form is a rather slow process which
      takes more than 2 h. The mature G1 and G2 proteins present in the virion particle
      contain almost completely endo-H-resistant glycans.

PMID- 1402816
TI  - Non-random reassortment between the tripartite RNA genomes of La Crosse and
      snowshoe hare viruses.
AB  - The process of reassortment between the tripartite RNA genomes (segments
      designated L, M and S) of snowshoe hare and La Crosse bunyaviruses (Bunyaviridae)
      has been investigated by polymerase chain reaction analysis of greater than 250
      progeny recovered at 72 h post-infection from dual wild-type virus infections
      involving high multiplicities (approximately 5) of each virus in a BHK-21 cell
      line. Statistical analysis of the data indicated that RNA segment reassortment
      was not random, and for these two viruses the data appeared to fit the hypothesis
      that there was a preference for homologous L-M and M-S associations among the
      progeny formed.

PMID- 1402817
TI  - Human T cell leukaemia virus type 1 p21X mRNA: constitutive expression in
      peripheral blood mononuclear cells of patients with adult T cell leukaemia.
AB  - Although the p21X protein of human T cell leukaemia virus type 1 (HTLV-1) is
      generally thought to be expressed from a doubly spliced mRNA transcript (tax/rex
      mRNA) that encodes the p40tax, p27rex and p21X proteins, we have shown previously
      that a novel, alternatively spliced mRNA transcript (p21X mRNA) is responsible
      for p21X production in HTLV-1-infected cell lines. In the present study, we
      analysed expression of p21X mRNA and tax/rex mRNA in uncultured and cultured
      peripheral blood mononuclear cells (PBMCs) from eight patients with adult T cell
      leukaemia by using a quantitative polymerase chain reaction coupled to reverse
      transcription. The results demonstrated that the expression of p21X mRNA occurs
      constitutively in all uncultured and cultured PBMCs, whereas the expression of
      tax/rex mRNA is inducible in the cultured PBMCs, as described previously. In
      uncultured and cultured PBMCs from the one specimen in which p21X mRNA was highly
      expressed, the p21X protein was detectable by Western blotting. On the other
      hand, p27rex protein was detectable only after cultivation. These findings
      indicate that p21X mRNA is constitutively expressed in vivo and is responsible
      for production of p21X protein.

PMID- 1402818
TI  - The cloning, sequencing and expression of a major antigenic region from the
      feline calicivirus capsid protein.
AB  - RNA purified from the feline calicivirus (FCV) F9 vaccine strain was used to
      prepare a cDNA library in the expression vector lambda gt11. The library was
      screened for expression of FCV antigen using a rabbit antiserum prepared against
      purified FCV. A 330 bp cDNA clone was identified and used as a probe to obtain a
      larger overlapping clone of 1369 bp. Comparative sequence analysis with the CFI
      and F4 strains showed that the clones were derived from the 3' open reading frame
      encoding the capsid protein. The region encoded by the 330 bp clone was shown to
      be variable in the three strains compared, and therefore the probable location of
      major antigenic variation. This clone was expressed in a bacterial system and
      antiserum to the recombinant protein was used in immunoblots to confirm that this
      clone was derived from the gene encoding the capsid protein. From these
      immunoblots, several other capsid-related polypeptides were identified.
      Comparison with immunoblots using post-vaccination cat sera showed the antibody
      response in the cat was directed mainly against the capsid protein. Antiserum to
      the recombinant protein was shown to be effective in neutralizing the infectivity
      of FCV, indicating that at least one major neutralizing epitope had been cloned.

PMID- 1402819
TI  - Sequence comparison between the phosphoprotein mRNAs of human and bovine
      respiratory syncytial viruses identifies a divergent domain in the predicted
      protein.
AB  - The nucleotide and deduced amino acid sequences of the phosphoprotein (P) mRNA of
      bovine respiratory syncytial virus (BRSV) strain A51908 have been determined. The
      P mRNA is 860 nucleotides long with a single large open reading frame and the
      encoded polypeptide is 241 amino acids long. Comparison with the corresponding
      sequences of human respiratory syncytial virus (HRSV) subgroups A and B revealed
      72 to 74% identity at the nucleotide level, and 81% at the amino acid level. The
      P protein contains a single divergent domain (37% amino acid identity) flanked by
      highly conserved domains (87% amino acid identity). The 3' end non-coding region
      is 47 nucleotides shorter than the corresponding region of HRSV. Comparison of
      the P mRNA sequences of two strains of BRSV (A51908 and FS-1) showed that there
      was extensive sequence identity at both the nucleotide (97%) and amino acid
      (97.9%) levels.

PMID- 1402821
TI  - Two novel viruses associated with severe disease symptoms of the green stinkbug
      Nezara viridula.
AB  - Two viruses were isolated from green stinkbugs (Nezara viridula) with severe
      disease symptoms. These viruses have been named N. viridula virus type 1 (NVV-1)
      and NVV-2 according to their relative sedimentation coefficients. NVV-1 is a
      small picorna-like virus with a diameter of 29 nm, a buoyant density in CsCl of
      1.34 g/ml and a sedimentation coefficient of 153S. NVV-1 particles contain a 9.4
      kb ssRNA segment and have three coat proteins of M(r)s 32,100, 31,500 and 30,700.
      NVV-2 sediments as two components on sucrose gradients; the top 104S component
      consists almost entirely of 41 nm empty capsids and the faster sedimenting 177S
      component consists of intact 39 nm spherical particles. NVV-2 particles have a
      buoyant density in CsCl of 1.39 g/ml and consist of one major protein of M(r)
      73,800 and at least two minor proteins of M(r)s 13,500 and 16,500. Only one dsRNA
      segment of 6.2 kb was identified. The properties of NVV-2 are similar to those of
      the Totiviridae. Individual stinkbugs were infected with either NVV-1 or NVV-2,
      or with a mixture of the two viruses. Re-infection of virus-free stinkbugs with
      the mixture resulted in typical disease symptoms. Both viruses were vertically
      transmitted through the eggs and insects were infected by surface contamination
      of their food source.

PMID- 1402820
TI  - Expression of human endogenous retroviral sequences in peripheral blood
      mononuclear cells of healthy individuals.
AB  - The polymerase chain reaction was used to detect expression of retroviral
      sequences with oligonucleotide primers derived from conserved regions of the
      retroviral genome. Four primer pairs derived from gag and one from pol were used
      in amplification of reverse-transcribed total RNA prepared from peripheral blood
      mononuclear cells of seven blood donors. The amplification pattern was the same
      from each of the seven samples. Sequencing of cloned amplification products
      revealed that at least three subclasses of sequences related to the human
      endogenous retroviruses (HERV) RTVL-H, HERV-E and HERV-K, are expressed in
      peripheral blood mononuclear cells of healthy individuals. This has not been
      previously reported.

PMID- 1402822
TI  - The nucleotide sequence of red clover mottle virus bottom component RNA.
AB  - The complete nucleotide sequence of the bottom component RNA (B RNA) of red
      clover mottle virus strain S has been determined. The sequence consists of 6033
      nucleotides and contains a single long open reading frame sufficient to encode a
      protein of M(r) 210,258. The proteolytic processing sites within this protein
      have been deduced by comparison of its sequence with that of the B RNA-encoded
      protein of cowpea mosaic virus. Comparison of the amino acid sequences of the
      individual proteins confirms that the two viruses have a similar genome
      organization.

PMID- 1402823
TI  - A comparative study of the RNA-2 nucleotide sequences of two sweet clover
      necrotic mosaic virus strains.
AB  - The nucleotide sequences of the RNA-2s of two strains of sweet clover necrotic
      mosaic virus (SCNMV-38 and -59) have been determined. The RNA-2s of SCNMV-38 and 
      59 consist of 1446 and 1449 nucleotides, respectively, and both contain one major
      open reading frame (ORF) which potentially can encode polypeptides of 326 amino
      acid residues (about 36.5K), designated SC38P2 and SC59P2, respectively. The
      nucleotide sequences of SCNMV-38 and -59 RNA-2s show 93.2% similarity, and the
      amino acid sequences of SC38P2 and SC59P2 are 91.7% identical, although the
      identical nucleotides and amino acids are not distributed uniformly in RNA-2 and
      the encoded proteins. Two highly conserved regions (from positions 23 to 221 and
      297 to 326) and a relatively divergent region (from positions 222 to 296) are
      found in the P2 proteins of these strains. A similar pattern is apparent on
      comparison of the nucleotide and deduced amino acid sequences of RNA-2 of these
      SCNMV strains with those of the Australian and Czechoslovakian isolates of red
      clover necrotic mosaic virus.

PMID- 1402824
TI  - Phytohemagglutinin and concanavalin A activate hepatitis B virus in peripheral
      blood mononuclear cells of patients with chronic hepatitis B virus infection.
AB  - Peripheral blood mononuclear cells (PBMC) from 25 patients with chronic hepatitis
      B were tested for the presence of free monomeric hepatitis B virus (HBV) DNA
      migrating as a single 3.2 Kb band by Southern blot analysis. The PBMC were
      cultured for 7 days in the presence of phytohemagglutinin (PHA) or concanavalin A
      (ConA) both of which yielded a proliferative response. By contrast, both
      bacterial lipopolysaccharide (LPS) and interleukin 2 (IL2) failed to do so. Dot
      blot assays were used to monitor HBV DNA level increase within PBMC. Following
      mitogen exposure HBV DNA levels increased above pre-stimulation levels in 19/25
      PHA cultures, 6/15 ConA cultures, 1/15 LPS cultures, and 1/15 IL2 cultures. In 15
      patients, Southern blot analysis was carried out before and after PHA exposure.
      In 13/15 cases, a single 3.2 Kb band was observed in unstimulated cultures as
      well as in PHA cultures even though PHA induced a HBV DNA increase. One case
      exhibited bands migrating faster than the 3.2 Kb signal, compatible with
      replicating intermediates and one case provided evidence of viral concatemers
      within PBMC after PHA stimulation. No HBV DNA was detected in the culture
      supernatants. The increase of HBV DNA level in PBMC induced by mitogen was
      strongly associated with an increase in HBV DNA expression (HBV RNA and HBs
      antigen). These studies indicate that HBV DNA present in human PBMC does
      represent a potential reservoir for infection with endogenous reactivation
      following PBMC activation.

PMID- 1402825
TI  - Enteric non-A, non-B hepatitis: epidemics, animal transmission, and hepatitis E
      virus detection by the polymerase chain reaction.
AB  - We studied epidemics of viral hepatitis occurring at three different places in
      India. One was a combined epidemic due to hepatitis E virus (HEV) and hepatitis A
      virus (HAV) infections. In this epidemic, HAV affected children below 10 years of
      age, whereas HEV infected the young adult population. HEV was transmitted to
      rhesus monkeys (Macaca mulata) and confirmed by the polymerase chain reaction
      (PCR) on bile from the animals. Fecal material from acutely infected patients in
      one of the epidemics was also found positive for HEV RNA by PCR. This may help in
      confirming the nature of future epidemics. The bile and liver from experimental
      animals can be used as a source of material for further virological and molecular
      biological studies of HEV.

PMID- 1402826
TI  - Acute sporadic hepatitis E in children living in Cairo, Egypt.
AB  - Seventy-three pediatric patients with acute hepatitis and 19 control patients
      without liver disease living in Cairo, Egypt, were evaluated with a newly
      developed Western blot assay for IgM antibody to hepatitis E virus (IgM anti
      HEV). The mean age of acute hepatitis patients was 6.4 years (range, 1-13 years);
      56% were male. Among the 73 acute cases, hepatitis A was diagnosed in 30 (41%),
      possible acute hepatitis B in three (4%), hepatitis E in nine (12%), and by
      exclusion, non-A, non-B hepatitis in 29 (40%). Two additional acute cases were
      positive for both IgM anti-HAV and IgM anti-HEV. None of the 19 control subjects
      had IgM anti-HEV. Parenteral risk factors were associated with cases of non-A,
      non-B hepatitis but were not associated with acute hepatitis E. Contact with a
      family member with jaundice was associated with acute hepatitis A. In contrast to
      prior epidemics of enterically-transmitted non-A, non-B hepatitis, HEV was found
      to be a common cause of acute hepatitis in a pediatric population. This study
      provides additional evidence that HEV may be a frequent cause of acute sporadic
      hepatitis among children living in some developing countries.

PMID- 1402827
TI  - Concurrent hepatitis C virus and hepatitis delta virus superinfection in patients
      with chronic hepatitis B virus infection.
AB  - Since hepatitis C virus (HCV) and hepatitis delta virus (HDV) are transmitted by
      the same routes as hepatitis B virus (HBV), simultaneous or concurrent HCV and
      HDV infection in patients with chronic HBV infection may occur. To test this
      hypothesis and to examine the clinicohistological and immunopathological
      presentations of such multiple hepatitis virus infections, acute and/or
      convalescent serum specimens from 86 patients with acute HDV superinfection were
      tested by enzyme immunoassay for antibodies to HCV. Of the 86 patients, 18
      (20.9%) were associated with HCV infection. Although patients with early
      mortality cannot be evaluated by the HCV markers used in this study, the results
      showed that the clinical and histologic features were similar except that
      patients with HCV infection were older than those without HCV infection (P less
      than 0.01). Immunopathological studies carried out within 2 months after the
      onset of acute HDV superinfection demonstrated that hepatitis B core antigen
      (HBcAg) was not detected in any patient and HDV antigen was detected in 18.2% of
      the patients with HCV infection whereas HBcAg and HDAg were found in 7% and
      65.1%, respectively, of those without HCV coinfection (P less than 0.02). It is
      concluded that concurrent HCV and HDV superinfections can and do occur in
      patients with chronic HBV infection. In these triple viral infections, HCV may
      even transiently suppress HDV and HBV.

PMID- 1402828
TI  - Dideoxyinosine for chronic hepatitis B infection.
AB  - Six patients positive for both human immunodeficiency virus (HIV) and hepatitis B
      were studied to assess the effect of dideoxyinosine (DDI) on hepatitis B virus
      (HBV) replication. Two patients died during the follow-up period and four had at
      least 8 weeks of therapy. One patient demonstrated HBV DNA suppression and became
      transiently negative. In the remaining five patients, there was no appreciable
      change in HBV DNA levels during DDI therapy. DDI was well tolerated in all
      patients, the only significant side effect being diarrhoea. It is concluded that
      DDI has no notable antiviral effect in patients with chronic HBV infection when
      coinfected with HIV.

PMID- 1402829
TI  - Prevalence of serum antibodies against lymphocytic choriomeningitis virus in
      selected populations from two U.S. cities.
AB  - An ELISA was developed for measuring serum antibodies against the arenavirus
      lymphocytic choriomeningitis virus (LCMV) and a closely related isolate termed
      callitrichid hepatitis virus (CHV). The ELISA was used to test sera from healthy
      adults and from hepatitis patients. In Birmingham, Alabama, the seropositivity
      rate for healthy black women was 5.1% (7/138), and the rate for patients with all
      types of hepatitis or cirrhosis was 4.3% (2/46). In San Antonio, Texas, the
      seropositivity rate among a clinical series of patients with non-A, non-B
      hepatitis was 0 (0/20), and the rate among persons rejected from blood donation
      because of high serum alanine aminotransferase levels was 2.4% (2/82). These
      results indicate that infection with LCMV or CHV is common in Birmingham but that
      infection is not associated with hepatitis.

PMID- 1402830
TI  - Sexual transmission of human T-lymphotropic virus type I in Peruvian prostitutes.
AB  - The epidemiology of HTLV-I infection in female prostitutes was studied in a
      survey of 395 prostitutes from Callao, Peru (the port city of Lima), 72
      prostitutes from Iquitos, Peru (another port city on the Amazon River), and 510
      prenatal clinic patients from Lima. Prostitutes reported a mean of 8.8 years
      (range, 1-39 years) of active prostitution and a mean of 205 sexual contacts
      during the month prior to the study. The percentage of prostitutes with HTLV-I
      antibody (21.8%) was significantly higher than patients attending a prenatal
      clinic (3.1%; P less than .0001). The prevalence of HTLV-I antibody increased
      steadily with age in prostitutes, but no age trend was noted in prenatal
      patients. By multiple logistic regression analysis, an independent association
      was found between HTLV-I seropositivity and a history of prostitution in Callao,
      age, and positive syphilis serology when all 977 study subjects were evaluated.
      When prostitutes alone were analyzed, the number of years of exposure as a
      practicing prostitute was associated with HTLV-I seropositivity after controlling
      for age. These data indicate a greatly increased risk of HTLV-I infection in
      prostitutes in Callao, Peru, and suggest an association between sexual activity
      and HTLV-I transmission.

PMID- 1402831
TI  - HIV-2 infections in a rural Senegalese community.
AB  - In a community study in rural Senegal, 22 human immunodeficiency virus type-2
      (HIV-2) seropositive cases and 64 matched controls were examined clinically and
      evaluated immunologically. The presence of clinical signs was highly correlated
      with HIV-2 seropositivity: 9 anti-HIV-2 positive patients and 5 controls
      presented with clinical signs (odd ratio [OR] = 8.2, confidence limits [CL] 2
      35). The main symptom associated with HIV-2 seropositivity was a chronic cough
      (OR = 18.5, CL 1.8-899). The presence of diarrhoea was not significant (OR = 3.1,
      CL 0.3-3.5). The total number of CD8 cells, CD4/CD8 ratio, beta 2 microglobulin,
      and IgG level discriminated between seropositive and seronegative individuals (P
      less than 0.05). When the anti-HIV-2 positives were grouped as 13 healthy and 9
      sick people, red blood cells, lymphocytes, T lymphocytes, CD4 cells, and beta 2
      microglobulin differed significantly. Clinical symptoms were associated with
      immunodepression: 5 of 14 sick people had less than 500 CD4/microliters vs. 1 of
      72 healthy persons. This study at the community level emphasizes the clinical and
      immunological impact of HIV-2 infection. Even if it presents with a longer
      incubation period than HIV-1, this virus is a major threat to public health.

PMID- 1402832
TI  - Dependency conflict, marital threat, and alcohol consumption in a middle-aged
      sample.
AB  - The hypothesis that dependency conflict is associated with higher levels of
      alcohol consumption when dependency needs are threatened or thwarted was tested
      with a sample of 672 middle-aged, married adults with college-age children. The
      subjects' current level of alcohol consumption was predicted based on the present
      level of threat to the marital relationship (assessed by reports from several
      family members) and on indices of dependency need and inhibition of dependent
      behavior estimated from sibship size, sibship density, and sibling position. A
      multiple regression analysis yielded a significant two-way interaction (p less
      than .05) between marital threat and subject sex, and a significant three-way
      interaction of dependency need, inhibition of dependent behavior, and marital
      threat. High marital threat was associated with higher levels of alcohol
      consumption in men and slightly lower levels of alcohol consumption in women.
      Additionally, when dependency need was high, alcohol consumption was generally
      low, except when both inhibition of dependent behavior and marital threat were
      high. However, when dependency need was low, the highest alcohol consumption
      score occurred when marital threat was low and inhibition was high.

PMID- 1402833
TI  - Using a personal robot to teach young children.
AB  - Seventy-five preschool children were instructed about birds by a human teacher, a
      moving personal robot, a stationary personal robot, and a tape recorder. How much
      the children learned and how much attention the children paid were compared for
      each type of instruction. The children learned when they were taught by the human
      teacher and when they were taught by the animated and the stationary robots. The
      children paid more attention to the live teacher and to the moving robot than
      they did to the stationary robot or to the tape recorder. The difference between
      the amount of attention the children paid to the animated robot and the amount of
      attention they paid to the human teacher was not statistically significant.

PMID- 1402834
TI  - Adjustment problems experienced by children during cross-cultural orientation: a
      pilot study.
AB  - A study was undertaken to investigate the adjustment problems of children aged 8
      10 years when they relocated from their native countries to Vienna, Austria.
      There was a moderate correlation between anxiety and adjustment to changes in the
      physical and material environment and a significant correlation between anxiety
      and changes in social support systems. Adjustment to changes in parental behavior
      and changes in language demands both showed a low negative correlation with
      anxiety. Children who had spent the least time in Vienna showed greater evidence
      of anxiety and stress than did children who had lived in the city for at least 1
      year.

PMID- 1402835
TI  - Popular and rejected children's social reasoning: linking social status and
      social knowledge.
AB  - The relationship between children's social status/sex and their moral judgements
      was examined. Sixty-four second- and third-grade children (33 boys, 31 girls) who
      were identified as popular or rejected by peer sociometric measures were shown
      pictures of children engaged in moral and second-order transgressions. The
      children were asked to rate each event on (a) the degree of seriousness for other
      and self, (b) the amount of punishment for other and self, and (c) rule
      alterability. The children were also asked for justification of the
      transgressions (why they thought the transgressions were wrong). The popular and
      rejected children differentiated between moral and second-order transgressions
      based upon criterion ratings and justifications. Differences emerged between the
      popular and the rejected children's ratings and justifications for moral
      transgressions, suggesting that children's moral judgements are related to social
      experiences associated with peer acceptance and rejection.

PMID- 1402836
TI  - Mothers with hostile, Type A predisposing child-rearing practices.
AB  - The authors examined characteristics of Finnish mothers (N = 924) who use hostile
      child-rearing practices (i.e., they ignore the child, are punitive and irritable,
      and perceive the child as a burden), practices that have been shown (Raikkonen &
      Keltikangas-Jarvinen, 1992) to predispose children to Type A behavior. The
      results of this study indicate that two factors--Type A behavior in the mothers
      and the mothers' sociodemographic background (low occupational status, low
      educational level and young age)--increase the probability of the mothers'
      treating their children in a hostile manner. Also, the mothers of boys in this
      study reported more hostile child-rearing practices than the mothers of girls
      did.

PMID- 1402837
TI  - Locus of control and time orientation in daydreaming: implications for therapy.

PMID- 1402838
TI  - Guidelines for developing, evaluating, and revising the classification of
      personality disorders.
AB  - The authors suggest ways to improve the classification of personality disorders
      by changing the way the classification is developed, evaluated, and modified.
      Specific proposals are intended to establish a system that can be evaluated and
      revised so that it successively approximates a valid system. The importance of
      stating the principles underlying the classification is emphasized. These
      principles include: the conception of personality disorder underlying each
      diagnosis, the structure used to define diagnoses, the nature of diagnostic
      items, and the model for organizing diagnostic decisions. A distinction is drawn
      among the theoretical, measurement, and diagnostic models underlying each
      diagnosis. The substantive aspects of the classification are discussed in terms
      of the evidence required to validate diagnostic concepts. It is argued that the
      first step in developing a classification is to ensure the content validity of
      diagnostic concepts because this is a prerequisite for other components of
      validity. Evaluation and revision of the classification are discussed in terms of
      the importance of convergent and discriminant evidence. It is recommended that
      the classification be evaluated and revised using criteria derived from the
      theoretical and measurement models associated with each diagnosis. It is also
      recommended that the classification be evaluated in terms of the degree to which
      diagnostic constructs are consistent across clinicians, different sets of
      diagnostic exemplars, and different samples of patients. Realization of these
      aims should provide a classification that may be verified, modified, or disproved
      in the scientific tradition.

PMID- 1402839
TI  - Gender roles and alcohol abuse. Costs of noncaring for future physicians.
AB  - Psychiatric epidemiological research has focused disproportionate attention on
      traditionally female disorders such as depression. This paper shifts
      epidemiological gears to elaborate and test an etiological model of a
      traditionally male disorder, that of alcohol abuse. We argue that social
      relational deficits (narcissistic orientations) lead to abuse of alcohol for
      stress reduction purposes, given interpersonally oriented stressors and the
      incapacity to form social supports. The model was tested in the context of
      training for a traditionally male occupation encompassing both social-relational
      demands and limited social supports. A cohort of medical students was surveyed
      from medical school entrance through a portion of clinical training. Time 1
      social-relational deficits were predictive of time 3 alcohol abuse, partially as
      a function of social support deficits and, to a lesser extent, patient care
      related stressors. Moreover, there was an initial gender difference in social
      relational deficits and a trend-level gender difference in alcohol abuse that
      disappeared when social-relational deficits were held constant. By time 3, women
      did not differ from men in social-relational deficits or alcohol abuse.

PMID- 1402840
TI  - Manifestation of depressive symptoms among adolescents. A comparison of Mexican
      Americans with the majority and other minority populations.
AB  - The purpose of this research was to investigate differential manifestation of
      depressive symptomatology among adolescents from diverse ethnocultural groups.
      Data from a national survey of persons 12 to 17 years of age (N = 2200) were
      analyzed, comparing responses of Anglo, African, Mexican, and other Hispanic
      Americans with a 12-item version of the Center for Epidemiologic Studies
      Depression Scale. The results indicated minimal differences in terms of item
      response and internal consistency-reliability among the four adolescent groups.
      However, there were differences in patterns of item endorsement, as indicated by
      principal component factor analysis. Anglo- and African Americans exhibited
      similar factor structure, represented by negative affect, positive affect, and
      psychosomatic symptoms. The two Hispanic groups also exhibited a three
      dimensional pattern, but there was a tendency among Hispanic adolescents for
      somatic symptoms and negative affect symptoms to cluster together. This pattern
      may indicate a more prominent role of somatic complaints in the presentation of
      depression among Mexican Americans and other Hispanics.

PMID- 1402841
TI  - Changes in ego defenses with recovery from depression.
AB  - This study aimed to determine whether patterns of ego defense change with short
      term treatment of psychiatric illness. The subjects were 37 inpatients and
      outpatients with a DSM-III-R diagnosis of major depressive disorder being treated
      using standard clinical methods. Ego defenses before and 7 to 9 weeks after
      commencement of treatment were measured using a shortened version of the Defense
      Style Questionnaire. There was a significant decline in the use of immature
      defenses with symptomatic recovery, but no change in the neurotic or mature
      defenses. Patients with additional axis I diagnoses and/or abnormal personality
      traits (N = 15) used more neurotic defenses than their counterparts with major
      depression alone (N = 22), but this pattern did not change with time. The study
      demonstrates the short-term mutability of immature defenses in relation to an
      episode of psychiatric illness and provides empirical support for the concept of
      temporary regression in the context of psychiatric illness episodes.

PMID- 1402842
TI  - Observational measurement of symptoms responsive to treatment of major depressive
      disorder in children and adolescents.
AB  - Observational methods were used to determine whether depressive symptoms in 20
      inpatients with major depressive disorder could be observed to change during the
      course of treatment with antidepressant medication. Four consecutive weekly
      observation sessions were done using the Emotional Disorders Rating Scale, which
      collects information about symptoms of depression, mania, anxiety, hostility, and
      irritability. Only those scales indexing depressive symptoms evidenced change.
      Significant change was observed between the third and fourth weeks of
      hospitalization, thereby replicating the findings reported in the adult
      literature regarding depressive symptoms' responsiveness to antidepressants.

PMID- 1402843
TI  - Season of birth and neuropsychological impairment in schizophrenia.
AB  - Repeated studies suggest a relationship between winter birth and increased
      incidence of schizophrenia. Furthermore, there may be seasonal fluctuations in
      schizophrenia risk factors (e.g., influenza epidemics) and the severity of
      biological anomalies (e.g., enlarged cerebral ventricles in neuroimaging
      studies). In order to assess whether winter-born schizophrenics show greater
      neuropsychological impairment, 112 males meeting Research Diagnostic criteria for
      schizophrenia were administered the Luria-Nebraska Neuropsychological Battery, a
      thorough measure of higher cortical functioning deficit. Sixty-four of these 112
      patients were also administered the Wechsler Adult Intelligence Scale-Revised,
      the Benton Visual Retention Test, and the Rey Auditory Verbal Learning Test.
      Despite the use of several definitions of winter and nonwinter birth, there was
      no evidence of elevated rates of neuropsychological dysfunction among winter-born
      patients on any measure. The current study contains certain limitations (e.g.,
      variable medication status at testing), but the results suggest no strong season
      of birth relationship with neuropsychological impairment in a reasonably large,
      research-diagnosed sample of schizophrenic patients.

PMID- 1402844
TI  - Psychophysiological processes during insight-oriented therapy. Further
      investigations into nonlinear psychodynamics.
AB  - Experimental evidence shows that many physiological processes abide by nonlinear
      dynamics and evidence chaos. Novel conceptual models postulate chaotic phenomena
      in psychological processes as well. The challenge in empirically testing these
      models is to develop measures that are sufficiently precise to permit nonlinear
      dynamical analyses and that also say something meaningful about psychological
      phenomena. Toward this end, we examined the spontaneously occurring autonomic
      activity of a patient during psychotherapy. Phase portraits were constructed of
      the patient's heart rate data for each of several therapy sessions. The flows
      within these phase spaces were visually segmented and assigned to one of four
      previously defined trajectory classifications. These trajectories were
      quantitatively analyzed, and the corresponding clinical material was assessed
      qualitatively. The trajectories in the physiological phase space were
      recognizable, recurrent, and robust; they appeared coupled to ongoing
      psychological processes. Possible refinements in this typology are discussed and
      suggestions are made for potentially using such analyses to track and navigate
      among psychophysiological states.

PMID- 1402845
TI  - Psychiatric diagnoses of abusive mothers. A preliminary report.
AB  - The Structured Clinical Interview for DSM-III-R diagnoses of 54 mothers who had
      maltreated their children were compared with those of 37 controls. The
      maltreatment group showed a significantly greater incidence of both current and
      past diagnoses. Maltreating mothers exhibited a significantly greater incidence
      of current mood disorder, alcohol abuse, and personality disorder than did
      controls. The results indicate that past abuse of cocaine, alcohol, other
      substances and past mood disorders were significantly more prevalent among the
      maltreatment sample than among controls. Mothers who had maltreated their
      children were significantly more likely to have histories of posttraumatic stress
      disorder than were controls.

PMID- 1402846
TI  - SPECT imaging and multiple personality disorder.

PMID- 1402847
TI  - Othello's syndrome and hyperthyroidism.

PMID- 1402848
TI  - Relationship of major life events and daily stressors to symptomatology in
      schizophrenia.

PMID- 1402849
TI  - Glucose metabolism in psychiatric disorders: how can we facilitate comparisons
      among studies?
AB  - Positron emission tomography (PET) offers a possibility to study brain function
      and its relationship to psychiatric disorders. Clinical studies have demonstrated
      that several psychiatric diseases are coupled with changes in brain glucose
      metabolism. Schizophrenia seems to involve a lower metabolism in wide areas of
      the brain--both cortical and subcortical structures. Depression probably involves
      dysfunction of the metabolism in dorsolateral prefrontal cortex. Obsessive
      compulsive disorder, panic disorder, anorexia nervosa and the experience of
      anxiety may involve increased metabolic rates. The results from the different
      studies do not allow quantitative comparisons or detailed analyses because of
      large differences in experimental and clinical methodology. The term Good
      Clinical PET Practice (GCPP) is suggested to encourage standardization in
      clinical investigations. GCPP includes standardization of both experimental
      factors (lumped constant, arterialization, purity of tracer, regions of interest,
      relative rates) and clinical factors (state of the subject, wakefulness, anxiety,
      gender, course of the disease) in PET performance.

PMID- 1402850
TI  - Operators and scales: diagnostic and rating issues in psychiatric PET research.
AB  - In psychiatric research that for various reasons has to restrict itself to a
      limited number of subjects, such as studies involving expensive positron emission
      tomography techniques, issues concerning the parsimonious description of patients
      gain in importance. The number of descriptive variables must be optimally small.
      This paper offers a conceptual back-ground for the choice of operators in
      operational diagnostic systems designed to delimit pathological types, and of
      rating scales designed to measure syndromal severity in a dimensional way. A
      practical suggestion in five tenets for the organization of clinical research of
      this kind is presented.

PMID- 1402852
TI  - On the influence of spatial resolution and of the size and form of regions of
      interest on the measurement of regional cerebral metabolic rates by positron
      emission tomography.
AB  - Factors that affect the accuracy of the positron emission tomographic (PET)
      quantification of cerebral metabolic rates include the spatial resolution of the
      employed imaging device and the method used for extraction of regional metabolic
      values from the PET data set. The present article reviews (i) how and to what
      extent these two factors are presumed to influence the measurement of absolute
      values of cerebral metabolic rates and their ratios, and (ii) whether and how
      these factors may affect comparisons of regional metabolic rates between groups
      of subjects.

PMID- 1402851
TI  - The FDG model and its application in clinical PET studies.
AB  - The FDG method, as it is applied in clinical PET studies is reviewed. The
      influence of different implementations of the method and instrumental
      inaccuracies on the values of cerebral metabolic rate of glucose is discussed.
      For the comparison of the results between different groups standardized
      procedures are recommended.

PMID- 1402853
TI  - The role of anatomic information in quantifying functional neuroimaging data.
AB  - When using modern neuroimaging tools, such as CT, PET, SPECT, MRI and MEG, in
      brain research and brain diagnostics, there is a common need for including
      external anatomical information into the interpretation and analysis of data.
      This information may be used to aid the interpretation of structures in images
      from low resolution imaging tools. With high resolution tools it can help to
      identify resolved structures. It can also facilitate the merging of data from
      different modalities, or from different individuals. The anatomical information
      is often given as regions of interests (ROIs), which may be manually created from
      an anatomy rich image or automatically created from a standard template
      collection or from an atlas data base. Automatic methods will lead to a
      substantial reduction in bias and in size of the systematic errors. Functional
      ROIs can correspondingly be derived from functional images (usually PET or
      SPECT). Different aspects of these processes are discussed in the report.

PMID- 1402854
TI  - The dorsolateral prefrontal cortex, schizophrenia and PET.
AB  - Central neurophysiology can be measured with PET. These measurements are
      providing insights into the regional abnormalities associated with schizophrenia.
      Cohorts of schizophrenic subjects have been studied cross-sectionally in attempts
      to identify common regional deficits. More recently the advent of fast dynamic
      measurements of regional cerebral blood flow have allowed rapid serial
      measurements in the same subject in different brain states (activation studies).
      These complementary approaches are based upon, and are interpreted with reference
      to, a number of methodological considerations and underlying hypotheses. The key
      hypotheses underpinning cross-sectional and activation studies are discussed
      within the framework of the lesion model and functional anatomy models of brain
      function. This brief review of some assumptions, ideas and methodological
      constraints is illustrated with empirical data implicating the dorsolateral
      prefrontal cortex in schizophrenic symptoms.

PMID- 1402855
TI  - Back to basics.
AB  - The basic strength of the AMCA family is the wide range of expertise and "can do"
      attitude of its diverse membership. The AMCA is currently experiencing problems
      with federal legislation and fiscal stability because we have not fully utilized
      member strengths to reevaluate the association's direction and set new goals to
      address change. However, the AMCA Board of Directors and many committee
      chairpersons met, reevaluated direction and clarified goals, and initiated major
      changes to meet the challenges facing the association and its members. Members of
      the AMCA are encouraged to contribute their individual talents to ensure that the
      association prosper and serve the needs of the mosquito and vector control
      family.

PMID- 1402856
TI  - Patrick Manson and the discovery age of vector biology.
AB  - There have been few scientists who have had a greater impact on the history of
      vector biology than Sir Patrick Manson (1844-1922). By demonstrating that
      mosquitoes became infected with microfilariae in the process of taking a blood
      meal, he became the first to prove an association between insects and pathogens
      causing human and animal diseases. He also contributed substantially to the
      discovery of mosquito transmission of malaria parasites and was a principal force
      behind the founding of the London School of Tropical Medicine and the Royal
      Society of Tropical Medicine and Hygiene. Manson's career is reviewed in
      historical context as well as in relation to modern concepts of vector biology.

PMID- 1402857
TI  - Influence of temperature and larval nutrition on the diapause inducing
      photoperiod of Aedes albopictus.
AB  - Photoperiod induced dormancy for 14 North American strains of Aedes albopictus
      were determined at 21, 26 and 29 degrees C. Strains tested at 21 degrees C and
      intermediate temperatures of 25-27 degrees C demonstrated clear photoperiodic
      responses whereas temperatures of 29 degrees C and above, greatly reduced or
      negated diapause incidence. A suboptimal larval diet increased the percentage
      diapause in eggs laid by resulting adults. This larval diet was also associated
      with a slight increase in critical photoperiod.

PMID- 1402858
TI  - Evaluation of methoprene (Altosid XR) sustained-release briquets for control of
      culex mosquitoes in urban catch basins.
AB  - A sustained-release, briquet formulation of methoprene (Altosid XR), applied at a
      rate of one briquet per catch basin in Saginaw, Michigan, provided ca. 70%
      reduction in emergence of Culex pipiens and Cx. restuans adults, compared with
      nontreated catch basins, during a period of 15 wk in the summer of 1990. In a
      parallel study using one briquet per 10.5 liter bucket, there was 99% reduction
      in adult emergence of these species for a period of 12 weeks. The difference
      between catch basins and buckets may be attributable to water movement through
      the catch basins with each rainfall, causing a dilution of methoprene through
      time. However, both studies indicated that the briquets released methoprene for
      12-15 wk, suggesting that this formulation may offer season-long control of Culex
      mosquitoes from urban catch basins in Michigan, with a single treatment of
      insecticide.

PMID- 1402859
TI  - Transmission of La Crosse virus by four strains of Aedes albopictus to and from
      the eastern chipmunk (Tamias striatus).
AB  - Eastern chipmunks were successfully infected with La Crosse virus by bites of 3
      New World strains of Aedes albopictus infected orally or transovarially. The
      virus was subsequently passed from the chipmunks to Ae. albopictus, POTOSI
      strain, and Ae. triseriatus. The chipmunks developed viremias of 1-4 days
      duration and antibody titers were similar in intensity and duration to those
      reported in chipmunks infected by Ae. triseriatus. After feeding on viremic
      chipmunks, Ae. albopictus became infected and transmitted La Crosse virus at
      rates similar to the native vector, Ae. triseriatus. Aedes albopictus transmitted
      La Crosse virus transovarially to first gonotrophic cycle offspring.

PMID- 1402860
TI  - Effect of ULV malathion on automotive paint finishes.
AB  - The relationship between malathion droplet size (VMD) and degree of damage to
      1990, 1K and 2K General Motors paint standards was investigated in the laboratory
      and field. Laboratory tests indicated a positive correlation between malathion
      droplet VMD and damage spot size. Laboratory settling chamber tests revealed that
      size-thresholds of droplets too small to cause visible damage averaged 8 and 11
      mu on washed 1K and 2K paints, respectively. Field tests indicated malathion
      caused no visible damage to 1K or 2K paint panels under routine operating
      conditions, although droplet sizes (VMD) sampled on the automobile surface
      averaged 10.2 +/- 4.5 and 11.7 +/- 5.7 mu. Microscopic damage was found on paint
      panels placed on the hood, roof, trunk and doors of the automobile when parked
      parallel or perpendicular to the course of the spray truck and when driven
      through the spray of a stationary spray truck.

PMID- 1402861
TI  - Comparative efficacy of aphid extracts and some juvenoids against the development
      of mosquitoes.
AB  - Comparative efficacy of natural juvenile hormones extracted from Aphis craccivora
      and A. gosypii and 5 juvenoids, i.e., methoprene, Neporex, OMS 3007, OMS 3019 and
      DPE-28 on the development of Aedes aegypti, Anopheles stephensi and Culex
      quinquefasciatus have been evaluated. OMS 3007, OMS 3019, DPE-28 and Neporex show
      species specific related activities, while methoprene and aphid extracts do not
      show such activity against these mosquito species. Treatment of mosquito eggs
      with an EC50 dose of these compounds caused mortality while an EC90 dose
      completely ceased adult emergence. The fecundity and fertility rates of
      mosquitoes emerged shows significant reduction (P less than 0.001) when treated
      with EC50 doses of all the compounds.

PMID- 1402862
TI  - Detection of human antibodies against Plasmodium falciparum antigens in blood
      meals of anopheline mosquitoes.
AB  - Human IgG antibodies against Plasmodium falciparum asexual stages, gametocytes
      and sporozoites were detected by indirect fluorescent antibody (IFA) techniques
      in the blood meals of Anopheles gambiae s.l. from a malaria-endemic area of
      western Kenya. Field-collected mosquitoes, which had been stored dry for over 2
      years, were screened first for human IgG by ELISA. In 141 blood meal samples from
      human-fed mosquitoes, the prevalence of stage-specific antibodies was 87.9% for
      asexual-stage parasites, 78.0% for gametocytes, and 87.9% for sporozoites. There
      were no differences in the prevalence of stage-specific antibodies for mosquitoes
      collected from 2 sites, before and after the long rainy season of 1988. The
      detection of specific human antibodies in mosquito blood meals by IFA, or by more
      efficient methods, may provide alternative approaches for large-scale,
      epidemiologic studies of malaria and other vector-borne diseases.

PMID- 1402863
TI  - Evaluation of different methods of catching anopheline mosquitoes in western
      Venezuela.
AB  - During a longitudinal study of vector biology and malaria transmission in western
      Venezuela, adult mosquitoes were collected by different methods and their
      efficiency was compared with human landing catches. CDC light traps, a double
      net, a calf-baited trap and collection of resting mosquitoes on vegetation were
      tested. These methods did not prove to be effective substitutes for human landing
      catches.

PMID- 1402864
TI  - Effect of Nosema algerae on the house fly Musca domestica (Diptera: Muscidae).
AB  - Larvae of Musca domestica were exposed to spores of Nosema algerae on the surface
      of their diet. Infective concentrations (IC50 and IC90) for the larvae were 3.6 x
      10(4) and 1.6 x 10(6) spores/cm2, respectively. The disease appeared to cause no
      larval mortality, but the longevity of adult females was reduced. At 30 days post
      infection, there were at least 1 x 10(7) spores per fly in all dosage groups. At
      lower dosages, the development of spores was delayed and fewer spores were
      produced.

PMID- 1402865
TI  - Lethal effects of ivermectin on Anopheles quadrimaculatus.
AB  - Female Anopheles quadrimaculatus adults were blood fed on 15 mixed breed dogs 4 h
      after the dogs were given oral dosages of ivermectin. Dogs were divided into 5
      treatment groups of 3 dogs each, at 10, 500, 1,000, 2,500 micrograms/kg, and
      untreated. Additionally, An. quadrimaculatus were fed on lambskin-membranes
      containing blood drawn from one dog in each treatment group. Mosquitoes were
      allowed to feed on the dogs or the lambskin-membranes and were observed for death
      at 24 and 48 h post-feeding. Greater than 90% mortality was recorded in all
      ivermectin treatment groups except at the 24 h post-feeding period with the 10
      micrograms/kg dog dose blood fed through the lambskin-membrane (65.4% mortality).
      The highest 2 dosages produced 100% mosquito mortality at 48 h post-feeding from
      either a dog or the in vitro system using a lambskin-membrane.

PMID- 1402866
TI  - Seasonal incidence and horizontal distribution patterns of oviposition by Aedes
      aegypti in an urban environment in Trinidad, west Indies.
AB  - The oviposition patterns of Aedes aegypti in ovitraps placed along 5 horizontal
      transects were monitored weekly for 52 wk (January to December 1988) in St.
      Joseph, Trinidad. Of the 2,550 ovitraps exposed, 270 were lost and 1,177 (52%)
      out of 2,280 were used by gravid females, containing 38,118 eggs. During the dry
      season 43% (16,265 eggs) of the eggs were collected whereas during the wet season
      57% (21,853 eggs) were collected. Ovitraps exposed under eaves, under houses and
      in the open yard attracted similar oviposition occurrences and proportions of
      eggs. Inspections of the 52 properties within St. Joseph revealed that 17 (House
      Index = 32.7%) harbored Ae. aegypti pre-adult stages. The container index was
      5.5%. This study revealed no evidence of behavioral changes in the container
      preferences of Ae. aegypti in St. Joseph, Trinidad, after 12 years of treating
      with fenthion and temephos.

PMID- 1402867
TI  - Sublethal effects of larval methoprene exposure on adult mosquito longevity.
AB  - Larvae of Aedes aegypti were exposed to sublethal concentrations of the insect
      growth regulator, methoprene, and the glycogen content of pupae and surviving
      adults was compared and effects on adult longevity determined. The glycogen
      reserves in both male and female Ae. aegypti pupae were significantly reduced as
      a result of methoprene exposure. The longevity of adult females was also
      significantly reduced, but exposure affected neither the longevity nor the
      glycogen content of adult males. Adult sugar feeding increased the amount of
      glycogen in both treated and control females. The reduced longevity of adult
      females from larval methoprene treatment appeared not to be directly related to
      reduced glycogen, but rather reflected neuroendocrine abnormalities induced by
      this juvenile hormone analogue.

PMID- 1402869
TI  - Photoperiod and the relationship between wing length and body weight in Anopheles
      quadrimaculatus.
AB  - The effect of photoperiod on wing length, body weight, and relationship between
      wing length and body weight was investigated in the mosquito species Anopheles
      quadrimaculatus. Individuals reared under a short photoperiod (8 h light: 16 h
      dark) had longer wings and larger weights than did those reared under a long
      photoperiod (16 h light: 8 h dark). Covariance analysis showed that photoperiod
      and wing length interacted so that photoperiod did not have a uniform effect on
      body weight at all wing lengths. At small mosquito sizes, body weight was higher
      in short than in long-photoperiod individuals of the same wing length, but at
      large mosquito sizes, body weight was higher in long than in short-photoperiod
      individuals of the same wing length. Thus, among smaller mosquitoes of this
      species, wings were disproportionately longer in long-photoperiod individuals,
      but among larger mosquitoes, wings were disproportionately longer in short
      photoperiod individuals. These results, together with previous studies, suggest
      that photoperiod and temperature have similar effects on the developing insect.

PMID- 1402868
TI  - Ecology of Anopheles pulcherrimus in Baluchistan, Iran.
AB  - Studies were conducted on the ecology of Anopheles pulcherrimus over a period of
      20 months in the village of Zeineddini, Sistan and Baluchistan Province,
      southeastern Iran. The species was active throughout the year with 2 peaks of
      activity, April-May and August-September. Light traps captured the highest number
      of An. pulcherrimus females (65%) as compared to cattle bait collections (19.3%),
      pyrethrum space spray catches (14.2%), pit shelter (1%) and human bait
      collections (0.6%). However, 95% of the females captured in light traps were
      unfed or freshly fed females as opposed to about only 44% of those collected in
      pyrethrum space spray catches and pit shelter collections. The species was mainly
      exophilic as shown by the gravid/fed ratio of 0.4 obtained in outlet window
      traps.

PMID- 1402870
TI  - Mosquito vector control and biology in Latin America--a second symposium.
AB  - The second Spanish language symposium presented by the American Mosquito Control
      Association (AMCA) was held as part of the 58th Annual Meeting in Corpus Christi,
      TX in March 1992. The principal objective, as it was for the 1991 symposium, was
      to increase and stimulate greater participation in the AMCA by vector control
      specialists and public health workers from Latin America. This publication
      includes summaries of 25 individual presentations that were given in Spanish. The
      symposium included the following topics: biology and chemical control of Aedes
      aegypti and anopheline vectors of malaria; field and laboratory studies of
      biological control agents for Aedes aegypti; community participation in the
      prevention of dengue; and other various aspects of the biology of other medically
      important arthropods (e.g., Simulium ochraceum, Lutzomyia and Culicoides).

PMID- 1402871
TI  - First record of Aedes albopictus establishment in Italy.
AB  - In September 1991, the first breeding populations of Aedes albopictus were
      discovered in Veneto Region, Italy. Larvae were collected in a wide variety of
      peridomestic containers and in used tires. Attempts were made to eradicate this
      species from infested areas. No larvae or adults of Ae. albopictus were found
      from October 1991 onwards. It is not yet assessed if this was because of the
      control measures taken or due to the low fall temperatures and the short critical
      photoperiod prevailing in the area (L:D, 12:45). Since tire casings are believed
      to be the primary mode of introduction and dispersal of Ae. albopictus, an
      investigation of tire retreading operations was initiated to determine the source
      and mode of introduction of Ae. albopictus into Italy.

PMID- 1402872
TI  - Aedes albopictus and other mosquitoes imported in tires into Durban, South
      Africa.
AB  - The results of surveillance for immature stages of mosquitoes in samples of wet
      tires in 5 consignments imported into Durban from Japan is reported. Three of
      these consignments contained tires with immatures of Aedes aegypti, Ae.
      albopictus and Uranotaenia n. novobscura. The proportions of all the wet tires
      calculated to contain mosquitoes were 189/1,488 (13%), 20/813 (2.5%) and 13/1,032
      (1.3%) which emphasizes the need for effective mosquito control measures to
      prevent Ae. albopictus escaping from such tires and establishing itself in
      Durban.

PMID- 1402873
TI  - Key characters for identifying Aedes bahamensis and Aedes albopictus in North
      America, north of Mexico.
AB  - Aedes bahamensis, a species recently introduced into southern Florida represents
      the first member of the subgenus Howardina to be found in the United States. Its
      separation from all other Nearctic Aedes is the subject of this work, integrating
      it into the North American mosquito keys (Darsie and Ward 1981). The key
      revisions presented are expanded to include the other exotic species now found in
      the United States, Aedes albopictus.

PMID- 1402874
TI  - Edgar A. Smith 1916-1992.

PMID- 1402875
TI  - Chromium picolinate increases membrane fluidity and rate of insulin
      internalization.
AB  - The effects of chromium chloride, chromium nicotinate, and chromium picolinate on
      insulin internalization in cultured rat skeletal muscle cells was examined.
      Insulin internalization was markedly increased in cells cultured in a medium that
      contained chromium picolinate and the increased internalization rate was
      accompanied by a marked increase in the uptake of both glucose and leucine. The
      effect was specific for chromium picolinate since neither zinc picolinate nor any
      of the other forms of chromium tested was effective. The increased insulin
      internalization rate may result from an increase in membrane fluidity since
      chromium picolinate and to a lesser extent, chromium nicotinate, increased the
      membrane fluidity of synthetic liposomal membranes.

PMID- 1402876
TI  - Synthesis, characterization, and antibacterial activity of transition metal
      complexes with 5-hydroxy-7,4'-dimethoxyflavone.
AB  - Complexes of CuII, NiII, CoII, ZnII, FeIII, CrIII, CdII, and MnII with the
      natural product 5-hydroxy-7,4'-dimethoxyflavone have been synthesized and the
      probable structures of these complexes have been proposed on the basis of
      elemental analyses, molecular weight determination, magnetic moments, and
      electronic and IR spectral data. The presence of coordinated and crystal water
      molecules was demonstrated by thermal studies. The antibacterial activity of the
      ligand and all the complexes has been determined on gram positive and gram
      negative bacteria.

PMID- 1402877
TI  - Palladium(II) salt and complexes of spermidine with a six-member chelate ring.
      Synthesis, characterization, and initial DNA-binding and antitumor studies.
AB  - By reaction of spermidine trihydrochloride with K2PdCl4 and PdCl2 at different
      pH's, we have synthesized the [sperH3]2[PdCl4]3 (I), [PdCl2(sperH)]2[PdCl4] (II),
      and [(PdCl2)3(sper)2] (III) compounds. The structure of these compounds was
      studied by IR and 1H NMR; complex II was analyzed by x-ray diffraction. In this
      complex the spermidine is attached to the PdCl2 group forming a six-member
      chelate ring with a protonated terminal amine group. The crystal of
      [PdCl2(sperH)]2[PdCl4] x 2H2O (II) is monoclinic, P2(1)/n, with a = 7.023(1) A, b
      = 12.662(1) A, c = 18.435(3) A, and beta = 99.95(1) degrees, Z = 4, R = 0.051,
      and Rw = 0.058 on the basis of 2690 independent reflections. We have compared the
      antitumor activity in vitro against the isolated human breast carcinoma MDA-MB
      468 cell line of compounds I, II, and III with that of cis
      diamminedichloroplatinum(II), cis-DDP. The results show that compounds III and
      III have values of ID50 similar (0.74 microgram/ml) or even lower (0.56
      microgram/ml) than cis-DDP (0.80 microgram/ml). We also observed that compounds
      I, II, and III have the ability to induce conformational changes in covalently
      closed circular (ccc) form of the pUC8 plasmid DNA. Compounds II and III also
      induce conformational changes in the open circular (oc) form of this plasmid.

PMID- 1402878
TI  - Evidence that the loss of the voltage-dependent Mg2+ block at the N-methyl-D
      aspartate receptor underlies receptor activation during inhibition of neuronal
      metabolism.
AB  - In this study, the importance of the Mg2+ blockade of the N-methyl-D-aspartate
      (NMDA) receptor during metabolic stress was examined in embryonic day 13 chick
      retina. Retina exposed to mild conditions of metabolic stress (i.e., blockade of
      glycolysis with 1 mM iodoacetate for 30 min) underwent acute histological somal
      and neuritic swelling and an increase in gamma-aminobutyric acid (GABA) release
      into the medium. These acute signs of metabolic stress were eliminated by NMDA
      antagonists present during pharmacological blockade of glycolysis, occurred in
      the absence of a net increase in extracellular glutamate or aspartate, and were
      not affected by the presence or absence of Ca2+ in the incubation medium. One
      possible explanation for the activation of NMDA receptors in the absence of an
      increase in extracellular ligand is that NMDA sensitivity during metabolic stress
      may be governed at the receptor level. Depolarization of membrane potential
      during metabolic stress may result in the loss of the Mg2+ blockade from the NMDA
      receptor channel, resulting in an increased potency for glutamate. To test this,
      the dose-response characteristics for NMDA, glutamate, and kainate in the
      presence or absence of extracellular Mg2+ and the effects of Mg2+ on metabolic
      inhibition were examined. The potency for NMDA- or glutamate-mediated acute
      toxicity was enhanced two- to fivefold in the absence of Mg2+. Omission of Mg2+
      greatly decreased the minimal concentration of agonist needed to produce acute
      excitotoxicity; 25 versus 5 microM for NMDA and 300 versus 10 microM for
      glutamate in 1.2 or zero Mg2+, respectively. Elevating external Mg2+ to 20 mM
      completely protected against NMDA-mediated acute toxic effects. In contrast,
      varying external Mg2+ had no effect on kainate-induced toxicity. Acute toxicity
      caused by inhibition of metabolism was not potentiated in the absence of Mg2+ but
      was attenuated by elevating extracellular Mg2+. The protective effect of Mg2+
      during metabolic inhibition was not additive with NMDA antagonists, suggesting
      that the action of Mg2+ was at the level of the NMDA receptor. These findings are
      consistent with the hypothesis that the Mg2+ block is lifted during metabolic
      inhibition and may be the primary event resulting in NMDA receptor activation.

PMID- 1402879
TI  - Correlation between electroencephalogram isoelectric time and hippocampal
      norepinephrine levels, measured by microdialysis, during ischemia in rats.
AB  - It is suggested that norepinephrine (NE) plays a role during transient forebrain
      ischemia. NE may have a protective action against neuronal cell death in the
      hippocampus, or it may be one of the causes of injurious ischemic effects. We
      used the microdialysis technique to study extracellular NE levels in the rat
      hippocampus before, during, and after 30 min of transient incomplete forebrain
      ischemia (induced by four-vessel occlusion) to describe the time course of NE in
      this condition. There was a maximal increase (fivefold) in extracellular NE after
      10 min of reflow only when the electroencephalogram was isoelectric. NE levels
      returned to baseline 40 min after release of the carotid clamps and remained
      constant for the next 80 min. Thus there appears to be a transient NE overflow in
      the hippocampus during ischemia, closely related to the complete loss of brain
      electrical activity.

PMID- 1402880
TI  - Effect of N,N'-dicyclohexylcarbodiimide on acetylcholine release from Torpedo
      synaptosomes and proteoliposomes reconstituted with the proteolipid mediatophore.
AB  - The mediatophore is a presynaptic membrane protein that has been shown to
      translocate acetylcholine (ACh) under calcium stimulation when reconstituted into
      artificial membranes. The mediatophore subunit, a 15-kDa proteolipid, presents a
      very high sequence homology with the N,N'-dicyclohexylcarbodiimide (DCCD)-binding
      proteolipid subunit of the vacuolar-type H(+)-ATPase. This prompted us to study
      the effect of DCCD, a potent blocker of proton translocation, on calcium
      dependent ACh release. The present work shows that DCCD has no effect on ACh
      translocation either from Torpedo synaptosomes or from proteoliposomes
      reconstituted with purified mediatophore. However, using [14C]DCCD, we were able
      to demonstrate that the drug does bind to the 15-kDa proteolipid subunit of the
      mediatophore. These results suggest that although the 15-kDa proteolipid subunits
      of the mediatophore and the vacuolar H(+)-ATPase may be identical, different
      domains of these proteins are involved in proton translocation and calcium
      dependent ACh release and that the two proteins have a different membrane
      organization.

PMID- 1402881
TI  - Lesion-induced changes in the production of newly synthesized and secreted apo-E
      and other molecules are independent of the concomitant recruitment of blood-borne
      macrophages into injured peripheral nerves.
AB  - Peripheral nerve injury produces Wallerian degeneration characterized by a change
      in the composition of resident nonneuronal cells: macrophages are recruited from
      the circulation to join Schwann, fibroblast, and endothelial cells. At the same
      time, the nonneuronal cell population exhibits, as a whole, alterations in
      synthesis and secretion of diffusible molecules, some of which are instrumental
      in nerve repair mechanisms. In this study, we determined whether changes in the
      production of secreted molecules depend on the concomitant modification in cell
      composition. Therefore, we studied the secretion of newly synthesized molecules
      by defined cell populations of intact nerves, intact nerve explants undergoing in
      vitro axonal degeneration, in vivo degenerating nerves, and recruited cells.
      Nerves were incubated in serum-free, [35S]methionine-containing media. Secreted,
      radioactively labeled proteins were precipitated from the medium and analyzed by
      gel electrophoresis. Reduced production of 43-, 46-, and 48-kDa proteins and
      increased production of 33-34-, 37-, 49-, 59-, and 67-kDa proteins were detected
      in in situ degenerating nerves. High-density ultracentrifugation and immunoblot
      analysis revealed that the 33-34-kDa protein is apolipoprotein-E (apo-E). Similar
      alterations in the production of these molecules were detected in intact nerve
      explants from which blood-borne cells were excluded. Apo-E, 37-, 49-, 59-, and 67
      kDa proteins were also produced in frozen nerves that lacked the intact nerve
      nonneuronal cell population. Instead, these preparations contained blood-borne
      cells, primarily macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402882
TI  - Characterization of the irreversible inhibition of high-affinity choline
      transport produced by hemicholinium mustard.
AB  - The inhibition of high-affinity choline transport by hemicholinium mustard (HCM),
      an alkylating analogue of hemicholinium-3, was examined in rat brain synaptosomes
      and guinea pig myenteric plexus. In synaptosomes, 50% high-affinity choline
      transport inhibition occurs with an HCM concentration of 104 nM (4-min
      incubation). A 10-min preincubation with 10 microM HCM results in essentially
      complete (greater than 95%) inactivation that persists after washing. Low
      affinity choline transport in synaptosomes is unaffected by HCM inhibition at all
      concentrations examined (1-50 microM). Time course experiments indicate that the
      maximum irreversible inhibition (58%) seen after a 1-min preincubation with 500
      nM HCM decreases to 46% inhibition after a 15-min preincubation; however,
      analysis of variance reveals that this difference is not significant. HCM
      inhibition of acetylcholine release from myenteric plexus-longitudinal muscle
      preparations persists for at least 2 h after removal of drug from the incubation
      bath; this inactivation can be prevented by coincubation with a high choline
      concentration during treatment with the mustard. In contrast, inhibition produced
      by the parent compound hemicholinium-3 is largely reversed by washing in both
      preparations examined. The observed potency and selectivity of HCM suggest its
      usefulness as a covalent probe for high-affinity choline transport.

PMID- 1402883
TI  - Beta-amyloid precursor protein isoforms in various rat brain regions and during
      brain development.
AB  - To address the question of the possible functions of different Alzheimer's
      disease beta-amyloid precursor protein (beta-APP) isoforms in the brain, we
      studied their expression at different times during postnatal rat brain
      development and in various regions of the adult rat brain. Polyclonal antibodies
      directed to two peptide antigens were used. The majority of all beta-APP forms
      was found to be soluble as revealed by western blot analysis. The highest level
      of most beta-APP forms was reached in the second postnatal week, which is the
      time of brain maturation and completion of synaptic connections. Strikingly high
      concentrations of the Kunitz protease inhibitor-containing beta-APP were present
      in the adult olfactory bulb, where continuous synaptogenesis occurs in the adult
      animal. These findings support the idea of an involvement of beta-APPs in the
      processes of cell differentiation and, probably, in the establishment of synaptic
      contacts.

PMID- 1402884
TI  - The binding properties of the particulate and solubilized sulfonylurea receptor
      from cerebral cortex are modulated by the Mg2+ complex of ATP.
AB  - Glibenclamide closes an ATP-sensitive K+ channel (K-ATP channel) by interaction
      with the sulfonylurea receptor in the plasma membrane of pancreatic B cells and
      thereby initiates insulin release. Previous studies demonstrated that the Mg2+
      complex of ATP decreases glibenclamide binding to the sulfonylurea receptor from
      pancreatic islets. The aim of the present study was to examine the effect of
      adenine and guanine nucleotides on binding of sulfonyl-ureas to the cerebral
      sulfonylurea receptor. For this purpose, binding properties of the particulate
      and solubilized site from rat or pig cerebral cortex were analyzed. Maximum
      recovery of receptors in detergent extracts amounted to 40-50%. Specific binding
      of [3H]glibenclamide to the solubilized receptors corresponded well to specific
      binding to microsomes. In microsomes and detergent extracts, the Mg2+ complexes
      of ATP, ADP, GTP, and GDP inhibited binding of [3H]glibenclamide. These effects
      were not observed in the absence of Mg2+. In detergent extracts, Mg-ATP (300
      microM) reduced the number of high-affinity sites for [3H]-glibenclamide by 52%
      and increased the dissociation constant for [3H]glibenclamide by eightfold; Mg
      ATP was half-maximally effective at 41 microM. Alkaline phosphatase accelerated
      the reversal of Mg-ATP-induced inhibition of [3H]glibenclamide binding. The data
      suggest similar control of the sulfonylurea receptor from brain and pancreatic
      islets by protein phosphorylation.

PMID- 1402885
TI  - Evidence for a new member of the myosin I family from mammalian brain.
AB  - Myosin I is an actin-based motor responsible for powering a wide variety of
      motile activities in amebae and slime molds and has been found previously in
      vertebrates as the lateral bridges within intestinal epithelial cell microvilli.
      Although neurons exhibit extensive cellular and intracellular motility, including
      the production of ameboid-like growth cones during development, the proteins
      responsible for the motor in these processes are unknown. Here, we report the
      isolation of a partially purified protein fraction from bovine brain that is
      enriched for a 150-kDa protein; immunochemical and biochemical analyses suggest
      that this protein possesses a number of functional properties that have been
      ascribed to myosin I from various sources. These properties include an elevated
      K(+)-EDTA ATPase, a modest actin-activated Mg(2+)-ATPase, the ability to bind
      calmodulin, and a ready association with phospholipid vesicles made from
      phosphatidylserine, but not from phosphatidylcholine. The combination of these
      properties, together with a molecular mass of 150 kDa (most myosin I molecules
      found to date have molecular masses in the range 110-130 kDa) yet recognition by
      an anti-myosin I antibody, suggests the presence of a new member of the myosin I
      family within mammalian brain.

PMID- 1402886
TI  - Nuclear magnetic resonance studies on the effects of decreased external sodium on
      guinea pig cerebral cortex slices and the permeabilities of various sodium
      substitutes.
AB  - Decreasing the external sodium concentration ([Na+]e) to 10 mM in the presence of
      280 mM sucrose had no significant effect on phosphocreatine (PCr) or on
      intracellular pH (pHi) as assessed using 31P nuclear magnetic resonance
      spectroscopy. Zero [Na+]e in the presence of 300 mM sucrose caused a fall in PCr
      levels to 50% of control values, and the pHi fell to 6.85 from a control value of
      7.30. 1H nuclear magnetic resonance spectroscopy confirmed that the sucrose had
      not entered the tissue. The decreases in PCr content and in pHi, known to occur
      on depolarization using 40 mM external potassium concentration ([K+]e), were
      further decreased in the presence of 10 mM [Na+]e), to 51.4 +/- 4.0 and 6.80 +/-
      0.10% of control values, respectively. The free intracellular magnesium
      concentration was significantly increased from a control value of 0.37 +/- 0.10
      mM to 0.66 +/- 0.13 mM (p less than 0.001), when [Na+]e was decreased to 10 mM,
      but was not further affected by high [K+]e or zero Na+. Membrane permeabilities
      of the sodium substitutes N-methyl-D-glucamine (NMG),
      tris(hydroxymethyl)aminomethane (Tris), tetramethylammonium (TMA), and choline
      were assessed using 1H nuclear magnetic resonance spectroscopy. In the presence
      of 10 mM [Na+]e, NMG, TMA, and choline (all at 140 mM) were taken up and remained
      within the tissue for at least 2 h, but no uptake of Tris (140 mM) or sucrose
      (above) could be detected. Tissue lactate levels (from the lactate/N-acetyl
      aspartate ratio) increased in the presence of the substitutes that were taken up,
      although no change in pH was detected.

PMID- 1402887
TI  - Stimulus deprivation increases pineal Gs alpha and G beta.
AB  - Denervation and other forms of stimulus deprivation cause an increase in the
      magnitude of subsequent responses, a phenomenon commonly referred to as
      denervation supersensitivity. This has been well demonstrated with the cyclic AMP
      response to norepinephrine in the pineal gland. In the present report, we address
      the question of whether stimulus deprivation alters alpha and beta subunits of
      the GTP binding regulatory protein that stimulates adenylyl cyclase activity
      (Gs). Stimulus deprivation of the pineal gland was produced by denervation
      (superior cervical ganglionectomy), decentralization of the superior cervical
      ganglia, or by exposure of the animal to continuous lighting. All increased both
      the alpha and beta subunits of Gs (Gs alpha and G beta) by up to fourfold, as
      estimated using semiquantitative western blot technology. These effects were
      detectable after 1 day of stimulus deprivation and were sustained for 2 weeks.
      The stimulatory effects of constant light-induced stimulus deprivation were also
      apparent by measuring cholera toxin-dependent ADP-ribosylation of Gs alpha, which
      revealed a four-fold increase in the amount of labeled substrate. The results of
      in vivo studies were confirmed with in vitro studies, which demonstrated a
      spontaneous increase in both Gs alpha and G beta during 72 h of organ culture.
      The constant light-induced increases in both Gs alpha and G beta were prevented
      by continuous administration of isoproterenol (0.3 mg/kg/day), supporting the
      suggestion that adrenergic stimulation controls the levels of Gs alpha and G
      beta. These studies indicate that stimulus deprivation increases both Gs alpha
      and G beta.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402889
TI  - Regional and subcellular localization of Li+ and other cations in the rat brain
      following long-term lithium administration.
AB  - Rats were given LiCl in their diet (40 mmol/kg dry weight) for at least 3 months
      to elucidate the regional and subcellular localization of Li+ in the brain as
      well as the effect of chronic lithium administration on the distribution of other
      cations. At steady-state the mean concentrations of Li+ were 0.66 mmol/kg wet
      weight in the whole brain and 0.52 mM in plasma. The tissue/plasma concentration
      ratio exceeded unity in all anatomical regions. No region showed excessive
      accumulation of Li+. Whole brain or regional contents of Na+ or K+ were
      unaffected by lithium treatment. Subcellular Li+ localization was demonstrated in
      nuclear, crude mitochondrial, and microsomal fractions of whole brain homogenate.
      Subfractionation of the crude mitochondrial fraction revealed energy-independent
      intrasynaptosomal and intramitochondrial Li+ and K+ localization at 0-4 degrees
      C. Li+ administered in vivo disappeared within 10 min from synaptosomes incubated
      at 37 degrees C. Li+ added in vitro at 1 mM attained a synaptosomal steady-state
      concentration within 30 min at 37 degrees C. In control rats, synaptosomal
      concentrations and synaptosomal/medium concentration gradients of cations
      paralleled their respective in vivo concentrations and gradients. Lithium
      treatment caused synaptosomal depletion of K+ and Mg2+ and hence probably partial
      membrane depolarization. Addition of 1 mM Li+ in vitro also caused synaptosomal
      Mg2+ depletion. The results indicate that Li+ is "accumulated" in brain sediments
      and synaptosomes following its long-term treatment. The estimated intracellular
      and intrasynaptosomal Li+ concentrations are lower than predicted by passive
      distribution according to the Nernst equation, evidencing active extrusion of
      Li+.

PMID- 1402888
TI  - Heterogeneity of [3H]dipyridamole binding to CNS membranes: correlation with
      [3H]nitrobenzylthioinosine binding and [3H]uridine influx studies.
AB  - The relationship between the nucleoside transport system and the
      nitrobenzylthioinosine-sensitive and -resistant [3H]dipyridamole binding sites
      was examined by comparing the characteristics of [3H]dipyridamole binding with
      those of [3H]nitrobenzylthioinosine binding and [3H]-uridine influx in rabbit and
      guinea pig cerebral cortical synaptosomes. Two distinct high-affinity
      synaptosomal membrane-associated [3H]dipyridamole binding sites, with different
      sensitivities to inhibition by nitrobenzylthioinosine, were characterized in the
      presence of 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS,
      0.01%) to prevent [3H]dipyridamole binding to glass tubes and filters. The
      nitrobenzylthioinosine-resistant [3H]-dipyridamole binding sites represented a
      greater proportion of the total membrane sites in guinea pig than in rabbit (40
      vs. 10% based on inhibition studies). In rabbit, nitrobenzylthioinosine-sensitive
      [3H]dipyridamole binding (KD = 1.4 +/- 0.2 nM) and [3H]nitrobenzylthioinosine
      binding (KD = 0.30 +/- 0.01 nM) appeared to involve the same membrane site
      associated with the nitrobenzylthioinosine-sensitive nucleoside transporter. By
      mass law analysis, [3H]-dipyridamole binding in guinea pig could be resolved into
      two components based on sensitivity to inhibition by 1 microM
      nitrobenzylthioinosine. The nitrobenzylthioinosine-resistant [3H]dipyridamole
      binding sites were relatively insensitive to inhibition by all of the nucleoside
      transport substrates and inhibitors tested, with the exception of dipyridamole
      itself. In guinea pig synaptosomes, 100 microM dilazep blocked
      nitrobenzylthioinosine-resistant [3H]uridine transport completely but inhibited
      the nitrobenzylthioinosine-resistant [3H]dipyridamole binding component by only
      20%. Furthermore, a greater percentage of the [3H]dipyridamole binding was
      nitrobenzylthioinosine resistant in guinea pig compared with rabbit, yet both
      species had a similar percentage of nitrobenzylthioinosine-resistant [3H]uridine
      transport.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402890
TI  - The adenosine analogue N6-L-phenylisopropyladenosine inhibits catecholamine
      secretion from bovine adrenal medulla cells by inhibiting calcium influx.
AB  - We reported earlier that adenine nucleotides and adenosine inhibit acetylcholine
      induced catecholamine secretion from bovine adrenal medulla chromaffin cells. In
      this article, we used an adenosine analogue, N6-L-phenylisopropyladenosine (PIA),
      to study the mechanism underlying inhibition of catecholamine secretion by
      adenosine. PIA inhibits secretion induced by a nicotinic agonist, 1,1-dimethyl-4
      phenylpiperazinium, or by elevated external K+. The half-maximal effect on 1,1
      dimethyl-4-phenylpiperazinium-induced secretion occurred at approximately 5 x 10(
      5) M. The inhibition is immediate and reversible. Fura-2 measurements of
      cytosolic free Ca2+ indicate that PIA inhibits Ca2+ elevation caused by
      stimulation; measurements of 45Ca2+ influx show that PIA inhibits uptake of Ca2+.
      PIA does not inhibit calcium-evoked secretion from digitonin-permeabilized cells,
      nor does PIA cause any significant change in the dependence of catecholamine
      secretion on calcium concentration. These data suggest that inhibition by PIA
      occurs at the level of the voltage-sensitive calcium channel.

PMID- 1402891
TI  - m-Sulfonate benzene diazonium chloride: a powerful affinity label for the gamma
      aminobutyric acid binding site from rat brain.
AB  - m-Sulfonate benzene diazonium chloride (MSBD) was used to affinity-label the
      gamma-aminobutyric acid (GABA) binding site from rat brain membranes. To assess
      the irreversibility of the labeling reaction, we used an efficient ligand
      dissociation procedure combined to a rapid [3H]muscimol binding assay, both steps
      being performed on filter-adsorbed membranes. Inactivation of specific [3H]
      muscimol binding sites by MSBD and its prevention by GABA were both time- and
      concentration-dependent. The time course of MSBD labeling was shortened as the pH
      of the incubation medium was increased from 6.2 to 8. These data suggest that
      MSBD can efficiently label the GABA binding site through alkylation of a residue
      having an apparent dissociation constant around neutrality.

PMID- 1402892
TI  - Effects of vasopressin on blood-brain transfer of methionine in dogs.
AB  - We used a simplified probe detection system for positron-emitting radionuclides
      in order to measure blood-brain barrier transport of amino acids in anesthetized
      dogs. Plasma and brain time-activity curves were recorded after intravenous bolus
      injection of L-[11C]methionine before and after administration of 1 microgram of
      vasopressin. Three-compartment models with three or four transfer coefficients
      were used to derive the kinetics of L-[11C]methionine uptake in brain. The blood
      brain clearance of the tracer (K1) was 0.075 ml ml-1 min-1 before and 0.041 ml ml
      1 min-1 after injection of vasopressin. The partition volume and the initial
      distribution (plasma) volume of methionine were unchanged and within the expected
      limits. The net accumulation rate of methionine (K), estimated by both the four
      parameter (kinetic) and three-parameter (graphic) approaches, decreased after
      vasopressin injection in all six studies.

PMID- 1402893
TI  - Comparison of rates of local cerebral glucose utilization determined with deoxy[1
      14C]glucose and deoxy[6-14C]glucose.
AB  - The activity of the pentose phosphate shunt pathway in brain is thought to be
      linked to neurotransmitter metabolism, glutathione reduction, and synthetic
      pathways requiring NADPH. There is currently no method available to assess flux
      of glucose through the pentose phosphate pathway in localized regions of the
      brain of conscious animals in vivo. Because metabolites of deoxy[1-14C]glucose
      are lost from brain when the experimental period of the deoxy[14C]glucose method
      exceeds 45 min, the possibility was considered that the loss reflected activity
      of this shunt pathway and that this hexose might be used to assay regional
      pentose phosphate shunt pathway activity in brain. Decarboxylation of deoxy[1
      14C]glucose by brain extracts was detected in vitro, and small quantities of 14C
      were recovered in the 6-phosphodeoxygluconate fraction when deoxy[14C]glucose
      metabolites were isolated from freeze-blown brains and separated by HPLC. Local
      rates of glucose utilization determined with deoxy[1-14C]glucose and deoxy[6
      14C]glucose were, however, similar in 20 brain structures at 45, 60, 90, and 120
      min after the pulse, indicating that the rate of loss of 14CO2 from deoxy[1
      14C]glucose-6-phosphate in normal adult rat brain is too low to permit assay
      pentose phosphate shunt activity in vivo. Further metabolism of deoxy[1
      14]glucose-6-phosphate via this pathway does not interfere during routine use of
      the deoxyglucose method or explain the progressive decrease in calculated
      metabolic rate when the experimental period exceeds 45 min.

PMID- 1402894
TI  - Brain protein synthesis in the conscious rat using L-[35S]methionine:
      relationship of methionine specific activity between plasma and precursor
      compartment and evaluation of methionine metabolic pathways.
AB  - The method previously developed for the measurement of rates of methionine
      incorporation into brain proteins assumed that methionine derived from protein
      degradation did not recycle into the precursor pool for protein synthesis and
      that the metabolism of methionine via the transmethylation pathway was
      negligible. To evaluate the degree of recycling, we have compared, under steady
      state conditions, the specific activity of L-[35S] methionine in the tRNA-bound
      pool to that of plasma. The relative contribution of methionine from protein
      degradation to the precursor pool was 26%. Under the same conditions, the
      relative rate of methionine flux into the transmethylation cycle was estimated to
      be 10% of the rate of methionine incorporation into brain proteins. These results
      indicate the following: (a) there is significant recycling of unlabeled
      methionine derived from protein degradation in brain; and (b) the metabolism of
      methionine is directed mainly towards protein synthesis. At normal plasma amino
      acid levels, methionine is the amino acid which, to date, presents the lowest
      degree of dilution in the precursor pool for protein synthesis. L-[35S]
      Methionine, therefore, presents radiobiochemical properties required to measure,
      with minimal underestimation, rates of brain protein synthesis in vivo.

PMID- 1402895
TI  - Accumulation of lysosphingolipids in tissues from patients with GM1 and GM2
      gangliosidoses.
AB  - By using a sensitive method, we assayed lysocompounds of gangliosides and
      asialogangliosides in tissues from four patients with GM2 gangliosidosis (one
      with Sandhoff disease and three with Tay-Sachs disease) and from three patients
      with GM1 gangliosidosis [one with infantile type (fetus), one with late
      infantile, and one with adult type]. In the brain and spinal cord of all the
      patients except for an adult GM1 gangliosidosis patient, abnormal accumulation of
      the lipids was observed, though the concentration in the fetal tissue was low. In
      GM2 gangliosidosis, the amounts of lyso GM2 ganglioside accumulated in the brain
      were similar among the patient with Sandhoff disease and the patients with Tay
      Sachs disease, whereas the concentration of asialo lyso GM2 ganglioside in the
      brain was higher in the former patient than in the latter patients. By comparing
      the sphingoid bases of neutral sphingolipids, gangliosides, and
      lysosphingolipids, it was suggested that lysosphingolipids in the diseased tissue
      are synthesized by sequential glycosylation from free sphingoid bases, but not by
      deacylation of the sphingolipids. Because lysosphingolipids are known to be
      cytotoxic, the abnormally accumulated lysophingolipids may well be the
      pathogenetic agent for the neuronal degeneration in gangliosidoses.

PMID- 1402896
TI  - Alterations in extracellular and tissue levels of biogenic amines in rat brain
      induced by the serotonin2 receptor antagonist, ritanserin.
AB  - Systemic administration of ritanserin elicited rapid changes in dopamine (DA) and
      serotonin (5-HT) levels in both dialysate and neuronal tissue extracts. These
      effects occurred in both a site-selective and a dose-related manner. Increases in
      extracellular levels of DA and 5-HT in the nucleus accumbens were maximal at 120
      140 min after treatment. A dose of 0.63 mg/kg of ritanserin elicited larger and
      more prolonged increases in extracellular DA and 5-HT levels than did the 0.3
      mg/kg dose. By contrast, 0.63 mg/kg of ritanserin elicited no changes in either
      DA or 5-HT levels with dialysate collected from the striatum. Ritanserin also
      induced dose-related decreases in tissue levels of DA and 5-HT from the nucleus
      accumbens. The site specificity of action was again noted in that there were no
      dose-dependent decreases in tissue levels of DA or 5-HT measured from the
      striatum. Ritanserin exerted little effect on metabolite levels from either
      dialysate or tissue extracts. Taken together, these findings show that selective
      5-HT2 receptor antagonism modulates DA and 5-HT neurotransmission in a specific
      manner. These actions appear to involve increased release of DA and 5-HT rather
      than significant changes in metabolism. These findings add further weight to the
      importance of 5-HT2 receptor interactions as an important component of
      antipsychotic activity.

PMID- 1402897
TI  - Phorbol ester-mediated stimulation of phospholipase D activity in sciatic nerve
      from normal and diabetic rats.
AB  - Evidence for the presence of phospholipase D activity in sciatic nerve was
      obtained by incubation of 32P-prelabeled nerve segments in the presence of
      ethanol and measurement of [32P]phosphatidylethanol (PEth) formation expressed as
      a fraction of total phospholipid radioactivity. PEth synthesis was enhanced with
      increasing concentrations of ethanol (100 mM-2 M). 4-beta-Phorbol dibutyrate (100
      nM-1 microM) stimulated PEth formation up to twofold in a time- and dose
      dependent manner. The stimulatory effect evoked by 100 nM phorbol ester was
      completely abolished by Ro 31-8220 (compound 3), a selective protein kinase C
      inhibitor. Efforts to identify the phospholipid precursor of PEth were
      unsuccessful, suggesting this product arises from a small discrete precursor
      pool. On subcellular fractionation of nerve, the ratio of basal and 4-beta
      phorbol dibutyrate-stimulated phospholipase D activity recovered in a myelin
      enriched fraction, compared with a nonmyelin fraction, was 0.5 when results are
      expressed as a percentage of total phospholipid radioactivity. This ratio rises
      to 1.2 if the results are calculated assuming only phosphatidylcholine and
      phosphatidylethanolamine are potential precursors. The results suggest that
      myelin is a major locus of phospholipase D activity. Nerve from streptozotocin
      induced diabetic and control animals displayed the same basal phospholipase D
      activity, but the enzyme in diabetic nerve was stimulated to a greater extent by
      a suboptimal concentration of 4-beta-phorbol dibutyrate. These results support
      the conclusion that protein kinase C modulates phospholipase D activity in nerve
      and suggest that in diabetic nerve the enzyme activation mechanism may possess
      increased sensitivity.

PMID- 1402898
TI  - Bradykinin and phorbol dibutyrate activate phospholipase D in PC12 cells by
      different mechanisms.
AB  - Bradykinin is known to activate phospholipase D in PC12 cells. Because bradykinin
      may also activate protein kinase C in these cells, the possible role of this
      kinase in mediating the action of bradykinin was investigated. Phospholipase D
      activity in PC12 cells was assayed by measuring the formation of
      [3H]phosphatidylethanol in cells prelabeled with [3H]palmitic acid and incubated
      in the presence of ethanol. The phorbol ester phorbol dibutyrate mimicked the
      effect of bradykinin on [3H]phosphatidylethanol formation. The protein kinase C
      inhibitor staurosporine (1 microM) significantly attenuated the effect of phorbol
      dibutyrate (35-70%) but did not block bradykinin-stimulated
      [3H]phosphatidylethanol formation. In addition, the effect of phorbol dibutyrate
      was additive with that of bradykinin. Prolonged treatment of PC12 cells with
      phorbol dibutyrate (24 h), which depletes cells of protein kinase C, greatly
      attenuated bradykinin-stimulated [3H]phosphatidylethanol accumulation in intact
      cells. This treatment caused a 55% decrease in both fluoride-stimulated
      [3H]phosphatidylethanol production in the intact cell and phospholipase D
      activity as assessed by an in vitro assay using an exogenous substrate.
      Therefore, the effect of prolonged phorbol dibutyrate pretreatment on bradykinin
      stimulated [3H]phosphatidylethanol production could not be attributed exclusively
      to the depletion of protein kinase C. Thus, although the data with phorbol ester
      suggest that activation of protein kinase C leads to an increase in phospholipase
      D activity, this kinase probably does not play a role in mediating the effect of
      bradykinin. Finally, although pretreatment with phorbol dibutyrate completely
      blocked bradykinin-stimulated [3H]phosphatidylethanol production in the intact
      cell, it only partially (approximately 50%) inhibited bradykinin-stimulated
      [3H]diacylglycerol formation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402899
TI  - gamma-Aminobutyric acid and glycine modulate each other's release through
      heterocarriers sited on the releasing axon terminals of rat CNS.
AB  - The ability of gamma-aminobutyric acid (GABA) and glycine (Gly) to modulate each
      other's release was studied in synaptosomes from rat spinal cord, cerebellum,
      cerebral cortex, or hippocampus, prelabeled with [3H]GABA or [3H]Gly and exposed
      in superfusion to Gly or to GABA, respectively. GABA increased the spontaneous
      outflow of [3H]Gly (EC50, 20.8 microM) from spinal cord synaptosomes. Neither
      muscimol nor (-)-baclofen, up to 300 microM, mimicked the effect of GABA, which
      was not antagonized by either bicuculline or picrotoxin. However, the effect of
      GABA was counteracted by the GABA uptake inhibitors nipecotic acid and N-(4,4
      diphenyl-3-butenyl)nipecotic acid. Moreover, the GABA-induced [3H]Gly release was
      Na+ dependent and disappeared when the medium contained 23 mM Na+. The effect of
      GABA was Ca2+ independent and tetrodotoxin insensitive. Conversely, Gly enhanced
      the outflow of [3H]GABA from rat spinal cord synaptosomes (EC50, 100.9 microM).
      This effect was insensitive to both strychnine and 7-chlorokynurenic acid,
      antagonists at Gly receptors, but it was strongly Na+ dependent. Also, the Gly
      evoked [3H]GABA release was Ca2+ independent and tetrodotoxin insensitive. GABA
      increased the outflow of [3H]Gly (EC50, 11.1 microM) from cerebellar
      synaptosomes; the effect was not mimicked by either muscimol or (-)-baclofen nor
      was it prevented by bicuculline or picrotoxin. The GABA effect was, however,
      blocked by GABA uptake inhibitors and was Na+ dependent. Gly increased [3H]GABA
      release from cerebellar synaptosomes (EC50, 110.7 microM) in a strychnine- and 7
      chlorokynurenic acid-insensitive manner. This effect was Na+ dependent. The
      effects of GABA on [3H]Gly release seen in spinal cord and cerebellum could be
      reproduced also with cerebrocortical synaptosomes.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1402900
TI  - Human brain beta A4 amyloid protein precursor of Alzheimer's disease:
      purification and partial characterization.
AB  - The major component of the amyloid deposition that characterizes Alzheimer's
      disease is the 4-kDa beta A4 protein, which is derived from a much larger amyloid
      protein precursor (APP). A procedure for the complete purification of APP from
      human brain is described. The same amino terminal sequence of APP was found in
      two patients with Alzheimer's disease and one control subject. Two major forms of
      APP were identified in human brain with apparent molecular masses of 100-110 kDa
      and 120-130 kDa. Soluble and membrane fractions of brain contained nearly equal
      amounts of APP in both humans and rats. Immunoprecipitation with carboxyl
      terminus-directed antibodies indicates that the soluble forms of APP are
      truncated. Carboxyl terminus truncation of membrane-associated forms of human
      brain APP was also found to occur during postmortem autolysis. The availability
      of purified human brain APP will facilitate the investigation of its normal
      function and the events that lead to its abnormal cleavage in patients with
      Alzheimer's disease.

PMID- 1402902
TI  - Effects of sulfate ions on Alzheimer beta/A4 peptide assemblies: implications for
      amyloid fibril-proteoglycan interactions.
AB  - To model the possible involvement of sulfated proteoglycans in amyloidogenesis,
      we examined the influence of sulfate ions, heparan, and Congo red on the
      conformation and morphology of peptides derived from the Alzheimer beta/A4
      amyloid protein. The peptides included residues 11-28, 13-28, 15-28, and 11-25 of
      beta/A4. Negative-stain electron microscopy revealed a sulfate-specific tendency
      of the preformed peptide fibrillar assemblies of beta(11-28), beta(13-28), and
      beta(11-25), but not beta(15-28), to undergo extensive lateral aggregation and
      axial growth into "macrofibers" that were approximately 0.1-0.2 micron wide by
      approximately 20-30 microns long. Such effects were observed at low sulfate
      concentrations (e.g., 5-50 mM) and could not be reproduced under comparable
      conditions with Na2HPO4, Na2SeO4, or NaCl. Macrofibers in NaCl were only observed
      at 1,000 mM. At physiological ionic strength of NaCl, fibril aggregation was
      observed only with addition of sulfate ions at 5-50 mM. Selenate ions, by
      contrast with sulfate ions, induced only axial and not substantial lateral
      aggregation of fibrils. X-ray diffraction indicated that the original cross-beta
      peptide conformation remained unchanged; however, sulfate binding did produce an
      intense approximately 65 A meridional reflection not recorded with control
      peptides. This new reflection probably arises from the periodic deposition of the
      electron-dense sulfate along the (long) axis of the fibril. The sulfate binding
      could provide sites for the binding of additional fibrils that generate the
      observed lateral and axial aggregation. The binding of heparan to beta(11-28)
      also produced extensive aggregation, suggesting that in vivo sulfated compounds
      can promote macrofibers. The amyloid-specific, sulfonated dye Congo red, even in
      the presence of sulfate ions, produced limited aggregation and reduced axial
      growth of the fibrils. Therefore, electrostatic interactions are important in the
      binding of exogenous compounds to amyloid fibrils. Our findings suggest that the
      sulfate moieties of certain molecules, such as glycosaminoglycans, may affect the
      aggregation and deposition of amyloid fibrils that are observed as extensive
      deposits in senile plaques and cerebrovascular amyloid.

PMID- 1402901
TI  - Melatonin increases serotonin N-acetyltransferase activity and decreases dopamine
      synthesis in light-exposed chick retina: in vivo evidence supporting melatonin
      dopamine interaction in retina.
AB  - The administration of melatonin, either peripherally (0.01-10 mg/kg) or
      intraocularly (0.001-10 mumol/eye), to light-exposed chicks dose-dependently
      increased serotonin N-acetyltransferase (NAT) activity in retina but not in
      pineal gland. The effect of melatonin was slightly but significantly reduced by
      luzindole (2-benzyl-N-acetyltryptamine), and not affected by two other purported
      melatonin antagonists, N-acetyltryptamine and N-(2,4-dinitrophenyl)-5
      methoxytryptamine (ML-23). The elevation of the enzyme activity induced by
      melatonin was substantially stronger than that evoked by 5-hydroxytryptamine, N
      acetyl-5-hydroxytryptamine, or 5-methoxytryptamine. The melatonin-evoked rise in
      the retinal NAT activity was counteracted by two dopamine D2 receptor agonists,
      quinpirole and apomorphine, and prevented by the dopamine D2 receptor blocker
      spiroperidol, and by an inhibitor of dopamine synthesis, alpha-methyl-p-tyrosine.
      Melatonin (0.1-10 mg/kg i.p.) dose-dependently decreased the levels of dopamine
      and 3,4-dihydroxyphenylacetic acid (DOPAC), as well as the DOPAC/dopamine ratio,
      in chick retina but not in forebrain. The results obtained (1) indicate that
      melatonin in vivo potently inhibits dopamine synthesis selectively in retina, and
      (2) suggest that the increase in retinal NAT activity evoked by melatonin in
      light-exposed chicks is an indirect action of the compound, and results from the
      disinhibition of the NAT induction process from the dopaminergic (inhibitory)
      signal. The results provide in vivo evidence supporting the idea (derived on the
      basis of in vitro findings) that a mutually antagonistic interaction between
      melatonin and dopamine operates in retinas of living animals.

PMID- 1402903
TI  - Monoclonal antibody analysis of phosphatidylserine and protein kinase C
      localizations in developing rat cerebellum.
AB  - Understanding the topographical relationships between phosphatidylserine (PS) and
      protein kinase C (PKC) within neurons can provide clues about the mechanism of
      translocation and activation of PKC. For this purpose we applied monoclonal
      antibodies (Abs) of PS and PKC to sections of developing rat cerebellum. The anti
      PKC Ab immunohistochemical pattern showed homogeneous staining of Purkinje cells
      over various postnatal ages, whereas the anti-PS Ab staining showed a
      heterogeneous localization over these ages. Purkinje cells did not stain well
      between postnatal day 14 (PND 14) and PND 21, suggesting that the PS was lost
      from the membrane during preparation of the sections during this period. These
      data imply that interactions between PS and PKC vary in Purkinje cells during
      postnatal development.

PMID- 1402904
TI  - Endogenous dopamine facilitates striatal in vivo acetylcholine release by acting
      on D1 receptors localized in the striatum.
AB  - Intrastriatal application of the D1 antagonist SCH 23390 by two procedures,
      reverse dialysis (20 microM) and local injection (0.45 nmol per striatum),
      elicited a reduction in acetylcholine (ACh) release superimposable on that
      induced by systemic administration. The novel selective D1 antagonist SCH 39166
      produced a similar decreasing effect on striatal ACh release on local injection
      (0.45 nmol per striatum). On the other hand, local application of SCH 23390 into
      the frontal cortices (0.45 nmol per side) failed to alter striatal ACh overflow,
      indicating that the drug does not diffuse out of its injection site to any
      significant extent. The dopamine release inducer d-amphetamine (2 mg/kg s.c.) and
      the dopamine uptake inhibitor cocaine raised ACh release like the D1 agonists.
      These effects were completely blocked by 10 microM SCH 23390 applied by reverse
      dialysis. The results suggest that D1 receptors regulating ACh release are
      located in the striatum.

PMID- 1402905
TI  - Pathological phosphorylation causes neuronal death: effect of okadaic acid in
      primary culture of cerebellar granule cells.
AB  - We have investigated the role of protracted phosphatase inhibition and the
      consecutive protracted protein phosphorylation on neuronal viability. We found
      that in primary cultures of cerebellar granule neurons, the protracted (24-h)
      inhibition of the serine/threonine protein phosphatases 1 and 2A (EC 3.1.3.16) by
      treatment of the cultures with okadaic acid (OKA; 5-20 nM) caused neurotoxicity
      that could be inhibited by the protein kinase inhibitor 1-(5
      isoquinolinylsulfonyl)-2-methylpiperazine (H7) or by the previous down-regulation
      of the neuronal protein kinase C (PKC; ATP:protein phosphotransferase; EC
      2.7.1.37). PKC was down-regulated by exposure of the cultures for 24 h to 100 nM
      phorbol 12-myristate 13-acetate (TPA). The effect of the drugs used in the
      viability studies on the pattern of protein phosphorylation was measured by
      quantitative autoradiography. In particular, the 50- and 80-kDa protein bands
      showed dramatic changes in the degree of phosphorylation: increase by OKA and
      brief TPA treatment; decrease by H7 or 24 h of TPA treatment; and inhibition of
      the OKA-induced increase by H7 or 24 h of TPA treatment. The results suggest that
      the protracted phosphorylation, in particular that mediated by PKC, may lead to
      neuronal death and are in line with our previous suggestion that prolonged PKC
      translocation is operative in glutamate neurotoxicity.

PMID- 1402906
TI  - Intraventricular infusions of anti-neural cell adhesion molecules in a discrete
      posttraining period impair consolidation of a passive avoidance response in the
      rat.
AB  - Intraventricular infusions of anti-neural cell adhesion molecule (anti-NCAM) are
      demonstrated to inhibit consolidation of a passive avoidance response when
      administered in the 6-8 h posttraining period. Anti-NCAM was ineffective when
      administered during training or at any other time up to 10 h thereafter, and no
      amnesic effects were observed with absorbed anti-NCAM or anti-neurofilament
      protein. Amnesia was observed only at the 48-h recall time, and this could not be
      attributed to poor antibody penetration or a prolonged residence time, as studies
      with 125I-labelled anti-NCAM in trained animals demonstrated a rapid accumulation
      into all brain regions, and this was marked in the olfactory bulb and
      hippocampus, areas showing an inherent and paradigm-specific increase in NCAM
      sialylation state, respectively. The lack of an amnesic action at the 24-h recall
      time is attributed to anti-NCAM-impaired synapse structuring becoming apparent
      following the paradigm-specific increases in NCAM sialylation state.

PMID- 1402907
TI  - Time-dependent inhibition of stimulated adrenal catecholamine release by
      staurosporine.
AB  - Staurosporine, a potent inhibitor of protein kinases, is used to study the
      involvement of protein kinases in cellular processes. In the present studies, the
      effect of prolonged staurosporine treatment on catecholamine secretion in
      cultured bovine adrenal chromaffin cells was examined. Staurosporine inhibits
      catecholamine release stimulated by 10 microM nicotine, depolarizing
      concentrations of potassium (56 mM KCl), and 2 mM BaCl2. The effects of
      staurosporine on KCl-stimulated release are time dependent, with a half-time of
      approximately 50 min and a maximal inhibition at 2 h. Our results indicate that
      activation of a staurosporine-sensitive protein kinase is not directly involved
      in the stimulus-secretion coupling process. This does not rule out the
      possibility that Ca2+/phospholipid-dependent protein kinase or other protein
      kinases may acutely modulate release. However, these results suggest that a
      protein(s), which is phosphorylated by a staurosporine-sensitive protein
      kinase(s), is required to maintain the integrity of the stimulus-secretion
      coupling process.

PMID- 1402908
TI  - Reactive oxygen species and the central nervous system.
AB  - Radicals are species containing one or more unpaired electrons, such as nitric
      oxide (NO.). The oxygen radical superoxide (O2.-) and the nonradical hydrogen
      peroxide (H2O2) are produced during normal metabolism and perform several useful
      functions. Excessive production of O2.- and H2O2 can result in tissue damage,
      which often involves generation of highly reactive hydroxyl radical (.OH) and
      other oxidants in the presence of "catalytic" iron or copper ions. An important
      form of antioxidant defense is the storage and transport of iron and copper ions
      in forms that will not catalyze formation of reactive radicals. Tissue injury,
      e.g., by ischemia or trauma, can cause increased metal ion availability and
      accelerate free radical reactions. This may be especially important in the brain
      because areas of this organ are rich in iron and CSF cannot bind released iron
      ions. Oxidative stress on nervous tissue can produce damage by several
      interacting mechanisms, including increases in intracellular free Ca2+ and,
      possibly, release of excitatory amino acids. Recent suggestions that free radical
      reactions are involved in the neurotoxicity of aluminum and in damage to the
      substantia nigra in patients with Parkinson's disease are reviewed. Finally, the
      nature of antioxidants is discussed, it being suggested that antioxidant enzymes
      and chelators of transition metal ions may be more generally useful protective
      agents than chain-breaking antioxidants. Careful precautions must be used in the
      design of antioxidants for therapeutic use.

PMID- 1402909
TI  - Cloning and characterization of the cDNA encoding a novel brain-specific 14-kDa
      protein.
AB  - A new acidic protein with a molecular weight of 14,000 was purified from rat
      brain, in which it was specifically expressed, and partially sequenced by protein
      sequencing. On the basis of results obtained from the amino acid sequences, mixed
      oligonucleotides were synthesized and used as probes to clone a cDNA from a rat
      brain cDNA library. The cloned cDNA provided the full-length sequence of the 14
      kDa protein. Northern blot hybridization using total RNA from several tissues of
      the rat provided evidence that the 14-kDa protein was expressed specifically in
      rat brain. Transfection of this cDNA into mammalian cells resulted in expression
      of the 14-kDa protein. The amino acid sequence predicted from the cDNA of the rat
      brain 14-kDa protein contained 137 amino acid residues. A hydropathy profile
      revealed a hydrophobic domain (amino acids 60-80) flanked by highly hydrophilic
      stretches on both sides. Whereas the N-terminal region of the 14-kDa protein
      contained four repeating motifs, EKTKEGV, the C-terminal domain was rich in
      glutamic acid and proline. A computer search of the amino acid sequence of the 14
      kDa protein indicated no homology to any other protein reported so far.

PMID- 1402910
TI  - Lipid composition in different regions of the brain in Alzheimer's disease/senile
      dementia of Alzheimer's type.
AB  - The lipid compositions of 10 different brain regions from patients affected by
      Alzheimer's disease/senile dementia of Alzheimer's type were analyzed. The total
      phospholipid amount decreased somewhat in nucleus caudatus and in white matter.
      The cortical areas that are morphologically affected by Alzheimer's disease,
      i.e., frontal and temporal cortex and the hippocampus, showed elevated contents
      of lipid solvent-extractable phosphatidylinositol. Sphingomyelin content was
      decreased in regions rich in myelin. There was a 20-50% decrease in dolichol
      amount in all investigated parts of the brain, but no change was seen in the
      polyisoprenoid pattern. Levels of alpha-unsaturated polyprenes were decreased in
      Alzheimer brains. Dolichyl-phosphate content increased in most regions, up to
      100%. In both control and Alzheimer tissue almost all of the dolichyl-phosphate
      was covalently bound, apparently through glycosylation. Cholesterol amounts were
      highly variable but mostly unchanged, whereas ubiquinone concentrations increased
      by 30-100% in most regions in brains affected by Alzheimer's disease. These
      results demonstrate that both phospholipids and neutral lipids are modified in
      brains affected by Alzheimer's disease/senile dementia of Alzheimer's type.

PMID- 1402911
TI  - Developmental changes in beta-citryl-L-glutamate concentration and its synthetic
      and hydrolytic activities in neuronal cells cultured from chick embryo optic
      lobes.
AB  - Developmental changes in the concentration of beta-citryl-L-glutamate(beta-CG)
      have been examined in the cerebrum and optic lobe of the developing chick brain
      and in primary cultured neuronal cells from the chick embryo optic lobes with gas
      chromatographic and HPLC methods originated in our studies. A sharp peak was
      shown by beta-CG, with a maximal concentration at 13 days of incubation in the
      optic lobe of the developing chick brain but decreasing markedly to adult levels.
      The developmental change in primary cultured neurons was similar to that in the
      optic lobe of the developing chick brain. Changes in synthetic and hydrolytic
      activities of beta-CG were studied during growth of primary cultured neurons.
      Incorporation of radioactivities from radiolabeled pyruvate and alanine into beta
      CG increased significantly on day 3 of culture, reaching a plateau on day 6,
      whereas that from radioactive glutamine and glutamate increased gradually from
      day 3 to day 12 of culture. The hydrolyzing enzyme activity of beta-CG during
      neuron growth was low until day 3 of culture, when it increased significantly
      until day 12. Similar developmental changes were observed in the developing chick
      embryo optic lobes.

PMID- 1402912
TI  - Modulation by GTP of basal and agonist-stimulated striatal adenylate cyclase
      activity following chronic blockade of D1 and D2 dopamine receptors: involvement
      of G proteins in the development of receptor supersensitivity.
AB  - Rats receiving injections of specific antagonists of dopamine receptors (SCH
      23390 for D1, haloperidol for D2, and haloperidol+SCH 23390) once daily for 21
      days develop a selective supersensitivity of the blocked receptors. To study the
      molecular correlates of these adaptive changes, we evaluated the involvement of
      GTP-binding proteins in the development of supersensitivity of dopamine
      receptors. By means of adenylate cyclase studies, we tested whether any of the
      treatments modified the functional response to GTP in striata dissected from
      control and treated rats. Our data show that the chronic blockade of D1 and/or D2
      receptors potentiates both basal and dopamine receptor-stimulated adenylate
      cyclase activity in response to GTP. D1 receptor up-regulation correlates with an
      increased adenylate cyclase response to GTP, whereas D2 receptor up-regulation is
      accompanied by an enhanced GTP-induced inhibition of enzyme activity, in both
      basal and receptor-activated conditions. This potentiation does not seem to match
      the changes in mRNA content of Gs and Gi alpha subunits. Unexpectedly, however, a
      significant increase in Gi alpha subunit mRNA was found after the chronic
      blockade of D1 receptors; this result could be explained by cross-regulation
      between GTP-binding protein-mediated pathways. This cross-regulation could serve
      as a protective mechanism whereby cells exposing up-regulated receptors protect
      themselves from a condition of hyperactivity of the adenylate cyclase enzyme.

PMID- 1402913
TI  - Biochemical characterization of recombinant human nerve growth factor.
AB  - Recombinant human nerve growth factor (rhNGF) was expressed and secreted by
      Chinese hamster ovary cells and purified to homogeneity using ion-exchange and
      reversed-phase (RP) chromatography. The isolated product was shown to be
      consistent with a 120-amino-acid residue polypeptide chain by amino acid
      composition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), RP-HPLC, and mass spectrometry and with an N-terminal sequence consistent
      with that expected from the cDNA for human nerve growth factor. By size-exclusion
      chromatography, rhNGF behaves like a noncovalent dimer. Limited enzymatic digests
      of the 120-residue monomer produced additional species of 118 (trypsin, removal
      of the C-terminal Arg119-Ala120 sequence) and 117 (trypsin plus carboxypeptidase
      B, removal of the C-terminal Arg118-Arg119-Ala120 sequence) residues. Each of
      these species was isolated by high-performance ion-exchange chromatography and
      characterized by amino acid and N-terminal sequence analyses, SDS-PAGE, RP-HPLC,
      and mass spectrometry. All three species were present in the digests as both
      homodimeric and heterodimeric combinations and found to be equipotent in both the
      chick dorsal root ganglion cell survival and rat pheochromocytoma neurite
      extension assays.

PMID- 1402914
TI  - Molecular properties of 5-hydroxytryptamine3 receptor-type binding sites purified
      from NG108-15 cells.
AB  - 5-Hydroxytryptamine3 (5-HT3) receptor-type binding sites were solubilised from
      NG108-15 mouse neuroblastoma x rat glioma hybrid cells using five different
      detergents [n-octyl-beta-D-glucoside, Triton X-100, 3-[3
      (cholamidopropyl)dimethylammonio]-1-propanesulphonate (CHAPS), sodium cholate,
      and deoxycholate] and the solubilisation efficiencies compared. The equilibrium
      binding, kinetic properties, and pharmacological profile of solubilised binding
      sites were similar to those of 5-HT3 receptor-type binding sites (5-HT3R) in
      membrane preparations determined using [3H]GR65630. The solubilised binding sites
      were purified using an affinity column constructed by coupling the high-affinity
      antagonist GR119566X to an Affi-Gel 15 resin. The affinity of purified 5-HT3R for
      [3H]-GR65630 was reduced threefold compared to the crude soluble preparation, but
      the pharmacological profile was similar. The sedimentation coefficient of the
      purified protein (11S, detergent: CHAPS) was determined by sucrose density
      gradient centrifugation. The apparent molecular mass of the detergent/binding
      site complex (370 kDa) was determined by size exclusion chromatography in the
      presence of n-dodecyl-beta-D-maltoside. Gel electrophoresis of the purified
      protein revealed bands at apparent molecular masses of 36, 40, 50, and 76 kDa.
      Electron microscopy of the negatively stained purified protein showed the
      presence of round particles of 8-9 nm diameter with a 2-nm stained pit in the
      centre, closely resembling the doughnut shapes described for nicotinic
      acetylcholine receptors.

PMID- 1402915
TI  - Regional effects of sodium valproate on extracellular concentrations of 5
      hydroxytryptamine, dopamine, and their metabolites in the rat brain: an in vivo
      microdialysis study.
AB  - The effects of sodium valproate (VPA; 100, 200, and 400 mg/kg, i.p.) on ventral
      hippocampal and anterior caudate putamen extracellular levels of dopamine (DA)
      and 5-hydroxytryptamine (5-HT) were examined using in vivo microdialysis. VPA
      induced dose-related increases in dialysate DA, 3,4-dihydroxyphenylacetic acid,
      and 5-HT in the ventral hippocampus. Anterior caudate putamen dialysate 5-HT was
      also dose dependently elevated by the drug, whereas DA levels tended to decrease
      with increasing VPA dose. In contrast, VPA (200, 400, and 800 mg/kg, i.p.)
      produced no significant elevation of DA in posterior caudate putamen dialysates,
      although 5-HT levels were significantly elevated at the 400- and 800-mg/kg doses.
      In all three regions studied, dialysate concentrations of 5-hydroxyindoleacetic
      acid and homovanillic acid remained at basal levels following VPA treatments. The
      results are discussed with regard to the possible anticonvulsant mode of action
      of VPA.

PMID- 1402916
TI  - Loss and Ca(2+)-dependent retention of scinderin in digitonin-permeabilized
      chromaffin cells: correlation with Ca(2+)-evoked catecholamine release.
AB  - Exposure of chromaffin cells to digitonin causes the loss of many cytosolic
      proteins. Here we report that scinderin (a Ca(2+)-dependent actin-filament
      severing protein), but not gelsolin, is among the proteins that leak out from
      digitonin-permeabilized cells. Chromaffin cells that were exposed to increasing
      concentrations (15-40 microM) of digitonin for 5 min released scinderin into the
      medium. One-minute treatment with 20 microM digitonin was enough to detect
      scinderin in the medium, and scinderin leakage levelled off after 10 min of
      permeabilization. Elevation of free Ca2+ concentration in the permeabilizing
      medium produced a dose-dependent retention of scinderin. Results were confirmed
      by immunofluorescence microscopy of digitonin-permeabilized cells. Subcellular
      fractionation of permeabilized cells showed that scinderin leakage was mainly
      from the cytoplasm (80%); the remaining scinderin (20%) was from the microsomal
      fraction. Other Ca(2+)-binding proteins released by digitonin and also retained
      by Ca2+ were calmodulin, protein kinase C, and calcineurins A and B. Scinderin
      leakage was parallel to the loss of the chromaffin cell secretory response.
      Permeabilization in the presence of increasing free Ca2+ concentrations produced
      a concomitant enhancement in the subsequent Ca(2+)-dependent catecholamine
      release. The experiments suggest that: (1) scinderin is an intracellular target
      for Ca2+, (2) permeabilization of chromaffin cells with digitonin in the presence
      of micromolar Ca2+ concentrations retained Ca(2+)-binding proteins including
      scinderin, and (3) the retention of these proteins may be related to the increase
      in the subsequent Ca(2+)-dependent catecholamine release observed in
      permeabilized chromaffin cells.

PMID- 1402917
TI  - Identification of G protein subtypes in peripheral nerve and cultured Schwann
      cells.
AB  - In this study, we investigated the expression of various G proteins in whole
      sciatic nerves, in myelin and nonmyelin fractions from these nerves, and in
      membranes of immortalized Schwann cells. In myelin, nonmyelin, and Schwann cell
      membranes we detected two 39-40-kDa pertussis toxin substrates that were resolved
      on separation on urea-gradient gels. Two cholera toxin substrates with apparent
      molecular masses of 42 and 47 kDa were present in nerve and brain myelin and in
      Schwann cell membranes. In these membranes, a third 45-kDa cholera toxin
      substrate, which displayed the highest labeling, was also present. Immunoblotting
      with specific antisera allowed the identification of G(o) alpha, Gi1 alpha, Gi2
      alpha, Gi3 alpha, Gq/G11 alpha, and the two isoforms of Gs alpha in nerve
      homogenates, nerve, and brain myelin fractions. In Schwann cell membranes we
      identified G(o) alpha, Gi2 alpha, Gi3 alpha, and proteins from the Gq family, but
      no immunoreactivity toward anti-Gi1 alpha antiserum was detected. In these
      membranes, anti-Gs alpha antibody recognized the three cholera toxin substrates
      mentioned above, with the 45-kDa band displaying the highest immunoreactivity.
      Relative to sciatic nerve myelin, the Schwann cell membranes revealed a
      significantly higher expression of Gi3 alpha and the absence of Gi1 alpha. The
      different distribution of G proteins among the different nerve compartments might
      reflect the very specialized function of Schwann cells and myelin within the
      nerve.

PMID- 1402918
TI  - A quantitative study of the Ca2+/calmodulin sensitivity of adenylyl cyclase in
      Aplysia, Drosophila, and rat.
AB  - Studies in Aplysia and Drosophila have suggested that Ca2+/calmodulin-sensitive
      adenylyl cyclase may act as a site of convergence for the cellular
      representations of the conditioned stimulus (Ca2+ influx) and unconditioned
      stimulus (facilitatory transmitter) during elementary associative learning. This
      hypothesis predicts that the rise in intracellular free Ca2+ concentration
      produced by spike activity during the conditioned stimulus will cause an increase
      in the activity of adenylyl cyclase. However, published values for the Ca2+
      sensitivity of Ca2+/calmodulin-sensitive adenylyl cyclase in mammals and in
      Drosophila vary widely. The difficulty in evaluating whether adenylyl cyclase
      would be activated by physiological elevations in intracellular Ca2+ levels is in
      part a consequence of the use of Ca2+/EGTA buffers, which are prone to several
      types of errors. Using a procedure that minimizes these errors, we have
      quantified the Ca2+ sensitivity of adenylyl cyclase in membranes from Aplysia,
      Drosophila, and rat brain with purified species-specific calmodulins. In all
      three species, adenylyl cyclase was activated by an increase in free Ca2+
      concentration in the range caused by spike activity. Ca2+ sensitivity was
      dependent on both calmodulin concentration and Mg2+ concentration. Mg2+ raised
      the threshold for adenylyl cyclase activation by Ca2+ but also acted
      synergistically with Ca2+ to activate maximally adenylyl cyclase.

PMID- 1402919
TI  - Reversibility of nimodipine binding to brain in transient cerebral ischemia.
AB  - Using autoradiography, we have measured the in vivo binding of [3H]nimodipine to
      brain in a rat model of reversible cerebral ischemia. Ischemia was induced by
      simultaneous occlusion of the middle cerebral artery (MCA) and ipsilateral common
      carotid artery by microaneurysm clips. Rats were studied after 15 min of ischemia
      (ischemic group) or after 45 min of reperfusion following 15 min of ischemia
      (reperfused group). Regional cerebral blood flow (CBF) was determined
      autoradiographically using [14C]iodoantipyrine in both ischemic (n = 6) and
      reperfused (n = 6) groups. During ischemia blood flow in the territory of the MCA
      was depressed and recovered to normal only in the distal territory of the MCA
      following reperfusion. [3H]Nimodipine binding in the ischemic group (n = 12) was
      elevated in ischemic brain regions and declined significantly (p < 0.01) in these
      regions in the reperfused group (n = 11). The ratio of the volume of cortex
      showing increased binding to the total volume of the forebrain was 0.113 +/-
      0.025 (mean +/- SD) in the ischemic group and declined to 0.080 +/- 0.027
      following reperfusion (p < 0.005). In general, infarct was only observed in
      regions showing persistent elevation of nimodipine binding following reperfusion
      as determined by histology performed in a separate group of rats (n = 8) after 24
      h of reperfusion. We conclude that increased nimodipine binding to ischemic
      tissue is initially reversible with prompt reestablishment of CBF and is a
      sensitive indicator of early and reversible ischemia-induced cerebral
      dysfunction.

PMID- 1402920
TI  - Amygdala kindling potentiates seizure-stimulated immediate-early gene expression
      in rat cerebral cortex.
AB  - Kindling induces long-term adaptations in neuronal function that lead to a
      decreased threshold for induction of seizures. In the present study, the
      influence of amygdala kindling on levels of mRNA for the immediate-early genes
      (IEGs) c-fos, c-jun, and NGF1-A were examined both before and after an acute
      electroconvulsive seizure (ECS). Although amygdala kindling did not significantly
      influence resting levels of c-fos mRNA in cerebral cortex, ECS-stimulated levels
      of c-fos mRNA (examined 45 min after ECS) were approximately twofold greater in
      the cerebral cortex of kindled rats relative to sham-treated controls. The
      influence of kindling on IEG expression was dependent on the time course of
      kindling, as ECS-stimulated levels of c-fos mRNA were not significantly increased
      in stage 2 kindled animals. ECS-stimulated levels of c-jun and NGF1-A mRNA were
      also significantly increased in cerebral cortex of kindled rats relative to sham
      treated controls. The influence of kindling on IEG expression was long-lasting
      because an acute ECS stimulus significantly elevated levels of c-fos and c-jun
      mRNA in the cerebral cortex of animals that were kindled 5 months previously. In
      contrast to these effects in cerebral cortex, kindling did not influence ECS
      stimulated levels of c-fos mRNA in hippocampus. Finally, immunohistochemical
      studies revealed lamina-specific changes in the cerebral cortex.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1402921
TI  - Amygdala kindling alters protein kinase C activity in dentate gyrus.
AB  - Kindling is a use-dependent form of synaptic plasticity and a widely used model
      of epilepsy. Although kindling has been widely studied, the molecular mechanisms
      underlying induction of this phenomenon are not well understood. We determined
      the effect of amygdala kindling on protein kinase C (PKC) activity in various
      regions of rat brain. Kindling stimulation markedly elevated basal (Ca(2+)
      independent) and Ca(2+)-stimulated phosphorylation of an endogenous PKC substrate
      (which we have termed P17) in homogenates of dentate gyrus, assayed 2 h after
      kindling stimulation. The increase in P17 phosphorylation appeared to be due at
      least in part to persistent PKC activation, as basal PKC activity assayed in
      vitro using an exogenous peptide substrate was increased in kindled dentate gyrus
      2 h after the last kindling stimulation. A similar increase in basal PKC activity
      was observed in dentate gyrus 2 h after the first kindling stimulation. These
      results document a kindling-associated persistent PKC activation and suggest that
      the increased activity of PKC could play a role in the induction of the kindling
      effect.

PMID- 1402922
TI  - Pertussis toxin-insensitive G protein mediates carbachol activation of
      phospholipase D in rat pheochromocytoma PC12 cells.
AB  - In the present study, an activation mechanism for phospholipase D (PLD) in
      [3H]palmitic acid-labeled pheochromocytoma PC12 cells in response to carbachol
      (CCh) was investigated. PLD activity was assessed by measuring the formation of
      [3H]phosphatidylethanol ([3H]PEt), the specific marker of PLD activity, in the
      presence of 0.5% (vol/vol) ethanol. CCh caused a rapid accumulation of [3H]-PEt,
      which reached a plateau within 1 min, in a concentration-dependent manner. The
      [3H]PEt formation by CCh was completely antagonized by atropine, demonstrating
      that the CCh effect was mediated by the muscarinic acetylcholine receptor
      (mAChR). A tumor promoter, phorbol 12-myristate 13-acetate (PMA), also caused an
      increase in [3H]-PEt content, which reached a plateau at 30-60 min after
      exposure, but an inactive phorbol ester, 4 alpha-phorbol 12,13-didecanoate, did
      not. Although a protein kinase C (PKC) inhibitor, staurosporine (5 microM),
      blocked PMA-induced [3H]PEt formation by 77%, it had no effect on the CCh-induced
      formation. These results suggest that mAChR-induced PLD activation is independent
      of PKC, whereas PLD activation by PMA is mediated by PKC. NaF, a common GTP
      binding protein (G protein) activator, and a stable analogue of GTP, guanosine 5'
      O-(3-thiotriphosphate) (GTP gamma S), also stimulated [3H]PEt formation in intact
      and digitonin-permeabilized cells, respectively. GTP, UTP, and CTP were without
      effect. Furthermore, guanosine 5'-O-(2-thiodiphosphate) significantly inhibited
      CCh- and GTP gamma S-induced [3H]PEt formation in permeabilized cells but did not
      inhibit the formation by PMA, and staurosporine (5 microM) had no effect on
      [3H]PEt formation by GTP gamma S.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402923
TI  - Effects of several cations on the neuronal uptake of dopamine and the specific
      binding of [3H]GBR 12783: attempts to characterize the Na+ dependence of the
      neuronal transport of dopamine.
AB  - We have studied the effects of several cations on (1) the neuronal uptake of
      [3H]dopamine ([3H]DA) and (2) the specific binding of 1-[2
      (diphenylmethoxy)ethyl]-4-(3-phenyl-2-[1-3H]propenyl)piperazi ne ([3H]GBR 12783)
      to a site associated with the neuronal carrier of DA, in preparations obtained
      from rat striatum. When studied under the same experimental conditions, both the
      uptake of [3H]DA and the binding of [3H]GBR 12783 were similarly impaired by the
      gradual replacement of NaCl by sucrose. In both processes, no convenient
      substitute for Na+ was found. Furthermore, potential substitutes of Na+ acted as
      inhibitors of the uptake with a rank order of potency as follows: K+ = Li+ > or =
      Cs+ > or = Rb+ > choline+ > Tris+ > sucrose, which was somewhat different from
      that observed in binding studies, i.e., Cs+ > Rb+ > choline+ > or = K+ > Li+ >
      Tris+ > sucrose. In the presence of either 36 mM or 136 mM Na+, [3H]DA uptake was
      optimal with 2 mM Mg2+, 1 mM K+, or 1 mM Ca2+. In contrast, higher concentrations
      of divalent cations competitively blocked the uptake process. K+ concentrations >
      50 mM impaired the specific binding, whereas in the millimolar range of
      concentrations, K+ noncompetitively inhibited the uptake. Decreasing the Na+
      concentration increased the inhibitory effect of K+, Ca2+, and Mg2+ on the
      specific uptake. An increase in NaCl concentration from 0 to 120 mM elicited a
      significant decline in the affinity of some substrates for the [3H]GBR 12783
      binding site. An uptake study performed using optimal experimental conditions
      defined in the present study revealed that decreasing Na+ concentration reduces
      the affinity of DA for the neuronal transport. We propose a hypothetical model
      for the neuronal transport of DA in which both Na+ and K+ membrane gradients are
      involved.

PMID- 1402924
TI  - Tolerance of low intracellular pH during hypercapnia by rat cortical brain
      slices: A 31P/1H NMR study.
AB  - Metabolic tolerance of low intracellular pH (pH(i)) was studied in well
      oxygenated, perfused, neonatal, rat cerebrocortical brain slices (350 microns
      thick) by inducing severe hypercapnia. In each of 17 separate experiments 80
      brain slices (approximately 3.2 g wet weight) were suspended in an NMR tube,
      perfused with artificial CSF (ACSF), and studied at 4.7 T with 31P and 1H NMR
      spectroscopy. Spectra obtained every 5 min monitored relative concentrations of
      lactate or high-energy phosphate metabolites, from which pH(i) and extracellular
      pH were determined. Unperturbed slice preparations were metabolically stable for
      > 10 h, with no significant changes occurring in pHi, ATP, phosphocreatine (PCr),
      inorganic phosphate, or lactate. Different levels of hypercapnia were produced by
      sequentially perfusing slices with the following different ACSF batches, each
      having previously been equilibrated with a specific mixture of CO2 in oxygen: (a)
      10% CO2, 15 min of perfusion; (b) 30% CO2, 15 min of perfusion; (c) 50% CO2, 15
      min of perfusion; (d) 70% CO2, 30 min of perfusion; (e) 50% CO2, 15 min of
      perfusion; (f) 30% CO2, 15 min of perfusion; and (g) 10% CO2, 15 min of
      perfusion. At the completion of this protocol slices were again perfused with
      fresh ACSF that was equilibrated with a 95% O2/5% CO2 gas mixture. In each of
      five separate 1H and 31P experiments, brain slices were recovered within 2 h
      after termination of exposure to high CO2. The pHi was determined from
      measurements of the chemical shift difference between phosphoethanolamine and
      PCr, using a calibration curve obtained for our preparation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1402925
TI  - Cytosolic free calcium and gene expression during chemical hypoxia.
AB  - Understanding the cellular response to hypoxia may help elucidate the role of
      altered oxidation in neuronal death or abnormal cell function. In PC12 cells, 30
      min of chemical hypoxia (i.e., KCN) reduced ATP concentrations by 92%, but
      diminished viability by only 10%. Ten minutes of hypoxia increased cytosolic free
      calcium ([Ca2+]i) 2.5-fold above control, but after 30 min of hypoxia, [Ca2+]i
      was slightly below that of nonhypoxic cells. Short periods of hypoxia also
      exaggerated the K(+)-induced elevation of [Ca2+]i, but by 30 min these ATP
      depleted cells reestablished a calcium gradient that was equal to nonhypoxic,
      K(+)-depolarized cells. Thus, 30 min of severe ATP depletion left [Ca2+]i and
      viability relatively unaffected. Nerve growth factor caused slight, but
      significant, improvements in ATP and viability of hypoxic cells, but had no
      effect on [Ca2+]i. Although [Ca2+]i was equivalent in control and hypoxic cells
      after 30 or 60 min, hypoxia abolished the K(+)-stimulated elevation of [Ca2+]i.
      The nerve growth factor induction of c-fos, an indicator of the genomic response,
      was diminished by approximately 80%. Thus, hypoxic PC12 cells with greatly
      reduced ATP stores maintained normal [Ca2+]i, but their ability to respond to
      external stimulation was impaired. Further, the reduced oxidation that occurs in
      the brain in a variety of pathological conditions may interfere with the cellular
      response to stimulation and growth factors.

PMID- 1402926
TI  - Myelin gangliosides of human peripheral nervous system: an enrichment of GM1 in
      the motor nerve myelin isolated from cauda equina.
AB  - Myelins of the PNS were isolated from human motor and sensory nerves of cauda
      equina, and their ganglioside compositions were compared. The predominant
      ganglioside in the human PNS myelins, both from motor and sensory nerves, was LM1
      (sialosylneolactotetraosylceramide). Sialosyl-nLc6Cer and disialosyl-nLc4Cer,
      GD3, GM3, and GD1b were detected as common components of the two nerve myelins.
      Furthermore, it was revealed that the motor nerve myelin contained GM1 (about 15%
      of total gangliosides), whereas sensory nerve myelin contained only a trace
      amount of GM1 (less than 5%), by TLC analyses together with TLC immunostaining
      using anti-GM1 antibody. As for the disialoganglioside fraction, the content of
      GD1a, as well as that of GM1, differed in motor and sensory nerves. Thus, the
      different contents of the ganglioseries gangliosides in human motor and sensory
      nerve myelins were demonstrated.

PMID- 1402927
TI  - Sodium dependence of [3H]paroxetine binding and 5-[3H]hydroxytryptamine uptake in
      rat diencephalon.
AB  - The sodium dependence of binding of [3H]-paroxetine, a selective serotonin uptake
      inhibitor, to the serotonin transporter in rat diencephalon was studied in both
      brain membranes and tissue sections and compared with that of 5
      [3H]hydroxytryptamine ([3H]5-HT) uptake by synaptosomes from the same region.
      Binding of [3H]-paroxetine in both the membranes and sections displayed clear
      sodium dependence until a plateau occurring at 60 nM NaCl, the EC50 for sodium
      being 8 and 25 mM, respectively. The affinity (1/KD) of [3H]paroxetine binding
      was a simple hyperbolic function of sodium concentration. In contrast, the
      density of [3H]paroxetine sites was not affected by external Na+ concentration.
      The uptake of [3H]5-HT showed a similar pattern of sodium dependence with an EC50
      for Na+ of 25 mM. Both the affinity (1/Km) and the rate (Vmax) of [3H]5-HT uptake
      were dependent on external [Na+] with sodium-dependence curves fitting a
      rectangular hyperbola. The kinetic analysis of results indicates that one sodium
      ion is required for the binding of [3H]paroxetine as well as for the binding and
      translocation of each [3H]5-HT molecule. The results concur with a single-site
      model of the sodium-dependent serotonin transporter with common or overlapping
      domains for 5-HT and 5-HT uptake inhibitors.

PMID- 1402928
TI  - Endopeptidase 24-16 in murines: tissue distribution, cerebral regionalization,
      and ontogeny.
AB  - The tissue distribution, cerebral regionalization, and ontogeny of endopeptidase
      24-16 were established in murines by means of its quenched fluorimetric
      substrate, Mcc-Pro-Leu-Gly-Pro-D-Lys-Dnp, and its selective dipeptide blocker,
      Pro-Ile. Endopeptidase 24-16 was particularly abundant in the liver and kidney,
      and the lowest specific activity was detected in the heart. In the brain, a 16
      fold difference in specific activity was observed between the poorest and the
      richest cerebral areas. Endopeptidase 24-16 appeared in high concentrations in
      the olfactory bulb and tubercule, cingulate cortex, medial striatum, and globus
      pallidus, and was particularly weak in the CA1, CA2, and CA3 parts of the
      hippocampal formation and in the cerebellum. Endopeptidase 24-16 content in
      thirteen thalamic nuclei indicated a rather homogeneous distribution. This
      homogeneity was not observed in the hypothalamus, where pronounced variations
      occurred between enriched zones such as suprachiasmatic and arcuate nuclei and
      relatively poor areas such as periventricular and supraoptic nuclei.
      Endopeptidase 24-16 appeared to be developmentally regulated in the mouse brain;
      it was already detected at the fetal stage, increased transiently after birth,
      then regularly declined until adulthood.

PMID- 1402929
TI  - Relationship between plasma and brain large neutral amino acids in rats fed diets
      with different compositions at different times of the day.
AB  - Large neutral amino acids (LNAAs) compete with each other for carrier-mediated
      transport through the blood-brain barrier into the brain. The relative plasma
      concentration, expressed as the ratio of each LNAA to the sum of LNAAs, is
      considered the main regulator of brain LNAA concentrations. In order to
      investigate the consistency of this assumption throughout a 24-h period, we have
      compared the relationship of plasma LNAAs to brain LNAAs among groups of rats fed
      diets containing various amounts of protein (in order to obtain a wide range of
      plasma LNAA levels) at two different phases of the light/dark cycle (0900 and
      2100 hours). The relationship between plasma and brain LNAAs was found to be
      dependent on both diet and the time of day. Similar plasma amino acid
      concentrations in the morning and in the evening contrasted with different brain
      concentrations. Furthermore, previous findings that brain LNAA concentrations are
      influenced by plasma amino acid concentrations were confirmed.

PMID- 1402930
TI  - Characterization of gene organization and promoter region of the rat dopamine D1
      receptor gene.
AB  - Genomic and cDNA clones encoding the rat D1 receptor were isolated and sequenced.
      Comparison of the D1 receptor cDNA and genomic sequences revealed that the rat D1
      receptor gene is organized into two exons separated by a small intron in the 5'
      untranslated region of its mRNA. The transcription start site is located 864 bp
      upstream from the translational initiation site. The 5'-flanking sequences of the
      D1 receptor gene do not contain TATA and CAAT canonical sequences, but have a
      high G+C content, potential cyclic AMP and glucocorticoid response element
      sequences, and binding sites for transcription factors such as Sp1, Ap1, and Ap2.
      Transfection studies using the D1 5'-flanking sequence and CAT gene fusion
      constructs have demonstrated that (1) the D1 promoter is active in D1-expressing
      neuroblastoma NS20Y cells, but inactive in D1-deficient glioma C6 and kidney 293
      cells, (2) the information contained within 735 bp of 5'-flanking sequence of the
      D1 gene appears to be sufficient to confer its cell-specific expression, and (3)
      the D1 gene promoter responds to cyclic AMP induction, suggesting the existence
      of an auto-regulation mechanism by which the stimulation of D1 receptor exerts a
      positive feedback on its own gene expression.

PMID- 1402931
TI  - Rat brain creatine kinase messenger RNA levels are high in primary cultures of
      brain astrocytes and oligodendrocytes and low in neurons.
AB  - Rat brain creatine kinase (CKB) gene expression is highest in the brain but is
      also detectable at lower levels in some other tissues. In the brain, the CKB
      enzyme is thought to be involved in the regeneration of ATP necessary for
      transport of ions and neurotransmitters. To understand the molecular events that
      lead to high CKB expression in the brain, we have determined the steady-state
      levels of CKB mRNA in homogeneous cultures of primary rat brain astrocytes,
      oligodendrocytes, and neurons. Northern blot analysis showed that whereas the 1.4
      kb CKB mRNA was detectable in neurons, the level was about 17-fold higher in
      oligodendrocytes and 15-fold higher in astrocytes. The blots were hybridized with
      a CKB-specific 32P-antisense RNA probe, complementary to the 3' untranslated
      sequence of CKB, which hybridizes to CKB mRNA but not CKM mRNA. Also, the 5' and
      3' ends of CKB mRNA from the glial cells were mapped, using exon-specific
      antisense probes in the RNase-protection assay, and were found to be the same in
      astrocytes and oligodendrocytes. This indicated that (a) the site of in vivo
      transcription initiation in astrocytes and oligodendrocytes was directed
      exclusively by the downstream, nonconcensus TTAA sequence at -25 bp in the CKB
      promoter that is also utilized by all other cell types that express CKB and (b)
      the 3' end of mature CKB mRNA was the same in astrocytes and oligodendrocytes. In
      addition, there was no detectable alternate splicing in exon 1, 2, or 8 of CKB
      mRNA in rat astrocytes and oligodendrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402932
TI  - Activity and biospecificity of proteolyzed forms and dimeric combinations of
      recombinant human and murine nerve growth factor.
AB  - Purified recombinant human nerve growth factor (rhNGF) and submaxillary gland
      derived murine NGF (muNGF) were characterized by amino acid composition,
      polyacrylamide gel electrophoresis (PAGE), reversed-phase HPLC (RP-HPLC), and
      high-performance ion-exchange chromatography (HPIEC). Limited tryptic digest of
      the N and C termini of the 120-residue form of rhNGF produced a species of 109
      residues (10-118). The previously observed natural murine analogue of this
      variant, muNGF lacking the first eight N-terminal amino acids, was also isolated
      as a homodimer. Both species were purified using HPIEC and characterized by amino
      acid analysis, N-terminal sequence, PAGE, and RP-HPLC analysis. Each of the four
      homodimeric species was evaluated in some or all of the following biological
      assays for NGF: chick dorsal root and sympathetic ganglion assays and rat
      pheochromocytoma-12 cell line neurite extension assay. The 118-residue
      homodimeric versions of both rhNGF and muNGF displayed equivalent bioactivity,
      whereas the N terminal-modified molecules presented activity reduced by 50- to
      100-fold. Utilizing HPIEC, we have examined the ability of the monomeric forms of
      any two of the homogeneous dimeric species of rhNGF to recombine. We have shown
      that not only can all of the previously described species form dimers by
      recombination, but an interspecies dimer can be created between muNGF and rhNGF.

PMID- 1402933
TI  - Use of the neural cell adhesion molecule VASE exon by neurons is associated with
      a specific down-regulation of neural cell adhesion molecule-dependent neurite
      outgrowth in the developing cerebellum and hippocampus.
AB  - The development of the CNS is associated with an increasing use of the 30-bp
      variable alternative, spliced exon (VASE) in neural cell adhesion molecule
      (NCAM). We have assessed the relative usage of VASE by reverse transcriptase
      linked polymerase chain reaction in the developing cerebellum and hippocampus at
      times when neurons isolated from these tissues can respond to substrate
      associated NCAM by increased axonal growth and also at later developmental
      stages, when they are no longer responsive to substrate-associated NCAM. Neurons
      isolated from the developing cerebellum at postnatal day 6 respond to NCAM with
      increased neurite growth. NCAM transcripts from these cells were found to have
      negligible levels of VASE usage. In contrast, neurons that are isolated at later
      stages of development (postnatal days 8, 10, and 11) and do not respond to NCAM
      were found to synthesise a much higher proportion of NCAM transcripts containing
      VASE. In the hippocampus, embryonic day 18 neurons, which are responsive to NCAM,
      express low levels of VASE, whereas postnatal days 4 and 5 neurons, which are not
      responsive to NCAM, have a greater proportion of transcripts containing VASE.
      Thus, the level of NCAM VASE exon usage by neurons appears to be a good indicator
      of the ability of these cells to respond to non-VASE-containing NCAM (expressed
      in a cellular substratum) by increased neurite outgrowth.

PMID- 1402935
TI  - Management of recurrent dislocation of the patella following total knee
      arthroplasty.
AB  - Fifteen knees with patellar dislocation after total knee arthroplasty had
      realignment of the extensor mechanism using a modification of the Trillat
      procedure. The onset of dislocation occurred on average 4.7 months from the time
      of surgery. After total knee arthroplasty the patients had an average range of
      motion of 109 degrees. All patients had medialization of the tibial tubercle and
      lateral release. No patient had a recurrent dislocation after a minimum 2-year
      follow-up period. The average knee score was 82 and the average flexion arc was
      112 degrees. All but one of the osteotomies healed uneventfully.

PMID- 1402934
TI  - Porous-coated anatomic (PCA) knee arthroplasty. 3-year results.
AB  - During 1984-1986, the authors used the PCA total knee replacement system on 92
      knees in 86 patients who were followed for an average of 3.2 years (range, 2.2
      4.5 years). Of the 92 knees, 42 were treated due to rheumatoid arthritis (RA) and
      50 due to primary or secondary osteoarthrosis (OA). The average age of the
      patients was 60 years (range, 32-78 years). Seventy-one of the 92 prostheses were
      inserted without the use of methyl methacrylate cement. Fixation screws for the
      tibial plate were used in eight cases. One knee was revised due to ligamentous
      laxity by inserting a thicker tibia plate. Radiographically, there was
      radiolucency of more than 2 mm below two tibial plates (both RA), and four
      patellar components (2 RA, 2 OA; 4.3% of total) showed a radiolucent zone of 1 mm
      or more. Clinically, there were no evident loosenings. According to the Weinfeld
      scale, 80 knees (37 RA, 43 OA; P = NS) had an excellent result, 10 (6 OA, 4 RA)
      good, and 2 (1 OA, 1 RA) satisfactory. In comparison, the Hungerford scale gave
      47 excellent, 30 good, 14 satisfactory, and 1 poor result. These results reflect
      that cementless PCA total knee replacement also appears to provide good fixation
      in both OA and RA knees.

PMID- 1402936
TI  - Computerized templating in uncemented total hip arthroplasty to assess component
      fit and fill.
AB  - The aim of the uncemented femoral component in total hip arthroplasty is to
      achieve a stable bone-prosthesis interface without the use of polymethyl
      methacrylate (PMMA). Maximal fill of the femoral canal by the prosthesis promotes
      initial stability and long-term optimal stress transfer to the bone. The
      percentage "fit and fill" of the proximal femur by three prostheses, the porous
      coated anatomic, anatomic medullary locking, and the Harris-Galante, was compared
      by use of a computerized templating model to assess preoperative radiographs of
      20 patients. Results showed that overall percentage fit and fill was similar and
      satisfactory (greater than 60%) in 17 of 20 patients. If a satisfactory fill was
      not achieved with one prosthesis, another prosthesis did not significantly
      improve fill. Lack of bony contact in the proximomedial femur was the most common
      deficiency noted.

PMID- 1402937
TI  - Long-term results and survivorship analysis of 89 total condylar knee prostheses.
AB  - The results of 89 total condylar I prostheses were assessed using both the
      Hospital for Special Surgery rating system and survivorship analysis. At an
      average follow-up period of 9.5 years (range, 5-15) 61 patients (72 knees) were
      available for clinical and radiographic evaluation. Thirty (41.5%) knees were
      rated as excellent, 29 (40.5%) good, 4 (5.5%) fair, and 6 (8.5%) poor. Three (4%)
      cases were considered failures because they needed a second operation. Loss of
      the postoperative alignment often associated with lateral instability was
      observed in 23 knees. Loosening of the tibial plateau occurred in two knees; in
      one of these a successful revision was performed. Survivorship analysis, using
      deep infection and aseptic loosening as end-point criteria, gave a 15-year
      probability of survival of 95%. These results confirm the validity of the total
      condylar prosthesis and the reliability of cementation in knee arthroplasty.

PMID- 1402938
TI  - Unicondylar arthroplasty. A survivorship analysis.
AB  - A retrospective review of 52 cemented unicompartmental arthroplasties was
      undertaken to determine whether unicompartmental arthroplasty is an acceptable
      procedure for patients with isolated single-compartment disease. The average
      follow-up period was 8.3 years with a predicted survivorship of 93.75% at 10
      years post-arthroplasty. Results comparable to those for tricompartmental design
      were achieved at similar follow-up intervals. While stressing the importance of
      patient selection in this procedure, the authors feel that unicompartmental
      arthroplasty is a viable alternative to tricompartmental arthroplasty in the
      treatment of single-compartment disease. Further long-term survivorship analysis
      is necessary to conclude that unicompartmental results are equal to those of
      tricompartmental design.

PMID- 1402939
TI  - Bone ingrowth into a low-modulus composite plastic porous-coated canine femoral
      component.
AB  - Bone ingrowth into low-modulus canine femoral components made of composite
      plastics and porous coated with titanium fiber mesh was evaluated and compared to
      that found in femoral components of the same design made of titanium alloy and
      porous coated with titanium fiber mesh. Both types of components demonstrated
      extensive bone ingrowth into the porous coatings at 6 weeks and there were no
      differences in the histologic appearance of the tissue ingrowth in the two
      groups. The amount of bone that grew into the porous surface, the areal density
      of bone within the available pore space, and the extent of the prosthesis
      periphery with bone ingrowth were not significantly varied in the two different
      components. The results of this study show that adequate fixation of low-modulus
      composite femoral components porous coated with titanium fiber mesh by bone
      ingrowth can occur and that further investigation of these materials for femoral
      components may be warranted.

PMID- 1402940
TI  - Total knee arthroplasty in elderly patients. Comparison of tibial component
      designs.
AB  - The authors examined 98 total knee arthroplasties in 73 patients who were 80
      years of age or older at the time of surgery (average, 82 years; range, 80-90
      years). The follow-up period averaged 4.5 years (range, 2-12 years). The patients
      were divided into two groups based on their tibial component design. There were
      38 all-polyethylene tibial components in 28 patients and 60 metal-backed tibial
      components in 45 patients. There were 61 (62%) excellent, 30 (31%) good, 2 (2%)
      fair, and 5 (5%) poor results. Three of the five poor results required revision
      for septic failure. Of the knees with an all-polyethylene tibial component, 20
      (53%) were rated as excellent, 15 (39%) as good, and 3 (8%) as poor. One of these
      knees rated as poor required revision for septic failure. The knees with a metal
      backed tibial tray had 41 (68%) rated as excellent, 15 (25%) as good, 2 (3%) as
      fair, and 2 (3%) as poor. Both of the knees with poor results required revision
      for septic failure. Stratifying the results by component composition revealed 97%
      survival for both types of tibial trays. These results were obtained at 12 years
      for the all-polyethylene components and at 8 years for the metal-backed
      prosthesis. In conclusion, the authors believe that total knee arthroplasty is a
      reliable and durable procedure in the treatment of knee arthritis in the elderly.
      Elderly patients may represent a special case because they are generally less
      active than younger patients and may place less stress on their
      prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402941
TI  - Control of contamination of the operative team in total joint arthroplasty.
AB  - Reports of percutaneous transmission of blood-borne disease emphasize the need
      for control of intraoperative contamination. In a randomized prospective study,
      surgeons and surgical assistants involved in total hip and total knee
      arthroplasty adopted the following protocol: total body exhaust with hood,
      aspirator, knee-length impermeable gowns, foot covers, including knee-high covers
      and waterproof covers, and one of three combinations of gloving protocols:
      latex/latex changed hourly, latex/cloth, or latex/cloth/latex. All inner gloves
      were tested by a leak test. All needles and sharp instruments were passed on
      trays, and all contaminations and perforations were recorded. Each surgeon and
      assistant was inspected twice for contamination. There were no needle sticks, and
      only one of 267 personnel had head, neck, body, leg, or foot contamination.
      Perforation rates of inner gloves were 9.2% for latex/latex, 7.9% for
      latex/cloth, and 4.3% for latex/cloth/latex.

PMID- 1402942
TI  - The fate of massive allografts in total hip acetabular revision surgery.
AB  - A series of 23 major load-bearing acetabular allografts done in conjunction with
      revision total hip arthroplasty were prospectively evaluated. This study includes
      cases with a minimum 2-year follow-up period. The procedures were performed using
      noncemented porous-coated acetabular components with pegs. In seven acetabula
      there was no change in cup position when compared with the initial postoperative
      roentgenogram (35%). Six acetabula migrated 3-5 mm during the first 2 years, then
      became stable without further progression (28.6%). In six cases (30%) gross
      loosening and migration occurred, requiring revision to a larger cup. One case
      required exchange arthroplasty for infection (5%). All biopsies taken at the time
      of the revision for failure showed viable bone replacing allograft. If the
      criteria for success of major superior acetabular allografts include
      incorporation of the graft and long-term stability of the implant, then the
      success rate in this series is very low. Only 7 of 20 hips were successful over a
      relatively short time period. However, if expectations are lowered, and the
      procedure is considered successful if adequate bone stock is restored to the
      acetabulum to allow reconstruction with a cementless cup firmly fixed in viable
      bone, then all but three revisions were successful.

PMID- 1402943
TI  - Arthrodesis for failed ankle arthroplasty.
AB  - Thirty-eight ankles in 36 patients who underwent fusion for failed total ankle
      arthroplasty were reviewed. Twenty-two patients were women and 14 were men, and
      their mean age was 56.8 years. The fusion methods performed in the 38 ankles were
      malleolar resection in 13, intercalated bone graft in 20, and posterior
      tibiotalocalcaneal fusion in 5. Fixation was external in 36 ankles and internal
      in 2. Bone graft was used in 32 ankles. Union was achieved in 33 ankles (89%).
      The average duration of the follow-up period in 29 patients (31 ankles) was 8.3
      years (range, 2-14.4 years). Patients had no or mild pain in 24 ankles (80%).
      Complications occurred in five ankles (13%). Failed total ankle arthroplasty may
      be successfully salvaged by arthrodesis.

PMID- 1402944
TI  - Polyethylene debris-induced osteolysis and loosening in uncemented total hip
      arthroplasty. A cause of late failure.
AB  - Uncemented total hip arthroplasty has proven to be an acceptable alternative to
      cemented total hip arthroplasty with good short-term results. With the
      elimination of the use of polymethyl methacrylate for component fixation, failure
      at the bone-cement interface, with resultant osteolysis and progressive
      loosening, was thought to be preventable. Unfortunately the ultra-high-molecular
      weight polyethylene acetabular insert can wear and produce particulate debris.
      This debris can stimulate an osteolytic reaction and lead to late aseptic
      loosening in a cementless total hip arthroplasty.

PMID- 1402945
TI  - Interface corrosion of a modular head total hip prosthesis.
AB  - Wear and corrosion products released from metallic prosthetic joints can
      stimulate adverse reactions in the surrounding tissues that may eventually
      require revision of the prostheses. The authors report here a case of a modular
      total hip prosthesis removed after 35 months that showed evidence of corrosion
      and fretting at the Morse taper interface between the titanium alloy femoral stem
      and the cobalt-chromium ball.

PMID- 1402946
TI  - Stability of press-fit acetabular cups.
AB  - Mechanical tests were performed to characterize the initial stability of press
      fit cups as a function of cup design, surface structure, and surgical
      preparation. Eight cups from six manufacturers were press-fit into acetabular
      cavities prepared in two densities of Sawbones polyethylene foam and in bovine
      knee trabecular bone. Cavity sizes and cup loading forces were varied. Acetabular
      defects were simulated in the Sawbones model. Preparations were tested to
      determine axial-rotatory and tangential ("levering-out") stability. Results
      suggested that cup geometry and proper surgical technique--in particular, proper
      sizing and depth of the acetabular cavity--are important in determining initial
      cup stability independent of adjuvant screw or spike fixation. Stability is a
      function of the area of interface contact between the cup rim and the substrate.
      If the cavity is too small or too shallow, and the substrate too dense, the cup
      will not seat to the rim and stability will be compromised. If there are defects
      in the rim, the area of interface contact will be diminished and stability
      compromised. Cups with a true hemispherical design have a greater area of rim
      interface contact than "low-profile" cups and are therefore more stable. 1 mm
      undersizing of the cavity (or 2 mm undersizing in less dense substrate) appears
      to provide optimal stability.

PMID- 1402947
TI  - Displacement of an uncemented acetabular component after dislocation of a total
      hip prosthesis. A case report.
AB  - Review of the literature reveals few reports of complications encountered with
      noncemented acetabular components; most concern problems with screw or cup
      placement, component wear or migration, or disassembly of modular components. No
      reports involving the displacement of a noncemented acetabular component were
      found. This is a case report of a patient in whom a noncemented acetabular
      component was dislodged after the closed reduction of a dislocated total hip
      prosthesis 4.5 weeks after surgery. In light of this case, the authors believe
      these reductions should be performed under general anesthesia with fluoroscopic
      guidance. Care must be taken at surgery to ream sufficiently and obtain proper
      cup fit and position. Finally, the authors recommend bicortical screw fixation to
      provide maximum contact and rigid fixation in the early postoperative period.

PMID- 1402948
TI  - Pasteurella multocida infection of a total hip arthroplasty. A case report.
AB  - The authors report a case history of a diabetic woman requiring revision hip
      arthroplasty of a Charnley total hip prosthesis that was infected with
      Pasteurella multocida. The infection of the loose prosthesis followed a cat bite
      to the same leg. Advice is given on the management of patients with infection
      following animal inoculations, and the subject of increased risk with a loose
      prosthesis is discussed.

PMID- 1402949
TI  - Aspergillus infection of total knee arthroplasty presenting as a popliteal cyst.
      Case report and review of the literature.
AB  - Fungal infections have only rarely been reported to occur in patients having
      undergone total knee arthroplasty. This case report documents the first known
      case of Aspergillus fumigatus as the offending organism. Its initial presentation
      as a popliteal cyst further reinforces the known association of popliteal cysts
      and intra-articular knee pathology.

PMID- 1402951
TI  - Tibial intramedully devices in total knee arthroplasty.

PMID- 1402950
TI  - Titanium wear debris in failed cemented total hip arthroplasty. An analysis of 71
      cases.
AB  - Seventy-one cemented total hip arthroplasties (THAs) were reviewed following
      removal of the all-titanium alloy femoral stem. Fifty-one hips were primary
      arthroplasties that failed due to aseptic loosening, 8 were previous revisions
      with aseptic loosening, and 12 were removed for infection. The average duration
      of service for the three groups was 4.5 years, 5.0 years, and 3.7 years,
      respectively. Femoral bone loss in aseptically loose, primary THA was graded as
      severe in 51%, moderate in 24%, and mild in 20%. Femoral endosteolysis was
      present in 94%, while acetabular osteolysis was seen in 6%. Histological
      evaluation of tissues from failed primary arthroplasties revealed polymethyl
      methacrylate debris in 75% of cases, polyethylene debris in 80%, metal debris in
      75%, and chronic inflammatory cells in all cases. Metallic debris was not seen in
      the failed revision cases and in only 17% of the infected cases. Examination of
      retrieved femoral components revealed burnishing of the head in all cases, while
      71% of stems with aseptic loosening were abraded from the cement. Metal levels
      from 12 cases averaged 2,111 mg/g of dry tissue (range, 60-11,823); synovial
      fluid levels from 8 other cases averaged 106 mg/l (range, 22-340). While it is
      not certain whether metallic particles are a primary cause of loosening or are
      generated secondarily, their presence seems to accelerate bone loss and
      loosening.

PMID- 1402952
TI  - 11-oxoaerothionin: a cytotoxic antitumor bromotyrosine-derived alkaloid from the
      Caribbean marine sponge Aplysina lacunosa.
AB  - A new cytotoxic bromotyrosine-derived secondary metabolite, 11-oxoaerothionin
      [3], was isolated from the Caribbean sea sponge Aplysina lacunosa. The structure
      of 3 was argued on the basis of detailed spectroscopic analysis and by chemical
      conversion to the known antibiotic compound 11-hydroxyaerothionin [2]. When
      screened against a panel of four human cell lines, 11-oxoaerothionin [3] showed
      pronounced as well as selective antitumor activity toward the human colon (HCT
      116) cell line within the limited concentration range of 0.01-0.1 microgram/ml.

PMID- 1402953
TI  - New glycosphingolipids from the marine sponge Halichondria panicea.
AB  - A novel sphingolipid containing an iso-fatty acid, (4E,8E)-N-13'
      methyltetradecanoyl-1-O-beta-D-glucopyra nosyl-4-sphingadiene, was isolated from
      the Oregon marine sponge Halichondria panicea and its structure determined using
      a combination of spectroscopic and chemical degradation techniques. A second
      galactosyl-ceramide, which contained an unusually long chain fatty acid amide
      component, was also isolated from H. panicea.

PMID- 1402954
TI  - Coumarins from Phebalium tuberculosum ssp. megaphyllum and Phebalium filifolium.
AB  - A total of 14 coumarins have been isolated from the aerial parts of Phebalium
      tuberculosum ssp. megaphyllum and 9 from Phebalium filifolium (Rutaceae). Three
      of the coumarins obtained from P. tuberculosum ssp. megaphyllum are novel and
      have been characterized, on the basis of spectroscopic analysis, as (E)-7-(6
      hydroperoxy-3,7-dimethylocta-2,7- dienyloxy)coumarin [3], (E)-8-(6-hydroperoxy
      3,7-dimethylocta-2,7-dienyloxy)psoralen [16] and (E,E)-8-(7-hydroxy-3,7
      dimethylocta-2,5-dienyloxy)psoralen [15] In addition, both species yielded the
      simple acetophenone xanthoxylin, and P. tuberculosum ssp. megaphyllum gave (E)
      betulin-3-p-coumarate [20] and (Z)-betulin-3-p-coumarate [21], both of which
      appear to be novel. The chemotaxonomic implications of coumarin distribution in
      the two species are discussed.

PMID- 1402955
TI  - Homoscalarane sesterterpenes from Lendenfeldia frondosa.
AB  - The marine sponge Lendenfeldia frondosa, collected from the Solomon Islands, has
      yielded homoscalarane sesterterpenes. Two new metabolites, epihomoscalaralactone
      IIA [5] and homoscalarate II [10], were accompanied by two known metabolites,
      homoscalaralactone IIA [1] and homoscalaralactone IIB [7]. These structures were
      established by analysis of 2D nmr data, trends in 13C-nmr shifts, and comparison
      of experimental with molecular-mechanics-calculated nmr J's. Each of the alcohols
      1, 2, and 3 was converted to its corresponding acetate, 2, 6, and 8,
      respectively. Compound 6 exhibited moderate anti-inflammatory activity.

PMID- 1402956
TI  - Starfish saponins, 48. Isolation of fifteen sterol constituents (six glycosides
      and nine polyhydroxysteroids) from the starfish Solaster borealis.
AB  - This paper reports a complete steroid glycoside and polyhydroxysteroid analysis
      of the starfish Solaster borealis, collected at Mutsu Bay, Japan. The glycosides
      include a new pentaglycoside steroid sulfate ("asterosaponin"), designated
      solasteroside A [1], two new sulfated 24-O-diglycosides, both with the common 5
      alpha-cholesta-3 beta,6 alpha,8,15 alpha, 24-pentaol aglycone, borealosides A [2]
      and B [3], two new 24-O-(3-O-methyl)xylosides, borealosides C [4] and D [5],
      having the same aglycone with an additional hydroxy group at 4 beta-position in
      5, and the known amurensoside B, previously isolated from Asterias amurensis.
      Among the polyhydroxysteroid constituents, four (7-10) are new, and five (11-15)
      have previously been isolated from starfishes.

PMID- 1402957
TI  - Alkaloids from Psychotria oleoides with activity on growth hormone release.
AB  - Bioactivity-guided purification of a crude alkaloid extract of Psychotria
      oleoides has afforded a new alkaloid, psycholeine [1], together with quadrigemine
      C [2], a tetrameric pyrrolidinoindoline compound of unknown stereochemistry. A
      comparison study of nmr and cd spectra of quadrigemine C and hodgkinsine [3], a
      trimeric pyrrolidinoindoline substance, led us to suggest the stereochemistry of
      quadrigemine C. The structure and configuration of psycholeine was determined by
      spectroscopic means and chemical correlation with quadrigemine C. Psycholeine
      interacts with somatostatin receptors and exhibits a somatostatin antagonistic
      activity on GH secretion by pituitary cells in primary culture.

PMID- 1402958
TI  - New diketopiperazine metabolites from the sclerotia of Aspergillus ochraceus.
AB  - Three new diketopiperazine-containing metabolites 1-3 have been isolated from the
      sclerotia of Aspergillus ochraceus (NRRL 3519) by chromatography on Sephadex LH
      20 and reversed-phase hplc. The structures of these compounds were established
      using extensive high-field 1D and 2D nmr experiments. All three compounds cause
      moderate reduction in weight gain in assays against the lepidopteran crop pest
      Helicoverpa zea.

PMID- 1402959
TI  - Structures of four new triterpenoid oligoglycosides: DS-penaustrosides A, B, C,
      and D from the sea cucumber Pentacta australis.
AB  - Two new non-holostane-type triterpenoid oligoglycosides, DS-penaustrosides A [1]
      and B [2], were isolated from the solvolysate of a crude glycoside fraction
      obtained from a sea cucumber Pentacta australis, together with two holostane-type
      glycosides, DS-penaustrosides C [3] and D [4]. The structure of 1-4 have been
      elucidated on the basis of spectral and chemical evidence.

PMID- 1402960
TI  - An unusual fatty acid composition for a fresh-water mussel, Unio tumidus, from
      Bulgaria.
AB  - A combination of hplc in the silver ion mode and gc-ms of picolinyl ester
      derivatives was used to identify the fatty acids in a fresh-water mussel, Unio
      tumidus, from the Danube in Bulgaria. A number of novel fatty acids were found,
      including 14-methylpentadec-6-enoic and 17-methyloctadec-8-enoic acids. Eicos-7
      enoic acid was a major component.

PMID- 1402961
TI  - 4-acetylaplykurodin B and aplykurodinone B, two ichthyotoxic degraded sterols
      from the Mediterranean mollusk Aplysia fasciata.
AB  - Two ichthyotoxic lactones, 4-acetylaplykurodin B [1] and aplykurodinone B [2],
      were isolated from the external parts of the body of the mollusk Aplysia
      fasciata. Their structures, determined by spectroscopic and chemical means, are
      closely related to aplykurodin B [3] previously isolated from Aplysia kurodai.
      The interconversion of delta- and gamma-lactones in the aplykurodin derivatives
      has been also investigated.

PMID- 1402962
TI  - Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic
      agents.
AB  - Bioassay-directed fractionation of clove terpenes from the plant Eugenia
      caryophyllata has led to the isolation of the following five active known
      compounds: beta-caryophyllene [1], beta-caryophyllene oxide [2], alpha-humulene
      [3], alpha-humulene epoxide I [4], and eugenol [5]. Their structures were
      determined on the basis of spectral analysis (hreims, 1H and 13C nmr). These
      compounds showed significant activity as inducers of the detoxifying enzyme
      glutathione S-transferase in the mouse liver and small intestine. The ability of
      natural anticarcinogens to induce detoxifying enzymes has been found to correlate
      with their activity in the inhibition of chemical carcinogenesis. Thus, these
      sesquiterpenes show promise as potential anticarcinogenic agents.

PMID- 1402964
TI  - Do prophylactic anticonvulsant drugs alter the pattern of seizures after
      craniotomy?
AB  - A total of 276 patients with a high risk of developing postoperative seizures
      were randomised to treatment with carbamazepine or phenytoin for six or 24
      months, or to no treatment. No significant differences were found (though the
      confidence limits were fairly wide) between the regimes in respect of the
      incidence of seizures or death. In a substantial proportion of the patients
      postoperative epilepsy remained a continuing disability. A high incidence of drug
      related side effects was found in the treatment groups. Prophylactic
      anticonvulsants cannot therefore be recommended routinely following
      supratentorial craniotomy.

PMID- 1402963
TI  - The ocular manifestations of multiple sclerosis. 1. Abnormalities of the afferent
      visual system.

PMID- 1402965
TI  - A longitudinal assessment of seizure outcome and overall benefit from 100
      cortectomies for epilepsy.
AB  - Results of 100 cortical resections for 76 temporal, 23 frontal and one parietal
      lobe epilepsies were studied in terms of seizure relief and overall benefit. A
      non-homogenous Markov chain model was used to take into account both the
      intravariability of post-surgical outcome and the differences in duration of
      follow-up in a group of patients consecutively operated. The seizure free (SF)
      state was defined as no seizure in the previous five months at first follow up
      visit and none in the preceding 12 months at subsequent annual visits. For the
      whole of the population the SF probability was 82%, 66%, 61%, and 62% at six
      months, one year, two and five years respectively. A better outcome was found for
      temporal lobe epilepsy (SF probability: 68% at the fifth postoperative year) than
      for frontal lobe epilepsy (SF probability: 42% at the fifth postoperative year)
      with a statistically significant difference. Pre- and postoperative interictal
      signs and symptoms were classified according to their clinical significance: (a)
      mild handicap--symptoms recognisable but no interference with usual life, and (b)
      moderate or severe handicap--interference with some or all daily activities. The
      interictal state was considered more impaired after surgery than before in two
      situations: (a) either symptoms, absent before surgery, appeared in the
      postoperative period involving a moderate or severe handicap, or (b) symptoms
      present before surgery and answerable for a mild or moderate handicap that
      increased to involve a moderate or severe handicap respectively in the
      postoperative period. Surgery was considered a major benefit when two conditions
      were fulfilled-namely, a SF state and no deterioration of the interictal stage
      when compared with the preoperative period. The probability of obtaining such a
      benefit was 58%, 51%, 48% and 56% at six months, one year, two and five years
      respectively. The results suggest that surgery is an effective treatment for more
      than 50% of long lasting medically intractable epilepsies.

PMID- 1402966
TI  - Regional cerebral blood flow abnormalities in depressed patients with cognitive
      impairment.
AB  - Depression with cognitive impairment, so called depressive pseudodementia, is
      commonly mistaken for a neurodegenerative dementia. Using positron emission
      tomography (PET) derived measures of regional cerebral blood flow (rCBF) a cohort
      of 33 patients with major depression was studied. Ten patients displayed
      significant and reversible cognitive impairment. The patterns of rCBF of these
      patients were compared with a cohort of equally depressed non-cognitively
      impaired depressed patients. In the depressed cognitively impaired patients a
      profile of rCBF abnormalities was identified consisting of decreases in the left
      anterior medial prefrontal cortex and increases in the cerebellar vermis. These
      changes were additional to those seen in depression alone and are distinct from
      those described in neurodegenerative dementia. The cognitive impairment seen in a
      proportion of depressed patients would seem to be associated with dysfunction of
      neural systems distinct from those implicated in depression alone or the
      neurodegenerative dementias.

PMID- 1402967
TI  - Neurological stamp. Niels Stensen (or Steno) 1648-86.

PMID- 1402968
TI  - The effect of immunosuppression on the development of cerebral oedema in an
      experimental model of intracerebral haemorrhage: whole body and regional
      irradiation.
AB  - The oedema which forms around an intracerebral haemorrhage has a complex
      aetiology. The immune response may have a role in its formation. There is
      clinical and experimental evidence that circulating leucocytes and platelets may
      mediate oedema formation. Global depletion of circulating leucocytes and
      platelets by whole body irradiation in a rodent model of intracerebral
      haemorrhage was found to confer protection against both ischaemia and oedema
      formation. This was not a direct effect of irradiation of the brain. The possible
      mechanisms for this protection are discussed.

PMID- 1402969
TI  - Intracranial blood flow velocity after head injury: relationship to severity of
      injury, time, neurological status and outcome.
AB  - Middle cerebral artery (MCA) blood flow velocity was measured daily by
      transcranial Doppler ultrasonography in 121 patients with severe (50), moderate
      (16) and minor (55) head injury during their hospital stay, and the results
      compared with findings in control subjects. Admission MCA velocity was
      significantly lower after severe 35.8 (31.9-39.7) cm/s, mean (95% confidence
      limits), moderate 45.5 (40.0-51.0) cm/s and minor 51.7 (47.9-55.5) cm/s head
      injury when compared with normal controls 60.1 (56.9-63.3) cm/s. Initial mean
      velocity in severe head injury was significantly lower than in moderate and minor
      injury. At discharge, MCA velocity in severe injury remained below normal 46.2
      (43.2-49.0) cm/s, whereas, in moderate and minor injury flow velocity had
      returned to normal. Correlation (r = 0.46, p less than 0.01) was found between
      MCA velocity and Glasgow Coma Score (GCS) on admission but not on discharge.
      Persistently low flow velocity was found in all 10 patients who died within 72
      hours (early deaths). An admission MCA velocity of less than 28 cm/s correctly
      predicted 80% of the early deaths. Patients who made a good recovery or had only
      moderate disability at six months showed a significant increase in velocity from
      admission 36.2 (31.5-41.2) cm/s to discharge 47.8 (43.7-51.9) cm/s in contrast to
      those who were severely disabled, in whom velocity generally remained low.

PMID- 1402970
TI  - The combined monitoring of brain stem auditory evoked potentials and intracranial
      pressure in coma. A study of 57 patients.
AB  - Continuous monitoring of brainstem auditory evoked potentials (BAEPs) was carried
      out in 57 comatose patients for periods ranging from 5 hours to 13 days. In 53
      cases intracranial pressure (ICP) was also simultaneously monitored. The study of
      relative changes of evoked potentials over time proved more relevant to prognosis
      than the mere consideration of "statistical normality" of waveforms; thus
      progressive degradation of the BAEPs was associated with a bad outcome even if
      the responses remained within normal limits. Contrary to previous reports, a
      normal BAEP obtained during the second week of coma did not necessarily indicate
      a good vital outcome; it could, however, do so in cases with a low probability of
      secondary insults. The simultaneous study of BAEPs and ICP showed that apparently
      significant (greater than 40 mm Hg) acute rises in ICP were not always followed
      by BAEP changes. The stability of BAEP's despite "significant" ICP rises was
      associated in our patients with a high probability of survival, while
      prolongation of central latency of BAEPs in response to ICP modifications was
      almost invariably followed by brain death. Continuous monitoring of brainstem
      responses provided a useful physiological counterpart to physical parameters such
      as ICP. Serial recording of cortical EPs should be added to BAEP monitoring to
      permit the early detection of rostrocaudal deterioration.

PMID- 1402971
TI  - Spatiomotor cueing in unilateral left neglect: three case studies of its
      therapeutic effects.
AB  - Limb activation contralateral to a cerebral lesion seems to reduce visual
      neglect, though whether this is due to perceptual cueing or hemispheric
      activation is controversial. Three case studies are presented which attempt to
      use this experimental finding therapeutically in the rehabilitation of unilateral
      left neglect. The first study used a combination of perceptual anchoring training
      with left arm activation procedures and produced improvements. The second used
      the same method, but stimulated left arm activation using an avoidance
      conditioning procedure, again with positive results. The third case treatment
      focused on cueing for left arm activation without explicit instructions for
      perceptual anchoring, with positive results.

PMID- 1402972
TI  - The alien hand and related signs.
AB  - Alien limb sign includes failure to recognise ownership of one's limb when visual
      cues are removed, a feeling that one body part is foreign, personification of the
      affected body part, and autonomous activity which is perceived as outside
      voluntary control. Although the hand is most frequently affected, any limb or
      combination of limbs may fulfil the alien limb criteria. Alien hand sign should
      be reserved for cases in which the hand feels foreign together with observable
      involuntary motor activity. To characterise this phenomenon, seven patients with
      alien hand sign and other motor or behavioural manifestations are described.
      Aetiologies included multiple infarcts and cortobasal ganglionic degeneration
      (CBD). In this study, all patients had apraxia in response to verbal commands and
      problems with bimanual coordination. Most displayed non-goal directed involuntary
      motor activities, and two had self destructive motor behaviours. Grasp reflex
      occurred with alien hand due to either aetiology. Cortical reflex myoclonus was
      frequently seen in CBD patients. The phenomenological spectrum is reviewed, a
      diagnostic protocol proposed, and possible anatomical bases of alien hand
      discussed.

PMID- 1402973
TI  - Psychophysical correlates of phantom limb experience.
AB  - Phantom limb phenomena were correlated with psychophysiological measures of
      peripheral sympathetic nervous system activity measured at the amputation stump
      and contralateral limb. Amputees were assigned to one of three groups depending
      on whether they reported phantom limb pain, non-painful phantom limb sensations,
      or no phantom limb at all. Skin conductance and skin temperature were recorded
      continuously during two 30 minute sessions while subjects continuously monitored
      and rated the intensity of any phantom limb sensation or pain they experienced.
      The results from both sessions showed that mean skin temperature was
      significantly lower at the stump than the contralateral limb in the groups with
      phantom limb pain and non-painful phantom limb sensations, but not among subjects
      with no phantom limb at all. In addition, stump skin conductance responses
      correlated significantly with the intensity of non-painful phantom limb
      paresthesiae but not other qualities of sensation or pain. Between-limb measures
      of pressure sensitivity were not significantly different in any group. The
      results suggest that the presence of a phantom limb, whether painful or painless,
      is related to the sympathetic-efferent outflow of cutaneous vasoconstrictor
      fibres in the stump and stump neuromas. The hypothesis of a sympathetic-efferent
      somatic-afferent mechanism involving both sudomotor and vasoconstrictor fibres is
      proposed to explain the relationship between stump skin conductance responses and
      non-painful phantom limb paresthesiae. It is suggested that increases in the
      intensity of phantom limb paresthesiae follow bursts of sympathetic activity due
      to neurotransmitter release onto apposing sprouts of large diameter primary
      afferents located in stump neuromas, and decreases correspond to periods of
      relative sympathetic inactivity. The results of the study agree with recent
      suggestions that phantom limb pain is not a unitary syndrome, but a symptom class
      with each class subserved by different aetiological mechanisms.

PMID- 1402974
TI  - A timed test of swallowing capacity for neurological patients.
AB  - A timed test of swallowing capacity has been designed for use in patients with
      neurogenic dysphagia. Swallowing speed (ml/s) has been demonstrated to have high
      intra- and inter- rater and test- retest reliability, and to be essentially
      independent of flavour or temperature. "Guideline" normal values were established
      in individuals without a swallowing disorder: swallowing speed was less in
      females than males and declined in both groups with age. The validity of a
      swallowing speed less than 10 ml/s as an index of abnormal swallowing was tested
      by comparison with the complaint of abnormal swallowing in a group of 81
      neurological patients. Swallowing speed had a sensitivity of 96% and specificity
      of 69%: some apparent false positive responses were found in patients with
      disordered swallowing, mainly due to multiple sclerosis. Using a standard
      questionnaire and examination a similar pattern of symptoms and signs were
      statistically associated with both the clinical complaint of abnormal swallowing
      and swallowing speed. It is concluded that swallowing speed is a reliable and
      valid index for assessing disordered swallowing in neurological patients and may
      be of value in monitoring response to therapy.

PMID- 1402975
TI  - Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral
      nutrition.
AB  - Neuropathological examination of three patients who were maintained on parenteral
      nutrition without substitution of thiamine demonstrated an acute haemorrhagic
      encephalopathy. The lesions differed substantially from the classic features of
      thiamine deficient encephalopathy regarding the histopathological alterations and
      the topographical distribution. The extreme rapidity of thiamine deprivation may
      have been responsible for the abrupt clinical onset of the disease and the
      intensity of the morphological alterations.

PMID- 1402976
TI  - Lupus-related myelopathy: report of three cases and review of the literature.
AB  - Transverse myelopathy is an uncommon complication of systemic lupus erythematosus
      (SLE). Three patients with SLE are reported who developed transverse myelopathy,
      including the neuropathological findings in one patient on whom necropsy was
      performed. Paraparesis was present in all three cases, but definite sensory
      changes were present in only one patient. In two patients, the CSF findings were
      remarkable for elevated protein and depressed glucose concentrations. Microscopic
      examination of the brain demonstrated small, scattered foci of recent necrosis
      consistent with microinfarctions. Striking abnormalities were found in the spinal
      cord at all levels, including multiple foci of vacuolar spongy degeneration in
      the peripheral white matter, as well as ballooning of myelin sheaths, swollen
      axons, myelin pallor, and loss of glial nuclei. The pathological findings in
      previously reported cases of SLE-related transverse myelopathy are reviewed, and
      the possible pathogenesis of the findings in our case are discussed.

PMID- 1402978
TI  - MRI of anterior spinal artery syndrome.
AB  - In this serial MRI study a 24 year old man presenting anterior spinal artery
      syndrome was examined. In the acute stage, spin echo sequences showed an enlarged
      cervical cord on a T1 weighted image and high signal intensity in the enlarged
      portion of the cord on a T2 weighted image. The findings were interpreted as
      oedema in the grey and white matter subsequent to ischaemia. In the chronic
      stage, inversion recovery techniques revealed a distinct focus in the anterior
      two thirds of the cord at the low cervical level.

PMID- 1402977
TI  - Paraplegia due to a ruptured aneurysm of the distal posterior inferior cerebellar
      artery.
AB  - A case of paraplegia was due to a ruptured aneurysm of the distal posterior
      inferior cerebellar artery. The paraplegia was caused by a unilateral lesion
      located between the cervicomedullary junction and the C2 level, where it involved
      both crossed and uncrossed pyramidal fibres projecting to the lower extremities.
      Since a vascular lesion near the cervicomedullary junction is likely to be
      missed, special attention should be paid to this region when investigating
      subarachnoid haemorrhage with paraplegia.

PMID- 1402979
TI  - Unilateral upper cervical posterior spinal artery syndrome following sneezing.
AB  - A 35 year old man experienced severe transitory neck pain following a violent
      sneeze. This was followed by neurological symptoms and signs indicating a left
      sided upper cervical cord lesion. MRI showed an infarct at this site in the
      territory of the left posterior spinal artery. This discrete infarct was probably
      due to partial left vertebral artery dissection secondary to sneezing.

PMID- 1402980
TI  - Plus-minus lid syndrome.
AB  - A patient presented with ipsilateral ptosis and contralateral superior eyelid
      retraction due to a nuclear third nerve syndrome. The CT brain scan revealed a
      paramedian mesencephalic lesion contiguous with the oculomotor nucleus, sparing
      the midbrain tectum and the posterior commissure.

PMID- 1402981
TI  - Creutzfeldt-Jakob disease with congophilic kuru plaques: CT and pathological
      findings of the cerebral white matter.
AB  - In a patient whose Creutzfeldt-Jakob disease with congophilic kuru plaques that
      was proved at necropsy, the early brain CT showed low-density areas in the
      cerebral white matter before cortical atrophy and ventricular enlargement became
      apparent. Subsequently, there occurred diffuse white matter lucency and severe
      brain atrophy. At necropsy, there was severe white matter destruction which was
      more prominent than cortical neuronal loss. Serial CT scans were of great value
      for demonstrating the early and predominant changes in the cerebral white matter.

PMID- 1402982
TI  - Narcolepsy associated with primary temporal lobe B-cells lymphoma in a HLA DR2
      negative subject.
AB  - Narcolepsy and cataplexy began one year before treatment of a left mid-temporal
      primary B-cells lymphoma in a HLA DR2 negative man. Treatment with radio therapy
      and immunosuppression induced regression of the lymphoma and disappearance of
      narcolepsy and cataplexy.

PMID- 1402983
TI  - Lacunar thalamic stroke with pure cerebellar and proprioceptive deficits.
AB  - Case reports of two patients with cerebellar ataxia and proprioceptive sensory
      loss are presented. MRI of the brain revealed lesions of the ventroposterior part
      of the thalamus. These patients illustrate clinically the anatomical independence
      of cerebellar and sensory pathways in the thalamus. We suggest that the ataxic
      deficit is caused by interruption of cerebellar outflow pathways in the thalamus
      and not secondary to sensory deafferentation.

PMID- 1402984
TI  - Multiple sclerosis and hypertrophic demyelinating neuropathy.

PMID- 1402985
TI  - Unilateral vestibular paralysis as the sole manifestation of mumps.

PMID- 1402987
TI  - Pavor nocturnus from a brainstem glioma.

PMID- 1402986
TI  - Ataxic hemiparesis with cheiro-oral syndrome in capsular infarction.

PMID- 1402988
TI  - Octreotide--a new treatment for diarrhoea in familial amyloidotic polyneuropathy.

PMID- 1402989
TI  - Hypergraphia associated with a brain tumour of the right cerebral hemisphere.

PMID- 1402990
TI  - Clinical and laboratory findings with giant cell arteritis.
AB  - Out of 66 patients who were diagnosed as suffering from polymyalgia rheumatica
      (PMR; n = 40), temporal arteritis (AT; n = 14) or both (n = 12) in a 6.5 year
      period (incidence 3.4/100,000 per year), 9 died and 49 were followed up for an
      average period of 28 months. Exacerbations of the illness (n = 24) and
      complications in the course (n = 32) were more frequent with an initial ESR
      greater than 90 mm/h. Postural vertigo (n = 11), amaurosis fugax (n = 11) and
      polyneuropathy (n = 8) were the most frequent neurological complications.
      Persisting unilateral blindness and aromatic anosmia developed in 2 patients
      each. Complications were significantly more frequent in patients with initial
      symptoms of AT (chi 2 P less than 0.001). CRP-levels correlated better with
      persisting symptoms in the course than did the ESR. Recurrences after treatment
      were significantly more frequent when the length of corticosteroid-therapy was
      less than 20 months (chi 2 P less than 0.009). On follow up there were normal
      values for neopterin, tumour necrosis factor and antibodies against Borrelia
      burgdorferi.

PMID- 1402991
TI  - Presence of typical neuronal markers in serially cultured cells from adult human
      brain.
AB  - Typical markers for neurons but not for astroglia have been identified in cells
      cultured from a sample of normal adult human temporal lobe, which was removed to
      gain access to a glioma. Cells were grown in medium containing growth factors,
      including fibroblast growth factor and nerve growth factor. The cells grew slowly
      (doubling time, 18 days) and have been carried as far as passage 8 over 10
      months. Both immunoblotting and immunocytochemistry with redundant antibodies
      demonstrated the presence of neurofilaments (NF-H, NF-M, NF-L), but not glial
      fibrillary acidic protein (GFAP). Neuron-specific enolase (NSE) was also found.
      Morphologically, the cultures consisted of a pleimorphic population of cells with
      frequent long processes. Cells demonstrating neuronal rather than astroglial
      markers can be cultured from normal adult human brain.

PMID- 1402992
TI  - What determines the muscle cross-sectional area?

PMID- 1402993
TI  - Effect of high-dose methylprednisolone on anti-oxidant enzymes after experimental
      SAH.
AB  - Lipid peroxidation has been considered one of the most important factors involved
      in the pathogenesis of neuronal damage following subarachnoid hemorrhage. In the
      brain, the protective systems most involved against peroxidative and free
      radicals generated reactions are superoxide-dismutase (SOD) and glutathione
      peroxidase (GSH-Px). Since these activities are subjected to a significant
      reduction following experimental SAH induction in rats, we investigated in the
      present study if the beneficial effect of high-dose methylprednisolone (MP) in
      inhibiting lipid peroxidative processes in SAH is possibly linked to an influence
      on anti-oxidant enzymatic activities. In brain cortex, after MP treatment, Cu-Zn
      SOD activity in the early phase and more dramatically in the late phase after SAH
      was restored (4.06 +/- 0.06 and 4.07 +/- 0.14 enzymatic units/mg of protein,
      respectively) if compared to hemorrhagic non-treated controls (3.69 +/- 0.16 and
      2.96 +/- 0.06 enzymatic U/mg of protein) while Mn-SOD and GSH-Px activities were
      improved in treated animals only in the early and late phases after SAH,
      respectively. In the hippocampus, in treated rats Cu-Zn activity was partially
      restored only at 6 h, while Mn-SOD activity recovered at 48 h after SAH; no
      significant changes in GSH-Px activity were found in treated animals at any time.
      In the brain stem, in treated animals, Cu-Zn SOD activity was restored in the
      early phase (3.86 +/- 0.12 enzymatic U/mg of protein) up to control values of non
      hemorrhagic rats (3.44 +/- 0.30 enzymatic U/mg of protein), while GSH-Px activity
      recovered in the late phase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402994
TI  - Superficial siderosis of the central nervous system: report of three cases and
      review of the literature.
AB  - We present 3 cases and a review of the literature to demonstrate the current
      state of clinical diagnosis and therapy of superficial siderosis of the central
      nervous system. Typical symptoms were progressive cerebellar ataxia, spasticity
      and hearing loss. Repeated subarachnoid hemorrhage was indicated by persistent
      xanthochromia of the cerebrospinal fluid and confirmed by the presence of
      erythrophages, siderophages and iron-containing pigments. Deposition of free iron
      and hemosiderin in pial and subpial structures leads to intoxication of the
      central nervous system and represents the pathophysiological mechanism of
      superficial siderosis. Hypointensity of the marginal zones of the central nervous
      system on T2 weighted MR images indicates an iron-induced susceptibility effect
      and seems pathognomonic for superficial siderosis. In 39 of the 43 previously
      described cases superficial siderosis was verified by biopsy or autopsy. Today
      magnetic resonance imaging enables diagnosis at an early stage of the disease.
      Therapeutic management requires the elimination of any potential source of
      bleeding. In patients with unknown etiology no proofed therapy is yet available.

PMID- 1402995
TI  - Beta A4 deposition in the temporal cortex of adults with Down's syndrome.
AB  - The deposition of beta A4 has been quantified in the temporal cortex of 9 adults
      (4 male, 5 female) with Down's syndrome (DS), mean age (+/- SD) 54.7 +/- 8.8
      years (range 41-67 years) at the time of death. Immunostaining with antibodies,
      raised to different portions of the beta A4 protein, showed a greater number of
      deposits than were seen with traditional silver impregnation or amyloid stains.
      Antibody to beta A4(1-10) identified fewer plaques than the antibody to beta
      A4(12-28), the mean ratio of beta A4(1-10)/beta A4(12-28) plaques being 0.30 +/-
      0.10 (mean +/- SD). Morphologically, 'diffuse' and 'neuritic' deposits could be
      distinguished but there was no significant difference in the beta A4(1-10)/beta
      A4(12-28) ratio according to plaque morphology, nor did the ratio change with
      age. Quantitatively, the beta A4(12-28) load in the temporal cortex of DS
      patients was high, occupying some 14% of the field area, and it was not related
      to the age of the subject over the range studied. Similarly, the total beta A4(12
      28) plaque count was high and not age-related. The proportion of morphological
      plaque types visualised by the Glees and Marsland silver impregnation and by beta
      A4(12-28) immunostaining were compared. In both techniques 'diffuse' plaques (D)
      were predominant in the younger subjects and the proportion of 'neuritic' plaques
      (N) increased with age. The relative proportions of cored plaques (Cp) and plaque
      cores (C) did not change significantly with age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1402996
TI  - Cerebral cortical amyloid protein precursor mRNA expression is similar in
      Alzheimer's disease and other neurodegenerative diseases.
AB  - The expression of 3 beta-amyloid protein precursor (APP) mRNAs (695, 751, and
      770) in the cerebral cortex in Alzheimer's disease and other neurodegenerative
      diseases was analyzed by the S1 nuclease protection assay. We found no
      significant Alzheimer's disease-specific alteration of APP mRNA expression when
      compared to the other neurological diseases as controls. Since the expression of
      this mRNA was not correlated with amyloid deposition, it is possible that
      gliosis/neuronal loss may secondarily alter APP mRNA expression. However, the
      current study revealed no significant correlation between them.

PMID- 1402997
TI  - Postural inflexibility in parkinsonian subjects.
AB  - In order to identify the types of postural deficits seen in parkinsonian patients
      with postural instability, we compared the performance of parkinsonian subjects
      with young and old control subjects in 3 aspects of postural control: (1) the use
      of sensory information for postural orientation, (2) the coordination of postural
      movement patterns in response to surface displacements, and (3) the flexible
      modification of postural response patterns to changes in support conditions.
      Parkinsonian subjects had very small sway, even under altered sensory conditions.
      Postural response latencies to displacements were also normal. Postural
      instability was associated with abnormal patterns of postural responses including
      excessive antagonist activity and inflexibility in adapting to changing support
      conditions. Some parkinsonian subjects appeared to have difficulty sequencing
      motor programs for postural correction. The parkinsonian subjects appeared
      stiffer since the rate-of-change of sway in response to displacements was
      reduced. Levodopa improved postural coordination but not the flexible adaptation
      to changing support conditions.

PMID- 1402998
TI  - Blood glucose, glycosylated haemoglobin, and outcome of ischemic brain
      infarction.
AB  - From August 1987 through December 1989 all consecutive conscious patients younger
      than 70 years with a recent (less than 48 h) brain infarction of the carotid
      territory were prospectively included in the study. Blood samples for fasting
      blood glucose and glycosylated haemoglobin (HbA1c) were taken after a median
      delay of 23 h of the onset of symptoms. The severity of hemiparesis was assessed
      on admission, at 1 week, 3 weeks, and 3 months. The functional outcome was
      assessed at 3 months. Computed cerebral tomography was performed on admission,
      and later on at 3 weeks or 3 months. The brain infarct volume was measured from
      the CTs. The patients were diagnosed to have prestroke normoglycemia (n = 76) and
      prestroke hyperglycemia (n = 23) on basis of the HbA1c level. The case fatality
      rate, severity of hemiparesis, functional outcome, and infarct size did not
      differ between these 2 groups. On the other hand, fasting blood glucose level of
      the non-diabetics correlated strongly with the severity of hemiparesis and
      predicted stroke outcome. A statistically significant correlation was observed
      between blood glucose values and the volumes of cortical infarcts in non
      diabetics. Because prestroke blood glucose level, in contrast to post-stroke
      blood glucose level, did not have any predictive value concerning stroke outcome
      it is concluded that high fasting blood glucose values after stroke reflect a
      stress response to a more severe ischemic brain lesion.

PMID- 1403000
TI  - Serum levels of vitamin A in Parkinson's disease.
AB  - To elucidate a possible role of vitamin A in the pathogenesis of Parkinson's
      disease (PD) we compared serum levels of retinol (vitamin A), measured by HPLC,
      and the vitamin A/retinol binding protein (RBP) ratio of 42 PD patients (22 males
      and 20 females, mean age 67.3 +/- 1.34 years) and their respective spouses as
      control group (20 males and 22 females, mean age 66.2 +/- 1.42). The serum levels
      of vitamin A did not differ significantly between the 2 groups (0.59 +/- 0.03
      microgram/dl for PD patients and 0.57 +/- 0.03 microgram/dl for controls), nor
      did the vitamin A/RBP ratio (0.87 +/- 0.04 and 0.82 +/- 0.03, respectively).
      There was no influence of antiparkinsonian therapy on vitamin A or vitamin A/RBP
      ratio. Serum levels of vitamin A, and vitamin A/RBP ratio did not correlate with
      age, age at onset, scores of the Unified Parkinson's Disease Rating Scale or the
      Hoehn and Yahr staging in the PD group. These results suggest that serum
      concentrations of vitamin A, do not play a role in the pathogenesis of PD.

PMID- 1402999
TI  - Significance of CSF total neopterin and biopterin in inflammatory neurological
      diseases.
AB  - Total neopterin (T-N), a by-product in the biopterin biosynthesis and an
      indicator of activation of the cellular immune system, and total biopterin (T-B)
      levels in cerebrospinal fluid (CSF), were measured in patients with various
      inflammatory neurological diseases and Parkinson's disease, and the following
      results were obtained. (1) In patients with neuro-sarcoidosis, neuro-Behcet's
      disease and meningitis, CSF T-N levels were markedly elevated in the exacerbation
      or acute stages of their neurological symptoms and remarkably decreased in the
      remission or chronic stages. In the neuro-sarcoidosis and neuro-Behcet's disease
      patients, however, CSF T-B levels showed no substantial change. (2) There was a
      significant positive correlation between CSF T-N levels and CSF/serum albumin
      ratios only in the meningitis patients. However, increases of CSF T-N levels were
      not associated with those of plasma T-N levels. (3) In the Parkinson's disease
      patients, CSF T-N levels remained normal, although CSF T-B levels significantly
      decreased. (4) A gradient for the CSF T-N value (lumbar greater than ventricular
      CSF), being reverse to the CSF T-B value, was observed. These results indicate
      that the significance of CSF T-N is quite different from CSF T-B, and that CSF T
      N appears to be a valuable biochemical marker for evaluating the activity of
      inflammation within the central nervous system. Its measurement seems useful for
      therapeutic monitoring, especially of patients showing the chronic exacerbating
      remitting course.

PMID- 1403001
TI  - Cortical activity-associated negative myoclonus.
AB  - A patient with myoclonus epilepsy had 2 types of negative myoclonus as well as
      positive myoclonus at rest. One type followed a large EMG discharge at the end of
      continuous contraction and the other did not. Both types of negative myoclonus
      and positive myoclonus were preceded by EEG activity, predominantly distributed
      in the contralateral central region. It is suggested that an abnormal activity
      around the motor cortex suppresses a voluntary contraction as well as induces
      myoclonus. Clonazepam was markedly effective on both positive and negative
      myoclonus.

PMID- 1403002
TI  - Characterisation of dystrophin in fetuses at risk for Duchenne muscular
      dystrophy.
AB  - Dystrophin, the product of the Duchenne muscular dystrophy (DMD) gene, was
      studied in muscle from 16 human fetuses at risk for the disease. Eleven high risk
      (greater than 95% probability) and 5 low-risk (less than 25% probability) fetuses
      were studied with antibodies raised to different regions of the protein. All low
      risk fetuses showed a similar pattern to that of normal fetuses of a comparable
      age: using Western blot analysis, a protein was detected of similar size and
      abundance to that of normal fetuses (i.e. smaller molecular weight than that of
      adult muscle); immunocytochemistry showed uniform sarcolemmal staining in fetuses
      older than 18 weeks gestation and differential staining of myotubes at different
      stages of development (distinguished by size) in younger fetuses (less than 15
      weeks gestation). In contrast, Western blot analysis of high-risk fetuses
      detected low levels of dystrophin in 4 cases; 7 fetuses had no detectable
      protein. Immunocytochemistry with some dystrophin antibodies showed weak staining
      of the sarcolemma and around central nuclei in younger fetuses; in older fetuses
      there was little sarcolemmal staining with any antibody other than occasional
      positive fibres. These results indicate that careful study of dystrophin in
      fetuses at risk for DMD can be used to establish the clinical phenotype and
      provide additional information for future family counselling.

PMID- 1403003
TI  - Proliferation of human and mouse astrocytes in vitro: signalling through the
      protein kinase C pathway.
AB  - While several mitogens for astrocytes have been described, the signal
      transduction pathway(s) that mediates their proliferative effect remains unclear;
      in this report, a major role for the protein kinase C (PKC) system is suggested
      by several lines of evidence. Firstly, biologically active phorbol esters, 4 beta
      phorbol-12,13-dibutyrate and phorbol-12-myristate-13-acetate, increase the
      proliferation of astrocytes as determined by [3H]thymidine incorporation or
      bromodeoxyuridine immunofluorescence; this effect is not reproduced by a phorbol
      ester that binds to PKC but does not activate it (4 alpha-phorbol-12,13
      didecanoate). Secondly, 2 relatively selective inhibitors of PKC, H7 and
      staurosporine, attenuate the basal rate of proliferation of astrocytes in
      concentrations that were not cytotoxic to cells. Thirdly, mitogen-enhanced
      proliferation of astrocytes can be blocked by PKC inhibitors; this is observed
      for all astrocyte mitogens tested. Fourthly, measurements of PKC enzyme activity
      in astrocytes in response to serum-mitogenic factors, or to staurosporine,
      revealed a statistically significant correlation with proliferation rate. The
      mediation by PKC is not dependent on species- or age factors, since neonatal
      mouse or adult human astrocytes gave comparable results. The results have
      relevance to normal development and reactive gliosis post-injury, 2 conditions
      where astrocytes undergo proliferation, and to glioma growth.

PMID- 1403004
TI  - Myelination of regenerated axons in goldfish optic nerve by Schwann cells.
AB  - This study uses immunohistochemistry and EM to examine the site of injury in
      goldfish optic nerve during axonal regeneration. Within seven days of nerve crush
      axons begin to regrow and a network of GFAP+ reactive astrocytes appears in the
      nerve on either side of the injury. However, the damaged area remains GFAP-. By
      42 days after nerve crush, the sheaths of new axons acquire myelin marker 6D2,
      and the crush area becomes populated by a mass of longitudinally-orientated S
      100+ cells. Ultrastructurally, the predominant cells in the crush area bear a
      strong resemblance to peripheral nerve Schwann cells; they display a one-to-one
      association with myelinated axons, have a basal lamina and are surrounded by
      collagen fibres. It is proposed that these cells are Schwann cells which enter
      the optic nerve as a result of crush, where they become confined to the astrocyte
      free crush area.

PMID- 1403005
TI  - Regrowth of PNS axons through grafts of the optic nerve of the Browman-Wyse (BW)
      mutant rat.
AB  - We have examined the behaviour in vivo of regenerating PNS axons in the presence
      of grafts of optic nerve taken from the Browman-Wyse mutant rat. Browman-Wyse
      optic nerves are unusual because a 2-4 mm length of the proximal (retinal) end of
      the nerve lacks oligodendrocytes and CNS myelin and therefore retinal ganglion
      cell axons lying within the proximal segment are unmyelinated and ensheathed by
      processes of astrocyte cytoplasm. Schwann cells may also be present within some
      proximal segments. Distally, Browman-Wyse optic nerves are morphologically and
      immunohistochemically indistinguishable from control optic nerves. When we
      grafted intact Browman-Wyse optic nerves or 'triplets' consisting of proximal,
      junctional and distal segments of Browman-Wyse optic nerve between the stumps of
      freshly transected sciatic nerves, we found that regenerating axons avoided all
      the grafts which did not contain Schwann cells, i.e., proximal segments which
      contained only astrocytes; regions of Schwann cell-bearing proximal segments
      which did not contain Schwann cells; junctional and distal segments (which
      contained astrocytes, oligodendrocytes and CNS myelin debris). However, axons did
      enter and grow through proximal segments which contained Schwann cells in
      addition to astrocytes. Schwann cells were seen within grafts even after
      mitomycin C pretreatment of sciatic proximal nerve stumps had delayed outgrowth
      of Schwann cells from the host nerves; we therefore conclude that the Schwann
      cells which became associated with regenerating axons within the grafts of
      Browman-Wyse optic nerve were derived from an endogenous population. Our findings
      indicate that astrocytes may be capable of supporting axonal regeneration in the
      presence of Schwann cells.

PMID- 1403006
TI  - GAP-43 distribution is correlated with development of growth cones and
      presynaptic terminals.
AB  - GAP-43 (F1, B-50, pp46) has been associated with neuronal development and
      regeneration, but precise localization within neurons is not known. Pre-embedding
      electron microscopic immunocytochemistry using silver-enhanced 1 nm gold
      particles was used to localize GAP-43 label in cell cultures of cerebellar
      neurons. In the plasma membranes of early cultures, high levels of GAP-43 were
      seen in all parts of the neuron. In older cultures, consistent with previous
      reports, the first loss of GAP-43 label was seen in the soma and then the axon.
      Growth cones had high levels of GAP-43 label on the plasma membrane, with
      increased distribution over unattached relative to attached filopodia. The amount
      of GAP-43 seen over the plasma membrane of forming presynaptic terminals is lower
      than over growth cones, indicating a possible correlation between the presence of
      GAP-43 and the stage of presynaptic terminal development. Intracellular GAP-43 in
      axons and growth cones was highest in membranes of smooth cisternae. The levels
      of GAP-43 in smooth cisternae in axons fell by seven days in culture while the
      levels of GAP-43 in smooth cisternae of growth cones fell at 14 days. When mini
      explant cerebellar cultures were examined with light microscopic
      immunocytochemistry, GAP-43 label of plasma membrane was highest at the periphery
      of the radial axonal outgrowth, suggesting that addition of GAP-43 to the plasma
      membrane can occur in the distal axon or at the growth cone.

PMID- 1403007
TI  - Regeneration of axons in the optic nerve of the adult Browman-Wyse (BW) mutant
      rat.
AB  - We have studied the regeneration of axons in the optic nerves of the BW rat in
      which both oligodendrocytes and CNS myelin are absent from a variable length of
      the proximal (retinal) end of the nerve. In the optic nerves of some of these
      animals, Schwann cells are present. Axons failed to regenerate in the exclusively
      astrocytic environment of the unmyelinated segment of BW optic nerves but readily
      regrew in the presence of Schwann cells even across the junctional zone and into
      the myelin debris filled distal segment. In the latter animals, the essential
      condition for regeneration was that the lesion was sited in a region of the nerve
      in which Schwann cells were resident. Regenerating fibres appeared to be
      sequestered within Schwann cell tubes although fibres traversed the neuropil
      intervening between the ends of discontinuous bundles of Schwann cell tubes, in
      both the proximal unmyelinated and myelin debris laden distal segments of the BW
      optic nerve. Regenerating axons never grew beyond the distal point of termination
      of the tubes. These observations demonstrate that central myelin is not an
      absolute requirement for regenerative failure, and that important contributing
      factors might include inhibition of astrocytes and/or absence of trophic factors.
      Regeneration presumably occurs in the BW optic nerve because trophic molecules
      are provided by resident Schwann cells, even in the presence of central myelin,
      oligodendrocytes and astrocytes. All the above experimental BW animals also have
      Schwann cells in their retinae which myelinate retinal ganglion cell axons in the
      fibre layer. Control animals comprised normal Long Evans Hooded rats, BW rats in
      which both retina and optic nerve were normal, and BW rats with Schwann cells in
      the retina but with normal, i.e. CNS myelinated, optic nerves. Regeneration was
      not observed in any of the control groups, demonstrating that, although the
      presence of Schwann cells in the retina may enhance the survival of retinal
      ganglion cells after crush, concomitant regrowth of axons cut in the optic nerve
      does not take place.

PMID- 1403008
TI  - MHC-positive, ramified macrophages in the normal and injured rat peripheral
      nervous system.
AB  - Resident endoneurial macrophages form a prominent, but little recognized
      component of the PNS. We have studied immunocytochemically the distribution,
      morphology and immunophenotype of endoneurial macrophages in several normal
      peripheral nerves of the rat. In addition, we investigated the macrophage
      response following crush injury of the sciatic nerve. Resident endoneurial
      macrophages had a ramified morphology with processes oriented parallel to the
      long axis of nerve fibres. They were positive for several monocyte/macrophage
      markers such as ED1, ED2 and the recently-described MUC 101 and MUC 102
      antibodies. They furthermore expressed the complement type three receptor, the
      CD4 antigen and MHC class I and II molecules. These results were consistent in
      all the peripheral nerves studied. In addition, 1000 rad of gamma-irradiation led
      to a strong reduction in the number of MHC class II-positive ramified cells in
      the peripheral nerves similar to that observed in other peripheral organs such as
      the heart. A considerable percentage of resident macrophages in the PNS and/or
      their precursor cells are therefore radiosensitive and could be related to the
      lineage of dendritic cells. Following crush injury, ED1-3-, OX-42-, MUC 101- and
      MUC 102-positive round macrophages were observed from 24 h postlesion onward at
      the site of trauma. In the distal part, they were observed to form strings of
      round, foamy macrophages probably involved in myelin phagocytosis. In contrast,
      the number of MHC class II-positive resident macrophages was only slightly
      increased at the site of trauma and in the distal part. These cells transformed
      from a ramified to a round morphology, but did not appear as typical strings of
      foamy macrophages. These results demonstrate that the PNS is provided with a
      resident macrophage population analogous in many respects to microglial cells in
      the CNS. These constitutively MHC class II-positive PNS microglial-like cells
      could act as the major antigen-presenting cells in the peripheral nerve. They may
      thus constitute a local immune defense system of the PNS with a function similar
      to that of microglial cells in the CNS.

PMID- 1403009
TI  - Division and migration of satellite glia in the embryonic rat superior cervical
      ganglion.
AB  - While distinct precursors committed to a neuronal or glial cell fate are
      generated from neural crest cells early in peripheral gangliogenesis, little is
      known about the subsequent generation and maturation of young satellite glia from
      restricted glial precursor cells. To examine the division and migration of glial
      precursor cells and their satellite cell progeny, morphological,
      immunocytochemical and culture techniques were applied to the developing rat
      superior cervical ganglion. At embryonic day (E)18.5, numerous clusters of
      nonneuronal cells appeared transiently in the ganglion. Individual cells with a
      similar morphology were present in E16.5 ganglia, and are likely to represent the
      precursor cells which generate these clusters. The clustered cells were
      distinguishable from neighbouring neurons as well as from endothelial cells and
      fibroblasts. Morphologically similar cells were present in nerve bundles at E18.5
      and surrounding principal neurons and nerve bundles in the adult ganglion. Double
      label studies of the E18.5 ganglion with tyrosine hydroxylase to identify
      noradrenergic neurons and propidium iodide counterstaining to visualize all cell
      nuclei revealed that the cells in clusters stained with propidium iodide but
      lacked tyrosine hydroxylase immunoreactivity. To determine if cell clusters arose
      from division, bromodeoxy-uridine, a thymidine analogue, was administered to
      pregnant mothers between E16.5-E18.5, and ganglionic cells examined at E18.5 both
      in vivo and in vitro. Numerous non-neuronal cells divided during this period in
      situ and composed portions of clusters. When dissociated, superior cervical
      ganglion satellite glia reacted with an NGF-receptor antibody (MAb 217c) and
      possessed a flattened shape, in contrast to bipolar Schwann cells. Over half of
      the 217c-immunoreactive glia at E18.5 had incorporated bromodeoxyuridine during
      E16.5-18.5 in vivo. At birth, non-neuronal cells were no longer grouped in
      clusters, but were associated with neuronal cell bodies and processes. These
      findings suggest that, between E16.5-E18.5, glial precursors divide rapidly to
      form clusters, and that, after the peak of neurogenesis, daughter cells migrate
      within the ganglion to associate with nerve cell bodies and processes where
      proliferation continues at a slower rate. Distinct cellular and molecular
      interactions are likely to trigger the initial rapid division of glial
      precursors, initiate their migration and association with neuron cell bodies, and
      control their subsequent slower division.

PMID- 1403010
TI  - Hypertrophy and reversal of hypertrophy in rat pelvic ganglion neurons.
AB  - An experimental procedure which chronically reduces the lumen of the urethra in
      adult female rats produced distension of the bladder and conspicuous thickening
      of its wall, resulting within 6-8 weeks in a ten-fold increase in muscle weight
      (muscle hypertrophy). During this process, the neurons in the pelvic ganglion
      that innervate the bladder undergo a large increase in size (neuronal
      hypertrophy). The average neuronal volume increased by 83%; small neurons became
      less numerous and large neurons became more numerous than in controls, but there
      was no increase in the maximum neuronal size. Six weeks after re-operation and
      removal of the urethral obstruction, the weight of the bladder was reduced
      (although not quite to the control levels), while the average neuronal size
      reversed to values very close to controls. In separate experiments, the pelvic
      ganglion of one side was removed. The nerve fibres in the hemidenervated bladder
      sprouted, grew and spread to innervate the whole bladder. The neurons in the
      surviving pelvic ganglion hypertrophied, the average cell volume increasing by
      50% in seven weeks. The experiments showed that: (i) the pelvic neurons of adult
      rats are capable of very extensive growth when the tissue they innervate (bladder
      muscle) undergoes hypertrophy; (ii) the neuronal hypertrophy is reversible. This
      was taken to imply that there are factors within the bladder, including trophic
      substances, that regulate nerve cell volume not only by inducing growth but also
      by inducing the opposite effect, a cell size reduction; (iii) unilateral
      ganglionectomy, which did not induce muscle hypertrophy but doubled the amount of
      muscle innervated by the contralateral ganglion, was followed by marked neuronal
      hypertrophy.

PMID- 1403011
TI  - Evidence for supporting cell mitosis in response to acoustic trauma in the avian
      inner ear.
AB  - Acoustic overstimulation can lead to sensory cell (hair cell) loss in the
      auditory epithelium. Damaged hair cells in the organ of Corti (the mammalian
      auditory end-organ) degenerate and are replaced by non-sensory cells (supporting
      cells) which construct an irreversible scar. In birds, however, auditory hair
      cells which are damaged by acoustic trauma or ototoxic drugs may be replaced by
      new hair cells. As first step in determining the mechanism of hair cell
      regeneration, we developed an assay for cell divisions in the auditory epithelium
      after acoustic trauma. The results of these experiments demonstrate that
      supporting cells in damaged regions of the auditory epithelium incorporate the
      DNA-specific marker bromodeoxyuridine as early as one day after noise exposure.
      We provide direct evidence that following acoustic insult to the avian inner ear,
      supporting cells which reside within the sensory epithelium divide near the
      luminal surface and repopulate the epithelium. These results suggest that
      supporting cells participate in scar formation during hair cell degeneration, and
      produce new cells for regeneration.

PMID- 1403012
TI  - Localization of vasopressin-like immunoreactivity in the CNS of Aplysia
      californica.
AB  - Chromatographic and immunological evidence indicates that a vasopressin-like
      peptide might be present in the CNS of Aplysia californica, and that this peptide
      may be involved in modulating the behaviour of the gill. Immunocytochemical
      techniques using antisera raised against various vasopressin-like peptides were
      used to localize the sites containing these peptides in the CNS of Aplysia.
      Vasopressin-like immunoreactivity was found to be restricted to one single neuron
      in the abdominal ganglion and two small neurons located bilaterally in each pedal
      ganglion. Immunoreactive fibres were present in the neuropile of the abdominal,
      pedal, pleural and cerebral ganglia, but not in the buccal ganglion. The
      identification of these neurons provides a morphological localization for
      vasopressin-like substances detected previously in CNS extracts of Aplysia
      californica. In addition, the possibility of electrophysiological studies
      involving the immunoreactive neurons identified in the present paper will allow a
      more direct approach to study the physiological role of vasopressin-like peptides
      in Aplysia.

PMID- 1403013
TI  - Different kinds of axon terminals forming symmetric synapses with the cell bodies
      and initial axon segments of layer II/III pyramidal cells. III. Origins and
      frequency of occurrence of the terminals.
AB  - The cell bodies of the layer II/III pyramidal cells in rat visual cortex receive
      three morphologically distinct types of axon terminals. These axon terminals all
      form symmetric synapses and have been termed large, medium-sized, and dense axon
      terminals. The present study shows that each of these different kinds of axon
      terminals contains gamma-aminobutyric acid (GABA) which suggests that they are
      inhibitory. From an analysis of the profiles of 50 cell bodies it is calculated
      that the average layer II/III pyramidal cell has 65 axosomatic synapses, of which
      43 are formed by medium-sized terminals, 10 by large terminals, and 12 by dense
      terminals. Comparison of these different kinds of axon terminals with labelled
      axon terminals of known origin suggests that the medium-sized terminals are
      derived from smooth multipolar cells with unmyelinated axons, and that at least
      some of the dense terminals originate from bipolar cells that contain vasoactive
      intestinal polypeptides. The source of the large axon terminals is not known, but
      it is suggested that they originate from multipolar non-pyramidal cells with
      myelinated axons. Since the initial axon segments of these same neurons receive
      GABAergic axon terminals from chandelier cells, at least four different types of
      neurons provide inhibition to the cell bodies and axons of layer II/III pyramidal
      cells. This serves as an illustration of the complexity of the neuronal circuits
      in which pyramidal cells are involved.

PMID- 1403014
TI  - Optical imaging of brain function and metabolism. Garmisch-Partenkirchen, 21-22
      October 1991.

PMID- 1403015
TI  - The Guillain-Barre syndrome: no longer a simple concept.
AB  - Acute inflammatory demyelinating polyneuropathy or the Guillain-Barre syndrome
      (GBS) has come to be accepted as a clinical entity, although the boundary between
      it and chronic inflammatory demyelinating polyneuropathy has given rise to
      discussion. Recent observations have suggested that the GBS may represent the
      consequence of more than one pathogenetic mechanism. In most cases the salient
      pathological change is demyelination. In some this may be mediated predominantly
      by lymphocytes; in others, where the demyelination is produced primarily by
      macrophages, the process may be antibody-mediated. Both electrophysiological and
      pathological evidence indicates that occasional patients with the GBS show
      extensive axonal degeneration. Although this could represent a "bystander effect"
      secondary to inflammatory infiltration, at times it may reflect a direct attack
      on axons. Elucidation of the nature of the pathogenetic mechanisms is essential
      before rational therapy can be devised.

PMID- 1403016
TI  - rCBF abnormalities detected, and sequentially followed, by SPECT in neuro
      Behcet's syndrome with normal CT and MRI imaging.
AB  - Conventional imaging with computed tomography (CT) and magnetic resonance imaging
      (MRI) may show abnormalities in central nervous system Behcet's syndrome but is
      normal in some cases. Recently in two cases positron emission tomography has
      shown abnormalities in blood flow and glucose metabolism far more extensive than
      the abnormalities seen on CT and MRI scans in the same patients. We report a
      patient with neuro-Behcet's syndrome presenting with headache and personality
      change in whom CT and MRI brain imaging was normal, but regional cerebral blood
      flow imaging using single photon emission tomography with the tracer HMPAO showed
      extensive perfusion deficits which partially reversed after 3 months of
      prednisolone therapy. This technique may aid the diagnosis of cerebral
      involvement in Behcet's syndrome, although the cause and incidence of the
      perfusion deficits need further evaluation.

PMID- 1403018
TI  - Local botulinum toxin in the treatment of spastic drop foot.
AB  - Ten patients with spastic drop foot were treated by local injections of botulinum
      toxin A (botulinum toxin A haemagglutinin complex). The purpose was to improve
      stance and gait and/or to facilitate physiotherapy and patient care. Various calf
      muscles were injected using EMG guidance. The average dose used was 23 ng. Prior
      to and 4 weeks after treatment, positions of the upper and lower ankle joint at
      rest and the corresponding end positions of passive and active movement were
      determined. In addition, changes of spasticity and pain, the transmission
      phenomenon and stance and gait were evaluated. Most patients showed improvement
      of some aspects of the spastic drop foot. Positions of the upper and lower ankle
      joint were improved in most of the patients, as were the other parameters
      examined. Except for weakness of the injected muscles no side-effects were
      observed. The results appear promising and may be optimized in further trials by
      using higher doses of the toxin.

PMID- 1403017
TI  - Asymptomatic nerve hypertrophy in lepromatous leprosy: a clinical,
      electrophysiological and morphological study.
AB  - In order to learn more about early nerve lesions observed in leprosy, we
      performed a clinical, electrophysiological and morphological study in seven
      patients with untreated lepromatous leprosy, palpably enlarged radial cutaneous
      nerve and preserved sensation in the corresponding territory. The conduction
      velocity of the cutaneous radial nerve, which was decreased in all patients, did
      not significantly differ from that of a group of patients with lepromatous
      leprosy, hypertrophy of the radial cutaneous nerve and sensory loss. In contrast,
      the sensory action potential was significantly lower in patients with sensory
      loss, which demonstrates that axon loss is more important than demyelination in
      producing sensory loss. In all patients nerve enlargement was due to thickening
      of the epineurium and of the perineurium subsequent to inflammatory infiltrates
      and proliferation of fibroblasts and perineurial cells. In several fascicles, the
      inflammatory infiltrates and the infected cells infiltrated endoneurial
      connective tissue septa and blood vessels. Mycobacteria leprae were abundant in
      perineurial cells, fibroblasts, macrophages, Schwann cells and endothelial cells,
      and lymphocytic vasculitis present in all cases. The average density of
      myelinated fibres was 2600 SD 880 fibres/mm2 (control: 7700 fibres/mm2), with
      marked differences between individual fascicles, versus 420 fibres/mm2 in
      patients with nerve hypertrophy and sensory loss (range 0-2080 fibres/mm2).
      Single fibre preparations showed that segmental demyelination predominated in two
      patients, axonal degeneration in one, while inflammatory infiltrates and
      proliferation of connective tissue adhering to individual fibres were prominent
      in the others.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403019
TI  - Subacute diencephalic angioencephalopathy: an entity similar to angiodysgenetic
      necrotizing encephalopathy and Foix-Alajouanine disease.
AB  - A previously healthy 58-year-old man developed neurological illness with
      progressive dementia, hallucinations, central motor and vegetative impairment
      which led to death in 14 weeks. Autopsy revealed lesions in a symmetrical
      centrencephalic distribution. Inner cerebral veins and arteries were surrounded
      by extravasation of plasma and perivascular haemorrhage and were thickened by
      fibrous scarring and muscle fibre proliferation. Necrotized blood vessels were
      also found. The parenchyma was damaged by incomplete to complete necrosis. The
      age and sex of the patient, the progressive clinical course, the increase of
      cerebrospinal fluid protein, and the histopathology of the lesion show some
      similarities to angiodysgenetic necrotizing encephalopathy and spinal Foix
      Alajouanine disease.

PMID- 1403020
TI  - Does hyperglycaemia play a role on the outcome of acute ischaemic stroke
      patients?
AB  - A consecutive series of 327 patients (188 males, 139 females; mean age 68.4, SEM
      1.33) were hospitalized within 12 h of the onset of their first-ever hemispheric
      infarct. Three groups of patients were identified: diabetics (n = 70), non
      diabetic hyperglycaemics (n = 93) and normoglycaemics (n = 164). Case-fatality
      ratios at 30 days after stroke were 38.6%, 22.6% and 9.2% (P less than 0.001)
      respectively, whereas the causes of death and functional outcome of survivors
      were not significantly different between the groups. Mean admission serum glucose
      levels (SGLs) of decreased, impaired/unchanged and improved patients within each
      one of the three groups, were also not significantly different as opposed to
      their mean Canadian Neurological Scale (CNS) scores at entry (P less than 0.01).
      Among patients with less severe initial neurological deficit (i.e., CNS score
      greater than or equal to 7.0), 82.6% of non-diabetic hyperglycaemic subjects
      fared well, in comparison with 56.5% of diabetic and 70.1% of normoglycaemic
      individuals. The size of the infarcted areas at the second CT correlated with
      mean CNS scores (P less than 0.01) but not with mean SGLs on admission. The site
      of the ischaemic areas did not correlate with mean SGLs at entry. Therefore the
      influence of initial SGLs on the clinical course of the present series of
      patients is questionable or, alternatively, varied probably according to the
      pattern of residual cerebral blood flow after arterial occlusion.

PMID- 1403021
TI  - Cerebrospinal fluid cytokines in AIDS dementia complex.
AB  - We evaluated cerebrospinal fluid (CSF) and serum concentrations of interleukin-1
      alpha (IL-1-alpha), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF
      alpha) in 30 patients with AIDS dementia complex (ADC), and in 20 HIV
      seronegative subjects with other neurological diseases (OND). CSF TNF-alpha, IL-1
      alpha and IL-6 were more frequently detectable in ADC patients than in OND
      subjects. These cytokines were also detectable in CSF of ADC patients with
      minimal symptoms. In contrast, the majority of both ADC and OND patients did not
      contain detectable serum levels of cytokines. Our data support the notion of
      intrathecal synthesis of cytokines in ADC patients and raise the possibility that
      activated macrophages may play a significant role in the pathogenesis of ADC.

PMID- 1403022
TI  - The clinical use of apomorphine in Parkinson's disease.
AB  - Our 2-year experience in the therapeutic use of subcutaneous apomorphine has
      involved 25 patients with Parkinson's disease, 10 of whom continue to use it
      chronically. On the basis of this experience, we have formulated certain
      indications for its use, together with suggested approaches to modify patients'
      oral drug regimes so that apomorphine can best be deployed to improve their
      quality of life.

PMID- 1403023
TI  - Methionine in the treatment of nitrous-oxide-induced neuropathy and
      myeloneuropathy.
AB  - Two cases of severe myeloneuropathy and macrocytic anemia associated with a low
      serum level of vitamin B12 after prolonged exposure to nitrous oxide are
      reported. In both cases, the neurological manifestations worsened initially
      despite B12 supplementation, although in one case the use of methionine seemed to
      arrest the progression of the disease and accelerate recovery. This offers
      further support for the biochemical hypothesis of methionine synthetase
      inhibition by nitrous oxide and reproduces in man previously reported animal
      studies with methionine. Methionine may be an important first-line therapy in the
      initial treatment of neuropathy and myeloneuropathy induced by nitrous oxide, and
      has a hypothetical role in the treatment of subacute combined degeneration of the
      cord.

PMID- 1403024
TI  - Magnetic resonance imaging follow-up in Creutzfeldt-Jakob disease.
AB  - The history of a 67-year-old woman with histologically proven Creutzfeldt-Jakob
      disease (CJD) is presented. Before typical clinical and neurophysiological signs
      of CJD developed, magnetic resonance imaging (MRI) showed slightly enhanced
      signal intensity of the caudate nuclei and putamina in T2-weighted and proton
      density images, corresponding to spongiform degeneration in neuropathological
      examination. Five weeks later characteristical progressive cortical atrophy was
      demonstrated by follow-up MRI.

PMID- 1403025
TI  - Was it infarction or haemorrhage? A clinical diagnosis by means of the Allen
      score.
AB  - Since the clinical distinction between haemorrhagic and ischaemic stroke cannot
      be achieved with a simple clinical evaluation, and it is virtually impossible to
      submit all stroke patients to CT, a weighted clinical score may offer some
      advantages to physicians who are involved in stroke management. The Allen score
      (also referred to as the Guy's Hospital score), a validated clinical score, has
      been tested in two different clinical settings, comprising 289 patients. When
      only the values under 4 and those over 24 are taken into account (i.e. greater
      than 90% probability of ischaemia and haemorrhage), the global accuracy of the
      score is 97%, and the diagnostic gain (given a pretest probability for
      haemorrhage of 11% and a likelihood ratio of 194) is 85%. Therefore, we conclude
      that this simple clinical method can be used for epidemiological studies of
      stroke incidence and outcome, as well as for a first bedside screening to decide
      which patients should have priority for CT.

PMID- 1403026
TI  - Quantum chemical study on the interaction of some bisphosphonates and Ca2+: the
      role of molecular electrostatic potentials in the prediction of binding geometry.
AB  - Molecular electrostatic potentials have been used to model the calcium binding
      properties of some bisphosphonate drugs, which are used to treat various bone
      diseases. The mechanism of action involves the binding of bisphosphonates to the
      bone surface, where calcium plays an important role. Electrostatic potential maps
      derived from ab initio partial charges have been compared with both the crystal
      structure and the fully optimized ab initio structure of (dichloro)methylene
      bisphosphonate-calcium ion complex. Molecular electrostatic potentials can
      correctly predict the calcium binding geometry of bisphosphonate-type compounds
      and this type of information can be used in the practical drug design work.

PMID- 1403027
TI  - On the suitability of semiempirical calculations as sources of force field
      parameters.
AB  - The suitability of Dewar's Hamiltonians as a source of bonded force field
      parameters is explored from the comparison analysis between up to 270
      semiempirically derived force field parameters and experimentally derived values
      reported in some of the most popular force fields. From the statistical analysis
      of the results, some general conclusions about the semiempirical parametrization
      are formulated.

PMID- 1403028
TI  - Applications of rule-induction in the derivation of quantitative structure
      activity relationships.
AB  - Recently, methods have been developed in the field of Artificial Intelligence
      (AI), specifically in the expert systems area using rule-induction, designed to
      extract rules from data. We have applied these methods to the analysis of
      molecular series with the objective of generating rules which are predictive and
      reliable. The input to rule-induction consists of a number of examples with known
      outcomes (a training set) and the output is a tree-structured series of rules.
      Unlike most other analysis methods, the results of the analysis are in the form
      of simple statements which can be easily interpreted. These are readily applied
      to new data giving both a classification and a probability of correctness. Rule
      induction has been applied to in-house generated and published QSAR datasets and
      the methodology, application and results of these analyses are discussed. The
      results imply that in some cases it would be advantageous to use rule-induction
      as a complementary technique in addition to conventional statistical and pattern
      recognition methods.

PMID- 1403029
TI  - Automated site-directed drug design: the generation of a basic set of fragments
      to be used for automated structure assembly.
AB  - If a method is to be developed to assemble putative ligand structures in site
      directed drug design, from molecular graphs generated in the site, then basic
      building blocks are needed. Structure assembly is a combinatoric process that
      needs to be optimised if it is to be tractable. What has to be determined is
      whether small molecular fragments can have transferable properties from one
      molecule to another. In this paper we determine all possible combinations of 3-,
      4- and 5-atom aliphatic fragments from a small set of atoms H, C, N, O, F or Cl.
      The frequency of occurrence of these candidate fragments is searched for in the
      Cambridge Structural Database. A similar analysis is performed on charged
      fragments. A more restricted search is carried out for P and S and aromatic
      structures. A basic set of fragments can be derived that have a significant
      frequency in known crystal structures. The transferability of fragment properties
      is discussed in subsequent papers.

PMID- 1403030
TI  - Automated site-directed drug design: searches of the Cambridge Structural
      Database for bond lengths in molecular fragments to be used for automated
      structure assembly.
AB  - In this paper a database of small frequently occurring molecular fragments is
      used for the determination of fragment bond lengths from the Cambridge Structural
      Database. A large number of bond types are described that have not been reported
      previously.

PMID- 1403031
TI  - Automated site-directed drug design: an assessment of the transferability of
      atomic residual charges (CNDO) for molecular fragments.
AB  - In this paper a database of atomic residual charges has been constructed for all
      the molecular fragments defined previously in a combinatorial search of the
      Cambridge Structural Database. The charges generated for the atoms in each
      fragment are compared with charges calculated for whole molecules containing
      those fragments. The fragment atomic charges lie within 1 S.D. of the mean for
      68%, and within 2 S.D. for 91%, of the atoms whose charges were computed for
      whole molecules. The actual charges on any atom are strongly influenced by the
      adjacent connected atoms. There is a large spread of atomic residual charge
      within the fragments database.

PMID- 1403032
TI  - Detection of tumor cells in bone marrow of patients with primary breast cancer: a
      prognostic factor for distant metastasis.
AB  - PURPOSE: At the time of primary surgery, approximately 90% of all patients with
      breast cancer are free of metastases, but in the next 5 years almost 50% of them
      will relapse. We evaluated the significance of the presence of tumor cells in
      bone marrow of patients with primary breast cancer to investigate their
      predictive value for relapse. PATIENTS AND METHODS: Two hundred sixty patients
      with primary breast cancer were examined for tumor cells in bone marrow aspirates
      taken from six sites of the skeleton. After density centrifugation, cells in
      interphase were smeared and stained. For the immunocytologic reaction, we used a
      new monoclonal antibody (2E11) that was reactive with the core protein of the
      tumor-associated glycoprotein TAG12. TAG12 is secreted by nearly all human breast
      carcinomas. RESULTS: A significant correlation was found between tumor-cell
      detection and tumor stage (P < .0001), nodal status (P < .0001), and tumor
      grading (P = .002). A good relation to progesterone receptor (PR; P = .008) was
      found, but there was no correlation to estrogen receptor (ER) and menopausal
      status. Follow-up examinations showed distant metastases in 26 of 211 patients
      (15%). Twenty-two relapses occurred among the 81 patients with 2E11-positive
      cells in bone marrow, but only four occurred among the 130 patients without tumor
      cell detection. CONCLUSIONS: This study suggests that tumor-cell detection in
      bone marrow of patients with primary breast carcinoma is a good predictor for all
      distant relapses (P < .0005, Cox multiple regression analysis) and provides
      additional information in regard to other prognostic factors. The highest
      predicting value for distant metastasis results from the combination of nodal
      status, negative PR, and tumor-cell presence in bone marrow.

PMID- 1403033
TI  - Adjuvant therapy with escalating doses of doxorubicin and cyclophosphamide with
      or without leukocyte alpha-interferon for stage II or III breast cancer.
AB  - PURPOSE: A prospective study in breast cancer patients was undertaken to
      determine whether escalating doses of doxorubicin and cyclophosphamide would
      result in a higher fraction of patients free of disease, and to evaluate the role
      of leukocyte alpha-interferon. PATIENTS AND METHODS: Between 1982 and 1986, 319
      consecutive patients with stage II or III breast cancer with one or more positive
      nodes were assigned randomly to receive adjuvant chemotherapy that consisted of
      escalating doses of doxorubicin and cyclophosphamide in combination with
      vincristine and prednisone or the same chemotherapy regimen followed by 1 year of
      leukocyte alpha-interferon. Doxorubicin was administered by 72-hour continuous
      infusion through a central venous catheter (maximum total cumulative dose, 430
      mg/m2). All patients with positive or unknown estrogen receptor status were also
      given tamoxifen for 1 year. RESULTS: The median follow-up was 71 months (range,
      35 to 99 months). Correlation of disease-free survival (DFS) with dose-intensity
      of cyclophosphamide and doxorubicin showed no improvement in DFS for patients who
      were able to receive escalated drug doses compared with those who were not.
      Doxorubicin administered by continuous infusion was associated with a negligible
      risk of cardiotoxicity in this study despite the administration of higher
      accumulative doses than in our previous adjuvant therapy studies. The DFS rates
      of patients who did and those who did not receive leukocyte alpha-interferon were
      similar. CONCLUSIONS: In this study, there was no real evidence that higher drug
      dose intensity was associated with longer DFS. Leukocyte alpha-interferon as it
      was used in this study had no therapeutic value. Doxorubicin administered by
      infusion was associated with a reduced risk of cardiotoxicity.

PMID- 1403034
TI  - Adjuvant aminoglutethimide for postmenopausal patients with primary breast
      cancer: analysis at 8 years.
AB  - PURPOSE: The study purpose was to evaluate aminoglutethimide (AG) as adjuvant
      therapy in patients with primary node-positive breast cancer in a randomized
      double-blind placebo-controlled trial. PATIENTS AND METHODS: In a multicenter
      trial, 354 postmenopausal women with early breast cancer and histologically
      confirmed positive axillary lymph nodes were randomized after surgery to received
      aminoplac. Patients were prescribed either AG 250 mg four times per day and
      hydrocortisone 20 mg twice per day or placebos of identical appearance for 2
      years. RESULTS: After a median follow-up of 8.1 years, there has been no overall
      benefit for AG in terms of either event-free survival or overall survival (OS).
      However, the results are consistent with interim analyses with a significantly
      improved event-free survival for patients who received AG for up to 4 years,
      although this benefit subsequently disappears. Similarly, there is an improved OS
      for patients who received AG for up to 4 years, but this also subsequently
      disappears. There was a marginal advantage for estrogen receptor (ER)-positive
      patients who received AG (n = 74; P = .054). There was no difference in the sites
      of relapse. There was a significant increase in toxicity for patients who
      received AG. CONCLUSION: The lack of survival benefit with long-term follow-up
      for AG may indicate that aromatase inhibitors have less of an impact on early
      breast cancer than tamoxifen and may imply different biologic mechanisms of
      action.

PMID- 1403035
TI  - Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated
      with cisplatin-based multimodality therapy.
AB  - PURPOSE: At the end of the 1970s it was thought that advanced epithelial ovarian
      cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin
      based combination chemotherapy, and radiotherapy (RT). Such multimodality
      treatment was used as standard therapy at our institution. Our long-term results
      are reviewed. PATIENTS AND METHODS: One hundred ninety-five previously untreated
      patients with stage III or IV EOC were treated between April 1979 and December
      1982. All patients were to have debulking surgery, when feasible, followed by the
      administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a
      total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition
      in patients with disease remaining after the chemotherapy. Maintenance
      chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was
      administered to patients who did not have a documented histologic complete
      remission. RESULTS: The 10-year overall and failure-free survivals were 4% and
      8%, respectively. The median overall survival was 2 years. The achievement of a
      histologic complete response (n = 32) did not equate to cure because 20 (63%) of
      the patients eventually relapsed. Multivariate analysis identified residual
      disease of greater or less than 2 cm as the only independent prognostic factor.
      CONCLUSIONS: Our multimodality treatment program was noncurative for the majority
      of the patients. Innovative therapies are needed before we can hope to cure such
      disease.

PMID- 1403036
TI  - High-dose busulfan in patients with myeloma.
AB  - PURPOSE: To evaluate the use of high-dose busulfan (HDB) with autologous bone
      marrow transplantation (ABMT) in patients with myeloma. PATIENTS AND METHODS:
      Fifteen patients received HDB (16 mg/kg), eight of whom received high-dose
      melphalan (HDM) but had experienced a short remission or progression-free
      interval. Two patients had received HDM on two previous occasions, one had no
      response to low-dose melphalan, and four had impaired renal function (edathamil
      clearance < 40 mL/min). All patients received induction chemotherapy before HDB.
      RESULTS: Two patients were in complete remission (CR) after induction
      chemotherapy before HDB. Of the remaining 13 patients, four (31%) achieved CR and
      two (15%) achieved a partial remission for an overall response rate of 46%. There
      were three treatment-related deaths, but the toxicity was otherwise predictable
      and manageable. CONCLUSIONS: In heavily pretreated patients, HDB results in a
      relatively high response rate. It can also be used safely in patients with renal
      impairment who are not suitable for HDM.

PMID- 1403037
TI  - Phase II trial of cisplatin and alpha-interferon in advanced malignant melanoma.
AB  - PURPOSE: To evaluate the antitumor activity of combination cisplatin (CDDP) and
      alpha-interferon (alpha-IFN) in advanced, measurable metastatic melanoma.
      PATIENTS AND METHODS: Adult patients with metastatic melanoma were required to
      have bidimensionally measurable lesions and a Karnofsky performance status > or =
      60%. Serum creatinine < or = to 1.5 mg/dL, creatinine clearance > or = 60 mL/min,
      adequate organ and bone marrow function, and radiologic proof of the absence of
      brain metastases were required. CDDP 40 mg/m2 intravenously (IV) on day 1 and day
      8, and alpha-IFN 3 million units/m2 subcutaneously on days 1 to 5 and 8 to 12
      were administered every 3 to 4 weeks. RESULTS: Forty-two patients were entered
      onto this phase II trial and were assessable for response and toxicity. Three
      patients achieved complete responses (CRs) that lasted 31+, 5, and 8+ months.
      Seven patients had partial responses (PRs) and a median response duration of 4.4
      months. The overall objective response rate was 24% (95% confidence interval, 12%
      to 39%). Toxicities were mild. Only 11% of the courses required dose reduction of
      alpha-IFN, and three of 128 courses required CDDP dose reduction for reversible
      nephrotoxicity. CONCLUSION: The combination of moderate-dose CDDP and alpha-IFN
      as administered in this schedule is well tolerated and possesses encouraging
      activity in metastatic melanoma.

PMID- 1403038
TI  - A comparison of two short intensive adjuvant chemotherapy regimens in operable
      osteosarcoma of limbs in children and young adults: the first study of the
      European Osteosarcoma Intergroup.
AB  - PURPOSE: A randomized pilot study was undertaken to assess the acute and chronic
      toxicities of two short intensive chemotherapy regimens, and to evaluate the
      feasibility of conservative surgery in this setting. Additional aims were to
      determine the clinical and radiologic response and the degree of histologic
      necrosis after chemotherapy. With extension of the study, eventual accrual was
      sufficient to compare disease-free survival (DFS) and overall survival (OS).
      PATIENTS AND METHODS: Between July 1983 and December 1986, the European
      Osteosarcoma Intergroup (EOI) entered 198 eligible patients with classic high
      grade extremity osteosarcoma onto a randomized trial that compared doxorubicin
      (DOX) 25 mg/m2/d times three, intravenous (IV) bolus plus cisplatin (CDDP) 100
      mg/m2, 24 hour infusion, every 3 weeks times six; the same combination was
      preceded 10 days earlier by high-dose methotrexate (HDMTX) 8 g/m2, 6-hour
      infusion, every 4.5 weeks times four. In the majority of patients (179),
      chemotherapy was commenced after biopsy; definitive surgery was scheduled at 9
      weeks in both groups. RESULTS: Toxicities for both regimens did not differ
      substantially from those that occurred in other trials of adjuvant chemotherapy
      in osteosarcoma. Local recurrence (9%) and surgical complications (18%) after
      conservative surgery were acceptable. With a median follow-up of 53 months, DFS
      at 5 years is superior (P = .02) for DOX/CDDP, 57% versus 41%, although OS, 64%
      versus 50%, is not different significantly (P = .10). In a subset of 66 patients
      for whom pathologic data on the resected specimen were available, DFS (P = .003)
      and OS (P = .008) were better for those who demonstrated > or = 90% necrosis.
      CONCLUSION: A brief intensive chemotherapy regimen of DOX/CDDP has produced
      excellent long-term results, which are similar to those that have been achieved
      in cooperative group studies of longer, more complex multiagent chemotherapy, and
      provide the basis for a direct comparison in the next EOI study.

PMID- 1403039
TI  - Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric
      Oncology phase II study.
AB  - PURPOSE: A phase II study of etoposide (VP 16) and carboplatin (CBDCA) was
      performed in patients with metastatic neuroblastoma (NB). The aim of the study
      was to find an alternative treatment for induction with different toxicities than
      the VP 16/cisplatin (CDDP) combination. PATIENTS AND METHODS: Forty-seven
      patients who were from 6 months to 16 years of age, with either relapsed (29) or
      primary resistant (18) NB, were included in a cooperative multicenter phase II
      study of the French Society of Pediatric Oncology (SFOP). The schedule consisted
      of 5 consecutive days of VP 16 100 mg/m2/d and CBDCA 160 mg/m2/d. RESULTS: The
      response rate for the 39 assessable patients was 43%; there were four complete
      remissions and 13 partial remissions. Neither the status of the patients nor the
      total dose of CDDP that was received previously influenced response. Hematologic
      toxicity was marked and caused considerable delay between courses (median
      interval, 39 days). In these heavily pretreated patients, 16% had a more than 50%
      decrease in creatinine clearance and a 22% World Health Organization (WHO) grade
      2 ototoxicity. CONCLUSION: This VP 16/CBDCA combination deserves further
      evaluation for efficacy and toxicity in newly diagnosed patients, and the
      combination of both drugs should be considered for high-dose therapy with bone
      marrow transplantation.

PMID- 1403040
TI  - Phase I trial of etoposide with cyclosporine as a modulator of multidrug
      resistance.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) of cyclosporine (CsA)
      infusion administered with etoposide for 3 days in patients with cancer. PATIENTS
      AND METHODS: Of the 72 registered patients, 26 were treated initially with CsA
      and etoposide. Forty-six received etoposide alone until disease progression, and
      31 of these proceeded to CsA and etoposide. CsA was administered as a 2-hour
      loading dose (LD) and as a 3-day continuous infusion (CI); doses were escalated
      from 2 to 8 mg/kg LD and 5 to 24 mg/kg/d CI. RESULTS: Fifty-seven patients were
      treated with 113 cycles of CsA with etoposide. Steady-state serum CsA levels
      (nonspecific immunoassay) more than 2,000 ng/mL were achieved in 91% of the
      cycles at CsA doses > or = 5 mg/kg LD and > or = 15 mg/kg/d CI. The major dose
      related toxicity of CsA was reversible hyperbilirubinemia, which occurred in 78%
      of the courses with CsA levels > 2,000 ng/mL. Myelosuppression and nausea were
      more severe with CsA and etoposide. Other CsA toxicities included hypomagnesemia,
      60%; hypertension, 29%; and headache, 21%. Nephrotoxicity was mild in 12% and
      severe in 2% of the cycles. Tumor regressions occurred in four patients after the
      addition of CsA (one non-Hodgkin's lymphoma, one Hodgkin's disease, and two
      ovarian carcinomas). Biopsy procedures for tumors from three of the four patients
      who responded were performed, and the results were positive for mdr1 expression.
      CONCLUSIONS: Serum CsA levels of up to 4 mumol/L (4,800 ng/mL) are achievable
      during a short-term administration with acceptable toxicities when administered
      in combination with etoposide. The CsA dose that is recommended in adults is a LD
      of 5 to 6 mg/kg, followed by a CI of 15 to 18 mg/kg/d for 60 hours. CsA blood
      levels should be monitored and the doses should be adjusted to achieve CsA levels
      of 2.5 to 4 mumol/L (3,000 to 4,800 ng/mL). Reversible hyperbilirubinemia may be
      a useful marker of inhibition by CsA of P-glycoprotein function. When used with
      high-dose CsA, etoposide doses should be reduced by approximately 50% to
      compensate for the pharmacokinetic effects of CsA on etoposide (Lum et al, J Clin
      Oncol, 10:1635-1642, 1992).

PMID- 1403041
TI  - Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in
      a phase I trial to modulate multidrug resistance.
AB  - PURPOSE: To determine the effects of high-dose cyclosporine (CsA) infusion on the
      pharmacokinetics of etoposide in patients with cancer. PATIENTS AND METHODS:
      Sixteen patients were administered 20 paired courses of etoposide and
      CsA/etoposide. Etoposide was administered daily for three days, alone or with
      CsA, which was delivered by a loading dose and 3-day infusion. Etoposide was
      measured by high-performance liquid chromatography (HPLC) and serum CsA by
      nonspecific immunoassay. Etoposide pharmacokinetics included area under the
      concentration-time curve (AUC), total and renal clearance (CL), half-life (T1/2),
      and volume of distribution at steady state (Vss). RESULTS: CsA concentrations
      more than 2,000 ng/mL produced an increase in etoposide AUC of 80% (P less than
      .001), a 38% decrease in total CL (P < .01), a > twofold increase in T1/2 (P <
      .01), and a 46% larger Vss (P = .01) compared with etoposide alone. CsA levels
      ranged from 297 to 5,073 ng/mL. Higher CsA levels (< 2,000 ng/mL v > 2,000 ng/mL)
      resulted in greater changes in etoposide kinetics: Vss (1.4% v 46%) and T1/2 (40%
      v 108%). CsA produced a 38% decrease in renal and a 52% decrease in nonrenal CL
      of etoposide. Etoposide with CsA levels > 2,000 ng/mL produced a lower WBC count
      nadir (900/mm3 v 1,600/mm3) compared with baseline etoposide cycles. CONCLUSIONS:
      High-dose CsA produces significant increases in etoposide systemic exposure and
      leukopenia. These pharmacokinetic changes are consistent with inhibition by CsA
      of the multidrug transporter P-glycoprotein in normal tissues. Etoposide doses
      should be reduced by 50% when used with high-dose CsA in patients with normal
      renal and liver function. Alterations in the disposition of other multidrug
      resistance (MDR)-related drugs should be expected to occur with modulation of P
      glycoprotein function in clinical trials.

PMID- 1403042
TI  - Intravenous administration of recombinant human macrophage colony-stimulating
      factor to patients with metastatic cancer: a phase I study.
AB  - PURPOSE: Recombinant human macrophage colony-stimulating factor (M-CSF) has been
      shown to stimulate specifically macrophage lineage differentiation in vitro and
      to induce cells capable of antitumor activity alone or in combination with an
      antibody. The administration of M-CSF to mice has demonstrated antitumor
      therapeutic effects in vivo. Therefore, a phase I trial of M-CSF administration
      to patients with metastatic cancer was undertaken. PATIENTS AND METHODS: M-CSF
      was given by intermittent intravenous bolus infusion every 8 hours for 7 days;
      the treatment cycle was repeated once after a week of rest. Cohorts of three
      patients underwent dose escalation from 10 to 100,000 micrograms/m2/d; 23
      patients received 27 courses of M-CSF administration. All patients had metastatic
      solid tumors refractory to conventional therapy, including renal cell carcinoma
      (RCC) (nine), melanoma (seven), and colorectal carcinoma (seven). RESULTS:
      Treatment-related toxicity was minimal; five patients developed transient signs
      of ocular or periorbital inflammation, with iridocyclitis as the most severe
      manifestation. At the highest doses, platelet counts decreased with therapy (but
      remained > 100,000/mm3) and the absolute monocyte count increased during the
      course of therapy. Only at 30,000 and 100,000 micrograms/m2/d was treatment
      limited because of toxicity (iritis and malaise). Pharmacokinetic studies
      demonstrated up to a 1,000-fold increase in circulating serum M-CSF after bolus
      infusion; half-life varied from 1 to 6 hours. Complete regression of mediastinal
      adenopathy and multiple pulmonary metastases were observed in one patient with
      RCC. CONCLUSION: Recombinant M-CSF can be administered safely to patients with
      metastatic cancer at doses that demonstrate biologic activity.

PMID- 1403043
TI  - AIDS and non-Hodgkin's lymphoma: a pre-pre-B-cell monoclonal lymphoma versus a
      novel mechanism of polyclonality?

PMID- 1403044
TI  - Smoking in young men with testicular cancer.

PMID- 1403045
TI  - Review of autologous bone marrow transplantation for metastatic breast cancer: a
      minor point?

PMID- 1403046
TI  - High-dose chemotherapy with ABMT for metastatic breast cancer.

PMID- 1403047
TI  - All-trans-retinoic acid: what is it good for?

PMID- 1403048
TI  - Radiation-associated breast cancer after Hodgkin's disease: risks and screening
      in perspective.

PMID- 1403049
TI  - Phase I and pharmacokinetic evaluation of all-trans-retinoic acid in pediatric
      patients with cancer.
AB  - PURPOSE: Recent reports of the dramatic antitumor effect of all-trans-retinoic
      acid (RA) in patients with acute promyelocytic leukemia (APL) have renewed
      interest in the oncologic indications for retinoids. Furthermore, a variety of
      pediatric tumors are responsive to RA in vitro, which provides additional
      rationale for a phase I evaluation of RA in children with cancer that is
      refractory to standard therapy. PATIENTS AND METHODS: A phase I trial of RA
      administered orally twice daily for 28-day treatment courses was performed.
      Cohorts of at least three pediatric cancer patients were entered at successive RA
      dose levels (from 45 to 80 mg/m2/d) until dose-limiting toxicity (DLT) was
      consistently observed. RESULTS: The maximum-tolerated dose (MTD) of RA was 60
      mg/m2/d. Three of eight patients at the 80-mg/m2/d dose level developed
      reversible pseudotumor cerebri that necessitated discontinuation of the agent.
      Both patients with APL achieved complete remission (CR), whereas no patients with
      solid tumors had objective responses. Pharmacokinetic studies demonstrated a
      relatively short terminal half-life for RA (45 minutes), with diminution in
      plasma levels after chronic dosing. CONCLUSIONS: The MTD and recommended phase II
      dose for RA in children is 60 mg/m2/d given twice daily. Reversible CNS toxicity
      related to RA-induced pseudotumor cerebri is dose-limiting. Two children with APL
      achieved a CR to RA, which supports the inclusion of pediatric patients in
      clinical trials that evaluate the use of RA for patients with APL.

PMID- 1403050
TI  - Breast cancer in patients irradiated for Hodgkin's disease: a clinical and
      pathologic analysis of 45 events in 37 patients.
AB  - PURPOSE: To characterize the clinical and pathologic features of patients who
      developed breast cancer (BC) after treatment for Hodgkin's disease (HD). Recent
      epidemiologic studies have shown that women who are cured of HD have an increased
      risk of developing BC. PATIENTS AND METHODS: The clinical data, mammograms, and
      pathologic specimens of 37 women who developed 45 BCs (eight bilateral events),
      and had a prior history of treatment for HD were analyzed. RESULTS: The median
      age at diagnosis of HD was 27 years (range, 11 to 60). All patients received
      radiotherapy (RT) to the upper part of their body, and 10 also had chemotherapy
      for HD. The median interval from the treatment of HD to the diagnosis of BC was
      15 years (range, 8 to 34). The median age at diagnosis of BC was 43 years (range,
      27 to 75), 41% of patients were 39 years old or younger. Most mammograms (81%)
      showed abnormal findings of mass and/or microcalcifications. Of the eight
      patients (22%) with bilateral tumors, four were synchronous and four were
      metachronous. Involvement of the medial half of the breast occurred more
      frequently than in patients with primary BC (39% and 21%, respectively; P <
      .002). But, the histologic types, grades, presence of lymphocytic reaction, and
      lymphatic invasion were similar to those observed in 935 primary BC patients who
      were previously analyzed at our center. The 6-year actuarial relapse-free
      survival (RFS) for node-negative BC after HD was 85%. Node-positive patients had
      a significantly lower RFS of 33% (P = .002). CONCLUSIONS: In comparison to
      patients with primary BC, patients who develop BC after HD are more likely to be
      younger, have bilateral disease, and have their tumors more frequently involve
      the medial half of the breast. Pathologic characteristics, nodal involvement, and
      prognosis are similar to those of primary BC. BC in women who were treated for HD
      is becoming an increasing problem, as more patients cured of HD reach a follow-up
      time of 10 to 15 years. Breast examination and mammography at an early age should
      be part of the follow-up program for women who are cured of HD.

PMID- 1403051
TI  - High-dose carmustine, etoposide, and cisplatin and autologous bone marrow
      transplantation for relapsed and refractory lymphoma.
AB  - PURPOSE: We determined the toxicity and efficacy of a new preparative autologous
      bone marrow transplantation (ABMT) regimen in patients with relapsed or
      refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS:
      Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63
      years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2,
      etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty
      nine patients also received 15 to 20 Gy local radiation (involved-field
      radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS:
      Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss,
      stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two
      patients died within 40 days of marrow infusion as a result of sepsis and one
      patient died 7 months after transplant as a result of pulmonary fibrosis.
      Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non
      Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained
      alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease)
      at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS:
      This regimen seems to be effective for relapsed lymphoma patients whose disease
      continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free).
      Furthermore, this regimen seems to be effective in patients who have never
      attained a CR (seven of 19 [37%] disease-free).

PMID- 1403052
TI  - Autologous versus allogeneic bone marrow transplantation for non-Hodgkin's
      lymphoma: a case-controlled analysis of the European Bone Marrow Transplant Group
      Registry data.
AB  - PURPOSE: A case-controlled study of patients who reported to the European Bone
      Marrow Transplant Group (EBMTG) was performed to investigate the relative roles
      and efficacy of allogeneic (alloBMT) and autologous bone marrow transplantation
      (ABMT) in non-Hodgkin's lymphoma. PATIENTS AND METHODS: Of 1,060 patients who
      reported to the lymphoma registry, 938 patients underwent ABMT and 122 patients
      underwent alloBMT. A case-controlled study was performed by matching 101 alloBMT
      patients with 101 ABMT patients. The case matching was performed after the
      selection of the main prognostic factors for progression-free survival by a
      multivariate analysis. RESULTS: The progression-free survival was similar in both
      types of transplants (49% alloBMT v 46% ABMT). The overall relapse and
      progression rate for the alloBMT patients was 23% compared with 38% in the ABMT
      patients. This difference was not significant statistically. In the lymphoblastic
      lymphoma subgroup, alloBMT was associated with a lower relapse rate than ABMT
      (24% alloBMT v 48% ABMT; P = .035). The progression-free survival, however, was
      not significantly different because patients with lymphoblastic lymphoma who
      underwent alloBMT had a higher procedure-related mortality (24% alloBMT v 10%
      ABMT; P = .06). A significantly lower relapse/progression rate was also observed
      in patients with chronic graft-versus-host disease (cGVHD) compared with those
      patients without (0% cGVHD v 35% no cGVHD; P = .02). Fourteen of 18 patients who
      had cGVHD also had lymphoblastic lymphoma. CONCLUSION: This study suggests that
      ABMT and alloBMT for non-Hodgkin's lymphoma are comparable, with the exception of
      lymphoblastic lymphoma in which a graft-versus-lymphoma effect may account for
      the lower relapse rate for patients who underwent alloBMT.

PMID- 1403053
TI  - Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37
      antibody in B-cell lymphoma.
AB  - PURPOSE: This study was undertaken to evaluate the tumor targeting, toxicity, and
      therapeutic potential of the anti-B-cell-reactive monoclonal antibody MB-1 (anti
      CD37) labeled with iodine 131 given in a nonmarrow ablative dose range in B-cell
      lymphoma patients who relapsed after chemotherapy. PATIENTS AND METHODS: Twelve
      patients with MB-1-reactive tumors were infused first with 40 mg of trace-labeled
      (3 to 7 mCi) MB-1. Ten patients who had no serious toxicity postinfusion and who
      had successful tumor imaging on serial gamma scans then received at least one 40
      mg radioimmunotherapy (RIT) dose (25 to 161 mCi). Tracer estimates of delivered
      whole-body dose (WBD) were used in prescribing a millicurie RIT dose for seven
      patients. RESULTS: Eleven patients had positive tumor imaging after a tracer
      dose, including patients with bulky tumors and/or large tumor burdens (> or = 1
      kg) +/- splenomegaly. However, overall sensitivity for the detection of known
      tumor sites was only 39%. In six of eight patients with dose-assessable tumors,
      the radiation dose to at least one tumor was 1.1 to 3.1 times higher than to any
      normal organ, excluding the spleen for a 40-mg tracer dose. Tracer-dose
      toxicities included reversible glossal edema in one patient, grade 3 hepatic
      transaminasemia in another, and early drops in both circulating B and T cells
      (with decreases in B cells more pronounced) in nearly all patients. RIT toxicity
      was primarily myelosuppression (especially thrombocytopenia), which had a delayed
      onset and protracted recovery (without significant recovery until at least 2
      months post-RIT). Grade 3 myelosuppression in two of two patients who were
      treated at a tracer-projected 50-cGy WBD level (133 and 149 mCi) precluded
      further planned RIT dose escalation. Less myelosuppression was generally observed
      in patients who were treated at < or = 40-cGy WBD levels. Antimouse antibodies
      developed in two patients. Six patients had tumor responses post-RIT. Four had
      responses that lasted more than 1 month (2 to 6 months), which included one
      complete response, one partial response, one minor response, and one mixed
      response. Responses seemed to occur more frequently in imaged tumors than in
      nonimaged tumors. The most durable response occurred in a patient who had the
      best antibody targeting to tumor. CONCLUSIONS: Although 131I-MB-1 has limited
      diagnostic value, it can produce tumor responses at nonmarrow ablative RIT doses.
      Further studies that focus on improving tumor targeting with this or other B-cell
      reactive radiolabeled antibodies and on ameliorating the myelosuppression
      associated with the RIT-dosing approach used in this trial are warranted.

PMID- 1403055
TI  - Allogeneic marrow transplantation during untreated first relapse of acute myeloid
      leukemia.
AB  - PURPOSE: The purpose of this report was to review the Seattle experience in bone
      marrow transplantation (BMT) for acute myeloid leukemia (AML) during untreated
      first relapse. PATIENTS AND METHODS: Through 1990, 126 patients were transplanted
      during untreated first relapse of AML. Several preparative regimens were used,
      two of which involved more than 20 patients. Regimen 1 (29 patients) consisted of
      cyclophosphamide (CY) 120 mg/kg and 15.75 Gy of fractionated total-body
      irradiation (TBI) with methotrexate (MTX) given intermittently during a 102-day
      period to prevent graft-versus-host disease (GVHD). Regimen 2 (22 patients)
      consisted of the same CY and TBI treatment and a combination of MTX and
      cyclosporine (CSP) for GVHD prophylaxis. The remaining 75 patients were treated
      with 17 other transplant regimens. Outcome was compared for patients who were
      treated with regimen 1, regimen 2, and any other regimen. RESULTS: The 5-year
      probabilities of relapse-free survival (RFS), relapse, and nonrelapse mortality
      for 126 patients were .23, .57, and .44, respectively. With regimen 1, relapse
      (.26) was significantly less than for regimen 2 (.70; P = .004) or any other
      regimen (.76; P = .004). Regimen 1 patients developed more acute GVHD (.67) than
      regimen 2 patients (.26; P = .02) or patients on other regimens (.41; P = .02),
      and had increased nonrelapse mortality. Nevertheless, regimen 1 patients had a
      significantly higher 3-year RFS (.38) than those treated with regimen 2 (.18; P =
      .04) or any other regimen (.20; P = .05). CONCLUSIONS: For patients who received
      120 mg/kg CY and 15.75 Gy TBI, relapse incidence was less and survival was better
      after GVHD prophylaxis with MTX alone than after a combination of MTX and CSP,
      despite a significantly higher incidence of acute GVHD. The results of treatment
      with regimen 1 justify future studies of the optimal timing of allogeneic BMT in
      the treatment of patients with AML.

PMID- 1403054
TI  - Phase I and II study of high-dose ifosfamide, carboplatin, and etoposide with
      autologous bone marrow rescue in lymphomas and solid tumors.
AB  - PURPOSE: High-dose chemotherapy produces durable disease-free remissions in a
      minority of patients with resistant lymphomas and solid tumors. In an attempt to
      improve on the available regimens, ifosfamide, carboplatin, and etoposide (ICE)
      were selected for a new high-dose regimen because of their favorable spectrum of
      nonhematopoietic toxicity and evidence of synergy in in vitro systems. PATIENTS
      AND METHODS: Forty-one patients with drug-resistant Hodgkin's and non-Hodgkin's
      lymphomas, and breast and testicular cancers were entered onto a phase I and II
      trial of a single course of ICE with autologous bone marrow rescue. Before
      transplantation, all patients received combination chemotherapy until maximal
      tumor response was achieved. RESULTS: Patients received total doses of ifosfamide
      from 10 to 18 g/m2, carboplatin from 0.9 to 1.98 g/m2, and etoposide from 0.6 to
      1.5 g/m2 administered during a 4-day period, with a maximum-tolerated dose (MTD)
      of ifosfamide 16 g/m2, carboplatin 1.8 g/m2, and etoposide 1.5 g/m2. The dose
      limiting toxicities included irreversible renal, cardiac, and CNS dysfunction.
      There were three toxic deaths (7%), and all occurred above the MTD. Thirteen
      patients who were treated at the MTD tolerated the regimen well; reversible renal
      dysfunction and grade 2 mucositis commonly were observed. Of 23 heavily
      pretreated patients with persistent disease at the time of transplant, 10 (43%)
      achieved complete remissions (CRs) and 11 (48%) achieved partial remissions
      (PRs). Hodgkin's and non-Hodgkin's lymphoma patients who were treated at or below
      the MTD had a median potential follow-up of 11.9 months, and 12-month progression
      free survivals of 62% and 48%, respectively. CONCLUSION: High-dose ICE with bone
      marrow rescue was well tolerated with a high response rate, and should be
      considered for further testing.

PMID- 1403056
TI  - Ifosfamide plus etoposide in newly diagnosed Ewing's sarcoma of bone.
AB  - PURPOSE: We assessed the activity of ifosfamide plus etoposide against newly
      diagnosed Ewing's sarcoma of bone by administering this drug pair before standard
      induction therapy (the upfront window approach). PATIENTS AND METHODS: Twenty-six
      children and adolescents with newly diagnosed, previously untreated Ewing's
      sarcoma of bone were enrolled onto this pilot study (EW-87). Eighteen were at a
      higher risk of treatment failure, with a primary tumor size of more than 8 cm or
      metastases at diagnosis. Window therapy with ifosfamide (1.6 g/m2/d with mesna
      uroprotection) and etoposide (100 mg/m2/d) was given in three 5-day cycles at 21
      day intervals. Responses were evaluated clinically and radiologically. Subsequent
      induction therapy comprised three cycles of cyclophosphamide and doxorubicin.
      Radiation therapy was the primary local control modality; surgery was limited to
      biopsy or resection of expendable bones. After the local control phase,
      alternating courses of vincristine plus dactinomycin, ifosfamide plus etoposide,
      and cyclophosphamide plus doxorubicin were given as maintenance therapy. RESULTS:
      There were four complete responses and 21 partial responses to
      ifosfamide/etoposide window therapy (overall response rate 96%; 95% confidence
      interval [CI], 80% to 99%). Disease progression was observed in four patients
      during the cyclophosphamide/doxorubicin phase. Chemotherapy was well tolerated;
      only 16% (20 of 125) of all ifosfamide/etoposide window and maintenance cycles
      resulted in hospitalization for fever and neutropenia. Two patients developed
      chemotherapy-induced cystitis. CONCLUSIONS: The combination of ifosfamide and
      etoposide is highly active against previously untreated Ewing's sarcoma and
      generally is well tolerated. The ultimate impact of these two agents on outcome
      will be determined in randomized multicenter studies.

PMID- 1403057
TI  - Medical Research Council prospective study of surveillance for stage I testicular
      teratoma. Medical Research Council Testicular Tumors Working Party.
AB  - PURPOSE: A prospective study of surveillance after orchidectomy alone in patients
      with stage I nonseminomatous germ cell testicular tumor (NSGCT) was performed to
      determine the relapse-free rate and to identify the histologic criteria that
      predict for relapse. PATIENTS AND METHODS: Three hundred ninety-six patients from
      16 United Kingdom and one Norwegian centers were entered onto the study between
      January 1, 1984 and October 1, 1987 of whom 373 were eligible for analysis. In a
      previous retrospective study, we defined a prognostic index based on histologic
      criteria that identified a group of patients with a high risk of relapse. This
      index was based on the presence of venous and lymphatic invasion,
      undifferentiated cells, and the absence of yolk sac elements in the primary
      tumor. RESULTS: The 2-year actuarial relapse-free rate after orchidectomy was 75%
      (95% confidence interval, 71% to 79%), and the rate at 5 years was 73%. Five
      patients died of tumor or treatment-related complications, which resulted in a 5
      year survival of 98%. The relapse-free rate in patients with three or four risk
      factors was 54%. CONCLUSIONS: This study confirms the safety of surveillance as a
      method of management and identifies a group of patients with a high risk of
      relapse. A prospective phase II study has been initiated to determine whether two
      courses of platinum-based adjuvant chemotherapy will prevent relapse in these
      high-risk patients.

PMID- 1403058
TI  - Consolidation hemibody radiotherapy following induction combination chemotherapy
      in high-tumor-burden multiple myeloma.
AB  - PURPOSE: Curative therapy for multiple myeloma continues to be an elusive goal.
      This report discusses the Northern California Oncology Group (NCOG) phase I and
      II trial in high-tumor-burden disease that used a strategy that consisted of
      induction chemotherapy (vincristine, melphalan, cyclophosphamide, and prednisone
      [VMCP]) for eight cycles followed by sequential hemibody radiation therapy (RT)
      and subsequent chemotherapy for an additional eight cycles. PATIENTS AND METHODS:
      Seventy-two previously untreated stage III myeloma patients were entered onto the
      study. Sixty-nine received induction chemotherapy, 40 received induction
      chemotherapy and hemibody RT, and 23 received induction chemotherapy, hemibody
      RT, and consolidative chemotherapy. RESULTS: Twenty-two complete responses (CRs)
      were obtained by induction chemotherapy, with four additional CRs after RT and
      consolidative chemotherapy. Nineteen patients developed grade 4 hematologic
      toxicity primarily after upper hemibody RT. Eight of these developed long
      standing neutropenia or thrombocytopenia. Median survival of the group was 134
      weeks, which was not significantly different from other approaches. CONCLUSIONS:
      Hemibody RT can be combined with chemotherapy as induction therapy and can be
      safely administered in a community setting. However, as administered here no
      survival advantage was demonstrated.

PMID- 1403059
TI  - Suramin: rapid loading and weekly maintenance regimens for cancer patients.
AB  - PURPOSE: Suramin is an anticancer agent with a narrow therapeutic window and a
      terminal half-life of 45 to 55 days. These characteristics make it necessary to
      control accurately the serum concentrations of the drug. Therefore, the aim of
      the present study was to develop a rapid loading regimen, followed by weekly
      administration of suramin to maintain serum concentrations of between 150 and 300
      micrograms/mL for 8 weeks. PATIENTS AND METHODS: Eligible patients were treated
      with five different loading regimens. Initially, weekly maintenance doses were
      estimated manually by the treating physician. Subsequently, computer-assisted
      dosing that used Bayesian pharmacokinetic modeling was used. RESULTS: Thirty
      eight courses of suramin that were administered to 35 patients were studied. The
      optimal loading regimen consisted of a continuous infusion of 600 mg/m2 during a
      24-hour period, which resulted in a mean serum concentration of 319
      micrograms/mL. Potentially toxic concentrations that were observed with shorter
      infusions were avoided. Maintenance treatment, which used the weekly
      administration of suramin during a 6-hour period, seemed to be able to maintain
      mean suramin serum trough concentrations of 150 micrograms/mL, while preventing
      mean peak concentrations of more than 300 micrograms/mL. The use of Bayesian
      pharmacokinetics was superior to manual estimation in tailoring the optimal dose
      to the therapeutic window. CONCLUSIONS: Continuous infusion is the optimal way of
      delivering suramin during the loading phase. To maintain trough levels and peak
      levels within a narrower therapeutic window, suramin will have to be administered
      more frequently than once a week. Bayesian modeling based on individual serum
      levels and population pharmacokinetics allows accurate dosing to maintain suramin
      levels within the therapeutic window.

PMID- 1403060
TI  - Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective
      clinical study.
AB  - PURPOSE: A prospective clinical study was performed to determine the incidence of
      high-dose continuous intravenous infusion fluorouracil (5FU-CIV) cardiotoxicity.
      PATIENTS AND METHODS: Three hundred sixty-seven patients who were given first
      cycle high-dose 5FU-CIV were monitored for cardiac function by clinical
      examination, ECG, and laboratory tests. 5FU-CIV was administered during a 96- or
      120-hour period at doses that ranged from 600 to 1,000 mg/m2/d. Associated drugs
      included cisplatin (56%), mitomycin (12.5%), folinic acid (leucovorin) (7%), and
      others (14%). Thirty-nine patients (10.5%) received 5FU as a single agent.
      RESULTS: 5FU-induced cardiac events occurred in 28 patients (7.6%; 95% confidence
      interval, 4.9% to 10.3%). Nine of them had a history of cardiac disease. Primary
      tumors included head and neck (n = 13), gastrointestinal (n = 6), breast (n = 3),
      and others (n = 6). The mean onset time of cardiac symptoms was 3 days (range, 2
      to 5). Inaugural symptoms included angina pectoris (n = 18), hypotension (n = 6),
      hypertension (n = 5), malaise (n = 4), dyspnea (n = 2), arrhythmia (n = 1), or
      sudden death (n = 1). At 5FU discontinuation, six patients' cardiac symptoms
      returned to baseline, but 21 patients experienced unstable angina (n = 8),
      hypotension/cardiovascular collapse (n = 11), pulmonary edema (n = 1), or sudden
      death (n = 4). The lethality rate was 2.2% (five sudden deaths plus three
      irreversible collapses). ECG showed repolarization changes (ST segment deviation;
      T-wave inversion) in 65% and/or diffuse microvoltage in 22% of the patients who
      presented with cardiac events. Echocardiography showed partial or global
      hypokinesia in nine of the 16 patients who were examined, and one case of
      prolonged akinesia. Cardiac enzymes rarely showed an increase (n = 2). In severe
      but reversible cases, clinical, ECG, and echographic parameters returned to
      baseline status within 48 hours after the drug discontinuation. A fluorine 19
      nuclear magnetic resonance (19F NMR) analysis of urine was performed on 14
      patients; six had cardiac symptoms and eight did not. Fluoroacetate (FAC), a
      known cardiotoxic compound, was detected in all cases. CONCLUSION: In our study,
      the incidence of high-dose 5FU-CVI cardiotoxicity was 7.6%. The hypothesis of a
      toxic cardiomyopathic process requires further confirmation.

PMID- 1403061
TI  - Phase I evaluation of thrice-daily intravenous bolus interleukin-4 in patients
      with refractory malignancy.
AB  - PURPOSE: A phase I dose-escalation trial of recombinant human interleukin-4 (IL
      4) was performed to determine its toxicity, biologic activity, and potential
      antineoplastic effects. PATIENTS AND METHODS: Ten patients with refractory
      malignancies received IL-4 by bolus intravenous injection every 8 hours on days 1
      to 5 and 15 to 19 (maximum, 28 doses) of a 31-day study period. Three patients
      received 10 micrograms/kg per dose and seven received 15 micrograms/kg per dose
      of IL-4. RESULTS: Toxic symptoms noted at the second dose level included nasal
      congestion, diarrhea, nausea and vomiting, fatigue, anorexia, headache, dyspnea,
      and capillary leak syndrome (median weight gain, 6.1%; range, 3.4% to 11.7%).
      Fever or sustained hypotension sufficient to require pressors did not occur.
      Decreases in lymphocyte count and serum bicarbonate, sodium, albumin, fibrinogen
      and immunoglobulin (Ig) levels, and increases in hematocrit, prothrombin
      time/partial thromboplastin time (PT/PTT), soluble CD23, and, occasionally, serum
      creatinine and transaminases occurred. All side effects resolved by day 31.
      Phenotypic analysis of peripheral-blood mononuclear cells (PBMC) showed a
      decrease in the percentage of circulating CD16 and CD14(+) cells. Plasma tumor
      necrosis factor (TNF) and IL-1 beta levels were unaffected, whereas serum C
      reactive protein (CRP) concentrations increased slightly and plasma IL-1 receptor
      antagonist (IL-1RA) levels increased markedly. No tumor responses were observed.
      CONCLUSIONS: We conclude that 10 micrograms/kg per dose of IL-4 is the maximum
      tolerated dose for this schedule, although 15 micrograms/kg per dose can be
      tolerated if more intensive, but still non-intensive care unit level care is
      provided. The results of this study should aid in the design of future phase II
      trials that involve IL-4 alone or phase I studies that combine IL-4 with other
      cytokines such as IL-2.

PMID- 1403062
TI  - Ethical issues in phase I oncology research: a comparison of investigators and
      institutional review board chairpersons.
AB  - PURPOSE: Phase I research trials assess the safety of agents never before
      administered to humans. In the field of oncology, this practice raises several
      important ethical questions. We examined the ethics of these trials by surveying
      phase I oncology investigators and institutional review board (IRB) chairpersons
      at major cancer research centers around the country. METHODS: Questionnaires were
      mailed to 78 investigators and 47 chairpersons to obtain their views on the
      ethical propriety of conducting phase I oncology research, and on institutional
      practice regarding these trials. The response rate was 68% in each group.
      RESULTS: The majority of each group reported that phase I oncology trials face no
      more scrutiny or resistance in their institution's IRB process than other
      research protocols. Nevertheless, IRB chairpersons were more likely than
      investigators to favor special procedural safeguards to protect subjects in phase
      I oncology trials. Nearly all respondents agreed that although actual medical
      benefit was very uncommon, most patients entered for a chance at a therapeutic
      effect. Investigators were more likely than chairpersons to report that patients
      obtained psychologic benefit from participation in phase I trials. CONCLUSION:
      Although individual IRB chairpersons and oncology investigators may have
      important differences of opinion concerning the ethics of phase I trials, these
      disagreements do not represent a widespread area of ethical conflict in clinical
      research.

PMID- 1403063
TI  - Host factors in breast cancer recurrence.

PMID- 1403065
TI  - Peritoneal absorption of cefoperazone in rats.
AB  - The peritoneal absorption of cefoperazone, administered by intraperitoneal (ip)
      perfusion in a large volume (100 mg/40 ml), was investigated in rats. Its
      pharmacokinetics was also studied after ip or intravenous (iv) injection of 100
      mg/kg in two groups of rats. The peritoneal uptake after the two modes of ip
      administration was rapid, peaking in less than 20 minutes and the means of peak
      concentrations were similar. The peak remained high in the group perfused with a
      large volume for at least 4 hours, which was the end of sample collection. In
      addition, the absorption half-life and the fraction (F) reaching systemic
      circulation were calculated and found to be 10.0 +/- 2.5 min and 0.93,
      respectively. A brief distribution phase (t1/2 alpha 8.0 +/- 0.67 minutes)
      appeared only after the iv bolus. Otherwise the decline in serum concentration
      was monoexponential with half-lives of 39.0 +/- 4.0 and 63.6 +/- 7.5 min for the
      iv and ip injected groups, respectively. The stability of cefoperazone in plasma
      was also investigated in this study. It was found to be unstable at physiological
      pH even at -30 degrees C and the samples collected should be buffered in acidic
      media to optimize stability. The degradation process is likely to contribute to
      its elimination kinetics during in vivo administration.

PMID- 1403064
TI  - Cyclophosphamide, cisplatin, and abdominal radiation in advanced ovarian cancer.

PMID- 1403066
TI  - Penetration of ciprofloxacin into human peritoneal tissue following a single oral
      dose of 750 milligrams.
AB  - The penetration of ciprofloxacin into the peritoneal tissue was studied in 10
      patients after a single oral dose of 750 mg given 5.6 hours (mean) before
      elective laparotomy. The mean tissue level was 0.29 micrograms/ml (range, 0.082
      to 0.96 micrograms/ml) while the mean concomitant serum level was 1.3
      micrograms/g (range, 0.52 to 2.57 micrograms/g). The achieved concentrations are
      above the minimum inhibitory concentrations (MICs) of ciprofloxacin for most gram
      negative bacteria commonly involved in intra-abdominal infections.

PMID- 1403067
TI  - "Nonantibiotics"--their relevance in research and potential place in future
      antimicrobial chemotherapy.

PMID- 1403069
TI  - Metastatic squamous cell carcinoma of an unknown primary tumor localized to the
      neck.
AB  - 68 patients with metastatic squamous-cell carcinoma (SCC) of an unknown primary
      tumor localized to the neck were treated between 1981 and 1990. There were 11
      patients treated with radiotherapy alone, 24 patients treated with surgery and
      radiotherapy and 33 patients treated with radiotherapy and chemotherapy. Male to
      female ratio was 1.9:1 and the median age was 55 years (range, 33 to 71 years).
      41 (61%) patients had N3 disease, 18 (26%) patients had N2 disease and 9 (13%)
      patients had N1 disease. The majority of N3 patients were treated with
      radiotherapy + chemotherapy (n = 17) and surgery + radiotherapy (n = 17). The
      complete response (CR) to radiotherapy + chemotherapy was 73% with 19 patients
      having no evidence of disease currently. The median survival time (MST of this
      group was 34+ months. Of the 35 patients who had surgery and/or radiotherapy, 7
      (20%) currently have no evident disease. The MST of these two groups (combined)
      was 22 months. Patients with N3 disease who received radiotherapy + chemotherapy
      had a higher CR rate and longer MST when compared with those without
      chemotherapy.

PMID- 1403068
TI  - Aztreonam versus colistin-neomycin for selective decontamination of the digestive
      tract in patients undergoing bone marrow transplantation: a randomized study.
AB  - Aztreonam (Az), a minimally absorbable monobactam antibiotic, was compared to
      colistin plus neomycin (CN), for intestinal decontamination during Bone Marrow
      Transplantation (BMT) in a controlled study. Thirty-four consecutive patients
      were randomized in two groups and evaluated for number of febrile episodes, days
      of fever, fecal cultures and clinical symptoms related to infections or
      colonizations. No significant differences were observed suggesting that Az is at
      least as effective as the CN regimen and may be considered as an alternative
      approach for intestinal decontamination in BMT patients.

PMID- 1403070
TI  - Salvage chemotherapy in colorectal cancer patients with good performance status
      and young age after failure of 5-fluorouracil/leucovorin combination.
AB  - Forty-one patients with metastatic colorectal cancer were treated every four
      weeks with methotrexate 25 mg/m2 i.v. days 1, 8, 15; vincristine 1 mg/m2 i.v. day
      1; lomustine 100 mg/m2 p.o. day 1. Inclusion criteria were: failure of previous 5
      fluorouracil/leucovorin treatment; performance status (ECOG) 0-2; age less than
      60 years; presence of symptoms; absence of concomitant diseases. Metastatic sites
      were: liver 30, lung 4, abdominal/pelvic mass 7. Three patients achieved partial
      responses (2 liver, 1 lung metastases); 4 showed stable disease and 34 progressed
      on therapy. The median survival of patients with partial response, stable disease
      and progression was comparable (24, 21, 22 weeks respectively). The most common
      toxicity was hematologic (thrombocytopenia and leukopenia). Other side effects
      included nausea and vomiting, stomatitis and diarrhea. Symptoms were not affected
      by treatment. We conclude that salvage chemotherapy is not recommended in
      colorectal cancer after 5-fluorouracil/leucovorin treatment even in patients with
      generally considered favorable characteristics for response to chemotherapy.

PMID- 1403071
TI  - Ewing's sarcoma: experience with 12 cases.
AB  - Twelve patients with localized Ewing's sarcoma were treated between 1980-1990 at
      the Istanbul School of Medicine, Department of Pediatric Oncology-Hematology,
      Oncology Research and Treatment Center and Our Children Leukemia Foundation.
      There were 8 boys and 4 girls, with a mean age of 8.1 (range 3-17) years. The
      tumors were in the femur in 3 patients, in the humerus and rib in 2 patients each
      and in the tibia, radius, vertebra, clavicula and pelvis in 1 patient each.
      Chemotherapy alone was applied in 2 patients, 1 patient had chemotherapy and
      radiotherapy. The remaining 9 cases were treated with Chemotherapy and
      radiotherapy (during the chemotherapy). The chemotherapy protocols were: VAC (n =
      5), VACA (n = 3), IVAD (n = 3) and T.9 (n = 1). One patient died from the disease
      itself. Remissions were achieved in the other 11 patients. After 5 to 95 months
      (mean: 22 months) 7 patients had relapsed (4 had local and 3 had distant
      metastases). Three patients were not able to be followed, 3 died due to
      additional problems (infection, cardiotoxicity). The best prognosis was achieved
      when Ewing's sarcoma initiated in the long bones, with less than 100 ml tumor
      volumes and patients were under 5 years old. There were no significant
      differences among chemotherapy protocols.

PMID- 1403072
TI  - Cyclophosphamide plus vincristine and prednisone in the treatment of severe
      pemphigus vulgaris refractory to conventional therapy.
AB  - Five patients with severe pemphigus vulgaris refractory to conventional therapy
      with azathioprine and corticosteroids were treated with cyclophosphamide,
      vincristine and prednisone. One patient was not evaluable, while the remaining
      four patients showed a complete response. Duration of response was in the range
      of 13-94 months. Toxicity was mainly represented by alopecia, myelosuppression
      and gastrointestinal side-effects such as nausea/vomiting. Although
      cyclophosphamide and vincristine may induce severe side-effects, this association
      may be useful in controlling severe disease resistant to previous conventional
      therapies.

PMID- 1403073
TI  - In vitro assessment of rokitamycin against problem gram-positive cocci.
AB  - Rokitamycin was more active than erythromycin against erythromycin-sensitive
      strains of Staphylococcus aureus and enterococci, but somewhat less active
      against coagulase-negative staphylococci. Strains with inducible resistance to
      erythromycin were uniformly resistant to erythromycin, while rokitamycin was
      active against such strains. Strains with constitutive resistance to erythromycin
      were also uniformly resistant to erythromycin, and most were also resistant to
      rokitamycin. However, 5 of 21 coagulase-negative staphylococci and 2 of 20
      enterococci remained sensitive to rokitamycin. This is a novel finding, perhaps
      suggesting a new mechanism of macrolide resistance.

PMID- 1403074
TI  - High-level aminoglycoside resistance among enterococci: evaluation of an agar
      screen susceptibility test.
AB  - Seventy-five enterococci from infected (63 isolates) and colonized (12 isolates)
      patients hospitalized in various divisions of the Policlinico Umberto I,
      University of Rome, were in vitro studied for high-level resistance (HLR) to
      gentamicin (HLRG) and streptomycin (HLRS) with adoption of a standard broth
      dilution and an agar screen test. The employed procedures provided equal results
      for 100% of the 75 isolates. Of these, 21 (28%) showed HLRG and 43 (57%) HLRS.
      Combined HLRG and HLRS were found in 18 (24%) isolates, whereas HLRS or HLRG
      alone were found in 25 (33%) and 3 (4%) isolates respectively. It is concluded
      that HLR to aminoglycosides may represent a major problem in Italian
      institutions. Along with other established procedures, the agar screen test
      employed in the study may be used to detect this antibiotic resistance in
      enterococci.

PMID- 1403075
TI  - Microbiological considerations of the etiological agents of lower respiratory
      tract infections.
AB  - One hundred eight-four sputum specimens from the same number of patients with
      lower respiratory tract infections were examined to determine the bacterial count
      and the relationship between the microorganisms isolated and the presumptive
      pathology. The sputa were subdivided into three groups; "high probability", "low
      probability", and "contaminated sputa", following the criteria of the microscopic
      readings: sputum with more than 25 white cells and low numbers of squamous
      epithelial cells represents true lower respiratory tract infections (high
      probability); those with fewer than 25 white cells represent non-bacterial
      infections or non-infected sputa (low probability) while sputa with more than 25
      squamous cells per field represent contaminated specimens (contaminated sputa).
      Statistical analysis was carried out to correlate these data. Haemophilus
      influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, and
      Streptococcus pyogenes showed significant differences in the three groups
      considered.

PMID- 1403076
TI  - Pneumonia complicating abdominal sepsis: an experimental model of hematogenous
      contamination of the lung.
AB  - Pulmonary infection complicating intra-abdominal sepsis is a major clinical
      problem. An experimental model for intra-abdominal sepsis was created with
      implantation of gelatin capsules, containing 3 x 10(8) cfu E. coli strain no.
      2554, in the peritoneal cavity of 20 rats (10 animals received and 10 did not
      receive antibiotic therapy with ceftriaxone) in order to verify the role of the
      primary site of infection in the pathogenesis of pneumonia. Ten rats were
      sacrificed to determine the relative pulmonary weight and 10 were submitted to
      simple laparotomy and insertion of a germ-free capsule (sham-operated group). In
      this group of animals there was only one death (10%). All the rats that received
      antibiotic therapy survived until sacrifice while all the rats that did not
      receive ceftriaxone died, 7 within the 2nd and 3 on the 6th postoperative day.
      Pneumonia and peritonitis developed only in the animals that did not receive
      ceftriaxone. Bacteriological findings of material obtained from peritoneal and
      pleural cavities revealed the same strain of E. coli used for the experiment,
      suggesting that bacteria involved in the pleuro-pulmonary infections may
      originate in the primary site of infection and that antibiotic therapy started at
      the moment of contamination, can prevent this major complication.

PMID- 1403077
TI  - Cefuroxime axetil in the treatment of acute otitis media in children.
AB  - Cefuroxime axetil was evaluated for clinical efficacy and tolerance in the
      treatment of acute otitis media in children. Fifty-five children, 5.0 to 10.8
      years, were randomly assigned to receive 250mg cefuroxime axetil every 12 hours
      or 50mg/kg/day amoxicillin in three divided doses. Both treatment schemes lasted
      for 10 days. Acute otitis media was diagnosed by the presence of erythema and/or
      opacity with bulging of the tympanic membrane. A tympanogram was obtained upon
      enrollment to the study, as well as within 2 days after completion of therapy.
      Fifty-one children completed the treatment protocol. The cure rate was 74.1% for
      cefuroxime axetil and 75.0% for amoxicillin. Clinical improvement was noted in
      25.9% of children treated with cefuroxime axetil and in 25.0% of those treated
      with amoxicillin. There was no clinical failure in the two treatment groups. None
      of the children experienced relapse of acute otitis media during the month
      following completion of therapy. The findings indicate that cefuroxime axetil
      given twice daily has comparable efficacy to amoxicillin given three times daily
      in the treatment of children with acute otitis media.

PMID- 1403078
TI  - Subcutaneous nodules caused by Pseudomonas aeruginosa: healing without incision
      and drainage.
AB  - In a patient with multiple myeloma, numerous indurated, subcutaneous nodules and
      pyomyositis due to Pseudomonas aeruginosa were noted. These lesions resolved with
      ciprofloxacin plus ceftazidime therapy without surgical incision and drainage.
      Despite another course of cancer chemotherapy after total disappearance, there
      were no recurrences at the end of 3 months. Quinolones initially combined with
      other antipseudomonal beta-lactam agents may be the drugs of choice in the
      management of patients with subcutaneous nodules caused by P. aeruginosa.

PMID- 1403079
TI  - Effects of endotoxin in mice bearing solid metastasizing tumors and treated with
      lysozyme hydrochloride.
AB  - The effects of the i.v. administration of endotoxin (6.25-50 micrograms/mouse on
      day 13 after tumor implantation) in mice treated orally with lysozyme
      hydrochloride (100 mg/kg on days 5-12 from tumor implantation) were examined
      using Lewis lung carcinoma in the C57Bl mouse and MCa mammary carcinoma of CBA
      mice. On primary tumor growth, endotoxin alone causes a dose-dependent and
      statistically significant reduction with a nadir on day +2 from endotoxin
      treatment. Combined with lysozyme, endotoxin causes an effect independent of the
      dose used, corresponding to the effect caused by endotoxin alone at the dose of
      25 micrograms/mouse. No tumor regression was recorded in any of the treated
      groups. Endotoxin is virtually devoid of effects at the metastatic level. In the
      same conditions, lysozyme causes a reduction of primary tumor growth and a more
      pronounced inhibition of lung metastasis formation as expected from its already
      reported effects. The antitumor activity of endotoxin, unlike lysozyme, can be
      ascribed to tumor hemorrhagic necrosis due to tumor necrosis factor (TNF)
      production, as determined in tumor homogenates. Endotoxin does not increase the
      antitumor effects in mice treated with lysozyme, as expected from the data
      obtained with the more immunogenic SA1 sarcoma, although lysozyme increased the
      mitogenic response to ConA of ex vivo isolated splenocytes, in vitro cultured in
      the presence of IL-2.

PMID- 1403080
TI  - Increased spontaneous cell detachment of F10 cells induced in vitro by some
      calcium-channel blockers.
AB  - We investigated the action of some Ca(++)-channel blockers such as flunarizine,
      nifedipine and verapamil on F10 cells in vitro. Cell adhesion to the growth
      substratum, evaluated by the technique of spontaneous detachment in culture
      medium, is reduced in Ca(++)-channel blocker treated cells by comparison with
      controls. In our opinion such an event could also explain the inhibitory effect
      on cell growth and colony forming ability.

PMID- 1403081
TI  - Chemotherapy with cisplatin, epirubicin, methotrexate in the treatment of locally
      advanced or metastatic transitional cell cancer of the bladder (TCC).
AB  - Forty patients with advanced transitional cell cancer (TCC) of the bladder were
      treated with cisplatin, epirubicin, methotrexate (PEM, every 3-4 weeks). If
      creatinine clearance was reduced to 40 ml/min, the usual full doses of cisplatin
      and methotrexate, 50 mg/m2, were proportionally reduced. 23 patients had full
      dose (FD) therapy, 17 had reduced dose (RD) (40-20 mg/m2). Two patients achieved
      complete response and 17 partial response. The overall response rate was 19/40
      (47.5%), 11/23 (48%) for FD and 8/17 (47%) for RD (p = 1.000). 17/40 pts (42.5%)
      had no-change and 4/40 (10%) had disease progression. The median duration of CR
      and PR was 32 weeks, range 4-82 (22 weeks, range 12-52 for FD; 32 weeks, range 4
      82 for RD, cisplatin p = .7362). The main side effect was vomiting (35/40 pts,
      87.5%, 20/23 = 87% for FD, 15/17 = 90% for RD, p = 1.000). Leukopenia was
      observed in 12 patients (30%, nadir 3,240 range 900-3,800, 6/23 = 26% for FD,
      6/17 = 35% for RD, p = .7285), alopecia in 18 patients (45%, 15/23 = 65% for FD,
      3/17 = 18% for RD, p = .004). The results of this study show that a dose
      escalation to 50 mg/m2 for cisplatin, epirubicin and methotrexate in the PEM
      regimen results in an increase in overall response (OR) (19/40 = 47.5%) with
      respect to a historical control using the same drugs at doses of 40 mg/m2 (12/35
      = 34%). In patients with normal renal function the escalated dose was tolerated
      without a corresponding increase in toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403082
TI  - Chemotherapy in head and neck cancer (I): Management of recurrent or metastatic
      disease.

PMID- 1403083
TI  - Equivalent forgetting rates in long-term memory for diencephalic and medial
      temporal lobe amnesia.
AB  - Amnesia can result from damage to either the midline diencephalon or the medial
      temporal lobe. An important related question has been whether these two forms of
      amnesia result in similar or different kinds of memory impairment. Earlier
      studies raised the possibility that differences might exist in the rate of
      forgetting within long-term memory, specifically, that the forgetting rate is
      normal in diencephalic amnesia but abnormally rapid in medial temporal lobe
      amnesia. In the present study, forgetting was studied in five amnesic patients
      with damage to the medial temporal lobe, six amnesic patients with damage to the
      diencephalon, and 10 normal subjects. One hundred twenty pictures were presented
      to the control subjects for 1 sec each and to the amnesic patients for 8 sec
      each. Retention was then tested after 10 min, 2 hr, and 30-32 hr using four
      different procedures for testing recognition memory. The different exposure times
      for the pictures succeeded in matching the performance scores of both groups of
      amnesic patients and the control subjects at the 10 min retention interval. Both
      groups of amnesic patients also performed similarly to control subjects at
      retention delays of 2 hr and 30-32 hr. In addition, performance was nearly
      identical, regardless whether recognition memory was assessed by asking subjects
      to select the new items or the old items. The findings emphasize the similarities
      between medial temporal lobe and diencephalic amnesia.

PMID- 1403084
TI  - Development of retinal displaced ganglion cells in the chick: neurogenesis and
      morphogenesis.
AB  - The time of birth of displaced ganglion cells (DGCs) was determined by
      autoradiography. DGCs start to leave the cell cycle early, on embryonic day 3, in
      the central and peripheral retina, and end on embryonic day 8, also in both areas
      of the retina. During the period of neurogenesis, unlabeled (born) DGCs do not
      appear distributed in spatial gradients as do the ganglion, amacrine, and other
      cell types in the retina (Prada et al., 1991). Our results show characteristic
      spatial and temporal patterns of DGC neurogenesis, which differ from those of the
      other retinal cell types. The morphogenesis of DGCs was studied by means of Golgi
      preparations. After leaving the cycle, DGC neuroblasts detach from the
      ventricular lining; they then move their soma through the vitreal process toward
      the final position at the same time that they emit the axon. Also during soma
      translocation, a transient sprouting of a few short processes is emitted from the
      vitreal process of the cell, close to where the soma is later located, suggesting
      that the "abnormal" position of DGCs could be specifically marked during the
      process of migration.

PMID- 1403085
TI  - A novel T-type current underlies prolonged Ca(2+)-dependent burst firing in
      GABAergic neurons of rat thalamic reticular nucleus.
AB  - The inhibitory GABAergic projection of thalamic nucleus reticularis (nRt) neurons
      onto thalamocortical relay cells (TCs) is important in generating the normal
      thalamocortical rhythmicity of slow wave sleep, and may be a key element in the
      production of abnormal rhythms associated with absence epilepsy. Both TCs and nRt
      cells can generate prominent Ca(2+)-dependent low-threshold spikes, which evoke
      bursts of Na(+)-dependent fast spikes, and are influential in rhythm generation.
      Substantial differences in the pattern of burst firing in TCs versus nRt neurons
      led us to hypothesize that there are distinct forms of transient Ca2+ current
      (I(T)) underlying burst discharges in these two cell types. Using whole-cell
      voltage-clamp recordings, we analyzed I(T) in acutely isolated TCs and nRt
      neurons and found three key differences in biophysical properties. (1) The
      transient Ca2+ current in nRt neurons inactivated much more slowly than I(T) in
      TCs. This slow current is thus termed I(Ts). (2) The rate of inactivation for
      I(Ts) was nearly voltage independent. (3) Whole-cell I(Ts) amplitude was
      increased when Ba2+ was substituted for Ca2+ as the charge carrier. In addition,
      activation kinetics were slower for I(Ts) and the activation range was
      depolarized compared to that for I(T). Other properties of I(Ts) and I(T) were
      similar, including steady-state inactivation and sensitivities to blockade by
      divalent cations, amiloride, and antiepileptic drugs. Our findings demonstrate
      that subtypes of transient Ca2+ current are present in two different classes of
      thalamic neurons. The properties of I(Ts) lead to generation of long-duration
      calcium-dependent spike bursts in nRt cells. The resultant prolonged periods of
      GABA release onto TCs would play a critical role in maintaining rhythmicity by
      inducing TC hyperpolarization and promoting generation of low-threshold calcium
      spikes within relay nuclei.

PMID- 1403087
TI  - Ectopic expression of ultraviolet-rhodopsins in the blue photoreceptor cells of
      Drosophila: visual physiology and photochemistry of transgenic animals.
AB  - We have generated transgenic flies expressing R7 cell-specific opsins in the
      major class of photoreceptor cells of the Drosophila retina and characterized
      their spectral properties using high-resolution microspectrophotometry and
      sensitivity recordings. We show that the Rh3 and Rh4 opsin genes encode UV
      sensitive opsins with similar spectral properties (lambda max = 345 nm and 375
      nm), and that Rh3 corresponds to the R7p and R7marg class of visual pigments. We
      have also generated Rh3 and Rh4 isoform-specific antibodies and present an R7
      cell map of the Drosophila retina. In a related set of experiments, we show that
      it is possible to coexpress two different visual pigments functionally in the
      same cell and produce photoreceptors that display the summed spectral response of
      the individual pigments. These findings open up the possibility of tuning an
      animal's visual behavior by targeted expression of combinations of opsin genes to
      selective types of photoreceptors.

PMID- 1403086
TI  - A time course for the focal elevation of synthesis of basic fibroblast growth
      factor and one of its high-affinity receptors (flg) following a localized
      cortical brain injury.
AB  - Traumatic injury to the CNS initiates transient and unsuccessful regeneration of
      damaged neural pathways, accompanied by reactive gliosis, angiogenesis, and
      deposition of a dense fibrous glial/meningeal scar at the wound site. Basic
      fibroblast growth factor (basic FGF) is a CNS protein with potent effects on
      neurons, glia, fibroblasts, and vascular endothelial cells. Hybridization and
      immunocytochemical methods were used to examine temporal and spatial changes in
      distribution and levels of basic FGF protein and mRNA and also of its receptor
      mRNA (flg), following a defined wound to the cerebral cortex of adult rat brains.
      In the injured brain, a rapid, transient increase in basic FGF mRNA and protein
      is readily detectable within 7 d of surgery and thereafter declines in the
      tissues bordering the lesion. The increased expression is localized to multiple
      cell types including macrophages, neurons, astrocytes, and vascular endothelial
      cells. The changes in immunoreactive basic FGF parallel changes in the
      bioactivity of extracted heparin-binding proteins, which include basic FGF. Focal
      increases in flg mRNA appear 7 d after injury and subside by 14 d. The changes in
      local basic FGF synthesis, concentration, localization, and bioactivity suggest
      that this growth factor may contribute to the cascade of cellular events that
      occur in CNS wound repair.

PMID- 1403088
TI  - Distributed processing of sensory information in the leech. III. A dynamical
      neural network model of the local bending reflex.
AB  - The subpopulation of identified interneurons in the local bending reflex receive
      multiple inputs from dorsal and ventral mechanoreceptors and have outputs to
      dorsal and ventral motor neurons. Their connections suggest a distributed
      processing mechanism in which withdrawal from dorsal, ventral, or lateral stimuli
      is controlled by a single population of approximately 40 multifunctional
      interneurons, but it is unclear whether additional interneurons dedicated to
      particular inputs are needed to account for each kind of bend. We therefore asked
      whether a model could be constructed that reproduced all behaviors without
      dedicated interneurons. Interneurons in the model were constrained to receive
      both dorsal and ventral inputs. Connection strengths were adjusted by gradient
      descent optimization until the model reproduced the amplitude and time course of
      motor neuron synaptic potentials in intracellular recordings of the response to
      many different stimuli. After optimization, the similarity between model and
      identified interneurons showed that additional dedicated interneurons are not
      necessary to produce all forms of the behavior. Successful optimization of
      networks with many fewer interneurons showed that the 40-interneuron network is
      redundant, raising the possibility that the interneurons have additional
      functions. Finally, optimizing networks with additional constraints produced
      better matches to some of the identified interneurons and showed that local
      bending can be produced by two populations of interneurons: one with outputs
      consistent with dorsal bending, the other with ventral bending. This suggests a
      simple model in which two principal types of interneurons produce many different
      behaviors and predicts the type of interneuron that remains to be identified.

PMID- 1403089
TI  - Olfactory sensory neurons are trophically dependent on the olfactory bulb for
      their prolonged survival.
AB  - In most neural systems, developing neurons are trophically dependent on contact
      with their synaptic target for their survival and for some features of their
      differentiation. However, in the olfactory system, it is unclear whether or not
      the survival and differentiation of olfactory sensory neurons depend on contact
      with the olfactory bulb (normally the sole synaptic target for these neurons). In
      order to address this issue, we examined neuronal life-span and differentiation
      in adult rats subjected to unilateral olfactory bulb ablation at least 1 month
      prior to use. Life-span of a newly generated cohort of olfactory neurons was
      determined by labeling them at their "birth" via the incorporation of 3H
      thymidine. In the absence of the bulb, neurons are continually produced at a
      twofold greater rate. However, the epithelium on the ablated side is thinner,
      indicating that average neuronal life-span must be reduced in the targetless
      epithelium. Indeed, nearly 90% of the labeled neurons disappear from the
      bulbectomized side between 5 d and 2 weeks of neuronal age. Moreover, on electron
      microscopic examination, olfactory axons are degenerating in large numbers on the
      ablated side. Since labeled neurons migrate apically through the width of the
      epithelium during this same period, it appears that most, if not all, neurons on
      the ablated side have a life-span on the order of 2 weeks or less. In contrast,
      there is a more moderate degree of neuronal loss on the unoperated side of the
      same animals during the first 2 weeks after tracer injection, and that occurs
      while the neurons are concentrated in the deeper half of the epithelium,
      suggesting that there is a preexisting population of neurons in the control
      epithelium that does not die during this period. Likewise, degenerating axons are
      much less frequent on the unoperated side. We conclude that life-span is
      significantly shorter for olfactory neurons born in the targetless epithelium and
      that olfactory neurons are trophically dependent on the presence of the bulb for
      their prolonged survival. Neuronal differentiation in the absence of the bulb was
      assessed according to ultrastructural criteria and the pattern of protein
      expression using antisera to the growth associated protein GAP-43 and the
      olfactory marker protein. By both measures, most neurons in the epithelium on the
      bulbectomized side, but not all, are immature.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 1403090
TI  - Differential expression of somatostatin receptor subtypes in brain.
AB  - The tetradecapeptide somatostatin has been implicated as an important regulator
      of neuronal and neuroendocrine function in the CNS. The cellular actions of
      somatostatin are mediated by specific receptors. The genes encoding two different
      somatostatin receptors (SSTRs) have been isolated and characterized, and RNA
      blotting studies have shown that both SSTR1 and SSTR2 are expressed in the brain.
      In order to gain a better understanding of the functions of somatostatin in the
      CNS, the distribution of SSTR1 and SSTR2 mRNAs was determined using the technique
      of in situ hybridization. SSTR1 mRNA was present throughout the mouse brain,
      particularly in the supra- and infragranular layers of the cortex, the amygdala,
      hippocampus, bed nucleus of the stria terminalis, substantia innominata,
      hypothalamus, pretectum, substantia nigra, parabrachial nucleus, and nucleus of
      the solitary tract. SSTR2 mRNA was primarily observed in the infragranular layers
      of the cortex, the amygdala, claustrum, endopiriform nucleus, arcuate and
      paraventricular nuclei of the hypothalamus, and medial habenular nucleus. Several
      regions of the brain reported to contain dense somatostatin-like immunoreactive
      terminal fields and receptor binding sites were devoid of both SSTR1 and SSTR2
      mRNA, suggesting the existence of additional SSTR subtypes.

PMID- 1403091
TI  - Early development of glycine- and GABA-mediated synapses in rat spinal cord.
AB  - Motoneuron responses to the inhibitory amino acids glycine and GABA, and the
      contribution of inhibitory synapses to developing sensorimotor synapses were
      studied in rat spinal cords during the last week in utero. In differentiating
      motoneurons, glycine and GABA induced Cl(-)-dependent membrane depolarizations
      and large decreases in membrane resistance. These responses gradually decreased
      during embryonic development, and at birth they were significantly smaller than
      in embryos. In motoneurons of embryos and neonates, dorsal root stimulation
      produced only depolarizing potentials, some of which reversed at -50 mV membrane
      potential. Reduction of extracellular Cl- concentrations increased the amplitude
      of these potentials, suggesting that they are generated by Cl- current.
      Contribution of Cl(-)-dependent potentials to compound dorsal root-evoked
      potentials was studied by determining the effects of glycine and GABA antagonists
      on them. In motoneurons of embryos at days 16-17 of gestation (D16-D17),
      strychnine or bicuculline blocked dorsal root-evoked potentials. This suppression
      was neither the result of a decrease in neuronal excitability nor the inhibition
      of glutamate receptors. Strychnine-evoked depression was not blocked by atropine,
      indicating that it was not due to disinhibition of muscarinic synapses. By D19,
      strychnine and bicuculline significantly increased dorsal root-evoked potentials
      rather than blocking them. This reversed function did not result from an increase
      in neuronal excitability or changes in the specificity of strychnine and
      bicuculline antagonism. The number of glycine- and GABA-immunoreactive cells
      increased 20% between D17 and D19. The number of immunoreactive cells and fibers
      significantly increased in the motor nuclei and dorsal horn laminae. These
      morphological changes may contribute to establishment of new synaptic contacts on
      motoneurons, thus changing the actions of strychnine and bicuculline on dorsal
      root-evoked potentials.

PMID- 1403092
TI  - Trigeminal ganglion cell processes are spatially ordered prior to the
      differentiation of the vibrissa pad.
AB  - The rodent trigeminal system is characterized by the punctate organization of its
      afferents and neurons that replicate the distribution of mystacial vibrissae and
      sinus hairs on the snout. We have examined the development of topographic
      equivalence between the sensory periphery on the snout and the brainstem
      trigeminal nuclei in rats. Lipophilic tracers Dil (1,1'-dioctodecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate) and DiA [4-(4-dihexadecylaminostyryl)-N
      methylpyridinium iodide] were used to label trigeminal ganglion cells and their
      processes differentially from discrete regions of the presumptive vibrissa field
      in fixed embryos. Our results show that trigeminal ganglion cell processes are
      spatially ordered as they reach their peripheral and central targets on embryonic
      day 12 (E12). Peripheral processes of dorsomedially situated ganglion cells
      course dorsally toward the presumptive vibrissa field, and those of
      ventrolaterally situated ganglion cells project ventrally. On E13, the central
      processes of dorsomedially situated ganglion cells enter the brainstem medially
      whereas those of ventrolaterally situated ganglion cells enter laterally. This
      spatial order of trigeminal ganglion cell processes precedes the emergence of
      vibrissa rows in the periphery and the differentiation of brainstem trigeminal
      nuclei. Thus, the subsequent transfer of the vibrissa-related pattern to the
      brainstem trigeminal nuclei occurs along a preexisting, spatially aligned bridge
      formed by the trigeminal ganglion cells.

PMID- 1403093
TI  - Cek5, a membrane receptor-type tyrosine kinase, is in neurons of the embryonic
      and postnatal avian brain.
AB  - Cek5 is a recently identified receptor-type tyrosine kinase of the Eph subclass
      that is nearly ubiquitously expressed during embryonic development (Pasquale,
      1991). Cek5 is predominantly expressed in the avian CNS throughout development,
      and high levels remain apparent in adult neurons. By means of immunofluorescence
      microscopy and high-resolution immunoelectron microscopy, Cek5 was found to be
      expressed in many regions of the chicken brain at various developmental stages,
      most notably in the hippocampus and cerebellum. The highest concentration of Cek5
      was observed in the molecular layer of the cerebellum, associated within the
      axons of mature granule cells (parallel fibers) and with the cell bodies of
      immature granule cells. In the axons of parallel fibers, Cek5 was concentrated in
      the fasciculated nonsynaptic portions. This localization, together with the
      "adhesion" motifs present in the Cek5 extracellular region suggest that Cek5 may
      interact with other cell surface-associated molecules and be involved in the
      growth, guidance, and/or bundling of certain unmyelinated axonal processes.
      Alternatively (or in addition), Cek5 may represent the receptor for a
      neurotrophic substance, similar to several other neuronal transmembrane tyrosine
      kinases.

PMID- 1403094
TI  - Basic fibroblast growth factor: a potential regulator of proliferation and
      intermediate filament expression in the retina.
AB  - Proliferation of astrocytes, and a concomitant increase of intermediate filaments
      in astrocytes are two fundamental responses of the CNS to injury. We have
      previously identified these two events in the retina's response to detachment of
      the neural retina from the adjoining monolayer of retinal pigmented epithelium.
      In order to analyze the potential role of basic fibroblast growth factor (bFGF)
      in these responses, we studied cellular proliferation and intermediate filament
      protein expression in the retinas of cats and rabbits 4 d and 4 weeks after a
      single intravitreal injection of 1 microgram of bFGF. Our results show that bFGF
      stimulates both of these processes in an otherwise normal eye. The eyes that
      received bFGF had significantly elevated numbers of 3H-thymidine-labeled Muller
      cells, astrocytes, vascular cells, retinal pigmented epithelial cells, microglia,
      and macrophages by comparison to control eyes. This proliferation was apparent at
      4 d after the injection of bFGF but not after 4 weeks. In control eyes,
      antibodies to glial fibrillary acidic protein and vimentin labeled intermediate
      filaments only in the inner (vitread) portion of the Muller cells, the
      specialized radial astrocytes that span the width of the retina. In eyes that had
      been injected with bFGF, almost the entire Muller cell cytoplasm was labeled at 4
      d after injection; after 4 weeks, the cytoplasmic labeling intensity had
      increased significantly. Release or activation of endogenous stores of bFGF after
      injury or disease may be involved in the control of cellular proliferation and
      intermediate filament expression in the retina and elsewhere in the CNS.

PMID- 1403095
TI  - Norepinephrine inhibits calcium currents and EPSPs via a G-protein-coupled
      mechanism in olfactory bulb neurons.
AB  - The most pronounced effect of norepinephrine (NE) in the olfactory bulb is
      disinhibition of mitral/tufted (M/T) cells. Although it has been previously
      proposed that the effects of NE are mediated by a direct inhibitory action on
      granule cells, we have demonstrated that NE could exert it effects through
      inhibition of excitatory synaptic transmission from M/T cells to granule cells
      (Trombley and Shepherd, 1992). In order to define further the mechanism
      underlying NE-mediated inhibition of synaptic transmission, the effects of NE on
      calcium channel currents were examined using whole-cell recording techniques on
      bulb neurons in primary culture. NE inhibited high-threshold calcium currents at
      concentrations that were effective in reducing synaptic transmission. Clonidine,
      but not isoproterenol, mimicked the effects of NE on calcium currents, suggesting
      that the effects were mediated through activation of presynaptic alpha-adrenergic
      receptors. The effects of NE on calcium currents were irreversible in the
      presence of internal GTP-gamma S and prevented by preincubation with pertussis
      toxin, results that are consistent with a G-protein-coupled mechanism.
      Preincubation with pertussis toxin also prevented the effects of NE on synaptic
      transmission, suggesting that a similar G-protein couple mechanism mediates both
      effects. Intracellular dialysis with staurosporin or calcium buffering with EGTA
      did not prevent the effects of NE, suggesting that neither protein
      phosphorylation nor elevated intracellular calcium were required. These results
      suggest that NE may inhibit synaptic transmission in the olfactory bulb by
      reducing calcium currents via a G-protein-coupled alpha-adrenergic receptor.

PMID- 1403096
TI  - Denervation of the motor endplate results in the rapid expression by terminal
      Schwann cells of the growth-associated protein GAP-43.
AB  - Developing and regenerating neurons express high levels of the growth-associated
      phosphoprotein GAP-43. This membrane protein is not confined to neurons, however,
      as a number of studies have demonstrated GAP-43 immunoreactivity in central and
      peripheral glia in vitro and in vivo. We have found that the Schwann cells
      overlying the terminal motor axon at adult rat skeletal muscle endplates, and the
      motor axons themselves, are normally not GAP-43 immunoreactive. Within 24 hr of
      denervation, however, the terminal Schwann cells are positive for a GAP-43 mRNA
      in situ hybridization signal and are GAP-43 immunoreactive. The immunoreactive
      GAP-43 cells possess elaborate processes that branch from the endplate region
      into the perisynaptic zone and stain with defined Schwann cell markers: the
      calcium binding protein S100 and the low-affinity NGF receptor (NGFr), but not
      with a fibroblast marker, Thy-1. Reinnervating motor axons are GAP-43 positive,
      with an appearance quite different from the GAP-43-positive Schwann cells. The
      reappearance of nerve endings at the motor endplate is followed by the
      disappearance of GAP-43 labeling in the Schwann cells and of a retraction of
      their processes. GAP-43 expression in Schwann cells is therefore state dependent,
      apparently regulated by neural contact. This protein, which is associated in
      neurons with neurite formation, may participate in the elaboration of processes
      by Schwann cells when their contact with axons is disrupted.

PMID- 1403098
TI  - A confocal laser microscopic study of enkephalin-immunoreactive appositions onto
      physiologically identified neurons in the rostral ventromedial medulla.
AB  - Neurons in the rostral ventromedial medulla (RVM) are important in the opioid
      modulation of dorsal horn nociceptive transmission. Systemically administered
      morphine inhibits one class of RVM cells, the on-cells; excites a second class of
      RVM cells, the off-cells; and has no effect on a third class, neutral cells. In
      contrast, iontophoretic application of morphine inhibits on-cells but does not
      alter the activity of either off- or neutral cells. The present study addresses
      whether the differential sensitivity to exogenous opioids is correlated with a
      differential termination pattern onto the three classes of RVM neurons by
      afferents containing endogenous opioids. Intracellular recordings were made from
      RVM neurons in rats under light halothane anesthesia. Physiologically
      characterized neurons were injected with Neurobiotin and then subsequently
      visualized with a Texas red fluorophore. Thick (50 microns) sections containing
      labeled RVM cells were processed for enkephalin immunoreactivity (ENK-IR) using
      an FITC fluorophore and then optically sectioned at 1.5 micron intervals using a
      dual-channel confocal laser scanning microscope. ENK-IR appositions were found on
      the somata and dendrites of all on-cells. Although ENK-IR varicosities were also
      apparently apposed to off- and neutral cells, the density of such appositions was
      significantly less than the density of ENK-IR appositions onto on-cells. The
      greater overall density of ENK-IR appositions onto on-cells was apparently due to
      a concentration of appositions on the soma and proximal dendrites of these
      neurons. These results support a model of RVM function in which endogenous opioid
      peptides produce an antinociceptive action by a direct inhibitory action on on
      cells that facilitate nociceptive transmission. This on-cell inhibition may
      produce an additional antinociceptive effect by removing a possible on-cell
      inhibition of off-cells, which are thought to inhibit nociceptive transmission.

PMID- 1403097
TI  - Colocalization of NGF binding sites, trk mRNA, and low-affinity NGF receptor mRNA
      in primary sensory neurons: responses to injury and infusion of NGF.
AB  - The distributions of mRNAs for the protooncogene trk and the low-affinity NGF
      receptor (LNGFR) were studied by hybridization with oligonucleotide probes on
      sections of adult rat primary sensory and sympathetic ganglia. For comparison
      with high-affinity binding sites, adjacent sections were processed for NGF
      receptor radioautography. Among neurons in lumbar dorsal root ganglia and
      trigeminal ganglia, trk mRNA and NGF-binding sites were closely colocalized; this
      finding together with previous direct evidence in other cell types is taken to
      indicate that trk protein is an essential component of the high-affinity NGF
      receptor in adult sensory neurons. In lumbar dorsal root ganglia and trigeminal
      ganglia, abundant LNGFR mRNA was found in all neurons with strong 125I-NGF
      labeling and on additional neurons lacking high-affinity NGF-binding sites. The
      presence of abundant LNGFR in neurons with high-affinity receptors could be the
      cause and/or consequence of their ability to respond to NGF. Neurons with
      abundant LNGFR mRNA but few high-affinity NGF-binding sites may have receptors
      for other members of the neurotrophin family. In nodose ganglia, neurons with
      high concentrations of LNGFR mRNA greatly outnumbered the small percentage with
      abundant trk mRNA. Following intrathecal infusion of NGF to otherwise normal
      dorsal root ganglia, the concentrations of LNGFR mRNA but not those of trk mRNA
      and NGF-binding sites were increased in NGF-responsive neurons. The usual single
      normal pattern of frequency histograms of LNGFR labeling indices became bimodal
      in response to NGF. Concentrations of NGF-binding sites, LNGFR mRNA, and trk mRNA
      were all decreased by peripheral nerve transection and restored by exogenous NGF,
      the restoration being complete for LNGFR mRNA and partial for trk mRNA and NGF
      binding sites. The data indicate that NGF can regulate both LNGFR and trk mRNAs
      but do not clarify the possible contribution of the LNGFR protein to high
      affinity binding sites.

PMID- 1403099
TI  - The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely
      distributed at synapses in rat brain.
AB  - The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist
      occupied beta-adrenergic receptor to promote rapid receptor uncoupling from Gs,
      thereby attenuating adenylyl cyclase activity. Beta ARK-mediated receptor
      desensitization may reflect a general molecular mechanism operative on many G
      protein-coupled receptor systems and, particularly, synaptic neurotransmitter
      receptors. Two distinct cDNAs encoding beta ARK isozymes were isolated from rat
      brain and sequenced. The regional and cellular distributions of these two gene
      products, termed beta ARK1 and beta ARK2, were determined in brain by in situ
      hybridization and by immunohistochemistry at the light and electron microscopic
      levels. The beta ARK isozymes were found to be expressed primarily in neurons
      distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2
      immunoreactivities were present both in association with postsynaptic densities
      and, presynaptically, with axon terminals. The beta ARK isozymes have a regional
      and subcellular distribution consistent with a general role in the
      desensitization of synaptic receptors.

PMID- 1403100
TI  - Cortical area V4 and its role in the perception of color.
AB  - The color and lightness vision of three monkeys with bilateral removal of
      cortical area V4 and three unoperated controls were tested by measuring their
      ability to discriminate between two rows of colored or gray stimuli. In one row,
      the stimuli were ordered in terms of either chromaticity or luminance, whereas in
      the other row they were disordered. Their ability to select the odd-one-out in an
      array of colors or grays and to select the colored patch from an array of
      achromatic grays was also assessed. Unlike an achromatopsic patient tested
      previously in an identical fashion, monkeys with V4 lesions performed
      indistinguishably from controls in the oddity test. The animals lacking V4 were
      slightly impaired at discriminating between ordered and disordered arrays of
      colors or grays, but the color impairment was no more severe than the impairment
      with grays. These deficits were readily accounted for in terms of the conspicuous
      deficits in pattern discrimination apparent in a nine-choice pattern oddity task.
      The results do not support the view that cortical area V4 in the monkey is the
      homolog of the cortical "color center" in humans, located in the lingual and
      fusiform gyri and damage to which leads to the clinical syndrome of cerebral
      achromatopsia, unless it is the additional damage to underlying white matter that
      leads to the severe color disorder in patients.

PMID- 1403101
TI  - Electrophysiological and morphological properties of rat basolateral amygdaloid
      neurons in vitro.
AB  - Electrophysiological and morphological properties of neurons in the rat
      basolateral amygdala (BLA) were assessed using intracellular recordings in brain
      slice preparations. The vast majority of cells studied were identified as
      pyramidal cells on the basis of their accommodation response and by a prominent
      afterhyperpolarization that followed a current-evoked burst of action potentials.
      The second class of cells consisted of late-firing neurons that were
      distinguished electrophysiologically by their very negative resting membrane
      potential (-82 mV) and conspicuous delay in the onset of spike firing in response
      to depolarizing current injection. The third class of cells, termed fast-firing
      neurons, possessed many of the features of intrinsic inhibitory interneurons
      found elsewhere in the brain. These included very brief action potentials (0.7
      msec), a relatively depolarized resting membrane potential (-62 mV), and
      spontaneous firing at a high rate and the absence of spike frequency
      accommodation. Intracellular labeling with Lucifer yellow of
      electrophysiologically identified pyramidal and late-firing cells showed them to
      have pyramidal to stellate cells bodies and spine-covered dendrites. Although
      having an overall pyramidal-like morphology, late-firing neurons possessed cells
      bodies and dendritic fields that were smaller than those of pyramidal cells.
      Lucifer yellow-labeled fast-firing neurons had a nonpyramidal morphology, with
      somata that were spherical to multipolar in shape and spine-sparse or aspiny
      dendrites. The morphological features of these cells corresponded closely to
      those of GABA-containing interneurons that have been described previously in the
      rat BLA using immunohistochemical techniques (McDonald, 1985b). Thus, it seems
      likely that activation of fast-firing neurons underlies inhibitory synaptic
      events that are recorded in the rat BLA. Our data support the conclusion derived
      from previous anatomical studies that pyramidal neurons constitute the
      predominant cell type in the BLA and function as projection neurons in this
      region of the amygdala. The determination of whether late-firing cells constitute
      a unique class of projection neurons distinct from pyramidal cells must await the
      outcome of studies in which the anatomical terminations of this cell type are
      specified.

PMID- 1403102
TI  - Evidence for conditional neuronal activation following exposure to a cocaine
      paired environment: role of forebrain limbic structures.
AB  - The reinforcing properties of cocaine can readily become associated with salient
      environmental stimuli that acquire secondary reinforcing properties. This form of
      classical conditioning is of considerable clinical relevance as intense craving
      can be evoked by the presentation of stimuli previously associated with the
      effects of cocaine. To understand better the neurobiology of cocaine-induced
      environment-specific conditioning, Fos expression was examined in the forebrain
      of rats exposed to an environment in which they had previously received cocaine.
      These results were compared to those observed following an acute injection of
      cocaine. Consistent with its stimulant actions, cocaine produced an increase in
      locomotion that was accompanied by an increase in Fos expression within specific
      limbic regions (cingulate cortex, claustrum, piriform cortex, lateral septal
      nucleus, paraventricular nucleus of the thalamus, lateral habenula, and amygdala)
      as well as the basal ganglia (dorsomedial striatum and nucleus accumbens).
      Exposure of rats to the cocaine-paired environment also produced an increase in
      locomotion, as compared to various control groups. In addition to this behavioral
      effect, conditioned subjects exhibited a significant increase in Fos expression
      within the cingulate cortex, claustrum, lateral septal nucleus, paraventricular
      nucleus of the thalamus, lateral habenula, and the amygdala, suggesting increased
      neuronal activity within these regions. In contrast to the dramatic effects
      observed within these structures, no conditional activation was observed within
      the piriform cortex, nucleus accumbens, or dorsal striatum, suggesting that these
      brain areas are not involved in the conditioned response. The present findings
      indicate that specific limbic regions exhibit increased neuronal activation
      during the presentation of cocaine-paired cues and may be involved in the
      formation of associations between cocaine's stimulant actions and the environment
      in which the drug administration occurred. Although the nucleus accumbens is
      necessary for the reinforcing and locomotor effects of cocaine, it does not
      exhibit a conditional Fos response, suggesting that different neural circuits are
      involved in the unconditioned and conditioned effects of cocaine.

PMID- 1403103
TI  - Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal
      pyramidal cells.
AB  - Using intracellular recording techniques in CA1 cells in the hippocampal slice,
      we studied the responses of cells to synaptically released and iontophoretically
      applied GABA. With high-resistance, Cl(-)-filled electrodes, which inverted and
      enlarged the responses at normal resting potentials, we examined spontaneous GABA
      mediated IPSPs. Usually we recorded the spontaneous events in the presence of
      carbachol (10-25 microM), which significantly increased IPSP frequency and
      blocked potentially confounding K+ conductances. Following a train of action
      potentials, spontaneous IPSPs were transiently suppressed. This suppression could
      not be accounted for by membrane conductance changes following the train or
      activation of a recurrent circuit. Whole-cell voltage-clamp recordings in the
      slice indicated that the amplitudes of the spontaneous GABAA inhibitory
      postsynaptic currents (IPSCs) were also diminished following the action potential
      train. In some cases BAY K 8644, a Ca2+ channel agonist, enhanced the suppression
      of IPSPs, while buffering changes in [Ca2+]i with EGTA or BAPTA prevented it. The
      monosynaptically evoked IPSC in the presence of 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX) and dl-2-amino-5-phosphonovaleric acid (APN) was also diminished
      following a train of action potentials; however, iontophoretically applied GABA
      responses did not change significantly. These studies suggest that localized
      physiological changes in postsynaptic [Ca2+]i potently modulate synaptic GABAA
      inputs and that this modulation may be an important regulatory mechanism in
      mammalian brain.

PMID- 1403104
TI  - The AANS: the national and international organization for neurological surgery.
AB  - The President of the American Association of Neurological Surgeons (AANS)
      validates the AANS as the national neurosurgical organization. He describes
      improved management of major committees of neurological surgery by the Joint
      Officers of the AANS and the Congress of Neurological Surgeons. A strong argument
      and proclamation are presented to expand the international role of the former
      Harvey Cushing Society.

PMID- 1403105
TI  - Long-term evaluation of decompressive surgery for degenerative lumbar stenosis.
AB  - One-hundred patients who had undergone decompressive surgery for lumbar stenosis
      between 1980 and 1985 were evaluated as to their long-term outcome. Four patients
      with postfusion stenosis were included. A 5-year follow-up period was achieved in
      88 patients. The mean age was 67 years, and 80% were over 60 years of age. There
      was a high incidence of coexisting medical diseases, but the principal disability
      was lumbar stenosis with neurological involvement. Results were categorized as
      either a surgical success or a failure, depending upon the achievement of preset
      goals within the context of lifestyle and needs. There were no perioperative
      complications. Initially there was a high incidence of success, but recurrence of
      neurological involvement and persistence of low-back pain led to an increasing
      number of failures. By 5 years this number had reached 27% of the available
      population pool, suggesting that the failure rate could reach 50% within the
      projected life expectancies of most patients. Of the 26 failures, 16 were
      secondary to renewed neurological involvement, which occurred at new levels of
      stenosis in eight and recurrence of stenosis at operative levels in eight.
      Reoperation was successful in 12 of these 16 patients, but two required a third
      operation. The incidence of spondylolisthesis at 5 years was higher in the
      surgical failures (12 of 26 patients) than in the surgical successes (16 of 64).
      Spondylolisthetic stenosis tended to recur within a few years following
      decompression. To forestall recurrences, it is suggested that stabilization be
      carried out at levels of spondylolisthetic stenosis and the initial decompression
      include adjacent levels of threatening symptomatic stenosis. However, the
      heterogenicity of this patient population, with varying patterns and levels of
      symptomatic stenosis, precludes application of rigid surgical protocols.

PMID- 1403106
TI  - The significance for postoperative hearing of preserving the labyrinth in
      acoustic neurinoma surgery.
AB  - Among 186 patients with preoperative hearing, a total of 189 acoustic neurinomas
      were removed through a lateral suboccipital approach with anatomical preservation
      of the cochlear nerve. Functional hearing was preserved in 92 (49%) of these
      patients; despite anatomical preservation of the cochlear nerve, deafness was the
      result in 51% of the series. Many factors have been considered to cause hearing
      loss in patients whose cochlear nerve was intact after surgery; these include
      nerve retraction, nerve or cochlear ischemia, overheating and vibration damage to
      the nerve, and opening of the labyrinth. To evaluate the significance of injury
      to the labyrinth in postoperative hearing loss, a prospective study was
      undertaken. High-resolution computerized tomography studies through the inner ear
      with bone algorithm were performed pre- and postoperatively. The postoperative
      status of the labyrinth was classified into three patterns: intact, fenestrated,
      and widely opened. Injury to the labyrinth occurred in 30% of the cases. The most
      frequently injured labyrinth structures were the crus commune of the posterior
      and superior semicircular canals (52%), the posterior semicircular canal (23%),
      the vestibule (21%), and the superior semicircular canal (4%). A statistically
      significant relationship was found between injury to the labyrinth and deafness,
      elevated thresholds, and lower discrimination values at pure-tone audiograms and
      speech audiometry (p < 0.0001). The degree of the injury (comparison between
      fenestration and wide opening of the labyrinth) was also significantly related to
      postoperative deafness (p < 0.0001). Disturbance of the inner-ear fluids was
      considered to be the cause of the hearing loss. In 12 patients labyrinth injury
      was not associated with deafness. This finding may support the existence of
      mechanisms of cochlear protection. The homeostatic function of the endolymphatic
      sac was considered to play an important role in recovery of damaged hearing in
      these 12 cases.

PMID- 1403107
TI  - Late course of preserved hearing and tinnitus after acoustic neurilemoma surgery.
AB  - The late course of preserved hearing and tinnitus following retrosigmoid
      transmeatal surgery for acoustic neurilemoma is reported. Over a period of 5
      years, useful hearing was preserved in 15 patients after preservation was
      attempted in 42 patients. In five patients the hearing was better than the
      preoperative level; in three it was worse. Three patients developed delayed
      worsening and fluctuations of hearing in the surgically treated ear during a
      median follow-up period of 2 1/2 years. While the exact reason for such worsening
      was not clear in two patients, in one patient it appeared that the muscle graft
      placed in the internal auditory canal after tumor resection resulted in fibrosis
      and compromise of the cochlear nerve. The causes of delayed worsening of hearing
      in the absence of tumor recurrence are analyzed, and possible treatment and
      methods of prevention of worsening are suggested. In six patients, tinnitus
      persisted after surgery in the ear with successful preservation of hearing, but
      hearing was not worsened and the tinnitus was not bothersome to the patient. In
      one patient with preoperative tinnitus, hearing was not preserved and tinnitus
      persisted sufficiently to necessitate reexploration and cochlear nerve section.

PMID- 1403108
TI  - The benign course of cavernous carotid artery aneurysms.
AB  - Recently, the benign nature of aneurysms of the cavernous carotid artery has been
      questioned. In a review of cases evaluated from 1980 to 1990 with this
      developmental aneurysm, the authors found 70 patients with 79 cavernous carotid
      artery aneurysms. As expected, the great majority (59 patients) had
      ophthalmoplegia as the initial problem. Retro-orbital pain (three cases) and a
      carotid-cavernous fistula (five cases) were infrequently the sole manifestation.
      Mirror-image asymptomatic aneurysms were found in nine patients and asymptomatic
      cavernous aneurysms were found in three additional patients. Thirty-four patients
      not surgically treated were followed for a mean of 2.8 years, and 36 surgical
      patients were followed for a mean of 4.1 years prior to treatment. Of the 79
      aneurysms, one (1.3%) ruptured into the subarachnoid space during this period.
      Other than optic neuropathy or cranial neuropathy, no patient had a permanent
      neurological deficit; the 12 asymptomatic aneurysms remained asymptomatic. It is
      concluded that an aneurysm of the cavernous carotid artery is rarely associated
      with life-threatening complications, and treatment should be considered
      principally for patients with intolerable pain or problems related to vision.

PMID- 1403109
TI  - Cell-mediated immunity in severely head-injured patients: the role of suppressor
      lymphocytes and serum factors.
AB  - Severe head injury results in suppression of cellular immunity associated with
      defective in vitro functioning of effector lymphocytes, such as helper T cells
      and cytotoxic T cells. It is not known whether this suppression in effector
      lymphocyte function is due to intrinsic lymphocyte dysfunction, to suppressor
      peripheral blood mononuclear cells (PBMC's) such as suppressor lymphocytes or
      suppressor monocytes, or to serum factors capable of inhibiting effector
      lymphocyte function. The purpose of this study was to determine whether a
      subpopulation of PBMC's and/or serum factor(s) are responsible for this observed
      suppression in cell-mediated immunity. Cell-mediated immune activity was
      determined measuring in vitro lymphokine-activated killer (LAK) cytotoxicity
      following incubation of PBMC's from 15 head-injured patients with those from 15
      heterologous normal subjects. The PBMC's were separated into lymphocyte-enriched
      and monocyte-enriched subpopulations by plastic adherence techniques, and the
      effect of each population on LAK cytotoxicity was determined. Additionally, the
      effect on cytotoxicity of serum from the head-injured patients was determined in
      a dose-response fashion. There was significant depression in LAK cytotoxicity
      when: 1) PBMC's from normal subjects were incubated with PBMC's from head-injured
      patients (p < 0.001); 2) lymphocytes (PBMC's depleted of monocytes) from head
      injured patients were incubated with PBMC's from normal subjects (p < 0.001); and
      3) PBMC's from normal subjects were incubated with serum from head-injured
      patients (p < 0.001). No suppression in cellular immunity was noted when
      lymphocytes from normal subjects were incubated with monocytes from head-injured
      patients. The results indicate that lymphocytes rather than monocytes actively
      inhibit cellular immunity following severe head injury. The detection of
      immunosuppressive serum factors suggests a mechanism by which lymphocytes might
      be modulated by severe head injury.

PMID- 1403110
TI  - Pediatric spinal injury: review of 174 hospital admissions.
AB  - Injury to the spinal column and spinal cord occurs relatively infrequently in the
      pediatric population. A review of 174 pediatric patients is presented,
      representing 5.4% of all patients admitted with spinal injury. Spinal cord injury
      was present in 45% of patients. A distinct injury profile, explained by
      anatomical and biomechanical features, distinguishes the young patient with an
      immature spine from older adolescents with a more mature, adult-like spine. The
      younger patients, while less likely to have spinal injury, had a higher incidence
      of neurological injury, in addition to a higher frequency of both spinal cord
      injury without radiological abnormality and upper cervical cord injury. In
      addition, younger patients with spinal cord injury and no radiological
      abnormality were more likely to have complete or severe cord injury. Prognosis
      was determined by the severity of spinal cord injury. Patients with complete cord
      injuries showed little improvement, while patients with incomplete injuries
      generally fared much better, with 74% showing significant improvement and 59%
      experiencing a complete recovery of neurological functions. There were six
      deaths, but none was attributed solely to spinal injury. The authors conclude
      that outcome is quite good after pediatric spinal cord injury that does not
      produce a physiologically complete cord deficit.

PMID- 1403111
TI  - Pediatric spinal injury: review of 61 deaths.
AB  - Injury to the spinal column and spinal cord occurs relatively infrequently in the
      pediatric population. The authors present a unique review of 61 pediatric deaths
      associated with spinal injury. This group represented 28% of the total pediatric
      spine-injured population and 45% of the total pediatric spinal cord-injured group
      studied. The ratio of pediatric to adult spinal injury mortality was 2.5:1. Of
      the 61 children, 54 (89%) died at the accident scene. Thirty patients underwent a
      complete autopsy, 19 of whom had an Abbreviated Injury Scale Grade 6 injury
      (maximum score, untreatable). Spinal cord injury was found to be the cause of
      death in only eight children and was associated with injury to the high cervical
      cord and cardiorespiratory arrest. These children typically sustained severe
      multiple trauma. In this population, there appears to be little room for improved
      outcome through changes in treatment strategy.

PMID- 1403112
TI  - The subtemporal, transcavernous, anterior transpetrosal approach to the upper
      brain stem and clivus.
AB  - The temporal lobe, posterolateral cavernous sinus, tentorium, and petrous apex
      restrict anterolateral surgical access to lesions of the upper brain stem and
      clivus. The authors describe a modified transpetrosal approach that enhances the
      exposure of clival chordomas and aneurysms of the basilar artery bifurcation. An
      intradural and extradural subtemporal approach is combined with division of the
      tentorium and superior petrosal sinus, posterolateral dissection of the cavernous
      sinus, and intradural removal of the petrous bone from its apex to the cochlea.
      The indications, advantages, and disadvantages of this subtemporal,
      transcavernous, anterior transpetrosal approach are described in detail, along
      with its use in six patients.

PMID- 1403113
TI  - Endovascular treatment of intracranial dural arteriovenous fistulas with spinal
      perimedullary venous drainage.
AB  - Intracranial dural arteriovenous (AV) fistulas with spinal perimedullary venous
      drainage are rare lesions that have distinctive clinical, radiological, and
      therapeutic aspects. Five patients presented with an ascending myelopathy, which
      extended to involve the brain stem in three cases. Myelography and magnetic
      resonance imaging showed slightly dilated spinal perimedullary vessels. Spinal
      angiograms were normal in the arterial phase. Diagnosis was only possible after
      cerebral angiography, which demonstrated posterior fossa AV fistulas fed by
      meningeal arteries and draining into spinal perimedullary veins. Endovascular
      treatment alone resulted in angiographic obliteration of the lesion in three
      patients. Two patients required surgery in addition to endovascular therapy. One
      patient died postoperatively, and in one a transient complication of embolization
      was observed. Improvement after treatment was good in two cases and fair in two.
      Transverse sinus thrombosis was observed in three cases and was probably the
      cause of the aberrant venous drainage of the fistula into the spinal
      perimedullary veins. The pathophysiology is related to spinal cord venous
      hypertension. These lesions were classified as Type 5 in the Djindjian and
      Merland classification of dural intracranial AV fistulas. Endovascular therapy is
      a safe effective method in the treatment of these fistulas and should be tried
      first.

PMID- 1403114
TI  - Hypoglossal-facial nerve anastomosis for facial nerve palsy following surgery for
      cerebellopontine angle tumors.
AB  - Hypoglossal-facial nerve anastomosis is one of the procedures frequently
      performed to restore function after facial palsy secondary to surgery for removal
      of cerebellopontine angle tumors. The published results of hypoglossal-facial
      nerve anastomosis have been variable, and there are still questions about the
      indications, timing, and surgical techniques for this procedure. The goals of the
      present retrospective analysis of 22 cases of hypoglossal-facial nerve
      anastomosis were to assess the extent of the functional recovery and to analyze
      the factors affecting this recovery. The 22 cases of complete facial palsy were
      gleaned from a series of 245 cases of cerebellopontine angle tumors treated
      surgically by one of the authors. Twenty patients had an acoustic neuroma
      (average size 3.5 cm), one patient had a petrous meningioma, and one patient had
      a facial neuroma. The average age of the patients was 47.3 years (range 19 to 69
      years). The average interval from tumor surgery to hypoglossal-facial nerve
      anastomosis was 6.4 months (range 12 days to 17 months), and the average follow
      up period after the procedure was 65 months. The results were graded as good,
      fair, poor, or failure according to a new method of classifying facial nerve
      function after hypoglossal-facial nerve anastomosis. The results were good in 14
      cases (63.6%), fair in three (13.6%), and poor in four (18.2%); one (4.5%) was a
      failure. Good and fair results occurred with higher frequency in younger patients
      who were operated on within shorter intervals, although these relationships were
      not statistically significant. There were no surgical complications. Good or fair
      results were achieved in 17 (77.3%) of the 22 cases, and thus hypoglossal-facial
      nerve anastomosis is considered an effective procedure for most patients with
      facial palsy after surgery for cerebellopontine angle tumors.

PMID- 1403115
TI  - 99mTc-hexamethylpropyleneamine oxime leukocyte scintigraphy and C-reactive
      protein levels in the differential diagnosis of brain abscesses.
AB  - The demonstration and accurate localization of intracerebral mass lesions are
      commonly performed with computerized tomography (CT), which often cannot
      determine the nature of the lesion. As an aid in the differential diagnosis
      between brain abscess and neoplasm, the authors have evaluated both 99mTc
      hexamethylpropyleneamine oxime (99mTc-HMPAO) leukocyte scintigraphy and the serum
      C-reactive protein level. Of 23 patients with intracranial mass lesions, 22
      individuals showed ring-like contrast enhancement on CT scans; the one exception
      was a patient treated for a meningioma who had a negative CT scan despite
      clinical suspicion of intra- or extracranial abscess. The final diagnosis was
      invariably established by microscopic examination of tissue specimens. In 10
      patients the final diagnosis was brain abscess; the other 13 patients harbored a
      brain neoplasm (glioma in nine, astrocytoma in one, and metastasis in three). The
      99mTc-HMPAO leukocyte scintigraphy detected all cases of abscess. There were no
      false-positive results. An elevated C-reactive protein level (> 13 mg/liter) was
      found in all but one patient with abscess and in three patients with neoplasm;
      two of these three patients had dental root infections which could account for
      the elevation of C-reactive protein. It is concluded that 99mTc-HMPAO leukocyte
      scintigraphy should be performed when there is a possibility that a brain abscess
      may exist. Any steroid treatment should be discontinued for 48 hours prior to
      leukocyte scintigraphy. Also, C-reactive protein determination should be
      performed and is useful even when steroids are given.

PMID- 1403116
TI  - Usefulness of beta 2-transferrin assay in the detection of cerebrospinal fluid
      leaks following head injury.
AB  - The clinical value of analyzing various fluids and exudates for beta 2
      transferrin (beta 2-Tfn) to detect cerebrospinal fluid (CSF) leakage following
      head trauma was reviewed in a series of 11 cases. Qualitative detection of beta 2
      Tfn was performed by agarose gel electrophoresis of tears, ear and nose exudates,
      cerebral cyst fluid, and wound discharge fluid in different cases. In each
      instance the presence of beta 2-Tfn in the analyzed fluid supported the diagnosis
      of a CSF leak. Equally, the demonstration of the absence of beta 2-Tfn in the
      fluid excluded the diagnosis of such a leak. Neither false-positive nor false
      negative results were found, as indicated by separate radiological investigations
      and/or subsequent clinical assessment of patients. The detection of beta 2-Tfn in
      suspect fluids thus provides a highly sensitive and selective, rapid, and
      noninvasive test for the detection of CSF leakage in cases of head trauma.

PMID- 1403117
TI  - Is vasospasm related to proliferative arteriopathy?
AB  - Although proliferative arteriopathy has been postulated to play a role in the
      etiology of vasospasm after subarachnoid hemorrhage (SAH), histological and
      morphological studies examining cerebral vasospasm have produced conflicting
      results. To help settle this controversy, the authors used an in vivo label of
      cell division, bromodeoxycytidine, to assess cell proliferation in a primate
      model of SAH. Fifteen cynomolgus monkeys received a clot of either whole blood
      (11 animals) or red blood cells (four animals) placed around the right middle
      cerebral artery (MCA). On the day of surgery continuous intravenous infusion of
      bromodeoxycytidine was begun and continued until the animal was sacrificed
      immediately after arteriography on Day 7, 12, or 27 following surgery. Sections
      from the right and left MCA's were stained with a monoclonal antibody against
      bromodeoxcytidine, and labeled cells were counted. Arteriographic evidence of
      vasospasm occurred in nine monkeys on Day 7. On Day 12 and Day 27 no monkeys had
      persistent vasospasm. Placement of subarachnoid clot around the right MCA
      increased proliferative activity across all layers of the arterial wall. Most of
      the labeled cells were in the adventitia and the endothelium. Although there were
      more dividing cells in all layers of the right MCA than the left MCA (p < 0.01),
      the number of stained cells per section was limited (range 0.1 to 21.2, mean 8)
      and the occurrence of vasospasm was not associated with the number of dividing
      cells in the right MCA on Day 7, 12, 27, or for all days combined (p > 0.6).
      Cerebral vasospasm after SAH was not associated with the extent of proliferation
      of cells in the vessel wall, nor could the intensity of the limited proliferative
      changes have been responsible for narrowing of the vessel diameter.

PMID- 1403118
TI  - Expression of cell adhesion molecule E-cadherin in human arachnoid villi.
AB  - Calcium-dependent epithelial cell adhesion molecules designated as E-cadherin
      (also known as uvomorulin or L-CAM) were identified in human arachnoid villi by
      immunoblotting and immunocytochemical analyses using a monoclonal antibody HECD-1
      raised against human mammary carcinoma MCF-7 cells. Immunoblot analysis showed
      that HECD-1 recognizes E-cadherin with a molecular weight of 124 kD. In all
      arachnoid cells of an arachnoid villus, E-cadherin was detected by immunolight
      microscopy within the cytoplasm rather than the cellular boundaries as seen in
      the control group. Furthermore, the extent of expression by immunolight
      microscopy varied from portion to portion. The expression was usually weak in the
      syncytial cluster which was ultrastructurally composed of tightly juxtaposed
      cells characterized by few extracellular cisterns and numerous cell junctions,
      while it was intense in the reticular cluster and the surface layer which were
      ultrastructurally characterized by abundant extracellular cisterns and smaller
      numbers of cell junctions. The cells of the reticular cluster and the surface
      layer contained more free ribosomes than those of the syncytial cluster.
      Immunoelectron microscopy showed that E-cadherin was localized not only to the
      opposing plasma membranes and the cytoplasm around the free ribosomes or the
      rough endoplasmic reticulum but also to the extracellular cisterns. As the
      expression of E-cadherin was closely related to the arachnoid cells adjacent to
      the cerebrospinal fluid pathway, it is suggested that, instead of the cell
      junctions, E-cadherin may play an important role in the flexible adhesion of
      arachnoid cells even in the presence of the cerebrospinal fluid.

PMID- 1403119
TI  - Antitumor activity against established intracerebral gliomas exhibited by
      cytotoxic T lymphocytes, but not by lymphokine-activated killer cells.
AB  - Specific immune responses against malignant brain tumors have been difficult to
      demonstrate. Moreover, immunotherapy has met with little success, despite using
      lymphocytes with high levels of cytotoxicity against brain tumor cells.
      Lymphokine-activated killer (LAK) cells that nonspecifically kill brain tumor
      cells are produced by stimulating resting precursors with high concentrations of
      interleukin-2 (IL-2). Cytotoxic T lymphocytes that specifically kill brain tumor
      cells are produced by stimulating antigen receptor-positive immune-cell
      precursors with tumor cells. In an attempt to gain insight into immune cell
      function against brain tumors, the present study compared the in vitro and in
      vivo activities of LAK cells and cytotoxic T lymphocytes produced against RT2, a
      fast-growing rat glioma cell line. Lymphokine-activated killer cells were
      produced by stimulating normal rat spleen cells with 1000 units of IL-2, and RT2
      specific cytotoxic T lymphocytes were produced by priming them in vivo with RT2
      and Corynebacterium parvum and restimulating primed spleen cells with RT2 in
      vitro. Lymphokine-activated killer cells were highly cytotoxic for a panel of
      syngeneic and allogeneic brain tumor and non-brain tumor target cells, including
      RT2, as measured in a 4-hour 51Cr release assay. Cytotoxic T lymphocytes were
      highly cytotoxic only for syngeneic brain tumor target cells. Lymphokine
      activated killer cells and cytotoxic T lymphocytes were tested for in vivo
      antitumor activity against intracerebral RT2 by intravenous adoptive transfer of
      activated lymphocytes. Untreated rats died in approximately 2 weeks. Lymphokine
      activated killer cells plus IL-2 failed to affect survival when treatment was
      initiated as early as 1 day following tumor inoculation. Cytotoxic T lymphocytes
      and IL-2 administered as late as Day 5 rejected progressing intracerebral tumor.
      Thus, although both cytotoxic T lymphocytes and LAK cells exhibited high levels
      of in vitro killing of glioma cells, only cytotoxic T lymphocytes rejected
      progressing intracerebral tumors.

PMID- 1403120
TI  - Inhibition of delayed arterial narrowing by the iron-chelating agent
      deferoxamine.
AB  - The potential role of iron in cerebral vasospasm was examined in the rat femoral
      artery model by the perivascular application of deferoxamine, a ferric ion
      chelator and antioxidant. In 25 rats, platelet-rich plasma or fresh autologous
      whole blood containing deferoxamine at concentrations of 1, 5, 10, or 15 mg/ml
      was applied to the adventitial surface of the femoral artery in a Silastic cuff
      to insure chronic exposure to the vessel wall. At 7 days, contralateral femoral
      arteries exposed to whole blood showed a 70% reduction in luminal cross-sectional
      area and morphological changes associated with vasospasm. Application of platelet
      rich plasma or whole blood containing deferoxamine at 25 mg/ml produced no
      significant arterial narrowing or structural changes; significant intermediate
      reductions in arterial narrowing were observed at deferoxamine concentrations of
      5 and 10 mg/ml. Presaturation deferoxamine (10 mg/ml) with excess ferric ion
      prior to application eliminated the protective effect. In addition, deferoxamine
      chelated the ferric ion released from incubated whole blood in vitro over 7 days
      in a dose-dependent manner consistent with its protective effect in vivo. Ferric
      ion may influence the development of chronic arterial narrowing after
      subarachnoid hemorrhage by a variety of mechanisms.

PMID- 1403121
TI  - Experimental repair of the oculomotor nerve: the anatomical paradigms of
      functional regeneration.
AB  - In adult guinea pigs, the oculomotor nerve was sectioned proximally (at the
      tentorial edge) or more distally (at the orbital fissure) and immediately
      repaired by reapproximation. During a 24-week postoperative period, extrinsic eye
      motility was assessed by analyzing the vestibulo-ocular reflexes. The regenerated
      oculomotor nerve was studied morphometrically on semi-thin histological sections
      at 16 and 24 weeks postinjury. The selectivity of muscle reinnervation was
      investigated by injection of both single (horseradish peroxidase) and double
      (fluorescent dyes) retrograde axonal tracers into the eye muscles. Following
      proximal repair of the oculomotor nerve, the degree of recovery of extraocular
      motility varied among different animals and remained stable over long-term
      observations. In animals with poor recovery, aberrant eye movements were always
      found, and the somatotopic map of the reinnervated eye muscles was greatly
      altered. Distortions of the central representation were also seen in those
      animals in which a good level of functional recovery was seen. However, in
      animals with good recovery, a topographic bias was re-established by about 65% of
      the original neuronal population, as opposed to 26% in the animals with poor
      recovery. Neurons located contralateral to the axotomized nucleus sprouted intra
      axially and projected their axons to denervated eye muscles. The number and
      diameter of the regenerated axons, the number and soma diameter of the axotomized
      neurons, and the ratio of distal axonal branches to proximal supporting neurons
      were all related to the degree of functional recovery. Following repair of the
      oculomotor nerve at the orbital fissure, extraocular motility had recovered in
      all of the animals at 16 weeks without aberrant phenomena. Functional
      regeneration of the distally transected oculomotor nerve is thought to be the
      result of selective muscle reinnervation.

PMID- 1403122
TI  - Intrathecal chemotherapy with ACNU in a meningeal gliomatosis rat model.
AB  - Intrathecal administration of ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2
      chloroethyl)-3-nitroso urea hydrochloride) had a remarkable chemotherapeutic
      effect in a rat model of meningeal gliomatosis. This effect was evaluated in rats
      with meningeal gliomatosis induced by an intracisternal inoculation of rat C6
      glioma cells. The median survival time of the rats treated with a single dose of
      intrathecal ACNU (1 mg/kg) on Day 1 or Day 3 after tumor inoculation was
      significantly prolonged by 35.7% to 42.9% or 25.0% to 28.6%, respectively, as
      compared with that of the control animals. Meningeal gliomatosis rat models
      treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or
      intravenously with ACNU (15 mg/kg) both failed to prolong the survival time of
      the animals. These findings suggest that intrathecal chemotherapy with a low dose
      of ACNU is effective in the early stages of meningeal gliomatosis, whereas
      intravenous chemotherapy with a high dose of ACNU is always ineffective.

PMID- 1403123
TI  - Sustained release of papaverine for the treatment of cerebral vasospasm: in vitro
      evaluation of release kinetics and biological activity.
AB  - Cerebral vasospasm remains an unpredictable and inadequately treated complication
      of aneurysmal subarachnoid hemorrhage. To date, pharmacological treatment has
      been plagued in part by an inability to attain sufficiently high concentrations
      of vasodilator drug in the cerebrospinal fluid without precipitating systemic
      side effects such as hypotension. To circumvent this limitation of current
      pharmacological therapy, the authors have developed a sustained-release
      preparation of papaverine that can be implanted intracranially at the time of
      surgery for aneurysm clipping. In vitro evaluation of drug-release kinetics has
      demonstrated that reliable, sustained release of effective amounts of papaverine
      is possible. An in vitro bioassay using isolated preparations of canine basilar
      artery has confirmed the biological activity of this preparation. These in vitro
      studies are described.

PMID- 1403125
TI  - Posttraumatic cervical spondyloptosis at C6-7 with late-onset cord compression: a
      new clinical entity. Case report.
AB  - An unusual case of total spondyloptosis of the cervical spine at the C6-7 level
      with late-onset cord compression is described in an 8-year-old girl. The patient
      was treated by anterior decompression and in situ fusion as it was thought
      hazardous to try an anatomical reduction. The patient's excellent neurological
      recovery postoperatively strongly supports the use of this treatment protocol.
      The authors believe this is the first report of a posttraumatic spondyloptosis of
      the cervical spine, presenting with a late-onset cord compression. A brief
      summary of the clinical presentation, the surgical technique, and a review of the
      relevant literature is presented.

PMID- 1403124
TI  - Leptomeningeal dissemination of cerebellar pilocytic astrocytoma. Case report.
AB  - A case of surgically treated pilocytic astrocytoma in the cerebellar vermis is
      reported in a patient who subsequently demonstrated multiple subarachnoid nodular
      masses in the cerebrum and spinal cord 6 years after the initial surgery. The
      nodular tumors did not indicate a growth tendency on computerized tomography or
      magnetic resonance imaging over a 2-year observation period. The histology of the
      nodular masses in the cerebrum and spinal cord was similar to that of the
      original tumor. The bromodeoxyuridine labeling index indicated low proliferative
      activity (0.5%). The peculiar pattern of dissemination of the pilocytic
      astrocytoma is described.

PMID- 1403126
TI  - Childhood odontoid fractures evaluated with computerized tomography. Case report.
AB  - A case is presented that illustrates the use of computerized tomography for the
      evaluation of an odontoid fracture in a child. Such a "fracture" may actually
      represent a "synchondrotic slip" of the odontoid and C-2 vertebral body between
      the neural arches of C-2. Treatment should almost always be conservative.
      Complete healing of the injury is expected.

PMID- 1403127
TI  - Remote recurrence of craniopharyngioma in the epidural space. Case report.
AB  - The case is reported of a 28-year-old man with "ectopic" craniopharyngioma
      recurring in the epidural space 21 years after the original tumor was resected.
      Previously described cases of similar remote recurrences as well as some features
      of the biological behavior of craniopharyngioma are discussed. The rarity of this
      postoperative complication is addressed.

PMID- 1403128
TI  - Botulinum toxin enhancement of postoperative immobilization in patients with
      cervical dystonia. Technical note.
AB  - Postoperative immobilization in patients with cervical dystonia requiring fusion
      presents a unique management problem. Two patients with severe degenerative
      cervical spine disease secondary to chronic repetitive motion are reported. Both
      required a surgical fusion and postoperative immobilization. Botulinum toxin was
      injected intramuscularly to assist in immobilization. The technique used is
      described.

PMID- 1403129
TI  - A simple method for distal catheter lengthening of ventriculoperitoneal shunts.
      Technical note.
AB  - A simple technique to lengthen the distal catheter of ventriculoperitoneal shunts
      is described. This method, which utilizes a guidewire, has been successful in
      elective shunt revisions in eight children.

PMID- 1403130
TI  - Saphenous vein graft to the distal vertebral artery between C-1 and C-2 using a
      lateral-anterior approach. Technical note.
AB  - The authors present a modified surgical procedure for extracranial vertebral
      artery reconstruction. The use of the proposed technique results in access to the
      V3 segment of the vertebral artery between the C-1 and C-2 vertebrae through the
      retrojugular space without requiring bone rongeuring. A saphenous vein bypass
      graft was placed between the common carotid artery and the V3 segment of the
      vertebral artery in three patients with bilateral occlusive lesions of the
      proximal vertebral arteries.

PMID- 1403131
TI  - Proliferative potential of T-cell lymphocytes from gliomas.

PMID- 1403132
TI  - Ophthalmological complications in pineal tumor surgery.

PMID- 1403133
TI  - Outcome of radiosurgery for cerebral AVM.

PMID- 1403134
TI  - Lazarus' sign in brain-dead patients.

PMID- 1403135
TI  - Congressional subcommittee scrutinizes looming U.S. radioisotope supply crisis.

PMID- 1403136
TI  - Evaluation of the incremental diagnostic value and impact on patient treatment of
      thallium scintigraphy.
AB  - The incremental diagnostic yield of exercise 201Tl scintigraphy with visual and
      quantitative analysis was determined in 191 patients with known or suspected
      coronary artery disease (CAD). The coronary arteriogram was used as the gold
      standard. After pre-test clinical and exercise electrocardiographic data were
      taken into consideration, scintigraphy was found to have additional diagnostic
      value both in the diagnosis of CAD and of multivessel disease, with quantitative
      analysis being superior to visual analysis. The impact of 201Tl scintigraphy on
      the patient's treatment--conservative treatment versus revascularization--was
      also evaluated. The impact was relatively low, as the decision for
      revascularization was based primarily on the angiographic result and the severity
      of the anginal pain. This result reflects only the decision making process used
      in our clinic and permits no conclusion to be made concerning the possible value
      of 201Tl scintigraphy in this type of medical decision making process.

PMID- 1403137
TI  - Evaluation of the incremental value of a diagnostic test: a worthwhile exercise
      in this era of cost consciousness?

PMID- 1403138
TI  - Iodine-131-metaiodobenzylguanidine and bone scintigraphy for the detection of
      neuroblastoma.
AB  - The purpose of this study was to compare the utility of bone and
      metaiodobenzylguanidine (MIBG) scintigraphy for the detection of primary and
      metastatic deposits of neuroblastoma. 99mTc methylene diphosphonate (MDP) bone
      and 131I-MIBG scans performed within 1 mo of each other in 85 patients with known
      or suspected neuroblastoma were evaluated for evidence of skeletal and
      extraskeletal disease. In 77 of 77 patients with confirmed neuroblastoma, the MDP
      and MIBG scans were concordant for the presence or absence of skeletal disease. A
      nearly twofold greater number of skeletal lesions were evident on MIBG scanning.
      No patients with normal bone scans had MIBG studies indicating bone involvement.
      In patients with histologic evidence of bone marrow involvement, each study
      suggested skeletal lesions in approximately 70%. In patients with extraskeletal
      disease demonstrated by CT, there was soft-tissue uptake of MIBG in 80% and MDP
      in 39%. We conclude that both MIBG and MDP are useful for the detection of
      skeletal neuroblastoma. MIBG is the better agent for characterizing the extent of
      disease, and MDP is a valuable adjunctive agent that provides skeletal landmarks
      for comparison. MIBG is clearly superior for the detection of extraskeletal
      neuroblastoma.

PMID- 1403139
TI  - Quantitative measurement of regional cerebral blood flow using N-isopropyl
      (iodine-123)p-iodoamphetamine and single-photon emission computed tomography.
AB  - We have developed a quantitative method of measuring regional cerebral blood flow
      (rCBF) by using N-isopropyl-(iodine-123)p-iodoamphetamine and single-photon
      emission computed tomography (SPECT). Twenty-five dynamic SPECT images (24
      sec/scan) were collected immediately after tracer injection using a ring-type
      SPECT system and the accumulation curve (C(t)) was obtained. The time-activity
      curve corresponding to the arterial blood activity curve was used as B(t). The
      latter curve was calculated from the lung time-activity curve monitored during
      scanning and corrected by the actual activity obtained by one-point blood
      sampling 5 min after tracer injection. The octanol extraction ratio during
      scanning was considered to be constant and taken as the value measured 5 min
      after tracer injection (E). The uptake constant (K) per pixel was calculated by
      the least squares fitting method as the slope of the linear relationship in which
      C(t)/E x B(t) was plotted against E x integral of t(o)B(tau)d tau/E x B(t).
      Functional maps of rCBF values were obtained on a 64 x 64 matrix by calculating
      the uptake constant per pixel and the cross calibration factor (CF) between the
      SPECT system and a well counter (rCBF = K.CF x 100).

PMID- 1403140
TI  - Radioimmunodetection of occult carcinoembryonic antigen-producing cancer.
AB  - This study evaluates the ability of 111In-labeled anti-carcinoembryonic antigen
      (CEA) monoclonal antibody (Mab) ZCE-025 to detect sites of occult cancer in
      patients with elevated serum CEA who have negative or equivocal CT scans. One
      hundred forty patients suspected of having occult cancer were evaluated. Except
      for elevated CEA levels, all had negative work-ups, including negative or
      inconclusive CT scans. Eighty-two patients (59%) had positive scans and 58 (41%)
      had negative scans. Seventy-five of the 82 patients with positive scans had
      confirmation of at least one Mab-positive lesion (91% positive predictive value).
      Thirty-eight of the 58 patients with negative scans had negative follow-up (66%
      negative predictive value). The Mab scan correctly identified at least one site
      of tumor in 75 of the 95 patients with recurrent or metastatic disease (79%
      sensitivity) and correctly predicted the absence of disease in 38 of 45 patients
      (84% specificity).

PMID- 1403141
TI  - Immunoscintigraphy of colorectal carcinoma and the Loch Ness monster.

PMID- 1403142
TI  - Colon carcinoma immunoscintigraphy by monoclonal anti-CEA antibody labeled with
      gallium-67-aminooxyacetyldeferroxamine.
AB  - Previous experimental results in nude mice showing that radiolabeling the
      monoclonal antibody anti-CEA 35 with 67Ga-aminooxyacetyldeferroxamine could give
      better tumor localization than radioiodination prompted us to initiate the
      present clinical study. The 67Ga-labeled antibody anti-CEA 35 (185 MBq, 0.7-1.7
      mg) was injected preoperatively into 14 patients for colorectal carcinoma
      imaging. The same antibody labeled with 125I (3.7 MBq, 0.25 mg) was injected
      simultaneously to compare the 67Ga and 125I dose recoveries in surgical
      specimens. Twelve of 14 primary tumors gave a positive 67Ga scintigraph. The mean
      %ID/g recovered in all tumors 3-9 days after injection was significantly higher
      for 67Ga (0.019%) than for 125I (0.005%) (p < 0.001, paired t test). The tumor-to
      normal tissue ratios were generally higher for 67Ga, with the exception of liver.
      We conclude that 67Ga-aminooxyacetyldeferroxamine improved immunoscintigraphy
      outside the liver, particularly in the pelvic region. We also show that
      deferroxamine infusion accelerates the excretion of 67Ga in eight patients and
      propose that this could lead to further improvement of immunoscintigraphy.

PMID- 1403144
TI  - Does radiotherapy affect regional bone formation?

PMID- 1403143
TI  - Local and systemic effects of radiation on bone metabolism measured by
      quantitative SPECT.
AB  - Quantitative bone scintigraphy (QBS), which measures 99mTc-MDP uptake expressed
      as percent of injected dose per cc, indicates bone metabolism. It is measured in
      the bones of patients before and after radiation treatment and then compared to
      normal controls. QBS was performed in a group of 22 normal individuals and was
      measured twice, 2-10 mo (mean 4.9) apart. There was no significant difference
      between the two measurements. QBS was performed also in 28 patients before,
      immediately after and at certain time intervals after radiation therapy for
      cancer. Both the irradiated and the nonirradiated bones showed significant
      decreases in bone metabolism at 2-18 mo (mean 8.8) after irradiation. In
      addition, increases and decreases of 99mTc-MDP uptake were similar in the
      irradiated and in the nonirradiated bones, and there were significant
      correlations of the QBS values in the different bones of each individual patient.
      The etiology of the changes in bone metabolism in the nonirradiated bones is not
      yet fully understood, but it appears to be the result of a systemic effect of
      radiation.

PMID- 1403145
TI  - Planar myocardial perfusion imaging with technetium-99m-teboroxime: comparison by
      vascular territory with thallium-201 and coronary angiography.
AB  - Myocardial perfusion agents labeled with 99mTc offer improved physical imaging
      properties compared to 201TI. Teboroxime is a new 99mTc-labeled compound for
      myocardial perfusion imaging that shows a high myocardial extraction and rapid
      clearance. Sixty-seven patients underwent planar teboroxime imaging with a rapid
      acquisition protocol. Agreement of teboroxime and 201TI for the presence or
      absence of disease occurred in 56/65 patients (86%). There was agreement (normal
      or abnormal) between the two agents in 156/195 vessels (80%) and 457/585 segments
      (78%). When abnormal segments (ischemia or infarction) were compared, teboroxime
      showed significantly more ischemic segments (89/135, 66%) than did 201TI (73/135,
      54%, p < 0.05). Teboroxime offers accuracy comparable to 201TI for the diagnosis
      of coronary artery disease and may improve the detection of ischemic or viable
      myocardium. In addition, its rapid myocardial clearance permits stress/rest
      imaging in 60-90 min.

PMID- 1403146
TI  - Brain SPECT and the effect of cerebral angioplasty in delayed ischemia due to
      vasospasm.
AB  - Cerebral vasospasm is a major determinant of outcome after subarachnoid
      hemorrhage (SAH). Brain SPECT with 99mTc-HMPAO was obtained before and after
      cerebral angioplasty in 10 patients with delayed ischemia due to vasospasm. Eight
      patients had clinically evident neurologic improvement after the procedure.
      Visual interpretation and an internal-reference (cerebellum), manual, semi
      quantitative region of interest (ROI) analysis revealed improvement of regional
      cerebral blood flow (rCBF) in 9 out of 10. There were disagreements between the
      visual and ROI analysis in the two that did not improve clinically. For all 10,
      the average increase per anterior circulation vessel dilated (n = 17) was 8.8% by
      comparison of the corticocerebellar ratios. For the eight that improved, the
      average increase was 10.5%. Brain SPECT is valuable for evaluating delayed
      cerebral ischemia caused by vasospasm after SAH and is useful to document the
      changes in rCBF induced by angioplasty. It is possible that SPECT may be useful
      to detect critical reductions in perfusion before clinical deficits develop,
      thereby offering the potential to identify candidates for early treatment with
      angioplasty.

PMID- 1403147
TI  - Parathyroid imaging--current status and future prospects.

PMID- 1403148
TI  - Localization of infection using streptavidin and biotin: an alternative to
      nonspecific polyclonal immunoglobulin.
AB  - Since favorable images of infection are obtained with radio-labeled nonspecific
      IgG, streptavidin has been considered as an alternative protein in this
      investigation. The advantage of streptavidin is that once localized it may be
      targeted with radiolabeled biotin. Studies were conducted in a mouse model with
      an Escherichia coli infection in one thigh. Indium-111-labeled streptavidin
      showed equivalent localization to the infection as that obtained with 111In
      labeled polyclonal nonspecific IgG, however blood levels with streptavidin were
      lower at all time points; consequently, target-to-blood ratios were improved.
      Pretargeting with unlabeled streptavidin followed 3 hr later with 111In-labeled
      biotin showed equivalent localization in the target and reduced activity in all
      organs sampled. As such, infected thigh-to-normal thigh ratios were improved 3
      fold for pretargeting versus either labeled IgG or streptavidin. Improvements in
      infected thigh-to-liver and blood ratios were greater than 8-fold. Only in the
      case of kidneys was the ratio unimproved. In conclusion, we have shown that by
      preadministration of unlabeled streptavidin followed by labeled biotin,
      infectious lesions in a mouse model may be imaged earlier with lower background
      levels relative to the administration of labeled nonspecific IgG.

PMID- 1403149
TI  - New methods for localizing infection: a role for avidin-biotin?

PMID- 1403150
TI  - Comparison of regional blood-brain transport kinetics between glucose and
      fluorodeoxyglucose.
AB  - The fluorodeoxyglucose (FDG) method for estimating regional cerebral glucose
      metabolic rate (LCMRglc) requires that a fixed relationship (the "lumped
      constant") exists between net FDG and glucose (GLC) extraction throughout the
      brain. In addition to the relative rate of metabolism between FDG and GLC, this
      assumed constant is affected by the relative rate of blood-to-brain FDG transport
      compared to that of glucose. However, little data is available regarding the
      regional stability of the FDG versus GLC transport-rate relationship. We
      therefore used high resolution, quantitative dual-tracer digital autoradiography
      to directly compare the blood-to-brain transport rate constants (K1) of
      radiolabeled GLC and FDG in normal and pharmacologically-stimulated rats. The
      rats were given 45 sec terminal intravenous infusions of a mixture of 18F-FDG and
      14C-GLC. Autoradiograms of the brain representing the FDG and GLC tracer
      concentrations were produced, digitized, and converted into digital images of K1.
      We found that the global K1 values of FDG and GLC were not significantly
      different from each other. However, detailed analysis revealed that some
      structures in the normal animals, such as the hippocampus and cerebellum, had
      different quantitative patterns of FDG transport compared to GLC transport. Thus,
      our results indicate that the relationship between GLC and FDG transport is not
      uniform throughout the brain as has previously been assumed. This observation
      suggests that regional variations in the type and distribution of glucose
      transporters may exist and that the fluorodeoxyglucose "lumped constant" may vary
      somewhat among different brain regions.

PMID- 1403151
TI  - A quantitative autoradiographic study of the heterogeneous activity distribution
      of different indium-111-labeled radiopharmaceuticals in rat tissues.
AB  - In light of the increased interest in small scale dosimetry, this paper presents
      a quantitative autoradiographic method for evaluation of heterogeneous activity
      distribution in tissues. This was studied in rat tissues after administration of
      111In-chloride, -oxine, -tropolone, 111In-labeled homologous blood cells and
      111In-anti-CEA-F(ab')2, using quantitative whole-body autoradiography.
      Quantification was performed utilizing an image analyzing system designed for
      whole-body autoradiographs. Very heterogeneous activity distribution was found in
      several tissues including the liver, spleen, kidneys, bone marrow, lymph nodes
      and testes. Notable was the high 111In uptake in organs characterized as rapidly
      proliferating, and known to have numerous transferrin receptors. In the
      gastrointestinal tract, all activity was associated with the intestinal walls.
      The heterogeneous tissue distribution shown in this investigation accentuates the
      necessity for performing detailed studies of the tissue distribution of
      radiopharmaceuticals. This is especially important for the radiation dosimetry of
      radionuclides emitting beta-particles or low energy electrons. We suggest whole
      body autoradiography as an excellent implement to determine local activity
      concentrations in organs and tissues necessary for accurate absorbed dose
      calculations.

PMID- 1403152
TI  - Quantitative autoradiography for the study of radiopharmaceutical uptake and dose
      heterogeneity.

PMID- 1403153
TI  - Technetium-99m-N1-(2-mercapto-2-methylpropyl)-N2-(2-propargylthio-2-
      methylpropyl)-1,2-benzenediamine (T691): preclinical studies of a potential new
      tracer of regional cerebral perfusion.
AB  - We report in vitro and in vivo preclinical studies of a new cerebral blood flow
      tracer, [99mTc]N1-(2-mercapto-2-methyl-propyl)-N2-(2- propargylthio-2
      methylpropyl)-1,2-benzenediamine (T691). The tracer demonstrates excellent in
      vitro chemical stability and accumulates regionally in the brain in a pattern
      consistent with that of cerebral blood flow. First-pass cerebral extraction
      determined with the use of the brain uptake index method in the rat was 0.76.
      Bolus intracarotid injection in monkeys indicated a cerebral extraction of 68%
      and prolonged retention of 67% of the initially extracted activity.
      Autoradiographic studies in rats revealed a pattern characteristic of cerebral
      blood flow at both 1 and 60 min after systemic injection. Dynamic tomographic
      imaging following systemic injection in the monkey revealed peak brain activity 1
      to 2 min postinjection, without significant decline over 60 min. Chromatographic
      studies of brain as long as 60 min following systemic injection of [99mTc]T691
      showed no evidence of tracer metabolism to account for its retention. Overall,
      [99mTc]T691 demonstrates promise as a potential new clinical tracer of cerebral
      perfusion.

PMID- 1403154
TI  - Mapping cerebral blood flow.

PMID- 1403155
TI  - Major upward creep of the heart during exercise thallium-201 myocardial SPECT in
      a patient with chronic obstructive pulmonary disease.
AB  - We report on a patient in whom we observed an unusually important upward creep of
      the heart on postexercise 201TI tomographic acquisition. When uncorrected, this
      led to reconstruction of grossly abnormal tomograms, which were normal after
      correction of upward creep of the heart. This phenomenon may be related to the
      patient's history of chronic obstructive pulmonary disease. Special attention
      should be given to upward creep artifact in such pulmonary diseases.

PMID- 1403156
TI  - Pelvic radioiodine uptake in a rectal wall teratoma after thyroidectomy for
      papillary carcinoma.
AB  - A 30-yr-old woman with previously resected papillary thyroid carcinoma was found
      to have a pelvic lesion which concentrated radioiodine. By performing
      simultaneous 131I whole-body and 99mTc-methylene diphosphonate bone scans, we
      found the lesion to be in soft tissue between the sacrum and bladder. Radioiodine
      therapy was postponed so that the lesion, a benign teratoma of the rectal wall,
      could be surgically removed. Prior to laparotomy, the patient received a second
      tracer dose of 131I so that the lesion could be located at surgery with a hand
      held gamma detector. A postoperative whole-body 131I scan confirmed that the
      lesion had been removed, thus reducing the absorbed radiation that would have
      been received by the ovaries during radioiodine therapy. Although the lesion
      contained both thyroid and gastric epithelium, accumulated 131I was limited to
      the area with thyroid follicles.

PMID- 1403157
TI  - Gallium-67-citrate scanning in patients with sarcoid uveitis.
AB  - Gallium-67-citrate is useful for characterizing activity in patients with
      sarcoidosis. Gallium-67 uptake in bilateral symmetrical hilar lymphadenopathy
      and/or symmetrical salivary glands is typical of this clinical entity.
      Sarcoidosis is a systemic disease, and uveitis is considered the hallmark of
      ophthalmic sarcoidosis. We present two cases of ophthalmic sarcoidosis that shows
      uveal accumulation of 67Ga-citrate associated with clinical symptoms.

PMID- 1403158
TI  - Thallium-201 accumulation by epidermoid inclusion cyst.
AB  - An elderly male undergoing re-evaluation for coronary artery disease demonstrated
      an extra-cardiac focus of 201Tl accumulation during the performance of a planar
      myocardial perfusion scan. This corresponded to a subcutaneous lesion of the left
      posterior thorax found on a concurrent computerized axial tomographic (CAT) scan
      and upon surgical excision proved to be an "epidermoid inclusion cyst." A follow
      up nuclear scan failed to reveal any residual extracardiac tracer localization.
      Confusing this lesion with metastatic deposits during 201Tl neoplastic
      evaluations can be avoided by examination of the adjacent integument.

PMID- 1403159
TI  - Sensitivity, resolution and image quality with a multi-head SPECT camera.
AB  - This investigation sought to determine which collimation factors were most
      important in providing superior image quality with a three-headed SPECT device.
      The relationship between sensitivity, resolution and SPECT image quality was
      studied. Two different sets of parallel-hole collimators were used. The ultrahigh
      resolution collimators have higher spatial resolution (8.9 versus 11.0 mm), but
      only 55% of the sensitivity of the high-resolution collimators. A phantom with
      hot rods was imaged with both collimator sets. Observers compared images with the
      ultrahigh-resolution collimators to images of varying counts with the high
      resolution collimators and determined which high-resolution images matched the
      ultrahigh-resolution images in image quality. Eleven patient studies were
      acquired with both collimator sets for equal time, and observers chose which
      image set they preferred. Transverse images of brain and liver studies were
      simulated with varying resolution and counts and subjectively compared. The
      phantom study indicated that the improvement in resolution led to image quality
      comparable to increasing the number of counts by a factor of 2.5 to 3.4. The
      clinical studies showed that the ultrahigh-resolution collimators were preferred
      in a large majority of the cases. These trends were also seen in the simulation
      study. These results confirm that higher resolution collimators should be used
      with multihead SPECT devices. The improvement in resolution more than compensates
      for the loss in sensitivity, leading to an overall improvement in image quality.

PMID- 1403160
TI  - Fatty acid kinetics in aerobic myocardium: characteristics of tracer carbon entry
      and washout and influence of metabolic demand.
AB  - These studies evaluated the kinetics of tracer uptake and washout after step
      function labeling with 14C-palmitate. Washout and uptake function curve analysis
      for total radioactivity (TR) was derived according to the expressions: TR = Fx
      integral of 0 infinity C(t) x dt and TR = Fx integral of 0 infinity (Css - C(t))
      x dt, respectively, with Vc = TR/Ca, where F = coronary flow; Css = steady-state
      concentration; C(t) = concentration with respect to time; Ca = arterial
      concentration; and Vc = distribution volumes within the fatty acid pathway. The
      only radioactive metabolites in venous effluent were fatty acids and 14CO2. The
      estimated Vc of fatty acids was small (1.2-1.7 ml/g dry wt or 0.4-0.5 mumol/g dry
      wt) and compatible with labeled substrate trapped in the blood volume. The Vc of
      14CO2 was much larger (11.4-15.8 ml/g dry wt or 3.6-4.2 mumol/g dry wt) and
      correlated with counts contained in the aqueous soluble and fatty acid fractions
      in tissue. The counts in tissue were distributed between the aqueous soluble
      fraction (40%), which was rapidly depleted during washout, and a lipid fraction
      (60%) (triacylglycerols and phospholipids), which was resistant to washout.
      Distributions in tissue radioactivity between the aqueous soluble and lipid
      fractions support the notion of a dual pathway in fatty acid oxidation, one arm
      of which passes through the resident pool of triacylglycerols, which has a long
      time constant. The presence of this pool may impart an error in estimating fatty
      acid oxidation by external labeling techniques.

PMID- 1403161
TI  - Correction for attenuation in technetium-99m-HMPAO SPECT brain imaging.
AB  - We present a correction technique that uses the effective bone and tissue
      attenuation coefficients to compensate 99mTc-HMPAO brain SPECT projections for
      attenuation. Transverse images of a human skull filled with a uniform mixture of
      99mTc and gelatin have a greater count density at the center with respect to the
      periphery when corrected for attenuation with the effective water/tissue
      coefficient of 0.12 cm-1. An attenuation coefficient of 0.09 cm-1 produces
      uniform images at the expense of a reduced count density. Additional experiments
      with phantoms wrapped with aluminum (to simulate bone) indicate that the greater
      count density at the image center is a result of increased attenuation at the
      edges of the projections where there is a greater path length through the
      aluminum (or bone). SPECT projections explicitly corrected for both bone and soft
      tissue attenuation result in images of improved uniformity and increased count
      density.

PMID- 1403163
TI  - Functional brain SPECT: the emergence of a powerful clinical method.

PMID- 1403162
TI  - Description of a prototype emission-transmission computed tomography imaging
      system.
AB  - We have developed a prototype imaging system that can perform simultaneous x-ray
      transmission CT and SPECT phantom studies. This system employs a 23-element high
      purity-germanium detector array. The detector array is coupled to a collimator
      with septa angled toward the focal spot of an x-ray tube. During image
      acquisition, the x-ray fan beam and the detector array move synchronously along
      an arc pivoted at the x-ray source. Multiple projections are obtained by rotating
      the object, which is mounted at the center of rotation of the system. The
      detector array and electronics can count up to 10(6) cps/element with sufficient
      energy-resolution to discriminate between x-rays at 100-120 kVp and gamma rays
      from 99mTc. We have used this device to acquire x-ray CT and SPECT images of a
      three-dimensional Hoffman brain phantom. The emission and transmission images may
      be superimposed in order to localize the emission image on the transmission map.

PMID- 1403164
TI  - Predictive value of dipyridamole thallium imaging in a patient with myocardial
      bridging but without fixed obstructive coronary artery disease.
AB  - Both dipyridamole and exercise-201Tl imaging are sensitive, specific and of
      prognostic value in patients with suspected coronary artery disease, following
      myocardial infarction, and undergoing major noncardiac surgery. Though reported
      sensitivities and specificities vary widely from 60% to 100%, the consensus is
      that both are between 80% and 90% for both dipyridamole and exercise studies
      (23). Moreover, when compared directly in the same study populations, the two
      have equal sensitivities and specificities (9,11,13,23). Transient thallium
      perfusion abnormalities are the most consistent predictors of adverse cardiac
      events and have more predictive power than clinical and angiographic parameters.
      Thallium reversibility may be a better predictor of adverse cardiac events than
      angiography since it represents more of a physiologic rather than a purely
      anatomic evaluation of the heart. It is difficult to make an exact comparison of
      some of the studies in the literature because they use different patient
      populations, sometimes define coronary stenosis in different ways, may have
      different cardiac endpoints and may not differentiate between reversible and
      fixed thallium perfusion defects. Exercise has the advantage of a graded
      examination and more experience historically and is of importance in a detailed
      study of cardiopulmonary hemodynamics, as in cardiac transplantation.
      Dipyridamole is more useful in patients who cannot achieve symptom-limited,
      submaximal exercise. It may also be more useful for patients who are bedridden or
      have peripheral vascular disease. Angina occurs less frequently with
      dipyridamole.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403165
TI  - Application of a continuous ventricular function monitor with miniature cadmium
      telluride detector to patients with coronary artery bypass grafting.

PMID- 1403166
TI  - Reconstitution and fractionation of radiopharmaceutical kits.

PMID- 1403167
TI  - Calculation of the radiation dose at a bone-to-marrow interface.

PMID- 1403168
TI  - Recirculation subtraction and left-to-right shunt quantitation.

PMID- 1403169
TI  - Clinical epidemiology. Applying science to the art of nurse-midwifery.

PMID- 1403170
TI  - The National Birth Center Study. Part I--Methodology and prenatal care and
      referrals.
AB  - This is the first of three articles that will report on the complete findings
      from the National Birth Center Study (NBCS). This article describes the study
      methodology, compares the entire group of NBCS subjects with all women who gave
      birth in the United States in 1986, describes the prenatal care and prenatal
      referral practices of birth centers in the study, and describes the women who
      were admitted to the birth centers for intrapartum care with regard to
      characteristics known or thought to be associated with perinatal risk. Nearly
      18,000 women were included in the study; two-thirds of them (n = 11,814) were
      admitted to the birth centers for intrapartum care. Although medical and
      obstetric complications were the most common reason for discontinuing birth
      center care, they accounted for less than half of the women who were not admitted
      to the birth centers for labor and delivery; many women left for a variety of
      other reasons. In addition to describing birth center clients, birth center care
      providers, and birth center care, the NBCS provides detailed information about
      the characteristics and experiences during pregnancy of a large population of
      essentially low-risk women receiving a low-intervention style of maternity care.

PMID- 1403171
TI  - Acupuncture and related treatment modalities. Part I: Theoretical background.
AB  - An introduction to the therapeutic applications, history, and theory of
      acupuncture and several related treatment modalities is presented. The practices
      of acupuncture, moxibustion, acupressure, and shiatsu are described. The
      underlying concept of treatment of imbalances of ch'i, or life energy, is
      presented along with the flow of ch'i in meridians (pathways), and the theories
      of yin and yang, Five Elements, and Eight Principle Patterns.

PMID- 1403172
TI  - Acupuncture and related treatment modalities. Part II: Applications to antepartal
      and intrapartal care.
AB  - The application of acupuncture, moxibustion, acupressure, and shiatsu to
      antepartal and intrapartal care are discussed. Information on therapeutic
      interventions as described in textbooks is presented and compared with specific
      treatments evaluated in research studies. Specific clinical indications addressed
      include nausea during pregnancy, repositioning of the fetus in breech position,
      stimulation of contractions and true labor, and pain relief in labor.
      Qualifications for practitioners and recommendations for certified nurse-midwives
      caring for clients seeking referral for these services are discussed.

PMID- 1403174
TI  - ACNM-accredited nurse-midwifery education programs. Program information.

PMID- 1403173
TI  - Prevalence of abuse among pregnant women choosing certified nurse-midwife or
      physician providers.
AB  - Despite the fact that violence against women is a widespread problem in the
      United States, many providers do not routinely screen for it, particularly if the
      woman is not from a lower socioeconomic group. This was a secondary analysis of
      survey data from 940 antenatal women in private CNM and MD practices. Median
      annual income was $40,000 to $49,000 and mean schooling completed was 15 years.
      It was found that 91 (9.7%) had a history of previous abuse and eight (0.9%) were
      currently in an abusive relationship. Women with a previous history of abuse were
      found in the CNM caseloads at higher than expected levels. Annual income was
      predictive of women currently being abused, but not for women with past history.
      Abused women had on average less education than nonabused, with the most marked
      difference seen in women reporting current abuse. These results provide further
      evidence that the problem of abuse is not restricted to women of lower
      socioeconomic status. The finding that women with history of abuse were more
      likely to appear in CNM caseloads adds further support to the need for routine
      screening.

PMID- 1403175
TI  - Evaluation of research studies. Part I: Randomized trials.
AB  - Clinical practice is often based on the results of research. Critical evaluation
      of research studies is important if appropriate conclusions are to be drawn. In
      this series of columns, we review principles of research methodology and
      statistical analysis. Our intent is to assist certified nurse-midwives in
      understanding the relative merits of the research they read and use. This
      article, the first of the series, will review issues pertinent to randomized
      clinical trials.

PMID- 1403176
TI  - Nurse-midwifery and the first Tuesday in November.

PMID- 1403177
TI  - The National Birth Center Study. Part II--Intrapartum and immediate postpartum
      and neonatal care.
AB  - Part II of a three-part report of the National Birth Center Study describes care
      provided to 11,814 women and their newborns during and after labor and delivery
      until they were transferred or discharged from the birth centers. There were few
      low birth weight or preterm or postterm births, but more macrosomic babies than
      among all U.S. births during the same time period. Certified nurse-midwives
      provided most of the intrapartum care, which is described in the context of
      medically recommended standards and data that describe care provided to low-risk
      women giving birth in U.S. hospitals. Birth center care deviated from typical
      hospital care in several ways. Birth center clients were much less likely to
      receive central nervous system depressants, anesthesia, continuous electronic
      fetal monitoring, induction and/or augmentation of labor, intravenous infusions,
      amniotomies, or episiotomies, and they had relatively few vaginal examinations.
      They were more likely to eat solid food during labor and to take showers and/or
      baths. Nulliparity was strongly associated with longer first stage labors and
      longer labor was associated with more frequent use of many kinds of
      interventions. Infant birth weight, mother's position during delivery, and
      forceps- or vacuum-assisted deliveries are examined in relation to episiotomies
      and lacerations and tears.

PMID- 1403178
TI  - In-hospital care for low-risk childbirth. Comparison with results from the
      National Birth Center Study.
AB  - The largest prospective study of freestanding birth centers was reported in 1989.
      This article reports on data from a comparison group of over 2,000 low-risk women
      who were admitted to hospital-care settings during the same period. The data on
      the hospitalized women were collected using the research methodology and data
      collection instruments developed for the birth center study. Consequently, these
      data offer the opportunity to observe differences that can be associated with
      birth site. Both groups of women experienced similar rates of serious antepartum
      and intrapartum health problems and maternal morbidity. However, even when
      controlling for complications and differences in sociodemographic
      characteristics, women in hospitals were more likely to receive an interventive
      style of labor and birth management. Neonatal outcomes were also similar,
      although the incidence of sustained fetal distress, prolapsed cord, and
      difficulty in establishing respirations were significantly greater in the
      hospital sample. Hospital care did not offer any advantage for women at lowest
      risk, and it was associated with increased intervention. The results of this
      study provide support for the National Birth Center Study's conclusion that birth
      centers offer a safe and acceptable alternative for selected pregnant women.

PMID- 1403179
TI  - Nurse-midwifery care to vulnerable populations. Phase I: Demographic
      characteristics of the National CNM Sample.
AB  - The purpose of this article is to describe the extent to which certified nurse
      midwives (CNMs) provide care to vulnerable populations in the United States and
      the source of reimbursement for this care. The data were obtained from the first
      phase of a national study to address the characteristics of women served and cost
      of care provided by CNMs. Results were analyzed nationally and by American
      College of Nurse-Midwives regions. Certified nurse-midwives in all types of
      practices are providing care to women from populations that are vulnerable to
      poorer than average outcomes of childbirth because of age, socioeconomic status,
      refugee status, and ethnicity. Ninety-nine percent of CNMs report serving at
      least one group of vulnerable women, and CNMs in the inner city and rural
      practices serve several groups. The vast majority of CNMs are salaried; only 11%
      receive their primary income from fee-for-service. Fifty percent of the payment
      for CNM services is from Medicaid and government-subsidized sources whereas less
      than 20% comes from private insurance. Source of income varies by type of setting
      in which the CNM attends births. The results suggest that CNMs, as a group, make
      a major contribution to the care of vulnerable populations.

PMID- 1403181
TI  - Use of folic acid supplementation in the periconceptional period provides great
      promise for the primary prevention of the neural tube defects (NTDs),
      anencephaly, and spina bifida.

PMID- 1403180
TI  - MIDIRS has set up the world's first computer midwifery data base.

PMID- 1403182
TI  - The effects of the birth setting on fetal mortality.

PMID- 1403183
TI  - Infant circumcision.

PMID- 1403185
TI  - Birthing centers in Michigan.

PMID- 1403184
TI  - Infant circumcision.

PMID- 1403186
TI  - Educational requirements for advanced practice for nurse-midwives.

PMID- 1403188
TI  - Investigation of an occupational cancer cluster using a population-based tumor
      registry and the National Death Index.
AB  - Occupational physicians investigate perceived cancer clusters to alleviate
      employee concerns and pursue etiologic hypotheses. We conducted a retrospective
      cohort analysis of all past and present employees of a metal fabrication plant
      and a comparison plant after employees recognized five cancer cases in 1987. We
      ascertained cases of all subjects who were employed at some time in the 8 years
      before 1987 through the Colorado Central Cancer Registry and determined vital
      status through the National Death Index. Cancer incidence at the index plant was
      almost identical to that of the population of the Denver metropolitan area
      (standardized incidence ratio [SIR] = 99, 95% confidence interval [CI] 59-165).
      Proportional incidence ratios revealed that no type of cancer occurred with
      significant excess in the index plant population during 1979 through 1986. Where
      population-based tumor registries exist, occupational physicians can employ this
      inexpensive and robust methodology to assess cancer incidence in exposed cohorts,
      pursue exposure-response relations, and evaluate clusters.

PMID- 1403187
TI  - Occupational risks for nasopharyngeal cancer in Shanghai.
AB  - To investigate occupational determinants of nasopharyngeal cancer (NPC) in the
      urban area of Shanghai, occupational information for 996 incident NPC patients
      diagnosed during 1980 to 1984 was compared with 1982 census data on employment.
      Standardized incidence ratios for NPC were estimated for broad and detailed
      occupational classifications. For the broadest level of classification, no excess
      risk was observed among craftmen and related manufacturing workers, but within
      this group significant excess risks were observed for specific occupations of
      textile weavers and knitters; metal smelting, converting, and refining
      furnacemen; boiler firemen; blacksmiths, hammersmiths, and forging-press
      operators; bakers, pastry cooks, and confectionery makers; welders and flame
      cutters; and metal grinders, polishers, tool sharpeners, and machine-tool
      operators. Some of these findings are new; others are consistent with previous
      studies in other areas of the world. This study provides further evidence for the
      role of occupational factors in NPC.

PMID- 1403189
TI  - Factors affecting plasma aluminum concentrations in nonexposed workers.
AB  - In this study, the distribution and determinants of plasma aluminum
      concentrations were examined in 71 office employees not occupationally exposed to
      aluminum. The samples were analyzed by Zeeman graphite furnace atomic absorption
      spectroscopy and were found to be log normally distributed. After using the
      International Federation of Clinical Chemistry (IFCC) recommended procedure for
      removal of likely aberrant values, the 95th percentile value was 198 nmol/L (90%
      CI:165-238); when those using antacids were also excluded, the 95th percentile
      value fell to 175 nmol/L (90% CI:147-208). Multiple regression analysis indicated
      that the factors most predictive of log plasma aluminum were the batch in which
      the sample was analyzed and the use of antacids containing aluminum. The
      statistical significance of the batch variable likely indicates the well
      recognized problem of contamination in sampling and analyzing aluminum.

PMID- 1403190
TI  - Absence experience of career firefighters reaching mandatory retirement age.

PMID- 1403191
TI  - Computer-specific spectacle lens design preference of presbyopic operators.
AB  - Twenty-nine presbyopic subjects who spent at least 20 hours a week at a video
      display terminal compared a progressive addition lens designed for this function,
      with another commonly prescribed task-specific lens. Each of the paired lens
      types was worn for 4 weeks and then compared directly for 1 week. A statistically
      significant (P < .05) portion of the subjects (76%) preferred the task-specific
      lenses overall. It also was preferred more frequently for each feature compared,
      although the difference was statistically significant (P < .05) only for utility
      of distance vision. Both of the task-specific designs contributed to symptomatic
      relief. The presence of a distance-clear zone and the absence of lens
      discontinuities most likely account for user preference for the task-specific
      lenses. That preference suggests improved performance for presbyopic computer
      users wearing task-specific progressive addition lenses.

PMID- 1403192
TI  - ACOEM position statement on residential radon exposure. American College of
      Occupational and Environmental Medicine.

PMID- 1403193
TI  - Does fibromyalgia qualify as a work-related illness or injury?

PMID- 1403194
TI  - Critique of Neumark's estimate of costs of occupational injury and illness.

PMID- 1403196
TI  - Development of a library-based information service for the subject of workers'
      compensation: a proposal.

PMID- 1403197
TI  - Comprehensive medical examinations are optional.

PMID- 1403195
TI  - A study of the detailed circumstances of 'sharps' injuries in health care
      workers.

PMID- 1403198
TI  - Definition, sources, magnitude, effect modifiers, and strategies of reduction of
      the healthy worker effect.
AB  - This article summarizes, compares, and contrasts the definition, sources,
      magnitude, effect modifiers, and strategies of reduction of the healthy worker
      effect (HWE), based on the opinion expressed in the papers of nine contributors
      who responded to the request of the Industrial Disease Standards Panel (IDSP),
      Ontario, Canada. It provides an insight into the complex issues relating to the
      HWE. In addition, the catalog of 15 strategies to reduce the HWE is deemed to be
      useful for investigators in occupational epidemiology.

PMID- 1403199
TI  - IgG subclass antibody against trimellitic anhydride in workers with and without
      immunologic lung diseases.
AB  - In a retrospective comparison of two worker cohorts with elevated total antibody
      against trimellitic anhydride (TMA) conjugated to human serum albumin (TM-HSA),
      IgG subclass antibodies against TMA were studied in 19 workers with and 12
      workers without TMA-induced immunologic lung disease. The main outcome measures
      were ELISA index of IgG1, IgG2, IgG3, and IgG4 against TM-HSA. There were no
      statistically significant differences in levels of any IgG subclass between these
      two groups. Neither were there any statistically significant differences when
      workers without lung disease were compared with subgroups of workers with lung
      disease, such as late respiratory systemic syndrome (n = 8), asthma/rhinitis (n =
      6), or both (n = 5). In TMA workers with elevated total antibody against TM-HSA,
      IgG subclasses against TM-HSA in workers with TMA-induced immunologic lung
      disease were not different from workers without disease.

PMID- 1403200
TI  - Ethnographic explanations for the clustering of attendance, injury, and health
      problems in a heavy machinery assembly plant.
AB  - We examine the clustering of attendance, illness, and accidental injury problems
      in a large unionized manufacturing plant using both quantitative and qualitative
      methods. We find that the distribution of workers into problem groups is related
      to 1) conflicts over seniority, 2) physical stressors and their influence on
      perceived desirability of certain kinds of jobs, and 3) organizational conditions
      and environments congenial to the development of distinct occupational
      "subcultures." We suggest that the case study approach we apply in this paper is
      critical to the design of programs of preventive intervention and complements the
      more commonly applied multiple-site and individually focused, survey approaches.

PMID- 1403202
TI  - Diagnosing sinusitis by X-ray: is a single Waters view adequate?
AB  - OBJECTIVE: To determine whether a single Waters view (occipito-mental) radiograph
      could be substituted for a four-view sinus series to diagnose sinusitis, and to
      determine the inter- and intraobserver variabilities for sinus radiography.
      DESIGN: Radiographs were interpreted by radiologists blinded to the clinical
      history, and results were recorded on a standardized form. SETTING: Veterans
      Affairs Medical Center. PARTICIPANTS: Staff attending radiologists, an attending
      radiologist with special training in skull radiology, and a senior radiology
      resident. MEASUREMENTS AND MAIN RESULTS: The agreement between the Waters view
      and the four-view sinus series was moderate to substantial (simple agreement = 75
      84%, kappa = 0.5-0.68). However, agreement varied by sinus and, after correction
      for chance agreement, was substantial only for the maxillary sinuses (kappa =
      0.72-0.87). Intraobserver agreement (kappa = 0.72-0.84) was superior to
      interobserver agreement (kappa = 0.49-0.59) for the four-view sinus series.
      CONCLUSIONS: Substituting a single Waters view for a four-view sinus series may
      be an acceptable strategy for diagnosing maxillary sinusitis.

PMID- 1403201
TI  - Achieving consensus on withdrawing or withholding care for critically ill
      patients.
AB  - OBJECTIVE: To examine the decision-making process to withhold or stop life
      support. DESIGN: Survey. SETTING: Medical intensive care unit of a tertiary care
      center. PARTICIPANTS: Physicians and families of 15 critically ill patients; in
      seven cases patients also participated. MEASUREMENTS: Meetings between physicians
      and family members concerning a decision to withhold or stop treatment of a
      critically ill family member were tape-recorded. Transcriptions of the meetings
      were analyzed for 1) process: how the physician introduced the need for a
      decision, framed the likely outcomes of options, and closed on a decision; 2)
      what decision was made; and 3) the outcome; died, discharged home, or discharged
      to another institution. RESULTS: The concept of "patient's wishes" was a central
      orientation point for the negotiation of consensus regarding withholding or
      withdrawing therapy even when the patient was not a participant. Physicians
      tended to provide a direct and unambiguous introduction, give equal weights to
      options during decision framing, but narrow the options during decision closure
      to correspond to their judgments. Not every decision was consistent with the
      physician's judgment. CONCLUSIONS: Decision making to withhold or withdraw life
      support therapy from critically ill persons involves complex, difficult
      processes. Successful management of the tension among life extension, quality of
      life, patient autonomy, and social justice requires better understanding of these
      processes.

PMID- 1403203
TI  - Utilization of medical services for the treatment of acute low back pain:
      conformance with clinical guidelines.
AB  - OBJECTIVE: To assess the utilization of diagnostic and therapeutic medical
      services for the management of acute low back pain in a primary care setting, and
      to determine whether such utilization conforms to suggested guidelines for the
      management of this condition. STUDY DESIGN: A retrospective chart audit of
      consecutive cases of acute low back pain. Specific elements of the diagnostic and
      therapeutic approach were judged appropriate or inappropriate based on comparison
      with published recommendations supported by the medical literature. SETTING: The
      primary care adult practice of a university-affiliated health maintenance
      organization. PATIENTS: One hundred eighty-three patients presenting with acute
      low back pain of musculoskeletal origin. MEASUREMENTS AND MAIN RESULTS: According
      to suggested guidelines for the care of acute low back pain, 26% of plain lumbar
      x-rays (10/38), 66% of computed tomography (CT) and magnetic resonance imaging
      (MRI) scans (12/18), and 82% (23/28) of subspecialty referrals were categorized
      as inappropriate. Among patients without indications for these services, 12%
      (10/85) had received lumbar x-rays, 7% (12/168) had received lumbar MRI or CT
      scans, and 14% (23/168) had received subspecialty referrals. Underutilization of
      these services had occurred in 71% (70/98) of patients with an indication for
      plain lumbar radiography, and 47% (7/15) of patients with potential indications
      for surgical referral or CT/MRI scanning. Neither overutilization nor
      underutilization had led to adverse outcomes or delays in diagnosis in this small
      sample. CONCLUSIONS: According to guidelines from the medical literature, the
      primary care physicians in this study both overutilized and underutilized
      diagnostic and referral services in cases of acute low back pain. It is necessary
      to determine whether underutilization of plain lumbar radiography adversely
      affects diagnostic accuracy and whether overutilization of other services
      improves important clinical outcomes, given the generally benign natural history
      of this condition.

PMID- 1403204
TI  - Placing patients in the queue for coronary surgery: do age and work status alter
      Canadian specialists' decisions?
AB  - OBJECTIVE: To determine the effects of age and work status on whether and where
      cardiovascular specialists would place hypothetical patients in the queue for
      coronary surgery. MATERIALS AND METHODS: Mailed survey presenting a set of
      clinical scenarios either to be rated on a scale with 7 time frames for urgency
      of need or to be designated as questionable/inappropriate for intervention. The
      basic scenario was a patient with mild-moderate stable angina, good left
      ventricular function, and limited coronary disease; operative risks and stress
      test results were varied. Three identifiers were used: "45-year-old civil servant
      gainfully employed"; "45-year-old laborer disabled by angina, faces job loss";
      and "75-year-old retiree, angina limits golf." PARTICIPANTS: Cardiologists and
      cardiac surgeons practicing in five Ontario medical centers (n = 120). RESULTS:
      There was a 59% response rate (120 usable responses). Large shifts in willingness
      to intervene occurred in favor of the disabled laborer (p less than 0.0001) and
      against the retiree (p-value ranges from 0.04 to less than 0.0001, depending on
      operative risk and stress test results), but not for the employed civil servant.
      Striking effects (p less than 0.0001) were also evident in ratings of waiting
      time, with the order of priority being the disabled laborer first, the civil
      servant second, and the retiree last. The overall mean shift due to work status
      or age was equal to, or larger than, the mean shift due to clinical factors, such
      as stress test results, changes in severity of stable angina, and extent of
      coronary disease. CONCLUSION: Cardiovascular specialists may place considerable
      weight on age and work status in determining urgency and appropriateness of
      coronary revascularization. Risk-benefit concerns may partly explain shifting
      thresholds for intervention, but not differential waiting times. The influence of
      these factors should be sought in utilization audits and addressed from an
      ethical perspective.

PMID- 1403205
TI  - How well do faculty evaluate the interviewing skills of medical students?
AB  - OBJECTIVE: To study the reliability and validity of using medical school faculty
      in the evaluation of the interviewing skills of medical students. DESIGN: All
      second-year University of North Carolina medical students (n = 159) were observed
      interviewing standardized patients for 5 minutes by one of eight experienced
      clinical faculty. Interview quality was assessed by a faculty checklist covering
      questioning style, facilitative behaviors, and specific content. Twenty-one
      randomly chosen students were videotaped and rated: by the original rater as well
      as four other raters; by two nationally recognized experts; and according to
      Roter's coding dimensions, which have been found to correlate strongly with
      patient compliance and satisfaction. SETTING: Medical school at a state
      university in the southeastern United States. PARTICIPANTS: Faculty members who
      volunteered to evaluate second-year medical students during an annual Objective
      Structured Clinical Exam. INTERVENTIONS: Interrater reliability and intrarater
      reliability were tested using videotapes of medical students interviewing a
      standardized patient. Validity was tested by comparing the faculty judgment with
      both an analysis using the Roter Interactional Analysis System and an assessment
      made by expert interviewers. MEASUREMENTS AND MAIN RESULTS: Faculty mean
      checklist score was 80% (range 41-100%). Intrarater reliability was poor for
      assessment of skills and behaviors as compared with that for content obtained.
      Interrater reliability was also poor as measured by intraclass correlation
      coefficients ranging from 0.11 to 0.37. When compared with the experts, faculty
      raters had a sensitivity of 80% but a specificity of 45% in identifying students
      with adequate skills. The predictive value of faculty assessment was 12%.
      Analysis using Roter's coding scheme suggests that faculty scored students on the
      basis of likability rather than specific behavioral skills, limiting their
      ability to provide behaviorally specific feedback. CONCLUSIONS: To accurately
      evaluate clinical interviewing skills we must enhance rater consistency,
      particularly in assessing those skills that both satisfy patients and yield
      crucial data.

PMID- 1403206
TI  - Factors affecting the reliability of ratings of students' clinical skills in a
      medicine clerkship.
AB  - OBJECTIVE: To determine the overall reliability and factors that might affect the
      reliability of ratings of students' clinical skills in a medicine clerkship.
      DESIGN: A nine-item instrument was used to evaluate students' clinical skills.
      Raters were also asked to provide a grade of each student's overall clinical
      performance. Generalizability studies were performed to estimate the reliability
      of the ratings. The effects of rater experience and clerkship setting were
      investigated by regression analysis. SETTING: Teaching hospitals and community
      based sites in three Northwestern states. PARTICIPANTS: All students (328) who
      had completed the 12-week clerkship in internal medicine at one medical school
      during the academic years 1987-1989. Raters included attending physicians, chief
      residents, and other residents. RESULTS: Seven observations were needed to
      provide a reliable rating of the overall clinical grade. More observations were
      needed to obtain reliable ratings for individual items, ranging from seven
      observations needed for the rating of data gathering skills to 27 observations
      needed for the rating of interpersonal relationships with patients. Rater
      experience and clerkship setting (i.e., teaching hospitals vs. community-based
      clinics) were found, in general, not to affect significantly the ratings received
      by students. CONCLUSIONS: Reliable ratings of students' overall clinical skills,
      including overall clinical grades, can be achieved by collecting a minimum of
      seven observations. More observations are needed to measure reliably the
      interpersonal aspects of clinical performance. These findings support the use of
      performance ratings to evaluate clinical skills and knowledge of students in
      clerkship settings.

PMID- 1403207
TI  - Dietary counseling of hypercholesterolemic patients by internal medicine
      residents.
AB  - OBJECTIVE: To assess the knowledge, attitudes, and practices of internal medicine
      residents concerning dietary counseling for hypercholesterolemic patients.
      DESIGN: Cross-sectional, self-administered questionnaire survey. SETTING: Survey
      conducted August 1989 in seven internal medicine residency programs in four
      southeastern and middle Atlantic states. PARTICIPANTS: All 130 internal medicine
      residents who were actively participating in outpatient continuity clinic.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only 32% of the residents
      felt prepared to provide effective dietary counseling, and only 25% felt
      successful in helping patients change their diets. Residents had good scientific
      knowledge, but the degree of practical knowledge about dietary facts varied.
      Residents reported giving dietary counseling to 58% of their hypercholesterolemic
      patients and educational materials to only 35%. Residents who felt more self
      confident and prepared to counsel reported more frequent use of effective
      behavior modification techniques in counseling. Forty-three percent of residents
      had received no training in dietary counseling skills during medical school or
      residency. CONCLUSION: Internal medicine residents know much more about the
      rationale for treatment for hypercholesterolemia than about the practical aspects
      of dietary therapy, and they feel ineffective and ill-prepared to provide dietary
      counseling to patients.

PMID- 1403209
TI  - Home visits in a rural office practice: clinical spectrum and effect on
      utilization of health care services.
AB  - OBJECTIVE: To describe the clinical features of home visits and their role in
      continuity of care, costs, and benefits in a rural office practice. DESIGN:
      Prospective study of all home visits performed during a 26-month period. SETTING:
      A general medicine teaching office practice located in rural Virginia. PATIENTS:
      All persons to whom home visits were made during the study period. MAIN RESULTS:
      138 home visits were made to 47 patients who had a mean age of 73.2 years. Home
      visits accounted for 1.4% of patient encounters in the practice, required a mean
      of 7.1 miles of one-way travel and a mean of 48 minutes, including travel time,
      to complete, and generated $36 in income per visit. Most patients (27 of 47) were
      not permanently homebound. Reasons for patients' being homebound were grouped
      into six categories (acute illness, frail elderly, terminal illness, advanced
      chronic disease, neurologic problem, and miscellaneous reasons). The reasons for
      visits were grouped into four categories (acute self-limited illness,
      exacerbation of chronic disease, routine follow-up of chronic disease, and
      psychosocial problem). Physicians judged that 80% of home visits represented
      appropriate use of their services. In addition, 46% of home visits made an
      emergency room visit unnecessary, and 9% made a hospital admission unnecessary.
      At the time of 75% of home visits, physicians reported personal benefits of
      making the visit. CONCLUSIONS: Home visits have an important role in the care of
      ambulatory as well as permanently homebound patients. While physicians judged
      most home visits to be appropriate and personally beneficial, these visits
      required more time and generated less revenue than did office visits for
      comparable problems. Because home visits generated as well as prevented the use
      of medical services, their impact on the overall cost of medical care in this
      setting is unclear.

PMID- 1403208
TI  - Physician detection of drinking problems in patients attending a general medicine
      practice.
AB  - OBJECTIVE: To assess the patient and physician characteristics that influence
      physicians' detection of problem drinking in their medical patients. SETTING: The
      outpatient medical clinic at an urban university teaching hospital staffed by
      interns and residents. DESIGN: Cross-sectional study of a randomly chosen
      subsample of consecutive patients. MEASUREMENT: Univariate and multivariate
      analysis with calculated adjusted odds ratios of factors associated with
      physician detection of drinking problems. A problem was diagnosed according to
      the patient's results on the alcohol module of the Diagnostic Interview Schedule
      (DIS). RESULTS: Physicians detected 22% of 189 presumably inactive problems and
      49% of 92 current problems, i.e., those that have occurred within the preceding
      year. Multivariate correlates of detection of active problems included male
      patient gender, presence of gastrointestinal complications of excessive drinking,
      number of concurrent medical disorders, and previous medical record reference to
      alcohol (p less than 0.05). Physician gender and year of training were not
      associated with detection. CONCLUSION: Our physicians appear to rely on specific
      patient characteristics as well as the patient's medical record to detect
      drinking problems in their ambulatory patients. Their reliance upon these factors
      may hinder their detection of drinking problems in women patients and less
      seriously impaired individuals.

PMID- 1403210
TI  - The splendor of internal medicine: it begins with patient care.

PMID- 1403211
TI  - Ambulatory opiate detoxification and primary care: a role for the primary care
      physician.
AB  - To determine the feasibility of primary care-based ambulatory opiate
      detoxification (AOD) and an optimal regimen, the authors conducted a pilot study
      of AOD in a medical clinic comparing two regimens: clonidine and clonidine plus
      naltrexone. Sixty-two opiate addicts who had been referred for AOD had the
      following features: mean age was 34 years, 75% were male, 74% used cocaine, and
      64% shared needles. Initially, 40 patients selected clonidine, 22
      clonidine/naltrexone. The groups (clonidine and clonidine/naltrexone) were
      similar in baseline features, including: craving scores (44/100 vs. 42/100) and
      withdrawal scores (20/72 vs. 17/72). Overall, 61% (38/62) of initial AODs were
      successful, including 43% (17/40) of those using clonidine and 95% (21/22) of
      those using clonidine/naltrexone (p less than 0.0001). Of 45 patients who
      ultimately completed AOD, 78% (35/45) remained in treatment for at least one
      month.

PMID- 1403212
TI  - Computer-generated mailed reminders for influenza immunization: a clinical trial.
AB  - A randomized, single-blind, controlled trial was performed at a community health
      center to measure the impact of computer-generated reminders mailed to patients
      on the rate of influenza immunization. High-risk patients were randomized to one
      of three groups: 1) usual care, 2) one reminder letter, offering free influenza
      immunization without an appointment, or 3) two sequential reminder letters,
      offering the same. The reminders did not significantly affect rates of influenza
      immunization. Analysis of the combined groups indicates that an appointment with
      a primary care provider remains the most reliable method of immunizing high-risk
      patients at this health center.

PMID- 1403213
TI  - Curriculum development and evaluation in medical education.

PMID- 1403214
TI  - Oral antibiotic therapy for acute pyelonephritis: a methodologic review of the
      literature.

PMID- 1403215
TI  - Osteoporosis: clinical features, prevention, and treatment.

PMID- 1403216
TI  - Matters of life and death: conversations among patients, families, and their
      physicians.

PMID- 1403217
TI  - X-rays for sinusitis: a matter of which or when?

PMID- 1403218
TI  - Preventing neonatal kidnapping.

PMID- 1403219
TI  - Pulse oximetry.

PMID- 1403220
TI  - Caring for HIV-seropositive patients.

PMID- 1403221
TI  - Nursing assessment and responsibilities in monitoring the preterm pregnancy.
AB  - Evaluating women for pregnancy-related problems that may result in preterm birth
      frequently requires electronic fetal monitoring at early gestational ages.
      Caution is needed to interpret information correctly from the preterm fetal heart
      rate and uterine activity tracings. Interpreting fetal heart rate tracings from
      preterm fetuses requires knowledge of fetal physiologic development. Obtaining
      clear tracings of preterm uterine activity remains a challenge and heightens the
      importance of thorough nursing assessment, including inquiry about risk factors
      for pregnancy complications.

PMID- 1403222
TI  - Maternal blood donation for intrauterine transfusion.
AB  - Pregnancy affected by erythrocyte alloimmunization often requires intrauterine
      transfusion for fetal survival. Because blood donated by a random donor has been
      associated with an increased risk of disease transmission, maternal blood
      donation has been advocated as an alternative blood source for intrauterine
      transfusion. Collaboration between medical, nursing, laboratory, and nutrition
      personnel optimizes the safety and success of the procedure. This article
      describes the collaborative care of the woman participating in maternal blood
      donation for intrauterine transfusion.

PMID- 1403223
TI  - Thermal effects of hooding incubators.
AB  - OBJECTIVE: To determine the effect of covering infant incubators on incubator
      wall and air temperatures, as well as on infant temperatures. DESIGN: A within
      subject ABA design, in which blankets covering the incubators were removed for a
      30-minute period and then replaced. SETTING: A neonatal intensive-care unit.
      PARTICIPANTS: Eight medically stable infants (gestational age, 28-33 weeks; birth
      weight, 913-1,947 g; and postnatal age, 2-39 days). INTERVENTIONS: Incubator wall
      and air temperatures as well as infant temperatures were measured during three
      study conditions: incubators covered (30 minutes), uncovered (60 minutes), and re
      covered (30 minutes). MAIN OUTCOME MEASURES: Incubator air and wall temperature;
      infant temperature. RESULTS: All incubator walls decreased in temperature after
      being uncovered; the decrease ranged from 0.6-2.2 degrees C. CONCLUSION: Although
      infants maintained relatively stable body temperatures during the uncovered
      period, the energy cost to their thermoregulatory efforts is unknown.

PMID- 1403224
TI  - Effectiveness of a pregnancy smoking cessation program.
AB  - OBJECTIVE: To evaluate two nursing approaches to promoting smoking cessation
      during initial antenatal visits. DESIGN: Experimental, with assignment to
      interventions using a random, alternate-day strategy and blind assessment of
      smoking at baseline, 1 month postintervention, 36 weeks' gestation, and 6 weeks
      postpartum. SETTING/PARTICIPANTS: 224 daily smokers, fewer than 31 weeks
      gestation, during first prenatal visit, at a teaching hospital antenatal clinic.
      INTERVENTIONS: An evening class providing guidance on a self-help program for 2
      hours on a group basis or 20 minutes on an individual basis during the prenatal
      appointment. MAIN OUTCOME MEASURE: Smoking cessation, confirmed by urinary
      cotinine levels. RESULTS: All women assigned to the referral intervention
      received a referral, but none attended the classes. In contrast, 93% assigned to
      the immediate intervention received the intervention. The group receiving
      immediate intervention had two to three times higher rates of cessation at all
      follow-up periods, with significant differences at the 1-month follow-up. There
      were certain similarities between the groups. CONCLUSION: Cessation interventions
      should be administered during the first prenatal visit.

PMID- 1403225
TI  - Use of home apnea monitors.
AB  - OBJECTIVE: To examine the frequency of use of home apnea monitors, reasons for
      not using them, and factors associated with their use among families of infants
      for whom home monitoring had been prescribed. DESIGN: Cross-sectional study,
      including a telephone interview to collect demographic data and a mailed
      questionnaire to obtain data on monitor use. SETTING: The apnea clinics in two
      tertiary-care centers. PARTICIPANTS: Ninety-three families (representing an 80.9%
      response rate) with infants considered at increased risk of sudden infant death
      syndrome and requiring home monitors. Infants with tracheostomies or
      bronchopulmonary dysplasia and families with monitored twins, a mother known to
      be drug addicted, or no home telephone were excluded. RESULTS: Of concern were
      that 23.1% of mothers reported using the monitor 12 or fewer hours per day and
      that 10.8% believed their infants did not need a monitor. Of 11 variables
      examined, only color change in the infant was associated with frequency of
      monitor use. CONCLUSIONS: Clear, consistent communication with families regarding
      the use of apnea monitors is essential to improve compliance with proper
      monitoring techniques.

PMID- 1403226
TI  - Effects of age, parity, and adherence on pelvic muscle response to exercise.
AB  - OBJECTIVE: To examine factors that affect pelvic muscle response to 12 weeks of
      pelvic muscle exercise. DESIGN: Repeated measures design in which intravaginal
      pressures during pelvic muscle contractions were recorded at baseline and after
      four exercise levels. SETTING: College of Nursing research site in Gainesville,
      Florida. PARTICIPANTS: Eighty-five parous, community-dwelling women, aged 35-78
      years and without incontinence as a primary concern. INTERVENTIONS: A 12-week
      graded program of regular (three times per week, every other day) pelvic muscle
      exercise at home. MAIN OUTCOME MEASURES: The hypotheses were that younger age,
      lower parity, higher baseline intravaginal pressures, and adherence to the pelvic
      muscle exercise program each would result in significant improvement in maximum
      intravaginal pressures. RESULTS: The only factor showing significance in
      predicting a successful outcome was age (t = -2.29, df = 41, one-tail probability
      = .0136). CONCLUSIONS: Regular, graded exercise over several weeks is needed to
      build pelvic muscles, and some women who exercise do not improve. Although the
      reasons for not improving are unclear, age is a significant factor.

PMID- 1403228
TI  - Current focus on cardiovascular function with angiotensin converting enzyme
      inhibitors in hypertension.

PMID- 1403227
TI  - Professional and lay interrater reliability of urinary luteinizing hormone surges
      measured by OvuQuick test.
AB  - OBJECTIVE: To determine the reliability of women, unmotivated by fertility
      problems, to accurately assess and record the urinary luteinizing hormone surge
      indicated by color changes on OvuQuick test pads. DESIGN: A descriptive,
      correlational study testing the reliability and validity of an instrument.
      SETTING: The participants' homes. PARTICIPANTS: 114 college-educated, white
      women. INTERVENTIONS: An OvuQuick Test Kit and a Menstrual Cycle Diary were
      mailed to each participant. The monthly diary and test pads of the participants
      were reassessed by a master's-prepared nurse. MAIN OUTCOME MEASURES: Women
      without medical or health-care training are reliable in judging the color changes
      on the OvuQuick test pads and recording these results in a menstrual diary.
      RESULTS: Investigator and subject assessment and recording of luteinizing hormone
      surge results agreed 95% (284 of 300 instances) of the time. In addition, the
      validity of the luteinizing hormone surge for predicting ovulation was accurate
      in 93% (26 of 28 instances) of the cases. CONCLUSION: OvuQuick is a reliable and
      valid test for home evaluation of luteinizing hormone surge and prediction of
      ovulation.

PMID- 1403229
TI  - Dose optimization study of arterial changes associated with angiotensin
      converting enzyme inhibition in hypertension.
AB  - BACKGROUND: In treating hypertension the optimal dose of angiotensin converting
      enzyme (ACE) inhibitor is derived from dose-response curves that relate the
      quantity of drug taken to the resulting fall in blood pressure; the blood
      pressure fall reflects a decrease in vascular resistance and hence, a degree of
      arteriolar vasodilation. However, ACE inhibition dilates not only the small
      arteries but also the larger calibre arteries, which increases compliance. Given
      the differences in structure and function of large and small arteries, the
      optimal drug dose for a given vessel may differ according to the size and
      structure of the vessel. DOSE-RESPONSE EFFECTS IN CLINICAL STUDIES: Clinical
      studies indicate that in the brachial artery territory, larger doses are required
      to obtain arterial dilation than to produce a decrease in vascular resistance. In
      the aorta, an improvement in arterial compliance and distensibility is governed
      both by the fall in blood pressure and the drug dose. Finally, for the femoral
      artery, the degree of arterial dilation is influenced markedly only by the drug
      dose. APPLICATION TO TREATMENT: An understanding of the drug dose required to
      produce a given change in the hypertensive arterial system may have important
      implications for the control of blood pressure. For a given mean arterial
      pressure, systolic blood pressure is lower and diastolic blood pressure higher
      when aortic compliance is increased, a haemodynamic change commonly seen
      following ACE inhibition. Recent double-blind studies have shown that ACE
      inhibitors produced a more pronounced decrease in systolic than diastolic blood
      pressure. CONCLUSION: These findings indicate that the optimum doses required to
      improve the arterial wall in large arteries must be evaluated by long-term
      antihypertensive therapy.

PMID- 1403231
TI  - The dose-response relationship with angiotensin converting enzyme inhibitors:
      effects on blood pressure and biochemical parameters.
AB  - CURRENT USAGE: Plasma angiotensin converting enzyme (ACE) inhibition and dose
      response relationships during blood pressure reductions were compared for several
      marketed ACE inhibitor compounds. Both peak and trough responses are considered
      and contrasted. The presently recommended antihypertensive doses of enalapril,
      lisinopril, perindopril and ramipril appear to lie within the linear range of the
      antihypertensive dose-response relationship. For benazepril and captopril, the
      recommended doses may be in the flat, upper part of the relationship.
      RECOMMENDATIONS: The recommended doses for initiating antihypertensive therapy
      may still be excessive in patients at risk of heightened pharmacodynamic
      responses. Further studies are required to clarify the dose-response relationship
      for all of these compounds.

PMID- 1403230
TI  - Use of ultrasonic and microsphere techniques to evaluate regional aspects of
      vasodilator therapy in myocardial ischaemia, arterial hypertension and heart
      failure.
AB  - PURPOSE: To review regional aspects of vasodilator therapy in myocardial
      ischemia, arterial hypertension and heart failure. DATA IDENTIFICATION: Results
      were obtained from experiments (1) performed either in experimental animals or in
      human volunteers or patients; (2) using either ultrasonic or microsphere
      techniques; (3) on the effects of different drug classes, including angiotensin
      converting enzyme inhibitors, calcium antagonists, potassium channel openers and
      nitrates; and (4) on the arterial and arteriolar vasodilating effects of
      different drug classes. CONCLUSIONS: The regional vasodilator effects, both
      arteriolar and arterial, of the major classes of drugs used in the treatment of
      coronary insufficiency, arterial hypertension and cardiac failure appear to be
      heterogenous. This heterogeneity is seen with a given drug in different vascular
      beds; within a class of drugs in a single vascular region; and between the
      regional vasodilator profiles of different classes of drugs. From the clinical
      point of view, the consequences of this heterogeneous vasodilation may be either
      positive (increase in flow, favourable redistribution of flow) or negative (steal
      phenomenon, opening of shunts).

PMID- 1403232
TI  - Use of monitoring software to improve the measurement of carotid wall thickness
      by B-mode imaging.
AB  - METHODOLOGY: High-resolution B-mode imaging is a reliable, easily performed and
      non-invasive means of studying atherosclerosis in superficial blood vessels.
      Recently it has been used for in vivo studies on the thickness of the common
      carotid artery wall. It is very sensitive, although the results of practical
      investigations are highly dependent on both the operator and the direction and
      angle of ultrasound beams directed towards the vessel. PROTOCOL: We have assessed
      inter- and intra-observer reproducibility of the measurement of common carotid
      artery wall thickness in 13 subjects, using two procedures. The first was a
      standard echographical investigation. In the second procedure, the principal
      parameters recorded from the first investigation were used to reposition the beam
      with the same incident angle. RESULTS: Intra-observer variability (correlation
      coefficient, r = 0.61 for procedure 1 and r = 0.77 for procedure 2) and inter
      observer variation (r = 0.58 for procedure 1 and r = 0.71 for procedure 2) were
      reduced when the second investigation was assisted by reproducibility software.
      CONCLUSIONS: The proposed method is a reliable and reproducible way of assessing
      combined intimal and medial wall thickness in the common carotid artery. It may
      be possible to improve reproducibility using specific software to aid the
      operator. Since the intimal and medial thickness of the common carotid artery
      appears to be a sensitive marker of vascular risk, the proposed standardized
      method of measuring these parameter may allow early detection and assessment of
      changes.

PMID- 1403233
TI  - Arterial mechanics and wave reflection with antihypertensive therapy.
AB  - PURPOSE: To describe a logical therapy for hypertension, based on functional
      elements of structural changes. EFFECTS OF STRUCTURAL CHANGES: Structural changes
      to large blood vessels in hypertension include medial degenerative changes, which
      stiffen arteries and increase pulse wave velocity, and intimal atherosclerotic
      changes, which narrow arterial segments. The former cause early wave reflection
      with increased systolic pressure in central arteries and the left ventricle. The
      latter compromise blood flow to vital organs. LOGIC OF VASODILATOR THERAPY:
      Vasodilator drugs with arterial dilating properties are the most logical and
      effective therapy. These agents decrease wave reflection from peripheral sites
      and so reduce systolic pressure in the left ventricle and central arteries; this
      effect is achieved both by decreasing the stiffness of peripheral arteries and by
      a differential effect on arterial calibre at branching sites. Arterial
      vasodilators also tend to dilate stenoses and collateral vessels and thereby
      minimize vascular 'steal', whereas arterial vasodilators (such as dipyridamole,
      hydralazine, prazosin) have little or no significant effect on wave reflection,
      and so fail to reduce the ill-effects of early wave reflection on the left
      ventricle and central arteries. Furthermore, by dilating arterioles in normal
      tissue, arteriolar vasodilators can cause vascular 'steal' in the heart or brain.
      CONCLUSIONS: The most effective vasodilators are those with both arterial- and
      arteriolar-dilating properties. Differential effects of vasodilators on arteries
      and arterioles can explain some differing effects of antihypertensive agents in
      clinical trials, as well as differing clinical responses in individual patients.

PMID- 1403234
TI  - Arterial structure in hypertension and the effects of angiotensin converting
      enzyme inhibition.
AB  - BACKGROUND: In hypertension, structural changes in the cardiovascular system
      affect not only small arteries and the heart but also the large arteries,
      particularly in elderly people. It has been suggested that structural alterations
      to the small arteries are responsible for the elevation in mean arterial pressure
      seen in hypertension, as a result of increased vascular resistance. However, the
      amplitude of pressure oscillation (pulse pressure) is influenced by other
      haemodynamic mechanisms that involve large arteries including a decrease in
      compliance and an increase in wave reflection. EFFECTS OF STRUCTURAL ALTERATIONS
      TO LARGE ARTERIES ON BLOOD PRESSURE: Structural alterations to the large arteries
      may, in hypertensive subjects, be responsible for an increase in the amplitude of
      pressure oscillation, leading to a disproportionate increase in systolic over
      diastolic blood pressure because of arterial (not arteriolar) changes. These
      findings not only contribute to a better understanding of the relationship
      between vascular structure and blood pressure levels but also to a better
      interpretation of hypertensive complications, particularly those related to the
      heart and large vessels. APPLICATION TO TREATMENT: The reversal of structural
      arterial changes may become a goal in long-term antihypertensive treatment.
      Angiotensin converting enzyme (ACE) inhibitors in particular can reverse
      structural arterial changes, increase arterial compliance and produce a more
      pronounced decrease in systolic than in diastolic blood pressure.

PMID- 1403235
TI  - Hypertension and the microcirculation: a brief overview of experimental studies.
AB  - PURPOSE: To review experimental findings on the importance of the
      microcirculation in hypertension. RESULTS OF DATA ANALYSIS: A significant part of
      the increase in vascular resistance found in hypertension involves alterations in
      the arteriolar network. Changes in vascular reactivity and amplification of
      normal microvascular autoregulatory loops are among the mechanisms involved in
      these microvascular alterations. Depending on the organ and the type of
      hypertension, different types of changes have been observed, including (1)
      changes in resting arteriolar diameter and increased tone, either throughout the
      arteriolar network or localized to certain arteriolar segments; (2) temporary
      closure of a significant fraction of the terminal arteriolar bed; and (3)
      degenerative processes in terminal arterioles and capillaries inducing anatomical
      rarefaction of the microvessels. CONCLUSIONS: Microvascular changes are
      responsible for only a portion of the increased resistance but they are extremely
      important in the global understanding of the hypertensive process, as they are
      potentially responsible for tissue damage and may be related to the increased
      risk of organ failure in hypertension.

PMID- 1403236
TI  - Blood rheology in arterial hypertension.
AB  - DETERMINANTS OF BLOOD RHEOLOGY: Blood flow depends on driving pressure and a
      resistance factor, the latter being related to geometrical hindrance and to the
      intrinsic viscosity of the blood. Since whole blood is non-Newtonian in nature,
      blood viscosity is strongly dependent on shear conditions. Low-shear areas occur
      in cardiovascular disease, and therefore the interaction between blood viscosity
      and flow conditions may affect vascular disorders. Increased shear stress
      secondary to increased viscosity may produce endothelial activation and release
      of endothelium-derived relaxing factors, leading to flow-dependent vasodilation.
      All the determinants of blood rheology, including plasma protein and erythrocyte
      factors may be altered in patients with arterial hypertension. BLOOD RHEOLOGY IN
      HYPERTENSION: A hyperviscosity state is created which is associated with an
      unfavourable prognosis, since it is correlated with blood pressure levels and the
      severity and complications of the disease including left ventricular hypertrophy.
      The mechanisms of haemorheological abnormalities in hypertension are still
      unclear. It is not known whether blood rheology is an independent variable in
      patients with hypertension or whether it is a covariable with other established
      indices of heterogeneity. However, many aetiopathological changes identified in
      hypertensive disease may contribute to the observed changes in blood rheology.
      Haemorheological changes in hypertension, through complex interactions with
      platelet activation and endothelial function, may contribute to the development
      of thrombosis and atherosclerosis. Moreover, in acute and chronic ischaemia and
      other conditions where compensatory mechanisms such as collateral formation and
      vasodilation are limited, rheological factors may become important determinants
      of blood flow and tissue oxygenation. TREATMENT EFFECTS: Many antihypertensive
      agents have direct or indirect potential effects on haemorheological variables.
      However, to date, most studies that have investigated the effects of therapy on
      rheological variables have not been performed in clinically relevant situations.
      Controlled studies that monitor both the acute and longterm effects of
      antihypertensive drugs on relevant haemorheological variables are required to
      show whether specific therapeutic approaches can correct abnormalities in blood
      rheology.

PMID- 1403237
TI  - Antihypertensive therapy in renal disease and transplantation.
AB  - HYPERTENSION AND RENAL DISEASE: In experimental models of renal disease not only
      protein intake and hyperlipidaemia but also hypertension may contribute to the
      progressive deterioration in renal function; in these models an imbalance in
      intrarenal haemodynamics appears to be a particularly important factor.
      ANTIHYPERTENSIVE THERAPY: A reduction in arterial pressure can alter the course
      of human chronic renal disease. However, it is not clear whether any one class of
      antihypertensive drug is superior to any other class in these patients.
      Angiotensin converting enzyme (ACE) inhibitors may prevent the progression from
      incipient to overt diabetic nephropathy and afford better protection than
      conventional treatment. In patients with non-diabetic renal disease there is no
      unequivocal evidence for a protective effect. In renal transplant recipients,
      mainly those taking cyclosporine, ACE inhibitors are equally effective compared
      to calcium antagonists in the control of hypertension, but their renal effects in
      transplant recipients without renal artery stenosis have not yet been assessed.

PMID- 1403239
TI  - Curvature and separation discrimination at texture boundaries.
AB  - Visual discrimination of contour curvature was investigated by using contours
      defined by the locus of points at which the phase of a square-wave grating was
      shifted by 180 degrees (a texture boundary). Curvature-increment thresholds were
      measured for contour curvatures from 0.31 to 10.65 deg-1, for grating spatial
      frequencies of 4.0 and 16.0 cycles per degree (cpd), and for gratings in either
      sine or cosine phase at the point of maximum curvature. Thresholds for these
      conditions were compared with curvature discrimination at black-white edges.
      Grating phase had no effect on performance at any curvature or grating frequency,
      but 16.0-cpd gratings produced a threshold elevation at all curvatures by an
      average factor of 2.4. Two-line separation discrimination was also measured for
      lines defined by texture boundaries. These data can be predicted by a model
      incorporating end-stopped complex cells of a type reported physiologically in
      primate area V2.

PMID- 1403238
TI  - Myocardial fibrosis and the concepts of cardioprotection and cardioreparation.
AB  - PURPOSE: To examine the inter-relationship between effector hormones of the renin
      angiotensin-aldosterone system and fibrosis, a determinant of abnormal myocardial
      stiffness, and to determine whether pharmacological interference with these
      hormones can prevent or regress this pathological structural remodeling. EFFECTS
      OF ANGIOTENSIN II AND ALDOSTERONE: Two morphological expressions of myocardial
      fibrosis are evident, a perivascular and interstitial fibrosis, not related to
      cardiac myocyte necrosis, and microscopic scarring that replaces lost myocytes.
      The former, a reactive fibrosis, is related to elevations in circulating
      mineralocorticoids (aldosterone or deoxycorticosterone) with increased dietary
      sodium, and not to arterial hypertension or ventricular loading. Scarring follows
      the cytotoxicity associated with elevated plasma angiotensin II levels and the
      increased K+ excretion that accompanies chronic mineralocorticoid excess. EFFECTS
      OF PHARMACOLOGICAL INTERFERENCE: Given the association of these hormones with
      fibrosis, the concept of cardioprotection was evaluated in various prevention
      trials. Reactive fibrosis was prevented in unilateral renal ischaemia by
      angiotensin converting enzyme (ACE) inhibition with captopril and in either
      primary or secondary hyperaldosteronism by antagonism of the aldosterone receptor
      with spironolactone. Scarring (and cell loss) was prevented in renal ischemia by
      captopril and by K(+)-sparing diuretics (spironolactone, amiloride) in primary
      hyperaldosteronism. In treatment trials, where reactive fibrosis was established,
      lisinopril promoted regression of the fibrosis and therefore was
      cardioprotective. CONCLUSIONS: Myocardial fibrosis is related to chronic
      mineralocorticoid excess (with increased dietary sodium), angiotensin II and
      increased K+ excretion. Cardioprotective and cardioreparative strategies that
      respectively prevent or regress the development of fibrous tissue have been
      demonstrated in experimental models and now merit clinical evaluation.

PMID- 1403240
TI  - Contrast dependence of the oscillatory motion threshold across the visual field.
AB  - Observer sensitivity to oscillatory step displacements of sine-wave gratings was
      investigated at various loci in the visual field (0-30 degrees) as a function of
      contrast. Detection thresholds at 10 Hz and high grating contrasts were
      approximately 11-15 arcsec in the fovea and 37-47 arcsec at 30 degrees
      eccentricity. At any given contrast, threshold displacement increases linearly
      with eccentricity. The data provide evidence against an interpretation based on
      cortical magnification, because the slope and the scale-free x intercept of the
      eccentricity function vary strongly with contrast. While foveal thresholds for
      high-contrast gratings are in the range of the hyperacuities, the oscillatory
      motion threshold falls off an order of magnitude more slowly than the traditional
      hyperacuities. Rather than conceiving of the oscillatory motion threshold as a
      spatial acuity limited by cortical magnification, we suggest an alternative
      approach that is based on a form of contrast discrimination. Oscillatory motion
      can be decomposed into the sum of a modulating counterphase grating and a static
      masking grating, both of which are in spatial quadrature (i.e., 90 degrees out of
      phase). At low grating contrast, oscillatory motion can be detected when the
      counterphase component exceeds a constant contrast value. Above a critical
      contrast value of the static component Cscrit, threshold rises as a power
      function of contrast with a slope near 1.0. The critical contrast value Cscrit
      increases linearly with eccentricity, indicating that oscillating gratings
      observed with the peripheral visual field are less easily masked compared with
      foveally fixated gratings.

PMID- 1403241
TI  - Achromatic form perception is based on luminance, not brightness.
AB  - Two figures were examined, one a subjective disk and the other a cup whose shape
      was revealed by shadows. The figures were presented in a single color on a
      background of a different color, and the observers adjusted the radiance of one
      color until, in the first case, the vividness of the subjective contour reached a
      minimum (minimum subjective contour) or, in the second case, the impression of
      depth that is due to shadows disappeared (shadow disappearance). The results for
      these two tasks followed the data for minimum flicker matches (made with the same
      stimuli) much more closely than those for direct brightness matching. We
      therefore claim that achromatic form perception in general and subjective contour
      and shadow perception in particular are based on the intensity dimension measured
      by flicker photometry, not on that measured by brightness matching. Finally, in
      agreement with these findings, bleaching of short-wavelength sensitive cones did
      not affect settings for subjective contours, shadows, or flicker photometry but
      did affect brightness matching.

PMID- 1403242
TI  - Interference of diffusive light waves.
AB  - We examine interference effects resulting from the superposition of photon
      density waves produced by coherently modulated light incident upon a turbid
      medium. Photon-diffusion theory is used to derive expressions for the ac
      magnitude and phase of the aggregate diffusive wave produced in full- and half
      space volumes by two sources. Using a frequency-domain spectrometer operating at
      410 MHz, we verify interference patterns predicted by the model in scattering
      samples having optical properties similar to those of skin tissue. Potential
      imaging applications of interfering diffusive waves are discussed in the context
      of the theoretical and experimental results.

PMID- 1403243
TI  - Intramedullary nailing of acute femoral shaft fractures without a fracture table:
      technique of using a femoral distractor.
AB  - Intramedullary nails were placed prospectively in 25 acute femoral shaft
      fractures in 25 patients without the use of a fracture table. A femoral
      distractor was used in 21 of the 25 patients to aid in obtaining and holding a
      reduction. Our goals were to determine if the technique was safe and effective
      for insertion of intramedullary nails in a wide spectrum of femoral fractures-
      with no increase in morbidity when compared to the use of the more familiar
      fracture table--and to determine the potential complications and pitfalls of
      using this technique. A retrospective evaluation of the most recent 25 patients
      with 27 femoral fractures that underwent intramedullary nailing on a fracture
      table was done to compare operative time, estimated blood loss, complications,
      and postoperative fracture alignment. In addition to the clinical evaluation,
      cadaveric dissections were undertaken to determine the exact location of the
      proximal distractor screw in relation to the contents of the femoral triangle.
      The femoral nerve was a minimum of 2.5 cm, and the femoral artery a minimum of
      3.0 cm from the proximal screw. In comparing the two studies, no significant
      difference was noted in the age of the patients, fracture types or locations,
      associated injuries, operative time, estimated blood loss, final fracture
      reduction, or nail position. No complications were encountered in the placement
      of the proximal femoral distraction screw. Although the distraction method is
      technically difficult because the reduction is obtained entirely during the
      procedure, there are certain situations when this technique could be employed
      with the benefit of decreasing intraoperative patient manipulation, thereby
      shortening operative time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403244
TI  - Fracture patterns and mechanisms in pedestrian motor-vehicle trauma: the
      ipsilateral dyad.
AB  - Pedestrians struck by motor vehicles have the highest mortality and morbidity
      rates of all motor-vehicle traumas. Fracture patterns and mechanisms were
      reviewed in a retrospective study of 115 consecutive patients. The most common
      fracture was tibia-fibula (39 patients), followed by pelvic (35 patients) and
      femur fractures (31 patients). A majority (90%) of long-bone fractures were the
      result of a direct-blow mechanism, and pelvic fractures were caused usually by
      lateral-compressive forces. Unstable pelvic and femur fractures both correlated
      with mortality (p less than 0.05), whereas tibia-fibula fractures (open or
      closed) did not. The triad of head, pelvis, and knee injuries traditionally
      associated with pedestrian motor-vehicle accident (MVA) victims was not found to
      occur with any statistical significance in this study group. Several
      characteristic fracture patterns were discovered: femur fractures associated with
      an accompanying pelvic fracture, and the ipsilateral dyad, an upper- and lower
      extremity fracture on the same side, were found to occur with statistical
      significance (p less than 0.05). A lower extremity fracture warrants particularly
      close attention to the examination of the corresponding upper extremity, and a
      femur fracture should alert the clinician to the possibility of pelvic injury.
      The ipsilateral dyad has not been described previously in the literature and
      should be appreciated by physicians evaluating and treating pedestrian MVA
      victims.

PMID- 1403246
TI  - Operative treatment of olecranon nonunion.
AB  - Records of five patients treated surgically for nonunion of the olecranon were
      reviewed. Four of the five fractures leading to nonunion were comminuted or
      oblique. Three nonunions occurred after tension band wiring, one nonunion
      occurred after open reduction internal fixation with a semitubular plate, and one
      nonunion occurred after treatment with a cast. The median interval from fracture
      to treatment of nonunion was 8 months. All nonunions were treated surgically.
      Four patients were treated with a tension band plate technique. All nonunions
      united at a median of 3 months. The median follow-up period was 36 months (range,
      12-48 months).

PMID- 1403245
TI  - Mason type II radial head fractures: operative versus nonoperative treatment.
AB  - The most appropriate treatment of Mason type II radial head fractures remains
      controversial. Recommended treatment has included closed reduction and
      immobilization, resection, or open reduction and internal fixation. The cases of
      29 Mason type II radial head fractures treated at Naval Hospital Oakland from
      1983 to 1989 were identified. Twenty-six or 90% were available for detailed
      follow-up. All cases underwent standardized elbow evaluations and results were
      compared using an elbow score based on a 100-point scale. The parameters
      evaluated were pain, motion, elbow and grip strength, and function in activities
      of daily living. In addition, injury and follow-up radiographs were analyzed.
      Mean follow-up was 18 months. There were 10 cases treated by open reduction and
      internal fixation and 16 cases treated by closed means. At final follow-up, the
      operatively treated group had a mean elbow score of 92 and 90% good/excellent
      results. The nonoperatively treated group had a mean elbow score of 77 and 44%
      good/excellent results. This difference was statistically significant (p less
      than 0.01). Radiographic analysis revealed a higher incidence of articular
      depression, displacement, and joint narrowing in the nonoperatively treated
      group. We conclude that displaced radial head fractures treated nonoperatively
      have a higher incidence of pain, functional limitations, loss of strength, and
      radiographic evidence of arthritis when compared to those treated by open
      reduction and internal fixation.

PMID- 1403247
TI  - A comparison of unicortical and bicortical end screw attachment of fracture
      fixation plates.
AB  - Plate fixation is considered by many clinicians to be the treatment of choice for
      displaced diaphyseal fractures of the forearm. One possible complication
      associated with plate fixation is refracture with the plate in situ or after
      plate removal. With the plate in situ, refracture typically occurs through the
      last screw hole near the end of the plate. Some clinicians have advocated the use
      of unicortical end screws to minimize the risk of such refractures. In this
      study, we performed a series of in vitro tests to compare the breaking strength
      of plated bone analogues that used either unicortical or bicortical end screws.
      The plated constructs that used unicortical end screws were significantly weaker
      in the two most important physiologic loading modes. Based on these results, we
      conclude that the use of unicortical end screws may result in a greater risk of
      refracture with the plate in situ.

PMID- 1403248
TI  - Skateboard and in-line skate fractures: a report of one summer's experience.
AB  - During a 5 month period, 26 skateboarding and 10 in-line skating fractures were
      seen at our institution. The radius was the most commonly injured bone in both
      groups. Forty-two percent of skateboard fractures required reduction and another
      16% required operative intervention. Epiphyseal fractures occurred in 42% of the
      skateboard riders who were skeletally immature. A greater proportion of high
      energy fracture patterns was recorded in contrast to earlier reports. Also, a
      trend towards injuries occurring on the street, as opposed to home, has been
      noted. Skateboard riders continue to shun protective gear and hitting a surface
      irregularity is the most common cause of fall. In-line skaters, on average, wear
      more protective gear and are more likely to continue riding after their injury.
      Routine protective gear and avoidance of street riding should be encouraged.
      Instructions stressing balance and control as opposed to showmanship are
      recommended. Caution is given to first time in-line skaters, as this appears to
      be an injury-prone period.

PMID- 1403249
TI  - Fibular osteosynthesis for delayed type II and type III femoral neck fractures in
      children.
AB  - Seventeen transcervical/basal femoral neck fractures in children were treated by
      free fibular graft and cancellous lag screw. Two cases were failures of a
      previous surgery, and 15 had been untreated for 3 weeks or more. Four cases had
      radiological evidence of avascular necrosis of the head and one of the neck
      preoperatively; five cases had neck resorption. At an average of 48.1 months
      postsurgery all fractures had united and there was only one new case of avascular
      necrosis. Four cases had coxa vara, and four cases had premature epiphyseal
      closure. There were 13 good, three fair, and one poor result(s) using Ratliff's
      criteria. We recommend this procedure in cases with delayed initial appearance or
      failed previous surgery. Complications of the procedure such as long screw/graft
      and fibular fracture are preventable. The incidence of coxa vara in cases with
      neck resorption may be reduced by adding subtrochanteric osteotomy to the
      procedure.

PMID- 1403250
TI  - The use of Ender nails in femoral shaft fractures: what are the remaining
      indications?
AB  - The use of Ender nails for the treatment of femoral shaft fractures has been
      described as technically easier and less time consuming than current
      intramedullary nailing techniques. We reviewed our results with unlocked Ender
      nails in 26 stable and 17 unstable fracture patterns an average of 3-4 years
      after injury. Because of continued instability, 42% of the stable and 76% of the
      unstable groups required adjunctive stabilization in the form of skeletal
      traction, a cast, or an external fixator. Additionally, nail migration and
      shortening and loss of motion at the knee were seen in 14 fractures in each
      group. Although two thirds of the patients with stable fracture patterns obtained
      good or excellent results, no outcome in the unstable group was rated excellent
      and only 19% were considered good. We therefore recommend that rigid locked
      intramedullary nails be used in femoral diaphyseal injuries. The use of Ender
      nails should be limited to stable fracture patterns and locked with screws or
      wires. They may be particularly useful for fractures in femora with small
      medullary canals (less than or equal to 8 mm), fractures below noncemented
      femoral prostheses, and fractures in young children requiring intramedullary
      stabilization without injuring the physeal plates.

PMID- 1403251
TI  - Alignment of supracondylar/intercondylar fractures of the femur after internal
      fixation by AO/ASIF technique.
AB  - Fifty-nine supracondylar-intercondylar fractures of the femur in 57 patients were
      evaluated after a mean follow-up of 5 years 7 months (range 2 years to 11 years 3
      months) after internal fixation using AO/ASIF technique. Axial alignment was
      compared with that of the uninjured side by orthoroentgenography in the upright
      position and by bilateral anteroposterior (AP) and lateral views of the femur.
      Identical values for varus/valgus were noted in 24%, for ante/recurvation in 72%,
      and for rotation in 61%; differences were within 5 degrees of varus/valgus in
      74%, of ante/recurvation in 78%, and of rotation in 83%. Alignment differences
      were more frequent in complicated and intercondylar fractures according to the AO
      classification of fractures. We conclude that restoration of the distal femoral
      angle is far more difficult than restoration of the sagittal plane and rotation,
      but a satisfactory functional result appears to be compatible with angulation
      differences of less than or equal to 5 degrees in any plane and that this
      difference appears to be within the reasonably achievable limits. 93% of the
      patients were satisfied; 64% of patients were pain-free, and 27% had slight
      intermittent pain (not interfering with daily activity); 67% of the patients had
      unlimited walking distance, and 78% of the patients were able to walk without
      aid. Excellent and good results according to the rating systems of Neer et al.,
      Pritchett, and Schatzker and Lambert were noted in 82, 39, and 26%, respectively.
      This discrepancy between alignment, pain, function, and results according to
      different rating systems underlines the need for future standardized, clearly
      defined reporting and classification of rating.

PMID- 1403252
TI  - Assessment of bone viability in patients with osteomyelitis: preliminary clinical
      experience with laser Doppler flowmetry.
AB  - The intraoperative determination of bone viability is of fundamental importance
      in the surgical management of osteomyelitis. Recurrent infection will result from
      inadequate debridement, whereas reconstructive problems will be magnified by
      overzealous resections. The purpose of this article is to report the use of laser
      Doppler flowmetry (LDF) as a surgical adjunct allowing quantitative determination
      of bone viability in patients with osteomyelitis. Twenty-five patients with
      osteomyelitis underwent surgical debridement using LDF to assist with the
      intraoperative identification of necrotic bone and have been observed for at
      least 6 months. The LDF probe is placed directly on the bone and the output
      signal is channeled into an oscilloscope that calculates and displays the mean
      value of the signal in millivolts (mV). All patients underwent radical surgical
      debridement, including hardware removal if present and resection of nonviable
      bone. Bone debridement was continued when possible until LDF measurements in
      excess of 100 mV were obtained. Information regarding bone vascularity obtained
      with the LDF had a direct influence on the extent of bone debridement in all
      cases. The patients have been observed for an average of 16 months. No
      complications were associated with the use of LDF. All readings were pulsatile.
      Five patients had recurrence of infection. The average LDF reading following
      debridement for patients with recurrent infection was 72 mV, compared to 107 mV
      for patients without recurrence (p less than or equal to 0.025). All fractures
      were healed, although some required supplemental surgical management, including
      bone grafting or external fixation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403253
TI  - Type II floating knee: ipsilateral femoral and tibial fractures with
      intraarticular extension into the knee joint.
AB  - Thirty-four patients with ipsilateral fractures of the femur and tibia with
      intraarticular extension into the knee of at least one fracture were reviewed at
      an average follow-up of 38 months. Joint involvement was present in 22 (65%)
      femoral fractures and 23 (68%) tibial fractures. In 11 (32%) patients, both
      fractures were intraarticular. In 71% of the patients, there were major
      associated injuries. Open fractures were common, occurring in 21 (62%)
      extremities. Associated vascular injuries were seen in seven (21%) cases. Ninety
      percent of the fractures were surgically stabilized. The average time to healing
      was 39 and 37.5 weeks for the femur and tibia, respectively. The average flexion
      of the knee was 96 degrees (5-140 degrees) with flexion contractures occurring in
      five (15%) knees. Results were graded according to criteria established by
      Karlstrom and Olerud. Only eight (24%) patients had good or excellent results.
      Complications were frequent, with deep infections occurring in 11 (32%)
      extremities, leading to above-knee amputations in three (9%) patients. This
      subgroup of floating knee injuries appears to be associated with a higher degree
      of systemic trauma, a higher percentage of open injuries, and a much graver
      prognosis.

PMID- 1403254
TI  - Indirect reduction and percutaneous screw fixation of displaced tibial plateau
      fractures.
AB  - Indirect reduction and percutaneous screw fixation were attempted in 20 displaced
      tibial plateau fractures in 20 patients. Closed, indirect reduction was
      successful in 18 fractures; two others, both Schatzker type II fractures,
      required open reduction. The 18 fractures were followed for an average of 16.2
      months (range, 12-24 months). Of the fractures successfully reduced with indirect
      techniques, 13 were reduced anatomically (72.2%), and five were considered
      nonanatomic (27.8%). Four of the five fractures with a nonanatomic reduction were
      type II fractures. Clinically, there were six excellent (33%), 10 good (56%), and
      two fair (11%) results. No fracture lost reduction; no patient developed an
      infection. Indirect techniques could effectively reduce only split fragments.
      Depressed fragments could not be reduced reliably with either ligamentotaxis or
      percutaneous elevation with a tamp. There was no correlation between radiographic
      reduction and clinical outcome. It did not matter whether two, three, or four
      screws were used to stabilize the fracture.

PMID- 1403255
TI  - Tibialis posterior muscle: the fifth compartment?
AB  - The posterior aspect of 51 embalmed cadaver legs in 50 cadavers was dissected to
      establish the prevalence of a separate compartment for the tibialis posterior
      muscle (TP). All dissections revealed the presence of a superficial and a deep
      posterior compartment. No distinct fascial septum separated the TP from the
      flexor digitorum longus (FDL) and flexor hallucis longus (FHL). We conclude that
      the TP does not commonly rest within its own osseofascial compartment and thus
      does not require isolated decompression for acute compartment syndrome of the
      leg. An incidental observation, frequently overlooked in the anatomy literature,
      was a supplemental tendon of origin of the FDL. In addition to the classically
      described tibial origin, several cadavers exhibited a proximal fibular tendon of
      origin for the FDL. One cadaver demonstrated the FDL to have an extensive fibular
      origin that completely covered the TP, forming a myotendinous fifth compartment.
      We feel that the variable fibular origin can explain the chronic exertional
      compartment syndrome of the TP described previously by Davey et al. and serves as
      a basis for a minor alteration in our fasciotomy technique.

PMID- 1403256
TI  - Postoperative radiographs as predictors of clinical outcome in unstable ankle
      fractures.
AB  - This study reviews a group of 80 consecutive displaced ankle fractures treated
      operatively and followed for an average of 3.2 years. Fractures included bone or
      combined bone and ligamentous injuries in which the initial talar displacement
      was greater than or equal to 2 mm. The immediate postoperative roentgenograms
      were examined for several features, which included widening of the syndesmosis,
      fibular length, talo-crural angle, talar tilt, presence and size of a posterior
      malleolar fracture, and an abnormality of the medial clear space. Patients were
      examined at follow-up per Cedell, and their clinical evaluations were correlated
      with the analysis of radiographic features and demographic data. Good to
      excellent results were seen in 80% of the cases. The radiographic factors most
      predictive of a poor outcome were abnormal medial clear space and the presence of
      a large (greater than 20%) posterior malleolar fracture (p less than 0.05).
      Fibular shortening, talar tilt, and syndesmotic widening suggested a poor result,
      but these findings were not statistically significant. Multiple (two or more)
      radiographic abnormalities correlated with a poor prognosis. Conversely, a
      perfect radiographic result did not guarantee an excellent clinical outcome.
      Older patients and those with a delay between injury and surgery greater than 7
      days tended to have a poorer result.

PMID- 1403257
TI  - Use of radial forearm flaps to treat complications of closed pilon fractures.
AB  - Between 1986 and 1990, five patients have been treated for full-thickness skin
      loss proximal to the level of the anterior joint line of the ankle following open
      reduction and internal fixation of closed C3 (ASIF) pilon fractures. The average
      delay from injury to the initial open reduction and internal fixation was 4.6
      days. Anteromedial and posterolateral incisions were used to expose the
      fractures, resulting in a bipedicle flap over the anterior aspect of the ankle
      joint at the time of the initial surgery. The minimum distance between these two
      incisions for these five patients was 6.0 to 9.0 cm (average of 7.4 cm). Free
      tissue transfers using the radial forearm flap were effective in providing
      durable but thin coverage for this difficult problem of soft-tissue coverage in
      an area requiring a thin flap with a long vascular pedicle. The risk for skin
      necrosis at the time of surgery may be minimized by spacing the incisions up to
      12.0 cm apart in addition to avoiding the period of maximal tissue ischemia
      occurring 3 to 6 days after the injury.

PMID- 1403258
TI  - Severe intracranial injury from a fall in the halo external fixator.
AB  - This is a report of a rheumatoid arthritis patient after atlantoaxial
      stabilization and halo external fixator immobilization who presented with
      intracranial injury after an accidental fall. Global aphasia and an impaired
      consciousness resulted from a cerebral hemorrhagic contusion below an impressed
      bone chip at the left posterior halo-pin site. Cranial penetration of a halo pin
      has been previously reported; however, brain injury associated with it has not.
      Since there is a considerable risk of falls in the elderly and in patients with
      myelopathic gait disturbances, this rare but potentially hazardous complication
      should be kept in mind during the halo vest fixation.

PMID- 1403259
TI  - Combined shear fractures of the trochlea and capitellum associated with anterior
      fracture-dislocation of the elbow.
AB  - This article presents two unusual cases of combined shear fractures of the
      trochlea and capitellum associated with anterior fracture-dislocation of the
      elbow. The mechanism of injury was thought to be a fall on the dorsum of a
      partially flexed forearm, in which the trochlea and capitellum are displaced by
      the fractured olecranon and the radial head.

PMID- 1403260
TI  - Transpedicular bone grafts misplaced into the spinal canal.
AB  - After open reduction of a burst fracture of L1, transpedicular bone grafting of
      the fractured vertebral body was performed. Bone grafts accidentally slipped into
      the spinal canal through the damaged medial wall of the pedicle. No adverse
      effects were noted clinically, but this case illustrates that transpedicular bone
      grafting is a potentially dangerous procedure. Computed tomography after 1 year
      showed complete resorption of the intraspinal bone grafts.

PMID- 1403261
TI  - Open reduction and internal fixation of an acetabular fracture during pregnancy.
AB  - Fractures of the pelvis and acetabulum are common injuries in a mechanized
      society and frequently occur in the younger age groups. Commonly associated
      injuries such as hemorrhage, urethral tears, gastrointestinal injuries, and major
      vessel damage are well reported and well known to orthopaedic surgeons. Another
      less frequently reported complication of pelvic fractures is the potential
      association with pregnancy and subsequent childbirth. This problem was first
      described by Malgaigne in 1857 in his classic article on double vertical
      fractures of the pelvis, in which he described a 34-year-old woman with a pelvic
      fracture who subsequently died during childbirth. A review of the literature
      reveals numerous articles addressing potential problems with parturition
      subsequent to a pelvic fracture and several articles dealing with pelvic
      fractures occurring during pregnancy. The current literature on pelvic fractures
      during pregnancy, however, recommends only nonoperative treatment and, to our
      knowledge, there have been no reports of operative fixation during pregnancy. The
      purpose of this article is to report a case of an acetabular fracture in a
      pregnant woman treated with open reduction and internal fixation, who went on to
      carry a full-term baby and have a normal delivery.

PMID- 1403262
TI  - Avascular necrosis of the femoral head--an unusual complication of an
      intertrochanteric fracture.
AB  - Avascular necrosis of the femoral head is an uncommon complication after
      intertrochanteric fracture. We report six patients with this unusual complication
      1-5 years after intertrochanteric fracture. The possible etiologies of this
      complication include a more proximal intertrochanteric fracture, a high-energy
      injury with fracture displacement resulting in vascular damage, and adverse
      influences of the operative procedures on the vascularity of the femoral head.

PMID- 1403263
TI  - Tibio-talo-calcaneal fusion with a free vascularized fibular graft in comminuted
      open fractures of the talus and the calcaneus.
AB  - An operation is described in which a free vascularized fibular graft with a
      peroneal cutaneous flap is used for tibio-talo-calcaneal fusion and simultaneous
      skin coverage in treatment of comminuted open fractures of the talus and the
      calcaneus involving large skin loss. Nine months postoperatively, the tibio-talo
      calcaneal arthrodesis was successful, with good coverage of the skin defect on
      the medial aspect of the sole. One year 7 months postoperatively, the patient is
      free of pain and able to walk with full weightbearing on the foot.

PMID- 1403264
TI  - In response to article by Dr. Helfet et al.

PMID- 1403266
TI  - In response to article by Drs. Hockenbury and Friermood.

PMID- 1403265
TI  - In response to article by Dr. Korovessis et al.

PMID- 1403267
TI  - In response to article by Dr. Doerr et al.

PMID- 1403268
TI  - Reestablishing our dental base.

PMID- 1403269
TI  - Critical analysis of mandibular reconstruction using AO reconstruction plates.
AB  - Forty-one cases (37 patients) of mandibular reconstruction using AO plates were
      reviewed. The patients' ages ranged from 27 to 83 years (mean, 52.3 +/- 18.1
      years) and their cases were followed for 6 to 42 months (mean, 12.7 +/- 8.3
      months). Cases were grouped by the location of reconstruction: anterior mandible
      crossing midline as group A (12 cases), body segment of the mandible as group B
      (16 cases), condyle and ramus of the mandible as group C (13 cases). The
      incidence of revision as a measure of outcome was calculated by actuarial methods
      accounting for loss to follow-up or death. Revision or plate removal occurred in
      22.2% (9 of 41 cases), with an incidence of 52.2% (6 of 12 cases) in group A,
      12.5% (2 of 16 cases) in group B, and 7.7% (1 of 13 cases) in group C. Combined
      use of an AO plate and bone graft had a revision rate of 33.3% (4 of 12 cases),
      whereas the reconstructions with only a plate had a revision rate of 17.2% (5 of
      29 cases). The difference between the immediate reconstructions (19.2%; 5 of 26
      cases) and delayed reconstructions (26.7%; 4 of 15 cases) was not significant,
      but delayed reconstruction of the anterior mandible resulted in the highest
      failure rate (57.1%; 4 of 7 cases). The revision incidence was significantly
      higher when the area had been radiated (33.3% of 24 radiated cases and 5.7% of
      nonradiated cases required revision). In particular, the radiated group A had a
      remarkably higher failure rate (63.2% of 10 cases).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1403270
TI  - Rigid reconstruction plates for immediate reconstruction following mandibular
      resection for malignant tumors.
AB  - Thirty-four primary alloplastic reconstructions of segmental mandibular defects
      caused by surgery for oral malignancy were performed during a 6-year period.
      Eighty-eight percent of the tumors were classified as stage III or IV. One third
      of the patients died during follow-up, nine with their primary reconstruction
      plate in place. During the follow-up, 12 patients required plate removal because
      of complications; four of them were treated with another plate. Nineteen of 21
      patients alive at the end of follow-up were free of disease. Ten had their
      primary plate in place, and four had had a secondary plate installed because of
      plate fracture or screw loosening. Three patients had their mandible permanently
      reconstructed with bone. The functional and esthetic results were considered
      excellent or fair in a majority of the cases. Because the 5-year survival rate
      for patients with advanced mandibular malignancies is 15% to 20%, extensive,
      definitive reconstructive procedures during primary surgery are usually not
      justified.

PMID- 1403271
TI  - Positional changes of the mandibular condyle assessed by three-dimensional
      computed tomography.
AB  - This investigation was designed to test the validity and reliability of three
      dimensional computed tomography (3-D CT) for quantification of positional changes
      of the condyle in a laboratory model. The model consisted of a mounted dried
      human skull and a mandibular condyle attached to a micromanipulator. Controlled
      changes in condylar position were made and the condyle/fossa was imaged.
      Positional changes were measured by triangulation methods based on specific 3-D
      CT landmarks. The data were analyzed using descriptive statistics, analyses of
      variance to evaluate the sources of variability, and linear contrasts to evaluate
      the differences between observed and expected values. The results indicated that
      selection of appropriate anatomic landmarks for assessment of movement influences
      technique accuracy. The data also indicate that 3-D CT is most accurate in
      detecting inferior condylar movements. Lateral and posterior movements were
      assessed with less accuracy than the inferior positional changes. The clinical
      significance of these differences has yet to be determined.

PMID- 1403272
TI  - Use of postauricular skin grafts for vestibular reconstruction.
AB  - The use of full-thickness postauricular skin grafts for vestibular reconstruction
      is described. The procedure offers the advantages of a concealed donor scar,
      minimal patient discomfort and morbidity, ease of procurement, and confinement of
      the operations to a single region. Its use in 17 patients (31 grafts) resulted in
      complete take in 90.3% of the grafts. Maintenance of vestibular depth in most
      patients was maintained at 1-year follow-up. The disadvantages of the procedure
      are the limited amount of skin available and the need to suture the graft to the
      recipient site.

PMID- 1403273
TI  - Evaluation of dexamethasone for reduction of postsurgical sequelae of third molar
      removal.
AB  - Sixty patients with bilaterally symmetrical impacted third molars participated in
      this double-blind, within-subject study to quantify the effects of 4 mg of
      dexamethasone on reducing postsurgical sequelae. Each patient's surgery was
      staged by mouth side and completed in two appointments 5 to 6 weeks apart. A
      preoperative dose of dexamethasone given intravenously was randomized to mouth
      side and surgical appointment; sterile water served as a control. Major areas
      assessed in this study were facial swelling, pain, and trismus. No difference in
      swelling and daily pain was noted. However, trismus and global pain were
      significantly affected by the steroid. Patients had a daily postsurgical increase
      in incisal opening of 4 to 6 mm over the control side during the examination
      period. Patients evaluated pain by choosing the least painful side. By a greater
      than 4:1 margin, patients chose the steroid side as the least painful side. No
      increase in the rate or type of complications was detected between control and
      steroid sides.

PMID- 1403274
TI  - Soft-tissue cephalometric norms in Chinese adults with esthetic facial profiles.
AB  - Using a double selection process comprised of professional and lay judges, the
      cephalometric tracings on a final sample of 48 Chinese adults with esthetically
      pleasing profiles were analyzed. The soft-tissue cephalometric norms and standard
      deviations of two widely accepted soft-tissue analyses, the Legan and Burstone
      analysis and the Holdaway analysis, were determined. In comparison with white
      norms, the Chinese nose was less prominent (P < .01), the nasolabial angle was
      less obtuse (P < .01), both the upper and lower lips were more protrusive (P <
      .05), the upper lip curvature was greater (P < .01), and the soft-tissue chin
      thickness was less (P < .05). This variance between racial types emphasizes the
      need to recognize that soft-tissue lateral cephalometric norms are specific for
      the racial group and cannot always be applied across different racial types.

PMID- 1403275
TI  - A model for osteoarthritis of the temporomandibular joint.
AB  - There is a need for a simple, reproducible animal model of advanced
      osteoarthritis of the temporomandibular joint (TMJ). In this study, gentle
      removal of the condylar articular layer in the sheep TMJ resulted in an eburnated
      condyle with peripheral osteophytes, thin or perforated discs, and temporal
      surface proliferation. This model can be used for both the study of
      osteoarthritis and the evaluation of therapeutic methods.

PMID- 1403276
TI  - Growth of the mandible following replacement of the mandibular condyle with the
      sternal end of the clavicle: an experimental investigation in Macaca mulatta.
AB  - This study was designed to investigate the long-term effects of transplanted
      clavicles to the temporomandibular joint (TMJ) in juvenile monkeys. Sixteen
      juvenile female monkeys (Macaca mulatta) were used in this experiment. Eight
      animals were used as controls and were allowed to grow undisturbed for an 18
      month period (group control). Eight animals were divided into two groups and
      underwent bilateral condylar excision via extraoral vertical ramus osteotomies.
      Four of these animals had their condylar segments removed and immediately
      replaced to serve as surgical controls (group condyle). The other four underwent
      condylar replacement with the sternal end of their clavicles (group SCJ).
      Standardized lateral cephalometric radiographs with the aid of tantalum bone
      markers were used to evaluate maxillary and mandibular growth. One-way analysis
      of variance (ANOVA) was used to determine the significance of differences between
      groups. All animals showed good mandibular function and a class I molar
      relationship following an 18-month evaluation period. Statistical analysis showed
      there was no significant difference in maxillary or mandibular growth between any
      of the three groups. The results of this investigation show that the sternal end
      of the clavicle may be a viable option in mandibular condylar transplant surgery.

PMID- 1403277
TI  - Management of the oral and maxillofacial surgery patient with end-stage renal
      disease.
AB  - Chronic renal failure (CRF) is the consequence of a multitude of diseases that
      cause permanent destruction of the nephron. Concurrent with renal failure are a
      host of changes affecting the homeostatic functioning of the individual. This
      report outlines the pathophysiology of CRF and highlights its effects on surgical
      manipulation of the oral and maxillofacial region in this patient population. In
      addition, some of the common physical findings and alterations in blood
      chemistries frequently observed in these patients are discussed.

PMID- 1403278
TI  - A large, painless mass in the submandibular space.

PMID- 1403279
TI  - Malignant schwannoma of the palate: a case report and review of the literature.

PMID- 1403280
TI  - Large odontogenic myxoma of the mandible treated by sagittal ramus osteotomy and
      peripheral ostectomy.

PMID- 1403281
TI  - Neurothekeoma of the oral cavity: case report and review of the literature.

PMID- 1403282
TI  - Recurrent arteriovenous malformation of the mandible: a case report.

PMID- 1403283
TI  - Postoperative variant of malignant hyperthermia: report of a case.

PMID- 1403284
TI  - Trochlear nerve palsy simulating an orbital blowout fracture.

PMID- 1403285
TI  - Treatment of an infected mandibular graft using tobramycin-impregnated
      methylmethacrylate beads: report of a case.

PMID- 1403286
TI  - Screw-wire osteosynthesis technique for intraoral open reduction of mandibular
      angle fractures.

PMID- 1403287
TI  - Chondrocytes in agarose culture synthesize a mechanically functional
      extracellular matrix.
AB  - The ability of chondrocytes from calf articular cartilage to synthesize and
      assemble a mechanically functional cartilage-like extracellular matrix was
      quantified in high cell density (approximately 10(7) cells/ml) agarose gel
      culture. The time evolution of chondrocyte proliferation, proteoglycan synthesis
      and loss to the media, and total deposition of glycosaminoglycan (GAG)-containing
      matrix within agarose gels was characterized during 10 weeks in culture. To
      assess whether the matrix deposited within the agarose gel was mechanically and
      electromechanically functional, we measured in parallel cultures the time
      evolution of dynamic mechanical stiffness and oscillatory streaming potential in
      uniaxial confined compression, and determined the intrinsic equilibrium modulus,
      hydraulic permeability, and electrokinetic coupling coefficient of the developing
      cultures. Biosynthetic rates were initially high, but by 1 month had fallen to a
      level similar to that found in the parent calf articular cartilage from which the
      cells were extracted. The majority of the newly synthesized proteoglycans
      remained in the gel. Histological sections showed matrix rich in proteoglycans
      and collagen fibrils developing around individual cells. The equilibrium modulus,
      dynamic stiffness, and oscillatory streaming potential rose to many times (>5x)
      their initial values at the start of the culture; the hydraulic permeability
      decreased to a fraction (approximately 1/10) that of the cell-laden porous
      agarose at the beginning of the culture. By day 35 of culture, DNA concentration
      (cell density), GAG concentration, stiffness, and streaming potential were all
      approximately 25% that of calf articular cartilage. The frequency dependence of
      the dynamic stiffness and potential was similar to that of calf articular
      cartilage. Together, these results suggested the formation of a mechanically
      functional matrix.

PMID- 1403288
TI  - Subchondral damage after acute transarticular loading: an in vitro model of joint
      injury.
AB  - Intact canine metacarpophalangeal and metatarsophalangeal joints were subjected
      to a variety of loads in vitro. Intraarticular fracture occurred in 19 joints
      loaded to an average force of 2.4 +/- 0.4 kN with a corresponding loading rate of
      88 +/- 23 kN/s. The remaining 29 joints were without gross evidence of fracture
      with an average load and loading rate of 1.7 +/- 0.9 kN and 64 +/- 32 kN/s,
      respectively. In the fractured specimens, damage to the zone of calcified
      cartilage and subchondral bone was much more extensive than was initially evident
      by gross inspection when assessed by scanning electron microscopy. Cracks with
      associated step-off displacement at the zone of calcified cartilage were found
      distant to the gross fractures. These findings were confirmed histologically. In
      addition, cracks localized to the zone of calcified cartilage were commonly
      identified histologically in specimens loaded in the range of 1.9-2.8 kN, but
      were not grossly fractured. The contact area determined with pressure-sensitive
      film increased with increasing load up to the point of fracture. The average
      pressure generated at the articular cartilage surface at the time of fracture in
      this model is > or = 40 MPa, and the fracture occurred at the contact site. Our
      findings suggest that failure in acute transarticular loading begins in the zone
      of calcified cartilage and subsequently involves the subchondral bone and
      overlying cartilage. This type of injury may contribute to the development of
      osteoarthritis after intraarticular fracture, or at high loads that do not result
      in gross fracture.

PMID- 1403289
TI  - Identification of integrin cell-substratum adhesion receptors on cultured rat
      bone cells.
AB  - The interactions of bone cells with their extracellular matrix is of major
      importance in bone development, repair, and disease. We examined the ability of
      rat calvarial bone cells to adhere to various matrix proteins and to define the
      role of integrin cell-substrate adhesion receptors in these interactions.
      Isolated newborn rat calvarial bone cells prelabeled with 3H-thymidine and plated
      on plastic wells that had been precoated with serial dilutions of various
      substrates showed typical dose-response adherence curves to fibronectin,
      fibrinogen, laminin, vitronectin, and collagen I and IV. Cell adherence to poly-D
      lysine, a nonspecific cell adherent, was high at all substrate concentrations >
      0.0001 micrograms/ml. A polyclonal anti-rat integrin antibody blocked cell
      adhesion to all substrates tested except poly-D-lysine. Isolated rat calvarial
      bone cells were surface labeled with 125I, extracted, and immunoprecipitated with
      polyclonal antibodies made against the rat integrin complex and peptides derived
      from the cytoplasmic domains of the alpha 2, alpha 3, and alpha 5 subunits.
      Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (nonreduced) identified four bands representing a mixture of integrins including
      the alpha 1 beta 1 laminin/collagen receptor, the alpha 5 beta 1 fibronectin
      receptor, and the alpha V beta 3 (or possibly alpha V beta 5) vitronectin
      receptor. These experiments show that bone cells adhere to a wide variety of
      extracellular matrix proteins via specific integrins. Increased knowledge about
      the regulation of these receptors and the mechanisms by which they transmit
      information to the cell will be important for a more complete understanding of
      bone physiology and pathophysiology.

PMID- 1403291
TI  - Cast immobilization and tibial diaphyseal blood flow: an initial study.
AB  - The effect of cast immobilization on blood flow to the tibial diaphysis was
      studied by the microsphere method, both before and after casting of one hindlimb
      of adult New Zealand White rabbits. Preliminary studies were undertaken to
      investigate the possibility of the reduction of tibial flow by the microspheres
      used for the control measurements of blood flow. There were no significant
      differences in the flows to the tibial diaphysis or skeletal muscle between the
      immobilized and control limbs after either 1 or 2 weeks. This similarity between
      control and experimental limbs indicates that immobilization had no major effect
      on tibial blood flow over and above the systemic effects of the procedure.

PMID- 1403290
TI  - Effect of short-term hypomagnesemia on the chemical and mechanical properties of
      rat bone.
AB  - Magnesium is known to have an essential role in determining the properties of
      bone, but the way in which Mg exerts its actions remains unclear. Although long
      term Mg deficiency is known to produce osteopenia, the effects of short-term Mg
      deficiency have not been established. To test the hypothesis that Mg deficiency
      results in an altered pattern of initial mineralization and concomitant altered
      bone properties, the radiographic, histologic, chemical, and mechanical
      properties of the bones of rats given a Mg-deficient diet were compared to those
      of rats pair-fed the same diet supplemented with Mg. Short-term Mg-deficiency in
      the diet of growing rats produced a significant decrease in both the trabecular
      bone volume and the mineral content of the newly formed metaphysis, a significant
      increase in the Ca:P ratio, and a slight, but significant increase in
      hydroxyapatite crystallite size and/or perfection in the metaphysis. Comparable,
      but not significant, trends were found in the diaphyses. Metaphyseal bone
      osteocalcin levels were reduced in the Mg-deficient rats and lipid was more
      easily extracted from their bones. No detectable alterations in radiographic
      microstructure were noted. Mechanically, a significant decrease in the maximum
      three-point bend strength of the femurs of Mg-deficient rats was observed. These
      data support the hypothesis that short-term Mg deficiency affects the pattern of
      bone mineral formation.

PMID- 1403292
TI  - Intraosseous infusion using the osteoport implant in the caprine tibia.
AB  - We evaluated the in vivo animal tolerance to intraosseous infusion via the
      Osteoport pediatric implant (model 2005PSO, Lifequest Medical, San Antonio, TX,
      U.S.A.) into the proximal tibia of immature goats and investigated the osseous
      effects of intermittent and sustained increases in intraosseous pressure (IOP).
      In group 1 (n = 3) autogenous whole blood was continuously infused (CI) for 5
      days at flow rates producing an IOP of 30-45 mm Hg. Group 2 animals (n = 3)
      underwent a 5-s high-pressure infusion (HPI) of lactated Ringer solution (LRS)
      producing an IOP of 90-125 mm Hg twice daily for 10 days. In group 3, the
      Osteoports were left in place 5 (n = 2) or 10 days (n = 2) and evaluated for
      patency at 72-h intervals. An IOP > 35 mm Hg produced clinical evidence of bone
      pain. Bone mineral density was significantly increased (p < 0.05) in all
      implanted tibias (mean 1.04 g/cm2; range 0.87-1.21 g/cm2) compared with controls
      (mean 0.67 g/cm2; range 0.65-0.71 g/cm2). A nonsignificant increase (+9% to +31%)
      in periosteal new bone formation occurred in all implanted tibias. In the
      continuously infused group, there was a significant increase (p < 0.05) in
      cancellous new bone formation (+483%), percentage eroded bone surface (+143%),
      and osteoclast covered bone surface (+255%) compared with controls. HPI of LRS
      did not produce significant bone changes. Seemingly, the Osteoport provided a
      ready means of intraosseous infusion and may be associated with less
      complications than current methods of continual vascular access. Bone changes
      correlated more with the duration than the magnitude of increased intraosseous
      pressures.

PMID- 1403293
TI  - Acute effect of traction, compression, and hip joint tamponade on blood flow of
      the femoral head: an experimental model.
AB  - Blood flow rates of the canine femoral head were experimentally determined during
      traction, compression, and hip joint tamponade using the hydrogen washout
      technique. In puppies, blood flow rate of the femoral head was significantly
      decreased with either traction or compression applied at one half body weight.
      Either maneuver, when combined with hip joint tamponade, reduced blood flow rate
      of the femoral head an average of more than 70% as compared with the initial
      control rate. In adult dogs, combinations of either traction or compression, at
      one-half body weight, with hip joint tamponade did not significantly decrease
      blood flow rate of the femoral head as compared with control values. Perfusion
      defect of blue silicone could be observed only in puppies around the hip during
      combinations of traction or compression with hip joint tamponade and involved the
      posterior superior capital branches of the medial circumflex artery and the
      arteries in the ligamentum teres. These experimental data may have important
      implications for the pathogenesis of iatrogenic avascular necrosis in the
      treatment of congenitally dislocated hip, Legg-Perthes disease, and avascular
      necrosis following nondisplaced femoral neck fracture.

PMID- 1403294
TI  - Partial pressures of oxygen and carbon dioxide in bone and their correlation with
      bone-blood flow: effect of decreased arterial supply and venous congestion on
      intraosseous oxygen and carbon dioxide in an animal model.
AB  - Pathological changes in bone have been related to a preceding impediment of the
      arterial or venous bone circulation and hypoxia. In this study, we analyzed the
      feasibility of mass spectrometry in measuring intraosseous oxygen and carbon
      dioxide. The partial pressures were also measured in intraosseous blood samples,
      and blood flow in bone was measured with the radioactive microspheres technique.
      The average partial pressure of oxygen in the lateral femoral condyle was 34 +/-
      1.6 mm Hg when measured in intraosseous blood samples and 36.3 +/- 2.3 mm Hg when
      measured with the on-line mass spectrometer, with significant correlation between
      the methods. The absolute value of the partial pressure of carbon dioxide
      measured in situ with mass spectrometry was correlated with the value in the
      withdrawn blood. There was no significant difference in partial pressures of
      oxygen and carbon dioxide between the two sides or between repetitive
      measurements. Arterial occlusion resulted in severe hypoxia, whereas more
      moderate changes followed venous occlusion.

PMID- 1403295
TI  - Failure of perfusion with oxygenated Krebs-Ringer solution to preserve the
      eccrine function of the vascular endothelium in bone.
AB  - An ex vivo canine tibia preparation was perfused at a constant rate with aerated
      (95% O2-5% CO2) Krebs-Ringer solution for 24 h. Bolus injections of
      norepinephrine (0.125-0.5 micrograms) were given and then acetylcholine (5 x 10(
      5) M) was used to stimulate endothelial production of smooth muscle relaxing
      factors. Following 1 h of perfusion the addition of acetylcholine resulted in
      significant attenuation of the response to norepinephrine (p < 0.001). After 4 h
      perfusion acetylcholine did not attenuate the norepinephrine response, but
      addition of L-arginine (the precursor of endothelial-derived relaxing factor)
      resulted in significant attenuation in the presence of acetylcholine (p < 0.005).
      At 6, 12, and 24 h the acetylcholine did not attenuate the norepinephrine
      response. It is concluded that normothermic, continuous perfusion with oxygenated
      Krebs-Ringer solution results in normal endothelial eccrine activity up to 1 h.
      Following this period there is substrate depletion but endothelial eccrine
      function can be demonstrated for up to 4 h. At 6 h this function cannot be
      demonstrated, suggesting degradation of the functional integrity of the
      endothelium.

PMID- 1403296
TI  - A theory of fatigue damage accumulation and repair in cortical bone.
AB  - An analysis is presented of the balance between the accumulation and repair of
      fatigue damage in osteonal bone. Fatigue damage is defined in terms of cracks
      seen histologically when precautions are taken to avoid preparation artifact. The
      rate of occurrence of such damage is assumed to be proportional to the product of
      applied peak-to-peak stress, raised to a power, and the loading frequency. The
      rate of damage repair is assumed to be proportional to the activation rate for
      osteonal remodeling, and to the mean cross-sectional area of the resulting
      osteons. An additional factor is introduced to account for the possibility that
      damage provokes nearby remodeling. The theory is used to compare data from
      previous experiments of two types: fatigue-to-failure, and studies in which
      histologically observable cracks are made more numerous by repetitive loading.
      The analysis shows that there is a measure of agreement between the results of
      the two kinds of experiments, but the current data are too limited, and the
      results are too dependent on the mode of loading, to adequately test the theory.
      However, the analysis provides a framework for designing experiments to more
      efficiently clarify the relationships between fatigue failure, cracks seen in
      histologic sections, and the rate at which such cracks are repaired by osteonal
      remodeling.

PMID- 1403297
TI  - Migration of porous coated acetabular prostheses fixed with screws: roentgen
      stereophotogrammetric analysis.
AB  - The fixation of screw-fixed, porous-coated acetabular prostheses was studied
      during 2 years in 21 patients (22 hips) using repeated roentgen
      stereophotogrammetric measurements. Migration of the center of the prostheses
      and/or tilting were recorded in five cups after 6 months. Two years after
      operation, migration was recorded in three, migration and rotation in six, and
      only rotation in three cups. Bone quality, prosthetic position, and immediate
      postoperative radiographic appearance of the prosthesis-bone interface did not
      correlate with the occurrence of migration. Narrow radiolucent zones had
      developed in half of the patients after 2 years and was associated with proximal
      migration. Micromovements of screw-fixed, press-fit cups seem to start later
      compared with previously presented results from cemented acetabular prosthesis.

PMID- 1403298
TI  - Determination of bone mineral density by dual x-ray absorptiometry in patients
      with uncemented total hip arthroplasty.
AB  - Bone remodeling is an expected sequela with total hip arthroplasty (THA).
      Although there are several methods of estimating bone response in THA patients
      from radiographs, there are no accurate and generally accepted methods for
      quantitative determinations in vivo. In this study, we describe an application of
      dual x-ray absorptiometry (DXA) for measuring bone mineral content and bone
      mineral density in the proximal femur following THA. DXA is a noninvasive
      technique with minimal radiation exposure (< 5 mrem). Various aspects of
      measurement error (accuracy and reliability) of this application of DXA were
      determined in a series of studies reported here. Accuracy error (how similar are
      the measured and actual values) was < 1% determined in bone phantoms of four
      densities. Precision error (how reproducible are the measurements) was also < 1%
      at all four densities in the phantoms and was only slightly elevated (0.9-1.5%)
      in repeated measurements of implanted cadaver femora. Precision error in vivo,
      determined both from multiple replicates on five patients and from duplicate
      scans on 30 patients, was further elevated but remained < 5%. Contributions to
      precision error, rotation of the leg, and interoperator variability were
      assessed; none was found to elevate precision error appreciably. We suggest that
      DXA is a feasible method for quantifying bone response following THA, and will
      allow discrimination of small changes (> 5%) not previously measurable.

PMID- 1403299
TI  - Effects of material properties of femoral hip components on bone remodeling.
AB  - Bone loss around femoral hip stems is one of the problems threatening the long
      term fixation of uncemented stems. Many believe that this phenomenon is caused by
      reduced stresses in the bone (stress shielding). In the present study the
      mechanical consequences of different femoral stem materials were investigated
      using adaptive bone remodeling theory in combination with the finite element
      method. Bone-remodeling in the femur around the implant and interface stresses
      between bone and implant were investigated for fully bonded femoral stems.
      Cemented stems (cobalt-chrome or titanium alloy) caused less bone resorption and
      lower interface stresses than uncemented stems made from the same materials. The
      range of the bone resorption predicted in the simulation models was from 23% in
      the proximal medial cortex surrounding the cemented titanium alloy stem to 76% in
      the proximal medial cortex around the uncemented cobalt-chrome stem. Very little
      bone resorption was predicted around a flexible, uncemented "iso-elastic" stem,
      but the proximal interface stresses increased drastically relative to the stiffer
      uncemented stems composed of cobalt-chrome or titanium alloy. However, the
      proximal interface stress peak was reduced and shifted during the adaptive
      remodeling process. The latter was found particularly in the stiffer uncemented
      cobalt-chrome-molybdenum implant and less for the flexible iso-elastic implant.

PMID- 1403300
TI  - Ligament tension pattern in the flexed knee in combined passive anterior
      translation and axial rotation.
AB  - Twenty-two fresh-frozen specimens were used to measure tensions generated in
      selected bands of the major ligaments of the flexed knee (40-90 degrees) when an
      axially prerotated tibia is subjected to passive anterior shear and when an
      anteriorly pretranslated tibia is subjected to passive axial torque. The tensions
      were measured using the buckle transducer attached to the anteromedial band of
      the anterior cruciate ligament [ACL (am)], the posterior fibers of the posterior
      cruciate ligament [PCL (pf)], the long fibers of the medial collateral ligament
      [MCL (lf)], and in the total lateral collateral ligament [LCL]. The knee
      specimens were subjected to the combined motions in a 6-df passive loading
      apparatus. The results indicated that the joint resistance to anterior
      translation increased markedly with internal prerotation and only marginally with
      external prerotation. This increase in joint resistance, however, was associated
      with a decrease in ACL function. It has been inferred that the posterior
      structures, capsular and meniscal, contribute significantly to joint resistance
      when the tibia is prerotated in either sense. For internal prerotation, the
      interference between the medial femoral condyle and the central tibial eminence
      was found to be an additional mechanism of resistance to anterior translation.
      Also, it has been found that although the ACL (am) tension increased with
      internal rotation in the normal case, it decreased with internal rotation in the
      presence of an anterior pretranslation. It is concluded that ACL response to
      combined joint motion cannot be ascertained by a simple summation of its
      responses to individual motions.

PMID- 1403301
TI  - Biomechanical effect of a two-segment anterior cruciate ligament graft with
      separate femoral attachments and differing levels of prescribed load sharing.
AB  - The objective of this study was to analyze the biomechanical effect of varying
      the level of prescribed load sharing between two segments of an anterior cruciate
      ligament (ACL) graft, and of separating the femoral attachments of these
      segments. Total anterior-posterior (AP) laxity was measured using an instrumented
      spatial linkage. Forces in graft segments were measured using buckle transducers.
      The two-segment graft was formed using the middle third of the patellar tendon
      with bone blocks and a synthetic augmentation device. Proximal fixation was
      obtained using a fixture which allowed changing the individual locations of the
      femoral attachments of the tendon and augmentation segments. Distal fixation was
      achieved using a force-setting device which allowed the loads in each segment to
      be set to prescribed levels. Total graft force, load sharing, and total AP laxity
      were recorded during the application of 100-N AP tibial loads at 0 degrees, 30
      degrees, 60 degrees, 90 degrees, and 110 degrees flexion, for various
      combinations of load sharing set at extension and locations of femoral attachment
      sites. The load sharing, total graft force, and AP laxity during AP loading at
      the five test flexion angles were not significantly affected by changing the
      prescribed level of load sharing set at extension for a given femoral attachment
      configuration. However, varying the separate hole locations of the graft segments
      for a given level of load sharing significantly affected load sharing, total
      graft force, and AP laxity. If the tendon graft was located posteriorly (on the
      medial surface of the lateral femoral condyle) and the augmentation segment
      proximally, the augmentation carried a greater portion of the total force in
      flexion. If the augmentation segment was changed to a more posterosuperior
      location and the tendon posteroinferior, the tendon carried a higher percentage
      of the total force in flexion. AP laxity in most reconstruction states was
      significantly greater than in the normal joint with an intact ACL. The nature of
      the load sharing between the graft segments under AP tibial load over the flexion
      range can be controlled by the appropriate choice of the segments' femoral
      attachment locations.

PMID- 1403302
TI  - The correlation between anterior-posterior translation and cross-sectional area
      of anterior cruciate ligament reconstructions.
AB  - Total anterior-posterior translation is commonly used to assess the integrity of
      the cruciate ligaments and the success of reconstructive surgery. The purpose of
      this study was to determine, after surgical reconstruction of the anterior
      cruciate ligament with a biological graft, if total anterior-posterior
      translation correlated with graft length, cross-sectional area, or mechanical
      properties. These factors were investigated by analyzing data from three previous
      studies. These studies involved replacement of the anterior cruciate ligament in
      cynomolgus monkeys and goats, with free and vascularized patellar tendon
      autografts and both patellar tendon and anterior cruciate ligament allografts.
      Data were available at time periods of 6 and 12 months after surgery. We found
      statistically significant inverse correlations between the amount of anterior
      posterior translation and cross-sectional area of a graft at the time of
      sacrifice. The Pearson correlation coefficients ranged from -0.966 (p < 0.002) to
      -0.830 (p < 0.05). We hypothesize that these correlations result from the
      following mechanism: the increased anterior translation reflects a slack graft; a
      slack graft is stress shielded by other structures about the knee; the reduced in
      vivo stresses on the graft modulate cellular metabolism in a way that over time
      produces a small cross-sectional area.

PMID- 1403303
TI  - Histological and biochemical analysis of the fibrous tissue induced by
      implantation of synthetic ligament (Dacron): an experimental study in a rat
      model.
AB  - We conducted a comparative study to evaluate the quality and true nature of the
      fibrous tissue formed around synthetic grafts when used in ligament replacement.
      In one group of Lewis rats, a patellar ligament was replaced with a Dacron
      prosthesis; the comparison group received a tail tendon isograft. Two-, 4-, 8-,
      12-, and 24-week comparisons showed histological and biochemical changes in the
      Dacron group alone that were consistent with foreign-body reaction. Specifically,
      the Dacron group showed infiltration by large numbers of macrophages and foreign
      body, multinucleated giant cells. In addition, the capsule of fibrous tissue that
      developed around the Dacron ligaments was characterized by lower collagen
      solubility, a higher content of noncollagenous protein, and a higher proportion
      of type III collagen than that comprising the isografted tendons. The results of
      this study call into question the suitability of synthetics for ligament
      replacement.

PMID- 1403304
TI  - Rigid immobilization alters matrix organization in the injured rat medial
      collateral ligament.
AB  - The effects of mobilization on matrix reorganization and density after ligament
      injury were studied in rat medial collateral ligaments using scanning electron
      microscopy (SEM). Both medial collateral ligaments of 14 Sprague-Dawley rats were
      sharply incised transversely at their midpoint. A 1.14-mm threaded Kirschner wire
      was driven through the tibia and into the femur of the right leg (through the
      knee) to immobilize that knee at 90 degrees of flexion. Four additional rats were
      used as controls. The right medial collateral ligament of the control rats was
      exposed in the same manner as the experimental rats and the wound closed without
      damaging the ligament. Rats were sacrificed on the 7th and 14th days postinjury
      and the ligaments evaluated by SEM. The electron micrographs from this study
      demonstrated that early on, the tissue at the injury site is disorganized on a
      gross scale with large bundles of poorly organized matrix. Large "defects" were
      present between bundles in the substance of the ligament and appeared as holes in
      the ligament around the injury site. As healing progressed, the matrix in the
      mobilized specimens appeared to bridge the injury site more rapidly and
      completely with fewer "defects" and thus higher density than the immobilized
      specimens.

PMID- 1403305
TI  - Strains and forces in selected carpal ligaments during in vitro flexion and
      deviation movements of the hand.
AB  - The forces induced in tiny wrist joint ligaments must be estimated in order to
      understand their role in the mechanism of the joint. We estimated forces in a
      number of selected ligaments in seven human wrist joint specimens, using a
      noninvasive method. The method is based on the rationale that the force generated
      in a ligament depends on its change of length with the joint under load. In vitro
      length changes of the ligaments were determined during flexion and deviation
      movements of the hand, using a roentgenstereophotogrammetric analysis technique.
      Subsequently, bone-ligament-bone (BLB) preparations were dissected from the
      specimens. From these BLB preparations the zero-force length and the force
      elongation relationship were determined in a material testing machine. The forces
      generated in the ligaments during flexion and deviation were calculated by
      combining results on the in vitro ligament length changes, the zero-force length,
      and the force-elongation relationship. Large interspecimen variations of the
      force patterns were found. Due to this variability, it is not possible to obtain
      quantitative models for the kinetic behavior of the ligaments. However,
      qualitative trends could be distilled from the strain and force patterns. It is
      clear that for most ligaments, the zero-force lengths were not equal to the
      lengths they possessed in the neutral position of the hand. Furthermore, it could
      be shown which motions of the hand would most likely strain a particular
      ligament. It could be shown that the variations in the force patterns originate
      mainly from variations in the zero-force lengths, and from variations in the
      force-strain relationship between specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403306
TI  - In vitro hyperextension injuries in the human cadaveric cervical spine.
AB  - To investigate the relationship between the type of hyperextension injuries and
      the conditions producing them, nine cervical specimens (occiput to T1) were
      loaded to failure in tension at a fixed extension angle of 30 degrees. Under
      these loading conditions, specimens failed at average tensile loads and extension
      moments of 499 +/- 148 (SD) N and 4.0 +/- 3.1 Nm, respectively. Failure occurred
      at an average tensile displacement of 18.8 +/- 7.7 mm. The anterior longitudinal
      ligament ruptured and the intervertebral disc failed in at least one level in all
      specimens. In four specimens, the disc failed at an additional level, leaving the
      anterior longitudinal ligament intact at that site. With one exception, all
      injuries occurred in the lower cervical spine (C5-C6 and C6-C7), the region most
      often injured in vivo. The location of the injuries was associated with the
      degree of degeneration of the facet joints and the discs. The discs of the lower
      cervical spine were significantly more degenerated than those at the C2-C3 level.
      In addition, the degree of disc degeneration in the noninjured discs was
      significantly less than in the injured discs. These data help quantify the
      threshold of injury and the patterns of tissue damage resulting from hypertension
      loading of the cervical spine.

PMID- 1403307
TI  - Forces and moments on the human leg in the frontal plane during static bipedal
      stance.
AB  - An experimental apparatus was assembled that permitted measurement of the
      vertical and lateral ground reaction forces as the hip is abducted, resulting in
      foot separations ranging from 0.25 to 71 cm, with the knee in 0 degree flexion.
      Twelve healthy volunteers (8 men and 4 women) were tested. The hip joint was
      located by means of center of rotation measurements on each subject's legs, and
      the location of the knee joint was determined using anatomical measurements. It
      was observed that the mediolateral force was nonzero and directed toward the body
      midline, even when the subject's feet were placed together. With the feet placed
      at shoulder width, the population mean mediolateral force was 3% of body weight.
      It was determined that simplifying assumptions based upon either "zero lateral
      force," or "zero hip moment," produced errors, when compared with our measured
      values, over various ranges of foot separation, with the zero hip moment
      assumption providing accuracy over a broader range. The inclination of the tibial
      plateau, with respect to the long axis of the tibia, that would produce minimal
      mediolateral shear at the knee is presented. Research and clinical applications
      of our results and techniques are discussed.

PMID- 1403308
TI  - Physiological cross-sectional area of human leg muscles based on magnetic
      resonance imaging.
AB  - Magnetic resonance imaging techniques were used to determine the physiological
      cross-sectional areas (PCSAs) of the major muscles or muscle groups of the lower
      leg. For 12 healthy subjects, the boundaries of each muscle or muscle group were
      digitized from images taken at 1-cm intervals along the length of the leg. Muscle
      volumes were calculated from the summation of each anatomical CSA (ACSA) and the
      distance between each section. Muscle length was determined as the distance
      between the most proximal and distal images in which the muscle was visible. The
      PCSA of each muscle was calculated as muscle volume times the cosine of the angle
      of fiber pinnation divided by fiber length, where published fiber length:muscle
      length ratios were used to estimate fiber lengths. The mean volumes of the major
      plantarflexors were 489, 245, and 140 cm3 for the soleus and medial (MG) and
      lateral (LG) heads of the gastrocnemius. The mean PCSA of the soleus was 230 cm2,
      about three and eight times larger than the MG (68 cm2) and LG (28 cm2),
      respectively. These PCSA values were eight (soleus), four (MG), and three (LG)
      times larger than their respective maximum ACSA. The major dorsiflexor, the
      tibialis anterior (TA), had a muscle volume of 143 cm2, a PCSA of 19 cm2, and an
      ACSA of 9 cm2. With the exception of the soleus, the mean fiber length of all
      subjects was closely related to muscle volume across muscles. The soleus fibers
      were unusually short relative to the muscle volume, thus potentiating its force
      potential.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403309
TI  - [High speed cinematographic analysis of subglottal mucosal vibration during
      experimentally induced phonation in excised larynges].
AB  - Twenty-seven excised canine larynges and two excised human larynges fixed on a
      wall of a specially constructed glass box, were blown on and the subglottal
      mucosal vibrations were photographed using high speed cinematography from the
      tracheal side. Each film was repeatedly projected at normal speed and analyzed
      frame by frame. Mucosal upheaval appeared between the anterior commissure and the
      vocal process. The mucosal wave or "traveling wave" started from the mucosal
      upheaval and propagated medially and upward. The mucosal upheaval vibrated with a
      small amplitude and with an earlier phase than any other portion of the vocal
      fold. Increase of air flow resulted in increased amplitude of the free edge
      excursion. The mucosal upheaval seemed to shift more laterally after the increase
      of air flow. But judging from the positional relations between the mucosal
      upheaval and markers, the origin of the mucosal upheaval was the same despite the
      increase of air flow. After the increase of vocal fold tension by cricothyroid
      approximation, the mucosal wave occurred within the limited area near the vocal
      edge. The mucosal upheaval was located more medially as compared to the original
      position. The mucosal upheaval appeared on what was actually the superior portion
      of the vocal fold. Direct electrical stimulation of the thyroarytenoid muscle
      (TA) bulged the lower surface of the vocal fold medially, and narrowed the
      subglottic area surrounded by bilateral mucosal upheavals during vibration. The
      mucosal upheaval seemed to shift more medially after stimulation of TA, but
      combined with the movements of the marker, the mucosal upheaval appeared on a
      more inferior portion of the vocal fold compared to its position before the
      stimulation. Thus, a more dynamic mucosal wave appeared in the vertical
      direction. Histological examination revealed that the mucosal upheaval arose on
      the lower surface of the vocal fold, slightly above the area where the muscular
      layer came close to the epithelial layer. After the cricothyroid approximation,
      the mucosal upheaval occurred in a more upward area where the lamina propria was
      thicker. In addition, after stimulation of the TA, the mucosal upheaval was
      located in the area where the muscular layer was thick under the epithelial
      layer.

PMID- 1403310
TI  - [Reflex control of laryngeal functions in the cat: the effect of vibratory
      stimuli of the laryngeal mucosa on the laryngeal reflex].
AB  - To investigate the effect of vibratory stimuli of the subglottic mucosa on the
      laryngeal reflex, experiments were performed on cats anesthetized with
      intraperitoneal injection of a mixture of urethane and chloralose. The external
      branch of the superior laryngeal nerve was cut, while the internal branch of the
      superior laryngeal nerve (ISLN) was mounted on stimulating electrodes.
      Electromyograms (EMG) were recorded from the contralateral thyreoarytenoid (TA),
      posterior cricoarytenoid (PCA), lateral cricoarytenoid (LCA), and cricothyreoid
      (CT) muscles. When the ISLN was electrically stimulated, the laryngeal reflex was
      induced. Short latency (early) and long latency (late) responses were observed in
      TA, PCA, LCA, and CT. Then, vibratory stimuli were applied to the surface of the
      subglottic mucosa. Vibratory frequencies used in this study were varied stepwise
      from 100 Hz to 400 Hz, with the amplitude adjusted at 20 microns. Vibratory
      stimuli had no effect on early responses but did, however, exert a facilitatory
      effect on late responses of TA and LCA in the transitional phase from inspiration
      to expiration and on late responses of PCA in the inspiratory phase. After
      denervation of ISLN, the vibratory effect on late responses disappeared
      completely. No significant vibratory effect was observed on CT in any respiratory
      phase. These results suggest that vibratory stimuli applied to the surface of the
      subglottic mucosa reflexively facilitate the laryngeal reflex and that ISLN
      afferents and respiratory drive modulate the laryngeal reflex.

PMID- 1403311
TI  - [Histological study of mucous membranes in the human nasal septum].
AB  - Histological changes in the mucous membrane of the human nasal septum in relation
      to deviation of the septum were investigated in this study. The mucous membranes
      of both the concave and convex sides of the deviated septum, were separately
      studied in 16 parts of the septum, which had been divided 5 ways in the anterior
      posterior direction and 4 ways from top to bottom in the vertical direction.
      Changes in the mucosa were also studied according to differences in age and
      gender. Specimens for this study were collected from 74 cadavers, including the
      autopsied cases of 44 males and 30 females, ranging in age from a prenatal stage
      of 22 weeks up to 84 years, from which cases with other nasal or paranasal
      diseases were excluded. The mucosa of the concave side consistently showed
      hypertrophic change in the height of the subepithelial mucosa, the area of mucous
      glands and the thickness of the muco-periosteum in each slice. This was assumed
      to be a finding influenced by prolonged septal deviation. Atrophy of the mucous
      epithelium and metaplasia into the squamous cell epithelium were frequently found
      in the middle portion and the population of goblet cells in the epithelium was
      increased predominantly in the slice from the posterior and bottom portions. The
      heights of the mucous epithelium and subepithelial mucosa were lower and the
      population of goblet cells decreased in relation to aging. However, atrophy of
      the mucous epithelium and increased thickness of the muco-periosteal layer
      predominated in the aged subjects. Sexual difference was revealed in findings of
      the height of the mucous epithelium, glandular area and thickness of the muco
      periosteum on the concave side of the septum. The height of the mucous epithelium
      was higher in females but the glandular area and thickness of the muco-periosteum
      was much more increased in males.

PMID- 1403312
TI  - [Difference between horizontal enlargement and vertical enlargement of the
      internal auditory meatus in acoustic neuroma].
AB  - Twenty-one patients with acoustic neuroma were investigated. The vertical
      diameter of the internal auditory meatus was measured by polytomography, the
      horizontal by target imaging CT. The ratio of the abnormal side to the normal
      side was calculated in each dimension. Two dimensional ratios were compared with
      each other in order to investigate the difference between horizontal and vertical
      enlargement of the internal auditory meatus. The results were as follows: 1)
      Horizontal enlargement of the internal auditory meatus was greater than that of
      the vertical one in 15 cases (75%). Vertical enlargement was greater in 6 cases
      but the difference between the two dimensions was not significant. 2) With
      horizontal enlargement, the posterior wall of the internal auditory meatus was
      more extended or destroyed than that of anterior wall. 3) With enlargement of the
      posterior wall, the bony eminence forming the inner side of the porus was
      predominantly extended or destroyed in every case.

PMID- 1403313
TI  - [Three-dimensional analysis of arteriography in human posterior circulation
      (preliminary report)].
AB  - In earlier articles it was suggested that there is a relation between vertigo and
      the posterior circulation. This study was designed to ascertain the course of the
      branches of the vertebral artery and the basilar artery, as well as the principal
      blood vessels of the vestibular nucleus by using radiographic three-dimensional
      observation. We studied 27 human brains (17 males, 10 females) fixed with the
      arterial embalming method at the Department of Anatomy of Kawasaki Medical
      School. The results were as follows: 1. Many variations in the course of the
      anterior inferior cerebellar artery and the posterior inferior cerebellar artery
      were observed, but the most frequent pattern, observed in 56% of our subjects,
      was the anterior inferior cerebellar arteries originating from the basilar artery
      and the posterior inferior cerebellar arteries from the vertebral artery. 2.
      Measurement of the inside diameter of both vertebral arteries showed the diameter
      of the left side to be thicker than that of the right side. 3. Perforating
      branches in the brain stem consisted of the pontine branches from the basilar
      artery and small branches from the anterior inferior cerebellar artery. Moreover,
      the transverse section showed a large number of them to originate from the
      ventral part of the brain stem.

PMID- 1403314
TI  - [Upper and lower airway diseases in children with persistent cough].
AB  - Persistent cough is a frequent and frustrating problem in the pediatric field.
      One hundred and seventy two children presenting with persistent cough for longer
      than 2 weeks were evaluated by both otolaryngologists and pediatricians. One
      hundred and twenty nine cases (75%) were found to have lower airway diseases, of
      which bronchial asthma, bronchitis and pneumonia, in that order, were the most
      common. One hundred and forty two cases (82%) had sinusitis, in 34 cases of which
      no causative diseases except sinusitis were found to be responsible for the
      persistent cough. Sinusitis was found in 90% of patients with pneumonia, 81% of
      those with bronchitis and 65% of those with poorly controlled asthma cases. These
      results revealed that sinusitis is an important causative factor for persistent
      cough in children. All the patients with pneumonia and bronchitis were cured by
      antibiotic administration for 2 weeks, whereas conservative treatment of
      sinusitis for as long as 6 months was less satisfactory resulting in only 60%
      cure, 18% improvement and 22% without improvement. In cases with sinusitis and
      lower airway diseases, continuous treatment for sinusitis is necessary even after
      treatment of the lower airway diseases has been completed.

PMID- 1403315
TI  - [Two cases of paranasal sinusitis with choanal polyp in children].
AB  - Patients with choanal polyp often suffer from maxillary sinusitis of the same
      side. Hence, Caldwell-Luc operation in addition to polypectomy has been
      recommended for the treatment of choanal polyp. Choanal polyp occurs more
      frequently in children with nasal polyp(s) than in adults with nasal polyp(s).
      For this reason, it is preferable to perform surgery so as to preserve the
      maxillary sinus as much as possible. The authors surgically treated two children
      with choanal polyp. A 12-year-old girl had a choanal polyp arising from the
      posterior portion of the middle turbinate and received an osteoplastic maxillary
      operation and functional endoscopic sinus surgery (FESS). The other, a 13-year
      old girl, with an antro-choanal polyp underwent FESS only. One year after
      surgery, both patients showed no recurrence of polyp and had recovered an aerated
      maxillary sinus cavity covered with normal mucous membrane. Based on the
      experiences of these two cases, FESS appears to be very helpful in treating
      children with choanal polyp and paranasal sinusitis.

PMID- 1403316
TI  - [Bacteriology of infectious disease in otorhinolaryngology (1). Bacteriological
      study of paranasal cyst].
AB  - The bacteriology of chronic sinusitis has been reported in several studies, but
      there have been few bacteriological studies on paranasal cyst. Also, details of
      the techniques of transportation and processing of clinical specimens have only
      rarely been described. Therefore, this study was undertaken with attention to the
      above, and to obtain information on appropriate antimicrobial therapy, we
      conducted a dilution antimicrobial susceptibility test of isolates. Fifteen
      patients with paranasal cyst participated in this study. Their lesions were
      frontal sinus (3), ethmoid sinus (2), sphenoid sinus (2) and maxillary sinus (8).
      We punctured the cyst using an 18-gauge needle attached to a syringe at the time
      of operation, and paranasal cyst effusions were promptly transported to the
      laboratory. The specimen was immediately inoculated under a set of aerobic and
      prereduced anaerobic plates, which were incubated in appropriate conditions. Most
      specimens were completely processed within one hour. Antimicrobial susceptibility
      testing of isolates was done with MIC panel by the Sceptor system. Positive
      results of bacterial cultures were found in 60% of all cases (all of the frontal
      sinus specimens and half of those with other lesions). A total of 38 bacteria,
      including 24 anaerobic and 14 aerobic species, were isolated from 9 paranasal
      cysts, yielding an average of 4.2 species per positive case (2.9 anaerobes and
      1.3 aerobes). Monomicrobial flora were found, anaerobes only in 2 cases and
      aerobes only in 2 others. Mixed flora were found in 5 cases in which both
      anaerobes and aerobes were isolated. The bacterial concentration in the maximal
      case was 4.9 x 10(4) CFU/ml. The organisms most frequently isolated were
      Propionibacterium spp. (7), Peptostreptococcus spp. (7), Staphylococcus spp. (7),
      Prevotella spp. (5) and Streptococcus spp. (4). On the basis of the results of
      antimicrobial susceptibility testing of isolates in vitro, the use of Cephems,
      Clavulanic acid/Amoxicillin, Norfloxacin and Chloramphenicol proved to be
      clinically effective.

PMID- 1403317
TI  - [Nuclear DNA pattern of thyroid tumor].
AB  - The nuclear DNA contents of 50 thyroid tumors were measured paraffin block
      samples and needle biopsies by using microscopic photometry, and the diagnostic
      value of this measurement was examined. Thyroid tumors included 17 papillary
      carcinomas, 15 follicular carcinomas and 18 benign tumors. The results confirmed
      the possibility of discriminating between benign and malignant tumors except in
      cases of follicular carcinoma with minimal invasion. This method seemed to be
      most valuable in the diagnosis of cases with class III FNA. A review was made of
      the relation between DNA content and prognostic factors, for example the degree
      of invasiveness of the thyroid tumor, intra-tracheal invasion, intra-thyroid
      metastasis and lymphatic metastasis. DNA content was increased only in cases with
      intra-tracheal invasion.

PMID- 1403318
TI  - [Ultrasonic study on tissues of parotid tumors--measurement of attenuation of
      ultrasound within tumors in vivo].
AB  - Pulse transmission technique has been used and developed in the Department of
      Otorhinolaryngology, Chiba University, in order to estimate attenuation of
      ultrasound within tumors of the parotid gland in vitro. A new apparatus to
      measure the attenuated ultrasound within the tissue was devised by using a pulse
      reflection method. After the measurement in vivo, the same examination was
      performed in a specimen of the removed tumor in vitro after surgery. Correlation
      between the characteristic of attenuation of ultrasound within the tissue in vivo
      and in vitro was investigated. The results in malignant parotid tumors were
      compared with ones in benign tumors of the parotid gland, too. The measurement of
      attenuation of ultrasound within a tumor in vivo was also compared with regard to
      the posterior echoes in ultrasound imaging, and then pathohistological study of
      the tumor was carried out in each case. The results of this study were summarized
      as follows: 1) Characteristics of ultrasound-attenuation within tumors in vivo
      were well correlated with ones in vitro. 2) Attenuation of ultrasound in
      malignant tumors tended to be stronger than that in benign ones. 3) Values of
      ultrasound-attenuation within tissues in vivo were also affected by the contents
      of collagen in them, which was reported in my previous study on tissues in vitro.
      4) Posterior echoes in ultrasound imagings were influenced by attenuations of
      ultrasound in tissues. However, the measurement of attenuation of ultrasound in
      tumors of the parotid gland is assumed to be helpful to promote the diagnostic
      value of sonographical examinations, and especially it would be useful for
      differential diagnosis of malignancies.

PMID- 1403319
TI  - [Exostosis of the external auditory canal and sensorineural hearing loss in
      professional divers].
AB  - Audiometric survey and endoscopic study of the external auditory canal were
      performed on a group of 31 professional divers, all of whom had experienced
      frequent exposure to dysbaric conditions. The results are as follows. 1) Over 40%
      had exostosis of the external auditory canal. There was no relationship between
      the incidence of the exostosis and the length of their occupational career as a
      diver. Many of the divers had hearing loss whether they had exostosis or not. 2)
      Over 70% had sensorineural hearing loss, taking into account hearing loss due to
      aging. Most had no experience of inner ear barotrauma on descent, causing sudden
      a shift in hearing threshold. Deafness was related to the length of their
      occupational career as a diver. In conclusion, we speculate that repetitive small
      changes in barometric pressure on the outer ear influences the pressure on the
      middle ear and further on that of the perilymph, finally damaging the inner ear
      auditory system.

PMID- 1403320
TI  - [A report of two cases of cervical necrotizing soft-tissue infection].
AB  - Two recent cases of cervical necrotizing soft-tissue infection are herein
      presented. Case 1. A 52-year-old man with uncontrolled diabetes was hospitalized
      because of an erythematous swelling of the left side of his neck and high grade
      fever. Fetid yellowish pus exuded from the left parotid area. The swelling
      extended from the left temporal area to the left supraclavicular fossa, with
      necrosis of the parotid gland, sternocleidomastoid, masseter and a portion of the
      strap muscles. Wound cultures revealed Staphylococcus aureus and alpha-hemolytic
      streptococcus. No anaerobic bacteria were detected. Treatment consisted of
      intravenous administration of antibiotics, control of diabetes with insulin, and
      debridement of the necrotic tissue, which left an epidermal defect in the
      initially swollen area. Transfer of a forearm free flap was done after the growth
      of healthy granulation tissue over the affected area. Case 2. A 55-year-old woman
      with rheumatoid arthritis was transferred to our hospital after tracheotomy
      performed in another hospital because of dyspnea due to severe crepitant swelling
      of her cheeks and submandibular areas bilaterally, and her left temporal area. A
      copious amount of fetid pus exuded from the incisions made in the left temporal
      area, left cheek, and right submandibular area. There were bilateral diffuse
      rales. Culturing the pus revealed alpha-hemolytic streptococci, while MRSA and
      Pseudomonas aeruginosa were detected from cultures of sputum. No anaerobic
      bacteria were found. After intravenous administration of antibiotics, infected
      wounds and pneumonia were ameliorated, and necrotic subcutaneous tissue and
      fascia were debrided. The patient was discharged with a residual depression in
      her left cheek and a scar on her left temporal area.

PMID- 1403321
TI  - [Clinical application of the smell identification test].
AB  - Clinical application of the standardized "scratch and sniff" olfactory test in
      Japanese is described. Over 300 subjects participated in three experiments. In
      experiment 1, 29 odorants used in the smell identification test were rated as to
      their experiences. The ratios of the experiences in each combination of odorants
      were compared. In experiment 2, the test was applied to normal subjects. Average
      test scores decreased as a function of age, with the greatest decline occurring
      between the sixth and tenth decades of life. In experiment 3, the test was shown
      to differentiate between subjects with olfactory disorders and normal controls.
      This self-administered test now makes it possible to rapidly and accurately
      assess general olfactory function in the laboratory, clinic, or through the mail
      without complex equipment or space consuming stores of chemicals.

PMID- 1403322
TI  - [Vocal function in Reinke's edema--degree of the lesion and indication of the
      operation].
AB  - Fifty three cases of Reinke's edema were classified into 3 groups according to
      Yonekawa's proposed classification. Of these cases, 14 were Type I, 22 were Type
      II and 17 were Type III. In each case, psychoacoustic evaluation using the
      "GRBAS" scale and phonatory function tests (fundamental frequency, air flow rate,
      sound pressure level and maximum phonation time) using Nagashima PS-77 phonatory
      function analyzer were performed. Psychoacoustically, the voice quality before
      surgery was estimated moderately impaired, in general, with high grade Roughness
      accompanied by Asthenisity and Strainedness. Cases with more severe lesions
      showed much worse psychoacoustic evaluation results and severely impaired
      phonatoy function, but they also showed greater improvement after surgery.
      Phonatory function improved significantly within a month and psychoacoustic
      evaluation improved significantly from 1 to 3 months after surgery, though
      neither returned to the normal range. In conclusion, we consider that surgical
      therapy is appropriate in Type II and III cases, with voice therapy and cessation
      of smoking also necessary for good recovery.

PMID- 1403323
TI  - [Progressing cases from low tone sudden deafness to Meniere's disease--cochlear
      impairment in the so-called pre-Meniere's disease period].
AB  - Among 80 patients with low tone sudden deafness (LTSD) who visited our department
      over the past 15 years, there were 6 cases (7.5%) who subsequently progressed to
      Meniere's disease. The clinical and audiological processes of the 6 patients were
      studied in detail and the following results were obtained. (1) In these 6
      patients, the time between onset of LTSD and the diagnosis of Meniere's disease
      ranged from 4 months at the shortest to 6 years and 8 months at the longest, 2
      years and 9 months on average. (2) Two pattern types were seen in the change from
      LTSD to Meniere's disease: changing within a short period of time after
      recurrence of an LTSD-like attack, and changing after more than one year without
      recurrent attack. (3) The monoattack-nonrecovered type of LTSD and the recurrent
      type of LTSD within three months after the onset (short-term prognosis)
      frequently progressed to Meniere's disease. (4) There were no close relationships
      between subjective symptoms and audiological features in the pre-Meniere's
      disease period (from the onset of LTSD to the recurrence of vertigo with cochlear
      symptoms). (5) The 6 patients showed various audiogram shapes at the time of
      progression to Meniere's disease; 3 cases with the slightly rising type, 1 with
      the high frequency-impaired type, and 2 with the moderate, gradual and flat type.
      (6) Of the 6 patients, 3 had good hearing during long term observation. At least
      2 patients seemed to have the mild type of Meniere's disease.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 1403324
TI  - [The effects of early manual instruction on the oral language development of two
      deaf children].
AB  - The speech and language training for deaf children at our clinic is performed
      using a multisensory method, which consists of reception and expression training
      for sign language and fingerspelling as well as auditory training, lip reading,
      and written language training (the Kanazawa Method). We have already reported
      that acquisition of written language is not dependent on oral language, and that
      written language is easier to learn than oral language for deaf children. In the
      present investigation, we analyzed the acquisition of comprehensible and
      expressive vocabulary in sign language and fingerspelling. The subjects were two
      children congenitally deaf at levels higher than 105dB. Recorded language samples
      by the age of 48 months were analyzed. Acquisition of sign language was found to
      be significantly easier than acquisition of oral language. The development of
      expressive noun words, function words, and Wh-question words in sign language at
      the early period was almost equivalent to that of hearing peers, and then the
      sign language appeared transfer to the oral language. These results suggest that
      early presentation of sign language with written and oral language is effective
      in the acquisition of communicative attitudes, function words and interrogative
      sentences which are most difficult for the hearing-impaired. It was shown that
      early presentation of sign language with written and oral language serves to
      promote acquisition of oral language.

PMID- 1403325
TI  - [A comparison of time resolution among auditory, tactile and promontory
      electrical stimulation--superiority of cochlear implants as human communication
      aids].
AB  - Our previous reports showed that second formant information, using a speech
      coding method, could be transmitted through an electrode on the promontory.
      However, second formant information can also be transmitted by tactile
      stimulation. Therefore, to find out whether electrical stimulation of the
      auditory nerve would be superior to tactile stimulation for our speech coding
      method, the time resolutions of the two modes of stimulation were compared. The
      results showed that the time resolution of electrical promontory stimulation was
      three times better than the time resolution of tactile stimulation of the finger.
      This indicates that electrical stimulation of the auditory nerve is much better
      for our speech coding method than tactile stimulation of the finger.

PMID- 1403326
TI  - [Intracochlear electrical stimulation of the auditory nerve in deaf kittens-
      brainstem response audiometric and histopathologic studies].
AB  - The effects of long-term electrical stimulation of the auditory nerve on the
      morphology of the cochlear nucleus were investigated in young pharmacologically
      deafened kittens. Comparing the amplitude of EABR with the soma area, there was a
      strong positive correlation between the amplitude of EABR and the soma area of
      neurons within the anterior ventral cochlear nucleus on the stimulated side.
      However, there was no correlation between the amplitude of EABR and the soma area
      of neurons within the unstimulated anterior ventral cochlear nucleus. In
      addition, there was no correlation between the amplitude of EABR and the survival
      rate of spiral ganglion cells. This showed that EABR may be affected not only by
      the survival rate of the spiral ganglion cell, but also by the development of the
      central auditory nervous system in kittens, which were deafened under the
      development of the central auditory nervous system.

PMID- 1403327
TI  - [Treatment of tinnitus with intravenous lidocaine].
AB  - Intravenous lidocaine was administered in 155 cases (196 ears) with tinnitus. The
      injection of lidocaine, at a dose of 60 mg in men and 40 mg in women was repeated
      five times. The intensity of tinnitus was evaluated along a scale ranging from 0
      to 10, indicating the level prior to injection. A scale ranging from 0 to 7 was
      estimated to be effective. After evaluation of the drug by using a double-blind
      test, indications for therapy were analyzed statistically according to clinical
      characteristics. The results obtained were as follows: 1) The effect was
      confirmed by using a double-blind test. 2) The effective rate was 60.2%. 3) Older
      cases, especially with presbyacusis, had the best indications for therapy. 4)
      From the clinical viewpoint of the characteristics of tinnitus, cases with
      hearing levels above 40dB or with dull onomatopoeic sounds were considered to
      have better indications for therapy. 5) None of the side effects experienced were
      severe, and all were transient.

PMID- 1403328
TI  - [Clinical study on the mechanism of motion sickness--clinical examination based
      on trigger factors].
AB  - This report deals with factors which trigger motion sickness. The author has
      focused on the clinical examinations applied to motion sickness cases.
      Relationships between clinical data and susceptibility to motion sickness were
      investigated. The following results were obtained: 1. CV R-R(coefficient of
      variation of R-R intervals on EGG)in the frequent motion sickness group showed
      higher values than in the occasional motion sickness group. This result suggests
      a hyperfunction of the vagus nerve. 2. In caloric testing with ENG, the motion
      sickness group showed lower values of duration and eye speed than the occasional
      motion sickness group. On the other hand, the frequent group showed higher values
      of laterality in eye speed than the occasional group. 3. With the visual
      suppression test, the frequent motion sickness group showed higher values than
      the occasional motion sickness group. On the other hand, there was a significant
      difference between the frequent motion sickness group and the occasional motion
      sickness group in terms of laterality of visual suppression values. 4. In testing
      fluctuation of CV R-R in response to optokinetic stimuli, the frequent motion
      sickness group showed elevation of CV R-R values after optokinetic load. On the
      other hand, the occasional motion sickness group showed depression of CV R-R
      values after the same load. 5. Among clinical examinations designed to diagnose
      susceptibility to motion sickness, CV R-R, the caloric test, the visual
      suppression test and OKP testing can produce sufficiently accurate results for
      clinical investigation.

PMID- 1403329
TI  - [The vertical component in a caloric nystagmus and the existence of a second
      phase of the nystagmus--the possibility of canal otolithic interaction in normal
      subjects].
AB  - To clarify the existence of the vertical component during a caloric nystagmus and
      the existence of a second phase of the nystagmus, 194 induced incidents of a
      caloric nystagmus in 29 normal subjects have been analyzed. Each nystagmus
      episode was recorded by using ENG and an infra-red video camera. The caloric
      stimuli were given by pouring 5 ml of water at 20 degrees C into the ear at an
      ear-up position. After irrigation, each subject then assumed a supine or a prone
      position, with the head bent 30 degrees forward in either position. All
      recordings contained vertical components that depended on the supine or prone
      head position and not on the side of the stimulated ear, i.e., an up-beating
      nystagmus resulted in the supine position and a down-beating nystagmus in the
      prone position. Further, the vertical component was far stronger in the prone
      position. In contrast, the horizontal component had larger velocities and was of
      longer duration in the supine position than in the prone position. When the first
      phase of the caloric nystagmus ended, the body position was changed 90 degrees,
      i.e., to a sitting position or a right-ear-down or left-ear-down position. All
      trials showed a horizontal component during the secondary phase when the head
      assumed the sitting position. As for the ear-down positions, only when the
      irrigated ear was moved upwards from the prone position during the secondary
      phase, an up-beating vertical nystagmus resulted in almost all the trials. These
      findings suggest that a caloric nystagmus may originate not only from the lateral
      semicircular canal but also from the vertical canals, and the second phase of a
      caloric nystagmus may be strongly influenced by the otolithic organs.

PMID- 1403330
TI  - [Immunohistochemical detection of glutathione S-transferase (GST) -pi in head and
      neck carcinoma and its changes by radiotherapy].
AB  - It is well known that the "placental form of glutathione S-transferase" (GST-pi)
      is present in high concentrations in most human carcinomas. However, its
      expression in head and neck carcinomas have not yet been reported. The author
      investigated the expression of GST-pi in the tissue of pharyngeal and laryngeal
      carcinomas by the immunohistochemical procedure, and the following results were
      obtained: 1) GST-pi was positive in 80% of laryngeal carcinomas (35 cases) and
      52.8% of pharyngeal carcinomas (36 cases). As a rule, well differentiated
      squamous cell carcinomas showed stronger expression of GST-pi than poorly
      differentiated squamous cell carcinomas. 2) Although normal epithelia of the
      pharynx and larynx showed negative GST-pi, it should be noticed that 54.6% of
      precancerous epithelia (11 cases) showed positive GST-pi. 3) Most patients
      treated with radiotherapy showed the diminution of GST-pi expression after the
      irradiation. However, co-relation between the strength of initial GST-pi
      expression and the effectiveness of radiotherapy was not observed (p < 0.01).

PMID- 1403332
TI  - A monoclonal antibody-based immunoassay for detecting tetrodotoxin in biological
      samples.
AB  - Spleen cells from mice hyperimmunized with a keyhole limpet hemocyanin
      tetrodotoxin-formaldehyde conjugate were fused with murine P3X63Ag8.653 myeloma
      cells. A single hybridoma clone was identified that secretes an IgG1,k monoclonal
      antibody (MAb), designated T20G10, against tetrodotoxin (TTX), with an estimated
      affinity of 1.2 x 10(8) L/M. Competitive inhibition enzyme immunoassays (CIEIAs)
      for detecting TTX were developed using this MAb. A direct CIEIA using alkaline
      phosphatase-labeled MAb detected TTX with sensitivities at IC50 and IC20 of 6-7
      ng/ml and 2-3 ng/ml, respectively. The accuracy of the direct CIEIA was
      comparable with the high-performance liquid chromatography (HPLC) and the mouse
      bioassay systems, but the direct CIEIA exhibited greater sensitivity. The direct
      CIEIA was also more cost effective, as it required less sample preparation, a
      shorter assay time, and reduced investment in equipment than either of the other
      assay systems.

PMID- 1403331
TI  - Sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for
      (anti-human T-cell leukemia virus type I) IgG in serum using a synthetic peptide,
      Cys-env gp46(188-224), as antigen.
AB  - A sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for
      (anti-human T-cell leukemia virus type I) IgG (anti-HTLV-I IgG) in serum using a
      synthetic peptide, Cys-env gp46(188-224) of HTLV-I, is described. Anti-HTLV-I IgG
      in test serum, which had been incubated with excess of inactive beta-D
      galactosidase to eliminate interference by anti-beta-D-galactosidase antibodies,
      was reacted simultaneously with 2,4-dinitrophenyl-bovine serum albumin-Cys-env
      gp46 (188-224) conjugate and Cys-env gp46 (188-224)-beta-D-galactosidase
      conjugate. The complex formed consisting of the three components was trapped onto
      polystyrene balls coated with affinity-purified (anti-2,4-dinitrophenyl group)
      IgG. After washing to eliminate nonspecific IgG in the test serum and excess of
      the beta-D-galactosidase conjugate, the complex was eluted from the polystyrene
      balls with epsilon N-2,4-dinitrophenyl-L-lysine and transferred to polystyrene
      balls coated with affinity-purified (anti-human IgG gamma-chain) IgG. beta-D
      Galactosidase activity bound to the (anti-human IgG gamma-chain) IgG-coated
      polystyrene balls was assayed by fluorometry. This assay was more sensitive and
      useful than the immune complex transfer enzyme immunoassay using Cys-Arg-env
      gp46(188-209) and other methods using HTLV-I as antigen.

PMID- 1403333
TI  - New developments in clinical laboratory molecular assays.
AB  - The new technological advances influencing the clinical laboratory are discussed
      with immediate and future areas of new clinical laboratory tests. The new
      technological advances include 1) monoclonal and designer antibodies, 2) solid
      phase and homogeneous automated immunochemical assays, 3) DNA/RNA nucleotide
      tests, 4) synthetic peptides, and 5) biosensors. The major factors which
      influence the need for future laboratory tests are 1) technology, 2) advances in
      therapeutic agents, 3) governmental regulations, and 4) health care economics.

PMID- 1403334
TI  - Clinical significance of soluble interleukin 2 receptor for monitoring the
      diseases associated with activated lymphocytes and viral infections.

PMID- 1403335
TI  - Laboratory diagnosis of parvovirus B19 infection.
AB  - The sensitivity and application of the polymerase chain reaction (PCR) for the
      diagnosis of parvovirus B19 (B19) infection was investigated by simultaneously
      assaying a collection of 279 consecutively received samples for presence of anti
      B19 IgM and IgG antibodies by Western blot and for B19 DNA by PCR and dot-blot
      hybridization (dot-blot); samples were sera from patients with suspected B19
      infection. PCR and dot-blot detected B19 DNA in 9% (16/179) and 1% (2/179),
      respectively of Ab-positive samples (IgM+/IgG-, IgM+IgG+, IgM-IgG+), and in 28%
      (15/54) and 2% (1/54), respectively, of IgM+ samples. PCR also detected B19 DNA
      in 2% (2/100) of IgM-/IgG- samples, both of which had normal total IgG and IgM
      levels. PCR is of unique value because it permits diagnosis of B19 infection even
      in the absence of specific acute phase (IgM) and in the presence or absence of
      convalescent-phase (IgG) Ab.

PMID- 1403336
TI  - Development of a rapid microparticle-enhanced nephelometric immunoassay for serum
      myoglobin in acute myocardial infarction.
AB  - A microparticle-enhanced nephelometric immunoassay was developed for myoglobin
      quantitation in human serum. It uses rabbit antimyoglobin serum and hydrophilic
      polyacrylic microparticles covalently coated with baboon myoglobin in a
      competitive immunoagglutination system. The level of microparticle agglutination
      is assessed with a specially designed nephelometer. This sensitive (45 ng/ml of
      myoglobin detected in serum) and accurate (coefficients of variation from 3.0% to
      8.2% in precision study and linear recovery of myoglobin in overloaded sera)
      immunoassay was evaluated with human sera from patients suffering from acute
      myocardial infarction. Myoglobin levels in patient's serum on admission appeared
      to be correlated with clinical and biological parameters assessed in emergency
      wards and later. This new, rapid, and easy microparticle-enhanced nephelometric
      immunoassay could thus be useful in emergency conditions for the early
      quantitation of serum myoglobin.

PMID- 1403337
TI  - Enzyme-linked immunosorbent assay to measure apolipoproteins AI and B secreted by
      a human hepatic carcinoma cell line (Hep G2).
AB  - We describe an enzyme-linked immunosorbent assay (ELISA) to measure
      apolipoproteins AI and B secreted by Hep G2 cells and in cell homogenates. These
      assays utilize commercially available polyclonal antibodies, affinity-purified to
      improve their specificity, thereby achieving a dramatic increase in the
      sensitivity of the assay. These affinity-purified antibodies were also more
      sensitive than a series of monoclonal antibodies tested. We achieved a
      sensitivity of 0.4 ng in the apo AI assay, and a sensitivity of 5 ng in the apo B
      assay. By these methods, we measured secretion rates by Hep G2 cells of 358 +/-
      41 ng/mg cell protein/hr for apo B and 137 +/- 8 ng/mg cell protein/hr for apo
      AI. These assays also allowed the measurement of intracellular apolipoproteins
      and thus can be used to facilitate investigations of human lipoprotein metabolism
      in cell culture systems.

PMID- 1403338
TI  - A simple ICP-MS procedure for the determination of total mercury in whole blood
      and urine.
AB  - A simple and sensitive procedure for total mercury in whole blood and urine using
      inductively coupled plasma-mass spectrometry (ICP-MS) is described. Specimens are
      prepared by precipitation-extraction with 50% v/v hydrochloric acid containing
      EDTA and cysteine, centrifuged, and filtered through fritended screening column;
      the filtrates are directly analyzed by ICP-MS. The method is linear between 2 and
      200 micrograms/L in the specimen with an absolute sensitivity of 0.2 microgram/L
      in the final supernatant. The assay variability at various concentrations
      (microgram/L) of mercury are as follows: intra-assay whole blood (n = 20)-4.6 +/-
      0.6 (c.v. 12.3%), 18.3 +/- 1.1 (c.v. 6.1%), 56.4 +/- 2.8 (c.v. 5.0%); inter-assay
      whole blood (n = 15)-5.7 +/- 1.0 (c.v. 16.8%), 19.7 +/- 2.7 (c.v. 13.5%), and
      50.1 +/- 6.9 (c.v. 13.7%); urine (n = 20)-9.3 +/- 1.2 (c.v. 12.9%), 29.6 +/- 2.2
      (c.v. 7.4%). Recovery of organic and inorganic mercury from blood samples ranges
      from 91.6% to 110.2%. The method is suitable for analysis of total mercury, both
      organic and inorganic, in whole blood and urine.

PMID- 1403339
TI  - Acid pH-induced changes in the immunoreactivity of specific antigen and antibody
      in circulating immune complexes from tuberculosis sera.
AB  - The effect of acid pH treatment of circulating immune complexes (CIC) derived
      from tuberculosis sera was studied on the relative titers of specific antibody
      (CIC Ab) and mycobacterial antigen (CIC Ag) in the complexes. While the specific
      antibody titers increased, the titers of CIC Ag declined as a result of acid pH
      treatment of CIC, both changes being highly significant statistically. Direct
      exposure of TB sera to pH 2.8 also resulted in significant enhancements in the
      titers of antibodies directed against Mycobacterium tuberculosis (M.tb.).
      Competition experiments indicated that the acid pH-treated antibodies retained
      their antigen specificity. TB sera treated with pH 2.8 for 30 min and then
      neutralized back to pH 7.4 retained the enhanced antibody reactivity even after 7
      days of storage at 4 degrees C. Our results indicate that acid pH treatment
      induces higher antigen binding ability in anti-M.tb. antibodies, present in free
      or complexed form in TB sera. These changes appear to be irreversible.
      Dissociation of CIC and analyzing the titers of released antibody and antigen
      components offered no advantage with respect to the immunodiagnosis of
      tuberculosis, as compared to the levels of undissociated CIC components or the
      serum antibody.

PMID- 1403340
TI  - Novel and ultrasensitive noncompetitive enzyme immunoassay (hetero-two-site
      complex transfer enzyme immunoassay) for alpha-human atrial natriuretic peptide.
AB  - A novel and ultrasensitive noncompetitive enzyme immunoassay (hetero-two-site
      complex transfer enzyme immunoassay) for alpha-human atrial natriuretic peptide
      (alpha-hANP) in plasma is described. alpha-hANP was biotinylated using N
      hydroxysuccinimidobiotin and trapped onto an anti-alpha-hANP [6-28] IgG-coated
      polystyrene ball. After washing, biotinylated alpha-hANP was eluted from the
      polystyrene ball with HCI and was reacted with 2,4-dinitrophenyl-fluorescein
      bovine serum albumin-disulfide-rabbit anti-alpha-hANP [6-28] IgG conjugate. The
      complex formed was trapped onto (anti-2,4-dinitrophenyl group) IgG-coated
      polystyrene balls and, after washing, reacted with avidin-beta-D-galactosidase
      conjugate. The polystyrene balls were washed, and the complex of the three
      components was eluted with epsilon N-2, 4-dinitrophenyl-L-lysine and transferred
      to anti-fluorescein IgG-coated polystyrene balls. After washing, the complex was
      released from the polystyrene balls by reduction with 2-mercaptoethylamine and
      transferred to (anti-rabbit IgG) IgG-coated polystyrene balls. beta-D
      Galactosidase activity bound to the last polystyrene balls was assayed by
      fluorometry. The detection limit of alpha-hANP [1-28] was 3 fg (1 amol)/tube.
      Interference by plasma proteins was eliminated by separation of peptides from
      proteins using a molecular sieve. The assay range of plasma alpha-hANP [1-28] was
      0.04-120 ng/L, and plasma levels of hANP in healthy subjects (11-56 ng/L) were
      measured without concentration.

PMID- 1403341
TI  - Comparison of serum amyloid A and C-reactive protein as indicators of lung
      inflammation in corticosteroid treated and non-corticosteroid treated cystic
      fibrosis patients.
AB  - Serum amyloid A (SAA) and C-reactive protein (CRP) levels were compared in 830
      serum samples from 155 cystic fibrosis (CF) patients. Correlation coefficients
      were calculated for all samples (r = 0.73), for samples from non-corticosteroid
      treated (CFNS) patients (n = 698, r = 0.80), and for samples from corticosteroid
      treated (CFS) patients (n = 132, r = 0.35). SAA was the more sensitive indicator
      of pulmonary inflammation when SAA and CRP were compared to pulmonary function
      tests of 49 hospitalized patients at admission and discharge. CRP levels were
      significantly (p less than .05) lower at admission in CFS patients than in CFNS
      patients, whereas SAA levels were not significantly different between the two
      groups. All nine CFS patients hospitalized had elevated SAA levels (average 22
      times above normal limits) at admission, while only six had elevated CRP levels
      (average 3.7 times above normal limits) at admission. In the 40 CFNS patients
      both SAA and CRP levels were significantly elevated at admission. In each case
      SAA and CRP levels declined as pulmonary functions improved with effective
      antimicrobial therapy. In three instances SAA levels increased during
      hospitalization while CRP levels did not. In each case, rising SAA levels
      indicated clinical deterioration associated with evolving resistance of P.
      aeruginosa which required a change in antibiotic therapy.

PMID- 1403343
TI  - Automated quantitative nephelometric latex immunoassay for determining ferritin
      in human serum.
AB  - We describe a rapid and sensitive latex nephelometric immunoassay for quantifying
      ferritin in human serum. This latex immunoassay procedure uses commercially
      available ready-for-use reagents [Tina-Quant (a) Ferritin, Boehringer Mannheim]
      that have a long shelf life. The assay consists of incubating the diluted serum
      sample (5-fold) for 12 min at room temperature with latex particles covalently
      coated with anti-ferritin antibodies, and then quantifying the change of light
      scatter produced. The assay is fully automated on the Behring nephelometer
      analyzer with a sampling rate of 150 samples/hour. The method has an analytical
      range of 3 to 260 micrograms/l. Maximal intra- and inter-assay CVs were 4.0 and
      6.2%, respectively. Analytical recoveries ranged from 91.3 to 103.6%. Assay
      detection limit was less than 3 micrograms/l. Linearity of the test is given
      throughout the measuring range. There was no interference from bilirubin (up to
      340 mumol/l), haemoglobin (up to 7 g/l), or rheumatoid factor (up to 1,100
      IU/ml). Turbid and lipemic samples interfere. This interference may be avoided by
      pretreating these samples prior to assay. Results correlated well with those
      obtained by an automated ELISA test (r = 0.995) and with those of two commercial
      RIA methods (r greater than 0.97). This latex nephelometric procedure is a
      convenient method and represents an interesting alternative to other immunoassays
      for measuring ferritin in human serum.

PMID- 1403342
TI  - A new sensitive microplate assay of plasma endotoxin.
AB  - We have developed a microplate method for determining endotoxin in platelet-rich
      plasma-using Endospecy, an endotoxin-specific chromogenic Limulus test reagent.
      Nonspecific activators and inhibitors of the test were eliminated by exposing
      samples (5 microliters) to the alkali reagent consisting of KOH, CaCl2, Triton X
      100, ethyleniminepolymer and N,N-bis(2-hydroxyethyl)glycine. The recoveries of
      various endotoxins were almost complete and not enhanced by dilution. The dose
      response curve was linear over endotoxin concentrations of 2-400 pg/ml with good
      precision (C.V. less than 5.0%). Normal human plasmas (n = 30) contained less
      than 5.0 pg/ml of endotoxin in reference to that of Escherichia coli 0111: B4.
      All plasma samples with high concentration of endotoxin by a conventional method
      showed high values by the microplate assay as well. Since it does not require
      centrifugation, the new treatment allows the whole reactions to proceed on the
      same microplate. This permits us to apply the Limulus test to an automated assay
      system, making plasma endotoxin determination simpler and more rapid than a
      conventional test tube method.

PMID- 1403344
TI  - User-defined serum aspartate and alanine aminotransferase, cholesterol,
      triglycerides, urea, and uric acid for the Beckman synchron CX 4/5 using Ames
      Sera-Pak reagents.
AB  - Beckman aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      cholesterol, triglycerides, urea, and uric acid Liquid Reagents for Synchron CX
      4/5 (48, 48, 25, 60, 26, and 30 cents US/test, respectively) are expensive. We
      have established our own methods for serum AST, ALT, cholesterol, triglycerides,
      urea, and uric acid (6, 6, 5, 12, 13, and 6 cents US/test, respectively) using
      Ames Sera-Pak reagents. Linearity of our AST, ALT, cholesterol, triglycerides,
      urea, and uric acid methods were either similar to or higher than the Beckman
      methods. The within run and day-to-day run precisions were acceptable. Recovery
      of our AST, ALT, cholesterol, triglycerides, urea, and uric acid were excellent.
      Our results for AST, ALT, cholesterol, triglycerides, urea, and uric acid
      correlated well with the Beckman results. Bilirubin (340.8 mumol/L) did not
      significantly interfere on our AST, ALT, cholesterol, triglycerides, and urea,
      while its concentrations of 165.8 mumol/L started giving negative interference on
      uric acid. Turbidity (2+) did not interfere significantly on our AST and ALT but
      started giving positive interference on cholesterol, triglycerides, urea, and
      uric acid. Hemolysis (2+) gave positive interference on our cholesterol,
      triglycerides, urea, and uric acid. Stability of Ames Sera-Pak working reagents
      was at least 30 days for AST, ALT, urea, and uric acid and 40 days for
      cholesterol and triglycerides.

PMID- 1403345
TI  - Evaluation of the clinical utility of platelet aggregation studies in the long
      term follow-up of patients with atherosclerotic vascular disease.
AB  - The present study was designed to evaluate the usefulness of laboratory
      monitoring of antiplatelet therapy by means of a multiparametric evaluation of in
      vitro platelet aggregation tests in the attempt to individually optimize a given
      therapeutic regimen. The presence of a condition of hyperaggregability was shown
      in approximately 80% of patients with different forms of atherosclerotic vascular
      disease not undergoing any therapeutic regimen with antiplatelet agents.
      Conversely, a significant decrease in platelet activity was observed in patients
      undergoing different therapies based on acetylsalicylic acid (ASA), ticlopidine,
      or indobufen. The similar antiaggregatory effect of low-dose vs. high-dose ASA
      therapies was also shown. Dipyridamole alone showed no antiaggregatory effect,
      which, in turn, was reached only by the addition of ASA. Nevertheless, the
      association of ASA plus dipyridamole did not show any stronger antiplatelet
      effect than ASA alone. The evaluation of in vitro platelet activity in a group of
      patients treated with picotamide failed to show any significant change in
      comparison with the untreated group, probably due to the short half-life of
      picotamide in man and/or to its capability of reversibly antagonizing the action
      of thromboxane at receptor level. The evaluation of a long-term follow-up of 90
      patients treated with different antiplatelet agents supports the idea that a
      multiparametric analysis of in vitro platelet aggregation may provide valuable
      help in monitoring and optimizing a given therapeutic regimen.

PMID- 1403346
TI  - Determination of aluminum in biological fluids by furnace atomic absorption
      spectrophotometry.
AB  - Detailed procedures were developed for the furnace atomic absorption
      spectrophotometry (FAAS) determination of aluminum (Al) in serum, urine,
      cerebrospinal fluid (CSF), and proportionated dialysate. Of particular note were
      the use of Mg (NO3)2.6H2O as a matrix modifier and the employment of the standard
      additions routine in analysis. The accuracy of the method(s) used is supported by
      work with assayed controls and by recovery studies. The use of a "clean room" was
      shown to be unnecessary. Normal serum, urine, and CSF Al ranges observed were 4.8
      8.9, 5.1-9.1, and 1.0-5.8 micrograms L-1 respectively.

PMID- 1403347
TI  - Contemporary concepts of autoimmunity and autoimmune diseases.
AB  - No single theory or mechanism can explain the phenomenon of autoimmunity and
      autoimmune diseases. Not all autoimmune responses are harmful or "forbidden."
      Considerable research has indicated that autoimmune response may be normal and
      important in the regulation of the immune system. Autoimmunity may play a role in
      a wide range of clinical states including physiological clearance of dead cells,
      and cell components, aging, response to viral and microbial infections, and
      generalized immunological diseases. There are many factors involved in
      autoimmunity including genetic, hormonal, immunological, and environmental
      factors. The susceptibility to autoimmune diseases is multifactorial and
      polygenic. There is a definite association of the autoimmune diseases with MHC
      alleles. Also, non-MHC genes are involved in disease susceptibility. Numerous
      mechanisms of autoimmunity have been discussed. There may be an alteration with
      dysregulation of the immune system with defective generation of normal suppressor
      mechanisms or an altered neuroendocrine regulation. The altered immune system
      will make the host more susceptible to autoimmune disease. Autoimmune reactions
      can occur in a host with a normal immune system. Some examples are as follows: 1.
      Infection or damage to host target organ with release or alteration of
      autoantigen 2. Molecular mimicry or cross-reactivity between virus or bacteria
      and host autoantigens 3. Abnormal expression of MHC molecules by antigen
      presenting cells in target cells resulting in activation of autoreactive T-cells.
      4. Drug administration

PMID- 1403348
TI  - Rapid screening method for polymorphism of group A apolipoproteins.
AB  - Polymorphism of apolipoproteins AI and AII (apo AI and apo AII) can be easily
      investigated in plasma by a simple method involving a 30-min incubation of EDTA
      plasma in the presence of urea, dithiothreitol, and Nonidet P-40 followed by
      subsequent isoelectric focusing (IEF). The sample (2 microL) was applied to an
      ultrathin flat acrylamide gel of pH range 4-6, and focused using a Bio-Rad Mini
      IEF Cell for 1.5 h at a maximum of 500 V. Coomassie Blue R-250 was used to
      visualize the apolipoproteins. To verify the identity of the different
      apolipoproteins after IEF, the gel was immunofixed directly with anti-apo AI, or
      immunoblotted on polyvinylidene difluoride (PVDF) membrane using monospecific
      antibodies to apo AI and apo AII and an anti-immunoglobulin-alkaline phosphatase
      conjugate. High-density lipoprotein (HDL) was used as a standard for Apo AI
      variants. Employing these techniques, human plasma apo AI was resolved into one
      major band (apo AI0, pI 5.54), and four minor bands identified as apo AI+2 (pI
      5.75), apo AI+1 (pI 5.66), apo AI-1 (pI 5.45), and apo AI-2 (pI 5.34). Apo AII
      was resolved into one major isoprotein designated as apo AII0 (pI 4.87), and two
      minor isoforms apo AII+1 and apo AII-1 which focused at pIs of 5.18 and 4.58,
      respectively. The results showed that these methods can be used to identify apo
      AI and AII isoforms without prior ultracentrifugation to isolate the HDL. The
      entire procedure, including IEF, fixation (chemical or immunofixation), and
      staining, can be accomplished in 5 h compared to 2 days using previously reported
      technique.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403349
TI  - Sera from simian immunodeficiency virus-infected rhesus macaques inhibit
      lymphocyte proliferation.
AB  - Rhesus macaque monkeys infected with the simian immunodeficiency virus (SIV)
      develop a syndrome mimicking acquired immunodeficiency syndrome (AIDS) in humans.
      We had demonstrated previously that sera from individuals infected with human
      immunodeficiency virus (HIV) inhibit the proliferation of lymphocytes from
      healthy noninfected subjects and that this phenomenon was associated with the
      development of clinical AIDS. Thus, we sought to determine whether sera from SIV
      infected monkeys would also inhibit lymphocytes from healthy humans and SIV
      negative rhesus monkeys. Sera from SIV-infected monkeys were compared with sera
      from uninfected animals and cultured with cells from healthy human volunteers or
      SIV-negative monkeys in the presence or absence of phytohemagglutinin (PHA). Cell
      proliferation was determined by measuring the incorporation of radiolabeled
      thymidine into cellular DNA. Sera from SIV-infected monkeys suppressed the
      proliferation of human and non-human primate lymphocytes. This activity appears
      to be similar to that described for sera from HIV-1-infected humans. Therefore,
      rhesus macaques infected with SIV provide a model for the study of serum
      inhibitory factors previously reported in AIDS patients.

PMID- 1403350
TI  - Sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for
      (anti-human T-cell leukemia virus type I) IgG in serum using recombinant gag
      p24(14-214) as antigen.
AB  - A sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for
      (anti-human T-cell leukemia virus type I) IgG (anti-HTLV-I IgG) in serum using
      recombinant gag p24(14-214) of HTLV-I is described. The recombinant gag p24(14
      214) is soluble in the absence of detergents and allows the use of enzymes other
      than horseradish peroxidase as a label in the assays. The usefulness of
      recombinant gag p24(14-214) was examined with 305 sera characterized by other
      methods including gelatin particle agglutination, enzyme-linked immunosorbent
      assay (ELISA) using HTLV-I, and Western blotting. This assay was more sensitive
      than other methods using HTLV-I as antigen. The specificity could be tested by
      preincubation of test serum with excess of the recombinant protein. Most of
      negative and positive sera were discriminated. However, some results appeared to
      be false-positive or false-negative, and recombinant gag p24(14-214) was
      suggested to be useful, when used with other recombinant proteins and/or
      peptides, for improving the reliability of serodiagnosis by separately
      demonstrating antibodies against as many different epitopes of HTLV-I as
      possible. Anti-HTLV-I IgG in test serum, which had been incubated with excess of
      inactive beta-D-galactosidase to eliminate interference by anti-beta-D
      galactosidase antibodies, was reacted simultaneously with 2,4-dinitrophenyl
      bovine serum albumin-recombinant gag p24(14-214) conjugate and recombinant gag
      p24(14-214)-beta-D-galactosidase conjugate. The complex formed consisting of the
      three components was trapped onto polystyrene balls coated with affinity-purified
      (anti-2,4-dinitrophenyl group) IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403351
TI  - Impaired cytokine production in whole blood cell cultures from patients with
      colorectal carcinomas as compared to benign colorectal tumors and controls.
AB  - Cytokine production was investigated in whole blood cell cultures from 74
      patients with colorectal carcinomas, 20 patients with benign colorectal tumors,
      and 314 healthy controls. In the 4 day post induction supernatants the levels of
      IFN-gamma, IL-1-alpha, IL-2, and TNF-alpha were measured by a sensitive
      immunoassay. In the blood cell cultures of the patients with colorectal
      carcinomas significantly lower values of IFN-gamma (P less than or equal to
      .001), IL-1-alpha (P less than or equal to .001), and IL-2 (P less than or equal
      to .01) were found as compared to the patients with benign tumors and the
      controls, although total and differential leukocyte counts were similar in all
      three groups. A linear correlation between the levels of IFN-gamma and IL-1-alpha
      and the tumor stages could be shown. Our results suggest that a growing tumor
      burden may induce increasing immunological deficiencies as reflected by a
      decreasing cytokine production of the immune cells.

PMID- 1403352
TI  - G test, a new direct method for diagnosis of Candida infection: comparison with
      assays for beta-glucan and mannan antigen in a rabbit model of systemic
      candidiasis.
AB  - An indirect method to measure beta-glucan, a major structural component of yeast
      cell walls, is available, but has the disadvantage of requiring the combined use
      of two assays. Recent reports describe the fungal index, which measures the
      difference between the conventional limulus test, in which factors C and G react
      with endotoxin and beta-glucan, and a new endotoxin-specific test, in which only
      factor C reacts with endotoxin. The G test was developed as a direct method to
      measure beta-glucan, and contains only factor G reacting with beta-glucan alone.
      In this study, the G test was examined in sera of rabbits with experimental
      systemic candidiasis, and compared with the fungal index and mannan assay. The G
      test showed positive in all rabbits with systemic candidiasis faster and with
      higher titers than with the fungal index. Three rabbits with fulminant systemic
      candidiasis showed higher levels of reactivity with the G test and the fungal
      index than two rabbits with mild reactions. Mannan was positive by at least one
      serum in four of five rabbits by the latex agglutination test, and there was a
      good correlation between these assays. The G test is a good serodiagnostic method
      for the detection of candidiasis.

PMID- 1403353
TI  - Immunoblot assay for detection of autoantibodies in autoimmune disease.
AB  - When detecting antinuclear antibodies (ANA) a similar indirect immunofluorescence
      (IIF) pattern may be produced by antibodies which correspond to different
      antigenic specificity or to diverse autoimmune disorders. To circumvent this
      problem, we used an immunoblotting against total antigen from HEp-2 cells (TA-HEp
      2-C) which proved to be more specific and sensitive than IIF, since it detected
      up to 40 antigenic bands and an immunoblot pattern characteristic of each
      individual and unrelated to the fluorescence patterns of ANA. The analysis of
      immunoblot patterns is of great diagnostic value, since in patients with systemic
      lupus erythematosus (SLE) the antigenic zone is found between 21 and 48 kDa,
      whereas in other rheumatic diseases with or without positive ANA antibodies by
      IIF it is found between 14 and 21 kDa. Bands which appear after 50 kDa may or may
      not have pathological significance since they are present in most normal
      individuals. The use of reference sera allowed the identification in the extract
      of previously described antigens relevant to these diseases. Some patients showed
      bands which have yet to be reported and may be clinically significant on their
      own or in association with other autoantibodies. The long-term follow-up of these
      immunoblot patterns may prove to be of prognostic importance.

PMID- 1403354
TI  - Serum magnesium, copper, and zinc concentrations in acute myocardial infarction.
AB  - This study was carried out to assess the serum levels of magnesium, copper, and
      zinc after an acute episode of myocardial infarction. Determination of the metal
      concentrations were carried out on 41 patients with myocardial infarction and 41
      healthy controls matched for age and sex. A slight decrease in the mean level of
      magnesium (P less than .05) was observed in patients (2.0 mg/dl) compared with
      the controls (2.1 mg/dl). The mean serum copper concentration was significantly
      higher (P less than .001) in patients (138 micrograms/dl) than in controls (98
      micrograms/dl), while the mean serum zinc concentration was significantly lower
      (P less than .001) in patients (75 micrograms/dl) than in controls (100
      micrograms/dl). The differences in serum copper and zinc levels between patients
      and controls were magnified considerably when the copper/zinc ratios were
      calculated for both groups (P less than .001). The mean copper/zinc value
      obtained for patients (1.91) was almost double that for the controls (1.02).

PMID- 1403356
TI  - The pathology of premature ovarian failure.

PMID- 1403355
TI  - Monoclonal antibody-based ELISA to detect glycoprotein tumor-associated-antigen
      specific immune complexes in cancer patients.
AB  - This report describes the development and applicability of a tumor-associated
      antigen-specific immune complex (IC) detection assay to denote the presence of
      tumor cells in a cancer host. This assay utilizes a murine monoclonal antibody,
      AD1-40F4, which was produced to a glycoprotein tumor-associated antigen (TAA). In
      Western blot, the murine monoclonal antibody recognized a 90-100 kD subunit of
      the antigen. This antigen is immunogenic in cancer patients and induces formation
      of endogenous antigen-antibody complexes. Analysis of 250 sera from normal
      individuals and 419 sera from cancer patients revealed that a significantly (P
      less than .0005) greater proportion (234/419; 55.9%) of cancer sera was positive
      for the marker than the normal sera (8/250; 3.2%). The incidence of the 90 kD-TAA
      specific-IC was consistently and significantly higher in melanoma (58.5%; 38/65),
      sarcoma (52.9%; 83/157), and carcinoma of breast (50.9%; 58/114), lung (68.2%;
      30/44), and colon (64.1%, 25/39) than in the normal group. The age of serum
      donors did not affect the incidence of the reactivity. Also, at least in the
      cancer group the gender of the serum donor did not affect the incidence of the 90
      kD-TAA-specific-IC positivity. In a retrospective study where sequential serum
      samples obtained postoperatively from 105 patients with melanoma were analyzed,
      the 90 kD-TAA-specific-IC could be detected in 72 (69%) of patients several years
      before the appearance of clinically detectable disease.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 1403357
TI  - The demonstration of a subset of carcinoid tumours of the appendix by in situ
      hybridization using synthetic probes to proglucagon mRNA.
AB  - Previous studies using immunohistochemistry have shown variable hormone
      production by carcinoid tumours of the appendix. In order to confirm the
      existence of a specific subset of these tumours, in situ hybridization using
      synthetic oligonucleotide probes to detect pre-proglucagon and pre-proinsulin
      mRNA was performed in formalin-fixed, paraffin-embedded material from eight
      tubular carcinoids, 12 insulin carcinoids, and two mucinous carcinoids. The
      results were correlated with standard silver and mucin stains. All tubular
      carcinoids but none of the insular or mucinous carcinoids contained proglucagon
      mRNA. Proinsulin mRNA was not detected in any of the tumours. Tubular carcinoids
      of the appendix constitute a definable subset of appendiceal carcinoids which
      have a similar distribution and prognosis to typical insular carcinoids and can
      be diagnosed on haematoxylin and eosin-stained sections confirmed by routine
      special stains. The main need for recognition is to avoid confusion with mucinous
      carcinoids, which have a worse prognosis and may require more aggressive
      treatment.

PMID- 1403358
TI  - TDM35--a new monoclonal antibody to the XH1 cervical carcinoma cell line.
      Characterization and immunoperoxidase localization in benign and malignant
      tissues.
AB  - The murine monoclonal IgG1 kappa antibody TDM35 was raised against the cervical
      carcinoma cell line XH1. The antibody recognizes 18.5-66 kDa NCA-like
      glycoproteins and immunostains a variety of formalin-fixed, paraffin-embedded
      normal, benign, and malignant tissues. It is of value in the diagnosis of
      carcinoma of the exocrine pancreas and it identifies foci of squamous and
      glandular differentiation in other tumours. TDM35 should form a useful addition
      to a panel of antibodies for the evaluation of epithelial lesions.

PMID- 1403359
TI  - Oral contraceptive use and histopathology of cancerous breasts in young women.
      Members of the U.K. National Case-Control Study Group.
AB  - A retrospective histopathological study of 300 women under 36 years of age was
      carried out to determine whether breast cancers occurring in oral contraceptive
      users showed any differences in pathological features compared with non-users.
      The patients belong to an age group in which an increased risk of cancer
      development has been reported following oral contraceptive usage. The incidence
      of non-neoplastic conditions in the residual breast was also studied in the two
      groups. There was little difference between breast cancers arising in pill users
      and non-users but in the residual non-neoplastic breast a decreased incidence of
      cysts and blunt duct adenosis was found in current users of the contraceptive
      pill. In contrast, lactational foci were found only in the breasts of pill users.
      The incidence of intraductal hyperplasia was not significantly different in the
      two groups.

PMID- 1403360
TI  - Flow cytometric DNA-histogram analysis: non-stoichiometric fluorochrome binding
      and pseudoaneuploidy.
AB  - Detection of aneuploid subpopulations using flow cytometry requires
      stoichiometric binding of nucleic acid-specific fluorochromes onto DNA. It is
      shown that parameters like cell type specificity and differentiation stage, cell
      cycle stage, loss of DNA-integrity, cell preparation, and cytochemistry affect
      fluorochrome binding to DNA and give rise to the appearance of pseudo-aneuploid
      cell populations. Intercalating as well as non-intercalating fluorochromes show
      non-stoichiometric DNA-labelling in cell populations with identical DNA content,
      and pseudo-aneuploidy was found in flow cytometers equipped with either arc lamps
      or argon lasers. Pseudo-aneuploidy was never observed with intercalating and non
      intercalating fluorochromes within identical specimens, consisting of cells of
      various differentiation states (e.g., bone marrow) or containing large numbers of
      dead cells. Therefore, fluorochromes exhibiting different base-pair specificities
      or steric binding modes should be applied to be sure of the correct
      interpretation of small levels of hypo- or hyper-diploidy (+/- 20 per cent).

PMID- 1403361
TI  - Pathogenesis of pancreatic perilobular necrosis in patients with liver disease.
AB  - We often see perilobular necrosis of the pancreas in patients with liver disease
      at autopsy. This study was undertaken to determine the frequency and the
      mechanism of development of pancreatic perilobular necrosis in patients with
      liver disease. Pancreatic perilobular necrosis was seen in 21 per cent of 261
      autopsied patients: in 41 per cent of 73 autopsied patients with liver disease
      and in 13 per cent of 188 autopsied patients without liver disease. Moreover,
      splanchnic congestion was present in 90 per cent of 30 pancreatic perilobular
      necrosis patients with liver disease. These data indicate that patients with
      liver disease develop perilobular necrosis of the pancreas more often than
      patients without liver disease, and that the high frequency may be a sequela of
      splanchnic congestion; that is, congestion of the pancreas and endotoxaemia due
      to congestion of the gut.

PMID- 1403362
TI  - Collagen fibril structure of normal, aging, and osteoarthritic cartilage.
AB  - The collagen architecture in normal, aging, and osteoarthritic articular
      cartilage was studied optically using a new silver staining technique based on
      specimens from 50 autopsy cases, four amputated limbs, and six osteoarthritic
      knees. In the normal articular cartilage, the collagen fibrils in the superficial
      zone were compactly arranged into layers of decussating flat ribbons mostly
      parallel to the artificial split lines. The fibrils showed a tendency to condense
      into vertical arcade columns undergirded by tangential bundles in the
      intermediate zone. In the deep zone, the fibrils formed a random meshwork with a
      slight preponderance of vertical fibrils in the perilacunar region. Three types
      of early degradative lesions involving the collagen network were identified. Type
      I lesions consisted of focal superficial disruptions related to age and friction.
      Type II lesions consisted of focal disruptions of tangential fibrils in the
      intermediate zone leading to cyst formation, probably representing a form of
      local stress failure. Type III lesions were found in the patella and consisted of
      marked swelling of the superficial zone, the cause of which was unknown. Lesions
      of varying severity were seen within each of the three types; the morphological
      changes of the more severe lesions overlapped with those of clinically overt
      osteoarthritis.

PMID- 1403363
TI  - Nucleolar organizer regions in mesothelial proliferations.

PMID- 1403364
TI  - Transient absorption spectra and quenching of coumarin excited states by nucleic
      acid bases.
AB  - Triplet-triplet absorption spectra of coumarin show different profiles and maxima
      in ethanol from those in water, which are very similar to those reported in
      benzene. Long-lived transient species other than triplet states were generated as
      initial photoproducts between coumarins and nucleic acid bases. The excited
      singlet and triplet states of coumarins were quenched by nucleic acid bases.
      Adenine base quenched the excited singlet state of coumarins more efficiently
      than thymine base. However, photocycloadducts of furocoumarins are formed
      predominantly with thymine, and not with adenine. Moreover, it is reported that
      the poly[dA-dT].poly[dA-dT] sequence region is the most favourable site for the
      photocycloaddition reaction of furocoumarins. The results imply that adenine
      contributes to singlet-state photocycloaddition reaction of furocoumarins with
      thymine, probably through an adenine-furocoumarin-thymine termolecular
      interaction.

PMID- 1403365
TI  - Photochemical release of bases from nucleosides and their derivatives by water
      soluble iron(III) porphyrins.
AB  - The compounds [meso-tetrakis(1-methyl-4-pyridiniumyl)porphyrinato]iron(III )
      (FeIIITMPyP) and [meso-tetrakis(3,5-dichloro-1-methyl-4-pyridiniumyl)porphyrinat
      o]iron(III) (FeIIITCl2MPyP) photocatalysed the release of bases from nucleosides
      and their derivatives. The ribonucleosides, of which cytidine (C) gave the
      highest yield, produced much higher yields of free base than the corresponding
      deoxyribonucleosides. Under an argon atmosphere, virtually quantitative reduction
      of FeIIITMPyP into FeIITMPyP by C or 2'-deoxycytidine (dC) was observed and the
      reduction by C was much more effective than by dC. The increased reactivity of
      ribonucleosides relative to deoxyribonucleosides was ascribed to a difference in
      the binding properties of the porphyrin-nucleoside interactions and to base
      releasing degradation of ribonucleosides from their C-2' carbon radical.

PMID- 1403366
TI  - The laws of delayed photohaemolysis sensitized by chlorin e6.
AB  - The relationships between the rate of post-irradiated photohaemolysis sensitized
      by chlorin e6 and parameters such as the light fluence (time of irradiation) and
      sensitizer concentration were studied. On the basis of the single-parametric
      approach proposed by Valenzeno and Pooler, it was found that the haemolytic rate
      varies with the square of both the light fluence and the sensitizer
      concentration. Thus it can be concluded that, in a single erythrocyte lesion, two
      chlorin e6 molecules participate, each absorbing one photon. The possibility of
      suppression of post-irradiation haemolysis was also studied using the lipophilic
      antioxidant, butylated hydroxytoluene (BHT), and scavengers of 1O2, O2.- and HO.
      radicals. It was found that BHT inhibits, to a considerable extent, the post
      irradiation lysis of cells, by about a factor of 2.5 at a BHT concentration of 9
      microM. The addition to the medium of NaN3 (a scavenger of 1O2), superoxide
      dismutase (a scavenger of O2.- radicals), ethanol and D-mannitol (scavengers of
      HO. radicals), when irradiation was interrupted, did not produce a marked
      influence on the kinetics of subsequent haemolysis. On the basis of the results
      obtained, the nature of erythrocyte targets, which are crucial for the
      photodynamic effect of chlorin e6, is discussed.

PMID- 1403367
TI  - Retinal photoisomerase: role in invertebrate visual cells.
AB  - In invertebrate visual cells, the rhodopsin content is maintained at a high level
      by the fast process of photoregeneration during daylight. Rhodopsin is converted
      by photoabsorption to metarhodopsin, which is reconverted to rhodopsin by light.
      In addition, rhodopsin is regenerated by a slow process of renewal which takes
      days to complete and involves the biosynthesis of opsin. It is well known that
      rhodopsin can be formed from opsin only when 11-cis-retinal is present; this
      requires the existence of an isomerizing enzyme which is capable of transforming
      all-trans-retinal, released from the degradation of metarhodopsin, into the 11
      cis-retinal isomer. In some invertebrate visual systems, experiments on rhodopsin
      regeneration have been interpreted by assuming that the isomerization reaction is
      a light-dependent process involving a retinal-protein complex. Two retinal
      photoisomerases which have been well characterized, i.e. bee photoisomerase and
      cephalopod retinochrome, are reviewed here. Their properties are compared in
      order to determine their physiological role, which is likely to be in the renewal
      of visual pigment rhodopsin. To conclude, a visual pigment cycle is proposed in
      which rhodopsin regeneration follows two light-dependent pathways. This greatly
      simplifies the rhodopsin regeneration scheme for invertebrate visual systems.

PMID- 1403369
TI  - Synergistic effects of photoactivated tetra(4-sulfonatophenyl)porphine and
      nocodazole on microtubule assembly, accumulation of cells in mitosis and cell
      survival.
AB  - Human carcinoma cells of the line NHIK 3025 were incubated with meso-tetra(4
      sulfonatophenyl)porphine (TPPS4) for 18 h and exposed to light in the absence or
      presence of nocodazole. Nocodazole (1 microgram ml-1) was applied to the cells 15
      min prior to light exposure and washed off the cells immediately afterwards. The
      presence of nocodazole during photoactivation of TPPS4-loaded cells leads to a
      significantly reduced ability of tubulin to repolymerize after withdrawal of
      nocodazole, an increased accumulation of the cells in mitosis with a larger
      fraction in c-metaphase and a higher yield of photoactivated cells. A higher
      proportion of the cells accumulating in mitosis 6-12 h after exposure to light is
      unable to form colonies when exposed to light in the presence of nocodazole than
      in its absence. The present results are consistent with a specific TPPS4-induced
      photodamage to the unpolymerized form of the microtubule components.

PMID- 1403368
TI  - Photodynamic activity of chlorin e6 and chlorin e6 ethylenediamide in vitro and
      in vivo.
AB  - Several parameters of chlorin e6 and its derivative chlorin e6 ethylenediamide
      have been investigated as these compound are potential sensitizers for
      photodynamic therapy. A study carried out to compare the cellular uptake of the
      pigments indicates that chlorin e6 ethylenediamide possesses an enhanced affinity
      for tumour cells and cellular membranes. Comparison of the uptake in induced
      sarcoma shows that chlorin e6 ethylenediamide is a much better tumour localizer
      than chlorin e6. The efficiency of phototherapy with chlorin e6 ethylenediamide
      is higher than that with chlorin e6. These data show the influence of the
      substitution of the carboxyl groups in chlorin e6 by ester and amide groups on
      the photosensitizing properties of the pigments.

PMID- 1403370
TI  - Phototoxicity of non-steroidal anti-inflammatory drugs: in vitro testing of the
      photoproducts of Butibufen and Flurbiprofen.
AB  - In this work, the phototoxicity of two non-steroidal anti-inflammatory drugs,
      Butibufen and Flurbiprofen, was examined. Both were unstable to light, to give
      several photoproducts which were isolated and identified. The different
      photoproducts were formed by a primary photochemical mechanism which involves an
      initial cleavage of the C-C bond alpha to the carbonyl group, followed by several
      secondary processes. The cytotoxic effects of the xenobiotics were evaluated
      using two well-established biological in vitro tests: (a) enzyme leakage lactate
      dehydrogenase and glutamate-oxaloacetate transaminase from cultured fibroblasts
      and (b) lysis of red blood cells. The benzylic alcohols caused extensive leakage
      from cultured fibroblasts at the different concentrations assayed. The alcohol
      obtained from Butibufen was a potent lytic agent for human red blood cells. The
      other photoproducts, Butibufen and Flurbiprofen did not produce observable toxic
      effects on cells.

PMID- 1403371
TI  - Action spectra revisited.

PMID- 1403372
TI  - Is interdisciplinarity only a pitiful utopia?

PMID- 1403373
TI  - Endogenous protoporphyrin IX, a clinically useful photosensitizer for
      photodynamic therapy.
AB  - The tissue photosensitizer protoporphyrin IX (PpIX) is an immediate precursor of
      heme in the biosynthetic pathway for heme. In certain types of cells and tissues,
      the rate of synthesis of PpIX is determined by the rate of synthesis of 5
      aminolevulinic acid (ALA), which in turn is regulated via a feedback control
      mechanism governed by the concentration of free heme. The presence of exogenous
      ALA bypasses the feedback control, and thus may induce the intracellular
      accumulation of photosensitizing concentrations of PpIX. However, this occurs
      only in certain types of cells and tissues. The resulting tissue-specific
      photosensitization provides a basis for using ALA-induced PpIX for photodynamic
      therapy. The topical application of ALA to certain malignant and non-malignant
      lesions of the skin can induce a clinically useful degree of lesion-specific
      photosensitization. Superficial basal cell carcinomas showed a complete response
      rate of approximately 79% following a single exposure to light. Recent
      preclinical studies in experimental animals and human volunteers indicate that
      ALA can induce a localized tissue-specific photosensitization if administered by
      intradermal injection. A generalized but still quite tissue-specific
      photosensitization may be induced if ALA is administered by either subcutaneous
      or intraperitoneal injection or by mouth. This opens the possibility of using ALA
      induced PpIX to treat tumors that are too thick or that lie too deep to be
      accessible to either topical or locally injected ALA.

PMID- 1403374
TI  - Dark induction of haem oxygenase messenger RNA by haematoporphyrin derivative and
      zinc phthalocyanine; agents for photodynamic therapy.
AB  - Haematoporphyrin derivative is one of the main drugs currently used in clinical
      trials involving photodynamic therapy of cancer, and zinc phthalocyanine is being
      considered as one of several possible alternatives. We show that incubation of
      cultured human fibroblasts populations with either of the two drugs will lead to
      a sharp increase in the accumulation of the messenger RNA corresponding to haem
      oxygenase. Only cells incubated with haematoporphyrin derivative show additional
      enhancement of expression of this specific gene on exposure to red light. Since
      haem oxygenase induction appears to be a specific stress response that may be
      involved in cellular defence, such observations should be confirmed under
      conditions which would allow the clinical implications to be fully evaluated.

PMID- 1403375
TI  - Excited singlet state properties of anthracenedione photosensitizers.
AB  - The absorption, fluorescence and S1 state kinetics of anthracycline antitumour
      drugs (e.g. daunomycin, adriamycin) and several imino- and/or amino-substituted
      derivatives are investigated. The study, which includes all anthracyclines which
      possess photocytocidal activity, is extended to the disubstituted
      aminoanthracenedione, mitoxantrone, a red-light-absorbing antitumour drug whose
      activity, both in vitro and in vivo, is enhanced by photoactivation. The S1 state
      of the anthracycline imino and amino derivatives, in aqueous buffer at pH 7.4, is
      characterized by bi-exponential decay kinetics which indicates the presence of
      two ground state populations differing in the extent of hydrogen bonding. The
      ammonium group of the sugar moiety of anthracyclines contributes to the quenching
      of the S1 state population through a prototropic mechanism.

PMID- 1403376
TI  - Ferric-ion-photosensitized damage to DNA by hydroxyl and non-hydroxyl radical
      mechanisms.
AB  - Iron(III) and UVA (320-400 nm) light strongly diminished the transforming
      activity of Haemophilus influenzae DNA in the presence of oxygen. Iron(III) alone
      in the absence of light had no measurable effect on the transforming activity.
      The chelating agent ethylenediaminetetraacetic acid (EDTA) conferred virtually
      complete protection, but hydroxyl radical scavengers (mannitol, methanol,
      ethanol, isopropanol and dimethyl sulfoxide) inhibited only a small fraction of
      the inactivation. Treatment of plasmid DNA (pBR322) with iron(III) results in the
      conversion of the covalently closed circular form of the plasmid to open circles
      and ultimately to the linear form. Concomitant with the alteration in the
      conformation of the plasmid, the ability to transform Escherichia coli was
      reduced. In model systems, iron(III) photoreacted with the DNA backbone causing
      nicking and double-strand breakage. The results are consistent with a mechanism
      involving a preliminary complexation of iron(III) by DNA followed by the
      generation of reactive free radicals other than .OH. We suggest that bound iron,
      or other UV-absorbing transition metal complexes, may be chromophores capable of
      causing DNA damage in the long-wave near-UV region.

PMID- 1403377
TI  - Ultrastructural damage in photosensitized endothelial cells: dependence on
      hematoporphyrin delivery pathways.
AB  - The subcellular photodamage to endothelial cells in culture, revealed by
      transmission electron microscopy, was correlated with discrete delivery pathways
      of hematoporphyrin (HP). Cell detachment from the extracellular matrix, prominent
      water influx starting at the outer membrane and formation of blebs followed by
      cell death were the result of photodynamic damage induced by aqueous HP. Serum
      bound HP was internalized by endocytosis and accumulated in lysosomal
      compartments as located after photosensitization. Obstructed lysosomal membranes,
      degradation of chromatin and swelling of endoplasmic reticulum were revealed in
      these cells. Red blood cells (RBCs), preincubated with HP, delivered low amounts
      of the drug to endothelial cells. The photodamage was limited to the nucleus and
      nucleolus. The role of photosensitizer delivery pathways in cancer cell damage is
      discussed.

PMID- 1403378
TI  - Mode of photocatalytic bactericidal action of powdered semiconductor TiO2 on
      mutans streptococci.
AB  - Powdered semiconductor TiO2 has a photocatalytic bactericidal capacity on some
      kinds of bacteria, but its mechanism still remains unclear. The mode of its
      photocatalytic bactericidal action on the mutans group of streptococci was
      investigated. Powdered TiO2 had a bactericidal capacity on all serotypes of
      mutans streptococci. Streptococcus sobrinus AHT was mainly used for these
      experiments. The most effective concentration of TiO2 was about 1 mg ml-1 and, at
      this concentration, 10(5) colony-forming units of S. sobrinus AHT per millilitre
      were completely killed within 1 min. In order to search for the mechanism of this
      effect, a high bacterial cell density (10(9) colony-forming units ml-1) was used
      in the following studies. "Rapid" leakage of potassium ions from the bacteria
      occurred parallel to the decrease in cell viability. Protein and RNA were
      "slowly" released from bacterial cells for a reaction time up to 120 min. The pH
      of the reaction mixture decreased continuously to 4.5 after 120 min. Co
      aggregation of S. sobrinus AHT and powdered TiO2 occurred at high bacterial
      densities (above 10(8) colony-forming units ml-1). Aggregates gradually
      decomposed with light irradiation. Transmission electron microscopy of S.
      sobrinus AHT after photocatalytic action for 60-120 min indicated complete
      destruction of bacterial cells. From these results, bacterial death appears to be
      caused by a significant disorder in cell membranes and finally the cell walls
      were decomposed.

PMID- 1403379
TI  - Assessment of the partitioning of probes to membranes by spectroscopic titration.

PMID- 1403380
TI  - Respiratory syncytial virus puzzle: clinical features, pathophysiology,
      treatment, and prevention.

PMID- 1403382
TI  - Role of immunoglobulin subclasses and specific antibody determinations in the
      evaluation of recurrent infection in children.
AB  - We studied humoral immune function in 267 children with recurrent respiratory
      infections referred to our immunology clinic to determine the most appropriate
      immunologic studies for evaluating recurrent infections in children. Of this
      highly selected population, 58% had a partial deficiency in one or more of the
      major immunoglobulin isotypes or IgG subclasses (defined as at least 2 SD below
      the normal age-adjusted mean). In none of the patients was there a total absence
      of an immunoglobulin isotype. The most common abnormality was partial IgA
      deficiency, which was found in one third of the patients. Twenty-six patients had
      only partial IgG subclass deficiencies, of which 20 were deficiencies of a single
      subclass. IgG1 was an isolated partial defect in three patients, IgG3 in five
      patients, and IgG2 and IgG4 were selective partial defects in six patients each.
      Tetanus toxoid and pneumopolysaccharide type 3 were the most immunogenic of the
      immunogens tested; hyporesponsiveness to pneumococcal polysaccharide types 7, 9,
      and 14 was common. Nineteen percent of the patients with normal immunoglobulin
      concentrations who were tested had lower-than-expected antibody titers; 42% of
      those tested with partial isotype deficiencies had deficient antibody responses.
      Of 25 patients with selective partial IgG subclass deficiencies or combined IgG
      subclass deficiencies, eight had antibody deficiencies. Our findings indicate
      that a high proportion of children referred to immunology clinics for recurrent
      infection have a demonstrable immunologic abnormality. Selective IgG subclass
      deficiency or a combined IgG subclass deficiency without an associated deficiency
      in a major immunoglobulin isotype is unusual. Identification of such patients is
      not predictive of the capacity to form antibodies to the antigens tested in this
      study and, in our opinion, adds little to the initial evaluation of immune
      function in such children.

PMID- 1403381
TI  - Laryngotracheobronchitis as a complication of measles during an urban epidemic.
AB  - OBJECTIVE: To evaluate demographic and clinical correlates of
      laryngotracheobronchitis (LTB) as a complication of measles during a community
      wide epidemic. DESIGN: Retrospective review of medical records. SETTING:
      Childrens Hospital Los Angeles, a large urban pediatric facility, during a
      regional epidemic of measles studied January through June 1990. PATIENTS: All
      patients identified at our hospital who met Centers for Disease Control criteria
      for measles. MEASUREMENTS AND RESULTS: Of 440 patients with measles, 82 also had
      LTB (18.6%). Patients in whom LTB developed were significantly younger (mean +/-
      SD: 14.7 +/- 8.2 months) than the cohort (24.8 +/- 30.1 months) (p less than
      0.001) and more likely to require hospitalization (91.5%) than the cohort (44.3%)
      (p less than 0.001). Thirteen patients (17.3%) required intensive care, including
      9 (11%) who required endotracheal intubation for a mean of 8.3 +/- 7.1 days.
      Pulmonary function testing of five patients with an endotracheal tube in place,
      including three not clinically assessed as having pneumonia, indicated the
      presence of concomitant lower respiratory tract disease. CONCLUSION:
      Laryngotracheobronchitis was a frequent and often severe complication of measles.
      The likelihood that LTB would develop was inversely related to age, generally
      required inpatient care, and necessitated endotracheal intubation in severely
      affected patients.

PMID- 1403383
TI  - Antibody response to Bordetella pertussis antigens after immunization with
      American and Canadian whole-cell vaccines.
AB  - Because of apparent differences in the incidence and epidemiology of pertussis in
      the United States and Canada, we measured the antibody response to four
      Bordetella pertussis antigens and to a whole-bacteria preparation in children
      immunized with American and Canadian whole-cell pertussis vaccines. All infants
      received combined pertussis, tetanus, and diphtheria vaccines from one of two
      American manufacturers or a single Canadian manufacturer. The Canadian children
      received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as
      a separate injection, or a product that combined inactivated poliomyelitis
      vaccine with diphtheria, tetanus, and pertussis components. The Canadian
      trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus
      vaccine induced lower anti-pertussis toxin antibody titers than did the American
      vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer
      membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian
      children immunized with inactivated poliomyelitis vaccine either as a separate
      injection or as a combined diphtheria, tetanus, and pertussis vaccine had
      consistently lower pertussis antibody titers than did those who received oral
      poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of
      antibody responses to B. pertussis antigens after immunization with various whole
      cell pertussis vaccines, and that these responses may be influenced by concurrent
      administration of other vaccines.

PMID- 1403384
TI  - Evaluation of gonadotropin responses to synthetic gonadotropin-releasing hormone
      in girls with idiopathic hypopituitarism.
AB  - We hypothesized that prepubertal girls with gonadotropin deficiency would produce
      less follicle-stimulating hormone (FSH) in response to synthetic gonadotropin
      releasing hormone (GnRH) than would gonadotropin-sufficient children. To test
      this hypothesis, we performed 103 GnRH tests serially in 21 children who had
      idiopathic hypopituitarism with growth hormone deficiency. We tried to predict
      whether puberty would occur in the 17 girls with bone ages of 8 years or less. Of
      these 17 girls, 4 failed to have spontaneous secondary sexual characteristics by
      age 16 1/2 years, and 12 had spontaneous complete pubertal development. One girl
      had incomplete pubertal maturation with partial gonadotropin deficiency; her
      results were combined with those of the girls who had no spontaneous pubertal
      development. With increasing bone age, the girls with complete pubertal
      development had a decrease in the increment of FSH released in response to GnRH,
      although basal gonadotropin concentrations did not change. For GnRH tests
      performed at bone ages of 8 years or less, basal luteinizing hormone (LH) values
      did not differ between girls with complete puberty and those with absent or
      incomplete puberty. However, basal FSH and the incremental response of LH and FSH
      to GnRH were greater in those with complete puberty. Only two girls with
      prepubertal bone ages at the time of testing, who subsequently had complete
      puberty, had incremental FSH responses to GnRH that were less than 5 IU/L.
      Individual incremental LH responses to GnRH did not discriminate well between
      groups. None of the girls with adrenocorticotropic hormone deficiency, either
      originally or subsequently, had spontaneous puberty, but 4 of 12 girls with
      thyrotropin deficiency, either originally or subsequently, had complete puberty.
      We conclude that a significant increase in GnRH-stimulated FSH suggests that
      spontaneous pubertal development will occur in girls with idiopathic
      hypopituitarism. However, a low FSH response to GnRH may not be diagnostic of
      gonadotropin deficiency.

PMID- 1403385
TI  - Thiamine, riboflavin, and pyridoxine deficiencies in a population of critically
      ill children.
AB  - The unexpected autopsy finding of Wernicke encephalopathy in three children who
      died after prolonged enteral feeding prompted us to examine the incidence of
      thiamine deficiency in three high-risk pediatric populations. We also measured
      riboflavin and pyridoxine activity in the same groups. We used activated enzyme
      assays (erythrocyte transketolase, glutathione reductase, aspartate
      aminotransferase) to assess tissue stores of the dependent vitamin cofactors
      (thiamine (vitamin B1), riboflavin (vitamin B2), and pyridoxine (vitamin B6),
      respectively). Using our own reference ranges based on data from 80 healthy
      adults and children, we prospectively investigated the B vitamin status of three
      groups of children: (1) 27 patients who were fed solely by nasogastric tube for
      more than 6 months, (2) 80 children admitted to a pediatric intensive care unit
      for more than 2 weeks, and (3) 6 children receiving intensive chemotherapy. The
      upper limits for stimulated enzyme activity in control subjects were unaffected
      by age or gender (16% for transketolase, 63% for glutathione reductase, 123% for
      aspartate aminotransferase). Using these limits, 10 (12.5%) of 80 patients
      receiving intensive care and 4 of 6 patients receiving chemotherapy were thiamine
      deficient. Elevated levels returned to normal after thiamine supplementation. No
      patients were pyridoxine deficient, but 3 (3.8%) of the 80 patients receiving
      intensive care and 1 of the 6 patients receiving chemotherapy were also
      riboflavin deficient. We conclude that unrecognized thiamine deficiency is common
      in our pediatric intensive care and oncology groups. This potentially fatal but
      treatable disease can occur in malnourished patients of any age and is probably
      underdiagnosed among chronically ill children. Our findings may be applicable to
      other high-risk pediatric groups.

PMID- 1403386
TI  - Communicating medical bad news: parents' experiences and preferences.
AB  - Parents (N = 189) of children enrolled in 15 developmental day care centers
      completed questionnaires that examined the experience of being told bad news and
      elicited preferences for physician behavior in a hypothetical situation
      (communicating the diagnosis of Down syndrome). Parents, in comparison with their
      experiences, preferred (p < 0.001) more communication of information and feelings
      by their physician. Their strongest preferences were for physicians to show
      caring (97%), to allow parents to talk (95%), and to allow parents to show their
      own feelings (93%). They wanted physicians to share information (90%) and to be
      highly confident (89%). Most parents (87%) desired parent-to-parent referral, but
      only a few (19%) were referred. We conclude that there is a difference between
      what parents experience and what they desire in physicians who communicate bad
      news. Physicians control the interaction and are highly confident, but parents
      especially value physicians who show caring and allow parents to talk and share
      their feelings.

PMID- 1403387
TI  - Participation in biomedical research: the consent process as viewed by children,
      adolescents, young adults, and physicians.
AB  - We examined the capacity of children, adolescents, and young adults to assent and
      consent to participation in biomedical research, and what physician-investigators
      believe is important for patients in these age groups to know about such
      participation. The sample included 44 male and female subjects, ranging in age
      from 7 to 20 years, who were hospitalized to treat either pediatric cancer or
      obesity. The participants completed a structured interview that assessed
      knowledge of research participation using the elements outlined in the federal
      guidelines for informed consent. The study subjects were most knowledgeable about
      those elements of consent that assessed concrete information (e.g., freedom to
      ask questions, time elements involved, and the benefits of participation). They
      were less knowledgeable about those elements of informed consent that assessed
      abstract information (e.g., scientific vs therapeutic purpose of the study, and
      alternative treatments). Chronologic age was not related to knowledge of the
      elements of informed consent. The strategies that the study subjects used to
      reason about participation in research appeared to parallel their reasoning about
      other physical phenomena.

PMID- 1403389
TI  - Initial observations of human dermatosparaxis: Ehlers-Danlos syndrome type VIIC.
AB  - We describe initial observations of an infant with dermatosparaxis (another form
      of Ehlers-Danlos syndrome, designated as type VIIC), an autosomal recessive
      disorder characterized by skin fragility and described in several species of
      domesticated animals. Electron microscopic examination of the skin shows collagen
      sheets rather than fibrils, and characteristic distortions resembling
      hieroglyphs. In addition to skin fragility, the disorder is characterized by
      redundant skin folds and edema, healing with minimal scar formation, large
      fontanels and wide sagittal and metopic sutures, blue sclerae, micrognathia, and
      umbilical hernia; after the neonatal period there are joint laxity, growth
      failure, short limbs, and normal mineralization of the skeleton except for the
      cranial vault. This disorder may also be a cause of premature rupture of
      placental membranes and myopia.

PMID- 1403388
TI  - Atypical features of the hepatic form of carnitine palmitoyltransferase
      deficiency in a Hutterite family.
AB  - We describe hepatic carnitine palmitoyltransferase (CPT I) deficiency in three
      children (a brother and sister and their second cousin) from an extended inbred
      Hutterite kindred. The patients were first seen between 8 and 18 months of age
      with recurrent episodes of hypoketotic hypoglycemia accompanied by a decreased
      level of consciousness and hepatomegaly. One patient had two Reye syndrome-like
      episodes. Abnormal organic acids were rarely detected in urine. Serum total and
      free carnitine levels were elevated in all three patients. Fibroblast acyl
      coenzyme A dehydrogenase activities were normal in all, but palmitic acid
      oxidation, performed in fibroblasts from one patient, was less than 10% of
      control values. Activity of CPT I in cultured skin fibroblasts from the three
      patients was 10% to 15% of control levels; CPT II activity was normal. Activity
      of CPT I and CPT II in muscle from one patient was normal. Atypical features in
      two of these patients were greatly elevated levels of liver enzymes and creatine
      kinase during acute episodes. The patients have recently been successfully
      treated with medium-chain triglycerides and avoidance of fasting. Early
      identification and treatment of this disorder may avert potentially fatal
      episodes of hypoglycemia.

PMID- 1403390
TI  - Prevention of rheumatic fever in Costa Rica.
AB  - During the beginning of the 1970s, major changes occurred in Costa Rica in the
      treatment of streptococcal throat infections. Because of poor compliance with
      regimens using orally administered agents, intramuscular administration of
      benzathine penicillin was selected as the standard treatment and throat cultures
      were eliminated as a prerequisite for prescribing antibiotics. A decline in the
      incidence of rheumatic fever then occurred. We believe that similar health
      intervention could be applied in other developing countries.

PMID- 1403391
TI  - Chronic hepatitis B in adopted Romanian children.
AB  - Four of five Romanian orphans adopted by U.S. families were found to have chronic
      hepatitis B virus (HBV) infection after negative test results were reported in
      Romania before adoption. Another child with known HBV infection was found to be
      coinfected with hepatitis D virus. There is a high incidence of HBV infection in
      Romanian orphans, and results of tests for HBV are unreliable in Romania.

PMID- 1403392
TI  - Bacillary angiomatosis in a child undergoing chemotherapy.
AB  - Bacillary angiomatosis is an infectious disease of the skin and viscera
      characterized by vascular lesions, originally described in patients with human
      immunodeficiency virus infection. There are also case reports of bacillary
      angiomatosis occurring in immunocompetent patients and in noninfected patients
      with suppressed immune function. We report a case of bacillary angiomatosis in a
      child undergoing chemotherapy for acute leukemia.

PMID- 1403393
TI  - Erythrocyte macrocytosis in infants and children with Down syndrome.
AB  - Erythrocyte mean corpuscular volume and mean corpuscular hemoglobin levels were
      higher in children with Down syndrome than in normal control subjects. Reference
      values for mean corpuscular volume and mean corpuscular hemoglobin level derived
      from normal populations may be inappropriate for children with Down syndrome.
      These findings may have important implications for the diagnosis of iron
      deficiency in these children.

PMID- 1403394
TI  - Intellectual development at age 12 years of children with congenital
      hypothyroidism diagnosed by neonatal screening.
AB  - Twenty-seven patients with congenital hypothyroidism diagnosed by neonatal
      screening were examined at the age of 12 years. The 12 patients with severe
      hypothyroidism at diagnosis (thyroxine < 2 micrograms/dl (< 26 nmol/L), and area
      of-the-knee epiphyses < 0.05 cm2 had a lower IQ than the 15 patients with less
      severe hypothyroidism (mean +/- SD, 89 +/- 17 vs 104 +/- 10; p < 0.007).
      Comparisons of patients and siblings confirm that this difference was due to the
      severity of hypothyroidism.

PMID- 1403395
TI  - Emergence of optic pathway gliomas in children with neurofibromatosis type 1
      after normal neuroimaging results.
AB  - We report the appearance of gliomas of the optic nerve or chiasm in four young
      children with neurofibromatosis type 1 whose previous neuroimaging studies showed
      no abnormalities; the age range of the children was 1 year 8 months to 5 years 9
      months at the time the tumors were detected. Normal neuroimaging findings in an
      infant or young child with neurofibromatosis type 1 does not provide assurance
      that the optic nerves and chiasm will remain healthy.

PMID- 1403396
TI  - Marrow transplantation for thrombocytopenia-absent radii syndrome.
AB  - A two-year-old girl with thrombocytopenia-absent radii syndrome underwent
      transplantation of allogeneic bone marrow from her histocompatible sibling to
      correct her persistently low platelet count. Six years after transplantation, she
      has durable engraftment of allogeneic marrow and a normal platelet count that
      will allow her to undergo necessary corrective orthopedic procedures.

PMID- 1403397
TI  - Effectiveness of dexamethasone in preventing extubation failure in preterm
      infants at increased risk for airway edema.
AB  - We studied 50 preterm infants who had multiple or traumatic endotracheal
      intubations, or whose duration of endotracheal intubation was > or = to 14 days,
      and who were considered at high risk for airway edema. These infants were
      enrolled in a prospective, randomized, controlled clinical trial to assess
      whether prophylactic dexamethasone therapy would be effective in the prevention
      of postextubation stridor and respiratory distress. At study entry, both groups
      had similar weights, postnatal ages, methylxanthine use, ventilator settings,
      blood gas values, and pulmonary function test results (dynamic compliance, total
      respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure,
      minute ventilation, and peak inspiratory and expiratory flow rates). Patients
      underwent blood gas studies, physical examinations, and pulmonary function
      testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to
      24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25
      mg/kg per dose, at baseline, and then every 8 hours for a total of three doses;
      23 infants received saline solution at corresponding times. Eighteen to twenty
      four hours after extubation, total pulmonary resistance increased by 225% from
      baseline in the control group compared with 33% in the dexamethasone group (p <
      0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic
      compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants,
      10 had postextubation stridor compared with 2 of 27 dexamethasone-treated
      patients (p < 0.006). Of the 23 control patients, 4 required reintubation
      compared with none of the treated group (p < 0.05). We conclude that the
      prophylactic use of corticosteroids for the prevention of postextubation stridor
      and respiratory distress is efficacious in low birth weight, high-risk preterm
      infants.

PMID- 1403398
TI  - Effect of dexamethasone therapy on fibronectin and albumin levels in lung
      secretions of infants with bronchopulmonary dysplasia.
AB  - The influence of dexamethasone on levels of total fibronectin (tFn), cellular
      fibronectin (cFn), plasma fibronectin (pFn), and albumin in lung secretions was
      determined in tracheal aspirate samples collected from 45 infants with
      bronchopulmonary dysplasia during a 6-week course of dexamethasone therapy.
      Secretory component for IgA (SC) was used as a reference protein. Thirty-seven
      infants (82%) survived and had their endotracheal tubes successfully removed.
      Corticosteroid therapy was associated with a significant decrease in the cFn/SC
      ratio. There was also a significant decrease in albumin/SC and pFn/SC ratios,
      suggesting decreased capillary permeability with corticosteroid therapy. Four of
      the remaining infants did not improve while receiving corticosteroids and died of
      respiratory failure at 3 to 8 weeks of age. In these "no response" infants,
      tFn/SC, cFn/SC, pFn/SC, and albumin/SC ratios when corticosteroid therapy was
      initiated were threefold to fourfold greater (p < 0.01) than ratios in survivors.
      Another group of four infants initially responded to corticosteroids but
      subsequently died with severe pulmonary cystic degeneration at 4 to 6 months of
      age; in these infants, tracheal aspirate tFn/SC, cFn/SC, and albumin/SC ratios
      were significantly lower than in survivors and remained unchanged during
      corticosteroid therapy. The decrease in the concentrations of plasma fibronectin
      and albumin in tracheal aspirate samples from the survivors suggests that the
      rapid clinical improvement seen in infants with bronchopulmonary dysplasia after
      the initiation of dexamethasone therapy is due in part to improvement in the
      integrity of the alveolar-capillary barrier. In addition, the decrease in the
      aspirate levels of cFn suggests the potential for corticosteroids to limit
      pulmonary fibrosis in the surviving infants. The depressed levels of fibronectin
      observed in the infants with severe cystic lung disease may represent an impaired
      healing response to lung injury.

PMID- 1403399
TI  - Clinical and pharmacologic study of fetal supraventricular tachyarrhythmias.
AB  - The purpose of this study was to evaluate the efficacy of maternal digoxin
      administration in 16 cases of fetal supraventricular tachyarrhythmia diagnosed by
      fetal echocardiography; cardiac anatomy was normal in all cases. The
      retrospective analysis included nine mothers who received digoxin orally in most
      cases, with control of the arrhythmia in two fetuses. The addition of amiodarone
      (five cases) and propranolol (two cases) yielded two successes with amiodarone.
      The therapeutic regimen of digoxin was then modified on the basis of poor
      response to orally administered digoxin. In the prospective study, digoxin was
      administered intravenously to seven mothers according to a standard protocol;
      high doses (1 to 2 mg intravenously) were prescribed for the first 24 hours and
      intravenous digoxin therapy was maintained for at least 5 days, depending on the
      fetal response. Digoxin pharmacokinetic studies of four mothers showed an
      increased plasma clearance and reduced elimination half-life. Digoxin controlled
      the five supraventricular tachycardias (with hydrops in four cases). Maternal
      flecainide therapy restored sinus rhythm in two cases of atrial flutter. Our
      prospective study emphasizes the efficacy and safety for the fetus and the mother
      of intravenously administered digoxin as a first-choice drug in the treatment of
      supraventricular tachyarrhythmias. Flecainide may be a promising second-choice
      drug but requires further clinical investigation. Amiodarone and propranolol seem
      to be ineffective.

PMID- 1403400
TI  - Clinical events in association with timing of intraventricular hemorrhage in
      preterm infants.
AB  - To ascertain whether any routine practices or clinical manipulations in a
      neonatal intensive care unit could induce intraventricular hemorrhage (IVH) in
      preterm infants, we performed ultrasonic monitoring of the germinal layer
      continuously for 48 hours in 33 extremely premature infants with respiratory
      distress. Intraventricular hemorrhage developed in 16 of these infants. In four
      infants the timing of the germinal layer hemorrhage was confirmed with ultrasonic
      monitoring. Three of the four cases were apparently associated with clinical
      events occurring at the moment of IVH: manual ventilation for improvement of
      hypercapnia associated with primary pulmonary hypertension of the newborn;
      correction of hyperkalemia, which was causing an arrhythmia, with administration
      of calcium gluconate and sodium bicarbonate; and administration of surfactant-TA
      to improve respiratory failure caused by pulmonary hemorrhage. In these three
      infants it appeared that one of the basic factors inducing IVH might be an
      increase in blood pressure with or without hypercapnia, causing cerebral
      reperfusion after ischemic damage of the germinal layer.

PMID- 1403401
TI  - Neurologic sequelae in transient nonketotic hyperglycinemia of the neonate.
AB  - We report a neonate with the transient form of nonketotic hyperglycinemia
      manifested by extreme hypotonia, lethargy, apnea, and myoclonic and generalized
      convulsions in early neonatal life. Despite normalization of the biochemical
      values, severe neurologic sequelae were observed. This case suggests that the
      transient form of nonketotic hyperglycinemia sometimes causes severe brain
      damage.

PMID- 1403402
TI  - Two-year results of treatment with depot leuprolide acetate for central
      precocious puberty.
AB  - We report results from 2 years of therapy with the long-acting form of the
      gonadotropin-releasing hormone (GnRH) analog leuprolide acetate, which was
      previously reported in short-term trials to be efficacious in the treatment of
      central precocious puberty. Thirteen girls and two boys, aged 1.9 to 9.7 years,
      who satisfied clinical criteria including GnRH-stimulated luteinizing hormone
      (LH) greater than 10 IU/L (mean radioimmunoassay LH, 29.1 +/- 5.54 IU/L),
      received depot leuprolide, 6 to 15 mg intramuscularly every 4 weeks. Estradiol
      (or testosterone), insulin-like growth factor I, and GnRH-stimulated
      gonadotropins were obtained at baseline, at 2 months, and at 6-month intervals
      with bone age determinations. Pubertal progression ceased in all patients, and
      menses did not occur. Mean increase in height during therapy was 5.77 +/- 2.0
      cm/yr. Predicted adult height increased over baseline by 5.52 +/- 1.16 cm at 18
      months. Mean estradiol values in the girls declined from 3.3 +/- 0.6 to 0.60 +/-
      0.03 ng/dl, with no overlap of baseline and treatment values. The mean basal LH
      value was unchanged by therapy; mean basal and peak LH values for all follow-up
      GnRH stimulation tests were 4.05 +/- 0.57 and 4.95 +/- 0.70 IU/L, respectively.
      Basal and peak follicle-stimulating hormone (FSH) values were suppressed from
      4.10 +/- 0.62 and 10.06 +/- 1.34 IU/L, respectively, to generally undetectable
      levels (< 1). Comparison with untreated control patients suggested that basal LH
      did not completely return to prepubertal levels, whereas FSH levels were
      suppressed below prepubertal levels. Estradiol, FSH, and LH levels reached their
      nadir by 2 months; in contrast, mean serum levels of insulin-like growth factor I
      progressively declined from +0.57 +/- 0.19 SD score to -0.06 +/- 0.22 SD score at
      24 months. Two girls were withdrawn from the study because of reactions at
      injection sites, with apparent sterile abscess formation in one patient. This
      study provides evidence that (1) long-term treatment with depot leuprolide is
      characterized by immediate and sustained laboratory and clinical suppression, (2)
      GnRH-stimulated LH and random FSH and estradiol concentrations are useful
      laboratory measures of efficacy, and (3) the progressive increase in predicted
      adult height is temporally associated with decreased serum levels of insulin-like
      growth factor I and striking deceleration of bone age advancement.

PMID- 1403403
TI  - Stimulation of statural growth by recombinant insulin-like growth factor I in a
      child with growth hormone insensitivity syndrome (Laron type)
AB  - We studied the effects of 9 months of treatment with twice-daily subcutaneous
      injections of insulin-like growth factor I (IGF-I), 120 micrograms/kg per dose,
      in a 9.7-year-old child with growth hormone insensitivity syndrome, in whom short
      term studies had suggested that IGF-I might promote linear growth. Height
      velocity increased from 6.5 cm/yr (+1.7 SD score) to 11.4 cm/yr (+8.8 SD score).
      Serum concentrations of IGF-I increased from pretreatment values of 9 +/- 2
      micrograms/L to a peak of 347 +/- 26 micrograms/L after 2 hours. Serum
      concentrations of IGF-II were unchanged. Basal but not stimulated growth hormone
      concentrations were decreased. During the first 12 days of treatment, serum
      concentrations and the 24-hour urinary excretion of urea nitrogen were decreased
      by 28% and 10%, respectively (p < 0.05), there was a 2.4-fold increase in urinary
      excretion of calcium (p < 0.001), and creatinine clearance and urine volume
      increased by 22% and 55%, respectively (p < 0.02). The changes in serum levels of
      urea nitrogen and in urinary calcium and creatinine clearance were still evident
      at 10 weeks. Fasting and postprandial serum glucose concentrations remained
      normal. We conclude that IGF-I given as twice-daily subcutaneous injections is
      effective in stimulating statural growth without producing the hypoglycemia and
      hyperglycemia observed when IGF-I is infused continuously.

PMID- 1403404
TI  - Use of analgesic agents for invasive medical procedures in pediatric and neonatal
      intensive care units.
AB  - The purpose of this study was to assess the use of analgesic agents for invasive
      medical procedures in pediatric and neonatal intensive care units. The directors
      of 38 pediatric units and 31 neonatal units reported that analgesics were
      infrequently used for intravenous cannulation (10%), suprapubic bladder
      aspiration (8%), urethral catheterization (2%), or venipuncture (2%). Analgesics
      were used significantly more regularly in pediatric than in neonatal intensive
      care units for arterial line placement, bone marrow aspiration, central line
      placement, chest tube insertion, paracentesis, and lumbar puncture.

PMID- 1403405
TI  - Myalgia and elevated creatine kinase activity associated with subcutaneous
      injections of diluent.
AB  - A 16-year-old boy with short stature and mild primary hypothyroidism received
      subcutaneous injections of either recombinant human growth hormone or placebo in
      diluent that contained glycerol and m-cresol as a preservative. While he was
      receiving the study drug, myalgia developed and serum creatine kinase values were
      elevated. Both resolved when injections were stopped and recurred when injections
      of diluent alone were given. The myalgia and elevated creatine kinase activity
      were apparently caused by a component of the diluent.

PMID- 1403407
TI  - Unforgettable patients.

PMID- 1403406
TI  - Back pain and paraplegia in a fifteen-year-old boy.

PMID- 1403408
TI  - Fluid and electrolyte intake in preterm infants.

PMID- 1403409
TI  - Cadaveric renal allograft rejection after treatment with recombinant human growth
      hormone.

PMID- 1403410
TI  - Renal abnormalities associated with Williams syndrome.

PMID- 1403411
TI  - Diagnostic tests for acyl-coenzyme A dehydrogenase deficiency.

PMID- 1403412
TI  - Hemorrhagic shock and encephalopathy: is the gastrointestinal tract the culprit?

PMID- 1403413
TI  - Gerald D. Schmidt 1934-1990: a complex man from a simple beginning.

PMID- 1403414
TI  - Special issue dedicated to Gerald D. Schmidt.

PMID- 1403415
TI  - Gerald D. Schmidt, helminthologist.

PMID- 1403416
TI  - Gerald D. Schmidt from the perspective of a graduate student.

PMID- 1403417
TI  - Energy-linked mitochondrial pyridine nucleotide transhydrogenase of adult
      Hymenolepis diminuta.
AB  - Employing "phosphorylating" submitochondrial particles as the source of pyridine
      nucleotide transhydrogenase, the occurrence of an energy-linked NADH----NADP+
      transhydrogenation in the adult cestode Hymenolepis diminuta was demonstrated.
      The isolated particles displayed rotenone-sensitive NADH utilization and the
      reversible transhydrogenase, with the NADPH----NAD+ transhydrogenation being more
      prominent. Although not inhibiting the NADPH----NAD+ reaction, rotenone, but not
      oligomycin, inhibited the catalysis of NADH----NADP+ transhydrogenation. In the
      presence of rotenone, Mg2+ plus ATP stimulated by more than 3-fold NADH----NADP+
      transhydrogenation. This stimulation was ATP specific and was abolished by EDTA
      or oligomycin. Succinate was essentially without effect on the NADH----NADP+
      reaction. These data demonstrate the occurrence of an energy-linked
      transhydrogenation between NADH and NADP+ with energization resulting from either
      electron transport-dependent NADH oxidation or ATP utilization via the
      phosphorylating mechanism in accord with the preparation of "phosphorylating"
      particles. This is the first demonstration of an energy-linked transhydrogenation
      in the parasitic helminths and apparently in the invertebrates generally.

PMID- 1403418
TI  - Isoenzyme analysis of 35 Toxoplasma gondii isolates and the biological and
      epidemiological implications.
AB  - Isoenzyme analysis was conducted on the tachyzoite stage of 35 Toxoplasma gondii
      isolates. Fifteen enzyme systems were studied after isoelectrofocusing of
      tachyzoite extracts in polyacrylamide or agarose gels. Six enzyme systems showed
      variable electrophoretic patterns: aspartate aminotransferase (EC 2.6.1.1),
      glutathione reductase (EC 1.6.4.2), glucose phosphate isomerase (EC 5.3.1.9),
      amylase (EC 3.2.1.1), acid phosphatase (EC 3.1.3.2), and propionyl esterase.
      Their combination allows the description of 5 zymodemes among the 35 T. gondii
      isolates. Zymodeme 1 involves 6 isolates that are highly pathogenic to mice and
      for which oocysts could not be obtained. Isolates belonging to zymodemes 2, 3,
      and 4 are less pathogenic to mice and produced oocysts. Zymodeme 5 involves only
      1 isolate, which was highly pathogenic to mice.

PMID- 1403419
TI  - A new species of Linstowia (Cestoda: Anoplocephalidae) from marsupials in
      Bolivia.
AB  - A new species of cestode of the genus Linstowia (Cestoda: Anoplocephalidae) is
      described from marsupials of the genera Thylamys and Monodelphis. The new species
      (Linstowia schmidti) differs from Linstowia iheringi Zschokke, 1904, in having a
      much smaller strobila and reduced number of proglottids, and in the distribution
      of the eggs in gravid proglottids. In Bolivia, cestodes of the genus Linstowia
      appear to have a restricted geographic distribution, occurring in marsupials only
      in southeastern Bolivia near the western margin of the Chaco. This host-parasite
      association may represent an ecological-historical relict.

PMID- 1403420
TI  - Tikusnema javaense n. gen., n. sp. (Nematoda: Acuarioidea) and other nematodes
      from Rattus argentiventer collected in west Java, Indonesia.
AB  - Nematodes collected from the ricefield rat, Rattus argentiventer (Rodentia:
      Muridae), in Pusakanagara and Sukamandi, West Java, Indonesia, are reported.
      Tikusnema javaense n. gen., n. sp. (Nematoda:Acuariidae:Seuratiinae) is described
      from the small intestine. This new genus is distinguished readily from other
      genera of the subfamily Seuratiinae in having 4 strongly protruded cuticular
      leaves in the posterior cephalic portion and in having a pair of prominent
      cuticular ornamentations posterior to deirids. Besides T. javaense, Eucoleus
      bacillatus, Strongyloides ratti, Nippostrongylus brasiliensis, Syphacia muris,
      and Physaloptera sp. were detected.

PMID- 1403421
TI  - Two new coccidian parasites from the slate-colored grosbeak (Pitylus grossus) of
      South America.
AB  - In July and August 1990, fecal samples from 2 slate-colored grosbeaks were
      collected from the rain forest of Ecuador. Upon examination, 2 new species of
      coccidia were discovered. Oocysts of Isospora pityli n. sp. are spheroid or
      subspheroid, 20.1 x 18.8 (20-20.5 x 17-20) microns, with a shape index of 1.07
      (1.0-1.18) but lacking a micropyle, oocyst residuum, and polar granules.
      Sporocysts are ovoid, 14.7 x 9.4 (12-17 x 8-11) microns, with small nipplelike
      Stieda bodies, no substieda bodies, and residua composed of an amorphous cluster
      of coarse, nonuniform granules. Sporozoites each possess a large refractile body
      at 1 end and appear to be enclosed in a thin membrane within the sporocyst along
      with the residuum. Oocysts of L. formarum n. sp. are spheroid or subspheroid,
      24.6 x 23.5 (21-27 x 20-25) microns, with a shape index of 1.05 (1.0-1.09) but
      with no micropyle, oocyst residuum, or polar granules. Sporocysts are ovoid, 15.7
      x 11.3 (14-17 x 10-13) microns, with small, nipplelike Stieda bodies and large
      triangular or conical-shaped substieda bodies with irregular lower edges.
      Sporozoites each possess an oblong refractile body at 1 end and appear packed
      together randomly and enclosed in a membrane along with a spheroid residuum
      composed of fine, uniform granules.

PMID- 1403422
TI  - Onchocerciasis in Minnesota cattle.
AB  - Umbilical hides from 536 dairy cattle in Minnesota were tested for the
      microfilarial stage of Onchocerca species to determine the distribution of
      onchocerciasis in the state. The infection was widespread as microfilariae were
      obtained from 214 (40%) of the animals, representing nearly all areas of the
      state. Adult Onchocerca parasites were collected primarily from nodules
      associated with tibial bones but also were found to a lesser extent within the
      gastrosplenic ligament. Specific identity of these organisms is unclear as they
      exhibit certain morphological features previously described as being
      characteristic of either Onchocerca gutturosa, Onchocerca lienalis, or Onchocerca
      stilesi.

PMID- 1403423
TI  - A nucleic acid-based test for detection of Fasciola hepatica.
AB  - The use of nucleic acid techniques in the diagnosis of parasitic infection has
      become increasingly widespread. An oligonucleotide probe derived from a rRNA
      sequence was developed for the detection of Fasciola hepatica in its intermediate
      snail host Pseudosuccinea columella. Total RNA obtained from whole adult liver
      flukes was used in a polymerase chain reaction to isolate and amplify a region of
      approximately 650 base pairs in the small subunit rRNA. This portion of the
      ribosomal cDNA, which contains highly conserved regions as well as variable
      regions, was subcloned and sequenced. In comparison to known small subunit rRNA
      sequences, a sequence unique to F. hepatica was identified and an oligonucleotide
      probe (CS4) for detection of F. hepatica was developed. A northern blot analysis
      using CS4 successfully identified small subunit rRNA from F. hepatica. Slot-blot
      analysis determined that RNA derived from 5 miracidia can be detected with CS4.
      Moreover, a slot blot utilizing CS4 distinguished RNA derived from snails
      infected with F. hepatica from RNA of uninfected snails.

PMID- 1403424
TI  - Minimizing ELISA background in the diagnosis of swine trichinellosis.
AB  - After confirming that long-term serum storage (frozen at -20 C for greater than 3
      mo) causes optical density to drift upward, several modifications of an enzyme
      linked immunosorbent assay (ELISA) protocol were evaluated to identify a protocol
      that would reduce background in porcine sera tested for trichinellosis.
      Modifications evaluated included blocking the antigen-coated ELISA plate with
      sample diluent containing 10% bovine serum albumin (BSA) or 10% nonfat milk
      powder (bovine lacto transfer optimizer or BLOTTO), diluting sera in sample
      diluent containing 10% BSA or 10% BLOTTO, and preincubating samples in sample
      diluent containing 10% BSA or 10% BLOTTO. Overnight preincubation (approximately
      12 hr at 2 C) of fresh sera diluted (1:10) in sample diluent containing 10%
      BLOTTO significantly reduced background and improved the detection of
      experimentally infected pigs by enhancing positive-negative discrimination. When
      testing stored sera, the modified protocol effectively reduced the effect of
      storage and the kit revealed specificity of 98.4%; there was no loss in
      sensitivity. The effect of long-term storage at -20 C must therefore be
      considered when testing swine sera for trichinellosis by ELISA and possibly also
      when conducting other immunoglobulin assays. The modification described here may
      prove useful if there is no alternative to using serum stored for greater than 3
      mo at -20 C.

PMID- 1403425
TI  - Host-parasite relationships of longnose dace, Rhinichthys cataractae, from the
      Ford River, Michigan.
AB  - A total of 1,115 longnose dace, Rhinichthys cataractae (family Cyprinidae), were
      examined for parasites from May 1983 through October 1986 from 3 localities in
      the Ford River in Michigan's Upper Peninsula. Thirteen parasite species (1
      Monogenea, 2 Digenea, 2 Cestoda, 4 Nematoda, 1 Acanthocephala, 3 Protozoa)
      infected dace. The parasite faunas of dace, taxonomically and in species number,
      were similar between localities. Posthodiplostomum minimum minimum, Neascus sp.,
      and Rhabdochona canadensis were the most common helminths infecting dace from
      each locality. The first 2 species did not exhibit consistent seasonal infection
      patterns between years, whereas the prevalence and mean intensity of R.
      canadensis in dace from the downriver locality were higher in summer 1983, 1984,
      and 1985. The intensity of infection of each of these helminth species
      significantly increased with host length. The prevalences and mean intensities of
      P. m. minimum, Neascus sp., and R. canadensis as well as the helminth
      infracommunity diversity were highest in dace from the upriver locality. The
      major factors that influenced parasite intensity were environmental factors that
      occurred when and where a fish began its life, the sequence of events that
      occurred in each habitat the fish encountered during its life, and the length of
      exposure (age of fish). Dace have isolationist helminth infracommunities arising
      from factors including ectothermy, a simple enteric system, restricted vagility,
      and being gape-limited. Allogenic helminths with indirect life cycles predominate
      in the depauperate helminth fauna of dace.

PMID- 1403426
TI  - Reduced splash dispersal of bovine parasitic nematodes from cow pats by the dung
      beetle Diastellopalpus quinquedens.
AB  - From a thoroughly mixed portion of cattle feces with Cooperia sp. eggs, 1-kg
      artificial pats were placed in 6 buckets containing 6 kg of soil each. Ten dung
      beetles, Diastellopalpus quinquedens, were added to each of 3 buckets. The
      remaining 3 buckets served as controls without beetles. When infective parasite
      larvae (L3) had developed in the cow pats indoors, the following procedure was
      followed. During occasions of rainfall each bucket was placed outdoors in the
      center of a wider and higher container. When the rain stopped all buckets were
      brought indoors, and infective larvae spread by splash droplets during the rain
      were collected in the containers and counted. After 33 days, the remaining dung
      on the soil surface in buckets with dung beetles constituted only 38% of that in
      the controls. Moreover, the number of L3 in feces left on the soil surface in the
      buckets with beetles was reduced by 88%, presumably due to beetle activity. This
      may explain the 70-90% reduction in splash dispersal of L3 of Cooperia sp. from
      cow pats attacked by beetles. The dung-burying activity of the beetles did not
      result in increased numbers of L3 in the soil under the cow pats, suggesting that
      many of the parasites in buried feces were destroyed.

PMID- 1403427
TI  - Chemotactic response of macrophages to Acanthamoeba castellanii antigen and
      antibody-dependent macrophage-mediated killing of the parasite.
AB  - The chemotactic potential of antigens of Acanthamoeba castellanii for macrophages
      and the ability of naive and immune rat peritoneal macrophages to kill A.
      castellanii in vitro were assessed. The amoebolytic capacity of immune rat serum
      and complement was also examined. No parasite was killed in the presence of heat
      inactivated naive rat serum. Low numbers of parasites were lysed in the presence
      of heat-inactivated immune rat serum, whereas significantly greater numbers of
      parasites were lysed in the presence of nonheat-inactivated naive and immune rat
      serum. Macrophages from naive rats were capable of lysing some parasites.
      However, the amoebolytic capability of these cells was significantly increased in
      the presence of serum from immune rats. Regardless of the source of serum used,
      macrophages from immune rats demonstrated about twice the amoebolytic proficiency
      of cells from naive rats. Macrophages from naive rats showed their highest
      capacity for lysing amoebae when incubated in the presence of gamma interferon
      and immune rat serum. The greatest overall proficiency in lysing parasites was
      displayed by cells from immune rats incubated with A. castellanii in the presence
      of gamma interferon and nonheat-inactivated serum from immune rats.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 1403428
TI  - Incorporation of [3H]hypoxanthine by short-term cultured Theileria sergenti and
      its inhibition by drugs.
AB  - Red blood cells parasitized with Theileria sergenti were cultured in vitro for a
      short period in microplate wells. Addition of [3H]hypoxanthine to cultures
      enabled us to titrate the intraerythrocytic parasite growth because a significant
      amount of [3H]hypoxanthine was incorporated into the parasitized red blood cells
      (PRBC) in proportion to the number of PRBC. The incorporation of [3H]hypoxanthine
      was almost completed in an early phase of incubation. Bovine peripheral blood
      leukocytes incubated with lysate of PRBC did not incorporate [3H]hypoxanthine,
      indicating that contaminating leukocytes were not involved in the incorporation
      in the PRBC culture. The incorporation of [3H]hypoxanthine was decreased markedly
      by the addition of certain anti-parasitic drugs such as chloroquine, quinine, and
      pyrimethamine. This inhibition test was performed quantitatively with high
      sensitivity. Based on these results, this short-term culture seemed to be useful
      for drug screening or studying the mechanisms of theilerial infection. However,
      anti-T. sergenti antibodies failed to inhibit the [3H]hypoxanthine incorporation.

PMID- 1403429
TI  - Developmental biology and migration of Strongyloides ratti in the rat.
AB  - Most recent authors suggest that larvae of the threadworm, Strongyloides ratti,
      migrate from a cutaneous infection site to the small intestine via the naso
      frontal region of the head. However, the proportion of larvae that successfully
      reach the intestine having followed this pathway had not been determined. Using
      compartmental analysis we have obtained a comprehensive quantitative description
      of larval migration during a primary infection of rats with S. ratti. Mean
      residence times in organs through which larvae migrate were calculated and the
      proportion of the larvae arriving in the small intestine via the head was
      estimated as 0.5-0.86, depending on the mathematical model used to generate the
      estimate. With 50% or more of successful larvae using this pathway it is now
      reasonable to recognize the "head route" as an important migratory pathway for
      larvae traveling to their intestinal predilection site. During the first 12 hr in
      the host, larvae were difficult to recover from the skin and subjacent muscles of
      the infection site. Apparently, upon invading a host, many larvae enter a
      quiescent phase during which Baermannization, an active recovery technique, fails
      to recover them. Infections were short-lived, with the daily finite mortality
      rate for adult worms attaining 50-80% on day 16 of infection.

PMID- 1403430
TI  - Effect of cobalt-60 irradiation on the infectivity of Paragonimus westermani
      metacercariae.
AB  - A study was made to observe the effect of cobalt-60 irradiation on the viability
      of Paragonimus westermani metacercariae in Sinopotamon chekiangense crabs. The
      crabs were collected in mountain regions of the Zhejiang Province of China in
      which paragonimiasis is endemic. Adult cats and albino mice were infected with
      metacercariae irradiated at different doses. Dissection of the host animals was
      conducted 90 or 30 days, respectively, after infection for recovery of lung
      flukes. Anti-metacercariae antibody in infected mice was measured by enzyme
      linked immunosorbent assay (ELISA). Results showed that metacercariae were unable
      to grow into adult worms in cats after exposure to gamma irradiation at a dose of
      0.10 kGray. However, a small number of metacercariae exposed to a dose of 2.0
      kGray excysted and survived in 1 mouse for 30 days. No worm was recovered from
      mice when the metacercariae were irradiated at a dose of 2.5 kGray. Seropositive
      results by ELISA were obtained when the mice were infected with metacercariae
      irradiated at doses ranging from 2.0 to 3.5 kGray.

PMID- 1403431
TI  - Characterization of the intracellular melanization response in Anopheles
      quadrimaculatus against subperiodic Brugia malayi larvae.
AB  - Intracellular melanization, a defense or an immune response in the thoracic
      muscle cells, was investigated in a refractory strain of Anopheles
      quadrimaculatus infected with larvae of Brugia malayi. In mosquitoes fed on B.
      malayi-infected jirds, intracellular melanization against first-stage larvae (L1)
      was better expressed when fewer than 40 microfilariae reached the thoracic muscle
      cells than when more than 40 microfilariae reached the thoracic muscle cells.
      This result suggests that when large numbers of microfilariae invade the thoracic
      muscle cells, the immune response of the mosquito may become overloaded.
      Intracellular melanization response against L1 in the thoracic muscle cells also
      showed a significant decrease in older females (14-16-day-old) as compared to the
      younger ones (4-9-day-old). A comparison is made between intracellular and
      extracellular responses of mosquitoes to filarial larvae. It is significant that
      in both cases high rate of infection can reduce both the number and percentage of
      larvae melanized.

PMID- 1403432
TI  - Effects of eimerian (Apicomplexa: Eimeriidae) infections on nutrient assimilation
      in the Wyoming ground squirrel.
AB  - Effects of infection with mixed species of Eimeria (E. callospermophili, E.
      morainensis, and E. beecheyi) on the digestive physiology of Wyoming ground
      squirrels (Spermophilus elegans) are described. Infected and uninfected squirrels
      were administered arginine and methionine in saturated glucose solution. Blood
      was drawn at time 0 and 30 min postadministration. Significant differences were
      not found between infected and uninfected squirrels in plasma glucose, arginine,
      or methionine assimilation. In a second experiment, infected and uninfected
      squirrels were fed a food slurry of known caloric value. All feces were collected
      for 24 hr postfeeding. Differences were not detected in fecal caloric content or
      digestive efficiency. These results in conjunction with results reported in the
      literature suggest a reassessment of the "parasitic" nature of these squirrel
      symbionts. We propose that associations of some Eimeria species and hosts that
      evolve under natural conditions are examples of parasite-host interactions that
      often evolve toward commensalism.

PMID- 1403434
TI  - Response to ivermectin treatment of parasitic stages of Haemonchus contortus
      resistant or susceptible to ivermectin.
AB  - Two groups of 33 helminth-naive lambs were infected with 5,000 L3 of an
      ivermectin-resistant or -susceptible strain of Haemonchus contortus (groups R and
      S). On days 6, 10, 16, and 21 postinfection, 5 animals from each group were
      chosen at random and orally treated with 0.2 mg/kg of ivermectin. On each
      occasion, 2 randomly selected lambs from each group were also killed to determine
      the number and stage of development of the worms present at the time of
      treatment. These necropsies revealed that by day 6 early and late fourth-stage
      larvae were present, whereas on day 10 the early fifth stage had been reached; by
      days 16 and 21 all worms had reached the adult stage. Necropsies on day 28
      postinfection revealed that although animals treated at day 6 had 26.3% fewer
      worms than the controls, there was no significant difference (P greater than
      0.05) between worm burdens from any of the animals infected with the R strain and
      treated at different times after infection when compared with the untreated
      controls. With ivermectin significant reductions were obtained in the worm
      burdens of the animals infected with the susceptible strain; these were reduced
      by 96% when treatment was given on day 6 against fourth-stage larvae and 98.9%
      when the drug was given on day 21 against adult stages. From these results it is
      clear that resistance to ivermectin in this strain of H. contortus is present as
      early as the fourth larval stage.

PMID- 1403433
TI  - Identification and partial purification of a lectin on the surface of the
      sporozoite of Cryptosporidium parvum.
AB  - A human-derived isolate of Cryptosporidium parvum from a symptomatic patient with
      the acquired immunodeficiency syndrome was expanded in vivo by infecting a
      neonatal calf with 10(8) oocysts. Sporozoites were isolated from 4 x 10(10)
      oocysts harvested from this single infection, and the characteristics of mixed
      hemagglutination (HA) with rabbit erythrocytes were determined. Sporozoite HA was
      inhibited by bovine submaxillary mucin (BSM), hog gastric mucin, and orosomucoid,
      but not by simple sugars, including sialic acid. Carbohydrate-inhibitable HA
      (lectin) activity increased with sporozoite lysis and was associated with the
      sporozoite membrane fractions. The ability of intact sporozoites to form rosettes
      around erythrocytes indicates that the HA (lectin) is, at least in part, present
      on the parasite surface. Hemagglutination (lectin) activity was partially
      purified from sporozoite lysates by affinity chromatography with BSM coupled to
      Sepharose-4B. Best elution was obtained with ethylene glycol and NaCl, which
      resulted in enrichment of 6 bands compared to the crude starting lysate (Mr = 60,
      24, 22, 20, and 15 kDa and a 40-kDa doublet). Our results indicate that an HA
      (lectin) activity is present on the surface of intact sporozoites where it could
      play a role in cell-to-cell interactions with eukaryotic targets.

PMID- 1403435
TI  - Metazoan parasites of the mountain beaver, Aplodontia rufa (Rodentia:
      Aplodontidae), from Washington and Oregon, with a checklist of parasites.
AB  - Four species of fleas, 2 species of mites, and the cysticerci of Taenia
      tenuicollis were collected from mountain beavers, Aplodontia rufa, collected in
      Washington and Oregon. A summary of the metazoan parasites reported from A. rufa
      is included.

PMID- 1403436
TI  - Experimental infections of Eimeria alpacae and Eimeria punoensis in llamas (Lama
      glama).
AB  - Four llamas (Lama glama) ranging in age from 1.5 yr to 7 yr each were inoculated
      orally with 10,000 (n = 2) or 50,000 (n = 2) sporulated oocysts of Eimeria
      alpacae (25%) and Eimeria punoensis (75%). The prepatent period for E. aplacae
      was 16-18 days, and it was 10 days for E. punoensis. Patent periods for E.
      alpacae and E. punoensis were approximately 9 days and 24 days, respectively.
      Although large numbers of oocysts were present in feces, no clinical sign of
      coccidiosis was observed. Based on ths experiment, E. alpacae and E. punoensis at
      the numbers given are not likely pathogenic in healthy llamas older than 1 yr.

PMID- 1403437
TI  - Equine protozoal myelitis in Panamanian horses and isolation of Sarcocystis
      neurona.
AB  - Schizonts of Sarcocystis neurona were identified microscopically in hematoxylin
      eosin-stained spinal cord sections from 2 native Panamanian horses that exhibited
      clinical signs of equine protozoal myelitis (EPM). Spinal cord homogenate from a
      third Panamanian horse with EPM was inoculated onto monolayers of cultured bovine
      monocytes (M617). Intracytoplasmic schizonts containing merozoites arranged in
      rosette forms surrounding a central residual body first were observed 13 wk
      postinoculation. Parasites divided by endopolygeny and lacked rhoptries.
      Schizonts from each horse reacted with Sarcocystis cruzi antiserum in an
      immunohistochemical test.

PMID- 1403438
TI  - Infections of Gyrodactylus bullatarudis and Gyrodactylus turnbulli on guppies
      (Poecilia reticulata) in Trinidad.
AB  - Gyrodactylus bullatarudis Turnbull, 1956, and Gyrodactylus turnbulli Harris,
      1986, are recorded from guppies (Poecilia reticulata) from the northern mountains
      of Trinidad. Mixed infections of the 2 species were found at 9 localities.
      Gyrodactylus turnbulli had a predominantly posterior distribution on the fishes,
      whereas G. bullatarudis was more anteriorly distributed. This is the first record
      of these species from guppies collected from within their original range.

PMID- 1403439
TI  - A possible genetic factor influencing protection from infection with Ascaris
      lumbricoides in Nigerian children.
AB  - An epidemiological study of Ascaris lumbricoides infections was carried out in
      primary school children aged 5-16 yr from Ile-Ife, Nigeria. Intensity of
      infection was assessed directly by means of counting worms passed during a 48-hr
      period after chemotherapy. Reinfection patterns of A. lumbricoides were assessed
      at 2 6-mo intervals and statistical evidence of predisposition to infection
      status was obtained. An investigation of 3 groups of children who were judged to
      be predisposed not to be infected, to be lightly infected, and to be heavily
      infected was undertaken. Assignment to the groups was based upon the mean worm
      burden plus 1 SD above the mean, measured at 2 6-mo intervals. The distribution
      of class I human leucocyte antigens among the 3 groups of children was described.
      None of the children who were predisposed to remain uninfected was found to
      possess the A30/31 antigens in contrast to those children who remained infected.

PMID- 1403440
TI  - Secretion of metalloproteases by living infective larvae of Necator americanus.
AB  - Fresh living third-stage larvae of Necator americanus released a significant
      amount of label within 2 hr of their incubation on 125I-labeled gelatin-coated
      polystyrene plastic plates. This protease activity was primarily susceptible to o
      phenanthroline, which identifies the activity as predominantly metalloprotease.

PMID- 1403441
TI  - Twinning in metacestodes of Taenia solium.
AB  - Two cysticerci containing 2 scolices were found among several thousand Taenia
      solium metacestodes dissected from swine. Microscopic study of tissue sections
      revealed that both worms were equally well developed in 1 bladder worm, whereas 1
      member of the other pair was incompletely formed.

PMID- 1403442
TI  - The U.S. National Parasite Collection--a century of service.
AB  - The U.S. National Parasite Collection will complete its first century of service
      to the field of animal parasitology in 1992. A brief history of the collection
      and a description of current policies on deposit and loan of specimens are
      provided. The collection, started in 1892 by Charles Wardell Stiles and Albert
      Hassall, now includes several constituent collections: The USNM Helminthological
      Collection, The USDA Parasite Collection, The Hoffman-Bangham Collection of
      Parasites of Freshwater Fish, and The Southeastern Cooperative Wildlife Diseases
      Study Collection of Parasites of White-tailed Deer. Major personal collections
      have been donated by F. W. Douvres, J. H. Fischthal, A. O. Foster, A. Goldberg,
      E. P. Hoberg, R. Honess, R. A. Knight, D. C. Kritsky, R. E. Kuntz, G. L. LaRue,
      D. R. Lincicome, E. Linton, G. A. MacCallum, J. H. Sandground, L. Schultz, and H.
      J. Van Cleave. In addition to Stiles and Hassall, the collection has been curated
      by B. H. Ransom, M. C. Hall, A. McIntosh, W. W. Becklund, M. B. Chitwood, and the
      authors of this report. Other USDA researchers closely associated with the
      collection over the years include B. G. Chitwood, E. B. Cram, G. Dikmans, J. T.
      Lucker, E. W. Price, and E. E. Wehr. The collection includes about 90,000 lots of
      specimens, mostly helminths, but also significant numbers of ticks, mites,
      protozoans, and other miscellaneous parasites. Annually about 600-1,000 lots are
      accessioned and 300-400 lots are loaned to researchers around the world.

PMID- 1403443
TI  - 1 beta-hydroxylated bile acids in the urine of healthy neonates.
AB  - In order to clarify the metabolism of bile acids in neonates, 1 beta-hydroxylated
      bile acids in the urine of healthy newborns were examined by gas chromatography
      mass spectrometry. The results showed that the percentage of total 1 beta
      hydroxylated bile acids, 3 beta, 12 alpha-dihydroxy-5-cholenoic acid and
      hyocholic acid in neonates was significantly higher than in older children. The
      ratio of 1 beta-hydroxylated bile acids to their comparable primary bile acids
      was also higher in neonates than in older children. These results suggest that 1
      beta- and 6 alpha-hydroxylation of bile acids are the predominant pathways of
      bile acid metabolism in neonates.

PMID- 1403444
TI  - Colonic hematoma after blunt abdominal trauma.

PMID- 1403445
TI  - Abnormal gut blood flow velocities in neonates at risk of necrotising
      enterocolitis.
AB  - Duplex pulsed Doppler ultrasound was used to determine blood flow velocities in
      the coeliac axis and superior mesenteric artery in three groups of neonates: a
      group at high risk of developing necrotising enterocolitis (n = 27) and two
      control groups, i.e., a nonasphyxiated, appropriately grown group of preterm
      infants (n = 18) and a group of nonasphyxiated term infants (n = 14). Subjects
      were studied on the first, second, and fourth days of life. The median peak
      systolic velocities in the superior mesenteric artery were between 20 and 51%
      lower in the at-risk group than in the term control group on all 3 days of
      measurement (p less than 0.05-p less than 0.002). The ratio of peak systolic
      velocity in the coeliac axis to that in superior mesenteric artery, an index of
      relative downstream vascular resistance in the superior mesenteric artery, was 42
      65% greater in the at-risk group compared with the other two groups on days 1 and
      2 (p less than 0.05-p less than 0.001) and significantly greater than the term
      group on day 4 (73%, p less than 0.002). These data demonstrate that neonates at
      risk of developing necrotising enterocolitis have abnormal gut blood flow
      velocities. Furthermore, they provide evidence that an alteration in the
      splanchnic circulation may be an important factor in the final common pathway
      that links diverse risk factors for necrotising enterocolitis with clinical
      disease.

PMID- 1403447
TI  - Solubility and digestibility of milk proteins in infant formulas exposed to
      different heat treatments.
AB  - There are presently several fundamentally different technologies to produce
      infant formulas (IF), such as sterilization, spray-drying, and treatment at
      ultrahigh temperature (UHT). The effects of heat treatment on milk proteins in IF
      were analyzed by column chromatography, gel electrophoresis, and Kjeldahl
      analysis, revealing strong protein-protein and protein-lipid interactions in
      processed milk. These interactions were more pronounced in conventionally (in
      can) sterilized than in spray-dried (powdered) and UHT products confirming their
      temperature dependency. Analysis of raw materials, intermediate and end products
      of IF processing revealed that after homogenization the first indications of
      protein denaturation occurred, but that in-can sterilization as the final heat
      treatment caused irreversible denaturation of proteins and strong protein-lipid
      interactions. Lowering of the pH to 4-5, which is physiological for the stomach
      of young infants, enhanced the interactions. Support for an impairment of protein
      digestibility was given by in vitro analysis of protein digestibility,
      demonstrating significantly lower digestibility of in-can sterilized IF compared
      to their spray-dried and UHT counterparts. To investigate the effect of heat
      treatment on chemical reactions, i.e., occurrence of Maillard products, we showed
      by a fluorimetric assay that the amount of "available" lysine is lower in
      sterilized than in powdered IF. Our findings suggest that a more differentiated
      view regarding the protein quality of IF is needed.

PMID- 1403446
TI  - Milk-stimulated PGE2 production by isolated gastric cells: a possible role in the
      inhibition of histamine-induced acid secretion.
AB  - The effects of a milk diet on gastric acid secretion of rats fed raw bovine milk
      for 4 days were examined using dispersed gastric cells. Parietal cell acid
      secretion was estimated by the accumulation of 14C-aminopyrine (AP), an index of
      secretory function. Basal AP accumulation was significantly increased (60%) by
      the milk diet. There was a marked upward shift in the dose-response curve of
      histamine (HA; 10(-8) to 10(-3) M) in milk-fed rats, indicating enhanced
      sensitivity of parietal cell-H2 receptor to exogenous HA. In contrast, the dose
      dependent inhibition of HA-induced AP accumulation by prostaglandin (PG) E2 was
      significantly reduced, indicating that the parietal cells of milk-fed rats were
      less sensitive to exogenous PGE2. The PGE2 content of bovine milk was low (less
      than 20 pg/ml), but the production of endogenous PGE2 by the gastric cells was
      dramatically increased by the milk diet and exhibited maximal control production
      rate in the presence of 10 microM arachidonic acid. The increased responsiveness
      to histamine and the decreased responsiveness to PGE2 indicated that the milk
      diet induced low histamine and high PGE2 availability in the vicinity of the
      parietal cell basolateral membrane. This regulation, which involves stimulation
      of PGE2 production in the gastric mucosa, may underly the inhibition of acid
      secretion observed in vivo in chronically milk-fed adult rats.

PMID- 1403448
TI  - Comparison of two preterm formulas with or without addition of medium-chain
      triglycerides (MCTs). I: Effects on nitrogen and fat balance and body composition
      changes.
AB  - Medium-chain triglycerides (MCTs) are included in the fat blend of several
      preterm formulas because of their complete absorption and rapid oxidation. The
      effects of two different fat blend compositions on nitrogen and fat balances and
      macronutrient oxidation were investigated in 28 healthy very-low-birth weight
      infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT
      blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed
      to resemble human milk more, containing 6% MCTs (LCT group). There were no
      differences in nitrogen absorption or in excretion. Median nitrogen retention was
      74% (MCT) vs. 71% (LCT) of intake. Fat absorption was higher (p less than 0.05)
      in the MCT group (88%) vs. 79% in the LCT group (median values). MCTs did not
      stimulate fat oxidation as measured by indirect calorimetry, so fat deposition
      was also higher on the MCT formula. As weight gain was not different between
      groups, the percentage of weight gain consisting of fat accretion was
      significantly (p less than 0.005) higher with the MCT formula (24% vs. 21%). On
      the other hand, there was no increase in percent protein accretion (both 15% of
      weight gain). We conclude that the existence of a slightly lower fat absorption
      in the healthy growing neonate fed a LCT formula compared with a MCT formula does
      not impair growth or nitrogen retention, but merely induces a slight decrease in
      the high relative fat accretion encountered in the preterm neonate.

PMID- 1403450
TI  - Significance of intestinal food protein transport.

PMID- 1403449
TI  - Comparison of two preterm formulas with or without addition of medium-chain
      triglycerides (MCTs). II: Effects on mineral balance.
AB  - Medium-chain triglycerides (MCTs) are included in the fat blend of several
      preterm formulas because of their complete absorption and rapid oxidation. The
      effects of two different fat blend compositions on calcium (Ca), phosphorus (P),
      and magnesium (Mg) balances and plasma levels and on plasma levels of parathyroid
      hormone (PTH), alkaline phosphatase (AP), and 1,25-dihydroxyvitamin D [1,25
      (OH)2D] were investigated in 28 healthy very-low-birth weight infants at 4 weeks
      of age. A preterm formula with a traditional corn oil/MCT blend containing 38%
      MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk
      more, containing 6% MCTs (LCT group). There was a higher absorption of Ca in the
      MCT group (73% vs. 60%. p less than 0.005), and an equal absorption of P (both
      92%). The excretion of Ca correlated with the excretion of fat (p less than
      0.00005). The LCT group showed a higher median PTH level (MCT: 2.1 pmol/L, LCT:
      4.7 pmol/L, p less than 0.01) and a higher urinary P excretion (p less than
      0.001). Mg absorption was also lower with LCT, but retention of Mg exceeded
      intrauterine values in both groups. Mineral plasma levels were in the normal
      range in both groups. AP was not different between groups and in the upper part
      of the reference range, whereas 1,25-(OH)2D levels were above the normal range
      and also not different between groups. We conclude that with the LCT formula, Ca
      absorption is slightly lower than with the MCT formula, whereas P absorption is
      unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 1403452
TI  - Doppler assessment of human neonatal gut blood flow velocities: postnatal
      adaptation and response to feeds.
AB  - Duplex pulsed Doppler ultrasound was used to study changes in gut blood flow
      velocities during the first week of life in a group of 14 term babies. There was
      a significant increase in fasting peak systolic velocity in the superior
      mesenteric artery between days 1 and 2 with a further upward trend until day 5;
      no such changes were seen in the coeliac axis. Fasting velocities were 20% lower
      in breast-fed babies than bottle-fed babies. Following feeds, there was a
      significant increase in velocity in the superior mesenteric artery that was 35%
      greater in the bottle-fed than breast-fed babies. Changes in the coeliac axis
      were qualitatively similar but substantially smaller. The peak velocity in both
      vessels occurred 50 min after a feed. We conclude that Doppler ultrasound can be
      readily used to measure gut blood flow velocities in the human newborn. It
      provides a noninvasive technique for investigating adaptive postnatal changes in
      the splanchnic circulation, and, in particular, the response to feeds.

PMID- 1403451
TI  - Basal and meal-stimulated pepsinogen secretion in preterm infants: a longitudinal
      study.
AB  - In order to establish longitudinal normal values for basal and meal-stimulated
      pepsinogen secretory function in preterm infants, we studied 44 preterm infants
      with gestational ages of 28-36 weeks during the period of nasogastric tube
      feeding. Three age groups were evaluated: gestational ages of 28-30, 31-33, and
      34-36 weeks. Basal pepsinogen did not change with postnatal age in any of the
      groups. Significant meal-stimulated pepsinogen secretion appeared during the
      third postnatal week in infants of 28-30 weeks of gestation. In the groups of
      infants of 31-33 and 34-36 weeks of gestation, significant meal-stimulated
      pepsinogen secretion was apparent in the first postnatal week. This study
      suggests that maturation of pepsinogen secretion appears at 31 weeks of
      gestation, independent of early feeding.

PMID- 1403453
TI  - Esophagitis of likely traumatic origin in newborns.
AB  - We describe 17 full-term newborns presenting with vague symptoms related to the
      upper gastrointestinal tract (anorexia, poor feeding, retching, regurgitation,
      and incessant crying) during their stay in the maternity unit. After an
      esophagogastroduodenoscopy performed between days 2 and 5 of life, the babies
      could clearly be divided into two groups. Twelve babies (group 1) had an
      extremely severe esophagitis (circular ulcerations), without gastroduodenitis. In
      the remaining five babies (group 2), the upper gastrointestinal tract was
      unaffected. Allergic, infectious, metabolic, and toxic etiologies were excluded.
      Esophageal pH monitoring data were within normal ranges in all. All babies of
      group 1 were treated as follows: prone anti-Trendelenburg position, cisapride,
      and cimetidine syrup. Symptoms and lesions disappeared within 48-72 h.
      Reendoscopy after 72 h showed an almost normal esophagus with greatly improved
      histology. These observations highlight four points of interest: (a) the
      existence of an extremely severe ulcerative esophagitis in apparently healthy
      newborns, (b) the very rapid clinical and histological recovery, (c) the
      difficulties in predicting esophagitis on clinical grounds, and (d) the
      mysterious origin despite thorough assessment. The distribution of the lesions
      (more severe in the upper esophagus), the early onset (almost at birth), the very
      rapid healing, and the absence of gastric and duodenal lesions are in favor of a
      possible "traumatic" origin (pharyngeal, esophageal, and gastric suction at
      birth). Finally, because the condition described is transient, questions arise
      regarding the necessity of treatment, and we currently do not recommend
      overtreating newborns presenting with similar symptoms and/or endoscopic
      findings.

PMID- 1403454
TI  - Midazolam as a sedative in esophageal manometry: a study of the effect on
      esophageal motility.
AB  - Midazolam 0.5 mg/kg was given intravenously as a sedative to 19 infants and
      children undergoing esophageal manometry after oral choral hydrate treatment. The
      lower esophageal sphincter pressure and motility were measured by manometry
      before and after midazolam injection. Midazolam did not change the lower
      esophageal sphincter pressure, blood pressure and respiratory rate of the
      subjects (p greater than 0.18), and the motility patterns. However, the mean
      heart rate increased by 5 beats/min after midazolam injection (p less than 0.05).
      One infant developed transient apnea, reversed promptly by intravenous
      flumazenil. Sedation occurred within 1 min after intravenous injection of the
      drug. No other side effects were noted. Midazolam is a relatively safe and
      effective sedative for accurate lower esophageal sphincter pressure measurement
      and esophageal manometry when a mild sedative such as choral hydrate does not
      work.

PMID- 1403455
TI  - BUN/Cr ratio as an index of gastrointestinal bleeding mass in children.
AB  - Determining the site and severity of blood loss is important in the management of
      children with gastrointestinal (GI) bleeding. Blood urea nitrogen (BUN) and serum
      creatinine (Cr) were measured on the day of hospitalization and the ratio of
      BUN/Cr was calculated in 11 children with 16 episodes of upper GI bleeding and 49
      with lower GI bleeding. There was a significant difference between the two GI
      bleeding groups with regard to BUN/Cr ratio (p less than 0.001). When the ratio
      was 30 or above, the specificity of upper GI bleeding was 98% with a sensitivity
      of 68.8%. A linear relationship was found between the BUN/Cr ratio and delta Hb
      (delta Hb = 0.08 x BUN/Cr +/- 0.8 g/dl) for bleeding originating from the upper
      GI tract. This study confirms that measurement of the BUN/Cr ratio is useful for
      localizing the source of bleeding to the upper GI tract and also demonstrates its
      usefulness as an estimation of the severity of blood loss from the upper GI
      tract.

PMID- 1403456
TI  - Eosinophilic infiltration of the esophageal muscle layer: a difficult diagnostic
      problem.

PMID- 1403457
TI  - Omental cyst: presentation in an infant with jaundice and increasing abdominal
      girth.

PMID- 1403458
TI  - Congenital sodium diarrhea with a partial defect in jejunal brush border membrane
      sodium transport, normal rectal transport, and resolving diarrhea.
AB  - Defective jejunal sodium/proton exchange causes severe, congenital secretory
      diarrhea. We report a boy who presented typically in utero, but in whom diarrhea
      resolved during the first year of life. Pregnancy was complicated by
      polyhydramnios, and an ultrasound at 31 weeks showed a distended fetal small
      intestine. The abdomen was grossly distended at birth, and profuse secretory
      diarrhea began immediately. He subsequently thrived on breast milk and
      electrolyte supplements. Studies of jejunal brush border sodium/proton exchange
      at 6 months showed a partial defect. Nonequilibrium rectal dialysis showed rectal
      sodium and potassium transport to be intact. Diarrhea lessened after 9 months,
      and the patient subsequently required occasional laxatives. These observations
      suggest that there is a spectrum of congenital abnormality in this exchanger, and
      that in children with incomplete defects normal colonic sodium salvage can
      subsequently mask net small intestinal secretion.

PMID- 1403459
TI  - Efficacy of massive dose oral gentamicin therapy in nonbloody persistent diarrhea
      with associated malnutrition.
AB  - Overgrowth of aerobic and anaerobic bacteria in the upper small intestine is a
      common finding in persistent diarrhea. We hypothesized that a large dose of broad
      spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent
      diarrhea by eradicating aerobic bacterial overgrowth. Sixty-eight patients were
      randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n
      = 35) for a period of 6 days. The two groups were comparable in their clinical
      features, stool weights, duodenal and fecal microflora, during an initial 24 h
      observation period before randomization. The proportion of patients recovering
      within 6 days post-treatment was similar in the antibiotic (45.2%) and placebo
      (50%) groups. The stool weights in the two groups during 24-72, 72-120, and 120
      168 h of the study did not differ significantly. The percent mean weight gain (g)
      at 168 h post-treatment in the antibiotic (1.0 +/- 5.1) and placebo (1.4 +/- 5.3)
      groups also did not differ significantly (p = 0.8). A similar proportion of
      antibiotic- (61.3%) and placebo- (60.7%) treated patients had started to gain
      weight by the last day of the study. We conclude that oral gentamicin was no more
      effective than placebo in reducing purge rates, in achieving earlier recovery
      from diarrhea, and in promoting the earlier onset of weight gain in this study.

PMID- 1403460
TI  - Cardiac, respiratory, and arousal responses to an esophageal acid infusion test
      in near-term infants during active sleep.
AB  - This study was designed to determine the cardiac, respiratory, and arousal
      responses to an esophageal acid infusion test in near-term infants free from
      neurological, gastroesophageal, and cardiopulmonary disease at time of testing
      during active sleep. Eight infants (gestational age 28-37.5 weeks,
      postconceptional age 36-40 weeks) were tested. Using standardized procedures and
      timing, we compared the cardiac, respiratory and arousal responses during a
      control period and during distal esophageal saline and acid infusion periods. The
      duration of each of these periods was 5 min. The pH of the acid infusion was 2.2.
      We found that this mild distal esophageal acid infusion test induced significant
      prolongation of the interval between successive electrocardiogram R waves
      compared with control and saline infusion periods (806.5 +/- 145.7 ms, 478.8 +/-
      49.4 ms, and 468.8 +/- 37.2 ms, respectively; p less than 0.01) and of the
      duration of the respiratory cycle (2.9 +/- 0.7 s, 1.5 +/- 0.3 s, and 1.5 +/- 0.2
      s, respectively; p less than 0.01). Esophageal acid infusion elicited significant
      electroencephalogram (EEG) arousal responses. The number of the EEG arousals was
      significantly increased during the acid period as compared with control and
      saline infusion periods (2.9 +/- 1.4, 0.5 +/- 0.5, and 0.4 +/- 0.5, respectively;
      p less than 0.01). Total arousal duration was significantly increased during acid
      as compared with control and saline infusion periods (42 +/- 17.5 s, 4.5 +/- 5.1
      s, and 3.5 +/- 5.0 s, respectively; p less than 0.01). We conclude that distal
      esophageal acid stimulation elicits significant cardiac, respiratory, and EEG
      arousal responses in near-term infants during active sleep.

PMID- 1403461
TI  - Nutritional rehabilitation in cystic fibrosis: a 5 year follow-up study.
AB  - Previously, we reported catch-up weight gain, growth, and improved lung function
      in a group of malnourished cystic fibrosis (CF) children receiving aggressive
      nutritional supplementation for 1 year compared with a forced expiratory volume
      in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard
      therapy. To evaluate long-term effects, the clinical progress of both groups has
      been studied over a 5 year period. The supplemented group (n = 10) received
      supplements for a median of 1.35 years to achieve nutritional rehabilitation.
      Compared with the nonsupplemented group (n = 14), the previously supplemented
      group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and
      height z scores at 4 and 5 years. The progression of pulmonary function
      abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was
      greater at 3 years in the nonsupplemented group (FEV1, p less than 0.05) but no
      significant differences in rates of deterioration of pulmonary function were seen
      after 5 years in the two groups of survivors. We conclude that intensive
      nutritional support for 1 year has both short- and long-term effects on nutrition
      and growth, still evident some years after the cessation of this therapeutic
      modality. Supplementation for periods of longer than 1 year may produce greater
      gains and possibly prolong the improvement in pulmonary function observed in the
      earlier study.

PMID- 1403462
TI  - Short-chain fatty acid absorption in patients with cystic fibrosis.
AB  - Patients with cystic fibrosis (CF) often exhibit malabsorption despite the use of
      supplemental pancreatic enzymes. Unabsorbed carbohydrates and amino acids can
      serve as substrates for large intestine anaerobic fermentation, thus increasing
      excretion of short-chain fatty acids (SCFA) in the feces. Nine patients with CF
      on regular pancreatic enzyme supplementations in the age range of 5-11 years and
      one older patient were studied. Three-day stool samples were collected, as were
      72-h food records. Stools were analyzed for gross energy, total nitrogen, fat
      content, and SCFA concentration. A significant difference was found between CF
      and normal controls in total caloric excretion due to fat malabsorption. No
      significant difference was found between CF and normal controls in protein or
      SCFA excretion. Fat excretion as percentage of fat intake was significantly
      increased in CF patients: 35.3 +/- 10.2% versus 8.0 +/- 3.0%, respectively. These
      data suggest that carbohydrate supplementation could be more widely used to
      increase caloric intake in CF patients without causing secondary osmotic
      diarrhea.

PMID- 1403463
TI  - Gliadin-specific and cow's milk protein-specific IgA in human milk.
AB  - The presence of gliadin-specific IgA and IgG antibodies in colostrum and serum of
      140 newly delivered mothers was assessed by enzyme-linked immunosorbent assay. In
      addition, cow's milk protein (CMP)-specific IgA was determined in the colostrum
      samples. From 14 of the mothers longitudinal milk samples were obtained after 1
      and 2 months of lactation and from 12 mothers after 3 months. Gliadin-specific
      IgA was found in 97.1% and gliadin-specific IgG in 9.3% of the colostrum samples.
      Gliadin-specific IgA was detected in mature samples but at significantly lower
      levels after 1, 2, and 3 months of lactation (p less than 0.01) as compared with
      colostrum. Gliadin-specific IgA was found in 2.8% of the serum samples and
      gliadin-specific IgG in 40%; however, the levels of both isotypes were low. CMP
      specific IgA was found in 78.1% of the colostrum samples. It is concluded that
      IgA antibodies to two common food proteins are frequently found in human milk and
      that food-specific IgA present in milk may play a role in adapting the infant's
      immune reactions to food antigens in the gut.

PMID- 1403464
TI  - Gastrointestinal priming prior to full enteral nutrition in very low birth weight
      infants.
AB  - Priming of the gastrointestinal (GI) tract with low-volume feedings before giving
      full enteral feedings to very premature, high-risk infants is a controversial
      practice. We designed a study of infants weighing less than 1,250 g and receiving
      total parenteral nutrition to determine whether GI priming would hasten weight
      gain, improve tolerance of subsequent feedings, enhance nutritional status, and
      increase serum concentration of gastrin, a hormone trophic for intestinal growth.
      Infants were randomly assigned to receive total parenteral nutrition (TPN) alone
      (N = 21) or GI priming plus TPN (N = 19) for 12 days beginning on day 3 of life.
      Full-strength premature infant formula was used for priming. Both groups received
      the same total nutrition. Beginning on day 15, feedings in both groups were
      increased daily to a maximum of 120 kcal/kg/day on day 20, where they were
      maintained until day 30. After day 30, the feedings were modified according to
      the infants' condition. The groups did not differ in birth weight, gestational
      age, or 5-min Apgar scores. GI-primed infants had improved feeding tolerance
      after day 20 and a faster rise in serum gastrin during the initial phase of the
      study. There was no significant difference in weight gain. GI priming improves
      tolerance of feedings, accelerates rate of rise of serum gastrin during the first
      weeks of life, and does not increase the risk of feeding complications when
      compared to TPN alone. This may lead to more rapid maturation of the GI tract in
      primed infants.

PMID- 1403465
TI  - Hypoxemia in infants with biliary atresia: the role of airway obstruction.
AB  - Hypoxemia in liver cirrhosis has been attributed to increased pulmonary
      perfusion; lung function abnormalities have rarely been found in adults. In
      infants, however, smaller airways and the disproportion in size between the
      enlarged liver and abdominal cavity leading to lung compression by elevated
      diaphragms may well suggest that ventilation disturbances play an important role
      in the development of hypoxemia. We examined lung functions, ventilation
      perfusion scans, chest radiographs, and blood gases in air and 80% oxygen in 19
      infants with biliary atresia (mean age 14 months) and found maximum flows at
      functional residual capacity (VmaxFRC) markedly decreased [48% +/- 29% (mean +/-
      SD)] and thoracic gas volume (TGV) elevated (156% +/- 30.2%). PO2 was less than
      9.3 kPa in seven of 19 patients, in whom TGV was higher compared with the other
      patients (182% vs. 141%, p less than 0.005). However, the decrease in PO2, was
      much more closely correlated to the amount of shunting (r = 0.62, p less than
      0.05) than to the reduced airway patency (VmaxFRC/TGV, r = 0.41, p = 0.08). We
      conclude that airway narrowing probably by lung compression is present more
      frequently in infants than in adults with liver disease. We found some evidence
      that hyperinflation contributes to the observed low PO2 values, possibly
      aggravated by inadequate vasoconstriction to hypoxic stimuli. However, pulmonary
      shunting independent of ventilatory disturbances more readily explained hypoxemia
      already present in these infants.

PMID- 1403467
TI  - Chylous ascites following a Nissen fundoplication.

PMID- 1403466
TI  - Mixed hemangioma and cystic lymphangioma of the esophagus in a child.

PMID- 1403468
TI  - Effectiveness and pharmacokinetics of omeprazole in children with refractory
      duodenal ulcer.

PMID- 1403469
TI  - Hodgkin's disease presenting with fulminant liver disease.

PMID- 1403471
TI  - Successful orthotopic liver transplantation in two patients with liver failure
      due to sclerosing cholangitis with Langerhans cell histiocytosis.

PMID- 1403470
TI  - Fulminant hepatic failure in a child with acute lymphoblastic leukemia.

PMID- 1403472
TI  - Fibrosing pancreatitis associated with pericholangitis and cholangitis in a
      child.

PMID- 1403473
TI  - The puzzle of acute pancreatitis.

PMID- 1403474
TI  - Characterization of EPEC adhesion.

PMID- 1403475
TI  - Developmental regulation of the brush border hydrolase lactase.

PMID- 1403476
TI  - Gamma/delta T cells in celiac disease: friend or foe?

PMID- 1403477
TI  - Hepatocyte differentiation takes it in the LIP.

PMID- 1403479
TI  - Crown-rump length and pH probe length.

PMID- 1403478
TI  - Direct bilirubin measurements in term newborns--a waste of time and money?